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Neuphoria Therapeutics Inc.

Neuphoria Therapeutics Inc.NEUP決算レポート

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Neuphoria Therapeutics Inc is a clinical-stage biopharmaceutical company focused on researching and developing innovative targeted therapies for unmet medical needs in neurological and psychiatric conditions, including anxiety, treatment-resistant depression, and other central nervous system disorders. Its core R&D efforts prioritize delivering safer, more effective treatment options for patient groups with limited existing care alternatives.

What changed in Neuphoria Therapeutics Inc.'s 10-K — 2024 vs 2025

Top changes in Neuphoria Therapeutics Inc.'s 2025 10-K

540 paragraphs added · 648 removed · 427 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

198 edited+55 added−55 removed225 unchanged
Based on extensive preclinical data and clinical trials, we believe BNC210 may have a number of advantages over drugs currently used to treat anxiety, depression and PTSD, including: ● fast acting anxiolytic with the potential to be used in both acute and chronic settings; 2 ● non-sedating; ● no addictive effect and a lack of discontinuation/withdrawal syndrome; ● no memory impairment; ● no impairment of motor coordination; and ● no suicidality liability.
Based on extensive preclinical data and clinical trials, we believe BNC210 may have a number of advantages over drugs currently used to treat anxiety, depression and PTSD, including: • Fast acting anxiolytic with the potential to be used in both acute and chronic settings; • non-sedating; 2 • no addictive effect and a lack of discontinuation/withdrawal syndrome; • no memory impairment; • no impairment of motor coordination; and • no suicidality liability.
In September 2023, we announced the results of the Phase 2b ATTUNE study which was a double-blind, placebo-controlled trial conducted in a total of 34 sites in the United States and the United Kingdom, with 212 enrolled patients, randomized 1:1 to receive either twice daily 900 mg BNC210 as a monotherapy (n=106) or placebo (n=106) for 12 weeks.
In September 2023, we announced the results of the Phase 2b ATTUNE study which was a double-blind, placebo-controlled trial conducted in a total of 34 sites in the United States and the United Kingdom, with 212 enrolled patients, randomized 1:1 to receive either twice daily 900 mg BNC210 as a monotherapy (n=106) or placebo (n=106) for 12 weeks.
The trial met its primary endpoint of change in CAPS-5 total symptom severity score from baseline to Week 12 (p=0.048). A statistically significant change in CAPS-5 score was also observed at Week 4 (p=0.016) and at Week 8 (p=0.015).
The trial met its primary endpoint of change in CAPS-5 total symptom severity score from baseline to Week 12 (p=0.048). A statistically significant change in CAPS-5 score was also observed at Week 4 (p=0.016) and at Week 8 (p=0.015).
Treatment with BNC210 also showed statistically significant improvement both in clinician-administered and patient self-reporting in two of the secondary endpoints of the trial. Specifically, BNC210 led to significant improvements at Week 12 in depressive symptoms (p=0.041) and sleep (p=0.039) as measured by MADRS and ISI, respectively.
Treatment with BNC210 also showed statistically significant improvement both in clinician-administered and patient self-reporting in two of the secondary endpoints of the trial. Specifically, BNC210 led to significant improvements at Week 12 in depressive symptoms (p=0.041) and sleep (p=0.039) as measured by MADRS and ISI, respectively.
BNC210 also showed signals and trends across visits in the other secondary endpoints including the CGI-S, PGI-S and SDS.
BNC210 also showed signals and trends across visits in the other secondary endpoints including the CGI-S, PGI-S and the SDS.
Treatment with BNC210 also showed statistically significant improvement both in clinician-administered and patient self-reporting in two of the secondary endpoints of the trial. Specifically, BNC210 led to significant improvements at Week 12 in depressive symptoms (p=0.041) and sleep (p=0.039) as measured by MADRS and ISI, respectively.
Treatment with BNC210 also showed statistically significant improvement both in clinician-administered and patient self-reporting in two of the secondary endpoints of the trial. Specifically, BNC210 led to significant improvements at Week 12 in depressive symptoms (p=0.041) and sleep (p=0.039) as measured by MADRS and ISI, respectively.
While not FDA approved for PTSD or SAD, benzodiazepines may be prescribed off-label along with approved medications such as SSRIs/SNRIs. In addition to their distinctive sedative effects, benzodiazepines have other significant safety risks, including memory and motor impairment, serious risk of abuse, addiction, physical dependence, and withdrawal reactions, as highlighted in the FDA’s Drug Safety Communication in September 2020.
While not FDA approved for SAD or PTSD, benzodiazepines may be prescribed off-label along with approved medications such as SSRIs/SNRIs. In addition to their distinctive sedative effects, benzodiazepines have other significant safety risks, including memory and motor impairment, serious risk of abuse, addiction, physical dependence, and withdrawal reactions, as highlighted in the FDA’s Drug Safety Communication in September 2020.
Pursuant to the Carina Biotech License, we granted Carina Biotech an exclusive, worldwide license, with the right to grant sublicenses (subject to certain restrictions), under certain of our patents and know-how to research, develop, make, have made, use, sell, offer for sale, supply, cause to be supplied, import and otherwise exploit products applying the licensed patents and/or licensed know-how for research, commercial and development applications, and related fields, with respect to CAR-T cells, adaptor CARs and other adoptive cell therapies.
Pursuant to the Carina Biotech License, we granted Carina an exclusive, worldwide license, with the right to grant sublicenses (subject to certain restrictions), under certain of our patents and know-how to research, develop, make, have made, use, sell, offer for sale, supply, cause to be supplied, import and otherwise exploit products applying the licensed patents and/or licensed know-how for research, commercial and development applications, and related fields, with respect to CAR-T cells, adaptor CARs and other adoptive cell therapies.
The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of share-based compensation awards and cash-based performance bonus awards. Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.
Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees. The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of share-based compensation awards and cash-based performance bonus awards.
While PREVAIL narrowly missed its primary endpoint, as measured by the change from baseline to the average of the SUDS scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the December 2022 topline data readout revealed encouraging trends in the prespecified endpoints that focused on individual phases of the public speaking task (although these results are not predictive of future success or similar results).
While PREVAIL missed its primary endpoint, as measured by the change from baseline to the average of the SUDS scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the December 2022 topline data readout revealed encouraging trends in the prespecified endpoints that focused on individual phases of the public speaking task (although these results are not predictive of future success or similar results).
The FD&C Act requires that a sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (“PSP”), within 60 days of an End-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 trial.
The FD&C Act requires that a sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (“PSP”), within 60 days of an End-of-Phase 2 meeting or, if there is no such 32 meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 trial.
Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA.
Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe, in their 33 independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA.
In September 2023, we announced the results of the Phase 2b ATTUNE study which was a double-blind, placebo-controlled trial conducted in a total of 34 sites in the United States and the United Kingdom, with 212 enrolled patients, randomized 1:1 to receive either twice daily 900 mg BNC210 as a monotherapy (n=106) or placebo (n=106) for 12 weeks.
In September 2023, we announced the results of the Phase 2b ATTUNE trial, which was a double-blind, placebo-controlled trial conducted in a total of 34 sites in the United States and the United Kingdom, with 212 enrolled patients, randomized 1:1 to receive either twice daily 900 mg BNC210 as a monotherapy (n=106) or placebo (n=106) for 12 weeks.
Due to the specific requirements for obtaining these adjustments and extensions, there is no assurance that our patents will be afforded adjustments or extensions even if we encounter significant delays in patent office proceedings or marketing and regulatory approval. Inflation and Seasonality Management believes inflation has not had a material impact on our operations or financial condition.
Due to the specific requirements for obtaining these adjustments and extensions, there is no assurance that our patents will be afforded adjustments or extensions even if we encounter significant delays in patent office proceedings or marketing and regulatory approval. 27 Inflation and Seasonality Management believes inflation has not had a material impact on our operations or financial condition.
According to the Anxiety and Depression Association of America, 36% of people with SAD report experiencing symptoms for ten or more years before seeking help. Based on the early age of onset of SAD and the shortcomings of currently approved therapeutics, we believe SAD is underdiagnosed and the size of the potential patient population could be considerably underestimated.
According to the Anxiety and Depression Association of America, 36% of people with SAD report experiencing symptoms for ten or more years before 10 seeking help. Based on the early age of onset of SAD and the shortcomings of currently approved therapeutics, we believe SAD is underdiagnosed and the size of the potential patient population could be considerably underestimated.
The process of obtaining regulatory approvals of drugs and ensuring subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources. 34 In the United States, the FDA regulates drug products under the Federal Food, Drug, and Cosmetic Act (“FD&C Act”), as amended, its implementing regulations and other laws.
The process of obtaining regulatory approvals of drugs and ensuring subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources. In the United States, the FDA regulates drug products under the Federal Food, Drug, and Cosmetic Act (“FD&C Act”), as amended, its implementing regulations and other laws.
Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA. ● Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the approved indication.
Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA. 29 • Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the approved indication.
Background and Rationale on Targeting Ion Channels for CNS Disorders Overview of Ion Channels as a Drug Class Ion channels facilitate the movement of charged molecules across cellular membranes and are responsible for electrical signaling, serving as important mediators of physiological functions in the CNS. Modulation of ion channels influences neurotransmission that leads to downstream signaling in the brain.
Background and Rationale on Targeting Ion Channels for CNS Disorders Overview of Ion Channels as a Drug Class Ion channels facilitate the movement of charged molecules across cellular membranes and are responsible for electrical signaling, serving as important mediators of physiological functions in the CNS. Modulation of ion channels influences neurotransmission that 6 leads to downstream signaling in the brain.
In preclinical studies, BNC101 has shown good potential for the treatment of gastrointestinal tumors in combination with an antibody drug conjugate or CAR-T therapy. In November 2020, we exclusively licensed BNC101 to Carina Biotech for the development of CAR-T therapeutics, in return for milestones and royalties or a percentage of the out-licensed revenues.
In preclinical studies, BNC101 has shown good potential for the treatment of gastrointestinal tumors in combination with an antibody drug conjugate or CAR-T therapy. In November 2020, we exclusively licensed BNC101 to Carina for the development of CAR-T therapeutics, in return for milestones and royalties or a percentage of the out-licensed revenues.
With regard to our BNC210 product candidate, we own: ● one patent family with claims directed to the compositions of matter of BNC210, methods of preparing BNC210, and methods of treating anxiety and depressive disorders using BNC210, which are expected to expire in, 2027, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes patents granted in the U.S. as well as Australia, Canada, France, Germany, the United Kingdom, and Japan. 32 ● one patent family with claims directed to the manufacture and method of preparing BNC210, which are expected to expire in 2032, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes patents granted in the U.S. as well as Australia, Canada, the United Kingdom, Germany, and Japan; ● one patent family with claims directed to the crystalline form of BNC210, which are expected to expire in 2033, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes patents granted in the U.S. as well as Australia, Canada, the United Kingdom, Germany, France, Mexico, New Zealand and Hong Kong; ● one patent family with claims directed to the salts, cocrystal and polymorphic form of BNC210, which are expected to expire in 2034, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes granted patents in the U.S. and Australia; ● one patent family with claims directed to solid form formulations of BNC210.
With regard to our BNC210 product candidate, we own: • one patent family with claims directed to the compositions of matter of BNC210, methods of preparing BNC210, and methods of treating anxiety and depressive disorders using BNC210, which are expected to expire in, 2027, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes patents granted in the U.S. as well as Australia, Canada, France, Germany, the United Kingdom, and Japan. • one patent family with claims directed to the manufacture and method of preparing BNC210, which are expected to expire in 2032, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes patents granted in the U.S. as well as Australia, Canada, the United Kingdom, Germany, and Japan; • one patent family with claims directed to the crystalline form of BNC210, which are expected to expire in 2033, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes patents granted in the U.S. as well as Australia, Canada, the United Kingdom, Germany, France, Mexico, New Zealand and Hong Kong; 26 • one patent family with claims directed to the salts, cocrystal and polymorphic form of BNC210, which are expected to expire in 2034, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes granted patents in the U.S. and Australia; • one patent family with claims directed to solid form formulations of BNC210.
On October 11, Bionomics received the official meeting minutes from the End-of-Phase 2 meeting with the FDA held on September 13, 2023 reflecting that Bionomics has reached an agreement with the FDA on 1) the plan to conduct two single dose randomized, placebo-controlled studies; 2) the use of the SUDS measured during a public speaking challenge as the primary efficacy endpoint; 3) the doses of BNC210 to be studied in Phase 3; 4) the sample size assumptions for the Phase 3 controlled studies based on PREVAIL findings; 5) the design elements of the open label safety study; 6) the size of the safety database to support the NDA; and 7) the nonclinical toxicology studies needed to support the NDA.
On October 11, the Company received the official meeting minutes from the End-of-Phase 2 meeting with the FDA held on September 13, 2023 reflecting that the Company has reached an agreement with the FDA on 1) the plan to conduct two single dose randomized, placebo-controlled studies; 2) the use of the SUDS measured during a public speaking challenge as the primary efficacy endpoint; 3) the doses of BNC210 to be studied in Phase 3; 4) the sample size assumptions for the Phase 3 controlled studies based on PREVAIL findings; 5) the design elements of the open label safety study; 6) the size of the safety database to support the NDA; and 7) the nonclinical toxicology studies needed to support the NDA.
In addition, we utilize robust pharmacokinetic and pharmacometrics exposure-response relationship modeling in our translational and Phase 2 clinical trials to assess the target blood exposure and define the doses of the drug to be evaluated in our clinical trials, which we believe will result in an increased probability of success in the clinic.
In addition, we utilize robust pharmacokinetic and pharmacometrics exposure-response 8 relationship modeling in our translational and Phase 2 clinical trials to assess the target blood exposure and define the doses of the drug to be evaluated in our clinical trials, which we believe will result in an increased probability of success in the clinic.
The FDA may also require one or more post-approval studies and surveillance, including Phase 4 clinical trials, be conducted to further assess and monitor the product’s safety and effectiveness after marketing, and may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
The FDA may also require one or more post-approval 31 studies and surveillance, including Phase 4 clinical trials, be conducted to further assess and monitor the product’s safety and effectiveness after marketing, and may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
In October 2023, Bionomics received the official meeting minutes from the End-of-Phase 2 meeting with the FDA held on September 13, 2023 reflecting that Bionomics has reached an agreement with the FDA on the following: ● the plan to conduct two single dose randomized, placebo-controlled studies; ● the use of the SUDS measured during a public speaking challenge as the primary efficacy endpoint; ● the doses of BNC210 to be studied in Phase 3; ● the sample size assumptions for the Phase 3 controlled studies based on PREVAIL findings; ● the design elements of the open label safety study; ● the size of the safety database to support the NDA; and ● the nonclinical toxicology studies needed to support the NDA.
In October 2023, the Company received the official meeting minutes from the End-of-Phase 2 meeting with the FDA held on September 13, 2023 reflecting that the Company has reached an agreement with the FDA on the following: • the plan to conduct two single dose randomized, placebo-controlled studies; • the use of the SUDS measured during a public speaking challenge as the primary efficacy endpoint; • the doses of BNC210 to be studied in Phase 3; • the sample size assumptions for the Phase 3 controlled studies based on PREVAIL findings; • the design elements of the open label safety study; • the size of the safety database to support the NDA; and • the nonclinical toxicology studies needed to support the NDA.
The trial met its primary endpoint of change in CAPS-5 total symptom severity score from baseline to Week 12 (p=0.048). A statistically significant change in CAPS-5 score was also observed at Week 4 (p=0.016) and at Week 8 (p=0.015).
The trial met its primary endpoint of 3 change in CAPS-5 total symptom severity score from baseline to Week 12 (p=0.048). A statistically significant change in CAPS-5 score was also observed at Week 4 (p=0.016) and at Week 8 (p=0.015).
In certain instances, such as with accelerated approval drugs, FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA. 36 During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points.
In certain instances, such as with accelerated approval drugs, FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA. During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points.
Under the collaboration, BNC375 was further characterized showing that it enhanced long-term potentiation of electrically evoked synaptic responses in rat hippocampal slices and in vivo , which is an established preclinical surrogate for memory enhancement.
Under the collaboration, BNC375 was further characterized showing that it enhanced long-term 22 potentiation of electrically evoked synaptic responses in rat hippocampal slices and in vivo , which is an established preclinical surrogate for memory enhancement.
Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution. 41 Marketing Exclusivity Market exclusivity provisions under the FD&C Act can delay the submission or the approval of certain marketing applications.
Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution. Marketing Exclusivity Market exclusivity provisions under the FD&C Act can delay the submission or the approval of certain marketing applications.
With regard to our BNC101 product candidate, we own six patent families with claims directed to compositions of matter and various methods of treatment using BNC101, with granted patents in the U.S., Australia, France, Germany, Japan, China, India, Korea, New Zealand and Hong Kong, with expiration dates ranging from 2033 to 2039, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable.
With regard to our BNC101 product candidate, we own three patent families with claims directed to compositions of matter and various methods of treatment using BNC101, with granted patents in the U.S., Australia, France, Germany, Japan, China, India, Korea, New Zealand and Hong Kong, with expiration dates ranging from 2033 to 2039, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable.
Participants are then required to give a 5-minute speech in front of a small audience (performance phase). The primary endpoint of the trial is the change from baseline to the average of the performance phase of the public speaking challenge in SUDS scores.
Participants are then required to give a 5-minute speech in front of a small audience (performance phase). 19 The primary endpoint of the trial is the change from baseline to the average of the performance phase of the public speaking challenge in SUDS scores.
Under the Carina Biotech License, Carina Biotech is obligated to use commercially reasonable efforts to commercially develop and exploit licensed products in each country in which Carina Biotech obtains regulatory approval for the licensed products. Carina Biotech is responsible for conducting all regulatory activities for the licensed products.
Under the Carina Biotech License, Carina is obligated to use commercially reasonable efforts to commercially develop and exploit licensed products in each country in which Carina obtains regulatory approval for the licensed products. Carina is responsible for 25 conducting all regulatory activities for the licensed products.
BNC210 also showed signals and trends across visits in the other secondary endpoints including the clinician and patient global impression - symptom severity (“CGI-S”, “PGI-S”, respectively) and the Sheehan Disability Scale (“SDS”).
BNC210 also showed signals and trends across visits in the other secondary endpoints including the clinician and patient global impression - symptom severity (“CGI-S”, “PGI-S”, respectively) scales and the Sheehan Disability Scale (“SDS”).
Furthermore, emerging evidence indicates that benzodiazepines may inhibit brain areas involved in fear learning, including the amygdala, further delaying recovery and counteracting the effects of the treatment. 12 ● Beta Blockers .
Furthermore, emerging evidence indicates that benzodiazepines may inhibit brain areas involved in fear learning, including the amygdala, further delaying recovery and counteracting the effects of the treatment. • Beta Blockers .
While PREVAIL narrowly missed its primary endpoint, as measured by the change from baseline to the average of the SUDS scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the December 2022 topline data readout revealed encouraging trends in the prespecified endpoints that focused on individual phases of the public speaking task.
Action of BNC210 While PREVAIL missed its primary endpoint, as measured by the change from baseline to the average of the SUDS scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the December 2022 topline data readout revealed encouraging trends in the prespecified endpoints that focused on individual phases of the public speaking task.
As such, we are dependent on MSD to provide us with any updates related to clinical trial results, serious adverse events and ongoing communications with FDA or other regulatory agencies related to these programs, which MSD may provide or withhold in its sole discretion, and as a result we may not be able to provide material updates on a timely basis or at all with respect to these programs.
As such, we are dependent on Merck to provide us with any updates related to clinical trial results, serious adverse events and ongoing communications with FDA or other regulatory agencies related to these programs, which Merck may provide or withhold in its sole discretion, and as a result we may not be able to provide material updates on a timely basis or at all with respect to these programs.
