Special delivery: MitoRx Therapeutics builds out expertise to accelerate development of mitochondrial-protective therapeutics.

MitoRx Therapeutics, a biotech developing therapeutics that reverse mitochondrial dysfunction, thereby arresting the progression of degenerative diseases, has announced a raft of appointments that are set to accelerate the company’s novel pipeline through the closing of its Advanced Subscription and beyond.

The company welcomes Christine Charman as Chief Development Officer and David Richardson as Finance Director.

And, in addition, MitoRx has made four appointments to its Scientific Advisory Board (SAB): Professor Chas Bountra, Professor Dame Kay Davies, Professor Laurent Servais, and Dr Bernd C Schwahn.

Longevity.Technology: There are three weeks left for subscribers to make commitments to invest in MitoRx’s Advanced Subscription Agreement (ASA). The company told us that substantial ASA commitments have been made and are already at bank, with MitoRx having entered term sheet negotiations at a significantly higher pre-money than the ASA.

It is not surprising that interest in the Oxford- and Exeter-based biotech is hotting up, especially since the company’s compounds have been shown to supress fibrosis in a murine COPD model, reducing loss of function and immune cell infiltration [1].

In addition, MitoRx has demonstrated the first complete restoration of movement in a dys-1 model of Duchenne muscular dystrophy (DMD), a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of dystrophin, a protein that helps keep muscle cells intact; MitoRx has garnered evidence its approach does modulate muscle sulfide in a certain mouse model of DMD.

The sulfide-signalling impairment in DMD is also present and progressive in aging as measured by protein persulfidation levels, meaning that muscle wasting in aging – sarcopenia – is directly relevant to MitoRx’s technology. In fact, evidence is starting to come to light that shows crude hydrogen sulfide donors reduce muscle atrophy – although the compounds used in academic research are unsuitable for development as pharmaceuticals. Instead, MitoRx has been developing and manufacturing the first safe drug-like sulfide donors, and can now address such challenges with potential clinical candidates; the company is closing the gap between the theory and clinical potential.

Mitochondrial bioenergetics is proving to be an interesting space, and we reached out to Jonathan Rees PhD, CEO of MitoRx, for his take on the company’s journey through it.

Rees told Longevity.Technology: “The key mitochondrial metabolic transactivator is regulated by sulfide-signalling, so it is no surprise that in conditions where hydrogen sulfide generation is impaired, applying our compounds restores mitochondrial bioenergetics as measured by the generation of ATP.

“I’m hoping MitoRx becomes the posterchild of longevity as an example of the new breed of longevity biotech which delivers on the promise, rather than being on an un-ending journey. Now having two team members who have taken four products to market and a world-class SAB means we have a stronger than ever team on which to deliver rather than promise.”

Adding that the team’s confidence is underlined by a cash commitment of over £200,000 which has been made alongside the company’s investors since inception, he said: “I am delighted that we’ve been able to add such a depth of expertise, knowledge and capability to our team, joining us in our fight against diseases of ageing, and degenerative diseases which have been likened to accelerated ageing.”

In addition, Norman Law PhD, Co-Founder and Director of MitoRx told us: “MitoRx is unique among 21st century biotechs because we have developed novel potential medicines that return tissue levels of hydrogen sulfide in disease to that of wild-type, with one-million-fold greater potency than the compounds used in academia. Our ‘secret sauce’ means we can achieve the desired restoration-of-sulfide-signalling effect without any of the undesirable toxicity of hydrogen sulfide for which we have a cultural fear, as a results of industrial spills in the 20th century.”

Under starters’ orders…

Professor Chas Bountra OBE is now Chair of the Scientific Advisory Board. He commented on his appointment: “It’s an honour and a pleasure to come together with top international scientific and clinical experts to build the MitoRx Scientific Advisory Board. Together we are working to become a global leader in treating diseases caused by impaired mitochondrial function.”

Bountra is Pro-Vice Chancellor for Innovation at the University of Oxford, Professor of Translational Medicine in the Nuffield Department of Clinical Medicine, Director of the Centre for Medicines Discovery, and Professorial Fellow at Keble College, Oxford. Prior to coming back to Oxford in 2008, he was Vice President and Head of Biology at GlaxoSmithKline. An invited expert on several government and charitable research funding bodies, Bountra is an advisor for many academic, biotech and pharma drug discovery programs. In 2012 he was voted one of the “top innovators in the industry”, in 2014 received the “Rita and John Cornforth Award” from the Royal Society of Chemistry, in 2017 and 2018 was voted Master of the Bench from the Medicine Maker Power List, and in 2018 was awarded the Order of the British Empire in the New Year’s Honours List.

Also joining the board is Professor Dame Kay Davies CBE DBE FRS FMedSci, Dr Lee’s Professor of Anatomy Emeritus at the University of Oxford with an international reputation for work on Duchenne muscular dystrophy paving the way for several nucleic acid related therapies. Davies is a co-founder and co-Director of the MDUK Oxford Neuromuscular Centre, and she co-founded Summit Therapeutics plc to translate her work into the clinic.

Professor Laurent Servais MD PhD directs the Specialised Translational Research Oxford Neuromuscular Group as Professor of Paediatric Neuromuscular Disease at the University of Oxford, and he is Professor of Child Neurology at the University of Liège. He brings a wealth of experience to the Scientific Advisory Board having led many clinical trials as principal investigator for Duchenne muscular dystrophy and spinal muscular atrophy treatments.

Dr Bernd C Schwahn MD PhD FRCPCH, Consultant in Paediatric Metabolic Medicine at the Manchester University NHS Foundation Trust and Honorary Clinical Senior Lecturer in Genomic Medicine, also joins the board. Schwahn’s scientific interest focuses on disorders of sulfur amino acid metabolism and has been involved as principal and chief investigator in clinical trials for the treatment of molybdenum cofactor deficiency, lysosomal storage disorders and disorders of intermediary metabolism.

Chief Development Officer Christine Charman PhD comes with close to 26 years’ experience in accelerating transformational therapies as Senior Global Program Lead for Takeda’s Rare Diseases, Respiratory and Immunology and Neuroscience therapy areas. She also worked as consultant CDO at Izana Bioscience and development consultant for a range of Biotechs and NewCos and Program Lead supporting UK Vaccine and Antiviral Task Forces, with further development experience at Novartis from preclinical research leadership to Senior Global Programme Director, including the planning, clinical execution and launch of two products.

David Richardson BSc ACMA AMCT brings over 30 years’ finance experience to his new role as Finance Director. He has held board positions at a number of venture-backed technology companies and his experience in the industry includes senior finance roles within both AstraZeneca and Evotec.

CEO of MitoRx, Jonathan Rees PhD, commented: “We are thrilled to welcome our new SAB members, as well as Christine Charman as Chief Development Officer and David Richardson as Finance Director, who together bring a wealth of renowned experience across financial, scientific and clinical backgrounds.

“The wide ranging expertise gained from our growing team and advisory board will accelerate progress of our first-in-class, first-in-target small molecules which are now being pre-clinically tested in a mammalian model of muscular dystrophy. We look forward to working with them all.”

[1] https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A2413