Modulation Of The Tumour Microenvironment Using Either Vascular Disrupting Agents or STAT3 Inhibition in Order to Synergise With PD1 Inhibition in Microsatellite Stable, Refractory Colorectal Cancer

This Phase II research project will test the efficacy, safety, and tolerability of an experimental drug combination: either nivolumab and BBI608 or nivolumab and BNC105 in patients with metastatic colorectal cancer who have previously failed standard of care treatment.

Start Date06 Sep 2018

Sponsor / Collaborator-

NCT03454165 / CompletedPhase 1IIT

A Phase 1 Trial of BNC105P & Ibrutinib in Patients w/ Relapsed/Refractory CLL

A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia(CLL). This study proposes that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. The study will establish the maximum tolerated dose(MTD) of the combination of BNC105P with ibrutinib, characterize the pharmacodynamic effects of BNC105P alone and in combination with ibrutinib in CLL cells, and provide preliminary assessment of the efficacy of the combination in CLL.
The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued

Start Date09 Mar 2018

Sponsor / Collaborator

Dartmouth-Hitchcock Medical Center

NCT01624493 / WithdrawnPhase 1/2

Phase I/II BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients in First or Second Relapse

This phase I/II trial will determine the recommended dose and activity of BNC105P for patients with partially platinum sensitive ovarian cancer in first or second relapse.

Start Date01 Oct 2012

Sponsor / Collaborator

Hoosier Cancer Research Network

[+3]

100 Clinical Results associated with BNC-105P

100 Translational Medicine associated with BNC-105P

100 Patents (Medical) associated with BNC-105P

Literatures (Medical) associated with BNC-105P

01 Nov 2022·EJHaem

A phase I trial of BNC105P and ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia

Article

Author: Pooler, Darcy B. ; Tosteson, Tor D. ; Lansigan, Frederick ; Labrie, Bridget M. ; Lewis, Lionel D. ; Ness, Dylan B. ; Danilov, Alexey V. ; Eastman, Alan

The study rationale was to target CLL cell egress from the stromal niche with ibrutinib and eliminate CLL cells in circulation with BNC105P to potentially obtain deep, long-lasting responses.We therefore conducted an open-label, Phase Ib, dose escalation study of BNC105P and ibrutinib in patients with relapsed/refractory CLL (NCT03454165).Patients were enrolled at the Dartmouth Cancer Center using a Dartmouth College and Dartmouth-Hitchcock Health Institutional Review Board approved protocol and written informed consent.Study patients provided written informed consent prior to the performance of any study procedures and given a copy of the signed written informed consent.

01 Aug 2021·Molecular cancer therapeuticsQ2 · MEDICINE

Gene Expression Signature Correlates with Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Everolimus Alone or with a Vascular Disrupting Agent

Q2 · MEDICINE

Article

Author: Nassar, Amin H. ; Sonpavde, Guru P. ; Pal, Sumanta K. ; Zarei, Mahsa ; Adib, Elio ; Du, Heng ; Jegede, Opeyemi A. ; Alaiwi, Sarah Abou ; Manna, Deborah L. Della ; Braun, David A. ; Naik, Gurudatta ; Yang, Eddy S.

Abstract:

Everolimus monotherapy use for metastatic renal cell carcinoma (mRCC) has diminished due to recent approvals of immune checkpoint and VEGF inhibitors. We hypothesized that gene expression associated with everolimus benefit may provide rationale to select appropriate patients. To address this hypothesis, tumors from a phase I/II trial that compared everolimus alone or with BNC105P, a vascular disrupting agent, were profiled using Nanostring as a discovery cohort. A phase III trial (CheckMate 025) was used for validation. Clinical benefit (CB) was defined as response or stable disease for ≥6 months. A propensity score covariate adjustment was used, and model discrimination performance was assessed using the area under the ROC curve (AUC). In a discovery cohort of 82 patients, 35 (43%) were treated with everolimus alone and 47 (57%) received everolimus + BNC105P. Median PFS (mPFS) was 4.9 (95% CI, 2.8–6.2) months. A four-gene signature (ASXL1, DUSP6, ERCC2, and HSPA6) correlated with CB with everolimus ± BNC105P [AUC, 86.9% (95% CI, 79.2–94.7)]. This was validated in 130 patients from CheckMate 025 treated with everolimus [AUC, 60.2% (95% CI, 49.7–70.7)]. Among 43 patients (52.4%) with low expression of an 18-gene signature, everolimus + BNC105P was associated with significantly longer mPFS compared with everolimus alone (10.4 vs. 6.9 months; HR, 0.49; 95% CI, 0.24–1.002; P = 0.047). These signatures warrant further validation to select patients who may benefit from everolimus alone or with a vascular disrupting agent.

