Good afternoon, everyone, and thank you for joining us for another session of H.C. Wainwright's 26th Annual Global Investment Conference. My name is Eduardo Martinez. I'm a Biotechnology Equity Research Associate with H.C. Wainwright, and it is my pleasure to introduce Mr. Carmine Stengone as Founder, president, and CEO of Contineum Therapeutics. Mr. Stengone, you have the floor.
Well done. Thank you. Well, thank you to the H.C. Wainwright team and for everyone in here. Very quick legal disclosure. I'll just skip through. I know that we're limited to 20 minutes, and I can drone on, so I will try and hit the high points as much as I can and hopefully end with some of the key catalysts that we have coming up. So Contineum Therapeutics, we're a San Diego-based drug discovery company, drug discovery and development company, focused within the area of NI&I, so neuroscience, inflammation, and immunology. I'll spend the bulk of today's discussion focusing on our two clinical stage assets and the 4 diseases that we'll be pursuing with those assets. But I wanna get a few things out off the bat.
So first of all, we try to focus as much as we can on clinical de-risking at an early stage. We do this through three different ways. So as we talk about PIPE-307 and PIPE-791, in the four indications that we're looking at, three of these have clinical validation, and we think that that is absolutely critical in de-risking these targets as we push them forward and come up with best-in-class approaches. A second thing that we look at here is when we investigate other compounds, other companies, we notice that a lot of drugs die in phase II. Some of this is due to missing the dose. We wanna make sure that we fully understand the dose-receptor occupancy relationship before we move into a phase II clinical proof of concept study.
So with 307, we ran a PET study to fully understand the receptor occupancy for an impact in remyelination, as well as an impact in depression. We're going through that same approach with PIPE-791, kicking off proof of concept studies coming up. And then lastly, this was probably most relevant with 307. In the clinic, we'll run kill studies as soon as we can. So one of the big questions with antimuscarinic drugs is: Is there a cognitive liability associated with antagonizing these targets? It was our thesis heading in that if we can selectively hit one of the five muscarinic receptors, we can avoid any sort of cognitive issue. We tested that out in our phase I.
Every patient in that study went through a cognitive battery of tests, and there was no difference between the subjects and the placebo group. The markets that we're looking into, everything starts with a neuroscience target. PIPE-307 was chosen because of its clinical validation and impact in remyelination. M1 receptor antagonism is solely CNS-based. We are currently in a phase II clinical proof of concept study with PIPE-307. This is a first-in-class selective inhibitor of the M1 receptor. We are running a phase II relapsing-remitting study that will complete enrollment next year, and with our partner, J&J, we'll be kicking off a phase II clinical proof of concept study in depression later this year. With 791, this is a first-in-class brain-penetrant inhibitor of the LPA1 receptor.
You may be familiar with LPA1 receptors from BMS and from Amgen, focused in IPF, and we'll talk about that in a bit. But as I said, we start with a CNS angle, and the reason that we liked LPA1 as a target was given the expression profile of this target in the brain and specifically on glial cells. So by inhibiting LPA1 in the brain, we can lead to remyelination through oligodendrocytes, but probably more importantly, in a progressive MS setting, we can also lead to a reduction in neuroinflammation, given the target's profile in the microglia. So with these programs, there's multiple shots on goal. These are all large markets, huge unmet medical needs, especially when we talk about progressive MS and IPF. The IPF drugs out there, we'll go into in a bit of detail, but they're not tolerable. They aren't very effective.
Even with one drug approved in a progressive MS setting in Ocrevus, if you look at the phase III data that led to that approval, the disability, the change in disability between drug and placebo was 39%- 33%, so a pretty minor change. And we believe that that is. That can be improved upon with a true reduction in neuroinflammation. Everything that we have done has been developed in-house. So for PIPE-307, we have patent protection without patent term extensions through 2040, and similarly with PIPE-791, we have patent coverage through 2042 prior to patent term extensions. We are one of the few companies that went public in 2024, so, we completed our IPO in the first half of April.
We've raised. We netted about $110 million in that. We went into the process with over $120 million in the bank as well, so we were well-capitalized heading in. Given where we are and the clinical development programs that we will be pursuing, we can provide guidance of cash through 2027. So a bit on the portfolio. Just I'll run through this. I think I went through most of this, but PIPE-791, again, first-in-class brain-penetrant inhibitor of the LPA1 receptor. We are advancing this in progressive MS and both primary and secondary progressive. We will also be looking at the PIPE-791 in idiopathic pulmonary fibrosis and subsequently in progressive pulmonary fibrosis as well. The clinical validation for this target in the IPF space is indisputable.
