Theophylline

Abstracts include a presidential plenary-selected Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, along with 10 other abstractsMORRISTOWN, N.J., April 30, 2025 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Intercept), part of the Alfasigma Group, today announced 11 submitted abstracts have been accepted for presentation at Digestive Disease Week 2025, including oral presentations of data from a Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, and investigational data for INT-787, a next-generation FXR agonist. The conference will be held from May 3-6 in San Diego. The abstracts showcase the Company’s breadth of research in the gastrointestinal (GI) and hepatology therapeutic areas. The data encompass multiple areas of high unmet need, including primary biliary cholangitis (PBC); primary sclerosing cholangitis (PSC); severe alcohol-associated hepatitis (sAH), a liver disease increasing in prevalence, especially among women; and chronic intestinal pseudo-obstruction (CIPO), a rare condition characterized by severe impairment of intestinal activity. “We look forward to sharing details of our clinical-development program progress with the scientific community, including our ongoing Phase 2 study of a potential first-in-class treatment for severe alcohol-associated hepatitis,” said Sangeeta Sawhney, M.D., Senior Vice President, Global Head, GI Therapeutic Area, Alfasigma. “We're also going to share the first six-year data for a second-line therapy for PBC, which gives insights into long-term safety and effectiveness." Presentations by Intercept and Alfasigma at DDW 2025: Oral Presentations “COMBINED EFFECT OF OBETICHOLIC ACID AND BEZAFIBRATE IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INADEQUATE RESPONSE OR INTOLERANCE TO URSODEOXYCHOLIC ACID: 6-MONTH RESULTS FROM A PHASE 2 TRIAL” (Presentation #4)Session: AASLD Presidential PlenarySaturday, May 3, 9:15 AM ETChristophe Corpechot, Vaclav Hejda, Heng Zou, Antonio Civitarese, Alejandra Villamil, Frederik Nevens “FXR AGONIST INT-787 INHIBITS INFLAMMATION, FIBROSIS, SENESCENCE, AND APOPTOSIS ARREST IN HUMAN CHOLANGIOCYTES MODELING PSC” (Presentation #879)Session: Cutting-Edge Insights into PSC: From Mechanisms to TherapiesMonday, May 5, 4:45 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari Poster Presentations “OBETICHOLIC ACID NORMALIZES INFLAMMATORY BIOMARKERS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS” (Poster #Sa1500)Session: Liver Inflammation and ImmunobiologySaturday, May 3, 12:30 PM ETDavid E. Jones, Christopher L. Bowlus, Arash Thranian, Mary Erickson, Jing Li, Christopher Gasink, Robert G. Gish “US POPULATION–BASED EPIDEMIOLOGY OF PRIMARY BILIARY CHOLANGITIS: EXAMINATION OF PATIENT CHARACTERISTICS AND INCIDENCE OF HEPATIC OUTCOMES IN A US HEALTHCARE CLAIMS DATABASE” (Poster #Su1675)Session: Health Disparities in Patients with Liver DiseaseSunday, May 4, 12:30 PM ETAparna Goel, Bridget L. Balkaran, Chris White, Radhika Nair, Anne Chiplin, Jing Li, Jayashri Desai, Joanna P. MacEwan “REAL-WORLD ADHERENCE TO OBETICHOLIC ACID THERAPY FOR PRIMARY BILIARY CHOLANGITIS” (Poster #Mo1626)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETRobert G. Gish, Joanna P. MacEwan, Jennifer Hernandez, Radhika Nair, Jing Li, Darren Wheeler, Anh Singhania, Leona Bessonova “PATIENTS WITHOUT BASELINE PRURITUS WHO INITIATE TREATMENT WITH OCA HAVE SIMILAR RISK OF DEVELOPING TREATMENT-EMERGENT PRURITUS AS THOSE WHO ARE NOT ON TREATMENT WITH OCA” (Poster #Mo1618)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETDavid Jones, Aparna Goel, Ann Moore, Jing Li, Darren Wheeler, Christopher White, and David W. Victor III “STABILIZATION OF ENHANCED LIVER FIBROSIS AND LIVER STIFFNESS MEASURES IN THE OPEN-LABEL EXTENSION OF THE PHASE 3 POISE TRIAL OF OBETICHOLIC ACID FOR THE TREATMENT OF PRIMARY BILIARY CHOLANGITIS” (Poster #Mo1667)Session: Non-Invasive Assessment of Liver DiseaseMonday, May 5, 12:30 PM ET Robert G. Gish, Darren Wheeler, Jing Li, Christopher Gasink, Alan Bonder “FARNESOID X RECEPTOR AGONIST INT-787 PROTECTS HUMAN LIVER ORGANOIDS FROM ALCOHOL-INDUCED INJURY” (Poster #Su1618)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari “FARNESOID X RECEPTOR AGONIST INT-787 EXHIBITS HIGH INTESTINAL LOCALIZATION” (Poster #Su1635)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETJennifer Burkey, Sanjay Kansra, Antonio Macchiarulo, Kenneth Brouwer, Luciano Adorini, Mary Erickson, Roberto Pellicciari “PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF OBETICHOLIC ACID AND BEZAFIBRATE IN HEALTHY VOLUNTEERS” (Poster #Mo1628)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETJennifer Burkey, Karen Brown, Heng Zou, Jennifer Boston, Mary Erickson “DEVELOPMENT OF A DE NOVO CLINICAL OUTCOME ASSESSMENT FOR CHRONIC INTESTINAL PSEUDO-OBSTRUCTION" (Poster #Mo1258)Session: Patient Report and Clinical Outcomes: IBD, GERC, Functional Disorders, Other Monday, May 5, 12:30 PM ETMadhusudan Grover, Jan