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What changed in Azitra, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Azitra, Inc.'s 2024 and 2025 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 2025 report.

+367 added−314 removedSource: 10-K (2026-02-27) vs 10-K (2024-12-31)

Top changes in Azitra, Inc.'s 2025 10-K

367 paragraphs added · 314 removed · 260 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

125 edited+18 added−23 removed312 unchanged
Biggest changeIf these third-party payers do not consider our product candidates to be cost-effective compared to other available therapies, they may not cover our product candidates after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our product candidates on a profitable basis.
Biggest changeIf these third-party payers do not consider our product candidates to be cost-effective compared to other available therapies, they may not cover our product candidates after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our product candidates on a profitable basis. 36 In order to secure coverage and reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the costs required to obtain FDA, EMA or other comparable regulatory approvals.
After submitting post-IND manufacturing reports, we have commenced operating activities for our Phase 1b clinical trial in December 2023, and we have dosed our first patient in August 2024.
After submitting post-IND manufacturing reports, we have commenced operating activities for our Phase 1b clinical trial in December 2023, and dosed our first patient in August 2024.
In August 2024, we obtained IND clearance from the FDA to commence a Phase 1/2 clinical trial in certain cancer patients undergoing EGFRi targeted therapy. In September 2024, we 1 obtained Fast Track designation by the FDA in this indication.
In August 2024, we obtained IND clearance from the FDA to commence a Phase 1/2 clinical trial in certain cancer patients undergoing EGFRi targeted therapy. In September 2024, we obtained Fast Track designation by the FDA in this indication.
ATR-04 Our ATR-04 product candidate is subject to one issued US patent, two pending US patent applications, and 20 pending foreign applications. These patents and patent applications represent two families of claims directed to auxotrophic strains of bacteria and their therapeutic use for treating disease. We have one issued US patent that covers ATR-04.
ATR-04 Our ATR-04 product candidate is subject to one issued US patent, two pending US patent applications, and 20 pending foreign applications. These patents and patent applications represent two families of claims directed to 20 auxotrophic strains of bacteria and their therapeutic use for treating disease. We have one issued US patent that covers ATR-04.
Furthermore, a clinical trial may only be started after a competent ethics committee has issued a favorable opinion on the clinical trial application in that country. 31 On January 31, 2022, the Clinical Trials Regulation (EU) No. 536/2014 replaced the current Clinical Trials Directive 2001/20/EC.
Furthermore, a clinical trial may only be started after a competent ethics committee has issued a favorable opinion on the clinical trial application in that country. On January 31, 2022, the Clinical Trials Regulation (EU) No. 536/2014 replaced the current Clinical Trials Directive 2001/20/EC.
A person or entity does not need to have actual knowledge of the federal anti-kickback statute or specific intent to violate it to have committed a violation; in addition, items or services resulting from a violation of the federal anti-kickback statute may constitute a false or fraudulent claim for purposes of the False Claims Act; • The Ethics in Patient Referrals Act, commonly referred to as the Stark Law, and its corresponding regulations, prohibit physicians from referring patients for designated health services (including outpatient drugs) reimbursed under the Medicare or Medicaid programs to entities with which the physicians or their immediate family members have a financial relationship or an ownership interest, subject to narrow regulatory exceptions, and prohibits those entities from submitting claims to Medicare or Medicaid for payment of items or services provided to a referred beneficiary; • The federal False Claims Act imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government claims for payment that are false or fraudulent or making a false statement to avoid, decrease, or conceal an obligation to pay money to the federal government; • Health Insurance Portability and Accountability Act of 1996, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program and also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.
A person or entity does not need to have actual knowledge of the federal anti-kickback statute or specific intent to violate it to have committed a violation; in addition, items or services resulting from a violation of the federal anti-kickback statute may constitute a false or fraudulent claim for purposes of the False Claims Act; • The Ethics in Patient Referrals Act, commonly referred to as the Stark Law, and its corresponding regulations, prohibit physicians from referring patients for designated health services (including outpatient drugs) reimbursed under the Medicare or Medicaid programs to entities with which the physicians or their immediate family members have a financial relationship or an ownership interest, subject to narrow regulatory exceptions, and prohibits those entities from submitting claims to Medicare or Medicaid for payment of items or services provided to a referred beneficiary; • The federal False Claims Act imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the 35 federal government claims for payment that are false or fraudulent or making a false statement to avoid, decrease, or conceal an obligation to pay money to the federal government; • Health Insurance Portability and Accountability Act of 1996, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program and also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.
The process regarding approval of medicinal products in the EU follows roughly the same lines as in the United States and likewise generally involves satisfactorily completing each of the following: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the applicable EU Good Laboratory Practice regulations; • submission to the relevant regulatory agencies in EU member states, or national authorities, of a clinical trial application, or CTA, for each clinical trial, which must be approved before human clinical trials may begin; • performance of adequate and well-controlled clinical trials to establish the safety and efficacy of the product for each proposed indication; • submission to the relevant national authorities of a Marketing Authorisation Application, or MAA, which includes the data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; • satisfactory completion of an inspection by the relevant national authorities of the manufacturing facility or facilities, including those of third parties, at which the product is produced to assess compliance with cGMP; • potential audits of the non-clinical and clinical trial sites that generated the data in support of the MAA; and • review and approval by the relevant national authority of the MAA before any commercial marketing, sale or shipment of the product.
The process regarding approval of medicinal products in the EU follows roughly the same lines as in the United States and likewise generally involves satisfactorily completing each of the following: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the applicable EU Good Laboratory Practice regulations; • submission to the relevant regulatory agencies in EU member states, or national authorities, of a clinical trial application, or CTA, for each clinical trial, which must be approved before human clinical trials may begin; • performance of adequate and well-controlled clinical trials to establish the safety and efficacy of the product for each proposed indication; • submission to the relevant national authorities of a Marketing Authorisation Application, or MAA, which includes the data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; 30 • satisfactory completion of an inspection by the relevant national authorities of the manufacturing facility or facilities, including those of third parties, at which the product is produced to assess compliance with cGMP; • potential audits of the non-clinical and clinical trial sites that generated the data in support of the MAA; and • review and approval by the relevant national authority of the MAA before any commercial marketing, sale or shipment of the product.
Any authorization that is not followed by the actual placing of the drug on the EU market (in case of centralized procedure) or on the market of the authorizing member state within three years after authorization will cease to be valid, the so-called “sunset clause." Orphan Drug Designation and Exclusivity The European Commission can grant orphan medicinal product designation to products for which the sponsor can establish that it is intended for the diagnosis, prevention, or treatment of (1) a life-threatening or chronically debilitating condition affecting not more than five in 10,000 people in the EU, or (2) a life threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that sales of the drug in the EU would generate a sufficient return to justify the necessary investment.
Any authorization that is not followed by the actual placing of the drug on the EU market (in case of centralized procedure) or on the market of the authorizing member state within three years after authorization will cease to be valid, the so-called “sunset clause." Orphan Drug Designation and Exclusivity The European Commission can grant orphan medicinal product designation to products for which the sponsor can establish that it is intended for the diagnosis, prevention, or treatment of (1) a life-threatening or chronically debilitating condition affecting not more than five in 10,000 people in the EU, or (2) a life threatening, 33 seriously debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that sales of the drug in the EU would generate a sufficient return to justify the necessary investment.
Such conditional approvals may be granted for products (including medicines designated as orphan medicinal products), if (1) the risk-benefit balance of the product is positive, (2) it is likely that the applicant will be in a position to provide the required comprehensive clinical trial data, (3) the product fulfills unmet medical needs, and (4) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required.
Such conditional approvals may be granted for products (including medicines designated as orphan medicinal products), if (1) the risk-benefit balance of the product is positive, (2) it is likely that the applicant will be in a position to provide the required comprehensive clinical trial 32 data, (3) the product fulfills unmet medical needs, and (4) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required.
It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry In addition, in response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid Innovation which will be evaluated on their 38 ability to lower the cost of drugs, promote accessibility, and improve quality of care.
It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry In addition, in response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid Innovation which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.
Finally, data from an ex vivo healthy human skin model demonstrate that a single topical dose of ATR-12 administered at the maximum intended dose of 10 9 CFU/g delivers enough active rhLEKTI-D6 into the lower layers of the stratum corneum to effectively inhibit the protease, kallikrein 5, or KLK5, at levels typically observed in patients with Netherton syndrome.
Finally, data from an ex vivo healthy human skin model demonstrate that a single topical dose of ATR-12-351 administered at the maximum intended dose of 10 9 CFU/g delivers enough active rhLEKTI-D6 into the lower layers of the stratum corneum to effectively inhibit the protease, kallikrein 5, or KLK5, at levels typically observed in patients with Netherton syndrome.
He also worked on the turnaround of Pharmacyclics, which subsequently sold to Abbvie for approximately $21 billion in 2015. Before that, Mr. Salva spent almost a decade in life sciences venture capital. Mr. Whitfill served as associate research scientist and currently serves as assistant professor adjunct at Yale University with appointments in the Departments of Pediatrics and Emergency Medicine.
He also worked on the turnaround of Pharmacyclics, which subsequently sold to Abbvie for approximately $21 billion in 2015. Before that, Mr. Salva spent almost a decade in life sciences venture capital. Dr. Whitfill served as associate research scientist and currently serves as assistant professor adjunct at Yale University with appointments in the Departments of Pediatrics and Emergency Medicine.
Other potential consequences include, among other things: 28 • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending BLAs or supplements to approved BLAs, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending BLAs or supplements to approved BLAs, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
In preclinical studies, we have shown that S. epidermidis homes to layers below the stratum corneum and delivers proteins into the deeper epidermis. To expand upon our recombinant protein construction capabilities, we have acquired an exclusive license to proprietary technology that disguises our genetically engineered DNA sequences to enable the production of proteins in previously intractable bacterial species.
In preclinical studies, we have shown that S. epidermidis homes to layers below the stratum corneum and delivers proteins into the deeper epidermis. 5 To expand upon our recombinant protein construction capabilities, we have acquired an exclusive license to proprietary technology that disguises our genetically engineered DNA sequences to enable the production of proteins in previously intractable bacterial species.
Our solution – ATR-12 for the treatment of Netherton syndrome ATR-12 is a topical ointment containing an S. epidermidis strain, SE351, that has been genetically modified to express LEKTI from the chromosome. The SE351 strain has also been engineered to be auxotrophic for D-alanine, which means it cannot survive without the exogenous D-alanine nutrient provided in the formulation.
Our solution – ATR-12 for the treatment of Netherton syndrome ATR-12-351 is a topical ointment containing an S. epidermidis strain, SE351, that has been genetically modified to express LEKTI from the chromosome. The SE351 strain has also been engineered to be auxotrophic for D-alanine, which means it cannot survive without the exogenous D-alanine nutrient provided in the formulation.
Ltd. is developing DWP708 in Korea. Intellectual Property Overview We actively seek to protect our proprietary technology, inventions, improvements to inventions and other intellectual property that is commercially important to the development of our business by a variety of means, such as seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties.
Ltd. is developing DWP708 in Korea. 19 Intellectual Property Overview We actively seek to protect our proprietary technology, inventions, improvements to inventions and other intellectual property that is commercially important to the development of our business by a variety of means, such as seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties.
Moreover, a sponsor who chooses not to submit a rare pediatric disease designation request may nonetheless receive a PRV upon approval of their marketing application if they request such a voucher in their original. marketing application and meet all of the eligibility criteria. If a PRV is received, it may be sold or transferred an unlimited number of times.
Moreover, a sponsor who chooses not to submit a rare pediatric disease designation request may nonetheless receive a PRV upon approval of their 27 marketing application if they request such a voucher in their original. marketing application and meet all of the eligibility criteria. If a PRV is received, it may be sold or transferred an unlimited number of times.
We seek to protect our proprietary technology and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific 21 advisors, contractors and others who may have access to proprietary information, under which they are bound to assign to us inventions made during the term of their employment or term of service.
We seek to protect our proprietary technology and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and others who may have access to proprietary information, under which they are bound to assign to us inventions made during the term of their employment or term of service.
We believe our collaboration with the Carnegie Mellon based team provides us with a scalable and modification tolerant way to accelerate therapeutic discoveries within our microbial library. 5 The Delivery of our Microbially Produced Drugs The delivery of genetically engineered proteins to the subcutaneous target sites is hindered by the natural barrier and the defenses of the stratum corneum.
We believe our collaboration with the Carnegie Mellon based team provides us with a scalable and modification tolerant way to accelerate therapeutic discoveries within our microbial library. The Delivery of our Microbially Produced Drugs The delivery of genetically engineered proteins to the subcutaneous target sites is hindered by the natural barrier and the defenses of the stratum corneum.
EGFRi-Associated Rash To date, no drug has been specifically approved by the FDA for the treatment of EGFRi-associated rash. The majority of patients (estimated to be up to 90%) treated continuously with anti-EGFR therapies suffer from dermatological adverse events, especially papulopustular rash, pruritus (itching), xerosis (dryness), and paronychia 19 (nail infections).
EGFRi-Associated Rash To date, no drug has been specifically approved by the FDA for the treatment of EGFRi-associated rash. The majority of patients (estimated to be up to 90%) treated continuously with anti-EGFR therapies suffer from dermatological adverse events, especially papulopustular rash, pruritus (itching), xerosis (dryness), and paronychia (nail infections).
It is also a key factor in certain malignancies, and its activity enhances tumor growth, invasion, and metastasis. While systemic exposure to EGFRi agents suppresses EGFR at the target cancer site, it also suppresses EGFR throughout the body. In the skin, EGFR regulates multiple keratinocyte functions including proliferation, adhesion and migration, survival, and differentiation.
It is also a key factor in certain 11 malignancies, and its activity enhances tumor growth, invasion, and metastasis. While systemic exposure to EGFRi agents suppresses EGFR at the target cancer site, it also suppresses EGFR throughout the body. In the skin, EGFR regulates multiple keratinocyte functions including proliferation, adhesion and migration, survival, and differentiation.
The ability of SE484 to reduce IL-36γ/IL-8 levels as well as its activity against S. aureus and the engineered D-alanine auxotrophy enabled us to nominate strain SE484 for use as the active microbe in the ATR-04 drug product formulation to form the basis of a treatment and reduce the severity of EGFRi rash.
The ability of SE484 to reduce IL-36γ/IL-8 levels as well as its activity against S. aureus and the engineered D-alanine auxotrophy enabled us to nominate strain SE484 for use as the active microbe in the ATR-04-484 drug product formulation to form the basis of a treatment and reduce the severity of EGFRi rash.
Pursuant to our agreement with Fred Hutch, we obtained an exclusive worldwide license under certain patents related to SyMPL technologies developed and owned by Fred Hutch to develop, make, manufacture, have manufactured, distribute, have distributed, use, research, improve, import, offer to sell and sell and otherwise commercialize products that are covered by such patents.
Pursuant to our agreement with Fred Hutch, we obtained an exclusive worldwide license under certain patents related to SyMPL technologies developed and owned by Fred Hutch to develop, make, manufacture, have manufactured, distribute, have distributed, use, research, improve, import, offer to sell and sell 21 and otherwise commercialize products that are covered by such patents.
We, our manufacturers and clinical research organizations may also be subject to regulations under other foreign, federal, state and local laws, including, but not limited to, the U.S. 22 Occupational Safety and Health Act, the Resource Conservation and Recovery Act, the Clean Air Act and import, export and customs regulations as well as the laws and regulations of other countries.
We, our manufacturers and clinical research organizations may also be subject to regulations under other foreign, federal, state and local laws, including, but not limited to, the U.S. Occupational Safety and Health Act, the Resource Conservation and Recovery Act, the Clean Air Act and import, export and customs regulations as well as the laws and regulations of other countries.
The CHMP is composed of experts nominated by each member state’s national authority for medicinal products, with one of them appointed to act as Rapporteur for the co-ordination of the 32 evaluation with the possible assistance of a further member of the Committee acting as a Co-Rapporteur. After approval, the Rapporteur(s) continue to monitor the product throughout its life cycle.
The CHMP is composed of experts nominated by each member state’s national authority for medicinal products, with one of them appointed to act as Rapporteur for the co-ordination of the evaluation with the possible assistance of a further member of the Committee acting as a Co-Rapporteur. After approval, the Rapporteur(s) continue to monitor the product throughout its life cycle.
