What changed in this filing

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Item 1. Business

2026-03-26 compared with 2025-03-27 · 102 added, 130 removed, 516 unchanged (31% of the section changed)

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In September 2024, we reported results from a first-in-human Phase 1 clinical trial completed in Australia to assess the safety, tolerability, pharmacokinetics, and food effect of GT-02287 in healthy participants.

The study enrolled 72 healthy volunteers and included a single ascending dose part during which the study participants (n=40) received one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which the study participants (n=32) received one daily dose of GT-02287 for 14 days at different dose levels.

The study enrolled 72 healthy volunteers and included a single ascending dose part during which study participants (n=40) received one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which study participants (n=32) received one daily dose of GT-02287 for 14 days at different dose levels.

Review of the unblinded data after database lock confirmed that single and multiple doses of GT-02287 were safe and generally well tolerated up to and including the highest planned dose levels across all age groups (approximately 15% of which were over the age of 50 years).

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GT-02287 was measurable in cerebrospinal fluid (CSF) at levels in line with rodent levels at effective doses from our preclinical models, demonstrating CNS exposure.

Notably, GCase activity in dried blood spots increased approximately 53% in subjects who received 13.5 mg/kg GT-02287 (the highest dose cohort and the only dose cohort analyzed for GCase activity) but not in those who received placebo, demonstrating target engagement and modulation of GCase enzyme.

Notably, mean GCase activity in dried blood spots increased 53% in subjects who received 13.5 mg/kg GT-02287 (the highest dose cohort and the only dose cohort analyzed for GCase activity) but not in those who received placebo, demonstrating target engagement and modulation of GCase enzyme.

GCase activity continued to increase 12 hours post-dose at 14 days, the furthest time point analyzed in the study.

We believe these results support the continued development of GT-02287 and its potential as a biology-modifying treatment for Parkinson’s disease.

Importantly, the favorable safety and tolerability profile at oral dose levels that resulted in therapeutic plasma levels, CNS exposure, and target engagement further strengthens GT-02287’s potential to be a lead treatment for Parkinson’s disease in patients with or without a GBA1 mutation.

In December 2024, we received approval in Australia to initiate a Phase 1b trial for GT-02287 in people with Parkinson’s disease with or without the GBA1 mutation.

We are working with local Parkinson’s disease (PD) advocacy groups in Australia to support enrollment and expect enrollment to complete in the summer of 2025 with interim data from the study expected by mid-2025.

The Phase 1b open-label trial will assess the safety and tolerability of 13.5 mg/kg/day of GT-02287 for three months in patients with GBA1-PD or idiopathic Parkinson’s disease.

Secondary endpoints include pharmacokinetics, GCase modulation, levels of GCase substrates, and other biomarkers in plasma and cerebrospinal fluid.

The primary goal of the Phase 1b trial is to assess the safety and tolerability of GT-02287.

Upon successful completion we expect to begin planning a Phase 2 study during the second half of 2025.

In preparation for the treatment of Parkinson’s disease patients, we initiated a chronic (6 months in rodents and 9 months in non-rodents) preclinical toxicity study in July 2024, enabling the conduct of clinical studies in patients with a GT-02287 treatment duration beyond three months.

The 6- and 9-month studies will be completed in the second quarter of 2025 and the third quarter of 2025, respectively.

In December 2024, we received approval in Australia to initiate a Phase 1b open-label safety and tolerability study for GT-02287 in 15-20 people with Parkinson’s disease with or without a GBA1 mutation.

The study consists of a 90-day Part 1 and an optional 9-month extension (Part 2).

Enrollment was completed in September of 2025, and Part 1 was completed in November 2025.

This study’s secondary and exploratory endpoints include pharmacokinetics, GCase modulation, levels of GCase sphingolipid substrates, and other biomarkers in plasma and cerebrospinal fluid.

Part 2 of the Phase 1b study is expected to be complete in the third quarter of 2026, and we are currently planning a Phase 2 study to commence during the second half of 2026.

Our Magellan™ Platform

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the ability to regulate proteins implicated in disease through several different mechanisms of action covering both functional and conformational effects, including stabilization, destabilization, targeted degradation, allosteric inhibition, and allosteric activation of the targeted protein;

improved specificity of small molecules because binding to an allosteric binding site is non-competitive with the natural substrate that binds to the active binding site;

specificity of small molecules because binding to an allosteric binding site is non-competitive with the natural substrate that binds to the active binding site;

and the ability to identify small molecules with more favorable drug-like properties.

