Hello everyone, welcome to Oppenheimer's 36th Annual Life Science Conference. I'm Jay Olson, one of the biotech analysts here at Oppenheimer, and it's a pleasure to welcome you to our discussion with iBio. It's an honor to introduce Martin Brenner, the CEO and CSO of iBio, and Felipe Duran, the CFO of iBio. Thank you guys so much for joining us here today. Really appreciate it, and Felipe, I'll turn it over to you.
Sounds good. Thank you very much, Jay. Just a few forward-looking statements, disclosure for legal purposes, I want to hand it over to Martin to talk a little bit about iBio's strategy and our portfolio approach. We'll get into a little bit of the inflection points that are coming up, finally, where we stand in terms of cash and things of that like. Martin.
Thank you, Felipe. Jay, thank you for having us today. I think what we've witnessed over the last five-10 years is a revolution in treating obesity. The GLP-1 class of drugs has really kind of reached efficacy levels that we could only achieve with a scalpel before and very invasive surgery. When iBio got into the space about two years ago, it was, to us, very clear these molecules would become cornerstones for obesity treatment.
Instead of focusing on competing in that space, we've looked actually beyond the GLP-1s and looked at areas of unmet patient need that these drugs don't cover. This is how we actually framed our portfolio to look beyond the GLP-1s, to have second-generation drugs that would address some of the shortcomings, but also some areas of patient care that have not been addressed. Next slide, please, Felipe. Before we get in, a real quick patient journey on a GLP-1. I want to highlight this because this is really important. This is true for so many patients. They go on a GLP-1 treatment, and they lose quite significant amounts of weight early on.
It seems to be that patients on GLP-1 actually stop the treatment after a certain amount of time, might it be 3 months, might it be up to two years, but it looks like patients ultimately come off the GLP-1s. While on the weight loss journey, and for every kilogram lost, unfortunately, a third of this lost weight is coming from muscle. Muscle is a healthy tissue. We need to retain muscle. It contains mitochondria. It makes us move around. We don't want to lose muscle. What actually makes us sick is the fat that's highly inflamed around our inner organs. That is being lost too, but there's a significant component of muscle to this.
What happens once patient stops taking the GLP-1, and that's also a part of this journey, is they regain that body weight they just lost relatively rapidly, 80% in about a year. Unfortunately, the muscle that has been lost on the way down is not regained on the way up. You can imagine, if you cycle through this multiple times, every single time you go on the weight loss journey, you start at a lower level of muscle. This, in a setting of, where patients have been just subjected to diets, has actually led to a significant increase in frailty fracture risk. As of last November, a group from in at Anschutz has actually shown that also the GLP-1s cause an increase in fracture risk as well.
This is something we don't want to raise an alarm, but we want to be aware of and want to counter these effects as soon and as fast as we can. Next slide. We have actually centered our portfolio then around prevention of lean mass loss, which is one of the adverse effects we're seeing on GLP-1 therapy. We have two programs, our myostatin molecule, IBIO-600, and also our bispecific molecule, a myostatin activin A, a bispecific antibody, that would counter these negative effects. We also have seen, and this is largely based on the recent clinical data that Eli Lilly has published on eloralintide, that there is indeed a molecule and a pathway that could lead to the same efficacy levels as a GLP-1, but with much reduced adverse effects.
We have gone one step further, and we have not just biased the molecule towards amylin receptors, away from calcitonin receptors. We have, to our knowledge, as the only company, a molecule that is exquisitely selective for amylin receptor one and three, so we're not even binding to the calcitonin receptor, which we're hoping gives an even better adverse effect profile. Last but not least, what we're seeing as one of the biggest unmet medical needs is the sustainability of weight loss. We have drugs that help us lose the body weight.
We can also go on a harsh diet, Keeping that body weight off for good, this is something we have no pharmacological intervention for, I hope I can convince you today with some data from our preclinical models on activin E, that this could actually become a drug that could be used as a weight maintenance drug. I'm fully aware there's no regulatory path at this point for a weight maintenance drug, I think the high unmet medical need will drive these decisions very quickly. Next slide, Felipe, I think I'm handing this to Felipe now, for our near-term inflection points and catalysts.
