On March 27, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), has received SAKIGAKE Designation for the treatment of HER2-positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW) (Press release, Daiichi Sankyo, MAR 27, 2018, View Source [SID1234525386]).

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"There are no HER2-targeting treatment options currently available for patients with HER2-positive gastric cancer whose tumors are no longer controlled by trastuzumab," said Koichi Akahane, PhD, MBA, Executive Officer, Head of Oncology Function, R&D Division, Daiichi Sankyo. "We look forward to working closely with the Japan Ministry of Health, Labour and Welfare under the terms of the SAKIGAKE program to accelerate the development of DS-8201 particularly since Japan has one of the highest incidence rates of gastric cancer worldwide."

The SAKIGAKE Designation System promotes R&D in Japan, driving early practical application for innovative pharmaceutical products, medical devices and regenerative medicines. As a designated medicine under the SAKIGAKE Designation system, DS-8201 will have prioritized consultation, a dedicated review system to support the development and review process, as well as reduced review time from the normal 12 to 6 months.

"We are pleased that DS-8201 has received SAKIGAKE Designation for advanced HER2-positive gastric cancer, which follows the Breakthrough Therapy and Fast Track designations granted by the U.S. FDA for HER2-positive metastatic breast cancer," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "These three designations for DS-8201 underscore our commitment to active and close collaborations with health authorities in order to potentially bring DS-8201 as a new treatment option to patients with different types of HER2-expressing cancers worldwide as quickly as possible."

SAKIGAKE Designation was granted based on the results of an ongoing phase 1 study assessing the safety, tolerability and preliminary efficacy of DS-8201. Updated preliminary results of DS-8201 from a subgroup analysis of HER2-positive advanced gastric cancer previously treated with trastuzumab and chemotherapy were recently presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.1

Unmet Need in Gastric Cancer
Gastric cancer is the fifth most common cancer worldwide, with nearly one million new cases reported in 2012.2 Approximately half of all gastric cancer cases occur in eastern Asia, with Japan having the third highest incidence rate worldwide.2,3 Gastric cancer is the third leading cause of cancer-related death worldwide, and the second leading cause of cancer-related death in Japan.2,4

Approximately one in five gastric cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells.5 HER2-expressing gastric cancer is an area of unmet medical need as advances in the treatment of the disease have been limited, largely due to its genetic complexity and heterogeneity.6 Currently, there are no approved HER2-targeting therapy options for patients with HER2-positive advanced gastric cancer after treatment with trastuzumab.

About DS-8201
DS-8201 is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in pivotal phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01), pivotal phase 2 development for HER2-positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01), phase 2 development in advanced colorectal cancer and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science Franchise, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: DS-8201, an antibody drug conjugate (ADC) for HER2-expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/
refractory acute myeloid leukemia (AML) with FLT3-ITD mutations; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com

On March 27, 2018 Public University Corporation Nagoya City University (Chairman: Kenjiro Kohri; Nagoya, Aiichi Prefecture; hereinafter, "Nagoya City University"), Chubu University, Incorporated Educational Institution Chubu University (President: Osamu Ishihara; Kasugai, Aichi Prefecture; hereinafter, "Chubu University"), Daiichi Sankyo Company, Limited (Representative Director, President and COO: Sunao Manabe; head office: Chuo-ku, Tokyo; hereinafter, "Daiichi Sankyo") and Mitsubishi UFJ Capital Co., Ltd. (President: Muneki Handa; head office: Chuo-ku, Tokyo; hereinafter "Mitsubishi UFJ Capital") reported that they will commence open innovation research ("the research") on a new cancer hyperthermia therapy*1 (Press release, Daiichi Sankyo, MAR 27, 2018, View Source [SID1234525387]).

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Based on results of joint research under TaNeDS*2, an open competition joint discovery research grant program operated by Daiichi Sankyo, the research aims to find and optimize magnetic nanoparticles with high capacity for delivery into tumors, and then study their practical application as a new hyperthermia therapy for cancer treatment by researching an alternating magnetic field generating device for efficiently heating the particles.

