On January 13, 2019 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biotechnology company specializing in the development of novel treatments for brain tumors, reported it has entered into a licensing agreement with The University of Texas MD Anderson Cancer Center (Press release, CNS Pharmaceuticals, JAN 13, 2020, View Source [SID1234553603]). The agreement grants Company the right to develop and commercialize WP1244, a new class of DNA-binding agent designed to cross the blood-brain barrier for the potential treatment of primary and metastatic brain cancers.

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This agreement allows for the continued development of WP1244, which has been shown to have high anti-tumor activity in preclinical studies. WP1244 was designed using a "modular" strategy, which combines intercalation and groove-binding modes into molecules with the requisite chirality and binding-site size to impart meaningful selectivity. Previous pre-clinical tests have demonstrated the agent’s ability to cross the blood-barrier in animal models with no acute clinically observable toxicity.

"Our licensing agreement has allowed CNS to double its portfolio with the addition of WP1244. We are extremely excited to continue the development of this entirely new class of DNA-binding agent," stated CEO of CNS, John M. Climaco. "We believe the compound demonstrates enormous potential through its novel mechanism of action, ability to cross the blood-brain barrier, and tremendous potency, 500 times that of classic DNA binding agents such as daunorubicin. WP1244 has shown to be mechanistically and biologically novel and selective, and its addition to our pipeline furthers our goal of being the leading developer of organ-targeted cancer therapeutics."

About WP1244

WP1244 is a novel DNA binding agent with relatively high molecular weight (981.3 MW) having a polyamide moiety attached to the amino sugar. WP1244 is exceedingly potent having in vitro IC50 values in the subnanomolar range and is currently being studied for its therapeutic potential in preclinical studies. A previous 5-mouse pilot study performed with WP1244 confirmed the presence of WP1244 in murine brain tissue. WP1244 was designed utilizing a "modular" design strategy, which combines intercalation and groove-binding modes into molecules with the requisite chirality and binding-site size to impart meaningful selectivity. Pre-clinical studies of WP1244 have demonstrated its potential ability to cross the blood-brain barrier in animal models. WP1244 was developed at The University of Texas MD Anderson Cancer Center.

On January 13, 2020, Coherus BioSciences, Inc. (the "Company") reported that it has entered into a license agreement (the "License Agreement") with Innovent Biologics (Suzhou) Co., Ltd. ("Innovent") for the development and commercialization of a biosimilar version of bevacizumab (Avastin) in any dosage form and presentations ("bevacizumab Licensed Product") in the United States and Canada (the "Territory") (Filing, 8-K, Coherus Biosciences, JAN 13, 2020, View Source [SID1234553226]). Under the License Agreement, Innovent granted to the Company an exclusive, royalty-bearing license to develop and commercialize the bevacizumab Licensed Product in the field of treatment, prevention or amelioration of any human diseases and conditions as included in the label of Avastin. Under the License Agreement, the Company also acquired an option to develop and commercialize Innovent’s biosimilar version of rituximab (Rituxan) in any dosage form and presentations (the "rituximab Licensed Product" and together with the bevacizumab Licensed Product, the "Licensed Products") in the Territory. Subject to the terms of the License Agreement, the Company may exercise its option within 12 months of its receipt of certain regulatory materials from Innovent. Following the Company’s option exercise, Innovent’s biosimilar version of rituximab would be deemed a Licensed Product for all purposes of the License Agreement and Innovent would grant to the Company an exclusive, royalty-bearing license to develop and commercialize Innovent’s biosimilar version of rituximab in the field of treatment, prevention or amelioration of any human diseases and conditions as included in the label of Rituxan.

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Innovent will supply the Licensed Products to the Company in accordance with a manufacturing and supply agreement to be executed by the parties. Under the License Agreement, the Company acquired the right to require Innovent to perform technology transfer for the manufacturing of the Licensed Products in the Territory and, upon completion of such technology transfer, the Company will have the exclusive right to manufacture the Licensed Products in the Territory.

The Company will pay Innovent an upfront payment of $5,000,000. Additionally, the Company is obligated to pay Innovent an aggregate of up to $40,000,000 in milestone payments in connection with the achievement of certain development, regulatory and sales milestones with respect to the bevacizumab Licensed Product and, if the Company’s option is exercised, an aggregate of up to $40,000,000 in milestone payments in connection with the achievement of certain development, regulatory and sales milestones with respect to the rituximab Licensed Product. The Company will share a percentage of net sales of Licensed Products with Innovent in the mid-teens to low twenty percent range. If the Company exercises its option, it would be required to pay an option exercise fee of $5,000,000. Subject to the terms of the License Agreement, if the Company requests Innovent to perform technology transfer for the manufacturing of the Licensed Products, it would be required to pay up to $10,000,000 for fees related thereto.

