10q10k10q10k.net

What changed in ARS Pharmaceuticals, Inc.'s 10-K — 2022 vs 2023

vs

Paragraph-level year-over-year comparison of ARS Pharmaceuticals, Inc.'s 2022 and 2023 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2023 report.

+496 added−463 removedSource: 10-K (2024-03-21) vs 10-K (2023-03-23)

Top changes in ARS Pharmaceuticals, Inc.'s 2023 10-K

496 paragraphs added · 463 removed · 370 edited across 5 sections

Item 1. Business

Business — how the company describes what it does

145 edited+48 added−28 removed327 unchanged
Biggest changeSuch obligations may include, without limitation, HIPAA, the Federal Trade Commission Act, the California Consumer Privacy Act of 2018 (“CCPA”), the Canadian Personal Information Protection and Electronic Documents Act, Canada’s Anti-Spam Legislation, the European Union’s General Data Protection Regulation 2016/679 (“EU GDPR”), and the EU GDPR as it forms part of United Kingdom (“UK”) law by virtue of section 3 of the European Union (Withdrawal) Act 2018 (“UK GDPR”).HIPAA, as amended by HITECH, imposes obligations, including mandatory contractual terms, on certain covered healthcare providers, health plans, and healthcare clearinghouses and their respective business associates and covered subcontractors that perform services for them that involve the use, or disclosure of, individually identifiable health information with respect to safeguarding the privacy, security and transmission of individually identifiable health information.
Biggest changeSuch obligations may include, without limitation, HIPAA, the Federal Trade Commission Act, the California Consumer Privacy Act of 2018 (“CCPA”), the Canadian Personal Information Protection and Electronic Documents Act, Canada’s Anti-Spam Legislation, the EU’s General Data Protection Regulation 2016/679 (“EU GDPR”), and the EU GDPR as it forms part of United Kingdom (“UK”) law by virtue of section 3 of the EU (Withdrawal) Act 2018 (“UK GDPR”).
Shah, our Chairman, has more than 30 years of experience founding and leading biopharmaceutical companies and healthcare investment decisions including his role as Executive Chairman of Design Therapeutics, former Chairman of Synthorx (now part of Sanofi) and former Chief Executive Officer of Auspex Pharmaceuticals (now part of Teva Pharmaceuticals).
Shah, our Chairman, has more than 30 years of experience founding and leading biopharmaceutical companies and healthcare investment decisions including his role as Chairman and Chief Executive Officer of Design Therapeutics, former Chairman of Synthorx (now part of Sanofi) and former Chief Executive Officer of Auspex Pharmaceuticals (now part of Teva Pharmaceuticals).
The FDA reference listed drug is intra-muscular needle-in-syringe injection products but there are several approved epinephrine intra-muscular injection products, including intra-muscular auto-injectors such as EpiPen, that establish a range of exposures that have indistinguishable efficacy, time to observed clinical effect and safety.
The FDA reference listed drug is intra-muscular needle-in-syringe injection products but there are several approved epinephrine injection products, including auto-injectors such as EpiPen, that establish a range of exposures that have indistinguishable efficacy, time to observed clinical effect and safety.
The agreement contains conventional commercial pharmaceutical manufacturing provisions including certain minimum purchase amounts to be determined in the future based on forecast needs and minimum batch size projections. We may also request Renaissance perform certain services related to the Renaissance Product, for which we will pay reasonable compensation to Renaissance.
The agreement contains conventional commercial pharmaceutical manufacturing provisions including certain minimum purchase amounts to be determined in the future based on forecast needs and minimum batch size projections. We may also request Renaissance to perform certain services related to the Renaissance Product, for which we will pay reasonable compensation to Renaissance.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions and typically follows the advisory committee’s recommendations. Before approving an NDA, the FDA will inspect the facilities at which the product is manufactured.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions and typically follows such committee’s recommendations. Before approving an NDA, the FDA will inspect the facilities at which the product is manufactured.
Corporate Information Our corporate headquarters are located at 11682 El Camino Real, Suite 120, San Diego, California 92130, and our telephone number is (858) 771-9307. Our corporate website address is www.ars-pharma.com. Information contained on, or accessible through, our website shall not be deemed incorporated into and is not a part of this Annual Report on Form 10-K.
Our corporate headquarters are located at 11682 El Camino Real, Suite 120, San Diego, California 92130, and our telephone number is (858) 771-9307. Our corporate website address is www.ars-pharma.com. Information contained on, or accessible through, our website shall not be deemed incorporated into and is not a part of this Annual Report on Form 10-K.
These two earlier-stage studies were conducted in the United States on behalf of ARS Pharma by WCCT Global, Inc. and Altasciences Clinical Los Angeles, Inc, respectively, and selected a total of 26 healthy male or female volunteers between the ages of 18 to 55 years, and 42 male or female volunteers between the ages of 18 to 55 years who had an ongoing history of type I allergies. 15 2.0 mg neffy is intended to be the dose that is comparable to approved 0.3 mg epinephrine intra-muscular injection products for persons greater than 30 kg in weight, which represents approximately 80% of the prescriptions in the United States. 1.0 mg neffy is intended to be the dose for persons 15 to 30 kg in weight.
These two earlier-stage studies were conducted in the United States on behalf of ARS Pharma by WCCT Global, Inc. and Altasciences Clinical Los Angeles, Inc, respectively, and selected a total of 26 healthy male or female volunteers between the ages of 18 to 55 years, and 42 male or female volunteers between the ages of 18 to 55 years who had an ongoing history of type I allergies. 17 2.0 mg neffy is intended to be the dose that is comparable to approved 0.3 mg epinephrine intra-muscular injection products for persons greater than 30 kg in weight, which represents approximately 80% of the prescriptions in the United States. 1.0 mg neffy is intended to be the dose for persons 15 to 30 kg in weight.
Robust PDs within a range comparable to injection products with no risk of accidental blood vessel injections PD responses including systolic blood pressure and heart rate were within normal physiologic changes and comparable to auto-injector products, with maximum changes less that of the EpiPen. neffy has no potential for the accidental blood vessel injections observed with injection products such as EpiPen, which can lead to rapid and high epinephrine exposures that cause rapid increases in systolic blood pressure and can lead to cerebral hemorrhage or other cardiovascular side effects.
Robust PDs within a range comparable to injection products with no risk of accidental blood vessel injections PD responses including systolic blood pressure and heart rate were within normal physiologic changes and comparable to auto-injector products, with maximum changes less than EpiPen. neffy has no potential for the accidental blood vessel injections observed with injection products such as EpiPen, which can lead to rapid and high epinephrine exposures that cause rapid increases in systolic blood pressure and can lead to cerebral hemorrhage or other cardiovascular side effects.
We plan to initially commercialize neffy in the United States with a combination of direct promotion, virtual sales consultants, and non-personal promotion intended to reach, at a minimum, the healthcare professionals that account for 45% of the current epinephrine prescriptions. Our promotion will focus the launch on the highest potential practicing allergists, pediatricians, and primary care physicians.
We plan to initially commercialize neffy in the United States with a combination of direct promotion, virtual sales consultants, and non-personal promotion intended to reach, at a minimum, the healthcare professionals that account for 40 to 45% of the current epinephrine prescriptions. Our promotion will focus the launch on the highest potential practicing allergists, pediatricians, and primary care physicians.
Delay in treatment can allow the allergic reaction to progress in severity leading to symptoms that seriously impact patient quality of life, to potential need for emergency services and/or hospitalizations, and to life-threatening symptoms or events. There are approximately 25 to 40 million people in the United States who experience Type I allergic reactions.
Delay in treatment can allow the allergic reaction to progress in severity leading to symptoms that seriously impact patient quality of life, to potential need for emergency services and/or hospitalizations, and to life-threatening symptoms or events. There are approximately 40 million people in the United States who experience Type I allergic reactions.
We intend to continue to protect all personal information in our control and to comply with all applicable laws regarding the protection of such information. 37 The CCPA and EU GDPR are examples of the increasingly stringent and evolving regulatory frameworks related to personal data processing that may increase our compliance obligations and exposure for any noncompliance.
We intend to continue to protect all personal information in our control and to comply with all applicable laws regarding the protection of such information. The CCPA and EU GDPR are examples of the increasingly stringent and evolving regulatory frameworks related to personal data processing that may increase our compliance obligations and exposure for any noncompliance.
If neffy is approved by the FDA, we plan to initially commercialize it in the United States by deploying a combination of direct promotion, virtual sales consultants, and non-personal promotion intended to reach, at a minimum, the healthcare professionals that account for 45% of the current epinephrine prescriptions.
If neffy is approved by the FDA, we plan to initially commercialize it in the United States by deploying a combination of direct promotion, virtual sales consultants, and non-personal promotion intended to reach, at a minimum, the healthcare professionals that account for 40 to 45% of the current epinephrine prescriptions.
Either party may terminate the agreement for uncured material breach of the other party, or upon notice for insolvency-related events of the other party that are not discharged within a defined time period. 25 Collaboration and License Agreement with Alfresa In April 2020, we entered into a collaboration and license agreement with Alfresa Pharma Corporation (“Alfresa”).
Either party may terminate the agreement for uncured material breach of the other party, or upon notice for insolvency-related events of the other party that are not discharged within a defined time period. Collaboration and License Agreement with Alfresa In April 2020, we entered into a collaboration and license agreement with Alfresa Pharma Corporation (“Alfresa”).
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, preclinical animal studies and formulation studies in accordance with applicable regulations, including the FDA’s Good Laboratory Practice (“GLP”) regulations and other applicable regulations; • submission to the FDA of an investigational new drug (“IND”), which must become effective before human clinical trials may begin; • approval by an independent institutional review board (“IRB”) at each clinical site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with applicable regulations, including the FDA’s good clinical practice (“GCP”) regulations to establish the safety and efficacy of the proposed drug for its proposed indication; • 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 file the NDA for review; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug is 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 preclinical and/or clinical trial sites that generated the data in support of the NDA to assess compliance with GCP regulations; • satisfactory completion of an FDA advisory committee review, if applicable; and • FDA review and approval of the NDA prior to any commercial marketing or sale of the drug in the United States.
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, preclinical animal studies and formulation studies in accordance with applicable regulations, including the FDA’s Good Laboratory Practice (“GLP”) regulations and other applicable regulations; • submission to the FDA of an investigational new drug (“IND”), which must become effective before human clinical trials may begin; • approval by an independent institutional review board (“IRB”) at each clinical site before each trial may be initiated; • performance of adequate and well-controlled human clinical trials in accordance with applicable regulations, including the FDA’s good clinical practice (“GCP”) regulations to establish the safety and efficacy of the proposed drug for its proposed indication; • 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 file the NDA for review; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug is 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 preclinical and/or clinical trial sites that generated the data in support of the NDA to assess compliance with GCP regulations; • satisfactory completion of an FDA PADAC review, if applicable; and • FDA review and approval of the NDA prior to any commercial marketing or sale of the drug in the United States.
Either party may terminate the agreement for uncured material breach of the other party, or upon notice for insolvency-related events of the other party that are not discharged within a defined time period. Collaboration and Distribution Agreement with Pediatrix In March 2021, we entered into a collaboration and distribution agreement with Pediatrix Therapeutics (“Pediatrix”).
Either party may terminate the agreement for uncured material breach of the other party, or upon notice for insolvency-related events of the other party that are not discharged within a defined time period. 31 Collaboration and Distribution Agreement with Pediatrix In March 2021, we entered into a collaboration and distribution agreement with Pediatrix Therapeutics (“Pediatrix”).
These limitations include: • lack ease of portability with only 50% of patients filling prescriptions carrying the device; • reluctance to use the device with approximately 25% to 50% of patients carrying the device refusing to administer; • apprehension stemming from the use of a needle that leads to approximately 40% to 60% of patients delaying administration by up to 18 minutes even if they are carrying the device; • a high rate of dosing errors, with meta-analyses reporting up to 35% of patients still failing to dose correctly even after training; and • safety concerns including lacerations, caregiver self-injection and frequent potentially cardiotoxic blood vessel injections, which occurred in approximately 14% of EpiPen subjects in our patient self-administration studies.
These limitations include: • lack ease of portability with only 50% of patients filling prescriptions carrying the device; • reluctance to use the device with approximately 25% to 60% of patients carrying the device refusing to administer; • apprehension stemming from the use of a needle that leads to approximately 40% to 60% of patients delaying administration by up to 18 minutes even if they are carrying the device; • a high rate of dosing errors, with meta-analyses reporting 23% of patients still failing to dose correctly even after training; and • safety concerns including lacerations, caregiver self-injection and frequent potentially cardiotoxic blood vessel injections, which occurred in approximately 14% of EpiPen subjects in our patient self-administration studies.
The centralized procedure is optional for other products that represent a significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public health or which contain a new active substance for indications other than those specified to be compulsory. 38 National Authorization Procedures .
The centralized procedure is optional for other products that represent a significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public health or which contain a new active substance for indications other than those specified to be compulsory. National Authorization Procedures .
For more information, see “ Risk Factors—Risks Related to Our Intellectual Property. ” Our Collaboration and Licensing Agreements License Agreement with Aegis In June 2018, we entered into a license agreement with Aegis Therapeutics, LLC (“Aegis”), which was amended in July 2020 and January 2021.
For more information, see “ Risk Factors—Risks Related to Our Intellectual Property. ” 30 Our Collaboration and Licensing Agreements License Agreement with Aegis In June 2018, we entered into a license agreement with Aegis Therapeutics, LLC (“Aegis”), which was amended in July 2020 and January 2021.
Of 3.3 million patients that do fill their prescriptions, approximately half do not carry the intra-muscular injectable products with them on a regular basis, while many of the other half delay or hesitate treatment during a severe Type I allergic reaction.
Of 3.2 million patients that do fill their prescriptions, approximately half do not carry the intra-muscular injectable products with them on a regular basis, while many of the other half delay or hesitate treatment during a severe Type I allergic reaction.
We believe the advantages of neffy will be attractive to this group and lead to an increase in the number of patients filling their prescription as further described below. These patients are additive to the 3.3 million patients that do fill a prescription per year.
We believe the advantages of neffy will be attractive to this group and lead to an increase in the number of patients filling their prescription as further described below. These patients are additive to the 3.2 million patients that do fill a prescription per year.
Moreover, as a condition of participating in, and having products covered under, certain federal healthcare programs, such as Medicare and Medicaid, we are subject to federal laws and regulations that require pharmaceutical manufacturers to calculate and report certain price reporting metrics to the government, such as Medicaid Average Manufacturer Price (“AMP”), and Best Price, Medicare Average Sales Price, the 340B Ceiling Price, and Non-Federal AMP reported to the Department of Veteran Affairs, and with respect to Medicaid, pay statutory rebates on utilization of manufacturers’ products by Medicaid beneficiaries. 35 In international markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.
Moreover, as a condition of participating in, and having products covered under, certain federal healthcare programs, such as Medicare and Medicaid, we are subject to federal laws and regulations that require pharmaceutical manufacturers to calculate and report certain price reporting metrics to the government, such as Medicaid Average Manufacturer Price (“AMP”), and Best Price, Medicare Average Sales Price, the 340B Ceiling Price, and Non-Federal AMP reported to the Department of Veteran Affairs, and with respect to Medicaid, pay statutory rebates on utilization of manufacturers’ products by Medicaid beneficiaries. 41 In international markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.
Further, we will offer comprehensive patient support programs in the form of co-pay buydowns to help ensure access and affordability for all patients. We intend to expand the market beyond the 3.3 million patients currently filling epinephrine injection device prescriptions.
Further, we will offer comprehensive patient support programs in the form of co-pay buydowns to help ensure access and affordability for all patients. We intend to expand the market beyond the 3.2 million patients currently filling epinephrine injection device prescriptions.
We expect significant reach to be achieved based on expanded use of non-personal promotional tactics and virtual sales representatives to reach healthcare professionals and focus on the sequential activation of patient demand through direct-to-consumer tactics that will help also drive physician awareness due to overlapping exposure. 21 We intend to partner with patient advocacy organizations as well as influencers and leverage an omnichannel strategy including direct-to-patient and parent tactics, social and traditional media, digital presence, and additional public relations to drive awareness, for patients to ask for neffy , and communicate our value proposition .
We expect significant reach to be achieved based on expanded use of non-personal promotional tactics and virtual sales representatives to reach healthcare professionals and focus on the sequential activation of patient demand through direct-to-consumer tactics that will help also drive physician awareness due to overlapping exposure. 27 We intend to partner with patient advocacy organizations as well as influencers and leverage an omnichannel strategy including direct-to-patient and parent tactics, social and traditional media, digital presence, and additional public relations to drive awareness, for patients to ask for neffy , and communicate our value proposition .
Of those 3.3 million people, roughly half don’t carry these devices due to many drawbacks that can result in patient and caregiver injury, hesitation, and delays in administration principally because of apprehension and pain of needles.
Of those 3.2 million people, roughly half don’t carry these devices due to many drawbacks that can result in patient and caregiver injury, hesitation, and delays in administration principally because of apprehension and pain of needles.
The FDA may also impose clinical holds on a product candidate at any time before or during clinical trials due to safety concerns or non-compliance. 28 Clinical trials involve the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial.
The FDA may also impose clinical holds on a product candidate at any time before or during clinical trials due to safety concerns or non-compliance. 34 Clinical trials involve the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial.
Currently, we estimate only between 20% to 30% of patients currently obtain more than one pack (containing two devices) per year today. 19 US Market Expansion Opportunity While we believe the existing epinephrine intra-muscular injectables market is a large commercial opportunity for neffy with multiple independent opportunities for further growth, IQVIA claims data indicates that many diagnosed, identifiable eligible patients do not receive prescriptions for intra-muscular injectables.
Currently, we estimate only between 20% to 30% of patients obtain more than one pack (containing two devices) per year today. 25 US Market Expansion Opportunity While we believe the existing epinephrine intra-muscular injectables market is a large commercial opportunity for neffy with multiple independent opportunities for further growth, IQVIA claims data indicates that many diagnosed, identifiable eligible patients do not receive prescriptions for intra-muscular injectables.
To achieve this goal, we have assembled a management team with extensive experience in the development and commercialization of drugs, such as recently approved nasal sprays NARCAN (naloxone nasal spray) and VALTOCO (diazepam nasal spray). Our company was founded by Richard Lowenthal, M.S., MSEL, Robert Bell, Ph.D. and Sarina Tanimoto, M.D., M.B.A. Pratik Shah, Ph.D. was our first external investor.
To achieve this goal, we have assembled a management team with extensive experience in the development and commercialization of drugs, such as recently approved nasal sprays NARCAN (naloxone nasal spray) and VALTOCO (diazepam nasal spray). Our company was founded by Richard Lowenthal, M.S., MSEL, Robert Bell, Ph.D. and Sarina Tanimoto, M.D., MBA. Pratik Shah, Ph.D. was our first external investor.
We believe the availability of neffy could drive increased device uptake among the existing 3.3 million patients currently filling epinephrine injection device prescriptions, adoption by the approximately 2.5 million patient that receive, but do not fill their prescription, and the 11 million patients diagnosed and managed by physicians who do not currently have an epinephrine auto-injector, especially those incorrectly using antihistamines as a substitute.
We believe the availability of neffy could drive increased device uptake among the existing 3.2 million patients currently filling epinephrine injection device prescriptions, adoption by the approximately 3.3 million patient that receive, but do not fill their prescription, and the 13.5 million patients diagnosed and managed by physicians who do not currently have an epinephrine auto-injector, especially those incorrectly using antihistamines as a substitute.
Health insurers surveyed have indicated that neffy is perceived as differentiated brand from epinephrine auto-injector products, with its needle-free route of administration and increased likelihood of being carried as the most important product attributes. Based on these analyses and our planned contracting strategy, we believe payers can support favorable and broad market access for neffy .
Health insurers surveyed have indicated that neffy is perceived as differentiated brand from epinephrine auto-injector products, with its needle-free route of administration and increased likelihood of being carried as the most important product attributes. Based on these analyses and our planned contracting strategy, we believe payors can support favorable and broad market access for neffy .
Five-year and three-year exclusivity will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and efficacy. 33 Pediatric exclusivity is another type of non-patent market exclusivity in the United States.
Five-year and three-year exclusivity will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and efficacy. 39 Pediatric exclusivity is another type of non-patent market exclusivity in the United States.
Injection-like absorption even with nasal congestion neffy reaches exposures comparable to approved injectable products even after induction of moderate to severe nasal rhinitis and/or edema (e.g., nasal congestion) Shelf-life at least comparable to injection products, but also with high temperature stability Drug stability studies show that n effy has a shelf-life at least comparable to the 18 month shelf-life of EpiPen, but with high temperature stability, based on stability data from the 2.0 mg dose of neffy for 12 months and the 1.0 mg dose of neffy for 24 months. neffy remains within specifications even when exposed to temperatures of 50 o C (122 o F) for at least three months, or temperatures of 40 o C (104 o F) for at least six months.
Injection-like absorption even with nasal congestion neffy reaches exposures comparable to approved injectable products even after induction of moderate to severe nasal rhinitis and/or edema (e.g., nasal congestion) 20 Shelf-life at least comparable to injection products, but also with high temperature stability Drug stability studies show that neffy has a shelf-life at least comparable to the 18 month shelf-life of EpiPen, but with high temperature stability, based on stability data from the 2.0 mg dose of neffy for 12 months and the 1.0 mg dose of neffy for 24 months. neffy remains within specifications even when exposed to temperatures of 50 o C (122 o F) for at least three months, or temperatures of 40 o C (104 o F) for at least six months.
We anticipate that in certain markets additional clinical trials of neffy may be required to obtain regulatory approval and/or ensure market access. 22 Competition Our industry is highly competitive and subject to rapid technological changes. Our potential competitors include large pharmaceutical and biotechnology companies, specialty pharmaceutical and generic drug companies, academic institutions, government agencies and research institutions.
We anticipate that in certain markets additional clinical trials of neffy may be required to obtain regulatory approval and/or ensure market access. 28 Competition Our industry is highly competitive and subject to rapid technological changes. Our potential competitors include large pharmaceutical and biotechnology companies, specialty pharmaceutical and generic drug companies, academic institutions, government agencies and research institutions.
Aptar produces devices in France and we believe Aptar has sufficient capacity to satisfy our long-term requirements. The patent for the Aptar unit dose nasal spray device expired in early 2020, and we believe there will be generic supplies available soon after launch. 23 Manufacturing drug product for neffy is conducted by Renaissance Pharmaceuticals, Inc.
Aptar produces devices in France and we believe Aptar has sufficient capacity to satisfy our long-term requirements. The patent for the Aptar unit dose nasal spray device expired in early 2020, and we believe there will be generic supplies available soon after launch. 29 Manufacturing drug product for neffy is conducted by Renaissance Pharmaceuticals, Inc.
The medical affairs team will also collaborate with the commercial team to help payers fully understand neffy’s value proposition and the limitations associated with needle injectors. We also plan to begin to raise awareness and support meaningful education through partnership with patient advocacy groups and medical societies as well as a disease education campaign including through social media and digital.
The medical affairs team will also collaborate with the commercial team to help payors fully understand neffy’s value proposition and the limitations associated with needle injectors. We also plan to begin to raise awareness and support meaningful education through partnership with patient advocacy groups and medical societies as well as a disease education campaign including through social media and digital.
Dodecyl maltoside or Intravail is purchased through our license agreement with Aegis Therapeutics, Inc. from two manufacturers, Dr. Reddy Laboratories and Inalco, which are based in India and Italy, respectively. The unit dose sprayer device used to delivery drug product in neffy is produced by Aptar Pharma (“Aptar”).
Dodecyl maltoside or Intravail is purchased through our license agreement with Aegis Therapeutics, LLC from two manufacturers, Dr. Reddy Laboratories and Inalco, which are based in India and Italy, respectively. The unit dose sprayer device used to delivery drug product in neffy is produced by Aptar Pharma (“Aptar”).
