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Swiss antibody player Numab saw its last raise come in at just under $24 million, a Series B that closed in March 2020. But Thursday, the biotech brought in a whole new heaping of cash. Numab secured a Series C of 100 million CHF, or roughly $110.6 million, to continue advancing its slate of multispecific offerings through preclinical and clinical studies. Its lead candidate, a trispecific that hits 4-1BB, PD-L1 and HSA, has entered its Phase I safety studies and Numab hopes to use Thursday’s funds to prep three Phase II cohorts for a proof-of-concept study sometime around the end of this year. Novo Ventures and HBM Partners co-led the round, joining Numab’s investor syndicate for the first time. The company’s founding research comes from a team that worked together at another Swiss outfit called ESBATech, CEO David Urech told Endpoints News, where they developed an antibody fragment platform. Numab aims to take that a step further, using such fragments as building blocks for their multispecific candidates. Numab’s platform itself, Urech says, comprises three aspects in order to “maximize success and repeatability.” The first utilizes a rabbit model to create monoclonal antibodies, the second humanizes the antibodies and splits them into the fragments and the third matches them to the multispecific format, allowing Numab to target up to six different antigens in one molecule. That lead candidate, known as NM21-1480, is designed to hit its three targets in a way that Urech says helps T cells overcome an “exhaustion” of sorts. In many cases, he says, the “brake” released by targeting the traditional PD-1 checkpoint is not enough to fully restart the body’s immune system near the tumor. But by also acting as a 4-1BB agonist, Numab aims to modulate both pathways while preventing the systemic toxicity associated with the activation signals. The challenge is picking the right dose and concentration, Urech says. “That’s really an artwork. Otherwise you end up with a molecule that at a certain dose either only blocks PD-L1 or agonizes 4-1BB,” he told Endpoints. “Our molecule is designed to do both at the same time and this profile, this characteristic, is the key differentiator that was convincing to our investors.” NM21-1480 is developed together with CStone Pharmaceuticals, who has the rights to commercialize the program in China, Macau, Hong Kong, Taiwan, South Korea and Singapore. They’re shooting for a monotherapy treatment once the candidate moves into its next stage of development. Numab is applying the same multispecific principles to its other programs as well, including another trispecific for atopic dermatitis. With this program, for which Urech declined to disclose the antigen targets, the biotech is seeking to reduce both the inflammation and pruritus associated with the condition. The biotech hopes to push the AD program into the clinic with Thursday’s raise and file an IND early next year. There’s also a slate of preclinical T cell engagers that Urech says are tetra-specific, and eventually the platform could develop antibodies that hit as many as six targets at once. In addition to Novo Ventures and HBM, other new investors included Forbion, Cormorant Asset Management, BVF Partners, RTW Investments, BlackRock and Octagon Capital Advisors. Other existing investors also participated.