Okay, let's get started. Good morning, everybody. Welcome to the third day of the iBio Conference in Miami, Healthcare Conference. With us today is the management team of iBio. Happy to host Martin Brenner, CEO and CSO of the firm. And also with us is Felipe Duran, CFO. Gentlemen, welcome. Thank you so much for taking time out of your busy schedules to be here with us today. Before we kind of get into the nitty-gritty Q&A, we'd love to kind of get your overview of the business and what we could really look forward to in the next 12 months or so.
So iBio is an antibody discovery and therapeutics company. We're currently focusing on obesity and cardiometabolic diseases, and we've taken a slightly different approach to treating obesity than most companies did, so we early on realized that GLP-1s have actually ushered in a revolution in how we treat obesity, and we anticipated those molecules to become standard of care, so we looked very carefully at what are the gaps in patient care that these molecules leave open, and that's how we focused our pipeline, so our lead program is ` IBIO- 610. It's a long-acting Activin E antibody. It's a first and so far only in class molecule, and we have just released non-human primate PK data. It shows an extended half-life, up to 100 days predicted in humans, so that gets us in the range of maybe twice a year dosing. We're currently in CMC development and tox.
So we're anticipating to file for an IND equivalent in Australia end of 2026 with that molecule. It gets us the first patient in 2027.
I see. So maybe perhaps to kick things off, could you walk through how your discovery engine shaped the design of the long-acting Activin E and Myostatin antibodies? And what specific design choices differentiate them from a traditionally engineered antibody?
Yeah. So I'm always very careful. You're not going to hear me say we're an AI company. What we do is we do use generative AI in multiple places. What really is our niche is that we connect a network of AI tools with wet lab biology. And this deep integration allows us to focus on the outcome, which is antibodies that otherwise couldn't be made and that have high developability. So we typically start with our epitope engineering engine, which, imagine it as Google Maps for antibodies, if you will. So on drug target proteins, they're very big. And there's only small regions that convey biological action. And we select these small regions and focus our antibody discovery there. It's like typing in an address in Google Maps. And our antibodies go straight to this address, ignoring everything around.
In the worst-case scenario, that just gives us a better antibody and gets to an antibody faster. In the best-case scenario, others can't make it. And a great example is Activin E. The target has been linked to the disease three and a half years ago. So far, we're the only ones who were able to make that antibody. And this was particularly because of that part of our platform to get to this antibody. But we also have to go beyond just identifying an early antibody. We have to optimize those. And here again, we're using a combination of AI and mammalian display. The benefit of this is that we can do a so-called single-shot multidimensional optimization.
So what this means is, specifically in the case of long-acting antibodies, we don't have to take one sequence and try to optimize that for long-acting, because that actually introduces very often instability in your clone. What we do is, on a library level, look at different mutations that convey long half-life, and then basically select the best clone that has the best characteristics overall. So we can look for affinity, expression. We can look for low aggregation potential. And so on, all in one step. And that allows us to kind of get to a highly developable molecule. The trick of AI here is that we actually compress the diversity of a much larger library into a small library with the same diversity or similar, because mammalian display only takes a much, much smaller library of about a million molecules versus a billion molecules in a phage library.
Sure. I know Activin E is kind of a ubiquitous target in the body. How did you design your antibody to kind of minimize off-target effects?
So it is pretty critical for TGF-beta members. They are similar. So to really remain focused on the ones you really want to hit. Worst case, or kind of the broadest case, is a receptor antagonist that hits everything. So Bimagrumab is one example. You can have a ligand trap, Sotatercept being one example. But to engineer specifically binding in an antibody is actually the best tool. So the way we did this is we isolated a region that is very specific to Activin E that we believed had a biological function, created an engineered epitope around this, and then basically steered antibodies towards that. So it's a very unique region that we are targeting in this molecule, and that has actually delivered that molecule.
Got it. Very interesting. We're thinking about the broader obesity space. GLP-1s now kind of define the standard in obesity, at least for now. At least for now. So how do your Activin, myostatin, and Amylin programs kind of fit into that world? And what role do you see them playing in the next-gen combination regimen?
