Core Viewpoint - Connect Biopharma's collaborator, Simcere Pharmaceutical, has submitted a New Drug Application for rademikibart to treat atopic dermatitis in China, indicating significant progress in the development of this potential best-in-class therapy for inflammatory diseases [1][2]. Company Overview - Connect Biopharma is a clinical-stage biopharmaceutical company focused on developing innovative therapies for inflammatory diseases, with rademikibart as its lead product candidate targeting IL-4Rα [6]. - Simcere Pharmaceutical is an R&D-driven company focusing on therapeutic areas such as neuroscience, anti-oncology, autoimmune, and anti-infection [5]. Product Development - Rademikibart is a fully human monoclonal antibody that targets IL-4Rα, blocking the Th2 inflammatory pathway, which is relevant for treating atopic dermatitis and asthma [4]. - The AD market in China presents a considerable opportunity, with an estimated 70 million patients suffering from the condition [3]. Collaboration Agreement - In 2023, Connect Biopharma and Simcere entered an exclusive license and collaboration agreement for rademikibart in Greater China, granting Simcere exclusive rights for development, manufacturing, and commercialization [2][3]. - Connect Biopharma is eligible for milestone payments totaling approximately $110 million and tiered royalties on net sales in Greater China [3].

Rademikibart Clinical Development and Market Opportunity - Rademikibart shows the largest improvement in FEV observed with a biologic in asthma patients, with a 312 mL increase at 1-week and 420 mL at 24-weeks in patients with baseline eosinophils ≥300 cell/µL[9] - Market research indicates that acute exacerbation indications in asthma and COPD differentiate rademikibart from dupilumab and other biologics, potentially leading to greater chronic use[7, 9] - Projected worldwide peak sales for rademikibart with acute and chronic indications are >$3 billion for asthma and >$2 billion for COPD[7, 9, 25] - Connect has initiated parallel Phase 2 studies in asthma and COPD patients experiencing acute exacerbations, with data expected in 1H2026 and cash runway into 2027[7, 9, 11, 74] Rademikibart Differentiation and Efficacy - Rademikibart is a next-generation anti-IL-4Rα antibody with potential for less frequent dosing, greater sustained efficacy data, and faster onset observed in asthma trials[6, 27] - Home daily lung function data demonstrated 73% of FEV1 improvement seen on Day 7 was observed by Day 1, with 113% by Day 2[41, 42] - In a Phase 2b study, rademikibart significantly improved lung function at Week 12, with enhanced efficacy over placebo in high eosinophil patients (baseline ≥150 cells/µL)[47, 48] - Analysis of COPD-like patients from the global Phase 2b asthma study showed FEV1 change from baseline of 285 mL with Rademikibart 150 mg and 694 mL with Rademikibart 300 mg in all EOS levels[53] Financial Position and Exclusivity - The company has cash, cash equivalents, and short-term investments of $83995000 as of March 31, 2025, expected to support planned operations into 2027[74, 75] - Rademikibart exclusivity extends through at least 2040, supporting substantial growth and value creation[9, 67, 68]

Core Insights - Rademikibart has shown significant improvements in lung function and asthma control for patients with eosinophilic-driven type 2 asthma [1][2] - The treatment has led to a reduction in annualized exacerbation rates in the same patient group [1][10] - Ongoing Phase 2 studies for acute exacerbations in asthma and COPD are expected to report topline data in the first half of 2026 [1] Company Overview - Connect Biopharma is a clinical-stage biopharmaceutical company focused on asthma and COPD treatment [6] - The company is advancing rademikibart, a next-generation anti-interleukin-4-receptor alpha (IL-4Rα) antibody [6] - Rademikibart targets acute exacerbations, addressing a significant unmet need among asthma and COPD patients [6] Clinical Data Highlights - In a Phase 2b trial, rademikibart improved prebronchodilator forced expiratory volume in one second (FEV1) within one week, sustained through 24 weeks [3] - The treatment showed greater improvement in patients with elevated baseline eosinophil counts compared to the overall population [3] - Rademikibart demonstrated a 63% reduction in annualized asthma exacerbation rates (AAER) in patients with elevated eosinophils, 69% in those with elevated FeNO, and 74% in patients with both markers [10]