Bionomics is initially seeking to treat conditions of hypercholinergic and hypocholinergic disease states using therapeutics that restore homeostasis. 7 α7 Nicotinic Acetylcholine Receptor as a Target The α7 receptor is a member of the cys-loop, ligand-gated, ion channel superfamily, which includes several other nicotinic receptor subtypes as well as GABA-A, glycine and 5-HT3 receptors.
Neuphoria is initially seeking to treat conditions of hypercholinergic and hypocholinergic disease states using therapeutics that restore homeostasis. α7 Nicotinic Acetylcholine Receptor as a Target The α7 receptor is a member of the cys-loop, ligand-gated, ion channel superfamily, which includes several other nicotinic receptor subtypes as well as GABA-A, glycine and 5-HT3 receptors.
Liquid Suspension Formulation Tablet Formulation We carried out a second Phase 1 single ascending dose pharmacokinetic clinical trial in five healthy subjects in which each subject, in a fasted state, was dosed with 600 mg, 900 mg, and 1200 mg of BNC210 tablet formulation with a wash-out period of at least five days between treatments.
We carried out a second Phase 1 single ascending dose pharmacokinetic clinical trial in five healthy subjects in which each subject, in a fasted state, was dosed with 600 mg, 900 mg, and 1200 mg of BNC210 tablet formulation with a wash-out period of at least five days between treatments.
The trial met its primary endpoint of change in CAPS-5 total symptom severity score from baseline to Week 12 (p=0.048). A statistically significant change in CAPS-5 score was also observed at Week 4 (p=0.016) and at Week 8 (p=0.015) (Figure 14).
The trial met its primary endpoint of change in CAPS-5 total symptom severity score from baseline to Week 12 (p=0.048). A statistically significant change in CAPS-5 score was also observed at Week 4 (p=0.016) and at Week 8 (p=0.015) (Figure 15).
There have been two serious adverse events (“SAEs”) that were deemed by the investigators to be at least possibly related to BNC210: one SAE reported for hypotension (with alternative causality of dehydration) for an elderly patient was deemed possibly related to study drug by the independent investigator, however, after a saline infusion, blood pressure returned to within normal limits within 45 minutes and the subject continued on the study; and one SAE for elevated liver function tests reported 14 days after last treatment dose for a PTSD subject who remained asymptomatic throughout the study and in follow up was deemed probably related to study drug by the independent investigator.
There have been two serious adverse events (“SAEs”) that were deemed by the investigators to be at least possibly related to BNC210: one SAE reported for hypotension (with alternative causality of dehydration) for an elderly patient was deemed possibly related to study drug by the independent investigator, however, after a saline infusion, blood pressure returned to within normal limits within 45 minutes and the subject continued on the study; and one SAE for elevated LFTs reported 14 days after last treatment dose for a PTSD subject who remained asymptomatic throughout the study and in follow up was deemed probably related to study drug by the independent investigator.
These conventional orthosteric α7 receptor agonists have suffered from off-target activity, receptor desensitization, and a narrow therapeutic window that have limited their clinical utility. Allosteric modulators of the α7 receptor bind at the transmembrane region (see Figure 1) at sites distinct from the orthosteric sites.
These conventional orthosteric α7 receptor agonists have suffered from off-target activity, receptor desensitization, and a narrow therapeutic window that have limited their clinical utility. Allosteric modulators of the α7 receptor bind at the transmembrane region (see Figure 3) at sites distinct from the orthosteric sites.
The patent and patent applications claiming priority to this PCT application, if issued, are expected to expire in 2040, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes a patent granted in China, as well as multiple patent applications currently pending in the United States, Canada, China, Europe, Japan, Korea, Mexico, New Zealand, Israel and Australia; and ● two provisional applications filed with claims directed toward methods of treating social anxiety disorder and post trauma stress disorder.
The patent and patent applications claiming priority to this PCT application, if issued, are expected to expire in 2040, excluding any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, as applicable; this family includes a patent granted in China and a patent granted in the U.S., as well as multiple patent applications currently pending in Canada, China, Europe, Japan, Korea, Mexico, New Zealand, Israel and Australia; and • two provisional applications filed with claims directed toward methods of treating social anxiety disorder and post trauma stress disorder.
BNC210 demonstrated statistically significant reduction in both the number and intensity of panic symptoms on the Panic Symptoms Scale (“PSS”) compared to placebo 10 minutes after the CCK-4 injection, as seen in the figure below (p=0.048 and p=0.041, respectively).
BNC210 demonstrated statistically significant reduction in both the intensity and number of panic symptoms on the Panic Symptoms Scale (“PSS”) compared to placebo 10 minutes after the CCK-4 injection, as seen in Figure 7 (p=0.041 and p=0.048, respectively).
In June 2014, we entered into a strategic collaboration with MSD to develop novel PAMs, including our BNC375 research program, for the treatment of cognitive dysfunction associated with Alzheimer’s disease and other central nervous system conditions.
In June 2014, we entered into a strategic collaboration with Merck to develop novel PAMs, including our BNC375 research program, for the treatment of cognitive dysfunction associated with Alzheimer’s disease and other central nervous system conditions.
DEA may adjust aggregate production quotas and individual production and procurement quotas from time to time during the year, although DEA has substantial discretion in whether or not to make such adjustments. Individual states also regulate controlled substances. 37 U.S.
DEA may adjust aggregate production quotas and individual production and procurement quotas from time to time during the year, although DEA has substantial discretion in whether or not to make such adjustments. Individual states also regulate controlled substances. 30 U.S.
In July 2024, we announced the initiation of patient screening for the Phase 3 AFFIRM-1 trial evaluating the safety and efficacy of BNC210 for the acute, as-needed treatment of SAD. AFFIRM-1 targets enrollment of 330 adult patients with SAD at clinical sites in the United States. It is a multi-center, double-blind, two-arm, parallel group, placebo-controlled trial.
In July 2024, we announced the initiation of patient screening for the Phase 3 AFFIRM-1 trial evaluating the safety and efficacy of BNC210 for the acute, as-needed treatment of SAD. AFFIRM-1 targets enrollment of approximately 332 adult patients with SAD at clinical sites in the United States. It is a multi-center, double-blind, two-arm, parallel group, placebo-controlled trial.
In July 2024, we announced the initiation of patient screening for the Phase 3 AFFIRM-1 trial evaluating the safety and efficacy of BNC210 for the acute, as-needed treatment of SAD. AFFIRM-1 targets enrollment of 330 adult patients with SAD at clinical sites in the United States. It is a multi-center, double-blind, two-arm, parallel group, placebo-controlled trial.
In July 2024, we announced the initiation of patient screening for the Phase 3 AFFIRM-1 trial evaluating the safety and efficacy of BNC210 for the acute, as-needed treatment of SAD. AFFIRM-1 targets enrollment of approximately 332 adult patients with SAD at clinical sites in the United States. It is a multi-center, double-blind, two-arm, parallel group, placebo-controlled trial.
Cancer stem cells are the seeds that give rise to initial tumor formation and if left unchecked, give rise to tumor recurrence and metastasis. Our first legacy oncology program is BNC101, a novel humanized monoclonal antibody that targets LGR5, a cancer stem cell receptor highly overexpressed in most solid tumors, including colorectal, breast, pancreatic, ovarian, lung, liver and skin cancers.
Cancer stem cells are the seeds that give rise to initial tumor formation and if left unchecked, give rise to tumor recurrence and metastasis. Our first legacy oncology program is BNC101, a novel humanized monoclonal antibody that targets LGR5, a cancer stem cell receptor highly over-expressed in most solid tumors, including colorectal, breast, pancreatic, ovarian, lung, liver and skin cancers.
MSD controls the clinical development and worldwide commercialization of any products developed from the collaboration and therefore we cannot predict whether or when we might achieve any milestone payments under the collaboration or estimate the full amount of such payments, and we may never receive any such payments.
Merck controls the clinical development and worldwide commercialization of any products developed from the collaboration and therefore we cannot predict whether or when we might achieve any milestone payments under the collaboration or estimate the full amount of such payments, and we may never receive any such payments.
While PREVAIL narrowly missed its primary endpoint, as measured by the change from baseline to the average of the SUDS scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the December 2022 topline data readout revealed encouraging trends in the prespecified endpoints that focused on individual phases of the public speaking task.
While PREVAIL narrowly missed its primary endpoint, as measured by the change from baseline to the average of the SUDS scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the data readout revealed encouraging trends in the prespecified endpoints that focused on individual phases of the public speaking task.
BNC210 300 mg also statistically significantly reduced connectivity between the amygdala and the anterior cingulate cortex (“ACC”), a network involved in regulating anxious responses to aversive stimuli (p=0.012) (Figure 7).
BNC210 300 mg also statistically significantly reduced connectivity between the amygdala and the anterior cingulate cortex (“ACC”), a network involved in regulating anxious responses to aversive stimuli (p=0.012) (Figure 8B).
BNC210’s psychoactive profile, its favorable safety and tolerability and pharmacokinetic properties make it an ideal candidate for both chronic and acute treatment across a number of neuropsychiatric diseases including PTSD and SAD.
BNC210’s psychoactive profile, its favorable safety and tolerability and pharmacokinetic properties make it an ideal candidate for both acute and chronic treatment across a number of neuropsychiatric diseases including SAD and PTSD. Figure 4.
We are obligated to assist Carina Biotech as reasonably requested from time to time in connection with its regulatory filings. We are also obligated to provide technology transfer to Carina Biotech, at Carina Biotech’s request, of know-how and technical information that is useful or necessary for Carina Biotech to fully exercise the rights licensed to it under the agreement.
We are obligated to assist Carina as reasonably requested from time to time in connection with its regulatory filings. We are also obligated to provide technology transfer to Carina, at Carina’s request, of know-how and technical information that is useful or necessary for Carina to fully exercise the rights licensed to it under the agreement.
BNC210 Clinical Development in SAD We initiated an SAD trial, which we refer to as the PREVAIL Study, evaluating the effects of acute dosing of BNC210 on anxiety in SAD, using a standardized public speaking challenge.
BNC210 Clinical Development in SAD We conducted an SAD trial, which we refer to as the PREVAIL Study, evaluating the effects of acute dosing of BNC210 on anxiety in SAD, using a standardized Public Speaking Challenge.
In October 2023, Bionomics received the official meeting minutes from the End-of-Phase 2 meeting with the FDA held on September 13, 2023, reflecting that Bionomics has reached an agreement with the FDA on the following: ● the plan to conduct two single dose randomized, placebo-controlled studies; ● the use of the SUDS measured during a public speaking challenge as the primary efficacy endpoint; ● the doses of BNC210 to be studied in Phase 3; ● the sample size assumptions for the Phase 3 controlled studies based on PREVAIL findings; ● the design elements of the open label safety study; ● the size of the safety database to support the NDA; and ● the nonclinical toxicology studies needed to support the NDA.
In October 2023, the Company received the official meeting minutes from the End-of-Phase 2 meeting with the FDA, reflecting that the Company has reached an agreement with the FDA on the following: • the plan to conduct two single dose randomized, placebo-controlled studies; • the use of the SUDS measured during a public speaking challenge as the primary efficacy endpoint; • the doses of BNC210 to be studied in Phase 3; • the sample size assumptions for the Phase 3 controlled studies based on PREVAIL findings; • the design elements of the open label safety study; • the size of the safety database to support the NDA; and • the nonclinical toxicology studies needed to support the NDA.
Through the dynamic interaction between the molecules bound to each site, allosteric modulators serve to “normalize” function of the ion channel by mitigating hypercholinergic and hypocholinergic disease states (see Figure 2).
Through the dynamic interaction between the molecules bound to each site, allosteric modulators serve to “normalize” function of the ion channel by mitigating hypercholinergic and hypocholinergic disease states (see Figure 3).
Phase 1 Clinical Trial Demonstrating Target Engagement in Brain at Nicotinic Receptor in Healthy Subjects We conducted a Phase 1 clinical trial to demonstrate BNC210 target engagement at brain nicotinic receptors measured by EEG activity (see figure below).
Phase 1 Clinical Trial Demonstrating Target Engagement in Brain at Nicotinic Receptor in Healthy Subjects We conducted a Phase 1 clinical trial to demonstrate BNC210 target engagement at brain nicotinic receptors measured by EEG activity (see Figure 6).
The findings did indicate a consistent trend toward improvements across primary and secondary endpoints and a favorable safety and tolerability profile consistent with previously reported results. We also completed an FDA End-of-Phase 2 meeting to discuss the registrational program for BNC210 in SAD.
The 9 findings did indicate a consistent trend toward improvements across primary and secondary endpoints and a favorable safety and tolerability profile consistent with previously reported results. We recently completed an FDA End-of-Phase 2 meeting to discuss the registrational program for BNC210 in SAD.
If competitor companies develop technologies or drug candidates more rapidly than we do, or their technologies are more effective, our ability to develop and successfully commercialize drug candidates may be adversely affected. Our competitors may also obtain FDA, EMA, TGA or other regulatory approval for their products more rapidly than we may obtain approval for ours.
If competitor companies develop technologies or drug candidates more rapidly than we do, or their technologies are more effective, our ability to develop and successfully commercialize drug candidates may be adversely affected. Our competitors may also obtain FDA, EMA, Therapeutic Goods Administration ("TGA") or other regulatory approval for their products more rapidly than we may obtain approval for ours.
BNC210 300 mg, similarly to lorazepam, statistically significantly reduced amygdala reactivity to “fearful faces” relative to placebo (BNC210 300 mg left amygdala p=0.011; BNC210 300 mg right amygdala p=0.006; lorazepam right amygdala p=0.047) (Figure 6).
BNC210 300 mg, similarly to lorazepam, statistically significantly reduced amygdala reactivity to “fearful faces” relative to placebo (BNC210 300 mg left amygdala p=0.011; BNC210 300 mg right amygdala p=0.006; lorazepam right amygdala p=0.047) (Figure 8A).
In response to ACh, the opening and closing of the ion channel allows the preferential flow of Ca2+ into the cell, which governs neuronal function and neurotransmission, as seen in the figure below. 8 Figure 2: Structure of the α7 receptor showing the orthosteric and allosteric binding sites.
In response to ACh, the opening and closing of the ion channel allows the preferential flow of Ca2+ into the cell, which governs neuronal function and neurotransmission, as seen in the figure below. Figure 3: Structure of the α7 receptor showing the orthosteric and allosteric binding sites.
While PREVAIL narrowly missed its primary endpoint, as measured by the change from baseline to the average of the Subjective Units of Distress Scale (“SUDS”) scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the December 2022 topline data readout revealed encouraging trends in the prespecified endpoints.
While PREVAIL missed its primary endpoint, as measured by the change from baseline to the average of the Subjective Units of Distress Scale (“SUDS”) scores during a 5-minute Public Speaking Challenge in the BNC210-treated patients when compared to placebo, the data readout revealed encouraging trends in the prespecified endpoints.
Treatment with BNC210 also showed statistically significant improvement both in clinician-administered and patient self-reporting in two of the secondary endpoints of the trial. Specifically, BNC210 led to significant improvements at Week 12 in depressive symptoms (p=0.041) (Figure 15A) and sleep (p=0.039) (Figure 15B) as measured by MADRS and ISI respectively.
Treatment with BNC210 also showed statistically significant improvement both in clinician-administered and patient self-reporting in two of the secondary endpoints of the trial. Specifically, BNC210 led to significant improvements at Week 12 in depressive symptoms (p=0.041) (Figure 16A) and sleep (p=0.039) (Figure 16B) as measured by MADRS and ISI respectively.
When levels of ACh are elevated in critical regions of the brain, the result is a “hypercholinergic disease state”, whereas when levels of ACh are inadequate in critical regions of the brain, the result is a “hypocholinergic disease state” (Figure 1).
When levels of ACh are elevated in critical regions of the brain, the result is a “hypercholinergic disease state”, whereas when levels of ACh are inadequate in critical regions of the brain, the result is a “hypocholinergic disease state” (Figure 2).
In addition, several investigators and self-reported secondary efficacy endpoints related to CAPS-5 symptom cluster severity scores and anxiety and depression measures along with safety and tolerability endpoints were reported (Figure 13). 21 Figure 13: Phase 2b ATTUNE clinical trial design. In September 2023, we announced the results of the Phase 2b ATTUNE study.
In addition, several investigators and self-reported secondary efficacy endpoints 20 related to CAPS-5 symptom cluster severity scores and anxiety and depression measures along with safety and tolerability endpoints were reported (Figure 14). Figure 14: Phase 2b ATTUNE clinical trial design. In September 2023, we announced the results of the Phase 2b ATTUNE study.
The process required by the FDA before a drug may be marketed in the United States generally involves the following: ● completion of extensive preclinical laboratory tests, animal studies and formulation studies in accordance with good laboratory practice (“GLP”), requirements and other applicable regulations; ● submission to the FDA of an IND application, which must become effective before clinical trials may begin; ● approval by an IRB, or independent ethics committee at each clinical trial site before each trial may be initiated; ● performance of adequate and well-controlled clinical trials in accordance with applicable IND regulations, GCP, requirements and other regulations, to establish the safety and efficacy of the investigational product for its intended use; ● submission to the FDA of an NDA, after completion of all pivotal trials; ● a determination by the FDA within 60 days of its receipt of an NDA, to accept the filing for review; ● satisfactory completion of an FDA advisory committee review, if applicable; ● satisfactory completion of one or more FDA pre-approval inspections of the manufacturing facility or facilities where the drug will be produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; ● potential FDA audit of the clinical trial sites that generated the data in support of the NDA; ● payment of user fees for FDA review of the NDA; and ● FDA review and approval of the NDA to permit commercial marketing or sale of the drug for particular indications for use in the United States. 35 Preclinical Studies and Clinical Trials for Drugs Before testing any drug in humans, the product candidate must undergo rigorous preclinical testing.
The process required by the FDA before a drug may be marketed in the United States generally involves the following: • completion of extensive preclinical laboratory tests, animal studies and formulation studies in accordance with good laboratory practice (“GLP”), requirements and other applicable regulations; • submission to the FDA of an an Investigational New Drug Application (“IND”) application, which must become effective before clinical trials may begin; • approval by an Institutional Review Board (“IRB”) or independent ethics committee at each clinical trial site before each trial may be initiated; • performance of adequate and well-controlled clinical trials in accordance with applicable IND regulations, good clinical practice (“GCP”) requirements and other regulations, to establish the safety and efficacy of the investigational product for its intended use; • submission to the FDA of an NDA, after completion of all pivotal trials; • a determination by the FDA within 60 days of its receipt of an NDA, to accept the filing for review; • satisfactory completion of an FDA advisory committee review, if applicable; • satisfactory completion of one or more FDA pre-approval inspections of the manufacturing facility or facilities where the drug will be produced to assess compliance with current good manufacturing practice (“cGMP”) requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; • potential FDA audit of the clinical trial sites that generated the data in support of the NDA; • payment of user fees for FDA review of the NDA; and • FDA review and approval of the NDA to permit commercial marketing or sale of the drug for particular indications for use in the United States. 28 Preclinical Studies and Clinical Trials for Drugs Before testing any drug in humans, the product candidate must undergo rigorous preclinical testing.
For the SAE related to elevated liver function, it was subsequently noted in a safety report to the FDA that the Independent Safety Monitoring Board for the RESTORE study did not believe that this adverse event met the criterion for an SAE.
For the SAE related to elevated liver function, it was subsequently noted in a safety report to the FDA that the Independent Safety Monitoring Board for the study did not consider that this adverse event met the criterion for an SAE.
Based on the favorable rapid absorption profile of our novel tablet formulation and evidence of anti-anxiety effect from our prior Phase 2 GAD trial, we believe there is a strong clinical and translational rationale to advance BNC210 for the acute treatment of patients with SAD, which we believe now has a defined clinical and regulatory pathway based on the positive outcome of the End-of-Phase 2 meeting with the FDA in September 2023 that enables advancement of BNC210 into Phase 3 studies in SAD.
