Latest news with #FragileX
Associated Press
15-05-2025
- Business
- Associated Press
QurAlis Announces Exclusive License on Novel Mechanism for Fragile X Syndrome (FXS) to Enable Development of First Potential Disease-Modifying Therapy
CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 15, 2025-- QurAlis Corporation ('QurAlis'), a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of neurodegenerative and neurological diseases, today announced it has entered into an exclusive license agreement with UMass Chan Medical School ('UMass Chan') on a novel RNA-targeted mechanism confirmed to restore functional protein for Fragile X syndrome (FXS). Fragile X syndrome is the leading inherited form of intellectual disability and the most common single genetic cause of autism. It is a genetic condition caused by a mutation of a single gene – Fragile X messenger ribonucleoprotein 1 (FMR1) – on the X chromosome. This mutation of FMR1 causes a range of developmental problems including learning disabilities, behavioral challenges, and cognitive impairment. QurAlis' exclusive license agreement is a result of its 2024 partnership and collaboration with UMass Chan to explore the biology of FXS to determine and confirm relevant targets that could enable antisense oligonucleotide (ASO)-mediated correction for FXS. QurAlis leveraged its deep understanding, knowledge and expertise in developing ASOs as part of the collaboration. QurAlis confirmed the findings from the original publication of the UMass Chan researchers and is advancing FMR1 as a precision medicine target in up to 80 percent of FXS patients. The mis-spliced form of FMR1, designated as FMR1-217, is widely expressed throughout cortical brain areas affected in FXS and can be measured in blood and cerebrospinal fluid. Preliminary data suggest biomarker feasibility to detect mis-splicing of FMR1 in patients with FXS. 'FXS is a devastating neurodevelopmental disorder with no effective disease-modifying therapies available. Our initial partnership with UMass Chan confirmed that FMR1-217 is a validated genetic target for FXS,' said Kasper Roet, Ph.D., chief executive officer and co-founder of QurAlis. 'This groundbreaking discovery of a novel RNA-targeted mechanism to restore functional protein for FXS and the feasibility of a biomarker to detect mis-splicing of FMR1 in FXS patients opens up a completely new type of therapeutic approach through splice correction. We look forward to applying QurAlis' FlexASO® platform and deep knowledge and expertise of ASO splicing targets toward having a candidate nominated for IND-enabling studies in the near future, so that we can bring a potential new precision medicine option to patients.' Joel Richter, Ph.D., the Arthur F. Koskinas Chair in Neuroscience and professor of molecular medicine at UMass Chan, and colleagues Sneha Shah, Ph.D., and Jonathan K. Watts, Ph.D., together with Elizabeth Berry-Kravis, M.D., Ph.D., at Rush University Medical Center, have shown that aberrant alternative splicing, or mis-splicing, of messenger RNA (mRNA) plays a fundamental role in FXS. In a seminal publication by the group, it was revealed that in FXS patients, FMR1 mRNA is still being expressed, but is mis-spliced, comprising a short, truncated alternative mRNA variant called FMR1-217 which results in non-functional FMRP protein expression. Working with patient-derived cells, Dr. Richter's lab and Dr. Berry-Kravis initially demonstrated that ASOs can successfully inhibit the mis-splicing, reduce expression of FMR1-217, rescue proper FMR1 mRNA, and restore FMRP protein expression. 'This is a meaningful step in the process of taking basic biological discoveries and turning them into practical therapies that can benefit patients in the clinic,' said Dr. Richter. 'QurAlis' platform and expertise in neurodegenerative disorders are industry leading and well positioned to address the mis-splicing of FMR1 RNA and restore functional FMRP protein expression. This partnership has not only validated our years-long research but also has resulted in the confirmation of a novel target for FXS, which we hope will lead to much-needed treatment options for FXS patients and their families.' Dr. Berry-Kravis added, 'I am very excited that we will be able to continue development of this potential genetically based disease-modifying FMRP-restoring therapy that is expected to have a major impact on the FXS field and the spectrum of treatment options available to improve function in people with FXS.' An orphan disease, FXS affects approximately 87,000 individuals in the U.S. alone – one in 4,000 men and one in 6,000 women. Though FXS occurs in both genders, males are more frequently affected than females, and generally with greater severity. In addition to intellectual disability, FXS patients endure a wide range of disabling symptoms including severe anxiety, social aversion, hyperactivity and attention deficit, sensory hypersensitivity, aggression, developmental seizures, and others. There are no effective disease-modifying therapies currently available for FXS. ASOs are short, engineered single-stranded DNA/RNA molecules that can selectively bind RNA to regulate its expression in the cell. ASO technology has been leading in the field of protein regulation and has since allowed us to develop treatments for neurodegenerative disease by changing the expression of genes connected to the disease. QurAlis' FlexASO® platform was developed to generate splice-switching ASOs with improved potency, increased therapeutic index and improved bio-distribution. This bespoke platform has the potential to tackle the spectrum of neurodegenerative and neurological diseases. About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure, boldly seeking to translate scientific breakthroughs into powerful precision medicines. We work collaboratively with a relentless pursuit of knowledge, precise attention to craft, and compassion to discover and develop medicines that have the potential to transform the lives of people living with neurodegenerative and neurological diseases. QurAlis is the leader in development of precision therapies for amyotrophic lateral sclerosis (ALS). In addition to ALS, QurAlis is advancing a robust precision medicine pipeline to bring effective disease-modifying therapeutics to patients suffering from severe diseases defined by genetics and clinical biomarkers. For more information, please visit or follow us on X @QurAlisCo or LinkedIn. View source version on CONTACT: Kathy Vincent [email protected] 310-403-8951 KEYWORD: UNITED STATES NORTH AMERICA MASSACHUSETTS INDUSTRY KEYWORD: RESEARCH NEUROLOGY GENETICS BIOTECHNOLOGY HEALTH UNIVERSITY PHARMACEUTICAL SCIENCE EDUCATION SOURCE: QurAlis Corporation Copyright Business Wire 2025. PUB: 05/15/2025 07:45 AM/DISC: 05/15/2025 07:44 AM
