berubicin (RTA 744) / CNS Pharma, WPD Pharma - LARVOL DELTA

Primary results of the randomized clinical trial of Berubicin vs Lomustine in patients with glioblastoma after failure of primary therapy: Data analysis and future possibilities (SNO 2025) - "Anthracyclines are characteristically used in combination for systemic therapy (e.g. leukemia, lymphoma, certain breast cancers), so there is promise that combination therapy will be the next pertinent approach to treatment of GBM. Evaluation of activity against a range of pediatric brain tumors is being pursued and preliminary results will be presented at the time of the conference."

Clinical • Brain Cancer • Breast Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Lymphoma • Solid Tumor • MGMT

Activity of Berubicin, a novel anthracycline, in Pediatric Diffuse Midline Glioma (DMG) cells: Preliminary data and future possibilities (SNO 2025) - "The preliminary results in patient-derived (PDX) DMG cell models show high activity (IC50 of 100-1000 nM), suggesting that there may be better efficacy than Lomustine (IC50 2-15 µM) and Temozolomide (>100 µM) against these same tumors. The study will be expanded to 8-10 different DMG models as well as in vivo testing incorporating combination therapy with ONC201 (dordaviprone), which is in clinical trials for DMG and under FDA review for approval expected later this year. Additional data from these studies will be presented and discussed."

Clinical • Brain Cancer • Cardiovascular • Diffuse Midline Glioma • Glioblastoma • Glioma • Pediatrics • Solid Tumor

Primary results of the randomized clinical trial of Berubicin vs Lomustine in patients with glioblastoma after failure of primary therapy: Data analysis and future possibilities (WFNOS 2025) - "Anthracyclines are characteristically used in combination for systemic therapy (e.g. leukemia, lymphoma, certain breast cancers), so there is promise that combination therapy will be the next pertinent approach to treatment of GBM. Evaluation of activity against a range of pediatric brain tumors is being pursued and preliminary results will be presented at the time of the conference."

Clinical • Brain Cancer • Breast Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Solid Tumor • MGMT

CNS Pharmaceuticals Announces Acceptance of Three Abstracts for Poster Presentation at the Society of NueroOncology (SNO) 30th Annual Meeting (ACCESS Newswire)

Clinical data • Glioblastoma

Activity of Berubicin, a novel anthracycline, in Pediatric Diffuse Midline Glioma (DMG) cells: Preliminary data and future possibilities (WFNOS 2025) - "The preliminary results in patient-derived (PDX) DMG cell models show high activity (IC50 of 100-1000 nM), suggesting that there may be better efficacy than Lomustine (IC50 2-15 µM) and Temozolomide (>100 µM) against these same tumors. The study will be expanded to 8-10 different DMG models as well as in vivo testing incorporating combination therapy with ONC201 (dordaviprone), which is in clinical trials for DMG and under FDA review for approval expected later this year. Additional data from these studies will be presented and discussed."

Clinical • Brain Cancer • Cardiovascular • Diffuse Midline Glioma • Glioblastoma • Pediatrics • Solid Tumor

Shared and non-overlapping functions of RECQL4 and BLM helicases in chemotherapeutics-induced glioma cell responses. (PubMed, BMC Cancer) - "Our results highlight the distinct roles of RecQ helicases in a response to chemotherapeutics and support a rationale for targeting RECQL4 as a therapeutic strategy in glioblastoma."

Journal • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • RECQL4

Thermodynamics and Kinetics of the Deintercalation of a Novel Anthracycline from Double-Stranded Oligonucleotide DNA. (PubMed, J Phys Chem B) - "We present an in silico study of the deintercalation of berubicin from two double-stranded oligonucleotide DNA sequences using well-tempered metadynamics (WT-MetaD), an enhanced sampling method widely employed for biomolecular systems...The rate-limiting step of the deintercalation mechanism is the transition from the intercalated to the reshuffling state, and the applied method allows a detailed description of it. Each state is described in terms of various properties, whose values are consistent with published computational and experimental studies on the interactions of other anthracyclines with DNA."

Journal

A Study of Berubicin in Adult Subjects With Recurrent Glioblastoma Multiforme (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: CNS Pharmaceuticals, Inc. | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Feb 2026

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

CNS Pharmaceuticals Announces Primary Analysis of Berubicin in Second Line Treatment of Glioblastoma Multiforme (CNS Pharma Press Release) - P2 | N=210 | NCT04762069 | Sponsor: CNS Pharmaceuticals, Inc. | "CNS Pharmaceuticals, Inc...announced the primary analysis of its clinical trial (NCT04762069) evaluating Berubicin, the first anthracycline demonstrated to extensively cross the blood-brain barrier (BBB), for the treatment of recurrent or progressive Glioblastoma Multiforme (GBM), an aggressive and usually fatal brain cancer. This analysis did not demonstrate statistically significant superiority in overall survival, the primary endpoint....Additionally, patients experienced no cardiotoxicity, a risk that curtails the use of other anthracyclines, and the safety profile continues to be favorable in this patient population."

