Dallas, TX based AveXis has announced that company co-founder John Carbona has resigned from his position as CEO. Mr. Carbona will remain a Director of AveXis. This announcement stems from a succession plan, the development of which has been in process as AveXis advances clinical development of its lead program for the treatment of Spinal Muscular Atrophy (SMA).
AveXis got its start in Dallas through BioLife Cell Bank and is being financed by White Rock Capital Texas, Inc. and others. In this way, executive members of BioLife Cell Bank are involved in AveXis as well. Appointed as BioLife’s Chief Executive Officer in April 2012, Mr. Carbona played an integral role in creating and developing the company’s strategic move from a cryogenic stem cell laboratory to a clinical-stage biotech. This was accomplished by negotiating early-stage strategic alliances that uniquely paired the Dallas start-up with established corporate entities, academic researchers, and their respective universities.
The company’s name, AveXis, which has both scientific and mythological meaning, is derived from scientific terms involved in the company’s work plus the name of a mythological figure. Hence, Av = adeno-associated virus (AAV) serotype 9; ve = vector; X = DNA helix; is = Isis, the goddess of children, nature and magic, who is particularly symbolic since the company’s initial focus, SMA, affects children, and because they hope to rework nature with a little magic (in the form of brilliant scientific discovery) to treat it.
“We are fortunate to have had John lead our firm through a very dynamic growth period,” comments John D. Harkey, Jr. , AveXis Chairman of the Board. “John has provided tremendous efforts in establishing AveXis as a premier gene therapy company both in the US and abroad. We would like to thank John for his tireless commitment to AveXis which has advanced the goal of helping families with children with SMA.”
The AveXis Board of Directors has implemented a plan to build the company’s management team to support growth and advancement of its lead development program for treatment of SMA. The company has engaged a leading executive recruiting firm and initiated a search for a new Chief Executive Officer. In the interim, Mr. Harkey will serve as AveXis Executive Chairman.
“We are pleased to be in a position to recruit a world-class leadership team to build the company to the next level,” says Mr. Harkey. “We are very encouraged by the progress to date in developing our ChariSMA gene therapy program for SMA in collaboration with Nationwide Childrens Hospital and Ohio State University, and remain completely dedicated to advancing this new treatment as rapidly as possible.”
“I am proud of the team we built here in Dallas and the accomplishments to date at AveXis. I will forever be indebted to the SMA researchers around the world who helped AveXis and most importantly the families and children with SMA who supported AveXis and me in our infancy. I look forward to the continued growth and success of the company as I watch from a new vantage point,” says Mr. Carbona.
After graduating university with a pre-medical science degree and forgoing his desire to become a dentist, Mr. Carbona taught high school biology before beginning his business career as a sales executive with Mead Johnson, a division of Bristol Myers, and worked with Yale New Haven Hospital in developing new infant formulas and later at Stryker Corporation under the legendary John W. Brown. Relocating from the Northeast to Texas, Mr. Carbona’s interest, aptitude and merit in the manufacturing industry propelled him from a sales representative of a struggling one-product company to President and CEO of an international medical company.
Mr. Carbona held or co-held six patents and 30 trademarks in his name, which were sold in a $500M industry roll-up sponsored by Bruckmann, Rosser, Sherrill & Co. in 1998. As a board member of Pontio Communications, a facilities-based wholesale supplier of high-speed transport, Digital Subscriber Line (DSL), and broadband network services, Mr. Carbona was part of the team that pioneered privatization of public utilities in Texas. In 1999, he aided in the sale of Pontio to El Paso Gas, a Fortune 100 company, for almost $200 million.
Known for his innovative marketing and sales approaches, Mr. Carbona originated the use of cross-marketing alliances, shared revenue agreements, and direct advertising within the health care industry, which are all now common practices. He earned a Bachelor of Science in biology from the University of South Florida.
A native of Long Beach, NY, Mr. Carbona was a competitive swimmer and ocean lifeguard growing up. He was also inducted into the American Powerboat Association Hall of Fame in 1991 for winning the United States title in ocean racing. Among all of his awards and accomplishments, Mr. Carbona — the son and grandson of New York policemen — is proudest of his two civilian accommodations given to him for citizens arrests. Mr. Carbona is unmarried, and splits his time between Dallas, Texas and Ft. Myers, Florida.