To carry out the research, a new company called OiDE RYO-UN, Inc. (head office: Chuo-ku, Tokyo; hereinafter "RYO-UN") has been established and will be wholly funded by the OiDE Fund Investment Limited Partnership ("OiDE Fund") operated by Mitsubishi UFJ Capital.

If the pre-agreed goals of the three-year joint research are achieved, Daiichi Sankyo will purchase all of the stock of RYO-UN in order to continue research and development for the project on its own. Then, at the time of achieving its own goals and after a successful product launch, Daiichi Sankyo will pay considerations to Nagoya City University and Chubu University in the form of royalties.

The research on a new cancer hyperthermia treatment is the third OiDE Fund*3 investment, and Daiichi Sankyo and Mitsubishi UFJ Capital plan to continue to carry out open innovation projects to develop new drug discovery platforms using the OiDE Fund.

*1 New cancer hyperthermia therapy
Cancer hyperthermia therapy makes use of the characteristic that cancer cells have weaker heat resistance than normal cells. This therapy selectively kills cancer cells through heating and there are expectations that it can be combined with radiotherapy, chemotherapy and cancer immunotherapy. The new cancer hyperthermia therapy aims to achieve high safety and efficacy by specifically heating cancer cells at a constant temperature.

*2 TaNeDS
TaNeDS (Take a New Challenge for Drug diScovery) is a collaborative drug discovery initiative being pursued by Daiichi Sankyo in open innovation. This is an open competition joint discovery research grant program whose scope covers research from the exploratory stage to the pre-practical application stage.

*3 OiDE (Open innovation for the Development of Emerging technologies) Fund
A fund jointly established by Mitsubishi UFJ Capital and Daiichi Sankyo in 2013, and operated by Mitsubishi UFJ Capital

On March 27, 2018 i2020 Accelerator reported that Stelvio Therapeutics has joined its early drug discovery ecosystem (Press release, Stelvio Therapeutics, MAR 27, 2018, View Source [SID1234555715]). i2020 aims to accelerate research programs with differentiated biology and established development paradigms towards advanced leads and clinical candidates. The i2020 Accelerator deploys a world-wide network of well-established R&D resources, financial and BD&L capabilities to help Stelvio Therapeutics advance its proprietary epigenetic platform for glioblastoma therapies.

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i2020 received a startup funding commitment of $30 million from the specialty life science investor, Torrey Pines Investment. "With the risk of taking on projects at early development stages being very significant, i2020 has to be reasonably selective with the programs it supports," comments Nikolay Savchuk, Managing Director at Torrey Pines. "Stelvio Therapeutics’ AI-driven epigenetic signature-based platform, which identifies compounds that trigger differentiation of cancer stem cells into benign cell types, matches i2020’s target profile well. It is a first-in-class project with strong clinical hypothesis, a well-defined product profile and clear development milestones."

"i2020 aligns well with our overall goals, since it provides a robust network of relevant R&D, business strategy and scientific resources, together with an agile business model and flexible partnering options," comments Attila Hajdu, CEO at Stelvio Therapeutics. "This exciting partnership is a tremendous step towards our shared mission of delivering innovative medicines of value to the patients that need them. With our combined technology and resources, the traditional approaches of chemo and radiotherapy would be toppled and we could see a cure for glioblastoma within our lifetime."

(Filing, Annual, Compugen, 2017, MAR 27, 2018, View Source [SID1234525031])

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On March 27, 2018 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported financial results for the three months and year ended December 31, 2017 and reported on corporate developments (Press release, Aptose Biosciences, MAR 27, 2018, View Source;p=RssLanding&cat=news&id=2340004 [SID1234525006]). Unless specified otherwise, all amounts are in US Dollars.

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The net loss for the quarter ended December 31, 2017 was $3.28 million ($0.12 per share) compared with $2.97 million ($0.23 per share) for the quarter ended December 31, 2016. Total cash and cash equivalents and investments as of December 31, 2017 were $11.4 million, or $13.3 million Canadian dollars, which, based on current operations and estimations, provide the Company with sufficient resources to fund research and development and operations into Q1 2019.