Yeah. So I think what is really important to mention is that GLP-1s are a really important class of drugs for obesity. As you said, it's standard of care. They have been tremendously helpful for a large population. But there are gaps that they have. One is obviously adverse effects: nausea, vomiting. Limits actually in the real world how much body weight people lose. It's 10% versus 20%, 25% in clinical development. So this is because patients back off of the highest dose because of the adverse effects. So an Amylin molecule that we have that is not only biased towards Amylin specificity, but literally selective for Amylin receptors and not touching calcitonin receptor, we believe that has a huge advantage. Lilly with Eloralintide has actually shown this. And they're only biased towards that. At therapeutic levels, they also hit calcitonin receptor to a degree.
Our molecule just doesn't bind it at all, so we have exquisite selectivity here, so that could be a replacement for GLP-1. It could be there's a widespread of effect sizes in GLP-1. There's people who gain 3%. There's people who lose 60%, so there's definitely a large population that would benefit from an alternative, and if the effect size is retained at a higher dose without adverse effects, Amylin could actually edge out GLP-1s in the long run. The second thing that GLP-1s really kind of leave open is with the rapid weight loss comes muscle loss, and so far, we have studies from weight cycling through diet that are actually leading to sarcopenia and to frailty fracture increase. Now, since Obesity Week, we have actually evidence that GLP-1 treatment, cessation of that years later, leads to increased fracture risk too, so we cannot ignore that anymore.
Increased fracture risk, you're saying?
Yes. Unschütz has published a poster about this. It was eye-opening. Again, not to dig the GLP-1s, but we need to have this in mind when we start treating patients, specific patients with GLP-1. Having a myostatin or myostatin Activin A bispecific molecule that protects muscle, which ultimately then protects bone density, will become probably a much more important role. Again, treatment on top of GLP-1, very likely.
Got it.
And then last but not least is the durability of the effect. We see that patients come off GLP-1 relatively quickly. And interesting story, David Kessler, former FDA Commissioner, has actually wrote a piece in The New York Times describing his own journey on GLP-1 and how he ultimately decided to not go back on drug. And I think that's something really worth kind of reading and thinking about this, that weight maintenance and the Activin E molecule, at least in rodents, have shown that we can create weight maintenance. So these mice, once we take them off of GLP-1, don't regain weight. And so that's something that is a big unmet medical need.
A huge market.
Yeah. We can talk about regulatory pathway for that. That's completely unclear. But I think this is the biggest unmet medical need we see right now. We can lose weight, diet, GLP-1, Amylin. We cannot keep the weight off. That's the problem.
Got it. And you mentioned the utility of your assets in preserving the muscle mass, its role in sarcopenia. As we think of obesity as kind of really a set of comorbid subpopulations, what specific segments do you see your programs addressing? And how do you think about tailoring accommodation for those groups?
Yeah. I think I'm glad you're asking this question, because until recently, we have treated a billion obese people worldwide as the same, which, like I said, is not true. So I think one of the key populations that is emerging is sarcopenic obese people. And an investor asked me, but that's a niche. But that's 10 million people. That's a pretty big niche. And so we feel like these patients are in dire need to lose fat mass, but they cannot afford losing more muscle. So utilizing a bispecific molecule in this case would probably be a really ideal situation. It loses your fat, increases muscle mass. I want to highlight the cardiovascular events that we're seeing. So GLP-1 is actually reducing cardiovascular risk. That is very, very positive. But we have with Activin E, for example, genetic evidence that it actually reduces cardiovascular risk, reduces metabolic disease risk.
Adding this on top of a GLP-1 might be really, really beneficial. We definitely think there's a subgroup of people that specifically have cardiovascular disease that could be segmented very nicely. Then last but not least, that's emerging biology. If you look at chronic kidney disease, which in itself is a huge market, there's a huge population that is obese and has chronic kidney disease. We know that TGF-beta family members, myostatin, and Activin A are upregulated in these diseases. Now we have the tools, the pharmacologic tools with a bispecific molecule to interrogate these diseases. The biology is very early. There might be a large population that would benefit from a bispecific molecule that is actually suffering from kidney disease on top of obesity.
Excellent. Very, very interesting. You said that in the past, you said that the myostatin program really kind of belongs with a GLP-1 franchise owner in that you're being very selective on stewardship here. So what does the right steward look like for IBIO- 600? And how are you actively pursuing that partnership today?
Felipe is really well-suited to answer that question.