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We refer to the small molecules we identify that bind to these allosteric sites as structurally targeted allosteric regulators, or STARs, to reflect their mechanism of action and how they are discovered.

The graphic below provides an overview of Magellan™.

Allosteric Binding Site Identification

Using the three-dimensional structure of proteins that have been experimentally derived or generated or predictive protein structures from AI-powered databases such as Alphafold, our Magellan™ platform applies various computational methods and proprietary algorithms to identify and map previously uncharacterized clusters of binding

hotspots on the protein surface where a small molecule can potentially bind.

The number, density, nature and quality of these hotspot clusters determine the druggability of the protein, which refers to whether drug-like small molecules can effectively bind to the particular site on the target protein with an appropriate potency.

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Identification of Structurally Targeted Allosteric Regulators (“STARs”) – Our Molecular Hypothesis

After an allosteric site has been identified, characterized and selected for targeting, we then use our proprietary structure-based virtual screening methodology to explore virtual chemical libraries of over 50 billion compounds to identify those that may bind to the hotspot and have a functional effect.

After an allosteric site has been identified, characterized and selected for targeting, we then use our proprietary, AI-driven structure-based virtual screening methodology to explore virtual chemical libraries totaling potentially trillions of compounds to identify those that may bind to the hotspot and have a functional effect.

Using this information, we develop structural templates to guide the development of a narrowed pool of unique and proprietary small molecules that bind to the newly discovered allosteric sites.

We believe our process for identifying STARs provides several advantages over traditional drug discovery approaches such as random high-throughput screening.

In high-throughput screening, very large libraries of randomly selected molecules are tested for their ability to perform a specific function such as binding to a target protein.

This approach typically results in a large number of positive hits that must then be laboriously analyzed to identify compounds with relevant properties and effect.

A high-throughput screening campaign may take up to two years or more to complete, and, on average, only 0.1% of all compounds tested in this manner bind to the targeted protein with the desired effect.

In contrast, our approach is significantly less expensive, significantly faster and significantly more effective.

We run our Magellan™ simulations for target and drug discovery in supercomputer centers where we pay only for time used as and when needed.

We can identify a novel allosteric site in one to two weeks, set up and complete virtual screening in three to four weeks, and validate compounds experimentally in two to three weeks.

Our average success rate for experimentally validated compounds is 14%, a greater than 100-fold higher success rate compared to traditional high throughput screening methods.

Further, every small molecule hit identified by our platform is experimentally tested based on a two-part molecular hypothesis to confirm that (1) the compound has a positive effect on the relevant biomarkers implicated in the disease and (2) binding to the allosteric binding site identified with the Magellan™ platform has the intended effect on protein function.

We believe our approach can be significantly less expensive, significantly faster and significantly more effective.

Allosteric Regulators Cover Several Mechanisms of Action

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However, in areas such as oncology, we have identified STARs that are designed to destabilize target proteins by binding to a non-native or mutant form of the protein and render it inactive.

There are several additional potential mechanisms of action including allosteric targeted protein degradation, as well as traditional allosteric inhibition or activation by inducing a

conformational change to inhibit or induce binding by the natural ligand of the active site of the protein.

The graphic below provides an overview of the different mechanisms of action available through allosteric binding sites.

There are several additional potential mechanisms of action including allosteric targeted protein degradation, as well as traditional allosteric inhibition or activation by inducing a conformational change to inhibit or induce binding by the natural ligand of the active site of the protein.

Enzyme Misfolding and Disease

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Current therapeutic approaches to address misfolded enzymes have inherent limitations.

Drugs that bind to the active site of the enzyme or other target proteins impair the protein’s function to some degree by competing with the active substrate, decreasing efficacy and potentially leading to selectivity issues.

Drugs that bind to the active site of the enzyme or other target proteins impair the protein’s function to some degree by competing with

the substrate, decreasing efficacy and potentially leading to selectivity issues.

Other treatments such as enzyme replacement therapy, or ERT, in which new functional enzymes are infused into the patient, are not suitable for treating neurological conditions because currently available ERTs cannot cross the blood-brain barrier.

Gene therapy, which aims to replace mutated genes with non-mutated genes that then can express functional enzymes, is not readily accepted for treating neurological conditions because the procedure is invasive in nature and the efficacy of treating

neurological conditions remains to be established.

In addition, clinical development, manufacturing and commercialization of gene therapies remains challenging in light of safety risks, complex manufacturing processes and high production costs, and difficulties in establishing prices acceptable to payors and health care systems.