"2017 was a year of tremendous progress for Aptose," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We achieved our strategic goal in bringing CG’806, our oral first-in-class pan-FLT3/pan-BTK inhibitor, from an early preclinical molecule to a stage where we are preparing to file an IND and initiate clinical trials in patients with acute myeloid leukemia (AML) and certain B-cell malignancies later this year. This required considerable scale-up manufacturing and formulation development, as well as pathway suppression analysis, xenograft efficacy, and pharmacokinetic and safety studies. Separately, we successfully completed formal root cause studies for APTO-253, our small molecule c-Myc inhibitor, as well as the manufacture of a new cGMP batch of drug supply sufficient for dosing AML patients in an ongoing Phase Ib trial. We look forward to completing the required stability and other studies with the new clinical supply to submit to the FDA, with the hope of having the CMC-related clinical hold released for a timely re-initiation of patient dosing. At the same time, we and our collaborators continued to perform mechanistic research on ‘806 and ‘253 and have generated data that compel us to advance both compounds clinically."

Corporate Highlights

Orphan drug designation and patent allowance granted for CG’806 – During the year, the USPTO issued a patent that claims numerous compounds including the CG’806 compound, pharmaceutical compositions comprising the CG’806 compound, and methods of treating various diseases. Furthermore, in December the FDA granted orphan drug designation to CG’806 for the treatment of patients with AML. The FDA assigns orphan drug designation to support the development of medicines for underserved patient populations. Orphan drug designation provides Aptose certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

ASH presentations – In December, Aptose and its collaborators, The University of Texas MD Anderson Cancer Center and the OHSU Knight Cancer Institute, delivered multiple poster presentations and abstracts at the American Society of Hematology (ASH) (Free ASH Whitepaper) 59th Annual Meeting & Exposition. Researchers at MD Anderson elucidated the unique ability of CG’806 to kill a broad range of AML cells by suppressing multiple pathways, to overcome resistance seen with other FLT3 inhibitors, and to act synergistically with other agents. OHSU researchers evaluated the activity of CG’806 on patient primary bone marrow specimens through the Beat AML Initiative. CG’806 exhibited broad and potent single agent activity, and enhanced activity when combined with Bcl-2 or BET inhibitors, against AML and CLL patient samples. In addition, two abstracts on APTO-253, one describing its molecular target leading to suppression of c-MYC gene expression and the other describing its synthetic lethality comparable to olaparib in cells deficient in BRCA1 and BRCA2 function, were published online by ASH (Free ASH Whitepaper). Results demonstrate that, unlike olaparib, APTO-253 does not produce myelosuppression even at the maximum tolerated dose.

Completed manufacture of APTO-253 cGMP clinical supply – Aptose has completed manufacture of the cGMP clinical supply that will be required for the potential return of APTO-253 to the clinic. Stability, sterility, mock infusion, animal bridging and blood compatibility studies are currently underway. Upon successful completion of those studies, Aptose plans to submit findings to the FDA to seek release of the CMC-related clinical hold and allow resumption of patient dosing in the open Phase 1b trial in patients with AML or myelodysplastic syndrome (MDS).

CG’806 pre-IND progress – Aptose successfully manufactured CG‘806 drug substance and formulated drug product, and then performed animal dose range finding preclinical studies of CG’806 in rodents and dogs, and successfully dosed up to 1000 mg/kg/day, the maximum feasible dose, with no observable toxicities noted. Also, Aptose completed manufacturing 2.6kg of a drug batch that will be used for IND-enabling GLP animal toxicity studies.

Global license agreement with OHM Oncology – Earlier this month, Aptose announced an exclusive global license agreement that provides OHM Oncology with the rights for the development, manufacture and commercialization of APL-581, as well as related molecules from Aptose’s dual bromodomain and extra-terminal domain motif (BET) protein and kinase inhibitor program. Aptose will retain reacquisition rights to certain molecules, while OHM will have the rights to develop and sublicense all other molecules.
Financial Results

Effective December 31, 2017, we changed our presentation currency to US dollars from Canadian dollars. All amounts included in this document are in US dollars unless disclosed otherwise. The change in reporting currency was accounted for on a retrospective basis as if the US dollar had always been the Company’s presentation currency. Accordingly, the financial statements for all the periods presented have been translated to the US dollar.