Great. Thank you, Martin. 2026 and 2027 is a very exciting time for iBio. We have multiple inflection points in the near term, I want to focus on IBIO-610. This is our long-acting activin E. We just completed our non-human primate data and are in current analysis of that data and hope to have some data readouts over the next 30 to 60 days. We plan to release more data at the upcoming ADA ObesityWeek, as well as the European Diabetic Association meeting. More to come on the non-human primate data. This program is on track to still file in Australia for an IND equivalent by the second half of 2026, towards the later half of this year.
That puts us at first patient dose in the first half of next year. Our next program, which we're excited about, and you know, yeah, it's very timely because, you know, 35Pharma was acquired yesterday by GSK, but it's our bispecific program. It's our myostatin activin A program that we are focusing on HFpEF and as well as obesity. This is about 6 months behind the activin E time frame, and we plan to have a developmental candidate, late second quarter, early third quarter of this year, rush that through CMC and tox, and have IND equivalent filing, first half of 2027 or potentially early second half of 2027. Our third asset is our long-acting myostatin, which we have labeled IBIO-600.
We are currently preparing to file in Australia, and we are on track for first patient dose sometime in the third quarter. That would mean that we would have interim data on this asset, sometime late first half of this, second half of this year, or potentially first quarter of the next calendar year, depending on how enrollment would go. Lastly, one of our partnered programs, which is our amylin program, we're extremely excited about, and I know the team in San Diego has been doing a fantastic job of optimizing those assets. That molecule is around six.
is on the same time frame as our activin, sorry, excuse me, as the bispecific. We plan to have a developmental candidate in the coming quarters, and rush that also through CMC and tox, and hopefully have IND equivalent filing in the second half of next year. Very exciting times for iBio. I want to hand it over to Martin to talk a little bit about our activin E program and some of the data that we've been seeing.
Thank you, Felipe. activin E is a really interesting target in the obesity space. it is not only one of the best validated targets that we have, genetically validated targets, because not only activin E as the ligand to a receptor is correlated with disease in the same way as its receptor ALK7. this makes it a very, very strong case for genetic validation. reduction in function of either activin E or ALK7 actually leads to protection in humans against cardiovascular disease, type two diabetes, and it shifts actually the hip to waist ratio adjusted BMI, which is a measure of metabolic and cardiovascular health. from a perspective of genetic validation, this is a very, very strong case. We believe this mechanism leads to fat-specific weight loss. As I indicated, muscle is a pretty healthy tissue.
Bone is healthy tissue. We need to retain bone density. What really kind of drives all of the comorbidities in obesity is actually the highly inflamed visceral fat around our organs. We believe this could be a fat-specific mechanism that does not touch muscle, but selectively reduces these harmful fat depots. We are in a very lucky position to have two exceptional companies that are currently actually providing clinical proof of concept and at the same time also charting a path for potential clinical development with Wave and Arrowhead. Both are pursuing an siRNA approach. This is basically reducing the target in the liver, whereas we are pursuing an antibody approach, where we're actually targeting the secreted protein in blood. Next slide, please.
We do believe that with an antibody approach, there's a theoretical possibility that we can actually reduce activin E molecules nearly completely, so that the pathway inhibition could get to nearly 100%. We've also seen from the siRNAs that they reach target engagement or target reduction about 85%, and this is now across two different companies. It seems to be kind of a natural level where liver-targeted siRNAs can go from an inhibition level. If there is efficacy to be gained from going beyond the 85% inhibition, an antibody could have actually an advantage in this, in this case, on the efficacy side. This obviously has to be proven in humans. At the moment, we're basing this on rodent data and dose response studies in rodents.
