Speaker 1:

From the New York Stock Exchange at the corner of Wall and Broad Streets in New York City, welcome Inside the ICE House. Our podcast from Intercontinental Exchange is your go-to for the latest on markets, leadership, vision, and business.

For over 230 years, the NYSE has been the beating heart of global growth. Each week we bring you inspiring stories of innovators, job creators, and the movers and shakers of capitalism here at the NYSE and ICEs exchanges around the world. Now let's go Inside the ICE House. Here's your host, Lance Glinn.

Lance Glinn:

Nearly half of all pills we take today trace their origins back to molecules hidden deep within nature's vast and largely unexplored chemical library.

Despite this incredible potential, the complexity of natural mixtures has turned most of these compounds into scientific mysteries. That's because isolating individual molecules, unraveling their intricate structures, and fully understanding their biological effects require an immense investment of time, specialized expertise, and costly resources, challenges that have kept much of nature's pharmacy out of reach for modern medicine.

Enveda is unlocking nature's hidden potential by leveraging AI to unravel the intricate chemistry of plants and other natural resources. Through this deep exploration of complex natural mixtures, the company uncovers molecules that traditional drug discovery methods have long overlooked.

Founded in 2019 by our next guest on the Biotech Series, Viswa Colluru, Enveda is pioneering a healthier future, empowering scientists to tap into the vast unexplored code of life's chemistry. Viswa, thanks so much for joining us Inside the ICE House.

Viswa Colluru:

Thank you so much for having me, Lance.

Lance Glinn:

So let's start by just laying the foundation for listeners who may be unfamiliar with your work, what is Enveda Biosciences and what was the core problem in drug discovery or modern medicine that you set out to solve when founding the company in 2019?

Viswa Colluru:

Enveda was born out of a really simple realization. It's that the core problem in the industry is things that work in the lab don't work in people. Right? The industry spends years and millions of dollars coming up with a molecule, which is usually the hypothesis that everybody wants to test, put it in clinical trials only to have it work somewhere between 7 and 14% of the time, depending on the disease you're testing in.

And when I realized that actually embarrassingly long into my career in the biomedical sciences, I asked not what everybody else was doing, but maybe what was remaining undone. And I looked around and I saw that everybody's focus was on biology, was on understanding disease mechanisms better, but there was very little focus on understanding what the best chemistry was for medicines.

And this had two really interesting points of allure for me. The first one was historically the most successful medicines of the industry, in fact medicines that birthed the industry, didn't come from a deep understanding of disease mechanisms or combi chem or any of these modern technologies we associate with biotech, they just came from humans observing other humans sampling their environment, right? That's how we got morphine and aspirin, the first two drugs to ever be put in a bottle and sold, but also artemisinin and quinine, things that have touched billions of lives and continue to touch billions of lives and won Nobel Prizes.

The second point of allure was, okay, even if these historical acts of observation don't pan out in rigorous modern trials, very rarely do you find an idea that is untapped while being validated.

And what I mean by that is there's only about 3 or 400,000 compounds from living systems that have ever been discovered by scientists, but they gave us nearly half of all FDA-approved small molecule medicines.

So the fact that we are at this intersection of being extremely validated as a source of success while being largely unknown, today we estimate somewhere between 90 and 99% of the world's chemistry is hitherto unknown, is a very unique point. And for me, those things made it very exciting to build a company that is able to bring the world's most powerful chemical library to bear and put it in the hands of drug hunters.

Lance Glinn:

Yeah. So I was doing research as I was preparing for our discussion. I saw Enveda follows sort of this belief of nature being the world's most prolific and sophisticated chemist, and that, as you just said, we've really only scratched the surface of what's possible when it comes to these compounds.

How is Enveda using technology to uncover new therapeutics from these natural products that historically may have been overlooked by biotech and pharmaceutical?

Viswa Colluru:

Yeah, that's a really good question. In fact, that is the question that comes immediately after the set of realizations I laid out in my last answer.

If historically this has been highly successful, and the idea is also deeply intuitive, right? Because living systems create molecules that are useful for living systems, then why did the industry move away from it? Why has the collective scientific enterprise only given us 300,000 compounds?

And the short answer is that we didn't invent technology that allows us to take any sample and answer two really simple questions. What are the molecules in the sample, and what do they do? Right?

In other words, chemistry never had its next-generation sequencing moment. Today you can take any natural sample, you can amplify the genetic material, and you can ask what is the sequence of nucleotides? In other words, what are the genes? And then by comparing them to other sequences, ask what they might do.

But there really isn't an equivalent for being able to crack the chemical code of a sample. And so the tech that we do, the tech that we use at Enveda essentially allows us to answer those two questions. And we use a combination of a technology called tandem mass spectrometry, and we use machine learning algorithms to help us understand tandem mass spectrometry such that we can annotate chemical structures at scale without needing to isolate individual compounds. And that's maybe the foundational one and then there's a whole host of other things we do to answer the second question.

Lance Glinn:

So you mentioned machine learning, I want to pivot the conversation now to AI, is a central tool in your drug discovery process and becoming more and more of a central tool in the drug discovery process as a whole throughout the industry.

