Ultragenyx Pharmaceutical Inc. (RARE) Earnings Call Transcript & Summary

All right. Good afternoon, everyone, from the virtual JPMorgan Healthcare Conference. My name is Cory Kasimov. I'm senior large-cap biotech analyst. And it's my pleasure to introduce our next company, Ultragenyx Pharmaceutical and CEO, Emil Kakkis. Please note that following this presentation, we will have a Q&A session where you have the ability to submit questions via the little blue button in your conference portal. So with that, Emil, thank you for being here today, and let me turn things over to you.

Thanks, Cory. Thanks for having me today, and welcome, everyone. Ultragenyx, if you're on the first slide, I'd move on to your second slide is the legal warning. And let's move on to the next. The companies now after 10 years, been building really an exceptional rare disease company from the standpoint of building a commercial enterprise with the Crysvita, Dojolvi launch phase and growing. Clinical element catalyst now with the build-out of the pipeline, which is giving us a number of new programs with initiating pivotal studies as well as the other data streams coming forth. And finally, we've been building out the gene therapy manufacturing, the platform and its value, which I think is one of the best in the industry for large scale, high-quality AAV manufacturing. This sets us up for the next 10 years for growth of the company. If you look at the last few years on Slide 4, you can see that the 4 products were finishing their life in '17, '18 through '20, and the 4 approvals occurred. And while that's been happening, we're actively working on it through the business development side, doing efficient deals to bring pipeline in for the next stage of our growth, that there would be no dead time between these. The Dimension deal acquisition brought forth a couple of gene therapy programs, which then we've added now another one in Wilson and CDKL5. And finally, we've added the solid deal in Duchenne, bring us forward to a really strong gene therapy franchise, really one of the best in the industry. We did a deal for mRNA/LNPs with our some time ago, that first program for GC3 is now at the IND stage. We also in-licensed a program from and with creating a lot of excitement lately in our -- what's now our nucleic acid franchise. Again, like gene therapy, highly specific, sophisticated biologics that can achieve changes in rare diseases that you couldn't do with other types of molecules. In addition, we've added now Ostein Perfecta, a nautical nanomized Atrium AB, which is we'll improve the bone and othogenes and perfect. And that will fit beautifully within the franchise we have in the bone endocrine phase. If you go on to Slide 5, you can see what those franchises look like. The CNS Angelman on the left and some other non-clonal assets not shown. The bone endocrine franchise, which has setrusumab for OI, which is now on deck well entering Phase II/III, along with the prior programs escalation to, which are now in launch phase. In metabolic, we have 2 approved products, but now multiple products in entering clinic from our gene therapy franchise. So this puts us in a good position to build these 3 franchise and driving revenue forward as a company. If we put that into context on Slide 6 of the overall portfolio, you can see the diverse breadth of both modes and types of drugs and type of diseases from smaller indications to now 4 different larger indications as well in the portfolio. And I think if you look at this portfolio, it's really one of the best in the industry in the rare disease space with multiple programs entering Phase III in multiple programs there potentially larger and a diversity that you rarely see out there. If you look at Slide 7, you can get a sense for our commercial performance to date. We pre-announced our $137 million to $139 million in Ultragenyx Crysvita revenues and also projected for 2021, $180 million to $190 million for our revenue for Crysvita. We won't provide projections for Dojolvi. It's doing well. Until we get enough quarters of experience behind us, just like we did with Crysvita, and then we'll begin giving forecasts for the program. It's just launched recently. We have a very strong capital position. We obviously did a fundraise in Q -- in the last quarter and was raised about $435 million in net proceeds. But with the some proceeds from a sale, part of our position in our tourist, it puts us in a position of having $1.2 billion cash. So plenty of cash to fund operations well into the future. Now I think if you look at what's going to happen in 2021 and previewing that, you can see it here on our clinical milestones. With the gene therapy, there are multiple milestones, mostly getting into Phase III in clinical trials running. We'll also provide some update certainly on longer-term Phase I/II data for the 2 programs already have clinical data. For our, we'll provide updates on resuming the Phase I/II for Angelman, which is a big issue that we have to work for, and we're confident we should be able to get that done. That will happen in the first half. We'll start getting more data again in an altered regimen. We'll update the data later in the year from that resumption of the study. We're also filing an IND this year for our first mRNA/LNP, which will happen here in the first half, and we could have some data later in the year. Now setrusumab is a new product we put in our protein biologics space, and we'll expect to initiate a Phase II/III study late in the year. So you can see numerous catalysts, first half, second half both in trial progress as well as