OncoC4 takes its Siglec-10 bet into the clinic

OncoC4, the private US biotech that made a splash last year by attracting BioNTech as a licensing partner for its anti-CTLA-4 antibody, is taking another pipeline project into the clinic: ONC-841, an anti-Siglec-10 MAb, will start phase 1 in June, updated listings on the clinicaltrials.gov registry reveal.

These also show first-in-human trial initiations for two cell therapies, two degraders, and an ADC against EGFR that had preclinical data at ESMO, among others. In the case of OncoC4, Siglec-10 is an extremely unusual industry target, but remarkably ONC-841 isn’t the company’s only shot at this goal: its pipeline reveals four other anti-Siglec-10 projects.

These include a Car-T approach (ONC-782), a bispecific antibody (ONC-783) and antobody-drug conjugate (ONC-784). But the naked MAb ONC-841 is its only clinical-stage oncology project targeting Siglec-10, and the only other notable industry asset with this mechanism, according to OncologyPipeline, is Allakos’s preclinical-stage AK007.

The theory is that Siglec-10, a checkpoint receptor expressed on tumour-associated macrophages, interacts with CD24, a “don’t eat me” signal like CD47 that allows tumours to evade the immune system. ONC-841’s phase 1 healthy volunteer trial is unusual in including a placebo cohort, though it will primarily test pharmacokinetics.

Last March OncoC4 got $200m from BioNTech for rights to the anti-CTLA-4 MAb gotistobart, which shortly afterwards entered phase 3. Gotistobart was originated by Oncoimmune, and after that company’s $425m sale to Merck & Co in 2020, a move driven by Covid assets, it was spun into OncoC4.

Unique

An even more unique target than Siglec-10 is DDX5, and its only exponent, the degrader project FL118, entered phase 1 this month. FL118 is apparently derived from the bark of a Chinese tree, and is owned by the US academic group Roswell Park.

Shenzhen TargetRx boasted early data at ASH with its BCR-ABL inhibitor TGRX-678, and now it’s taking TGRX-814, which inhibits BCL-2, into phase 1 in non-Hodgkin’s lymphoma. BCL-2 is a highly competitive space, however, featuring AbbVie/Roche’s marketed drug Venclexta and a host of pipeline assets that include BeiGene’s sonrotoclax.

Among first-in-human cell therapy trial initiations, Jiangsu Simcere is pursuing the CD19 antigen but with a Car-NK approach, coded F01, while a Canadian government effort, the British Columbia Cancer Agency, is going after CD22 with the Car-T project CLIC-2201.

At last year’s ESMO Shanghai Henlius presented preclinical data on HLX42, a topoisomerase-I inhibitor-containing, non-internalising ADC against EGFR, saying the compound showed tumour suppression in animal models resistant to current anti-EGFR therapy. A phase 1 trial is due to start in April.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 17 and 23 Jan 2024; the Haiyan Pharmaceutical study was listed in OncologyPipeline in October 2023.