On November 09, 2015 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body’s immune system to fight cancer, reported results from multiple new preclinical studies demonstrating enhanced anti-tumor activity and immune activation for combinations of a preclinical bavituximab equivalent and checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 in preclinical models of breast cancer and melanoma (Press release, Peregrine Pharmaceuticals, NOV 9, 2015, View Source [SID:1234508140]). Additionally, the company announced preliminary results for a new clinical test specifically designed to illustrate how bavituximab, the company’s investigational phosphatidylserine (PS)-signaling pathway inhibitor, modulates immune responses in the tumor microenvironment. Results from these studies were presented at the 2015 annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), which was held in National Harbor, MD, on November 4 – 8, 2015.

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"The positive data presented at SITC (Free SITC Whitepaper) with regard to combinations of bavituximab and checkpoint inhibitors further support our belief that bavituximab has the potential to be a critical component of innovative combination cancer immunotherapies," said Jeff T. Hutchins, vice president preclinical development of Peregrine. "Particularly exciting is the new data in animal models of breast cancer which showed that a significantly greater number of subjects demonstrated anti-tumor activity when treated with the combination of bavituximab and anti-PD-1 as compared to treatment with anti-PD-1 alone. Additionally, combination treatment led to prolonged protection for animals as evidenced by their lack of new tumor development when later re-challenged with the same tumors."

Bavituximab is an investigational immunotherapy designed to assist the body’s immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine’s PS signaling pathway inhibitor candidates, including bavituximab, reverse the immunosuppressive environment that many tumors establish in order to proliferate, while also fighting cancer by activating immune cells that target and fight cancer. The preclinical equivalent of bavituximab, ch1N11, is used in animal model studies as a guide for clinical development.

Breast Cancer
Researchers from Duke University and Peregrine evaluated the combination of ch1N11 (preclinical bavituximab equivalent) and anti-PD-1 therapy versus anti-PD-1 stand-alone therapy in well-characterized murine breast cancers, including the triple negative breast cancer (TNBC) model E0771. Study data showed that the combination therapy significantly enhanced overall survival (p=0.0016) and was capable of mediating complete tumor regressions in a greater number of subjects compared to single agent treatments (60% vs. 20%). Data also demonstrated that animals receiving combination treatment had significant increases in tumor associated indicators of immune system activation, including CD45+, CD8+ and CD3+ T-cells. Importantly, the combination treatment led to a prolonged anti-tumor immune response which protected the animals against a re-challenge with the same tumor. This sustained anti-tumor response suggests the potential of the combination therapy to trigger immune system memory and support adaptive immune responses against reemerging disease in breast cancers. All study animals experienced no signs of adverse effects following repeated doses of all therapeutic agents.

Melanoma
In follow-on work, researchers from the University of Texas, Southwestern and Peregrine evaluated combinations of ch1N11 and checkpoint inhibitors (anti-PD-1 or anti-CTLA-4) versus each agent as a stand-alone therapy in common models of melanoma (B16F10 and K1735). Data showed that the combinations of ch1N11 with either anti-PD-1 or anti-CTLA-4 led to significantly greater levels of tumor infiltrating CD8+ T cells than any of the three agents alone. Additionally, findings demonstrated that the combination therapies were more effective at shifting the tumor microenvironment from immunosuppressive to immune active than the single agents, as shown by greater increases in the ratio of T effector cells to T regulatory cells, reactivation of tumor infiltrating T cells and restoration of the effector function of the tumor infiltrating T cells. This activity was more pronounced for the ch1N11/anti-PD-1 combination than for the ch1N11/anti-CTLA-4 combination. Based on these data, study investigators concluded that ch1N11 synergizes with checkpoint inhibitors to induce strong tumor specific CD8 T cell immunity.

"There is an extensive and growing collection of data that demonstrates that phosphatidylserine directly triggers broad immunosuppression in the tumor microenvironment and contributes to resistance to checkpoint inhibitor therapy. By targeting and blocking PS, bavituximab appears able to shift the tumor environment from immunosuppressive to immune active and, in turn, enhance the anti-tumor activity of checkpoint inhibitors such as anti-PD-1 and anti-CTLA4," said Bruce Freimark, Ph.D., director of pre-clinical oncology of Peregrine. "This latest data in well validated models of multiple tumor types further support our belief that bavituximab may be able to play an essential role in combination immuno-oncology treatment regimens. With this in mind, we are committed to evaluating the agent’s potential in combination with a range of cancer therapies against various cancer types."

