Multi-specific antibodies and cell therapies enter phase 1

The private US biotech Affini-T Therapeutics, which recently moved to take its lead cell therapy into the clinic, will soon have two assets in human studies, newly published entries in the clinicaltrials.gov registry reveal.

First-in-human study initiations also include two Car-T therapies, and a BCL-6 degrader that Bristol Myers Squibb highlighted at last month’s R&D day. Meanwhile, Johnson & Johnson is putting into phase 1 a PSMA-targeting bispecific that will be of interest to those who had followed the recent ESMO conference.

The PSMAfore trial of Novartis’s anti-PSMA radiotherapy Pluvicto featured in an ESMO late-breaker that ultimately yielded a mixed dataset, while Ambrx presented early data on ARX517, an antibody-drug conjugate against PSMA, and saw its stock fall 40% since its ESMO abstract was revealed.

J&J’s JNJ-87189401 hits PSMA as well as the co-stimulatory molecule CD28, and will be combined with JNJ-78278343, an anti-KLK2 T-cell engager, in a phase 1 prostate cancer trial starting next month. Another anti-PSMA radioconjugate, Sinotau’s 177Lu-XT033, is due to enter its first human trial this month. 

Last month Bristol highlighted BMS-986458, a small molecule that degrades BCL6 and thus has potential in B-cell lymphomas driven by abnormalities in the BCL6 signalling pathway, and the asset is to enter phase 1 next month. It will join another Bristol degrader, BMS-986460, which has an undisclosed target and is in a first-in-human prostate cancer study.

Cell therapies

Affini-T’s AFNT-211 features among cell therapies entering first-in-human studies. It is an engineered T-cell receptor targeting KRAS G12V, a mechanism it shares with Affini-T’s other new phase 1 entrant, AFNT-111; however, while AFNT-111 uses a standard lentiviral approach, AFNT-211 is manufactured using a system called “Thrive”, and additionally employs a FAS-41BB switch receptor.

Also newly entering phase 1 is PersonGen’s UTAA09, a cell therapy against the well-known CD19 target, but which uses gamma-delta Car-T cells. This cell type is of interest because it can be given off the shelf, as an allogeneic therapy; at the forefront of gamma-delta Car-T cell therapy is Adicet's ADI-001, while another asset, Kiromic’s Deltacel (KB-GDT-01), is due to enter phase 1 in December.

An intriguing first-in-human entrant is a Bellicum-originated Car-T therapy against CSPG4 in head and neck cancer. CSPG4 (chondroitin sulfate proteoglycan 4) is said to play a role in the growth, survival and metastasis of tumour cells, and is overexpressed in several cancer types. OncologyPipeline reveals other work on CSPG4 to be preclinical, including two approaches from academia and an IgE antibody from Epsilogen. 

However, the Bellicum asset is also being led by academia, since Bellicum suffered a protracted share price collapse and discontinued all clinical trials in March, instead seeking “strategic alternatives”.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 17 and 27 Oct 2023; **investigator-initiated study, as Bellicum has discontinued clinical activities.