Ventyx Biosciences Announces Presentation of Data from the Phase 2 Trial of Allosteric TYK2 Inhibitor VTX958 in Crohn’s Disease at ECCO 2025
Ventyx Biosciences (VTYX) announced Phase 2 trial results for VTX958, its TYK2 inhibitor for Crohn's disease. While the trial did not meet its primary endpoint of change in Crohn's Disease Activity Index (CDAI), likely due to high placebo response, it demonstrated significant endoscopic improvements. The study showed dose-dependent endoscopic response rates of 24.3% for 225mg and 32.4% for 300mg doses, compared to 5.7% for placebo at Week 12.
The trial involved 109 subjects randomized across placebo and two VTX958 dosage groups (225mg and 300mg BID) for a 12-week induction period, followed by a 40-week maintenance phase. Notable results included significant reductions in SES-CD scores for both dosage groups compared to placebo, and improved clinical-biomarker response rates (43.2% for 300mg vs 14.3% for placebo). The company is analyzing full 52-week data to inform future development strategy and partnership opportunities.
Ventyx Biosciences (VTYX) ha annunciato i risultati della fase 2 della sperimentazione per VTX958, il suo inibitore TYK2 per la malattia di Crohn. Sebbene la sperimentazione non abbia raggiunto il suo obiettivo primario di cambiamento nell'Indice di Attività della Malattia di Crohn (CDAI), probabilmente a causa dell'alto tasso di risposta al placebo, ha dimostrato miglioramenti endoscopici significativi. Lo studio ha mostrato tassi di risposta endoscopica dipendenti dalla dose del 24,3% per la dose di 225mg e del 32,4% per quella di 300mg, rispetto al 5,7% per il placebo alla Settimana 12.
La sperimentazione ha coinvolto 109 soggetti randomizzati tra placebo e due gruppi di dosaggio di VTX958 (225mg e 300mg BID) per un periodo di induzione di 12 settimane, seguito da una fase di mantenimento di 40 settimane. I risultati notevoli includevano riduzioni significative nei punteggi SES-CD per entrambi i gruppi di dosaggio rispetto al placebo e tassi di risposta clinico-biomarker migliorati (43,2% per 300mg contro 14,3% per il placebo). L'azienda sta analizzando i dati completi delle 52 settimane per informare la strategia di sviluppo futura e le opportunità di partenariato.
Ventyx Biosciences (VTYX) anunció los resultados del ensayo de fase 2 para VTX958, su inhibidor de TYK2 para la enfermedad de Crohn. Aunque el ensayo no alcanzó su objetivo primario de cambio en el Índice de Actividad de la Enfermedad de Crohn (CDAI), probablemente debido a una alta respuesta al placebo, demostró mejoras endoscópicas significativas. El estudio mostró tasas de respuesta endoscópica dependientes de la dosis del 24.3% para la dosis de 225mg y del 32.4% para la de 300mg, en comparación con el 5.7% para el placebo a la Semana 12.
El ensayo involucró a 109 sujetos randomizados entre placebo y dos grupos de dosificación de VTX958 (225mg y 300mg BID) durante un período de inducción de 12 semanas, seguido de una fase de mantenimiento de 40 semanas. Los resultados notables incluyeron reducciones significativas en los puntajes SES-CD para ambos grupos de dosificación en comparación con el placebo, y tasas de respuesta clínico-biomarcador mejoradas (43.2% para 300mg frente al 14.3% para el placebo). La empresa está analizando los datos completos de 52 semanas para informar la estrategia de desarrollo futura y las oportunidades de asociación.
벤티엑스 바이오사이언스(VTYX)는 크론병에 대한 TYK2 억제제 VTX958의 2상 시험 결과를 발표했습니다. 이 시험은 크론병 활동 지수(CDAI) 변화라는 주요 목표를 달성하지 못했지만, 이는 높은 플라시보 반응 때문일 가능성이 큽니다. 그러나 상당한 내시경적 개선을 보였습니다. 연구 결과 용량 의존적인 내시경적 반응률이 225mg 용량에서 24.3%, 300mg 용량에서 32.4%로 나타났으며, 12주 차 플라시보의 반응률은 5.7%였습니다.
이 시험은 109명의 피험자가 플라시보 및 두 개의 VTX958 용량 그룹(225mg 및 300mg BID)으로 무작위 배정되어 12주 유도 기간을 거친 후 40주 유지 기간을 포함했습니다. 주목할 만한 결과로는 플라시보와 비교하여 두 용량 그룹 모두에서 SES-CD 점수가 유의미하게 감소했으며, 임상 바이오마커 반응률도 개선되었습니다(300mg의 43.2% 대 플라시보의 14.3%). 회사는 향후 개발 전략 및 파트너십 기회를 알리기 위해 52주 전체 데이터를 분석하고 있습니다.
