On April 27, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported a comprehensive program update on entrectinib – an investigational, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor TRK, ROS1 or ALK fusions – currently being studied in a registration-enabling Phase 2 clinical trial known as STARTRK-2 (Press release, Ignyta, APR 27, 2017, View Source [SID1234518716]).

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"Today’s update is the result of our team’s diligent efforts to advance entrectinib through the clinic for the benefit of patients with TRK and ROS1 fusion-positive cancers," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We are proud to announce substantial progress towards dual entrectinib NDA submissions for both TRK and ROS1, and are excited by the opportunity to serve two distinct groups of patients with cancer."

Entrectinib development highlights:

TRK –

Based on written feedback from FDA, Ignyta intends to pursue an NDA submission for entrectinib to support a TRK fusion-positive, tissue agnostic indication.
Ignyta’s entrectinib program is more than 85% enrolled to goal for the primary efficacy analysis for a TRK tissue agnostic NDA submission, and is on track to complete enrollment by the 3rd quarter of 2017.
Within STARTRK-2, several dozens of patients with TRK fusions have been enrolled, across more than 15 different tumor types; and investigators in approximately a dozen different countries on four continents currently have experience treating patients with entrectinib.
Ignyta plans to announce top-line NDA registration-enabling data from STARTRK-2, after consultation with FDA, in the first half of 2018.
ROS1 –

Ignyta is simultaneously pursuing an NDA submission for entrectinib to support a ROS1 fusion-positive NSCLC indication.
More than 50 ROS1 fusion-positive NSCLC patients have been enrolled to support a potential ROS1 NSCLC NDA for entrectinib, greater than the number that formed the basis of crizotinib’s approval in this setting.
Ignyta reported interim data from 32 patients with ROS1 fusion-positive NSCLC, including new patients from STARTRK-2 who were enrolled as of December 16, 2016.
24 out of the 32 patients had confirmed RECIST responses, for an objective response rate (ORR) of 75%.
The median duration of response (DOR) was 17.2 months among the responder patients, and the median progression free survival (PFS) was 19.1 months among all patients.
11 out of the 32 patients, or 34%, had CNS metastases at baseline.
Of these 11 patients with CNS disease, 7 had confirmed RECIST responses, for an ORR of 64% in ROS1 NSCLC patients with CNS metastases.
When aggregated with Ignyta’s Phase 1 data set of patients with primary and secondary CNS disease, a total of 10 out of 16 patients had confirmed RECIST responses, for an ORR of 63% in TRK, ROS1 or ALK patients with CNS disease.
Entrectinib commercial highlights:

Based upon analysis of more than 120,000 cancer patient samples from internal and external sources, Ignyta believes that in the US each year there are approximately 1,000-2,000 new patients with TRK fusion-positive advanced solid tumors, and 2,000 new patients with ROS1 fusion-positive NSCLC.
Entrectinib is simultaneously tracking towards TRK tissue agnostic NDA and ROS1 NSCLC NDA submissions in 2018, with anticipated US launch in 2019.
Based upon these dual indications, Ignyta believes the total addressable market for entrectinib could be in excess of $1B annually in the US alone.
A conference call and webcast is being held on April 27, 2017 at 4:30 p.m. Eastern/1:30 p.m. Pacific to discuss the entrectinib program update. To participate in the conference call, please dial (877) 548-7906 (U.S.) or (719) 325-4765 (International) and provide Conference ID 2028635. To access the live webcast, go to View Source." target="_blank" title="View Source." rel="nofollow">View Source

A replay of the presentation will be available shortly after the conclusion of the live call in the Investors section of the company’s website at View Source, and will be archived and available at that site for 14 days.

On April 27, 2017 Cytokinetics, Inc. (Nasdaq:CYTK) reported total revenues for the first quarter of 2017 were $4.2 million, compared to $8.4 million, during the same period in 2016 (Press release, Cytokinetics, APR 27, 2017, View Source [SID1234518715]). Net loss for the first quarter was $25.9 million, or $0.62 per basic and diluted share, respectively. This is compared to a net loss for the same period in 2016 of $12.5 million, or $0.31 per basic and diluted share. As of March 31, 2017, cash, cash equivalents and investments totaled $257.2 million.

