CEO Blog

Nick Colangelo

President and CEO of Aastrom

Nick joined Aastrom in 2013 with more than twenty years of executive management and corporate development experience in the biopharmaceutical industry, including nearly a decade with Eli Lilly and Company. Most recently, Nick was President and Chief Executive Officer of Promedior, Inc.  During his career, he has held a variety of executive positions of increasing responsibility in product development, pharmaceutical operations, sales and marketing, and corporate development.  He has extensive experience in the acquisition, development and commercialization of therapies to treat fibrovascular, metabolic and cardiovascular diseases.  During his tenure at Eli Lilly and Company, Nick held positions as Director of Strategy and Business Development for Lilly’s Diabetes Product Group and also served as a founding Managing Director of Lilly Ventures. Nick received his B.S.B.A. in Accounting, Magna Cum Laude, from the State University of New York at Buffalo and a J.D. degree, with Honors, from the Duke University School of Law.

Insights into DCM and the ixCELL-DCM Trial

June 12th, 2013

During our first-quarter earnings call last month, I was pleased to report that we began treating patients in the ixCELL-DCM Phase 2b trial, which is evaluating ixmyelocel-T for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy (ischemic DCM). This clinical trial offers a potentially historic advancement in the treatment of patients with advanced heart failure due to ischemic DCM, an indication for which we have an orphan drug designation in the United States.

DCM is a condition in which the heart becomes weakened and enlarged and cannot sufficiently pump blood throughout the body. DCM is the third most common cause of heart failure and the most frequent cause of heart transplantation. A majority of the advanced heart failure patients who no longer respond to medical therapy — more than a quarter of a million patients in the U.S. — have DCM, and approximately 60% of these cases are of ischemic origin due to prior heart attacks or atherosclerosis. These patients typically have maximized their use of prescription and device therapies, and are no longer candidates for procedures to restore blood flow such as angioplasty and bypass surgery. At this stage of the disease, they have very limited treatment options, which generally include placement of left ventricular assist devices and heart transplantation.

What makes advanced heart failure due to ischemic DCM so challenging for patients is its impact on daily life. The condition significantly reduces exercise capacity and quality of life, because for many patients, walking even a short distance causes severe shortness of breath and fatigue. There is a strong rationale for developing ixmyelocel-T for the treatment of ischemic DCM. In preclinical studies, ixmyelocel-T was found to significantly reduce cardiac tissue damage and demonstrated additional cardioprotective effects in relevant disease models. In Phase 2a clinical trials, ixmyelocel-T was found to be well-tolerated and demonstrated positive efficacy trends, including improved symptoms and improved walking distance in treated patients compared to placebo.

The ixCELL-DCM Phase 2b trial is designed to enroll 108 patients at about 30 sites in the U.S. and Canada. This is a double-blind, placebo-controlled trial that will primarily measure mortality, hospitalizations, and heart failure emergency room visits in trial participants. The trial also will examine a range of clinical, functional, and symptomatic measures. The study is on track to complete enrollment by the end of Q1 2014 and show top-line results in Q2 2015.

Aastrom is one of the few companies working to develop a treatment for this major unmet medical need, and our clinical research program for ixmyelocel-T is one of the most advanced global research efforts in regenerative medicine. As we continue to make progress, we look forward to the opportunity to share our results and insights with patients, physicians, and researchers around the world.

Regards,

Nick Colangelo

Not All Cell Therapies Are the Same

May 6th, 2013

As my colleagues at Aastrom participate in important medical meetings on regenerative medicine and cellular therapy, we can see why 2013 has been named the “Year of the Stem Cell” by The Atlantic magazine.  The medical community is excited about the therapeutic potential of regenerative medicine and our unique multicellular product candidate ixmyelocel-T is attracting great interest as a promising new treatment modality for serious cardiovascular diseases such as advanced heart failure due to ischemic dilated cardiomyopathy.