We are also not aware of any “no needle, no injection” epinephrine product candidate for the pediatric population that is in clinical development. We are aware of several companies developing higher dose intranasal candidates including Bryn Pharma, Hikma Pharmaceuticals, Inc. (previously INSYS Therapeutics, Inc.), Nasus Pharma and Orexo AB.
We are also not aware of any “no needle, no injection” epinephrine product candidate for the pediatric population that is in clinical development. We are aware of several companies developing higher dose intranasal candidates including Bryn Pharma, Hikma Pharmaceuticals, Inc. (previously INSYS Therapeutics, Inc.), Nasus Pharma, Orexo AB and Belhaven BioPharma.
In June 2017, the FDA approved Symjepi ™ epinephrine injection, which is a pre-filled syringe for the same indication. These injection devices were approved by the FDA without pharmacokinetic data based on an assumption that injections and devices were all effectively the same as the reference listed drug of intra-muscular injection with a needle and syringe.
In June 2017, the FDA approved Symjepi ™ epinephrine injection, which is a pre-filled syringe for the same indication. These injection devices were approved by the FDA without PK data based on an assumption that injections and devices were all effectively the same as the reference listed drug of intra-muscular injection with a needle and syringe.
We believe the attractiveness and meaningful differentiation of neffy across both physicians and payers will stimulate a high patient and parent desire to switch to or return to managing their condition with neffy . We intend to secure affordable market access for all consumers by optimizing contracting, co-pay support and distribution of neffy .
We believe the attractiveness and meaningful differentiation of neffy across both physicians and payors will stimulate a high patient and parent desire to switch to or return to managing their condition with neffy . We intend to secure affordable market access for all consumers by optimizing contracting, co-pay support and distribution of neffy .
Even if such data and information are submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. 30 If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.
Even if such data and information are submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. 36 If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.
In comparison, neffy is perceived by patients and parents as a potentially “game changing” device that, if approved, could improve the management of severe Type I allergic reactions by addressing the current limitations of epinephrine intra-muscular injectable devices. 14 Clinical Development of neffy neffy is designed to provide injection-like absorption of epinephrine at a 1.0 or 2.0 mg dose comparable to 0.3 mg injection, in a small, easy-to-carry, easy-to-use, rapidly administered and reliable nasal spray.
In comparison, neffy is perceived by patients and parents as a potentially “game changing” device that, if approved, could improve the management of severe Type I allergic reactions by addressing the current limitations of epinephrine intra-muscular injectable devices. 16 Clinical Development of neffy neffy is designed to provide injection-like absorption of epinephrine at a 2.0 or 1.0 mg dose comparable to 0.3 mg or 0.15 mg injection, in a small, easy-to-carry, easy-to-use, rapidly administered and reliable nasal spray.
Other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval. 31 The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
Other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval. 37 The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
In our market research, parents and people with current or prior epinephrine auto-injector prescriptions were asked if and when they would adopt a new nasal spray device product such as neffy . • A majority indicated they would adopt neffy within three months of it coming to market, • 69% of patients indicated they would use neffy sooner than their current auto-injector device, • 65 to 72% of patients indicated that they would use neffy first instead of an over-the-counter antihistamine • 88% reported they would be more willing to use neffy in public.
In our market research, parents and people with current or prior epinephrine auto-injector prescriptions were asked if and when they would adopt a new nasal spray device product such as neffy . • A majority indicated they would adopt neffy within three months of it coming to market, • 81% of patients indicated they would use neffy sooner than their current auto-injector device, • 72% of patients indicated that they would use neffy first instead of an over-the-counter antihistamine • 88% reported they would be more willing to use neffy in public.
However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labelling. 32 Hatch-Waxman Act Section 505 of the FDCA describes three types of marketing applications that may be submitted to the FDA to request marketing authorization for a new drug.
However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labelling. 38 Hatch-Waxman Act Section 505 of the FDCA describes three types of marketing applications that may be submitted to the FDA to request marketing authorization for a new drug.
We co-own or exclusively license the patents and patent applications relating to our intranasal epinephrine product candidates. As of December 31, 2022, our patent portfolio consisted of issued patents and pending patent applications that we co-own or exclusively license from Aegis Therapeutics LLC in the United States and other countries throughout the world.
We co-own or exclusively license the patents and patent applications relating to our intranasal epinephrine product candidates. As of December 31, 2023, our patent portfolio consisted of issued patents and pending patent applications that we co-own or exclusively license from Aegis Therapeutics LLC in the United States and other countries throughout the world.
In the first quarter of 2023, we entered into an agreement with Recordati to terminate our prior agreement with it and reacquire Recordati’s rights to develop and commercialize neffy . 20 Commercial Strategy We believe that the epinephrine market is a highly consumer driven market .
In the first quarter of 2023, we entered into an agreement with Recordati to terminate our prior agreement with it and reacquire Recordati’s rights to develop and commercialize neffy . 26 Commercial Strategy We believe that the epinephrine market is a highly consumer driven market .
We are not aware of any other company that has a “no needle, no injection” epinephrine product candidate in clinical development in the United States that has demonstrated PKs bracketed by the approved injection products for all pharmacokinetic parameters requested by the FDA.
We are not aware of any other company that has a “no needle, no injection” epinephrine product candidate in clinical development in the United States that has demonstrated PKs bracketed by the approved injection products for all PK parameters requested by the FDA.
In addition, HIPAA, as amended by Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), imposes certain requirements on covered entities, which include certain healthcare providers, health plans and healthcare clearinghouses, and their business associates and covered subcontractors that receive or obtain protected health information in connection with providing a service on behalf of a covered entity relating to the privacy, security and transmission of individually identifiable health information. 34 The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals (such as physicians assistants and nurse practitioners), and teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members.
In addition, HIPAA, as amended by Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), imposes certain requirements on covered entities, which include certain healthcare providers, health plans and healthcare clearinghouses, and their business associates and covered subcontractors that receive or obtain protected health information in connection with providing a service on behalf of a covered entity relating to the privacy, security and transmission of individually identifiable health information. 40 The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals (such as physicians assistants and nurse practitioners), and teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members.
In addition, under FDA regulations, combination products such as neffy are subject to cGMP requirements applicable to both drugs and devices, including the Quality System Regulations applicable to medical devices. 27 U.S. Drug Development Process In the United States, the FDA regulates drugs under the FDCA, and implementing regulations.
In addition, under FDA regulations, combination products such as neffy are subject to cGMP requirements applicable to both drugs and devices, including the Quality System Regulations applicable to medical devices. 33 U.S. Drug Development Process In the United States, the FDA regulates drugs under the FDCA, and implementing regulations.
We expect this to be especially true for neffy , given that 100% of the physicians surveyed in our quantitative market research studies indicated that they would prescribe neffy if asked by a patient and approximately 70% of physicians would recommend neffy .
We expect this to be especially true for neffy , given that 99% of the physicians surveyed in our quantitative market research studies indicated that they would prescribe neffy if asked by a patient and approximately 70% of physicians would recommend neffy .
In addition, we believe that the potential for neffy to address the limitations of auto-injectors will allow us to expand the market opportunity for neffy over time to include the broader population of approximately 2.5 million patients who have received a prescription, but either refused or discontinued treatment in the last three years, as well as the approximately 11 million patients who are diagnosed and under the care of physicians, but have not been prescribed an epinephrine intra-muscular injectable. • Commercialize neffy outside of the United States with our partners .
In addition, we believe that the potential for neffy to address the limitations of auto-injectors will allow us to expand the market opportunity for neffy over time to include the broader population of approximately 3.3 million patients who have received a prescription, but either refused or discontinued treatment, as well as the approximately 13.5 million patients who are diagnosed and under the care of physicians, but have not been prescribed an epinephrine intra-muscular injectable over the last three-years. • Commercialize neffy outside of the United States with our partners .
Notwithstanding their widespread lack of use, we estimate that net sales of intra-muscular injectable products approved for outpatient use in the United States was approximately $1 billion in 2021 among the approximately 3.3 million patients who filled a prescription. 6 Our Approach neffy TM is an investigational drug currently in clinical trials for the emergency treatment of allergic reactions (type I) including anaphylaxis. neffy TM is not approved by the FDA, EMA or other health authorities. 7 neffy is designed to address the shortcomings of intra-muscular injectable devices. neffy is a convenient “no needle, no injection,” solution designed to be easier to carry, more reliable and easier to administer, without the aversion, safety concerns and fear and pain of needles associated with intra-muscular injectables.
Notwithstanding their widespread lack of use, we estimate that net sales of intra-muscular injectable products approved for outpatient use in the United States was approximately $1 billion in 2023 among the approximately 3.2 million patients who filled a prescription. 7 Our Approach neffy is an investigational drug currently in clinical trials for the emergency treatment of allergic reactions (type I) including anaphylaxis. neffy is not approved by the FDA, EMA or other health authorities. 8 neffy is designed to address the shortcomings of intra-muscular injectable devices. neffy is a convenient “no needle, no injection,” solution designed to be easier to carry, more reliable and easier to administer, without the aversion, safety concerns and fear and pain of needles associated with intra-muscular injectables.
Congress is considering additional health reform measures. 36 Moreover, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S.
Congress is considering additional health reform measures. 42 Moreover, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S.
Through these efforts, combined with direct-to-consumer omnichannel strategies to drive awareness and patients asking for neffy , we believe we can quickly and efficiently reach a majority of the approximately 3.3 million patients in the United States who filled a prescription for an epinephrine intra-muscular injectable device in 2021.
Through these efforts, combined with direct-to-consumer omnichannel strategies to drive awareness and patients asking for neffy , we believe we can quickly and efficiently reach a majority of the approximately 3.2 million patients in the United States who filled a prescription for an epinephrine intra-muscular injectable device in 2023.
Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 29 U.S.
Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 35 U.S.
As a result, many of the approximately 25 to 40 million patients at risk of severe Type I allergic reactions do not receive or fill prescriptions for intra-muscular injectables.
As a result, many of the approximately 40 million patients at risk of severe Type I allergic reactions do not receive or fill prescriptions for intra-muscular injectables.
If approved, we plan to establish a distribution channel in the United States for the commercialization of neffy . We expect to sell neffy to wholesalers, who, in turn, will sell our neffy to retailors and other customers.
If approved, we plan to establish a distribution channel in the United States for the commercialization of neffy . We expect to sell neffy to wholesalers, who, in turn, will sell our neffy to retailers and other customers.
Furthermore, neffy also showed zero dosing errors in two human factor validation studies involving 150 subjects when used by trained adults or trained children across multiple demographic groups, as well as when used by passers-byers with no prior experience or training with an epinephrine device. 16 Key features of neffy demonstrated in our clinical, human factors or stability studies include: Clinical Feature Supporting Clinical Data Comparable PKs at a low dose of epinephrine C max , t max and AUCs were within the range of approved intra-muscular injection products with a low intranasal dose of 2.0 mg n effy (people >30 kg in weight) and 1.0 mg n effy (people 15 – 30 kg weight).
Furthermore, neffy also showed zero dosing errors in two human factor validation studies involving 150 subjects when used by trained adults or trained children across multiple demographic groups, as well as when used by passers-byers with no prior experience or training with an epinephrine device. 19 Key features of neffy demonstrated in our clinical, human factors or stability studies include: Clinical Feature Supporting Clinical Data Comparable PKs to epinephrine C max , t max and AUCs were within the range of approved intra-muscular injection products with a low intranasal dose of 2.0 mg neffy (people >30 kg in weight) and 1.0 mg neffy (people 15 – 30 kg weight).
Furthermore, 100% of the physicians surveyed stated they would prescribe if their patient asked for neffy, indicating that neffy prescriptions would likely be highly driven by patient preference and awareness of neffy .
Furthermore, 99% of the physicians surveyed stated they would prescribe if their patient asked for neffy , indicating that neffy prescriptions would likely be highly driven by patient preference and awareness of neffy .
For more information regarding the risks related to our intellectual property, see “ Risk Factors—Risks Related to Our Intellectual Property. ” 24 We also seek to protect our intellectual property in part by entering into confidentiality agreements with companies with whom we share proprietary and confidential information in the course of business discussions, and by having confidentiality terms in our agreements with our employees, consultants, scientific advisors, clinical investigators, and other collaborators and contractors and also by requiring our employees, commercial contractors, and certain consultants and investigators, to enter into invention assignment agreements that grant us ownership of any discoveries or inventions made by them while in our employ.
For this and more comprehensive risks related to our intellectual property, please see “ Risk Factors—Risks Related to Our Intellectual Property. ” We also seek to protect our intellectual property in part by entering into confidentiality agreements with companies with whom we share proprietary and confidential information in the course of business discussions, and by having confidentiality terms in our agreements with our employees, consultants, scientific advisors, clinical investigators, and other collaborators and contractors and also by requiring our employees, commercial contractors, and certain consultants and investigators, to enter into invention assignment agreements that grant us ownership of any discoveries or inventions made by them while in our employ.
No meaningful pain or irritation after administration Visual analogue scale scores were an average of 5 to 8 on a 100 mm scale, and show no meaningful pain (or burning or stinging sensation) after administration, attributable to n effy being an aqueous formulation. There is also no irritation observed based on formal scoring.
No meaningful pain or irritation after administration Visual analogue scale scores were an average of 5 to 8 on a 100 mm scale, and show no meaningful pain (or burning or stinging sensation) after administration, attributable to neffy being an aqueous formulation. There is also no irritation observed based on formal scoring.
Ex-US Market Opportunity • Outside of the United States, we estimate that there are an additional 15 million patients in Europe, and over 30 million patients in Asia including China and Japan, that experience Type I allergic reactions that are clinically appropriate for being prescribed neffy . • In 2021, epinephrine intra-muscular injectable sales outside the United States were approximately $250 million based on IQVIA data.
Ex-US Market Opportunity • Outside of the United States, we estimate that there are an additional 15 million patients in Europe, and over 30 million patients in Asia including China and Japan, that experience Type I allergic reactions that are clinically appropriate for being prescribed neffy . • In 2022, epinephrine intra-muscular injectable sales outside the United States were approximately $300 million based on IQVIA data.
Of this group, approximately 16 million people have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, but only 3.3 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector.
Of this group, approximately 20 million people have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, but only 3.2 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector.
Needle containing intra-muscular injection products are known to be painful and cause reluctance to dose. Easy to use No critical dosing errors during self-administration with 2.0 mg n effy by type I allergy adult subjects (EPI-17).
Needle containing intra-muscular injection products are known to be painful and cause reluctance to dose. Easy to use No critical dosing errors during self-administration with 2.0 mg neffy by type I allergy adult subjects (EPI-17).
From 2007 to 2021, the number of epinephrine intra-muscular injectable devices sold in the United States has increased by approximately 5% annually based on IQVIA unit sales data, primarily due to the increasing size of the overall population affected by severe Type I allergies, led by food-based allergies. • Potential promotional lift due to new marketing and education efforts by a branded product such as neffy .
From 2010 to 2023, the number of epinephrine intra-muscular injectable devices sold in the United States has increased by approximately 6.5% annually based on IQVIA unit sales data, primarily due to the increasing size of the overall population affected by severe Type I allergies, led by food-based allergies. • Potential promotional lift due to new marketing and education efforts by a branded product such as neffy .
Mr. Lowenthal, our Co-Founder and Chief Executive Officer, has more than 25 years of biotechnology and pharmaceutical development experience including leading the regulatory approvals of VALTOCO (diazepam nasal spray) and NARCAN (naloxone nasal spray). Dr.
Mr. Lowenthal, our Co-Founder, President, Chief Executive Officer, and one of our directors, has more than 25 years of biotechnology and pharmaceutical development experience including leading the regulatory approvals of VALTOCO (diazepam nasal spray) and NARCAN (naloxone nasal spray). Dr.
We intend to submit regulatory filings equivalent to an NDA in Japan and China in collaboration with Alfresa Pharma and Pediatrix Therapeutics, respectively, to whom we have granted exclusive licenses in those regions for the development and commercialization of neffy . • Conduct additional studies of neffy to address additional Type I allergic reactions .
We intend to submit regulatory filings by year end 2024 equivalent to an NDA in Japan and China in collaboration with Alfresa Pharma and Pediatrix Therapeutics, respectively, to whom we have granted exclusive licenses in those regions for the development and commercialization of neffy . • Conduct additional studies of neffy to address additional Type I allergic reactions .
Existing US Market Opportunity We estimate approximately 25 to 40 million people in the United States have experienced Type I allergic reactions.
Existing US Market Opportunity We estimate approximately 40 million people in the United States have experienced Type I allergic reactions.
Either party may terminate the agreement (1) for uncured material breach of the other party, (2) upon notice for insolvency-related events of the other party that are not discharged within a defined time period, (3) on a product-by-product basis if the manufacture, distribution or sale would materially contravene any applicable law, (4) by providing the requisite notice if (a) we have not submitted a regulatory filing for any Renaissance Product in the U.S. on or before June 30, 2022, (b) the authorization and approval to distribute or sell Renaissance Product in the U.S. is not granted on or before the target U.S. launch date, (c) the authorization and approval representing more than a targeted number of units of Renaissance Product sold in the U.S. during the last calendar year is withdrawn by the FDA, or (d) we decided in our sole discretion to cease commercializing the Renaissance Product in the U.S., (5) in the case of a force majeure event that continues for six months or more, or (6) a violation by the other party of trade control or anti-corruption laws.
Either party may terminate the agreement (1) for uncured material breach of the other party, (2) upon notice for insolvency-related events of the other party that are not discharged within a defined time period, (3) on a product-by-product basis if the manufacture, distribution or sale would materially contravene any applicable law, (4) by providing the requisite notice if (a) we have not submitted a regulatory filing for any Renaissance Product in the U.S. on or before June 30, 2022, (b) the authorization and approval to distribute or sell Renaissance Product in the U.S. is not granted on or before the target U.S. launch date, (c) the authorization and approval representing more than a targeted number of units of Renaissance Product sold in the U.S. during the last calendar year is withdrawn by the FDA, or (d) we decided in our sole discretion to cease commercializing the Renaissance Product in the U.S., (5) in the case of a force majeure event that continues for six months or more, or (6) a violation by the other party of trade control or anti-corruption laws. 32 Government Regulation and Product Approval As a pharmaceutical company that operates in the United States, we are subject to extensive regulation.
Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year pursuant to the Budget Control Act of 2011which went into effect on April 1, 2013, and due to subsequent legislative amendments, will remain in effect until 2031, unless additional Congressional action is taken.
Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year pursuant to the Budget Control Act of 2011 which went into effect on April 1, 2013, and due to subsequent legislative amendments, will remain in effect until 2032, unless additional Congressional action is taken.
For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.
For example, the EU provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.
We plan to reach and support patients directly through efficient direct-to-consumer advertising after educating professional physician practices and securing appropriate payer coverage for neffy . • Targeting the approximately 2.5 million former patients that either do not fill their epinephrine intra-muscular injectables prescriptions or whose prescriptions have recently lapsed .
We plan to reach and support patients directly through efficient direct-to-consumer advertising after educating professional physician practices and securing appropriate payor coverage for neffy . • Targeting the approximately 3.3 million former patients that either do not fill their epinephrine intra-muscular injectables prescriptions or whose prescriptions have recently lapsed .
The needle-free, portable, easy-to-use and potentially safer clinical profile of neffy supported by pharmacokinetic and pharmacodynamic data could enable the broader adoption of epinephrine in the outpatient setting for these other indications.
The needle-free, portable, easy-to-use and potentially safer clinical profile of neffy supported by PK and PD data could enable the broader adoption of epinephrine in the outpatient setting for these other indications.
In our clinical trials, we observed that neffy has comparable pharmacokinetics (“PK”) and pharmacodynamics (“PD”) compared to marketed epinephrine injectables. • Needle-free, easy-to-use, pocket-sized and highly reliable nasal spray. neffy is easier to carry than approved intra-muscular injectables because it is pocket-sized, increasing the likelihood that the device is available for use in an emergency.
In our clinical trials, we observed that neffy has comparable PK and PD compared to marketed epinephrine injectables. • Needle-free, easy-to-use, pocket-sized and highly reliable nasal spray. neffy is easier to carry than approved intra-muscular injectables because it is pocket-sized, increasing the likelihood that the device is available for use in an emergency.
Approximately 80% of epinephrine auto-injectors prescribed in the United States for outpatient use are the 0.3 mg dose level for persons greater than 30 kg in weight, approximately 15% contain doses of 0.15 mg for persons between 15 to 30 kg and less than 5% contain 0.1 mg doses for persons less than 15 kg.
Approximately 77% of epinephrine auto-injectors prescribed in the United States in 2023 for outpatient use are the 0.3 mg dose level for persons greater than 30 kg in weight, approximately 22% contain doses of 0.15 mg for persons between 15 to 30 kg and 1% contain 0.1 mg doses for persons less than 15 kg.
In contrast, for patients self-administering devices, which involved 132 subjects dosed for each of EpiPen and Symjepi, approximately 14% of subjects dosed with EpiPen (auto-injector) and 2% of subjects dosed with Symjepi (pre-filled needle-in-syringe) experienced a potential blood vessel injection leading to a rapid bolus dose of epinephrine, which could lead to serious side effects including cardiovascular events and cerebral hemorrhage according to the FDA EpiPen label.
In contrast, for patients self-administering devices, which involved 132 subjects dosed with EpiPen, approximately 14% of subjects dosed with EpiPen (auto-injector) experienced a potential blood vessel injection leading to a rapid bolus dose of epinephrine, which could lead to serious side effects including cardiovascular events and cerebral hemorrhage according to the FDA EpiPen label.
Furthermore, we also plan to pursue additional expansion in our pediatric labeling with neffy and are conducting a single-arm pharmacokinetic study in subjects 4 to 18 years of age. The interim pediatric data including subjects greater than 30 kg in weight is included in our initial NDA.
Furthermore, we also plan to pursue additional expansion in our pediatric labeling with neffy and have completed a single-arm PK study in subjects 4 to 18 years of age. The interim pediatric data including subjects greater than 30 kg in weight is included in our initial NDA.
In our market research of 100 former patients who refused to fill or renew a prescription, approximately 75% indicated a willingness to return to the market and request neffy if approved.
In our market research of 88 former patients who refused to fill or renew a prescription, approximately 89% indicated a willingness to return to the market and request neffy if approved.
We plan to submit a post-approval variation to EMA for the 1.0 mg neffy following the potential approval of the 2.0 mg neffy dose. Our partners in Japan and China expect that they will file for regulatory approval in their respective regions at end of 2023 or early 2024 following our anticipated FDA approval of neffy .
We plan to submit a post-approval variation to EMA for the 1.0 mg neffy following the potential approval of the 2.0 mg neffy dose. Our partners in Japan and China expect that they will file for regulatory approval in their respective regions in 2024 following the potential FDA approval of neffy .
In Europe and Japan, sales of epinephrine injectable devices are approximately $160 million.
In Europe and Japan, sales of epinephrine injectable devices are approximately $220 million.
During our pre-NDA meeting in mid-2021, FDA agreed that bracketing based on the primary parameters of C max , t max and early partial AUCs from the range of PKs observed in listed epinephrine injection products was the best approach to ensure efficacy and safety, while bracketing by AUC 0-t was considered an important parameter to ensure safety.
The FDA agreed that bracketing based on the primary parameters of C max , t max and early partial AUCs from the range of PKs observed in listed epinephrine injection products was the best approach to ensure efficacy and safety, while bracketing by AUC 0-t was considered an important parameter to ensure safety.

