Great. Welcome back, everyone, to another session here at Oppenheimer's 35th Annual Life Sciences Healthcare Conference. I'm Leland Gershell. I'm one of the analysts here on the Biotech Equity Research team. Up as our next presenting company is Entera Bio. Entera is developing a number of oral peptide therapeutics to address important conditions. On behalf of Entera, we have the company CEO, Miranda Toledano, who will walk us through her slides and remarks. We will have some time for Q&A. Please submit any questions you'd like, and I will do my best to ask those on your behalf. With that, I'll turn the podium over to Miranda. Thank you very much, Leland. Thank you for the opportunity to present Entera. I'll be making some forward-looking statements, and I encourage everyone to review our SEC filings. As Leland noted, Entera is a company that focuses on the development of simple mini-tablet formats of peptides. We have programs now across gynecology, endocrinology, GI, and metabolic diseases. The way that we select these programs is we focus on understanding the underlying peptide target and making sure it aligns with our technology platform, with the hope of developing a therapeutic that can drive superior health outcomes and really change treatment paradigms. Our lead clinical candidate, we call EB613, is the first PTH(1-34) osteoanabolic bone-forming tablet treatment, which we're developing to address the treatment chasm that we see in postmenopausal women with osteoporosis. We are planning to initiate a phase three of this program in the second half of 2025. A quick look at our technology, which we call NTAB. Essentially, what NTAB enables us to do is develop, at the end of the day, a mini-tablet format of a peptide. The two main mechanisms of action of our technology are looking to stop the proteolytic inhibition of the peptide to maintain its stability as it goes through the GI tract. Also, we increase the transcellular permeability via a SNAC in order to really create an oral peptide in a tablet format that can both get into the bloodstream and induce a therapeutic effect. This is a quick look at our pipeline, and I'm going to spend quite a lot of time on 613, so I'll skip through it. That is our lead clinical candidate, which is the only PTH(1-34) tablet. I would just mention that each of these programs has a different backbone. Each of these programs is a pure peptide program. These are not small molecules. These are not hybrid molecules. These are actually underlying peptides that we combine with the NTAB technology using specific differentiated excipients to solve for different characteristics of the underlying peptides. We have a second program, which we call 612, which is looking at the treatment of hypoparathyroidism. In that indication, we have two strategies. We have an organic program using an unmodified PTH(1-34) peptide with a different backbone to 613, which we completed a phase one study, twice-a-day dosing in 2023. More importantly, we've been focusing our attention for the past year to an undisclosed collaboration where we have identified a different PTH(1-34) targeted peptide where we believe the PK/PD of that peptide will enable us to achieve once-a-day tablet dosing. Our goal across all of these programs is once-a-day dosing. In late 2023, we formed a partnership with OPCO, and we are co-developing two programs together. One of them is Exintemodulin, which is a dual-target, a GLP-1 glucagon agonist, which we're looking at for metabolic diseases, fibrotic diseases of obesity and obesity. We have a second program in partnership with OPCO, which is a GLP-2 focus program, which is being looked at for short bowel syndrome and other gastromucosal inflammatory disorders. Potentially, both of those programs are entering a pre-IND stage. Let's dive in a bit more into 613. 613 is being developed as the first once-daily osteoanabolic tablet for postmenopausal women. Osteoporosis, for those not as familiar with the disease, is an enormous disease which afflicts mainly women, 80% of patients globally, if not more, are women. It afflicts more women than heart attack, stroke, and breast cancer combined, about 200 million women globally. 50% of women over the age of 50 will experience an osteoporosis-related fracture, and about a billion women are set to enter menopause. In spite of the current treatments, which we'll go through in a moment, there remains a significant majority of patients remain untreated. This has led to continuous increases in fracture rates, continuous increases in mortality and morbidity attributed to this disease. This is a disease also which has lethal consequences. About 20% of patients, adults that sustain a hip fracture, die within 12 months, even with surgical intervention, and 60% die within a year without surgical intervention and proper therapeutic intervention. Osteoporosis, just from a biological basis, it occurs when the normal bone remodeling cycle, which happens from the minute we're born until we die, is disrupted. The rate of bone resorption or bone degradation outpaces bone formation, and that leads to osteoporosis, and patients become losing bone mineral density and becoming more and more susceptible to fracture, fracture just being another word for bones breaking. The way these patients are routinely diagnosed, staged, and managed is via bone mineral density testing, which simply requires an X-ray DEXA scan in order to measure the bone mineral content and density of the bone and really determine whether a patient is at risk of osteoporosis. A T-score on the right side of minus 2.5 and below