CRESCENT BIOPHARMA, INC.

Crescent Biopharma, Inc. is a clinical-stage biotechnology company focused on delivering transformative therapies for people living with cancer, operating within the highly competitive oncology and biopharmaceutical industry. The company is executing across two distinct strategies: developing CR-001, a PD-1 x VEGF bispecific antibody designed to replace pembrolizumab as the foundational immuno-oncology backbone, and building a portfolio of potentially best-in-class antibody drug conjugates (ADCs). The filing notes that worldwide annual sales of immune checkpoint inhibitors are estimated to be in excess of $50 billion ¹, over half of which are driven by sales of Keytruda, and that the ADC market had 2025 sales of close to $13 billion ² with a projected market of over $41 billion by 2035 ³. The company is subject to risks common to early-stage biotechnology companies, including the need for substantial additional capital to fund operations.

The company faces significant competition from major pharmaceutical and biotechnology companies. Competitors named in the filing for CR-001 include Merck (Keytruda), Bristol Myers Squibb (Opdivo), Genentech (Tecentriq), AstraZeneca (Imfinzi), Summit Therapeutics Inc. (ivonescimab), BioNTech SE, LaNova Medicines Ltd., and Compass Therapeutics, Inc. For ADC development, competitors include Pfizer (PDL1V, sigvotatug vedotin) and Henlius (HLX-43). The company's competitive advantages are stated to be its proprietary molecule CR-001, which incorporates the targeting, binding, cooperativity and pharmacokinetics of ivonescimab, and its strategy to combine CR-001 with ADC therapies. The filing states that the company believes CR-001 has the potential to deliver improved clinical efficacy and safety over Keytruda, the best-selling drug in the world.

The company generates revenue through licensing agreements, specifically the Kelun CR-001 License Agreement, and has not generated any revenue from product sales. The core business model involves the research and development of oncology product candidates, with a focus on advancing its pipeline through preclinical studies and clinical trials. The company relies on third-party agreements, including those with Paragon Therapeutics, Inc. and Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., for research, development, and manufacturing activities. The company's primary customer segments are not explicitly defined in the filing, but its strategy involves seeking regulatory approvals and commercializing products in the United States and other key markets.

The company's pipeline includes three main product candidates. CR-001 is a PD-1 x VEGF bispecific antibody designed to incorporate the functional properties of ivonescimab. The company initiated a global Phase 1/2 trial (ASCEND trial) in the first quarter of 2026, enrolling patients with up to eight types of solid tumors, and expects to enroll up to 290 patients ⁴. CR-002 is a PD-L1-directed ADC with a topoisomerase payload, designed to deliver a topoisomerase toxin to cancer cells that express PD-L1. The company plans to submit an IND for CR-002 in mid-2026 and initiate a Phase 1/2 trial in the second half of 2026. CR-003 (also known as SKB105) is an ITGB6-directed ADC licensed from Kelun, for which a Phase 1/2 trial is anticipated to be initiated in the first quarter of 2026 in China.

The company's product candidates are designed to address a broad range of solid tumors. CR-001 is being developed for multiple solid tumor indications, with an initial focus on thoracic, gastrointestinal, and gynecologic cancers. The company believes there are over 40 indications where CR-001 could be first-in-class outside of China. CR-002 is designed for the treatment of PD-L1 expressing tumors, which the filing states are overexpressed by over 35 percent of certain types of cancer ⁵. CR-003 targets ITGB6, which is overexpressed in numerous solid tumors including lung, head and neck, pancreatic, breast, and cervical cancers. The company intends to combine CR-001 and ADC therapies to create synergistic combinations.

Significant operational developments during the period include the consummation of a reverse recapitalization merger with GlycoMimetics, Inc. on June 13, 2025, after which the company changed its name to Crescent Biopharma, Inc. and redomesticated to the Cayman Islands on June 16, 2025. The company entered into a License and Collaboration Agreement with Kelun on December 2, 2025, paying an upfront payment of $80 million ⁶ for exclusive rights to SKB105 (CR-003) outside of Greater China. Concurrently, the company granted Kelun an exclusive license for CR-001 in Greater China, receiving an upfront payment of $20 million ⁷ in January 2026. The company also completed a private placement on December 8, 2025, raising approximately $185.0 million ⁸ in gross proceeds. On February 24, 2026, the company provided notice to terminate the ADC Paragon Option Agreement, effective March 26, 2026.

The company reported a net loss of $153.9 million ⁹ for the twelve months ended December 31, 2025, compared to a net loss of $17.9 million ¹⁰ for the period from September 19, 2024 (inception) through December 31, 2024. Total operating expenses were $163.5 million ¹¹ for the twelve months ended December 31, 2025, driven by research and development expenses of $138.1 million ¹² and general and administrative expenses of $25.4 million ¹³. The company generated license revenue of $10.8 million ¹⁴ for the twelve months ended December 31, 2025. As of December 31, 2025, the company had cash and cash equivalents of $213.2 million ¹⁵ and an accumulated deficit of $171.8 million ¹⁶.

