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DRUG:

sabizabulin (VERU-111)

i
Other names: VERU-111, ABI-231 oral, VERU 111, APP-111, bisindole, V-111
Company:
Valeo Pharma, Veru Inc
Drug class:
α-tubulin inhibitor, β-tubulin inhibitor
Related drugs:
4ms
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
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BRAF (B-raf proto-oncogene) • GPX4 (Glutathione Peroxidase 4) • SLC7A11 (Solute Carrier Family 7 Member 11) • SKP2 (S-phase kinase-associated protein 2) • USP14 (Ubiquitin Specific Peptidase 14)
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BRAF V600E • BRAF V600 • SLC7A11 expression
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Zelboraf (vemurafenib) • sabizabulin (VERU-111)
6ms
To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=80, Terminated, Veru Inc. | N=58 --> 80 | Completed --> Terminated; Administrative decision
Enrollment change • Trial termination • Metastases
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
6ms
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, 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 • Trial completion date • Trial termination • Trial primary completion date • Metastases
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AR (Androgen receptor)
|
enzalutamide capsule • abiraterone acetate • sabizabulin (VERU-111)
9ms
Trial completion • Enrollment change • Metastases
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
1year
Enrollment change • Trial withdrawal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
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everolimus • fulvestrant • exemestane • sabizabulin (VERU-111)
1year
Enrollment closed • Metastases
|
AR (Androgen receptor)
|
enzalutamide capsule • abiraterone acetate • sabizabulin (VERU-111)
1year
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
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HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression
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Herceptin (trastuzumab) • paclitaxel • Perjeta (pertuzumab) • sabizabulin (VERU-111)
1year
Final Analysis of the Phase 1b/2 Study Of Sabizabulin in Men with Metastatic Castration Resistant Prostate Cancer who Progressed on an Androgen Receptor Targeting Agent (WSAUA 2022)
This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with significant preliminary cytotoxic and cytostatic antitumor activity. These data support the ongoing Phase 3 VERACITY trial of sabizabulin in men with mCRPC who have progressed on an androgen receptor targeting agent.
P1/2 data • Metastases
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over1year
Efficacy Evaluation of Sabizabulin Monotherapy Versus Active Control for Treatment of ER+HER2- Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=200, Not yet recruiting, Veru Inc. | Trial completion date: Feb 2024 --> May 2024 | Trial primary completion date: Dec 2023 --> Mar 2024
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
|
everolimus • fulvestrant • exemestane • sabizabulin (VERU-111)
over1year
To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=41, Active, not recruiting, Veru Inc. | Trial completion date: Nov 2022 --> Apr 2023 | Trial primary completion date: Sep 2022 --> Feb 2023
Trial completion date • Trial primary completion date • Metastases
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over1year
Sabizabulin, a Potent Orally Bioavailable Colchicine Binding Site Agent, Suppresses HER2+ Breast Cancer and Metastasis. (PubMed, Cancers (Basel))
Current frontline therapy for HER2+ metastatic breast cancer relies on targeted antibodies, trastuzumab and pertuzumab, combined with microtubule inhibitors in the taxane class (paclitaxel or docetaxel). In vivo, sabizabulin inhibits breast tumor growth in the BT474 (ER+/PR+/HER2+) xenograft model and a HER2+ (ER-/PR-) metastatic patient-derived xenograft (PDX) model, HCI-12. We demonstrate that sabizabulin is a promising alternative agent to target tubulin in HER2+ breast cancer with similar anti-metastatic efficacy to paclitaxel, but with the advantage of oral bioavailability and lower toxicity than taxanes.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
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Herceptin (trastuzumab) • paclitaxel • docetaxel • Perjeta (pertuzumab) • sabizabulin (VERU-111)
over1year
Final analysis of the phase Ib/II study of sabizabulin in men with metastatic castration-resistant prostate cancer who progressed on an androgen receptor targeting agent (ESMO 2022)
Conclusions This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with significant preliminary cytotoxic and cytostatic antitumor activity. These data support the ongoing phase 3 VERACITY trial of sabizabulin in men with mCRPC who have progressed on an androgen receptor targeting agent.
P1/2 data
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over1year
A Phase 1b/2 Study of Sabizabulin, a Novel Oral Cytoskeleton Disruptor, in Men With Metastatic Castration-Resistant Prostate Cancer with Progression on an Androgen Receptor Targeting Agent. (PubMed, Clin Cancer Res)
This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with preliminary antitumor activity. These data support the ongoing Phase 3 VERACITY trial of sabizabulin in men with mCRPC.