Tack, Sara Manzoni, Elena Pasquali, Valeria Scuderi, Vincenzo Stanghellini More information about these presentations will be made available after the respective embargoes, as set by the DDW organizers, are lifted for each presentation. A full list of sessions at DDW 2025 is available at www.ddw.org. Attendees of DDW can visit Intercept at booths #2011 and #2411 throughout the meeting. About Digestive Disease WeekDigestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 3-6, 2025. The meeting showcases more than 5,600 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org. About Primary Biliary CholangitisPrimary biliary cholangitis (PBC) is a rare, progressive and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent (approximately 1 in 10,000) in women over the age of 40. PBC causes bile acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant or death. About Severe Alcohol-Associated Hepatitis (sAH)Alcohol-related liver disease (ALD) as a cause of chronic liver disease is on the rise in the U.S. and is currently the leading indication for liver transplant listing overall in the U.S. Patients with severe alcohol-associated hepatitis (sAH) are now younger, with an increased representation of females compared to past decades, reflecting changing patterns of alcohol consumption in the U.S. Currently, there are no medicines with an approved indication to treat patients with sAH. About Primary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is a rare, life-threatening, chronic cholestatic liver disease characterized by progressive destruction of bile ducts that leads to the development of cirrhosis and end-stage liver disease or cancer in a majority of patients. About the Investigational Obeticholic Acid-Bezafibrate CombinationIntercept has two ongoing Phase 2 studies (747-213 / NCT04594694, 747-214 / NCT05239468) that are exploring a range of therapeutic doses for the combination of obeticholic acid (OCA) and bezafibrate for the potential treatment of individuals with PBC. Obeticholic acid, a farnesoid X receptor (FXR) agonist, is marketed by Intercept as OCALIVA in the United States for the treatment of PBC (see below for full indication and Important Safety Information). Bezafibrate, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is not approved in the United States for any indication. FXR and PPAR are distinct pathways that each play a role in PBC. Simultaneously targeting both pathways may offer the greatest potential to impact bile acid synthesis, metabolism, and clearance that underly cholestatic liver diseases. Published studies establish a clinical proof-of-concept which suggests that the combination of obeticholic acid and bezafibrate may provide additive clinical efficacy and tolerability benefits in the treatment of PBC. Obeticholic acid-bezafibrate combination therapy is investigational; safety and efficacy have not been established. About OCALIVA (obeticholic acid)OCALIVA, a farnesoid X receptor (FXR) agonist, is indicated for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis orwith compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. IMPORTANT SAFETY INFORMATION WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis. OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension, or experience clinically significant hepatic adverse reactions while on treatment. Contraindications OCALIVA is contraindicated in patients with: decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation eventcompensated cirrhosis who have evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)complete biliary obstruction Warnings and Precautions Hepatic Decompensation and Failure in PBC Patients with Cirrhosis Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with cirrhosis, either compensated or decompensated. Among post-marketing cases reporting it, median time to hepatic decompensation (e.g., new onset ascites) was four months for patients with compensated cirrhosis; median time to a new decompensation event (e.g., hepatic encephalopathy) was 2.5 months for patients with decompensated cirrhosis. Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dosage for that patient population; however, cases of hepatic decompensation and failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dosage. Hepatotoxicity was observed in the OCALIVA clinical trials. A dose-response relationship was observed for the occurrence of hepatic adverse reactions including jaundice, worsening ascites, and primary biliary cholangitis flare with dosages of OCALIVA of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with OCALIVA in two 3-month, placebo-controlled clinical trials in patients with primarily early stage PBC. Routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether drug discontinuation is needed. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time to determine whether drug discontinuation is needed. