A Table Worth Pounding: The Slam-dunk Long Case For Cohbar ($cwbr)

With glasses raised, “Tsin tsin!” from BioPub to the leadership of CohBar (from top): Chairman Albion Fitzgerald (designated “Best Biotech Board Chairman” by BioPub); Interim CEO Philippe Calais, Pharm.D., Ph.D.; COO Jon Stern, MBA; CSO Ken Cundy, PhD (designated “Best Biotech Chief Science Officer” by BioPub); co-founder Nir Barzilai, MD, Professor of Medicine  and Genetics at Albert Einstein College of Medicine.

We’ll give ourselves a little credit: when we initiated coverage of CohBar ($CWBR) with a concise column on it in the fall of 2017, appearing in the predecessor forum to this website (and housed in BioPub archives), we did so in the context of considerable expenditure of shoe leather pursuing our quarry.  I’d had an invigorating conference call with management. We connected well, indeed we resonated. I’m something of a mitochondrial biology autodidact, having ingested perhaps 1000 original studies on the subject in the last 7 years, and CohBar’s team seemed gladly caught off guard that an ostensible stranger needed little coaxing and grasped immediate merit in their plans. The conversation placed me in a kind of cognitive epiphany because I was thrilled to realize someone planned finally to harness the mitochondrially elaborated family of peptides, not a new subject but still an underexplored one,  for human therapeutics.

Boots on the ground. TSA security checks, lots of them. Uber rides (and intermittently psychotic Uber maps on smartphones). Two-star hotels with soap that lathers only begrudgingly. It was to become our new standard of coverage at this forum….something no one else in the biotech analyst’s game does and what we regard as the only authentic means of getting at the truth, inasmuch as in direct encounters, 97 percent of message is non-verbal, not conveyable by phone or email and tough to capture on Skype.

Shoe leather: I had a kind of encore phone call with CohBar management, sensed a scientific revolution might be imminent and conveyed an urge to visit. I encountered no resistance and the next day was booking passage to Menlo Park, California, where the company’s headquarters and research facilities are housed. Perhaps the greatest feature of our forum here is our discussion threads, for which only “palimpsest” is le mot juste (consider looking up “palimpest” and you’ll get why I use that word). They are sociable candid discussion threads premised on their contents being ever en famille, and like the ragas of Indian sitar music, they go ever on and on. In a thread I casually mentioned plans to visit CohBar. Soon, then-reader now-contributing editor Cleveland reached out to me privately and expressed an interest in accompanying me. Cleveland is a “quant,” a credentialed hardcore numbers-driven financial analyst who once traded portfolio equities for George Soros. I welcomed him. CohBar had evoked his attention because of the “juvenescence” movement and its promises as an investing motif.

It wasn’t difficult for the people we met, COO Jon Stern, then-CEO Simon Allen, CSO Ken Cundy, PhD, to impress us: they reek of credibility, accomplishment, know-how and grace. Gilead ($GILD) alumnus and tenofovir inventor Cundy particularly left an indelible impression: biotech ur-veteran, trenchant scientist with consummate experience, a man with bragging rights in that his work has informed an NDA tally running well into double digits (only Cundy never brags….has no need to). Jobs for people with Cundy’s reputation are hardly difficult to come by; what  mattered is that he’d chosen THIS one, that he felt that mitochondrial peptides and bringing them into the clinic could slake both his considerable curiosity and also his love of accomplishment.

