On February 2, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that on February 1, 2018 in PST Amgen Inc. made an announcement regarding the top-line results from its Global Phase 3 D-CARE trial in which Daiichi Sankyo also participated (Press release, Daiichi Sankyo, FEB 1, 2018, View Source [SID1234523682]). Amgen Inc.’s D-CARE, placebo-controlled trial, evaluated AMG162 (generic name: denosumab) as adjuvant treatment for women with high-risk, early stage breast cancer receiving standard of care neoadjuvant or adjuvant cancer therapy.

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The trial did not meet its primary endpoint of bone metastasis-free survival. Adverse events observed in patients treated with denosumab were generally consistent with the known safety profile.

Detailed results will be submitted to a future medical conference or publication.

Daiichi Sankyo continues to contribute the field of medicine to patients and medical professionals.

About denosumab

Daiichi Sankyo licensed the rights to develop and market denosumab in Japan from Amgen Inc. (United States) in 2007, and began the Japanese sales of a 60 mg preparation as a therapeutic agent for osteoporosis under the product name PRALIA Subcutaneous Injection 60 mg Syringe in June 2013. PRALIA received approval for additional indication as a treatment for inhibition of the progression of bone erosion associated with rheumatoid arthritis in July 2017. In April 2012, Daiichi Sankyo began sales of a 120 mg preparation as a therapeutic agent for bone complications stemming from multiple myeloma and bone metastases from solid tumors under the product name RANMARK Subcutaneous Injection 120 mg. RANMARK received approval for additional indication as a treatment for giant cell tumor of bone in May 2014.

About the D-CARE Study

The D-CARE (Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study of Denosumab as Adjuvant Treatment for Women with Early-Stage Breast Cancer at High Risk of Recurrence) study is an international, randomized, double-blind placebo-controlled trial of denosumab as adjuvant treatment for 4,509 women with early-stage breast cancer at high-risk of recurrence receiving standard of care neoadjuvant or adjuvant therapy. In this five year landmark study, patients were randomized to receive either subcutaneous denosumab 120mg or placebo every 3 or 4 weeks (Q3W or Q4W) for six months, followed by subcutaneous denosumab 120mg or placebo every three months for four and a half years, for a total treatment duration of five years (approximately 60 months). The primary endpoint for the study was bone metastasis-free survival and secondary endpoints included disease-free survival (DFS), DFS in the subset of post-menopausal women, overall survival and distant recurrence-free survival. Safety and tolerability were also evaluated.

On February 1, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported new data from an ongoing preclinical study of its investigational small molecule T-cell signaling pathway inhibitor (Press release, Corvus Pharmaceuticals, FEB 1, 2018, View Source;p=RssLanding&cat=news&id=2329771 [SID1234523681]).
Results showed that this orally-administered drug demonstrated safety and activity in companion dogs diagnosed with T-cell lymphoma. The data will be presented at the 10TH Annual T-Cell Lymphoma Forum in La Jolla, Calif., by Ryan Wilcox, M.D., Ph.D., assistant professor at the University of Michigan Comprehensive Cancer Center and an expert in peripheral and cutaneous T-cell lymphomas (PTCLs and CTCLs). The presentation is based on a study being led by Douglas Thamm, V.M.D., professor and director of clinical research at Flint Animal Cancer Center at Colorado State University.

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"We are very encouraged by the preliminary activity observed with our novel T-cell signaling pathway inhibitor in canine spontaneous T-cell lymphomas," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "Canine lymphomas, including T-cell malignancies, have cellular and clinical features very similar to human T-cell lymphomas, which are difficult to treat and for which new and improved therapies are desperately needed. Based on the results of this proof-of-concept study to date, we plan to continue enrolling animals in the study, and anticipate advancing the compound into a human clinical trial in approximately a year."

In the reported preclinical study, two dogs have been treated with Corvus’ T-cell signaling pathway inhibitor — one with PTCL and one with CTCL. Results showed evidence of antitumor activity in both animals. A complete response was achieved in the PTCL animal after 28 days of daily dosing, and a partial response was achieved in the CTCL animal within 14 days of the initiation of treatment. The compound was well tolerated in both dogs with no clinical signs or laboratory findings of toxicity.