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy), have compensated cirrhosis and develop evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. If severe intercurrent illness occurs, interrupt treatment with OCALIVA and monitor the patient’s liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting OCALIVA treatment. Severe Pruritus Severe pruritus was reported in 23% of patients in the OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arm in a 12-month double-blind randomized controlled clinical trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. Consider clinical evaluation of patients with new onset or worsening severe pruritus. Management strategies include the addition of bile acid binding resins or antihistamines, OCALIVA dosage reduction, and/or temporary interruption of OCALIVA dosing. Reduction in HDL-C Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C). Dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in OCALIVA-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to OCALIVA after one year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment. Adverse Reactions The most common adverse reactions (≥5%) are pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema. Drug Interactions Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of OCALIVA. If taking a bile acid binding resin, take OCALIVA at least four hours before or four hours after taking the bile acid binding resin, or at as great an interval as possible.Warfarin The International Normalized Ratio (INR) decreased following coadministration of warfarin and OCALIVA. Monitor INR and adjust the dose of warfarin, as needed, to maintain the target INR range when co-administering OCALIVA and warfarin.CYP1A2 Substrates with Narrow Therapeutic Index Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index (e.g., theophylline and tizanidine) is recommended when co-administered with OCALIVA.Inhibitors of Bile Salt Efflux Pump Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts including taurine conjugate of obeticholic acid in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitor serum transaminases and bilirubin. Please click here for Full Prescribing Information, including boxed WARNING. To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. About InterceptIntercept, part of the Alfasigma Group since 2023, focuses on the development and commercialization of novel therapeutics to treat serious liver and GI diseases, including primary biliary cholangitis (PBC) and severe alcohol-associated hepatitis (sAH). Intercept owns the commercial rights to OCALIVA in the U.S. market. For more information, please visit www.interceptpharma.com or connect with the Company on LinkedIn, and X (formerly Twitter). About Alfasigma Alfasigma is a global pharmaceutical company founded over 75 years ago in Italy, where it is headquartered (in Bologna and Milan). The Group operates in over 100 markets spanning Europe, North and South America, Asia, and Africa. It has offices in many countries, including Italy, the United States (US), Spain, Germany, Mexico, and China; production sites in Italy, Spain, and the US; and R&D labs in Italy (Pomezia and Bergamo). Alfasigma employs approximately 4,000 people dedicated to research, development, production, and distribution of medicinal products contributing to its mission to provide better health and a better quality of life for patients, caregivers, and healthcare providers. It focuses on three main therapeutic areas: Gastroenterology/Hepatology, Vascular, and Rheumatology. Its portfolio spans from primary care to specialty care, rare disease medications, and consumer health products, including medical foods and nutraceuticals. For more information, please visit www.alfasigma.com or connect with the Company on LinkedIn, ContactFor more information about Intercept, please contact: media@interceptpharma.com

Our analysis of February data reveals key trends in global clinical-stage biopharmaceutical financing. For contextual understanding, we recommend beginning with the following article. Highlights of February 2025: Biopharmaceutical Clinical-Stage Drug Investment, Financing, and Collaboration Deals (1) 11. Kyorin and Cyrano Therapeutics Enter into an Option Agreement for the Development and Commercialization of CYR-064 in Japan On February 14, 2025, Kyorin Pharmaceutical Co., Ltd. and Cyrano Therapeutics, Inc. announced the signing of an option agreement for the novel drug CYR-064, which is designed to treat hyposmia following viral infections. Under the terms of this agreement, Kyorin has obtained the rights to develop and commercialize CYR-064 in Japan and will pay an option fee. Once the option is exercised and a licensing agreement is signed, Kyorin will also provide Cyrano with an upfront payment, milestone payments based on development and commercialization progress, and royalties calculated as a percentage of net sales after the product is launched. CYR-064 is a patented intranasal formulation of theophylline, a broad-spectrum phosphodiesterase