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Repibresib gel (VYN201) Phase 2b vitiligo top-line results expected in mid-2025 VYN202 Phase 1b psoriasis trial initiated with results anticipated by year-end 2025 Expected cash runway into 2H 2026 BRIDGEWATER, N.J., March 06, 2025 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need, today announced financial results as of and for the fourth quarter and year ended December 31, 2024, and provided a business update. “Based on our significant progress in 2024, we are now positioned to announce two key data readouts for repibresib gel and VYN202 in 2025,” said David Domzalski, President and Chief Executive Officer of VYNE. “We are off to a strong start in 2025. In January, we announced the completion of enrollment in the Phase 2b trial of our locally administered pan-BD BET inhibitor, repibresib, in nonsegmental vitiligo, and we expect to report topline results in mid-2025. We also recently initiated the Phase 1b trial of our oral BD2-selective BET inhibitor, VYN202, in subjects with moderate-to-severe plaque psoriasis, and we anticipate reporting topline results from this trial by the end of this year.” Recent Pipeline Updates Repibresib gel (VYN201), a locally-administered small molecule pan-BD BET inhibitor (Phase 2b, nonsegmental vitiligo): Top-line results from the Phase 2b trial are expected in mid-2025. The fully enrolled, Phase 2b trial (NCT06493578) is a randomized, double-blind, vehicle-controlled trial evaluating the efficacy, safety and pharmacokinetics of once-daily repibresib gel in three dose cohorts (1%, 2% or 3% concentrations) compared to vehicle for 24 weeks in subjects with active or stable nonsegmental vitiligo. Subjects have been randomized equally (1:1:1:1 ratio) across the active drug cohorts or vehicle (approximately 45 subjects in each arm). Top-line results from the 24-week double-blind, vehicle-controlled portion of the trial are expected mid-year. Following the 24-week treatment period, subjects who have been randomized in the three active dose cohorts will continue treatment with their respective dose concentrations for an additional 28-week active treatment extension. Subjects who have been randomized in the vehicle group during the initial 24-week treatment period will be equally re-randomized into one of the three active dose cohorts for an additional 28 weeks. VYN202, an oral small molecule BD2-selective inhibitor: Top-line results from the Phase 1b trial are expected by year-end 2025. In February 2025, the Company announced the initiation of patient enrollment in the Phase 1b trial which is a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability and pharmacokinetics of once-daily VYN202 in three dosing cohorts (0.25 mg, 0.5 mg, 1 mg doses) compared to placebo, for 12 weeks in subjects with moderate-to-severe plaque psoriasis. Exploratory efficacy of VYN202 will also be evaluated, including measures of psoriasis area and severity index, Static Physician Global Assessment, scalp disease, quality of life, and biomarker analyses. Subjects will be randomized equally (1:1:1:1, approximately 20 subjects per arm) across the active drug cohorts or placebo. Following the 12-week treatment period, all subjects will be followed for a 4-week safety period. Upcoming Conference Participation Investor Conferences. VYNE will be participating in the upcoming Leerink Partners Global Healthcare Conference, taking place in Miami from March 10-12, 2025, as well as the H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference being held on March 27, 2025. Financial Results as of and for the Year Ended December 31, 2024 Cash position. As of December 31, 2024, VYNE had $61.5 million of cash, cash equivalents and marketable securities. Based on current operating assumptions, VYNE believes its cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund its operations into the second half of 2026. Share count. As of December 31, 2024, VYNE had 14,830,013 common shares issued and outstanding, and outstanding pre-funded warrants to purchase 27,842,740 shares of common stock at an exercise price of $0.0001 per share. Revenues. Revenues totaled $0.5 million and $0.4 million for the years ended December 31, 2024 and 2023, respectively, consisting of royalty revenue from the Company's royalty agreement with LEO Pharma A/S, to whom VYNE previously licensed the rights to Finacea® foam. Research and development expenses. VYNE’s research and development expenses for the years ended December 31, 2024 and 2023 were $30.9 