Become a Creator today!Start creating today - Share your story with the world!
Start for free
00:00:00
00:00:01
Ep. 33 How Lytix Biopharma Reimagined Host-Defense Peptides as Oncolytic Molecules for Immunotherapy
0 Plays2 seconds ago
In this episode of Spark Time!, we speak with Øystein Rekdal, co-founder and CEO of Lytix Biopharma, about how the company reimagined host-defense peptides as a new class of oncolytic molecules for cancer immunotherapy.
Øystein shares the full arc of Lytix’s development, from an academic discovery in Norway to a clinical-stage platform built around locally administered oncolytic molecules designed to activate the immune system where standard treatments fall short. We explore how Lytix isolated and engineered naturally occurring peptides into drug candidates with clinical momentum, and why this approach differs fundamentally from both traditional cytotoxic agents and oncolytic viruses.
The conversation dives into how Lytix’s lead program induces immunogenic cell death, exposes tumor antigens, and initiates a broad immune response that extends beyond the treated lesion. We also discuss the company’s strategic focus on combination and neo-adjuvant settings, its rationale for intratumoral delivery, and how this platform is positioned to address non-responsive solid tumors.
A thoughtful discussion for biotech leaders, investors, and partners interested in differentiated immunotherapy platforms and the strategic decisions required to translate novel biology into real clinical relevance.
Recommended
Transcript
Introduction to Sparktime
00:00:00
Speaker
Welcome to Sparktime, where biotech's thought leaders, investors, CEOs, and industry experts break down the evolving story of life sciences. Hosted by Danny Stoltzfus and Will Riedel, two scientists and strategic communicators, we dive deep into how biotech leaders can shape the narrative, win investor confidence, and communicate breakthrough science in ways that truly resonate.
Emerging Trends in Biotech
00:00:21
Speaker
From emerging trends and cutting-edge technologies to what investors and partners really want to hear, we go beyond the usual echo chamber, bringing you fresh insights, unexpected perspectives, and the strategies that set biotech's top players apart.
00:00:34
Speaker
If you want to sharpen your corporate messaging, decode industry shifts, hear from voices shaping the future of biotech, and get inspired, then you're in the right place. Let's get into it.
Dr. Ersteen Rechdal's Biotech Journey
00:00:46
Speaker
Today, our guest is Dr. Ersteen Rechdal, co-founder and CEO of Lytix Biopharma. He's been driving this science from its earliest days through the hurdles that usually stop natural product programs in their tracks and into a neoadjuvant clinical strategy that is showing meaningful clinical outcomes for patients. Ersteen has seen every stage of this journey and has built Lytix into a company with a genuinely distinct position in immuno-oncology that has managed to do something almost no one pulls off in oncology.
00:01:15
Speaker
Lytx
The Science Behind Rexatematide
00:01:16
Speaker
Biopharma took a naturally occurring peptide, isolated it, engineered it, and turned it into a drug candidate with real clinical momentum. Their lead asset, rexatematide, is designed to kill cancer and trigger a durable systemic immune response, making the immune system finally see the tumor.
00:01:33
Speaker
By injecting it directly into the tumor, rexatematide disrupts tumor cell membranes, triggers immunogenic cell death, and activates a broad T cell response. In other words, it turns a cold tumor hot and creates the conditions where checkpoint inhibitors can be much more effective. So, Ersteen, welcome to Sparktime. How are you today?
00:01:52
Speaker
Thank you, and great to be here. Thank you for the invitation. Awesome. Yeah, so Oisteen, I wanted to start the conversation around where we began with roxotematide because my understanding is that it's a naturally derived product that's actually been able to make that leap into a commercially viable drug. and the reason I find this interesting is, you know, my background was many, many years ago was trying to do the exact same thing with natural products. And it's extremely challenging to to do that. So walk us through those early days. How did you isolate it? How did you understand its potential? And how did you start shaping it into a drug candidate that we have today?
00:02:33
Speaker
so thank you for giving me that opportunity ti to go. Back in the old days. So it actually began at the University of Tromsø, the northernmost university in the world, in fact, located in northern part of Norway.
