PureTech Presents Data for LYT-200 (anti-galectin-9 monoclonal antibody) for Relapsed/Refractory AML/MDS at the 2024 ASH Annual Meeting
PureTech Health presented data from its Phase 1b trial of LYT-200, a first-in-class anti-galectin-9 monoclonal antibody, for treating relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the 2024 ASH Annual Meeting.
The trial evaluated LYT-200 both as monotherapy and in combination with venetoclax and hypomethylating agents. In monotherapy, 59% of 22 evaluable patients achieved stable disease or better, with two partial responses. In combination therapy, 80% of 15 evaluable patients achieved stable disease or better, including two complete responses.
The treatment showed a favorable safety profile across all dose levels with no dose-limiting toxicities. The mean duration of treatment exceeded two months in both arms, surpassing the standard survival rate for venetoclax/HMA-refractory patients.
PureTech Health ha presentato dati dal suo studio di Fase 1b di LYT-200, un anticorpo monoclonale anti-galectina-9 di prima classe, per il trattamento della leucemia mieloide acuta (AML) e delle sindromi mielodisplastiche (MDS) recidivante/refrattaria al 2024 ASH Annual Meeting.
Lo studio ha valutato LYT-200 sia come monoterapia che in combinazione con venetoclax e agenti ipometilanti. Nella monoterapia, il 59% dei 22 pazienti valutabili ha raggiunto una malattia stabile o meglio, con due risposte parziali. Nella terapia combinata, l'80% dei 15 pazienti valutabili ha ottenuto una malattia stabile o meglio, incluse due risposte complete.
Il trattamento ha mostrato un profilo di sicurezza favorevole a tutti i livelli di dosaggio senza tossicità limitanti per il dosaggio. La durata media del trattamento ha superato i due mesi in entrambi i gruppi, superando il tasso di sopravvivenza standard per i pazienti refrattari a venetoclax/HMA.
PureTech Health presentó datos de su ensayo de Fase 1b de LYT-200, un anticuerpo monoclonal anti-galectina-9 de primera clase, para el tratamiento de la leucemia mieloide aguda (AML) y de los síndromes mielodisplásicos (MDS) en recaída/refractario en la reunión anual ASH 2024.
El ensayo evaluó LYT-200 tanto como monoterapia como en combinación con venetoclax y agentes hipometilantes. En monoterapia, el 59% de 22 pacientes evaluables lograron enfermedad estable o mejor, con dos respuestas parciales. En la terapia de combinación, el 80% de 15 pacientes evaluables lograron enfermedad estable o mejor, incluyendo dos respuestas completas.
El tratamiento mostró un perfil de seguridad favorable en todos los niveles de dosis sin toxicidades limitantes de dosis. La duración media del tratamiento superó los dos meses en ambos grupos, superando la tasa de supervivencia estándar para los pacientes refractarios a venetoclax/HMA.
PureTech Health는 2024 ASH 연례 회의에서 재발/불응성 급성 골수성 백혈병(AML) 및 골수 이형성 증후군(MDS) 치료를 위한 1상 1b 시험에서 LYT-200, 최초의 anti-galectin-9 단일클론 항체에 대한 데이터를 발표했습니다.
이 시험은 LYT-200을 단독 요법과 venetoclax 및 저메틸화 제제와의 병용 요법 모두에서 평가했습니다. 단독 요법에서 22명의 평가 가능한 환자 중 59%가 안정성 병변 또는 그 이상의 결과를 달성했으며, 두 명의 부분 반응이 있었습니다. 병용 요법에서는 15명의 평가 가능한 환자 중 80%가 안정성 병변 또는 그 이상의 결과를 달성했으며, 두 명의 완전 반응이 포함되었습니다.
치료는 모든 용량 수준에서 유리한 안전성 프로필을 보여주었으며, 용량 제한 독성은 없었습니다. 치료의 평균 지속 시간은 두 달을 초과하여 venetoclax/HMA에 불응성 환자에 대한 표준 생존율을 초과했습니다.
PureTech Health a présenté des données de son essai de phase 1b de LYT-200, un anticorps monoclonal anti-galectine-9 de première classe, pour le traitement de la leucémie myéloïde aiguë (AML) et des syndromes myélodysplasiques (MDS) en rechute/réfractaire lors de la réunion annuelle ASH 2024.
L'essai a évalué LYT-200 à la fois en monothérapie et en combinaison avec le venetoclax et des agents hypométhylants. En monothérapie, 59 % des 22 patients évaluables ont atteint une maladie stable ou mieux, avec deux réponses partielles. Dans le cadre de la thérapie combinée, 80 % des 15 patients évaluables ont atteint une maladie stable ou mieux, y compris deux réponses complètes.
Le traitement a montré un profil de sécurité favorable à tous les niveaux de dose, sans toxicités limitantes de dose. La durée moyenne du traitement a dépassé deux mois dans les deux groupes, surpassant le taux de survie standard pour les patients réfractaires au venetoclax/HMA.
PureTech Health stellte Daten aus seiner Phase-1b-Studie zu LYT-200, einem einzigartigen Anti-Galectin-9-Monoklonalen Antikörper, zur Behandlung von rezidivierten/refraktären akuten myeloischen Leukämien (AML) und myelodysplastischen Syndromen (MDS) auf dem ASH Jahresmeeting 2024 vor.
