icanbelimod (CBP-307) / Suzhou Connect Biopharma - LARVOL DELTA

Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia. (PubMed, Front Immunol) - P1 | "Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts. ClinicalTrials.gov, identifier NCT02280434.b."

Clinical • Journal • PK/PD data • Cardiovascular • Pain • S1PR1

Fine-tuning activation specificity of G-protein-coupled receptors via automated path searching. (PubMed, Proc Natl Acad Sci U S A) - "In particular, the revealed transition state structures pointed out toward two S1PR3 residues F263/I284, that dictate the preference of existing agonists CBP307 and BAF312 on S1PR1/5. BRET assays confirmed that both chiral forms activate S1PR1 at nanomolar concentration, 1 to 2 orders of magnitude less than those for S1PR3/5. Collectively, these results signify the promise of our approach in fine agonist design for G-protein-coupled receptors."

Journal • S1PR1

Efficacy and Safety of Icanbelimod (CBP-307) in Adults With Moderate to Severe Ulcerative Colitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial (AIBD 2023) - P2 | "In this dose-ranging Phase 2 trial, icanbelimod significantly improved key outcomes, including complete Mayo score, clinical response and clinical remission (a key FDA regulatory endpoint) at Week 12 and sustained clinical remission, through Week 48 in patients who achieved clinical remission following 12 weeks of induction therapy. Icanbelimod was well tolerated. Further investigation of optimal doses is warranted to better enhance therapeutic response."

Clinical • P2 data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

New Data Positive for Icanbelimod as a Ulcerative Colitis Treatment (HCPLive) - "'Current treatment options for UC have not demonstrated break-through efficacy based on clinical remission, highlighting the need for new and more effective therapies. Based on the icanbelimod 0.2 mg data, the clinical remission efficacy, safety data and absolute lymphocyte count reduction are compelling,' said Brian Feagan...in a statement."

Media quote

Connect Biopharma Announces Positive Long-Term Data from the Maintenance Period Through Week 48 of CN002 Phase 2 Icanbelimod Trial in Patients with Moderate-to-Severe Ulcerative Colitis (GlobeNewswire) - P2 | N=145 | NCT04700449 | Sponsor: Suzhou Connect Biopharmaceuticals, Ltd. | "Connect Biopharma Holdings Limited...announced positive data at Week 48 from Phase 2 trial (CN002) for icanbelimod (formerly known as CBP-307), a once-daily, orally administered, selective sphingosine 1-phosphate receptor 1 (S1P1) modulator in development for the treatment of ulcerative colitis (UC)....86% (18/21) of patients who received icanbelimod completed the maintenance period. 67% (12/18) of patients who completed the study through Week 48 achieved clinical remission. 80% (8/10) of patients who achieved clinical remission at the end of the induction period sustained it through Week 48. Overall, 57% (12/21) of patients with clinical response at the end of the induction period achieved clinical remission at the end of the maintenance period....Icanbelimod was well-tolerated and long-term safety data through Week 48 remained consistent with safety findings observed in the induction period."

P2 data • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Connect Biopharma Reports Full Year 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Results of the Phase 2 maintenance portion of the trial are expected to be reported in the second quarter of 2023 and the Company is seeking strategic partnerships to progress CBP-307 into future trials in UC and Crohn’s disease....R&D expenses for the year ended December 31, 2022 totaled RMB 652.2 million (USD 93.7 million), compared with RMB 518.0 million (USD 81.2 million) for the year ended December 31, 2021, primarily due to increased third-party clinical trial costs related to advancing the clinical development of the Company’s lead product candidates. This includes...ongoing global Phase 2 trial costs for CBP-307 in UC, as well as higher personnel costs for additional R&D headcount."

Commercial • P2 data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=145 | Completed | Sponsor: Suzhou Connect Biopharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

Trial completion • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Connect Biopharma Provides Business and Clinical Development Program Update (GlobeNewswire) - "CBP-307 Phase 2 trial in moderate-to-severe Ulcerative Colitis (UC): The Company also anticipates completing the global Phase 2 maintenance phase for CBP-307 in the first half of 2023....The Company is actively seeking to out-license CBP-307 for future trials in UC and Crohn’s disease to capitalize on its potential to be a competitive asset and a welcome addition to the gastroenterologist’s treatment armamentarium."

P2 data • Trial completion • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Connect Biopharma Reports First Half 2022 Financial Results and Provides Business Update (Yahoo Finance) - "CBP-307 in UC: On track to complete Phase 2 maintenance phase by the end of 2022....R&D expenses increased to RMB 340.8 million (USD 50.8 million) for the six months ended June 30, 2022, from RMB 217.8 million for the six months ended June 30, 2021. This increase was driven primarily by higher clinical trial-related expenses for CBP-201, including expenses related to advancing CBP-201 for AD in China, and ongoing global Phase 2 trial costs for CBP-201 in asthma, and global Phase 2 trial costs for CBP-307 in UC, as well as higher personnel costs for additional R&D headcount."

Commercial • P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Connect Biopharma Announces Week 12 Top-Line Results from Phase 2 CBP-307 Trial in Patients with Moderate-to-Severe Ulcerative Colitis (GlobeNewswire) - P2 | N=145 | NCT04700449 | Suzhou Connect Biopharmaceuticals |'"Ulcerative colitis is a serious chronic condition with continued unmet need. The overall 12-week results for CBP-307 demonstrate the therapeutic potential to induce a significant treatment response consistent with clinical data of other S1P modulators in patients with UC,' said David T. Rubin, MD..."

