Recently, Spruce Biosciences announced that the FDA had granted its lead therapy, tralesinidase alfa enzyme replacement therapy (TA-ERT) Breakthrough Therapy Designation for the treatment of patients with San Filippo Syndrome Type B (MPS IIIB). The share price of the company’s stock closed the day higher by 121.58% to $130.40 per share on the back of this news release. The significance of this is that this designation brings about with it several other bonuses and is likely the reason why the stock traded higher. BTD brings forth the potential for the company to file for a rolling Biologics License Application (BLA) submission of TA-ERT to the FDA for the treatment of these patients with this lysosomal storage disorder.
Another positive that stems from this designation would also be the ability to receive Priority Review Designation upon a BLA submission in place for this enzyme replacement therapy (ERT). The rolling BLA submission is set to expedite the regulatory process by having the submission be done a lot earlier than expected. Plus, it gives it a chance to interact more with the FDA while parts of the application are being submitted on this rolling basis. The Priority Review is important because it cuts down the review time of the regulatory application from 12 months down to 6 months. Should the company have everything in good order, it expects to be able to file the BLA in the first quarter of 2026.
The stock price trading higher as much as it did on the back of this highly positive BTD from the FDA was, I believe, fueled by the fact that the company could seek for accelerated approval (AA) of TA-ERT for the treatment of these patients with MPS IIIB. It all has to do with the fact that a prior meeting Spruce held with the FDA noted that cerebrospinal fluid heparan sulfate non-reducing end (CSF HS-NRE) could be used as a surrogate biomarker endpoint to put it in the position to be able to file on this AA pathway. Furthermore, long-term integration data released a few months back in August of 2025 revealed that this therapy was able to reduce CSF HS-NRE in a statistically significant manner, with a p-value of p<0.0001 over a 5-year period. In other words, patients that took TA-ERT saw a decrease of this surrogate biomarker endpoint by 91.5 ng/ML from baseline.
The end result is that patients were able to reach normal or near-normal levels of CSF HS-NRE. San Filippo Syndrome Type B, or MPS IIIB, is a lysosomal storage disorder whereby patients have a mutation in a specific gene that is supposed to be responsible for clearing toxic HS in the patient’s body. There are several other types of San Filippo Syndrome, and with that, each one has a different genetic mutation that causes disease. In the case of this one, Type B, there is a mutation of the enzyme N-Acetyl-Alpha-Glucosaminidase (NAGLU). Moreover, with Type B there is an accumulation of HS in the brain, and if not treated properly, it leads to cognitive issues and neurodegeneration as well.
The biomarker CSF HS-NRE is classified as the toxic buildup that occurs in a patient’s brain; thus this is why the meeting Spruce concluded with the FDA stated that this surrogate biomarker would be appropriate to signify clinical benefit in these MPS IIIB patients. To accomplish this, TA-ERT is composed of recombinant human NAGLU enzyme (rhNAGLU) and is given to patients via intracerebroventricular injection. Basically, the cerebral vesicles and the purpose of this is to adequately deliver this therapy straight to the central nervous system (CNS) so that it can reduce CSF HS-NRE in the brain. If this therapy is to be approved for these patients, it would be a huge win, because it would become the first potential disease-modifying therapy for them.
Besides the stock price trading higher or the market cap of the company possibly increasing on the back of FDA approval of TA-ERT for the treatment of patients with MPS IIIB, it would also bring forth a Priority Review Voucher (PRV) from the FDA. This is crucial because these PRVs can be sold for $150 million or more. For example, Abeona Therapeutics was able to complete a sale of its PRV and brought in roughly $155 million in cash.
All of this potential that Spruce Biosciences has doesn’t even include another program from its pipeline, which is the evaluation of the CRF1 receptor antagonist tildacerfont for the treatment of patients with major depressive disorder (MDD). To accomplish this goal, the company is currently running the phase 2 TAMARIND study using this small molecule to treat these patients. In order for a person to be classified with MDD, they need to have a low mood state for a total of two weeks or more. Investors won’t have to wait long to see if the company can also advance this program forward because results from this mid-stage trial are expected to be released in the first half of 2026.