ACER-001 for Maple Syrup Urine Disease (MSUD)


ACER-001 is a powder formulation of sodium phenylbutyrate (NaPB). The proprietary formulation is designed to be both taste-masked and immediate release. ACER-001 is being developed using a microencapsulation process for the treatment of various inborn errors of metabolism, including UCDs and MSUD.

NaPB is approved for people with urea cycle disorders (UCDs) to control their ammonia levels in conjunction with a restricted diet. People with UCDs who are treated with NaPB have been found to have induced branched-chain amino acid (BCAA) deficiency, despite adequate dietary protein intake.1

Based on this clinical observation, investigators at Baylor College of Medicine (“BCM”) explored the potential of NaPB treatment to lower BCAA and their corresponding BCKA in patients with MSUD, a disease where BCAA/BCKA levels are significantly elevated. The investigators found that BCAA and BCKA were both significantly reduced following NaPB therapy in control subjects and in patients with MSUD, although there was no simple correlation between the patients’ levels of residual enzymatic activity with the response of plasma BCAA and their BCKA to NaPB.2 NaPB demonstrated a statistically significant reduction of leucine in all three healthy subjects and in three out of the five MSUD patients who participated in the trial. The reduction in leucine, the most toxic of the BCAAs, in the three responsive MSUD patients ranged between 28-34%, which is considered by clinicians to be a meaningful response.

Investigators at BCM further explored the mechanistic rationale why NaPB lowered BCAA/BCKA levels. NaPB was found to be an allosteric inhibitor of the branched-chain keto acid dehydrogenase complex kinase (BCKD-kinase), and enzyme that regulates the activity of the branched-chain keto acid dehydrogenase complex (BCKDC) enzyme that is responsible for the normal metabolism of BCKAs.2 By inhibiting the BCKD-kinase, the BCKDC is constitutively activated, thus the increased activity results in a reduction in the plasma levels of BCAA and BCKA in all people, including those with MSUD,3 suggesting that NaPB may be an effective treatment for people with MSUD, who experience elevated BCAA levels.2,3

In November 2020, study results evaluating the effect of NaPB in the management of acute MSUD attacks in pediatric patients (n=10) were published in the Journal of Pediatric Endocrinology and Metabolism showing a significant reduction in leucine levels in MSUD patients experiencing an acute attack.4 The results suggested that NaPB can be safely administered in combination with emergency protocol and may provide additional clinical benefit beyond emergency protocol alone. However, verifying this outcome would require additional validation in a controlled trial. If ACER-001 is approved for the treatment of chronic MSUD, we believe patients will not be required to interrupt their therapy in the event of an acute crisis.

We anticipate initiation of clinical studies evaluating ACER-001 in MSUD to occur in late 2021, subject to additional capital. If these clinical studies are successful, we plan to seek FDA approval to market ACER-001 for the treatment of MSUD in the U.S. by submitting a 505(b)(2) NDA incorporating data from BUPHENYL’s® NDA (the reference listed drug) while supplementing our intended NDA for ACER-001 with additional PK, PD, efficacy and safety data specifically in the MSUD population, subject to our ability to generate sufficient capital resources to fund this program. We also intend to seek approval in the European Union and other territories outside the U.S. after the 505(b)(2) NDA for treatment of MSUD is filed. Additional information on the ACER-001 program can be found in our current corporate presentation.

ACER-001 is an investigational drug in the U.S. and is not currently FDA approved for MSUD.


  1. Scaglia F, et al: Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Mol Genet Metab. 2004;81(Suppl 1):S79-S85.
  2. Brunetti-Pierri N,et al. Phenylbutyrate therapy for maple syrup urine disease. Hum Mol Genet. 2010;19:631-640.
  3. Burrage LC, et al. Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders. Human Molecular Genetics 2014;23:R1-R8.
  4. Tanyel Zubarioglu, et al. “Impact of sodium phenylbutyrate treatment in acute management of maple syrup urine disease attacks: a single-center experience”