Summary

Drew Titmarsh, Co-Founder and CEO of Dynomics, sits down with Neil to discuss the lack of innovative therapies to treat heart disease, the company’s discovery platform that uses engineered cardiac organoids that function like adult human heart tissue, and how the company is using this to develop precision therapies to address the root causes of heart failure.

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Transcript

00:00
Danny Levine (Producer)
Bioverge Podcast with Neil Littman. 

00:29
Danny Levine (Producer)
Neil, we've got Drew Titmarsh on the show today. For listeners not familiar with Drew, who is he? 

00:35
Neil Littman (Host)
Danny I am very excited to welcome Drew to the show today. Drew is the CEO and co founder of Dynomics, which is a platform driven therapeutics company developing precision cardiac therapeutics targeting heart failure. The platform is based on a proprietary cardiac discovery platform that they call Heart Dyno. Drew is a bioengineer by training and a serial entrepreneur. This is Drew's second company. He completed his PhD at the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland. He was previously co founder of Scaled Biolabs, which develops cell discovery and optimization engine to accelerate the development of cell therapies, an area near and dear to my heart. But I'm really excited to talk to Drew today about what they're doing at Dynomics for a couple of reasons. First, cardiovascular disease remains the number one killer globally and will affect over 40% of the US. Population by 2030. 

01:38
Neil Littman (Host)
However, there has really been a lack of investment in R and D for new therapies over the last several decades. And so I'm really curious about Drew's perspective. Why has there been that sort of disconnect? And then I'm excited to talk a little bit about Drew's platform and what they're doing around Heart Dyno and how that leads to development of their lead therapeutic. Candidate so, Danny, also for full disclosure, I should just mention that Bioverts is an investor in Dynomics. 

02:07
Danny Levine (Producer)
What does this platform do that wasn't either possible or practical previously?

02:13
Neil Littman (Host)
Yeah, Danny, that's a really good question. So the Heart Dyno platform has engineered human cardiac organoids that attempt to mimic the function of mature heart tissue. And so it incorporates a variety of ideologies within the organoid. So it's not just based on cardiomyocytes, for example, but it tries to recapitulate all of the various cells and tissues of a mature heart into the organoid system with the goal of being able to better predict how a novel therapeutic will respond to the human heart, obviously in clinical trials. And so I'm excited to understand sort of how they use the platform to then develop their lead product candidate. 

02:58
Danny Levine (Producer)
What's the potential here to get at the molecular drivers of heart disease and intervene before damage becomes too great to make a difference? 

03:09
Neil Littman (Host)
Well, Danny, that's the billion dollar question. I mean, I think there's huge potential here to look at a variety of either genetic diseases or a variety of different diseases within the broader category of heart failure. And I'm going to ask Drew about some of the nuances there, but I think there's a lot of potential. I'm also really excited to get Drew's perspective on his thoughts around the recent data from some of the novel obesity drugs that have been approved. Wagovi, for example, was just reported to have slashed the risk of serious heart problems by 20% in a very large clinical trial, right? So these drugs that were initially targeting obesity have been shown to be great drugs for serious cardiovascular problems. And so how does that change the standard of care? How does that potentially change what dynamics is doing? So I'm really excited to get his perspective. 

04:01
Neil Littman (Host)
But all that aside, I think Dynomics approach is slightly different. And to your point, they're looking at some of the underlying molecular drivers, and they're looking at different categories within heart failure, like dilated cardiomyopathy. And so I think there's obviously a lot of room for improvement. There's a lot of room for novel therapies that are not just masking the symptoms of heart failure or heart disease, but are treating the underlying root cause of those diseases. 

04:29
Drew Titmarsh (Guest)
Well, if you're all set, let's do it. 

04:31
Neil Littman (Host)
Danny, Drew, thanks for joining us on the show today. I'm incredibly excited to welcome you and have a discussion about what you're doing at Dynomics. 

04:42
Drew Titmarsh (Guest)
Great. Thanks, Neil. It's great to be here with you on the show. 

04:45
Neil Littman (Host)
So, Drew, as I just mentioned, we're going to talk about the company that you co founded, Dynomics, your discovery platform, and your efforts to develop precision cardiac therapies to treat heart failure. I always like to start from the 30,000 foot vantage point, and so let's start with heart failure, which it sounds like it would be pretty self explanatory, but there's lots of nuances here, so I want to make sure that we're on the same page. Let's start with how do you define heart failure? 