It is well understood that there are multiple cell populations and multiple signaling pathways involved in the disease progression involving tissue injury, chronic inflammation, and the resulting tissue damage that leads to loss of organ function, as well as the processes involved in the repair and regeneration of damaged tissue.  Therapeutic approaches targeting single signaling pathways in these complex disease and repair processes have not proven effective, and most cell therapy approaches expand a single cell type to attempt to arrest manifestations of the disease.  Aastrom is taking what we believe is a highly differentiated and superior therapeutic approach by developing multicellular therapies that utilize an expanded population of the key cell types that the body naturally uses to repair and regenerate damaged tissue.

Ongoing discovery research by Aastrom scientists and our outside collaborators continues to define the mechanism of action of ixmyelocel-T and differentiate our product from other cell therapies based on the activity of the two key cell populations in ixmyelocel-T:  mesenchymal stromal cells (MSCs) and M2-like anti-inflammatory macrophages.  These key cells have multiple direct activities and beneficial effects on nearby cells that have been shown to promote tissue repair and regeneration by reducing inflammation and promoting angiogenesis and remodeling of damaged tissue.  Based on the activities of these cells and the resulting therapeutic effects, Aastrom’s unique multicellular therapy platform offers the potential for multiple therapeutic applications in treating cardiovascular and other fibrovascular disorders of the lungs, liver, kidney and other organs.

There is enormous therapeutic potential for ixmyelocel-T based on its multicellular composition and the promising results in the treatment of ischemic or damaged tissue demonstrated in preclinical and clinical studies conducted to date.  We look forward to generating results in our current ixCELL-DCM phase 2b study of ixmyelocel-T for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy, and continuing to explore the potential therapeutic effects of ixmyelocel-T to repair and regenerate damaged tissue in other severe diseases.

Regards,

Nick Colangelo

The Next Chapter for Aastrom

April 4th, 2013

Our recent decision to implement a strategic change in our R&D programs to focus on the development of ixmyelocel-T for the treatment of dilated cardiomyopathy (DCM) and stop enrollment in the Phase 3 REVIVE trial in critical limb ischemia (CLI) reflects the significant opportunity that we see to treat advanced heart failure caused by DCM and the challenges that we faced in enrolling the REVIVE study in a reasonable timeframe.  While we believe that ixmyelocel-T has strong therapeutic potential to treat CLI, based on previous clinical results showing that ixmyelocel-T was efficacious and well-tolerated in this patient population, the decision was based on our need to allocate resources to advance ixmyelocel-T toward commercialization as quickly as possible.  We believe that the DCM program represents our best near-term opportunity to accomplish this goal.

Our previous results in DCM —in both preclinical and clinical studies — suggest that our patient-specific multicellular therapy can produce a range of clinical benefits for patients with severe heart failure whose limited treatment options include heart transplantation. Read More…

The Evolution of Cell Therapy

March 1st, 2013

As clinical stage research involving stem cells has expanded during the past decade, so has public debate regarding the relative advantages and disadvantages of embryonic versus adult stem cells.  Ethical concerns about the use of embryonic stem cells have dominated much of this discussion. Recently, attention has shifted toward efforts to make adult stem cells more versatile and share more of the advantages of embryonic cells, which can differentiate into any human cell types.

Researchers have made important advances in their ability to manipulate adult cells.  For example, scientists from the University of Cambridge’s Institute for Medical Research reprogrammed skin cells to behave like liver cells so that we can better understand the mechanisms of different liver diseases and more easily identify optimal targets for therapeutic drugs. While these efforts may open up new avenues of research, there have been some challenges in administering these cells in humans. Studies have found that the reprogramming process in adult stem cells may increase the risk of tumors. In some cases, reprogrammed cells appear to retain the memory of their original cell activity, which could make their behavior unpredictable. When researchers at the Children’s Hospital in Boston tried to transform blood cells into tissue cells, they reverted back to blood cells soon after.

Read More…

The Promise of Cell Therapies in Cardiovascular Disease

February 1st, 2013

Dear Friends of Aastrom,

February is American Heart Month, and it is during this time that we recognize many of the important advances in medical research that may help us prevent and treat cardiovascular disease more effectively. In recent years, breakthroughs in surgery, drug therapy and devices have expanded options for patients, making it possible to lower the risk of a cardiac event and treat the effects of peripheral artery disease (PAD). Despite these advances, cardiovascular disease remains the leading cause of death in the United States. Each year it disrupts the quality of life of millions of people and is the cause of approximately 160,000 amputations and 1.5 million heart attacks in the U.S.

