TPI 287 / Cortice Biosci, CNS Pharma - LARVOL DELTA

TPI 287, which in combination with Bevacizumab (BEV) has shown activity in patients with glioblastoma (GBM) after prior therapy, to be evaluated in a Phase 2 trial as well as in other CNS diseases (WFNOS 2025) - "Given the unique properties of TPI 287 to avoid blood brain barrier efflux, its safety profile, and demonstration of efficacy in GBM, several possibilities for further development, including strategies for metastatic tumors, e.g. triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) that are sensitive to these therapies and evaluation in a combination with radiation therapy, which is a standard of care for metastatic disease is being planned. We are also exploring the effect of this drug in a panel of pediatric brain tumors for feasibility of future clinical studies"

Clinical • Combination therapy • P2 data • Brain Cancer • Breast Cancer • CNS Disorders • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • MGMT

TPI 287, which in combination with Bevacizumab (BEV) has shown activity in patients with glioblastoma (GBM) after prior therapy, to be evaluated in a Phase 2 trial as well as in other CNS diseases (SNO 2025) - "Given the unique properties of TPI 287 to avoid blood brain barrier efflux, its safety profile, and demonstration of efficacy in GBM, several possibilities for further development, including strategies for metastatic tumors, e.g. triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) that are sensitive to these therapies and evaluation in a combination with radiation therapy, which is a standard of care for metastatic disease is being planned. We are also exploring the effect of this drug in a panel of pediatric brain tumors for feasibility of future clinical studies"

Clinical • Combination therapy • P2 data • Brain Cancer • Breast Cancer • CNS Disorders • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • 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

TPI 287: Late Stage, Novel Blood Brain Barrier Permeable Abeotaxane for Treatment of Brain Malignancies (ACCESS Newswire) - "In a Phase 1 trial treating glioblastoma patients with TPI 287 in combination with bevacizumab (Avastin), the efficacy data included 3 Complete Responses and 9 Partial Responses out of 23 evaluable patients. These results are from an early-stage trial and may not be indicative of results in larger, controlled studies. CNS Pharmaceuticals plans to engage the FDA and obtain feedback on the design of a study potentially focused on the registration of TPI 287 in recurrent GBM in early 2026."

FDA event • P1 data • Glioblastoma

CNS Pharmaceuticals Participates in Virtual Investor CEO Connect Segment (CNS Pharma Press Release) - "CNS Pharmaceuticals, Inc...announced that John Climaco, CEO of CNS Pharmaceuticals recently participated in a Virtual Investor CEO Connect segment....As part of this segment, Mr. Climaco provided an overview of CNSP's lead program, TPI 287, and discussed key insights from his recent attendance at the Longwood Healthcare Leaders Spring 2025 Meeting in Cambridge, MA."

Clinical • Glioblastoma

CNS Pharmaceuticals Announces Virtual Investor KOL Connect Segment Discussing Glioblastoma Multiforme GBM and Lead Product Candidate TPI 287 (CNS Pharma Press Release) - "CNS Pharmaceuticals, Inc...announced the release of a Virtual Investor KOL Connect segment featuring Dr. Erin Dunbar, a founding physician of the Brain Tumor Center and Director of Neuro-Oncology at Piedmont Atlanta Hospital, who specializes in the comprehensive care of brain and spine tumor patients who are battling both primary and metastatic tumors...As part of the segment, Dr. Dunbar discussed the patient journey and current treatment landscape for Glioblastoma Multiforme and CNS Pharma's lead product candidate, TPI 287, and its potential as a treatment for GBM as well as for future indications in metastatic tumors."

Clinical • CNS Tumor • Glioblastoma

CNS Pharmaceuticals' Chief Medical Officer, Sandra Silberman, MD, PhD to Present at the 2025 Brain Tumor Biotech Summit (Yahoo Finance) - "In person presentation today, Thursday, June 5th at 9:30 AM ET to discuss Company's lead program, TPI 287, in development for treatment of glioblastoma multiforme (GBM)."

