Diego Rey, Co-founder and Chief Scientific Officer at Endpoint Health

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Saul Marquez:
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Saul Marquez:
Welcome back to the Outcomes Rocket, Saul Marquez here today, I have the privilege of hosting Diego Rey. He is a co-founder and Chief Scientific Officer at Endpoint Health, a company on a mission to bring lifesaving targeted therapies to critically ill patients. Diego previously co-founded GeneWEAVE acquired by Roche, a company that develops diagnostics for guiding antimicrobial therapy. He also serves as an expert Part-Time partner at Y Combinator. Today, we’re going to dive into the work that they’re doing at Endpoint Health and how it’s making a difference in health care today in one of the most challenging times in our current environment. So, Diego, such a privilege to have you here, and certainly looking forward to our conversation today.

Diego Rey:
Thank you. Really happy to be here.

Saul Marquez:
Yeah. So Diego, before we dive into Endpoint, I mean, you have a very interesting background and history in health care, so I’d love to park there for a second and find out more about that. And also, what inspires your work in health care?

Diego Rey:
Sure, yeah. So I actually started off studying electrical engineering as an undergrad at UC Santa Barbara. And at the time, it kind of led me from there to health care. A bit of an odd story, I guess, or not subprocess, which is in electrical engineering. I felt that I was maybe several steps removed from an end-user. That’s what was going through my head. I felt that I would be working on a subcomponent of a subcomponent of a system that may or may not directly interface or impact an end-user. And I had this desire to get closer to being able to directly impact an end-user in something that I would build or contribute to. At the time, I was also really interested in the life sciences because of the interdisciplinary nature of the problems and solutions in this space coming from an engineering point of view. So if I took this kind of desire to directly impact an end user to an extreme, I thought that one way of doing so was to study medicine and become an M.D. because then there’s nothing really in between you and an end-user. They’re your patients. And so at the same time, again, though, I realized that I was too much of an engineer and I really just wanted to build things. So in the end, what I thought was a bit of a compromise was where I landed, which was to study biomedical engineering, which I did at Cornell University for my Ph.D. So that’s what kind of led me down this path, the very beginning coming from engineering. But more specifically, what really inspires and motivates me in my work in health care is the ability to develop products that are enabled by new technologies than to directly improve the lives of the patients.

Saul Marquez:
Wow, that’s cool, man. And, you know, really interesting that you took that route. You know, I mean, I just look at the world today, Diego, and it is literally like shaped by STEM, you know, I mean, whether it be your provider or an engineer, I mean, it’s being shaped by it, period, right?

Diego Rey:
Yeah, exactly.

Saul Marquez:
Yeah. So the route you took hey, it’s great. You know, by the way, my wife’s a biomedical engineer too.

Diego Rey:
That’s smart.

Saul Marquez:
I always say she’s a smart one in the family. And so, Diego, you know, and you got your Ph.D. in it. Obviously, you’re committed to this and you had some success with GeneWEAVE and your exit to Roche. Talk to us about what you’re doing today with End Point Health. How are you guys adding value to the health care ecosystem?

