LYT-200 / PureTech - LARVOL DELTA

LYT-200-2022-02: A Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: PureTech | Trial completion date: May 2025 ➔ Mar 2026 | Trial primary completion date: Feb 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

PureTech Announces Annual Results for Year Ended December 31, 2024 (Businesswire) - P1b/2 | N=44 | NCT04666688 | Sponsor: PureTech | "In the 2025 post-period, the Phase 1b trial evaluating LYT-200 as a monotherapy and in combination with tislelizumab for the treatment of locally advanced/metastatic, relapsed/refractory solid tumors including head and neck cancers was successfully completed. LYT-200 demonstrated a favorable safety profile in all cohorts and showed disease control and initial efficacy signals. The trial demonstrated durable responses—including a complete response lasting over two years—in head and neck cancer patients treated with LYT-200 in combination with tislelizumab."

P1 data • Colorectal Cancer • Head and Neck Cancer • Pancreatic Cancer • Urothelial Cancer

PureTech Announces Annual Results for Year Ended December 31, 2024 (Businesswire) - P1b | N=90 | NCT05829226 | Sponsor: PureTech | "LYT-200 is currently being evaluated in an ongoing Phase 1b trial in relapsed/refractory AML and MDS, both as a monotherapy and in combination with venetoclax/hypomethylating agents (HMA). As of the April 2025 post-period, LYT-200 has shown a favorable safety profile across both arms and all dose levels with no dose limiting toxicities, as well as promising clinical efficacy, as characterized by complete and partial responses, hematological improvement, and sustained disease management. Importantly, treatment with LYT-200 in combination with venetoclax/HMA has resulted in 6 complete responses, 1 morphological leukemia-free state, and 50% of patients experiencing stable disease. Topline results are expected in Q3 2025."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

LYT-200-2020-01: LYT-200 Alone and in Combination With Chemotherapy or Tislelizumab in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=44 | Completed | Sponsor: PureTech | Recruiting ➔ Completed | N=80 ➔ 44 | Trial primary completion date: Sep 2024 ➔ Dec 2024

Enrollment change • Trial completion • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

PureTech Receives FDA Fast Track Designation for LYT-200 in Acute Myeloid Leukemia (AML) (Businesswire) - "PureTech Health plc...today announced that the U.S. Food and Drug Administration ('FDA') has granted Fast Track designation to LYT-200, a first-in-class anti-galectin-9 monoclonal antibody, for the treatment of acute myeloid leukemia ('AML')...LYT-200 is the most advanced clinical program against galectin-9 and is being evaluated in two ongoing clinical trials, including: i) Phase 1/2 clinical trial evaluating LYT-200 as a monotherapy and in combination with venetoclax and hypomethylating agents in hematological malignancies, including AML and high-risk myelodysplastic syndrome (MDS)...ii) Phase 1/2 trial in advanced/metastatic solid tumors, including head and neck cancers."

Fast track • Acute Lymphocytic Leukemia

A Phase I Dose Escalation and Expansion Trial of Lyt-200 (a First-In-Class Anti-Galectin-9 Antibody) Alone and in Combination with Venetoclax/HMA in Relapsed/Refractory AML/MDS (ASH 2024) - P1 | "Mature clinical data, full PK and PD analyses will be presented at ASH. Our study supports LYT-200 as a novel, safe and promising therapeutic agent in AML/MDS and provides rationale for dose level selection for further expansion and a Phase 2 program."

Combination therapy • IO biomarker • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor • IDH2 • LGALS9 • PD-1 • TP53

PureTech Presents Data for LYT-200 (anti-galectin-9 monoclonal antibody) for Relapsed/Refractory AML/MDS at the 2024 ASH Annual Meeting (Businesswire) - P1b | N=90 | NCT05829226 | Sponsor: PureTech | "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, 59% achieved stable disease or better with two partial responses. The mean duration on treatment is greater than two months, which exceeds the standard overall survival of approximately 1.7 months in venetoclax/HMA-refractory patients...Out of 15 evaluable patients who received combination therapy, 80% achieved stable disease or better, with two experiencing complete responses and one patient achieving a morphologic leukemia free state (MLFS)."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

PureTech Health plc – Half-Year Report (Businesswire) - "'The Phase 1b clinical trial evaluating LYT-200 in relapsed/refractory AML and MDS patients is ongoing, and we expect additional data from the trial will be presented in a scientific forum in the fourth quarter of 2024. Also, the Phase 1b trial of LYT-200 in combination with tislelizumab in head and neck cancers is ongoing, with additional data expected in the fourth quarter of 2024.'"

