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In the next edition of Sponsor Atlas: Discovering Biotech Startups, we’re looking at Mitokinin, exploring the current affairs and future orientation of this emerging San Francisco - based biotech startup. To accomplish this, we will give a business overview of their current operations, summarize their outsourcing needs, map out their development goals and decision-makers, and highlight their current strategies for capturing innovation. If you haven’t already read our other blogs on new biotech startups, be sure to check them out here.
Mitokinin Inc. is a San Francisco biotech startup focused on developing a novel class of kinase-targeted neo-substrates for the treatment of neurodegenerative and mitochondrial diseases. Currently their team is focused on leveraging endogenous repair mechanisms to drive disease modification in Parkinson’s Disease and Huntington’s Disease.
Mitokinin has a decent website with some good information, nice graphics and even links to their published articles, but overall we still had to do some research on our own to get the real picture of their current pipeline, activities, and on-going research efforts. The business was registered in Delaware as a C-Corp on 10/19/2017. Their principal place of business, as noted on the business entity search, is found at 953 Indiana Street, San Francisco, CA 94107, in which they’re a resident with the UCSF’s QB3-MBC BioLabs accelerator facility.
The MBC Biolabs location at 953 Indiana St. (formerly QB3@953), established in 2013, features 24,000 sq. ft. of lab and office space in San Francisco's Dogpatch neighborhood, just a short walk from the UCSF Mission Bay Campus. MBC BioLabs provides spaces as small as a single bench in fully-equipped labs. Scientists can conduct experiments on their first day, cutting months and millions of dollars off the time and cost necessary to gather data. MBC BioLabs’s facilities in San Francisco and San Carlos are home to 60 energetic young companies. Since opening its doors four years ago, MBC BioLabs tenant companies have raised over $1.8 billion dollars.
In June of 2018, Amgen and MBC BioLabs announced that Mitokinin won one of the Amgen Golden Tickets at MBC BioLabs, a highly sought after award for scientific success and recognition within the QB3 community. The company received one year of lab bench space and access to core facilities at the MBC BioLabs life sciences incubator, as well as connections to Amgen’s scientific and business leaders to help advance its scientific programs.
Mitokinin primarily operates at the QB3 facility, and our current estimates show they generate <$1M in annual revenues, and employ approximately 12 people at this single location. The information on the outsourcing needs of Mitokinin is few and far between, but their recent SBIR Phase 1 grant of $225,000 for their research on neo-substrate amplifiers of PINK1 for the treatment of Parkinson's disease is a good sign they have some capital to play around with for drug discovery, as well as outsourcing early preclinical work. Mitokinin is very close to reaching the IND enabling stage with one of their lead therapeutic candidates, but the company is very early in the development stage and they will be working through the usual steps for a while before reaching that stage with other products.
In order to provide some early-stage critical funding necessary for their startup technology, Mitokinin was able to raise $5M in private equity in October 2018 from a series of investors. This is a substantial amount of funding for Mitokinin, and they should now have the ability to quickly and efficiently move their research and development pipeline along the path to market with help from various outsourcing partners. On top of the private equity and SBIR funding, Mitokinin was most recently awarded in October 2019 a $300,000 grant by the Michael J. Fox Foundation for the advancement of their Parkinson’s Disease program, hence adding a huge bonus to their already hefty amount of capital to spend on outsourcing activities.
Mitokinin has combined a genetically validated target, a class of potent, highly selective small molecules, and a world-class scientific team to tackle some of the most critical unmet medical needs of our time. Neurodegenerative diseases affect more than 30 million people worldwide, and currently there are no disease modifying drugs for this, but Mitokinin aims to change that. They have an accomplished team of neuroscientists, chemists, pharmacologists, and business professionals all focused on one mission: delivering disease-modifying therapies for neurodegenerative conditions.
Any experience with research and development focusing on Parkinson’s Disease and Huntington’s Disease, and any new technologies surrounding these two particular diseases would be of tremendous benefit to Mitokinin at this point in time. Specifically, if your team has experience with in-vivo bioanalysis of mouse tissue samples and animal model development targeting neurodegenerative diseases; bioanalytical techniques such as IHC analysis, FACS and microplate analysis; or biochemical assays like Western blots, immunostaining, qPCR, and DNA subcloning, then Mitokinin should definitely be on your contact list, and you should be connecting with them for upcoming work in the near future.
Mitokinin’s Pipeline and R&D Focus
Mitokinin operates in the healthcare industry with a focus in biotechnology business. Launching medicinal chemistry efforts to generate kinetin analogs optimized for activating PINK1, their research team plans on developing novel analogs or optimized variants to treat Parkinson's disease, as well as potential therapeutics for other debilitating diseases. PINK1 is a master regulator of mitochondrial quality control. Mutations in PINK1 give rise to familial forms of Parkinson’s disease. Increased PINK1 activity rescues pathologies associated with neurodegenerative disease. Mitokinin has advanced small molecule therapeutics that specifically increase the activity of active-form PINK1. Importantly, Mitokinin’s compounds do not interfere with the endogenous regulation of PINK1.
