On April 15, 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 that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to LYL314 (formerly IMPT-314) for the treatment of adult patients with relapsed and/or refractory large B-cell lymphoma after two or more prior lines of therapy (Press release, Lyell Immunopharma, APR 15, 2025, View Source [SID1234651936]). LYL314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response as compared to the approved CD19‑targeted CAR T-cell therapies for the treatment of aggressive large B-cell lymphoma (LBCL).

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RMAT designation provides all the benefits of the Fast Track and Breakthrough Therapy designation programs, including early interactions with the FDA. LYL314’s RMAT designation was granted based on promising early data from the ongoing Phase 1/2 clinical trial.

"The RMAT designation for LYL314, is based on promising clinical data from our ongoing Phase 1/2 trial and highlights the transformative potential of this next-generation CAR T-cell therapy to address the unmet needs of patients with aggressive large B-cell lymphoma," said Lynn Seely, M.D., president and chief executive officer of Lyell. "We believe that by targeting both CD19 and CD20 with equal potency and manufacturing with a process that enriches for more naïve and central memory CAR T cells, LYL314 has the potential to offer patients with aggressive B-cell lymphoma more complete responses and longer duration of response than first-generation CAR T-cell therapies that only target CD19. LYL314 has now received both Fast Track Designation and RMAT designation in the 3rd or later line setting and we look forward to working closely with the FDA as we continue to accelerate this promising CAR T-cell therapy into two pivotal programs for patients."

Initial data from the Phase 1/2 trial of LYL314 were presented at the American Society for Hematology 2024 Annual Meeting in December 2024, including data from 23 patients with relapsed or refractory LBCL in the 3rd or later line setting who received LYL314. The efficacy evaluable population consisted of 17 patients. The overall response rate was 94% (16/17) of patients, with 71% (12/17) of 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 experiencing a response at last follow-up. In the safety evaluable population of 23 patients, no Grade 3 or greater cytokine release syndrome (CRS) was reported. Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 13% (3/23) of patients with a median time to ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy.

Additional clinical updates from the Phase 1/2 trial of LYL314 are planned for 2025. The company expects to present more mature data from the ongoing Phase 1/2 trial from patients being treated in the 3rd or later line setting and initial data from patients in the 2nd line setting in mid-2025 and to present more mature data from patients treated in the 2nd line setting in late 2025. Two pivotal programs for LBCL are planned, including one for patients treated in the 3rd or later line setting expected to be initiated in mid-2025 and another for patients treated in the 2nd line setting expected to be initiated by early 2026.

The RMAT designation is a program under the 21st Century Cures Act that is intended to expedite the development and review of regenerative medicine therapies for serious or life-threatening diseases or conditions. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the regenerative medicine therapy has the potential to address unmet medical needs for such disease or condition.

RMAT designation provides all Breakthrough Therapy designation features, including early interactions to discuss any potential surrogate or intermediate endpoints. RMATs may be eligible for accelerated approval based on previously agreed-upon surrogate or intermediate endpoints that are reasonably likely to predict long-term clinical benefit.

About LYL314

LYL314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response as compared to the approved CD19‑targeted CAR therapies for the treatment of LBCL. LYL314 is designed as a true CD19/CD20 "OR" logic-gated CAR targeting either CD19 or CD20 with full potency, and the cell therapy product is manufactured with a process that enriches for CD62L+ cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity.

In addition to RMAT, LYL314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed and/or refractory LBCL in the 3rd or later line setting.

On April 15, 2025 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company, reported that following review of data from its phase 2 ARTISTRY-6 trial in melanoma and previously announced results from the phase 3 ARTISTRY-7 trial in platinum-resistant ovarian cancer, the company is discontinuing all clinical development of nemvaleukin alfa and plans to immediately commence the exploration of strategic alternatives focused on maximizing shareholder value (Press release, Mural Oncology, APR 15, 2025, View Source [SID1234651944]). Mural has engaged Lucid Capital Markets, LLC to act as its financial advisor in connection with the exploration of strategic alternatives. The company had approximately $144.4 million of cash, cash equivalents, and marketable securities as of December 31, 2024. In conjunction with today’s announcement, Mural plans to reduce its workforce by approximately 90%.

