Zymeworks Announces FDA Clearance of Investigational New Drug Application for ZW191, a Novel Folate Receptor-⍺ Targeted Topoisomerase I Inhibitor Antibody-Drug Conjugate
Zymeworks Inc. (Nasdaq: ZYME) announced FDA clearance of its Investigational New Drug (IND) application for ZW191, a novel folate receptor-⍺ (FR⍺) targeted topoisomerase I inhibitor antibody-drug conjugate (ADC). ZW191 targets FR⍺-expressing tumors, including ovarian, gynecological cancers, and non-small cell lung cancer (NSCLC). The drug incorporates a unique combination of antibody-linker stability and payload potency, with strong bystander activity.
Key features of ZW191 include:
- A drug-antibody ratio of eight for balanced tolerability and efficacy
- In-house generated FR⍺ monoclonal antibody for enhanced internalization
- Ability to target high, mid, and low levels of FR⍺ expression
- Robust anti-tumor activity and strong safety profile in preclinical models
Zymeworks Inc. (Nasdaq: ZYME) ha annunciato l'approvazione da parte della FDA della sua domanda per il Farmaco Nuovo Investigativo (IND) per ZW191, un nuovo coniugato anticorpo-farmaco (ADC) mirato al recettore della folato-⍺ (FR⍺) con azione inibitoria sulla topoisomerasi I. ZW191 colpisce i tumori che esprimono FR⍺, inclusi i tumori ovarici, i tumori ginecologici e il carcinoma polmonare non a piccole cellule (NSCLC). Il farmaco utilizza una combinazione unica di stabilità dell'anticorpo-linker e potenza del payload, con una forte attività di bystander.
Le caratteristiche principali di ZW191 includono:
- Un rapporto farmaco-anticorpo di otto per un bilanciamento tra tollerabilità ed efficacia
- Anticorpo monoclonale FR⍺ generato internamente per una migliore internalizzazione
- Capacità di colpire i livelli alti, medi e bassi di espressione di FR⍺
- Robusta attività antitumorale e forte profilo di sicurezza in modelli preclinici
Zymeworks Inc. (Nasdaq: ZYME) anunció la aprobación de la FDA para su solicitud de Nuevo Medicamento en Investigación (IND) para ZW191, un novel conyugado anticuerpo-fármaco (ADC) dirigido al receptor de folato-⍺ (FR⍺) que actúa como inhibidor de la topoisomerasa I. ZW191 se dirige a tumores que expresan FR⍺, incluidos los tumores ováricos, cánceres ginecológicos y cáncer de pulmón no microcítico (NSCLC). El fármaco incorpora una combinación única de estabilidad del anticuerpo-conjugado y potencia del payload, con una fuerte actividad 'bystander'.
Las características clave de ZW191 incluyen:
- Una relación de anticuerpo-fármaco de ocho para una tolerabilidad y eficacia equilibradas
- Anticuerpo monoclonal FR⍺ generado internamente para una mejor internalización
- Capacidad para dirigirse a niveles altos, medios y bajos de expresión de FR⍺
- Robusta actividad antitumoral y fuerte perfil de seguridad en modelos preclínicos
Zymeworks Inc. (Nasdaq: ZYME)는 ZW191의 임상 시험 신약(IND) 신청이 FDA의 승인을 받았다고 발표했습니다. ZW191은 제1형 톱이성효소 억제제인 항체-약물 접합체(ADC)로, 엽산 수용체-⍺(FR⍺)에 타겟팅됩니다. ZW191은 FR⍺를 발현하는 종양을 표적으로 하며, 여기에는 난소, 부인과 암 및 비소세포 폐암(NSCLC)이 포함됩니다. 이 약물은 항체-링커 안정성과 유효성 향상에 독특한 조합을 통합하고 있으며, 강력한 비통제 활성(bystander activity)을 보여줍니다.
