The Mitochondria are the powerhouses of every cell. This is something that we all learned a long time ago in 8th grade biology. However, the story of the role of the mitochondria goes much deeper than just providing power. We know now that the mitochondria may be the cause of a legion of diseases when it malfunctions and restoring the tiny organelle’s behavior with targeted specific drug therapies, may provide truly meaningful new tools for physicians for treating their patients with neurodegenerative diseases and giving hope.
Beyond making energy for our cells to function (ATP), mitochondria also play a huge role in storing calcium used in cell signaling and produces free radicals in normal functioning cells. When gone wrong, mitochondria can be overloaded with calcium that can kill the cell by changing osmotic pressure, while producing free radicals that can damage DNA, proteins, and lipids, that collectively accelerate aging and tips the scales towards disease onset.
Mitochondria are found in all cells throughout the body except mature red blood cells and are especially important in energy demanding cells with low capacity for removing free radicals such as the neurons in the brain. This makes these cells particularly vulnerable if the mitochondria start to misbehave.
Luckily, a new drug platform is emerging that penetrates the brain and changes the entire mitochondrial physiology towards pro-survival and may be useful for treating a broad range of diseases beyond neurodegenerative, such as neuromuscular, autoimmune, developmental and trauma such as severe concussions that can cause cognition and hearing loss.
Working towards this goal is Mitochon Pharmaceuticals, Inc., a clinical stage biotech company, with an open IND in Phase-I human safety testing. The company is headed by a group of industry veterans, with drug discovery, broad scientific, clinical, and managerial experience, including taking a drug through FDA approval, M&A, and multiple financing rounds.
Mitochon is focused on developing MP-101 and MP-201, “disease-modifying” drugs that specifically target the mitochondria and attenuate neurodegeneration, with a focus on the diseases of Huntington’s & ALS (both with FDA awarded Orphan designations), progressive supranuclear palsy (PSP), multiple sclerosis (MS), Alzheimer’s and Parkinson’s.
Not to be missed, their prior work on Traumatic Brain Injury (TBI), was recently rewarded with a $3.2 million NIH/NINDS grant for further development at the Children’s Hospital of Philadelphia (CHOP) and University of Kentucky.
“Our programs to date have been shown to protect cells by modulating the mitochondria to reduce oxidative stress, improve calcium handling, and promote repair through mitochondrial biogenesis and production of neurotrophins (BDNF),” shares team Mitochon. Together these effects create stronger, healthier, and more resilient mitochondria, which then improves the symbiotic relationship in the cell and natural compensatory mechanisms resist further disease progression with a possibility of some repair.
Mitochon has focused its research efforts on understanding the mitochondria and the role it plays in neurodegenerative diseases. What makes it unique in this aspect, is that its compounds modulate the entire mitochondrial physiology and not simply one aspect of it – thus the power of the company’s approach lies in bolstering cellular resilience and modifying disease progression.
“Our approach is to strengthen mitochondrial health and prevent degenerative processes from advancing thus slowing down or halting disease progression with a simple oral, once-per-day brain penetrating drug that wakes up compensatory mechanisms towards survival and repair. This approach, we believe makes us a preferred choice in the neurodegenerative space,” says the team.
Driven with Excellence
As described earlier, the company’s primary focus is on treating neurodegenerative diseases like ALS, Huntington’s, Alzheimer’s, Parkinson’s, PSP, and MS. These conditions have no or few “disease modifying” treatments, leading to severe morbidity and early death.
The mitochondria are unique among all the organelles within the cell for being the only organelle with a pH basic environment. The unique mild pH acidic chemistry of Mitochon’s drugs draws them to the inside of the mitochondria called the matrix, where the molecule releases a proton, hydrogen. This event changes everything. Free radicals stop being overtly produce, calcium overload is reduced and even the mitochondria itself can be pushed to make newer healthier ones giving the cell a chance for survival with a better “population” of mitochondria. So, this stops the damage, but then it cascades into inducing factors involved in repair, learning and cognition. The mitochondria from all mammals are very well evolutionarily conserved in function and the drug’s mechanism of action (MOA) is based on physics. Both give this unique platform a leg up on other drugs for excellent translation from mouse to human. In addition, since the drugs specifically target the mitochondria, reducing, “off-target” side-effects providing a leg up too in safety.
Collectively, Mitochon’s oral bioavailable brain penetrating drugs stimulate the formation of new mitochondria through biogenesis (mitophagy), induce secondary messenger cAMP and neurotrophins in the brain that are critical to support neuronal growth and nourishment. This makes the drugs suitable to treat multiple diseases.
Introducing the personalities who are involved centrally with the direct success of Mitochon Pharmaceuticals is certainly a genuine pleasure. Robert Alonso the Founder and CEO of the company has 25 years of extensive experience in both large pharmaceutical companies (Merck, Roche) and small biotech companies (Ceptaris).