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ARTISTRY-6, cohort 2 is a phase 2, single-arm trial evaluating nemvaleukin as a monotherapy in 92 patients with mucosal melanoma with a minimum follow-up of at least six months. A review of the topline data from this cohort showed that the primary endpoint was not achieved. Mural also conducted a review of preliminary data from ARTISTRY-6, cohort 3, evaluating less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma, and did not observe a level of activity that warranted continuation. Based on the totality of these data, together with the interim overall survival results from ARTISTRY-7 as announced on March 25, 2025, Mural will discontinue all clinical development of nemvaleukin.

Mural plans to explore potential strategic alternatives including, but not limited to, an offer for or other acquisition of the company, merger, business combination, or other transaction. While the company has not set a timetable for completion of this process, further updates and developments will be disclosed as appropriate or where necessary under regulatory requirements. There can be no assurance that the exploration of strategic alternatives will result in the company pursuing a transaction or that any acquisition or other transaction involving the company will be completed, nor as to the terms on which any acquisition or other transaction will occur, if at all.

The company confirms that, as at the date of this announcement, it is not in receipt of any approaches and not in active discussions with any potential offeror.

Irish Takeover Rules Considerations

Mural is subject to the Irish Takeover Panel Act, 1997, Irish Takeover Rules 2022 (the "Irish Takeover Rules"), which have certain implications on some of the strategic alternatives to be explored by the company. As the exploration of strategic alternatives is expected to include consideration of potential offers for the company, following the publication of this announcement Mural is now considered to be in an "offer period" as defined in the Irish Takeover Rules and the dealing disclosure requirements of Rule 8 of the Irish Takeover Rules as summarized below will apply.

The Irish Takeover Panel has granted a dispensation from the requirements of Rules 2.4(b) and 2.4(c) of the Irish Takeover Rules such that any potential offeror will not be required to be publicly identified as a result of this announcement for so long as the strategic evaluation is ongoing. Such parties should nonetheless be mindful of their obligations under the Irish Takeover Rules, including in particular with respect to confidentiality under Rule 2.1 and the circumstances in which an announcement may be required under Rule 2.2. If a potential offeror has any doubts about its obligations pursuant to the Irish Takeover Rules, it should contact its financial adviser(s) and, where applicable, it should also consult with the Irish Takeover Panel.

This is an announcement under Rule 2.4 of the Irish Takeover Rules and is not an announcement of a firm intention by any party to make an offer under Rule 2.7 of the Irish Takeover Rules.

On April 15, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported the online availability of new data on its lead compound REYOBIQ (rhenium Re186 obisbemeda) in an abstract for both an oral presentation and a poster to be presented at the Nuclear Medicine and Neurooncology conference to be held May 9-10, 2025 in Vienna, Austria (Press release, Plus Therapeutics, APR 15, 2025, View Source [SID1234651962]).

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The abstract, titled, "Rhenium Obisbemeda (REYOBIQ) in Leptomeningeal Metastases," highlights additional data from the Company’s completed Phase 1 ReSPECT-LM dose escalation trial demonstrating a dose dependent increase in the average absorbed dose to the cranial and spinal subarachnoid space reaching 253Gy in Cohort 5. Neuroimaging response data was available for 16 patients as of the data cutoff with five of those (31%) showing a partial response. An additional seven patients showed stable disease by neuroimaging through day 112 for a Clinical Benefit Rate (complete response + partial response + stable disease) of 75%. Additionally, a clinical response based on the physician evaluation showed a decrease in disease findings in two of 14 evaluable patients (14%) and 10 patients showed stable findings through day 112 for an 86% Clinical Benefit Rate. Furthermore, there was no dose limiting toxicity (DLT) observed in the first four cohorts, with a grade 4 DLT (thrombocytopenia), one in each of Cohorts 5 and 6.

Finally, RNA sequencing of LM cells showed early induction of apoptosis, with an innate immune response followed by an increase in T cells and an adaptive immune response by Day 28. Further details can be found here; the Company will provide additional data and explanation following the meeting.

"This newly-presented ReSPECT-LM data further reinforces our confidence in the potential utility of REYOBIQ in these critically ill patients with the devastating diagnosis of Leptomeningeal Metastases," said Marc H. Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "Reyobiq can be delivered at very high doses of radiation to the cancer at the recommended phase 2 dose and shows promising response data across multiple parameters while simultaneously being well tolerated by normal organs and tissues."

