Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals Fourth Quarter and Full Year 2022 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers presentation there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dave Connolly, Executive Director of Investor Relations and Corporate Communications. Please go ahead.

Thank you, Michelle. I'm Dave Connolly, IR here at Rhythm Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the Investors section on the Investors page of our website at ir.rhythmtx.com. And this morning, we issued a press release that provides our fourth quarter and year end 2022 financial results and business update, which is available on our website and as listed on Slide 2. And as listed on Slide 2 is our agenda. Here with me today in Boston are David Meeker, Chair, Chief Executive Officer and President of Rhythm Pharmaceuticals; Jennifer Chien, Executive Vice President -- Executive Vice President, Head of North America; Hunter Smith, our Chief Financial Officer; and Yann Mazabraud, Executive Vice President, Head of International is on the line joining us from Europe. And I'll remind you that this call contains remarks concerning future expectations, plans and prospects, which constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual or quarterly report on file with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to David, who will begin on Slide 5.

Thank you, David, and good morning, everyone. Thank you for joining the fourth quarter earnings call. And we are going to talk about earnings, which look good. And this week's announced acquisition of Xinvento. However, before we do that, I want to reflect for a moment on this company's journey. It was almost a decade ago when we published the first case reports in the [indiscernible], describing the remarkable effect of setmelanotide in two patients with POMC deficiency. Since then, we have learned so much about the MC4 receptor pathway, the associated genetic deficiencies, the importance of hyperphagia and energy expenditure in the development of obesity. At the same time, we started to learn about what it means to live with one of these rare diseases. Complete lack of awareness in the part of the healthcare system, the relative shortage of experts, the almost complete lack of genetic testing, all compounded by the societal and medical bias, which confronts the individual and family living with obesity. As a mother one child with BBS said, when asked how bad can hyperphagia and obesity be when your child may be losing their site. A response, people are kind to blind people. So in Slide 5, the challenges of living with the rare disease were further highlighted this week as we mark Rare Disease Day at Rhythm as a guest speaker, a mother of two children with BBS who describe the incredible challenges of living with the hyperphagia. This severe preoccupation with food and the associated abnormal food seeking behaviors and how her child and her family's life has been changed since starting in [indiscernible]. And Rare Disease Day leads into Obesity Care Week and World Obesity Day on March 4, which brings obesity to the forefront as a disease that requires a…

Thank you, David. I'm going to be starting on Slide 13 today. We are excited about the current status of our U.S. IMCIVREE BBS launch. We remain focused on our efforts to see the diagnosis of patients with BBS and educate them on the availability of IMCIVREE. The only FDA approved therapy [Technical Difficulty] MC4R pathway, a root cause of hunger and obesity in people living with BBS. Through all the efforts of our cross functional team, we have seen continued progress and success across the journey from diagnosis of BBS patients, through to securing access and maintaining patients on therapy due to the benefits they receive. Next slide. We are pleased with the progress in achievements made in the second full quarter of launch. As we did last quarter, we will share with you today key metrics we believe reflects the progress of our launch, focusing on prescriptions, prescribers and care approvals for reimbursement. Since IMCIVREE was approved of BBS by the FDA on June 16, 2022, and through the end of the fourth quarter of 2022, we have received more than 200 new prescriptions for BBS patients coming from more than 125 physicians. This breaks down to more than 100 new -- 120 new prescriptions between June and the end of September and more than 80 in the fourth quarter. Given that 20 clinical trial patients had converted to commercial prescriptions during the third quarter, we are pleased to see the continued growth in quarter-over-quarter prescriptions. Importantly, we have received payer approval for more than 100 of these prescriptions since launch. The demand for IMCIVREE is strong. Physicians are writing the prescriptions and patients are experiencing benefit on drug. On the next slide, we'll take a closer look at IMCIVREE prescribers response. Not surprisingly endocrinology, both pediatrics and…

