Hello everyone, and thank you for joining the H.C. Wainwright 27th Annual Global Investment Conference. My name is Sara Nik , and I'm a VP of Equity Research here at H.C. Wainwright. It's my pleasure to introduce our next speaker, Miranda Toledano, CEO of Entera Bio , a biopharmaceutical company developing first-in-class oral therapies to address unmet medical needs. On behalf of H.C. Wainwright, Miranda, the floor is yours.
Thank you so much, Sara, and thank you again for the opportunity to partake in the conference. I'll be making some forward-looking statements, so I encourage everyone to review our SEC filings. Entera is a company that really has a mission to develop first-in-class oral peptide s to empower patients and unlock clinician access. We leverage a proprietary technology platform we call N-Tab f or Entera Tablets, which essentially enables us to develop pure peptides in a simple tablet format. Our lead asset, we call EB613, is currently the only oral peptide in development for osteoporosis, and we'll be spending quite a lot of time on EB613 as we go forward. We also have pipeline assets in hypoparathyroidism, metabolic and obesity, and GI inflammation. Our cash runway is into Q3 2026, and we are listed on NASDAQ under the symbol ENTX.
This is a quick look at what our technology platform, N-Tab, tries to do. As many of you know, the challenge of developing peptides in a tablet format is due to three main reasons. One of them is the proteolytic activity within the stomach and the intestine that breaks down anything that we ingest. The second is the polarity of these molecules, which we focus on large linear hydrophilic peptides with a molecular weight of greater than 4 kDa. The size of these molecules just does not enable them to get through paracellularly, in contrast to smaller proteins such as cyclic proteins.
What N-Tab technology platform attempts to do is both inhibit this enzymatic degradation in the GI tract using specific excipients that are really specified to each peptide that we're working with, as well as in combined SNAC, which is a transcellular permeation enhancer, which enables epithelial permeability for the tablet to get into systemic absorption. This is a quick look at our pipeline, and each of these candidates is an oral peptide, and each of these candidates has a different backbone that is specific to the nuances of each molecule. EB613 is our lead clinical candidate. This is the first and PTH(1-34) teriparatide tablet treatment, and we're looking to move EB613 into a double-blind, placebo-controlled phase III registrational study. We have different PTH(1-34) teriparatide program, which is specifically looking to a PTH(1-34) teriparatide directed protein replacement therapy for patients with hypoparathyroidism.
We also have a partnership with OPKO , looking at the development of a proprietary oxyntomodulin or dual GLP-1/glucagon agonist in tablet format. That program is subject to a license and collaboration agreement, which we inked in March of 2025. We are aiming to move this first-in-class GLP-1/glucagon tablet into the clinic, filing an IND expected early 2026. EB613 is the first once-daily anabolic or bone-forming agent for the treatment of osteoporosis. We know from multiple clinical studies over the years, there is substantial evidence, and it is also within clinical guidelines, that the efficacy of anabolic or bone-forming therapies is superior to bisphosphonates for lowering the fracture risk of osteoporosis patients. However, all available anabolic agents are administered by subcutaneous injection, which has greatly limited both clinician and patient access.
EB613 has the exact same amino acid sequence as Forteo, which was approved 23 years ago by Lilly and is a daily subcutaneous injection containing the 34 amino acid sequence of the parathyroid hormone. The mechanism that we're proposing for EB613 that we've seen in clinical studies is that we seem to be seeing a dual mechanism, which both stimulates new bone formation and suppresses bone resorption. Our thesis for EB613 is we aim to provide a validated mechanism of action, osteoanabolic in tablet format, to support early intervention in the patient journey to strengthen bone and skeletal microarchitecture, and most likely will be followed by an antiresorptive agent. Osteoporosis is a disease where the healthy bone remodeling cycle is disrupted. From the minute we're born until we die, our bones are constantly being degraded and being rebuilt.
In osteoporosis, the rate of bone degradation or bone resorption outpaces bone formation. This is a disease that afflicts more women than heart attack, breast cancer, and stroke combined. About 200 million women across major geographies are afflicted by osteoporosis. One in two women over the age of 50 will break a bone due to osteoporosis. Less than 25% of women receive adequate medication within six months of a fracture. This is a lethal disease where 20% of adults that sustain a hip fracture die within 12 months. If they do not receive surgical intervention, 60% of hip fracture patients die within six months. Each fracture leads to an exponential risk of the next fracture and more perilous fractures. It really is important to try to decrease the risk of fracture early on in a patient's journey. This is a look at the current treatment osteoporosis paradigm.
