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.

On January 13, 2020 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported preliminary net revenues for 2019, as well as outlined key BPDCN market successes and upcoming commercial and clinical milestones (Press release, Stemline Therapeutics, JAN 13, 2020, View Source [SID1234553177]).

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Unaudited preliminary 2019 results include:

$43.2 million in estimated ELZONRIS net revenues for the year-ended December 31, 2019
$11.8 million in estimated ELZONRIS net revenues for the fourth quarter of 2019
The above financial information is based on preliminary unaudited information, is subject to adjustment, and does not present all information necessary for an understanding of the Company’s full-year and fourth quarter financial results for 2019. Stemline expects to report complete audited 2019 financial results on or before March 16, 2020.

Robert Francomano, Chief Commercial Officer of Stemline, stated, "We are very pleased with the solid uptake seen in the first year of the ELZONRIS launch, as we continue to successfully create, penetrate and grow a new market in BPDCN. Given the orphan nature and unique features of this disease, we believe patient starts were subject to significant quarterly variance – a phenomena that will likely continue throughout 2020. We are actively implementing a host of tactics to expand and further penetrate this emerging market."

Ivan Bergstein, CEO of Stemline, commented, "2019 was a transformational year for Stemline as we launched ELZONRIS, the first and only CD123 targeted agent and first agent ever approved for patients with BPDCN. We continue to pursue growth opportunities not only in BPDCN but also in a number of malignancies where targeting CD123 could provide therapeutic benefit. We look forward to data readouts in CMML, MF, and AML, including in patient subsets with high CD123, later this year and on into next year. Given our continued commercial and clinical progress, we look forward to a productive 2020 and beyond."

Corporate Highlights and Key Commercial and Clinical Milestones

BPDCN

$43.2 million in estimated, unaudited, net revenues for ELZONRIS in 2019
Marketing Authorization Application (MAA) under review by European Medicines Agency (EMA) for potential approval in the E.U.
Phase 1/2 trial of ELZONRIS in patients with BPDCN in the maintenance setting, post-stem cell transplant (SCT), has regulatory authorization to proceed; targeting treatment of the first patient in ~1Q20
Chronic Myelomonocytic Leukemia (CMML)

The CMML expansion cohort, Stage 3a, is open for enrollment of two patient populations: relapsed/refractory patients, and first-line, poor prognosis patients not expected to benefit from first line cytoreductive treatment
Results from Stage 3a is expected to inform the design of the subsequent Stage 3b confirmatory cohort for potential registration
We expect to report initial data from this trial in ~4Q20
Myelofibrosis (MF)

The MF cohort of the ongoing trial has been expanded to include 20-25 additional patients
We are evaluating relapsed/refractory patients and specific subsets of patients, including patients with monocytosis, thrombocytopenia, and CD123 positivity.
We expect to report updated data from this trial in ~4Q20
Acute Myeloid Leukemia (AML)

A Phase 1/2 trial of ELZONRIS in combination with other agents in patients with relapsed/refractory AML, treatment-naive AML unfit for chemotherapy, and high-risk myelodysplastic syndrome (MDS) is currently enrolling patients. We expect to provide data updates later this year.
About ELZONRIS
ELZONRIS (tagraxofusp), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.

On January 13, 2020 MacroGenics, Inc. (Nasdaq: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that the Company will present at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco on Thursday, January 16, 2020, at 9:00 a.m. PT (Press release, MacroGenics, JAN 13, 2020, View Source [SID1234553175]).

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An audio and slide webcast of the presentation may be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source The Company will maintain an archived replay of this webcast on its website for 30 days after the conference.

On January 13, 2020 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas"), through its wholly-owned subsidiary Universal Cells, Inc. and Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, reported that they have entered into a co-development and co-commercialization agreement to bring new stem-cell derived allogeneic T-cell therapies to people with cancer (Press release, Astellas, JAN 13, 2020, View Source [SID1234553157]).

