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BRIDGEWATER, N.J., June 13, 2024 (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 that the first healthy volunteers have been dosed in the Phase 1a trial of VYN202. VYN202 is an oral small molecule BD2-selective bromodomain and extra-terminal domain (BET) inhibitor that is being developed for the treatment of immuno-inflammatory diseases. Top-line data are expected in the second half of 2024.

“We are pleased to announce the initiation of the first-in-human clinical trial of VYN202, a highly selective and potent orally administered BET inhibitor. In preclinical testing, VYN202 achieved consistent improvements in disease severity across a variety of inflammatory and fibrotic models as well as reductions in pro-inflammatory and disease-related biomarkers,” said David Domzalski, President and CEO of VYNE. “We believe VYN202 has significant potential as a treatment option for a broad range of immune-mediated diseases, and we look forward to reporting top-line data from the Phase 1a trial in the second half of this year.”

The Phase 1a trial is a first-in-human double-blind, placebo-controlled study in healthy volunteers and consists of single ascending dose (SAD) and multiple ascending dose (MAD) components. The trial is currently expected to enroll approximately 64 healthy adult subjects into five SAD and three MAD cohorts to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VYN202.

“Early generation BET inhibitors show similar affinity to both BD1 and BD2 bromodomains of BET proteins that has been implicated in both gastrointestinal and hematologic dose limiting toxicities,” said Dr. Iain Stuart, Chief Scientific Officer of VYNE. “We believe VYN202’s high potency and selectivity towards the BD2 bromodomain of BET proteins may result in an improved benefit-risk profile when treating immuno-inflammatory diseases. Following highly encouraging preclinical data, we are eager to evaluate the clinical safety, tolerability, pharmacokinetics and pharmacodynamics of VYN202 to further inform our future clinical development plans.”

BRIDGEWATER, N.J., June 05, 2024 (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 that the first subject has been dosed in a Phase 2b trial evaluating VYN201 in subjects with either active or stable nonsegmental vitiligo. VYN201 is a novel pan-bromodomain and extra-terminal domain (BET) inhibitor designed for local administration. Top-line data from the 24-week vehicle-controlled treatment period are expected in mid-2025.

The randomized, double-blind, vehicle-controlled trial will evaluate the safety and efficacy of once-daily VYN201 topical gel in three dose cohorts (1%, 2% and 3% concentrations) compared to vehicle for 24 weeks. A total of approximately 160 subjects will be randomized at a 1:1:1:1 ratio. Following the 24-week treatment period, subjects in the active treatment arms will continue for an additional 28 weeks, and subjects in the vehicle group will be equally re-randomized to receive VYN201 1%, 2% or 3% gel for an additional 28 weeks. The primary efficacy endpoint of the trial is 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, with additional secondary endpoints of F-VASI and Total VASI (T-VASI) at weeks 24 and 52.

“Dosing the first subject in the Phase 2b trial for vitiligo is an important milestone for the VYN201 program and our Company,” said David Domzalski, President and CEO of VYNE. “In our prior Phase 1b trial, VYN201 demonstrated a significant clinical response with a rapid onset of action and a favorable safety and tolerability profile, including low systemic exposure. We believe that VYN201 has the potential to become a valuable and differentiated therapy for patients with vitiligo. We look forward to reporting top-line data from the 24-week treatment period in mid-2025.”

BRIDGEWATER, N.J., May 06, 2024 (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 clearance of its Investigational New Drug application (“IND”) by the U.S. Food and Drug Administration for VYN202, an oral BD2-selective BET inhibitor. VYNE plans to initiate a first-in-human Phase 1a single ascending dose/multiple ascending dose (“SAD/MAD”) trial in healthy volunteers this quarter and expects to report top line results from the SAD/MAD trial in the second half of this year.

“VYN202 is a highly selective and potent orally administered BET inhibitor that we believe has significant potential as a treatment option for autoimmune diseases. Clearance of the IND for VYN202 marks a major step forward in this effort,” said David Domzalski, President and CEO of VYNE. “We look forward to initiating the Phase 1a trial in the coming weeks to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VYN202.”