Most recently, Alonso successfully founded Ceptaris Therapeutics, where he raised over $40 million in venture capital, steering the lead program through phase III testing, and filing of an NDA (Approval was received in 2013). Mr. Alonso is a seasoned executive who has completed numerous licensing and other business transactions, including raising venture capital.
Another prominent name in the panel is Dr. John G. Geisler, PhD, Founder and Chief Scientific Officer of Mitochon. With more than 25 years of rich experience in drug discovery research and role in the inception of new ideas, with consistent focus of work has been towards analyzing and solving the root of the problems has led to development of this platform and Mitochon. He has contributed 15 years of his life on metabolic drug discovery for Pfizer, Ionis, and JnJ. He has expertise in mitochondrial energy expenditure from years of attempting to partition lipids in restoring insulin sensitivity and reducing the comorbidities associated with the ‘over-nutritional phenotype’.
One of the associates of the duo mentioned above is Dr. Marcus Keep, MD, a neurotrauma neurosurgeon and Acting Chief Medical Officer of the company. Dr. Keep is clinician, scientist and has 20 years of entrepreneurial experience in biopharmaceutical activities. He has been involved in many aspects of basic and translational research, writing patents, orphan drug designation, IND application, grant acquisition, and fundraising. He is a diplomat of the American Board of Neurological Surgery and a Fellow of the Royal College of Surgeons of Canada. With such a robust line-up of leadership, Mitochon has what it needs to bring its drugs to clinical and marketing approval, to benefit patients and shareholders.
We asked the team at Mitochon about their opinion on the future of the pharma industry, to which they said, “The pharmaceutical industry will emerge stronger than ever post Covid-19. Vaccines, medications that save lives and the continued threat of new pathogens has reinforced to the public, the great value that the pharmaceutical industry brings to the world. It is a wonderful time for the medicine and pharmaceuticals sector. We truly hope to be at the forefront of this new era. We are quite optimistic that areas such as neuroscience that have had difficult time with funding in the past will be helped by the rapid advances that have occurred during the Covid-19 era. We are ready to scale quickly and look forward to taking our compounds into clinical studies for Huntington’s disease and ALS – helping the many people with these devastating diseases,” expresses the Mitochon team.
The duo, sharing their advice to the budding entrepreneurs and enthusiasts aspiring to venture into the pharma sector, say, “We believe this is a great time for venture creation and pharmaceutical/biotech development. Mitochon was created by thinking outside the box and pushing past old dogmas to bring forward new ideas, new approaches in a space that has a history of clinical failures. We encourage all budding entrepreneurs and scientists to take the leap with great ideas and align with like-minded motivated people. This, along with capital, are the pillars to success and now is definitely a good time to be developing treatments that will have a profound effect on our world and our future.”
Dynamics of Mitochon
Mitochon Pharmaceuticals will measure mitochondrial function in treated patients to determine whether their drugs have just as profound an impact on human mitochondrial health, similar to the powerful observations made in research animals.
“The COVID-19 crisis only had a temporary impact delaying our clinical trial work, but now we are full speed ahead,” says Mr. Alonso. Patients recently resumed entry into clinical trials, with safe social distancing. The academic institutions that were also initially closed, have restarted their Mitochon research. “As a company we are still quite small and operate remotely in a virtual way, which is quite efficient with time – so social distancing has never been a problem for us,” assures Dr. Geisler.
Dr. Keep thinks that as a developing biotech company, they were fortunate that their original discoveries bloomed beyond what was initially imagined. The pharmacology of their two drugs, MP-101 and MP-201, turned out to have very broad neuroprotective effects, with numerous possible indications where people could be helped.
“We tested these compounds in 10 truly diverse neurological indications, with statistically positive neuroprotective findings. We chose to focus first in humans on the worst truly insidious afflictions like ALS and Huntington’s disease, for which we have Orphan designations. We plan multi-indication Phase-2 clinical studies of these worst diseases in 2021. Potential trials in other devastating brain conditions include Alzheimer’s, Parkinson’s, PSP and MS,” he adds.
The diseases Dr. Keep mentioned are all associated with mitochondrial dysfunction, which the company aims to restore with its drug therapies. Mitochon in the future would like to launch their drugs in the market thereby helping the patients with deteriorating brains who today have very few options. “Keeping people home, able to talk, move, and remember, being self-sufficient for as long as possible, is our main long-term goal,” describes the team of Mitochon.
Financially, the company wishes to facilitate optimum ROI to its investors via an IPO, M&A, or license. “We are patient focused first. If we are successful for our patients, we know return for investors will follow naturally,” the bioentrepreneur trio concludes.