Bicycle Therapeutics Announces Data Updates Across Zelenectide Pevedotin Program and Development Strategy Leveraging NECTIN4 Gene Amplification
Bicycle Therapeutics (NASDAQ: BCYC) announced significant data updates for its zelenectide pevedotin program. The drug showed a 60% overall response rate when combined with pembrolizumab in first-line metastatic urothelial cancer. In breast cancer patients with NECTIN4 gene amplification, the drug demonstrated a 62.5% response rate, while NSCLC patients with NECTIN4 gene amplification showed a 40% response rate.
The company plans to advance its development strategy focusing on NECTIN4 gene amplification, with Phase 1/2 trials in breast cancer, lung cancer, and multi-tumor planned for 2025. Dose selection and topline data from the Phase 2/3 Duravelo-2 trial are expected in 2H 2025.
Bicycle Therapeutics (NASDAQ: BCYC) ha annunciato aggiornamenti significativi sui dati del suo programma di pevedotina zelenectide. Il farmaco ha mostrato un tasso di risposta complessivo del 60% quando combinato con pembrolizumab nel carcinoma uroteliale metastatico di prima linea. Nei pazienti con cancro al seno con amplificazione del gene NECTIN4, il farmaco ha dimostrato un tasso di risposta del 62,5%, mentre i pazienti con NSCLC con amplificazione del gene NECTIN4 hanno mostrato un tasso di risposta del 40%.
La società prevede di avanzare nella sua strategia di sviluppo concentrandosi sull'amplificazione del gene NECTIN4, con studi clinici di Fase 1/2 in cancro al seno, cancro ai polmoni e tumori multipli pianificati per il 2025. La selezione della dose e i dati preliminari dalla sperimentazione Duravelo-2 di Fase 2/3 sono attesi per la seconda metà del 2025.
Bicycle Therapeutics (NASDAQ: BCYC) anunció actualizaciones significativas de datos para su programa de pevedotina zelenectide. El medicamento mostró una tasa de respuesta general del 60% cuando se combina con pembrolizumab en cáncer urotelial metastásico de primera línea. En pacientes con cáncer de mama con amplificación del gen NECTIN4, el medicamento demostró una tasa de respuesta del 62,5%, mientras que los pacientes con NSCLC con amplificación del gen NECTIN4 mostraron una tasa de respuesta del 40%.
La compañía planea avanzar en su estrategia de desarrollo enfocándose en la amplificación del gen NECTIN4, con ensayos de Fase 1/2 en cáncer de mama, cáncer de pulmón y múltiples tumores previstos para 2025. La selección de dosis y los datos preliminares del ensayo Duravelo-2 de Fase 2/3 se esperan para la segunda mitad de 2025.
바이시클 테라퓨틱스 (NASDAQ: BCYC)는 제약 프로그램인 제레넥타이드 페베도틴에 대한 중요한 데이터 업데이트를 발표했습니다. 이 약물은 1차 전이성 요로 세포 암에서 펨브롤리주맙과 병합했을 때 60%의 전체 반응률을 보였습니다. NECTIN4 유전자 증폭을 가진 유방암 환자에서는 62.5%의 반응률을 나타냈고, NECTIN4 유전자 증폭을 가진 비소세포 폐암(NSCLC) 환자들은 40%의 반응률을 보였습니다.
회사는 NECTIN4 유전자 증폭에 초점을 맞춘 개발 전략을 추진할 계획이며, 유방암, 폐암 및 다종 양성 종양에 대한 1/2상 임상시험이 2025년으로 예정되어 있습니다. 2/3상 Duravelo-2 시험에서의 용량 선택 및 주요 데이터는 2025년 하반기에 발표될 예정입니다.
Bicycle Therapeutics (NASDAQ: BCYC) a annoncé des mises à jour de données significatives pour son programme de pevedotine zelenectide. Le médicament a montré un taux de réponse global de 60% lorsqu'il était combiné avec le pembrolizumab dans le cancer urotélial métastatique de première ligne. Chez les patients atteints de cancer du sein avec amplification du gène NECTIN4, le médicament a démontré un taux de réponse de 62,5%, tandis que les patients atteints de NSCLC avec amplification du gène NECTIN4 ont affiché un taux de réponse de 40%.
L'entreprise envisage d'avancer sa stratégie de développement en se concentrant sur l'amplification du gène NECTIN4, avec des essais de Phase 1/2 dans le cancer du sein, le cancer du poumon et les tumeurs multiples prévus pour 2025. Le choix de la dose et les données préliminaires de l'essai Duravelo-2 de Phase 2/3 sont attendus pour le second semestre 2025.
