Episode 43: Pepper Landson- Co-Founder & CEO of Praetego

Join 30-year industry veteran Pepper Landson, Co-founder and CEO of  Praetego as she shares her inspiring journey that led her to tackle Alzheimer's and dementia through the innovative use of amadorins. Pepper's intriguing narrative not only highlights her commitment to the public health crisis surrounding these neurodegenerative diseases, but also the collateral damage they inflict on families and caregivers.

First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder. Episodes launch weekly on Tuesdays. To view the full transcript of this episode, click here.

Interested in being featured as a guest on First In Human? Please reach out to catie@vial.com.

🎧 Stay in the Loop!

For the latest news and updates, visit our website: https://vial.com

Follow us on social media for real-time insights:

Twitter: https://twitter.com/VialTrials

LinkedIn: https://www.linkedin.com/company/vialtrials

Chapters

• 0:07 Protego's Amadorans
• 13:30 Key Qualities for Biotech's Sustainable Growth

Transcript

Speaker 1: 0:07

You are listening to First In Human, where we interview industry leaders and investors to learn about their journey to in-human clinical trials presented by Vile, a tech-enabled CRO hosted by Simon Burns, CEO and co-founder, featuring special guest host Emma Moran, VP of C&S. In this episode, we sit down with Pepper Lansen, co-founder and CEO of Protector Portego. Learn more about Portego's innovative approach, using amadourns to tackle neurodegenerative diseases, and the importance of integrity, tenacity and compassion in the biotech industry.

Speaker 2: 0:47

I'm Emma Moran, VP of C&S at Vile, and I'm really excited to be joined today by Pepper Lansen. Pepper, would you like to briefly introduce yourself?

Speaker 3: 0:56

Thank you, Emma. My name is Pepper Lansen. I am a 30-year industry veteran. I co-founded a lead, a company called Protego, which is developing novel small molecules to change how we age, starting with Alzheimer's and dementia.

Speaker 2: 1:12

Thank you. So, Pepper, you've been involved in developing therapeutics for healthcare needs for a long time now. What initially drew you to a career in healthcare and pharmaceuticals?

Speaker 3: 1:23

I am by nature curious and I love problem-solving. These two drivers are welcome and in fact encouraged in our industry. But, like most folks who find themselves at a really opportune moment in time, it's never a linear process. So about 30 years ago I was fortunate enough to stumble into a job working with the US military to research HIV, and at that time there was nothing in treatment. It was just the beginning of clinical trials for what was then AZT, and of course everybody knows how that story turns out.

Speaker 3: 1:59

But the United States military and certainly a Department of Defense funding was in collaboration with the folks at NIAID. And that was when Tony was in charge and Debbie Burks was there, robert Redfield was there and this group of federal folk military, their medicine, their doctors, the scientists just wonderful people focused on solving a problem. They were working diligently to understand the disease and conduct clinical trials to study possible treatments. And working in that environment with these incredibly talented people was infectious. No one intended and after a few years of being able to have the pleasure of being around that type of folk, I was hooked and I've been in medical and clinical research ever since.

Speaker 2: 2:46

And, like Hugh Pepper, I've also worked in the Alzheimer's field for a long time, so I'm really interested to hear more about your research. Can you give us a glimpse into how Protego, innovative small molecules, the Amadorans, worked, safeguard against neurodegenerative diseases and share the fascinating research journey that brought them to life?

Speaker 3: 3:08

Again nonlinear stories, but the history of the Amadoran development spans 30 years, four generations of candidates and the third being Protego. The one constant is our CSO, dr Rajakalipa. He's a world-class chemist and he's also the inventor of the Amadorans. He identified the original molecule let's call it Gen 1. And its unique ability to inhibit a significant chemical reaction related to glucose metabolism. So you know, we all use glucose for energy and that's generally no big deal. However, as glucose is metabolized, it also loves to bind with long-acting proteins, lipids and bits of DNA. And these glycated units are targeted for non-ansomatic oxidation driven by redox metal ions.

Speaker 3: 3:57

And it's this event, simply known as glycoxidation, that can become harmful. The reaction produces highly reactive byproducts, pathogenic oxidative chemistries, to kind of put a big net around it. But it produces advanced glycation end products or AGEs. And when we're young or otherwise healthy, the body deals with the consequences of glycoxidation, or, more simply put, lipotoxicity. But as we age or have other comorbid conditions, those consequences start to add up. And what does this mean? It means oxidative stress and it means AGE accumulation. So what right? Why does this matter? It matters because these are two known drivers of neuroinflammation and protein aggregation, and this pathology encourages plaques and tangles in Alzheimer's disease.