Avexis Central Focus: Spinal Muscular Atrophy
Incorporated in July, 2013, AveXis was conceived and established by Mssrs. Carbona and Harkey to create complimentary industry alliances for collaboration on development of treatments for unmet medical needs, with Spinal Muscular Atrophy — a genetic disorder that causes progressive muscle wasting and robs the afflicted of physical strength and leads to mobility impairment due to its effect on motor nerve cells in the spinal cord — the company’s first choice of focus.
SMA eventually results in loss of the ability to walk, eat, or breathe, and is the number one genetic cause of infant death worldwide, and the second most common inherited autosomal recessive disorder.
The disease is caused by a mutated or malfunctioning survival motor neuron gene 1 (SMN1) on the 5th chromosome. In healthy people, SMN1 produces a protein that encodes SMN, which is widely expressed in the eukaryotic cells critical to nerve function and muscle control. In SMN’s absence, motor nerve cells lose their capacity to function properly, and eventually they die, resulting in progressive and often fatal debilitation, muscle weakness, and difficulty performing basic life functions such as breathing and swallowing, although intellectual and cognitive abilities remain unaffected. Symptoms often manifest as weakness in controlling head and neck movements, with muscular control of limb movement also affected.
In SMN1 gene mutancy, the severity of SMA is modified by the copy number of the SMN2 gene. A mutated SMN1 gene and no copy of the SMN2 gene will result in embryonic lethality.
AveXis and other biotech companies are pursuing research and development of SMA treatments including gene therapy, stem cell therapy, SMN2 upregulation, SMN2 splicing and SMN stabilization. Several clinical trials of therapies designed to affect SMA progression of are also in progress, mainly for Type 1 and Types 2/3 of the disease.
A rare/orphan disease affecting approximately 1 in every 6,000 -10,000 children born. The SMN gene is carried on chromosome 5, and in order to be inherited, both parents must carry it. If both parents carry the gene, there is a 25 percent chance that any of their children will manifest SMA. Roughly one-in-40 to one-in-80 normal men and women will be a genetic carrier, across all races and ethnicities.
The four main types of SMA — designated I, II, III, and IV — are distinguished by age of onset and peak physical milestone achieved. Typically, proximal muscles and muscles of the lung are first affected, and eventually other body systems as well, especially in early-onset types.
Type I, also known as Werdnig-Hoffman disease, is the early-onset form, in which symptoms occur prior to 6 months of age. The most severe form of SMA, Type I accounts for 58 percent of SMA incidence at birth, and results in inability to sit without support, difficulty with breathing and swallowing, and is lethal for 90 percent of victims by two years of age.
Type II SMA, alternately known as Dubowitz disease, is characterized by onset at between six and 18 months of age, and is the second most prevalent form, accounting for 29 percent of SMA incidence at birth. Type II patients frequently have three copies of the SMN2 gene, and will vary in rapidity of disease progression. Typically, Type II patients will be able to sit but not to stand upright. Body muscles weaken, with respiratory system dysfunction a major concern. Life expectancy of Type II patients is somewhat reduced, but many survive into adulthood with careful medical attention.
Type III SMA, AKA Kugelberg-Welander disease or juvenile SMA, is juvenile onset, with symptoms first manifesting when the patient is older than 18 months. Life expectancy with Type III is near normal, but persons affected may lose their ability to walk unassisted and have increased risk of developing scoliosis.
Type IV, adult onset SMA, is extremely rare, and begins to affect patients’ abilities at between 30 and 40 years of age. Life expectancy with Type IV SMA is normal, but patients may eventually need a wheelchair for mobility.
Currently there are no approved therapies for SMA, and current drug therapy has proved unsuccessful in stabilizing or reversing the disease. Consequently, treatment for SMA patients is supportive and palliative. Respiratory care is critical for Type 1 and Type 2 SMA patients, and assistive technologies for mobility and scoliosis are available.
However, AveXis and other biotech companies are pursuing research and development of SMA treatments including gene therapy, stem cell therapy, SMN2 upregulation, SMN2 splicing and SMN stabilization. Several clinical trials of therapies designed to affect SMA progression of are also in progress, mainly for Type 1 and Types 2/3 of the disease.
