Pasithea Therapeutics Announces Successful Completion of PAS-004 Chronic Toxicity Studies
Pasithea Therapeutics Corp. (NASDAQ: KTTA) has successfully completed long-term chronic toxicity studies for its lead candidate PAS-004, a next-generation macrocyclic MEK inhibitor. The studies, conducted in rats (6 months) and dogs (9 months), confirm the safety profile observed in prior 28-day toxicity studies. Key findings include:
1. Establishment of 0.5 mg/kg as the no adverse effect level (NOAEL) in dogs, the most sensitive species.
2. Consistent safety profile at doses correlating with significant pathway engagement.
3. Similar adverse event profile and equivalent NOAEL for crystalline PAS-004 compared to the original amorphous formulation.
These results support chronic patient dosing and highlight PAS-004's potential as a best-in-class MEK inhibitor for treating neurofibromatosis type 1 (NF1) and other cancer indications. Pasithea plans to share initial interim pharmacokinetic and pharmacodynamic data from its Phase 1 clinical study later this quarter.
Pasithea Therapeutics Corp. (NASDAQ: KTTA) ha completato con successo studi di tossicità cronica a lungo termine per il suo candidato principale PAS-004, un inibitore MEK della prossima generazione. Gli studi, condotti su ratti (6 mesi) e cani (9 mesi), confermano il profilo di sicurezza osservato in precedenti studi di tossicità di 28 giorni. I risultati chiave includono:
1. Stabilizzazione di 0,5 mg/kg come livello senza effetti avversi (NOAEL) nei cani, la specie più sensibile.
2. Profili di sicurezza coerenti a dosi correlate a un impegno significativo nel percorso.
3. Profilo di eventi avversi simile e NOAEL equivalente per PAS-004 cristallino rispetto alla formulazione amorfa originale.
Questi risultati supportano la somministrazione cronica ai pazienti e evidenziano il potenziale di PAS-004 come inibitore MEK di classe superiore per il trattamento della neurofibromatosi di tipo 1 (NF1) e altre indicazioni oncologiche. Pasithea prevede di condividere i dati farmaco-cinetici e farmacodinamici iniziali dal suo studio clinico di Fase 1 più avanti in questo trimestre.
Pasithea Therapeutics Corp. (NASDAQ: KTTA) ha completado con éxito estudios de toxicidad crónica a largo plazo para su candidato principal PAS-004, un inhibidor de MEK de nueva generación. Los estudios, realizados en ratas (6 meses) y perros (9 meses), confirman el perfil de seguridad observado en estudios de toxicidad previos de 28 días. Los hallazgos clave incluyen:
1. Establecimiento de 0,5 mg/kg como el nivel sin efectos adversos (NOAEL) en perros, la especie más sensible.
2. Perfil de seguridad consistente a dosis que correlacionan con un compromiso significativo de la vía.
3. Perfil de eventos adversos similar y NOAEL equivalente para PAS-004 cristalino en comparación con la formulación amorfa original.
Estos resultados respaldan la dosificación crónica en pacientes y resaltan el potencial de PAS-004 como un inhibidor de MEK de primera clase para el tratamiento de la neurofibromatosis tipo 1 (NF1) y otras indicaciones oncológicas. Pasithea planea compartir datos farmacocinéticos y farmacodinámicos interinos iniciales de su estudio clínico de Fase 1 más adelante en este trimestre.
Pasithea Therapeutics Corp. (NASDAQ: KTTA)는 차세대 매크로사이클 MEK 억제제인 주요 후보 PAS-004에 대한 장기 만성 독성 연구를 성공적으로 완료했습니다. 6개월간 쥐와 9개월간 개를 대상으로 진행한 연구는 이전 28일 독성 연구에서 관찰된 안전성 프로파일을 확인합니다. 주요 발견 사항은 다음과 같습니다:
1. 개, 즉 가장 민감한 종에서 0.5 mg/kg을 부작용 없음 수준(NOAEL)으로 설정.
2. 중요한 경로 참여와 관련된 용량에서 일관된 안전성 프로파일.
3. 원래 비정형 제형과 비교하여 결정형 PAS-004의 유사한 부작용 프로파일과 동등한 NOAEL.