determines diagnosis of osteoporosis. The way that this disease is currently treated is basically divided into the two mechanisms of action, which the gray boxes are the anti-resorptive drugs. These are drugs that deter the degradation of the bone. The most commonly used are the bisphosphonates and Prolia. On the right side are the blue boxes, the injectable anabolics. These are drugs that actually have an anabolic and bone-forming function, as well as repair and ameliorate the microarchitecture of the bone. The three approved drugs all require daily or monthly injections. When we look at treatment trends across not just the U.S., but most geographies, but just taking the U.S. kind of statistics as a baseline, there are about 10-12 million patients in the U.S. with osteoporosis, not to mention the over 40 million with osteopenia, low bone mass. We estimate about 3 million, about 30% of patients are treated. When we look at how they are being treated, about 50-60% of those patients we assume are on bisphosphonates, and about 20-25% are on Prolia. A minority of patients are using the anabolic drugs, which have been shown in head-to-head studies, as well as sequential studies, to be much more effective in helping a patient not progress to severe high-risk osteoporosis. When we look at the guidelines, anabolics are currently in the guidelines as frontline for imminent risk or very high-risk patients, and as second line for patients that are intolerant or refractory to other osteoporosis drugs. What we're trying to do with EB613 is really intercept the treatment paradigm and enable a viable anabolic treatment in a tablet form to support earlier intervention of postmenopausal women with high-risk osteoporosis. We believe that EB613 actually can address 40%, not less than 10% of existing patients. Just quickly through the anabolic agents, these are highly, highly effective drugs. Our thesis for this, what we call the treatment chasm in osteoporosis, is not necessarily data-driven. It is simply a silent disease where, in contrast to other chronic, more symptomatic diseases, it is very difficult for patients to accept these daily or monthly injections. Forteo has been approved now since 2002, so going on 23 years. It is the same exact amino acid sequence that we have in the EB613 tablet treatment, very good anti-fracture data. Tymlos was approved in 2018, again, highly effective anabolic drug. Both of these require daily subcutaneous injections. Evenity, which is the last approved drug for osteoporosis treatment, was approved in 2019 as an anti-sclerostin monoclonal antibody, has probably the most robust anti-fracture data, and requires a monthly injection, which has limited its use in most patients. A quick look at our clinical background for 613. Again, our target profile for 613 is to support earlier osteoanabolic intervention in a tablet format. What we're really trying to do with 613 is get into the high-risk, not the very high-risk population. This is also the patient population that FDA has concurred that we can study with our tablet treatment. This is really to provide an anabolic boost to strengthen the skeletal microarchitecture, induce rapid BMD gains, and most likely in practice will be consolidated with an anti-resorptive agent. There are a lot of clinical studies that support that the sequence actually of providing an anabolic boost prior to an anti-resorptive agent actually has greater or better clinical outcomes than the current way that these drugs are being administered. That is our goal for 613. Quickly looking at phase one and phase two study outcomes. We have conducted a number of phase one studies with 613, and we have consistently seen a very intriguing PK profile, which basically shows a slightly higher Cmax than what you see with the daily subcutaneous injection of PTH(1-34) Forteo and a shorter duration of systemic exposure. We believe that this difference in PK profile may be inducing differences that we are seeing mechanistically in preferential targeting of osteoblasts while also suppressing osteoclast activity, which we will look at in terms of the biomarker data that we have from our phase two study. Our phase two study was published in April of 2024 at JBMR, and it was actually followed by an independent editorial in July of 2024, which spoke to the unique PK profile, which represented potentially the optimal PK profile for an anabolic agent with its short pulsatile behavior. Our phase two study was a traditional dose-ranging study looking at 0.5 milligram daily tablet to 2.5 milligram daily of EB613, looking at 50-year-old plus postmenopausal women with low bone mass or osteoporosis. This was a six-month study, placebo-controlled, with about 118 patients on 613 and about 40 patients on placebo, and both primary and secondary endpoints were met. This is a look at our primary endpoint, which basically looks at biochemical markers, so proteins that you can measure in the blood, which are mechanistically directional. They provide an idea of what the drug is doing from a mechanistic standpoint. As you can see on the left side, this is the profile of EB613, 2.5 milligram tablet. It seems to, at least at six months, and we'll continue to study this in the longer phase three study, it seems to be inducing what looks like a dual mechanism where it's both increasing P1NP, but also mildly suppressing CTX. Both inducing bone formation as well as decreasing that bone remodeling that is more prominent with injectable anabolics such as Forteo and abaloparatide. This is very interesting and optimal mechanistically, and we'll continue