Entera Bio Ltd. Aktie

Good morning everyone and thank you for joining us. My name is Yehuda Leibler from Entera's Investor Relations team and I'll be hosting today's discussion on behalf of the company. Today's event will focus on the osteoporosis treatment landscape and the clinical perspective on Entera's lead clinical candidate, EB613, an oral PTH (1-34) tablet.

Joining us today, we have Miranda Toledano, the Chief Executive Officer of Entera; Dr. Felicia Cosman, Professor of Medicine at Columbia University and a globally recognized authority in osteoporosis and anabolic therapies; and Dr. Steven Goldstein, Professor of Obstetrics and Gynecology at New York University Grossman School of Medicine and a former President of both the International Menopause Society and the North American Menopause Society.

Before we begin, I'd like to remind our audience that today's discussion may include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding Entera Bio's clinical development programs, development plans and the potential therapeutic and commercial profile of EB613. These statements are subject to risks and uncertainties that could cause actual results to differ materially. For a full discussion of these risks, we refer you to Entera Bio's filings with the U.S Securities and Exchange Commission.

In addition, today's discussion will include perspectives from participating physicians based on their clinical and research experience. These views are their own and do not constitute medical advice or regulatory guidance.

With that, I'll turn it over to Miranda for some opening words.

Thank you, Yehuda, and welcome, everyone, to this roundtable discussion. Today where we are looking to put a spotlight on the treatment of osteoporosis and specifically on the opportunity for our lead clinical candidate, EB613, which is being developed as the first and only anabolic or bone-forming tablet for patients with osteoporosis.

For those of you less familiar with Entera, we are a biotechnology company that leverages on a proprietary platform that enables us to develop tablet or pill formats of peptides, and peptides are simply small therapeutic proteins. Our platform and science is focused on large linear hydrophilic peptides specifically, and we have programs across PTH, GLP1/glucagon, for metabolic and fibrotic diseases, GLP-2 for mucosal diseases of the gastrointestinal tract, such as short bowel syndrome, and we also have a separate Long-Acting PTH program looking to provide a protein replacement therapy to patients with hypoparathyroidism.

Specifically, all of those pipeline programs are in preclinical development, and we expect to move the Long-Acting PTH for hypoparathyroidism and potentially the GLP-1/glucagon metabolic program into clinic in potentially 2027.

Our mission with EB613 is really to provide potentially millions of women and men an opportunity to adequately protect their bone health. Osteoporosis to date has limitations in terms of the uptake, accessibility and acceptability of the available anabolics, all 3 of which require either daily injections or a monthly injection at the clinician's office. And so our goal with EB613 is actually to turn that equation on its head and democratize anabolic therapy so that with a simple tablet format, with a well-known mechanism of action, we can actually provide an adequate anabolic to millions of patients to the majority of patients that are eligible for this type of treatment.

So without further ado, we have kind of set this up as a roundtable discussion with Dr. Felicia Cosman and Dr. Steven Goldstein. We're very privileged at Entera to have both of these key opinion leaders as our endocrinology and gynecology gurus. And their perspective is really important in terms of our understanding or gaining understanding of the clinician voice, but more important and as important in our thesis is really the patient place.

So thank you so much, and I'll turn it over to Yehuda.

I think what we want to do now is move into a discussion around how osteoporosis is managed in practice today, where the key gaps exist and maybe how the field will evolve over time.

And so I thought maybe we could start by giving our audience some context about the current treatment paradigm. From your perspective, Dr. Goldstein and Dr. Cosman, across clinical practice, research leadership, do you think there's still a meaningful treatment gap in osteoporosis today? And what, in your view, are the primary drivers of such a gap? And maybe we'll start with you, Dr. Goldstein, as a key opinion leader in gynecology, it would be great to hear your thoughts on this.

Well, thank you, and thank you for having me. OB/GYNs, well, at least here in the United States, really function as the primary care physician for bone health for our female patients who are going through the menopause transition and have arrived in menopause. We did a survey of a large group of doctors, gynecologists recently. And I want to share with you some of the findings because they're really eye-opening. 92% were ordering DXA scans. 71% would treat patients to prevent osteoporosis. 82% were familiar with the FRAX model. 64%, were treating patients with osteoporosis.

And when we ask them what drugs they used, more than 90% would utilize alendronate, known as Fosamax. More than 60% used risedronate, Actonel. Slightly more than 50% would use raloxifene, Evista. And slightly more than 50% were using denosumab as well, Prolia. But notice all of these are anti-resorptives. When it came to the anabolic agents, the injectables, only 12% of the gynecologist surveyed were using any injectables, yet 92% of them said they would treat if an oral anabolic agent were available to use. It was interesting that even 50% of those who don't currently treat said that they would consider treating if an oral anabolic were available. So clearly, there's a gap.

