Saladax Biomedical, Inc. announced that Myriad Genetics, Inc. (NASDAQ:MYGN) has developed and launched its seventh molecular diagnostic product, OnDoseTM. OnDose™, which utilizes patent rights licensed from Saladax. OnDose provides a quantitative measure in blood of exposure of the patient to 5-Fluorouracil (5-FU), providing oncologists with a routinely available tool for personalizing infusion chemotherapy drug dosing to help optimize clinical efficacy and reduce toxic side effects.

5-FU is the foundation for colorectal cancer infusion chemotherapy regimens, and is also used for treating head and neck and metastatic breast cancer. With drug clearance varying by as much as 30-fold among different individuals, the traditional Body Surface Area (BSA) dosing methods result drug concentrations in the blood that vary widely. Studies have demonstrated a correlation of 5-FU treatment efficacy with blood concentration over time (Area Under the Curve) rather than dose. However, oncologists have previously not had a convenient way of measuring blood levels and as a result, many patients were over-dosed and many more were under-dosed.

“The introduction of OnDose™ is a new and vitally important advance in cancer care,” said Dr. Edward Chu, M.D., Deputy Director of the Yale Cancer Center in New Haven, CT. “For the first time, a fast and accurate method of measuring and monitoring 5-FU blood levels will now be accessible to the practicing oncologist. OnDose™ will offer each oncologist who treats colorectal cancer patients an easy way to personalize their 5-FU regimen and help optimize their outcomes.”

Myriad obtained from Saladax an exclusive North American license of patents arising from pioneering discoveries by Saladax. Under the terms of the patent license, Myriad has exclusive rights to develop, manufacture, sell and distribute products developed by Myriad for 5-FU in the United States and Canada. OnDose is being sold through Myriad’s 150-person oncology sales force. Approximately 175,000 colorectal cancer patients are treated with 5-FU infusions annually in the United States. Myriad estimates that an average of eight OnDose measurements will occur during the full course of 5-FU infusion treatment and Myriad is offering the test for $300 per determination.

“We are very pleased that Myriad’s development of a test based on licensed rights from Saladax’s discoveries has resulted in a product now available to the US oncology community. Myriad Genetics is a reference lab of the highest quality and professionalism, with a broad reach in the US market,” said Salvatore J. Salamone, Ph.D., Chief Executive Officer of Saladax Biomedical, Inc. “This is a win-win situation for all involved - Myriad, Saladax, doctors, payers, and most importantly, cancer patients.”

About Saladax Biomedical, Inc.

Saladax Biomedical, Inc. is a personalized diagnostics company with its main R&D and manufacturing facilities based in Bethlehem, PA. Founded in 2004, Saladax is pioneering the development of an innovative line of proprietary Personalized Chemotherapy Management (PCM®) assays to test plasma levels of the most commonly used anti-cancer medicines. In the European Union, Saladax is marketing its 5-FU PCM Assay directly and has obtained a CE Mark for product distribution.

For more information about Saladax, visit http://www.saladax.com.

Source
Saladax Biomedical, Inc.

Researchers at the University of California, San Diego - led by 2008 Nobel-Prize winner Roger Tsien, PhD - have shown that bacterial proteins called phytochromes can be engineered into infrared-fluorescent proteins (IFPs). Because the wavelength of IFPs is able to penetrate tissue, these proteins are suitable for whole-body imaging in small animals. Their findings will be published in the May 8 edition of the journal Science.

“The development of IFPs may be important for future studies in animals - to find out how cancers develop, how infections grow or diminish in mice, or perhaps how neurons are firing in flies,” said Tsien, professor of pharmacology, chemistry and biochemistry at UC San Diego and a Howard Hughes Medical Institute investigator. Tsien was one of three scientists awarded the 2008 Nobel Prize in Chemistry for discovery of the Green Fluorescent Protein (GFP) and a series of important developments which have led to its use as a tagging tool in bioscience.

The limitation of using GFP in living mammals is that its wave lengths are not long enough to allow light to penetrate far enough to allow inner cells to glow with fluorescent light.

First author Xiaokun Shu, PhD, of the UC San Diego School of Medicine’s Department of Pharmacology and the Howard Hughes Medical Institute, coerced the phytochrome from the bacteria Deinococcus radiodurans to fluoresce - the first protein to glow in infrared and work in mouse models. A phytochrome is a photoreceptor - a pigment that plants and bacteria use to detect light - which is sensitive to light in the red and far-red region of the visible spectrum.

“IFPs express well in mammalian cells and spontaneously incorporate biliverdin, a green pigment that is present in humans and other mammals,” said Tsien. Biliverdin is the substance responsible for the yellowish-green color of a bruise as it fades, for example. Biliverdin normally has negligible fluorescence. However, Shu was able to coax the biliverdin-containing protein to fluoresce by cutting off the parts of the phytochrome that divert the energy of the light.

“We hoped that by doing so, the light’s energy wouldn’t go anywhere else but would instead go out and become fluorescent,” Shu said, adding that the protein is “moderately fluorescent, but we still have a long way to go.”