ImmunoProfiling
Researchers presented preliminary results for a new custom assay designed to provide detailed profiles of immune activity in patient tumors. The Opal 6-plex quantitative immunofluorescence (IF) assay is specifically designed to measure the level and type of lymphocytes, myeloid and dendritic cell subsets found within the tumor microenvironment. This information is important as it can be used to correlate immune response parameters with bavituximab treatment outcome and patient survival.

Presented results demonstrated that the Opal assay could reliably detect, measure and phenotype lymphocytes and monocytes present in tumor tissues from rectal adenocarcinoma, hepatocellular carcinoma and advanced melanoma patients treated with bavituximab combination therapies. Importantly, the findings were able to show changes in key indicators of immune activation, including CD8+, CD4+ and regulatory T-cells, as well as myeloid and dendritic cells, in the tumor microenvironment following bavituximab treatment. The ability of this new assay to accurately measure specific immune responses is expected to provide important additional information to assist in Peregrine’s ongoing development efforts for bavituximab. This will be particularly valuable as the company works to better elucidate the connection between the drug candidate’s impact on immunomodulation and patient response to treatment.

"We are very pleased with the performance of the Opal assay, particularly its ability to compare the interaction of up to six phenotypic and functional markers on a single slide of tissue. The power and prognostic value of such immune activity assessments in the area of cancer was initially established by the Immunoscore, and we believe the Opal assay represents an important evolution of that work," said Bernard A. Fox, Ph.D., Harder Family Endowed Chair for Cancer Research, Member and Chief, Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center; a world-renowned translational cancer immunotherapist; a founding member of the Immunoscore steering committee. "I am looking forward to continued collaboration with Peregrine to further optimize and validate this assay to improve our understanding of immune infiltrate in tumors thereby facilitating the rational design and use of bavituximab in combination with novel and standard therapies."

About Bavituximab: A Targeted Investigational Immunotherapy
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine’s immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.

On November 09, 2015 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) reported clinical and preclinical data related to three of its clinical-stage programs at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, OncoMed, NOV 9, 2015, View Source [SID:1234508139]). Data from three posters covered Phase 1a safety, biomarker and anti-tumor activity of brontictuzumab (anti-Notch1, OMP-52M51), novel biomarker discoveries related to vantictumab (anti-Fzd7, OMP-18R5) in non-small cell lung cancer (NSCLC) and preclinical characterization of safety and efficacy for anti-DLL4/VEGF bispecific (OMP-305B83).

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Brontictuzumab Phase 1a: Single-agent Activity in Biomarker-positive Patients; Manageable Safety Profile

Among the data presented were Phase 1a clinical trial results for brontictuzumab in patients with advanced solid tumors. Brontictuzumab demonstrated single-agent activity in a biomarker-selected refractory patient population. Among 15 patients whose tumors overexpressed the activated form of Notch1, as measured by OncoMed’s proprietary immunohistochemistry (IHC) test, eight patients achieved stable disease or partial response for an overall clinical benefit rate of 53 percent. Anti-tumor activity was observed in adenoid cystic carcinoma, colorectal cancer and HER2 negative breast cancer. Partial responses were observed in two patients with adenoid cystic carcinoma after just one dose of brontictuzumab. Among patients whose tumors measured high in Notch1 activation, five have survived 100 days or longer as of the data cut off. There are five additional Notch1 high patients that are currently ongoing on the study and OncoMed plans to present follow-up data on those patients when the data matures. In biomarker negative subjects, only one of 11 had clinical benefit (9%). Brontictuzumab was generally well tolerated, with the most common adverse event being on-target, manageable diarrhea. Notch pathway and cancer stem cell pathway markers were reduced in serial tumor biopsies and in surrogate patient samples (blood) at doses above 1.5 mg/kg every three weeks. The single agent Phase 2 dose of brontictuzumab was established as 1.5mg/kg every three weeks.

"We are very encouraged by this early evidence of single-agent activity of brontictuzumab in a refractory biomarker-selected patient population. Notch1 has been shown to be elevated in a variety of solid tumor types, including breast, colorectal, esophageal, cholangiocarcinoma, pancreatic, small cell lung and adenoid cystic carcinomas," said Jakob Dupont, M.D., OncoMed’s Senior Vice President, Chief Medical Officer. "Based on these results and the manageable safety profile, Phase 1b combination studies of brontictuzumab in combination with chemotherapy are being contemplated with a particular emphasis on the Notch1 biomarker positive subjects."

