On January 9, 2025 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the lives of patients with devastating diseases, reported that the U.S. Food and Drug Administration ("FDA") has granted Fast Track designation to LYT-200, a first-in-class anti-galectin-9 monoclonal antibody, for the treatment of acute myeloid leukemia ("AML") (Press release, PureTech Health, JAN 9, 2025, View Source [SID1234649546]). 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.

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"Fast Track designation from the FDA reinforces our belief in the potential for LYT-200 to address the urgent needs of AML patients," said Luba Greenwood, J.D., Entrepreneur-in-Residence at PureTech who is leading the Gallop Oncology work. "This milestone builds on the FDA’s recognition of LYT-200’s promise, including Orphan Drug designation for AML and a second Fast Track designation for head and neck cancers, both of which were granted last year. By targeting galectin-9, a key driver of cancer proliferation and immune suppression, LYT-200 represents a novel and promising approach for patients in need, and we look forward to the continued development of this program."

LYT-200 exerts its therapeutic effects in AML by killing cancer cells directly via apoptosis and DNA damage as well as reactivating central anti-cancer effectors of the immune system. LYT-200 is the most advanced clinical program against galectin-9 and is being evaluated in two ongoing clinical trials, including:

1. Phase 1/2 clinical trial evaluating LYT-200 as a monotherapy and in combination with venetoclax and hypomethylating agents in hematological malignancies, including AML and high-risk myelodysplastic syndrome (MDS). In this trial, LYT-200 has demonstrated a favorable safety and tolerability profile as well as early signals of clinical activity as single agent and in combination.

2. Phase 1/2 trial in advanced/metastatic solid tumors, including head and neck

cancers. In this trial, LYT-200 is being evaluated as a monotherapy and in combination with tislelizumab, an anti-PD-1 antibody developed by BeiGene. To date, LYT-200 has demonstrated a favorable safety profile in all cohorts, including the monotherapy and combination arms with BeiGene’s tislelizumab, and shown disease control and suggestions of initial anti-tumor activity.

The FDA has also granted orphan drug designation to LYT-200 for the treatment of AML as well as a separate Fast Track designation for the treatment of recurrent/metastatic head and neck squamous cell carcinomas ("head and neck cancers"), in combination with anti-PD1 therapy. PureTech previously announced that it intends to advance LYT-200 via its Founded Entity, Gallop Oncology.

About LYT-200

LYT-200 is a fully human IgG4 monoclonal antibody targeting a foundational oncogenic and immunosuppressive protein, galectin-9, for the potential treatment of hematological malignancies and locally advanced metastatic solid tumors, including head and neck cancers, with otherwise poor survival rates. A wide variety of preclinical data support the potential clinical efficacy of LYT-200 and the importance of galectin-9 as a target and suggest a potential opportunity for biomarker development. PureTech has presented data demonstrating high expression of galectin-9 across various solid tumor types and blood cancers and has found that, in several cancers, galectin-9 levels correlate with shorter time to disease relapse and poor survival. Preclinical work also demonstrates single mechanistic and anti-tumor efficacy of LYT-200 in multiple animal and patient-derived tumor cell models. For example, LYT-200 outperforms anti-PD-1 in solid tumor models models as a single agent. LYT-200 also synergizes with anti-PD-1 in activating CD4 and CD8 T cells in in vivo cancer models. LYT-200 is currently being evaluated in two ongoing Phase 1/2 adaptive design trials for the potential treatment of AML/MDS and head and neck cancers.

On January 9, 2025 Oxford Vacmedix (OVM), the UK-based biopharma company developing vaccines to treat cancer, reported the grant of a prestigious Investor Partnership award from Innovate UK for the clinical development of its lead cancer vaccine OVM-200 (Press release, Oxford Vacmedix, JAN 9, 2025, View Source;utm_medium=rss&utm_campaign=innovate-uk-award-to-ovm-for-clinical-development-of-ovm-200 [SID1234649545]). The award is made as part of the SME Round 6 programme and will contribute to the project costs for Phase 1b for OVM-200. This phase of the trial will enroll a cohort of cancer patients to be treated with an extended dosing protocol newly approved by the UK MHRA (Medicines and Healthcare products Regulatory Agency). The award underpins OVM in attracting inward investment from outside the UK. As previously announced, this has now been achieved with the lead Series B investment from major shareholder Dx&Vx from South Korea, and with additional funding from Prostate Cancer Research. OVM will receive the award over the duration of the project.

