BPGbio to Present New Data on Novel Glioblastoma Therapies at SNO 2024

On November 21, 2024 BPGbio, Inc., a leading biology-first, AI-powered clinical-stage biopharma company focused on mitochondrial biology and protein homeostasis, reported that it will co-present two pivotal studies with Stanford Medicine’s Department of Neurology at the Society for Neuro-Oncology (SNO) 2024 Annual Meeting, taking place November 21-24, 2024, in Houston, Texas (Press release, BPGbio, NOV 21, 2024, View Source [SID1234648568]). The presentations will highlight BPM31510 and BRG399—potential glioblastoma multiforme (GBM) therapies that were identified by the company’s proprietary NAi Interrogative Biology Platform, a causal AI-powered system designed to reveal hidden cause-and-effect relationships within patient biology.

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The first study, titled "Optimizing brain cancer therapy: balancing tumor eradication and normal tissue preservation with BPM31510," explores BPM31510’s superior ability to preserve healthy cells compared to standard cancer treatments in mouse, rat, and human glioblastoma cell lines. The study demonstrates BPM31510’s ability to effectively target and diminish cancer cells while selectively allowing the growth of healthy brain cells, an effect that standard treatments fail to achieve. Researchers also showed that the BPM31510 significantly improved survival in glioma implanted mice and rats compared to the control group, mirroring the results from the ongoing phase 2b trial on BPM31510 for GBM and highlighting BPM31510’s potential in brain cancer therapy.

The second study, titled "Improved anti-glioblastoma efficacy by BRG399, a novel oral microtubule binding agent," presents findings on BRG399’s anti-cancer activity. BRG399, a novel pan-cancer therapy, works by disrupting the cell division process in both solid and liquid tumors. BRG399 was also found to induce an immune memory response, protecting against tumor recurrence. The study confirmed that BRG399 can cross into the brain, target tumor cells, and improve survival in rat glioma models.

"Standard cancer treatments that focus solely on destroying tumors often harm healthy tissue in the process," said Seema Nagpal, M.D., principal investigator of the BPM31510 GBM phase 2b trial and Clinical Professor of Neurology and Neurological Sciences at Stanford Medicine. "These new treatments are taking novel targeted approaches on glioma cancer cells and we are excited to share the encouraging results from our studies with our peers and industry researchers."

"Our ongoing clinical and preclinical trials for BPM31510 and BRG399 are continuously deepening our understanding of these promising therapies," said Niven R. Narain, Ph.D., President and CEO of BPGbio. "By putting biology first, our NAi Platform has enabled us to optimize every aspect of these therapies, from dosing and timing to patient selection and potential indication expansion opportunities."

Poster Presentation Details:

Optimizing brain cancer therapy: balancing tumor eradication and normal tissue preservation with BPM31510
Date and Time: November 22, 2024, 7:30 p.m. – 9:30 p.m. CST
Location: Hall B3, George R. Brown Convention Center, Houston, Texas
Presenter: Abbas Khojasteh, Ph.D.
Abstract Number: DDDR-13

Improved anti-glioblastoma efficacy by BRG399, a novel oral microtubule binding agent
Date and Time: November 22, 2024, 7:30 p.m. – 9:30 p.m. CST
Location: Hall B3, George R. Brown Convention Center, Houston, Texas
Presenter: Stephane Gesta, Ph.D.
Abstract Number: DDDR-14
About BPM31510

BPM31510IV is BPGbio’s lead candidate in late-stage development for aggressive solid tumors such as glioblastoma multiforme (GBM) and pancreatic cancer. Other topical and oral formulations of the investigational agent are also being developed as a potential treatment for several rare diseases. The compound has demonstrated a tolerable safety profile and shown potential clinical benefits across multiple disease indications. Validated by BPGbio’s NAi Interrogative Biology platform, BPM31510 induces a hallmark shift in the tumor microenvironment (TME) by modulating mitochondrial oxidative phosphorylation in aggressive tumors, leading to cancer cell death. In many mitochondrial diseases, restoring CoQ10 levels can overcome the effect of mutations in genes that lead to mitochondrial dysfunction. BPM31510 has been granted Orphan Drug Designation by the FDA for GBM, pancreatic cancer, and epidermolysis bullosa (EB), as well as Rare Pediatric Disease Designation for primary CoQ10 deficiency and EB.

About BRG399

BRG399 is a BPGbio-developed candidate being studied for its therapeutic potential as a treatment for solid and liquid tumor cancers as well as diseases associated with inflammation. This experimental drug, a first-in-class, anti-mitotic agent with broad-spectrum anti-cancer activity and favorable pharmacological properties for clinical testing, is being designed for oral delivery. BRG399 is leading the new oncology drug pipeline for BPGbio which includes drug candidates uniquely targeting E2 enzymes.

Xenetic Biosciences, Inc. Presents Positive Preclinical Data Highlighting the Potential of Co-Administration of DNase I with CAR T Cells in a Murine Model of Melanoma Lung Metastasis

On November 21, 2024 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immune-oncology technologies addressing hard to treat cancers, reported the presentation of preclinical data investigating the potential of co-administration of deoxyribonuclease I (DNase I) with chimeric antigen receptor (CAR) T cells in a syngeneic B16 melanoma murine model of lung metastasis (Press release, Xenetic Biosciences, NOV 21, 2024, View Source [SID1234648553]).

