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Lyell Presents Positive Initial Clinical Data from the Phase 1-2 Clinical Trial of IMPT-314 for the Treatment of B-cell Lymphoma at the 2024 ASH Annual Meeting

On December 9, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with solid tumors or hematologic malignancies, reported initial positive clinical data from the multi-center Phase 1-2 study of IMPT-314 in patients with large B-cell lymphoma that is being presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Lyell Immunopharma, DEC 10, 2024, View Source [SID1234648922]). IMPT-314 is an autologous dual-targeting CD19/CD20 chimeric antigen receptor (CAR) T-cell product candidate being developed for patients with aggressive B-cell non-Hodgkin lymphoma.

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As of October 22, 2024 (the data cutoff for the presentation), 23 patients with relapsed or refractory (R/R), CAR T-naive large B-cell lymphoma received IMPT-314. The efficacy evaluable population consisted of 17 patients. The ORR was 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were in response at last follow-up). In the safety evaluable population of 23 patients, no Grade 3+ CRS was reported. Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy. In the efficacy evaluable set, 16 patients were evaluable for pharmacokinetics. IMPT-314 demonstrated robust expansion and peak cell expansion occurred between Days 7 – 28 post IMPT-314 infusion (median Tmax = 10 days). Additionally, the final drug product contained the desired naïve and central memory cell phenotype (median, 91%; range, 82 – 99%) that has been associated with improved overall survival in other CAR T cell clinical studies.

The data are being presented today at the 2024 ASH (Free ASH Whitepaper) Annual Meeting by Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, and the poster is available in the Investors’ section of the Company’s website.

"The high rate of complete responses with a favorable safety profile support the strong potential of IMPT-314, Lyell’s next-generation dual-targeting CAR T-cell therapy enriched for naïve and central memory T cells. This product candidate was designed to maximize durable responses by overcoming heterogeneous CD19 antigen density and antigen escape, enhance CAR T cell persistence, and reduce exhaustion," said Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. "Based on these strong data, we remain on track to initiate a pivotal trial in 2025 of IMPT-314 in CAR T-naive patients with large B-cell lymphoma in the 3rd-line+ setting and are continuing to evaluate IMPT-314 in the 2nd-line setting in the ongoing Phase 1-2 trial."

"The data presented today from IMPT-314 suggest the potent targeting of both CD19 and CD20 coupled with CD62L+ cell enrichment has the potential to provide differentiated benefit in objective and complete response rates over first-generation CD19 CAR therapies in patients with aggressive large B-cell lymphoma," stated Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA. "IMPT-314 incorporates the same CAR construct as CART19/20 which was evaluated in a Phase 1 trial at UCLA, and I am pleased that the IMPT-314 data are consistent with our experience at UCLA."

About IMPT-314

IMPT-314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the response as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.

IMPT-314 is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both. IMPT-314 is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity.

IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory aggressive B-cell lymphoma.

GlyTherix and Nusano Announce Alpha and Beta Isotope Supply Agreement

On December 9, 2024 GlyTherix and Nusano, a physics company transforming the production of radioisotopes, reported a supply agreement for non-carrier-added lutetium-177 (Lu-177) (Press release, Glytherix, DEC 10, 2024, View Source [SID1234648902]). The agreement also provides GlyTherix access to Nusano’s future actinium-225 (Ac-225) production, currently scheduled to begin in 2026, and planned future production of zirconium-89 (Zr-89), lead-212 (Pb-212) and terbium-161 (Tb-161).

GlyTherix’s radiotherapy approach combines Lu-177 with an antibody targeting Glypican-1, a protein found in aggressive cancers, to deliver localized radiation while sparing healthy tissue.

Glypican-1 is an attractive tumor target that occurs in several aggressive and invasive cancers including prostate, pancreatic, bladder, lung, glioblastoma, esophageal and ovarian cancer. GlyTherix plans to use 177Lu-DOTAMiltuximab in its planned Australian Phase Ib in 2025, followed by US Phase II trials in 2026.

Cimeio Therapeutics Announces Partnership with Kyowa Kirin to Develop Novel Cell Therapies

On December 9, 2024 Cimeio Therapeutics reported that it has entered a research collaboration with Kyowa Kirin Co., Ltd. (Kyowa Kirin) to develop a novel therapy for diseases with high unmet need (Press release, Cimeio Therapeutics, DEC 10, 2024, View Source [SID1234648894]).

The partnership combines Cimeio’s proprietary Shielded Cell and Immunotherapy (SCIP) platform with Kyowa Kirin’s expertise in cellular therapies and underscores both companies’ commitment to using emerging cell and gene therapy technologies to develop new ways to treat patients. Under the terms of the agreement, Cimeio is eligible to receive an upfront payment and two years of research funding. Upon Kyowa Kirin’s exercise of a commercial license option, Cimeio will be eligible for development and commercial milestones as well as royalties on sales of potential products arising from the partnership. Further terms are not disclosed.

Cimeio’s SCIP platform is based on the development of novel immunotherapies enabled by epitope-shielded cells. These cells contain modified variants of naturally occurring cell surface proteins that maintain their function but are resistant to depletion by the paired immunotherapy. These shielded cells enable the development of powerful therapeutics for previously undruggable targets, targeted conditioning for HSC transplant, and immune system reset amongst other applications.