Media quote • P2 data

Connect Biopharma Announces Week 12 Top-Line Results from Phase 2 CBP-307 Trial in Patients with Moderate-to-Severe Ulcerative Colitis (GlobeNewswire) - P2 | N=145 | NCT04700449 | Suzhou Connect Biopharmaceuticals | "The primary endpoint of LS mean change from baseline in adapted Mayo Score (stool frequency, rectal bleeding, and endoscopy scores) at Week 12 for CBP-307 0.2 mg and placebo were -2.65 and -2.01, respectively (p=0.103). Secondary endpoints that were met for CBP-307 0.2 mg included a significantly higher proportion of patients reaching Clinical Remission compared to placebo as measured by both adapted (28.3% vs 9.6%, difference=18.7; p=0.016) and complete Mayo Scores (18.9% vs 5.8%, difference=13.1; p=0.044), respectively."

P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=145 | Active, not recruiting | Sponsor: Suzhou Connect Biopharmaceuticals, Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2022 ➔ Dec 2022

Enrollment closed • Trial completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Structural insights into sphingosine-1-phosphate receptor activation. (PubMed, Proc Natl Acad Sci U S A) - "Phosphorylated Fingolimod [(S)-FTY720-P] could modulate lymphocyte trafficking and treat multiple sclerosis. The nonlipid-like agonist CBP-307 is currently being evaluated in a global phase 2 clinical study in moderate to severe ulcerative colitis and Crohn's disease. Meanwhile, two binding poses of CBP-307 and the unoccupied subpocket we observed may provide opportunities to improve further the efficacy and specificity of CBP-307 targeting different S1P receptors."

Journal • CNS Disorders • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis • Ulcerative Colitis

A Study to Investigate the Effects of CBP-307 on the Heart Rate-corrected QT Interval (QTc) in Healthy Subjects (clinicaltrials.gov) - P1 | N=112 | Completed | Sponsor: Connect Biopharma Australia Pty Ltd | Recruiting ➔ Completed | N=68 ➔ 112 | Trial completion date: Aug 2022 ➔ Mar 2022

Enrollment change • Trial completion • Trial completion date • Immunology

A Study On Human Mass Balance And Biotransformation (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Suzhou Connect Biopharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

Trial completion

Connect Biopharma Reports Full Year 2021 Financial Results and Provides Business Update (Yahoo Finance) - "Topline Phase 2 CBP-307 Results in Moderate-to-Severe Ulcerative Colitis Expected to Be Reported in H1 2022...Research and development expenses increased to RMB 518.0 million (USD 81.2 million) for the year ended December 31, 2021, from RMB 150.9 million in the year ended December 31, 2020. This increase was driven primarily by higher clinical trial related expenses for...the initiation of a global Phase 2 trial for CBP-307 in UC and Crohn’s Disease (CD) indications."

Commercial • P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=134 | Recruiting | Sponsor: Suzhou Connect Biopharmaceuticals, Ltd. | Trial primary completion date: Dec 2021 ➔ Mar 2022

Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Investigate the Effects of CBP-307 on the Heart Rate-corrected QT Interval (QTc) in Healthy Subjects (clinicaltrials.gov) - P1 | N=68 | Recruiting | Sponsor: Connect Biopharma Australia Pty Ltd | Trial completion date: Feb 2022 ➔ Aug 2022 | Trial primary completion date: Dec 2021 ➔ Jun 2022

Trial completion date • Trial primary completion date • Immunology

A Study On Human Mass Balance And Biotransformation (clinicaltrials.gov) - P1; N=8; Active, not recruiting; Sponsor: Suzhou Connect Biopharmaceuticals, Ltd.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Connect Biopharma Completes Enrollment of CBP-307 Global Phase 2 Clinical Trial in Moderate-to-Severe Ulcerative Colitis (GlobeNewswire) - "Connect Biopharma Holdings Limited...announced that it has completed full enrollment of the phase 2 clinical trial evaluating CBP-307 in adult patients with moderate-to-severe Ulcerative Colitis (UC)...'We look forward to announcing topline results of the 12-week induction phase of this trial by the end of the first quarter of 2022.'"

Enrollment closed • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study On Human Mass Balance And Biotransformation (clinicaltrials.gov) - P1; N=8; Recruiting; Sponsor: Suzhou Connect Biopharmaceuticals, Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study On Human Mass Balance And Biotransformation (clinicaltrials.gov) - P1; N=8; Not yet recruiting; Sponsor: Suzhou Connect Biopharmaceuticals, Ltd.

Clinical • New P1 trial

Connect Biopharma Provides Business Update and Reports First Half 2021 Financial Results (GlobeNewswire) - "Anticipated Upcoming Milestones...Anticipate reporting the global CBP-307 phase 2b top-line data evaluating ulcerative colitis (UC) in the first quarter of 2022."

P2b data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Investigate the Effects of CBP-307 on the Heart Rate-corrected QT Interval (QTc) in Healthy Subjects (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: Suzhou Connect Biopharmaceuticals, Ltd.; Active, not recruiting ➔ Recruiting

Enrollment open • Immunology

A Study to Investigate the Effects of CBP-307 on the Heart Rate-corrected QT Interval (QTc) in Healthy Subjects (clinicaltrials.gov) - P1; N=64; Active, not recruiting; Sponsor: Suzhou Connect Biopharmaceuticals, Ltd.; Not yet recruiting ➔ Active, not recruiting; Trial completion date: Oct 2021 ➔ Feb 2022

Clinical • Enrollment closed • Trial completion date • Immunology