Thank you, Jennifer, and good morning. I will start with the Slide 20. So in the international regions, we had a very strong year and a very strong fourth quarter as well, making significant progress in securing access for IMCIVREE [indiscernible] indications. And in parallel working intensely at market access execution for Bardet-Biedl syndrome. IMCIVREE is now available in eight countries outside the United States, and we are looking forward to continue the execution this year. As you can see on the picture, the international team came together mid-January to kick off the year with a focus on market access, patient identification, launch plans and operational excellence. Next slide. For POMC, PCSK1 and LEPR patients, we have identified approximately 100 patients being cared for in medical centers in EU4 and the UK. And the estimated prevalence is approximately 600 to 2,500 patients in Europe. For POMC and LEPR, we are now fully launched in the UK, in Germany, in the Netherlands and in Italy. We achieved paid early access in France, same in Austria and Turkey, and we also have an early access program in Argentina in place. Compared to the United States, we know that the community and regional networks in Europe are better organized for these patients. While the numbers are still small, we are in positions to leverage that existing rare disease infrastructure. And we are already doing so. Next slide. For BBS, we have made significant progress since we received the marketing authorization from the EC in September last year. And like for POMC and LEPA indications, we are in positions to leverage the existing rare disease health care structure. BBS is a larger population, we believe the EU prevalence estimate of 4,000 to 5,000 patients as David has detailed. We now have approximately 1,500 patients…

Thank you so much, Yann. Turning to Slide 24. As we begin 2023, well capitalized with $333 million in cash on hand, sufficient to fund all planned operations into 2025 as we continue to grow as a global commercial stage biopharmaceutical company. This cash guidance includes the impact of projected milestones and R&D spending associated with the Xinvento acquisition. We recorded $8.8 million in net product revenue from IMCIVREE in the fourth quarter and $16.9 million for the calendar year 2022. Quarterly revenue marked an increase of $4.5 million or 105% over the third quarter of 2022, driven primarily by IMCIVREE sales for BBS in the United States, as well as increased POMC and LEPR sales in our international region. U.S. sales represented 84% of total Q4 net product sales and 85% for the full year. Cost of goods sold for the fourth quarter was $1 million or about 11.7% of product revenue. Cost of goods sold consisted of $440,000 royalties due to Ipsen under our original licensing agreement, $400,000 product costs related to commercial sales and product distributed under patient assistance programs and about $200,000 related to the amortization of our previously capitalized sales based milestones. R&D expenses were $23.5 million and $108.6 million for the fourth quarter and calendar year 2022, respectively, on a quarter-over-quarter basis R&D expenses decreased by $8 million. On a sequential quarterly basis, this represented an increase of $2.4 million as compared to the third quarter of 2022, primarily driven by increased spending on clinical supply and materials. Clinical trial costs remain largely unchanged as decreases in older studies offset increases in costs associated with the ramp up of activity for our pivotal Phase 3 hypothalamic obesity and M&A studies. SG&A expenses were $26.3 million for the quarter and $92 million for the year…

Thank you, Hunter. So I'll quickly share these last two slides before moving to questions. So Slide 27, as noted we have several trial starts and top line data readouts this year, which we talked about, as well as several market access milestones in a number of ex-U.S. markets with Yann detailed. Slide 28, just reminding you, we have three main [indiscernible] areas for this year, maximizing the BBS commercial opportunity globally, executing on our Phase 3 trial in hypoglycemia obesity and continued expansion through clinical development for setmelanotide in these other trials and now our assets from the Xinvento acquisition, which again we look forward to moving forward as rapidly as possible. And with that, we'll open it up for questions. Back to you, operator.

[Operator Instructions] Our first question comes from Philip Nadeau with Cowen. Your line is now open.

Good morning. Thanks for taking our questions and congrats on a successful quarter. First question is on the BBS launch. The pace at which you're adding prescriptions is impressive. With 200 at year end and adding 80 a quarter, the simple math would say you'd be over 500 by the end of 2023, which is the vast majority of people who are in the BBS registry. Can you tell, one, whether you're adding new patients to the prescriptions or are you giving patients -- prescriptions who are not currently in the registry. And two, can you talk about new patient identification more broadly? Is it possible for this rate of prescriptions to continue even beyond 2023.

Thanks, Phil. Jen?

