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GNS Healthcare Chosen to Present Discovery of New Clinical Predictors of Overall Survival in Metastatic Colorectal Cancer at ESMO 2019 in Collaboration with the Alliance for Clinical Trials in Oncology

On July 2, 2019 GNS Healthcare (GNS), a leading precision medicine company, together with the Alliance for Clinical Trials in Oncology (Alliance), is reported discoveries of predictive biomarkers for metastatic colorectal cancer (mCRC) patient response to receiving different treatments of cetuximab, bevacizumab, and panitumumab this week at the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer 2019 conference held in Barcelona, Spain (Press release, GNS Healthcare, JUL 2, 2019, View Source [SID1234537371]). Patient subpopulation-specific prognostic factors of overall survival (OS) were also discovered. The in silico patient models identified AST level, primary side of tumor, intra-abdominal metastasis status as ubiquitous predictors of OS. KRAS status and hemoglobin levels were found to be predictors specific to the side of tumor location.

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The study titled "Bayesian machine learning on CALGB/SWOG 80405 (Alliance) and PEAK data identifies heterogeneous landscape of clinical predictors of overall survival (OS) in different populations of metastatic colorectal cancer (mCRC)" was selected to be presented in a poster discussion session, Friday July 5 from 10 am–5:15 pm local time.

Identification of prognostic factors of OS for subpopulations of patients with colorectal cancer is the key to better risk stratification at treatment initiation and identifying predictive factors for treatment response is crucial for making personalized treatment decisions.

In this study, one of several conducted by GNS and the Alliance, Bayesian machine learning approach was applied to the CALGB/SWOG 80405 (Alliance) and PEAK clinical trials datasets to discover gender and primary side specific predictors of OS in mCRC and patient subpopulations with better response to a given treatment.

Using clinical data from more than 2,000 patients with mCRC and GNS’ powerful causal AI platform, Reverse Engineering & Forward Simulation (REFS), nine independent predictive model ensembles were built to understand predictive biomarkers for patient response to receiving different treatments (cetuximab, bevacizumab, or panitumumab) and to identify patient subpopulation-specific prognostic factors of OS.

The study also identified gender-specific predictors, specifically creatinine level, intra-abdominal metastasis status, and the interaction of albumin and neutrophil levels. Urine protein levels were shown to be predictive of better efficacy from cetuximab treatment in patients with mCRC and left-sided tumors.

"We have never been in a better position to unravel drivers of disease and patient response to specific drugs. We built an in silico patient model of colorectal cancer and were able to uncover biomarkers that tell us which patients will respond to which treatment, and most importantly, why. This is what will get us to the point of delivering personalized medicine and eradicating disease," said Colin Hill, GNS Chairman, CEO, and Co-Founder.

"There is no such thing as a one-size-fits-all approach," said Alan P. Venook, MD, Study Chair for the CALGB/SWOG 80405 (Alliance) study, Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California-San Francisco, and Shorenstein Associate Director for Program Development at the Helen Diller Family Comprehensive Cancer Center. "The better we understand how this disease progresses and which biomarkers predict treatment response, the closer we will get to curing it. We are committed to leveraging the best tools at hand – GNS’ powerful AI, comprehensive data, and the best minds in research – to cure cancer."

Previous results from these collaborations were presented in June 2018 at the ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois and at ESMO (Free ESMO Whitepaper) 2018 in Munich, Germany.

As one of the most common cancers in the U.S., there are an estimated 140,000 new cases of colorectal cancer diagnosed each year. There is still much to learn about the factors that drive progression and for patients with mCRC, the optimal treatment is still unknown.

About the Alliance for Clinical Trials in Oncology
The Alliance for Clinical Trials in Oncology develops and conducts clinical trials with promising new cancer therapies, and utilizes the best science to develop optimal treatment and prevention strategies for cancer, as well as research methods to alleviate side effects of cancer and cancer treatments. The Alliance is part of the National Clinical Trials Network (NCTN) sponsored by the National Cancer Institute (NCI) and serves as a research base for the NCI Community Research Oncology Program (NCORP).
To learn more about the Alliance, visit www.AllianceforClinicalTrialsinOncology.org.

