Product Sales and Market Position - ETUARY® (pirfenidone) generated annual sales of $106.1 million in 2025, maintaining a leading market position in the treatment of pulmonary fibrosis [32]. - Etorel® (nintedanib) was launched in June 2025 and generated $4.6 million in sales in 2025, expanding treatment options for patients with pulmonary fibrosis [34]. - Contiva® (avatrombopag) was launched in March 2025 and generated $5.5 million in sales in 2025, targeting thrombocytopenia associated with chronic liver disease [37]. - Sales of ETUARY® reached $106.1 million in 2025, although its market share has declined due to increased competition [65]. - Gyre Pharmaceuticals has achieved sustained profitability due to increased market demand for ETUARY®, facing limited competition in the IPF drug market [203]. Clinical Trials and Drug Development - In a Phase 3 trial, Hydronidone achieved a primary endpoint with 52.85% of treated patients showing ≥1-stage fibrosis regression at Week 52, compared to 29.84% in the placebo group (p=0.0002) [46]. - Hydronidone is expected to submit a New Drug Application (NDA) for conditional approval in the first half of 2026, following positive Phase 3 trial results [47]. - A Phase 1 clinical trial of Hydronidone for MASH-Associated Liver Fibrosis was completed, showing no serious adverse events and a mean elimination half-life of approximately five to six hours [90][93]. - The planned Phase 2 clinical trial for Hydronidone is expected to be filed in 2026, aiming to obtain preliminary proof-of-concept data [94][95]. - A Phase 3 trial of pirfenidone for the treatment of PD completed enrollment in 2025 with a total of 272 patients across 18 clinical research centers in China [99]. - The Phase 2 clinical trial of F573 initiated in March 2023 aims to evaluate efficacy and safety in patients with liver injury, with a total of 16 patients enrolled in the first stage [102]. - The Phase 1 clinical trial of F230 was approved in May 2024, with the first subject enrolled in May 2025, consisting of single and multiple ascending dose studies [104]. Market Trends and Prevalence - The prevalence of Idiopathic Pulmonary Fibrosis (IPF) in China increased from 89,144 patients in 2018 to 161,000 patients in 2024, with a CAGR of 10.24% [63]. - The total market size of IPF in China grew from $23.9 million in 2018 to $196.1 million in 2024, reflecting a CAGR of 42% [63]. - The prevalence of Chronic Obstructive Pulmonary Disease (COPD) is a significant global health burden, with a need for treatments that may slow long-term disease progression [60]. - The prevalence of Chronic Hepatitis B (CHB)-associated liver fibrosis globally increased from 228.9 million patients in 2018 to 272.2 million patients in 2024 [73]. - The prevalence of Acute Liver Failure (ALF) in China was 42,440 patients in 2018 and is expected to decline to 29,020 patients by 2032, with a market size projected to decrease from $274.2 million in 2018 to $191.1 million by 2032 [83]. - The prevalence of PAH in China increased from 50,600 patients in 2018 to 61,700 patients in 2024, projected to reach 71,300 patients by 2032 [86]. - The prevalence of COPD in China rose from 103.5 million patients in 2018 to 108.4 million patients in 2024, projected to reach 118.7 million patients by 2032 [89]. Regulatory and Compliance - The FDA's review process for an NDA typically aims to be completed within ten months for standard applications and six months for priority reviews [137]. - The company must submit an IND to the FDA before beginning any clinical trials, which becomes effective 30 days after submission unless safety concerns arise [128]. - The FDA may issue an approval letter or a Complete Response letter after evaluating an NDA, detailing any deficiencies identified [138]. - The FDA may grant orphan drug designation to products intended to treat rare diseases affecting fewer than 200,000 individuals in the U.S. [146]. - Orphan drug exclusivity grants a product seven years of exclusive approval after the first FDA approval for the designated disease, preventing other applications for the same indication [147]. - The FDA requires compliance with regulatory standards post-approval, including record-keeping and reporting of adverse experiences [152]. - The FDA enforces strict regulations on marketing and promotion, allowing only claims approved in the product's labeling [155]. Company Operations and Structure - The company completed a business combination to acquire an indirect controlling interest in Gyre Pharmaceuticals on October 30, 2023 [123]. - As of December 31, 2025, the company has seven full-time employees in the United States [121]. - The company is headquartered in San Diego, California, and commenced operations in 2002 [123]. - As of December 31, 2025, Gyre Pharmaceuticals had 618 total employees, with a significant portion in sales and marketing roles [206]. - The company has a dedicated in-house R&D team of 66 employees in the PRC, focusing on drug discovery, chemistry, manufacturing and control, clinical development, medical affairs, and regulatory affairs [215]. Intellectual Property and Patents - Gyre owns 18 granted patents globally and has multiple pending patent applications that are material to its business, with a focus on protecting its core technology and intellectual property [109]. - Patent owners can apply for a patent extension of up to five years post-NDA approval, with a maximum total patent term of 14 years [164]. Financial and Market Challenges - Coverage and reimbursement from third-party payors are critical for product acceptance, with significant uncertainty regarding reimbursement levels for approved products [182][184]. - Third-party payors increasingly challenge medical product pricing and assess medical necessity, which can affect product sales and physician utilization [184]. - The Inflation Reduction Act of 2022 allows CMS to negotiate prices for high-spend drugs, with the first ten drugs announced for negotiation on August 29, 2023 [187]. - The IRA introduces an "inflation rebate" for Medicare patients, requiring drug manufacturers to pay rebates if prices increase faster than inflation, effective from 2023 [187]. Compliance and Legal Risks - The company may face legal risks and compliance costs due to evolving privacy laws and regulations regarding artificial intelligence and machine learning [180][181]. - Compliance with data privacy laws, such as HIPAA and state-specific regulations, is essential to avoid penalties and protect personal information [175][179]. - The company has formed a labor union to represent employees and has maintained good working relationships without material claims or disputes in 2025 [209].

