The GLG Pharma STAT Blog

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”



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


Posted by Richard Gabriel on Tue, Jan 06, 2015 @ 02:54 PM

(What's In It For Me?)

Many years ago Maureen Doerr at Doerr Associates[1], (pronounced Door) explained to me how to sell an idea to an unknown prospect. Notice that I said prospect and not customer because Maureen reasoned, rightly so, that a prospect becomes a customer when they buy something from your company. A prospect sometimes doesn’t know they want to buy something from you until you Advertise or Promote the ‘something’. Stick with me on this.  WIIFM is simply “What’s in it for me”? It has stuck with me ever since.


Maureen Doerr, WIIFM, Doerr Associates, Advertising, Marketing 

Maureen Doerr, President Doerr Associates 

This is a simple concept that should, theoretically, drive just about everything your organization does to make your products and services and your company a success, including research!  All facets of the business you are planning to build should be geared to answering the WIIFM of your prospects and also your continuing customers. And making sure that what is driving your research and development and ultimately your manufacturing, marketing and selling engine, is focused on answering the WIIFM for new prospects, new customers and loyal customers. The answers to each group may not necessarily be the same. Sometimes the products aren’t the same either, think Sonites and Vodites[2], for those of you that know what those two products are, you know what I’m talking about…for the rest of you, try googling the terms, its fascinating stuff! 

In health care, especially in disease oriented healthcare, our prospects are the patients, advocacy groups, healthcare insurers, government agencies, physicians, clinicians, families, institutions and the research and development community at large. Add to that the investment community which includes venture capital, angel capital, friends and family, private equity, institutional capital, research funds and grants, government funds plus the stock market; it’s a pretty complex scenario. It is so complex, that everyone tries to simplify it just in order to try and understand or attempt to understand just what the heck is going on in the market. I know I have that problem; this is way too complex for my puny brain.  

Oversimplification can at times add to the confusion and miss the WIIFM of our target prospect audience, new customers and existing customers. Sometimes these groups don’t want the same thing. Take me for instance, I love my Blackberry (still do) and everyone laughs at me. But I grew up with a Blackberry when it would only do email and within a company network, you could do something that today is called ‘texting’ from one person to the next, securely

If Blackberry had been paying attention to Apple, Microsoft, Google and others including Samsung, and the younger generation, they might still have the lion’s share of the market or at least a cougar’s share. But they didn’t pay attention to WIIFM's. So how did that happen? I don’t know and I’m not smart enough to guess. Only the ex-management team and employees of Blackberry (RIM) could tell us. Same thing happened to Xerox, IBM, Bell and Howell, Polaroid, Atari and countless others. The same process will happen to the many now ‘darlings’ in healthcare. It seems impossible for any of us to see past the ends’ of our noses and it seems almost impossible for any of us to predict what the next new technology breakthrough will be or where it will occur across the globe. Blackberry always satisfied my WIIFM’s because I am a loyal customer, stupid, stubborn but loyal. 

I’ve always tried to put myself in the shoes of the prospect that I want to talk to. Sometimes this works, but not always. The prospects I want to talk to are the 8.5 million qualified accredited investors[3] in the United States BEFORE the Securities and Exchange Commission shrinks that number down to about 2-3 million through added restrictions. Everyone wants to talk to them and so far, as a group, they are pretty clammed up. I don’t think we yet understand their WIIFM’s. Or at least I don’t. 

A really good summary of the Accredited Investor market was put out by the Angel Capital Association and addressed to the Honorable Mary Jo White Chairperson of the Securities and Exchange Commission[4] calling for White to NOT restrict Accredited Investor Requirements further as only about 200,000 of the 8.5 million Accredited Investors actually participate in Regulation D investments. Just to provide some perspectives, according to the article, there were 31,000 Reg D offerings issued in 2013 compared to 954 public offerings. In that same year, $980 billion was invested under Reg D (granted they were not all accredited investors because it includes businesses and institutional investors etc.) compared to $250 billion in the IPO market raised during the same time period.


SEC, Mary Jo White, Chairperson, Regulation D, Reg D 

The Honorable Mary Jo White, Chairperson of the SEC 

So let’s do some elementary simple math of averages:


Reg D, SEC, Regulation D 

Only 2.3% of the total Reg D market is composed of Accredited Angel Investors capital ($23billion) and they on average risk $115K of their average $2.5MM net worth or less than 4.6% of this AVAILABLE resource for investment! Looking at this issue from the far-out and somewhat unreliable perspective of averages, the total 8.5 million accredited investors who have an average net worth of, wait for it, at a Net Worth of $1.0mm represent about $8.5 trillion or some percentage of that number, to possibly invest or put at risk. And of that 8.5 million Accredited investors, the the current $23billion represents 0.27% of their average net worth! In other words, what makes the SEC think that suddenly 99.7% of the NON PARTICIPATING accredited investors are suddenly going to throw all of their assets to the wind and invest in Regulation D companies? 

So why is the SEC so focused on Restricting Accredited Investors? They hardly made a dent in the Regulation D market! Don’t get me wrong, if you or me as an entrepreneur, got funding from one of the 200,000 investors in 2013 we would be delighted! 

Reality is that nearly all of the Regulation D market is composed of SOPHISTICATED Institutional investors who are by the way, capturing all the upside of new companies that are now listing on the exchanges! 

Obviously, we as an investment seeking community of struggling lifescience entrepreneurs are seeking investments for our research and development endeavors to cure, treat or eradicate disease, don’t know the WIIFM of the other 8.3 million Accredited Investors, many of whom remain silent, unapproachable and generally disinterested in healthcare, until it’s too late, either for them as individuals or for a family or friend suffering from the sudden onset of a disease or chronic ailment. Then, sometimes, they may become motivated. 

So do the math. For 31,000 offerings that are on the Reg D filing there are probably another 10x that never make it to that stage, 300,000 plus good ideas that go virtually nowhere or flounder: in regione vivorum mortuis[5]. The Secretary of Energy, Steven Chu supposedly coined this term, ‘the valley of death’, apparently in 2009; but I swear I have heard it before[6]. This Valley of Death is the no-finance-available zone between idea and application and the finding of customers that are willing to pay for the discovery, whether it’s a product or a service. 

First and foremost, Reg D filings are NOT CROWD FUNDING investment opportunities. REGULATION D is presently reserved for the very rich as well as institutions, funds and capitalists who have gathered the wherewithal to fund new startups or advance a startup from a slow startup growth to accelerated high growth by providing capital for expanding manufacturing, marketing and sales to meet the new demand. So far, 8.3 million rich, accredited investors are not interested in participating in one of the largest investment opportunities in the history of the United States. Why is that? Well we haven’t figured out their WIIFM’s, now have we?

Interesed in GLG Pharma and our fight against cancer and proliferative diseases? Visit us: GLG Pharma
Want to find out more about Accredited Investor Funding to fight cancer? Visit: Polliwogg
poliwogg,, accredited investor, glg pharma, glg, cancer





[5] in regione vivorum mortuis: “In the Land of the Living Dead”


Tags: GLG Pharma, accredited investor, angel investor, angel investors, accredited investors, WIIFM, GLG

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.