On November 13, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported the submission of its Phase I/II clinical trial protocol to the U.S. Food and Drug Administration (FDA) for GEN-1, the Company’s DNA-based immunotherapy for the localized treatment of ovarian cancer (Press release, Celsion, NOV 13, 2017, View Source [SID1234521999]). The protocol, developed in conjunction with guidance from the Company’s Medical Advisory Board, is designed with a single dose escalation to evaluate the safety and biological activity of GEN-1 at 100mg/m² in newly diagnosed Stage III/IV ovarian cancer patients, followed by a continuation at the selected dose in Phase II in a 90 patient 1 to 1 randomized study. GEN-1 has demonstrated encouraging safety and efficacy data in a recently completed dose escalating Phase IB trial in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients received escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, followed by interval debulking surgery.

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"GEN-1 is designed to locally activate IL-12 production which can recruit and stimulate the patient’s immune system to attack and destroy cancer," stated Dr. Nicolas Borys, Celsion’s senior vice president and chief medical officer. "In preclinical and multiple Phase I clinical studies performed to date, GEN-1 has demonstrated good safety and impressive immune system stimulation and clinical activity. This trial will evaluate its value as an adjuvant to current standard of care in newly diagnosed Stage III/IV ovarian cancer patients with a relatively healthy immune system. We look forward to initiating the study in the first half of 2018."
The Phase I/II study builds on the highly promising clinical and translational research data for the recently completed Phase IB dose-escalating OVATION Study. This next Phase I/II study will have a dose escalating phase to 100 mg/m² to identify a safe and tolerable dose of GEN-1 while maximizing an immune response. The study protocol was unanimously supported by an expert medical advisory board and lead investigators from the Phase IB OVATION Study and is summarized below:

Open label, 1:1 randomized design

Enrollment up to 90 patients with Stage III/IV ovarian cancer patients at ten U.S. centers
Primary endpoint of improvement in progression-free survival (PFS) comparing GEN-1 with neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone.

PFS for patients treated per protocol in the Phase IB OVATION Study continues to be followed. Of the eight patients who received GEN-1 treatment over one year ago (cohort 1 – 3) and are being followed, only three patients’ cancer has progressed. This compares favorably to the historical median progression-free survival of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery. Of the remaining five patients who have been on the OVATION Study for over one year, their median PFS as of October 31, 2017 is 18.8 months with the longest progression-free patient at 24 months.

The protocol has been submitted to the FDA for its 30 day review and comment period. Pending this review, the Company expects to initiate enrollment of the Phase I portion of the study in the first half of 2018. The Company expects to have the study 50% enrolled by the end of 2018. Due to the open label design, clinical data will be disclosed throughout the execution of the trial as it is released by the study’s investigators.

"GEN-1 holds the potential of tremendous promise as a cancer treatment in the rapidly emerging area of immuno-oncology. Unlike the toxicities, poor tolerability, and poor pharmacokinetics of systemically administered recombinant IL-12, the beauty of GEN-1 is that it inspires secretion of highly-tolerable endogenous IL-12," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "Designed in consultation with leading thought leaders, this Phase I/II trial is expected to define an optimal dose, demonstrate GEN-1’s clinical benefit when compared with current standard of care, and provide insights on powering for a registration program as the candidate progresses through development."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer.

Cyclacel has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Cyclacel, 2017, NOV 13, 2017, View Source [SID1234521992]).

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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.