"At Corvus, small molecule inhibitors of lymphocyte signaling is an area of expertise, and several of the key developers of ibrutinib are researchers here," said Joseph J. Buggy, Ph.D., co-founder and head of research at Corvus. "Similar to the mechanism of action of ibrutinib, our inhibitors are designed to selectively target important signaling pathways that we believe could drive the growth and survival of malignant lymphoma cells. This T-cell signaling pathway inhibitor is just one of multiple product opportunities in our R&D pipeline that target important immune cells and are designed to act on well-defined, very specific and crucial targets."

ABOUT CORVUS’ NOVEL T-CELL SIGNALING PATHWAY INHIBITOR
T-cell signaling is involved in T-cell activation, proliferation and differentiation, and plays a role in the replication and growth of various T-cell malignancies. Corvus’ novel T-cell signaling pathway inhibitor was designed to bind selectively to T-cells. It is orally bioavailable and has been shown to achieve cellular occupancy of the target in vivo in various animal models. It has been evaluated in preclinical safety studies.

The inhibition of specific molecular targets in T-cells may be of therapeutic benefit for patients with T-cell cancers — similar to the role of Bruton’s tyrosine kinase (BTK) in B-cells. BTK is now an established target for treating various B-cell lymphomas, and two BTK inhibitors, ibrutinib and aclarabrutinib, have been approved by the U.S. Food and Drug Administration for lymphoma indications. Proof-of-concept was demonstrated with ibrutinib in early preclinical studies in spontaneous canine B-cell lymphoma prior to initiation of human clinical trials.

ABOUT T-CELL LYMPHOMAS
Human T-cell lymphomas are a heterogenous group of difficult-to-treat malignancies. They include peripheral T-cell lymphomas (PTCLs), cutaneous T-cell lymphomas (CTCLs), anaplastic large cell lymphomas, acute lymphocytic lymphoma (ALL), angioimmunoblastic T-cell lymphoma (AITL) and others.

According to the Leukemia and Lymphoma Society, PTCLs comprise a diverse group of aggressive diseases. They generally affect people older than 60 years, although they can occur anytime during adulthood. Common signs and symptoms include fatigue, a painless swelling in the neck, armpit or groin (due to an enlarged lymph node), night sweats, rash and weight loss. Median survival is about two years. Current treatment for PTCLs includes chemotherapy, but most patients relapse.

CTCLs originate in the skin, with advanced stages defined by involvement of lymph nodes, peripheral blood and internal organs. CTCLs are treated with chemotherapy as well as topical therapies, including radiation to the skin.

On February 1, 2018 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company reported about an update on its ongoing Phase 1 clinical trial, called THINK (THerapeutic Immunotherapy with NKG2D), to assess the safety and clinical activity of its lead drug product candidate, CYAD-01, in seven refractory cancers, including both solid and hematologic cancers (Press release, Celyad, FEB 1, 2018, View Source [SID1234523680]). As of December 31, 2017, Celyad had treated 15 patients with CYAD-01 in the THINK trial. In six of the 10 patients treated at the per-protocol intended dose, Celyad observed signs of clinical activity ranging from Stable Disease (SD) to Complete Response (CR). In all cases, CYAD-01 was administered as a monotherapy without chemotherapy preconditioning. Based on the promising interim results of the THINK trial, the company plans to further evaluate CYAD-01 in a series of additional Phase 1 clinical trials in patients with acute myeloid leukemia (AML)and colorectal cancer (CRC).

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Celyad also announced that drug product manufactured using an improved manufacturing process designed to significantly increase the yield of T cells in the drug product that is produced, is now in the clinic. The first patient in the THINK trial to be administered drug product manufactured using the new manufacturing process was treated in late January 2018.

Christian Homsy, CEO of Celyad commented: "We are very pleased with our progress in the clinic during 2017, especially the observations of Stable Disease and Complete Response achieved at the lower doses and without chemotherapy preconditioning. Encouraged by these results, we are rapidly developing a robust clinical development plan for this product candidate in both AML and CRC. We are likewise excited to see drug product produced using our improved manufacturing process in the clinic. We anticipate that this process will enable us to significantly increase the yield of T cell expansion in the drug product we produce, while at the same time reducing process complexity and cost. We look forward to advancing our clinical development efforts in 2018, as we see to leverage our expertise in cell therapy technology for the benefit of critically ill patients in need."

