The GLG Pharma STAT Blog

STAT3, Cancer and Genetics - GLG Pharma

Posted by Richard Gabriel on Wed, Dec 26, 2018 @ 11:59 AM

STAT or Signal Transducer and Activator of Transcription is a biological process in our normal cells that is as biologists like to say 'highly conserved'. At the Moffitt Cancer Center, the work of researchers funded by the NIH has led to the important discovery that certain compounds inhibit STAT at the phosphorylation, dimerization and also at the DNA binding site. Unlike the trans-membrane activated receptors which are 'up-stream' from STAT, STAT is a biological function that works ultimately on the DNA.

This has led some researchers to worry about the toxic effects of STAT inhibiting compounds and frankly it is a justified concern. STAT is an important step in the reproduction of individual cells in our bodies and because it is highly conserved it is turned on very few times in a cell's life. Mostly during the cell division stage.

cancer stat 3, cancer and stat 3, stat 3 inhibitors

Cancer cells however, especially when they are metastatic or rapidly reproducing, have been shown to have STAT turned on all the time. So in cancer therapy, it is always a treatment that works specifically on cancer cells because they are rapidly reproducing or they are continually robbing nutrients from normal tissue. STAT inhibitors offer promise for treating metastatic cancers that are essentially run-away cancer cell reproduction in combination with standard chemotherapy treatment. Moffitt researchers have shown STAT to varing degrees of activation in over 23 different cancer types, including breast, pancreatic and neural cancers.

Cancer and stat 3, stat 3, stat 3 inhibitors, stat and cancer

The reason that the Moffitt is so interested in STAT3 inhibiting technologies is because we also have the ability to test for the activation of STAT3 in cancer cell types. Along with a person's cancer cell genetics as well as their personal ancestral genetics, tailoring a treatment regime for the patient with lower toxicities and higher efficacy is one of the major goals of our program. That is also why the Moffitt Cancer Center is also an investor in GLG Pharma. 

In these difficult economic times, GLG Pharma has found many new sources of funding to develop its STAT inhibiting technologies so that they may begin clinical trials as soon as possible. It is clear to all of us that work in biotech and pharmaceutical companies that there has to be a better way to fund the development of these important diagnostics and therapeutics. All of our current animal studies have shown that our STAT inhibitors have low toxicities but inhibitory effects on cancer growth and when combined with traditional chemotherapy could provide the knock out punch to the metastatic cancer cells. GLG has received support from local, State and Federal agencies to help develop its products and technologies. If you want to learn more about GLG, contact us at GLG Pharma.

Tags: GLG Pharma, STAT3, STAT3 inhibitors, STAT

GLG Pharma STAT 3 Blog

Posted by Richard Gabriel on Wed, Dec 26, 2018 @ 11:57 AM

Welcome the first blog of our new website, GLG Pharma, LLC. We will try to cover a variety of topics related to STAT 3 inhibitors, cancer in general as well as other informative articles that we find on health, nutrition, exercise and cancer prevention and treatment.

Cancer cells, STAT3 and cancer, STAT 3, cancer treatment and STATs

GLG Pharma, LLC is a Florida based company, located in Jupiter, Florida, near the Scripps Institute, Florida Atlantic University and the Max Planck Institute. It has affiliations with and has private equity partnerships with the Moffitt Cancer Center in Tampa, Florida, the Town of Jupiter and the Paragon Foundation of Palm Beach County.

If you want to learn more about our company, give us a call or send us an inquiry. We are happy to answer most questions. Our development plan for our four targeted products is emerging and we will from time to time report on our progress in pre-clinical and clinical development of these novel and exciting compounds for the inhibition of the STAT 3 mechanism in cancer cell metabolism. 

Tags: STAT3, STAT 3 inhibitors, STAT3 cancer, cancer diagnosis, STAT

Why Work on Treatment or Cures for Rare Diseases?