About Leptomeningeal Metastases (LM)
LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells, yet there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

About REYOBIQ (rhenium Re186 obisbemeda)
REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy specifically formulated to deliver direct targeted high dose radiation in CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. REYOBIQ has the potential to reduce off target risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue, and gamma energy for real-time imaging. REYOBIQ is being evaluated for the treatment of recurrent glioblastoma and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).

On April 15, 2025 Telix Pharmaceuticals Limited (ASX: TLX, NASDAQ: TLX, Telix, the Company) reported preliminary results from the Phase 2 IPAX-Linz study of TLX101 (131I-iodofalan[1]) in recurrent high-grade glioma (brain cancer), substantiating the patient benefit seen in the IPAX-1 study (Press release, Telix Pharmaceuticals, APR 15, 2025, View Source [SID1234651946]).

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IPAX-Linz is a single-arm Phase 2 investigator-initiated trial (IIT). IPAX-Linz evaluates the safety, tolerability and preliminary efficacy of TLX101 therapy, in combination with external beam radiation therapy (EBRT). The target patient population is patients at first or second recurrence with high-grade gliomas (HGG), including glioblastoma.

Treatment with TLX101 was well tolerated with no serious adverse events reported. IPAX-Linz demonstrated encouraging preliminary efficacy data, indicating a median overall survival (OS) of 12.4 months from the initiation of treatment with TLX101, or 32.2 months from initial diagnosis[3]. This is consistent with the positive efficacy signal generated in the IPAX-1 study in patients at first recurrence, with only one prior resection and treatment with standard chemoradiotherapy. IPAX-1 reported a median OS of 13 months from the initiation of treatment with TLX101, or 23 months from initial diagnosis[4]. In comparison, recurrent glioblastoma patients treated with EBRT alone have a reported median survival of 9.9 months from treatment[5].

Eight patients were included in the study with adaptive dosing of intravenous TLX101 up to administered activity of 4 GBq before, and up to 2 GBq after, second line EBRT, administered in sequential injections. Inclusion criteria comprised patients with glioblastoma with current evidence of first or second recurrence after standard radiochemotherapy, at least six months since end of first line EBRT, and molecular imaging with Telix’s investigational PET[6] agent for glioma, TLX101-CDx (Pixclara[7], 18F-floretyrosine, or 18F-FET), indicating pathologically increased amino acid uptake. Surgery for relapsed tumors was allowed. Of the eight IPAX-Linz patients, five had MGMT unmethylated tumors[8], typically associated with especially poor prognosis.

Professor Josef Pichler, Kepler University Hospital, Austria, Principal Investigator in the IPAX-Linz, IPAX-1, and IPAX-2 studies, commented, "These preliminary results in relapsed patients showed that TLX101 treatment was very well tolerated, with no serious adverse events, at a higher dose than in previous studies. Early efficacy from IPAX-1 was corroborated, despite the poor prognostic parameters with MGMT unmethylated tumors and multiple relapses before commencing experimental therapy in this IPAX-Linz study. TLX101 continues to show significant potential to improve outcomes for patients living with high-grade glioma. These results also potentially support higher therapeutic doses in subsequent prospective controlled studies."

Dr. David Cade, Chief Medical Officer at Telix, said, "These are encouraging results, offering new options for patients with historically poor outcomes. We are grateful to Dr. Pichler and his team for building on the IPAX-1 study in a more advanced and complex study cohort that is also representative of a real-world patient population."

Preliminary results from IPAX-Linz will be presented by Dr. Pichler at the Nuclear Medicine and Neurooncology (NMN) Symposium taking place in Vienna, Austria from 9 – 10 May 2025. Visit the event website for further information: View Source

TLX101 Development Program and Registration-Enabling Study Update

Telix continues to investigate TLX101 in front-line and recurrent settings. IPAX-2, a Phase 1/2 study in front-line glioblastoma in combination with standard of care and using TLX101-CDx as a companion diagnostic, continues to recruit patients.