On the left side are the antiresorptive drugs in the gray box, where these are the drugs that basically, their mechanism of action looks to decrease the bone of degradation. However, they are not bone-forming drugs. The most commonly used are the bisphosphonates. We estimate there are about 10 to 12 million patients prevalent in the U.S. with osteoporosis. About 1/3 of those, between 25% and 1/3 of those, are actually treated. Bisphosphonates really control the lion's share of prescriptions. About 60% of patients take bisphosphonates. These are orally available and also can be taken as a once-a-year injection. The second most commonly used drug is Amgen's anti-RANKL monoclonal antibody. Very great, very good efficacy. Also, much easier for a patient to accept in a silent disease, as it only requires an injection once every six months.
Once a patient has become refractory or resistant to an antiresorptive or is ineligible for an antiresorptive drug, they are, by the guidelines, recommended to get onto an anabolic drug. Those are the blue boxes on the right side of the slide. There are three approved anabolic drugs. The first to be approved was Forteo 23 years ago, which is teriparatide and requires a daily injection. The second approval happened in 2018 with Radius 's Tymlos, abaloparatide, and also requires a daily subcutaneous injection. The third and last drug to be approved in osteoporosis happened six years ago in 2019, which was r omosozumab EVENITY, an anti-sclerostin monoclonal antibody. These are all highly efficacious drugs and nonetheless are estimated to treat less than 15% of patients. Our mission with EB613 is to provide a known mechanism of action in a daily tablet treatment.
Our intention is to widen both patient and clinician access. This is a disease that is treated by various healthcare providers in the ecosystem, including primary care, gynecologists, endocrinologists, and rheumatologists. Most patients are being treated in the community and by gynecologists. This is a woman-centric disease, and baseline BMD measurements are quite frequently taken as a woman transitions through menopause and estrogen levels start to decrease. Most of these primary care and gynecologists do not even have in-office resources or billing systems to administer these subcutaneous injectable anabolic drugs. We believe that's another reason why access is decreased. This is a look at the PK profile for EB613, which has been quite consistent across our phase one studies. As you may know, brief intermittent exposure to PTH at high concentrations stimulates bone formation.
EB613's PK profile is really characterized by a rapid increase in PTH(1-34) levels, same Tmax, so time to peak concentrations within 20 minutes as Forteo. EB613 has a much, much more rapid elimination phase, and overall its duration of systemic exposure is shortened but not of injectable teriparatide. We conducted a phase two dose-ranging placebo-controlled study, which was in postmenopausal women with osteoporosis, 161 patients, 118 non-active, looking at doses of EB613 from 0.5 mg - 2.5 mg, both titrated and non-titrated. The primary endpoints were biochemical markers of bone formation. We also looked at bone mineral density across each of the skeletal sites at six months. This is a look at our primary endpoint, which was looking at these proteins you can measure in the blood, which are markers of bone formation, P1NP, and bone resorption, CTx.
What was interesting, at least with six months of treatment of EB613, is we seem to be seeing a favorable bone modeling profile, which increases markers of bone formation while mildly suppressing CTx, which is a marker of bone resorption, indicating an anabolic effect with a dual mechanism, which is not typical with subcutaneous teriparatide, which increases sharply P1NP, but also increases bone resorption. This is a look at the BMD outcomes. EB613 increased bone mineral density at each skeletal site at six months. Our study, again, was a placebo-controlled study. The blue boxes on the left of the gray lines are showing 2.5 mg dose. That's our top dose. That is our clinical dose of EB613, both titrated and fixed dose. This is published data for Forteo in a six-month, very similar baseline population, phase two study. One thing I would mention is there were two different dosing regimens.
2.5 mg, the titrated regimen, patients got 2.5 mg of 613 only for four months out of the six months of the study, and the non-titrated received full 2.5 mg for the full six months of the study. The takeaway message from this slide is that we seem to be seeing pretty similar increases with spine or trabecular bone increases with 613, but we have a much faster onset of action and greater increases at the proximal femur region. Specifically, we're seeing these very nice increases at the hip. This is critical as a meta-analysis that was conducted by the SABRE Group demonstrated that increases of bone mineral density at the hip have the highest predictive value to determining fracture risk reduction at any skeletal site. We also conducted an analysis using 3D Shaper software, which basically looks at the trabecular and cortical bone compartments.