Stern  wrapped up the day in warmth and a restrained exuberance. He was insistent that I meet chairman Albion Fitzgerald, a highly successful serial IT entrepreneur and early backer of CohBar, on home turf NYC. And about three weeks later at a circuit NY fall biotech institutional conference, Fitzgerald pinged my cellphone at precisely the agreed-upon moment; I met him in the hotel lobby. Even the not-easily-impressed tend toward being caught off-guard by Fitzgerald: lean, tall, dressed to the nines, sporting a Karl Lagerfeld ponytail gently graying like the rest of his full head of hair, blue eyes punctuated by wire-rimmed spectacles. During the vivid, tete-a-tete conversation that followed and spilled well beyond its presumed allotted time, I realized quickly that I’d be transfixed by my mind’s own rendition of Fitzgerald for the rest of my time on earth: Fitzgerald is kind and it’s never fake; he asks how you’re doing because he actually wants to know the answer. Fitzgerald is a polymath with an IQ of 180 who regaled me with how he’d sat monastically for six months with mountains of papers on mitochondrial biochemistry to see if he could attach credibility to the claims of Cohbar co-founders Nir Barzilai and Pinchas Cohen, both physician-investigators….to interrogate the field to his own satisfaction and to see if making a major investment in the start-up company felt right to him. An image of Fitzgerald as retread mitochondrial scholar passing languid afternoons in lotus posture at his farm in New Jersey is etched in me; he’s flipped 300 pages since lunch and yet is still cool-breezing it ahead, his brow furrowed only because receptors of curiosity in his brain have seldom found agonists as potent as the affairs of mitochondria.

Perhaps a week later, Stern called again. Stern is clever enough to have known I’d get along with Fitzgerald like a house on fire; he wasn’t sniffing around about that. He wanted to gauge my appetite: was I now CohBar-sated or merely CohBar appetite-whetted? In short order, I found myself Ubering from midtown into the Bronx….to Yeshiva University, to Einstein College of Medicine, to the research labs of the life-affirming and portly Nir Barzilai, MD. Barzilai’s resemblance to singer Paul Simon is more than passing. Barzilai kicks interpersonal genuineness up to an arch level….to spend 20 minutes with him (and I spent a whole afternoon) is to feel as if he’s admitted you to his inner circle. Barzilai’s musings are thick with anecdote: his education in Israel, his training in London under hepatologist to the gods themselves Sheila Sherlock, his fundamental work into the biology of aging, his interest in metformin, his early data leading to the discovery of MOTS-c (of which lead agent CB4211 is an analog).

If you get a sense that I could write a nonfiction novel about becoming an advocate for and an investor in $CWBR, you are perceptive. For me, these are people who have long since stepped out of biotech’s Proscenium arch and become real to me as people, as friends, as colleagues. Sitting across a table from any of them carries as much psychic significance for me as sipping tea with a venerated aunt or dining with a friend I’ve known for 40 years but not seen in 10. CohBar does not offer for them mere employment or distraction. Why? Perhaps because quality people like them are drawn to exceptional, singular situations.

Analysis of the mitochondrial genome shows it could potentially encode up to 100 short or medium length peptides that don’t seem to act on the mitochondria themselves. They are outbound, emerging late in the day, as it were, of the storied history of the mitochondria. This is particularly meaningful when you consider how “fast cycling” prokaryotic mitochondrial DNA is compared with our more cumbersome eukaryotic DNA as mammals. Imagine the most social media-immersed person you know, his or her mind a tabula rasa acting in receptive immediacy for every new hot turn of phrase, fashion and meme that bubbles up from within our culture. Mitochondrial DNA is kinda like that: labile, responsive, attentive, it evolve-mutates seemingly in sympathetic resonance to the needs of its hosting organism, which is eukaryotic and multicellular. The mitochondrial genome is agile…able to accomplish change in days to weeks that would require tens of thousand of years for eukaryotes to accomplish.

“Only deadly in a swarm” is a refrain lyric from a 90’s hit single by Seattle alternative grunge band Soundgarden. If my life were all on a VHS tape and you rewound that tape, the first scene comprising my earliest memory has me on a farm in Appalachia. I’m wearing toddler shorts on an early summer day and playing along a stone fence constructed by my grandfather. I notice buzzing small yellow entities funneling themselves into a place up under a large stone and, having a curiosity appetite like a whale’s for krill, go to investigate. But I see little and decide to probe up under the rock with a stick.

In my next memory, the world’s orientation seems askew….as if I am horizontal. I am moving, hurtling through space, even noticing a breeze in my hair. My body is flying to my grandfather’s farmhouse atop this hill. I am not in pain but my legs feel strange and tingly and I feel euphoric.