The VYN202 Phase 1a trial is a double-blind, placebo-controlled study in healthy volunteers and consists of SAD and MAD components. The study is expected to enroll approximately 64 healthy adult subjects into five SAD and three MAD cohorts to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VYN202. If the Phase 1a portion of the trial is successfully completed, VYNE plans to initiate Phase 1b trials in subjects with moderate-to-severe plaque psoriasis and moderate-to-severe adult-onset rheumatoid arthritis, with top line results anticipated in the second half of 2025.

BRIDGEWATER, N.J., Jan. 10, 2024 (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 new biomarker data from the previously completed Phase 1b trial in patients with nonsegmental vitiligo. The data show that BET inhibitor, VYN201, had a positive effect on multiple disease-associated biomarkers.

Positive clinical data from the Phase 1b trial were announced in October 2023. The trial was a 16-week open-label study assessing the safety, tolerability, pharmacokinetics, and exploratory efficacy of once-daily topical VYN201 in 29 patients with a clinical diagnosis of active nonsegmental vitiligo, in three dose cohorts (0.5%, 1.0% and 2.0% strengths). Enrolled subjects had two, non-facial active vitiligo lesions. One lesion, selected for treatment with VYN201, had skin tissue biopsies taken prior to first application of VYN201 and after 8 weeks of treatment. Biopsies were analyzed to quantify the effect of VYN201 on specific biomarkers related to inflammation associated with vitiligo, melanocyte proliferation, and melanogenesis. Exploratory data from the 1.0% and 2.0% cohorts showed that VYN201 treatment demonstrated biological activity and a positive effect on certain key biomarkers relevant to vitiligo disease severity and progression. The magnitude of biomarker modulation was more pronounced in the 2.0% dose cohort than in the 1.0% dose cohort, indicative of an emerging dose-response.

Deal potentially worth over $50m in upfront and milestones plus mid-tier single digit royalties

DUNDEE, UK; 2^nd May, 2023 – Tay Therapeutics, focused on developing small molecules for oncology and severe inherited diseases, today announced that it has entered into an exclusive license agreement with VYNE Therapeutics Inc. (Nasdaq: VYNE), a US-based biotech focused on developing proprietary, innovative and differentiated therapies in immuno-inflammatory diseases, for its oral BET inhibitor, TAY-B2 (VYN202).

Tay Therapeutics out-licensed its topical pan-BET inhibitor to VYNE for £16m in upfront and milestone payments in 2021. The out-licensing of both of Tay Therapeutics’ BET inhibitor projects will bring potential milestone revenues of over $65m for the first indications along with tiered royalty payments of up to 10% of net annual sales.

TAY-B2 (VYN202) has demonstrated potent anti-inflammatory and anti-fibrotic effects in multiple

validated preclinical models, leading VYNE to exercise its option to progress TAY-B2 (VYN202) into a Phase I study to treat major immuno-inflammatory conditions with high unmet need. VYNE has initiated IND enabling studies and intends to file an IND in the U.S. by year-end.

Dr. Tim Sparey, Executive Chair of Tay Therapeutics, stated “We are delighted to announce this deal with VYNE Therapeutics. It follows the licensing of TAY-B1 (now known as VYN201), a topical BET inhibitor in 2021 and completes the out-licensing of our BET inhibitor projects to a partner with the development expertise in inflammatory and fibrotic diseases where there is high unmet need.”

Dr. Andrew Woodland, CEO of Tay Therapeutics, stated “The second deal with VYNE is the culmination of 2 years of discovery and development of BET inhibitors with differentiated selectivity and safety profiles. I’m delighted for the Tay team and consider VYNE ideally placed to continue developing and maximising the value of the BET inhibitor projects. This deal further validates Tay’s business model of growing organically using revenues to support development activities with ~£6m received in upfront and milestone payments from the VYNE collaboration to date.”

David Domzalski, President and CEO of VYNE stated “We are thrilled to be licensing the oral BET project from Tay. As a result of our productive partnership, we are poised to announce clinical results for the topical BET inhibitor that we in-licensed from Tay about two years ago and look forward to developing an oral BET inhibitor molecule in immuno-inflammatory conditions that we believe, based on pre-clinical results, is potentially best-in-class.”

 

About Tay Therapeutics

Tay Therapeutics is a biotech company that develops new small molecule therapeutics for oncology and severe inherited diseases.  Tay is a spin-out from the world leading University of Dundee’s School of Life Sciences and has laboratory facilities in Dundee, Scotland. With the out-licence of its BET inhibitor projects, Tay Therapeutics will now focus on developing a platform to discover and develop a new class of medicine that can cause the body to ignore premature stop codon (PTC) mutations leading to full-length, functional protein. By restoring functional proteins, our drugs seek to address the root cause of these diseases. Tay’s platform is called Tay-Enable.