These data were presented by Pamela Munster, M.D., Professor of Medicine, Program Leader Development Therapeutics, and Director of Early Phase Clinical Trials’ Program Helen Diller Cancer Center of the University of California, San Francisco in a poster titled: Safety and preliminary efficacy results of a first-in-human Phase I study of the novel cancer stem cell (CSC) targeting antibody brontictuzumab (OMP-52M51, anti-Notch1) administered intravenously to patients with certain advanced solid tumors (Abstract #C42).

"This successful Phase 1 study of brontictuzumab has provided much insight into this drug candidate. We have learned about the safety profile that can be managed; we have evidence of on-target effects against the Notch pathway; and we have observed single-agent activity in biomarker-selected patients," said Dr. Munster. "Taken together, data from this study suggests that brontictuzumab has the potential to benefit patients and should be developed in future studies with standard of care, particularly in biomarker selected patients."

Vantictumab in Non-Small Cell Lung Cancer — Novel Biomarker Identified

In a preclinical patient-derived xenograft non-small cell lung cancer (NSCLC) model, OncoMed researchers confirmed the anti-tumor activity of vantictumab both as a single-agent and in combination with taxane treatment. Sequential dosing (the administration of vantictumab two days prior to treatment with paclitaxel) was more efficacious than same-day dosing. Pharmacodynamic biomarkers showed that vantictumab inhibits genes in cancer stem cell pathways that support its mechanism of action. Importantly, LEF1, a key transcription factor in the Wnt pathway was identified as a potential predictive biomarker for treatment response in patient-derived xenograft models. LEF1 is being retrospectively evaluated as a predictive biomarker in OncoMed’s ongoing Phase 1b clinical trial of vantictumab in combination with docetaxel in patients with previously treated NSCLC. Results of these studies were presented on Friday, November 6 in a poster titled: Predictive and pharmacodynamic biomarkers of vantictumab (OMP-18R5; anti-Frizzled7) in non-small cell lung cancer (Abstract #A30) by Ann Kapoun, Ph.D. of OncoMed.

Anti-DLL4/VEGF Bispecific — Superior Inhibition of Tumor Growth

Preclinical studies of OncoMed’s dual-targeting anti-DLL4/VEGF bispecific antibody in xenograft tumor models demonstrated superior anti-tumor activity compared to either anti-DLL4 and anti-VEGF antibodies alone. The combination of anti-DLL4 and anti-VEGF resulted in broad-spectrum activity in many different tumor types including breast, colon, ovarian and pancreatic tumors. In serial transplantation studies, the anti-DLL4/VEGF bispecific antibody showed a greater effect than anti-DLL4 alone in delaying tumor recurrence following the termination of treatment and reducing the frequency of cancer stem cells in the tumors. Researchers also observed that simultaneous inhibition of DLL4 and VEGF induced a down-regulation of vasculature-related genes and decreased vasculature density. The anti-DLL4/VEGF bispecific antibody showed an improved cardiac profile in cynomolgus monkeys compared to anti-DLL4 which may translate to an improved safety profile in the clinic. OncoMed is currently testing the anti-DLL4/VEGF bispecific in a Phase 1a clinical trial for patients with advanced refractory solid tumors. These data were presented by Wang-Ching Yen, Ph.D., of OncoMed in a poster titled: Dual targeting of the DLL4 and VEGF pathways with a bispecific monoclonal antibody inhibits tumor growth and reduces cancer stem cell frequency (Abstract #C134) on November 8, 2015.

"The results of studies presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting provide valuable information on optimal dosing of vantictumab plus taxane therapy and have identified a promising biomarker in the non-small cell lung cancer indication," said John Lewicki, Ph.D., Executive Vice President, Chief Scientific Officer. "And, in preclinical models, our bispecific is demonstrating robust anti-tumor activity against a number of tumor types and the combination of anti-DLL4 and anti-VEGF appears to have the potential to improve upon the cardiotoxicity profiles of either agent alone. We look forward to evaluating how these data translate into the clinic in our ongoing trials."

Brontictuzumab, vantictumab and the anti-DLL4/VEGF bispecific are novel investigational therapeutics currently being evaluated in ongoing clinical trials. Patients interested in learning more about participating in one of OncoMed’s many clinical trials may learn more by calling 1-866-914-7347 or emailing [email protected].

