ProfoundBio takeout shines a light on Sutro

Given the frenzy of deals concerning antibody-drug conjugates it takes a lot to move the needle, and today’s $1.8bn takeover of ProfoundBio by Genmab is notable for a number of reasons. Perhaps most astonishing is the fact that the target is a private company seeded just three years ago, since when it had raised only $247m from venture financiers.

ProfoundBio’s focus on topoisomerase 1 inhibitor payloads, which have elicited significant deal interest, helps explain Genmab’s enthusiasm, and the takeover signals further rehabilitation of folate receptor alpha (FRα) as an oncology target. However, investors in Sutro will today be wondering why it was ProfoundBio and not their company that got acquired.

ProfoundBio’s small pipeline is headed by rinatabart sesutecan, an ADC against FRα that generated first-in-human data at last year’s SITC conference, showing a 38% ORR among 21 evaluable solid tumour patients, apparently across various levels of FRα expression and with no lung or eye toxicity.

Sutro’s lead asset is the FRα-targeting ADC luveltamab tazevibulin, which has been in the spotlight since AbbVie’s $10.1bn acquisition last November of ImmunoGen, maker of the industry’s most advanced FRα ADC, Elahere. With Sutro’s market cap now down to just over $300m it’s a relevant question why Genmab chose instead to acquire the much pricier ProfoundBio, at a huge premium.

ImmunoGen 2.0?

It’s likely that Genmab wanted to follow in AbbVie’s footsteps by getting its hands on an anti-FRα ADC, but was seeking one that uses a more in-vogue payload, namely a topoisomerase 1 inhibitor.

Rinata-S fits this bill, and luvelta-T doesn’t: the Sutro project, like Elahere itself, uses a tubulin inhibitor-based payload, while ProfoundBio’s comprises camptothecin. All three have cleavable linkers, but the drug-to-antibody ratio, another relevant factor in ADC design, seems to be much higher with rinata-S than the other two.

Sutro also faces a separate problem, having long touted the possibility of an accelerated approval for luvelta-T in ovarian cancer. The issue here is that as of 22 March Elahere carries full US approval in this setting, something that has likely closed off the accelerated pathway for similarly acting rivals.

Sutro argues that Elahere is available only for ovarian cancer with ≥75% FRα expression, while luvelta-T has shown remissions in a small number of patients with FRα expression down to 25%; at best this might imply that an accelerated pathway for luvelta-T exists only in 25-75% expressers.

And Sutro has had its share of setbacks, quietly shelving two pipeline projects, and seeing Bristol Myers Squibb walk away from another. Yesterday’s licensing deal with Ipsen brought some validation, but included what seemed to be a negligible up-front fee.

Pedigree

ProfoundBio might be a young, private biotech with little visibility, but it boasts a management team that used to work at Seagen, the ADC pioneer now owned by Pfizer.

Its pipeline also includes two other clinical-stage ADCs – PRO1160, which targets CD70, and PRO1107 (PTK7). Interestingly, only the former uses a topoisomerase inhibitor payload, the latter comprising monomethyl auristatin E with a next-generation linker.

On an investor call today Genmab highlighted the fact rinata-S in ovarian cancer could be marketed to the same gynaecologist oncologists who prescribe its Pfizer-partnered cervical cancer drug Tivdak.

That it chose an asset hitting FRα shows just how far this target has come in recent years, after falling virtually into obscurity after the collapse of Endocyte’s vintafolide. Recent deals, apart from ImmunoGen, include the extraordinary $650m up front that Bristol paid in 2021 for rights to Eisai’s farletuzumab ecteribulin, and Lilly’s takeover of Mablink for an undisclosed amount last year.

ProfoundBio’s takeout will keep further deal hopes alive.

ADCs targeting folate receptor alpha

Notes: ^drug-to-antibody ratio; ^^biparatopic; *Elucida calls this a “C’dot conjugate”; **uses a targeting ligand ~half the size of a MAb. Source: OncologyPipeline.