Seres has commemorated the five-year anniversary of the mid-stage failure of its first microbiome project by doing the same thing all over again. This time it is SER-287 that has crashed, being beaten, numerically, by placebo in an ulcerative colitis study.
Though the group has canned the open-label and maintenance parts of the trial, it says it will continue developing ’287 in the hope of rescuing it – a trick it seemed to have pulled off with the earlier failure. But today’s misfire will cast a pall over the entire pipeline, and Seres’s share fell 56% this morning.
Today’s topline data come from the induction phase of the Eco-Reset study, assessing two doses of SER-287. Exactly what these doses were is unknown, but this is academic anyway since there was no significant difference between them – or between them and placebo – on the primary endpoint of remission.
|Topline data from Eco-Reset trial of SER-287|
|Dose||Full induction dose||Step-down induction dose||Placebo|
|Clinical remission rate (%)||10.3||10.6||11.6|
|Treatment-emergent adverse events (%)||67.6||46.2||50.7|
|Source: company release.|
The company hopes to do with ’287 what it did with SER-109. Following the latter’s phase 2 trial failure in Clostridium difficile infection in 2016, Seres undertook a post-mortem and, armed with the results, designed a different phase 3 study using a much higher dose of ’109.
To widespread astonishment this hit convincingly last year, and Seres hopes that ’109 will soon become the world’s first approved microbiome therapy.
The plan, therefore, is to resuscitate ’287 in a similar manner. On a conference call today analysts probed Seres management for possible explanations for the Eco-Reset failure. Any hope that the miss might be due to the Covid-19 pandemic disrupting the study was given short shrift, and the company denied that there were any major changes in manufacturing or patients’ baseline characteristics from the earlier, successful, phase 1b trial of ’287.
It seems that little in the way of explanatory factors – and therefore potentially fixable problems – will emerge before detailed microbiome and drug activity data from Eco-Reset are released in the coming months. This package will include information about engraftment of bacterial species, changes in microbe-associated metabolites and transcriptional data from intestinal biopsies to evaluate the up or downregulation of disease pathways.
After today’s washout, scepticism about microbiome-based projects will again be on the rise. Arguably Seres could be congratulated for monetising its pipeline where it could.
Under a 2016 agreement worth $120m up front, Nestlé Health Science has rights outside the US and Canada to SER-109 and SER-287, along with SER-301, another ulcerative colitis project currently in phase 1.
Just this month the Swiss group paid a further $175m to extend its rights to SER-109 worldwide.
But this is also problematic. After today expectations for ’287 will be minimal, so Seres’s valuation is now tied to its only other project for which the sellside is forecasting sales: SER-109, which is expected to bring in $326m in 2026, according to Evaluate Pharma.