Business Wire
15-05-2025
- Business
- Business Wire
QurAlis Announces Exclusive License on Novel Mechanism for Fragile X Syndrome (FXS) to Enable Development of First Potential Disease-Modifying Therapy
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- QurAlis Corporation ('QurAlis'), a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of neurodegenerative and neurological diseases, today announced it has entered into an exclusive license agreement with UMass Chan Medical School ('UMass Chan') on a novel RNA-targeted mechanism confirmed to restore functional protein for Fragile X syndrome (FXS). Fragile X syndrome is the leading inherited form of intellectual disability and the most common single genetic cause of autism. It is a genetic condition caused by a mutation of a single gene – Fragile X messenger ribonucleoprotein 1 (FMR1) – on the X chromosome. This mutation of FMR1 causes a range of developmental problems including learning disabilities, behavioral challenges, and cognitive impairment. QurAlis' exclusive license agreement is a result of its 2024 partnership and collaboration with UMass Chan to explore the biology of FXS to determine and confirm relevant targets that could enable antisense oligonucleotide (ASO)-mediated correction for FXS. QurAlis leveraged its deep understanding, knowledge and expertise in developing ASOs as part of the collaboration. QurAlis confirmed the findings from the original publication of the UMass Chan researchers and is advancing FMR1 as a precision medicine target in up to 80 percent of FXS patients. The mis-spliced form of FMR1, designated as FMR1-217, is widely expressed throughout cortical brain areas affected in FXS and can be measured in blood and cerebrospinal fluid. Preliminary data suggest biomarker feasibility to detect mis-splicing of FMR1 in patients with FXS. 'FXS is a devastating neurodevelopmental disorder with no effective disease-modifying therapies available. Our initial partnership with UMass Chan confirmed that FMR1-217 is a validated genetic target for FXS,' said Kasper Roet, Ph.D., chief executive officer and co-founder of QurAlis. 'This groundbreaking discovery of a novel RNA-targeted mechanism to restore functional protein for FXS and the feasibility of a biomarker to detect mis-splicing of FMR1 in FXS patients opens up a completely new type of therapeutic approach through splice correction. We look forward to applying QurAlis' FlexASO® platform and deep knowledge and expertise of ASO splicing targets toward having a candidate nominated for IND-enabling studies in the near future, so that we can bring a potential new precision medicine option to patients.' Joel Richter, Ph.D., the Arthur F. Koskinas Chair in Neuroscience and professor of molecular medicine at UMass Chan, and colleagues Sneha Shah, Ph.D., and Jonathan K. Watts, Ph.D., together with Elizabeth Berry-Kravis, M.D., Ph.D., at Rush University Medical Center, have shown that aberrant alternative splicing, or mis-splicing, of messenger RNA (mRNA) plays a fundamental role in FXS. In a seminal publication by the group, it was revealed that in FXS patients, FMR1 mRNA is still being expressed, but is mis-spliced, comprising a short, truncated alternative mRNA variant called FMR1-217 which results in non-functional FMRP protein expression. Working with patient-derived cells, Dr. Richter's lab and Dr. Berry-Kravis initially demonstrated that ASOs can successfully inhibit the mis-splicing, reduce expression of FMR1-217, rescue proper FMR1 mRNA, and restore FMRP protein expression. 'This is a meaningful step in the process of taking basic biological discoveries and turning them into practical therapies that can benefit patients in the clinic,' said Dr. Richter. 'QurAlis' platform and expertise in neurodegenerative disorders are industry leading and well positioned to address the mis-splicing of FMR1 RNA and restore functional FMRP protein expression. This partnership has not only validated our years-long research but also has resulted in the confirmation of a novel target for FXS, which we hope will lead to much-needed treatment options for FXS patients and their families.' Dr. Berry-Kravis added, 'I am very excited that we will be able to continue development of this potential genetically based disease-modifying FMRP-restoring therapy that is expected to have a major impact on the FXS field and the spectrum of treatment options available to improve function in people with FXS.' An orphan disease, FXS affects approximately 87,000 individuals in the U.S. alone – one in 4,000 men and one in 6,000 women. Though FXS occurs in both genders, males are more frequently affected than females, and generally with greater severity. In addition to intellectual disability, FXS patients endure a wide range of disabling symptoms including severe anxiety, social aversion, hyperactivity and attention deficit, sensory hypersensitivity, aggression, developmental seizures, and others. There are no effective disease-modifying therapies currently available for FXS. ASOs are short, engineered single-stranded DNA/RNA molecules that can selectively bind RNA to regulate its expression in the cell. ASO technology has been leading in the field of protein regulation and has since allowed us to develop treatments for neurodegenerative disease by changing the expression of genes connected to the disease. QurAlis' FlexASO® platform was developed to generate splice-switching ASOs with improved potency, increased therapeutic index and improved bio-distribution. This bespoke platform has the potential to tackle the spectrum of neurodegenerative and neurological diseases. About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure, boldly seeking to translate scientific breakthroughs into powerful precision medicines. We work collaboratively with a relentless pursuit of knowledge, precise attention to craft, and compassion to discover and develop medicines that have the potential to transform the lives of people living with neurodegenerative and neurological diseases. QurAlis is the leader in development of precision therapies for amyotrophic lateral sclerosis (ALS). In addition to ALS, QurAlis is advancing a robust precision medicine pipeline to bring effective disease-modifying therapeutics to patients suffering from severe diseases defined by genetics and clinical biomarkers. For more information, please visit or follow us on X @QurAlisCo or LinkedIn.