05:17
Drew Titmarsh (Guest)
Yeah, well, you're right. It sounds pretty self explanatory. And so heart failure is really failure of the heart to perform its normal function, which is, of course, to pump blood around the body. Now, that sounds like a broad definition, and it is. And it's what we've historically and used and what we currently use to describe actually millions of patients in the US. That really have an insufficient or abnormal heart function. But within that, there's actually a lot of heterogeneity in terms of the etiologies that underlie those patients'diseases. And so to define it properly should actually take a little bit more nuance. And I think that's actually where we're seeing some interesting trends towards a deeper understanding of this disease and moving towards a sort of precision cardiology. 

06:05
Neil Littman (Host)
So, Drew, I want to come back to the biology here of heart failure in a minute, but how big of a medical problem does heart failure represent today? 

06:14
Drew Titmarsh (Guest)
Yeah, it's a really significant problem, Neil. So heart failure, it's really a significant proportion of overall cardiovascular disease and that big bucket cardiovascular disease overall, that's the biggest killer globally, and it affects something like 40% of Americans. And so looking specifically, though, at heart failure, it's still a really big patient population here, and it affects about 4% of Americans, and then there's some subgroups within that. And so if we look within heart failure, there's a lot of these sort of specific heart conditions which we can understand a bit deeper, say, precision diseases like dilated cardiomyopathy or hypertrophic cardiomyopathy. And these are sort of leading causes of heart failure, and they represent significant patient populations as well. So each of them can be about as prevalent as one in 500 people to maybe one in 200 people. 

07:13
Neil Littman (Host)
And we'll come back to dilated cardiomyopathy here in a minute because I know that's your lead indication. But heart failure isn't something that happens suddenly. So can you talk a little bit about how it manifests itself and how it progresses over time? 

07:28
Drew Titmarsh (Guest)
Yeah, so I think there's two ways to look at that, actually, and one of them is really that risk factor based view of how heart failure manifests. And definitely that's coming from our understanding of how things like obesity then can lead to diabetes and cardiovascular disease. And that really came from looking at these maps of prevalence that really just overlaid very tightly with each other. And these regions that would have high levels of obesity would then progress to diabetes and cardiovascular disease. And so this is one area where I think there's been some great progress made, but it's a bit more complex than that, actually, because there are also cases where a heart failure situation could come sort of out of the blue. So someone with a genetic mutation in one of their cardiac genes may be carrying this, and it may not present until adult life, but it may present very suddenly. 

08:32
Drew Titmarsh (Guest)
And there's a risk of sudden cardiac arrest, for instance. And so it's more complex than just age or these risk factors or these lifestyle choices, although they're significant contributors, but there's a lot more sort of richness in what's happening that we really need to tear apart. And so overall, these are conditions that affect the heart's function and left untreated, they can progress to heart failure. So once you have heart failure, that's really a kind of dismal situation. The prognosis is not very favorable. There's very few therapeutic treatment options. Most of our treatments are just symptomatic, and they delay progression of the disease. And so given that we have more information than ever on some of these genetic causes of heart disease, there's also an opportunity to intervene earlier, not just treating the risk factors, but treating actual molecular drivers of the disease. 

09:35
Neil Littman (Host)
And Drew, I want to dive into a couple of your comments there. I mean, you were referencing the standard of care, so I want to understand sort of the standard of care for heart failure these days. And as you mentioned, it's largely treating the symptoms and not the underlying root cause of the disease. But you mentioned another really interesting point, which I just have to dig into here, and I don't want to go off on a tangent too much, but you had mentioned cardiovascular disease and heart failure being a comorbidity with obesity. There's been a lot of recent news lately about the new obesity drugs, particularly wagovi around its ability to reduce the risk of serious heart related problems by about 20%, which was indicated in a very large clinical trial, the results of. 

10:17
Drew Titmarsh (Guest)
Which were just reported. 

10:18
Neil Littman (Host)
What are your thoughts around Wegover or some of these new obesity drugs in terms of how they relate to the cardiovascular problems that we see out there in the US. And globally today? 