On November 9, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, reported company highlights and financial results for the third quarter ended September 30, 2015 (Press release, Ignyta, NOV 9, 2015, View Source [SID:1234508136]).

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"Since the beginning of the third quarter of 2015, we have continued to make significant progress toward our objective of becoming a leading precision oncology biotechnology company that can provide patients with a variety of compelling cancer treatment options," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We continued to make strategic additions to our clinical pipeline that can help us eradicate residual disease in precisely defined patient populations through our acquisition from Lilly of exclusive worldwide rights to taladegib, a potent, orally bioavailable small molecule hedgehog/smoothened antagonist that has achieved compelling clinical proof of concept and a recommended Phase 2 dose in a Phase 1 dose escalation clinical trial. We also are grateful to Lilly for concurrently investing $30 million by acquiring 1.5 million shares of our common stock at $20 per share."

"In addition, we made strong progress executing development of our existing clinical-stage product candidates, including presenting promising Phase 1 data at leading conferences for entrectinib and RXDX-105, initiating our potentially registration-enabling STARTRK-2 Phase 2 clinical trial of entrectinib, and initiating our Phase 1/1b clinical trial of RXDX-107," continued Dr. Lim. "We expanded our team with incredibly talented people who, along with our existing team members, will help advance our multiple, complementary development programs for the benefit of cancer patients."

Company Highlights

Taladegib Exclusive License and Concurrent Stock Purchase by Lilly

In November 2015, Ignyta announced it had exclusively licensed from Eli Lilly and Company worldwide rights relating to Lilly’s taladegib oncology development program in exchange for an upfront payment of $2.0 million in cash and the issuance to Lilly of approximately 1.2 million shares of Ignyta’s common stock. Taladegib is a potent, orally bioavailable small molecule hedgehog/smoothened antagonist that has achieved compelling clinical proof of concept and a recommended Phase 2 dose in a Phase 1 dose escalation clinical trial. Ignyta also licensed exclusive worldwide rights to the topical formulation of taladegib, which is a late preclinical stage program being developed for the potential treatment of patients with superficial and nodular basal cell carcinoma.

Concurrently with the license, Ignyta entered into a stock purchase agreement with Lilly under which Lilly purchased a further 1.5 million shares of Ignyta common stock at a price of $20 per share in a private placement.

Presentation of RXDX-105 Clinical Data at ENA Conference

In November 2015, Ignyta announced interim results from the company’s ongoing Phase 1 clinical trial of RXDX-105, the company’s orally-available, small molecule multikinase inhibitor with potent activity against such key targets as RET and BRAF, which were presented at the 27th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts.

The dose escalation clinical trial was designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent RXDX-105 in patients with advanced or metastatic solid tumors that were not selected based on any molecular alteration.

As of the October 26, 2015, data cut-off for the presentation, the findings showed:

A total of 41 patients with a range of solid tumors were dosed in the clinical trial;
RXDX-105 was well tolerated to date:

The most frequent treatment-emergent adverse events were fatigue, vomiting, nausea, decreased appetite, constipation, diarrhea, hypertension and muscle spasms;

Three Grade 3 dose-limiting toxicities were observed: maculopapular rash, fatigue and diarrhea, each of which resolved upon study drug interruption;

There were no treatment-related serious adverse events. Two Grade 4 adverse events had occurred, consisting of intestinal obstruction and anemia, neither of which was considered to be treatment-related. No Grade 5 treatment-related adverse events or cumulative adverse events were observed;

The MTD and RP2D had not yet been determined;

Pharmacokinetic measurements showed increased exposure with increasing dose, with a half-life compatible with once-daily dosing. Dosing in the fed state appears to further increase exposure;

Exposure was reaching levels expected to be efficacious based on tumor growth inhibition in animal models of RET- and BRAF-driven tumors; and

Tumor regression was observed in six patients treated with 275 mg, including one confirmed partial response (40% reduction) in a patient with non-small cell lung cancer (NSCLC) with a KRAS G12C mutation. Two additional patients with thyroid cancer and squamous cell lung cancer exhibited reductions of 20% and 27%, respectively. In patients with tumor regression, there appears to be an exposure/response correlation.

