Committee for Medicinal Products for Human Use (CHMP) issues a positive opinion following re-examination, which will be reviewed by the European Commission (EC), with a decision anticipated by March 2026 If approved by the EC, this dosing regimen would reduce the burden to eligible adult patients, their families and the broader healthcare system due to the current requirement to visit infusion centres or have home infusions every-2-weeks for treatment PARMA, Italy and CARMIEL, Israel, Jan. 30, 2026 (GLOBE N ...

Core Insights - Denali Therapeutics Inc. announced the publication of results from the Phase 1/2 clinical trial of tividenofusp alfa for Hunter syndrome, with FDA Priority Review for its Biologics License Application expected by April 5, 2026 [1][5] Company Overview - Denali Therapeutics is focused on developing biotherapeutics that can cross the blood-brain barrier using its proprietary TransportVehicle™ platform [13] - The company is advancing a portfolio of therapeutic candidates aimed at treating neurodegenerative and lysosomal storage diseases [13] Clinical Trial Results - The Phase 1/2 trial involved 47 participants, showing that tividenofusp alfa significantly reduced central nervous system and peripheral biomarkers of substrate accumulation and neuronal injury [3][6] - Key findings included a 91% reduction in cerebrospinal fluid levels of heparan sulfate and an 88% reduction in urine levels at Week 24, with normalization of liver volume and improvements in hearing and cognitive skills [11][5] Treatment Mechanism - Tividenofusp alfa is designed to deliver the iduronate 2-sulfatase enzyme to the brain and body, addressing both neurological and physical symptoms of Hunter syndrome [4][7] - The treatment has received multiple designations from the FDA, including Rare Pediatric Disease Designation and Breakthrough Therapy Designation [7] Future Developments - Denali is conducting the Phase 2/3 COMPASS study to support global approval, comparing tividenofusp alfa with standard treatment idursulfase [8] - The company is also exploring the potential of its TransportVehicle platform for delivering other therapeutic agents, including antibodies and oligonucleotides [12]

Core Insights - Denali Therapeutics Inc. (DNLI) has secured a funding agreement with Royalty Pharma plc (RPRX) amounting to $275 million, leading to a 5.84% increase in stock price following the announcement [1][7] - The funding is linked to the future net sales of Denali's lead drug candidate, tividenofusp alfa, which is aimed at treating mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome [1][7] Funding Agreement Details - The agreement provides a significant capital influx as Denali approaches a critical regulatory event, with the biologics license application (BLA) for tividenofusp alfa under review in the U.S., targeting an action date of April 5, 2026 [2][8] - The deal includes an initial payment of $200 million upon closing, with an additional $75 million contingent on obtaining European Medicines Agency approval by December 31, 2029 [4][5] Royalty Structure - Royalty Pharma will receive a 9.25% royalty on worldwide net sales of tividenofusp alfa, with payments ceasing upon reaching a multiple of 3.0x, or 2.5x if achieved by the first quarter of 2039 [5] Regulatory Timeline - The FDA extended the review timeline for the BLA from January 5, 2026, to April 5, 2026, due to a major amendment submission by Denali, which was not related to efficacy, safety, or biomarkers [8][9] - The FDA has previously granted multiple designations to tividenofusp alfa, including Breakthrough Therapy and Fast Track [9] Financial Position - As of September 30, 2025, Denali reported cash, cash equivalents, and marketable securities totaling approximately $872.9 million [10] Other Development Candidates - Denali is also developing other candidates in collaboration with Takeda and Biogen, including DNL593 for frontotemporal dementia and BIIB122 for early-stage Parkinson's disease [11][12]