Posted by Richard Gabriel on Wed, Jan 28, 2015 @ 04:15 PM

“Highlighting Chronic Lymphocytic Leukemia (CLL)”

 

CLL, STAT3, GLG Pharma, STAT3 Inhibitors

 

The goal of every pharmaceutical and biotechnology scientist, physician and clinician is to save the patient’s life through an outright cure of the disease and if it can’t be saved then improve the quality of his/her life. Below are definitions of Rare Diseases, according to our friends at Evaluate Pharma[1]:

Evaluate Pharma Excerpt:

“The National Organization for Rare Disorders (NORD), which was instrumental in establishing the Act, currently estimates 30 million Americans suffer from 7,000 rare diseases. Prior to the 1983 Act, 38 orphan drugs were approved. To date, 468 indication designations covering 373 drugs have been approved. The success of the original Orphan Drug Act in the US led to it being adopted in other key markets, most notably in Japan in 1993 and in the European Union in 2000. Rare Disease Patient Populations are Defined in Law as:

  • USA: <200,000 patients (<6.37 in 10,000, based on US population of 314m)
  • EU: <5 in 10,000 (<250,000 patients, based on EU population of 506m)
  • Japan: <50,000 patients (<4 in 10,000 based on Japan population of 128m)

Financial Incentives by Law Include: Market Exclusivity

  • USA: 7 Years of marketing exclusivity from approval. Note: Majority of orphan drugs have a compound patent beyond 7 years. The market exclusivity blocks ‘same drug’ recombinant products, e.g. Fabrazyme (Genzyme, now Sanofi) vs. Replagal (Transkaryotic, now Shire). ‘Same drug’ exclusion can be overturned if clinically superior (mix of efficacy/ side effects), e.g. Rebif overturned Avonex’s orphan drug exclusivity (7 MAR 2002) 
  • EU: 10 Years of marketing exclusivity from approval.

Reduced R&D Costs:  

  • USA: 50% Tax Credit on R&D Cost
  • USA: R&D Grants for Phase I to Phase III Clinical Trials ($30m for each of fiscal years 2008-12)
  • USA: User fees waived (FFDCA Section 526: Company WW Revenues <$50m) 

Methodology on Classifying an Orphan Drug:  

"We, (Evaluate Pharma) have identified all products that have orphan drug designations filed in the US, EU or Japan. These are available as part of the core EvaluatePharma service. To further enhance analysis, we have defined a clean ‘Orphan’ sub-set of products following a number of criteria including:

  • First indication approved is for an orphan condition.
  • Products expected to generate more than 25% of sales from their orphan indications. 

This has led to the exclusion of drugs such as Avastin, Enbrel, Herceptin, Humira and Remicade, all of which have orphan designations for indications contributing less than 25% of sales.

  • Trial sizes, with smaller Phase III trials suggesting orphan status.
  • Drug pricing, higher prices were taken as an indicator of orphan status.
  • All sales analysis in the report is based on this clean ‘Orphan’ sub-set of products.” End of Evaluate Pharma excerpt. 

Chronic Lymphocytic Leukemia (CLL) is considered a ‘rare disease’. A great source of information on CLL[2] is the Leukemia & Lymphoma Society[3] which has over the years poured over $1 billion into research for Leukemia.  The information found in the PDF download (see reference) is excellent and is a foundation for understanding this disease and other leukemia’s as well.  

Some rare diseases have identified mechanisms of action that lay across the biological human horizon of diseases but aren’t as highly expressed or manifest themselves as a chronic lethal disease. One of the mechanisms sometimes associated with proliferative diseases that includes rare forms of cancer, is an abnormality in a major signaling pathway located downstream where many other pathways convey extracellular signals into the nucleus.  This is the case of the Signal Transduction and Activators of Transcription (STAT) and in particular, STAT3.  

At GLG Pharma we have focused on the STAT3 signaling pathway and its uncontrolled hyperactivity. Activation of STAT3 can be blocked at three different sites: 

  • Phosphorylation
  • Dimerization
  • DNA Binding

 STAT3 Inhibitor, STAT3, GLG Pharma, GLG-801, GLG-302

Three drugs are in the development pipeline. The first with the shortest path to the market is GLG-801. This is a repurposed drug and under US FDA rules for 505(b)(2) could be fast tracked for various indications and clinical trials might be initiated, as soon as funds become available, in patients with  rare diseases such as Chronic Lymphocytic Leukemia (CLL) and Gastro-intestinal Stromal Tumors (GIST). GLG-302, a new chemical entity (NCE) follows in the development cycle and is expected to be in the clinic in about 8 months from funding. GLG-202 is another NCE that will follow in the development cycle. GLG-801 inhibits DNA binding and both GLG-302 and GLG-202 inhibit dimerization of the STAT3 molecule, preventing its penetration of the nuclear membrane and the initiation of the transcription process and the continuation of the uncontrolled proliferation process.

