Another in vivo Car speeds into the clinic

Two areas that continue to attract significant amounts of development dollars are in vivo Car-T therapy and PRMT5 inhibition. Recent weeks have seen disclosure that biotech projects featuring each approach – PersonGen’s LV009 and Abbisko’s ABSK131 respectively – have entered first-in-human trials.

LV009, an anti-CD19 lentivirus-based in vivo Car-T, is especially interesting, as its entry into human studies makes it the 14th such asset in industry-sponsored clinical development for cancer, according to OncologyPipeline. That’s an impressive achievement for a field whose first clinical entrant, Interius’s INT2104, was cleared for human study just 18 months ago.

In the meantime, in vivo Car-T has attracted significant buy-in from big pharma, with deals seeing Bristol Myers Squibb buy Orbital Therapeutics, Gilead's takeover of Interius, AbbVie's Capstan takeout and AstraZeneca's move on EsoBiotec.

At the same time the only human data so far amount to case reports in four patients receiving Kelonia’s KLN-1010, and in four patients given EsoBiotec’s ESO-T01; both are BCMA-targeting in vivo Car-Ts. PersonGen, a Chinese cell therapy company, has worked extensively on ex vivo anti-CD19 projects, but LV009 appears to be the company’s first foray into in vivo Car-T.

PRMT5

Meanwhile, in small-molecule approaches PRMT5 inhibition has a patchy track record, with Tango discontinuing a brain-penetrant molecule, TNG908, and Amgen tinkering with the dosing of its contender AMG 193.

But interest continues nevertheless, with two assets that will shortly be in pivotal development, Bristol Myers Squibb’s Mirati-originated BMS-986504, and Tango’s take two, vopimetostat; Ideaya, having lost GSK for a pair of other projects, has pinned its hopes on the PRMT5 inhibitor IDE892, which entered human studies last month.

Now comes the disclosure that China’s Abbisko has taken its own PRMT5 inhibitor, ABSK131, into a phase 1 solid tumour study; this apparently began last July, but its listing has only just appeared on the clinicaltrials.gov registry, and Abbisko still lists ABSK131 as being in “IND enabling” trials. The company’s pipeline also shows a separate PRMT5 inhibitor, ABSK132.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 12 and 18 Dec 2025.

Other recent human trial entrants worthy of note include Haisco’s BCL6 degrader HSK47977. This is only the third BCL6 degrader into the clinic, according to OncologyPipeline, after Bristol Myers Squibb’s BMS-986458 (81% ORR among 17 relapsed lymphoma patients) and Arvinas’s ARV-393.

Like ARV-393, HSK47977 is claimed to be a “protac” degrader, and Haisco has worked preclinically on a separate BCL6 degrader, HSK43608, which appears to have been shelved after being presented in a 2024 AACR poster. And Haisco also has a PRMT5 inhibitor, HSK41959, in phase 1.

Radiopharmaceuticals continue to be a popular approach, and the latest into the clinic is Molecular Partners with MP0712, an anti-DLL3 molecule based on a January 2024 deal with OranoMed. That tie-up focused on the development of “darpin” therapeutics using Orano’s lead-212 radioisotope, and MP0712 looks like the first resulting asset to start human testing.

Perhaps a less promising approach is SMARCA2 degradation, where Prelude discontinued PRT3789 and PRT7732. Nevertheless, Lilly has bought into Foghorn’s SMARCA2 inhibitor (LY4050784/FHD-909) and degrader approaches, and the next asset to watch is Plexium’s PLX-61639, which went into phase 1 last month.