Scilex Bio, a Controlling Interest of Joint Venture by Scilex Holding Company, Reports KDS2010 a Novel Oral Tablet Phase 2 Trial for Alzheimer’s Disease (AD) Currently Enrolling with U.S. Patient Cohort to be Added in 2025
Scilex Bio announces progress in its Phase 2 clinical trial for KDS2010 (Tisolagiline), a novel oral tablet targeting Alzheimer's disease. The trial, currently enrolling 114 patients in South Korea, will expand to include U.S. patients in 2025. KDS2010 is a new reversible selective monoamine oxidase B (MAO-B) inhibitor that also influences astrocytic GABA inhibition.
The drug has shown promising results in preclinical studies, significantly reducing astrocytic GABA levels and improving learning and memory in mouse models. Phase 1 trials with 88 subjects demonstrated favorable safety and suitable pharmacokinetics for once-daily dosing. The global Alzheimer's drug market is projected to exceed $15 billion by 2030 in major markets.
Scilex Bio annuncia progressi nel suo studio clinico di Fase 2 per KDS2010 (Tisolagiline), un nuovo farmaco orale mirato alla malattia di Alzheimer. Lo studio, attualmente in fase di arruolamento di 114 pazienti in Corea del Sud, si espanderà per includere pazienti statunitensi nel 2025. KDS2010 è un nuovo inibitore selettivo e reversibile della monoamino ossidasi B (MAO-B) che influisce anche sull'inibizione del GABA astrocitario.
Il farmaco ha mostrato risultati promettenti negli studi preclinici, riducendo significativamente i livelli di GABA astrocitario e migliorando l'apprendimento e la memoria nei modelli murini. Gli studi di Fase 1 con 88 soggetti hanno dimostrato un profilo di sicurezza favorevole e una farmacocinetica adeguata per una somministrazione una volta al giorno. Si prevede che il mercato globale dei farmaci per l'Alzheimer supererà $15 miliardi entro il 2030 nei principali mercati.
Scilex Bio anuncia avances en su ensayo clínico de Fase 2 para KDS2010 (Tisolagiline), una nueva tableta oral dirigida a la enfermedad de Alzheimer. El ensayo, que actualmente está inscribiendo a 114 pacientes en Corea del Sur, se expandirá para incluir pacientes en EE. UU. en 2025. KDS2010 es un nuevo inhibidor selectivo y reversible de la monoamina oxidasa B (MAO-B) que también influye en la inhibición del GABA astrocitario.
El fármaco ha mostrado resultados prometedores en estudios preclínicos, reduciendo significativamente los niveles de GABA astrocitario y mejorando el aprendizaje y la memoria en modelos de ratón. Los ensayos de Fase 1 con 88 sujetos demostraron un perfil de seguridad favorable y una farmacocinética adecuada para una dosificación una vez al día. Se proyecta que el mercado global de medicamentos para el Alzheimer superará los $15 mil millones para 2030 en los principales mercados.
Scilex Bio가 KDS2010 (Tisolagiline)의 2상 임상시험 진행 상황을 발표했습니다. 이는 알츠하이머병을 목표로 한 새로운 경구용 정제입니다. 현재 한국에서 114명의 환자를 모집하고 있으며, 2025년에는 미국 환자도 포함될 예정입니다. KDS2010은 모노아민 산화효소 B (MAO-B)의 새로운 선택적 가역 억제제로, 별도로 아교세포 GABA 억제에도 영향을 미칩니다.
이 약물은 전임상 연구에서 유망한 결과를 보여주었으며, 아교세포 GABA 수준을 상당히 줄이고 쥐 모델에서 학습 및 기억을 개선하는 데 기여했습니다. 88명의 피험자를 대상으로 한 1상 시험에서는 안전성이 양호하고 하루 한 번 복용하기에 적합한 약리학적 특성이 입증되었습니다. 글로벌 알츠하이머 치료제 시장은 2030년까지 $150억을 초과할 것으로 전망됩니다.
