Ambrx Presents New Preclinical Data on ARX517 and ARX305 at the 2023 AACR Annual Meeting

Rhea-AI Summary

Ambrx Biopharma (NASDAQ: AMAM) announced promising preclinical data at the 2023 AACR Annual Meeting. Key highlights include data on ARX517, an anti-PSMA ADC, which showed significant anti-tumor activity in enzalutamide-resistant and sensitive prostate cancer models. In a non-human primate study, ARX517 displayed high stability with a half-life of 11 to 15 days. In a separate study, ARX305 demonstrated strong anti-tumor effects in renal cell carcinoma models, exhibiting a terminal half-life of 16.5 days. The APEX-01 trial for ARX517, targeting advanced prostate cancer, is ongoing, with the latest cohort initiated at 2.9 mg/kg. Ambrx focuses on developing next-generation ADCs, aiming to improve treatment outcomes in various cancers.

Positive

• ARX517 shows anti-tumor activity in both enzalutamide-sensitive and resistant prostate cancer models, achieving an 86% tumor size reduction.
• High stability of ARX517 confirmed by a non-human primate study with an extended half-life of 11-15 days.
• ARX305 demonstrates significant anti-tumor effects in two renal cell carcinoma models.
• APEX-01 clinical trial for ARX517 is ongoing, indicating progress in cancer treatment development.

Negative

• None.

SAN DIEGO, April 19, 2023 (GLOBE NEWSWIRE) -- 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 www.ambrx.com 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.

Forward-Looking Statements
This press release includes certain “forward-looking statements” intended to qualify for the “safe harbor” from liability established by the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements may be identified by the words “intend,” “plan,” and similar expressions, and include, without limitation, express or implied statements regarding Ambrx’s beliefs and expectations regarding the potential benefits of ARX517 and ARX305, development and strategic plans for ARX517 and ARX305 and the timing of data updates and milestones related to ARX517 and ARX305. Forward-looking statements are based on Ambrx’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, those risks and uncertainties associated with: the continuing impact of the COVID-19 pandemic and other public health-related risks and events on Ambrx’s business, operations, strategy, goals and anticipated milestones; Ambrx’s ability to execute on its strategy including with respect to the timing of its R&D efforts, initiation of clinical trials and other anticipated milestones; risks associated with development and marketing approval of novel therapeutics, including potential delays in clinical trials and regulatory submissions and the fact that future clinical trial results/data may not be consistent with interim, initial or preliminary results/data or results/data from prior preclinical studies or clinical trials; Ambrx’s ability to fund operations as anticipated; and the additional risks and uncertainties set forth more fully under the caption “Risk Factors” in Ambrx’s Annual Report on Form 10-K filed with the SEC on March 30, 2023, and elsewhere in Ambrx’s filings and reports with the SEC. Forward-looking statements contained in this press release are made as of this date, and Ambrx undertakes no duty to publicly update or revise any forward looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable law.

Contacts

INVESTORS
Mike Moyer
LifeSci Advisors
617-308-4306
mmoyer@lifesciadvisors.com

MEDIA
Mike Tattory
Account Supervisor 
LifeSci Communications 
media@ambrx.com

Source: Ambrx Biopharma Inc.

FAQ

What are the results of Ambrx's APEX-01 trial for ARX517?

The APEX-01 trial is ongoing and aims to evaluate the safety and preliminary anti-tumor activity of ARX517 in patients with advanced prostate cancer.

What is the significance of the preclinical data presented by Ambrx for ARX517?

The preclinical data suggest that ARX517 has significant anti-tumor activity and high stability, which may enhance its therapeutic potential.

How does ARX305 compare to existing treatments for renal cell carcinoma?

ARX305 has shown superior anti-tumor activity in preclinical models compared to sunitinib, indicating its potential as a more effective treatment.

What key highlights were presented for ARX517 at the AACR 2023 meeting?

ARX517 demonstrated a clear therapeutic index in non-human primates and significant anti-tumor activity in preclinical models of prostate cancer.