Diego Rey:
Yeah, definitely. So we started EndPoint in twenty eighteen and we were really on a mission to improve the outcomes of critically ill patients specifically. And one of the areas of focus for us is sepsis, which is one of the biggest problems in critical care. And sepsis, what it’s a life-threatening immune response to an infection. And today you actually hear about it coincidentally, a lot more on the news than ever before, because it turns out that folks who die with COVID-19 do so typically due to sepsis in most cases. But even prior to the pandemic, it already had a huge burden in health care, with an estimated cost about 60 billion in the US. And it’s linked to actually globally to more deaths than cancer each year. And again, this even before COVID-19 Right. Yeah. And so despite this, there’s actually no FDA approved therapies for sepsis. If you can imagine. The only therapies that are currently in routine practice today for sepsis are supportive care, things like ventilation, and fluids. And so this really makes sepsis one of the largest unmet clinical needs that’s out there. And so the lack of available therapies. So it’s not. Because of a lack of trying, there have been hundreds of past clinical trials in sepsis. Unfortunately, though, they’ve all these trials in the past have been neutral or negative, and they just failed to demonstrate an improvement in outcomes in these patients. And so our underlying hypothesis, at Endpoint is important for why this has worked in the past and for how to move forward from here is that sepsis is not a single disease. It’s actually a syndrome. It’s not something that can be treated in a straightforward manner. It’s a description of symptoms and that is very heterogeneous in nature. And so meaning that any given episode of sepsis can be different from another. And so what we’re aiming to do at Endpoint health is to develop the means of defining and then also identifying each of the underlying biologically defined conditions that make up critical syndromes like sepsis and that are each individually treatable. So, for example, if you take a subset, patients make an exhibit immunosuppression or hyper inflammation or have coagulation disorders. And as you can imagine, each of these underlying conditions require very specific and different treatments. And not all sepsis patients may exhibit all of these conditions when they’re exhibiting sepsis. So the tools that we develop at the end of the day, they’re companion diagnostics. They’re the tools that we use in clinical trials and then later in clinical practice to identify patients exhibiting these specific conditions and to target the appropriate therapies to those patients. And so in doing so, we hope to accomplish what will really be some of the first positive trials and critical syndromes like sepsis. And the endpoint in these trials are mortality for which we hope to dramatically improve and dramatically drop if successful. So if successful, what this would mean is that we have a tremendous positive impact, not only in improving patient outcomes, but also in lowering hospital costs and lowering costs of the overall health care system.

Saul Marquez:
Yeah, that’s really interesting. And, you know, it’s shifting the paradigm on things like sepsis, Right. It’s not that that’s the disease. It’s a syndrome. And you guys are breaking it apart, giving us a better understanding of each component that leads to it. So as you focus the work to tackle some of these underlying components, what would you say you’re doing differently or better than what’s currently available?

Diego Rey:
Yeah, so although we’re doing something that’s new, as the company clinicians have really and researchers have really known for a long time that sepsis is a heterogeneous syndrome that requires stratification in order to have a shot at successful therapeutic development. And the problem is that the ability to capture the data necessary to analyze it in order to do this sort of stratification and not just in a research setting, but in real-time, in order to be able to translate this research into clinical practice, it was just not possible until fairly recently. So to do so, we’ve developed two platforms at Endpoint. One is a software system that captures digital data from the electronic health record and runs machine learning models using this data on the cloud. And what these models do is identify biologically defined subgroups in the first use in acute respiratory distress syndrome patients.

Diego Rey:
Another condition that is very common in COVID-19 and these subgroups are predictive of therapeutic response. So we’re now working to deploy the system as a software, as a medical device, post-marketing authorization by the FDA. the second platform we’ve developed is an in vitro diagnostic blood test that measures expression levels of specific MRN molecules from critically ill patients from a blood sample. And we use this to identify subtypes of sepsis patients and based on their immune response. And so these subtypes likewise are also predictive of differential therapeutic response. So at the end of the day, we have a software tool and in vitro diagnostic tool, each which can be used as companion diagnostics. And finally, our business model is actually to then in license or code, develop clinical-stage therapies, and then use these tools to enable the appropriate trials that target the therapies in these trials. And the reason for this model is that we’ve actually identified many previously already developed therapies, many of which actually were previously attempted in sepsis that we think have a high likelihood of success in sepsis, but when actually targeted to the right patients. So back to your question. This is in contrast, I think, to many companies that discover new therapies, which is also critically important. But instead of doing that, we’re usually what companies discover, new therapies, they partner or sell the pharma to then develop the therapies, In our case, we’re developing the therapy ourselves and later-stage clinical trials. And the other thing that’s unique about this is that few companies are built from the ground up with integrated software, in vitro diagnostics, and therapeutics all under one roof and really built to work together from the get-go. So on top of all this, with this integrated solution, what we then have the ability to do is capture data also from existing care and link it back to outcomes.

Diego Rey:
And so this enables us to not only develop new therapies but also to optimize existing care. So kind of bringing it all together. Rather than precision medicine We call this precision care. We consider it actually a new category of medicine where we’re not developing therapy and then applying it to multiple indications, which I would consider more of a traditional precision medicine approach when those therapies are targeted. But instead, we’re focused on optimizing all of the care for a given indication. And the reason we started Endpoint Health is because we felt that to really improve outcomes and critical care in the space, that this is a sort of approach that was really needed. And companies like the one we’re building really just did not yet exist.