The company also reported that, based on preliminary unaudited information and management estimates, at December 31, 2017, it had cash and cash equivalents and short term investments of approximately €34 million and is reconfirming guidance of a cash run rate into the first half of 2019.

THINK Trial Update (all data is as of December 31, 2017)

As of December 31, 2017, Celyad had treated 15 patients with CYAD-01 drug product in the THINK trial. Patients have been treated at the first and/or second dose level in both the solid and hematological tumor cohort of the dose escalation part of the trial. The company is currently enrolling patients for the third dose level phase in the solid tumor cohort and completing the second dose level phase in the hematological arm.

As of December 31, 2017, Celyad had not observed the same Grade 4 or above adverse event in two or more patients and no patient experienced a Grade 5 adverse event. No patient experienced an adjudicated Grade 4 or higher CRS adverse event or neurotoxic adverse event.

Of the 15 patients treated as of December 31, 2017, 10 were dosed at the per-protocol intended dose and five were treated at a dose lower than the per-protocol intended dose using drug product manufactured using a prior manufacturing method. In six of the 10 patients treated at the per-protocol intended dose Celyad observed signs of clinical activity ranging from Stable Disease (SD) to Complete Response (CR). Signs of clinical activity were observed in patients with AML, CRC and ovarian cancer. No signs of clinical activity were observed in patients treated with a dose lower than the per-protocol intended dose.

In all three AML patients treated at the per-protocol intended dose Celyad observed signs of clinical activity. A fourth AML patient was treated at a dose lower than the per-protocol intended dose and did not show signs of clinical activity. In two of four CRC patients treated at the per-protocol intended dose, Celyad observed signs of clinical activity. These two patients showed SD at the three-month follow-up date, both receiving the first dose level. A fifth CRC patient was treated at a dose lower than the per-protocol intended dose and did not show signs of clinical activity.

Manufacturing Update

Until recently, CYAD-01 drug product was manufactured using a process which did not consistently produce the required number of T cells in the drug product for the higher doses, resulting in some cases in an inability to manufacture drug product consistent with the protocol for the THINK trial. All 15 patients treated in the THINK trial as of December 31, 2017 were treated with drug product manufactured using this process. Of these 15 patients, 10 were dosed at the per-protocol intended dose and five were treated at a dose lower than the per-protocol intended dose due to an inability to obtain sufficient cell numbers in the drug product using this manufacturing method.

In response to these manufacturing challenges, Celyad modified the manufacturing process to include a monoclonal antibody (mAb) that inhibits NKG2D expression on the T cell surface during production. This method has the potential to yield significantly higher cell numbers. The THINK protocol has been amended for this new approach, and in the first three patient lot produced since this process was implemented, a very high cell yield was obtained.

The first patient in the THINK trial to be administered drug product manufactured using the mAb process was treated in late January 2018. The data from this patient is still emerging, but based on a preliminary review, the patient experienced an adverse event consistent with those observed in patients treated with drug product manufactured using the prior method, specifically hypoxia, which may or may not be adjudicated to be the result of CRS. Given that the drug product was administered in late January, it is too early to assess signs of clinical activity in this patient.

C-Cure

Until mid-2016, Celyad was focused on the development of a cardiovascular drug product candidate called C-Cure, an autologous cell therapy for the treatment of patients with ischemic heart failure. This program was funded in part through various research programs from the Walloon Region of Belgium. In June 2016, Celyad reported topline results from a Phase 3 clinical trial for this drug product candidate. Following the announcement of these results, the company explored strategic options to further develop and commercialize C-Cure, while the company focused on its CAR-T oncology drug product candidates. In December 2017, Celyad notified the Walloon Region of its decision not to exploit the results of this program in exchange for a cancellation of the loans of the Region to the Company.

On February 1, 2018 Celgene Corporation (NASDAQ: CELG) reported that it plans to present at two upcoming investor conferences where Celgene management will provide an overview of the Company (Press release, Celgene, FEB 1, 2018, View Source [SID1234523678]). The conferences will be webcast live and will be available in the Investor Relations section of the Company’s website at www.celgene.com.

