On May 1, 2025 InnoCare Pharma (HKEX: 09969), a leading biopharmaceutical company for the treatment of cancer and autoimmune diseases, reported that its new generation pan-TRK inhibitor zurletrectinib (ICP-723) has been granted priority review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA), which accepted the New Drug Application (NDA) of zurletrectinib for the treatment of patients with advanced solid tumors harboring NTRK gene fusions recently (Press release, InnoCare Pharma, MAY 1, 2025, View Source [SID1234652465]). Priority review is one of the key policies introduced by the CDE to accelerate drug approval.

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In the registrational trial for patients with NTRK fusion-positive solid tumors, zurletrectinib demonstrated outstanding efficacy with a good safety profile.

Dr. Jasmine Cui, the co-founder, chairwoman and CEO of InnoCare, said, "We are delighted that zurletrectinib has been granted priority review. Zurletrectinib has demonstrated outstanding efficacy and a favorable safety profile. We anticipate it will provide better treatment options for eligible patients with solid tumors earlier."

Zurletrectinib is a pan-TRK inhibitor developed by InnoCare. British Journal of Cancer, part of leading science journal Nature, published a paper entitled "Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumors with on-target resistance to first-generation agents"1.

NTRK fusion genes occur in various types of adult and pediatric tumors. In some rare tumors, such as salivary gland carcinoma, secretory breast cancer, and infantile fibrosarcoma, the incidence of NTRK gene fusion exceeds 90%2. It is estimated that there are about 6,500 new cases of NTRK fusion-positive solid tumors are diagnosed in China each year. There are significant unmet clinical needs in this area due to lack of effective treatment options.

On May 1, 2025 Illumina, Inc. (NASDAQ: ILMN), and Ovation.io, Inc., an organization dedicated to building best-in-class multiomics datasets, reported the development of the largest commercially available clinical multiomic dataset from 25,000 patients treated with glucagon-like peptide-1 (GLP-1) receptor agonist therapies (Press release, Illumina, MAY 1, 2025, View Source [SID1234652464]). The dataset will be made available to the pharma community to advance drug discovery and development. This collaboration is the latest in a series of efforts to partner across the ecosystem, and deploy multimodal data to advance a deeper understanding of biology.

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One in eight adults in the United States have used a GLP-1 receptor agonist, according to a 2024 health tracking poll conducted by the Kaiser Family Foundation. However, roughly 40% of users with Type 2 diabetes do not respond effectively to GLP-1 receptor agonists, according to a study published in Diabetes & Metabolic Syndrome in 2024. The collaboration aims to accelerate GLP-1 therapy development, indication expansion research, and discovery of novel biomarkers and drug targets in nonresponsive populations.

"The power of whole-genome and multiomic insights to impact all diseases is coming into focus, and metabolic disease is a prime example," said Todd Christian, senior vice president of Services, Arrays, and Genomic Access at Illumina. "This collaboration and its novel clinical dataset will be crucial to advancing the next wave of these potential life-changing therapies, and ensuring more patients can benefit from them."

Through a multiyear agreement, Illumina and Ovation are launching an integrated dataset of phenotypic, genomic, and proteomic data from patients treated with GLP-1 therapies, including therapy-responsive and nonresponsive populations. This critical dataset is designed to enable deeper understanding of molecular pathways involved in GLP-1 response, which can unlock new indications where GLP-1 therapies may be effective, as well as new biomarkers and drug targets for patients who do not respond to GLP-1 therapies today.

"We’re proud to collaborate with Illumina to develop one of the world’s largest WGS omics datasets, supporting the millions of patients with diabetes and obesity," said Marty Miller, chief revenue officer of Ovation. "Through this effort—and for the first time at scale with the inclusion of proteomics—we aim to equip the pharmaceutical industry with the insights needed to better understand the varying effectiveness and side effects of GLP-1 receptor agonists across individual patients."

The initiative leverages end-to-end Illumina NGS technologies to sequence 25,000 whole genomes and to profile the protein expression of 5000 samples, using the Illumina Protein Prep (IPP) assay, which detects 9500 human proteins per sample. The initiative aims to include a longitudinal subset of proteomes from paired samples collected before and after patient exposure to GLP-1 therapy.

IPP enables the discovery of new protein quantitative trait loci (pQTL), which are emerging as a vital tool for drug discovery, linking genetic variation with protein expression data and disease or other phenotypes. The pQTL dataset is processed using Illumina’s industry-leading DRAGEN secondary analysis and the newly released Illumina Connected Multiomics for tertiary analysis and visualizations. The data is stored for future large-scale studies in Illumina Connected Analytics.