And the other place that, that gap exists is when patients do become severe enough now to need or want an anabolic agent, gynecologists, by and large, are referring them either to the endocrinologists or rheumatologists. And that step of having to refer is one more place where they can fall through the cracks, where they often don't end up in that endocrine or rheumatology office, or they have difficulty making the appointment. It's just -- or they don't want to have an injectable to start with even if they do get there.

So there's a tremendous disconnect here that I think this oral agent would fill that space.

I agree with everything that Steve said and the proof of this is that we've got about 2 million fractures occurring every year due to osteoporosis at least in part. And those fractures have consequences on both quality of life and on mortality. And our ultimate goal is to try to present these and to improve both quality of life and longevity.

To jump in and just increase on what Felicia just said, some of the statistics are eye-opening, and I go over this with all of my patients. Do you realize that in the United States, the survival in Stage 1 breast cancer is 99%. And most of my patients are really cognizant of their breast health. I mean they go for their mammograms religiously annually, they're scared to death of breast cancer. But when I tell them that in this country, if a woman fractures a hip, 21% are dead within a year, 25% can end up in a nursing home.

Yes, sure, they may be a little bit older, but it said that a 50-year-old woman who doesn't already have cancer or heart disease has a life expectancy of 91. Women are living so much longer than they did a generation or 2 ago. That bone health and fracture prevention in my mind, may be just as important, in fact, if not more important than breast health, especially if you are diligent about your breast imaging because Stage 1 breast cancer is not the disease it was when some of us were growing up, but fractures are a huge, huge burden both on financially, morbidity and even mortality.

What we've done is really try to survey and understand who are the players and who are -- who's taking of osteoporosis and where do patients seek health. And this is such a widely dispersed clinical indication, it is synonymous with endocrinology and rheumatology, but it is really being treated at the gynecologists' office, at primary care as well as at the specialist office. And I would dare to say that the vast majority of patients are not being treated at the specialist office or don't make it there.

I think the other thing that we've noticed doing clinician surveys and kind of look at prescription trends is that, this is a conservative group. But the prescriptions are quite consistent across each of the key stakeholders. And we kind of see this globally. We've discussed this with Asian clinicians, and we've discussed this with clinicians across Europe. And the vast majority of women are being treated with bisphosphonates. And this was always the case even when Fosamax was not generic.

And I think there's something to be said for silent asymptomatic disease that when a woman understands that she has low bone mineral density. And consistent with that, her skeleton, is deteriorating the go-to in a silent disease while she may not have fractured yet, but it's clearly high risk and should be on anabolic is to agree to get on to an oral agent. And most likely, those women, we know statistically stop taking bisphosphonates because of acid reflux and other side effects. And that's something that we're trying to close that gap as well.

So I think what we need to talk about is education and empowering women to protect their bone health, but also providing something that they when looking across to their clinician may actually accept to take. At least that's our goal at Entera for EB613 to kind of change the conversation. So a woman and hopefully, man will be able to protect their bone health and feel comfortable. And I think part of our thesis also with EB613 is that we're not looking to reinvent the wheel. We're trying to provide a tablet, a drug that's been approved for 24 years, that has a very well-characterized efficacy and safety data set and also sequence data, and we'll get into that a bit more.

And so we've all touched on this at this point, anabolic therapies. Specifically, I think it would be good to give some context on how these are different from anti-resorptive treatments and kind of what role they play in managing osteoporosis today. I also think it would kind of be good to understand a little bit about how they are used in clinical practice and maybe where adoption sits, barriers sequencing as part of the broader treatment pathway.

Sure. So anabolic treatments actually stimulate the growth of bone tissue. In contrast to anti-resorptives, which work primarily by slowing bone loss that's associated with bone remodeling, a process that goes on throughout our lives, but it's accelerated after menopause. Anabolic medication produces larger and faster increases in bone density, and it can repair the microstructural defects in bone tissue. That also contribute to fragility or risk of fracture in patients with osteoporosis.

The anabolic agents that we currently have available are very effective. But we have to either inject them daily or monthly. And the need to inject to go to a specific center to get this done for one of the medications, romosozumab, where they need to teach patients how to do this on their own every day. These are significant barriers to the use of these medications by many health care providers as well as by patients. And that's one of the reasons that we have such a big treatment gap in this group of individuals.

