About Connect Biopharma Holdings

Connect Biopharma Holdings Limited operates as a global clinical-stage biopharmaceutical company. The company is developing therapies for the treatment of T cell-driven inflammatory diseases. The company’s core expertise is in the use of functional cellular assays with T cells to screen and discover potent product candidates against immune targets. The company’s two most advanced clinical-stage programs include highly differentiated product candidates against validated targets. The company’s lead product candidate, CBP-201, is an antibody designed to target interleukin-4 receptor alpha, or IL-4Ra, which is a validated target for the treatment of inflammatory diseases, such as atopic dermatitis, or AD, and asthma. The company recently completed a Phase 2b trial of CBP-201 in the United States, Australia and New Zealand in adult patients with moderate-to-severe AD, in which primary and key secondary endpoints were met, and plans to initiate a global Phase 3 program in adult patients with moderate-to-severe AD in the second half of 2022. The company is conducting a Phase 2b trial evaluating CBP-201 in Type 2 inflammatory asthma and chronic rhinosinusitis with nasal polyps, or CRSwNP, and a pivotal trial in moderate-to-severe AD patients in the PRC. Furthermore, the company is developing CBP-307, a modulator of a T cell receptor known as sphingosine 1-phosphate receptor 1, or S1P1, for the treatment of inflammatory bowel disease, or IBD. Specifically, the company is developing CBP-307 for two types of inflammatory bowel disease (IBD), ulcerative colitis, or UC, and Crohn’s disease, or CD. The company anticipates reporting top-line results from a global Phase 2 trial in UC in the second quarter of 2022, while the company will determine whether to initiate further clinical trials in CD after evaluating the Phase 2 UC data. The company’s immune modulator product candidates originate from its approach to drug discovery based on using biologically relevant functional cellular assays to conduct primary drug screens instead of high-throughput biochemical assays. The clinical and preclinical results the company has observed for its product candidates support the potential for this physiologically relevant methodology to yield highly differentiated solutions, in a more efficient manner. The company’s approach is agnostic to drug modalities and has been used to identify both small molecule and antibody product candidates. The company is advancing CBP-201, an investigational anti-IL-4Ra antibody, for the treatment of inflammatory allergic diseases, such as AD, asthma and CRSwNP. Inhibition of IL-4Ra blocks the action of two inflammatory cytokines: interleukin- 4, or IL-4, and interleukin-13, or IL-13. In a randomized, double-blinded placebo-controlled Phase 2b trial in adult AD patients, the company observed significant improvements in primary and key secondary endpoints on skin clearance, disease severity, and itch, and CBP-201 was generally well-tolerated. CBP-307 is an investigational, small molecule modulator of S1P1, a regulator of T cell mobilization out of lymph nodes into the periphery. Inhibiting S1P1 leads to reduction in the levels of these T cells in circulation and a reduction in autoimmune-related inflammation. S1P1 is a validated therapeutic target with three drugs approved to treat multiple sclerosis: fingolimod, marketed as Gilenya by Novartis, siponimod, marketed as Mayzent by Novartis, and ozanimod, marketed as Zeposia, by Squibb. Evidence from third-party clinical trials suggests that the potential of S1P1 modulators is far broader than multiple sclerosis and includes highly prevalent diseases with unmet need, such as UC and CD, and Zeposia received approval for the treatment of adults with moderately to severely active UC from the FDA and EMA in 2021. The company is conducting a global Phase 2 trial in ulcerative colitis (UC) and anticipate reporting top-line results before the end of the second quarter of 2022. In addition, the company intends to initiate a global clinical trial in CD based on the preliminary clinical responses observed in a limited number of patients in an earlier CD clinical trial. The company is developing CBP-174, a peripherally acting, small molecule H3R antagonist, for oral administration to treat chronic itch associated with skin inflammation. The company has exclusively licensed global rights to CBP-174 from Arena Pharmaceuticals, Inc., or Arena, to complement its CBP-201 program in AD. The company’s preclinical mouse model study has indicated that CBP-174 led to reductions in scratching within the first 30 minutes of dosing, which could potentially translate to rapid reduction in pruritus in the clinic. The company expects to complete its Phase 1 dose escalation study with CBP-174 