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"In the first quarter of 2017, we advanced our novel muscle biology-directed programs through important late-stage clinical trial milestones. In particular, the last patients enrolled in VITALITY-ALS moved through their primary efficacy endpoint visits towards the conclusion of the Phase 3 trial and we look forward to results expected later this year," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "We also made key progress with Astellas in the expansion of our clinical trials programs for CK-2127107, opening enrollment for Cohort 2 in our ongoing Phase 2 trial in adolescent and adult patients living with spinal muscular atrophy, and preparing to start additional trials in patients with ALS and elderly subjects with limited mobility."

Recent Highlights and Upcoming Milestones

Skeletal Muscle Program

tirasemtiv

Convened the third Data Monitoring Committee Meeting for VITALITY-ALS (Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices after Treatment for a Year in ALS); the Committee recommended the continuation of VITALITY-ALS without modification.

Continued conduct of VITALITY-ALS and enrollment in VIGOR-ALS (Ventilatory Investigations in Global Open-Label Research in ALS), an open-label extension clinical trial designed to assess the long-term safety and tolerability of tirasemtiv, in patients with ALS who have completed participation in VITALITY-ALS.

Announced the advancement of our research collaboration with Origent Data Sciences to prospectively validate Origent’s computer model designed to predict the course of disease progression using baseline data from VITALITY-ALS. The model is expected to be completed prior to analyzing results of VITALITY-ALS.

Conducted clinical, regulatory, non-clinical and other planning activities intended to support potential regulatory filings and registration of tirasemtiv in North America and Europe.

Engaged Health Technology Assessment organizations to understand payor interests and to inform market access activities in ALS.

Expect to continue to enroll patients who complete VITALITY-ALS into VIGOR-ALS throughout 2017.

Expect results from VITALITY-ALS in Q4 2017.
CK-2127107

Announced pre-clinical data for CK-2127107 showing that this next-generation fast skeletal troponin activator (FSTA) improves muscle function in mouse models of spinal muscular atrophy (SMA). The results were presented at the MDA Scientific Conference in Arlington, VA.

Completed enrollment of Cohort 1 in the Phase 2 clinical trial of CK-2127107 in patients with SMA, conducted by Cytokinetics in collaboration with Astellas; announced that Cohort 2 opened enrollment.

Expect data from the Phase 2 clinical trial of CK-2127107 in patients with SMA in 2H 2017.

Expect Astellas to continue enrollment in a Phase 2 clinical trial of CK-2127107 in patients with COPD in 2017.

Expect Astellas to begin a Phase 1b clinical trial of CK-2127107 in elderly patients with limited mobility in Q2 2017.

Expect to begin a Phase 2 clinical trial of CK-2127107 in patients with ALS in mid-2017.
Cardiac Muscle Program

omecamtiv mecarbil

Announced additional results from COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure), a Phase 2 trial evaluating omecamtiv mecarbil in patients with chronic heart failure, showing that omecamtiv mecarbil improved measures of left ventricular myocardial deformation, a marker of myocardial function that has been related to outcomes. These results further support the direct effect of omecamtiv mecarbil to improve myocardial contractile function. The results were presented in a Poster Session at the American College of Cardiology’s 66th Annual Scientific Session (ACC.17) in Washington, D.C.

Continued to activate sites and enroll patients in GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil which is being conducted by Amgen, in collaboration with Cytokinetics.

Expect data from a Phase 2 clinical trial of omecamtiv mecarbil in Japanese patients with chronic heart failure in Q3 2017.