10:28
Drew Titmarsh (Guest)
Yeah, thanks for the so I think this is a really important progress that's been made around part of the problem. This is not a cure all, but it's extremely encouraging that we're finally having enough insight to be able to intervene in that axis that I just talked about, the obesity, diabetes, cardiovascular disease axis. And so, like you said, these are very big trials where we're looking at large populations and we're looking to sort of mitigate these risk factors and look for these long term outcomes. And I think that's where it's really promising that we've seen some great data and that will continue to evolve. What I think there are a couple of drawbacks there and there's been enough sort of commentary of that in the media, but I think it's very encouraging progress. But one thing I think we do need to remember is that we can't just treat a risk factor and we need other ways of getting at heart disease and different forms of heart disease where there's a deficit in the heart function. 

11:38
Drew Titmarsh (Guest)
And someone who may already have heart failure or they may have a genetic form of the disease and they need to see something that can target the heart and increase the function of their heart and give them a benefit in that way. And that's just really where this sort of traditional view that's based on sort of physiology coming out of research from the that's where I think we've missed a little bit of opportunity and there's this great opportunity for us to really define and segment down the disease more and provide those targeted treatments that can create benefit. 

12:16
Neil Littman (Host)
So, Drew, I want to pick up on that thread for a minute. In terms of missed opportunities, we have not seen the same level of innovation and R and D spending in the development of therapies for heart disease relative to the need as we have for other areas like cancer. Why do you think that is? 

12:35
Drew Titmarsh (Guest)
So I think the cancer analogy is a really good one here and let me come back to that. But really I think this has been driven by just a historical lack of molecular understanding of what's going on with heart function. There's been a dearth of therapeutic targets that can be developed. And really, I think this has led to that paradigm of heterogeneous patient populations, large, inexpensive and long clinical trials and looking for outcomes based data. And for that reason, it's just been an unfavorable area for a long time for both pharma and venture capital investment. But if you look at the numbers, this is an area that remains highly underinvested relative to the healthcare burden and the opportunity. But we are now starting to see signs of that changing slowly but surely. But looking back on that historical paradigm, it's really been a lack of viable drug targets. 

13:36
Drew Titmarsh (Guest)
So of those that are approved on market for heart failure, half of those targets are actually shared with hypertension. So they weren't actually directly targeting the heart and improving its function and they had these other systemic effects. And then a couple of years ago there were probably only 20 to 30 more drug targets in development. But the latest trend that we're seeing is there's this progress that's being made towards the clinic. And I think we're on the cusp of realizing the potential of precision medicines and particularly genetic medicines for heart diseases. And we're seeing a sort of first wave of these precision medicines enter the clinic, and it's really riding off some of the success of companies like myocardia with their drug Mavicantin, which was a precision treatment that was successful and then was acquired by. And so I think this is where things are going. 

14:38
Drew Titmarsh (Guest)
And like that cancer analogy, we're moving away from this undefined idiopathic disease, which cancer used to be towards a more molecular functional driven understanding of the disease. So just like with cancer now we have this huge explosion of immunooncology which I think really came from understanding the functional interaction between the immune system and cancer. And I think we're going to undergo this same transition in cardiovascular disease towards molecular understanding and functional understanding and how we can intervene helpfully there. 

15:12
Neil Littman (Host)
So Drew, that's a great jumping off point then to what you're doing at Dynomics and how you're approaching things a little bit differently to better understand the heterogeneity of heart failure and some of the nuances around the biology. And so you have developed a proprietary discovery platform called Heart Dyno. Can you explain what that platform is and how it helps you to make better decisions when it comes to developing therapeutics? 

15:39
Drew Titmarsh (Guest)
Absolutely. So we really see this discovery platform, heart Dyno as the key to unlocking that future that I just sort of talked about there. So Heart Dyno, it's our proprietary predictive discovery platform and it's really based on these mature and functional human cardiac tissues that we can build in the lab. And it's really based on 15 years of R and D groundwork in order to get them to be industry ready. And so there's a couple of things about these miniatured tissues that really make them useful for shining light on heart function and heart disease. Number one is that we build them using an authentic composition of diverse cardiac cell types. So we generate them using stem cells, but it's not just a cardiomyocyte. So the muscle cell of the heart, this is more of a mix of cells that come together and form heart tissues. 