in healthy adults in the first half of 2022 and anticipates reporting top-line results in the first half of 2022. The company is building a rich pipeline of internally designed, wholly owned small molecules and antibodies targeting other aspects of T cell biology. The company is a global company with clinical development activities in the United States, the PRC, Europe, and Australia and operations in those geographies, as well as Hong Kong. The company applies its approach to develop product candidates against targets in T cell modulation related to inflammatory diseases with large unmet need. The company is advancing CBP-201, an investigational, an anti-IL-4Ra antibody, for the treatment of inflammatory allergic diseases such as AD, asthma and CRSwNP. Inhibition of IL-4Ra blocks the action of two inflammatory cytokines: IL-4 and IL-13. Dupilumab, marketed as Dupixent by Sanofi and Regeneron, an antibody that also targets IL-4Ra, has been demonstrated to lead to significant therapeutic benefit in patients with these diseases. CBP-201 is an investigational, human monoclonal antibody targeting IL-4Ra. As an inhibitor of IL-4Ra, CBP-201 blocks inflammatory signaling by both IL-4 and IL-13. CBP-201 binds to a region of IL-4Ra that is distinct from that bound by dupilumab and associated with high binding affinity and potency for IL-4Ra. The company’s clinical development program focuses on the potential for differentiating CBP-201 from dupilumab in the degree of clinical response and with less frequent dosing. The company has completed a Phase 2b trial of CBP-201 in adult patients with moderate-to-severe AD, that was conducted in 59 trial sites across the United States, the PRC, Australia and New Zealand, and was designed to assess efficacy, safety, pharmacokinetics and pharmacodynamics with longer term, alternate dosing schedules (CBP-201 WW001). The prolonged pharmacodynamic TARC response following a single dose of CBP-201 observed in the company’s initial Phase 1a trial suggests that it may be possible to achieve suppression of IL-4Ra on a once every two weeks or once every four weeks dosing schedule, following a loading dose. The company initiated a PRC-specific pivotal trial to evaluate CBP-201 in adult patients with moderate-to-severe AD, in the second half of 2021. The company initially designed the trial to enroll 255 patients, but have decided to expand the trial to include a target enrollment of approximately 500 patients. The company is conducting clinical trials to assess the potential of CBP-201 in other diseases driven by dysregulation of the Th2 immune response, including global Phase 2 trials of CBP-201 in patients with Type 2 inflammatory asthma and CRSwNP, both of which were initiated in 2021. CBP-307 is an investigational, selective modulator of sphingosine 1-phosphate receptor 1, or S1P1, which the company is developing for the treatment of UC and CD. The company has observed in vitro potency, selectivity and pharmacokinetics for CBP-307. The company’s Phase 2 trial in CD ended early in 2021 due to COVID-19 enrollment challenges. CBP-307 is an orally available, next generation, small molecule modulator of S1P1 that is designed to reduce inflammation without killing T cells or targeting a specific cytokine. By design, CBP-307 is highly selective for S1P1 without significant activity for S1P2 and S1P3 receptor subtypes allowing it to potentially have an optimized effect on circulating T lymphocytes. The company discovered CBP-307 by running a functional screen for the desired biological property, which in this case was the ability of a small molecule to cause internalization of S1P1 from its native location on the surface of T cells. CBP-307 is a highly potent and selective modulator of S1P1, which in preclinical studies has shown selectivity of over 80,000-fold in S1P1 versus S1P3. The company has completed a Phase 1 trial of CBP-307 in 44 healthy adults in Australia, which consisted of a 7-day single ascending dose regimen and a 28-day multiple ascending dose regimen, and another in 30 healthy adults in the PRC. The company has initiated and fully enrolled a double-blind, placebo-controlled global Phase 2 trial of CBP-307 in 134 adult patients with moderate-to-severe UC. In parallel, the company initiated a Phase 2 trial of CBP-307 in patients with moderate-to-severe CD in the PRC. The company is developing CBP-174 as a rapid acting therapy for the alleviation of pruritus in AD. CBP-174 is an antagonist of histamine receptor 3, or H3R, that was observed to reduce scratching after injection in a mouse model of pruritus. The company obtained global rights to CBP-174 from Arena Pharmaceuticals, Inc. (Arena). The company initiated a Phase 1 trial with CBP-174 in the first half of 2021 and expects to have topline results in first half