Radius Recycling, Inc.

Ladies and gentlemen, and welcome to the Q1 2021 RADIUS Health Incorporated Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star, then zero on your touch-tone telephone. As a reminder, the conference is being recorded. I would now like to turn the conference over to your host, Mr. Ethan Holdaway, head of IR.

Thank you, and hello, everyone. Thank you for joining us today. A press release and presentation that we'll use to guide the discussion can be found in the investor relations section of our website. A replay of the call will also be available on our website three hours after the call. Before we begin, I'd like to remind everyone of our safe harbor statement on page two. This presentation includes forward-looking statements and non-GAAP financial measures. You can find the reconciliation of GAAP to non-GAAP at the end of the finance section of the presentation. Our most recently filed 10-K and subsequent filings identify factors that could cause our actual results to differ materially from those indicated by the forward-looking statements. Any forward-looking statements represent our views as of today only. On today's call, Kelly Martin, president and CEO, will start with his opening comments. Jim Tropis, our principal finance and accounting officer, will then provide a financial update. Sal Grasso, chief commercial officer, will follow with an update on the Timalos commercial business. Chaya Shah, our chief business officer, will provide a clinical and regulatory update on Ebola Paratide. And Liz Messersmith, head of our orphan business group, will finish with a brief update on RAD11. We will then open the call up for questions. I'd now like to turn it over to Kelly.

Thank you very much, Ethan, and welcome, everybody. Thanks for taking some time this morning, this Friday morning, for our Q1 update. As Ethan said, you'll hear from the leadership team on various parts of the business and With regard to RAD 011, Liz will give you a brief update on where we stand with that molecule and program in future calls. You'll also hear from Rupert Haynes, who's accountable for the franchise, as we move that forward. On page four, from an opening commentary point of view, I wanted to emphasize a couple important things. We run the company based on the assets that we have. We have three large and identified assets. Obviously, Abala Paratide, Elastostran, and now RAD011. For Abala Paratide, the SC business in the U.S. is an excellent business with high margins and a lot of upside. Sal, you'll hear more from Sal about the commercial pivot towards fracture patients. We believe that there's good upside with that business. In addition to that, there's three other areas for upside. We will obviously have the patch readout, which you'll hear from Shia on in the second half of this year. We have the mail readout, also the second half of this year. And you have an international opportunity to globalize the molecule into other markets. We've made progress in Japan and Canada, and we hope to incrementally make more I would characterize and we characterize all three of those buckets as additional upside to the asset. Elastostrand is now partnered with our good partner Menorini Group from Italy. That transaction, in my opinion, last summer was the most important thing over the last 12 months that we got accomplished. We like the space, meaning the breast cancer space. It is a crowded and sophisticated space. we do have with Menorini the lead molecule from a timeline point of view, and we would also characterize that data readout as upside to us given the transaction that we did last year, which took out the event risk for us. Last but not least, with RAD011, it was an asset that we were able to acquire at reasonable acquisition costs, It's an asset that has a multiplicity of applications, which you'll hear from Liz about briefly. Our initial focus is PragerWilly. There's activity going on in additional potential orphan indications. We view that asset as an asset that could have high optionality that would be easily absorbable from a P&L point of view. So that's the way we think about the portfolio of the current assets that we have. From a P&L point of view, we continue to focus on the operating leverage of the company. We believe there is significant operating leverage within the company. And our focus, in addition to the portfolio approach, as I described above, our focus also is resolute on the P&L, the balance sheet, and then the value drivers of both the P&L balance sheet and the portfolio as they are interlinked. More tactically for 2021, as we've said before, our areas of focus are five main ones. Grow Tymlos-US. Execute Avaloparatide with readouts in the second half of the year for both the ADAM study and the wearable study. Expand where we can and where it makes sense the Avaloparatide footprint, and lots of discussions are in flight. achieve Elastostrand Phase III readouts with our partner Menorini Group sometime in the second half of the year. And importantly, with our new asset, a FDA meeting upcoming in June, post that meeting, hopefully we'll have a path forward on a Prader-Willi protocol and pivotal trial. That will be our main focus, and then subsequently we will begin to look at Other organ diseases, that might make a lot of sense with the same molecule. So that's the way philosophically we run the company. Portfolio, asset-based, timelines, risk-reward, and how it all fits together. And just to repeat my commentary, with Abalaparatide, international, mail, and patch are all upside. SC is a business from a commercial execution point of view, which we believe has upsides. Elastostrand with our transaction of last year, we took out the downside and the event. And then positioning properly Rad 011 for high option value would be an important part of the future value consideration of the company. I hope that's helpful to all of you as we think about the company. And with that, I'm now going to turn it over to Jim Chopas, our principal finance officer, and he will walk you through the Q1 financial results. So Jim.