Thanks for the question. So you asked about the CRIBBS registry. We have great relationships with the folks at the Marshfield Clinic. They are incredibly dedicated to the BBS patients under care. When we think about the CRIBBS registry, however, there are privacy policies in place. So we at this point really don't have any visibility in terms of the overlap of the patients that are in the registry versus the patients at ACP that we have within our view at Rhythm. So that's one piece. To your point in terms of the first question, I would say that we've been very happy with the level of the demand for this product. It speaks to the need and the differential impact in terms of the hyperphagia and the patient population for them to be seeking treatment, not only for their obesity, but the underlying hyperphagia now. And so we are very much focused in terms of pull through of opportunities. There still remains opportunity in terms of the physicians that we already have identified with patients that they are treating with BBS and pulling through those patients onto therapy through our interactions and education efforts. And to your point, we continue to be ultra-focused in terms of identifying additional patients to add to our view. This include patients that are already diagnosed with BBS that are lost in the system and we have different mechanisms that we're going about in terms of finding those patients, as well as educating those patient -- potential patients out there as well as ACPs on the differential diagnosis for BBS [indiscernible] and that could expedite patients to get to a proper diagnosis. So there just remains a lot of opportunity out there.

And is there any sense internally whether what we saw in the second half last year was a bolus? Or do you think that rate of prescriptions could continue actually even through 2023 given its impressive rate?

Yes. I mean, I would say that there was certainly pent-up demand for any disease area where there's no therapy that's available for years and years and years and when something becomes available and it's quite interesting for patients who work really trying to find a therapeutic option. We also had about 20 clinical trial patients that were converted to commercial scripts, so that was more in Q3. So with that said, I think the growth that we saw in Q4 was quite exciting to us. And as we move forward, we just have continued conviction about the needs. And once again, our focus is just around getting those patients to a quicker diagnosis of the journey -- diagnostic journey [indiscernible], so long for these patients.

So, Phil, just to reinforce a couple of things that Jennifer said there. I want to remind that one of our common themes in rare disease world don't trend it in a linear fashion. So that certainly goes for revenues and it -- early on and also goes for the script. So whether it will be 80 per quarter and the like, in calls for sure or not, it will continue. That will also be lumpy, but as Jennifer said, we remain incredibly encouraged by the strength of the demand here. And the one other piece I referred you to, as Jennifer highlighted, was the 22% of physicians who were not engaged with what we’re writing. These are patients who were not on our radar. So back to the different ways patients are coming into the system. A, we may find them or B, they may find us. So again, a lot of thing [indiscernible].

That's very helpful. And then one last question on the pipeline. On the DAYBREAK data that we're going to end the second half of the year, do you think you'll be in a position to release results from all the gene types in the study or will it be a snapshot as to the most mature data that you have at that time?

Probably a blend of that answer in the sense that, as you know, remember we start off looking at 30 genes. And then during the course of the trial, we amended that based on some early results of genes not being so interesting and also some of the genes were just so rare that we really couldn't enroll them. So we stopped looking for them, which doesn't mean they're not out there. It's just that they'll not be part of DAYBREAK. So we'll try to give you a sense of -- we will give you a sense of sort of the larger landscape and how we narrowed it down, but the areas of interest will be those genes for which we focus down on, we're able to enroll enough patients to draw some conclusions, which will be a number much smaller than the 30 and we set the expectation that will be probably on the order of five plus or minus, maybe as much as 10, but it's -- that's going to be the kind of data and the focus is still here.

That's very helpful. Thanks again for taking our questions.

Thank you.

Please standby for our next question. Our next question comes from Derek Archila with Wells Fargo. Your line is now open.

Hey, good morning everyone and thanks for taking the questions. Congrats on all the progress here. Just a couple of questions from us. I guess maybe first, as we are now in 2023, maybe just any commentary on more recent trends for scripts and particularly around BBS patients? And is there any seasonality as you should think about kind of this first quarter relative to the rest of the year? And then second question, given that you have 100 reimbursed scripts, I guess, simple math, does that kind of imply like a $30 million kind of annual rate here in terms of, if all those patients stay on therapy. And I guess if that's true, I guess, how does that impact your thinking on where current consensus is, which is like $35 million to $66 million for 2023? Thanks.

