Connect Biopharma Holdings Ltd

Connect Biopharma, a clinical-stage biopharmaceutical company headquartered in San Diego, California, is focused on transforming care for asthma and chronic obstructive pulmonary disease (COPD) ¹. The company is advancing rademikibart, a next-generation antibody targeting interleukin-4-receptor alpha (IL-4Rα) ². Asthma is a chronic inflammatory disease affecting an estimated 23 million adults and 5 million children in the U.S., and 262 million people globally in 2019, causing 455,000 deaths ³. COPD, an irreversible inflammatory lung disease, affects approximately 14.2 million adults in the U.S. and an estimated 480 million people globally, leading to 3.5 million deaths annually ⁴. Both diseases are associated with severe exacerbations requiring emergency department visits and hospitalizations, with approximately one million asthma patients and 1.3 million COPD patients visiting emergency departments annually in the U.S. for acute exacerbations ⁵. A significant unmet need exists for more effective acute treatment, as approximately 50% of both asthma and COPD patients fail to improve on first-line treatments and meet treatment failure criteria within four weeks of an exacerbation ⁶.

Rademikibart is a human monoclonal IgG4 antibody directed against IL-4Rα, inhibiting both IL-4 and IL-13 signaling ⁷. The company believes rademikibart's high binding affinity and potency for IL-4Rα may lead to an improved clinical response and a differentiating safety profile ⁸. Connect Biopharma is focused on advancing rademikibart for eosinophilic-driven respiratory diseases, specifically acute exacerbations of asthma and COPD ⁹. In May 2025, two Phase 2 trials, Seabreeze STAT ASTHMA and Seabreeze STAT COPD, were initiated to evaluate rademikibart plus Standard of Care (SoC) compared to SoC plus placebo in patients experiencing acute exacerbations ¹⁰. The primary endpoint for these trials is treatment failure over 28 days after randomization ¹¹.

Connect Biopharma's core business model revolves around the development and potential commercialization of novel biopharmaceutical product candidates, primarily rademikibart, for inflammatory diseases. The company generates revenue through upfront payments, milestone achievements, and cost reimbursements from collaboration agreements, such as the exclusive License and Collaboration Agreement with Simcere Pharmaceutical Co., Ltd. (Simcere) for rademikibart in Greater China ¹². Future revenue is expected from royalties on net sales if products are approved and commercialized ¹³. The primary customer segments, if approved, would be physicians and patients suffering from asthma and COPD.

Rademikibart is the company's only product candidate currently in clinical development ¹⁴. It is being advanced for the treatment of acute exacerbations of asthma and COPD, with two Phase 2 trials initiated in May 2025 ¹⁵. The company also highlights rademikibart's potential for chronic utilization in asthma and COPD, supported by previous Phase 2b global chronic asthma study results ¹⁶. In 2023, Connect Biopharma entered into an exclusive License and Collaboration Agreement with Simcere Pharmaceutical Co., Ltd. to develop and commercialize rademikibart in Greater China for all indications ¹⁷. As of December 31, 2025, Connect Biopharma had received an upfront payment of $21 million ¹⁸ and $6.5 million ¹⁹ for development milestones and cost reimbursements under this agreement ²⁰. Simcere submitted a New Drug Application for rademikibart to the NMPA of China for the treatment of Atopic Dermatitis (AD) in adults and adolescents in July 2025 ²¹. Connect Biopharma is eligible to receive remaining milestone payments up to an aggregate amount of approximately $110 million ²² and tiered royalties up to low double-digit percentages on net sales in Greater China ²³.

For the fiscal year ended December 31, 2025, Connect Biopharma reported net losses of $55.5 million ²⁴. As of December 31, 2025, the company had an accumulated loss of $400.8 million ²⁵. The company's financial statements indicate that substantially all losses have resulted from expenses incurred in research and development programs and general and administrative costs ²⁶.

Comparing year-over-year, the net loss increased from $15.6 million ²⁷ for the year ended December 31, 2024, to $55.5 million ²⁸ for the year ended December 31, 2025. This indicates a significant increase in operating losses.

Significant operational developments during the period include the initiation of two Phase 2 trials for rademikibart in acute asthma and COPD in May 2025 ²⁹. In April 2025, the company announced FDA alignment on the design of these Phase 2 trials ³⁰. New in vitro and preclinical mechanism of action data supporting rademikibart's potentially differentiated efficacy and safety profile were announced in January 2026 ³¹. In March 2026, positive topline data from a Phase 1 clinical pharmacology study of IV rademikibart in stable asthma or COPD patients demonstrated rapid improvement in FEV1 ³². The publication of positive data from the global Phase 2 trial of rademikibart in moderate-to-severe uncontrolled asthma in the American Journal of Respiratory and Critical Care Medicine was announced in March 2025 ³³. During the second and third quarters of 2025, clinical and preclinical data supporting rademikibart's development were presented at various international conferences ³⁴. In September 2025, results from a one-year AD study with rademikibart were published in the British Journal of Dermatology, showing equivalent efficacy for every 4-week administration compared to every 2-week administration during the maintenance period ³⁵. In March 2026, Simcere announced positive topline data from its Phase 3 study of rademikibart in moderate-to-severe AD ³⁶.

Connect Biopharma expects to report topline data for its ongoing Phase 2 acute exacerbation studies in mid-2026 ³⁷. The company's current development plan for rademikibart is supported by results from the completed global asthma trial CBP-201-WW002, which demonstrated greater FEV1 response in cross-study comparisons than currently approved biologics and rapid onset of action within 24 hours of subcutaneous dose ³⁸.