ZW191의 주요 특징에는 다음이 포함됩니다:
- 균형 잡힌 내약성과 효능을 위한 8:1의 약물-항체 비율
- 내부에서 생성된 FR⍺ 단클론 항체로 향상된 내부화
- FR⍺ 발현의 높은, 중간 및 낮은 수준을 표적으로 하는 능력
- 전임상 모델에서 강력한 항종양 활성 및 안전성 프로파일
Zymeworks Inc. (Nasdaq: ZYME) a annoncé l'approbation de la FDA de sa demande de Nouveau Médicament Expérimental (IND) pour ZW191, un nouveau conjugué anticorp-farmac (ADC) ciblant le récepteur folique-⍺ (FR⍺) en tant qu'inhibiteur de la topoisomérase I. ZW191 cible les tumeurs exprimant le FR⍺, y compris les cancers ovariens, les cancers gynécologiques et le cancer du poumon non à petites cellules (NSCLC). Le médicament intègre une combinaison unique de stabilité anticorps-linker et de puissance du chargeur, avec une forte activité de voisinage.
Les caractéristiques clés de ZW191 incluent :
- Un rapport médicament-anticorps de huit pour un bon équilibre entre tolérance et efficacité
- Anticorps monoclonal FR⍺ généré en interne pour une internalisation améliorée
- Capacité à cibler des niveaux d'expression élevés, moyens et faibles de FR⍺
- Activité antitumorale robuste et solide profil de sécurité dans des modèles précliniques
Zymeworks Inc. (Nasdaq: ZYME) hat die Genehmigung der FDA für ihren Antrag auf ein Investigational New Drug (IND) für ZW191, ein neuartiges Antikörper-Wirkstoff-Konjugat (ADC), das auf den Folsäure-Rezeptor-⍺ (FR⍺) abzielt, bekannt gegeben. ZW191 zielt auf FR⍺-exprimierende Tumoren ab, einschließlich Ovarial- und gynäkologischer Krebserkrankungen sowie nicht-kleinzelligem Lungenkrebs (NSCLC). Das Medikament kombiniert die Stabilität von Antikörper-Linkern und die Wirksamkeit des Wirkstoffs auf einzigartige Weise und bietet eine starke Nebenaktivität.
Wesentliche Merkmale von ZW191 umfassen:
- Ein Verhältnis von Antikörper zu Medikament von acht für ein ausgewogenes Verhältnis von Verträglichkeit und Wirksamkeit
- Intern generierter FR⍺-monoklonaler Antikörper für verbesserte Internalisierung
- Fähigkeit, hohe, mittlere und niedrige Ausdrucksniveaus von FR⍺ anzusprechen
- Robuste antitumorale Aktivität und starkes Sicherheitsprofil in präklinischen Modellen
- FDA clearance of IND application for ZW191, a novel antibody-drug conjugate
- ZW191 targets FR⍺-expressing tumors, including ovarian, gynecological cancers, and NSCLC
- Unique combination of antibody-linker stability and payload potency with strong bystander activity
- Robust anti-tumor activity and strong safety profile demonstrated in preclinical models
- Clinical development of ZW191 planned to initiate in 2024
- None.
Medical Research Analyst Perspective:
The FDA clearance for ZW191 is a significant milestone for Zymeworks. This novel folate receptor-⍺ targeted topoisomerase I inhibitor antibody-drug conjugate represents a promising advancement in the treatment of difficult-to-treat cancers like ovarian and non-small cell lung cancer (NSCLC). The clearance allows the company to proceed to clinical trials, where ZW191's efficacy and safety will be further tested in human subjects. This clearance reflects the quality and potential of Zymeworks' drug conjugate platforms and their TOPO1i-based payload technology, ZD06519, which offers a balanced approach between tolerability and efficacy due to its drug-antibody ratio of eight. The strong preclinical results showing robust anti-tumor activity and a strong safety profile bolster confidence in the upcoming clinical trials. Investors should watch the progress of ZW191 closely, as successful clinical results could significantly boost Zymeworks' market position.
