Mitochon Pharmaceuticals was launched in November 2014 with joint seed money from Ben Franklin Technology Partners and private investors. Mitochon was founded by Robert Alonso, MBA, and John Geisler, Ph.D., with the goal of creating disease modifying treatments for a variety of neurological conditions with unmet medical needs, such as ALS, Huntington’s disease, and traumatic brain injury (TBI). The thesis ofMitochon’s approach is that if you bolster mitochondrial health through a mechanism known as mitochondrial uncoupling, meaningful pro-survival benefits occur and brain cells are protected from damaging disease processes.
Dr. Geisler’s post-doctoral work at Pfizer and Yale University in metabolic disease, taught him that there are master switches (proteins to target with medicines) that can have a profound effect on disease progression. This knowledge became the theme of his subsequent work in drug discovery working at the roots of problems. By removing fat from the liver and muscle cells that cause insulin resistance, the aim was to wean individuals off the insulin and cure their diabetes.
Under the leadership of John G. Geisler, Chief Scientific Officer and Co-founder, Mitochon is working on developing two drugs, MP101 for rare diseases (orphan indications) and MP201 for larger markets such as Alzheimer’s, Parkinson’s, TBI, etc. MPlOl has ongoing clinical studies now, whereas MP201 is just starting the GLP toxicology studies to work towards an FDA-approved open IND.
Below are highlights of the interview that give insights about Mitochon Pharmaceuticals’ work resolving major health complications with the help of modern technological advancements.
What are the core values that Mitochon Pharmaceuticals stands by? What is its mission and vision statement?
Coming from working at a number of pharmaceutical companies, I think that there are two major themes we established at Mitochon.
- We have “no silos” in that we go after any indication (neuro, cancer, pulmonary, pain, ataxia, muscular dystrophies, trauma, etc.) as long as it is rooted in mitochondrial dysfunction and truly an insidious (time sensitive) diseases.
- We are not worried about how big the market is for the indication we are pursuing; rather, we want to fill a need for doctors to help their patients. For instance, my expertise is diabetes and obesity, but we have not pursued these indications as there are a lot of medicines to treat these diseases, but there is a great need in neurodegeneration in areas such as ALS, Huntington’s disease, MS, TBI, Parkinson’s disease, Alzheimer’s disease, etc. We are keenly interested in this area because our platform appears to be pan-neuroprotective by modulating the entire mitochondrial physiology of this organelle, which is central to the health of all cells.
How is your company incorporating advancing technology in providing the Concussion and TBI treatment to further customer reach as well as chart its growth upwards?
Mitochon’s concerns with TBI is that “today’s concussion patient often becomes tomorrow’s dementia patient.” It may appear bleak, but there is a real link with aging, and a need for an early- immediate treatment that is brain penetrant and quiets down the mitochondria post-trauma. After trauma, the cells are under enormous stress that sets up programmed cell death through the mitochondria, which requires immediate attention, not only from the area of direct impact but also from the neighboring cells under attack that I call the “threatened tissue.” There is also a need for those who don’t get treatment but are now older and need a treatment to push-off dementia. One of our first studies was in a model of Alzheimer’s Disease (AD) with 4 months of treatment with Mp101.
This proof-of-concept study was critically important because it showed that this oral once-per-day treatment enhanced cognition, as the AD mice learned faster to find the hidden platform in the Morris Water Maze, and when the platform was removed for the final exam, they became obsessed for three days with where it used to be. Loss of short-term memory is the hallmark of AD and arrows are pointing at the mitochondrial dysfunction as an early up-stream event triggering progression. Therefore, resolving this dysfunction with our mitochondrial specific drugs, MP101 or MP201, they may curb subsequent memory loss and perhaps even enhance cognition!
Because of this combination of the work in AD and TBI, it has helped secure joint funding from the BrightFocus Foundation, specialized in AD research and Medical Technology Enterprise Consortium (MTEC), military focused, to look closer at an issue particular to the military population that largely goes unnoticed by the civilian population, namely the damage caused by repetitive blast wave trauma.
When a soldier throws a hand grenade, breaches a wall, or pulls the trigger on a howitzer, there is a shock wave of air that penetrates the organs, spinal fluid up to the brain, the ears, eyes, and lungs, and rattles the whole brain, causing initially mild damage, but more penetrating and lasting issues with repetition. However, we also have TBI work in what we call “classical” TBI, which looks more like a car crash or clunk on the head. Acute head injury is associated with very high mitochondrial-derived free radical production that damages proteins, lipids and chromosomes and toxicity due to calcium overload that causes cell death (apoptosis).
