Sutro goes back to work

After implementing two rounds of workforce reduction and cost-cutting this year, the troubled antibody-drug conjugate player Sutro has gone back to the business of drug development. An R&D day on Wednesday highlighted the company’s new pipeline lead, the anti-tissue factor (TF) ADC STRO-004, and on the same day this project’s first-in-human study appeared on clinicaltrials.gov.

This features among several new entries on the registry, which also include a trio of undisclosed assets from Daiichi, Bristol and Boehringer. For investors in Sutro, whose shares closed up 15% on Thursday, STRO-004 is one of a number of assets to focus on after the shelving in March of the anti-folate receptor alpha ADC luveltamab tazevibulin.

It was then that the group switched to TF and STRO-004 as its new lead, alongside the integrin αvβ6-targeting conjugate STRO-006 plus several early-stage undisclosed dual-payload ADCs. Among the disclosures at Sutro’s R&D day was that the company’s first dual-payload ADC would be STRO-227, which targets PTK7.

STRO-227 apparently lies outside Sutro’s dual-payload ADC discovery collaboration with Astellas, whose first (still undisclosed) project is due to start clinical testing early next year. Meanwhile, STRO-227 is somewhat further behind, with an IND submission not expected until 2026/27.

However, the fact Sutro has selected PTK7 as its target will raise eyebrows, since this has seen notable discontinuations of ADCs from Genmab (GEN1107) and AbbVie/Pfizer (cofetuzumab pelidotin). Nevertheless, Sutro says cofetu-P “validated” PTK7 clinically, and now discloses that STRO-227 uses exatecan and MMAE payloads at drug-to-antibody ratios of 8 and 2 respectively.

STRO-004

As for Sutro’s new lead, STRO-004 has been taken into phase 1 in cancers known to express TF, but apparently not preselected for high expression levels of this antigen.

Pfizer/Astellas’s Tivdak is the only approved anti-TF ADC, and beyond this STRO-004 is among just six others in clinical development, including Evopoint’s XNW28012 and Exelixis’s XB371, according to OncologyPipeline. And regarding the anti-αvβ6-targeting ADC STRO-006, Sutro says it will submit an IND for it next year.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 9 Oct and 12 Nov 2025.

Beyond Sutro, clinicaltrials.gov reveals the recent entry into phase 1 of several other projects, of which perhaps the most intriguing is the private biotech EvolveImmune’s EVOLVE-104, a T-cell engager targeting ULBP2.

This is no ordinary T-cell engager, however, employing what EvolveImmune calls "integrated co-stimulation" via the additional engagement of CD2 to amplify tumour killing, in addition to CD3-based engagement of T cells. A year ago AbbVie bought into this approach, giving EvolveImmune $65m up front in a discovery collaboration.

Meanwhile, DS-3790a is the latest Daiichi project to enter the clinic without having its target disclosed. Similar secrecy surrounds Boehringer Ingelheim’s BI 3810944 and Bristol Myers Squibb’s BMS-986523, though the new clinicaltrials.gov entries give a good indication of those last two molecules’ mechanisms of action.

One part of BI 3810944’s study says patients’ BRAF expression levels must be known before enrolment, while that of BMS-986523 mandates KRAS mutation or amplification. It’s possible that the two projects act on those respective proteins.