Based on the favorable rapid absorption profile of our novel tablet formulation and evidence of anti-anxiety effect from our prior Phase 1b panic attack trial and our Phase 2 GAD trial, we believe there is a strong clinical and translational rationale to advance BNC210 for the acute treatment of patients with SAD, which we believe now has a defined clinical and regulatory pathway based on the positive outcome of the End-of-Phase 2 meeting with the FDA in September 2023 that enabled advancement of BNC210 into Phase 3 in SAD.
We also have two patent families with claims directed to the composition of matter and their uses for the treatment of cognitive deficits and negative symptoms in schizophrenia and for the treatment of autism spectrum disorders, and are currently pending in the U.S., Europe, Australia, Japan, Canada, and New Zealand.
We also have two patent families with claims directed to the composition of matter and their uses for the treatment of cognitive deficits and negative symptoms in schizophrenia and for the treatment of autism spectrum disorders, and are currently granted in US, Europe and Australia; and are pending in the Japan, Canada, and New Zealand.
As such, we are dependent on MSD to provide us with any updates related to clinical trial results, serious adverse events and ongoing communications with FDA related to these programs, which MSD may provide or withhold in its sole discretion, and as a result we may not be able to provide material updates on a timely basis or at all with respect to these programs.
As such, we are dependent on Merck to provide us with any updates related to clinical trial results, serious adverse events and ongoing communications with FDA or other regulatory agencies related to these programs, which Merck may provide or withhold in its sole discretion, and as a result we may not be able to provide material updates on a timely basis or at all with respect to these programs.
Our first legacy oncology program is BNC101, a novel humanized monoclonal antibody that targets LGR5, a cancer stem cell receptor highly overexpressed in most solid tumors. In November 2020, we exclusively licensed BNC101 to Carina Biotech for the development of chimeric receptor antigen T-cell (“CAR-T”) therapeutics in return for milestones and royalties.
Our first legacy oncology program is BNC101, a novel humanized monoclonal antibody that targets LGR5, a cancer stem cell receptor highly overexpressed in most solid tumors. In November 2020, we exclusively licensed BNC101 to Carina for the development of chimeric receptor antigen T-cell (“CAR-T”) therapeutics.
Additionally, we are aware of several product candidates in clinical development that are being developed for the acute treatment of SAD, by VistaGen Therapeutics and Vanda Pharmaceuticals, among others.
Additionally, we are aware of several product candidates in clinical development that are being developed for the acute treatment of SAD, by VistaGen Therapeutics, among others.
We have administered BNC210 in approximately 600 subjects across 14 completed clinical trials, including healthy volunteers, elderly patients with agitation and patients with Generalized Anxiety Disorder (“GAD”), SAD and PTSD. We have observed BNC210 to be generally well tolerated in the trials to date following both acute and chronic dosing.
We have administered BNC210 to approximately 790 subjects across 15 clinical trials, including healthy volunteers, elderly patients with agitation and patients with Generalized Anxiety Disorder (“GAD”), SAD and PTSD. We have observed BNC210 to be generally well tolerated in the trials to date following both acute and chronic dosing.
The meeting, held on June 26, 2024, was centered around the design of the Phase 3 trial that if successful may enable review of the NDA submission.
The meeting, held on June 26, 2024, was centered around the design of this trial that if successful may enable review of the NDA submission.
The BNC210 tablet formulation had a rapid absorption profile reaching maximal concentrations in the blood between 45 to 105 minutes, potentially making it a well-suited formulation for treatment of acute anxiety in SAD patients in the ongoing Phase 2 PREVAIL trial. BNC210 was observed in this study to be well tolerated at all dose levels tested.
The BNC210 tablet formulation had a rapid absorption profile reaching maximal concentrations in the blood between 45 to 105 minutes, making it a well-suited formulation for treatment of acute anxiety in SAD patients. BNC210 was observed in this study to be well tolerated at all dose levels tested.
Further, we are subject to limited information rights under the 2014 MSD License Agreement.
Further, we are subject to limited information rights under the 2014 Merck License Agreement.
Further, in our clinical trials in GAD patients and in panic-induced healthy subjects, we have observed three key results: ● statistically significant reductions in hyperactivity in the amygdala, the region of the brain responsible for emotional control, when exposed to fear-inducing triggers; ● in a head-to-head study, showed a statistically significant reduction in the intensity of defensive behavior, while lorazepam, a widely prescribed benzodiazepine did not; and ● a statistically significant reduction in the intensity and total number of panic symptoms as well as more rapid recovery from the panic state relative to placebo.
Further, in our clinical trials in GAD patients and in panic-induced healthy subjects, we have observed three key results: • statistically significant reductions in hyperactivity in the amygdala, the region of the brain responsible for emotional control, when exposed to fear-inducing triggers; • in a head-to-head study, showed a statistically significant reduction in the intensity of defensive behavior, while lorazepam, a widely prescribed benzodiazepine did not; and • a statistically significant reduction in the intensity and total number of panic symptoms.
Intellectual Property Central Nervous System As of June 30, 2024, we owned over 15 issued U.S. patents, four pending U.S. patent applications, two pending Patent Cooperation Treaty (“PCT”) applications, over 30 granted foreign patents, and over 15 pending foreign patent applications in our central nervous system intellectual property portfolio.
Intellectual Property Central Nervous System As of June 30, 2025, we owned over 15 issued U.S. patents, one pending U.S. patent applications, two pending Patent Cooperation Treaty (“PCT”) applications, over 30 granted foreign patents, and over 10 pending foreign patent applications in our central nervous system intellectual property portfolio.
When BNC210 binds to the α7 receptor in the presence of ACh, it normalizes the effect of enhanced ACh signaling, thereby decreasing the flow of Ca2+ through the channel and the subsequent downstream neurotransmitter modulation, as seen in Figure 3.
When BNC210 binds to the α7 receptor in the presence of ACh, it normalizes the effect of enhanced ACh signaling, thereby decreasing the flow of Ca 2+ through the channel and the subsequent downstream neurotransmitter modulation, as seen in Figure 4.
On 24 January 2023, Carina announced that it had received an FDA “Safe to Proceed” Letter for a Phase 1/2a clinical trial of BNC101 CAR-T therapy for the treatment of advanced colorectal cancer and plans to commence patient enrollment during the first half of 2023. In December 2023, Carina announced that patient dosing for their Phase 1/2a study had commenced.
On 24 January 2023, Carina announced that it had received an FDA “Safe to Proceed” Letter for a Phase 1/2a clinical trial of BNC101 CAR-T therapy for the treatment of advanced colorectal cancer. In December 2023, Carina announced that patient dosing for their Phase 1/2a study had commenced.
As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our product candidates to each payor separately, with no assurance that coverage and adequate reimbursement will be obtained.
Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our product candidates to each payor separately, with no assurance that coverage and adequate reimbursement will be obtained.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.
In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.
Among the provisions of the ACA, those of greatest importance to the biotechnology and pharmaceutical industries are the following: ● an annual, non-deductible fee payable by any entity that manufactures or imports certain branded prescription drugs and biologic agents (other than those designated as orphan drugs), which is apportioned among these entities according to their market share in certain government healthcare programs; ● a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (increased to 70% pursuant to the Bipartisan Budget Act of 2018, effective as of January 1, 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; ● an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded and generic drugs, respectively; ● a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected; ● extension of a manufacturer’s Medicaid rebate obligation to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations; ● expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability; ● a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and ● establishment of the Center for Medicare and Medicaid Innovation at the Centers for Medicare & Medicaid Services (“CMS”) to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.
Among the provisions of the ACA, those of greatest importance to the biotechnology and pharmaceutical industries are the following: • an annual, non-deductible fee payable by any entity that manufactures or imports certain branded prescription drugs and biologic agents (other than those designated as orphan drugs), which is apportioned among these entities according to their market share in certain government healthcare programs; • a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (increased to 70% pursuant to the Bipartisan Budget Act of 2018, effective as of January 1, 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; • an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded and generic drugs, respectively; • a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected; • extension of a manufacturer’s Medicaid rebate obligation to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations; • expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability; 71 • a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and • establishment of the Center for Medicare and Medicaid Innovation at the Centers for Medicare & Medicaid Services (“CMS”) to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.
In addition, if our current or future product candidates receive marketing approval and we or others identify undesirable side effects caused by such current or future product candidates after such approval, a number of potentially significant negative consequences could result, including: ● regulatory authorities may suspend, withdraw or limit approvals of such current or future product candidates, or seek an injunction against their manufacture or distribution; ● regulatory authorities may require the addition of labeling statements or warnings, such as a “boxed” warning or a contraindication, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; ● we may be required to create a medication guide outlining the risks of such side effects for distribution to patients; ● we may be required to change the way such current or future product candidates are distributed or administered, conduct additional clinical trials or change the labeling of the current or future product candidates; ● we may be required to conduct post-marketing studies or change the way the product is administered; ● regulatory authorities may require a Risk Evaluation and Mitigation Strategy (“REMS”) plan to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools; ● we may be subject to regulatory investigations and government enforcement actions; ● we may decide to remove such current or future product candidates from the market; 55 ● we could be sued and held liable for injury caused to individuals exposed to or taking our current or future product candidates; ● we may be subject to fines, injunctions or imposition of criminal penalties; and ● our reputation may suffer.
In addition, if our current or future product candidates receive marketing approval and we or others identify undesirable side effects caused by such current or future product candidates after such approval, a number of potentially significant negative consequences could result, including: • regulatory authorities may suspend, withdraw or limit approvals of such current or future product candidates, or seek an injunction against their manufacture or distribution; • regulatory authorities may require the addition of labeling statements or warnings, such as a “boxed” warning or a contraindication, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; • we may be required to create a medication guide outlining the risks of such side effects for distribution to patients; • we may be required to change the way such current or future product candidates are distributed or administered, conduct additional clinical trials or change the labeling of the current or future product candidates; • we may be required to conduct post-marketing studies or change the way the product is administered; • regulatory authorities may require a Risk Evaluation and Mitigation Strategy (“REMS”) plan to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools; • we may be subject to regulatory investigations and government enforcement actions; • we may decide to remove such current or future product candidates from the market; • we could be sued and held liable for injury caused to individuals exposed to or taking our current or future product candidates; • we may be subject to fines, injunctions or imposition of criminal penalties; and • our reputation may suffer.
Later discovery of previously unknown problems with a drug, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: ● restrictions on the marketing or manufacturing of our product candidates, withdrawal of the product from the market, or voluntary or mandatory product recalls; ● manufacturing delays and supply disruptions where regulatory inspections identify observations of noncompliance during remediation; ● revisions to the labeling, including limitation on approved uses or the addition of warnings, contraindications, or other safety information, including boxed warnings; ● imposition of a REMS, which may include distribution or use restrictions; ● requirements to conduct additional post-market clinical trials to assess the safety of the product; ● fines, warning or untitled letters or holds on clinical trials; ● refusal by the FDA to approve pending applications or supplements to approved applications filed by us, or suspension or withdrawal of approvals; ● product seizure or detention, or refusal to permit the import or export of drugs; and ● injunctions or the imposition of civil or criminal penalties.
Later discovery of previously unknown problems with a drug, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: • restrictions on the marketing or manufacturing of our product candidates, withdrawal of the product from the market, or voluntary or mandatory product recalls; • manufacturing delays and supply disruptions where regulatory inspections identify observations of noncompliance during remediation; • revisions to the labeling, including limitation on approved uses or the addition of warnings, contraindications, or other safety information, including boxed warnings; • imposition of a REMS, which may include distribution or use restrictions; • requirements to conduct additional post-market clinical trials to assess the safety of the product; • fines, warning or untitled letters or holds on clinical trials; • refusal by the FDA to approve pending applications or supplements to approved applications filed by us, or suspension or withdrawal of approvals; 51 • product seizure or detention, or refusal to permit the import or export of drugs; and • injunctions or the imposition of civil or criminal penalties.
Applications for our product candidates could fail to receive regulatory approval for many reasons, including but not limited to the following: ● the FDA, EMA or other comparable regulatory authorities may disagree with the design or implementation of our, or our collaboration partners’, clinical trials; ● the population studied in the clinical program may not be sufficiently broad or representative to assure safety in the full population for which approval is sought; ● the FDA, EMA or comparable regulatory authorities may disagree with the interpretation of data from preclinical studies or clinical trials; 77 ● the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an NDA, a BLA, marketing authorization application, or other submission or to obtain regulatory approval in the United States, the EEA, Australia or elsewhere; ● we, or our collaboration partners, may be unable to demonstrate to the FDA, EMA or comparable regulatory authorities that a product candidate’s risk-benefit ratio for its proposed indication is acceptable; ● the FDA, EMA or comparable regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications, or facilities of third-party manufacturers responsible for clinical and commercial supplies; and ● the approval policies or regulations of the FDA, EMA or comparable regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Applications for our product candidates could fail to receive regulatory approval for many reasons, including but not limited to the following: • the FDA, EMA or other comparable regulatory authorities may disagree with the design or implementation of our, or our collaboration partners’, clinical trials; • the population studied in the clinical program may not be sufficiently broad or representative to assure safety in the full population for which approval is sought; • the FDA, EMA or comparable regulatory authorities may disagree with the interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an NDA, a BLA, marketing authorization application, or other submission or to obtain regulatory approval in the United States, the EEA, Australia or elsewhere; • we, or our collaboration partners, may be unable to demonstrate to the FDA, EMA or comparable regulatory authorities that a product candidate’s risk-benefit ratio for its proposed indication is acceptable; • the FDA, EMA or comparable regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications, or facilities of third-party manufacturers responsible for clinical and commercial supplies; and • the approval policies or regulations of the FDA, EMA or comparable regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
In addition to the risks inherent in the development of a product candidate, factors that may affect the success of our collaborations include the following: ● our collaboration partners have the unilateral ability to choose not to develop a collaboration drug for one or more indications for which such drug has been or is currently being evaluated, and our collaboration partners may choose to pursue an indication that is not in our strategic best interest or to forego an indication that they believe does not provide significant market potential even if clinical data are supportive of further development for such indication; ● our collaboration partners may choose not to develop and commercialize our collaboration product candidates in certain relevant markets; 63 ● our collaboration partners may take considerably more time advancing our product candidates through the clinical and regulatory process than we currently anticipate, which could materially delay the achievement of milestones and, consequently the receipt of milestone payments from our collaboration partners; ● our collaboration partners may not inform us regarding the progress of compounds, including but not limited to whether a decision is made to advance certain compounds; ● our collaboration partners have substantial discretion under their respective agreements regarding how they structure their efforts and allocate resources to fulfil their obligations to diligently develop, manufacture, obtain regulatory approval for and commercialize our collaboration drugs; ● our collaboration partners control all aspects of commercialization efforts under their respective collaboration and license agreements and may change the focus of their development and commercialization efforts or pursue higher-priority programs and, accordingly, reduce the efforts and resources allocated to their collaborations with us; ● our collaboration partners may not pursue all indications eligible for milestones; ● our collaboration partners are solely responsible for obtaining and maintaining all regulatory approvals and may fail to develop a commercially viable formulation or manufacturing process for our product candidates, and may fail to manufacture or supply sufficient drug product for commercial use, if approved, which could result in lost revenue; ● our collaboration partners may not comply with all applicable regulatory requirements or may fail to report safety data in accordance with all applicable regulatory requirements; ● if any of our agreements with our collaboration partners terminate, we will no longer have any rights to receive potential revenue under such agreement, in which case we would need to identify alternative means to continue the development, manufacture and commercialization of the affected product candidates, alone or with others; ● our collaboration may have to license other patents to enable marketing of compound, and our royalties may be reduced; ● our collaboration partners have the discretion to sublicense their rights with respect to our collaboration technology in connection with collaboration product candidates to one or more third parties without our consent; ● our collaboration partners may be pursuing alternative technologies or developing alternative drugs, either on their own or in collaboration with others, that may be competitive with drugs on which they are collaborating with us or which could affect our collaboration partners’ commitment to the collaboration; and ● if our collaboration partners receive approval for any of the collaboration product candidates, reductions in marketing or sales efforts or a discontinuation of marketing or sales of our product candidates by our collaboration partners would reduce any milestones and royalties we could be entitled to receive.
In addition to the risks inherent in the development of a product candidate, factors that may affect the success of our collaborations include the following: • our collaboration partners have the unilateral ability to choose not to develop a collaboration drug for one or more indications for which such drug has been or is currently being evaluated, and our collaboration partners may choose to pursue an indication that is not in our strategic best interest or to forego an indication that they believe does not provide significant market potential even if clinical data are supportive of further development for such indication; • our collaboration partners may choose not to develop and commercialize our collaboration product candidates in certain relevant markets; • our collaboration partners may take considerably more time advancing our product candidates through the clinical and regulatory process than we currently anticipate, which could materially delay the achievement of milestones and, consequently the receipt of milestone payments from our collaboration partners; • our collaboration partners may not inform us regarding the progress of compounds, including but not limited to whether a decision is made to advance certain compounds; • our collaboration partners have substantial discretion under their respective agreements regarding how they structure their efforts and allocate resources to fulfil their obligations to diligently develop, manufacture, obtain regulatory approval for and commercialize our collaboration drugs; • our collaboration partners control all aspects of commercialization efforts under their respective collaboration and license agreements and may change the focus of their development and commercialization efforts or pursue higher-priority programs and, accordingly, reduce the efforts and resources allocated to their collaborations with us; • our collaboration partners may not pursue all indications eligible for milestones; • our collaboration partners are solely responsible for obtaining and maintaining all regulatory approvals and may fail to develop a commercially viable formulation or manufacturing process for our product candidates, and may fail to manufacture or supply sufficient drug product for commercial use, if approved, which could result in lost revenue; 57 • our collaboration partners may not comply with all applicable regulatory requirements or may fail to report safety data in accordance with all applicable regulatory requirements; • if any of our agreements with our collaboration partners terminate, we will no longer have any rights to receive potential revenue under such agreement, in which case we would need to identify alternative means to continue the development, manufacture and commercialization of the affected product candidates, alone or with others; • our collaboration may have to license other patents to enable marketing of compound, and our royalties may be reduced; • our collaboration partners have the discretion to sublicense their rights with respect to our collaboration technology in connection with collaboration product candidates to one or more third parties without our consent; • our collaboration partners may be pursuing alternative technologies or developing alternative drugs, either on their own or in collaboration with others, that may be competitive with drugs on which they are collaborating with us or which could affect our collaboration partners’ commitment to the collaboration; and • if our collaboration partners receive approval for any of the collaboration product candidates, reductions in marketing or sales efforts or a discontinuation of marketing or sales of our product candidates by our collaboration partners would reduce any milestones and royalties we could be entitled to receive.
Any potential intellectual property litigation also could force us to do one or more of the following: ● stop making, selling or using products or technologies that allegedly infringe the asserted intellectual property; ● lose the opportunity to license our technology to others or to collect royalty payments based upon successful protection and assertion of our intellectual property rights against others; 91 ● incur significant legal expenses; ● pay substantial damages or royalties to the party whose intellectual property rights we may be found to be infringing; ● pay the attorney’s fees and costs of litigation to the party whose intellectual property rights we may be found to be infringing; ● redesign those products that contain the allegedly infringing intellectual property, which could be costly, disruptive and infeasible; and ● attempt to obtain a license to the relevant intellectual property from third parties, which may not be available on reasonable terms or at all, or from third parties who may attempt to license rights that they do not have.
Any potential intellectual property litigation also could force us to do one or more of the following: • stop making, selling or using products or technologies that allegedly infringe the asserted intellectual property; • lose the opportunity to license our technology to others or to collect royalty payments based upon successful protection and assertion of our intellectual property rights against others; • incur significant legal expenses; • pay substantial damages or royalties to the party whose intellectual property rights we may be found to be infringing; • pay the attorney’s fees and costs of litigation to the party whose intellectual property rights we may be found to be infringing; • redesign those products that contain the allegedly infringing intellectual property, which could be costly, disruptive and infeasible; and • attempt to obtain a license to the relevant intellectual property from third parties, which may not be available on reasonable terms or at all, or from third parties who may attempt to license rights that they do not have.