A major growth vector for Connect Biopharma is the advancement of rademikibart for the treatment of acute exacerbations of asthma and COPD ³⁹. The company initiated two Phase 2 trials, Seabreeze STAT ASTHMA and Seabreeze STAT COPD, in May 2025, with FDA alignment on their design ⁴⁰. This treatment setting represents a significant unmet medical need, as available standard of care therapy in the acute setting shows insufficient long-term treatment effect, with frequent exacerbations leading to re-visits to acute care settings ⁴¹. The company believes rademikibart, if approved, would offer significant healthcare cost savings by potentially reducing hospital length of stay and emergency department re-visits and rehospitalizations ⁴². The acute indications alone represent an untapped opportunity targeting approximately one million asthma and 1.3 million COPD patients in the U.S. annually who visit an emergency department for acute exacerbations ⁴³.

Another growth area is the potential for significant chronic utilization of rademikibart in asthma and COPD, building on its initial focus on acute indications ⁴⁴. The completed Phase 2 asthma clinical trial demonstrated encouraging long-term (6 month) efficacy and safety data, as well as rapid onset of action in less than 24 hours, supporting the ability to treat from acute to chronic administration ⁴⁵. This is crucial given that approximately 50% of both asthma and COPD patients treated with SoC meet criteria for treatment failure within four weeks of an exacerbation ⁴⁶. The company also plans to explore the potential for less frequent dosing than dupilumab ⁴⁷.

Operationally, the company's clinical development program is focused on achieving faster onset of action and greater clinical response for rademikibart, with a potentially favorable safety profile ⁴⁸. The company has undertaken a study to determine differences in the atomic-resolution 3D structures of rademikibart and dupilumab, providing a molecular and structural rationale for enhanced IL-4Rα inhibition by rademikibart and potentially insight into a different safety profile ⁴⁹.

Connect Biopharma expects its expenses to increase substantially as it conducts ongoing and planned preclinical studies and clinical trials, continues research and development activities, increases production capacity, and seeks regulatory approvals for its product candidates ⁵⁰. The company also anticipates additional costs for hiring personnel, protecting intellectual property, and potential commercialization or pipeline expansion ⁵¹. The development of biopharmaceutical product candidates is capital-intensive, and the company's existing capital will not be sufficient to fund rademikibart through regulatory approvals, necessitating additional capital for development and commercialization ⁵².

The company expects to incur significant costs associated with operating as a public company ⁵³. Future financing requirements will depend on factors such as the type, number, scope, progress, expansions, results, costs, and timing of clinical trials and preclinical studies, potential future safety concerns, manufacturing costs, regulatory review costs, intellectual property costs, and commercialization expenses ⁵⁴.

Connect Biopharma faces several material risks, including significant operating losses since inception and the expectation of continued losses for the foreseeable future, with an accumulated loss of $400.8 million as of December 31, 2025 ⁵⁵. The company will require substantial additional financing to achieve its goals, as existing capital is insufficient to fund rademikibart through regulatory approval ⁵⁶. Clinical drug development is a lengthy, expensive, and uncertain process, with potential for unforeseen costs or delays ⁵⁷. There is a dependence on patient enrollment in clinical trials, and delays or difficulties in enrollment could materially adversely affect research and development efforts ⁵⁸. Product candidates may be associated with serious adverse events or undesirable side effects, which could delay or halt clinical development or regulatory approval ⁵⁹. The company's approach to T cell modulation activity is unproven, and there is no guarantee of developing commercially valuable products ⁶⁰. As a company, Connect Biopharma has no experience submitting NDAs or BLAs ⁶¹. Disruptions at regulatory agencies due to shifting governmental policies or funding shortages could hinder timely approval ⁶². Product candidates approved as biologics may face earlier competition than anticipated due to biosimilar pathways ⁶³. The company relies on third parties for preclinical studies, clinical trials, and manufacturing, increasing risks of insufficient supplies or delays ⁶⁴. Commercial success depends on market acceptance and adequate reimbursement levels, which are uncertain ⁶⁵. The increasing use of AI and machine learning in drug discovery introduces new and evolving risks related to functionality, data quality, competition, intellectual property, cybersecurity, and regulatory compliance ⁶⁶. The company is dependent on key management and scientific personnel, and their loss or inability to recruit additional personnel could harm the business ⁶⁷. Significant changes in U.S. laws or policies, including trade policies and tariffs, may adversely affect the business ⁶⁸. The ability to obtain, maintain, protect, and enforce intellectual property is crucial, and any failure could harm the competitive position ⁶⁹. The trading price of ordinary shares could be highly volatile, and unstable market and economic conditions may have serious adverse consequences ⁷⁰. As a foreign private issuer, the company is not subject to certain U.S. securities law disclosure requirements, which may limit publicly available information ⁷¹. Changes in PRC political and economic policies, government intervention, and compliance with PRC data security and privacy laws may materially and adversely affect operations and the value of ordinary shares ⁷².

Management's message to shareholders emphasizes the company's dedication to transforming care for asthma and COPD through the advancement of rademikibart, a next-generation antibody targeting IL-4Rα ⁷³. They highlight the significant unmet need and market opportunity in both acute asthma and COPD, noting that approximately one million asthma and 1.3 million COPD patients in the U.S. annually visit emergency departments for acute exacerbations ⁷⁴. Management expects to report topline data for the ongoing Phase 2 acute exacerbation studies in mid-2026 ⁷⁵. They also point to the potential for rademikibart to offer significant healthcare cost savings by reducing hospital stays and re-visits ⁷⁶. A key strategic priority is to leverage rademikibart's potential for faster onset of action and greater clinical response, with a potentially favorable safety profile, and to explore less frequent dosing than dupilumab ⁷⁷. The company also emphasizes the potential for significant chronic utilization in asthma and COPD, building on the initial focus on acute indications ⁷⁸.