Clinical data • Glioblastoma

CNS Pharmaceuticals Reports First Quarter 2025 Financial Results and Provides Corporate Update (CNS Pharma Press Release) - "Advancing development strategy for lead program TPI 287 to commence Phase 2 study around year end 2025 for treatment of glioblastoma multiforme (GBM); CNS Pharmaceuticals plans to engage the FDA and obtain feedback on the design of a study potentially focused on the registration of TPI 287 in recurrent GBM in 2025."

New P2 trial • Glioblastoma

CNS Pharmaceuticals Acquires Orphan Drug Designation for Novel Late Stage Abeotaxane TPI 287 (CNS Pharma Press Release) - "CNS Pharmaceuticals, Inc...announced the successful transfer from Cortice Biosciences, Inc. of Orphan Drug Designation for TPI 287....Additionally, the Company announced the release of a "What This Means" segment to discuss the Orphan Drug Designations for TPI 287."

Orphan drug • Glioblastoma

CNS Pharmaceuticals Reports Full Year 2024 Financial Results (CNS Pharma Press Release) - "CNS Pharmaceuticals plans to engage the FDA and obtain feedback on the design of a study potentially focused on the registration of TPI 287 in recurrent GBM in 2025."

FDA event • Glioblastoma

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 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 Expands Pipeline with In License of Late Stage Novel Potential Blood Brain Barrier Permeable Abeotaxane for Treatment of Brain Malignancies (CNS Pharma Press Release) - "CNS Pharmaceuticals, Inc... announced that it has entered into an exclusive license agreement with Cortice Biosciences, Inc. ('Cortice'). The Company will host a live webcast presentation to discuss the transaction on Tuesday, July 30, 2024 at 8:30 AM ET....Under the terms of the Agreement, CNS Pharmaceuticals has obtained an exclusive license and the intellectual property rights to TPI 287, a potentially blood brain barrier permeable microtubule inhibitor, currently in development for the treatment of GBM, in exchange for an upfront payment of 616,698 shares of the Company's common stock, as well as the possibility of future success-dependent milestone payments of cash or the Company's common stock to Cortice....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."

Licensing / partnership • New trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Phase 1 trial of TPI 287, a microtubule stabilizing agent, in combination with bevacizumab in adults with recurrent glioblastoma. (PubMed, Neurooncol Adv) - "The optimal phase 2 dose was determined to be 200 mg/m2. TPI 287 can be safely combined with BEV for the treatment of rGBM and preliminary efficacy supports further investigation of this combination."

Combination therapy • Journal • P1 data • Brain Cancer • CNS Tumor • Fatigue • Glioblastoma • Oncology • Pain • Solid Tumor

Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review. (PubMed, Int J Mol Sci) - "The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile. Moreover, the domain of behavioral symptoms was found to be less investigated, thus prompting new prospective studies with homogeneous design. PROSPERO registration: CRD42023393456."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry

Dose-Escalation Study of TPI 287 + Avastin Followed by Randomized Study of the Same Versus Avastin for Glioblastoma (clinicaltrials.gov) - P1/2 | N=92 | Suspended | Sponsor: Cortice Biosciences, Inc. | Trial completion date: May 2023 ➔ May 2025 | Trial primary completion date: Nov 2022 ➔ Nov 2024

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

The CNS-penetrating taxane drug TPI 287 potentiates antiglioma activity of the AURKA inhibitor alisertib in vivo. (PubMed, Cancer Chemother Pharmacol) - "Results suggest that apoptosis is the dominant mechanism of potentiation of GBM growth inhibition by alisertib + TPI 287, in part through effects on Bcl-2 family proteins, providing a rationale for further laboratory testing of an AURKA inhibitor plus TPI 287 as a potential therapy against GBM."

