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Plus Therapeutics Presents New Data Highlighting Clinical Benefit and Safety of REYOBIQ in the ReSPECT-LM Clinical Trial for Patients with Leptomeningeal Metastases

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).

Avistone Announces Preclinical Results for ANS03, a Novel Type II ROS1/NTRK Inhibitor in Overcoming Clinically Relevant ROS1/NTRK Resistance Mutations at AACR Annual Meeting 2025

On April 15, 2025 Avistone Biotechnology Co., Ltd ("Avistone"), an innovative biotechnology company focused on precision oncology therapeutics, reported that the preclinical data for ANS03, its novel, orally bioavailable Type II ROS1/NTRK tyrosine kinase inhibitor (TKI), will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Avistone Pharmaceuticals, APR 15, 2025, View Source [SID1234651953]).

The details of the poster presentation are provided below:

Poster title: ANS03, a novel, orally bioavailable small-molecule type II ROS1/NTRK inhibitor, effectively overcomes clinically relevant ROS1/NTRK resistance mutations and exhibits potent antitumor activity in preclinical tumor models
Abstract Number: 828
Session: Targeted Therapies and Combinations 1 (Clinical Research)
Location: Poster section 34, Board 16
Session Date/Time: April 27, 2025 | 2:00-5:00 PM CDT

The battle against ROS1 and NTRK fusion-positive cancers has seen major advances with next-generation tyrosine kinase inhibitors (TKIs) like repotrectinib, taletrectinib, which effectively suppress the recurrent resistance mutations such as G2032R (ROS1 SF mutation). However, the emergence of new resistance mechanisms, such as ROS1 L2086F (Cβ6) mutation, presents a growing clinical challenge and unmet need.

Non-clinical studies of ANS03 showed it was a potent, orally bioavailable Type II ROS1/NTRK inhibitor with remarkable activity against various pathogenetic ROS1/NTRK alterations (including ROS1: G2032R, D2033N, L2086F; NTRK: G667C, G595R-G667C) and with favorable absorption, distribution, pharmacokinetics, efficacy, and tolerability profiles.

"These findings suggest ANS03 could become the preferred therapeutic option for patients developing resistance to current ROS1/NTRK inhibitors," said Dr. Hepeng Shi, CEO of Avistone. "Its distinct Type II binding mode provides comprehensive coverage of clinically-relevant mutations while maintaining good CNS activity, which offers the potential to be explored as frontline therapy."

ANS03 is currently being evaluated in a global phase I study (NCT06716138) in adult patients with locally advanced or metastatic solid tumors harboring with ROS1 alterations, and in adult and pediatric patients (aged≥12 years) with NTRK alterations.

InnoCare Announces the Acceptance of New Drug Application for pan-TRK Inhibitor Zurletrectinib in China

On April 15, 2025 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on the treatment of cancer and autoimmune diseases, reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) accepted a New Drug Application (NDA) for its new generation pan-TRK inhibitor zurletrectinib (ICP-723) for the treatment of adult and adolescent patients (12 to 18 years old) with advanced solid tumors harboring NTRK gene fusions (Press release, InnoCare Pharma, APR 15, 2025, View Source [SID1234651952]).

In the registrational trial for adult and adolescent patients with NTRK fusion-positive solid tumors, zurletrectinib demonstrated outstanding efficacy with a good safety profile. Zurletrectinib was also shown to overcome acquired resistance to the first-generation TRK inhibitors.

Meanwhile, the Company is accelerating the registrational trial for pediatric patients (2 to 12 years old).

Dr. Jasmine Cui, the co-founder, chairwoman and CEO of InnoCare, said, "Zurletrectinib has demonstrated outstanding efficacy and safety profile in adult, adolescent, and pediatric patients with tumors harboring NTRK fusion genes, bringing better treatment options for patients with solid tumors. The Company is expanding the scope of its solid tumor pipelines through a combination of targeted therapies, immune-oncology approaches, and cutting-edge ADC technology, looking forward to meeting the unmet needs of patients with solid tumors early."

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%1. 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 highly unmet clinical needs in this area due to lack of effective treatment options.

