For years, as Big Pharma poured billions into antibody-drug conjugates, Novartis CEO Vas Narasimhan notably stayed on the sidelines. Speaking at the J.P. Morgan Healthcare Conference two years ago, the helmsman pointed to Novartis’ deep commitment to radioligand therapy as its primary targeted cancer delivery platform.
That long holdout is finally coming to an end as Novartis agreed to acquire London-based biotech Myricx Bio for up to $1.5 billion. The deal includes $1.1 billion upfront for a little-known biotech with no clinical data.
Asked by Fierce during Novartis’ second-quarter earnings call what prompted the apparent shift in strategy, Narasimhan said that while the company’s commitment to radiopharmaceuticals “remains completely unchanged,” the evolving oncology landscape called for a complementary approach.
“We know that there are certain cancer types that […] could be better served by ADCs, or served in different ways than they could be by RLTs,” Narasimhan explained on the call.
“We’ve been looking for years for a novel approach to ADCs, knowing that it’s a competitive space,” he continued. “I think we were looking for that differentiated entry point, and Myricx provided us that.”
As Narasimhan noted, the ADC field is crowded with companies developing payloads based on topoisomerase 1 inhibitors, which disrupt DNA replication, or tubulin inhibitors such as MMAE, which trap cancer cells in the division phase and cause them to self-destruct. AstraZeneca and Daiichi Sankyo’s Enhertu is a prominent example of the first approach, while Astellas and Pfizer’s Padcev falls into the second category.
However, toxicity and treatment interruptions, resistance and narrow therapeutic windows have hampered those mechanisms from achieving their full therapeutic potential.
Myricx’s platform instead targets N-myristoyltransferase (NMT), an enzyme crucial to protein stability and, therefore, cancer cell survival. Because it does not rely on the two pathways used by existing ADC payloads, the platform could theoretically overcome resistance to those treatments.
Spun out of Imperial College London and the Francis Crick Institute, Myricx built on earlier malaria research to develop the know-how to selectively target NMT in diseased cells while sparing normal human cells. That selectivity could give Myricx’s payload what Narasimhan described as a cleaner, differentiated safety profile.
According to Novartis, preclinical data suggest this novel NMTi payload “may have broad activity across solid tumors, including TOPO-1 resistant models, and may enable more effective use of ADCs in settings where existing payload classes have limitations.”
Myricx’s lead candidates target B7-H3 and HER2, two of the hottest targets in ADC development, and have generated preclinical data.
“Assuming the payload proves itself to be attractive from a safety standpoint, we would certainly look to expand that NMTi payload across more delivery vehicles and more drug targets, and see how we could expand from there,” Narasimhan said.
As for whether Myricx is a harbinger of more ADC deals for Novartis, the chief executive said, “Nothing that’s immediately on our minds. Right now, our focus will be to try to maximize the Myricx technology to the extent the science allows us to.”
The Myricx deal follows a broader trend of biopharma companies seeking next-generation payloads.
In a recent interview with Fierce, Daiichi’s new R&D chief John Tsai, M.D.—formerly the chief medical officer of none other than Novartis—said developing novel payloads is a major focus for the Japanese ADC giant. These include a STING agonist payload that leverages the immune system rather than directly killing cells in a cytotoxic way.
On the dealmaking front, Roche recently put down $20 million upfront to tap into C4 Therapeutics’ degrader-antibody conjugate (DAC) capabilities, which use targeted protein degraders rather than cytotoxic chemotherapies as payloads. Similarly, Johnson & Johnson is shelling out $1 billion upfront to purchase DAC player Firefly Bio.
In another small acquisition, Eli Lilly recently bought ADC biotech CrossBridge Bio, which has a preclinical dual-payload candidate combining two inhibitors against TOP1 and ATR, which acts as a repair mechanism to save cells damaged by TOP1 inhibition.