AstraZeneca has joined the swarm of biotechs targeting Claudin18.2 (CLDN18.2). In return for $25 million upfront and more on the back end, the Big Pharma has landed worldwide rights to Harbour BioMed’s (HBM's) bispecific, positioning it to fight for a market targeted by Amgen, Astellas, BioNTech and more.
With research showing the tight junction molecule CLDN18.2 is expressed in 60% of gastric cancers as well as by other gastrointestinal tumors, biotechs are aiming an arsenal of monoclonal antibodies, cell therapies, bispecifics and mRNA candidates at the target. Multiple programs are already in the clinic, but AstraZeneca has nonetheless seen value in picking up a candidate that is further back in the pack.
AstraZeneca is paying $25 million upfront and committing up to $325 million in development, regulatory and commercial milestones to land the global rights to HBM7022, a bispecific antibody designed to hit CLDN18.2 and CD3. Once the deal closes, AstraZeneca will take responsibility for further development.
By binding to CLDN18.2 and CD3, the bispecific antibody could activate T cells and turn them against the tumor. HBM has designed the molecule to have high affinity for CLDN18.2 and low affinity for CD3, a decision intended to yield potent cytotoxicity while minimizing the risk of cytokine release syndrome.
According to HBM, the candidate has shown efficacy against Claudin18.2-positive gastric cancer, both in its wild type and mutated forms, and against pancreatic cancer. The evidence of efficacy comes from preclinical studies.
With HBM7022 yet to enter the clinic, AstraZeneca has joined the CLDN18.2 race some way behind the front runners. Astellas paid an initial 422 million euros ($459 million) to buy Ganymed Pharmaceuticals for its anti-CLDN18.2 antibody zolbetuximab in 2016. Having started a pair of phase 3 clinical trials in 2018, Astellas now has the primary completion of the studies in its sights. Since the start of the phase 3 trials, a raft of other drug developers have begun trialing different ways of engaging the target.
Amgen took a CLDN18.2 bispecific, AMG 910, into the clinic in 2020, although it stopped enrollment in the study late last year well short of its recruitment goal. BioNTech has aimed its mRNA technology at the target, entering the clinic in 2020. Legend Biotech, the company behind Johnson & Johnson’s BCMA cell therapy, has a CAR-T against the target in the clinic, as does its compatriot CARsgen Therapeutics. They are part of a crowd of Chinese biotechs and hospitals working on trials of CLDN18.2 candidates.