On April 21, 2017 GlycoMimetics, Inc. (NASDAQ: GLYC) reported that the company will provide an update on clinical data from its Phase 1 and 2 studies of GMI-1271 at the 2017 American Society for Clinical Oncology in Chicago (Press release, GlycoMimetics, APR 21, 2017, View Source [SID1234518662]). GMI-1271 is an antagonist of E-selectin, for which prior data has shown an emerging and differentiated efficacy profile.

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Details of the ASCO (Free ASCO Whitepaper) presentations include:

Abstract #2520

Poster discussion. DeAngelo, D.J., et al. "GMI-1271, a Novel E-Selectin Antagonist, in Combination with Chemotherapy in Relapsed/Refractory AML." Session Title: Poster Discussion Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics, Monday, June 5, 11:30 a.m.-12:45 p.m. CT.

Presenter: Daniel J. DeAngelo, MD, PhD, Dana Farber Cancer Institute Director of Clinical and Translational Research, Adult Leukemia, and Institute Physician ; Harvard Medical School Associate Professor of Medicine

Abstract #2560

Poster. DeAngelo, D.J. et al. "GMI-1271, a Novel E-Selectin Antagonist, Combined with Induction Chemotherapy in Elderly Patients with Untreated AML." Session Title: Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics. Monday, June 5, 8:00-11:30 a.m. CT.

Presenter: Dr. DeAngelo

The ASCO (Free ASCO Whitepaper) Annual Meeting 2017 takes place from June 2 to 5, at McCormick Place in Chicago. Meeting abstracts are available at ASCO (Free ASCO Whitepaper)’s website.

On April 21, 2017 Tiziana Life Sciences plc (AIM: TILS, the "Company"), a clinical stage biotechnology company developing targeted drugs for cancer and autoimmune diseases, reported that a research article detailing the use of the Company’s lead compound, milciclib, has been published in the prestigious, peer-reviewed journal Cancer Chemotherapy and Pharmacology, entitled: "Phase I Dose-Escalation Study of Milciclib, A Novel Inhibitor of Cyclin Dependent Kinases (CDKs), in Combination with Gemcitabine in Patients with Refractory Solid Tumors"[1] (Press release, Tiziana Life Sciences, APR 21, 2017, View Source [SID1234518663]).

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In this phase I clinical trial, 16 patients with advanced metastatic tumours, refractory to existing cancer therapies, were enrolled. The treatment regimen consisted of oral treatment with milciclib once daily for 7 days on/7 days off in a 4-week cycle with concomitant gemcitabine administered intravenously once weekly for 4 weeks. This combination treatment regimen showed positive clinical responses in approximately 36% of patients, including gemcitabine refractory patients. One patient with non-small cell lung carcinoma (NSCLC), showed partial response and four patients (one each with thyroid, prostatic, pancreatic carcinoma and peritoneal mesothelioma) showed long-term disease stabilisation for up to 14 months. In previous clinical studies, oral treatment with milciclib, was found be safe and well tolerated in patients with thymoma and thymic cancers.

Gabriele Cerrone, Chairman of Tiziana Life Sciences, commented: "Following the generation of encouraging phase I clinical data with milciclib, reported in this important publication, we are rapidly moving forward with further evaluation of the drug as an oral treatment in phase IIa clinical trials for patients with refractory hepatocellular carcinoma (HCC), which is a significant unmet medical need. It is noteworthy that the combination treatment regimen used in the phase I study also exhibited positive clinical activity in patients who were previously resistant to treatment with gemcitabine, a drug widely used as a partner in combination therapies for treatment of refractory cancers. This suggests that milciclib may have therapeutic potential in combination with other existing therapies."