00:02:49
Speaker
I was doing my PhD then ah while I also was setting up a small peptide production facility for different research groups. And one one day a
Patenting Breakthroughs
00:02:59
Speaker
microbiology professor approached me and asked if I could synthesize a short fragment of a protein that is found in high concentration in raw calf milk.
00:03:10
Speaker
And this peptide was found to have 10 times stronger antimicrobial activity than the original protein. Later, when I discovered that the parent protein also had the anti-cancer effects, I asked myself, could this peptide fragment also be more potent towards cancer?
00:03:29
Speaker
Another PhD student and I tested the peptide fragment and the parent protein in a mouse tumor model. And to a big surprise, the peptide fragment did not only work better than the parent protein, it actually cured the animals from cancer.
00:03:45
Speaker
So that moment became became the starting point for everything that followed. And from there, the university and hospital joined at Intromse, a larger effort to understanding the biology as well as the chemistry behind these effects.
00:04:00
Speaker
And by apply applying quite advanced medicinal chemistry technologies, we were able to design shorter and even more effective molecules. And that was really the beginning of what ultimately became ruxotermitide.
00:04:16
Speaker
First of all, my PhD was not nearly as exciting as yours was by the sounds of it because I didn't do anything that interesting and make that big of a discovery. So it sounds like that initial mouse experiment it was kind of when you went, aha, we have something that that's really working here. is is that accurate? yeah Yes, absolutely. Because when we have cured ah and the the animals from cancer, we had the possibility to reestablish, try to reestablish the tumors in the mice, which was I think was a very smart move that time, retrospectively.
00:04:51
Speaker
So reestablish tumors in mice that already had been cured with the peptide fragment. And we we expect expected that the tumors may grow again, but it was shown that they did not.
00:05:04
Speaker
it seemed It seemed, in fact, that the peptide fragment had evoked a prolonged response in the animals that did not allow the cancer to develop again. So that was when we realized we weren't just killing cancer cells. We were
Rexatematide's Unique Mechanism
00:05:19
Speaker
triggering a protective immune response that resulted in a sort of a therapeutic vaccine effect.
00:05:25
Speaker
And at that point, my colleague and I had to make a big decision. Should we publish these exciting results immediately in a high-impact journal or keep it confidential and file patents and see if we could bring this all the way to the patient? And I'm i' very glad that we choose the latter today.
00:05:44
Speaker
I would love to hear more about what ruxotematide actually does inside of the tumor microenvironment. How does it have that effect? Yeah, so ruxotematide is given directly into the patient's tumors, where it works, in fact, in two different ways.
00:05:59
Speaker
First of all, it rapidly kills cancer cells in a way that exposes the tumor's unique mutation to the immune system. Second, it activates immune cells locally. So they start attack attacking cancer cells that have not been killed directly by ruxotamitide.
00:06:18
Speaker
The result of this is a tumor that becomes infiltrated with active immune cells, essentially converting a cold, non-inflamed tumor into a hot inflamed tumor.
00:06:30
Speaker
In addition to this local effect on the tumor microenvironment, the immune cells start searching for cancer cells elsewhere in the body to fight the whole cancer disease. So a very unique and exciting and mechanism of action by Ruxotermatide.
00:06:47
Speaker
Yeah, I mean, it it sounds like the the holy grail that everyone's looking for in my understanding of, you know, sort of prolonged anti-cancer activity, right, is to actually truly engage the systemic immunity that you're describing.
00:07:02
Speaker
Yes, exactly. So when you talk about this to investors, like it almost, I mean, do they have the, wow, this sounds too good to be true reaction? Or what what is it that they misunderstand about this class of molecules? Because I i think this, ah you know, ruxotematide is probably pretty unique in the way that it operates. And maybe they're not so familiar with these molecules. yeah You know, we we so we understood that this had something different from all other classes of immunotherapy. And and we saw tumor model after tumor model. We were able to cure and we were able to induce this protection. So we knew we had something very unique. But of course, when we were talking and telling about this, there were not so many who believed this could really be possible.