Certainly, in clinical medicine, we are seeing a shift in the paradigm for decades. We have treated people with -- initially with anti-resorptives to try to maintain their bone mass. And if they become severe enough, then we switch them to an anabolic. Now that we understand that a significant amount of bone is lost during the perimenopausal transition into menopause. And this is especially true for many women who never peaked their bone mass in their 30s where they should have. The concept of using an anabolic first to build bone back, build bone and then switching to the anti-resorptive to maintain the gain is sort of catching on, and I think will only become more and more utilized in the future. There's a total shift here in the thinking and the paradigm and I just see it increasing as time goes forward.

Well, we know that a history of fracture is the dominant predictor of more fracture risk. And all patients who've had a fracture need to be evaluated for osteoporosis and almost always need to be treated. In patients who haven't yet had a fracture, the bone density expressed as a T-score is the dominant predictor of future fracture risk. And for these patients diagnosed either way, high or very high-risk patients, we prefer to use the more potent therapies such as anabolic treatments rather than just anti-resorptive therapies that prevent further deterioration.

Right. I think that kind of brings us perfectly to talk a little bit about EB613. So given that, based on everything you've said, the effective therapies, they essentially exist, but they're not widely enough used. Where do you see the opportunity for something like EB613? Or in other words, how would an oral anabolic be different in terms of access and usability? And where could that also fit into the patient treatment paradigm that we talked about?

And maybe we'll start off with you for this one, Dr. Cosman.

Well, we've always known that the best approach to treat osteoporosis is to try to repair the underlying bone defects. And this is best done using anabolic therapy. This concept though has been very difficult to implement with the availability only of anabolic agents. And an oral anabolic, EB613, would make it so much easier for doctors to prescribe anabolic therapy and for patients to take bone-building therapy. And we think this could have a big impact. on the treatment gap in osteoporosis.

And Yehuda, I would just repeat what I said in the beginning. I mean, these statistics speak for themselves. 12% only of gynecologists are using any injectables and all the anabolics right now are injectable. 92% said if they had an oral agent, they would utilize it. I mean that's a huge jump. And it also would negate the necessity right now that exists for referral to a specialist in endocrinology or rheumatology to get that anabolic which the majority of patients, even if they were willing to accept an injectable and many, many, many are not fall through the cracks have difficulty making that appointment. It's just one more barrier to -- if that creates that much more of the gap.

The recent feasibility study that we conducted with over 400 potential investigators across 22 countries, which included endocrinologists and gynecologists and other specialist rheumatologists. And something that really resonates with them is the fact that they know Forteo, and they know what teriparatide is, and they've had decades of experience or worked on clinical studies with Forteo.

And so the conversation and convertibility of them having a woman across the table and explaining kind of the safety and efficacy is very different from, for example, explaining the potential safety profile of a novel drug. Who's been at the forefront of those clinical studies of anabolics is Felicia and the whole sequencing story is how do you turn the table around and get younger women to protect their bones and empower their bone health when in a silent asymptomatic disease where they don't feel their bones degrading. And you're asking them to -- at the age of 53 or 55 or 56 without having sustained a fracture, but certainly is a candidate for an anabolic drug, take a daily injection or come in for in-office visits every month. I mean, what's been your experience with that?

Well, I think the concept of treatment sequencing with an anabolic first approach is one that's evolved over the last 2 decades in part because we see how much more effective the anabolic agents are when you give them as initial therapy. And the idea is to try to diagnose a woman with osteoporosis and then fix the osteoporosis, try to get her out of the osteoporosis range, achieving a BMD level that is associated with minimal or modest risk of future fracture and building up the bone structure in addition to the mass.

And then sequencing her to a treatment that will help maintain that. And there are a variety of different options that can be utilized. And this approach can help prevent many of the fractures that are otherwise occurring because we're not being proactive about treating patients when they're diagnosed with osteoporosis.

I think now it is the perfect time to maybe talk a little bit about EB613 data. So Dr. Cosman, from a clinical standpoint, when you look at EB613's Phase II data. How do you see it in the context of what you would expect from therapies in this class?

Well, our Phase II data show several really important things. First, EB613 stimulates bone formation. So it's anabolic. That's really the definition of anabolic. And at the same time, it suppresses bone breakdown. So it illustrates a dual mechanism of action at the tissue level. And the bone density increments that we've seen at 6 months in the Phase II study are comparable to the BMD increments that we see with injectable PTH at both hip and spine sites. And we know how effective this early BMD change is at improving bone strength and reducing fracture risk quickly.

Now zooming out a little, how do you look at the broader pipeline in osteoporosis evolving? So for example, what are the other approaches that you're both watching? And how would something like EB613 be positioned in that landscape? And maybe for this one, we'll start with you, Dr. Goldstein, kind of looking at the broader pipeline, what are your views on that?

