Emerging Startups Take Aim at Lysosomal Storage Disorders

March 10, 2022 - 4 minutes

Lysosomal storage disorders such as Niemann-Pick type C have proved difficult to tackle in the biotech industry. With recent funding rounds in the bag, Scenic Biotech and Maze Therapeutics strive to treat these conditions by activating protective genes.

Lysosomal storage disorders are inherited conditions caused by mutations in metabolic enzymes found inside our cells, leading to the buildup of toxic chemicals in tissues. Many of these rare and often lethal diseases lack effective treatments and European drug developers have hit major obstacles in the quest to deliver new medicines for these conditions. 

In 2020, for example, the French firm Lysogene was hit with a clinical hold from the FDA following safety concerns surrounding its gene therapy for the rare condition mucopolysaccharidosis type IIIA (MPS IIIA). A patient death in the same year further clouded Lysogene’s efforts. And earlier this year, Lysogene’s development partner Sarepta pulled out of their MPS IIIA collaboration, citing supply disagreements

The last year has also seen the FDA and EMA reject a small molecule drug developed by the Danish company Orphazyme for the treatment of a lysosomal storage disorder called Niemann-Pick type C (NPC). 

Nonetheless, there is an emerging movement that aims to turn the situation around for sufferers of lysosomal storage disorders. Maze Therapeutics in the US and Scenic Biotech in the Netherlands are examples of firms developing drugs that target genetic modifiers — genes that protect some people from disease. Maze Therapeutics raised €172M ($181M) in January this year, and Scenic Biotech raised a €28M Series A round this week.  

The space is hot,” said Oscar Izeboud, CEO of Scenic Biotech. “It appears that Maze and Scenic are frontrunners in the area of genetic modifiers.

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Maze’s strategy involves trawling scientific literature and population genetics data with artificial intelligence (AI) to find druggable genetic modifiers. The firm’s pipeline includes a phase I-stage treatment for the lysosomal storage disorder Pompe disease, in addition to preclinical-stage treatments for other indications such as amyotrophic lateral sclerosis and chronic kidney disease. 

Scenic, meanwhile, focuses its genetic modifier research on knocking out genes in cell cultures. The company is planning to enter a cancer treatment into phase I trials in 2023, and is working on preclinical programs in NPC and a rare mitochondrial disorder called Barth syndrome. Scenic is also working with Genentech to develop drugs for genetic diseases.

Scenic’s immuno-oncology drug blocks a protein that helps cancer cells evade the immune system in a similar way to blockbuster checkpoint inhibitor antibodies. Scenic’s drugs could be combined with current cancer treatments to enhance the effects of the therapies.

NPC, the most advanced indication in Scenic’s rare disease pipeline, lacks sufficient approved treatments. One of the few options in the EU is miglustat, a drug that prevents the harmful buildup of toxic chemicals that lead to symptoms of NPC. However, no current treatments can tackle the underlying cause of the disease.

There are numerous drug programs globally vying to better treat NPC; one of the most advanced was Orphazyme’s rejected candidate, which is currently in development limbo. Scenic aims to enter its own drug into clinical trials in 2024.

We found a new, specific, biological mechanism of action which is distinct and different from other attempts to target NPC,” said Izeboud. “We believe that because of this genetic modifier approach we may be onto something new and exciting that could allow us to succeed where other treatments have failed.” 

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Another front in the fight against lysosomal storage disorders is gene therapy, which could restore the function of metabolic enzymes long-term. Lysogene’s MPS IIIA candidate is leading the gene therapy pack in lysosomal storage disorders. Other European gene therapy hopefuls in the space include Esteve in Spain and the UK firm Freeline Therapeutics.

Scenic Biotech and Maze Therapeutics aim to push the boundaries of genetic modifier research in drug development, including lysosomal storage disorders. In the future, genetic modifiers could also become key targets for gene editing firms such as Editas Medicine and CRISPR Therapeutics.

Targeting genetic modifiers allows us to find potentially disease-modifying treatments,” concluded Izeboud. “This is a hugely promising area of research, still mostly uncharted territory, where exploration should allow us to find completely novel treatments.

Cover image via Elena Resko

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