Core Insights - Denali Therapeutics (DNLI) reported a narrower loss of 74 cents per share for Q3 2025, compared to the Zacks Consensus Estimate of a loss of 76 cents and a loss of 63 cents in the same quarter last year [1][8] - The company did not generate any collaboration revenues in the reported quarter, missing the Zacks Consensus Estimate of $14 million [2] - DNLI's stock has declined by 29.3% year-to-date, while the industry has grown by 11.5% [2] Financial Performance - Research and development expenses increased by 3.8% to $101.9 million, primarily due to the start of operations at Denali's large molecule manufacturing facility in Salt Lake City, UT [4] - General and administrative expenses rose by 42.2% to $35.5 million, driven by preparations for a potential launch of tividenofusp alfa [4] - As of September 30, 2025, the company had cash, cash equivalents, and marketable securities totaling approximately $872.9 million [5] Regulatory and Pipeline Updates - The FDA extended the review timeline for the biologics license application (BLA) for tividenofusp alfa to April 5, 2026, from January 5, 2026, following the submission of updated clinical pharmacology information [6][9] - The extension was classified as a major amendment, but the FDA did not request additional data [9] - Denali is advancing programs for Sanfilippo syndrome, Alzheimer’s disease, Parkinson’s disease, and Pompe disease [8][10] Pipeline Developments - Denali is evaluating DNL126 for Sanfilippo syndrome type A, with a phase I/II study completed [10][11] - The company is also developing DNL593 in collaboration with Takeda for frontotemporal dementia and has submitted a clinical trial application for DNL628 for Alzheimer's disease [12][14] - Denali and Biogen are co-developing BIIB122, with a phase IIb study fully enrolled and results expected in 2026 [13] Overall Assessment - The delay in the approval of tividenofusp alfa is disappointing, as it is the lead candidate in Denali's pipeline, but progress with DNL126 is encouraging [15] - The company's strong cash position is a positive factor for funding ongoing programs [15]

Core Viewpoint - Chiesi Global Rare Diseases and Protalix BioTherapeutics have requested a re-examination of the negative opinion from the CHMP regarding the proposed dosing regimen for Elfabrio® (pegunigalsidase alfa) [1][2] Company Overview - Chiesi Global Rare Diseases is a business unit of the Chiesi Group, focused on delivering innovative therapies for rare diseases [16] - Protalix BioTherapeutics specializes in developing recombinant therapeutic proteins using its proprietary plant cell-based expression system, ProCellEx [18] Product Information - Elfabrio® is indicated for the treatment of adults with confirmed Fabry disease [3] - The current approved dosing regimen is 1 mg/kg every 2 weeks, while a new regimen of 2 mg/kg every 4 weeks is under review [2] Clinical Trial Insights - In clinical trials, 14% of patients treated with Elfabrio experienced hypersensitivity reactions, with 3% experiencing anaphylaxis [6] - Infusion-associated reactions were reported in 29% of patients, including symptoms such as nausea, chills, and rash [7][9] Regulatory Context - The existing marketing authorization for Elfabrio remains effective while the re-examination process is ongoing [2] - The outcome of the re-examination will influence the final decision by the European Commission [2] Disease Background - Fabry disease is a rare inherited lysosomal storage disorder caused by mutations in the GLA gene, leading to enzyme deficiency and accumulation of globotriaosylceramide (GL-3) [11][12] - Symptoms include fatigue, chronic pain, and increased risk of serious complications such as kidney failure and stroke [11][12]

