Repibresib

Trial Did Not Meet Primary Endpoint or Key Secondary Endpoint of F-VASI50 and F-VASI75 Nominally Statistically Significant Effects Observed in Key Secondary and Exploratory Endpoints of Change from Baseline in F-VASI and T-VASI at 3% Concentration Company Will Terminate Extension Phase of Trial and Seek External Partner for Continued Development of Repibresib BRIDGEWATER, N.J., July 30, 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 topline results from its Phase 2b trial evaluating Repibresib gel in nonsegmental vitiligo. The trial, which evaluated 177 subjects, 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. The trial also missed a key secondary endpoint of F-VASI75. However, the trial showed a nominally statistically significant treatment effect for the highest dose cohort in a key secondary endpoint, percent change-from-baseline (CFB) in F-VASI score at week 24 compared to vehicle (Repibresib 3%: -43.6% v. Vehicle: -25.6%), and an exploratory endpoint of percent CFB in T-VASI score at week 24 compared to vehicle (Repibresib 3%: -28.3% v. Vehicle: -16.2%). In evaluating the results of the trial, the Company believes the results were impacted by an unusually high vehicle effect and further impacted by a higher-than-expected dropout rate in the active arms of the trial relative to vehicle (Repibresib 3%: 36.6%; Repibresib 2%: 30.2%; Repibresib 1%: 26.1% and vehicle: 10.6%). Based on these data, the company will discontinue treatment in the ongoing extension phase of the trial and will terminate the trial. The Phase 2b trial was a randomized double-blind, vehicle-controlled, multi-center trial that evaluated the safety and efficacy of Repibresib dosed once daily (QD) at 1%, 2% and 3% concentrations, versus vehicle in 177 subjects (mITT population) with nonsegmental vitiligo. The trial was conducted at 45 sites in North America and assessed various efficacy endpoints, including the primary endpoint of the proportion of subjects achieving F-VASI50 at Week 24 versus vehicle, as well as key secondary endpoints, which included the proportion of subjects achieving F-VASI75 at Week 24, percent CFB in F-VASI score at week 24 and exploratory endpoints including percent CFB in T-VASI score at week 24. “We are disappointed with the results of our Phase 2b trial, which were impacted by an unexpectedly high treatment effect in the vehicle arm and a high discontinuation rate in the active arms,” said David Domzalski, President and Chief Executive Officer of VYNE. “Although we missed our F-VASI50 and F-VASI75 endpoints, we did see a meaningful reduction in the percent change from baseline in both F-VASI and T-VASI for our highest dose and are conducting a thorough evaluation of the full dataset to analyze any other data that may inform the results and our strategic next steps. Vitiligo remains an area of significant unmet need and we are grateful to the patients, investigators, and clinical staff who participated in the trial. Despite this outcome, we remain confident in the potential of our InhiBET™ BET inhibitor platform as a promising and innovative mechanistic approach for the treatment of a broad range of serious immune-mediated diseases. We intend to seek a development and commercialization partner for Repibresib and we will provide an update on our plans, including those for our oral BET inhibitor VYN202, in the coming weeks.” While the Company has not finalized its full financial results for the quarter ended June 30, 2025, the Company expects to report that it had cash, cash equivalents and investments of approximately $39.6 million (unaudited) as of June 30, 2025. Primary endpoint: proportion of subjects achieving F-VASI50 at Week 24 versus vehicle in modified intent to treat population (mITT) Endpoint at Week 24Repibresib 3%Repibresib 2%Repibresib 1%Vehicle(N=41)(N=43)(N=46)(N=47)Proportion of Subjects Achieving F-VASI5019.5%16.3%17.4%23.4%P-Value0.12450.64970.9718 Key Secondary and Exploratory Endpoints Proportion of subjects achieving F-VASI75 at Week 24 (mITT) Endpoint at Week 24Repibresib 3% Repibresib 2% Repibresib 1% Vehicle(N=41)(N=43)(N=46)(N=47)Proportion of Subjects Achieving F-VASI759.8%7.0%10.9%6.4%P-Value0.14680.40960.2946 Percent Change from Baseline (% CFB) in F-VASI at Week 24 (mITT) Endpoint at Week 24Repibresib 3% Repibresib 2% Repibresib 1% Vehicle(N=41)(N=43)(N=46)(N=47)Mean Percent Change from Baseline in F-VASI, % (SD)-43.6 (5.7)-25.7 (5.7)-30.2 (5.2)-25.6 (4.9)P-Value0.00200.98920.4002 