P1/2 data • Clinical Trial,Phase II • Journal
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
almost2years
Final analysis of the phase 1b/2 study of sabizabulin in men with metastatic castration-resistant prostate cancer who progressed on an androgen receptor targeting agent. (ASCO 2022)
This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with significant preliminary cytotoxic and cytostatic antitumor activity. These data support the ongoing Phase 3 VERACITY trial of sabizabulin in men with mCRPC who have progressed on an androgen receptor targeting agent.
P1/2 data
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
almost2years
Phase 3 VERACITY clinical study of sabizabulin in men with metastatic castration-resistant prostate cancer who have progressed on an androgen receptor targeting agent. (ASCO 2022)
mCRPC that has progressed following ARTAs and prior to taxane chemotherapy, remains an urgent unmet medical need for patients with advanced disease. Sabizabulin is an exciting first-in-class agent that may add to the armamentarium for the treatment of mCRPC following progression on ARTA’s.
Clinical • P3 data
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
almost2years
Trial initiation date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
|
everolimus • fulvestrant • exemestane • sabizabulin (VERU-111)
almost2years
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 (AUA 2022)
11 (37%) were previously treated with enzalutamide or apalutamide and 8 (27%) with abiraterone as single agents. 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 • P1/2 data
|
AR (Androgen receptor)
|
enzalutamide capsule • abiraterone acetate • Erleada (apalutamide) • sabizabulin (VERU-111)
almost2years
To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=41, Active, not recruiting, Veru Inc. | Trial completion date: Apr 2022 --> Nov 2022 | Trial primary completion date: Feb 2022 --> Sep 2022
Trial completion date • Trial primary completion date
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
2years
Enrollment change • Trial withdrawal • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER expression
|
Trodelvy (sacituzumab govitecan-hziy) • sabizabulin (VERU-111)
2years
Efficacy Evaluation of Sabizabulin Monotherapy Versus Active Control for Treatment of ER+HER2- Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=200, Not yet recruiting, Veru Inc. | Trial primary completion date: Sep 2023 --> Dec 2023
Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
|
everolimus • fulvestrant • exemestane • sabizabulin (VERU-111)
2years
The role of sabizabulin in phase 1b/2 clinical trials of men with metastatic castration-resistant prostate cancer who progressed on androgen receptor-targeting agents. (ASCO-GU 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
|
AR (Androgen receptor)
|
enzalutamide capsule • abiraterone acetate • Erleada (apalutamide) • sabizabulin (VERU-111)
2years
Phase 3 VERACITY clinical study of sabizabulin in men with metastatic castrate resistant prostate cancer who have progressed on an androgen receptor targeting agent. (ASCO-GU 2022)
Metastatic prostate cancer that has become refractory to newer generation ARTAs and prior to IV chemotherapy, remains an urgent unmet medical need for patients with advanced disease. Sabizabulin is an exciting first-in-class agent that will add to the armamentarium for the treatment of metastatic castration and ARTA resistant prostate cancer.
Clinical • P3 data
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over2years
To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=41, Active, not recruiting, Veru Inc. | Trial completion date: Dec 2021 --> Apr 2022 | Trial primary completion date: Oct 2021 --> Feb 2022
Clinical • Trial completion date • Trial primary completion date
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over2years
PHASE 3 VERACITY CLINICAL STUDY OF SABIZABULIN IN MEN WITH METASTATIC CASTRATE RESISTANT PROSTATE CANCER WHO HAVE PROGRESSED ON AN ANDROGEN RECEPTOR TARGETING AGENT (SUO 2021)
The Phase 3, VERACITY registration clinical trial is current ongoing in approximately 45 clinical sites with enrollment anticipated to be completed in 2022 and with unblinded results presented in 2023.
Clinical • P3 data
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over2years
Clinical • Trial initiation date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER expression
|
Trodelvy (sacituzumab govitecan-hziy) • sabizabulin (VERU-111)
over2years
Clinical • New P2 trial
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
|
ER positive • HER-2 negative
|
everolimus • fulvestrant • exemestane • sabizabulin (VERU-111)
over2years
To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=41, Active, not recruiting, Veru Inc. | Trial completion date: Sep 2021 --> Dec 2021
Clinical • Trial completion date
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over2years
Clinical • New P2 trial • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
ER expression
|
Trodelvy (sacituzumab govitecan-hziy) • sabizabulin (VERU-111)
over2years
[VIRTUAL] Phase Ib/II study of sabizabulin (VERU-111), an androgen receptor transport disruptor, in men with metastatic castration resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent (ARTA) (ESMO 2021)
In the phase Ib/II clinical trial, oral 63mg daily dosing has a favorable safety profile and chronic dosing is feasible. Efficacy was observed with PSA declines and long term durable responses. The phase III VERACITY study evaluating sabizabulin in chemotherapy naïve men with mCRPC who have failed an AR targeting agent is ongoing.
