Novartis is pushing deeper into antibody-drug conjugate (ADC) development, paying $1.1 billion upfront to buy Myricx Bio for a pipeline based on a novel payload.
Switzerland’s Novartis largely stayed on the sidelines as its peers plowed into the ADC space. Talking to investors in recent years, Novartis executives explained that they have internal ADC projects and keep tabs on external developments. But the company made targeted radioligand therapies (RLTs), not ADCs, the cornerstone of its oncology business.
Now, Novartis has found a platform compelling enough to get more actively involved in ADCs. Myricx, a London-based biotech, is developing ADCs that deliver N-myristoyltransferase inhibitor (NMTi) payloads.
The FDA has approved ADCs using a range of payloads. Drugs including AstraZeneca and Daiichi Sankyo’s Enhertu deliver topoisomerase I (TOPO-1) inhibitors, while ADCs such as Astellas and Pfizer’s Padcev use microtubule inhibitors. NMTis are a different approach that Novartis predicts could tackle resistance and other limitations of existing payloads, broadening the use of ADCs across multiple tumor types.
Myricx and its collaborators found NMTis selectively eliminate senescent cells, which can facilitate tumor progression. In solid cancer models, NMTi-ADCs aimed at HER2, TROP2 and B7-H3 matched (PDF) or beat the efficacy of TOPO-1 treatments aimed at the same targets.
The biotech picked the B7-H3 and HER2 ADCs as its lead candidates. Pursuing the targets puts Myricx in competition with multiple other ADCs, including approved assets. The FDA approved the HER2-directed ADC Enhertu in 2019, with AstraZeneca reporting (PDF) sales of $2.8 billion last year. Daiichi and Merck & Co.’s B7-H3-directed ADC ifinatamab deruxtecan is undergoing priority review at the FDA.
With rivals showing B7-H3 and HER2 are viable ADC targets, Myricx’s programs are partly derisked. The biotech knows ADCs against B7-H3 and HER2 can improve outcomes in solid tumor patients. The critical outstanding question is whether Myricx’s technology can improve on the incumbent drugs, potentially by treating TOPO-1-resistant patients or unlocking settings where existing payloads have limitations.
The B7-H3 and HER2 programs could serve as a proving ground for NMTis. If it clinically validates the technology, Novartis sees opportunities to establish NMTis as a new class of ADC payload for use across more targets and platforms. Up to $400 million in milestones are tied to the success of Myricx’s assets.
The acquisition aligns with comments Shiva Malek, Ph.D., global head, oncology disease area at Novartis Institutes for BioMedical Research, made at the company’s “meet the management” day in November. The pharma is focused on selectively delivering “biology-matched payloads” to tumors, Malek said at the time. Within that work, Novartis was considering where pan-cytotoxic ADCs may complement its work on RLTs.