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Ashvattha Therapeutics Reports the Ability to Tune Nanomedicines to Image Neuroinflammation in Multiple Sclerosis Patients and Tumor Associated Macrophages in Cancer at SNMMI Annual Meeting

On June 23, 2025 Ashvattha Therapeutics ("Ashvattha"), a clinical-stage company advancing a new class of nanomedicine therapeutics that traverse tissue barriers to selectively target and reprogram activated cells in regions of inflammation, reported promising results from two novel nanomedicine radiotracers at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, taking place June 21 – 24, 2025 in New Orleans (Press release, Ashvattha Therapeutics, JUN 23, 2025, View Source [SID1234654048]).

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The two agents are designed to address key gaps in neuroinflammation and cancer imaging by targeting activated microglia and macrophage, respectively.

Neuroinflammation Imaging Validation
Data presented in the poster titled "[18F]F-Flurimedrimer, a Novel Nanomedicine Radiotracer, Selectively Targeting Activated Microglia in Human Brain" showed that flurimedrimer (FMD), an investigational radiotracer engineered to selectively target activated microglia within the human brain, provided important validation of selective brain targeting. FMD is constructed from a hydroxyl dendrimer Generation 4 (HD4) with superior blood brain barrier penetration in regions of neuroinflammation compared to larger HDs (HD5 or HD6). The [18F]F-FMD was safe and well tolerated with rapid renal clearance, no tissue retention, and no brain uptake in healthy volunteers. [18F]F-FMD demonstrated selective uptake in areas of neuroinflammation in a primary progressive multiple sclerosis patient while showing no uptake in age-matched healthy volunteers, highlighting its specificity for activated microglia. These results support the agent’s potential for precise imaging of neuroinflammatory conditions.

Novel Cancer Imaging Approach
Data presented in the poster titled "A Novel Nanomedicine Radiotracer, Selectively Targeting Tumor Associated Macrophages" showed that hydroxyl dendrimers Generation 6 (HD6)-NOTA, a radiotracer with superior tumor-associated macrophage (TAM) uptake compared to other hydroxyl dendrimers of smaller size (HD4 or HD5), achieving 41.6% ID/g peak tumor uptake at 48 hours post-dose in tumor-bearing mice. TAMs are immune cells known to promote tumor growth and treatment resistance and can constitute a significant portion of tumor mass. The radiotracer successfully targeted macrophages throughout tumor structures, supporting its potential for diagnostic oncology imaging. A follow-on study using a therapeutic isotope with HD6 will be presented at a future conference.

"These results highlight the ability to tune our hydroxyl dendrimer platform to selectively target key cell populations in neurology and oncology," said Jeff Cleland, PhD, CEO of Ashvattha Therapeutics. "FMD’s (HD4) selective brain uptake in regions of neuroinflammation demonstrates the potential to image and treat neurological diseases with neuroinflammation. For cancer, our tuned nanomedicine, HD6-NOTA, has selective TAM uptake enabling cancer imaging, and the potential to selectively kill TAMs with a therapeutic isotope. Together, they underscore our platform’s unique ability to leverage our nanomedicine for precision targeting of activated cells – without relying on traditional targeting ligands."

Anixa Biosciences Initiates Dosing in Fourth Cohort in its Ovarian Cancer CAR-T Clinical Trial

On June 23, 2025 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported that it has dosed its first patient in the fourth dosage cohort in the ongoing Phase 1 clinical trial evaluating its novel chimeric antigen receptor-T cell (CAR-T) therapy for recurrent ovarian cancer (Press release, Anixa Biosciences, JUN 23, 2025, View Source [SID1234654047]). The study is being conducted through a research partnership with Moffitt Cancer Center ("Moffitt") under the direction of Dr. Robert Wenham, Chair of the Gynecologic Oncology Program at Moffitt, the principal investigator.

The fourth cohort in the trial will receive a dose of three million CAR-positive cells per kilogram of body weight, representing a thirtyfold increase from the first cohort. No dose-limiting toxicities were observed in the third cohort, enabling advancing to the fourth dosage cohort. This planned escalation marks a key step in assessing the safety and therapeutic effect of CAR-T cell therapy in patients with ovarian cancer.

Anixa’s FSHR-mediated CAR-T technology targets the follicle-stimulating hormone receptor (FSHR), which research indicates is exclusively expressed on ovarian cells, tumor vasculature, and certain cancer cells. The first-in-human trial (NCT05316129) is enrolling adult women with recurrent ovarian cancer who have progressed after at least two prior therapies. The study is designed to evaluate safety, identify the maximum tolerated dose, and monitor efficacy.