00:07:51
Speaker
translated into human settings. So I think there were two things often misunderstood. First of all, as you may know, and maybe a lot of you other people listening here, is that who there are some similar terms out there, like oncolytic viruses. Yes. and call And because we call them oncolytic molecules, some investors assumed they were related to these oncolytic viruses or we were had produced fragments of all linked viruses. So that was quite frustrating that they missed it. But the oncolytic molecules are not. This is an entirely new class, small chemically engineered peptides and molecules which behave different from the oncolytic viral therapies.
00:08:35
Speaker
Second, some think they act only as cytotoxic agents and that they kill cancer cells in a similar way as chemotherapy do. But in reality, our drug candidates kill cancer cells in a way that train the immune system to recognize and attack the cancer disease throughout the body, which is very different different from...
00:08:58
Speaker
conventional chemotherapy and cytotoxic agents. And this immune activations is just as important as the direct tumor lysis and killing as we see. Yeah, can you explain a little more that the nature of what happens when the tumor cells
Combining Therapies for Better Outcomes
00:09:16
Speaker
die? So I guess what I'm asking is tell us a little more about immunogenic cell death and how that primes the the immune response that you're seeing.
00:09:25
Speaker
Yeah, so immunogenic cell death is ah a well-known term in the field of immunotherapy that there are certain compounds that kill cancer cells in a way that the immune system is activated in a certain way, whereas most of the chemotherapy and killing less cytotoxic agents kill cancer cells in a more silent way. They are killed and they are removed by some immune cells in the body.
00:09:52
Speaker
but Not only do we induce this immogenic cell that that you kill the cancer cells in a way that the immune system will get activated, but we do it in a very unique way. And I think the most unique of our drug compared to chemotherapy is that we really open up the tumor cell. So the tumor mutation, the mutated proteins get exposed and you in a way train the immune system to see
00:10:22
Speaker
see this mutation and look for cancer cells with similar mutations throughout the body. so this So it's both a unique way of killing the cancer cell, a unique way of immunogenic cell death,
00:10:39
Speaker
ah different from many other immunogenic cell death inducer. And in addition, we both see an effect of that is that the immune system is activated.
00:10:49
Speaker
But also we see additional pathway for immune cell activation, which makes eruxotermatide even more unique and more powerful. So I'm curious about combination effects. How do how do you envision rexatematide being used in combination with standard of of care agents? and And how do you see that transforming or or changing how patients are treated right now? Yeah, so we are focusing on on combination therapies because I believe a metastatic cancer is very...
00:11:21
Speaker
difficult to treat with one type of therapy. And we have done some combination studies with the ruxotermatide and approved chemo immunotherapy like yeah immune checkpoint inhibitors and specifically pembrolizumab and anti-PD-1 inhibitor.
00:11:40
Speaker
so hold us these to ah modalities complement each other. So checkpoint inhibitors like pembolizumab, they remove the brakes from the immune system.
00:11:51
Speaker
But that only help if there are immune cells present in the tumor to begin with that are active. In many patients, the tumor is simply too immune cold. There are low number of immune cells or they are not activated. So removing a break in the immune system doesn't help.
00:12:10
Speaker
So roxotembitide does a different part of the job of fighting cancer. It starts the engine in a way. It activates immune cells and attracts them into the tumors. And when you at the same time remove the breaks with Pembolizumab, the activated immune cells can work over time to finalize the job of eliminating cancer cells cells. So this is why combination is so compelling for us. Our drug activates the immune responses. Pembolizumab unleashes the breaks, making sure that these immune cells can work over time and and hinder that the immune system downregulated. So the drug works locally. I know you mentioned intratumoral injection, um but of course it produces systemic effects like you're you're describing. So what does that mean for patients with multiple lesions? If it's injected at one tumor, does that mean that it it has an effect um at at multiple tumor sites? Do other tumors become hot instead of cold now? Yeah, so that's a ah very good question, an important question. So Ruxotematide has this act local, think global effect.