이 결과는 만성 환자 투여를 지원하며 PAS-004가 신경섬유종증 1형(NF1) 및 기타 암 적응증 치료를 위한 최고급 MEK 억제제의 잠재력을 강조합니다. Pasithea는 이 분기에 1상 임상 연구에서 초기 중간 약동학 및 약리학적 데이터를 공유할 계획입니다.
Pasithea Therapeutics Corp. (NASDAQ: KTTA) a réussi à mener à bien des études de toxicité chronique à long terme pour son candidat principal PAS-004, un inhibiteur MEK de nouvelle génération. Les études, réalisées sur des rats (6 mois) et des chiens (9 mois), confirment le profil de sécurité observé dans les études de toxicité antérieures de 28 jours. Les résultats clés incluent :
1. Établissement de 0,5 mg/kg comme niveau d'absence d'effets indésirables (NOAEL) chez les chiens, l'espèce la plus sensible.
2. Profil de sécurité cohérent à des doses corrélées à un engagement significatif du chemin.
3. Profil d'événements indésirables similaire et NOAEL équivalent pour le PAS-004 cristallin par rapport à la formulation amorphe d'origine.
Ces résultats soutiennent la posologie chronique chez les patients et soulignent le potentiel de PAS-004 en tant qu'inhibiteur MEK de référence pour le traitement de la neurofibromatose de type 1 (NF1) et d'autres indications oncologiques. Pasithea prévoit de partager des données préliminaires de pharmacocinétique et de pharmacodynamique issues de son étude clinique de Phase 1 plus tard dans ce trimestre.
Pasithea Therapeutics Corp. (NASDAQ: KTTA) hat erfolgreich langfristige chronische Toxizitätsstudien für seinen Hauptkandidaten PAS-004, einen innovativen Makrocyclischen MEK-Inhibitor, abgeschlossen. Die Studien, die an Ratten (6 Monate) und Hunden (9 Monate) durchgeführt wurden, bestätigen das Sicherheitsprofil, das in früheren 28-tägigen Toxizitätsstudien beobachtet wurde. Schlüsselergebnisse umfassen:
1. Festlegung von 0,5 mg/kg als das Niveau ohne nachweisbare Nebenwirkungen (NOAEL) bei Hunden, der empfindlichsten Art.
2. Konsistentes Sicherheitsprofil bei Dosen, die mit einem signifikanten Engagement des Weges korrelieren.
3. Ähnliches Nebenwirkungsprofil und gleichwertiger NOAEL für kristallines PAS-004 im Vergleich zur ursprünglichen amorphen Formulierung.
Diese Ergebnisse unterstützen die chronische Dosierung bei Patienten und heben das Potenzial von PAS-004 als best-in-class MEK-Inhibitor zur Behandlung der Neurofibromatose Typ 1 (NF1) und anderer Krebsindikationen hervor. Pasithea plant, spät in diesem Quartal erste vorläufige pharmakokinetische und pharmakodynamische Daten aus seiner klinischen Studie der Phase 1 zu teilen.
- Successful completion of long-term chronic toxicity studies for PAS-004
- Established 0.5 mg/kg as the no adverse effect level (NOAEL) in dogs
- Consistent safety profile at doses correlating with significant pathway engagement
- Similar adverse event profile for crystalline PAS-004 compared to amorphous formulation
- Potential for enhanced efficacy with manageable side effects and less toxicity compared to other MEK inhibitors
- None.
Insights
The successful completion of long-term chronic toxicity studies for PAS-004 is a significant milestone for Pasithea Therapeutics. The results, showing a consistent safety profile in both rats and dogs over extended periods (6 and 9 months respectively), are encouraging for the drug's potential in treating neurofibromatosis type 1 (NF1) and other cancers.
Key points to consider:
- The established no adverse effect level (NOAEL) of
0.5 mg/kg in dogs indicates a favorable safety margin for human dosing. - The crystalline form of PAS-004 demonstrated equivalent safety to the amorphous formulation, which is important for clinical applications.
- The drug's ability to achieve significant pathway engagement below the NOAEL suggests potential for efficacy without compromising safety.
These findings support the progression to chronic patient dosing, a critical step in drug development. However, investors should note that while promising, these are preclinical results and human trials may yield different outcomes.