Expect continued enrollment of patients with chronic heart failure in GALACTIC-HF throughout 2017.
Pre-Clinical Research

Continued research activities under our joint research program with Amgen directed to the discovery of next-generation cardiac muscle activators and under our joint research program with Astellas directed to the discovery of next-generation skeletal muscle activators. In addition, company scientists continued independent research activities directed to our other muscle biology programs.
Corporate

Agreed to sell to Royalty Pharma a 4.5% royalty on potential worldwide sales of omecamtiv mecarbil for $90 million and $10 million of Cytokinetics common stock.

Agreed to exercise an option under our collaboration agreement with Amgen to co-invest $40 million in the Phase 3 development program of omecamtiv mecarbil. As a result, Cytokinetics is eligible to receive an incremental royalty of up to 4% on increasing worldwide sales of omecamtiv mecarbil outside of Japan. Exercising our option and co-funding affords Cytokinetics the right to co-promote omecamtiv mecarbil in institutional care settings in North America, with reimbursement by Amgen for certain sales force activities.

Joined the global initiative with the European Organisation for Rare Diseases (EURORDIS) and the National Organization for Rare Disorders (NORD) to raise awareness of Rare Disease Day, an international campaign dedicated to elevating the public understanding of rare diseases.
Financials

Revenues for the first quarter of 2017 were $4.2 million, compared to $8.4 million during the same period in 2016. Revenues for the first quarter of 2017 included $2.7 million of research and development revenues and $1.4 million of license revenues from our collaboration with Astellas, $0.9 million in research and development revenues from our collaboration with Amgen, and $0.3 million in research and development revenues from our collaboration with The ALS Association. Revenues from our collaboration with Amgen were offset by a payment of $1.3 million to Amgen related to the option to co-fund the Phase 3 development program of omecamtiv mecarbil in exchange for an increased royalty upon potential commercialization. Revenues for the same period in 2016 were comprised of $4.0 million of license revenues and $3.7 million of research and development revenues from our collaboration with Astellas, and $0.6 million of research and development revenues from our collaboration with Amgen.

Total research and development (R&D) expenses for the first quarter of 2017 were $19.3 million, compared to $13.5 million for the same period in 2016. The $5.8 million increase in R&D expenses for the first quarter of 2017, compared with the same period in 2016, was primarily due to an increase of $2.5 million in outsourced clinical costs mainly associated with VITALITY-ALS, our ongoing Phase 3 trial of tirasemtiv, $1.4 million in outsourced research and pre-clinical costs mainly associated with clinical manufacturing activities, $1.3 million in personnel related expenses due to increased headcount costs, and $0.2 million in laboratory expenses.

Total general and administrative (G&A) expenses for the first quarter of 2017 were $8.1 million compared to $6.8 million for the same period in 2016. The $1.3 million increases in G&A expenses for the first quarter of 2017, compared to the same period in 2016, was primarily due to an increase of $0.7 million in personnel-related expenses due to increased headcount and non-cash stock compensation expense and $0.8 million in outsourced costs primarily related to commercial development, partially offset by a decrease in corporate legal fees of $0.5 million.

On April 27, 2017 Cellectar Biosciences, Inc. (Nasdaq: CLRB), (the "company"), an oncology-focused, clinical stage biotechnology company, reported preclinical data that demonstrate the utility of the company’s lead compound, CLR 131, and CLR 125 for use in solid tumors, as well as the potential benefits of a multi-dose treatment (Press release, Cellectar Biosciences, APR 27, 2017, View Source [SID1234518714]).

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The company conducted two studies assessing a single dose and two doses with either CLR 131 or CLR 125. In the first study, mice receiving two doses of CLR 131 50uCi (day 0 and day 42) experienced mean survival of 135.6 days versus 64.6 days for mice receiving a single dose of CLR 131 50uCi in a Capan-1 xenograft model of human pancreatic adenocarcinoma. The second dose provided double the survival benefit in this challenging disease model and it is possible that additional doses could further enhance these outcomes.

