The Science of a Stronger Heart... Robert Blum, CEO, CytoKinetics
If you're alive, your heart is beating, and there's no doubt you have to keep it that way and for a very long time. One South San Francisco company, Cytokinetics, is focused on many aspects of doing exactly that. Robert Blum is its CEO. Robert, welcome to Biotech Nation.
Robert Blum:Thank you. Nice to be here. Thank you.
Dr. Moira Gunn:Now essential equipment for all human life is that we have hearts, and these hearts have to keep beating. And as with everything, there are the genetic cards we are dealt as important as the life we have lived and how it affects it. Now cytokinesis is focused on conditions of the heart and to frame this I'd like just to make an early note for the listeners that you have drug candidates in the last phase, that's phase three, one with a successful readout as we say, a successful data outcome and you're waiting for the FDA's final say in December as of this recording and those on the inside would call this a PDUFA date, but December is the go no go date from the FDA like bring it to market or we might want something else. Very exciting time for you. But cytokines also has a drug candidate in phase two and another one in phase one and even more preclinical and research.
Dr. Moira Gunn:So there's a lot of shots at a lot of goals here at this point all having to do with the medical conditions of the heart. So let's start remembering the heart is a muscle which pumps blood through veins, keeping blood circulating throughout our bodies. Let's start with conditions of the heart, and first off, I'd like to hear about heart failure. What is heart failure?
Robert Blum:Heart failure is the number one reason why people over the age of 65 in this country are hospitalized. It's the number one driver of Medicare costs, and our company has been focused in this area for many, many years. Cytokinetics is celebrating its twenty seventh year since we formed this company back a while ago, and our scientists are pioneers and leaders in understanding the mechanics of how heart muscle pumps blood for the benefit of patients, and how we can address syndromes of heart failure by enhancing the pumping function or suppressing the pumping function depending on what may be the underlying problem. There are forms of heart failure where your heart is impaired and can't pump enough blood. There are forms of heart failure where your heart is hyperactive and contracting to a too great an extent, and the therapeutic objective is to suppress the hyper contractility.
Robert Blum:So our scientists are experts in the mechanics of heart muscle pumping function, and we've developed potential medicines that either activate or inhibit the protein that drives the force production of your heart. And this has been the benefit of quite a long story, long history of research and development, but we're very excited. The first amongst these potential medicines is sitting in front of the FDA awaiting a potential approval later this year for a form of this disease called hypertrophic cardiomyopathy, and Already as you've mentioned, we've seen clinical trial results and evidence that suggest that a cardiac myosin inhibitor, a cardiac muscle inhibitor, can increase exercise stamina and relieve the burden, the symptom burden for these patients. What's happening with this disease, absent a treatment such as this, is patients are short of breath. They're having difficulty climbing stairs, walking to the end of the driveway.
Robert Blum:These are patients that live with the looming threat of sudden cardiac failure, so this creates not only a cardiac syndrome, but a psychological one, if you will, and the goal of treatment is to relieve the stress, relieve the burden, increase exercise capacity and stamina, all things that can be measured in clinical trials as we have done over the course of many years.
Dr. Moira Gunn:Is this the thickening of the heart muscle, or is that different?
Robert Blum:That's right, it is a thickening. So hypertrophic cardiomyopathy is a disease that has a hereditary or genetic linkage. There's a familial link to this disease, and patients who have hypertrophic cardiomyopathy can develop an obstruction in their heart, which creates a high pressure gradient, and that's because there is a thickening of the heart muscle because it's in a constant hyperactive state. So one has a goal with a potential new medicine to inhibit the contractility, to relax that muscle, to lessen the thickening, relieve the pressure gradient, and be enabling of these patients to live more active functional lives.
Dr. Moira Gunn:I think it's a little difficult to separate out some of the earlier or driving conditions from the the overall heart condition. I mean, many people say, oh, I have high blood pressure. Well, I'm afraid I'm get I'm approaching high blood pressure. I'm taking pills for it. That ends up creating a heart failure condition or a heart condition, or is it which one's the chicken and which one's the egg?
Robert Blum:Well, that's the interesting thing is it's a difficult thing because there's a circular feedback system here that patients oftentimes will have comorbidities. They may have high blood pressure, they may have problems with the electrical rhythms of their heart. All these things combine together, oftentimes with other syndromes such as diabetes or metabolic disease, putting more and more pressure on the heart. So patients with heart failure oftentimes have complications associated with other concomitant conditions. What we unfortunately don't have in our armamentarium of medicines are a lot of drugs that work directly on the mechanical function of the heart, and that's where Cytokinetics comes in.
Robert Blum:Over twenty five years of research has led us to a place where we're developing potential new medicines that act directly on the machinery of the heart to either enhance or suppress its function as would be beneficial to patients. So as a result of that, we've developed a pipeline of medicines that we're developing in different stages of clinical trials. We hope to have multiple new medicines for those cardiologists who treat conditions underlying heart function?