Disputes may arise between us and our licensors regarding intellectual property subject to a license agreement, including: ● the scope of rights granted under the license agreement and other interpretation-related issues; ● whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; ● our right to sublicense patents and other rights to third parties; ● our diligence obligations with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates, and what activities satisfy those diligence obligations; ● our right to transfer or assign the license; and ● the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners.
Disputes may arise between us and our licensors regarding intellectual property subject to a license agreement, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; 77 • our right to sublicense patents and other rights to third parties; • our diligence obligations with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates, and what activities satisfy those diligence obligations; • our right to transfer or assign the license; and • the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners.
Department of Health and Human Services (“HHS”), Office of Inspector General (“OIG”), heavily scrutinizes relationships between pharmaceutical companies and persons in a position to generate referrals for or the purchase of their products, such as physicians, other healthcare providers, and pharmacy benefit managers, among others; ● the federal civil monetary penalty laws and civil and criminal false claims laws and, such as the federal False Claims Act, which imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the U.S.
Department of Health and Human Services (“HHS”), Office of Inspector General (“OIG”), heavily scrutinizes relationships 69 between pharmaceutical companies and persons in a position to generate referrals for or the purchase of their products, such as physicians, other healthcare providers, and pharmacy benefit managers, among others; • the federal civil monetary penalty laws and civil and criminal false claims laws and, such as the federal False Claims Act, which imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the U.S.
American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers. ● On April 13, 2017, CMS published a final rule that gives states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces. 82 ● On May 30, 2018, the Right to Try Act, was signed into law.
American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers. • On April 13, 2017, CMS published a final rule that gives states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces. • On May 30, 2018, the Right to Try Act, was signed into law.
We expect that we are or will be subject to additional risks related to entering into these international business markets and relationships, including: ● different regulatory requirements for product and biologics approvals in foreign countries; ● differing U.S. and non-U.S. drug import and export rules; ● reduced protection for intellectual property rights in foreign countries; ● unexpected changes in tariffs, trade barriers and regulatory requirements; ● different reimbursement systems, and different competitive drugs and biologics; 60 ● economic weakness, including inflation, or political instability in particular foreign economies and markets; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign taxes, including withholding of payroll taxes; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; ● workforce uncertainty in countries where labor unrest is more common than in the United States; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; ● potential liability resulting from development work conducted by distributors; and ● business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters.
We expect that we are or will be subject to additional risks related to entering into these international business markets and relationships, including: • different regulatory requirements for product and biologics approvals in foreign countries; • differing U.S. and non-U.S. drug import and export rules; • reduced protection for intellectual property rights in foreign countries; • unexpected changes in tariffs, trade barriers and regulatory requirements; • different reimbursement systems, and different competitive drugs and biologics; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign taxes, including withholding of payroll taxes; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; • workforce uncertainty in countries where labor unrest is more common than in the United States; 54 • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; • potential liability resulting from development work conducted by distributors; and • business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters.
Market acceptance of our current or future product candidates, if approved, will depend on a number of factors, including, among others: ● the efficacy of our current or future product candidates as demonstrated in clinical trials, and, if required by any applicable regulatory authority in connection with the approval for the applicable indications, to provide patients with incremental health benefits, as compared with other available medicines; 72 ● the timing of market introduction of the product candidates and potential advantages to alternative treatments; ● limitations or warnings contained in the labeling approved for our current or future product candidates by the FDA or other applicable regulatory authorities; ● the clinical indications for which our current or future product candidates are approved; ● availability of alternative treatments already approved or expected to be commercially launched in the near future; ● the potential and perceived advantages of our current or future product candidates over current treatment options or alternative treatments, including future alternative treatments; ● the willingness of the target patient population to try new therapies or treatment methods and of physicians to prescribe these therapies or methods; ● the need to dose such product candidates in combination with other therapeutic agents, and related costs; ● the strength of marketing and distribution support and timing of market introduction of competitive products; ● publicity concerning our products or competing products and treatments; ● our ability to obtain and maintain intellectual property protection; ● pricing and cost effectiveness; ● the effectiveness of our sales and marketing strategies; ● our ability to increase awareness of our current or future product candidates; ● our ability to obtain sufficient third-party coverage or reimbursement; or ● the willingness of patients to pay out-of-pocket in the absence of third-party coverage.
Market acceptance of our current or future product candidates, if approved, will depend on a number of factors, including, among others: • the efficacy of our current or future product candidates as demonstrated in clinical trials, and, if required by any applicable regulatory authority in connection with the approval for the applicable indications, to provide patients with incremental health benefits, as compared with other available medicines; • the timing of market introduction of the product candidates and potential advantages to alternative treatments; • limitations or warnings contained in the labeling approved for our current or future product candidates by the FDA or other applicable regulatory authorities; • the clinical indications for which our current or future product candidates are approved; • availability of alternative treatments already approved or expected to be commercially launched in the near future; • the potential and perceived advantages of our current or future product candidates over current treatment options or alternative treatments, including future alternative treatments; • the willingness of the target patient population to try new therapies or treatment methods and of physicians to prescribe these therapies or methods; • the need to dose such product candidates in combination with other therapeutic agents, and related costs; • the strength of marketing and distribution support and timing of market introduction of competitive products; • publicity concerning our products or competing products and treatments; • our ability to obtain and maintain intellectual property protection; 63 • pricing and cost effectiveness; • the effectiveness of our sales and marketing strategies; • our ability to increase awareness of our current or future product candidates; • our ability to obtain sufficient third-party coverage or reimbursement; or • the willingness of patients to pay out-of-pocket in the absence of third-party coverage.
Factors that may inhibit our efforts to market our products on our own include: ● our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel; ● the inability of sales personnel to obtain access to physicians in order to educate physicians about our product candidates, once approved; 73 ● the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and ● unforeseen costs and expenses associated with creating an independent sales and marketing organization.
Factors that may inhibit our efforts to market our products on our own include: • our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to physicians in order to educate physicians about our product candidates, once approved; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and • unforeseen costs and expenses associated with creating an independent sales and marketing organization.
In addition, failure to comply with FDA and other applicable U.S., EEA and other comparable regulatory requirements may subject us to administrative or judicially imposed sanctions or other actions, including: ● untitled or warning letters; ● civil and criminal penalties; 76 ● injunctions; ● withdrawal of regulatory approval of drugs; ● drug seizure or detention; ● drug recalls; ● total or partial suspension of production; and ● refusal to approve pending NDAs, BLAs, marketing authorization applications, or supplements to approved NDAs, BLAs or extensions or variations to marketing authorizations.
In addition, failure to comply with FDA and other applicable U.S., EEA and other comparable regulatory requirements may subject us to administrative or judicially imposed sanctions or other actions, including: • untitled or warning letters; • civil and criminal penalties; • injunctions; • withdrawal of regulatory approval of drugs; • drug seizure or detention; • drug recalls; • total or partial suspension of production; and • refusal to approve pending NDAs, BLAs, marketing authorization applications, or supplements to approved NDAs, BLAs or extensions or variations to marketing authorizations.
Patient enrollment for any of our future clinical trials may be affected by other factors including: ● the size and nature of the patient population; ● competition with other companies for clinical sites or patients; ● the willingness of participants to enroll in our clinical trials in our countries of interest; ● the severity of the disease under investigation; ● availability and efficacy of approved drugs for the disease under investigation; ● the eligibility criteria for the clinical trial in question as defined in the protocol; ● the availability of an appropriate screening test(s) for the indications we are pursuing; ● the perceived risks and benefits of the product candidate under study in relation to other available therapies, including any new products that may be approved for the indications we are investigating; 52 ● the efforts to facilitate timely enrollment in and completion of clinical trials; ● delays in or temporary suspension of the enrollment of patients in our then ongoing or future clinical trials in the event of a future pandemic; ● ability to obtain and maintain patient consents; ● the patient referral practices of physicians; ● the ability to monitor patients adequately during and after treatment; ● the proximity and availability of clinical trial sites for prospective patients; and ● the risk that patients enrolled in clinical trials will drop out of the trials before completion.
Patient enrollment for any of our future clinical trials may be affected by other factors including: • the size and nature of the patient population; • competition with other companies for clinical sites or patients; • the willingness of participants to enroll in our clinical trials in our countries of interest; • the severity of the disease under investigation; • availability and efficacy of approved drugs for the disease under investigation; • the eligibility criteria for the clinical trial in question as defined in the protocol; • the availability of an appropriate screening test(s) for the indications we are pursuing; • the perceived risks and benefits of the product candidate under study in relation to other available therapies, including any new products that may be approved for the indications we are investigating; • the efforts to facilitate timely enrollment in and completion of clinical trials; 47 • delays in or temporary suspension of the enrollment of patients in our then ongoing or future clinical trials in the event of a future pandemic; • ability to obtain and maintain patient consents; • the patient referral practices of physicians; • the ability to monitor patients adequately during and after treatment; • the proximity and availability of clinical trial sites for prospective patients; and • the risk that patients enrolled in clinical trials will drop out of the trials before completion.
While we seek to maintain adequate inventory of the drug product and drug substance used in our current or future product candidates, any interruption or delay in the supply of components or materials, or our inability to obtain drug product and drug substance from alternate sources at acceptable prices in a timely manner, could impede, delay, limit or prevent our development efforts, which could harm our business, results of operations, financial condition and prospects.
While we seek to maintain adequate inventory of the drug product and drug substance used in our current or future product candidates, any interruption or delay in the supply of components or materials, or our inability to obtain drug product and drug substance from 60 alternate sources at acceptable prices in a timely manner, could impede, delay, limit or prevent our development efforts, which could harm our business, results of operations, financial condition and prospects.
Since patent applications in the United States and most other countries are confidential for a period of time after filing or until issuance, we cannot be certain that we or our licensors were the first to either (i) file any patent application related to our product candidates and other proprietary technologies we may develop or (ii) invent any of the inventions claimed in our or our licensor’s patents or patent applications.
Since patent applications in the United States and most other countries are confidential for a period of time after filing or until issuance, we cannot be certain that we or our licensors were the first to either (i) file any patent application related to our product candidates and other proprietary technologies we may develop or (ii) 76 invent any of the inventions claimed in our or our licensor’s patents or patent applications.
A Breakthrough Therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
A Breakthrough Therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary 50 clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
Additionally, on April 15, 2021, the FDA began conducting voluntary remote interactive evaluations of certain drug manufacturing facilities and clinical research sites, among other facilities in circumstances where the FDA determines that such remote evaluation would be appropriate based on mission needs and travel limitations. In July 2021, the FDA resumed standard inspectional operations of domestic facilities.
Additionally, on 52 April 15, 2021, the FDA began conducting voluntary remote interactive evaluations of certain drug manufacturing facilities and clinical research sites, among other facilities in circumstances where the FDA determines that such remote evaluation would be appropriate based on mission needs and travel limitations. In July 2021, the FDA resumed standard inspectional operations of domestic facilities.
With respect to our current product candidates, if our current or future nonclinical or clinical studies fail to produce positive results, the development timeline and regulatory approval and commercialization prospects for these candidates and, correspondingly, our business and financial prospects, as well as the value of our securities, including our Ordinary Shares and ADSs, could be materially adversely affected.
With respect to our current product candidates, if our 48 current or future nonclinical or clinical studies fail to produce positive results, the development timeline and regulatory approval and commercialization prospects for these candidates and, correspondingly, our business and financial prospects, as well as the value of our securities, including our Ordinary Shares and ADSs, could be materially adversely affected.
The key competitive factors affecting the success of all of our current or future product candidates, if approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors. 74 Third-party payor coverage and reimbursement status of newly-approved drugs is uncertain.
The key competitive factors affecting the success of all of our current or future product candidates, if approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors. Third-party payor coverage and reimbursement status of newly-approved drugs is uncertain.
Risks Related to Our Reliance on Third Parties If our collaboration partners fail to perform as expected, fail to advance our collaboration product candidates, are unable to obtain the required regulatory approvals for our collaboration product candidates, or if the arrangements are terminated, the potential for us to generate future revenue from such product candidates would be significantly reduced and our business would be significantly harmed.
Risks Related to Our Reliance on Third Parties If our collaboration partners fail to perform as expected, fail to advance our collaboration product candidates, are unable to obtain the required regulatory approvals for our collaboration product candidates, or if the arrangements are 56 terminated, the potential for us to generate future revenue from such product candidates would be significantly reduced and our business would be significantly harmed.
If any of the physicians or other providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to similar criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs and imprisonment.
If any of the physicians or other providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to similar criminal, civil or 70 administrative sanctions, including exclusions from government funded healthcare programs and imprisonment.
Our competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner. 85 The issuance of a patent is not conclusive as to its scope, validity or enforceability, and our owned and in-licensed patents may be challenged in the courts or patent offices in the United States and abroad.
Our competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner. The issuance of a patent is not conclusive as to its scope, validity or enforceability, and our owned and in-licensed patents may be challenged in the courts or patent offices in the United States and abroad.
However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business, financial condition, results of operations and prospects. 87 In addition, the U.S.
However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business, financial condition, results of operations and prospects. In addition, the U.S.
Any efforts to enforce our intellectual property rights are also likely to be costly and may divert the efforts of our scientific and management personnel. 90 Litigation or other proceedings or third-party claims of intellectual property infringement could require us to spend significant time and money and could prevent us from developing or selling our products.
Any efforts to enforce our intellectual property rights are also likely to be costly and may divert the efforts of our scientific and management personnel. Litigation or other proceedings or third-party claims of intellectual property infringement could require us to spend significant time and money and could prevent us from developing or selling our products.
Regardless of their merit or eventual outcome, product liability claims may result in: ● decreased demand for any of our future drugs; ● injury to our reputation and significant negative media attention; ● withdrawal of clinical trial participants; ● costs of litigation; ● distraction of management; and ● substantial monetary awards to plaintiffs.
Regardless of their merit or eventual outcome, product liability claims may result in: • decreased demand for any of our future drugs; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants; 66 • costs of litigation; • distraction of management; and • substantial monetary awards to plaintiffs.
While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction.
While an inadvertent lapse can in many cases be cured 75 by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction.
Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization of new drugs. There are currently no FDA-approved drugs for the acute treatment of SAD.
Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct 64 research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization of new drugs. There are currently no FDA-approved drugs for the acute treatment of SAD.
In addition, approval policies, regulations or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, which may cause delays in the approval or result in a decision not to approve an application for regulatory approval.
In addition, approval policies, regulations or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical 67 development and may vary among jurisdictions, which may cause delays in the approval or result in a decision not to approve an application for regulatory approval.
Many compounds that initially showed promise in early-stage testing have later been found to cause side effects that prevented further development of the compound. In addition, clinical trials by their nature utilize a sample of the potential patient population.
Many compounds that initially showed promise in early-stage testing have later been found to cause side effects that prevented further development of the compound. 49 In addition, clinical trials by their nature utilize a sample of the potential patient population.
Fluctuations in our operating results may occur due to a variety of factors, many of which are out of our control and may be difficult to predict, including: ● the timing and cost of, and level of investment in, research, development, regulatory approval and commercialization activities relating to our product candidates, which may change from time to time; ● the timing of milestone payments, if any, under our license and collaboration agreements; ● the timing and amount of royalty or other payments, if any, under our license and collaboration agreements; ● expenditures that we may incur to acquire, develop, or commercialize additional product candidates and technologies; ● the level of demand for our current or future product candidates, if approved, which may vary significantly; ● coverage and reimbursement policies with respect to our product candidates, if approved, and existing and potential future drugs that compete with our product candidates; ● the cost of manufacturing our product candidates, which may vary depending on the quantity of production and the terms of our agreements with third-party manufacturers; ● the timing and success or failure of clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, including consolidation of our competitors or partners; ● the timing and exercise, if any, of outstanding warrants and options; ● foreign currency fluctuations; and ● future accounting pronouncements or changes in our accounting policies.
Fluctuations in our operating results may occur due to a variety of factors, many of which are out of our control and may be difficult to predict, including: • the timing and cost of, and level of investment in, research, development, regulatory approval and commercialization activities relating to our product candidates, which may change from time to time; • the timing of milestone payments, if any, under our license and collaboration agreements; • the timing and amount of royalty or other payments, if any, under our license and collaboration agreements; • expenditures that we may incur to acquire, develop, or commercialize additional product candidates and technologies; 43 • the level of demand for our current or future product candidates, if approved, which may vary significantly; • coverage and reimbursement policies with respect to our product candidates, if approved, and existing and potential future drugs that compete with our product candidates; • the cost of manufacturing our product candidates, which may vary depending on the quantity of production and the terms of our agreements with third-party manufacturers; • the timing and success or failure of clinical trials for our product candidates or competing product candidates, or any other change in the competitive landscape of our industry, including consolidation of our competitors or partners; • the timing and exercise, if any, of outstanding warrant and options; • foreign currency fluctuations; and • future accounting pronouncements or changes in our accounting policies.
If we are unable to rely on clinical data collected by our CROs, we could be required to repeat, extend the duration of, or increase the size of any clinical trials we conduct and this could significantly delay commercialization and require significantly greater expenditures.
If we are unable to rely on clinical data collected by our CROs, we could be required to repeat, extend the duration of, or increase the 59 size of any clinical trials we conduct and this could significantly delay commercialization and require significantly greater expenditures.
The patenting process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, we may not pursue or obtain patent protection in all relevant markets.
The 74 patenting process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. In addition, we may not pursue or obtain patent protection in all relevant markets.
If we fail to maintain the patents and patent applications covering our product candidates, our competitive position would be adversely affected. 86 Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time. Patents have a limited lifespan.
If we fail to maintain the patents and patent applications covering our product candidates, our competitive position would be adversely affected. Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time. Patents have a limited lifespan.
Factors payors consider in determining reimbursement are based on whether the product is: ● a covered benefit under its health plan; ● safe, effective and medically necessary; ● appropriate for the specific patient; ● cost-effective; and ● neither experimental nor investigational.
Factors payors consider in determining reimbursement are based on whether the product is: • a covered benefit under its health plan; 65 • safe, effective and medically necessary; • appropriate for the specific patient; • cost-effective; and • neither experimental nor investigational.
We are also unable to predict when, if ever, we will be able to generate revenue from such product candidates due to the numerous risks and uncertainties associated with drug development, including the uncertainty of: ● our ability to timely and successfully complete preclinical studies and clinical trials for BNC210 and other current or future product candidates; ● the ability of our existing or future licensees and collaborators to successfully develop and commercialize product candidates pursuant to collaboration agreements, including MSD with respect to its two product candidates and Carina Biotech with respect to BNC101; ● our successful initiation, enrollment in and completion of clinical trials for BNC210 and other current or future product candidates, including our ability to generate positive data from any such clinical trials; ● our ability to demonstrate to the satisfaction of the FDA and comparable regulatory authorities the safety, efficacy, consistent manufacturing quality and acceptable risk-benefit profile of our product candidates for their intended uses; ● our plans to submit NDAs to the FDA for BNC210 and future product candidates; ● our ability to obtain in a timely manner necessary approvals or authorizations from applicable regulatory authorities; ● the costs associated with the development of any additional development programs we identify in-house or acquire through collaborations or other arrangements; ● our ability to establish manufacturing capabilities or make arrangements with third-party manufacturers for clinical supply and commercial manufacturing; ● our ability to advance our early-stage CNS assets into IND-enabling studies either on our own or through collaborations; 51 ● obtaining and maintaining patent and trade secret protection or regulatory exclusivity for our current and future product candidates; ● launching commercial sales of our product candidates, if and when approved, whether alone or in collaboration with others; ● obtaining and maintaining acceptance of our product candidates, if and when approved, by patients, the medical community and third-party payors; ● effectively competing with other therapies; ● obtaining and maintaining healthcare coverage and adequate reimbursement; ● the terms and timing of any additional collaboration, license or other arrangement, including the terms and timing of any payments thereunder; ● our ability to enforce and defend intellectual property rights and claims; and ● our ability to maintain continued acceptable safety profiles of our product candidates following approval.