data coming forward in the company. I'll dive now deep into a few other of the specific programs of interest. Setrusumab on Slide 9 is the -- first one we'll talk about is a deal we just recently did with Mario Pharma and is a program they had brought in from Novartis, and we're working on developing this antibody for osteogenesis imperfecta. On Slide 10 tells you a little about osteogenesis imperfecta. It's a defect in collagen, the results in significant bone weakness and, which results in fractures and deformities and stiffness and pain related from that. And so it's a very significant bone disease. There's really no approved products. There are some things use off-label. But the key problem in this is understanding that we, not really a defect in collagen weakness. It's really a defect in over metabolizing of the bone related to the defect. So the defect in OI causes your body to a resort bone and to try to fix the bone, but it can't fix it because it doesn't have the ability to do so. What we've found in looking at this and what data show is that if you could simply increase bone formation and reverse the excessive bone resorption, that this should can improve bone strength even with an abnormal collagen and achieve improved fracture prevention. This has been done in multiple animal models, and it's been done only in some nonclinical work we've been doing ourselves. And what we're seeing now is that the Setrusumab in 90 patients in Phase II show have shown some very nice data, which I'll show you here in a moment. But it's this bone remodeling, now top bone modeling, it's really at the core of these, not necessarily just the weak collagen. And that insight gives the opportunity to change the future for osteogenesis imperfecta by improving bone production, which will help reduce bone weakness. On Slide 11, talks about some of the Phase II data that was developed by Pharma. It shows 90 patients, a very substantial set of patients, were given monthly doses for 12 months at 3 different dose levels. And what we were able to show is that bone mineral density improved substantially at both -- in both types 1, 3 and 4 in OI. And it was dose dependent, and it was across different anatomical sites. So it was a very substantial amount of bone, and we think this is a very important improving bone strength. It clearly showed improvement in bone production through the markers for bone. And our expectation is to see improvements in bond strength differences over time. There's a trend to fracture improvement. The study wasn't large enough where I didn't have enough people at the right dose and for a long time. But we feel confident that the improvement in bone density based on everything that's been done in animal work elsewhere will translate in improved fractures. The safety profile, we think, was well tolerated at this point, and we feel very good about the potential to change the future for OI. On Slide 12, we talk about the Phase II/III study and that we're planning, which will help us evaluate dose in pediatrics. And then once we get that clarified, we'll translate into a randomized controlled study in looking at fracture reduction in bone marrow density. The study will take some time in order to establish enough fracture events in order to look at fracture reduction. We're still working going to work with regulatory authorities this year and get to a clinical trial later in the year. And then we'll work on a plan for adults as well. But the pediatric population will give us, we think, the best avenue for approval for the product. If we move forward onto the next program, GTX-102. It is, of course, a very exciting program and related to a deal we did in 2019 with a company called, which was basically founded by parents of Angelman, who put together a development program. And we're very successful in creating an antisense for the treatment of Angelman syndrome, labeled GTX-102. On Slide 14, we summarize a little bit about Angelman neurogenic with a wide variety of manifestations. A very severe -- it's a very severe unmet need. There are no specific treatments for Angelman syndrome today. And what we're looking at is using an antisense alginate to activate the expression of a missing protein UBE3A in neurons. And we believe based on our analysis that the antisense strategy is really the best approach to turning on endogenous UBE3A production and potentially improving the clinical condition of patients with Angelman syndrome. We've shown even at low doses in an nonhuman primate, down to 0.5 or 1 milligram. We can get significant knockdown. And the science behind the Dr. work that led to the scarf this particular, we think, is superior to others, we believe, a very important part of why we're seeing so much potency. Slide 15 is a summary of some of the data has been shown in the 5 patients treated to date. We've shown that all the patients were either much improved or very much improved and that multiple domains were improved across patients, particularly ones that were abnormal. And we're very impressed with the quality of that data and the importance of that data. It was further supported by data from other endpoints as shown on Slide 16, which are done by other observers and quantitative whether it's the Baileys done by psychologist, done by the caregiver or EEGs or other electronic means like the, which showed, again, improvements in functioning these patients, which were important supportive information. So we feel, based on the data we have is a broad multi-domain benefit in these patients. However, it's early in its 5 patients. Importantly, though, we also saw a