We have also collected other species in our library that includes roughly 60 different skin commensal species that can also be screened for therapeutic purposes. Figure 1. Representative Species in Azitra Microbial Library Predictive Analysis of Our Microbial Library The biopharmaceutical industry has seen success in identifying and isolating thousands of bacterial species.
We have also collected other species in our library that includes roughly 60 different skin commensal species that can also be screened for therapeutic purposes. 4 Figure 1. Representative Species in Azitra Microbial Library Predictive Analysis of Our Microbial Library The biopharmaceutical industry has seen success in identifying and isolating thousands of bacterial species.
The appearance of the papulopustular rash is a dose-dependent skin drug reaction, which usually develops in the first one to two weeks and peaks at three to four weeks on therapy. The intensity of the rash may start to decrease after two 11 weeks but can persists over the entire course of EGFRi treatment.
The appearance of the papulopustular rash is a dose-dependent skin drug reaction, which usually develops in the first one to two weeks and peaks at three to four weeks on therapy. The intensity of the rash may start to decrease after two weeks but can persists over the entire course of EGFRi treatment.
Clinical trials are usually conducted in three sequential phases, but the phases may overlap or be combined. Annual progress detailing the results of the clinical trial phases must be submitted to the FDA. 24 • Phase 1 clinical trials are normally conducted in small groups of healthy volunteers to assess safety and tolerability of various dosing regimens and pharmacokinetics.
Clinical trials are usually conducted in three sequential phases, but the phases may overlap or be combined. Annual progress detailing the results of the clinical trial phases must be submitted to the FDA. • Phase 1 clinical trials are normally conducted in small groups of healthy volunteers to assess safety and tolerability of various dosing regimens and pharmacokinetics.
If we seek to make certain changes to an approved product, such as certain manufacturing changes, we may need FDA review and approval before the change can be implemented. 26 While physicians may use products for indications that have not been approved by the FDA, we may not label or promote the product for an indication that has not been approved.
If we seek to make certain changes to an approved product, such as certain manufacturing changes, we may need FDA review and approval before the change can be implemented. While physicians may use products for indications that have not been approved by the FDA, we may not label or promote the product for an indication that has not been approved.
S. epidermidis is a gram-positive bacterium that is ubiquitous in the human skin and mucosal flora. As one of 4 the earliest colonizers of the skin, S. epidermidis plays an important role in cutaneous immunity and maintaining microbial community homeostasis. S. epidermidis is known to have a beneficial relationship with its host as a skin commensal.
S. epidermidis is a gram-positive bacterium that is ubiquitous in the human skin and mucosal flora. As one of the earliest colonizers of the skin, S. epidermidis plays an important role in cutaneous immunity and maintaining microbial community homeostasis. S. epidermidis is known to have a beneficial relationship with its host as a skin commensal.
Our solution – ATR-04 for the treatment of EGFRi-associated rash ATR-04 is our formulated, drug product candidate for the treatment of EGFRi associated rash. It includes a strain of S. epidermidis strain that was selected from our microbial strain library, based on desired properties of IL-36γ reduction and inhibition of S. aureus and its biofilms.
Our solution – ATR-04 for the treatment of EGFRi-associated rash ATR-04-484 is our formulated, drug product candidate for the treatment of EGFRi associated rash. It includes a strain of S. epidermidis that was selected from our microbial strain library, based on desired properties of IL-36γ reduction and inhibition of S. aureus and its biofilms.
Then, we nominated this candidate for use as the active microbe in the ATR-04 drug product formulation. To test the ability of SE484 to reduce IL-36γ on a skin-like model, erlotinib was used to induce IL-36γ secretion on reconstructed human epidermis, or RHE.
Then, we nominated this candidate for use as the active microbe in the ATR-04-484 drug product formulation. To test the ability of SE484 to reduce IL-36γ on a skin-like model, erlotinib was used to induce IL-36γ secretion on reconstructed human epidermis, or RHE.
Both U.S. and non-U.S. manufacturing establishments must register and provide additional information to the FDA upon their initial participation in the manufacturing process. Any product manufactured by or imported from a facility that has not registered, whether 25 U.S. or non-U.S., is deemed misbranded under the FDCA.
Both U.S. and non-U.S. manufacturing establishments must register and provide additional information to the FDA upon their initial participation in the manufacturing process. Any product manufactured by or imported from a facility that has not registered, whether U.S. or non-U.S., is deemed misbranded under the FDCA.
ATR-04 is a topical application intended to address the papulopustular rash experienced by cancer patients undergoing epidermal growth factor receptor inhibitor, or EGFRi, targeted therapy. We believe this product candidate represents a potential $1 billion global sales opportunity by 2030.
ATR-04-484 is a topical application intended to address the papulopustular rash experienced by cancer patients undergoing epidermal growth factor receptor inhibitor, or EGFRi, targeted therapy. We believe this product candidate represents a potential $1 billion global sales opportunity by 2030.
We believe our genetic engineering techniques and technologies have 3 applicability outside of the field of medicine, including cosmetics and in the generation of clean fuels and bioremediation. • Leverage our academic partnerships. We currently have partnerships with investigators at the Fred Hutchinson Cancer Center, Yale University, Duke University and Carnegie Mellon University.
We believe our genetic engineering techniques and technologies have applicability outside of the field of medicine, including cosmetics and in the generation of clean fuels and bioremediation. • Leverage our academic partnerships. We currently have partnerships with investigators at the Fred Hutchinson Cancer Center, Yale University, Duke University and Carnegie Mellon University.
Not only does the “stealth by engineering” approach enable transformations in genetically intractable bacterial strains, but it has also been shown to drastically increase transformational efficiency. 6 Proof of principle experiments have shown improvements of over 10,000x in yields of genetically engineered colonies.
Not only does the “stealth by engineering” approach enable transformations in genetically intractable bacterial strains, but it has also been shown to drastically increase transformational efficiency. Proof of principle experiments have shown improvements of over 10,000x in yields of genetically engineered colonies.
This order issued by the FDA would delay either a proposed clinical trial or cause delay in initiation of a phase of an ongoing clinical trial, until all outstanding concerns have been adequately addressed and the FDA has notified the company that investigations may proceed.
This order issued by the FDA would delay either a proposed 23 clinical trial or cause delay in initiation of a phase of an ongoing clinical trial, until all outstanding concerns have been adequately addressed and the FDA has notified the company that investigations may proceed.
Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs.
Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs 37 under Medicare, and reform government program reimbursement methodologies for drugs.
We believe we can reduce discontinuation rate in patients undergoing EGFRi therapy and thus increase compliance. 12 • Higher quality of life. Many patients on EGFRi therapy report a poor quality of life due to adverse events and papulopustular rashes. Current treatment options fail to adequately reduce these adverse events.
We believe we can reduce discontinuation rate in patients undergoing EGFRi therapy and thus increase compliance. • Higher quality of life. Many patients on EGFRi therapy report a poor quality of life due to adverse events and papulopustular rashes. Current treatment options fail to adequately reduce these adverse events.
Overuse of topical steroids can even aggravate the defective skin barrier by inducing loss of the stratum corneum. Systemic retinoids have shown varying degrees of efficacy in Netherton syndrome, but also carry bone toxicity and teratogenicity as adverse effects.
Overuse of topical steroids can even aggravate the defective skin barrier by inducing loss of the stratum corneum. Systemic retinoids have shown varying degrees of efficacy in Netherton syndrome but 18 also carry bone toxicity and teratogenicity as adverse effects.
The failure to comply with the applicable requirements at any time during the product development process, including preclinical testing, clinical testing, the approval process or post-approval process, may subject an applicant to delays in the conduct of clinical trials, regulatory review and approval, and/or administrative or judicial sanctions.
The failure to comply with the applicable requirements at any time during the product development process, including preclinical testing, clinical testing, the approval process or post-approval process, may subject an applicant 22 to delays in the conduct of clinical trials, regulatory review and approval, and/or administrative or judicial sanctions.
After an 27 emergency has been designated, the FDA may issue an Emergency Use Authorization, or EUA, for the use of a specific product based on criteria established by the FDCA. An EUA is product specific and is subject to specific conditions and restrictions. Once the emergency underlying the EUA ends, then the EUA terminates.
After an emergency has been designated, the FDA may issue an Emergency Use Authorization, or EUA, for the use of a specific product based on criteria established by the FDCA. An EUA is product specific and is subject to specific conditions and restrictions. Once the emergency underlying the EUA ends, then the EUA terminates.
While we believe that our knowledge, experience and scientific 18 resources provide us with competitive advantages, we face potential competition from many different sources, including other biopharmaceutical companies, academic institutions and governmental agencies as well as public and private research institutions.
While we believe that our knowledge, experience and scientific resources provide us with competitive advantages, we face potential competition from many different sources, including other biopharmaceutical companies, academic institutions and governmental agencies as well as public and private research institutions.
Phase 3 clinical trials are undertaken to further evaluate, in a larger number of patients, dosage, provide substantial evidence of clinical efficacy and further test for safety in an expanded and diverse patient population at multiple, geographically dispersed clinical trial sites.
Phase 3 clinical trials are 24 undertaken to further evaluate, in a larger number of patients, dosage, provide substantial evidence of clinical efficacy and further test for safety in an expanded and diverse patient population at multiple, geographically dispersed clinical trial sites.
The period of exclusivity begins on the date that the marketing application is approved by the FDA and applies only to the indication for which the product has been designated. The FDA may approve a second application for the same product for a different use or a subsequent application for a different drug for the same 29 indication.
The period of exclusivity begins on the date that the marketing application is approved by the FDA and applies only to the indication for which the product has been designated. The FDA may approve a second application for the same product for a different use or a subsequent application for a different drug for the same indication.
Together, we expect these mechanisms of action to lead to significant reductions in rash severity among patients undergoing EGFRi therapy. We believe that ATR-04 has the potential to address current limitations to treatment of EGFRi-associated rash: • Reduced antibiotic use.
Together, we expect these mechanisms of action to lead to significant reductions in rash severity among patients undergoing EGFRi therapy. 12 We believe that ATR-04 has the potential to address current limitations to treatment of EGFRi-associated rash: • Reduced antibiotic use.
We believe that this patent gives us broad protection for using recombinant bacteria to treat skin diseases and disorders. through its expiration in May 2035. 20 Patent applications directed to our most advanced programs are summarized below.
We believe that this patent gives us broad protection for using recombinant bacteria to treat skin diseases and disorders. through its expiration in May 2035. Patent applications directed to our most advanced programs are summarized below.
The applicable regulations aim to ensure that information provided by holders of marketing authorizations regarding their products is truthful, balanced and accurately reflects the safety and efficacy claims authorized by the 35 EMA or by the national authority of the authorizing member state.
The applicable regulations aim to ensure that information provided by holders of marketing authorizations regarding their products is truthful, balanced and accurately reflects the safety and efficacy claims authorized by the EMA or by the national authority of the authorizing member state.
The Pediatric Committee of the EMA, or PDCO, may grant deferrals for some medicines, allowing a company to delay development of the medicine in children until there is enough information to 33 demonstrate its effectiveness and safety in adults.
The Pediatric Committee of the EMA, or PDCO, may grant deferrals for some medicines, allowing a company to delay development of the medicine in children until there is enough information to demonstrate its effectiveness and safety in adults.
In addition, emphasis on managed care in the United States has increased and we expect will continue to increase the pressure on 37 drug pricing. Coverage policies, third-party reimbursement rates and drug pricing regulation may change at any time.
In addition, emphasis on managed care in the United States has increased and we expect will continue to increase the pressure on drug pricing. Coverage policies, third-party reimbursement rates and drug pricing regulation may change at any time.
Information on the operation of the Public Reference Room can be obtained by calling the SEC at 1-800-SEC-0330. The SEC also maintains an internet site that contains reports and other information regarding our filings at www.sec.gov. 39
Information on the operation of the Public Reference Room can be obtained by calling the SEC at 1-800-SEC-0330. The SEC also maintains an internet site that contains reports and other information regarding our filings at www.sec.gov.
For more information related to the intellectual property acquired pursuant to the Fred Hutch license agreement, see the section titled “ Licenses and Intellectual Property Rights - Exclusive License Agreement with Fred Hutchinson Cancer Center .” Our Product Candidates ATR-12 for the treatment of Netherton syndrome ATR-12 is our proprietary and patent-pending drug candidate that contains a novel strain of S. epidermidis which has been genetically modified to express and secrete an active fragment of the full-length protein called the lympho-epithelial Kazal-type related inhibitor, or LEKTI.
For more information related to the intellectual property acquired pursuant to the Fred Hutch license agreement, see the section titled “ Licenses and Intellectual Property Rights - Exclusive License Agreement with Fred Hutchinson Cancer Center .” Our Product Candidates ATR-12 for the treatment of Netherton syndrome ATR-12 is our proprietary and patent-pending drug programe that contains a novel strain of S. epidermidis called SE351, which has been genetically modified to express and secrete an active fragment of the full-length protein called the lympho-epithelial Kazal-type related inhibitor, or LEKTI.
Salva, our chief executive officer, and Travis Whitfill, our co-founder and chief operating officer, who have more than 35 years of combined experience in the management of biotechnology companies and healthcare investing. Mr. Salva was previously a co-founder of Acerta Pharma, which was sold to AstraZeneca for approximately $6.3 billion in a staged acquisition beginning in 2016.
Travis Whitfill MPH, our co-founder and chief operating officer, who have more than 35 years of combined experience in the management of biotechnology companies and healthcare investing. Mr. Salva was previously a co-founder of Acerta Pharma, which was sold to AstraZeneca for approximately $6.3 billion in a staged acquisition beginning in 2016.
Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar (abbreviated) 34 application.
Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar (abbreviated) application.
Our initial focus is on the development of our current product candidates, including: • ATR-12 , a genetically modified strain of S. epidermidis for treating the orphan disease, Netherton syndrome, a chronic and sometimes fatal disease of the skin estimated to affect approximately one to nine in every 100,000, but its prevalence may be underestimated due to misdiagnosis caused by similarities to other skin diseases.
Our initial focus is on the development of our current programs, including: • ATR-12 , a genetically modified strain of S. epidermidis for treating the orphan disease, Netherton syndrome, a chronic and sometimes fatal disease of the skin estimated to affect approximately one to nine in every 100,000, but its prevalence may be underestimated due to misdiagnosis caused by similarities to other skin diseases.
Total LEKTI activity levels were obtained by adding the pmol amounts through layers 1 to 30 of placebo (grey bars) or ATR-12 (black bars) samples. Data are the average ± a standard deviation (SD) of 3 independent samples (N = 3).
Total LEKTI activity levels were obtained by adding the pmol amounts through layers 1 to 30 of vehicle (grey bars) or ATR-12 (black bars) samples. Data are the average ± a standard deviation (SD) of 3 independent samples (N = 3).
Full length human LETKI, a 15-domain protein (145 kDa), is too large for reliable bacterial expression and secretion. Given evidence 8 that fragments of the full-length protein are sufficient to counter the dysregulated skin serine protease activity observed in Netherton syndrome patients, we selected D6 for recombinant expression in S. epidermidis .
Full length human LEKTI, a 15-domain protein (145 kDa), is too large for reliable bacterial expression and secretion. Given evidence that fragments of the full-length protein are sufficient to counter the dysregulated skin serine protease activity observed in Netherton syndrome patients, we selected D6 for recombinant expression in S. epidermidis .
The steps usually required to be taken before a new biologic may be marketed in the U.S. generally include: • completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices regulation; • submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; • approval by an independent Institutional Review Board, or IRB, or ethics committee at each treatment site before the trial is commenced; • approval of an Institutional Biologics Committee or similar committee at each treatment site, where applicable, before the trial is commenced; • performance of adequate and well controlled human clinical trials to establish the safety, purity and potency of the proposed biologic product candidate for its proposed indication for use; • submission of data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; • preparation of and submission to the FDA of a BLA after completion of all pivotal clinical trials; • satisfactory completion of an FDA Advisory Committee review, if applicable; • a determination by the FDA within 60 days of its receipt of a BLA to file the application for review; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP standards and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and of selected clinical investigation sites to assess compliance with Good Clinical Practices, or GCP; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with CGP requirements and the integrity of clinical data in support of the BLA; • payment of user fees and securing FDA approval of the BLA for the proposed indication for use; • FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States; and • compliance with any post-approval requirements, including REMS and any post-approval studies required by the FDA. 23 Preclinical Studies and Investigational New Drug Application Preclinical tests include laboratory evaluations of product chemistry, formulation and stability, as well as animal studies to evaluate the potential for efficacy and toxicity in animals.