Viswa Colluru:

Yep.

Lance Glinn:

Break down just for our listeners how you are using it to really analyze these natural compounds and what role AI plays just overall in your processes?

Viswa Colluru:

Yeah. AI is, at the end of the day, a set of technologies that allow us to recognize and generate patterns, and biology and life is full of them.

So what we use AI for is to be able to understand the grammar of life's chemistry that is present in the fingerprints generated by the process of mass spectrometry.

Mass spectrometry, as the name suggests, is measurement of mass. And to explain it very simply, it is a set of instruments that allows you to take a sample and align them such that one by one they go into a detector that measures mass. And then that same detector has hardware that allows it to essentially break apart that mass by accelerating it through neutral gas, such that each molecule has an intrinsic fingerprint in how it breaks apart.

Now, historically, these fingerprints were used this just the same way as humans use fingerprint databases. We look for other molecules that have previously been discovered, essentially facial matches to the fingerprint.

What AI is allowing us to do is turn the tables on that, because that old method allows you to only rediscover known chemistry. Instead, our technologies allow us to read those fingerprints and directly predict what the chemical structure may be.

Lance Glinn:

So AI has brought speed and scale to early-stage drug discovery, but there's still, I think, the question of the meaningful results that it could produce, right? How impactful, at least early on, and I know AI has been around for decades, but this new generation of AI, the gen AI, the sort of post-ChatGPT AI, what are the meaningful results that it can produce?

So just from your perspective, what's the most realistic near-term impact AI can have across full drug development pipelines from discovery to clinical trials and eventually to patients that need it?

Viswa Colluru:

Yeah. From where we live and from where we look, AI is the cornerstone of what we do. Enveda would not be able to unlock completely new chemistry that has been out of the reach of the industry and honed by evolution for billions of years without generative AI.

Lance Glinn:

Sure.

Viswa Colluru:

And the ability to unlock that chemistry in terms of very real progress, to answer your question on discovery, translation and clinical, this technology has allowed us to create multiple new medicines about four times faster than the industry average and move them into clinical trials. We have our first program that just finished Phase 1 trials, and we have three more that we'll be moving into the clinic over the next six months.

And each of these, it's not just about maybe the speed and scale, but each of these medicines, we believe, offers a completely different, unique, and superior value proposition to patients.

For example, our lead program reimagines what's possible with an inflammation drug. Right now if you are a patient that suffers from asthma or eczema, you really have two choices. You can take oral medicines that are either steroids or kinase inhibitors that come with either long-term limitations or serious toxicity concerns, or you can take injectables in the form of biologics.

Our drug, ENV-294, which has only been possible because of our ability to deconvolute new chemistry and turn it into a first-in-class drug, essentially takes the best of both worlds. It's oral and safe while being as effective as the most powerful anti-inflammatories we have today.

Lance Glinn:

We're going to talk more about ENV-294 in just a little bit, but before we do, if you look at AI and you say to yourself, "Okay, it can lower the costs, then potentially shorten the timeline of bringing a drug to market, it has the potential to, I think, fundamentally change who gets access to medicine and how quickly they do get access to such medicine," do you believe AI can help create a more equitable and efficient future for drug development? And how does Enveda's work contribute to that broader mission?

Viswa Colluru:

I think you laid out all the pieces in your question. If AI does in fact allow us to create better medicines faster, then the overall cost of drug discovery and the reach of drug discovery, today 90-plus recognized diseases don't have an approved medicine, should democratize. But I think maybe the far more important question is how will AI do that?

And in my view, AI will do that not by taking the existing steps in the playbook of drug discovery, and making each one of those steps more efficient, because I think there's emerging evidence to suggest that the limitation is not in our ability to do those steps or in the cost of those steps, but really at the culmination of all of those steps, does the molecule work? Right?

So AI, in my view, will actually bring about a transformation of drug discovery by allowing us to reimagine and rewrite completely new playbooks. And such re-imagination I think will involve a component of us being able to appreciate and harness the complexity of biology and not rely on a paradigm of a single protein and a single molecule against that protein.

Already, as far as Enveda's concerned, our ability to create medicines four times faster and about 1/10 of the cost allows us to make more medicines and go after more diseases where there are patients waiting for better options.

And also from a purely financial perspective, we have turned early-stage drug discovery into a risk-adjusted NPV-positive endeavor. Not to throw financial jargon at you, but essentially we've made it where it's a worthwhile investment, despite the fact that only a fraction of them may end up working in the clinic.

Lance Glinn:

Hey, we are here at the New York Stock Exchange. Financial jargon just sometimes works its way into all these different conversations even when not planned, but you brought it up in a previous answer, ENV-294, and I want to highlight that as a recent obviously achievement for Enveda.

The company a few months ago announced successful completion of its Phase 1 clinical trial on the drug, atopic dermatitis, asthma, inflammatory issues. These things affect millions of people worldwide, yet many struggle to find the treatments that are both effective and, I think most importantly, manageable as well.

