Spotlight on Bio Advances
Dr. Ginette Serrero, founder and CEO of A&G Pharmaceutical.
Maryland Company: 
Risk taking 101

A&G Pharmaceutical signs agreement with Mayo Medical Laboratories, its most recent collaborator
“Forging strong partnerships is essential”, says Dr. Ginette Serrero, founder and CEO of A&G Pharmaceutical. Partnering with oncologists at the University of Maryland at Baltimore County, allow her direct access to cancer patients. “These visits always give me perspective about the challenges which these patients are facing in comparison to my challenges of translating my research on breast cancer to the drug and diagnostics market. It grounds me and reminds me of my original goal: to make a product that would help cancer patients”.

The most recent collaboration in 2012 shows broad implications of her company’s work. “Mayo Clinic will receive a non-exclusive license to certain patent rights and proprietary antibody reagents for the detection and measurement of progranulin in blood which will enable the first commercial blood test to predict progranulin mutation status in patients suspected of frontotemporal dementia (FTD). FTD accounts for 5- to 10-percent of all cases of dementia, and even more by some estimates”. The blood test will be available late 2012 at the worldwide locations of Mayo Medical Laboratories.

Dr Serrero states, “A&G has pioneered and patented research investigating expression of progranulin in breast cancer and lung cancer. Research has shown that breast cancer patients have an elevated level of progranulin when compared to healthy individuals. We are delighted that our clinical studies with breast cancer patients and development of progranulin antibodies and assays will also help FTD patients.”

Dr. Serrero established A&G Pharmaceutical determined to develop an antibody therapy that targets the GP88 biomarker. At present, its three products include one therapy and two diagnostics. Dr. Serrero pioneered the science of the GP88 glycoprotein biomarker at the University of Maryland at Baltimore County while a full professor. Her dedication and commitment to this fight are apparent. She resigned a full professorship to work full time at A&G Pharmaceutical.

How do you develop the risk taking ability to leave a lifetime in the making full professorship in the sciences to build a business? She credits her personality as a determined fighter combined with the ability to balance many factors at once in problem solving. An early influence, her father was an ear, nose and throat doctor in her childhood home of Niece, France where she was exposed to his dedication and perseverance towards the healing of his patients. Also, the loss of a personal and courageous fight against cancer came to a very close aunt who believed in her and her research even before the pathbreaking discoveries arrived.

Dr. Serrero has enjoyed mastering the skills of business development for which most scientists are not formally trained. Raising capital for the company has come in diverse forms. Initially, the research begun in labs at the University of Maryland at Baltimore County was supported by funding from the Department of Defense and the National Cancer Institute – National Institutes of Health which allowed employment of her graduate students at the company. Attracting significant partners came next. The state of Maryland awarded the company with a challenge fund and then an enterprise fund receiving the “Best Graduate Company” Award at the 2009 Maryland Incubator of the Year Awards.

There have been other key alliances. Dr. Serrero explains in 2011 Issue 12 of International Innovation, “With our partner (Celltrion, a leading publicly traded biopharmaceutical company in South Korea),

We developed GMP – Good Manufacturing Practice – Master and Working cell banks and the antibody from these cell banks has been used to design a formulation suitable for intravenous use in human studies. We have developed a scaled GMP manufacturing process including downstream purification; and we have produced a pilot batch of antibody for long-term stability studies and investigational New Drug-enabling toxicology studies. Once we have data from those studies , we can approach the US Food and Drug Administration”.

Other strategic partners arose. In 2007, The Avon Foundation Breast Cancer Prevention Research Initiative awarded A&G an $870,000 grant which is the first ever awarded by the foundation to a private company. The funds allowed the company “to conduct multicenter clinical studies focused on measuring levels of A&G’s proprietary breast cancer biomarker, GP88, in blood and tissue samples from breast cancer patients. Results of the studies could provide the basis for developing a blood test that would enable early detection of breast cancer. Also A&G is developing a tissue biopsy test that would help pathologists and oncologists predict risk of recurrence in breast cancer patients”. A day may come when we might be able to say au revoir to the famous pink ribbon.
Success Stories
“A&G has pioneered and patented research investigating expression of progranulin in breast cancer and lung cancer. Research has shown that breast cancer patients have an elevated level of progranulin when compared to healthy individuals. We are delighted that our clinical studies with breast cancer patients and development of progranulin antibodies and assays will also help FTD patients.”
Trending toward multiple pathways
 By E. Teresa Touey, Editor and Publisher, Spotlight on BIO Advances
Larger, longer clinical trials describe the historical trend of drug development of Alzheimer’s, a brain disease developing in someone in the United States every sixty-seven seconds.* Presently, the investment of resources in targets have produced mixed results for patients afflicted by the disease and their families, usually the primary caretakers. Over the short-term, there is some relief. Four U.S. FDA approved drugs temporarily slow worsening of the symptoms of Alzheimer’s disease for about 6 to 12 months for about half of the patients afflicted. However, no real long-term answers to solving the devastating brain function decline has been discovered.