Scilex Bio annonce des progrès dans son essai clinique de Phase 2 pour KDS2010 (Tisolagiline), un nouveau comprimé oral ciblant la maladie d'Alzheimer. L'essai, qui recrute actuellement 114 patients en Corée du Sud, s'étendra pour inclure des patients aux États-Unis en 2025. KDS2010 est un nouvel inhibiteur sélectif et réversible de la monoamine oxydase B (MAO-B) qui influence également l'inhibition du GABA astrocytaire.
Le médicament a montré des résultats prometteurs dans les études précliniques, réduisant considérablement les niveaux de GABA astrocytaire et améliorant l'apprentissage et la mémoire dans des modèles murins. Les essais de Phase 1 sur 88 sujets ont démontré une sécurité favorable et une pharmacocinétique adéquate pour une posologie quotidienne. Le marché mondial des médicaments pour l'Alzheimer devrait dépasser 15 milliards de dollars d'ici 2030 dans les principaux marchés.
Scilex Bio kündigt Fortschritte in seiner klinischen Phase-2-Studie für KDS2010 (Tisolagiline) an, eine neuartige orale Tablette, die auf Alzheimer abzielt. Die Studie, die derzeit 114 Patienten in Südkorea rekrutiert, wird 2025 auf Patienten in den USA ausgedehnt. KDS2010 ist ein neuer reversibler selektiver Monoaminooxidase B (MAO-B)-Hemmer, der auch die GABA-Inhibition der Astrozyten beeinflusst.
Das Medikament hat in präklinischen Studien vielversprechende Ergebnisse gezeigt und die GABA-Spiegel in Astrozyten erheblich gesenkt sowie das Lernen und das Gedächtnis in Mausmodellen verbessert. Phase-1-Studien mit 88 Probanden haben eine günstige Sicherheit und geeignete Pharmakokinetik für eine einmal tägliche Dosis gezeigt. Es wird erwartet, dass der globale Markt für Alzheimer-Medikamente bis 2030 15 Milliarden Dollar übersteigen wird in den wichtigsten Märkten.
- Phase 1 trials demonstrated favorable safety profile and once-daily dosing potential
- Preclinical studies showed significant improvement in learning and memory in mouse models
- Drug offers unique oral tablet delivery compared to injectable alternatives
- Targeting $15 billion Alzheimer's drug market by 2030
- Phase 2 trial still in early enrollment stages
- U.S. patient cohort delayed until 2025
- No efficacy data in human subjects yet
Insights
The Phase 2 trial of KDS2010 represents a significant advancement in Alzheimer's treatment development, particularly notable for its novel mechanism targeting both MAO-B inhibition and astrocytic GABA regulation. The dual-action approach, combined with the convenience of oral administration, differentiates it from current injectable antibody treatments. The compound has shown promising preclinical results in APP/PS1 mice, demonstrating improved learning and memory outcomes.
The drug's reversible selective MAO-B inhibition mechanism potentially offers advantages over existing irreversible inhibitors like selegiline, addressing the limitations of long-term treatment efficacy. With successful Phase 1 trials showing favorable safety profiles and once-daily dosing potential across different populations, KDS2010 is well-positioned for its ongoing Phase 2 evaluation.
The
This development holds strategic significance for Scilex Holding Company, particularly given the expanding Alzheimer's drug market. The oral administration route could provide a competitive advantage over injectable alternatives, potentially capturing a larger market share if approved. The planned expansion of trials to include U.S. patients in 2025 suggests a methodical approach to market development.
The global Alzheimer's drug market projection of
- Currently enrolling randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial to evaluate the safety and efficacy of KDS2010 in patients with Alzheimer’s disease with mild cognitive impairment and mild dementia is currently recruiting in South Korea in 114 patients and U.S. cohort will be added in 2025.
- KDS2010 (Tisolagiline) is a new reversible selective monoamine oxidase B (MAO-B) inhibitor being studied for its potential in treating neurodegenerative diseases like Alzheimer's disease.