P1 data • Acute Myelogenous Leukemia • Head and Neck Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

A Phase I Dose Escalation and Expansion Trial of LYT-200, a Galectin-9 Antibody, in Solid Tumors and AML (IO-SUMMIT EUROPE 2024) - No abstract available

P1 data • Acute Myelogenous Leukemia • Oncology • Solid Tumor • LGALS9

PureTech Receives FDA Fast Track Designation for LYT-200 in Head and Neck Cancers (Businesswire) - "PureTech Health plc...today announced that the U.S. Food and Drug Administration ('FDA') has granted Fast Track designation for LYT-200 in combination with anti-PD1 therapy for the treatment of recurrent/metastatic head and neck squamous cell carcinomas ('head and neck cancers')...It is being evaluated in two ongoing clinical trials: a Phase 1/2 adaptive design trial in advanced/metastatic solid tumors, including head and neck cancers....a Phase 1b clinical trial evaluating LYT-200 as a monotherapy and in combination with venetoclax and hypomethylating agents in hematological malignancies, including acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome."

Fast track designation • Trial status • Head and Neck Cancer • Hematological Malignancies • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

LYT-200 Alone and in Combination With Chemotherapy or Tislelizumab in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: PureTech | Trial completion date: Sep 2024 ➔ Jan 2025 | Trial primary completion date: Mar 2024 ➔ Sep 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

PureTech Receives Orphan Drug Designation for LYT-200 in Acute Myeloid Leukemia (Businesswire) - "PureTech Health plc...announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to LYT-200 for the treatment of AML....LYT-200 is a fully human IgG4 monoclonal antibody (mAb) targeting galectin-9, a potent oncogenic driver in leukemia cells and an immunosuppressive protein."

Orphan drug • Acute Myelogenous Leukemia

A Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: PureTech | N=50 ➔ 90

Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

PureTech Presents Data from Phase 1 Trial of LYT-200 Targeting Galectin-9 in Solid Tumors at the ESMO Immuno-Oncology Congress 2023 (Nasdaq) - "'Galectin-9 is a promising target for the treatment of solid tumors, and the initial results from the LYT-200 Phase 1 trial support its clinical potential,' said Zev Wainberg, M.D..."

Media quote

PureTech Presents Data from Phase 1 Trial of LYT-200 Targeting Galectin-9 in Solid Tumors at the ESMO Immuno-Oncology Congress 2023 (Businesswire) - P1 | N=80 | NCT04666688 | Sponsor: PureTech | "PureTech Health plc...today announced a poster presentation with results from the Phase 1 portion of the Phase 1/2 dose escalation and expansion clinical trial of LYT-200 at the ESMO Immuno-Oncology Congress 2023. LYT-200 is an anti-galectin-9 antibody being evaluated as a monotherapy and in combination with tislelizumab, an anti-PD-1 antibody developed by BeiGene, in metastatic solid tumors, including urothelial and head and neck cancers...The data being presented from an ongoing study including all evaluable patients demonstrate that LYT-200 has a favorable safety profile in all cohorts, including the monotherapy and combination arms, and shows disease control and initial anti-tumor activity in combination with tislelizumab....The monotherapy arm of the trial has been completed, and the clinically relevant dose was selected for the Phase 2 portion of the trial."

P1 data • Trial status • Oncology • Solid Tumor

A phase I dose escalation and expansion trial of LYT-200, a Galectin-9 antibody +/- tislelizumab (ESMO-IO 2023) - P1/2 | "Enrollment into LYT-200 + TIS arms continues. The presentation will include additional safety, PK, PD and efficacy data."

