Executives from Spruce Biosciences (NASDAQ:SPRB) outlined regulatory plans, clinical data highlights, and commercial considerations for the company’s lead program in Sanfilippo syndrome type B (MPS IIIB) during a fireside chat at Oppenheimer’s 36th Annual Healthcare and Life Sciences Conference.
Program overview and development history
Chief Executive Officer Dr. Javier Szwarcberg discussed Spruce’s enzyme replacement therapy program, referred to in the discussion as “TA-ERT,” which is designed for central nervous system (CNS) delivery. Unlike most enzyme replacement therapies that are administered intravenously and have limited penetration into the brain, Szwarcberg said this therapy is administered directly into the cerebrospinal fluid (CSF) via intracerebroventricular (ICV) delivery using an Ommaya reservoir. He said this approach is intended to address the profound CNS involvement in neuronopathic forms of mucopolysaccharidoses, including MPS IIIB.
On the asset’s corporate history, Szwarcberg said BioMarin out-licensed the program as part of a strategic pivot toward other products, including ROCTAVIAN and VOXZOGO, rather than due to deficiencies in the therapy.
FDA interactions and planned BLA timing
Management said Spruce recently held meetings with the U.S. Food and Drug Administration and is guiding to a biologics license application (BLA) submission in the fourth quarter. Szwarcberg described FDA personnel as “super stable” at the office and division levels and characterized the tone of recent meetings as positive and collaborative, with acknowledgment of the unmet need in MPS IIIB.
Szwarcberg said the company sought alignment with the FDA on the adequacy of its data package, consisting of interventional trials and natural history data. He said the agency agreed with using heparan sulfate as a “reasonably likely surrogate endpoint” (RLSE) to support an accelerated approval pathway, while emphasizing that accelerated approval still requires “substantive evidence of effectiveness.”
He also discussed chemistry, manufacturing, and controls (CMC) topics, particularly the timing of process performance qualification (PPQ) batches. Szwarcberg said the company had expected flexibility similar to some other rare disease programs, but described FDA as “lean” and burdened with reviews. He said FDA indicated Spruce could submit one PPQ batch with the BLA, provide a second around the mid-cycle meeting, and submit a third post-approval as a post-marketing commitment.
Clinical data: biomarker durability and functional measures
In discussing data presented at WORLDSymposium, Szwarcberg said patients in trials have generally tolerated long-term therapy, with occasional treatment breaks due to pleocytosis or infection concerns related to the device and administration route. He said that despite prolonged breaks, heparan sulfate did not re-accumulate in CSF among tested children, which he presented as evidence of durable biomarker control.
He also addressed immunogenicity, stating that anti-drug antibodies have been observed, including some neutralizing antibodies over long treatment durations, but said these have not appeared to reduce potency. He attributed this to neutralizing antibodies generally being peripheral and rarely crossing the blood-brain barrier, while the therapy is delivered directly into the CNS.
Beyond biomarker effects, Szwarcberg said the company has observed clinical benefit on cognitive measures, including the Bayley Scales of Infant and Toddler Development (BSID) raw scores, and described BSID as the endpoint FDA has asked to be used for the confirmatory trial. He also cited benefits on adaptive behavior measures from the Vineland questionnaire, including communication and motor skill subdomains, with separation between treated patients and natural history comparators. He emphasized earlier treatment as a key driver of better outcomes.
He highlighted individual patient examples shared at WORLDSymposium, including siblings treated at different times, where earlier treatment was associated with better function. He also referenced a poster comparing siblings where one was treated and the other was not, describing better developmental milestone attainment in the treated child.
Review timeline, confirmatory trial, and financing
During the discussion, the timeline contemplated by the analyst suggested that a fourth-quarter BLA submission could lead to a potential approval decision around the middle of 2027, which Szwarcberg agreed “sounds about right.”
Szwarcberg described 2026 as an important year for the company, citing several expected activities:
- Submitting the BLA and seeking acceptance for review
- Manufacturing drug substance and drug product to support PPQ batches
- Initiating the confirmatory trial, which he said FDA expects to be underway while the product is under review
On liquidity, he said Spruce’s cash runway extends into early 2027, potentially leaving a “small gap” relative to the timing of a possible approval. He said the company has a $50 million debt facility, has drawn $15 million, and has $35 million remaining that could be used to close that gap. He also said Spruce is exploring partnership opportunities in Asia as a potential non-dilutive capital source and cited an existing partner in South Korea, LG Chem, while noting the company is considering options in Japan.
Commercial considerations and other pipeline notes
Szwarcberg discussed commercialization in the context of specialized “centers of excellence,” noting there are a limited number of lysosomal and MPS specialty centers in the U.S., implying a focused physician base. He also emphasized the importance of a “patient hub” to help families navigate authorization and therapy setup.
Comparing administration to BioMarin’s Brineura (also ICV-delivered), Szwarcberg said Brineura can be associated with hypersensitivity reactions requiring pre-medication and a longer infusion time. He said Spruce’s therapy is administered as a shorter “slow push” over five to 10 minutes and that the company has not seen a hypersensitivity reaction to its product in its experience to date.
On market size and pricing, Szwarcberg said the company believes the peak opportunity could exceed $1 billion in sales, citing improved diagnosis and extended life expectancy in ultra-rare diseases as factors that can expand commercial opportunity over time. He also said the product is not weight-based and that its route of administration and therapeutic profile may support pricing “accordingly, but sensibly” to enable access.
Szwarcberg also said Spruce is open to adding additional late-stage rare disease assets in the future that could leverage the commercial infrastructure built for this launch.
Finally, he pointed to potential read-through from other programs in the space, including Denali’s MPS II therapy under FDA review, with a PDUFA date cited as April 5. Szwarcberg said he expects meaningful read-across, given what he described as similar clinical databases and benefit on heparan sulfate.
Outside of TA-ERT, Szwarcberg noted Spruce has another asset in congenital adrenal hyperplasia (CAH), described as a monoclonal antibody targeting a CRH ligand, which the company hopes to “kickstart” during the year, with additional updates to come when ready.
About Spruce Biosciences (NASDAQ:SPRB)
Spruce Biosciences, Inc is a clinical-stage biopharmaceutical company dedicated to developing therapies for rare endocrine and dermatological disorders. Headquartered in San Diego, California, Spruce focuses on conditions with significant unmet medical needs, employing a precision medicine approach to identify and advance treatment candidates through late-stage clinical trials.
The company’s lead asset, tildacerfont, is an oral corticotropin-releasing factor type 1 (CRF1) receptor antagonist being evaluated for the treatment of congenital adrenal hyperplasia (CAH), a genetic disorder characterized by insufficient cortisol production and excess androgen levels.