million and $16.3 million, respectively. The increase was primarily due to an increase of $11.7 million in expenses for repibresib, an increase of $2.5 million in expenses for VYN202 and an increase of $0.8 million of employee-related expenses following the hiring of additional research and development personnel. The $11.7 million increase in expenses for repibresib primarily relates to preparatory activity and clinical trial costs incurred for VYNE's ongoing Phase 2b trial of repibresib in subjects with nonsegmental vitiligo. The $2.5 million increase in expenses for VYN202 is primarily associated with costs incurred for our Phase 1a SAD/MAD trial which was completed in the fourth quarter of 2024. Both trials were initiated in June 2024. These increases were partially offset by lower consulting expenses of $0.4 million. General and administrative expenses. VYNE’s general and administrative expenses for the years ended December 31, 2024 and 2023 were approximately $13.2 million and $13.4 million, respectively. The decrease was primarily driven by a reduction in employee related expenses of $0.9 million, partially offset by increased consulting and professional fees of $0.8 million. Net loss. Net loss and net loss per share for the year ended December 31, 2024 was $39.8 million and $0.93, respectively, compared to a net loss and net loss per share of $28.5 million and $2.78, for the comparable period in 2023. About VYNE Therapeutics Inc. VYNE is a clinical-stage biopharmaceutical company focused on developing differentiated therapies to treat chronic inflammatory and immune-mediated conditions with high unmet need. VYNE's unique and proprietary BET inhibitors, which comprise its InhiBET™ platform, are designed to overcome limitations of early generation BET inhibitors by leveraging alternative routes of administration and enhanced selectivity. For more information about VYNE Therapeutics Inc. or its product candidates, visit www.vynetherapeutics.com. VYNE may use its website to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor VYNE’s website in addition to following its press releases, filings with the U.S. Securities and Exchange Commission, public conference calls, and webcasts. Investor Relations:John FrauncesLifeSci Advisors, LLC917-355-2395jfraunces@lifesciadvisors.com Tyler ZerondaVYNE Therapeutics Inc.908-458-9106Tyler.Zeronda@VYNEtx.com Media Relations: Mike BeyerSam Brown Inc.312-961-2502mikebeyer@sambrown.com Cautionary Statement Regarding Forward-Looking Statements This release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the clinical development of, and timing for reporting top-line results from trials of, repibresib and VYN202, the impact of the reported top-line results from trials on clinical development, VYNE's participation in upcoming conferences, VYNE’s projected cash runway, and other statements regarding the future expectations, plans and prospects of VYNE. All statements in this press release which are not historical facts are forward-looking statements. Any forward-looking statements are based on VYNE’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions that could cause actual results to differ materially and adversely from those set forth or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: VYNE’s ability to successfully develop its product candidates; the timing of commencement of future preclinical studies and clinical trials; VYNE’s ability to complete and receive favorable results from clinical trials of its product candidates; VYNE’s ability to obtain additional funding, either through equity or debt financing transactions or collaboration arrangements; and VYNE’s ability to comply with various regulations applicable to its business. For a discussion of other risks and uncertainties, and other important factors, any of which could cause VYNE’s actual results to differ from those contained in the forward-looking statements, see the section titled “Risk Factors” in VYNE’s Annual Report on Form 10-K for the year ended December 31, 2024, and VYNE’s other filings from time to time with the U.S. Securities and Exchange Commission. Although VYNE believes these forward-looking statements are reasonable, they speak only as of the date of this announcement and VYNE undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Given these risks and uncertainties, you should not rely upon forward-looking statements as predictions of future events. Third-party products and company names mentioned herein may be the trademarks of their respective owners.

