MADRID—When patients reached Ambrx Biopharma’s phase 1/2 clinical trial for prostate cancer, they were nearing the end of their treatment journey. It’s hard to read that some had gone through 13 rounds of treatment before they entered the study.
CEO Daniel O’Connor and Chief Clinical Officer Sandra Aung don’t take that lightly.
“They're last line patients, they have no other options and typically patients in that bucket go for clinical trials,” Aung said on the sidelines of the European Society for Medical Oncology Congress in Madrid.
Ambrx wants to provide another option, but more importantly, a better option for these patients who are facing difficult decisions after a long fight with cancer. The company unveiled early-stage data from the APEX-01 study of the antibody-drug conjugate (ADC) ARX517 showing anti-cancer activity and few adverse events—none serious.
For efficacy, Ambrx reported that more than half of the 23 patients had a 50% or more reduction in prostate specific antigen, which is elevated in prostate cancer. Seventeen out of 21, or 81% of evaluable patients, also had a steep reduction in circulating tumor DNA. In a smaller analysis of six patients, half who had prior prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy, had more or equal to 50% reduction in prostate specific antigen. And out of four evaluable patients, half had a 30% or more reduction in target lesions.
There were no treatment-related serious adverse events or dose limiting toxicities, a discontinuation rate of just 3.1% and fewer than 10% grade 3 treatment related adverse events—but no grade 4 or 5s.
Aung said the safety data are particularly important for these late-stage patients: “We don’t want to make them sicker.”
“I don't know if I've ever seen a late-stage cancer drug, after two years of clinical development, not having an [serious adverse event]. Not one,” O’Connor said in an interview.
The grade 3 events were lymphocyte count decreases, platelet count decreases and one instance of left ventricular dysfunction, which Aung said was found in the course of the treatment and was not considered serious.
“We don't want to diminish what a grade 3 is, but on a grand scheme of things for this late-line patient on this drug, [it’s] very tolerable. We would feel very comfortable calling it strong safety,” Aung said.
While the data are from a small population, Ambrx is already forming a detailed strategy of next steps. Aung said that the safety profile resulted from the biotech’s careful testing and drug discovery process.
“It's very rare to find this kind of safety profile. It is really born from technology, it's not luck,” she said.
There’s still a lot to do in the clinic, including fully enrolling the study and conducting dose expansion, O’Connor said. With so few safety events, he thinks the dose can go higher to push efficacy even further.
“Ultimately, if we see a data plateau and we see an impact over efficacy, we'll make a decision probably not to move forward to a higher level,” O’Connor said. “It's incumbent on us to continue to explore higher doses to see if there's more efficacy.”
Ambrx also saw in the small dataset the possibility that the treatment will work regardless of a patient’s PSMA biomarker levels, which would mean ARX517 could have access to a wide patient population. The trial did not screen for PSMA, so the patients had a mix of high and low levels.
“If we don't have to have a biomarker program, we do not want to have one,” O’Connor said.
Aung said they are certainly going to collect that data, but the goal is not to pick one population over the other.
“We want to be able to treat patients, not have to select them,” she added. “We're going to collect it and we're going to look at the data and make a decision on whether it's necessary or not.”
Ambrx's scorecard
The ESMO presentation represents a major reset for Ambrx. Almost a year to the day, the biotech laid off 15% of its staff and trimmed the pipeline down to ARX517 and a couple other early-stage assets. The dramatic moves came after a breast cancer program fell apart.
“Focus is really the key for us. And I think frankly, we’re really pleased with the progress the company has made this year,” said O’Connor, who took the helm in November 2022 after the layoffs. “There was a reduction that happened last fall. A year later, there's really kind of a complete change. A reset.”
Aung is another fresh face, having taken on her role in February.
Ambrx has also managed to raise some cash and extend its runway to 2026, all in a market O’Connor admits is challenging for the larger industry. The most recent offering in June closed with $75 million, which followed a $78 million raise in March.
Even the breast cancer program, initially the cause of the company cutbacks, is returning. In March, Ambrx said that a phase 2 study in China conducted by partner NovoCodex Biopharmaceuticals showed that ARX788 demonstrated better progression-free survival than the control group. O’Connor moved to resurrect the drug.
“It was shelved not because of efficacy, it was shelved because the company was concerned about cash burn a year ago, just before I was the CEO,” O’Connor said. Ambrx always believed there was a signal in the data.
Now, he says Ambrx is conducting a small signal-finding study in a group of breast cancer patients who have no other options. The FDA had previously granted a fast-track tag for the treatment.
“On each scorecard, we feel like we've really changed the trajectory of the company. And we are really pleased with the progress,” O’Connor said.