… 141 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

155 edited+43 added−30 removed594 unchanged
Biggest changeWe may also experience numerous unforeseen events during our clinical trials that could delay or prevent our ability to receive marketing approval or commercialize neffy or any future product candidates we develop, including: • regulators, or IRBs or other reviewing bodies may not authorize us or our investigators to commence a clinical trial, or to conduct or continue a clinical trial at a prospective or specific trial site; • we may not reach an agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • a delay in receiving study or clinical trial material from outside the United States; • the number of subjects or patients required for clinical trials of neffy in an indication or any future product candidate may be larger than we anticipate, enrollment in these clinical trials may be insufficient or slower than we anticipate, and the number of clinical trials being conducted at any given time may be high and result in fewer available patients for any given clinical trial, or patients may drop out of these clinical trials at a higher rate than we anticipate; • our third-party contractors, including those manufacturing neffy or any future product candidates or conducting clinical trials on our behalf, may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • we may have to amend clinical trial protocol(s) submitted to regulatory authorities or conduct additional studies to reflect changes in regulatory requirements or guidance, which we may be required to resubmit to an IRB and regulatory authorities for re-examination; • unforeseen safety events may occur during the course of a clinical trial and these events may result in the temporary suspension or termination of a clinical trial, or require urgent safety measures or restrictions to protect human subjects during the conduct of a clinical trial; • regulators, IRBs or other reviewing bodies may fail to approve or subsequently find fault with the manufacturing processes or facilities of third-party manufacturers with which we have entered and may enter into agreement for clinical and commercial supplies, or the supply or quality of neffy or any future product candidate or other materials necessary to conduct clinical trials of neffy or any future product candidates may be insufficient, inadequate or not available at an acceptable cost, or we may experience interruptions in supply; and • the potential for approval policies or regulations of the FDA, the EMA or any other applicable foreign regulatory agencies to significantly change in a manner rendering our clinical data insufficient for approval. 49 Regulators, IRBs of the institutions in which clinical trials are being conducted, or data monitoring committees may suspend or terminate a clinical trial due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to appear to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
Biggest changeWe may also experience numerous unforeseen events during our clinical trials that could delay or prevent our ability to receive marketing approval or commercialize neffy or any future product candidates we develop, including: • regulators, or IRBs or other reviewing bodies may not authorize us or our investigators to commence a clinical trial, or to conduct or continue a clinical trial at a prospective or specific trial site; • we may not reach an agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • a delay in receiving study or clinical trial material from outside the United States; • the number of subjects or patients required for clinical trials of neffy in an indication or any future product candidate may be larger than we anticipate, enrollment in these clinical trials may be insufficient or slower than we anticipate, and the number of clinical trials being conducted at any given time may be high and result in fewer available patients for any given clinical trial, or patients may drop out of these clinical trials at a higher rate than we anticipate; • our third-party contractors, including those manufacturing neffy or any future product candidates or conducting clinical trials on our behalf, may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • we may have to amend clinical trial protocol(s) submitted to regulatory authorities or conduct additional studies to reflect changes in regulatory requirements or guidance, which we may be required to resubmit to an IRB and regulatory authorities for re-examination; • unforeseen safety events may occur during the course of a clinical trial and these events may result in the temporary suspension or termination of a clinical trial, or require urgent safety measures or restrictions to protect human subjects during the conduct of a clinical trial; • regulators, IRBs or other reviewing bodies may fail to approve or subsequently find fault with the manufacturing processes or facilities of third-party manufacturers with which we have entered and may enter into agreement for clinical and commercial supplies, or the supply or quality of neffy or any future product candidate or other materials necessary to conduct clinical trials of neffy or any future product candidates may be insufficient, inadequate or not available at an acceptable cost, or we may experience interruptions in supply; and • the potential for approval policies or regulations of the FDA, the EMA or any other applicable foreign regulatory agencies to significantly change in a manner rendering our clinical data insufficient for approval.
Furthermore, while we intend to protect our intellectual property rights in our expected significant markets, we cannot ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market our product candidates.
Furthermore, while we intend to protect our intellectual property rights in our expected significant markets, we cannot ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market our product candidates.
In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act; • federal civil monetary penalties laws impose civil fines for, among other things, the offering or transfer of remuneration to a Medicare or state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by Medicare or a state healthcare program, unless an exception applies; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) which prohibits, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, of any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless or the payor (e.g., public or private), willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services; like the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the federal Physician Payment Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the government information related to payments or other “transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their respective implementing regulations, which impose obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” and their covered subcontractors that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; 70 • federal price reporting laws require manufactures to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on approved products; • federal and state consumer protection and unfair competition laws broadly regulate marketplace activities and activities that potentially harm consumers; and • analogous state laws and regulations, such as state anti-kickback and false claims laws, that may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers; some state laws that require biotechnology companies to comply with the industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government and may require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; some state laws that require biotechnology companies to report information on the pricing of certain drug products; and some state and local laws require the registration or pharmaceutical sales representatives.
In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act; • federal civil monetary penalties laws impose civil fines for, among other things, the offering or transfer of remuneration to a Medicare or state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by Medicare or a state healthcare program, unless an exception applies; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) which prohibits, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, of any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless or the payor (e.g., public or private), willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services; like the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the federal Physician Payment Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the government information related to payments or other “transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their respective implementing regulations, which impose obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” and their covered subcontractors that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; 76 • federal price reporting laws require manufactures to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on approved products; • federal and state consumer protection and unfair competition laws broadly regulate marketplace activities and activities that potentially harm consumers; and • analogous state laws and regulations, such as state anti-kickback and false claims laws, that may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers; some state laws that require biotechnology companies to comply with the industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government and may require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; some state laws that require biotechnology companies to report information on the pricing of certain drug products; and some state and local laws require the registration or pharmaceutical sales representatives.
Our future capital requirements depend on many factors, including: • the scope, progress, results and costs of researching and developing neffy for the emergency treatment of Type I allergic reactions and potential additional indications, as well as any future product candidates we may develop; • the timing of, and the costs involved in, obtaining regulatory approval for the marketing of neffy for the emergency treatment of Type I allergic reactions and potential additional indications, and any future product candidates we may develop and pursue; • the number of future product candidates that we may pursue and their development requirements, if any; • if approved, the costs of commercialization activities for neffy for any approved indications, or the similar cost of any other product candidate that receives regulatory approval to the extent such costs are not the responsibility of any current or future licensing and collaboration partners, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval, revenue received from commercial sales of neffy for any approved indications or from future product candidates, if any; • the amount and timing of potential royalty and milestone payments to our current or future licensing and collaboration partners; • the receipt of licensing fees, royalties and potential milestone payments under our current or future out-licensing arrangements; • the extent to which we in-licenses or acquire rights to other products, product candidates or technologies; • our headcount growth and associated costs as we expand our personnel, including personnel to support our product candidate development and potential future commercialization efforts and help us comply with our obligations as a public company; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the ongoing costs of operating as a public company.
Our future capital requirements depend on many factors, including: • the scope, progress, results and costs of researching and developing neffy for the emergency treatment of Type I allergic reactions and potential additional indications, as well as any future product candidates we may develop; • the timing of, and the costs involved in, obtaining regulatory approval for the marketing of neffy for the emergency treatment of Type I allergic reactions and potential additional indications, and any future product candidates we may develop and pursue; • the number of future product candidates that we may pursue and their development requirements, if any; • if approved, the costs of commercialization activities for neffy for any approved indications, or the similar cost of any other product candidate that receives regulatory approval to the extent such costs are not the responsibility of any current or future licensing and collaboration partners, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval, revenue received from commercial sales of neffy for any approved indications or from future product candidates, if any; • the amount and timing of potential royalty and milestone payments to our current or future licensing and collaboration partners; • the receipt of licensing fees, royalties and potential milestone payments under our current or future out-licensing arrangements; • the extent to which we in-license or acquire rights to other products, product candidates or technologies; • our headcount growth and associated costs as we expand our personnel, including personnel to support our product candidate development and potential future commercialization efforts and help us comply with our obligations as a public company; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the ongoing costs of operating as a public company.
If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to us, we may be subject to significant penalties, including administrative, civil and criminal penalties, damages, fines, exclusion from governmental health care programs, a corporate integrity agreement or other agreement to resolve allegations of non-compliance, imprisonment, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our financial results.
If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to us, we may be subject to significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, exclusion from governmental health care programs, a corporate integrity agreement or other agreement to resolve allegations of non-compliance, imprisonment, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our financial results.
Adverse differences between preliminary or interim data and final data could significantly harm our reputation and business prospects. 50 neffy or any future product candidate may cause undesirable side effects, adverse events, or have other properties that could delay or prevent its regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following regulatory approval, if obtained.
Adverse differences between preliminary or interim data and final data could significantly harm our reputation and business prospects. neffy or any future product candidate may cause undesirable side effects, adverse events, or have other properties that could delay or prevent its regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following regulatory approval, if obtained.
In addition, new debt financing, if available, may result in fixed payment obligations and may involve agreements that include restrictive covenants that further limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, that could adversely impact our ability to conduct our business.
In addition, new debt financing, if available, may result in fixed payment obligations and may involve agreements that include restrictive covenants that further limit our ability to take specific actions, such as incurring additional debt, making capital expenditures, creating liens, redeeming stock or declaring dividends, which could adversely impact our ability to conduct our business.
We co-own or exclusively license patent applications in our portfolio relating to our product candidates that are pending at the patent offices in the United States, Europe, Japan, and other foreign jurisdictions, however, we cannot predict: • if and when patents may issue based on the patent applications we own, co-own or exclusively license; • the scope of protection of any patent issuing based on the patent applications we own, co-own or exclusively license; • whether the claims of any patent issuing based on the patent applications we own, co-own or exclusively license will provide protection against competitors, • whether or not third parties will find ways to invalidate or circumvent our patent rights; • whether or not others will obtain patents claiming aspects similar to those covered by the patent applications we own, co-own or exclusively license; • whether we will need to initiate litigation or administrative proceedings to enforce and/or defend our patent rights which will be costly whether we win or lose; • whether the patent applications that we own, co-own or exclusively license will result in issued patents with claims that cover our product candidates or uses thereof; and/or • whether we may experience patent office interruption or delays to our ability to timely secure patent coverage to our product candidates.
We co-own or exclusively license patents and patent applications in our portfolio relating to neffy that are pending at the patent offices in the United States, Europe, Japan, and other foreign jurisdictions, however, we cannot predict: • if and when patents may issue based on the patent applications we own, co-own or exclusively license; • the scope of protection of any patent issuing based on the patent applications we own, co-own or exclusively license; • whether the claims of any patent issuing based on the patent applications we own, co-own or exclusively license will provide protection against competitors, • whether or not third parties will find ways to invalidate or circumvent our patent rights; • whether or not others will obtain patents claiming aspects similar to those covered by the patent applications we own, co-own or exclusively license; • whether we will need to initiate litigation or administrative proceedings to enforce and/or defend our patent rights which will be costly whether we win or lose; • whether the patent applications that we own, co-own or exclusively license will result in issued patents with claims that cover neffy or any of our future product candidates or uses thereof; and/or • whether we may experience patent office interruption or delays to our ability to timely secure patent coverage to our product candidates.
If we or any of the third parties with whom we engage were to experience renewed shutdowns or other business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively affected, which could have a material adverse impact on our business and our results of operations and financial conditions.
If we or any of the third parties with whom we engage were to experience shutdowns or other business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively affected, which could have a material adverse impact on our business and our results of operations and financial conditions.
Finally, a competitor might receive FDA approval before neffy and obtain non-patent market exclusivity, which could delay approval of neffy . We may incur unexpected costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of neffy or any future product candidates.
Finally, a competitor might receive FDA approval before neffy and obtain non-patent market exclusivity, which could delay approval of neffy . 55 We may incur unexpected costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of neffy or any future product candidates.
If any future public health crisis is not contained, we may experience disruptions that could severely impact our business and clinical trials, including: • delays or difficulties in our commercialization efforts; • delays or difficulties in enrolling patients in our clinical trials; • delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; • diversion of healthcare resources away from the conduct of clinical trials, including the diversion of sites or facilities serving as our clinical trial sites and staff supporting the conduct of our clinical trials, including our trained therapists, or absenteeism that reduces site resources; • interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal, state or national governments, employers and others or interruption of clinical trial subject visits and study procedures, the occurrence of which could affect the integrity of clinical trial data; • risk that participants enrolled in our clinical trials will acquire a virus or illness while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events or patient withdrawals from our trials; • limitations in employee resources that would otherwise be focused on conducting our clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people; • delays in receiving authorizations from regulatory authorities to initiate our future clinical trials; • delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials; • interruption in global shipping that may affect the transport of clinical trial materials, such as neffy used in our clinical trials; • changes in local regulations as part of a response to the public health crisis which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or the discontinuation of the clinical trials altogether; • interruptions or delays in nonclinical studies due to restricted or limited operations at research and development laboratory facilities; • delays in necessary interactions with local regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government employees; and • refusal of the FDA, the EMA or the other regulatory bodies to accept data from clinical trials in affected geographies outside the United States, the EU or other relevant local geographies. 86 Any negative impact a resurgence of COVID-19 or other public health crisis has on patient enrollment or treatment, or the development of neffy and any future product candidates, could cause costly delays to clinical trial activities, which could adversely affect our ability to obtain regulatory approval for and to commercialize neffy and any future product candidates, if approved, increase our operating expenses, which could have a material adverse effect on our financial results.
If any future public health crisis is not contained, we may experience disruptions that could severely impact our business and clinical trials, including: • delays or difficulties in our commercialization efforts; • delays or difficulties in enrolling patients in our clinical trials; • delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; • diversion of healthcare resources away from the conduct of clinical trials, including the diversion of sites or facilities serving as our clinical trial sites and staff supporting the conduct of our clinical trials, including our trained therapists, or absenteeism that reduces site resources; • interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal, state or national governments, employers and others or interruption of clinical trial subject visits and study procedures, the occurrence of which could affect the integrity of clinical trial data; • risk that participants enrolled in our clinical trials will acquire a virus or illness while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events or patient withdrawals from our trials; • limitations in employee resources that would otherwise be focused on conducting our clinical trials, including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people; • delays in receiving authorizations from regulatory authorities to initiate our future clinical trials; • delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials; • interruption in global shipping that may affect the transport of clinical trial materials, such as neffy used in our clinical trials; • changes in local regulations as part of a response to the public health crisis which may require us to change the ways in which our clinical trials are conducted, which may result in unexpected costs, or the discontinuation of the clinical trials altogether; • interruptions or delays in nonclinical studies due to restricted or limited operations at research and development laboratory facilities; • delays in necessary interactions with local regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government employees; and • refusal of the FDA, the EMA or the other regulatory bodies to accept data from clinical trials in affected geographies outside the United States, the EU or other relevant local geographies. 93 Any negative impact a public health crisis has on patient enrollment or treatment, or the development of neffy and any future product candidates, could cause costly delays to clinical trial activities, which could adversely affect our ability to obtain regulatory approval for and to commercialize neffy and any future product candidates, if approved, increase our operating expenses, which could have a material adverse effect on our financial results.
We do not control the individual efforts of our licensing and collaboration partners and have limited ability to terminate these agreements or have assigned assets returned to us if such licensing and collaboration partners do not perform as anticipated. 60 The failure of our licensing and collaboration partners to devote sufficient time and effort to the development and commercialization of neffy ; to meet their obligations to us, including for future royalty and milestone payments; to adequately deploy business continuity plans in the event of a crisis; to adequately respond to the adverse impact of military action, sanctions and market disruptions; and/or to satisfactorily resolve significant disagreements with us or address other factors could have an adverse impact on our financial results and operations.
We do not control the individual efforts of our licensing and collaboration partners and have limited ability to terminate these agreements or have assigned assets returned to us if such licensing and collaboration partners do not perform as anticipated. 66 The failure of our licensing and collaboration partners to devote sufficient time and effort to the development and commercialization of neffy ; to meet their obligations to us, including for future royalty and milestone payments; to adequately deploy business continuity plans in the event of a crisis; to adequately respond to the adverse impact of military action, sanctions and market disruptions; and/or to satisfactorily resolve significant disagreements with us or address other factors could have an adverse impact on our financial results and operations.
Other global health concerns could also result in social, economic, and labor instability in the countries in which we or the third parties with whom we engage operate. 85 While we have been working closely with our third-party manufacturers, distributors and other partners to manage our supply chain activities and mitigate potential disruptions to the production of neffy as a result of pandemics, epidemics or other infectious disease outbreaks, if such a public health crisis were to persist for an extended period of time, there could be significant and material disruptions to our supply chain and operations, and associated delays in the manufacturing and supply of neffy and any future product candidates.
Other global health concerns could also result in social, economic, and labor instability in the countries in which we or the third parties with whom we engage operate. 92 While we have been working closely with our third-party manufacturers, distributors and other partners to manage our supply chain activities and mitigate potential disruptions to the production of neffy as a result of pandemics, epidemics or other infectious disease outbreaks, if such a public health crisis were to persist for an extended period of time, there could be significant and material disruptions to our supply chain and operations, and associated delays in the manufacturing and supply of neffy and any future product candidates.
A security incident or other interruption could disrupt our ability (and that of third parties upon whom we rely) to provide our services. We may expend significant resources or modify our business activities (including clinical trials) to try to protect against security incidents.
