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Item 1. Business

2026-02-27 compared with 2025-03-06 · 134 added, 221 removed, 345 unchanged (51% of the section changed)

ITEM 1 - BUSINESS

We are a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need.

We are a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat inflammatory and immune-mediated conditions with high unmet need.

We have exclusive worldwide rights to research, develop and commercialize products containing small molecule bromodomain and extra-terminal domain (“BET”) inhibitors for the treatment of any disease, disorder or condition in humans, which we licensed from Tay Therapeutics Ltd., formerly known as In4Derm Ltd ("Tay").

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Through our transaction with Tay, we obtained access to a library of new small molecule BET inhibitor compounds including those that inhibit both BD1 and BD2 (“pan-BD” BET inhibitor) and that selectively inhibit BD2 (“BD2-selective” BET inhibitor).

Through our access to this library of new BET inhibitors, which comprise our InhiBET™ portfolio, we plan to develop product candidates for a diverse set of therapeutic indications.

We have chosen to initially focus our development efforts with these molecules on immune-mediated inflammatory diseases, which are not being targeted by current BET inhibitors in development.

Our lead program is repibresib gel (also known as VYN201 ), a topically administered, small molecule pan-BD BET inhibitor designed as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure.

In preclinical testing, repibresib produced consistent reductions in pro-inflammatory and disease-related biomarkers and improvements in disease severity across a variety of inflammatory and fibrotic preclinical models.

In November 2022, we initiated a Phase 1 clinical trial evaluating a topical formulation of repibresib first in healthy volunteers (Phase 1a) and then in subjects (Phase 1b) with nonsegmental vitiligo (NSV), an immune-mediated condition that has a high unmet need and only one approved therapy.

In the first quarter of 2023, we announced positive preliminary safety and tolerability, including hematology data, and predicted pharmacokinetic results (minimal systemic exposures) from the Phase 1a portion of the trial .

We initiated the Phase 1b portion of the trial in NSV subjects in January 2023 and announced positive data from the Phase 1b trial in October 2023.

We showed significant clinical improvements in vitiligo involving the face, which has the greatest psychosocial impact on patients, after 16 weeks of treatment using the Facial-Vitiligo Area Scoring Index ("F-VASI").

We initiated a Phase 2b trial with repibresib ge l in NSV subjects in June 2024.

The Phase 2b trial is a randomized, double-blind, vehicle-controlled trial evaluating the efficacy, safety and pharmacokinetics of once-daily repibresib gel in NSV subjects in three dose cohorts (1%, 2% or 3% concentrations) compared to vehicle over 24 weeks, followed by a 28-week active treatment extension with subjects on vehicle crossing over to active doses.

We enrolled approximately 45 patients in each arm and expect to report top-line results from the 24-week double-blind portion of the trial in mid-2025.

Our second program is VYN202, an oral, small molecule BD2-selective BET inhibitor.

We initially focused our development efforts with these molecules on immune-mediated inflammatory diseases, which are not being targeted by current BET inhibitors in development.

In August 2025, we initiated a strategic review to evaluate a range of options to maximize stockholder value, including the assessment of our internal pipeline, financing opportunities and strategic alternatives.

As part of this process, we evaluated opportunities for repibresib and VYN202, including as part of broader strategic alternatives.

In conjunction, we implemented cost reductions to extend our cash runway.

Following the strategic review, we entered into an Agreement and Plan of Merger and Reorganization, dated as of December 17, 2025, which was amended on January 30, 2026 (as amended, the "Merger Agreement") with Yarrow Biosciences, Inc.

("Yarrow"), pursuant to which, among other matters, Yellow Merger Sub Corp., a direct, wholly owned subsidiary of ours ("Merger Sub"), will merge with and into Yarrow, with Yarrow surviving as a wholly owned subsidiary of VYNE and the surviving corporation of the merger (the "Merger").

In connection with the Merger, VYNE will change its name to “Yarrow Bioscience, Inc.” VYNE following the Merger is referred to herein as the “Combined Company.” The Merger is intended to qualify for federal income tax purposes as (1) a tax-free reorganization under the provisions of Section 368(a) of the Internal Revenue Code of 1986, as amended (the "Code") and/or (2) an exchange of shares of Yarrow stock for VYNE common stock under Section 351(a) of the Code.

Following completion of the Merger, the Combined Company plans to focus on advancing YB-101 (also known as GS-098), a clinical-stage, potentially first-in-class TSHR antibody for the treatment of Graves Disease and explore a clinical development plan for the treatment of Thyroid Eye Disease.

We may continue to evaluate opportunities for repibresib and VYN202, which may include a sale, license, transfer, disposition, divestiture or other monetization transaction to a third party or to a related party so long as the transaction would not result in material post-closing obligations to us without Yarrow’s consent.

If the Merger Agreement is terminated, we may pursue other strategic alternatives, including financing opportunities, or liquidation.

The Proposed Merger and Special Cash Dividend

At the effective time of the Merger, (i) each then-outstanding share of Yarrow common stock, par value $0.0001 per share and Yarrow Series A Preferred Stock, par value $0.0001 per share, including any shares of Yarrow common stock or Yarrow pre-funded warrants issued in the Yarrow Pre-Closing Financing described below, will be converted into the right to receive a number of shares of VYNE common stock, par value $0.0001 per share or VYNE pre-funded warrants (as described below) equal to an exchange ratio calculated in accordance with the Merger Agreement (the "Exchange Ratio"), (ii) each then outstanding Yarrow option to purchase shares of Yarrow common stock will be converted into and become an option to purchase shares of VYNE common stock on the existing terms and conditions, subject to adjustment as set forth in the Merger Agreement, and (iii) each then-outstanding and unexercised pre-funded warrant to purchase shares of Yarrow common stock will be converted into a pre-funded warrant to purchase shares of VYNE common stock on the existing terms and conditions, subject to adjustment as set forth in the Merger Agreement and the form of pre-funded warrant.

In connection with the Merger, certain institutional investors led by an affiliate of RTW Investments purchased $100 million of Yarrow Series A Preferred Stock in a private placement and have agreed to purchase, prior to the closing of the Merger, an additional $100 million of Yarrow's common stock and/or pre-funded warrants, in a "Pre-Closing Financing" that will convert into VYNE common stock or VYNE pre-funded warrants at the closing of the Merger, in accordance with the Merger Agreement.

Each share of VYNE common stock that is issued and outstanding at the effective time of the Merger will remain issued and outstanding and such shares, subject to a proposed reverse stock split, will be unaffected by the Merger.

Prior to the effective time, options to purchase shares of VYNE common stock and any VYNE restricted stock units will be accelerated.

Any "in-the-money" options will be cancelled and cashed out;

any "out-of-the-money" options will be cancelled for no consideration.

Under the terms of the Merger Agreement, the pre-Merger VYNE stockholders are expected to own approximately 3% of the Combined Company, and the pre-Merger Yarrow stockholders (inclusive of those investors who participated in Yarrow's Series A Preferred Financing and who will participate in Yarrow's Pre-Closing Financing, described above) are expected to own approximately 97% of the Combined Company, which is subject to adjustment in accordance with the Merger Agreement.