The steps usually required to be taken before a new biologic may be marketed in the U.S. generally include: • completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices regulation; • submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; • approval by an independent Institutional Review Board, or IRB, or ethics committee at each treatment site before the trial is commenced; • approval of an Institutional Biologics Committee or similar committee at each treatment site, where applicable, before the trial is commenced; • performance of adequate and well controlled human clinical trials to establish the safety, purity and potency of the proposed biologic product candidate for its proposed indication for use; • submission of data supporting safety and efficacy as well as detailed information on the manufacture and composition of the product in clinical development and proposed labeling; • preparation of and submission to the FDA of a BLA after completion of all pivotal clinical trials; • satisfactory completion of an FDA Advisory Committee review, if applicable; • a determination by the FDA within 60 days of its receipt of a BLA to file the application for review; • satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP standards and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and of selected clinical investigation sites to assess compliance with Good Clinical Practices, or GCP; • satisfactory completion of any FDA audits of the non-clinical and clinical trial sites to assure compliance with CGP requirements and the integrity of clinical data in support of the BLA; • payment of user fees and securing FDA approval of the BLA for the proposed indication for use; • FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States; and • compliance with any post-approval requirements, including REMS and any post-approval studies required by the FDA.
Fast Track, Breakthrough Therapy and Priority Review Designations The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condition, or in the event of an emergency. These programs are Fast Track designation, breakthrough therapy designation and priority review designation.
Fast Track, Breakthrough Therapy and Priority Review Designations The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condition, or in the event of an emergency.
The technology from the Fred Hutchinson Cancer Center, or Fred Hutch, expands the universe of bacterial species that can be genetically modified. It is based upon a restriction modification system-silent SyMPL toolset. The SyMPL technology platform makes human-made DNA invisible to the bacteria’s defenses. In theory, the method can be applied to any type of bacteria.
The technology from the Fred Hutch expands the universe of bacterial species that can be genetically modified. It is based upon a restriction modification system-silent SyMPL toolset. The SyMPL technology platform makes human-made DNA invisible to the bacteria’s defenses. In theory, the method can be applied to any type of bacteria.
ATR-04 for the Treatment of EGFRi-Associated Rash ATR-04 is our proprietary and patent-pending drug candidate that contains a novel strain of S. epidermidis , SE484, which has been genetically modified to be auxotrophic tor D-alanine and inhibits both S.aureus and IL-36γ.
ATR-04 for the Treatment of EGFRi-Associated Rash ATR-04-484 is our proprietary and patent-pending drug candidate that contains a novel strain of S. epidermidis , SE484, which has been genetically modified to be auxotrophic tor D-alanine and inhibits both S.aureus and IL-36γ Interleukin-36 gamma , or IL-36γ.
Statistical analysis was carried out using two-way ANOVA, and ** represents p Figure 4: LETKI activity in Placebo and ATR-12-Treated Skin Samples Following 0- and 8-hour Incubation In addition, a single therapeutic dose of ATR-12 over 24-hour incubation yielded ~2-fold higher LEKTI activity compared to 8-hour incubation. This indicates continuous production of functional rhLEKTI-D6 by ATR-12 over time.
Statistical analysis was carried out using two-way ANOVA, and ** represents p 9 Figure 4: LEKTI activity in Vehicle and ATR-12-Treated Skin Samples Following 0- and 8-hour Incubation In addition, a single therapeutic dose of ATR-12-351 over 24-hour incubation yielded ~2-fold higher LEKTI activity compared to 8-hour incubation. This indicates continuous production of functional rhLEKTI-D6 by ATR-12 over time.
Amounts of LEKTI activity in layers extracted were from 9 tape strip samples from ex vivo human skin treated with placebo and ATR-12. The collection proceeded right after skin application (T = 0 hours, white bars) or after 8 hours incubation at 30°C (T = 8 hours, black bars).
Amounts of LEKTI activity in layers extracted were from tape strip samples from ex vivo human skin treated with vehicle and ATR-12-351. The collection proceeded right after skin application (T = 0 hours, white bars) or after 8 hours incubation at 30°C (T = 8 hours, black bars).
Figure 5: LETKI activity in Placebo and ATR-12-Treated Skin Samples Following 24-hour Incubation In vitro stoichiometry work performed by Azitra indicates that KLK5 requires 2 molar equivalents on the rhLEKTI-D6 protein for inhibition (as measured by IC 50 ).
Figure 5: LEKTI activity in Vehicle and ATR-12-Treated Skin Samples Following 24-hour Incubation In vitro stoichiometry work performed by Azitra indicates that KLK5 requires 2 molar equivalents on the rhLEKTI-D6 protein for inhibition (as measured by IC 50 ).
We expect to report initial safety results in the first half of 2025. • ATR-04 , a genetically modified strain of S. epidermidis for treating the papulopustular rash experienced by cancer patients undergoing epidermal growth factor receptor inhibitor, or EGFRi, targeted therapy.
We reported initial safety results in the first half of 2025. • ATR-04 , a genetically modified strain of S. epidermidis for treating the papulopustular rash experienced by cancer patients undergoing epidermal growth factor receptor inhibitor, or EGFRi, targeted therapy.
The species has shown inhibition of the pathogenic strain, Staphylococcus aureus, or S. aureus, as well as the strain Propionibacterium acnes , or P. acnes . S. epidermidis induces keratinocytes to produce antimicrobial peptides and produces non-inflammatory T cell accumulation of both CD4+ and CD8+ T cells via immune cell signaling.
The species has shown inhibition of the pathogenic strain, Staphylococcus aureus, or S. aureus, as well as the strain Cutibacterium acnes , or C. acnes . S. epidermidis induces keratinocytes to produce antimicrobial peptides and produces non-inflammatory T cell accumulation of both CD4+ and CD8+ T cells via immune cell signaling.
We expect to dose the first patient in the Phase 1/2 clinical trial in the first half of 2025. • ATR-01 , a genetically modified strain of S. epidermidis that expresses an engineered recombinant human filaggrin protein for treating ichthyosis vulgaris, a chronic, xerotic (abnormally dry), scaly skin disease with an estimated incidence and prevalence of 1 in 250, which suggests a total patient population of 1.3 million in the United States.
We dosed the first patient in the Phase 1/2 clinical trial in the third quarter of 2025. 1 • ATR-01 , a genetically modified strain of S. epidermidis that expresses an engineered recombinant human filaggrin protein for treating ichthyosis vulgaris, a chronic, xerotic (abnormally dry), scaly skin disease with an estimated incidence and prevalence of 1 in 250, which suggests a total patient population of 1.3 million in the United States.
ATR-12 is a topical application intended to address the underlying cause of Netherton syndrome, by replacing deficient LEKTI with an active segment of human recombinant LEKTI, or rhLEKTI-D6, to counter the dysregulated skin serine protease activity observed in Netherton syndrome patients.
ATR-12-351 is a topical formulation containing SE351 intended to address the underlying cause of Netherton syndrome, by replacing deficient LEKTI with an active segment of human recombinant LEKTI, or rhLEKTI-D6, to counter the dysregulated skin serine protease activity observed in Netherton syndrome patients.
We are also aware that Sixera Pharma initiated a clinical trial in Europe with SXR-1096, a topical small molecule KLK inhibitor in December 2021 for Netherton syndrome. In addition, Quoin Pharmaceuticals initiated two clinical trials with QRX003, a topical small molecule broad-spectrum serine protease inhibitor, in December 2022 and March 2023.
We are also aware that Sixera Pharma initiated a clinical trial in Europe with SXR-1096, a topical small molecule KLK inhibitor in December 2021 for Netherton syndrome. In addition, Quoin Pharmaceuticals initiated a pivotal clinical trial with QRX003, a topical small molecule broad-spectrum serine protease inhibitor for Netherton syndrome, in March 2023.
We expect to leverage these partnerships and potentially expand them or form other academic partnerships to bolster our engineering platforms and expand our research and development pipeline. • Experienced management team and Board of Directors . We are led by Francisco D.
We expect to leverage these partnerships and potentially expand them or form other academic partnerships to bolster our engineering platforms and expand our research and development pipeline. • Experienced management team and Board of Directors . We are led by Francisco D. Salva, our chief executive officer, and Dr.
Regulatory Requirements After a Marketing Authorization Has Been Obtained If we obtain authorization for a medicinal product in the EU, we will be required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products: Pharmacovigilance We will, for example, have to comply with the EU’s stringent pharmacovigilance or safety reporting rules, pursuant to which post-authorization studies and additional monitoring obligations can be imposed.
Regulatory Requirements After a Marketing Authorization Has Been Obtained If we obtain authorization for a medicinal product in the EU, we will be required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products: Pharmacovigilance We will, for example, have to comply with the EU’s stringent pharmacovigilance or safety reporting rules, pursuant to which post-authorization studies and additional monitoring obligations can be imposed. 34 Other requirements relate to, for example, the manufacturing of products and APIs in accordance with good manufacturing practice standards.
In December 2022, we filed an IND for a first-in-human trial of ATR-12 in Netherton syndrome patients. Our IND proposes a Phase 1b multi-center, randomized, double-blind, single dose level, placebo-controlled clinical study of ATR-12 in patients with Netherton syndrome. The primary endpoint is safety, and secondary endpoints include signals of efficacy and pharmacokinetics.
In December 2022, we filed an IND for a first-in-human trial of ATR-12 in Netherton syndrome patients. This is a Phase 1b multi-center, randomized, double-blind, single dose level, placebo-controlled clinical study of ATR-12 in patients with Netherton syndrome. The primary endpoint is safety, and secondary endpoints include signals of efficacy and pharmacokinetics. Exploratory endpoints include immune and inflammatory mechanism biomarkers.
Based on studies conducted by Satoh and Lichtenberger, the cytokine, Interleukin-36 gamma, or IL-36γ, and S. aureus are linked to and play a significant role in the rashes experienced by patients treated with EGFRis. IL-36γ, is elevated in the skin of patients undergoing EGFRi therapy.
Based on studies conducted by Satoh and Lichtenberger, IL-36γ and S. aureus are linked to and play a significant role in the rashes experienced by patients treated with EGFRis. IL-36γ and S. aureum are elevated in the skin of patients undergoing EGFRi therapy.
Specifically, the FDA may designate a product for Fast Track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition.
These programs are Fast Track designation, breakthrough therapy designation and priority review designation. 26 Specifically, the FDA may designate a product for Fast Track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet medical needs for such a disease or condition.
Item 1. Business Background Azitra, Inc. was formed as a Delaware corporation on January 2, 2014 for the purpose of developing innovative therapies for precision dermatology using engineered proteins and topical live biotherapeutic products.
Item 1. Business Background Azitra, Inc. was formed as a Delaware corporation on January 2, 2014 as a biopharmaceutical company focused on developing innovative therapies for precision dermatology using engineered proteins and topical live biotherapeutic products.
The main characteristics of the regulation include: • A streamlined application procedure via a single entry point, known as the Clinical Trials Information System; • A single set of documents to be prepared and submitted for the application as well as simplified reporting procedures which will spare sponsors from submitting broadly identical information separately to various and different national authorities; • A harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts; • Strictly defined deadlines for the assessment of clinical trial application; and • The involvement of the ethics committees in the assessment procedure in accordance with the national law of the member state concerned but within the overall timelines defined by the Regulation (EU) No 536/2014.
The main characteristics of the regulation include: • A streamlined application procedure via a single entry point, known as the Clinical Trials Information System; • A single set of documents to be prepared and submitted for the application as well as simplified reporting procedures which will spare sponsors from submitting broadly identical information separately to various and different national authorities; • A harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts; • Strictly defined deadlines for the assessment of clinical trial application; and • The involvement of the ethics committees in the assessment procedure in accordance with the national law of the member state concerned but within the overall timelines defined by the Regulation (EU) No 536/2014. 31 Marketing Authorization Authorization to market a product in the member states of the EU proceeds under one of four procedures: a centralized procedure, a mutual recognition procedure, a decentralized procedure or a national procedure.
Additional regulatory protection may also be afforded through data exclusivity, market exclusivity and patent-term extensions where available. As of the date of this report, we own or exclusively license three issued U.S. patents, 12 pending U.S. patent applications, three pending PCT application and 57 other foreign patents and patent applications that are important to the development of our business.
Additional regulatory protection may also be afforded through data exclusivity, market exclusivity and patent-term extensions where available. As of the date of this report, we own or exclusively license seven issued U.S. patents, two allowed patent applications, 9 pending U.S. patent applications, and 85 other foreign patents and patent applications that are important to the development of our business.
To date, our team has successfully engineered our lead therapeutic candidates without the SyMPL technology. However, we believe that SyMPL will open up the ability to make genetic transformations of an expanded universe of microbial species, and we expect that some or all of our future product candidates will incorporate the SyMPL technology.
However, we believe that SyMPL will open up the ability to make genetic transformations of an expanded universe of microbial species, and we expect that some or all of our future product candidates will incorporate the SyMPL technology.
The program is currently investigating a proprietary and patent-pending novel engineering segment of human filaggrin protein. ATR-01 is being developed as a topical application intended to address ichthyosis vulgaris, a chronic scaly skin disease with an estimated incidence and prevalence of 1 in 250, which gives a total patient population of 1.3 million in the United States.
ATR-01 is being developed as a topical application intended to address ichthyosis vulgaris, a chronic scaly skin disease with an estimated incidence and prevalence of 1 in 250, which gives a total patient population of 1.3 million in the United States.
The uncontrolled serine protease activity leads to a profound skin barrier defect and the release of pro-inflammatory and pro-allergic mediators by keratinocytes and immune cells. To date, there is no known therapy for the cure or effective treatment of Netherton syndrome. We believe ATR-12 has the potential to be the first therapy to effectively treat this disease of the skin.
The uncontrolled serine protease activity leads to a profound skin barrier defect and the release of pro-inflammatory and pro-allergic mediators by keratinocytes and immune cells. To date, there is no known therapy for the cure or effective treatment of Netherton syndrome.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIn January, 2025, we completed a public offering of 4,857,780 shares of our common stock, at an offering price of $0.30 per share, in which we received net proceeds of approximately $1.3 million, after deducting underwriter discounts and offering expenses, and February 2025 we completed a registered direct offering of 2,495,518 shares of our common stock, at an offering price of $0.2785 per share, in which we received net proceeds of approximately $695 thousand, after deducting placement agent commissions and offering expenses.
Biggest changeIn January, 2025, we completed a public offering of 729,381 shares of our common stock, at an offering price of $2.00 per share, in which we received net proceeds of approximately $1.2 million, after deducting underwriter discounts and offering expenses, in February 2025 we completed a registered direct offering of 374,696 shares of our common stock, at an offering price of $1.85 per share, in which we received net proceeds of approximately $695 thousand, 40 after deducting placement agent commissions and offering expenses; in April 2025 we entered into an equity line of credit with Alumni Capital LP pursuant to which we have sold 9,255,823 shares and received gross proceeds of approximately $6 million; and in November 2025 we completed an offering of 535,759 shares at an offering price of $0.32, pre-funded warrants to purchase up to an aggregate of 4,151,741 shares and warrants to purchase up to an aggregate 4,687,500 shares, in which we received net proceeds of approximately, $1.3 million, after deducting underwriter discounts and offering expenses.
The commencement and completion of clinical studies can be delayed for a number of reasons, including delays related to: • the FDA or a comparable foreign regulatory authority failing to grant permission to proceed and placing the clinical study on hold; • subjects for clinical testing failing to enroll or remain enrolled in our trials at the rate we expect; • a facility manufacturing any of our product candidates being ordered by the FDA or other government or regulatory authorities to temporarily or permanently shut down due to violations of cGMP requirements or other applicable requirements, or cross-contaminations of product candidates in the manufacturing process; • any changes to our manufacturing process that may be necessary or desired; • subjects choosing an alternative treatment for the indications for which we are developing our product candidates, or participating in competing clinical studies; • subjects experiencing severe or unexpected drug-related adverse effects; • reports from clinical testing on similar technologies and products raising safety and/or efficacy concerns; • third-party clinical investigators losing their license or permits necessary to perform our clinical trials, not performing our clinical trials on our anticipated schedule or employing methods consistent with the clinical trial protocol, cGMP requirements, or other third parties not performing data collection and analysis in a timely or accurate manner; • inspections of clinical study sites by the FDA, comparable foreign regulatory authorities, or IRBs finding regulatory violations that require us to undertake corrective action, result in suspension or termination of one or more sites or the imposition of a clinical hold on the entire study, or that prohibit us from using some or all of the data in support of our marketing applications; • third-party contractors becoming debarred or suspended or otherwise penalized by the FDA or other government or regulatory authorities for violations of regulatory requirements, in which case we may need to find a substitute contractor, and we may not be able to use some or any of the data produced by such contractors in support of our marketing applications; • one or more IRBs refusing to approve, suspending or terminating the study at an investigational site, precluding enrollment of additional subjects, or withdrawing its approval of the trial; reaching agreement on acceptable terms with prospective contract research organizations, or 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; • deviations of the clinical sites from trial protocols or dropping out of a trial; 50 • adding new clinical trial sites; • the inability of the CRO to execute any clinical trials for any reason; and • government or regulatory delays or “clinical holds” requiring suspension or termination of a trial.