A security incident or other interruption could disrupt our ability (and that of third parties upon whom we rely) to provide our services. 79 We may expend significant resources or modify our business activities (including clinical trials) to try to protect against security incidents.
These third parties compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites, as well as in acquiring technologies complementary to, or necessary for, our activities. 53 If the FDA, the EMA or other comparable foreign regulatory authorities approve generic versions of neffy or any future product candidate of ours that receives regulatory approval, or such authorities do not grant our products appropriate periods of non-patent exclusivity before approving generic versions of such products, the sales of such products could be adversely affected.
These third parties compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites, as well as in acquiring technologies complementary to, or necessary for, our activities. 60 If the FDA, the EMA or other comparable foreign regulatory authorities approve generic versions of neffy or any future product candidate of ours that receives regulatory approval, or such authorities do not grant our products appropriate periods of non-patent exclusivity before approving generic versions of such products, the sales of such products could be adversely affected.
Unused federal NOLs generated in tax years beginning after December 31, 2017, will not expire and may be carried forward indefinitely, but the deductibility of such federal NOL carryforwards in taxable years beginning after December 31, 2020, is limited to 80% of taxable income.
Unused federal NOLs generated in tax years beginning after December 31, 2017, will not expire and may be carried forward indefinitely, but the deductibility of such federal NOL carryforwards is limited to 80% of taxable income.
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our research and development of, and seek regulatory approvals and prepare for commercialization for our product candidate, neffy , an investigational, new formulation of epinephrine, for the emergency treatment of Type I allergic reactions and potential additional indications. 40 We anticipate that our expenses will increase substantially if and as we: • continue to develop and conduct nonclinical studies and clinical trials for neffy for the emergency treatment of Type I allergic reactions and potential additional indications; • seek regulatory approvals in the United States, the EU and other geographic regions for neffy for the emergency treatment of Type I allergic reactions and other indications that successfully complete clinical development; • seek to identify additional product candidates; • initiate and continue research, preclinical and clinical development efforts for any future product candidates; • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, negative or mixed clinical trial results, safety issues or other regulatory challenges, the risk of which in each case may be exacerbated by COVID-19 or other health epidemic or pandemic; • add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product candidate development and potential future commercialization efforts and help us comply with our obligations as a public company; • maintain, expand and protect our intellectual property portfolio; • establish or expand our sales, marketing, distribution, manufacturing, supply chain and other commercial infrastructure in the future to commercialize any products for which we may obtain regulatory approval; and • acquire or in-license other product candidates and technologies.
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our research and development of, and seek regulatory approvals and prepare for commercialization for our product candidate, neffy , an investigational, new formulation of epinephrine, for the emergency treatment of Type I allergic reactions and potential additional indications. 46 We anticipate that our expenses will increase substantially if and as we: • continue to develop and conduct nonclinical studies and clinical trials for neffy for the emergency treatment of Type I allergic reactions and potential additional indications; • seek regulatory approvals in the United States, the EU and other geographic regions for neffy for the emergency treatment of Type I allergic reactions and other indications that successfully complete clinical development; • seek to identify additional product candidates; • initiate and continue research, preclinical and clinical development efforts for any future product candidates; • experience any delays or encounter any issues with any of the above, including but not limited to failed studies, negative or mixed clinical trial results, safety issues or other regulatory challenges, the risk of which in each case may be exacerbated by a health epidemic or pandemic; • add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product candidate development and potential future commercialization efforts and help us comply with our obligations as a public company; • maintain, expand and protect our intellectual property portfolio; • establish or expand our sales, marketing, distribution, manufacturing, supply chain and other commercial infrastructure in the future to commercialize any products for which we may obtain regulatory approval; and • acquire or in-license other product candidates and technologies.
These broad market fluctuations may also adversely affect the trading price of our common stock. In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies.
These broad market fluctuations may also adversely affect the trading price of our common stock. 96 In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies.
Any termination of collaborations we enter into in the future, or any delay in entering into collaborations related to neffy or any future product candidate, could delay the development and commercialization of neffy or any future product candidate and reduce their competitiveness if they reach the market, which could have a material adverse effect on our business, financial condition and results of operations. 61 Our reliance on third parties requires us to share our trade secrets, know-how and other proprietary information, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.
Any termination of collaborations we enter into in the future, or any delay in entering into collaborations related to neffy or any future product candidate, could delay the development and commercialization of neffy or any future product candidate and reduce their competitiveness if they reach the market, which could have a material adverse effect on our business, financial condition and results of operations. 67 Our reliance on third parties requires us to share our trade secrets, know-how and other proprietary information, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.
Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations. 69 Our relationships with customers, health care professionals and third-party payors may be subject to applicable healthcare laws, which could expose us to penalties, including administrative, civil or criminal penalties, damages, fines, imprisonment, exclusion from participation in federal healthcare programs such as Medicare and Medicaid, reputational harm, the curtailment or restructuring of our operations and diminished future profits and earnings.
Ongoing healthcare legislative and regulatory reform measures may have a material adverse effect on our business and results of operations. 75 Our relationships with customers, health care professionals and third-party payors may be subject to applicable healthcare laws, which could expose us to penalties, including administrative, civil or criminal penalties, damages, fines, imprisonment, exclusion from participation in federal healthcare programs such as Medicare and Medicaid, reputational harm, the curtailment or restructuring of our operations and diminished future profits and earnings.
The existence of these provisions could negatively affect the price of our common stock and limit opportunities for our stockholders to realize value in a corporate transaction. 91 Our amended and restated certificate of incorporation designates the state courts the State of Delaware or, if no state court located within the State of Delaware has jurisdiction, the federal court for the District of Delaware, and the federal district courts of the United States of America to be the exclusive forums for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers and employees.
The existence of these provisions could negatively affect the price of our common stock and limit opportunities for our stockholders to realize value in a corporate transaction. 98 Our amended and restated certificate of incorporation designates the state courts of the State of Delaware or, if no state court located within the State of Delaware has jurisdiction, the federal court for the District of Delaware, and the federal district courts of the United States of America to be the exclusive forums for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers and employees.
We cannot assure you that it will be able to hire and/or retain adequate staffing levels to develop neffy or to run our operations and/or to accomplish all of the objectives that we otherwise would seek to accomplish. 87 Our employees, independent contractors, consultants, current and future licensing and collaboration partners and CROs may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.
We cannot assure you that it will be able to hire and/or retain adequate staffing levels to develop neffy or to run our operations and/or to accomplish all of the objectives that we otherwise would seek to accomplish. 94 Our employees, independent contractors, consultants, current and future licensing and collaboration partners and CROs may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation.
Thus, we and any current and future licensing and collaboration partners will not be able to promote any products we develop for indications or uses for which they are not approved. 64 In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA, EMA and other foreign regulatory requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs, which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements.
Thus, we and any current and future licensing and collaboration partners will not be able to promote any products we develop for indications or uses for which they are not approved. 70 In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA, EMA and other foreign regulatory requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs, which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements.
Any disclosure, either intentional or unintentional, by our employees, the employees of third parties with whom we share our facilities or third-party consultants and vendors that we engage to perform research, clinical trials or manufacturing activities, or misappropriation by third parties (such as through a cybersecurity breach) of our trade secrets or proprietary information could enable competitors to duplicate or surpass our technological achievements, thus eroding our competitive position in our market. 83 Trade secrets and unpatented know-how can be difficult to protect.
Any disclosure, either intentional or unintentional, by our employees, the employees of third parties with whom we share our facilities or third-party consultants and vendors that we engage to perform research, clinical trials or manufacturing activities, or misappropriation by third parties (such as through a cybersecurity breach) of our trade secrets or proprietary information could enable competitors to duplicate or surpass our technological achievements, thus eroding our competitive position in our market. 90 Trade secrets and unpatented know-how can be difficult to protect.
If we fail to comply with the regulatory requirements in international markets and/or obtain and maintain applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of neffy or any future product candidates will be harmed. 54 We received Fast Track designation for neffy in the United States and may in the future pursue Fast Track designation for other product candidates that we may develop, but we might not receive such future designations, and Fast Track designations may not lead to a faster development or regulatory review or approval process.
If we fail to comply with the regulatory requirements in international markets and/or obtain and maintain applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of neffy or any future product candidates will be harmed. 61 We received Fast Track designation for neffy in the United States and may in the future pursue Fast Track designation for other product candidates that we may develop, but we might not receive such future designations, and Fast Track designations may not lead to a faster development or regulatory review or approval process.
Even if regulatory approval of a product candidate is granted, the approval may be subject to limitations on the indications or uses for which the product may be marketed or to the conditions of approval, including the requirement in the United States to implement a Risk Evaluation and Mitigation Strategy or the inclusion of a Boxed Warning, which highlights a specific life-threatening safety risk. 63 The FDA, the EMA and other regulatory authorities may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of a product.
Even if regulatory approval of a product candidate is granted, the approval may be subject to limitations on the indications or uses for which the product may be marketed or to the conditions of approval, including the requirement in the United States to implement a Risk Evaluation and Mitigation Strategy or the inclusion of a Boxed Warning, which highlights a specific life-threatening safety risk. 69 The FDA, the EMA and other regulatory authorities may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of a product.
We cannot guarantee that any of our patent searches or analyses, including the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third-party patent and pending application in the United States and abroad that is relevant to our operations or necessary for the commercialization of our product candidates in any jurisdiction. 78 Numerous U.S. and foreign patents and pending patent applications exist in our market that are owned by third parties.
We cannot guarantee that any of our patent searches or analyses, including the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third-party patent and pending application in the United States and abroad that is relevant to our operations or necessary for the commercialization of our product candidates in any jurisdiction. 85 Numerous U.S. and foreign patents and pending patent applications exist in our market that are owned by third parties.
As a result, it may be more difficult for us to attract and retain qualified individuals to serve on our board of directors or as our executive officers, which may adversely affect investor confidence in us and could cause our business or stock price to suffer. 90 Delaware law and provisions in our amended and restated certificate of incorporation and amended and restated bylaws could make a merger, tender offer or proxy contest difficult, thereby depressing the trading price of our common stock.
As a result, it may be more difficult for us to attract and retain qualified individuals to serve on our board of directors or as our executive officers, which may adversely affect investor confidence in us and could cause our business or stock price to suffer. 97 Delaware law and provisions in our amended and restated certificate of incorporation and amended and restated bylaws could make a merger, tender offer or proxy contest difficult, thereby depressing the trading price of our common stock.
This may make an investment in our company riskier than similar companies that have multiple product candidates in active development that may be able to better sustain failure of a lead product candidate. 43 We currently have no products approved for marketing and are investing the majority of our efforts and financial resources in the development of our sole product candidate, neffy , for the emergency treatment of Type I allergic reactions and potential other indications.
This may make an investment in our company riskier than similar companies that have multiple product candidates in active development that may be able to better sustain failure of a lead product candidate. 50 We currently have no products approved for marketing and are investing the majority of our efforts and financial resources in the development of our sole product candidate, neffy , for the emergency treatment of Type I allergic reactions and potential other indications.
Unless and until we can secure an alternative source for drug product manufacturing and final packaging, our dependence on Renaissance will subject us to the possible risks of shortages, interruptions and price fluctuations if neffy is approved for commercialization. 58 We may be unable to maintain or establish required agreements with third-party manufacturers or to do so on acceptable terms.
Unless and until we can secure an alternative source for drug product manufacturing and final packaging, our dependence on Renaissance will subject us to the possible risks of shortages, interruptions and price fluctuations if neffy is approved for commercialization. 64 We may be unable to maintain or establish required agreements with third-party manufacturers or to do so on acceptable terms.
These laws and the regulations and policies implementing them, as well as other healthcare reform measures that may be adopted in the future, may have a material adverse effect on our industry generally and on our ability to successfully develop and commercialize neffy or any future product candidates. 67 Governments outside the United States may impose strict price controls, which may adversely affect our revenues, if any.
These laws and the regulations and policies implementing them, as well as other healthcare reform measures that may be adopted in the future, may have a material adverse effect on our industry generally and on our ability to successfully develop and commercialize neffy or any future product candidates. 73 Governments outside the United States may impose strict price controls, which may adversely affect our revenues, if any.
In addition, any revenue we receive will depend in whole or in part upon the efforts of these third parties, which may not be successful and are generally not within our control. 62 We also compete with many companies that currently have extensive, experienced and well-funded sales, distribution and marketing operations to recruit, hire, train and retain marketing and sales personnel.
In addition, any revenue we receive will depend in whole or in part upon the efforts of these third parties, which may not be successful and are generally not within our control. 68 We also compete with many companies that currently have extensive, experienced and well-funded sales, distribution and marketing operations to recruit, hire, train and retain marketing and sales personnel.
While we believe that we will have the necessary supporting data to submit a marketing application under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (“Section 505(b)(2)”) regulatory pathway to the FDA for neffy for the emergency treatment of Type I allergic reactions for adults and children greater than 30 kg in weight, and upon completion of our ongoing pediatric study, EPI-10, for children between 15 and 30 kg in weight, there can be no assurance that the FDA will agree that the Section 505(b)(2) pathway is appropriate or will approve any such application or any future application for additional indication or future product candidates.
While we believe that we will have the necessary supporting data to submit a marketing application under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (“Section 505(b)(2)”) regulatory pathway to the FDA for neffy for the emergency treatment of Type I allergic reactions upon completion of our ongoing pediatric study, EPI-10, for children between 15 and 30 kg in weight, there can be no assurance that the FDA will agree that the Section 505(b)(2) pathway is appropriate or will approve any such application or any future application for additional indication or future product candidates.
If any of these events were to occur or we otherwise fail to comply with applicable regulations, we could incur liability, face regulatory actions or incur other harm to our business. 51 If we fail to develop and commercialize neffy for additional indications or fail to discover, develop and commercialize other product candidates, we may be unable to grow our business and our ability to achieve our strategic objectives would be impaired.
If any of these events were to occur or we otherwise fail to comply with applicable regulations, we could incur liability, face regulatory actions or incur other harm to our business. 58 If we fail to develop and commercialize neffy for additional indications or fail to discover, develop and commercialize other product candidates, we may be unable to grow our business and our ability to achieve our strategic objectives would be impaired.
Even if neffy is approved for the emergency treatment of Type I allergic reactions, there remains significant uncertainty as to whether neffy will be successfully developed and ultimately approved for any other indication we are exploring or pursuing. As part of our longer-term growth strategy, we plan to evaluate and potentially develop neffy for other indications.
Even if neffy is approved for the emergency treatment of Type I allergic reactions, there remains significant uncertainty as to whether neffy will be successfully developed and ultimately approved for any other indication we are exploring or pursuing. As part of our longer-term growth strategy, we plan to evaluate and potentially develop neffy for other indications, including urticaria.
Any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history or a history of successfully developing and commercializing pharmaceutical products. 41 We may encounter unforeseen expenses, difficulties, complications, delays and other known or unknown factors in achieving our business objectives.
Any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history or a history of successfully developing and commercializing pharmaceutical products. 47 We may encounter unforeseen expenses, difficulties, complications, delays and other known or unknown factors in achieving our business objectives.
Our current and anticipated future dependence upon others for the manufacture of neffy or any future product candidates or drugs may adversely affect our future profit margins and our ability to commercialize neffy or any future product candidate that receives marketing approval on a timely and competitive basis. 59 We rely on third parties to conduct our nonclinical studies and clinical trials.
Our current and anticipated future dependence upon others for the manufacture of neffy or any future product candidates or drugs may adversely affect our future profit margins and our ability to commercialize neffy or any future product candidate that receives marketing approval on a timely and competitive basis. 65 We rely on third parties to conduct our nonclinical studies and clinical trials.
These changes include aggregate reductions to Medicare payments to providers of up to two percent per fiscal year pursuant to the Budget Control Act of 2011, which went into effect on April 1, 2013, and due to subsequent legislative amendments, will remain in effect until 2031, unless additional Congressional action is taken.
These changes include aggregate reductions to Medicare payments to providers of up to two percent per fiscal year pursuant to the Budget Control Act of 2011, which went into effect on April 1, 2013, and due to subsequent legislative amendments, will remain in effect until 2032, unless additional Congressional action is taken.
Any of these occurrences could have a material adverse effect on our business, financial condition, results of operations, cash flows and prospects. 80 Competitors may infringe our patents, trademarks, copyrights or other intellectual property that relate to our research programs and product candidates, their respective methods of use, manufacture and formulations thereof.
Any of these occurrences could have a material adverse effect on our business, financial condition, results of operations, cash flows and prospects. 87 Competitors may infringe our patents, trademarks, copyrights or other intellectual property that relate to our research programs and product candidates, their respective methods of use, manufacture and formulations thereof.
The inability to obtain any third-party license required to develop or commercialize any of our product candidates could cause us to abandon any related efforts, which could seriously harm our business and operations. 84 Any collaboration arrangements that we may enter into in the future may not be successful, which could adversely affect our ability to develop and commercialize our products.
The inability to obtain any third-party license required to develop or commercialize any of our product candidates could cause us to abandon any related efforts, which could seriously harm our business and operations. 91 Any collaboration arrangements that we may enter into in the future may not be successful, which could adversely affect our ability to develop and commercialize our products.
If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize or obtain a satisfactory financial return on neffy or any future product candidates that we may develop. 68 There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products.
If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize or obtain a satisfactory financial return on neffy or any future product candidates that we may develop. 74 There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products.
Though these license agreements may provide guidelines for how our trademarks and trade names may be used, a breach of these agreements or misuse of our trademarks and trade names by our licensees may jeopardize our rights in or diminish the goodwill associated with our trademarks and trade names. 82 Intellectual property rights do not necessarily address all potential threats to our competitive advantage.
Though these license agreements may provide guidelines for how our trademarks and trade names may be used, a breach of these agreements or misuse of our trademarks and trade names by our licensees may jeopardize our rights in or diminish the goodwill associated with our trademarks and trade names. 89 Intellectual property rights do not necessarily address all potential threats to our competitive advantage.
In addition, we may not have sufficient resources to bring these actions to a successful conclusion. 79 If we are found to infringe a third party’s intellectual property rights, we could be forced, including by court order, to cease developing, manufacturing or commercializing the infringing product candidate or product.
In addition, we may not have sufficient resources to bring these actions to a successful conclusion. 86 If we are found to infringe a third party’s intellectual property rights, we could be forced, including by court order, to cease developing, manufacturing or commercializing the infringing product candidate or product.
If the equity and credit markets deteriorate, it may make any necessary debt or equity financing more difficult, more costly or more dilutive. 42 We believe that our existing cash and cash equivalents will be sufficient to fund our planned operations for at least three years.
If the equity and credit markets deteriorate, it may make any necessary debt or equity financing more difficult, more costly or more dilutive. 48 We believe that our existing cash and cash equivalents will be sufficient to fund our planned operations for at least three years.