宝子们，有没有过这样的经历：精心准备出门约会或参加重要聚会，临出门前对着镜子一看，脸上不知何时冒出了红斑，还有些小丘疹若隐若现，瞬间心情就像坠入了冰窖。又或者在日常工作中，总感觉面部灼热、瘙痒，让人坐立不安，严重影响了生活和社交。其实，这可能就是玫瑰痤疮在作祟。这种慢性炎症性皮肤病，困扰着许多人。 传统治疗手段如使用甲硝唑、壬二酸、异维A酸等药物，虽有一定疗效，但往往伴随着诸如皮肤瘙痒、灼烧感、潜在的视网膜病变及致畸风险等副作用。激光疗法虽能缓解红斑症状，但对于丘疹脓疱性病变效果不佳，且费用高昂。 近期一项发表在Int Immunopharmacol的研究Activation of aryl hydrocarbon receptor ameliorates degranulation of LL-37 induced mast cells in rosacea through enhancing autophagy为玫瑰痤疮治疗带来了新的希望。研究发现，肥大细胞在玫瑰痤疮的发病过程中起着关键作用。在患者的皮肤病变部位，肥大细胞数量显著增加，这些被激活的肥大细胞会释放出多种细胞因子，如白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）、基质金属蛋白酶（MMP9）等，这些细胞因子进一步加剧炎症反应，推动病情发展。 在本研究中，科研人员以肥大细胞（RBL-2H3）为研究对象，用LL-37处理模拟玫瑰痤疮环境。随后加入AhR激动剂（tapinarof），并利用自噬激动剂（RAPA）和抑制剂（CQ）探究其机制。 研究结果显示，在细胞脱颗粒与炎症因子表达方面，LL-37处理后，肥大细胞内的脱颗粒标记物Cma1和Tpsab1在蛋白和mRNA水平上随时间显著上升，24小时达到高峰，同时炎症因子IL-6、MMP9和TNF-α的mRNA表达也在24小时明显增加。而tapinarof处理24小时后，Cma1和Tpsab1的蛋白及mRNA表达大幅降低，IL-6、MMP9和TNF-α的mRNA表达也显著下降，表明tapinarof能有效抑制肥大细胞脱颗粒及炎症反应。 观察自噬标记物变化发现，随着tapinarof浓度增加，Western blot检测发现LC3B-I逐渐向LC3B-II转化，p62含量减少。经Image J软件分析，证实自噬在tapinarof作用下增强。免疫荧光染色显示，tapinarof+LL-37组中LC3B-II点状聚集数量比仅LL-37诱导的肥大细胞明显增多，进一步证明tapinarof促进自噬。 在自噬调节剂与tapinarof协同关系方面，对于自噬激动剂RAPA，浓度高于5 μM会降低细胞活力，但5 μ MRAPA与10 μM tapinarof共同作用于16 μM LL-37诱导的肥大细胞24小时或48小时后，Western blot结果显示LC3B-II表达随tapinarof处理时间延长而上升，验证了自噬增强效果。 对于自噬抑制剂CQ，浓度高于5 μM显著降低细胞活力，在16 μM LL-37处理24小时的细胞中，先加5 μM CQ处理4小时再用tapinarof处理24小时后，与未加CQ组相比，CQ仅部分抑制tapinarof诱导的自噬，且RT-qPCR分析表明CQ使Cma1、Tpsab1、MMP9、TNF-α和IL-6表达增加，证实自噬在tapinarof缓解炎症中起关键作用，且CQ可逆转tapinarof的部分抗炎效果。 图 1. tapinarof减轻肥大细胞中的玫瑰痤疮样炎症 图 2. tapinarof诱导自噬以减少肥大细胞中的玫瑰痤疮样炎症反应 此前研究已表明AhR激活可改善小鼠玫瑰痤疮样皮疹并抑制相关细胞信号通路，此次研究进一步明确了其通过增强自噬减轻肥大细胞脱颗粒从而缓解玫瑰痤疮的机制。尽管目前该研究仅处于体外实验阶段，但已为玫瑰痤疮的治疗研究指明了新方向。未来还需开展动物及临床研究进一步验证，若能成功转化为临床应用，有望为玫瑰痤疮患者带来更有效、更安全的治疗方案，极大地改善患者的生活质量，推动皮肤病治疗的发展。 参考文献： Chen S, Hu H, Wu J, et al. Activation of aryl hydrocarbon receptor ameliorates degranulation of LL-37 induced mast cells in rosacea through enhancing autophagy. Int Immunopharmacol. Published online December 29, 2024. doi:10.1016/j.intimp.2024.113910 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！ 点击下方「阅读原文」，前往生物谷官网查询更多生物相关资讯~