Chemomab Therapeutics has shared phase 2 results it claims show CM-101 is a triple threat in primary sclerosing cholangitis (PSC), simultaneously tackling fibrosis, inflammation and cholestasis. But the pitch fell flat with investors, who sent the biotech’s stock down around 18% when the market opened.
Investigators randomized 76 participants to receive placebo or one of two doses of CM-101, a CCL24 neutralizing antibody that Chemomab is pitching as the only PSC candidate targeting inflammation and fibrosis. The primary endpoint covered safety and tolerability. Adverse events, mainly fatigue, headache and itching, were generally mild to moderate and evenly split between the placebo and CM-101 arms.
That was enough for the study to hit its primary endpoint. But the meat of Chemomab’s update lies in the secondary endpoints, where the biotech has begun to show whether CM-101 can live up to its billing as a disease-modifying therapy that is differentiated from the competition.
Chemomab talked up the results, hailing CM-101 as the first candidate to show clinically relevant effects on all three components of PSC and the first linked to a statistically significant reduction in liver stiffness after 15 weeks. However, scratching the surface of the data provides scope for a more skeptical reading of the results.
The biotech includes 60 subjects in its analysis of liver stiffness, a noninvasive measure of liver disease. Liver stiffness declined in the CM-101 arms while rising in the placebo group, but neither dose achieved statistical significance. Chemomab’s claim of statistical significance is based on a subgroup of 33 patients that it classed as having moderate or advanced disease. The subgroup p-values were both 0.01.
Liver stiffness was numerically higher in the CM-101 than in the placebo cohorts at baseline. The figures for the two treatment arms were 12.5 and 11.7 compared to 9.3 for the control group. The biotech said the cohorts had similar baseline values “in general.”
Chemomab also shared data on itching, claiming patients on CM-101 had reduced pruritus scores compared to placebo starting as soon as six weeks after their first dose. But, while some separation was seen after six weeks, the high dose was statistically no better than placebo at the end of the trial. The low dose squeezed below the bar for statistical significance with a p-value of 0.047.
The itch analysis included 63 patients. Chemomab classified 66 of the 76 enrolled participants as “double blind completers.” The other 10 patients were only included in the safety population for reasons such as “adverse event” and “inadequate baseline labs.”
For the enhanced liver fibrosis score analysis, Chemomab included 35 patients. The biotech said people on the high dose stayed consistently below a recognized threshold for predicting clinical events. However, the low dose crossed the threshold and performed numerically worse than placebo after 15 weeks. The p-value for the high dose versus placebo was 0.09.
The biotech is aiming to meet the FDA to discuss a potential registrational trial in the fourth quarter and receive written feedback in the first quarter of 2025. Chemomab, which was set to run out of money in the first quarter of 2025, disclosed a $10 million private placement alongside the data. The investment will extend the biotech’s cash runway through the beginning of 2026.