Zymeworks Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating ZW171 in Advanced Mesothelin-Expressing Cancers
Zymeworks Inc. (Nasdaq: ZYME) has announced the dosing of the first patient in a Phase 1 clinical trial (NCT06523803) for ZW171, an investigational therapy targeting mesothelin (MSLN)-expressing cancers. The global study aims to evaluate the safety and tolerability of ZW171 in treating advanced ovarian cancer, non-small cell lung cancer (NSCLC), and other MSLN-expressing cancers.
The trial is designed as a two-part, open-label multi-center study, expected to enroll approximately 160 adult patients. Part 1 will focus on dose escalation in ovarian cancer and NSCLC patients, while Part 2 will involve dose expansion in three cohorts. The study will be conducted at sites in the United States, Europe, and the Asia-Pacific region.
Preclinical studies have shown ZW171's potential for potent, preferential killing of MSLN-overexpressing cells and stimulation of MSLN-dependent T cell activation, with potentially favorable tolerability.
Zymeworks Inc. (Nasdaq: ZYME) ha annunciato la somministrazione della prima dose a un paziente in uno studio clinico di Fase 1 (NCT06523803) per ZW171, una terapia sperimentale che mira a colpire i tumori esprimenti mesotelina (MSLN). Lo studio globale ha l'obiettivo di valutare la sicurezza e la tollerabilità di ZW171 nel trattamento di cancro ovarico avanzato, carcinoma polmonare non a piccole cellule (NSCLC) e altri tumori esprimenti MSLN.
Il trial è progettato come uno studio multicentrico a due fasi, aperto, che dovrebbe arruolare circa 160 pazienti adulti. La Parte 1 si concentrerà sull'aumento della dose nei pazienti con cancro ovarico e NSCLC, mentre la Parte 2 prevede un'espansione della dose in tre coorti. Lo studio sarà condotto in sedi negli Stati Uniti, in Europa e nella regione Asia-Pacifico.
Studi preclinici hanno mostrato il potenziale di ZW171 per l'uccisione potente e preferenziale delle cellule con sovraespressione di MSLN e la stimolazione dell'attivazione delle cellule T dipendenti da MSLN, con una tollerabilità potenzialmente favorevole.
Zymeworks Inc. (Nasdaq: ZYME) ha anunciado la dosificación del primer paciente en un ensayo clínico de Fase 1 (NCT06523803) para ZW171, una terapia en investigación dirigida a cánceres que expresan mesotelina (MSLN). El estudio global tiene como objetivo evaluar la seguridad y tolerabilidad de ZW171 en el tratamiento de cáncer de ovario avanzado, cáncer de pulmón no microcítico (NSCLC) y otros cánceres que expresan MSLN.
El ensayo está diseñado como un estudio multicéntrico de dos partes, a etiqueta abierta, que se espera que incluya aproximadamente 160 pacientes adultos. La Parte 1 se centrará en la escalada de dosis en pacientes con cáncer de ovario y NSCLC, mientras que la Parte 2 implicará una expansión de la dosis en tres cohortes. El estudio se llevará a cabo en sitios en los Estados Unidos, Europa y la región de Asia-Pacífico.
Los estudios preclínicos han demostrado el potencial de ZW171 para eliminar de manera potente y preferencial las células con sobreexpresión de MSLN y estimular la activación de células T dependientes de MSLN, con una tolerabilidad potencialmente favorable.
Zymeworks Inc. (Nasdaq: ZYME)는 ZW171에 대한 1상 임상 시험(NCT06523803)에서 첫 환자에게 약물을 투여했다고 발표했습니다. 이 연구는 메소텔린(MSLN) 발현 암을 타겟으로 하는 실험 치료제입니다. 글로벌 연구의 목적은 말기 난소암, 비소세포 폐암(NSCLC) 및 기타 MSLN 발현 암의 치료에서 ZW171의 안전성과 내약성을 평가하는 것입니다.