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OVM-200 targets survivin, a protein overexpressed by cancer cells that allow unregulated growth, which stimulates an immune response. The vaccine is in a Phase 1 trial in the UK which is both the first time OVM-200 has been used in people and also the first time any ROP (Recombinant Overlapping Peptide) based vaccine has been tested in the clinic. The ongoing trial is focused on safety and on establishing an immune response in advanced cancer patients in three cancer indications: non-small-cell lung cancer (NSCLC), prostate cancer, and ovarian cancer. Initial results from Phase 1a, the dose escalation part of the trial, have shown very good safety and a strong immune response.

Partnership
OVM has a long partnership with Innovate UK and excellent track record of grants, both directly and as part of collaborations. This latest award adds to the support from Innovate UK to develop OVM’s novel groundbreaking ROP technology.

William Finch, CEO of OVM said:

This non-dilutive award from Innovate UK is hugely helpful to fund the ongoing clinical development of OVM-200 and demonstrates real confidence in our ROP technology. We are very pleased with the initial results from Phase 1a and look forward to the completion of this trial to help patients with advanced cancers.

Dr Anthony Coombs, Chairman added:

We are delighted to have this support from Innovate UK for the development of OVM-200 and to be able to incentivise inward investment into the company. The strength of UK technology is regonised worldwide and the recombinant overlapping peptides we are developing have real potential to help patients with cancer, both alone and in combination.

On January 9, 2025 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, reported the advancement of its clinical oncology therapeutic pipeline, and the appointment of Peter J. Tummino, Ph.D., to President of Research and Development (Press release, Nimbus Therapeutics, JAN 9, 2025, View Source [SID1234649544]). Dr. Tummino will be responsible for advancing the company’s product portfolio through all phases of discovery and clinical development.

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The company announced the completion of an investigational new drug (IND) application submission for NDI-219216, a novel Werner syndrome helicase (WRN) inhibitor in development for the treatment of microsatellite instability high (MSI-H) tumors. Nimbus plans to initiate the first clinical trial of NDI-219216 in the first half of 2025 under the leadership of Anita Scheuber, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Oncology.

"We are encouraged by the building momentum in our oncology portfolio including important advances in our non-covalent WRN inhibitor program, with data indicating NDI-219216 has the potential to be a best-in-class agent," said Dr. Tummino.

"NDI-219216 has demonstrated compelling preclinical data, including significant tumor regression and complete responses at low oral doses across tumor types. The preclinical safety studies suggest a promising benefit-risk profile as we prepare to evaluate this compound in patients. We are excited to advance NDI-219216 into a first-in-human clinical trial later this year," said Dr. Scheuber.

The company recently completed its Phase 1/2 clinical study of NDI-101150, a highly selective and potent hematopoietic progenitor kinase 1 (HPK1) inhibitor, for the treatment of advanced solid tumors. Clinical data presented in November 2024 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting demonstrated monotherapy efficacy with a favorable safety profile that supports potential combination therapy approaches. The company is actively evaluating opportunities to maximize the therapeutic potential of this program.

Nimbus continues to progress drug discovery efforts across metabolic and autoimmune targets as well, including the development of novel therapies that activate AMP-activated protein kinase (AMPK) to treat metabolic disorders as part of an ongoing research collaboration and exclusive worldwide license agreement with Eli Lilly and Company. Nimbus has also expanded its pipeline with the addition of new undisclosed therapeutic targets leveraging its novel computational and structure-based drug design approach.

"Nimbus made significant progress in 2024 in our discovery and development programs across oncology, immunology, and metabolism, bringing us one step closer to our ultimate goal of delivering transformative medicines to patients," said Jeb Keiper, M.S., M.B.A., Chief Executive Officer of Nimbus. "Peter’s appointment to President of R&D reflects his exceptional leadership and deep expertise in drug discovery and development, and his expanded role will be instrumental in advancing our innovative pipeline. We continue to broaden our drug discovery engine to unlock new difficult-to-drug targets with compelling biology through deep computational expertise, a breadth of internal drug discovery expertise, and key partnerships. We look forward to multiple key milestones in the coming year."

Mr. Keiper will provide an overview of the company’s progress, pipeline, and anticipated milestones for 2025 and beyond at the 43rd Annual J.P. Morgan Healthcare Conference on Monday, January 13, 2025 at 7:30 a.m. PT.