Speaker 3: 4:50

So the amadorans, all four generations, demonstrate the ability to inhibit glycoxidation. Our mechanism transiently caps the redox metal ions that drive the reaction and as a result, the amadorans limit not one but at least three known promoters of neurodegeneration Redox metal ion toxicity, oxidative stress and AGE accumulation. And we have reason to believe that our candidates may also be protective of neuronal cells and by somehow protecting, maybe, the mitochondria and that's a new phase of research we're trying to further with these candidates. We've always known what they do outside of the cells, but now we have better technology to help us understand what they may be doing to benefit the inside of the cell. While the Gen 1 candidate did this by Gen 4, the lead candidate is two orders of magnitude more potent and what we've learned along the way and steadily refined, were features across each generation and we landed on the ideal for a chronic use drug in an aging population to treat age related diseases like neurodegeneration.

Speaker 2: 6:04

Wow, that's really fascinating. So Alzheimer's disease and related dementias are often referred to as a public health crisis. So how does Pertagos approach with these amadorians, uniquely position itself to address this crisis on a systemic level?

Speaker 3: 6:21

Let me set the table a bit for the scope of the problem. The collection of diseases that fall under the umbrella of dimension, for which Alzheimer's has the biggest footprint, is really truly a crisis, and I'm speaking as a caregiver to a mother without Alzheimer's, so I can honestly say that the collateral damage to family members, caregivers, is profound. This is not a disease that operates in a vacuum. It takes everything it can with it as it progresses. Children become the parents and parents become unrecognizable, and you have to have a wealth to afford supportive care or to place your loved ones in a home and then pray that that home will keep them safe. And that cost is out of reach for so many families and bed space and a suitable care facility is limited, so it will not keep up with the pace of the Alzheimer's epidemic, the dementia epidemics. It's obvious, with Pertagos candidates we aim to be an early intervention and to limit cognitive decline long before over Alzheimer's. And that's now possible because we have tools to identify folks at risk decades prior to having Frank cognitive decline, frank Alzheimer's symptoms, and so because we can measure it, we can go in sooner. So that makes it possible for a candidate like the Amadorans to be able to run a clinical program, run a series of clinical trials and ultimately have something we can measure, that the agency will say yeah, that's an approvable functional endpoint. It means clinical benefit. Now of course the challenge becomes how do you afford a trial? That's a little longer than you'd like it to be, but thankfully again, super smart people and statistics and some other really cutting edge clinical trial design techniques are coming of age that will help those of us who work in the chronic diseases of aging, like Alzheimer's, to slow things down and have trials we can afford to do. But back to your original question.

Speaker 3: 8:29

As I mentioned, we designed the Amadorans to have ideal features for a chronic use drug. They're oral right. Ivy infusions are great, but a lot of people can't access that level of care. We designed these candidates to have a wide margin of safety, so the room to play between the efficacious dose and the toxicity dose is really broad, and you want that in an aging population. We also designed them to be reasonable in terms of pricing. From the beginning, from the bench, we said these drugs have to be easy to make, they have to have good IP around them, but we don't want to use every most expensive ingredient in order to price these things out of the hands of most folks.

Speaker 3: 9:13

We have been thinking about this problem for a long time and I think with the current Gen 4 candidates, starting with PTG 630, we may have finally found the sweet spot. But the other thing that's super meaningful as a systemic answer to a systemic problem is our mechanism is beneficial to patients who have excess glucose, fueling this oxidative stress and AGE pathology pathway. So we all do it, but diabetics do it faster. That's now a known thing.

Speaker 3: 9:44

Diabetes is an extreme risk for Alzheimer's and dementia and our working hypothesis it's because of this glucose toxicity challenge. And if we can affect the beginning of that, then we can protect diabetics from having cognitive decline and we can protect everybody else from getting it too. So in my mind, with that I think, hopefully right Again, future forward thinking If we are right, then our drugs could benefit as many as one in 10. And if we're able to demonstrate sufficient safety profile when you talk about pre-diabetics being one in three in the United States, this is like a statin. This could actually protect people from a known undesirable outcome and be something they just take with the breakfast and get on with their lives.

Speaker 2: 10:36

Yeah, that would be absolutely amazing, wouldn't it? Yeah, really would. The biotech industry is continually evolving, so what emerging trends or technologies do you foresee as game changers in shaping the future of healthcare, clinical research and the broader biotech sector?

Speaker 3: 10:53

I'm a bit old school, I think, in some respects, because the more things change, the more they stay the same. We have AI and that's done some amazing things for our industry and for life in general. It's accelerated things like discovery. It's accelerated this concept of patient 20, which I think is really interesting. There was a team at Duke, which is right down the road from us, that did I will call it an artificial clinical trial, which I also thought was fascinating, and there's a paper around it and, of course, these things are super helpful.