이 시험은 두 부분으로 구성된 다기관 개방형 연구로 설계되었으며, 약 160명의 성인 환자를 등록할 것으로 예상됩니다. 1부는 난소암 및 NSCLC 환자에서 용량 증량에 초점을 맞추고, 2부는 세 개의 코호트에서 용량 확대를 포함합니다. 이 연구는 미국, 유럽 및 아시아 태평양 지역의 여러 사이트에서 진행될 것입니다.
전임상 연구는 ZW171이 MSLN 과발현 세포에 대해 강력하고 선택적인 세포 사멸을 유도하고 MSLN 의존적 T 세포 활성화를 촉진할 수 있는 가능성을 보여주었으며, 잠재적으로 우수한 내약성을 지닐 수 있음을 보여주었습니다.
Zymeworks Inc. (Nasdaq: ZYME) a annoncé l'administration de la première dose à un patient dans un essai clinique de Phase 1 (NCT06523803) pour ZW171, une thérapie expérimentale visant à cibler les cancers exprimant la mésothéline (MSLN). L'étude mondiale vise à évaluer la sécurité et la tolérabilité de ZW171 dans le traitement du cancer de l'ovaire avancé, du cancer du poumon non à petites cellules (NSCLC) et d'autres cancers exprimant MSLN.
L'essai est conçu comme une étude multicentrique en deux parties, à étiquetage ouvert, et devrait inclure environ 160 patients adultes. La Partie 1 se concentrera sur l'escalade de doses chez les patients atteints de cancer de l'ovaire et de NSCLC, tandis que la Partie 2 impliquera une expansion des doses dans trois cohortes. L'étude sera menée dans des sites aux États-Unis, en Europe et dans la région Asie-Pacifique.
Les études précliniques ont montré le potentiel de ZW171 pour éliminer de manière puissante et préférentielle les cellules surexprimant MSLN et stimuler l'activation des cellules T dépendantes de MSLN, avec une tolérabilité potentiellement favorable.
Zymeworks Inc. (Nasdaq: ZYME) hat die Dosierung des ersten Patienten in einer Phase-1-Studie (NCT06523803) für ZW171 angekündigt, eine experimentelle Therapie zur Bekämpfung von mesothelin (MSLN)-exprimierenden Krebserkrankungen. Die globale Studie zielt darauf ab, die Sicherheit und Verträglichkeit von ZW171 bei der Behandlung von fortgeschrittenem Ovarialkarzinom, nicht-kleinzelligem Lungenkrebs (NSCLC) und anderen MSLN-exprimierenden Krebserkrankungen zu evaluieren.
Der Versuch ist als zweigeteilte, offene multizentrische Studie konzipiert, die voraussichtlich etwa 160 erwachsene Patienten einschließen wird. Teil 1 konzentriert sich auf die Dosissteigerung bei Patienten mit Ovarialkarzinom und NSCLC, während Teil 2 die Dosisunterteilung in drei Kohorten umfasst. Die Studie wird an Standorten in den Vereinigten Staaten, Europa und dem asiatisch-pazifischen Raum durchgeführt.
Präklinische Studien haben das Potenzial von ZW171 aufgezeigt, MSLN-überexprimierende Zellen wirksam und selektiv abzutöten und MSLN-abhängige T-Zell-Aktivierung zu stimulieren, mit potenziell vorteilhafter Verträglichkeit.
- First patient dosed in Phase 1 clinical trial for ZW171, targeting mesothelin-expressing cancers
- Preclinical studies show potent anti-tumor activity and favorable tolerability of ZW171
- ZW171 demonstrates greater anti-tumor activity compared to benchmark in MSLN-expressing tumor models
- Trial designed to rapidly generate clinical data on differentiated product profile
- None.
Insights
The initiation of the Phase 1 clinical trial for ZW171 marks a significant milestone for Zymeworks in their oncology pipeline. This novel T cell engager targeting mesothelin (MSLN) shows promise in addressing ovarian cancer and non-small cell lung cancer (NSCLC), two areas with high unmet medical needs.
Key points to consider:
- ZW171's preclinical data demonstrated potent and preferential killing of MSLN-overexpressing cells, potentially reducing off-target toxicity.