On January 9, 2025 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered therapies targeting cytokine pathways designed to address areas of unmet need for patients with a variety of cancers, reported it has reached the 75% of overall survival (OS) events necessary for the planned interim analysis of ARTISTRY-7, its potentially registrational trial of nemvaleukin in combination with pembrolizumab in platinum resistant ovarian cancer (PROC), and that it has extended its cash runway projection into Q1 2026 beyond key upcoming catalysts (Press release, Mural Oncology, JAN 9, 2025, View Source [SID1234649543]).

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The company expanded its pipeline in Q4 2024, by nominating two development candidates, one for its interleukin-18 (IL-18) program and one for its IL-12 program. MURA-8518 is designed to be a half-life extended, binding protein-resistant IL-18 in order to overcome the native cytokine’s limitations as a therapeutic. Mural expects to submit an Investigational New Drug (IND) Application or Clinical Trial Application (CTA) for a phase 1 trial of MURA-8518 in Q4 2025. MURA-7012 is comprised of targeted split IL-12 sub-units that preferentially self-assemble at the tumor site and are designed to limit systemic exposure.

"In just over a year since becoming an independent company, we have transformed Mural from a biotech with a binary readout expected in 2025 into a robust organization with multiple expected data catalysts. Not only have we stayed on track with our milestones as planned, we have also extended our cash runway into the first quarter of 2026 through operational efficiency," said Caroline Loew, Ph.D., CEO of Mural Oncology. "With two readouts in our late-stage trials on the horizon, nemvaleukin has the potential to become a new treatment option for patients with high unmet need in platinum-resistant ovarian cancer and mucosal melanoma. 2025 will be a pivotal year for Mural, and we look forward to advancing our clinical programs to bring value to patients and shareholders alike."

Upcoming catalysts:

Late Q1/early Q2 2025: Interim data readout of ARTISTRY-7, Mural’s potentially registrational phase 3 trial in PROC. The trial is evaluating nemvaleukin in combination with pembrolizumab versus investigator’s choice single agent chemotherapy. Consistent with Mural’s prior timing projections, the trial has now reached the 75% of OS events necessary for the planned interim analysis. The data will remain blinded to the company until after the independent data monitoring committee (IDMC) has reviewed the interim analysis, which is expected to be in late Q1/early Q2 2025. Consistent with interim analyses, there is a higher statistical bar for success at the interim analysis compared to the final analysis. If the hazard ratio meets this pre-specified higher bar for success at the interim analysis (0.727, or a 27.3% reduction in the risk of death assuming exactly 215 OS events), the company plans to submit a Biologics License Application (BLA) for nemvaleukin in combination with pembrolizumab for the treatment of PROC in 2025. If the hazard ratio does not meet the statistical threshold for success at the interim analysis and the company deems the study to have a high probability of success for the final analysis, Mural expects to continue the trial to the protocol-specified final OS analysis, where the maximum hazard ratio for success is 0.788, or a 21.2% reduction in the risk of death, assuming exactly 286 OS events. The company expects to report these final OS results in the second quarter of 2026, subject to event accrual.
Q2 2025: Top-line data readout of Cohort 2 of ARTISTRY-6, Mural’s potentially registrational phase 2 trial of nemvaleukin monotherapy in patients with unresectable or metastatic mucosal melanoma previously treated with immune checkpoint blockade. Nemvaleukin has been granted Orphan Drug Designation by the FDA for the treatment of mucosal melanoma. The target response rate in the ARTISTRY-6 trial is 25%. Mural believes that in this rare and highly aggressive tumor, which has historically had poor outcomes even in the first line setting, demonstrating durable responses with a response rate of 20-25% would be meaningful for patients, and would support a discussion with the FDA regarding a BLA submission and potential accelerated approval.
1H 2025: Preliminary data readout of Cohort 3 of ARTISTRY-6, an evaluation of a less-frequent intravenous (LFIV) dose of nemvaleukin monotherapy in patients with cutaneous melanoma. Patient enrollment in this cohort is now complete. If the data are promising, following subsequent clinical evaluation, LFIV dosing could offer a more convenient dosing regimen for patients and providers alike.
2H 2025: Preliminary data readout of Cohort 4 of ARTISTRY-6, an evaluation of a LFIV dose of nemvaleukin in combination with pembrolizumab in patients with cutaneous melanoma.
Q4 2025: Mural expects to submit an IND or CTA for a phase 1 trial of MURA-8518, its IL-18 development candidate.