I mentioned already, kind of the fat-specific weight loss is really the key driver for this program and the key benefit. Also, it is very synergistic to be used with existing drugs like amylin or GLP-1s, because our body weights are dependent on two factors. One is energy intake. GLP-1 and amylin take care of that, they reduce that. The other factor is actually the increased energy expenditure. Humans are evolutionary driven, that if there is no food, no substrate available, to go into energy preservation. This is why we're leveling out with our body weight after taking a GLP-1. If you add an activin E molecule, you actually reduce that lower bottom. You can actually drive the body weight further down. I'm going to show you some rodent data about this in a few minutes.
We believe there's three use cases for this drug. One is the standalone therapy. We don't know yet if and how much body weight loss a monotherapy could drive, but given this is the only approval path for an obesity drug right now, this is what we have to achieve. The next use case is obviously the combination with a GLP-1, or an incretin or an amylin, which would be very beneficial. The last, and we believe the most valuable part, is to drive and keep the body weight down after we lost it. It's the biggest unmet medical need we see right now, in obesity. We are fully prepared to treat a very large population of patients. There is now 1 billion obese people worldwide.
The treatable population is probably in the range of 100 to 200 million people. Antibodies are a well-established modality by now, and we've been making antibodies for large indications for a long, long time. We believe, given the global infrastructure and the nonlinear scalability of antibodies, going from small batches to very, very large batches gives us a lot of flexibility to quickly put a product on the market once we get to an approved drug. Felipe, next slide, please. I want to highlight really quick, and I promise I will not go too deep into the science, but I want to show on a rodent data level the 3 use cases that I just mentioned.
One is the monotherapy. If I can point your attention to the lower left of the slide, we've actually treated mice that have been induced to be very obese with the antibody, and you can see in the orange curve over a four week time period, this antibody, these mice lose roughly 9% of their body weight. This is very much in line with what other companies, Wave Life Sciences and Arrowhead have shown. We feel we're in the same ballpark when it comes to efficacy. I want to highlight mouse biology is sometimes tricky to translate to humans, so we do need to do the human study, so we cannot just assume that we're going to see 10% weight loss.
It is dangerous because we have other mechanisms that worked in the past through mouse fat cells that did not one-to-one translate to humans. The verdict is really still out, and that's why we do these Phase I studies in humans. Next slide, please. Second use case is the combination with an incretin, and what you see here on the lower left is in black, we treated the same obese mice with semaglutide as an example for an incretin, and usually you expect somewhere between 15% and 30% weight loss. We're hitting this at the upper end. The IO mice, diet-induced obese mice, can be a little variable. So we're still in the ballpark, but we're at the higher end of the weight loss.
You can see if we add the antibody, and that's the purple curve, to the semaglutide, you see a further reduction in body weight loss. So we believe this could either lead to a reduced dose of GLP-1 in the clinic or in real-world settings, which would take away some, if not all, of the adverse effects. It also could be used to kind of further drive down body weight overall. What is important is the graph in the middle. We do not see further reduction in food intake. This speaks to the two mechanisms doing different things and being actually perfect to be combined with each other. Next slide. The last use case that I want to mention and show data for is the weight maintenance.
You can see here in the top left, there's a yellow box, and so we treated again, diet-induced obese mice with semaglutide, and like with another 1,000 studies that have been published, we could drop the body weight really, really rapidly. We stopped the treatment on day 14 and let the mice rebound. In black, you see what happens if they're untreated, and they rebound. If you remember the human graph that I showed you, the representation of the human body weight regain, this is basically an exact copy. The time frame is obviously compressed because mouse lifespans are much shorter, but these mice regain almost all of their body weight in a short amount of time. Now, in purple, these mice have actually received the antibody, and you can see, after a short adjustment period, their body weight levels out.
They maintain a lower body weight for a continued time, and this is what gives us hope that this could actually be used ultimately, if this data translates to humans, as a weight maintenance drug. Felipe, I think this is one. Yes. Obviously, a tremendous advantage for patients that actually receive siRNA treatment is that it can be used very infrequently, might it be quarterly, might it be every six months, might it be even once a year. For us, what was really important in designing and engineering our antibody was that we would get very close to a twice-a-year dosing or even to twice a year dosing.
