Home » Archive by Category

News

San Diego biotech news from BioSpace, Xconomy, PR Newswire, Marketwired and other sources, click on headlines to read the full story.

Chemical Disguise Transforms RNAi Drug Delivery

November 17, 2014 – 9:00 am | Edit Post

Researchers at University of California, San Diego School of Medicine have developed a way to chemically disguise RNAi drugs so that they are able to enter cells. Once inside, cellular machinery converts these disguised drug precursors — called siRNNs — into active RNAi drugs.

Solstice Biologics Announces Publication in Nature Biotechnology of Key RNAi Delivery Technology Licensed from UCSD

November 17, 2014 – 9:00 am | Edit Post

SAN DIEGO, Nov. 17, 2014 /PRNewswire/ – Solstice Biologics, a company focused on the targeted delivery of nucleic acid therapeutics, today announced the publication of data demonstrating an important advance in the critical hurdle of delivering ribonucleic acid interference (RNAi) therapeutics. The study, performed by Solstice co-founder, Steven F. Dowdy, Ph.D., professor in the Department of Cellular and Molecular Medicine at University of California, San Diego (UCSD), was published in the journal Nature Biotechnology and details a novel synthetic approach that disguises RNAi drugs and thereby significantly improves delivery into cells. Once inside targeted cells, the RNAi molecule is unmasked and disrupts specific biological pathways responsible for disease. The technology served as the starting point for Solstice’s RNAi delivery technology.

RNAi therapeutics represents a promising area of pharmaceutical research for their ability to block the production of proteins implicated in disease. However, RNAi-based drugs have numerous charged phosphate groups that not only prevent efficient transport into cells, but are also prone to degradation by nucleases. Although recent improvements in delivery have led to multiple liver specific clinical trials, unfortunately those approaches cannot be extended to RNAi delivery in other tissues beyond the liver. Consequently, RNAi delivery remains the critical hurdle for the field.

The breakthrough research described in this article was led by Dowdy and the research was funded by the W.M. Keck Foundation, U.S. Department of Defense, Leukemia & Lymphoma Society, Pardee Foundation and Howard Hughes Medical Institute. Solstice has an exclusive licensing agreement with UCSD for all intellectual property related to this discovery.

“This work from the lab of Solstice’s scientific co-founder set the foundation for important advances that Solstice has made in the last 18 months. It is exciting to see this tour de force study get the peer reviewed recognition it deserves,” said Lou Tartaglia, Ph.D., Solstice president and chief executive officer.

Dowdy and his team added neutral phosphotriester groups that mask the problematic phosphate charges on RNAi drugs. However, once inside the cell, enzymes cleaved the neutral phosphotriester groups to expose a charged and active RNAi molecule that shut down production of the target disease protein. Such a drug that is converted to its active form by a normal metabolic process is referred to as a prodrug. “While my lab at UCSD spent eight years laying down the foundation for phosphotriester modified RNAi molecules, Solstice has taken the technology to a whole new level,” said Dowdy.

“The general principles described in this study served as a critical starting point for Solstice to rapidly develop more advanced generations of the technology with unique pharmaceutical properties,” said Curt Bradshaw, Ph.D., Solstice co-founder and chief scientific officer. Building on the Dowdy lab’s work, the Solstice team altered the mechanism of prodrug release and introduced important new structural features. These next generation improvements have enhanced key performance characteristics such as deliverability, potency, stability and ease of synthesis. “Our most recent advances are now being directed to deliver nucleic acid therapeutics to non-liver tissues,” added Bradshaw.

The paper entitled, “Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications,” is available via Advance Online Publication on Nature Biotechnology’s website at: http://dx.doi.org/10.1038/nbt.3078

About Solstice Biologics

Solstice Biologics is a private company focused on solving the problem of targeting and delivery of nucleic acid therapeutics. The company is developing RNAi therapeutics that can enter different cell types and deliver on the promise of nucleic acid-based therapeutics. Solstice is backed by venBio and Aeris Capital AG. Visit www.solsticebio.com for more information.

Company Contact:Kristen Davisinfo@solsticebio.com

Media Contact:Jason SparkCanales Communications jason@canalecomm.com 619-849-6005
SOURCE Solstice Biologics

Mast Therapeutics To Present MST-188 Data At 2014 American Society Of Hematology Conference

November 17, 2014 – 6:00 am | Edit Post

SAN DIEGO, Nov. 17, 2014 /PRNewswire/ – Mast Therapeutics, Inc. (NYSE MKT: MSTX), a clinical-stage biopharmaceutical company, today announced that it will be presenting data from an ex vivo study of MST-188 (vepoloxamer), its lead product candidate, at the 56th Annual Meeting of the American Society of Hematology (ASH) taking place December 6 – 9, 2014 in San Francisco, California. The abstract entitled “Pro-coagulant Actions of Circulating Microparticles in Sickle Cell Anemia and Sepsis Associated Coagulopathy and their Modulation by a Triblock Polymer MST-188,” will be presented as part of the Oral and Poster Abstracts Program on Sunday December 7, 2014 in Session 321: Blood Coagulation and Fibrinolytic Factors: Poster II, from 6:00-8:00pm PST in the Moscone Center, West Building, Level 1. In addition, the abstract has also been published in the November 14, 2014 supplemental volume of the journal Blood.

In the ex vivo study, which was conducted at Loyola University Medical Center, the supplementation of MST-188 to blood samples collected from healthy normal individuals, sickle cell anemia (SCA) patients and sepsis associated coagulopathy (SAC) patients resulted in significant decrease in thrombin generation and marked decrease of functioning microparticles. The decrease in thrombin generation with MST-188 supplementation ranged from 24-55%. Thrombin is an enzyme that controls the conversion of fibrinogen to fibrin, which promotes blood clotting. Circulating microparticles (MPs) represent vesicles and cellular fragments generated in microvascular angiopathic conditions which facilitate pro-coagulant actions and contribute to thrombin generation and associated inflammatory processes. MST-188 is a triblock polymer with affinity to hydrophobic surfaces which are generated in microangiopathic conditions and may also interact with the phospholipid component of MPs. To test the hypothesis that MST-188 may decrease the pro-coagulant effects of MPs, a functional method to access MPs levels and a thrombin generation assay was used.

