Ratio Therapeutics, Inc.

Novartis CEO Vas Narasimhan, M.D., wants to see more mature data before deciding whether to venture into the PD-1xVEGF bispecific game in cancer.\n 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.

Novartis’ Kisqali (ribociclib) has been approved by the European Commission (EC) to reduce the risk of disease recurrence in a broad population of early breast cancer patients. The drug has been authorised for use in combination with an aromatase inhibitor as an adjuvant treatment for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer at high risk of recurrence. The regulator’s decision follows a recent recommendation from the European Medicines Agency’s human medicines committee and was based on positive results from the late-stage NATALEE trial, which included a broad patient population with HR-positive/HER2-negative stage 2 and 3 EBC, including those with node-negative disease. Adjuvant Kisqali plus endocrine therapy reduced the risk of disease recurrence by 25.1% compared to endocrine therapy alone, and demonstrated a consistent invasive disease-free survival benefit across all patient subgroups. Approximately 70% of breast cancer cases are diagnosed in the early stages of the disease and, despite current treatment options, those with HR-positive/HER2-negative stage 2 and 3 early breast cancer remain at risk of experiencing disease recurrence in the long term. Novartis’ Kisqali is designed to inhibit the CDK4/6 proteins which, when over-activated, can enable cancer cells to grow and divide too quickly, and is already approved in the EU for certain cases of advanced or metastatic breast cancer. Iris Zemzoum, president, Europe, Novartis, said: “Patients deserve access to treatment options that help minimise the risk of their cancer coming back and put their mind at ease. “We are proud of this approval, which will help to address a key unmet need and improve health outcomes for a broader population of patients in Europe.” The authorisation comes less than two weeks after Novartis entered into a worldwide licence and collaboration agreement worth $745m with Ratio Therapeutics to advance a somatostatin receptor 2-targeting radiotherapeutic candidate for cancer. The company also entered into a research collaboration and licence agreement worth over $2.4bn with Schrödinger earlier this month to identify and advance multiple drug candidates for it to develop and commercialise.

Novartis and Ratio Therapeutics’ have entered into a worldwide licence and collaboration agreement worth $745m to advance a somatostatin receptor 2 (SSTR2)-targeting radiotherapeutic candidate for cancer. The SSTR2 protein is expressed in many cancers, including neuroendocrine tumours, breast cancer, and head and neck carcinoma. The partners will work together on preclinical activities to research and select a development candidate, while Novartis will be responsible for all remaining development, manufacturing and commercialisation activities. The alliance will utilise Ratio’s technology platforms, which it says “enable the development of fit-for-purpose radiopharmaceuticals for therapy and imaging that possess pharmacokinetic modulation”. This approach improves drug availability, tumour delivery and tumour loading, according to Ration. In exchange, Ratio will receive combined upfront and potential milestone payments of up to $745m and will be eligible for tiered royalty payments. Fiona Marshall, president of biomedical research at Novartis, said: “Radioligand therapies hold transformative potential for certain forms of cancer… We are delighted to collaborate with Ratio to advance this… candidate and work together to bring forward additional therapeutic options for patients with difficult-to-treat cancer.” Also commenting on the agreement, Ratio’s chief executive officer, Jack Hoppin, said: “The team at Ratio is honoured and excited to partner with Novartis on the development of a next-generation SSTR2-targeting therapeutic. Together, we aim to develop a best-in-class therapy in the fight against SSTR2-expressing tumours.” The partnership comes shortly after Novartis and Schrödinger entered into a research collaboration and licence agreement worth over $2.4bn to advance multiple drug candidates for Novartis to develop and commercialise. The deal, announced earlier this month, will see the companies combine their existing research efforts to identify and advance drug candidates for undisclosed targets in Novartis’ core therapeutic areas. Novartis also expanded its peptide discovery collaboration with PeptiDream in May with a new agreement worth over $2.8bn, and entered into an exclusive licence agreement worth over $1bn in April for the development and commercialisation of Arvinas’ clinical-stage prostate cancer therapy.