sabizabulin (VERU-111) / Veru Inc, Valeo Pharma - LARVOL DELTA

VERU-111 as a promising therapeutic for colorectal cancer (IMMUNOLOGY 2025) - "We also noticed induction of apoptosis in tumors of VERU-111 treated mice, as evidenced by upregulation of apoptotic markers BAX and cleaved caspase-3. These findings suggest that VERU-111 effectively reduces tumor burden, induces effector T cells and apoptosis, as well as modulates myeloid cells expressing PD-L1 for suppression of CRC and offers promising insights to explore it further as a therapy for CRC.Keywords: Animals Rodent; Cells Dendritic Cells T Cells; Processes Apoptosis; Tissues Spleen and Lymph Nodes"

IO biomarker • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BAX • CASP3 • CD8 • CXCR3 • PD-L1

A p53-deficient, PTK2/cMyc-driven ovarian cancer mouse model for preclinical drug discovery (AACR 2025) - "Mice intrabursally injected with PC53K cells exhibited bloody ascites, aggressive primary tumor growth and widespread metastasis, which faithfully recapitulates the phenotypes of human ovarian serous adenocarcinoma. Additionally, the paclitaxel-resistant PC53K/TxR cell line shows significant higher IC50 for paclitaxel than PC53K cell line, indicating it is a valuable tool for studying OC chemoresistance. Compounds VERU-111 and SB-216 significantly inhibited tumor growth and metastasis in orthotopic OC mouse models by overcoming chemoresistance."

Preclinical • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • MYC • PTK2 • TP53

Veru Reports Fiscal 2025 First Quarter Financial Results and Clinical Program Progress (GlobeNewswire) - "The topline results of the separate blinded Phase 2b extension clinical study are expected in the second quarter of calendar 2025... Veru is currently developing a novel, patentable, modified release formulation for enobosarm...The drug product formulation is currently in animal trials and is anticipated to be available for a Phase 1 bioavailability clinical trial during the first half of calendar 2025...Veru had a pre-IND meeting with the FDA Division of Cardiology and Nephrology Center for Drug Evaluation and Research on December 26, 2024...The indication for discussion was the use of sabizabulin to slow progression or promote regression of atherosclerotic disease in patients with a history of coronary artery disease...The chronic nonclinical toxicology studies are expected to be completed and a new IND for the proposed indication is planned to be submitted by the first half calendar 2026."

IND • New P1 trial • P2b data • Atherosclerosis • Cardiovascular • Obesity

VERU-111, an orally available tubulin inhibitor, suppresses ovarian tumor growth and metastasis. (PubMed, J Pharmacol Exp Ther) - "Colchicine binding site inhibitors (CBSIs) are attractive alternatives to taxanes because they could potentially achieve oral bioavailability and overcome drug resistance associated with the prolonged use of taxanes. SIGNIFICANCE STATEMENT: VERU-111 is an investigational new drug and has comparable efficacy as paclitaxel in suppressing tumor cell proliferation, colony formation, and migration in ovarian cancer models in vitro and has potent in vivo antitumor and antimetastatic activity in an orthotopic ovarian cancer mouse model. VERU-111 has low systemic toxicity and, unlike paclitaxel, is orally bioavailable and is not a substrate for the major drug efflux transporters, making it a promising and attractive alternative to taxane-based therapy."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Sabizabulin Ameliorates Kidney Fibrosis by Inhibition of Myofibroblast-Specific Beta Tubulin 3 (KIDNEY WEEK 2024) - "Sabizabulin was shown to be effective to ameliorate kidney fibrosis in virto and in vivo. It could be a potential treatment option for CKD."

Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • TGFB1 • TUBB3

VERU-111, an Orally Available Tubulin Inhibitor, Suppresses Ovarian Tumor Growth and Metastasis. (PubMed, J Pharmacol Exp Ther) - "Colchicine binding site inhibitors (CBSIs) are attractive alternatives to taxanes because they could potentially achieve oral bioavailability and overcome drug resistance associated with the prolonged use of taxanes. Significance Statement VERU-111 is an investigational new drug and has comparable efficacy as paclitaxel in suppressing tumor cell proliferation, colony formation, and migration in ovarian cancer models in vitro and has potent in vivo anti-tumor and anti-metastatic activity in an orthotopic ovarian cancer mouse model. VERU-111 has low systemic toxicity and, unlike paclitaxel, is orally bioavailable and is not a substrate for the major drug efflux transporters, making it a promising and attractive alternative to taxane-based therapy."

