Good morning, and welcome to the Jefferies Global Health Care Conference in New York. My name is Nick Pecora with the Jefferies Investment Banking Team, and it is my great pleasure to introduce Javier Swartner, CEO of Spruce Biosciences.
Thank you, Nick, for the intro, and thanks to everyone for being here. So it's a great pleasure to be speaking with you today and telling you a bit about Spruce Biosciences. I'll be making some statements along the way. I'll refer you to our SEC filings for further reference. So, our flagship acid is a tralicinidase alpha, which is an enzyme replacement therapy currently being developed. It's a compound, it's an ERT that gets delivered inside the brain through the intraservular ventricular route, and it's using a surrogate endpoint approval pathway, hopefully that will result in an accelerated approval of a product. We've demonstrated a very profound effect on this endpoint reduction with normalization of both heparin sulfate and heparin sulfate non-residual ends, which is a more specific measure in MPS3B. This approval pathway was recently evaluated by the approval of Avlaia, a compound that Denali is currently commercializing for MPS2, another neuroneopathic disease. The disease is terrible, MPS3B affects children and creates incredibly disability that impacts not only the patient but also the caregivers and family and all that. There's currently no approved therapy for MPS3B. We've gotten all sorts of designations from the FDA including breakthrough designation which was granted in October of last year and have rare pediatric disease designation which, if approved, will allow us to tap into the PRV opportunity. We also have a monoclonal antibody currently in our pipeline. It's a MAP for congenital adrenal hyperplasia. It binds CRH. It's a CRH ligand. And it's a validated mechanism by virtue of the approval of cronestophon, a drug by Nercrin a couple of years ago for CH. So I'll be speaking today about the TRT program and not the CH program, but if there are any questions, happy to address them. So the market opportunity is quite large. We've been very conservative, I think, in our estimates on the epidemiology, but we project the incidence to vary by region, but to be between 0.5 per 100,000 to 4 per 100,000 life births that could give us about 450 patients in the US 500 in Europe 1800 in Asia Pacific and 300 in Latin America or 350 in Latin America non-attenuated San Felipe type B which is a type of form that we're seeking to address has a very short lifespan with most patients living roughly around late teenage years, around 18, 19, is concentrated in areas, is an autosomal recessive disease, so is passed through two genes from the parents with each child of an affected family having a 25% chance of getting it. It's highly concentrated in areas where there's consanguinity, and that results in higher rates in southern Europe, Turkey, Greece, Saudi Arabia, Brazil, and a few other countries. So assuming that we can address half of the prevalent patient pool, we can, you know, we're probably going to be hitting around, you know, five years post-launch, around 250 patients treated, with estimates that we might be able to address a total U.S. pool of around 500 patients at peak there are many other comparators that we can use to benchmark a potential price this is not yet to provide guidance to the street on on what we think the pricing might be but given that our product isn't weight based and that it is given as a fixed dose inside the through the interest cerebral ventricular route we've mapped on this slide compounds that on the far right column are tend to be weight based or body surface area what base with upper bounds of cost pricing per year that range between 1.3 and 2.8 in 2.8 so we think that our price on the lower end of 1.5 and on the upper end around around 2.5 with an anchor around 2 might be suitable for this type of disease. As I said earlier, NPS3B is a devastating disease. Kids and affected families have to deal with a child that develops semi-normally up to the age of 3 where they start missing developmental milestones, peak their behavior and cognitive They function at around three years of age, and then they decline. They lose brain function, cognitive function, around eight to ten years of age. They've lost the ability to speak, to ambulate, to communicate, to feed themselves. They become bed-bound, eventually need feeding tubes, tracheostomy tubes for breathing, and they demise from complications of any type of chronic neurodegenerative disease, much like Alzheimer's patients. So we're trying to revert that route, and the way we revert that route is by removing the glycan that accumulates and builds up in the brains. Heparin sulfate, which is the glycan that most likely accumulate, given the enzymatic deficiency, builds up in lysosomes. The enzyme actually, nylalune, anacetylglucosaminidase, which is a missing enzyme, sits in lysosomes And heparin sulfate just builds up and accumulates in that space, which causes inflammation and neurodegeneration with the advent of therapy that gets administered straight into the CSF. that drug, the enzyme penetrates into the neural cells through the drug construct, which is nagloenzyme, amino acid linker, and a truncated IGF-2 molecule, and it is primarily through the truncated IGF-2 molecule that enables the neuronal penetration. And that sets aside, frankly, this compound relative to other ERTs tried in the past and failed for MPS3B. So we've designed, actually, Biomorane, and the prior sponsor, have put together a development program that encompasses a feeding study, which is a 902 study that brought in patients into the 201 trial, which is the treatment trial. We treated around 22 patients for 48 weeks, and then those 22 went into extension studies. So we have about five years' worth of clinical data and biomarker data and safety data on those patients. The efficacy and safety is contrasted relative to the 902 program primarily, which is a natural history study conducted as well by Biomarin prior to our acquisition of a product. which allow us to, you know, in a proper way have a very valid external control arm to contrast our clinical benefit. We've shown very profound reductions of biomarkers and, I think, fairly strong clinical evidence of benefit, which I'll show you shortly. Currently planning a confirmatory trial, we are assuming an accelerated approval under under this, under our approval framework or FDA review framework, and as such, we would require a confirmatory study that's agreed upon with the FDA at the time of BLA submission, which we have achieved. So we currently have a 14 patient trial, seven per treatment arm, randomized control in nature. where patients will be