Speaker 3: 11:24

But what I think would be most meaningful, when you're talking about the chronic diseases of aging, and specifically Alzheimer's and related dementia, is innovation in clinical trial design. The late stage trials, as I've already mentioned, they're wildly expensive and right now, the folks who can afford, the companies who can afford to do it, are big pharma and last I checked, pertego is not big pharma and so we have to have the mindset of partnering in order to have these big ambitions. But what I love hearing, I listened to a town hall by the ADDF earlier this week and Dr Philit, who's the head of ADDF, talks about how innovations and digital biomarkers are going to affect the way we do late stage trials, innovations in statistical design I've been reading when I can get my hands on around randomized start trial design which is really truly and potentially helpful if you want to demonstrate the value of a disease modifying drug versus a symptom management drug. Those are the kinds of drugs folks like Pertego are developing and some of the other companies in our space. So smarter clinical trial design using higher mathematics, statistical design, things like that.

Speaker 3: 12:42

It's not necessarily the fancy buzz at AI, it's just recognizing we have to be creative and do it better. These are little iterative steps that don't discount the need for man years for safety. Right, we cannot cut corners on confirming these drugs or will tolerate it, because these patients are already compromised, they're older, they have other things going on. So as long as we recognize that there are ways to be creative and progressive without sacrificing good science, integrity in our research, integrity in our data and, of course, honoring the patients who give us their time and everything else, we can do it better. We just have to do it better.

Speaker 2: 13:28

Absolutely Pepper. In your opinion, what key qualities are essential for a biotech company's sustainable growth and impact in the long term, and how do you ensure that Pertego embodies these qualities?

Speaker 3: 13:42

It's a really powerful question and I think it transcends biotech integrity integrity of process, integrity of people, even integrity of the goal. The thing you're trying to solve are your company's values in alignment with the way you are Developing your candidate. That really matters to me, as I had mentioned offline you know, in addition to 30 years in industry, I'm also a trained executive coach and that has been one of the greatest resources I have as a startup CEO is recognizing the values of the company need to be considered and In the context of how we move forward with developing drugs right. So, as I mentioned, dr Khalifa is a world-class chemist. The integrity of the process by which he considers our candidates and develops our candidate it's top drawer when he's had a huge influence on the way I approach things. So integrity, tenacity these are big, hairy problems that are going to take some pretty strong people who are relentless in their pursuit of an answer. Right, because if we wilt at the first sign of trouble, we won't get very far. Perseverance, of course, as a feature.

Speaker 3: 14:57

Compassion why are we doing what we do? Because we want to help people and, as a CEO, one of the things I ask anybody we consider hiring, or even any vendor we consider working with this. Do you have a wellness plan for you as a person? Because if we don't take care of ourselves while we're doing these hard things, we'll burn ourselves out. That doesn't serve the mission, and so self-compassion compassion for the process, for each other I think is meaningful and certainly focus right. There's lots of shiny things to get distracted by. We're all guilty of it, but maintaining certainty and integrity of the mission, I think is also really key. But most of all, oddly enough, I think we need to remember that the best form of health care is human connection and kindness, right Long before we ever made drugs or needed drugs. Being in community, creating community, being there for each other I think that transcends all biotech and I have an active practice to make sure we do that on a routine basis as a company.

Speaker 2: 16:07

So with all your experience, pepper, have you got any words of wisdom for young people starting a career in farm, seach calls and biotech nowadays?

Speaker 3: 16:16

Yes, actually. First let me speak as a caregiver to an Alzheimer's patient and I'm an APOE for a carrier too and so what we've learned as an industry, as a community of scientists and clinicians, is that we can take Substantial action now, and especially when you know those who are younger to practice Good habits that will be brain protective, health protective, right. And there's the obvious stuff eat well, exercise frequently. And the less obvious ones make time To have fun, make time for the people you love being around to inspire you, who remind you to laugh, human contact, and especially Positive human contact, and I mean like the kind that makes you laugh until you blow milk bubbles out your nose. That's its own form of medicine, right? And so all work and no play is not a recipe for sustainability as an individual or even a company.

Speaker 3: 17:17

So, speaking as a health care advocate, not just a ceo, I have a practice that I have to give myself in order to do my job, and I highly encourage that In the community that I'm really active in here in rtp of other ceos, of life science companies, we all have to take care of ourselves in order to do our jobs, because these are not easy jobs, but in terms of anybody considering a job in biotech.

Speaker 3: 17:44

I love the fact that biotech has one of the lowest pay disparities between the sexes right, so women have near-car for their salaries and I think that's super important. I've had the pleasure of traveling the world working in research on somebody else's dime without having to join the military, so I thought that was pretty cool too. And, at the end of the day, find something that really lights you up and then work super hard at it and recognize it's the long game right. Quick solutions do not work. You recognize. In the grand scheme of things, that's okay because the setbacks teaches things and if you really love the work, it's a great lifetime career and you really will have impact on the quality of life of people. You'll never meet as well as the people you know and love.

Speaker 2: 18:39

Very wise words. Thanks so much for joining me today.

Speaker 3: 18:43

My pleasure. Thank you, Emma.

Speaker 1: 18:52

Thanks for listening. Be sure to follow us on Spotify, apple, youtube and Google.