Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 AKARI THERAPEUTICS, PLC (Exact name of registrant as specified in its charter) England and Wales 2834 98-1034922 (State or other jurisdiction of incorporation or organization) As filed with the Securities and Exchange Commission on November 17, 2025 Washington, D.C. 20549 FORM S-1 (Primary Standard Industrial Classification Code) (I.R.S. Employer Identification No.) 401 E Jackson St ...

Financial Performance - The company reported a loss from operations of $7.4 million for the three months ended September 30, 2025, a 153% increase compared to a loss of $2.9 million for the same period in 2024[169]. - The company reported a 14% decrease in loss from operations for the nine months ended September 30, 2025, totaling $14.0 million compared to $16.4 million for the same period in 2024[169]. - The net loss applicable to common shareholders for the three months ended September 30, 2025, was $6.4 million, compared to a net loss of $2.9 million for the same period in 2024[201]. - As of September 30, 2025, the company had $2.5 million in cash and an accumulated deficit of $259.3 million, with no revenue generated to date[202]. - The Company reported a net change in cash of $(115,000) for the nine months ended September 30, 2025, compared to $(1,599,000) for the same period in 2024[228]. - As of September 30, 2025, the Company had net cash used in operating activities of $(7,527,000), an improvement from $(10,428,000) in the same period of 2024[228]. - The Company may face substantial doubt regarding its ability to continue as a going concern within one year due to recurring losses and the need for additional capital[226]. Operating Expenses - Total operating expenses for the three months ended September 30, 2025, were $7.4 million, which includes a $5.18 million non-cash impairment loss on other intangible assets[169]. - Research and development expenses for the three months ended September 30, 2025, were $249,000, an increase of $106,000 compared to $143,000 for the same period in 2024[172]. - HSCT-TMA clinical development expenses decreased by $0.5 million and $1.5 million for the three and nine months ended September 30, 2025, respectively, compared to the same periods in 2024, due to the suspension of the AK901 clinical program[173]. - CMC expenses decreased by $0.4 million and $3.3 million for the three and nine months ended September 30, 2025, respectively, primarily due to the suspension of the pre-clinical PAS-nomacopan program[175]. - General and administrative costs increased by approximately $0.3 million and $0.5 million for the three and nine months ended September 30, 2025, respectively, mainly due to an increase in non-cash stock-based compensation[180][181]. Funding and Capital Structure - The company completed a registered direct offering on October 16, 2025, raising gross proceeds of $2.5 million by issuing 3,125,000 ADSs at a price of $0.80 each[164]. - The company entered into an Ordinary Share Purchase Agreement with White Lion Capital, allowing for the potential purchase of up to $25 million in newly issued Ordinary Shares[165]. - The Company entered into a placement agency agreement, paying $262,500 in cash for the 2025 Registered Direct Offering and granting warrants for 125,000 ADSs at an exercise price of $1.00 per ADS[208]. - Under the ELOC Purchase Agreement, the Company can require White Lion to purchase up to $25,000,000 in newly issued Ordinary Shares, subject to certain conditions[209]. - The Company has the right to control the timing and amount of sales of Ordinary Shares to White Lion, with a commitment period ending on August 29, 2028[210]. - The maximum number of Ordinary Shares that can be issued under the ELOC Purchase Agreement is capped at 13,039,369,358, representing 19.99% of the Company's outstanding shares[211]. - The Company issued August 2025 Notes with an aggregate purchase price of $3,011,000 and a principal amount of $3,763,750, with maturity dates ranging from August 15, 2026, to September 26, 2026[218]. - The Company has outstanding convertible notes and notes payable expected to result in principal payments of approximately $4.6 million as of September 30, 2025[231]. - The Company is seeking additional funding through equity and/or debt securities to continue operations, as it currently has no products approved for sale and does not generate revenue[222]. Management and Corporate Actions - The company has suspended internal development of legacy programs nomacopan and PAS-nomacopan to focus on the ADC platform[156]. - The company appointed Mr. Kameel Farag as Interim Chief Financial Officer, effective October 22, 2025, with a monthly cash fee of $18,000[162]. - The company recognized a gain on settlement of current liabilities of $0.8 million during the three months ended September 30, 2025[189]. - The company recognized an impairment loss related to in-process R&D of PHP 303 due to reprioritization of resources[182]. Research and Development - The company aims to establish AKTX-101 as a best-in-class Trop2-targeting ADC for treating various solid tumors[155]. - The company presented immune mechanism-of-action data for its novel ADC payload at the 2025 Society for Immunotherapy of Cancer Annual Meeting, indicating potential new treatment paradigms[161]. Accounting and Reporting - Management's discussion and analysis is based on unaudited condensed consolidated financial statements prepared in accordance with U.S. GAAP[234]. - No material changes to critical accounting policies and estimates have occurred since December 31, 2024[235]. - The company is classified as a smaller reporting company and is not required to provide certain market risk disclosures[236].

