Bolt Biotherapeutics Presents Updated Preclinical Data for BDC-4182 and Key Learnings from Phase 1 Dose-Escalation Trial of BDC-1001 at SITC 39th Annual Meeting
Bolt Biotherapeutics (BOLT) presented updated preclinical data for BDC-4182, their next-generation Boltbody™ ISAC targeting claudin 18.2, and findings from Phase 1 dose-escalation trial of BDC-1001 at SITC. BDC-4182 showed superior efficacy compared to claudin 18.2 ADCs in preclinical studies, demonstrating anti-tumor activity across various models and acceptable safety in non-human primates. The company plans to initiate clinical trials in 2025. The Phase 1 BDC-1001 trial revealed that greater immune activation was associated with clinical benefit, particularly in patients with high HER2 antigen expression, supporting the development of next-generation ISACs with enhanced immune activation.
Bolt Biotherapeutics (BOLT) ha presentato dati preclinici aggiornati per BDC-4182, il loro Boltbody™ ISAC di nuova generazione che mira a claudin 18.2, e i risultati dello studio clinico di Fase 1 con dose escalation di BDC-1001 al SITC. BDC-4182 ha mostrato un'efficacia superiore rispetto agli ADC a claudin 18.2 negli studi preclinici, dimostrando attività antitumorale attraverso diversi modelli e una sicurezza accettabile nei primati non umani. L'azienda prevede di iniziare la sperimentazione clinica nel 2025. Lo studio di Fase 1 di BDC-1001 ha rivelato che una maggiore attivazione immunitaria era associata a un beneficio clinico, in particolare nei pazienti con alta espressione di antigene HER2, supportando lo sviluppo di ISAC di nuova generazione con un'attivazione immunitaria potenziata.
Bolt Biotherapeutics (BOLT) presentó datos preclínicos actualizados para BDC-4182, su ISAC Boltbody™ de nueva generación dirigido a claudin 18.2, y los hallazgos del ensayo clínico de Fase 1 de dosis escalonadas de BDC-1001 en el SITC. BDC-4182 mostró una eficacia superior en comparación con los ADC de claudin 18.2 en estudios preclínicos, demostrando actividad antitumoral en varios modelos y una seguridad aceptable en primates no humanos. La compañía planea iniciar ensayos clínicos en 2025. El ensayo de Fase 1 de BDC-1001 reveló que una mayor activación inmune se asociaba con un beneficio clínico, particularmente en pacientes con alta expresión del antígeno HER2, respaldando el desarrollo de ISAC de nueva generación con una activación inmune mejorada.
볼트 바이오테라퓨틱스 (BOLT)는 BDC-4182에 대한 업데이트된 전임상 데이터를 발표했으며, 이는 클라우딘 18.2를 표적으로 하는 차세대 Boltbody™ ISAC입니다. SITC에서 BDC-1001의 1상 용량 증량 시험 결과도 제시되었습니다. BDC-4182는 전임상 연구에서 클라우딘 18.2 ADC보다 우수한 효능을 보여주었고, 다양한 모델에서 항종양 활성을 입증하며 비인간 영장류에서 수용 가능한 안전성을 보였습니다. 이 회사는 2025년에 임상 시험을 시작할 계획입니다. BDC-1001의 1상 시험에서는 면역 활성화가 특히 HER2 항원 발현이 높은 환자에서 임상적 이점과 관련이 있다는 사실이 밝혀졌으며, 이는 향상된 면역 활성화와 함께 차세대 ISAC 개발을 뒷받침합니다.
Bolt Biotherapeutics (BOLT) a présenté des données précliniques à jour pour BDC-4182, leur ISAC Boltbody™ de nouvelle génération ciblant la claudine 18.2, ainsi que les résultats de l'essai de phase 1 d'escalade de dose de BDC-1001 lors du SITC. BDC-4182 a montré une efficacité supérieure par rapport aux ADC de claudine 18.2 dans des études précliniques, démontrant une activité antitumorale dans divers modèles et une sécurité acceptable chez des primates non humains. L'entreprise prévoit de commencer des essais cliniques en 2025. L'essai de phase 1 de BDC-1001 a révélé qu'une plus grande activation immunitaire était associée à un bénéfice clinique, en particulier chez les patients exprimant des niveaux élevés d'antigène HER2, soutenant le développement d'ISAC de nouvelle génération avec une activation immunitaire améliorée.