01 Apr 2020·Biochemical and biophysical research communicationsQ3 · BIOLOGY

Unraveling the molecular mechanism of BNC105, a phase II clinical trial vascular disrupting agent, provides insights into drug design

Q3 · BIOLOGY

Article

Author: Wang, Tao ; Wang, Yuxi ; Arnst, Kinsie E ; Wang, Chengdi ; Wu, Chengyong ; Li, Weimin ; Yao, Yijun ; Zhang, Guiping ; Zhang, Zhixiong ; Pu, Dan

Microtubules are made up of tubulin protein and play a very important part in numerous cellular events of eukaryotic cells, which is why they are seen as attractive targets for tumor chemotherapy. BNC105, a known vascular targeting agent, has entered in phase II clinical trials. It has previously been confirmed that BNC105 is an effective microtubule targeting agent for various cancers. BNC105 exhibits selectivity for tumor cells, elicits vascular disrupting effects, and inhibits tumor growth. However, the molecular mechanism of BNC105 is still elusive. Herein, the crystal structure of BNC105 in complex with tubulin protein is revealed, demonstrating the its interaction with the colchicine binding site. In order to thoroughly evaluate its molecular mechanism from a structural-activity-relationship standpoint, the binding mode of tubulin to BNC-105 is compared with colchicine, CA-4 and other BNC-105 derivatives. Our study not only confirms the detailed interactions of the BNC105-tubulin complex, but also offer substantial structural foundation for the design and development of novel benzo[b]furan derivatives as microtubule targeting agents.

