Tear Sheet: Cohbar Inc. ($CWBR)

Bacteria are prokaryotes. Animal cells, fungi and plants are eukaryotes. Prokaryotes tend to be acellular and lack nuclei, while eukaryotes strive towards multicellularity and specialization, and have highly organized nuclei. The life objectives of eukaryotes require lots of energy in the form of ATP.

Back in the mists of time, millions of years ago, bacteria took up permanent residence inside eukaryotes in a commensal or mutualistic relationship. The bacteria would get permanent shelter and nutrients, and the eukaryotic cells would get a permanent continuous safe supply of ATP energy in the form of between 500 and 100,000 bacteria living stably within each eukaryotic cell. These bacteria would be renamed mitochondria. (In plants they are called chloroplasts).

The mitochondria have their own DNA genome and reproduce both in an autonomous way inside each cell as well as in a manner performed in concert with a diplomatic relationship with the nucleus. Your mitochondria come almost exclusively from your mother, and this may be part of the driver for so-called maternal imprinting, the fact that a mother leaves her mark on offspring more than the father does. Mammals reproduce sexually, when sperm and egg fuse. An average human ovum has about 100,000 mitochondria. At fertilization, the midpiece of the spermatozoa, but not the head or the tail, enters the ovum. The midpiece has about 750 mitochondria. Thus if all your mitochondria don’t come from your mother, more than 99 percent did.

The mitochondria are mere dots within each cell, barely visible, but their presence within us may have helped drive evolution of our species to its sophisticated present form. The Liliputian here is the Brobdingnagian: mere dots within us, but they are our essence.

Over millennia, the intimacy between eukaryotes and their mitochondria grew. While the mitochondrial genome became smaller than those of ancestor bacteria, it also added new genes for servicing its master. Mitochondria took on roles not only of providing ATP but of caretaker functions. Mitochondria began to secrete “tune-up” peptides that optimized metabolism and organ function. Mitochondrially-derived peptides (MDPs) are tonic and trophic factors that restore our health.

Although we rely innately on mitochondria for our survival, they tend to lose 75 percent of the ATP generating capacity they had at our birth by the time we are 25. Despite this, we know that much of the driving force behind long life may be because certain centenarians retain higher levels of MDP expression late in life. We’ve also begun to appreciate the idea that certain diseases may be “mitochondriopathies,” may be diseases of mitochondria in the cells of the ailing organ. Non-alcoholic steatohepatitis, Alzheimer dementia and many forms of congestive heart failure, for example, may be diseases driven by mitochondria of the liver, brain and heart.

CohBar Industries, now publicly traded as $CWBR, was founded in 2007 by colleagues Pinchas Cohen, MD, and Nir Barzilai, MD, both aging researchers on opposite coasts. Harvard aging researcher David Sinclair, PhD, is also a co-founder. CohBar is now headquartered in Menlo Park, California. Management recently welcomed Cleveland and me for a comprehensive visit that included in-depth interviews with all of the officers and a tour of facilities, including the laboratories. Following that visit, I also met with CohBar board chairman Albion Fitzgerald in New York City; at this writing, I have just completed a visit with co-founder Nir Barzilai, MD, at Einstein Medical College in The Bronx. These interviews will be presented in a longer column on CohBar soon.

One of CohBar’s secret weapons in Chief Scientific Officer Kenneth Cundy, PhD, a veteran of Gilead Sciences and Xenoport. Cundy, who is British, has more than 77 publications, more than 100 international patents, and has been behind 15 INDs and 5 NDAs. Cundy developed HBV drugs adefovir and tenofovir at Gilead as well as antiviral agent Tamiflu.

CohBar owns an intellectual property estate of 65-100 MDPs, all of which may have relevance in human therapeutics, but not all of which are yet characterized. CohBar is the only “mitochondrial therapeutics” company in existence. It’s famously thrifty: CohBar has no debt, had $12.5M cash on hand in July 2017 leftover from cumulative capital raised of $29.6M and has completed IND-enabling studies of a lead MDP product proposed for human trials as a therapeutic for NASH and dysmetabolism. Since when has a company gotten to an IND after spending merely $17.1M?

CohBar cofounder Nir Barzilai, MD, a renowned endoscrinologist at Albert Einstein College of Medicine is one the world’s elite aging science researchers. Barzilai draws a distinction between longevity, which is how long you survive, and the subset of that during which you live in a state of cardinal health, free of age-related disease. “Aging” here includes clinical situations in which cells, organelles and organs behave as if they have aged even if their host has not. In many senses, a 30-year-old with type II diabetes has an aging-related disease. Barzilai advocates extending both longevity as well as the harder to accomplish task of living without age-related disease.

A locus of aging-related disease is the mitochondria and their lifelong output of caretaker peptides. For example, Barzilai has published intriguing data that what distinguishes centanarians from people who die younger is that centanarians bear higher levels of mitochondrial peptides. Non-alcoholic steatohepatitis (NASH), Alzheimer dementia and many forms of congestive heart failure, for example, may be diseases driven by mitochondria of the liver, brain and heart.

CohBar’s mission: Increase healthy lifespan with mitochondria-derived peptides as drugs, as therapeutic agents targeting age-related diseases. CohBar is addressing the enormous unmet medical needs of our aging population. CohBar moreover is the first biotechnology company to address mitochondrially-driven disease with mitochondrially-based therapeutics.

CohBar’s proposed mitochondrial peptides as therapeutic agents are small, no more than 25 amino acids, and are “optimized” by the company to make them more pharmacokinetically ideal and deter proteolysis within tissues. This methodology is proprietary. They’ll be given as subcutaneous injections.

A study of CohBar’s lead peptide in overfed mice will be presented during the third week of October 2017 at AASLD in Washington, DC. Mice in the study were obese, dyslipidemic, insulin-reistant and with severe NASH. All these pathologies abated with twice-weekly subcutaneous peptide injections. MDPs are generally 20-25 amino acids in length. We plan to attend the poster presentation.

CohBar plans to submit an IND for this lead agent peptide as a NASH therapeutic during 1Q18. Although the peptide will need customary phase 1 trialling, the company will likely conduct phase 2 as a series of secondary, exploratory endpoints to assess whether this agent might have a role in treating obesity, dyslipidemia, and insulin reistance in addition to NASH.

According to CohBar CEO Simon Allen, CohBar is actively seeking partnering arrangements for the development of each of its major products. Allen views partnering, ideally encompassing both a sharing of development expenses and cash up front to CohBar, as an ideal means of preserving $CWBR shareholder value.

Because CohBar is now just emerging in the clinical biotech scene, and because it now faces a catalyst- rich six months, we present the stock for your consideration and regard it as among the most compelling long investment ideas ever uncovered by us here. It’s time to embrace certain human illnesses as mitochondrially-driven pathologies and treat them accordingly. CohBar is the sole biotech company proposing to treat mitochondrial pathologies in a manner informed by a profound knowledge of mitochondrial behavior.

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