Saul Marquez:
That is really interesting, Diego, and very different. On the one hand, you’re a software as a medical device and on the other hand, you’re offering in-vitro diagnostics. But on the sort of back end of it all, you’re enabling bringing therapies to market that are effective. So it’s a pretty complex business with a lot of promise. And I’m thinking about just the opportunities that exist and the various stakeholders that could get involved. Who are you guys looking to partner with? And you know, who’s going to be using your technology? And I asked that just to engage the listeners today on potentially how they could work with you guys.

Diego Rey:
Yeah, definitely. So we’re very much partner-oriented and driven by that, because like you said, we’re covering a lot of ground. So one of our key partners, of course, is the clinical research community. And what’s been really interesting and something that we didn’t experience in the past and another geneWEAVE and even that Roche is the amount of engagement and interest and real excitement around what we’re doing because it’s such a huge need Right. just there hasn’t been much activity in the space. So the amount of enthusiasm and bind that we’ve been getting from the clinical research community has been really exciting. And so we partner with clinical researchers because that’s where we conduct our trials, of course. And in some cases, we’re translating research that was developed by collaborators into the clinic. In other cases, we develop our own solutions. And at the end of the day, the folks who will use our products are the clinicians. So the workflow is essentially, patients would be admitted into the emergency department or ICU, gonna get a blood sample drawn data might be pulled from electronic health records. And in the background, we’re running our algorithms based on the blood test results or on the HRR variables that we collect. And depending on how patients are progressing in the worst cases, that the sepsis patients progressing to shock and refractory shock, for example, which is where they don’t respond to this oppressor’s, then our results are then used prior to making treatment decisions. And ultimately, hopefully when a new therapy becomes available and we’re successful in our clinical trials for novel therapies, that the test would enable treating specific patients, using our test for the particular therapy. The other partner, of course, is major partners, pharma companies and biotechs. So I mentioned that we’re not developing our own new molecules from scratch. We’re looking to in-license or code develop therapies that biotech and pharma companies have previously developed and our manufacturing.

Saul Marquez:
Yeah. And, you know, and you mentioned there’s not a solution to sepsis. For example, one thing that we’re dealing with here or discussing, there’s not a solution, not because of lack of trying, but just things haven’t worked. So is there a bunch of stuff on the shelf that didn’t work that you guys are looking to say, hey, you know, we have a new way to get there?

Diego Rey:
Yeah, exactly. That’s exactly it. So in some cases, it’s not necessarily on the shelf therapies that are being used in different indications. In other cases, they are on the shelf. So it’s kind of anywhere in between. But both of those scenarios are currently exist.Yeah,

Saul Marquez:
Got it. Fantastic. Thanks for clarifying that. So you know, the question about improving outcomes and making business better, you know, that’s something that we’re focused here on the podcast. Diego, how are you guys doing that today? And obviously, you guys are two years into this, so maybe you have some examples or if not, then maybe how you plan on making a big difference here.

Diego Rey:
Yeah, as you mentioned, we’re two years in approaching two years and. So we’re really just getting started, so our products are not yet commercialized, are not FDA authorized on the market, so we have yet to demonstrate improved outcomes by the use of our products in the clinic. But in the meantime, it was really motivating our work that we have demonstrated the potential for improving outcomes in both sepsis and acute respiratory distress syndrome. And we’ve done so initially through observational studies and retrospective analysis of past randomised control trials and the results of this work. And, of course, need to be further validated in our own prospective randomized controlled trials. But the index that’s the subject of our next phase of our company. But in the meantime, if we’re able to replicate the sorts of results that we’ve seen so far in the past analysis, we believe that the commercialization of our products will result ultimately in tens of thousands of lives saved each year in the US alone. And that’s again because ther are therevery few treatment options for these patients. And so some of our therapies and more broadly interventions will be the first in these patient populations that are commercially available.

Saul Marquez:
Yeah, because right now, I mean, you get sepsis, you’re probably going to die, you know, and it just happens too often that what you guys are doing today is kind of laying the groundwork for how we’re going to improve this area, right?

