Scilex Bio, a Controlling Interest of Joint Venture by Scilex Holding Company, Reports Phase 2 Trial for Obesity Currently Enrolling with U.S. Patient Cohort to be Added in 2025. Scilex Bio Reports Positive Results from the Recently Completed Phase 1 Trials Conducted by NeuroBiogen for KDS2010, a Novel Oral Tablet Recently Synthesized Potent, Selective, and Reversible Monoamine Oxidase B inhibitor
Scilex Bio reports progress on its obesity treatment KDS2010, with an ongoing Phase 2 trial currently enrolling approximately 75 overweight or obese patients in South Korea, planning to expand to the U.S. in 2025. The trial is randomized, double-blind, and placebo-controlled. Phase 1 trials, completed with 88 subjects, demonstrated favorable safety, tolerability, and suitable pharmacokinetics for once-daily dosing.
KDS2010 (Tisolagiline) functions as a selective, reversible MAO-B inhibitor, blocking GABA production in reactive astrocytes and eliminating neuronal inhibition in the Lateral Hypothalamic Area. This mechanism stimulates metabolism and energy expenditure without affecting appetite, potentially offering advantages over current obesity treatments like GLP-1 agonists.
Scilex Bio riporta progressi nel suo trattamento per l'obesità KDS2010, con uno studio di Fase 2 in corso che attualmente sta reclutando circa 75 pazienti in sovrappeso o obesi in Corea del Sud, con piani di espansione negli Stati Uniti nel 2025. Lo studio è randomizzato, in doppio cieco e controllato con placebo. Le prove di Fase 1, completate con 88 soggetti, hanno dimostrato una sicurezza favorevole, tollerabilità e una farmacocinetica adeguata per una somministrazione giornaliera.
KDS2010 (Tisolagilina) agisce come un inibitore MAO-B selettivo e reversibile, bloccando la produzione di GABA negli astrociti reattivi ed eliminando l'inibizione neuronale nell'Area Iponatalamica Laterale. Questo meccanismo stimola il metabolismo e il consumo energetico senza influenzare l'appetito, offrendo potenzialmente vantaggi rispetto ai trattamenti attuali per l'obesità come gli agonisti del GLP-1.
Scilex Bio informa sobre el progreso en su tratamiento para la obesidad KDS2010, con un ensayo de Fase 2 en curso que actualmente está reclutando aproximadamente 75 pacientes con sobrepeso u obesidad en Corea del Sur, planeando expandirse a EE. UU. en 2025. El ensayo es aleatorizado, doble ciego y controlado con placebo. Los ensayos de Fase 1, completados con 88 sujetos, demostraron una seguridad favorable, tolerabilidad y una farmacocinética adecuada para una dosificación diaria.
KDS2010 (Tisolagilina) actúa como un inhibidor selectivo y reversible de la MAO-B, bloqueando la producción de GABA en astrocitos reactivos y eliminando la inhibición neuronal en el Área Hipotalámica Lateral. Este mecanismo estimula el metabolismo y el gasto energético sin afectar el apetito, potencialmente ofreciendo ventajas sobre los tratamientos actuales para la obesidad, como los agonistas del GLP-1.
Scilex Bio는 비만 치료제 KDS2010의 진행 상황을 보고하며, 현재 한국에서 약 75명의 과체중 또는 비만 환자를 모집하고 있는 2상 시험을 진행 중이며, 2025년에는 미국으로 확장할 계획입니다. 이 시험은 무작위, 이중 맹검, 위약 대조 방식으로 진행됩니다. 1상 시험은 88명의 피실험자와 함께 완료되었으며, 안전성, 내약성 및 하루 한 번 투여에 적합한 약리학적 특성을 보여주었습니다.
KDS2010 (티솔라질린)은 선택적이고 가역적인 MAO-B 억제제로 작용하며, 반응성 별 아교세포에서 GABA 생성을 차단하고 측좌 시상하부에서 신경 억제를 제거합니다. 이 메커니즘은 식욕에 영향을 주지 않으면서 신진대사와 에너지 소비를 자극하며, GLP-1 작용제와 같은 현재의 비만 치료법에 비해 잠재적인 이점을 제공할 수 있습니다.