Thanks, Kelly. Moving on to slide six. Our Q1 results continue to demonstrate progress toward our 2021 goal of positive earnings on an adjusted EBITDA basis. Our net loss decreased from 37.7 million in Q1 2020 to 15.7 million in Q1 2021. The improvement was the result of increased total revenue, improved sales productivity, SG&A reductions, and the exit from oncology. Total revenue improved by 17% year-over-year from $48 million in 2020 to $56 million in 2021 as a result of an increase in license revenue, partially offset by a decrease in TMLOS revenue. The $11 million increase in license revenue was primarily from the approval of a paliperitide for the treatment of osteoporosis in Japan, which earned a milestone of $10 million which was settled in April. The increase in license revenue was partially offset by a decrease in TMLOS product net revenue, which was down 6% year over year. The decrease was the result of reduced unit volumes from inventory channel destocking, plus volatility in patient activity as a result of COVID-19 during 2020. There was a partial offset from an increase in net price. We continue to show strong new patient growth in Q1, which Sal Grosso will discuss later in the presentation. and reiterate our full year revenue guidance of $250 million in revenue. Research and development costs decreased by $7.4 million on a non-GAAP basis, primarily as a result of the exit from oncology and related reimbursement of costs resulting in a $10 million reduction in oncology costs. In addition, TD research and development was approximately $3 million lower due to the timing of development activities. The cost decrease was partially offset by a $5 million payment due to Epson in connection with the approval of a valoparatide in Japan, and $1.7 million of spending on a RAD 011 program, which was initiated this quarter. Selling general and administrative costs decreased by $5.3 million, or 16% on a non-GAAP basis, as a result of our efforts to reposition the selling general and administrative cost structure. Increased commercial productivity combined with the pivot to post-menopausal high-risk fracture patients, together with reductions in corporate positions, allowed us to decrease compensation costs by approximately $3.5 million and professional service fees by $2.2 million. The cost reductions provide the company with significantly improved operating leverage, which will be beneficial throughout the remainder of the year as revenue increases. Moving on to the next slide. Our improved operating leverage and the refinancing of our senior debt facility has led to reduced cash burn. Our cash burn was zero in comparison to Q4 2020. The term loan refinancing with MidCap added $13 million to our balance sheet net of expenses. With significant operating leverage and continued improvements in profitability, we believe we are positioned to grow the company without the need for dilutive capital. Moving on to the next slide. We continue to reiterate our full-year guidance of $250 million in net product revenue and $10 million in adjusted EBITDA. We believe the growth in TMLO sales combined with improved operating leverage will allow us to fully fund our strategic investments in 2021. Moving on to the next slide. Our balance sheet continues to be strong with $115 million of cash and investments. As noted in our March 3, 2021 press release, we entered into a $175 million financing transaction to create a flexible debt structure with a more balanced mix of secured and unsecured tranches by repurchasing $112 million of the 3% convertible notes due September 1, 2024, which represents approximately 37% of the outstanding 2024 notes, and eliminating 2.3 million shares of potential future dilution upon conversion of the notes. As a result, our unsecured convertible notes payable with limited prepayment options was reduced from $305 million to $193 million. Our term loan, which can be refinanced at any time, was increased by $138 million. As noted previously, the refinancing added $13 million in cash net of expenses and accrued interest to the balance sheet. Please note that we really adopted ASU 2020-06 debt effective January 1st, 2021, which simplified the accounting for our convertible notes. As a result of the adoption, amounts related to our convertible notes that were previously recorded as a component of equity were eliminated as of January 1st, 2021. Moving on to the next slide. Our gap-to-non-gap reconciliation highlights the changes in non-cash interest as a result of the adoption of ASU 2020-06, as well as the debt refinancing charges partially offset by the gain on extinguishment of debt. With that, I'd like to turn over the presentation to Sal to give an update on our commercial business.

Thank you, Jim. Good morning, everyone. On slide 12, talk a little bit about new patient starts. As we previously communicated, we have the entire organization laser focused on new patient starts on therapy. March, we ended the quarter, the first quarter strong with March. We had 1,723 new patients on therapy, which was a 14% increase versus the prior four-month averages. which led to a strong quarter-over-quarter growth where we grew 14% in new patient starts in the first quarter 21 versus the fourth quarter 20. On slide 13, two topics I'll provide further commentary on. We're very pleased to announce that on May 1st of this year, 2021, that Humana has decided to add TMLOS to the formulary of their Medicare Advantage plans. that will have an impact on approximately 5 million beneficiaries. It gives us an opportunity to have instantaneous access to patients or patients having access to Tymlos that did not previously have access through Humana Medicare Advantage. With that change, we have an increase in our coverage for Medicare Part B from 83% to 91%, and also first-line postmenopausal osteoporosis patients uh we our first line uh but those that have a history of fracture has increased from 77 to 78 we continue to focus on the patients that have fragility fracture and the hdps that treat fragility fracture that have underlying postmenopausal osteoporosis we are pleased with our progress in this shift in strategy in q1 Our new patient prescribers, 42 of the top 50 of those prescribers were either orthopedic or specialist bone accounts. And that group of 42 actually grew new patient starts 26% versus the overall growth of 14% for total prescribers. In addition, we added over 100 new bone-focused prescribers in the first quarter. Look forward to hearing your questions. I will now turn the call over to Chaya for a clinical and regulatory update.

Thank you, Sal, and good morning, everyone. I will cover, as Sal mentioned, the clinical and regulatory progress we've made to date on the BALO program. We remain totally focused on delivering our top-line results at the second half of 2021 for both Phase III trials, as Kelly mentioned, the ADAM trial to add the male indication for TMLOS, and the wearable trial to add our new transdermal system, the patch program. For the transdermal product, we have proven in a clinical trial that our drug product used in phase three is bioequivalent to our sterile drug product that is manufactured now at our final commercial facility. Due to the success of the bioequivalent trial, we now have introduced commercially equivalent sterile drug product into our phase three trial. This is all in agreement with our FDA alignment. So it's very good news for aligning the bioequivalence criteria. For our SC-TIMLOS product, we have successfully completed the formative human factor study, which now includes men as well as women, to confirm that our appropriate instruction for use and overall use of the product. We anticipate including this data into our potential male SNDA submission. With the above successful activities, we're positioning ourselves to create a high-quality regulatory submission, assuming top-line results are positive. We've also made progress in our international space. First, I think Kelly mentioned earlier that we announced that our partner, Cajun in Japan, has achieved regulatory approval for Osteoboro. This is an important first step in globalizing a bottle-pair type franchise. a big achievement, and we have an effective partnership between Radiosentation. Second, we've made progress in European filing by submitting our letter of intent in March to CHMP to target our submission to EMA in the fourth quarter of this year. Additionally, we are in discussion at various stages, early and some advanced, with multiple regions for partnership to expand the bottle parasite footprint. Overall, I think we're making good progress on all fronts with the Avalo program. And with that said, I will hand it off to Liz Messersmith, who will walk us through the RAD011 program. Liz?

Thank you. Good morning, everyone, and thanks, Chaya. So on slide 17, I just want to provide you a brief update on where the RAD11 team is working and focusing, and that is right now on the Prader-Willi syndrome program. As Kelly mentioned, we do have a Type C meeting scheduled with the FDA that is scheduled to occur on June 16th. And in that meeting, we will be presenting our clinical development plan as well as non-clinical appropriateness for the program. In preparation for that meeting, we have been incorporating feedback from key opinion leaders as well as advocacy and foundation groups into our overall development plan. Based on the feedback, we are assuming that we'll be in a good position to start our global pivotal trial in Prater-Willi in the second half of 2021. What's most exciting for us is that we've recently received approval for oral presentation at the upcoming PWSA USA conference in June, to present the previous Phase II data. That data will be presented by one of the former PIs from the Phase II study, Dr. Lynn Berg, and that will occur on June 23rd. In parallel to this activity, we have ongoing efforts to look at the orphan pipeline, the additional indications, and continuing to build up the operational base and talent of our team. As Kelly mentioned, Rupert Haynes is leading our efforts to identify our additional orphan indications that would be a natural expansion of the cannabinoid RAD11 asset. We expect to have these plans finalized in the second half of 2021. We're pleased to announce that we've hired, and recently, Venkat Goskonda, who has over 22 years of expertise in pharmaceutical science with specific emphasis in the cannabinoid area around formulations and delivery systems. We are continuing to build out a strategy for global and regional opportunities, not only for Prader-Willi, but additional indications of interest. And our supply chain and CNC progress with our partner, Bonuvia Manufacturing, as being managed by Chris Wilson to be able to ready our program and support our clinical trial initiatives in Prader-Willi by end of year. So with that, I think that is our update on Prader-Willi and where we are with the RAD11 program. And I'll turn it back over to Ethan.

