공시 • Jan 09
Marker Therapeutics Announces Clinical Program Updates and Pipeline Prioritization
Marker Therapeutics, Inc. announced a restructuring of its clinical programs and a strategic prioritization of its multi-tumor associated antigen (multiTAA)-specific T cell product pipeline. In addition, the Company reported a clinical update on the Phase 2 ARTEMIS study investigating MT-401, a multiTAA-specific T cell product, for the treatment of patients with acute myeloid leukemia (AML).Following the non-dilutive transaction with Cell Ready (Press Release, May 1, 2023), Marker has made significant progress on clinical and corporate restructuring with the objective of accelerating the commercial development of their unique multiTAA technology. The Company announced the prioritization of MT-601 in chimeric antigen receptor (CAR) relapse patients with lymphoma (APOLLO; clinicaltrials.gov identifier: NCT05798897). This strategic decision was made based on 1) the Company’s promising non-clinical and clinical data using the multiTAA technology in lymphoma, and 2) the lack of an approved treatment for patients who experience relapse after treatment with CD19 CAR T (up to 60% within a year; Chong EA et al, N Engl J Med, 2021), which is a clear unmet medical need and provides an opportunity for accelerated product development. Highlights from the Lymphoma Study: Clinical Efficacy in Patients with Lymphoma in Previous Clinical Trial: The multiTAA-specific T cell product targeting 5 TAAs was investigated in the TACTAL study, a Phase 1 trial conducted at Baylor College of Medicine. The TACTAL study enrolled patients with Hodgkin’s and non-Hodgkin’s lymphoma and demonstrated clinical safety and efficacy with durable clinical responses for 6 years.Non-Clinical Proof-of-Concept Data: Marker developed a long-term in vitro killing assay 1) to better understand resistance mechanisms following CAR T cell treatment and 2) to determine if a product that is capable of targeting 6 TAAs (MT-601) will be able to kill CAR-resistant lymphoma cells. After CD19-targeting CAR T cell treatment, 98% of lymphoma cells were eliminated in vitro. Long-term follow-up (three weeks) demonstrated outgrowth of CD19-negative tumor cells. Additional anti-CD19 CAR T cell treatment failed to inhibit tumor growth due to the lack of target antigen (CD19) expression on the tumor. Treating CAR-resistant lymphoma cells with MT-601 resulted in complete long-term growth inhibition (over three weeks) highlighting that MT-601 has the potential to effectively treat CD19 CAR-resistant tumors. Durable Response in CAR Relapsed Patient with Lymphoma: The Company-sponsored Phase 1 APOLLO study investigates the safety and efficacy of MT-601 in patients with lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell therapy. The first study participant, a 57-year-old female with diffuse large B cell lymphoma (DLBCL), was enrolled in the Phase 1 dose escalation stage of the trial after failing 4 prior lines of therapy, including anti-CD19 CAR T cell therapy. The participant relapsed within 90 days of CAR T cell therapy, and was treated with MT-601 without prior lymphodepletion. The patient tolerated MT-601 well without treatment-related adverse events and achieved a complete response eight weeks after the second infusion of MT-601. Six months following treatment with MT-601 the study participant has maintained a complete response to treatment suggesting that MT-601 is more durable compared to CAR T cells in this study participant . CD19-targeting CAR T cell therapies are associated with severe side effects and toxicities, and up to 60% of patients with DLBCL relapse within a year (Chong EA et al, N Engl J Med, 2021). Additionally, the FDA is investigating CAR T therapies for the potential risk of inducing secondary cancers (U.S. Food and Drug Administration, Nov. 28, 2023). To date, multiTAA-specific T cell therapies have been well-tolerated in over 200 patients in clinical trials, and Marker believes that, unlike CAR T cells, multiTAA-specific T cells could represent a safer therapeutic option due to their non-genetically engineered approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood without the risk of mutagenesis. Promising Clinical Observations and New Directions with MT-401 in Patients with MRD in AML: Marker is providing a clinical update on the Phase 2 ARTEMIS clinical study (clinicaltrials.gov identifier: NCT04511130), and the direction it will pursue. This multicenter study is evaluating the safety and efficacy of MT-401 in patients with AML after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 8 patients with MRD+ AML after HSCT were enrolled and treated with MT-401. None of the 8 treated patients experienced a drug related adverse event. Of the 8 treated patients, 4 experienced a clinical benefit, with 3 showing a conversion to MRD-negative, and one patient showing a partial response with a logarithmic reduction of MRD levels by PCR. One patient has not yet had the first assessment post treatment. Of the 8 treated patients in the study, only 1 patient had documented disease progression and was taken to a second transplant. The other 3 patients were taken off the study for reasons unrelated to the clinical outcome. Obtaining timely consent and re-accessing HSCT donors for apheresis for the manufacture of MT-401 caused delayed patient accrual and patient eligibility issues. Consequently, the rapid progression of disease contributed to some patients to withdraw from the study prior to administration of study product. Therefore, to streamline resources and to reduce time to treatment, Marker intends to focus on a ready for use product from commercially available leukapheresis material and will discontinue the patient-specific part (ARTEMIS) of the AML program. The Company previously announced that the FDA has cleared the clinical protocol to investigate a ready for use MT-401 product manufactured from healthy donors in patients with AML, and a cellular inventory has been established with continuous efforts to expand this inventory. Marker has secured non-dilutive funding to support the clinical investigation of a ready for use MT-401 product in patients with AML. Using these allocated funds will allow the Company to proceed with the ready for use program without affecting the ongoing Phase 1 APOLLO study and the capital runway of the Company into the fourth quarter of 2025. In addition, the Company has an Investigational New Drug (IND) application cleared by the U.S. FDA for a Phase 1 trial to investigate MT-601 in patients with pancreatic cancer in combination with first-line chemotherapy. The clinical advancement of this multicenter study will be pending additional funding from non-dilutive sources, including grant activities.