Yahoo
14-05-2025
- Business
- Yahoo
Kaerus Bioscience's lead candidate KER-0193 granted Orphan Drug Designation and Rare Pediatric Drug Designation by U.S. FDA for treatment of Fragile X syndrome (FXS)
FDA's two designations demonstrate KER-0193's potential as a treatment for FXS Follows the successful completion of Phase 1 clinical trial Fragile X syndrome is the most common cause of inherited autism LONDON, May 14, 2025 /PRNewswire/ -- Kaerus Bioscience ("Kaerus" or "the Company"), a clinical stage biopharmaceutical company created by Medicxi for the development of therapeutics for rare genetic syndromes of neurodevelopment, today announces that its lead candidate KER-0193 has been granted both Orphan Drug Designation and Rare Pediatric Drug Designations for the treatment of Fragile X syndrome (FXS) by the U.S. Food and Drugs Administration (FDA). It follows the recent successful completion of a Phase 1 trial of KER-0193 in healthy volunteers, which confirmed the drug to be safe, well tolerated and exhibit excellent pharmacokinetics. FXS is an inherited condition, affecting about 1 in 7,000 males and 1 in 11,000 females, for which there are currently no approved treatments. It is the most common cause of inherited autism and intellectual disability, accounting for approximately 1 per cent of such cases globally. Dr Robert Ring, CEO of Kaerus Bioscience, said: "The FDA's granting of Orphan Drug Designation and Rare Pediatric Drug Designation for KER-0193 is an important step towards our objective of delivering an effective treatment for people with Fragile X syndrome. "Not only do these two FDA designations affirm the therapeutic potential of KER-0193 in Fragile X syndrome, they also provide Kaerus with access to significant regulatory and financial incentives as we look to progress the drug through clinical trials and ultimately take it to market." Paul Sekhri, Chairman of Kaerus Bioscience, said: "These important FDA designations are more excellent news for Kaerus, coming after the impressive Phase 1 results showing KER-0193 to be safe and well-tolerated. These developments put the Company in a superb position as we look to move into Phase 2 trials." Both FDA programmes are aimed at encouraging the development of treatments for rare diseases. Discovered by Kaerus, KER-0193 is a novel, orally-bioavailable small molecule designed to specifically address hyper-excitability of brain function commonly associated with Fragile X syndrome. KER-0193 does this by targeting BK channels (calcium-activated potassium channels), which have been described as master regulators of excitability across the nervous system. The genetic cause of FXS is directly linked to a reduction in BK channel function. Based on its broad efficacy profile in preclinical genetic models of FXS, Kaerus is excited by the therapeutic potential of KER-0193 to address the diversity of behavioural, sensory and cognitive challenges that adversely impact the lives of individuals with FXS. Kaerus's conviction has been strengthened by a pre-planned sub-study, conducted during the Phase 1 trial, in which the effects of KER-0193 on brain activity in healthy volunteers were investigated using electroencephalography (EEG). The study convincingly demonstrated that KER-0193 enters the brain and produces pharmcodynamic effects on brain activity in regions often implicated in patients with FXS. These results replicated observations from EEG profiling of KER-0193 in preclinical animal studies, demonstrating proof of mechanism. Beyond FXS, reduced BK channel activity has been implicated in a number of other neurological conditions, including epilepsy and several rare genetic epileptic encephalopathies. Dr Ring said: "We are actively exploring opportunities to expand the therapeutic potential of our BK modulator platform to these other indications, where patient populations struggle with significant unmet treatment needs." The company is finalising preparations for a Phase 2 proof-of-concept study in FXS patients. About Kaerus Backed by Medicxi, Kaerus Bioscience Ltd is a clinical-stage biotechnology company committed to turning scientific advances into treatment realities for patients with rare genetic syndromes of neurodevelopment. Kaerus has developed a pipeline of targeted, small molecule therapeutics that address an underlying ion channel dysfunction in Fragile X syndrome, which is the most common inherited cause of intellectual disability and autism globally. For more information about Kaerus, please visit About KER-0193 KER-0193 is a novel, proprietary, and orally-bioavailable small molecule modulator of BK channels discovered by Kaerus. KER-0193 specifically addresses abnormal function of BK channels linked to the genetic cause of Fragile X syndrome. KER-0193 has already demonstrated broad effects on improving syndrome-relevant behavioural, sensory and cognitive deficits observed in genetic animal models of Fragile X. Fragile X syndrome, which affects about 1 in 7,000 males and 1 in 11,000 females, is the most common inherited cause of autism and intellectual disability globally. There are currently no approved treatments for Fragile X. About Medicxi Medicxi is a healthcare-focused investment firm with the mission to create and invest in companies across the full drug development continuum. Leveraging deep expertise in drug development and company creation spanning over two decades, Medicxi invests in early and late-stage therapeutics with a product vision that can fulfil a clear unmet medical more information, please visit: View original content: SOURCE Kaerus Bioscience
Business Wire
06-05-2025
- Business
- Business Wire