The yellow entities were Japanese hornets. Through some eerie miracle of female intuition and maternally-driven quantum entanglement, about 2 seconds before I’d begun screaming, my mother had sensed that something terrible was happening. And had looked up from pruning a shrub. My poking around had incited a swarm, and I’d been stung well over 100 times….I probably felt no pain because of endorphin release. My parents had run to the scene, and oblivious to the yellow tornado and insect pheromones of aggression around me, had rushed in, scooped me up and frog-marched me on the hustle into my grandfather’s screened-in porch area.

Why do I recall this story here? Because of its powerful metaphor. None of those hornets acting individually could do anything but respond in rather dumb reflexive fashion to ambient pheromones released by others and acting in a kind of insect-paracrine fashion. Ah, but COLLECTIVELY, think again: they had taken on a kind of quaternariness….insect synergy. Acting as a strength-in-numbers entity, they’d stung me mercilessly to protect their nest, and had succeeded in immobilizing me. None individually had the capacity for making decisions to this kind of behavior, or the imagination to execute it….and neither do their individual capacities precisely add up to their will to action, how to stage things and malevolent firepower acting as a collective. “It is very generally UNTRUE that things are equal to the sum of their parts,” Poe once wrote…and he could have been speaking of mitochondria. Even for us now, how the mitochondria congeal their will into a collective synthesis of mission that seems to have a grasp of the needs and urgencies of highly complex organisms that utterly outstrips anything science can do, drawfing our understanding: for me I am left having to stand in awe because no other action or sentiment suffices. From high school surely you remember Walt Whitman’s mocking of the learn’d astronomer and Whitman’s soul-satisfying remedy for it: looking up in perfect silence at the stars. Sometimes being with mouth agape is the most intelligent facies to show the world.

When we placed CohBar in our stable of followed companies, we did so with two-fold thrusts in mind: first, that it would likely be an ever-fixture of our attention, and second, that because of the lofty qualities of its people and integrity we’ve seen in how it conducts itself, that it would ever warrant radiant, even impassioned coverage and advocacy as an investment. The extreme and even preponderant relevance of mitochondria to human disease has only recently begun getting grasped, but the ramifications are that it will be a permanent paradigm for the clinic….even if messages such as those of CohBar seem at first blush to be so arcane, so counter to what we thought we knew, at times even so philosophically elusive as to require extended time to engraft in listeners. The amazing recent work of firms like Reata ($RETA) and Minovia Therapeutics vividly underscore that a mitochondrial mindset is here to stay in medicine. That disease, that syndrome, you know, the one that has so long vexed doctors as to its origins and its drivers: are you sure it’s not a mitochondrial pathology?

Which makes the recent ostensible hit piece on CohBar that we all know about, the elephant in the room, appearing in Seeking Alpha somehow at once poignant and even more ludicrous than you might first think…poignant because it’s probably harmed morale at a fine company, and ludicrous because its vapid sound and fury fall flat and signify nothing, failing to connect meaningfully on even a single contention. The author is one we know well; we’ll not name him here and neither will we disparage. His work disparages him enough already, but ad hominem bashing we leave to the porcine trolls and troglodytes of social media, nearly all of it debased and seldom rising to worthiness of contemplation. The same could be said of the publication in which the article appeared, ever rife with misconstrued facts and uncorroborable statements. We are certain the author of that piece has never visited CohBar, never spent any time with its principals, never attended one of its presentations at either investor or academic meetings, and likely never exercised himself enough to pick up the phone. He wrote one piece for our publication here, after which we chose to end our relationship with him because remedying the insipid prose and underwhelming contentions would take more time than writing a decent acceptable column from scratch and because we are not a rehab facility for writers. We don’t do editorial co-dependency here. If our editorial board regards your work as not placing you in contention with the credible big boys of this game, sorry, we’ve no seat at our table for you.

Why this author chooses to fight this particular battle is a mystery to us. He possibly resents how we discovered CohBar before any other publication seems to have and, being utterly untrained and incapable of seeing what we see in its IP,  bristles at our enthusiasm for it. Bullies torment the innocent dog of the nice neighborhood kid they regard scathingly.

