PM-8002

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.

After initially promising more than $1 billion in biobucks to its partner Biotheus for a single drug, BioNTech is now buying out all of the China-based company for $800 million in cash and as much as $150 million more in milestones. In addition to the PD-L1/VEGF drug the companies were already partnered on, Wednesday’s deal will give BioNTech multiple clinical-stage drugs, an R&D hub, an operational biologics manufacturing site in China, and 300 employees. “We were looking for several years for the next-generation immune modulator. We believe we have found now the molecule that we were seeking,” CEO Uğur Şahin said in an interview with Endpoints News . The companies struck their initial partnership a year ago, built around BNT327 /PM8002, a bispecific antibody going after PD-L1/VEGF. The drug will enter registrational trials later this year. Additional studies next year will test it in combination with antibody-drug conjugates. By acquiring the six-year-old startup, BioNTech can speed up the development of multiple cancer drugs, have more control over the direction of the lead asset in the hot PD-L1/VEGF space, and gain access to a clinical team that can help the German drugmaker run more trials in China, Şahin said. BioNTech started in cancer, but vaulted into the global spotlight because of its Covid-19 vaccine. It’s invested heavily to make oncology its future , including several antibody-drug conjugates and an mRNA-based cancer vaccine to be used with checkpoint therapies. The PD-L1/VEGF space has become closely watched within cancer drug development thanks to Summit and Akeso’s claims in September that their drug, ivonescimab, beat Keytruda in a head-to-head study conducted in China. Former Seagen CEO David Epstein is also betting on the field with a preclinical PD-1/VEGF biotech known as Ottimo Pharma . Şahin has described BNT327 as being “ further enriched in the tumor microenvironment” than ivonescimab because of its PD-L1-directed approach, rather than honing in on PD-1. BioNTech will also go head-to-head with Keytruda, Şahin said in the interview. Merck’s medicine is the world’s top-selling treatment and has been approved across more than 15 different tumor types. “At the end of the day, there is no way around this,” Şahin said of the need to battle Keytruda head-on. But if it works out, the deal could be seen as a steal: Summit, for example, trades at a market value of around $15 billion, largely based around its success with its PD-1/VEGF drug. The deal comes 12 months after BioNTech said it could dish out more than $1 billion in biobucks to Biotheus to partner on the drug. The pair also had a pact for other antibodies . The deal will give BioNTech worldwide rights to the compound; Biotheus previously still owned the China rights. “From the financial standpoint, it is more or less paying the milestones earlier. From the value structure, it’s about getting better control of the assets, increasing the potential for additional clinical candidates,” Şahin said. Biotheus will also deliver to BioNTech a broad pipeline of clinical-stage antibodies, including work in TIGIT and Claudin18.2, and preclinical ADCs, which have become one of the buzziest drug approaches in oncology R&D. Biotheus has also said it’s conducting research in inflammatory and autoimmune diseases. It also gives BioNTech a foothold in China, where it has ADC deals with MediLink and Duality Biologics. “We are thrilled to deepen our bond with BioNTech,” Biotheus CEO Xiaolin Liu said in a statement. “We share the goal of advancing the development of BNT327/PM8002 for future combination therapies in the fight against cancer.” Biotheus last disclosed a $100 million Series D in March 2021, according to ChinaBio Today . General Atlantic, IDG Capital, Kunlun Capital and others have invested in the startup, according to Biotheus. Şahin told Endpoints he doesn’t know how much Biotheus has raised to date. The Biotheus acquisition is BioNTech’s biggest deal so far, Şahin said. It has made only a few acquisitions in its history, including $440 million for AI partner InstaDeep. Flush with cash from its Pfizer-partnered Covid vaccine, BioNTech has a hefty balance sheet and ended last quarter with €17.8 billion (about $18.8 billion) in cash, equivalents and security investments. After a “major pipeline reshaping” last year, the company wanted to focus on its existing drugs and partnerships, chief medical officer and co-founder Özlem Türeci told Endpoints News on the sidelines of this year’s American Society of Clinical Oncology meeting. “We are a very scientific company, which, however, does not have this ‘not invented here’ complex,” Türeci said in the June interview. “We are very curious about technological breakthroughs and bits and pieces, which can be implemented into a broader technology space.” The deal is expected to close in the first quarter of next year.