The development of PAS-004 as a next-generation macrocyclic MEK inhibitor is noteworthy in the oncology field. MEK inhibitors have shown promise in treating various cancers, particularly those with MAPK pathway alterations. The key advantages of PAS-004 appear to be:
- Sustained MAPK pathway suppression: This could lead to enhanced efficacy compared to existing MEK inhibitors.
- Potentially improved side effect profile: The ability to titrate doses while maintaining efficacy might result in better tolerability.
- Versatility: Its potential in both NF1 and other cancer indications broadens its market potential.
The upcoming interim PK/PD data from the Phase 1 trial will be important in validating these preclinical findings in humans. If successful, PAS-004 could potentially address some of the limitations of current MEK inhibitors, offering a new treatment option for patients with MAPK pathway-driven cancers.
MIAMI, Sept. 09, 2024 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (NASDAQ: KTTA) (“Pasithea” or the “Company”), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications, today announced the successful completion of long-term chronic toxicity studies in both rats and dogs with its lead candidate PAS-004, currently being investigated in a Phase 1 clinical trial in advanced cancer patients.
Results show that once daily treatment with PAS-004 for 6-months in rats and 9-months in dogs at different dose levels confirms the observations of prior 28-day toxicity studies and indicates a similar safety profile following long-term dosing in both species. Further, the 9-month study in dogs established 0.5 mg/kg as the no adverse effect level (NOAEL) in dogs, the most sensitive species. PAS-004 demonstrated a consistent safety profile at doses that correlate with significant pathway engagement and will likely produce significant pERK reduction when dosed below the NOAEL. Completion of this milestone is planned to support chronic patient dosing.
For the chronic toxicity studies, PAS-004 was administered in crystalline form and demonstrated a similar adverse event profile and equivalent NOAEL in dogs as compared to the original amorphous formulation. The Company is using a crystalline form of PAS-004 in its human clinical trials.
“It is our belief that the ability to titrate to and obtain sustained Mitogen Associated Protein kinase (MAPK) pathway suppression over a prolonged period will lead to enhanced efficacy with a more manageable side effect profile and less toxicity than that observed with other MEK inhibitors. The results of these long-term chronic toxicity studies further demonstrates PAS-004 safety profile and highlight PAS-004’s potential as a best-in-class MEK inhibitor. We look forward to sharing additional data on PAS-004, including initial interim pharmacokinetic (PK) and pharmacodynamic (PD) data from our first-in-human Phase 1 clinical study later this quarter.” commented Dr. Tiago Reis Marques, CEO of Pasithea.
About Pasithea Therapeutics Corp.
Pasithea is a clinical-stage biotechnology company focused on the discovery, research and development of innovative treatments for central nervous system (CNS) disorders and RASopathies. With an experienced team of experts in the fields of neuroscience, translational medicine, and drug development, Pasithea is developing new molecular entities for the treatment of neurological disorders, including Neurofibromatosis type 1 (NF1), Solid Tumors, and Amyotrophic Lateral Sclerosis (ALS).
Forward Looking Statements
This press release contains statements that constitute “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include all statements, other than statements of historical fact, regarding the Company’s current views and assumptions with respect to future events regarding its business, as well as other statements with respect to the Company’s plans, assumptions, expectations, beliefs and objectives, the success of the Company’s current and future business strategies, product development, preclinical and clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of the Company. While the Company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the Company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties, including factors set forth in the Company’s most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other filings made with the U.S. Securities and Exchange Commission (SEC). Thus, actual results could be materially different. The Company undertakes no obligation to update these statements whether as a result of new information, future events or otherwise, after the date of this release, except as required by law.
Pasithea Therapeutics Contact
Patrick Gaynes
Corporate Communications
pgaynes@pasithea.com
FAQ
What are the results of Pasithea Therapeutics' (KTTA) chronic toxicity studies for PAS-004?
How does the crystalline form of PAS-004 compare to the amorphous formulation in Pasithea's (KTTA) studies?
When will Pasithea Therapeutics (KTTA) release interim data from its Phase 1 clinical study of PAS-004?
What potential advantages does PAS-004 offer over other MEK inhibitors according to Pasithea (KTTA)?
