Ambrx Biopharma presents new preclinical data on ARX517, ARX305

Ambrx Biopharma, or Ambrx, announced new preclinical data at the 2023 American Association for Cancer Research, AACR, Annual Meeting in Orlando, Florida, held from April 14 to 19, 2023. Poster Title: ARX517, a Next-Generation anti-PSMA Antibody Drug Conjugate for the Treatment of Metastatic Castration-Resistant Prostate Cancer, Demonstrates Anti-Tumor Activity in Enzalutamide-Resistant and Enzalutamide-Sensitive Models and a Clear Therapeutic Index in a Non-Human Primate Model. Highlights: The stability of ARX517 was demonstrated in a non-human primate study; Pharmacokinetic measurements confirm the high stability of ARX517 in circulation with an extended half-life of 11 or 15 days; The main metabolite of ARX517 cytotoxic linker payload, pAF-AS269, was barely measurable in the serum in repeat dosing study; At the highest non-severely toxic dose, ARX517 serum exposure was greater than ARX517 exposure at a pharmacologically active dose in mice, showing a clear therapeutic index; In enzalutamide-sensitive mouse model of prostate cancer, ARX517 clearly demonstrated anti-tumor activity, further the combination of 3 mg/kg ARX517 plus 10 mg/kg enzalutamide delivered an 86% reduction in tumor size; In an enzalutamide-resistant prostate cancer model, three weekly doses of 3 mg/kg of ARX517 significantly inhibited tumor growth by 79% in a dose-dependent manner; In summary, ARX517 exhibits anti-tumor activity in preclinical enzalutamide-resistant and enzalutamide-sensitive prostate cancer models, with high stability in circulation and demonstrates a clear therapeutic index in a non-human primate model. Poster title: ARX517, an anti-PSMA ADC targeting mCRPC resistant or refractory to standard therapies: A phase 1 dose escalation and dose expansion study. Highlights: Ambrx is currently investigating ARX517 in the APEX-01 first-in-human Phase 1, multicenter, dose escalation and dose expansion clinical study to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of ARX517 in adult subjects and is currently enrolling patients with advanced prostate cancer whose tumors have progressed following at least two FDA approved treatments for prostate cancer and have met one of the following three criteria: PSA progression defined by a minimum of 2 rising PSA values or radiographic progression by RECIST v 1.1 or disease progression by the presence of new bone lesions. The latest dosing cohort was recently initiated at 2.9 mg/kg. APEX-01 is the only ongoing clinical trial in the United States targeting PSMA with an ADC. Poster Title: Preclinical characterization of ARX305, a next-generation anti-CD70 antibody drug conjugate for the treatment of CD70-expressing cancers. Key Highlights: In a renal cell carcinoma xenograph model, ARX305 dose-dependently inhibited tumor growth and outperformed sunitinib; In another RCC xenograph model, weekly administration of ARX305 resulted in significant, dose-dependent, anti-tumor activity; Pharmacokinetic studies of ARX305 in mice confirms the high ADC stability in circulation with a long terminal half-life of 16.5 days; GLP toxicity study in monkey predicted a clear therapeutic index in human; In summary, ARX305 preclinical data demonstrated ADC stability, strong anti-tumor activity in two RCC models, increased survival of animals in a multiple myeloma disseminated model, and tolerance in non-human primates indicating a wide therapeutic index.