of 2022. The company is developing CBP-174, a peripherally acting H3R antagonist, for oral administration to treat chronic pruritus associated with skin inflammation. The company has developed a topical 0.01% ointment formulation of CBP-174 that led to similar reductions in scratching frequency in these mice. The company observed that the slow release of CBP-174 from the topical ointment led to prolonged exposure while simultaneously increasing the local concentration of drug at skin lesions. The company initiated a Phase 1 trial of CBP-174 in the first half of 2021. The company enrolled six cohorts of eight volunteers with six in each cohort receiving one of six oral doses of CBP-174 and two placebo. The primary endpoints of this trial are safety and tolerability, as well as pharmacokinetics changes. The company owns or exclusively license more than 50 issued U.S. or foreign patents and have more than 60 pending patent applications in multiple jurisdictions, including in the United States, the PRC, the United Kingdom, France, Germany, Switzerland, the Netherlands, Sweden, Spain, Belgium, Italy, Japan, Australia, and Hong Kong. These issued patents and patent applications include: With respect to the composition of matter of CBP-201, the company has a patent family with an issued U.S. patent, issued foreign patents, including in the PRC, and pending patent applications in various jurisdictions, where the issued patents and the patent applications, if issued, are expected to expire between 2036 and 2037, without accounting for any available patent term adjustments or extensions. The company also has two other patent families that relate to its CBP-201 program, which include pending patent applications in various jurisdictions, including in the United States, where the patent applications, if issued, are expected to expire between 2039 and 2041, without accounting for any available patent term adjustments or extensions. With respect to the composition of matter of CBP-307, the company has a patent family that includes issued U.S. and foreign patents, including in the PRC, and pending patent applications in various jurisdictions, where the issued patents and the pending patent applications, if issued, are expected to expire between 2033 and 2034, without accounting for any available patent term adjustments or extensions. The company further has one issued patent in the PRC, and pending U.S. and foreign patent applications, related to additional salts and crystal forms of CBP-307, where the issued patent and the patent applications, if issued, are expected to expire between 2037 and 2038, without accounting for any available patent term adjustments or extensions. With respect to the composition of matter of CBP-174 and methods of making and using the same, the company has issued U.S. and foreign patents, including in the PRC, where the patents and pending patent applications, if issued, are expected to expire in 2034, without accounting for any available patent term adjustments or extensions, which it exclusively licensed from Arena. In June 2012, the company and Arena entered into an exclusive license agreement, or the Arena Agreement. Pursuant to the Arena Agreement, as subsequently amended, Arena granted it an exclusive (even as to Arena, except for internal research purposes), worldwide, royalty-bearing, sublicensable (subject to some conditions) license to identify, research, develop, make, have made, use, sell, offer for sale, have sold and import products under some patents and know how relating to H3R antagonists and methods of making and using such H3R antagonists. Strategy The key elements of the company’s strategy are to discover and develop product candidates targeting inflammatory diseases with significant unmet medical need; continue development of its three most advanced product candidate; advance its earlier stage programs and continue to invest in R&D to expand and enhance its pipeline; and leverage its core strengths in the United States and the PRC and expand its operations globally. Research and Development Expenses The company’s research and development (R&D) expenses included RMB 518.0 million (USD 81.2 million) for the year ended December 31, 2021. Government Regulation and Product Approval As a biopharmaceutical company with operations in the United States, the company is subject to extensive regulation. Among others, the FDA, the EMA, U.S. Department of Health and Human Services Office of Inspector General, the Centers for Medicare and Medicaid Services, or CMS, and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing and distribution of drugs and biologics, such as those it is developing. History Connect Biopharma Holdings Limited was founded in 2012. The company, a Cayman Islands exempted company, was incorporated in 2015.