Oncology Doctor Perspective:
The FDA clearance of ZW191 is noteworthy because it targets folate receptor-⍺, a clinically validated target present in a high percentage of ovarian and NSCLC cases. This makes ZW191 a potentially powerful tool in treating these cancers. The drug's ability to target various levels of FR⍺ expression is particularly promising, as it broadens its applicability across different patient profiles. Moreover, the novel antibody and drug-linker stability combined with strong bystander activity can potentially result in improved efficacy, important for hard-to-treat cancers. The anticipation of initiating clinical development for both ZW191 and ZW171 indicates Zymeworks' proactive approach in advancing its oncology pipeline, which could result in significant breakthroughs in cancer treatment.
Financial Analyst Perspective:
From a financial standpoint, the FDA clearance for ZW191 is an encouraging development for Zymeworks. It represents a critical step forward in the company's pipeline, potentially translating into significant future revenues if the clinical trials prove successful. The company's strategic focus on advancing multiple ADC molecules like ZW191, ZW220 and ZW251 positions it strongly in the competitive biotechnology market. This clearance follows closely after another FDA clearance for ZW171, suggesting a positive momentum and strong R&D capabilities. Investors should consider the potential long-term returns from Zymeworks' innovative approach, though they should also remain cautious until clinical trial results confirm the drug's efficacy and safety in humans.
VANCOUVER, British Columbia, July 22, 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 United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for ZW191, the Company’s novel folate receptor-⍺ (FR⍺) targeted topoisomerase I inhibitor (TOPO1i) antibody-drug conjugate (ADC).
“ZW191 is a differentiated product candidate in our pipeline that reflects the strength of our approach in developing best-in-class antibody-drug conjugates,” said Paul Moore, Chief Scientific Officer of Zymeworks. “Developed to target FR⍺, which is expressed in several types of difficult-to-treat cancers, ZW191 incorporates a novel antibody and drug-linker that provide a unique combination of antibody-linker stability and payload potency, together with strong bystander activity, which could result in improved efficacy and enable targeting lower levels of FR⍺ compared to previously developed drug candidates. We are pleased to reach this R&D milestone following on the heels of our recent FDA clearance for ZW171 in June and look forward to initiating clinical development of both ZW191 and ZW171 during 2024.”
ZW191 was designed using the Company’s drug conjugate platforms, including the novel TOPO1i-based payload technology, ZD06519, to target FR⍺-expressing tumors including ovarian and other gynecological cancers, as well as non-small cell lung cancer (NSCLC). A drug-antibody-ratio (DAR) of eight was selected to balance both tolerability and efficacy. The FR⍺ monoclonal antibody incorporated in ZW191 was generated in-house and selected based on enhanced internalization characteristics to enable targeting of high, mid, and low levels of FR⍺ expression. FR⍺ is a clinically validated target that is expressed in approximately
The Company expects to file applications seeking regulatory authorization to initiate clinical studies for ZW191 in non-US jurisdictions in the second half of 2024. ZW191 is the first of three ADC molecules incorporating the Company’s proprietary ZD06519 payload designated for clinical development, with IND filings for ZW220 (NaPi2b ADC) and ZW251 (GPC3 ADC) on schedule for 2025.
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 each of the U.S. and China. Zymeworks is rapidly advancing a deep pipeline of product candidates based on its experience and capabilities in both antibody-drug conjugates and multispecific antibody therapeutics across multiple novel targets in indications that represent areas of significant unmet medical need. In addition to Zymeworks’ wholly owned 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.
Cautionary Note Regarding 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 potential addressable market of Zymeworks’ product candidates; Zymeworks’ development of its product candidates; the timing and status of ongoing and future studies and the related data; expectations and timing regarding future regulatory filings and approvals; the timing of and results of interactions with regulators; potential safety profile and therapeutic effects of zanidatamab and Zymeworks’ other product candidates; the commercial potential of technology platforms and product candidates and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “continue”, “anticipate”, “potential”, “will”, “progress”, 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: 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; Zymeworks may not achieve milestones or receive additional payments under its collaborations; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; the impact of new or changing laws and regulations; market conditions; 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; clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; Zymeworks’ assumptions and estimates regarding its financial condition, future financial performance and estimated cash runway may be incorrect; 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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