Tay is supported by its seed investors o2h Ventures, Meltwind, Wren Capital, Scottish Enterprise and the University of Dundee.

About Bromodomain and Extra-Terminal Domain 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 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.

For more information, please visit www.taytherapeutics.com or contact Tim Sparey Ph.D (Executive Chair) tim@taytherapeutics.com (+44 (0) 7718864561).

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. VYNE’s unique and proprietary bromodomain & extra-terminal (BET) domain platform, licensed from Tay Therapeutics,  includes VYN201 (locally administered pan-BETi) and VYN202 (orally available selective-BETi).

For more information about VYNE Therapeutics Inc. or its product candidates, visit www.vynetherapeutics.com or contact Tyler Zeronda (CFO, VYNE) at 908-458-9106
Tyler.Zeronda@vynetx.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.

BRIDGEWATER, N.J., April 19, 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 new preclinical data showing the positive effect of its novel pan-BET inhibitor, VYN201, in a preclinical model of idiopathic pulmonary fibrosis (“IPF”).

“The data from this well-validated preclinical model of IPF clearly demonstrates VYN201’s potential to deliver a potent anti-inflammatory and anti-fibrotic response,” said David Domzalski, President and Chief Executive Officer of VYNE. “These data in IPF support our thesis that VYN201 has potential utility as a locally-administered therapy across a variety of immuno-inflammatory indications and further underscores the potential value of our InhiBET^TM BET inhibitor platform.”

Bleomycin-Induced Mouse Model

IPF is a chronic, life-threatening, fibrosing lung disease with few treatment options. Patients experience debilitating symptoms, including shortness of breath and difficulty performing daily activities. The current standard of care treatment options for IPF have been shown to have only a modest impact on slowing the progression of the disease and have been associated with significant side effects.

In this well-validated preclinical model for IPF, lung fibrosis was induced in mice using a single intratracheal dose of bleomycin. Fibrosis was left to develop for seven days, and thoracic tomography images were obtained to stage fibrotic development. Animals were assigned to six treatment groups: untreated and unstimulated control, placebo, and one of four doses of VYN201 (0.1, 0.2, 0.5, and 1.0 mg/ml) (N=6/group). Each treatment group was dosed intratracheally every other day for 14 days. Changes in blood oxygen saturation, Ashcroft scoring (a standardized numerical scale used to quantify the extent of lung fibrosis in histological samples), lung hydroxyproline (a tissue biomarker for fibrosis), and volumetric lung function were assessed.

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. 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.

BRIDGEWATER, N.J., Jan. 09, 2023 (GLOBE NEWSWIRE) — VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a biopharmaceutical company developing proprietary, innovative, and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced that the first vitiligo patient has been dosed in a Phase 1a/b clinical trial of VYN201. VYN201 is a locally administered, small molecule, pan-bromodomain and extra-terminal domain (BET) inhibitor that is being developed for the treatment of immuno-inflammatory diseases. The clinical trial is a first-in-human study designed to generate safety and pharmacokinetic data in healthy volunteers (Phase 1a) as well as provide early clinical proof-of-concept data in vitiligo patients (Phase 1b).

“Dosing the first vitiligo patient in our Phase 1a/b clinical trial represents a significant clinical milestone for VYNE and our novel InhiBET™ BET inhibitor platform,” said David Domzalski, President and Chief Executive Officer of VYNE. “I’m pleased with the progress our team has made to advance this critical program, and we look forward to reporting topline data for both the Phase 1a and Phase 1b portions of the study in the first half of 2023.”

In the Phase 1b portion, up to 30 patients with a clinical diagnosis of non-segmental vitiligo will receive VYN201 once daily in up to 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 pharmacodynamic biomarkers and photography.

BRIDGEWATER, N.J., Nov. 17, 2022 (GLOBE NEWSWIRE) — VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a biopharmaceutical company developing proprietary, innovative, and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced that the first subjects have been dosed in a Phase 1a/b clinical trial evaluating VYN201 for the treatment of vitiligo. VYN201 is a locally administered, small molecule, pan-bromodomain and extra-terminal domain (BET) inhibitor that is being developed for the treatment of immuno-inflammatory diseases. The clinical trial is a first-in-human study designed to generate safety and pharmacokinetic data in healthy volunteers as well as provide early clinical proof-of-concept data in vitiligo patients.

