MitoRx Therapeutics’ CEO on how the small biotech already has several drug candidates for age-related diseases that target mitochondrial dysfunction.
Last week, MitoRx Therapeutics announced itself to the world, securing seed funding for its work to develop mitochondrial-protective therapeutics designed to halt the progression of degenerative diseases. Licensing the IP developed by University of Exeter Professor Matt Whiteman, the company has secured access to a pipeline of compounds with therapeutic potential against age-related disease.
Interestingly, some of the compounds being developed by MitoRx are part of the wonderfully named “Space Worms” project currently underway on the International Space Station, which aims to determine the causes of muscle changes during spaceflight and find ways to mitigate them.
Longevity.Technology: Many early-stage longevity ventures would be more than happy to have identified a single compound with therapeutic potential, but MitoRx is drinking from the proverbial fire hose. The startup has access to a library of small molecules identified for indications including [deep breath] Duchenne muscular dystrophy (DMD), CBS-deficiency and Huntington’s disease, expandable to Alzheimer’s, Parkinson’s, sarcopenia, cancer cachexia, COPD and IPF! We caught up with Dr Jon Rees, CEO of MitoRx to learn more.
After meeting Professor Whiteman at a conference four years ago, Rees became increasingly interested in the professor’s work in mitochondrial-targeted sulfide donor technology.
“Some 20 years ago, Matt synthesised the first non-targeted slow-release sulfide donor and went on to invent the first mitochondrial-targeted slow release sulfide donor and in doing so founded the field,” he says. “I became more and more curious and enthralled in the hypothesis, and I was so impressed by the potential of the platform technology that I asked to spin the company out of the university – essentially to evaluate and in-license the IP developed by Matt.”
Multiple age-related disease indications
Trans-sulfuration dysfunction is linked to mitochondrial dysfunction and many age-related diseases. The technology being in-licensed by MitoRx exploits an endogenous mechanism which mediates sulfide-signalling and ultimately reverses mitochondrial dysfunction.
But what really excited Rees was the fact that Whiteman had conducted a vast amount of work across a wide range of specific age-related disease models.
“Matt collaborated with people all over the world, conducting joint research to verify the pharmacological activity of his original tool compounds in multiple disease models,” he says.
“When I first met him, Matt reeled off a series of disease models in which his tool compounds had activity, which was extremely impressive because you’re used to meeting people who say that they’re about to test something in a disease model. But here we had multiple independent confirmations – over 20 in vivo papers and additional in vitro papers – confirming pharmacologic activity.”
Paper highlights include the complete reversal of loss-of strength due to mitochondrial dysfunction in a C. elegans model of Duchenne muscular dystrophy (DMD), as well as neuroprotection against Alzheimer’s disease in mice, through the restoration of sulfide-signalling.
First company in the field
Rees is keen to point out that last year was the 25th anniversary of the discovery of the sulfide-signalling field by Professor Hideo Kimura of Japan’s Sanyo-Onoda City University, who has welcomed the emergence of MitoRx.
“For all those years, there have been no biotechs developing drugs to restore sulfide signalling, until now,” says Rees. “We are the world’s first biotech company seeking to restore the treatment of diseases involving sulfide signalling, which also happen to be diseases of aging, or appear as accelerated aging. They have lots of the same features that you see in aging, including muscle disease and brain disease – neurodegeneration or impairments in cognition.”
Rees says that MitoRx was formed in early 2021, and subsequently “in-licensed everything there was to be in-licensed” relating to Whiteman’s work in this area. The cornucopia of novel compounds present in the lab’s freezers was quite astonishing, spanning four or five different chemical classes, and the first task for MitoRx was to go through them all to identify and subsequently file patents on them.
The company is initially focusing on a few specific indications, including Duchenne muscular dystrophy (DMD), CBS-deficiency, and Huntington’s disease.
“They are pragmatic choices, where the biology fits, where the evidence is strong,” says Rees. “Faced with the riches of potential opportunity and what is potentially a broad platform, our approach is to balance where the biology fits with unmet medical need. There is strong evidence that the mitochondrial dysfunction that we can reverse is present within DMD. And there is a growing recognition of the importance of mitochondrial dysfunction in driving neuromuscular disease, rather than resulting from it.”
Success will lead to more age-related disease indications
Should MitoRx prove to be successful in those initial indications, Rees is confident of success in additional diseases.
“In practice, if we are lucky enough to be fulfilled in our ambitions to arrest decline in muscular dystrophy, we would expect to arrest sarcopenia in aging, and in cancer cachexia. If we’re successful in Huntington’s I expect to be successful in specific subsets of Parkinson’s and Alzheimer’s patients. So, the potential of the platform is vast.”
It’s important to note that, while hydrogen sulfide is recognised as an industrial toxin, MitoRx believes it has found a way to use it safely.
“We don’t want to put sulfide in any quantity anywhere else but where it’s needed, so the substances that we’ve created are extremely potent, and only need to be used in very small quantities to achieve a significant effect,” says Rees. “For example, the relative potency of one of our tool compounds is four million times the potency of a steroid in a dystrophic model of movement restoration. This is a regulatory effect that we’re having – we’re modulating mitochondrial metabolism.”
Having secured seed funding, MitoRx is now focused on some “critical translational mouse models” to generate in vivo proof of concept, which should then allow the company to secure the next round of funding to take one or more of its compounds into Phase 1 clinical trials.
