Numab Therapeutics has raised CHF 100 million ($111 million) to expand clinical development of its lead PD-L1x4-1BB drug candidate into multiple cancer indications. Novo Ventures and HBM Partners co-lead the series C round with assists from investors on both sides of the Atlantic.
The therapeutic potential of pairing PD-L1 blockade with 4-1BB co-stimulation in a single molecule has attracted multiple drug developers. Genmab is working on a candidate with BioNTech; Servier is collaborating with Pieris Pharmaceuticals; and F-star Therapeutics and Merus are separately pursuing the opportunity.
Switzerland-based Numab entered the clinic more than a year after Genmab and BioNTech, bigger companies that have previously delivered successful products. Yet, Numab is confident it can stand out from the crowd.
“Our lead compound NM21-1480 is fundamentally differently designed than competitive programs. It's not based on an IgG scaffold, but it's a fragment-based multispecific. So, that means it has no Fc portion. There is much reduced risk for off-target or off-tumor interactions. That's one angle. And the other very important differentiator is the asymmetry in binding strength to the two targets,” Numab CEO David Urech, Ph.D., said.
NM21-1480 is designed to have a very high affinity for PD-L1 but a dialled down affinity for 4-1BB. Numab decided on that asymmetry in binding strength after its studies suggested issues arise when the affinities are too close.
“The activity on the 4-1BB part declines when you reach a concentration that saturates PD-L1. So, that means a molecule with identical affinity to both targets ... will either completely block PD-L1 or agonize 4-1BB, but it cannot do both at maximal capacity,” Urech said.
Numab has persuaded investors of the merits of its approach. Having received money from backers including 3SBio-subsidiary Sunshine Guojian, Eisai and former Novartis CEO Daniel Vasella in its 2020 series B round, Numab expanded its syndicate to reel in a far bigger sum to support its expanding ambitions. Forbion, Cormorant Asset Management, BVF Partners, RTW Investments, Octagon Capital Advisors and funds and accounts managed by BlackRock joined the co-leads in the series C round.
“We initiated our fundraising process in the U.S. and actually readily got traction there. Interest in the investor community, but also amongst analysts, was immediately there. Our strategy was to bring in reputed life science investors. We wanted to have European as well as U.S. investors,” Urech said.
The money will enable Numab to expand development of NM21-1480. Numab began testing its lead candidate, which has a HSA-binding motif to extend its half-life, in humans last year. Once Numab has determined the maximum tolerated dose, it plans to run multiple clinical proof-of-concept trials in different indications in parallel, enabling it to advance quickly in a competitive space.
Numab will also use the money to support development of an earlier-stage treatment for atopic dermatitis. The multispecific candidate is designed to tackle the inflammation and itching associated with the disease. Numab expects to advance the program to an IND next year.