Initiation of STARTRK-2 Phase 2 Clinical Trial of Entrectinib

In September 2015, Ignyta announced the initiation of its Phase 2 clinical trial of entrectinib, the company’s proprietary oral tyrosine kinase inhibitor targeting solid tumors that harbor activating alterations to NTRK1, NTRK2, NTRK3, ROS1 or ALK. This clinical trial is called STARTRK-2, the second of the "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases." The trial is a global, multicenter, open label, potentially registration-enabling Phase 2 clinical trial of entrectinib that utilizes a basket design with screening of patient tumor samples for gene rearrangements of the relevant targets. Such a basket design takes full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types that harbor a rearrangement of one of the genes encoding any one of entrectinib’s five protein targets.

Presentation of Updated Interim Entrectinib Clinical Trial Results at European Cancer Conference

In September 2015, the company announced updated interim results of its Phase 1 clinical trials of entrectinib, which were presented in an oral presentation session at the 2015 European Cancer Congress (ECC 2015) in Vienna, Austria.

The clinical trials included the ALKA-372-001 study and the STARTRK-1 study. Both trials were designed to determine the MTD and/or RP2D, as well as preliminary anti-cancer activity, of single agent entrectinib in patients with solid tumors with the relevant molecular alterations: NTRK1 (encoding TrkA), ROS1 or ALK for ALKA-372-001 and NTRK1/2/3 (encoding TrkA/B/C), ROS1 or ALK for STARTRK-1.

As of the August 15, 2015, data cut-off for the presentation, the findings showed:

A total of 92 patients with a range of solid tumors were dosed across both clinical trials, with nine patients treated at or above the RP2D beyond six months and one patient beyond one year.
Entrectinib was well tolerated:

Across both studies, the most frequent (>10% incidence) treatment-related adverse events were fatigue, dysgeusia, paresthesia, nausea, and myalgia. Seven of these were Grade 3 in severity, consisting of fatigue (4 patients), cognitive impairment (2 patients), and diarrhea (1 patient). No Grade 4 treatment-related adverse events were observed;

Across both studies, there were only three treatment-related serious adverse events: Grade 3 cognitive impairment and Grade 3 myocarditis, both of which occurred above the RP2D, and Grade 2 fatigue. All events were reversible and resolved upon dose modification;

The fixed daily dose RP2D was determined to be 600 mg, taken orally once per day (QD);

18 patients across both clinical trials met the company’s expected Phase 2 eligibility criteria, which include:
Presence of an NTRK1/2/3, ROS1 or ALK gene rearrangement, as opposed to other types of molecular alterations (e.g., SNPs, amplifications, deletions);

ALK-inhibitor and/or ROS1-inhibitor naïve; and

Treatment at or above the RP2D;

The response rate in the 18 patients who met these criteria across both studies was 72% (13 responses out of 18 treated patients, as assessed by the clinical sites). Nine of these responders remained on study treatment with durable responses of up to 21 treatment cycles. An additional 3 patients remained on study with stable disease. The responses included:

3 responses out of 4 patients with an NTRK1, NTRK2 or NTRK3 gene rearrangement, including patients with NSCLC, colorectal cancer and salivary gland cancer, with one of the responding patients remaining on treatment at 6 months; a fourth patient with an astrocytoma remained on treatment after two months with stable disease;

6 responses, including one complete response, out of 8 patients with a ROS1 gene rearrangement, all of which were in NSCLC. All of the patients who responded remained on treatment, the longest at 21 months; and

4 responses out of 6 patients with an ALK gene rearrangement, including two NSCLC patients and two patients with other solid tumors; two of the 4 responders had subsequently progressed.

Entrectinib had demonstrated objective tumor response in the central nervous system (CNS), a frequent site of metastases and progression of advanced solid tumors.

Issuance of Patent Covering Composition of Matter of RXDX-107

In October 2015, Ignyta announced that the U.S. Patent and Trademark Office issued U.S. Patent No. 9,150,517, entitled "Bendamustine Derivatives and Methods of Using Same." This patent contains claims that cover the composition of matter of Ignyta’s product candidate RXDX-107, and pharmaceutical compositions comprising RXDX-107. RXDX-107 is the company’s new chemical entity, next generation chemotherapeutic comprising an alkyl ester of bendamustine encapsulated in human serum albumin (HSA) to form nanoparticles. The patent has an expiration date of 2033, which does not include any potential patent term extension.

