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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 Feb 1, 2018 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company") reported that its abstract has been accepted for a poster presentation at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 14-18, 2018 in Chicago, Illinois (Press release, Actinium Pharmaceuticals, FEB 1, 2018, View Source [SID1234523695]). The abstract showcases the potential of Actinium’s AWE Technology Platform, specifically, the ability of actinium-225 to enhance the in vivo efficacy of daratumumab, a CD38 targeting therapy that is marketed by Johnson & Johnson as Darzalex.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Per the abstract submission highlighted below, the Ac-225 labelled daratumumab at an equimolar concentration demonstrated superior antitumor activity to naked daratumumab in a highly predictive DAUDI model and provided a survival benefit. Additional details will be available at the time of the Annual Meeting. The Company had earlier presented initial in vitro data at ASH (Free ASH Whitepaper) which studied the effect of Actinium-225 labeled daratumumab on DAUDI, 28BM and 28PE cell lines at the 48, 72 and 96 hour time points as well as U226, a cell line that does not express CD38. The results showed that when daratumumab is labeled with Actinium-225, cell death was increased as much as ten-fold, approaching one-hundred percent cell death in certain cell lines and at certain time points, and in all three cell lines tested the Actinium-225 labeled daratumumab had higher cell death compared to naked daratumumab. In addition, immunogenicity was preserved with most or all of daratumumab’s CD38 targeting ability maintained, high rates of radioisotope labeling of the antibody from 82-85% was demonstrated, as was high rates of stability from 73-87% at various temperatures forty-eight hours post labeling.

Details on the poster are as follows:

Title: Conjugation of daratumumab with 225actinium greatly increases its antitumor activity against multiple myeloma tumors
Abstract Number: 760
Session Category: Experimental and Molecular Therapeutics

Sandesh Seth, Actinium’s Chairman and Chief Executive Officer said, "We are excited to build upon the already exciting data from our AWE Program and are looking forward to presenting new data from our continued efforts. The data we will present will exemplify Actinium’s expanding R&D capabilities and the potential of our AWE technology platform, which are now being spearheaded by our new Chief Scientific Officer, Dr. Dale Ludwig. This is the first AACR (Free AACR Whitepaper) that Actinium has presented data at and we look forward to a growing and impactful presence as we are committed to continuing to leverage our AWE technology and extending our capabilities both on behalf of our internal efforts but also for partners"

About Our Actinium Warhead Enabling Technology Platform

The Actinium Warhead Enabling (AWE) Technology Platform enables a highly potent and selective form of targeted therapy that combines the powerful alpha-emitting radioisotope actinium-225 with targeting agents, which are designed to seek out cancer cells in the body that express particular markers. Actinium-225 emits significant alpha radiation making it a potent treatment modality against targeted cancer cells while limiting damage to healthy tissues as its radiation travels extremely short distances in the body. When labeled to targeting agents, actinium-225 can be delivered directly to cancer cells where the high linear energy transfer resulting from the emission of alpha particles results in irreparable DNA double stranded breaks and ultimately cancer cell death. Despite this superior cell killing power, actinium-225 when delivered in a targeted manner is sparing of the surrounding environment in the body due to the short path length of its alpha-particle radiation and can result in a superior safety profile. Actinium Pharmaceuticals owns or has licensed the rights to several issued and pending patents that pertain to its AWE Technology Platform including technology to manufacture Actinium-225 in a cyclotron. In addition, the Company obtains actinium-225 from various sources such as the U.S. Department of Energy at Oak Ridge National Laboratories and has developed considerable know-how, expertise and validated processes related to production of Actinium Radio-Conjugates (ARC’s), management of the supply chain and dealing with various regulatory bodies. The AWE Technology Platform can be utilized to potentially improve the cell-killing power of targeting agents such as antibodies, peptides, Fab fragments, nanobodies etc. via labeling with Actinium-225. In addition to increased efficacy, these Actinium-225 enhanced targeting agents can offer optimized dosing or administration and in the case of approved targeting agents provide an opportunity to extend intellectual property protection by the creation of biobetters or improved versions of the approved agent. The Company’s Actinium Warhead Enabling (AWE) Program can be accessed by biopharmaceutical companies that are interested in creating biobetters through the utilization of the AWE Platform Technology. To learn more about the AWE Technology Platform or the AWE Program please contact Keisha Thomas, Ph.D., Corporate Development at [email protected].

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 Diffusion Pharmaceuticals Inc. (NASDAQ:DFFN) ("Diffusion" or "the Company"), a clinical-stage biotechnology company focused on extending the life expectancy of cancer patients, reported receipt of two patent application allowances relating to its lead compound trans sodium crocetinate ("TSC") in the U.S (Press release, Diffusion Pharmaceuticals, FEB 1, 2018, View Source [SID1234523684]). The allowances include claims for both method of use and composition of matter.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

U.S. patent application number 14/993,047 includes claims relating to treating a number of cancers including brain cancers such as glioblastoma, and cancer of the pancreas, using bipolar trans carotenoids, including TSC, along with chemotherapy and radiation therapy.

U.S. patent application number 14/642,703, includes claims relating to novel compositions of bipolar trans carotenoids, including TSC, for oral delivery.

"We have worked hard to ensure our discoveries are protected and are grateful to receive these patent application allowances. We look forward to these patents being issued in the coming months," said David Kalergis, Chief Executive Officer of Diffusion Pharmaceuticals. "We believe strong intellectual property protections are vital to Diffusion’s ability to compete in the marketplace and to attract potential strategic partners. As we progress our pivotal Phase 3 study in inoperable glioblastoma patients who are administered TSC along with their standard therapies, we feel that it is imperative that our proprietary position be protected to add increased value to the Company."

On February 1, 2018 Planegg – Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immune-oncology company focusing on the development of T cell immuno-therapies for the treatment of cancer, reported the grant of US patent 9,862,755 by the US Patent Office (USPTO) covering a high affinity T cell receptor with an epitope tag (Press release, MediGene, FEB 1, 2018, View Source [SID1234523689]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Applying an epitope tag to a high affinity T cell receptor potentially allows ex vivo and in vitro assessment of adoptively transferred T cell therapeutics. Potential applications of this technology could include the tracking of TCR-modified T cells through all steps of patient-individualized cell manufacturing processes, monitoring of TCR-modified T cells after administration to patients for proliferation and persistence in blood and tissue samples and removing of such tagged T cells through antibodies.
Medigene holds an exclusive license to the patent that was issued to Helmholtz Zentrum Munich and Max-Delbrück-Centrum for Molecular Medicine in Berlin.

Prof. Dolores Schendel, CEO and CSO of Medigene and co-inventor of the underlying technology, explains: "This US patent complements our broad patent portfolio in the space of T cell immunotherapies and represents one of many examples of the kinds of precise tools that Medigene is developing. This patent also supports our long-term thinking on using T cell-specific antibodies, TABs, as designer tools with multiple potential uses. TABs will help us to develop better and safer products in the future."

About Medigene’s TCR technology: The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex vivo).
Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, TecDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.