IO biomarker • Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • ANXA5 • BCL2

Final results from the dose-escalation stage of a phase 1/2 trial of TPI 287, a brain penetrable microtubule inhibitor, plus bevacizumab in patients with recurrent glioblastoma. (ASCO 2017) - P1/2; "TPI 287 in combination with BEV is safe and well tolerated at doses up to 220 mg/m2. Final survival results from the Phase 1 portion of this study compare favorably with historical controls and support further investigation of TPI 287 plus BEV for treatment of recurrent GBM."

P1/2 data • Biosimilar

Protective effect and possible mechanism of arctiin on broilers challenged by Salmonella pullorum. (PubMed, J Anim Sci) - "The in vivo trial was randomly assigned to 6 groups: non-infected control group (NC) and positive control group (PC) received a basal diet; TET group, received a basal diet supplemented with 100 mg/kg chlortetracycline; ARC100, ARC200 and ARC400 groups received a basal diet containing 100, 200, 400 mg/kg ARC, respectively. Metabonomics analysis revealed that ARC can restrain the formation of the biofilm by affecting a variety of metabolic pathways of S. pullorum. Therefore, dietary supplementation of 200 mg/kg ARC might be a potentially way to substitute antibiotics to control S. pullorum infection in broilers."

Journal • Infectious Disease • CXCL8 • IFNG • IL10

Randomized Efficacy Study of TPI 287 to Treat Primary Refractory or Early Relapsed Neuroblastoma (clinicaltrials.gov) - P1/2; N=14; Terminated; Sponsor: Giselle SaulnierSholler; N=132 ➔ 14

Clinical • Combination therapy • Enrollment change • Neuroblastoma • Oncology • Solid Tumor • MRI

[VIRTUAL] The CNS Penetrating Taxane TPI 287 and the AURKA Inhibitor Alisertib Improve Survival In Vivo (SNO 2020) - "At 4 weeks the alisertib and TPI 287 groups showed a trend toward decreased tumor volume with a significant decrease in the combination therapy group. This data supports the potential use of this combination therapy in human trials."

Glioblastoma • Oncology • Solid Tumor • AURKA

Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome: A Randomized Clinical Trial. (PubMed, JAMA Neurol) - P1 | "The ability to reveal different tau therapeutic effects in various tauopathy syndromes suggests that basket trials are a valuable approach to tau therapeutic early clinical development. ClinicalTrials.gov identifiers: NCT019666666 and NCT02133846."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy

Dose-Escalation Study of TPI 287 + Avastin Followed by Randomized Study of the Same Versus Avastin for Glioblastoma (clinicaltrials.gov) - P1/2; N=92; Suspended; Sponsor: Cortice Biosciences, Inc.; Trial completion date: Mar 2019 ➔ May 2023; Trial primary completion date: Mar 2019 ➔ Nov 2022

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Phase 1/2 trial of bevacizumab plus TPI 287, a brain penetrable anti-microtubule agent, in patients with recurrent glioblastoma. (ASCO 2016) - P1/2, N=24; NCT01933815; Sponsor: Cortice Biosciences; "Among 20 patients evaluable for response, ORR was 60% (12/20; 3 complete, 9 partial). The median and 6-month PFS were 5.5 mo. [95% C.I. 4.1-6.9] and 37%, respectively. Median and 1-year OS were 12.9 mo. [95% C.I. 10.9-17.9] and 63%, respectively, after 20.1 mo. median follow-up."

P1/2 data • Biosimilar • Oncology

Safety Study of TPI-287 to Treat CBS and PSP (clinicaltrials.gov) - P1; N=44; Completed; Sponsor: University of California, San Francisco; Active, not recruiting ➔ Completed; Trial completion date: Mar 2019 ➔ Sep 2019; Trial primary completion date: Dec 2018 ➔ Sep 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Hematological Disorders • Movement Disorders • Progressive Supranuclear Palsy