We are also unable to predict when, if ever, we will be able to generate revenue from such product candidates due to the numerous risks and uncertainties associated with drug development, including the uncertainty of: • our ability to timely and successfully complete preclinical studies and clinical trials for BNC210 and other current or future product candidates; • the ability of our existing or future licensees and collaborators to successfully develop and commercialize product candidates pursuant to collaboration agreements, including Merck with respect to its two product candidates and Carina with respect to BNC101; • our successful initiation, enrollment in and completion of clinical trials for BNC210 and other current or future product candidates, including our ability to generate positive data from any such clinical trials; • our ability to demonstrate to the satisfaction of the FDA and comparable regulatory authorities the safety, efficacy, consistent manufacturing quality and acceptable risk-benefit profile of our product candidates for their intended uses; • our plans to submit NDAs to the FDA for BNC210 and future product candidates; • our ability to obtain in a timely manner necessary approvals or authorizations from applicable regulatory authorities; • the costs associated with the development of any additional development programs we identify in-house or acquire through collaborations or other arrangements; • our ability to establish manufacturing capabilities or make arrangements with third-party manufacturers for clinical supply and commercial manufacturing; • our ability to advance our early-stage CNS assets into IND-enabling studies either on our own or through collaborations; 46 • obtaining and maintaining patent and trade secret protection or regulatory exclusivity for our current and future product candidates; • launching commercial sales of our product candidates, if and when approved, whether alone or in collaboration with others; • obtaining and maintaining acceptance of our product candidates, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies; • obtaining and maintaining healthcare coverage and adequate reimbursement; • the terms and timing of any additional collaboration, license or other arrangement, including the terms and timing of any payments thereunder; • our ability to enforce and defend intellectual property rights and claims; and • our ability to maintain continued acceptable safety profiles of our product candidates following approval.
Any of these occurrences may harm our business, financial condition and prospects significantly. We have entered Phase 3 of our development efforts for BNC210 in SAD and are preparing to enter into Phase 3 of our development efforts for BNC210 in PTSD.
Any of these occurrences may harm our business, financial condition and prospects significantly. We have entered Phase 3 of our development efforts for BNC210 in SAD and are preparing to enter into Phase 2b/3 of our development efforts for BNC210 in PTSD.
This could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects. 93 In addition, while it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who, in fact, conceives or develops intellectual property that we regard as our own.
This could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects. 81 In addition, while it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who, in fact, conceives or develops intellectual property that we regard as our own.
Outside parties may: ● have staffing difficulties; ● fail to comply with contractual obligations; 66 ● experience regulatory compliance issues; and ● form relationships with other entities, some of which may be our competitors.
Outside parties may: • have staffing difficulties; • fail to comply with contractual obligations; • experience regulatory compliance issues; and • form relationships with other entities, some of which may be our competitors.
The results of preclinical studies and early clinical trials of our current and/or our other future product candidates, if any, including positive results, may not be predictive of the results of later-stage clinical trials.
Results of earlier clinical trials may not be predictive of the results of later-stage clinical trials. The results of preclinical studies and early clinical trials of our current and/or our other future product candidates, if any, including positive results, may not be predictive of the results of later-stage clinical trials.
We are dependent on MSD to provide us with any updates related to clinical trial results, serious adverse events and ongoing communications with the FDA and other regulatory agencies related to these programs, which MSD may provide or withhold in its sole discretion, and as a result we may not be able to provide material updates on a timely basis or at all with respect to these programs.
We are dependent on Merck to provide us with any updates related to clinical trial results, serious adverse events and ongoing communications with the FDA and other regulatory agencies related to these programs, which Merck may provide or withhold in its sole discretion, and as a result we may not be able to provide material updates on a timely basis or at all with respect to these programs.
We are an “emerging growth company,” as defined in the JOBS Act, and we take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act, reduced disclosure obligations regarding executive compensation in our periodic reports and any proxy statements, exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved.
We are an “emerging growth company,” as defined in the JOBS Act, and we take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act, reduced disclosure obligations regarding executive compensation in our periodic reports and any proxy statements, exemptions from the requirements of holding a non-binding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved.
The commencement and rate of completion of preclinical studies and clinical trials for a product candidate may be delayed by many factors, including, for example: ● timely completion of preclinical laboratory tests, animal studies and formulation studies in accordance with FDA’s good laboratory practice requirements and other applicable regulations; ● submission of an Investigational New Drug Application (“IND”) to the FDA and delays or failure in obtaining clearance thereof by the FDA; 49 ● delays or failure in obtaining approval by an independent Institutional Review Board (“IRB”) or ethics committee at each clinical site before each trial may be initiated; ● delays in reaching a consensus with regulatory agencies on study design and obtaining regulatory authorization to commence clinical trials; ● delays in reaching agreement on acceptable terms with prospective contract research organizations (“CROs”), and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; ● delays in identifying, contracting and training suitable clinical investigators; ● delays in manufacturing, testing, releasing, validating or importing/exporting sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing; ● insufficient or inadequate supply or quality of product candidates or other materials necessary for use in clinical trials, or delays in sufficiently developing, characterizing or controlling a manufacturing process suitable for clinical trials; ● imposition of a temporary or permanent clinical hold by regulatory authorities; ● developments on trials conducted by competitors for related technology that raises FDA or foreign regulatory authority concerns about risk to patients of the technology broadly, or if the FDA or a foreign regulatory authority finds that the investigational protocol or plan is deficient to meet its stated objectives; ● delays or failure in screening and enrolling suitable patients and delays or failure caused by patients withdrawing from clinical trials or failing to return for post-treatment follow-up; ● difficulties collaborating with patient groups and investigators; ● failure by our investigators and patients to adhere to clinical trial protocols; ● failure by our CROs, other third parties or us to manage the clinical trials according to the contracted terms and timelines; ● failure to perform clinical trials in accordance with the FDA’s good clinical practice requirements (“GCPs”), or applicable regulatory guidelines in other countries; ● occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits, or occurrence of adverse events in a trial of the same class of agents conducted by other companies; ● changes to the clinical trial protocols; ● clinical sites dropping out of a trial; ● changes in regulatory requirements and guidance including primary efficacy endpoints for approval that require amending or submitting new clinical protocols; ● changes in the standard of care on which a clinical development plan was based, which may require new or additional trials; ● selection of clinical endpoints that require prolonged periods of observation or analyses of resulting data; 50 ● the cost of clinical trials of our product candidates being greater than we anticipate; ● inability to generate sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation or continuation of clinical trials; ● clinical trials of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development of such product candidates; ● transfer of manufacturing processes to larger-scale facilities operated by a contract manufacturing organization (“CMO”), and delays or failure by our CMOs or us to make any necessary changes to such manufacturing process; and ● third parties being unwilling or unable to satisfy their contractual obligations to us.
The commencement and rate of completion of preclinical studies and clinical trials for a product candidate may be delayed by many factors, including, for example: • timely completion of preclinical laboratory tests, animal studies and formulation studies in accordance with FDA’s good laboratory practice requirements and other applicable regulations; • submission of an IND to the FDA and delays or failure in obtaining clearance thereof by the FDA; • delays or failure in obtaining approval by an independent IRB or ethics committee at each clinical site before each trial may be initiated; • delays in reaching a consensus with regulatory agencies on study design and obtaining regulatory authorization to commence clinical trials; • delays in reaching agreement on acceptable terms with prospective contract research organizations (“CROs”), and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; • delays in identifying, contracting and training suitable clinical investigators; • delays in manufacturing, testing, releasing, validating or importing/exporting sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing; • insufficient or inadequate supply or quality of product candidates or other materials necessary for use in clinical trials, or delays in sufficiently developing, characterizing or controlling a manufacturing process suitable for clinical trials; • imposition of a temporary or permanent clinical hold by regulatory authorities; • developments on trials conducted by competitors for related technology that raises FDA or foreign regulatory authority concerns about risk to patients of the technology broadly, or if the FDA or a foreign regulatory authority finds that the investigational protocol or plan is deficient to meet its stated objectives; • delays or failure in screening and enrolling suitable patients and delays or failure caused by patients withdrawing from clinical trials or failing to return for post-treatment follow-up; • difficulties collaborating with patient groups and investigators; • failure by our investigators and patients to adhere to clinical trial protocols; • failure by our CROs, other third parties or us to manage the clinical trials according to the contracted terms and timelines; • failure to perform clinical trials in accordance with the FDA’s good clinical practice requirements (“GCPs”), or applicable regulatory guidelines in other countries; • occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits, or occurrence of adverse events in a trial of the same class of agents conducted by other companies; • changes to the clinical trial protocols; • clinical sites dropping out of a trial; • changes in regulatory requirements and guidance including primary efficacy endpoints for approval that require amending or submitting new clinical protocols; 45 • changes in the standard of care on which a clinical development plan was based, which may require new or additional trials; • selection of clinical endpoints that require prolonged periods of observation or analyses of resulting data; • the cost of clinical trials of our product candidates being greater than we anticipate; • inability to generate sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation or continuation of clinical trials; • clinical trials of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development of such product candidates; • transfer of manufacturing processes to larger-scale facilities operated by a contract manufacturing organization (“CMO”), and delays or failure by our CMOs or us to make any necessary changes to such manufacturing process; and • third parties being unwilling or unable to satisfy their contractual obligations to us.
This assessment will need to include disclosure of any material weaknesses identified by our management in our internal control over financial reporting.
This assessment will need to include disclosure of any material weaknesses identified by our management in our 42 internal control over financial reporting.
If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting once that firm begins its Section 404 reviews, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our ADSs could decline, and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities.
If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting once that firm begins its Section 404 reviews, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities.
We will remain an emerging growth company until the earlier of (1) the last day of the fiscal year (a) following the fifth anniversary of the closing of our initial public offering, (b) in which we have total annual gross revenue of at least $1.07 billion or (c) in which we are deemed to be a large accelerated filer, which requires the market value of our ADSs that are held by non-affiliates to exceed $700 million as of the prior June 30 th , and (2) the date on which we have issued more than $1 billion in non-convertible debt during the prior three-year period.
We will remain an emerging growth company until the earlier of (1) the last day of the fiscal year (a) following the fifth anniversary of the closing of our initial public offering, (b) in which we have total annual gross revenue of at least $1.07 billion or (c) in which we are deemed to be a large accelerated filer, which requires the market value of our common stock shares that are held by non-affiliates to exceed $700 million as of the prior June 30 th , and (2) the date on which we have issued more than $1 billion in non-convertible debt during the prior three-year period.
Any payments we may receive in connection with certain milestones or royalties under the 2014 MSD License Agreement may differ materially from those described in this Annual Report, and there can be no assurance that we will receive any such payments at all.
Any payments we may receive in connection with certain milestones or royalties under the 2014 Merck License Agreement may differ materially from those described in this Annual Report, and there can be no assurance that we will receive any such payments at all.
Ifc we fail to obtain any required licenses or make any necessary changes to our products or technologies, we may have to withdraw existing products from the market or may be unable to commercialize one or more of our products. Further, competitors or third parties may infringe or otherwise violate our intellectual property.
If we fail to obtain any required licenses or make any necessary changes to our products or technologies, we may have to withdraw existing products from the market or may be unable to commercialize one or more of our products. Further, competitors or third parties may infringe or otherwise violate our intellectual property.
For example, the loss of clinical trial data from completed or any future ongoing clinical trials for any of our product candidates could result in delays in our regulatory approval efforts and the loss of research data could result in delays of our research and development efforts and it would be expensive to recover or reproduce the data.
Additionally, the loss of clinical trial data from completed or any future ongoing clinical trials for any of our product candidates could result in delays in our regulatory approval efforts and the loss of research data could result in delays of our research and development efforts and it would be expensive to recover or reproduce the data.
It is therefore uncertain whether any of our losses carried forward as of June 30, 2024 will be available to be carried forward and available to offset our assessable income, if any, in future periods. Inflation could adversely affect our business and results of operations.
It is therefore uncertain whether any of our losses carried forward as of June 30, 2025 will be available to be carried forward and available to offset our assessable income, if any, in future periods. Inflation could adversely affect our business and results of operations.
Our financial statements as of June 30, 2024 were prepared under the assumption that we will continue as a going concern for the next twelve months from the date of issuance of these financial statements.
Our financial statements as of June 30, 2025 were prepared under the assumption that we will continue as a going concern for the next twelve months from the date of issuance of these financial statements.
Under the 2014 MSD License Agreement, MSD is responsible for using commercially reasonable efforts to develop, file for marketing authorization for and, following receipt thereof, to commercialize at least one product thereunder.
Under the 2014 Merck License Agreement, Merck is responsible for using commercially reasonable efforts to develop, file for marketing authorization for and, following receipt thereof, to commercialize at least one product thereunder.
Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our business, financial condition and results of operations and the price of our ADSs. If we fail to meet the continued listing requirements of Nasdaq, it could result in a de-listing of our ADSs.
Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our business, financial condition and results of operations and the price of our common stock. If we fail to meet the continued listing requirements of Nasdaq, it could result in a de-listing of our Common Stock.
If we raise funds through future collaborations, licenses and other similar arrangements, we may have to relinquish valuable rights to our future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us and/or that may reduce the value of our ADSs.
If we raise funds through future collaborations, licenses and other similar arrangements, we may have to relinquish valuable rights to our future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us and/or that may reduce the value of our common stock.
If no analysts cover us or if one or more analysts cease to cover us or fail to publish reports in a regular manner, we could lose visibility in the financial markets, which could cause a significant and prolonged decline in the trading price of our ADSs due to lack of investor awareness.
If no analysts cover us or if one or more analysts cease to cover us or fail to publish reports in a regular manner, we could lose visibility in the financial markets, which could cause a significant and prolonged decline in the trading price of our common stock due to lack of investor awareness.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, investors’ ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect investors’ rights as a holder of our ADSs.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, investors’ ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect investors’ rights as a holder of our common stock.
There is no guarantee that equity research organizations will elect to initiate or sustain research coverage of us, nor whether such research, if initiated, will be positive towards the trading price of our ADSs or our business, financial condition, results of operations and prospects.
There is no guarantee that equity research organizations will elect to initiate or sustain research coverage of us, nor whether such research, if initiated, will be positive towards the trading price of our common stock or our business, financial condition, results of operations and prospects.
Clinical trials can be halted or delayed for a variety of reasons, including those related to: ● side effects or adverse events in study participants presenting an unacceptable safety risk; ● inability to reach agreements with prospective third-party CROs and clinical trial sites, or the breach of such agreements; ● failure of third-party contractors, such as third-party CROs, or investigators to comply with regulatory requirements; ● delay or failure in obtaining the necessary approvals from regulators or IRBs or ethics committees in order to commence a clinical trial at a prospective trial site, or their suspension or termination of a clinical trial once commenced; ● a requirement to undertake and complete additional preclinical studies to generate data required to support the submission of an NDA or a Biologics License Application (“BLA”); ● difficulty in having patients complete a trial or return for post-treatment follow-up; ● clinical sites deviating from trial protocol or dropping out of a trial; ● problems with Active Pharmaceutical Ingredient (“API”) or drug product stability or shelf-life, storage and distribution; ● adding new clinical trial sites; ● our inability to manufacture, or obtain from third parties, adequate supply of API or drug product to complete our preclinical studies and clinical trials; ● the impact of the prior COVID-19 or any future pandemic on our future clinical trials, including any enrollment delays; and ● governmental or regulatory delays and changes in regulatory requirements, policy and guidelines.
Even if our clinical trials are completed, the results may not be sufficient to obtain regulatory approval for our product candidates. 55 Clinical trials can be halted or delayed for a variety of reasons, including those related to: • side effects or adverse events in study participants presenting an unacceptable safety risk; • inability to reach agreements with prospective third-party CROs and clinical trial sites, or the breach of such agreements; • failure of third-party contractors, such as third-party CROs, or investigators to comply with regulatory requirements; • delay or failure in obtaining the necessary approvals from regulators, IRBs, or ethics committees to commence a clinical trial at a prospective trial site, or their suspension or termination of a clinical trial once commenced; • a requirement to undertake and complete additional preclinical studies to generate data required to support the submission of an NDA or a Biologics License Application (“BLA”); • difficulty in having patients complete a trial or return for post-treatment follow-up; • clinical sites deviating from trial protocol or dropping out of a trial; • problems with Active Pharmaceutical Ingredient (“API”) or drug product stability or shelf-life, storage and distribution; • adding new clinical trial sites; • our inability to manufacture, or obtain from third parties, adequate supply of API or drug product to complete our preclinical studies and clinical trials; • the impact of the prior COVID-19 or any future pandemic on our future clinical trials, including any enrollment delays; and • governmental or regulatory delays and changes in regulatory requirements, policy and guidelines.
We cannot predict if investors will find our ADSs less attractive because we rely on these exemptions. If some investors find our ADSs less attractive as a result, there may be a less active trading market for our ADSs and the trading price of our ADSs may be more volatile.
We cannot predict if investors will find our common stock less attractive because we rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and the trading price of our common stock may be more volatile.
In the event that we do not obtain analyst coverage, or if one or more of the analysts downgrade our ADSs or comment negatively about our prospects or the prospects of other companies operating in our industry, the trading price of our ADSs could decline significantly.
In the event that we do not obtain analyst coverage, or if one or more of the analysts downgrade our common stock or comment negatively about our prospects or the prospects of other companies operating in our industry, the trading price of our common stock could decline significantly.
We currently carry clinical trial liability insurance in the amount of A$20.0 million in the aggregate, but there can be no assurance that we will be able to maintain such insurance or that the amount of such insurance will be adequate to cover claims.
We currently carry clinical trial liability insurance in the amount of $10.0 million in the aggregate, but there can be no assurance that we will be able to maintain such insurance or that the amount of such insurance will be adequate to cover claims.
We are an “emerging growth company” (as defined in the JOBS Act) and as a result of the reduced disclosure and governance requirements applicable to emerging growth companies, our ADSs may be less attractive to investors.
We are an “emerging growth company” (as defined in the JOBS Act) and as a result of the reduced disclosure and governance requirements applicable to emerging growth companies, our common stock may be less attractive to investors.
As a U.S. public reporting company, we are required to maintain effective internal control over financial reporting suitable to prepare our publicly reported financial statements in a timely and accurate manner. Pursuant to Section 404 of Sarbanes-Oxley, our management is required to report upon the effectiveness of our internal control over financial reporting beginning with this annual report.
As a U.S. public reporting company, we are required to maintain effective internal control over financial reporting suitable to prepare our publicly reported financial statements in a timely and accurate manner. Pursuant to Section 404 of Sarbanes-Oxley, our management is required to report upon the effectiveness of our internal control over financial reporting.
These broad market fluctuations as well a broad range of other factors, including the realization of any of the risks described in this “Risk Factors” section of this Annual Report, may cause the market price of our ADSs to decline.
These broad market fluctuations as well a broad range of other factors, including the realization of any of the risks described in the “Risk Factors” section of this Annual Report, may cause the market price of our common stock to decline.
The trading price of our ADSs on the Nasdaq Global Market has been highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control.
The trading price of our common stock on the Nasdaq Global Market has been highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control.
If our revenue or operating results fall below the expectations of analysts or investors or below any guidelines we may provide to the market, or if the guidelines we provide to the market are below the expectations of analysts or investors, this could adversely affect the trading price of our ADSs.