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GCase Enzyme-Related Neurodegenerative Diseases and LSDs

GCase is a lysosomal enzyme encoded by the GBA1 gene that is needed to break down fatty substrates, in particular glucosylceramide and glucosylsphingosine, into sugar and fat.

GCase is a lysosomal enzyme encoded by the GBA1 gene that is needed to break down fatty substrates, in particular glucosylceramide and glucosylsphingosine, into sugars and lipids.

If GCase is dysfunctional or not available at sufficient levels, these fatty substrates start to accumulate and eventually become directly toxic to the cells, as well as initiating a disease cascade including lysosomal and mitochondrial dysfunction and accumulation of aggregated proteins associated with neurodegenerative diseases such as alpha synuclein and phospho-tau leading to neuroinflammation and neuronal cell death.

Our clinical-stage lead product candidate GT-02287 has been shown to restore enzymatic function of GCase in the lysosome, which may be useful as a treatment for Parkinson’s disease, or PD, Gaucher disease, oGD, an LSD, and other neurodegenerative diseases, including dementia with Lewy bodies and Alzheimer’s disease.

Our clinical-stage lead product candidate GT-02287 has been shown to restore enzymatic function of GCase in the lysosome, which may be useful as a treatment for Parkinson’s disease, or PD, Gaucher disease, or GD, an LSD, and other neurodegenerative diseases, including dementia with Lewy bodies and Alzheimer’s disease.

Overview of GBA1 Parkinson’s Disease

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It is widely accepted that GCase deficiency has a biological role as a modifier or facilitator of Parkinson’s disease pathogenesis in the brain.

Brain autopsy studies have shown that decreased levels of GCase are also found in patients with idiopathic Parkinson’s disease (without GBA1 mutations).

Brain autopsy studies have shown that

decreased levels of GCase are also found in patients with idiopathic Parkinson’s disease (without GBA1 mutations).

Reduced GCase activity may enhance the risk for Parkinson’s disease by facilitating a pathological hallmark, namely aggregated alpha-synuclein accumulation.

Aggregated alpha-synuclein accumulation and GCase deficiency are thought to act in a debilitating cycle.

GCase deficiency can cause the accumulation of glucosylceramide and glucosylsphingosine substrates, which has been reported to directly affect the accumulation and aggregation of alpha-

GCase deficiency can cause the accumulation of glucosylceramide and glucosylsphingosine substrates, which has been reported to directly affect the accumulation and aggregation of alpha-synuclein.

In addition, increased aggregated alpha-synuclein levels can lead to less GCase activity, which in turn can lead to more aggregated alpha-synuclein accumulation.

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In Alzheimer’s disease, the main pathophysiology involves the development of amyloid plaques and neurofibrillary tangles which contain aggregated amyloid beta and Tau protein, respectively.

Lysosomal dysfunction has been shown to play a role in aggregation of Tau and development of amyloid plaques.

Lysosomal dysfunction

has been shown to play a role in aggregation of Tau and development of amyloid plaques.

GT-02287 has been shown to reduce tau hyperphosphorylation in response to aggregated amyloid-beta and neuronal cell death in response to aggregated tau in preclinical models.

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These effects on disease markers were accompanied by a dose-dependent behavioral effect shown by improved neuromotor strength as measured by the wire hang test and increased coordination as measured by the beam walk test as well as an improvement in nest building which is a complex behavior involving an element of cognitive function.

Withdrawal of the compound resulted in a reduction in GCase activity as expected but improvement in disease markers and on motor and cognitive function were maintained for at least 9 days, suggesting a disease slowing effect of GT-02287.

Withdrawal of the compound resulted in a reduction in GCase activity as expected but improvement in disease markers and motor and cognitive function were maintained for at least 9 days, suggesting a disease slowing effect of GT-02287.

Nonclinical Toxicology and Safety Studies

The sub-chronic GLP general toxicity studies in both rodents and non-rodents were successfully completed in the second quarter of 2024, without any delays, which allows for the treatment of patients over a three-month period.

To further advance our clinical development plan for GT-02287, we initiated a chronic toxicity study—lasting six months in rodents and nine months in non-rodents during the second half of 2024.

This will enable clinical studies involving GT-02287 in patients for treatment durations exceeding twelve months.

The in-vivo phase of the chronic toxicity study in rodents was completed in February 2025, and the final quality assurance audited report is anticipated by May 2025.

The completion of the in-vivo phase in non-rodent species is expected by the second quarter of 2025.

Additionally, a comprehensive mass-balance study using radiolabeled GT-02287 in rats was concluded in 2024, demonstrating the distribution of the compound within the central nervous system.

