VYNE Therapeutics Announces Positive First-In-Human Pharmacokinetic and Hematology Data from Phase 1a Single and Multiple Ascending Dose Trial for Novel Pan-Bromodomain BET Inhibitor VYN201

• No quantifiable VYN201 plasma concentrations above the assay lower limit of quantification supports “soft” drug approach for topical pan-BD BET inhibitor

• All hematological parameters, including platelet counts, were within normal ranges, a finding which has not previously been observed with systemically administered pan-BD BET inhibitors
• Topline Phase 1b results in patients with nonsegmental vitiligo expected in mid-2023

BRIDGEWATER, N.J., March 30, 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 positive first-in-human pharmacokinetic and hematology data from its Phase 1a single and multiple ascending dose trial for its investigational novel BET inhibitor, VYN201. In February 2023, the Company announced positive preliminary safety and tolerability data from the trial.

The Phase 1a portion of the trial included comprehensive pharmacokinetic sampling to ascertain the exposure to topically-applied VYN201 from single and repeat treatment of VYN201 over five ascending dose cohorts. Results have shown that there were no quantifiable VYN201 plasma concentrations above the assay lower limit of quantification (0.25ng/ml).

Inhibiting the functionality of the bromodomain 1 (BD1) subunit of BET proteins is believed to disrupt homeostatic gene regulation. This can lead to potential clinical safety concerns such as thrombocytopenia (low platelet count), a known dose-limiting adverse event for systemically administered pan-BD BET inhibitors.¹ In the Phase 1a trial, there was no evidence of low or lower platelet counts at any timepoint for any dose cohort. The assay lower limit of quantification (LLOQ) of 0.25ng/ml is 720-fold below the free half maximal effective concentration (EC50) for VYN201 against the BD1 domain of the BET protein, BRD4. There was no effect on other assessed clinical hematological parameters.

“These data, showing minimal systemic exposure of VYN201 with no effect on platelet counts, mark an important milestone in our development of VYN201 as a topically-administered pan-BD BET inhibitor,” said Dr. Iain Stuart, Chief Scientific Officer of VYNE. “These findings support our “soft” drug approach to treating patients with nonsegmental vitiligo, particularly in light of some of the potential safety concerns with current topical therapies and oral therapies in development.”

Enrollment in the Phase 1b portion of the trial is ongoing and the Company expects to report topline results in mid-2023.

About the Phase 1a/b Trial in Healthy Volunteers and Patients with Nonsegmental Vitiligo
In the Phase 1a portion of the study, single ascending and multiple ascending doses of VYN201 were applied topically once daily to 30 healthy volunteers in five dose cohorts (0.025%, 0.1%, 0.5%, 1.0% and 2.0% ointment strengths) over a two-week treatment period with a one-week safety follow-up visit to evaluate the safety, tolerability and pharmacokinetics of VYN201. The safety and tolerability results are summarized below:

• 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.
• No healthy volunteers withdrew from the trial for any reason.

Based on the Phase 1a results, VYNE selected 0.5%, 1.0% and 2.0% ointment strengths for evaluation in the ongoing Phase 1b study. In this portion of the study, up to 30 patients with a clinical diagnosis of non-segmental vitiligo will receive VYN201 once daily in three dose cohorts. The primary objective of the Phase 1b portion of the study will be to evaluate the safety and pharmacokinetics of VYN201. Exploratory efficacy of VYN201 in non-segmental vitiligo patients will also be evaluated, including F-VASI, pharmacodynamic biomarkers and clinical photography.

About VYN201 and Vitiligo
VYN201 is a locally-administered pan-bromodomain BET inhibitor, designed as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure. To date, VYN201 has produced consistent reductions in pro-inflammatory and disease-related biomarkers, improvements in disease severity and a demonstrated local activity through several preclinical models. The Company believes that these data suggest potential broad utility for VYN201 across multiple routes of administration. 

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% of the world population.² There is currently only one FDA-approved product for the treatment of vitiligo. Non-segmental vitiligo is the most common type of vitiligo.

About BET Inhibitors
BET proteins play a key role in regulating gene transcription via epigenetic interactions (“reading”), and recent research has determined a key role for these BET proteins in regulating B cell and T cell activation and subsequent inflammatory processes. As epigenetic readers, BET proteins regulate the recruitment of transcriptional factors that are key to the production of several pro-inflammatory cytokines. BET inhibitors (BETi) have the potential to treat a range of immuno-inflammatory and fibrotic diseases by blocking pro-inflammatory cytokine transcription with additional potential in myeloproliferative neoplastic disorders.

1. O’Neil et al, Clin Cancer Res. (2019); 25(21): 6309-6319
2. Rosmarin et al, Lancet (2020);396:110-120

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 platform includes lead programs, VYN201 (locally administered pan-BETi), and VYN202 (orally available selective-BETi), and access to a library of small molecule BET inhibitors for the potential treatment of immuno-inflammatory conditions 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 the receipt of topline results in VYNE’s phase 1 trial of VYN201, VYNE’s InhiBET™ BET inhibitor 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 ability to exercise its exclusive option with respect to an oral BET inhibitor candidate pursuant to the terms of the option agreement with Tay Therapeutics Limited; 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; the regulatory approval process for VYNE’s product candidates, including any delay or failure in obtaining requisite approvals; the potential market size of treatments for any diseases and market adoption of products, if approved or cleared for commercial use, by physicians and patients; 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; VYNE’s defense of any litigation that may be initiated against it; VYNE’s expectations regarding licensing, business transactions and strategic operations; VYNE’s future financial performance and liquidity; and volatility in VYNE’s stock price may result in rapid and substantial increases or decreases in the stock price that may or may not be related to the company’s operating performance or prospects. 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 Fraunces
LifeSci Advisors, LLC
917-355-2395
jfraunces@lifesciadvisors.com

Tyler Zeronda
VYNE Therapeutics Inc.
908-458-9106
Tyler.Zeronda@vynetx.com