After parting ways with BeiGene in 2023, Novartis effectively bowed out of the PD-1 race. Now, the rising class of bispecifics opened up an opportunity for the Swiss pharma to reenter the space from a new angle. The question is: Will the company take it?
“We’re certainly watching the space,” Novartis CEO Vas Narasimhan, M.D., said of PD-1xVEGF bispecifics during a fourth-quarter earnings call with reporters this morning.
“I think there were very interesting data that came out of China and then later in Europe, but I think we’re still waiting to see how that data matures before deciding is this something that we want to pursue,” Narasimhan said in response to a question from Fierce.
In September, Akeso presented strong phase 3 head-to-head data showing that its Summit Therapeutics-partnered PD-1xVEGF bispecific ivonescimab outperformed Merck & Co.’s Keytruda on progression-free survival in Chinese patients with previously untreated, PD-L1-positive non-small cell lung cancer.
While trying to brush off the threat by cautioning that a statistically significant overall survival showing may be hard to achieve, Merck soon got a PD-1xVEGF bispecific for itself, paying $588 million upfront—with up to $2.7 billion in milestones—for rights to LaNova Medicines’ candidate LM-299.
Almost simultaneously, BioNTech unveiled a plan to acquire its partner Biotheus to gain full control over their PD-L1xVEGF bispecific candidate, BNT327. BioNTech shared promising early-phase data for BNT327 in December, which Leerink Partners analysts argued “has potential to usurp and extend [Keytruda] as the backbone checkpoint in 1L triple-negative breast cancer.”
Novartis once showed an interest in PD-1 but left the space by ending its collaboration with BeiGene on the PD-1 inhibitor Tevimbra after significant regulatory delay and changing FDA stance in the U.S. At that time, Novartis cited a changing PD-1 inhibitor landscape, basically indicating that the space had become too crowded for yet another similar drug.
Novartis didn’t have the best experience with bispecifics in oncology. The company paid Xencor $150 million upfront in 2016 to co-develop two CD3 T-cell engaging bispecifics, only to have dropped both programs by 2021.
But the Swiss pharma in July 2024 renewed its hope in the modality, putting down $150 million upfront to work with Dren Bio on bispecifics for cancer.
As Narasimhan noted, Novartis have a number of efforts ongoing in bispecifics, primarily in immunology. These include T-cell engagers being developed for systemic lupus erythematosus and bispecific antibodies for atopic dermatitis, all in phase 1 development with readouts not expected until 2027 at the earliest, according to a January presentation.
“Our thinking is, can we develop a medicine that’s better than the current standard of care in atopic dermatitis and in some of the relevant indications,” Narasimhan said on Friday’s call.
“We’ll have more data in the coming years to guide us on how those will progress,” he added.
As to oncology, Novartis’ primary focus is radioligand therapies, plus “a smaller effort on antibody-drug conjugates,” Narasimhan noted.
In radioligand therapies, Novartis is waiting to hear back from the FDA on its application for PSMA-targeted Pluvicto in pre-taxane metastatic castration-resistant prostate cancer. After an early progression-free survival win, Novartis delayed its filing for more than year until the overall survival data from the phase 3 PSMAfore trial turned in favor of Pluvicto.
The company also didn’t use a priority review voucher as the FDA requested the flexibility to review the final overall survival result. Friday, Novartis disclosed that the final analysis remained in Pluvicto’s favor without adjusting for patient crossovers.
Novartis has multiple pipeline candidates in radiopharmaceuticals and last year doubled down on the field with the $1 billion upfront acquisition of Mariana Oncology, with a lead program targeting DLL3, plus a licensing deal with Ratio Therapeutics to develop a somatostatin receptor 2 (SSTR2)-targeting candidate.