inhibitor (PDEi), which increases intracellular cAMP levels by inhibiting cAMP degradation, thereby enhancing the excitability of olfactory neurons. This provides a potential therapeutic pathway for treating hyposmia following viral infections and other olfactory disorders. Currently, CYR-064 is undergoing a Phase II clinical trial in the United States, with trial data expected in the second half of 2025. Guided by its long-term vision "Vision 110," Kyorin Pharmaceutical is committed to creating high-value new drugs that meet medical needs. By actively leveraging open innovation strategies, Kyorin plans to continuously launch new drugs. This collaboration with Cyrano is part of its strategic implementation, aiming to accelerate the development and commercialization of CYR-064 in the Japanese market to address unmet medical needs. For the fiscal year ending in March 2025, this agreement is not expected to have a significant impact on Kyorin's business performance. However, with further development of CYR-064 and its potential market success, Kyorin anticipates positive financial returns in the coming years. Meanwhile, this collaboration also opens up new prospects for finding effective treatments for hyposmia following viral infections on a global scale. 12. Royalty Pharma Invests $250 Million to Support Biogen's Lupus Drug Litifilimab Development Royalty Pharma has entered into a $250 million agreement with Biogen to support the development of Biogen's late-stage experimental lupus drug litifilimab. Under the terms of the agreement, Biogen will receive this amount over the next six quarters. In return, if the drug achieves specific regulatory milestones, Royalty Pharma will receive undisclosed milestone payments and a mid-single-digit royalty on global sales. This transaction not only enhances Royalty Pharma's product portfolio but also brings more opportunities for potential revenue. Litifilimab is an anti-BDCA2 antibody currently in Phase III trials for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). The drug has demonstrated significant reduction in skin disease activity in the Phase II LILAC study, showing effective relief of skin symptoms in CLE patients compared to the placebo group at the primary endpoint. If approved by 2030, litifilimab is projected to achieve up to $750 million in global sales. This potential allows Biogen to use the funds to further advance its development process. Currently, the SLE market is dominated by generic drugs, with only a few targeted biologics approved by the U.S. Food and Drug Administration (FDA) in the past fifty years, such as GSK's Benlysta (belimumab) and AstraZeneca's Saphnelo (anifrolumab). In contrast, the CLE market is even more innovation-starved, with this form of lupus primarily affecting the skin, causing inflammation, rashes, and lesions. The successful development of litifilimab could change this status quo and provide new treatment options for patients. 13. Tivic Health Acquires Statera Biopharma's TLR5 Agonist Entolimod™ to Expand Its Therapeutic Pipeline Tivic Health Systems, Inc. has announced the acquisition of global exclusive rights to the late-stage Toll-like receptor 5 (TLR5) agonist Entolimod™ from Statera Biopharma for the treatment of acute radiation syndrome (ARS). In addition, Tivic has obtained exclusive options for five additional indications and clinical uses of Entolimod and its derivative Entalasta™. This extensive licensing agreement transforms Tivic into a diversified therapeutic company with complementary bioelectronic and biologic candidates in its clinical pipeline. As the lead candidate in the licensed portfolio, Entolimod is a TLR5 agonist specifically designed for the treatment of ARS. According to data from market research firm CoherentMI, the global ARS market was valued at $5.2 billion in 2024 and is projected to grow at a compound annual growth rate of 5% from 2024 to 2031. Entolimod and its immune-optimized derivative Entalasta have undergone over forty animal and human trials and received approximately $140 million in investment. The FDA has granted Entolimod Fast Track and Orphan Drug designations for the prevention or treatment of ARS and to prevent death following a potentially lethal dose of total-body ionizing radiation after a radiological disaster. Animal studies for ARS have shown that a single dose of Entolimod administered 25 hours after exposure to a lethal level of radiation can triple survival rates. The drug is effective without additional supportive care, demonstrating gastrointestinal protective properties and no dose-limiting toxicity even at the highest doses. Other studies have also shown its potential in applications such as immunosenescence, lymphocyte exhaustion, neutropenia, vaccine enhancement, and chronic radiation syndrome. Under the agreement, Tivic will initially pay Statera $1.2 million in equity consideration and $300,000 in cash for the use of Entolimod in