Clinical Study

In September 2023, we initiated the first-in-human Phase 1 clinical trial to assess the safety, tolerability, pharmacokinetics, and food effect of GT-02287 in healthy participants.

The study design included a single ascending

dose part during which the study participants receive one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which the study participants received one daily dose of GT-02287 for 14 days at different dose levels.

The study was completed in July 2024 and the quality assurance audited interim report was finalized in the third quarter of 2024.

In the ongoing Phase 1b study, participants with Parkinson’s disease will receive GT-02287 for a period of three months to evaluate safety, tolerability, pharmacokinetics, and the effect of GT-02287 on certain biomarkers of the GCase disease cascade

Nonclinical general chronic toxicity studies in rodent and non-rodent species, with 6- and 9-month administration of GT-02287 respectively, have been completed, enabling clinical dosing beyond 12 months.

Clinical Studies

As of December 31, 2025, two clinical studies of GT-02287 have been completed, and one is ongoing.

GT-02287 was initially characterized in a first-in-human Phase 1a clinical study to assess the safety, tolerability, pharmacokinetics, and food effect of GT-02287 in healthy participants.

The study design included a single ascending dose part during which the study participants received one dose of GT-02287 at different dose levels, and a multiple ascending dose part during which the study participants received one daily dose of GT-02287 for 14 days at different

The Phase 1a study was initiated in September 2023 and was completed in July 2024 and the quality assurance audited interim report was finalized in the third quarter of 2024.

In the second quarter of 2025, a Phase 1 relative bioavailability study in healthy volunteers was initiated.

The purpose of this study was to compare two oral formulations of GT-02287.

This study was completed in the third quarter of 2025.

In March 2025, we enrolled the first participant with Parkinson’s disease in our two-part Phase 1b safety and tolerability study to further evaluate the safety, tolerability and biomarker evidence of activity for GT-02287.

In Part 1 of this study, participants dose daily with GT-02287 for 90 days.

In August 2025, we amended the Phase 1b clinical study to include an additional nine (9) months of daily oral administration of GT-02287 in the optional Part 2 of the Phase 1b.

Participants enrolled in the Phase 1b are also followed for clinical signs of worsening or improvement.

Through September 2025 a total of 21 patients were enrolled in the Phase 1b.

Samples of cerebrospinal fluid were taken at the initiation of dosing and at day 90 following completion of Part 1, and blood samples were taken at multiple timepoints.

In November 2025 a total of 19 patients had completed Part 1 of the Phase 1b and we will be presenting the full analysis of Part 1 throughout 2026.

Of the 19 patients who completed Part 1 of the Phase 1b, a total of 16 patients elected to continue on daily oral administration of GT-02287.

We expect to complete Part 2 of the Phase 1b study in September 2026.

Pipeline Programs in Research and Discovery Phases

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Collaboration and Licensing Arrangements

In connection with our business development activities, we enter into collaborative and licensing arrangement with third parties to use our Magellan™ drug discovery platform to discover novel allosteric sites on proteins and identify proprietary small molecules that bind these sites to disrupt or restore protein function as may be needed to treat a particular disease.

We expect to continue to identify and evaluate collaboration, co-development and licensing opportunities that may be similar to or different from the collaborations and licenses that we have entered into.

We routinely evaluate business development opportunities for the advancement of our lead program, GT-02287, our earlier stage pipeline, and our Magellan TM computational platform technology, including potential licensing, co-development, commercialization, and other strategic alternatives.

These discussions may involve pharmaceutical companies, biotechnology companies, or other strategic partners.

While we continue to assess opportunities that could enhance shareholder value and support the advancement of our development programs, there can be no assurance that any such discussions will result in the execution of a definitive agreement.

We intend to pursue transactions that we believe align with our strategic objectives, strengthen our financial position, and accelerate the development and potential commercialization of our lead candidate.

Minoryx Therapeutics, S.L.

We have entered into a license agreement, dated December 20, 2017 (the “Minoryx License Agreement”), with Minoryx Therapeutics, S.L., a company organized under the laws of Spain (“Minoryx”), pursuant to which we obtained exclusive worldwide license rights from Minoryx to use and exploit its intellectual property (“IP”), including certain components of its computational drug discovery platform Magellan™ for the identification of non-competitive pharmacological chaperones and exclusive worldwide sublicense rights to certain IP licensed by Minoryx from the University of Barcelona and the Institució Catalana de Recerca i Estudis Avançats.

sell, have sold, copy, modify, perform, display, create derivative versions of products in the licensed field or otherwise to exploit Minoryx’s IP in the field.