Without patent protection, we may be open to competition from generic versions of neffy . 77 We cannot ensure that patent rights relating to inventions described and claimed in our pending patent applications will issue or that patents based on our patent applications will not be challenged and rendered invalid and/or unenforceable.
Without patent protection, we may be open to competition from generic versions of neffy . 84 We cannot ensure that patent rights relating to inventions described and claimed in our pending patent applications will issue or that patents based on our patent applications will not be challenged and rendered invalid and/or unenforceable.
We are not able to predict the effect that sales may have on the prevailing market price of our common stock. 92 If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business or our market, our stock price and trading volume could decline.
We are not able to predict the effect that sales may have on the prevailing market price of our common stock. 99 If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business or our market, our stock price and trading volume could decline.
In such cases, we may decide that the more prudent course of action is to simply monitor the situation or initiate or seek some other non-litigious action or solution. 81 Intellectual property litigation may lead to unfavorable publicity that harms our reputation.
In such cases, we may decide that the more prudent course of action is to simply monitor the situation or initiate or seek some other non-litigious action or solution. 88 Intellectual property litigation may lead to unfavorable publicity that harms our reputation.
Accordingly, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected. Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents.
Accordingly, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected. 82 Patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents.
COVID-19 also caused significant volatility in public equity markets and disruptions to the United States and global economies and any future pandemic, epidemic, infectious disease outbreak or similar public health crisis could lead to further market dislocation. Any such increased volatility and economic dislocation may make it more difficult for us to raise capital on favorable terms, or at all.
COVID-19 caused significant volatility in public equity markets and disruptions to the United States and global economies and any future pandemic, epidemic, infectious disease outbreak or similar public health crisis could lead to market dislocation. Any such volatility and economic dislocation may make it more difficult for us to raise capital on favorable terms, or at all.
Even if we established infringement by competitors, a court may decide not to grant an injunction against further infringing activity by competitors and instead award only monetary damages, which may or may not be an adequate remedy.
Even if we establish infringement by competitors, a court may decide not to grant an injunction against further infringing activity by competitors and instead award only monetary damages, which may or may not be an adequate remedy.
Factors that may inhibit our efforts to commercialize neffy or any future product candidate on its own include: • our inability to recruit and retain adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to or persuade adequate numbers of allergists, pediatricians and other physicians to prescribe any future products; • 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; • the availability of adequate coverage by and reimbursement from third-party payors; and • unforeseen costs and expenses associated with building out an independent sales and marketing organization.
Factors that may inhibit our efforts to commercialize neffy or any future product candidate on its own include: • our inability to recruit and retain adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to or our failure to educate adequate numbers of allergists, pediatricians and other physicians on the benefits of our future products; • 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; • the availability of adequate coverage by and reimbursement from third-party payors; and • unforeseen costs and expenses associated with building out an independent sales and marketing organization.
Even if neffy is approved for the emergency treatment of Type I allergic reactions, there will remain significant uncertainty regarding whether neffy will be successfully developed or approved for any other indication.
Even if neffy is approved for the emergency treatment of Type I allergic reactions, there will remain significant uncertainty regarding whether neffy will be successfully developed or approved for any other indication, including urticaria.
Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time and may adversely affect our anticipated future revenues and operating earnings. We rely on patent, trademark, trade secret and other intellectual property protection in the discovery, development, manufacturing and sale of our product candidates.
Patent terms may be inadequate to protect our competitive position for neffy or for any of our future product candidates for an adequate amount of time and may adversely affect our anticipated future revenues and operating earnings. We rely on patent, trademark, trade secret and other intellectual property protection in the discovery, development, manufacturing and sale of our product candidates.
There can be no guarantee we will not experience other impacts from a resurgence of COVID-19 or other pandemics, epidemics or infectious disease outbreaks, such as being forced to further delay or pause enrollment, experiencing potential interruptions to our supply chain, facing difficulties or additional costs in enrolling patients in future clinical trials or being able to achieve full enrollment of our studies within the timeframes we anticipate, or at all.
There can be no guarantee we will not experience other impacts from other pandemics, epidemics or infectious disease outbreaks, such as being forced to further delay or pause enrollment, experiencing potential interruptions to our supply chain, facing difficulties or additional costs in enrolling patients in future clinical trials or being able to achieve full enrollment of our studies within the timeframes we anticipate, or at all.
Some European regulators have ordered certain companies to suspend or permanently cease certain transfers of personal data out of Europe for allegedly violating the GDPR’s cross-border data transfer limitations. Obligations related to data privacy and security are quickly changing, becoming increasingly stringent, and creating regulatory uncertainty.
Some European regulators have ordered certain companies to suspend or permanently cease certain transfers of personal data out of Europe for allegedly violating the GDPR’s cross-border data transfer limitations. Obligations related to data privacy and security (and consumers’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty.
Our commercial success depends, in part, on our ability to develop, manufacture, market and sell our product candidates without infringing the intellectual property and other proprietary rights of third parties. Third parties may allege that we have infringed or misappropriated their intellectual property.
Our commercial success depends, in part, on our ability to develop, manufacture, market and sell neffy or any of our future product candidates without infringing the intellectual property and other proprietary rights of third parties. Third parties may allege that we have infringed or misappropriated their intellectual property.
Some of the factors that may cause the market price of our common stock to fluctuate include: • our ability to obtain regulatory approvals for our product candidates, and delays or failures to obtain such approvals; • failure of any of our product candidates, if approved, to achieve commercial success; • failure by us to maintain our existing third-party license and supply agreements; 88 • failure by us or our licensors to prosecute, maintain, or enforce our intellectual property rights; • changes in laws or regulations applicable to our product candidates; • any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices; • adverse regulatory authority decisions; • introduction of new products, services or technologies by our competitors; • failure to meet or exceed financial and development projections we may provide to the public; • failure to meet or exceed the financial and development projections of the investment community; • the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community; • announcements of significant acquisitions, strategic collaborations, joint ventures or capital commitments by us or our competitors; • disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our product candidates; • additions or departures of key personnel; • significant lawsuits, including patent or stockholder litigation; • if securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our business and stock; • changes in the market valuations of similar companies; • general market or macroeconomic conditions; • sales of our common stock by us or our stockholders in the future; • trading volume of our common stock; • announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships or capital commitments; • adverse publicity generally, including with respect to other products and potential products in such markets; • the introduction of technological innovations or new therapies that compete with potential products of ours; • changes in the structure of health care payment systems; and • period-to-period fluctuations in our financial results . 89 Moreover, the stock markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies.
Some of the factors that may cause the market price of our common stock to fluctuate include: • our ability to obtain regulatory approvals for our product candidates, and delays or failures to obtain such approvals; • failure of any of our product candidates, if approved, to achieve commercial success; • failure by us to maintain our existing third-party license and supply agreements; • failure by us or our licensors to prosecute, maintain, or enforce our intellectual property rights; • changes in laws or regulations applicable to our product candidates; • any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices; • adverse regulatory authority decisions; • introduction of new products, services or technologies by our competitors; • failure to meet or exceed financial and development projections we may provide to the public; • failure to meet or exceed the financial and development projections of the investment community; • the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community; • announcements of significant acquisitions, strategic collaborations, joint ventures or capital commitments by us or our competitors; • disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our product candidates; • additions or departures of key personnel; • significant lawsuits, including patent or stockholder litigation; • if securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our business and stock; • changes in the market valuations of similar companies; • general market or macroeconomic conditions; • sales of our common stock by us or our stockholders in the future; • trading volume of our common stock; • announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships or capital commitments; • adverse publicity generally, including with respect to other products and potential products in such markets; • the introduction of technological innovations or new therapies that compete with potential products of ours; • changes in the structure of health care payment systems; and • period-to-period fluctuations in our financial results.
To the extent a resurgence of COVID-19 or any future pandemic, epidemic, infectious disease outbreak or other public health crisis adversely affects our business and financial results, it may also heighten many of the other risks described in this “Risk Factors” section, such as those relating to the timing and completion of our clinical trials and our ability to obtain future financing.
To the extent a future pandemic, epidemic, infectious disease outbreak or other public health crisis adversely affects our business and financial results, it may also heighten many of the other risks described in this “Risk Factors” section, such as those relating to the timing and completion of our clinical trials and our ability to obtain future financing.
Security incidents and attendant consequences may cause customers to stop using our services, deter new customers from using our services, and negatively impact our ability to grow and operate our business.
Security incidents and attendant consequences may prevent or cause customers to stop using our services, deter new customers from using our services, and negatively impact our ability to grow and operate our business.
The Leahy-Smith Act also includes a number of significant changes that affect the way patent applications will be prosecuted and also may affect patent litigation.
The Leahy-Smith Act also included a number of significant changes that affect the way patent applications will be prosecuted and also may affect patent litigation.
There is a substantial amount of intellectual property litigation in the pharmaceutical industry, and we may become party to, or threatened with, litigation or other adversarial proceedings regarding intellectual property rights with respect to our products candidates. Third parties may assert infringement claims against us based on existing or future intellectual property rights.
There is a substantial amount of intellectual property litigation in the pharmaceutical industry, and we may become party to, or threatened with, litigation or other adversarial proceedings regarding intellectual property rights with respect to neffy or any of our future product candidates. Third parties may assert infringement claims against us based on existing or future intellectual property rights.
If we are sued for infringing intellectual property rights of third parties, such litigation could be costly and time consuming and could prevent or delay us from developing or commercializing our product candidates.
If we are sued for infringing intellectual property rights of third parties, such litigation could be costly and time consuming and could prevent or delay us from developing or commercializing neffy or any of our future product candidates.
If we are unable to obtain or maintain patent protection with respect to our product candidates, and their uses, our business, financial condition, results of operations and prospects could be materially harmed.
If we are unable to obtain or maintain patent protection with respect to neffy or any of our future product candidates, and their uses, our business, financial condition, results of operations and prospects could be materially harmed.
If we or the third parties on which we rely fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to: government enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar); litigation (including class-action claims); additional reporting requirements and/or oversight; bans on processing personal data; and orders to destroy or not use personal data.
If we or the third parties on which we rely fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to: government enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar); litigation (including class-action claims) and mass arbitration demands; additional reporting requirements and/or oversight; bans on processing personal data; orders to destroy or not use personal data; and imprisonment of company officials.
Similarly, if we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable, or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case, we could ultimately be forced to cease use of such trademarks.
Similarly, if we assert trademark infringement claims, a court may determine that the marks we have asserted are unenforceable, or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case, we could ultimately be forced to cease use of such trademarks and pay for damages.
Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate, which may have an adverse effect on our ability to successfully commercialize our product candidates in all of our expected significant foreign markets.
Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate, which may have an adverse effect on our ability to successfully commercialize neffy or any of our future product candidates in all of our expected significant foreign markets.
We generally seek to protect our proprietary position by filing or in-licensing patents or patent applications in the United States and abroad related to our product candidates that are important to our business, as appropriate.
We generally seek to protect our proprietary position by filing or in-licensing patents or patent applications in the United States and abroad related to neffy or any of our future product candidates that are important to our business, as appropriate.
Risks Related to the Securities Markets and Ownership of Our Common Stock The market price of our common stock could be volatile. The market price of our common stock could be subject to significant fluctuations. Market prices for securities of pre-commercial pharmaceutical, biotechnology and other life sciences companies have historically been particularly volatile.
The market price of our common stock could be subject to significant fluctuations. Market prices for securities of pre-commercial pharmaceutical, biotechnology and other life sciences companies have historically been particularly volatile.
The Merger resulted in an ownership change of our company. The NOL carryforwards of pre-Merger, privately-held ARS Pharmaceuticals, Inc. (“ARS Pharma”) may also be subject to limitation as a result of prior shifts in equity ownership and/or the Merger. Additional ownership changes in the future could result in additional limitations on our NOL carryforwards.
The Merger resulted in an ownership change of our company. The NOL carryforwards of pre-Merger, privately-held ARS Pharma may also be subject to limitation as a result of prior shifts in equity ownership and/or the Merger. Additional ownership changes in the future could result in additional limitations on our NOL carryforwards.
For example, the FDA has indicated that the ongoing pediatric clinical trial, EPI-10, would be sufficient to support a submission of our NDA for pediatric approval of a 2.0 mg dose of neffy for children weighing more than 30 kg, and to support a separate submission for pediatric approval of a 1mg dose of ne ffy for children weighing between 15 and 30 kg; however, the FDA has not reviewed our complete clinical data, to date, and therefore there is no guarantee that the FDA will determine that the NDA currently under review by the FDA for approval of a 2.0 mg dose of neffy for children weighing more than 30 kg or any future NDA is sufficient for issuing a marketing approval of neffy for the emergency treatment of Type I allergic reactions in children.
For example, the FDA has indicated that the ongoing pediatric clinical trial, EPI-10, would be sufficient to support a submission of our NDA for pediatric approval of a 2.0 mg dose of neffy for children weighing more than 30 kg, and to support a separate submission for pediatric approval of a 1.0 mg dose of neffy for children weighing between 15 and 30 kg; however, the FDA has not reviewed our complete clinical data, to date, and therefore there is no guarantee that the FDA will determine that any future NDA is sufficient for issuing a marketing approval of neffy for the emergency treatment of Type I allergic reactions in children.
If we are unable to continue to attract and retain highly qualified personnel, our ability to develop and commercialize neffy or any future product candidates will be limited. We only have a limited number of employees to manage and operate our business. As of December 31, 2022, we had seventeen full-time employees and three part-time employees.
If we are unable to continue to attract and retain highly qualified personnel, our ability to develop and commercialize neffy or any future product candidates will be limited. We only have a limited number of employees to manage and operate our business. As of December 31, 2023, we had 24 full-time employees and 2 part-time employees.
Further, geo-political actions in the United States and in foreign countries could increase the uncertainties and costs surrounding the prosecution or maintenance of our patent applications or those of any current or future licensors and the maintenance, enforcement or defense of our issued patents or those of any current or future licensors.
Further, geo-political actions in the United States and in foreign countries (such as the Russia and Ukraine conflict) could increase the uncertainties and costs surrounding the prosecution or maintenance of our patent applications or those of any current or future licensors and the maintenance, enforcement or defense of our issued patents or those of any current or future licensors.
We cannot be certain that the claims in our pending patent applications directed to our product candidates will be considered patentable by the USPTO or by patent offices in foreign countries.
We cannot be certain that the claims in our pending patent applications directed to neffy or any of our future product candidates will be considered patentable by the USPTO or by patent offices in foreign countries.
Future sales of shares by existing stockholders could cause our stock price to decline. If our existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market after any applicable legal restrictions on resale lapse, the trading price of our common stock could decline.
If our existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market after any applicable legal restrictions on resale lapse, the trading price of our common stock could decline.
These vulnerabilities pose material risks to our business. Further, we may experience delays in developing and deploying remedial measures designed to address any such identified vulnerabilities. Applicable data privacy and security obligations may require us to notify relevant stakeholders of security incidents.
Unremediated critical or high risk vulnerabilities pose material risks to our business. Further, we may experience delays in developing and deploying remedial measures designed to address any such identified vulnerabilities. Applicable data privacy and security obligations may require us to notify relevant stakeholders of security incidents.
Further, the ACA imposed a significant annual fee on companies that manufacture or import branded prescription drug products, increased the number of entities eligible for discounts under the 340B program and included a discount on brand name drugs for Medicare Part D beneficiaries in the coverage gap, or “donut hole.” Substantial provisions affecting compliance have also been enacted, which may require us to modify our business practices with healthcare practitioners. 66 Since its enactment, there have been judicial, executive and Congressional challenges to certain aspects of the ACA.
Further, the ACA imposed a significant annual fee on companies that manufacture or import branded prescription drug products, increased the number of entities eligible for discounts under the 340B program and included a discount on brand name drugs for Medicare Part D beneficiaries in the coverage gap, or “donut hole.” Substantial provisions affecting compliance have also been enacted, which may require us to modify our business practices with healthcare practitioners.
The degree of market acceptance of neffy and any future product candidates, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and safety of the product; • the potential advantages of the product compared to competitive therapies and our ability to successfully publicize these advantages or highlight them in any marketing materials; • the prevalence and severity of any side effects; • our ability, or the ability of any current or future licensing or collaboration partners, to offer the product for sale at competitive prices; • the product’s convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try, and of physicians to prescribe, the product; • limitations or warnings, including distribution or use restrictions contained in the product’s approved labeling; • the strength of sales, marketing and distribution support; • changes in the standard of care for the targeted indications for the product; and • availability and adequacy of coverage and reimbursement from government payors, managed care plans and other third-party payors.
The degree of market acceptance of neffy and any future product candidates, if approved for commercial sale, will depend on a number of factors, including: • the efficacy and safety of the product; • the potential advantages of the product compared to competitive therapies and our ability to successfully publicize these advantages or highlight them in any marketing materials; • the prevalence and severity of any side effects; • our ability, or the ability of any current or future licensing or collaboration partners, to offer the product for sale at competitive prices; • the product’s convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try, and of physicians to prescribe, the product; • limitations or warnings, including distribution or use restrictions contained in the product’s approved labeling; • the strength of sales, marketing and distribution support; • changes in the standard of care for the targeted indications for the product; and • availability and adequacy of coverage and reimbursement from government payors, managed care plans and other third-party payors. 71 Any failure by neffy or any future product candidate of ours that obtains regulatory approval to achieve market acceptance or commercial success would adversely affect our business prospects.
COVID-19 affected and a resurgence of COVID-19 or other public health crisis may in the future affect employees of third-party CROs located in affected geographies that we rely upon to carry out our clinical trials.
COVID-19 affected and other public health crises may in the future affect employees of third-party CROs located in affected geographies that we rely upon to carry out our clinical trials.
Such a loss of patent protection could have a material adverse impact on our business, financial condition, results of operations, cash flows and prospects. We are currently a party to an inter partes review of U.S.
Such a loss of patent protection could have a material adverse impact on our business, financial condition, results of operations, cash flows and prospects. We are currently a party to an appeal from a Final Written Decision in an Inter Partes Review of U.S.
Although we enter into non-disclosure and confidentiality agreements with parties who have access to patentable aspects of our research and development output, such as our employees, corporate collaborators, outside scientific collaborators, CROs, contract manufacturers, consultants, independent contractors, advisors and other third parties, any of these parties may breach these agreements and disclose such results before a patent application is filed, thereby jeopardizing our ability to seek adequate patent protection.
It is also possible that we will fail to identify patentable aspects of our research and development results before it is too late to obtain patent protection. 80 Although we enter into non-disclosure and confidentiality agreements with parties who have access to patentable aspects of our research and development output, such as our employees, corporate collaborators, outside scientific collaborators, CROs, contract manufacturers, consultants, independent contractors, advisors and other third parties, any of these parties may breach these agreements and disclose such results before a patent application is filed, thereby jeopardizing our ability to seek adequate patent protection.