Initiation of Phase 1/1b Clinical Trial of RXDX-107

In September 2015, the company announced the initiation of its Phase 1/1b clinical trial of RXDX-107. This multicenter, open-label, dose-escalation clinical trial is designed to determine the MTD, RP2D, tolerability, pharmacokinetics and preliminary clinical activity of RXDX-107 in adult patients with locally advanced or metastatic solid tumors.

Enhancement of Leadership Capacity

In September 2015, Ignyta announced that Igor Bilinsky, Ph.D., was appointed to the newly-created role of General Manager, Immuno-Oncology and Senior Vice President, Special Operations, and that Valerie Harding, Ph.D., was appointed to the newly-created role of Senior Vice President, Chemistry, Manufacturing, and Controls.

Third Quarter 2015 Financial Results

For the third quarter of 2015, net loss was $14.6 million, or $0.49 per share, compared with $10.7 million, or $0.55 per share, for the third quarter of 2014.

Ignyta did not record any revenue for the three months ended September 30, 2015 or September 30, 2014.

Research and development expenses for the third quarter of 2015 were $10.4 million, compared with $8.6 million for the third quarter of 2014. The increase was primarily due to an increase in activities relating to development of entrectinib and the company’s other product candidates, including the assets acquired from Teva Pharmaceutical Industries Ltd. in March 2015. The increase between periods was also due to personnel expenses related to hiring and engaging additional employees and consultants to help advance the company’s product candidates and facilities-related expenses as a result of the expansion of the company’s leased facilities space.

General and administrative expenses were $3.9 million for the third quarter of 2015, compared with $2.2 million for third quarter of 2014. The increase was primarily caused by increases in personnel costs and investor relations, audit, legal and intellectual property costs.

At September 30, 2015, the company had cash, cash equivalents and available-for-sale securities totaling $163.1 million and current and long-term debt of approximately $31.0 million. At December 31, 2014, the company had cash, cash equivalents and available-for-sale securities totaling $76.6 million and current and long-term debt of approximately $21.0 million.

On November 9, 2015 Galectin Therapeutics Inc. (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, reported financial results for the three and nine months ended September 30, 2015 and provided a business update (Filing, 8-K, Galectin Therapeutics, NOV 9, 2015, View Source [SID:1234508135]). These results are included in the Company’s Quarterly Report on Form 10-Q, which has been filed with the U.S. Securities and Exchange Commission.

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Management commentary

"Galectin Therapeutics has never been in a better position advancing the development of our galectin-3 inhibitor in non-alcoholic steatohepatitis (NASH) and other therapeutic indications," said Jim C. Czirr, executive chairman of the company. "Our pipeline has progressed considerably during the third quarter and recent weeks, and we now have five clinical studies underway with our proprietary compound, GR-MD-02, in four different indications.

"We began a second Phase 2 study in NASH with advanced fibrosis, the NASH-FX study, during the quarter, and we continued to enroll patients in our Phase 2 study in NASH with cirrhosis, the NASH-CX study. We also began a pilot study to evaluate the potential efficacy of GR-MD-02 in patients with moderate-to-severe plaque psoriasis. More recently, after the close of the quarter we announced that the Providence Portland Medical Center submitted an Investigational New Drug (IND) application to study GR-MD-02 in combination with Keytruda in metastatic melanoma. This is in addition to its ongoing study of GR-MD-02 in combination with Yervoy in the same indication. To support this increased activity at Galectin, during the quarter we hired an industry veteran, Adam E. Allgood, Pharm.D., R.Ph. as executive director of clinical development," Mr. Czirr added.

Peter G. Traber, M.D., president, chief executive officer and chief medical officer, said, "NASH has been a topic of keen interest within the medical community as this disease appears to be overtaking hepatitis C as the number one cause of liver transplants, affecting up to 6 million people in the U.S. We are very excited about the potential of GR-MD-02 to treat the fibrosis and cirrhosis that can accompany NASH, and we are working hard to make efficacious treatment a reality.

"We are very pleased with the pace of our clinical studies and remain on track with our stated timelines," added Dr. Traber. "The NASH-CX trial, which if successful has potential to be a component of a pivotal study, began enrolling patients with NASH cirrhosis, with 156 patients in total to be enrolled. Patients are being evaluated with either 8 mg/kg of GR-MD-02, 2 mg/kg of GR-MD-02 or placebo, and are being randomized 1:1:1. The primary endpoint for this trial is change in hepatic venous pressure gradient (HVPG) compared with placebo, with secondary endpoints of fibrosis stage on biopsy as well as the percent of collagen on biopsy at one year of treatment. Additionally, the HVPG and liver biopsy measurements will be correlated with non-invasive measurements of liver fibrosis and function using FibroScan and 13C-methacetin breath test, respectively. We expect top-line data readout by the end of 2017.