- Apart from its role as a MAO-B inhibitor, it also influences astrocytic GABA inhibition.
- In neurodegenerative diseases like Alzheimer’s, altered GABAergic activity and dysfunction in astrocytic regulation of neurotransmitter systems contribute to cognitive decline and neuroinflammation.
- A highly selective and reversible MAO-B inhibitor, KDS2010 overcomes the disadvantages of the irreversible MAO-B inhibition.
- Long-term treatment with KDS2010 significantly attenuates increased astrocytic GABA levels and astrogliosis, enhances synaptic transmission, and improves learning and memory in APP/PS1 mice.1
- 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 and between Korean and Western population, demonstrating favorable safety and tolerability and adequate pharmacokinetics for once-daily dosing.
- Per Health Care analyst reports 2023, Alzheimer’s global drug market size is expected to rise above
$15 billion by 2030 in the eight major markets, as new drugs show promise and are being launched with FDA approval to slow cognitive decline.2
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 that KDS2010 (Tisolagiline) is a new reversible selective monoamine oxidase B (MAO-B) inhibitor being studied for its potential in treating neurodegenerative diseases like Alzheimer's disease (AD). Apart from its role as a MAO-B inhibitor, it also influences astrocytic GABA inhibition.
“Current treatments in development for Alzheimer’s Disease are mostly injectable antibodies or peptides targeting amyloid, tau or neuroinflammation. Advancement of a small molecule with great potential to improve cognitive function that can be delivered with once-daily oral dosing holds promise for people living with Alzheimer's disease,” said Richard Lipton, MD., Professor of Neurology at the Albert Einstein College of Medicine.
GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the brain, playing a key role in regulating neuronal activity and maintaining balance between excitation and inhibition. Astrocytes, a type of glial cell in the brain, have been shown to be involved in the regulation of GABA activity. In neurodegenerative diseases like Alzheimer’s, altered GABAergic activity and dysfunction in astrocytic regulation of neurotransmitter systems contribute to cognitive decline and neuroinflammation. By inhibiting astrocytic GABA signaling, KDS2010 helps to reduce neuroinflammation and normalize the balance between excitatory and inhibitory signals in the brain, potentially leading to enhancing cognitive function in Alzheimer's disease.
Mechanistically, reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via hydrogen peroxide (H2O2) production. KDS2010 blocks MAO-B-dependent aberrant GABA/ H2O2 production in reactive astrocytes and eliminates neuronal inhibition, neuroinflammation, and neurodegeneration, while enhancing neuroregeneration.3
In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production in reactive astrocytes restores the impaired spike probability, synaptic plasticity, and learning and memory in mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAO-B are significantly upregulated. Selective inhibition of astrocytic GABA synthesis and release is a new therapeutic strategy for treating memory impairment in AD.4
Clinically, short-term treatment with known irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. Interestingly, prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). A highly selective and reversible MAO-B inhibitor, KDS2010 overcomes the disadvantages of the irreversible MAO-B inhibition. Long-term treatment with KDS2010 significantly attenuates increased astrocytic GABA levels and astrogliosis, enhances synaptic transmission, and improves learning and memory in APP/PS1 mice.1
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 and between Korean and Western populations, demonstrating favorable safety and tolerability and adequate pharmacokinetics for once-daily dosing. A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of KDS2010 in Patients with Alzheimer’s Disease with Mild Cognitive Impairment and Mild Dementia is currently recruiting in South Korea in 114 patients and U.S. cohort will be added in 2025.
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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
- Jong-Hyun Park, et al. Science Advances. 2019 Mar 20;5(3):eaav0316
- www.ihealthcareanalyst.com/global-alzheimers-disease-market/
- Heejung Chun, et al. Nature Neuroscience 2020 Dec;23(12):1555-1566
- Seonmi Jo, et al. Nature Medicine. 2014 August ; 20(8): 886–896. doi:10.1038/nm.3639
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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