PureTech Reports Positive Phase 1b Topline Data for LYT-200 in Relapsed/Refractory High-Risk MDS and AML
PureTech Health plc, a hub-and-spoke biotherapeutics company focused on transforming scientific innovation into value and advancing novel therapies across a range of serious diseases, has announced encouraging topline results from its completed Phase 1b clinical trial evaluating LYT-200. The investigational therapy is a first-in-class, fully human monoclonal antibody targeting galectin-9, a protein implicated in immune evasion and disease progression in multiple hematologic malignancies.
The study evaluated LYT-200 in heavily pretreated patients with relapsed or refractory (R/R) high-risk myelodysplastic syndrome (HR-MDS) and relapsed or refractory acute myeloid leukemia (AML), two aggressive blood cancers associated with poor prognosis and limited treatment options. Based on the positive findings, PureTech’s Founded Entity, Gallop Oncology, has selected a recommended Phase 2 dose (RP2D) and plans to engage with the U.S. Food and Drug Administration (FDA) to discuss a potential next-stage clinical trial design that could ultimately support a registrational pathway in R/R HR-MDS.
A targeted approach in high-unmet-need hematologic cancers
LYT-200 represents a novel immuno-oncology strategy designed to block galectin-9, a molecule increasingly recognized for its role in PureTech suppressing immune responses and enabling tumor survival. By inhibiting this pathway, LYT-200 aims to restore immune activity against malignant cells while also directly impacting tumor biology.
The Phase 1b study (NCT05829226) was conducted across nine clinical sites in the United States and included both monotherapy and combination arms. PureTech The trial enrolled heavily pretreated patients across two distinct but related disease populations: R/R HR-MDS and R/R AML. Patients received LYT-200 alone during dose escalation and subsequently in combination with standard-of-care regimens, including hypomethylating agents (HMAs) such as azacitidine or decitabine, and in AML cohorts, venetoclax (VEN) plus an HMA.
Clinical leadership perspectives on early efficacy and safety
Investigators and company leadership highlighted both the safety profile and early signs of clinical activity as particularly encouraging, especially given the advanced disease status and treatment resistance of the enrolled patients.
“The data from the completed Phase 1b trial highlight the potential for LYT-200 to offer a differentiated treatment approach across a range of myeloid hematological malignancies,” said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech and Chief Medical Officer of Gallop Oncology. “Across patients with R/R HR-MDS and R/R AML, treatment with LYT-200 resulted in deep responses with an exceptionally favorable safety profile. Importantly, the data in R/R HR-MDS were particularly compelling and support prioritizing this indication, especially given the significant unmet need and lack of successful innovation to help these patients.”
She added that the company intends to work closely with regulatory authorities: “We intend to engage with the FDA to discuss the design of a subsequent trial in R/R HR-MDS, as our goal is to accelerate delivery of this promising first-in-class therapy to patients while also laying the foundation for broader clinical development, including in AML.”
Clinical expertise underscores unmet need in MDS
PureTech External clinical experts also emphasized the significance of the findings in high-risk MDS, a disease characterized by bone marrow failure, progression to AML, and limited therapeutic durability.
“The safety profile, combinatorial potential, and level of clinical activity observed with LYT-200 in this Phase 1b study across both R/R HR-MDS and R/R AML is very encouraging,” said Amir T. Fathi, M.D., Program Director of the Center for Leukemia at the Mass General Brigham Cancer Institute and Professor of Medicine at Harvard Medical School. PureTech “In R/R high-risk MDS, where treatment options are extremely limited and outcomes are poor, the findings are particularly notable. The potential to achieve clinical responses without added toxicity would represent a meaningful advance in the MDS treatment landscape and warrants continued clinical development.”
Strategic focus on high-risk MDS development pathway
PureTech leadership also emphasized that the decision to prioritize R/R HR-MDS for further development reflects both the strength of the dataset and the urgent clinical need in this population.
“The results from this Phase 1b trial provide a strong foundation for the next stage of development of LYT-200,” said Eric Elenko, Ph.D., President and Co-founder of PureTech and Acting Chief Executive Officer of Gallop Oncology. “Our decision to prioritize relapsed/refractory high-risk MDS reflects a focused and disciplined approach, grounded in both the data generated to date and the potential to address a tremendous patient need.”
He further noted that regulatory discussions are planned: “We intend to engage with the FDA to discuss a subsequent trial design with the potential to support registration, while continuing to evaluate the broader potential of LYT-200.”
Strong overall safety profile across study population
Across all treated patients in the Phase 1b trial (N=101), LYT-200 demonstrated a consistent and favorable safety profile. Importantly, PureTech there were no dose-limiting toxicities, PureTech no infusion-related reactions, no treatment-related deaths, and no serious adverse events attributed to LYT-200 that led to discontinuation or dose reduction.
The safety profile remained stable across both monotherapy and combination arms, including when administered alongside HMAs or VEN/HMA regimens. Notably, no overlapping or additive toxicities were observed in combination settings, an important consideration for future development in combination-based hematologic cancer therapies.
Six patients at a single study site experienced Grade 3 or 4 hematologic laboratory abnormalities potentially related to LYT-200 in the combination arm at the RP2D dose. These included decreases in platelet counts, white blood cells, and neutrophils. PureTech However, many of these abnormalities were present at baseline or are commonly associated with advanced MDS or AML and existing treatment regimens. No other study sites reported Grade 3 or higher treatment-related adverse events associated with LYT-200.
Encouraging efficacy signals in two difficult-to-treat cancers
The Phase 1b trial also demonstrated meaningful signs of anti-leukemic activity in both disease cohorts, including complete responses, partial responses, and evidence of patients successfully transitioning to stem cell transplantation.