Percent Change from Baseline (% CFB) in T-VASI at Week 24 (mITT) Endpoint at Week 24Repibresib 3% Repibresib 2% Repibresib 1% Vehicle(N=41)(N=43)(N=46)(N=47)Mean Percent Change from Baseline in T-VASI, % (SD)-28.3 (6.1)-15.2 (6.1)-16.4 (5.2)-16.2 (4.9)P-Value0.04360.87570.9670 Safety and TolerabilityThere was a higher rate of treatment emergent adverse events (TEAE) for subjects receiving Repibresib gel compared to vehicle. The most common TEAEs (>5%) were cutaneous in nature. The most frequent adverse event was application site pain (Repibresib 3%: 14.0%; Repibresib 2%: 5.9%; Repibresib 1%: 13.7%; Vehicle: 3.8%). There were 8 subjects receiving Repibresib gel that discontinued due to an AE compared to none in the vehicle. The majority of skin-related TEAEs were mild in severity and resolved during study conduct (76.0% “Mild”, 23.7% “Moderate” and 0.2% “Severe”) and there was no clear dose-dependent increase in frequency of skin-related TEAEs. There was one treatment emergent serious adverse event, cholelithiasis without obstruction, not drug related in the Repibresib 1% cohort, and there was no increased risk of thrombocytopenia or GI-related serious adverse events. About Repibresib Repibresib is a pan-bromodomain BET inhibitor designed to be locally administered as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways, while providing low systemic exposure. Repibresib has produced consistent reductions in pro-inflammatory and disease-related biomarkers and improvements in disease severity in several preclinical models (using several different routes of administration). About VYN202VYN202 is an innovative, oral small molecule BET inhibitor that has potential class-leading selectivity and potency for BD2 vs. BD1. By maximizing BD2 selectivity, VYNE believes VYN202 has the potential to be a differentiated, more conveniently administered, non-biologic treatment option for both acute control and chronic management of immuno-inflammatory indications, in which the damaging effects of unrestricted inflammatory signaling activity are common. 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 Cautionary Statement Regarding Forward-Looking StatementsThis 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 VYNE’s product candidates 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, including the Company’s intention to seek a development and commercialization partner for repibresib, timing of an update on the Company’s plans for repibresib and the expectations around its cash position as of June 30, 2025. The Company’s cash estimate is preliminary and is subject to change pending the actual results of, and completion of, the Company’s condensed consolidated financial statements for the quarter ended June 30, 2025. Additional information and disclosures would be required for a more complete understanding of the Company’s financial position and results of operations as of June 30, 2025. The Company’s independent registered public accounting firm has not reviewed or performed any procedures with respect to this preliminary information and, accordingly, does not express an opinion or any other form of assurance about them. Any forward-looking statements in this release 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 find a partner for repibresib; 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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, 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

Cardiff Oncology's stock plunged nearly 28% on Wednesday despite the company touting "positive" results from the latest readout of its Phase II trial testing PLK1 inhibitor onvansertib in first-line RAS-mutated metastatic colorectal cancer (mCRC).Participants in the CRDF-004 study received standard treatment (FOLFIRI or FOLFOX, plus bevacizumab) and were randomised to one of six groups, including onvansertib at 20 mg or 30 mg, both on top of standard care, or standard care alone. The latest readout is based on 110 patients with a July 8 data cutoff, up from Cardiff's initial December data release that showed promising signals in 30 patients. In that earlier analysis, the high-dose onvansertib arm had demonstrated a 64% objective response rate (ORR), nearly double the 33% seen with standard therapy.Narrowing gapHowever, in the expanded dataset, the response gap narrowed: the 30-mg group had a 59% ORR, compared to 43% in the control arm. Confirmed responses were 49% and 30%, respectively.The shrinking margin may have