Mitokinin’s lead candidate, MTK-458, has been extensively validated in in vitro and in vivo models of Parkinson’s disease. IND enabling studies are currently underway, and an IND filing is expected in 2020. In parallel, Mitokinin’s scientists are also investigating the activity of MTK-458 in models of Huntington’s disease, Alzheimer’s disease, and non-CNS diseases of aging where mitochondrial dysfunction is implicated. 
Mitochondria are well known for their role in generating the ATP our cells need to survive. What’s less appreciated, but critical to their role in neurodegenerative disease, is the role of mitochondria in inflammation, proteostasis, and cell death. Specifically, PINK1 is the cell’s surveillance system for damaged mitochondria. An unusual kinase, it only stabilizes in the presence of a depolarized mitochondrion; once stabilized, it activates a mitophagy pathway that leads to clearance of the damaged organelle. PINK1 activation has been shown to oppose the inflammation, mtDNA mutations, and metabolic/proteostatic failures that can lead to cell death in disease. Mitophagy, the process by which cells clear their damaged mitochondria, plays an important protective role in these circumstances: not only is the normal, healthy mitochondrial pool restored, but the proteotoxic species are cleared along with the bad mitochondria. Mitokinin’s scientists have shown that by potentiating the PINK1 pathway in times of proteotoxic stress, neuron health can be restored and disease-driving pathologies reduced or eliminated. 
- Daniel de Roulet - Co-Founder, CEO of Mitokinin, a veteran entrepreneur who has co-founded three companies across the technology and life sciences industries, Mr. de Roulet brings a background in finance and startup management to the Mitokinin team. Prior to founding Mitokinin, Mr. de Roulet co-founded and served as co-CEO at Knowify, a leading SaaS business management platform for contractors. He began his career in the financial services industry, serving as an equity analyst at LaBranche & Company before joining Bishop & Carroll Capital Partners, a long-short equity hedge fund. Mr. de Roulet graduated from Columbia University with a BA in Economics. 
- Nicholas Hertz, Ph.D. - Co-Founder, and CSO of Mitokinin, Dr. Hertz’s graduate research with Kevan Shokat provided the foundation for Mitokinin’s PINK1 program. Dr. Hertz leads a team of 12 scientists and research associates, along with 8 FTEs at CRO partners, pushing Mitokinin’s science and therapeutics forward. He has authored over 18 publications in journals such as Cell, Neuron and Nature. Dr. Hertz has been an invited speaker at international conferences including the Michael J. Fox Parkinson’s Disease Therapeutics Conference in 2018 and holds several patents. Dr. Hertz received his Ph.D. in Chemistry and Chemical Biology from UCSF with a Genentech graduate fellowship in the labs of Kevan Shokat and Al Burlingame. Following his Ph.D., he completed his post-doctoral training in neuroscience as a Helen Hay Whitney fellow in the lab of Marc Tessier-Lavigne at Stanford University. He graduated magna cum laude and Phi Beta Kappa from UCLA with a B.S. in Biochemistry. 
With a high-profile award under their belt, substantial research backing, considerable progress in scientific benchwork, and deep technical knowledge from their executives, we believe that Mitokinin will do very well in their early-stage developments and clinical trial studies. Mitokinin’s innovative approach to using precision therapeutics in specifically defined disease pathways will surely create some promising new treatments in the future. With their number of innovative programs in development using their unique kinase-targeting technologies, Mitokinin will potentially make some unprecedented discoveries in the field of neurodegenerative therapeutics and beyond.
Kinase-targeted drugs have been in development for more than thirty years and have made a large impact on the way we treat many human diseases. The great majority of these drugs work by inhibiting kinases through reducing or eliminating their signaling activity. Mitokinin is taking a different approach to targeting kinases, by aiming to increase the activity of active-form PINK1. The levels of active-form PINK1 are very carefully regulated by the cell. PINK1 only becomes catalytically active on the surface of damaged mitochondria. Mitokinin’s therapeutics only boost the activity of active-form PINK1, and have no effect at all on the regulatory processes involved in activating or degrading PINK1. This innovative therapeutic approach is inherently ‘light touch,’ unlike constitutively inhibiting an important kinase, Mitokinin’s drugs merely increase the activity of an already-activated kinase. 
Mitokinin is definitely on track to have some major innovations in the biotech industry, and it’s difficult to say exactly when they will come out of stealth mode, but we’re thinking it should be within the next few years, so be sure to keep them on your schedule and look out for our next edition in this series coming soon.
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