Thanks, Derek. Thanks a lot. So what we'll do is, I’ll let Hunter the consensus question just to…

Yes, I don't think we want to get into the commenting on consensus. It's inconsistent with our not giving guidance. Having said that, the spread is quite wide and we expect as we continue to -- as we continue to execute, I do expect the range of estimates to narrow.

Jennifer, several questions there. One on just the overall trend again and seasonality quarter on quarter in rare disease world, this one specifically.

So speaking to the seasonality, particularly it’s unusual for the fourth quarter to potentially be light as far as November holidays, as well as [indiscernible] holidays in general. What is interesting is, for this particular therapy as far as those family gatherings are surrounded by food. And it's also a potential opportunity as children are out of school for [indiscernible] initiated on therapy during a period where they are on break. And so we did see some of that happening as well or heard some of those [indiscernible] who wanted to actually initiate therapy during this time that may have been a downtime in other areas. But with that said, I don't think that there's going to be much like seasonality. I think it's really more based in terms of the physician, when they see the patient and getting through the reimbursement process to then be able to initiate therapy. So it's an ongoing process there.

Yes, that's very helpful. And then just on Germany, I know you guys are prepping for launch and maybe kind of discuss what you're doing there. And then I think you said there is 1,500 BBS patients that are identified in Europe. I guess how many of those are in Germany?

Yann, can you take that?

Yes, sure. So I will not may be tell you the exact number, because, first, we don't know it exactly, but of course, it's a significant portion of it. And as often in Europe, I would say that this patients are localized in centers of excellence. So many centers with a lot of patients in each.

Thank you very much.

I think -- Yes. I mean, we're optimistic about Germany and I [indiscernible]. And I think just to reinforce some -- under some comments part of our goal in trying to give you a little more insight in terms of the breakdown between U.S. and Europe is, as we learn and we try to help you understand how Europe evolves as you do a tremendous amount of groundwork to get through the market access, get pricing established and the like. We have the advantage of better organized patient communities and centers of excellence, if you will. But there is this steady gradual start up. So it's not a world where you tend to get a large bolus and you have a very big quarter. We expect this to build very steadily over time with Germany leading us as we get approval for BBS here.

Got it. Helpful.

Thank you, Derek.

Please standby for our next question. Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is now open.

Yeah. Good morning, everyone. You mentioned this earlier, but can you just expand on the degree of white space that remains among those 125 current prescribers for IMCIVREE based on maybe the additional patients that are under their care and might be appropriate for the drug?

Yes. So Jennifer, so of the 125 physicians who've written prescriptions, how many do you think are holding other patients that they may be acting on or going to be acting?

So of the subscribers, I would say approximately a quarter of or have written -- sorry, there are around 20% or so that have written more than one scrap. So we do have already physicians who have written more than one script. Within the area of rare disease, I would say that a lot of physicians only have one patient. So it's not as normal as it would only have one patient at this point of time. But there's still, once again, remains opportunity within other physicians who have yet to prescribe for very different reasons in terms of [indiscernible], but again identifying additional physician [indiscernible] as well.

Okay. And then maybe on Xinvento acquisition. Should we expect that asset to be developed in a distinct mechanism of action or are you looking to develop more of like a best in class drug against what are some of the known targets in that disease?

Yes, I think [indiscernible] like I said, we have said in our press release that I commented, we'll provide an in-depth -- greater in-depth presentation of where that program is and what we're going after. So we're not going to reveal the target today. But I will say [indiscernible] if you will here. The biology was incredibly compelling. And why was this a good opportunity for us and as well as things you start with -- is there an unmet medical need and is the biology and approach to the problem, does it make sense and is the progress that they've made sufficient to give you confidence that you could have a reasonable probability of success here. So Xinvento checked all three of those boxes, we know it's a competitive area and I think that speaks to the unmet medical need and we've been entering into this blindly, we entered in it with a full recognition of what else is out there and how this approach might compete and we feel really good about that. So I apologize for leaving it there for the moment.

Okay. Thank you.

Please standby for our next question. Our next question comes from Dae Gon Ha with Stifel. Your line is now open.

