Chugai Files a New Drug Application for a ROS1/TRK Inhibitor Entrectinib for the Treatment of ROS1 Fusion-Positive Non-Small Cell Lung Cancer

On March 15, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed a new drug application to the Ministry of Health, Labour and Welfare (MHLW) for a ROS1/TRK inhibitor entrectinib for the treatment of ROS1 fusion-positive non-small cell lung cancer (NSCLC) (Press release, Chugai, MAR 15, 2019, View Source [SID1234534393]).

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"With the previous filing of NTRK fusion-positive solid tumors, which is a rare type of cancer, and ROS1 fusion-positive NSCLC, which accounts for one to two percent of NSCLC, Chugai wishes that entrectinib would become a new treatment option for these patients and we will continue working to contribute to the development of personalized medicine," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit.

This application for approval is based on an integrated analysis of an open-label, multicenter, global phase II study (the STARTRK-2 study) and three overseas phase I studies (the STARTRK-NG study, the STARTRK-1 study and the ALKA-372-001 study). Efficacy was evaluated in 53 patients with ROS1 fusion-positive NSCLC while safety assessment was conducted with 355 patients registered in the four trials.

As the top pharmaceutical company in the field of oncology in Japan, Chugai will work to obtain early approval in order to provide entrectinib as a new treatment option for patients and medical professionals.

[Reference information]

Media release issued by Roche on February 19, 2019
Title: FDA grants Priority Review to Roche’s personalised medicine entrectinib
View Source
Media release issued by Chugai on December 19, 2018
Title: Chugai Files a New Drug Application for a ROS1/TRK Inhibitor Entrectinib for the Treatment of NTRK Fusion-Positive Solid Tumors
View Source
Media release issued by Roche on September 24, 2018
Title: Roche’s investigational medicine entrectinib showed a durable response of more than two years in people with a specific type of lung cancer
View Source
About entrectinib
Entrectinib is an oral medicine in filling for approval for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 or ROS1 gene fusions. It is a selective, CNS-active tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and inhibit proliferation of cancer cells with ROS1 or NTRK gene fusions. FDA has granted priority review for entrectinib for the treatment of NTRK fusion-positive solid tumors and ROS1 fusion-positive NSCLC.

About ROS1 fusion-positive NSCLC
ROS1 fusion gene is an abnormal gene that can be formed by fusing the ROS1 gene and other genes (CD74, etc.) as a result of chromosomal translocation for some reason. The ROS1 fusion kinase made from ROS1 fusion gene is thought to promote cancer cell proliferation. ROS1 fusion gene is found in about one to two percent of non-small cell lung cancer, among which it is more expressed in adenocarcinoma.

Sutro Biopharma Initiates Phase I Clinical Trial of STRO-002 for the Treatment of Ovarian and Endometrial Cancers

On March 15, 2019 Sutro Biopharma, Inc. (NASDAQ: STRO) reported that it has dosed the first patient in a Phase I study of STRO-002, an anti-folate receptor alpha (FoIRα) antibody-drug conjugate (ADC), in patients with ovarian and endometrial cancers (Press release, Sutro Biopharma, MAR 15, 2019, View Source [SID1234534392]). This is the second product candidate to be evaluated in clinical trials resulting from Sutro’s XpressCF+ technology platform.

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The study is a multi-center, open-label, dose-escalation with dose expansion Phase I trial evaluating the safety, tolerability and preliminary anti-tumor activity of STRO-002. The study plans to enroll up to 160 women with advanced relapsed and/or progressive ovarian, fallopian, primary peritoneal or endometrial cancer.

"Moving our second product candidate into human clinical trials is another momentous milestone in Sutro’s evolution from a technology platform company to a clinical stage company," said Sutro CEO Bill Newell. "Our goal is to ultimately help fill the unmet need for more targeted therapies for patients with ovarian and endometrial cancer and advancing STRO-002 into the clinic brings us one step closer to achieving this."

