LYT-200

Hematological malignancies, such as acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), and locally advanced/metastatic solid tumors, including head and neck cancers

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Hematological malignancies, such as acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), and locally advanced/metastatic solid tumors, including head and neck cancers

100% Equity

Phase 1/2

Description

Hematological malignancies, such as acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), and locally advanced/metastatic solid tumors, including head and neck cancers

Puretech Ownership¹

100% Equity

Stage of Development

Phase 1/2

¹ We have an active IND on file with the FDA for LYT-200. The FDA and corresponding regulatory authorities will ultimately review our clinical results and determine whether our wholly-owned therapeutic candidates are safe and effective. No regulatory agency has made any such determination that LYT-200 is safe or effective for use by the general public for any indication.

Hematological malignancies, such as acute myeloid leukemia and high-risk myelodysplastic syndrome, and locally advanced/metastatic solid tumors, including head and neck cancers

Gallop Oncology™ is advancing a first-in-class, mechanistically differentiated approach to cancer treatment by targeting a novel, pro-tumor and immunosuppressive molecule. Gallop’s LYT-200 is an anti-galectin-9 monoclonal antibody (mAb) being developed for the treatment of hematological malignancies, including acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), as well as solid tumors, including head and neck cancers, with a focus on metastatic disease.

