On December 8, 2017 VistaGen Therapeutics Inc. (NASDAQ: VTGN), a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders, reported that the U.S. Patent and Trademark Office (USPTO) has issued U.S. Patent No. 9,834,754 related to methods for producing, from human pluripotent stem cells (hPSCs), hematopoietic precursor stem cells, which are stem cells that give rise to all of the blood cells and most of the bone marrow cells in the body (Press release, VistaGen Therapeutics, DEC 8, 2017, View Source [SID1234522475]). VistaGen holds an exclusive license to this patent from the University Health Network (UHN).

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The technology covered by the issued U.S. patent has the potential to impact both direct and supportive therapy for autoimmune disorders and cancer, with CAR-T cell applications, and foundational technology which may provide approaches for producing bone marrow stem cells for bone marrow transfusions.

Dr. Gordon Keller, Director of the McEwen Centre for Regenerative Medicine in Toronto, one of the world’s leading centers for stem cell and regenerative medicine research and part of the University Health Network (UHN), discovered the stem cell technology covered by this patent.

On December 8, 2017 Pfizer Inc. (NYSE:PFE) reported that the Phase 3 EMBRACA trial in patients with germline (inherited) BRCA1/2-positive (gBRCA+) locally advanced and/or metastatic breast cancer (MBC) demonstrated superior progression-free survival (PFS) in patients treated with talazoparib, compared to patients who received physician’s choice standard of care chemotherapy (Press release, Pfizer, DEC 8, 2017, View Source [SID1234522470]). Median PFS was 8.6 months (95% CI: 7.2, 9.3) for patients treated with talazoparib and 5.6 months (95% CI: 4.2, 6.7) for those treated with chemotherapy [HR: 0.54 (95% CI: 0.41, 0.71), p<0.0001]. This represents a 46% reduction in the risk of disease progression. In addition, the proportion of patients achieving a complete or partial response (objective response rate) in the talazoparib group was more than twice that of the control arm (62.6% for talazoparib vs. 27.2% for chemotherapy [OR: 4.99 (95% CI: 2.9-8.8), p<0.0001]). Talazoparib is an investigational, oral, dual-mechanism poly ADP ribose polymerase (PARP) inhibitor that is taken once daily. The data will be presented today as an oral presentation at the 2017 San Antonio Breast Cancer Symposium.

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"Patients with germline BRCA-positive breast cancer are typically diagnosed at a younger age than those with nonhereditary breast cancer, and there are no therapies specifically approved for them outside of current standard of care therapies," said Jennifer Litton, MD, lead investigator and associate professor in the breast medical oncology department of The University of Texas MD Anderson Cancer Center. "EMBRACA supports the potential of talazoparib to give these patients additional time without disease progression, compared to chemotherapy."

Pfizer will be discussing these data from EMBRACA, the largest Phase 3 trial performed to date of a PARP inhibitor in patients with gBRCA+ MBC, with worldwide health authorities. There are currently limited treatment options for patients with this molecular subtype.

"Results from the EMBRACA study are very encouraging and a great example of precision drug development. By enrolling only patients with germline BRCA-positive metastatic breast cancer, treatment with talazoparib reduced the risk of disease worsening by nearly half, compared with current standard of care chemotherapy. This includes heavily pretreated patients, those with hormone receptor-positive disease and those who had a history of brain metastases," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development.

The results of the EMBRACA trial also showed that the PFS benefit with talazoparib was consistent across prespecified subgroups, including hormone receptor (HR) status (triple negative [TNBC] or hormone receptor-positive [HR+]), BRCA mutation (1 or 2), prior chemotherapy (whether patients had none or up to three chemotherapies before talazoparib), and history of central nervous system (CNS) metastases. There also was a statistically significant delay in the time to clinically meaningful deterioration in global health status/quality of life with talazoparib versus chemotherapy (HR 0.38 [95% CI 0.26-0.55], p<0.0001), as measured by the EORTC QLQ-C30, a cancer-specific, patient-reported quality of life questionnaire.

Adverse events (AEs) observed with talazoparib were consistent with findings from previous trials. The most common AEs observed with talazoparib (any grade in at least 15% of patients) were anemia (52.8%), fatigue (50.3%), nausea (48.6%), neutropenia (34.6%), headache (32.5%), thrombocytopenia (26.9%), alopecia (25.2%), vomiting (24.8%), diarrhea (22%), constipation (22%), decreased appetite (21.3%), back pain (21%) and dyspnea (17.5%). The incidence of serious AEs was 31.8% in the talazoparib arm and 29.4% in the chemotherapy arm. Discontinuations due to AEs occurred in 7.7% of patients in the talazoparib arm and 9.5% of patients in the chemotherapy arm.