STRO-002 is designed to target FoIRα, a cell-surface protein highly expressed in ovarian cancer. In preclinical studies, STRO-002 demonstrated potent in vitro cytotoxicity in ovarian cancer cell lines and significantly inhibited tumor growth in multiple ovarian cancer xenograft models. In safety studies conducted in non-human primates, STRO-002 was well tolerated at clinically relevant doses. "Based on observations from pre-clinical studies, STRO-002 has the potential to overcome traditional dose-limiting factors in the clinical setting, including ocular toxicity, which is a vexing problem with some ADCs," said Sutro Chief Medical Officer, Arturo Molina, M.D.

Denise Uyar, M.D., Associate Professor of Gynecology Oncology at Medical College of Wisconsin, an investigator in the STRO-002 study added, "Sutro’s unique ADC has the potential to be another important therapeutic option for oncologists in treating patients with ovarian and endometrial cancer. We look forward to evaluating the next-generation of ADCs in this study."

The Phase I study will consist of two parts: dose-escalation followed by dose-expansion. In both parts of the study, STRO-002 will be dosed as an intravenous infusion on Day 1 of 21-day cycles. Additional information can be found at View Source

STRO-002 was developed using Sutro’s proprietary cell-free protein synthesis and site-specific conjugation platforms, which facilitates precision design and rapid empirical optimization of ADCs and other product candidates.

Actinium Pharmaceuticals to Present at the Oppenheimer & Co. 29th Annual Healthcare Conference

On March 15, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) ("Actinium" or "the Company") reported that it will present a corporate overview at the Oppenheimer & Co. 29th Annual Healthcare Conference, being held March 19-20 at the Westin Grand Central Hotel in New York City (Press release, Actinium Pharmaceuticals, MAR 15, 2019, View Source [SID1234534391]).

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Presentation Details:

Date:

Wednesday, March 20

Time:

1:35 pm Eastern Time

Room:

Consulate

Venue:

Westin Grand Central Hotel

212 East 42nd St, New York City

(PRNewsfoto/Actinium Pharmaceuticals, Inc.)

Management will be conducting 1-on-1 meetings with conference attendees. Meetings with Actinium can be scheduled by emailing Steve O’Loughlin, Principal Financial Officer: [email protected].

MorphoSys AG Annual Report 2018

On March 15, 2019 MorphoSys AG presented the corporate presentation (Press release, MorphoSys, MAR 15, 2019, View Source [SID1234534390]).

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ProMIS Neurosciences Announces Fiscal Year 2018 Annual Results

On March 15, 2019 ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, reported its operational and financial results for the year ended December 31, 2018. Unless specified otherwise, all amounts are in Canadian dollars (Press release, ProMIS Neurosciences, MAR 15, 2019, View Source [SID1234534377]).

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"Over the course of the past year, the value of our unique discovery and development platform was further evidenced as ProMIS made considerable progress in expanding its portfolio of opportunities across multiple neurodegenerative diseases", stated Eugene Williams, ProMIS’ Executive Chairman.

"PMN310, our lead antibody therapeutic candidate for Alzheimer’s disease, showed further significant positive differentiation in both potential efficacy and safety compared to competitive antibody therapeutics currently in development. In addition, antibody candidates selectively targeting toxic forms of alpha-synuclein for Parkinson’s disease and toxic, aggregated forms of TDP43 for amyotrophic lateral sclerosis (ALS) were identified and further characterized to support initiation of pharmaceutical partnering discussions."