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Thursday, February 15, 2018, Celgene will present at the Leerink Partners Global Healthcare Conference in New York City at 1:30 pm ET

Wednesday, February 21, 2018, Celgene will present at the RBC Capital Markets 2018 Global Healthcare Conference in New York City at 11:30 am ET

On February 1, 2018 Atossa Genetics Inc. (NASDAQ:ATOS), a clinical-stage pharmaceutical company developing novel therapeutics and delivery methods for breast cancer and other breast conditions, reported additional findings from its Phase 1 study of Atossa’s proprietary oral Endoxifen (Press release, Atossa Genetics, FEB 1, 2018, View Source [SID1234523677]). Endoxifen is an active metabolite of the FDA-approved drug tamoxifen, which is currently used to treat breast cancer and for breast cancer prevention in high-risk patients.

The additional findings from the oral arm of the Endoxifen Phase 1 study are summarized as follows:

The median time for patients in the study to reach the steady-state serum levels of Endoxifen while taking daily doses of Atossa’s oral Endoxifen was 7 days. Published literature indicates that it takes approximately 50-200 days for patients to reach steady-state Endoxifen levels when taking daily doses of oral tamoxifen.

The median time for patients in the study to reach the maximum serum level of Endoxifen after taking Atossa’s oral Endoxifen was ranged from 4 to 8 hours (depending on dose). The 4 mg dose of Endoxifen produced a maximum serum level of Endoxifen in 4 to 8 hours at levels above the generally accepted threshold for a therapeutic effect on estrogen-dependent breast cancer.
"These additional findings are important for several reasons," commented Steve Quay, Ph.D., MD, CEO and President of Atossa. "Breast cancer patients do not typically want to wait weeks or even months for the current standard of care, oral tamoxifen, to take effect. Our study data indicates that our proprietary oral Endoxifen reaches a steady-state in about 7 days, while the literature indicates that it can take 50-200 days for tamoxifen to reach a steady-state – keeping in mind that a breast cancer tumor can double in size in as little as 29 days. Not only does it take up to several months for oral tamoxifen to take effect, oral tamoxifen also does not benefit up to 50% of patients, partly because many patients cannot metabolize tamoxifen. For these reasons, we believe our oral Endoxifen may reduce the incidence of this deadly disease and fundamentally change the paradigm for breast cancer treatment," added Dr. Quay.

The additional findings will also be discussed during the conference call today at 4:30 pm EST. Due to expected high call attendance, participants are asked to preregister for the call through the following link: View Source Please note that registered participants will receive their dial in number upon registration and will dial directly into the call without delay. Those without internet access or who are unable to pre-register may dial in by calling: 1-844-824-3830 (domestic), 1-412-317-5140 (international) and Canada Toll Free: 1-855-669-9657. Callers should ask to be joined into the Atossa Genetics call.

The conference call will also be available through a live webcast at www.atossagenetics.com. Details for the webcast may be found on the Company’s IR events page at View Source

Management will answer pre-submitted questions gathered prior to the conference call in the Question and Answer period of the call. Interested parties may submit questions for management’s consideration prior to the call by submitting them in writing to Atossa Genetics’ Investor Relations at [email protected].

A replay of the call will be available approximately one hour after the end of the call through March 1, 2018. The replay can be accessed via Atossa’s website or by dialing 877-344-7529 (domestic) or 412-317-0088 (international) or Canada Toll Free at 855-669-9658. The replay access code is 10116753.

The objectives of Atossa’s double-blinded, placebo-controlled, Phase 1 study of 48 healthy female subjects were to assess the pharmacokinetics of proprietary formulations of both oral and topical Endoxifen dosage forms as single (oral) and repeat (oral and topical) doses, as well as to assess safety and tolerability. Preliminary results from the study, which were announced on September 14, 2017 and October 25, 2017, showed that all objectives of the study were successfully met: there were no clinically significant safety signals and no clinically significant adverse events and both the oral and topical Endoxifen were well tolerated. In the topical arm of the study, low but measurable Endoxifen levels were detected in the blood in a dose-dependent fashion. In the oral arm of the study, participants exhibited dose-dependent Endoxifen levels that met or exceeded the published therapeutic level.