For the bevacizumab Licensed Product, the License Agreement’s initial term continues in effect for ten years after the effective date of the License Agreement, and thereafter renews for successive two year periods upon mutual agreement by the parties, unless otherwise terminated in accordance with its terms. For the rituximab Licensed Product, the License Agreement’s initial term would continue in effect for ten years after the effective date of the option effective date and thereafter would renew for successive two year periods upon mutual agreement by the parties, unless otherwise terminated in accordance with its terms. Either party may terminate the License Agreement for the other party’s material breach that is not cured within a specified time period or for the other party’s bankruptcy or insolvency-related events. Innovent may terminate the License Agreement if the Company undergoes a change of control with a competitor of Innovent and does not assign the License Agreement to a third party within a certain period of time. On a Licensed Product-by-Licensed Product basis, the Company may terminate the License Agreement based on certain market conditions beginning 12 months after the first commercial sale of such Licensed Product with 18 months advance written notice. Also on a Licensed Product-by-Licensed Product basis, the Company may terminate the License Agreement in certain circumstances of delays, or anticipated delays, in the achievement of regulatory approval of such Licensed Product in the United States, if the Company receives certain adverse regulatory feedback from the U.S. Food and Drug Administration ("FDA") for such Licensed Product, or if the Company receives written FDA meeting minutes indicating that the FDA recommends an additional phase 3 clinical trial efficacy comparability study to support the regulatory approval of such Licensed Product in the United States.

On January 13, 2020 TIO Bioventures, an emerging life science venture creation fund with a mission to build companies with innovative anti-cancer therapies, reported the launch of Treadwell Therapeutics, a clinical-stage oncology company exploiting cancer cells’ vulnerabilities to develop first-in-class and best-in-class small molecules to address unmet needs in patients with cancer (Press release, Tio Bioventures, JAN 13, 2020, View Source [SID1234553221]). Treadwell, one of TIO Bioventures family of companies launched from its discovery engine, TIO Discovery, was established with an initial $27 million in seed financing from TIO Bioventures to develop a robust pipeline of novel, first-in-class, small molecule drug candidates.

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"At Treadwell, we are developing small molecules designed to leverage world-class, innovative science in cancer biology and immune-oncology with pan-cancer potential, including hematological malignancies from the TIO Discovery development engine," said Dr. Michael Tusche, Treadwell Co-Chief Executive Officer and Partner at TIO Bioventures.

The origins of Treadwell lie in cutting-edge research incubated at the Campbell Family Institute for Breast Cancer Research (CFIBCR) within the University Health Network (UHN), Canada’s largest research hospital. Based on this research, Treadwell scientists have designed and advanced from discovery to Phase 2 clinical development, a first-in-class PLK4 kinase inhibitor, CFI-400945 and a potentially best-in-class TTK inhibitor, CFI-402257. These candidates have demonstrated encouraging safety and efficacy profiles in multiple investigator-sponsored clinical trials. In addition, Treadwell is poised to bring a third molecule into the clinic in early 2020. This agent, CFI-402411, an oral immunomodulatory kinase inhibitor with activity toward HPK1, an untapped immune-oncology target. Preclinical studies have demonstrated the promise of CFI-402411 as a potential monotherapy and in combination with existing checkpoint inhibitors across both solid and hematological cancers. Treadwell’s product candidates are wholly-owned and have been developed in TIO Discovery, a unique R&D engine wholly owned by TIO.

Leadership

The Company announced the appointment of Rachel W. Humphrey, M.D., as Head of R&D at TIO Discovery as well as Chief Medical Officer and Board Member at Treadwell. Dr. Humphrey joins TIO Bioventures and Treadwell with over two decades of experience as a senior clinical leader in oncology drug development for both large pharmaceutical and emerging biotechnology companies. Her experience includes overall leadership of the clinical development of Yervoy (ipilmumab), the first FDA approved checkpoint inhibitor, at Bristol-Myers Squibb, the development of Imfinzi (durvalumab) at Astra Zeneca and the development of Nexavar (sorafenib) at Bayer, as primary driver of the vision, science and direction during critical periods in the development for these transformational medicines.