… 148 more changes not shown on this page.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

1 edited+0 added−0 removed0 unchanged
Biggest changeItem 3. Legal Proceedings. From time to time, we may be involved in various claims and legal proceedings relating to claims arising out of our operations. See Note 7- Commitments and Contingencies of this Annual Report, which is incorporated by reference in this Item 3, for any required disclosure. Item 4. Mine Safety Disclosures. Not applicable. 94 PART II
Biggest changeItem 3. Legal Proceedings. From time to time, we may be involved in various claims and legal proceedings relating to claims arising out of our operations. See Note 7 - Commitments and Contingencies of this Annual Report, which is incorporated by reference in this Item 3, for any required disclosure. Item 4. Mine Safety Disclosures. Not applicable. 102 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

7 edited+0 added−1 removed6 unchanged
Biggest changeThrough December 31, 2022, approximately $95.7 million of the net proceeds from the IPO have been used, of which, (i) an estimated $51.7 million was used toward development of Silverback’s product candidates, (ii) $0.8 million was used to repay outstanding indebtedness, (iii) $16.0 million was used for transaction costs related to the Merger, including $7.0 million in severance and change in control benefit payments made to Silverback’s former officers and (iv) an estimated $27.2 million was used for working capital and general corporate purposes.
Biggest changeThrough December 31, 2023, approximately $161.6 million of the net proceeds from the IPO have been used, of which, (i) an estimated $51.7 million was used toward development of Silverback’s product candidates, (ii) $0.8 million was used to repay outstanding indebtedness, (iii) $16.0 million was used for transaction costs related to the Merger, including $7.0 million in severance and change in control benefit payments made to Silverback’s former officers, (iv) an estimated $47.0 million was used for the development and pre-commercial launch activities related to neffy , and (v) an estimated $46.0 million was used for working capital and general corporate purposes. 103 There have been no updates to the planned use of proceeds information from the IPO as described in our final prospectus filed with the SEC pursuant to Rule 424(b)(4) on December 4, 2020, except as otherwise disclosed in our Annual Report on Form 10-K, filed with the SEC on March 31, 2022, and our Quarterly Report on Form 10-Q, filed with the SEC on August 11, 2022.
The underwriters for our initial public offering were Goldman Sachs & Co. LLC, SVB Leerink LLC, Stifel, Nicolaus & Company, Incorporated, and H.C. Wainwright & Co., LLC. On November 8, 2022, Silverback completed its reverse merger with privately-held ARS Pharmaceuticals, Inc. On November 9, 2022, the combined company changed its name to ARS Pharmaceuticals, Inc.
The underwriters for the Silverback initial public offering were Goldman Sachs & Co. LLC, SVB Leerink LLC, Stifel, Nicolaus & Company, Incorporated, and H.C. Wainwright & Co., LLC. On November 8, 2022, Silverback completed its reverse merger with privately-held ARS Pharmaceuticals, Inc. On November 9, 2022, the combined company changed its name to ARS Pharmaceuticals, Inc.
We may also use a portion of the net proceeds from the IPO to in-license, acquire or invest in complementary businesses, technologies, products or assets. However, we have no current commitments or obligations to do so. 95 Item 6. [Reserved]
We may also use a portion of the net proceeds from the IPO to license, acquire or invest in complementary businesses, technologies, products or assets. However, we have no current commitments or obligations to do so. Item 6. [Reserved]
In addition, in December 2020, the underwriters exercised their over-allotment option to purchase 1,725,000 additional shares of our common stock in the initial public offering at the public offering price of $21.00 per share, such that the aggregate offering price of the IPO was $277.7 million.
In addition, in December 2020, the underwriters exercised their over-allotment option to purchase 1,725,000 additional shares of Silverback common stock in the initial public offering at the public offering price of $21.00 per share, such that the aggregate offering price of the IPO was $277.7 million.
Use of Proceeds On December 3, 2020, we commenced our initial public offering (“IPO”) pursuant to a registration statement on Form S-1 (File No. 333-250009) that was declared effective by the SEC on December 3, 2020, for 11,500,000 shares of our common stock for sale to the public at a price of $21.00 per share.
Use of Proceeds On December 3, 2020, Silverback commenced its initial public offering (“IPO”) pursuant to a registration statement on Form S-1 (File No. 333-250009) that was declared effective by the SEC on December 3, 2020, for 11,500,000 shares of its common stock for sale to the public at a price of $21.00 per share.
The net offering proceeds to us, after deducting underwriting discounts and commissions and offering costs, were $255.3 million. No offering expenses were paid directly or indirectly to any of our directors or officers (or their associates) or persons owning 10% or more of any class of our equity securities or to any other affiliates.
The net offering proceeds to Silverback, after deducting underwriting discounts and commissions and offering costs, were $255.3 million. No offering expenses were paid directly or indirectly to any of the Silverback directors or officers (or their associates) or persons owning 10% or more of any class of Silverback’s equity securities or to any other affiliates.
Silverback’s shares of common stock were listed on the Nasdaq Global Market from December 4, 2020 through the close of business on November 8, 2022 under the ticker symbol “SBTX.” On November 9, 2022, we began trading on the Nasdaq Global Market under the ticker symbol “SPRY.” Holders of Common Stock As of March 17, 2023, there were approximately 29 holders of record of our common stock.
Silverback’s shares of common stock were listed on the Nasdaq Global Market from December 4, 2020 through the close of business on November 8, 2022 under the ticker symbol “SBTX.” On November 9, 2022, we began trading on the Nasdaq Global Market under the ticker symbol “SPRY.” Holders of Common Stock As of March 18, 2024, there were approximately 20 holders of record of our common stock.
Removed
There have been no updates to the planned use of proceeds information from the IPO as described in our final prospectus filed with the SEC pursuant to Rule 424(b)(4) on December 4, 2020, except as otherwise disclosed in our Annual Report on Form 10-K, filed with the SEC on March 31, 2022, and our Quarterly Report on Form 10-Q, filed with the SEC on August 11, 2022.