Telix has submitted for ethics approval a registration-enabling study of TLX101 in recurrent glioblastoma. Subject to approval this will enable patient enrolment to commence at Australian sites in H2 2025, ahead of international expansion. Following the successful pre-IND[9] meeting with the U.S. Food and Drug Administration (FDA) in Q4 2024, the Company is also on track to submit an IND application in H1 2025, with the goal of commencing the study at U.S. sites in H2 2025.

About TLX101

TLX101 (131I-iodofalan or 131I-IPA) is a systemically administered targeted radiation therapy that targets L-type amino acid transporter 1 (LAT1), which is typically over-expressed in glioblastoma. TLX101 therapy utilizes a small molecule approach due to the need to cross the blood brain barrier, the normal protective barrier that prevents many potential drug candidates entering the brain. TLX101 has received orphan drug designation in the U.S. and Europe for the treatment of glioma. TLX101 and TLX101-CDx have not received a marketing authorization in any jurisdiction.

On April 15, 2025 Pilatus Biosciences, pioneering biologics targeting metabolic checkpoints, reported that it will present new research on its lead candidate, PLT012, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting (Press release, Pilatus Biosciences, APR 15, 2025, View Source [SID1234651947]). The presentations will include an oral symposium by co-founder and Chair of the Scientific Advisory Board (SAB), Prof. Ping-Chih Ho, and a poster session by Lead Scientist, Dr. Yi-Ru Yu. These efforts highlight PLT012’s potential as a novel therapeutic approach for immune-cold solid tumors. PLT012 is currently in late-stage preclinical development and progressing toward its first-in-human clinical trial.

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Event Participation and Presentations

Pilatus Biosciences will participate at the AACR (Free AACR Whitepaper) 2025 Annual Meeting, held April 27-30, 2025, with the following presentations:

Oral presentation: Prof. Ping-Chih Ho, co-founder and Chair of the SAB, will present during the Major Symposium SY21 – Immunometabolism and Metabolic Fitness in Tumors. The talk, titled "Reprogramming the Tumor Microenvironment with a Single Punch – Our Journey from Bench to Bedside", is scheduled for April 28, 2025, at 1:15 PM.
Poster presentation: Dr. Yi-Ru Yu, Lead Scientist, will present Abstract #6077 in Section 37, on April 29, 2025, from 2:00 PM to 5:00 PM. The poster will detail PLT012’s efficacy in addressing unmet needs in immune-cold solid tumors.
CEO Statement

"We are pleased to present our latest research at AACR (Free AACR Whitepaper) 2025," said Dr. Raven Lin, CEO of Pilatus Biosciences. "PLT012 reflects a differentiated approach—one that reawakens the immune system by targeting metabolic pathways, with the goal of extending the power of immunotherapy to patients who currently don’t benefit from it."

"PLT012 has earned FDA Orphan Drug Designation for liver and intrahepatic bile duct cancers. Its ability to reprogram the tumor microenvironment has led us to explore synergistic combinations, including bispecific antibodies (BsAb) and antibody-drug conjugates (ADCs), in preclinical studies across various solid tumor models, addressing critical unmet needs in oncology."

About PLT012

PLT012, is a humanized anti-CD36 antibody with a dual mechanism of action (MOA). It simultaneously inhibits immunosuppressive cell populations and enhances effector T cell function. Preclinical studies as a monotherapy have demonstrated its efficacy in both immune-hot and immune-cold tumor models, with a significant increase in GzmB-expressing CD8+ T cells and reductions in intratumoral Tregs and pro-tumorigenic macrophages. Additionally, PLT012 reshapes the exhaustion profile of cytotoxic CD8+ T cells by expanding both progenitor exhausted (Texprog) and terminally-exhausted (Texterm) populations with rejuvenated effector functions, leading to enhanced tumoricidal immunity. These findings suggest that PLT012, functioning as a metabolic regulator, may provide therapeutic benefits in cancer treatment, either as a monotherapy or in combination with immune checkpoint inhibitors such as PD-1 or PD-L1 inhibitors. Other than oncology, the unique MOA as a metabolic regulator also shows the potential of reprogramming the metabolic environment with associated benefits, e.g. liver functional improvement, thus laying the groundwork for targeting a broader spectrum of metabolic and immunological diseases.