"TIO Bioventures novel approach to found, launch, and support companies such as Treadwell speaks to this powerful and successful relationship of world-class scientists with deeply experienced management executives, and I am delighted to join Treadwell at such a pivotal time in the Company’s growth," said Dr. Humphrey. "I look forward to working with the team to further drive the development of these candidates with encouraging anti-cancer activity and exciting novel targets."

She will join Treadwell Therapeutics’ existing leadership team composed of world-class experts in immunology and oncology drug development, including Dr. Tak Mak, co-founder and managing partner of TIO Bioventures, who has led the development of multiple successful biotechnology companies.

On Januaruy 13, 2020 Ontario Institute for Cancer Research (OICR) and the University Health Network (UHN) have discovered detailed new information about the subtypes of pancreatic cancer (Press release, OICR, JAN 13, 2020, View Source [SID1234553214]). A better understanding of the disease groups may lead to new treatment options and improved clinical outcomes for this lethal disease.

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The study, published today in Nature Genetics, represents the most comprehensive analysis of the molecular subtypes of pancreatic cancer to date. Through detailed genomic and transcriptomic analyses, the research group identified five distinct subtypes of the disease (Basal-like-A, Basal-like-B, Classical-A, Classical-B, and Hybrid) with unique molecular properties that could be targeted with novel chemotherapies, biologics and immunotherapies.

"Therapy development for pancreatic cancer has been hindered by an incomplete knowledge of the molecular subtypes of this deadly disease," says lead author Dr. Faiyaz Notta, Co-Leader of OICR’s Pancreatic Cancer Translational Research Initiative (PanCuRx) and Scientist at UHN’s Princess Margaret Cancer Centre. "By rigorously analyzing advanced pancreatic cancers – which is the stage of disease that most patients have when they’re diagnosed – we were able to create a framework. This will help us develop better predictive models of disease progression that can assist in personalizing treatment decisions and lead to new targeted therapies."

The study is based on data from more than 300 patients with both early stage and advanced pancreatic cancer who participated in COMPASS, a first-of-its-kind clinical trial that is breaking new ground in discovery science and personalized pancreatic cancer treatment. COMPASS is enabled by advanced pathology laboratory techniques at UHN and OICR, and next generation sequencing at OICR.

"Most pancreatic cancer research is focused solely on early stage – or resectable – tumours, but in reality, pancreatic cancer is often found in patients after it has advanced and spread to other organs," says Notta. "COMPASS allowed us to look into these advanced cancers while treating these patients, develop a better understanding of the biology behind metastatic pancreatic cancer, and shed light on the mechanisms driving disease progression."

Interestingly, the Basal-like-A subtype, which had been difficult to observe before this study, was linked with a specific genetic abnormality. Most of the Basal-like-A tumours harboured several copies of a mutated KRAS gene, also known as a genetic amplification of mutant KRAS. The research group hypothesizes that some of the subtypes arise from specific genetic changes that occur as pancreatic cancer develops.

"This research opens new doors for therapeutic development," says Dr. Steven Gallinger, Co-Leader of OICR’s PanCuRx, Surgical Oncologist at UHN and Senior Investigator, Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital. "We look forward to capitalizing on the promise of these discoveries, building on our understanding of pancreatic cancer subtypes, and bringing new treatments to patients with the disease."

This research was supported by OICR through funding provided by the Government of Ontario, and by the Wallace McCain Centre for Pancreatic Cancer by the Princess Margaret Cancer Foundation, the Terry Fox Research Institute, the Canadian Cancer Society Research Institute, the Pancreatic Cancer Canada Foundation, the Canadian Friends of the Hebrew University and the Cancer Research Society (no. 23383).

On January 13, 2020 SHINE Medical Technologies LLC reported a strong 2019 year-end report, including significant progress with the construction of its medical isotope production facility, a robust year of fundraising and commercial advances in key geographic and product markets (Press release, Shine Medical Technologies, JAN 13, 2020, View Source;pk_kwd=2019-year-report [SID1234553206]).

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"2019 was SHINE’s most productive, successful year yet, driven by an incredibly dedicated team that moved the company forward in important ways," said Greg Piefer, founder and CEO of SHINE. "Our team’s progress on the construction of our production facility is the strongest signal to date that SHINE will play a big role in solving the global shortage of molybdenum-99."