In addition, in connection with the closing of the Merger, we expect to declare a special cash dividend to our pre-Merger stockholders and warrant holders of approximately $14.5 million to $16.5 million in the aggregate, subject to adjustment as set forth in the Merger Agreement.

Our BETi Platform and Product Candidates to Date

Our former lead program is repibresib gel (also known as VYN201 ), a topically administered, small molecule pan-BD BET inhibitor designed as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure.

We initiated a Phase 2b trial with repibresib ge l in nonsegmental vitiligo ("NSV") subjects in June 2024.

The Phase 2b trial was a randomized, double-blind, vehicle-controlled trial evaluating the efficacy, safety and pharmacokinetics of once-daily repibresib gel in NSV subjects in three dose cohorts (1%, 2% or 3% concentrations) compared to vehicle over 24 weeks, followed by a 28-week active treatment extension with subjects on vehicle crossing over to active doses.

In July 2025, VYNE announced that the trial did not meet its primary endpoint of the proportion of subjects achieving an improvement in Facial Vitiligo Area Scoring Index of at least 50% from baseline (“F-VASI50”) at week 24 compared to vehicle.

Based on these data, VYNE discontinued the then ongoing extension phase of the trial and terminated the trial.

We are currently developing VYN202, an oral, small molecule BD2-selective BET inhibitor.

Prior studies have shown that while BD1 modulates cell-cycling and homeostatic functions, BD2 regulates gene expression of pro-inflammatory mediators in cells.

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By maximizing BD2 selectivity, we believe VYN202 has the potential to be a potent oral immunomodulator option for both acute control and chronic management of immune-mediated inflammatory conditions, without the hematologic and gastrointestinal adverse effects associated with earlier generation systemic pan-BD BET inhibitors that were being developed in oncologic settings.

We have completed a Phase 1a single ascending dose/multiple ascending dose ("SAD/MAD") trial of VYN202 in healthy volunteers and announced positive data from this trial in December 2024.

We observed that VYN202 had a favorable safety and tolerability profile with no drug-related adverse events historically associated with earlier generation, less BD2-selective BET inhibitors.

VYN202 also demonstrated robust pharmacodynamic activity including evidence of target engagement and inhibition of several inflammatory biomarkers relevant to immune-mediated disorders in ex vivo stimulation assays.

We initiated a Phase 1b trial in February 2025 in adult subjects with moderate-to-severe plaque psoriasis.

The Phase 1b trial is a randomized, double-blind, placebo-controlled trial of once daily treatment with VYN202 capsules dosed for 12 weeks, to primarily evaluate the safety of VYN202 across four cohorts (0.25 mg, 0.5 mg, 1 mg doses and placebo), with secondary objectives that include pharmacokinetics and preliminary evidence of efficacy via endpoints evaluating improvements from baseline in psoriasis area and severity index (PASI) scores.

The trial will also include a 4-week safety follow-up visit after completion of the 12-week dosing period.

We expect to enroll approximately 80 subjects with moderate-to-severe plaque psoriasis and to report top-line results from the placebo-controlled trial by the end of 2025.

Additionally, we anticipate that the data from the Phase 1b trial in plaque psoriasis subjects will provide key insights into VYN202's potential activity across a range of immune-mediated diseases.

We intend to advance our product candidates through further phases of clinical development toward regulatory approval.

As part of our strategy to maximize the value of our pipeline, we may partner with larger pharmaceutical companies to expand and accelerate the development of our programs and explore other indications and therapeutic areas outside of our core focus in immune-mediated diseases.

The Phase 1b trial was a randomized, double-blind, placebo-controlled trial of once daily treatment with VYN202 capsules dosed for 12 weeks, to primarily evaluate the safety of VYN202 across four cohorts (0.25 mg, 0.5 mg, 1 mg doses and placebo), with secondary objectives that include pharmacokinetics and preliminary evidence of efficacy via endpoints evaluating improvements from baseline in psoriasis area and severity index (PASI) scores.

In April 2025, the FDA verbally placed a clinical hold on our Phase 1b trial following an observation of testicular toxicity in dogs from a non-clinical toxicology study of VYN202.

In June 2025, the FDA lifted the clinical hold for two doses of VYN202 for female subjects.

Further, the FDA indicated that sufficient data from a 12-week non-clinical toxicology study of VYN202 in dogs would be required in order to resume studies in male clinical subjects.

The design of this toxicology study was agreed upon with the FDA.

In July 2025, we made the decision to unblind the clinical data from the seven subjects who were enrolled in the trial (VYN202 treated:

n=6 across 0.25 mg, 0.5 mg and 1 mg doses;

placebo treated:

All subjects treated with VYN202 had an improvement in signs and symptoms of disease, while the subject who received placebo did not.

In addition, the subjects who received VYN202 for greater than one week showed reductions in serum cytokine levels involved in the pathogenesis of plaque psoriasis, while there was no change in this biomarker level for the subject receiving placebo.

Based on this data, together with promising results for VYN202 in multiple preclinical models, we terminated the Phase 1b psoriasis trial in support of continued advancement of VYN202 into other serious, immune-mediated diseases with more limited effective treatment options.

In October 2025, we initiated the repeat non-clinical toxicology study of VYN202 in male dogs to remedy the partial hold in male clinical subjects.

The study is expected to be completed in the second half of 2026, with a final report expected in the fourth quarter of 2026.

BET Proteins:

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The diagram below depicts the role of BET proteins in gene transcription via the NF-kB pathway, and the subsequent effect of disrupting this process on expression of inflammatory cytokines.

Our Platform and Product Candidates

Our BET Inhibitor Platform and Product Candidates

InhiBET™ BET Inhibitor Platform

Through our partnership with Tay, we have exclusive worldwide rights to research, develop and commercialize products containing certain BET inhibitor compounds for the treatment of any disease, disorder or condition in humans.

See "Development and License Agreements—Tay License Agreements." Utilizing our InhiBET platform and through our preclinical and clinical activities, we are evaluating the impact that BET inhibitor compounds have on regulating proinflammatory cytokines.

We are targeting indications whose pathogenesis is linked to excessive production of these cytokines.

We have selected development candidates and are developing formulations that are designed to maximize the anti-inflammatory effect of the drugs while minimizing safety concerns.

Through our InhiBET development platform, we believe we can demonstrate the potential utility of these BET inhibitor compounds and develop therapies for a variety of immune-mediated diseases.

Repibresib - Locally Administered Pan-BD BET Inhibitor

Our lead BET inhibitor candidate in development is repibresib gel, which was developed using the InhiBET platform and is a topically-administered BET inhibitor.

It is a first-in-class “soft” pan-BD BET inhibitor that is being developed to address diseases involving multiple, diverse inflammatory cell signaling pathways.