Ventyx Biosciences (VTYX) a annoncé les résultats de l'essai de phase 2 pour VTX958, son inhibiteur de TYK2 pour la maladie de Crohn. Bien que l'essai n'ait pas atteint son objectif principal de changement de l'Indice d'Activité de la Maladie de Crohn (CDAI), probablement en raison d'une forte réponse au placebo, il a démontré des améliorations endoscopiques significatives. L'étude a montré des taux de réponse endoscopique dépendants de la dose de 24,3% pour la dose de 225mg et de 32,4% pour la dose de 300mg, contre 5,7% pour le placebo à la Semaine 12.
L'essai a impliqué 109 sujets randomisés entre placebo et deux groupes de dosage de VTX958 (225mg et 300mg BID) pendant une période d'induction de 12 semaines, suivie d'une phase de maintien de 40 semaines. Les résultats notables comprenaient des réductions significatives des scores SES-CD pour les deux groupes de dosage par rapport au placebo, et des taux de réponse clinique-biomarqueur améliorés (43,2% pour 300mg contre 14,3% pour le placebo). L'entreprise analyse les données complètes sur 52 semaines pour informer la stratégie de développement future et les opportunités de partenariat.
Ventyx Biosciences (VTYX) hat die Ergebnisse der Phase-2-Studie zu VTX958, seinem TYK2-Inhibitor für Morbus Crohn, bekannt gegeben. Obwohl die Studie ihr primäres Ziel, die Veränderung des Crohn's Disease Activity Index (CDAI), nicht erreicht hat, wahrscheinlich aufgrund einer hohen Placeboantwort, zeigte sie signifikante endoskopische Verbesserungen. Die Studie ergab dosisabhängige endoskopische Ansprechraten von 24,3% für die Dosis von 225mg und 32,4% für die Dosis von 300mg, verglichen mit 5,7% für das Placebo in Woche 12.
Die Studie umfasste 109 Probanden, die randomisiert auf Placebo und zwei VTX958-Dosierungsgruppen (225mg und 300mg BID) über einen 12-wöchigen Induktionszeitraum verteilt wurden, gefolgt von einer 40-wöchigen Erhaltungsphase. Bemerkenswerte Ergebnisse umfassten signifikante Reduktionen der SES-CD-Werte für beide Dosierungsgruppen im Vergleich zum Placebo und verbesserte klinisch-biomarker Ansprechraten (43,2% für 300mg vs. 14,3% für Placebo). Das Unternehmen analysiert die vollständigen 52-Wochen-Daten, um zukünftige Entwicklungsstrategien und Partnerschaftsmöglichkeiten zu informieren.
- Significant endoscopic response rates: 24.3% (225mg) and 32.4% (300mg) vs 5.7% placebo
- Strong clinical-biomarker response: 43.2% (300mg) vs 14.3% placebo
- Favorable safety profile reported
- Demonstrated dose-dependent efficacy in endoscopic measures
- Failed to meet primary endpoint (CDAI score change)
- Higher than expected placebo response affected trial results
Insights
The Phase 2 results for VTX958 reveal a nuanced efficacy profile that warrants careful analysis. While missing the primary CDAI endpoint, the trial demonstrated compelling evidence of biological activity through two critical measures: endoscopic improvement and inflammatory biomarker reduction.
The endoscopic response rate of 32.4% at the 300mg dose is particularly noteworthy, as endoscopic healing is increasingly recognized as a more reliable indicator of disease modification than symptomatic measures. Endoscopic improvement represents actual mucosal healing, which correlates better with long-term outcomes than patient-reported symptoms.
The biomarker data adds another layer of validation, with significant reductions in both C-reactive protein and fecal calprotectin. These objective measures of inflammation support the mechanism of action and suggest real biological impact. The 43.2% clinical-biomarker response rate in the 300mg group indicates meaningful disease activity reduction.
The safety profile appears favorable, which is important for an oral therapy targeting the TYK2 pathway. This could position VTX958 as an attractive option for earlier-line treatment, where patients and physicians often prefer oral medications before escalating to biologics.
The higher-than-expected placebo response in CDAI scores is a known challenge in Crohn's disease trials. Historical precedent suggests that longer treatment duration often reveals greater separation from placebo, particularly in symptomatic measures. This phenomenon, combined with the robust endoscopic and biomarker data, suggests potential for stronger efficacy signals in extended studies.
