Why Heart Failure Drug Development Needs Smaller Trials

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0:00 In medtech, the difference between a good quarter and a great one isn't always the product. It's the friction standing in the way. Broken sales cycles, misaligned teams, deals that stall at the finish line. Every leader feels it, and the best ones know how to remove it. Welcome to Zero Friction, the podcast where we go inside the minds of MedTech's top commercial leaders to uncover the real barriers they face, the decisions they make, and the systems they build to keep the revenue moving. I'm your host Terry Coutsolioutsos. Let's remove some friction.

Well, welcome audience. My name is Terry Coutsolioutsos. I'm with the Zero Friction podcast. Today I have the honor of speaking with Ayla Annac. She is the co-founder and CEO of Invivo Sciences, which is breaking out with a brand new therapy for treatment of heart failure. And Ayla Annac is here going to give us a little background on her career, talk about some of the opportunities that she sees in the heart failure marketplace and where Invivo Sciences will be moving towards in the near future. So Ayla Annac, thank you so much for being here. Why don't you give us a little background on yourself and the company. So thank you.

Thank you Terry. I appreciate being here as your as your guest and appreciate the opportunity that you bring to us. My name is Ayla Annac as you mentioned and I am a co-founder and CEO of a smallcale biotech company called Invivo Sciences since 2001. My co-founders Dr. Bakasuki and Dr. Elliot Alson we established the company initially in St. Louis, Missouri and the the company started as a technology development company for enabling the precision medicine in heart failure and the part of the technology that we developed or platform we develop combines AIdriven patient stratification with patient specific biological heart tissue that we create three-dimensionally and what we call biological tins. So very layman ways that we are able to to get a sample through the stem cell technology from a patient or patient specific and create the outside of the body the three-dimensional heart tissues or disease models and we are able to screen the drugs or targeted drugs on those uh patient specific human cardiac tissues

And we are able to identify not only targets but also toxicity of those molecules for the target population and through AI integrations out of a large scale of population we can even go to the sub categories of the population that means we can do smaller scale clinical trials for the heart failure precision drugs and that is not very available yet in industry and that is why we are excited to do but when you ask how I came to this world is that question I will go back stuck from where we are We I lost my own father to heart failure in Turkey in Istanbul long years ago more than 33 years ago. He died at work at age 53 for heart failure. And it was very difficult as a young child and a family to understand why he died suddenly at work and it was very young man. And this became a mission in myself and in my heart and I said I want to

3:22 Make something happen so that nobody experience this pain and nobody uh go through this again and I didn't know that time how big of a scale of a disease is heart failure around the world and when I talked to the doctors at that time for my father when we went to visit the the doctor they told me that there's no technology available he needs a new heart and there's you know millions millions of people in the line to get a heart. We we cannot he needs to be in a list. He will not make it. So such a uh information for a little mind is very hard to grasp. Later on in St.

Louis, Missouri when I was working for uh Nestle Pina and I had the pleasure to meet with the two scientific founders Dr. Vakasuki and Dr. Elliot Alson and their project. I was very excited because they were talking about to create from the human heart directly by the utilizing stem cell technology which they have which is creation of threedimensional cardium to screen the drugs and to be able to identify precision approach utilization a drug that is curing or at least targeting the disease underlying disease of a specific patient population. And they said they can they can help to do so. And that excited me when I was working for a corporate and I said I like to help because I lost my father. I can help you to put the business side of it, business plans. And I talked to the Washington University medical school and suddenly medical school said that oh this is very nice but you need to take on because we need somebody to lead the project and if

You lead that if you put together the business plans and the concepts and if it is you know reasonable then we fund partially and the scientists can go you know apply for grants and we see the scientific validation and it goes I didn't know that it will take a very large years and I didn't know how difficult It will be to get funding to validate scientific standpoint to get NIH and American Heart Association's validations behind and these are different paths and they come together but you have to validate each step and then go to the pharmaceutical companies like Fizer that time to see if they have an interest but that time they said we are ahead of time we need to you know develop and then bring them as we develop more concept to you know stage of the data and platform technology. So they they kind of guide me with the sets of paths but each path takes years and require investment. So these are heft technologies require funding and require a consistent