Well, Felicia already alluded to the fact that it's sometimes difficult to get women who are early in the menopausal transition to take any medication for a silent disease. And what is in my practice been the motivating factor has been a T-score on their DXA scan that scares them. And whether that's not even yet osteoporotic, if they've got a FRAX number that's scary, these patients sort of wake up and want to do something about it.

The ability to build bone with an anabolic agent that also has some anti-resorptive properties like EB613 would be much more acceptable to most of my patients in that younger previously silent group who are now becoming much more attuned to bone and bone health. The National Osteoporosis Foundation, a 43-year-old support group 4 years ago, changed its name to BHOF, Bone Health and Osteoporosis Foundation. And I think that the public awareness of bone health being a huge issue as the population ages is just taking off geometrically and we'll do so more and more as we go forward.

Great. And Dr. Cosman, I know you already touched on this a little bit earlier, but is there anything you want to add before we move on?

Yes. I mean, I wanted to say that there are some new osteoporosis medications that are currently in development, and I'm very excited about these. Some of these products are going to target the very highest risk patients, patients with recent major fractures or multiple fractures or extremely low BMD. And there's a huge need for these additional therapies to come out.

But our hope for EB613 is different. With EB613, we want to approach as Steve has said and I've said and Miranda, this broader category of patients who have osteoporosis but are not yet that severe, maybe they've had a minor fracture or more remote fracture, T-scores that are in the osteoporosis range but not terribly, terribly low. And including younger patients that are offered not -- often offered -- not offered anabolic therapy. We'd like to offer EB613 to this much broader group of patients as an easy quick fix to rapidly improve BMD restore structure and reduce fracture risk and improve associated quality of life.

So, I think now maybe it's a good chance to look a little bit ahead and talk a little bit about EB613 and what you think it would need to demonstrate in order to gain acceptance amongst all these clinicians and patients?

Well, I think that the acceptance of EB613 is going to be pretty easy because this is something that many physicians are used to prescribing and patients are taking, and it doesn't require as much bureaucracy and cost and effort to get patients on a single daily pill versus an injectable therapy. So it's going to bypass a lot of the resistance that we have seen with the current agents that are out there.

We know that all anabolic therapies need to be followed by use of an anti-resorptive drug. If you take an anabolic agent by itself and then you don't do anything afterwards, you're going to end up losing the gains that you achieved on that medication. So we're always talking about a treatment sequence. And I think we have a number of different anti-resorptive therapies that would be appropriate after a course of EB613. But the idea is to use EB613 upfront for these patients with new diagnoses of osteoporosis to rapidly repair and reduce risk and then to maintain the benefits that we achieve with EB613.

Right. And Dr. Goldstein, now turning back to you. So can you talk a little bit about the perspective of gynecologists on what EB613 would need to show?

I couldn't agree more with what Felicia just said. I mean the paradigm until now and still among almost all of the gynecologists that I lecture to has been to start with anti-resorptives and an attempt to stave off further bone loss. And if patients get severe enough, they refer and then they're put on an anabolic. It totally makes absolute sense that those patients with low bone mass who are at risk should build back bone with an anabolic and then maintain the gain, as I said very early in this session with an anti-resorptive.

In terms of accessibility, the fact that it's oral can be administered by that same health care provider who's made the diagnosis who has a relationship with the patient who's not a super specialist and doesn't require a referral and going somewhere else on a different day. I mean from access, that's access with a capital A.

That's very, very helpful. And I think we've highlighted really well the challenges in the current treatment landscape and the potential opportunity for an oral anabolic like EB613 now. And I think this is a good point to maybe turn it back to Miranda to give us some closing words.

Yes. Thank you so much, Yehuda, and thank you so much, Felicia and Steve. I think you know our journey that we hope to kind of move forward into this Phase III program imminently is to address -- try to address this white space. And I think we've now designed this Phase III to answer a few questions, which include how does EB613 do as a monotherapy, right, for up to 24 months or 12 months? And how does it perform when used in sequence as it should be with an anti-resorptive drug.

I think our goal with this program hasn't wavered all these years, which is to try to ease patients and help provide a viable anabolic in a format that they might actually agree to take to protect their bone health and deter fractures and hopefully not get to a place where these comorbidities and potential mortality exist.

So anyway, thank you so much for your time today. Hopefully, this can be a series of roundtables that we have on different topics at Entera. And thank you so much, Yehuda for moderating this discussion. Thank you.

Thanks, Miranda, and thank you again to both of our panelists for a very thoughtful and insightful discussion, and we appreciate everyone who took the time to join us today. A recording of this event will be available shortly after the event concludes. Thank you very much.