Revenue Performance - Full-year 2025 revenue increased 10% year-over-year to $116.6 million, within revised guidance range[1] - Full year 2026 revenue guidance is set at $100.5 to $111.0 million, representing a decline of approximately 13.8% to 4.8% compared to 2025[15] - Sales of ETUARY® reached $106.1 million for the full year 2025, compared to $105.0 million in 2024[5] - Gyre Therapeutics reported revenues of $37.2 million for Q4 2025, a 33.5% increase from $27.9 million in Q4 2024[30] - The company achieved net sales of $105.8 million for the full year 2024, representing a 1.0% increase from $105.8 million in 2023[30] Expenses and Financials - Selling and marketing expenses for the full year 2025 were $65.2 million, an increase of $7.7 million from 2024[14] - Research and development expenses for the full year 2025 totaled $13.7 million, up from $12.0 million in 2024[14] - The total operating expenses for Q4 2025 were $37.1 million, up from $27.2 million in Q4 2024, reflecting a 36.4% increase[30] - The company reported a net loss of $1,366 million for the three months ended December 31, 2025, compared to a net income of $569 million for the same period in 2024[34] - For the full year 2025, the company reported a net loss of $9,880 million, compared to a net income of $17,898 million in 2024[34] - The total stock-based compensation for the full year 2025 was $7,157 million, compared to $831 million in 2024[34] - The provision for income taxes for the three months ended December 31, 2025, was $1,300 million, compared to $203 million in the same period of 2024[34] - The provision for income taxes for the full year 2025 was $4,556 million, down from $5,320 million in 2024[34] Clinical Trials and Product Development - The company completed patient enrollment in the 52-week Phase 3 pirfenidone trial with 272 patients across 18 sites[4] - The company plans to submit a New Drug Application (NDA) for Hydronidone in the first half of 2026, following alignment with China's CDE[2] - Hydronidone has completed Phase 3 clinical evaluation in China for chronic hepatitis B-associated liver fibrosis[21] - The company plans to submit a U.S. IND application for Hydronidone and conduct a hepatic impairment study in U.S. subjects[26] Acquisitions and Investments - Gyre announced an agreement to acquire Cullgen for approximately $300 million, expected to close in Q2 2026[7] - The company has a 69.7% equity interest in Gyre Pharmaceuticals, which is developing Hydronidone for liver fibrosis[23] Cash and Assets - Gyre's cash and cash equivalents increased to $37.1 million as of December 31, 2025, compared to $11.8 million at the end of 2024[31] - Gyre's total assets increased to $166.1 million as of December 31, 2025, up from $125.4 million in 2024[31] Net Income and Adjustments - Net income for the full year 2025 was $9.9 million, down from $17.9 million in 2024[17] - Non-GAAP adjusted net income for the full year 2025 was $18.9 million, compared to $16.9 million in 2024[17] - Non-GAAP adjusted net income for the three months ended December 31, 2025, was $4,268 million, up from $1,145 million in the prior year[34] - Non-GAAP adjusted net income for the full year 2025 was $18,886 million, an increase from $16,882 million in 2024[34] Stock-Based Compensation and Fair Value Adjustments - Stock-based compensation increased significantly to $4,597 million in Q4 2025 from $567 million in Q4 2024[34] - The company continues to adjust its financials based on the fair value of warrants using the Black-Scholes option pricing model[34] - The gain from the change in fair value of warrants was a loss of $263 million for Q4 2025, compared to a loss of $194 million in Q4 2024[34]

