CBP-307 is an orally available, next generation small molecule modulator of the sphingosine-1-phosphate 1 receptor (S1P1), a G-protein coupled receptor (GPCR) that plays a central role in regulating T cell movement and is a validated therapeutic target.
Ulcerative colitis (Phase 2)
Ulcerative colitis (UC) is a common form of inflammatory bowel disease (IBD) that causes chronic inflammation of the large intestine. The CDC estimates there are 3.1 million U.S. adults with a diagnosis of either Crohn’s disease or ulcerative colitis and as many as 80,000 US children who may have IBD, with most diagnoses made between 15 and 35 years of age.
Current treatment options include systemic corticosteroids and immunosuppressants, injectable biologics and surgery.3 While these treatments provide benefit, significant unmet need remains. We believe that CBP-307 has the potential to improve care outcomes for patients with UC by providing improved safety, efficacy and ease of administration compared with currently available therapies.
Crohn’s disease (Phase 2)
Crohn’s disease (CD) is an inflammatory bowel disease (IBD) that causes chronic inflammation of any site in the gastrointestinal tract, but most commonly affects the small intestine and beginning of the large intestine. According to the CDC, 3.1 million U.S. adults have a diagnosis of IBD.1 In North America, CD has a slightly lower prevalence than Ulcerative colitis, which is the other type of IBD. 2
Current treatment options include systemic corticosteroids as first-line therapy and a variety of biologics as second- and third-line therapy. 4 There is significant need for orally available therapies that can safely and effectively address unmet need for patients with Crohn’s disease, especially those with severe disease. 5
Mechanism of Action
S1P1 mediates the transit of T cells from lymph nodes into circulation and, as a result, the migration of T cells to tissues to release inflammatory mediators.6-10 CBP-307 causes T cells to internalize S1P1, trapping T cells inside the lymph nodes and preventing them from migrating to sites of inflammation.CBP-307 has high potency and selectivity11 and is designed to be the most potent modulator of the S1P1 drug class, if approved. CBP-307 has no significant activity for S1P3, a receptor subtype with known safety concerns, and significantly lower potency for S1P4 and S1P5 than S1P1.
Phase 1 Clinical Data
In a Phase 1 trial in healthy volunteers, dosing of 0.25 mg of CBP-307 in six healthy adults led to a 75% reduction in circulating lymphocytes at day 14. Once daily doses of up to 0.25 mg of CBP-307 were generally well-tolerated. Upon completion of dosing, the levels of lymphocytes returned to baseline within one week. This could minimize the period of being immunocompromised following CBP-307 treatment, potentially reducing the risk of patients developing infections.
Phase 2 Clinical Data
In a Phase 2 trial in adult patients with moderate-to-severe UC, dosing of 0.2 mg of CBP-307 showed a numerical improvement but did not achieve statistical significance. Once-daily doses of up to 0.2 mg of CBP-307 were generally well-tolerated. Upon completion of dosing, reductions in lymphocyte counts amongst individuals receiving CBP-307 0.2 mg confirmed pharmacodynamic activity of CBP-307 in patients with active UC. These top-line, induction phase data demonstrate the potential for CBP-307 to provide benefit to patients living with moderate-to-severe ulcerative colitis.
Current Development Status
CBP-307 was evaluated in a global Phase 2 clinical study in patients with moderate to severe ulcerative colitis. The top-line results at 12 weeks from its Phase 2 trial for CBP-307 warrant further clinical development. Connect plans to explore strategic partnerships to progress CBP-307 into future trials.
Posters & Publications
A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CPB-201AU002)
Presented at the the 29th European Academy of Dermatology and Venereology Congress (EADV), October 29, 2020
- Dahlhamer JM, Zammittie EP, Ward BW, et al. Prevalence of Inflammatory Bowel Disease Among Adults Aged >18 Years – United States, 2015. MMWR. 2016;65(42):1166-1169.
- Hanauer SB. Advances in IBD. Gastroentrerology & Hepatology. 2016;12(11):704-707
- Kobayahsi T, Siegmund B, Le Berre C, et al. Ulcerative Colitis. Nature Reviews: Disease Primers. 2020;6:74.
- Montiel-Martinez MP, Casis-Herce B, Masdeo-Gonzalez, et al. Pharmacologic Therapy for Inflammatory Bowel Disease Refractory to Steroids. Clinical and Experimental Gastroenterology. 2015;8:257-269.
- Crohn’s Disease: Dynamic Market Forecast to 2026 (GlobalData, October, 2018).
- Gilenya US PI. https://www.novartis.us/sites/www.novartis.us/files/gilenya.pdf
- Mayzent US PI. https://www.novartis.us/sites/www.novartis.us/files/mayzent.pdf
- Zeposia US PI. https://packageinserts.bms.com/pi/pi_zeposia.pdf
- Sandborn, W J et al. Ozanimod Induction and Maintenance treatment for Ulcerative Colitis. https://www.nejm.org/doi/full/10.1056/NEJMoa1513248
- Krause, A. et al. Modeling clinical efficacy of the S1P receptor modulator ponesimod in Psoriasis. Journal of Dermatological Science 89 (2018) 136–145
- Connect Biopharma CBP-307 Investigator Brochure (Ed. 5.0). January 2020 [Charter N. Potency and selectivity of CBP-307 on S1P receptors. DiscoveRx Corporation, California, 2015. Study No.: SCB001