Journal • Colorectal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Biological activity of a stable 6-aryl-2-benzoyl-pyridine colchicine-binding site inhibitor, 60c, in metastatic, triple-negative breast cancer. (PubMed, Cancer Lett) - "TNBC therapy includes a combination of cytotoxic chemotherapies, including microtubule-targeting agents (MTAs) like paclitaxel (taxane class) or eribulin (vinca class); however, there are currently no FDA-approved MTAs that bind to the colchicine-binding site. In contrast, VERU-111 preferentially inhibited liver metastases and lung metastasis repression was similar. Together, these results position 60c as an additional promising CBSI for TNBC therapy, particularly for patients with TxR disease."

Journal • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PGR

Targeting the colchicine binding site in tubulin for cancer therapy (ACS-Sp 2024) - "Tubulin inhibitors including the taxanes Taxol® (paclitaxel) or Taxotere® (docetaxel) are widely used chemotherapeutic drugs in treating a variety of types of cancers. The investigational new drug from this ongoing project, sabizabulin, has been under multiple clinical trials for metastatic cancer and for viral infections. X-ray crystal structure of tubulin protein in complex with the colchicine site inhibitor SHIP-216"

Infectious Disease • Oncology • Pain

Oral Sabizabulin for High-Risk, Hospitalized Adults with Covid-19: Interim Analysis. (PubMed, NEJM Evid) - "report on an interim analysis of a phase 3 randomized controlled trial of the orally available novel microtubule disruptor sabizabulin for severe Covid-19. They find a reduction in 60-day mortality from 45.1% to 20.2%."

Clinical • Journal • P3 data • Infectious Disease • Novel Coronavirus Disease

A novel stable 6-aryl-2-benzoyl-pyridine colchicine-binding site inhibitor targeting microtubules (60c) is effective against taxane-resistant, metastatic breast cancer (SABCS 2023) - "TNBC therapy relies on a combination of systemically administered chemotherapies, including microtubule-targeting agents (MTAs) like paclitaxel (taxane class) or eribulin (vinca class); however, there are currently no FDA approved MTAs that bind to the colchicine-binding site. 60c shows improved potency compared to sabizabulin against taxane-sensitive and TxR TNBC models, inhibiting proliferation and clonogenicity at low nanomolar concentrations, and inducing apoptosis in a dose-dependent manner. In vivo, 60c therapy significantly suppressed primary tumor growth and lung metastasis in an orthotopic MDA-MB-231-TxR xenograft model without gross toxicity, and with equivalent efficacy to combrestatin A4 phosphate (CA-4P), another CBSI in clinical trials. In the taxane-refractory HCI-10-Luc2 PDX model, 60c significantly suppressed both the growth of the primary tumor (by ~3.5 fold) and the expansion of pre-established axillary metastases (by ~26 fold) whereas paclitaxel had..."

Metastases • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

MitoCur-1 induces ferroptosis to reverse vemurafenib resistance in melanoma through inhibition of USP14. (PubMed, Pigment Cell Melanoma Res) - "We previously tested the combination regimen of tubulin inhibitor VERU-111 with vem, as well as USP14 selective inhibitor b-AP15 in combination with vem, both of which have showed profound therapeutic effects in overcoming vem resistance in vitro and in vivo. Interestingly, overexpression of USP14 antagonized all the ferroptosis cascade events induced by MitoCur-1, therefore, we conclude that MitoCur-1 induces ferroptosis through inhibition of USP14. We believe that by inhibition of USP14, vem resistance can be reversed and will finally benefit melanoma patients in future."

Journal • Melanoma • Oncology • Solid Tumor • Targeted Protein Degradation • BRAF • GPX4 • SKP2 • SLC7A11 • USP14

Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform. (PubMed, Sci Rep) - "Sabizabulin was highly toxic at concentrations only 5 times higher than C and led to a mean mortality of 20% at C. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc_dataapp/main/CoVasc_DataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases."

Adverse events • Journal • Cardiovascular • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

VERACITY: Efficacy Evaluation of VERU-111 for mCRPC in Patients Who Have Failed at Least One Androgen Receptor Targeting Agent (clinicaltrials.gov) - P3 | N=105 | Terminated | Sponsor: Veru Inc. | N=245 ➔ 105 | Trial completion date: Sep 2024 ➔ May 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2024 ➔ May 2023; Administrative reasons

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1b/2 | N=80 | Terminated | Sponsor: Veru Inc. | N=58 ➔ 80 | Completed ➔ Terminated; Administrative decision

Enrollment change • Metastases • Trial termination • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Molecular structure, spectral analysis and chemical activity of sabizabulin: A computational study. (PubMed, J Mol Graph Model) - "Our findings provide valuable insights into the spectroscopic properties of sabizabulin, highlighting its potential therapeutic applications. Our work aims to explore future research directions that could expand the understanding of sabizabulin's actions and enhance its applicability in medical treatments."