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The poster titled, "The synergistic action of DNase I and CAR T cells enhances the therapeutic efficacy of adoptive immunotherapy in the syngeneic murine metastasis model," was presented on behalf of the Company by Alexey Stepanov, PhD, Institute Investigator at The Scripps Research Institute, at the AACR (Free AACR Whitepaper) Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer, held November 17-20, 2024, in Boston.

"Xenetic’s proprietary DNase-based oncology platform continues to demonstrate encouraging potential across a number of cancer indications and therapy modalities where there remains significant unmet need. CAR T cell therapy is a promising approach for treating various malignancies however, it has so far shown benefit only in hematological cancers, so efficacy in solid tumors remains an important goal. There, its antitumor activity is often hindered by a hostile, immunosuppressive tumor microenvironment (TME), which, in turn, is very often characterized by the presence of tumor-associated cell-free DNA (cfDNA) in the form of neutrophil extracellular traps (NETs). This research underscores the critical role of the NETs in modulating CAR T cell efficacy and the potential of DNase I to improve therapeutic responses for patients as an adjunctive treatment. Highlighted by the results seen with the co-administration of DNase I with murine EGFR-CAR T cells, we believe this approach has the potential to prolong survival compared to treatment with CAR T cell monotherapy," commented Reid Bissonnette, Ph.D., Executive Consultant for Translational Research and Development at Xenetic. "We continue to be encouraged by the data demonstrated to date and look forward to further exploring the translational potential of this combinatorial approach in enhancing cancer treatment."

For the preclinical study co-administration of DNase I with CAR T cells was investigated in a syngeneic B16 murine melanoma model of lung metastasis. Bioluminescent imaging of melanoma metastatic processes has shown that a single injection of DNase I (10 mg/kg) together with CAR T cells suppressed B16-EGFR lung metastasis at early stages in comparison to the vehicle control group and extended survival.

Key Highlights

Co-administration of single injection of DNase I (10 mg/kg) with murine EGFR-CAR T cells demonstrated to significantly suppress metastatic tumor burden, decreases the number of metastatic foci, and substantially prolongs survival compared to the CAR T cell monotherapy group.

Degrading of NETs by DNase I increases the amount of tumor-infiltrating T and CAR T cells and reduces the immunosuppressive effects of the TME.

Tumor immune cell infiltrate analysis revealed that the CD8 population of tumor-infiltrating CAR T cells from the DNase I treated group have lower expression of PD-1 and TIM-3 exhaustion markers.

Xenetic continues to advance its DNase-based oncology program towards Phase 1 clinical development for the treatment of pancreatic carcinoma and other locally advanced or metastatic solid tumors. Preliminary preclinical studies evaluating the combinations of DNase I with chemotherapy and DNase I with immuno-therapies in colorectal cancer models as well as CAR-T therapy have been completed.

U.S. FDA IND Clearance and First Patient Dosed in Australia for First Oncology ADC Program ALK201

On November 21, 2024 Allink Biotherapeutics, a clinical-stage biotechnology company pioneering next-generation bispecific antibody and ADC therapeutics, reported two significant milestones in the development of its lead program ALK201 (Press release, Shanghai Allink Biotherapeutics, NOV 21, 2024, View Source [SID1234648782]). The U.S. Food and Drug Administration (FDA) just cleared the company’s Investigational New Drug (IND) application, and first patient has been successfully dosed in Australia.

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Aberrations in FGF/FGFR2 signaling pathways are extensively documented in multiple malignancies, including gastroesophageal adenocarcinoma and breast cancer, correlating with poor clinical outcomes. ALK201 is an innovative ADC candidate targeting FGFR2b a critical oncogenic driver that has demonstrated clinical validation in various solid tumors . Leveraging the company’s proprietary hydrophilic linker and rationally selected payload, extensive preclinical studies of ALK201 have demonstrated robust anti-tumor activity and a promising therapeutic window, supporting its development as a potentially transformative ADC for FGFR2b-associated malignancies.

"The FDA’s IND clearance and first patient dosing in Australia represent significant milestones of ALK201, our first ADC program, advances into clinical development," said Hui Feng, Ph.D., Chief Executive Officer of AllinkBio. "The rapid advancement from first preclinical candidate to clinical stage exemplifies our R&D team’s operational efficiency. Encouraged by robust preclinical data demonstrating the anti-tumor efficacy in FGFR2b-expressing solid tumors. We are strategically advancing our clinical development to swiftly bring this potential therapeutic option to address unmet medical needs worldwide."

The Phase 1 multicenter clinical trial was designed to investigate ALK201, evaluating its safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity in patients with advanced solid tumors. The study consists of two sequential segments: a dose-escalation phase to determine the maximum tolerated dose (MTD), followed by a clinical expansion phase in which biomarker-guided patient populations will be further investigated.