Dr. Moira Gunn:Well I have to say as I study your clinical trials, you begin to see the fine points of your heart. For example, in one case, have a weakening of the heart, and so you have a muscle activator. In another case, it's hyperactive. So your heart's acting differently, and the hyperactive one then needs an inhibitor. Take us through this.
Dr. Moira Gunn:It's almost like the same drug or the same idea for a drug.
Robert Blum:We've developed three potential medicines all directed to the same protein, the same enzyme called cardiac myosin that is driving the force production of heart cells. So one of these is an activator, two of them are inhibitors, and we can develop all three of them for different conditions that relate to heart muscle mechanics. And in that way bring forward a potential pipeline or portfolio of new medicines for cardiologists that treat these underlying conditions.
Dr. Moira Gunn:Now, one of your phase three trials is in the pediatric space. Are heart conditions common in the pediatric space, and is it different other than the age of the patient?
Robert Blum:Unfortunately it is common, and initially we studied adults with this condition of hypertrophic cardiomyopathy, but it is a genetic predisposition, and it can emerge in adolescents or children. So now that we've seen evidence to support the use of our cardiac myosin inhibitor in adults, it's now incumbent upon us to evaluate its potential in adolescents, and ultimately in pediatrics, because ultimately we hope all of these patients may benefit from this innovation.
Dr. Moira Gunn:Now in phase one, that's the first when you go into humans, you have what's called a fast skeletal muscle tropopin activator. I may not have that pronounced correctly. What is skeletal muscle, and what has that got to do with the heart?
Robert Blum:So very interesting, you should ask that. So you have cardiac muscle, you have skeletal muscle, you have smooth muscle, and your various muscle types have evolved alternative forms of these same proteins that drive muscle contractility outside of the heart as well. So we're developing an activator of fast twitch skeletal troponin, which is a regulator of skeletal muscle contractility. And here we've seen evidence that activating skeletal troponin can produce more skeletal muscle force and power, and also alter time to muscle fatigue. So these are not your cardiac drugs, these are potential new medicines for diseases of neuromuscular pathophysiology.
Dr. Moira Gunn:So you started with the heart, but that's just where you started.
Robert Blum:We started with the heart. We're extending this know how or these innovations to skeletal muscle, and quite frankly, this illuminates for us what we believe to be a pathway to healthy aging over time. Our aging demographics call for potential new medicines that can be enabling of us to live more active and more functional lives. So how we approach active daily living is rooted, we believe, in muscle biology and cytokines hopes to be both a pioneer and a leader in areas of healthy aging over time as well.
Dr. Moira Gunn:Now I want to return to the current clinical trials because you are enrolling in a number of them and all over the world, mostly in The United States, but all over the world. And what is it like to be generally in one of these clinical trials?
Robert Blum:There are a number of visits, a number of assessments that get performed, and patients are asked to participate actively in measures of muscle function and also quality of life over the longitudinal period of their study, and our goal with these clinical trials is to conduct an experiment. Does the addition of one of our experimental medicines, when added to standard of care, provide even more therapeutic gain.
Dr. Moira Gunn:I keep coming back to December. It may be thumbs up, thumbs down. I keep thinking about this. It's twenty seven years to be an overnight success.
Robert Blum:It's funny you should say that.
Dr. Moira Gunn:Must be pretty daunting.
Robert Blum:We oftentimes joke that nobody will ever accuse us of being an overnight success. I started this company twenty seven years ago with leading academic scientists, and we industrialized the work that was occurring in their academic labs at Stanford and UCSF and UCSD, and it's taken us this many years to do all of the pioneering work that we've done, both in our laboratories and in clinical studies around the world, and it may come to a focal point, transformative as we hope it can be, in December. This is a very exciting time. We're a larger company now. We have a footprint all over the world, but we're still a company rooted in science.
Robert Blum:Science is in our soul, and we do believe that our patient centricity has been the guiding light for us all of these many years. So being on the cusp of potentially enabling of one of our medicines to be in the hands of physicians and patients, it's an incredibly gratifying and fulfilling thing to think about.
Dr. Moira Gunn:Well, we're pulling for you here at Biotech Nation.
Robert Blum:Thank you.
Dr. Moira Gunn:Thank you.
Robert Blum:Thank you very much.
Dr. Moira Gunn:Thank you for coming in. Please come back, give us an update.
Robert Blum:I look forward to that and hopefully the next time we have an opportunity to speak we can be talking about FDA approval for one of our medicines. I should also mention, we're seeking approval all over the world, in China, also throughout Europe. Our goal is to ensure that our medicines are available with equitable access regardless of geographic borders.
Dr. Moira Gunn:Robert Blum is the CEO of Cytokinetics. More information is available on the web at cytokinetics.com. That's cyto,kinetics,cytokinetics.com.
