The GLG Pharma STAT Blog

The Alpha-1 Antitrypsin Deficiency Walk!

Posted by Richard Gabriel on Mon, Nov 10, 2014 @ 11:36 AM

The Alpha-1 Question

Alpha-1 Antitrypsin Deficiency (Alpha-1) is an inherited genetic disorder and about 19 million people in the US are carriers of the gene. The problem is when genetic mixing creates the perfect Alpah-1 storm. Although there are many kinds of Alpha-1 Trypsin disease the most common amongst global populations is called the S and Z genes. 

For persons with both ZZ genes, which represent an estimated 100,000 persons in the USA and are likely to get liver and lung complications that will lead to transplant surgery. Persons with the SZ combination are not as likely but will be susceptible to chronic diseases such as emphysema, liver disorders and chronic pulmonary obstructive disease (COPD). About 3% of the COPD patient population test positive for the Alpha-1 disease according to the Alpha-1 Foundation. 

Why is GLG Pharma working and participating in raising money for Alpha-1 research? Simple, there is no cure for Alpha-1 and The Alpha-1 Foundation has invested more than $50 million to support research and programs to speed the commercialization of therapies for the elimination of Chronic Obstructive Pulmonary Disease (COPD) and liver disease caused by Alpha-1. Activated STAT3 mediates several diseases of the lung and liver and this may also be the case in Alpha-1 mediated liver and lung diseases. 

We want you to help the Alpha-1 Foundation by sponsoring Michael Lovell and Hector Gomez for a November 15th walk. This money will help the foundation continue its work in looking for cures as well as helping new products reach the market sooner rather than later. Michael Lovell our Executive Vice President and Hector Gomez our CEO are walking so please support the Alpha-1 foundation by donating through their link. Just click on the photo of your choice and donate to the Alpha-1!

                                           Support Hector Gomez:                                      Support Michael Lovell:

                                          HJGomez, MD, PhD                            IMG 7828 resized 600

Tags: GLG Pharma, STAT3, STAT3 inhibitors, STAT3 inhibitors, Cancer, Alpha-1, Cancer Therapy, Alpha-1 Antitry, Cancer Stem Cells, Chemotherapy, Alpha-1 Antitrypsin deficiency

Why are STAT3 Inhibitors Important in Cancer Therapy?

Posted by Richard Gabriel on Sat, Oct 11, 2014 @ 09:43 AM

STAT3 inhibitors are important agents for cancer therapy. STAT is an acronym for Signal Transducer and Activator of Transcription. STAT is a protein that is mostly found in the cell cytoplasm and is activated by upstream specific signals. It is first activated (phosphorylated by adding phosphorous to the protein to form p-STAT3), it then dimerizes (two p-STAT molecules bind together) and then it crosses the nuclear membrane, binds to the nuclear DNA and triggers a cascade of subsequent reactions that induces the cell to grow or die, a process called apoptosis. P-STAT3 is deactivated by the removal of phosphorous. In a normal cell this process turns on and off like a turn signal and lasts less than two hours. In cancer, the process remains on and cells don’t die, they continue to divide. 

There are seven STATs, each has a specific role in various cell functions. The one that interests GLG the most at this time is STAT3. As it turns out, measuring the p-STAT3 in a cancer cell tells the physician something really important, that this disease is in a run-away state of exponential growth rates. The molecule; p-STAT3, plays also a major role in acquired resistance to several anticancer therapies.   

In our normal tissues, STAT3 is what the scientists call a ‘highly conserved’ mechanism and is only produced and turned on when it is time for the cell to divide. In cancer, p-STAT3 is a non-stop mechanism. In diseases like esophageal cancer, multiple myeloma, pancreatic cancer, glioma blastoma, liver cancer, some lung cancers and triple negative breast cancer, p-STAT3 is present in approximately 65% of the tumors.

STAT3, Cancer Stem Cells, Cancer

Not a pleasant thought for someone possibly with breast cancer.  

