Core Points - VYNE Therapeutics Inc. announced a clinical hold on its Phase 1b study of VYN202 for moderate-to-severe plaque psoriasis due to observed testicular toxicity in dogs from a non-clinical toxicology study [1][2] - The company has suspended all screening, enrollment, and patient dosing in the Phase 1b trial and aims to resolve the clinical hold with the FDA as soon as possible [2] - The clinical hold does not affect VYNE's ongoing Phase 2b trial of repibresib gel for nonsegmental vitiligo, with top-line results expected mid-year [3] - The CEO of VYNE expressed disappointment over the clinical hold but emphasized the priority of patient safety and the intention to work closely with the FDA [4] - VYNE is focused on developing differentiated therapies for chronic inflammatory and immune-mediated conditions, utilizing its proprietary BET inhibitors [4]

Company Overview - VYNE Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on developing differentiated therapies for chronic inflammatory and immune-mediated conditions with high unmet need [3]. Conference Participation - VYNE's management will participate in the H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference on March 27, 2025 [1]. - The fireside chat is scheduled for 11:00 am ET on the same day [2]. - A webcast replay will be available on VYNE's website for 90 days following the event [2]. Product Development - VYNE's proprietary BET inhibitors, part of its InhiBET™ platform, aim to address limitations of earlier generation BET inhibitors by utilizing alternative administration routes and enhanced selectivity [3].

Company Overview - VYNE Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on developing differentiated therapies for chronic inflammatory and immune-mediated conditions with high unmet need [3]. Conference Participation - VYNE's management will participate in the H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference on March 27, 2025 [1]. - A fireside chat is scheduled for March 27, 2025, at 11:00 am ET, with a webcast replay available on the VYNE website for 90 days following the event [2]. Product Development - VYNE's proprietary BET inhibitors, part of its InhiBET™ platform, aim to overcome limitations of early generation BET inhibitors by utilizing alternative routes of administration and enhanced selectivity [3].

