PureTech Founded Entity Seaport Therapeutics Presents Additional Data from Phase 1 Study of SPT-300 at ACNP Annual Meeting 2024
Seaport Therapeutics, a PureTech Founded Entity, presented additional data from its Phase 1 study of SPT-300 at the ACNP Annual Meeting 2024. The study, involving 99 participants, evaluated an oral prodrug of allopregnanolone designed for treating major depressive disorder. Key findings showed SPT-300 was well-tolerated with mild to moderate adverse effects, achieving blood levels up to nine times greater than unmodified allopregnanolone. The drug demonstrated pharmacodynamic activity through EEG and VOG assessments, with effects peaking at 4 hours post-dose and diminishing within 6-8 hours. Based on these results, SPT-300 is deemed suitable for chronic, nightly dosing in a planned Phase 2b placebo-controlled study.
Seaport Therapeutics, un'entità fondata da PureTech, ha presentato ulteriori dati dal suo studio di Fase 1 su SPT-300 durante l'Annual Meeting 2024 dell'ACNP. Lo studio, che ha coinvolto 99 partecipanti, ha valutato un pro-farmaco orale di allopregnanolone progettato per il trattamento del disturbo depressivo maggiore. I risultati chiave hanno mostrato che SPT-300 è stato ben tollerato con effetti avversi lievi a moderati, raggiungendo livelli ematici fino a nove volte superiori rispetto all'allopregnanolone non modificato. Il farmaco ha dimostrato attività farmacodinamica attraverso valutazioni EEG e VOG, con effetti che raggiungevano il picco a 4 ore dopo la dose e diminuivano entro 6-8 ore. Sulla base di questi risultati, SPT-300 è ritenuto idoneo per un dosaggio cronico notturno in uno studio di Fase 2b controllato con placebo pianificato.
Seaport Therapeutics, una entidad fundada por PureTech, presentó datos adicionales de su estudio de Fase 1 sobre SPT-300 en la Reunión Anual 2024 de la ACNP. El estudio, que involucró a 99 participantes, evaluó un profármaco oral de alopregnanolona diseñado para el tratamiento del trastorno depresivo mayor. Los resultados clave mostraron que SPT-300 fue bien tolerado con efectos adversos leves a moderados, alcanzando niveles sanguíneos hasta nueve veces mayores que la alopregnanolona no modificada. El fármaco demostró actividad farmacodinámica a través de evaluaciones de EEG y VOG, con efectos que alcanzaron su punto máximo a las 4 horas después de la dosis y que disminuyeron dentro de las 6 a 8 horas. Basado en estos resultados, se considera que SPT-300 es adecuado para una dosis crónica nocturna en un próximo estudio de Fase 2b controlado con placebo.
Seaport Therapeutics, PureTech가 설립한 기관,은 ACNP 연례 회의 2024에서 SPT-300에 대한 1상 연구의 추가 데이터를 발표했습니다. 이 연구는 99명의 참가자를 포함하여 주요 우울 장애 치료를 위해 설계된 알로프레그난올론의 경구 프로드럭을 평가했습니다. 주요 결과는 SPT-300이 경미한 또는 중간 정도의 부작용과 함께 잘 견뎌졌으며, 비수정 알로프레그난올론보다 최대 9배 높은 혈중 농도를 달성했다는 것을 보여주었습니다. 이 약물은 EEG 및 VOG 평가를 통해 약리학적 활성을 보였으며, 효과는 투여 4시간 후에 최고조에 이르고 6-8시간 내에 감소했습니다. 이러한 결과를 바탕으로, SPT-300은 계획된 2b상 위약 대조 연구에서 만성 야간 투여에 적합한 것으로 평가됩니다.