We entered into a license agreement, dated December 20, 2017 (the “Minoryx License Agreement”), with Minoryx Therapeutics, S.L., a company organized under the laws of Spain (“Minoryx”), pursuant to which we obtained exclusive worldwide license rights from Minoryx to use and exploit its intellectual property (“IP”), including certain components of its computational drug discovery platform Magellan™ for the identification of non-competitive pharmacological chaperones and exclusive worldwide sublicense rights to certain IP licensed by Minoryx from the Universitat de Barcelona and the Institució Catalana de Recerca i Estudis Avançats.

Under the terms of the Minoryx License Agreement, we have an exclusive, worldwide, royalty-bearing, assignable, transferable license, including the right to license through multiple tiers of sublicense, to Minoryx’s IP to make, have made, use, import, export, offer to sell, have sold, copy, modify, perform, display, create derivative versions of products in the licensed field or otherwise to exploit Minoryx’s IP in the field.

Minoryx’s IP includes certain components of the Magellan™ drug discovery platform, certain proprietary Minoryx compounds acting as pharmacological chaperones, all patents and pending applications related thereto and Minoryx’s Know-How.

We also have an exclusive, worldwide, royalty-bearing, assignable, transferable sublicense, including the right to sublicense through multiple tiers of sublicense, to the IP of Universitat de Barcelona (UB) and Institucio Catalana de Recerca i Estudis Avancats (ICREA) in EP11380102 and know-how and software related thereto, for the purpose of making, having made, using, importing, offering to sell, selling and having sold, copying, modifying, performing, displaying, and creating derivative versions of products in the field.

We also have an exclusive, worldwide, royalty-bearing, assignable, transferable sublicense, including the right to sublicense through multiple tiers of sublicense, to the IP of Universitat de Barcelona (UB) and Institució Catalana de Recerca i Estudis Avançats (ICREA) in EP11380102 and know-how and software related thereto, for the purpose of making, having made, using, importing, offering to sell, selling and having sold, copying, modifying, performing, displaying, and creating derivative versions of products in the field.

Under the Minoryx License Agreement, products include any product in the field that would infringe the UB/ICREA IP or the Minoryx IP in the absence of the license provided therein.

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We strive to protect and enhance the proprietary technologies, inventions and improvements that we believe are important to our business, including seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties.

Our policy is to seek to protect our proprietary position by, among other methods, pursuing and obtaining patent protection in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements, platforms and our product candidates that are important to the development and implementation of our business.

As of February 2025, our patent portfolio consisted of two patents granted in the U.S., Europe, and Japan.

three international PCT applications in national phase stage, two international PCT applications published in 2024 and entering national phase in 2025, and two international PCT applications to be published in 2025.

Our policy is to seek to protect our proprietary position by, among other methods, pursuing and obtaining patent protection in the United States and in jurisdictions outside of the United States

related to our proprietary technology, inventions, improvements, platforms and our product candidates that are important to the development and implementation of our business.

As of February 2026, our patent portfolio consisted of two patent families granted in the U.S., Europe, and Japan, four international PCT applications in national phase stage (with patents granted in Japan, China, and Canada), two international PCT applications published in 2025 and entering national phase in 2026, and a provisional application to be converted to an international PCT application and published in 2026.

In regard to our computational drug discovery platform Magellan™, we in-licensed the European patent under the Minoryx License Agreement, which is owned by UB/ICREA and has claims directed to a method of binding site and binding energy determination by mixed explicit solvent simulations.

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Before testing any drug in humans, the product candidate must undergo rigorous preclinical testing.

Preclinical studies include laboratory evaluations of drug chemistry, formulation and stability, as well as in vitro and animal studies to assess safety, and in some cases, to establish the rationale for therapeutic use.

Preclinical studies include laboratory evaluations of drug chemistry, formulation and stability, as well as in vitro and

animal studies to assess safety, and in some cases, to establish the rationale for therapeutic use.

The conduct of preclinical studies is subject to federal and state regulations and requirements, including GLP requirements for safety/toxicology studies.

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Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trial are minimized and are reasonable in relation to the anticipated benefits.

The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until

The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed.

The FDA, the IRB or the sponsor may suspend or discontinue a clinical trial at any time on various grounds, including a finding that the patients are being exposed to an unacceptable health risk.

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Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Special Protocol Assessment

The FD&C Act directs the FDA to meet with sponsors, pursuant to a sponsor’s written request, for the purpose of reaching an agreement on the design and size of clinical trials intended to form the primary basis of an efficacy claim in an NDA or a Biologic Licensing Application (BLA).