The second study assessed one versus two doses of CLR 125 in a PC3 prostate cancer xenograft model. Mice receiving two doses of approximately 500uCi (day 0 and day 28) achieved survival of 161 days compared to 135 days for mice receiving a single dose of approximately 500uCi. Importantly, the mice receiving two doses had nearly double the initial disease burden (as measured by tumor volume) than the mice in the control arm of the study, which experienced 122 days of survival.

The data from both of these solid tumor animal studies indicate that multiple doses of a radiotherapeutic phospholipid-ether drug conjugate (PDC) resulted in an increased survival benefit over a single dose. The pancreatic cancer model demonstrates the potential utility of CLR 131 in solid tumors. Additionally, the prostate cancer model, combined with prior research by other laboratories, suggests that increased disease burden may impact the efficacy of a single, fixed dose of a radiotherapeutic, and that additional survival benefit could be obtained via a multi-dose treatment.

"These experiments further validate the potential utility of our PDC platform, specifically CLR 131, in the treatment of both solid and hematologic cancers," said Jim Caruso, president and CEO of Cellectar Biosciences. "We are intrigued by the enhanced survival benefit seen with an additional dose in these studies and look forward to further exploring the effect of multiple doses in patients suffering from relapse and refractory hematologic malignancies in our ongoing Phase II clinical study."

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated as a single-dose treatment in a Phase I clinical trial in patients with relapsed or refractory (R/R) multiple myeloma as well as in a Phase II clinical trial for R/R MM and select R/R lymphomas with either a one- or two-dose treatment. Based upon preclinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall survival, an improvement in progression-free survival, surrogate efficacy marker response rate, and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131, directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in more than 80 different xenograft models of cancer.

On April 27, 2017 Pfizer Inc. reported that its investigational next-generation ALK/ROS1 tyrosine kinase inhibitor, lorlatinib, was granted Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), previously treated with one or more ALK inhibitors (Press release, Pfizer, APR 27, 2017, View Source [SID1234518709]).

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Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy designation is intended to expedite the development and review of a potential new medicine if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.1 The Breakthrough Therapy designation is distinct from the FDA’s other mechanisms to expedite drug development and review.2 ALK gene rearrangement is a genetic alteration that drives the development of lung cancer in some patients. 3,4 Due to additional mutations that the tumor may acquire during treatment, disease progression remains a challenge in patients with ALK-positive metastatic NSCLC.5

"This regulatory designation recognizes the potential for lorlatinib to provide an important treatment option for patients with ALK-positive NSCLC whose cancers have progressed despite treatment. Pfizer’s rapid development of lorlatinib reflects a commitment to developing biomarker-driven therapies to meet the evolving needs of patients," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "We look forward to working with the FDA to accelerate the development of this therapy."

The Breakthrough Therapy designation is supported by the efficacy and safety data of an ongoing Phase 1/2 clinical trial of lorlatinib, which includes patients with ALK-positive NSCLC who were previously treated with one or more ALK inhibitors.

Additionally, the Phase 3 CROWN study (NCT03052608) recently began enrolling patients. CROWN is an ongoing, open label, randomized, two-arm study comparing lorlatinib to crizotinib in the first-line treatment of patients with metastatic ALK-positive NSCLC. Please visit clinicaltrials.gov for more information on this study.

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is the leading cause of cancer death in both men and women.6 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.7 Approximately 57 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease where the five-year survival rate is only 5 percent. 8 NSCLC can be further categorized into distinct subsets that are classified by a number of factors, including histology and the molecular makeup of the tumor. Epidemiology studies suggest that approximately 3 to 5 percent of NSCLC tumors are ALK-positive.9

About Lorlatinib

Lorlatinib is an investigational next-generation ALK/ROS1 tyrosine kinase inhibitor that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of both ALK and ROS1. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. Lorlatinib is an investigational agent and has not received regulatory approval for any indication anywhere in the world.

On April 27, 2017 DelMar Pharmaceuticals (Nasdaq: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that it will present a poster at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) held in Chicago, IL from June 2nd to June 6th, 2017 (Press release, DelMar Pharmaceuticals, APR 27, 2017, View Source [SID1234518707]).