The commencement and completion of clinical studies can be delayed for a number of reasons, including delays related to: • the FDA or a comparable foreign regulatory authority failing to grant permission to proceed and placing the clinical study on hold; • subjects for clinical testing failing to enroll or remain enrolled in our trials at the rate we expect; • a facility manufacturing any of our product candidates being ordered by the FDA or other government or regulatory authorities to temporarily or permanently shut down due to violations of cGMP requirements or other applicable requirements, or cross-contaminations of product candidates in the manufacturing process; • any changes to our manufacturing process that may be necessary or desired; • subjects choosing an alternative treatment for the indications for which we are developing our product candidates, or participating in competing clinical studies; • subjects experiencing severe or unexpected drug-related adverse effects; • reports from clinical testing on similar technologies and products raising safety and/or efficacy concerns; • third-party clinical investigators losing their license or permits necessary to perform our clinical trials, not performing our clinical trials on our anticipated schedule or employing methods consistent with the clinical trial protocol, cGMP requirements, or other third parties not performing data collection and analysis in a timely or accurate manner; • inspections of clinical study sites by the FDA, comparable foreign regulatory authorities, or IRBs finding regulatory violations that require us to undertake corrective action, result in suspension or termination of one or more sites or the imposition of a clinical hold on the entire study, or that prohibit us from using some or all of the data in support of our marketing applications; • third-party contractors becoming debarred or suspended or otherwise penalized by the FDA or other government or regulatory authorities for violations of regulatory requirements, in which case we may 50 need to find a substitute contractor, and we may not be able to use some or any of the data produced by such contractors in support of our marketing applications; • one or more IRBs refusing to approve, suspending or terminating the study at an investigational site, precluding enrollment of additional subjects, or withdrawing its approval of the trial; reaching agreement on acceptable terms with prospective contract research organizations, or 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; • deviations of the clinical sites from trial protocols or dropping out of a trial; • adding new clinical trial sites; • the inability of the CRO to execute any clinical trials for any reason; and • government or regulatory delays or “clinical holds” requiring suspension or termination of a trial.
The FDA has the authority to require a REMS as part of an BLA or after approval, which may impose further requirements or restrictions on the distribution or use of an approved drug, such as limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria or requiring patient testing, monitoring and/or enrollment in a registry.
The FDA has the authority to require a REMS as part of a BLA or after approval, which may impose further requirements or restrictions on the distribution or use of an approved drug, such as limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria or requiring patient testing, monitoring and/or enrollment in a registry.
The market price of our shares on the NYSE American may fluctuate as a result of a number of factors, some of which are beyond our control, including, but not limited to: • actual or anticipated variations in our and our competitors’ results of operations and financial condition; • changes in earnings estimates or recommendations by securities analysts, if our shares are covered by analysts; • market acceptance of our product candidates; • development of technological innovations or new competitive products by others; • announcements of technological innovations or new products by us; • publication of the results of preclinical or clinical trials for our product candidates; • failure by us to achieve a publicly announced milestone; • delays between our expenditures to develop and market new or enhanced products and the generation of sales from those products; • developments concerning intellectual property rights, including our involvement in litigation brought by or against us; • regulatory developments and the decisions of regulatory authorities as to the approval or rejection of new or modified products; • changes in the amounts that we spend to develop, acquire or license new products, technologies or businesses; • changes in our expenditures to promote our product candidates; • our sale or proposed sale, or the sale by our significant stockholders, of our shares or other securities in the future; • changes in key personnel; • success or failure of our research and development projects or those of our competitors; • the trading volume of our shares; and • general economic and market conditions and other factors, including factors unrelated to our operating performance.
The market price of our shares on the NYSE American may fluctuate as a result of a number of factors, some of which are beyond our control, including, but not limited to: • actual or anticipated variations in our and our competitors’ results of operations and financial condition; • changes in earnings estimates or recommendations by securities analysts, if our shares are covered by analysts; • market acceptance of our product candidates; • development of technological innovations or new competitive products by others; • announcements of technological innovations or new products by us; • publication of the results of preclinical or clinical trials for our product candidates; • failure by us to achieve a publicly announced milestone; • delays between our expenditures to develop and market new or enhanced products and the generation of sales from those products; • developments concerning intellectual property rights, including our involvement in litigation brought by or against us; 61 • regulatory developments and the decisions of regulatory authorities as to the approval or rejection of new or modified products; • changes in the amounts that we spend to develop, acquire or license new products, technologies or businesses; • changes in our expenditures to promote our product candidates; • our sale or proposed sale, or the sale by our significant stockholders, of our shares or other securities in the future; • changes in key personnel; • success or failure of our research and development projects or those of our competitors; • the trading volume of our shares; and • general economic and market conditions and other factors, including factors unrelated to our operating performance.
The degree of market acceptance for any of our product candidates will depend on a number of factors, including: • demonstration of clinical safety and efficacy; • relative convenience, dosing burden and ease of administration; • the prevalence and severity of any adverse effects; • the willingness of physicians to prescribe our product candidates, and the target patient population to try new therapies; • efficacy of our product candidates compared to competing products; • the introduction of any new products that may in the future become available targeting indications for which our product candidates may be approved; • new procedures or therapies that may reduce the incidences of any of the indications in which our product candidates may show utility; • pricing and cost-effectiveness; • the inclusion or omission of our product candidates in applicable therapeutic and vaccine guidelines; • the effectiveness of our own or any future collaborators’ sales and marketing strategies; • limitations or warnings contained in approved labeling from regulatory authorities; • our ability to obtain and maintain sufficient third-party coverage or reimbursement from government health care programs, including Medicare and Medicaid, private health insurers and other third-party payors or to receive the necessary pricing approvals from government bodies regulating the pricing and usage of therapeutics; and • the willingness of patients to pay out-of-pocket in the absence of third-party coverage or reimbursement or government pricing approvals.
The degree of market acceptance for any of our product candidates will depend on a number of factors, including: • demonstration of clinical safety and efficacy; • relative convenience, dosing burden and ease of administration; • the prevalence and severity of any adverse effects; • the willingness of physicians to prescribe our product candidates, and the target patient population to try new therapies; • efficacy of our product candidates compared to competing products; • the introduction of any new products that may in the future become available targeting indications for which our product candidates may be approved; • new procedures or therapies that may reduce the incidences of any of the indications in which our product candidates may show utility; • pricing and cost-effectiveness; • the inclusion or omission of our product candidates in applicable therapeutic and vaccine guidelines; • the effectiveness of our own or any future collaborators’ sales and marketing strategies; • limitations or warnings contained in approved labeling from regulatory authorities; • our ability to obtain and maintain sufficient third-party coverage or reimbursement from government health care programs, including Medicare and Medicaid, private health insurers and other third-party 51 payors or to receive the necessary pricing approvals from government bodies regulating the pricing and usage of therapeutics; and • the willingness of patients to pay out-of-pocket in the absence of third-party coverage or reimbursement or government pricing approvals.
All such reported information is publicly available; • analogous state and non-U.S. laws and regulations, such as certain state anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and • regulation by CMS and enforcement by the HHS Office of Inspector General or the U.S.
All such reported information is publicly available; • analogous state and non-U.S. laws and regulations, such as certain state anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the industry’s voluntary compliance guidelines and the applicable compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral 58 sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and • regulation by CMS and enforcement by the HHS Office of Inspector General or the U.S.
In addition, the government may assert that a claim including items or services resulting from a violation 57 of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act; • the federal False Claims Act imposes civil penalties, and provides for civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; • the Health Insurance Portability and Accountability Act, or HIPAA imposes criminal and civil liability for executing a scheme to defraud any health care benefit program or making false statements relating to health care matters.
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 False Claims Act; • the federal False Claims Act imposes civil penalties, and provides for civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; • the Health Insurance Portability and Accountability Act, or HIPAA imposes criminal and civil liability for executing a scheme to defraud any health care benefit program or making false statements relating to health care matters.
Increasingly, third-party payors attempt to contain health care costs in ways that are likely to impact our development of products including: • failing to approve or challenging the prices charged for health care products; • introducing reimportation schemes from lower priced jurisdictions; • limiting both coverage and the amount of reimbursement for new therapeutic products; • denying or limiting coverage for products that are approved by the regulatory agencies but are considered to be experimental or investigational by third-party payors; and • refusing to provide coverage when an approved product is used in a way that has not received regulatory marketing approval.
Increasingly, third-party payors attempt to contain health care costs in ways that are likely to impact our development of products including: • failing to approve or challenging the prices charged for health care products; • introducing reimportation schemes from lower priced jurisdictions; 57 • limiting both coverage and the amount of reimbursement for new therapeutic products; • denying or limiting coverage for products that are approved by the regulatory agencies but are considered to be experimental or investigational by third-party payors; and • refusing to provide coverage when an approved product is used in a way that has not received regulatory marketing approval.
In addition, there can be no assurance that our internal information technology systems or those of our third-party contractors, or our consultants’ efforts to implement adequate security and control measures, will be sufficient to protect us against breakdowns, service disruption, data deterioration or loss in the event of a system malfunction, or prevent data from being stolen or corrupted in the event of a cyberattack, security breach, industrial espionage attacks or insider threat attacks which could result in financial, legal, business or reputational harm.
In addition, there can be no assurance that our internal information technology systems or those of our third-party contractors, or our consultants’ efforts to implement adequate security and control measures, will be sufficient to protect us against breakdowns, service disruption, data deterioration or loss in the event of a system malfunction, or prevent data from being stolen or corrupted in the event of a cyberattack, security breach, 46 industrial espionage attacks or insider threat attacks which could result in financial, legal, business or reputational harm.
If these manufacturers or any alternate manufacturer of finished drug product experiences any significant difficulties in its respective 44 manufacturing processes for our required raw materials, manufacturing devices, active pharmaceutical ingredients or finished product or should cease doing business with us for any reason, we could experience significant delays in our clinical trials and significant interruptions in the supply of any of our product candidates or may not be able to create a supply of our product candidates at all.
If these manufacturers or any alternate manufacturer of finished drug product experiences any significant difficulties in its respective manufacturing processes for our required raw materials, manufacturing devices, active pharmaceutical ingredients or finished product or should cease doing business with us for any reason, we could experience significant delays in our clinical trials and significant interruptions in the supply of any of our product candidates or may not be able to create a supply of our product candidates at all.
In the event of a delisting, we can provide no assurance that any action taken by us to restore compliance with listing requirements would allow 61 our common stock to become listed again, stabilize the market price or improve the liquidity of our common stock, prevent our common stock from dropping below the NYSE American’s minimum bid price requirement or prevent future non-compliance with the NYSE American’s listing requirements.
In the event of a delisting, we can provide no assurance that any action taken by us to restore compliance with listing requirements would allow our common stock to become listed again, stabilize the market price or improve the liquidity of our common stock, prevent our common stock from dropping below the NYSE American’s minimum bid price requirement or prevent future non-compliance with the NYSE American’s listing requirements.
Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient 56 reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
If government spending is further reduced, anticipated budgetary shortfalls may also impact the ability of relevant agencies, such as the FDA, to 55 continue to function at current levels, which may impact the ability of relevant agencies to timely review and approve research and development, manufacturing and marketing activities, which may delay our ability to develop, market and sell any product candidates we may develop.
If government spending is further reduced, anticipated budgetary shortfalls may also impact the ability of relevant agencies, such as the FDA, to continue to function at current levels, which may impact the ability of relevant agencies to timely review and approve research and development, manufacturing and marketing activities, which may delay our ability to develop, market and sell any product candidates we may develop.
Until such time, if ever, as we are able to provide the FDA with substantial clinical evidence to support a claim of safety, efficacy, purity and potency sufficient to enable the FDA to approve our 41 proprietary product candidates for any indication, our proprietary microbial library and genetic engineering platform will remain unproven.
Until such time, if ever, as we are able to provide the FDA with substantial clinical evidence to support a claim of safety, efficacy, purity and potency sufficient to enable the FDA to approve our proprietary product candidates for any indication, our proprietary microbial library and genetic engineering platform will remain unproven.
Before an IND can be submitted to the FDA and become effective, which is a prerequisite for conducting clinical trials on human subjects in the United States, a product candidate must successfully progress through extensive preclinical studies, which include preclinical laboratory testing, animal studies, and formulation studies in accordance with Good Laboratory Practices.
Before an IND can be submitted to the FDA and become effective, which is a prerequisite for 49 conducting clinical trials on human subjects in the United States, a product candidate must successfully progress through extensive preclinical studies, which include preclinical laboratory testing, animal studies, and formulation studies in accordance with Good Laboratory Practices.
If we raise additional funds through collaborations and licensing arrangements, we may be required to relinquish some rights to our intellectual property or candidate products, or to grant licenses on terms that are not favorable to us. Shares eligible for future sale may adversely affect the market for our common stock .
If we raise 62 additional funds through collaborations and licensing arrangements, we may be required to relinquish some rights to our intellectual property or candidate products, or to grant licenses on terms that are not favorable to us. Shares eligible for future sale may adversely affect the market for our common stock .
Accordingly, you should consider our prospects in light of the costs, uncertainties, delays and difficulties frequently encountered by companies in the early stages of development, especially early-stage clinical-stage biopharmaceutical companies such as ours. Potential investors should carefully consider the risks and uncertainties that a company with a limited operating history will face.
Accordingly, you should consider our prospects in light of the costs, uncertainties, delays and difficulties frequently encountered by companies in the early stages of development, especially early-stage clinical-stage biopharmaceutical companies such as ours. Potential investors 39 should carefully consider the risks and uncertainties that a company with a limited operating history will face.
Success in preclinical studies and earlier clinical trials does not ensure that later efficacy trials will be successful, nor does it predict final results. Our product candidates may fail to show the desired safety and efficacy in clinical development despite positive results in preclinical studies or even if they successfully advance through earlier clinical trials.
Success in preclinical studies and earlier clinical trials does not ensure that later efficacy trials will be successful, nor does it predict final results. Our product candidates 41 may fail to show the desired safety and efficacy in clinical development despite positive results in preclinical studies or even if they successfully advance through earlier clinical trials.
Our product candidates may infringe the intellectual property rights of others, which could increase our costs and delay or prevent our development and commercialization efforts. Our success depends in part on avoiding infringement of the proprietary technologies of others. The pharmaceutical industry has been characterized by frequent litigation regarding patent and other intellectual property 59 rights.
Our product candidates may infringe the intellectual property rights of others, which could increase our costs and delay or prevent our development and commercialization efforts. Our success depends in part on avoiding infringement of the proprietary technologies of others. The pharmaceutical industry has been characterized by frequent litigation regarding patent and other intellectual property rights.
We cannot predict whether we would prevail in any such actions or that any license required under any of these patents would be made available on commercially acceptable terms, if at all. In addition, we cannot be sure that we could redesign our product candidates or any future product candidates or processes to avoid infringement, if necessary.
We cannot predict whether we would prevail in any such actions or that any license required under any of these patents would be made available on commercially acceptable terms, if at all. In addition, we cannot be sure that we could redesign our product candidates or any future product candidates or processes to avoid 60 infringement, if necessary.
The number and complexity of these threats continue to increase over time. If a material breach of, or accidental or intentional loss of data from, our information technology systems or 46 those of our vendors occurs, the market perception of the effectiveness of our security measures could be harmed and our reputation and credibility could be damaged.
The number and complexity of these threats continue to increase over time. If a material breach of, or accidental or intentional loss of data from, our information technology systems or those of our vendors occurs, the market perception of the effectiveness of our security measures could be harmed and our reputation and credibility could be damaged.
Risks Relating to Our Intellectual Property Rights It is difficult and costly to protect our intellectual property rights, and we cannot ensure the protection of these rights. 58 Our commercial success will depend, in part, on our ability to prosecute and defend, if necessary, our patent rights against third-party challenges and successfully enforcing these patent rights against third party competitors.