Scilex Bio fait état des progrès de son traitement de l'obésité KDS2010, avec un essai de phase 2 en cours qui recrute actuellement environ 75 patients en surpoids ou obèses en Corée du Sud, prévoyant une expansion aux États-Unis en 2025. L'essai est randomisé, en double aveugle et contrôlé par placebo. Les essais de phase 1, réalisés avec 88 sujets, ont démontré une sécurité favorable, une tolérance et une pharmacocinétique appropriée pour une posologie quotidienne.
KDS2010 (Tisolagiline) fonctionne comme un inhibiteur de la MAO-B sélectif et réversible, bloquant la production de GABA dans les astrocytes réactifs et éliminant l'inhibition neurale dans la zone hypothalamique latérale. Ce mécanisme stimule le métabolisme et les dépenses énergétiques sans affecter l'appétit, offrant potentiellement des avantages par rapport aux traitements actuels de l'obésité, comme les agonistes du GLP-1.
Scilex Bio berichtet über Fortschritte bei seiner Adipositasbehandlung KDS2010, mit einer laufenden Phase-2-Studie, die derzeit etwa 75 übergewichtige oder adipöse Patienten in Südkorea rekrutiert und plant, 2025 in die USA zu expandieren. Die Studie ist randomisiert, doppelblind und placebo-kontrolliert. Die Phase-1-Studien, die mit 88 Probanden abgeschlossen wurden, zeigten eine günstige Sicherheit, Verträglichkeit und geeignete Pharmakokinetik für eine einmal tägliche Dosierung.
KDS2010 (Tisolagilin) fungiert als selektiver, reversibler MAO-B-Hemmer, der die GABA-Produktion in reaktiven Astrozyten blockiert und die neuronale Hemmung im lateralen Hypothalamus beseitigt. Dieser Mechanismus stimuliert den Stoffwechsel und den Energieverbrauch, ohne den Appetit zu beeinflussen, und könnte potenziell Vorteile gegenüber aktuellen Adipositasbehandlungen wie GLP-1-Agonisten bieten.
- Successful completion of Phase 1 trials with favorable safety and tolerability profile
- Phase 2 trial actively enrolling patients with planned U.S. expansion
- Novel mechanism of action potentially offering advantages over existing obesity treatments
- Drug demonstrates once-daily dosing capability
- Targeting obesity market projected to reach $150 billion by early 2030s
- U.S. patient cohort addition delayed until 2025
- Phase 2 trial to relatively small sample size of 75 patients
- Early-stage development with significant regulatory hurdles ahead
Insights
The Phase 2 obesity trial for KDS2010 represents a potentially significant advancement in obesity treatment. The drug's novel mechanism targeting MAO-B and astrocytic GABA production offers a distinctly different approach from current GLP-1 agonists. The key differentiator is that KDS2010 stimulates metabolism without suppressing appetite, potentially avoiding common side effects of existing treatments like muscle loss and GI issues. The Phase 1 results showing favorable safety profiles and once-daily dosing feasibility across multiple populations are encouraging. However, with only 75 patients planned for Phase 2, this is still a relatively small trial and efficacy data will be important for market potential assessment.
The obesity drug market presents a massive opportunity, with IQVIA forecasting global sales to reach
- The ongoing obesity Phase 2 trial is a randomized, double-blind, placebo-controlled, dose finding, clinical trial to evaluate the safety and efficacy of KDS2010 in approximately 75 overweight or obese patients currently enrolling in South Korea with a cohort in U.S. to be added in 2025.
- KDS2010 has shown promising preclinical results with a novel mechanism of blocking MAO-B-dependent aberrant GABA (gamma-aminobutyric acid) production in reactive astrocytes and eliminates neuronal inhibition in Lateral Hypothalamic Area, stimulating metabolism and energy expenditure without affecting appetite.
