What if you could treat a genetic disease without actually fixing the defective gene?
That's the fascinating idea behind a new approach being developed for devastating pediatric lysosomal storage disorders. These diseases can have completely different genetic causes - but ultimately disrupt some of the same cellular machinery.
So instead of trying to correct every individual mutation, could we enhance the cell's own ability to recycle and clear the material that is accumulating inside it?
Today we're going inside the lysosome - the cell's recycling center - with Alex Yang, CEO of Polaryx Therapeutics ( https://polaryx.com/ ), to explore whether repairing the cell's downstream machinery could change the course of rare neurodegenerative diseases.
Today we're going to explore one of the most challenging areas in medicine - developing treatments for rare, devastating diseases that often begin in childhood, progress rapidly, and can have extraordinarily limited treatment options.
My guest is Alex Yang, J.D., LL.M., Chairman and CEO of Polaryx Therapeutics, a clinical-stage biotechnology company developing disease-modifying therapies for rare pediatric lysosomal storage disorders.
Lysosomal storage disorders are a family of more than 70 inherited diseases in which mutations disrupt the cell's lysosomes - essentially the cell's recycling and waste-processing machinery. As undegraded material accumulates, cells become dysfunctional, inflammation develops, and in many of these diseases neurons progressively die.
Polaryx's lead program is PLX-200, an oral formulation of the repurposed drug gemfibrozil that is being investigated for its ability to activate PPARα and increase expression of TFEB - a master regulator of lysosomal biogenesis and autophagy. The idea is fascinating: rather than trying to correct each individual genetic defect, could we enhance the cell's own machinery for clearing the toxic material that accumulates downstream of many different mutations?
Polaryx is preparing to launch SOTERIA, an IND-authorized Phase 2 basket trial designed to evaluate PLX-200 across four pediatric lysosomal disorders - CLN2 and CLN3, forms of neuronal ceroid lipofuscinosis or Batten disease, as well as Krabbe disease and Sandhoff disease. The company is currently targeting initiation in the fourth quarter of 2026.
And Alex brings a particularly interesting perspective to this story. He is not a traditional career scientist. He trained as an attorney, earning both a J.D. and LL.M. from NYU School of Law, and previously worked across investment banking, international tax, consulting and private equity. Over the past decade, through Mstone Partners ( https://www.mstonepartners.com/ ), he has also built and led healthcare and biotechnology companies, overseeing everything from preclinical development and clinical operations to licensing, M&A and public-market transactions.
In fact, one of the companies he previously led, pediatric epilepsy biotech Epygenix Therapeutics, was acquired by Harmony Biosciences in 2024 in a transaction valued at approximately $680 million.
So today we're going to look at both sides of the equation: the biology of lysosomal storage disorders and the science behind PLX-200 - but also what it takes to turn an idea into a clinical-stage therapy for children with diseases where every year can matter enormously.
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