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Astellas and Adaptimmune will agree on up to three targets and co-develop T-cell therapy candidates directed to those targets. These targets will exclude target specific T-cell products in pre-clinical or clinical trials or those developed for other partners at Adaptimmune. The collaboration will leverage Adaptimmune’s target identification and validation capabilities for generating target-specific T-cell Receptors (TCRs), chimeric antigen receptors (CARs), and HLA-independent TCRs that recognize surface epitopes independently of the HLA profile of the tumor cell. The collaboration will also utilize Astellas’ Universal Donor Cell and Gene Editing Platform it obtained through the acquisition of Seattle-based Universal Cells.

Adaptimmune has been collaborating with Universal Cells since 2015 on development of gene-edited iPSC cell lines, for which Adaptimmune has rights to develop and commercialize resulting T-cell therapy products using its proprietary process for generating T cells from stem cells without the use of feeder cell lines.

Astellas will fund research up until completion of a Phase 1 trial for each candidate. Upon completion of the Phase 1 trial for each candidate, Astellas and Adaptimmune will elect whether to progress with co-development and co-commercialization of the candidate, or to allow the other Party to pursue the candidate independently through a milestone and royalty bearing licence, with the agreement allowing for either company to opt out. The companies will each have a co-exclusive licence covering the co-development and co-commercialization of the product candidates within the field of T-cell therapy. If a candidate is developed by one company only, the appropriate licences will become exclusive to the continuing party.

"Astellas positions immuno-oncology as one of its strategic areas of primary focus, and it is engaged in the development of novel therapies for cancer patients using a new modality/technology," stated Naoki Okamura, Representative Director Corporate Executive Vice President, Chief Strategy Officer and Chief Financial Officer, Astellas. "In addition to NK cells, T-cells are an important component of cell therapy for immuno-oncology, and we look forward that this agreement with Adaptimmune will enable us to create new stem-cell derived allogeneic T-cell therapies for a variety of cancers, including solid tumors, in the future. We will continue to dedicate our efforts in delivering novel treatments for diseases with high unmet medical needs, pursuing cutting-edge science and technological advances."

"We are delighted to establish this significant co-development partnership with Astellas, which builds upon and substantially extends an existing collaboration focused on gene editing of iPSC cells," said Helen Tayton-Martin, Adaptimmune’s Chief Business Officer and Co-Founder. "This new collaboration may encompass both CAR-T and TCR T-cell approaches, including our novel HLA-independent TCR ("HiT") platform. It brings together highly complementary skills and expertise across the two organizations, and will enable the accelerated development of new, off-the-shelf T-cell therapy products for people with cancer."

Astellas will also have the right to select two targets and develop allogeneic cell therapy candidates independently. Astellas will have sole rights to develop and commercialize these products, subject to necessary licenses and the payment of milestones and royalties.

Under the terms of the agreement, Adaptimmune may receive up to $897.5 million in payments, including:

an upfront payment of $50 million.
development milestones totalling up to $73.75 million for each product if the collaboration product discovered in this partnership is co-developed and commercialized by both companies
Up to $147.5 million in milestone payments per product and up to $110 million in sales milestones for products developed unilaterally by Astellas.
In addition, Adaptimmune will receive research funding of up to $7.5 million per year.

Finally, Adaptimmune would receive tiered royalties on net sales in the mid-single to mid-teen digits.

Under the terms of the agreement, Astellas may receive up to $552.5 million, including:

Up to $147.5 million in milestone payments per product and up to $110 million in sales milestones
for products developed unilaterally by Adaptimmune.
In addition, Astellas would receive tiered royalties on net sales in the mid-single to mid-teen digits.

To the extent that Astellas and Adaptimmune co-develop and co-commercialize any T-cell therapy, they will equally share the costs of such co-development and co-commercialization, with the resulting profits from co-commercialization also shared equally. Further details governing co-development and co-commercialization will be articulated in a product-specific commercialization agreement.

The impact of this transaction on Astellas’ financial results in the fiscal year ending March 31, 2020 will be limited.