News (Medical) associated with BNC-105P

23 Feb 2023

·www.globenewswire.com

Bionomics’ Half-Year Report

ADELAIDE, Australia, Feb. 23, 2023 (GLOBE NEWSWIRE) -- Bionomics Limited (ASX: BNO, NASDAQ: BNOX), today announced its FY2023 report for the half-year ended 31 December 2022. This period represented a transformational time for Bionomics in which the Company made great strides on multiple fronts, including progress on advancing the pipeline, raising capital, and implementing strategic corporate initiatives designed to create long-term shareholder value. The Company recently completed its Phase 2 PREVAIL Study to evaluate BNC210 for the acute treatment of Social Anxiety Disorder (SAD). The PREVAIL Study, initiated in January 2022, was a randomised, double-blind, placebo-controlled, multi-center Phase 2 clinical trial with a single dose treatment conducted at 15 sites in the US and recruited approximately 150 patients with SAD. The PREVAIL Study completed recruitment, and topline data were reported on 19 December 2022. The Company announced that while the primary endpoint, as measured by the change from baseline to the average of the Subjective Units of Distress Scale (SUDS) scores during a 5-minute Public Speaking Challenge was not met in the BNC210-treated patients when compared to placebo, the findings did indicate a consistent trend toward improvements across primary and secondary endpoints and a favourable safety and tolerability profile consistent with previously reported results. The Company is continuing its analysis of the PREVAIL dataset and is assessing the next steps for the development of BNC210 in SAD. The Company continues to progress evaluation of BNC210 in patients with Post-Traumatic Stress Disorder (PTSD) in a randomised, double-blind, placebo-controlled, multi-center Phase 2b clinical trial with a 12-week treatment period recruiting approximately 200 patients. The ATTUNE study has been ongoing in the US, and new sites were recently opened for recruitment in the United Kingdom. The independent Safety Review Committee meets approximately every three months to monitor participant safety and to date, no safety concerns precluding continuation of the trial have been reported; topline results are expected in mid-2023. Bionomics also continued to see progress in its partnership with Merck & Co (known as MSD outside the United States and Canada) to develop α7 receptor positive allosteric modulators (PAMs) targeting cognitive impairment in Alzheimer’s disease with two compounds undergoing Phase 1 safety and biomarker clinical trials. While the internal focus and current research and development spending are restricted to CNS programs, Bionomics continues limited activities to maximise the value of its legacy oncology programs through divestment and/or out-licensing both BNC101 and BNC105. Of the non-core legacy oncology assets, the development program established under the exclusive license agreement of BNC101 to Carina Biotech continued to advance and is projected by Carina to move into the clinic in 1H2023. There is also a Memorandum of Understanding that the Company entered into in February 2021 with EmpathBio for exploring a potential combination of BNC210 and EMP-01 (an MDMA derivative) for the treatment of PTSD. In November 2022, the Company issued 614,026 American Depositary Shares (“ADS”) in the United States at a price of US$7.80 per ADS, raising gross proceeds of US$5,000,000 ($7,419,235). The offering price of US$7.80 per ADS ($0.0641 per ordinary share) represented a 1.63% discount to the 15-day volume weighted average price. Each ADS represents 180 fully paid Bionomics' ordinary shares and resulted in 115,384,680 fully paid shares being issued. The net proceeds raised were $5,806,168. In December 2022, the Company announced a critical milestone for the leadership team with the appointment of Dr. Spyridon "Spyros" Papapetropoulos starting in January 2023 as Bionomics' President, Chief Executive Officer, and Director. In conjunction with this development, it was announced that Dr. Errol De Souza, who had been serving as Bionomics' Executive Chairman since November 2018, would be stepping back from the role and, in 1 January 2023 resumed the role of Non-Executive Chairman of the Board of Directors. The Company's cash balance as of 31 December 2022 was $30,698,362 (30 June 2022: $35,564,857). FOR FURTHER INFORMATION, PLEASE CONTACT: Bionomics Limited Bionomics Limited Adrian Hinton Ms Suzanne Irwin Acting Chief Financial Officer Company Secretary +61 8 8150 7400 +61 8 8150 7400 ahinton@bionomics.com.au CoSec@bionomics.com.au About Bionomics Limited Bionomics (ASX:BNO, NASDAQ:BNOX) is a clinical-stage biopharmaceutical company developing novel, allosteric ion channel modulators designed to transform the lives of patients suffering from serious central nervous system (CNS) disorders with high unmet medical need. Bionomics is advancing its lead drug candidate, BNC210, an oral, proprietary, selective negative allosteric modulator of the α7 nicotinic acetylcholine receptor, for the acute treatment of Social Anxiety Disorder (SAD) and chronic treatment of Post-Traumatic Stress Disorder (PTSD). Beyond BNC210, Bionomics has a strategic partnership with Merck & Co, Inc (known as MSD outside the United States and Canada) with two drugs in early-stage clinical trials for the treatment of cognitive deficits in Alzheimer’s disease and other central nervous system conditions. www.bionomics.com.au Factors Affecting Future Performance This announcement contains “forward-looking” statements within the meaning of the U.S. federal securities laws. Any statements contained in this announcement that relate to prospective events or developments, including, without limitation, statements related to the Offering are deemed to be forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “projects,” “forecasts,” “will” and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by these forward-looking statements. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Actual results could differ materially from those discussed in this ASX announcement.