On January 9, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with cancer, reported pipeline updates, including its plans to advance IMPT-314, a potentially best-in-class therapy for aggressive large B-cell lymphoma, into pivotal trials (Press release, Lyell Immunopharma, JAN 9, 2025, View Source [SID1234649542]). IMPT-314 is an autologous dual-targeting CD19/CD20 chimeric antigen receptor (CAR) T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.

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"Based on the positive initial clinical data reported at ASH (Free ASH Whitepaper) and the promising emerging clinical profile, we are accelerating the development of IMPT-314 as a potentially transformative product with differentiated benefit in overall and complete response rates as well as duration of response over first-generation CD19 CAR therapies in patients with aggressive large B-cell lymphoma," said Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. "Having presented an initial dataset that demonstrated an overall response rate of 94% and a complete response rate of 71% in patients treated in the 3rd-line+ setting, we are focusing our resources on advancing IMPT-314 for patients with large B-cell lymphoma in both the 2nd and 3rd line+ settings. To ensure a sustainable cost structure that delivers multiple clinical readouts with our current balance sheet, we have streamlined and focused our pipeline and organization to prioritize investment in IMPT-314 and early-stage research programs for solid tumors."

Pipeline Focus

Lyell is focused on advancing next-generation CAR T cell therapies with the potential to deliver higher response rates and longer duration of responses for patients with hematologic malignancies and solid tumors. Lyell is developing products enhanced with its novel technologies and manufacturing protocols.

In hematologic malignancies, Lyell is focused on advancing products designed to deliver improved outcomes over first-generation CD19 CAR T cell therapies. Lyell’s lead program, IMPT-314, is a dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the currently approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma. IMPT-314 is designed with a true ‘OR’ logic gate to target B-cells that express either CD19, CD20 or both and is manufactured through a process that enriches for CD62L-expressing cells to generate more naïve central memory CAR T cells with enhanced stemlike features and antitumor activity.

To realize the potential of cell therapy for solid tumors, Lyell is also developing next-generation CAR T-cell product candidates enhanced with anti-exhaustion and additional arming technologies, and manufactured with proprietary protocols. These approaches are designed to endow CAR T cells with attributes needed to drive durable tumor cytotoxicity and achieve consistent and long-lasting clinical responses – the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile tumor microenvironment.

Upcoming Milestones and Financial Outlook

For IMPT-314, a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate for the treatment of large B-cell lymphoma:

Present data from the ongoing Phase 1-2 trial in mid-2025, including more mature data from the 3rd line+ cohort and initial data from the 2nd line cohort
Present more mature clinical data from the 2nd line cohort in late 2025
Initiate a pivotal trial in the 3rd line+ setting in mid-2025
Initiate a pivotal trial in the 2nd line setting by early 2026
For early-stage solid tumor programs:

Submit first IND application for a new solid tumor CAR T-cell product candidate in 2026
To accelerate the pivotal trials of IMPT-314 and focus resources on next-generation solid tumor CAR T-cell programs in preclinical development, Lyell has streamlined its operations and is discontinuing development of LYL119, its ROR1-targeting CAR T cell product candidate, and IMPT-514, an autoimmune disease program previously initiated by ImmPACT Bio that was acquired by Lyell in connection with its acquisition of ImmPACT Bio.

Lyell expects net cash use in 2025 to be $175 million – $185 million, which extends its cash runway further into 2027 through multiple clinical milestones.

J.P. Morgan Healthcare Conference

Members of Lyell’s senior management team will present and participate in the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15th at 9:00 am PT.

A live webcast of the presentation can be accessed through the Investors section of the Company’s website at www.lyell.com. Following the live presentation, a replay of the webcast will be available on the Company’s website.

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 responses as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.

IMPT-314 is designed with a true ‘OR’ logic gate to target, with high potency, 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 process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate more naïve central memory CAR T cells with enhanced stemlike features and 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.

Initial data from 23 patients with relapsed or refractory, CAR T-naive large B-cell lymphoma who received IMPT-314 were reported at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The efficacy evaluable population consisted of 17 patients. The overall response rate was 94% (16/17 patients), with 71% (12/17 patients) achieving a complete response 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.