"We are thrilled to collaborate with Kyowa Kirin, a company with a rich history of investing in innovative technologies that have the potential to significantly improve outcomes for patients with serious conditions," said Dr. Stefanie Urlinger CSO of Cimeio. "This partnership represents a significant step forward for our company and mission."

"Kyowa Kirin and Cimeio share the vision for the potential of therapeutics enabled by epitope-shielded cells," said Yoshifumi Torii, Ph.D, Executive Officer, Senior Vice President, Head of Research Division of Kyowa Kirin. "With this partnership we believe we can develop a safe and effective therapy for diseases that in the past have been incredibly difficult to treat, and we’re looking forward to working with the talented team at Cimeio."

Olema Oncology Announces FDA Clearance of Investigational New Drug Application for OP-3136, a Potent KAT6 Inhibitor

On December 9, 2024 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for OP-3136, a novel small molecule that potently and selectively inhibits KAT6, a validated epigenetic target that is dysregulated in breast and other cancers (Press release, Olema Oncology, DEC 9, 2024, View Source [SID1234649036]).

"We are very pleased to have received notification from the FDA that OP-3136 may proceed into the clinic," said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. "The compelling activity demonstrated by OP-3136 in preclinical models both as a single agent and in combination with palazestrant has generated strong investigator interest in OP-3136. We expect to initiate the Phase 1 clinical trial early next year and are excited by OP-3136’s potential in breast cancer and beyond."

TScan Therapeutics to Present Updated Data from the Ongoing ALLOHA™ Phase 1 Heme Trial During Oral Session at the 66th American Society of Hematology Annual Meeting and Exposition

On December 9, 2024 TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biotechnology company focused on the development of T cell receptor (TCR)-engineered T cell (TCR-T) therapies for the treatment of patients with cancer, reported that updated results from the ongoing ALLOHA Phase 1 trial of TSC-100 and TSC-101 will be presented during an oral session at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, TScan Therapeutics, DEC 9, 2024, View Source [SID1234648995]). TSC-100 and TSC-101 are designed to treat residual disease and prevent relapse in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT) with reduced intensity conditioning.

"Disease relapse is the leading cause of death in patients undergoing transplant following reduced intensity conditioning and represents a significant unmet medical need," said Chrystal U. Louis, M.D., Chief Medical Officer. "As the majority of patients enrolled in both the treatment and control arms were considered at very high risk for relapse, we are highly encouraged by the preliminary ALLOHA study results, which suggest that TSC-100 and TSC-101 have the potential to eliminate residual disease and prevent relapse in patients with AML, ALL, or MDS post-HCT."

"We are very excited by these data and, based on these results, we intend to launch a pivotal trial in the second half of 2025," said Gavin MacBeath, Ph.D., Chief Executive Officer. "Following recent feedback from the FDA, we believe we have a clear development path and will share our plans at our KOL event tomorrow morning."

In the ongoing ALLOHA Phase 1 trial (NCT05473910), patients receive either TSC-100 or TSC-101 post-HCT, whereas control-arm patients receive HCT alone as per standard of care. To date, 38 patients have been enrolled in the trial and undergone HCT, with 26 in the treatment arm and 12 in the control arm. The key endpoints in the trial are safety and efficacy, with exploratory endpoints including donor chimerism and minimal residual disease (MRD) status.

Key Presentation Highlights:

To date, event-free survival strongly favors the treatment arm (HR=0.30; p=0.04) and early trends suggest a lower probability of relapse (HR=0.28; p=0.14).
2 of 26 (8%) treatment-arm patients relapsed compared to 4 of 12 (33%) control-arm patients. One treatment-arm relapse and subsequent mortality occurred in a very high-risk patient who was taken to transplant without first achieving complete remission, and the other was an extramedullary relapse in the patient’s central nervous system with no evidence of systemic relapse.
Median time to relapse was not evaluable in the treatment arm versus 160 days in the control arm.
8 of 38 (21%) patients in the study had TP53 mutations, with 6 cases in the treatment arm and 2 cases in the control arm. Of the 4 patients in the treatment arm with these mutations who received TCR-T cell infusions, none has relapsed, and one patient has now been relapse-free for 22 months. Of the 2 patients in the control arm with mutated TP53, both relapsed within 6 months of transplant and died shortly thereafter.
TSC-100 and TSC-101 infusions were well-tolerated at all three dose levels with no dose-limiting toxicities. Observed adverse events were similar across the treatment and control arms and were generally consistent with post-HCT adverse events.
TSC-100 and TSC-101 TCR-T cells were detected at all timepoints in all treated patients, including those who have been on study for over a year, with clear evidence of a dose-persistence relationship.
A copy of the presentation materials will be made available on the "Publications" section of the Company’s website at tscan.com once the presentation has concluded.

Virtual Key Opinion Leader (KOL) Event

The Company will host a virtual KOL event featuring Ran Reshef, M.D., M.Sc., on Tuesday, December 10, 2024, at 8:00 a.m. ET to discuss the data presented at ASH (Free ASH Whitepaper), updates with regards to a potential registrational path for the program following its initial meeting with the U.S. Food and Drug Administration, as well as future plans to expand the program, in addition to an update on the Company’s PLEXI-T Phase 1 solid tumor trial.

Dr. Reshef is the Professor of Medicine and Director of the Cellular Immunotherapy Program at Columbia University Irving Medical Center. Details for attending the event can be found here.