Phase 2License out/inExecutive ChangePhase 1

23 Feb 2023

·www.biospace.com

Bionomics’ Half-Year Report - February 23, 2023

ADELAIDE, Australia, Feb. 23, 2023 (GLOBE NEWSWIRE) -- Bionomics Limited (ASX: BNO, NASDAQ: BNOX), today announced its FY2023 report for the half-year ended 31 December 2022. This period represented a transformational time for Bionomics in which the Company made great strides on multiple fronts, including progress on advancing the pipeline, raising capital, and implementing strategic corporate initiatives designed to create long-term shareholder value. The Company recently completed its Phase 2 PREVAIL Study to evaluate BNC210 for the acute treatment of Social Anxiety Disorder (SAD). The PREVAIL Study, initiated in January 2022, was a randomised, double-blind, placebo-controlled, multi-center Phase 2 clinical trial with a single dose treatment conducted at 15 sites in the US and recruited approximately 150 patients with SAD. The PREVAIL Study completed recruitment, and topline data were reported on 19 December 2022. The Company announced that while the primary endpoint, as measured by the change from baseline to the average of the Subjective Units of Distress Scale (SUDS) scores during a 5-minute Public Speaking Challenge was not met in the BNC210-treated patients when compared to placebo, the findings did indicate a consistent trend toward improvements across primary and secondary endpoints and a favourable safety and tolerability pro with previously reported results. The Company is continuing its analysis of the PREVAIL dataset and is assessing the next steps for the development of BNC210 in SAD. The Company continues to progress evaluation of BNC210 in patients with Post-Traumatic Stress Disorder (PTSD) in a randomised, double-blind, placebo-controlled, multi-center Phase 2b clinical trial with a 12-week treatment period recruiting approximately 200 patients. The ATTUNE study has been ongoing in the US, and new sites were recently opened for recruitment in the United Kingdom. The independent Safety Review Committee meets approximately every three months to monitor participant safety and to date, no safety concerns precluding continuation of the trial have been reported; topline results are expected in mid-2023. Bionomics also continued to see progress in its partnership with Merck & Co (known as MSD outside the United States and Canada) to develop α7 receptor positive allosteric modulators (PAMs) targeting cognitive impairment in Alzheimer’s disease with two compounds undergoing Phase 1 safety and biomarker clinical trials. While the internal focus and current research and development spending are restricted to CNS programs, Bionomics continues limited activities to maximise the value of its legacy oncology programs through divestment and/or out-licensing both BNC101 and BNC105. Of the non-core legacy oncology assets, the development program established under the exclusive license agreement of BNC101 to Carina Biotech continued to advance and is projected by Carina to move into the clinic in 1H2023. There is also a Memorandum of Understanding that the Company entered into in February 2021 with EmpathBio for exploring a potential combination of BNC210 and EMP-01 (an MDMA derivative) for the treatment of PTSD. In November 2022, the Company issued 614,026 American Depositary Shares (“ADS”) in the United States at a price of US$7.80 per ADS, raising gross proceeds of US$5,000,000 ($7,419,235). The offering price of US$7.80 per ADS ($0.0641 per ordinary share) represented a 1.63% discount to the 15-day volume weighted average price. Each ADS represents 180 fully paid Bionomics' ordinary shares and resulted in 115,384,680 fully paid shares being issued. The net proceeds raised were $5,806,168. In December 2022, the Company announced a critical milestone for the leadership team with the appointment of Dr. Spyridon "Spyros" Papapetropoulos starting in January 2023 as Bionomics' President, Chief Executive Officer, and Director. In conjunction with this development, it was announced that Dr. Errol De Souza, who had been serving as Bionomics' Executive Chairman since November 2018, would be stepping back from the role and, in 1 January 2023 resumed the role of Non-Executive Chairman of the Board of Directors. The Company's cash balance as of 31 December 2022 was $30,698,362 (30 June 2022: $35,564,857). FOR FURTHER INFORMATION, PLEASE CONTACT: Bionomics Limited Bionomics Limited Adrian Hinton Ms Suzanne Irwin Acting Chief Financial Officer Company Secretary +61 8 8150 7400 +61 8 8150 7400 ahinton@bionomics.com.au CoSec@bionomics.com.au About Bionomics Limited Bionomics (ASX:BNO, NASDAQ:BNOX) is a clinical-stage biopharmaceutical company developing novel, allosteric ion channel modulators designed to transform the lives of patients suffering from serious central nervous system (CNS) disorders with high unmet medical need. Bionomics is advancing its lead drug candidate, BNC210, an oral, proprietary, selective negative allosteric modulator of the α7 nicotinic acetylcholine receptor, for the acute treatment of Social Anxiety Disorder (SAD) and chronic treatment of Post-Traumatic Stress Disorder (PTSD). Beyond BNC210, Bionomics has a strategic partnership with Merck & Co, Inc (known as MSD outside the United States and Canada) with two drugs in early-stage clinical trials for the treatment of cognitive deficits in Alzheimer’s disease and other central nervous system conditions. Factors Affecting Future Performance This announcement contains “forward-looking” statements within the meaning of the U.S. federal securities laws. Any statements contained in this announcement that relate to prospective events or developments, including, without limitation, statements related to the Offering are deemed to be forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “projects,” “forecasts,” “will” and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by these forward-looking statements. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Actual results could differ materially from those discussed in this ASX announcement.