[1] Aspeslagh, S., Shailubhai, K., Bahleda, R. et al. Cancer Chemother Pharmacol (2017). doi:10.1007/s00280-017-3303-z

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About Milciclib

Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases (CDKs) such as CDK1, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signalling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. Oral treatment with milciclib was found to be effective in reducing tumour growth in animal models of HCC, possibly through downregulation of miR-221 and miR-222. In a phase I study, oral treatment with milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in thymic carcinoma, pancreatic carcinoma and colon cancer.


About Gemcitabine

Gemcitabine, a well-known nucleoside analogue sold under the brand name Gemzar, is a widely used chemotherapeutic drug used either as a monotherapy or in combination with other anti-cancer agents for treatment of a wide range of solid tumours. Synergism between CDK inhibitors and gemcitabine has been shown in animal studies as well as in a phase I trial with cancer patients.

About Cancer Chemotherapy and Pharmacology

Cancer Chemotherapy and Pharmacology is a journal addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels. Primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists. The journal is published by Springer, which is part of Springer Nature, a global publisher that serves and supports the research community.

On April 21, 2017 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that an abstract describing results from its global Phase 3 clinical trial evaluating aldoxorubicin versus investigators’ choice in patients with relapsed and refractory soft tissue sarcomas (STS) has been selected for an oral presentation at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2017 in Chicago (Press release, CytRx, APR 21, 2017, View Source [SID1234518660]).

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In addition, updated data from the Company’s ongoing Phase 1/2 clinical trial combining aldoxorubicin with ifosfamide/mesna in patients with first-line soft tissue sarcomas has also been selected for a poster presentation.

"We look forward to presenting the more detailed and updated global Phase 3 results to the medical community at ASCO (Free ASCO Whitepaper) this year," said Daniel Levitt, M.D., Ph.D., Chief Operating Officer and Chief Medical Officer of CytRx. "The Phase 3 trial and the combination trial of aldoxorubicin with ifosfamide continue to build on our prior studies showing the utility of aldoxorubicin as a treatment for patients with STS. These trials, together with our other clinical and pre-clinical studies of aldoxorubicin, will support our planned New Drug Application submission."

Details for the presentations at ASCO (Free ASCO Whitepaper) 2017:

Oral Presentation

Title: Phase III study of aldoxorubicin vs investigators’ choice as treatment for relapsed/refractory soft tissue sarcomas
Presenter: Sant Chawla, M.D., F.R.A.C.P., Director of the Sarcoma Oncology Center in Santa Monica, and Principal Investigator
Abstract #: 11000
Session Title: Oral Abstract Session: Sarcoma
Location: S100bc
Date and Time: Friday, June 2, 2017; 3:00pm-6:00pm CT

Poster Presentation

Title: Administration of aldoxorubicin and 14 days continuous infusion of ifosfamide/Mesna in metastatic or locally advanced sarcomas.
Presenter: Frederick C. Eilber, M.D., Director of the UCLA Sarcoma Translational Research Program within the Jonsson Comprehensive Cancer Center
Abstract #: 11051
Session Title: Poster Session: Sarcoma
Location: Hall A
Poster board#: 374
Date and Time: Sunday, June 4, 2017; 8:00am-11:30am CT

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. It can arise anywhere in the body at any age. STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer. According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.

About Aldoxorubicin

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 6,500 mg/m2 of doxorubicin equivalents. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.

On April 21, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company developing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that preliminary data from a Phase Ib combination study of its PD-1 antibody BGB-A317 and its PARP inhibitor BGB-290 in patients with advanced solid tumors will be presented in a poster discussion session at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, BeiGene, APR 21, 2017, View Source [SID1234518659]). The ASCO (Free ASCO Whitepaper) Annual Meeting will take place June 2–6, 2017 in Chicago, Illinois. Details of the presentation are provided below.

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Abstract #3013

Title: A Phase 1b Study of the Anti-PD-1 Monoclonal Antibody BGB-A317 (A317) in Combination with the PARP Inhibitor BGB-290 (290) in Advanced Solid Tumors.

