Ambrx Provides Safety and Efficacy Data from Ongoing Phase 1/2 APEX-01 Trial of ARX517 in mCRPC at ESMO Congress

Newly published abstract regarding dose escalation patients provides key updates including:

• ≥50% PSA reduction observed across putative therapeutic dose levels ≥2.0 mg/kg – 3 of 3 in Cohort 6 (2.0 mg/kg), 2 of 3 in Cohort 7 (2.4 mg/kg) and 2 of 3 in Cohort 8 (2.88 mg/kg)
  
  
  
  
• No drug-related severe adverse events (SAEs) and no dose limiting toxicities (DLTs) observed in any cohort
  
  
  
  
• Pharmacokinetic (PK) data indicated strong ADC stability preventing premature release of anticancer payload
  
  
  
  
• Ambrx to host a live event / webcast to discuss additional data presented at ESMO on Sunday, October 22, 2023, at 8 p.m. CEST / 2 p.m. ET
  
  

SAN DIEGO, Oct. 16, 2023 (GLOBE NEWSWIRE) -- Ambrx Biopharma, Inc., or Ambrx, (NASDAQ: AMAM), today announced that two abstracts detailing updated safety and efficacy data from the ongoing Phase 1/2 trial, APEX-01 (), evaluating ARX517 for metastatic castration-resistant prostate cancer (mCRPC) were made available as part of the 2023 European Society of Medical Oncology (ESMO) Congress 2023 meeting, taking place in Madrid, Spain, October 20-24, 2023.

APEX-01 opened for enrollment in July 2021, and is the only ongoing clinical trial in the United States targeting PSMA with an antibody-drug conjugate (ADC). APEX-01 is a first-in-human, open-label, dose escalation and dose expansion study enrolling patients with mCRPC whose tumors have progressed on at least two prior FDA-approved treatments, including at least one second-generation androgen receptor pathway inhibitor. The inclusion criteria included one of the following: PSA progression defined by a minimum of two rising PSA values, radiographic progression by RECIST v1.1 or disease progression by the presence of new bone lesions.

The two clinical abstracts submitted to ESMO regarding the APEX-01 trial used a cutoff date of May 3, 2023. Ambrx will provide more mature data with a later data cutoff date, including a significantly greater number of patients from the dose expansion portion of APEX-01, in the ESMO posters and in its associated press release.

Ambrx will be hosting a Key Opinion Leader event at ESMO to discuss the data from these abstracts and posters, which will be live webcast on Sunday, October 22, 2023, at 8 p.m. CEST / 2 p.m. ET. Details regarding this event can be found on Ambrx’s website via this link .

Title: APEX-01: First-in-human Phase 1/2 study of ARX517, an anti-prostate-specific membrane antigen (PSMA) antibody-drug conjugate (ADC), in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

Abstract Highlights:

• In dose escalation patients treated via intravenous infusion every 3 weeks at putative therapeutic doses ≥2.0 mg/kg (Cohort 6 at 2.0 mg/kg, Cohort 7 at 2.4 mg/kg and Cohort 8 at 2.88 mg/kg):
  • 7 out of 9 patients experienced a ≥50% PSA reduction
    • 3 out of 3 patients in Cohort 6
    • 2 out of 3 patients in Cohort 7
    • 2 out of 3 patients in Cohort 8
  • 5 out of 5 patients experienced a ≥50% ctDNA reduction
    • 3 out of 3 patients in Cohorts 6
    • 2 out of 2 patients in Cohort 7
    • Cohort 8 data not available
• In 24 dose escalation patients treated from 0.32 mg/kg (Cohort 1) to 2.88 mg/kg (Cohort 8) ARX517 was well-tolerated at all doses
  • No treatment-related SAEs observed
  • No DLTs observed
  • Four Grade 3 treatment-related adverse events (TRAEs) were reported in Cohort 5 (1.7 mg/kg), Cohort 7 (2.4 mg/kg) and Cohort 8 (2.88 mg/kg) (two cases of lymphopenia, two cases of platelet count decrease)
    
    

Title: ARX517, a next generation anti-PSMA antibody drug conjugate (ADC), demonstrates notable stability and pharmacokinetic (PK) profile in the ARX517 Phase 1/2 clinical trial (APEX-01)

Abstract Highlights:

