Spruce Biosciences (SPRB) Fireside Chat - SPRUCE BIOSCIENCES INC

Good afternoon, everyone. I'm Albert Lowe, Senior Biotech Analyst. We've had a really great day of fireside chats, and I'm happy to close it out with Javier Schwartberg, the CEO of Spruce Biosciences. If anyone in the live webcast audience has a question for Javier, please feel free to submit it here in the meeting interface. Now, Spruce has been developing TA-ERT, an enzyme replacement therapy for MPS3B, and their upcoming catalyst is the planned BLA submission that's coming up this quarter. So, Javier, can you start by giving a brief overview of MPS-3B and the clinical data that will be submitted with the BLA? Sure, happy to do that, Albert. And thanks so much for hosting us at the conference. been a busy day with a lot of meetings so i appreciate the fireside chat as well uh mps3v is a uh neuronopathic mucopolysaccharide doses i mean it affects primarily the brain of very young children uh incredibly disruptive to families suffering from from this uh condition uh and it results inevitably in demise it's also known as pediatric dementia or children childhood dementia where where children evolve um kind of normally up until age two and a half while still having disease and having glycans deposited in their brains um usually they start having symptoms missing developmental milestones up until age two two and a half, and that's when the quest for a diagnosis starts, which usually comes around age four for this condition, and any effort that we as a company can do to accelerate the earlier diagnosis will translate into meaningful improvements if our therapy gets approved because removal of substrates should result in an ongoing and continued acquisition of developmental milestones by kids affected. So the clinical, this disease evolves. I mean, if untreated, usually kids have a period of plateauing around age of four for about a year and then there is ongoing decline where they lose functions acquired they lose the ability to initially speak then understand they lose their fine motor skills and later on their gross motor skills with that they can't eat they lose weight they need g-tubes they lose the ability to breathe, and they need tracheostomy tubes, breathing tubes, and wheelchair-bound, and then they die usually in the late teenage years. With regards to a clinical package that we'll be submitting along with the biomarker data to the FDA, which in our case is heparin sulfate, which is deemed by the FDA for Hunters, which is another neuronopathic MPS, as a reasonably likely surrogate endpoint of clinical benefit resulting of the approval of their product for Hunters. And also as a supportive endpoint in the label of the most recently approved gene therapy for MPS3A for UV under ultragenics as a meaningful endpoint, right? So we have that piece where we have a very profound effect size, as well as a whole array of endpoints related to clinical benefit that span cognition, adaptive behavior, motor communication, MRIs, and also benefits in the periphery. Because drug administered through our ICV device into the CSF leaves the CSR space and circulates and then clears liver and spleen from accumulations of heparin sulfate. All right, great. So MPS3B is certainly a very devastating and heartbreaking disease. How would you expect TAERT's effects to translate into extending the lifespan for patients beyond the early death that's otherwise expected? I mean, this disease is going to alter the course, this drug will actually alter the course of the disease by removing substrate that's accumulating in neurons, which is known to be inflammatory and neurodegenerative, we will hopefully improve the health of the neurons that have been damaged chronically and preserve the neurodegeneration that will invariably happen without treatment over time. So what we typically see in this type of conditions is that patients are able to maintain neurocognitive function, adaptive behavior function, communication, motor skills, and because of that, live more fully lives and extend life expectancy. We have a number of children that were treated with this disease early on in their tenure, and, you know, they're able to speak three languages, ski, go to regular school, which is frankly unheard of in the context of MPS III. Right, great. And thanks for, again, highlighting those clinical endpoints where you've kind of shown some great data here. now this upcoming BLA submission will be an important milestone for the program so can you share where you are in this process and perhaps there's a current limiting factor or what's next for filing the BLA yeah we've guided to a BLA submission in the fourth quarter and we're on deck to do that things are moving very swiftly and we're very positive that we'll be able to accomplish we've guided. The clinical CMC package is coming along very well. We've been able to complete manufacturing of TS and DP under the PPQ1 framework. FDA had wanted to see the analytical reports from the first PPQ batch that we have made and And we are in the process of completing that analytical report and completing the writing of the BLA. We've been very positively impressed by the most recent MPS3A approval, which was a full approval based on a clinical package that we believe we potentially share. So, we are including modeling data, including a number of endpoints that hopefully will translate into a broader opportunity to further decrease any type of clinical risk that relates to the review of our application, but fairly positive about the effect sizes that we've We've seen FDA very aligned on heparin sulfate as a reasonably likely surrogate endpoint of clinical benefit. And, yeah, I mean, we tick the box on natural history, tick the boxes on the effect sizes