Dispatch Bio, which came out of stealth mode last year with much fanfare and $216m of venture financing to its name, just became a clinical-stage biotech. That’s courtesy of DV-10, an oncolytic virus that delivers the BCMA antigen, just revealed on clinicaltrials.gov to have started its first-in-human trial.
New listings also reveal the entries into phase 1 of Ideaya’s KAT6/7 inhibitor, one of several molecules that company has recently advanced into clinical development, and of a molecule that shares its mechanism with the high-profile bispecific ADC izalontamab brengitecan. One reason for the interest in Dispatch is that this company counts Dr Carl June among its co-founders.
It’s likely thanks to this endorsement that Dispatch has been able to raise as much as it has in private money. June is notable for being among the scientific team that originated Novartis’s Kymriah, and more recently for co-founding the in vivo Car-T company Capstan, sold to AbbVie for $2bn; his Tmunity venture ended in failure, however.
BCMA delivery
The little disclosed so far about Dispatch suggests that this company is exploring an unusual idea. A poster at last year’s SITC meeting presented DV-10 as a tumour-specific adenovirus engineered to deliver a form of BCMA modified to eliminate its signalling domain; DV-10 also expresses IL-18 and CXCL9 to enhance immune activation and tumour microenvironment infiltration.
Once DV-10 infects tumour cells these then express BCMA. Because concurrently with DV-10 an anti-BCMA Car-T therapy is also administered – in the case of the first-in-human study this is Bristol Myers Squibb’s Abecma – the killing of the cells that express BCMA ensues.
The need to combine DV-10 with Car-T necessitates standard lymphodepletion, at least in the first-in-human trial. Perhaps the most curious aspect of this study is that it concerns not multiple myeloma (the natural target of an anti-BCMA therapy) but gastrointestinal cancers.
Recently disclosed first-in-human studies*
Recent first-in-human trial initiations are also notable for including the KAT6/7 inhibitor IDE574, which features among a PRMT5 inhibitor, anti-DLL3 ADC and anti-B7-H3 x PTK7 ADC as assets Ideaya has recently taken into the clinic.
The iza-bren me-too is Huadong Medicine’s HDM2024, and like the Bristol/SyntImmune ADC this is known to employ a topoisomerase 1 inhibitor payload, though beyond this any differences and similarities are unclear. And yet another in vivo Car-T project has entered human testing, Byterna Therapeutics’ BR101 – a prominent move given Lilly’s $3.25bn acquisition of Kelonia last week.
Shanghai Henlius is advancing HLX3902, a CD28-co-stimulated T-cell engager against Steap1, adding to more prominent molecules with this target including Amgen’s non-co-stimulated T-cell engager xaluritamig and AbbVie’s anti-PSMA x Steap1 ADC ABBV-969. The most obvious setting for Steap1 blockade is prostate cancer, as is the case for another novel target, ACP3.
Coincidentally, a new anti-ACP3 radioconjugate from FindCure Biosciences, FC516, is also entering clinical trials. Bristol last year gave ACP3 its biggest endorsement to date when it paid $350m up front to gain worldwide rights to Philogen’s diagnostics and therapeutics against this target.