Strategy questions arise: Q: Where should investors risk funds? Q: What approach should researchers and drug developers use for targets? Q: How will patients and their families be supported in the rising numbers of diagnoses with an ageing baby boomer generation with rising caretaker costs? One clinical stage biopharmaceutical company, Anavex Life Sciences Corp., is attempting to give its own answers. With its array of assets and management team headed by President and CEO Christopher U. Missling, PhD, MBA, Anavex is developing novel drug candidates to treat Alzheimer’s disease, diseases of the Central Nervous System, and various types of cancer.  

Anavex announced on March 13, 2014, the private placement of $10 million in principal amount of convertible debentures with several institutional and accredited investors, including U.S. and international healthcare funds.

The funds will be used to initiate a Phase 1b/2a clinical trial of ANAVEX PLUS and advance its product portfolio. ANAVEX PLUS is a promising, potentially novel combination drug for Alzheimer’s disease that combines ANAVEX 2-73 with donepezil (Aricept®), the world’s best-selling Alzheimer’s drug with $4 billion in annual sales.

“This financing significantly enhances our financial strength and is a critical step to advancing our clinical trials in Alzheimer’s disease,” said Dr. Missling. “With funding now in place, we are scheduling to initiate a Phase 1b/2a trial of ANAVEX PLUS in Alzheimer’s patients as soon as possible. We will also look at opportunities to strengthen our product pipeline.”
In context of some recent failures in the Alzheimer’s drug development landscape around “bapi” and “sola” as well as other research insights, Anavex’s management team has concluded from its pre-clinical data that targeting multiple AD pathways simultaneously at different levels of the disease stage might be needed. This conclusion has been facilitated by the clear synergistic memory effect (up to 80%) in combination of ANAVEX 2-73 with donepezil (Aricept®) and up to 7 points cognition improvement in ADAS-Cog at 12 weeks and 5.5 points at 26 weeks in humanized calibrated realistic critical network computer model.**(See UPenn connection below)
Thus, Anavex’s team has reduced clinical trial risk allowing for shorter trial length and a smaller patient test population. For those patients afflicted with a range of symptoms over time from noticeable cognitive decline of forgetfulness to an inability to manage personal affairs to a loss of speech and locomotion thus needing full-time care, a move in this direction may lead to a new trend in Alzheimer’s drug development. It could provide some ingredients needed to discover more effective treatments to create not only a new market opportunity with multibillion dollar projections but to bring some peace to the families facing these realities.  

Innovation is needed on the policy front in healthcare systems and governments which will be facing an expected growth in the dollars spent on caring for Alzheimer’s patients . The current $203 billion in costs is expected to rise to $1.2 trillion by 2050 as well as growth from the current more than 5 million Americans living with Alzheimer's disease to as many as 16 million by 2050. In addition, for every $27,000 Medicare and Medicaid spent on caring for individuals with Alzheimer's, the National Institutes of Health (NIH) spends only $100 on Alzheimer's research. As the Association points out, “providing funding to enable the continued, effective implementation of the National Plan to Address Alzheimer's Disease to meet the goal of preventing and effectively treating Alzheimer’s by 2025 (will require) bipartisan collaboration and resource commitments to strengthen Alzheimer's care and support while accelerating research toward therapies that can slow, stop and ultimately prevent this disease.”***

*Source: Alzheimer’s Association 2014 Alzheimer’s Disease Facts and Figures Report 
  Page 19
**Source: A current issue of peer-reviewed International Pharmaceutical Industry Journal, IPI, published “The Anticipated Clinical Effect of the new Alzheimer Drug ANAVEX PLUS in a Predictive Humanized Cortical Cognitive Model for Alzheimer’s Disease,” by Drs. Missling, Maurice and Geerts, Chief Scientific Officer of In Silico BioSciences (ISB), Lexington, MA and Adjunct Professor at the School of Medicine at the University of Pennsylvania, and, Athan Spiros and Patrick Roberts of ISB)
***Source: Alzheimer's Association 2013 Alzheimer's Disease Facts and Figures report

Christopher U. Missling, PhD, MBA
President and CEO, Anavex Life Sciences Corp.