- MAO-B controls tonic levels of GABA, a chief inhibitory neurotransmitter in the central nervous system. Selective inhibition of astrocytic GABA is a new molecular target for treating obesity.
- KDS2010 pharmacokinetics, lack of food effect, safety and dose selection have been characterized in Single Ascending Dose and Multiple Ascending Dose Phase 1 clinical trials with 88 healthy young adults and elderly subjects, demonstrating favorable safety and tolerability and adequate pharmacokinetics for once-daily dosing.
- Several important pharmacological attributes distinguish KDS2010 from molecules of this class.
- Firstly, reversibility of the MAO-B inhibition is critical for long-lasting efficacy. Irreversible inhibitors such as selegiline covalently modify the MAO-B enzyme and destroy the enzyme itself to turn on the compensatory expression of enzyme diamine oxidase, which continues to produce GABA, whereas reversible inhibitor occupies the active site of MAO-B competitively, resulting in an intact MAO-B enzyme with no compensatory mechanism.
- Secondly, only the selective inhibition of MAO-B shown to have selective inhibition of astrocytic GABA, important for anti-obesity effect.
- Lastly, easy penetration of Blood-Brain Barrier by KDS2010 is very important for targeting astrocytes in Lateral Hypothalamic Area.
PALO ALTO, Calif., Dec. 11, 2024 (GLOBE NEWSWIRE) -- Scilex Bio, a controlling interest of joint venture by Scilex Holding Company (Nasdaq: SCLX, “Scilex” or “Company”) with IPMC Company, a representative company of the Bio Innovation Consortium (“IPMC”) which holds the exclusive rights to NeuroBiogen Company’s (“NB”) KDS2010 global license, announced ongoing Phase 2 trial for obesity currently enrolling with U.S. patient cohort to be added in 2025 and positive topline results from the recently completed Phase 1 trials for oral KDS2010, a novel oral tablet small molecule agent.
KDS2010 (Tisolagiline) is a potent, selective, and reversible Monoamine oxidase B (MAO-B) inhibitor of new generation, which overcomes the drawbacks of existing irreversible and reversible MAO-B inhibitors. Recently, a new important mechanism of action was discovered for this class of drugs. In contrast to the traditional belief, MAO-A and MAO-B have profoundly different roles: MAO-A regulates dopamine levels, whereas MAO-B controls tonic levels of GABA, gamma-aminobutyric acid, a chief inhibitory neurotransmitter in the central nervous system. Selective inhibition of astrocytic GABA is a molecular target for treating obesity. This discovery was published in Nature (Hyun-U Cho, et al. 2021).
“It is exciting to see a new oral medication in development for treatment of obesity with the potential of overcoming current limitations of obesity medications. Reducing obesity and related comorbidities, such as heart disease, hypertension, diabetes, fatty liver disease, and dyslipidemia is of paramount importance for health maintenance. A new oral centrally acting once-a-day medication that is safe and effective would be an exciting development,” said David J. Maron, MD, Chief of the Stanford Prevention Research Center, president-elect of the American Society for Preventive Cardiology, Professor at Stanford University School of Medicine.
Individuals with obesity have an imbalance in food intake and energy expenditure, both of which are regulated by neural circuits that work inside the hypothalamus, in particular, in the lateral hypothalamic area (LHA). Astrocytes are glial cells known to be actively involved in the regulatory aspects of metabolic control, such as feeding and uptake of brain glucose. In addition to their physiological role, increasing lines of evidence point to the involvement of hypothalamic astrocytes in the pathogenesis of diet-induced obesity. Consumption of dietary fats induces metabolic damages in hypothalamic neurons. Genetic, pharmacological and electrophysiological evidence of existence of a distinct subpopulation of pacemaker-firing GABAergic neurons was recently discovered. It is a unique population of fat-burning neurons in LHA, regulating energy expenditure via astrocytic GABA without affecting food intake. Pharmacological inhibition of excessive astrocytic GABA synthesis may become a new effective therapeutic strategy for obesity. KDS2010 effectively and rapidly reduced obesity in mice, attenuated the elevated tonic inhibition in LHA, and reduced fats without suppressing appetite. These findings were published in Nature Metabolism (Moonsun Sa, et al. 2023).