The decrease in the net loss during the year ended December 31, 2017 compared with the year ended December 31, 2016 results mostly from our decision in January 2017 to refocus our resources on our CG’806 development program and towards determining the root cause of the manufacturing issue with the APTO-253 program. Expenses were lower due to the cancellation of the LALS/Moffitt collaboration, lower costs associated with the APTO-253 program, and offset by increased development activities related to the CG’806 development program which were nominal in comparable periods, other than the license fee that was paid in June 2016 to acquire an option on the technology.

Research and Development
Components of research and development expenses

In the 2016 comparative period, we paid $1.0 million to CrystalGenomics, Inc. ("CG") for an option fee related to the CG’806 technology and in that period began research and development activities for this program;
An increase in research and development activities related to our CG’806 development program. Activities in the current year ended December 31, 2017 included formulation studies and PK studies and the manufacturing of a first batch of the drug substance to be used in dose range finding studies, the initiation of the dose range finding studies, and the initiation of the manufacturing of a GLP batch of drug substance to be used in the toxicity studies. CG’806 program expenses were nominal in the comparative period as the technology was licensed to us in June 2016;
Reduced expenditures on the APTO-253 program. In the year ended December 31, 2017, we completed the root cause analysis and determined the cause of the manufacturing issue, established a Corrective and Prevention Action plan to ensure the clinical supply can be manufactured in a reliable manner, and the initiation of manufacturing of a new clinical supply. In the comparative period, we were actively manufacturing a clinical batch and preparing to return APTO-253 to the clinic; and
Savings from cancellation of the LALS/Moffitt collaboration which was active in the year ended December 31, 2016. There are no costs related to this program in the year ended December 31, 2017.
General and Administrative
Components of general and administrative expenses

General and administrative expenses excluding salaries, decreased slightly in the year ended December 31, 2017, compared with the year ended December 31, 2016. The decrease is mostly the result of lower travel costs, consulting and rent costs in the first six months of the fiscal year related to cost containment initiatives taken in the prior fiscal year and offset by higher investor relations, professional fees and travel costs in the three months ended December 31, 2017;
Salary expenses in the year ended December 31, 2017, were slightly lower in comparison with year ended December 31, 2016. Savings from reduced headcount were partially offset by higher bonuses recognized in the current period; and
Stock-based compensation decreased in the year ended December 31, 2017, compared with the year ended December 31, 2016, due to large forfeitures in the three months ended March 31, 2017 and also due to grants in the prior periods having a greater fair value than the grants issued in the year ended December 31, 2017, and therefore contributing to higher stock-based compensation in the year ended December 31, 2016.
FOURTH QUARTER RESULTS OF OPERATIONS

The changes in research and development expenses in the three months ended December 31, 2017 as compared to the three months ended December 31, 2016 result from the following:

An increase in R&D activities on our CG’806 program as described above;
A decrease in R&D activities on our APTO-253 program as described above;
Savings from cancellation of the LALS/Moffitt collaboration as described above; and
Higher salaries expense mostly related to additional clinical research staff hired at the end of the year to prepare for returning APTO-253 to the clinic.

higher investor relations, professional fees and travel costs in the three months ended December 31, 2017;
higher salaries related mostly to a bonus adjustment in the comparative period; and
stock option grants issued in the current year with a lower grant date fair value than the comparative period.
Conference Call and Webcast

Aptose will host a conference call today, Tuesday, March 27, 2017 at 5:00 p.m. EDT to discuss results for the three months and year ended December 31, 2017. Participants can access the conference call by dialing (844) 882-7834 (North American toll-free number) and (574) 990-9707 (International) and using conference ID # 8873259. The conference call can be accessed here and will also be available through a link on the Investor Relations section of Aptose’s website at ir.aptose.com. An archived version of the webcast along with a transcript will be available on the Company’s website for 30 days. An audio replay of the webcast will be available approximately two hours after the conclusion of the call through April 3, 2018 by dialing (855) 859-2056, using the conference ID # 8873259.