“We believe BET inhibitors have the potential to become a major new drug class for the treatment of vitiligo and other immuno-inflammatory diseases,” said David Domzalski, President and Chief Executive Officer of VYNE. “The initiation of this clinical trial for VYN201, the first of several planned programs for our InhiBETTM BET inhibitor platform, is a major milestone in our mission to improve the lives of patients suffering from immuno-inflammatory diseases. We look forward to topline data for both the Phase 1a and Phase 1b portions of the study, expected in the first half of 2023.”

The Phase 1 study will be conducted in U.S.-based clinical centers. The Phase 1a portion of the study will evaluate single ascending/multiple ascending doses in up to 30 healthy volunteers with VYN201 applied topically once daily for up to two weeks. The primary objective of this portion of the study is to characterize the preliminary safety and pharmacokinetics of VYN201 and to determine the safe starting dose for the Phase 1b portion of the study.

In the Phase 1b portion, up to 30 patients with a clinical diagnosis of non-segmental vitiligo will receive VYN201 once daily in up to three dose cohorts. Patients will receive treatment for an initial 8-week period based on currently available nonclinical safety data. The Company expects to extend the treatment period for up to an additional 12 weeks, subject to ongoing nonclinical safety assessments. The primary objective of the Phase 1b portion of the study will be to evaluate the safety and pharmacokinetics of VYN201. In addition, exploratory efficacy of VYN201 in non-segmental vitiligo patients will also be assessed. Clinical assessments will include safety, pharmacokinetics, local skin tolerance, efficacy, pharmacodynamic biomarkers and photography.

“By utilizing a soft-drug approach, topical VYN201 is designed to maximize target engagement in the skin and minimize systemic exposure. In an ex vivo human tissue model of vitiligo, VYN201 demonstrated a dose-dependent reduction in the loss of melanin pigment in the basal layers of skin and positively impacted key biomarkers that drive dyspigmentation in vitiligo. Further, VYN201 was found to upregulate the WNT signaling pathway which is an important mediator of both melanogenesis and melanocyte differentiation and is known to be dysregulated in patients with vitiligo,” said Dr. Iain Stuart, Chief Scientific Officer of VYNE. “Based upon these data, we believe VYN201 could be a promising and differentiated new therapy to address the unmet needs of patients with vitiligo.”

BRIDGEWATER, N.J., March 30, 2022 (GLOBE NEWSWIRE) — VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a biopharmaceutical company focused on developing proprietary, innovative, and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced positive preclinical data in a rheumatoid arthritis (“RA”) model from its VYN201 program. The data demonstrated that VYNE’s pan-BET inhibitor VYN201 used as an intra-articular injection resulted in significant inhibition of inflammation in a validated animal model of RA. The data supports the potential to develop VYN201 as a locally-administered intra-articular treatment for an autoimmune joint disease.

“The data from this preclinical model in rheumatoid arthritis is the latest to demonstrate VYN201’s potential to deliver a potent anti-inflammatory response and supports the potential broad therapeutic profile for VYN201 as a locally-administered pan-BET inhibitor,” said David Domzalski, Chief Executive Officer of VYNE. “We remain on track to initiate a first in-human clinical trial for VYN201 in the second half of this year.”

Anti-Collagen Antibody Induced Mouse Model of RA

RA is a chronic autoimmune and inflammatory disease with an average prevalence of 0.5–1.0% in the population worldwide. RA is characterized by inflammation of the synovial membrane, resulting in progressive cartilage damage and bone erosion. Symptoms of RA most commonly include pain, swelling, redness and stiffness in the affected joints, limiting the range of motion.