safety event of lower extremity weakness in all 5 patients. And we've talked before about this event in detail. The program we do -- it was and is on clinical hold. And what we're doing right now is we've done an analysis of everything that's happened, provided a submission FDA, and we're looking forward to seeing this going forward. Now problem we've seen is completely resolved in all patients. So it is reversible. And therefore, everything we learned about it suggests it's simply a local contact issue has nothing to do with the efficacy. It's a local contact issue. The substantial other data we've done shows that you don't see this in nonhuman primates at all and the drug -- the GTX-102 has an excellent safety profile, with regard to tissue. So we feel comfortable with the safety the drive, and we think this is something that's more about local contact and its effect on the tissues, which we think can be improved through simple means. We know the clinical improvements now have lasted up to 5 months from last dose in these patients. So a very substantial long effect size from -- for these patients on the ASL. We've submitted now substantial information men in the IND, includes all this information here, which basically tells us that the drug is safe in nonhuman primate that treatment effect is substantial, what the FDA had not seen. And that the safety effect is clearly highly localized to a particular anatomical area and that, that area could be improved through the use of amended dosing administration just to reduce the amount of contact time of drug and local concentration. We believe that's solution. And it's rare that you have that simple of a solution in front of you, but we're confident that this is a solution that will help these patients and allow us to achieve the efficacy we're seeing without having the effect of the local safety issue. In addition to the working with the FDA, which will be happening this -- right this quarter, we are also looking at -- we have already an active CTA in Canada, and we'll look to opening sites there with an amended protocol. And we're looking at adding some additional sites. So given the efficacy we have, we want to proceed for, broaden the program and put us in a position to move more quickly ahead as we advance and to allow us then to move into a larger cohort and ultimately set up a randomized controlled study for this program. We're excited about the progress management, and we look forward to getting back to dosing in this first half. I'd like to talk now a little bit about the gene therapy programs. Our -- if you look at Slide 20, you can see the basic construction of the gene therapy overview. We have a number of programs, 3 clinical stage programs and a couple of nonclinical programs that are the core of the value drivers for the franchise. But in addition, we have this developing HeLa PCL manufacturing platform that is showing great value, both for buyer in the program, but Wilson as well for us. And now with the new version of it, brings us potential to look at products like for Duchenne, for example. With that platform, we're able to do partnerships, including the partnership with bar as well as the that we did with Daiichi Sankyo, in both cases, taking advantage of the platform to generate value for us, whether it's in product revenue or potentially in revenue for the technology. And we think it's a big part of the total valley story around our gene therapy platform. If you look at Slide 21, you can see our gene therapy for GSD1a. There's a defect -- these patients have a defect in glucose release, they're missing the enzyme required to release glucose from the liver. And in these patent that you end up getting is severe hypoglycemia, but to avoid hypoglycemia, they're all given the large amounts of corn starch every day. About 1 pound of cornstarch a day divide it into a slurries that they take every so often. It's very burdensome, it's very difficult, and it is an important part of their lives. With the treatment, we can see a substantial reduction in the need for cornstarch. And this is just a picture shown here on Slide 21 of 1 patient who had a 75% reduction in cornstarch and how much cornstarch he had to pack for a 10-day trip before he got the therapy and afterward, how important and transformational and is for patients. If you look at the latest data on 22, we show now extension data. The first cohort now is actually cross 2 years into the third year. And you can see excellent results of one of the patients now 100% off cornstarch. Very nice results and really improving metabolism and showing durability of effect now going into the third year, in fact, continuously improving all that time. The other patients from the earlier cohorts also continuously improving over time, including patient 7 from the first cohort now has achieved 100% cornstarch reduction at just after week 52. Looking at the durability from the long-term data, it's very strong, and we're very impressed with how cornstarch reduction is translation to the clinical benefit of our patients, including weight reduction and other factors, which we put out recently in the release. Now let's move on to where we are in the regulatory status. For GSD1, we did have our FDA and EMA meetings. We got good feedback, great constructive. We finalized and design endpoints with regulators, and we should get the first patient enrolled here in half -- first half '21. We're currently operationalizing the study. The change we've made -- we went from 40 patients to 50 and randomized 1:1 to make it a little larger and to give us more power and also to address