DEFB1

Preclinical studies suggest VYN202 has the potential to be the most potent and selective BET inhibitor in development VYN202 has demonstrated a potent anti-inflammatory and anti-fibrotic effect in multiple validated preclinical models of autoimmune disease IND-enabling studies are ongoing in anticipation of an IND filing by year-end BRIDGEWATER, N.J., May 01, 2023 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced the selection of a development candidate for its oral BD2-selective bromodomain and extra-terminal (“BET”) inhibitor program, VYN202, for the treatment of immuno-inflammatory conditions. The lead candidate was selected by VYNE from a library of BD2-selective BET inhibitors that VYNE exclusively licensed from Tay Therapeutics following the receipt of a robust package of preclinical data, including encouraging results from well-validated animal models in various autoimmune disorders. VYNE also obtained rights to several other BD2-selective BET inhibitor compounds with attractive molecular profiles that the Company may develop, at its discretion, in the future. “After extensive testing of multiple compounds across several well-validated preclinical models, we are pleased to have selected a development candidate for VYN202, which is specifically designed to be delivered orally, for the treatment of immuno-inflammatory conditions,” said David Domzalski, President and Chief Executive Officer of VYNE. “We are encouraged by the potential class-leading data and profile demonstrated by VYN202 in preclinical studies to date, and we look forward to further progressing our IND-enabling program and advancing VYN202 into clinical development.” VYN202 targets BET proteins that play key roles in regulating gene transcription via epigenetic interaction (“reading”) with specific chemical motifs on H3 and H4 histone N-terminal tail domains that extend beyond a nucleosome unit. As epigenetic readers, BET proteins are super-enhancers of gene transcription that drive the hyperactive production of many pro-inflammatory proteins that characterize autoimmune and autoinflammatory diseases. Recent research has highlighted BET proteins as important contributors in regulating both B cell and T cell activity and, in preclinical models, BET inhibitors have demonstrated the potential to treat a range of immuno-inflammatory and fibrotic diseases.1,2 Early generation systemic BET inhibitors that inhibit both the BD1 and BD2 domains of BET proteins (pan-BD BET inhibitors) have historically been associated with gastrointestinal and hematological toxicities, such as thrombocytopenia (low platelet counts) in clinical trials.3 BD1 functionality has been associated with the regulation of genes responsible for maintaining homeostatic cellular processing, and that selectively inhibiting BD1 or BD1 and BD2 may contribute to unwanted dose limiting toxicities.1,4 VYN202 is designed to be significantly more selective in inhibiting BD2 than BD1 with the objective of limiting the potential of similar safety concerns associated with earlier pan-BD BET inhibitors. VYNE has initiated IND-enabling studies for VYN202 and intends to submit an IND by year-end. Under VYNE’s license agreement with Tay, VYNE has exclusive worldwide rights to the compounds in its InhiBET™ platform, including VYN202, for all human disease applications. Gilan et al, Science., 2020 April 24; 368(6489): 387Kawahito et al, Pulm. Pharma. & Therp., 2021; 70:102057Sun et al, Front. Pharmacol., 2021; 11:621093Faivre et al, Nature, 2020; 578:306 About VYNE Therapeutics Inc. VYNE’s mission is to improve the lives of patients by developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions. The Company’s unique and proprietary bromodomain & extra-terminal (BET) domain inhibitors, which comprise its InhiBET™ platform, includes a locally administered pan-BET inhibitor (VYN201) and an orally available BD2-selective BET inhibitor (VYN202) that were licensed from Tay Therapeutics Limited. 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. 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 VYNE’s plans and development timelines for VYN202, including the submission of an IND by year end, VYNE’s InhiBET™ platform, 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 non-clinical studies and clinical trials; VYNE’s ability to enroll patients and successfully progress, complete, and receive favorable results in, clinical trials for its product candidates; VYNE’s intentions and its ability to obtain additional funding, either through equity or debt financing transactions or collaboration arrangements; disruptions related to COVID-19 or another pandemic, epidemic or outbreak of a contagious disease, on the ability of VYNE’s suppliers to manufacture and provide materials for VYNE’s product candidates, initiating and retaining patients in clinical trials, operating results, liquidity and financial condition; developments and projections relating to competitors and the pharmaceuticals industry, including competing drugs and therapies; the timing or likelihood of regulatory filings and approvals or clearances for product candidates; VYNE’s ability to comply with various regulations applicable to its business, including Nasdaq continued listing rules; VYNE’s ability to create intellectual property and the scope of protection it is able to establish and maintain for intellectual property rights covering its product candidates, including the projected terms of patent protection; risks that any of VYNE’s patents may be held to be narrowed, invalid or unenforceable or one or more of VYNE’s patent applications may not be granted and potential competitors may also seek to design around VYNE’s granted patents or patent applications; the timing, costs or results of litigation, including litigation to protect its intellectual property; VYNE’s ability to successfully challenge intellectual property claimed by others; estimates of VYNE’s expenses, capital requirements, its needs for additional financing and its ability to obtain additional capital on acceptable terms or at all; VYNE’s ability to attract and retain key scientific or management personnel; and VYNE’s expectations regarding licensing, business transactions and strategic operations. 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, 2022, as well as discussions of potential risks, uncertainties, and other important factors in VYNE’s subsequent filings 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. Investor Relations: John FrauncesLifeSci Advisors, LLC917-355-2395jfraunces@lifesciadvisors.com Tyler ZerondaVYNE Therapeutics Inc.908-458-9106Tyler.Zeronda@vynetx.com