Apexian Pharmaceuticals’ Clinical Candidate, APX3330, to Be Studied in Diabetic Models of Preleukemic Cells With Specific Mutations to Leukemia

On July 2, 2019 Apexan Pharmaceuticals, Inc. is reported that The National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health has awarded a $2.3 million grant to Dr. Reuben Kapur and Dr. Mark R. Kelley, investigators in the Wells Center for Pediatric Research at the IU School of Medicine, to conduct studies that focus on preleukemic stem cells bearing specific mutations and their progression to full-blown cancer in the context of diabetes (Press release, Apexian Pharmaceuticals, JUL 2, 2019, View Source [SID1234537370]). The funds will also be used to examine and assess cancer progression in animal models under conditions of hyperglycemia, or high blood sugar, over the next four years. In these studies, they will build on their recently published work in Cell Stem Cell, demonstrating that APX3330 blocks this progression under conditions of inflammation.

APX3330 is a lead compound of Apexian Pharmaceuticals, Inc., a clinical stage drug development company focused on advancing APX3330 for the treatment of diseases mediated by the APE1/Ref-1 protein. Dr. Kelley is the Chief Scientific Officer of Apexian.

Results of Apexian’s recently completed Phase I clinical trial of APX3330 in patients with advanced, end-stage solid tumors were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). The study confirmed the safety profile of APX3330 when given chronically as an orally-administered pill and identified a recommended phase II dose for further clinical development of APX3330 in a variety of possible indications.

Tumor biopsy data from the study confirmed the mechanism of action of APX3330 interacting with its molecular target, the APE1/Ref-1 protein, a gatekeeper for transcription factor activity. According to Dr. Kelley, "Given the importance of the APE1/Ref-1 protein in a variety of disease processes, including cancer, diabetic macular edema (DME) and inflammatory bowel disease (ulcerative colitis) and others, the phase I results confirm APX3330’s ability to control the drug target in humans. The NHLBI grant will be used to increase our understanding of the links between diabetes and cancer, allowing us to explore the potential of APX3330 in these areas of high unmet medical need."

A2A Pharmaceuticals Appoints Dr. Sotirios Stergiopoulos Chief Executive Officer

On July 2, 2019 A2A Pharmaceuticals Inc. (A2A), a biotechnology company committed to the advancement of innovative scientific research and new therapeutic agents, reported the appointment of Dr. Sotirios G. Stergiopoulos as President and Chief Executive Officer (Press release, A2A Pharmaceuticals, JUL 2, 2019, View Source [SID1234537369]). He has held the position as Founder and Chairman of the Board since 2016. Sotirios will maintain a seat on the Board of Directors.

Dr. Stergiopoulos joins A2A from Ipsen where he served as the Chief Medical Officer, SVP and Head of Global Medical Affairs since January 2017. In this role, he was responsible for the overall medical and clinical governance of the company, as well as the creation of a global medical affairs organization. Dr. Stergiopoulos played a key role in Ipsen’s oncology TA strategy. Sotirios held numerous leadership positions in the pharmaceutical industry with companies including Novartis, Bayer, and Celgene.

Dr. Stergiopoulos is a physician executive with a B.S. from Stony Brook University, an M.D. from Poznan University of Medical Sciences, and an M.B.E.E. from the Johns Hopkins University. He has trained at the National Institutes of Health, the Albert Einstein College of Medicine, and Harvard University.

Edward Painter, who has served as CEO of A2A since 2016, will take the role of Chief Investment Officer and Chairman of the Board. Edward will work with Sotirios to optimize the allocation of capital across A2A’s programs and build the management team.

Mr. Painter remarked, "I am delighted to have succeeded in recruiting Sotirios to the CEO role at A2A. His leadership in the pharmaceutical industry, as well as experience in clinical medicine and Oncology drug development, will be critical to A2A’s advancement of therapeutics for Oncology and other life-threatening diseases into the clinic for the patients that need them."

Dr. Stergiopoulos explained, "A2A’s novel approach to drug development has the potential to bring true best in class therapies to patients suffering with cancer and other difficult to treat diseases. I am encouraged by the platform utilized by A2A to pursue difficult targets and look forward to working alongside Edward and the team at A2A to translate the technology into therapies for patients."

Novocure to Report Second Quarter 2019 Financial Results

On July 2, 2019 Novocure (NASDAQ: NVCR) reported that it will report financial results for the second quarter 2019 on Thursday, July 25, 2019, before the U.S. financial markets open (Press release, NovoCure, JUL 2, 2019, View Source [SID1234537367]). Novocure management will host a conference call and webcast to discuss its financial results for the three months ended June 30, 2019, at 8 a.m. EDT on Thursday, July 25, 2019.

