SAN DIEGO, CA, USA I April 19, 2023 I Ambrx Biopharma Inc., or Ambrx (NASDAQ: AMAM), 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.

Ambrx’s presentations highlight data from preclinical studies of ARX517, the only anti-PSMA ADC in clinical development, and ARX305, one of two anti-CD70 ADCs in active clinical development. A trial in progress update on APEX-01, Ambrx’s first-in-human, Phase 1, dose-escalation clinical study of ARX517, was also presented.

Highlights from Ambrx’s presentations are included below.

Presentation Highlights:

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

Published Abstract Number: 3997
Key Highlights:

  • The stability of ARX517 was demonstrated in a non-human primate (monkey) 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 (0.2 ng/mL) in the serum in repeat dosing study
  • At the highest non-severely toxic dose (HNSTD), 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 (APEX-01 NCT04662580)
Abstract Presentation Number: CT121
Key Highlights:

Ambrx is currently investigating ARX517 in the APEX-01 (NCT04662580) 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
Published Abstract Number: 6318
Key Highlights:

  • In a renal cell carcinoma (RCC, 786-OS3) xenograph model, ARX305 dose-dependently inhibited tumor growth and outperformed sunitinib
  • In another RCC (Caki-1) 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

About Ambrx Biopharma Inc.
Ambrx is a clinical stage biopharmaceutical company using an expanded genetic code technology platform to discover and develop next generation antibody drug conjugates (ADCs) and other engineered therapies to modulate the immune system. Ambrx is advancing a focused portfolio of clinical and preclinical programs designed to optimize efficacy and safety in multiple cancer indications, including ARX517, its proprietary antibody-drug conjugate (ADC) targeting the prostate-specific membrane antigen (PSMA) and ARX788, its proprietary ADC targeting HER2. In addition, Ambrx has preclinical and clinical collaborations with multiple partners on drug candidates generated using Ambrx technology. Ambrx spun out of The Scripps Research Institute in 2003 and has several other product candidates involving ADCs and other aspects of Ambrx’s protein engineering technology. For more information, please visit or follow us on Twitter, LinkedIn, and Facebook. Ambrx routinely posts information that may be important to investors on its website.

Electronic versions of the poster presentations can be found on Ambrx’s website.