Presenter: Michael Friedlander, MD, PhD
Poster Discussion Session: Developmental Therapeutics – Immunotherapy
Date: June 5, 2017
Time: 4:45–6:00 PM CT
Location: Hall D1, McCormick Place
Poster Board: #108

About BGB-A317

BGB-A317 is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. BGB-A317 has high affinity and specificity for PD-1, and we believe it is differentiated from the currently approved PD-1 antibodies with the ability to bind Fc gamma receptor I specifically engineered out. BGB-A317 is being developed as a monotherapy and in combination with other therapies for the treatment of various cancers.

About BGB-290

BGB-290 is a potent and highly selective inhibitor of PARP1 and PARP2. BGB-290 is being developed as a monotherapy and in combination with other therapies for the treatment of several cancers including ovarian cancer, prostate cancer, breast cancer, glioblastoma multiforme, small cell lung cancer, and gastric cancer.

On April 21, 2017 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a biopharmaceutical company focused on developing meaningful therapies for patients with severe and life-threatening diseases, reported that it has entered into a clinical trial collaboration agreement with Merck (known as MSD outside the United States and Canada), to evaluate Atara Bio’s allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL), or ATA129, in combination with Merck’s anti-PD-1 (programmed death receptor-1) therapy, KEYTRUDA (pembrolizumab), in patients with platinum resistant or recurrent EBV-associated NPC (Press release, Atara Biotherapeutics, APR 21, 2017, View Source [SID1234518658]). The Phase 1/2 trial will evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the combination and is planned for initiation in 2018.

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Atara Bio’s ATA129 is an investigational therapy in which a healthy donor’s T-cells are stimulated to recognize EBV antigens, or viral proteins, expressed in the cells of certain liquid and solid tumors. ATA129 has previously been evaluated as a single agent in Phase 1 and 2 trials that enrolled patients with a variety of EBV-positive malignancies including 14 patients with chemotherapy refractory, metastatic NPC. In these trials, evidence of radiographic response was observed and EBV-CTLs were also shown to expand after administration without concomitant lymphodepleting chemotherapy. Recent studies suggest that EBV upregulates the transcription of PD-L1 in EBV-associated solid tumors such as NPC and gastric cancer, suggesting the potential for synergy in combination with anti-PD-1 therapies, such as KEYTRUDA.

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

"Both ATA129 and KEYTRUDA have shown evidence of objective radiographic responses in NPC, and there is a strong biologic rationale to combine these therapies as their complementary mechanisms of action may enhance the anti-tumor activity," said Chris Haqq, M.D., Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer of Atara Bio.

The collaboration agreement is between Atara Biotherapeutics, Inc. and Merck Sharp & Dohme B.V. Under the agreement, the trial will be sponsored by Atara Bio. Additional details of the collaboration were not disclosed.

About ATA129

EBV is associated with a wide range of hematologic malignancies and solid tumors, as well as certain autoimmune conditions such as multiple sclerosis. T-cells are a critical component of the body’s immune system and can be harnessed to counteract viral infections and some cancers. By focusing the T-cells on specific proteins involved in the cancers and infections, the power of the immune system can be employed to combat these diseases. Atara Bio’s ATA129 utilizes a technology in which T-cells are collected from the blood of third-party donors and then exposed to EBV antigens. The resulting activated T-cells are then expanded, characterized, and stored for future therapeutic use in an appropriate partially human leukocyte antigen, or HLA, matched patient, providing an allogeneic, cellular therapeutic option for patients. In the context of EBV infection, ATA129 finds the cells expressing EBV and kills them. ATA129 is currently being studied in ongoing Phase 2 clinical trials in patients with EBV-associated cancers, including EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD) and NPC. ATA129 is also available to eligible patients with EBV-positive tumors through an ongoing multicenter expanded access protocol trial. Atara Bio is planning to initiate two Phase 3 trials of ATA129 in patients with rituximab-refractory EBV-PTLD following either hematopoietic cell transplant (HCT) or solid organ transplant (SOT).