On January 13, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported a three-way collaboration with Horizon Healthcare Services, Inc., New Jersey’s oldest and largest health insurer, and Clinical Outcomes Tracking and Analysis (COTA) to advance precision medicine, improve clinical outcomes and deliver enhanced value to the healthcare system in the treatment of patients with metastatic, non-small cell lung cancer (NSCLC) (Press release, Foundation Medicine, JAN 13, 2016, View Source [SID:1234508781]). The organizations initiated a prospective clinical study measuring changes in survival benefit and total cost savings achieved among patients with previously untreated metastatic NSCLC who undergo comprehensive genomic profiling with FoundationOne. Based on the outcomes, the study enables Horizon to provide its members with coverage for FoundationOne as a critical component of clinical care pathways in the evaluation of patients with metastatic lung cancer.

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As thought leaders and innovators in cancer care, the organizations designed the study to support guidelines from the National Comprehensive Cancer Network (NCCN) that specifically recommend broad molecular profiling for patients with NSCLC. These guidelines enable the identification of cancer-driving genomic alterations for which effective targeted therapies may already be approved and available commercially or to enable physicians to appropriately counsel patients regarding the availability of clinical trials. This recommendation by NCCN and the genesis of this trial supports the widespread understanding that cancer is a disease of the genome and that tumors may harbor specific genomic alterations likely to respond to "matched" therapies regardless of its anatomic site of origin.

FoundationOne is a comprehensive genomic profile (CGP) that enables physicians to make treatment decisions for patients with cancer by identifying the molecular growth drivers of their cancers and by helping oncologists match the identified drivers with relevant targeted therapeutic options. Requiring only a small amount of tumor tissue, FoundationOne interrogates the entire coding sequence of 315 cancer-related genes plus select introns from 28 genes that are known to be altered in solid tumors.

"We believe this study design, which embraces the importance of data sharing in molecular information, represents an innovative model of collaboration that will catalyze the consistent integration of comprehensive genomic profiling in clinical care for the treatment of metastatic lung cancer," stated Vincent Miller, M.D., chief medical officer for Foundation Medicine. "We fully expect the study to demonstrate the clinical and health economic benefits of a comprehensive approach versus the use of more limited testing panels and importantly, that these results will support broad reimbursement in this patient population with advanced disease," Miller added.

"Gene-by-gene testing, as is common practice today in metastatic NSCLC, presents clinical and logistical challenges, including missing alterations, insufficient tissue for testing, and a significant loss of precious time in identifying a clinical course of care," said Andrew Pecora, M.D., F.A.C.P., C.P.E., member of Regional Cancer Care Associates and chief innovation officer, Professor and vice president of Cancer Services, John Theurer Cancer Center at HackensackUMC. "The availability of a single CGP assay to accurately identify all known variants from a single sample and to accommodate the expanding list of genomic markers in metastatic NSCLC without necessitating new biopsies is a medical necessity."

"Horizon believes in investigating whether a comprehensive genomic approach could yield the most robust information to guide clinical treatment options – either to approved or investigational therapies – through clinical trials," said Glenn D. Pomerantz, M.D., JD, vice president and chief medical officer with Horizon. "Ultimately, we hope that working with Foundation Medicine on this approach will optimize outcomes for metastatic lung cancer patients."

Patients will be enrolled at Regional Cancer Care Associates (RCCA) and Hackensack Medical University in New Jersey. Patient outcomes will be tracked by Clinical Outcomes Tracking and Analysis (COTA). Horizon Blue Cross of New Jersey will pay for enrolled patients to receive FoundationOne assays as part of the study.

On January 11, 2016 FORMA Therapeutics and Cancer Research Technology, reported the formation of a third new virtual Asset Discovery and Development Company (ADDCos) with novel chemical matter targeting an undisclosed deubiquitinating enzyme (DUB) (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234509341]). ADDCos are virtual companies that rapidly advance drug discovery innovations in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

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This achievement is the result of an ongoing long-term initiative between FORMA and Cancer Research Technology, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under the agreement, FORMA is pairing its ultra-efficient drug discovery and early development capabilities with expertise from Cancer Research Technology’s Discovery Laboratories and the exclusive world-class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when aberrantly dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to represent highly attractive discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "The evolution of R&D across a distributed network of diverse scientific disciplines allows FORMA to rapidly and creatively advance research discoveries into clinical candidates."

Keith Blundy, CEO of Cancer Research Technology, said: "This partnership has proven to yield exciting biology and translational outcomes, when pairing complementary skills and capabilities together within a unique business structure. We look forward seeing such research discoveries develop into new medicines offering breakthrough treatments to cancer patients worldwide."

On January 12, 2016 FORMA Therapeutics report the initiation of a Phase 1 study of FT-1101, with the first dose administration in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234509342]). FT-1101 is an oral, structurally distinct and potent pan-inhibitor of the BET (Bromodomain and Extra-Terminal) epigenetic protein family.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome"

"The BET protein family represents an attractive group of therapeutic targets for a variety of liquid and solid tumors, as inhibition of these epigenetic binding proteins allows for selective effects on gene expression. FT-1101 is a novel, oral small molecule targeted against all four BET family members (BRD2, BRD3, BRD4, BRDT)," said John Hohneker, M.D., EVP and Head of Research and Development, FORMA Therapeutics. "The launch of this study is an important step for our team, and we are eager to begin the selection of preferred dosing schedules and potential patient populations in order to optimize activity and tolerability of this novel medicine."