16:35
Drew Titmarsh (Guest)
So we see them self assemble and they self pattern and we really feel this is an authenticity that reflects a lot of the human heart biology. Second point is that we've really put a lot of work into making sure this is a mature model that can have characteristic functional responses as per adult tissue. So getting mature models has been a big challenge with these stem cell derived cells and tissues. We've made a lot of groundwork on that and can really we're reflecting more and more of the adult human heart biology that's known. So the third point is that we've really scaled these. So this is a scalable and uniform model system. So the tissues are about 1 mm in size, they have about 60,000 cells in them but we can create these in batches of several thousand at a time and really very uniformly. So 95% of the tissues would form well and pass our baseline QC and this is really a break from other systems that we've had access to things like engineered heart tissues. 

17:44
Drew Titmarsh (Guest)
So they've been great for sort of limited studies where there's an existing lead drug looking at toxicology and they really respond very well for that. But throughput has been a problem and now this is where with Dynomics and heart Dyno, we're breaking through into that discovery screening scale and that just opens up so much that we can do around phenotypic screening of drug libraries or genetically directed knockdown screens. And so that's what we've been churning most on to come up with the best insight. 

18:17
Neil Littman (Host)
Going back to the cancer analogy, there's a lot of talk around the tumor microenvironment. And so my question to you, Drew, is what's been done to validate the platform and how predictive, I guess what I would describe as the organoids that you've developed are in terms of how the human heart would actually within the human body or in that sort of, I guess for lack of a better term, microenvironment. 

18:43
Drew Titmarsh (Guest)
Yeah, great question. So I think with the cancer analogy, one of the things that drove the immunooncology was really that molecular level understanding from a lot of the sequencing type work but also it was these functional cell assays. So putting tumor cells together with immune cells and looking at the functional interaction and I think that's similar to what we're doing, we're placing this really central as our functional representation of the heart. But what biology are reflecting and how have we sort of validated that? So firstly, I'll say we've published pretty widely on this but you shouldn't just take my word for it. So I think that the three best pieces of evidence for validation are external collaborations that we've undertaken and this has really validated the insight that the platform can provide. So early on, right as were incorporating the company, we published a study with a top 20 biopharma company focused on cardiac regeneration. 

19:43
Drew Titmarsh (Guest)
So this is an area where we're looking to have the heart muscle cells grow and replace themselves and it's been really difficult to get things that translate. But what were able to show in this collaboration was screening of that partner's chemical library and we rejected a lot of the false positives that emerge from immature systems to really select the two things that translated in vivo. So that was a really great proof of concept showing that we could rapidly discover the right thing. Next example from that is really just after we incorporated the company we had this COVID-19 pandemic which was really intimately correlated with heart disease. There were a lot of reports of all the serious ICU patients having these heart problems. And so we very rapidly spun up a model of that cardiac inflammation and we discovered drug targets that were mediating that dysfunction in the heart. 

20:43
Drew Titmarsh (Guest)
We were able to screen existing drugs in development that were relevant to that target. And with an industry collaborator on that work were able to identify one of their drugs that they actually opened up into a phase two clinical trial based on that data. So this was really global emergency to phase two trial opened within twelve months and I think it was just an excellent validation of the real world insight that the platform could provide. One last example on that is breaking more. So that's sort of an environmental disease model, but we've also had some success with a current partnership surrounding genetic disease. So that's where we're using genetically mutated stem cells in order to create these tissues. And so I think that's another area where we've published and also have some unpublished work showing that it really works very well for modeling that. 

21:40
Neil Littman (Host)
So Drew, what I was going to ask is you're obviously using your model system to go after a variety of different forms of heart disease. And so this leads to my next question is how well are you able to create organoids that model these different conditions? 

21:58
Drew Titmarsh (Guest)
So I think that question, the only way to answer it is by accumulating enough data to sort of prove that the model you've created is useful. And so there's a number of ways we can come at that, but just in terms of the types of conditions we're trying to model. So like I said, a lot of heart failure is driven by these environmental factors and risk factors like loading on the heart, diets, inflammation and so forth. And so we've got a number of models that we've built using heart Dyno where we can induce those disease phenotypes using really relevant stimuli. For instance, we might have a dietary type insult and then we see a dysfunction in the heart and can learn about the molecular interactions underlying that. The COVID-19 inflammation type model was an example of that. But like I said, the environment, it's only part of the picture and going more towards a precision medicine paradigm. 