Phase 2Phase 1License out/inExecutive Change

100 Deals associated with BNC-105P

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ovarian Cancer	Phase 2	US	Bionomics Ltd.	13 May 2012
Mesothelioma	Phase 2	AU	Bionomics Ltd.	26 Mar 2010
Metastatic Clear Cell Renal Cell Carcinoma	Phase 2	US	Bionomics Ltd.	01 Jan 2010
Metastatic Clear Cell Renal Cell Carcinoma	Phase 2	AU	Bionomics Ltd.	01 Jan 2010
Metastatic Clear Cell Renal Cell Carcinoma	Phase 2	SG	Bionomics Ltd.	01 Jan 2010
Renal Cell Carcinoma	Phase 2	US	Bionomics Ltd.	04 Jul 2009
Chronic Lymphocytic Leukemia	Preclinical	AU	Bionomics Ltd.	-
Colorectal Cancer	Preclinical	AU	Bionomics Ltd.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01624493 (ANZGOG-1103, Pubmed) Manual	Phase 1	Platinum-Sensitive Ovarian Carcinoma	15	carboplatin+gemcitabine+BNC105P	whypfwcoxh(kbqtrwfyyq) = aqcwhpfaju qzrtmhmjon (memjgwkcpo ) View more	Positive	01 Jan 2019
NCT01624493 (ANZGOG-1103, Pubmed) Manual	Phase 1	Platinum-Sensitive Ovarian Carcinoma	15	carboplatin+gemcitabine	-	Positive	01 Jan 2019
AACR2018	Phase 2	Acute Myeloid Leukemia	-	BNC105	sayyhgiluw(gojqypywmk) = anrzipimtg zayclgkrhs (rgyfvjdsqk )	-	01 Jul 2018
NCT01624493 (ANZGOG and HOG, ASCO2013)	Phase 1/2	Platinum-Sensitive Ovarian Carcinoma	110	BNC105P + gemcitabine-carboplatingemcitabine-carboplatin	kwktscskqn(wlivjhipwx) = mvjcttywse agzrfeblok (dsbydhbiqm ) View more	-	20 May 2013
NCT01624493 (ANZGOG and HOG, ASCO2013)	Phase 1/2	Platinum-Sensitive Ovarian Carcinoma	110	gemcitabine-carboplatingemcitabine-carboplatin	cekqquyqhn(ymtdvfdrxh) = mlhpnjfgyg nmowkrrkhj (pndsscgwuo )	-	20 May 2013
ASCO2012	Phase 2	Malignant Pleural Mesothelioma Second line	30	BNC105P	xibifybugg(clwjikjrlm) = osecjovikj tcrnmoioal (cpfthkvvsx ) View more	Negative	20 May 2012
AACR2012	Phase 1/2	Platinum-Resistant Ovarian Carcinoma	-	BNC105P	gszpxgzbho(masciklkyy) = qhvpbvnnmp bjmaynezcg (hkzvzidkgl )	-	15 Apr 2012
AACR2012	Phase 1/2	Platinum-Resistant Ovarian Carcinoma	-	Cisplatin	gszpxgzbho(masciklkyy) = cmzcjwkoua bjmaynezcg (hkzvzidkgl )	-	15 Apr 2012
ASCO_GU2012	Phase 1/2	Metastatic Renal Cell Carcinoma	-	BNC105P	xqkjvwchfh(yeojnpyjtb) = zioxjrixro rlivxkkqbe (fxwrsysvmg )	-	10 Feb 2012

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