If we look at the two BMS drugs that have reported phase II data in 500 patients, it's clear that this target works in IPF. But the profile of those compounds are less than ideal, and we believe that, using a drug like PIPE-791, with the ability to achieve EC90 coverage 24 hours a day in a QD dosing regimen, can change the treatment paradigm for these patients. We are completing a phase 1b PET study in healthy volunteers later this year, and we will also look at patients in the first part of next year. In the first part of next year, we will also complete the chronic tox on PIPE-791, and that leads us into two larger scale phase II clinical proof of concept studies in 2025 for PIPE-791 in IPF and progressive MS.
As I mentioned, 791 is a brain-penetrant compound. From a strategic perspective, as well as from an Inflation Reduction Act perspective, we used our chemistry team to identify a compound with very similar properties to 791, but it is peripherally restricted. So we nominated PIPE-343. I'm sorry, CTX-343, earlier this year. We will file the IND in the middle of next year and complete the healthy volunteer study in CTX-343 next year as well. Then lastly, PIPE-307, first-in-class selective inhibitor of the M1 receptor. This target actually led to the foundation of Contineum Therapeutics. We were very interested in inhibiting the M1 receptor on oligodendrocyte precursor cells, so cells that are fated to become fully functional and remyelinating oligodendrocytes.
It was over the course of that, that we had a lot of strategic interest around this. We completed a partnership with J&J in the first half of last year, a $1.1 billion deal, $50 million upfront, $25 million in equity that came into the company, as well as support into the IPO. They have clinical validation through one of their investigators when he was at NIH, demonstrating M1 receptor antagonism has a rapid and robust impact in a range of different depressive disorders. And unfortunately, I'm limited in everything that I can say due to the J&J deal. I know we've got a small group in here. I'm happy to continue going, but if there are any questions, because I've kind of gone on for a little bit, I'm happy to take any. Okay, I'll move on.
A little bit about IPF. This is a rare, fatal interstitial lung disease. Now, some of the stats around IPF are pretty stark. There's about 130,000 patients in the United States, 3 million worldwide. When you're diagnosed with IPF, it is a death sentence. Even with the current treatments out there, the time frame from diagnosis to death is on average about three years. We have two drugs out there, one called OFEV from BI, and another one, pirfenidone, that was from Roche, which is now generic. Frankly, the efficacy profile on these is somewhat weak. The tolerability profiles are even worse.
So if you look at the patient populations who are eligible for treatment, anywhere from 30%-50% refuse to go on treatment because of the side effect profile, and another 50% roll off of drug within a year. So this is really an untapped market. And despite these limitations with the current therapies, I think the OFEV drug is projected to do over $5 billion in sales this year. So we have clinical validation with a safer QD dose of an LPA1 receptor antagonist that we think can help change the playing field for IPF patients. So a little bit about the mechanism of why an LPA1 receptor antagonist works in this disease. So a lot of this was teased out by Andy Tager at Harvard Medical School in two thousand and eight.
What he was able to show is that lung injury leads to an increase in LPA and then activation of the LPA1 receptor. And it's through that mechanism where we have an impact on fibroblasts, so increased fibroblast accumulation, and then subsequently fibrosis associated with that. So by inhibiting the LPA1 receptor, we can limit what LPA does and have an impact here. LPA also leads to vascular permeability that leads to inflammation also associated with idiopathic pulmonary fibrosis. So just touching on the clinical validation for LPA1 in IPF. So as I mentioned before, BMS has had two drugs go into the clinic for idiopathic pulmonary fibrosis, both LPA1 receptor antagonists.
Interestingly, BMS-020, the first drug to have gone in, originated with Contineum scientists at Amira Biosciences, and Amira sold to BMS back in, I think it was 2012, for about $500 million for that program. On the in the middle bar chart there, you can see the data that came through the phase II study. So we know that BMS, or that BMS and/or Amira did a PET study heading into this, and they were able to select doses that had a pretty nice impact here. High doses, it's a highly protein-bound compound, but at 600 mg QD and 600 mg BID, you see a really nice improvement in FVC decline. The issue with this drug is it-...
It had an off-target liability against BSEP, so bile salt export pump, that led to hepatobiliary tox, and subsequently, that drug was discontinued. BMS liked the target enough, they went and they discovered their own compound. And on the right side is data that was presented last year at ATS with BMS-278. And as I mentioned before, we want to clinically de-risk heading into the phase II. In this case, we think they missed their dose. So they went into this study with a 30 mg BID and a 60 mg BID. If you look at the 30 mg BID, the green line in the middle, it has no difference than the placebo. The 60 mg BID starts to show an impact. It is not as efficacious as zero two zero.