23:02
Drew Titmarsh (Guest)
We can also construct genetic models. So that's where we start with either patient derived cells that have a specific mutation, which we can then create a control line from that by correcting the mutation. Or we may simply start with a research grade stem cell line and introduce different genetic mutations. And so we've had great success with that approach, where we've got a number of genetic models that actually reflect a lot of the clinical phenotype of those specific genetic diseases. And going one layer deeper, we can actually combine both those genetic and disease models in one experiment. So that really allows us to probe heart behavior and look at some of the environmental insults that may unmask some of these genetic diseases, for instance. 

23:49
Neil Littman (Host)
So, Drew, I want to move forward and talk a little bit about your pipeline. You have a lead experimental therapy, Dyn 101, which is in development to treat dilated cardiomyopathy and heart failure. Can you first explain what therapy is? And then I want to go back and link the platform to how you came up with this as your lead therapeutic candidate. 

24:14
Drew Titmarsh (Guest)
Right. 

24:14
Neil Littman (Host)
How did the model inform this drug, and how did you decide on this drug to move forward? But let's first start with what it is. 

24:22
Drew Titmarsh (Guest)
Okay, so Dyne 101, it's one of Dynomic's potential lead programs. And Dyne 101 takes a novel approach to restore or increase heart function in diseases like dilated cardiomyopathy or heart failure with reduced ejection fraction. And so these are diseases that share this common mechanism where the heart is not contracting enough during systol, and so that's where it's expelling blood from the heart. And so were looking for ways to intervene there to specifically improve that contractile function of the heart. And so Dime 101 is a sort of advanced therapeutic modality that reduces expression of a novel target that we found to be involved in that. 

25:07
Neil Littman (Host)
Andrew, what have you done to date with the compound? What studies have you done or what have you done to sort of validate this as your lead compound, as opposed to I'm sure you had a bunch of other potential leads in the pipeline. 

25:21
Drew Titmarsh (Guest)
Right, so there's a sort of multilayer filter that we've built at Dynomics, and it centers around heart Dyno, but there's many layers to it. And so Dyne 101 actually came from a broader starting opportunity set of 216 gene targets that we had shortlisted using Bioinformatics. And this is based on ten or 15 years of bioinformatics, which we accumulated and looking for the targets that were our best bets on being involved in heart maturation and development of function and some other things like being conserved in mouse and human and also enriched in human DCM hearts. And so we did a lot of screening of a library knocking down each of those genes, and Dyne 101 emerged as one of the strongest candidates coming from that. But since then, we've then gone and validated that target by looking in some of these larger data sets of interest, some of these population level studies that track genetic variation and clinical presentation. 

26:33
Drew Titmarsh (Guest)
But the next level up is that we really go to our human tissue model very early on during discovery. And so we validated that knocking down this target specifically improves that heart function in heart Dyno. So since we had that very encouraging data, we progressed to in vivo studies, and were working with a non genetic model of heart failure in a mouse. And in a pilot study, we saw that were able to engage that target and knock it down. And doing so caused a positive trend on cardiac function. And so that really galvanized us to move that to a longer term five week efficacy study in that model. And during that, we saw that administering dime 101 created a significant beneficial effect on heart dilation. And so, just like it sounds, heart dilation is a key hallmark of dilated cardiomyopathy, and it's where the heart sort of enlarges and it weakens in its capacity to pump blood. 

27:37
Neil Littman (Host)
Drew, you had mentioned Dyne 101 is a novel therapeutic modality. Have you disclosed publicly what that is gene therapy? Is it AAV? Is it some other gene therapy? 

27:47
Drew Titmarsh (Guest)
We haven't for Dyne 101 because we're in the process of nominating the clinical candidate for that. And so we use a number of different tools to come at that during our discovery and development processes. But hopefully soon we'll be able to share what the clinical candidate looks like for that. Got it. 

28:04
Neil Littman (Host)
Okay, great. So let's pivot a little bit, and I want to talk about your business model. Probably hazard of me formally being in the sort of business development profession for many years. I'm always fascinated with different business models, obviously from the investor standpoint as well. But are you considering sort of building an integrated biotech company, developing your own therapeutics, moving them through ID, enabling studies into the clinic through clinical trials? Are you considering a partnership model where you're using the platform to spin out a bunch of different assets that you then partner? How do you think about sort of capitalizing and creating the most value for the company? Because you are fundamentally a platform technology that could theoretically spin out a bunch of different assets. But then, of course, if you're focused one, you need to really focus on advancing that one. So I'm just curious how you sort of think about the different pathways there. 