Our goal with the repibresib program is to develop a therapy that delivers potent, localized anti-inflammatory effects and can be rapidly cleared through the body's metabolic processes to avoid systemic effects.

We have conducted several preclinical studies which have demonstrated repibresib’s anti-fibrotic and anti-inflammatory activities and the ability to significantly reduce the expression of key cytokines relevant to certain autoimmune diseases, including vitiligo, psoriasis, rheumatoid arthritis, and idiopathic pulmonary fibrosis.

In October 2023, we announced positive data from our Phase 1b trial of repibresib gel in subjects with NSV, which demonstrated clinical proof-of-concept for the use of this BET inhibitor to treat an immune-mediated disease.

We initiated a Phase 2b trial with repibresib gel in NSV subjects in June 2024.

Based on data generated to date, we believe repibresib has the potential to be highly versatile across multiple indications by serving as a locally-acting therapy with low systemic exposure.

Nonsegmental Vitiligo (NSV)

Vitiligo is a chronic autoimmune depigmenting disorder of the skin, characterized by the loss of pigment-producing cells known as melanocytes.

Vitiligo is the most common depigmenting skin condition, with a prevalence estimated at 0.5 - 2.0% of the world population.

An article published in the scientific journal, JAMA Dermatology, in 2021 estimated that there were between 1.9 million and 2.8 million cases of vitiligo in the United States.

Approximately 90% of vitiligo cases are characterized as nonsegmental, in which white patches appear symmetrically on both sides of the body.

There is currently only one drug, OPZELURA® (ruxolitinib) cream, approved by the FDA for the treatment of NSV.

That product includes a boxed safety warning on its label.

Based on preclinical and clinical data generated to date, we believe that repibresib gel has the potential to offer a targeted, efficacious, and a safe treatment option for NSV that lowers the disease recurrence rate and can be effective for all skin phototypes with few side effects.

Ph a se 1 Clinical Trial

Based in part on the data we observed from the preclinical vitiligo model described below, we commenced a Phase 1 clinical trial evaluating repibresib topical ointment for the treatment of NSV in November 2022.

The trial was conducted at U.S.-based clinical centers.

In the Phase 1a portion of the trial, single ascending and multiple ascending doses of repibresib were applied topically once daily to 30 healthy volunteers in five dose cohorts for two weeks with a one-week safety follow-up visit to evaluate the safety, tolerability and pharmacokinetics of repibresib.

Evaluated doses included 0.025%, 0.1%, 0.5%, 1.0% and 2.0% concentrations.

There were no serious adverse events and no dose adjustments were required.

There were no clinically-relevant treatment emergent adverse events, abnormal clinical laboratory results or electrocardiogram findings, and no discontinuations.

We selected the 0.5%, 1.0% and 2.0% doses for further evaluation in the Phase 1b portion of the trial.

The Phase 1b portion was a 16-week open-label trial assessing the safety, tolerability and pharmacokinetics of once-daily repibresib in 29 patients across the three dose cohorts.

Exploratory efficacy of repibresib was also evaluated, including its ability to arrest the progression of skin depigmentation and support skin repigmentation in patients with active disease using F-VASI scoring.

In October 2023, we announced positive results from the Phase 1b portion of the trial.

Significant clinical improvement was observed in the 1.0% and 2.0% cohorts with rapid onset of action and a dose-dependent response.

Mean percentage reduction in F-VASI score from baseline after 16 weeks of treatment was 7.5%, 30.2% and 39.0% for the 0.5%, 1.0% and 2.0% cohorts, respectively.

There were no clinically-relevant treatment emergent adverse events in any cohort.

Ph a se 2 Clinical Trial

Last year, we reformulated repibresib in a once-daily gel for our Phase 2b trial in subjects with NSV, which we initiated in the second quarter of 2024.

The ongoing Phase 2b trial is a randomized, double-blinded, vehicle-controlled trial evaluating subjects with NSV for 24 weeks, followed by a separate active treatment extension phase for an additional 28 weeks, with vehicle subjects crossing over to active doses at Week 24.

The trial is evaluating four arms (three active arms, one vehicle arm) of once-daily repibresib gel, with each arm enrolling approximately 45 subjects with active or stable NSV.

The primary efficacy endpoint of the trial is an evaluation of the proportion of subjects achieving F-VASI50 at Week 24 compared to vehicle.

In January 2025, we announced the completion of enrollment in the trial.

We anticipate top-line results from the 24-week double-blind portion of the trial to be available in mid-2025.

Preclinical Studies for Multiple Indications

We conducted a preclinical study using an ex vivo skin model of vitiligo.

The objectives of this study were to evaluate the potential of repibresib to:

• reduce matrix metalloproteinase-9 (“MMP-9”) secretion, which allows for melanocyte stabilization and limits loss of melanocytes/depigmentation in vitiligo;

• reduce the soluble adhesion molecule, E-cadherin, which is a biomarker of melanocyte loss due to degradation of matrix-bound E-cadherin by MMP-9;

• minimize the loss of melanocytes by assessing melanin pigment content;

• increase the expression of genes commonly associated with melanogenesis (melanin synthesis, melanosome maturation and transport).

In the preclinical study, repibresib reduced the expression of key pro-inflammatory biomarkers relevant to the pathogenesis of vitiligo and resulted in marked reduction in melanocyte loss.

Repibresib produced a dose-dependent reduction in MMP-9 and soluble E-cadherin and substantially reduced the loss of melanin pigment in the basal layers of skin at the 0.1% and 1.0% concentrations.

In addition, repibresib significantly upregulated WNT16, a member of the WNT family of genes, suggestive of increased melanogenesis.

The WNT/β-catenin signaling pathway is known to be dysregulated in vitiligo and is believed to play a key role in melanocyte regeneration.

In additional in vitro assays using human CD8+ t-cells with repibresib:

• Repibresib was found to potently inhibit the differentiation of CD8+ T-cells that are known to induce both a cytotoxic and destabilizing effect on melanocytes, the primary cell type that produces melanin in skin.

• Repibresib inhibited the release of interferon-gamma which is a cytokine known to drive differentiation of CD8+ T-cells.

Plaque Psoriasis

We evaluated the impact of repibresib on Th17-mediated inflammation in an established preclinical animal model of psoriasis and an ex vivo human tissue study.

T-helper 17, or Th17, cells are a CD4+ T-cell subset characterized by production of the inflammatory cytokine, interleukin-17, or IL-17.

Th17 cells play an important role in the pathogenesis of a diverse group of immune-mediated diseases, including psoriasis, psoriatic arthritis, inflammatory bowel disease, and multiple sclerosis.

In the animal model, depilated mice were topically dosed with imiquimod cream to induce a psoriasis phenotype over a 7-day induction phase.

A further 7-day treatment phase evaluated three doses of repibresib (0.001%, 0.01% and 0.1% concentrations) compared to a highly potent topical corticosteroid (clobetasol propionate 0.05% cream) used as a positive control, and a vehicle control.