Harmony Biosciences Reports Strong Q1 2025 Financial Results, Highlights Advancement of Its Pipeline and Upcoming Catalysts, and Reaffirms 2025 Revenue Guidance
PLYMOUTH MEETING, Pa.--(BUSINESS WIRE)--Harmony Biosciences Holdings, Inc. (Nasdaq: HRMY) today announced strong year-over-year revenue growth for WAKIX® of 20% in the first quarter 2025, on its way to a potential $1B+ opportunity in narcolepsy alone and poised for additional growth from its next-gen pitolisant development programs. The company has demonstrated four consecutive years of profitability and has grown its cash and investments position to over $600M. 'Building off of our strong foundation of commercial success, we are poised for significant momentum throughout the rest of the year, driven by the upcoming catalysts from our robust, late-stage pipeline,' said Jeffrey M. Dayno, M.D., President and Chief Executive Officer of Harmony Biosciences. 'Our next major clinical milestone, topline data readout from our Phase 3 registrational trial of ZYN002 in patients with Fragile X syndrome, the RECONNECT Study, is on track for Q3. A positive readout could put us on a path toward the first ever approved treatment for this patient community. I am proud of the unique profile we have created at Harmony, a profitable, self-funding biotech company, with a robust pipeline, that has the potential to help hundreds of thousands of patients living with unmet medical needs while creating significant, long-term value.' Franchise Highlights Sleep/Wake Franchise WAKIX in Narcolepsy Net Revenue was $184.7 million for Q1 2025 2025 Net Revenue projected between $820 to $860 million The average number of patients on WAKIX increased to approximately 7,200 for Q1 2025 and we exited the quarter with approximately 7,300 patients Pitolisant HD (high-dose) Higher dose and optimized pharmacokinetic profile designed for greater efficacy in narcolepsy; development program to pursue multiple additional indications Phase 3 registrational trial in narcolepsy designed for greater efficacy in excessive daytime sleepiness and cataplexy; also to include endpoint on narcolepsy-related fatigue in pursuit of differentiated label Phase 3 registrational trial in IH to include endpoint on sleep inertia in pursuit of differentiated label On track to initiate Phase 3 registrational trials in both narcolepsy and IH in Q4 2025 with potential PDUFA dates in 2028 Utility patents filed out to 2044 for narcolepsy and IH Pitolisant GR (gastro-resistant) Pivotal bioequivalence study initiated in March 2025 Topline data readout anticipated in Q3 2025 with potential PDUFA date in 2026 Utility patents filed out to 2044 Orexin-2 receptor agonist (BP1.15205) Comprehensive preclinical safety and efficacy data to be presented at SLEEP 2025 (June) Potential to be best-in-class orexin-2 receptor agonist based on a novel chemical scaffold, preclinical potency, selectivity and safety data, as well as its potential for once-a-day dosing IMPD submission on track for mid-2025; first-in-human study expected to initiate 2H 2025 with clinical data anticipated in 2026 Neurobehavioral Franchise ZYN002 Completed recruitment of Phase 3 registrational trial, the RECONNECT Study, in patients with Fragile X syndrome (FXS); on track for topline data readout in Q3 RECONNECT Study is designed to confirm the positive findings from the prespecified analysis of the primary outcome in the subgroup of patients with complete methylation from the Phase 2/3 CONNECT Study Promising new open-label extension (OLE) data shows benefit in patients with FXS Participants in the OLE trial demonstrated clinically meaningful improvements in behavioral symptoms as measured by the Aberrant Behavior Checklist – Community (ABC-C FXS Irritability) More than 60% of participants achieved clinically meaningful improvement of at least 9 points on the ABC-C FXS Irritability scores out to 3 years Potential to be the first and only approved treatment for patients with FXS; 80,000 patients in the U.S. and Harmony possesses global rights Prepared to initiate Phase 3 registrational trial in 22q11.2 deletion syndrome (22q) in Q4 2025 (pending positive data from the RECONNECT Study) Rare Epilepsy Franchise EPX-100 (clemizole hydrochloride) Most advanced development program in the 5HT2 (serotonin) agonist class Recruitment ongoing for Phase 3 registrational trial in Dravet syndrome (ARGUS Study) with topline data anticipated in 2026 Recruitment ongoing for Phase 3 registrational trial in patients with Lennox-Gastaut syndrome (LIGHTHOUSE Study) with topline data anticipated in 2026 EPX-200 (lorcaserin hydrochloride) Proven mechanism of action in developmental and epileptic encephalopathies (DEEs) confirmed via non-clinical and clinical data Currently in IND enabling stage First Quarter 2025 Financial Results Net product revenue for the quarter ended March 31, 2025, was $184.7 million, compared to $154.6 million for the same period in 2024. The 20% growth versus the same period in 2024 is primarily attributed to strong commercial sales of WAKIX driven by continued organic demand tapping into a large market opportunity (approximately 80,000 patients diagnosed with narcolepsy in the U.S.) and the broad clinical utility of WAKIX across the approximately 9,000 HCPs that we call on (about 5,000 of whom do not participate in an oxybate REMS program). GAAP net income for the quarter ended March 31, 2025, was $45.6 million, or $0.78 earnings per diluted share, compared to GAAP net income of $38.3 million, or $0.67 earnings per diluted share, for the same period in 2024. Non-GAAP adjusted net income was $60.4 million, or $1.03 earnings per diluted