The good news is that this abnormal process can be stopped and GLG is in a race against the clock. GLG’s compounds (STAT3 inhibitors), inhibit p-STAT3 and stop cancer cell proliferation. GLG’s inhibitors target the abnormal proliferation process at any of three different points of attack:

 1. Phosphorylation

 2. Dimerization

 3. DNA Binding

 Here is a cartoon we borrowed to help explain how our inhibitors of p-STAT3 work:

 

STAT3 

 

The arrows show where our molecules stop the abnormal proliferation.

  • Our phosphorylation (first two arrows) inhibitor is called GLG-101
  • We have 2 dimerization inhibitors (second arrow from the top) GLG-202 and GLG-302. GLG-302 is currently in the NCI’s Prevent Cancer program.
  • Our third inhibitor (third arrow from the top) is called GLG-801 and it is currently undergoing Phase 2 clinical trials in Chronic Lymphocytic Leukemia and has already demonstrated that in patients, it turns off p-STAT3. It is a repurposed drug, meaning that we can seek approval in cancer treatment under the FDA’s 505(b)(2) regulations (shorter and less costly to market approach sanctioned by the FDA). 

The 505(b)(2) application also means that the price of the new product, unless reformulated to deliver it to the patient in a more efficient delivery formulation, will have margins similar to the operating margins achieved by generic companies.  

What’s even more startling is that in the laboratory GLG-302 has been shown to reverse chemotherapy resistance in over 9 commercial anti-cancer drugs and across 10 different types of cancer!

9 Commercial Anti-Cancer Drugs Developing Resistance in Patients 

 
 
  • Bortezomib                                $2.8 billion
  • Cetuximab                                 $703 million
  • Cisplatin                                    $2.0 billion
  • Doxorubicin                               $450 million
  • Docetaxel                                  $1.5 billion
  • Paclitaxel                                   $1.0 billion
  • Tamoxifen                                  $140 million
  • Vemurafenib                               $675 million
  • Vorinostat                                   $150 million

Total Sales of Drugs whose  Resistance can be Reversed by GLG-302: ~$8.4 billion

 

 

 

 

 

 

 

 

 

 

                                                                   Cancer types that have been found to develop acquired resistance to chemotherapy are:

  1. Breast (Triple Negative)
  2. Liver
  3. Head & Neck
  4. Melanoma
  5. Multiple Myeloma
  6. Ovary
  7. Urinary Bladder
  8. CTCL (cutaneous T cell lymphoma)
  9. GIST (gastrointestinal stromal tumor)
  10. Esophageal

By reversing the acquired resistance to chemotherapy, with our GLG-302 p-STAT3 inhibitor, the cancer cells once again become susceptible to chemotherapy treatment and are killed. We have seen this work reported in multiple independent laboratories across the world and across the listed cancers. If a cancer cell does not show p-STAT3 upregulation, then our compounds will not benefit the patient. If however the p-STAT3 is elevated, we could improve patient outcomes!

Want to find out more about our Company? Are you a qualified investor? Sign up at Poliwogg. Follow us as we will post more information on our website. Thank you for your time and consideration!

Poliwogg, GLG Pharma

 

Richard Gabriel, BS, MBA

COO

GLG Pharma, LLC

President

GLG Pharma, SAS

Tags: GLG Pharma, STAT3, STAT3 inhibitors, STAT3 inhibitors, Cancer, Cancer Therapy, Cancer Stem Cells, Chemotherapy

STAT 3 publications are numerous and we hope that the following links will help you better understand it's importance in cancer cell metabolism and cancer cell death. Inhibiting STAT 3 is an important mechanism for encouraging cancer cell death. Using STAT 3 inhibitors with other traditional cancer chemotherapy should help improve patient outcomes. Linking a diagnostic with a STAT 3 inhibitor will also help reduce patient side effects as well as potentially improve patient outcomes.