On December 4, 2019 BIOASIS TECHNOLOGIES INC. (OTCQB:BIOAF; TSX.V:BTI), ), a pre-clinical, research-stage biopharmaceutical company developing its proprietary xB3 platform technology for the delivery of therapeutics across the blood-brain barrier (the "BBB") and the treatment of central nervous system ("CNS") disorders in areas of high unmet medical need, including brain cancers and neurodegenerative diseases, reported the creation of the Medical Oncology Advisory Board and the appointments of Dr. John DeGroot M.D., Dr. Hope Rugo M.D. and Dr. Javier Cortés M.D. PhD (Press release, biOasis, DEC 4, 2019, View Source [SID1234551934]). The goals of this board will be to guide the clinical strategy and design of the xB3-001 clinical program for the treatment of HER2+ breast cancer and brain metastases. The Medical Oncology Advisory Board will be chaired by José Iglesias, MD, who has been appointed consultant Chief Medical Officer for Bioasis Technologies Inc.

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Dr. José Iglesias, Chairperson of the Advisory Board in his role of consultant Chief Medical Officer is a biopharmaceutical industry veteran with 30 years of executive experience in all phases of oncology clinical drug development covering the areas of solid tumor oncology, immuno-oncology and translational medicine. His career includes senior positions at Eli Lilly, Amgen, Abraxis Bioscience, Celgene, Bionomics, Biothera, Apobiologix and Boston Biomedical. Dr. Iglesias is author or co-author of more than 60 peer-reviewed publications with over 6,000 literature citations and an active member of ASCO (Free ASCO Whitepaper), ESMO (Free ESMO Whitepaper) and AACR (Free AACR Whitepaper). He graduated from the University of Montevideo, Uruguay, and received additional training at the Weizmann Institute of Science (Rehovot, Israel), Duke University Medical Center (Durham, NC) and the University of Toronto.

"I am delighted to welcome José to the Bioasis team, strengthening our oncology development expertise at a critical time as we progress our lead program xB3-001 for the treatment of HER2+ breast cancer and brain metastases. I am also extremely pleased to welcome John, Hope and Javier to the Medical Oncology Advisory Board. Each member is a leader in their field with proven track records of excellence in clinical practice and clinical drug development in the areas of breast cancer and CNS oncology." Deborah Rathjen added, Ph.D., Executive Chair of Bioasis. "We look forward to continuing to benefit from the strength of the collective experience of our medical board as we advance our xB3 programs toward the clinic."

Dr. José Iglesias commented, "Treatment of HER2+ breast cancer that has metastasized to the brain remains a significant challenge. To date, xB³-001 has demonstrated highly encouraging preclinical results, and I am excited to be working with Dr. Rathjen and the Bioasis team to continue to advance this class-leading technology."

Dr. John de Groot is a Professor, and Chairman ad interim, in the Department of Neuro-Oncology at The University of Texas MD Anderson Cancer Center. He is an expert in the fields of glioma angiogenesis and molecularly targeted therapy. Dr. de Groot has served as the principal investigator (PI) or co-investigator on multiple funded National Cancer Institute, foundation, and industry-sponsored grants. He is the principal investigator of numerous clinical trials involving novel agents being tested in patients with glioblastoma and is a leader of MD Anderson’s Glioblastoma Moon Shot. Dr. de Groot has over 112 peer reviewed articles. He is or has been a peer reviewer for 23 scientific journals, both national & international, and is on four editorial review boards. He completed his medical education at The University of Texas Medical Branch at Galveston, and pursued internship and residency at The Johns Hopkins School of Medicine.

Dr. Hope S. Rugo is Professor of Medicine at the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, where she is also the director of Breast Oncology and Clinical Trials Education. She is a principal investigator of multiple clinical trials focusing on combining novel targeted therapeutics with standard treatment to improve the treatment of both early and late stage breast cancer and improving safety with targeted agents and has published widely in this area with over 200 peer reviewed articles. Dr. Rugo is an active member of the Translational Breast Cancer Research Consortium (TBCRC), a principal investigator of several TBCRC trials and is the co-chair of the Triple Negative Working Group. She is a member of the Breast Committee for the Alliance cooperative group, and is an associate editor for the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting educational book. Dr. Rugo graduated from the University of Pennsylvania School of Medicine. She completed a residency in internal medicine followed by a fellowship in hematology and oncology at UCSF as well as a research fellowship at Stanford University.