to look at this in the phase three, the longer 24-month phase three study. In terms of bone mineral density outcomes, which was also looked at in the phase two study, what you're seeing here in the blue boxes are the placebo-adjusted BMD increases of 613 at six months. What you're seeing in the green boxes are placebo-adjusted changes in BMD across the three main skeletal sites for Forteo, which is the daily subcutaneous PTH(1-34) Teriparatide injection. Here we are seeing some differences in that 613 tablet seems to be inducing a much quicker onset of action and greater increases at the proximal femur, specifically the femoral neck and the total hip region, at least at six months of treatment versus the injectable. We will continue to study this and look for this pattern in the longer phase three study. What is very significant about this is that based on the meta-analysis work that's been published by the SABRE group, which we'll go through in a lot of detail next, changes at the total hip are the most closely statistically associated with reduction of fracture risk at all skeletal sites, including vertebral, non-vertebral, hip, and a composite of all clinical sites. We were very happy to see these increases, very nice increases, quick increases in total hip bone mineral density with 613 treatment at six months. In terms of AE profile and safety profile, 613 is still a PTH agonist, so we are seeing mechanistically exactly the same symptoms that you would see with PTH treatment, which are vasodilators. You see symptoms of orthostatic hypotension. Most commonly, we see headache, nausea, dizziness, and these were obviated when we introduced a titrated regimen where we stopped patients on a 1.5 milligram dose and built up to 2.5 milligram dose daily. This also will be carried into the phase three program. Just in terms of the phase three, our big catalyst that we've been looking forward to is not clinical since we've completed our phase two study of 613. The main catalyst ahead of us is actually an FDA change that we're expecting to see. About 12 years ago, a public-private partnership was established between the FDA, FNIH, and later sponsors, all major companies that had conducted fracture outcome studies, including Novartis, Amgen, UCB, Pfizer, in order to find a way to propel drug development and novelty in this serious unmet need condition, which requires new therapies. The gold standard endpoint for all osteoporosis drugs to date has been a requirement of fracture outcomes. This poses both ethical limitations as well as scale limitations. In order to carry out a study, you really do need to enroll a much, much more severe population in order for a small number of them to break a bone within an 18-month or three-year timeframe. If you want to treat a more moderate risk or high risk, which is still in need of treatment, the studies generally require thousands of patients. As you may imagine, IRB boards are not excited about taking a very high-risk elderly woman or man and placing her or him on placebo for two or three years to wait for their bones to break. As I mentioned, in looking at the treatment paradigm, the last approved drug happened now close to six years ago, which was Evenity, the anti-sclerostin monoclonal antibody of Amgen. The SABRE group, which is the Study to Advance Bone Mineral Density as a Regulatory Endpoint, has been guiding to finalizing what's called its qualification process to qualify bone mineral density as a surrogate endpoint, which sponsors like Entera. We believe the first company that would avail ourselves of this endpoint for our phase three would be able to use this quantitative BMD endpoint in place of fracture. We echoed the SABRE group and the ASBMR as well press release in March of 2024 that FDA had guided to providing an update on the final determination of this qualification package within 10 months. We, along with a very small group within our therapeutic indication, are in close contact with SABRE and understand that communication with FDA is ongoing and productive. We are expecting a further update from the SABRE group later this quarter. Let me move forward with just a brief background on this endeavor from the SABRE group. This was a meta-analysis that collected 173,000 patient-by-patient data, as I mentioned, from sponsors, including major pharmaceutical companies that had undergone fracture endpoint studies across seven pharmacological classes, 53 randomized studies, and basically came to two main conclusions. Number one, measurement of total hip BMD has the highest statistical association to reduction of fracture risk across all fracture categories. The second major thing is this group actually have proposed these quantitative, what they call surrogate threshold effects, which are essentially treatment targets which a drug would have to meet based on increases in total hip bone mineral density in order to be associated with a reduction in vertebral for a 1.43% placebo-adjusted increase, non-vertebral for 2.13%, and all clinical in the case of the 2.04% STE. We have a priori designed our study to meet the SABRE quantitative total hip bone mineral density outcomes. In terms of this FDA process, I just want to remind everyone that the qualification of the endpoint is not a negotiation or discussion that is happening between Entera and the FDA. This is a discussion that's happening between the SABRE group and FDA. We are, however, conducting our own discussions with FDA in terms of the non-clinical and clinical package that we would be able to pursue in order to potentially start our phase three