Licensing and Agreements - The company exercised the Oral Option for VYN202 on April 28, 2023, extending the option term multiple times since June 2022[61]. - A cash payment of $3.75 million was made to Tay in connection with the VYN202 License Agreement, with potential milestone payments of up to $43.75 million based on clinical development and regulatory approvals[66][67]. - The Repibresib License Agreement includes cash payments of up to $15.75 million upon achieving specified milestones, with $1.8 million paid or accrued through December 31, 2024[63]. - Tiered royalties of 5%, 7.5%, and 10% on net sales of licensed products are to be paid to Tay, with obligations lasting until the tenth anniversary of the first commercial sale or the expiration of patent rights[63][67]. - The Company executed a 1-for-18 reverse stock split on February 10, 2023, affecting the number of outstanding shares[450]. - The Company entered into an Evaluation and Option Agreement with Tay Therapeutics, paying $1.0 million, with 50% allocated for the development of Oral BETi Compounds[506]. - The Option Term for the Oral BETi Compounds was extended multiple times, with payments totaling $1.4 million made to Tay for extensions and further development[507]. - The Company exercised its option for the repibresib program, resulting in a License Agreement with an upfront payment of $0.5 million and potential milestone payments of up to $15.75 million[508][509]. - The Company entered into a VYN202 License Agreement, making a cash payment of $3.75 million and agreeing to milestone payments of up to $43.75 million[512][513]. - The MST Franchise was sold for an upfront payment of $20.0 million and an additional deferred payment of $5.0 million, with potential sales milestone payments of up to $450.0 million[514][515]. Financial Performance - Total revenues for 2024 increased to $501,000 from $424,000 in 2023, representing a growth of 18.2%[433]. - Research and development expenses surged to $30,946,000 in 2024, up from $16,307,000 in 2023, marking an increase of 89.9%[433]. - The net loss for 2024 was $39,834,000, compared to a net loss of $28,452,000 in 2023, reflecting a deterioration of 40.1%[433]. - Total current assets decreased to $64,437,000 in 2024 from $95,963,000 in 2023, a decline of 32.6%[429]. - Total liabilities increased to $14,819,000 in 2024, up from $8,950,000 in 2023, indicating a rise of 65.5%[429]. - Cash and cash equivalents at the end of 2024 were $19,926,000, down from $30,620,000 in 2023, a decrease of 34.5%[439]. - The weighted average shares outstanding increased significantly to 42,589,000 in 2024 from 10,273,000 in 2023, an increase of 314.5%[433]. - The company reported a comprehensive loss of $39,840,000 in 2024, compared to a comprehensive loss of $28,426,000 in 2023, an increase of 40.5%[433]. - Additional paid-in capital rose to $783,235,000 in 2024 from $780,044,000 in 2023, a slight increase of 0.3%[430]. - Total shareholders' equity decreased to $52,086,000 in 2024 from $88,735,000 in 2023, a decline of 41.1%[430]. - The Company reported a net loss of $39.8 million for the year ended December 31, 2024, and used $34.0 million of cash in operations[453]. - As of December 31, 2024, the Company had cash, cash equivalents, and marketable securities totaling $61.5 million, with an accumulated deficit of $731.2 million[453]. - The Company completed a private placement on November 1, 2023, raising gross proceeds of $88.2 million, resulting in net proceeds of $82.7 million after deducting issuance costs[452]. - The Company has no outstanding debt as of December 31, 2024[453]. - Royalty revenues for the year ended December 31, 2024, were $0.5 million, an increase from $0.4 million in 2023, reflecting a 25% growth[476]. - The company's net product revenues were generated through AMZEEQ and ZILXI, but no longer generate revenue from these products following the sale of the MST Franchise on January 12, 2022[480]. - The revenue reserve liability was $2.1 million as of December 31, 2024, down from $2.3 million in 2023, indicating a reduction of approximately 8.7%[481]. - The company recorded employee retention tax credits totaling $1.3 million, received in the first quarter of 2023, reflecting support during the COVID-19 pandemic[497]. - As of December 31, 2024, all outstanding warrants were classified as equity-classified, indicating no liability-classified warrants on the balance sheet[499]. - The company has provided a full valuation allowance for deferred tax assets due to ongoing losses, indicating a cautious approach to tax asset realization[490]. Research and Development - The lead program, repibresib gel (VYN201), is currently in a Phase 2b trial for the treatment of NSV[446]. - The second program, VYN202, has completed a Phase 1a trial and initiated a Phase 1b trial in February 2025 for moderate-to-severe plaque psoriasis[447]. - The company believes its internal R&D capabilities, along with third-party R&D consultants, are sufficient to execute its clinical development strategy in a cost-effective manner[130]. - Research and development expenses are expensed as incurred, reflecting the company's commitment to ongoing innovation and development[485]. Competition and Market Environment - The company faces intense competition in drug development from larger pharmaceutical companies and other organizations with greater resources[74][75]. - The initial proof-of-concept indication for VYN202 is moderate-to-severe plaque psoriasis, a competitive market with several approved therapies[77]. - The company anticipates pursuing rheumatoid arthritis as a second indication for VYN202, which also has significant competition from established medications[78]. - The company faces significant competition, which could impact the commercial opportunity for its product candidates if competitors develop safer, more effective, or less expensive alternatives[79]. Regulatory Environment - The company is subject to extensive government regulation, which significantly affects its research and development activities[80]. - The FDA requires a New Drug Application (NDA) for marketing new drug products, which involves substantial time and financial resources[81]. - The NDA submission process includes multiple phases, such as laboratory tests, animal studies, and human clinical trials, all of which must comply with FDA regulations[82]. - Clinical trials are conducted in three phases, with Phase 1 focusing on safety, Phase 2 on short-term effects, and Phase 3 on efficacy and safety for broader populations[87]. - The FDA has performance goals for reviewing NDAs, with standard reviews typically taking 10-12 months and priority reviews taking 6-8 months[87]. - The FDA may impose post-approval requirements, including additional studies or restrictions on product distribution, which can affect market potential[89]. - The company may utilize FDA expedited review programs, such as Fast Track and Breakthrough Therapy designations, to accelerate the development and review process for serious conditions[91]. - Post-approval, the company must comply with ongoing FDA regulations, including record-keeping and reporting adverse experiences, to avoid penalties[98]. - Non-compliance with FDA regulations, including off-label promotion, can lead to significant civil fines and penalties, potentially up to $1.15 million per year[99]. - The FDA's cGMP regulations require manufacturers to maintain quality control and assurance, along with comprehensive records and documentation[100]. - Drug manufacturers must register their establishments and list products with the FDA, subject to periodic inspections for compliance[100]. - Pediatric exclusivity may grant an additional 6 months of marketing protection if pediatric data is submitted upon FDA request[105]. - Patent term extensions can be granted for up to five years under the Hatch-Waxman Act, compensating for marketing time lost during FDA review[106]. - In the EEA, new chemical entities receive eight years of data exclusivity and an additional two years of market exclusivity upon receiving a Marketing Authorization[110]. - The FDA may require post-marketing testing or REMS to monitor the effects of approved products, potentially restricting distribution[102]. Compliance and Legal Risks - The company is subject to extensive environmental, health, and safety laws and regulations, which could require significant expenditures for compliance or remediation[125]. - Non-compliance with healthcare laws and regulations could result in significant penalties, including exclusion from government healthcare programs and reputational harm[124]. - The operations of subcontractors and suppliers are also subject to various laws and regulations, which could adversely affect the company's business and reputation[128]. - The company may be required to pay damages or civil judgments in respect of third-party claims related to environmental, health, and safety laws[126]. Assets and Liabilities - As of December 31, 2024, the Company reported total assets of $61.5 million, including cash and cash equivalents of $19.9 million and marketable securities of $41.6 million[520]. - The Company’s marketable securities decreased from $62.6 million in 2023 to $41.6 million in 2024, primarily due to interest rate changes[523]. - The Company had no property and equipment as of December 31, 2023, but reported $113,000 in net property and equipment as of December 31, 2024[524]. - Depreciation expense for the year ended December 31, 2024, totaled $4 thousand, compared to $0 for 2023[525]. - Total accrued expenses increased to $9,272 thousand in 2024 from $4,119 thousand in 2023, with significant increases in research and development accruals from $990 thousand to $6,622 thousand[526]. - Operating lease expense rose to $126 thousand in 2024 from $32 thousand in 2023, contributing to a total lease expense of $136 thousand[530]. - The Company recorded a right of use asset of $200 thousand and a liability of $300 thousand at the commencement of the Master Lease on October 1, 2023[529]. - Operating lease right-of-use assets decreased to $93 thousand as of December 31, 2024, from $207 thousand in 2023[532]. - The weighted average remaining lease term decreased from 1.75 years in 2023 to 0.75 years in 2024[532]. - The Company made contributions of $100 thousand to its 401(k) Plans for both 2024 and 2023[533]. - As of December 31, 2024, there were no shares of preferred stock issued and outstanding, despite authorization for 20,000,000 shares[535]. - The Company issued 3,000 shares of Series A Convertible Preferred Stock for a total subscription amount of $300,000, resulting in net proceeds of $211,000 after issuance costs[537]. - The Proposal for a reverse stock split of outstanding common stock was approved during a stockholder meeting on January 12, 2023[539].

