Chasing Bristol Myers and Pfizer, Connect fails phase 2 ulcerative colitis trial but spies path forward

Connect Biopharma’s pursuit of Bristol Myers Squibb and Pfizer has hit trouble, with a midphase failure in ulcerative colitis sending the biotech’s stock down over 30% to $1.30 apiece in premarket trading despite its positive spin on the results.

BMS’ Zeposia and Pfizer’s etrasimod have already shown sphingosine 1-phosphate receptor 1 (S1P1) modulators can improve outcomes in T-cell driven diseases such as multiple sclerosis and ulcerative colitis. Despite trailing those heavy hitters, Connect identified an opportunity to muscle in on the market, reckoning that it had a more potent modulator of S1P1 than its rivals and little to no activity against related receptors. 

The 145-subject phase 2 trial offered Connect a chance to make the case for CBP-307, but, at best, the results have muddied the waters, with a miss on the primary endpoint overshadowing more encouraging data on the secondary clinical remission measures.

After 12 weeks of daily oral dosing, Connect tracked a -2.65 change on adapted Mayo Score—which assesses stool frequency, rectal bleeding and endoscopy scores—in the high-dose CBP-307 arm versus a -2.01 shift in the placebo arm. The p-value came in at 0.103, causing the study to miss its primary endpoint. CBP-307 performed better on the full Mayo score, which includes a physician’s global assessment. That endpoint had a p-value of 0.05.

The complete Mayo score is one of a set of secondary endpoints that Connect presented as evidence that CBP-307 may work better than the primary fail suggests. Notably, Connect has evidence the drug candidate improves the rate of clinical remission.

In the high-dose cohort, 28.3% of participants went into clinical remission, when based on the adapted Mayo score. The clinical remission rate in the control group was 9.6%, resulting in a p-value of 0.016. Similarly, the rate of clinical remission based on the complete Mayo score was 18.9% in the CBP-307 group and 5.8% in the control arm.

Analysts at Jefferies compared the data favorably to the trial results of rival therapies, pointing out that CBP-307's secondary endpoint on clinical remission rate showed significant improvement on both the complete and adapted Mayo Scores when compared to placebo. "Safety looks largely in line with the same drug class,” the analysts wrote in a note to investors.

As Connect noted in its press release, the FDA has accepted clinical remission as a primary endpoint in clinical trials of other ulcerative colitis drugs. The Jefferies analysts said Connect thinks regulators may be amenable to switching endpoints for future studies or to going above the highest dose tested in the phase 2.

However, the biotech is looking to offload responsibility for further development, outlining plans to seek a partner to enable it to shift resources to its eczema and asthma prospect CBP-201.