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The following poster will be presented during the Central Nervous System Tumors Session:

Date and Time:
June 5th at 1:15 PM – 4:45 PM central daylight time
Abstract Title:
Clinical Trials of VAL-083 in Patients With Chemo-Resistant
Glioblastoma.
Abstract ID:
TPS2082
About VAL-083

VAL-083 is a "first-in-class," small-molecule DNA-targeting agent that demonstrated clinical activity against a range of cancers including GBM in historical clinical trials sponsored by the U.S. National Cancer Institutes (NCI). DelMar has demonstrated that VAL-083’s anti-tumor activity against GBM is unaffected by the expression of MGMT in vitro. High expression of MGMT in MGMT-unmethylated GBM patients is correlated with chemo-resistance and poor survival following treatment with temozolomide, the current standard-of-care. Further details can be found at View Source

VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer. Based on historic clinical trials run by NCI, the modern phase I/II dose finding trial run by DelMar in GBM (ASCO 2016), and recent guidance from the FDA, the Company is embarking on multiple phase 2 and 3 clinical trials for VAL-083 encompassing both front-line and recurrent GBM therapy.

DelMar has announced plans to advance VAL-083 into a pivotal randomized multi-center Phase 3 clinical trial for the treatment of bevacizumab-failed GBM. DelMar has also initiated a Phase 2 trial for bevacizumab-naïve recurrent MGMT-unmethylated GBM patients in collaboration with the MD Anderson Cancer Center. A separate international Phase 2 trial for newly diagnosed MGMT-unmethylated GBM will be initiated at Sun-Yat Sen University in Guangzhou China. DelMar believes that data from its clinical trials, if successful, will form the basis of a new treatment paradigm for the vast majority of GBM patients whose tumors exhibit features that make them unlikely to respond to currently available therapies. The poster at ASCO (Free ASCO Whitepaper) 2017 will highlight the clinical results to date and the Company’s clinical trial designs for VAL-083 in GBM.

About Glioblastoma Multiforme (GBM)

GBM is the most common and aggressive primary brain cancer. Current standard of care includes surgery, radiation and treatment with temozolomide (TMZ), however nearly all tumors recur and the prognosis for recurrent GBM is dismal. Most GBM tumors have unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT); a validated biomarker for TMZ-resistance. Second-line treatment with anti-angiogenic agent bevacizumab has not improved overall survival (OS) and 5-year survival is less than 3%. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent targeting N7-Guanine and inducing interstrand DNA cross-links, double-strand breaks and cell death in GBM cell lines and GBM cancer stem cells, independent of MGMT status in vitro. VAL-083 readily crosses the blood-brain barrier and accumulates in brain tumor tissue. Our recent phase I/II clinical trial in recurrent GBM patients failing both TMZ and bevacizumab suggested that VAL-083 offers clinically meaningful survival benefits for patients with recurrent GBM and pinpointed a new dosing regimen (40 mg/m2/d on days 1, 2, and 3 of a 21-day cycle) which was well-tolerated and was selected for study in subsequent GBM trials. DelMar has initiated, or plans to initiate, three additional GBM trials, the results of which may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM. These trials include:

i)
An ongoing single-arm, biomarker driven, Phase 2 study to determine if VAL-083 treatment of MGMT-unmethylated adult GBM patients at first recurrence/progression, prior to bevacizumab improves overall survival at 9 months, compared to historical control with lomustine (clinicaltrials.gov identifier: NCT02717962).
ii)
A planned pivotal Phase 3 study in recurrent GBM after failing both TMZ and bevacizumab. The control arm will consist of a limited number of salvage chemotherapies currently used in bevacizumab-failed GBM. If successful, this study will serve as the basis for a New Drug Application (NDA) submission for VAL-083.
iii)
A planned single arm, biomarker driven, Phase 2 study to confirm the tolerability and efficacy of VAL-083 in combination with radiotherapy in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT levels. (clinicaltrials.gov identifier: NCT03050736).