This was in addition to the 2D- DXA BMD outcomes that I just showed you. What we see from this analysis is that EB613 on the right side shows again consistently an early effect on both trabecular and cortical bone. We believe this may be attributed to its dual mechanism of action, which is both increasing formation and decreasing resorption in the short term. A comparable assessment with Forteo, which was conducted in the Miller and the abaloparatide phase III study, actually showed minimal effect on cortical bone for teriparatide at six months. In terms of AE profile, we are a PTH agonist, and this is the same amino acid sequence as Forteo. Our AEs are similar to that reported for Forteo and other PTH agonists. These are symptoms of orthostasis, most commonly headache, nausea, and dizziness. We do plan to move the titrated regimen into phase III testing.
This was very well tolerated by patients, and there were no serious AEs related to EB613 in the phase 2 study. This is a look at the phase III registrational design, which we recently announced that we have agreement or alignment with the FDA to conduct a double-blind, placebo-controlled, 24-month single phase III registrational study in postmenopausal women with osteoporosis, using the primary endpoint of total hip bone mineral density or BMD from baseline to 24 months. This was an unprecedented agreement that we're very proud of. As you know, bone mineral density has been the diagnostic patient stratification and disease management metric really since 1986. However, pivotal studies using BMD have in the past required active control or the drug to have been previously approved based on a fracture outcome study.
This type A announcement that we recently announced at the end of July enables us to move forward with our study as planned, using total hip BMD as our primary endpoint. Our secondary endpoints that we will be examining include a demonstration of a positive trend on reduction of new or worsening vertebral fractures. We also will be prospectively assessing the published surrogate threshold effects that have been put out by the SABRE team, which are associated with vertebral or clinical risk and nonvertebral fracture outcomes based on increases in total hip bone mineral density. We also will be looking at percentage change in bone mineral density at 6, 12, 18, and 24 months, as well as safety endpoints. We conducted various patient and healthcare ecosystem clinician surveys in the last six months to a year.
We are seeing trends that are consistently highlighting the need for more effective solutions in osteoporosis. With clinicians that we surveyed, spanning gynecologists, primary care, endocrinology, and rheumatologists, 30% of osteoporosis patients, even in light of existing treatment, receive suboptimal responses to the drugs that they are taking. We believe that those are both due to compliance and access. We also are seeing very positive prescriber confidence in terms of enthusiasm to prescribe EB613. This really is across, again, gynecologists, primary care, endocrinologists, and rheumatologists. We did conduct several patient surveys, and again, very positive reception. 55% of patients appeared to be interested in oral bone-building treatments, and 37% of patients discontinued treatment due to side effects. We believe that based on the profile for EB613, we may also have significant price advantages versus the injectable anabolic drugs on the market today.
This is a quick look at the data that we put out at the endocrinology meeting in June of 2025 for the dual GLP-1/glucagon agonist, which we are developing as a single daily tablet in partnership with OPKO . The PK profile that we're seeing with this candidate really is showing a duration of exposure, which is consistent with the reported half-life for semaglutide RYBELSUS, which is the only approved oral GLP-1 peptide analog. We also showed good preclinical PD response with reduction in plasma glucose levels compared with placebo in rats. The PK profile that we're generating appears suitable for, as I mentioned, a once-a-day tablet. We are aiming to file an IND for oral OXM in early 2026. This is a summary of the PK-PD results that we also generated in a research collaboration with OPKO .
This is a development looking at a proposed oral GLP-2 tablet specifically designed for patients with short bowel syndrome and other GLP-2 mediated conditions. We had previously done work at Entera with teduglutide, which is the only approved GLP-2 analog. The plasma half-life with the oral GLP-2 that we worked on with OPKO was found to be about 6x - 15 x longer than the half-life of teduglutide, with prolonged systemic exposure and target plasma levels that we were looking to achieve, at least in large animal models. This program is under strategic review.
Looking forward to the tail end of 2025, we are moving forward with planning our phase III study based on the concurrence that we received with the FDA, which we announced in July on the finalization of a Type A meeting and agreement for EB613 to use total hip BMD as the primary endpoint. We are planning to present supplemental data at the American Society for Bone Mineral Research in early September for both EB613 and a next-generation candidate of EB613. We are also working on the hypoparathyroidism program, validating preclinically a different peptide, and hope to have data on that at the tail end of 2025. We are also planning to file an IND for oral GLP-1/glucagon OXM with OPKO in the beginning of 2026. With that, I'll pause and thank you very much.
Thank you so much, Miranda and Entera , for a very informative presentation. We appreciate the time and effort that went into preparing this. Thank you again from the H.C. Wainwright team.
Thank you so much for having us.