Tsien stated that, while this work is promising for future studies in animal models, he doesn’t think it will be applied directly to imaging in humans for several reasons.

“First, all fluorescent proteins derived from corals, jellyfish, and now bacteria are powerful in basic research because they are encoded by a gene,” said Tsien. “Introducing such genes into people would pose big scientific and ethical problems.”

He explained that, secondly, humans are still too thick and opaque for the infrared fluorescence to get deep inside our bodies, although scientists can now see faintly through a mouse with infrared, because mice are so much smaller.

The Tsien lab is working on a different project to develop a technique without these limitations, one that can be used for imaging in humans. His hope is that, one day, people will be able to go in for their annual check ups and know if they have cancer because tumors will light up by magnetic resonance imaging of diagnostic molecules.

But for now, Tsien, Shu and their colleagues at UC San Diego hope that the prototype they have developed can be used to make other, improved fluorescent bacterial proteins from among the huge numbers harnessed from other organisms - IFPs that can be used in important animal studies.

Source:
Debra Kain

University of California - San Diego

Agios Pharmaceuticals, the first biopharmaceutical company focused on discovering and developing novel cancer metabolism drugs, highlights the breadth and depth of research in the field of cancer metabolism presented at the 100th American Association for Cancer Research (AACR) annual meeting in Denver, Colorado last week.

Agios founders Tak Mak and Craig Thompson, as recognized leaders in the field, were featured in multiple cancer metabolism presentations and symposia at AACR in addition to the large volume of cancer metabolism scientific data presentations. Key highlights include:

– More than 50 abstracts/posters specifically in the field of Cancer Metabolism
– Symposium: “Cancer Metabolism: Back to the Future,” chaired By Tak Mak
– Symposium: “Targeting the Hypoxia Response in Tumors: Metabolic Implications”
– Mini-symposium: “Autophagy and Cancer”

Abstracts from the AACR Annual Meeting may be found at http://www.aacrmeetingabstracts.org.

“This year at AACR, even more than last year, the scientific engagement around cancer metabolism was truly extraordinary,” said Dr. Tak W. Mak, Ph.D., Agios Co-Founder and Director of The Campbell Family Institute for Cancer Research and Professor of The University of Toronto. “It is clear to me that the scientific advances within the field of cancer metabolism have captured a significant mindshare of the community and the time is now for aggressive translational science to help bring transformative drugs to patients.”

“As the first company founded to pursue cancer metabolism, we have a unique opportunity to lever and translate the scientific progress into meaningful advances in drug development,” said Kevin Starr, interim Chief Executive Officer, Agios Pharmaceuticals and Partner, Third Rock Ventures. “Since our founding only a year ago, the company has more than 40 scientists focused on advancing our pipeline programs towards the clinic and we have established a cell metabolism platform that is continuously informing our biological understanding of how to best select and target key metabolic enzymes in the cancer.”

Agios was founded by three of the foremost authorities and leaders within the field of cancer metabolism: Lewis C. Cantley, Ph.D., Director of the Cancer Center at Beth Israel Deaconess Medical Center and Professor of Systems Biology, Harvard Medical School; Tak W. Mak, Ph.D., Director of The Campbell Family Institute for Cancer Research and Professor of The University of Toronto; and Craig B. Thompson, M.D., Director, Abramson Cancer Center, University of Pennsylvania.

About Cancer Metabolism

Cancer metabolism is a new and exciting field of biology that provides a novel approach to treating cancer. Cancer cell metabolism is marked by profound changes in nutrient requirements and usage to ensure cell proliferation and survival. Research in the field has demonstrated that cancer cells become addicted to certain fuel sources and metabolic pathways. In cancer, this metabolic reprogramming is coordinated with proliferative signaling and regulated by the same oncogenes and tumor suppressor genes to ensure efficient proliferation. Glycolysis (sugar metabolism), fatty acid metabolism and autophagy (self metabolism) are three pathways shown to play a critical role in cancer metabolism. Identifying and disrupting certain enzymes in these, and perhaps other, metabolic pathways provides a powerful intervention point for discovery and development of cancer therapeutics.

Source
Agios Pharmaceuticals

Glivec® has been approved in the UK for the treatment of patients with the gastrointestinal cancer, KIT (CD117)-positive gastrointestinal stromal tumours (GIST), who have had surgery to remove their cancer and are at significant risk of the cancer returning.1 Data supporting this new use for Glivec demonstrates that 98% of patients receiving 400mg Glivec daily for a year after surgery to remove their GIST did not experience their tumours returning after 12 months compared to 83% of patients taking placebo.2

Approximately 900 people in the UK are diagnosed with GIST5 each year and approximately 86% of those diagnosed will undergo surgery to remove the tumour or tumours.6 However, if left untreated after surgery, almost 50% of all patients suffer a relapse within two years and recurrent tumours are often more aggressive and more difficult to treat than the initial tumours.3,4,7 The availability of Glivec for this patient population addresses a previously unmet need for GIST patients.

