Holaira, Inc. (formerly Innovative Pulmonary Solutions, Inc.)
located in Minneapolis, Minnesota is a privately held lung denervation
company developing minimally invasive products to make breathing easier for
patients suffering from obstructive lung diseases. Founded in 2008, Holaira
is currently working on a novel catheter-based system that has the potential
to improve lung function, exercise capacity and quality of life for patients
with chronic obstructive pulmonary disease.
President & CEO
Dennis Wahr, M.D.
joined Holaira in September 2012, with a unique background in serial medical
device development, clinical evaluation and commercialization experience.
Prior to joining
Holaira, Dr. Wahr co-founded Lutonix in 2007 and served as its President and
CEO until CR Bard acquired the company in December 2011. Preceding its
acquisition, Lutonix developed a unique drug coated balloon angioplasty
technology for the treatment and prevention of vascular stenosis caused by
atherosclerosis. Prior to Lutonix, Dr. Wahr co-founded Velocimed in 2001,
and served as its President and CEO until its acquisition by St. Jude
Medical in 2005.
As a company CEO,
Dr. Wahr has wide-ranging experience with both the European regulatory
authorities and the US FDA. His companies have sponsored 9 clinical trials
involving more than 1500 patients leading to approvals for 4 unique and
innovative medical products.
Dr. Wahr has
served on the board of directors of several medical device companies
including Accumetrics, IDev, Velocimed, and Lutonix, and he currently serves
as chairman of the board for Intact Vascular. Additionally, Dr. Wahr spent
two years as a Managing Director with RiverVest Ventures focusing on capital
investments in emerging medical technology companies.
Dr. Wahr received
a Bachelor of Arts from Albion College and his Medical Degree from Wayne
State University School of Medicine. He did a fellowship in interventional
cardiology at the University of California, San Francisco and is currently
board certified in interventional cardiology. He spent more than 14 years in
clinical practice and served as the Chief of Cardiology at the Michigan
Heart and Vascular Institute in Ann Arbor, MI prior to launching his
Interview conducted by:
Lynn Fosse, Senior Editor, CEOCFO Magazine, Published – November 3, 2014
Dr. Wahr, what is the concept behind Holaira?
developing a novel catheter-based system to treat COPD.
How does it work?
We have a
specialized dual cooled RF energy catheter, introduced through a standard
bronchoscope that delivers targeted energy to ablate the parasympathetic
nerves in the walls of the right and left main stem bronchi. Consequently,
the airways are dilated and air can flow more easily to the lungs, enabling
the patient to breathe more easily.
What are you doing to the nerves when you are disrupting them?
ablating the nerve. Nerve tissue, heated above about 65 degrees centigrade,
ceases to function.
Would this be a one-time procedure?
We believe it
is a one-time procedure. In our first two clinical studies and registries,
the effect was sustained through the one-year follow-up. Subsequently, we
expect the effect to be permanent. This will be validated with two to three
year follow-up data.
CEOCFO: Has a similar process been tried
No, this is a
completely novel therapy. We are disrupting nerves in the main stem bronchi,
and that is like cutting an electrical wire. The effect of this extends
throughout the whole lung field. That is where the company name comes from:
Hol-air-a, which means air flowing to the whole lung.
Why did you think it would work?
of action here is well known. COPD is treated today with pharmacologic
therapy. The most common form of pharmacologics for COPD is a class of
inhaled drugs called anticholinergics, like Spiriva™. These drugs target the
parasympathetic nervous system, which controls the motor function that
causes the airways to constrict, making breathing difficult. The drugs work
by temporarily blocking the neurotransmitter, called acetylcholine, from
reaching the constricted smooth muscle. This causes the smooth muscle in the
airway to relax and the airway to open, making breathing easier. The
inventor of this technology, Dr. Martin Mayse, is a pulmonologist himself
and was aware of this mechanism of action. He had the great idea that if you
just disrupt these nerves when they enter the lungs, you might be able to
achieve a permanent sustained effect and get away from some of the
disadvantages of inhalers.
Where are you in the development process today?
completed multiple preclinical studies and two multicenter human feasibility
studies. Both of the feasibility trials were conducted outside the United
States, and data from those studies were presented at the European
Respiratory Society meeting for the first time in September of this year. We
expect a comprehensive paper will be coming out shortly in a peer-reviewed
journal. We are now moving forward with a phase 2 trial, which we call
AIRFLOW-1. AIRFLOW-1 is a two phased randomized trial with a sham control,
designed to help us better understand two things. The first goal is to
determine the optimal dose of energy to get the best result. The second is
to compare results in those who undergo the actual procedure with those who
have the sham procedure.
How is the procedure done?
is done with the patient lying on a standard bronchoscopic examining table.
While currently done with general anesthesia, in the future we believe it
will be preferable to use conscious sedation. An interventional
pulmonologist puts a standard flexible bronchoscope down the patient’s
airway through the trachea, and once that is placed our catheter is inserted
through the working channel of the flexible bronchoscope. It is possible to
treat both main stem bronchi in a single procedure. A procedure takes less
than an hour to complete.
How do you measure the results both immediate and ongoing?
endpoints are very well understood for this type of therapy because they
have been used for decades in pharmaceutical trials. They consist of three
main areas. The first is to measure improvements in lung function using
pulmonary function tests. That is where patients breathe into a machine that
can precisely measure and quantitate lung function. The second area is
exercise capacity or endurance, where you test the patient’s physical
abilities in a quantitative way using cycling or walking tests. The third
area is quality of life. There are well-validated questionnaires that
patients fill out, which allow us to assess whether or not the patient is in
fact having a better quality of life compared to before the therapy.