Atossa is developing proprietary Endoxifen with two routes of delivery anticipated to address two distinct patient populations: oral Endoxifen for breast cancer survivors and topical Endoxifen for women with a condition called mammographic breast density (or, MBD). When a patient is treated for breast cancer, doctors typically prescribe oral tamoxifen for 5-10 years to reduce the risk of recurrent and new tumors. Tamoxifen can have uncomfortable as well as serious side effects. Perhaps more importantly, not all patients benefit from tamoxifen therapy due to their inability to effectively metabolize tamoxifen into Endoxifen. Recent research continues to confirm the key role Endoxifen plays in reducing the risk of recurrent and new breast cancer in these patients. It is estimated that more than one million breast cancer survivors in the U.S. are recommended to take tamoxifen. Atossa is developing oral Endoxifen for these patients who are "refractory" to tamoxifen meaning that they are not benefiting from tamoxifen.

There is no FDA-approved treatment for MBD, which affects more than ten million women in the U.S. It is well accepted that MBD increases the risk of breast cancer, which is why 30 states currently require that a finding of MBD be reported to the patient, physician or both. It is believed that not only does MBD make mammography less effective because MBD can hide cancerous tumors, but also the tissue itself may be more prone to develop cancer. For these reasons, Atossa is developing topical Endoxifen as a potential treatment for MBD.

Results from Atossa’s Phase 1 study have paved the way for upcoming Phase 2 studies: a study using Atossa’s proprietary topical Endoxifen to treat MBD which will be performed at South General Hospital in Stockholm and a study using Atossa’s proprietary oral Endoxifen to treat women who are refractory to tamoxifen. We plan to open both of these studies in the first quarter of 2018.

Atossa has also started a program to deliver Chimeric Antigen Receptor Therapy, or CAR-T, cells into the ducts of the breast for the potential targeted treatment of breast cancer. This is a novel approach using Atossa’s proprietary intraductal microcatheter technology for the potential transpapillary, or "TRAP," delivery of T-cells that have been genetically modified to attack breast cancer cells. We believe this method has several potential advantages including the reduction of toxicity by limiting systemic exposure of the T-cells; improved efficacy by placing the T-cells in direct contact with the target ductal epithelial cells that are undergoing malignant transformation; and, lymphatic migration of the CAR-T cells potentially extending their cytotoxic actions into the regional lymph system, which could limit tumor cell dissemination. We are also using our intraductal microcatheters in a Phase 2 study at Montefiore Medical Center in New York where we are targeting the delivery of Fulvestrant to the site of early stage breast cancer and ductal carcinoma in situ.

Atossa is developing its products to reduce the risk of developing breast cancer and to provide new approaches to effectively treat breast cancer patients in a cost-effective and safer manner. A study conducted by Defined Health, a leading market research firm, estimates that the potential market for Endoxifen exceeds $1 billion in annual sales and the potential market for Atossa’s intraductal microcatheters to delivery therapeutics exceeds $800 million as a treatment and replacement for surgery.

CAR-T has been the subject of much attention recently. In October 2017, pioneer CAR-T company Kite Pharma was acquired for $11.9 billion by Gilead; in August 2017 Novartis received the first FDA approval in the CAR-T field for Kymriah for the treatment of B-cell Acute Lymphoblastic Leukemia; and in January 2018 Celgene Corporation announced the acquisition of Juno Therapeutics for $9 billion.

Atossa’s 2018 potential milestones include:

First quarter of 2018 – opening the Phase 2 Study of topical Endoxifen to treat MBD at Stockholm South General Hospital in Sweden (which we plan to complete in 2018).
First quarter of 2018 – opening the Phase 2 Study of oral Endoxifen to treat patients who are not responding to Tamoxifen (which we plan to complete in 2018).
Second half of 2018 – commencing one or more studies administering TRAP CAR-T with our microcatheters.
Throughout 2018 – continuing our Phase 2 study administering Fulvestrant with our microcatheters.
The American Cancer Society (ACS) estimates that approximately 250,000 women will be diagnosed with breast cancer in the United States this year and that approximately 40,000 will die from the disease. It is the second leading cause of cancer death in American women. Although about 100 times less common than women, breast cancer also affects men. The ACS estimates that the lifetime risk of men getting breast cancer is about 1 in 1,000; 2,470 new cases of invasive breast cancer will be diagnosed; and 460 men will die from breast cancer in 2017.