Thank you, Liz and team, for all the updates. We're now going to open up the call for questions.

Ladies and gentlemen, if you have a question at this time, please press star, then the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Our first question comes from Corrine Jenkins from Goldman Sachs.

Hey, so you all talked about the mix of orthopedists and bone specialists in that top 50 prescriber base of 42. How does that compare to maybe when you started this strategy or, you know, any time point in the past year or so?

Yeah, Corinna, Kelly, thanks for the question. I'll give you a couple comments, and then Sal can give you a deeper dive. The original marketing and sales strategy for the company was really based on sort of mirroring, if you will, uh, the Forteo sales and marketing footprint, uh, which, which, you know, I think from a launch perspective in initial years was probably completely, uh, logical. Um, and as you can imagine, the Lilly, uh, sort of footprint was very dispersed and diverse, uh, and included, uh, primary care, uh, over probably overly included endocrinologists, um, And so that was the way things started. And Sal, with his team, had kind of done a pretty significant sort of hard right into making sure that we get to the bone specialists. And so that's sort of a backdrop. And maybe, Sal, you can comment to Corinne on some of the specifics.

Yeah. Hello, Corinne. Good morning. Again, just to further add, I think when we Before we saw this, we looked at our prescriber mix and we realized that we had a smattering of metabolic bone and orthopedic specialists in the top and realized that those were the most productive accounts because we knew that they saw a high flow of patients that had fragility fracture. So we definitely expanded that. And I would say that we definitely see a cycling out of some of the general med rheumatologists and endocrinologists in that top 50 and a cycling in of new orthopedic specialists. They see such high patient counts, if you turn on the new office, which isn't easy, it requires a lot of hard work, they quickly spool up in terms of new patient starts.

That's helpful. And then maybe separately, can you talk about some of the feedback you've received from KOLs and patient advocacy groups as it relates to how you're thinking about the Pritter-Willi trial design?

I'm sure that would be great. Liz, why don't you take that, obviously.

I'm sorry, Kelly, my system just cut out. Could the question be repeated?

Yes, sorry, Liz, the question from Corinne is some of the feedback and input we got from some of the KOLs with regard to the Prater-Willi indication, trial, previous learnings from other, you know, other participations, et cetera. So just some of the specific feedback we've gotten I think would be helpful.

Yeah, that's a really great question. Thank you very much. So in the KOL feedback, what we've learned is, you know, hyperphagia is absolutely one of the key criteria that patients and families and physicians are trying to manage within Prader-Willi. And that instrument around the HQCT, which is the validated instrument that is recognized by regulators, is the key instrument by which that hyperphagia is measured. Now, there are some challenges with that instrument as it has been around for a while, and there have been behavioral modifications that are implemented in the care of these patients that makes the administration of that instrument a little more difficult. So we'll be talking with the agency about a couple of questions in particular on the instrument and our thoughts on how we can still utilize that instrument in an effective way. So that's great. And then I think the other piece that we've learned from these inputs is, you know, there is a huge unmet medical need for this population. And the population overall is very interested and supportive of new therapies to address their needs. All the way from the advocacy groups to the physicians treating these families, it's just quite impressive at the level of organization. And they've all been very engaging with us to date as we get up to speed on how we advance the program.

And I would just add to that, Corinne, that from a regulatory point of view, this particular disease, certainly has the attention of the highest levels within the neurology area.

I think that's very helpful. Your next question comes from Jeffrey Porges from Lee Rink.

Thank you very much. I appreciate taking a couple of questions. First, could you remind us of the terms of your collaboration with Teishin in Japan? So, you know, how you would get paid for that and then Could you characterize the size of the opportunity there? A related question, will you partner to commercialize in Europe, and what terms would you advise us to expect? I mean, I know it's sort of open there right now. And then lastly, could you go through again the puts and takes in the reported revenue in the U.S. for Q1, just for Tim Long? You know, it sounds as though there were quite a few moving parts and adjustments there. And I'd love to know what the net price trend is and what that's going to look like for the rest of the year.

Okay, great. Thanks, Jeff. We'll turn to Sal and Jim for the third of your questions. On the first two, I'll sort of frame it out for you. The answer to your Europe question is, Yes, absolutely. We would partner the asset out. This is obviously for the SE product. On the heels of that, we have a patch product. So you can envision that the discussions are not just SE, but sort of SE plus other alternative delivery opportunities. As we've looked at Europe, and it's a bit premature to kind of get involved, we've had some preliminary discussions, but as would be totally logical, any potential European partner would like to see, you know, where we get to from a regulatory point of view, which is quite a ways out. As you go through the timeline of what Shia talked about, in the second half of 22, assuming we file in the fourth quarter of this year, the second half of 22 is when we would have regulatory clarity So sometime over the course of fourth quarter this year, first quarter next year, we would then be able to have a deeper dive with potential commercial partners. It would look like any standard, bog standard, presumably something up front, milestones and royalties that are reasonable to us and reasonable to a partner. We view it as all incremental upside for us. The pricing construct, as you would be well aware in Europe, is very different. We're thinking, just thinking out loud, which I can comment perhaps, we're thinking about, you know, narrowing our focus to more fracture patients or super high-risk patients as opposed to the sort of generic all-comers and osteoporosis. We think that could be something that's interesting. So it would be an upfront and some milestones approach. and to be determined, I would say, over the next six to nine months. But we have had some discussions, but not business, not term discussions yet. With regard to Taysian, Jim, you want to, Jim, go through the specifics in addition to the upfront that we got in the first quarter?

Sure, sure, Kelly. With regards to our Taysian agreement, we have regulatory and sales milestones of up to $40 million. $10 million of which we received in April, which we recognized in Q1. In addition to that, we have a fixed low double-digit royalty on net sales of the paliperitide in Japan.

And the Japan market, Jeff, as you would be well aware, is the largest currently, the largest anabolic market. Estimates of top-line revenue in anabolics in Japan is... somewhere in the high $2 billion to low $3 billion. Tajen is an excellent partner, and I would say resolutely focused on launching Bala Paratide. So from a cash flow point of view, once launch occurs, presumably, it could be a pretty interesting high margin cash flow for us.

Right.