questions about the size of the study. With regard to duration, we've stuck to the 48-week duration, and we'll use our longer-term Phase I/II data and any crossover data or longer-term data from the Phase III to help support the durability argument. But if you look at the Phase I/II data we have, it's pretty clear, not only the durable, but patients continue to improve the longer they stayed on the gene therapy. The primary endpoint will be the reduction in their critical oral glucose replacement therapy, the cornstarch. But while they will have to maintain glucose control by the continuous glucose monitoring. That combination allows to say, look, we're maintaining good glucose control, we're improving it. At the same time, reducing the critical need for oral glucose replacement therapy via cornstarch. That's the DTX401 program. If we move now on to the AAV for OTC program, the program that's been in the clinic for some time. Basically, there's a defect in ammonia detoxification via the urea cycle. You need to get rid of the money because you make it whenever you break down proteins into amino acids and which generate this ammonia. The only curative treatment, liver transplantation, but most patients basically or ammonium scans in a very strict protein-restricted diet. It's tough to maintain. Patients can do well, but they still will have crises and these crisis, each one can be associated with significant neurologic impairment and potential lethal at times for patients depending on their situation. The program now in Slide 25, we've had treated 12 patients -- 9 patients that have 6 of the 9 have had response, 3 complete responders that are off all drugs in diet. And the 3 other responders have still on ammonia. They have been tapering, but during the COVID, it's been hard to do the tapering because they're -- we're unable to come to clinic. But the 3 other responders continue to be responders and have tapered their medications and diet. The response seems good so far with the earliest responders out, 2 to 3 years post-treatment and continue with good ammonia control without any diet or drugs. So we feel very good about what we're seeing in durability. The prophylactic steroid cohort, which we've treated 2 of the 3, which help us determine if we can use prophylactic steroids as a safer, more efficient way to manage the inflammatory actions to the gene therapy. And so far, this has gone well. As well as it did in the GSD-3 -- GSD-1 program as well. So we feel comfortable about prophylactic steroids as a simple approach to improving the efficiency of the process of starting gene therapy. If you look now at Slide 26, on regulatory status. We have met with the EMA and had, received a lot of good comments that we could work with, and we're adapting to. The end of Phase II program with the FDA, unfortunately delayed to Q1 was not able to be conducted in Q4, and we still expect to enroll in the first patient in the second half. So it's somewhat delayed from the original plan, but not too far off. We plan now to run 50 patients randomized 1:1 to improve the power of the study, and we'll be comparing ammonia -- the change in 24-hour ammonia before between the 2 groups. We're still sticking to a 48-week duration. We do have longer-term data that we think will support durability. And we hope to be able to provide that longer-term data to support long durability while using 48 weeks ports of data from our Phase III for the filing. Finally, let's move on to the Wilson program in IND with file. We're working with the FDA on finishing, getting that ready for activation and our setting and operationally up a study that will be a single pivotal phase I/II -- Phase I/II/III program, which we'll provide more details on in the near future. But we feel very comfortable about the ability of this gene therapy to take inflamed liver, restore normal liver function to achieve ceruloplasmin excretion into the bloodstream, which is the normal copper metal a pathway for the program. Finally, let me touch on Slide 28, the Hem A program from our partner, Bayer, it's been going very well. They have a number of patients now with fairly long-term stable Hem A levels. It's still a relatively small program, but the data are very encouraging, achieving curative effects on Factor VIII production while appearing to have stable longer-term expression rather than peaks early and then declines. We'll continue to monitor the work they're doing on the hem a program. If you put that all together with everything we have, and you look where the company is today, Slide 29, 4 approvals in our first 10 years, which, of course, is an accomplishment of itself, but to have in play now, the gene therapy franchise with 3 products in the clinic entering the pivotal space, a program for Angelman syndrome with exciting Phase II data, osteogenesis imperfecta program entering a pivotal study this year and a new IND for an mRNA/LNP. I think you can say we're a very sophisticated and broad company diversified across both indications and modes. If we put together the larger indications in front of us, in addition to the programs that we have in hand puts us in a position to have a rapidly growing revenue growth as we cross approvals in these indications. And we think we're set up for a very good next 5 years for the company with the build-out in the pipeline we've achieved so far. So the big story is Ultragenyx a commercial company, a diverse rare disease program, the gene therapy platform, mRNA platform and I think, a tremendous future ahead of us. And I want to thank you for your time today. Slide 30. Thank you so much.