Risks Relating to Our Intellectual Property Rights It is difficult and costly to protect our intellectual property rights, and we cannot ensure the protection of these rights. Our commercial success will depend, in part, on our ability to prosecute and defend, if necessary, our patent rights against third-party challenges and successfully enforcing these patent rights against third party competitors.
Investors may be unable to compare our business with other companies in our industry if they believe 62 that our reporting is not as transparent as other companies in our industry. If we are unable to raise additional capital as and when we need it, our financial condition and results of operations may be materially and adversely affected.
Investors may be unable to compare our business with other companies in our industry if they believe that our reporting is not as transparent as other companies in our industry. If we are unable to raise additional capital as and when we need it, our financial condition and results of operations may be materially and adversely affected.
Our future financial performance and our ability to commercialize our product candidates and any other future product candidates and our ability to compete effectively will depend, in part, on our ability to effectively manage our future growth. 42 If we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy.
Our future financial performance and our ability to commercialize our product candidates and any other future product candidates and our ability to compete effectively will depend, in part, on our ability to effectively manage our future growth. If we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy.
Any such product liability claims may include allegations of defects in 45 manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. In the U.S., claims could also be asserted against us under state consumer protection acts.
Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. In the U.S., claims could also be asserted against us under state consumer protection acts.
Approval procedures vary among jurisdictions and can involve requirements 53 and administrative review periods different from those in the United States, including additional preclinical studies or clinical trials, as clinical studies conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions.
Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from those in the United States, including additional preclinical studies or clinical trials, as clinical studies conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions.
Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management. 60 Risks Related to Owning Our Common Stock The market price of our shares may be subject to fluctuation and volatility.
Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management. Risks Related to Owning Our Common Stock The market price of our shares may be subject to fluctuation and volatility.
Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation. Such mechanisms include re-examination, post grant review and equivalent proceedings in foreign jurisdictions, e.g., opposition proceedings.
Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside 59 the context of litigation. Such mechanisms include re-examination, post grant review and equivalent proceedings in foreign jurisdictions, e.g., opposition proceedings.
We do not plan to pay any cash dividends with respect to our common stock in the foreseeable future. We cannot assure you that we would, at any time, generate sufficient surplus cash that would be available for distribution to the holders of our common stock as a dividend.
We do not plan to pay any cash dividends with respect to our common stock in the foreseeable future. We cannot assure you that we would, at any time, generate sufficient surplus cash 63 that would be available for distribution to the holders of our common stock as a dividend.
As a result, it may be more difficult for us to attract and retain qualified people to serve on our Board our Board committees or as executive officers. 65 Unfavorable geopolitical and macroeconomic developments could adversely affect our business, financial condition or results of operations.
As a result, it may be more difficult for us to attract and retain qualified people to serve on our Board our Board committees or as executive officers. Unfavorable geopolitical and macroeconomic developments could adversely affect our business, financial condition or results of operations.
National governments and health service providers have different priorities and approaches to the delivery of health care and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU member states have resulted in restrictions on the pricing and 56 reimbursement of medicines by relevant health service providers.
National governments and health service providers have different priorities and approaches to the delivery of health care and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU member states have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers.
These provisions may have the effect of 63 entrenching our management team and may deprive you of the opportunity to sell your shares to potential acquirers at a premium over prevailing prices. This potential inability to obtain a control premium could reduce the price of our common stock.
These provisions may have the effect of entrenching our management team and may deprive you of the opportunity to sell your shares to potential acquirers at a premium over prevailing prices. This potential inability to obtain a control premium could reduce the price of our common stock.
If any of our product candidates are approved, but do not achieve an adequate level of acceptance by physicians, health care payors, and patients, we may not generate sufficient revenue and we may not be able to 51 achieve or sustain profitability.
If any of our product candidates are approved, but do not achieve an adequate level of acceptance by physicians, health care payors, and patients, we may not generate sufficient revenue and we may not be able to achieve or sustain profitability.
Under the FDA’s rare pediatric disease priority review voucher, or RPD‑PRV, program, upon the approval of an NDA or BLA for the treatment of a rare pediatric disease, the sponsor of such application would be eligible for an RPD‑PRV that can be used to obtain priority review for a subsequent NDA or BLA.
Under the FDA’s rare 54 pediatric disease priority review voucher, or RPD‑PRV, program, upon the approval of an NDA or BLA for the treatment of a rare pediatric disease, the sponsor of such application would be eligible for an RPD‑PRV that can be used to obtain priority review for a subsequent NDA or BLA.
Any such deficiencies, weaknesses or lack of compliance could have a materially adverse effect on our ability to comply with the reporting requirements of the Securities Exchange Act of 1934, or the Exchange Act, which is necessary to maintain our public company 64 status.
Any such deficiencies, weaknesses or lack of compliance could have a materially adverse effect on our ability to comply with the reporting requirements of the Securities Exchange Act of 1934, or the Exchange Act, which is necessary to maintain our public company status.
If we are unable to continue to attract and retain high-quality personnel, the rate and success at which we can develop and commercialize product candidates would be limited. We currently have no sales and marketing organization.
If we are unable to continue to attract and retain 42 high-quality personnel, the rate and success at which we can develop and commercialize product candidates would be limited. We currently have no sales and marketing organization.
We expect to continue to 40 incur substantial expenses without any meaningful revenues unless and until we are able to obtain regulatory approval and successfully commercialize at least one of our product candidates.
We expect to continue to incur substantial expenses without any meaningful revenues unless and until we are able to obtain regulatory approval and successfully commercialize at least one of our product candidates.
These setbacks have been caused by, among other things, preclinical findings made while clinical trials were underway and safety or efficacy observations made in clinical trials, including previously unreported 49 adverse events.
These setbacks have been caused by, among other things, preclinical findings made while clinical trials were underway and safety or efficacy observations made in clinical trials, including previously unreported adverse events.
Our success depends on our receipt of the regulatory approvals described above, and the issuance of such regulatory approvals is uncertain and subject to a number of risks, including the following: • such authorities may disagree with the number, design, size, conduct or implementation of our clinical trials or any of our collaborators’ clinical trials; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials or the use of results from studies that served as precursors to our current or future product candidates; 47 • the results of toxicology studies may not support the filing of an Investigational New Drug Application, or IND, or a BLA for our product candidates; • the FDA or comparable foreign regulatory authorities or Institutional Review Boards, or IRBs, may disagree with the design or implementation of our clinical trials; • we may not be able to provide acceptable evidence of our product candidates’ safety and efficacy; • the results of our clinical trials may not be satisfactory or may not meet the level of statistical or clinical significance required by the FDA, European Medicines Agency, or EMA, or other regulatory agencies for us to receive marketing approval for any of our product candidates; • the dosing of our product candidates in a particular clinical trial may not be at an optimal level; • patients in our clinical trials may suffer adverse effects for reasons that may or may not be related to our product candidates; • the data collected from clinical trials may not be sufficient to support the submission of a BLA or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA may require development of a Risk Evaluation and Mitigation Strategy, or REMS, as a condition of approval; • the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval of our product candidates.
As of the date of this report, we have not submitted a BLA to the FDA or comparable applications to other regulatory authorities for any of our product candidates. 47 Our success depends on our receipt of the regulatory approvals described above, and the issuance of such regulatory approvals is uncertain and subject to a number of risks, including the following: • such authorities may disagree with the number, design, size, conduct or implementation of our clinical trials or any of our collaborators’ clinical trials; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials or the use of results from studies that served as precursors to our current or future product candidates; • the results of toxicology studies may not support the filing of an Investigational New Drug Application, or IND, or a BLA for our product candidates; • the FDA or comparable foreign regulatory authorities or Institutional Review Boards, or IRBs, may disagree with the design or implementation of our clinical trials; • we may not be able to provide acceptable evidence of our product candidates’ safety and efficacy; • the results of our clinical trials may not be satisfactory or may not meet the level of statistical or clinical significance required by the FDA, European Medicines Agency, or EMA, or other regulatory agencies for us to receive marketing approval for any of our product candidates; • the dosing of our product candidates in a particular clinical trial may not be at an optimal level; • patients in our clinical trials may suffer adverse effects for reasons that may or may not be related to our product candidates; • the data collected from clinical trials may not be sufficient to support the submission of a BLA or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA may require development of a Risk Evaluation and Mitigation Strategy, or REMS, as a condition of approval; • the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval of our product candidates.
Orphan drug designation must be requested before submitting an BLA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan product designation does not convey any advantage in or shorten the duration of regulatory review and approval process.
Orphan drug designation must be requested before submitting a BLA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan product designation does not convey any advantage in or shorten the duration of regulatory review and approval process.
The report of our independent registered public accounting firm for the year ended December 31, 2024 states that due to our accumulated deficit, recurring and negative cash flow from operations there is substantial doubt about our ability to continue as a going concern.
The report of our independent registered public accounting firm for the year ended December 31, 2025 states that due to our accumulated deficit, recurring and negative cash flow from operations there is substantial doubt about our ability to continue as a going concern.
Our business model includes the potential out-licensing of strains from our proprietary microbial library or our product candidates to other biopharmaceutical companies, however technology licensing in the biopharmaceutical industry is a lengthy process and subject to several risks and factors outside of our control, and we cannot forecast our ability to successfully out-license our technology or the length of time it takes to establish a new licensing relationship.
Our business model includes the potential out-licensing of strains from our proprietary microbial library or our product candidates to other biopharmaceutical companies, however technology licensing in the biopharmaceutical industry is a lengthy process and subject to several risks and factors outside of our control, and we cannot forecast our ability to successfully out-license our technology or the length of time it takes to establish a new licensing relationship. 44 Our business model includes the potential out-licensing or joint development of strains from our proprietary microbial library or our product candidates to other biopharmaceutical companies.
With the change in presidential administrations in 2025, there is substantial uncertainty as to how, if at all, the new administration will seek to modify or revise the requirements and policies of the FDA and other regulatory agencies with jurisdiction over our product candidates.
With the change in presidential administrations in 2025, there remains substantial uncertainty as to how, if at all, the administration will seek to modify or revise the requirements and policies of the FDA and other regulatory agencies with jurisdiction over our product candidates.
After giving effect to both offerings, we believe that our cash on hand as of the date of this report will not be sufficient to cover our proposed plan of operations beyond six months from the date of this report.
After giving effect to these offerings, we believe that our cash on hand as of the date of this report will not be sufficient to cover our proposed plan of operations beyond three months from the date of this report.
We recently initiated our Phase 1b clinical trial for ATR-12 and dosed our first patient in August 2024 and expect to dose the first patient in the Phase 1/2 trial of ATR-04 in the first half of 2025. However, success in early clinical trials does not ensure that large-scale clinical trials will be successful, nor does it predict final results.
We recently initiated our Phase 1b clinical trial for ATR-12 and dosed our first patient in August 2024 and dosed the first patient in the Phase 1/2 trial of ATR-04 in the third quarter of 2025. However, success in early clinical trials does not ensure that large-scale clinical trials will be successful, nor does it predict final results.
If we fail to satisfy the continued listing requirements of the NYSE American, such as the corporate governance requirements or the minimum closing bid price requirement, the NYSE American may take steps to delist our common stock.
Additionally, if we fail to satisfy the continued listing requirements of the NYSE American, including the corporate governance requirements or the minimum closing bid price requirement, the NYSE American may take steps to delist our common stock.
As of the date of this report, we have 12,483,836 shares of common stock issued and outstanding, all of which are eligible for sale by means of ordinary brokerage transactions in the open market pursuant to Rule 144, promulgated under the Securities Act, subject to certain limitations under Rule 144.
As of the date of this report, we have 16,192,438 shares of common stock issued and outstanding, all of which are eligible for sale by means of ordinary brokerage transactions in the open market pursuant to Rule 144, promulgated under the Securities Act, subject to certain limitations under Rule 144.
Because our product candidates are in early stages clinical trials or of preclinical development, they will require extensive preclinical and clinical testing. We dosed the first patient in our Phase 1b clinical trial for ATR-12 in August 2024,and we expect to dose the first patient in our Phase 1/2 clinical trial for ATR-04 in the first half of 2025.
Because our product candidates are in early stages clinical trials or of preclinical development, they will require extensive preclinical and clinical testing. We dosed the first patient in our Phase 1b clinical trial for ATR-12 in August 2024,and we dosed the first patient in our Phase 1/2 clinical trial for ATR-04 in the third quarter of 2025.
MOCRA will require a cosmetic manufacturer or importer to: ensure that it has on hand substantiation of the safety of its products and ingredients; meet increased registration, record-keeping and reporting requirements; include fragrance and allergen information on its labeling; and be prepared to meet FDA’s to be promulgated good manufacturing practices requirements. These additional requirements may impact budgets and timelines.
MOCRA will require a cosmetic manufacturer or importer to: ensure that it has on hand substantiation of the safety of its products and ingredients; meet increased registration, record-keeping and reporting requirements; include fragrance and allergen information on its labeling; and be prepared to meet FDA’s to be 48 promulgated good manufacturing practices requirements.
Federal Reserve has raised, and may again raise, interest rates, which, coupled with reduced government spending and volatility in financial markets, may have the effect of further increasing economic uncertainty and heightening these risks.
In response to rising inflation, the U.S. Federal Reserve has raised, and may again raise, interest rates, which, coupled with reduced government spending and volatility in financial markets, may have the effect of further increasing economic uncertainty and heightening these risks.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for any of our product candidates or any future products that we may develop; • injury to our reputation; • failure to obtain regulatory approval for our product candidates; • withdrawal of participants in our clinical trials; • costs associated with our defense of the related litigation; • a diversion of our management’s time and our resources; • substantial monetary awards to trial participants or patients; • product recalls, withdrawals or labeling, marketing or promotional restrictions; • the inability to commercialize some or all of our product candidates; and • a decline in the value of our stock.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for any of our product candidates or any future products that we may develop; • injury to our reputation; • failure to obtain regulatory approval for our product candidates; • withdrawal of participants in our clinical trials; • costs associated with our defense of the related litigation; • a diversion of our management’s time and our resources; • substantial monetary awards to trial participants or patients; • product recalls, withdrawals or labeling, marketing or promotional restrictions; • the inability to commercialize some or all of our product candidates; and • a decline in the value of our stock. 45 As of the date of this report, we carry product liability insurance that we consider adequate for our current level of clinical testing and development.
We expect we will need additional financing to execute our business plan and fund operations, which additional financing may not be available on reasonable terms or at all. As of December 31, 2024, we had total assets of $7.4 million and working capital of $3.9 million.
We expect we will need additional financing to execute our business plan and fund operations, which additional financing may not be available on reasonable terms or at all. As of December 31, 2025, we had total assets of $5.0 million and working capital of $2.0 million.
If we are found to have promoted such off-label uses, we may become subject to significant liability and government fines. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant sanctions.
The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant sanctions.
For the fiscal years ended December 31, 2024 and 2023, we incurred a net loss of $9.0 million and $11.3, respectively. As of December 31, 2024, we had an accumulated deficit of $57.6 million.
For the fiscal years ended December 31, 2025 and 2024, we incurred a net loss of $11.0 million and $9.0, respectively. As of December 31, 2025, we had an accumulated deficit of $68.5 million.
Congress has extended the RPD‑PRV program until December 20, 2024, with potential for vouchers to be granted until 2026. This program has been subject to criticism, including by the FDA. As such it is possible that even if we have obtained qualification for an RPD‑PRV, the program may no longer be in effect at the time of approval.
This program has been subject to criticism, including by the FDA. As such it is possible that even if we have obtained qualification for an RPD‑PRV, the program may no longer be in effect at the time of approval.
Accounting principles generally accepted in the United States and related accounting pronouncements, implementation guidelines, and interpretations we apply to a wide range of matters that are relevant to our business, such as accounting for long-lived asset impairment and share-based compensation, are complex and involve subjective assumptions, estimates and judgments by our management.
General Risk Factors Changes in accounting standards and subjective assumptions, estimates and judgments by management related to complex accounting matters may materially impact reporting of our financial condition and results of operations. 64 Accounting principles generally accepted in the United States and related accounting pronouncements, implementation guidelines, and interpretations we apply to a wide range of matters that are relevant to our business, such as accounting for long-lived asset impairment and share-based compensation, are complex and involve subjective assumptions, estimates and judgments by our management.
We intend to increase staffing within our accounting infrastructure sufficient to facilitate proper segregation of accounting functions.