Diego Rey:
Yeah, exactly. It’s you know, we feel that not only are novel therapies needed but even with existing care, which is mentioned before, ventilator settings, fluid management, steroids, for example, we hear a lot about covid-19 these days. One of the few things with a positive signal, all those things could be managed better thinking. And even if it’s not a novel therapy have the potential for dramatically improving outcomes. If a targeted, optimized, but ultimately by targeting to specific patients who would respond, in some cases avoiding therapies and in cases where patients may have an adverse response, that’s also just as crucial. And it’s something we also aim to do as a company.

Saul Marquez:
Yeah, and Diego, I love your idea of precision care care.. We talk a lot about precision medicine, getting one thing right and then applying it broadly. But you’re talking about precision care here. So you’re OK with that. Let’s dive into that because I really like this idea.

Diego Rey:
Sure. Yeah, definitely. I think maybe that last example I gave is a good kind of case point for this, which is we’ve seen, in fact, in some cases where a dramatic improvement in outcomes can be achieved by avoiding a particular therapy in a specific set of patients. So that’s really kind of the opposite of a traditional pharma business model where we’re not we’re not selling any therapeutic Right. this is just a companion diagnostic that flaggers, which patients should not receive a particular dose of a specific therapy. But looking at this from the concept of precision care, though, this makes just as much sense as enabling a new therapy that would improve an outcome. And the reason is that at the end of the day, it’s not about selling the therapy or even selling the diagnostic, it’s about improving outcomes. And so we’ve set up our company in a way to really thrive if and when the world transitions into what would ultimately be more of a outcomes-based way of practicing medicine from a business side of things. So when basically when you get paid as a company, when outcomes are improved. And so that’s sort of a scenario we again care just as much about avoiding a therapeutic intervention as we do, enabling a new therapeutic intervention because we’re linking everything back to just improving outcomes.

Saul Marquez:
I love it. That’s so awesome. And as you think about the two years, I mean, I’m sure it’s been winding roads and just that challenging to get it to where you guys are today. If you had to point to one particular setback or experience that you believe has made you guys better, what is that? And was the key learning that came out of it?

Diego Rey:
Yeah. So an example of a specific big setback was actually back at my previous company. And first, a little background on what we did. So we created a new technology that enabled the detection and identification of live bacteria and the ability to determine the response of the organism to an antimicrobial agent and doing this all in a matter of hours directly from a patient’s specimen. So this was actually a big deal at the time because prior to our approach, the only way to really do this in a clinical setting was using traditional clinical microbiological tools and techniques that required growing the organism to isolate it. And typically that took an overnight step and then testing it for its response, an antibiotic susceptibility to an antibiotic which required growing the organism again. So instead, we were able to do all of this with our technology. Directly from a specimen without growing the organism in a matter of hours, our first product was a diagnostic for detecting methicillin resistant staph aureus, or MRSA. And after years of work, we realized that our original approach, which included the detection of specific genes, in this case, the aging in MRSA, it was just not working well enough to enable the diagnostic performance that we really needed for our product. And this is despite the fact that this initial approach from the basis of our entire company and the core of our intellectual property.

Diego Rey:
So at the same time, though, along the way we developed a proof of principle for the ability to detect MRSA, not by detecting the gene, but instead by directly measuring the response of staph aureus to the antibiotic. So we had a potential solution. But as you can imagine, we needed to, in effect, recreate the entire company moving forward, including convincing our board of directors that this was the way forward. So really, really challenging time, of course. And in the end, the lesson was that was one. But we thought we actually already knew, which was one of customer development, which we almost had Right. we didn’t actually pivot in the product we were making. We pivoted instead in how we got there. And so what we initially failed to see was that what the market really needed was not something that was just suitable for MRSA test, but was more broadly the ability to do susceptibility in a better way. And ultimately this opened the door for a much larger opportunity. So our customers dealing with infection control in hospitals really did need a better MRSA test, but it turned out that the entire industry of clinical microbiology needed better susceptibility testing. So we thought bigger maybe from the very beginning. We may have started with what ended up being the right approach without actually running into a bit of an existential crisis along the way.

Saul Marquez:
Now, what a great story and awesome that you guys were able to just zoom out and through the work that you’ve done, see how you could focus on susceptibility rather than just the MRSA test. I mean, that’s just big. And so what would you say was the key component that helped you guys see that oftentimes we could get so myopic as business leaders and lose that? What got you guys that when you think.

Diego Rey:
Yeah, so one was, of course, looking for ways forward, given the limitations we were seeing in the initial approach. But I think what kind of let us down the right path was between starting the company and the work that we’d done prior to really any lab work on the customer development side, which led us down the path of MRSA test that between starting the company and getting to this point, we had the opportunity to do a lot more of the sort of customer development where we’ve been in a lot of credit goes to one of my co-founders and our current CEO at Endpoint Health, Jason Springs’. He’s a product guy. And so he spent a lot of time in hospitals talking with clinicians and really understanding their pain points. And so by then, we just had a much more refined view of this world right. And so I think in simple terms, it was just it was better just customer development from the get go.

Saul Marquez:
Great story. And so as you think about what you guys are working on today at Endpoint Health, what would you say you’re most excited about?

Diego Rey:
Yes. So I think thinking back actually at one of the biggest accomplishments for me, I think, was the team of extremely talented people that we were able to recruit into the company and the culture and the work environment that we created within the company. And so I’m really excited about the opportunity to do that again and maybe do it even better now that we have some lessons learned under our belt. And in particular, we co-founded Endpoint with the same co-founders from doing so. As you can imagine, we have years where we built really deep the level of trust between us and them. And one thing that was critical for our success at doing leave was bringing together complementary skill sets that covered really a lot of ground. And from what we heard about Endpoint, that’s obviously very important in our current company. And we have that between US founders. But more importantly, what we were able to do, a gene we remember doing again at some point, health is recruiting this into the company well beyond our own core skill sets. So at the end of the day, I’m just really excited about building another company with a big mission.

Saul Marquez:
I love it, man. I think about like 60 seconds every scene and Nicolas Cage movie,

Diego Rey:
Actually I haven’t.

Saul Marquez:
I mean, Nicolas Cage, you know, either love him or hate him, but 60 seconds, they like it’s totally different. But they have a band. It’s a team and they all have their specialties and they execute on what they’re doing. Specifically, 60 seconds is about stealing awesome cars, which obviously sells in Hollywood, but it’s that band of brethren and sisters that were able to make it happen.You guys are doing it again and it’s really exciting. I could hear the excitement in your voice, the talent that you guys had at GeneWEAVE and now and Point Health is just super exciting to know that groups of people like you and your team, Diago, are working on some of the toughest problems in health care for us. So so kudos to you guys for taking on the next big step in helping improve outcomes in our country and the world. Before we conclude Diago, just give us a closing thought and the best place that the listeners could get in touch with you and the team at Endpoint health care.

Saul Marquez:
So we’re currently all experiencing with COVID-19 has been a tremendous challenge for everyone, obviously. And at the same time, the amount of activity that we’re now seeing in critical care, in particular, is unlike anything we’ve ever seen before. And so I’m actually really optimistic about how this will ultimately benefit patients. And it’s really been a long time coming and in critical care. So perhaps a bit of a silver lining in the current pandemic.

Saul Marquez:
Agreed. And then if you had to point anybody in the right direction, it’s Endpoint Health, correct?

Diego Rey:
Yeah. So folks can visit us at our website, which is an endpoint.health. We also have our companies LinkedIn page and Twitter account. And if folks want to reach me, you can reach me at my LinkedIn page, which you can actually find by going to our diegoray.com or on Twitter @ Diegoaray.

Saul Marquez:
And folks, we’ll have all of these relevant links in the show notes outcomesrocket.health. You could find them there. And if you go to Endpoint dot health right at the top, there is a message from the CEO of Endpoint Health and Diego thought that would be a good place for you guys to start. It’s big, bbold letters. Read more. So a lot of ways to interact. Fantastic work being done to improve patient care. Some very interesting topics. Precision care being one of them is something that we’ll be diving more into and thinking about, thanks to Diego and his insights today. So Diego big thanks for you and the work that you and your team are doing.

Diego Rey:
Thank you very much. It was a real pleasure to speak with you today. And thanks again for having me.

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