Eyeing clinical proof-of-concept for HER3 drug, Amgen-partnered biotech scores $125M for precision antibodies

Eyeing clinical proof-of-concept for HER3 drug, Amgen-partnered biotech scores $125M for precision antibodies

When it comes to redrawing the boundaries of what proteins are druggable, small molecules have soaked up the spotlight. Hordes of new entrants — inhibitors, allosteric modulators, degraders — promise to make a big difference by hitting disease-causing proteins at the right spot.

Over the last five years a biotech out of Singapore has been trying to show that the same approach can be applied to antibodies. Now Novo Holdings is leading a $125 million Series C designed to push them toward clinical proof-of-concept.

It all started, Hummingbird CEO Piers Ingram said, with a target that’s puzzled him since his PhD years: HER3.

Despite ample evidence that it should be a great drug target, none of the antibodies previous researchers have generated had the expected biological activity. When he and co-founder/CSO Jerome Boyd-Kirkup dug into it, they found that these HER3 inhibiting antibodies all shared very similar mechanisms of action. And it wasn’t optimal — they often always stopped one route of activation, leaving a “huge gaping hole” for the protein to be active.

Their hypothesis was simple: You probably need to shut down the whole thing. Executing it was the bigger challenge, as the B cells that see the antigen first usually are the ones that spawn the majority of antibodies, all targeting the identical, most immunogenic — a phenomenon known as immunodominance. Often, these epitopes are not the spots that are most functionally useful as a drug.

Rather than feeding antigens to B cells, Hummingbird takes a guided approach, first leveraging computational modeling to predict the regions of interest on the protein then engineering antibodies that are driven to bind to those specific epitopes.

Hummingbird has generated four in-house antibodies on this platform, with a lead candidate targeting HER3 and others hitting VISTA, BCMA-TACI and an undisclosed protein associated with lupus.

Amgen has also signed on for a discovery pact, reserving $100 million each for up to 12 projects.

“If you are lucky and nature gives you good antibodies the first time around, then you don’t have to worry about any of these cool technologies,” Ingram said. But if you’re not, “it’s really a huge opportunity to take advantage of all of the structural and functional insights that we have around protein targets these days and then use the power of antibodies on these as well as small molecules.”

The company now has 65 staffers, with the research team based in Singapore and a development group in the US.

The Series C comes two years after the last round, which Ingram said unlocked the team’s creative potential around the technology. In addition to Novo, the Series C syndicate features Frazier Healthcare Partners, Octagon Capital, EDBI, AMGEN Ventures, DROIA Ventures, Morningside Ventures, Pureos Bioventures, Polaris Partners, Affinity Asset Advisors, Ally Bridge Group and Altrium Capital Management. Existing investors including SK, Heritas Capital, and Mirae Asset Venture Capital also joined the round.

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