Several important pharmacological attributes are distinguishing KDS2010 from other molecules of this class. Firstly, reversibility of the MAO-B inhibition is critical for long-lasting efficacy. Irreversible inhibitors such as selegiline covalently modify the MAO-B enzyme and destroy the enzyme itself to turn on the compensatory expression of enzyme diamine oxidase, which continues to produce GABA, whereas reversible inhibitor occupies the active site of MAO-B competitively, resulting in an intact MAO-B enzyme with no compensatory mechanism. Secondly, only the selective inhibition of MAO-B shown to have selective inhibition of astrocytic GABA, important for anti-obesity effect. And thirdly, easy penetration of Blood-Brain Barrier by KDS2010 is very important for targeting LHA astrocytes.
Several neuron-target obesity drugs were shown to be effective, but they suppress appetite and were withdrawn from the market or not used due serious safety risks, including cardiovascular and psychiatric complications. The current mainstay of obesity treatment, GLP-1 agonists, are associated with loss of appetite, gastrointestinal side effects, loss of muscle mass, depression, re-bound effect, and drug-resistance. KDS2010 has a potential to overcome these limitations and risks associated with GLP-1 agonists.
KDS2010 pharmacokinetics, lack of food effect, safety and dose selection has been characterized in Single Ascending Dose and Multiple Ascending Dose studies with approximately 90 patients, demonstrating favorable safety profile and tolerability. KDS2010 showed well tolerated and safe for single dose (30 to 960mg) and repeated dosing over 7 days (60 to 480mg) and has adequate pharmacokinetics for once-daily with dose-dependence in the range of 60 to 480mg for repeat dosing. KDS2010 also showed no significant differences in safety/tolerability and pharmacokinetics in healthy adults and the elderly, and between Korean and Western populations, with adequate pharmacokinetics for once-daily dosing.
A Randomized, Double-blind, Placebo-controlled, Dose Finding, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of KDS2010 in Overweight or Obese Patients is ongoing in South Korea and will be expanding to the USA in 2025. The trial investigates 12-week treatment in 75 patients with high BMI (Body Mass Index) and at least one of the weight-related comorbidities (hypertension, dyslipidaemia, or cardiovascular disease), assessing body weight change from the baseline, proportion of patients with reduction in body weight, and other parameters.
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“We are very excited to acquire a New Chemical Entity molecule of known drug class, representing a new generation of MAO-B inhibitors, with a newly discovered central mechanism of action relevant for multiple neurological, analgesic and cardiometabolic indications. We are looking forward working with our partners to advance Tisolagiline development starting with adding a cohort of patients in the USA for the current obesity treatment trial,” said Dmitri Lissin, MD, Chief Medical Officer of Scilex Holding Company.
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About Scilex Holding Company
Scilex Holding Company is an innovative revenue-generating company focused on acquiring, developing and commercializing the treatment for neurodegenerative and cardiometabolic diseases, and non-opioid pain management products for the treatment of acute and chronic pain. Scilex targets indications with high unmet needs and large market opportunities with non-opioid therapies for the treatment of patients with acute and chronic pain and are dedicated to advancing and improving patient outcomes. Scilex’s commercial products include: (i) ZTlido® (lidocaine topical system)
In addition, Scilex has three product candidates: (i) SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (“SEMDEXA™” or “SP-102”), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, for which Scilex has completed a Phase 3 study and was granted Fast Track status from the FDA in 2017; (ii) SP-103 (lidocaine topical system)
Scilex Holding Company is headquartered in Palo Alto, California.
For more information on Scilex Holding Company, refer to www.scilexholding.com
About Semnur Pharmaceuticals, Inc.
Semnur Pharmaceuticals, Inc. (“Semnur”) is a clinical-late stage specialty pharmaceutical company focused on the development and commercialization of novel non-opioid pain therapies. Semnur’s lead program, SP-102 (SEMDEXA™), is the first non-opioid novel gel formulation administered epidurally in development for patients with moderate to severe chronic radicular pain/sciatica.