Martin Emanuele, Ph.D., Senior Vice President, Development, said: “These results suggest that MST-188 (vepoloxamer) antagonizes the procoagulant properties of microparticles formed in sepsis and during sickle cell crisis. This is important because dysfunctional coagulation is a key part of the pathology underlying ‘sludged’ blood flow (especially in the microcirculation) in both conditions.”

Abstract Information:

The abstract entitled “Pro-coagulant Actions of Circulating Microparticles in Sickle Cell Anemia and Sepsis Associated Coagulopathy and their Modulation by a Triblock Polymer MST-188″ will be presented by Jaweed Fareed, Ph.D., Professor of Pathology and Pharmacology at Loyola University Stritch School of Medicine;
The abstract is available on the Company’s website at http://www.masttherapeutics.com/technology/publications/.About Mast Therapeutics Mast Therapeutics, Inc. is a publicly traded biopharmaceutical company headquartered in San Diego, California.  The Company is leveraging the MAST (Molecular Adhesion and Sealant Technology) platform, derived from over two decades of clinical, nonclinical and manufacturing experience with purified and non-purified poloxamers, to develop MST-188, its lead product candidate, for serious or life-threatening diseases and conditions typically characterized by impaired microvascular blood flow and damaged cell membranes. 

The Company is enrolling subjects in EPIC, a pivotal Phase 3 study of MST-188 in sickle cell disease, and in a Phase 2 study to evaluate whether MST-188 improves the effectiveness of recombinant tissue plasminogen activator therapy in patients with acute limb ischemia.  The Company also is planning to initiate a Phase 2 clinical study of MST-188 in patients with acute decompensated heart failure in the first half of 2015. More information can be found on the Company’s web site at www.masttherapeutics.com. (Twitter: @MastThera) 

Mast Therapeutics™ and the corporate logo are trademarks of Mast Therapeutics, Inc.

Forward Looking Statements Mast Therapeutics cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements that are based on the Company’s current expectations and assumptions. Such forward-looking statements include, but are not limited to, statements relating to prospects for successful development of the Company’s product candidates, including MST-188 in sickle cell disease, and anticipated timing of achievement of development milestones, including commencement of clinical studies. Among the factors that could cause or contribute to material differences between the Company’s actual results and the expectations indicated by the forward-looking statements are risks and uncertainties that include, but are not limited to: the uncertainty of outcomes in ongoing and future studies of the Company’s product candidates and the risk that its product candidates, including MST-188, may not demonstrate adequate safety, efficacy or tolerability in one or more such studies, including EPIC; delays in the commencement or completion of clinical studies, including as a result of difficulties in obtaining regulatory agency agreement on clinical development plans or clinical study design, opening trial sites, enrolling study subjects, manufacturing sufficient quantities of clinical trial material, being subject to a “clinical hold,” and/or suspension or termination of a clinical study, including due to patient safety concerns or lack of funding; the potential for institutional review boards or the FDA or other regulatory agencies to require additional nonclinical or clinical studies prior to initiation of a planned clinical study of a product candidate; the risk that, even if clinical studies are successful, the FDA or other regulatory agencies may determine they are not sufficient to support a new drug application; the potential that, even if clinical studies of a product candidate in one indication are successful, clinical studies in another indication may not be successful; the Company’s reliance on contract research organizations (CROs), contract manufacturing organizations (CMOs), and other third parties to assist in the conduct of important aspects of development of its product candidates, including clinical studies, manufacturing, and regulatory activities for its product candidates, and that such third parties may fail to perform as expected; the Company’s ability to obtain additional funding on a timely basis or on acceptable terms, or at all; the potential for the Company to delay, reduce or discontinue current and/or planned development activities, including clinical studies, partner its product candidates at inopportune times or pursue less expensive but higher-risk and/or lower return development paths if it is unable to raise sufficient additional capital as needed; the risk that, even if the Company successfully develops a product candidate in one or more indications, it may not realize commercial success with its products and may never generate revenue sufficient to achieve profitability; the risk that the Company is not able to adequately protect its intellectual property rights relating to the MAST platform and MST-188 or AIR001 and prevent competitors from duplicating or developing equivalent versions of its product candidates; and other risks and uncertainties more fully described in the Company’s press releases and periodic filings with the Securities and Exchange Commission. The Company’s public filings with the Securities and Exchange Commission are available at www.sec.gov.

You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date when made. Mast Therapeutics does not intend to revise or update any forward-looking statement set forth in this press release to reflect events or circumstances arising after the date hereof, except as may be required by law.

Logo – http://photos.prnewswire.com/prnh/20120612/LA22456LOGO-a
SOURCE Mast Therapeutics, Inc.

David Hung, MD of Medivation Named EY Entrepreneur Of The Year™ 2014 National Life Sciences Award Winner

November 17, 2014 – 6:00 am | Edit Post

SAN FRANCISCO, Nov. 17, 2014 /PRNewswire/ – David Hung, MD, the founder, President and CEO of Medivation, has been named the EY Entrepreneur Of The Year™ 2014 National Life Sciences Award winner.

The EY Entrepreneur Of The Year Award, a leading business award for entrepreneurs, encourages entrepreneurial activity and recognizes leaders and visionaries who demonstrate innovation, financial success and personal commitment as they create and build world-class businesses.

Hung was recognized for developing visionary technologies and delivering unprecedented results in the biotech field. He was honored at the Entrepreneur Of The Year Awards gala, the culminating event of the EY Strategic Growth Forum® in Palm Springs, Calif. The Forum is the nation’s premier gathering of high-growth, market-leading companies. Awards were given in 10 additional categories.

