Merck joins Alpine's CD28 efforts, but Regeneron leads

Snippets

A new clinical collaboration between Alpine and Merck & Co could well represent little beyond a supply deal. But the news shines a light on an immuno-oncology target that few are vested in, besides what looks like an outsized interest from Regeneron. The target is CD28 – infamously pursued by Tegenero with disastrous consequences 15 years ago – which is involved in T cell activation; at Asco this year Alpine appeared to show this could be hit safely. A phase 1 basket trial called Neon-2 has begun testing Alpine’s ALPN-202, which the company describes as a CD28 co-stimulator and dual checkpoint inhibitor, in combination with Keytruda, it was announced yesterday. The collaboration presumably involves no formal deal terms as none were detailed, and an email to Alpine seeking further information was not answered. Regeneron, meanwhile, has three CD28-targeted projects in the clinic, in an effort that Bernstein analysts recently described as potentially the US biotech’s third franchise. Keenly awaited data are unlikely to emerge until next year. But with Merck seeming to tip its hat at the mechanism, and existing interest from Sanofi and Johnson & Johnson, Alpine stands out starkly as a rare unencumbered party.

Targeting CD28 - a thin pipeline 
Project Target Company  Note 
REGN5678 PSMAxCD28 MAb Regeneron In Ph1/2 prostate cancer trial.
REGN5668 MUC16xCD28 MAb Regeneron In Ph1/2 ovarian cancer trial.
REGN7075 EGFRxCD28 MAb Regeneron In Ph1/2 solid tumour basket trial
SAR442257 CD38 MAb Sanofi In ph1 blood cancer trial.
ALPN-202 CD28xPD1xCTLA4 Alpine  Neon-2 trial underway 
Prostate cancer project CD28xPSMA (?) Bispecific  Xencor/J&J  Prostate tumour target undisclosed; in preclinical development. (2020 deal).
Other research projects CD28xB7H3 bispecific  Xencor (wholly owned)  Preclinical.
Source: Bernstein research, company statements. 

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