MELAS Syndrome

Jan. 27, 2025 -- Tisento Therapeutics today announced that the first patient has been dosed in its global Phase 2b PRIZM study. The study is investigating the impact of once-daily oral zagociguat treatment on fatigue, cognitive impairment, and other key aspects of the rare mitochondrial disease MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes). The PRIZM study is centered in multiple ways on what matters to people living with MELAS. The study incorporates features that maximize convenience for participants, including at-home assessments, the potential for at-home study visits, and door-to-door travel support. In addition, all participants will receive zagociguat during one period of this crossover study, and participants who complete the study may be eligible for continued access via an open-label extension study. Importantly, the clinical outcome assessments and endpoint strategy for the PRIZM study were informed by Tisento’s interview study in which individuals living with MELAS described the symptoms and impacts of the disease that are most important to them. PRIZM is a global study now enrolling in North America, Europe, and Australia. Patients and families interested in learning more can visit Tisento’s PRIZM page, ClinicalTrials.gov (NCT06402123), or discuss with their physician. “Since Tisento’s founding, we have been focused on initiating a thoughtful, well-designed clinical study to evaluate zagociguat for the treatment of MELAS, and we are humbled by the enthusiastic response we have received from physicians and the mitochondrial disease community,” said Peter Hecht, PhD, chief executive officer of Tisento. “We are pleased that the first participants are enrolling in the global PRIZM study, which was designed with patient perspectives at the forefront. We will continue to put patients first every step of the way as we work to develop creative solutions to address what matters most for people with serious diseases.” “MELAS is the most common condition we see in our mitochondrial clinic, with profound effects on patients' daily lives and wellbeing. Right now, we have no approved treatments, making the search for effective therapies absolutely critical,” said Dr. Austin Larson, associate professor of pediatric clinical genetics and metabolism at the University of Colorado School of Medicine and PRIZM study investigator. “I am excited about zagociguat's potential to address both the severe fatigue and cognitive challenges that so significantly impact our MELAS patients.” PRIZM – a Phase 2b Randomized, Placebo-Controlled Trial Investigating Zagociguat in MELAS – is evaluating the efficacy and safety of oral zagociguat 15 mg or 30 mg compared to placebo when administered once-daily for 12 weeks in participants with genetically and phenotypically defined MELAS. The PRIZM study has a crossover design, with two 12-week treatment periods separated by a 4-week washout period. All participants will receive zagociguat during one of the 12-week periods and placebo during the other. Participants who complete the study may be eligible for an open-label extension study. PRIZM is a global study that will enroll approximately 44 participants at mitochondrial disease centers of excellence in the U.S., Italy, Germany, United Kingdom, Australia, and Canada. For more information, please visit www.tisentotx.com/prizm or ClinicalTrials.gov (NCT06402123) for more information. Interested individuals can also reach out to their physicians for participation details. Zagociguat is a once-daily, oral, clinical-stage investigational medicine with potential to positively impact both peripheral and central nervous system manifestations of mitochondrial diseases. Zagociguat stimulates soluble guanylate cyclase (sGC), an enzyme that is found in virtually every cell in every tissue of the body and is part of a system of cellular mechanisms that control critical physiological functions including neuronal function and blood flow. A first-in-class, brain-penetrant sGC stimulator, zagociguat is hypothesized to rebalance dysregulated cellular pathways in MELAS. By restoring cellular functions that support mitochondria, zagociguat may help restore mitochondrial energy production and physiological function. In a Phase 2a study in patients with MELAS, zagociguat exhibited a favorable safety profile, exposure throughout the body including in the central nervous system, and improvements in neuronal function, mitochondrial function, and blood flow in the brain. Zagociguat is currently being evaluated as a treatment for MELAS in the Phase 2b PRIZM study. Tisento Therapeutics, a privately held biotech company, is developing novel medicines to treat diseases with significant unmet need, beginning with MELAS and other genetic mitochondrial diseases. Ti sento means “I hear you” in Italian; our approach to innovation begins with listening to patients and then channeling what we learn into decisive actions that shape our research and clinical programs. Tisento is guided by a high-caliber internal team of biopharma veterans and an extensive external network of expert physicians, patient advocacy groups, researchers, industry-leading vendors, and other close collaborators who are partners in our mission to develop meaningful treatments for mitochondrial diseases. The content above comes from the network. if any infringement, please contact us to modify.