Relapsed/Refractory High-Risk MDS
In efficacy-evaluable patients (n=11) treated at the RP2D (LYT-200 12 mg/kg in combination with an HMA), results included:
- 27.3% complete response rate
- 9.1% partial response rate
- 9.1% marrow complete response rate
- 45.5% overall response rate
- 18% conversion to stem cell transplant
The median overall survival of 6.4 months remains immature, as more than 50% of patients were still alive at study completion.
Patients in this cohort were heavily pretreated, with a median of three prior therapies and universal prior exposure to HMAs. PureTech All patients also presented with high-risk cytogenetics, underscoring aggressive disease biology and poor expected outcomes, further highlighting the potential relevance of LYT-200’s mutation-agnostic mechanism.
Relapsed/Refractory AML
In efficacy-evaluable AML patients (n=26) receiving LYT-200 in combination with VEN/HMA, outcomes included:
- 30.8% composite complete response rate
- 7.7% partial response rate
- 42.3% overall response rate
- 19.2% conversion to stem cell transplant
The median overall survival of 8.2 months remains immature, with more than half of patients alive at data cutoff.
Patients in this cohort had a median of two prior therapies, and the majority (84.6%) had previously received VEN/HMA, indicating significant treatment resistance, including in patients with known venetoclax-resistant mutations.
Pharmacodynamic findings support immune and tumor activity
Early pharmacodynamic analyses provided additional insight into LYT-200’s mechanism of action. Evaluation of peripheral blood mononuclear cells suggested that LYT-200 engages both immune-modulatory and anti-tumor pathways. These findings indicate potential synergistic activity when combined with VEN and HMA therapies.
The data suggest that LYT-200 may enhance immune system activation while simultaneously contributing to direct anti-leukemic effects, a dual mechanism that could be particularly relevant in heavily pretreated hematologic malignancies where immune dysfunction and drug resistance are common.
Overall, the Phase 1b data for LYT-200 support continued clinical development in both R/R HR-MDS and R/R AML, with a strategic emphasis on high-risk MDS due to the strength of early efficacy signals and the significant unmet need in this patient population.
With a favorable safety profile, encouraging response rates in heavily pretreated patients, and early evidence of immune and anti-cancer activity, LYT-200 is emerging as a promising first-in-class galectin-9-targeting therapy.
PureTech Health and Gallop Oncology now plan to engage with the FDA to define a potential registrational pathway, while further evaluating the broader utility of LYT-200 across hematologic malignancies. If confirmed in later-stage trials, the therapy could represent a meaningful advancement for patients with few remaining treatment options.
About Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are a group of serious blood cancers characterized by ineffective blood cell production in the bone marrow, leading to anemia, infections, and bleeding complications.3, 4 MDS affects approximately 60,000–170,000 people in the United States, with an estimated 30–40% of patients diagnosed with the more aggressive form of the disease known as high-risk (HR) MDS.3, 5 HR-MDS is associated with poor outcomes, with median survival typically less than two years following diagnosis, and approximately 30% of patients progressing to acute myeloid leukemia (AML).4-6
The current standard frontline treatment for HR-MDS are hypomethylating agents (HMAs), such as azacitidine and decitabine; however, most patients do not respond to these therapies or eventually stop benefiting from them.7 Once the disease becomes relapsed or refractory (R/R), outcomes are especially poor, with survival often limited to only a few months.7,8
PureTech Treatment options for patients with R/R HR-MDS remain very limited. Only one therapy has been approved specifically for this setting in the past two decades, and it targets only a small subset of patients (~3–5%) with a specific genetic mutation.7 As a result, there remains a significant need for new treatment approaches for patients with HR-MDS.
About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by the rapid growth of abnormal myeloid blast cells in the bone marrow and blood. It is the PureTech most common form of acute leukemia in adults, with a five-year survival rate of less than 30%.9 Despite available therapies, many patients relapse or fail to respond, and outcomes are especially poor in the relapsed/refractory setting. Around 450,000 people globally are living with AML.9
AML is an area of urgent medical need where new therapies with improved safety, efficacy, and durability or responses are critical. Importantly, the incidence of AML is increasing, and the market is expected to grow to $6 billion annually by 2030,10 underscoring the scale of the opportunity to bring forward therapies that are not only more effective but also applicable across a broader segment of patients.
About LYT-200
LYT-200 is a fully human IgG4 monoclonal antibody in development for the treatment of hematological malignancies. LYT-200 targets galectin-9, which is an important oncogenic driver and potent immunosuppressor in cancer, positioning it as a novel target for cancer therapy.11 LYT-200 has been granted Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration (FDA) for the treatment of acute myeloid leukemia.
About Gallop Oncology
Gallop Oncology was founded by and is currently wholly-owned by PureTech Health plc (Nasdaq: PRTC, LSE: PRTC). Gallop is a clinical-stage biopharmaceutical company committed to transforming treatment paradigms for hematologic malignancies. Guided by science and driven to deliver meaningful outcomes for patients, Gallop is advancing a novel approach where efficacy, safety, and durability converge. Its lead candidate, LYT-200, is the most advanced candidate targeting galectin-9, an important oncogenic driver and potent immunosuppressor in cancer, offering a differentiated strategy to address some of the most challenging cancers. For more information, please visit www.galloponcology.com.
About PureTech Health
PureTech Health is a hub-and-spoke biotherapeutics company dedicated to giving life to science and transforming innovation into value. We do this through a proven, capital-efficient R&D model focused on opportunities with validated pharmacology and untapped potential to address significant patient needs. This strategy has produced dozens of therapeutic candidates, including three that have received U.S. FDA approval. By identifying, shaping, and de-risking these high-conviction assets, and scaling them through dedicated structures backed by external capital, we accelerate their path to patients while creating sustainable value for shareholders.
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