The EY Entrepreneur Of The Year Award winners were selected by an independent panel of judges and from more than 250 regional award recipients. 

“Dr. David Hung’s passion and pledge to bringing groundbreaking solutions for the world’s toughest diseases and illnesses in a truly innovative way speaks for itself,” said Mike Kacsmar, EY Entrepreneur Of The Year Americas Program Director.  “He leads one of the most visionary biopharmaceutical companies in the world, and we couldn’t be more pleased to credit him with this honor.”

Passion from the startHung realized that he was limited in the number of people he could help in academic medicine. With the unending desire to do more, he left academic medicine for the business world. Prior to Medivation, Hung started another company, Pro-Duct Health, which was also highly successful, turning $22 million of VC funding into $168 million through an acquisition.

As the largest biotech employer in downtown San Francisco, Medivation has achieved great success in identifying drugs that fight and even cure difficult diseases such as breast and prostate cancer, as well as Alzheimer’s.

A comeback story worth noting Despite achieving immense growth and success, that wasn’t always the storyline for Medivation. The company nearly went bankrupt after a failed late-stage drug trial. Fast-forward to now, the company is leading the industry by developing revolutionary technologies and overcoming clinical development time limitations to prolong and ultimately save lives.

One such example of this is the company’s breakthrough drug, Xtandi. Generally, it takes 17 years and $800 million from laboratory bench to FDA approval for a drug in the pharma industry. Hung and his team successfully managed to receive approval on Xtandi in just seven years. What’s more, the drug was then made available to patients in only two weeks, setting yet another industry benchmark.

Today, Medivation has evolved into a global company, employing over 80 chemists in India and more than 20 biologists in Chile, in addition to the hundreds of development employees in San Francisco.

EY Entrepreneur Of The Year 2014 National Life Sciences finalists: In addition to Hung, the EY Entrepreneur Of The Year Life Sciences national finalists in the US were: Kevin T. Conroy, President and CEO of Exact Sciences Corporation, based in Madison, Wis.; Ted Schroeder, President and CEO of Cadence Pharmaceuticals, based in San Diego, Calif.; and Dale Wollschleger, President and CEO of ExactCare Pharmacy, based in Valley View, Ohio.

EY Entrepreneur Of The YearTM 2014 National Overall Award winnerDr. David Hung of Medivation was also named the EY Entrepreneur Of The YearTM 2014 National Overall Award winner.

Video and photosTo view photos of all of the Entrepreneur Of The Year winners, please visit ey.com/us/eoy.

SponsorsFounded and produced by Ernst & Young LLP, the Entrepreneur Of The Year Awards are nationally sponsored in the US by SAP America and the Ewing Marion Kauffman Foundation.

About EY Entrepreneur Of The Year™EY Entrepreneur Of The Year is the world’s most prestigious business award for entrepreneurs. The program makes a difference through the way it encourages entrepreneurial activity among those with potential and recognizes the contribution of people who inspire others with their vision, leadership and achievement. As the first and only truly global awards program of its kind, Entrepreneur Of The Year celebrates those who are building and leading successful, growing and dynamic businesses, recognizing them through regional, national and global awards programs in more than 145 cities in more than 60 countries. ey.com/eoy

About EY’s Strategic Growth Markets NetworkEY’s worldwide Strategic Growth Markets Network is dedicated to serving the changing needs of high-growth companies. For more than 30 years, we’ve helped many of the world’s most dynamic and ambitious companies grow into market leaders. Whether working with international mid-cap companies or early stage, venture-backed businesses, our professionals draw upon their extensive experience, insight and global resources to help your business succeed. For more information, please visit us at ey.com/sgm or follow news on Twitter @EY_Growth.

About EY EY is a global leader in assurance, tax, transaction and advisory services. The insights and quality services we deliver help build trust and confidence in the capital markets and in economies the world over. We develop outstanding leaders who team to deliver on our promises to all of our stakeholders. In so doing, we play a critical role in building a better working world for our people, for our clients and for our communities.

EY refers to the global organization, and may refer to one or more, of the member firms of Ernst & Young Global Limited, each of which is a separate legal entity. Ernst & Young Global Limited, a UK company limited by guarantee, does not provide services to clients. For more information about our organization, please visit ey.com.

This news release has been issued by Ernst & Young LLP, an EY member firm serving clients in the US.

Logo – http://photos.prnewswire.com/prnh/20130701/NY40565LOGO-b
SOURCE EY

Dr. David Hung, founder, President and CEO of Medivation, named EY Entrepreneur Of The Year™ 2014 National Overall Award winner

November 17, 2014 – 6:00 am | Edit Post

SAN FRANCISCO, Nov. 17, 2014 /PRNewswire/ – Dr. David Hung, MD, founder, President and CEO of Medivation, a biopharmaceutical company focused on the rapid development of therapies to treat cancer and neurodegenerative diseases, has been named the EY Entrepreneur Of The Year™ 2014 National Overall Award winner. The EY Entrepreneur Of The Year Award, a leading business award for entrepreneurs, encourages entrepreneurial activity and recognizes leaders and visionaries who demonstrate innovation, financial success and personal commitment as they create and build world-class businesses.

Hung was chosen for his inspiring work creating Medivation, which identifies, in-licenses and develops visionary technology for life-threatening diseases, as well as the urgency with which he’s tackling these illnesses. Medivation acquires early-development stage pharmaceuticals and medical devices that have promising clinical, intellectual property and commercial prospects, and then identifies and executes the strategic pathway that will allow the most rapid, efficient and effective development of these products. Hung was honored at the EY Entrepreneur Of The Year Awards gala, the culminating event of the EY Strategic Growth Forum® in Palm Springs, Calif. The Forum is the nation’s premier gathering of high-growth, market-leading companies. Awards were given in 10 additional categories.

The EY Entrepreneur Of The Year Award winners were selected by an independent panel of judges and from more than 250 regional award recipients.

“Entrepreneurship is all about thinking outside of the box to develop solutions to everyday problems,” said Mike Kacsmar, EY Entrepreneur Of The Year Americas Program Director.  “Dr. David Hung recognizes that when a patient is critically ill, time is all that matters. Medivation challenges clinical development time limitations, and as a result, the company has been able help prolong and save lives by making an unprecedented shift to the industry benchmark of how long it takes to bring life-saving products to market.”

A change to do more leads to successA graduate of Harvard University and the University of California, San Francisco Medical School, Hung is a hematologist, oncologist and scientist. His early work with patients had a profound effect on him, and this experience made him understand that while he was passionate about treating patients as a doctor, he was limited in the number that he could reach. He felt compelled to help more. Hung realized he could affect millions of people by developing new, revolutionary technology, and with that goal in mind, he made the tough decision to leave academic medicine for industry.

His gamble was a success. He founded Medivation in 2003 with a $1 million bridge loan and took the company public through a reverse merger in 2004. Today the company is one of the biotech industry’s greatest success stories.  Additionally, Hung has richly rewarded those that invested in Medivation at its origin – from its original capital raise in 2003, the share price has seen a 100 fold return for those investors.

A matter of timeThe true motivation behind Medivation’s success is the urgency and care it puts into developing treatments and technologies for those who need it most. While Hung’s employees each have separate skills and practices, they all work with a sense of commitment and urgency. Hung knows, when you’re dealing with terminally ill patients, time is critical.

It is with this understanding that Hung has positioned Medivation to challenge the biotech industry to successfully identify drugs that fight and even cure the most difficult diseases such as breast and prostate cancer, as well as Alzheimer’s. Hung is passionate about the difficult diseases, and he has not only created novel treatments, but done so more quickly than traditionally perceived possible.

An example of this commitment is also one of Medivation’s greatest successes: its breakthrough drug, Xtandi. In the pharmaceutical industry, it generally takes 17 years and $800 million from laboratory bench to FDA approval for a drug. Hung motivated his team and successfully managed the approval of Xtandi – from idea to use – in only seven years. This record-breaking feat was made possible with total capital of only $175 million raised over 10 years. The product was then made available to patients in only two weeks, again setting an unprecedented industry benchmark.

Putting people firstMedivation is the largest biotech employer in downtown San Francisco. From day one during orientation, all 400 employees are instilled with the importance of innovative thinking. This collective mindset allows the company to employ new approaches to old diseases, and this way of doing things has often led to revolutionary results.

Hung understands the importance of leading by example and works side-by-side with his teams. He sends a monthly note to his employees, emphasizing a refusal to accept no for an answer. He often challenges them to think about if their life depended on it – would the answer still be no?

Video and photosTo view photos of all of the EY Entrepreneur Of The Year winners, please visit ey.com/us/eoy.

SponsorsFounded and produced by Ernst & Young, the Entrepreneur Of The Year Awards are nationally sponsored in the US by SAP America and the Ewing Marion Kauffman Foundation.

 

About EY Entrepreneur Of The Year™EY Entrepreneur Of The Year is the world’s most prestigious business award for entrepreneurs. The program makes a difference through the way it encourages entrepreneurial activity among those with potential and recognizes the contribution of people who inspire others with their vision, leadership and achievement. As the first and only truly global awards program of its kind, Entrepreneur Of The Year celebrates those who are building and leading successful, growing and dynamic businesses, recognizing them through regional, national and global awards programs in more than 145 cities in more than 60 countries. ey.com/eoy

About EY’s Strategic Growth Markets NetworkEY’s worldwide Strategic Growth Markets Network is dedicated to serving the changing needs of high-growth companies. For more than 30 years, we’ve helped many of the world’s most dynamic and ambitious companies grow into market leaders. Whether working with international mid-cap companies or early stage, venture-backed businesses, our professionals draw upon their extensive experience, insight and global resources to help your business succeed. For more information, please visit us at ey.com/sgm or follow news on Twitter @EY_Growth.

About EY EY is a global leader in assurance, tax, transaction and advisory services. The insights and quality services we deliver help build trust and confidence in the capital markets and in economies the world over. We develop outstanding leaders who team to deliver on our promises to all of our stakeholders. In so doing, we play a critical role in building a better working world for our people, for our clients and for our communities.

EY refers to the global organization, and may refer to one or more, of the member firms of Ernst & Young Global Limited, each of which is a separate legal entity. Ernst & Young Global Limited, a UK company limited by guarantee, does not provide services to clients. For more information about our organization, please visit ey.com.

This news release has been issued by Ernst & Young LLP, an EY member firm serving clients in the US.

Logo – http://photos.prnewswire.com/prnh/20130701/NY40565LOGO-b
SOURCE EY

DelMar Pharmaceuticals’ Promising New Data Support the Potential of VAL-083 to Meet Significant Unmet Medical Needs in the Treatment of Glioblastoma Multiforme

November 17, 2014 – 6:00 am | Edit Post

VANCOUVER, British Columbia, MENLO PARK, Calif., and MIAMI, Nov. 17, 2014 /PRNewswire/ – DelMar Pharmaceuticals, Inc. (OTCQB: DMPI) (“DelMar” and “DelMar Pharma”) today announced the presentation of new data supporting the development of VAL-083 (dianhydrogalactitol), which is currently undergoing clinical development in the United States as a potential new chemotherapy for the treatment of refractory glioblastoma multiforme (GBM), the most common and deadly form of human brain cancer.

The data were presented in two additional abstracts on Friday November 14, 2014 during the evening scientific session at the Society for NeuroOncology Annual Meeting. Overall, DelMar presented three abstracts at the meeting. 