If an agreement is reached, the FDA will reduce the agreement to writing and make it part of the administrative record.

This agreement is called a special protocol assessment (SPA).

While the FDA’s guidance on SPAs states that documented SPAs should be considered binding on the review division, the FDA has latitude to change its assessment if certain exceptions apply.

Exceptions include public health concerns emerging that were unrecognized at the time of the protocol assessment, identification of a substantial scientific issue essential to the safety or efficacy testing that later comes to light, a sponsor’s failure to follow the protocol agreed upon or the FDA’s reliance on data, assumptions or information that are determined to be wrong.

Disclosure of Clinical Trial Information

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A single trial may be sufficient in some instances, including (i) where the study is a large multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible or (ii) when there is one adequate and well-controlled clinical investigation plus other confirmatory evidence.

Under the goals and polices agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA, the FDA targets ten months from the filing date to complete its initial review of a new molecular entity NDA and respond to the applicant and six months from the filing date of a new molecular entity NDA for priority review.

molecular entity NDA for priority review.

The FDA does not always meet its PDUFA goal dates for standard or priority NDAs and the review process is often extended by FDA requests for additional information or clarification.

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Competitors, however, may receive approval of different therapeutic agents for the indication for which the orphan product has exclusivity or obtain approval for the same therapeutic agent for a different indication than that for which the orphan product has exclusivity.

Orphan product exclusivity could block the approval of one of our products for

seven years if a competitor obtains approval for the same therapeutic agent for the same indication before we do unless we are able to demonstrate that our product is clinically superior.

Orphan product exclusivity could block the approval of one of our products for seven years if a competitor obtains approval for the same therapeutic agent for the same indication before we do unless we are able to demonstrate that our product is clinically superior.

If an orphan designated product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan exclusivity.

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The FDA may withdraw approval of a drug or indication approved under Accelerated Approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product.

In addition, unless otherwise informed by the FDA, the FDA currently requires, as a condition for Accelerated Approval, that all advertising and promotional materials that are intended for dissemination or publication within 120 days following marketing approval be submitted to the agency for review during the pre-approval review period, and that after 120 days following marketing approval, all advertising and promotional materials must be submitted at least 30 days prior to the intended time of initial dissemination or publication.

period, and that after 120 days following marketing approval, all advertising and promotional materials must be submitted at least 30 days prior to the intended time of initial dissemination or publication.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or the time period for FDA review or approval may not be shortened.

Furthermore, Fast Track designation, Breakthrough Therapy designation, Priority Review and Accelerated Approval do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval, but may expedite the development or review process.

Pediatric Information

Under the Pediatric Research Equity Act of 2003, a New Drug Application (“NDA”), Biologics License Agreement (“BLA”) or supplement to an NDA or BLA must contain data that is adequate to assess the safety and effectiveness of the drug or biological product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements.

Under the Food and Drug Administration Safety and Innovation Act, or FDASIA, the FDA has additional authority to take action against manufacturers not adhering to pediatric study requirements.

Unless otherwise required by regulation, the pediatric data requirements do not apply to products with orphan drug designation.

Patent Term Restoration

Depending upon the timing, duration, and specifics of the FDA approval of the use of our current and potential product candidates, some of our U.S.

patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984 ("Hatch-Waxman Amendments").

The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.

However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of an NDA or BLA plus the time between the submission date of the NDA or BLA and the approval of that application.

Only one patent applicable to an approved biological product is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent.

Patent and Trademark Office (“PTO”), in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

Post-Approval Requirements for Drugs

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For example, the FDA may require post-market testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

In addition, drug manufacturers and their subcontractors involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic, unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP.

periodic, unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP.

These impose certain procedural and documentation requirements upon us and our contract manufacturers.

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Manufacturing, sales, promotion and other activities of product candidates following product approval, where applicable, or commercialization are also subject to regulation by numerous regulatory authorities in the U.S.

addition to the FDA.

in addition to the FDA.

These authorities may include the Centers for Medicare & Medicaid Services, or CMS, other divisions of the Department of Health and Human Services, the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency and state and local governments and governmental agencies.

Healthcare Reform

The containment of health care costs is a priority of federal, state and foreign governments, and the prices of drugs have been a focus in this effort.

In March 2010, Congress passed the Affordable Care Act, or the ACA, a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of health spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional policy reforms.