Bolt Biotherapeutics (BOLT) hat aktualisierte vorklinische Daten zu BDC-4182 vorgestellt, ihrem nächsten Boltbody™ ISAC, der auf Claudin 18.2 abzielt, sowie Ergebnisse aus der Phase-1-Dosissteigerungsstudie zu BDC-1001 beim SITC. BDC-4182 zeigte in vorklinischen Studien eine überlegene Wirksamkeit im Vergleich zu Claudin 18.2 ADCs, indem es antitumorale Aktivität in verschiedenen Modellen und eine akzeptable Sicherheit bei nichtmenschlichen Primaten demonstrierte. Das Unternehmen plant, 2025 klinische Studien zu beginnen. Die Phase-1-Studie zu BDC-1001 ergab, dass eine stärkere Immunaktivierung mit einem klinischen Nutzen assoziiert war, insbesondere bei Patienten mit hoher HER2-Antigenexpression, was die Entwicklung von ISAC der nächsten Generation mit verbesserter Immunaktivierung unterstützt.
- BDC-4182 demonstrated superior efficacy compared to existing claudin 18.2 ADCs in preclinical studies
- BDC-4182 showed anti-tumor activity in tumors with low claudin 18.2 expression
- Acceptable safety profile in non-human primates for BDC-4182
- Clinical trial initiation for BDC-4182 on track for 2025
- BDC-1001 showed efficacy in patients with lower HER2 expression levels
Insights
The preclinical data for BDC-4182 shows promising developments in targeting claudin 18.2-expressing cancers. Key highlights include superior efficacy compared to traditional ADCs and activity against tumors with low claudin 18.2 expression. The compound's ability to generate immunological memory and demonstrate acceptable safety in non-human primates is particularly noteworthy.
The Phase 1 learnings from BDC-1001 provide valuable insights for future ISAC development. The correlation between immune activation and clinical benefit, especially in HER2 IHC3+ patients, validates the ISAC approach while suggesting room for improvement in next-generation compounds. The planned 2025 clinical trial initiation for BDC-4182 represents a significant milestone in the company's pipeline development.
BDC-4182 demonstrated compelling anti-tumor activity and an acceptable safety profile in preclinical studies
BDC-4182 outperformed cytotoxic claudin 18.2 ADCs in syngeneic model
Learnings from BDC-1001 data suggest Boltbody™ ISACs with enhanced immune activation could offer greater efficacy, warranting further testing
REDWOOD CITY, Calif., Nov. 07, 2024 (GLOBE NEWSWIRE) -- Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, today presented updated preclinical data for BDC-4182, a next-generation Boltbody™ ISAC clinical candidate targeting claudin 18.2, and provided key learnings from its Phase 1 dose-escalation trial of BDC-1001 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), being held in Houston, Texas from November 6-10, 2024.
“We are encouraged by the preclinical BDC-4182 data presented at SITC. Most notably, our next-generation claudin 18.2 ISAC elicits better efficacy than claudin 18.2 ADCs in syngeneic tumor models and can eradicate tumors with low claudin 18.2 expression. We look forward to dosing our first patient in BDC-4182 in 2025,” said Michael Alonso, Ph.D., Senior Vice President of Research. “Our key learnings from the Phase 1 BDC-1001 dose escalation trial that are being presented at SITC support our belief that next-generation Boltbody™ ISACs with enhanced immune activation will offer greater efficacy with the potential for durable responses.”
BDC-4182 is a next-generation Boltbody™ ISAC clinical candidate targeting claudin 18.2, a clinically validated target in oncology with expression in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. BDC-4182 has advanced into IND-enabling activities, supported by in vitro and in vivo experiments demonstrating potent anti-tumor activity in multiple preclinical models, with clinical trial initiation expected in 2025. In vivo assessment of anti-tumor activity was performed with a murine surrogate of BDC-4182 using xenograft and syngeneic tumor models with different levels of claudin 18.2 expression. The tolerability of BDC-4182 was also tested in non-human primates (NHPs). Key findings are summarized below.