AllinkBio team’s strategic vision and outstanding R&D execution capability have enabled the company growing from a preclinical to clinical stage biotech in about one year. The company’s deep expertise in molecule discovery and drug design, combined with a sophisticated biomarker-driven approach, has empowered swift development of a number of promising therapeutic candidates. AllinkBio is highly committed to bringing innovative precision therapeutics to patients in need.

About ALK201
ALK201 is a novel FGFR2b targeted ADC, in development as a potential treatment for multiple solid tumors. FGFR2b is a promising target with its mutations and overexpression comprehensively implicated in oncogenesis across diverse solid tumor landscapes. ALK201 is currently being evaluated in a Phase 1 study.

Precision BioSciences to Participate in Upcoming November Investor Conferences

On November 21, 2024 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for sophisticated gene edits, reported that it will participate in the following upcoming investor conferences (Press release, Precision Biosciences, NOV 21, 2024, View Source [SID1234648554]).

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JonesTrading Virtual Genetic Medicine Day
Date: Monday, November 25, 2024
Time: 11:00 AM ET
Panel Title: Next Generation of Gene Editing; Going Beyond "Cas"
Webcast Link: Register Here

AussieMit
Date: Friday, November 29, 2024
Time: 2:50 PM AEDT
Presentation Title: Emerging Therapies

A live webcast for the JonesTrading Virtual Genetic Medicine Day will also be accessible on Precision’s website in the Investors section under Events & Presentations at investor.precisionbiosciences.com. An archived replay of the webcasts will be available for approximately 30 days following the event.

Plus Therapeutics to Present Multi-Institutional Experience Using the CNSide™ Cerebrospinal Fluid Assay in Patients with Leptomeningeal Metastases

On November 21, 2024 CNSide Diagnostics, LLC, a wholly owned subsidiary of Plus Therapeutics, Inc. (Nasdaq: PSTV) ("Plus" or the "Company"), reported it will present data demonstrating the utility of the CNSide CSF Assay Platform in identifying mutations of key biomarkers in the CSF and their implications in treatment selection for LM (Press release, Plus Therapeutics, NOV 21, 2024, View Source [SID1234648555]). The data will be presented at the 2024 Society for NeuroOncology (SNO) Annual Meeting November 21-24 in Houston, Texas.

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"The data from CNSide suggests that biomarker mutation profiles in LM are dynamic, offering valuable insights for treatment strategies," said Marc H. Hedrick, M.D., Plus Therapeutics’ President and Chief Executive Officer. "The genetic drift observed in LM suggests an important role for radiotherapeutics such as Rhenium (186Re) Obisbemeda in addressing this challenging disease."

Key highlights:

CNSide CSF Assay evaluated 258 CSF samples across 66 patients with LM to analyze clinically relevant biomarkers
Fourteen biomarkers were assessed, including 11 by fluorescent in situ hybridization (FISH) and 3 by immunocytochemistry (ICC); 12 of the 14 biomarkers demonstrated at least one change during treatment
CNSide CSF FISH analysis detected biomarker changes in 88% (58/66) of patients, with newly identified actionable biomarkers in 26 cases
CNSide CSF ICC analysis revealed biomarker changes in 20% (13/66) of patients, with newly identified actionable biomarkers in 7 cases
The data will be presented on Friday, November 22, at 7:30 p.m. CST in a session titled, "The Oncogenic Flip in Patients with Leptomeningeal Metastatic Disease (LMD): Longitudinal Detection in Cerebrospinal Fluid Tumor Cells (CSF-TCs) Reveals Implications for Differential Treatment of the LMD Tumor," by Arushi Tripathy, M.D., from University of Michigan Department of Neurosurgery.

About CNSide Diagnostic, LLC
CNSide Diagnostics, LLC is a wholly owned subsidiary of Plus Therapeutics, Inc. that develops and commercializes proprietary clinical diagnostic laboratory assays, such as CNSide, designed to identify tumor cells that have metastasized to the central nervous system in patients with carcinomas and melanomas. The CNSide Assay Platform enables quantitative analysis and molecular characterization of tumor cells and circulating tumor DNA in the cerebrospinal fluid that inform and improve the clinical management of patients with leptomeningeal metastases. The Company is planning to commercialize CNSide in the U.S. in 2025.

About CNSide Test
The CNSide Cerebrospinal Fluid (CSF) Assay Platform consists of four laboratory developed tests (LDTs) used for diagnosis, treatment selection, and treatment monitoring of patients with Leptomeningeal Metastases (LM) from carcinomas or melanoma. The CNSide platform facilitates tumor cell detection / enumeration and biomarker identification using cellular assays (immunocytochemistry (ICC) and fluorescence in situ hybridization (FISH)) and molecular assays (next generation sequencing (NGS)). The CNSide CSF tumor cell enumeration LDT is currently being used in the ReSPECT-LM trial as an exploratory endpoint and is currently anticipated to become commercially available in 2025.

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 Rhenium (186Re) obisbemeda

Rhenium (186Re) 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. Rhenium (186Re) obisbemeda 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. Rhenium (186Re) obisbemeda 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).