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Regenerative medicine is a tricky business, one that is still in its infancy. If you are an investor, you most likely acknowledge the upside present, but finding a good investment that instills confidence can be difficult in an industry as new as regenerative medicine/cell therapy. With that said, who better to talk to than Dr. Douglas Losordo?

Dr. Losordo may be the most decorated physician in the regenerative medicine space. Previously, he was the VP of New Therapeutic Development at Baxter (NYSE:BAX) where he and his team developed a cell therapy product that reached unprecedented endpoints (now in Phase 3), not to mention- he led big pharma to cell therapy. Now, he continues to work closely on the development of the space and in research, and I was thrilled that he took time from his schedule to discuss an array of cell therapy topics from a leading medical professional's point-of-view. Therefore, here is the revised transcript from what I consider a great interview, and an informative one for those who may be considering an investment, but aren't really sure of how to assess the space.

This interview highlights the success and knowledge of Dr. Losordo while celebrating his accomplishments in regenerative medicine, CD34+ development, and at Baxter.

Brian Nichols

At Baxter, as the VP of New Therapeutic Development, and now as part of the Scientific Advisory Board for both NeoStem and the "Stem for Life Foundation", you are very involved with close ties to the development of cell therapy. What was it that led you to cell therapy during a time when not many were exploring such medicine?

Dr. Losordo

As a post-doc in the lab of the late Jeff Isner, we were working on cardiovascular applications of laser technology. One day in our journal club we reviewed a paper in Science that described a pre-clinical study in which the damage from a heart attack was reversed by giving a growth factor to re-grow damaged blood vessels. The atmosphere in the room was one of shock and excitement bordering on disbelief - we had been taught that heart attack damage was irreversible, but this simple experiment directly and strongly challenged that concept. From that day on, the lab converted its focus completely to the concept of therapeutic angiogenesis, that is, the concept of stimulating the growth of new blood vessels for tissue repair.

Brian Nichols

It's kind of neat to hear how Baxter's Phase 3 cell therapy product was first developed, as an experiment. Adding on to this experience, you mention "therapeutic angiogenesis", what is it? Also, after "reviewing the paper" what was the next step of therapeutic development?

Dr. Losordo

Therapeutic angiogenesis is the foundation of all regenerative medicine, since any repaired functioning tissue needs a blood supply.

Five years after we reviewed that paper, one of the other post-docs in Jeff's lab, Takayuki Asahara, discovered the endothelial progenitor cell, or EPC for short, and showed that it was a naturally occurring repair cell. When we evaluated the therapeutic effect of these cells, we found a degree of repair that we had not seen previously. We have never looked back.

Brian Nichols

Today you are considered a great leader in the development of cell therapy. But when you first began, I imagine there was a bit of skepticism towards your decision to focus on something as unknown. Is this a fair assessment and have you seen a "shift" in perception, or how would this "shift" be reached?

Dr. Losordo

There is always skepticism when a new concept is introduced, and the regenerative medicine is no exception. There was tremendous resistance to the concepts of adult stem cell based therapeutics and to regenerative medicine. I once had a very well known scientist quip to me that any talk of regenerative medicine outside of the realm of developmental biology was a waste of time.

However, data ultimately carries the day and the weight of evidence mounts the skepticism [and] is giving way to excitement about the possibilities to treat diseases that have frustrated all other attempts.

Brian Nichols

You are probably most well-known for leading the development of a CD34+ cell therapy. If you would, please explain the significance of what you and your team accomplished with CD34+ cells including the time you spent at Baxter.

Dr. Losordo

After Jeff Isner's untimely death in 2001, I had to assume the leadership of the program that was working toward clinical application of EPC's. Drs. Asahara and Kawamoto and their teams had developed a cell culture method for enriching EPC's and the cells generated by this method worked well in pre-clinical models. However, when we talked to the FDA about the possibility of an early phase study, we began to understand the complexities and challenges of a culture-based method.

