On January 9, 2025 TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics ("BBOT" or the "Company"), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BBO-8520, an investigational oral therapy for the treatment of adult patients with previously treated, KRASG12C-mutated metastatic non-small cell lung cancer (NSCLC) (Press release, BridgeBio, JAN 9, 2025, View Source [SID1234649558]).

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BBO-8520 is designed to inhibit the "ON and OFF" state to provide optimal target coverage and to address KRASG12C amplification and receptor tyrosine kinase activation – the two key mechanisms of adaptive resistance to current "OFF" state inhibitors. It drives substantial tumor growth inhibition in multiple preclinical models, even after emergence of resistance to sotorasib, an FDA approved "OFF" state inhibitor of KRASG12C.i The discovery of BBO-8520 was the result of a collaboration between the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research, Lawrence Livermore National Laboratory, and BBOT.

"Receiving Fast Track designation for BBO-8520 is a significant milestone in our efforts to overcome the limitations of existing therapies for KRASG12C-mutant cancers," said Yong Ben, MD, Chief Medical and Development Officer of BBOT. "BBO-8520 represents a first-in-class approach with potential to address high unmet medical needs and shift the paradigm for cancer treatment. We will continue to work closely with the FDA to expedite the development of BBO-8520, which is currently being evaluated in a Phase 1 study (NCT06343402) of KRASG12C NSCLC patients pre-treated with first generation KRASG12C "OFF" inhibitors or with no prior KRASG12C targeted therapy experience."

Fast Track designation is intended to help rapidly advance the development and review process for promising therapeutic candidates for serious conditions that may fill an unmet medical need.

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.

On January 9, 2025 TriSalus Life Sciences, Inc. ("TriSalus" or the "Company") (Nasdaq: TLSI), TriSalus Life Sciences seeks to transform outcomes for patients with solid tumors by integrating our innovative delivery technology with standard-of-care therapies and our investigational immunotherapy, reported the publication of research titled, "Pressure Enabled Drug Delivery (PEDD) Significantly Increases Intraarterial Delivery of Embolic Microspheres to Liver Tumors in a Porcine Model," in the peer-reviewed Journal of Vascular and Interventional Radiology (Press release, TriSalus Life Sciences, JAN 9, 2025, View Source [SID1234649559]). The study, conducted in a transgenic tumor model, highlights the superior performance of the TriNav Infusion System in delivering Embospheres into liver tumors when compared to delivery with a traditional microcatheter.

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Key Findings:

Improved Tumor Penetration: PEDD achieved a 227 % increase (p=0.029) in the concentration of fluorescently labeled Embospheres within tumor tissue compared to a traditional microcatheter.
Improved Tumor Selectivity: The tumor-to-normal (T:N) ratio rose from 2.7 for a traditional microcatheter to 4.2 when delivered by PEDD, indicating more precise tumor targeting and reduced off-target delivery.
Increased Peritumoral Delivery: Delivery to peritumoral regions increased by 209% (p=0.045), demonstrating PEDD’s ability to overcome challenging tumor associated microenvironments.
"This study further validates the potential of TriNav using the PEDD approach to transform the treatment of liver tumors," said Bryan F. Cox, Ph.D., Chief of Research for TriSalus. "By significantly enhancing therapeutic delivery and sparing healthy tissue, PEDD offers a promising advancement for patients whose outcomes may be limited by conventional delivery methods."

The study was conducted using a transgenic porcine (Oncopig) liver tumor model, employing fluorescent imaging and advanced deep-learning algorithms to quantify therapeutic delivery with millimeter-scale resolution. Results showed the TriNav Infusion System using the PEDD approach markedly outperforms traditional microcatheters in delivering embolic microspheres into liver tumors.

These findings add to the growing body of clinical and real-world evidence supporting PEDD’s ability to improve the delivery of therapeutic agents for patients with primary and metastatic liver cancers.

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 Biocytogen (HKEX: 02315), a global biotech company dedicated to discovering and developing novel antibody therapeutics, reported the licensing of its fully human antibodies to SOTIO Biotech, a clinical-stage biopharmaceutical company owned by PPF Group (Press release, Biocytogen, JAN 9, 2025, View Source [SID1234649560]). The licensing agreement will advance the development of an innovative antibody-drug conjugate (ADC) targeting a novel tumor antigen, under the option and license agreement established between the companies. Biocytogen’s fully human antibody will support the development of SOT109, SOTIO’s new ADC candidate aimed at the treatment of colorectal cancer and other gastrointestinal (GI) cancers.

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Biocytogen’s innovative RenMice platform offers an extensive library of fully human antibodies targeting over 1,000 antigens, with over 400,000 off-the-shelf antibody sequences. The RenMab platform is specifically engineered to generate high-quality monoclonal antibodies characterized by strong immune responses, high affinity, and high specificity, without the need for additional in vitro humanization, leading to substantial time and cost savings in downstream development, expediting the development and translation of cutting-edge bispecific, multispecific antibodies, and ADC therapies.

"We are thrilled to see the remarkable progress achieved through our collaboration with SOTIO," said Yuelei Shen, Ph.D., president and chief executive officer of Biocytogen. "The fully human monoclonal antibodies developed using our RenMab platform exhibit exceptional binding and internalization capabilities, along with excellent developability. By utilizing Synaffix’s platform and combining it with SOTIO’s extensive experience in ADC development, SOT109 has been developed as a highly promising candidate, offering new hope for the treatment of colorectal and other GI cancers."

"SOT109 holds tremendous promise as a transformative treatment for colorectal cancer and other GI cancers, marking the next milestone from our innovative ADC platform. Our collaboration with Biocytogen has been instrumental in identifying a fully human and selective mAb candidate that demonstrates excellent cross-species reactivity, binding affinity, and internalization properties," said Martin Steegmaier, Ph.D., chief scientific officer of SOTIO. "We are now in the final stages of clinical candidate selection for the program, and plan to commence IND-enabling studies this month."

Under the terms of the agreement, SOTIO will pay Biocytogen an option exercise fee at license execution. Biocytogen will also be eligible to receive success-dependent development and regulatory milestone payments, commercial milestone payments, and low single-digit royalties on net sales.