8-K: Cullinan Therapeutics Secures Global Rights to Velinotamig, Bolstering Autoimmune Disease Pipeline with BCMAxCD3 T Cell Engager

Cullinan Therapeutics has entered into an exclusive global licensing agreement with Genrix Bio for velinotamig, a clinical-stage BCMAxCD3 bispecific T cell engager, expanding its focus on autoimmune diseases while maintaining its cash runway into 2028.

Summary

• Cullinan Therapeutics, Inc. (CGEM) has entered into an exclusive global (ex-Greater China) license agreement with Chongqing Genrix Biopharmaceutical Co., Ltd. (Genrix) for velinotamig, a BCMAxCD3 bispecific T cell engager.
• Cullinan will develop and commercialize velinotamig in all fields of use, specifically targeting autoimmune diseases, building on its prior efficacy in relapsed/refractory multiple myeloma (MM).
• Under the terms, Cullinan will pay Genrix an upfront license fee of $20 million upon signing.
• Genrix is eligible to receive up to $292 million in development and regulatory milestone payments.
• Genrix is also eligible for up to an additional $400 million in net sales-based milestones.
• Tiered royalties ranging from mid-single digit to mid-teens will be paid to Genrix on net sales of licensed products.
• Velinoamig has demonstrated potential best-in-class efficacy in Phase 2 studies for r/r MM, with an 85.4% Overall Response Rate (ORR) in 48 patients at the target dose.
• The drug showed a 79.2% ORR in patients with extramedullary disease (EMD), a poor prognosis subset of MM, which comprised 50% of the study population.
• Genrix Bio plans to initiate a Phase 1 study of velinotamig in autoimmune diseases in China by the end of 2024, with Cullinan intending to leverage this data to accelerate global clinical development.
• Cullinan reiterates its existing guidance to have cash resources into 2028, attributed to the refinement of its oncology pipeline.
• Velinoamig received Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) for the treatment of relapsed and refractory multiple myeloma in China.

Sentiment

Score: 9

Explanation: The announcement is highly positive, indicating a strategic expansion into a promising therapeutic area with a strong clinical asset, while maintaining financial stability. The efficacy data presented for velinotamig is compelling, suggesting significant potential.

Positives

• The licensing agreement significantly expands Cullinan's pipeline in autoimmune diseases with a clinical-stage asset, velinotamig, complementing its existing CLN-978 program.
• Velinoamig has demonstrated strong efficacy data in relapsed/refractory multiple myeloma, including a high Overall Response Rate (85.4%) and notable efficacy in extramedullary disease (79.2% ORR), suggesting potential for best-in-class in its target class.
• The deal leverages Cullinan's core expertise in T cell engagers and its established network of investigators and key opinion leaders (KOLs) in autoimmune diseases.
• The agreement is structured to maintain Cullinan's cash runway into 2028, indicating financial prudence despite the upfront payment and potential future milestones.
• Genrix Bio's planned Phase 1 study in China for autoimmune diseases is expected to accelerate global clinical development for Cullinan, providing valuable initial data.
• The addition of a BCMAxCD3 bispecific T cell engager (plasma cell depleter) allows Cullinan to pursue comprehensive B cell and plasma cell depletion, addressing a broader range of autoimmune diseases.

Negatives

• The agreement involves substantial potential future milestone payments totaling up to $692 million, plus tiered royalties, which could represent significant financial obligations if velinotamig is successful.
• While efficacy data is positive, the safety profile in multiple myeloma included high rates of certain adverse events such as infection (81.3% any grade, 50.0% Grade 3) and neutropenia (89.6% any grade, 64.6% Grade 3), which will require careful management in autoimmune indications.

Risks

• Uncertainty regarding the timing and results of regulatory submissions for velinotamig in autoimmune diseases.
• The success of clinical trials and preclinical studies for velinotamig is not guaranteed, and results may not be predictive of future outcomes.
• Risks related to Cullinan's ability to protect and maintain its intellectual property position for velinotamig.
• Potential risks related to manufacturing, supply, and distribution of velinotamig if it progresses to commercialization.
• The risk that velinotamig, or any other product candidate, will not be successfully developed and commercialized.
• The effect of changes in global economic conditions, including uncertainties related to international trade policies, tariffs, and supply chain dynamics, on Cullinan's business and operations.
• The success of any collaboration, partnership, license, or similar agreements, including the one with Genrix Bio, is subject to various factors.