And last but not least, Sal, as you said very well, Jeff, puts in calls. You know, I would just say first and foremost, as I'm sure all your other companies are, that 2020 with COVID had so many things going on with regard to patients' activity, ATP activity. So there's a lot of noise and all that stuff. But, Sal, why don't you go through with Jim some of the details that would be helpful to Jeff for – for Tim Loschus as far as the variability.

Absolutely. Jim, why don't you go first and kind of just talk through the numbers, and maybe I'll provide some commentary on each of those parts from a commercial perspective.

Certainly. Certainly. Thanks, Sal. In terms of Q1, we have our natural seasonality, as we had mentioned in our last call, where typically Q1 is is faced with some challenges with resetting of deductibles, resetting of the coverage gap to some degree earlier in the year. We have increased co-pay assistance as people are working through their deductibles on high deductible plans. We, you know, traditionally have seen it in terms of our history that there's usually a Q4 to Q1 challenge inherently. On top of that, we had some challenges where Given their duration of therapy, we do get some impact from 2020 that rolls forward and impacts us during the first quarter. We felt some impact from some variability in 2020, as we had earlier mentioned. At a high level, it was something that we see as transitory. We believe it's transitory, but partially due to seasonality and partly due to some of these transitory factors. Great, thanks.

Go ahead, Sal. I think a couple of comments from you would be helpful.

Yeah, I'd just add, the first quarter was an interesting quarter, I think, as Kelly mentioned, for the whole industry. I think some of that seasonality that we talk about, that seasonality that's related to change in coverage year for patients and kind of payer pressures and out-of-pocket costs is becoming more you know, more significant for across the industry for the first quarter. I would say that, as we said earlier, you know, our equation is simple. It's our, our demand is, you know, new patient demand, which we said is 14% higher, you know, plus continuing patients gives us our, our overall demand. So I think a little more color on, on the continuing patient is that COVID post COVID was some of our lowest new patients, dark cohorts, you know, that we've experienced. And, and, you know, that kind of catches up and creates a lull in the continuing patient pipeline. So that's why we're so laser focused on new patients. We're very confident that we get those new patient shipments or new patient demand up, that that's going to repopulate that pipeline, and we should see the demand coming from the continuing patients start to rebound starting, you know, here going forward. I'd further emphasize you know, add that, uh, as most companies, uh, there is, we all experienced a loss of patients, uh, in the transition from December to January because of, uh, payer, uh, resets and, you know, out of pocket cost issues with patients and patients dropping off therapy. Uh, and then lastly, uh, you know, it's a, it was a big deal. The February kind of winter storm, I even think it had a name. Yuri really did have an impact on us, uh, in February in terms of, uh, you know, business continuity. So I think all those factors blended together. you know, really kind of, you know, explain, you know, the quarter in Q1.

Great. Thank you very much.

Thank you. Thank you, Jeff.

Your next question comes from Mohith Bansal from Citigroup.

My question, and congrats on the progress here. Maybe, so just a little bit dwelling into Jeff's question, you also mentioned destocking in your PEDS release Could you characterize how much destocking was there, or was it a big impact on first quarter? And the related question is, where do you stand in terms of the wholesaler inventory levels right now, and could it be a tailwind for the next quarter?

Yeah, it's a – Moki, thanks for the question. It's a good question. Sal, why don't you tackle that, you know, frame it out. You and Jim, again, I think would be good.

Yeah, I think, you know, this is, you know, we talked about before, we have, you know, with this transition to our limited distribution network, we have more visibility into all the dynamics of our business, you know, than we've ever had before. And I think the one area that we have complete visibility into is because we have inventory, beginning month end inventory, beginning month inventory and month end inventory for all of our channel partners. So we have a precise now you know, be on inventory throughout the entire channel. And what, you know, simply, you know, happened is that in Q4, and that goes to part of that seasonality, you know, price changes have become predictable in the U.S. market in January across the industry. And so, you know, we saw a build in inventory in the channel in Q4 and then a destock in Q1. And I think you're right. The inventory, the channel is lean in terms of a inventory perspective. So, you know, that's something that we view as a positive for us going from second quarter forward.

So basically the demand was, the real demand was probably lower than the $60 million number you posted in fourth quarter, or it's higher than the $45 million you're posting now. So we should think of something like in the middle there as we think about second quarter roughly. Is that a fair way to think about it?

I think from a distribution point of view, the answer is yes. I think that the fourth quarter was slightly higher than in retrospect, and the first quarter is lower. And so we would normalize things out for the balance of the year. So I think that as you kind of rebound in quotes from Q1 to Q2 on the distribution channel, that would be an uptick.

Awesome, thank you. And maybe if I can squeeze in one more for Rad 11. Could you talk a little bit more about the range of possibilities or range of outcomes from your meeting with the FDA? What you are trying to discuss with the FDA, I assume the endpoints and the trial design and everything, so you should walk us through that. And then would you be disclosing it when you meet with the FDA?

Yeah, I'll turn it to Liz in a second, but thank you, Mohit. You know, we will update the market on RAD011 post clarity from the FDA. Now, that clarity is, you know, both the meeting and then, as you would be well aware, sort of, you know, written confirmation. But we have spoken internally, and we think it would be appropriate externally to have a RAD011-only update to all of you sometime after we have that written, not just with the results of the PWS discussions, but some other discussions on other things. So, Liz, you want to provide some further content to Mohit's question.

Sure. Thanks, Mohit. So, you know, this is the first time we will be talking with the agency about the program since we have acquired the asset. And so we need to go back and do some ground setting with them on our proposed non-clinical and clinical development plans, and how we plan to advance it, and what data is currently within the asset, what other things we might need to address, and how we plan to address those, all in support of our goal to have this Phase III Prader-Willi study be looked at as a pivotal study for the agency. So, you know, that's key and upfront. It covers a lot of topics. you know, quite frankly, when you talk about adequacy of your overall, you know, development plan and organization. So we'll be trying to align with them on and as well as setting expectations of what we will execute in the future. And as Kelly mentioned, after we have their feedback, we'll come back and give more detailed update on the outcomes.

Awesome. Thank you very much for this. Really appreciate it.

Yep. Your next question comes from Jessica Fai from J.P. Morgan.

Hey, guys. Good morning. Thanks for taking my questions. First one is about TMLOS, I guess, kind of volumes and commercial strategy with respect to those comments you made about 42 of the top 50 writers being orthopedic or specialist bone practices. I guess first, what proportion of Tim Lowe's scripts are being written by those 42 writers? What proportion are they responsible for?