SHINE-2019-Year-Highlights-Graphic
Rebar is lowered into place as construction continues on SHINE’s medical isotope production facility. SHINE broke ground for the facility in Janesville, Wis., last May. Excavation began last September and the first foundational concrete was poured later in the fall. Concrete that forms the structure of the facility continues to be poured.

Strong construction progress
SHINE broke ground for its medical isotope production facility in Janesville, Wis., last May. Excavation for the production facility began last September and the first foundational concrete was poured later in the fall. Concrete that forms the structure of the facility continues to be poured.

There are only four major facilities in the world that produce Mo-99, one of the most important isotopes relied on for heart stress tests, cancer staging and other medical applications. Chronic shortages of Mo-99 routinely and significantly affect the diagnosis and treatment of patients around the world.

When SHINE’s production facility begins producing Mo-99 at commercial scale in 2022, the facility will play a significant role in alleviating the worldwide shortages and their harmful impacts on patients. It will be capable of supplying more than one-third of the global patient need for Mo-99.

Continued investor support
Both new and long-time investors continued to express confidence in the company’s direction and progress last year. SHINE raised $125 million during 2019, including $50 million from leading global investment firm Oaktree Capital Management. The financing in part supports SHINE’s ongoing construction project and its work to commercialize diagnostic and therapeutic isotopes, including Mo-99 and lutetium-177 (Lu-177). The SHINE fundraising total includes an award of $15 million from the federal government.

"We are grateful for the strong, ongoing support of both our new high-quality institutional investors and the many early-stage investors who continue to support the company and provide additional capital," said Todd Asmuth, SHINE’s president and CFO. "During 2019, we were excited to welcome Oaktree Capital Management to our growing list of top-tier institutional investors. Oaktree has broad expertise in complex infrastructure projects like our production facility. It joined Deerfield Management, a leading health care investment firm, as one of our key partners. We also are appreciative of our partnership with the federal government. Its commitment to SHINE coupled with investments from both new and old investors were essential to our solid year of progress and will help us to boldly advance our plans as we move forward."

Therapeutics division focused on fundamental change to cancer treatment
The company created SHINE Therapeutics last October. The division is focusing initially on the development and commercialization of Lu-177. The isotope has the potential to fundamentally change the way cancer patients are treated. Studies have shown improved patient survival with Lu-177 treatment of neuroendocrine tumors and prostate cancer in patients who do not respond to other treatments. Lu-177 directly irradiates cancer cells after being delivered to the cancer site by a targeting molecule.

Last May, SHINE entered an agreement with IOCB Prague that provides the company with an exclusive global license to a novel technology that enables SHINE to produce therapeutically desirable non-carrier-added Lu‑177.

SHINE also achieved a number of other key milestones, including the following:

Commercial
• In September, SHINE established a direct presence in Europe with the appointment of industry expert Harrie Buurlage as SHINE’s vice president of European operations. Mr. Buurlage is leading the company’s effort to site, construct and run an isotope production facility in Europe. When the European facility begins production, SHINE will be capable of producing more than two-thirds of the global patient demand for Mo-99.
Corporate
• Paul Ryan, the former Speaker of the U.S. House of Representatives, joined the company’s board of directors in August. Mr. Ryan brings decades of national and international experience with complex health care, business, energy and other issues to SHINE’s board.
Production demonstrations
• During 2019, the company performed demonstrations of the neutron generator that will be at the heart of the production facility. Last June, SHINE and its sister company Phoenix LLC tested the first production-ready neutron generator over 5½ days, achieving greater than 99 percent uptime. The two companies last October announced that they had achieved a new world record for a nuclear fusion reaction in a steady-state system. The company’s production facility will house eight of these neutron generators when it is completed.

Regulatory
• The U.S. Nuclear Regulatory Commission began its official review of SHINE’s operating license application after accepting the application last October. SHINE submitted its operating license application to the commission last July. The submission of the application signaled the start of the company’s transition from the design and engineering phase to the construction and delivery phase.

"SHINE expects to continue its strong progress during 2020," Piefer said. "We will complete the construction of our main production building in Janesville; continue to develop lutetium-177, our first therapeutic product; and work to identify the site of our European facility. These and other 2020 goals support the continued advancement of SHINE’s purpose: to improve the world with nuclear technology with a commercially practical, growth based approach."

J.P. Morgan Healthcare Conference
Members of SHINE’s management team will be attending the annual J.P. Morgan Healthcare Conference. The conference is being held Jan. 13-16 in San Francisco. The SHINE team expects to meet with investors during the conference.