treating ARS. Tivic has the option to add one or more indications and expand its licensing scope to Entolimod's derivative Entalasta by exercising the exclusive options granted in the agreement. Future potential payments will be royalty and milestone-driven, ensuring alignment with the clinical and commercial success of Entolimod and subsequent Entalasta. The agreement structure allows Tivic to strategically manage its investment while maximizing shareholder returns. To establish Tivic's biopharmaceutical capabilities and advance the product candidates toward commercialization, some members of Statera's team will join Tivic. The transaction also includes exclusive rights and options to over sixty patents and pending patents, related proprietary technology, and ownership of previously manufactured and tested materials. Craft Capital Management LLC served as the sole investment banking firm in this deal. With these resources integrated, Tivic is steadily moving toward becoming a leading biotherapeutic company. 14. Oramed Pharmaceuticals Announces Formation of OraTech Pharmaceuticals to Accelerate Development and Commercialization of Oral Insulin Oramed Pharmaceuticals Inc., a clinical-stage pharmaceutical company focused on the development of oral drug delivery platforms, recently announced that it will transfer its proprietary Protein Oral Delivery (POD™) technology to a new joint venture, OraTech Pharmaceuticals Inc., through a definitive agreement. This move is aimed at accelerating the development and commercialization of Oramed's oral insulin ORMD-0801 and other innovative oral drug delivery technologies based on the POD™ platform. In this transaction, Oramed will transfer its proprietary oral insulin and POD™ technology, along with other pipeline assets, to OraTech. Oramed shareholders will receive a majority stake in the new entity, allowing them to directly participate in its future success. Additionally, under the terms of the agreement, Oramed and HTIT will jointly invest $75 million, with Oramed contributing $15 million and HTIT contributing $60 million. This funding will provide OraTech with the necessary resources to advance product development, commercialization, and clinical progress. OraTech will leverage HTIT's expertise in capsule manufacturing and cost-effective production capabilities to establish a robust, reliable, and scalable supply chain to support clinical trials and commercial efforts. HTIT will also provide a supply agreement for the oral insulin capsules. Furthermore, OraTech plans to relaunch the pivotal Phase III clinical trial in the United States and advance the registration of oral insulin in the U.S. and other countries. In China, OraTech will receive royalties from the sales of oral insulin, while HTIT will be responsible for submitting marketing authorization applications and preparing for commercialization. 15. AdvanCell and Eli Lilly Expand Collaboration to Advance Cancer Targeted Alpha Therapy On February 10, 2025, AdvanCell announced that its strategic partnership with Eli Lilly and Company has been further expanded. This collaboration aims to research and develop innovative treatments for various types of cancer. The partnership not only recognizes AdvanCell's leadership in the field of Pb-212 targeted alpha therapy but also lays the foundation for a long-term collaboration between the two companies. Under the new cooperation agreement, both parties will utilize AdvanCell's proprietary Pb-212 production technology and radiopharmaceutical development infrastructure, as well as Eli Lilly's drug candidates and extensive drug development experience, to jointly advance the development of more targeted alpha radiopharmaceutical therapies and accelerate their clinical progress. AdvanCell's technological advantages and its infrastructure established in Australia to expedite early clinical trials enable it to quickly move novel radiotherapeutic drugs containing Pb-212 from the discovery phase to clinical trials. AdvanCell is currently conducting a Phase I/II trial for ADVC001, a potentially best-in-class targeted alpha therapy for metastatic prostate cancer. The trial aims to assess the safety and efficacy of the Pb-212-based radiopharmaceutical therapy. The core product ADVC001 is designed to bind to PSMA (a cell surface target highly expressed in prostate cancer) and has demonstrated potential best-in-class characteristics in preclinical studies. This collaboration is expected to accelerate the development of ADVC001, bringing new hope to patients with prostate cancer. As the partnership between AdvanCell and Eli Lilly continues to deepen, both parties are committed to achieving new breakthroughs in cancer treatment. By integrating their respective strengths and technologies, the two companies will not only accelerate the clinical progress of existing projects but also potentially open up new therapeutic pathways. For cancer patients who do not respond well to traditional therapies, targeted alpha therapy offers a more precise and less side-effect-prone treatment option. In the future, with the emergence of more research results, it is expected that more patients will benefit from this innovative cancer treatment method. 