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, 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

The Entrepreneur's Real Valley of Death

Posted by Richard Gabriel on Thu, Apr 10, 2014 @ 02:00 PM

It’s always good to take a lesson from history but it is also good to keep in mind that arm-chair quarterbacking a play doesn’t address the real world problems of the next play. Since none of us can see into the future, our best analytical tools can only look at charts and graphs and project or predict that the chart will continue in the same direction or that the graph line doesn’t start plummeting downward. There are a number of technical and sophisticated mathematical algorithms that are used by stock trading firms that help investors of all sizes to maximize their returns. Up and down dramatic swings always tell us something about what could happen or what might happen next. The upward or downward motion of indicators also can tell something about a market such as valuation, either over or under. For example, right after 9/11 the internet bubble burst which was quickly followed up with the Biotech/Pharma/Lifesciences burst bubble. Valuations of public and private companies in both sectors plummeted.

I remember being at a Venture Fund conference in 2004 in New York City and the key note speaker said to the general audience that ‘… it didn’t matter the depth of investment, intellectual property or management team, the valuation of any startup is $5MM…’ peddle forward to the last Angel Investment conference I went to in Boston in 2013 and the key note speaker said ‘…it doesn’t matter what you think your company and technology is worth, we (Angels) take a minimum of 40% of your equity for $2 million’. I had the urge to punch the guy, just to teach him a lesson after he proudly followed it with ‘….one of our Angels came in to help add equity to the balance sheet and got a 9x return on $4 million in less than 6 weeks’. After I asked him what the founder’s got and how much they owned of the acquisition it turned out to be less than 11% split between two guys, which were fired after the acquisition and had to go out and get jobs! That scenario was last spring, nearly one year ago. While I don’t begrudge investors making money the argument of the rising waters floats all boats is quite frankly a pile of steaming manure. Valuations are still at the bottom and while they are rising, it’s not enough to offset the high failure rates of drug development in our industry.

So looking at the chart there was an uptick just prior to the crash in 2000 and there was also an uptick when the hedge funds crisis and the largest recession since the great depression (1929) in 2007 started. But starting in the first quarter of 2013 the zero line was crossed, meaning that VC’s were now going to make a lot of money. So now the upward climb of the tracking information looks like the North Slope of the last part of the climb at Mount Everest, so it is logical to assume that there is a top and that there will be a correction. How far, how deep and when it will occur? Who knows? I don’t.

What else does this dramatic step up in valuation increase tell us? The message to entrepreneurs might be to fight a little harder for your equity valuations but then again, most of the entrepreneurs that I know are still in the mind set of ‘give me money at any valuation’. So are the assets of a startup, which include people, are those assets undervalued and are the returns on investment over the top for the investors? Will valuations catch up with the market forces? The private capital market indexes seem to be doing so since 2013 and rather quickly. Will this translate to the Lifesciences industry? Slowly but deliberately. Eventually, the APP Bubble will deflate and all the shares that were priced into the stratosphere will find the other side of Mount Everest, the downside but then again, look at Google, look at Facebook. Looking at SharePost’s tracking of “after financed VC companies” that qualified investors can now invest in and do it through the recent announcement by the NASDAQ and the broker-dealer SharePost. One example is DropBox which now has a pre-IPO market capitalization of $9 billion. How many Lifescience companies that list on the US exchanges today have public market valuations over $9 billion? Not many. And that is the crux of the problem of our industry and the start-up’s that feed that industry and take ‘unnecessary risks’.

There are VC firms that have made a lot of money during the interim period, some of them went to China, India and Latin America, exporting US, UK and EU technologies, services, manufacturing and re-introducing those products and services back into their own economies and markets. Some of them were successful in selling their investments to pharma and biotech giants. And some of them and the companies that they funded, disappeared. Technology, jobs and opportunities lost. Neither Aspirin nor any approved antibiotics are made in the US any longer and haven’t been for quite some time. All of it outsourced.

The true picture of what happened during the ‘real valley of death’ in the life blood of the industry, capital can be seen below:

Link to glgpharma

 

The Valley of Death

Since January, 2014 there were 36 IPO’s from venture backed companies, 24 of them were biotech companies. The 36 companies raised $3.3 billion or about $83MM average with the highest being a medical software product company that will list on the NYSE Euronext with a high end raise of $200+MM. We have not seen this kind of IPO activity since the year 2000 in our industry and of course, everyone is now crying ‘Biotech Bubble’. Is it true? Is this another Biotech Bubble soon to burst? Only time will tell but if enough analysts and VC’s continue to vocalize the concept, a crash will surely happen. When, well that’s anyone’s guess. What will keep the crash from happening are the consistent and constant revenue increases and approvals of drugs for diseases.