P2 data • Glioblastoma

CNS Pharmaceuticals to Present at 6th Glioblastoma Drug Development Summit (CNS Pharma Press Release) - "CNS Pharmaceuticals, Inc...announced it will present at the 6th Glioblastoma Drug Development Summit being held February 18-20, 2025 in Boston, MA...As part of the event, Sandra Silberman, MD, PhD, Chief Medical Officer of CNS will give an oral presentation...As part of her presentation, Dr. Silberman will discuss how anthracyclines and taxanes have been indispensable in the treatment of cancer. Despite advancements, anthracyclines and taxanes have not been demonstrated to cross the Blood-Brain Barrier (BBB) in the absence of manipulation, however Dr. Silberman will provide an overview of the Company's reformulated anthracycline and a taxane currently in development, both of which appear to have significant penetration of the BBB and activity in GBM...The Company's lead program, Berubicin, is an anthracycline with demonstratable efficacy in Phase 1....CNS Pharmaceuticals expects to report primary analysis data from this study in the first half of 2025."

Clinical • P1 data • Glioblastoma

Characteristics of adverse reactions of three anti-glioma drugs in WHO-VigiAccess. (PubMed, Front Pharmacol) - "Antitumor medications such as Avastin, Berubicin, and Temozolomide have fundamentally transformed the treatment landscape for gliomas by exhibiting potent pharmacological effects on both high-grade and low-grade gliomas. There is limited correlation between antineoplastic medications and ADRs. Current comparative observational studies indicate that these inhibitors are associated with both common and specific adverse effects documented in the ADR reports submitted to the World Health Organization (WHO)."

Journal • Brain Cancer • CNS Tumor • Gastrointestinal Disorder • Glioma • Hematological Disorders • Leukopenia • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Pain • Rheumatology • Solid Tumor • Thrombocytopenia

CNS Pharmaceuticals Reports Third Quarter 2024 Financial Results (CNS Pharma Press Release) - "Clinical Development Progress: (i) Berubicin:...CNS Pharmaceuticals expects to report primary analysis data from its potentially pivotal study of Berubicin in the first half of 2025...; (ii) TPI 287:...CNS Pharmaceuticals plans to engage the FDA and obtain feedback on the design of a study focused on the registration of TPI 287 in recurrent GBM."

FDA event • P2 data • Glioblastoma

CNS Pharmaceuticals Announces Abstract Accepted for Poster Presentation at the 29th Annual Meeting of the Society for Neuro Oncology SNO 2024 (CNS Pharma Press Release) - "CNS Pharmaceuticals, Inc...announced that its abstract has been selected for poster presentation at the 29th Annual Meeting of the Society for Neuro-Oncology being held November 21-24, 2024 in Houston, TX."

P2 data • Glioblastoma

Unlocking the potential of hypoxia reduction in reshaping the glioblastoma tumor microenvironment for enhanced therapeutic synergy (SNO 2024) - "Evofosfamide treatment boosts tumor infiltrating Ki67+ proliferative CD8+ T cells (p<0.001) and heightens cytotoxicity, indicated by increased Granzyme B expression (p<0.01)...Hypoxia reduction also increases chemotherapy sensitivity, synergistically improving survival when combined with the blood-brain barrier-penetrating, immunogenic chemotherapy Berubicin (CT2A; vehicle MS=26d, Evo MS=36d, Berubicin MS=55d, Combo MS=70.5d). Future research will investigate the mechanisms underlying this shift towards a pro-inflammatory state, focusing on metabolic changes in CD8+ T cells and the impact of altered HIF pathway signaling on GAM polarization following hypoxia ablation. Understanding the therapeutic potential of reversing hypoxia-mediated immunosuppression could lead to novel combination therapies capable of overcoming resistance to both chemotherapy and immunotherapy in GBM."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • CNS Tumor • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor • CD8 • CD80 • GZMB • HAVCR2 • LAG3

Updates on a potentially pivotal trial CNS-201: A randomized, controlled trial of Berubicin vs. Lomustine after first-line therapy for Glioblastoma Multiforme (GBM) (SNO 2024) - "Berubicin, derived from doxorubicin (Dox), appears to cross the BBB and has shown significant central nervous system (CNS) uptake and anti-tumor activity. After the results of this interim analysis, CNS Pharmaceuticals completed enrollment with 252 patients evaluable for efficacy based on OS evaluations. Based on the decision of the DSMB, as well as the data presented herein, which includes comparative safety and balanced randomization of the arms, we will provide our recommendations and highlight our further development of Berubicin as a therapeutic option for patients with recurrent GBM as well as other CNS malignancies."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

CNS Pharmaceuticals Reports Second Quarter 2024 Financial Results (CNS Pharma Press Release) - "Berubicin:...CNS Pharmaceuticals expects to report topline results from its potentially pivotal study of Berubicin in the first half of 2025...CNS Pharmaceuticals plans to engage the U.S. FDA and obtain feedback on the design of a study focused on the registration of TPI 287 in recurrent GBM, with the goal of initiating the study in 2025."