Jupiter, Florida, Jan. 13, 2025 (GLOBE NEWSWIRE) -- Jupiter Neurosciences, Inc. (NASDAQ: JUNS) (“Jupiter” or the “Company”), a clinical-stage pharmaceutical company developing JOTROL™, a patented resveratrol-based platform, today announced a strategic focus on targeting the NLRP3 inflammasome in all upcoming clinical trials. This shift aims to unlock new therapeutic potential for neurodegenerative diseases, longevity, and aging, positioning the Company at the forefront of innovation in neuroinflammation treatments. The NLRP3 inflammasome is a key inflammation driver linked to central nervous system (CNS) disorders, metabolic diseases, and aging-related conditions. JOTROL, Jupiter’s flagship product, overcomes resveratrol’s historical challenges of poor bioavailability and gastrointestinal side effects. With its ability to safely reach therapeutic levels in plasma and cross the blood-brain barrier, JOTROL represents a groundbreaking advance for targeting neuroinflammatory pathways like NLRP3. “By adding focus on NLRP3 evaluation, in addition to earlier established biomarkers, we expect to maximize JOTROL’s therapeutic potential in addressing unmet medical needs,” said Christer Rosén, Chairman and CEO of Jupiter Neurosciences. “We believe JOTROL’s ability to inhibit NLRP3, based on multiple published resveratrol trials, makes it an ideal candidate for diseases such as Parkinson’s and Alzheimer’s, and it positions Jupiter to pursue additional collaborations, particularly in the rapidly growing obesity treatment market.” Advancing Parkinson’s and Alzheimer’s Research Preclinical studies at the University of Miami have demonstrated JOTROL’s ability to mitigate key biomarkers of Parkinson’s disease, making this a primary target for Jupiter’s future trials. The company also continues to refine its strategy for Alzheimer’s research, leveraging its prior Phase I pharmacokinetics study funded by the National Institute on Aging. The U.S. Senate’s recent passage of the "National Plan to End Parkinson’s Act" highlights the growing urgency for effective treatments, and Jupiter is aligning its clinical focus to capitalize on this momentum. With a $50 billion market for Alzheimer’s treatments and a $500 million opportunity in Parkinson’s, Jupiter is well-positioned to address these high-value areas. Market Expansion and Strategic Partnerships In addition to its CNS focus, Jupiter is evaluating opportunities in longevity and metabolic health. Emerging data suggests that JOTROL’s inhibition of NLRP3, when combined with GLP-1 treatments, could enhance weight loss outcomes, opening doors to potential collaborations in the obesity market—a multibillion-dollar industry. The Company is also pursuing expansion in the Asia-Pacific region, driven by strong interest from regional partners. Recent agreements to accelerate clinical development and regulatory approval underscore Jupiter’s commitment to global growth. Why JOTROL is Different JOTROL’s patented micellar delivery system allows resveratrol to reach effective concentrations in the bloodstream without causing gastrointestinal side effects—a longstanding barrier for resveratrol-based treatments. This innovative approach has been validated in peer-reviewed studies and forms the basis of Jupiter’s strategy to pursue regulatory approval across multiple indications. About Jupiter Neurosciences, Inc. Jupiter Neurosciences is a clinical-stage pharmaceutical company focused on treating neuroinflammation, with a current focus on CNS disorders and rare diseases. The Company’s platform product, JOTROL™, is an enhanced orally administered resveratrol formulation designed and intended to deliver therapeutically relevant, safe levels of resveratrol. The Company’s pipeline is focused broadly on CNS disorder and includes indications such as Alzheimer’s Disease, Parkinson’s Disease, Mucopolysaccharidoses Type I, Friedreich’s Ataxia, and MELAS. More information may be found on the Company’s website www.jupiterneurosciences.com. About JOTROL Resveratrol is one of the world’s most extensively researched molecules. Thorough evaluation has shown that for the compound to be effective, it requires a high C-Max (~300 ng/ml of resveratrol in plasma), achievable only with doses exceeding 3 grams using earlier resveratrol products. Poor bioavailability has been a well-documented issue with resveratrol. Doses over 2 grams have been associated with severe gastrointestinal (GI) side effects, which have prevented the compound from receiving regulatory approval for any indication.