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • LGALS9

PureTech to Present at Two Upcoming Investor Conferences (PharmiWeb) - "LYT-200 (anti-galectin-9 mAb) is currently in development for the treatment of metastatic/locally advanced solid tumors, including urothelial and head and neck cancers, and hematological malignancies, such as acute myeloid leukemia (AML). Progressed a Phase 1b trial of LYT-200 in combination with tislelizumab in urothelial and head and neck cancers. Topline results are expected in 2024. Progressed a Phase 1b trial evaluating LYT-200 as a single agent for the treatment of AML. Initial results from a subset of patients are expected by the end of 2023."

P1 data • Acute Myelogenous Leukemia • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Urothelial Cancer

A Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS) (SITC 2023) - No abstract available

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy. (PubMed, Biomolecules) - "Upon a better understanding of the immunomodulating functions of galectin-3 and -9, their inhibitors, namely, GB1211 and LYT-200, have been selected as candidates for clinical trials. Other galectin members are also included in this review to provide insight into potential candidates for future treatment(s). The pitfalls and limitations of using galectins and their inhibitors are also discussed to cognise their clinical application."

Journal • Review • Immune Modulation • Oncology

A Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: PureTech

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Lyt-200, a Humanized Anti-Galectin-9 Antibody, Exhibits Preclinical Efficacy in Models of Hematological Malignancies (ASH 2022) - P1/2 | "Notably, the combination of LYT-200 and methotrexate treatments led to the best survival outcomes in both contexts. Similar results were obtained in xenograft studies of AML, where single-agent LYT-200 (1.5 mg/kg/weekly) treatment was more effective at protecting mice than cytarabine (100 mg/kg/weekly). However, combining both treatments resulted in the best survival outcomes with greater than 80% of mice surviving over 2 months after disease appearance. In all, our results demonstrate that GAL-9 is an important driver of multiple blood cancer subtypes and that targeting GAL-9 with LYT-200 represents a potential novel treatment strategy which warrants additional pre-clinical and clinical testing."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • Transplantation • HAVCR2 • LGALS9 • PD-1

LYT-200 Alone and in Combination With Chemotherapy or Tislelizumab in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: PureTech | N=250 ➔ 80 | Trial completion date: Dec 2022 ➔ Sep 2024 | Trial primary completion date: Dec 2022 ➔ Mar 2024

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

PureTech Provides End of Year Report on Key Progress (Businesswire) - "Based on these and other compelling preclinical data generated with LYT-200 in blood cancers, PureTech initiated a clinical trial to evaluate LYT-200 as a single agent for the treatment of AML, with results expected in 2023....Given the expansion of the clinical evaluation of LYT-200, the Company has deprioritized preclinical development of LYT-210."

Clinical data • Pipeline update • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

PureTech Presents Data for LYT-200 Targeting Galectin-9 in Preclinical Leukemia Cancer Models at the 64th American Society of Hematology (ASH) Annual Meeting (Businesswire) - "The ASH poster evaluates galectin-9 expression and the effects of LYT-200 in multiple types of leukemia....In all models used, LYT-200 demonstrated significant anti-tumor activity and in addition to its established effects on the immune system in solid tumor models, it also notably induced direct apoptosis or cell death across all leukemia cell types. In a model assessing DNA damage in AML cells, LYT-200 significantly outperformed an anti-TIM3 antibody....PureTech has initiated a clinical trial to evaluate LYT-200 as a single agent for the treatment of AML with results expected in 2023....The combination part of the Phase 1 trial in certain metastatic solid tumors with LYT-200 in combination with tislelizumab is expected to begin in the first quarter of 2023."

Clinical data • Preclinical • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Phase1/2 study of an anti-galectin-9 antibody, LYT-200, in Patients With Metastatic Solid Tumors (SITC 2021) - P1/2 | "Phase 2 expansion cohorts would implement the Simon’s two-stage design to further assess LYT-200 as a single agent and/or in combination with chemotherapy and tislelizumab. Phase 2 is currently planned in pancreatic cancer and other/different tumor types for Phase 2 may be guided by results of the Phase 1. Trial Registration NCT04666688"

Clinical • IO biomarker • P1/2 data • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor