Myovant Sciences has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Myovant Sciences, 2017, NOV 13, 2017, View Source [SID1234522024]).

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On November 13, 2017 CymaBay Therapeutics, Inc. (NASDAQ:CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported that management will provide a corporate overview at the 29th Annual Piper Jaffray Healthcare Conference, the Evercore/ISI 2017 Biopharma Catalyst/Deep Dive Conference, and the Global Mizuho Investor Conference (Press release, CymaBay Therapeutics, NOV 13, 2017, View Source [SID1234521961]).

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29th Annual Piper Jaffray Healthcare Conference
Date: Wednesday, November 29
Time: 12:00pm Eastern time
Location: Lotte New York Palace Hotel
Webcast: View Source;

Evercore/ISI 2017 Biopharma Catalyst/Deep Dive Conference
Date: Thursday, November 30
Time: 12:05pm Eastern Time
Location: Boston Harbor Hotel
Webcast: View Source;

Global Mizuho Investor Conference
Date: Tuesday, December 5
Time: One-on-One Format
Location: Lotte New York Palace Hotel

On November 13, 2017 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company applying synthetic biology to probiotics to develop novel, living medicines, reported its financial results for the third quarter ended September 30, 2017. As of September 30, 2017, Synlogic had cash, cash equivalents, and short-term investments of $96.6 million (Press release, Synlogic, NOV 13, 2017, View Source [SID1234522011]).

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"In our first months as a public company, we have achieved significant progress in advancing our pipeline with our recent release of positive data from the first clinical trial of our Synthetic Biotic medicine SYNB1020 for hyperammonemia," said JC Gutiérrez-Ramos, Ph.D., Synlogic’s president and chief executive officer. "We are building an organization with the goal of bringing rational drug design and pharmacologically driven drug development to a new class of living medicines. We are focused internally on developing treatments for inborn errors of metabolism and we look forward to advancing our two lead programs into clinical studies in patients in 2018."

Pipeline Highlights

Reported positive top-line clinical data from Synlogic’s Phase 1 clinical study of SYNB1020, an orally delivered, first-in-class, Synthetic Biotic medicine designed to treat elevated blood ammonia levels (hyperammonemia) in genetic urea cycle disorders (UCD) or in chronic liver disease
The trial successfully met its primary objectives, demonstrating safety and tolerability in healthy volunteers and identifying the maximum tolerated dose. SYNB1020 did not colonize and was cleared within the expected timeframe in subjects who had completed follow-up. Viability and evidence of mechanistic activity of the Synthetic Biotic was demonstrated in feces of subjects who received SYNB1020, but not in control subjects. Furthermore, in the multiple ascending dose component of the Phase 1 study, daily dosing of SYNB1020 over 14 days in healthy volunteers enabled identification of a dose-response relationship between SYNB1020 oral administration and changes in a nitrogen endpoint in plasma which was found to be statistically significant in the highest dose cohort compared to placebo
The Company plans to initiate a Phase 1b/2a study of SYNB1020 in patients with liver cirrhosis and elevated ammonia in the first half of 2018 and a second Phase 1b/2a study in patients with UCDs.
Received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for SYNB1618, an orally delivered, Synthetic Biotic medicine designed for treatment of phenylketonuria (PKU), an inborn error of metabolism caused by a mutation of the gene that breaks down the amino acid phenylalanine (Phe).
Reserved for treatments of rare diseases affecting fewer than 200,000 people in the U.S., Orphan Drug Designation offers FDA assistance in trial design and grants development and commercial incentives, including eligibility for a seven-year period of market exclusivity in the U.S., if approved. In 2018, Synlogic plans to initiate a clinical trial to evaluate SYNB1618 for the potential treatment of PKU.
Corporate Highlights

Completed merger and began trading on the NASDAQ Capital Market under the ticker symbol "SYBX".
On August 28, 2017, Synlogic, Inc. and Mirna Therapeutics, Inc. closed the merger of the two companies.
Strengthened leadership team with two key additions.
Synlogic appointed two experienced executives to key leadership roles: Andrew Gengos as Chief Operating Officer and Head of Corporate Development; and Adam Thomas as Chief Human Resources Officer.
Third Quarter 2017 Financial Results

As of September 30, 2017, Synlogic had cash, cash equivalents, and short-term investments of $96.6 million and 16.3 million shares issued and outstanding.

For the three months ended September 30, 2017, Synlogic reported a net loss of $11.9 million for the third quarter of 2017 compared to a net loss of $5.3 million for the corresponding period in 2016. The increase in net loss for the third quarter was primarily due to increases in research and development expenses as well as increases in compensation-related expenses as Synlogic continues to grow its employee headcount and hire into key positions to support its corporate goals.

Research and development expenses were $9.0 million for the three months ended September 30, 2017 compared to $4.1 million in the corresponding period in 2016. The increase was primarily due to an increase in external costs associated with our Phase 1 clinical trial, preclinical studies, formulation development and consulting fees as well as increased internal research costs and increased compensation-related expenses associated with increased headcount.

General and administrative expenses for the three months ended September 30, 2017 were $3.2 million compared to $1.3 million for the corresponding period in 2016. The increase was primarily due to increases in expenses related to the reverse merger and becoming a public company including legal, audit, investor relations, and filing fees as well as increases in compensation-related expenses associated with increased headcount.

Revenue was $0.1 million for each of the three months ended September 30, 2017 and September 30, 2016. Revenue is associated with the upfront, nonrefundable $2.0 million payment from the AbbVie collaboration, which is being recognized on a straight-line basis over the expected term of the collaboration.

About Synthetic Biotic Medicines

Synlogic’s innovative new class of Synthetic Biotic medicines leverages the tools and principles of synthetic biology to genetically engineer probiotic microbes to perform or deliver critical functions missing or damaged due to disease. The company’s two lead programs target a group of rare metabolic diseases – inborn errors of metabolism (IEM). Patients with these diseases are born with a faulty gene, inhibiting the body’s ability to break down commonly occurring by-products of digestion that then accumulate to toxic levels and cause serious health consequences. When delivered orally, these medicines can act from the gut to compensate for the dysfunctional metabolic pathway and have a systemic effect. Synthetic Biotic medicines are designed to clear toxic metabolites associated with specific metabolic diseases and have the potential to significantly improve symptoms of disease for affected patients.

On November 13, 2017 Array BioPharma Inc. (Nasdaq: ARRY), a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule cancer therapies, reported data from the Phase 1b clinical trial evaluating the immunotherapy combination of ARRY-382, with Merck’s KEYTRUDA (pembrolizumab), an anti-PD-1 antibody, in patients with certain advanced solid tumors, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting, being held Nov. 8-12, 2017 in National Harbor, Maryland (Press release, Array BioPharma, NOV 13, 2017, View Source;p=RssLanding&cat=news&id=2316453 [SID1234521957]). ARRY-382 is a highly selective oral inhibitor of the CSF1R kinase and would be among the first investigational compounds targeting this pathway.

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"We are pleased to announce completion of the Phase 1b clinical study of ARRY-382 in combination with KEYTRUDA. In addition to establishing an appropriate Phase 2 dose for the combination, we are encouraged by the early signs of activity in patients with tumor types that have been historically unresponsive to anti-PD1 therapies," said Ron Squarer, Chief Executive Officer, Array BioPharma.

In the Phase 1b dose escalation trial, the recommended Phase 2 dose of ARRY-382 was determined to be 300 mg daily in combination with KEYTRUDA 2 mg/kg given intravenously every 3 weeks.

Nineteen patients, with a median of two prior lines of therapy and 42% with ≥3 prior regimens, were treated in the study. Patients with pancreatic (n=6), colorectal (n=5), ovarian (n=3), gastric and melanoma (n=2, each), and triple negative breast cancer (n=1) were enrolled. Investigators noted that ARRY-382 had a manageable safety profile when administered with KEYTRUDA in this study, and the most common grade 3/4 adverse events (AEs) (>10%), regardless of causality, included increased AST, increased blood creatine kinase (CK), rash, increased lipase, increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT) and anemia.

The combination of ARRY-382 and KEYTRUDA demonstrated early signs of activity, with 11% (n=2) of patients achieving a confirmed partial response, based on RECIST version 1.1 guidelines The first responder, who was treated with ARRY-382 at 200 mg, had Stage III pancreatic ductal adenocarcinoma. As of the data cut-off, this patient was on study treatment in cycle 14 (42 weeks). The second responder, who was treated with ARRY-382 at 300 mg, had stage IV ovarian cancer with liver metastasis. As of the data cut-off, this patient was on study treatment in cycle 8 (24 weeks).

The current trial was designed to enroll Phase 2 cohorts in both melanoma and non-small cell lung cancer patients, and now Array plans to expand the study to include other patient populations, including a cohort of pancreatic cancer patients. The Phase 2 portion of the study is currently active and enrolling patients.

About CSF1R and ARRY-382

Colony-stimulating factor 1 receptor (CSF1R) is a cell-surface receptor for its ligands, colony-stimulating factor 1 (CSF1) and IL-34.[1, 2] CSF1R is thought to play an important role as regulator of the development, morphology, survival, and functions of tissue macrophages as well as tumor-associated macrophages (TAMs). TAMs play a role in modulating anti-tumor adaptive immunity and CSF1 is believed to be a driver of TAM differentiation towards an immunosuppressive tumor promoting phenotype. Increased CSF1 expression is implicated in tumor progression and metastasis, and is associated with poor prognosis in some cancers.[3] Combining a PD-1 inhibitor with a CSF1R inhibitor in preclinical models shows enhanced antitumor activity. ARRY-382 is a highly selective, oral inhibitor of CSF1R.

On November 13, 2017 Mirati Therapeutics, Inc. (Nasdaq: MRTX) (the Company or Mirati), a clinical-stage targeted oncology company, reported that it is reprioritizing its development programs to capitalize on encouraging data and development opportunities in its sitravatinib and KRAS programs (Press release, Mirati, NOV 13, 2017, View Source [SID1234522006]). In addition, the Company announced that it has selected a clinical lead and backup compounds in its KRAS program that potently target KRAS G12C mutations. An Investigational New Drug (IND) Application submission is expected by the fourth quarter of 2018. The Company also announced it will deprioritize further investment in glesatinib and will pursue opportunities to partner the program. The reallocation of resources will support the acceleration and expansion of the sitravatinib and KRAS programs and is expected to provide funding for operations into late 2019.

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"We are very encouraged by the early results from our sitravatinib immuno-oncology program. The combination of sitravatinib and nivolumab has demonstrated durable responses and prolonged stable disease in patients with non-small cell lung cancer that have documented progression on prior checkpoint therapy. This is a patient population with poor prognosis and limited treatment options. We are focusing on accelerating this promising opportunity with sitravatinib and advancing our potentially first-in-class KRAS program, both of which address large underserved patient populations with significant market potential," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer.

Program updates the Company expects to provide in 2018 include:
•
Phase 2 data from the immuno-oncology combination of sitravatinib and nivolumab in patients with checkpoint refractory non-small cell lung cancer (NSCLC) by mid-2018.
•
Advancement of the potentially first-in-class KRAS G12C inhibitor program to an IND submission by the fourth quarter of 2018.
•
Phase 1b proof-of-concept data from the study of sitravatinib as a single agent in genetically selected patients with NSCLC and other solid tumors by mid-2018.

•
Phase 2 data from the immuno-oncology combination of mocetinostat and durvalumab in patients with checkpoint refractory NSCLC in the first quarter of 2018.