\ Jupiter Neurosciences (JUNS) conducted a Phase I study demonstrating that JOTROL achieves over nine times higher bioavailability compared to resveratrol used in earlier clinical trials (e.g., Turner et al., MCI/Early Alzheimer’s Disease trial, and Yui et al., Friedreich’s Ataxia trial). The results of this Phase I study, which will be cross-referenced in all upcoming JOTROL trials, were published in the Journal of Alzheimer’s Disease and AAPS Open in February 2022. About NLRP3 The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int J Mol Sci. 2019 Jul 6;20(13):3328. doi: 10.3390/ijms20133328. PMID: 31284572; PMCID: PMC6651423. FORWARD-LOOKING STATEMENTS Certain statements in this announcement are forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties and are based on the Company’s current expectations, including the use of proceeds from the Offering. Investors can find many (but not all) of these statements by the use of words such as “approximates,” “believes,” “hopes,” “expects,” “anticipates,” “estimates,” “projects,” “intends,” “plans,” “will,” “would,” “should,” “could,” “may” or other similar expressions. Although the Company believes that the expectations expressed in these forward-looking statements are reasonable, it cannot assure you that such expectations will turn out to be correct. The Company cautions investors that actual results may differ materially from the anticipated results and encourages investors to read the risk factors contained in the Company’s final prospectus and other reports it files with the SEC before making any investment decisions regarding the Company’s securities. The Company undertakes no obligation to update or revise publicly any forward-looking statements to reflect subsequent occurring events or circumstances, or changes in its expectations, except as may be required by law. Contact: Dave GentryRedChip Companies, Inc.1-407-644-42561-800-RED-CHIP (733-2447)JUNS@redchip.com

Proposed acquisition strengthens Pharming’s late-stage pipeline with a potential first-in-disease asset Abliva’s lead product KL1333 is currently in a pivotal clinical trial, with a positive interim analysis achieved, in mitochondrial DNA-driven primary mitochondrial diseases Total transaction value of approximately US$66.1 million No external funding required to fund acquisition and KL1333 development costs Pharming to host a conference call on Monday, December 16, 2024 at 14:00 CET (8:00 am EST) Leiden, the Netherlands, December 15, 2024: Pharming Group N.V. (“Pharming” or “the Company”) (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) today announced a recommended public cash offer to the shareholders of Abliva AB (“Abliva”) to acquire all issued and outstanding shares of Abliva. Pharming, through its wholly-owned subsidiary Pharming Technologies B.V., offers the shareholders SEK 0.45 in cash per share in Abliva. The transaction is valued at approximately US$66.1 million. Abliva is a biotechnology company, based in Lund, Sweden, focused on developing medicines for the treatment of mitochondrial disease. Abliva’s lead product, KL1333, a regulator of the essential co-enzymes NAD⁺ and NADH, is in a pivotal clinical study (FALCON) in adult patients with genetically confirmed primary mitochondrial disease (PMD) with mitochondrial DNA (mtDNA) mutations who experience consistent, debilitating fatigue and muscle weakness (myopathy), and reduced life expectancy. Over 30,000 patients diagnosed with mtDNA mitochondrial disease would be potentially addressable by KL1333 in the U.S., EU4 (France, Germany, Italy, Spain) and the UK. KL1333 has shown positive clinical effects in a proof-of-concept Phase 1b study, and a pre-planned interim analysis of the ongoing pivotal FALCON trial demonstrated promising differences over placebo in both alternate primary efficacy endpoints. KL1333 has received Fast Track designation in the U.S. and Orphan Drug Designation for the treatment of PMD in the U.S. and EU. Sijmen de Vries, Chief Executive Officer of Pharming, said:“Abliva has made exciting progress developing KL1333, a potential first-in-disease treatment undergoing a pivotal clinical trial that offers new hope to patients with rare mtDNA