The treatment landscape for acute myeloid leukemia (AML), particularly in the relapsed or refractory (R/R) setting, remains a stark portrait of unmet need. For patients who exhaust frontline therapies, including the standard venetoclax/hypomethylating agent (VEN/HMA) combination, options dwindle rapidly, and outcomes are grim, with median overall survival (OS) often measured in just months.

This desperate backdrop makes the emergence of any signal of durable efficacy and tolerability a significant event. At the 2025 American Society of Hematology (ASH) Annual Meeting, one such signal commanded attention. Gallop Oncology, a subsidiary of PureTech Health, revealed Phase Ib results for LYT-200, a first-in-class anti-galectin-9 monoclonal antibody, demonstrating survival figures that defy current expectations in this underserved patient population.

The data show a median overall survival (mOS) of 13.2 months for heavily pre-treated patients receiving LYT-200 combined with VEN/HMA at the proposed Phase 2 dose. This represents a dramatic improvement over the 1.7 to 2.4-month survival typical with later-line standard of care.

To understand the implications of these findings, the mechanism behind them, and the path forward, Drug and Device World spoke with two key leaders from Gallop: CEO Luba Greenwood and Chief Medical Officer Dr. Aleksandra Filipovic. They delve into the science of targeting galectin-9, the striking efficacy and safety signals, and their vision for transforming AML therapy.

A Foundational Target

The compelling clinical data for LYT-200, as Dr. Filipovic emphasized in our conversation, begins with a deliberate choice of galectin-9 as a novel target. “[It has high relevance] very broadly in AML and a very unique as well as differentiated mode of action,” she stated.

The ASH poster frames gal-9 as a “foundational driver of leukemia,” crucial for disease development, progression, and treatment resistance through both direct oncogenic signaling and systemic immunosuppression. Critically, it is overexpressed on AML stem cells but not on normal hematopoietic stem cells, creating a potential therapeutic window.

Dr. Filipovic explained the target’s pivotal role as a “governing factor both oncogenically and at the level of immune suppression as well as sustaining the microenvironment in AML… [It] sits at the top of the hierarchy of perhaps other downstream pathways.” This foundational biology, she argues, is why LYT-200 shows such strong signals early in development. Luba Greenwood contrasted this with mutation-specific approaches: AML is biologically complex so targeting one mutation at a time doesn’t address the core disease, she said. “Patients] have been on mutation-specific drugs… And then they all relapse right within a few years. And then for that, there’s really nothing.”

Unprecedented Survival Signals in a Phase I Trial

The core of the excitement at ASH lies in the survival data from this Phase Ib dose-escalation/expansion study (NCT05829226). The trial enrolled heavily pre-treated patients with R/R AML or high-risk MDS, with a median of three prior lines of therapy. In the combination arm, 87.5% were pre-treated with VEN/HMA.

The results were striking. As a single agent across all dose levels, LYT-200 achieved an mOS of 6.5 months in all efficacy-evaluable patients (n=26), a mark that already matches the reported mOS of recently approved menin inhibitors in earlier-line, targeted populations.

However, the combination data with VEN/HMA is what breaks the paradigm. The poster reports an initial mOS of 13.2 months for efficacy-evaluable patients at the proposed Phase 2 dose of 12 mg/kg (n=32). Dr. Filipovic contextualized this: “We get into the combination setting with VEN/HMA where the survival… is much higher at 13.2 months and counting mind you, because we haven’t yet completed the overall survival follow-up.” She directly contrasted this with the historical benchmark: “Initial survival exceeds 1.7 – 2.4-month window typical with SOC.”

This survival benefit was accompanied by robust response rates. At the 12 mg/kg dose, the combined complete response (cCR) rate was 38%, with an overall response rate (ORR) of 50% and a disease control rate (DCR) of 97%. Furthermore, the therapy enabled a bridge to transplant for over 50% of patients who achieved a complete response, a critical metric in this setting.

The Critical Importance of a Clean Safety Profile

In AML, especially in the frail, late-line population, efficacy without tolerability is a hollow victory. Both Greenwood and Dr. Filipovic, along with the poster data, stress that LYT-200’s safety profile may be as transformative as its efficacy. “The safety profile is truly critical. We not only want the patients to respond, we also want them to live well for long,” said Dr. Filipovic.

