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” 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, STAT3 inhibitors, Cancer, Cancer, cancer diagnosis, STAT, cancer prevention, Alpha-1, Cancer Therapy, Rare Diseases

Why Invest in Early Stage Drug Development for Rare Diseases?

Posted by Richard Gabriel on Mon, Dec 08, 2014 @ 02:54 PM

 

Ok, so in one of my past lives, as a member of our team at Pharm-eco Laboratories and with an excellent team at Vertex, together we worked on and helped advance Vertex’s Amprenavir (GSK’s Agenerase) which is now known as Phosamprenavir.   Amprenavir used to be known as VX-478 and we did scale up process development under cGMP and made a couple of tons of API. The discovery projects we worked on were mothballed or sent to someone else, who knows. 

Vertex bought Aurora in 2001 for an all-stock deal of $600MM and inherited the cystic fibrosis project in 2001. Aurora started in 2000 working on the project with the Cystic Fibrosis Foundation. The first capital investment by the CFF was $40MM to Vertex, the new landlord of a plethora of new screening technologies. 

The real point of this blog is this. $150MM invested in the Vertex technology over a nearly 13 year period, so about $11+ MM a year, average and the Cystic Fibrosis Foundation get back $3.3 Billion! 

So, we know the last two years sales for Vertex were $371MM and $470MM and assume that Vertex agreed to a 9% royalty (just a guess, it could be lower) to the Cystic Fibrosis foundation, then over a FIFTEEN YEAR (we added two years, one year on either end for negotiations etc.) period, giving the current payout, the Net Present Value of the $150MM investment; if you did the investment all at once with a discount of 8% over the period, is $915 million! Is that good enough for a VC firm? I don’t know but it sure is good enough for me! 

For more information on the deal, please go to an excellent article by Xconomy’s Deputy Biotech Editor Ben Fidler at http://www.xconomy.com/boston/2014/11/19/cf-foundation-cashes-out-on-kalydeco-in-3-3b-sale-to-royalty-pharma or just click on the picture below (also from the article by Ben Fidler, Thanks!).

STAT3, GLG Pharma, cystic fibrosis, STAT3 inhibitors

So why pay $3.3 billion for a drug that has a small market potential? Or a portfolio of drugs with a small market potential? Well, because it isn’t a small market potential! The disease target is also present in a variety of sub, less toxic and less lethal diseases and the mechanism is spread across much wider populations around the globe! Vertex was formed when Josh Boger came out of Merck and having worked for Merck back when Roy Vagelos ran the company, he had and still has a very impressive personal activity in promoting drug discovery and development in New England and around the world. I remember visiting Vertex for the first time when there were only 40 employees. Most of them were ex-Merck and ex-Biogen…great team! 

The drug targeting philosophy that Vertex probably does maintain to this day  is identify mechanisms of targeted therapy that could have broader applications in other diseases and focus on the rare diseases to get the FDA’s attention, fast track, cut time to market and then get the drug approved sooner rather than later. Well Cystic Fibrosis took a lot longer but the payoff was worth it for the foundation. Why is this model important? Because the foundation now has enough cash to really pour some capital into finding a cure, which has always, been their goal as it is for many other foundations. $3.3 billion sets up a heck of an annuity stream! 

Bottom line message is that this is a great case study and business model for a new way of funding biotech and pharma and that could revolutionize our industry! It’s not just a ‘buyout’ it is a reward to the committed not-for-profit groups that slog day after day against the insurmountable odds of the disease to raise capital for research and development for new therapies, against diseases that are unforgiving, ruthless and terminal. But this time, ~ thirteen years later, they are delivering on their commitment! Two new drugs for cystic fibrosis patients and the foundation now has a ton of capital to use for protecting its objective from the vagaries of the markets and funding drives for the next fifteen years or more! Congratulations CFF and congratulations to the team at Vertex, congratulations Josh Boger! 

If you want to find out more about funding development of new pharma and biotech, visit http://www.poliwogg.com and also go to Faster Cures at: http://www.fastercures.org 

GLG is developing a series of STAT3 inhibitors to treat orphan diseases particularly: Chronic Lymphocytic Leukemia (CLL), Polycystic Kidney Disease (ADPKD), A1- Antitrypsin deficiency and Gastrointestinal Stromal Tumors (GIST)! If you want to find out more about GLG Pharma and our pipeline of products, visit us at http://www.glgpharma.com or email me at rgabriel@glgpharma.com 

Cheers and as I have had the privilege to say to our soon to be former governor, Deval Patrick, ‘There is a better way to fund biotech’!