Fortunately, there are reasons to be optimistic. Recent advances in regenerative medicine and cell therapy are encouraging and have shown the potential to improve the lives of patients with the most severe forms of cardiovascular disease. In preclinical and clinical studies, cell therapies have demonstrated the potential to repair damage to the heart muscle and other vascular tissue that can occur with a cardiac event. They also have the potential to help restore blood flow or repair genetic defects. If we continue to make clinical progress in this area, cell therapies may become an effective, less costly treatment option for people with advanced cardiovascular disease. Read More…

New Year, New Opportunities at Aastrom

January 1st, 2013

Dear Friends of Aastrom,

As the new interim chief executive officer of Aastrom Biosciences, I am honored to lead the company as we continue to advance the clinical research programs for our lead product candidate, ixmyelocel-T.  I believe we have a unique opportunity to improve the lives of people with severe, chronic cardiovascular diseases with ixmyelocel-T, and am very pleased to have the opportunity to bring my experience building successful pharmaceutical brands to this development program as we begin to formulate plans related to commercialization.  Since I joined Aastrom in August as chief commercial officer, I have seen firsthand the potential of our technology to treat these diseases and the dedication of our team to bring this promising therapy to patients who may benefit from it. Read More…

A Commitment to Transparency

December 1st, 2012

Dear Friends of Aastrom,

Aastrom’s commitment to transparency was reinforced by the recent announcement from GlaxoSmithKline (GSK).  GSK made headlines when it announced a new policy to disclose all clinical data from the company’s drug development programs.  Previously, the company had followed prevailing industry standards by releasing results from only some of its clinical studies (generally, only the positive ones).  A 2008 study[i] by the University of California, San Francisco found that many drug companies do not routinely report negative clinical data, while some do not make any data available to the public.  We welcome GSK’s initiative – it is good clinical practice and consistent with our commitment to transparency at Aastrom.  This move toward greater transparency is an important trend with profound implications for the future of research.

We believe that the benefits of disclosing all clinical results, not just the positive study results, far outweigh the real or perceived risks.  Full disclosure allows any interested party to review all of the potentially relevant data about experimental therapies.  This allows for a much broader and more accurate assessment of both safety and efficacy – the mechanisms of action – and also enables scientists and physicians to identify potential areas for future research.  When publicly available information is incomplete, it can lead the medical community to flawed conclusions that may limit the chances of future clinical success or, in extreme cases, actually cause patients harm.

Read More…

Ixmyelocel-T: From Product Candidate to Product

November 1st, 2012

Dear Friends of Aastrom,

There have been many studies over the years highlighting the fact that drug discovery and development is typically a very long, risky, complex and costly process.  It is not uncommon for drug development programs to last a decade or more, beginning with early-stage discovery and research, and progressing through late-stage clinical development, regulatory review and approval.  Within that timeline, companies must continually monitor progress and determine when and whether to expand their focus to include essential commercialization strategies to prepare to bring promising late-stage product candidates to the patients who need them.

Over the past year, Aastrom has initiated a number of important activities to support the future commercialization of ixmyelocel-T, which is currently in Phase 3 clinical trials for the treatment of patients with severe peripheral arterial disease (PAD) and existing tissue loss, and in Phase 2 trials for the treatment of patients suffering with dilated cardiomyopathy (DCM). Read More…

Regulation in Regenerative Medicine: Patient Safety Has to Come First

October 1st, 2012

Dear Friends of Aastrom,

In July 2012, after several companies had been treating patients with unapproved stem cell therapies, the U.S. District Court in Washington affirmed the right of the FDA to regulate therapies made from a patient’s own stem cells. I believe this is a good decision that will protect patients, strengthen our industry and ensure the safety and therapeutic value of approved products.