16. OliX and Eli Lilly Reach Global Licensing Agreement to Develop New Therapies for MASH and Other Cardiometabolic Indications On February 10, 2025, OliX Pharmaceuticals announced a global licensing agreement with Eli Lilly and Company. This cooperation aims to jointly develop and commercialize OliX's OLX75016, a Phase I candidate drug primarily targeting metabolic-associated fatty liver hepatitis (MASH) and other cardiometabolic indications. Under the terms of the agreement, OliX will receive an upfront payment from Eli Lilly to support the ongoing Phase I clinical trial in Australia. OLX75016 originates from robust targets identified through genome-wide association studies (GWAS), a method that can identify genomic variations in large populations. In preclinical studies, OliX has demonstrated the efficacy of OLX75016 in treating MASH, liver fibrosis, and other cardiometabolic indications. Currently, OliX is developing OLX75016 as a novel therapy for MASH with liver fibrosis and other cardiometabolic conditions. OliX Pharmaceuticals is a clinical-stage pharmaceutical company focused on developing treatments for various diseases using its proprietary RNAi technology. The company's core RNAi platform—Asymmetric siRNA (asiRNA)—is a unique gene-silencing technology based on RNA interference (RNAi) and is considered one of the most effective gene-silencing technologies currently available. Using this proprietary asiRNA technology, OliX has developed cell-penetrating asiRNA (cp-asiRNA), a therapeutic RNAi platform that effectively targets diseases such as proliferative scar formation, dry and wet age-related macular degeneration (AMD), and subretinal fibrosis. In addition to cp-asiRNA, OliX has also developed another therapeutic RNAi platform, GalNAc-asiRNA, specifically for targeting various liver diseases. This collaboration with Eli Lilly not only advances the development of OLX75016 but also further solidifies OliX's position in the biopharmaceutical field, demonstrating its commitment to addressing unmet medical needs through innovative technologies. As research and development progresses, it is anticipated that more new therapies based on these advanced technologies will emerge, bringing hope to patients worldwide. 17. Kineta Restructures Portfolio Ahead of Merger with TuHURA Ahead of its merger with TuHURA Biosciences, Kineta has made significant adjustments to its portfolio. To streamline its investments, Kineta decided to sell its collaboration deals with Genentech and Merck & Co. to an investment company and transferred its pain treatment candidate drug KCP506 to Pacira Pharmaceuticals, while also terminating its cooperation agreement with GigaGen. TuHURA purchased Kineta for $15 million, with $5 million allocated to secure the exclusivity agreement. This acquisition enabled TuHURA to acquire Kineta's Phase II checkpoint inhibitor. In 2018, Genentech paid Kineta a $5 million upfront payment to obtain the rights to a small molecule modulator and set milestone payments of up to $96 million. The collaboration was expanded in 2020 to support the early development phase of a pain treatment candidate drug. On the other hand, Kineta inherited a collaboration with Merck from its merger with Yumanity Therapeutics, which obtained a preclinical drug candidate for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia from Yumanity in 2020. In 2023, Kineta received a $5 million milestone payment from Merck, with up to $255 million still pending. KCP506 is an α9α10 nicotinic acetylcholine receptor (nAChR) antagonist that Kineta is developing for the treatment of chronic neuropathic pain. Kineta initiated a Phase II trial for this drug. Subsequently, Kineta agreed to sell KCP506 to Pacira Pharmaceuticals for $450,000, marking the end of Kineta's further development of KCP506. A subsidiary of HealthCare Royalty Partners, HCRX Investments Holdco, reached an agreement with Kineta covering Kineta's licensing deals with Genentech and Merck, as well as its role in an agreement with Fair Therapeutics related to cystic fibrosis. This move will help Kineta focus its resources on the development of other key projects. Finally, Kineta decided to terminate its option and licensing agreement with GigaGen, which originally granted Kineta the rights to a CD27 drug program. By terminating this agreement, Kineta not only returned all rights to GigaGen but also waived its obligation to pay a $180,000 fee. This strategic retreat allows Kineta to concentrate more on the upcoming merger and the development of its core business. 