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Blazing the trail
September 2011
by Amy Swinderman  |  Email the author


A number of biotechnology firms dedicated to stem cells have been launched in the past few years, thanks to strong venture capital funding in geographic areas where government and science have favored stem cell research, according to Frost & Sullivan.
Notably, California ranks highest, with a total of 10 firms dedicated to all kinds of stem cell research receiving either venture or IPO-backed funding. It's interesting to note that Geron Corp., which works with hESCs, has the maximum market capital value at $605 million, despite the fact that adult stem cell research receives more funding.
Geron, located in Menlo Park, Calif., is considered by many to be the top biotechnology company in the field of stem cell research. Since its founding in 1990, Geron has been granted more than 260 patents. The company has two anti-cancer products in human clinical trials. In 2009, Geron received FDA approval to begin Phase I testing in humans of GRNOPC1, an eSC-based drug designed to treat specific forms of spinal cord injury through remyelination of damaged axons. Geron also has several other embryonic stem cell treatments that are still in the preclinical phase, including GRNCM1, a treatment for heart disease, and GRNIC1, a treatment for diabetes.
Here, we feature a handful of other companies that stand out as leaders in this market, according to Frost & Sullivan.

Company: Aastrom Biosciences Inc.
Ann Arbor, Mich.

Developing enhanced autologous cellular therapies for the treatment of severe, chronic cardiovascular diseases
Borrowing its name from its location—"Ann Arbor Stromal" was its first moniker—Aastrom Biosciences Inc. began as a device company but is now known as a developer of process technologies and devices for cell therapy applications, including stem cell therapies and gene therapy.
Unlike some of the other companies operating in the same space, Aastrom manufacturers the autologous cells it uses in-house. A small quantity of bone marrow is taken from a patient's hip, and in a 12- day process, Aastrom expands the cell populations found in the extracted marrow. Then, in a single inpatient procedure, the expanded mixed-cell therapy produced from this process—called ixmyelocel-T—is administered to the same patient to promote healing of the affected tissues.
"We have designed our own highly automated, fully closed cell processing system," explains Tim Mayleben, Aastrom's CEO, president and director. "It is the best device in the world for processing autologous cells. And our success has been to think both strategically and medically about the kinds of diseases our particular technology is well-suited for."
Specifically, those are critical limb ischemia and dilated cardiomyopathy—critical cardiovascular diseases that currently have limited or no treatment options. The company is in a Phase III clinical trial to study ixmyelocel-T patients with critical limb ischemia and two Phase II clinical trials to study the therapy in patients with dilated cardiomyopathy.
"These chronic, long-term, progressive diseases are well-suited to our technology," says Mayleben. "There are literally no treatment options for these patients, and of the options that are available— amputation, heart transplant, etc.—these are limited in availability and expensive. Our vision at Aastrom is to get the first autologous cell therapy product in physicians' hands and used by patients, so we can change the way that medicine is practiced. Our technology also has applications in other disease areas that we are just now starting to explore."

Company: Advanced Cell Technology (ACT)

Santa Monica, Calif., and Marlborough, Mass.

Retinal degeneration; blood and cardiovascular diseases
Although ACT was principally focused on hESCs, the company now also has some interesting work involving induced pluripotent stem (iPS) cells. ACT has three cellular product platforms based on its stem cell technology—the first-ever proven alternative method for successful hESC generation without harm to the embryo, called the "single-cell blastomere" technique.
First, the company is focused on commercializing its hESC-based Retinal Pigment Epithelial (RPE) therapy for degenerative retinal disease, for which it recently initiated two Phase I/II clinical trials. Retinal degeneration can cause a variety of blinding diseases, including retinitis pigmentosa, Stargardt's disease (juvenile macular degeneration), age-related macular degeneration (AMD) and other degenerative diseases of the retina.
"One of the great things about working with the eye is that you don't have the immune rejection issues you would find in other parts of the body," says Gary Rabin, chairman and CEO of ACT.
ACT is particularly focused on AMD, which afflicts more than 30 million people worldwide and is the leading cause of blindness in people aged 60 and older in the United States. And as average life expectancy continues to rise, it is predicted that the incidence of AMD will only continue to rise in tandem. Dry AMD, the most prevalent form of the disease, represents a $25 billion to $30 billion market in the United States and Europe alone, and there are currently no approved therapies available for this condition.
On July 14, ACT announced the dosing of the first patients in each of its two Phase I/II clinical trials for Stargardt's macular dystrophy and dry AMD using RPE cells derived from hESCs. The patients were treated by Dr. Steven Schwartz, retina division chief at UCLA's Jules Stein Eye Institute. Both patients successfully underwent the outpatient transplantation surgeries and are recovering uneventfully.
"It would be great if the end result of these clinical trials is if we arrest the decline of age-related macular degeneration," says Rabin. "The math works out readily to see how this could be the largest drug therapy of all time— this could be bigger than Lipitor."
ACT is also developing its hESC-based Hemangioblast (HG) platform for the treatment of blood and cardiovascular diseases in a partnership with CHA Biotech of Korea.
Finally, the company is focused on advancing its Phase II- approved Myoblast autologous adult stem cell therapy for the treatment of chronic heart failure, advanced cardiac disease, myocardial infarction and ischemia.
ACT owns or licenses more than 150 patents and patent applications related to stem
cell therapy and regenerative medicine. The company also recently announced a collaboration with Roslin Cells for the storage and distribution of eSCs using ACT's Blastomere technology.