Want to know more about GLG Pharma and Poliwogg? Raising awareness and helping us fight cancer! Then click on the Poliwogg picture and it will take you to the Poliwogg accredited investor site!

Poliwogg, GLG Pharma, STAT3 inhibitors, CLL, Chronic Lymphocytic Leukemia

Want to find out more about what compounds are in the clinic for CLL? Then click the button. Once you have signed up, we will email you the PDF document that provides you with compound structures and data on the activity of the compounds as well as their site of action on the leukemia cells!

 CLL in Clinic!

[1] Evaluate Pharma Report “Orphan Drugs 2014” http://www.evaluategroup.com/Default.aspx?goBack=true

[2] https://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/leukemia/pdf/cll.pdf

[3] https://www.lls.org

Tags: GLG Pharma, GLG, STAT3, STAT3 cancer, STAT3 inhibitors, Cancer, cancer diagnosis, STAT, cancer prevention, Alpha-1, Cancer Therapy, Rare Diseases

Why is GLG Pharma Different?

Posted by Richard Gabriel on Thu, Jan 02, 2014 @ 10:28 AM

Logo 5 24 13a resized 600

The most important difference is that GLG Pharma are not starting from scratch. We are veterans of many drug discovery, development, launch and successful drug treatment products. Many new companies that were launched and are being launched today in the Biotech and Pharma markets; were and are, started with such marketing and funding concepts as:

  • Transformational (new technology that changes an application within a defined market and industry)
  • Paradigm Shifting (new technology that changes an industry)
  • Innovative Transformations (new applications that open new markets of established market, technology and industry)
  • Ground Breaking Technologies (never before discovered technologies that opens completely new markets)
  • Lots of Investment Capital (Drugs, devices and diagnostics all require large amounts of capital)
  • Lots of equity dilution (founder’s equity is usually reduced to 1-5% of holdings after IPO’s, as a general rule)

GLG Pharma was started with a much simpler and understandable strategy for achieving drug and regulatory approval, a strategy that has two principles. Know your science and know your patient, coupled with shorter to market revenue generating products.

Many drug companies today have that strategy, but they are already funded. These companies are now selling products into a market and now they have become post-transactional savvy, compared to when they were first funded or seeking investment. So what has changed in the Biotech and Pharma world? In our opinion, a lot has changed.

Pharma and Biotech companies and startups have evolved as have the Pharma and Biotech markets in which we all operate. Today, investment for transformational, paradigm shifting and ground breaking technologies out of the high end institutions is still happening and will continue to do so; but the real question is; is this how a new Biotech and Pharmaceutical company should be launched? There is a reduced risk way to fund Pharma and Biotech. At GLG we have combined near term revenue opportunities in cancer with our pipeline development strategy. Our focus remains on the science and the patients, supported by investment and revenue from targeted approved products for prescription and over the counter products. These early stage revenue generators can help fuel and reduce the need for additional investment and subsequent dilution.

Each disease, whether it is AIDS, Influenza, Cancer, Schizophrenia, Alzheimer’s, Autosomal Dependent Polycystic Kidney Disease or any other terminal or chronic illness, have families and friends concerned for the patient. The patient is attended to by a cadre of physicians and clinicians who manage the disease and its treatment. It is a very complicated and sometimes a frustrating process, especially in the United States and also in Europe. It is frustrating not only for the patients and their families, but also for startup companies and entrepreneurs who want to launch new products and therapies for those patients. GLG’s focus on the science of disease and a patients therapy in treating proliferative diseases that have p-STAT3 as a mechanism, could help usher in new lower toxicity drugs that improve overall patient care. GLG can also monitor p-STAT3 levels in patients with a disease, alerting clinicians and patients as to the success or failure of a treatment regime.

Since the second great depression; starting in 2007 with the hedge fund collapse, life science technology companies; especially the Biotech and Pharma industries have been declining in value. However, the decline shortly after 9/11 in 2001; drug, biotech and diagnostic stocks and the startups have been on the proverbial slide down the slippery slope of little to no liquidity. Low liquidity for investors, low liquidity in equity markets, little to no availability of capital in bond markets. Adding to the downward spiral is the apparent unending series of regulatory disasters that have left the investment community shying away from anything remotely represented by or requiring an FDA filing and approval. Part of the regulatory perception problem was caused by large Pharma and large Biotech, by sometimes ignoring their responsibility to self-regulate their products, operations and clinical development in accordance with FDA and EMA regulations. A few very visible FDA actions against the industry can affect the entire investment and market landscape, Vioxx, Genzyme’s production failures and a whole host of other disasters, tangibly affected the investor psyche.