Journal • Oncology

Optimized synthesis of anti-COVID-19 drugs aided by retrosynthesis software. (PubMed, RSC Med Chem) - "Favipiravir is one of the potential anti-COVID-19 drugs, but its original synthetic route with 7 harsh steps gives a low product yield (0.8%) and has a high cost ($68 per g). We also used the same strategy to optimize the synthesis of sabizabulin. We anticipate that these synthetic routes will contribute to the prevention and treatment of COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease

Sabizabulin - an unprecedented yet effective drug against COVID-19. (PubMed, J Pak Med Assoc) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1b/2 | N=58 | Completed | Sponsor: Veru Inc. | Active, not recruiting ➔ Completed | N=41 ➔ 58

Enrollment change • Metastases • Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Antiandrogens for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials. (PubMed, J Med Virol) - "However, on subgroup analysis, only proxalutamide/enzalutamide and sabizabulin were found to significantly reduce mortality (RR 0.22, 95% CI: 0.16-0.30 and RR 0.42, 95% CI: 0.26-0.68, respectively), while aldosterone receptor antagonists and antigonadotropins did not show any benefit...Antiandrogens also reduced hospitalizations and the duration of hospital stay, and improved recovery rates. Proxalutamide and sabizabulin may be effective against COVID-19, however, further large-scale trials are needed to confirm these findings."

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Sabizabulin shows anti-cancer efficacy in HER2+ breast cancer and novel sabizabulin derivatives overcome paclitaxel-resistance in triple negative breast cancer (AACR 2023) - "Preferred frontline treatment relies on anti-HER2 therapies, such as trastuzumab and pertuzumab, combined with microtubule inhibitors, such as taxanes. While sabizabulin shows promising results for treatment in HER2+ breast cancer, we further optimized the structure of sabizabulin to create a new class of anti-cancer molecules: 40a, CH-2-77, and 60c. Based on in vitro data, 60c showed higher potency in HER2+ breast cancer cell lines and was chosen as the lead compound to further study in a paclitaxel-resistant triple negative breast cancer in vivo study where it was able to effectively inhibit primary tumor growth compared to the vehicle group."

Clinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Efficacy Evaluation of Sabizabulin Monotherapy Versus Active Control for Treatment of ER+HER2- Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Veru Inc. | N=200 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Metastases • Monotherapy • Trial withdrawal • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

VERACITY: Efficacy Evaluation of VERU-111 for mCRPC in Patients Who Have Failed at Least One Androgen Receptor Targeting Agent (clinicaltrials.gov) - P3 | N=245 | Active, not recruiting | Sponsor: Veru Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Sabizabulin has both cytotoxic and cytostatic activity in Phase 1b/2 clinical of men with metastatic castration resistant prostate cancer who progressed on androgen receptor targeting agents (EAU 2022) - "11 (37%) were previously treated with enzalutamide or apalutamide and 8 (27%) with abiraterone as single agents. In this analysis, sabizabulin has demonstrated not only cytotoxic, but also significant cytostatic activity with similar responses in men that have progressed on a single or multiple ARTA agents. Sabizabulin is a novel agent with the potential provide men with mCRPC a well-tolerated chronic treatment cytostatic option after progressing on an ARTA and is being tested in the open Phase 3 VERACITY trial."

Clinical • P1/2 data • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • AR

VALEO PHARMA ANNOUNCES FILING OF A NEW DRUG SUBMISSION-COVID 19 WITH HEALTH CANADA FOR SABIZABULIN FOR THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS (Canada Newswire) - "Valeo Pharma Inc...announced today that Health Canada has accepted for review Veru's New Drug Submission ('NDS-CV') for sabizabulin for COVID-19. Sabizabulin is a novel dual antiviral and anti-inflammatory agent being developed for the treatment of hospitalized moderate to severe COVID-19 adult patients at high risk for acute respiratory distress syndrome (ARDS) and death."

Canadian regulatory • Infectious Disease • Novel Coronavirus Disease

"What is essential for saving lives, is effective treatments for the severly ill patients, e.g Sabizabulin. https://t.co/Ed2L5IXCFu" (@Yochana42437421)

Clinical