We've had multiple discussions there in terms of what is the right steward, and what we believe is that the right steward is someone that wants to differentiate their GLP-1 franchise or Amylin franchise, because myostatin can be combined with both. And that differentiation is outside of dose and delivery. What does that look like? It's someone that has credibility in the obesity space. It's someone that has proven that they can provide value in co-partnerships or in licensing or co-developing an asset, and that's what we feel is the right steward for the molecule. I want to be clear. Yeah, we have been in active discussions with this molecule, but we believe that the de-risking milestone that we have with filing and accepting and potentially accepting in Australia next year could open up the doors for even potential more dialogues and maybe actionable dialogue with these partners.
Just out of curiosity, why pursue Australia first as a first foray into kind of IND?
Sure. I'll tackle it, and I'll give it to Dr. Brenner. We believe that it's a quicker path to acceptance. There's multiple reasons why. Number one, it's very proven that Australia has the population to do phase Ia studies. And there's also a tax benefit that we can provide and get an R&D credit. Secondly, we believe that from filing to acceptance would be two-to-three months versus an IND, which would be six-to-eight months. It does not mean that we are not also pursuing an IND. So we would do that right after. We also are completing the tox studies to provide to the FDA for an IND filing. So it's more of a dual path in terms of Australia as well as in the U.S.
Got it. And my next question kind of dovetails on the answer you just gave. But kind of what do you see as the fastest, I guess, most informative data package you can generate to enable meaningful partner discussions? What specific steps are you taking to kind of pull that readout forward as much as possible?
So you want me to answer that?
Please.
When we talk to partners, the entry point is always they want to see non-human primate data. But when you show them non-human primate data, they ask for phase I data. And I'm guaranteeing if we have phase I data, they're going to [crosstalk] ask for phase II data. It's the game. What we do differently is, A, the speed with which we can actually move molecules into the clinic. It's really a big advantage to get there in 18-24 months. But what we've established very early on is translational animal models. I'm sure that anybody who has worked in the biotech sector, pharma sector, and has worked in R&D has an example where a mouse model did not translate into humans. So we have almost religiously put in non-human primates as our translational model.
I think that actually creates a lot of confidence in the program if we can actually show how this looks. It's still a model. It's still not humans, but it's much, much closer.
I can only imagine the activin expression is much different in primates versus a mouse.
We know this, for example, with GDF11 and Activin A. It doesn't play a big role in a mouse, but it does in non-human primates and humans. So yes, there's clear advantages of having a solid non-human primate package. It does cost money, but it de-risks the program significantly. We can make much faster decisions as a small and nimble organization. We just shaved off seven months development time of activin E because we took some decisions at risk. We can do this because we are a small team. We are fully aligned and all pulling in one direction. That's an advantage of a small company. But most importantly, what we're seeing is because the nature of our molecules is usually long-acting, we can create phase 1 data packages. And I want to highlight really the most important thing for us is safety of the patients.
This is what a phase I is all about. We can establish the PK, the half-life in humans. But because of the long-acting nature of these molecules, what we have is we can actually look for early signs of efficacy. I want to be clear. This is not a phase II. This is not proof of concept. If we can show that, for example, fat depots shift with MRI or DEXA scans, that's early signs of efficacy that further de-risk the program. I think that's the benefit of having a long-acting molecule. We can also talk about the challenges. I think this data package going all the way to a phase I, which could be completed in $3-$5 million, is a really significant add-on in the value of the program.
I see. Excellent. Excellent. While we're on the subject of non-human primates, given the 30-plus day non-human primate half-life and roughly 50-100-day predicted human half-life, how are you structuring the first-in-human trial for 6110 so that you could safely characterize the PK and safety without really dragging out and burning too much capital?
Yeah. So we're actually in a really good position. So there's multiple long-acting antibodies that have been developed in early clinic before Depemokimab being one. But we are also in a really good situation because we have two siRNA companies. And siRNAs are likely going to be dosed twice or even once a year. That is considered a long-acting mechanism. So we're a fast follower, if you will, to clinical development, which is very good. We can sit back, watch how these clinical trials unfold. And again, if you're the first mover, you have to actually explore multiple things. And some will not work. So we're very carefully looking at Wave Life Sciences and Arrowhead, how they actually develop their clinical strategies.