An imiquimod-naive control group (healthy control group) was also included for vehicle treatment.

In these studies, treatment with repibresib significantly reduced the expression of several key proinflammatory cytokines relevant to Th17-mediated autoimmune diseases.

A dose-dependent improvement in the signs of inflammation was observed in repibresib treatment groups, and treatment with repibresib at all concentrations was well tolerated in the study.

Idiopathic Pulmonary Fibrosis

We evaluated an inhaled formulation of repibresib in an established mouse model of idiopathic pulmonary fibrosis.

Lung fibrosis was induced in mice using a single intratracheal dose of bleomycin.

Fibrosis was left to develop for seven days, and thoracic tomography images were obtained to stage fibrotic development.

Animals were assigned to six treatment groups:

untreated and unstimulated control, placebo, and one of four doses of repibresib (0.1, 0.2, 0.5, and 1.0 mg/mL), with six mice in

Each treatment group was dosed intratracheally every other day for 14 days.

Changes in blood oxygen saturation, Ashcroft scoring (a standardized numerical scale used to quantify the extent of lung fibrosis in histological samples), lung hydroxyproline (a tissue biomarker for fibrosis), and volumetric lung function were assessed.

Treatment with repibresib at 0.5 mg/mL and 1 mg/mL resulted in statistically significant reductions in Ashcroft scores and levels of hydroxyproline compared to the placebo control group at Day 21.

In addition, mean blood oxygen saturation for the repibresib 1 mg/mL group was 92.4% at Day 21, an 8.8% improvement compared to the placebo group (83.6%).

Mean blood oxygen saturation for the untreated and unstimulated control group was 95.2%.

Thoracic tomography revealed that repibresib treatment groups experienced a dose-dependent improvement in functional lung volume compared to the placebo control group.

Rheumatoid Arthritis

We conducted a preclinical study showing that intra-articular injections of repibresib resulted in significant inhibition of inflammation in a validated animal model of rheumatoid arthritis.

In the preclinical study, inflammatory arthritis was induced in BALB/c mice.

Each treatment group of seven mice was injected with either (i) an intra-articular dose of vehicle, (ii) an intra-articular dose of repibresib (with one of four concentrations ranging from 0.01 to 10 mg/kg), (iii) an intra-articular dose of dexamethasone (1 mg/kg) or (iv) a systemic dose of dexamethasone (1 mg/kg, via intraperitoneal injection).

The intra-articular doses were administered on days 0, 3, 6 and 9 while the dexamethasone systemic injections were given daily beginning at day 0 through 11.

Each animal treated with the intra-articular injections received the injection in the ankle of one rear paw.

The untreated rear paw was assessed to evaluate any potential anti-inflammatory systemic effect.

Treatment response was evaluated based on an assessment of paw thickening or swelling (in millimeters) and arthritis scoring based on a five-point composite severity scale of redness, swelling of the ankles and wrists, and paw thickness.

Scoring in this model ranges from 0 (normal) to 4 (extensive signs and symptoms of arthritis).

Treatment with repibresib resulted in marked inhibition of paw thickening at the 1 and 10 mg/kg doses.

At both doses, the inhibition of paw thickening was statistically significant in the treated paw relative to the untreated rear paw on Day 12 (p<0.01).

In addition, limbs treated with repibresib at the 1 and 10 mg/kg dose levels had an average arthritis score of 0.57 and 0.67, respectively, or near normal.

The arthritis score was significantly lower in the treated paw at both doses relative to the non-treated paws on Day 12 (p<0.05).

Until July 2025, our lead product was repibresib gel (also known as VYN201), a topically administered, small molecule pan-bromodomain (“BD”) BET inhibitor designed as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure.

We initiated a Phase 2b trial in nonsegmental vitiligo in June 2024.

The trial evaluated 177 subjects (mITT population).

In July 2025, we announced that the trial did not meet its primary endpoint of the proportion of subjects achieving an improvement in Facial Vitiligo Area Scoring Index of at least 50% from baseline (“F-VASI50”) at week 24 compared to vehicle.

Based on these data, we discontinued the ongoing extension phase of the trial and terminated the trial.

Repibresib gel is covered by patents providing composition of matter patent exclusivity into at least 2042 in the United States and into at least 2040 in Europe, Japan and other large global pharmaceutical markets.

We are seeking an external partner for continued development of repibresib gel.

VYN202 - Oral BD2-Selective BET Inhibitor

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Systemic BET inhibitors have historically targeted both BD1 and BD2 less selectively, which we believe caused gastrointestinal toxicity and bone marrow suppressive effects like thrombocytopenia.

By maximizing BD2 selectivity, we believe VYN202 may alleviate the toxicities observed by other less BD2-selective BET inhibitors in development for oncology and have the potential to be a potent, oral immunomodulator option for both acute control and chronic management of immune-mediated conditions, where the damaging effects of unrestricted inflammatory signaling activities are common.

Phase 1a SAD/MAD Clinical Trial

We have completed a Phase 1a SAD/MAD trial of VYN202 in healthy volunteers and announced positive data from this trial in December 2024.

We observed that VYN202 had a favorable safety and tolerability profile with no drug-related adverse events historically associated with earlier generation, less BD-selective BET inhibitors.

In February 2025, we initiated a Phase 1b trial in adult subjects with moderate-to-severe plaque psoriasis.

The Phase 1b trial is a randomized, double-blind, placebo-controlled trial to primarily evaluate the safety of VYN202 administered orally once a day across four cohorts (0.25 mg, 0.5 mg, 1 mg doses and placebo), with secondary objectives that include pharmacokinetics and preliminary evidence of efficacy via endpoints evaluating improvements from PASI scores after 12 weeks.

We expect to enroll approximately 80 subjects with psoriasis and to report top-line results from the placebo-controlled trial by the end of 2025.

Additionally, we anticipate that the data from the Phase 1b trial in psoriasis subjects will provide key insights into VYN202’s potential activity across a range of immune-mediated diseases.

Preclinical Data in Multiple Indications

Plaque Psoriasis

We evaluated VYN202 in an established mouse model of psoriasis that was used earlier with repibresib gel (see above).

After inducing a psoriasis phenotype in BALB/c mice, treatment was administered intraperitoneally with VYN202 doses,

deucravacitinib (an allosteric TYK2 inhibitor approved for the treatment of moderate-to-severe plaque psoriasis), or placebo.

VYN202 and deucravacitinib at equivalent dosing resulted in comparable onset of action and efficacy.

Mice receiving VYN202 3 mg/kg had approximately 95% mean reduction in PASI score from baseline by day 7 of treatment, which was consistent with the results in the deucravacitinib 3 mg/kg group.

Treatment with VYN202 3 mg/kg reduced the expression of IL-17A, a major effector cytokine involved in the pathogenesis of psoriasis, by 93% compared to placebo.

Treatment with VYN202 at all doses also resulted in a marked reduction of other disease-related cytokines (IL-1β, IL-6, IL-22, IL-23, and TNF-α) compared to the placebo group.

