VYNE Therapeutics Reports Positive Top-line Phase 1a MAD Data for VYN202, its Novel BD2-Selective BET Inhibitor
VYNE Therapeutics announced positive results from the multiple ascending dose (MAD) portion of its Phase 1a trial for VYN202, a novel BD2-selective BET inhibitor. The study demonstrated a favorable safety and tolerability profile with no serious adverse events or drug-related issues historically associated with earlier BET inhibitors.
Key findings include: favorable pharmacokinetics supporting once-daily dosing, dose-dependent exposure reaching steady state after 7 doses, and robust pharmacodynamic activity. The drug showed no interaction with methotrexate and demonstrated dose-dependent increases in target engagement biomarker HEXIM-11, with maximal effect at 0.5mg to 1.0 mg QD. VYN202 also inhibited multiple inflammatory biomarkers related to Th17 and Th1/myeloid activity.
VYNE Therapeutics ha annunciato risultati positivi dalla parte di dose ascendente multipla (MAD) del suo trial di Fase 1a per VYN202, un nuovo inibitore BET selettivo per BD2. Lo studio ha dimostrato un profilo di sicurezza e tollerabilità favorevole senza eventi avversi gravi o problemi legati al farmaco tradizionalmente associati agli inibitori BET precedenti.
I principali risultati includono: farmacocinetica favorevole che supporta la somministrazione una volta al giorno, esposizione dose-dipendente che raggiunge uno stato stazionario dopo 7 dosi, e robusta attività farmacodinamica. Il farmaco non ha mostrato interazioni con il metotrexato e ha evidenziato aumenti dose-dipendenti nel biomarcatore di impegno target HEXIM-11, con effetto massimo a 0.5mg fino a 1.0 mg QD. VYN202 ha inoltre inibito diversi biomarcatori infiammatori correlati all'attività di Th17 e Th1/myeloidi.
VYNE Therapeutics anunció resultados positivos de la parte de dosis ascendente múltiple (MAD) de su ensayo de Fase 1a para VYN202, un nuevo inhibidor BET selectivo de BD2. El estudio demostró un perfil de seguridad y tolerabilidad favorable sin eventos adversos graves o problemas relacionados con el fármaco asociados históricamente con inhibidores BET anteriores.
Los hallazgos clave incluyen: farmacocinética favorable que apoya la dosificación diaria, exposición dependiente de la dosis que alcanza un estado estable después de 7 dosis, y una robusta actividad farmacodinámica. El fármaco no mostró interacción con metotrexato y demostró aumentos dependientes de la dosis en el biomarcador de compromiso objetivo HEXIM-11, con efecto máximo a 0.5mg hasta 1.0 mg QD. VYN202 también inhibió múltiples biomarcadores inflamatorios relacionados con la actividad de Th17 y Th1/mieloides.
VYNE Therapeutics는 VYN202의 1상 임상시험의 다중 상승 용량(MAD) 부분에서 긍정적인 결과를 발표했습니다. 이 새로운 BD2 선택적 BET 억제제는 안전성 및 내약성 프로필이 좋다고 밝혔으며, 이전 BET 억제제와 역사적으로 연관된 심각한 부작용이나 약물 관련 문제가 없었습니다.
주요 findings는: 하루 한 번 투여를 지지하는 유리한 약리학적 동태, 7회 투여 후에 일정한 상태에 도달하는 용량 의존적 노출, 그리고 강력한 약리학적 활성을 포함합니다. 이 약물은 메토트렉세이트와의 상호작용이 없었고, 목표 약물 체계 지표인 HEXIM-11의 용량 의존적 증가를 나타내어, 0.5mg에서 1.0mg QD의 최대 효과를 보였습니다. VYN202는 Th17와 Th1/골수 활동과 관련된 여러 염증성 바이오마커도 억제하였습니다.
VYNE Therapeutics a annoncé des résultats positifs de la partie de dose croissante multiple (MAD) de son essai de phase 1a pour VYN202, un nouvel inhibiteur BET sélectif pour BD2. L'étude a démontré un profil de sécurité et de tolérance favorable sans événements indésirables graves ni problèmes liés au médicament historiquement associés à des inhibiteurs BET antérieurs.