Future Outlook

Cullinan Therapeutics expects to accelerate the global clinical development of velinotamig in autoimmune diseases by leveraging data from Genrix Bio's planned Phase 1 study in China. The company aims to execute parallel development for both CLN-978 and velinotamig across B-cell and plasma cell mediated autoimmune diseases. Cullinan reiterates its guidance for cash resources to extend into 2028, supported by its current operating plan and refinement of its oncology pipeline.

Management Comments

• Nadim Ahmed, CEO of Cullinan Therapeutics, stated: "We believe T cell engagers represent the next wave of innovation in autoimmune diseases, and we are excited to build upon our core T cell engager expertise and extensive KOL relationships to develop another potential best-in-class, clinical-stage program."
• Ahmed also commented: "Adding a BCMAxCD3 bispecific T cell engager to our pipeline complements our rapid global clinical development of CLN-978, enabling us to address the needs of more patients across a broader range of autoimmune diseases than with either molecule alone."
• Dr. Liu Zhigang, Chairman, CEO, and CSO of Genrix Biopharmaceutical, remarked: "With our planned Phase 1 study of velinotamig in autoimmune diseases, we will be able to quickly leverage our experience in autoimmune diseases to complete the study in China expeditiously."
• Dr. Zhigang added: "Cullinan is a proven leader in developing T cell engagers and we are confident in the company's ability to carry the program forward to address the needs of patients with autoimmune diseases."

Industry Context

This licensing agreement positions Cullinan Therapeutics as a significant player in the evolving landscape of autoimmune disease treatment, particularly in the T cell engager (TCE) space. By acquiring velinotamig, a BCMAxCD3 bispecific TCE, Cullinan is expanding beyond its CD19 TCE (CLN-978) to target both B cells and long-lived plasma cells, which are crucial in the pathogenesis of various autoimmune conditions. This dual approach aligns with a growing industry trend towards more precise and potentially disease-modifying therapies for autoimmune diseases, moving beyond broad immunosuppression. The focus on BCMA, a validated target in multiple myeloma, for autoimmune indications represents an innovative application of established oncology mechanisms.

Comparison to Industry Standards

• Velinoamig demonstrated a higher Overall Response Rate (ORR) of 85.4% in relapsed/refractory multiple myeloma patients (n=48) compared to approved BCMA TCEs like Elranatamab (57.7%, n=97), Teclistamab (61.8%, n=110), and Linvoseltamab (70.9%, n=117).
• Velinoamig showed a significantly higher ORR in patients with extramedullary disease (EMD) at 79.2%, compared to Elranatamab (36.4%), Teclistamab (35.7%), and Linvoseltamab (52.6%), despite having a larger proportion of EMD patients in its study (50.0% vs. 16.2%-34.0%).
• The Complete Response (CR) rate for velinotamig was 33.3%, which is similar to Teclistamab (28.2%) and Elranatamab (25.8%), but lower than Linvoseltamab (49.6%).
• The Very Good Partial Response (VGPR) rate for velinotamig was 66.7%, which is higher than Elranatamab (51.5%), Teclistamab (57.3%), and Linvoseltamab (63.2%).
• Velinoamig's MRD-neg rate was 39.6%, higher than Teclistamab's 26.7% (MRD-neg rates for Elranatamab and Linvoseltamab were not provided for comparison in the document).

Stakeholder Impact

• Shareholders: Potential for increased company valuation and future revenue streams due to pipeline expansion and promising asset.
• Patients: Potential for new, highly effective treatment options for a broader range of autoimmune diseases.
• Employees: Continued and expanded opportunities in research, development, and clinical operations.
• Creditors: Maintained cash runway into 2028 suggests stable financial health, potentially reassuring creditors.

Next Steps

• Rapid initiation of global regulatory and clinical development plans for velinotamig.
• Execute parallel development for CLN-978 and velinotamig across both B-cell and plasma cell mediated autoimmune diseases.
• Genrix Bio to initiate a Phase 1 study of velinotamig in autoimmune diseases in China later in 2024.
• Activate existing autoimmune investigator and KOL network for clinical development of velinotamig.
• Prepare for global regulatory interactions regarding velinotamig.

Key Dates

Recommendation

Keywords

Cullinan Therapeutics, Genrix Bio, velinotamig, BCMAxCD3, bispecific T cell engager, autoimmune diseases, multiple myeloma, licensing agreement, biopharmaceutical, clinical-stage, drug development, BCMA, CD3, plasma cell depletion, CLN-978, TCE, biotech, pharmaceuticals