Based on what we're seeing, we believe we can shave off a little bit of time, maybe quite a bit of time in clinical development just by learning what they did and because they actually had to chart the way to get there. Our phase Ia is actually quite a traditional phase Ia. It's going to be a dose escalation. We have to likely wait with the escalation until we hit Cmax and wait a week or two after. That's what we're currently anticipating before we can dose up. That doesn't prevent us from keeping to increase the dose. We will have to very likely monitor the patients much, much longer because of the long half-life. That also doesn't prevent us from actually moving on to a phase Ib. We don't see a lot of negatives.
It will take a little longer than a short-acting small molecule or once the peptide, but we don't feel like this is a negative because we will see early signs of efficacy in this study as well.
Typically, single-ascending dose trials, phase Ia trials, they usually kind of really crank up the dose as high as possible. Do you have any initial thoughts on how many cohorts that this may have or no?
So we believe three to four is what we're planning. So again, the beauty of antibodies, it's a really well-established modality. We're not in the range of five approved drugs so far. We have many approved antibodies. And we can actually learn from all of these developments and adjust our clinical trials based on that.
Got it. More of a financial question for you, Felipe. As you reposition the company around kind of long-acting metabolic programs, how are you thinking about capital strategy and kind of managing the legacy balance sheets so that you have the flexibility to advance the pipeline?
Great. So great question. I want to actually focus on the current balance sheet, not the legacy balance sheet. So with the current financing, it does allow us to extend our runway. So right now, we've given the guidance that we have cash into second quarter calendar year 2027. We just raised $100 million, $50 million upfront. $25 million warrants were tied to the acceptance of an IND equivalent. And we believe that that will occur sometime in 2026. That additional $25 million can get us through calendar year 2027. And they would advance Activin E and the bispecific. So I think that's really what positions us with some strength right now. Additionally, as you rightly said, we do have some legacy assets on the balance sheet. IBIO -100, which was part of the immuno-oncology assets that we acquired when we acquired RubrYc.
We're looking for partners for those assets so that we can really strengthen and strategize on our cardiometabolic obesity and focus on that and basically offload the immuno-oncology assets.
Got it. Felipe, I have the last question. You've spoke about non-human primate data, IND equivalent filings, first-in-human plans across 600. And so over the next 12-18 months, which one or two milestones do you see as most important for changing how partners, even investors, view the story?
Yeah, so if you will, we are a publicly listed company, preclinical, so we're in biotech purgatory right now, if you will. I think for us, the biggest change that will happen is when IBIO-600, our long-acting anti-myostatin molecule, will hit the clinic. We believe we can file end of first quarter, beginning of second quarter, which could get us to first patient dose in the first half of next year. I think that will change what the company is. First, it will validate our platform, so this is a molecule that exclusively came off the platform. That's the first clinical asset. It also will show that the team can actually execute from a paper exercise of what myostatin antibody should look like to a clinical molecule. I think that's a really, really dramatic step for iBio. It's the first time we're actually entering the clinic.
But I want to highlight the Activin E program, because again, this program or this target has been identified by two key players, Alnylam and Regeneron. And I doubt that there's a better antibody company out there than Regeneron is. But we have not seen an antibody against Activin E coming out. So being the only one in the industry to be able to make that antibody really sets us apart. It highlights what the platform can do from a capability perspective. But if you take one last step back, what we've done is we've taken actually a portfolio approach to treating obesity. So if you think about it, we have a molecule that reduces food intake with Amylin. We have a molecule that kind of causes fat-specific weight loss and potentially weight maintenance with Activin E.
We have myostatin and the bispecific that could potentially actually lead into muscle preservation. So we have a diverse set of mechanisms. Let's be real. This is early discovery and early clinical development soon. There will be failures. Not all of them will make it, but we're de-risked because we're covering multiple mechanisms. We're also de-risked from a payer perspective because we're still trying to figure out who's going to pay for obesity drugs. And it's unlikely that all of them will be covered by insurance, but it's likely that some will. So I think what we've created is kind of a de-risk portfolio that tackles obesity in a very unique way that is usually reserved for much, much larger companies.
Excellent. Well, unfortunately, that's all we have time for. But Martin, Felipe, thank you for such an excellent discussion. Thanks again also for spending time with us at our conference.
Thank you. Thank you for inviting us.