Sanofi SA / Maze Therapeutics, Inc.

Pompe disease (late-onset; oral substrate reduction therapy)

5K US cases/yr · $1.2B Pompe franchise 2023 global sales (Myozyme/Lumizyme + Nexviazyme, Sanofi) · 750 Sanofi-Maze deal size (USD MM, $150M upfront + equity + up to ~$600M milestones) — subsequently terminated

Disease Overview

Pompe disease (glycogen storage disease type II, acid maltase deficiency) is an ultra-rare autosomal recessive lysosomal storage disorder caused by deficiency of acid alpha-glucosidase (GAA), leading to lysosomal glycogen accumulation in skeletal, cardiac and respiratory muscle. US prevalence is estimated at approximately 3,500 to 5,000 patients across infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD) (NORD / Sanofi Pompe registry). IOPD presents in infancy with hypertrophic cardiomyopathy and progressive weakness; untreated survival beyond 12 months is rare. LOPD, the dominant commercial population, progresses over years to decades with limb-girdle weakness, respiratory insufficiency and loss of ambulation. Standard of care since 2006 has been enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme / Lumizyme, Sanofi), followed by next-generation avalglucosidase alfa (Nexviazyme / Nexviadyme, Sanofi, approved 2021) and the Amicus Therapeutics combination cipaglucosidase alfa + miglustat (Pombiliti + Opfolda, FDA approved September 2023). Pompe combined 2023 sales across Sanofi's franchise were approximately $1.2B (Sanofi FY2023). Maze Therapeutics' MZE001 is an oral, small-molecule glycogen synthase 1 (GYS1) inhibitor designed as a substrate reduction therapy (SRT), adjunctive or potentially alternative to biweekly IV ERT — an attractive profile given the ERT administration burden.

Competitive Landscape

The Pompe disease landscape is dominated by Sanofi ERT assets with Amicus emerging as the sole approved competitor and several pipeline programs attempting to redefine the modality mix. Approved ERTs: alglucosidase alfa (Myozyme US IOPD / Lumizyme US LOPD, Sanofi) — first-in-class, biweekly IV, approved 2006; avalglucosidase alfa (Nexviazyme US / Nexviadyme EU, Sanofi) — next-generation ERT approved 2021 with improved M6P receptor targeting. Approved combination: cipaglucosidase alfa + miglustat (Pombiliti + Opfolda, Amicus Therapeutics) — FDA approved September 2023, EU approved March 2023, adult LOPD. Pipeline — oral substrate reduction therapy: MZE001 (Maze Therapeutics) — oral GYS1 inhibitor, Phase 1 data at deal announcement, novel mechanism. Pipeline — gene therapy: SPK-3006 (Spark / Roche, suspended); AT845 (Astellas, Phase 1/2 on partial hold 2022 due to peripheral neuropathy SAE); RGX-121 (REGENXBIO, distinct lysosomal disorder). Second-generation ERT: ATB200-AT2221 combination (Amicus, same program). Maze's platform thesis was that oral SRT could complement or eventually supplant ERT for ambulatory adults; Sanofi's December 2023 termination followed FTC action blocking the transaction on antitrust grounds, reflecting Sanofi's dominant Pompe position.