As filed with the Securities and Exchange Commission on December 11, 2025 Registration No. 333-291628 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 (Amendment No. 1) REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 SHUTTLE PHARMACEUTICALS HOLDINGS, INC. (Exact name of registrant as specified in its charter) David E. Danovitch, Esq. Aaron M. Schleicher, Esq. Sullivan & Worcester LLP 1251 Avenue of the Americas, 19 Floor New York, NY 10020 (212) 660-3060 From time to ...

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Rockville, Maryland--(Newsfile Corp. - November 21, 2025) - Shuttle Pharmaceuticals Holdings, Inc. (NASDAQ: SHPH) ("Shuttle" or the "Company") today announced that it has closed the acquisition of the assets and liabilities of 1542770 B.C. Ltd. d/b/a Molecule.ai ("Molecule"), a Canadian artificial intelligence company specializing in molecular discovery and drug development technologies.Under the terms of the agreement, 1563868 B.C. Ltd., a wholly owned subsidiary of Shuttle, acquired substantially all of ...

(Exact name of registrant as specified in its charter) FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 SHUTTLE PHARMACEUTICALS HOLDINGS, INC. As filed with the Securities and Exchange Commission on November 18, 2025 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 401 Professional Drive, Suite 260 Gaithersburg, MD 20879 (240) 430-4212 (Address, including zip code, and telephone number, including area code, of registrant's principal executive offi ...

Revenue and Loss - Total revenue for the three months ended September 30, 2025, was $0, unchanged from the same period in 2024[147] - Net loss for the three months ended September 30, 2025, was $2.3 million, a decrease of $1.4 million, or 38%, from a net loss of $3.8 million in 2024[147] - Net loss for the nine months ended September 30, 2025, was $9.1 million, an increase of $1.6 million, or 21%, from a net loss of $7.5 million in 2024[151] - The company incurred a net loss of $9.1 million with no revenues generated during the nine months ended September 30, 2025, and had working capital of approximately $1.3 million[158] Expenses - Research and development (R&D) expenses decreased by $0.5 million, or 33%, to $0.9 million for the three months ended September 30, 2025, compared to $1.4 million in 2024[147] - General and administrative expenses increased by $0.6 million, or 169%, to $0.9 million for the three months ended September 30, 2025, primarily due to investor relations advertising costs[148] - Legal and professional expenses decreased by $0.9 million, or 67%, to $0.4 million for the three months ended September 30, 2025, due to lower accounting expenses compared to 2024[149] - Total operating expenses decreased by $0.8 million, or 26%, to $2.3 million for the three months ended September 30, 2025[147] - R&D expenses for the nine months ended September 30, 2025, increased by $0.9 million, or 35%, to $3.5 million compared to $2.6 million in 2024[151] - General and administrative expenses for the nine months ended September 30, 2025, increased by $2.9 million, or 297%, to $3.8 million compared to $0.96 million in 2024[151] - Total operating expenses for the nine months ended September 30, 2025, increased by $3.2 million, or 54%, to $9.1 million compared to $5.9 million in 2024[151] - R&D compensation related expenses were $1.0 million for the nine months ended September 30, 2025, a 11% increase from $0.9 million in the same period of 2024, with a decrease in percentage of total R&D expenses from 36% to 29%[152] - General and Administrative expenses increased by $2.9 million, or 297%, from $1.0 million in the nine months ended September 30, 2024, to $3.8 million in the same period of 2025[153] - Legal and professional expenses decreased by $0.6 million, or 24%, during the nine months ended September 30, 2025, compared to the same period in 2024[154] - Cash used in operating activities was $8.5 million for the nine months ended September 30, 2025, an increase of 83% from $4.6 million in the same period of 2024[172] Assets and Capital - Total current assets increased by 48% to $3.3 million as of September 30, 2025, compared to $2.2 million as of December 31, 2024[170] - As of September 30, 2025, the company had cash and cash equivalents of $2.1 million, a 1237% increase from $156,656 as of September 30, 2024[172] - The company raised approximately $5.0 million in net proceeds from a public offering in March 2025 and $3.9 million from a private placement in June 2025[166][168] Financial Instruments and Valuation - The fair value of the October 2024 Convertible Bridge Notes is calculated based on mandatory conversion scenarios and the fair value per share at the balance sheet date[183] - The company uses Monte Carlo simulation models to estimate the fair value of financial instruments, which require subjective assumptions and can lead to significant variations in measurements[190] - Changes in the fair value of derivative financial instruments are recognized in the unaudited condensed consolidated statements of operations[191] - The company evaluates all warrants issued to determine their classification and fair value, with liability-classified warrants revalued at each reporting date[188] - The fair value of warrants is estimated at issuance and recorded to additional paid-in capital for equity-classified warrants[188] - The company does not provide quantitative and qualitative disclosures about market risk as it qualifies as a smaller reporting company[194] Other Considerations - The company is evaluating options regarding the potential termination of the Theradex Master Agreement, which could materially affect its clinical trials and financial position[157] - The company has no off-balance sheet arrangements that materially affect its financial condition or results of operations[178] - Research and development expenses are charged as incurred, including product development and personnel costs, with significant involvement from former executives[180]

