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.

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 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 Baylink Biosciences reported that new preclinical data from its portfolio will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 25-30, 2025, in Chicago, IL (Press release, Baylink Biosciences, APR 15, 2025, https://www.baylinkbio.com/post/lorem-ipsum-dolor-sit-amet-consectetur-adipiscing-elit [SID1234652037]). These data provide insights into the potential of Baylink’s innovative Antibody Drug Conjugate platform in treatment of cancers with high unmet medical need. Scientists at Baylink have invented a platform technology that enables the delivery of a variety of payloads including hydrophobic chemotherapy and protein degrader drugs at a high drug to antibody ratio while preserving stability and pharmacokinetic characteristics to enable application in ADC format. The innovative linker panel combined with Baylink’s proprietary payloads create a deep well of products, including dual payload ADC designs, and Degrader Antibody Conjugates (DAC) with potential application in cancer treatment.

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Preclinical data from Baylink’s most advanced candidate (BLB-101) will be presented. BLB-101 is an antibody drug conjugate designed to target Claudin 6/9 and deliver the topoisomerase 1 inhibitor, exatecan in a highly efficient manner with a drug to antibody ratio of 8. Claudin 6 (CLDN6) is a tight junction protein that is highly expressed in various human cancers, including ovarian cancer, endometrial cancer, and non-small cell lung cancer (NSCLC), but is absent in normal adult tissues. Claudin 9 (CLDN9), which shares high homology with CLDN6, exhibits a similar expression pattern—being nearly undetectable in normal tissues but upregulated in ovarian and endometrial cancers.

Data generated to support the rationale for Baylink’s innovative linker platform will also be presented. Baylink’s linker platform is designed to reduce non-specific uptake into healthy tissues and cells while enhancing potency by improving ADC’s homogeneity, stability, PK, and efficacy. The platform also has the ability to deliver ADCs with multiple payload classes.

"We are very pleased to share these results from Baylink’s innovative antibody drug conjugate platform. The data presented at this year’s AACR (Free AACR Whitepaper) meeting demonstrate the potential for Baylink’s technology to overcome critical challenges in the ADC field," said Alice Chen, PhD, Chief Scientific Officer and Founder of Baylink. "In addition to sharing details on our platform technology, we are presenting data for one of our lead products, BLB-101, a novel antibody targeting CLDN6/9, conjugated to our linker BL001 delivering exatecan. We believe BLB-101 offers the potential for best in class performance for CLDN6/9+ tumors such as ovarian, endometrial, and lung cancer."

A linker platform for antibody drug conjugates (ADCs): expanding the therapeutic window

Poster number：7463

Session Date and Time: April 30, 2025, 9:00 AM – 12:00 PM

Preclinical evaluation of BLB-101, a topoisomerase-inhibitor-based anti-CLDN6/9 antibody-drug conjugate featuring a proprietary hydrophilic linker

Poster number：1578

Session Date and Time: April 28, 2025, 9:00 AM – 12:00 PM

About Baylink Biosciences innovative linker technology

Baylink’s linker technology was designed to overcome key challenges in the antibody drug conjugate field such as tumor resistance, lack of payload diversity, and narrow therapeutic window. Using proprietary, innovative linker designs, Baylink scientists created a panel of linkers enabling delivery of challenging drug payloads. Drugs that are hydrophobic in nature are problematic for delivery using traditional ADC linker technology. Baylink scientists incorporated design features into the linker technology that allows conjugation of these hydrophobic payloads with high DAR. Additionally, the linker technology effectively reduces non-tumor-antigen-specific uptake into healthy tissues and cells reducing potential for adverse events. The overall resulting ADCs have potential for better efficacy and safety. The platform is also enabling delivery of multiple payloads, so called dual payload ADCs.