But as to his contentions, let’s dispense with those. First, an allegation of leadership instability. This assertion is a long way from true, and let us tell you why. Some years ago, in the lead-in era to terrorism’s new age of trust-no-one incivility, I was mesmerized by a network TV interview with the security chief of Israel’s El Al airlines. The firm had a spectacular safety record, decades since it had sustained a terrorism incident. Why? Human intelligence, the security chief said. Relentless interviewing of passengers so that their urges, motivations, intentions and notions might be divined; primates are good at scanning one another and achieving a kind of intuition-driven mind reading even in the absence of words. Thus my original mention of shoe leather ever recurs: in spending extended time in the company of CohBar, we sensed things were less than ideal with the former CEO. We mean him no harm with that statement; we like him, know him to be mannerly, and have had many fine conversations with him during the last two years. But it was his first gig as CEO and he brought to the post a kind of administrative immaturity. We sensed vividly  that his tenure simply wasn’t going to work out. We felt that saying so did not belong in print, and we also felt the company ran in those days in the form of a high-functioning oligarchy. We regard Albion Fitzgerald as the best board chairman in biotech because of his sense of fiduciary duty to shareholders. Fitzgerald resides officially on the east coast, but has logged relentless hours over the years at CohBar headquarters doing what he does extremely well: running business, seeing after things, paying attention to detail.

Having said this, that perhaps the prior CEO did not represent full-blown liability to CohBar given its chairman’s sense of responsibility, was it a mistake ever to have hired him? Well, we think that retrospectoscopy is a tool for molling cognitive dissonance. But let’s be very clear, even blunt: Was Mr. Allen’s orchestrated departure from the company a manifestation of chaos? Did it incur entropy? Hardly, in that his departure appears to have been to make way for Dr. Calais. Calais’ rise to power at the company occasions a containment of entropy, gets the company on right footing. This was not damage control folks. Our take is that CohBar now feels led, led with inspiration. If the company was never rudderless, it now has a highly desirable, visible, compelling helmsman….and this should occasion celebration and share buying, not the casting of aspersions.

Our take? Had the powers that be at CohBar chosen to replace Mr. Allen earlier that would have appeared even more unstable than replacing him now. And we tend to feel that having Mr Allen not quite rise to the occasion of adequately messaging the company did no harm in its amorphous preclinical years. But now it’s time to get going in the clinic for this firm, and the firm has hitched its destiny to Dr. Philippe Calais. We met with him in early January…..and we felt the board has made a brilliant choice in appointing him interim CEO. As always, CohBar has never selectively disclosed to us ANY non-public information about the company, but as humans who have logged time around the company, we intuit Dr. Calais is likely to be appointed permanent CEO this year. It seemed clear to us that Mssrs Stern and Fitzgerald feel at ease around him, that they regard him as leavening company matters and being usefully prepossessed with an authentic charm and charisma. Calais is a wonderful man, frankly. As a shareholder I endorse him heartily and think you should,after considering the matter, consider doing so too. Meanwhile, “instability” at the top? What has happened is positively providential…..indeed it is the best possible outcome and places CohBar on vastly  superior footing in 2019.

Another contention was that clinical programs had run aground at CohBar. Again, quite some distance from the truth. When the company voluntarily placed CB4211’s phase 1 trial on clinical hold, we covered that matter fully by publishing an interview with CSO Cundy (consider re-reading that item). We feel the issues are well in hand, highly surmountable….and that progress on this front got snagged by the recent government shutdown, the FDA placing itself in slow mode. We have heard nothing that threatens to derail CB4211 development.

Let’s use CB4211’s mention as an opportunity to review its vast relevance. Mitochondria are the stars within us. Each of your cells may have 100,000 of them, and they are by identity bacteria, likely originally rickettsial, that took up permanent residence in us millions of years ago, arguably not long after the advent of oxygen in any abundance on earth, to service ATP-based energy needs. But the relationship between “us and them” is vast and nuanced, and on many days a strong case can be made that we are more them than we are merely a eukaryotic us. The relationship is highly mutualistic; indeed the mitochondria have delegated some of their formerly autonomous functions over to our nuclei in a gesture of intimate farming out. Our nuclei and mitochondria are always engaged in intense dialogue in a language premised on more than 400 communicative proteins…..and our understanding of that communication is still quite primitive. It won’t always be so.