Dr. Amit Kumar, Chairman and CEO of Anixa, stated, "With no dose-limiting safety issues observed in the third cohort, we have advanced to a higher dose level that is thirty times greater than the starting dose. Although the study is primarily focused on safety at these early, low-dose levels, we have seen promising signs of potential efficacy. "

Harbour BioMed Enters Global Strategic Collaboration with Otsuka to Advance BCMAxCD3 Bispecific T-Cell Engagers

On June 22, 2025 Harbour BioMed (HKEX: 02142), a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology and oncology, reported a global strategic collaboration with Otsuka Pharmaceutical Co., Ltd. ("Otsuka") to advance BCMAxCD3 bispecific T-cell engagers for the treatment of autoimmune diseases (Press release, Harbour BioMed, JUN 22, 2025, View Source [SID1234654042]).

Under the terms of the agreement, Otsuka is granted an exclusive license to develop, manufacture, and commercialize HBM7020, a BCMAxCD3 bispecific T-cell engager globally, excluding Greater China (Mainland China, Hong Kong, Macau and Taiwan). In return, Harbour BioMed will receive a total of $47 million in upfront and near-term payments. The company is also eligible for additional payments of up to $623 million upon the achievement of specified development and commercial milestones, as well as tiered royalties on future net sales. This strategic collaboration establishes a foundation for potential future partnerships between the two companies in the T-cell engager area.

"We are delighted to collaborate with Otsuka, a global healthcare leader renowned for its innovative approach to addressing unmet medical needs," said Dr. Jingsong Wang, Founder, Chairman, and CEO of Harbour BioMed. "This collaboration underscores the strength of Harbour BioMed’s proprietary Harbour Mice and HBICE technology platforms, which enable the rapid development of fully human bispecific antibodies with optimized safety and efficacy profiles. By leveraging our unique capabilities, we are well-positioned to advance next-generation biotherapeutics that can make a meaningful difference in patients’ lives worldwide."

Makoto Inoue, President and Representative Director of Otsuka Pharmaceutical, noted, "Otsuka is expanding our development pipeline in the autoimmune disease field by leveraging the antibody drug platform of our subsidiary Visterra, and the small molecule drug discovery platform of our subsidiary Jnana. HBM7020 is expected to demonstrate efficacy in a broad range of autoimmune diseases in which B cells play a major role in disease pathogenesis, and we hope to contribute further to the field of specialized autoimmune diseases and thereby benefit patients."

About HBM7020

HBM7020 is a BCMAxCD3 bispecific antibody generated using Harbour BioMed’s fully human HBICE bispecific technology and Harbour Mice platform. It is designed to crosslink target cells and T cells by binding to BCMA and CD3 on the cell surface, leading to potent T cell activation and targeted cell elimination. By incorporating dual anti-BCMA binding sites for enhanced cell targeting and monovalent-optimized CD3 activity to minimize cytokine release syndrome (CRS), HBM7020 has demonstrated potent cytotoxicity with broad therapeutic potential in both immunological and oncological diseases. In August 2023, HBM7020 obtained IND clearance from the National Medical Products Administration (NMPA) to commence a Phase I trial for cancer in China.

Exelixis Announces Zanzalintinib in Combination with an Immune Checkpoint Inhibitor Improved Overall Survival in STELLAR-303 Phase 3 Pivotal Trial in Patients with Metastatic Colorectal Cancer

On June 22, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported positive topline results from the STELLAR-303 phase 3 pivotal trial in which zanzalintinib in combination with atezolizumab (Tecentriq) demonstrated a statistically significant improvement in overall survival (OS) versus regorafenib in the intent-to-treat (ITT) population of patients with previously treated non-microsatellite instability (MSI)-high metastatic colorectal cancer (CRC) (Press release, Exelixis, JUN 22, 2025, View Source [SID1234654040]). These topline findings are from the final analysis conducted by the Independent Data Monitoring Committee of one of the dual primary endpoints of the STELLAR-303 phase 3 trial. The trial will proceed to the planned final analysis for the other dual primary endpoint of OS in patients without liver metastases (non-liver metastases, NLM).

The safety profiles of zanzalintinib in combination with atezolizumab and of regorafenib were generally consistent with what has been previously observed, and no new safety signals were identified.

The ITT population consisted of all randomized patients, regardless of the presence of liver metastases. The NLM subgroup consisted of patients who did not have active liver metastases at baseline as determined by investigator assessment.

"The STELLAR-303 results, which showed a survival benefit with the combination of zanzalintinib and atezolizumab versus regorafenib across all randomized patients with previously treated metastatic colorectal cancer, marks an important first milestone for our zanzalintinib pivotal development program," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "We look forward to discussing the findings with regulatory authorities and presenting the detailed results at an upcoming medical conference."

Secondary endpoints of STELLAR-303 include progression-free survival, objective response rate and duration of response in the ITT population and in the NLM subgroup of patients. Exelixis plans to submit detailed results of STELLAR-303 for presentation at an upcoming medical conference.