Item 7. Management's Discussion & Analysis

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

62 edited+35 added−34 removed31 unchanged
Biggest changeOur future funding requirements will depend on many factors, including: • the scope, progress, results and costs of researching and developing our current product candidates, as well as other additional product candidates we may develop and pursue in the future; • the scope and costs of manufacturing our product candidates and commercial manufacturing activities; • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates; • the number of future product candidates that we may pursue and their development requirements; • subject to receipt of regulatory approval, the costs of commercialization activities for our product candidates, to the extent such costs are not the responsibility of any collaborators, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval, revenue, if any, received from commercial sales of our product candidates or any other additional product candidates we may develop and pursue in the future; • the timing and amount of any milestone and royalty payments under the Aegis License Agreement and the Termination Agreement; • the extent to which we in-license or acquire rights to other products, product candidates or technologies; • our headcount growth and associated costs as we expand our employee headcount and establish a commercial infrastructure; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the costs of operating as a public company. 102 Until such time, if ever, as we can generate substantial product revenues to support our cost structure, we expect to finance our cash needs through a combination of our existing cash, cash equivalents, short-term investments, equity offerings, debt financings and other capital sources which may include collaborations, strategic alliances, marketing, distribution or licensing arrangements or other arrangements with third parties.
Biggest changeAdditionally, the process of testing product candidates in clinical trials is costly, and the timing of progress and expenses in these trials is uncertain. 111 Our future funding requirements will depend on many factors, including: • the scope, progress, results and costs of researching and developing our current product candidates, as well as other additional product candidates we may develop and pursue in the future; • the scope and costs of manufacturing our product candidates and commercial manufacturing activities; • the timing of, and the costs involved in, obtaining marketing approvals for our product candidates; • the number of future product candidates that we may pursue and their development requirements; • subject to receipt of regulatory approval, the costs of commercialization activities for our product candidates, to the extent such costs are not the responsibility of any collaborators, including the costs and timing of establishing product sales, marketing, distribution and manufacturing capabilities; • subject to receipt of regulatory approval, revenue, if any, received from commercial sales of our product candidates or any other additional product candidates we may develop and pursue in the future; • the timing and amount of any milestone and royalty payments under the Aegis License Agreement and the Termination Agreement; • the extent to which we in-license or acquire rights to other products, product candidates or technologies; • our headcount growth and associated costs as we expand our employee headcount and establish a commercial infrastructure; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the costs of operating as a public company.
The increase in our operating assets and liabilities was primarily due to a decrease in accounts payable and accrued liabilities of $10.3 million, an increase in prepaid and other assets of $1.2 million, and a decrease in contract liability of $1.3 million.
The decrease in our operating liabilities was primarily due to a decrease in accounts payable and accrued liabilities of $10.3 million and a decrease in contract liability of $1.3 million. The increase in our operating assets was primarily due to an increase in prepaid and other assets of $1.2 million.
In particular, we expect our cash, cash equivalents, and short-term investments will allow us to fund our expenses related to the FDA’s review of our NDA for neffy, fund proof of concept clinical trials of neffy for additional indications, fund pre-commercial manufacturing and sales and marketing activities, and if and when neffy is approved by the FDA, fund our commercial launch.
In particular, we expect our cash, cash equivalents, and short-term investments will allow us to fund our expenses related to resubmission and the FDA’s review of our NDA for neffy , fund proof of concept clinical trials of neffy for additional indications, fund pre-commercial manufacturing and sales and marketing activities, and if and when neffy is approved by the FDA, fund our commercial launch.
Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions and disruptions to and volatility in the credit and financial markets in the US, including due to recent bank failures, and worldwide resulting from macroeconomic factors.
Our ability to raise additional funds may be adversely impacted by potential worsening global economic conditions and disruptions to and volatility in the credit and financial markets in the US, including due to bank failures, and worldwide resulting from macroeconomic factors.
At the effective time of the Merger (the “Effective Time”), each share of ARS Pharma common stock outstanding immediately prior to the Effective Time, after giving effect to the automatic conversion of all shares of preferred stock of ARS Pharma into shares of ARS Pharma common stock immediately prior to the Effective Time (the “Preferred Stock Conversion”), (excluding shares held as treasury stock by ARS Pharma or held or owned by Silverback, Merger Sub or any subsidiary of Silverback or ARS Pharma and dissenting shares) were automatically converted into the right to receive shares of Silverback common stock equal to the exchange ratio of 1.1819.
At the effective time of the Merger (the “Effective Time”), each share of ARS Pharma common stock outstanding immediately prior to the Effective Time, after giving effect to the automatic conversion of all shares of preferred stock of ARS Pharma into shares of ARS Pharma common stock immediately prior to the Effective Time, (excluding shares held as treasury stock by ARS Pharma or held or owned by Silverback, Merger Sub or any subsidiary of Silverback or ARS Pharma and dissenting shares) were automatically converted into the right to receive shares of Silverback common stock equal to the exchange ratio of 1.1819.
We believe neffy ’s “no needle, no injection” approach will address a significant unmet need in the use of epinephrine, which is currently approved only in injectable formulations for the emergency treatment of Type I allergic reactions. There are approximately 25 to 40 million people in the United States who experience Type I allergic reactions.
We believe neffy ’s “no needle, no injection” approach will address a significant unmet need in the use of epinephrine, which is currently approved only in injectable formulations for the emergency treatment of Type I allergic reactions. There are approximately 40 million people in the United States who experience Type I allergic reactions.
From inception to December 31, 2022, we have raised $262.3 million in cash, cash equivalents and short-term investments, net of transaction costs, from the Merger, net proceeds of $76.3 million from the issuance of convertible preferred and common stock, $27.8 million from our collaboration, licensing, supply and distribution arrangements, and $10.0 million from bank debt.
From inception to December 31, 2023, we have raised $262.3 million in cash, cash equivalents and short-term investments, net of transaction costs, from the Merger; net proceeds of $76.3 million from the issuance of convertible preferred and common stock; $27.8 million from our collaboration, licensing, supply and distribution arrangements; and $10.0 million from bank debt.
From inception to December 31, 2022, we have raised $262.3 million in cash, cash equivalents and short-term investments, net of transaction costs, from the Merger, net proceeds of $76.3 million from the issuance of convertible preferred and common stock, $27.8 million from our collaboration, licensing, supply and distribution arrangements, and $10.0 million from bank debt.
From inception to December 31, 2023, we have raised $262.3 million in cash, cash equivalents and short-term investments, net of transaction costs, from the Merger, net proceeds of $76.3 million from the issuance of convertible preferred and common stock, $27.8 million from our collaboration, licensing, supply and distribution arrangements, and $10.0 million from bank debt.
Research and Development Expenses To date, our research and development expenses have related primarily to clinical development, process development and manufacturing costs of our product candidate.
Research and Development Expenses To date, our research and development expenses have been related primarily to clinical development, process development and manufacturing costs of our product candidate.
Of this group, approximately 16 million people have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, but only 3.3 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector with them due to the many drawbacks of these devices.
Of this group, approximately 20 million people have been diagnosed and experienced severe Type I allergic reactions that may lead to anaphylaxis, but only 3.2 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector with them due to the many drawbacks of these devices.
We have not yet commercialized any of our product candidates and we do not expect to generate revenue from sales of any product candidates until the second half of 2023 or after, if at all.
We have not yet commercialized any of our product candidates and we do not expect to generate revenue from sales of any product candidates until the second half of 2024 or after, if at all.
The preparation of these financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenue and expenses and the disclosure of contingent assets and liabilities in our financial statements.
The preparation of these financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenues and expenses and the disclosure of contingent assets and liabilities in our financial statements.
Our external research and development expenses for our clinical stage product candidate consists primarily of fees, materials and other costs paid to CROs, CMOs, consultant and contractors.
Our external research and development expenses for our clinical stage product candidate consist primarily of fees, materials and other costs paid to CROs, CMOs, consultant and contractors.
Outstanding and unexercised options and warrants to purchase shares of ARS Pharma common stock were converted into options and warrants to purchase shares of Silverback common stock. Recent Events In September 2020, we entered into a license and supply agreement (the “Recordati License and Supply Agreement”) with Recordati Ireland, Ltd (“Recordati”).
Outstanding and unexercised options and warrants to purchase shares of ARS Pharma common stock were converted into options and warrants to purchase shares of Silverback common stock. Recordati Termination Agreement In September 2020, we entered into a license and supply agreement (the “Recordati License and Supply Agreement”) with Recordati Ireland, Ltd (“Recordati”).
In addition, we cannot forecast to what degree our licensing, supply and distribution arrangements would affect our development plans and capital requirements. 98 The duration, costs and timing of clinical trials and development of our product candidates will depend on a variety of factors that include: • per patient trial costs; • the number of patients that participate in the trials; • the number of sites included in the trials; • the countries in which the trials are conducted; • the length of time required to enroll eligible patients; • the number of doses that patients receive; • the drop-out or discontinuation rates of patients; • potential additional safety monitoring or other studies requested by regulatory agencies; • the efficacy and safety profile of our product candidates, and • the cost to seek regulatory approvals for any product candidates that successfully complete clinical trials • the timing, receipt, and terms of any approvals from applicable regulatory authorities including the FDA and non-U.S. regulators; • maintaining a continued acceptable safety profile of our product candidates following approval, if any, of our product candidates; • establishing or maintaining commercial manufacturing capabilities or making arrangements with third-party manufacturers in order to ensure that we or our third-party manufacturers are able to make product successfully; • significant and changing government regulation and regulatory guidance; • the impact of any business interruptions to our operations or to those of the third parties with whom we work; and • the extent to which we establish additional strategic collaborations or other arrangements.
The duration, costs and timing of clinical trials and development of our product candidates will depend on a variety of factors that include: • per patient trial costs; • the number of patients that participate in the trials; • the number of sites included in the trials; • the countries in which the trials are conducted; • the length of time required to enroll eligible patients; • the number of doses that patients receive; • the drop-out or discontinuation rates of patients; • potential additional safety monitoring or other studies requested by regulatory agencies; • the efficacy and safety profile of our product candidates; • the cost to seek regulatory approvals for any product candidates that successfully complete clinical trials; • the timing, receipt, and terms of any approvals from applicable regulatory authorities including the FDA and non-U.S. regulators; • maintaining a continued acceptable safety profile of our product candidates following approval, if any, of our product candidates; • establishing or maintaining commercial manufacturing capabilities or making arrangements with third-party manufacturers in order to ensure that we or our third-party manufacturers are able to make product successfully; • significant and changing government regulation and regulatory guidance; • the impact of any business interruptions to our operations or to those of the third parties with whom we work; and • the extent to which we establish additional strategic collaborations or other arrangements.
We do not have any products approved for sale and have not generated any product sales. We have funded our operations primarily with proceeds from the Merger, private placement of convertible preferred stock, licensing, supply and distribution arrangements with our commercialization partners, and bank debt.
We do not have any products approved for sale and have not generated any product sales. We have funded our operations primarily with proceeds from the Merger (as more fully described below), private placement of convertible preferred stock, licensing, supply and distribution arrangements with our commercialization partners, and bank debt.
General and administrative expenses also include legal fees incurred relating to corporate and patent matters, professional fees incurred for accounting, auditing, tax and administrative consulting services, facility costs, market research costs, and insurance costs.
General and administrative expenses also include pre-commercial launch activities, legal fees incurred relating to corporate and patent matters, professional fees incurred for accounting, auditing, tax and administrative consulting services, market research costs, and insurance costs.
Pursuant to the Recordati License and Supply Agreement, we granted Recordati an exclusive, royalty-bearing, sublicensable license under our patents relating to neffy to (i) perform Recordati’s development activities on the epinephrine compositions (“Recordati Licensed Compositions”) and related products (“Recordati Licensed Products”) for commercialization in the EU, United Kingdom, and certain countries in the Middle East, Africa and Eurasia (the “Recordati Territory”), (ii) manufacture (or have manufactured) the Recordati Licensed Products for commercialization in the Recordati Territory, (iii) file and hold regulatory approvals for the Licensed Products in the Recordati Territory, and (iv) commercialize the Recordati Licensed Products in the Recordati Territory (collectively, the “Recordati Rights”). 97 On February 22, 2023, we entered into the Termination Agreement with Recordati, pursuant to which, among other things, we and Recordati agreed to terminate the Recordati License and Supply Agreement.
Pursuant to the Recordati License and Supply Agreement, we granted Recordati an exclusive, royalty-bearing, sublicensable license under our patents relating to neffy to (i) perform Recordati’s development activities on the epinephrine compositions (“Recordati Licensed Compositions”) and related products (“Recordati Licensed Products”) for commercialization in the EU, United Kingdom, and certain countries in the Middle East, Africa and Eurasia (the “Recordati Territory”), (ii) manufacture (or have manufactured) the Recordati Licensed Products for commercialization in the Recordati Territory, (iii) file and hold regulatory approvals for the Licensed Products in the Recordati Territory, and (iv) commercialize the Recordati Licensed Products in the Recordati Territory (collectively, the “Recordati Rights”).
Risk Factors.” Overview We are a biopharmaceutical company focused on the development of our novel, potentially first-in-class product candidate, neffy (previously referred to as ARS-1) for the emergency treatment of Type I allergic reactions, including anaphylaxis. neffy is a proprietary composition of epinephrine with an innovative absorption enhancer called Intravail ® , which allows neffy to provide intranasal delivery of epinephrine.
Risk Factors.” Overview We are a biopharmaceutical company focused on the development of ARS-1 (brand name neffy ), a proprietary product candidate for the needle-free intranasal delivery of epinephrine for the emergency treatment of Type I allergic reactions, including anaphylaxis. neffy is a proprietary composition of epinephrine with an innovative absorption enhancer called Intravail ® , which allows neffy to provide intranasal delivery of epinephrine.
We expect our expenses and operating losses will increase substantially as our product candidate, neffy potentially is approved by the FDA and we commence commercialization efforts, any future product candidates advance through clinical trials, we expand our clinical, regulatory, quality, manufacturing and pre-commercial sales and marketing capabilities, and incur additional costs to operate as a public company following the completion of the Merger.
We expect our expenses and operating losses will increase substantially as our product candidate, neffy potentially is approved by the FDA and we commence commercialization efforts, any future product candidates advance through clinical trials, and we expand our clinical, regulatory, quality, manufacturing and pre-commercial sales and marketing capabilities.
The increase in our operating assets and liabilities was primarily due to a decrease in contract liability of $2.5 million, partially offset by a decrease in prepaid and other assets of $1.2 million and an increase in accounts payable and accrued liabilities of $1.0 million.
The decrease in our operating liabilities was primarily due to a decrease in contract liability of $3.1 million and a decrease in accounts payable and accrued liabilities of $2.8 million. The increase in our operating assets was primarily due to an increase in prepaid and other assets of $1.4 million.
This consisted primarily of a net loss of $34.7 million and an increase in our operating assets and liabilities of $12.8 million, partially offset by non-cash charges of $7.4 million.
This consisted primarily of a net loss of $34.7 million, a decrease in our operating liabilities of $11.6 million, an increase in our operating assets of $1.2 million, partially offset by non-cash charges of $7.4 million.
The revenues for the years ended December 31, 2022 and 2021 include the recognition of revenue for the portion of upfront and clinical and regulatory milestone payments under our collaborations with Alfresa and Recordati that have been allocated to research and development services provided for during the years. Revenue under these collaboration agreements decreased $1.2 million from 2021 to 2022.
The revenues for the years ended December 31, 2023 and 2022 include the recognition of revenue for the portion of upfront and clinical and regulatory milestone payments under our collaboration agreement with Alfresa that have been allocated to research and development services provided for during these periods.
Recent Accounting Pronouncements See Note 2- Summary of Significant Accounting Policies to our consolidated financial statements for information about recent accounting pronouncements, the timing of their adoption, and our assessment, if any, of their potential impact on our financial condition and results of operations.
To date, our estimated accruals have not differed materially from actual costs incurred. Recent Accounting Pronouncements See Note 2- Summary of Significant Accounting Policies to our consolidated financial statements for information about recent accounting pronouncements, the timing of their adoption, and our assessment, if any, of their potential impact on our financial condition and results of operations.
However, the timing for regulatory approvals is outside our control, may be delayed and is uncertain. Since our inception in 2015 as ARS Pharmaceuticals, Inc., we have devoted substantially all of our efforts and financial resources to organizing and staffing our company, business planning, raising capital, performing research and development activities, and providing general and administrative support for these operations.
Since our inception in 2015 as ARS Pharmaceuticals, Inc., we have devoted substantially all of our efforts and financial resources to organizing and staffing our company, business planning, raising capital, performing research and development activities, pre-commercial activities, and providing general and administrative support for these operations.
Pursuant to the Termination Agreement, we will reacquire all of the Recordati Rights and have agreed to pay Recordati a one-time upfront payment of €3.0 million and additional payments upon achievement of certain milestones including: (i) an EMA regulatory milestone payment of €2.0 million, (ii) a milestone payment of €5.0 million upon first commercial sale of a Recordati Licensed Product in the Recordati Territory, and (iii) milestone payments of up to €5.0 million in the aggregate from sales of Recordati Licensed Product(s) in the Recordati Territory.
Pursuant to the Termination Agreement, we reacquired all of the Recordati Rights, paid Recordati a one-time upfront payment of €3.0 million, and have agreed to pay additional payments upon achievement of certain milestones including: (i) an EMA regulatory milestone payment of €2.0 million, (ii) a milestone payment of €5.0 million upon first commercial sale of a Recordati Licensed Product in the Recordati Territory, and (iii) royalty payments of up to €5.0 million in the aggregate from sales of Recordati Licensed Product(s) in the Recordati Territory. 106 Reduction in Force On September 19, 2023, the FDA issued a CRL regarding our NDA for neffy .
The non-cash charges primarily consisted of non-cash stock-based compensation of $5.8 million, acquired in-process research and development of $1.1 million, depreciation, amortization and accretion expense of $0.3 million, and change in fair value of warrant liability of $0.1 million. During the year ended December 31, 2021, net cash used in operating activities was $17.6 million.
The non-cash charges primarily consisted of non-cash stock-based compensation of $5.8 million, expense of acquired in-process research and development of $1.1 million, depreciation, amortization and accretion expense of $0.3 million, and change in fair value of warrant liability of $0.1 million.
If we obtain marketing approval for any of our product candidates, we will incur significant commercialization expenses for marketing, sales, manufacturing and distribution activities, and added expenditures to expand our operational, financial and management systems and increase personnel to support these operations.
If we obtain marketing approval for any of our product candidates, we will incur significant commercialization expenses for marketing, sales, manufacturing and distribution activities, and added expenditures to expand our operational, financial and management systems and increase personnel to support these operations. 105 We do not expect to generate any revenues from product sales unless and until we successfully obtain regulatory approval for one or more product candidates, if ever.
As, among other facts, the stockholders of ARS Pharma owned a majority of the combined company, the Merger was treated for accounting purposes as if ARS Pharma had acquired Silverback.
As, among other facts, the stockholders of privately-held ARS Pharma owned a majority of the combined company, the Merger was treated for accounting purposes as if ARS Pharma had acquired Silverback. As a result of the Merger being accounted for as if ARS Pharma had acquired Silverback, all financial statements prior to the Merger are of ARS Pharma.
We anticipate our general and administrative expenses will increase substantially in 2023 as we add sales and marketing personnel, infrastructure and programs to support pre-commercial activities, and if our product candidates receive marketing approval, commercialization activities. We also anticipate increased general and administrative personnel to support our operations, and higher patent and facility related costs.
We expect that our general and administrative expenses will increase substantially in 2024 as we add sales and marketing personnel, infrastructure and programs to support pre-commercial activities, and if our product candidates receive marketing approval, commercialization activities.
As of December 31, 2022, we had cash, cash equivalents, and short-term investments of $274.4 million. 96 We have incurred net losses from operations since our inception. Our net loss was $34.7 million for the year ended December 31, 2022 and as of December 31, 2022 we had an accumulated deficit of $76.9 million.