If our revenue or operating results fall below the expectations of analysts or investors or below any guidelines we may provide to the market, or if the guidelines we provide to the market are below the expectations of analysts or investors, this could adversely affect the trading price of our common stock.
In addition, the stock markets in general, and the markets for biotechnology and pharmaceutical stocks in particular, have experienced extreme volatility that may have been unrelated to the operating performance of the issuer. These broad market fluctuations may adversely affect the trading price or liquidity of our ordinary shares or ADSs.
In addition, the stock markets in general, and the markets for biotechnology and pharmaceutical stocks in particular, have experienced extreme volatility that may have been unrelated to the operating performance of the issuer. These broad market fluctuations may adversely affect the trading price or liquidity of our common stock.
If we fail to satisfy the continued listing requirements of Nasdaq, such as the corporate governance requirements, continued listing requirements such as the minimum $1.00 closing bid price requirement, Nasdaq could take steps to delist our ADSs.
If we fail to satisfy the continued listing requirements of Nasdaq, such as the corporate governance requirements, continued listing requirements such as the minimum $1.00 closing bid price requirement, Nasdaq could take steps to delist our common stock.
In addition, Sarbanes-Oxley Act, along with rules promulgated by the SEC, and Nasdaq, where our ADSs trade, have significant requirements on public companies, including many changes involving corporate governance. Management and other company personnel devote a substantial amount of time ensuring our compliance with these regulations.
In addition, Sarbanes-Oxley Act, along with rules promulgated by the SEC, and Nasdaq, where our common stock trades, have significant requirements on public companies, including many changes involving corporate governance. Management and other company personnel devote a substantial amount of time ensuring our compliance with these regulations.
If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, possible exclusion from participation in Medicare, Medicaid and other U.S. federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations. 81 Healthcare legislative reform measures may have a material adverse effect on our business and results of operations.
If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, possible exclusion from participation in Medicare, Medicaid and other U.S. federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
Raising additional capital may cause dilution to our shareholders, including holders of our ADSs, restrict our operations or require us to relinquish rights to our technologies or product candidates.
Raising additional capital may cause dilution to our shareholders, including holders of our common stock, restrict our operations, or require us to relinquish rights to our technologies or product candidates.
If we are unable to raise capital or find alternative sources of financing when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs, clinical trials or any future commercialization efforts. We had cash and cash equivalents of $12.6 million as of June 30, 2024.
If we are unable to raise capital or find alternative sources of financing when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs, clinical trials or any future commercialization efforts. We had cash and cash equivalents of $14.2 million as of June 30, 2025.
Our failure to do so could adversely affect our business, financial condition, results of operations and prospects, and the trading price of our ADSs may decline.
Our failure to do so could adversely affect our business, financial condition, results of operations and prospects, and the trading price of our common stock may decline.
Any failure by us to comply with Nasdaq’s continued listing standards could result in a deficiency notice and, if not cured within the applicable period, could result in delisting. Our ADSs are currently listed on the Nasdaq Global Market.
Any failure by us to comply with Nasdaq’s continued listing standards could result in a deficiency notice and, if not cured within the applicable period, could result in delisting. Our shares of common stock are currently listed on the Nasdaq Global Market.
Further, collaborations involving our technologies or current or future product candidates are subject to numerous risks, which may include the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; ● collaborators may not pursue development and commercialization of our current or future product candidates or may elect not to continue or renew development or commercialization of our current or future product candidates based on clinical trial results, changes in their strategic focus due to the acquisition of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our current or future product candidates; ● a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to their marketing and distribution; ● collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; ● disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our current or future product candidates, or that result in costly litigation or arbitration that diverts management attention and resources; ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable current or future product candidates; ● collaborators may own or co-own intellectual property covering our products that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property; and ● collaborators may not pay milestones and royalties due to the company in a timely manner. 69 As a result, we may not be able to realize the benefit of our existing collaboration and licensing arrangements or any future strategic partnerships or acquisitions, collaborations or license arrangements we may enter into if we are unable to successfully integrate them with our existing operations and company culture, which could delay our timelines or otherwise adversely affect our business.
Further, collaborations involving our technologies or current or future product candidates are subject to numerous risks, which may include the following: • collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; • collaborators may not pursue development and commercialization of our current or future product candidates or may elect not to continue or renew development or commercialization of our current or future product candidates based on clinical trial results, changes in their strategic focus due to the acquisition of competitive products, availability of funding or other external factors, such as a business combination that diverts resources or creates competing priorities; 61 • collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our current or future product candidates • a collaborator with marketing and distribution rights to one or more products may not commit sufficient resources to their marketing and distribution; • collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; • disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our current or future product candidates, or that result in costly litigation or arbitration that diverts management attention and resources • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable current or future product candidates; • collaborators may own or co-own intellectual property covering our products that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property; and • collaborators may not pay milestones and royalties due to the company in a timely manner.
The financial markets and the global economy may also be adversely affected by the current or anticipated impact of military conflict, including the conflict between Russia and Ukraine, terrorism or other geopolitical events.
The financial markets and the global economy may also be adversely affected by the current or anticipated impact of military conflict, including the conflict between Russia and Ukraine, conflicts in the Middle East, terrorism or other geopolitical events.
Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and results of operations and the price of our ADSs.
Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and results of operations and the price of our common stock.
Our total accumulated deficit was $177.7 million for the fiscal year ended June 30, 2024. Substantially all our losses have resulted from expenses incurred in connection with our research and development programs, preclinical studies, clinical trials and from general and administrative costs associated with our operations.
Our total accumulated deficit was $178.3 million for the fiscal year ended June 30, 2025. Substantially all our losses have resulted from expenses incurred in connection with our research and development programs, preclinical studies, clinical trials and from general and administrative costs associated with our operations.
These factors include those discussed in this “Risk Factors” section of this Annual Report and positive, negative or unexpected developments relating to: ● results from, or any delays in, clinical trial programs relating to our product candidates; ● our ability to obtain regulatory approval for our product candidates, or delays in obtaining such approval; ● our ability to commercialize any future drugs, or delays in commercializing such drugs; ● announcements of regulatory approval or a complete response letter to our product candidates, or specific label indications or patient populations for its use, or changes or delays in the regulatory review process; ● announcements relating to future collaborations or our existing collaborations, including decisions regarding the exercise by our collaboration partners of their options, if any, or any termination by them of their collaborations with us; ● the timing and amount of payments to us under our collaborations, if any; ● announcements of therapeutic innovations or new drugs by us or our competitors; ● announcements regarding the parent drugs that we use in developing our product candidates; ● actions taken by regulatory authorities with respect to our clinical trials, manufacturing supply chain or sales and marketing activities; ● changes or developments in laws or regulations applicable to our product candidates; ● any changes to our relationship with any manufacturers or suppliers; ● the success of our testing and clinical trials; ● the success of our efforts to acquire or license or discover additional product candidates; ● any intellectual property infringement actions in which we may become involved; ● announcements concerning our competitors or the pharmaceutical industry in general; ● achievement of expected drug sales and profitability; ● manufacture, supply or distribution shortages; ● actual or anticipated fluctuations in our operating results; ● the FDA, EMA or other similar regulatory actions affecting us or our industry or other healthcare reform measures in the United States or elsewhere; ● changes in financial estimates or recommendations by securities analysts; ● trading volume of the ADSs; ● sales of our ADSs by us, our senior management and directors or our shareholders in the future; ● general economic and market conditions and overall fluctuations in the equity markets; and ● the loss of any of our key scientific or senior management personnel.
These factors include but are not limited to the “Risk Factors” noted below and as set forth in our Annual Report and positive, negative or unexpected developments relating to: • results from, or any delays in, clinical trial programs relating to our product candidates; • our ability to obtain regulatory approval for our product candidates, or delays in obtaining such approval; • our ability to commercialize any future drugs, or delays in commercializing such drugs; • announcements of regulatory approval or a complete response letter to our product candidates, or specific label indications or patient populations for its use, or changes or delays in the regulatory review process; • the timing and amount of payments to us under our collaborations, if any; • announcements of therapeutic innovations or new drugs by us or our competitors; • announcements regarding the parent drugs that we use in developing our product candidates; • actions taken by regulatory authorities with respect to our clinical trials, manufacturing supply chain or sales and marketing activities; • changes or developments in laws or regulations applicable to our product candidates; • any changes to our relationship with any manufacturers or suppliers; • the success of our testing and clinical trials;the success of our efforts to acquire or license or discover additional product candidates; • any intellectual property infringement actions in which we may become involved; • announcements concerning our competitors or the pharmaceutical industry in general; • achievement of expected drug sales and profitability; • manufacture, supply or distribution shortages; • actual or anticipated fluctuations in our operating results; • the FDA, EMA or other similar regulatory actions affecting us or our industry or other healthcare reform measures in the United States or elsewhere; • changes in financial estimates or recommendations by securities analysts; • trading volume of our common stock; • sales of our common stock or other securities by us, our senior management and directors or our shareholders in the future; • general economic and market conditions and overall fluctuations in the equity markets; and • the loss of any of our key scientific or senior management personnel.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Board of Directors Oversight The Audit & Risk Management Committee is central to the Board’s oversight of cybersecurity risks and bears the primary responsibility for this domain. The Audit & Risk Management Committee is composed of board members with diverse expertise including risk management, technology, and finance, equipping them to oversee cybersecurity risks effectively.
Governance Board of Directors Oversight The Audit & Risk Management Committee is central to the Board’s oversight of cybersecurity risks and bears the primary responsibility for this domain. The Audit & Risk Management Committee is composed of board members with diverse expertise including risk management, technology, and finance, equipping them to oversee cybersecurity risks effectively.
Risk Management Personnel Our IT Manager is actively involved in assessing, monitoring and managing our cybersecurity risks. He has 30 years of experience in the field of cybersecurity, and his in-depth knowledge and experience are instrumental in developing and executing our cybersecurity strategies.
Risk Management Personnel Our IT Manager is actively involved in assessing, monitoring and managing our cybersecurity risks. He has over 30 years of experience in the field of cybersecurity, and his in-depth knowledge and experience are instrumental in developing and executing our cybersecurity strategies.
Furthermore, significant cybersecurity matters and strategic risk management decisions are escalated to the Board of Directors, ensuring that they have comprehensive oversight and can provide guidance on critical cybersecurity issues.
Furthermore, significant cybersecurity matters and strategic risk management decisions are escalated to the Board of Directors, ensuring that they have comprehensive oversight and can provide guidance on critical cybersecurity issues. 84
These partnerships will enable us to leverage specialized knowledge and insights, ensuring our cybersecurity strategies and processes remain at the forefront of industry best practices. Oversee Third-party Risk Because we are aware of the risks associated with third-party service providers, Bionomics will implement stringent processes to oversee and manage these risks.
These partnerships will enable us to leverage specialized knowledge and insights, ensuring our cybersecurity strategies and processes remain at the forefront of industry best practices. Oversee Third-party Risk Because we are aware of the risks associated with third-party service providers, Neuphoria will implement stringent processes to oversee and manage these risks.
Reporting to Board of Directors Our IT Manager will provide regular updates to our CEO, Spyros Papapetropoulos, regarding all aspects related to cybersecurity risks and incidents. This ensures that the highest levels of management are kept abreast of the cybersecurity posture and potential risks faced by Bionomics.
Reporting to Management and the Board of Directors Our IT Manager will provide regular updates to our CEO, Spyros Papapetropoulos, regarding all aspects related to cybersecurity risks and incidents. This ensures that the highest levels of management are kept abreast of the cybersecurity posture and potential risks faced by Neuphoria.
Item 1C. Cybersecurity Risk management and strategy Bionomics recognizes the critical importance of developing, implementing, and maintaining robust cybersecurity measures to safeguard our information systems and protect the confidentiality, integrity and availability of our data.
Item 1C. C ybersecurity. Risk management and strategy Neuphoria recognizes the critical importance of developing, implementing, and maintaining robust cybersecurity measures to safeguard our information systems and protect the confidentiality, integrity and availability of our data.
Engage Third-parties on Risk Management Recognizing the complexity and evolving nature of cybersecurity threats, Bionomics has started negotiating and engaging with a range of external experts, including cybersecurity assessors, consultants, and auditors in evaluating and testing our risk management systems.
Engage Third-parties on Risk Management Recognizing the complexity and evolving nature of cybersecurity threats, Neuphoria has and engaged with a range of external experts, including cybersecurity assessors, consultants, advisors, and auditors in evaluating and testing our risk management systems.
Risks from Cybersecurity Threats We have not encountered cybersecurity challenges that have materially impaired our operations or financial standing. 106 Governance The Board of Directors is acutely aware of the critical nature of managing risks associated with cybersecurity threats.
Risks from Cybersecurity Threats While we have encountered cybersecurity threats, including a breach of an administrative email account, these challenges have not resulted in the loss of any data, materials, or clinical information, and have not materially impaired our operations or financial standing.
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The Board will form a risk management team led by Tim Cunningham, our CFO, to establish robust oversight mechanisms to ensure effective governance in managing risks associated with cybersecurity threats because we recognize the significance of these threats to our operational integrity and stakeholder confidence.
Removed
Management’s Role in Managing Risk Our CFO plays a pivotal role in informing the Audit & Risk Management Committee on cybersecurity risks. He will provide the latest developments in cybersecurity to the Audit & Risk Management Committee on a regular basis, with a minimum frequency of once per year.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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From time to time, we may become involved in legal proceedings relating to claims arising from the ordinary course of business. We intend to defend vigorously against any future claims and litigation.
From time to time, we may become involved in legal proceedings relating to claims arising from the ordinary course of business. We intend to defend vigorously against any future claims and litigation. Item 4. Mi ne Safety Disclosures. Not applicable. 85 PAR T II
Item 3. Legal Proceedings Our management believes that there are currently no formal claims or actions pending against us, the ultimate disposition of which could have a material adverse effect on our results of operations, financial condition or cash flows.
Item 3. Le gal Proceedings. Our management is not aware of any current formal claims or actions pending against us, the ultimate disposition of which could have a material adverse effect on our results of operations, financial condition or cash flows.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Any future determination to declare cash dividends will be made at the discretion of our board of directors and will depend on our financial condition, results of operations, capital requirements, general business conditions and other factors that our board of directors may deem relevant. In the fiscal year ended June 30, 2024, we did not declare or pay any dividends.
Any future determination to declare cash dividends will be made at the discretion of our board of directors and will depend on our financial condition, results of operations, capital requirements, general business conditions and other factors that our board of directors may deem relevant. In the fiscal year ended June 30, 2025, we did not declare or pay any dividends.
This number is not representative of the number of beneficial holders of our shares or ADRs nor are they representative of where such beneficial holders reside, as many of these ordinary shares and ADRs were held of record by brokers or other nominees.
This number is not representative of the number of beneficial holders of our shares or common stock nor are they representative of where such beneficial holders reside, as many of these ordinary shares and common stock were held of record by brokers or other nominees.
Dividends We have not paid cash dividends on our ordinary shares to date, and we intend to retain all available funds and any future earnings for use in the operation of our business. We do not anticipate paying any cash dividends on our ordinary shares in the foreseeable future.
Dividends We have not paid cash dividends on our shares of common stock, or previously on ordinary shares or ADSs, to date, and we intend to retain all available funds and any future earnings for use in the operation of our business. We do not anticipate paying any cash dividends on our common stock in the foreseeable future.
Prior to delisting from the Australian Securities Exchange in August 2023, our ordinary shares had traded on the ASX under the symbol “BNO” since 1999. As of June 30, 2024, there were 3,500 holders on record of our ordinary shares.
Prior to delisting from the ASX in August 2023, our ordinary shares were publicly traded on the Australian Securities Exchange under the symbol “BNO”. As of June 30, 2025, there were 3,122 holders on record of our ordinary shares.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities Our ADSs commenced trading on the Nasdaq Global Market on December 17, 2021 under the symbol “BNOX” and continue to do so. Prior to this, no public market existed in the United States for our ADSs.
Item 5. Market for Registrant’s Common Equity, Re lated shareholder Matters and Issuer Purchases of Equity Securities. Our ADSs commenced trading on the Nasdaq Global Market on December 17, 2021 under the symbol “BNOX” and continued to do so until December 23, 2024, the date prior to the effectiveness of our redomiciliation as a U.S. domestic company.
Removed
Securities Authorized for Issuance Under Equity Compensation Plans The information included under Item 12 of Part III of this Report, “Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters,” is hereby incorporated by reference into this Item 5 of Part II of this Report.
Added
Beginning on December 24, 2024, Neuphoria’s shares of common stock began trading on the Nasdaq Global Market under the trading symbol "NEUP". Prior to this, no public market existed in the United States for our ADSs or other securities.
Removed
Recent Sales of Unregistered Securities On May 31, 2024, Bionomics entered into a Securities Purchase Agreement (the “Securities Purchase Agreement”) with an institutional accredited investor (the “Investor”), pursuant to which we agreed to issue and sell in a three tranche offering to the Investor of unregistered American Depositary Shares (“ADSs”, with each ADS representing 180 ordinary shares of Bionomics) (or pre-funded warrants to purchase ADSs (the “Pre-Funded Warrants”) in lieu thereof), and an accompanying five year cash purchase warrant (the “Accompanying Warrant”, issuable only in tranche 1) (together, the “Warrants”).
Added
Purchases of Equity Securities by the Issuer and Affiliated Purchasers None. Item 6. [Reserved] 86
Removed
This private placement was exempt from registration under the Securities Act in reliance on Section 4(a)(2).
Removed
The first tranche of the private placement consisted of 1,296,486 ADSs and 6,279,905 Pre-Funded Warrants, at a combined purchase price of $0.99 per ADS and Accompanying Warrant (or $0.9899 per Pre-Funded Warrant and Accompanying Warrant, which was sold at the purchase price of $0.99 per ADS and Accompanying Warrant, minus $0.0001 for the exercise price of each Pre-Funded Warrant) (the “Initial Purchase Price”), and the Accompanying Warrant to purchase up to 12,652,572 ADSs at an exercise price of $0.99 per ADS (or pre-funded warrants in lieu thereof) at the Initial Purchase Price per ADS (or pre-funded warrant in lieu thereof).
Removed
The first tranche of the private placement closed on June 3, 2024, resulting in aggregate gross proceeds of $7.5 million. 108 The second tranche of the private placement is subject to the satisfaction of regulatory milestones that, if achieved, would involve the purchase by Armistice of up to an additional US$25.0 million of ADSs (or pre-funded warrants in lieu thereof) from Bionomics at US$0.99 per ADS.
Removed
The second tranche milestones are the earlier of (i) receipt of formal written correspondence by Bionomics from the FDA following planned interactions with the FDA regarding the outcomes of the end-of-phase meeting 2 and breakthrough designation status for BNC210 for PTSD or (ii) December 31, 2024.
Removed
In September 2024, the FDA rejected our initial application for breakthrough designation and, as a result, we believe it is unlikely that the second tranche will be exercised by or before its expiration on January 31, 2025.
Removed
The third tranche of the private placement is subject to the satisfaction of regulatory milestones that, if achieved, would involve the purchase by Armistice of up to an additional US$25.0 million of ADSs (or pre-funded warrants in lieu thereof) from Bionomics at US$0.99 per ADS.
Removed
The third tranche milestones are the latter of (i) completion of an interim blinded safety review of the planned BNC210 Phase-3 PTSD study or (ii) December 31, 2025. The exercise of the third tranche is dependent on our ability to fund the planned Phase-3 PTSD study.
Removed
The Pre-Funded Warrant issued in the first tranche is immediately exercisable and remains exercisable until exercised in full. The Accompanying Warrant issued in the first tranche is immediately exercisable and remains exercisable until June 2, 2029.
Removed
However, Armistice may not exercise the Accompanying Warrant to the extent such exercise would cause it to beneficially own a number of ordinary shares that would exceed 4.99% of our then outstanding ordinary shares following such exercise.