On Friday, DelMar announced the presentation of an abstract entitled In vivo efficacy of VAL-083 in the treatment of MGMT-positive glioblastoma multiforme (GBM), which highlighted the company’s research into the activity of VAL-083 in comparison to standard-of-care temozolomide in animal models of GBM.

The presentation can be viewed at:  DELMAR INVIVO DATA PRESENTATION SNO2014

The second abstract entitled VAL-083 is a novel N7 alkylating agent that inhibits the growth of glioma stem and non-stem cultures, including temozolomide-resistant lines presented by DelMar’s collaborators from the University of California San Francisco (UCSF), provided further pre-clinical validation of VAL-083′s different and potentially superior activity compared to standard-of-care temozolomide. 

The presentation can be viewed at:  DELMAR INVITRO DATA PRESENTATION SNO2014

The third abstract entitled Phase I/II study of dianhydrogalactitol (VAL-083) in patients with recurrent malignant glioblastoma multiforme (GBM) provided an update on DelMar’s ongoing Phase I/II clinical trial with VAL-083 in the treatment of refractory glioblastoma. 

The presentation can be viewed at:  DELMAR CLINCAL PRESENTATION SNO2014

Overview of UCSF in vitro Research Findings

“Researchers from UCSF previously demonstrated that the response of both cancer stem cells (CSC) and paired non-CSC cultures isolated from glioblastoma patients to temozolomide, the current standard of care in the treatment of glioblastoma was dependent on the presence or absence of an enzyme called O6-methylguanine methyltransferase (MGMT),” said Jeffrey Bacha, president & CEO of DelMar Pharmaceuticals.  “We collaborated with UCSF to investigate how the same cultures respond to VAL-083 alone or in combination with radiation, and how the response would compare to temozolomide.”

GBM is the most common and deadly form of human brain cancer.  The standard of care for newly diagnosed GBM patients is surgical resection followed by temozolomide and radiation and subsequent maintenance therapy with temozolomide alone. Temozolomide is effective for a minority of patients that low expression of MGMT, a DNA repair enzyme that repairs the cytotoxic damage temozolomide causes to cancer cells.  The majority of patients exhibit high expression of MGMT and are resistant to temozolomide.

“VAL-083 is a first-in-class alkylating agent that crosses the blood brain barrier and is currently in clinical trials for glioma patients with recurrent GBM.  We hypothesized that the N7 alkylating agent, VAL-083, is not subject to MGMT mediated repair and might therefore be a more potent chemotherapeutic for the treatment of GBM,” said Joseph Costello, Professor of Neurological Surgery at UCSF.

Patient derived GBM cells were treated with increasing doses of temozolomide or VAL-083 and cell cycle analysis was performed four days after treatment.  VAL-083 proved to be effective against temozolomide resistant cultures, even at single micromolar (uM) doses. 

The activity of VAL-083 and temozolomide were compared by treating CSCs with a 5uM dose of VAL-083 or a 50uM dose of temozolomide in combination with a standard 2 gray (Gy) dose of radiation.  CSCs were examined for cell viability four (4) days post treatment.  The cultures studied were not sensitive to the combination of temozolomide and radiation but were sensitive to treatment with the combination of VAL-083 and radiation.  Further, VAL-083 was shown to increase cancer cells sensitivity to radiation at doses below 2uM.

In summary, UCSF researchers demonstrated that:

VAL-083 appears to cause cell cycle arrest and loss of cell viability at lower concentrations than temozolomide;
Unlike temozolomide, VAL-083 is active against stem and non-stem cells and its activity affected by MGMT status. All cultures tested were sensitive to VAL-083 exposure; and
For all cultures tested, a potential additive effect of VAL-083 with radiation therapy was observed, particularly at low concentrations of VAL-083.”These in vitro results suggest that VAL-083 may provide greater killing of MGMT unmethylated tumor cells compared to the standard-of-care chemotherapy,” added Prof. Costello.

Mr. Bacha added, “While this program is progressing in clinical trials for GBM patients having failed approved therapies we continue believe in the importance of nonclinical research to differentiate VAL-083 not only for continued validation of its promise as a potential treatment for refractory GBM, but also to support its potential as an alternative front-line chemotherapy in the future.”

Overview of Clinical Data Presentation:

To date, 13 male and 10 female subjects with GBM have completed safety analysis at doses up to 40mg/m2 in DelMar’s VAL-083 clinical trial without encountering dose limiting toxicity (DLT).  Seven additional subjects with CNS metastases were enrolled at lower doses; however, enrollment at doses above 5mg/m2 has been limited to GBM.

Historical studies sponsored by the US National Cancer Institutes (NCI) achieved promising results in newly diagnosed and recurrent GBM using a dosing regimen of 25 mg/m2/day for five days every five weeks.  Historically, dose limiting hematologic toxic effects were noted on white blood cell (WBC) and platelet counts.  For example, Egan etal. (1979) observed nadir of 2,100/mL (lymphopenia) and 88,000/mL (thrombocytopenia), respectively.  In a separate study, a dose of 40mg/m2/day for five days resulted in a median platelet nadir of 31,000/mL and WBC nadir of 2,300/mL.  In general, nadir occurred within three weeks and returned to normal within seven (7) days.  Anemia, nausea and vomiting were usually mild to moderate.  No renal, hepatic, central nervous system, cardiac, or pulmonary toxicity was identified.

The DelMar dosing regimen uses a cycle of treatment on the first three days of every three weeks.  “We hypothesized that this regimen along with improvement in management of myelosuppression in the modern era would allow for more aggressive dosing and potentially improved patient outcomes,” said Mr. Bacha.

A summary of recent, ongoing and planned dose cohorts compared to the historical regimen used in NCI-sponsored Phase II GBM studies is presented in the table below:

DOSING REGIMEN & STUDY

SINGLE DOSE

Acute Regimen

(single cycle)

Comparative Cumulative Dose

(@ 35 days)

Dose Density (dose per week)

Status

NCI GBM historical regimen

(Eagan etal)

daily x 5 q 5wks

(cycle = 35 days)

25 mg/m2

x5 days =

125 mg/m2

125 mg/m2

25mg/m2/wk

Historical Studies:

Myelosuppression observed

DelMar VAL-083 regimen

daily x 3 q 3wks

(cycle = 21 days)

30 mg/m2

x3 days =

90 mg/m2

180 mg/m2

30mg/m2/wk

No DLT

40 mg/m2

120 mg/m2

240 mg/m2

40mg/m2/wk

No DLT

50 mg/m2

150 mg/m2

300 mg/m2

50mg/m2/wk

ongoing

60 mg/m2

180 mg/m2

360 mg/m2

60mg/m2/wk

planned

“We have now achieved significantly higher doses in comparison to the NCI regimen without encountering dose limiting toxicity,” confirmed Mr. Bacha.

Safety Data Summary

DelMar reported that NCI-CTCAE Grade 1 lymphopenia (LLN to >3,000/mL) and thrombocytopenia (platelet counts LLN to >75,000/mL) at doses above 20mg/m2/day x 3 days had been observed in GBM treated to date in the current study; however, no serious adverse events related to study drug or dose limiting toxicity (DLT) has been encountered at doses up to 40mg/m2/day x 3 days.

A summary of hematologic-related safety data observed to date in the DelMar clinical trial is presented in the table below:

Cohort

Dose &

Hematologic Toxicity

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Total

1 – 4

up to 10 mg/m2

LYMPHOPENIA

0

0

0

0

0

0

THROMBOCYTOPENIA

0

0

0

0

0

0

5

20 mg/m2

LYMPHOPENIA

1 (25%)

0

0

0

0

1 (25%)

THROMBOCYTOPENIA

0

0

0

0

0

0

6

30 mg/m2

LYMPHOPENIA

0

0

0

0

0

0

THROMBOCYTOPENIA

1 (33%)

0

0

0

0

1 (25%)

7

40 mg/m2

LYMPHOPENIA

1 (33%)

0

0

0

0

1 (25%)

THROMBOCYTOPENIA

0

0

0

0

0

0

8

50 mg/m2

Ongoing

9

60 mg/m2

TBD if no DLT @ 50mg/m2

Mr. Bacha stated, “While low-grade thrombocytopenia and lymphopenia may signal that we are approaching the maximum tolerated dose, we believe that maximizing drug exposure and concentration at the tumor through exploration of higher doses will enhance patient outcomes.” 

“We are pleased that our modernized regimen is allowing us to achieve the goal to ‘hit the tumor harder more often.’ Based on the results to date, we filed a protocol amendment with the FDA and continued dose escalation under our protocol to 50mg/m2.” 

In accordance with the protocol, maximum tolerated dose (MTD) will be established by dose limiting toxicity (DLT), defined as:

Hematologic DLT
Grade 4 thrombocytopenia (platelets <25,000/mL), or Grade 3 thrombocytopenia (platelets <50,000 -25,000/mL with hemorrhage);
Absolute neutrophil count (ANC) nadir < 500/mL or platelet count <50,000/mL, either lasting for more than five days; 
ANC < 500/mL with fever (febrile neutropenia); or
Treatment delays of greater than 3 weeks for hematologic toxicity
Non-hematologic DLT
Any grade 3 or 4 non-hematologic toxicity due to treatment with the exception of alopecia, nausea, and vomiting;
Grade 3 or 4 nausea or vomiting while receiving an optimal antiemetic regimen for prophylaxis and management;
Treatment delays of greater than 3 weeks for toxicityPharmacokinetic Summary:

DelMar also reported updated pharmacokinetic analyses for cohorts 1-7, which demonstrate dose-dependent linear systemic exposure with a short plasma 1-2 h terminal half-life; Cmax at the highest dose tested (cohort 7, 40 mg/m2) ranged from 1130 to 739 ng/mL (7.7 to 5.1 uM).  These data are correlated with the PK profile published in the scientific literature (Eagan et al 1982) as shown in the following figure:

“One of the many benefits of the depth NCI-sponsored clinical trial data available to us is the opportunity to correlate our modern data with historical pharmacokinetics,” said Mr. Bacha.  “By extrapolating central nervous system (CNS) drug exposure from information in the published literature, we can calculate the expected CNS concentrations based on observed plasma concentrations of VAL-083 in our clinical trial.” 

DelMar reported that plasma drug concentrations predict that levels of VAL-083 in brain tissue exceed levels that have been shown to be effective against GBM cell lines in vitro. 

“In other words, while we have not reached the maximum tolerated dose, the drug levels reaching the tumor already are predicted to exceed those shown to be effective in laboratory studies,” added Mr. Bacha.

The following table illustrates the estimated concentration in of VAL-083 Human Brain tissue in the 40mg/m2 dose cohort compared to the concentration required for activity against GBM cell lines (IC50) in laboratory studies. 

Dose:

Each Day of Cycle in Current Trial

Plasma Cmax

(ug/mL)1

Estimated Maximum Tumor Concentration in Brain 2,3

IC50 in

GBM Cell Lines

(ug/g tissue)

uM*

uM

40mg/m2 Day-1

0.781

0.344

2.36

2.5-5.0

40mg/m2 Day-2

0.781

0.503

3.45

2.5-5.0

40mg/m2 Day-3

0.781

0.563

3.86

2.5-5.0

Anti-tumor Activity and Next Steps

The goal of DelMar’s Phase I/II trial is to establish the maximum tolerated dose (MTD) of VAL-083 in a modernized dosing regimen for advancement into registration directed trials as a potential new therapy for the treatment of refractory GBM. 