Bicycle Therapeutics (NASDAQ: BCYC) hat bedeutende Datenaktualisierungen für sein Zelenectide-Pevedotin-Programm bekannt gegeben. Das Medikament zeigte eine 60%ige Gesamtansprechrate in Kombination mit Pembrolizumab bei metastasiertem Urothelkarzinom der ersten Linie. Bei Brustkrebspatienten mit NECTIN4-Gentypisierung wies das Medikament eine 62,5%ige Ansprechrate auf, während NSCLC-Patienten mit NECTIN4-Gentypisierung eine 40%ige Ansprechrate zeigten.
Das Unternehmen plant, seine Entwicklungsstrategie mit Fokus auf die NECTIN4-Gentypisierung voranzutreiben, wobei Phase 1/2-Studien für Brustkrebs, Lungenkrebs und vieles mehr für 2025 geplant sind. Die Dosisauswahl und die ersten Ergebnisse der Phase 2/3 Duravelo-2-Studie werden für die zweite Hälfte von 2025 erwartet.
- 60% overall response rate in first-line metastatic urothelial cancer combination therapy
- 62.5% response rate in breast cancer patients with NECTIN4 gene amplification
- 40% response rate in NSCLC patients with NECTIN4 gene amplification
- Generally well-tolerated safety profile with primarily low-grade adverse events
- Small sample sizes in NECTIN4 gene amplification studies
- Several unconfirmed responses in the data
- response in patients without NECTIN4 gene amplification
Insights
Topline combination data for zelenectide pevedotin plus pembrolizumab in first-line metastatic urothelial cancer demonstrated a
Dose selection and topline data from Phase 2/3 Duravelo-2 trial planned for 2H 2025
Heavily pretreated breast cancer and non-small cell lung cancer patients with NECTIN4 gene amplification and/or polysomy demonstrated an enhanced response to zelenectide pevedotin
Company to advance development strategy leveraging NECTIN4 gene amplification, with Phase 1/2 trials in breast cancer, lung cancer and multi-tumor planned for 2025
Bicycle Therapeutics to host conference call and webcast with management and oncology experts on Friday, Dec. 13, at 8 a.m. ET
“The totality of the data shared today builds on the breadth of previously reported data for zelenectide pevedotin that we believe, when combined with our ambitious development strategy leveraging NECTIN4 gene amplification, position Bicycle as a leader in addressing Nectin-4 associated cancers,” said Bicycle Therapeutics CEO Kevin Lee, Ph.D. “We are encouraged by the topline zelenectide pevedotin data in combination with pembrolizumab in first-line mUC patients, which demonstrate zelenectide pevedotin’s response data are in line with other drug conjugates used to treat mUC while its safety and tolerability profile continues to be differentiated. Additionally, we are very pleased with our progress in enrolling our Duravelo-2 registrational trial for zelenectide pevedotin in mUC and look forward to providing dose selection and topline data in the second half of next year.”
Dr. Lee continued: “While early, the zelenectide pevedotin monotherapy data in breast cancer and NSCLC patients with NECTIN4 gene amplification underscore its promising anti-tumor activity and solidify our next steps for the therapy’s development. By leveraging NECTIN4 gene amplification, we expect to be able to identify the patients who may most benefit from zelenectide pevedotin and accelerate development for solid tumor indications beyond bladder cancer. Over the course of 2025, we plan to initiate Phase 1/2 trials evaluating zelenectide pevedotin in NECTIN4 gene-amplified breast cancer, lung cancer and multiple other cancers.”
Topline Zelenectide Pevedotin Plus Pembrolizumab Combination Data in First-line mUC Highlights
Zelenectide pevedotin is a Bicycle® Toxin Conjugate (BTC®) targeting Nectin-4, a well-validated tumor antigen. Topline results from the ongoing Phase 1/2 Duravelo-1 trial evaluating zelenectide pevedotin 5 mg/m2 weekly plus pembrolizumab 200 mg once every three weeks in 22 first-line cisplatin-ineligible patients with mUC showed:
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60% overall response rate (ORR) (12/20) among efficacy-evaluable patients. Of the responses, 5 were confirmed and 7 were unconfirmed at the time of the data cut. Fifteen patients remained on treatment at the time of the data cut. - Safety and tolerability profile was broadly consistent with late-line Duravelo-1 monotherapy and combination cohorts.
- Adverse events of clinical interest such as peripheral neuropathy, skin reactions and eye disorders were primarily low grade. There was one report of Grade 3 sensory peripheral neuropathy and one report of Grade 3 rash, both of which were transient and reverted to Grade 1 upon dose interruption.
More detailed data from this study will be presented at a future medical meeting.
Bicycle Therapeutics is currently conducting the Phase 2/3 Duravelo-2 trial evaluating zelenectide pevedotin plus pembrolizumab versus chemotherapy in first-line mUC (Cohort 1), and zelenectide pevedotin monotherapy and in combination with pembrolizumab in late-line mUC (Cohort 2). In each cohort, two doses of zelenectide pevedotin – 5 mg/m2 weekly and 6 mg/m2 two weeks on, one week off – are being initially assessed. Based on enrollment progress, the company plans to report dose selection and topline data for both cohorts in the second half of 2025.
Zelenectide Pevedotin Monotherapy Data in Breast Cancer Patients with NECTIN4 Gene Amplification Highlights (Presented at 2024 SABCS)
Gene amplification is a common mechanism by which cancer cells gain function. Bicycle Therapeutics identified that the NECTIN4 gene sits on a commonly amplified chromosomal site in cancer, creating more copies of the gene and often translating to more protein expression. Since zelenectide pevedotin binds to Nectin-4, it was hypothesized that NECTIN4 gene amplification may predict response and could serve as a biomarker for therapy stratification.
The company conducted a post-hoc analysis of 38 heavily pretreated breast cancer patients enrolled in Duravelo-1, of which 32 were confirmed to have triple-negative breast cancer (TNBC). The majority of patients were treated with zelenectide pevedotin 5 mg/m2 weekly.
Of the 38 breast cancer patients enrolled, 35 patients were efficacy evaluable. Additionally, 23 breast cancer patient samples were available for NECTIN4 testing, of which 8 demonstrated NECTIN4 gene amplification or harbored NECTIN4 polysomy. Results showed:
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62.5% ORR (5/8) among breast cancer patients with NECTIN4 gene amplification or polysomy, compared to14.3% ORR (5/35) among all efficacy-evaluable breast cancer patients. - Of the 5 partial responses, 4 were confirmed and 1 was unconfirmed.
- No responses in non-amplified or non-polysomy patients.
Of the 32 TNBC patients enrolled, 30 patients were efficacy evaluable. Additionally, 19 TNBC patient samples were available for NECTIN4 testing, of which 7 demonstrated NECTIN4 gene amplification or harbored a NECTIN4 polysomy. Results showed:
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57.1% ORR (4/7) among TNBC patients with NECTIN4 gene amplification or polysomy, compared to13.3% ORR (4/30) among all efficacy-evaluable TNBC patients. - Of the 4 partial responses, 3 were confirmed and 1 was unconfirmed.
- All 3 TNBC patients with NECTIN4 gene amplification who responded to zelenectide pevedotin had prior treatment with sacituzumab govitecan.
- No responses in non-amplified or non-polysomy patients.
In this study of heavily pretreated breast cancer patients, zelenectide pevedotin was generally well tolerated, and its safety and tolerability profile was consistent with data from other Duravelo-1 cohorts. Low rates of Grade ≥3 treatment-related adverse events (TRAEs) (
“Although the sample size was limited, this post-hoc analysis highlights the encouraging anti-tumor activity of zelenectide pevedotin in breast cancer patients with NECTIN4 gene amplification, particularly among those with TNBC who urgently need new treatment options,” said Professor Sherene Loi, M.D., Ph.D., consultant medical oncologist in the Breast Unit and group leader at the Peter MacCallum Cancer Centre in
The poster presentation, “Enhanced anti-tumor activity of zelenectide pevedotin in triple-negative breast cancer (TNBC) patients with NECTIN4 gene amplification” is available in the Publications section of the Bicycle Therapeutics website.
Topline Zelenectide Pevedotin Monotherapy Data in NSCLC Patients with NECTIN4 Gene Amplification Highlights
The company conducted a post-hoc analysis of 40 pretreated patients with NSCLC enrolled in Duravelo-1. The majority of patients received zelenectide pevedotin 5 mg/m2 weekly.