6:07 Effort of promoting and not giving up on the technology till development stages and everything is proven data came. So teams cannot give up even though people are not there to match with your excitement or you have some solution but they are saying oh I I need data or nobody is doing it this is ahead of time. Many people responded that way and investors were not excited to invest things early stage or too risky. So we have only groups like SPI government grants that they fund early risky technologies or universities. So we were in that gap and now we had to persevere and have loss of grit. So I think uh the way I came into that because of loss of a father had a mission and the the scientific partners also are idealistic and really really sharp individuals that they also want to help humanity. So they have this humanitarian aspect of it because they do know that it's a difficult path. If heart failure had a solution by now my father died 34 years

Ago many many drugs will come right now there is still no precision medicine in the heart failure even though it is number one killer and 20 million people each year dying from that and so I think the reason I did it is very simple I would like to be a solution to a really large scale problem and I also understand that this is big so I will I would like to be more leading the collaborative effort because no one company can make this happen. You need pharmaceutical partners, you need investors, you need experts, you need people understand how difficult space is this uh oncology has been supported, precision medicine in oncology has been supported with the large scale government funding and many people's efforts and right now more than 500 drugs available, precision drugs available. Oncologist space is a precision medicine approach but heart failure is five or six drugs for all around the world and no precision medicine yet and no funding equivalent to the oncologist space.

So do those drugs actually cure heart failure or do they just um fix the symptoms or or provide a solution for the symptoms? Is there is there a cure or is it cure? Secondary symptom management is the right now they are providing a quality of life for the patient. Maybe they can relax, they can breathe and maybe they can walk, they can sit on a chair and they can read things but none of them is curing. So they are becoming in the medical system and in the area that we are working heart failure preserved ejection fraction is one of the most debiliating one rehospization occuring. So they are at home they cannot exercise even because there's no drug there's no innovation in the space and that rehospization cost is enormous without curing the patient you know I think it's a real good place to maybe even highlight like what is the impact of heart failure on our society today like so there's obviously the qualitative component of somebody's life right so when you get heart failure you

9:25 Can barely walk down the street you know a prost the house, play with your children, play with your grandchildren, get to the mailbox, right? Those types of things are those activities are taken for granted that they just don't happen with the same quality that you used to have. Correct. I think you you really uh well explained not able to play with your grandchildren, not able to go to the mailbox or exercise as a man or not able to breathe correctly and you are dependent on someone else because you know our societies you know man has been providing for the family and when you take that main provider sometimes there's not much left for that society.

Some people go into poverty levels when the main uh main uh figure can no longer work in the in the area of what we work the rejection fraction 51% is female. The situation is much more worse because at least in the male figure when they go down there's a partner, there's a sister, there's someone that's fe feminine caregiver, but caregiver, right? A caregiver. Careiver and it's a big burden on the caregiver because they are not sometimes even compensated. But if the care taker or the needer is a feminine now somebody needs to work male the person who's not the the natural caregiver now that needs to be the caregiver it's hard right it is 51% that means our society can collapse if this heart failure is not going to be having a solution nobody looking into that from that standpoint both is not good idea but if there's no solution and Both genders are affected in this long-term effects on our communities is disastrous. So we need to understand maybe being a cancer patient

Is not a fun thing. Nothing is fun in any way. But heart failure you cannot breathe. You have one heart. The moment you stop breathing it is done. And so the other thing I think our audience you know highlight for is that you know I think heart failure has the same mortality rate of a lung cancer. So I think you know the mortality rates what five 50% within five years or something along those lines. Correct. Exact. So catastrophically you know from a mortality perspective is there economically I think it's the number one health care cost burden that we have on Medicare. So when you look at our Medicare spend I think heart failure has the number one expense tied to it. So the problem from a qualitative life perspective is huge. The problem from a mortality perspective is huge and the problem from an economic perspective just with the health care cost is huge.

12:12 So the problem's massive. So you're you're out here trying to fix this this massive problem and so and your solution is is designed to be a curative solution correct as well. Yes. The two area we are helping. Number one to decrease the trial cost clinical trial cost of heart failure drug development through the patient stratification because our technology has two side. Number one is that we are able to go targeted patient specific cardiac tissues. We can develop a disease model outside and they can test the drugs. But the other side is that we are able to bring the right patient to the right drug to the clinical trials.