29:01
Drew Titmarsh (Guest)
Yeah, it's a really important question, Neil. And clearly, we deeply believe in the value, the ultimate value that the heart dyno platform could create. And so for that reason and the fact we invested so much time in developing it, we really want to keep that as an engine that can drive Dynomics to new heights. And so based on that and also based on experience from a previous startup that had a big platform angle to it. We made the decision early on in this company that huge value in this space and meaningful impact on cardiovascular disease could only be created and captured as a full stack therapeutics company that uses the platform for itself. So we deeply believe in that. And so thesis of the company's business is really to develop and transact assets, but there's a small asterisk there and that last sentence is really broadly defined. 

29:58
Drew Titmarsh (Guest)
And so we're going after clinically tractable therapeutic programs that we can develop ourselves, but we're also open given the immediate impact that we think we can create with the platform. We're open to select partnerships that have very high strategic alignment with where we're going, where we can partner early on and that asset might actually be defined as a novel target or even a novel disease model. And so there is a bit of flexibility where I think there can be shared value and I think this just provides even more validation and signal for this platform and also the types of therapeutics that it can generate and derisk. And so ultimately in order to make the biggest possible impact on cardiovascular disease, we're going to have to work with bigger players that are in different types of biology and have the heft to go after some of those large clinical trials and so forth. 

30:52
Neil Littman (Host)
Drew, I can't help but want to ask the question that I typically like to ask on this podcast is this concept of tech bio versus Biotech. You're out here in the Bay Area, there's sort of a big movement of tech bio, however you want to define that, versus traditional asset centric, company creation biotech model. It's almost like west coast versus east coast to some degree. How do you think about sort of tech bio versus biotech and do you relate more to one than the other or do you think the nomenclature is really sort of merging in this day and age? 

31:27
Drew Titmarsh (Guest)
Well, it's funny, I went to an in person sort of fireside chat on this and I think most people were they'd had enough of the debate and simply wanted to focus on doing the best science and making the best impact. 

31:40
Neil Littman (Host)
I agree with that. 

31:41
Drew Titmarsh (Guest)
So what I can say to it though, is that we clearly view ourselves as multidisciplinarians. So we need platform technicians as well as industry, experienced drug developers in order to realize our vision. And so that's where I think the magic is. If you can connect that depth of opportunity and that font of future value that comes from having a deeply technical platform with the people and the team that are able to crystallize that value into highly valuable and transactable assets, I think that's really where the business opportunity for the company lies. And that's the type of company we're building.

32:20
Neil Littman (Host)
Yeah. No, I love that. And actually that leaves a follow up question. I. Have, I think. Rightly, so all of us focus on the science, on the technology, but you're a serial entrepreneur. This is, I believe, your second company that you've co founded. Culture plays an extremely important role in building successful companies. It doesn't matter what industry you're in, but it's all about the team. It's about the culture and the environment that you foster. How do you think about the culture of Dynomics and is there anything in particular that you do to foster the type of culture that you want at the company? 

32:57
Drew Titmarsh (Guest)
Yeah, great question. Clearly this is key. We can't just have good science. We want a great place for people to work at Dynomics. And one thing that was sort of working in our favor was that the co founders had really worked together on different aspects of the platform or the company over sort of 15 years. So there's a really high level of trust starting out with that. Secondly, like you said, my experience with my first startup gave me a couple of learnings that money can't buy at business school and really sort of forged how we think about dynamics. But I think the most important one was recently we had a whole of company retreat and we split into three different teams that cut across the vertical and sort of asked, what do you think are the core values of dynamics? And every team actually came back with the same set of three to four answers. 

33:55
Drew Titmarsh (Guest)
So I think were already sort of mentally aligned on what those are. And so we have a deep focus on sort of multidisciplinarianism integrating different types of ideas and also disparate types of data and then taking a sort of data driven and data infrastructure approach to building the answer, but then also in a way that translates that into real life changing value for patients living with heart disease. And there's a few other smaller ones, but those are the key tenets. And that's where when you have different people with different skill sets, we're all latching onto those same things and working towards the same goal. 

34:41
Neil Littman (Host)
Yeah, no, I think that's really critical. 

34:43
Drew Titmarsh (Guest)
Right. 