CEOCFO: What types of patients would be candidates
for the procedure?
include criteria for patients with moderate to severe COPD. This is a very
large patient group. It includes both patients with emphysema and chronic
bronchitis. Both types of patients are potentially eligible for the therapy.
almost anyone with COPD?
patients in any clinical study have to go through a checklist of
inclusion/exclusion criteria. You try to identify patients that do not have
other associated diseases that could complicate the ability to study your
effect on a disease. I would not say that anybody who shows up gets included
in the study, but the potential pool of patients for this study is very
large. Globally, there are over 190 million people estimated to have COPD,
and at least 15 million of those are in the US. Another 20 million are in
Europe. There are a lot of people suffering from this disease.
What did you learn from the initial test that may have changed what you are
In our first
two feasibility studies we learned a couple things. We learned that the
procedure appears to be safe. That was the first priority. The second was
that we have a preliminary signal that we can improve lung function. Those
were the two key things. We also learned, like you always do in early stage
medical device development, small nuances of the device that we could modify
to make it more user friendly and potentially more efficacious. After
treatment, we followed up with the patients for one year. We took advantage
of that one year to design and develop a second generation device, which is
now being used in our AIRFLOW-1 study.
CEOCFO: What attracted you to Holaira?
When I was
called by the company to solicit my potential interest in becoming the CEO,
I went in with no preconceptions. I had not been in the pulmonary field
before, but when I look at medical technology I always start with how big is
the problem being solved, the unmet clinical need. COPD is actually one of
the larger and more serious unmet clinical needs in medicine today. The
benefits that patients get from pharmaceutical therapy are temporary. There
exists a stunningly huge opportunity to help millions of people. That was
the first thing. The second thing that attracted me was the realization that
the mechanism of action was very clear. The Holaira technology appeared to
be an elegant solution and I could easily understand how this therapy might
work. Realizing how much potential benefit could come from this type of
therapy and the fact that I could understand the mechanism of action, I
could not resist jumping in to help bring this to life.
CEOCFO: Are you funded for the next steps you would
like to take?
Yes. In April
of this year we closed a $42 million Series D financing round, which will
fund AIRFLOW-1, our phase 2 clinical trial, and continued development of our
technology platform. This should carry the company through the end of 2016
and into the first part of 2017. At that point, we should have one year
follow-up on our AIRFLOW-1 patients. One-year follow-up data for a
randomized trial will be a key milestone. Additionally, we anticipate
obtaining our CE mark during this time period, which will provide us the
potential to commercialize should we choose to.
Has the medical community been paying attention or is it too early?
that you should not raise hype, and that’s why we held off doing any type of
public introduction of our technology until last month’s scientific
presentations at the European Respiratory Society Congress in Munich. That
was really our first coming-out. We held off until we had at least one year
follow up on all the patients in the feasibility studies. I believe that the
data was well received by the pulmonologists who attended the meeting.
What else have you learned through past experience that is helpful in going
from creation or development to commercialization?
that in the medical device industry you need to make sure you have a
profound understanding of your device, its safety profile, and how to
optimize its treatment effect before jumping into a pivotal trial. For this
reason, we are taking a little bit different approach than what medical
device companies have typically done in the past where they have jumped from
small feasibility trials straight to the pivotal trial and then learned
things in the pivotal trial that they wished they had known sooner. I
actually believe the device industry should do product development more like
the pharmaceutical industry does with a three-phase clinical development
program. It takes a little bit longer, and it probably adds a
year-and-a-half to two years to the overall timeline, but I think it is
safer for the patients and it greatly enhances the potential for developing
a product that has meaningful benefits for the patients.
Are there any potential side effects that you have seen so far?
No, we have
been very happy with the safety profile of our product so far. This is not
by chance. We have conducted a large pre-clinical animal program to make
sure we understood the treatment effect of our specialized RF ablation
technique and the optimal energy dose. If you under-dose it, you might not
get a treatment effect. On the other hand, you do not want to use too much
energy because, similar to ablation techniques anywhere in the body, safety
can be compromised. We have been very careful about that.
CEOCFO: Will you be looking at potential
companies need to develop their products from the perspective that they are
going it alone. The practical reason is that you do not get to choose when
to sell the company. The buyers are the ones who get to make that choice.
The practical way to manage a company and product development is to expect
that you will need to be self-reliant. Avoid the temptation to cut corners
and, instead, build a strong foundation that will both enhance your chances
of success and make you more attractive to potential acquirers. Sometimes
partnerships can be very helpful, but we are not making that an essential
part of the business plan.
Put it all together for our readers. Why does Holaira standout?
I think it is
the most exciting opportunity in medical devices today because the therapy
has the potential to have a very clinically significant treatment effect for
a huge number of patients. On top of that, we have the potential to lower
the overall costs for their medical care worldwide. COPD patients are very
expensive patients. In fact, the US alone spends about 50 billion dollars
annually on the treatment of COPD, with similar numbers in Europe.
Worldwide, of course, it is even bigger. The most expensive part of the care
of COPD patients is treating exacerbations, where they suddenly have a
flare-up in their lung function and wind up being seen in the emergency room
or admitted to the hospital. These are extremely expensive readmissions, and
a truly effective therapy for COPD has the promise or the potential to lower
the readmission rates to hospitals. If that is the case, this is that
perfect situation where you could deliver a great clinical benefit to the
patients while saving the health care system money, which I think is
something that is very exciting.