The move to introduce appropriate oversight and regulation of cell therapy comes as no real surprise – the number of authorized cell therapy clinical trials has increased steadily in the U.S. over the past 10 years, from 12 trials initiated in 2001 to more than 50 trials initiated in 2011. While certain aspects of the U.S. regulatory process might be considered burdensome, I believe it is imperative that stem cell therapies be tested rigorously and to the highest standards. The fact that cell therapies are derived from cells found in the body does not eliminate this responsibility. Regenerative medicine has transformational potential, but that does not necessarily mean that each cell therapy technology or product will result in a safe and effective therapy.

Clinical trials often identify unexpected and unanticipated safety issues. Rigorous clinical trials also often find that some proposed products are not as efficacious as they need to be to balance their risks. For example, only one in four biologic treatments has ultimately proven to be both safe and effective, according to a BioMedtracker study. Marketing any therapy – for cancer, heart disease or any other disease – that has not been proven to be both safe and effective in rigorous clinical trials puts patients at risk and ultimately hurts all research organizations working to develop new therapies. Read More…

Investing in Cell Therapy

September 5th, 2012

Dear Friends of Aastrom,

Discovering, developing and launching new medicines is a challenging enterprise, often requiring more than a decade of pre-clinical and clinical research and an investment in the tens  or hundreds of millions of dollars.  And the harsh reality is that only about one in ten drugs that reach clinical stage development eventually win FDA approval.  Despite these long odds, the biotechnology industry has continued to flourish, even though many traditional sources of capital, such as venture firms, are shrinking and new sources of capital are needed.  What does all this mean for the future of cell therapy and companies like Aastrom that are focusing on promising but complex cell therapies?

Many of the risks inherent in drug discovery and development are magnified in cell therapy because the field is relatively young, the science behind it is still emerging and few cell-therapy products have been approved.  However, with each clinical and regulatory success, the therapeutic potential of cell therapy becomes more apparent and investor sentiment improves.  As a result of recent progress, interest in regenerative medicine is now growing steadily, the number of cell-therapy clinical studies is increasing and capital is flowing toward a few companies with the most promising and late-stage development programs.

Aastrom has benefited from these trends and emerged as a leader in cell therapy because we have focused on compelling applications of our proprietary technology in terms of medical need, clinical rationale and commercial opportunity. Read More…

Communicating Progress

August 1st, 2012

Dear Friends of Aastrom,

As investors and the media continue to follow the progress of stem cell therapy companies, the need for clarity and transparency about our work is growing. We welcome this trend and the responsibility it places on us to describe clearly, openly and on a regular basis what we do.

Over the past year, we have found that investors, clinicians, patients and advocates are most interested in our answers to three key questions:

1. Why do you believe Aastrom’s stem cell therapy will work more effectively than other methods of treating disease?

2. What makes critical limb ischemia (CLI) an appropriate target for Aastrom’s stem cell therapy?

3. When will a large pharmaceutical company embrace stem cell therapy and partner with Aastrom?

The answer to the first question is that bone marrow cells have been used safely and effectively for over 30 years to fight certain diseases. Our stem cell therapy is produced from each patient’s bone marrow. Certain cell types found in and expanded from bone marrow – especially the CD90+ mesenchymal stromal cells and the CD14+auto+ M2 macrophages that comprise the majority of our stem cell therapy – have been shown to support tissue remodeling, address chronic inflammation and promote angiogenesis. No other stem cell therapy has this unique combination of cells. Based on compelling preclinical and clinical results, we believe that delivering our stem cell therapy directly to damaged tissue has therapeutic effects for CLI patients that are not possible with other treatment methods such as open surgical procedures, endovascular devices or traditional pharmaceuticals. Our clinical results thus far provide strong support for this conclusion.  Read More…

Targeting Dilated Cardiomyopathy: A Rapidly Progressing Condition with No Cure

July 5th, 2012

Dear Friends of Aastrom,

Dilated cardiomyopathy (DCM) is a progressive disease of heart muscle. It is now the third most common cause of heart failure, which affects approximately 4.9 million people in the United States (www.americanheart.org). Dilated cardiomyopathies are associated with both systolic abnormalities (difficulty of the left ventricle to empty or eject blood from its chamber) and diastolic abnormalities (increased resistance to filling of one or both ventricles). The progression of DCM can be rapid; studies have found that 50 percent of the deaths from DCM occur within two years of diagnosis (http://health.usnews.com).