Thanks, Jessica. It's Kelly. I guess, Sal, you'd be in the best position to kind of give, again, frame out the specific data on that. So why don't you do the, you know, handle that.

Yeah, hi, Jess. You know, in my estimation, those prescribers represent probably around 20% of the total new patients for the quarter.

Okay, got it. And can you help us think about the new patient growth for writers outside of those 42? I know you said that those 42 were kind of above average. What about the remainder, the other 80%?

Yeah, I'll just continue on. And I think that's the key for us. So I think that that market is very broad. So we have a lot of general medicine prescribers. And general med is what we would say rheumatologists, endocrinologists that treat other diseases and don't necessarily focus on bone as a primary. And so there's a lot of those prescribers. We get Brett. and not lots of depth in terms of prescribing. So I would say that, you know, for the most part, you know, the tail has been pretty consistent from quarter over quarter. And, you know, where the growth is happening is as you kind of move up, you know, in the list to the more productive accounts and, you know, the, you know, the more productive accounts tend to be these ones that are phone focused. And, you know, we've talked about the top 50, but that same situation does go, let's say, from 50 to 150, et cetera, et cetera. So, you know, that's the key is, you know, putting more focus where we have the greatest opportunity to get the most productivity, you know, from those prescribers.

I think it might be helpful, Sal, just to interject for Jessica, based on Jessica's question, for you to give high-level overview. You've done a lot of work on existing, to your point, sort of the the broad distributed activity that we have, which is in and of itself, not negative or positive, but it's not efficient and it's not where the biggest flow of patients are. So maybe one or two factoids on, for example, how many territories have, you know, five or less patients or whatever the right number you want, just to give sort of the size of scale of what we're trying to correct versus what we're trying to get to. I think that might be helpful.

Yeah, that'd be great. So Jess, I think, you know, we've talked previously about this, you know, fracture focus and we talked about the different types of fractures and we went back and we did a lot of work on our customer segmentation and we basically bucketed our customers into four groups. Three of them are bone focused. So that's your traditional metabolic bone specialist. You know, that is a physician or a physician assistant or nurse practitioner that is solely focused on metabolic bone. Then we have the orthopedic practices. So this is orthopedic surgeons or people within the orthopedic practice that are, you know, basically treating patients for the underlying osteoporosis. Then we have the, you know, cohort of bone-focused people that do spine. And then in the fourth bucket is our general medicine. I would say that what we find is in the general medicine, we do have a lot of prescribers that may prescribe one or two new patients in the quarter and may not prescribe the next quarter. And so there's a lot of transition and turnover of our tail. And so with that, that's why we're kind of even further refining our focus and trying to move our effort more to those bone focus categories without, you know, alienating or, you know, leaving, you know, the general medicine prescribers that are productive. So that's the key to optimize what we're doing in gen med. And, you know, really, you know, for those physicians that are just doing zero or one or two, you know, perhaps that's not where we put our focus because they'll never grow to what we need to, you know, where we need them to be. And then keep that focus on those gen med physicians that do have the patient flows where they are, you know, seeing and treating more patients. And then really, you know, turn and continue to shift the focus on those bone focused segments that we just laid out. I think that's great. Thanks.

Great. And maybe just following up on, I think, Jeff and then Mohit's question on the inventory swings, it sounds like you have pretty good visibility into the level of inventory in the channel. Can you just quantify the amount of the build in 4Q or as of quarter end and then the amount of the destock as of the end of 1Q? Like, is it 1 million, 2 million, 3 million, something in there?

Yeah. I would say... Jim, why don't you take that, and then, Sal, you comment would be my suggestion.

Sure, Kelly. In terms of, we have a lot of visibility to it in terms of the build and release of that inventory. I think that we're not disclosing the exact numbers, but It was roughly, in terms of order of magnitude, it represented a good portion of the decrease in revenue going from Q4 to Q1. We're not quantifying it at this point, but there was a similar instance of destocking in Q4 to Q1 of the prior year, but it was greater this year.

Sal, you want to add anything to that?

Yeah. Yeah. I think, uh, you know, the way that, you know, Mohit kind of talked about it is the way I think about it. I do think that there was a slight pull forward, uh, that, uh, we were unawares, uh, you know, given the visibility and, uh, when looking back after we have a more robust reporting, I think, you know, that's right. So, um, you know, a, the put it this way, the, the, uh, buy-in in, in the four quarter, was equally offset as the D-Stock in the first quarter. So I do think it was a phasing issue between the quarters.

Okay, got it. And then just a couple on Timla's patch. Where do you stand with respect to generating stability data for the commercial scale Timla's patch? And you also talked about having completed the study comparing PK of the commercial sterile patch to the initial Phase III product. and kind of moving the remaining patients in the wearable study onto the commercial sterile product. How many patients do you expect will get the commercial product, and for how long on average? Can you just elaborate a little more on that shift?

Yeah. Thanks for those questions, Shai. You should take it. Yeah, I just would comment that there's tons and tons of work. You know, this is sort of behind that. behind the curtain work, which is so critical and technically challenging. And Shia and our partners and her team have done a great job on this. So Shia, you want to frame out those answers to Jessica's questions?

Absolutely. Thank you, Kelly. And thanks for the question, Jessica. Really great questions. So I think your first question, if I got it right, is when do we put the product on stability? We put the product on stability as soon as we made registration batches for in our small scale of the equivalent sterile product. So that was months ago. And so we'll quickly get that data and we'll put it into the NDA submission. Since now that we've had the bioequivalence, which is comparing our low bioburden product that we've put in phase three to our sterile product, which was a huge win for us, it de-risks the program, right? And it gets us into that area where we say, okay, we're confident that we can build, you know, make commercial equivalent sterile product at Thermo Fisher and our partners. So I think that was part one of your question, right? Part two was with regards to, and maybe Kelly and Sal, you can comment on this as well, is what is the segmentation of, you know, patients that will be on the patch versus, you know, how we're positioning it?

I think, sorry, it was for the completion of the trial, right? So the crossover from, exactly. It was within the trial completing from into commercial product, approximate estimations.

Yeah. So, yeah, so we are, you know, as we've enrolled, it's a one-to-one randomized study. And we're about, I would say about halfway through completing our patient's enrollment as far as they're completing the study. And we're on track for our top-line results at the end of this year.

And I believe, Shia, the FDA had some guidelines for their wish for how many patients would be switched to commercial product. They had a certain percentage.

Yes. So the FDA said as many patients as you can get into sterile product. And so we are, half of the patients are off, so we're about between 20% to 30% of our patients should be on the sterile patch.