00:13:21
Speaker
So when we inject Ruxotematide into one accessible tumor, that tumor becomes a sort of a training center for the patient's immune system. So once the immune cells locally learn what they should look for, they travel throughout the body and attack tumors and kill tumor cells located elsewhere.
00:13:42
Speaker
And we have seen distant untreated lesions shrink or disappear completely because the immune system has been activated locally at another location in the body and then attack cancer cells throughout the body.
Patient Success Stories
00:13:56
Speaker
So this is a very unique way again of killing locally, activating immune system locally, and we see this um and yeah very promising effect in the systemic way.
00:14:08
Speaker
I love that. act Act locally, think globally like ah like a good citizen. yeah ex ah Exactly. is I totally totally agree. yeah So in terms of now thinking about how this could potentially impact patients, what is the practical way that priming their immune system before they have surgery or another line of therapy like pembrolizumab, how does that translate for them? Does it save them time? Does it potentially extend their survival? like How do you think about the the impact on patients?
00:14:43
Speaker
So again, a very ah relevant questions in current immunotherapy, how this is moving. So so absolutely important to... to think think about. So the rationale behind this strategy is that the immune system in patients is strongest early in the disease.
00:15:04
Speaker
so So if we can activate the patient's immune system before surgery, the patient can develop a stronger and more durable immune response than giving the treatment at the later stage.
00:15:15
Speaker
For example, after several lines of therapies where the immune system and the patients also so start to get exhausted. so So giving immunotherapy early in the disease may reduce the chance of recurrence after the surgery, and and also and also but also eliminate any micrometastasis that is not being diagnosed or and is not possible to remove either surgery, for example, in in in ah in the lymph nodes close to the tumor. So being ah being able to help the patients early in their disease can potentially spare the patient for months of ineffective treatments later.
00:15:53
Speaker
And some of these later stage therapy may also give ah more severe side effects to the patients. so So in many ways, neo-djuvant immunotherapy, meaning treating before surgery, is giving the immune system its best possible chances but to succeed in combat the cancer disease. This is how I see it.
00:16:13
Speaker
come early in really use the immune system when it's at its strongest to really eradicate the cancer at the early stage. And and you can save a lot of suffering for for the patients that may don't have to go through a number of suboptimal therapies with even also some so severe side effects.
00:16:35
Speaker
Yeah, that's a ah really interesting way to think about it. And my brain, when you talked about micro lesions in lymph nodes, that made me think of someone I i actually know quite well who went through this process where they had their initial tumor removed, but then they also had all of their a large amount of lymph nodes removed to make sure that the disease didn't spread. But of course, that has side effects of things like lymphedema, which I know a number of cancer patients deal with. So it sounds like Exactly. Yeah, like you could actually prevent a lot of the non-cancerous ah side effects like something like lymphedema, which, you know, there is no good treatment or cure for. So that's really cool. Absolutely, because, you know, you can reduce cancer ah in size, but it's really about the ability to to prevent recurrence and relapse. And that can happen from this micrometastasis that you cannot prevent.
00:17:32
Speaker
maybe not even see or or locate, identify, but also not, and therefore difficult to treat. But here you have an immune system that can search for these neighboring locations of, of and as you say, in in the lymph nodes.
00:17:46
Speaker
Yeah, that's really powerful. So do you have any patient stories that you can share about, you know, someone that's received your treatment and how that altered the change of their, the course of their disease?
00:17:59
Speaker
So we have, of course, several examples where our treatment has had big um impact on the patients. cancer and improve their quality of life. ah But when you ask that, maybe there is one patient story that has been very inspiring for me, at least, that I could share. And in fact, this case story has even been published because it's little bit different case story than than what we are talking about with the combination.
00:18:28
Speaker
This was early days when we we tested the ruxotermetide alone and not in any combination. And we we were testing in in a lot of different cancer types ah or ah patients with different solid tumor types.
00:18:42
Speaker
And there was this young, relative young woman that had a very aggressive tumor called Desmoid cancer. cancer. ah It was deep in her left chest wall.
