On September 8, 2026 Veru Inc. (NASDAQ: VERU) reported new preclinical data showing that sabizabulin can overcome drug resistance to daraxonrasib (RASONQUE1 Revolution Medicines) with potent anticancer efficacy (IC50=18.2nM) in daraxonrasib resistant human pancreatic cancer cell line which is a drug concentration that can be achieved with current sabizabulin human dosing with good safety.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Based on the new, positive preclinical data, and the previous preclinical and clinical sabizabulin studies, the Company will advance sabizabulin into a planned Phase 2 clinical trial for metastatic KRAS-driven pancreatic cancer progression that has become resistant to the recent FDA approved daraxonrasib.
New preclinical data results: Sabizabulin demonstrated potent anticancer activity against KRAS-driven metastatic cancer cell lines that were resistant to daraxonrasib (August 2026)
Preclinical studies were performed using a 2D proliferation assay to evaluate the efficacy of sabizabulin in parental and daraxonrasib resistant KRAS driven pancreatic cancer cell line AsPC-1 (G12D KRAS mutation) and colon cancer HCT-116 cell line (G13D KRAS mutation). It was confirmed that the reason for daraxonrasib resistance was the reactivation of the KRAS signaling pathway in both pancreatic and colon daraxonrasib resistant cell lines. The resistance index (RI) was calculated, which is the ratio of drug concentration required to inhibit 50% cell growth (IC50) in resistant cell line compared to its parental (sensitive) cell line. The resistance index represents the fold-change in drug tolerance of the resistant cell line compared to its sensitive, parental cell line. An RI greater than 1 indicates resistance, while an RI below 1 indicates increased sensitivity to the drug.
Like daraxonrasib, sabizabulin had potent anticancer activity for both pancreatic cancer and colon cancer parental cell lines regardless of the type of KRAS mutation. As expected, the daraxonrasib resistant cell lines were resistant to daraxonrasib with a RI of 68 for pancreatic cancer cell line and RI of >128 for colon cancer cell line. In contrast, daraxonrasib resistant pancreatic cancer cell lines became more sensitive (collateral sensitivity) to sabizabulin with a RI of 0.25 and daraxonrasib resistant colon cell line retained sensitivity to sabizabulin with a RI of 1. In summary, sabizabulin retained highly potent anticancer efficacy in daraxonrasib resistant pancreatic and colon cancer cell lines that had reactivation of KRAS signaling pathway as the mechanism for drug resistance to daraxonrasib. These preclinical data may also support sabizabulin as a treatment of daraxonrasib resistant cancer types beyond pancreatic cancer.
"The recent FDA approval of Revolution Medicines’ daraxonrasib was a major breakthrough in the treatment of KRAS-driven metastatic pancreatic cancer," said Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer of Veru Inc. "Unfortunately, resistance to daraxonrasib occurs as the median time to cancer progression was 7.2 months in patients receiving daraxonrasib. The primary mechanism that leads to daraxonrasib reactivation is reactivation of the KRAS signaling pathway. As sabizabulin targets downstream components of the KRAS signaling pathway, we explored and confirmed in recently completed preclinical studies that sabizabulin has the potential to treat metastatic pancreatic cancer that has become resistant to daraxonrasib. This exciting new development and the importance of this large unmet medical need compel us to pursue this novel sabizabulin oncology indication. With the goal of maximizing Veru shareholder value, we have made the strategic decision to advance sabizabulin into a Phase 2b clinical trial. Consequently, we will no longer be exploring sabizabulin for the treatment of chronic inflammation related to atherosclerotic cardiovascular disease. The Company controls global development and commercialization rights to sabizabulin with issued patent protection until 2043."
Dr. Steiner added: "Our enobosarm obesity program is completely on track. The Phase 2b PLATEAU clinical trial is fully enrolled, and we expect the interim analysis, a near term milestone, in calendar Q1 2027. We entered into a clinical supply agreement with Novo Nordisk2, and we now have an issued US patent for enobosarm with semaglutide with expiry in late 2044."