34:43
Neil Littman (Host)
Making sure that everyone's in the boat rowing in the same direction. Just out of curiosity, Drew, in terms of the team breakdown, is it mainly biologists and chemists or do you have software and hardware engineers in the mix? How does that sort of break down? Yeah, so we try to cover all. 

35:01
Drew Titmarsh (Guest)
Bases, but we cover them sort of with different levels of coverage. As an early stage company, but we are heavily represented on the sort of platform technology, the Bioengineering, the know how of how we deploy this platform. We've then complemented that with our CTO, who is full time focused on building the software infrastructure that supports us. And so we have a cloud software platform that's built to tech industry best practices and it accumulates all of this data in the same structure and builds this ongoing data asset. And so we complement that with bioinformaticians that work with that data platform in order to build supporting data for our programs. But it's led as well by industry, experienced therapeutic developers and also our CSO, who's been involved at every stage from sort of consulting to large pharma, mid cap pharma and even cardiac biotech startups that have been IPOed and acquired. 

36:10
Drew Titmarsh (Guest)
So we're building up more, and I think, like I said, Neil, as a multidisciplinary company, you need all types at the table and including business folks as well, that get deals done. And so, yeah, we expect to bring on lots more different people that agree with our mission and our values, and I think I'm excited by it. 

36:31
Neil Littman (Host)
And Drew, since we're talking about company building, you've been successful in raising capital from Mayfield and boost VC in your last round. You've navigated a changing economic environment, particularly within the biotech space where times were pretty frothy. Now times are the opposite of frothy and are pretty dire out there when it comes to trying to raise capital. We have a lot of entrepreneurs who listen to this show. Any advice for folks that are either raising capital now or need to raise capital in the relatively near term? And how has your experience changed from raising capital in good times to the current environment? 

37:11
Drew Titmarsh (Guest)
Yeah, I think the thing that doesn't change is that it's about grit and resilience and just staying the course through good and bad and really focusing down on building the best business, because building the best business is really the catalyst that will move all of those other things forward during good times and bad. So we're funded to date with venture capital, and we're very lucky to have an amazing top tier firm and also partner that has been and continues to be anchor investor in dynamics. And that's really built on a deep personal relationship of trust as well. And so we hope to be able to talk about that more in future. But we've accumulated some other folks as well that have joined our mission and sort of have different superpowers, if you like, in the ways they can help us out. And so for me, it's always about being resilient and keeping that network of relationships strong and active, and we all help each other out to get through this. 

38:13
Drew Titmarsh (Guest)
And so while we're preparing for our major next round of financing, we've also seen a significant uptick in revenue generation, which I think is just a positive symptom of the business that we're building. And it's been very positive for signaling as well. So we're comfortable with the way Runway is, but also looking to expedite in the best way possible our mission of bringing precision therapeutics to patients suffering from heart disease. 

38:41
Neil Littman (Host)
Well, Drew, I think we could probably talk for another couple of days about some of these dynamics. I find it endlessly fascinating, both on the science and the business front. But I do want to be cognizant of your time and wrap up and say a big thank you for joining me on the show today. 

38:56
Drew Titmarsh (Guest)
It's been a pleasure. Thanks so much for having me. 

39:02
Danny Levine (Producer)
Well, Neil, what did you think? 

39:03
Neil Littman (Host)
I thought that was a really great discussion with Drew. I was excited to hear a little more about the heart dino platform and why it's different. Organoids are nothing new. They've been around for a long time. Some are more successful than others in recapitulating human organs and tissues. I think what Drew and Dynomics is doing is really interesting in terms of trying to incorporate the various types of mature heart tissue into their organoid as a predictive way to come up with novel therapeutics. You heard us discuss Dyne 101, which is their lead therapeutic candidate. He's not giving out too many details publicly about what that actually is, but it certainly sounds that they were able to leverage the platform to come up with a lead asset that they are moving forward. They have some pretty compelling validation, early validation for Dyne 101. And I think if the platform works as intended, dyne 101 could be the first of many assets that they sort of spin out and start developing. 

40:07
Neil Littman (Host)
And you heard you and I talk a little bit about the business model and all those intricacies, which I'm not going to rehash here, but I always love learning about the different business models and how an entrepreneur thinks about the various paths that they could take to build a successful biotech company. 