Poliwogg, STAT3, GLG Pharma, STAT3 Inhibitors

Tags: STAT3, STAT3 inhibitors, Cancer, Alpha-1, Rare Diseases, Alpha-1 Antitry, Rare Disease

GLG Pharma Attending Faster Cures Partnering Nov. 16-18 NYC

Posted by Richard Gabriel on Sat, Nov 15, 2014 @ 02:18 PM

GLG Pharma Attending Partnering For Faster Cure

GLG Pharma will be attending the Partnering for Faster Cures in New York City on November 16 through 18. The program is a matching of entrepreneurs looking for capital, investors and pharma companies looking for new ideas and technologies. The event is also peppered with researchers and patient advocacy groups as well as not-for-profits funding research organizations across a variety of diseases. Along with Richard Gabriel, COO of GLG Pharma, Greg Simon, CEO of Poliwogg will be attending.  In 2003, Mr. Simon along with Michael Milken founded Faster Cures  out the Milken Institute. 

Poliwogg, Greg Simon, GLG Pharma

Greg Simon, CEO; Poliwogg, Inc. 

Faster Cures’s goals are what the name implies, groups of patients, organizations, companies and entrepreneurs seeking a better way to fund Biotech and Pharma discovery programs so that they reach target patient populations sooner rather than later. 

GLG Pharma is raising funds using the new Poliwogg platform. Poliwogg offers private company investment on its site. This is an example of how accredited investors can now democratize their investments across a portfolio of new startup companies. 

“We are really excited about the Poliwogg platform as it offers investors direct access to startup companies such as ours” said Richard Gabriel; “Poliwogg’s platform uses standard SEC and FINRA rules and regulations for investment, it’s easy, secure and the valuations of the companies are in line with what previously only venture capital firms have had access to” Gabriel goes on to say. “For patient advocacy groups that want a direct opportunity to invest or for individuals that also want to invest directly in the development of a technology for a particular disease, Poliwogg offers an exciting and easy way to do it. Investors are able to spread their investments across multiple platforms and multiple technologies in multiple private companies.” 

Gabriel, GLG Pharma, STAT3 Inhibitors

Richard Gabriel, COO; GLG Pharma

Faster Cures features this event as a mean of accelerating drug discovery, development and funding. The new Poliwogg platform allows companies like GLG Pharma to raise capital and also provides a crucial first step to the potential public offerings. The valuation increases of a private company moving to a public offering will then go directly to the investors, employees and entrepreneurs participating in the private funding rounds.

 describe the image

 

 

Click on the Poliwogg!

Tags: GLG Pharma, STAT3, STAT 3 inhibitors, STAT3 cancer, STAT3 inhibitors, STAT3 inhibitors, Cancer, cancer diagnosis, Polycystic Kidney Disease, Cancer Stem Cells

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

Who is Your Patient Advocate?

Posted by Richard Gabriel on Tue, Jun 03, 2014 @ 01:54 PM

Where is Healthcare Today for Cancer Patients? Who is your advocate?

Patient advocacy is all about having a representative voice in clinical treatment. For Stage 4 cancer patients, the following excerpt is just one example of where clinical care is being directed by groups that are looking to minimize patient treatment opportunities. Bush, who is still a young man, might think differently if he is faced with a life threatening illness. Kierkegaard called it in existential religious terms; the ‘Leap to Faith’ that often occurs for an individual at the death of a parent, spouse, and/or a child or when an individual is faced with imminent death.  You can hear Bush's comments on: 

Jonathan bush of Athena Health. Dec 20, 2013 07:26AM on CNBC’s “Squawk Box” 

"If you cut out stage 4 cancer care, because most interventions shorten your life and makes you more miserable. Cut out all the chronic care [insurance coverage] and offer it [insurance] at $300 and then everything else is an add-on"..." [This quote is excerpted from Bush’s comments on the Affordable Health Care program and insurance and the state of health care in the United States; from his perspective.] 