Core Insights - Crescent Biopharma, Inc. (CBIO) is experiencing significant challenges in capital efficiency, with a Return on Invested Capital (ROIC) of -74.58% compared to a Weighted Average Cost of Capital (WACC) of 9.98% [2][6] - In contrast, Pieris Pharmaceuticals (PIRS) demonstrates strong capital efficiency with a ROIC of 22.28% against a WACC of 7.52%, making it the most efficient among its peers [3][6] - Other competitors like CytomX Therapeutics (CTMX) show a positive ROIC of 18.76% with a WACC of 15.09%, indicating returns above their cost of capital, though less efficiently than PIRS [4][6] - Galmed Pharmaceuticals, Cidara Therapeutics, and MacroGenics exhibit negative ROICs, indicating capital efficiency challenges similar to CBIO, but with less severe inefficiencies [5][6] Capital Efficiency Comparison - CBIO's ROIC to WACC ratio is -7.47, highlighting significant inefficiency in capital utilization [2] - PIRS has a ROIC to WACC ratio of 2.96, indicating effective returns on invested capital [3] - CTMX's ROIC to WACC ratio is 1.24, suggesting it generates returns above its cost of capital, but not as efficiently as PIRS [4] - Other peers have less negative ROIC to WACC ratios than CBIO, suggesting relatively better capital utilization despite still being inefficient [5]

Core Insights - Crescent Biopharma has established a partnership with Kelun-Biotech to expand its oncology pipeline and accelerate its combination strategy with CR-001, a PD-1 x VEGF bispecific antibody, and multiple antibody-drug conjugates (ADCs) [1][5] - The ASCEND Phase 1/2 global clinical trial for CR-001 is currently underway, with three additional clinical trials expected to initiate in 2026 [1][2] - The company completed a $185 million private placement, which will support key clinical data readouts starting in Q1 2027 and provide a cash runway into 2028 [1][9] Business Highlights - The partnership with Kelun-Biotech allows Crescent to leverage exclusive rights for CR-001 in Greater China while obtaining rights for CR-003 in the U.S. and Europe [5] - Crescent's CEO highlighted the transformative nature of 2025 for the company, emphasizing the advancement of next-generation therapies and the ongoing ASCEND trial for CR-001 [2] - The company anticipates proof-of-concept clinical data from the ASCEND trial in Q1 2027, including initial safety and preliminary antitumor activity [5][6] Financial Performance - As of December 31, 2025, Crescent reported cash and cash equivalents of $213.2 million, expected to fund operations into 2028 [9] - The company generated revenue of $10.8 million for the year ended December 31, 2025, attributed to a $20 million upfront payment from Kelun-Biotech [9] - Research and development expenses increased significantly to $138.1 million for the year, driven by the development of CR-001 and CR-002, along with an $80 million upfront payment to Kelun-Biotech for CR-003 [10] Pipeline Developments - CR-001 is positioned as a potential immuno-oncology backbone for treating solid tumors, with ongoing trials evaluating its efficacy in various cancer types [2][5] - Crescent plans to initiate a Phase 1/2 trial for CR-002 in mid-2026, with proof-of-concept data expected in the second half of 2027 [14] - CR-003 has received IND approval in China, with a Phase 1/2 trial expected to start in Q1 2026 [14]

Core Viewpoint - Crescent Biopharma is focused on advancing innovative cancer therapies and will present at key investor conferences in March 2026 [1][3]. Company Overview - Crescent Biopharma aims to become a leading oncology company by developing next-generation therapies for cancer patients [2]. - The company's clinical-stage pipeline includes a PD-1 x VEGF bispecific antibody and novel antibody-drug conjugates (ADCs) [2]. - Crescent intends to leverage multiple modalities and established targets to develop transformative therapies for various solid tumors [2]. Upcoming Events - Crescent Biopharma will participate in the TD Cowen 46th Annual Health Care Conference on March 2, 2026, at 3:50 p.m. ET in Boston [3]. - The company will also be featured in the Leerink Partners 2026 Global Healthcare Conference on March 11, 2026, at 8:40 a.m. ET in Miami [3].