Roger Wilson, of patient group Sarcoma UK said: “After GIST surgery, patients have to live with the knowledge that there is around a 50 percent chance of their cancer returning. For those patients whose GIST does return, this can be devastating both physically and emotionally, even though Glivec can manage recurring GISTs. We hope that the future use of Glivec in the adjuvant setting will help to reduce the risk of GIST recurrence and provide reassurance to patients who live with the realities of GIST.”

Glivec is now licensed to be used to treat patients at significant risk of relapse following the removal of their tumour following approval from the European Medicines Agency (EMEA). The EMEA (the body responsible for the scientific evaluation of applications for European authorisation for medicinal products) says that patients who have a low or very low risk of recurrence should not receive adjuvant treatment.1

What is GIST?

GIST is a type of cancer called a soft tissue sarcoma i.e. a cancer of a supportive or connective tissue in the body such as fat, muscle, blood vessels, deep skin tissues, nerves, bones and cartilage.8 GISTs develop primarily along the gastrointestinal tract (digestive system) and often spread within the abdomen.9

Although the cause of GIST is unknown,10 75-80% of people with GIST carry KIT mutations.11 KIT is a protein in the body that plays an important role in the growth and survival of GIST.12 In patients with GIST, the KIT protein can mutate and become over active.5

The normal role of KIT is to provide the ’signal’ to cells in the body to grow and divide: this signal is not given continuously but can be turned ‘on’ and ‘off’ to limit cell division and growth. However, in people with GIST, a mutation in the DNA causes KIT to be continuously activated. Left ‘on’ all the time, KIT signals to cells to constantly grow and divide, driving the growth of GIST.5

Glivec in GIST

Glivec is a type of treatment called a tyrosine kinase inhibitor.13 It works in GIST by targeting the KIT protein, binding to it and preventing it from sending continuous signals to the cancer cells to grow and divide.14 Glivec has been available to treat people with unresectable GIST (GIST that cannot be removed through surgery) since 2002, but currently most people who have surgery to remove their cancer receive no further preventative treatment.

Glivec is now the only treatment approved to delay the return of this cancer, filling a previously unmet need for GIST patients.

References

1. EMEA opinion. Last accessed 7 May 2009

2. DeMatteo, R. et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. The Lancet. Online publication 19/03/09. DOI: 10:1016/S0140-6736(09)60500-6.. Last accessed 14.04.09

3. Van den Abbeele A., Benjamin R., Blanke C, et al. Clinical Management of GIST. Recurrence patterns and prognostic factors for survival. Highlights From the 2003 CTOS Annual Meeting and Helsinki GIST Symposium. http://www.ctos.org/newsletter/GIST_Newsletter0404.pdf, last accessed on 14.04.09

4. Demetri GD, Benjamin RS, Blanke CD, et al. NCCN task force report: management of patients with gastrointestinal stromal tumor (GIST)- update of NCCN clinical practice guidelines. J Natl Compr Cancer Network, 2007; 2(suppl 1):S1-S26.

5. NHS Cancer improvement. Guidelines for the management of gastrointestinal stromal tumours (GISTs)., last accessed 14.04.09

6. Novartis Data on File (GLI-001-01)

7. Life Raft Group. Managing Initial Recurrence., last accessed 14.04.09

8. Cancerbackup, Gastrointestinal stromal tumours(GIST); , last accessed 14.04.09

9. Choi et al, Response evaluation of Gastrointestinal Stromal Tumors. The Oncologist 2008;13(suppl 2):4-7

10. Cancer Research UK, Cancer help, What is the treatment for GIST - gastrointestinal stromal tumour? ; http://www.cancerhelp.org.uk/help/default.asp?page=6161, last accessed 14.04.09

11. Rubin BP, Heinrich MC, Corless CL; Gastrointestinal stromal tumour. Lancet. 2007 May 19;369(9574):1731-41

12. Corless, CL et al. Biology of Gastrointestinal Stromal Tumors. J Clin Oncol 22:3813-3825.

13. Summary of Product Characteristics. Glivec. Last updated 01/02/2008

14. Joensuu H, Fletcher C, Dimitrijevic S et al. Management of malignant gastrointestinal stromal tumours. Lancet Oncol 2002; 3: 655-64

About Glivec® (Glivec)

Glivec is approved in more than 90 countries including the US, EU and Japan for the treatment of all phases of Ph+ CML. Glivec is also approved in the EU, US and other countries for the treatment of patients with KIT (CD117)-positive gastrointestinal tumours (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (metastasised). In Japan, Glivec is approved for the treatment of patients with KIT (CD117)-positive GIST. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukaemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL. Glivec is also approved for the treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) who are not eligible for surgery. Glivec is also approved for the treatment of patients with myelodysplastic/myeloproliferative diseases (MDS/MPD). Glivec is also approved for hypereosinophilic syndrome and/or chronic eosinophilic leukaemia (HES/CEL).

Not all indications are available in every country.

For summary of product characteristics, please see here.

Source
Novartis