disappointed investors. Still, analysts at Jefferies recently noted that a 20% response delta would generally be considered encouraging, though they cautioned that meaningful efficacy data, including an early look at durability signals, likely wouldn't emerge until later in the year."The totality of the data…strengthens the initial findings from our December 2024 data release in a significantly larger patient population, compares favourably to previous practice-changing Phase III trials," said Roger Sidhu, chief medical officer. "Furthermore, early PFS (progression-free survival) data shows a trend favouring the 30-mg dose of onvansertib vs. control."CEO Mark Erlander said the data "positions us to engage in discussions with the FDA as we advance toward our registrational CRDF-005 trial."Failed vitiligo studyVYNE Therapeutics suffered a steeper drop, with shares tumbling more than 71% on Wednesday after the company said its experimental vitiligo treatment failed to meet primary and key secondary endpoints in a Phase IIb trial. CEO David Domzalski said VYNE would seek an external partner to continue development of repibresib gel, a pan-bromodomain BET inhibitor designed to be locally administered as a 'soft' drug to address diseases involving inflammatory cell signaling pathways, while providing low systemic exposure.The trial evaluated 177 patients with nonsegmental vitiligo, testing three concentrations of repibresib gel against vehicle. The study failed to achieve its primary endpoint – the proportion of patients showing at least 50% improvement on Facial Vitiligo Area Scoring Index (F-VASI50) at 24 weeks – with response rates ranging from 16.3% to 19.5% for the active doses compared to 23.4% for placebo. The trial also missed a key secondary endpoint of F-VASI75.However, the highest 3% dose showed a nominally statistically significant reduction in F-VASI scores from baseline, with a 43.6% improvement versus 25.6% for vehicle.Domzalski said the results "were impacted by an unexpectedly high treatment effect in the vehicle arm and a high discontinuation rate in the active arms." Despite the setback, he added, "We intend to seek a development and commercialization partner for repibresib and we will provide an update on our plans, including those for our oral BET inhibitor VYN202, in the coming weeks."In April, the FDA placed a clinical hold on the company's Phase Ib trial of VYN202 after a non-clinical toxicology study in dogs revealed signs of testicular toxicity, but recently lifted the hold for female patients at some lower doses.Alzheimer's biomarkersMeanwhile NewAmsterdam Pharma may have offered a bit of a bright spot amid the gloom. The company said its experimental cholesterol treatment obicetrapib demonstrated statistically significant reductions in key Alzheimer's disease biomarkers in a subset analysis of patients at highest risk for the neurodegenerative condition. Detailed findings from the Phase III BROADWAY trial were shared at the Alzheimer's Association International Conference (AAIC), building on preliminary results disclosed in June that suggested the CETP inhibitor could slow the accumulation of plasma p-tau217.The study was originally designed to evaluate obicetrapib's ability to lower LDL cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia. In December, the company reported that the drug achieved a 33% reduction in LDL-C, meeting the primary endpoint. However, a prespecified analysis of 1515 patients whose ApoE status could be determined revealed possible neurological benefits as well, including among the 367 carriers of the ApoE4 gene variant.In patients carrying two copies of the ApoE4 gene, obicetrapib reduced p-tau217 levels by 20.5% (p=0.01) over 12 months compared to placebo. Additional reductions observed in other neurodegeneration biomarkers including a 17.3% (p=0.02) decrease in neurofilament light chain and a nearly 13.7% (p=0.06) reduction in p-tau181."This is especially important in ApoE4 gene carriers – a group that represents over a quarter of the population and faces a heightened risk for this disease," said CEO Michael Davidson. "Combined with its LDL-C lowering benefits observed in multiple clinical trials, obicetrapib may offer a unique opportunity to reduce both neurodegenerative and heart disease risks."The company says it plans to discuss these findings with regulatory authorities to determine potential development pathways for a "novel, upstream approach" for Alzheimer's prevention.