Correct. So that, Jessica, so the target with the agreement with the FDA was at least 20%. We would feel, you know, with all the success that the technical team has made, that we'll be able to check that box and then discuss the full filing with the FDA with that information, you know, incorporated into the filing.

And was it at least 20% for a certain period of time or just at least 20%? get some exposure to that commercial product.

I think it was the latter.

Exactly. Okay.

Thank you.

Yeah, no problem.

Thank you. Your next question comes from Anamil Simimi from Stiefel.

Hi. Thanks for taking my question. I had a couple. So I guess congratulations on the Medicare win. I'm a little bit Curious, putting aside seasonality and some of the destocking shifts, if the Medicare program is going to maintain a level of gross net at much higher than before the gross net adjustments. So that's one question. And the second is, you know, with your shift to more metabolic bone specialists and orthos, What do you see in the landscape that competitors are doing? It makes logical sense that you want to focus on that. So where are your competitors in that landscape? And then finally, I also noted the discussion on the black box with regard to most of the – so can you discuss that with us and what specifically you're looking for? Is there any upside that we can potentially see from any kind of discussions there? Thanks.

Thanks, Annabelle. Maybe we start with your last question first, Shaya. Maybe you could take the work that you and the team, Bruce, et cetera, are doing on that. And then, Sal, I think you probably would take the other two questions. So, Shaya, why don't you start?

Yep, sure. Thanks. So with regards to black box warning, we have submitted a supplement to the agency with a 10-month review. We submitted that in December of last year, and we justified it based on the fact that the removal of the black box is regards to the class of drug. We are in the same class as Certeo, and we've included in there additionally that in our post-marketing data that there's a really justification to say that we can remove this and that the product is safe. so to remove the black box. We're also requesting in that same submission the additional dosage and administration duration of the treatment. Our PDUFA date for response back from the agency should occur in October of this year. So we're feeling good about that. We've had some communication with the agency and responded back to them on their questions.

And the other two questions I just would preface it, uh, before Sal talks, um, you know, uh, Annabelle, as far as competitors and what they're doing, um, there's not that many competitors. Um, what we can tell you is we know, I mean, we know which patients actually would have the highest utilization and clinical need for a bone strengthening, um, uh, asset. And, uh, that's continues to get reconfirmed and overly reconfirmed by, uh, people that are helping us sort of sort through that. So, Sal, you want to just take sort of that, you know, the bone and the fracture folks and that sort of activity relative to, I think, maybe historically sort of the anabolic wars and what everyone's doing and how you analyze all those things. But we're trying to be very focused on where the most patient flow is and Again, the other thing, which is not news to anybody on this call, but one of the challenges of osteoporosis is 80% of the people are asymptomatic. So we're trying to narrow down where we focus and where the most patient flow is and where we can be most efficient. But, Sal, you want to take that from there?

Yeah, absolutely. I would love to. I think there's good momentum, and the momentum is based on that there continues to be a tremendous unmet need for postmenopausal osteoporosis patients that suffer fragility fracture. And the unmet need is secondary fracture prevention. And there's a lot, you know, of different organizations now making even more noise than before on this topic. And I think the one most interesting, you know, group, and there's been a paper published, you know, put out by the American Orthopedic Association where it was actually two world-renowned orthopedic surgeons who talked about the importance of bone optimization and the importance of treating the underlying condition of osteoporosis in overall bone health. So I think that there's a great momentum in the medical community around the importance of secondary fracture prevention and the importance of treating the underlying condition and everyone doing more. And I think it's very encouraging that the people who see the patient at the time of their fracture, you know, are starting to, you know, look and, you know, realize that, you know, they have a bigger role, you know, in that. So that's one. As far as the, you know, competitors, you know, we have one. And, you know, I would say that they are very much focused in the same way we are, you know, on the, you know, fracture patients and important there. So I think there we're unified, you know, as an industry and the two people are involved. and the medical community of the importance of secondary fracture prevention. So I think that we are doing and going in the same direction on that topic. And, uh, Annabella, as far as the second one, I think that was a very good question you asked me about Humana and you're absolutely right. I've been doing these things for a long time, but the, you know, what's very encouraging is that with Humana and with Medicare, we tend to get, you know, rapid uptake of new patients starts given how controlling, Medicare plans are in terms of the before and after. So you're right to say that, of course, in order to get access, we had to basically concede price in the form of an agreement with Humana, but we're very confident At the end of the day, it's about, you know, net revenue. And, you know, that deal and that access will lead to increasing net revenue, you know, very rapidly in the next couple of months.

Got it. Can I just ask a follow-up on the orthos? So you just mentioned there was great momentum for the desire to treat secondary fractures. Are orthos typically the ones that use these anabolic agents? I guess in the past you go to an ortho, you have a fracture, and they refer you back to your general physician or possibly an endocrinologist. So is this a new treatment area for them? Are they comfortable with it? Are they used to it? Just any color that you can give around that.

Sal, why don't you, and I would, some introductory comments is the orthopedic surgeon isn't going to, they're not going to spend any time really on this, but they recognize, I think, more broadly now that, you know, ongoing bone health and follow-up, particularly for a certain age category and obviously postmenopausal women, you know, you automatically have osteoporosis. So what we have found, the best traction we have with accounts that are either completely new or relatively new are in, I think in general, I think Sal can correct me, sort of rheumatologists who have set up relationships with orthopedic offices and or practices, and they get referrals post-surgery or post-treatment to all the patients. So, Sal, you want to broaden that commentary or even correct it?

Yeah, absolutely. I would love to broaden that. I think that's right, Annabelle. That's why it's hard work to do. But I think what's happened is that everyone's acknowledging that it's pretty tragic, but less than 10% of patients who are treated for a fragility fracture actually are given a consultation for the underlying condition. And what's happening is, and a lot of literature says that those people that suffered that fragility fracture are six to 12 times more likely to suffer a subsequent fracture in the next 12 months. And that's what the tragic situation is. And I think what the, you know, the bone, you know, treating community and orthopedic community is realizing is that, you know, as part of the care pathway, when they do follow-ups with patients, even if they don't feel comfortable in treating in their practice, that it's important, you know, that they ensure as part of the care pathway, you know, that somebody is giving that consultation on the underlying condition. And I think that's what's different is that people are starting to have more of a mind of the coordination of care with these patients, not just fix the fracture and then kind of they go off and have a risk of having a second fracture. And I think that that's really and particularly important for people that treat vertebral compression fractures because of the nature of that condition. you know, of that treatment and, you know, wanting to prevent, you know, the secondary fracture or prevent the second fracture from happening. So I think that's kind of, you know, what, you know, where so if it's not treat yourself, which some do, and some do, you know, have staff that do that, you know, or they, you know, refer to a metabolic bone expert, but in the very least, you know, ensure that that patient is getting a consultation for the underlying disease and having an opportunity to get treated. Okay, great.