FDA event • New trial • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

CNS Pharmaceuticals Announces Acceptance of Abstract for Poster Presentation at the 2024 SNO/ASCO CNS Cancer Conference (Yahoo Finance) - "CNS Pharmaceuticals, Inc...today announced that its abstract has been selected for poster presentation at the 2024 SNO/ASCO CNS Cancer Conference being held August 8-10, 2024 in Denver, CO."

Preclinical • Glioblastoma

A Study of Berubicin in Adult Subjects With Recurrent Glioblastoma Multiforme (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: CNS Pharmaceuticals, Inc. | Trial primary completion date: Sep 2024 ➔ Dec 2024

Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Interactions of a Novel Anthracycline with Oligonucleotide DNA and Cyclodextrins in an Aqueous Environment. (PubMed, J Phys Chem B) - "Selected structural and geometrical properties of all the complexes, which are all stable, are analyzed. Both cyclodextrins under consideration are widely utilized for drug delivery purposes, and a comparative investigation between their bound states with berubicin is carried out."

Journal

A Multicenter, Study of the Safety and Pharmacokinetics of Intravenously Infused Berubicin in Pediatric Patients With Progressive, Refractory, or Recurrent High Grade Gliomas (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: WPD Pharmaceuticals Sp. z o.o. | N=35 ➔ 0 | Trial completion date: Dec 2025 ➔ Dec 2023 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Dec 2025 ➔ Dec 2023

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Brain Cancer • CNS Tumor • Glioma • Oncology • Pediatrics • Solid Tumor

Berubicin in Adult Patients With Recurrent Glioblastoma Multiforme (WHO Grade IV) (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: WPD Pharmaceuticals Sp. z o.o. | N=50 ➔ 5 | Trial completion date: Oct 2025 ➔ Dec 2023 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2025 ➔ Dec 2023; Business decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

CNS Pharmaceuticals Reports Full Year 2023 Financial Results and Highlights Recent Corporate and Clinical Achievements (ACCESSWIRE) - "The Company expects to report topline data from its study of Berubicin in the first half of 2025, although it is impossible to accurately predict how long patients on the study may survive, which could impact the timing of the release of topline data."

P2 data • Glioblastoma

CNS Pharmaceuticals Achieves Completion of Planned Enrollment in Potentially Pivotal Study of Berubicin for the Treatment of Glioblastoma Multiforme (GBM) (CNS Pharma Press Release) - "CNS Pharmaceuticals, Inc...announced completion of planned enrollment in its global potentially pivotal study evaluating Berubicin, the Company's novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier, for the treatment of GBM, an aggressive and incurable form of brain cancer."

Enrollment closed • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

CNS Pharmaceuticals Announces Successful Interim Analysis of Efficacy and Safety Data in Potentially Pivotal Study of Berubicin (CNS Pharma) - "Enrollment expected to be complete in early Q1 2024...CNS Pharmaceuticals, Inc...announced the recommendation of the independent Data Safety Monitoring Board (DSMB) that the Company's ongoing global, potentially pivotal trial of the investigational agent, Berubicin for the treatment of glioblastoma multiforme (GBM) continue without any modification. The recommendation follows the DSMB's pre-specified futility analysis of unblinded (to the DSMB only) efficacy and safety data in the Company's trial of Berubicin versus Lomustine, a standard of care in patients with recurrent GBM. More specifically, the DSMB reviewed the primary endpoint of overall survival (OS) and secondary efficacy measures progression-free survival (PFF) and overall response rate (ORR), as well as safety data in evaluable patients. In order to support continuing the trial, Berubicin's efficacy had to be at least comparable to Lomustine's on the primary endpoint (OS)."

DSMB • Enrollment status • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

CNS Pharmaceuticals (NASDAQ: CNSP) Presents Updated Safety Data from Ongoing Potentially Pivotal Study Evaluating Berubicin in Advance of the Pre-Planned Interim Analysis of Efficacy (Issuer Direct) - P2 | N=210 | NCT04762069 | Sponsor: CNS Pharmaceuticals, Inc. | "CNS Pharmaceuticals, Inc...announced the presentation of updated safety data from the ongoing potentially pivotal study evaluating Berubicin, the Company's novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier, in a poster presentation at the SNO 28th Annual Meeting, held November 15-19, 2023 in Vancouver, Canada....All reported adverse events for both arms are shown for all grades and grades 3-5. These were similar, including the more severe events in the higher grades. The adverse events occurring in more than 10% of patients and/or that were considered treatment-related, are shown for all grades as well as grades 3-5, and overall were relatively similar in the Berubicin and Lomustine arms."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor