Greg Renza (00:11):
Hello, and welcome to another addition of Pathfinders. The podcast series from RBC Capital Markets that explores the fast moving world and biotech and pharma. I'm Greg Renza, Senior Biotechnology Analyst here at RBC. I'm here today with Dr. Ted Love, president and CEO of Global Blood Therapeutics. It's a pleasure to have Ted who joined GBT in 2014 to lead discovery, development and commercialization of therapeutics and blood-based disorders with a focus on sickle cell disease. Dr. Love's travels span a multitude of organizations and clinical training. Dr. Love has been a staunch champion of meeting the medical needs of underserved populations throughout his career.
Greg Renza (00:53):
Global Blood Therapeutics is at a pivotal juncture in the company's growth trajectory, having brought its first treatment for sickle cell disease to market. In this episode of Pathfinders, we're looking forward to getting Dr. Love's perspectives on leadership within biotechnology, guiding others amidst the extraordinary rate of change and innovation within the sector, but also managing through adversity and overcoming uncertainty.
Greg Renza (01:21):
The COVID-19 pandemic is a real time case study, which amplifies his steady hand, focus on the end goal and operating what is a mission driven organization. Ultimately, we see Ted's approach infused by the theme of empathic leadership. It is Ted's ability to lead with empathy in our view, that is a thread throughout his career and the vision and execution at GBT to inspire others, get results and realize the potential for therapeutics amongst the underserved population. We look forward to learning about GBT past and present, and also what is on the horizon for next generation treatments. Ted, thank you so much for joining us today.
Dr. Ted Love (02:00):
Thank you Greg for that very kind introduction. It is a pleasure to be here.
Greg Renza (02:04):
And there's always an origin story, yours is no exception. So what has made you passionate about a career in biotechnology?
Dr. Ted Love (02:12):
Well, I started out, actually Greg, with an interest in medicine mainly because I was pretty good in science and math as a kid, and that led me down a career in medicine, initially with the idea I'd go back to Alabama and practice care in the community that I grew up in. When I was at Yale, I began to be influenced that I should think about an academic career that continued when I was at Mass General. But I was recruited by Genentech and thought that represented a really nice opportunity to leverage my background in science and medicine in a way that might produce innovative therapies. And that was a very good decision for me, even in retrospect.
Greg Renza (02:54):
At the time of GBT in its early days, certainly at a time where I am sure you had a choice in where you could allocate your time and resources, what motivated you to join GBT to actually establish that leadership role in order to take GBT as an early company to the next level?
Dr. Ted Love (03:16):
Well, one of the things I also remember well from my clinical training at Yale, and then later at the Mass General is that sickle cell patients were very sad, indeed. It was a sad situation because the patients were typically young because sickle cell disease, unfortunately, for which you typically die for early young, our patients were almost always African American and they were often poor. And the healthcare system, quite frankly, had not a lot of great therapy to offer them, and there was really a lack of enthusiasm to treat those patients. And I later learned there was really a lack of enthusiasm to invest in solutions to solve their problems. So when GBT came along to me, it really reminded me of all the things that I had not done, and quite frankly, nobody had been doing for these patients and I saw it really as a call to action for me personally. I was retired at the time, so it really meant I had to go back to my family and raise the issue of whether or not me taking another full-time job would fit with them. And they actually ended up seeing it exactly the way I just described, and they felt that it would be really ideal for me to end my career by coming back and doing a stint to focus on helping sickle cell patients.
Greg Renza (04:45):
That's fantastic Ted. And that just reminds me of what underlies our discussion today is the concept and the essence of GBT being what is a mission driven organization. And with that, a common theme that we see and how you manage others' drive for progress and continue to innovate with GBT is the ability for you to lead with empathy, the concept of empathic leadership. I'm curious if you could comment a bit on what that means to you, but also reflect that on the end patients in mind, the end families in mind to enable you to inspire others within your organization.
Dr. Ted Love (05:25):
I think empathy is a very powerful emotion. When I cared for patients. I really did try to imagine that the patient I was caring for might have been my father, might have been my brother, might have been my sister or mother. And that did inform looking at these patients in a very different way than you might, if you didn't really think of them as being part of your family. And I think that's a very high standard, by the way, I'm not sure if every physician sets that standard, but I think if you do it really is a great guiding light. Because, really what you're doing for that person is you're doing what you would want done for you if the tables were turned.
Greg Renza (06:15):
Let's turn to Oxbryta. Oxbryta is GBT's first sickle cell treatment. Maybe give us some color on how it works and what impact it does have on patients and their families.
Dr. Ted Love (06:25):
So maybe we'll just step back to a very high level and talk a little bit about what is sickle cell disease. Sickle cell disease, it's a rare, about 100,000 patients in total in the US. It is a genetic disorder. So people get sickle cell disease not from anything they do, but from the genes that were passed on to them by their parents. The reason the disease is primarily associated in African Americans in the United States is because it was largely brought into the United States through importation of slaves from Sub-Sahara Africa. And the reason it was endemic in Sub-Sahara Africa is that while the disease is a terrible thing to get, the trait, which is not the disease, but the trait does one copy of the bad gene actually protects you from malaria. So in areas of the world where malaria was highly prevalent, this advantage of having one bad hemoglobin gene, one sickle hemoglobin gene, actually was a survival advantage. So that passes on in higher numbers. The problem is when two individuals with sickle trait have children, one out of four of their children, statistically, will get two bad genes, and that is the devastating condition known as sickle cell disease.
Dr. Ted Love (07:53):
So what is sickle cell disease? Well, it's a single mutation of literally one amino acid on the hemoglobin molecule. And the reason it is so devastating is that that mutation changes the charge on the hemoglobin. And by changing the charge on the hemoglobin, you make hemoglobin interact with other hemoglobin molecules because all hemoglobin molecules have the opposite charge on them. So basically you're imagining a magnet where initially there was not the opposite charge on a magnet, so they wouldn't stick together, and suddenly you inserted that opposite the charge and now the magnets began to stick to each other.
Dr. Ted Love (08:43):
So what GBT was founded on was the idea of, could we make a small molecule, which could be formulated as a simple daily tablet that would bind to the hemoglobin and stop the hemoglobin from sticking together, because that is actually the molecular basis of the disease. And what we found very early on is that in very simple test tube studies, we could make molecules that would very effectively stop the hemoglobin from sticking together. We advanced on into animal studies where in mice that we genetically modify to have sickle cell disease, we could quickly rapidly begin to reverse the phenotype of sickle cell in those animals. And as you know Greg, when we went into humans we replicated the same phenomena, we showed that we could very quickly begin to make sickle cell patients take on more of a phenotype moving towards sickle cell trait, where their hemoglobin goes up, their sickle cells are going away. We think their organ survival and their life survival will be improved, but it takes time to show that. But that is the pathway that we committed to and that's the pathway that we're still very much on.
Greg Renza (10:06):
And it's amazing, Ted, how you tie the biology, but also the history to converge on what your mission is at GBT. And I'm curious, how do you scale that to a point where that view, that focus, is ingrained in your company's DNA? Especially in a field and in a sector where there is considerable reliance on third parties, on external stakeholders and a challenge for you to maintain, I think, unity and rigor and determination within a single organization to get a drug like Oxbryta from essentially a test tube into patient's hands.
Dr. Ted Love (10:52):
Well, I mean, we're very intentional about all of this Greg. Number one, we talk to ourselves about our mission and our commitment to deliver on our mission. We also, with a high degree of frequency, invite patients and caregivers into the company to meet with all of our employees, to talk about their experience with sickle cell disease and even their experience using Oxbryta and how it has led to changes for them personally or for their patients if they're healthcare providers. We also make sure that when we're recruiting people, we're recruiting people that are committed to the mission of a company. So it's a full effort. We keep our mission front and center in everything that we do.
Greg Renza (11:41):
You launched Oxbryta in the face of the COVID-19 pandemic, that's quite a great deal of adversity to encounter. What challenges did you face along that journey either due to the pandemic itself or things that were exacerbated by the pandemic?
Dr. Ted Love (11:57):
Yes, Greg, you're absolutely right. And just to remind everyone, Oxbryta was approved in November of 2019. So COVID really had not hit the US, there may have been some cases in the US, but we were essentially unaware of it. So GBT did have almost one full quarter of a launch that was un-impacted by COVID, and actually it was an extraordinary launch. We probably were on track to enroll approaching 2000 patients, but in the last two weeks of the quarter the pandemic was declared and patients literally stopped going to see their doctor, and of course enrollments plummeted. Since then patients have continued to be reluctant to see their doctor. We have supplemented with telemedicine and phone calls, but that has not been able to return the enrollments back to where they were before the pandemic started. So we've been essentially capped and we've even had situations this year where sickle cell doctors have literally been diverted from the care of sickle cell patients to care for the terrible scourge of COVID cases that they were having in their hospitals and in their ICU. So it's been highly disruptive, but we're very optimistic about the long term.
Greg Renza (13:23):
And COVID-19 has given everyone a glimpse of how difficult it can be to deliver a treatment in such an environment, to execute on R and D and also bring medicine this to patients. So how do you ensure that a company like GBT is resilient through these tough times?
Dr. Ted Love (13:41):
Well, I think it does involve a lot of focusing on the mission. If you are committed to a mission, you're very reluctant to give up on that mission. And in fact, when you encounter adversity, rather feeling sorry for yourself, what you do is you focus on how am I going to deliver on the mission despite what's going on. And that's exactly what we've done at GBT, we don't ignore the pandemic, we can't ignore it, but we do focus more on our mission than anything else. And so that actually guided us during the pandemic to say, no, we are going to quickly take our sales force, our field force out of interacting with healthcare providers. We don't want our people to be a basis of making a healthcare professional sick, or making a patient sick. So our first step really was to protect patients, protect healthcare providers, and of course protect our employees. That may not sound like it's focused on your mission, but if you think about the big picture, that was very much a mission driven decision.
Dr. Ted Love (14:54):
But the next decision is to figure out, well, how do we still communicate? We need to communicate. So we quickly began to equip all of our people in the field with the technology and the tools to begin to communicate using other methods and other materials that didn't involve some of the things that we were prohibited from during the pandemic. So we've continued to look at the challenges presented by COVID and to quickly figure out how we're going to meet those challenges.
Greg Renza (15:26):
It has certainly been an unsettling and just unprecedented of time with the pandemic. And in biotechnology and in therapeutics, we are always chasing our ability to know the end market, to size the peak opportunity. But at GBT how do you and your colleagues approach this in a way that it's not just sizing markets, but it's actually knowing and understanding them, knowing the patients, the families, and the constituents that support them?
Dr. Ted Love (15:56):
Well, I mean, I think we could talk about it in marketing terms, but we could also talk about it in human terms. The vast majority of people with sickle cell disease are dead before their 50th birthday. I believe the average survival for a male is about 42, and it's about 45, I believe, for a female in the United States. These are very sobering numbers and they're not improving, so if we're going to improve those numbers we're going to have to do something to get in front of the pathology that these patients are aggregating over the first 40 years of life to really give them very little life beyond that 40th birthday. So we really feel that is going to be important for as many patients who can possibly benefit from Oxbryta get access to it.
Dr. Ted Love (16:52):
Our label, is actually, covers essentially 100% of patients with sickle cell disease. The label simply says, you have to have a diagnosis of sickle cell disease, and you have to be above age 12. And we're working very hard to reduce that age requirement ultimately down to six months, which is roughly the age where sickle cell begins to affect you. The first six months of life, you're really protected by the fetal hemoglobin that you're born with. But after about six months people begin to manifest complications of sickle cell disease. And our goal is to make the drug available to 100% of them. If I only a third of the patients gained access to Oxbryta we would be doing a tremendous benefit for those patients and from a marketing perspective, obviously it would be a very successful drug. But I like to think about it from the perspective of what proportion of these patients can we help.
Greg Renza (17:56):
We know that you've been working on next generation therapies and even treatments that could rival the potential of one and done genetic therapies. Curious Ted, if you comment on what your hopes are for drugs and options beyond Oxbryta and how we would think about functional cure potential.
Dr. Ted Love (18:17):
Well, I think there's an analogy here with the disease like HIV, where when I was in medical school in New Haven, we started to have these patients come in with what we later have named HIV or human immunodeficiency virus. We treated those patients for their complications, we couldn't treat the virus. We didn't have any drugs that treated the HIV virus itself. So we used to treat the opportunistic infections that they got. That's largely been the way we've approached sickle cell disease. We've really been downstream treating the consequences of the disease. And as analogous to HIV, treating the complications was of benefit, there's no doubt there was some benefit, but the big breakthrough in HIV came when we actually got all the way back to treating the virus, which was causing the proximate problems that led to the downstream complications that we were treating. So by analogy, the HIV virus equivalent in sickle cell disease in my belief is polymerization of the hemoglobin, that is what the mutation causes. And so we are focused on stopping that as our number one cause, and that's what Oxbryta is approved to do.
Dr. Ted Love (19:52):
One of the things we do know about Oxbryta is that even with a gram and a half per day, we're not able to block enough of the polymerization to be curative. And so we focus on other efforts to see if we could invent other molecules which could get to those levels of sickle hemoglobin polymerization inhibition. And we think we're there, we hope we're there with this molecule called 601. But we also recognize that there are patients who have pain already and there probably always will be. And we're also developing a p-selectin inhibitor called inclacumab that is directed at the downstream complication of pain crises through its anti-inflammatory activity.
Dr. Ted Love (20:45):
So we want to be a company that is known as the sickle cell company. We want to offer a range of products to help these patients. And our ultimate goal is to make this a well managed chronic condition for which patients do not die prematurely.
Greg Renza (21:04):
That's very helpful and inspiring. And on the human capital side Ted, building an organization that reflects inclusivity and diversity is key to the empathy equation. And at GBT what experiences help you to embody that inclusivity and diversity?
Dr. Ted Love (21:24):
We, every year, look very carefully at how we're hiring, how we're promoting, how we're compensating. We look at it by gender. We look at it by race. We look at it by sexual orientation. We really are very serious about making sure that there is no bias in our company. And I think the only way you're going to be sure that you're doing a good job of that is to be very aggressive about looking for it. Because, we always talk about unintentional bias, well, if you look carefully you can see it. And if you see it, you can then try to do something about it. So we look for bias in our company, even though we're a company that really wants to make sure we have no bias, we assume that one day we could and we'd like to diagnose it and treat it as quickly as we could.
Greg Renza (22:15):
When you think about the future of medicine, what are you envisioning, certainly, as therapies become more targeted, more impactful and ideally are available to those who need them? What do you see as the future?
Dr. Ted Love (22:33):
Well, I think we've got a bright future ahead of us. We have done tremendous work at finding powerfully innovative solutions toward terrible problems. And the COVID pandemic that we were just talking about is such an amazing example. We are talking about a disease that didn't exist a couple years ago, and it quickly spread around the world and began to kill us very rapidly. We develop antibody solutions, vaccine solutions and now small molecule solutions that are highly effective against this therapy already. So I think what we're seeing is not only the accumulation of highly effective therapies like Oxbryta, like Herceptin, other drugs that I've worked on in my past, those drugs are going to become increasingly cheaper as we go forward and they've lost protection, and they'll be more widely available, hopefully, all around the world. But we've also seen an industry which can pivot even more quickly and react to things.
Greg Renza (23:48):
That's a fantastic case study where during the blight of a pandemic, there was a call to action and the practitioners, care providers, developers, and even the bio tech sector responded to such a call to action. Truly, a unifying event to overcome what was quite a challenging time.
Greg Renza (24:10):
Maybe in closing, Ted, as well as your interest in helping underserved medical populations, I know that you and GBT have established ways to give back to the community in more ways than just providing Oxbryta, especially with your foundation. Tell us about that.
Dr. Ted Love (24:30):
Yeah. I suspect Greg, that we are the first company ever of this age and size to actually create a foundation, but it's completely compatible with who GBT is and who we're trying to serve. We are trying to be fundamentally philanthropic and mission driven and patient driven in our core. And we, again, want to make sure that we're delivering on that promise with the therapies that we discover, develop and commercialize and or give away. But we also recognize that some communities need financial assistance, they need people to show up and volunteer, they need mentors for their children or the people in their community.
Dr. Ted Love (25:20):
So GBT has committed to all of the above and our foundation is something I'm very proud of, but it's simply one thing that we've done. We've also committed to funding a therapeutics conference every year that's focused on how do we actually innovate and change the care of sickle cell disease. I joined with a group of other leaders here in the Bay Area, and we created Life Science Cares. This year we're probably going to raise over 2 million and give away that to charitable groups in the Bay Area that are doing work to help the most disadvantaged and the most underserved. And we're also showing up to donate, to help with vaccination, help with food insecurity. So we've really tried to show up in every possible way to show people that we are truly concerned with making the world a much better place.
Greg Renza (26:17):
That's fantastic Ted. I think that's a great place to close. Dr. Love, I want to thank you for all of your insights into the biopharma sector today, your story, your vision and execution of GBT and the concept of leading with empathy.
Dr. Ted Love (26:35):
Thank you, Greg.
Greg Renza (26:36):
What else can we expect from our fast moving industry as we start to close out the year and look beyond to next, we'll be keeping track right here on Pathfinders. Until our next episode, I thank you all for joining us. If there are any areas that we've covered today where you'd like more information, please don't hesitate to contact us directly for a more in-depth discussion, or visit our website at RBCCM.com/biopharma. This is Greg Renza thanking you and signing off for now.
Speaker 3 (27:10):
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