Dr. Traber continued, "The NASH-FX trial in 30 patients with NASH with advanced fibrosis, but not cirrhosis, is proceeding as planned. This four-month treatment trial will evaluate the efficacy of 8 mg/kg of GR-MD-02 versus placebo, using non-invasive endpoints. LiverMultiScan, a multi-parametric nuclear magnetic resonance imaging method developed by Perspectum Diagnostics, will be used to measure the change in inflammation and fibrosis as a primary endpoint. The secondary goal is to compare the primary endpoint of LiverMultiScan with two secondary endpoints that are non-invasive measures of liver stiffness that correlate with fibrosis, magnetic resonance elastography and FibroScan. We expect data readout from the NASH-FX trial in the third quarter of 2016.

"We have also begun screening patients with moderate-to-severe plaque psoriasis in a proof-of-concept, open-label Phase 2a trial. In this trial 10 patients will be treated with 8mg/kg of GR-MD-02 every 2 weeks over 90 days. Research has shown that galectin-3 is increased in the skin of psoriasis patients, thus we have good support for the mechanism of action of our compound. In addition, as previously disclosed, one subject in our Phase 1 NASH study had an apparent remission of psoriasis. As such, we believe it is worthwhile to explore this indication further in this small study.

"We expect that the Portland Cancer Center will begin enrolling patients in its Phase 1b study of GR-MD-02 in combination with Keytruda within the coming weeks, following the filing of its IND in October. Keytruda is an immune checkpoint inhibitor indicated for patients whose melanoma had progressed after treatment with Yervoy or targeted therapy in melanomas that have a BRAF mutation. Preclinical data show that GR-MD-02 holds potential to increase the effectiveness of other therapies and represents a promising approach to enhance cancer immunotherapy. GR-MD-02 is also the subject of an ongoing study in combination with Yervoy being conducted by same investigators at the Portland Cancer Center. We are very pleased to be supplying our compound to the investigators," Dr. Traber concluded.

Additional information about the Company’s clinical development program and clinical trials is available on the CEO Perspectives website at View Source

Financial Results
For the three months ended September 30, 2015, the Company reported a net loss applicable to common stockholders of $6.2 million, or ($0.26) per share, compared with a net loss applicable to common stockholders of $3.9 million, or ($0.17) per share, for three months ended September 30, 2014. The increase in net loss applicable to common stockholders is largely due to higher research and development expenses related to the Company’s Phase 2 clinical program.
Research and development expense for the three months ended September 30, 2015 was $4.5 million, compared with $2.0 million for three months ended September 30, 2014. The increase is primarily due to increased costs related to the Company’s Phase 2 clinical program.

General and administrative expense for the three months ended September 30, 2015 was $1.4 million, compared with $1.5 million for the three months ended September 30, 2014. The primary reason for the decrease was related to a decrease in stock-based compensation expense in the three months ended September 30, 2015, compared with 2014.

For the nine months ended September 30, 2015, the Company reported a net loss applicable to common stockholders of $16.2 million, or ($0.69) per share, compared with a net loss applicable to common stockholders of $13.0 million, or ($0.60) per share, for the nine months ended September 30, 2014. The increase in net loss applicable to common stockholders is largely due to higher research and development expenses related to the Company’s Phase 2 clinical program.

Research and development expense for the nine months ended September 30, 2015 was $10.2 million, compared with $6.3 million in the prior year’s period. The higher research and development expense is related to increased expenses associated with the Company’s Phase 2 clinical studies.

General and administrative expense for the nine months ended September 30, 2015 was $5.2 million, compared with $5.4 million for the nine months ended September 30, 2014. The decline was due to lower stock-based compensation expense.
As of September 30, 2015, the Company had $21.3 million of non-restricted cash and cash equivalents available to fund future operations. The Company believes that its cash on hand as of September 30, 2015 is sufficient to fund currently planned operations and research and development activities through September 30, 2016.