In this validated preclinical model for RA, inflammatory arthritis was induced in BALB/c mice by systemically injecting a mixture of four arthritogenic monoclonal antibodies against collagen II at day 1. In addition, the mice received a lipopolysaccharide injection systemically at day 4 to stimulate an acute systemic inflammatory response. Each treatment group (n=7 per group) was injected with either (i) an intra-articular dose of VYN201 vehicle, (ii) an intra-articular dose of VYN201, (iii) an intra-articular dose of dexamethasone (1mg/kg) or (iv) a systemic dose of dexamethasone (1mg/kg, via intraperitoneal injection). The intra-articular doses were administered on days 0, 3, 6 and 9 while the dexamethasone systemic injections were given daily beginning at day 0 through 11. For the VYN201 treatment groups, four doses of VYN201 were evaluated (at concentrations ranging from 0.01 to 10mg/kg). Each animal treated with the intra-articular injections received the injection in the ankle of one rear paw. The untreated rear paw was assessed to evaluate any potential anti-inflammatory systemic effect. Treatment response was evaluated based on an assessment of paw thickening or swelling (in millimeters) and arthritis scoring based on a five-point composite severity scale of redness, swelling of the ankles and wrists, and paw thickness. Scoring in this model ranges from 0 (normal) to 4 (extensive signs and symptoms of arthritis).

Key findings:

• Paw Thickening: VYN201 demonstrated marked inhibition of paw thickening at the 1 and 10mg/kg doses. At both doses, the inhibition of paw thickening was statistically significant in the treated paw relative to the untreated rear paw on day 12 (p<0.01).”
• For these VYN201 treatment groups, mean paw thickness at baseline (day 0) was 2.08 mm.
• For the 10mg/kg dose, the average paw thickness at day 12 was 3.48 mm in the untreated paw versus 2.17 mm in the treated paw, representing a 37.6% reduction.
• For the 1mg/kg dose, the average paw thickness at day 12 was 2.98 mm in the untreated paw versus 2.18 mm in the treated paw, representing a 26.8% reduction.
• Results with these two doses were numerically superior to intra-articular dexamethasone and consistent with the systemic dexamethasone treatment.
• Arthritis Score: Limbs treated with VYN201 at the 1 and 10mg/kg dose levels had an average arthritis score of 0.57 and 0.67, respectively, or near normal. The arthritis score was significantly lower in the treated paw at both doses relative to the non-treated paws on day 12 (p<0.05).
• At the 10mg/kg dose, the average arthritis score was 0.67 in the treated paw versus 3.33 in the untreated paw, representing a 79.9% reduction.
• At the 1mg/kg dose, the average arthritis score was 0.57 in the treated paw versus 2.43 in the untreated paw, representing a 76.5% reduction.
• Limbs treated with intra-articular dexamethasone received an average arthritis score of 1.3, indicating mild symptoms. These animals had signs of redness and swelling of the ankle/wrist or apparent redness and swelling limited to individual digits.

Locally Acting Anti-Inflammatory Effect:

Demonstrated improvement in signs and symptoms of joint inflammation were observed in the limbs of animals treated with VYN201, and no treatment effect was observed in untreated limbs, suggesting a locally acting anti-inflammatory effect of VYN201. In contrast, animals that received systemic dexamethasone experienced a treatment effect in all limbs.

Treatment tolerability was evaluated based on changes in body weight. Animals treated with systemic dexamethasone experienced continued weight loss throughout the study while all other treatment groups experienced improved body weights following recovery from the RA stimulant.

 

BRIDGEWATER, N.J., March 07, 2022 (GLOBE NEWSWIRE) — VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a biopharmaceutical company focused on developing proprietary, innovative, and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced positive preclinical data in an ex vivo skin model of vitiligo. In the preclinical model, pan-bromodomain and extra-terminal (“BET”) inhibitor VYN201 reduced the expression of key pro-inflammatory biomarkers relevant to the pathogenesis of vitiligo, and demonstrated marked reduction in melanocyte loss.

Vitiligo is a chronic autoimmune depigmenting disorder of the skin. There are currently no FDA approved drug therapies for the treatment of vitiligo. It is the most common depigmenting skin condition, with a prevalence estimated at 0.5-2% of the world population. Vitiligo is characterized by increased MMP-9 secretion and soluble E-cadherin2, resulting in a loss of pigment in the skin.

Reconstituted Human Epithelial Skin Model of Vitiligo

The objectives of this study were to evaluate the potential of VYN201 to (i) reduce Matrix Metalloproteinase-9 (“MMP-9”) secretion (reducing the secretion of MMP-9 allows for melanocyte stabilization and limits loss of melanocytes/depigmentation in vitiligo); (ii) reduce soluble adhesion molecule, E-cadherin (soluble E-cadherin is a biomarker of melanocyte loss due to degradation of matrix-bound E-cadherin by MMP-9); (iii) minimize the loss of melanocytes by assessing melanin pigment content and (iv) affect the expression of genes commonly associated with melanogenesis (melanin synthesis, melanosome maturation and transport).