So smaller scale clinical trials precision more of a precision medicine. Yes. Okay. Right now one of the problems of investors shying away because clinical trials of heart failure is very very large 2500 people very costly and the failures at at the phase three. So once you have a failure in phase three, billions of dollars is like at risk. Nobody likes to be investing there. So they are expecting government investments coming in so that they can derisk and in the cancer area the incentives in precision medicine was significant while in the heart failure area it is almost very not equivalent.

So that means that we need not only the help from the investors to open the minds that there are new technologies that cost there's the clinical trials can be small trials and effective successful trials can be done because of the new technologies like what we have but also I think with the collaborative efforts there will be more incentives to create precision drugs and fund them. So your your technology is not only designed to potentially one day actually be a cure, but it's actually designed to be a precision diagnoser for heart failure. So the right drugs can be delivered or the right therapy can be Yes. Yes. uh because we can actually identify the diagnostic parameters of a specific patient population and then they can bring the drug from the disease model from the targeted population and when the drug is actually approved it is for the target population. So the treatment is very specific. So that is also a companion diagnostic area. So you are not only you know approving the drug

14:50 But it's a companion diagnostic side. So diagnostic companies as well as drug companies is going to be benefiting from partnering and because we are small we have one drug in in our library that we are working on a leap drug but the the technology can help many drugs development with collaboration. So where do you stand today like in terms of if you know getting something that would be is you go to get something clinically approved or is it designed to to work within the current research structure of a pharmaceutical company pathway like is it a standalone by itself or is it more like a strategic supporting tool for a company that's trying to develop a heart failure drug. Our platform can be support and can work with anybody like a CRO specific niche CRO or collaborative effort.

They can access the platform and develop their own drugs or bring smaller populations and we can help them to develop the protocol for which which population needs to be brought to the clinical trials for the success of the drugs that they have at hand. But or diagnostics but what we have is for heart failure preserved ejection fraction we call IVS 2011. We are trying to move that lead drug to the next stages of clinical trials and we are trying to generate a successful meaningful phase one data and from the biologically stratified patient population for that specific drug because we can stratify the population and when we do this one successfully the drugs will validate that how successful drugs can be many many drugs can be uh you know come out from a platform like what we have and so that others will not be shying away from developing precision medicine for heart failure and they will join the efforts of many many small scale drugs for

Subopuls because heart failure preserved ejection fraction has large subopuls. So but currently everybody takes one drug and right everybody goes to the same we are focusing on the group that has fibrosis on their heart and that is the reversal of fibrosis is our target for that population and that is why we are very targeted on where we are going for the clinical trials and that will be a drug candidate that pharmaceutical companies can come and collaborate and take on for for full commercialization and investors will continue working either with the sub libraries what we have other drugs or we can collaborate with helping others to develop their drugs. Well, that's quite a noble purpose. Sounds like a a big you know a big list of things to do. When do you have do you have time frame in terms of when all this might become viable or is that a topic you can discuss today? Yes, I think we are looking for the next 18 months for successfully raising the

17:45 Stage of the funding we need for the covering the cost of the phase one trials which is a smaller scale because we have human data already and that is if we are successful to show how small trials can be done that will open a floodgates for investors mindset and also as I mentioned that there is a mindset of an ecosystem system that needs to change because there's not much incentives, government incentives behind the development of the precision medicine drugs for heart failure. Maybe NIH is the one of the main sources but they are they don't have sufficient funds for everybody. They don't have sufficient funds to give every innovation coming out. And so what is happening again it goes to philanthropic groups that fund individuals, family funds that have the legacy that they want to come and contribute because they are already in the space. And so those individuals are very important to bring the new precision medicines for the next 10 years to the society and to prevent the

Burden of the taxpayers and to bring the a new solutions that is effective solutions to the patients and this is this is going to happen with the groups. So leadership will come through collaborative efforts. So not one company will be the queen or a king of the space like cancer field. There will be many many drugs will come. Everybody will win. There's enough money to make in this one. But I don't think expecting it government just will fund this. Currently incentives are very low compared to the cancer field. It has to change. It will come. That changes and that funding will come. I think Europe already is aware because they declare in Davos I believe the precision medicine and cardiac is one of the critical challenges for European countries and they have to find solutions that will be effective for cardiovascular diseases.