Researchers have identified potent, highly specific compounds that interfere with bromodomain (BD)-containing proteins involved in cancer. The compounds, called BET BD1-inhibitors, are a starting point in the development of potentially more effective anti-cancer drugs with less side effects. Researchers at Baylor College of Medicine and Texas Children's Hospital have identified potent, highly specific compounds that interfere with bromodomain (BD)-containing proteins involved in cancer. The compounds, called BET BD1-inhibitors, are a starting point in the development of potentially more effective anti-cancer drugs with less side effects. The team reports in the Proceedings of the National Academy of Sciences that the novel approach developed at Baylor's Center for Drug Discovery (CDD) enables the screening of billions of compounds at once and precisely identifies potent drug-like molecules that bind to the cancer protein of interest. One key advantage of this approach is the price tag -- these screens are a fraction of the cost of previous methods. In laboratory experiments with cells, the new BD1-inhibitors had marked anti-leukemic activity. "BD-containing proteins are implicated in cancer, inflammation, infectious diseases and metabolic disorders and have emerged as potential drug targets in a variety of diseases," said Dr. Joanna Yi, one of the lead authors and assistant professor of pediatric hematology/oncology at Baylor and Texas Children's. "Over a decade of research has shown that BD-inhibitors can help control cancer growth; however, when tested in clinical trials some had side effects and limited efficacy, halting further clinical development. This has encouraged our group to search for more effective BD-inhibitors." The researchers focused on identifying inhibitors specific for the first bromodomains (BD1) in the bromodomain and extra-terminal (BET) subgroup of human proteins. Recent research has shown that BD1 is very important in driving cancer, the researchers explained. "To identify novel BD1-inhibitors, we took advantage of an innovative, faster and more cost-effective drug discovery tool called DNA-Encoded Chemistry Technology, which enables us to screen billions of compounds," said first author Dr. Ram K. Modukuri, a staff scientist in the Department of Pathology & Immunology and the CDD at Baylor. The more commonly used method for discovering drugs, called high throughput screening, involves screening at most a million compounds in individual test tubes. In contrast, by using DNA-Encoded Chemistry Technology, the team was able to screen 4 billion DNA-encoded molecules all in one test tube against BD1 to find one that would bind to it with high specificity when compared to binding to other bromodomains. "DNA-Encoded Chemistry Technology enabled us to identify CDD-724, a compound that is highly selective for BD1. It is about 2,000 times better at inhibiting BD1 than at inhibiting other human bromodomains, including the second bromodomain (BD2) of the BET subgroup," Modukuri said. How does DNA-Encoded Chemistry Technology work? "The DNA-Encoded Chemistry Technology process involves a simultaneous screen of billions of molecules, each one tagged with a DNA barcode," said corresponding author Dr. Martin Matzuk, professor and chair of pathology and immunology and director of the Center for Drug Discovery at Baylor. "The molecules that 'stick' to the protein (in this case BD1) are identified by sequencing of their attached DNA barcode. This is a rapid drug discovery screen, and our study demonstrates its enormous potential to find unique candidates for anti-cancer drugs." To better understand why their BD1-inhibitor stands out over other inhibitors, the team joined forces with Dr. Choel Kim, associate professor of pharmacology and chemical biology, who also is a member of the CDD and the Dan L Duncan Comprehensive Cancer Center at Baylor. The researchers conducted 3D molecular studies to determine the precise location on the BD1 protein to which the BD1-inhibitor binds. They discovered that the BD1-inhibitor binds to a shallow area on the BD1 protein -- this is not seen in other BD1 inhibitors. This finding represents a new opportunity to explore other BD1-selective inhibitors. "We are searching for highly specific, potent, effective compounds with reduced side effects that we can bring to the clinic," said Yi, also a member of Baylor's CDD and the Dan L Duncan Comprehensive Cancer Center. "We are ready to test these compounds in animal models to evaluate their safety and efficacy, which is one step closer to clinical trials." Zhifeng Yu, Zhi Tan, Hai Minh Ta, Melek Nihan Ucisik, Zhuang Jin, Justin L. Anglin, Kiran L. Sharma, Pranavanand Nyshadham, Feng Li, Kevin Riehle, John C. Faver, Kevin Duong, Sureshbabu Nagarajan, Nicholas Simmons, Stephen S. Palmer, Mingxing Teng and Damian W. Young also contributed to this work. The authors are affiliated with Baylor College of Medicine and/or Texas Children's Hospital. This work is supported by the Bill and Melinda Gates Foundation (INV-001902), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD087157), the Welch Foundation (H-Q-0042), and a Core Facility Support Award from the Cancer Prevention Research Institute of Texas (CPRIT) (RP160805). Further support was provided by NIH grants (5K12CA090433-17, R01DK121970, R61HD099995, S10RR25528, S10RR028976, and S10OD027000), Alex's Lemonade Stand Foundation, the Curing Kids Cancer Foundation, CURE Childhood Cancer Foundation, and CPRIT grants (RR220012 and RR220039).