Small molecule inhibition of BET results in down-regulation of the critical oncogene MYC, a master regulator of diverse cell functions critical for cell growth and survival in many cancers. At tolerated doses in human tumor xenograft mouse models, FT-1101 has demonstrated significant anti-tumor activity including tumor regressions.

FT-1101 is part of FORMA’s second global strategic collaboration with Celgene Corporation announced in April 2014. Celgene has obtained an exclusive EU license for FT-1101 in exchange for an undisclosed payment to FORMA. Under the terms of the collaboration agreement, FORMA will advance the FT-1101 program through Phase 1, and Celgene will be responsible to fund and execute further global clinical development.

"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome," said Guillermo Garcia-Manero, M.D., lead clinical investigator for FT-1101 at The University of Texas MD Anderson Cancer Center, Houston, TX, and Professor, Department of Leukemia, Division of Cancer Medicine.

On January 12, 2016 FORMA Therapeutics and Cancer Research Technology reported the formation of a third new virtual Asset Discovery and Development Company (ADDCos) with novel chemical matter targeting an undisclosed deubiquitinating enzyme (DUB) (Press release, Cancer Research Technology, DEC 12, 2016, View Source [SID1234523189]). ADDCos are virtual companies that rapidly advance drug discovery innovations in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This achievement is the result of an ongoing long-term initiative between FORMA and Cancer Research Technology, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under the agreement, FORMA is pairing its ultra-efficient drug discovery and early development capabilities with expertise from Cancer Research Technology’s Discovery Laboratories (CRT-DL) and the exclusive world-class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to represent highly attractive discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "The evolution of R&D across a distributed network of diverse scientific disciplines allows FORMA to rapidly and creatively advance research discoveries into clinical candidates."

Keith Blundy, CEO of Cancer Research Technology, said: "This partnership has proven to yield exciting biology and translational outcomes, when pairing complementary skills and capabilities together within a unique business structure. We look forward seeing such research discoveries develop into new medicines offering breakthrough treatments to cancer patients worldwide."

On January 12, 2016 FORMA Therapeutics reported the initiation of a Phase 1 study of FT-1101, with the first dose administration in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234511394]). FT-1101 is an oral, structurally distinct and potent pan-inhibitor of the BET (Bromodomain and Extra-Terminal) epigenetic protein family.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome"
"The BET protein family represents an attractive group of therapeutic targets for a variety of liquid and solid tumors, as inhibition of these epigenetic binding proteins allows for selective effects on gene expression. FT-1101 is a novel, oral small molecule targeted against all four BET family members (BRD2, BRD3, BRD4, BRDT)," said John Hohneker, M.D., EVP and Head of Research and Development, FORMA Therapeutics. "The launch of this study is an important step for our team, and we are eager to begin the selection of preferred dosing schedules and potential patient populations in order to optimize activity and tolerability of this novel medicine."

Small molecule inhibition of BET results in down-regulation of the critical oncogene MYC, a master regulator of diverse cell functions critical for cell growth and survival in many cancers. At tolerated doses in human tumor xenograft mouse models, FT-1101 has demonstrated significant anti-tumor activity including tumor regressions.

FT-1101 is part of FORMA’s second global strategic collaboration with Celgene Corporation announced in April 2014. Celgene has obtained an exclusive EU license for FT-1101 in exchange for an undisclosed payment to FORMA. Under the terms of the collaboration agreement, FORMA will advance the FT-1101 program through Phase 1, and Celgene will be responsible to fund and execute further global clinical development.

"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome," said Guillermo Garcia-Manero, M.D., lead clinical investigator for FT-1101 at The University of Texas MD Anderson Cancer Center, Houston, TX, and Professor, Department of Leukemia, Division of Cancer Medicine.

About the Study

The Phase 1 multicenter, open-label, dose escalation clinical trial is designed to assess the safety and tolerability of FT-1101 capsules as a single agent. FT-1101 will be administered orally on a once weekly dosing schedule in a 28-day cycle. The study will enroll patients with relapsed refractory AML and high risk myelodysplastic syndrome. Key objectives in the study include determination of a maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of FT-1101. Please refer to www.clinicaltrials.gov for additional clinical trial details.

About BET

The Bromodomain and Extra-Terminal (BET) family of bromodomain-containing proteins (BRD2, BRD3, BRD4, and BRDT) regulate chromatin structure and gene expression through their ability to bind to acetylated lysine residues on histone tails and act as epigenetic readers. In particular, BRD4 has been shown to positively regulate the expression of MYC and other critical cancer-associated genes through the localization of BRD4 to super-enhancer regulatory elements. Preclinical studies conducted using BET inhibitors and emerging data from ongoing clinical trials in leukemia and lymphoma patients, have provided initial support for the therapeutic potential of BET inhibitors in hematologic malignancies.