Les résultats clés incluent : une pharmacocinétique favorable supportant une posologie une fois par jour, une exposition dépendante de la dose atteignant un état d'équilibre après 7 doses, et une activité pharmacodynamique robuste. Le médicament n'a montré aucune interaction avec le méthotrexate et a démontré des augmentations dépendantes de la dose du biomarqueur d'engagement cible HEXIM-11, avec un effet maximal à 0,5 mg à 1,0 mg QD. VYN202 a également inhibé plusieurs biomarqueurs inflammatoires liés à l'activité Th17 et Th1/myéloïde.
VYNE Therapeutics hat positive Ergebnisse aus dem Abschnitt zur mehrfachen Dosissteigerung (MAD) seiner Phase-1a-Studie für VYN202, einen neuartigen BD2-selektiven BET-Inhibitor, bekannt gegeben. Die Studie zeigte ein günstiges Sicherheits- und Verträglichkeitsprofil ohne schwerwiegende unerwünschte Ereignisse oder im historischen Zusammenhang mit früheren BET-Inhibitoren stehende medikamentenbezogene Probleme.
Wichtige Ergebnisse sind: günstige Pharmakokinetik, die eine einmal tägliche Dosierung unterstützt, eine dosisabhängige Exposition, die nach 7 Dosen den steady state erreicht, und eine robuste pharmakodynamische Aktivität. Das Medikament zeigte keine Interaktion mit Methotrexat und zeigte dosisabhängige Anstiege im Zielengagement-Biomarker HEXIM-11, mit maximaler Wirkung bei 0,5 mg bis 1,0 mg QD. VYN202 hemmte auch mehrere entzündliche Biomarker, die mit Th17- und Th1/myeloid-Aktivität in Zusammenhang stehen.
- Favorable safety profile with no serious adverse events
- Successful pharmacokinetics supporting once-daily dosing regimen
- No drug interaction with methotrexate, a common treatment for inflammatory conditions
- Demonstrated dose-dependent target engagement
- Effective inhibition of multiple inflammatory biomarkers
- None.
Insights
The Phase 1a MAD trial results for VYN202 represent a significant clinical milestone. The data reveals three important advantages: favorable safety profile, optimal pharmacokinetics and robust pharmacodynamic activity. Most notably, VYN202 avoided the typical safety concerns that have historically plagued BET inhibitors, such as thrombocytopenia - a critical differentiator that substantially improves its commercial viability.
The pharmacokinetic profile supporting once-daily dosing and steady-state achievement after 7 doses suggests excellent drug behavior in the body. The maintenance of blood levels within IC50 to IC90 thresholds indicates sustained therapeutic activity. The lack of interaction with methotrexate is particularly valuable for market positioning in immune-mediated disorders.
For investors unfamiliar with biotech: Think of VYN202 as a precision tool that's both safer and more efficient than previous versions. It's like upgrading from a sledgehammer to a surgical instrument - you get the desired effect with fewer unwanted consequences.
For a company with a market cap of just
Key value drivers include:
- Differentiated safety profile reducing development risk
- Once-daily dosing enhancing commercial potential
- Compatibility with methotrexate expanding market opportunity
- Promising results support VYN202’s potential as a novel, once-daily oral treatment for a broad range of immune-mediated disorders
- Consistent with Phase 1a SAD results, VYN202 demonstrated a favorable safety and tolerability profile with no drug-related adverse events historically associated with earlier generation, less selective BET inhibitors
- VYN202 demonstrated robust pharmacodynamic activity including evidence of target engagement and significant inhibition of inflammatory biomarkers relevant to several immune-mediated disorders in ex vivo stimulation assays
BRIDGEWATER, N.J., Dec. 23, 2024 (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 positive results from the multiple ascending dose (“MAD”) portion of its Phase 1a SAD/MAD trial of VYN202. The Phase 1a trial was a two-part, double-blind, placebo-controlled dose-escalation study in healthy volunteers consisting of single ascending dose (“SAD”) and MAD components to evaluate the safety, tolerability, pharmacokinetics (“PK”) and pharmacodynamics of VYN202.