00:18:54
Speaker
that had annaity it had come It had become very large, approximately eight centimeters. So a very large tumor. And this tumor, of course, caused a lot of problems and challenges for the patient. It caused constant neuropathic pain.
00:19:11
Speaker
and And she had to use quite strong painkillers. But even despite so despite receiving the strong pain relievers, she woke up approximately 10 times every night.
00:19:23
Speaker
So huge problem for her life quality. And she also had ah lost her arm function on the left side. They were considered surgery, which required massive resection and wasn't recommended. She she was also too young for radiotherapy due to the long-term risk of the secondary cancers.
00:19:44
Speaker
ah But because she had responded previously to one type of immune therapy, that she unfortunately had to stop due to some side reaction. Her doctor thought intratumorally administration of ruxotermatide might work, and and and her rolled her into our study, and she received ruxotermatide.
00:20:04
Speaker
And what happened the next next was quite intriguing, I think. Her tumor became heavily infiltrated by cells. ah It gradually shrank and then stabilized for more than two and a half years. I don't know the latest news about her, but at that time we we followed her for a long time, or or the clinician, and the the disease stabilized for more than 2.5 years.
00:20:30
Speaker
And remarkably, her pain disappeared and she could stop all the pain medication. And she begans and she began sleeping through the night. And evan eventually, which I think was the beauty here, she returned back to playing baseball.
00:20:45
Speaker
So that was really a nice story for us and very inspiring. And so for her, it was not just about controlling this large tumor. She really got her life back. so so of course And of course, so these more personal stories like this help both me and and and our team to keep motivated to bring Ruxotermatide all the way to market.
00:21:08
Speaker
I think sometimes you you need these stories and be closer to... You are doing a lot of complex drug development.
Expanding Ruxotermatide's Applications
00:21:15
Speaker
You have investors that talk about market, but really the real inspiration to to do what we are doing is to see how you can help patients that really suffer as this young woman, for example, did. Yeah, that's ah an amazing story. Yes. yeah Without a doubt, very inspiring.
00:21:34
Speaker
And so, of course, my mind immediately goes to how do you give that to more people? um You know, rexatematide is, of course, the lead asset, but the underlying principle is broader. So how extensible do you think this approach or or this molecule is to other cancers? Yeah, so for sure, our technology is applicable for several different cancer indications.
00:21:57
Speaker
And ryksutemetide seems to be very ideal for ah skin cancer and other tumor types that can be reached ah with injection through the skin, like breast like breast cancer and head and neck cancer, for example.
00:22:13
Speaker
we We also have a second asset or drug candidate that have shown remarkable effects in cancer types that are located more deeper in the body, such as liver cancer.
00:22:25
Speaker
So indeed, our technology has the potential to be expanded across a wide range of tumor types. so And we have already proven that it works in in the skin cancer and more sub-cosidies closer to the skin. And with the same mode of action for the second asset, we believe we can see some very yeah promising yeah results in moving forward and into the clinic with the second asset. Wow. and And do you think for the liver-targeted acid, would that also be intratumoral injection? It will be intratumoral because that's the whole concept. We have taken a drug from a net nature product, and you you have to learn from the nature and not to beat the nature. This host defense peptide, we developed this ruxotermatide from, It is ah found local locally in mucosa, locally in granules and granulocytes. And when there is an inflammation, it's released locally in high concentration.
00:23:27
Speaker
So we don't believe we can beat that ah mode of action by trying to do any systemically. Maybe in the future with nanotechnology. But we think this high concentration locally makes us aware ah effect on the immune system and and kill cancer so very efficiently, even ah resistant cancer cells. so So um we believe that this local effect is is the way to go. Yeah, it makes sense. And it also limits the amount of systemic inflammation that's irrelevant to to tumor, let's say. so Exactly.
00:24:05
Speaker
Yeah, I think that sounds very, i agree with that approach from what I understand. So I'm i'm curious now, you know are are there specific tumor types or patient populations where this mechanism that um that you're advancing could have an an even bigger impact than others? Yeah, so when we when we look at the current cancer therapy process,
00:24:28
Speaker
ah challenges and also opportunity. We have seen great effect in several types of cancer with current immunotherapy. But regarding our technology, we see a very very big opportunity in patients who currently do not respond to existing immunotherapies.
