Israel 2834 Not Applicable (Primary Standard Industrial Classification Code Number) As filed with the Securities and Exchange Commission on January 22, 2026 Registration No. 333-292528 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 AMENDMENT NO. 1 TO FORM F-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 REDHILL BIOPHARMA LTD. (Exact name of Registrant as specified in its charter) Not Applicable (Translation of Registrant's name into English) (State or other jurisdiction o ...

Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 As filed with the Securities and Exchange Commission on December 31, 2025 FORM F-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 REDHILL BIOPHARMA LTD. (Exact name of Registrant as specified in its charter) Not Applicable (Translation of Registrant's name into English) (Address, including zip code, and telephone number, including area code, of Registrant's principal executive offices) RedHill Biopharma In ...

Core Insights - Resistance to venetoclax, a $2.5 billion therapy for Chronic Lymphocytic Leukemia (CLL), is becoming a significant therapeutic challenge as leukemic cells persist despite combination therapies [1][3] - New in vivo studies indicate that the addition of opaganib, a potent sphingosine kinase 2 (SPHK2) inhibitor, to venetoclax can reduce CLL cell counts by 50% compared to controls, suggesting its potential as an add-on therapy for venetoclax-resistant CLL [1][2] - Opaganib has demonstrated a favorable safety and tolerability profile in over 470 clinical trials and is being evaluated for multiple indications, including oncology and viral infections [1][9] Company Overview - RedHill Biopharma Ltd. is a specialty biopharmaceutical company focused on the development and commercialization of drugs for gastrointestinal diseases, infectious diseases, and oncology [12] - The company promotes the FDA-approved drug Talicia for treating Helicobacter pylori infections and is advancing several late-stage clinical programs, including opaganib [12][13] - Opaganib is currently undergoing a Phase 2 clinical trial in combination with darolutamide for advanced prostate cancer, highlighting its broad therapeutic potential [1][7] Product Insights - Venetoclax, approved by the FDA in 2016, is a first-in-class BCL-2 inhibitor that has become a cornerstone of CLL therapy, achieving sales of approximately $2.5 billion in 2024 [3] - Opaganib is a first-in-class, orally administered drug with anticancer, anti-inflammatory, and antiviral activities, targeting multiple indications including various cancers and viral diseases [6][10] - The drug has received orphan-drug designations from the FDA for cholangiocarcinoma and neuroblastoma, indicating its potential in treating rare diseases [7]

Core Insights - RedHill Biopharma has undergone a significant strategic, financial, and operational overhaul, leading to strong progress in its business operations and financial results for the first half of 2025 [4][3]. Commercial Highlights - Talicia generated net revenues of $3.8 million in the first half of 2025, an increase from $3.5 million in the same period of 2024, with U.S. net revenues of $3.3 million compared to $3.0 million in the prior year [5][20]. - The commercial team has achieved formulary wins securing an additional 8 million covered lives, bringing the total to over 204 million lives [20]. - The company is pursuing geographic expansion with a potential UK Marketing Authorization Application approval expected this year [21]. - Talicia surpassed 100,000 prescriptions, reflecting a positive patient experience with minimal refunds claimed [21]. R&D Highlights - The Bayer-supported Phase 2 study of opaganib in combination with darolutamide for advanced prostate cancer has commenced patient recruitment [8][32]. - The FDA has provided positive feedback on the pathway to approval for the RHB-204 Crohn's disease program, which aims to be the first clinical trial in a defined MAP-positive patient population [8][33]. - RedHill's pipeline includes multiple externally funded programs targeting significant market opportunities in oncology, infectious diseases, and gastrointestinal disorders [23][35]. Financial Highlights - Net revenues for the first half of 2025 were $4.1 million, a 59% increase from $2.6 million in the first half of 2024 [5][12]. - Gross profit doubled to $2.5 million compared to $1.2 million in the same period of 2024, driven by higher revenues and cost-free royalty contributions [7][10]. - Operating loss decreased to $4.4 million from $8.4 million in the first half of 2024, primarily due to higher gross profit and reduced operating expenses [10][12]. - The company reported a net loss of $4.1 million for the first half of 2025, compared to a net loss of $3.1 million in the same period of 2024 [12]. Liquidity and Financing - As of June 30, 2025, the cash balance was $3 million, with a reduction in cash burn by 19% following a previous year's 74% reduction [8][14]. - The company has secured up to $60 million in an out-licensing deal for RHB-102 with Hyloris Pharma [4][8]. - Enhanced liquidity was achieved through an Any Market Purchase Agreement, allowing the company to sell up to $10 million of American Depositary Shares [15][16].

Core Insights - The article discusses the initiation of a Phase 2 study evaluating the combination of opaganib and darolutamide in patients with advanced prostate cancer, sponsored by ANZUP and supported by Bayer and Ramsay Hospital Research Foundation [1][2] - Prostate cancer is a significant global health issue, with approximately 1.5 million new cases and nearly 400,000 deaths annually, representing a market worth around $12 billion [1][5] Study Overview - The Phase 2 study will involve 60 participants and is designed to assess the efficacy of opaganib in overcoming resistance to standard androgen receptor pathway inhibitors [2][3] - The study will utilize the PCPro lipid biomarker test to identify patients with poor prognosis who may benefit from the treatment combination [3][5] - The primary endpoint of the study is to improve 12-month radiographic progression-free survival (rPFS), with several secondary and exploratory endpoints also being evaluated [3] Prostate Cancer Context - Prostate cancer is the second most diagnosed cancer globally, with a significant increase in cases, nearly 120% from 1990 to 2019 [6] - The survival rates for prostate cancer vary significantly by stage, with a 100% five-year survival rate for Stage 1, dropping to 28% for Stage 4 [7] Androgen Receptor Pathway Inhibitors (ARPI) - ARPI is a key therapeutic strategy for treating castration-resistant prostate cancer, targeting male hormones that promote cancer cell growth [8] - Darolutamide is one of the key therapeutic options in this category, alongside enzalutamide and apalutamide [8] Opaganib Profile - Opaganib is an investigational drug with anticancer, anti-inflammatory, and antiviral properties, targeting multiple indications including various cancers [9][10] - The drug works by inhibiting multiple pathways and has shown potential in enhancing the efficacy of androgen receptor signaling inhibitors [4][10] Company Background - RedHill Biopharma is focused on developing and commercializing drugs for gastrointestinal diseases, infectious diseases, and oncology, with opaganib being a key part of its late-stage development programs [18]