So with all the improvements in drug development strategies have the odds yet improved? A recent study by Michael Hay et al stated:

“The study is the largest and most recent of its kind, examining success rates of 835 drug developers, including biotech companies as well as specialty and large pharmaceutical firms from 2003 to 2011. Success rates for over 7,300 independent drug development paths are analyzed by clinical phase, molecule type, disease area and lead versus non-lead indication status . . . Unlike many previous studies that reported clinical development success rates for large pharmaceutical companies, this study provides a benchmark for the broader drug development industry by including small public and private biotech companies and specialty pharmaceutical firms. The aim is to incorporate data from a wider range of clinical development organizations, as well as drug modalities and targets. . .

To illustrate the importance of using all indications to determine success rates, consider this scenario. An antibody is developed in four cancer indications, and all four indications transition successfully from phase 1 to phase 3, but three fail in phase 3 and only one succeeds in gaining FDA approval. Many prior studies reported this as 100% success, whereas our study differentiates the results as 25% success for all indications, and 100% success for the lead indication. Considering the cost and time spent on the three failed phase 3 indications, we believe including all 'development paths' more accurately reflects success and R&D productivity in drug development.” (Nature Biotechnology Hay, M. et al Nature Biotechnology 32, 40–51(2014) doi:10.1038/nbt.2786 Published online 09 January 2014)

Pictorially, our industry looks like this:

nbt.2786 F1 DrugSuccess resized 600

nbt.2786 F2 Drug Success resized 600

nbt.2786 F3 Drug Success resized 600

What does this say about the sudden boom in IPO’s? Since 2011, the improvement in drug approval success would not be great enough to justify the sudden resurgence of a market that has perhaps moved the approval pipeline stats up about 1-2% from the 1980-2000’s which was reported to hover at the 9-10% range (2011 we are in the 10-15% range the way I read the data). There is a danger though in over analyzing cumulative data across multiple diseases, it tends to blur the real progress that is often being made in a particular area of disease treatment. Blurring the disease categories with other areas that have always been notoriously difficult such as anything in the neural area, i.e. Parkinson’s, Alzheimer’s, Bipolar and Schizophrenia and let’s not forget Migraines, brings the overall industry down! Part of the higher failure rate is due to the lack of capital in the industry overall. VC’s abandoned the biotech/pharma/Lifescience space by the droves. So not only was it a death valley for return of investment capital after the last Biotech Bubble in 2000 burst, the rate of drug approval has gotten harder and the FDA and EMA are demanding more data, more information, more clinical trials and all this translates to higher risk, higher cost for any company when capital is short to non-existent.

Pharma companies and large Biotech’s that have lots of cash and the right talent and risk taking, reduce their risk by spreading across multiple drugs in development with multiple markers or targets that can be validated and might be unique. But the industry in the large Pharma and Biotech area has often proven itself to follow the Lemming mentality and our intrepid Authors state:

“Factors contributing to lower success rates found in this study include the large number of small biotech companies represented in the data, more recent time frame (2003–2011) and higher regulatory hurdles for new drugs. Small biotech companies tend to develop riskier, less validated drug classes and targets, and are more likely to have less experienced development teams and fewer resources than large pharmaceutical corporations. The past nine-year period has been a time of increased clinical trial cost and complexity for all drug development sponsors, and this likely contributes to the lower success rates than previous periods. In addition, an increasing number of diseases have higher scientific and regulatory hurdles as the standard of care has improved over the past decade.”

So in our industry we have heard much about the ‘Valley of Death’ coupled with living in the land of ‘Nosferatu’. It is so bad in our industry that the Government has recognized the problem and is attempting to provide funding and funding encouragement once a product or technology has a ‘proof of concept’. The Valley of Death is described as that space in between validation of a discovery (a pre-clinical state) where a compound is selected for advancement into clinical development and Phase 2 human clinical trials. The concept is that once a product reaches Phase 2 clinical trials, the investment community, the VC’s would then join in and fund the advancement of the products. The Valley of Death has always been there in drug development, large and small companies’ management must decide on which compound to advance into clinical development. A risky decision that can have dire consequences if the product fails in Phase 3 or the FDA and/or EMA agencies decide the drug is not efficacious or too toxic for the patient population.

At GLG we bring years of experience in selecting drugs and helping them get through the clinical development and approval process. We have over 15 approved drugs and nearly 30 diagnostics and several over the counter products that we all individually or as a team, have helped discover, develop and get approved. Sometimes the best drug is not always the one that has the lowest binding affinity, why? Well the drug might be great binding in vitro and in vivo models that are based around cell and animal model technology but have awful human clinical trial results. A good bio distribution, low toxicity, good efficacy is what everyone is searching for in our industry (along with a host of other very important characteristics etc.). So when you have a drug that has been tested across multiple animal models in different diseases and continues to knock out the disease target that is based on a biological marker, it probably will make it through clinical development and into the market. However, there are no guarantees and the risks are high but the sales often sky rocket like a new consumer device or product. Driving valuations of Biotech companies into the stratosphere, maybe even as high as Drop Box’s $9 Billion?

Also, want to learn more about new financing models? Contact Poliwogg by clicking the picture link below!

Poliwogg

Tags: GLG Pharma, STAT3

The New Way to Fund Biotech/Pharma/Lifescience Startups?

Posted by Richard Gabriel on Sat, Mar 01, 2014 @ 03:56 PM

Where is all the money?

If you are a company starting a 160 character limited social media communications product or an app to take money away from Verizon, AT&T and Sprint as well as all the piratical foreign phone services that cream you for many more dollars than the service are actually worth. For these social media and software app companies, investments is not a problem; or let’s say, that raising the money is less of a problem when compared to Lifescience startups current financial woes. If you’re a biotech/pharma/Lifesciences company startup, the odds of finding investment capital are better by playing the lottery in your home state. Steve Burrill a longtime supporter and follower of the Lifesciences industry commented at the Moffitt Cancer Center annual meeting for startups and technology, as the key note speaker that “…only 1 out of 150 startups receive funding from Venture Capital.” Another veteran of VC funding of sorts was involved with J&J’s Venture fund and commented that over 99.9% of the plans submitted to J&J venture funds were rejected out of hand. So far, the odds according to many observers; stack up against the formation and funding of a drug development company but there is hope and maybe a new route is here:

  • SBIR/STTR (this isn’t new) – While the NIH shows across different agencies an awarding of grants in the 15%+ average, it only reflects the number of applications that are reviewed versus awarded and not the number of applications submitted to the various agencies. Many applications aren’t even reviewed and rejected out of hand. No explanation for rejection is available, just rejection. Here’s a paper that reviews some of this for you. If you want to get an understanding of how the system works, Tony Fauci’s NIAID (National Institutes of Allergy and Infectious Diseases) gives a little tutorial. I’m still confused.
  • Government sponsored research on selected technologies and products. This is an up and coming area for the NIH and programs at various agencies select products across all diseases for funding. The catch is that none of the funding comes to the company directly but is rather paid out to third party providers to advance the technology or a product to the proof of concept stage or actual FDA application. Other resources may then become available such as matching grant funds and other incentives to get investors to the table. A good example is NCI’s Prevent Cancer Program. GLG’s product GLG-302 has been selected for this program. Check out your institution at the NIH where your technology can have a benefit to a patient population and see if they have such a program. If the NCI funds GLG-302 to its end point, which is an IND (Investigational New Drug Application) application to the FDA for long term cancer prevention therapy with our product, it’s worth $3.5-$4.5MM to the company, that the NCI will pay directly to 3rd party providers to accumulate the necessary data for the IND application. For GLG Pharma this is a miracle and we are so grateful to the NCI and the independent reviewer researchers that approved our submission. For women with breast cancer, this product could save their lives. The NCI wins, the taxpayer wins, the patient wins and we get a drug to market, so our investors will win.
  • Local, State and friends of the company money. This also includes your friends and family money. GLG has had lots of help here and personally, I will always be eternally grateful for all their support. So a quick overview and you can look for similar organizations in your area. We got support from the Town of Jupiter, FL for locating our business there and promising to stay there, which we intend to do!  FICR (Florida Institute Commercialization of Public Research) and organization committed to helping fledgling companies advance Florida created technology (our technology comes from the Moffitt Cancer Center in Tampa, FL) in the State of Florida. Along with Paragon Foundation actively supporting local Dade County businesses and we very much needed their help! Along with the local bank, Seacoast National Bank, that has stepped in to help support the Town of Jupiter and GLG. Our technology came from the Moffitt Cancer Center and University of Central Florida plus Yale University and the City of Hope Hospital, all working under an NCI Grant that funded the breakthrough technology of STAT3 inhibition diagnostic and drug treatment program. When our first drug begins to treat cancer or a proliferative disease, the patients will be the first to win and that couldn’t have happened if the NIH hadn’t supported the research at the Moffitt, Yale, City of Hope and UCF. These organizations will also be winners as well as collectively they own about 20% of equity and have royalties and milestone payments as the licensed technology advances. Bottom line, it takes many more people to make a drug company successful. Drug development is a team business and a company and its management as well as its investors, need to be determined and be willing to accept problems along the way and find ways to solve those problems. In that respect, drug development is no different than the teams that build the apps, Twitter, Facebook or Google. It just takes longer and it costs more. Lives are at stake in drug development and that’s the difference.
  • Crowd Funding. There are three aspects to Crowd Funding that can be used to change the face of funding for Biotech/Pharma/Lifescience companies. The first is the ‘not for profit’ (NFP) aspect of Crowd Funding, so how could this be used to benefit the development of new therapies? Groups of patients or patient interest groups could in effect under the not for profit moniker raise capital through donations to complete clinical trials or pre-clinical trials for targeted therapies and treatments. This vehicle could operate under the same principles as the NIH’s Prevent Cancer Program by first highlighting the goals and objectives of the funding and second by contracting the third parties to complete the work on behalf of the NFP with the information given to the chosen company or technology. Group associations such as the Polycystic Kidney Disease Foundation (PKD) can do this but on a very small scale. The National Breast Cancer Foundation does this but it’s mostly focused on providing funds to breakthrough research at Universities and Medical Centers and not the actual Development in ‘Research and Development’. If such a group were formed on Razoo or Charidy or Indiegogo or Rockethub or one of the other sites outlined by CrowdCrux. The company receiving these funds indirectly, could also agree to give back to the community by providing a portion of the profits to further fuel drug development or provide funds to foundations such as the PKD. The company could also have advocacy groups that are part of the annual review of technologies and accomplishments. For companies focused on cures and diagnostics for diseases, this shouldn’t be a problem. Razoo claims that over 90,000 charities have raised $200 million dollars using their site.
  • Crowd Funding for the public. The SEC for Crowd Funding has yet to complete the written guidelines for ordinary investors so that they can invest in startup companies or private offerings in private companies. The draft documents are available at the SEC site: Crowd Funding. “Under the proposed rules:
  1. A company would be able to raise a maximum aggregate amount of $1 million through crowdfunding offerings in a 12-month period.
  2. Investors, over the course of a 12-month period, would be permitted to invest up to:
  3. $2,000 or 5 percent of their annual income or net worth, whichever is greater, if both their annual income and net worth are less than $100,000.
  4. 10 percent of their annual income or net worth, whichever is greater, if either their annual income or net worth is equal to or more than $100,000.  During the 12-month period, these investors would not be able to purchase more than $100,000 of securities through crowdfunding.

Certain companies would not be eligible to use the crowdfunding exemption.  Ineligible companies include non-U.S. companies, companies that already are SEC reporting companies, certain investment companies, companies that are disqualified under the proposed disqualification rules, companies that have failed to comply with the annual reporting requirements in the proposed rules, and companies that have no specific business plan or have indicated their business plan is to engage in a merger or acquisition with an unidentified company or companies.

As mandated by Title III of the JOBS Act, securities purchased in a crowdfunding transaction could not be resold for a period of one year.  Holders of these securities would not count toward the threshold that requires a company to register with the SEC under Section 12(g) of the Exchange Act; (A quote from the SEC website). Each company would be limited to $1,000,000 per year funding via this vehicle. While not a panacea for drugs, it could get a company started, along with friends and family money as well as grants, a project could be advanced. The second new/old option:

  • Regulation D 506 (b) and 506 (c) regulation changes have been put in place and is a modification of Regulation D that has been in effect for some time. This is also known in money circles as the ‘Crowd Funding for the Rich’ as the requirements are investors must meet the criteria for investment. Again, direct messages from the SEC:

“Eliminating the Prohibition Against General Solicitation and General Advertising in Rule 506 and Rule 144A Offerings; A Small Entity Compliance Guide:

Introduction

Enacted in 2012, the Jumpstart Our Business Startups Act, or JOBS Act, is intended, among other things, to reduce barriers to capital formation, particularly for smaller companies.  The JOBS Act requires the SEC to adopt rules amending existing exemptions from registration under the Securities Act of 1933 and creating new exemptions that permit issuers of securities to raise capital without SEC registration.  On July 10, 2013, the SEC adopted amendments to Rule 506 of Regulation D and Rule 144A under the Securities Act to implement the requirements of Section 201(a) of the JOBS Act.  The amendments are effective on September 23, 2013.

