MediLink beats Sotio to the punch

The latest industry projects to enter human studies include a new player to the anti-CDH17 ADC field, MediLink's YL217. CDH17 features just two other clinical-stage players, but was put in the spotlight this month when Sotio revealed it to be the target of SOT109, an ADC derived from an antibody originated by MediLink's Chinese competitor Biocytogen.

Another player with a preclinical CDH17-targeting ADC, LaNova, is also going into the clinic with a separate project, LM-168, the latest listings on clinicaltrials.gov reveal. LM-168 is one of four industry projects newly into phase 1 whose targets haven't been revealed, though an educated guess can be made about at least two of these.

Sotio aims to file an IND for SOT109 in the second half of this year, but it will be beaten by MediLink, which announced the clearance of a US IND for YL217 just last month, and aims to start phase 1 in May. CDH17 is said to be overexpressed in gastric, pancreatic and colorectal cancers.

Undisclosed

As for the clinical entrants with undisclosed targets, these include Incyte's INCB177054, AbbVie's ABBV-324 and Qilu's QLS1209, all of which are to begin human studies next month. Curiously, LM-168 doesn't appear in LaNova's pipeline, and the clinicaltrials.gov listings for it and for ABBV-324 give no clues as to the projects' respective molecular targets.

However, the entry for INCB177054 lists prior treatment with a DGK inhibitor as an exclusion criterion, so it's likely that this is the mechanism of action of this new Incyte molecule. What's more, Incyte is known to have filed a patent on compounds that inhibit DGK.

Clinical-stage projects acting on DGK (diacylglycerol kinase) include Bristol Myers Squibb's BMS-502, which hits DGKα/ζ, Bayer's BAY 2862789 and Gilead's GS-9911. The latter two are said to inhibit DGK's α isoform.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 5 and 13 Mar 2025.

It's a similar case for Qilu's QLS1209, whose clinicaltrials.gov entry cites among its exclusion criteria prior treatment with a PKMYT1 inhibitor.

PKMYT1 inhibition is a synthetic lethality approach where several companies are still active, despite Repare’s lunresertib having disappointed – at least when given as monotherapy. Further evidence for QLS1209 being a PKMYT1 inhibitor is that both Qilu's study, and several trials of lunresertib, list CCNE1 amplification/FBXW7 mutation and PPP2R1A mutation as inclusion criteria.

Meanwhile, Biohaven recently signalled its intent not only to gain a bigger presence in oncology but also to become a notable ADC player, building on the 2021 acquisition of Kleo Biosciences, and last year's takeover of Pyramid Biosciences, which brought with it the TROP2-targeting asset BHV-1510.

BHV-1510 is based on a topoisomerase 1 inhibitor payload licensed from GeneQuantum, and in January 2025 Biohaven licensed exclusivity to use this for up to 18 more ADC targets. The next one of these is FGFR3, targeted by BHV-1530, whose first-in-human study begins this month.