Ovation is providing samples from its biobank of over 1.7 million de-identified, consented, and tokenized samples, linked to rich, longitudinal phenotypic data.

Ovation announced an original agreement with Illumina in 2024, aimed at addressing challenges in drug development through genomic data solutions. The initial phase of the collaboration focused on creating pilot datasets from patients with liver disease, chronic kidney disease, and patients treated with GLP-1 receptor agonists. The companies plan to explore opportunities to scale the GLP-1 dataset and generate others in the future.

On May 1, 2025 Blue Earth Therapeutics reported further progress in development of its radiohybrid, lutetium-labelled, PSMA targeted, investigational radioligand therapy, with enrolment of the first two patients in a Phase 2 clinical trial (Press release, Blue Earth Therapeutics, MAY 1, 2025, View Source [SID1234652463]). The primary measure of efficacy in the study will be the proportion of patients achieving a ≥50% reduction in PSA levels, as well as assessing radiographic progression-free survival and patient safety (NCT05413850).

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The study is testing multiple dosing regimens that focus on delivering higher radiation doses when tumor burden is usually highest, at the beginning of treatment. This approach contrasts to pivotal studies of earlier radioligand therapies where the same dose was administered in every cycle2 regardless of tumor burden. The study design aligns with the US FDA Project Optimus initiative where the goal is that drug developers optimize dosing early in a product’s development to deliver the best possible benefit risk profile.

Loading doses will be delivered by either a) giving a higher dose in the first two treatment cycles, or b) shortening the time between administration of the first three doses to three weeks from the usual six weeks. The study is also designed to test the clinical benefit of administration of high total doses of administered radioactivity, up to 60GBq. The Phase 1 data confirmed a high ratio of uptake in tumor tissues vs. uptake in healthy tissues such as kidneys and salivary glands1.

David Gauden DPhil, CEO of Blue Earth Therapeutics said, "This is an important step forward in the development of Lutetium (177Lu) rhPSMA-10.1 injection and builds on the strong data seen in the Phase 1 clinical trial. Commencement of treatment of patients at full intended therapeutic dosing levels provides a great opportunity to assess the benefit this therapy can bring to patients. With up to 20 sites enrolling patients, we expect to see first results from the study early next year. We are grateful to the physicians and patients of Biogenix Molecular in Florida, who have just recruited the first patients for the study."

About metastatic prostate cancer
In 2025 it is estimated that there will be 50,055 new cases of metastatic prostate cancer in the United States (de novo diagnoses plus recurrence from earlier stage diagnoses).3 Five-year survival for newly diagnosed metastatic prostate cancer is low, 36.6%.4 While death rates from prostate cancer have declined over the past three decades4, there is still considerable room to improve patient outcomes.

About Radiohybrid Prostate–Specific Membrane Antigen (rhPSMA)
rhPSMA compounds are referred to as radiohybrid ("rh"), as each molecule possesses four distinct domains. The first consists of a Prostate–Specific Membrane Antigen–targeted receptor ligand. It is attached to two labelling moieties which may be radiolabelled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy, all of which are joined together by a modifiable linker which can be used to modulate important pharmacokinetic characteristics. Radiohybrid PSMA offers the potential for targeted treatment for men with prostate cancer and originated at the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics.

On May 1, 2025 Intima Bioscience, a clinical stage oncology company focused on curative intent in solid tumor cancers, reported data from a first-in-human study using CRISPR knockout of the intracellular immune checkpoint CISH in T cells administered to patients with metastatic colorectal cancer at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Intima Bioscience, MAY 1, 2025, View Source [SID1234652462]).

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"Over the last decade, the fast-growing field of Immuno-Oncology has nearly entirely focused on neutralizing cell surface targets. Inhibiting promising intracellular checkpoint targets like CISH have dramatic anti-cancer potential, but have traditionally been thought to be undruggable," said Emil Lou, M.D., Ph.D., Principal Investigator of the clinical trial and Professor of Hematology and Oncology at the University of Minnesota. "This first-in-human study used CRISPR/Cas9 deletion of CISH as a model system to evaluate the viability of CISH checkpoint inhibition as a novel strategy for solid tumor immunotherapy."

In a featured oral presentation at the AACR (Free AACR Whitepaper) Meeting, Dr. Lou provided the first report of the effects of administering neoantigen reactive TILs with knockout of CISH, a gene which encodes cytokine-inducible SH2-containing protein, in patients with metastatic colorectal cancer. The study’s results were contemporaneously published in The Lancet Oncology. This dataset consisted of 12 patients who had received multiple lines of therapy, including standard-of-care chemotherapy and biologic agents.