Removed
The net proceeds from the private placement will be used to fund the advancement of our clinical development pipeline, business development activities, research and development, working capital and general corporate purposes.
Removed
Concurrently with the entry into the Securities Purchase Agreement, Bionomics entered into a registration rights agreement with the Investor for the registration for resale by the Investor of the ADSs and the Warrant Shares.
Removed
We filed with the SEC a registration statement on Form F-1 relating to the securities issued in the first tranche, which was declared effective on June 26, 2024. Purchases of Equity Securities by the Issuer and Affiliated Purchasers None.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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We are advancing our lead product candidate, BNC210, an oral, proprietary, selective NAM of the α7 receptor, for the chronic treatment of Post-Traumatic Stress Disorder (“PTSD”) and the acute treatment of Social Anxiety Disorder (“SAD”). There remains a significant unmet medical need for the over 27 million patients in the United States alone suffering from SAD and PTSD.
We are advancing our lead product candidate, BNC210, an oral, proprietary, selective NAM of the α7 receptor, for the the acute treatment of Social Anxiety Disorder (“SAD”) and chronic treatment of Post-Traumatic Stress Disorder (“PTSD”). There remains a significant unmet medical need for the over 27 million patients in the United States alone suffering from SAD and PTSD.
The duration, costs, and timing of preclinical studies and clinical trials and development of our product candidates will depend on a variety of factors, including: ● successful completion of our planned Phase 3 clinical trials in SAD and PTSD; ● successful completion of preclinical studies and of clinical trials for BNC210 and our other current product candidates and any future product candidates; ● data from our clinical programs that support an acceptable risk-benefit profile of our product candidates in the intended patient populations; ● acceptance by the FDA, regulatory authorities in Europe, or other regulatory agencies, of the IND applications, clinical trial applications and/or other regulatory filings for BNC210, our other current product candidates and any future product candidates; ● expansion and maintenance of a workforce of experienced scientists and others to continue to develop our product candidates; ● successful application for and receipt of marketing approvals from applicable regulatory authorities; ● obtainment and maintenance of regulatory exclusivity for our product candidates; ● arrangements with third-party manufacturers for, or establishment of, commercial manufacturing capabilities; ● establishment of sales, marketing and distribution capabilities and successful launch of commercial sales of our products, if and when approved, whether alone or in collaboration with others; 112 ● acceptance of our products, if and when approved, by patients, the medical community and third-party payors; ● effective competition with other therapies; ● obtainment and maintenance of coverage, adequate pricing and adequate reimbursement from third-party payors, including government payors; ● obtainment, maintenance, enforcement, defense and protection of our rights in our intellectual property portfolio; ● avoidance of infringement, misappropriation or other violations with respect to others’ intellectual property or proprietary rights; and ● maintenance of a continued acceptable safety profile of our products following receipt of any marketing approvals.
The duration, costs, and timing of preclinical studies and clinical trials and development of our product candidates will depend on a variety of factors, including: • successful completion of our planned Phase 3 clinical trials in SAD and PTSD. • successful completion of preclinical studies and of clinical trials for BNC210 and our other current product candidates and any future product candidates; • data from our clinical programs that support an acceptable risk-benefit profile of our product candidates in the intended patient populations; • acceptance by the FDA, regulatory authorities in Europe, or other regulatory agencies, of the IND applications, clinical trial applications and/or other regulatory filings for BNC210, our other current product candidates and any future product candidates; • expansion and maintenance of a workforce of experienced scientists and others to continue to develop our product candidates; 89 • successful application for and receipt of marketing approvals from applicable regulatory authorities; • obtainment and maintenance of regulatory exclusivity for our product candidates; • arrangements with third-party manufacturers for, or establishment of, commercial manufacturing capabilities; • establishment of sales, marketing and distribution capabilities and successful launch of commercial sales of our products, if and when approved, whether alone or in collaboration with others; • acceptance of our products, if and when approved, by patients, the medical community and third-party payors; • effective competition with other therapies; • obtainment and maintenance of coverage, adequate pricing and adequate reimbursement from third-party payors, including government payors; • obtainment, maintenance, enforcement, defense and protection of our rights in our intellectual property portfolio; • avoidance of infringement, misappropriation or other violations with respect to others’ intellectual property or proprietary rights; and • maintenance of a continued acceptable safety profile of our products following receipt of any marketing approvals.
General and Administration Expenses We expect our general and administration expenses to increase over the next several years to support expanded research and development activities and operating as a U.S. public company, including costs of additional personnel, increased costs related to additional investor relations activities, director and officer insurance premiums, and increased fees to outside consultants, lawyers, and accountants.
General and Administrative Expenses We expect our general and administration expenses to increase over the next several years to support expanded research and development activities and operating as a U.S. public company, including costs of additional personnel, increased costs related to investor relations activities, director and officer insurance premiums, and increased fees to outside consultants, lawyers, and accountants.
Royalties are payable until the later of expiration of all licensed patents covering the licensed products, or expiration of all data exclusivity with respect to the licensed product. If Carina Biotech enters into one or more sublicensing agreements relating to the licensed product, we are eligible to receive a percentage of sublicensing revenues.
Royalties are payable until the later of expiration of all licensed patents covering the licensed products, or expiration of all data exclusivity with respect to the licensed product. If Carina enters into one or more sublicensing agreements relating to the licensed product, we are eligible to receive a percentage of sublicensing revenues.
Carina Biotech is also obligated to pay us royalties on its net sales of licensed products, on a country-by-country and product-by-product basis, ranging from the low single digits to the mid-single digits, subject to certain specified deductions.
Carina is also obligated to pay us royalties on its net sales of licensed products, on a country-by-country and product-by-product basis, ranging from the low single digits to the mid-single digits, subject to certain specified deductions.
In May 2024, we entered into a Securities Purchase Agreement with Armistice Capital Master Fund Ltd. pursuant to which Bionomics agreed to issue and sell in a three-tranche private placement a certain number of restricted ADSs, a pre-funded warrant to purchase ADSs and an accompanying 5-year cash purchase warrant.
In May 2024, we entered into a Securities Purchase Agreement with Armistice Capital Master Fund Ltd. pursuant to which the Company agreed to issue and sell in a three-tranche private placement a certain number of restricted ADSs, a pre-funded warrant to purchase ADSs and an accompanying 5-year cash purchase warrant.
In addition, through a long-standing strategic partnership with Merck & Co., Inc., in the United States and Canada (“MSD”), we are also developing positive allosteric modulators (“PAMs”) of the α7 receptor to treat cognitive dysfunction. Bionomics’ pipeline also includes preclinical assets that target Kv3.1/3.2 and Nav1.7/1.8 ion channels being developed for CNS conditions of high unmet need.
In addition, through a long-standing strategic partnership with Merck & Co., Inc., in the United States and Canada (“Merck”), we are also developing positive allosteric modulators (“PAMs”) of the α7 receptor to treat cognitive dysfunction. Neuphoria's pipeline also includes preclinical assets that target Kv3.1/3.2 ion channels being developed for CNS conditions of high unmet need.
Off-Balance Sheet Arrangements We did not have during fiscal year 2024, and we do not currently have, any off-balance sheet financing arrangements or any relationships with unconsolidated entities or financial partnerships, including entities sometimes referred to as structured finance or special purpose entities, that were established for the purpose of facilitating off-balance sheet arrangements or other contractually narrow or limited purposes.
Off-Balance Sheet Arrangements We did not have during the period presented, and we do not currently have, any off-balance sheet financing arrangements or any relationships with unconsolidated entities or financial partnerships, including entities sometimes referred to as structured finance or special purpose entities, that were established for the purpose of facilitating off-balance sheet arrangements or other contractually narrow or limited purposes.
A substantial portion of our operating expenses and other income, if any, are denominated in the Australian dollar. During the years ended June 30, 2024 and 2023, we managed our exchange rate exposure principally by maintaining foreign currency cash accounts and managing our payments from the most appropriate accounts.
A substantial portion of our operating expenses and other income, if any, are denominated in the Australian dollar. During the twelve months ended June 30, 2025 and 2024, we managed our exchange rate exposure principally by maintaining foreign currency cash accounts and managing our payments from the most appropriate accounts.
Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our trade and other payables. We expect to continue to incur net losses for the foreseeable future, and we expect our research and development expenses, and our administrative and other expenses will continue to increase.
Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our accounts payable and accrued expenses. We expect to continue to incur net losses for the foreseeable future, and we expect our research and development expenses, and our administrative and other expenses will continue to increase.
From time to time, we may additionally use forward exchange contracts in an effort to manage certain foreign exchange rate exposures when appropriate. There were no foreign exchange contracts used during the years ended June 30, 2024, and 2023, respectively. See “Quantitative and Qualitative Disclosures about Market Risk” for more information.
From time to time, we may additionally use forward exchange contracts in an effort to manage certain foreign exchange rate exposures when appropriate. There were no foreign exchange contracts used during the twelve months ended June 30, 2025 and 2024. See “Quantitative and Qualitative Disclosures About Market Risk” for more information.
The sole obligation to Ironwood is to pay Ironwood low to mid-single digit royalties on the net sales of BNC210, if commercialized. In June 2014, we entered the 2014 MSD License Agreement to develop compounds targeting cognitive dysfunction associated with Alzheimer’s disease and other central nervous system conditions.
The sole obligation to Ironwood is to pay Ironwood low to mid-single digit royalties on the net sales of BNC210, if commercialized. In September 2014, we entered the 2014 Merck Research Collaboration and License Agreement to develop compounds targeting cognitive dysfunction associated with Alzheimer’s disease and other central nervous system conditions.
Pursuant to the Carina Biotech License, we are eligible to receive approximately $3 million in certain development, regulatory milestone payments if Carina Biotech advances the development of the therapy to a Phase 3 trial.
Pursuant to the Carina Biotech License, we are eligible to receive approximately $75.8 in certain development and regulatory milestone payments if Carina advances the development of the therapy to a Phase 3 trial.
Substantially all our direct research and development expenses in the years ended June 30, 2024 and 2023 were on BNC210 and consisted primarily of external costs, such as consultants, CMOs that conduct research and development activities on our behalf, costs related to production of preclinical and clinical materials, including fees paid to CMOs, and laboratory and vendor expenses related to the execution of our ongoing and planned preclinical studies and clinical trials.
Substantially all our direct research and development expenses during the twelve months ended June 30, 2025 and 2024 were on BNC210 and consisted primarily of external costs, such as consultants, CROs that conduct research and development activities on our behalf, costs related to production of preclinical and clinical materials, including fees paid to CMOs, and laboratory and vendor expenses related to the execution of our ongoing and planned preclinical studies and clinical trials.
Actual results could materially differ from those estimates. See Note 1 to the audited financial statements included in Item 8 - Financial Statements and Supplementary Data included elsewhere in this document for critical accounting estimates as of June 30, 2024.
Actual results could materially differ from those estimates. See Note 2 to the audited financial statements included in Item 8 - Financial Statements and Supplementary Data included elsewhere in this document for critical accounting policies as of June 30, 2025. 94
Liquidity and Capital Resources We have incurred significant operating losses and negative cash flows from operations since our inception, and we anticipate that we will incur net losses for the next several fiscal years. As of June 30, 2024, we had cash and cash equivalents of $12.6 million and an accumulated deficit of $178.0 million.
Liquidity and Capital Resources We have incurred significant operating losses and negative cash flows from operations since our inception, and we anticipate that we will incur net losses for the next several fiscal years. As of June 30, 2025, we had cash and cash equivalents of $14.2 million and an accumulated deficit of $178.3 million.
Our general and administration expenses consist primarily of: ● personnel costs, which include salaries, benefits and share-based compensation; ● expenses incurred under agreements with outside consultants and advisors, including their fees and related travel expenses; 113 ● filing and maintenance of patents and intellectual property rights; ● costs relating to audit, tax and regulatory compliance; and ● other expenses, including facilities costs, legal fees and insurance.
Our general and administration expenses consist primarily of : • personnel costs, which include salaries, benefits and share-based compensation; • expenses incurred under agreements with outside consultants and advisors, including their fees and related travel expenses; • costs relating to audit, tax, and regulatory compliance; and 90 • other expenses including facilities costs, legal fees, and insurance.
Sales of ADSs under the ATM Program may be made from time to time, with the timing and amount of any sales to be determined by Bionomics based on a variety of factors. Bionomics may determine to sell some, all, or none of the ADSs under the ATM Program and may terminate the ATM Program at its discretion.
Sales of the Shares under the Sales Agreement may be made from time to time, with the timing and amount of any sales to be determined by Neuphoria based on a variety of factors. Neuphoria may determine to sell some, all, or none of the Shares under the Sales agreement and may terminate the ATM facility at its discretion.
Components of Operating Results from Continuing Operations Expenses Our expenses since inception have consisted primarily of research and development expenses, general and administrative expenses, and other costs. 111 Research and Development Expenses Our research and development expenses represent costs incurred to conduct discovery and development of our proprietary drug candidates and consist primarily of: ● personnel costs, which include salaries, benefits and share-based compensation; ● expenses incurred under agreements with outside consultants and advisors, including their fees and related travel expenses; and ● expenses incurred under agreements with third parties, including CROs that conduct research, preclinical activities and clinical trials on our behalf as well as CMOs that manufacture our product candidates for use in our preclinical studies and clinical trials and perform other required manufacturing activities.
Research and Development Expenses Our research and development expenses represent costs incurred to conduct discovery and development of our proprietary drug candidates and consist primarily of: • personnel costs, which include salaries, benefits and share-based compensation; • expenses incurred under agreements with outside consultants and advisors, including their fees and related travel expenses; and • expenses incurred under agreements with third parties, including Contract Research Organizations ("CROs") that conduct research, preclinical activities, and clinical trials on our behalf, as well as Contract Manufacturing Organizations ("CMOs") that manufacture our product candidates for use in our preclinical studies and clinical trials and perform other required manufacturing activities.
The first tranche of the private placement closed in June 2024, resulting in aggregate gross proceeds to Bionomics of $7.5 million. For further information, see Item 5 – Recent Sales of Unregistered Securities. Funding Requirements Any product candidates we may develop may never achieve commercialization and we anticipate that we will continue to incur losses for the foreseeable future.
The first tranche of the private placement closed in June 2024, resulting in aggregate gross proceeds to the Company of $7.5 million. Funding Requirements Any product candidates we may develop may never achieve commercialization and we anticipate that we will continue to incur losses for the foreseeable future.
Since inception, we have had significant operating losses. Our net loss after tax was $15.5 million and $21.4 million for the years ended June 30, 2024 and 2023, respectively. As of June 30, 2024, we had an accumulated deficit of $178.0 million and cash and cash equivalents of $12.6 million.
Since inception, we have had significant operating losses. Our net loss after tax was $0.4 million and $15.5 million for the twelve months ended June 30, 2025 and 2024, respectively. As of June 30, 2025, we had an accumulated deficit of $178.3 million and cash and cash equivalents of $14.2 million.
Based upon the Company’s current operating plans, the Company believes that its existing cash and cash equivalents, combined with its existing ATM facility, will be sufficient to continue funding its development activities into late in the first quarter of fiscal year 2026, which is less than twelve months from the date these consolidated financial statements are issued.
Based upon the Company’s current operating plans, the Company believes that its existing cash and cash equivalents will be sufficient to continue funding its development activities through the second quarter of fiscal year 2027, which is more than twelve months from the date these consolidated financial statements are issued.
As of June 30, 2024, our operations have been financed primarily by aggregate net proceeds of $191.5 million from the sale and issuances of our equity, $13.5 million in the form of an upfront payment, research funding and a milestone payment from the 2014 MSD License Agreement, and $66.8 million from Australian research and development credits and government grants and assistance.
As of June 30, 2025, our operations have been financed primarily by aggregate net proceeds of $193.0 million from the sale and issuances of our equity, $29.2 million in the form of upfront payments, research funding, and a milestone payment from the 2014 Merck License Agreement, and $67.1 million from Australian research and development credits and government grants and assistance.
Our primary uses of capital are, and we expect will continue to be, compensation and related expenses (including share-based compensation); costs related to third-party clinical research, non-clinical research, manufacturing and development services; costs relating to the build-out of our headquarters and other offices; license payments or milestone obligations that may arise; legal and other regulatory expenses and general overhead costs. 116 Based upon our current operating plan, we believe that our existing cash and cash equivalents, combined with our existing ATM facility, will be sufficient to continue funding our development activities through late in the first quarter of fiscal year 2026.
Our primary uses of capital are, and we expect will continue to be, compensation and related expenses (including share-based compensation); costs related to third-party clinical research, non-clinical research, manufacturing and development services; costs relating to the build-out of our headquarters and other offices; license payments or milestone obligations that may arise; legal and other regulatory expenses and general overhead costs.
We currently intend to use the net proceeds from the ATM, together with its existing cash and cash equivalents, to fund our pipeline development, to maintain working capital and for general corporate purposes.
As a result, actual sales prices may vary. Neuphoria currently intends to use the net proceeds from the ATM, together with its existing cash and cash equivalents, to fund its pipeline development and to maintain working capital and for general corporate purposes.
Other Income The increase in other income of $1.9 million for fiscal year 2024, as compared to fiscal year 2023, was primarily due to increases in the fair value adjustment of our contingent consideration liability and our warrant liability of $2.8 million, partially offset by a decrease in interest income of $0.1 million, an increased loss in realized foreign currency transaction expense of $0.5 million, and a decrease in the research and development incentive award of $0.3 million.
Other Income The decrease in other income of $2.0 million other income for the fiscal year ended June 30, 2025, as compared to the fiscal year ended June 30, 2024, was primarily due to net changes in the fair value adjustment of our contingent consideration liability and our warrant liability of $2.0 million combined with an increase in the loss realized on foreign currency translation of $0.2 million, partially offset by an increase in the research and development incentive award of $0.2 million.
The following table sets forth the primary sources and uses of cash for each of the periods presented: Comparison of Fiscal Years ended June 30, 2024 and 2023 Fiscal Year ended June 30, 2024 2023 Net cash used in operating activities $ (14,680,777 ) $ (14,637,720 ) Net cash provided by financing activities 15,108,794 3,858,451 Net increase (decrease) in cash and cash equivalents $ 428,017 $ (10,779,269 ) 115 Operating Activities The less than $0.1 million decrease in net cash used in operating activities from $14.7 million for fiscal year 2023 to $14.6 million for fiscal year 2024 reflects a $5.9 million decrease in net loss combined with a favorable $0.5 million change in the effect of foreign currency translation and remeasurement in year 2024, as compared to fiscal year 2023, partially offset by a $0.5 million decrease in year-over year share-based compensation expense, a favorable $2.8 million year-over-year change in fair value adjustments on the warrant and contingent consideration liabilities, and a $3.1 million year-over-year change in working capital.
The following table sets forth the primary sources and uses of cash for each of the periods presented: Comparison of Fiscal Years ended June 30, 2025 and 2024 Year Ended June 30, 2025 2024 Net cash provided by (used in) operating activities $ 77,229 $ (14,680,777 ) Net cash provided by financing activities 1,528,276 15,108,794 Effect of exchange rate on changes on cash, cash equivalents, and restricted cash (3,750 ) 76,974 Net increase in cash, cash equivalents, and restricted cash $ 1,601,755 $ 504,991 Operating Activities The $14.8 million increase in net cash provided by operating activities to $0.1 million in the fiscal year ended June 30, 2025, from $14.7 million used in operating activities for fiscal year ended June 30, 2024, is primarily attributed to a $15.1 million decrease in net loss combined with a favorable $2.6 million change in the fair value adjustment associated with the contingent consideration liability and a favorable $0.3 million effect of foreign currency translation in the year ended June 30, 2025, as compared to the same period in 2024, partially offset by an unfavorable $0.7 million change in year-over year share-based compensation expense, an unfavorable $0.6 million year-over-year change in fair value adjustments associated with the warrant liability, and an unfavorable $1.9 million year-over-year change in working capital.