and also get an approvable NDA. What you're looking at here is our schema for our proposed phase three study, which is being designed on the basis of multiple discussions that we've had with FDA. We're looking at a 24-month placebo-controlled study looking at what we call the white space, which is this high-risk postmenopausal women that have sustained some fragility fracture, but no major fracture, and have low bone mineral density, and where an anabolic tablet treatment holds the potential to really deter the progression of their disease. We have, as I mentioned, a priori statistically powered our study to meet the surrogate thresholds that have been published by the SABRE group. We are awaiting this final ruling, a determination from the FDA to be able to hopefully start our study in the second half of 2025. Just very briefly on some updates that have happened in the past year with our partnership with OPCO. We have two programs in partnership with OPCO. The first program is a GLP-2 RL tablet once a day is the profile that we're looking for. This is using a long-acting GLP-2 analog that OPCO had developed as a weekly injection combined with our NTAB technology platform. What we completed in 2024 basically is the PK/PD validation and potential of a single tablet GLP-2 to potentially be used as a clinical candidate for patients suffering from short bowel syndrome and other mucosal inflammatory GI disorders. This is on the heels of our May 2023 manuscripts where we showed that, and we're the first group to show a specific gastric stomach absorption of GLP-2 using teduglutide, which is the only approved GLP-2 treatment. There are two investigational long-acting injections in phase three and pre-NDA in the hands of Zealand Pharma and Ironwood. We were very happy to see the outcome of this PK/PD across two rodent and large animal minipig models, which showed prolonged systemic exposure and target plasma levels that appeared to be suitable for a once-daily GLP-2 tablet administration. We also saw a very nice pharmacological effect of the oral GLP-2, and we're presently looking to move this towards IND enabling studies. We think that the tablet has a very nice opportunity to come into short bowel syndrome given the heterogeneity of the patient population in terms of the patient having very different characteristics and the number of days that they're on TPN. This could be a very nice way to titrate or manage patients or place patients on maintenance therapy, really providing them a much more simple way to manage that disease potentially. The Exintemodulin program uses an Exintemodulin analog that had been originally developed by OPCO as a weekly, excuse me, long-acting injectable drug candidate. That candidate actually went through phase two studies in 110-odd patients with obesity, high BMI, and showed very nice kind of weight loss. Also, because of the glucagon targeting, showed a nice cardioprotective profile. We have since changed the profile of this Exintemodulin analog to maintain its long-acting PK, but also enable us potentially to really go up, increase the dosing, go up the dose curve, which was not possible using the previous once-weekly injectable. What we have completed with OPCO in 2024, again, is a PK/PD validation in animal models. Again, what we are seeing is significant systemic exposure across these two models, the target plasma concentrations achieved, and duration of exposure consistent with the half-life of the only approved oral tablet of any peptide, which is Rybelsus, Novo Nordisk's GLP-1 analog. We also showed statistically significant reduction in early PD models, looking at plasma glucose levels in rats. This program, also, we are looking to move into an IND enabling track in partnership with OPCO. Very briefly, and in the interest of time, we are planning to continue to program 613's phase three initiation to commence in the second half of 2025. We are expecting an update from the SABRE group this quarter. Just to clarify, we do continue to believe that, according to our current plan, which was always to start the study in the second half of 2025, as long as we receive news from the SABRE group and FDA on this ruling in the beginning, let's call it Q1, up to a little bit past Q1 of 2025, we're not going to change our goal and ability to start this study as planned in the second half of 2025. In terms of 612, which is our undisclosed collaboration, we also hope to be able to disclose more information on that in this quarter, if not the first half of 2025. As I mentioned, with the two OPCO programs, we're presently planning to move both the Exintemodulin as well as the GLP-2 into IND enabling stages. Thank you very much. I see that I'm out of time. Great. That was a very, very comprehensive overview, Miranda. Thank you very much. I think we have no time for questions. Again, that was highly informative. I guess my one question, if we can fit it in quickly, is before we hear the final update from the SABRE FDA discussions on BMD, will there be any interim news flow or is it going to be basically that decision will be announced at some point, hopefully soon? Interim news flow from Entera or from the SABRE group? No, from the SABRE group. I'm not sure what the communication plan is. We are in communication with the SABRE group. I would imagine that the next piece of news coming out of them is an update on the determination of the endpoint. Okay. Yeah, we're all looking forward to that. Thank you again. And thanks to everybody who tuned into this session with Entera Bio. Take care. Thank you, Leland. Thanks a lot. Thanks.