All right. Terrific. Thank you, Emil. And we'll now move on to Q&A. And just as a reminder, you can submit questions via the conference portal.

And I guess, I mean, there's so many things that we could potentially jump here. Well, it's amazing how much it's broadened out. I do want to start off maybe with GTX-102 in Angelman, we just get a ton of interest in this one. So maybe just to begin, you can highlight why you believe it can maintain a promising efficacy that you demonstrate in the top line while still overcoming some of the safety issues with what sounds like some simple dose reductions in physical maneuvers?

Well, we have more data now from the repeat dose data -- repeat dose nonhuman primate data GTX Otosan to that being showing that as low as 0.5 milligrams up to 1 or 2 milligrams provided in 4 or 7 doses can adequately knock down the antisense, including 1 milligram being nearly sufficient as potent as higher doses. They weren't aware of how potent that was and that, that level was achievable, but now that's consistent with what we saw in the clinic. If 1 milligram in a nonhuman primate is equal to 10 milligrams, that's consistent with the benefit we've seen at 10 milligrams and makes sense now as to why the efficacy was happening at a much lower dose than expected. So we feel confident mechanistically that the drug at these doses works. And when it's below the 20-milligram dose level, we feel we're below the threshold though that appeared to create the problems that we observed. And so that's kind of the basic thesis around the dose. We know from nonhuman primates that when you do this without Trendelenburg and without a flush, you see threefold higher concentrations locally than you do in the brain, where you're getting the treatment effect. So the question is, can we simply decrease the contact time and the concentration of drug locally and get the drive the mix by moving it granularly where you could achieve mixing in the mixing chamber called the Cisterna Magna. So the simple things we think is if we lower the dose, we think we still can get adequate knockdown. And by reducing local conduct time through the positioning and the flushing, we think we can move the drug toward the mixing area of the CSF, get it mixed and distributed the brain and achieve both improved efficacy by delivering the drug more efficiently north and less safety. It's very few times, Cory, where you have safety and efficacy, distinctly anatomically separated. This is why this is a very simple situation where the administration technique by itself and the dosing can actually alter what happens. And we feel confident that we'll be able to get that done.

So what are the gating factors then to getting this all restarted?

Well, we've submitted a substantial with the FDA, which includes a lot of information we weren't aware of yet, including detailed safety information for all the patients and their efficacy was they hadn't are seen in writing. And in addition to that, we've added in more nonhuman primate nonclinical data in the chronic tox program, which showed a clean safety profile in multiple doses, even higher doses and repeatedly showing that the GTX12 is not a toxic linaclotide, is actually has a very safe profile. Therefore, I think that should Ingenero confidence. And based on that and other tests we've perform, we feel confident we can show them that the simply change the administration strategy and the dosing will be sufficient to reduce the contact exposure time. Given that the treatment effect, the event was reversible completely, we think that does lower the risk level and given the profile of the oligo and the repeat just programs was safe. We feel good about the potential of getting through this discussion with the agency with an appropriate monitoring safety program, the altered administration. We've said that we expect to get back into the clinic first half and to get data here in the second half. We are also opening up sites in Canada. We have an active CTA in Canada, and we'll look to activate sites there with amended protocol. And we'll probably add a couple of other countries to broaden the opportunity to get the program moving forward. And also to allow us to accelerate the program once we get into the clinic and get dosing figured out.

Okay. I guess we'll just hop around here just to make sure we cover as much as possible and the time that we have. So the new data for DTX401 that you announced ahead of the conference. First, it seems like first 9 patients have had consistent responses, which is nice. But I'm hoping you could elaborate a bit on the steroids, the prophylactic steroid cohort? And how might impact hypoglycemia in these patients?