What we've done is we've done a PK study in non-human primates, and the data is, you can see on the right side in this graph. We calculated the human half-life, the non-human primate half-life to be 33.2 days. Just as a frame of reference, typical fully human antibodies have a half-life of 1.2 to 14 days in non-human primates, so we're significantly above this. Now, there's two ways to kind of predict human half-life from this data. The one we used first was at the top on the left side. These are all antibodies that are similarly half-life extended than our IBIO-610, and they have measured non-human primate and human half-life and the correlation line between them.
We just plotted IBIO-610 on this line, with its 33.2 days of half-life in non-human primates, and that predicts a half-life of around 100 days in humans. The traditional way of doing allometric scaling for antibodies is the formula you see at the bottom on the left side, but that assumes the half-life of antibodies to be around two weeks, not about around four weeks, and this is why it's likely underestimating the half-life, but this is the lower number you see, the 47 days. We would not push aggressively towards 100.
We assume that we're somewhere in the 55 to 75 day range in humans, but that gets us in good company and puts us in good company with other antibodies that are actually being dosed twice a year and have a half-life between 38.5 and 50 days. We're well in this range where other antibodies can be dosed twice a year. Again, we have to prove this in humans first, but it's a good indicator that this might actually be a twice a year molecule. I want to shift very quickly onto our HFpEF and PH HFpEF program. As you are aware, HFpEF is the fastest-growing disease among the cardiovascular diseases.
For PH-HFpEF, all we had at our disposal as treatment options were basically offloading the pressure on the heart. Diuretics would work, but they would just basically treat the symptoms. PH-HFpEF is a multi-organ, a systemic disease that actually is driven by tissue remodeling. When Merck entered the space with sotatercept, which is a ligand trap for TGF-β family members, this was the first disease-modifying drug we have seen. It is very, very powerful in actually reversing some of the effects that patients experience. Patients that can't even, you know, stand up out of a chair can walk again for 60 yards. It's life-changing medicines for these patients.
Unfortunately, ligand traps are very, very complicated to engineer, and sotatercept carries, because of the inhibition of BMP9 and 10, some bleeding risk. As you remember, Keros was another company that put a lot of effort into engineering an improved ligand trap, and unfortunately had to stop their clinical trials as well. It just highlights how complicated it is to design a ligand trap and engineer out the potential adverse effects. We're approaching this from a different angle. Instead of trying to engineer efficacy out of a ligand trap, we're trying to just engineer antibodies that hit the pathways that we are aware and know are contributing to the disease. Based on our knowledge, it is myostatin, GDF11, and activin A that play major roles in the tissue remodeling in PH-HFpEF.
Instead of trying to make a ligand trap and eliminate binding to other TGF-β family members, we have actually created bispecific molecules that hit all of these three pathways, and this way, we can much more precisely steer towards that. Our hope is to see similar efficacy that sotatercept, but we're not limited on a dose level by a bleeding risk because these molecules do not bind BMP9 and BMP10. We're very early in development. We're just purifying the first 200 constructs, but we're ready to kind of move these into animal testing within the next few months. The last program I want to highlight is our amylin program, as I mentioned before.
Because we're seeing very, very positive data, amylin has more or less moved from a niche product that we felt could be used for patients that do not respond to GLP-1 or cannot tolerate GLP-1, to now a molecule, given the eloralintide adverse effect profile, plus its efficacy, that could actually capture quite a significant market share from the GLP-1 and the incretin molecules. Eloralintide is really known for biasing its action towards the amylin receptor, and there's three amylin receptors. We know that amylin receptor one and three play major roles, and then there's the calcitonin receptor. At therapeutic levels, obviously, all of the peptide drugs still kind of, you know, tickle the calcitonin receptor. This is why we have approached this very differently and made an antibody drug against the amylin receptors.
We had to solve two really critical issues. Issue number one was we wanted to hit amylin receptor 1 and 3. Our antibodies initially were so precise, they only picked up either amylin one or amylin three. We had to actually reduce the selectivity of the molecule to hit both receptors. Once we had achieved this, we struggled with the next issue, which was we had purely human selective molecules. They did not cross-react with rat receptors or non-human primates, that actually does not allow us to test these molecules in preclinical models. We had to take another run to kind of introduce into our antibody design, that we now can actually cross-react between rats, between non-human primates and humans, to actually be able to fully test these molecules.
