Merck is set to expand its oncology pipeline through the acquisition of clinical-stage biotech Harpoon Therapeutics in a deal worth up to $680 million. The buyout will give Merck access to Harpoon’s novel T cell engagers, strengthening its position in the hotly contested cancer immunotherapy space.
Merck Goes on the Hunt for Novel Cancer Therapies
Merck has entered into a definitive agreement to acquire Harpoon Therapeutics, a clinical-stage immunotherapy company developing novel T cell engagers for the treatment of cancer. Under the terms of the agreement, Merck will acquire Harpoon for an upfront payment of $682 million in cash, with the potential for an additional $630 million in regulatory and commercial milestones [1].
The deal will expand Merck’s presence in the high-value area of T cell engagers, bispecific antibody constructs capable of bringing T cells and cancer cells into close proximity to elicit an anti-tumor immune response. Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform has generated three clinical-stage candidates for both solid tumors and hematologic malignancies [2].
“Harpoon has demonstrated excellence in developing T cell engagers with multiple clinical programs,” said Dr. Eliav Barr, Senior Vice President of Global Clinical Development at Merck Research Laboratories. “We believe Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform will complement our work in immuno-oncology.” [3]
The buyout gives Merck another foothold in the fiercely competitive T cell redirection space, currently dominated by Amgen’s Blincyto and Novartis’ recently approved T-Charge platform. But unlike existing approaches, Harpoon’s TriTAC technology does not require T cell co-stimulation or HLA matching, allowing for broader application across patient populations.
Harpoon Wields Novel T Cell Engagers Against Cancer
Founded in 2015, Harpoon Therapeutics leverages its proprietary TriTAC platform to develop novel T cell engagers, bispecific antibodies that bind both cancer antigens and T cell receptors. This brings cancer and immune cells into close contact, activating T cells to eliminate malignant cells [4].
The TriTACs have several advantages over traditional T cell engagers:
- Higher affinity and activity without need for T cell stimulation
- HLA-independence allows targeting of all patients
- Half-life extended to multiple days through albumin binding
- Small size enables tissue penetration
The platform has generated three clinical-stage TriTACs against both solid and liquid tumors:
- HPN217: Targeting BCMA in relapsed/refractory multiple myeloma
- HPN424: Targeting prostate-specific membrane antigen (PSMA) in metastatic castration-resistant prostate cancer (mCRPC)
- HPN536: Targeting mesothelin in ovarian and pancreatic carcinomas
An additional 6 preclinical programs are under development, positioning Harpoon as a leader in next-generation T cell engagers. The company has ongoing clinical collaborations with AbbVie and Genentech to explore combination regimens.
Harpoon’s experienced leadership team brings together expertise in oncology drug discovery, protein engineering, translational science and clinical development from companies like Aduro Biotech, Macrogenics and Genentech.
Merck Builds Leading Immuno-Oncology Franchise
The addition of Harpoon’s pipeline expands Merck’s presence in the high-growth cancer immunotherapy space, an area of intense focus for the pharmaceutical giant.
Merck already markets the PD-1 checkpoint inhibitor Keytruda, approved in over 25 indications across more than 17 tumor types. Keytruda hit nearly $17 billion in sales in 2023, making it the company’s top-selling product. But Merck faces stiff competition from rival checkpoint drugs like Bristol Myers’ Opdivo and Roche’s Tecentriq.
To consolidate leadership in immuno-oncology, Merck is aggressively in-licensing innovative platforms through deals like the $2.7 billion acquisition of cancer drug developer VelosBio in 2020 and partnerships with companies like Seagen, Kelun and Artiva Biotherapeutics [5].
The addition of Harpoon’s promising clinical pipeline and novel T cell activation technology complements these efforts, further cementing Merck’s dominance in cancer immunotherapy.
Outlook: Harpoon Deal Spearheads Merck’s Oncology Push
The Harpoon acquisition signals Merck’s intent to aggressively pursue new immuno-oncology combinations and treatment modalities. In a recent interview, Merck’s head of global clinical development highlighted T cell redirection as a major area of focus for expanding Keytruda’s reach and overcoming resistance mechanisms [6].
Harpoon’s bispecific T cell engagers could prove to be an ideal partner for Keytruda, recruiting and activating T cells at the tumor site to amplify its effects. Preclinical data already suggests combining TriTACs with PD-1 inhibition may overcome resistance in “cold” low T cell tumors. Clinical studies testing these combinations could begin swiftly given Merck and Harpoon’s shared focus on hematologic malignancies and lung cancer.
The deal also expands Merck’s pipeline of T cell engagers, pitting them more directly against rivals Amgen and Novartis. Harpoon’s candidates boast differentiated properties that could carve out market share against Blincyto and T-Charge, although clinical data remains early stage.
If successful, Harpoon’s treatments could reshape standards-of-care for blood cancers like multiple myeloma and drive expansion into new solid tumor settings. But clinical development carries substantial risk given the platform’s novel approach.
Ultimately, the Harpoon buyout offers Merck the chance to spear cancer from another angle, further cementing its immunotherapy leadership amid fierce competition. But the deal’s success will hinge on progress in the clinic – where cancer’s complexity continues to test the limits of even our sharpest weapons.
References
- Merck to Acquire Harpoon Therapeutics
- Merck Close to Harpoon Buyout
- Merck Diversifies Oncology Pipeline
- Merck Advances Harpoon Buyout Talks
- Merck to Buy Harpoon for $680 Million
- Harpoon Buy to Expand Keytruda
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