TAICANG, SUZHOU, China, May 6, 2019 /PRNewswire/ -- Connect Biopharma today announced that it has successfully completed a phase 1 single ascending dose (SAD) study of its novel IL-4Rα antibody, CBP-201. The randomized, double-blind, placebo-controlled study, conducted in Melbourne, Australia, evaluated the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CBP-201 in 40 healthy adults. CBP-201 was administered by subcutaneous (SC) injection (75 mg, 150 mg, 300 mg, 600 mg) or intravenously (300 mg).
In this study CBP-201 demonstrated rapid and sustained immune modulation activity after a single dose. Significant reduction in serum levels of thymus activation and regulated chemokine (TARC/CCL17), a biomarker elevated in atopic dermatitis and other Th2 inflammatory diseases, was observed across all five dose groups (p<0.001 vs. placebo). On average, the decrease in serum TARC occurred as early as Day 3 and was maintained through Day 42 post dosing.
High and sustained serum CBP-201 concentrations were achieved with the expected greater than dose-proportional exposure. Bioavailability was 89% for the 600 mg SC dose. At the 300 mg SC and 600 mg SC doses, serum CBP-201 concentrations on Day 56 were well above the drug concentrations that achieved full blockade of IL-4Rα in human peripheral blood mononuclear cells (PBMC).
CBP-201 was very well tolerated. No serious adverse event (SAE) was observed at any dose level through 12 weeks of post-treatment follow-up (final study visit). Treatment emergent adverse events (AE) occurred in 80% and 70% of subjects who received CBP-201 and Placebo, respectively, and were all mild to moderate in intensity. Treatment related AEs occurred in 36.7% and 60% of subjects who received CBP-201 and Placebo, respectively. The most common AEs were headache, dizziness, and upper respiratory tract infection.
"We are extremely pleased that CBP-201 exhibited excellent tolerability along with potent biomarker activity in this first-in-human study. The prolonged biomarker activity after a single dose is consistent with a favorable PK profile and high potency," commented Jeffery White, MD., Chief Medical Officer of Connect Biopharma. "We believe the PK and PD data support the potential for once every four weeks dosing which will be of significant benefit to patients and caregivers and we look to confirm this more convenient dosing regimen in future trials. We have initiated a Phase 1b study in patients with moderate to severe atopic dermatitis with topline data anticipated in Q4 2019."
"We are thrilled that another drug candidate that emerged from our Immune Modulation Technology Platform has shown potent and sustained biomarker activity in the clinical setting," added Dr. Zheng Wei, co-founder and CEO of Connect Biopharma. "CBP-201 blocks a central pathway of Th2 inflammation by suppressing the activities of both IL-4 and IL-13. Abundant preclinical and clinical studies showed that simultaneous blockade of both IL-4 and IL-13 has the strongest effect on an array of Th2 inflammatory diseases. Our data continue to demonstrate that CBP-201 has the potential to be best in class and support our plan to move forward aggressively with its clinical development."
CBP-201 is an extremely potent monoclonal antibody against IL-4Rα. IL-4Rα is a cell surface protein required for the signaling of both IL-4 and IL-13, two key Th2 pro-inflammatory cytokines with significant overlapping biological activities. CBP-201 blocks IL-4Rα signaling induced by IL-4 and IL-13 with an IC50 of 38.2 pM and 45.8 pM, respectively. CBP-201 inhibits TF-1 cell proliferation induced by IL-4 and IL-13 with an IC50 of 55.6 pM and 67.4 pM, respectively. CBP-201 was discovered internally using Connect Biopharma's Immune Modulation Technology Platform, and is under clinical development to treat atopic dermatitis and other Th2 inflammatory diseases with high unmet needs.
About Connect Biopharma
Connect Biopharma is a China-based global clinical-stage company focused on discovery and development of novel immune modulators for the treatment of autoimmune diseases and inflammation. Our Immune Modulation Technology Platform is a high-throughput screening platform built on the biology of T cell function, which rapidly identifies molecules that target clinically-validated disease pathways.
Our lead drug candidate is CBP-307, an orally-active, next-generation S1P1 and S1P5 (a G-protein coupled receptor-GPCR) modulator for the treatment of a range of autoimmune disorders, including inflammatory bowel disease, psoriasis, multiple sclerosis and other autoimmune diseases. We have completed two phase 1 randomized, double-blind, placebo-controlled studies that assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of CBP-307. In these studies, CBP-307 exhibited an excellent safety profile and potent T cell modulation activity as well as optimal pharmacokinetic and pharmacodynamic profiles, demonstrating best-in-class potential. Two phase 2 studies are currently underway to evaluate the efficacy and safety of CBP-307 in patients with moderate-to-severe ulcerative colitis and moderate-to-severe Crohn's disease.
Our second drug candidate is CBP-201, a novel monoclonal antibody that targets IL-4Rα, a receptor subunit required for IL-4 and IL-13 signaling, and blocks a central pathway in Th2 inflammation. CBP-201 is in clinical development for the treatment of atopic dermatitis and other allergic inflammatory diseases.
Additional immune modulators in our pipeline include CBP-174, CBP-233, and CBP-312. For more information about our pipeline, please visit www.connectbiopharm.com
SOURCE Connect Biopharmaceuticals