Great. Good morning. Thanks for taking my questions and congrats on the progress. One question on the DBS launch, just going back to the sequential announcement, I believe, in the first six weeks, you have 50 prescriptions -- prescriptions followed by 120 in third quarter and then 200 in fourth quarter. So can you maybe walk us back to that initial six weeks? That 50 within six weeks seems to be fairly robust there. What happened there and is there any chance that we could see another kind of picture like that emerge in 2023 at some point or should we expect kind of going back to Phil's point, another 70 to 80 per quarter? And then a question on Xinvento. I realize a lot of details are under wraps at this point, but just looking at the board composition, it does seem fairly like it might be more ASO oriented. Am I on the right tractor or is it more small molecule or even injectable biologic? Any kind of insights that would be helpful? Thanks so much.

Yes. Got it. Jen, do you want to take –

Sure. So you were asking about the number of scripts in the first couple of weeks. So I think that’s defiantly because of some anticipated demand. So we're waiting to get off the therapy. Also a reminder just in terms of we had patients already ready that were part of our clinical study that we were converting into commercial scripts. So that's part of the explanation in terms of the number of scripts that we received quite early on. But moving forward, I think it's always a bit difficult to project, but I will outline that we still have quite an opportunity just in terms of -- as we move forward, the script that we've received that we are still working through the reimbursement process, getting those patients on to therapy is an area of focus. We're continuing to educate the physicians that do have the BBS patients, that's around the need to treat the hyperphagia and the early onset with the targeted therapy. And the third pillar definitely is to find additional patients, which I have in the past outlined, but we have very targeted mechanisms at this point in time. This is how are we going about our efforts there.

And I think all the questions and Dae Gon, your question, of course, sounds specifically, which we totally are sympathetic to and we have the same questions as we seek to understand -- better understand this opportunity. All the diseases is -- most diseases, including rare diseases, have some front loading as they go through development. There's patients who are tracking this and expecting that moment of approval and looking to go on. So there's always a bit of that front loading. I think what's been incredibly reassuring about this opportunity in BBS is that, as we've now gone deeper into the launch in the fourth quarter, I think is a good standalone quarter in that sense. The demand is clearly there. And what we hope is, one is, yes, we continue to work to find more patients, which we're doing and we're doing successfully. Second, as you build the system, meaning, you get more centers, more individual physicians who are writing prescription and taking interest, you begin to build an ecosystem which those patients who are seeking care and or think they might have BBS start to find us. And so that process will continue. And again, there's nothing about the BBS opportunity to date. That doesn't -- that changes our view that this isn't a very meaningful opportunity and ways to track some of the other well established well known examples of rare disease success stories. So we'll keep you updated and try to give you as much insight as we can, but we are learning with you.

And then, David, what about the Xinvento, if there is any –

Sorry. Yes, [indiscernible] apologies for not be more specific. So we're not going to reveal the modality that we're chasing this morning, again, I think the unmet need here, there's a tolerability issue with the current standard of care, there's some safety issues related to the current standard of care and then we think there's suboptimal efficacy. And so this solution we would hope would address all three of those. But again, stay tuned on the exact modality of the target.

Great. Thanks so much.

Please standby for our next question. Our next question comes from Whitney Ijem with Canaccord. Your line is now open.

Hey, guys. Good morning. Another kind of I guess type of runway question for you on scripts. Are any early color on compliance rate or refill rate just as we think about that new prescription number you're giving versus kind of total prescription headed into 2023?

Sure. So at first in several different rare diseases in the past and one thing that was interesting to [indiscernible] But if -- and when the patients actually feel a different, while being on the drug, that tended to lead to a higher persistence, as well as a compliance rate. So when you think about a patient population, the hyperphagia here is a key factor. It's something that just impacts them like really day to day, hour to hour. And feeling a list of that or relief of that was finally to the weight loss is something that they can feel in terms of benefit of being on drug. And so we have seen a very high compliance rate even with the daily injectable because of this. And once again, it's due to the benefits that they receive. From a discontinuation of persistence rate, it is early days, but I will say that we are quite happy just in terms of what we have seen. There was a lot of education on both the ACP as well as the patient side around expectations as well as ongoing engagement with our customers so that we could get our through the titration process and maintain them on drug. So I would say that the discontinuation rate is quite low and we're very pleased with that.