Seaport Therapeutics, une entité fondée par PureTech, a présenté des données supplémentaires de son étude de Phase 1 sur SPT-300 lors de la réunion annuelle 2024 de l'ACNP. L'étude, impliquant 99 participants, a évalué un pro-drogue oral d'allopregnanolone conçu pour traiter le trouble dépressif majeur. Les résultats clés ont montré que SPT-300 était bien toléré avec des effets indésirables légers à modérés, atteignant des niveaux sanguins jusqu'à neuf fois supérieurs à l'allopregnanolone non modifiée. Le médicament a montré une activité pharmacodynamique à travers des évaluations EEG et VOG, avec des effets atteignant leur pic 4 heures après la dose et diminuant dans les 6-8 heures suivant. Sur la base de ces résultats, SPT-300 est considéré comme approprié pour une posologie chronique nocturne dans une étude de Phase 2b contrôlée par placebo prévue.
Seaport Therapeutics, eine von PureTech gegründete Einheit, präsentierte zusätzliche Daten aus ihrer Phase-1-Studie zu SPT-300 auf der ACNP-Jahrestagung 2024. In der Studie, an der 99 Teilnehmer teilnahmen, wurde ein orales Prodrug von Allopregnanolon bewertet, das zur Behandlung der schweren depressiven Störung entwickelt wurde. Die wichtigen Ergebnisse zeigten, dass SPT-300 gut vertragen wurde, mit leichten bis moderaten Nebenwirkungen und Blutspiegeln, die bis zu neunmal höher waren als bei unmodifiziertem Allopregnanolon. Das Medikament zeigte pharmakodynamische Aktivität durch EEG- und VOG-Bewertungen, wobei die Effekte 4 Stunden nach der Dosis ihren Höhepunkt erreichten und innerhalb von 6-8 Stunden abnahmen. Basierend auf diesen Ergebnissen gilt SPT-300 als geeignet für eine chronische nächtliche Dosierung in einer geplanten Phase-2b-Studie, die mit Placebo kontrolliert werden soll.
- Drug achieved 9x higher blood levels compared to unmodified allopregnanolone
- All adverse events were mild or moderate and transient
- Successfully completed Phase 1 study with 99 participants
- Demonstrated clear pharmacodynamic activity through EEG and VOG assessments
- Most common adverse effect was somnolence (drowsiness)
- Effects require 4 hours to peak, indicating delayed onset of action
Insights
The Phase 1 trial results for SPT-300 demonstrate promising pharmacokinetic and safety profiles that warrant advancement to Phase 2b testing. The key breakthrough is achieving 9x greater bioavailability compared to unmodified allopregnanolone through their prodrug approach. This addresses a critical limitation that has historically prevented oral administration of allopregnanolone.
The pharmacodynamic data showing EEG changes and reduced saccadic eye velocity at 4 hours post-dose, aligning with peak somnolence, provides concrete evidence of GABAA receptor engagement. The mild and transient nature of adverse events, primarily somnolence resolving within 6-8 hours, supports the planned nighttime dosing strategy for the Phase 2b trial. This could provide a significant advantage over existing rapid-acting antidepressants that often have challenging side effect profiles.
While the Phase 1 results are technically positive, investors should maintain measured expectations as this is still early-stage clinical development. The market for depression treatments is highly competitive, though SPT-300's oral formulation and potential for chronic use could provide meaningful commercial differentiation if successful in later trials.
For PureTech shareholders, this represents a positive milestone for one of their Founded Entities, but the impact on PRTC's valuation is likely to be in the near term given the early stage. The key value inflection point will be the upcoming Phase 2b trial results in major depressive disorder. Success there would significantly de-risk the program and could drive increased interest from potential commercial partners.
Multiple well-tolerated doses with pharmacodynamic activity were identified and will be included in a planned Phase 2b study in major depressive disorder
New data presented at the conference include further safety analyses and pharmacokinetic and pharmacodynamic data. Based on the Phase 1 study results, the profile of SPT-300 is suitable for chronic dosing and oral administration at night in the planned Phase 2b placebo-controlled study.
