Crescent Biopharma has landed a Nasdaq listing in a reverse merger with GlycoMimetics and secured $200 million to support its pursuit of the white-hot PD-1xVEGF bispecific opportunity. GlycoMimetics took the deal, which gives its shareholders 3.1% of the combined company, after reporting a phase 2/3 failure.
Maryland-based GlycoMimetics began a strategic review in July after the FDA said bringing uproleselan to market in acute myeloid leukemia would require an additional clinical trial. The drug candidate, which is designed to disrupt E-selectin binding, suffered another setback Tuesday, when GlycoMimetics said it failed to improve event-free survival when added to chemotherapy in a phase 2/3 trial.
Thirty minutes after reporting the failure, GlycoMimetics shared details of the post-uproleselan future of its business. The biotech is merging with Crescent, a privately held startup that is part of the pack of drug developers targeting the PD-1xVEGF bispecific opportunity.
Interest in the mechanism went through the roof earlier this year when Akeso and Summit Therapeutics’ ivonescimab beat Merck & Co.’s blockbuster Keytruda in a phase 3 lung cancer trial in China. Crescent is transparent about the inspirations for its rival bispecific CR-001.
On a conference call to discuss the merger, CEO Jonathan Violin said Crescent “intentionally designed our molecule to replicate the pharmacology and pharmacokinetics of ivonescimab.” The biotech’s goal was to “avoid disrupting the balance of activities that have shown such striking promise in clinical trials,” the CEO said.
“We considered many other changes to this structure as we were designing CR-001, even small ones that could lead to some potential improvement,” Violin said. “But each time our team concluded the new design may actually increase the risks to efficacy, safety or both, and, no matter what, it would make it hard for us—and our investors—to assign a similarly compelling probability of success to CR-001.”
While biotechs typically talk up what makes their molecules different, Violin listed the ways in which his candidate is the same as the front-runner in the PD-1xVEGF space. Crescent’s CEO noted work to enhance CR-001’s stability and manufacturability but said the candidate “is a purpose-built molecule, designed to recapitulate precisely the pharmacology of ivonescimab.”
The nature of the PD-1xVEGF opportunity means being as good as other molecules may be good enough. Keytruda comprehensively won the fight for PD-1 market share, but Bristol Myers Squibb’s Opdivo and Roche’s Tecentriq still pulled in around $9 billion and $4 billion, respectively, last year. If PD-1xVEGF drugs supplant current checkpoint inhibitors, ivonescimab is unlikely to be the only blockbuster product.
Such thinking has triggered a tidal wave of activity. Crescent is taking a two-strand approach to carving out a piece of what is shaping up to be a highly competitive market. First, the biotech is looking at where VEGF and PD-1/L1 drugs have worked to find indications where it has a shot at being the first company to win approval for a bispecific that hits both targets.
Second, Crescent is keeping tabs on phase 3 programs that are getting started at Summit and BioNTech, another PD-1xVEGF front-runner. Violin said his team plans “to be fully enabled with the appropriate drug combinations to leverage data produced by those trials to support our clinical development strategy.”
Crescent is well behind Summit and BioNTech, but Violin believes the similarity of CR-001 to ivonescimab will enable fast progress. The biotech plans to file an IND around the end of 2025 and start reporting clinical data in the first half of 2026. Crescent wants to “gain confidence that data from just a few dozen patients can connect the dots back to the data produced” on ivonescimab, the CEO said.
A syndicate of investors led by Fairmount, Venrock Healthcare Capital Partners, BVF Partners and a large investment management firm has backed Crescent’s vision, coming together for a $200 million financing round that will keep the biotech going through 2027. By the time cash starts running low, updates on CR-001 and other PD-1xVEGF bispecifics should have started to reveal more about Crescent’s prospects.