share, for the quarter ended March 31, 2025, compared to Non-GAAP adjusted net income of $50.7 million, or $0.88 per diluted share, for the same period in 2024. Reconciliations of applicable GAAP financial measures to Non-GAAP financial measures are included at the end of this press release. Harmony's operating expenses include the following: Research and Development expenses were $34.5 million in the first quarter of 2025, as compared to $22.2 million for the same quarter in 2024, representing a 56% increase; Sales and Marketing expenses were $30.7 million in the first quarter of 2025, as compared to $27.2 million for the same quarter in 2024, representing a 13% increase; General and Administrative expenses were $31.2 million in the first quarter of 2025, as compared to $25.7 million for the same quarter in 2024, representing a 22% increase; and Total Operating Expenses were $96.5 million in the first quarter of 2025, as compared to $75.1 million for the same quarter in 2024, representing a 29% increase. As of March 31, 2025, Harmony had cash, cash equivalents and investments of $610.2 million, compared to $576.1 million as of December 31, 2024. 2025 Net Product Revenue Guidance Expect full year 2025 net product revenue of $820 million to $860 million. Conference Call Today at 8:30 a.m. ET We are hosting our first quarter 2025 financial results conference call and webcast today, beginning at 8:30 a.m. Eastern Time. The live and replay webcast of the call will be available on the investor relations page of our website To participate in the live call by phone, dial 800-267-6316 (domestic) or 203-518-9783 (international), and reference passcode HRMYQ125. Non-GAAP Financial Measures In addition to our GAAP results, we present certain Non-GAAP measures including Non-GAAP adjusted net income and Non-GAAP adjusted net income per share, which we believe provides important supplemental information to management and investors regarding our performance. These measurements are not a substitute for GAAP measurements, and the manner in which we calculate Non-GAAP adjusted net income and Non-GAAP adjusted net income per share may not be identical to the manner in which other companies calculate adjusted net income and adjusted net income per share. We use these Non-GAAP measurements as an aid in monitoring our financial performance from quarter-to-quarter and year-to-year and for benchmarking against comparable companies. Non-GAAP financial measures should not be considered in isolation or as a substitute for comparable GAAP measures; should be read in conjunction with our consolidated financial statements prepared in accordance with GAAP; have no standardized meaning prescribed by GAAP; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future there may be other items that we may exclude for purposes of our Non-GAAP financial measures; and we may in the future cease to exclude items that we have historically excluded for purposes of our Non-GAAP financial measures. About WAKIX® (pitolisant) Tablets WAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of EDS in pediatric patients 6 years of age and older with narcolepsy. It was granted orphan drug designation for the treatment of narcolepsy in 2010, and breakthrough therapy designation for the treatment of cataplexy in 2018. WAKIX is a selective histamine 3 (H₃) receptor antagonist/inverse agonist. The mechanism of action of WAKIX is unclear; however, its efficacy could be mediated through its activity at H₃ receptors, thereby increasing the synthesis and release of histamine, a wake promoting neurotransmitter. WAKIX was designed and developed by Bioprojet (France). Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialize pitolisant in the United States. Indications and Usage WAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of excessive daytime sleepiness (EDS) in pediatric patients 6 years of age and older with narcolepsy. Important Safety Information Contraindications WAKIX is contraindicated in patients with known hypersensitivity to pitolisant or any component of the formulation. Anaphylaxis has been reported. WAKIX is also contraindicated in patients with severe hepatic impairment. Warnings and Precautions WAKIX prolongs the QT interval; avoid use of WAKIX in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval. Avoid use in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval. The risk of QT prolongation may be greater in patients with hepatic or renal impairment due to higher concentrations of pitolisant; monitor these patients for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment. WAKIX is contraindicated in patients with severe hepatic impairment and not recommended in patients with end-stage renal disease (ESRD). Adverse Reactions In the placebo-controlled clinical trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and at least twice placebo) for WAKIX were insomnia (6%), nausea (6%), and anxiety (5%). Other adverse reactions that occurred at ≥2% and more frequently than in patients treated with placebo included headache, upper respiratory tract infection, musculoskeletal pain, heart rate increased, hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash. In the placebo-controlled phase of the clinical trial conducted in pediatric patients 6 years and older with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and greater than placebo) for WAKIX were headache (19%) and insomnia (7%). The overall adverse reaction profile of WAKIX in the pediatric clinical trial was similar to that seen in the adult clinical trial program. Drug Interactions Concomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. Reduce the dose of WAKIX by half. Concomitant use of WAKIX with strong CYP3A4 inducers decreases exposure of pitolisant by 50%. Dosage adjustments may be required. H1 receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of WAKIX. Patients should avoid centrally acting H1 receptor antagonists. WAKIX is a borderline/weak inducer of CYP3A4. WAKIX may reduce the effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives. Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with WAKIX and for at least 21 days after discontinuing treatment. Use in Specific Populations There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to WAKIX during pregnancy. Patients should be encouraged to enroll in the WAKIX pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call 1-800-833-7460. The safety and effectiveness of WAKIX have not been established for treatment of excessive daytime sleepiness in pediatric patients less than 6 years of age with narcolepsy. The safety and effectiveness of WAKIX have not been established for treatment of cataplexy in pediatric patients with narcolepsy. WAKIX is extensively metabolized by the liver. WAKIX is contraindicated in patients with severe hepatic impairment. Dosage adjustment is required in patients with moderate hepatic impairment. WAKIX is not recommended in patients with end-stage renal disease. Dosage adjustment of WAKIX is recommended in patients with eGFR <60 mL/minute/1.73 m 2. Dosage reduction is recommended in patients known to be poor CYP2D6 metabolizers; these patients have higher concentrations of WAKIX than normal CYP2D6 metabolizers. Please see the Full Prescribing Information for WAKIX for more information. To report suspected adverse reactions, contact Harmony Biosciences at 1-800-833-7460 or the FDA at 1-800-FDA-1088 or About Narcolepsy Narcolepsy is a rare, chronic, debilitating neurological disease of sleep-wake state instability that impacts approximately 170,000 Americans and is primarily characterized by excessive daytime sleepiness (EDS) and cataplexy – its two cardinal symptoms – along with other manifestations of REM sleep dysregulation (hallucinations and sleep paralysis), which intrude into wakefulness. EDS is the inability to stay awake and alert during the day and is the symptom that is present in all people living with narcolepsy. In most patients, narcolepsy is caused by the loss of hypocretin/orexin, a neuropeptide in the brain that supports sleep-wake state stability. This disease affects men and women equally, with typical symptom onset in adolescence or young adulthood; however, it can take up to a decade to be properly diagnosed. About Idiopathic Hypersomnia Idiopathic Hypersomnia (IH) is a rare and chronic neurological disease that is characterized by excessive daytime sleepiness (EDS) despite sufficient or even long sleep time. EDS in IH cannot be alleviated by naps, longer sleep or more efficient sleep. People living with IH experience significant EDS along with the symptoms of sleep inertia (prolonged difficulty waking up from sleep) and 'brain fog' (impaired cognition, attention, and alertness). The cause of IH is unknown, but it is likely due to alterations in areas of the brain that stabilize states of sleep and wakefulness. IH is one of the central disorders of hypersomnolence and, like narcolepsy, is a debilitating sleep disorder that can result in significant disruption in daily functioning. About ZYN002 ZYN002 is the first-and-only pharmaceutically manufactured synthetic cannabidiol devoid of THC and formulated as a patent-protected permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. The product is manufactured through a synthetic process in a cGMP facility and is not extracted from the cannabis plant. ZYN002 does not contain THC, the compound that causes the euphoric effect of cannabis, and has the potential to be a nonscheduled product if approved. Cannabidiol, the active ingredient in ZYN002, has been granted orphan drug designation by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of FXS and for the treatment of 22q. Additionally, ZYN002 has received FDA Fast Track designation for the treatment of behavioral symptoms in patients with FXS. About Fragile X Syndrome Fragile X syndrome (FXS) is a rare genetic disorder that is the leading known cause of both inherited intellectual disability and autism spectrum disorder. The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. While the exact prevalence is unknown, upwards of 80,000 patients in the U.S. and 121,000 patients in the European Union and the UK are believed to have FXS, based on FXS prevalence estimates of approximately 1 in 4,000 to 7,000 in males and approximately 1 in 8,000 to 11,000 in females. There is a significant unmet medical need in patients living with FXS as there are currently no FDA-approved treatments for this disorder. FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including the endocannabinoid system, and most critically, codes for a protein called FMRP. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat, resulting in deficiency or lack of FMRP. FMRP helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. In people with full mutation of the FMR1 gene, the CGG segment is repeated more than 200 times, and in most cases causes the gene to not function. Methylation of the FMR1 gene also plays a role in determining functionality of the gene. In approximately 60% of patients with FXS, who have complete methylation of the FMR1 gene, no FMRP is produced, resulting in dysregulation of the systems modulated by FMRP. About Clemizole Hydrochloride (EPX-100) EPX-100, clemizole hydrochloride, is under development for the treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). EPX-100 acts by targeting central 5-hydroxytryptamine receptors to modulate serotonin signaling. The drug candidate is administered orally twice a day in a liquid formulation and has been developed based on a proprietary phenotype-based zebrafish drug screening platform. DS is caused by a loss of function mutation in the SCN1A gene, and scn1 mutant zebrafish replicate the genetic etiology and phenotype observed in the majority of DS patients. The scn1Lab mutant zebrafish model that expresses voltage gated sodium channels has been used for high-throughput screening of compounds that modulate Nav1.1 in the central nervous system. About Dravet Syndrome Dravet syndrome (DS) is a severe and progressive epileptic encephalopathy that begins in infancy and causes significant impact on patient functioning. DS begins in the first year of life and is characterized by high seizure frequency and severity, intellectual disability, and a risk of sudden unexpected death in epilepsy. Approximately 85% of Dravet syndrome cases are caused by de novo loss-of-function (LOF) mutations in a voltage-gated sodium channel gene, SCN1A1. DS has an estimated incidence rate of 1:15,700. About Lennox-Gastaut Syndrome Lennox-Gastaut syndrome (LGS) is a rare and drug-resistant epileptic encephalopathy characterized by onset in children between 3-5 years of age. The underlying cause of LGS is unknown and can be related to a wide range of factors including genetic differences and structural differences in the brain. As a result, patients experience multiple seizure types, including atonic seizures, and developmental, cognitive, and behavioral issues. LGS affects approximately 48,000 patients in the U.S. About Harmony Biosciences Harmony Biosciences is a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases who have unmet medical needs. Driven by novel science, visionary thinking, and a commitment to those who feel overlooked, Harmony Biosciences is nurturing a future full of therapeutic possibilities that may enable patients with rare neurological diseases to truly thrive. Established by Paragon Biosciences, LLC, in 2017 and headquartered in Plymouth Meeting, Pa., we believe that when empathy and innovation meet, a better future can begin; a vision evident in the therapeutic innovations we advance, the culture we cultivate, and the community programs we foster. For more information, please visit Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding our full year 2025 net product revenue, expectations for the growth and value of WAKIX, plans to submit an sNDA for pitolisant in idiopathic hypersomnia; our future results of operations and financial position, business strategy, products, prospective products, product approvals, the plans and objectives of management for future operations and future results of anticipated products. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our commercialization efforts and strategy for WAKIX; the rate and degree of market acceptance and clinical utility of pitolisant in additional indications, if approved, and any other product candidates we may develop or acquire, if approved, including ZYN002 and EPX-100; our research and development plans, including our plans to explore the therapeutic potential of pitolisant in additional indications; our ongoing and planned clinical trials; our ability to expand the scope of our license agreements with Bioprojet Société Civile de Recherche ('Bioprojet'); the availability of favorable insurance coverage and reimbursement for WAKIX; the timing of, and our ability to obtain, regulatory approvals for pitolisant for other indications as well as any other product candidates; our estimates regarding expenses, future revenue, capital requirements and additional financing needs; our ability to identify, acquire and integrate additional products or product candidates with significant commercial potential that are consistent with our commercial objectives; our commercialization, marketing and manufacturing capabilities and strategy; significant competition in our industry; our intellectual property position; loss or retirement of key members of management; failure to successfully execute our growth strategy, including any delays in our planned future growth; our failure to maintain effective internal controls; the impact of government laws and regulations; volatility and fluctuations in the price of our common stock; the significant costs and required management time as a result of operating as a public company; the fact that the price of Harmony's common stock may be volatile and fluctuate substantially; statements related to our intended share repurchases and repurchase timeframe; and macroeconomic effects and changes in market conditions, including the impact of tariffs, inflation and the risk of recession. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (the "SEC") on February 25, 2025, and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIES (In thousands, except share and per share data) March 31, 2025 2024 ASSETS CURRENT ASSETS: Cash and cash equivalents $ 488,998 $ 453,001 Investments, short-term 17,955 14,185 Trade receivables, net 105,969 83,033 Inventory, net 6,384 7,198 Prepaid expenses 16,470 13,714 Other current assets 6,916 8,121 Total current assets 642,692 579,252 NONCURRENT ASSETS: Property and equipment, net 1,378 1,257 Restricted cash 270 270 Investments, long-term 103,245 108,874 Intangible assets, net 107,302 113,263 Deferred tax asset 194,709 190,398 Other noncurrent assets 5,939 5,886 Total noncurrent assets 412,843 419,948 TOTAL ASSETS $ 1,055,535 $ 999,200 LIABILITIES AND STOCKHOLDERS' EQUITY CURRENT LIABILITIES: Trade payables $ 17,459 $ 13,744 Accrued compensation 7,582 18,776 Accrued expenses 112,701 120,640 Current portion of long-term debt 17,500 16,250 Other current liabilities 19,876 5,672 Total current liabilities 175,118 175,082 NONCURRENT LIABILITIES: Long-term debt, net 158,182 163,016 Other noncurrent liabilities 1,710 1,947 Total noncurrent liabilities 159,892 164,963 TOTAL LIABILITIES 335,010 340,045 COMMITMENTS AND CONTINGENCIES (Note 13) STOCKHOLDERS' EQUITY: Common stock—$0.00001 par value; 500,000,000 shares authorized at March 31, 2025 and December 31, 2024, respectively; 57,393,673 and 57,144,887 shares issued and outstanding at March 31, 2025 and December 31, 2024, respectively 1 1 Additional paid in capital 672,503 656,872 Accumulated other comprehensive income 245 66 Retained earnings 47,776 2,216 TOTAL STOCKHOLDERS' EQUITY 720,525 659,155 TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY $ 1,055,535 $ 999,200 Expand HARMONY BIOSCIENCES HOLDINGS, INC. AND SUBSIDIARIES (In thousands except share and per share data) Three Months Ended March 31, March 31, 2025 2024 GAAP net income $ 45,560 $ 38,334 Non-GAAP Adjustments: Non-cash interest expense (1) 166 180 Depreciation 7 163 Amortization (2) 5,961 5,961 Stock-based compensation expense 12,450 10,434 Income tax effect related to non-GAAP adjustments (3) (3,776 ) (4,350 ) Non-GAAP adjusted net income $ 60,368 $ 50,722 GAAP reported net income per diluted share $ 0.78 $ 0.67 Non-GAAP adjusted net income per diluted share $ 1.03 $ 0.88 Weighted average number of shares of common stock used in non-GAAP diluted per share 58,524,566 57,597,627 Expand (1) Includes amortization of deferred finance charges. (2) Includes amortization of intangible asset related to WAKIX. (3) Calculated using the reported effective tax rate for the periods presented less impact of valuation allowance release and discrete items. Expand
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11-03-2025
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Kaerus Bioscience Successfully Completes Phase 1 Trial and Demonstrates Proof of Mechanism with its Novel BK Channel Modulator KER-0193 being developed for Fragile X Syndrome
LONDON, March 11, 2025 (GLOBE NEWSWIRE) -- Kaerus Bioscience ( a clinical-stage biopharmaceutical company created by Medicxi for the development of therapeutics for rare genetic syndromes of neurodevelopment, today announces the successful completion of its Phase 1 clinical trial of KER-0193, a novel BK channel modulator the company is developing for Fragile X syndrome (FXS) and other neurodevelopmental conditions. In the trial, KER-0193 was found to be safe and well-tolerated in both single ascending dose and multiple ascending dose cohorts involving 56 healthy volunteers. The drug also exhibited an excellent, dose-proportional pharmacokinetic profile across a wide range of doses. A planned biomarker substudy profiling brain activity using electroencephalography (EEG) was also completed as part of the Phase 1 clinical trial. The results of this pharmaco-EEG study revealed significant pharmacodynamic effects of KER-0193 on multiple, translationally-relevant parameters of brain activity, providing clear clinical evidence of central target engagement for KER-0193. Pharmaco-EEG also revealed a unique topography of KER-0193 effects on brain excitability that specifically maps to cortical regions commonly reported as abnormal by EEG in patients with FXS. This pattern of regional effects on brain excitability replicates observations from EEG profiling of KER-0193 in preclinical animal studies, demonstrating proof of mechanism. 'These results are a significant milestone for Kaerus,' said Dr. Robert Ring, CEO, Kaerus Bioscience. 'The data clearly demonstrate our first-in-class BK channel modulator is active in the CNS, and is both safe and well-tolerated. Taken together with the positive 'proof of mechanism' with EEG, we feel extremely excited and confident heading into Phase 2 in the target population.' The company is currently finalizing preparations for a Phase 2 proof of concept study in FXS patients. About Kaerus BioscienceKaerus Bioscience Ltd is a clinical-stage biotechnology company committed to turning scientific advances into treatment realities for patients with rare genetic syndromes of neurodevelopment. Kaerus has developed a pipeline of targeted, small-molecule therapeutics that address an underlying ion channel dysfunction in Fragile X syndrome, the most common inherited cause of intellectual disability and autism globally. About KER-0193KER-0193 is a novel, proprietary, and orally-bioavailable small molecule modulator of BK channels discovered by Kaerus. KER-0193 specifically addresses abnormal function of BK channels linked to the genetic cause of Fragile X syndrome. KER-0193 has already demonstrated broad effects on improving syndrome-relevant behavioral, sensory and cognitive deficits observed in genetic animal models of Fragile X. Fragile X syndrome is the most common inherited cause of autism and intellectual disability globally. There are currently no approved treatments for Fragile X. About MedicxiMedicxi is a healthcare-focused investment firm with the mission to create and invest in companies across the full drug development continuum. Leveraging deep expertise in drug development and company creation spanning over two decades, Medicxi invests in early and late-stage therapeutics with a product vision that can fulfil a clear unmet medical need. For more information, please visit: ContactFor more information, please visit or contact info@