Financial Position - As of December 31, 2024, VYNE had a cash position of $61.5 million, sufficient to fund operations into the second half of 2026[8]. - Total assets decreased to $66.9 million in 2024 from $97.7 million in 2023[19]. - Total liabilities increased to $14.8 million in 2024 from $8.9 million in 2023[19]. - The company had 14,830,013 common shares issued and outstanding as of December 31, 2024[9]. Revenue Performance - Revenues for the year ended December 31, 2024, totaled $0.5 million, a 25% increase from $0.4 million in 2023, primarily from royalty revenue[9]. - Total revenues for the year ended December 31, 2024, reached $501 million, compared to $424 million in 2023, marking a 18.1% growth[21]. - Royalty revenues for Q4 2024 were $84 million, up from $76 million in Q4 2023, representing a 10.5% increase[21]. Expenses - Research and development expenses increased to $30.9 million in 2024, up 89% from $16.3 million in 2023, driven by costs associated with repibresib and VYN202[9]. - General and administrative expenses slightly decreased to approximately $13.2 million in 2024 from $13.4 million in 2023[10]. - Total operating expenses for the year increased to $44.138 million from $29.682 million, a rise of 48.8%[21]. - Research and development expenses surged to $9.684 million in Q4 2024, compared to $3.023 million in Q4 2023, reflecting a 220.5% increase[21]. Net Loss - The net loss for the year ended December 31, 2024, was $39.8 million, with a net loss per share of $0.93, compared to a net loss of $28.5 million and a net loss per share of $2.78 in 2023[11]. - Net loss for the year ended December 31, 2024, was $39.834 million, up from $28.452 million in 2023, representing a 40.1% increase[21]. - The operating loss for Q4 2024 was $12.770 million, compared to a loss of $6.832 million in Q4 2023, indicating an increase in losses of 87.5%[21]. - Loss per share from continuing operations for Q4 2024 was $0.28, compared to $0.20 in Q4 2023, reflecting a 40% increase in loss per share[21]. Future Expectations - VYNE expects topline results from the Phase 2b trial of repibresib gel in nonsegmental vitiligo in mid-2025[5]. - The Phase 1b trial of VYN202 for moderate-to-severe plaque psoriasis has been initiated, with topline results anticipated by the end of 2025[5].