Mirati’s Development Programs

Sitravatinib

Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being tested in combination with the anti-PD-1 checkpoint inhibitor, nivolumab (OPDIVO), in NSCLC patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. The majority of NSCLC patients either do not respond to checkpoint therapy or experience disease progression following treatment. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.

As previously reported at the IASLC 18th World Conference on Lung Cancer, initial data from the ongoing Phase 2 study of sitravatinib in combination with nivolumab included three confirmed Partial Responses (PRs) in the first 11 evaluable patients. Eight of these patients exhibited tumor reduction. Seven patients (including all three patients with PRs) remained on study, with treatment duration ranging from four months to 10.5 months. These initial results are encouraging and may extend to other tumor types, including renal cell, bladder and liver cancer, where checkpoint inhibitors have demonstrated efficacy that may potentially be expanded by combining with sitravatinib. The Company plans to provide an update on the first two stages of this trial in up to 34 patients by mid-2018.

Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion trial enrolling patients whose tumors harbor CBL, CHR4Q12 and RET genetic alterations in NSCLC and other tumor types. In the ongoing Phase 1b study of sitravatinib as a single agent, an objective response with tumor reduction of 77% was observed in the first evaluable NSCLC patient with a CBL mutation. The Company continues to enroll patients in this trial to confirm this early promising activity and will provide a further update across all cohorts by mid-2018.

KRAS Program Advancing Towards IND in 2018

The Company has selected a clinical lead and backup compounds for advancement to IND in its potential first-in-class KRAS program. The KRAS program emerged from a joint drug discovery collaboration with Array BioPharma, where over 100 co-crystal structures provided critical insight toward the design of potent and selective KRAS inhibitors. The clinical lead and backups are orally-available small molecule inhibitors of KRAS G12C mutations, with potencies of 1 to 20 nM (cellular IC50) and selectivity of greater than 1,000-fold for target inhibition in tumor cells harboring KRAS G12C mutations compared with cells exhibiting wild-type KRAS. In addition, the clinical lead and backups demonstrated complete regression of KRAS G12C-positive tumors implanted in mice. IND-enabling preclinical studies are underway, and an IND submission is expected by the fourth quarter of 2018, with early clinical proof-of-concept anticipated in 2019.

Historically, KRAS has been extremely difficult to directly inhibit due to its high affinity for GTP, and its lack of a defined binding pocket. Tumors characterized by KRAS mutations are commonly associated with poor prognosis and resistance to therapy. KRAS G12C driver mutations occur in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients, who

have few treatment options. The Company’s KRAS program has the potential to be the first direct inhibitor of this important and challenging tumor driver mutation.

Mocetinostat

Mocetinostat is a selective Class I and IV HDAC inhibitor. Inhibition of histone acetylation is predicted to enhance the recognition of tumor cells by anti-tumor T cells and reverse immunosuppressive factors in the tumor microenvironment. The Company is conducting a Phase 2 study of mocetinostat in combination with durvalumab (IMFINZI) in NSCLC patients who have experienced disease progression after prior treatment with checkpoint inhibitor therapy. Patients are stratified into two cohorts based upon their best response to prior checkpoint therapy. Stage 1 of the study is currently enrolling nine patients in each cohort. As previously reported, one cohort has already met the prespecified criteria for expansion into stage 2 with at least one confirmed partial response. The Company will provide an update on this trial in the first quarter of 2018.

Glesatinib
Glesatinib has demonstrated clinical activity and acceptable tolerability in MET-altered NSCLC patients. However, in light of superior investment opportunities in its pipeline, the Company will suspend further investment in glesatinib and will pursue opportunities to partner the program. The Company intends to present glesatinib data at a future medical conference.

LSD1 Preclinical Program
The Company has elected to suspend further development of its preclinical LSD1 inhibitor program as part of its reprioritization. In light of superior investment opportunities in its pipeline, the Company will seek a partner to continue development of the program.