Summary of Connect Biopharma Holdings (CNTB) Conference Call Company Overview - Connect Biopharma Holdings (CNTB) is undergoing a transformation referred to as "Connect 2.0" with a new management team focused on drug development and regulatory activities [3][4] - The lead program is retimicobart, a next-generation IL-4 receptor alpha monoclonal antibody, positioned as a second-generation alternative to Dupixent [3][4] Core Product Insights - Retimicobart shows a significant improvement in FEV1, a key measure of airway function, with one of the largest improvements seen in biologics for asthma trials [4][5] - The onset of effect occurs within 24 hours, allowing for evaluation in acute settings rather than traditional chronic studies [5][6] - There are over 1 million asthma and 1.3 million COPD patients visiting ERs annually due to acute exacerbations, indicating a substantial market opportunity [5][9] Market Opportunity - Current biologics do not have indications for acute exacerbations, creating a "white space" for retimicobart [6][22] - Market research indicates that the novel acute indication could drive significant chronic use, with a preference share of 40%-45% for acute use and 75% for chronic treatment following acute administration [10][22] - The product is expected to have a multi-billion dollar commercial potential with both acute and chronic indications [23][30] Clinical Development - Two parallel trials (cbreeze stat) for asthma and COPD are underway, with data expected in the first half of the following year [15][16] - The acute studies are designed to assess improvements in FEV1 and reduce hospitalization rates, with a focus on cost savings for hospitals [16][30] - The company has received FDA clearance to move into phase three for atopic dermatitis, pending completion of a partner study in China [21][24] Financial Considerations - Development costs for acute indications are estimated at around $50 million, while combined acute and chronic programs could reach $200 million [29] - The company has sufficient cash reserves to execute its plans into 2027, allowing for strategic development without immediate dilution [24][30] Regulatory Landscape - There is no precedent for acute indications in the biologics market, presenting both challenges and opportunities for Connect Biopharma [33] - Extensive discussions with the FDA have provided insights into potential pathways for approval [33] Conclusion - Connect Biopharma is positioned to leverage its innovative product retimicobart in a largely untapped market for acute asthma and COPD treatment, with a strong focus on rapid clinical development and strategic partnerships to enhance its market presence [22][30]

Summary of Connect Biopharma Holdings (CNTB) Conference Call - June 04, 2025 Company Overview - Connect Biopharma is undergoing a transformation referred to as "Connect 2.0" with a new management team experienced in drug development and public biotech operations [2][22] - The company is focusing on retimicobart, a second-generation IL-4 receptor alpha monoclonal antibody, targeting asthma and COPD [2][3] Key Developments - Two parallel Phase II studies have been initiated for retimicobart, specifically addressing acute exacerbations in asthma and COPD [2][3] - The company has sufficient cash to fund these studies, with a runway extending into 2027 [3][22] - The headquarters has been relocated to San Diego, reducing the company's footprint in China to become more U.S.-centric [3] Market Opportunity - Market research indicates that having an acute indication for retimicobart could create a market opportunity exceeding $5 billion globally [4] - There are over 2 million emergency department visits annually in the U.S. for asthma and COPD exacerbations, highlighting a significant patient population [5][8] - Current treatments for acute exacerbations are largely unchanged from two decades ago, primarily involving steroids and bronchodilators, which take hours to stabilize patients [24][25] Product Differentiation - Retimicobart is positioned uniquely as no other biologic currently has an acute indication for asthma or COPD [4][6] - The product has shown rapid onset of action, with over 70% of the benefit observed within 24 hours of administration [5][13] - The company aims to reduce emergency room visits and hospitalizations, potentially shortening hospital stays and providing cost savings for healthcare systems [28][29] Clinical Data - Previous Phase II studies indicated significant improvements in respiratory function (FEV1) with retimicobart, showing an average improvement of 420 ml at 24 weeks [4][12] - The product demonstrated a rapid improvement in airway function, with 73% of the benefit observed within 24 hours [13][16] - The company has a differentiated safety profile compared to Dupixent, particularly in patients with high eosinophil counts [17][20] Financial Position - As of March, the company reported a cash position of nearly $84 million, sufficient to fund ongoing Phase II programs [22] - The exclusivity for retimicobart extends well into 2040, providing a long-term competitive advantage [20] Future Catalysts - Results from the two Phase II trials are expected in the first half of next year, with ongoing preclinical data supporting the product's differentiation [33][32] - The company is also developing a separate product for hospital use to enhance economic viability and fit within existing reimbursement structures [30] Conclusion - Connect Biopharma is strategically positioned to address significant unmet needs in the treatment of acute asthma and COPD exacerbations, with a strong focus on rapid onset of action and cost-effectiveness for healthcare providers [28][29][30]