We intend to increase staffing within our accounting infrastructure, and implement additional review controls sufficient to facilitate proper segregation of accounting functions.
The Budget Control Act resulted in the imposition of 2% reductions in Medicare payments to providers beginning in 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2027 absent additional congressional action.
Congress enacted the Budget Control Act of 2011, or the Budget Control Act, which included provisions intended to reduce the federal deficit. The Budget Control Act resulted in the imposition of 2% reductions in Medicare payments to providers beginning in 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2027 absent additional congressional action.
Our inability to obtain and retain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of products we develop.
However, we will need additional product liability coverage at the time we commence commercial sale of our initial product. Our inability to obtain and retain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of products we develop.
Since shares of our common stock were sold in our initial public offering, or IPO, in June 2023 at a price of $150.00 per share, the reported high and low sales prices of our common stock have ranged from $5.18 to $0.20 through February 24, 2025.
Since shares of our common stock were sold in our initial public offering, or IPO, in June 2023 at a price of $999.00 per share, the reported high and low sales prices of our common stock have ranged from $1,034.96 to $0.17 through February 26, 2026.
If we or any future marketing collaborators or contract manufacturers are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies or are not able to maintain regulatory compliance, it could delay or prevent the promotion, marketing or sale of our products, which would adversely affect our business and results of operations.
If we or any future marketing collaborators or contract manufacturers are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies or are not able to maintain regulatory compliance, it could delay or prevent the promotion, marketing or sale of our products, which would adversely affect our business and results of operations. 53 Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in other jurisdictions.
Also, although priority review vouchers may be sold or transferred to third parties, there is no guaranty that we will be able to 54 realize any value if we obtained, and subsequently were able to sell a priority review voucher. The RPD-PRV program is currently scheduled to sunset as of September 30, 2026.
Also, although priority review vouchers may be sold or transferred to third parties, there is no guaranty that we will be able to realize any value if we obtained, and subsequently were able to sell a priority review voucher.
The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program. It is unclear how such challenges, and the healthcare reform measures of the Biden administration will impact the ACA and our business.
The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.
Disruptions at the FDA and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire, retain, or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved, or commercialized in a timely manner or at all, which could negatively impact our business. 48 The ability of the FDA and other government agencies to review and approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory, and policy changes, a government agency’s ability to hire and retain key personnel and accept the payment of user fees, and other events that may otherwise affect the government agency’s ability to perform routine functions.
Disruptions at the FDA and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire, retain, or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved, or commercialized in a timely manner or at all, which could negatively impact our business.
If we were involved in securities litigation, it could impose a substantial cost upon us and divert the resources and attention of our management from our business. Our failure to meet the continued listing requirements of the NYSE American could result in a delisting of our common stock.
If we were involved in securities litigation, it could impose a substantial cost upon us and divert the resources and attention of our management from our business. Our charter limits our ability to issue shares.
Factors that may inhibit our efforts to build an internal sales organization or enter into collaboration arrangements with third parties 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 physicians to prescribe any of our product candidates; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and • unforeseen costs and expenses associated with creating an internal sales and marketing organization. 43 We will be completely dependent for the foreseeable future on third parties to manufacture our product candidates for commercial sale, and the commercialization of our product candidates could be halted, delayed or made less profitable if those third parties fail to obtain manufacturing approval from the FDA or comparable foreign regulatory authorities, fail to provide us with sufficient quantities of our product candidates or fail to do so at acceptable quality levels or prices .
Factors that may inhibit our efforts to build an internal sales organization or enter into collaboration arrangements with third parties 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 physicians to prescribe any of our product candidates; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and • unforeseen costs and expenses associated with creating an internal sales and marketing organization.
If we fail to remediate any material weaknesses or if we otherwise fail to establish and maintain effective control over financial reporting, our ability to accurately and timely report our financial results could be adversely affected.
If we fail to remediate any material weaknesses or if we otherwise fail to establish and maintain effective control over financial reporting, our ability to accurately and timely report our financial results could be adversely affected. 65 Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with adequate disclosure controls and procedures, are designed to prevent fraud.
In particular, a product may not be promoted for uses that are not approved by the FDA as reflected in the product’s approved labeling. If we receive marketing approval for our product candidates, physicians may nevertheless legally prescribe our products to their patients in a manner that is inconsistent with the approved label.
If we receive marketing approval for our product candidates, physicians may nevertheless legally prescribe our products to their patients in a manner that is inconsistent with the approved label. If we are found to have promoted such off-label uses, we may become subject to significant liability and government fines.
In the United States, the distribution of product samples to physicians must comply with the requirements of the U.S. Prescription Drug Marketing Act. Application holders must obtain FDA approval for product and manufacturing changes, depending on the nature of the change.
In the United States, the distribution of product samples to physicians must comply with the requirements of the U.S. Prescription Drug Marketing Act.
Current and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.
The RPD-PRV program is currently scheduled to sunset as of September 30, 2026, and the future of this program remains unknown at this time. Current and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.
Our business could be adversely affected by conditions in the U.S. and global economies, the United States and global financial markets and adverse geopolitical and macroeconomic developments, including rising inflation rates, the continuing adverse impacts of the COVID-19 pandemic, the Ukrainian/Russian and Israeli/Palestinian conflicts and related sanctions, bank failures, and economic uncertainties related to these conditions.
Our business could be adversely affected by conditions in the U.S. and global economies, the United States and global financial markets and adverse geopolitical and macroeconomic developments, including rising inflation rates, the continuing adverse impacts of the COVID-19 pandemic, the Ukrainian/Russian and Israeli/Palestinian conflicts and related sanctions, bank failures, and economic uncertainties related to these conditions. 66 For example, inflation rates, particularly in the United States, have increased recently to levels not seen in years, and increased inflation may result in increases in our operating costs (including our labor costs), reduced liquidity and limits on our ability to access credit or otherwise raise capital on acceptable terms, if at all.
Of the large number of biologics in development, only a small percentage result in the submission of a BLA to the FDA and even fewer are eventually approved for commercialization. As of the date of this report, we have not submitted a BLA to the FDA or comparable applications to other regulatory authorities for any of our product candidates.
Of the large number of biologics in development, only a small percentage result in the submission of a BLA to the FDA and even fewer are eventually approved for commercialization.
In the meantime, we will be obligated to rely on contract manufacturers for our preclinical research and clinical trials and commercial production, if and when any of our product candidates are approved for commercialization.
In the meantime, we will be obligated to rely on contract manufacturers for our preclinical research and clinical trials and commercial production, if and when any of our product candidates are approved for commercialization. 43 The facilities used by us or any contract manufacturer to manufacture our raw materials, manufacturing devices, active pharmaceutical ingredients and finished products must be approved by the FDA or comparable foreign regulatory authorities.
Similar requirements exist in many of these areas in other countries. 52 In addition, if any of our product candidates are approved for a particular indication, our product labeling, advertising and promotion would be subject to regulatory requirements and continuing regulatory review. The FDA strictly regulates the promotional claims that may be made about prescription products.
All of these activities are also potentially subject to U.S. federal and state consumer protection and unfair competition laws. Similar requirements exist in many of these areas in other countries. In addition, if any of our product candidates are approved for a particular indication, our product labeling, advertising and promotion would be subject to regulatory requirements and continuing regulatory review.
Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with adequate disclosure controls and procedures, are designed to prevent fraud. Any failure to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations.
Any failure to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations.
Medicaid Drug Rebate Program, the Federal Supply Schedule of the U.S. Department of Veterans Affairs, or other government drug programs, we will be subject to complex laws and regulations regarding reporting and payment obligations. All of these activities are also potentially subject to U.S. federal and state consumer protection and unfair competition laws.
False Claims Act, and similar state laws, which impact, among other things, our proposed sales, marketing, and scientific/educational grant programs. If we participate in the U.S. Medicaid Drug Rebate Program, the Federal Supply Schedule of the U.S. Department of Veterans Affairs, or other government drug programs, we will be subject to complex laws and regulations regarding reporting and payment obligations.
The facilities used by us or any contract manufacturer to manufacture our raw materials, manufacturing devices, active pharmaceutical ingredients and finished products must be approved by the FDA or comparable foreign regulatory authorities. Such approvals are subject to inspections that will be conducted after we submit a BLA to the FDA or their equivalents to other relevant regulatory authorities.
Such approvals are subject to inspections that will be conducted after we submit a BLA to the FDA or their equivalents to other relevant regulatory authorities.
Our business model includes the potential out-licensing or joint development of strains from our proprietary microbial library or our product candidates to other biopharmaceutical companies. Any such arrangement would typically begin with preliminary feasibility testing and evaluation by our potential partner or licensee.
Any such arrangement would typically begin with preliminary feasibility testing and evaluation by our potential partner or licensee.
We may also be subject, directly or indirectly through our customers and partners, to various fraud and abuse laws, including, without limitation, the U.S. Anti-Kickback Statute, U.S. False Claims Act, and similar state laws, which impact, among other things, our proposed sales, marketing, and scientific/educational grant programs. If we participate in the U.S.
Application holders must obtain FDA approval for product and manufacturing changes, depending on the nature of the change. 52 We may also be subject, directly or indirectly through our customers and partners, to various fraud and abuse laws, including, without limitation, the U.S. Anti-Kickback Statute, U.S.
In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In 2011, the U.S. Congress enacted the Budget Control Act of 2011, or the Budget Control Act, which included provisions intended to reduce the federal deficit.
It is unclear how such challenges, and the healthcare reform measures of the Biden administration will impact the ACA and our business. 55 In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In 2011, the U.S.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeIn addition, there can be no assurance that our internal information technology systems or those of our third-party contractors, or our consultants’ efforts to implement adequate security and control measures, will be sufficient to protect us against breakdowns, service disruption, data deterioration or loss in the event of a system malfunction, or prevent data from being stolen or corrupted in the event of a cyberattack, security breach, industrial espionage attacks or insider threat attacks which could result in financial, legal, business or reputational harm. 66 As of the date of this report, we are not aware of any risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, that have materially affected or are reasonably likely to materially affect us, including our business strategy, results of operations, or financial condition.
Biggest changeIn addition, there can be no assurance that our internal information technology systems or those of our third-party contractors, or our consultants’ efforts to implement adequate security and control measures, will be sufficient to protect us against breakdowns, service disruption, data deterioration or loss in the event of a system malfunction, or prevent data from being stolen or corrupted in the event of a cyberattack, security breach, industrial espionage attacks or insider threat attacks which could result in financial, legal, business or reputational harm.
Governance . Our senior management team conducts the regular assessment and management of material risks from cybersecurity threats, including review with our IT team and third-party service providers. All employees and consultants are directed to report to our senior management any irregular or suspicious activity that could indicate a cybersecurity threat or incident.
Our senior management team conducts the regular assessment and management of material risks from cybersecurity threats, including review with our IT team and third-party service providers. All employees and consultants are directed to report to our senior management any irregular or suspicious activity that could indicate a cybersecurity threat or incident.
The Audit Committee of our Board of Directors evaluates our cybersecurity assessment and management policies, including quarterly interviews with our senior officers and independent registered accounting firm.
The Audit Committee of our Board of Directors evaluates our cybersecurity assessment and management policies, including quarterly interviews with our senior officers and independent registered accounting firm. 67
Added
As of the date of this report, we are not aware of any risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, that have materially affected or are reasonably likely to materially affect us, including our business strategy, results of operations, or financial condition. Governance .

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeWe also lease approximately 1,868 square feet of office and laboratory space, which is located at 500 Cartier Boulevard, Laval, Quebec, Canada. We pay $6,882 per month under the lease. The lease expires in April 2026, subject to our option to extend the lease for an additional one-year term.
Biggest changeWe pay $7,235 per month under the lease plus our pro rata share of certain operating expenses of the property, and are currently renegotiating the lease terms. We also lease approximately 1,868 square feet of office and laboratory space, which is located at 500 Cartier Boulevard, Laval, Quebec, Canada. We pay $6,882 per month under the lease.
We believe that our facilities are adequate to meet our current needs and that additional space can be obtained on commercially reasonable terms as needed.
The lease expires in April 2026, subject to our option to extend the lease for an additional one-year term. We believe that our facilities are adequate to meet our current needs and that additional space can be obtained on commercially reasonable terms as needed.
We currently pay $14,385 per month under the lease, which will increase to $14,745 in 2025, plus our pro rata share of certain operating expenses of the property. We also lease approximately 1,093 square feet of additional laboratory space, which is located at 93 Shennecossett Road, Groton, Connecticut 06340.
We currently pay $14,745 per month under the lease, and are currently renegotiating the lease terms. We also lease approximately 1,093 square feet of additional laboratory space, which is located at 93 Shennecossett Road, Groton, Connecticut 06340. The lease expires in April 2026, with the option to extend the lease for an additional two one-year terms.
Removed
The lease expires in April 2025, subject to our option to extend the lease for an additional one-year term. We pay $7,235 per month under the lease plus our pro rata share of certain operating expenses of the property.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 4. Mine Safety Disclosures Not applicable. PART II
Biggest changeItem 4. Mine Safety Disclosures Not applicable. PART II. OTHER INFORMATION

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeItem 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Repurchases of Equity Securities Market Information Our common stock has trades on the NYSE American Stock Exchange under the symbol “AZTR.” 67 Holders of Record As of February 24, 2025, there were 34 holders of record of our common stock.
Biggest changeItem 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Repurchases of Equity Securities Market Information Our common stock is listed on the NYSE American Stock Exchange under the symbol “AZTR.” Holders of Record As of February 26, 2026, there were 35 holders of record of our common stock (including Cede & Co.).
Removed
Dividend Policy We have never declared or paid cash dividends on our common stock. We presently intend to retain earnings to finance the operation and expansion of our business.
Added
The actual number of stockholders is greater than this number of holders of record and includes stockholders who are beneficial owners but whose shares are held in “street name” by brokerage firms, banks and other financial institutions or nominees. Dividend Policy We have never declared or paid cash dividends on our common stock.
Removed
Equity Compensation Plan Information We have adopted the Azitra, Inc. 2016 Stock Incentive Plan, or 2016 Plan, providing for the grant of non-qualified stock options and incentive stock options to purchase shares of our common stock and for the grant of restricted and unrestricted share grants and restricted stock units.
Added
We presently intend to retain earnings to finance the operation and expansion of our business. 68 Securities Authorized for Issuance under Equity Compensation Plans Reference is made to the information contained in Item 12 of this Annual Report.
Removed
We currently have reserved 7,457 shares of our common stock under the 2016 Plan. The purpose of the 2016 Plan is to provide eligible participants with an opportunity to acquire an ownership interest in our company. All officers, directors, employees and consultants to our company are eligible to participate under the 2016 Plan.
Added
Unregistered Sales of Equity Securities There have been no other unregistered sales of equity securities during the year ended December 31, 2025, which have not been previously disclosed on a Current Report on Form 8-K.
Removed
The 2016 Plan provides that options may not be granted at an exercise price less than the fair market value of our shares of common stock on the date of grant.
Added
Issuer Purchases of Equity Securities None, In certain instances we provide our employees with the option to withhold shares to satisfy tax withholding amounts due from the employees upon the vesting of restricted stock units and stock options in connection with our 2016 Stock Incentive Plan and 2023 Stock Incentive Plan.
Removed
In March 2023, our Board and stockholders approved and adopted the Azitra, Inc. 2023 Stock Incentive Plan, or 2023 Plan, providing for the grant of non-qualified stock options and incentive stock options to purchase shares of our common stock and for the grant of restricted and unrestricted share grants and restricted stock units.
Added
There were no shares withheld during the quarter ended December 31, 2025 at the direction of the employees as permitted under either the 2016 Stock Incentive Plan or the 2023 Stock Incentive Plan, in order to pay the minimum amount of tax liability owed by the employee from the vesting of those units and options. Item 6. Reserved 69
Removed
We currently have reserved 1,209,735 shares of our common stock under the 2023 Plan.
Removed
On October 3, 2024, the Company’s Board of Directors approved amendments to the 2023 Plan that, subject to stockholder approval, would (i) increase the number of shares of Common Stock that may be issued under the 2023 Plan by 1,144,401 shares and (ii) adopt an evergreen provision to the 2023 Plan providing for an automatic 5% annual increase in the shares of Common Stock available for issuance under the 2023 Plan over the next 10 years commencing on January 1, 2026.
