Entera Bio Ltd. Ordinary Shares Canaccord Genuity's 46th Annual Growth Conference

Thanks for being here. Thank you so much for having me.

Thank you. So Entera leverages on our N-Tab platform, which stands for Entera Tablets. Basically, what that enables us to do is develop simple tablet formats of native peptides, which really is a huge technological challenge, and that's due to three main reasons. Peptides, even though they're the smallest of proteins, are still large molecules, and we specifically focus our efforts on large hydrophilic linear peptides like PTH, GLP-1, GLP-2, and the like. They have polarity limitations, which even if stabilized in the GI tract, do not enable them to permeate into the bloodstream for systemic absorption and bioavailability. Of course, the proteolytic environment in the gastrointestinal tract readily degrades anything we ingest. What N-Tab does is it has two main mechanisms of action.

One of them is to stabilize the peptide, and we use specific excipients to deactivate proteolytic enzymes in the stomach and the intestines, such as pepsin and chymotrypsin and trypsin locally around the tablet. Our tablets are not encapsulated. They look like an off-white, white baby aspirin size. The second mode of action is we use SNAC, which is a transcellular permeation enhancer, which basically increases epithelial cell permeability so that once the peptide is stabilized, goes through the GI tract, can enter the bloodstream at therapeutically relevant levels. I would just mention that every candidate in the Entera pipeline is a pure peptide.

What we are talking about is pure amino acid sequences. This is not a medicinal chemistry approach. This is really just the pure kind of native peptides. The only modification, and this is not in relation to EB613, but in relation to our other pipeline, is in certain situations where we need to, for example, seek a specific PK profile, which requires us to extend the half-life of that sequence, then we will acylate. Quite similar to what Novo Nordisk has with semaglutide, which is an acylated GLP-1, and of course, is marketed as both Ozempic and Wegovy tablets today for diabetes and obesity.

Okay. The And osteoporosis osteoporosis.

Osteoporosis specifically, teriparatide, which is the API in EB613, which is our lead clinical candidate, which we plan to move into phase III imminently, pursuant to our alignment with FDA, which we announced on June 22, 2026. Teriparatide is a 34 amino acid sequence of the parathyroid hormone. It's the functional region of the native peptide. It's a very short acting analog. It has a half-life in blood of about 5, 6 minutes. And it has the ideal profile to engender, in an unmodified way, bone formation and an anabolic effect. If you're looking to engender bone formation, which is the mode of action of EB613, what you're really looking to do is produce a very short pulsatile PK and kind of get that osteoblast, osteoclast mechanism going, and of course, induce rapid gains in bone mass and bone strength.

Entera, our scientific capabilities are in developing the oral peptide, so it was quite reasonable almost a decade ago when this labor of love began to focus on a native peptide that had, with no modification, the correct PK for osteoporosis. If you look across our pipeline, the rest of the candidates are acylated, and their half-life has been increased to basically provide a protein replacement therapy for EB612 for hypoparathyroidism and to provide a long-acting peptide for metabolic syndrome. Osteoporosis as a therapeutic indication, though more importantly, is the most common metabolic bone disease globally. It is also probably the most under-treated yet diagnosed chronic progressive disease. There is a persistent treatment chasm in osteoporosis, and that doesn't necessarily stem from lack of available treatments.

But there are certain limitations to current treatments and an enormous challenge in relation to the three anabolic or bone-forming treatments for osteoporosis, which consists of FORTEO, a daily subcutaneous injection, abaloparatide-Tymlos, daily subcutaneous injection, and Evenity, an anti-sclerostin monoclonal antibody. Patient acceptance of these when they start to progress is quite limited. And so what we're trying to do with EB613 is really democratize anabolic therapy and develop a viable anabolic in a tablet, really so we can address patients across the clinical ecosystem for osteoporosis, which really range from primary care, gynecology, endocrinology, rheumatology, and orthopedic surgery.

So in relation to question one, we were at FDA every year since the end-of-phase-II meeting.