The poster confirms an “exceptionally clean safety profile”. Notably, there were no dose-limiting toxicities or serious adverse events (SAEs) related to LYT-200 observed in either single-agent or combination cohorts. No infusion-related reactions were reported, and no premedication is required. Dr. Filipovic attributed this directly to the target biology: Galectin 9 is not expressed or has very low levels of expression within the normal hematopoietic stem cell, she said. “For that reason, this compound has no hematological toxicities.”

This absence of overlapping myelosuppression is crucial for combination therapy. Dr. Filipovic explained, “There lies the differentiating hypothesis and proof that we are not overlapping with venetoclax HMA predominant toxicity pattern. There is no additional toxicity. There’s actually even a benefit that LYT-200 is creating, allowing for VEN/HMA to actually be dosed for longer.”

 The poster’s summary of treatment-emergent adverse events (TEAEs) supports this, showing that the profile in the combination arm is consistent with known VEN/HMA toxicities like anemia, febrile neutropenia, and pneumonia, with no new safety signal added by LYT-200.

Greenwood relayed feedback from investigators: “[They] are calling us to say how well the patients feel on LYT-200.” This tolerability enables long-term dosing, which appears linked to durable responses. Dr. Filipovic noted that one single-agent patient has been on treatment for 27 months as of November 2025.

A Dual “Two-Gear” Mechanism of Action

The clinical profile of LYT-200 is designed around its unique mechanism, described by Dr. Filipovic as a “a two-gear approach.” Gear one involves direct anti-tumor killing. “This is why we see fast responses and deep responses in patients. And these happen quickly after 1, 2, 3 cycles of treatment,” she said.

Gear two involves immune system reactivation. “The durability of response manifested in such a long overall survival is a testament to… the immunomodulatory potential of the drug because the patients are doing so well,” she added. The antibody blocks a unique gal-9 epitope to neutralize its signaling, which in the tumor microenvironment suppresses T and NK cell activity. By reversing this suppression, LYT-200 may help sustain long-term disease control.

Biomarker analyses presented in the poster provide early mechanistic support. NanoString gene array analyses on patient samples identified pathways associated with response, including DNA damage, apoptosis, and immunity. On the importance of biomarker strategies, Dr. Filipovic noted that these data have allowed Gallop to “both understand and confirm in the clinical context the mechanism of action. We’ve disclosed some of that on the poster… [which] confirms that the mode of action which we have seen preclinically… is exactly what we observe in patients.”

Addressing Broad Unmet Needs and Future Directions

When asked about the broader unmet needs in AML, Dr. Filipovic outlined several that LYT-200 appears to address: safety/combinability, potential for long-term maintenance therapy, and activity across AML subtypes regardless of mutation. “This compound isn’t limited to any one subgroup of patients… The signal is equal across primary AML, secondary AML… complex cytogenetics, high risk clinically, and the efficacy and the safety hold,” she stated.

The future development path is being shaped by this early success. The program was awarded Fast Track designation by the US Food and Drug Administration (FDA) in December 2024. The formal guidance on the Phase II trial initiation is expected to follow final OS data in the first half of 2026, and regulatory discussions.

Dr. Filipovic indicated that the Fast Track designation acknowledges the potential “to be further explored in development across lines of treatment in both the single agent and the combination context.” The logical progression is into earlier lines of therapy. Greenwood framed the ambition broadly: “For us, we see [LYT-200] as a step in how we treat not just relapse refractory [but to also] go frontline, go maintenance and there just hasn’t been anything, anything like that.”

Furthermore, the potential extends beyond AML. The drug was initially explored in solid tumors, and its foundational mechanism suggests utility in other hematological malignancies. Greenwood concluded, “It’s not only key and broadly applicable to AML, but it’s also broadly applicable just in hematology period.”

A Potential Paradigm Shift

The presentation of LYT-200 at ASH 2025 offers a rare combination in oncology drug development: a novel, foundational biological target yielding both profound efficacy and exceptional tolerability in one of the most challenging clinical settings. The 13.2-month median overall survival in late-line R/R AML is a figure that commands attention, as it multiplies the expected survival time for these patients.

As summarized in the poster’s conclusion, LYT-200 delivers “robust, durable efficacy,” a “striking survival benefit,” and an “exceptionally clean safety profile” that together can “transform clinical trajectory”.

While larger, registrational studies are the necessary next step, the Phase Ib data for LYT-200 has undeniably set a new benchmark. It provides a compelling answer to the plea from key opinion leaders, which Dr. Filipovic relayed: “We need a drug that can actually be given.”