Of the 40 patients enrolled, 34 patients were efficacy evaluable. Additionally, 19 patient samples were available for NECTIN4 testing, of which 6 demonstrated NECTIN4 gene amplification. Five out of 6 patients with NECTIN4 gene amplification were efficacy evaluable. Results showed:
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40.0% ORR (2/5) among patients with NECTIN4 gene amplification, compared to8.8% ORR (3/34) among all efficacy-evaluable patients. - Of the 3 partial responses, 2 were confirmed and 1 was unconfirmed.
- Out of 19 patients tested for NECTIN4 gene amplification, none of the non-amplified patients responded.
The safety and tolerability profile of zelenectide pevedotin was broadly consistent with data from other Duravelo-1 monotherapy cohorts.
More detailed data from this study will be presented at a future medical meeting.
Overview of Development Strategy Leveraging NECTIN4 Gene Amplification
Bicycle Therapeutics plans to advance development of zelenectide pevedotin in broader indications outside of mUC utilizing a NECTIN4 gene amplification strategy to target patients who have the potential for significantly deeper responses.
Over the course of 2025, Bicycle Therapeutics plans to initiate several additional Phase 1/2 trials to assess zelenectide pevedotin in NECTIN4 gene-amplified breast cancer, lung cancer and multiple other cancers. Through this strategy, the company believes it has the opportunity to become the leader in addressing Nectin-4 associated cancers and potentially transform the treatment landscape for thousands of patients in
Conference Call Details
Bicycle Therapeutics will host a conference call and webcast on Friday, Dec. 13, at 8 a.m. ET to review the data updates for zelenectide pevedotin. The company’s management team will be joined by Sherene Loi, M.D., Ph.D., Peter MacCallum Cancer Centre, and Niklas Klümper, M.D., University Hospital Bonn.
To access the call, please dial +1-833-816-1408 (
About Bicycle Therapeutics
Bicycle Therapeutics is a clinical-stage pharmaceutical company developing a novel class of medicines, referred to as Bicycle® molecules, for diseases that are underserved by existing therapeutics. Bicycle molecules are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity, making Bicycle molecules attractive candidates for drug development. The company is evaluating zelenectide pevedotin (formerly BT8009), a Bicycle® Toxin Conjugate (BTC®) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC molecule targeting EphA2, a historically undruggable target; and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist® (Bicycle TICA®) targeting Nectin-4 and agonizing CD137, in company-sponsored clinical trials. Additionally, the company is developing Bicycle Radionuclide Conjugates (BRC®) for radiopharmaceutical use and, through various partnerships, is exploring the use of Bicycle® technology to develop therapies for diseases beyond oncology.
Bicycle Therapeutics is headquartered in
Forward Looking Statements
This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Bicycle’s development of zelenectide pevedotin, BT5528 and BT7480 as well as potential radiopharmaceutical product candidates; the company’s plans to utilize a NECTIN4 gene amplification strategy in the clinical development of zelenectide pevedotin; expectations with respect to Bicycle’s ability to identify the patients who may most benefit from zelenectide pevedotin, to advance or accelerate development of this product candidate for broader indications, including solid tumor cancers beyond bladder cancer, and to become a leader in addressing Nectin-4 associated cancers; the planned initiation of clinical trials of zelenectide pevedotin in breast cancer, lung cancer, and other cancers; the timing and manner of announcement of data and program updates from clinical trials for zelenectide pevedotin, including reporting of dose selection and topline data from the Duravelo-2 trial; and the use of Bicycle’s technology through various partnerships to develop potential therapies in diseases beyond oncology. Bicycle may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in research and development and in the initiation, progress and completion of clinical trials and clinical development of Bicycle’s product candidates; the risk that Bicycle may not realize the intended benefits of its technology, partnerships or NECTIN4 gene amplification strategy; timing of results from clinical trials; whether the outcomes of preclinical studies and prior clinical trials will be predictive of future clinical trial results; the risk that trials may have unsatisfactory outcomes; potential adverse effects arising from the testing or use of Bicycle’s product candidates; and other important factors, any of which could cause Bicycle’s actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on October 31, 2024, as well as in other filings Bicycle may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Bicycle expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.
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Investors:
Stephanie Yao
SVP, Investor Relations and Corporate Communications
stephanie.yao@bicycletx.com
857-523-8544
Matthew DeYoung
Argot Partners
ir@bicycletx.com
212-600-1902
Media:
Jim O’Connell
Weber Shandwick
media@bicycletx.com
312-988-2343
Source: Bicycle Therapeutics plc
FAQ
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