Ivonescimab

Oncology heavyweight Merck & Co. became the latest to throw its hat into the PD-1/VEGF bispecific antibody ring through a licensing deal with Chinese biotech LaNova Medicines. The agreement to develop LM-299 includes an upfront payment of $588 million, with LaNova eligible for further milestones of up to $2.7 billion."We continue to assemble a strong and diversified oncology pipeline spanning differentiated mechanisms and multiple modalities," remarked Dean Li, president of Merck Research Laboratories, with the company aiming to advance LM-299 "with speed and rigor."According to Merck, LM-299 has a differentiated molecular design, comprising an anti-VEGF antibody linked to two C-terminal single domain anti-PD-1 antibodies. A Phase I study for LM-299 kicked off in China last month, with LaNova noting at the time that an IND application in the US was planned to be filed by year-end.Summit leads raceThe space around bispecific antibodies targeting PD-(L)1/VEGF has been abuzz since Summit Therapeutics announced in May that its candidate, dubbed ivonescimab, improved progression-free survival over Merck's blockbuster PD-1 inhibitor Keytruda (pembrolizumab) in patients with PD-L1-positive, locally advanced or metastatic non–small-cell lung cancer. Results showed that ivonescimab reduced the risk of disease progression or death by 49% compared with Keytruda when used as a first-line treatment.With doctors keen to prescribe ivonescimab over Keytruda — according to recent findings from a FirstWord poll — Merck is looking to defend its oncology franchise. And it is not only Summit's effort the company needs to keep an eye on: yesterday, BioNTech agreed to spend $800 million upfront on Chinese biotech Biotheus, gaining the PD-L1/VEGF-A-targeting antibody BNT327, which is racing to registrational trials.For related analysis, see Vital Signs: BioNTech bags a bargain in a bubble for bispecifics.

Cancer drug dealmaking is heating up around promising candidates with the potential to top Merck by going after two targets versus the one addressed by the pharmaceutical giant’s blockbuster immunotherapy, Keytruda. Now Merck is joining in with a $588 million deal of its own. The agreement announced Thursday gives Merck global rights to LM-299, which has reached early clinical development under privately held LaNova Medicines. The Shanghai-based biotech could receive up to $2.7 billion in milestone payments depending on Merck’s progress with the drug across multiple indications. Merck’s Keytruda accounted for $21.6 billion in revenue in the first nine months of this year, a 17.6% increase compared to the same period in 2023. But Keytruda’s looming 2028 patent expiration has the pharma giant on the hunt for new drugs that can make up for the coming decline in sales for what has become the pharma giant’s top-selling product. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health Keytruda is monoclonal antibody designed to block PD-1, a checkpoint protein on immune cells. LaNova’s LM-299 is a bispecific antibody that blocks both PD-1 as well as VEGF, a protein that stimulates growth of blood vessels that support cancer growth. The promise of pairing of both of these mechanisms in a single drug shot to prominence in September with Summit Therapeutics’ report of data showing its bispecific drug, ivonescimab, topped Keytruda in a head-to-head clinical trial. In that China-only study, ivonescimab led to a 49% reduction in the risk of disease progression or death compared to Keytruda. This study was conducted by Summit’s partner, Akeso. Ivonescimab is already approved in China as a treatment for advanced cases of non-small cell lung cancer. Last month, LaNova announced the close of $42 million in financing to support clinical development of its pipeline, including LM-299. That drug’s Phase 1 test in China is enrolling patients with solid tumors. In preclinical research, LaNova has said the drug effectively blocked the PD-1 and VEGF signaling pathways. The company also said its tests indicate LM-299 has the potential for a better safety profile. Interest in bispecifics that target both PD-1 and VEGF drugs is growing. Crescent Biopharma’s bispecific candidate addressing those two targets is preclinical, but the company is piggybacking on the industry and investor attention to the drug class, recently striking a deal to go public in a reverse merger. On Wednesday, BioNTech announced it is paying $800 million up front to acquire partner Biotheus and its PD-L1/VEGF bispecific antibody, BNT327/PM8002. Last year, the German company secured global rights to the molecule outside of Greater China for $55 million up front. In addition to securing rights to the drug itself, the new deal enables BioNTech to expand its footprint with the addition of R&D and biologics manufacturing capabilities in China. BNT327/PM8002 has reached mid-stage studies in advanced cases of breast and lung cancers. The bispecific antibody is also in Phase 1/2 testing in combination with an antibody drug conjugate from BioNTech’s partnership with Duality Bio. Exclusive Heard at HLTH 2024: Insights from Innovative Healthcare Executives Executives from Imagine360, Verily, BrightInsight, Lantern, and Rhapsody shared their approaches to reducing healthcare costs and facilitating digital transformation. By MedCity News Merck has not disclosed its clinical trial plans for LM-299. In a prepared statement, Dean Li, president of Merck Research Laboratories, said the company is continuing to assemble an oncology pipeline spanning differentiated mechanisms and multiple modalities. Merck expects to close the acquisition of the LaNova drug by the end of this year.