Core Viewpoint - VYNE Therapeutics Inc. reported financial results for the fourth quarter and year ended December 31, 2024, highlighting significant progress in its clinical pipeline and upcoming data readouts for its product candidates in 2025 [1][2]. Financial Results - As of December 31, 2024, VYNE had a cash position of $61.5 million, which is expected to fund operations into the second half of 2026 [8]. - Revenues for the year ended December 31, 2024, totaled $0.5 million, an increase from $0.4 million in 2023, primarily from royalty revenue [9]. - Research and development expenses rose to $30.9 million in 2024 from $16.3 million in 2023, driven by increased costs associated with clinical trials for repibresib and VYN202 [10]. - General and administrative expenses slightly decreased to approximately $13.2 million in 2024 from $13.4 million in 2023 [11]. - The net loss for the year ended December 31, 2024, was $39.8 million, or $0.93 per share, compared to a net loss of $28.5 million, or $2.78 per share, in 2023 [12]. Pipeline Updates - VYNE is advancing its clinical pipeline with two key data readouts expected in 2025: topline results from the Phase 2b trial of repibresib gel in nonsegmental vitiligo anticipated in mid-2025, and topline results from the Phase 1b trial of VYN202 in moderate-to-severe plaque psoriasis expected by the end of 2025 [2][6]. - The Phase 2b trial of repibresib gel involves a randomized, double-blind, vehicle-controlled design with three dose cohorts (1%, 2%, or 3% concentrations) and approximately 180 subjects [7]. - The Phase 1b trial of VYN202 has been initiated, evaluating three dosing cohorts (0.25 mg, 0.5 mg, 1 mg) in subjects with moderate-to-severe plaque psoriasis [7]. Upcoming Events - VYNE will participate in the Leerink Partners Global Healthcare Conference in Miami from March 10-12, 2025, and the H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference on March 27, 2025 [5].

Company Overview - VYNE Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on developing differentiated therapies for chronic inflammatory and immune-mediated conditions with high unmet need [3]. Upcoming Investor Conferences - VYNE's management will participate in two investor conferences in March 2025: - TD Cowen 45th Annual Health Care Conference in Boston, MA on March 4, 2025, featuring a fireside chat and one-on-one meetings [1]. - Leerink Partners Global Healthcare Conference in Miami, FL on March 11, 2025, consisting of one-on-one meetings [2]. Product Development - VYNE's proprietary BET inhibitors, part of its InhiBET™ platform, aim to address limitations of early generation BET inhibitors by utilizing alternative routes of administration and enhanced selectivity [3].