treated for five years with a BSID, which is called the Bayley Cognitive Raw Score, as our primary endpoint for the confirmatory trial, and which will support full approval. It's a five-year trial. So going back to our clinical data, our biomarker data is very profound. On this slide, on the y-axis, you have the heparin sulfate in the CSF through five years of follow-up. And you can see that at most time points, the biomarker was within the limit of normal. This has not been achieved by any other therapeutic, any other ERT, actually, to treat any neuropathic MPS, not just, I mean, there's none for MPS3B, but when you benchmark the effect sizes that we're achieving and seeing are very, very profound. And this is also confirmed by benefit on a more specific biomarker, also part of the HS family, but measuring the non-residual end, which is the kind of stopping point at which the enzyme stops chopping because it's missing. So very consistent with the data on the overall HS. When one looks at the benefit on cognition, looking at the full approval endpoint, which is what the FDA wants to see in the confirmatory trial, we also see significant benefit. This data was shared with the FDA as part of our October 2025 submission for breakthrough designation, and I think had a profound effect on the granting of the BDD. day. And as you see on the purple line at the bottom, patients on the natural history arm decline usually around three, four years of age, all the way down, losing brain function and cognitive function until the end of our follow-up, which was 11, and then they just plateau and remain flat throughout. We've looked at a number of things derived from From another type of a very important questionnaire called the VAPS or the Vineland Questionnaire, Denali is conducting their confirmatory study using the Vineland Questionnaire and not the Bailey's Questionnaire. I guess that was an agreement they reached with the agency. But we see, again, a very similar degree of benefit on receptive communication, expressive communication, gross motor skills, and fine motor skills in the context of violin, we continue to assess endpoints from the violin that inform a few areas that are very important by caregivers of patients with this disease, mainly ambulation, feeding, and other type of measures of well-being, right, so, and those data are being analyzed and will be presented to the FDA as part of our BLA to demonstrate meaningful functional benefit in additional biomarker benefit, which I think further reinforces our story. In addition to the clinical data, we have imaging data showing that after six months of treatment in the 201 study, brain cognitive gray matter volume, which is the space or the area of the brain that suffers the most from neurodegeneration, and this disease remains stable. This is in contrast with what you see in natural history patients, where there is an ongoing decline in brain degeneration. We didn't measure cortical gray matter volume or MRIs in our 902 study, but we have an external control trial that actually followed patients over time, and that's very informative, and we're including those data in our BLA as well. In addition to the brain effects, we also have... So let me give you some context in terms of how the drug gets into the periphery. So through the lymphatic system, the drug escapes the brain and gets cleared. The lymph, the CSF typically circulates about four times a day, and that allows for the compound to actually reach the systemic circulation, which is a very important component because over time, If we extend lifespan on these patients, what we would want to achieve also is clearance of heparin sulfate in the periphery and be able to address the potential future cardiovascular, lung, joint, GI complications of this disease, which we're not seeing because the biggest comorbidity is the brain. So we've seen normalization of liver and normalization of spleen sizes, which denote promote systemic treatment, systemic clearance of heparin sulfate. From a safety point of view, frankly, not much there, pretty much what one would have expected in the context of a compound that's delivered through the ICV device, fairly well tolerated, no meaningful hypersensitivity reactions that we can attribute to compound, generally well tolerated. There's usually anti-drug antibodies, some of which are neutralizing antibodies, but to a low degree, and given that antibodies typically don't penetrate the blood-brain barrier too much, there's no reduction in effect size as measured by heparin sulfate and heparin sulfate NRE in patients where neutralizing antibodies were detected. Currently, the company is well capitalized. We announced close in the quarter with $107 million of cash, which allow us to advance our program and have enough cash beyond our projected approval date. We forecast submitting the product at the end of the year in Q4 and obtaining approval under an assumption of a prior review by a little part of next year. With that, I'll stop my presentation and open it up for questions, if there are any. Yes. So we're currently in the process of identifying patients. The projections that I showed you earlier in the deck are based on publications and on a claims database analyses that allow us to get some insights as to the potential projected number of patients. We've hired, we're currently in the process of hiring and expanding our commercial team, but have already hired a chief commercial officer, a head of commercial operations, and head of market access. and our chief commercial officer Dale Hooks was frankly very much responsible for the patient ID efforts that Riata took that took place for under for Riata for Fredrick's ataxia and be able to you know get the product approved with about 300 patient forms in the patient hub in about a thousand patient forms four months after the launch of a product in a you know fairly uncommon and rare disease. Dale has a very strong track record of rare disease commercial launches, and his top priority is actually doing exactly that, identifying patients that are going to hopefully go on treatment. We're also in the process of initiating an expanded access program, which we hope to have in place in the second half of 2026, which will allow allow us to segue patients from the trial into commercial product when commercially available. We are partnering with the patient foundations to be able to get that trial enrolled and They've been very collaborative and super supportive of the effort, and yeah, we'll be updating the street and on our progress made around patient ID in the future. I see no further questions from the audience. Thank you so much for your attention and looking forward to updating you in the future. Thanks so much.