40:22
Danny Levine (Producer)
You talked about the lack of progress in treating heart disease relative to indications like cancer. Drew indicated we're now moving into this era where precision medicine is going to be enabled to treat these kinds of conditions. How do you see this area of medicine changing? 

40:40
Neil Littman (Host)
Well, hopefully it moves more toward the field of how cancer has developed in the sense of developing novel, precision based therapies. You heard Drew and I talk a little bit about some of the analogies to cancer therapeutics, and those have become very precision based because we have a much better understanding of the underlying biology and genetic drivers of many forms of cancer. For whatever reason, the biology has not been as well understood. It sounds like within the realm of heart failure, and we didn't get into too many of those details, but it sounds like we're now sort of catching up, and a lot of the molecular drivers of some of these underlying conditions are being better understood. And so I think that has really allowed Drew to develop this heart Dyno platform with his colleagues at Dynomics. And maybe we will be moving into that error, precision based medicine within cardiovascular disease and heart failure because it has really lagged, even though it's the number one global killer around the world. 

41:42
Neil Littman (Host)
And so it's been puzzling to me why there hasn't been more R D investment, but maybe it comes back to sort of a lack of understanding of the biology. Or you heard Drew talk a little bit about some of those challenges. 

41:53
Danny Levine (Producer)
Well, this is a company with a unique discovery platform. How big an edge do you think this provides dynamics? 

42:01
Neil Littman (Host)
Well, I think it can provide a very big edge. I think the key will be what do first in human clinical trials look like for their lead asset. 

42:10
Drew Titmarsh (Guest)
Right? 

42:11
Neil Littman (Host)
I mean, they have a lot of early validation. All signs are super positive in terms of what they've done and developing a lead compound. But the proof is human clinical trials and making that translation from what they're seeing in the organoid models to how patients actually respond to the drug. So it's exciting. It's promising. I think the data is very compelling, but the proof will be how patients actually respond. So we're not quite there yet. 

42:37
Danny Levine (Producer)
You didn't want to take a deep dive here on business models, but one of our recurring themes is particularly around platform technologies, is how to best get value out of that. This is often a balance between the platform or building your own pipeline. What do you think about their approach? 

42:58
Neil Littman (Host)
Yeah, I think they have a measured approach. Right. You heard Drew talk quite a bit about how he thinks about the business model. You heard him mention at the end that they're generating revenue now. And so we've seen a lot of companies that have sort of pivoted in this challenging fundraising environment to focus a lot more on business development, bringing in non dilutive revenue through. So, you know, Dynamics sounds like they've been doing that and have been successful doing that. And so from a purely investor standpoint, that's great. Right. That helps to extend their runway. It's less capital that investors have to bring to the table, and it also helps to validate their platform so those types of partnerships can help catalyze a next round of financing as well. So it sounds to me like they're doing all sort of the right things. And you heard us talk a little bit about the differentiation excuse me, of tech Bio versus you know, I think Drew had a really relevant point in the fact that it's really about the patient. 

43:59
Neil Littman (Host)
At the end of the day, some of this nomenclature is a distraction, but it is important because it does also talk about the culture and how companies are being built. So it is important to talk about, but at the end of the day, we need to remember as an industry that the patient is the North Star, and absolutely sounds like that Druidynomics has that perspective sort of well in hand. 

44:20
Danny Levine (Producer)
Well, until next time. 

44:22
Neil Littman (Host)
All right. Thank you, Danny. 

44:26
Danny Levine (Producer)
Thanks for listening. 

44:27
Danny Levine (Producer)
The Bioverge podcast is a product of Bioverge, Inc. An investment platform that funds visionary entrepreneurs with the aim of transforming healthcare. Bioverge provides access and enables everyone to invest in highly vetted healthcare startups on the cutting edge of innovation, from family offices and registered investment advisors to accredited and nonaccredited individuals. To learn more, go to bioverge.com. This podcast is produced for Bioverge by the Levine Media Group. Music for this podcast is provided courtesy of the Joan Levine Collective. All opinions expressed in this podcast by participants are solely their opinions do not reflect the opinion of Bioverge, Inc. Or its affiliates. The participants'opinions are based upon information they consider reliable, but neither Bioverge or its affiliates warrant its completeness or accuracy and it should not be relied on itself. Nothing contained in accompanying this podcast shall be construed as an offer to sell, a solicitation of an offer to buy, or a recommendation to purchase. 

45:35
Danny Levine (Producer)
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