Thank you so much. Your next question comes from Vikram Perhort from Morgan Stanley.

Great. Good morning. Thanks for taking my question. So just two quick ones for me. First, on TMLOS in Europe, could you just give us a sense of what the gating items are and what the pending to-dos are for you internally between now and a resubmission in the fourth quarter? And then my second one was on Rad 011. So understanding it's still relatively early days, but looking forward, how large of a commercial and Salesforce build-out do you think you would need for this asset in Prater-Willi if and when the time comes for commercialization? I just would like to get a sense based on your diligence of how this patient population is positioned across the U.S. and how you're thinking of best reaching them when the time comes.

Thanks, Sir. Kelly, I'll do the second one first. Yeah, there's around 22,000 to 25,000 predatory patients in the U.S. They're highly concentrated on where they receive care. The care is also, as Liz could attest, and Rupert, it's integrated care. It's typically not a single doctor. It's a group approach. Sort of Early days would refine it, Vikram, but I would say sort of the commercial team, commercial defined as the face-offs to those doctors. We are blessed within Radius of having an outstanding medical market access group, so we could certainly leverage that. I would say on the sales marketing side, you're looking at, you know, $20,000, 20 to maximum 30 people would be adequate, if not more than enough to cover the main centers. Um, so it's, it's a, it's not a big group. Um, they'd be very focused. Um, and, uh, you know, I'd be comfortable saying that now and kind of just with the asterisk that we'll, we'll, we'll refine it. We'll refine it further, you know, probably over the course of the next nine to 12 months. Um, And with regard to Europe and the Bala Paratide, we're in great shape. Maybe, Shaya, you want to add anything to it. But, you know, we're sort of in mid-flight. I think most of the things that we have needed to do, we've done, and it's now finalizing things. But, Shaya, why don't you give Vikram your thoughts?

Sure. Thanks. Thanks for the question, Vikram. Yeah, so as I mentioned earlier, we submitted the letter of intent in March. And what we're waiting for is meeting with the rapporteur, co-rapporteur, which should happen sometime in the May timeframe. And then, you know, we're in mid-flight, as Kelly says, is pulling together the dossier to be submitted in our fourth quarter. And I think we're on track for that.

Yeah, we've spent a lot of time, Vikram, on, you know, post, you know, as Shari said, real-world data, and it's been, you know, we have a lot of it, and it's all... It's all rather compelling directionally. So that's, you know, we're in good shape with all of that. And we've had a fair number of discussions in Europe with various countries. So we have a real good sense of what we have, what we need to deliver, and how to deliver it. We appreciate the question. Great.

Thank you. Your next question comes from Douglas So from HC Wainwright.

Just following up on the sort of new focus on bone specialists, I'm just curious, given the shift that you've seen and sort of nice growth, what were they largely prescribing? Meaning, are they switching from Forte or are they using, you know, Genusamab? I'm just curious, what were they using prior to sort of using starting to switch to Temblos? And generally, not just the ones you've switched, but, you know, broadly, what's the sort of standard of care at those centers right now?

Yeah, I'll let Sal answer it. But, you know, and Doug, thanks for the question. You know, Sal has all the numbers, but, you know, you'll be shocked, or I was certainly shocked as a relative newcomer here, but the vast majority of patients have no therapy. And so it's not a switch market, really. So, Sal, why don't you elaborate?

Yeah, that's exactly right. There's not much more to say, Doug. I think Kelly said it, you know, most of the time these patients tragically are not being, you know, consulted or diagnosed or even treated for the osteoporosis. So I think it's usually a situation from very little, you know, so there's, you know, that's why we're very, you know, excited about the opportunity and why we're, you know, so focused there.

And I would say that we've listened to, you know, we have obviously a lot of reach out to different people, but any number of orthopedic surgeons or interventional radiologists, you know, they kind of understand now. And this, you know, with sort of population aging and bone fragility, I think it's becoming more and more recognized that, you know, prospective bone health, once you fix an event, in quotes, it's got to be incorporated into patient care. And, you know, again, we're a small company. We don't need to turn on thousands and thousands of places. You know, a few hundred will make a gigantic difference in our business. So, I don't know, Sal, were you going to add more things?

No, no, that's it. I think that generally people are surprised, you know, with this kind of, you know, you know, what they call the bone health crisis in the nation, I think a lot of people are surprised that these patients that they treat don't make it back to the primary care and don't get the consultation, don't get treated for underlying conditions. So that's what it is. I think it's just a gap in apathy in the treatment paradigm and the pathway. And it seems like there's a group of people are now saying is that, hey, look, either we have to do something or we have to figure out how something's done for these patients.

Yeah. And if I could just have a follow-up, I mean, is it a sense that those providers, you know, is it just a misconception around the safety, the efficacy, or is it just sort of a sense of, you know, sort of an inclination not to treat because of, like, you know, bad experiences with the bisphosphonates? I'm just curious just sort of what's leading it because clearly this is such a, you know, such an important health issue, and yet there seems to be such an obvious, you know, sort of answer. Yeah. Yeah.

I think, uh, you know, it's, and that's what the challenge is. I mean, you know, orthopedic surgeons don't typically treat, uh, you know, chronic disease or underlying diseases. So I think it's, uh, you know, not something that's in their traditional flow. So, you know, that, that's what the issue is. It's really, uh, you know, hasn't been the responsibility, you know, historically, at least the perceived responsibility. So I think it's just, again, it's a gap in care. It's the handoff of a fragility fracture patient from an acute situation when they have the fracture to when someone fixes the fracture, you know, and there's just not an appropriate timely handoff, you know, to somebody that might, you know, be in a position to give the consultation and, you know, treat for the underlying osteoporosis. And that's what's tragic because, again, like I said before, that these patients are more susceptible to a second fracture than the first year, you know, after their first fracture. So, You know, that's just what it is. It's just a kind of inefficiency gap in the care pathway. And so, you know, that's really what needs to be addressed holistically.

Great. Thank you so much. Thanks, Doug.

Your next question comes from Raj Patel from Farallon.

Hey, guys. Thanks for staying on extra line today. No problem. Long queue of questions. But just big picture, outside of the inventory destocking, is there anything else that you didn't really expect? You know, I think everybody keeps asking about that, I think. And my second question is the reaffirmation of the $250 million. If Q4 was a little bit... exiting 2020 was a little bit of a lower run rate because of more inventory stocking than you anticipated. Can you just provide some color around your confidence in that number? You know, for the rest of the year, you need some steep sequential increases.