- The trial's design, encompassing both dose escalation and expansion phases, allows for comprehensive safety and efficacy evaluation.
- With
84% of ovarian cancers and36% of NSCLC expressing MSLN, ZW171 could have a significant market potential if successful. - The global nature of the trial (U.S., Europe, Asia-Pacific) may accelerate enrollment and provide diverse patient data.
While promising, investors should note that this is an early-stage trial and success in preclinical studies doesn't guarantee clinical efficacy or regulatory approval. The trial's progress and interim results will be important in assessing ZW171's potential impact on Zymeworks' future.
The initiation of the ZW171 Phase 1 trial is a positive development for Zymeworks, potentially expanding its clinical pipeline and long-term value proposition. Key financial implications include:
- Resource Allocation: Running a global Phase 1 trial with 160 patients will require significant financial investment, impacting near-term cash burn.
- Market Opportunity: Targeting MSLN-expressing cancers, particularly ovarian and NSCLC, represents a substantial market. Success could lead to significant revenue potential.
- Diversification: ZW171 adds to Zymeworks' pipeline, reducing reliance on any single asset and potentially de-risking the company's overall portfolio.
- Partnerships: Positive early data could attract potential partnerships or licensing deals, providing non-dilutive funding.
With a market cap of
- Global Phase 1 clinical trial will evaluate the safety and tolerability of ZW171 in treatment of ovarian cancer, non-small cell lung cancer (NSCLC), and other mesothelin (MSLN) expressing cancers
VANCOUVER, British Columbia, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, today announced that the first patient has been dosed in the first-in-human Phase 1 trial (NCT06523803) to evaluate the safety and tolerability of the investigational therapy ZW171 in the treatment of advanced or metastatic ovarian cancer, NSCLC, and other MSLN-expressing cancers.
MSLN has strong expression in a broad number of tumor indications, including ovarian cancer (~
Data presented at the American Association for Cancer Research Annual Meeting in 2023 demonstrated that ZW171 exhibits greater anti-tumor activity compared to benchmark in MSLN-expressing tumor models and is well tolerated in cynomolgus monkeys up to 30 mg/kg2.
“We are very pleased to have initiated the clinical evaluation of ZW171 for the treatment of patients with ovarian cancer and NSCLC, where it has the potential to be a highly effective therapy with favorable tolerability based on our preclinical research results,” said Jeff Smith, M.D., FRCP, Executive Vice President and Chief Medical Officer at Zymeworks. “Initiation of this trial marks a significant step forward in our effort to bring a potential new treatment to people living with difficult to treat cancers and highlights our goal to advance two therapeutic candidates, ZW171 and ZW191, into clinical studies in 2024.”
The Phase 1 study is a two-part, open-label multi-center study that is expected to enroll approximately 160 adult patients with advanced MSLN-expressing cancers. Part 1 of the study will evaluate the safety and tolerability of ZW171 and involve dose escalation in patients with advanced ovarian and NSCLC, with secondary endpoints assessing pharmacokinetics and confirmed objective response rate. Part 2 of the study will involve dose expansion in three cohorts (ovarian cancer, NSCLC, and a basket cohort enrolling patients with any MSLN-expression) and will evaluate the anti-tumor activity of ZW171, with primary endpoints focused on safety and tolerability and secondary endpoints assessing progression-free survival, duration of response rates, and overall survival. The Company expects to conduct the Phase 1 study at investigator sites in the United States, Europe, and the Asia-Pacific region.
“We are also encouraged by the levels of interest in ZW171, which represents a promising and differentiated approach in the treatment of advanced mesothelin-expressing cancers,” Dr. Smith added, noting, “Our trial is designed to rapidly generate clinical data on our differentiated product profile relative to other mesothelin-expressing therapeutics in clinical development.”