mitochondrial disease who experience debilitating fatigue and muscle weakness. With over 30,000 addressable patients in the U.S., EU4 and UK, we are excited about the potential of this asset, which achieved a positive interim analysis in the registration trial in July 2024. We believe KL1333 has blockbuster potential in the U.S. alone and can significantly change Pharming’s future growth trajectory. We will fund this acquisition using existing cash, and anticipate covering costs to complete the pivotal trial with positive cash flows from our existing business. The acquisition of Abliva would further strengthen our clinical pipeline with the addition of a therapy, with U.S. launch expected in 2028, aligning with our vision to become a leading global rare disease company. We are pleased that Abliva’s independent Board of Directors and major shareholders recognize the expertise and value Pharming brings to the development and eventual commercialization of KL1333, and unanimously support this transaction. We look forward to welcoming the Abliva team with their strong expertise in mitochondrial research and drug development and to combining with our resources, capabilities and commercial infrastructure to bring this groundbreaking and important medicine to patients and their healthcare providers.” Transaction highlightsToday at 19:45 CET, Pharming announced a recommended cash offer to the shareholders of Abliva AB. Hereby Pharming, through a wholly owned subsidiary, has offered SEK 0.45 in cash for each outstanding share of Abliva (the ''Offer''). The total value of the Offer based on all outstanding 1,611,884,536 shares in Abliva amounts to approximately SEK 725,348,041, or approximately US$66.1 million. The Board of Directors of Abliva unanimously recommends the shareholders of Abliva to accept the Offer. The Board of Directors of Abliva has obtained a fairness opinion from PwC, according to which, based on the assumptions and reservations stated in the opinion, the Offer is fair to Abliva’s shareholders from a financial perspective. Pharming has obtained acceptance undertakings from the three largest shareholders, accounting for 49.82% of Abliva's outstanding shares. The Offer is subject to customary regulatory approvals, and Pharming expects to obtain such approvals prior to the end of the acceptance period. Pharming Group N.V. has cash on hand to finance the Offer in full. The acceptance period in the offer is expected to commence on or around January 16, 2025 and to expire on or around February 7, 2025. For information in relation to the Offer, please refer to www.raredisease-offer.com. An offer document will be made public by Pharming shortly before the commencement of the acceptance period. Van Lanschot Kempen N.V. is sole financial advisor and NautaDutilh N.V. and Mannheimer Swartling Advokatbyrå are legal advisors to Pharming in connection with the Offer. Invitation to conference callPharming to host a conference call on Monday, December 16, 2024, at 14:00 CET (8:00 am EST). The conference call presentation is available on the pharming.com website from 14:00 CET on December 16, 2024 A transcript will be made available on the pharming.com website in the days following the call. To participate in the conference call, please register in advance using the link below. Once registered, dial-in information and a unique PIN will be provided, allowing access to the call. Conference call dial-in details:Please note, the Company will only take questions from dial-in attendees. https://register.vevent.com/register/BIfcd1fd2bdf0e443cbf6192dc063763ad Webcast Link: https://edge.media-server.com/mmc/p/2hfpccyi For further public information, contact:Pharming Group, Leiden, the NetherlandsMichael Levitan, VP Investor Relations & Corporate CommunicationsT: +1 (908) 705 1696E: investor@pharming.com FTI Consulting, London, UKVictoria Foster Mitchell/Alex Shaw/Amy ByrneT: +44 203 727 1000 LifeSpring Life Sciences Communication, Amsterdam, the NetherlandsLeon MelensT: +31 6 53 81 64 27E: pharming@lifespring.nl Abliva investorsLeo Wei T: +46 (0)709 910 081E: pharming@fogelpartners.se About KL1333KL1333 has been designed to treat chronic fatigue and myopathy (muscle weakness) in genetically confirmed adult patients with primary mitochondrial disease. Diagnoses can include MELAS-MIDD and KSS-CPEO spectrum disorders as well as MERRF