In the study, reconstituted human epithelial skin cultures were stimulated with Tumor Necrosis Factor alpha (TNF-α) and Interferon gamma (IFN-ɣ) cytokines to induce a vitiligo phenotype (loss of melanin, increased MMP-9 secretion and increased soluble E-cadherin). The stimulated cultures were topically treated with vehicle, VYN201 at varying concentrations ranging from 0.001% – 1%, or an active control, topical ruxolitinib cream, 1.5%, at 3 mg/cm2. The topical treatments were applied to the skin cultures 24 hours prior to, and concomitantly with, cytokine induction.

Key findings from the study:

VYN201 produced a dose dependent reduction in MMP-9 and soluble E-cadherin:

Applications with VYN201 at each of the 0.1% and 1% concentrations resulted in statistically significant reductions in MMP-9 when compared to vehicle, with a 94.7% reduction in secreted MMP-9 for the VYN201 1% treatment (p<0.0001).

Applications with VYN201 at each of the 0.1% and 1% concentrations resulted in statistically significant reductions in the release of soluble E-cadherin relative to vehicle, with a 32.6% reduction in soluble E-cadherin for the VYN201 1% concentration (p<0.01).

VYN201 0.1% and 1% were both numerically superior to topical ruxolitinib cream, 1.5% in reducing the secretion of MMP-9 and soluble E-cadherin.

VYN201 at each of the 0.1% and 1% concentrations substantially reduced the loss of melanin pigment in the basal layers of skin:

Quantified melanin levels for VYN201 1% treated skin cultures were approximately 10-fold higher as compared to VYN201 vehicle treated skin cultures (p=0.03).

VYN201 positively impacted the expression of several genes implicated in the pathogenesis of vitiligo:

VYN201 0.1% and 1% resulted in a statistically significant reduction in the expression of inflammatory cytokines IL1-α and IL1-β relative to vehicle (VYN201 1%, p<0.0005). These cytokines are well recognized as significant contributors to inflammation in vitiligo and their over-expression correlates with disease progression.

VYN201 significantly upregulated the WNT signaling pathway at the 0.1% and 1% concentrations relative to vehicle, with a 10-fold increase observed at the 1% concentration (p<0.01). The WNT family of proteins and its signalling pathway is recognized as an important indicator of melanocyte regeneration.

“We are encouraged by the evolving therapeutic potential of our locally-administered pan-BET inhibitor, VYN201,” said David Domzalski, VYNE’s Chief Executive Officer. “This latest set of pre-clinical data in vitiligo reflects the potential broad utility for this molecule. We look forward to providing additional updates as we continue to advance this program toward in-human clinical trials later this year.”

In4Derm announces a £1.6m pre-Series A funding round to support the continued development and expansion of its pipeline of first-in-class anti-inflammatory and orphan indications therapeutics. In4Derm is a spin out from the world leading University of Dundee’s School of Life Sciences and has laboratory facilities in Dundee, Scotland.

Following spin out and a seed round in 2020, In4Derm entered an option and licensing arrangement for its topical and oral BET inhibitor (BETi) programmes with VYNE Therapeutics in early 2021. The deal brings potential payments including upfronts and milestones of over $80m along with royalties. In August 2021 VYNE announced the exercise of its option to license In4Derm’s topical BETi programme and its intention to begin clinical trials in 2022.

This pre-Series A financing will enable the continued development of In4Derm’s oral BETi programme and the expansion of its pipeline to include new assets targeting inflammation and orphan diseases.  Existing investors o2h Ventures, Meltwind, Wren Capital and Scottish Enterprise participated in the round and the University of Dundee invests for the first time.

Tim Sparey, CEO at In4Derm, said: “We’re delighted to announce this pre-Series A funding round. We’re pleased that the o2h Ventures team, Meltwind, Wren and Scottish Enterprise teams have continued to invest and we particularly welcome investment by the University of Dundee, in what is their first investment in a spin out. With our partnership with VYNE Therapeutics enabling the rapid development of our topical BETi, In4Derm is well placed to accelerate the development of and expand its pipeline to deliver increased value for its shareholders’.

