Sensei keeps its eye on VISTA

In the early days of the immuno-oncology revolution one view was that the successes of CTLA-4 and PD-(L)1 blockade would be followed by a multitude of new mechanisms that would transform the treatment of cancer.

It hasn’t quite panned out that way: only Lag3 has delivered a hit, and of the more prominent approaches only TIGIT and Tim-3 can arguably be said to remain in play. So spare a thought for tiny Sensei Biotherapeuetics, which focuses on VISTA, one of those formerly hotly touted immune regulatory checkpoints.

Sensei’s doubling down on VISTA – its current lead project is an anti-VISTA MAb, SNS-101 – is notable given the lack of anything substantial to shout about for this mechanism. Only today another micro cap biotech, Kineta, moved to restructure, cut 64% of its workforce including the chief executive, and wind down a phase 1 trial of its own anti-VISTA MAb, KVA12123.

Kineta gained a public listing by reversing into the shell of Yumanity Therapeutics, and as recently as last week boasted of presenting preclinical data featuring KVA12123 at next month’s AACR Blood Cancer Discovery symposium. Today the group said enrolment of new patients into KVA12123’s solid tumour clinical trial was being stopped.

Sensei’s chances

Meanwhile, Sensei went public in a 2021 Nasdaq float that raised $133m on the promise of a bacteriophage-based immunotherapy called SNS-301, but that soon failed in head and neck cancer. The SNS-301 setback prompted Sensei to turn to the anti-VISTA MAb SNS-101. 

What are SNS-101's chances of success? The first anti-VISTA MAb to go into the clinic, Johnson & Johnson’s onvatilimab, was sunk by cytokine release-related encephalopathy. Curis gained rights to it, but despite proposing a plan to mitigate cytokine release, which it said was a likely on-target effect, it quietly dropped onvatilimab a couple of years ago.

Curis’s small-molecule attempt at targeting VISTA, CA-170, still appears in its pipeline even though no new clinical trials have been initiated since the last ended four years ago, and a separate radioligand based on onvatilimab has also been canned.

Counting Kineta’s KVA12123 SNS-101 remains one of just four active clinical assets, according to OncologyPipeline, the other two belonging to South Korea’s PharmAbcine and Hummingbird Bioscience, a Singapore-based company. Sensei yesterday said phase 1 Libtayo combo results would come together with SNS-101 monotherapy data in the second quarter, three months before earlier guidance. 

At least the reason behind Kineta’s setback doesn’t immediately seem to be VISTA related. The company said its move to “explore strategic alternatives” came about because some investors who had agreed to put up private money were now withdrawing their support.

Projects targeting VISTA (V-domain immunoglobulin suppressor of T cell activation)

Source: OncologyPipeline.