Felipe, if you want to flip to the last slide, I want to highlight here very early data, what you're seeing on the left side is what I just said. We are exquisitely selective for amylin receptor 1 and 3. This is binding to the receptor, you can see the black curve at the bottom is calcitonin receptor. There's no binding to the calcitonin receptor, this is an exquisitely selective molecule. Binding is one piece of agonizing a receptor. Receptor agonism is the other one, that's what you see on the right side, our antibody peptide fusion in the orange line, we've chosen amylin receptor three as a surrogate here, didn't show amylin one and three, this is just amylin receptor three. You can clearly see we are agonizing this receptor.
At the same time, you see at the bottom, again, the black line, the calcitonin receptor is not agonized at all. As an example for a non-biased molecule, we've used cagrilintide, which is on the right side, and you can see in orange, it stimulates amylin receptor, but it also significantly stimulates the calcitonin receptor, which is the black curve at the bottom. Felipe, I'm gonna hand this back to you for closing comments.
Thank you, Martin. High level, we have the right team, Martin, myself, and our third C-suite, Mark. We've been in the industry for a very long time. Very experienced team. We are very well capitalized. We have cash into first quarter calendar year 2028. That allows us to drive all the assets that we talked about into Phase l, as well as completion of CMC and tox for amylin. We have a very low float. We have 34.5 million shares outstanding. Fully diluted, we are a $500 million market cap company. The way that we structured the last raise allows us to basically state that as a lot of it were pre-funded warrants.
Jay, I'll maybe open it up to you if there's any questions or any comments that you might want to have.
Excellent. Thank you so much, Felipe and Martin. Really appreciate you guys bringing us up to speed on all the impressive progress you're making at iBio, and wow, there's a lot to digest there. Thanks, Felipe, for pointing out that it's a $500 million market cap company. That is really good for investors to know. We do have a few questions. Maybe just starting off with, Felipe, you also mentioned that there would be some additional NHP data for 610 sometime this year. Could you maybe, I guess,
Sure
... investors some idea of what they should focus on in that data, and kind of how would you set expectations there?
Great. Obviously, Arrowhead and Wave have already read out in humans, the non-human primate data for us is really climactic. We really just want to maintain that this pathway works with an antibody approach. We are gonna have a stepped wide approach on this. We will put out some DEXA and MRI data, like I said, over the next 30 to 60 days. As the team continues to look at the biomarkers from the blood, from the non-human primates, we will release additional data at ADA, at Obesity Week, as well as the European Diabetic Association Conference in Europe. You know, it's gonna be step-wised. It's a very complex study that we did over 24 weeks.
A lot of different points in time that we need to look at, but we plan to have at least the first cut of that in the next 30-60 days.
Okay, excellent. We're looking forward to that. Also, if you could talk about any of the gating factors to your IND or IND equivalent submission for 610, and then I guess looking ahead to your phase l study for 610, what are some of the learnings that you've captured from Arrowhead and Wave that can be leveraged to refine your own-
Yeah
clinical development plan?
That's a very good question, Jay. First of all, from a development standpoint, we are currently in IND enabling. We have completed those range-finding studies, and we will commence GLP toxicology studies in the summer. We are in the process of creating our master cell bank. The molecule is very well behaved in early CMC essays, and we're expecting filing at the end of this year and in Australia. At the moment, there's no, you know, no issues that we are foreseeing that would slow us down in filing this molecule. Again, we have to get through safety, I want to highlight that, but nothing so far that would kind of point towards any trouble and delays.
We are obviously watching this space very carefully, as I mentioned, luckily, Wave has created the first proof of concept in humans with their study. We've seen from Arrowhead that they have now gone a step beyond, this is the beauty of us being a fast follower. We have very carefully watched the data from Wave, we've drawn some significant conclusions from this. Number one is, Arrowhead has actually expanded the areas of disease or created subpopulations in obesity, where we are now thinking about MASH as a potential indication given the liver fat reduction. We are thinking about type two diabetes very carefully. As you know, type two diabetes, the diagnosis is a point of no return.