Rheumatoid Arthritis

We evaluated VYN202 in two preclinical models of rheumatoid arthritis.

In a 21-day collagen-induced arthritis (CIA) model, signs and symptoms of inflammatory arthritis were induced in Lewis rats.

Each treatment group orally received placebo, GSK620 (an early generation less BD2-selective BET inhibitor) at 10 mg/kg, or VYN202 at one of three different dose strengths (1, 3, or 10 mg/kg).

Daily treatment with VYN202 10 mg/kg resulted in a 71% reduction in the overall signs and symptoms of rheumatoid arthritis at day 21 and a 79% lower paw volume (a measure of swelling) compared to mice receiving placebo.

Of the animals treated with the highest dose of VYN202, 75% presented with normal joint histopathology at the end of the study, whereas animals treated with placebo experienced marked inflammatory cell infiltrate, granulation tissue, bone erosion and cartilage ulceration.

The administration of VYN202 10 mg/kg also achieved a 98% lower expression of anti-collagen II antibody compared to placebo.

In a 21-day adjuvant-induced arthritis (AIA) model in Lewis rats, test animals were randomly assigned to 7 groups:

two vehicle groups, dexamethasone, upadacitinib, and VYN202 at one of three different dose strengths (0.1, 1, or 10 mg/kg).

All but one of the vehicle groups were induced with the adjuvant to replicate signs and symptoms of inflammation on the paws and joints of the animals.

Induced animals were then orally administered either vehicle, reference compound or VYN202 doses for 15 consecutive days.

Compared to the vehicle+adjuvant group, all strengths of VYN202 had a significant effect on inhibiting inflammation in the paws, comparable to the reference compound, upadacitinib.

The highest concentration of VYN202 resulted in an approximately 88% reduction in paw volume compared to the vehicle group.

Histopathology scores showed VYN202 had a significant effect on preventing ankle inflammation compared to the control group with VYN202 10 mg/kg having a 67% reduction compared to control and upadacitinib 10 mg/kg demonstrating a 56% reduction compared to control.

By maximizing BD2 selectivity, we believe VYN202 may alleviate these toxicities observed by other less BD2-selective BET inhibitors in development for oncology and have the potential to be a potent, oral immunomodulator option for both acute control and chronic management of immune-mediated conditions, where the damaging effects of unrestricted inflammatory signaling activities are common.

Phase 1b Trial

In February 2025, we initiated a Phase 1b trial of VYN202 in adult subjects with moderate-to-severe plaque psoriasis.

In April 2025, the FDA verbally placed a clinical hold on our Phase 1b trial following an observation of testicular toxicity in dogs from a non-clinical toxicology study of VYN202.

In June 2025, the FDA lifted the clinical hold for two doses of VYN202 for female subjects.

Further, the FDA indicated that sufficient data from a 12-week non-clinical toxicology study of VYN202 in dogs would be required in order to resume studies in male clinical subjects.

The design of this toxicology study was agreed upon with the FDA.

There were no serious adverse events observed in subjects that were enrolled in the Phase 1b trial.

Following the clinical hold, we made the decision to unblind the clinical data from the seven subjects who were enrolled in the trial (VYN202 treated:

n=6 across 0.25 mg, 0.5 mg and 1 mg doses;

placebo treated:

All subjects treated with VYN202 had an improvement in signs and symptoms of disease, while the subject who received placebo did not.

Two subjects who enrolled in the trial also co-presented with psoriatic arthritis.

The subject on VYN202 reported improvements in joint pain and showed a corresponding reduction in serum c-reactive protein levels, a biomarker associated with psoriatic arthritis and other rheumatic diseases, while the subject on placebo showed no joint pain improvement or biomarker reduction.

In October 2025, we initiated the repeat non-clinical toxicology study of VYN202 in male dogs to remedy the partial hold in male clinical subjects.

The study is expected to be completed in the second half of 2026, with a final report expected in the fourth quarter of 2026.

Manufacturing

We currently contract with third party manufacturers for all of our required raw materials, active ingredients and finished products for our preclinical studies and clinical trials for our product candidates.

We have historically contracted with third-party manufacturers for all of our required raw materials, active ingredients and finished products for our preclinical studies and clinical trials for our product candidates.

We currently have no plans to establish our own manufacturing capabilities and plan to continue to rely on third-party manufacturers for any future trials of our product candidates.

Together with contract manufacturing organizations ("CMOs"), we have developed the validation processes, methods, tests and/or controls that we believe are suitable for the manufacturing of our product candidates and for defining their properties.

Development stage quantities of any products that we develop need to be manufactured in facilities and by processes that comply with the requirements of the FDA and the regulatory agencies of other jurisdictions in which we may seek approval.

We require all of our CMOs to comply with these requirements and currently employ internal and external resources to manage our manufacturing contractors.

The relevant manufacturers of our product candidates for our current preclinical and clinical trials have advised us that they are compliant with both the FDA’s Good Laboratory Practices ("GLP") and the FDA's current Good Manufacturing Practice ("cGMP") guidances.

Together with contract manufacturing organizations (“CMOs”), we previously developed the validation processes, methods, tests and/or controls that we believed were suitable for the manufacturing of our product candidates and for defining their properties.

Development stage quantities of any products that we developed needed to be manufactured in facilities and by processes that complied with the requirements of the FDA and the regulatory agencies of other jurisdictions in which it may have sought approval.

We required all of our CMOs to comply with these requirements and employed internal and external resources to manage our manufacturing contractors.

In addition, the relevant manufacturers of our product candidates for our prior preclinical and clinical trials advised us that they were compliant with both the FDA’s Good Laboratory Practices (“GLP”) and the FDA's current Good Manufacturing Practice (“cGMP”) guidances.

Development and License Agreements

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Pursuant to the Option Agreement, Tay granted us an exclusive option to obtain certain exclusive worldwide rights to research, develop and commercialize products containing Tay’s BET inhibitor compounds for the treatment of any disease, disorder or condition in humans.

Pursuant to the Option Agreement, we agreed to use commercially reasonable efforts to develop and manufacture a product with a pan-BD BET inhibitor as its active ingredient, and Tay agreed to provide a mutually agreed data package and select a new chemical entity development candidate from its Oral BETi Compounds.

We paid a $1.0 million non-refundable cash payment to Tay upon execution of the Option Agreement.

Under the terms of the Option Agreement, our option (the "Oral Option") with respect to the Oral BETi Compounds was to expire on June 30, 2022, but in June 2022, we and Tay entered into a letter agreement to extend the option term to February 28, 2023.

In February 2023, we and Tay entered into an additional letter agreement pursuant to which the option term was further extended to April 30, 2023.

We exercised the Oral Option for VYN202 on April 28, 2023 as described below.

See "Part II—Item 7.

Management's Discussion and Analysis of Financial Condition and Results of Operations—Development and License Agreements—Agreements with Tay Therapeutics—Evaluation and Option Agreement" for a discussion regarding payments made to Tay in connection with the extension of the term for the Oral Option.