So how do you see ENV-294 go deeper into it? How do you see it potentially changing the experience of patients living with these various conditions?

Viswa Colluru:

Yes. The key principle at the company for us is to always start with the patient in mind. And when we looked at the market, we realized that a big gap that existed was a safe option that was also convenient in the form of an oral medicine.

When we talked to patients, we saw that there was a large section of the populace that just did not want to get on a regimen of injections for what they considered a chronic condition, rightfully so. We also realized that for atopic dermatitis especially, it is a disease that for a lot of people can start in childhood.

And so safety, and again, convenience in the form of a pill versus a shot, becomes a very big concern. And so we wanted to make a medicine and position a medicine such that it has the safety that is needed to bring prescription-level care to millions of patients. And we are extremely excited by the fact that in what seems to be an extremely large market, we're maybe one of a couple of drug companies with the profile set to achieve that.

Importantly, I think the existing medications, even though they're effective and are blockbusters like DUPIXENT, they still leave a large proportion of patients non-responsive either at the three-month mark or the one-year mark. And early signs for our biology suggests that we should have a much broader and deeper remission profile.

So ideally, you get diagnosed with eczema, you try some over-the-counter treatments or some steroids to bring around the flares, but you never even have to advance to these advanced therapies. You can stay on Enveda's drug and achieve lasting remission while not increasing the risk of unintended side effects.

Lance Glinn:

Well, I don't want to congratulate you too early, but yeah, fingers crossed-

Viswa Colluru:

Fingers crossed.

Lance Glinn:

... and all seems to be pointing in the right direction. So the completion of these Phase 1a trials and the launch of Phase 1b marks a major milestone for the company.

What does this success mean to you and the team not just in terms of this clinical progress that's being made, but in just validating the entire platform and approach that you've been building?

Viswa Colluru:

I think I would be hard-pressed to find words to describe how much it means to us. We recently tested, for example, a version of this drug, another molecule from the series, in a study with pet dogs.

And the reason we did that is pet dogs tend to be a really incredible model for human eczema. And the last three first-in-class or novel mechanistic drugs that got approved in human eczema first worked in dogs.

And the reason I bring that up is we can't wait to have real impact on real lives. And those are not just numbers. Each individual life matters.

And so the first guest in our boardroom now will be a dog named Bailey whose life we meaningfully improved, and we got a wonderful letter from his owner, Jeff, that also now lies in a frame in our boardroom. And we can't wait to frame maybe a photo of our first patient as well.

And we think it's just the beginning. Our goal over the next decade is to become a household name, create medicines that matter, and touch hundreds of millions of lives.

Lance Glinn:

So Viswa, as we begin to really wrap up our conversation, culture and team become critical as companies grow quickly. Just how are you thinking about building and sustaining the right culture at Enveda to support innovation and execution at scale?

Viswa Colluru:

Culture I think has been said eat strategy for breakfast. And I always thought maybe that was a little bit of hyperbole until I took on the mantle as founder and CEO and realized that was probably an understatement, if anything.

And however, it's one of the things that we're most proud of at the company. We've won numerous awards, most recently Newsweek's Top 100 Global Most Loved Workplaces. We have an NPS in the eighties in the company across all of our offices globally. And the key piece for us there is to hire really smart people and imagine ourselves in their shoes every day.

My philosophy around building a culture is not some magic formula, but really realizing the fact that every human intrinsically is wired for impact.

And so our approach is to imagine ourselves in the shoes of smart people and maniacally remove every obstacle that would demotivate them, right? We sat on the African savanna hundreds of thousands of years ago and yearned for the stars, and here we are doing it, and it didn't require someone to motivate us.

Lance Glinn:

Absolutely.

Viswa Colluru:

So that's the philosophy we take.

Lance Glinn:

So, Viswa, as we wrap up our conversation, what does success overall look like for you, not just in terms of FDA approvals or trial data like we discussed with the ENV-294, but in terms of the real-world change that you hope Enveda creates?

Viswa Colluru:

I think that success for us will be Enveda becoming one of the most globally-loved companies, which is actually somewhat unique for a pharma company.

If you imagine, and you look around today, pharma companies tend to create brands around drugs rather than the companies themselves. And I have to imagine that's because brands around companies are difficult to navigate and so on. But if you create an incredible workplace, fantastic products, get them to patients that need them, you should be a household name that's loved.

And for us, those ambitions underlie all of the things you mentioned, multiple FDA approvals, commercial stage ambitions, becoming a company that directly delivers products to hundreds of millions of people. But at the end of the day, at the turn of the century I hope, one, Enveda's still around, and two, it has the same brand recognition as Apple.

Lance Glinn:

Well, Viswa, I wish you luck in the continuing clinical trials, and I thank you very much for joining us Inside the ICE House.

Viswa Colluru:

Thank you so much for having me again.

Speaker 1:

That's our conversation for this week. Remember to rate, review, and subscribe wherever you listen, and follow us on X @ICEHousePodcast. From the New York Stock Exchange, we'll talk to you again next week Inside the ICE House.

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