Ambrx cuts 15% of staff and dumps lead HER2 asset after 'strategic review'

Ambrx Biopharma has been mulling major changes since August. Now, it has confirmed what form these will take: narrowing its cancer pipeline to earlier-stage therapies and dumping its lead asset at the expense of 15% of its workforce.

Change has been afoot at the biotech since July, when the company revealed that a relaxin heart failure collaboration with Bristol Myers Squibb had hit the buffers. CEO Feng Tian, Ph.D., headed for the exit two months ago, when the company also unveiled a “strategic review” of its pipeline. The search for a CEO remains ongoing, the company said in a release yesterday.

Board member Kate Hermans is continuing to serve as CEO in an interim role and is overseeing the company’s new strategy.

It turns out that new strategy will see Ambrx dropping its phase 3 HER2 antibody-drug conjugate (ADC) dubbed ARX788. The company has hit pause on trials of the therapy and will seek a development partner for the drug outside of China, where NovoCodex already owns the rights.

With AstraZeneca and Daiichi Sankyo’s blockbuster Enhertu becoming the first approved therapy targeting patients with the HER2-low breast cancer subtype in August, Hermans referred in general terms to changes in the HER2 market as a reason for the strategic pivot.

“There has been a significant shift this past year in the HER2 metastatic breast cancer competitive landscape,” the interim CEO said in the release. “As a result of our assessment, the board has endorsed the decision that the company should pause the internal development of ARX788 and seek a partner to further its development ex-China in order to extend the cash runway into 2025.”

In its place, the phase 1 ADC therapy ARX517 will be promoted up to lead asset, Ambrx said. The company believes ARX517 has the potential to be the first ADC therapy to specifically target prostate-specific membrane antigen to treat prostate cancer. Safety data from the phase 1 study are due to read out in the second half of 2023. At that time, Ambrx can decide on a recommended dose and move into a phase 1b/2 trial.

The San Diego-based biotech also has two other assets that will continue in development. ARX305 is an anti-CD70 ADC that is due to begin phase 1 trials in the second half of next year, subject to results from a study sponsored by NovoCodex. The other asset is the smart PEG-IL2 called ARX102, for which the company plans to seek FDA permission in the first half of 2024 to start human trials, subject to results from a Sino Biopharm-sponsored trial in China.