Background: Sabizabulin is a novel oral cytoskeleton disruptor being developed for use in metastatic castration resistant prostate cancer (mCRPC). A phase 1b/2 clinical study was conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC resistant to androgen receptor targeting agents (ARTAs). Methods: The phase 1b portion of the study in 39 men utilized escalating and expanding dose and duration. The phase 2 portion studied 41 men with mCRPC at the recommended phase 2 dose (RP2D) of 63 mg daily. Based upon the phase 1b/2 data, sabizabulin appears to have both cytotoxic and cytostatic activity. A analysis was conducted evaluating the best clinical response (BCR) defined as either an objective response assessed by PCWG3 criteria and/or stable disease defined as ≥5 cycles (≥15 weeks) of continuous treatment. Results: Of the combined 80 patients in the phase 1b/2 portions of the study, the BCR was 37.5% (30/80) and 5 of the responders remain on study with the longest being treated for more than 30 months. Of the patients with measurable disease at study entry, the BCR was 59% (17/29). Prior to study entry, 11/30 (37%) of those with a BCR had previously been treated with and subsequently progressed on a minimum of 2 ARTAs. The remaining 19/30 (63%) had progressed on a single ARTA agent. 11 (37%) were previously treated with enzalutamide or apalutamide and 8 (27%) with abiraterone as single agents. 8 (27%) received enzalutamide and abiraterone and 3 (10%) patients received more than two ARTAs. As described previously, the safety profile continues to be favorable with no clinically relevant neutropenia or neurotoxicity. Conclusions: 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 trial information: NCT03752099.