Program Discovery Process by the PureTech Team
- With a focus on providing significant therapeutic benefit to cancer patients, we opportunistically identified a foundational immunosuppressive/pro-tumor mechanism(s) involving galectin-9, which was the basis of certain intellectual property that we licensed from New York University prior to its publication in Nature Galectin-9 promotes multiple immunosuppressive pathways in the context of solid tumors and blocking galectin-9 results in tumor cell death in the context of AML and other hematological malignancies. High levels of galectin-9 expression in tumor tissue, on leukemia cells as well as in patients’ blood are linked to more advanced disease and worse outcomes. LYT-200 is a fully human IgG4 monoclonal antibody designed to inhibit the activity of galectin-9. We believe that LYT-200 is the most advanced clinical program against this target. It has the potential to be used as a single agent and in combination with other anti-cancer therapies, depending on the cancer type, treatment setting, and line of treatment. In pre-clinical models, LYT-200 has also demonstrated direct cytotoxic, anti-leukemic effects through multiple mechanisms, as well as synergy with standard of care.
Patient Need & Market Potential
- AML
  - The National Cancer Institute estimates that about 60,000 new cases of leukemia are diagnosed each year,² including about 20,000 in AML.³ More than 50% of AML patients either don’t respond to initial treatment or experience relapse or death after responding to initial treatment⁴ and a median survival time of less than six months.⁵ The poor overall survival highlights the need for more effective therapies for patients with relapsed and refractory AML.
- Metastatic/locally advanced solid tumors
  - In the US, there are approximately 82,000 new cases of bladder cancer each year⁶
  - In the US, there are approximately 66,000 people diagnosed with head and neck cancers each year.⁷ At diagnosis, ~10% of patients have metastatic disease though an additional 20-30% will develop metastases during the course of their disease. The prognosis for metastatic disease is unfavorable with a median survival of about 10 months.⁸
Milestones Achieved & Development Status
- AML
  - The Phase 1b trial evaluating LYT-200 as a monotherapy and in combination with venetoclax/ HMA for AML and MDS is ongoing. LYT-200 has shown a favorable safety profile across both arms and all dose levels with no dose limiting toxicities, as well as clinical efficacy, hematological improvement, and sustained disease management.
    - As of April 28, 2025, patients have received LYT-200 at five dose levels (2.0 mg/kg to 16.0 mg/ kg) in the monotherapy arm. Across all dose levels, LYT-200 has demonstrated 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. At dose levels of 7.5mg/kg and above, treatment with LYT-200 has resulted in 1 complete response (CR), 3 partial responses (PRs), and more than 50% of patients treated experienced stable disease. The average treatment duration with the single agent was 3.5 months as of the data cutoff. This is meaningful in the heavily pretreated patient population who have already exhausted all standard-of-care options.
    - When administered in combination with venetoclax/hypomethylating agents (HMA), results as of April 28, 2025, 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, 7.5 mg/kg, and 12.0 mg/kg) with venetoclax/ HMA, resulting in 6 CRs, 1 morphological leukemia-free state (MLFS), and 50% of patients experienced stable disease. The average time on combination therapy is 4 months as of the data cutoff, which is meaningful in a patient population whose time to progression tends to be less than 1 month and whose overall survival averages 1.7-2.4 months with standard-of- care therapy. Patients who benefit show hematological improvement as well as achieve transfusion independence.
  - In January 2025, we anounced that the FDA has granted Fast Track designation to LYT-200 for the treatment of AML. Fast Track designation is a process designed to streamline the development and accelerate the assessment of drugs that target serious conditions with unmet medical need. The FDA has also granted orphan drug designation to LYT-200 for the treatment of AML.
  - In December 2024, we presented data from the dose escalation phase of the Phase 1b trial evaluating LYT-200 in patients with relapsed or refractory acute AML and MDS at the 2024 American Society of Hematology (ASH) Annual Meeting. 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. 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. 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.
  - In February 2024, the FDA granted Orphan Drug Designation to LYT-200 for the treatment of AML. The FDA grants orphan drug designation to novel drug and biologic products for the treatment, diagnosis, or prevention of conditions affecting fewer than 200,000 persons in the U.S. Orphan drug designation qualifies PureTech for incentives under the Orphan Drug Act, including tax credits for some clinical trials and eligibility for seven years of market exclusivity in the U.S., if the drug is approved for AML.
  - In December 2023, we announced in the ongoing Phase 1b trial evaluating LYT-200 as a single agent in relapsed/refractory AML and MDS patients, three dose escalation cohorts have completed to date at weekly doses of 2 mg/kg (cohort 1), 4 mg/kg (cohort 2) and 7.5 mg/kg (cohort 3). In a heavily pre-treated patient population, the early data demonstrates a favorable safety and tolerability profile of LYT-200 with no dose limiting toxicities. In the first cohort, disease stabilization was observed in two of the five patients treated, with one patient achieving red blood cell transfusion independence. In the second cohort, disease stabilization was observed in two of the four patients treated. In the third cohort, disease stabilization was observed in all four of the patients treated, with a reduction in bone marrow blasts observed in two of the four patients and the clearance of peripheral blasts observed in one patient. Two patients achieved more than 50 percent bone marrow blast reduction, with one of these patients observing an increase in platelet count without transfusions. The fourth cohort, evaluating a weekly regimen of LYT-200 at the 12 mg/kg dose, is still ongoing, and additional data are expected to be shared in a scientific forum.
  - In December 2022, a poster describing new preclinical data supporting the clinical potential of LYT-200 for the treatment of leukemia was presented at the American Society of Hematology (ASH) 64th Annual Meeting. 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. Based on this and other compelling preclinical data generated with LYT-200 in blood cancers, we initiated a clinical trial to evaluate LYT-200 as a single agent for the treatment of AML.
- Metastatic/locally advanced solid tumors
  - 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, has successfully completed. LYT-200 demonstrated a favorable safety profile in all cohorts and showed disease control and initial efficacy signals. The LYT-200 solid tumor study enrolled 44 relapsed/refractory solid tumor patients across 13 sites in the United States.
    - The single agent (SA) cohorts dosed LYT-200 between 0.2 – 16 mg/kg every two weeks (Q2W) or 10 mg/kg every week (QW). The combination cohorts dosed LYT-200 at 6.3mg/kg QW and 16mg/kg QW with an anti-PD-1 antibody, tislelizumab. The SA cohorts enrolled 20 all-comer patients, while the combination cohorts enrolled 24 patients, including 19 with head and neck cancer and five with urothelial cancer. The median number of prior lines of treatment was four in the single agent cohorts and three in the combination cohorts. There were no dose limiting toxicities in this study. There were no LYT-200 related serious adverse events in the SA cohorts. Eight patients (40%) experienced grade 3 or higher adverse events, none of which were related to LYT-200. In combination with tislelizumab, three patients (12.5%) experienced an immune mediated adverse reaction (IMAR), all of which were related to tislelizumab (grade 2 hypothyroidism, grade 1 hyperthyroidism, and grade 3 cholangitis). There was one LYT-200- related grade 3 serious adverse event, an asymptomatic elevation of the protein troponin, that occurred with 16 mg/kg QW LYT-200 plus tislelizumab, led to treatment discontinuation, but resolved fully on steroid treatment. 14 patients (58.3%) experienced grade 3 or higher adverse events of which one (the elevated troponin) was related to LYT-200. In the SA cohorts, three patients (16% of evaluable patients) achieved stable disease. Disease control has been noted from dose levels of 6.3 mg/kg and above.
    - In the combination cohorts, two urothelial cancer patients (out of 4 evaluable patients) treated with 6.3 mg/kg QW LYT-200 plus tislelizumab had stable disease. In head and neck patients treated with 6.3 mg/kg QW LYT-200 plus tislelizumab, one patient experienced a complete response lasting more than 2 years; two patients had a partial response; and two patients had stable disease, resulting in an overall response rate of 33% and a disease control rate of 50%. At 16 mg/kg plus tislelizumab, three patients (out of seven evaluable) had stable disease, giving a disease control rate of 43%. For patients achieving a response as per RECIST 1.1 criteria, the six-month progression-free survival (PFS) is 67%, and the 12-month PFS is 33%.
  - In March 2024, the FDA granted Fast Track designation for LYT-200 in combination with anti-PD1 therapy for the treatment of recurrent/metastatic head and neck cancers. Fast Track designation is a process designed to streamline the development and accelerate the assessment of drugs that target serious conditions with unmet need.
  - In December 2023, initial data from the Phase 1 portion of the Phase 1/2 dose escalation and expansion clinical trial of LYT-200 was announced. LYT-200 is being evaluated as a monotherapy and in combination with tislelizumab, an anti-PD-1 antibody being developed by BeiGene, in metastatic solid tumors, including head and neck cancers. The initial data, which was presented at the ESMO Immuno-Oncology, demonstrate that LYT-200 has a favorable safety profile in all cohorts, including the monotherapy and combination arms, and shows disease control and suggestion of anti-tumor activity in combination with tislelizumab. In the combination cohort, anti-tumor activity was observed in patients with relapsed or refractory head and neck squamous cell carcinoma, a patient population that has historically demonstrated a low response rate to anti-PD-1 agents of around 20 percent and 10 percent with chemotherapy.⁹
  - In the first quarter of 2023, we initiated a Phase 1b trial of LYT-200 in combination with tislelizumab in head and neck cancers.
  - In December 2022, we announced results from the monotherapy dose escalation portion of the Phase 1 program of LYT-200 as a potential treatment for metastatic solid tumors. No dose-limiting toxicities were reported, and the full results are planned for presentation in a scientific forum in 2023.
Expected Milestones
- The Phase 1b clinical trial evaluating LYT-200 in relapsed/refractory AML and MDS patients is ongoing, as patients are responding well to and remaining on treatment. Topline results are expected in Q3 2025, and patients can elect to remain on treatment.
Intellectual Property
- The intellectual property portfolio for LYT-200 provides broad intellectual property coverage for antibody-based immunotherapy technologies. As of December 31, 2024, there are 16 families of intellectual property within this patent portfolio, including eight (8) families of patent filings that are co-owned with and/or exclusively licensed from New York University which cover antibodies that target galectin-9, including LYT-200, and methods of using these antibodies in various immuno-oncology technologies and other therapeutic methods. In addition, the intellectual property portfolio includes seven (7) families of company-owned patent applications covering the use of anti-galectin-9 antibodies in the diagnosis and treatment of various cancers, including solid tumors and hematological cancers, and one family of patent applications co-owned with BeiGene directed to combination therapies for the treatment of solid tumors. This intellectual property portfolio comprises four (4) issued U.S. patents which are expected to expire in 2038, 14 pending U.S. patent applications, which if issued, are expected to expire 2037 through 2045, one (1) international PCT application, 82 pending foreign applications and 20 issued patents in foreign jurisdictions.