- BDC-4182 demonstrated superior efficacy compared to cytotoxic claudin 18.2 ADCs
- BDC-4182 demonstrated anti-tumor activity in a wide range of tumor models and elicits immunological memory
- BDC-4182 has an acceptable safety profile in NHPs with findings consistent with TLR7/8 activation and claudin 18.2 targeting
- BDC-4182 toxicology profile may enable combinations with checkpoint inhibitors, chemotherapy and anti-angiogenesis agents used in first-line and second-line treatments
Key learnings from the Phase 1 dose escalation trial of BDC-1001 are summarized below.
- First-generation ISAC BDC-1001 demonstrated immunological activity in this first-in-human trial, particularly in patients with high HER2 antigen expression
- Greater immune activation was associated with clinical benefit
- Pharmacodynamic changes were observed in HER2 IHC3+ and HER2 IHC2+, with both the greatest increase and statistical significance in patients with HER2 IHC 3+ tumors
- Data supports the hypothesis that an ISAC with enhanced immune activation could offer greater efficacy, warranting further testing in next-generation ISACs
Details about the BDC-1001 oral presentation and the BDC-4182 poster presentation can be found on the SITC website. Additionally, copies of the presentations are available on the publications page of the Bolt Biotherapeutics website.
Title: Preclinical Activity of BDC-4182, a Claudin 18.2-Targeting ISAC with Enhanced Potency and an Encouraging Safety Profile
Presenter: Han Kim, Ph.D., Bolt Biotherapeutics
Session Date and Time: Saturday, November 9, 2024, 9:00 a.m. – 8:30 p.m. CT
Location: Exhibit Halls A B George R. Brown Convention Center
Abstract Number: 1052
Title: Key Learnings from BDC-1001 Phase 1 FIH Dose Escalation Trial Inform Next-generation ISACs
Presenter: Jason Ptacek, Ph.D., Bolt Biotherapeutics
Session Date and Time: Saturday, November 9, 2024, 5:15 p.m. – 6:35 p.m. CT
Location: George R. Brown Convention Center - Level 3 - Grand Ballroom C
Abstract Number: 30
About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Program
Bolt Biotherapeutics’ Boltbody™ ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.
About Bolt Biotherapeutics, Inc.
Bolt Biotherapeutics is a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer. Bolt Biotherapeutics’ pipeline candidates are built on the Company’s deep expertise in myeloid biology and cancer drug development. The Company’s pipeline includes BDC-3042, a first-in-class agonist antibody that activates macrophages by targeting Dectin-2, and BDC-4182, a next-generation Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) clinical candidate targeting claudin 18.2. BDC-3042 is currently in a Phase 1 dose escalation trial that includes patients with any of seven different solid tumor types. BDC-4182 is supported by strong in vitro and in vivo data demonstrating potent anti-tumor activity, and activities are underway to support the initiation of clinical trials in 2025. Bolt Biotherapeutics is also developing additional Boltbody ISACs in strategic collaborations with leading biopharmaceutical companies. For more information, please visit https://www.boltbio.com/.
Forward-Looking Statements
This press release contains forward-looking statements about us and our industry that involve substantial risks and uncertainties and are based on our beliefs and assumptions and on information currently available to us. All statements other than statements of historical facts contained in this press release, including statements regarding the potential initiation of clinical trials for BDC-4182, the anti-tumor potency, safety and tolerability, and characteristics of our product candidates, and the initiation of future clinical trials, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “on track,” “plan,” “potential,” “predict,” “project,” “should,” “will,” or “would,” or the negative of these words or other similar terms or expressions. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements represent our current beliefs, estimates and assumptions only as of the date of this press release and information contained in this press release should not be relied upon as representing our estimates as of any subsequent date. These statements, and related risks, uncertainties, factors and assumptions, include, but are not limited to: the potential product candidates that we develop may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; such product candidates may not be beneficial to patients or become commercialized; and our ability to maintain our current collaborations and establish further collaborations. These risks are not exhaustive. Except as required by law, we assume no obligation to update these forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Further information on factors that could cause actual results to differ materially from the results anticipated by our forward-looking statements is included in the reports we have filed or will file with the Securities and Exchange Commission, including our Annual Report on Form 10-K for the year ended December 31, 2023. These filings, when available, are available on the investor relations section of our website at investors.boltbio.com and on the SEC’s website at www.sec.gov.
Investor Relations and Media Contact:
Matthew DeYoung
Argot Partners
(212) 600-1902
boltbio@argotpartners.com
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