Core Insights - The FDA has granted Fast Track designation to QTORIN™ rapamycin for the treatment of angiokeratomas, highlighting its potential to address a significant unmet medical need [1][2][3] - Palvella Therapeutics plans to initiate a Phase 2 trial for QTORIN™ rapamycin in the second half of 2026, following discussions with the FDA [1][4] Company Overview - Palvella Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for serious, rare skin diseases without FDA-approved treatments [5] - The company is developing a pipeline of product candidates based on its QTORIN™ platform, with QTORIN™ rapamycin as the lead candidate targeting microcystic lymphatic malformations, cutaneous venous malformations, and clinically significant angiokeratomas [5] Industry Context - Angiokeratomas are chronic skin lesions with no FDA-approved therapies, affecting an estimated 50,000 diagnosed patients in the U.S. [1][2] - The FDA's Fast Track program aims to expedite the development and review of drugs for serious conditions, facilitating earlier access for patients [3]

Core Insights - The FDA has granted Fast Track designation to QTORIN™ rapamycin for the treatment of angiokeratomas, highlighting its potential to address a significant unmet medical need [1][2][3] - Palvella Therapeutics plans to initiate a Phase 2 trial for QTORIN™ rapamycin in the second half of 2026, following discussions with the FDA [1][4] Company Overview - Palvella Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for serious, rare skin diseases without FDA-approved treatments [5] - The company is developing a pipeline of product candidates based on its QTORIN™ platform, with QTORIN™ rapamycin as the lead candidate targeting microcystic lymphatic malformations, cutaneous venous malformations, and clinically significant angiokeratomas [5][6] Industry Context - Angiokeratomas are chronic skin lesions with no FDA-approved therapies, affecting an estimated 50,000 diagnosed patients in the U.S. [1][2] - The FDA's Fast Track program aims to expedite the development and review of drugs for serious conditions, facilitating earlier access for patients [3]

Registration No. 333-291598 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 AMENDMENT NO. 1 TO FORM F-1 As filed with the U.S. Securities and Exchange Commission on December 8, 2025. REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Biodexa Pharmaceuticals PLC (Exact name of registrant as specified in its charter) (State or Other Jurisdiction of Incorporation or Organization) England and Wales 2834 Not Applicable (Primary Standard Industrial Classification Code Number) (IRS Emp ...

Core Insights - MediciNova, Inc. has provided an update on its Phase 2b/3 clinical trial of MN-166 (ibudilast) for Amyotrophic Lateral Sclerosis (ALS), known as the COMBAT-ALS study, with results presented at the 36th International Symposium on ALS/MND [1][2] Company Overview - MediciNova, Inc. is a clinical-stage biopharmaceutical company focused on developing novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases, with a late-stage pipeline including MN-166 (ibudilast) and MN-001 (tipelukast) [4][6] Clinical Trial Update - The COMBAT-ALS trial has successfully randomized a total of 234 participants, completing enrollment in September 2025 [5] - The baseline characteristics of participants include a mean age of 60.6 years, with 36.8% female and 63.2% male, and a racial distribution predominantly Caucasian (90.2%) [5] - The mean ALSFRS-R score at screening was 40.6, indicating the severity of the disease among participants [5] Drug Development and Designation - MN-166 (ibudilast) has received Orphan Drug Designation and Fast Track Designation from the FDA, as well as Orphan Designation from the European Commission for ALS treatment [3][2] - The drug is also in late-stage development for other neurodegenerative diseases and conditions, including progressive multiple sclerosis and glioblastoma [3][4] Future Expectations - Top-line data from the COMBAT-ALS study is anticipated by the end of 2026, with the company expressing hope that MN-166 will provide a significant therapeutic advance for ALS patients [2]

Core Insights - The FDA has granted Fast Track designation to CLN-049 for treating relapsed/refractory acute myeloid leukemia (AML), highlighting the urgent need for new treatment options in this area [1][2] - Initial results from the Phase 1 study of CLN-049 indicate meaningful efficacy, including complete responses, suggesting its potential as a novel immunotherapeutic approach for AML [2][4] - CLN-049 is a bispecific T cell engager designed to target FLT3-expressing leukemia cells, making it applicable to a broad population of AML patients regardless of FLT3 mutational status [4][5] Company Overview - Cullinan Therapeutics, Inc. is focused on developing first- or best-in-class therapies for autoimmune diseases and cancer, leveraging expertise in T cell engagers [8] - The company is advancing its clinical-stage pipeline with a rigorous scientific approach aimed at delivering new standards of care for patients [8] Industry Context - Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with approximately 22,000 new diagnoses annually in the U.S. and around 11,000 deaths [6] - Despite recent advances, the five-year survival rate for patients with relapsed or refractory AML is 10% or less, indicating a significant unmet medical need for effective therapies [7] - Currently, there are no approved immunotherapies for AML, underscoring the critical demand for innovative treatment options [7]