As an alternative we took advantage of the fact that the CD34 surface marker identifies a population of cells that is highly enriched with EPC's. Baxter had a technology to select CD34 cells, developed for use in the cancer field, FDA approved in 1999. Accordingly, we approached them in 2002 to see if they were interested in collaborating on the use of their device for the development of a cardiovascular therapy.

We conducted extensive pre-clinical studies that led to a phase I human clinical trial based at St. Elizabeth's Medical Center in Boston and also at Scripp's Green Hospital with Richard Schatz in La Jolla and the Minneapolis Heart Institute with Tim Henry.

After the successful completion of that study we moved to a phase II study in which Baxter took over the IND and I was national PI.

After the very encouraging results of the phase II study, showing improved exercise capacity and decreased chest pain in treated patients a decision was made to embark on phase III pivotal studies.

Along the way, many of my colleagues in academic medicine became interested in developing cell based approaches to cardiovascular disease and I was happy to help them by sharing my experience, IND's I had written, and so on.

Brian Nichols

I have been told that CD34+ cells are "the workhorses of regeneration". As someone who has studied the cells so thoroughly, what would you say are the possibilities of use with these cells in a therapeutic?

Dr. Losordo

No matter what type of tissue one is aiming to repair or regenerate, one uniform requirement is the need for a vascular (blood) supply. To date, the CD34 cell appears to be the most useful for vascular regeneration and repair. I want to be clear, however, that this was not our "invention". CD34 cells are naturally mobilized after injury and are naturally recruited to sites of tissue damage, so they represent one of the "first responders" of the body's defense system.

Brian Nichols

A lot of skeptics still point to the outcomes from the "TIME Study". They say that only 2.2% of participants responded to 3.3 million CD34+ cells. Last year, NeoStem (NASDAQ:NBS) found a threshold dose of 10 million cells. Therefore, do you think the TIME Study's failure was a result of it not using a large enough amount of cells? If not, then what happened in this study?

Dr. Losordo

I have a very different perspective on this matter. I would be puzzled if the outcome of every study using every different cell preparation and dose of cells was positive. That doesn't happen in drug development, so I'm not at all sure why the failure of one cell preparation should be considered evidence against all other types. It's worth noting that the cell prep used in TIME was, as far as I know, never tested in a pre-clinical model of myocardial infarction. I can't say why the study was negative, however, I do think it was a well done study that provides valid evidence that this particular cell preparation method at this dose was safe to administer but not effective.

The issue of dose is complex and is intimately link to the route of administration. Biologic agents, including proteins, antibodies and cells, are not like small molecule drugs and therefore exhibit different dose-response relationships. Often there is a "bell shaped curve" that describes the dose-response with increasing doses yielding increased response to a point, where the effect flattens or even drops off at higher doses. In cardiovascular cell therapy, there is evidence that this occurs with intramyocardial injections. However that peak-dose phenomenon has not yet been identified for intracoronary administration. On the other hand, pre-clinical studies provide evidence that there is a lower threshold dose below which no effect will be observed. This will be difficult to determine in human studies since the number of patients needed to precisely define dose-response in a clinical setting would be very high and probably not practical.

Brian Nichols

Currently, both Baxter, NeoStem and T2 Cure are developing therapeutics using CD34+ cells, and are using these cells on two different diseases. Obviously, your lab developed the use of CD34 cells for cardiovascular therapy which was then licensed by Baxter. But you are also quite familiar with NeoStem due to being on the company's scientific board. So what are the differences between these two specific therapies?

Dr. Losordo

Both Neostem and Baxter are using CD34 cells selected via an antibody coated magnetic bead. Neostem's approach involves aspiration of bone marrow while the approach we developed and brought to Baxter uses a drug to mobilize cells from the bone marrow followed by a procedure called apheresis to collect the cells from the circulating blood. In addition to the methods for collecting CD34 cells, Neostem is developing the therapy for patients with a heart attack and for those with heart failure, while Baxter's study is addressing chest pain that is not relieved by medication or surgery.