Mitochon’s objectives are to complete GLP toxicology studies with our second drug, MP201, with enhanced pharmacology and to begin clinical studies for TBI at trauma units in all major cities across the United States. We will also seek approval to conduct clinical studies on military patients who have experienced repetitive blast wave trauma. This can significantly impact the field for optimal outcome measures during an unfortunate event by providing soldiers an immediate delivery of an injectable MP201 formulation in remote locations, while buying time to get transported to a clinical unit.
What are the key products and services of the company, and how is it impacting the demographic concerned?
Mitochon is in Phase I clinical studies now in the USA with MP101 and gearing up for a Phase I/Ila “basket study” in Europe scheduled for the summer of 2023 in three different indications: ALS, MS, and Huntington’s disease, but uniquely all treated with MPlOl as one indication. Most, if not all, neurodegenerative diseases have a central issue that is rooted in mitochondrial dysfunction, and MP101 appears to resolve this problem. In fact, not only neurodegenerative diseases, but we are finding that many diseases (cancer, heart, pulmonary, intestinal, etc.), in general, appear to have mitochondrial dysfunction.
What, according to you, are the challenges faced in supplying specialized services in the industry you are serving? How is the company, with your able guidance, turning them into opportunities?
Mitochondria are in all cells, and there are thousands per cell. As you age, the population moves from being homogenous to being heterogenous, or, as we like to say, mosaic. Some mitochondria produce a lot of energy (ATP) and low amounts of free radicals that can damage DNA, proteins, and lipids. In contrast, other mitochondria produce low amounts of ATP, but are high producers of damaging free radicals. Our drugs are unique in shifting the mitochondrial population from mosaic to homogenous.
Since the health of the mitochondrial “population” is critical for the health of the cell in this symbiotic relationship, our platform appears to be beneficial for a host of diseases.
As an experienced leader, what advice would you like to give to aspiring entrepreneurs and enthusiasts who wish to venture into the competitive industry that you are serving?
Young scientists will accumulate knowledge from reading literature, hands-on experiments that are successful and fail, and from colleagues, mentors, and conferences. These acquired experiences then propel you toward the formation of new, original ideas of your own. You have to know when your ideas have merit, even though others may tell you they do not. Papers from high impact-factor journals and “thought leaders” can be complete rubbish, establishing scientifically untrue dogmas that move the direction of research for 10-20 years in the wrong direction. So it becomes tricky to get off that track and back onto the direction of science again.
Working in big pharma taught me that there are a lot of decisions made on the direction of research that have nothing to do with science. If leadership is selling you on what can and cannot be done, determine if it is rooted in science or other things like risk adversity, politics, a lack of sophistication, knowledge or all of the above. If you are in “discovery”, the inception of new ideas, it is critical that the tone of the team’s brainstorming sessions be inviting for everyone in the room to share ideas, especially for the brilliant, but more reserved minds. There is a great benefit to initially working for big companies. So, go to big companies to learn about the industry, but know when it is time to leave if you are pushed to bury your ideas or work on incremental projects. You don’t want all of your time absorbed with nothing to show, and we need really fresh minds working on the hard stuff that are inspired. Question everything, read a lot, mull over ideas often, and stay on track to enable your ideas!
What are the future goals of your company and how has it envisioned to scale its operations and reach in 2023 and beyond?
Our immediate goals are to complete Phase I in humans and get into all the proof-of-concept studies in patients with a host of diseases to open the box completely. We need to complete the MP101 long toxicology package to get into critical long-term chronic studies for patients with ALS, Huntington’s, etc. These are all very expensive studies, so we are looking for investors to help us accelerate these programs and others.
We are excited about some new work in cystic fibrosis (funded by Emily’s Entourage) that appears to be promising and will hopefully lead to a clinical study. The ongoing work in TBI (severe head concussions) is quite robust in that we have projects focused on classic TBI at the University of Kentucky and Children’s Hospital of Philadelphia (CHOP). Still, we also have blast wave trauma research focused on the brain, eyes, and hearing. This research involves MP201, a slow-release drug similar to MPlOl. Our goals are to complete the preclinical packages and the GLP toxicology work to get an FDA-approved open IND to subsequently test patients with severe concussions. Of course, the ultimate goal is to obtain FDA approval for these drugs as a once-daily oral drug that activates compensatory pathways for survival as a disease-modifying agent for truly insidious diseases.