From June 2003 to July 2015, Dr.Cortés worked in the Department of Medical Oncology at the Hospital Vall d’Hebron, Barcelona, where he has been Coordinator of the Teaching and Training Programme for Residents in Oncology and Senior Specialist in the Area of Breast Cancer with a special interest in new drug development. Dr. Cortés was the Head of the Breast Cancer Program and the Melanoma Unit from July 2006 to August 2015. From September 2015 to October 2018, he has been Head of the Breast Cancer and Gynecological tumors at Ramon y Cajal University Hospital in Madrid. He is Clinical Investigator of the Breast Cancer Research Program at Vall d’Hebron Institute of Oncology, and Head of Breast Cancer Program, IOB Institute of Oncology, Madrid and Barcelona, Spain. Dr Cortés is the author of more than 240 publications, with a focus on breast tumors and new drugs, and more than 500 communications at multiple conferences. He actively participates in the development of numerous national and international clinical investigations. Dr Cortés received a degree in Medicine and Surgery from the Universidad Autónoma de Madrid with continued studies at the University of Navarra, specializing in Medical Oncology at the Clínica Universitaria de Navarra. In addition to his medical specialties, he has two masters’ degree in Medical Direction and Clinical Management from the Universidad Nacional de Educación a Distancia (UNED) and Research Methodology in Health Sciences from the Universidad Autónoma de Barcelona as well as a degree in Statistics in Health Sciences from the same university.

On December 4, 2019 ImmunityBio, a privately held immunotherapy company, reported that it has received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for its interleukin-15 (IL-15) agonist complex, N-803, in combination with Bacillus Calmette-Guerin (BCG), for the treatment of patients with BCG-unresponsive non-muscle invasive bladder carcinoma in situ (CIS) (Press release, ImmunityBio, DEC 4, 2019, View Source [SID1234551933]).

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This grant of Breakthrough Designation follows on the receipt of Fast Track Designation from the U.S. Food and Drug Administration for N-803 in 2017. The FDA’s Breakthrough Therapy Designation program is designed to expedite the development and review of drugs intended to treat serious conditions and fill unmet medical needs.1 The FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.

"We are pleased that the FDA has granted Breakthrough Therapy Designation to N-803 in combination with BCG for the treatment of patients with Non-Muscle Invasive Bladder Cancer with CIS," said Dr. Patrick Soon-Shiong, Chairman and CEO of ImmunityBio. "We look forward to accelerating our work on N-803 to bring greater hope to the thousands of people living with the serious consequences of bladder cancer and to address the unmet need to avoid surgical removal of the bladder in these high-risk patients. Patients who fail current standard of care and who have high risk carcinoma in situ of the bladder are left with a difficult choice of having their bladder removed, a procedure fraught with a clinically significant mortality and morbidity rates. The potential opportunity to avoid this procedure and change the course of this disease with the addition of N-803 is immensely gratifying," he said.

"The favorable safety profile and initial efficacy results from our phase 1 study strongly suggest we may be able to improve the treatment for a disease that has not had non-surgical treatment options for over 30 years," said ImmunityBio Chief Medical Officer, Dr. John Lee.

ImmunityBio’s N-803, an IL-15 Superagonist

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

N-803 is currently being evaluated for adult patients in two clinical NMIBC trials. QUILT 2.005 is investigating use of N-803 in combination with BCG for patients with BCG-naïve NMIBC; QUILT 3.032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC.

The Urgent, Unmet Need to Treat NMIBC and Avoid Cystectomy

Bladder cancer has a high incidence worldwide, with 199,922 deaths and an estimated 549,393 new cases in 2018.2 In the United States, bladder cancer is the fourth most commonly diagnosed solid malignancy in men and the twelfth for women; The American Cancer Society estimates 80,470 new cases and 17,670 deaths in 2019.3 Bladder cancers are described based on how far they have invaded into the wall of the bladder. NMIBC occurs when the cancer has not grown into the main muscle layer of the bladder. Approximately 75-85% of all newly diagnosed cases of bladder cancer are non-muscle invasive bladder cancer (NMIBC).4

For the last 30 years, BCG immunotherapy has been the standard for treating NMIBC. However, disease recurrence and progression rates remain unacceptably high. Standard of care recommendations for these patients include lifetime invasive surveillance and rapid treatment of recurrences, creating a substantial financial burden and drastic impact on quality of life. Of those patients who experience recurrence, approximately 30% will progress and succumb to their disease over a 15-year period, and another 50% will undergo radical cystectomy of the bladder in an attempt to control their disease.5

For high-risk NMIBC patients who are BCG-unresponsive with persistent or recurrent disease, treatment guidelines recommend a surgical procedure called radical cystectomy, a surgery to remove the entire bladder that may require removal of other surrounding organs. In men, removal of the prostate may be necessary, and in women, surgeons may also remove the uterus, fallopian tubes, ovaries and cervix, and occasionally a portion of the vagina. Despite the advent of minimally invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in patients who undergo cystectomy remain unacceptably high at 5.1-8.1% and 28-64%, respectively.6 Based on this urgent need, FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.