Anne Muir, Head of IP and Commercialisation at the University of Dundee, said “We are delighted to be able to participate in this investment round which demonstrates our belief in the science and team as well as our commitment to regional impact. In4derm is another growing success story for the University and is testament to the excellence of our Life Sciences research.”

Scottish Enterprise Director of Growth Investments, Kerry Sharp said: “In4Derm is a fantastic example of an innovative Scottish early-stage business with global growth ambitions for its future. With Scottish Enterprise support, the drugs developed by In4Derm will help patients across the world and create jobs in Scotland while contributing to the continued growth of its vibrant life sciences sector.”

Sunil Shah, CEO at o2h Ventures, said: “The team at in4Derm have over-achieved on the milestones and goals that we agreed at the Seed round and given commercial validation with VYNE Therapeutics, we are very happy to lead the investment along with our co-investor syndicate of Meltwind, Wren, Scottish Enterprise and Dundee University. This round was oversubscribed by the existing investors which demonstrates the confidence that we have in this team and technology.”

BRIDGEWATER, N.J., Aug. 12, 2021 (GLOBE NEWSWIRE) — VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”) today announced that it has entered into an exclusive license agreement (the “License Agreement”) with In4Derm Limited (“In4Derm”), a spin-out of the University of Dundee’s School of Life Sciences focused on the discovery and development of proprietary Bromodomain and Extra-Terminal Domain inhibitors (“BET inhibitor” or “BETi”) for the treatment of immunology and oncology conditions. The University of Dundee is one of the foremost integrated university hospital and biotechnology research institutes in Europe.

“We are extremely excited to announce this potentially transformational transaction and to partner with In4Derm, a company devoted to developing small molecule drugs for anti-inflammatory and orphan indications,” said David Domzalski, President and CEO of VYNE. “This partnership provides us access to a novel BETi platform for both topical and oral treatments for immuno-inflammatory diseases of high unmet medical need. Initially we will advance a topical BETi program for the treatment of rare skin diseases into the clinic in 2022. We believe this collaboration will create numerous opportunities to drive value and look forward to providing further updates on our progress.”

Topical BETi program: VYN201 is a first-in-class topical pan-BD BET inhibitor that is designed to mitigate systemic drug exposure and will be developed for topical applications. VYNE intends to progress VYN201 in rare, neutrophilic, dermatological indications where there is significant unmet need due to a lack of indicated treatment options. This program is expected to enter the clinic in 2022.

Oral BETi program: VYNE expects to exercise its exclusive option with In4Derm to develop oral BET inhibitors following the selection of a lead candidate for the program. VYN202 is an orally-delivered, first-in-class BET inhibitor that is highly selective for Bromodomain 2 (“BD2”). By selectively inhibiting BD2, the Company believes VYN202 could have a more targeted anti-inflammatory effect with an improved benefit/risk profile and views VYN202 as having significant potential as a novel, oral treatment for major immuno-inflammatory indications. Upon final candidate selection and exercise of its option, the Company intends to commence an IND-enabling non-clinical safety program and enter the clinic next year.

There is substantial interest in BET inhibitors as therapeutic targets for a wide range of diseases. To date, much of the clinical research has been focused on oncology. The Company believes there is also compelling science to show that BET inhibition may play an important role in effectively treating immuno-inflammatory diseases.

In4Derm’s CEO Dr. Tim Sparey commented, “We are delighted to announce this strategic partnership with VYNE Therapeutics. Together, both companies share a vision to develop new therapeutics to treat high unmet needs in inflammation and rare diseases, where millions of patients suffer with no adequate treatment options. This partnership validates In4Derm’s ability to deliver high quality drug candidates in important markets and brings a partner with the necessary expertise to accelerate clinical development. We look forward to shared success with VYNE.”

The parties previously entered into an Evaluation and Option Agreement (the “Option Agreement”) pursuant to which In4Derm granted the Company an exclusive option to obtain exclusive worldwide rights to research, develop and commercialize products containing In4Derm’s BETi compounds, which are new chemical entities (NCEs), in both topical (the “Topical BETi Option”) and oral (the “Oral BETi Option”) treatments in all fields for any disease, disorder or condition in humans.