A primary growth vector is the clinical development of CR-001, which the company believes has the potential to replace pembrolizumab as the foundational immuno-oncology backbone. The company initiated a global Phase 1/2 trial (ASCEND trial) in the first quarter of 2026, enrolling patients with up to eight solid tumor types, and anticipates reporting proof-of-concept clinical data in the first quarter of 2027, including initial safety, pharmacokinetic, pharmacodynamic, and early anti-tumor activity. The company believes that because CR-001 incorporates the functional properties of ivonescimab, early clinical data from ivonescimab can serve as important validation, potentially accelerating timelines and reducing the number of patients in late-stage trials. The partnership with Kelun is designed to enable parallel generation of clinical data for CR-001 in both Chinese and non-Chinese patient populations.

Another major growth vector is the advancement of the company's ADC programs, CR-002 and CR-003, and their combination with CR-001. The company anticipates initiating monotherapy clinical trials with CR-002 in the second half of 2026 and with CR-003 in the first quarter of 2026. The company also anticipates initiating the first CR-001 ADC combination trial in the second half of 2026. The company plans to continue to expand its product portfolio through a combination of internal development, its relationship with Paragon, and external sources. The company believes that the potential to combine CR-001 with ADCs is a key element of its partnership with Kelun, which is designed to provide a competitive advantage by accelerating clinical evaluation of CR-001 in combination with a broad portfolio of ADCs.

The filing does not provide specific quantitative margin or cost outlook, efficiency targets, or restructuring targets. The company expects research and development expenses to continue to increase in connection with its ongoing activities, particularly as it advances product candidates through preclinical studies and clinical trials. General and administrative expenses are also expected to increase substantially as the company increases headcount and incurs costs associated with being a public company.

The company does not currently own or operate manufacturing facilities and relies on third-party contract manufacturing organizations (CMOs). The company has contracted with WuXi Biologics and Charles River Laboratories for manufacturing and development activities. The company employs personnel with technical, manufacturing, analytical, and quality experience to oversee these relationships. The company's headquarters is located in Waltham, Massachusetts, where it leases approximately 25,000 square feet of office space ¹⁷ under a sublease that expires in February 2029 ¹⁸.

The company's capital allocation strategy is focused on funding its research and development programs. The company expects to finance its cash needs through a combination of equity offerings, debt financings, and license and development agreements. The company does not anticipate paying any cash dividends in the foreseeable future. The filing does not provide specific figures for planned R&D spending, capital expenditure plans, or share repurchase authorizations beyond the transactions already completed.

The company faces significant headwinds and constraints, including the need to raise substantial additional capital to fund operations. The company has a limited operating history, has not completed any clinical trials, and has no products approved for commercial sale. The company is substantially dependent on the success of its lead program, CR-001, and its ADC programs, CR-002 and CR-003. The company faces intense competition from entities with greater financial resources and expertise. The regulatory approval process is lengthy, time-consuming, and inherently unpredictable. The company also faces risks related to its reliance on third parties for manufacturing and clinical trials, as well as risks related to intellectual property protection.

The company has identified several execution risks that could impact its growth plan. These include potential delays in clinical trials due to patient enrollment difficulties, the possibility that preclinical or clinical results may not be predictive of future results, and the risk that product candidates may be associated with adverse side effects. The company also faces risks related to its reliance on foreign CROs and CMOs, particularly those operating in China, which could be affected by geopolitical tensions, tariffs, or legislation such as the BIOSECURE Act. The company's estimates of market opportunity and forecasts of market growth may prove to be inaccurate.

The company is substantially dependent on the success of its lead program, CR-001, and its ADC programs, CR-002 and CR-003, and there is no assurance that clinical trials will be successful or that regulatory approval will be obtained. The company has never generated revenue from product sales and has incurred significant operating losses, reporting a net loss of $153.9 million ¹⁹ for the twelve months ended December 31, 2025, and an accumulated deficit of $171.8 million ²⁰ as of that date. The company will need to raise substantial additional capital to fund operations, and such funding may not be available on acceptable terms. The company faces intense competition from entities with significantly greater financial resources, including Merck, Bristol Myers Squibb, and Summit Therapeutics. The company does not currently own any issued patents and relies on in-licensed intellectual property from Paragon and Kelun, and its ability to obtain and protect patent rights is uncertain.

Management's message emphasizes a bold vision to build the next leading biotechnology oncology company by executing across two distinct strategies: developing CR-001 as a potential replacement for pembrolizumab and building a robust portfolio of ADCs. The key themes are the potential of CR-001 to build upon the transformative clinical efficacy observed with ivonescimab and the strategic importance of combining CR-001 with ADC therapies. Management's forward-looking statements include the anticipation of initiation of CR-002 and CR-003 monotherapy clinical trials in 2026 as well as the first ADC combination trial with CR-001. Management also anticipates reporting proof-of-concept clinical data from the ASCEND trial in the first quarter of 2027. The filing states that management expects that existing cash will be sufficient to fund operating plans for at least twelve months from the date of filing.