In addition to EMBRACA, talazoparib demonstrated promising activity in patients with gBRCA+ MBC in the Phase 2 ABRAZO trial. Patients in ABRAZO had either been previously treated with platinum-based chemotherapy or were heavily pretreated with at least three prior lines of non-platinum-based chemotherapy.1

About EMBRACA

EMBRACA is a global Phase 3, open-label, randomized, parallel, 2-arm trial of talazoparib versus protocol-specific physician’s choice of standard single-agent chemotherapy (PCT [capecitabine, eribulin, gemcitabine or vinorelbine]) in gBRCA+ patients who may have received up to three prior cytotoxic chemotherapy regimens for locally advanced and/or metastatic breast cancer. Patients enrolled had a diagnosis of TNBC or HR+/HER2-negative breast cancer. The trial randomized (2:1) 431 patients to receive talazoparib (1.0 mg) once daily or PCT.

About Germline BRCA1/2-Positive Breast Cancer

BRCA1 and BRCA2 are human genes that produce proteins involved in DNA repair. When either of these genes is altered or mutated, DNA repair may not progress correctly. This can lead to the development of certain types of cancer such as breast cancer.2,3,4 BRCA mutations can be hereditary (germline) or occur spontaneously (sporadic).2 Together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers.5,6 Up to 65 percent of women who inherit a BRCA mutation will develop breast cancer by age 70.2 Epidemiologic studies indicate that individuals with gBRCA+ status are diagnosed with breast cancer at a median age of 40-45, which is approximately 20 years younger than the overall breast cancer population.7

About Talazoparib

Talazoparib is an investigational anti-cancer compound called a PARP (poly ADP ribose polymerase) inhibitor. Preclinical studies suggest that talazoparib is highly potent and has a dual mechanism of action, with the potential to induce tumor cell death by blocking PARP enzyme activity and trapping PARP on the sites of DNA damage. Talazoparib is currently being evaluated in advanced gBRCA+ breast cancer as well as other cancer types with deficiencies in DNA damage repair (DDR). It is also being studied in DDR-deficient prostate cancer and in combination with immunotherapy in various tumor types. Talazoparib has not been approved by any regulatory authorities for the treatment of any disease.

On December 8, 2017 Personalis, Inc., a leading provider of advanced genomic sequencing and analytics to support the development of personalized cancer vaccines and other next-generation cancer immunotherapies, reported that the company’s Chief Scientific Officer (CSO), Dr. Richard Chen, will be speaking at the upcoming Neoantigen Summit, being held in Boston, MA from November 14-16, 2017 (Press release, Personalis, DEC 8, 2017, View Source [SID1234522469]).

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The presentation entitled, "From Sample to Neoantigens for Vaccines: Key Challenges and Solutions" will cover topics including:

cfDNA Neoantigens: dealing with tumor heterogeneity
Improving neoantigen identification
Elaborating tumor microenvironment (TME), immuno-modulators and vaccine response biomarkers
Overcoming poor sample quality and quantity for NGS sequencing
Addressing sequencing coverage gaps that can harbor neoantigens
Validation and regulatory issues on the way to commercialization
Central to this presentation will be Personalis’ ACE ImmunoID Platform. The platform enables the comprehensive characterization of a tumor’s immuno-genomics including neoantigens, the tumor microenvironment, HLA, immuno-modulators and mechanisms of tumor escape to aid rational vaccine design.

"We are continuing to innovate to help our customers build safe, effective, and scalable personalized cancer vaccines. In this talk we will discuss how our ACE ImmunoID platform has been designed to overcome key challenges in personalized cancer vaccine development process starting from a tumor sample to neoantigen identification and rational vaccine design," said Dr. Richard Chen, CSO at Personalis.

Personalis will also be exhibiting during the Neoantigen Summit. Representatives will be available to answer questions about the company’s neoantigen identification and immuno-genomics capabilities.

On December 8, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported new results from two studies with EndoPredict are being featured at the 2017 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas (Press release, Myriad Genetics, DEC 8, 2017, View Source [SID1234522466]). EndoPredict is a second-generation prognostic gene expression test for patients with breast cancer.