GLG’s management team have a performance history; out of the 16 drugs that have been developed and submitted to FDA review and approval by our collective team of professionals and the several FDA site audits of our former operations, 15 of those drugs were approved and none of us received or were cited in a FDA audit for any violations of 21CFR guidelines.

The same principle of respect for the regulatory process, applies to our respect for the patients; that our drugs will be treating. GLG are looking for a series of molecules that will be efficacious for the treatment of patients and have as little side effects as possible. All drugs have side effects that affect some or all patients, so having a chemotherapy agent that does not have side effects are rare. So why did we choose GLG-302, GLG-801, GLG-202, GLG-101 and 401 to advance into clinical development. GLG-302 is a compound that has proven itself in our pre-clinical evaluations as well as by a host of independent laboratories around the world. We have encouraged other laboratories to duplicate our findings and we have built up a successful and prominent following of researchers that now believe that inhibition of p-STAT3 is one of the keys to shutting down cancer cells that have become resistant or are proliferating at an exponential rate.

We are also looking at GLG-302 in combination with other standard chemotherapy agents as this compound has reversed chemotherapy resistant cells in vivo and in vitro, allowing a second course of treatment which eradicates the resistant tumors. This research has also led us to study cancer stem cells which survive standard chemotherapy treatments, these cancer progenitor cells go into a sort of remission and then spread throughout the body and start reproduction at a much higher rate. Cancer stem cells are resistant to chemotherapy treatments and are believed to be one of the major cause for cancer cell metastases. Cancer stem cells appear to be 100% up regulated with p-STAT3.

 GLG Pharma: Drugs, Diagnostics and Devices- delivering more than a drug ©

 

Tags: GLG Pharma, STAT3, STAT 3 inhibitors, STAT3 cancer, STAT3 inhibitors, Cancer, cancer diagnosis, STAT, cancer prevention, STAT3 mechanism

GLG-302 Selected by NCI for Funding in Cancer Prevent Program

Posted by Richard Gabriel on Wed, Jul 24, 2013 @ 12:45 PM

GLG Pharma’s STAT3 Signaling Inhibitor Selected for NCI’s PREVENT Cancer Preclinical Drug Development Program.


Jupiter, FL. July 16, 2013 – GLG Pharma, LLC announces scientific and financial resources of the PREVENT Cancer program of the National Cancer Institute of the NIH have been approved to study the effects of its STAT3 signaling inhibitor, GLG-302 as a breast cancer chemopreventive. The PREVENT Program is a National Cancer Institute-supported pipeline to bring new and novel cancer preventing interventions and biomarkers through preclinical development towards clinical trials.
The selected GLG Pharma study entitled “Evaluate GLG-302 in the Prevention of Mammary Cancers in the ER(+) Methylnitrosourea Rat Model and the ER(–) MMTV-NEU Mouse Model” using well established models of breast cancer will focus on the following areas:
1) Evaluate the MTD, effect on STAT3 in normal mammary tissue and oral efficacy of GLG-302 in mouse models of breast cancer.
2) Assess effects on tumor latency, incidence, multiplicity, and body weight.

This key study is an in-depth continuation of preliminary studies already conducted by GLG Pharma. In these studies GLG-302 was shown to suppress tumor growth in a number of animal models, to have a wide therapeutic index and was well tolerated.

In recommending approval of resources for the project, the PREVENT panel of external experts observed “This pathway is implicated in multiple cancer types. The value of the study goes beyond validating the pathway.”
According to the Centers for Disease Control and Prevention, aside from non-melanoma skin cancer, breast cancer is the most common cancer among women in the United States. It is also one of the leading causes of cancer death among women of all races. In the US in 2010, over 200,000 new cases and more than 40,000 deaths due to breast cancer occurred. The greatest achievement for this disease would be to treat high risk women who don’t have detectable breast cancer with an agent that is safe and well tolerated, and would prevent malignant conversion of normal breast cells to cancer.
Hector J. Gomez, MD, PhD, Chairman and CEO of GLG Pharma commented: “The NIH grant confirms the high level of scientific interest and the significant potential of our patented STAT3 signaling inhibitors in cancer prevention. This research program will provide important findings and form the basis for further evaluation and development of new therapeutic and chemopreventive agents in the prevention of breast and other cancers”. STAT3 inhibitors are important targets for cancer prevention and cancer treatment. Developed in collaboration with the Moffitt Cancer Center in Tampa, FL along with a companion diagnostic test, STAT3 targeting and monitoring is a program that the NCI has spent significant early research money to evaluate and advance. GLG is advancing these discoveries to the clinic and approval.