Novocure to report second quarter 2019 financial results

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Analysts and investors can participate in the conference call by dialing 855-442-6895 for domestic callers and 509-960-9037 for international callers, using the conference ID 1438824. The webcast and earnings slides presented during the webcast can be accessed live from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for replay for at least 14 days following the call.

TRACON Pharmaceuticals Provides Update On Phase 1/2 Trial Of TRC253 In Patients With Metastatic Castrate Resistant Prostate Cancer

On July 2, 2019 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration through our license to Santen Pharmaceutical Co. Ltd., and utilizing our product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported an update on its TRC253 program for the treatment of metastatic castrate resistant prostate cancer, which was licensed from Janssen Pharmaceutica N.V. in 2016 (Press release, Tracon Pharmaceuticals, JUL 2, 2019, View Source [SID1234537366]).

Phase 1 data from the ongoing Phase 1/2 clinical trial published in the 2019 ASCO (Free ASCO Whitepaper) Proceedings

21 patients with metastatic castrate resistant prostate cancer who had progressed on prior Xtandi (enzalutamide) or Erleada (apalutamide) treatment were enrolled into one of six cohorts of escalating doses of TRC253.

Target PK exposures were achieved consistently with the 280 mg daily oral dose, which was selected as the recommended Phase 2 dose.

The single patient with a F877L androgen receptor (AR) point mutation at baseline remained on treatment for 49 weeks with a partial response by RECIST.

The remaining 20 patients did not have a F877L AR point mutation at baseline, and 48% (10) remained on study for at least 6 months and one patient had a greater than 50% decrease in prostate specific antigen (PSA).

TRC253 was well-tolerated and no drug-related serious adverse events were reported. Drug-related adverse events included QTcF prolongation, elevated lipase, fatigue, arthralgia, diarrhea, and platelet count decrease.

Additional data are available on the ASCO (Free ASCO Whitepaper) website: View Source
Phase 2 portion of the ongoing Phase 1/2 trial amended to add an additional cohort of patients

Based on evidence of potential efficacy in the data from the completed Phase 1 portion of the study, an additional cohort of patients was added to the ongoing Phase 2 study. This cohort will test the hypothesis of whether TRC253 has efficacy in mCRPC patients with a defined point mutation other than F877L AR.

Enrollment is ongoing in the new cohort with a defined point mutation, as well as the two existing cohorts, the first including patients with a F877L AR mutation and the second consisting of patients with another basis for resistance to Xtandi or Erleada.
"We are pleased to have successfully completed the Phase 1 portion of the first-in-human study of TRC253 and look forward to the availability of Phase 2 data, which we expect in the second half of 2020," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "Following delivery of the Phase 2 data, Janssen will have the right to reacquire the TRC253 program in return for an opt-in fee of $45 million and further success-based milestone and royalty payments."

About TRC253 (formerly JNJ-63576253)

TRC253 is a novel, orally bioavailable small molecule discovered and developed by Janssen that is a potent, high affinity competitive inhibitor of the AR. TRC253 is also a pan-inhibitor of multiple AR mutations, including the F877L mutation, and is under development for the treatment of men with prostate cancer in a Phase 1/2 clinical trial (NCT02987829). The AR F877L mutation results in an alteration in the ligand binding domain that confers resistance to current AR inhibitors.

Activation of the AR is crucial for the growth of prostate cancer at all stages of the disease. Therapies targeting the AR have demonstrated clinical efficacy by extending time to disease progression, and in some cases, the survival of patients with metastatic castration-resistant prostate cancer. However, resistance to these agents is often observed and several molecular mechanisms of resistance have been identified, including amplification, overexpression or mutation of the AR.

TRC253 is intended to address resistance mechanisms to current AR inhibitors by specifically targeting mutations in the AR ligand binding domain. TRC253 also potently inhibits signalling through the wild type AR. These susceptible AR mutations have been identified using circulating tumor DNA assays, potentially allowing for selected patient biomarker-directed therapy.

Following completion of the initial Phase 1/2 clinical trial, Janssen will have an exclusive option to reacquire full rights to TRC253 for an upfront payment of $45 million to TRACON, and obligations to pay regulatory and commercialization milestones totaling up to $137.5 million upon achievement of specified events and a low single-digit royalty. If Janssen does not exercise its exclusive option to reacquire the program, TRACON would then retain worldwide development and commercialization rights to the program and would be obligated to pay Janssen a total of up to $45 million in development and regulatory milestones upon achievement of specified events, in addition to a low single digit royalty.