Patients enrolled have recurrent GBM that has failed to respond to prior therapy.  Cycle 1 toxicity is measured for determination of MTD.  Tumor volume is measured via Response Assessment in Neuro-Oncology (RANO) criteria prior to every other 21-day treatment cycle and patients exhibiting stable disease or tumor regression allowed to remain on study drug.   Three patients exhibiting a response (stable disease or partial response) reported improved clinical signs with a maximum response of 28 cycles (84 weeks) prior to discontinuing due to adverse events unrelated to the study. 

To date, no drug-related serious adverse events have been detected and MTD has not been reached at doses up to 40mg/m2.  DelMar is currently studying a dose of 50mg/m2 in this clinical trial.  The current clinical protocol requires acquisition of safety data for 35 days following initial treatment with VAL-083 in three patients to meet the primary endpoint for determination of MTD.  While patients have been identified for the 50 mg/m2 cohort, none have yet completed the required 35 day follow-up period.  Normal instances in clinical development such as patient ineligibility at screening, failure to obtain patient consent or patient death prior to 35 days following dosing may require identification and recruitment of replacement patients.  Once 35-day safety data from three patients in the 50mg/m2 cohort is obtained, review of data will either confirm MTD or allow advancement to higher doses. 

“We will work with our clinical advisors to obtain and analyze these data in the timeliest manner possible,” said Mr. Bacha.  “Based on our current enrollment and timelines, we believe we remain on track to advance to registration directed trials with VAL-083 in the first half of 2015.”

About VAL-083

VAL-083 is a first-in-class, small-molecule chemotherapeutic with a unique mechanism of action. In more than 40 Phase 1 and 2 clinical studies sponsored by the National Cancer Institute, VAL-083 has shown safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.  As a potential treatment for glioblastoma, VAL-083′s mechanism of action is unaffected by the expression of MGMT, a DNA repair enzyme that causes chemotherapy resistance to front-line treatment with Temodar® (temozolomide).  DelMar is currently studying VAL-083 in a Phase 1/2 clinical trial for patients with refractory glioblastoma multiforme. 

About Glioblastoma Multiforme (GBM)

Glioblastoma multiforme (GBM) is the most common and most malignant form of brain cancer. Approximately 15,000 people are diagnosed with GBM each year in the U.S., with similar incidence in Europe. Standard of care is surgery, followed by either radiation therapy, or radiation therapy combined with temozolomide. Approximately 60 percent of GBM patients treated with temozolomide experience tumor progression within one year. More than half of glioblastoma patients will fail the currently approved therapies and face a very poor prognosis.

About the Society for Neuro-Oncology (SNO) annual meeting

The Society for Neuro-Oncology is a multidisciplinary organization dedicated to promoting advances in neuro-oncology through research and education. It is the premier North American organization for clinicians, basic scientists, nurses and other health care professionals whose focus is central nervous system tumors in children and adults. The 19th Annual Scientific Meeting and Education Day was held November 13-16, 2014, at the Loews Hotel South Beach in Miami.

About DelMar Pharmaceuticals, Inc.

DelMar Pharmaceuticals, Inc. was founded to develop and commercialize proven cancer therapies in new orphan drug indications where patients are failing or have become intolerable to modern targeted or biologic treatments. The Company’s lead drug in development, VAL-083, is currently undergoing clinical trials in the U.S. as a potential treatment for refractory glioblastoma multiforme. VAL-083 has been extensively studied by U.S. National Cancer Institute, and is currently approved for the treatment of chronic myelogenous leukemia (CML) and lung cancer in China. Published pre-clinical and clinical data suggest that VAL-083 may be active against a range of tumor types via a novel mechanism of action that could provide improved treatment options for patients.

For more information, please visit www.delmarpharma.com or follow us on Twitter @delmarpharma or Facebook.com/delmarpharma.

Safe Harbor Statement

Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on current expectations, but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company’s ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company’s products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and, the Company’s business, research, product development, regulatory approval, marketing and distribution plans and strategies. These and other factors are identified and described in more detail in our filings with the SEC, including, our current reports on Form 8-K. We do not undertake to update these forward-looking statements made by us.

Photo – http://photos.prnewswire.com/prnh/20141117/158912-INFO
SOURCE DelMar Pharmaceuticals, Inc.

Aptose Biosciences to Present at The Stifel 2014 Healthcare Conference

November 17, 2014 – 6:00 am | Edit Post

SAN DIEGO and TORONTO, Nov. 17, 2014 /PRNewswire/ – Aptose Biosciences Inc.
(NASDAQ: APTO, TSX: APS), a clinical-stage company developing new
therapeutics and molecular diagnostics that target the underlying
mechanisms of cancer, today announced that William G. Rice, Ph.D.,
Chairman, President and Chief Executive Officer, will present at the
upcoming Stifel 2014 Healthcare Conference on November 19, 2014, at
8:35 a.m. ET, at The New York Palace Hotel, New York. Dr. Rice will
provide a corporate overview of the Company’s recent activities and
strategic direction including plans to develop Aptose’s lead clinical
agent, APTO-253 for acute myeloid leukemia (AML), myelodysplastic
syndromes (MDS) and other hematologic malignancies.

A live audio webcast of the presentation will be accessible by visiting:

http://www.veracast.com/webcasts/stifel/healthcare2014/27213553963.cfm

The audio webcast will be archived shortly after the live event and will
be available for 90 days through the Aptose website at www.aptose.com.

About Aptose Biosciences

Aptose Biosciences is a clinical-stage biotechnology company committed
to discovering and developing personalized therapies that address unmet
medical needs in oncology.  Aptose is advancing new therapeutics
focused on novel cellular targets on the leading edge of cancer
research coupled with companion diagnostics to identify the optimal
patient population for its products.  Aptose’s lead anticancer agent
APTO-253 is under development for AML, MDS and other hematologic
malignancies.  For further information, please visit www.aptosebiosciences.com.