00:24:48
Speaker
Because these these and these patients' population often have immune-cold or non-inflated tumors.
Future of Cancer Immunotherapy
00:24:55
Speaker
and the and And in fact, the majority of cancer patients belong to this non-responding group of patients, even though we have seen remarkable effect with the first line of of immunotherapy.
00:25:07
Speaker
ah and And we have demonstrated that all molecules can really convert cold, non-inflamed tumors into hot inflamed tumors that can better then respond to other types of immunotherapy.
00:25:20
Speaker
So our drug candidates seem to address the major challenge for this patient population that do not respond to current immunotherapy. and can increase their ability to respond to these other immunotherapies, such as Pembolicimab.
00:25:34
Speaker
And therefore we are, of course, investigating... the combination with our drug, which has proven monotherapy efficacy, episcopal effects, meaning that they reduce distant tumor, but to really improve that ah further by combining with immune checkpoint inhibitors that can remove breaks and the T cells can be allowed to work for prolonged time.
00:25:59
Speaker
I'm curious, Oistein, because you're just talking about immune checkpoint inhibitors and you know i think we all recognize that Keytruda is about to come off pattern and there's ah many, many efforts around developing other second generation immune checkpoint inhibitors. So...
00:26:19
Speaker
Do you think that this principle with combination of ruxitimitide or the other asset, 401, with other immune checkpoint inhibitors and next generation compounds is something that you may pursue in the future? Yeah, so as you as we have mentioned, immunotherapy has really transformed cancer treatment over the last 15 years.
00:26:42
Speaker
but But it has really become clear that this first wave wave of immunotherapy only helped a subset of patients. So I think there is... been after a sort of an autumn in in cancer treatment development, we are now starting to understand better the tumor microenvironment and the immune status of each patient and the role and the importance of of understand that before you give treatment.
00:27:09
Speaker
So I believe we are on the way to the science to see more smarter combination of cancer immunotherapies that are better suited for each patient based on the status on tumor microenvironment, on on the immune status and maybe even the microbiota, which I don't think we should discuss here. But there I think there are will be happening a number of new learnings here where we can make smarter combination for subpopulation of patients.
00:27:38
Speaker
And I think strongly we need a tool test of different types of immunotherapies that can activate the patient's immune system, remove the breaks in the immune system, but also help but also, and I think this is very important, to help immune cells to more efficiently be able to infiltrate the tumors for cancer cell killing, because some of the tumors have some biophysical buyer barriers that can hinder an activated immune system to to enter into the tumor. We're talking about immune excluded tumors here.
00:28:08
Speaker
So I think we will, and second, we will also see that immunotherapy will be applied in earlier stages of diseases when the patient's immune system are stronger and more likely to respond.
00:28:19
Speaker
So i I believe, I'm quite optimistic that the next decade will ah be about expanding successful immunotherapy from let's say, the more lucky responders so far to a ah more broader and higher number of patients based on better understanding of the patient's conditions in several by several means.
Conclusion and Optimism
00:28:40
Speaker
So I think it is it has been a very positive period Then some disappointments because combination therapies didn't work as they had hoped for. But no learning how you shall use the the right combination will bring us to a more positive era then in the next decade, I presume. Well, i I very much look forward to ah seeing what plays out over the next decade and what additional advancements can be made in this space because it's it's increasingly important that you know we think about cancer and in this way because it's a disease that almost all of us are going to experience at some point in time. So it's it's always reassuring to understand that you know there is so much innovation going on and that
00:29:29
Speaker
the future is looking bright. So I wanted to thank you for joining us today, Oystein, to tell us about you know your your part in in the future of immunotherapy. And we look forward to staying in touch and hearing about the updates.
00:29:44
Speaker
Thank you very much. Cool. Well, thanks again to our listeners for joining Sparktime. We welcome you to join next time as we continue to explore the ideas, the thinkers, and the innovations that drive biotech forward. We hope to see you there.