that we are seeing on model data, as well as raw data analyses. But I think we have a fairly robust package that will allow the FDA a very thorough review. all right great yeah i i think certainly the clinical data and circuit endpoint data is very compelling and thank you for sharing the details on uh where you are in the cmc process maybe related to that um what do you think is the potential impact from this planned strike at at Samsung Biologics, your manufacturer? Not very large, actually not at all. Samsung typically goes through, or labor unions within South Korea typically go through strikes to negotiate better pricing, better working conditions, better wages. wages, and we've seen that happen earlier in the year and typically happen two, three times a year. The current strike, I mean, in prior years, something has about a 50-50 unionized and non-unionized workforce the current strike is is like like all of the past ones always you know the past ones have resulted in in in resolution of the strikes without things getting to any type of major place something has reassured us like in the past that they have extra workforce that if the strike is to impact the manufacturing of our product, we wouldn't be affected. We already completed manufacturing for drug substance for PPQ-2 and are going to be filling later in the quarter drug product of PPQ2, which is what we aligned with the FDA to include during the review. So, you know, I don't think this is going to have, frankly, any impact, Albert. All right, great. Well, happy to hear the history of kind of resolution there. And it sounds like, manufacturing side, you've kind of got everything you need for these kind of next steps here. Maybe we can circle back to something you mentioned, which was Ultragenyx's MPS3A drug. So, maybe you can tell us more about how your data package compares, and what do you think the FDA considers when they're deciding if an application warrants an accelerated versus full approval? And maybe back it up a little bit and give us a little context on how your registration or how your registrational strategy compares to theirs as well. I mean, I can only speak for what's in the public domain regarding ultragenics. Obviously, the drug was recently approved, so there's no summary basis of approval yet published. But their labeling, their indication was approved in full and based on BSID cognitive raw score, which is exactly what we've collected in our clinical program. The label also in Section 14 acknowledges the benefits that they have seen on heparin sulfate. So, the FDA labeled them on both endpoints. Our package to FDA will include the benefits that we've seen in BSID cognitive raw score, as well as benefits on other endpoints, which will also be presented as model data and raw data. as well as, as we've presented multiple times, the benefits that we've seen on heparin sulfate and heparine sulfate non-recyclable ends. The ultimate decision as to what approval pathway products follow is really up to the FDA. And the situation has been quite mixed, actually. There has been products that have presented or packages that have contained randomized placebo-controlled data where the FDA has granted XR approvals and packages where single control arms relying on external controls for comparison, for clinical data comparisons, where the FTA has granted full approvals. So, I think that when I compare our package relative to what Ultragenyx provided, we have an in-house natural history study initially conducted by Biomarin and completed and reported actually already in the published literature. That study was conducted in a very robust way following GCP practices, which is a study that we're using to compare the benefits that we've seen in our treated patients, including the extension study in our treated patients with very long length of follow-up, both in the treated arm and in the natural history arm. As expected, there are always imbalances at baseline between natural history studies and treatment arms and therapeutic trials of treatment arms. And that's because natural history studies tend to capture the universe of patients so that we can define what is the natural history of patients lying in different age groups. So model data really allows you to, through analytics, to adjust for imbalances at baseline and attribute nods of measurements, right? And so, you tend to, like Ultragenyx did, where they looked at the effect sizes between a certain therapeutic window, we will be doing the same thing in our filing in a way that makes sense for MPS-3b. All right, well, certainly a very interesting case study, and I can appreciate that it's fully up to the FDA when they make this determination. But can you describe how or what the impact might be if TAERT were to get a full approval versus an accelerated approval? Dr. Well, clearly, it will lower the need to have a confirmatory study ongoing. FDA might request a patient registry, which is not uncommon to capture long-term follow-up, Although we have extensive follow-up with our product that supports both durable efficacy and adequate safety, I think it will allow us to speak about the clinical attributes of the product more freely, which will be a good thing when we go commercial by our field team. But shy of that, I don't think there are very many additional attributes. The pathway towards a prior review voucher is the same. And frankly, the need to confirm the benefit is something that we can probably take off the equation and remove that, in my mind, very small element of risk, but nonetheless. All right, great. Well, you know, looking ahead, you know, we're not really far off from a potential commercial launch next year. What have you learned about maybe patient demand ahead of the commercial