The full text of the announcement from Seaport is as follows:
Seaport Therapeutics Presents Additional Data from Phase 1 Study of SPT-300 at ACNP Annual Meeting 2024
Multiple well-tolerated doses with pharmacodynamic activity were identified and will be included in a planned Phase 2b study in major depressive disorder
The Phase 1 study enrolled 99 participants (in three parts: double-blind single ascending dose, multiple ascending dose, and open-label food effect) and evaluated oral bioavailability, safety, tolerability, pharmacokinetics and GABAA target engagement. Pharmacodynamic assessments included quantitative electroencephalography (EEG) analyses of brain function and video-oculography (VOG) assessments of eye movement. SPT-300 was well-tolerated, with all adverse events (AE) being mild or moderate, transient and dose-dependent. The most common AE was somnolence, which was mild and transient in all cases. The study showed that SPT-300 had therapeutically relevant blood levels that were up to approximately nine times greater than published data on orally administered unmodified allopregnanolone, which has minimal bioavailability.
New data in the poster presented at the conference include further safety analyses and pharmacokinetic and pharmacodynamic data. In the Phase 1 study, increases in EEG beta frequency power and reduction in saccadic eye velocity were observed at approximately 4 hours post-dose. Somnolence peaked in this same timeframe and diminished by 6 to 8 hours post-dose, consistent with both pharmacodynamic markers and blood levels of allopregnanolone. Based on the Phase 1 study results, the profile of SPT-300 is suitable for chronic dosing and oral administration at night in the planned Phase 2b placebo-controlled study in major depressive disorder with or without anxious distress.
“Together with previous clinical efficacy data, the further analyses of the Phase 1 study demonstrate that these doses of SPT-300 are well-tolerated and have rapidly acting pharmacodynamic activity. This reinforces our confidence in SPT-300 as an oral modulator of GABAA receptors and as a potential rapidly acting antidepressant and anxiolytic agent,” said Tony Loebel, M.D., Chief Medical Officer and President of Clinical Development of Seaport Therapeutics. “There is a great need for innovative neuropsychiatric medicines, and an oral form of allopregnanolone has the potential to provide important advantages that we believe will allow for once-daily use on a chronic basis. We look forward to the next phase of our clinical development plan for SPT-300.”
About SPT-300
SPT-300 (Glyph allopregnanolone), an oral prodrug of allopregnanolone, an endogenous neurosteroid, is in clinical stage development for the treatment of major depressive disorder (MDD) with or without anxious distress. Allopregnanolone has demonstrated therapeutic benefit in a range of neuropsychiatric conditions, but is currently only approved as an intravenous infusion, which has limited the scope of its clinical use. Using the Glyph™ platform, SPT-300 is designed to retain the activity, potency and the breadth of the natural biological response of endogenous allopregnanolone in an oral form, which has the potential to capture clinically important antidepressant and anxiolytic effects. In a Phase 2a clinical study, SPT-300 demonstrated initial proof-of-concept in a validated clinical model of anxiety in healthy volunteers. SPT-300 also demonstrated oral bioavailability, tolerability and γ-aminobutyric-acid type A (GABAA) receptor target engagement in healthy volunteers in a Phase 1 clinical study.
About Seaport Therapeutics
Seaport Therapeutics is a clinical-stage biopharmaceutical company advancing the development of novel neuropsychiatric medicines in areas of high unmet patient needs. The Company has a proven strategy of advancing clinically validated mechanisms previously held back by limitations that are overcome with its proprietary Glyph technology platform. All the therapeutic candidates in its pipeline of potentially first and best-in-class medicines are based on the Glyph platform, which is uniquely designed to enable oral bioavailability, bypass first-pass metabolism and reduce liver enzyme elevations or hepatotoxicity and other side effects. Seaport is led by an experienced team that invented and advanced important neuropsychiatric medicines and is guided by an extensive network of renowned scientists, clinicians and key opinion leaders. For more information, please visit www.seaporttx.com.
About PureTech Health
PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 29 therapeutics and therapeutic candidates, including three that have been approved by the
For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh.
Cautionary Note Regarding Forward-Looking Statements
This press release contains statements that are or may be 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 without limitation those related to Seaport’s development plans for its pipeline of therapeutics for the treatment of depression, anxiety and other neuropsychiatric disorders, potential benefits to patients, and Seaport’s and our future prospects, developments and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2023, filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.
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