Core Insights - Crescent Biopharma has initiated the ASCEND Phase 1/2 clinical trial for CR-001, a PD-1 x VEGF bispecific antibody targeting advanced solid tumors, with the first patient dosed [1][2] - The trial aims to evaluate CR-001's safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity across multiple solid tumor types, including NSCLC and gastrointestinal and gynecological cancers [2][3] - Crescent anticipates reporting proof-of-concept data from the ASCEND trial in Q1 2027, which will include initial safety and efficacy results [3] Company Overview - Crescent Biopharma is a clinical-stage biotechnology company focused on developing innovative therapies for cancer patients, with a pipeline that includes CR-001 and novel antibody-drug conjugates (ADCs) [6] - The company aims to establish itself as a leading oncology firm by advancing transformative therapies for solid tumors through various treatment modalities [6] Product Details - CR-001 (also known as SKB118) is designed to block PD-1 and VEGF, potentially enhancing T cell activity against tumors while reducing blood supply to cancer cells [4] - Preclinical studies have shown that CR-001 exhibits cooperative pharmacology and robust antitumor activity, with plans for combination trials with ADCs expected to start in the second half of 2026 [4] Strategic Collaborations - Crescent has granted Sichuan Kelun-Biotech exclusive rights to research, develop, and commercialize CR-001 in Greater China, which includes mainland China, Hong Kong, Macau, and Taiwan [5]

Core Viewpoint - Crescent Biopharma, a clinical-stage biotechnology company, is focused on advancing innovative therapies for cancer patients and will participate in a fireside chat at the Guggenheim Emerging Outlook: Biotech Summit 2026 [1] Company Overview - Crescent Biopharma aims to become a leading oncology company by developing the next generation of cancer therapies [3] - The company's clinical-stage pipeline includes a PD-1 x VEGF bispecific antibody and novel antibody-drug conjugates (ADCs) [3] - Crescent intends to leverage multiple modalities and established targets to advance transformative therapies for solid tumors, either as single agents or in combination regimens [3] Event Participation - Management is scheduled to participate in a fireside chat on February 12, 2026, at 11:30 a.m. ET [1] - A live webcast of the presentation will be available on the company's website, with a replay accessible for 90 days post-event [2]

As filed with the U.S. Securities and Exchange Commission on January 7, 2026. THE SECURITIES ACT OF 1933 Crescent Biopharma, Inc. (Exact name of registrant as specified in its charter) Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code Number) Cayman Islands 2834 06-1686563 (I.R.S. Employer Identification No.) 300 Fif ...

Core Insights - Crescent Biopharma has received regulatory clearances for its investigational new drugs CR-001 and CR-003, with plans to initiate multiple clinical trials in 2026 [1][2][3] Group 1: Regulatory Approvals - The U.S. FDA has cleared Crescent's IND for CR-001, a PD-1 x VEGF bispecific antibody [2] - Crescent's partner, Kelun-Biotech, has received IND approval for CR-003 (SKB105) from the NMPA of China [2] Group 2: Clinical Trials - The Phase 1/2 ASCEND global clinical trial for CR-001 is set to begin in the first quarter of 2026, targeting treatment-naïve and previously treated patients with various solid tumors [3] - The ASCEND trial aims to enroll up to 290 participants to assess the clinical profile of CR-001, with proof-of-concept data expected in the first quarter of 2027 [3] Group 3: Product Details - CR-001 (SKB118) is designed to block PD-1 and VEGF, aiming to enhance T cell activity against tumors and reduce blood supply to tumors [5] - CR-003 (SKB105) is an ADC targeting integrin beta-6 (ITGB6) with a topoisomerase 1 inhibitor payload, designed to minimize systemic toxicity [7] Group 4: Strategic Collaboration - Crescent has a strategic collaboration with Kelun-Biotech, granting Crescent exclusive rights to develop and commercialize CR-003 outside Greater China, while Kelun-Biotech has rights for CR-001 in Greater China [4]

SEIZE THE MOMENT for a brighter future CRESCENT BIOPHARMA STRATEGIC PARTNERSHIP & PIPELINE UPDATE DECEMBER 4, 2025 NASDAQ: CBIO Disclaimers 2 Program Forward-Looking Statements Certain statements in this presentation, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the "safe harbor" provisions under the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, ...