For Ventyx, these results present both opportunities and challenges. The endoscopic and biomarker data could attract partnership interest, particularly given the substantial market for oral Crohn's disease therapies. However, additional studies may be needed to optimize trial design and demonstrate more definitive symptomatic benefits.
Poster highlights robust, dose-dependent endoscopic response with VTX958 and reductions in key inflammatory markers
Full analysis of Phase 2 results, including data from the 52-week treat-through LTE phase, is expected to inform development strategy and partnership opportunities for VTX958
SAN DIEGO, Feb. 18, 2025 (GLOBE NEWSWIRE) -- Ventyx Biosciences, Inc. (Nasdaq: VTYX) (“Ventyx”, “Company”), a clinical-stage biopharmaceutical company focused on developing innovative oral therapies for patients with autoimmune, inflammatory, and neurodegenerative diseases, today announced that data from the Phase 2 trial of its TYK2 inhibitor VTX958 in Crohn’s disease will be presented during the 20th Congress of the European Crohn’s and Colitis Organisation (ECCO) being held in Berlin, Germany from February 19-22, 2025.
“The Phase 2 data for VTX958 in Crohn’s disease represent an important milestone for TYK2 inhibition in inflammatory bowel disease,” said Raju Mohan, PhD, Founder and Chief Executive Officer. “This trial did not meet the primary endpoint of change from baseline in the Crohn’s disease activity index, or CDAI (symptomatic outcome), likely due to a higher-than-expected placebo response. We did, however, observe a robust, dose-dependent endoscopic response, which was also associated with improvements in key inflammatory markers, including C-reactive protein and fecal calprotectin. Based on precedents from other Phase 3 trials in Crohn’s disease, we believe that VTX958 has the potential to show greater placebo-adjusted clinical remission rates with longer duration of therapy, including potential for reduced placebo response on symptomatic measures. These results give us confidence that TYK2 inhibition via VTX958 has the potential to offer a safe and effective treatment for Crohn’s disease, an indication with high unmet need for oral therapies. We also see potential for development as an advanced combination therapy with other oral and biologic agents.”
“There remains great need in Crohn’s disease for new safe and effective oral therapies,” commented Silvio Danese, MD, PhD, Professor of Gastroenterology at Vita-Salute San Raffaele University, Milan, Italy. “These Phase 2 data suggest that VTX958 has the potential for disease-modifying benefit in Crohn’s disease, including strong effects on endoscopic response, an outcome measure increasingly preferred as a primary endpoint in Phase 2 trials based on its stringency and objectivity. The totality of the Phase 2 data for VTX958, including a favorable safety profile, warrant further investigation in future clinical trials for Crohn’s disease.”
Poster and Abstract Information:
| Title: | Efficacy and safety of an oral tyrosine kinase 2 inhibitor VTX958 in moderately to severely active Crohn’s disease: a randomised, double-blind, placebo-controlled, phase 2 trial |
| Poster # | P1001 |
| Session: | February 21, 2025, 12:40-1:40 PM CET; Poster Exhibition, Hall 2.2 |
| Abstract: | Journal of Crohn's and Colitis, https://doi.org/10.1093/ecco-jcc/jjae190.1175 |
Phase 2 Trial Overview
The randomized, double-blind, placebo-controlled Phase 2 trial (NCT05688852) was designed to evaluate the safety and efficacy of VTX958 in adults with moderately-to-severely-active Crohn’s disease. One hundred and nine (109) subjects were randomized 1:1:1 to placebo, VTX958 225 mg BID, or VTX958 300 mg BID for a 12-week induction treatment period, followed by a 40-week double-blind maintenance period. Baseline characteristics were comparable across treatment groups. The primary endpoint was the change in the Crohn’s Disease Activity Index (CDAI) from baseline to Week 12. Secondary endpoints included additional symptomatic and endoscopic (as measured by the simple endoscopic score for Crohn’s disease, or SES-CD) measures, as well as inflammatory biomarkers.
While the primary endpoint was not met, likely due to a higher-than-expected placebo response, improvements in endoscopic results were observed. These improvements were associated with reductions in key inflammatory biomarkers. VTX958 was well tolerated in this Phase 2 trial.
- Change in CDAI Score (Primary): Reductions in CDAI from baseline were observed with VTX958 at Week 12 (-134.1 points for VTX958 225 mg; -113.6 points for VTX958 300 mg); however, these results did not reach statistical significance, likely due to a higher-than-expected response in the placebo group
(-104.3 points; p>0.05).