So now they're moving into a phase III, and in the phase III, they're dropping the 30 mg BID, they're doing a 60 mg BID, and now they're also adding a previously untested dose in patients in 120 mg BID. We also believe that they may have a hypotension signal that we don't know if it is target related or not, but we have not seen any cardiac events out of our phase I. Just jumping through a bit. The other important thing on the PET study is we can really help to understand the receptor occupancy curves and how that can change the fibrotic changes in patients. So on the left side, this is a pretty common bleomycin-induced lung fibrosis model.
We show a dose relationship related to the increase in receptor occupancy, where we're able to maximize the anti-fibrotic potential of an LPA1 receptor. We believe that we're the only group who can achieve 90%+ coverage in patients. We had our phase I study earlier this year. We did four MAD doses. We did three. I'm sorry, four SAD doses, three MAD doses. We did a fed study as well. On the right side, you can see the treatment-emergent adverse events associated with the drug in more than two or more subjects. Really, we didn't see anything at all here, nothing that you wouldn't expect out of a typical quarantined healthy volunteer study. No dose-limiting AEs or toxicity, no changes in clin labs, telemetry, or vital signs. The database was locked earlier this year.
I think the most important slide for PIPE-791 is this one. So what we learned with this compound, and allows for a low-dose QD dose regimen, is that it has a very slow association and dissociation rate. It's not a covalent binder. It does dissociate over time. But given that property, we have a very flat peak-to-trough ratio, and you can see that some of that demonstrated on the half-life of anywhere from 31-55 hours, depending on the dose and the SAD. So on the left side, on the SAD, the lowest dose is in the yellow, one milligram. You can see, we can still see drug on board in these subjects all the way out to 14 days. More importantly is the right side. So here we're mapping the PK out of the MAD cohorts across the projected EC50 and EC90.
The solid circles are the PK profiles from day one for each of these doses. The open circles are the last day of dosing, so seven days for the 1 mg and 3 mg and 14 days for the 10 mg. And you can see with a single dose of PIPE-791, on day one, we are able to achieve EC90 coverage. And as we look at the repeat dosing, you're seeing orders of magnitude improvement there, and all these doses were safe. So the next step is moving into our PET study, where we will validate these results both in lung and in brain. And then in the middle of 2025, we'll be kicking off a phase II clinical proof of concept study in this indication. Sorry, I know I'm going to have to jump through some of this as well.
Just to touch on 791 and its impact in the CNS. Our interest here is not only for neuroinflammation, but also on remyelination. On the left side, we use a functional biomarker of remyelination called VEP latency, so visual evoked potential latency. In MS patients, there is a demyelination of the optic nerve, so the conduction velocity from the retina to the visual cortex is stunted. With a remyelinating agent, you can reverse that, and you can see on the left side, from a VEP perspective, we're able to normalize these animals back to control levels. In the middle is increased myelination. In these animals, we can do histology, show an increase in remyelination, and importantly, on the right side, a reduction in neuroinflammation. In the left panel, that's through Iba-1 positive cells.
On the right side, an LPS challenge model across a range of different insults. So the focus for this program will be on remyelination, so the typical six-month remyelination metrics, looking at low contrast letter acuity, MSFC, the MS functional composite, EDSS, and NfL. But importantly, from the neuroinflammation standpoint, we will focus on paramagnetic lesions. So these are lesions that are visualized due to the impact of microglia. So it's a microglial iron lesion, and what we want to be able to demonstrate is a reduction in those lesions over the course of this study. I know I'm running low on time. Just to... We touched on the J&J collaboration. We had confidence in doing this collaboration because we saw the profile of seven nine one coming out.
Importantly here, with 791 , the disease areas are diseases that can be handled by a smaller company. With 307 , looking into relapsing-remitting as well as a broader depression program, J&J was the perfect partner for this. So this was a global licensing collaboration, about $1.1 billion in milestones, royalties that ramp into the high teens. We hold on to a co-development option that kicks in at the phase III that allows us to pump those royalties even further. So I will just jump to... The key clinical milestones coming up. So 2025 will be a heavy clinical lift for the company. We'll have two clinical programs running and hopefully completing enrollment in 2025 for 307 . We will complete two versions of the PET study.
That includes the phase 1b healthy volunteer, as well as the study in IPF and progressive MS patients. We will have a phase I completion for CTX-343, and then we'll kick off the two 791 studies, and we are considering an exploratory study and another indication for PIPE-791. We haven't been public about what that is yet. So looks like we're down to our last 10 seconds. I'm happy to take any questions.