"This is the first clinical trial to test genetic disruption of CISH as a harbinger of a new class of immune checkpoints that have pan cancer activity and are not limited by any given tumor’s surface PD-L1 expression. Multiple genomic screens have converged on nominating these intracellular immune checkpoints as highly promising therapeutic targets to advance immunotherapy beyond the current limits of the PD1/PD-L1 paradigm," said Christopher A. Klebanoff, M.D., a senior advisor to the study and immunotherapy expert at Memorial Sloan Kettering Cancer Center (MSK), Associate Attending, Laboratory Head, and Member, Immuno-Oncology Program (IOP).

Key points from this proof-of-concept clinical trial:

The most common severe adverse events included expected hematological events attributable to the preparative lymphodepleting chemotherapy regimen or expected effects of IL-2 (12 patients [100%]). No episodes of high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome were observed. No serious adverse events or patient deaths resulted from targeting the CISH checkpoint.
A patient with young adult/early onset Stage IV colorectal cancer resistant to multiple lines of chemotherapy and immunotherapy was treated on this trial and developed a clinical complete response which is ongoing after more than two years.
Detailed molecular and genetic analysis of this patient demonstrated ongoing persistence of CISH inhibited T cells synchronous with the ongoing complete response to this treatment.
As a testament to the end stage nature of the treated patient population, the median progression-free survival on this trial was 57 days, and median overall survival was 129 days.
A companion scientific paper entitled "CISH, a novel intracellular immune checkpoint, in comparison and combination to existing and emerging cancer immune checkpoints" comprehensively evaluates the intrinsic single agent and combination anti-cancer activity of CISH relative to other prevailing immune checkpoints. This preprint has been submitted for peer review.

Dr. Lou added: "In metastatic colorectal cancer, where treatment options are limited and survival outcomes are uniformly fatal, CISH represents a promising new target that may overcome the limitations of current immunotherapies. We believe these data, including an exceptional complete response attributed to CISH knockout, resoundingly support the potential role of CISH checkpoint inhibition in addressing this significant unmet need and underline the possibility of small molecule drugging of CISH to democratize access to patients beyond this proof-of-concept cell therapy clinical trial."

NB: The National Cancer Institute of the NIH formally defines an exceptional response as a complete response in which less than 10% of patients respond overall.

About CISH
The cytokine-inducible SH2-containing protein CISH is an intracellular cancer immune checkpoint that functions as a negative modulator of T-cell receptor (TCR) signaling and cancer neoantigen recognition. CISH negatively regulates antigen-specific cytokine release and T cell expansion via its capacity to bind PLC-γ1, a proximal mediator of TCR complex signaling. Inhibition of CISH in T cells is believed to help overcome immune evasion regardless of tumor type or PD-L1 expression.

On May 1, 2025 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported that data from its Phase 2 clinical trial of lucicebtide (formerly known as ST101), a first-in-class antagonist of C/EBPβ, in patients with glioblastoma will be featured during an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 30-June 3, 2025, in Chicago and online (Press release, Sapience Therapeutics, MAY 1, 2025, View Source [SID1234652461]).

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Presentation Details:

Title: "Use of lucicebtide (ST101) in glioblastoma patients by antagonism of C/EBPβ-dependent mesenchymal cell transition and immunosuppressive M2 macrophage polarization"
Abstract Number: 2016
Session Type and Title: Rapid Oral Abstract – Central Nervous System Tumors
Session Date and Time: Saturday, May 31, 2025, 3:00 pm – 4:30 pm CDT
Presenting Author: Fabio M. Iwamoto, MD, Division of Neuro-Oncology, New York-Presbyterian/Columbia University Irving Medical Center

More information can be found on the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting website.

About Lucicebtide (formerly known as ST101)

Lucicebtide, a first-in-class antagonist of C/EBPβ, has completed the main portion of a Phase 2 dose expansion study in recurrent glioblastoma (rGBM) (NCT04478279). An ongoing window-of-opportunity sub-study is evaluating lucicebtide in combination with radiation and temozolomide in patients with newly diagnosed GBM (ndGBM) and as a monotherapy in patients with rGBM, with patients receiving ST101 before and after surgical resection in both cohorts. ST101 has been granted Fast Track designation for rGBM from the U.S. Food and Drug Administration (U.S. FDA) and orphan designations for glioma from the U.S. FDA and the European Commission.