Rule 506(b) of Regulation D

Section 4(a)(2) of the Securities Act exempts from registration “transactions by an issuer not involving any public offering.”  Rule 506(b) is a rule under Regulation D that provides conditions that an issuer may rely on to meet the requirements of the Section 4(a)(2) exemption.  One of these conditions is that an issuer must not use general solicitation to market the securities. 

“General solicitation” includes advertisements published in newspapers and magazines, public websites, communications broadcasted over television and radio, and seminars where attendees have been invited by general solicitation or general advertising.  In addition, the use of an unrestricted, and therefore publicly available, website constitutes general solicitation.  The solicitation must be an “offer” of securities, but solicitations that condition the market for an offering of securities may be considered to be offers.

Rule 506(c) of Regulation D

Section 201(a) of the JOBS Act requires the SEC to eliminate the prohibition on using general solicitation under Rule 506 where all purchasers of the securities are accredited investors and the issuer takes reasonable steps to verify that the purchasers are accredited investors.

To implement Section 201(a), the SEC adopted paragraph (c) of Rule 506.  Under Rule 506(c), issuers can offer securities through means of general solicitation, provided that:

  1. all purchasers in the offering are accredited investors,
  2. the issuer takes reasonable steps to verify their accredited investor status, and
  3. certain other conditions in Regulation D are satisfied.

An “accredited investor” includes a natural person who:

  1. earned income that exceeded $200,000 (or $300,000 together with a spouse) in each of the prior two years, and reasonably expects the same for the current year, or
  2. has a net worth over $1 million, either alone or together with a spouse (excluding the value of the person’s primary residence).
  3. An “accredited investor” may also be an entity such as a bank, partnership, corporation, nonprofit or trust, when the entity satisfies certain criteria.  The full definition of “accredited investor” is available here: Accredited Investor Definition SEC “. Finally the third option is to go public using the Regulation D capital raising vehicle (because most startups won’t get the necessary valuation or interest from merchant banks to warrant their trying to launch an IPO).

                                                     

  • A number of firms are playing in this space of Regulation D funding but Regulation D funding has also been used to launch public companies. While it is not the preferred route. Reg D initiated pre-IPO offerings are sometimes called a ‘Soft listings’ because the capital is raised privately and then the company files for a public listing on the NASDAQ (has to have a certain valuation, net equity and meet SEC requirements). This process is outside the normal ‘merchant banking’ where the banks float the offering and price the shares according to interest from their well-heeled clients which include individuals but also investment funds, hedge funds, pension funds and other sources of investment capital. Generally, ordinary folks are not eligible for standard IPO investments and usually none are eligible for the Reg D investment opportunities. A large amount of capital is raised using the Reg D filing and it is mostly done for hedge funds, VC funds and other investment type funds (SEC says about $1.5 TRILLION). It has been used some by startup companies, as was its intended design, but a vast majority of the capital that is raised is controlled by large, well-financed groups targeting the very companies (startups) that the regulation was first designed to help. Regulation D review article by the SEC can be found at: Reg D Review 2009-2012.
    • One of the companies in the Lifesciences area to promote ‘Crowd Funding’ for Lifesciences (Drugs, Devices and Diagnostics) was created by a broker dealer who had spent years on Wall Street, Jeff Feldman who well knows the ins and outs of raising capital. Mr. Feldman is the founder of Poliwogg an online ‘Crowdfunding’ site and he convinced Greg Simon to become its CEO and spokesperson and Sam Wertheimer, PhD to become Poliwogg’s Chief Investment Officer.
Poliwogg, GLG Pharma
    • Along with a dedicated staff of experts, Poliwogg will offer not only the Crowd Funding for the not so rich and famous but also offer Regulation D offerings to the Rich and Famous. Poliwogg is also in the process of setting up an investment groups where investors can place their capital for a broad based investment fund dedicated to the Lifesciences area and hopes to see the rate of funding through its portal to be over a billion dollars per year in funding. You can see GLG Pharma, LLC listed on their site.

So what does all this mean for startup companies like GLG Pharma that has a combination of revenue generating products already approved for the market (ready to license and launch), re-purposed drugs with new formulations for new indications (shorter time to approval and marketing), a selected developmental compound for the prevention of ADPKD, breast cancer and other proliferative disorders, a pipeline of rational designed molecules and a diagnostic to monitor the patients for disease and treatment? Come visit our website and find out about us at GLG Pharma or sign up with Poliwogg and learn more about GLG Pharma!

Tags: GLG Pharma, STAT3, STAT3 inhibitors, Alpha-1, Polycystic Kidney Disease, PKD

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.