AstraZeneca’s search for antibody-drug conjugates has again led to Asia. This time around, the Anglo-Swedish drugmaker is committing up to $55 million in upfront and near-term payments to secure global rights and join an intensifying race to offer options to patients who relapse after BCMA therapy.
The agreement sees AstraZeneca pay LaNova Medicines an upfront fee and sweeten the deal with up to $545 million in milestones to get its hands on the preclinical, GPRC5D-directed prospect LM-305. Inking the deal establishes AstraZeneca as a rival to Bristol Myers Squibb, Johnson & Johnson, Roche and other companies that see GPRC5D as a way to unlock the potentially lucrative post-BCMA patient population.
Those four pharma companies are part of a long list of drug developers that have thrown almost the full spectrum of modalities at BCMA in recent years, culminating in the approvals of BMS’ Abecma and J&J’s Carvykti. With their high response rates, those CAR-T cell therapies and other BCMA drugs look set to transform the treatment of multiple myeloma in the coming years. But with data suggesting most patients will eventually relapse, there is an unmet need for a later-line, post-BCMA treatment.
GPRC5D could be just that. Scientists have found the receptor in several myeloma cell lines and in bone marrow plasma cells from patients with the cancer. Otherwise, expression is limited to low levels in the skin and testes, suggesting drug developers can create therapies with minimal on-target, off-tumor effects.
AstraZeneca’s selection of ADC as the modality for going after GPRC5D sets it apart from the front-runners in the space, although the company has also ceded a head start to some rivals. BMS' anti-GPRC5D CAR-T therapy saw an 86% response rate in recipients during a small clinical trial, including responses in people previously treated with BCMA treatments. J&J and Roche have GPRC5D bispecifics in the clinic.
LaNova secured a green light to test LM-305 in humans in China late last year, putting it years behind the leading programs. But the complete responses and safety profile seen in tests in mice have persuaded AstraZeneca that the candidate has a shot at coming from behind and claiming a slice of the market.
The candidate slots into a growing portfolio of ADCs in development at AstraZeneca, which secured rights to HER2 ADC Enhertu and the TROP2-directed DS-1062 through partnerships with Daiichi Sankyo in 2019 and 2020 and recently paid KYM Biosciences for the global rights to a Claudin18.2 prospect.