Under the terms of the Option Agreement, our option (the “Oral Option”) with respect to the Oral BETi Compounds was to expire on June 30, 2022, but in June 2022, we entered into a letter agreement with Tay to extend the option term to February 28, 2023.

In February 2023, we entered into an additional letter agreement with Tay pursuant to which the option term was further extended to April 30, 2023.

We exercised the Oral Option for VYN202 on April 28, 2023.

License for Locally Administered Pan-BD BET Inhibitor Program (Repibresib)

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jurisdictions.

In addition, with respect to any products we commercialize under the Repibresib License Agreement, we will pay tiered royalties to Tay on net sales of such licensed products by us, our affiliates, or sublicensees, of 5%, 7.5% and 10% based on tiered annual net sales of licensed products under the Repibresib License Agreement and the VYN202 License Agreement, subject to specified reductions.

In addition, with respect to any products we commercialize under the Repibresib License Agreement, we will pay tiered royalties to Tay on net sales of such licensed products by it, our affiliates, or sublicensees, of 5%, 7.5% and 10% based on tiered annual net sales of licensed products under the Repibresib License Agreement and the VYN202 License Agreement, subject to specified reductions.

We are obligated to pay royalties until the latest of (1) the tenth anniversary of the first commercial sale of the relevant licensed product, (2) the expiration of the last valid claim of the licensed patent rights covering such licensed product in such country and (3) the expiration of regulatory exclusivity for the relevant licensed product in the relevant country, on a licensed product-by-licensed product and country-by-country basis.

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Upon termination of the Head License, the Repibresib License Agreement was accordingly amended to reflect the assignment of the intellectual property to Tay upon its payment in full to Dundee.

The amendment does not change any of Tay’s or VYNE’s rights or obligations under the Repibresib License Agreement, except that any obligations owed by VYNE to Dundee with respect to repibresib are now owed to Tay.

The amendment does not change any of Tay’s or our rights or obligations under the Repibresib License Agreement, except that any obligations owed by us to Dundee with respect to repibresib are now owed to Tay.

License for Selective BET Inhibitor Program (VYN202)

On April 28, 2023, we exercised the Oral Option and entered into a license agreement (the "VYN202 License Agreement") with Tay granting us a worldwide, exclusive license that is sublicensable through multiple tiers to exploit certain of Tay’s Oral BETi Compounds in all fields.

On April 28, 2023, we exercised the Oral Option and entered into a license agreement (the “VYN202 License Agreement”) with Tay granting it a worldwide, exclusive license that is sublicensable through multiple tiers to exploit certain of Tay’s Oral BETi Compounds in all fields.

We have the sole responsibility for development, regulatory, marketing and commercialization activities to be conducted for the licensed products at our sole cost and discretion, and shall use commercially reasonable efforts to develop and, if approved, commercialize such products.

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We made a cash payment of $3.75 million to Tay in connection with entering into the VYN202 License Agreement.

Pursuant to the terms of the VYN202 License Agreement, we agreed to make cash payments to Tay of up to $43.75 million upon the

achievement of specified clinical development and regulatory approval milestones with respect to each licensed oral product in the United States for all indications, of which $1.3 million has been paid or accrued through December 31, 2024.

Pursuant to the terms of the VYN202 License Agreement, we agreed to make cash payments to Tay of up to $43.75 million upon the achievement of specified clinical development and regulatory approval milestones with respect to each licensed oral product in the United States for all indications, of which $2.3 million has been paid or accrued through December 31, 2025.

In August 2025, we paid Tay $1,000,000 in partial satisfaction of the "Phase 2 Milestone" under the VYN202 License Agreement for the initiation of the Phase 1b trial in psoriasis and amended the VYN202 License Agreement to provide that upon initiation of a new clinical trial in a target patient population involving VYN202 for oral administration with an efficacy endpoint, regardless of the trial's phase designation or regulatory classification, we shall pay Tay the remaining $4,000,000 amount under the "Phase 2 Milestone." All other terms of the VYN202 License Agreement were unchanged.

Tay is entitled to additional milestone payments upon the achievement of regulatory approvals in certain non-U.S.

jurisdictions.

In addition, with respect to any products we commercialize under the VYN202 License Agreement, we will pay tiered royalties to Tay on net sales of such licensed products by us, our affiliates, or sublicensees, of 5%, 7.5% and 10% based on tiered annual net sales of licensed products under the VYN202 License Agreement and the Repibresib License Agreement, subject to specified reductions.

In addition, with respect to any products we commercialize under the VYN202 License Agreement, we will pay tiered royalties to Tay on net sales of such licensed products by it, our affiliates, or sublicensees, of 5%, 7.5% and 10% based on tiered annual net sales of licensed products under the VYN202 License Agreement and the Repibresib License Agreement, subject to specified reductions.

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In addition, our trade secrets and other proprietary and confidential information may otherwise become known or be independently discovered by competitors.

To the extent that our employees, scientific advisors, consultants, partners, or other contractors use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.

To the extent that our employees, scientific advisors, consultants, partners, or other contractors use intellectual property owned by others in their work for it, disputes may arise as to the rights in related or resulting know-how and inventions.

Our success will also depend at least in part on not infringing the proprietary rights of third parties.

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It is uncertain whether the issuance of any third party patent would require us to alter our development strategies, alter our processes, obtain licenses or cease certain activities.

Our breach of any license agreements or failure to obtain a license to proprietary rights that we may require to develop our current and future product candidates may have a material adverse impact on us.

If third parties prepare and file patent applications in the United States that also claim technology to which we have rights, we may have to participate in derivation, interference or other proceedings in the United States Patent and Trademark Office (“USPTO”) to determine derivation or priority of invention.

We may also have to participate in court proceedings or arbitration to defend and assert our rights.

See "Item 1A.

Risk Factors—Risks Related to Our Intellectual Property."

Our BET inhibitor patent portfolio is licensed in and/or is being developed by us and comprises or is derived from several PCT applications, various national applications and certain provisional applications.

As of December 31, 2024, our patent portfolio in relation to our repibresib program includes a granted patent in the United Kingdom, Indonesia, Israel, India, Mexico, and South Africa and pending compound and composition patent applications licensed by us from Tay.

As of December 31, 2025, our patent portfolio in relation to our repibresib program includes granted patents in the United States, Europe, Eurasia, Hong Kong, Indonesia, Israel, India, Japan, Mexico, and South Africa and pending compound and composition patent applications in the United States, China, Europe, New Zealand, Australia, Brazil, Canada, South Korea, New Zealand, and Thailand, licensed from Tay.

A PCT application covering the compound, which published as WO 2020/216779, was filed nationally in more than 15 jurisdictions, including the U.S., China, Europe, Eurasia, and Japan.

Subject to being granted and payments of the appropriate maintenance fees, each patent will expire in 2040, without accounting for any potential patent term adjustment in the U.S.