Core Insights - Connect Biopharma Holdings Limited is a clinical-stage biopharmaceutical company focused on transforming care for asthma and chronic obstructive pulmonary disease (COPD) [1][3] - The company announced two oral presentations at the European Academy of Allergy and Clinical Immunology (EAACI) 2025 Annual Congress, highlighting the efficacy of its drug Rademikibart in treating eosinophilic driven, Type 2 asthma [1][2] Company Overview - Connect Biopharma is headquartered in San Diego, California, and is dedicated to advancing Rademikibart, a next-generation anti-interleukin-4-receptor alpha (IL-4Rα) antibody [3] - The company targets acute exacerbations in asthma and COPD, addressing a significant unmet need among approximately 1 million asthma patients and 1.3 million COPD patients in the U.S. who experience acute exacerbations annually [3] Clinical Trial Highlights - Rademikibart demonstrated strong efficacy and safety data in a Phase 2 trial for asthma, showing clinically meaningful reductions in exacerbations [3] - Rapid, statistically significant improvements in forced expiratory volume in one second (FEV1) were observed within one week, and in most cases, within 24 hours via home spirometry [3] Presentation Details - The presentations at the EAACI Congress will cover the reduction in annualized exacerbations and improvement in lung function with Rademikibart in eosinophilic driven, Type 2 asthma [2]

Company Overview - Connect Biopharma Holdings Limited is a clinical-stage biopharmaceutical company focused on transforming care for asthma and chronic obstructive pulmonary disease (COPD) [3] - The company is headquartered in San Diego, California and is advancing rademikibart, a next-generation anti-interleukin-4-receptor alpha (IL-4Rα) antibody [3] - Rademikibart targets acute exacerbations in asthma and COPD, addressing significant unmet needs among approximately 1 million asthma patients and 1.3 million COPD patients in the U.S. who experience acute exacerbations annually [3] Clinical Development - In a Phase 2 trial for asthma, rademikibart demonstrated strong efficacy and safety data, showing clinically meaningful reductions in exacerbations and rapid improvements in forced expiratory volume in one second (FEV1) [3] - Improvements in FEV1 were observed within one week, and in most cases, within 24 hours via home spirometry [3] Upcoming Events - Company management will participate in the Noble Capital Markets Virtual Conference on June 4, 2025, at 9:00 a.m. ET [1] - The Jefferies Healthcare Conference will take place on June 5, 2025, at 7:35 a.m. ET, with a live webcast available on the company's website [2]

Core Insights - Connect Biopharma's rademikibart shows significant improvement in airway function (FEV1) within 24 hours and reduces acute exacerbations in asthma and COPD patients, supporting ongoing Phase 2 studies expected to report data in 1H26 [1][2] - Rademikibart demonstrates differentiated structural and molecular dynamics with enhanced IL-4Rα inhibition compared to dupilumab, providing a basis for its superior efficacy and safety profile [1][8] Group 1: Clinical Data - Rademikibart rapidly improves lung function (FEV1) during the first week of treatment, with most improvement observed within 24 hours [3] - Patients with elevated eosinophil counts (≥300 cells/µL) showed the greatest improvements in lung function and significant reduction in acute exacerbations [3] - In a post-hoc analysis, rademikibart significantly improved prebronchodilator FEV1 over 24 weeks, particularly in patients with eosinophilic-driven COPD [3] Group 2: Safety and Efficacy - Rademikibart treatment groups had lower proportions of patients with high post-baseline eosinophil counts compared to dupilumab, indicating a differentiated safety profile [8] - Mean eosinophil counts decreased by approximately 30% at Week 24 for rademikibart, while dupilumab treatment groups experienced increases between 50% and 120% [8] - Structural analysis revealed rademikibart's optimized binding to IL-4Rα, enhancing its efficacy compared to dupilumab [8] Group 3: Company Overview - Connect Biopharma is focused on transforming care for asthma and COPD, with rademikibart positioned as a potentially best-in-class anti-IL-4Rα antibody [5] - The company targets a significant unmet need in acute exacerbations, with approximately 1 million asthma and 1.3 million COPD patients in the U.S. experiencing such events annually [5] - Rademikibart has shown strong efficacy and safety data in Phase 2 trials, with rapid improvements in FEV1 observed within one week [5]