"Sabizabulin represents a compelling candidate for Phase 2 evaluation following daraxonrasib treatment, based on its profile as an oral, targeted agent with a novel microtubule binding mechanism and its ability to downregulate TUBB3 and other downstream effectors of the KRAS signaling pathway. The rationale is further strengthened by reassuring safety findings from a previous Phase 1b/2 study in 80 patients, as well as preclinical data evidence that daraxonrasib resistance may potentiate sensitivity to sabizabulin. Together, these findings support clinical investigation of sabizabulin as a rational post-daraxonrasib strategy," said Daniel King, M.D., Ph.D., Medical Oncologist and Director of Research and Development for Genomic Medicine at Northwell Health.
Sabizabulin is a clinical stage oncology drug candidate that has a favorable safety profile with promising preliminary anticancer activity
Sabizabulin’s first-in-man study was a Phase 1/2b clinical trial evaluating safety and efficacy of sabizabulin in advanced metastatic prostate cancer (Markowski et al. Clin Cancer Res 28:2789-2795, 2022). We believe positive efficacy and safety clinical data from this Phase 1b/2 first-in-man clinical study of sabizabulin monotherapy conducted in 80 patients with heavily pretreated metastatic castration resistant and taxane resistant prostate cancer support the translational potential of sabizabulin treatment for daraxonrasib resistant metastatic pancreatic cancer.
The Phase 1b portion utilized a 3+3 dose escalation design with escalating daily oral doses of 4.5 mg—81 mg (7 days on drug/14 days off per 21-day cycle, which was then expanded to daily dosing). The Phase 1b portion included 39 metastatic castration resistant cancer patients that were treated with one or more novel androgen receptor targeting agents. Most patients had bone-only disease (55%) with an additional 21% having both lymph node and bone involvement with 23% of patients with prior taxane-based chemotherapy. The Phase 2 portion tested a daily dose of 63 mg in 41 heavily pretreated similar patient population, but with no prior chemotherapy. Efficacy was assessed using PCWG3 and RECIST 1.1 criteria.
The maximum tolerated dose was not defined in the Phase 1b as all doses tested were well tolerated. The recommended Phase 2 dose was set at 63 mg/day. The most common adverse events (>10% frequency) at the 63 mg oral daily dosing (combined Phase 1b/2 safety data) were predominantly Grade 1-2 events. Grade ≥3 events included diarrhea (7.4%), fatigue (5.6%) and ALT/AST elevations (5.6% and 3.7%, respectively). Neurotoxicity and neutropenia were not observed at these dosage levels.
Efficacy data in patients treated with ≥1 continuous cycle (21 days) of 63 mg or higher had a Kaplan-Meier median radiographic progression-free survival that was estimated to be 11.4 months with durable responses lasting greater than 12 months, occurring in 14.5% (n=55) patients. The objective response rate was 20.7% in patients with measurable disease and durable responses lasting greater than 2.75 years were observed. Compared to historical controls, the radiographic progression-free survival in similar patients was only 3.6 months and objective response rate was 2% with an alternative androgen receptor blocking agent (deBono J NEJM 382:2091, 2020). This Phase 1b/2 clinical trial had a favorable safety profile with promising preliminary antitumor activity and demonstrated that chronic oral daily dosing of sabizabulin was feasible up to 3 years.
Next steps
Preclinical studies including in daraxonrasib resistant pancreatic and colon cell lines and promising clinical data from Phase 1b/2 clinical trial conducted in metastatic castration resistant and taxane resistant prostate cancer support the translational potential of sabizabulin against daraxonrasib resistant metastatic pancreatic cancer. Accordingly, the Company plans to pursue a Phase 2b clinical study to evaluate the efficacy and safety of sabizabulin in patients who have metastatic pancreatic cancer progression while receiving treatment with daraxonrasib (RASONQUE). We will first seek regulatory clarity from the FDA through a preIND meeting in calendar Q4 2026 to better understand the scope of the clinical trial. We believe these recent developments will create greater shareholder value.
(Press release, Veru, SEP 8, 2026, View Source [SID1234670630])