Awesome. Thanks. And then -- excuse me, one on HO. Can you remind us, are there any patients in like an ongoing long term extension study from the Phase 2? Or is there any additional longer term follow-up in HO that we should be thinking about either being collected or being presented in 2023?

Yes. So 14 patients entered the long term extension. And yes, you should be paying attention to that. Our goal will be to update that experience some of this later in the year [indiscernible] meeting and the specific abstract submission, but that would be our goal is to link it to that. But that's very important as with all of these, the original 12 to 16 weeks is a very short period of time and what everybody including regulators are looking for is durability. And so we're looking forward to being able to update further experience.

Excellent. Thanks so much.

Please standby for our next question. Our next question comes from Michael Higgins with Ladenburg. Your line is now open.

Thanks guys for taking the questions and congrats on the quarter, including the ongoing launch. A couple of questions for Jennifer, if I could. I believe in your remarks, you noted that there's some state Medicaid programs that have decided they will not cover IMCIVREE at this point. Is that something that can be revisited within this next year? Thanks.

Yes. So to your point, yes, I did outline that there are some certain states that we have patients already on path. We are very -- ongoing in terms of our efforts to continue the education process, not giving up in terms of really seeking reimbursement. And I would say that through our education efforts, we get more and more coverage decisions made for IMCIVREE as we move forward into some launch through this first year through in terms of the [indiscernible]. There are certain opportunities that we have that are perhaps more low hanging, for example, for Medicaid programs they have and [EPSDT] (ph) program that's available for more pediatric and adolescents, which is an opportunity for us to follow-up in terms of getting reimbursement. But once again, the follow-up and efforts just in terms of opening up access state by state is ongoing.

And Michael, that's really a critical point in the sense that aside from something like Medicare where there's a statute and there's certainly way to work that until the statute to changed and other companies are trying to get that change. But everything else, there's sort of never a definitive no. And we've organized it in a way where we recognize at some point, it's not maybe not be in immediate near term, but there's never a no. You just keep working this system and in a surprising way some of those no way opportunities become yes. And it opens up and that patient gets covered.

I appreciate that. Is this something that is in the single digit raise? Is this something that's really infrequent? Or is it something that's maybe kind of a 25%, 50% programs scenario, which once you release that lever, you've got another avenue of patients. So just trying to characterize the degree of this impact?

Yes. I would think as we've looked at [indiscernible] I mean, right now, and this is again a dynamic scenario. I would put on the order of 20% of the states would have that relatively harder line. And those are the ones where some of those patients will move on to PAP as we continue to fight that battle. But the vast majority, 80% are either what we call the green category and patients are moving through with an unimpeded PAP or in a mixed category where there's -- the state is still working through its response, but we've had patients through. And then there's a smaller segment that we still haven't put a patient in front of that state. And so they were [indiscernible]. But it is a relatively small percentage of the states today, which again I think is as a starting six months in, from my view, pretty amazing.

I appreciate that. One last one if I could. How many prescriptions are coming in outside of BBS. It can include on label as well as off. You've got some great data in HO obviously? I'm curious if there's any prescriptions there that you're aware of?

No. So none that we're aware of. Again, we have the Phase 3 trial up and running. The actively screening has indicated, so there's an opportunity for patients to engage there. But we don't have any insight into patients who may be “seeking off label for HO today”. For the other, again, I want to apologize. Just the POMC, LEPR world, again, we believe there's tens of patients today and that's a world, particularly in the U.S. we'll see how Europe continues to open up slightly different dynamic as Yann described. But that in the 10s is what you should expect for POMC and LEPR.

I appreciate the feedback. Thanks, guys, and congrats again.

Please standby for our next question. Our next question comes from Joseph Stringer with Needham. Your line is now open.

Hi, thanks for taking our question. Just going back to persistence rates for patients that have started on commercial drug and have discontinued, what are some of the main reasons that you're hearing for that? Is there any particular reason that stands out?