Die Studie bewertete LYT-200 sowohl als Monotherapie als auch in Kombination mit Venetoclax und hypomethylierenden Agenzien. In der Monotherapie erreichten 59 % von 22 evaluierten Patienten eine stabile Erkrankung oder besser, einschließlich zwei partieller Ansprechen. In der Kombinationstherapie erreichten 80 % von 15 evaluierten Patienten eine stabile Erkrankung oder besser, einschließlich zwei vollständiger Ansprechen.
Die Behandlung zeigte ein günstiges Sicherheitsprofil über alle Dosisstufen hinweg, ohne dosislimitierende Toxizitäten. Die durchschnittliche Behandlungsdauer überstieg zwei Monate in beiden Gruppen und übertraf die standardmäßige Überlebensrate für Patienten, die refraktär auf Venetoclax/HMA waren.
- 59% of evaluable patients achieved stable disease or better in monotherapy
- 80% of combination therapy patients achieved stable disease or better, including two complete responses
- Favorable safety profile with no dose-limiting toxicities
- Treatment duration exceeded standard survival rate for refractory patients
- Demonstrated efficacy in heavily pre-treated patients with complex mutations
- None.
Insights
LYT-200 is generally safe and well-tolerated as a single agent as well as in combination with standard-of-care venetoclax and hypomethylating agents
LYT-200 demonstrates clinical benefit as a single agent, with two partial responses and
In combination, two complete responses were seen and
Data support LYT-200 as a potential first-line treatment for AML/MDS patients
LYT-200 is currently being evaluated both as a monotherapy and in combination with the standard-of-care venetoclax and hypomethylating agents (HMA) for patients whose disease is relapsed/refractory to at least one line of prior treatment. It targets galectin-9, a glycan-binding protein that is significantly upregulated in AML and MDS and plays a key role in disease development, progression, immune interference and drug resistance. Initial results show a favorable safety profile across both arms and all dose levels with no dose limiting toxicities, as well as evidence of response, hematological improvement and sustained disease management.
“Relapsed/refractory acute myeloid leukemia is one of the most dire cancer diagnoses, with
In the monotherapy arm, patients received LYT-200 at five dose levels (2.0 mg/kg to 16.0 mg/kg). Across all dose levels, LYT-200 induced clinical benefit and responses in heavily pre-treated, relapsed/refractory AML/MDS patients, even in those with complex cytogenetics and mutations such as KRAS, NRAS, BRAF as well as patients previously fully refractory to standard of care. Out of 22 evaluable patients who received monotherapy,
When administered in combination with venetoclax/HMA, results demonstrate that LYT-200 may enhance the efficacy of standard-of-care therapies, even in relapsed or refractory patients. In the combination arm, patients received LYT-200 across three dose levels (4.0 mg/kg to 12.0 mg/kg) with venetoclax/HMA. Out of 15 evaluable patients who received combination therapy,
“Galectin-9 is an essential driver of both disease proliferation and immune suppression in AML that has not yet been addressed therapeutically,” said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. “LYT-200 represents a novel approach for treating AML via a two-gear mode of action that kills cancer cells directly via apoptosis and DNA damage, as well as by re-activating central anti-cancer effectors of the immune system. We are excited by these Phase 1 data that demonstrate the transformative potential of this dual mechanism of LYT-200, both as a single agent and in combination with existing standard-of-care treatments.”
Pharmacodynamic assessments of treated patients, using gene and protein analyses of patient cells, validate the LYT-200 dual mode of action, and reveal AML cellular pathways as well as specific immune cell types which may be most critical for response.
Based on these data, LYT-200 will continue development in relapsed/refractory AML/MDS towards a Phase 2 clinical trial. PureTech previously announced that it intends to advance LYT-200 via its Founded Entity, Gallop Oncology.
About LYT-200
LYT-200 is a fully human IgG4 monoclonal antibody targeting a foundational oncogenic and immunosuppressive protein, galectin-9, for the potential treatment of hematological malignancies and locally advanced metastatic solid tumors, including head and neck cancers, with otherwise poor survival rates. A wide variety of preclinical data support the potential clinical efficacy of LYT-200 and the importance of galectin-9 as a target and suggest a potential opportunity for biomarker development. PureTech has presented data demonstrating high expression of galectin-9 across various solid tumor types and blood cancers and has found that, in several cancers, galectin-9 levels correlate with shorter time to disease relapse and poor survival. Preclinical work also demonstrates single mechanistic and anti-tumor efficacy of LYT-200 in multiple animal and patient-derived tumor cell models. For example, LYT-200 outperforms anti-PD-1 in preclinical models as a single agent. LYT-200 also synergizes with anti-PD-1 in activating CD4 and CD8 T cells in in vivo cancer models. LYT-200 is currently being evaluated in two ongoing Phase 1/2 adaptive design trials for the potential treatment of AML/MDS and head and neck cancers.
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 development plans for LYT-200, potential benefits to patients, 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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1Data as of November 4, 2024, were presented at ASH 2024. Figure reflects additional data generated through November 20, 2024.
2Miyamoto K, Minami Y. Cutting Edge Molecular Therapy for Acute Myeloid Leukemia. Int J Mol Sci. 2020;21(14):5114. Published 2020 Jul 20. doi:10.3390/ijms21145114
3Maiti A, Rausch CR, Cortes JE, et al. Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent and venetoclax regimens. Haematologica. 2021;106(3):894-898. Published 2021 Mar 1. doi:10.3324/haematol.2020.252569
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