(Press release, NantBioScience, SEP 15, 2014, View Source [SID:1234503331])

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(Press release, NantBioScience, SEP 15, 2014, View Source [SID:1234505862])

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On September 15, 2014 SignalRX Pharmaceuticals Inc., focused on developing more effective oncology drugs though molecular design imparting multiple target inhibition, reported the presentation of scientific data on the Company’s proprietary dual inhibitor program in oncology (Press release, SignalRx, SEPT 15, 2014, View Source [SID1234527331]). The presentation by Dr. Donald Durden, MD, PhD, founder and CEO of SignalRx was made at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference on Targeting the PI3K-mTOR Network in Cancer at the Sheraton Philadelphia Downtown Hotel, Philadelphia, Pennsylvania.

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The presentation highlighted the discovery and early development of patented new molecules such as SF2523 that inhibit kinase targets such as PI3 kinase (PI3K) while also blocking epigenetic targets such as bromodomain proteins. SignalRx presented in vivo evidence of efficacy without toxicity in mouse cancer models with SF2523 alleviating potential theoretical safety concerns arising from inhibiting multiple key nodal cancer targets with one drug.

The ability to safely simultaneously inhibit multiple key targets is highly sought after in cancer treatment to maximize efficacy and prevent resistance. Replacing several combinations of drugs with one drug hitting multiple targets is also being driven by exploding oncology drug costs to patients and to the health care system. SignalRx compounds are being developed as next generation PI3K inhibitors and it has now been shown that they also potently inhibit certain bromodomain proteins such as BRD4. SF2523 is a lead dual inhibitor compound and has been demonstrated to: 1) inhibit proliferation across 18 different cancer cell lines; 2) induce apoptosis in neuroblastoma cells, renal cell carcinoma cells, multiple brain cancer cell lines including patient-derived samples; 3) block angiogenic signaling and blood vessel production in vivo; 4) inhibit cancer stem cells in breast and human medulloblastoma patient cells; 5) exhibit potent antitumor efficacy and anti-metastatic effects without toxicity in renal cell carcinoma xenograft models, neuroblastoma mouse models, orthotopic pancreatic cancer model and Lewis lung cancer models.

Bromodomain proteins bind to acetylated lysine groups on chromatin and promote gene transcription. SignalRx’s compounds act as acetyl lysine mimetics and prevent the bromodomain protein from binding to chromatin. This mechanism of action is distinct from the compound’s PI3K inhibition where the inhibitors bind in the ATP catalytic site of the kinase. This allows for the first time simultaneous control of both the PI3K pathway and the transcription of certain genes mediated by bromodomain proteins. An example of the utility of this approach to solve unmet medical needs is to block the tumor suppressor gene MYC which is a driver in many cancers including CLL and multiple myeloma and for which small molecule inhibitors have been elusive. Inhibition of PI3K increases the cellular degradation of MYC protein while BRD4 inhibition decreases the transcription (production) of MYC protein. Use of SignalRx’s dual PI3K/BRD4 inhibitors provides a unique and effective approach to block the action of MYC via two orthogonal mechanisms demonstrated with lead compound SF2523 to be efficacious without toxicity in mouse models.

These new compounds are broadly covered by composition-of-matter U.S. Patent No. 8,557,807 entitled "Thienopyranones as kinase inhibitors" issued October 15, 2013. Additional information on preparation and structure-activity-relationships of these compounds were recently published in the Journal of Medicinal Chemistry (February 14th 2013 issue, volume 56, pages 1922-1939).

"The discovery of SF2523 which inhibits both PI3K and BRD4 represents a major step forward in designing anticancer agents to be as effective as possible" said Donald L. Durden, MD, PhD,. "Additionally, the problem of early stage clinical trial evaluation of multiple combinations is solved by this approach by consolidating at least two of the combination partners into one drug. Moreover, because two separate drugs will always suffer from differing cell penetration, metabolism, and pharmacokinetics our approach of one molecule hitting two critical targets in the same cell is the only way to ensure that desired simultaneous blockage of multiple key signaling pathways is achieved in vivo."

On September 11, 2014 CANCER RESEARCH UK and Cancer Research Technology (CRT), the charity’s development and commercialisation arm, have reached an agreement with Asterias Biotherapeutics, Inc. (OTCBB: ASTY), a biotechnology company in the emerging field of regenerative medicine, to take forward Asterias’ novel immunotherapy treatment AST-VAC2 into clinical trials in subjects with non-small cell lung cancer (Press release BioTime, SEP 11, 2014, View Source;p=RssLanding&cat=news&id=1966042 [SID:1234500740]).

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AST-VAC2 represents the tenth treatment to enter Cancer Research UK’s Clinical Development Partnerships* (CDP) scheme, with six having progressed into the clinic to date. CDP is a joint initiative between Cancer Research UK’s Drug Development Office (DDO) and Cancer Research Technology, to develop promising anti-cancer agents which pharmaceutical companies do not have the resources to progress through early phase clinical trials.

AST-VAC2 is a non-patient specific (allogeneic) cancer vaccine designed to stimulate patients’ immune systems to attack telomerase, a protein that is expressed in over 95 percent of cancers but is rarely expressed in normal adult cells.

The vaccine was developed following successful early phase clinical trials of a similar, patient specific (autologous) Asterias vaccine, called AST-VAC1, which was derived from patients’ blood cells and tested in prostate cancer and acute myeloid leukemia.

Unlike AST-VAC1, and other autologous (patient specific) vaccines that are developed from a patient’s own cells, AST-VAC2 is derived from human embryonic stem cells (hESCs), meaning it can be produced on a large scale and stored ready for use, rather than having to produce a specific version of the drug for each patient.

