On April 15, 2025 Accent Therapeutics, a clinical-stage biopharmaceutical company focused on novel, targeted, small molecule cancer therapeutics, reported that the first patient has been dosed in a first-in-human Phase 1/2 clinical trial evaluating the safety and tolerability of ATX-295, a potential best-in-class oral KIF18A inhibitor (Press release, Accent Therapeutics, APR 15, 2025, View Source [SID1234651949]). In addition, the company has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for ATX-295 for the treatment of adult patients with advanced/metastatic platinum-resistant or refractory ovarian cancer, and for ATX-559, a first-in-class potent and selective inhibitor of DHX9, for the treatment of adult patients with unresectable/metastatic dMMR/MSI-H colorectal cancer post checkpoint inhibitor treatment.

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"Cancers with high chromosomal instability, such as in certain ovarian, breast, and lung cancers, collectively affect a large patient population but have limited treatment options. With ATX-295 entering the clinic, we are excited to translate multiple years of KIF18A research into the development of a potentially best-in-class program," said Jason Sager, M.D., Chief Medical Officer of Accent Therapeutics. "With the launch of our Phase 1/2 clinical trial of ATX-295, we now have two investigational drugs in the clinic, bringing us closer to achieving our mission of transforming cancer care. Additionally, receiving FDA Fast Track designation for both of our lead assets underscores the power of our approach and the potential for these investigational drugs to urgently address high unmet medical needs."

ATX-295 is a selective inhibitor of KIF18A, a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability, but not in healthy cells. Accent has demonstrated that its novel, potent, and selective small molecule KIF18A inhibitor displays selective dose-dependent tumor growth inhibition in preclinical models, including in high grade serous ovarian cancer and triple negative breast cancer, supporting its advancement to the clinic.

The ATX-295 Phase 1/2 open-label, dose-escalation and expansion study (NCT06799065) is designed to evaluate the molecule’s safety profile at multiple dose levels, assessing the tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of orally administered ATX-295. The trial is enrolling patients with locally advanced or metastatic solid tumors, including high-grade serious ovarian cancer.

The initiation of the Phase 1/2 ATX-295 study follows closely after Accent’s initial clinical asset, ATX-559, a first-in-class oral inhibitor of DHX9, entered clinical evaluation in late 2024. Both clinical assets have been granted Fast Track status by the FDA. Fast Track designation is designed to facilitate the development and expedite the review of novel drug candidates that address serious conditions marked by unmet medical need, with the aim of accelerating patient access to novel treatment options.

Accent will present new preclinical data supporting the continued clinical assessment of ATX-295 and ATX-559 at the 2025 AACR (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago, Illinois. Accent will also present a trial-in-progress update on the ATX-559 Phase 1/2 clinical trial at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting taking place May 30 – June 3 in Chicago, Illinois.

About ATX-559
ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, shown to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need. DHX9 has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability, making it a compelling novel oncology target. In addition to exploiting key tumor vulnerabilities in DNA repair deficient backgrounds (e.g., BRCA) and hyper-mutated states (e.g., MSI-H/dMMR), Accent is exploring the sensitivity of other tumor types to DHX9 inhibition, and the potential to combine DHX9 inhibitors with other cancer treatments to maximize its full potential for helping patients. Accent retains full worldwide rights to ATX-559, currently being evaluated in a Phase 1/2 clinical trial (NCT06625515), and the DHX9 program.

About ATX-295
Accent’s second lead program, ATX-295, is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability, but not in healthy cells. KIF18A inhibitor treatment results in rapid cell death for cancers with an abnormal number of chromosomes (aneuploid) in vitro and in vivo, while cells with normal numbers of chromosomes (euploid) are unaffected. Accent retains full worldwide rights to the KIF18A program, currently being evaluated in a Phase 1/2 clinical trial enrolling solid tumor patients (NCT06799065).

On April 15, 2025 Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported it will host a virtual key opinion leader (KOL) event featuring Zev A. Wainberg, MD, Professor of Medicine at University of California, Los Angeles (UCLA) and co-director of the UCLA GI Oncology Program, on Wednesday, April 23, 2025 at 2:30 p.m. ET (Press release, Leap Therapeutics, APR 15, 2025, View Source [SID1234651948]).

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Dr. Wainberg will connect with Leap’s Chief Medical Officer, Cynthia Sirard, MD, to discuss the unmet need and how sirexatamab (DKN-01) may improve upon the current treatment landscape for previously treated patients with advanced microsatellite stable (MSS) colorectal cancer (CRC).

The event will focus on reviewing the positive data from Part B of the Phase 2 DeFianCe study of sirexatamab in second-line patients with advanced MSS CRC. Sirexatamab, Leap’s most advanced clinical program, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein.

A live Q&A will follow the discussion. A replay of the event will be available for a limited time on the Investors page of the Company’s website at View Source

About Zev A. Wainberg, MD
Zev A. Wainberg, MD, is the Professor of Medicine at UCLA and co-director of the UCLA GI Oncology Program. He was trained in medical oncology and hematology at UCLA. He completed his residency training at Albert Einstein College of Medicine and received his MD from the Sackler School of Medicine, New York Program at Tel Aviv University. His research involves a variety of clinical trials in multiple gastrointestinal cancers including pancreas, colon, gastric, and esophageal. Dr. Wainberg’s laboratory-based research efforts involve the testing of novel therapeutics against all gastrointestinal cancers. Currently, he is the recipient of several grants focused on the targeting of cancer stem cells and in molecular classification of gastrointestinal cancers.

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.

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 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.