Of the total BNC210-based program spend during the year ended June 30, 2024, approximately 35% was attributable to PSTD ATTUNE, 40% to SAD Prevail, and 25% to overall CMC costs. We do not track labor associated with each program and have allocated headcount costs on a pro-rated basis.
In the fiscal year ended June 30, 2025, approximately 88% of the total 2025 research and development expenses related to the advancement of our BNC210-based programs. Of the 88%, approximately 13% were attributable to PSTD ATTUNE and 75% to SAD Prevail. We do not track labor associated with each program and have allocated headcount costs on a pro rata basis.
Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical trials and our expenditure on other research and development activities. 110 In accordance with ASC 205-40, Going Concern , the Company has evaluated whether there are conditions and events, considered in the aggregate, that raise substantial doubt about the Company’s ability to continue as a going concern within one year after the date the financial statements included in this Annual Report on Form 10-K are issued.
In accordance with ASC 205-40, Going Concern , the Company has evaluated whether there are conditions and events, considered in the aggregate, that raise substantial doubt about the Company’s ability to continue as a going concern within one year after the date these consolidated financial statements are issued.
We have a long-term operating lease obligation for our Australian office space and a non-current warrant liability which commits us to issuing shares to accompanying warrant holders upon the exercise of their ADS warrants. 117 Critical Accounting Estimates The preparation of audited financial statements and related disclosures in conformity with accounting principles generally accepted in the United States of America requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent assets and liabilities at the date of the audited financial statements, and income and expenses during the periods reported.
Critical Accounting Policies The preparation of audited financial statements and related disclosures in conformity with accounting principles generally accepted in the United States of America requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent assets and liabilities at the date of the audited financial statements, and income and expenses during the periods reported.
Bionomics, through Cantor, may sell ADSs by any lawful method deemed to be an “at-the-market offering”. Sales made through the ATM Program may be made at market prices prevailing at the time of a sale or at prices related to prevailing market prices. As a result, actual sales prices may vary.
Neuphoria, through the Sales Agent, may sell Shares by any lawful method deemed to be an “at-the-market offering” defined by Rule 415(a)(4) under the Securities Act of 1933, as amended. Sales made through the Sales Agreement may be made at market prices prevailing at the time of a sale or at prices related to prevailing market prices.
In addition, if we seek and obtain regulatory approval to commercialize any product candidate, we will also incur increased expenses in connection with commercialization and marketing of any such product.
In addition, if we seek and obtain regulatory approval to commercialize any product candidate, we will also incur increased expenses in connection with commercialization and marketing of any such product. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical trials and our expenditure on other research and development activities.
During fiscal year ended June 30, 2024, we issued an aggregate of 3,791,317 ADSs under the ATM program, receiving gross proceeds in the aggregate amount of approximately $8.9 million.
During the fiscal year ended June 30, 2025, we issued an aggregate of 349,801 shares of common stock under the ATM facility, receiving gross proceeds in the aggregate amount of approximately $2.1 million.
Investing Activities There were no transactions categorized as investing activities during either of fiscal years 2024 or 2023. Financing Activities Financing activities in the fiscal year ended June 30, 2024 included gross proceeds of $16.4 million from the sale and issuance of ADSs and warrants, partially offset by equity issuance costs of $1.3 million.
Financing activities in the fiscal year ended June 30, 2025 included gross proceeds of $1.9 million from the sale and issuance of shares partially offset by equity issuance costs of $0.1 million.
Pursuant to the 2014 MSD License Agreement, we received upfront payments totaling A$20 million, and another A$10 million in February 2017 when the first compound from the collaboration entered Phase 1 clinical trials and we are eligible to receive up to an additional A$465 million in milestone payments for achievement of certain development and commercial milestones.
Pursuant to the Merck Agreement, we received upfront payments totaling $17 million, another $10 million in February 2017 when the first compound from the collaboration entered Phase 1 clinical trials, and another $15 million in March 2025 upon the first dosing of a patient in a Phase 2 clinical trial.
The decrease in the fiscal year ended June 30, 2024 of approximately $3.6 million as compared to the fiscal year ended June 30, 2023 was primarily due to decreased expenditures associated with the PTSD ATTUNE clinical trial, which started during July 2021, the SAD PREVAIL clinical trial, which started during February 2022, and work in relation to preparation for an End-of-Phase 2 meeting with the FDA to discuss our Phase 3 clinical program in SAD. 114 In the fiscal year ended June 30, 2024, approximately 85% of the total research and development expenses related to the advancement of our BNC210-based programs.
The decrease in the fiscal year ended June 30, 2025 of approximately $0.4 million as compared to the fiscal year ended June 30, 2024 was primarily due to decreased expenditures associated with the PTSD ATTUNE program of $3.0 million combined with decreased expenditures for consulting costs of $0.1 million and professional services of $0.1 million, partially offset by increases in costs associated with the SAD PREVAIL program of $2.3 million, combined with an increase in other program spend of $0.1 million and increases in headcount and other costs of $0.2 million.
Accordingly, based on its recurring losses from operations incurred since inception, the expectation of continued operating losses, and the need to raise additional capital to finance its future operations, the Company determined that there is substantial doubt about the Company’s ability to continue as a going concern within twelve months of the issuance date of these financial statements.
Consequently, management has determined there is no substantial doubt regarding the Company's ability to continue as a going concern for the twelve month period from the date these financial statements are issued. The Company has projected its operating capital requirements based on its current operating plan, which management believes can be effectively implemented.
General and Administrative Expenses The decrease in general and administrative expenses in fiscal year 2024 of $0.4 million as compared to fiscal year 2023 was due to decreases in headcount-related costs of $1.0 million resulting from costs associated with hiring a new Chief Executive Officer and paying out severance to the outgoing CEO in fiscal year 2023, and decreased insurance expense in the current year of $0.8 million, partially offset by increases in administrative costs associated with our delisting from the ASX of $0.3 million, increased public relations costs in support of fundraising efforts of $0.4 million, and warrant liability issuance costs of $0.7 million associated with the private placement that closed in June 2024 and which is further discussed below in “ Financing Activities” .
General and Administrative Expenses The decrease in general and administrative expenses in the fiscal year ended June 30, 2025 of $0.7 million as compared to the fiscal year ended June 30, 2024 was due to decreases in headcount-related costs of $0.3 million due to normal fluctuations in staffing levels 91 during the fiscal year ended June 30, 2025 and decreased insurance expense in the current year of $0.5 million, partially offset by increases in administrative costs of $0.2 million.
Financing activities in fiscal year 2023 included $5.0 million of gross proceeds from the sale and issuance of ADSs, partially offset by equity issuance costs of $1.1 million. In May 2023, the Company announced the establishment of an “at-the-market” program (the “ATM Program”) with Cantor Fitzgerald & Co. (“Cantor”) as sales agent.
Financing activities in the fiscal year ended 92 June 30, 2024 included $16.4 million of gross proceeds from the sale and issuance of shares and warrant, partially offset by equity issuance costs of $0.4 million. On November 18, 2024, the Company entered into an At The Market Offering Agreement (the “Sales Agreement”) with H.C.
Results of Operations Comparison of Fiscal Years ended June 30, 2024 and 2023 Fiscal Year ended June 30, Increase (Decrease) 2024 2023 Amount Percent Research and development expenses $ (9,417,785 ) $ (13,071,705 ) $ (3,653,920 ) (28.0 )% General and administrative expenses (8,474,591 ) (8,911,271 ) $ (436,680 ) (4.9 )% Other income 2,312,890 462,125 $ 1,850,764 400.5 % Loss before income taxes $ (15,579,486 ) $ (21,520,851 ) Research and Development Expenses Our research and development activities in the fiscal years ended June 30, 2024 and June 30, 2023 were principally focused on the advancement of BNC210.
Results of Operations Comparison of Fiscal Years ended June 30, 2025 and 2024 Year Ended June 30, Increase (Decrease) 2025 2024 Amount Percent License revenue $ 15,649,448 $ - $ 15,649,448 N/A Research and development (9,005,097 ) (9,417,785 ) (412,688 ) (4.4 )% General and administrative (7,773,442 ) (8,474,591 ) (701,149 ) (8.3 )% Other income 291,093 2,312,890 (2,021,797 ) 87.4 % Loss before income tax expense $ (837,998 ) $ (15,579,486 ) License Revenue Our license revenue increased during the twelve months ended June 30, 2025, as compared to the same period ended 2024, primarily due to the $15 million milestone payment received from the Merck Agreement in March 2025.
Removed
The Company incurred net losses of $15.5 million and $21.4 million for the years ended June 30, 2024 and 2023, respectively. The Company also used $14.6 million of cash for operating activities during each of the years ended June 30, 2024 and 2023.
Added
The Company incurred a net loss of $0.4 million for the twelve months ended June 30, 2025 inclusive of the receipt of milestone payments associated with our research collaboration and licensing agreements and 87 incurred a net loss of $15.5 million for the twelve months ended June 30, 2024.
Removed
Further, MSD is obligated to pay us tiered royalties in the mid-single digit to low sub-teen double digit percentage range on net sales of the licensed products, subject to reduction upon certain events. In November 2020, we entered into an IP license agreement (the “Carina Biotech License”) with Carina Biotech.
Added
The Company also generated $0.1 of cash for operating activities during the twelve months ended June 30, 2025.
Removed
To date, no payments have been made pursuant to the Carina Biotech License.
Added
The operating plan incorporates several assumptions that, while considered probable, may ultimately prove to be incorrect, and the Company may use all available capital resources sooner than expected.
Removed
Under the ATM Program, the Company may offer and sell up to $11.5 million of ordinary shares in the form of ADSs, with each ADS representing 180 fully paid ordinary shares, through Cantor.
Added
The accompanying consolidated financial statements do not include adjustments that might result from the outcome of uncertainties and assumes the Company will continue as a going concern through the realization of assets and satisfaction of liabilities and commitments in the ordinary course of business.
Removed
We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. To finance our operations beyond that point we will need to raise additional capital, which cannot be assured.
Added
Although the Company has been successful in raising capital in the past, there is no assurance that it will be successful in obtaining such additional financing on terms acceptable to the Company, if at all, nor is it considered probable under the accounting standards.
Added
If the Company is unable to obtain sufficient funding on acceptable terms, it could be forced to delay, reduce, or eliminate some or all its research and development programs or commercialization activities, which could materially adversely affect its business prospects or its ability to continue operations.
Added
We are also eligible to receive up to an additional $450 million in milestone payments for achievement of certain development and commercial milestones.
Added
On March 14, 2025, the Company and Merck executed the Fifth Amendment to the Research Collaboration and License Agreement which amended the patent royalty rate set out in the Merck Agreement, such that, conditioned upon achievement of net sales thresholds set forth in the Merck Agreement, as amended, the Company will be paid royalties on net sales ranging from a low single digits percentage to a low sub-teens percentage, depending on net sales volume.
Added
There were no other changes in the transaction price during the twelve months ended June 30, 2025. In November 2020, we entered into an IP license agreement (the “Carina Biotech License”) with Carina Biotech ("Carina").
Added
On October 30, 2024, Carina made a milestone payment to the Company in the gross amount of A$1,000,000 which was recorded as revenue in the Consolidated Statement of Operations and Other Comprehensive Income (Loss) included in this Form 10-K. 88 Components of Operating Results from Continuing Operations License Revenue Our license revenue reflects revenue earned from customers attributed to our license agreements and the milestone payments earned thereunder.
Added
Expenses Our expenses since inception have consisted primarily of research and development expenses, general and administrative expenses, and other costs.
Added
Research and Development Expenses Our research and development activities during the twelve months ended June 30, 2025 and 2024, were principally focused on the advancement of BNC210.
Added
JOBS Act We are an emerging growth company, as defined in the JOBS Act. We rely on certain reduced reporting and other requirements that are otherwise generally applicable to public companies.
Added
As an emerging growth company, we are not required to, among other things, (i) provide an auditor’s attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act, which would otherwise be required beginning with our second annual report on Form 10-K, and (ii) comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements (auditor discussion and analysis).
Added
Financing Activities The $13.6 million decrease in net cash provided by financing activities to $1.5 million in the fiscal year ended June 30, 2025, from $15.1 million provided by financing activities for fiscal year ended June 30, 2024, is primarily due a decrease in proceeds from the sale of our equity instruments.
Added
Wainwright & Co., LLC (the “Sales Agent”). Pursuant to the Sales Agreement, the Sales Agent will act as the Company’s agent with respect to an offering and sale, at any time and from time to time, of the Company’s shares of common stock (the “Shares”) in an aggregate offering amount up to $11,494,900 under the Sales Agreement.
Added
The current ATM program replaces previous ATM program dated May 5, 2023, between the Company and Cantor Fitzgerald & Co., which was terminated by the Company in order to proceed with the new ATM offering with the Sales Agent.
Added
Based upon our current operating plan, we believe that our existing cash and cash equivalents, combined with anticipated financing transactions, will be sufficient to continue funding our development activities through the second quarter of fiscal year 2027. To finance our operations beyond that point we will need to raise additional capital, which cannot be assured.
Added
Because of the numerous risks and uncertainties associated with research, development and commercialization of pharmaceutical products, we are unable to estimate the exact amount of our operating capital requirements.
Added
Our future capital requirements depend on many factors, including but not limited to: • the scope, progress, results and costs of independently researching and developing any of our product candidates and conducting preclinical studies and clinical trials; 93 • the timing, receipt and amount of milestone payments, if any, from Merck under the 2014 Merck License Agreement to develop and commercialize compounds targeting cognitive dysfunction associated with Alzheimer’s disease and other central nervous system conditions; • the timing and receipt of proceeds on the exercise of the warrant and share options, if at all exercised; • the number, indications and characteristics of the product candidates we pursue; • the cost of manufacturing our approved drugs, if any; • the cost of commercialization activities; • our ability to maintain existing collaborations and to establish new collaborations, licensing or other arrangements and the financial terms of such agreements; and • the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing patents, including litigation costs and the outcome of such litigation.
Added
We do have a long-term operating lease obligation for our Australian facility and a non-current warrant liability which commits us to issuing shares to a warrant holders upon the exercise of their common stock warrant.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

7 edited+2 added−1 removed2 unchanged
Quantitative and Qualitative Disclosures About Market Risk Foreign Currency Risk The following table summarizes our exposure to foreign currency risk (all of which are risks against the Australian dollar), expressed in U.S. dollars as of June 30, 2024 and 2023: June 30, 2024 2023 (in thousands) Monetary items Cash and cash equivalents $ 5,533 $ 15,699 Restricted cash 119 119 Accounts receivable, non-trade 192 643 Accounts payable (245 ) (461 ) Accrued expenses and other current liabilities (1,501 ) (1,025 ) Operating lease liability (362 ) (534 ) Total Monetary Items $ 3,736 $ 14,441 Non-monetary items Prepaid expenses $ 691 $ 1,202 Operating lease right-of-use assets, net 328 498 Intangible assets, net (goodwill) 6,947 6,947 Total Non-Monetary Items $ 7,966 $ 8,647 Total Monetary and Non-Monetary Items $ 11,702 $ 23,088 The following table sets forth a sensitivity analysis of our exposure to a 10% increase and decrease in the Australian dollar against the U.S. dollar.
Foreign Currency Risk The following table summarizes our exposure to foreign currency risk (all of which are risks against the Australian dollar), expressed in U.S. dollars as of June 30, 2025 and 2024: June 30, 2025 2024 (in thousands) Monetary items Cash and cash equivalents $ 132 $ 5,533 Restricted cash 78 119 Accounts receivable, non-trade 12 192 Accounts payable (700 ) (245 ) Accrued expenses and other current liabilities (2,304 ) (1,501 ) Operating lease liability (116 ) (362 ) Total Monetary Items $ (2,898 ) $ 3,736 Non-monetary items Prepaid expenses $ 169 $ 691 Operating lease right-of-use assets, net — 328 Intangible assets, net (goodwill) 4,550.0 6,947.0 Total Non-Monetary Items $ 4,719 $ 7,966 Total Monetary and Non-Monetary Items $ 1,821 $ 11,702 The following table sets forth a sensitivity analysis of our exposure to a 10% increase and decrease in the Australian dollar against the U.S. dollar.
Due to the size of potential milestone payments under our license and collaboration agreement with MSD, in fiscal years when we record receivables under this agreement, MSD is likely to represent a large percentage of our trade and other receivable balance and our revenue in such fiscal years.
Due to the size of potential milestone payments under our license and collaboration agreement with Merck, in fiscal years when we record receivables under this agreement, Merck is likely to represent a large percentage of our trade and other receivable balance and our revenue in such fiscal years. 95 Liquidity Risk Ultimate responsibility for liquidity risk management rests with our board of directors, which has approved a liquidity risk management framework for management of our short, medium and long-term funding.
We have adopted a policy of only dealing with creditworthy counterparties and obtaining sufficient collateral, where appropriate, as a means of mitigating the risk of financial loss from defaults. We consider all of our material counterparties to be creditworthy.
Credit Risk Credit risk refers to the risk that a counterparty will default on its contractual obligations resulting in a financial loss to us. We have adopted a policy of only dealing with creditworthy counterparties and obtaining sufficient collateral, where appropriate, as a means of mitigating the risk of financial loss from defaults.
Our sensitivity to foreign currency has decreased as of June 30, 2024 due primarily to a decrease in cash and cash equivalents that are denominated in Australian dollars, which is a direct result of U.S. fundraising activities and the continued maintenance of U.S.-based clinical research activities. 118 Credit Risk Credit risk refers to the risk that a counterparty will default on its contractual obligations resulting in a financial loss to us.
Our sensitivity to foreign currency has decreased as of June 30, 2025 due primarily to a decrease in cash and cash equivalents that are denominated in Australian dollars which is a direct result of U.S. fundraising activities and the receipt of milestone revenue denominated in USD.
June 30, 2024 2023 10% increase Profit or loss (i) $ 652,388 $ 2,210,510 Equity (ii) $ 953,433 $ 952,570 10% decrease Profit or loss (i) $ (652,388 ) $ (2,210,550 ) Equity (ii) $ (953,433 ) $ (952,570 ) (i) This is attributable to the exposure to outstanding USD net monetary assets at the end of the reporting period.
June 30, 2025 2024 10% increase (i) Profit or loss $ 1,269,444 $ 652,388 Equity $ 1,747,371 $ 953,433 10% decrease (i) Profit or loss $ (1,714,974 ) $ (652,388 ) Equity $ (1,747,371 ) $ (953,433 ) (i) This is attributable to the exposure to outstanding A$ net monetary assets at the end of the reporting period in the subsidiary which is denominated in USD and reflected in the foreign currency translation reserve.
Inflation We do not believe that inflation has had a material effect on our business, financial condition, or results of operations. If our costs become subject to significant inflationary pressures, this could harm our business, financial condition, and operating results.
If our costs become subject to significant inflationary pressures, this could harm our business, financial condition, and operating results. 96
Liquidity Risk Ultimate responsibility for liquidity risk management rests with our board of directors, which has approved a liquidity risk management framework for management of our short-, medium- and long-term funding. We manage liquidity risk by continuously monitoring forecast and actual cash flows and matching maturity profiles of financial assets and liabilities.
We manage liquidity risk by continuously monitoring forecast, actual cash flows, and matching maturity profiles of financial assets and liabilities. Inflation We do not believe that inflation has had a material effect on our business, financial condition, or results of operations during the twelve months ended June 30, 2025.
Removed
(ii) This is attributable to the exposure to outstanding USD net monetary assets at the end of the reporting period in the subsidiaries which is denominated in USD and reflected in the foreign currency translation reserve.
Added
Item 7A. Quantitative and Qualitative Disclosures About Market Risk.
Added
We consider all of our material counterparties to be creditworthy.

Other NEUP 10-K year-over-year comparisons