Merck has entered into an agreement to acquire global rights to LM-299, an investigational anti-PD-1/VEGF bispecific antibody from LaNova Medicines, for an upfront payment of $588 million. The deal, announced on Thursday, includes potential milestone payments of up to $2.7 billion, depending on the drug's progress across multiple indications.
The acquisition underscores Merck's strategy to diversify its oncology pipeline as its blockbuster drug, Keytruda, faces patent expiration in 2028. Keytruda, a monoclonal antibody targeting PD-1, generated $21.6 billion in revenue in the first nine months of this year, marking a 17.6% increase compared to the same period in 2023. The company is actively seeking new therapies to offset the anticipated decline in Keytruda sales.
LM-299: A Bispecific Approach to Cancer Immunotherapy
LM-299 is a bispecific antibody designed to simultaneously block PD-1 and VEGF, a protein that stimulates blood vessel growth, which supports cancer progression. This dual-targeting approach has gained prominence recently, with Summit Therapeutics reporting that its bispecific drug, ivonescimab, outperformed Keytruda in a head-to-head clinical trial in China, demonstrating a 49% reduction in the risk of disease progression or death compared to Keytruda in first-line treatment of patients with PD-L1-positive advanced non-small cell lung cancer. Ivonescimab is already approved in China for advanced non-small cell lung cancer.
LaNova Medicines, a Shanghai-based biotech, recently closed a $42 million financing round to support the clinical development of LM-299 and other pipeline assets. LM-299 is currently in a Phase 1 clinical trial in China, enrolling patients with solid tumors. Preclinical research suggests that LM-299 effectively blocks both the PD-1 and VEGF signaling pathways and may offer a better safety profile compared to other agents.
Analyst Perspective
Leerink Partners analyst Daina Graybosch noted that Merck's acquisition of LM-299 validates the bispecific approach to targeting PD-1 and VEGF. She highlighted Merck's extensive experience in combining VEGF-targeting drugs with checkpoint inhibitors, referencing the company's partnership with Eisai on lenvatinib (Lenvima), a drug that blocks three VEGF receptors. The combination of Keytruda and Lenvima is approved for renal cell carcinoma and endometrial carcinoma. Graybosch suggests that Merck can leverage its prior experience to guide the development of LM-299, potentially overcoming challenges related to toxicity observed with previous VEGF-targeting agents.
"Of the failures, there is evidence to suggest toxicity and resulting treatment discontinuations from lenvatinib may have contributed to the efficacy failures, and we interpret Merck’s investment in LM-299 as a belief that improved toxicity observed with the bispecific class can overcome challenges with their first endeavor," Graybosch said.
Growing Interest in PD-1/VEGF Bispecifics
The deal underscores the increasing interest in bispecific antibodies that target both PD-1 and VEGF. Crescent Biopharma is also developing a bispecific candidate addressing these two targets and recently announced a reverse merger to go public. BioNTech recently acquired Biotheus and its PD-L1/VEGF bispecific antibody, BNT327/PM8002, for an upfront payment of $800 million. BNT327/PM8002 is currently in mid-stage studies for advanced breast and lung cancers and is also being evaluated in combination with an antibody-drug conjugate from BioNTech's partnership with Duality Bio.
Merck anticipates closing the acquisition of LM-299 by the end of this year. Dean Li, president of Merck Research Laboratories, stated that the company is committed to building an oncology pipeline with differentiated mechanisms and multiple modalities.