18. Fosun Pharma and Dr. Reddy's Reach Licensing Agreement for HLX15 in Europe and the U.S. On February 6, 2025, Fosun Pharma announced a licensing agreement with Dr. Reddy's Laboratories for HLX15, a biosimilar to daratumumab, an anti-CD38 monoclonal antibody under development. HLX15 is a recombinant human anti-CD38 monoclonal antibody injection intended for the treatment of multiple myeloma and other hematologic malignancies. Under the agreement, Dr. Reddy's will obtain exclusive commercialization rights to the drug in 43 countries and regions, including 42 European countries and the United States. The collaboration aims to expand the drug's market coverage and provide advanced biologics to more patients. According to the terms of the agreement, Fosun Pharma will be responsible for the development, production, and commercial supply of HLX15 and may receive up to $131.6 million in funding from Dr. Reddy's, including a $33 million upfront payment and additional milestone payments. Additionally, Fosun Pharma will receive royalties based on annual net sales. This arrangement not only provides Fosun Pharma with the necessary cash flow to support its ongoing research and development but also enhances its competitiveness in the global market. HLX15, as a biosimilar, primarily works by targeting and inhibiting the function of the CD38 protein to combat multiple myeloma. CD38 is a protein highly expressed on the surface of certain cancer cells, and monoclonal antibodies targeting it can effectively identify and destroy these cells while minimizing impact on normal tissues. Therefore, HLX15 is expected to become an important option for treating such diseases. 19. Relmada Therapeutics Acquires Potential Tourette Syndrome Therapy Sepranolone from Asarina Pharma AB On February 6, 2025, Relmada Therapeutics announced the acquisition of Sepranolone from Asarina Pharma AB, a therapeutic asset for Tourette Syndrome (TS) and other compulsive-related disorders, ready to enter Phase IIb clinical trials. Sepranolone (isoallopregnanolone) is a first-in-class GABAA modulatory steroid antagonist (GAMSA) that selectively acts on the GABAA pathway, aiming to counteract the effects of allopregnanolone on TS and other compulsive disorders. An open-label Phase IIa randomized study showed that Sepranolone has the potential to improve TS symptoms, as measured by changes in the Yale Global Tic Severity Scale (YGTSS). In the 12-week study, Sepranolone not only reduced the primary clinical endpoint of tic severity by 28% (p=0.051) compared to standard care alone but also achieved positive results in four key secondary endpoints, including a 69% improvement in quality of life, a 50% reduction in functional impairment, and a 44% reduction in premonitory urges. Additionally, the drug did not exhibit off-target central nervous system effects or systemic adverse effects, which is a significant advantage for central nervous system disorders requiring long-term use and potentially severe side effects. Under the terms of the agreement, Relmada acquired global ownership of Sepranolone from Asarina Pharma AB for €3 million, completing the transaction through an asset purchase agreement. This acquisition reflects Relmada's mission to find solutions for refractory central nervous system diseases and its strategic goal of enhancing shareholder value by identifying and developing innovative compounds. Relmada will continue to evaluate additional products and strategic opportunities and expects to update investors on the next steps for Sepranolone's development later in 2025. With further clinical data support, if Sepranolone successfully transitions to later-stage clinical trials and ultimately receives approval, it is expected to become one of the first-line treatments for Tourette Syndrome, bringing new hope to patients. 20. Acelyrin Terminates Izokibep Program, Affibody Regains Drug Development Rights In 2021, Acelyrin acquired the license for izokibep with a $25 million upfront payment and committed to milestone payments of up to $280 million. Izokibep is an IL-17A inhibitor with a molecular weight only about one-eighth that of a typical antibody, exhibiting extremely high affinity for IL-17A and capable of specifically binding to both subunits of IL-17A as well as albumin in the serum. However, less than two years later, despite raising $540 million through an initial public offering to fund the late-stage trials of izokibep across multiple indications, Acelyrin ultimately decided to cease investment in the drug. Izokibep achieved the primary endpoint in a Phase III clinical trial for the treatment of hidradenitis suppurativa (HS), demonstrating a 33% reduction in abscesses and inflammatory nodules by 75% or more in patients, compared to 21% in the placebo group. Despite these positive results, Acelyrin chose to discontinue investment in this indication. Additionally, after achieving success in psoriatic arthritis (PsA), Acelyrin also withdrew its investment, retaining only uveitis as the final active development area for izokibep. However, the Phase IIb/III trial in this area failed to meet its primary and secondary endpoints. With Inmagene Biopharmaceuticals terminating the agreement covering Asian countries, including China and South Korea, the responsibility for izokibep will now fall entirely on Affibody in Sweden. Affibody's CEO, David Bejker, stated that he believes his company can better capitalize on the potential of izokibep than its former partner, particularly in the field of dermatology and for patients severely affected by hidradenitis suppurativa. This indicates Affibody's confidence in the potential of its product and its determination to regain control of the project. 