P1/2 data
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
over2years
Clinical • Enrollment closed
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
almost3years
Clinical • Enrollment open
|
AR (Androgen receptor)
|
enzalutamide capsule • abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide) • sabizabulin (VERU-111)
almost3years
To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=41, Recruiting, Veru Inc. | Trial completion date: Apr 2021 --> Sep 2021 | Trial primary completion date: Mar 2021 --> Aug 2021
Clinical • Trial completion date • Trial primary completion date
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
almost3years
Clinical • New P3 trial
|
AR (Androgen receptor)
|
enzalutamide capsule • abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide) • sabizabulin (VERU-111)
almost3years
The Tubulin Inhibitor VERU-111 in Combination With Vemurafenib Provides an Effective Treatment of Vemurafenib-Resistant A375 Melanoma. (PubMed, Front Pharmacol)
Knockout of Skp2 diminished oncogene AKT expression and contributed to the synergistic inhibitory effect of Vem and VERU-111. Our results indicate a treatment combination of VERU-111 and Vem holds a great promise to overcome Vem-resistance for melanoma patients harboring BRAF (V600E) mutation.
Journal • Combination therapy
|
SKP2 (S-phase kinase-associated protein 2)
|
BRAF V600E • BRAF V600
|
Zelboraf (vemurafenib) • sabizabulin (VERU-111)
3years
To Evaluate Safety and Tolerability of VERU-111 in Men With Advanced Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=41, Recruiting, Veru Inc. | Trial completion date: Jan 2021 --> Apr 2021 | Trial primary completion date: Dec 2020 --> Mar 2021
Clinical • Trial completion date • Trial primary completion date
|
AR (Androgen receptor)
|
sabizabulin (VERU-111)
3years
[VIRTUAL] Clinical study of VERU-111, an oral cytoskeletal disruptor, in metastatic castration-resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent. (ASCO-GU 2021)
8 received prior enzalutamide, 12 abiraterone and 10 both...9/29 (31%) had previously abiraterone, 10/29 (34%)( enzalutmide, 7/29 (24%) both enzalutmide and abiraterone and 4/29 (14%) apalutamide... Based upon this Phase 1b/2 clinical trial, oral VERU-111 has a favorable safety profile allowing for chronic administration and significant and durable antitumor activity. The daily dose of 63mg is being tested in the fully enrolled Phase 2 portion. Oral administration, safe long-term treatment and evidence of antitumor activity highlight a potential prominent role of VERU 111 for the treatment of men with mCRPC who failed an androgen receptor targeting agent.
Clinical
|
AR (Androgen receptor)
|
enzalutamide capsule • abiraterone acetate • Erleada (apalutamide) • sabizabulin (VERU-111)
over3years
Orally available tubulin inhibitor VERU-111 enhances antitumor efficacy in paclitaxel-resistant lung cancer. (PubMed, Cancer Lett)
When tested in a highly paclitaxel-resistant A549/TxR tumor model, VERU-111 is as effective as the parental A549 model in significantly reducing the tumor volume, whereas paclitaxel is essentially ineffective. Collectively, this study showed that VERU-111 is a promising new generation of anti-tubulin agent for the treatment of taxane-resistant lung cancer.
Clinical • Journal • PARP Biomarker
|
CASP3 (Caspase 3)
|
paclitaxel • sabizabulin (VERU-111)
over3years
VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway. (PubMed, Cancer Lett)
Taken together, our results demonstrate the potential anti-cancer efficacy of VERU-111 in in vitro and in vivo. VERU-111 can be explored as a potent therapeutic agent for the treatment of cervical cancer.
Journal • PARP Biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • JAK2 (Janus kinase 2) • BCL2L1 (BCL2-like 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • BIRC5 (Baculoviral IAP repeat containing 5) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CCNB1 (Cyclin B1)
|
BIRC5 expression • BAX expression
|
sabizabulin (VERU-111)