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"We are excited to present new data on our EndoPredict test which demonstrates our ongoing commitment to collaborate with leading academic research centers and advance personalized medicine for patients with breast cancer," said Ralf Kronenwett, M.D., Ph.D., director of International Medical Affairs, Myriad Genetics. "Importantly, these new studies add to the expanding body of evidence demonstrating how EndoPredict can be used to predict both disease recurrence as well as response to therapy."
The data are highlighted below and abstracts are available at: View Source Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #SABCS17.

EndoPredict Podium Presentation
Title: The EndoPredict score predicts residual cancer burden to neoadjuvant chemotherapy and to neuroendocrine therapy in HR+/HER2- breast cancer patients from ABCSG34.
Presenter: Peter Dubsky, M.D., Medical University of Vienna, Austria and the Breast Center St. Anna Klinik, Lucerne.
Date: Friday, Dec. 8, 2017, 3:15—5:00 p.m.
Location: Podium, GS6-04

This study was designed to show the predictive value of the EndoPredict (EP) 12-gene molecular score for tumor response to neoadjuvant chemotherapy and neoendocrine therapy. The study included biopsies from 217 women with HR+ breast cancer. Of these, 134 patients were assigned to receive neoadjuvant chemotherapy according to aggressive clinico-pathologic tumor features. The remaining 83 patients were clinically identified as having luminal A types of breast cancer and were assigned to receive neoendocrine treatment. The primary endpoint was residual cancer burden RCB0/I (i.e., good tumor response) vs. RCB II/III (i.e., poor tumor response) at time of surgery.
In the neoadjuvant chemotherapy group, 125 patients had high EP scores and nine had a low EP score. The results show that 26.4 percent of those with a high score showed a good tumor response (RCB0/I) to neoadjuvant chemotherapy, while all patients with a low score showed only a poor tumor response (Table 1). In the "luminal A" group receiving neoendocrine therapy, 39 patients had a high EP score and 44 had a low EP score. The results show that 27.3 percent of those with a low EndoPredict score and 7.7 percent with a high score achieved excellent tumor response (RCB0/I) to neoendocrine therapy (Table 1).

Table. 1 EndoPredict
Low Score EndoPredict
High Score
p-Value
Response to
Neoadjuvant
Chemotherapy 0.0 % 26.4 % p=0.0001
Response to
Endocrine Therapy 27.3 % 7.7 % P=0.015

"This exciting study is evidence that women with a high EP score responded better to neoadjuvant chemotherapy than those with a low score, while those with a low EndoPredict score responded better to neoadjuvant endocrine therapy," said Peter Dubsky, M.D., principal investigator, speaking on behalf of the Austrian Breast and Colorectal Cancer Study Group (ABCSG). "These findings are relevant to better patient selection for biomarker driven studies in the neoadjuvant setting."

EndoPredict Poster Presentation
Title: The role of EndoPredict in invasive lobular carcinoma.
Presenter: Ivana Sestak, Ph.D., Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London.
Date: Thursday, Dec. 7, 2017, 5:00—7:00 p.m.
Location: Poster, P3-08-01

This study evaluated the role of EndoPredict molecular-clinical score (EPclin) for the prediction of distant recurrence in women diagnosed with invasive lobular carcinoma (ILC) compared to those with invasive ductal carcinoma (IDC). The study included 928 women with E R+/HER2- breast cancer: 141 had ILC, 710 had IDC and 77 were mixed type.
This result shows that EndoPredict provided significant power for predicting distant recurrence in patients with both ILC (EPclin: LR-X2=5.8) and IDC (EPclin: LR-X2=13.8). Women with ILC who had a high EPclin score were at seven times increased risk of 10-year distant recurrence with endocrine therapy only than patients with low EPclin score. In comparison, women with IDC who had a high EPclin score were at five times increased risk of 10-year recurrence than patients with low EPclin score. Importantly, there was a similar 10-year distant recurrence risk in patients with a low EPclin score (~6 percent), which suggests that chemotherapy is not indicated in these patients with a low risk score regardless of tumor type.
"Our results show that EndoPredict provided highly significant prognostic information and risk stratification in women with invasive lobular carcinoma," said Ivana Sestak, Ph.D., principal investigator, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London. "Importantly, the 10-year risk of distant recurrence in the EndoPredict low-risk groups was similar between ILC and IDC, suggesting that chemotherapy is not indicated for these patients, irrespective of tumor type."

About EndoPredict
EndoPredict is a second-generation, multigene prognostic test for patients diagnosed with breast cancer. The test provides physicians with information to devise personalized treatment plans for their patients. EndoPredict has been validated in approximately 4,000 patients with node-negative and node-positive cancer and has been used clinically in more than 20,000 patients. In contrast to first-generation multigene prognostic tests, EndoPredict detects the likelihood of late metastases (i.e., metastasis formation after more than five years) and, therefore, can guide treatment decisions regarding the need for chemotherapy, as well as extended anti-hormonal therapy. Accordingly, therapy decisions backed by EndoPredict confer a high level of diagnostic safety. For more information, please visit: www.endopredict.com.