Currently, there is no cure for DCM, but cardiac medications, lifestyle changes and implantable devices can help to control some symptoms.  When these treatment options can no longer control symptoms of DCM, heart transplantation may be the only option for many patients – in fact, DCM is now the most frequent cause of heart transplantation (www.americanheart.org).  Unfortunately, there are only enough donors for about 2,000 heart transplants each year.  More than 95% of patients with moderate or severe heart failure (NYHA Class III or IV) will not be able to get a transplant. (Zacks)

One sign of hope is research showing that mesenchymal cells, monocytes and alternatively activated macrophages can have a positive impact on heart muscle and function damaged by DCM. Read More…

Thoughts on Leadership

June 4th, 2012

Dear Friends of Aastrom,

Whenever I am asked what makes Aastrom a leader in cell therapy, I usually begin my answer by citing the evidence of our leadership.

During the past year, we have demonstrated the therapeutic potential of our unique product to treat cardiovascular diseases for which there are no other approved therapies.  We have validated and expanded our efficient, proprietary, high-margin, state-of-the-art cell-production technology.  We have launched the largest and most advanced clinical research program in critical limb ischemia and attracted significant new capital from institutional investors.  These achievements reflect the enormous progress we have made to advance our unique cell therapy into late-stage clinical development.

The qualities that make Aastrom a leader take longer to describe but they are no less important to understanding why we have been successful.  They include how we work, the values we uphold and the company we keep.

How we work at Aastrom is a reflection of our unique corporate culture and the talented team we have assembled.  We are not unique among biotechnology companies simply because we work hard and believe in what we do.  We are unique because we have skills and experience unlike any other company and bring unwavering dedication to our mission.  As a result, we have identified important unmet medical needs and markets where our technology can best be applied – and we have moved rapidly to address these new opportunities.  Read More…

The Critical Role of Clinical Trial Investigators

May 21st, 2012

Dear Friends of Aastrom,

Planning and executing a clinical trial requires a monumental effort with careful planning and coordination at every stage. But it always starts with a fundamental need – a team of clinical investigators and staffs who will coordinate patient screening and care, and also handle the necessary record keeping and reporting to support regulatory submissions.

In our experience at Aastrom, working with experienced and dedicated investigators provides us with essential support in the earliest stages of our planning for clinical trials. Our investigators contribute important insights and recommendations related to study design planning and methodology. We work to establish clear and open lines of communication right from the start, and maintain those open channels at every stage as the trial advances to completion.

In our clinical research thus far, we have been privileged to work with many of the leading clinicians and practices in the treatment of critical limb ischemia (CLI) and dilated cardiomyopathy (DCM). CLI is the most severe form of peripheral arterial disease (PAD) caused by chronic inflammatory processes associated with atherosclerosis that result in markedly reduced blood flow to the legs, feet and hands. There are an estimated 10-12 million people with PAD in the United States and over 1 million people with CLI. Read More…

Targeting CLI: A Major Unmet Need for Patients and a Significant Opportunity for Aastrom

April 24th, 2012

Dear Friends of Aastrom,

Over one million people in the U.S. are living with critical limb ischemia (CLI), a severe form of peripheral arterial disease (PAD).  CLI is a devastating and often fatal disease where blood flow to extremities is restricted, resulting  in debilitating pain, life-threatening infections, loss of limbs, and death. There are currently no FDA-approved therapies to treat CLI; the most frequent treatment option is revascularization surgery to restore blood flow to affected areas.  However, all too often, especially for very ill CLI patients, revascularization surgery is not effective.  At Aastrom we are applying our proprietary cell-processing technology to develop an entirely new approach to the treatment of CLI. Read More…

A Welcome Endorsement: Aastrom Receives New $40 Million Investment

March 9th, 2012

Dear Friends of Aastrom,

The financial turmoil of the past three years has made fundraising especially difficult for capital-intensive biotechnology companies that must rely on investors or partners to fund their operations and keep promising development programs on track.  During this period of economic uncertainty, we have seen venture capitalists, institutional investors and pharmaceutical companies shift their risk tolerance in favor of proven technologies (i.e., small molecules and antibodies) and later-stage product candidates.  There are also fewer of these investors compared to several years ago, which has made it more difficult for companies with novel technologies and/or earlier-stage programs to raise capital or partner on reasonable terms.