As of December 31, 2023, we had cash, cash equivalents, and short-term investments of $228.4 million. We have incurred net losses from operations since our inception. Our net losses were $54.4 million and $34.7 million for the years ended December 31, 2023 and 2022, respectively. As of December 31, 2023 we had an accumulated deficit of $131.3 million.
The non-cash charges primarily consisted of stock-based compensation of $2.8 million and depreciation, amortization and accretion expense of $0.2 million. Investing Activities During the year ended December 31, 2022, the cash and cash equivalents used in investing activities was primarily due to $0.2 million in purchases of property and equipment.
During the year ended December 31, 2022, the cash and cash equivalents used in investing activities was $0.2 million due to purchases of property and equipment.
This consisted primarily of a net loss of $20.2 million and an increase in our operating assets and liabilities of $0.4 million, partially offset by non-cash charges of $3.0 million.
This consisted primarily of a net loss of $54.4 million, a decrease in our operating liabilities of $5.9 million, an increase in our operating assets of $1.4 million, and non-cash charges of $2.4 million.
If the actual timing of the performance of services or the level of effort varies from the original estimates, we will adjust the accrual accordingly. Payments made to third parties under these arrangements in advance of the performance of the related services are recorded as prepaid expenses and other current assets until the services are rendered.
Payments made to third parties under these arrangements in advance of the performance of the related services are recorded as prepaid expenses and other current assets until the services are rendered.
Research and development expenses were $18.4 million and $20.3 million for the years ended December 31, 2022 and 2021, respectively. The decrease of $1.9 million was primarily due to a $3.1 million decrease in clinical trial costs associated with neffy and a $1.9 million decrease in stock-based compensation.
Research and development expenses were $20.3 million and $18.4 million for the years ended December 31, 2023 and 2022, respectively. The increase of $1.9 million was primarily due to a $2.1 million increase in stock-based compensation, a $1.1 million increase in payroll-related expenses, a $0.9 million increase in consulting fees, and a $0.5 million increase in other operating expenses.
We cannot determine with certainty the timing of initiation, the duration or the completion costs of current or future clinical trials and the manufacturing costs of our product candidates due to the inherently unpredictable nature of clinical development and manufacturing activities. Clinical development and manufacturing timelines, the probability of success and development costs can differ materially from expectations.
However, the timing for regulatory approvals is outside our control, may be delayed and is uncertain. We cannot determine with certainty the timing of initiation, the duration or the completion costs of current or future clinical trials and the manufacturing costs of our product candidates due to the inherently unpredictable nature of clinical development and manufacturing activities.
Revenue under collaboration agreements was $1.3 million and $5.5 million for the years ended December 31, 2022 and 2021, respectively.
Revenues under collaboration agreements were less than $0.1 million and $1.3 million for the years ended December 31, 2023 and 2022, respectively.
As of December 31, 2022, we had no accrued interest or penalties related to uncertain tax positions. Critical Accounting Policies and Significant Judgements and Estimates Our management’s discussion and analysis of our financial condition and results of operations are based on our consolidated financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”).
Critical Accounting Policies and Significant Judgments and Estimates Our management’s discussion and analysis of our financial condition and results of operations are based on our financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles (GAAP).
We are unable to estimate the timing or likelihood of achieving additional milestones or royalty payments under this agreement. We are also responsible for reimbursing Aegis for patent costs incurred in connection with prosecuting and maintaining patent rights that are specific to epinephrine or epinephrine products.
We are also required to make royalty payments in connection with the sale of products developed under that agreement. We are unable to estimate the timing or likelihood of achieving additional milestones or royalty payments under this agreement.
While our significant accounting policies and estimates are described in more detail in Note 2- Summary of Significant Accounting Policies to our consolidated financial statements, we believe the following accounting policies and estimates to be most critical to the preparation of our consolidated financial statements. 103 Revenue Our revenues generally consist of licenses and research services under license and collaboration agreements.
Actual results may differ from these estimates under different assumptions or conditions. While our significant accounting policies and estimates are described in more detail in Note 2- Summary of Significant Accounting Policies to our consolidated financial statements, we believe the following accounting policies and estimates to be most critical to the preparation of our consolidated financial statements.
Our clinical trials and manufacturing costs for the periods presented below reflect an allocation of expenses associated with personnel costs, equity-based compensation expense, and indirect costs incurred in support of overall research and development, such as facilities-related costs.
Our clinical, regulatory, manufacturing, and non-clinical development costs for the periods presented below reflect an allocation of expenses associated with personnel costs, equity-based compensation expense, and indirect costs incurred in support of overall research and development, such as facilities-related costs. 107 We expect that our research and development expenses will likely decrease in 2024 based on our planned clinical development and manufacturing activities, as we plan to transition to commercialization efforts for the potential launch of our first product in the second half of 2024.
Total Other Income (Expense). Total other income was $0.8 million for the year ended December 31, 2022 and total other expense was $0.8 million for the year ended December 31, 2021.
Other Income, Net. Other income, net was $13.2 million and $0.8 million for the years ended December 31, 2023 and 2022, respectively.
Further, a number of factors, including those outside of our control, could adversely impact the timing and duration of our product candidates’ or any future candidates’ development, which could increase our research and development expenses.
Further, a number of factors, including those outside of our control, could adversely impact the timing and duration of our product candidates’ or any future candidates’ development, which could increase our research and development expenses. 108 General and Administrative General and administrative expenses consist primarily of salaries, benefits, equity-based compensation for personnel in executive, finance, business development, sales and marketing and other corporate administrative functions.
We enter into contracts in the normal course of business with third-party contract organizations and vendors for clinical studies, manufacturing and other services and products. These contracts generally provide for termination after a notice period. To date, we have not recognized any reserves related to uncertain tax positions.
Annual rent expense is $0.2 million and is subject to annual increases of 3%, plus our share of operating expenses and taxes. We enter into contracts in the normal course of business with third-party contract organizations and vendors for clinical studies, manufacturing and other services and products. These contracts generally provide for termination after a notice period.
Cash flows The following table summarizes our cash flows for the years ended December 31, 2022 and 2021 (in thousands): Years Ended December 31, 2022 2021 Net cash and cash equivalents used in operating activities $ (40,078 ) $ (17,561 ) Net cash and cash equivalents used in investing activities (199 ) (55 ) Net cash and cash equivalents provided by financing activities 190,732 53,158 Net increase in cash and cash equivalents $ 150,455 $ 35,542 Operating Activities During the year ended December 31, 2022, net cash used in operating activities was $40.1 million.
As of December 31, 2023, we had cash, cash equivalents, and short-term investments of $228.4 million. 110 Cash flows The following table summarizes our cash flows for the years ended December 31, 2023 and 2022 (in thousands): Year Ended December 31, 2023 2022 Net cash and cash equivalents used in operating activities $ (59,266 ) $ (40,078 ) Net cash and cash equivalents used in investing activities (87,180 ) (199 ) Net cash and cash equivalents provided by financing activities 6,899 190,732 Net (decrease) increase in cash and cash equivalents $ (139,547 ) $ 150,455 Operating Activities During the year ended December 31, 2023, net cash used in operating activities was $59.3 million.
Financial Overview Revenues To date, we have not generated any revenues from the commercial sale of any products, and we may not generate revenues from the commercial sale of any products. We have signed collaboration and license agreements including supply and distribution for neffy with Alfresa Pharma in Japan and Pediatrix in China.
We have signed collaboration and license agreements including supply and distribution for neffy with Alfresa Pharma in Japan and Pediatrix in China.
Pursuant to the Termination Agreement with Recordati, we have payment obligations of up to €10.0 million contingent upon our achievement of certain regulatory and commercial milestones, and up to €5.0 million based on a low double-digit percentage of sales of sales of Recordati Licensed Product(s) in the Recordati Territory We are unable to estimate the timing or likelihood of achieving these milestones and sales-based payments under this agreement.
We are also responsible for reimbursing Aegis for patent costs incurred in connection with prosecuting and maintaining patent rights that are specific to epinephrine or epinephrine products. 112 Pursuant to the Termination Agreement with Recordati, we made a one-time upfront payment of €3.0 million, and have remaining payment obligations of up to €7.0 million contingent upon our achievement of certain regulatory and commercial milestones, and up to €5.0 million based on a low double-digit percentage of sales of Recordati Licensed Product(s) in the Recordati Territory.
Data from our studies of neffy demonstrated nasally delivered epinephrine reached blood levels comparable to those of already approved epinephrine injectable products.
Data from our studies of neffy demonstrated nasally delivered epinephrine reached blood levels comparable to those of already approved epinephrine injectable products, and produced statistically significant responses compared to injection on pharmacodynamic surrogates for efficacy even one minute after dosing with neffy .
In accordance with the terms of the agreement and plan of merger and reorganization, dated July 21, 2022, as amended on August 11, 2022 and October 25, 2022 (the “Merger Agreement”), Sabre Merger Sub, Inc. (“Merger Sub”), a wholly-owned subsidiary of Silverback, merged into ARS Pharma, with ARS Pharma surviving as Silverback’s wholly-owned subsidiary.
Merger On November 8, 2022 (the “Closing Date”), Silverback Therapeutics, Inc., a Delaware corporation (“Silverback”), now known as ARS Pharmaceuticals, Inc., completed its reverse merger (the “Merger”) with privately-held ARS Pharmaceuticals, Inc., in accordance with the terms of the agreement and plan of merger and reorganization, dated July 21, 2022, as amended on August 11, 2022 and October 25, 2022 (the “Merger Agreement”), whereby Sabre Merger Sub, Inc.
Our research and development accruals are estimated based on the level of services performed, progress of the studies, including the phase or completion of events, and contracted costs. The estimated costs of research and development provided, but not yet invoiced, are included in accrued liabilities on the balance sheet.
Accrued Research and Development We have entered into various agreements with CROs, CMOs, and other service providers. Our research and development accruals are estimated based on the level of services performed, progress of the studies, including the phase or completion of events, and contracted costs.
We also expect to incur added audit, legal, regulatory and tax-related services associated with maintaining compliance with exchange listing and SEC requirements, director and officer insurance premiums, board of director fees, and investor relations costs associated with operating as a public company following the Merger. 99 Total Other Income (Expense) Total other income (expense) consists primarily of interest expense from bank debt, interest income from our cash, cash equivalents, and investments, and changes in the fair value of our warrant liability prior to the Merger.
We expect to continue to incur audit, legal, regulatory and tax-related services associated with maintaining compliance with exchange listing and SEC requirements, director and officer insurance premiums, board of director fees, investor relations costs associated with operating as a public company, patent costs and defense, and general and administrative personnel.
Results of Operations Comparison of the Years Ended December 31, 2022 and 2021: The following table summarizes our results of operations for the years ended December 31, 2022 and 2021 (in thousands, except percentages): Years Ended December 31, Dollar % 2022 2021 Change Change Revenue under collaboration agreements $ 1,316 $ 5,506 $ (4,190 ) (76 %) Operating expenses: Research and development (1) 18,376 20,273 (1,897 ) (9 ) General and administrative (1) 18,456 4,687 13,769 294 Total operating expenses 36,832 24,960 11,872 48 Loss from operations (35,516 ) (19,454 ) (16,062 ) 83 Total other income (expense): 834 (789 ) 1,623 (206 ) Net loss (34,682 ) (20,243 ) (14,439 ) 71 Unrealized gain on available-for-sale securities 407 — 407 100 Comprehensive loss attributable to common stockholders $ (34,275 ) $ (20,243 ) $ (14,032 ) 69 % ______________ (1) Includes stock-based compensation expense as follows (in thousands): Years Ended December 31, 2022 2021 Research and development $ 213 $ 2,114 General and administrative 5,630 715 Total $ 5,843 $ 2,829 Revenues.
Results of Operations Comparison of the Years Ended December 31, 2023 and 2022: The following table summarizes our results of operations for the years ended December 31, 2023 and 2022 (in thousands, except percentages): Year Ended December 31, Dollar % 2023 2022 Change Change Revenue under collaboration agreements $ 30 $ 1,316 $ (1,286 ) (98 %) Operating expenses: Research and development (1) 20,266 18,376 1,890 10 General and administrative (1) 47,284 18,456 28,828 156 Total operating expenses 67,550 36,832 30,718 83 Loss from operations (67,520 ) (35,516 ) (32,004 ) 90 Total other income: 13,155 834 12,321 * Net loss (54,365 ) (34,682 ) (19,683 ) 57 Change in unrealized gains and losses on available-for-sale securities (358 ) 407 (765 ) (188 ) Comprehensive loss $ (54,723 ) $ (34,275 ) $ (20,448 ) 60 % ______________ (1) Includes stock-based compensation expense as follows (in thousands): * Not meaningful Year Ended December 31, 2023 2022 Research and development $ 2,274 $ 213 General and administrative 6,961 5,630 Total $ 9,235 $ 5,843 109 Revenues .
Material Cash Requirements Under our license agreement with Aegis, we have payment obligations of up to $20.0 million contingent upon our achievement of certain regulatory and commercial milestones and are required to make royalty payments in connection with the sale of products developed under that agreement.
Material Cash Requirements Under our license agreement with Aegis, we paid an aggregate $1.5 million for an upfront license fee and meeting certain regulatory milestones, and have remaining payment obligations of up to $18.5 million contingent upon our achievement of certain other regulatory and commercial milestones.
Years Ended December 31, 2022 2021 Clinical trials $ 8,894 $ 10,560 Manufacturing and non-clinical development 9,482 9,713 Total research and development expenses $ 18,376 $ 20,273 100 General and Administrative Expenses. General and administrative expenses were $18.5 million and $4.7 million for the years ended December 31, 2022 and 2021, respectively.
The following table summarizes our research and development expenses for the years ended December 31, 2023 and 2022 (in thousands): Year Ended December 31, 2023 2022 Clinical and regulatory $ 9,057 $ 8,894 Manufacturing and non-clinical development 11,209 9,482 Total research and development expenses $ 20,266 $ 18,376 General and Administrative Expenses.
During the year ended December 31, 2021, the cash and cash equivalents provided by financing activities was primarily due to $54.8 million of proceeds from the issuance of Series D convertible preferred stock in August 2021 plus $0.2 million from common stock option exercises, partially offset by $1.8 million repayments on the bank note.
During the year ended December 31, 2022, the cash and cash equivalents provided by financing activities was $190.7 million which consisted of $198.8 million in net proceeds from the Merger, $0.6 million of proceeds from stock option exercises and the employee stock purchase plan, partially offset by $8.7 million for repayment of the bank note.
On an ongoing basis, we evaluate our estimates and judgments, including those related to revenues recognized under collaboration agreements, accruals for research and development expenses and valuation of equity awards.
On an ongoing basis, we evaluate our estimates and judgments, including those related to accrued expenses, stock-based compensation, and valuation allowances for deferred tax assets.
Our NDA was accepted for review by FDA in the fourth quarter of 2022 with an anticipated mid-2023 PDUFA target action date and if our NDA is approved, we believe neffy will be the first “no needle, no injection” marketed epinephrine product for the emergency treatment of Type I allergic reactions.
We have also completed the additional nitrosamine testing based on the new draft guidance issued by the FDA in August 2023, and no measurable levels of nitrosamines were detected. If approved, we believe neffy will be the first “no needle, no injection” marketed epinephrine product for the emergency treatment of type I allergic reactions.
In October 2021, we entered into a lease agreement to rent office space with a lease commencement date of December 2021. The lease has a term of 38 months. Annual rent expense is $0.2 million and is subject to annual increases of 3%, plus our share of operating expenses and taxes.
We are unable to estimate the timing or likelihood of achieving these milestones and sales-based payments under this agreement. In October 2021, we entered into a lease agreement to rent office space with a lease commencement date of December 2021. The lease has a term of 38 months.
These aggregated decreases were partially offset by $1.1 million in in-process research and development acquired in the Merger, a $1.0 million increase in license fees for the milestone payment to Aegis upon the FDA’s acceptance of our US NDA filing, and a $0.9 million increase in regulatory consulting costs.
These aggregated increases were partially offset by a $1.0 million decrease in license milestone expenses, a $0.9 million decrease in in-process research and development expenses, a $0.5 million decrease in clinical trial costs associated with neffy, and a $0.3 million decrease in regulatory filing fees.
During the year ended December 31, 2021, the cash and cash equivalents used in investing activities was primarily due to $0.1 million in purchases of property and equipment. 101 Financing Activities During the year ended December 31, 2022, the cash and cash equivalents provided by financing activities was primarily due to $198.8 million in net proceeds from the Merger.
Investing Activities During the year ended December 31, 2023, the cash and cash equivalents used in investing activities was $87.2 million. This consisted primarily of purchases of short-term investments of $272.0 million, maturities of short-term investments of $185.0 million, and purchases of property and equipment of $0.2 million.
The increase of $13.8 million was primarily due to a $4.9 million increase in stock-based compensation of which $3.0 million was for the replacement of stock awards held by Silverback employees and directors in connection with the Merger and $1.3 million for the vesting of previously issued performance-based options, a $3.6 million increase in outside services associated with marketing and consulting, a $2.3 million increase in legal fees, a $2.2 million increase in payroll and related expenses, and a $0.6 million increase in insurance costs.
The increase of $28.8 million was primarily due to a $13.6 million increase in pre-commercial launch activities related to neffy , a $6.8 million increase in payroll-related expenses, a $2.6 million increase in consulting fees, a $1.3 million increase in stock-based compensation, a $0.7 million increase in insurance costs, a $0.7 million increase in legal expenses, a $0.7 million increase in general overhead, a $0.6 million increase in conference expenses, a $0.5 million increase in recruiting fees, a $0.3 million increase in professional fees for accounting, auditing and tax, and a $1.0 million increase in other operating expenses.
The difference of $1.6 million was primarily due to a $1.8 million increase in interest income from our cash, cash equivalents, and investments partially offset by a $0.1 million loss due to the change in fair value of the preferred stock warrant liability.
The increase of $12.3 million was primarily due to a $11.7 million increase in interest income from our cash, cash equivalents, and short-term investments, a $0.6 million decrease in interest expense due to the Silicon Valley Bank loan payoff in November 2022, and $0.3 million from the sale of in-process research and development obtained in the Merger.
Removed
We do not expect to generate any revenues from product sales unless and until we successfully obtain regulatory approval for one or more product candidates, if ever.
Added
Following the acceptance of our NDA in October 2022 for review by the FDA, on May 11, 2023, the FDA held a virtual meeting of its Pulmonary-Allergy Drugs Advisory Committee (“PADAC”).
Removed
Merger On November 8, 2022 (the “Closing Date”), privately-held ARS Pharmaceuticals, Inc. (“ARS Pharma ) merged with Silverback Therapeutics, Inc., a Delaware corporation (“Silverback”), a publicly traded company.
Added
At that meeting, on the question of whether the data from our neffy pharmacokinetic (“PK”)/pharmacodynamic (“PD”) results support a favorable benefit-risk assessment in adults for the emergency treatment of Type I allergic reactions including anaphylaxis, the PADAC voted 16 (yes) and 6 (no).
Removed
As a result of the Merger being accounted for as if ARS Pharma had acquired Silverback, the financial statements of ARS Pharma are presented as the historical financial statements of the combined company for all periods presented.
Added
On the question of whether the neffy PK/PD results support a favorable benefit-risk assessment in children ≥30 kg for the emergency treatment of Type I allergic reactions including anaphylaxis, the PADAC voted 17 (yes) and 5 (no).
Removed
We expect that our research and development expenses will likely decrease in 2023 based on our planned clinical development and manufacturing activities, as we plan to transition to commercialization efforts for the potential launch of our first product that year. However, the timing for regulatory approvals is outside our control, may be delayed and is uncertain.
Added
Although the FDA considers the recommendations of the PADAC, the recommendation by the PADAC is non-binding. 104 On September 19, 2023, the FDA issued a Complete Response Letter (“CRL”) for our NDA requesting completion of a PK/PD study assessing repeat doses of neffy compared to repeat doses of epinephrine injection product under allergen-induced allergic rhinitis.
Removed
General and Administrative General and administrative expenses consist primarily of salaries, benefits, equity-based compensation for personnel in executive, finance, business development, sales and marketing and other corporate administrative functions.
Added
This request came after the favorable benefit-risk assessment of the PADAC to approve neffy without need for additional studies. In addition, we had aligned with the FDA in May 2023, and re-confirmed in August 2023 to conduct this repeat-dose study under allergen-induced allergic rhinitis study as a post-marketing requirement as informative for labeling.
Removed
As a result of the Merger, the warrant liability was reclassified to equity and fair value adjustments are no longer required.
Added
The CRL also requested additional information on nitrosamine impurities to be tested based on new draft guidance issued in August 2023 after the neffy NDA submission. Our testing, based on methods in the older guidance, did not detect any nitrosamines above or close to the recommended acceptable daily intake limit for chronic exposure. neffy is for acute use.
Removed
The remaining decrease from 2021 to 2022 is due to the recognition of an upfront payment of $3.0 million under our collaboration and distribution agreement with Pediatrix signed in March 2021 relating to the issuance and delivery of a technology license, with no comparable activity in 2022.
Added
We held a type A meeting with the FDA to discuss the contents of the CRL on October 24, 2023. The FDA reiterated that no other information is required beyond the contents of the CRL.
Removed
As of December 31, 2022, we had cash, cash equivalents, and short-term investments of $274.4 million.
Added
The FDA also confirmed that the previously agreed design for the repeat-dose clinical study to evaluate the similarity of twice dosing injection and twice dosing neffy under allergen-induced allergic rhinitis will generate the necessary data to answer its outstanding questions regarding neffy .
Removed
In addition, we acquired $63.5 million in short-term investments through the Merger. Also, during the year ended December 31, 2022, we used cash of $8.7 million for repayment of the bank note.
Added
In addition, the neffy resubmission will be classified as Class 2, with an action expected within six months of receipt date.

… 51 more changes not shown on this page.

Other SPRY 10-K year-over-year comparisons