On December 4, 2019 Personal Genome Diagnostics Inc. (PGDx), a leader in cancer genomics, reported that it received Investigational Device Exemption (IDE) approval from the U.S. Food and Drug Administration (FDA) for the use of the company’s elio tissue complete assay in a Merck trial of pembrolizumab-based combination therapy (Press release, Personal Genome Diagnostics, DEC 4, 2019, View Source [SID1234551931]). The PGDx elio assay will be used during the trial to analyze genomic markers to direct patient enrollment and stratification.

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"We’re pleased with the FDA’s decision to approve PGDx’s elio tissue complete assay for this trial, as it validates the robustness of the test and reinforces the role of diagnostic biomarkers in investigating treatment strategies for patients living with cancer," said Doug Ward, Chief Executive Officer at PGDx. "Further, Merck’s selection of this assay for use in their trials underscores its value and performance in ongoing oncology research."

The PGDx elio tissue complete panel is a 500+ gene test for somatic alterations that detects single nucleotide variants (SNVs), small insertion/deletions, amplifications, rearrangements, microsatellite instability (MSI) and tumor mutation burden. PGDx provides genomic solutions from biomarker discovery to companion diagnostic development through its CAP/CLIA certified laboratory and is developing a portfolio of regulated tissue-based and liquid biopsy genomic products to enable local next-generation sequencing (NGS) testing in laboratories worldwide.

On December 4, 2019 Foundation Medicine, Inc. reported it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneCDx to be used as a companion diagnostic for Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen (Press release, Foundation Medicine, DEC 4, 2019, View Source [SID1234551930]). FoundationOne CDx is the first and only FDA-approved broad comprehensive genomic profiling (CGP) test for all solid tumors, including breast cancer, that incorporates multiple companion diagnostics.

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"Foundation Medicine is proud to achieve another FDA approval for FoundationOne CDx as a companion diagnostic for Piqray for the treatment of metastatic breast cancer with a PIK3CA mutation," stated Brian Alexander, M.D., M.P.H. Foundation Medicine’s Chief Medical Officer. "The advancements we are seeing in the treatment of breast cancer underscore the importance of harnessing genomic insights to enable personalized medicine. Taking a comprehensive and validated approach to genomic testing is critical for patients with metastatic breast cancer to help physicians determine a treatment roadmap upfront that may include FDA-approved targeted therapies like Piqray."

In May of 2019, Novartis announced that the FDA approved Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen metastatic breast cancer with a PIK3CA mutation following progression on or after an endocrine-based regimen. PIK3CA is the most commonly mutated gene in HR+/HER2- breast cancer; approximately 40% of patients living with HR+/HER2- breast cancer have this mutation1. Professional guidelines were updated in September of 2019 to recommend assessment for PIK3CA mutations as part of the workup of HR+/HER2- advanced or metastatic breast cancer.

Piqray is the first and only treatment specifically for patients with a PIK3CA mutation in HR+/HER2- advanced breast cancer. Foundation Medicine and Novartis have an ongoing collaboration to support the development of companion diagnostics for the Novartis oncology portfolio.

Foundation Medicine will also be presenting new data at this year’s San Antonio Breast Cancer Symposium (SABCS) highlighting the utility of comprehensive genomic profiling in cancer care, including research on PIK3CA, as well as emerging biomarkers in breast cancer.

On December 4, 2019 AVEO Oncology (NASDAQ: AVEO) reported that previously reported data from its Phase 3 TIVO-3 study were published in The Lancet Oncology (Press release, AVEO, DEC 4, 2019, View Source [SID1234551929]). TIVO-3 is the Company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA), the Company’s vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), to sorafenib in 350 subjects with highly refractory metastatic renal cell carcinoma (RCC). The article, titled "Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study", is available online first via this link.

