Ambrx walked away from a breast cancer drug in October, citing the competitive pressure from AstraZeneca and Daiichi Sankyo’s blockbuster Enhertu. But new CEO Daniel O’Connor has spied an opportunity to get the drug back in the clinic.
Last week, the company held an investor day trumpeting the new path for the med, which will see a small new phase 2 trial in third-line HER2-positive breast cancer, after patients have progressed on Enhertu. Today, Ambrx is touting an interim analysis from a phase 3 trial conducted by partner NovoCodex Biopharmaceuticals where ARX788 demonstrated better progression-free survival than the control group. O’Connor said this early data supports the resurrection of the HER2 antibody-drug conjugate.
NovoCodex is testing ARX788 in the late-stage ACE-Breast-02 pivotal study in China, where the company holds the rights. The 441 patients in the trial have locally advanced or metastatic HER2-positive breast cancer and have previously received chemotherapy and Roche’s Herceptin.
ARX788 met the pre-specified interim primary endpoint by achieving greater progression-free survival compared to the control group, which received Novartis’ Tykerb and a chemotherapy. Ambrx did not detail the numbers, but said the result was statistically significant.
Ambrx ditched ARX788 as the lead asset back in October and vowed to find a partner to continue development outside of China. The move came with a 15% workforce reduction, too. But now, the therapy is back. The company held an investor day last week where O’Connor said the data that has emerged is too good to leave the therapy behind.
The CEO, who took the helm in November after the strategic review, detailed a new phase 2 trial of about 30 patients with breast cancer that has advanced on Enhertu, who have received no more than three prior lines of therapy. Enrollment is expected to take about 18 months.
O’Connor said that a big milestone for Ambrx this year will be “first patient, first dose” in the new study. He expects to be able to pick things back up where they left off after the company paused development in October. The hope is to amend the original study protocol from the ACE-Breast-03 trial, which Ambrx was conducting, and utilize studies that were already open to speed things along. That will allow Ambrx to “jump right back into those sites,” O’Connor said. The protocol amendment will take about three months to clear through the FDA, the CEO noted.
If the study shows a clinical signal of 20% to 30% objective response rate, ARX788 will be expanded into a registration-enabling trial.
The cost of this new study will be about $20 million to $30 million but O’Connor said the spend is justified by the potential upside value creation for shareholders. Since ARX788 kills cancer cells in a different way than Enhertu, there’s an opportunity to capture the 25% of patients who progress while taking Enhertu within the first 12 months, the CEO explained.