LYT-200 is an investigational drug not approved by any regulatory authority.

² Leukemia – Cancer Stat Facts. (n.d.). National Cancer Institute. https://seer.cancer.gov/statfacts/html/leuks.html.

³ Acute Myeloid Leukemia – Cancer Stat Facts. (n.d.). National Cancer Institute. https://seer.cancer.gov/statfacts/html/amyl.html.

⁴ Walter, R. B., Othus, M., Burnett, A. K., Löwenberg, B., Kantarjian, H. M., Ossenkoppele, G. J., Hills, R. K., Ravandi, F., Pabst, T., Evans, A., Pierce, S., Vekemans, M.,
Appelbaum, F. R., & Estey, E. H. (2015). Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. Leukemia, 29(2), 312–320. https://doi.org/10.1038/leu.2014.242.

⁵ Miyamoto 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.

⁶ Cancer of the Urinary Bladder – Cancer Stat Facts. (n.d.). National Cancer Institute. https://seer.cancer.gov/statfacts/html/urinb.html.

⁷ Head and Neck Cancer – Statistics. (2022, December 16). Cancer.Net. https://www.cancer.net/cancer-types/head-and-neck-cancer/statistics.

⁸ Pisani, P., Airoldi, M., Allais, A., Valletti, P. A., Battista, M., Benazzo, M., Briatore, R., Cacciola, S., Cocuzza, S., Colombo, A., Conti, B., Costanzo, A., Della Vecchia, L., Russi, E. G., Fantozzi, C., Galizia, D., Garzaro, M., Genta, I., Iasi, G. A., . . . Zigliani, A. (2020). Metastatic disease in head & neck oncology. Acta Otorhinolaryngologica Italica, 40(SUPPL. 1), S1–S86. https://doi.org/10.14639/0392-100x-suppl.1-40-2020.

⁹ Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656. PMID: 18784101.

Given its design to inhibit the activity of galectin-9, LYT-200 is being advanced to potentially remove a key immunosuppressive barrier that would enable the immune system to attack and destroy the tumor. Our fully human monoclonal antibody candidate has potential both as a single agent and in combination with existing therapies such as checkpoint inhibitors and chemotherapeutics.