Corporate Highlights

During 2018, we completed private placements providing aggregate gross proceeds of approximately $7,240,000.
In the course of 2018, we received proceeds from the exercise of warrants and stock options in the amount of $1,797,640.
Alzheimer’s disease (AD) program
In January 2018, our lead product candidate for Alzheimer’s disease, PMN310, showed potential for an improved safety profile and improved therapeutic potency in head-to-head comparisons to other amyloid beta- directed antibodies.
In August 2018, we announced further evidence supporting potential for an improved safety profile in direct comparison to other amyloid beta-directed antibodies in clinical development. PMN310 showed no binding to amyloid beta (Aβ) plaque in AD brain samples in contrast to BAN2401 (Biogen/Eisai) and aducanumab, which both displayed robust Aβ plaque reactivity. Binding of therapeutic antibodies to Aβ deposits in brain tissue, in particular blood vessels, is believed to underlie the development of ARIA-E (amyloid-related imaging abnormalities with edema) or brain swelling in treated AD patients.
In June 2018, we announced the initiation of producer cell line development for PMN310, the first major step in the manufacturing process for therapeutic antibodies.
In October 2018, we announced identification of novel targets on misfolded, pathological forms of tau. The development of antibody therapeutics that selectively block these toxic forms of tau constitutes an exciting approach to treating AD and other neurodegenerative diseases.
Parkinson’s disease (PD) and ALS programs
In June 2018, we announced several antibody candidates selectively targeting the aggregated, toxic forms of alpha-synuclein, implicated in the development and progression of PD, as well as TDP43 (TAR DNA binding protein), implicated in the development of ALS.
In October 2018, the neuroprotective effect of our antibodies was evaluated on rat primary dopaminergic neurons injured by exposure to toxic oligomers of alpha-synuclein, an in vitro model of PD. In the test, several of our antibodies, selectively targeting toxic forms of alpha-synuclein, significantly blocked the death of neurons induced by these toxic forms.
People
In March 2018, Sharon Cohen, M.D., was appointed to our Scientific Advisory Board. Dr. Cohen is Medical Director and Principal Investigator of the Toronto Memory Program, an independent medical facility for dementia care and research. Her memory clinic and dementia clinical trials program are the largest and most active in Canada and have contributed substantially to patient care and to global clinical trial cohorts.
In September 2018, James Kupiec, M.D., was appointed Chief Medical Officer. Dr. Kupiec is a physician-scientist with over two decades of broad, hands-on experience in translational, early- and late-stage neuroscience drug development in the pharmaceutical industry.
In December 2018, Rudolph Tanzi, Ph.D., was appointed to our Scientific Advisory Board. Dr. Tanzi is a renowned neuroscientist and geneticist with scientific expertise in Alzheimer’s disease and brain health. He serves as Vice-chair of Neurology, Director of the Genetics and Aging Research Unit, and as a Director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital. He is also the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School.
In January 2019, we completed a private placement providing aggregate gross proceeds of approximately $2,198,800.
Financial Results

Annual Results of Operations

The Company’s net loss for the year ended December 31, 2018 was $10,167,050, compared to a net loss of $6,019,970 for the year ended December 31, 2017. Included in the net loss for the year ended December 31, 2018 were non-cash expenses of $1,081,600, representing share-based compensation and amortization of an intangible asset, compared to $700,953 for the year ended December 31, 2017. The increase in the net loss for the year ended December 31, 2018 is mainly related to the costs associated with developing the Company’s AD therapeutics program, increased contracted resources and associated costs, supporting its patent portfolio, associated general corporate expenditures and higher share-based compensation.

Research and development expenses for the year ended December 31, 2018 were $7,409,546, as compared to $3,704,010 in the year ended December 31, 2017. The increase in research and development expense for the year ended December 31, 2018 is primarily attributed to higher research program costs for the AD therapeutics program, increased contracted resources, share-based compensation, recruiting and travel expense.

General and administrative expenses for the year ended December 31, 2018 were $2,757,979, as compared to $2,318,752 in the year ended December 31, 2017. The increased expenditures for 2018 is primarily attributable to increased investor relations/public relations, salaries and associated costs and other professional fees, offset by foreign exchange gain on U.S. dollar denominated expenses decreased legal expense and share-based compensation.

Outlook

As a prelude to the first PMN310 clinical trial in AD, ProMIS anticipates using a novel biomarker approach that may show evidence of slowing of neuronal death early in the development program. To accomplish this, we plan to initiate a natural history evaluation of biomarker changes in untreated, early AD patients.

We anticipate potential initial results of the first clinical trial with PMN310 in late 2020.

The Company will also continue to further characterize the potential benefits of its programs selectively targeting toxic aggregates of TDP43 in ALS and toxic forms of alpha-synuclein in PD to further support on-going pharmaceutical partnering discussions.