Company: Aldagen
Location: Research Triangle Park in Durham, N.C.
Employees: 16
Focus: Developing proprietary adult stem cell products for tissue repair and regeneration, particularly in the cardiovascular market

When a company decides to enter the stem cell research arena, it must make a very important decision: how and from where to derive the cells they will use. For Aldagen, a clinical-stage biopharmaceutical company developing proprietary regenerative cell therapies, that question served as the foundation for the formation of the company.
In 2002, Aldagen's founders took technology developed at Johns Hopkins University and Duke University and started a commercial enterprise. The technology identifies, selects and isolates specific adult stem cells that express high levels of the enzyme ALDH, which plays an important role in controlling the developmental state of stem and progenitor cells. It converts vitamin A into retinoic acids, which regulate genes and influence the differentiation of blood, neural, endothelial and other types of stem and progenitor cells.
Because Aldagen uses this technology to collect autologous cells from a patient's own bone marrow, the risk of potential rejection of the injected cells in a patient is minimalized, says Edward L. Field, the company's chief operating officer.
"When you compare us to other companies, we have a unique cell population that no one else has," Field says. "What we do is very different, but also very simple. We don't manipulate, culture or expand cells, so we are able to fairly rapidly produce and deliver them to the patient."
Compared to some of the other companies we are featuring here, Aldagen is fairly young, having operated for less than 10 years. Field attributes the company's youth to "the fact that a lot of us are trying to do what has never been done before."
"If you think about commercializing new technology in our industry, it usually takes 20 to 25 years from the seminal event to get commercial products to market, and stem cells are no different," he says.
Companies like Aldagen will be able to realize the promise of this groundbreaking research "if we can achieve the next milestone in stem cell research, which is putting Phase III studies and data sets on the table," says Field.
Aldagen is headed in that direction, as it is beginning Phase II studies involving therapeutic candidates for critical limb ischemia and ischemic heart failure. Also, in May, the company—along with its collaborator, the Los Angeles Brain and Spine Institute (LABSI)— announced the enrollment of the first subject in a clinical trial that studies ALD-401, a unique stem cell population derived from a patient's own bone marrow, for the treatment of ischemic stroke.
"The stroke market alone presents billion-dollar market opportunities," says Field, "because there are no therapeutic options or small-molecule drugs to treat it. In addition, our therapy is a regenerative, restorative kind of therapy that has the potential to take costs out of the healthcare system by keeping patients ambulatory. We have talked to payors, and they are very encouraging as we move this program forward."

Company: Neuralstem Inc. 
Founded: 1996
Location: Rockville, Md., and San Diego; plans to open subsidiary in China soon
Employees: 16
Focus: Using its patented neural stem cell technology to treat central nervous system diseases

In January 1992, attorney Richard Garr sat at the bedside of his four-year-old son Matt at Children's Hospital in Washington, D.C., helplessly watching his difficult recovery after an 18-hour procedure to remove a brain tumor.

Nearly 20 years later, Garr is the president and CEO of Neuralstem Inc., a publicly traded biotherapeutics company that is making headlines for its stem cell clinical trials to treat amyotrophic lateral sclerosis, (ALS, commonly known as Lou Gehrig's disease) and depression—and eventually, other diseases of the central nervous system (CNS).

Bonded to the father of one of his son's classmates, Dr. Karl Johe—a staff scientist at the Laboratory of Molecular Biology of the National Institute of Neurological Disease and Stroke— Garr saw an opportunity to alleviate Matt's suffering. In 1996, he and Johe joined forces to commercialize Johe's Human Neural Stem Cell technology.

The technology allows for the isolation of CNS stem cells from tissue; the expansion, in vitro, of each cell up to a billion-billion times, or 60 doublings; and the controlled differentiation of the cells into mature, physiologically relevant human neurons and glia that can be used to treat CNS diseases and conditions. This provides a unique window for traditional drug discovery and genomic applications, Garr says.

"We screen against ourselves, and we screen against physiologically relevant human cells, so we can really see what's actually happening, which is predictive of what will happen in humans," he explains.

Neuralstem has 14 patents to its name—issued all over the world—with more than 20 others pending. The company's work with stem cells is evenly divided between using them to develop actual therapeutics and to screen against for drugs. The company currently has two Phase I clinical trials underway.

The first is evaluating the safety of Neuralstem's spinal cord stem cells in the treatment of ALS, and notably, is the first ALS stem cell trial to be approved by the FDA. In June, Neuralstem announced that 12 patients being treated at Emory University in Atlanta safely received injections in the lumbar region of the spine, prompting the trial's Safety Monitoring Board (SMB) to unanimously approve advancing the trial to transplantations in the cervical region. Neuralstem hopes these injections can help alleviate the breathing and swallowing difficulties that often lead to death in ALS patients.

Neuralstem's second Phase I trial is testing NSI-189, the lead compound in the company's neuroregenerative small-molecule drug platform, for the treatment of major depression. Phase Ia is testing the drug in healthy volunteers for safety and tolerability.

Neuralstem hopes to conclude both trials within the next five years, and is preparing to do a stroke trial in China. In fact, the company has several projects in the works that will give it a significant presence in Asia as well as the United States.

"We have a fairly global ambition in terms of rolling out products and studies, and we're growing our infrastructure in that direction," says Garr.

Staking a claim
Growing stem cell market entices Big Pharma to harness its power for drug screening, toxicity testing
A roundup of North America's top five academic research institutions in the stem cell arena
Tools of the trade

Life science tool providers provide constant support to ever-evolving stem cell research community  

To view all of the content from our three-part series on stem cell research, click here  
Code: E091128



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