Yeah, Raj, thanks for staying on yourself. Yeah, it's good. I know, I know, I know. So we appreciate that. I would say, give you my view, the big picture, just to quote you on the first quarter, the piece of the equation that was something out of the norm of what we were expecting was the channel. So we will normalize that. Q2, 3, and 4, that will just be all normalized. And so that's the only thing that we, you know, if you take the equation of how do you get to net revenue, that's the only thing that was a bit of an anomaly for a variety of different reasons. Patient kept growing. You know, overall, patients grew. We had some gyrations in the growth. January was strong. February was not strong. two reasons, you know, much shorter month. And, uh, as Sal said, sort of the whole Midwest of the country was shut down with snow and ice. And that's, that's a double digit part of our business actually. So, you know, a week of that kind of has some impact. February was low. March was back up, uh, April early numbers, uh, as far as new patients and activity is good. Um, uh, inventory management and balance, uh, Q two, three, and four all look fine. Um, and we're very confident in that. Um, we're, we're also just re, you know, reaffirming two 50. Um, you know, we're, we're highly confident on that number. Um, from everything we can see again, you know, it's, it's, it's complicated. Uh, the, the, the new patient numbers we give, cause that's our most important internal metric. That's a, that's a prospective indicator of future revenue. And then you have other components of the puzzle like, uh, uh, that price and, uh, inventory and other things, which are more coincident with, uh, you know, any given day, week or month or quarter from a PNL point of view. So as we look forward, if you look at our, our, our, uh, patient numbers that we started, uh, sharing in the fall and then now for sure. Now the continual building of patient numbers, you know, gives us high confidence that the, uh, the target for the year is, um, is very doable. And that's why we reaffirmed it. I would also say that we are we are hyper focused on you'll hear us talking about EPS more than you've had probably ever. You know, eventually, you got to be an earnings company. That's a goal that we have. The operating leverage you have is significant. And the SC business from a margin perspective is highly attractive. So It doesn't take a lot from a sensitivity point of view for us to continue on the bottom line, both EBITDA and EPS, to continue to make outsized improvements, and that's certainly a big goal for us as well. So I broadened the answer based on your early morning awakeness on the West Coast, but I hope all of that frames it out for you logically.

Yeah, no, that's helpful, and those final comments at least match my model, so That makes me feel better about it. But one question on the new patient expectations. What should we be looking for? You know, that 1700 plus number in March, it obviously will be, it'll bounce around. And I know the market's going to, you know, be hyper-focused on a monthly number, right? You guys are putting them out monthly. But what's the right, what are your expectations on those numbers going forward?

Well, you know, I'll comment and then Sal could add, but I mean, you know, compounding is a wonderful thing, right? So we want to continue, it's not like we have a set number, you know, for any given month, but we, and we started with three months, but we expanded slightly to four months to take out some of the noise, but You know, the way we look at the business, trying to be transparent to shareholders and the marketplaces, you know, as long as we're above the four-month moving average, the trend is your friend, and the compounding, you know, works with you if you look at average duration of treatment. So it's not like we have a set number for each month. Our number is to grow from the previous four months of activity. So every month that is what we, you know, that is our goal. it doesn't mean we're going to achieve that every month. And then, you know, sort of the moving average kind of resets a little bit anyway because you're not going to have massive volatility. But what we expect internally is to grow that number relative to the previous activity every month. You want to add anything or refine that answer, Sal? You know, please go ahead.

Not refine, just add. I appreciate the thought about the monthly, you know, perhaps some volatility. And I think of it that way, too. And I think, you know, we're looking for just sustained, persisting growth. So as Kelly said, as long as that, you know, we are, you know, above that four-month average, and quite frankly, for the long view, as long as that four-month average continues to improve as well versus the prior four-month average, these are the types of things, just getting that sustained growth so we can, you know, get that patient pipeline, you know, built up significantly, you know, so that's all I would add there.

And just to add more, Raj, you know, as I tried to frame that early on, you know, the SEB is a great business. We want to grow that. And then the incremental upside, which the company has, you know, spent time, energy, and money on, You know, the mail readout is important. The patch readout is important. And we've added some, you know, incremental international locations, while none of them other than Japan will be a significant, you know, change in trajectory. But if you sum up the, you know, sort of somewhat globalizing the asset, you know, we tried to position things where we're almost to a point where, you know, it's all upside at various levels of, you know, of opportunity. And, you know, that's where we're close. We're very, very close, obviously, from a P&L sustainability point of view.

Got it. And one last thing. Yeah, go ahead. Yeah, I know it is. One last thing since you mentioned Japan. Do you have any expectations you can share on Cajun's market share over time? How competitive is that market Do they have competing products? Any of that?

We have done our own internal modeling. There was an internal model, which we're actually redoing as we speak. Taygen is positioned in the bone metabolic space very powerfully in Japan. I would expect them to be... you know, a top two or three participant in the space. Do they expect to be a top two or three participant in the space? I don't have market share necessarily. We have some internal numbers, which we won't share at this current time, but I would just say when we start thinking about translating all this into EPS opportunity, it's, you know, it's not insignificant for us at the apex, Now, the slope of the curve is something we're drilling in a little bit more on. So I guess we will come back to the market when we have a framed out part of that piece. I think that's a legitimate thing for us to sort of frame out for the marketplace. Here's the range in Japan that we think is possible.

Okay.

Thanks.

I lied. I've done more. You focus on different types of prescribers. Are you seeing anything different on the duration of therapy of their patients?

That's a great question, Sal. You want to handle that? Yeah, that is a great question. We have not yet. It's too early. I haven't seen the data. I just know that right now our persistence hasn't changed. It's you know, too early to see the impact. I think that there's two factors together, you know, that in my estimation will improve duration of therapy, and that is the focus on patients that are, you know, very severe and have the history of fracture, so more motivation to continue treatment. And I do believe that all the work we did on the limited specialty pharmacy network inevitably is going to ensure you know, better experience through specialty pharmacy with a better chance for patients to stay on therapy throughout. So, you know, perhaps we'll, you know, comment more on that next time we have a call.

Great. Thanks, guys. Okay. All right, Raj. Thanks for getting up early. Appreciate it.

No problem.

I'm sure no further questions at this time. I would now like to turn the conference back to Ethan Holdenway. Thank you.

Thank you, and thanks, everyone, for listening in to the call. As a quick reminder, a replay and the presentation will be available on our website following the call. Thank you again. That concludes our Q1 2021 conference call.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all disconnect.