Entera Bio Guggenheim 3rd Annual Healthcare Innovation Conference

Thank you very much, Vamil, for having me, and to your team. Entera is a company that's focused on developing first-in-class oral peptide therapeutics. We have a pipeline today which targets PTH(1-34) in two therapeutic indications, both endocrinology-focused, one very large, osteoporosis, and one rare disease, hypoparathyroidism. We also have programs in GLP-1 glucagon and GLP-2. Our lead clinical asset, we call EB613, is the first oral PTH(1-34) peptide in late-stage development for osteoporosis.

EB613 has the exact same amino acid sequence as Forteo, which has been approved by Lilly for 24 years now under the name Forteo, FORSTEO in Europe. The API is teriparatide, the functional region of the parathyroid hormone, which is a mainstay treatment for osteoporosis. EB613, because we share the exact same API as Forteo, is pursuing a 505(b)(two) application with the FDA. However, we have a very robust kind of clinical and even preclinical program for a 505(b)(two) application. We have six-month rat and nine-month non-human primate toxicology studies. We have three phase I safety and PK studies where the same participants received EB613, our tablet, or tablets, and Forteo at separate visits, and we monitor both PD, PK, and safety outcomes. Our phase II was specifically, of course, in postmenopausal women with low bone mass and osteoporosis.

That was a 161 placebo-controlled dose-ranging study where we looked at 0.5 up to 2.5 milligrams of EB613 daily, which met both biomarker as well as BMD endpoints, and that is published. Then we also have a similar formulation where we had a proof of concept phase II study in hypopara patients, which of course is a different disease, but that was dosed up to nine milligrams a day, and also makes We have it as part of our safety database.

Okay. So we have 270 subjects exposed to EB613 to date.

Where to begin? Okay. I describe osteoporosis as the most diagnosed yet undertreated chronic progressive condition globally. We're talking about 200 million women. This is a woman-centric disorder, so women are most at risk of developing osteoporosis, because estrogen declines during the menopause transition, and that creates rapid bone loss and a susceptibility to fracture. With the currently available drugs, and again, there hasn't been a new drug approved for seven years now, and there hasn't been a phase III for close to a decade, we estimate that a vast majority of patients do not have access or do not accept the currently available drugs. The currently available drugs basically fall into two main buckets. One of them are the antiresorptive drugs, and those are most commonly the bisphosphonates and PROLIA, denosumab, the anti-RANKL monoclonal antibody.

We estimate about 80% of prescriptions go towards those two sub-buckets, the vast majority bisphosphonates. Not surprisingly, this is a silent and asymptomatic condition, so it is much easier for a woman or man to agree to get onto an oral agent once diagnosed. Antiresorptive drugs do not rebuild bone, and more importantly, they do not ameliorate the skeletal microarchitecture decay that happens in osteoporosis in contrast to anabolic drugs like PTH agonists, romosozumab, the three approved injectable anabolics, and hopefully EB613. The limitations to the current anabolics, however, even though they have superior efficacy and potential disease-modifying attributes, is that they are accessible or accepted by a minority of patients for different reasons, including cost, including mode of administration, and including different access limitations.

There is a white space in osteoporosis, and the FDA itself, in its qualification of the bone mineral density endpoint, notes the need for novel agents in this severe condition.