Autobahn Therapeutics Presents Preclinical, Proof of Concept Data for ABX-002 for the Treatment of Adrenomyeloneuropathy

Autobahn Therapeutics, a biotechnology company focused on restoring hope for people affected by CNS disorders, today announced the presentation of preclinical data of ABX-002, a CNS-penetrating prodrug that provides a balanced delivery of LL-340001, a potent and selective thyroid hormone receptor beta (TR?) agonist, for the potential treatment of adrenomyeloneuropathy (AMN), a progressive and debilitating rare disease. The data will be highlighted in a poster presentation at the American Academy of Neurology Annual Meeting, which is being held virtually from April 17-22, 2021. Posters will be made available at the start of the conference and remain viewable online through the virtual forum for 30 days after the meeting.

In the research presented, Autobahn evaluated ABX-002, a fatty-acid amide hydrolase (FAAH)-mediated prodrug delivering an active TR? agonist, LL-340001, in preclinical models of AMN. Findings showed:

• ABX-002 led to dose-dependent increases of multiple thyroid hormone-regulated genes in vitro;
• ABX-002 resulted in approximately 30-fold increased potency in the CNS, compared with LL-340001 alone in vivo; and
• ABX-002 dosed orally at either 30 or 100 µg/kg for 12 weeks increased thyroid hormone target genes including ABCD2 expression and decreased very long chain fatty acids (VLCFAs) in brain tissue and plasma in an Abcd ^-/y mouse model.

"We are very excited to share these data with ABX-002, which support Autobahn's approach of leveraging our brain-targeting chemistry to create potent and selective therapeutics for the treatment of CNS disorders, like AMN," said Brian Stearns, Ph.D., chief scientific officer of Autobahn. "AMN is a highly debilitating disease, leading to motor disabilities, fatigue, ataxia, sensory loss, adrenal insufficiency, incontinence and impotence, with no currently approved treatments. These data show that administration of ABX-002 resulted in potent and on-target responses in preclinical models of AMN and support our continued advancement of ABX-002 toward clinical evaluation for the treatment of people with this rare and very difficult disease."

AMN is characterized by a toxic buildup of VLCFAs in the CNS and periphery, accompanied by demyelination. This buildup is driven by mutations in the ABCD1 gene which encodes a transporter that shuttles cytosolic VLCFAs into peroxisomes for degradation.

"A potential therapy that can address the toxic buildup of VLCFAs in AMN patients would be of great value," said Florian Eichler, director of the Leukodystrophy Service at the Massachusetts General Hospital, and a medical advisor to Autobahn.

ABX-002 acts by increasing expression of ABCD2, a compensatory transporter which functionally compliments defective ABCD1 and is a direct target gene of thyroid hormone. By increasing thyroid hormone signaling, ABCD2 expression is increased, leading to a reduction of VLCFAs. ABX-002 also stimulates remyelination by promoting the differentiation of oligodendrocyte precursor cells, which may be of additional benefit to AMN patients.

About Autobahn Therapeutics

Autobahn Therapeutics is focused on restoring hope for people affected by CNS disorders. Autobahn is leveraging its brain-targeting chemistry platform to unlock new therapeutic opportunities through precision tuning of the central exposure of its molecules. The company's pipeline is led by ABX-002, a thyroid hormone receptor beta agonist for the treatment of adrenomyeloneuropathy (AMN), a rare genetic disorder. Autobahn Therapeutics is based in San Diego. For more information, visit www.autobahntx.com.