Semnur Pharmaceuticals, Inc. is headquartered in Palo Alto, California.
For more information on Semnur Pharmaceuticals, refer to www.semnurpharma.com
About Scilex Bio
Scilex Holding Company and IPMC Company, a representative company of the Bio Innovation Consortium (“BOIC”), which holds the exclusive rights to NeuroBiogen Company’s (“NB”) KDS2010 global license, formed a joint venture, Scilex Bio, to develop and commercialize a next-generation reversible MAO-B Inhibitor, a novel inhibitor of aberrant GABA production in reactive astrocytes for the treatment of obesity and neurodegenerative diseases including Alzheimer’s disease.
About IPMC
IPMC is a private biopharmaceutical company focused on the development of new medicines for the treatment of cardiometabolic and neurodegenerative diseases.
Forward-Looking Statements
This press release and any statements made for and during any presentation or meeting concerning the matters discussed in this press release contain forward-looking statements related to Scilex and its subsidiaries and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding the Scilex and its subsidiaries, including but not limited to, statements regarding the terms of the potential licensing transaction, statements regarding KDS2010 and the potential efficacy and preclinical results, the potential for KDS2010 to be an innovative new treatment for obesity and Alzheimer’s disease benefitting people living with neurodegenerative and cardiometabolic diseases, the potential market size and growth opportunity for the weight loss and Alzheimer’s global drug market, the Company’s outlook, goals and expectations for 2024, and the Company’s development and commercialization plans. Although each of Scilex and its subsidiaries believes that it has a reasonable basis for each forward-looking statement contained in this press release, each of Scilex and its subsidiaries caution you that these statements are based on a combination of facts and factors currently known and projections of the future, which are inherently uncertain.
Risks and uncertainties that could cause actual results of Scilex to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: the inability of the parties to consummate the licensing transaction for any reason, including any failure to satisfy or waive any closing conditions; changes in the structure, timing and completion of the proposed transaction between Scilex and NeuroBiogen; the ability of the parties to achieve the benefits of the proposed licensing transaction, risks related to the outcome of any legal proceedings that may be instituted against the parties following the announcement of the proposed licensing transaction; risks associated with the unpredictability of trading markets; general economic, political and business conditions; the risk that the potential product candidates that Scilex or Scilex Bio develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Scilex’s and Scilex Bio’s product candidates; the risk that Scilex and Scilex Bio will be unable to successfully market or gain market acceptance of its product candidates; the risk that Scilex’s product candidates may not be beneficial to patients or successfully commercialized; the risk that Scilex has overestimated the size of the target patient population, their willingness to try new therapies and the willingness of physicians to prescribe these therapies; risks that the outcome of the trials and studies for SP-102, SP-103 or SP-104 may not be successful or reflect positive outcomes; risks that the prior results of the clinical and investigator-initiated trials of SP-102 (SEMDEXA™), SP-103 or SP-104 may not be replicated; regulatory and intellectual property risks; and other risks and uncertainties indicated from time to time and other risks described in Scilex’s most recent periodic reports filed with the SEC, including its Annual Reports on Form 10-K for the year ended December 31, 2023 and subsequent Quarterly Reports on Form 10-Q that the Company has filed or may file, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and Scilex undertakes no obligation to update any forward-looking statement in this press release except as may be required by law.
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References
SEMDEXA™ (SP-102) is a trademark owned by Semnur Pharmaceuticals, Inc., a wholly-owned subsidiary of Scilex Holding Company. A proprietary name review by the FDA is planned.
ZTlido® is a registered trademark owned by Scilex Pharmaceuticals Inc., a wholly-owned subsidiary of Scilex Holding Company.
Gloperba® is the subject of an exclusive, transferable license to Scilex Holding Company to use the registered trademark.
ELYXYB® is a registered trademark owned by Scilex Holding Company.
Scilex Bio™ is a trademark owned by Scilex Holding Company.
All other trademarks are the property of their respective owners.
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FAQ
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