Landing GLG Pharma

About GLG Pharma
Founded in 2009 and located in Jupiter, Florida, GLG Pharma, LLC is a privately held, early stage, biotechnology company developing personalized therapies for patients with cancer and other proliferative diseases. GLG Pharma’s therapeutics are expected to aid in the treatment of a wide variety of cancers and address unmet needs in the multi-billion dollar anti-cancer market with potentially greater efficacy and fewer side effects than existing therapies. For more information on GLG Pharma visit: http://www.glgpharma.com

Tags: GLG Pharma, STAT3, STAT 3 inhibitors, STAT3 cancer, STAT3 inhibitors, Cancer, cancer diagnosis, STAT, cancer prevention

Startup Funds Still Available! Matching Grant for Investment in Cancer Drug Development.

Posted by Richard Gabriel on Thu, Jun 07, 2012 @ 11:02 AM

Institute for the Commercialization of Public Research Funds Jupiter Biotech Company

GLG Pharma Approved for Seed Capital Accelerator Program

Boca Raton and Gainesville, FL – June 1, 2012 - The Institute for the Commercialization of Public Research (the Institute) announced today that it has provided early-stage funding to GLG Pharma (GLG), a Jupiter-based company developing treatments based on technology licensed from the Moffitt Cancer Center in Tampa, for cancer and other proliferative diseases wherein cells grow or multiply rapidly. The Institute works with Florida’s research universities and institutions to support new company and job creation, and participants in the program must match Institute funding with private capital raised from angel investors and other sources. 

GLG Pharma is developing a series of patented inhibitors of activated Signal Transducer and Activators of Transcription 3 (p-STAT3).  The p-STAT3 protein is encoded by the STAT3 gene and is unique in the ability both to respond to extracellular signals and to regulate other genes directly.  In normal cells, the formation of the p-STAT3 protein is switched on and off in response to signals that control cellular function.  The presence of persistent levels of p-STAT3 is thought to play a key role in a number of diseases including cancer, psoriasis, polycystic kidney disease and Crohn’s disease.  GLG Pharma’s initial therapeutics are expected to aid in the  treatment of a wide variety of cancers with potentially greater efficacy and significantly fewer side effects than existing therapies in the $75-80 billion anti-cancer market.

GLG’s Executive VP Michael W, Lovell, Ph.D. stated that “this funding will enable us to advance the development of three product candidates and expand our collaborations with other research institutions in Florida. We appreciate Florida’s commitment to advancing the Life Sciences sector and these funds will enable us to raise additional capital to support our product commercialization efforts.”  

 “Companies like GLG Pharma demonstrate the promise of a diversified, knowledge-based economy in our state, and we are pleased to offer programs that help early-stage companies such as GLG Pharma achieve critical development milestones, said Jamie Grooms, Institute president and CEO.  “GLG Pharma also represents the statewide connectivity provided by the Institute, which facilitated bringing together technology from West  and Central Florida, management from Northeast Florida, and funding from Southeast Florida.”

About the Institute

Founded in 2007 as a non-profit organization, the Institute is Florida’s One-Stop-Shop for investors and entrepreneurs who seek to identify new opportunities based on technologies developed through publicly-funded research.  The Institute delivers programs that facilitate new venture and job creation through commercially-viable technologies in major industries that are driving the global economy.  The Institute also administers the Florida Research Commercialization Matching Grant Program launched in 2010, and the Seed Capital Accelerator Program launched in 2011.  For more information, visit .

About GLG Pharma

Located in Jupiter, Florida, GLG Pharma, LLC is a privately held, early stage, biotechnology company founded in 2009 to develop personalized therapies for patients with cancer and other proliferative diseases. GLG Pharma’s therapeutics are expected to aid in the treatment of a wide variety of cancers and address unmet needs in the multi-billion dollar anti-cancer market with potentially greater efficacy and fewer side effects than existing therapies. For more information on GLG Pharma visit: http://glgpharma.com

Tags: GLG Pharma, STAT3, STAT 3 inhibitors, STAT3 cancer, cancer diagnosis, STAT

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.