A mystery Moderna asset hits the clinic

Moderna has recently made a renewed push into oncology, and the company is showing its intent by moving a mystery T-cell engager, mRNA-2808, into the clinic, according to recent listings on clinicaltrials.com.

Meanwhile, Beijing Konruns Pharmaceutical is joining the likes of Pfizer, Menarini and Olema in KAT6 inhibition, and Lilly could challenge Novartis with a radioconjugate targeting GRPR. Conversely, K36 Therapeutics is the only group pursuing NSD2 inhibition, according to OncologyPipeline.

Moderna multispecific?

All Moderna is saying about mRNA-2808, which is set to hit the clinic in October, is that it’s a T-cell engager. When asked by ApexOnco, a company spokesperson declined to disclose the project’s target.

However, given that the newly listed trial is in multiple myeloma, it’s possible that mRNA-2808 is the same project that featured in a preclinical presentation at last year’s ASH meeting. That asset comprises mRNA that encodes three T-cell engagers, targeting BCMA, FcRH5, and GPRC5D, in a single product.

Moderna’s mRNA rival BioNTech has already reported early data with an mRNA-encoded T-cell engager, BNT142 – but that only hits one target, Claudin6. Results, presented at ASCO, were lacklustre, but the group believes that it has at least shown proof of concept.

Meanwhile, others are taking a more typical trispecific approach in multiple myeloma, such as Johnson & Johnson with its BCMA x GPRC5D T-cell engager JNJ-79635322, and Ichnos Glenmark, whose BCMA x CD38 project ISB 2001 recently tempted AbbVie.

Novel mechanisms 

Legend Biotech’s newly clinical Car-T, LCAR-F33S, is also thought to hit FcRH5 – one of the possible targets of mRNA-2808. There is little other industry activity here, with the only other clinical-stage project being Roche’s T-cell engager cevostamab, according to OncologyPipeline.

Meanwhile, K36 appears to be the only biopharma company taking aim at NSD2, although a preclinical degrader from the University of Alabama at Birmingham featured at AACR in 2024. NSD2, also known as MMSET, is said to be overexpressed in various cancers including breast, renal and prostate; the last is where K36 is testing KTX-2001. The group also has another similarly acting project, KTX-1001, in phase 1 in multiple myeloma. 

KAT6 & GRPR competition

Other targets represented in this analysis are more popular. KAT6 inhibition has become increasingly important for Pfizer’s breast cancer pipeline since recent disappointments with its Arvinas-partnered estrogen receptor degrader vepdegestrant, but the big pharma is facing growing competition in a field it once had to itself.

Menarini and Olema have now gone into the clinic, and Konruns should do soon; however, a phase 1 trial of the last group’s hopeful, KC1086, will take place only in China. Other KAT6 inhibitors could also soon enter human trials, including BeOne’s BG-75202 and Ideaya’s IDE251.

Gastrin-releasing peptide receptor (GRPR) is said to be overexpressed in various tumours, and Lilly will test its candidate, LY4257496, in breast, colorectal, prostate, and endometrial cancers in its phase 1 trial.

Novartis already has a phase 1/2 breast cancer study under way with its GRPR-targeting radioconjugate, 177Lu-NeoB or AAA603, which came via its 2018 purchase of Advanced Accelerator Applications. Another player here is Lantheus, which gained a diagnostic-theranostic GRPR pairing through a deal last year with Life Molecular Imaging.

Lantheus's LNTH-2402 could go into the clinic soon. Both 177Lu-NeoB and LNTH-2402 use lutetium, but the radioisotope employed in Lilly's LY4257496 is undisclosed.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 3 and 12 August 2025.