Forward Looking Statements

This press release contains forward-looking statements within the
meaning of Canadian and U.S. securities laws. Such statements include,
but are not limited to, statements relating to the Company’s plans,
objectives, expectations and intentions and other statements including
words such as “continue”, “expect”, “intend”, “will”, “should”,
“would”, “may”, and other similar expressions. Such statements reflect
our current views with respect to future events and are subject to
risks and uncertainties and are necessarily based upon a number of
estimates and assumptions that, while considered reasonable by us are
inherently subject to significant business, economic, competitive,
political and social uncertainties and contingencies. Many factors
could cause our actual results, performance or achievements to be
materially different from any future results, performance or
achievements described in this press release. Such expressed or implied
forward looking statements could include, among others: our ability to
obtain the capital required for research and operations; the inherent
risks in early stage drug development including demonstrating efficacy;
development time/cost and the regulatory approval process; the progress
of our clinical trials; our ability to find and enter into agreements
with potential partners; our ability to attract and retain key
personnel; changing market conditions; and other risks detailed from
time-to-time in our ongoing quarterly filings, annual information
forms, annual reports and annual filings with Canadian securities
regulators and the United States Securities and Exchange Commission.

Should one or more of these risks or uncertainties materialize, or
should the assumptions set out in the section entitled “Risk Factors”
in our filings with Canadian securities regulators and the United
States Securities and Exchange Commission underlying those
forward-looking statements prove incorrect, actual results may vary
materially from those described herein. These forward-looking
statements are made as of the date of this press release and we do not
intend, and do not assume any obligation, to update these
forward-looking statements, except as required by law. We cannot assure
you that such statements will prove to be accurate as actual results
and future events could differ materially from those anticipated in
such statements. Investors are cautioned that forward-looking
statements are not guarantees of future performance and accordingly
investors are cautioned not to put undue reliance on forward-looking
statements due to the inherent uncertainty therein.

SOURCE Aptose Biosciences Inc.

PDF available at: http://stream1.newswire.ca/media/2014/11/17/20141117_C9714_DOC_EN_43208.pdf

ClinMet Metabolomic Panel Shown To Reflect Renal Function Status, May Predict Drug Activity In Diabetic Kidney Disease

November 17, 2014 – 5:35 am | Edit Post

SAN DIEGO, Nov. 17, 2014 /PRNewswire/ – Further evidence that stimulating mitochondrial function results in improved markers of renal and cardiovascular dysfunction and that such markers, incorporated by ClinMet Inc. in a proprietary urine metabolomics profile, can help monitor renal function and predict response to drug therapies was presented over the weekend at Kidney Week 2014.

“Studies in both animals and humans have shown that reduced mitochondrial function appears to play a critical role in the progression of chronic kidney disease (CKD), as well as cardiovascular complications of diabetes. Moreover, findings suggest that drugs that restore mitochondrial superoxide levels can protect against further disease progression,” said ClinMet scientific founder, Kumar Sharma, M.D., F.A.H.A. Professor of Medicine and the Director of Center for Renal Translational Medicine and the Institute of Metabolomic Medicine at the University of California, San Diego. “This week we have presented further validation for a novel group of urine metabolites related to mitochondrial function that are reduced in diabetics with decreased renal function, but not in individuals without kidney disease. New clinical studies have now shown that novel drugs that may be effective in this population increase the reduced metabolite levels towards non-CKD levels, possibly reflecting a stabilization of mitochondrial function.”

A variety of oral and poster presentations by Dr. Sharma, ClinMet scientists and their academic collaborators and corporate partners were presented during the annual scientific meeting of the American Association of Nephrology, which was held from November 11 – 16 in Philadelphia, PA.

Dr. Sharma noted that the ClinMet metabolomics panel may provide the means for companies not only to stratify patients for clinical trials of potential therapeutics for diabetic kidney disease, but may also aid in related drug discovery by helping to predict the efficacy of potential therapeutics in this population. The new data is strongly supportive of this concept.

“Quantitative metabolomics studies offer a useful approach for more accurately understanding drug activity in the discovery and development of new therapies for diabetes and its related complications including kidney disease and cardiovascular conditions,” said Shoba Sharma, ClinMet co-founder and Chief Operating Officer. “ClinMet’s technological proficiency in metabolomics combined with our translational medicine expertise in the field of diabetes and kidney disease make our drug discovery platform and services unique in the industry.”

About ClinMet Inc.ClinMet Inc., founded in 2011, is a privately held company based in San Diego, CA that provides pharmaceutical companies with clinically relevant insights and actionable information about drug efficacy, safety and mechanism of action using its proprietary urine metabolomics biomarker platform for diabetes, kidney disease, obesity and cardiovascular disease. ClinMet applies its unique combination of in-depth clinical insights, proprietary metabolomics expertise, and computational know-how to improve the speed and success rate of drug development. The company helps drug developers to efficiently transform promising compounds into safe and effective medicines and to effectively develop and implement their companion diagnostics strategy.  For more information, please visit the ClinMet website at http://www.clinmet.com.

Logo - http://photos.prnewswire.com/prnh/20131009/MM95277LOGO
SOURCE ClinMet Inc.

Receptos Announces Proposed Underwritten Public Offering Of Common Stock

November 17, 2014 – 5:00 am | Edit Post

SAN DIEGO, Nov. 17, 2014 (GLOBE NEWSWIRE) — Receptos, Inc. (Nasdaq:RCPT), a biopharmaceutical company developing therapeutic candidates for the treatment of immune and metabolic diseases, announced today that it intends to offer shares of its common stock in an underwritten public offering. All of…

Ichor Medical Systems, Inc. Awarded Contract For Development Of TriGrid Platform For Passive Immunization

November 17, 2014 – 5:00 am | Edit Post

Ichor Medical Systems Awarded DARPA Contract for Development of TriGrid Platform for Passive ImmunizationSAN DIEGO–(BUSINESS WIRE)–Ichor Medical Systems (Ichor) of San Diego announced today that they have received a contract through the Defense Advanced Research Projects Agency (DARPA) and supported by the U.S. Army Research Office for up to …