The ACA, for example, contains provisions that subject products to potential competition by lower-cost products and may reduce the profitability of products through increased rebates for drugs reimbursed by Medicaid programs, addresses a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increase the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extends the rebate program to individuals enrolled in Medicaid managed care organizations;

establish annual fees and taxes on manufacturers of certain branded prescription drugs;

and create a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (increased to 70% pursuant to the Bipartisan Budget Act of 2018, or BBA, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D.

Since its enactment, there have been judicial, administrative, executive and Congressional legislative challenges to certain aspects of the ACA.

We expect that there will be additional challenges and amendments to the ACA in the future.

For example, on June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.

In addition, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (“IRA”) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

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 any additional challenges and healthcare reform measures of the Trump administration will impact the ACA and our business.

Other federal health reform measures have been proposed and adopted in the U.S.

since the ACA was enacted:

● The Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.

A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.

These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments to the statute, including the BBA, will remain in effect through 2031, unless additional Congressional action is taken.

Under current legislation the actual reduction in Medicare payments will vary from 1% in 2022 to up to 4% in the final fiscal year of this sequester.

● The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

● The Middle Class Tax Relief and Job Creation Act of 2012 required that CMS reduce the Medicare clinical laboratory fee schedule by 2% in 2013, which served as a base for 2014 and subsequent years.

● In addition, effective January 1, 2014, CMS also began bundling the Medicare payments for certain laboratory tests ordered while a patient received services in a hospital outpatient setting.

Further, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products which have resulted in several recent Congressional inquiries and proposed and enacted bills designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.

In addition, the U.S.

government, state legislatures and foreign governments have shown significant interest in implementing cost containment programs, including price-controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs to limit the growth of government paid healthcare costs.

For example, the U.S.

government has passed legislation requiring pharmaceutical manufacturers to provide rebates and discounts to certain entities and governmental payors to participate in federal healthcare programs.

In addition, the IRA, among other things, (i) directs the U.S.

Department of Health and Human Services (“HHS”) to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” for such drugs and biologics under the law, and (ii) imposes rebates with respect to certain drugs and biologics covered under Medicare Part B or Medicare Part D to penalize price increases that outpace inflation.

The IRA permits HHS to implement many of these provisions through guidance as opposed to regulation for the initial years.

These provisions will progressively take effect beginning in fiscal year 2023, although they may be subject to legal challenges.

It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

Further, the Biden administration released an additional executive order on October 14, 2022 directing HHS to submit a report on how the Center for Medicare and Medicaid (“CMS”) Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.

It is unclear whether this executive order or similar policy initiatives will be implemented in the future.

Individual states in the U.S.

have also been increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological 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.

From time to time legislation is drafted, introduced and passed in Congress that could significantly change the statutory provisions governing the sale, marketing, coverage and reimbursement of products regulated by CMS or other government agencies.

In addition to new legislation, CMS regulations and policies are often revised or interpreted by the agency in ways significantly affecting our business and our products.

Legislative and Regulatory Changes, Including Health Care Reform

The laws and regulation that affect our business are subject to change from time to time, and entirely new laws and regulations are sometimes adopted.

In particular, healthcare reforms that have been adopted, and that may be adopted in the future, could result in further reductions in coverage and levels of reimbursement for pharmaceutical products, increases in rebates payable under U.S.

government rebate programs and additional downward pressure on pharmaceutical product prices.

In 2022, President Biden signed the Inflation Reduction Act, which, among other things, contains a provision that authorizes CMS to negotiate a "maximum fair price" for a limited number of high-cost, single-source drugs each year, and another provision that requires drug companies to pay rebates to Medicare if prices rise faster than inflation.

It is unclear to what extent these and other statutory, regulatory, and administrative initiatives will be enacted and implemented in future years.

Other Healthcare Laws and Regulations

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These laws may impact, among other things, our proposed sales and marketing strategies.

In addition, we may be subject to patient privacy regulations by both the federal government and the states in which we conduct our business.

In addition, we may be subject to patient privacy regulations by both the federal government

and the states in which we conduct our business.

These laws include, without limitation, state and federal anti-kickback, fraud and abuse, false claims, privacy and security and physician sunshine laws and regulations.

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Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims.

The federal government continues to use the FCA and the accompanying threat of significant liability in its investigations and

prosecutions of pharmaceutical and biotechnology companies throughout the U.S.

The federal government continues to use the FCA and the accompanying threat of significant liability in its investigations and prosecutions of pharmaceutical and biotechnology companies throughout the U.S.

Such investigations and prosecutions frequently involve, for example, the alleged promotion of products for unapproved uses and other sales and marketing practices.

