Sutro calls time on folate

In some ways it's surprising that it took so long for Sutro's luveltamab tazevibulin to be canned. The writing had been on the wall for this project as soon as Genmab opted not to buy Sutro but instead to spend five times more on ProfoundBio a year ago.

Thursday's effective discontinuation of luvelta-T has come alongside the defenestration of Sutro's chief executive, Bill Newell, and the axing of nearly half its workforce to allow cash to stretch into late 2026. It brings to a close a troubled period for luvelta-T, during which competing folate receptor alpha-targeting ADCs were acquired while Sutro was left standing alone.

Sutro now plans to go back to the drawing board, switching attention to next-generation ADC projects, the first of which is STRO-004, targets tissue factor, and might enter the clinic this year. Notably, STRO-004 employs a topoisomerase 1 inhibitor payload; the fact luvelta-T used a different payload might have explained acquirers' lack of interest in it.

Strictly speaking luvelta-T is being "deprioritised" rather than being discontinued, and Sutro says it will redouble efforts to find a licensing partner for it. If it does pull off a deal that would extend its cash runway, though the key message is that its own investment in all luvelta-T indications is being wound down.

Hot target, wrong ADC

A partner might be attracted by luvelta-T's target – it was clear that FRα was highly interesting when AbbVie spent $10.1bn to acquire ImmunoGen in November 2023 – but questions remain about the molecule's design, which might be responsible for its underwhelming efficacy.

ImmunoGen's Elahere became the first anti-FRα ADC to secure approval, for second-line or later FRα-positive ovarian cancer. But Sutro insisted that luvelta-T could treat patients with lower levels of FRα expression, and doubled down on its Refrαme-01 study.

However, such claims were dealt a blow not only by unconvincing data, but also by Genmab pulling the acquisition trigger on a competitor, ProfoundBio. That private biotech was developing another anti-FRα ADC, rinatabart sesutecan, and even though this was earlier in development ProfoundBio attracted an acquisition price of $1.8bn – five times higher than Sutro's market cap at the time.

More doubts came last year when Bristol Myers Squibb discontinued an anti-FRα ADC with structural similarity to luvelta-T, and the final death knell came when a disappointing update to Refrαme-01 data at ESMO suggested waning efficacy, while rinata-S showed more impressive results, regardless of FRα expression.

What next?

Among the ADCs on which Sutro will now focus is a newly disclosed asset, STRO-006, which targets integrin αvβ6.

There is virtually no industry competition in αvβ6, and Sutro claims to have identified a "specific and selective" antibody where others have struggled. However, a IND filing isn't expected until mid-2026, at a time when the TF-targeting STRO-004 will deliver its first dose-escalation data. For STRO-004 there is also limited competition, though Pfizer's Seagen-derived Tivdak is no longer the only game in town.

Sutro has done the right thing to draw a line under luvelta-T, but it will need to raise more cash soon. This will remain a long shot until its new pipeline assets generate some promising data.

Sutro's new pipeline focus

Source: OncologyPipeline.