AstraZeneca is doubling down on the hot cancer target Claudin18.2, paying KYM Biosciences $63 million upfront for the global rights to an early-phase antibody-drug conjugate (ADC). The deal comes 10 months after the Big Pharma entered the space by paying $25 million upfront for a bispecific antibody.
Drug developers including Amgen, Astellas, BioNTech and Legend Biotech have thrown the full spectrum of biologic modalities at Claudin18.2 in the belief targeting the tight junction molecule can tackle tumors in the gastrointestinal tract. AstraZeneca joined the race in April 2022 when it paid Harbour BioMed $25 million, plus up to $325 million in milestones, for global rights to a CLDN18.2xCD3 bispecific antibody.
Now, the Anglo-Swedish drug developer has written another check for an asset that comes at the target from a different angle. AstraZeneca’s deal with KYM, a joint venture between Hong Kong-listed biotechs Keymed Biosciences and Lepu Biopharma, features up to $1.1 billion in milestones.
The outlay will give AstraZeneca control of CMG901, an ADC that uses a Claudin18.2-specific antibody to deliver the toxic payload monomethyl auristatin E to cancer cells. KYM has received IND clearance in China and the U.S., an achievement Keymed claims (PDF) is a first for a Claudin18.2-directed ADC, and has reached the dose-escalation stage of its phase 1 Chinese solid tumor trial.
Last month, Keymed reported (PDF) six responses to CMG901 in eight gastric cancer patients. The response rate was 100% in the three higher dose cohorts. Three people in the 27-subject safety cohort, which included pancreatic cancer patients, had drug-related grade 3 adverse events. Pharmacokinetic data showed that systemic exposure to the unconjugated toxic payload was low.
The early data have persuaded AstraZeneca to place a second bet on Claudin18.2. Both of AstraZeneca’s candidates are well behind the front-runner, Astellas. Late last year, a pair of phase 3 trials of Astellas’ anti-CLDN18.2 antibody zolbetuximab hit their endpoints, giving the Japanese company the data to seek approval and validating its decision to buy Ganymed Pharmaceuticals for $445 million upfront.
Astellas’ reign over the Claudin18.2 market could be short-lived. AstraZeneca, CARsgen Therapeutics and a pack of other organizations, including multiple Chinese biotechs and hospitals, are betting that better results can be achieved by applying modalities including ADCs, bispecific antibodies and cell therapies to the target.