launch? How has the interest been in this EAP program? And are there any patients that are currently receiving the drug on compassionate use? Yeah, significant demand. I mean, we've put together a website called mps3bstudy.com, where we encourage patients that have an interest in participating in our clinical program, which includes the expanded access program, and at this stage, our confirmatory trial to sign up, as well as patients that are interested, or I shouldn't say patients, caregivers that are interesting in receiving information about MPS3B and or our product, clinical data and so on. So through that, we're identifying, you know, a number of potential families with disease. There's obviously the claims database work that most companies do prior to going commercial. And the paradigm that we all need to navigate is the fact that when there's no approved product for a disease. There is typically no ICD-10 code, so there's a lot of imprecision around how many patients truly have a specific disease. Currently, patients are being coded to an MPS3 code, which is not segmented by either MPS, you know, the most common ones, right, MPS 3A and 3B, and the far less common ones C and D. So we're having to make assumptions as to how many patients are out there. Based on epidemiology, we project around 450 based on the currently existing epi data from many years ago, a registry run by the National NPS Society. Based on our very preliminary work, we identified more patients than that. However, we will not be guiding until, obviously, our peri-launch window on how many patients we have. But there's been meaningful demand. We plan to go and talk to the 15 lysosomal storage disease centers of excellence in the country, continue our work related to claims database analyses. There's a lot of social media work being done by the very large constituencies signed up under CURE San Felipe and National MPS Society, which are the two major patient groups, which are very advanced and in our eyes, very sophisticated, who've actually partnered with us very closely to fundraise, well, they fundraised, and they invested through a pipe tool in Spruce to provide product to the expanded access program. So we feel very positive about the patients that have actually, that we've so far identified. We far exceeded what we need or projected to treat in year one. Ultragenics is approval for MPS3A. will inevitably result in more 3B patients being identified. So that's a good thing, they're creating noise. They will be putting efforts to get newborn screening underway. And the efforts are frankly irrespective of MPS3A or B. So that gonna be very positive for us as well. So all in all, I think really good momentum in this space. with Fayuvi approved earlier in the year, sorry, with Avlai approved earlier in the year, and Fayuvis approved on September 17th. All right. So of these estimated 450 MPS3B patients in the U.S., I was wondering what portion of these you would say are addressable, and along these lines, I know it's important to get these patients' treatment as early as possible, but is there like an upper age where patients may not be good candidates for therapy? There's no upper age. I think it depends. That decision will be made by the physician and the caregiver. The more market research we do with families suffering from this disease, we learned that how much willing families will be of accepting therapy and in assessing whether therapy is being beneficial or not. I think that it is difficult for us with you know normal lives to to to foresee a situation where living with a child that has a very advanced disease would be acceptable but if what we hear from families is that if we can hold progression of disease and keep my child my adult child the way he or she is today that will be an incredible win and I'll be incredibly happy so I think that you know we were likely to see more patients than not trying therapy and some of some will continue on treatment and some will not okay how many new Patients are there each year. Based on the, again, very limited epi, we are foreseeing or projecting a 0.5% per 100,000 live births. And that translates into about 20 patients, 20 new patients per year in the U.S. Okay. Maybe last question here. Maybe you can give us some of the good comps for potential TA, ERT pricing, and maybe what would be a reasonable floor for this pricing corridor. Yeah, I mean, our product, I would say, before I dive into the comps and the estimates around projections, this is a global product, Albert. This disease lives not just in the U.S., but also globally, and the global opportunity may be, in many respects, larger from a patient size point of view. Obviously, ex-U.S. there's a lot of competitive pressure on pricing, and we'll be very sensitive on MFN and all that, But we'll find sensible ways through local distributors and local licensing to make the product available globally. Now, that said, our product isn't weight-based. It's fixed dosing. When you look at the price range of weight-based products, it's fairly large with upper bound for patients that weighed near adult weight of close to 2.5 to 2 .8 for the analogs that we've listed in our corporate deck. We believe that a price point anywhere between $1 and $2 million per patient per year would probably be reasonable. we've had some initial discussions with payers and we'll continue to do that. But hopefully that provides enough of a, of a guidance to, to how we're thinking about, about pricing. All right. All right, thank you. Well, you know, we'll closely follow the progress for this BLA submission that's planned to, that's planned for this quarter. And thank you very much, Javier, for the great discussion. And thanks, everyone, for joining us in our fireside chats today.