Core Viewpoint - Shuttle Pharmaceuticals Holdings, Inc. has entered into a securities purchase agreement for approximately $2.5 million, which will be used for marketing, general corporate purposes, and working capital [1][2]. Group 1: Offering Details - The company will issue a pre-funded warrant to purchase up to 625,156 shares of common stock at an effective purchase price of $4.00 per share, priced above the market under Nasdaq rules [2]. - The offering is expected to close on or about November 4, 2025, subject to customary closing conditions [2][3]. Group 2: Placement Agent and Registration - WestPark Capital, Inc. is acting as the exclusive placement agent for the offering [3]. - The securities have not been registered under the Securities Act of 1933 and are offered only to accredited investors. The company has agreed to file registration statements with the SEC for the resale of shares [4]. Group 3: Company Overview - Shuttle Pharmaceuticals Holdings, Inc. is a clinical-stage pharmaceutical company focused on improving cancer therapy outcomes by developing novel drugs that sensitize cancer cells to radiation therapy [6]. - The company's mission is to advance precision medicine approaches to radiotherapy, enhancing treatment efficacy and patient quality of life [6].

Core Insights - Shuttle Pharmaceuticals is transitioning from a focus on radiation therapy to a broader mission of enhancing scientific intelligence through artificial intelligence [2][3] - The company has signed a Letter of Intent to acquire Molecule.ai for approximately $10 million, which will allow it to leverage AI for scientific reasoning and discovery [3][4] Company Update - The acquisition of Molecule.ai will enable Shuttle to train AI models that can predict molecular interactions and recognize patterns, thus transforming the drug discovery process [6][9] - This shift positions Shuttle as a leader in creating a feedback network where insights build upon each other, enhancing the overall discovery process [7][11] Industry Implications - The integration of AI in drug discovery is not just about speed but about comprehension, allowing for a deeper understanding of molecular behavior and potential side effects [8][9] - The ability to learn from past experiments will create a multiplier effect in drug discovery, enabling a scalable platform that can lead to multiple discoveries from a single insight [10][12] Future Outlook - The future of biotechnology may evolve beyond traditional definitions, with companies like Shuttle becoming hybrid entities that combine laboratory work with advanced algorithms [12][14] - The focus will shift from the number of patents filed to the improvement of AI models, indicating a new paradigm in measuring success in the biotech industry [12][14]

Core Insights - Artificial intelligence has significantly impacted various industries, with drug discovery being one of the most challenging areas for its application [1] Industry Summary - Drug discovery remains a complex field where molecules exhibit unpredictable behaviors, making it difficult for algorithms to accurately predict outcomes [1]

Core Viewpoint - Radiation therapy is a significant method in cancer treatment, known for its effectiveness but also for its aggressive nature [1] Group 1 - Radiation therapy is described as the "heavyweight" of cancer treatment, indicating its prominent role in the industry [1] - The effectiveness of radiation therapy is acknowledged, highlighting its importance in cancer care despite its harshness [1]

Core Insights - Shuttle Pharmaceuticals Holdings, Inc. has entered into a binding term sheet to acquire substantially all assets and liabilities of Molecule, a Canadian AI company, for a total purchase price of $10 million, payable in cash and shares [2][3][4] Company Overview - Shuttle Pharmaceuticals is a clinical-stage pharmaceutical company focused on enhancing cancer therapy outcomes by developing novel drugs that sensitize cancer cells to radiation therapy [4] - The company's mission is to advance precision medicine approaches to radiotherapy, improving treatment efficacy and patient quality of life [4] Acquisition Details - The acquisition will involve a total purchase price of $10 million, with the payment structure consisting of cash and Shuttle common stock, determined at Shuttle's discretion and contingent on performance milestones [2][3] - The transaction is subject to satisfactory completion of mutual due diligence and execution of final transaction documents [3] Strategic Importance - The acquisition is viewed as a strategic step to expand Shuttle's technological capabilities, particularly through Molecule's AI platform, which offers advanced tools for molecular modeling and predictive analytics [4]