Core Insights - The novel spliceosome targeting payload, PH1, shows potential in inducing cancer cell cytotoxicity and activating anti-tumor immunity through various mechanisms [1][3] - The combination of Trastuzumab-PH1 ADC with anti-PD1 therapy significantly outperforms Kadcyla® with anti-PD1 in achieving complete tumor regressions (74% vs. 42%, p<0.05) [1][12] - Akari Therapeutics is advancing its lead ADC candidate, AKTX-101, which targets the Trop2 receptor and utilizes the PH1 payload, aiming to enter clinical trials soon [7][9] Company Overview - Akari Therapeutics is focused on developing next-generation spliceosome payload antibody drug conjugates (ADCs) [9] - The company’s innovative ADC platform allows for the generation and optimization of ADC candidates tailored to specific targets [9] - The PH1 payload is designed to disrupt RNA splicing in cancer cells, leading to cancer cell death and immune activation [9] Mechanism of Action - Trastuzumab-PH1 induces RNA mis-splicing, resulting in increased neoantigen generation and a subsequent rise in anti-cancer immune cells within the tumor microenvironment [4][12] - The combination therapy enhances immune responses, including the polarization of macrophages, increase in neutrophils, and expansion of B cell clones producing IgM antibodies [3][12] - The synergy between Trastuzumab PH1 and anti-PD1 therapy is attributed to their complementary effects on the immune system, particularly the expansion of gamma-delta T cell clones [3][12] Market Potential - The immuno-oncology therapeutic class is currently valued at approximately $50 billion per year, with the potential for significant growth through innovative therapies like those developed by Akari [1][4] - The unique results from the Trastuzumab-PH1 and anti-PD1 combination therapy could establish a new standard of care in cancer treatment, improving patient outcomes [6][12] Upcoming Events - Akari Therapeutics will host a live webcast on November 18, 2025, to discuss the presented data, providing insights for investors and analysts [1][8]

Core Insights - Akari Therapeutics is presenting data on its novel antibody drug conjugate (ADC) payload, PH1, at the 40th Annual Society for Immunotherapy of Cancer (SITC) Meeting, highlighting its immune mechanism-of-action and potential in oncology [1][2] Company Overview - Akari Therapeutics is focused on developing next-generation spliceosome payload ADCs, with its lead candidate, AKTX-101, targeting the Trop2 receptor on cancer cells [5][6] - The PH1 payload is designed to disrupt RNA splicing within cancer cells, showing preclinical efficacy in inducing cancer cell death and activating immune cells [5][6] Research Findings - The abstract presented at SITC indicates that the PH1 ADC, in combination with anti-PD-1, resulted in a higher rate of complete tumor regressions compared to a first-in-class ADC with a microtubule inhibitor payload [2] - The immune response stimulated by the PH1 ADC is attributed to neoantigen activation, which enhances the activity of antigen-presenting cells, B, and T-cells [2] - Notably, the combination of PH1 ADC and anti-PD-1 expanded the population of gamma-delta T cells, which are effective in tumor killing [2] Presentation Details - The oral and poster presentations will take place on November 7 and 9, 2025, at the Gaylord National Resort and Convention Center, with specific times and locations provided for attendees [3][4]

Core Insights - Akari Therapeutics is presenting new data on its novel antibody drug conjugate (ADC) payload, PH1, at the 40th Annual SITC Meeting, highlighting its immune mechanism-of-action and potential in oncology treatment [1][2]. Company Overview - Akari Therapeutics is focused on developing next-generation spliceosome payload ADCs, with its lead candidate, AKTX-101, targeting the Trop2 receptor on cancer cells [5]. - The PH1 payload is a spliceosome modulator designed to disrupt RNA splicing in cancer cells, showing preclinical efficacy in inducing cancer cell death and activating immune responses [5]. Research Findings - The abstract presented at SITC indicates that the PH1 ADC, in combination with anti-PD-1, resulted in a higher rate of complete tumor regressions compared to a first-in-class ADC with a microtubule inhibitor payload [2]. - The immune response stimulated by the PH1 ADC involves neoantigen activation, antigen-presenting cells, and T-cell activation, leading to enhanced therapeutic potential [2]. Presentation Details - The oral and poster presentations will provide further insights into the findings, with specific sessions scheduled for November 7 and November 9, 2025 [3][4].

Core Insights - Akari Therapeutics has formed a Scientific Advisory Board (SAB) and appointed Dr. Sara Hurvitz as its inaugural member, which is a significant step in advancing the company's scientific and clinical strategy [2][4] Company Overview - Akari Therapeutics is an oncology biotechnology company focused on developing novel payload antibody drug conjugates (ADCs) [1][9] - The company is expanding its ADC pipeline to include multiple targets, such as AKTX-101, which is a Trop2 ADC with a PH1 payload, and future programs like AKTX-102 with an undisclosed target [8][9] Leadership and Expertise - Dr. Sara Hurvitz is an internationally recognized expert in oncology, particularly in the clinical development of ADCs and targeted therapies for breast cancer [4][6] - She currently serves as Professor of Medicine and Division Head of Hematology/Oncology at the University of Washington School of Medicine and has a distinguished career in leading global clinical trials [5][6] Scientific Contributions - Dr. Hurvitz's expertise includes management of cancers at all stages, with a focus on neoadjuvant treatments and targeted therapies for various breast cancer types [2][4] - She has emphasized the transformative impact of ADCs in oncology, particularly in breast cancer, and is optimistic about Akari's preclinical data [2][4] Product Development - Akari's lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells and utilizes a novel PH1 payload designed to disrupt RNA splicing, which has shown significant activity in preclinical studies [9] - The company aims to advance its lead asset and other undisclosed targets with this innovative payload, which has demonstrated potential synergy with checkpoint inhibitors [9]