- Change in SES-CD Score: Reductions from baseline in the SES-CD score were observed with VTX958 225 mg (-3.5 points, p<0.0001) and VTX958 300 mg (-2.7 points, p=0.0005) compared to placebo (+2.1 points).
- Endoscopic Response: A greater proportion of participants on VTX958 achieved endoscopic response, defined as a ≥
50% reduction from baseline in the SES-CD score, compared to placebo. Endoscopic response rates were robust and dose-dependent, with24.3% of participants on VTX958 225 mg (p=0.0263) and32.4% on VTX958 300 mg (p=0.0066) achieving endoscopic response at Week 12, compared to5.7% of participants on placebo.
- Combined Endoscopic Response and Clinical Remission: A greater proportion of participants on VTX958 achieved both clinical remission (CDAI score <150) and endoscopic response compared to placebo (
18.9% VTX958 300 mg vs.2.9% placebo; p=0.0408), indicating that participants with an endoscopic response also achieved improvement in their clinical signs and symptoms.
- Combined Clinical-Biomarker Response: A greater proportion of participants on VTX958 achieved a clinical-biomarker response (
43.2% VTX958 300 mg vs.14.3% placebo; p=0.0105). Clinical-biomarker response was defined as a ≥100 point reduction in CDAI score or CDAI score <150 combined with a ≥50% reduction from baseline in C-reactive protein and/or fecal calprotectin.
Based on these results, and recognizing the unmet need and opportunity for a safe and effective oral TYK2 inhibitor as early-line therapy in Crohn’s disease, we are continuing the analysis of the Phase 2 data including data from the 52-week treat-through long-term extension phase. Full analysis of the Phase 2 data is expected to inform future development strategy and partnership opportunities for VTX958 in Crohn's disease.
About Ventyx Biosciences
Ventyx Biosciences is a clinical-stage biopharmaceutical company developing innovative oral therapies for patients with autoimmune, inflammatory, and neurodegenerative diseases. Our expertise in medicinal chemistry, structural biology, and immunology enables the discovery of differentiated oral small molecule therapeutics for conditions with high unmet medical need, and our extensive experience in clinical development allows the rapid progression of these drugs through clinical trials. Our lead portfolio of NLRP3 inhibitors includes VTX2735, a peripherally restricted NLRP3 inhibitor in Phase 2 development for recurrent pericarditis, and VTX3232, a CNS-penetrant NLRP3 inhibitor in Phase 2 development for neurodegenerative and cardiometabolic diseases. Our inflammatory bowel disease portfolio includes tamuzimod (VTX002), an S1P1R modulator, and VTX958, a TYK2 inhibitor, both of which have completed Phase 2 clinical trials. For more information on Ventyx, please visit our website at https://ventyxbio.com.
Forward-Looking Statements
Ventyx cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Ventyx’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the potential for VTX958 to be an active agent for Crohn’s disease and the potential to be evaluated further as a monotherapy or in combination regimen; the continued analysis of the discordance between symptomatic and endoscopic response data, and any ability to draw conclusions therefrom; management’s plans with respect to the commitment of internal resources toward further analysis, or development, including future studies partnerships or other sources of non-dilutive financing, for VTX958 in Crohn’s disease; and a change in study design for VTX958 in Crohn’s would yield greater placebo-adjusted clinical remission rates or a reduction in placebo response on symptomatic measures.
The inclusion of forward-looking statements should not be regarded as a representation by Ventyx that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Ventyx’s business, including, without limitation: whether any insights can be derived from the analysis of the discordance between symptomatic and endoscopic response data in the Phase 2 trial; potential delays in the commencement, enrollment and completion of clinical trials; Ventyx’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; disruptions in the supply chain, including raw materials needed for manufacturing and animals used in research, delays in site activations and enrollment of clinical trials; the results of preclinical studies and clinical trials; early clinical trials not necessarily being predictive of future results; interim results not necessarily being predictive of final results; the potential of one or more outcomes to materially change as a trial continues and more patient data become available and following more comprehensive audit and verification procedures; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of Ventyx’s product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; Ventyx’s ability to obtain and maintain intellectual property protection for its product candidates; the use of capital resources by Ventyx sooner than expected; and other risks described in Ventyx’s prior press releases and Ventyx’s filings with the Securities and Exchange Commission (SEC), including in Part II, Item 1A (Risk Factors) of Ventyx’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed on or about November 7, 2024, and Ventyx’s subsequent filings with the SEC.
You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Ventyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Investor Relations Contact:
Joyce Allaire
Managing Director
LifeSci Advisors
IR@ventyxbio.com
FAQ
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