Financial Performance - For the three months ended March 31, 2025, research and development expense was $6.6 million, a decrease of 23.4% from $8.7 million in the same period in 2024[103]. - General and administrative expense increased to $4.8 million for the three months ended March 31, 2025, compared to $4.0 million for the same period in 2024, primarily due to increased professional fees and personnel costs[104]. - The net loss for the three months ended March 31, 2025, was $10.3 million, or $0.19 per share, compared to a net loss of $8.7 million, or $0.16 per share, for the same period in 2024[108]. - Cash, cash equivalents, and short-term investments totaled $84.0 million as of March 31, 2025, sufficient to meet anticipated cash requirements for at least one year[107]. - Net cash used in operating activities for the three months ended March 31, 2025, was $10.0 million, significantly higher than $0.6 million for the same period in 2024[109]. - Net cash used in investing activities for the three months ended March 31, 2025, was $20.6 million, compared to net cash provided by investing activities of $9.3 million for the same period in 2024[110]. Clinical Trials and Product Development - The company announced positive data from a Phase 2 trial of rademikibart, indicating its potential as a treatment for asthma with rapid onset of action and significant reductions in exacerbation rates[96]. - The first patient was enrolled in the Phase 2 clinical trial for rademikibart in patients experiencing acute exacerbations of asthma or COPD, with primary endpoints focused on treatment failure over 28 days[98][99]. Corporate Changes and Challenges - The company relocated its corporate headquarters to a new location in San Diego, California, with an operating lease that increases from $0.3 million to $0.4 million over the lease term[113]. - The company faces potential challenges from high inflation rates and economic uncertainty, which may impact operating costs and access to financing[119]. - The company faces challenges in raising capital due to unfavorable global economic and political conditions, which may impact research and development programs[120]. - The company is experiencing stress on working capital resources due to worsening global macroeconomic conditions and wage increases[121]. - Future commercialization efforts may be delayed or reduced if capital cannot be raised on attractive terms[121]. Costs and Strategic Considerations - Costs associated with drug discovery, preclinical development, and clinical trials for product candidates are significant and ongoing[120]. - Regulatory review costs and the expenses related to marketing approvals for successful clinical trials are critical factors for future product launches[120]. - The costs of maintaining and enforcing intellectual property rights are a significant consideration for the company[120]. - The company is focused on the costs of future activities related to product sales, medical affairs, and distribution for approved product candidates[120]. - The company is evaluating third-party manufacturers and suppliers, which adds to the overall manufacturing process development costs[120]. - Ongoing collaborations and the ability to establish new partnerships on favorable terms are essential for the company's growth strategy[120]. - The terms of current and future license agreements and collaborations will impact the company's strategic direction[120].

Financial Performance - For the three months ended March 31, 2025, Connect Biopharma reported a net loss of $10.3 million, or $0.19 per share, compared to a net loss of $8.7 million, or $0.16 per share, for the same period in 2024[7]. - Total operating expenses for the three months ended March 31, 2025, were $11.4 million, compared to $12.6 million for the same period in 2024[14]. Cash and Investments - Cash, cash equivalents, and short-term investments were $84.0 million as of March 31, 2025, expected to fund operations into 2027[7]. - Total assets as of March 31, 2025, were $92.7 million, down from $101.3 million as of December 31, 2024[16]. Research and Development - Research and Development expense decreased to $6.6 million for the three months ended March 31, 2025, from $8.7 million in the same period in 2024, a reduction of $2.1 million[7]. - Connect Biopharma initiated Phase 2 Seabreeze STAT studies for rademikibart as an adjunct treatment for acute exacerbations in asthma and COPD, with topline data expected in 1H 2026[5]. - Rademikibart demonstrated a mean difference from placebo in forced expiratory volume of +420 mL in patients with eosinophilic-driven asthma after 24 weeks, one of the largest increases reported for a biologic[7]. - The company completed a positive Type C meeting with the FDA, aligning on the Phase 2 Seabreeze study protocols[7]. - Four posters were accepted for presentation at the ATS 2025 International Conference, supporting the development of rademikibart for patients with moderate-to-severe asthma or COPD[7]. General and Administrative Expenses - General and Administrative expense increased to $4.8 million for the three months ended March 31, 2025, compared to $4.0 million for the same period in 2024, an increase of $0.8 million[7].