Novartis has struck a deal worth up to $745 million with Ratio Therapeutics for a radiopharmaceutical that could help defend its franchise from would-be challengers including Bristol Myers Squibb and Eli Lilly.
Ratio, which shared details of the deal Monday, will work with Novartis on preclinical development of a radiotherapeutic candidate that targets somatostatin receptor 2 (SSTR2). Once Novartis has selected a candidate, the Swiss drugmaker will take over and handle all remaining development, manufacturing and commercialization activities.
The deal features an upfront fee of undisclosed size and could be worth $745 million, plus royalties, once all milestones are factored in. The outlay has secured Novartis a new candidate in an area where it faces potential threats from rival radiopharmaceuticals that are in clinical development.
Novartis’ radiopharmaceutical Lutathera, first approved in 2018, has a targeting compound that binds to SSTR2. The receptor is overexpressed by gastroenteropancreatic neuroendocrine tumors, enabling companies to use SSTR2 to get radioactive isotopes to cancer cells while minimizing damage to healthy tissues. Lutathera generated $534 million over the first nine months of 2024, representing an increase of 17% over the same period last year.
However, most patients who receive Lutathera progress and then have limited treatment options. The situation has fueled interest in developing more effective alternatives to Lutathera, options for patients who relapse on Novartis’ drug and programs that expand SSTR2 medicines into new indications.
BMS and Lilly acquired SSTR2 radiopharmaceuticals in the takeovers of RayzeBio and Point Biopharma, respectively. Perspective Therapeutics also has a SSTR2 radiopharma drug candidate in development. Lutathera and Lilly’s PNT2003 use the beta-emitter lutetium-177 as their payloads. BMS and Perspective use different payloads, respectively selecting the alpha-emitters actinium-225 and lead-212.
Ratio’s press release makes no mention of the choice of payload for the Novartis project. The biotech’s in-house pipeline includes lutetium-177 and actinium-225 payloads, although the latter is the focus of the company’s technology platforms. Actinium-225 emits more energy than beta therapies such as lutetium-177, potentially making it more effective at killing tumor cells.
The choice of radiation source is one way developers can differentiate their candidates. The targeting molecule and linker technology are important, too, and affect factors such as the uptake of the payload into the tumor and clearance of the isotope from normal tissues. Those factors influence efficacy, safety and tolerability and could determine which candidates make a mark on what could be a competitive market.