Core Insights - Chiesi Global Rare Diseases and Protalix BioTherapeutics received a negative opinion from the CHMP of the EMA regarding the approval of a new dosing regimen for Elfabrio (pegunigalsidase alfa) [1][2] - The proposed regimen of 2 mg/kg every 4 weeks was not deemed to have sufficient efficacy compared to the currently approved regimen of 1 mg/kg every 2 weeks [1][2] Company Overview - Chiesi Global Rare Diseases is a unit of the Chiesi Group focused on innovative therapies for rare diseases [1][16] - Protalix BioTherapeutics specializes in developing recombinant therapeutic proteins using its proprietary ProCellEx® plant cell-based expression system [1][19] - Both companies are committed to reducing the treatment burden for patients with Fabry disease [2][20] Clinical Trial Insights - The CHMP review was based on data from the BRIGHT trial and its extension study, which had a median exposure of almost six years [2] - The data from these studies, along with modeling and exposure-response analyses from prior trials, were insufficient to demonstrate similar efficacy for the new dosing regimen [2] Fabry Disease Context - Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, leading to serious health complications [11][12] - Early detection and access to treatment are critical for managing symptoms and slowing disease progression [12] Safety Information - Elfabrio is indicated for adults with confirmed Fabry disease and has been associated with hypersensitivity reactions, including anaphylaxis [3][4] - In clinical trials, 14% of patients experienced hypersensitivity reactions, with 3% experiencing anaphylaxis [6][9]

Core Insights - Denali Therapeutics Inc. announced that the FDA has accepted the Biologics License Application (BLA) for tividenofusp alfa, seeking accelerated approval for the treatment of Hunter syndrome, with a target action date of January 5, 2026 [1][7]. Company Overview - Denali Therapeutics is a biotechnology company focused on developing therapies that can cross the blood-brain barrier (BBB) for neurodegenerative and lysosomal storage diseases [9]. - The company utilizes a proprietary TransportVehicle™ platform designed to deliver large therapeutic molecules across the BBB, enhancing drug efficacy [8]. Product Details - Tividenofusp alfa is an investigational enzyme replacement therapy designed to address both neurological and physical symptoms of Hunter syndrome by delivering the iduronate 2-sulfatase (IDS) enzyme into the brain and body [2][4]. - The therapy has received Fast Track and Breakthrough Therapy designations from the FDA, as well as Priority Medicines designation from the European Medicines Agency [4]. Clinical Studies - The BLA submission is supported by data from a Phase 1/2 study involving 47 participants with Hunter syndrome [3]. - Denali is conducting an ongoing Phase 2/3 COMPASS study to support global regulatory approvals, with participants randomized to receive either tividenofusp alfa or idursulfase [5]. Disease Context - Hunter syndrome (MPS II) is a rare genetic disorder caused by a deficiency in the IDS enzyme, leading to the accumulation of glycosaminoglycans and resulting in cognitive decline, behavioral issues, and physical complications [6]. - Current therapies do not effectively address neurological symptoms due to their inability to cross the BBB, highlighting the unmet need for new treatments [6].

Core Viewpoint - BioMarin Pharmaceutical Inc. has announced the acquisition of Inozyme Pharma, Inc. for $4.00 per share, totaling approximately $270 million, which is expected to enhance BioMarin's enzyme therapies portfolio and provide a potential first-in-class treatment for ENPP1 Deficiency [1][2][3] Acquisition Details - The acquisition is an all-cash transaction, unanimously approved by both companies' Boards of Directors, and is anticipated to close in Q3 2025, pending regulatory approval and other customary conditions [1][7][8] - BioMarin will commence a cash tender offer for all outstanding shares of Inozyme common stock at a price of $4.00 per share, with Inozyme's Board recommending that stockholders tender their shares [7][8] Product Information - INZ-701, the late-stage enzyme replacement therapy being developed for ENPP1 Deficiency, is expected to have pivotal data readout in early 2026, with potential regulatory approval in 2027 [2][4] - ENPP1 Deficiency is a rare genetic condition that leads to serious health complications, including increased cardiovascular mortality risk and severe rickets [6] Clinical Development - INZ-701 is being developed for patients of all ages, with ongoing studies for infants and plans for supportive studies for adolescents and adults [4][5] - A Phase 1/2 study in adults showed a favorable safety profile for INZ-701, with improvements in key health indicators [5] Financial Guidance - BioMarin reaffirmed its full-year 2025 financial guidance and plans to achieve a 40% Non-GAAP Operating Margin in 2026, excluding the impact of the acquisition [9]