Yes. So the first 9 -- if you look at the curves of all, they look very similar. It's -- they kind of really do overlap, although the cohort 3 with steroid deployed only 2 weeks after the dosing did better, we think, in terms of the speed at which they responded. And that's part of the because maybe enhancing expression. But we feel very comfortable that it was safe to do the steroids. We've treated now 3 additional patients with steroid cohort. They have not had safety issues was doing that. It certainly can induce and does induce the expression more. And we've, of course, noted early introductions in cornstarch, as you might expect. But we don't see any problem right now with this, and we'll put out more information on the cohort. We feel pretty comfortable that going at 2 weeks after goes versus just before the dose, it's not a dramatic difference, but we'll make it a lot easier to in the clinic just to put everyone on it instead of doing monitoring as a tool for triggering.

So that would be the plan then for the Phase III study?

Put them on securities at the time of dosing, keep them on steroids for the period at which we would expect to see liver inflammation related to the gene therapy and then wean them off it steadily over time. And -- so it's not so different from what was done in cohort 3. It's just 2 weeks earlier.

Right. Okay. All right. And then for the other program here, DTX301, another encouraging update for that as well for the 6 ongoing responders. Have you learned anything from the 3 nonresponders in terms of differential baseline characteristics or anything like that, that maybe didn't make them ideal participants or conducive to treatment?

No, nothing specific. I think, of course, there could be a factor of just the dose because we think we got 3 responded when we get up to the high enough dose. When you look at the small -- the first cohort, like we had the 1 patient, he was heavier, so he did get more drug. And the 2 first responder were male, so -- and they were a little bit heavier. So that could be a factor, but we haven't really, I would say, definitively shown what the issue is. But I think we're comfortable that the cohort 3 dose level that we're able to achieve responses in all patients.

Okay. And then on the program in OI that you talked about in your presentation. And maybe just set the stage a little in terms of what drew you to this and to this partnership with Mario?

Well, we've been interested in OI for a while. I mean since we got into XLH, we knew there were a lot of patients. I'm very familiar with it as a clinician and medical genetics. And so we've been looking at it for a while. We actually been running a nonclinical project that's under the radar, we don't disclose. That was giving us some insights in the OI, I think that made the product a good opportunity. And that insight was that it turns out that the weak collagen is really not as big a factor in the weakness in the bone as is the bones abnormal remodeling price response. That changes your mindset then on what you're trying to do. Are you trying to fix the college mutation? Or are you trying to fix the body's response. If you understand that, then you understand why something like can have important and important and profound response because it's simply turning on bone anabolism that's under -- it's underperforming and turn on the bone production even with bone with abnormal collagen is much stronger than not enough bone and altogether. And so in animal models, it's quite profound. You can actually almost normalize bone strength by simply just making more bone. And it may seem kind of trivial and simple, but it is that even with abnormal collagen, the bone -- more bone will be stronger. And the data that they've shown in show that, in fact, in both type one, type 3 and type 4, they achieved an 8% increase in bone marrow density in a 12-month period, which is really substantial and profound compared to others. It's substantial improvement in bone marrow density, but it shows you that in OI patients, that's 90 patients in a dose-dependent manner, you can achieve relatively high increase in bone moral density. We believe in OI, that will translate into fracture prevention. They showed a trend improvement in fracture. There just want enough fractures in the study to be able to show that. But we feel comfortable that if you can alter the production of bone that you will actually treat was really causing the problem in OI, which is too much bone breakdown and not enough bone production.

Okay. When you think about adults versus pediatrics, is there anything fundamental to OI in pediatrics where you would expect kind of divergent results as you go into that segment?

I think mechanistically, is gross and work the same. The question is how the bodies response to that effect. So impedes the bone was just faster and better, and therefore, we'd expect the response to be the same. We are going to explore the dose and make sure we get the dose right, but we expect that response to result in even more effective bone production. And it's similar to what we saw in XLH, if you remember, we did the pediatric seems a very nice effects. And it also saw good bone effects too, but they take a little bit longer to develop because bone metabolism just slows down as you get to adults. So the combination of pediatrics and optimized dosing with claros and I think will show a substantial improving BMD. And those patients get the most fractures, they have the most need and we can do the most benefit. And so as usual, in our strategy, we try to focus on the highest unmet need segment to drive the main thrust of drug development.

Okay. Then on UX701 and Wilsons, can you talk a little bit about this seamless Phase I/II/III study. And how you progress from kind of 1 stage to the next?