Core Insights - Can-Fite BioPharma Ltd. announced a patient treated with Namodenoson has achieved an overall survival of 9 years with a complete response to treatment [1][2] Company Overview - Can-Fite BioPharma Ltd. is a biotechnology company focused on developing proprietary small molecule drugs for oncological and inflammatory diseases [1][7] - The company is advancing its lead drug candidate, Namodenoson, which is currently in a pivotal Phase III clinical study for advanced hepatocellular carcinoma (HCC) [3][7] Clinical Development - Namodenoson has shown promising results in a completed Phase II study, with a patient remaining cancer-free for 9 years [2][4] - The drug is being evaluated in multiple clinical trials, including a Phase IIb trial for Metabolic Dysfunction-associated Steatohepatitis (MASH) and a Phase IIa study in pancreatic cancer [6][7] - The U.S. FDA and European Medicines Agency have granted Namodenoson Orphan Drug status and Fast Track status for HCC treatment [3][7] Market Potential - The global market for HCC treatments is projected to reach $6.1 billion by 2027 for the G8 countries, driven by the need for effective and safe treatment options [5] - Liver cancer accounts for over 700,000 deaths globally each year, highlighting the urgent need for new therapies [5] Drug Mechanism - Namodenoson is a small orally bioavailable drug that selectively binds to the A3 adenosine receptor (A3AR), which is highly expressed in diseased cells, contributing to its excellent safety profile [6]

Core Insights - NRx Pharmaceuticals has made significant progress in advancing its corporate objectives and has entered revenue-generating activities for the first time in 2025 [2] - The company is focusing on two main products: NRX-100 for suicidal depression and NRX-101 for bipolar depression, with both products receiving regulatory designations to expedite their development [3][4] Financial Performance - For the quarter ended September 30, 2025, NRx Pharmaceuticals reported a loss from operations of $4.0 million, an increase from a loss of $3.0 million in the same quarter of 2024, primarily due to increased research and development expenses [14] - The company reported revenue of approximately $240,000 for the first time, driven by the acquisition of Dura Medical, which closed on September 8, 2025 [14] - As of September 30, 2025, the company had approximately $7.1 million in cash and cash equivalents, which would increase to $10.3 million after accounting for a subscription receivable [14][16] Product Development and Regulatory Updates - NRX-100 is being developed through both an NDA under FDA Fast Track designation and an ANDA for a preservative-free ketamine product, with the generic ketamine market estimated at approximately $750 million [3][6] - The NDA for NRX-100 is expected to be completed in Q4 2025, incorporating Real World Efficacy Data from over 60,000 patients [4] - NRX-101 has shown promising Real World Efficacy data, indicating that it can double the antidepressant and anti-suicidal effects of Transcranial Magnetic Stimulation (TMS) [10] Corporate Strategy and Expansion - HOPE Therapeutics, a subsidiary of NRx Pharmaceuticals, is expanding its network of interventional psychiatry clinics, with three facilities currently operational in Florida and plans for more by year-end [6][12] - The company is actively pursuing additional acquisitions to enhance its clinic network, with potential revenue from these acquisitions estimated to exceed $20 million annually [15] - NRx Pharmaceuticals is also working on a nationwide expanded access program for NRX-101, allowing physicians to provide the medication at no charge to patients [10]