syndrome. The drug candidate is intended for long-term oral treatment. KL1333 has the ability to restore the ratio of NAD+ and NADH, and thus leads to the formation of new mitochondria and improved energy levels. In a cohort of mitochondrial disease patients in a Phase 1a/b study, the patients who received KL1333 showed both improvements in symptoms of fatigue as well as functional improvements. KL1333 is currently being evaluated in a global, potentially registrational, Phase 2 study (the FALCON study) and has received orphan drug designation in both the USA and Europe as well as Fast Track designation in the USA. About the FALCON StudyFALCON is a Phase 2, global, randomized, placebo-controlled, potentially registrational study evaluating the safety and efficacy of KL1333 in adult patients with primary mitochondrial disease who experience consistent, debilitating fatigue and myopathy (muscle weakness), the most common and impairing symptoms. A total of 180 patients with mitochondrial DNA mutations who meet the eligibility criteria are randomized 3:2 to receive KL1333 (50mg-100mg) or placebo twice daily for 48 weeks. The two alternative primary endpoints assess consistent fatigue (using the PROMIS® Fatigue Mitochondrial Disease Short Form) and myopathy (using the 30 second Sit-to-Stand test), only one of which must be positive to file for marketing approval. An interim analysis evaluating 24-week data from the first wave of patients confirmed the strong safety profile of KL1333, and both primary endpoints passed futility, meaning that both have the potential to demonstrate benefit in the final analysis of the study. About Abliva ABAbliva discovers and develops medicines for the treatment of mitochondrial disease. This rare and often very severe disease occurs when the cell’s energy provider, the mitochondria, do not function properly. The company has prioritized two projects. KL1333, a powerful regulator of the essential co-enzymes NAD⁺ and NADH, has entered late-stage development. NV354, an energy replacement therapy, has completed preclinical development. Abliva, based in Lund, Sweden, is listed on Nasdaq Stockholm, Sweden (ticker: ABLI). For more information, please visit www.abliva.com. About Pharming Group N.V. Pharming Group N.V. (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) is a global biopharmaceutical company dedicated to transforming the lives of patients with rare, debilitating, and life-threatening diseases. Pharming is commercializing and developing an innovative portfolio of protein replacement therapies and precision medicines, including small molecules and biologics. Pharming is headquartered in Leiden, the Netherlands, and has employees around the globe who serve patients in over 30 markets in North America, Europe, the Middle East, Africa, and Asia-Pacific. For more information, visit www.pharming.com and find us on LinkedIn. Forward-Looking Statements   This press release may contain forward-looking statements. Forward-looking statements are statements of future expectations that are based on management’s current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. These forward-looking statements are identified by their use of terms and phrases such as “aim”, “ambition”, ‘‘anticipate’’, ‘‘believe’’, ‘‘could’’, ‘‘estimate’’, ‘‘expect’’, ‘‘goals’’, ‘‘intend’’, ‘‘may’’, “milestones”, ‘‘objectives’’, ‘‘outlook’’, ‘‘plan’’, ‘‘probably’’, ‘‘project’’, ‘‘risks’’, “schedule”, ‘‘seek’’, ‘‘should’’, ‘‘target’’, ‘‘will’’ and similar terms and phrases. Examples of forward-looking statements may include statements with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory, commercial, competitive and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2023 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. All forward-looking statements contained in this press release are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. Readers should not place undue reliance on forward-looking statements. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release. Pharming does not undertake any obligation to publicly update or revise any forward-looking statement as a result of new information, future events or other information. Inside Information  This press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation. Attachment Pharming announces public cash offer to the shareholders of Abliva AB_EN_15DEC24