[indiscernible]

Sure. At this point in time, there is a variety of different reasons that are more like one to two at this point of time. It could be hybrid pigmentation. It could be based off of sort of loss to follow-up opportunities. What I do find interesting is, there are several discontinued for personal reasons, but our opportunities for potential reinitiution of therapy moving forward. So our teams remain in contact with the patients even after discontinuation in case there is an interest in terms of reinitiating. And we've heard this also from several physicians as well that there may be opportunity in the future for re initiation.

And just to provide a little more context, it's an important issue, which obviously we follow closely. So the current discount rate is in the mid-single digit percentage range. And as Jennifer highlighted, what's really -- I think, been highly reassuring is that the percentage of spaces that are stopping because of known side effect profiles, characterized on the order of third of that, if you will, plus-minus. And so I think that speaks to the job that, as I have highlighted, 95% of these patients content into Rhythm InTune. And so we as a company and that team has the opportunity to engage individually and there's a high level of touch there and that's incredibly valuable as people both getting expectations set in a way. Look, you're going to experience nausea and potentially vominating in the early phase but it will end and you can walk patients through and that's working. So we feel really good about the overall tolerability and persistence in general here. And then, as she said, you got a handful of patients who are discontinuing for personal reasons, which are a sense unrelated to the drug of the problem and that happens in any disease area.

Great. Thanks for taking our question.

[Operator Instructions] Our next question comes from Jeff Hung with Morgan Stanley. Your line is now open.

Hi. This is Michael Riad on for Jeff Hung. Thank you for taking our questions. First, regarding the 22% of prescribers that weren't called on by a territory manager, were they in any particular region of the country? And what is Rhythm learning from these interactions? And how could that be applied to bring in additional prescribers? Thanks.

Yes. We're actually very happy seeing this percentage just in terms of patients that are coming through not directly through the efforts of our territory manager. I think it speaks to a couple of different things in terms of our more broader based efforts and our personal promotion efforts that get to a broader set of those patients out there as well as physicians, which may be why there could be more of a skew in terms of this physician population skewing more towards like primary care physicians. But these patients are in the hands of so many different physicians as they go through their journey. So we have to be both targeted in our field efforts but also broad based in terms of outreach through other supportive mechanisms. I think that would fall into that category, of course, also relate to our presence at conferences, our ongoing dialogues and relationship with the BBS foundation and such. But I would say that, if there's a motivated physician who is going to prescribed. This is a drug that can be prescribed and managed by a very different specialty background. So we continue our education efforts with each physician who has been interested, who has put in a prescription.

Okay, thanks. And maybe a second follow-up for the Phase 3 and hypoglymic obesity. What factors would push enrollment closer to the 12 month mark. Given patients are -- diagnosed patients are well known, is it more the logistics of getting sites up and running? And finally, what would you see as the biggest hurdle for this study? Thanks so much.

Yes. It is the logistics that I think we talked about on some of the earlier calls. The trial network or infrastructure globally in the U.S. for sure as well is challenged coming out of COVID. And so a number of these sites have personnel challenges, in terms of study nurses getting things through for pure logistics as you noted. So that is the issue. The patient demand is there. Patients are -- every site that we've talked to who signed up to be part of this trial are enthusiastic and has a surprising number of patients relative to my experience in other trials in these areas. So that would be a -- your question was anything that could make it go faster [indiscernible] so that we can get all set up, we'll highlight to sites as we have already that we expect enrollment to be competitive and that could be a useful dynamic as sites have a number of patients who may want to participate and they'll be hopefully push to get them in, we are limited only by maybe their study nurse's ability to do a process, that'll be the balance.

Thank you.

I show no further questions at this time. I would now like to turn the conference back to David Meeker for closing remarks.

Great. Well, thanks everyone for tuning in. As you've heard, we remain incredibly encouraged by initial experience on BBS. The R&D programs are up and running now and executing, so we feel good about that area. And excited about a new opportunity. We'll spend an opportunity to Rhythm and Xinvento and look forward to updating on that. So that will sign up. Thanks again.

This concludes today's conference call. Thank you for participating. You may now disconnect.