Core Insights - VYNE Therapeutics Inc. has initiated a Phase 1b trial for VYN202, an oral small molecule BET inhibitor, targeting moderate-to-severe plaque psoriasis, marking a significant advancement in its clinical development [1][2][3] - The trial aims to evaluate the safety, tolerability, and pharmacokinetics of VYN202 over a 12-week period, with top-line data expected by the end of 2025 [1][3][6] Company Overview - VYNE Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for chronic inflammatory and immune-mediated conditions with high unmet needs [9] - The company’s proprietary BET inhibitors, including VYN202, are designed to overcome limitations of earlier generation BET inhibitors through enhanced selectivity and alternative administration routes [9] Product Details - VYN202 is characterized as a highly selective oral BET inhibitor with potential advantages in treating immune-mediated diseases due to its class-leading selectivity for BD2 over BD1 [5][6] - The Phase 1b trial will include three dosing cohorts (0.25 mg, 0.5 mg, 1 mg) and will assess exploratory efficacy measures such as PASI scores and quality of life [3][4] Disease Context - Plaque psoriasis is a chronic immune-mediated disease affecting over 8 million Americans and more than 125 million people globally, characterized by inflamed, scaly plaques [4] - The disease shares common inflammatory pathways with other chronic conditions, suggesting potential broader applications for VYN202 in treating various immune-mediated diseases [4][2]

Core Insights - VYNE Therapeutics Inc. has completed enrollment in its Phase 2b trial for VYN201 gel, aimed at treating nonsegmental vitiligo, with top-line data expected in mid-2025 [1][2][8] Company Overview - VYNE Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on developing differentiated therapies for chronic inflammatory and immune-mediated conditions with high unmet needs [9] - The company utilizes a proprietary InhiBET™ platform, which includes unique BET inhibitors designed to enhance selectivity and overcome limitations of earlier generation BET inhibitors [9] Product Development - The Phase 2b trial for VYN201 gel (now named repibresib) is a randomized, double-blind, vehicle-controlled study assessing the efficacy, safety, and pharmacokinetics of the gel in three dose cohorts (1%, 2%, and 3%) over a 24-week period [3][4] - The primary efficacy endpoint is the proportion of subjects achieving at least a 50% improvement in the Facial Vitiligo Area Scoring Index (F-VASI50) at week 24 compared to the vehicle group [4] Disease Context - Vitiligo is a chronic autoimmune disorder characterized by the loss of melanocytes, affecting approximately 0.5-2.0% of the global population, with nonsegmental vitiligo being the most common type [5] - Currently, there is only one FDA-approved treatment for vitiligo, highlighting the significant unmet medical need in this area [5] Mechanism of Action - Repibresib is a pan-bromodomain BET inhibitor designed for local administration, targeting multiple inflammatory cell signaling pathways while minimizing systemic exposure [6] - BET proteins play a crucial role in regulating gene transcription and immune cell activation, making BET inhibitors promising for treating various immuno-inflammatory and fibrotic diseases [7]

Core Insights - VYN202 shows promising results as a novel, once-daily oral treatment for various immune-mediated disorders, demonstrating a favorable safety and tolerability profile [1][3] - The Phase 1a trial results indicate robust pharmacodynamic activity, including significant inhibition of inflammatory biomarkers [1][2] Safety and Tolerability - VYN202 exhibited no drug-related adverse events historically associated with earlier generation BET inhibitors, such as thrombocytopenia and gastrointestinal toxicity [2][4] - All treatment-emergent adverse events (TEAEs) were mild or moderate, with no serious adverse events reported [2][3] Pharmacokinetics (PK) - VYN202 supports a once-daily dosing regimen, achieving steady-state after 7 doses [2][4] - Blood levels of VYN202 remained within key inhibitory thresholds for at least 24 hours across all doses [2][4] - No drug-drug interactions were observed when co-administered with methotrexate [2][4] Pharmacodynamics - VYN202 induced a dose-dependent increase in the target engagement biomarker HEXIM-11, with maximal effects at doses of 0.5mg to 1.0mg [2][5] - The drug inhibited multiple inflammatory biomarkers related to Th17 and Th1/myeloid dysregulated activity, consistent with preclinical models [2][6] Development and Future Plans - The positive results from the Phase 1a trial support further development of VYN202 as a treatment option for immune-mediated diseases [3][9] - The company plans to finalize clinical trial plans for VYN202 based on these encouraging results [3][9] About VYN202 - VYN202 is an innovative oral small molecule BET inhibitor designed for enhanced selectivity and potency, particularly for BD2 versus BD1 [6][9] - It aims to provide a differentiated, non-biologic treatment option for chronic inflammatory conditions [6][9]