A PCT application covering methods of use, which published as WO 2023/081720, was filed nationally in ten jurisdictions, including the U.S., China, Europe, Eurasia, and Japan.

Subject to being granted and payments of the appropriate maintenance fees, each patent will expire in 2042, without accounting for any potential patent term adjustment in the U.S.

In addition, a PCT application, which published as WO 2024/220589, was filed nationally in ten jurisdictions, including the U.S., China, Europe, Eurasia, and Japan.

Subject to being granted and payments of the appropriate maintenance fees, each patent will expire in 2042, without accounting for any potential patent term adjustment in the U.S.

In addition, a PCT application, which published as WO 2024/220589, and a provisional application directed to various uses of repibresib have been filed.

Subject to the PCT application being filed nationally, filing a non-provisional application, and these patent applications being granted and payments of the appropriate maintenance fees, each patent will expire in 2042 and 2044, respectively, without accounting for any potential patent term adjustment in the U.S.

As of December 31, 2024, our patent portfolio in relation to our VYN202 program includes a granted patent in the United Kingdom and pending compound and composition patent applications licensed by us from Tay.

Subject to being granted and payments of the appropriate maintenance fees, each patent will expire in 2040, without accounting for any potential patent term adjustment in the United States.

In addition, two provisional applications directed to various uses of repibresib are pending.

Subject to the provisional application converting to a non-provisional application and these patent applications being granted and payments of the appropriate maintenance fee, each patent will expire in 2046, without accounting for any potential patent term adjustment in the United States.

As of December 31, 2025, VYNE’s patent portfolio in relation to VYNE’s VYN202 program includes a granted patent in the United Kingdom and pending compound and composition patent applications in Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, Indonesia, Israel, India, Japan, South Korea, Mexico, New Zealand, Thailand, United States, and South Africa, licensed from Tay.

A PCT application covering the compound, which published as WO 2023/275542, was filed nationally in more than 15 jurisdictions, including the U.S., China, Europe, Eurasia and Japan.

Subject to being granted and payments of the appropriate maintenance fees, each patent will expire

in 2042, without accounting for any potential patent term adjustment in the United States.

Two additional compound and composition PCT applications were also filed in relation to VYN202 and our oral BD2-selective BET inhibitor program exclusively licensed by us from Tay.

Subject to these PCT applications being filed nationally, one of which published as WO 2024/018423, and the patent applications being granted and payments of the appropriate maintenance fees, the patents will expire in 2043, without accounting for any potential patent term adjustment in the United States.

In addition, a provisional application directed to VYN202 method of use has been filed.

Subject to filing a non-provisional and this patent application being granted and payments of the appropriate maintenance fees, this patent would expire in 2045, without accounting for any potential patent term adjustment in the United States.

Subject to being granted and payments of the appropriate maintenance fees, each patent will expire in 2042, without accounting for any potential patent term adjustment in the United States.

Two additional compound and composition PCT applications were also filed in relation to VYN202 and our oral BD2-selective BET inhibitor program exclusively licensed from Tay.

A PCT application covering compounds and compositions related to VYN202, which published as WO 2024/138201, is pending nationally in the United States, Europe, Australia, Brazil, Canada, China, Eurasia, United Kingdom, Indonesia, Israel, India, Japan, South Korea, Mexico, New Zealand, Thailand, and South Africa.

Subject to being granted and payment of the appropriate maintenance fees, each patent will expire in 2043, without accounting for any potential patent term adjustment in the United States An additional PCT covering compounds and compositions related to VYN202, which published as WO 2024/018423, is pending nationally in the United States and Europe.

Subject to being granted and payment of the appropriate maintenance fees, each patent will expire in 2043, without accounting for any potential patent term adjustment in the United States.

One additional PCT application directed to various uses of VYN202 is pending in relation to VYN202.

Subject to this PCT application being filed nationally, and the patent applications being granted and payments of the appropriate maintenance fees, the patents will expire in 2045, without accounting for any potential patent term adjustment in the United States In addition, six provisional applications directed to VYN202 method of use and combination therapies are pending.

Subject to filing a non-provisional and the patent applications being granted and payments of the appropriate maintenance fees, this patent would expire in 2046, without accounting for any potential patent term adjustment in the United States.

Patents extend for varying periods according to the date of patent filing or grant and the legal term of patents in various countries where patent protection is obtained.

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Any product candidate that we successfully develop and commercialize will compete with existing treatments, including those that may have achieved broad market acceptance, and any new treatment that may become available in the future.

Many of the companies against which we are competing, or against which we may compete in the future, have significantly greater financial resources and expertise in research and development, manufacturing, and preclinical and clinical development than we do.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and subject registration for clinical trials, as well as in acquiring technologies complementary to, or that may be necessary for, our development programs.

For vitiligo, our primary competitors include topical therapies such as generic and branded versions of calcineurin inhibitors, including ELIDEL, marketed by Bausch Health;

OPZELURA, a topical JAK inhibitor marketed by Incyte Corporation;

branded and generic versions of high potency steroids, including CLOBEX, marketed by Galderma Laboratories, LP;

and other treatments including various lasers and ultraviolet light-based therapies.

In addition, there are several prescription product candidates under development that could potentially be used to treat vitiligo and compete with repibresib gel, if approved, including but not limited to oral JAK inhibitors being developed by Incyte, Pfizer and AbbVie.

We intend to develop VYN202 for the treatment of various immune-mediated conditions.

Our initial proof-of-concept indication is moderate-to-severe plaque psoriasis which is a competitive market.

We are currently developing VYN202 for the treatment of various immune-mediated conditions, which include indications in highly competitive markets.

Many companies, including large pharmaceutical companies such as AbbVie, Amgen, Bristol Myers Squibb, Johnson & Johnson, UCB, LEO Pharma, Janssen Pharmaceuticals, Roche, Eli Lilly, Pfizer and others, have approved drugs (and are developing) small molecule and biologics in these therapeutic classes.

For example, our initial proof-of-concept indication was moderate-to-severe plaque psoriasis which is a competitive market.

The psoriasis market includes several approved anti-IL-17 antibody therapies, including COSENTYX, marketed by Novartis;

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Furthermore, the oral PDE4 inhibitor, OTEZLA, marketed by Amgen, and oral TYK2 inhibitor, SOTYKTU, marketed by Bristol Myers Squibb, are approved for the treatment of psoriasis.

In addition, we are aware of other oral therapeutic candidates including other TYK2 inhibitors, oral IL-17 inhibitors, and oral IL-23 inhibitors being developed by Takeda Pharmaceutical Company, Ventyx Biosciences, Eli Lilly, LEO Pharma, Janssen Pharmaceuticals, among others.

We anticipate our second indication, subject to adequate levels of funding, will be rheumatoid arthritis which is also a competitive market.

Medications for the treatment of rheumatoid arthritis include corticosteroids and disease-modifying anti-rheumatic drugs ("DMARDs").