Core Insights - Akari Therapeutics has launched a new platform called CEO Corner, aimed at providing deeper insights into the company's press releases, corporate developments, and pipeline progress [2][3] - The CEO Corner will allow stakeholders to ask questions and suggest topics for future discussions, enhancing engagement and transparency [1][2] Company Overview - Akari Therapeutics is focused on developing next-generation spliceosome payload antibody drug conjugates (ADCs) for oncology applications [4] - The company's lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells and utilizes a proprietary linker to deliver a novel PH1 payload directly into tumors [4] - PH1 is designed to modulate RNA splicing within cancer cells, leading to cancer cell death and activation of immune responses, showing significant activity in preclinical studies compared to traditional ADCs [4] Product Development - AKTX-101 has demonstrated prolonged survival in preclinical models, both as a single agent and in combination with checkpoint inhibitors, indicating its potential for synergistic effects [4] - The company is actively generating validating data on the PH1 payload to further advance AKTX-101 and explore other undisclosed targets [4]

Core Points - Akari Therapeutics has entered into a definitive agreement for the issuance and sale of 3,125,000 American Depositary Shares (ADSs) at a price of $0.80 per ADS in a registered direct offering [1] - The gross proceeds from the offering are expected to be approximately $2.5 million, which will be used for working capital, general corporate purposes, and continued research and development [4] Offering Details - Ladenburg Thalmann & Co. Inc. is acting as the exclusive placement agent for the offering [2] - The company will also issue unregistered Series E and Series F Warrants to purchase up to 3,125,000 ADSs at an exercise price of $0.98 per share [3] - The offering is expected to close on or about October 16, 2025, subject to customary closing conditions [3] Research and Development Focus - The funds from the offering will be used to generate differentiated data on the novel ADC payload, which targets cancer cells and aims to highlight its unique action against cancer [4] - Akari's lead candidate, AKTX-101, utilizes a novel spliceosome modulator payload designed to disrupt RNA splicing within cancer cells, showing significant activity in preclinical studies [8][9] Company Overview - Akari Therapeutics is focused on developing next-generation spliceosome payload antibody drug conjugates (ADCs) [8] - The company aims to advance its lead asset, AKTX-101, and other undisclosed targets with its novel payload [9]

Core Insights - Akari Therapeutics has filed two new provisional patent applications with the USPTO, focusing on its novel immuno-oncology payload PH1 and its combination therapy with other immuno-oncology drugs [1][2][3] Patent Applications - The first patent application protects Akari's novel immuno-oncology payload PH1, which is a Thailanstatin analog, and its mechanism of action that activates the host immune system against cancer [1] - The second application covers a combination therapy of PH1 ADCs with other immuno-oncology drugs that alleviate checkpoint inhibition, demonstrating synergy in preclinical models [1][3] Strategic Goals - The patent filings are part of Akari's strategy to establish a new class of immuno-oncology ADC therapies, building on the success of checkpoint inhibitors [2] - The company aims to enhance its intellectual property estate to create long-term value for itself and potential partners [2] Clinical Implications - Akari's data suggest the potential for a new ADC paradigm targeting cancer through spliceosome modulation, which could improve clinical outcomes compared to existing therapies [4] - Checkpoint inhibitors currently benefit only 20-30% of patients, indicating a significant opportunity for Akari's innovative approach [4] Pipeline Development - Akari is expanding its ADC pipeline to include multiple targets, such as AKTX-101 (Trop2 ADC with PH1 payload) and future programs like AKTX-102 [5][6] - The lead candidate AKTX-101 has shown significant activity and prolonged survival in preclinical studies, with potential synergy with checkpoint inhibitors [6]

Core Insights - Akari Therapeutics, Plc is an oncology biotechnology company focused on developing novel payload antibody drug conjugates (ADCs) [1][2] - The company’s lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells and utilizes a proprietary linker to deliver a novel spliceosome modulator payload, PH1, designed to disrupt RNA splicing [2] - AKTX-101 has shown significant preclinical activity, inducing cancer cell death and activating immune cells, with potential synergy with checkpoint inhibitors [2] Presentation Details - Akari Therapeutics will present an abstract at the 40th Annual SITC Meeting, scheduled for November 5-9, 2025 [1] - The presentation titled "A Novel Splicing-Targeted ADC Payload Drives Immune Activation, Synergy with Checkpoint Inhibitors, and Enhanced Therapeutic Potential beyond Cytotoxicity" will be delivered by Dr. Satyajit Mitra [1] - The oral presentation is set for November 9, 2025, at 11:05 AM ET, with a poster presentation on November 7, 2025 [1]