The trial of AST-VAC2 will evaluate the safety and toxicity of the vaccine, feasibility, stimulation of patient immune responses to telomerase and AST-VAC2, and clinical outcome after AST-VAC2 administration in patients with resected early-stage lung cancer and in patients with advanced forms of the disease.

Pedro Lichtinger, Asterias’ chief executive officer, said: "The Asterias collaboration with Cancer Research UK’s Drug Development Office and CRT represents a major step in advancing our proprietary dendritic cell platform for the potential benefit of patients.

"AST-VAC2 is based on a specific mode of action that is complementary and potentially synergistic to other immune therapies. We are delighted to partner with Cancer Research UK to advance this important platform through Phase 1/2 clinical trials. Cancer Research UK’s Drug Development Office has the global recognition of having the quality, capability and track record of successfully advancing development programs. We are excited about the possibility of favorably impacting the lives of patients across multiple cancers and are proud to be working with Cancer Research UK."

Under the agreement, Asterias will complete development of the manufacturing process for AST-VAC2. Cancer Research UK will then produce the vaccine and conduct the phase 1/2 clinical trial in the UK. On completion of the clinical trial, Asterias will have an exclusive first option to acquire a license to the data from the trial on pre-agreed terms including an upfront payment, milestones and royalties on sales of products. If Asterias declines this option, CRT will then have an option to obtain a license to Asterias’ intellectual property to continue the development and commercialisation of AST-VAC2 and related products in exchange for a revenue share to Asterias of development and partnering proceeds.

Dr. Jane Lebkowski, president of research and development at Asterias, said: "The use of human embryonic stem cells to derive allogeneic dendritic cells for cancer immunotherapy has the potential to dramatically improve the scalability, consistency, and feasibility of cellular cancer vaccines. We believe this collaboration will enable the acceleration of clinical studies of AST-VAC2 and the collection of important proof-of-concept data for the entire human embryonic stem cell-derived dendritic cell immunotherapy platform."

Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said: "Recent advances in cancer immunotherapy have demonstrated the exciting potential of these treatments to improve outcomes in devastating diseases such as lung cancer. Better treatment options for lung cancer are badly needed and it is through collaborations such as this that we can save more lives sooner."

On September 11, 2014 Cancer Research UK and Cancer Research Technology (CRT), the charity’s development and commercialisation arm, reported an agreement with Asterias Biotherapeutics, Inc. (OTCBB: ASTY), a biotechnology company in the emerging field of regenerative medicine and a subsidiary of BioTime, Inc. (NYSE MKT: BTX), to take forward their novel immunotherapy treatment AST-VAC2 into clinical trials with non small cell lung cancer patients (Press release, Cancer Research Technology, SEP 11, 2014, View Source [SID1234523224]).

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

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This is the tenth treatment to enter Cancer Research UK’s Clinical Development Partnerships* (CDP) scheme, with six having progressed into the clinic to date. CDP is a joint initiative between Cancer Research UK’s Drug Development Office (DDO) and Cancer Research Technology, to develop promising anti-cancer agents which pharmaceutical companies do not have the resources to progress through early phase clinical trials.

AST-VAC2 is a non-patient specific (allogeneic) cancer vaccine designed to stimulate patients’ immune systems to attack telomerase, a protein that is expressed in over 95 percent of cancers but is rarely expressed in normal adult cells.

The vaccine was developed following successful early phase trials of a similar Asterias drug, called AST-VAC1, which was designed to treat acute myeloid leukemia and derived from patients’ blood cells.

Unlike AST-VAC1, and other autologous (patient specific) vaccines that are developed from a patient’s own cells, AST-VAC2 is derived from human embryonic stem cells (hESCs), meaning it can be produced on a large scale and stored ready for use, rather than having to produce a specific version of the drug for each patient.

The trial of AST-VAC2 will evaluate the safety and toxicity of the vaccine, feasibility, stimulation of patient immune responses to telomerase and AST-VAC2, and clinical outcome after AST-VAC2 administration in patients with either resected early-stage, or advanced forms of lung cancer.

Pedro Lichtinger, Asterias’ chief executive officer, said: "The Asterias collaboration with Cancer Research UK’s Drug Development Office represents a major step in advancing our proprietary dendritic cell platform for the potential benefit of patients.

"AST-VAC2 is at the forefront of cell-based immune therapies. It is based on a unique mode of action that is complementary and potentially synergistic to other immune therapies. We are delighted to partner with Cancer Research UK to advance this important platform through Phase 1/2 clinical trials. Cancer Research UK’s Drug Development Office has the global recognition of having the quality, capability and track record of successfully advancing development programs. We are excited about the possibility of favorably impacting the lives of patients across multiple cancers and are proud to be working with Cancer Research UK."

Under the agreement, Asterias will complete development of the manufacturing process for AST-VAC2. Cancer Research UK will then produce the vaccine and conduct the phase 1/2 clinical trial. On completion of the clinical trial, Asterias will have an exclusive first option to acquire the data from the trial. If Asterias declines this, CRT will then have an option to obtain a license to Asterias’ intellectual property to continue the development and commercialisation of AST-VAC2 and related products in exchange for a revenue share to Asterias of development and partnering proceeds.

Dr Jane Lebkowski, president of R&D at Asterias, said: "The use of human embryonic stem cells to derive allogeneic dendritic cells for cancer immunotherapy has the potential to dramatically improve the scalability, consistency, and feasibility of cellular cancer vaccines. We believe this collaboration will enable the acceleration of clinical studies of AST-VAC2 and the collection of important proof-of-concept data for the entire hESC-DC immunotherapy platform."

Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said: "Recent advances in cancer immunotherapy have demonstrated the exciting potential of these treatments to improve outcomes in devastating diseases such as lung cancer. Better treatment options for lung cancer are badly needed and it is through collaborations such as this that we can save more lives sooner."