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As noted above, analogous state laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors including private insurers.

Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.

Some state laws require pharmaceutical companies to

comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.

There are also state and local laws that require the registration of pharmaceutical sales representatives.

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If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

Ensuring business arrangements comply with applicable healthcare

laws, as well as responding to possible investigations by government authorities, can be time- and resource consuming and can divert a company’s attention from the business.

Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and resource consuming and can divert a company’s attention from the business.

Data Privacy and Security

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To obtain a Marketing Authorization, or MA, for a product in the EEA, for example, an applicant must be established within the EEA.

authorities in the EEA countries (decentralized procedure, national procedure or mutual recognition procedure).

The applicant must submit a Marketing Authorization Application, or MAA, either under a centralized procedure administered by the European Medicines Agency (the “EMA”) or one of the procedures administered by competent authorities in the EEA countries (decentralized procedure, national procedure or mutual recognition procedure).

The centralized procedure provides for the grant of a single MA by the European Commission that is valid for all EEA countries.

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PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet medical needs.

a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.

Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicinal product will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.

Benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements and potentially accelerated MAA assessment once a dossier has been submitted.

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Upon grant of a MA in the EEA, innovative medicinal products generally benefit from eight years of data exclusivity and an additional two years of market exclusivity.

If granted, data exclusivity prevents generic or biosimilar applicants from referencing the innovator's pre-clinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization during a period of eight years from the date on which the reference product was first authorized in the EEA.

on which the reference product was first authorized in the EEA.

During the additional two-year period of market exclusivity, a generic or biosimilar marketing authorization can be submitted, and the innovator's data may be referenced, but no generic or biosimilar product can be marketed until the expiration of the market exclusivity period.

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Similar to the United States, both MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the European Commission and/or the competent regulatory authorities of the individual EEA countries.

The holder of an MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance who is responsible for oversight of that

The holder of an MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance who is responsible for oversight of that system.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.

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An orphan product can also benefit from an additional two years of market exclusivity in the EU for pediatric studies.

The ten-year market exclusivity period may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity.

of market exclusivity.

Additionally, marketing authorization may be granted to a similar product for the same indication at any time if (i) the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior;

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A harmonized procedure for the assessment of applications for clinical trials has been introduced and is divided into two parts.

Part I assessment is led by the competent authorities of a reference Member State selected by the trial sponsor and relates to clinical trial aspects that are considered to be scientifically harmonized across EU

Member States.

This assessment is then submitted to the competent authorities of all concerned Member States in which the trial is to be conducted for their review.

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The MHRA has been updating various aspects of the regulatory regime for medicinal products in the UK.

These include introducing the Innovative Licensing and Access Procedure to accelerate the time to market and facilitate patient access for innovative medicinal products, updates to the UK national approval procedure, introduction of a 150-day objective for assessing applications for marketing authorizations in the UK, Great Britain and Northern Ireland and a rolling review process for marketing authorization applications (rather than a consolidated full dossier submission).

UK, Great Britain and Northern Ireland and a rolling review process for marketing authorization applications (rather than a consolidated full dossier submission).

Orphan designation in Great Britain following Brexit is, unlike in the EU, not available pre-marketing authorization.

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Employees and Human Capital Resources

As of December 31, 2024, we had twenty-three full-time employees and two part-time employees.

Of these twenty-five employees, seventeen were engaged in research and development activities and eight were engaged in finance, business development, administrative support and general management.

As of December 31, 2025, we had 20 full-time employees and one part-time employee.

Of these 21 employees, 13 were engaged in research and development activities and eight were engaged in finance, business development, administrative support and general management.

We have a branch office in Barcelona, Spain.

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Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.

We maintain our equity incentive plan in order to attract, retain and incentivize our workforce through the granting of stock-based compensation.

We maintain our equity

incentive plan in order to attract, retain and incentivize our workforce through the granting of stock-based compensation.

We also provide cash bonus awards based on company progress toward key annual goals and employee performance.

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You can review our electronically filed reports and other information that we file with the SEC on the SEC’s web site at http://www.sec.gov.

In addition, we regularly use our website to post information regarding our business, product

development programs and governance, and we encourage investors to use our website, specifically the section titled “Investor Relations” as a source of information about us.

In addition, we regularly use our website to post information regarding our business, product development programs and governance, and we encourage investors to use our website, specifically the section titled “Investors & Media” as a source of information about us.

The information on our website is not incorporated by reference into this Annual Report and should not be considered to be part of this Annual Report.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business