Removed
Both amendments were approved by the Company’s stockholders at the Company’s annual stockholder meeting held on November 20, 2024. The purpose of the 2023 Plan is to provide eligible participants with an opportunity to acquire an ownership interest in our company. All officers, directors, employees and consultants to our company are eligible to participate under the 2023 Plan.
Removed
The 2023 Plan provides that options may not be granted at an exercise price less than the fair market value of our shares of common stock on the date of grant. The following table sets forth certain information as of December 31, 2024 about our 2016 Plan and 2023 Plan under which our equity securities are authorized for issuance.
Removed
Plan Category (a) Number of Securities to be Issued Upon Exercise of Outstanding Options (b) Weighted- Average Exercise Price of Outstanding Options (c) Number of Securities Remaining Available for Future Issuance Under Equity Compensation Plans (Excluding Securities Reflected In Column (a)) Equity compensation plans approved by security holders 41,608 $41.60 1,209,735 Equity compensation plans not approved by security holders — — — Total 41,608 $41.60 1,209,735 68 Unregistered Sales of Equity Securities Unregistered Sale of Equity Securities None.

Item 7. Management's Discussion & Analysis

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

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Biggest changeYear Ended December 31, 2024 Compared to Year Ended December 31, 2023 The following table summarizes our results of operations with respect to the items set forth below for the years ended December 31, 2024 and 2023 together with the percentage change for those items. 73 Year Ended December 31, 2024 2023 $ Change % Change Service revenue - related party $ 7,500 $ 686,000 $ (678,500) (99) % Total revenue 7,500 686,000 (678,500) (99) % Operating expenses: General and administrative 6,269,262 4,493,332 1,775,930 40 % Research and development 4,723,378 3,643,214 1,080,164 30 % Total operating expenses 10,992,640 8,136,546 2,856,094 35 % Loss from operations (10,985,140) (7,450,546) (3,534,594) 47 % Non operating income (expense) Interest income 122,553 1,577 120,976 7671 % Interest expense (12,160) (167,726) 155,566 (93) % Change in fair value of convertible note — (3,630,100) 3,630,100 (100) % Change in fair value of warrants 4,034,072 34,930 3,999,142 (100) % Loss on issuance of common stock (2,132,800) — (2,132,800) (100) % Other income (expense) 15,014 (54,608) 69,622 (127) % Total other income (expense) 2,026,679 (3,815,927) 5,842,606 (153) % Loss before income taxes (8,958,461) (11,266,473) 2,308,012 (20) % Income tax expense (9,031) (17,308) 8,277 (48) % Net loss (8,967,492) (11,283,781) 2,316,289 (21) % Dividends on preferred stock — (1,355,347) 1,355,347 (100) % Net loss attributable to common shareholders $ (8,967,492) $ (12,639,128) $ 3,671,636 (29) % Service Revenue - Related Party We generated $7,500 of service revenue under the Bayer JDA during the year ended December 31, 2024 compared to service revenue of $686,000 under the JDA for the year ended December 31, 2023.
Biggest changeYear Ended December 31, 2025 2024 $ Change % Change Service revenue - related party Total revenue $ — $ 7,500 $ (7,500) (100) % — 7,500 (7,500) (100) % Operating expenses: General and administrative 6,130,657 6,269,262 (138,605) (2) % Research and development 4,836,008 4,723,378 112,630 2 % Total operating expenses 10,966,665 10,992,640 (25,975) — % Loss from operations (10,966,665) (10,985,140) 18,475 — % Other income (expense): Interest income 70,209 122,553 (52,344) (43) % Interest expense (7,587) (12,160) 4,573 (38) % Change in fair value of warrants 381 4,034,072 (4,033,691) (100) % Loss on issuance of common stock — (2,132,800) 2,132,800 (100) % Other (expense) income (43,389) 15,014 (58,403) (389) % Total other income 19,614 2,026,679 (2,007,065) (99) % Loss before income taxes (10,947,051) (8,958,461) (1,988,590) 22 % Income tax expense (8,319) (9,031) 712 — % Net loss attributable to common shareholders $ (10,955,370) $ (8,967,492) $ (1,987,878) 22 % Service Revenue - Related Party We generated $0 of service revenue under the Bayer JDA during the year ended December 31, 2025 compared to service revenue of $7,500 under the Bayer JDA for the year ended December 31, 2024.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations Cautionary Statement The following discussion and analysis should be read in conjunction with our statements and the related notes thereto contained elsewhere in this report.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations Cautionary Statement The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our financial statements and the related notes thereto contained elsewhere in this report.
In this report we make, and from time to time we otherwise make written and oral statements regarding our business and prospects, such as projections of future performance, statements of management’s plans and objectives, forecasts of market trends, and other matters that are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.
In this report we make statements, and from time to time we otherwise make written and oral statements regarding our business and prospects, such as projections of future performance, statements of management’s plans and objectives, forecasts of market trends, and other matters that are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934.
After submitting post-IND manufacturing reports, we have commenced operating activities for our Phase 1b clinical trial in December 2023, and we have dosed our first patient in August 2024.
After submitting post-IND manufacturing reports, we have commenced operating activities for our Phase 1b clinical trial in December 2023, and we dosed our first patient in August 2024.
In December 2022, we submitted an investigational new drug application, or IND, for a Phase 1b clinical trial of ATR-12 in adult Netherton syndrome patients, and on January 27, 2023 we received notification from the FDA that the “study may proceed” with respect to the proposed Phase 1b clinical trial.
In December 2022, we submitted an investigational new drug application, or IND, for a Phase 1b clinical trial of ATR-12 in Netherton syndrome patients, and on January 27, 2023 we received notification from the FDA that the “study may proceed” with respect to the proposed Phase 1b clinical trial.
If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, limit, reduce or terminate our research, product development or future 75 commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, limit, reduce or terminate our research, product development or future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
Overview We focused on developing innovative therapies for precision dermatology using engineered proteins and topical live biotherapeutic products. We have built a proprietary platform that includes a microbial library comprised of approximately 1,500 unique bacterial strains that can be screened for unique therapeutic characteristics.
Overview We are focused on developing innovative therapies for precision dermatology using engineered proteins and topical live biotherapeutic products. We have built a proprietary platform that includes a microbial library comprised of approximately 1,500 unique bacterial strains that can be screened for unique therapeutic characteristics.
We hold an exclusive, worldwide license from Fred Hutch regarding the use of its patented SyngenicDNA Minicircle Plasmid, or SyMPL, technologies for all fields of genetic engineering, including to discover, develop and 71 commercialize engineered microbial therapies and microbial-derived peptides and proteins for skin diseases.
We hold an exclusive, worldwide license from Fred Hutch regarding the use of its patented SyngenicDNA Minicircle Plasmid, or SyMPL, technologies for all fields of genetic engineering, including to discover, develop and commercialize engineered microbial therapies and microbial-derived peptides and proteins for skin diseases.
In August 2024, we obtained IND clearance from the FDA to commence a Phase 1/2 clinical trial in certain cancer patients undergoing EGFRi targeted therapy. In September 2024, we obtained Fast Track designation by the FDA in this indication.
In August 2024, we obtained IND clearance from the FDA to commence a Phase 1/2 clinical trial in certain cancer patients undergoing EGFRi 72 targeted therapy. In September 2024, we obtained Fast Track designation by the FDA in this indication.
In 2022, we obtained pre-IND correspondence with the FDA for purposes of discussing our proposed regulatory pathway for ATR-12 and obtaining guidance from the FDA on the preclinical plan leading to the filing and acceptance of an IND for ATR-12. In December 2022, we filed an IND for a first-in-human trial of ATR-12 in Netherton syndrome patients.
In 2022, we obtained pre-IND correspondence with the FDA for purposes of discussing our proposed regulatory pathway for the ATR-12 program and obtaining guidance from the FDA on the preclinical plan leading to the filing and acceptance of an IND for ATR-12. In December 2022, we filed an IND for an ATR-12 first-in-human trial in Netherton syndrome patients.
On January 27, 2023, we received notification from the FDA that the “study may proceed” with respect to the proposed Phase 1b clinical trial, and in August 2024 we initiated dosing the first patient in its Phase 1b clinical trial evaluating ATR-12.
On January 27, 2023, we received notification from the FDA that the “study may proceed” with respect to the proposed Phase 1b clinical trial, and in August 2024 we initiated dosing the first patient in the ATR-12 Phase 1b clinical trial.
The preparation of these consolidated financial statements requires us to make judgments and estimates that affect the reported amounts of assets, liabilities, and expenses and the disclosure of contingent assets and liabilities in our consolidated financial statements.
The preparation of these condensed financial statements requires us to make judgments and estimates that affect the reported amounts of assets, liabilities, and expenses and the disclosure of contingent assets and liabilities in our condensed financial statements.
Our initial focus is on the development of our current product candidates, including: • ATR-12 , a genetically modified strain of S. epidermidis for treating the orphan disease, Netherton syndrome, a chronic and sometimes fatal disease of the skin estimated to affect approximately one to nine in every 100,000, but its prevalence may be underestimated due to misdiagnosis caused by similarities to other skin diseases.
Our initial focus is on the development of our current programs, including: • ATR-12 , which includes a genetically modified strain of S. epidermidis for treating the orphan disease, Netherton syndrome, a chronic and sometimes fatal disease of the skin estimated to affect approximately one in every 100,000, but its prevalence may be underestimated due to misdiagnosis caused by similarities to other skin diseases.
We urge you to carefully review and consider the various disclosures made by us in this report and in our other filings with the Securities and Exchange Commission, or SEC, including the "Risk Factors" section in this report.
We urge you to carefully review and consider the various disclosures made by us in this report and in our other filings with the Securities and Exchange Commission, or SEC, including the “Risk Factors” section in this report.
We believe our genetic engineering techniques and technologies have applicability outside of the field of medicine, including cosmetics and in the generation of clean fuels and bioremediation. 72 • Leverage our academic partnerships. We currently have partnerships with investigators at the Fred Hutchinson Cancer Center, Yale University, Jackson Laboratory for Genomic Medicine, and Carnegie Mellon University.
We believe our genetic engineering techniques and technologies have applicability outside of the field of medicine, including cosmetics and in the generation of clean fuels and bioremediation. • Leverage our academic partnerships. We currently have partnerships with investigators at the Fred Hutchinson Cancer Center, Yale University, Duke University, and Carnegie Mellon University.
The effects of material revisions in estimates, if any, will be reflected in the consolidated financial statements prospectively from the date of change in estimates.
The effects of material revisions in estimates, if any, will be reflected in the condensed financial statements prospectively from the date of change in estimates. 78
We expect to dose the first patient in the Phase 1/2 clinical trial in the first half of 2025. 70 • ATR-01 , a genetically modified strain of S. epidermidis that expresses an engineered recombinant human filaggrin protein for treating ichthyosis vulgaris, a chronic, xerotic (abnormally dry), scaly skin disease with an estimated incidence and prevalence of 1 in 250, which suggests a total patient population of 1.3 million in the United States.
We dosed the first patient in the Phase 1/2 clinical trial in the third quarter of 2025. • ATR-01 , which includes a genetically modified strain of S. epidermidis that expresses an engineered recombinant human filaggrin protein for treating ichthyosis vulgaris, a chronic, xerotic (abnormally dry), scaly skin disease with an estimated incidence and prevalence of 1 in 250, which suggests a total patient population of 1.3 million in the United States.
We expect to report initial safety results in the first half of 2025. • ATR-04 , a genetically modified strain of S. epidermidis for treating the papulopustular rash experienced by cancer patients undergoing epidermal growth factor receptor inhibitor, or EGFRi, targeted therapy.
We reported initial clinical safety results in the first half of 2025. • ATR-04 , which includes a genetically modified strain of S. epidermidis for treating the papulopustular rash experienced by cancer patients undergoing epidermal growth factor receptor inhibitor, or EGFRi, targeted therapy.
However, we believe that SyMPL will open up the ability to make genetic transformations of an expanded universe of microbial species, and we expect that some or all of our future product candidates will incorporate the SyMPL technology. Our collaboration with Fred Hutch is led by Dr.
However, we believe that SyMPL will open up the ability to make genetic transformations of an expanded universe of microbial species, and we expect that some or all of our future product candidates will incorporate the SyMPL technology.
We expect to report initial safety results of the first patients dosed in our Phase 1b clinical trial for our ATR-12 in Netherton syndrome patients in early 2025 with full results anticipated in the second half of 2025. • Broaden our platform by selectively exploring strategic partnerships that maximize the potential of our precision dermatology programs.
We reported initial safety results of the first patients dosed in our Phase 1b clinical trial for our ATR-12 program in Netherton syndrome patients in the first half of 2025. • Broaden our platform by selectively exploring strategic partnerships that maximize the potential of our precision dermatology programs.
To date, our operations have consisted of the development of our proprietary microbial library, the identification, characterization and testing of certain bacterial species from our microbial library that we believe are capable of being engineered to provide significant therapeutic effect and the development of our initial product candidates.
To date, our operations have consisted of the development of our proprietary microbial library, the identification, characterization and testing of certain bacterial species from our microbial library that we believe are capable of being engineered to provide significant therapeutic effect, the development of our initial product candidates and the commencement of phase 1/2 clinical trials related to our ATR-12, and ATR-04 product candidates.
In August 2024, we received IND clearance from the FDA for a first-in-human Phase 1b/2a clinical trial in patients with EGFRi-associated rash, and in September 2024, the FDA granted Fast Track designation for ATR-04. We commenced a Phase 1b trial of our ATR-04 in certain cancer patients undergoing EGFRi therapy in the fourth quarter of 2024.
In August 2024, we received IND clearance from the FDA for a first-in-human Phase 1b/2a clinical trial in patients with EGFRi-associated rash, and in September 2024, the FDA granted Fast Track designation for the ATR-04 program.
Our strategy is as follows: • Build a sustainable precision dermatology company. Our goal is to build a leading precision dermatology company with a sustainable pipeline of product candidates. To that end, we are focused on rapidly advancing our current pipeline of live biotherapeutic candidates while actively developing additional product candidates.
Our goal is to build a leading precision dermatology company with a sustainable pipeline of product candidates. To that end, we are focused on rapidly advancing our current pipeline of live biotherapeutic candidates while actively developing additional product candidates. Each of our current product candidates are proprietary and subject to pending patent applications.
As of the date of this report, we have identified among our microbial library over 60 distinct bacterial species that we believe are capable of being engineered to create living organisms or engineered proteins with significant therapeutic effect. We are a pioneer in genetically engineered bacteria for therapeutic use in dermatology.
The particular species demonstrates a number of well-described properties in the skin. As of the date of this report, we have identified among our microbial library over 60 distinct bacterial species that we believe are capable of being engineered to create living organisms or engineered proteins with significant therapeutic effect.
Our goal is to leverage our platforms and internal microbial library bacterial strains to create new therapeutics that are either engineered living organisms or engineered proteins or peptides to treat skin diseases.
We are a pioneer in genetically engineered bacteria for therapeutic use in dermatology. Our goal is to leverage our platforms and internal microbial library bacterial strains to create new therapeutics that are either engineered living organisms or engineered proteins or peptides to treat skin diseases.
Each of our current product candidates are proprietary and subject to pending patent applications. We expect that most, if not all, genetically engineered product candidates we develop will be eligible for patent protection. • Advance our lead product candidates, ATR-12 and ATR-04, through clinical trials.
We expect that most, if not all, genetically engineered product candidates we develop will be eligible for patent protection. 73 • Advance our lead programs, ATR-12 and ATR-04, through clinical trials.
To date, we have capitalized our operations primarily through a series of private placements of our convertible preferred stock and convertible promissory notes and our initial public offering, IPO, of common stock which closed on June 21, 2023 and subsequent offerings.
To date, we have capitalized our operations primarily through a series of private placements of our convertible preferred stock and convertible promissory notes and our initial public offering, IPO, of common stock which closed on June 21, 2023. In connection with our IPO, we issued 7,508 shares of our common stock at a public offering price of $999 per share.
Non-operating income (expense) Our non-operating income (expense) consists of refundable research and development credits, change in the valuation of warrants carried at fair market value, loss on the issuance of stock, loss on disposal of equipment, loss on foreign currency translation, change in fair value of the convertible note, interest income, and interest expense.
Other Income Our other income consists of interest income, loss on issuance of stock, loss on foreign currency translation, change in the valuation of warrants carried at fair value, loss on issuance of common stock, loss on disposal of property and equipment, and interest expense.