DMARDs include (i) methotrexate, sulfasalazine, leflunomide and hydroxychloroquine, (ii) biologic DMARDs, and (iii) targeted synthetic DMARDs such as JAK inhibitors.

These drugs are produced and sold, or are approved for marketing, by large pharmaceutical companies, including AbbVie, Amgen, Bristol Myers Squibb, Johnson & Johnson, UCB, Roche, Eli Lilly, and Pfizer.

In addition, several other

companies are developing drugs for the treatment of rheumatoid arthritis that, if approved, could compete with VYN202 if the indication is pursued and approved.

Similarly, any potential alternative indications for which we develop VYN202 may also be in highly competitive markets.

The commercial opportunity for our product candidates, if approved, could be reduced or eliminated if our competitors develop and commercialize drugs that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any drug we may develop.

Our competitors also may obtain FDA or other regulatory approval for their product candidates more rapidly than us, which could result in our competitors establishing a strong market position before our product candidates are able to enter the market.

Our competitors also may obtain FDA or other regulatory approval for their product candidates more rapidly than it, which could result in our competitors establishing a strong market position before our product candidates are able to enter the market.

Government Regulation

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Before approving an NDA, the FDA may inspect the facilities at which the product is manufactured or facilities that are significantly involved in the product development and distribution process, and will not approve the product unless cGMP compliance is satisfactory at such facilities.

The FDA may deny approval of a NDA if applicable statutory or regulatory criteria are not satisfied, or it may require additional testing or information, which can delay the approval process.

The FDA may deny approval of an NDA if applicable statutory or regulatory criteria are not satisfied, or it may require additional testing or information, which can delay the approval process.

FDA approval of any application may include many delays or may never be granted.

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Both fast track and breakthrough therapy products are also eligible for accelerated approval and/or priority review, if relevant criteria are met.

likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Under the FDA’s accelerated approval regulations, the FDA may approve a drug for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

In clinical trials, a surrogate endpoint is a measurement of laboratory or clinical signs of a disease or condition that substitutes for a direct measurement of how a patient feels, functions, or survives.

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Moreover, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved, or that other payors will similarly provide similar coverage for the product.

Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on its investment in product development.

Further, there has been increasing legislative and enforcement interest in the United States with respect to drug pricing practices, including several recent U.S.

Congressional inquiries and federal and state legislation designed to, among other things, increase drug pricing transparency, expedite generic competition, review relationships between pricing and manufacturer patient assistance programs, and reform government program drug reimbursement methodologies.

Department of Health and Human Services (“HHS”) imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis.

In addition, HHS has been empowered to negotiate the price to negotiate the price of certain single-source drugs that have been on the market for at least 7 years covered under Medicare as part of the Medicare Drug Price Negotiation Program.

Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program.

Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

CMS administers the Medicaid drug rebate program, in which pharmaceutical manufacturers pay quarterly rebates to each state Medicaid agency.

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There have been executive, judicial, Congressional, and political challenges and amendments to certain aspects of the ACA.

For example on August 16, 2022, the Inflation Reduction Act of 2022 ("IRA") was signed 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.

For example, on July 4, 2025, the One Big Beautiful Bill Act ("OBBBA"), was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

It is possible that there will be additional health reform measures.

It is unclear how any such challenges, if any, and other efforts to modify, repeal and replace the ACA will impact the ACA.

Further, there has been increasing legislative and enforcement interest in the United States with respect to drug pricing practices, including several recent U.S.

For example, 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 that have been on the market for at least 7 years covered under Medicare (the “Medicare Drug Price Negotiation Program”), and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions take effect progressively starting in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon prices of the first ten drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges.

On January 17, 2025, HHS selected fifteen additional drugs covered under Part D for price negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

Further, on December 7, 2023, an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act was announced, allowing an agency to grant a compulsory license on a privately owned patent to third parties, if the invention was developed with federal funding and the agency finds that certain statutory criteria apply.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one

factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

The current administration is pursuing policies to reduce regulations and expenditures across government agencies including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

For example, the current administration has announced agreements with pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform, U.S.

patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues.

Other recent actions, for example, include (1) directing agencies to reduce agency workforce and cut programs;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the Make America Healthy Again (MAHA) Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

These actions and policies may significantly reduce U.S.

drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

In June 2024, the U.S.

Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.

At the state level, legislatures are 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.

For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program (“SIP”) proposal to import certain drugs from Canada for specific state healthcare programs.

It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada.

Other states have also submitted SIP proposals that are pending review by the FDA.

Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

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and state laws related to insurance fraud in the case of claims involving private insurers.

If our operations are found to be in violation of any of the healthcare laws or regulations described above or any other healthcare regulations that apply to us, we may be subject to significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, imprisonment, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or consent decree, reputational harm, diminished profits and future earnings, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and pursue our strategy.

If our operations are found to be in violation of any of the healthcare laws or regulations described above or any other healthcare regulations that apply to it, we may be subject to significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, imprisonment, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or consent decree, reputational harm, diminished profits and future earnings, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and pursue our strategy.

Environmental, Health and Safety Matters

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These laws, regulations and permits could potentially require the expenditure by us of significant amounts for compliance or remediation.

If we fail to comply with such laws, regulations or permits, we may be subject to fines and other civil, administrative or criminal sanctions, including the revocation of permits and licenses necessary to continue our business activities.

If we fail to comply with such laws, regulations or permits, it may be subject to fines and other civil, administrative or criminal sanctions, including the revocation of permits and licenses necessary to continue our business activities.

In addition, we may be required to pay damages or civil judgments in respect of third party claims, including those relating to personal injury (including exposure to hazardous substances we use, store, handle, transport, manufacture or dispose of), property damage or contribution claims.

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From time to time, we also retain independent contractors and consultants to support our organization.

We believe our internal R&D capabilities coupled with our third-party R&D consultants are sufficient to execute our clinical development strategy in a cost-effective manner.

We believe that our internal R&D capabilities coupled with our third-party R&D consultants are sufficient to execute our clinical development strategy in a cost-effective manner.

None of our employees are represented by a labor union, and we consider our employee relations to be good.

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See the risk factor captioned “We are eligible to report as a ‘smaller reporting company,’ and as a result of the reduced reporting requirements applicable to such companies, our securities may be less attractive to investors” for more information.

Our principal executive offices are located at 685 Route 202/206 N., Suite 301, Bridgewater, NJ 08807.

Our principal executive offices were previously located in Bridgewater, NJ.

Effective November 1, 2025, we have been operating on a fully remote model.

Our website is www.vynetherapeutics.com.

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Therefore, investors should monitor our website in addition to following its press releases, filings with the SEC, public conference calls, and webcasts.

The contents of our website are not intended to be incorporated by reference into this Annual Report on Form 10-K or in any other report or document we file with the SEC, and any references to our websites are intended to be inactive textual references only.

The contents of our website are not intended to be incorporated by reference into this Annual Report or in any other report or document we file with the SEC, and any references to our websites are intended to be inactive textual references only.

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