Jonathan S. Bush (born March 10, 1969) is the co-founder, Chief Executive Officer, and President of Athena Health; a Watertown, Massachusetts based health care technology company founded in 1997.  In 2000, Bush raised more than $10M in venture capital funding to support Athena Health, which launched a successful IPO in 2007. Before founding Athena Health, Bush served as an associate of J. Bush & Company, Inc. and as a consultant at Booz Allen Hamilton, where he was a member of its Managed Care Strategy Group. Bush holds a Bachelor of Arts degree from Wesleyan University and a master’s degree in business administration from Harvard University.  In 1991, during "Operation Desert Storm", Bush served as a Combat Medic in the rank of Private First Class. He is the son of Jonathan Bush, cousin of former U.S. President George W. Bush, nephew of U.S. President George H. W. Bush, and brother of television presenter Billy Bush. Athena Healthcare highlights options for physicians on maximizing reduction in health care costs by recommending alternative treatment options. Today, Athena Health has a market cap of over $1.8 billion dollars. 

While Bush’s views on health care are not universal, the view does highlight what many healthcare pundits say is endemic with the industry, a parsimonious and conservative view of how patients should be treated and how much money should be allocated for their treatment. Groups like Kaiser Permanente offer My Doctor web site filled with information on cancer treatment options http://preview.tinyurl.com/kzcde8t as just one example of patient access to medical information. When a patient is fighting for their life; more information and top notch treatment or access to new therapies in clinical trials are sometimes what can make the difference. But someone needs to pay for that treatment and this is where the battle lines have been drawn. Cost versus treatment and access to treatment. Rich patient advocacy groups have been in existence for some time. A good example is ‘Best Doctors’; http://tinyurl.com/o38tj9m offers supreme ‘concierge’ services for a price. Clearly, “Best Doctors” carry premiums and services that are outside of the Affordable Care Act health care costs and the budgets of most families. Only 23% of their clientele are in the US, all the rest are outside of the US. They are a first rate organization and bring real value to the patients who can pay but that isn’t a model that is supported by the Affordable Care Act and is more in line with the rich will survive, the rest of us, well we have to make do with less. 

While cost savings are important to health care treatment, parsing out money for ‘approved’ and ‘unapproved’ conditions is tantamount to social and economic status engineering where only the wealthy can get the treatment they need and that treatment is only reserved for those patients that can afford it or have access to the networks of professional medical groups that can provide those services to the selected few. 

Also contributing to the lack of good and potentially new therapies for Stage IV cancer patients that could take a patient out of treatment and back into remission is the lack of funding for new therapies. The Affordable Care Act and the Jobs Act combined have created a potential new source of investment capital that is now available for startup companies. Patient advocacy groups can now raise capital using the Jobs Act Regulation D to raise sufficient amounts of capital to make FOR PROFIT investments in startup technologies. 

How Does the Jobs Act – Regulation D 506(c) Work? 

Regulation D 506(C) is an unlimited amount of capital with a limit of 2,500 shareholder/investors until reporting to the SEC regularly (quarterly and with annual audited financials) are required by law. The other restriction is that only persons or families (spouse) with combined incomes over a $300,000 or a net worth, excluding primary residence, of over $1.0MM, qualify as investors under Regulation D 506 (C). According to recent information there are about 8 million people in the US that qualify under SEC rules as “qualified investors” but a vast majority of them either don’t know that they qualify, aren’t interested in qualifying or have never invested in startup companies. It is estimated that less than 500,000 individuals or family units do this kind of private equity investing today. A part of this investing group is now known as ‘angel’ investors, gathering in groups of wealthy individuals and pooling their collective resources to raise initial capital for a startup. The problem with the angel groups today is that the capital initially invested in the drug area is a very small amount of the capital needed to advance a therapy or treatment to human clinical trials. Angel investments are typically in the $1-$3MM range and for that investment could consume up to 40% of the initial equity in a startup company. 

Patient advocacy groups can also organize under an investment moniker to raise capital as a “for profit” entity under the “not for profit” arm of their advocacy groups and begin investment in startup technologies and companies. Using Regulation 506, patient advocacy groups can behave the same way that some venture capital groups have operated for years, using Regulation D as the route of raising new capital for their funds (from qualified rich donors). Patient advocacy groups for example can use a part of their funds to support promising research at their favorite institutions (not for profit function), augmenting National Institutes of Health sponsoring of research. This one-two punch research support of NIH coupled with Not-for-profit grants provides the catalyst for new ideas, concepts and therapies through understanding of primary biological, chemical, structural and mathematical data and systems. In addition, a portion of their raised investment capital (the for profit advocacy group) can be used to invest in new therapies from discovery through New Drug Application approval by the US FDA or other similar regulatory body across the globe.

What Makes a Good Investment Target? 