On November 09, 2015 ArQule, Inc. (Nasdaq:ARQL) reported the results of preclinical and clinical studies focusing on tivantinib, ARQ 087, ARQ 092, and ARQ 751 (Press release, ArQule, NOV 9, 2015, View Source [SID:1234508132]). The data were presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting on November 7th, 2015. The poster presentations can be accessed in the "Investor and Media" section of our website, www.arqule.com, under "Recent Data Presentations."

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For the first time, data from an exploratory sub-analysis of the MARQUEE trial with tivantinib in non-small cell lung cancer in patients with advanced disease and epidermal growth factor receptor (EGFR) mutations were presented. The data showed tivantinib, when added to erlotinib, increased progression-free survival to 13 months compared to 7.5 months in the erlotinib plus placebo arm. The sub-analysis included 109 patients of which 56 were in the combination tivantinib plus erlotinib arm of the trial. The data were highlighted in an AACR (Free AACR Whitepaper) press release and press conference.

"The data from the sub-analysis of the MARQUEE trial supports our focus on precision medicine," said Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "Although the study did not meet its primary endpoint, this analysis is encouraging and offers evidence that tivantinib when dosed in a specific patient population can provide substantial benefit."

Additionally, the company presented pre-clinical and clinical data on its early stage proprietary pipeline that support ArQule’s efforts to address the needs of patients in therapeutic areas of high unmet need through precision medicine. Data presented on FGFR inhibitor, ARQ 087, demonstrate that FGFR2 dysregulation correlates with efficacy and supports the on-going phase 2 trial in intrahepatic cholangiocarcinoma. Similarly, data presented on AKT inhibitors, ARQ 092 and ARQ 751, demonstrate that both drugs inhibit AKT and provide strong rationale for further studies in patients harboring AKT1 and PI3K mutations.

"Data presented at this year’s AACR (Free AACR Whitepaper)-NCI-EORTC conference are part of ArQule’s translational effort to connect preclinical and clinical research and guide a true precision medicine endeavor," said Giovanni Abbadessa, Vice President of Clinical Development, Translational Medicine and Medical Affairs at ArQule. "Both ARQ 092 and ARQ 087 have shown single-agent activity in vitro, in vivo and in patients in cancers driven by genetic alterations of their respective targets, AKT and FGFR. In addition, these pre-clinical data find confirmation in the clinical results achieved by ARQ 087 and ARQ 092 in their respective phase 1 clinical trials in genetically-altered endometrial and breast cancer and in FGFR2-driven cholangiocarcinoma, respectively. Combinability data reported for both experimental drugs with standard therapies may allow even more development options for the future."

Precision Medicine

Tivantinib is enrolling in two biomarker-driven phase 3 trials, METIV-HCC and JET-HCC. ARQ 087 is enrolling in a biomarker-driven phase 2 trial in intrahepatic cholangiocarcinoma (iCCA) with FGFR translocations. ARQ 092 is enrolling in a phase 1b biomarker-driven trial in patients with AKT and PI3K activating mutations including patients with breast, endometrial and ovarian cancers.

About MET and tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in Phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in a number of tumors. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.

About the AKT Pathway, ARQ 092 and ARQ 751

ARQ 092 and ARQ 751 are orally available, selective small molecule inhibitors of the AKT kinase. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.

ARQ 092, the lead compound in ArQule’s AKT program, has completed Phase 1a clinical testing and has advanced into Phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphoma and tumors harboring either AKT or PI3K mutations. A number of next-generation compounds in the Company’s AKT program are in early to late stages of pre-clinical development. The company plans to file an Investigational New Drug (IND) application by the end of 2015 for ARQ 751, a next generation AKT inhibitor.

About FGFR and ARQ 087

ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor ("FGFR") family with demonstrated efficacy in FGFR2 amplified tumors. The FGFR pathway is disrupted in several ways in human cancer, thus providing numerous therapeutic targets for an inhibitor of this pathway. ARQ 087 has demonstrated inhibition of tumor growth and downstream signaling in vivo in tumors whose growth is driven by these targets.

Signals of single agent activity with this compound were observed in Phase 1a testing. Phase 1b expansion cohorts with ARQ 087 include patients with cholangiocarcinoma and adrenocortical tumors, as well as those with FGFR translocations, amplification and mutations. Clinical development of ARQ 087 has advanced into Phase 2 for intrahepatic cholangiocarcinoma ("iCCA") following the observation of two confirmed partial responses in this patient population in the Phase 1 portion of the program.