Key Findings from the Top-line Phase 1a MAD Results for VYN202:
- VYN202 demonstrated a favorable safety and tolerability profile with no drug-related adverse events historically associated with earlier generation, less selective bromodomain and extra-terminal domain (“BET”) inhibitors, including thrombocytopenia, neutropenia or gastrointestinal toxicity findings
- No serious adverse events (AEs), discontinuations due to an AE or clinically meaningful treatment emergent adverse events (TEAEs). All TEAEs were considered mild or moderate in severity.
- No drug-related adverse events associated with laboratory results. There were no AEs of any severity grade relating to thrombocytopenia, which is a known dose-limiting toxicity associated with earlier generations of BET inhibitors.
- Favorable PK profile demonstrated for VYN202:
- Data supports once-daily dosing regimen.
- VYN202 demonstrated dose dependent exposure that reached steady-state after 7 once-daily doses.
- VYN202 blood levels were within key inhibitory thresholds of IC50 to IC90 against BD2 BRD4 for at least 24 hours at all doses.
- No drug-drug interaction was observed when VYN202 was co-administered with methotrexate, a treatment commonly used in the management of chronic immuno-inflammatory conditions.
- VYN202 demonstrated robust pharmacodynamic activity on target engagement and inflammatory biomarkers in ex vivo assays:
- VYN202 induced a dose-dependent increase in the target engagement biomarker HEXIM-11 with a maximal effect observed at 0.5mg to 1.0 mg QD.
- VYN202 inhibited the production of multiple inflammatory biomarkers related to Th17, Th1/myeloid and Th1/Tc dysregulated activity, consistent with preclinical models of VYN202.
“We are very excited by the PK, pharmacodynamic and safety data generated in this trial which not only support the further development of VYN202 but also give us increased confidence that VYN202 has the potential to become a novel treatment option for immune-mediated diseases,” said David Domzalski, President and Chief Executive Officer of VYNE. “VYN202 has been designed to address the adverse events that have been historically associated with early generation BET inhibitors. We believe the data from this Phase 1a SAD/MAD trial validates our drug design thesis for VYN202. Based on these positive results, we look forward to finalizing our clinical trial plans for VYN202 in patients over a longer duration of treatment.”
For more information on the Phase 1a trial results, please visit the investor section of VYNE’s website.
About the MAD Portion of the Phase 1a Trial
The MAD portion of the trial was designed to evaluate multiple ascending doses of VYN202 given to healthy volunteers for 14 days. Four study cohorts evaluated VYN202 dosed at 0.5mg QOD, 0.5mg QD, 1mg QD and 1mg QD in combination with methotrexate 7.5mg QWK. The 0.5mg QOD cohort was intended to approximate 0.25mg QD dosing and the methotrexate combination cohort evaluated potential drug-drug interactions with methotrexate, a treatment commonly used in the management of chronic inflammatory conditions.
The trial evaluated safety, tolerability, PK and exploratory pharmacodynamics of VYN202. Participant blood samples were stimulated ex-vivo to assess the pharmacodynamic impact of VYN202 on target engagement and inflammatory biomarkers.
About VYN202
VYN202 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 is common. VYN202 is structurally distinct from VYNE’s pan-BET inhibitor (VYN201) and covered by distinct Patent Cooperation Treaty and provisional composition of matter patent applications directed to new chemical entities and their uses.
About BET Inhibitors
BET proteins play a key role in regulating gene transcription via epigenetic interactions (“reading”). Recent research has identified a key role for these proteins in regulating activation of immune cells, including T and B cells, and subsequent inflammatory and fibrotic 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.
1 Lin, Xiaoyu et al. “HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues.” Molecular Cancer Therapeutics vol. 16,2 (2017): 388-396. doi:10.1158/1535-7163.MCT-16-0475.
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 Fraunces
LifeSci Advisors, LLC
917-355-2395
jfraunces@lifesciadvisors.com
Tyler Zeronda
VYNE Therapeutics Inc.
908-458-9106
Tyler.Zeronda@VYNEtx.com
Media Relations:
Mike Beyer
Sam Brown Inc.
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mikebeyer@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 VYNE’s product candidates, including VYN202, the potential benefits of VYNE’s product candidates, including VYN202, 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, 2023, 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.
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FAQ
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