If you have two patients, similar obesity, one is diabetic, one is not, the person with diabetes is resistant to exercise, resistant to body weight loss through diet, and resistant to GLP-1 treatment. Wave has shown, this is very early, small data set, but still what they've shown is they re-sensitized patients to GLP-1 treatment. If this holds true, we might actually see and have a treatment for type two diabetes that is disease modifying for the first time in over 100 years of research in type two diabetes. That path for these patients is very clear. Once you get diagnosed, it's very clear when you go on orals, when you go on insulin, and when your diabetic complications set in if you're not controlled well.
If we can turn that clock back, if we can flip the switch back only for a few years, this would be a dramatic expansion of where activin A could be used and a dramatic improvement of life for all type 2 diabetic patients worldwide. We haven't thought yet about cardiovascular disease because the genetic points to this. We used a monkey study to actually look for biomarkers, what kind of that disease would be. You can imagine conversations I have with Felipe are mainly focusing around how much money do we need to spend on our Phase lla. Thank you, Arrowhead, because it's a growing disease, a number of disease areas that we want to cover. Obviously, we want to help and contribute to this field as well and also expand the knowledge.
I think we all benefit from this, working together on this, and we're grateful that we do not have to spearhead everything in this space. As a small company, we like to learn from others, like to actually pick up the great improvements that we're seeing and even expand on them. I think that helps all patients, if this is kind of a concerted effort.
Excellent. Thank you so much for sharing those insights. That's super helpful. Maybe if I could squeeze in one more question, and thank Felipe again for mentioning that GSK deal yesterday. I guess, can you comment further on the read-across from the acquisition of 35Pharma to your own myostatin activin A bispecific program? Also any, I guess, additional comparisons you could make between your own program and Merck's sotatercept. You mentioned the potential for disease modification with less bleeding risk. Are there any other potentially significant differences?
Felipe, I'll answer first, but you please chime in. From a mechanistic perspective, Jay, not a concern, but what we have to work out is, can we get to the same efficacy? Are there other TGF-β family members that sotatercept blocks that we might not even be aware of? That obviously could eat into our efficacy. But we have actually done these studies very carefully with several TGF-β members and looked carefully at fibrosis of cardiac fibroblasts, and I think we understand relatively well which parameters, which TGF-β family members contribute to efficacy. But there's a risk that, you know, we don't capture everything. Luckily, we have antibodies against other TGF-β family members, and we can test combinations in these disease models.
That's why we really, you know, we don't want to move a molecule forward unless we're sure we can actually work on the same level. I think a very easy comparison would be, can we get in a simple animal model to a similar efficacy? Can we get in another animal model? Can we stay away from a bleeding risk? Because you can induce bleeding in these preclinical models, and that would be a good starting point. Apart from that, it's classic pharmacology. We need to show that our molecule is in the body, in the bloodstream, that we have target engagement, and that we collect the right biomarkers. I think there's a nice blueprint in this space, given what Merck has actually done.
Excellent. Thank you. Felipe, anything you'd add?
No, nothing that Martin hasn't covered. You know, I would let the scientist speak versus the finance person on differentiation.
Maybe, Felipe, are there other companies around us that are still standing on that space, right? I think we're getting very quickly to the end of the flagpole. It looks like we might be the only ones.
There's, there's-
with a molecule in play.
There's one or two more that we know of that we've been following, with different molecules. Yes, Martin, I think, you're right. I think we're the one that could be differentiated in that space and puts us primed for, you know, potential strategic partners once we can get into the clinic with this asset.
Okay, excellent. Well, there's a lot to look forward to here. We'll wrap things up. I want to thank you both. Martin, Felipe, thank you so much for bringing us up to speed on all the great work you guys are doing at iBio. Thanks, everyone, for joining us here today.
Thank you, Jay, for having us.
Thanks, Jay.
Our pleasure.