#ASCO21: AbbVie-partnered Chinese biotech with first-in-class ambitions showcases early data on CD73 antibody
Weeks after Gilead-partnered Arcus whipped up some cheers from analysts around its small molecule CD73 inhibitor — presenting preliminary data at AACR that “exceeded expectations” — a Chinese biotech is unveiling its own early results using an antibody approach that it says puts more weight behind the target.
I-Mab touted a 23% objective response rate in the US Phase I dose escalation study, among 13 evaluable patients with several different types of advanced cancers. All were given a combination of uliledlimab and Roche’s PD-L1, Tecentriq.
While it’s still early, founder and chairman Jingwu Zang said the numbers mark “a very interesting starting point for us to build on.”
CD73, he said, has been on top of I-Mab’s target list as it hunts immuno-oncology agents that can help patients who don’t respond to checkpoint inhibitors. Others, including AstraZeneca and ORIC, are also pursuing it. Because it is part of the immunosuppressive adenosine pathway, blocking it is theorized to turn a cold tumor hot, thereby creating a better microenvironment for T cells to kill cancer.
The company’s claim to fame lies in the crowded CD47 field, where it boasts of a “differentiated” antibody that drew AbbVie in for a $3 billion pact. CD73 is nowhere nearly as popular — Zang counts only five antibodies around the world that’s reached clinical stage — but I-Mab similarly believes it has a unique drug on its hands.
In particular, investigators reported no “hook effect” in the Phase I trial, meaning the antibody potency seemed to increase proportionate with the dose rather than losing inhibition at a higher dose, an issue observed with certain other drugs in the class.
“This is not completely by design,” Zang said, explaining that they had only intended to avoid the epitopes targeted by others.
The resulting antibody appears safe and pleasantly surprised him with the clinical activity — both in PD-(L)1 treatment naïve and refractory cases. A patient with ovarian cancer achieved a complete response, two others saw a partial response, while another three had stable disease.
Interestingly, investigators noted that the three responders were also the only ones whose tumors had high expression of both CD73 and PD-L1 — biomarkers that I-Mab will likely start using to screen and stratify patients for future trials.
Zang noted that they will continue monitoring patients this trial (there are 20 in total), while also testing uliledlimab in a Chinese Phase II trial together with Junshi’s PD-1 Tuoyi, looking at non-small cell lung cancer as well as other metastatic cancers. Other combos are on the table.
Although he acknowledges that Arcus’ data — with the first cut suggesting a 41% ORR — look promising, Zang believes antibodies are better at providing the persistent and complete inhibition needed to shut down a target that’s expressed abundantly as CD73. The answers ultimately will have to come in future trials.
“We’re moving forward with full speed,” he said.