About STELLAR-303
STELLAR-303 (NCT05425940) is a global, multicenter, randomized, phase 3, open-label study that randomized 901 patients 1:1 to either zanzalintinib (100 mg) in combination with atezolizumab or regorafenib. The study includes patients with previously treated non-MSI-high metastatic CRC. The dual primary endpoints of the study are OS in the ITT population and in the NLM subgroup of patients. Presence of liver metastases at baseline for all enrolled patients was determined by investigator assessment. Secondary endpoints include progression-free survival, objective response rate and duration of response in the ITT population and in the NLM subgroup of patients. More information about the trial is available at ClinicalTrials.gov.

About Zanzalintinib
Zanzalintinib is a third-generation oral tyrosine kinase inhibitor that inhibits the activity of receptor tyrosine kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including colorectal cancer, kidney cancer, head and neck cancer and neuroendocrine tumors.

Zanzalintinib is an investigational agent that is not approved for any use and is the subject of ongoing clinical trials.

About CRC
CRC is the third most common cancer and the second leading cause of cancer-related deaths in the U.S.1 Approximately 154,000 new cases will be diagnosed in the U.S. with around 53,000 expected deaths from the disease in 2025.1 CRC is most frequently diagnosed among people aged 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaska Native descent.2 Nearly a quarter of CRC cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 16.2%.2 The liver is the most common site for CRC metastasis. Liver metastases significantly impact survival, with a median five-year survival rate of less than 14% when treated with palliative chemotherapy.

Molecular Partners and Orano Med present preclinical data on mesothelin-targeting Radio-DARPin candidate MP0726 at SNMMI 2025

On June 22, 2025 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company") and Orano Med, a clinical-stage radiopharmaceutical company and a pioneer in the development of targeted alpha-particle therapies (TAT) with 212Pb (lead-212), reported the debut of MP0726, its Radio-DARPin candidate targeting mesothelin (MSLN) and will present preclinical data in an oral presentation at the 2025 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), taking place June 21-24 in New Orleans, LA, USA (Press release, Molecular Partners, JUN 22, 2025, View Source [SID1234654039]).

The oral presentation outlines encouraging early preclinical proof-of-concept data showing that MP0726 binds with high affinity and selectivity to the membrane-proximal domain of MSLN without being impacted by shed MSLN. In vivo results in a MSLN tumor model show a favorable biodistribution with substantial uptake of the Radio-DARPin in MSLN-positive tumors, while other organs showed limited accumulation. At 24 hours post injection, tumor accumulation was up to 34%, resulting in a tumor to kidney ratio of up to 4.5.

MP0726 leverages the unique properties of DARPins to selectively bind membrane-bound MSLN, a promising target for ovarian cancer due to its differentiated expression profiles – high in tumor, and lower in healthy tissues. High levels of shed MSLN can act as a decoy receptor and have historically hampered the development of MSLN-targeted therapeutics. MP0726 is being co-developed under Molecular Partners’ strategic partnership with Orano Med.

"Our collaboration with Molecular Partners has been delivering substantial progress in a short time, reflecting the skills, passion and strong complementarity of our teams. This progress highlights the effectiveness of our joint R&D efforts, enabling us to identify and advance differentiated clinical candidates that address important unmet medical needs. With its world-class R&D capabilities, the ownership of a virtually unlimited supply of the starting isotope, and fully-integrated manufacturing supply chain, Orano Med is uniquely positioned to support the development of these important potential new medicines", said Arnaud Lesegretain, CEO of Orano Med.

"We are proud to advance our second Radio-DARPin candidate into development, together with our partner Orano Med, for patients with MSLN expressing cancers. The promising preclinical data indicate a favorable biodistribution profile and highlight the unique approach to targeting MSLN with MP0726," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.

MP0726 represents the second Radio-DARPin program to move into pre-clinical development. The first Radio-DARPin program, MP0712 targeting DLL3, is on track to dosing the 1st patient in a Phase 1 study in the US in the second half of 2025.

Details of the presentation:

Preclinical characterization of a Lead-212 Radio-DARPin Therapeutic to selectively target membrane-bound mesothelin in solid tumors
Date & Time: 24 June 2025; 2:50-3:00 pm CST
Session: SS38 Radiopharmaceutical Oncology – Preclinical and Early Phase (2:30-3:45 pm CST)

About 212Pb-based Radio-DARPins
Molecular Partners’ Radio-DARPin platform is being developed to provide a unique and innovative delivery system for radioactive payloads, with exquisite targeting capabilities of DARPins combined with the optimally balanced safety and tumor killing of 212Pb. DARPins are ideal vectors for efficient delivery of therapeutic radionuclides to solid tumors, while overcoming some historic limitations of radioligand therapy approaches, thanks to their small size as well as high specificity and affinity. Molecular Partners and Orano Med are developing targeted alpha radio-therapeutics against up to ten targets, including the tumor-associated protein Delta-like ligand 3 (DLL3) and mesothelin (MSLN).