On December 8, 217 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that the first subject has been treated in the APOLLO study of FATE-NK100 in women with ovarian cancer resistant to, or recurrent on, platinum-based treatment (Press release, Fate Therapeutics, DEC 8, 2017, View Source [SID1234522461]). The clinical trial is intended to evaluate the safety and determine the maximum dose of FATE-NK100, the Company’s first-in-class, donor-derived adaptive memory natural killer (NK) cell cancer therapy, as a monotherapy when administered intraperitoneally in the outpatient setting. A clinical assessment of patients with ovarian cancer has previously shown that endogenous NK cells within the peritoneal fluid exhibit an altered phenotype with reduced cytolytic function.

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"Women today often are treated with intraperitoneal chemotherapy, and the administration of FATE-NK100 directly within the peritoneal cavity is an exciting therapeutic strategy to restore NK cell function, promote persistence and inhibit tumor growth," said Melissa A. Geller, M.D., Associate Professor in the Department of Obstetrics, Gynecology and Women’s Health, Division of Gynecologic Oncology at the University of Minnesota and the lead investigator of the clinical trial at the Masonic Cancer Center. "Ovarian cancer is a disease of middle age women, and over 60% of women with ovarian cancer initially present with advanced disease. For these women, the rate of recurrence is around 70%, and there is an urgent need for novel therapeutic strategies since standard treatments in the recurrent setting provide dismal response rates especially in platinum resistant disease."

The APOLLO study is an open-label, accelerated dose-escalation, Phase 1 clinical trial of FATE-NK100 in subjects with recurrent ovarian, fallopian tube or primary peritoneal cancer. Up to three dose levels of FATE-NK100 are intended to be assessed to evaluate safety and determine the maximum dose. Other endpoints to be evaluated include objective response rate at 28 days, and progression-free and overall survival at six months. Subjects with stable disease or better at Day 28 following infusion may be considered for retreatment with FATE-NK100.

Ovarian cancer is the fifth leading cause of cancer-related death among women, and is the deadliest of gynecologic cancers. The American Cancer Society estimates that in 2017, about 22,440 new cases of ovarian cancer will be diagnosed and 14,080 women will die of ovarian cancer in the United States. While a high proportion of women respond to initial platinum-based chemotherapy, around 70% of patients diagnosed with ovarian cancer will have a recurrence. While recurrent ovarian cancer is treatable, it is rarely curable and there is a significant need for more effective, better-tolerated therapies.

About FATE-NK100
FATE-NK100 is a first-in-class, donor-derived natural killer (NK) cell cancer immunotherapy comprised of adaptive memory NK cells, a highly specialized and functionally distinct subset of activated NK cells expressing the maturation marker CD57. Higher frequencies of CD57+ NK cells in the peripheral blood or tumor microenvironment in cancer patients have been linked to better clinical outcomes. In preclinical studies, FATE-NK100 has demonstrated enhanced anti-tumor activity across a broad range of hematologic and solid tumors, with augmented cytokine production, improved persistence and increased resistance to immune checkpoint pathways compared to other NK cell therapies that are being clinically administered today. FATE-NK100 is produced through a feeder-free, seven-day manufacturing process during which NK cells sourced from a healthy donor are activated ex vivo with pharmacologic modulators.

About APOLLO
APOLLO is an open-label, accelerated dose-escalation, Phase 1 clinical trial in subjects with recurrent ovarian, fallopian tube or primary peritoneal cancer designed to evaluate the safety and determine the maximum dose of a single infusion of FATE-NK100 as a monotherapy when administered via intraperitoneal catheter after out-patient chemotherapy followed by sub-cutaneous IL-2 administration. Up to three dose levels of FATE-NK100 are intended to be assessed (1×107 cells/kg, >1×107 cells/kg to ≤3×107 cells/kg, and up to 1×108 cells/kg). In the event a dose limiting toxicity is observed, the clinical trial will convert to a 3+3 design. A ten-subject expansion cohort is expected to be enrolled at the maximum dose level. Other endpoints include objective response rate at 28 days, and progression-free and overall survival at six months, post-infusion of FATE-NK100. The clinical trial is being conducted at the Masonic Cancer Center, University of Minnesota as an investigator-initiated study.