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"TIVO-3 represents the first study to demonstrate a superior progression free survival (PFS) benefit versus an active comparator in patients with advanced or metastatic RCC who have failed at least two prior lines of therapy, including a VEGFR-TKI, and the first Phase 3 study to investigate a predefined subpopulation of patients who received prior immunotherapy, the emerging standard of care for earlier lines of therapy," said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center, principal investigator of the TIVO-3 trial, and lead author of the publication. "Data from this study reinforce that tivozanib has the potential to serve as an effective, tolerable therapy in the evolving RCC treatment landscape."

"With durable improvements observed in this highly refractory RCC patient population, TIVO-3 offers valuable insight into the potential sequencing of therapy following earlier TKI and immunotherapy treatment," said Michael Bailey, president and chief executive officer of AVEO. "We are committed to maximizing the full potential of tivozanib both as a monotherapy and in the immunotherapy combination setting. We remain hopeful that the overall survival hazard ratio will continue to improve ahead of the final readout, expected in June 2020."

"This agent has shown in clinical trials to be effective in delaying cancer growth beyond established standards for patients who have returning kidney cancer," said Sumanta Pal, MD, a medical oncologist at City of Hope and co-lead author of the new study. "Although there are many options for patients with kidney cancer today, most are intended for first- and second-line therapy. We need a treatment that works for kidney cancer patients who have failed several lines of therapy."

AVEO recently provided a regulatory update following a meeting with the U.S. Food and Drug Administration (FDA) to discuss results from the August 2019 overall survival (OS) analysis of the TIVO-3 trial. The Company has submitted an update to the TIVO-3 statistical analysis plan to the FDA allowing for the final OS analysis to be conducted, intends to submit a New Drug Application (NDA) in the first quarter of 2020, and expects to report results from the final OS analysis in June 2020. The FDA and the Company agreed that if, during the review, the final analysis yields an OS HR above 1.00, the Company will withdraw its NDA. The FDA informed the Company that an Oncologic Drugs Advisory Committee panel would likely be convened to review the final tivozanib data package.

Results in Detail

Patients enrolled in the TIVO-3 trial (n=350) were randomized and stratified for prior regimen and IMDC prognostic score. Prior treatment regimens included prior checkpoint inhibitor and VEGF TKI therapies (n=91), two prior VEGF TKI therapies (n=159) and prior VEGF TKI and other therapies (n=100). Statistically significant improvements favoring tivozanib were reported for the primary endpoint of PFS (HR=0.73; p=0.0165) and secondary endpoint of overall response rate (18% vs. 8%; p=0.02).

As of the October 4, 2018 topline data analysis, in patients who received prior checkpoint inhibitor and VEGF TKI therapies, 29 PFS events occurred in the tivozanib group and 27 in the sorafenib group. Median PFS was 7.3 months with tivozanib and 5.1 months with sorafenib (HR 0.55, 95% CI 0.32–0.94). In this subpopulation, PFS at one year was 37% (95% CI 0.22–0.51) with tivozanib and 5% (0–0.14) with sorafenib. Two-year PFS was 28% (0.12–0.44) with tivozanib. No patients in the sorafenib subgroup were progression free at two years as of the October 4, 2018 data cutoff. In patients who had previously received two prior VEGF TKI therapies, 56 PFS events occurred in the tivozanib group and 61 occurred in the sorafenib group. Median PFS was 5.5 months tivozanib and 3.7 with sorafenib (HR 0.58, 95% CI 0.4–0.8).

For the secondary endpoint of OS, two prespecified analyses have been conducted, the first at a data cutoff date of October 4, 2018, and the second at August 15, 2019. The OS hazard ratio (HR), which assesses the relative risk of death for the entirety of the data set, was 0.99 (95% CI: 0.76-1.29; p=0.95) for the intent to treat population at the second analysis, an improvement from an HR of 1.12 observed at the first analysis.

As of the August 15, 2019 data cutoff date, median OS, a point in time value of the OS when half of the patients within each arm are still alive, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.7 months for sorafenib (95% CI: 15.0-24.2). As of the second data cutoff date, twenty patients remained progression free on the tivozanib arm and two on the sorafenib arm, with a median duration on study of 32.5 months.

Grade 3 or higher adverse events were consistent with those observed in previous tivozanib trials. Infrequent but severe adverse events reported in greater number in the tivozanib arm were thrombotic events similar to those observed in previous tivozanib studies. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib is being studied in the TIVO-3 trial, which is intended to support a regulatory submission of tivozanib in the U.S. as a treatment for relapsed/refractory RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.