Daiichi Sankyo and Merck Expand Collaboration to Develop Novel DLL3-Targeting T-Cell Engager for Small Cell Lung Cancer
核心洞察
Daiichi Sankyo and Merck (搜索) have expanded their existing partnership to include MK-6070, an investigational DLL3 (搜索)-targeting T-cell engager, with Merck receiving $170 million upfront in the agreement.
MK-6070 targets delta-like ligand 3 (DLL3 (搜索)), which is highly expressed in small cell lung cancer (搜索) and neuroendocrine tumors (搜索), and has received FDA Orphan Drug Designation for SCLC treatment.
The companies plan to evaluate MK-6070 in combination with ifinatamab deruxtecan (I-DXd) in patients with small cell lung cancer (搜索), addressing an aggressive cancer with significant unmet treatment needs.
Daiichi Sankyo and Merck (搜索) have expanded their global collaboration to include MK-6070, an investigational delta-like ligand 3 (DLL3 (搜索)) targeting T-cell engager, building upon their existing partnership for antibody-drug conjugates. The companies announced on August 6, 2024, that they will jointly develop and commercialize the therapy worldwide, except in Japan where Merck will maintain exclusive rights.
Under the terms of the agreement, Merck (搜索) will receive an upfront cash payment of $170 million and has satisfied a contingent obligation from their original collaboration agreement. The companies will share research and development costs, commercialization expenses, and profits globally, with Merck handling manufacturing and supply responsibilities for MK-6070.
Targeting an Aggressive Cancer with High Unmet Need
Small cell lung cancer (搜索) (SCLC) represents an aggressive form of lung cancer with limited treatment options and poor survival rates. MK-6070 targets DLL3 (搜索), an inhibitory canonical Notch ligand that is highly expressed in SCLC and other neuroendocrine tumors (搜索) but minimally present in normal tissues, making it an attractive therapeutic target.
"Small cell lung cancer (搜索) is an aggressive, fast-growing form of lung cancer and new treatment approaches are urgently needed," said Dr. Dean Y. Li, president of Merck (搜索) Research Laboratories. "We are pleased to build upon our collaboration with Daiichi Sankyo and look forward to evaluating the novel combination of MK-6070 and ifinatamab deruxtecan in small cell lung cancer and other forms of cancer."
The investigational therapy is currently being evaluated in a Phase 1/2 clinical trial (NCT04471727) as a monotherapy in patients with advanced cancers expressing DLL3 (搜索) and in combination with atezolizumab in certain SCLC patients. The U.S. Food and Drug Administration granted Orphan Drug Designation to MK-6070 for SCLC treatment in March 2022.
Expanding a Strategic Oncology Partnership
This agreement builds upon the companies' October 2023 collaboration to jointly develop and commercialize three investigational DXd antibody-drug conjugates: patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd), and raludotatug deruxtecan (R-DXd).
"Expanding our oncology pipeline with a DLL3 (搜索) T-cell engager further supports Daiichi Sankyo's strategy to create new standards of care for patients with cancer worldwide," said Ken Takeshita, MD, global head of R&D at Daiichi Sankyo. "We look forward to continuing our relationship with Merck (搜索) with the addition of MK-6070 as it provides potential synergies with our established antibody-drug conjugate collaboration, particularly ifinatamab deruxtecan."
Novel Combination Approach
A key focus of the expanded collaboration will be evaluating MK-6070 in combination with ifinatamab deruxtecan (I-DXd) in patients with SCLC. This combination approach could potentially offer new treatment options for patients with limited therapeutic alternatives.
MK-6070 is a tri-specific T-cell engager that Merck (搜索) obtained through its acquisition of Harpoon Therapeutics. The therapy works by engaging the immune system's T cells to target cancer cells expressing DLL3 (搜索), which is found at high levels in SCLC and other neuroendocrine tumors (搜索) including melanoma (搜索), small cell bladder cancer (搜索), and metastatic castration-resistant prostate cancer.
Potential for Broader Applications
Beyond SCLC, the companies are exploring MK-6070's potential in other cancers where DLL3 (搜索) is expressed. The target's minimal expression in normal tissues makes it a promising candidate for selective cancer therapy with potentially reduced off-target effects.
The collaboration reflects both companies' commitment to developing innovative cancer treatments and leveraging complementary expertise. While the companies will share development and commercialization responsibilities globally, Merck (搜索) will maintain exclusive rights in Japan, with Daiichi Sankyo receiving royalties based on sales in that market.
R&D expenses specifically related to combining MK-6070 with ifinatamab deruxtecan will follow the structure established in the original agreement for ifinatamab deruxtecan, with Merck (搜索) generally recording worldwide sales for MK-6070.