Toragen, Inc. Provides Update on Phase 1 Clinical Trial of TGN-S11 as Monotherapy and in Combination with Keytruda® in Patients with Stage 4 HPV-Associated Cancers

On April 15, 2025 Toragen, Inc., a San Diego-based clinical-stage biotechnology company focused on developing uniquely selective drugs targeting cancers caused by viruses, reported positive safety data from its Phase 1 trial of TGN-S11, a small molecule inhibitor of the human papillomavirus (HPV) E5 oncogene protein, in patients with cancers associated with HPV (Press release, Toragen, APR 15, 2025, View Source [SID1234651951]).

This Phase 1 trial was an open-label, non-randomized study in multiple cohorts of patients with relapsed, resistant, or metastatic HPV-associated cancers. The study has been conducted in two parts: Part 1 was escalating doses of TGN-S11 as monotherapy and Part 2 was TGN-S11 in combination with Keytruda (pembrolizumab), a PD-1 checkpoint inhibitor. The dose escalation part consisted of four Cohorts of three to six patients on monotherapy with increasing doses of TGN-S11. The Keytruda combination part consisted of three Levels of three to six patients with increasing doses of TGN-S11 and the standard dose of Keytruda.

In Part 1, 18 patients were treated with TGN-S11 as monotherapy in 4 dose cohorts with no serious adverse events identified. In the 4th dose cohort, 2 patients developed non-serious dose-related toxicities; therefore, the maximum tolerated dose (MTD) was determined to be 300mg/day. One-third of the patients who received TGN-S11 monotherapy showed drug activity with decreases in tumor size and decreases in Tumor Tissue Modified Viral (TTMV) HPV DNA as measured by the NavDx test. In addition, 10 patients were treated in Part 2 in 3 dose levels evaluating TGN-S11 in combination with Keytruda with no safety issues. Half of these patients in this portion of the study showed drug activity with decreases in tumor size and/or decreases in TTMV-HPV DNA score. One of these patients had a 92% reduction in TTMV-HPV DNA score and 3 patients remain on treatment.

This Phase 1 trial met both primary endpoints of proving safety and reaching the maximum tolerated dose of TGN-S11. In addition, our data also shows that 53% of patients that reached at least 2 months of treatment showed drug activity.

Dr. Neil Clendeninn, CMO of Toragen, said, "TGN-S11 was well-tolerated as monotherapy and in combination with Keytruda and we are very excited to see evidence of activity based on the reduction in TTMV-HPV DNA score in this study in advanced cancer patients."

Based on these positive results, Toragen plans to proceed with the development of its second-generation inhibitor of the E5 oncogene protein, TGN-S15, which has demonstrated increased efficacy and decreased side effects in preclinical testing. TGN-S15 will advance to IND-enabling studies to support a first in human study in healthy volunteers and Phase 2 clinical trials targeting HPV-associated cancers.

Illumina and Tempus partner to drive the future of precision medicine through genomic AI innovation

On April 15, 2025 Illumina Inc. (NASDAQ: ILMN) and Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported a collaboration to accelerate clinical adoption of next-generation sequencing tests through novel evidence generation (Press release, Illumina, APR 15, 2025, View Source [SID1234651950]). The collaboration will combine leading Illumina AI technologies with Tempus’s comprehensive multimodal data platform to train genomic algorithms and ultimately accelerate clinical adoption of molecular testing for patients.

"In the era of true precision medicine, every patient who is battling complex disease should be routed to the optimal therapy based on molecular insights," said Everett Cunningham, chief commercial officer of Illumina. "We envision a world where the full range of molecular profiling is available as part of the standard of care—not just in cancer, but in cardiology, neurology, immunology, and every other category of disease."

Today, patients frequently miss the benefit of precision medicine because molecular profiling is not yet standard across disease areas and regions. This collaboration will leverage Tempus multimodal data to further improve Illumina’s AI-driven molecular analysis technologies and generate new insights supporting the clinical value of sequencing. These insights will be used to build evidence packages needed to standardize use of comprehensive genomic profiling and other molecular testing across all major diseases.

"By expanding our collaboration with Illumina, we are combining our strengths in technology and data analytics with their strengths in developing new sequencing technologies to drive forward innovation and advance precision medicine," said Terron Bruner, chief commercial officer of Tempus.

The program builds on a long-standing collaboration between the companies, which has focused on developing tools and assays to address gaps in testing needs from preemptive screening through therapy selection, health economics, and bioinformatics pipelines to improve patient outcomes and research.