On August 6, 2021, the Company exercised the Topical BETi Option and the parties entered into a License Agreement granting the Company a worldwide, exclusive license that is sublicensable through multiple tiers to exploit certain of In4Derm’s BETi compounds identified to be suitable for topical administration in all fields. The Company paid a $1.0 million cash payment to In4Derm upon the execution of the Option Agreement and $0.5 million in connection with the exercise of the Topical BETi Option. Pursuant to the License Agreement, the Company has agreed to make cash payments to In4Derm upon the achievement of specified clinical development and regulatory approval milestones with respect to each licensed topical product in the U.S. of up to $15.75 million. In addition, the Company expects to exercise the Oral BETi Option following the selection of a lead candidate for the program. Upon exercise of the exclusive Oral BETi Option, the parties will sign a license agreement (the “Oral License Agreement”) and the Company will pay In4Derm a $4.0 million cash payment. The Oral License Agreement will include cash payments of up to $43.75 million payable to In4Derm upon the achievement of specified clinical development and regulatory approval milestones with respect to each licensed oral product in the U.S. The license agreements also provide for tiered royalty payments of up to 10% of net annual sales across licensed BETi products by the Company. In4Derm is entitled to additional milestone payments upon the achievement of regulatory approvals in certain jurisdictions outside the U.S.

In4Derm Ltd is an innovative drug discovery company developing the next generation of topical and oral therapies for widespread inflammatory conditions, including eczema and rheumatoid arthritis. It has attracted over £2 million in pre-company grants and investment and was recognised as Scotland’s top spinout opportunity for 2020 when it took top prize at the 2019 Converge Awards.

The company was founded by Dr Andrew Woodland and Dr Mark Bell, medicinal chemists at the University’s School of Life Sciences. They will be joined by biologist Dr Rangeetha Jayaprakash and led by experienced biotech entrepreneur Dr Tim Sparey as CEO. In4Derm plans to expand significantly as it moves towards its goal of making safe and effective anti-inflammatory drugs available for patients.

Steroid creams are frequently prescribed for skin diseases, but these can cause serious side effects as well as proving inadequate to bring diseases such as psoriasis and eczema under control. Patients may then be referred for more intensive treatment, which could include pills or injections. Many treatments are not suitable for children, who are also more likely to suffer from eczema than adults.

As a result, there is a significant unmet need for new treatments for these diseases, and In4Derm has identified a new approach that they hope to bring into clinical trials in the next few years.

“The issue is that steroid creams and available oral treatments are not suitable for long term treatment of eczema in adults and many children with eczema are undertreated due to safety concerns, which is distressing for them and their parents,” said Dr Woodland.

“We have discovered two promising prototype drugs that we will now refine before progressing through into clinical trials. One is a pill and the other is a non-steroid cream. The work we have carried out to this point suggests our cream could be superior both in terms of safety and efficacy than current creams, whilst the pill seems to be safer than existing systemic treatment.

“Across the world there are lots of drugs in development for eczema but we are the first to target this particular mechanism, which we believe will be safer and more effective, offering the benefits of steroids without the risk.”

In4Derm combines Dundee’s excellence in molecular science with its world-leading drug discovery expertise. The company will initially be funded through a variety of sources, including support from Scottish Enterprise’s High Growth Spin-out Programme (HGSP). Scottish Enterprise will continue to work with In4Derm on an ongoing basis via its High Growth Ventures team.

Abigail Lyons, HGSP programme manager at Scottish Enterprise, said, “It’s great to see the fantastic progress In4Derm has made over the 3 years that our High Growth Spin-out Programme has supported its commercial and technical development, including our recent investment of a £200,000 convertible loan. We look forward to seeing the company’s continued growth and to exploring how we can work together in the future.”

The HGSP supports the commercialisation of leading-edge technologies emerging from Scotland’s universities, research institutes and NHS Boards. It helps researchers to export their ideas and inventions from the lab to the global marketplace.

Dr Woodland was named Scotland’s top entrepreneurial academic last year when he received the top prize of £78,000 in the Converge Challenge category at the Converge 2019 Awards final.

Converge is Scotland’s largest company creation programme designed for staff, students and recent graduates across all Scottish universities. Since launching in 2011, the programme has trained hundreds of aspiring academic entrepreneurs and supported around 225 businesses, with a survival rate of above 80%.