AveXis recently launched a new website specifically focused on SMA: http://www.smastudy.org — an integral element to AveXis’s multi-pronged effort to increase awareness of ongoing and upcoming SMA treatment clinical trials. While the company’s corporate website is centered on AveXis, the new SMA-focused website’s role will be to communicate directly with parents of children with SMA who are looking for information and treatment options.
The new website presents information about ongoing open enrollment in the Gene Transfer Clinical Trial for SMA Type 1 (NCT02122952), and about a gene therapy product developed by Dr. Brian Kaspar, of Nationwide Children’s Hospital and ReGenX Biosciences, which has been licensed to AveXis for development and commercialization. The AveXis gene therapy biologic is currently referred to by its development code name “chariSMATM.” There are also links to connect patients, parents, and families with resources like the several SMA focused organizations, foundations, and support and advocacy groups worldwide, as well as links to other clinical trials available for patients with all SMA types.
“It is very important for AveXis to remain rooted and communicate effectively to the community which is so supportive of our work in gene therapy. The intention of this new website is to empower people around the world to learn about SMA, to inform them of their clinical trial options, and to provide links to educational support organizations, which are always useful when looking for answers,” commented Mr. Carbona on the Website launch.
A Phase 1 gene transfer clinical trial of AveXis’s chariSMATM in SMA Type 1 infants is underway at Nationwide Children’s Hospital in Columbus, Ohio, which received IND approval and Fast Track designation from the FDA in September 2013. “Fast track,” refers to a hastened phase in the drug review and approval process, and signifies that the FDA can expedite the review and development of the scAAV9.CB.SMN gene therapy product which, in preclinical work, has been shown to slow the progression of SMA symptoms. The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of self-complementary scAAV9.CB.SMN as a treatment of Spinal Muscular Atrophy type 1 (SMN1).
The Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1, a Phase 1, single-site, dose-escalation study, will evaluate the safety and efficacy of gene transfer in SMA Type 1, delivering the SMN gene intravenously using the adeno-associated virus serotype 9 (AAV9). Principal Investigator is Jerry R Mendell, MD, of the Research Institute at Nationwide Children’s Hospital Center For Gene Therapy.
chariSMATM utilizes AAV9 to deliver the functional SMN gene to patients. In preclinical studies, AAV9 has been shown to cross the blood-brain-barrier, delivering SMN to motor neurons and significantly improve survival and motor function in an animal model of SMA.
A particularly fascinating aspect of AveXis’s chariSMATM gene transfer therapy is that it hitches a ride, so to speak, on the tiny virus which can cross the blood-brain-barrier — essentially harnessing a virus to deliver medicine. In preclinical studies, AAV9 has been shown to be effective in delivering SMN to motor neurons and thereby significantly improve survival and motor function in an animal model of SMA.
The chariSMATM (scAAV9.CB.SMN) approach is to introduce fully functioning copies of a SMN gene, intended to supplement the body’s SMN protein production. According to AveXis, the newly introduced SMN gene exists in an episomal or extrachromosomal form, meaning that it will not integrate into the cell’s genome of the. The cell will begin continuous production of the SMN protein from new copies of the SMN gene. In October, 2014, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to AveXis’a scAAV9.CB.SMN product chariSMATM, to treat Spinal Muscular Atrophy patients. Orphan Drug Designation is granted by the FDA Office of Orphan Drug Products to drugs intended to treat rare diseases or conditions affecting fewer than 200,000 people in the U.S. There are estimated to be between 25,000 and 50,000 SMA patients in the U.S., Europe and Japan.
AveXis is working with leading European medical research centers on figuring out the financial and regulatory hurdles that need scaling in order to initiate a mirror image chariSMATM trial in Europe in 2015. The company is also reaching out to domestic and international foundations and patient advocacy groups to increase overall awareness of their clinical trials.
AveXis also recently launched its C.A.N. Program — a new initiative designed to “Contact All Neurologists” in order to increase awareness of ongoing and upcoming SMA clinical trials, and to inform neurologists as to how they can help shape future patient recruitment in SMA trials.
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Nationwide Children’s Hospital