About ZW171
ZW171 is a bispecific antibody designed to enable T cell-mediated tumor cell killing through simultaneous binding to the extracellular domain of MSLN protein on tumor cells and the engagement of CD3 on T cells. Moderate to high membranous MSLN expression is frequent in ovarian cancer, non-small cell lung cancer, mesothelioma and other cancers3. Preliminary evidence of anti-tumor activity with engineered T-cell therapy supports utility of T-cell targeted therapies in treatment of MSLN-expressing solid tumors4. ZW171’s unique 2+1 format and incorporation of a novel low-affinity anti-CD3 binder aims to improve the therapeutic window in patients by limiting on-target, off-tumor effects and cytokine release syndrome (CRS) while maintaining potent anti-tumor activity against MSLN-expressing cancers5. By selectively binding to tumors and sparing normal tissues, ZW171 is designed to improve both tolerability and anti-tumor activity against MSLN-expressing cancers. Engineered using our Azymetric™ and EFECT™2 technologies, ZW171 demonstrates enhanced anti-tumor activity and safety in preclinical models, inducing potent, preferential killing of MSLN-overexpressing cells while mitigating the risk of on-target, off-tumor activity, peripheral T cell activation, and CRS.
About Zymeworks Inc.
Zymeworks is a global clinical-stage biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat cancers and other diseases. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with HER2-expressing cancers. A Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for zanidatamab as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) has been accepted and granted Priority Review. A BLA has also been accepted for review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S. and China. Zymeworks is rapidly advancing a robust pipeline of wholly-owned product candidates, leveraging its expertise in both antibody-drug conjugates and multispecific antibody therapeutics targeting novel pathways in areas of significant unmet medical need. Phase 1 studies for ZW171 and ZW191 are now actively recruiting. In addition to Zymeworks’ pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X.
Forward Looking Statements
This press release includes “forward-looking statements” or information within the meaning of the applicable securities legislation, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this press release include, but are not limited to, statements that relate to the timing and status of ongoing and future studies and the release of data; expectations regarding future regulatory filings and approvals and the timing thereof; the timing of and results of interactions with regulators; anticipated regulatory submissions and the timing thereof; Zymeworks’ preclinical pipeline; the anticipated benefits of the collaboration agreements with Jazz and BeiGene; the commercial potential of technology platforms and product candidates; Zymeworks’ clinical development of its product candidates and enrollment in its clinical trials; the potential addressable market of zanidatamab; potential safety profile and therapeutic effects of zanidatamab and Zymeworks’ other product candidates; the ability to advance product candidates into later stages of development; and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “anticipate”, “potential”, “will”, “continues”, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Zymeworks’ current expectations and various assumptions. Zymeworks believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Zymeworks may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various factors, including, without limitation: future clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; any of Zymeworks’ or its partners’ product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; the impact of pandemics and other health crises on Zymeworks’ business, research and clinical development plans and timelines and results of operations, including impact on its clinical trial sites, collaborators, and contractors who act for or on Zymeworks’ behalf; the impact of new or changing laws and regulations; market conditions; inability to maintain or enter into new partnerships or strategic collaborations; and the factors described under “Risk Factors” in Zymeworks’ quarterly and annual reports filed with the Securities and Exchange Commission (copies of which may be obtained at www.sec.gov and www.sedar.com).
Although Zymeworks believes that such forward-looking statements are reasonable, there can be no assurance they will prove to be correct. Investors should not place undue reliance on forward-looking statements. The above assumptions, risks and uncertainties are not exhaustive. Forward-looking statements are made as of the date hereof and, except as may be required by law, Zymeworks undertakes no obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances, or to reflect the occurrences of unanticipated events.
Contacts:
Investor Inquiries:
Shrinal Inamdar
Director, Investor Relations
(604) 678-1388
ir@zymeworks.com
Media Inquiries:
Diana Papove
Senior Director, Corporate Communications
(604) 678-1388
media@zymeworks.com
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1 Weidemann, S. et al. Biomedicines 2021, Apr 7;9(4):397
2 Afacan N, et al. Presented at: AACR. 2023 (abstr #2942)
3 Chang K, Pastan I, Proc Natl Acad Sci U S A. 1996;93(1):136-40
4 Hassan R, et al. Nat Med. 2023;29:2099-2109
5 Wang L, et al., Cancer Immunol Res. 2019; 7(12): 2013–2024
FAQ
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