Except as otherwise indicated, all share and share price amounts in this report gives effect to a forward stock split effected on May 17, 2023 at a ratio of 7.1-for-1, and the reverse stock split effected on July 1, 2024 at a ratio of 1-for-30.
Except as otherwise indicated, all share and share price herein give effect to a forward stock split effected on May 17, 2023 at a ratio of 7.1 for one, a reverse stock split effected on July 1, 2024 at a ratio of one for 30 and a reverse stock split effected on August 21, 2025 at a ratio of one for 6.66.
We believe that we have established a unique position in advancing the development of biologics for precision dermatology. We intend to create a broad portfolio of product candidates for precision dermatology through our development of genetically engineered proteins selected from our proprietary microbial library of approximately 1,500 unique bacterial strains.
We intend to create a broad portfolio of product candidates for precision dermatology through our development of genetically engineered proteins selected from our proprietary microbial library of approximately 1,500 unique bacterial strains. Our strategy is as follows: • Build a sustainable precision dermatology company.
After giving effect to both offerings, we believe that our cash on-hand as of the date of this report will be not sufficient to cover our proposed plan of operations beyond six months from the date of this report.
We believe that our cash on-hand as of the date of this report will not be sufficient to cover our proposed plan of operations over the next twelve months and thereafter.
Cash Flows The following table shows a summary of our cash flows for the periods indicated: December 31, 2024 2023 Net cash used in operating activities $ (10,183,740) $ (7,362,375) Net cash used in investing activities $ (379,246) $ (318,259) Net cash provided by financing activities $ 13,321,716 $ 5,983,967 Net decrease in cash $ 2,758,730 $ (1,696,667) Operating Activities During the year ended December 31, 2024, operating activities used $10.2 million of cash primarily driven by our net loss of $9.0 million and by non-cash items of $1.2 million.
Cash Flows The following table shows a summary of our cash flows for the periods indicated: December 31, 2025 2024 Net cash used in operating activities $ (11,224,125) $ (10,183,740) Net cash used in investing activities $ (182,909) $ (379,246) Net cash provided by financing activities $ 8,920,398 $ 13,321,716 Net (decrease) increase in cash $ (2,486,636) $ 2,758,730 Operating Activities During the year ended December 31, 2025, operating activities used $11.2 million of cash primarily driven by our net loss of $10.9 million.
Our initial focus is on the development of genetically engineered strains of Staphylococcus epidermidis, or S. epidermidis , which we consider to be an optimal therapeutic candidate species for engineering of dermatologic therapies. The particular species demonstrates a number of well-described properties in the skin.
The platform is augmented by an artificial intelligence and machine learning technology, which can enable the transformation of previously genetically intractable strains. Our initial focus is on the development of genetically engineered strains of Staphylococcus epidermidis, or S. epidermidis , which we consider to be an optimal therapeutic candidate species for engineering of dermatologic therapies.
During fiscal 2023, financing activities provided $6.0 million in cash primarily driven by the proceeds from our initial public offering. Critical Accounting 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.
Our management’s discussion and analysis of our financial condition and results of operations are based on our condensed financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles.
In connection with our IPO, we issued 1.5 million shares of our common stock at a public offering price of $5 per share. Concurrent with the close of our IPO, all of our outstanding shares of convertible preferred stock and convertible promissory notes converted into a total of 8,951,526 shares of our common stock.
Concurrent with the close of our IPO, all of our outstanding shares of convertible preferred stock and convertible promissory notes converted into a total of 44,802 shares of our common stock.
We intend to seek additional funds through various financing sources, including the sale of our equity and debt securities, licensing fees for our technology and joint ventures with industry partners. In addition, we will consider alternatives to our current business plan that may enable us to achieve revenue producing operations and meaningful commercial success with a smaller amount of capital.
We intend to seek additional funds through various financing sources, including the sale of our equity and debt securities, federal grants, licensing fees for our technology and joint ventures with industry partners.
During fiscal 2023, investing activities used $0.3 million of cash primarily driven by $0.3 million of deferred patent costs and patent and trademark costs. Financing Activities During the year ended December 31, 2024, financing activities provided $13.3 million in cash primarily driven by proceeds from our follow-on public offerings.
During the fiscal 2024, financing activities provided $13.3 million in cash primarily driven by proceeds from our February 2024 follow-on offering.
In July 2024, we completed a follow-on public offering in which we issued 69 6,665,000 shares of our common stock at a price of $1.50 per share and Class A Warrants exercisable for an aggregate 13,330,000 shares of common stock.
On July 25, 2024, we completed a follow-on offering of an aggregate of 1,000,750 shares of our common stock, and Class A warrants to purchase up to 2,001,502 shares of common stock, at a combined public offering price of $9.99 per share and accompanying warrants.
During fiscal 2023, operating activities used $7.4 million of cash primarily driven by our net loss of $11.3 million offset by non-cash items of $3.9 million. Investing Activities During the year ended December 31, 2024, investing activities used $0.4 million of cash primarily driven by $0.4 million of deferred patent costs and patent and trademark costs.
During fiscal 2024, operating activities used $10.2 million of cash primarily driven by our net loss of $9.0 million and by non-cash items of $1.2 million.
There was no government and nonprofit grant revenue received by us during fiscal year 2024 or 2023, and do not expect any future grant revenue at this time. We expect our research and development expenses to significantly increase in the future due primarily to our planned clinical trial activity and continued development of product candidates.
We expect our research and development expenses to significantly increase in the future due primarily to our planned clinical trial activity and continued development of product candidates.
Christopher Johnston, an expert in microbial engineering, and the innovator behind the SyMPL technology. Our Strategy Beyond our three lead product candidates and collaboration with Bayer, our goal is to develop a broad portfolio of product candidates focused on expanding the application of our platforms for precision dermatology.
Our Strategy Beyond our three lead product candidates, our goal is to develop a broad portfolio of product candidates focused on expanding the application of our platforms for precision dermatology. We believe that we have established a unique position in advancing the development of biologics for precision dermatology.
However, there can be no guarantees that such funds will be available on commercially reasonable terms, if at all. If such financing is not available on satisfactory terms, we may be required to scale back our proposed plan of operations and we may be unable to continue operations.
If such financing is not available on satisfactory terms, we may be unable to further pursue our business plan and we may be unable to continue operations.
Bayer holds the exclusive option to license the patent rights to these strains. We also have established partnerships with teams from Carnegie Mellon University and the Fred Hutchinson Cancer Center, or Fred Hutch, two of the premier academic centers in the United States.
We are planning to perform lead optimization and IND-enabling studies in 2025 to support a potential IND filing in 2026. We also have established partnerships with teams from Carnegie Mellon University and the Fred Hutch, two of the premier academic centers in the United States.
In January 2025, we completed a public offering of 4,857,780 shares of our common stock, at an offering price of $0.30 per share, in which we received net proceeds of approximately $1.3 million, after deducting underwriter discounts and offering expenses, and in February 2025 we completed a registered direct offering of 2,495,5818 shares of our common stock, at an offering price of $0.2785 per share, in which we received net proceeds of approximately $695 thousand, after deducting placement agent commissions and offering expenses.
On January 16, 2025, we completed a follow-on offering in which we issued and sold 729,381 shares of our common stock at a price of $2.00 per share. The net proceeds received by us from the follow-on offering were $1.2 million, after deducting placement agent's fees and other offering expenses.
We expect to dose the first patient in the Phase 1/2 clinical trial with ATR-04 in the first half of 2025.
We commenced a Phase 1b trial for our ATR-04 program in certain cancer patients undergoing EGFRi therapy in the fourth quarter of 2024 and initiated dosing the first patient in the ATR-04 Phase 1/2 clinical trial in the third quarter of 2025.
Due to our accumulated deficit, recurring and negative cash flow from operations there is substantial doubt about our ability to continue as a going concern.
As of the date of this filing, management has determined there is substantial doubt about our ability to continue as a going concern based on our lack of revenue from commercial operations, significant losses, and the need to raise additional capital to support ongoing operations.
This was offset by a one-time $2.1 million loss attributable to the issuance of stock, and a a net increase of $0.3 million attributable to other income (expense). Financial Condition As of December 31, 2024, we had total assets of approximately $7.4 million and working capital of approximately $3.9 million.
We expect our future other income (expense) to be consistent with prior periods. 76 Liquidity and Capital Resources As of December 31, 2025, we had total assets of approximately $5.0 million and working capital of approximately $2.0 million. As of December 31, 2025, our liquidity included approximately $2.1 million of cash and cash equivalents.
Removed
The net proceeds received by us from the follow-on public offering were $9.1 million, after deducting underwriting discounts, commissions and other offering expenses. The Class A Warrants had an initial exercise price of $1.50 that was adjusted to $0.7043 in accordance with a reset price provision determined 30 days following the issuance date.
Added
In February 2024, we completed a follow-on public offering in which we issued and sold 83,404 shares of our common stock at a price to the public of $59.94 per share.
Removed
As of February 24, 2025, we had 14,979,354 shares of our common stock issued and outstanding.
Added
The shares were offered by us pursuant to a shelf registration statement on Form S-3 filed with the SEC on July 1, 2024, and a final prospectus supplement dated January 15, 2025.
Removed
The platform is augmented by an artificial intelligence and machine learning technology that analyzes, predicts and helps screen our library of strains for drug like molecules. The platform also utilizes a licensed genetic engineering technology, which can enable the transformation of previously genetically intractable strains.
Added
On February 5, 2025, we completed a follow-on offering in which we issued 374,696 shares of our common stock at a public offering price of $1.85 per share and warrants to purchase up to 337,232 shares of common stock.
Removed
We are planning to perform lead optimization and IND-enabling studies in 2025 to support an IND filing . • Two separate strains of bacterial microbes are being investigated and developed by us and Bayer Consumer Care AG, the consumer products division of Bayer AG, or Bayer, the international life science company.
Added
The net proceeds received by the Company from the follow-on offering were approximately $561,000 after deducting placement agent's fees and other offering expenses. The shares were offered by us pursuant to a shelf registration statement on Form S-3 filed with the SEC on July 1, 2024, and a final prospectus supplement dated February 4, 2025.
Removed
We entered into a Joint Development Agreement, or JDA, with Bayer in December 2019. Under the terms of the JDA, we are responsible for testing our library of bacterial strains and their natural products for key preclinical properties. After screening through hundreds of strains, we and Bayer have selected two particular strains to move forward into further development.
Added
The warrants became exercisable on the six-month and one day anniversary of their issuance, and their exercise price is $3.60.
Removed
Our ability to genetically engineer intractable microbial species is uniquely leveraged by our exclusive license to the SyMPL technology. Results of Operations We are an early-stage clinical biopharmaceutical company, formed in January 2014, and have limited operating history. We have not commenced revenue-producing operations apart from limited service revenue derived through our JDA with Bayer.
Added
On April 24, 2025, the Company entered into a Purchase Agreement (the "ELOC Purchase Agreement") with Alumni Capital LP (the "Purchaser" or "Alumni Capital"), whereby the Company has the right, but not the obligation, to sell to the Purchaser, and the Purchaser is obligated to purchase, up to an aggregate of $20 million (the "Investment Amount") of shares of the Company’s common stock in a series of purchases (the “ELOC Shares”).
Removed
Under the terms of the JDA, we are responsible for testing our library of microbial strains and their natural products for key preclinical properties and Bayer reimburses us for our development costs.
Added
The term of the ELOC Purchase Agreement is through December 31, 2026, or the date on which the Purchaser shall have purchased the shares pursuant to the ELOC Purchase Agreement for an aggregate purchase price of the Investment Amount.
Removed
The decrease of $(678,500) in service revenue is attributable to a decrease in the amount of reimbursable development costs in 2024, and the Company does not expect any significant future revenue under the Bayer JDA.
Added
During the term, the Company may at its election cause the Purchaser to make a series of purchases 70 of shares, each up to $750,000, or up to $4 million dollars upon consent of the Purchaser.
Removed
General and Administrative General and administrative costs during the year ended December 31, 2024 increased by $1.8 million, or 40%, to $6.3 million from the prior year.
Added
The closing of each purchase pursuant to the ELOC Purchase Agreement will be no later than five business days after the Company provides a notice to for the purchase.
Removed
The increase was primarily related to the costs incurred following, and a result of, our emergence as a public company in June 2023, including $1.2 million of salaries and benefits primarily attributable to hiring our CFO and COO, an increase of $111,000 primarily related to the achievement of a milestone for our CEO's performance based options, an increase of $172,000 in public relations, an increase of $162,000 of insurance costs and a net increase of $111,000 in other overhead expenses. 74 Research and Development Research and development expenses include salaries and benefits of all research personnel, payments to contract research organizations, payments to research consultants, and the purchase of lab supplies.
Added
The purchase price of the ELOC Shares that the Company elects to sell to the Purchaser pursuant to the ELOC Purchase Agreement will be equal to the lowest daily volume weighted average price of the common stock during the period commencing on the date that the Company delivers a notice requiring the purchase of shares by the Purchaser and ending on the earlier to occur of (i) five (5) business days immediately following such date and (ii) the date on which the Purchaser notifies the Company that it is prepared to proceed with the relevant closing, multiplied by 90%.
Removed
These expenses are offset by income earned from government grant payments. During the year ended December 31, 2024, research and development expenses increased by $1.1 million, or 30%, to $4.7 million from the prior year period.
Added
Upon each purchase, the Purchaser will receive warrants to purchase such number of shares of the Company’s common stock equal to 10% of the number of ELOC Shares purchased in the related purchase (the “ELOC Warrants”). The Exercise Price shall equal 130% of the price per ELOC Share paid upon closing.
Removed
The increase was primarily related to an increase of $450,000 in payroll related costs, $500,000 in research and development related costs attributable to our efforts in moving our EGFR program forward, an increase of $37,000 in moving our Netherton program forward, and a net increase of $113,000 of other costs.
Added
The exercise of the ELOC Warrant will be subject to stockholder approval and expire five years after issuance. The ELOC Warrants may be exercised via cashless exercise if there is no effective registration statement, or current prospectus available for, the resale of the ELOC Warrant Shares.
Removed
During the year ended December 31, 2024, non-operating income (expense) increased by $5.8 million, or (153)%, compared to the comparable period in fiscal 2023. The increase was primarily attributable to a $3.6 million decrease in fair value of the convertible note and an increase of $4.0 million attributable to the decrease in valuation of the warrants.
Added
The ELOC Shares and ELOC Warrants have been registered under the Registration Statements on Form S-1 (File Nos. 333-286809 and 333-292049).
Removed
As of December 31, 2024, our liquidity included approximately $4.6 million of cash and cash equivalents.
Added
The Company could not issue to the Purchaser under the Purchase Agreement shares in an amount greater than 19.99% of the total number of shares of common stock issued and outstanding immediately prior to the execution of the ELOC Purchase Agreement (the “Exchange Cap”), unless the Company obtained stockholder approval to issue shares of common stock in excess of the Exchange Cap.
Removed
In January 2025, we completed a public offering of shares of our common stock for the net proceeds of approximately $1.3 million, and in February 2025 we completed a registered direct offering of shares of our common stock for the net proceeds of approximately $695 thousand.
Added
On June 23, 2025, at the Company's annual meeting of stockholders, the stockholders approved the sale and issuance of more than 19.99% of our outstanding shares of our common stock, including shares of common stock underlying warrants, pursuant to the Purchase Agreement entered into with the Purchaser.
Removed
Our financial statements include disclosure with respect to a substantial doubt about our ability to continue as a going concern and the report of our independent auditor includes an explanatory paragraph with respect to that substantial doubt.
Added
On August 26, 2025, the Company entered into a Modification Agreement (the “Modification Agreement”) with Alumni Capital to amend certain terms of the ELOC Purchase Agreement.
Added
Pursuant to the Modification Agreement, the Company may at its election, cause Alumni Capital to make a series of purchases of ELOC Shares either at (i) the lowest daily volume weighted average price of the common stock during the period commencing on the date that the Company delivers written notice (the “Purchase Notice”) and ending on the earlier of (a) five (5) business days immediately following the date of a Purchase Notice, and (b) the date on which Alumni Capital notifies the Company that it is prepared to proceed with the closing of the purchase, multiplied by 90% (“Purchase Notice Option 1”) or (ii) the lowest traded price of common stock during the period commencing on the date the Company delivers a Purchase Notice and ending on the earlier of (x) the same business day a Purchase Notice is delivered, and (y) the date on which Alumni Capital notifies the Company that it is prepared to proceed with the closing of the purchase, multiplied by 97% (“Purchase Notice Option 2”).

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