 During the past few years, we have seen many biotech companies be forced to raise money by selling their stock at a significant discount and by issuing warrants worth 50 to 100 percent of the stock being purchased.  These discounts and warrants are effective in attracting certain investors to fund a company’s operations.  However, they are very expensive inducements and, as we have found, often have long-term negative consequences for existing investors.  Read More…

Stem-Cell Therapy and Patient Safety – The Source Matters

February 6th, 2012

Dear Friends of Aastrom,

The issue of safety associated with stem cell therapies has been in the news recently. Last month, the FDA issued a consumer update describing potential risks associated with the use of stem cell therapies that have not yet been approved. Also recently, 60 Minutes ran a story about patients with severe illnesses who sought treatment with unapproved stem-cell therapies when no approved treatment options were available. In many cases, these patients paid vast sums of money and traveled to other countries to be treated with potentially dangerous and unregulated cell therapies.

These reports highlight the value of appropriate safety standards in the development of cellular therapies, standards which Aastrom maintains in all of its development, manufacturing and shipping procedures. These stories also raise an important issue about the different types of stem cells used in medical research and drug development, and the need to define clearly which cell types are being used. In many cases, the ethical or safety concerns associated with cell therapies relate to the use of embryonic stem cells, not the use of adult or autologous (“patient-specific”) stem cells which we use at Aastrom. Therapies derived from non-embryonic stem cell therapies are now approved for use in treating more than 70 medical conditions. 1, 2

In the development of our cellular-medicine product, Aastrom uses the patient’s own bone marrow, which is collected in an outpatient setting. After the sample arrives at our laboratory in Ann Arbor, each step of the production process is carefully monitored to meet or exceed the safety and quality standards established by the FDA. Read More…

Unlocking the Potential of Regenerative Medicine

January 17th, 2012

Dear Friends of Aastrom,

Regenerative medicine is the term most often used to describe research and drug development involving the use of stem cells to stimulate the body to rebuild and repair damaged tissue.  Based on the results of multiple research programs in the U.S. and other countries, regenerative medicine has the potential to cure or reverse the symptoms of many diseases that affect different tissues in the body, including vascular, muscle, organ, bone and nerve tissues.

Today, the field of regenerative medicine encompasses many approaches to treatment, including:

  • therapies administered by injection to promote tissue healing and organ regrowth;
  • the growth of new tissue and organs in a laboratory for implantation in patients; and
  • the use of biocompatible materials or small molecules to support the body’s natural ability to regenerate tissue.

At Aastrom, our approach to regenerative medicine is to use a patient’s own cells to develop a therapy that includes the optimal range and ratio of cells to treat severe, chronic ischemic cardiovascular diseases such as critical limb ischemia (CLI) and dilated cardiomyopathy.  The product we are developing, ixmyelocel-T, is personalized and custom-made for each patient from a small amount of his or her own bone marrow cells.  Read More…

Aastrom Nearing Launch of Phase 3 Revive Clinical Trial for Critical Limb Ischemia

December 9th, 2011

Dear Friends of Aastrom,

As you may have noticed, we recently redesigned the Aastrom website to help visitors access more information about our company. We hope this redesign makes it easier to learn about our work, mission and progress. To support the new site, we are also introducing a new blog about Aastrom where we will offer perspectives on important issues associated with our work and industry. I am very pleased to begin this new series with some comments on the disease that has been a primary focus of our work and research at Aastrom for the past several years—critical limb ischemia (CLI). (Learn more about critical limb ischemia or Aastrom’s CLI clinical trials, or watch the Living with CLI video.)

The importance of our CLI program cannot be overstated, as the need for a new treatment to help the millions of people affected by this terrible disease has never been greater. Read More…