Yes. So we've heard from the Head of about -- Peter Marks about the desire for us to look at more efficient models of drug development. We've talked about Phase 1/II recent design. So we took them up on that idea. The key to that is you have to evolve commercial manufacturing before you start, you can't be evolving manufacturing. So we took the time and developed the commercial manufacturing, 2,000-liter scale, highly productive, high-caliber manufacturing, to allow us to get in the clinic and we move quickly ahead. The basic design is a Phase I/II section where sequential cohorts of patients will be randomized to drug the placebo and we'll look at the dose response that we see in those patients. That they entered that through an interim look, we'll understand what the dosing is looking like and then proceed to randomize to that dose cohort going forward into the Phase III portion of the study without having a regulatory step. This means we've agreed to the FDA with the primary endpoint is we've agreed to the approach in the design and other endpoints, all of its agreed to upfront and the manufacturing agreed in order to set up to do that, but the idea that you enroll, learn, get the result and move right into Phase III without a step or a dead period where you go back and talk to authority. So we think that will cut a whole year off the development time line and put us in a position to move quickly ahead toward a pivotal study. The platform, though, is really important in the story because it gives us scale right upfront. And all programs going forward, we'll start with Hela. In that situation, we completed 1 run of commercial scale 2,000 liters. It will be enough to treat 30 patients in the program. And it's just the level of productivity and ability to produce product, I think, is so much greater that will allow us to enroll and move this program promptly ahead.

From a cadence of data update or perspective of the cadence of data updates, how would you envision kind of publicly disclosing what you're seeing in that as you go from kind of 1 phase to another?

When we complete the Phase I/II and we've made the dose determination, we would expect to release some information about where we're at, but we have to release it in a way that doesn't harm the validity of the study. But we would expect to put out some group information about the efficacy that we're seeing and the steps forward. We just have to think carefully about how to do it to inform, inform investors about where we're at on the program and why we're proceeding to Phase III. But at the same time, not harm our ability to interpret the data later.

Okay. And we're seeing a lot in terms of manufacturing know-how and the importance of it when it comes to gene therapy and cell therapy. And you've mentioned the Hela platform quite a bit in this talk. Your plans to kind of continue to do or potentially look at other deals like you've done in the past, these nonexclusive arrangements. Or is this something that you look at is, at this point, with the capital you have, keeping this in-house and having a more of a proprietary competitive advantage for Ultragenyx?

Well, I think we want a little both. I do think there's some value in doing another partnership, generating capital and potential upside for more products, and we can develop ourselves. I do think while we have a proprietary HeLa platform, it's not impossible to develop your own, just takes a lot of work and line development, a lot of combination of know-how as well as patented issues. But we would look to do potentially another deal of that type. But to your point, we wouldn't necessarily just hand it out to everyone as we're going forward, but we do think another partnership would enable us to gain more upside from the technology platform. We are continuing to evolve it, and some of those evolutions do involve new patented elements, which I think will become critically valuable in this field, particularly the HeLa 3.0 changes, which we've talked about last year at ASGCT. So I think we want to do a little of both. We want to gain some upside, but we also want to keep it into a close group of people who are connected to us.

Okay. And then final question here before we're out of time. I mean it's pretty amazing to see how much broader your pipelines become over the last few years. So when you think about business development from a product-specific point of view, how much are you still out there kind of scouring the landscape looking to bring more assets in versus -- you have a lot in your plate right now and kind of deal with what you've got?

Well, right now, we will have 6 clinical stage programs, which is in our sweet spot of 5 to 7. So from a development stage program, we think we're pretty full of what we need to do within all the segments of our business, plus some nonclinical program still coming forward as well. So we're pretty full. We are looking at and have had interest in working with other companies regarding commercial stage programs, particularly in our excess footprint since we're one of the few sort of smaller rare disease companies that has a global footprint. And as other rare disease companies have gotten bought, left us in a position to be a good partner with people with commercial stage programs. So we'll look at potential commercial stage targets. But right now, the clinical state pipeline is pretty full, and you'd have to have something truly compelling to make a step forward at this point.

Okay. Makes sense. So that's all we've got time for. Emil, thank you very much. Really appreciate your perspective, once again, and good luck at the meetings the rest of the week.

Thank you, Cory. Thanks for having us.