Brian Nichols

While the three therapies are different, it is easy for investors to point towards their similarities. All are being used in the cardiovascular space and are a form of cell therapy. With that said, what is the potential market for these two therapies (Baxter & NeoStem), and what is their importance to the future of CD34+ development?

Dr. Losordo

Cardiovascular disease is a very large public health problem worldwide. Acute myocardial infarction, congestive heart failure and refractory angina as well as lower extremity vascular disease, which can lead to the need for amputation, affect millions of people worldwide. The CD34 cell therapy approach holds significant promise for treating all of these conditions.

Brian Nichols

With NeoStem and Baxter's market potential, do you think big pharma and possibly government will gravitate towards the industry more so if both are successful in current studies?

Dr. Losordo

There is no question that there has been skepticism regarding the potential for cell therapy. I think that we are now at the point where the weight of evidence will start to overwhelm the skepticism and that more investment will be forthcoming, both from public and private sectors.

On the private sector side, I think there have been questions about the "business model", i.e. how does one make a therapeutic from a patient's own cells. However, there is a decades old example of this in the form of stem cell transplant for cancer treatment. In addition, as evidence mounts that cell-based therapies can benefit previously untreatable patients and keep them out of the hospital, it will be clearer how these therapies not only make medical sense but economic sense as well.

The latter point is what will, I believe, begin to drive substantial public sector investment in cell therapies. If, as the evidence is beginning to suggest, these therapies actually change the course of diseases that were previously thought to be unremittingly degenerative, then a new era of medicine will begin. I liken this to the dawn of the use of antibiotics: pneumococcal pneumonia was once a nearly uniformly fatal condition that is now often treated as an outpatient. I predict that we will one day look at heart failure the same way.

Brian Nichols

Both Baxter's CD34+ cell therapy and NeoStem's AMR-001 are also manufactured by PCT, a company owned by NeoStem. When you were at Baxter, why did you decide to work so closely with NeoStem on the development of your cell therapy?

Dr. Losordo

Neostem and PCT are world leaders in cell therapy and PCT has been spearheading the development of manufacturing practices for cardiovascular cell therapies. Therefore it was a perfect match with great synergy and mutual interest.

Brian Nichols

Finally, it must be noted that you have accomplished so much, whether it be hundreds of professional articles and abstracts used in research and in education, your development of the CD34 cell as a therapeutic for cardiovascular disease, or your work with NeoStem and the Stem for Life Foundation. So what's next for you, Dr. Losordo? What else do you hope to accomplish in regenerative medicine during your career?

Dr. Losordo

First I would like to accelerate the approval of as many cell therapies for cardiovascular disease as possible....the more patients we can reach and the more patients and their families who will be unburdened sooner, the happier I will be.

Second, I think we are in a changing time in which industry and academia and the public sector understand that we must collaborate to maximally benefit patients. Having been both in academia and industry I see an increased willingness to move in this direction and the recognition that this will be mutually beneficial. To the extent that I can facilitate this movement, I think it will ultimately be for the benefit of patients and society.

Third, I think it's critically important that patients and families and the public at large start to get a clearer picture of what I will call 'the stem cell revolution'. I think that when it becomes clear how adult stem cell therapies will positively impact society, the public will demand an increase in investment that will accelerate the field.

Conclusion

To be clear, there are very few if any in regenerative medicine that are as decorated as Dr. Losordo from a clinical perspective. In biotechnology, the goal is to determine whether or not a therapeutic will be effective in clinical trials and ultimately commercially. Dr. Losordo's is a good opinion to honor in this one particular segment of biotechnology. In cell therapy, we have therapies with massive market potential, very good data, and low valuations, which could ultimately produce large returns for shareholders.

Baxter is the first of big pharma to explore the space, and this was possible because of Dr. Losordo. He may not touch much on the investment side of a company, but if the goal is to determine if a product will be effective, then this is one person whose thoughts and insight should be weighed heavily.

Source: Interviewing Dr. Losordo: The Promising Development Of CD34 Cells