So there are leaderships looking into that but fundings even in Europe is way way behind to cancer area. So the funding's been a challenge then I guess is a friction point and um correct and I you know I know that I I talked to other founders and co-founders in the medtech and the pharmaceutical space and it's been a very challenging period to raise money and especially with a big problem like heart failure. Those are things where, you know, government assistance is definitely probably supported by a lot of folks. But it sounds like, was there some legislation that got passed for some new grant money too? I think just recently possibly in the legislature. Actually, I think SBI companies, NIH funding reopened, reauthorized.

20:39 And I would like to say that you know we are very grateful one of the companies and initially we got funding to do the prototype development and technology platform development through the university partnerships and without those funding investors doesn't come a very early stages and so the without those kind of funding the technologies like colossal and you know number one killer in the not only US around the world will not find a solution innovation. So we are grateful but at the same time I think there is a huge space where innovation efficiency and strategic partnerships still needs to come together and we cannot wait everything from governments. We cannot wait everything that they will be the solution and they will only be one funding but I think there is a room for larger scale of incentives from the government because oncology precision medicine only developed this far and this highly because of the government spending behind was proportionately significant other than heart failure is not much. So we have only one or two

Philanthropic funds trying to do work on this space and so I think everybody is competing for attention everybody is trying to get some you know funding and while this colossal problem taking lives daily and hospitalization is the big problem in the hospitals. So if 1% of that rehospization which is $300 billion cost paid back to the investors or through the structures I think more innovation will come and I think technology is already here. All we need to do to collaborate to bring the drugs together and I think we have enough smart people out there in it's very smart investors out there that pulling together the teams and making things happen in a collaborative manner shouldn't be a problem but I think it is still it is not a challenge that has been solved. So I am just one of the individuals and soldiers trying to make something happen. Well, and it's a it's a great purpose to have. I think at the end of the day, heart failure is a big

Problem. You're trying to solve that big problem, and we understand there's a long pathway to go with that as well with funding, large randomized clinical trials, all those things take time and money. And so getting as much support from a financial perspective is needed in order to solve these big problems. And so we we definitely have an appreciation for that. So moving forward, do you think there's is it a fiveyear window of time frame? Is it a 10y year? What do you think the the window is before technology like either yours or other technologies like yours gets to the market for us?

23:30 I think there's no reason for this will be not a 5 years window because technology has been already developed. There's no funding needed for technology. So that means that only thing we need to do is that to target the sub populations for heart failure with different drugs and not one company can have 500 drugs and that is why every company small companies will come up with their focus area of drug development but to uh our technology will be able to show that you can complete a phase one study with approximately 250 patient population.

This is a huge economical scale difference from the larger clinical trial to a smaller a very similar to cancer oncology approach. People who are in the field of oncology precision medicine development will know this economics and investment and the returns. But this is not happening in the heart failure. The moment few companies successfully start showing the drugs even those segments for a smaller population there is no reason for so many other drugs to do the same follow the pet and you know to target the other populations and then drugs will start coming out in time. So 5 years I think is very reasonable by knowing that stratification technology medical records AI integration and also the three-dimensional cardiammyioytes and disease models for heart failure patients is already developed and we only need to now focusing on specific diseases under the heart failure umbrella or cardiovascular right there needs to be more teams. So one team as I said one company can never be one. There will be pharma.

Pharmaceutical partners are critical. They need to be partnering opening more I think meetings for the smaller innovative companies and collaborate. Yeah. Well Ayla Annac and very good to have you today from Invivo Sciences co-founder and CEO. You can go to their website. I know that they have investor information there as well as a lot of the information on the technology. We wish you the very best. Thank you for joining me today and to discuss this huge problem that we definitely need our government and our resources to really begin to focus in on what heart failure does today. I I have experienced myself with the heart failure in in my family history. I understand the problem that it brings and it has mortality, it has quality of life and it has economic implications that you know definitely should be addressed. Thank you so much.

26:16 Very much appreciate your time today. We wish you the very very best of luck. Thank you for including and thank you for bringing the attention to this important matter. Thank you very much. That's a wrap on Zero Friction, the show built around one simple idea. Remove the barriers and the revenue will follow. If today's conversation was valuable, please subscribe and share it with somebody who needs to hear it. That's how we will grow this community. I'm Terry Coutsolioutsos, revenue architect powered by AI. Come find me at my website, myrevrx.com, and let's talk about what friction is costing you and your organization. Until next time, keep removing the barriers and keep the revenue flowing.