The only investment target that we know something about is our own development pipeline and we will use this opportunity to provide an example of why a pipeline approach to drug development is a risk lowering strategy; as it is used by the well-financed and operating pharmaceutical and biotechnology companies and often ignored as a strategy for a startup by venture capital. It doesn’t have to be ignored by investors. The restriction of direct investment in startup companies and technologies if you qualify as an investment advocacy group or as a family or individual has been streamlined by the Jobs Act. The good news is that startup valuations in health care are still very low and have not hit the stratospheric pricing for pre-IPO stocks such as DropBox (valued at $10 billion prior to an IPO), a cloud based file sharing company. Most biotech startups are priced in the $10 to $20 million pre-money if they don’t have revenues, if they build revenues or close transactions; the valuation rises but not exponentially, rather more rationally. Usually when a startup gets acquired by a larger company, the valuations are often exponentially increased as pharma companies tend to price in future earnings of the acquired company in a buyout.

According to Life Science Nation (LSN) and its CEO and founder, Dennis Ford “it’s raining investors” in early stage clinical development projects (http://blog.lifesciencenation.com/) and here are two graphs extracted from his blog to highlight the interest expressed by investors who are signed up with LSN. 

Followed by a chart that is the result of one-on-one interviews by LSN staff with the investor group highlighted above:

Lifescience Blog

 

LifeScience 2

This can be good news for startup companies that have pipelines of development products and projects for at-risk patient populations. Reducing risk in early stage development projects in a startup company are crucial to moving a company forward, creating increase valuations for the early investors and completing strategic partnerships to help fill out the gaps in drug development, reducing risk and hopefully producing positive clinical product data. 

Diversity of Revenue Streams! 

When considering an investment in a biotech, early pharma or a lifescience startup; take a look at the product life cycles and depth of product line diversity within the company. In GLG Pharma’s case, we are already internationally diverse. We are negotiating a strategic partnership for drug development and approval of our lead product GLG-302, a p-STAT3 inhibitor that reverses Stage 4 chemotherapy resistant tumors and may allow for additional chemotherapy treatment. Market segmentation by regional partners is a good way to diversify risk and in our case, it provides us with a reliable partner in another part of the world that we would be unlikely to go to in the very near future. Providing your partners with access to your equity, product lines and development pipelines, creates meaningful incentives for shareholder risk reduction. 

An additional deal is underway in Europe, particularly in France where GLG Pharma, SAS is based. The SAS company will license an approved therapy treatment for actinic keratosis (precursor to skin cancer) and sell into France. Additionally, GLG-801, 302 and 202 are being formulated into patent protected formulations for dermatological applications. Our partner in the EU will formulate GMP material, check stability and provide samples to us for early proof of concept treatment under a physician’s Investigational New Drug program. Once proof of concept data confirms our scientific hypothesis, that the drug as a p-STAT3 inhibitor will work, then full clinical development will begin. First approval will be in Europe and the two companies will partner the drugs across the globe. GLG Pharma, SAS retains rights for France; our partner has rights for Germany, Austria, and Swiss speaking Switzerland, Japan and the UK. All other countries are partnered with a 50-50 split of profits. 

GLG-801 is a repurposed drug (already approved in another indication) that will have a faster time to market with the new skin formulation. The next product will be GLG-302, a New Chemical Entity. Following closely behind GLG-302 will be GLG-202 a rationally designed, composition of matter drug candidate. In addition, GLG Pharma has a diagnostic to monitor p-STAT3 during clinical and following drug approvals. Combining drug therapy and p-STAT3 diagnostic as well as other clinical marker monitoring, can perhaps reverse drug resistant tumor cells and make them more vulnerable to additional chemotherapy treatment! 

The GLG Pharma Pipeline 

Graphically we can represent the pipeline several ways:

STAT3 inhibitor pipeline

 

Diversifying a product pipeline across different diseases is also a way of reducing risk.

STAT3 Inhibitors

 

In addition, combining the strategy of ready to go to market products helps the company become an integrated company that has all the elements of a larger, fully funded pharmaceutical or biotech company with global initiatives and partners. Developing products within the treatment market for diseases is a global team effort, requiring a cross section of expertise usually not found in one single startup management team. While the GLG team has over 110 years of combined experience and has 15 approved drugs and 30+ diagnostics in the market, the core team still requires additional team members to advance its risk reduction strategy. Want to learn more about making a difference? Go to Poliwogg or visit our web site at GLG Pharma. We’ll also be at the International Bio Conference in San Diego partnering away!

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

Why is GLG Pharma Different?

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

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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

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.