• The pharmacokinetics population consisted of 21 dose escalation patients having received ARX517 across all dose levels (0.32 to 2.4 mg/kg):
  • ARX517 exhibited virtually overlapping total antibody and ADC PK concentration-time curves at all dose levels tested indicating strong stability of the ADC with minimal premature payload release
  • A long ADC terminal half-life of ~6–10 days was observed at doses ≥ 1.4 mg/kg, thereby maximizing drug exposure over a dosing cycle of 3 weeks
  • Low concentrations of pAF-AS269 (approximately 0.02–0.2 ng/mL) were observed at all dose levels and appeared slowly in the circulation, with Cmax observed approximately 7 days after administration

“Based on the encouraging preliminary efficacy and safety results observed in the APEX-01 trial, we believe ARX517 has the potential to overcome the instability and resulting toxicity challenges of previous PSMA-targeted ADCs and may hold promise as a novel treatment modality for patients with mCRPC,” said Daniel J. O’Connor, Chief Executive Officer of Ambrx. “We look forward to sharing more results from the trial at the ESMO conference, which will include additional data from dose expansion cohorts.”

The full abstracts are available on the Company’s website via this .

Details of the poster presentations are as follows:

Session Title: Prostate Cancer Poster Session

Title: APEX-01: First-in-human phase 1/2 study of ARX517, an anti- prostate-specific membrane antigen (PSMA) antibody-drug conjugate (ADC), in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

Presenting Author: John Shen, M.D.

Date/Time: Sunday, October 22, 2023, from 12:00 – 13:00 CEST.

Session Title: Prostate Cancer Poster Session

Title: ARX517, a next generation anti-PSMA antibody drug conjugate (ADC), demonstrates notable stability and pharmacokinetic (PK) profile in the ARX517 phase 1 clinical trial (APEX-01)

Presenting Author: Scott T. Tagawa, M.D., M.S., FACP, FASCO

Date/Time: Sunday, October 22, 2023, from 12:00 – 13:00 CEST.

Session Title: Basic Science Poster Session

Title: Evaluation of ARX517, a next-generation anti-PSMA antibody drug conjugate for prostate cancer treatment, in preclinical enzalutamide-resistant and enzalutamide-sensitive pharmacology models and in toxicology models

Presenting Author: Shawn Zhang, Ph.D.,

Date/Time: Sunday, October 22, 2023, from 12:00 – 13:00 CEST.

Session Title: Basic Science Poster Session

Title: Preclinical characterization of ARX305, a next-generation anti-CD70 antibody drug conjugate for the treatment of CD70-expressing cancers

Presenting Author: David Mills, Ph.D.,

Date/Time: Sunday, October 22, 2023, from 12:00 – 13:00 CEST.

Ambrx APEX-01 ARX517 Webcast Information

to register and attend Ambrx’s KOL Event discussing additional ARX517 data presented at ESMO and showcasing presentations from prostate cancer experts, or visit .

About ARX517

ARX517 is an investigational antibody-drug conjugate composed of a humanized anti-PSMA mAb linked to AS269, an Ambrx proprietary potent microtubule inhibitor. ARX517 is designed to target the prostate-specific membrane antigen (PSMA). PSMA is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and has been validated as a therapeutic target.

In preclinical studies, the cancer cell killing payload of ARX517, pAF-AS269, is highly cytotoxic when delivered by a mAb into cancer cells. ARX517’s site-specific linkage, stable conjugation chemistry, and non-cleavable linker result in an ADC with a homogenous drug-antibody-ratio, mAb-like biophysical properties, and exceptional stability. Therefore, Ambrx believes ARX517 can promote highly specific tumor cell killing with minimal off-target toxicity.

ARX517 has the potential to be a first- and best-in-class anti-PSMA ADC addressing the high unmet medical need in mCRPC.

About APEX-01

Ambrx is currently investigating ARX517 in the APEX-01 (NCT04662580) first-in-human Phase 1/2, 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 (mCRPC) whose tumors have progressed following at least two FDA approved treatments for prostate cancer, including at least one second-generation androgen receptor pathway inhibitor, 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.

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 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 was 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 Ambrx routinely posts information that may be important to investors on its 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. 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: 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 Current Report on Form 8-K filed with the SEC on October 12, 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

MEDIA

Karissa Cross, Ph.D.

LifeSci Communications

615-651-4622

Source: Ambrx Biopharma, Inc.