21. Vanda Pharmaceuticals and AnaptysBio Reach Global Exclusive Licensing Agreement for IL-36R Antagonist Imsidolimab On February 3, 2025, Vanda Pharmaceuticals and AnaptysBio announced a global exclusive licensing agreement for imsidolimab, an IL-36R antagonist monoclonal antibody. Imsidolimab has completed two pivotal global Phase III clinical trials for generalized pustular psoriasis (GPP) - GEMINI-1 and GEMINI-2, demonstrating good safety and efficacy. This drug balances the inflammatory response by inhibiting the function of the IL-36 receptor, which is particularly important for GPP patients caused by mutations in the IL36RN gene. Under the terms of the agreement, Vanda will pay AnaptysBio a $10 million upfront payment and $5 million for existing drug supplies. Additionally, AnaptysBio will be eligible for up to $35 million in future regulatory approval and sales milestone payments, as well as a 10% royalty on global net sales. In this transaction, Vanda has obtained the global exclusive rights to develop, produce, and commercialize imsidolimab. These funds will support further research and development efforts to ensure that imsidolimab can reach the market as soon as possible. In the Phase III clinical trial of GEMINI-1, 53% of patients receiving a 750 mg intravenous injection of imsidolimab achieved a GPP Physician's Global Assessment (GPPPGA) score of 0/1 (skin almost or completely clear) at week 4, compared to only 13% in the placebo group (p=0.0131). In the subsequent GEMINI-2 trial, all patients in the maintenance dose treatment group maintained a GPPPGA score of 0/1 without relapse, while 63% of patients in the placebo group experienced disease worsening. These results indicate that imsidolimab has significant efficacy for GPP. Summary The clinical-stage drug investment, financing, and collaboration transactions in February 2025 revealed several trends: First, capital continues to be optimistic about innovative drugs, especially those with breakthrough therapeutic potential, and is willing to invest substantial funds to support research and development. Second, antibody-drug conjugates (ADCs) have become one of the key areas of collaboration, demonstrating the global popularity of this technology platform. Lastly, Chinese pharmaceutical companies are not only seeking growth opportunities in the domestic market but also actively expanding into international markets, accelerating the global layout and commercialization of new drugs through licensing deals and other means. These dynamics indicate that, despite the many challenges facing the pharmaceutical industry, companies are actively exploring new development paths through capital injection and technological collaboration, aiming to gain a favorable position in global competition. How to get the latest progress on drug deals? If you would like to access the latest transaction event information, you can click on the 'Deal' module from the homepage of the Synapse database. Within the Deal module, you can search for global pharmaceutical transaction information using labels such as Drugs, Organization, Target, Drug Type, Deal Date.  Furthermore, you can obtain the original link to the transaction coverage by clicking on the "Deal Name." In the analysis view, you can see the most active assignors, assignees, popular targets, and other dimensions of analysis, as well as the distribution of research and development statuses at the time of the transaction, to help you better understand the search results. The Synapse database also supports the ability to view current transactions from the dimension of "drugs" (by selecting "drugs" from the "Adjust Dimension" dropdown menu above). Targeting transactions involving renowned pharmaceutical companies that are of interest to the industry, such as Merck, Roche, etc., Synapse has identified a group of "leading companies" through drugs that have achieved global sales exceeding 1 billion US dollars in 2022. Transactions involving drugs from these leading companies can be filtered by clicking on the "Leading Company" tag on the left-hand side. In addition to the drug transaction module, you can also view related transaction history on the drug detail page and the institution detail page. Click on the image below to explore new pharmaceutical funding transactions!