Core Insights - BioRestorative Therapies, Inc. has received a Type B meeting with the FDA to discuss an accelerated Biologics License Application pathway for its BRTX-100 program targeting chronic lumbar disc disease [1][2] - The company aims to present positive safety and efficacy data from its ongoing Phase 2 clinical trial during the FDA meeting and seeks an expedited timeline for a Phase 3 trial [2] Company Overview - BioRestorative is focused on regenerative medicine, particularly stem cell-based therapies, and has two main clinical development programs: the Disc/Spine Program and the Metabolic Program [6][8] - BRTX-100 is the lead candidate in the Disc/Spine Program, designed to treat chronic lumbar disc disease through a cell-based therapeutic approach [5][6] - The company also operates a BioCosmeceutical platform, developing products aimed at cosmetic applications using cell-based technologies [9] Clinical Development - The BRTX-100 Phase 2 clinical trial has been granted Fast Track designation by the FDA, facilitating its development and review process [3] - The trial involves up to 99 subjects across 16 clinical sites in the U.S., with a randomized 2:1 allocation to BRTX-100 or placebo [5] - Chronic lumbar disc disease affects a significant portion of the adult population, with at least 80% experiencing lower back pain at some point in their lives [4] Market Context - Chronic lumbar disc disease is a major cause of disability and economic burden in the U.S., with current treatments focusing on symptomatic relief rather than reversing disc degeneration [4] - The FDA's Fast Track designation for BRTX-100 indicates its potential to address significant unmet medical needs in this area [3]

Core Insights - Altimmune, Inc. is approaching significant milestones in the development of pemvidutide for metabolic dysfunction-associated steatohepatitis (MASH) and alcohol use disorder (AUD) [2][12] - The company has strengthened its executive leadership team with key appointments to support its growth strategy [2][9] - Financial results indicate a robust cash position and a reduction in research and development expenses compared to the previous year [7][19] MASH Program Updates - The 48-week data from the Phase 2b IMPACT trial of pemvidutide is expected to be released before the end of 2025 [2][12] - An End-of-Phase 2 meeting with the FDA is scheduled for the fourth quarter of 2025 to discuss the proposed design of the Phase 3 trial [5][12] - The trial design may include flexibility to adapt based on regulatory discussions regarding non-invasive tests and AI-based biopsy readings [2] AUD and ALD Trials - The RECLAIM trial for pemvidutide in AUD has completed patient recruitment ahead of schedule, indicating strong interest in new therapies for this condition [9][12] - The RESTORE trial for pemvidutide in alcohol-associated liver disease (ALD) has also been initiated, with a focus on safety and efficacy [9][12] Executive Leadership Changes - Recent appointments include Dr. Christophe Arbet-Engels as Chief Medical Officer, Linda Richardson as Chief Commercial Officer, and Robin Abrams as Chief Legal Officer [2][9] - These leaders bring extensive experience in clinical development, commercial strategy, and legal compliance to the company [9] Financial Performance - As of September 30, 2025, the company reported cash, cash equivalents, and short-term investments totaling approximately $211 million, a 60% increase from $131.9 million at the end of 2024 [7][19] - Research and development expenses decreased to $15 million from $19.8 million year-over-year, reflecting a strategic focus on cost management [19] - The net loss for the quarter was $19 million, or $0.21 per share, an improvement from a net loss of $22.8 million, or $0.32 per share, in the same period in 2024 [19]

Core Insights - Esperion Therapeutics (ESPR) has nominated ESP-2001, a specific allosteric ATP citrate lyase (ACLY) inhibitor, as a new preclinical development candidate for treating primary sclerosing cholangitis (PSC), a rare autoimmune liver disease with no approved treatments [1][7] - The company plans to initiate IND-enabling studies for ESP-2001 and submit an IND application to the FDA, aiming to start clinical studies in 2026 [2] - ESP-2001 has shown potential in reducing liver and bile duct injury, inflammation, and fibrosis in preclinical studies, indicating its ability to impact PSC progression [3] Company Developments - Esperion's stock rose by 5.2% following the announcement of ESP-2001 [2] - The collaboration with Evotec (EVO) was crucial in discovering ESP-2001, combining Esperion's expertise in ACLY therapy with Evotec's drug discovery platform [2][3] - The nomination of ESP-2001 triggered an undisclosed payment to Evotec [3] Financial Performance - Esperion's net product sales of Nexletol and Nexlizet in the U.S. grew by 42% in the first half of 2025, reaching $75.2 million, driven by increased prescription volumes [10] - Esperion aims to diversify its portfolio beyond cardiovascular diseases into the liver disorder market, targeting a potential market opportunity exceeding $1 billion annually with ESP-2001 [10] Market Position - Esperion currently holds a Zacks Rank of 3 (Hold) [11] - The company has two FDA-approved drugs, Nexletol and Nexlizet, which are marketed under different names in ex-U.S. markets [8][9]