What we do know is this. Mitochondria make ATP for us. And they constitutively elaborate what I’ve taken to calling caretaker peptides, lots of them….pharmacologic agents that act in endocrine and paracrine fashion to optimize our health. Many lines of evidence have it that by age 25 we have forfeited 75 percent of our mitochondrial function (perhaps some day we will learn how to retrieve that). That means that by 25, we also have begun the long slow process of meaningful disappearance of the caretaker peptides, too.

Cundy’s brilliant work, first unveiled at ADA 2018 in Orlando, which I attended as your eyes and ears, shows MOTS-c analog CB4211, the company’s first drug candidate, to be an allosteric modulator of the most needed sort for the insulin receptor. It’s as if our insulin receptor still exists in a V1.0 of itself, and over the ages has come to count on co-presence of MOTS-c for ideal non-resistant behavior. The disease that stalks all of us as we age is insulin resistance. Now you see why: by age 25, if you’ve lost 75 percent of your mitochondrial function, MOTS-c levels are no longer nearly where they ideally should be. And so begin the age-related processes of weight gain, of dyslipidemia, of formal insulin resistance eventuating in outright glucose intolerance. NASH is purely an insulin resistance phenomenon. Thus you cannot miss the greatness with which CohBar’s current work is imbued: a cure for the cardinal disease of mankind. By replacing MOTS-c function, by giving CB4211, we can not only reverse NASH and its fibrosis,  but also dyslipidemia, insulin resistance and obesity. A new goal of DM-II therapy might become—not ever-chasing glucose levels—-but reversing the DM-II phenotype entirely by rejiggering insulin receptor sensitivity back to where it was when you were 16 and felt invincible and ready to take on the world. Part of that latter statement is getting off all that stubborn weight driven by hyperinsulinemia, driven in turn by insulin resistance at the receptor level (by “deficiency” of MOTS-c as we age).

The carpetbagging hit piece on CohBar also tried to foment trouble on the basis of a hollow claim of overvaluation. CohBar market cap now sits at around $130M. Knowing, however, that the company has a second peptide, an analog of humanin, deep in pre-clinical development and that it may, based on preclinical models, have anti-Alzheimer’s activity in that it appears to reverse amyloid-driven neurotoxicity, should shake the foundations of medicine. Two remedies, both potential blockbusters, against an IP backdrop that easily conjures prospective valuations of billions of dollars: this easily justifies present market cap which we already regard as unsuitably low, not high.

Ask any clinician what bedevils the human lot. Much of it is preventable, being the consequence of mankind’s love of self-abuse. But the inexorable juggernaut stalking everyone reading these words is insulin resistance and its many manifestations. Try as you might, one way or another it WILL claim you, even contributing to the cancer, strokes and MI’s you may experience. If a disease is THIS ubiquitous and inherent in the human race, is there any way to place a pricetag on the one technology that can clearly contain it and the one company owning exclusively that technology? Market cap too high? What is too high for CohBar? A market cap that subtends potential future sales in the double-digit billions of dollars is certainly not too high….though it is utterly wasted on Seeking Alpha‘s purposive near-mendacity how far CohBar’s present market cap is from such a valuation.

Given the brutarian denigrating nature of markets in recent months, particularly affecting small-cap biotech, suffering as things are from paucity of capital, a certain imprimatur accrues to CohBar for keeping market cap above $100M in the absence of any phase 2 program. Institutions have overtly demonstrated time and again for two years their reluctance to enter even highly auspicious situations in the absence of clinical data. Without giving advice or intending to, what we see is a buying opportunity of unusual profundity. For me selling shares here, as the misguided Seeking Alpha author advocates, makes as much sense as inserting your hand into an open flame and not expecting that agony and charred flesh will ensue.

This is certainly not the only time you will hear from us this year about CohBar. And we admit we worried about stooping to respond to salacious de classe banter about the company, especially when wielded as irresponsibly as it has been. Yet that blather, that bloviating offal, is easy to refute comprehensively with an economy of words. Meanwhile, we lament that it is not a crime for certain authors to be stupid and sometimes wish it was. We defend companies in our stable so long as they continue to be the elite companies they were when we initiated coverage. CohBar is more elite than ever, with a fresh new face at the helm who will prove able and be like wind in company sails. We suspect the company is casting about for a CMO and will recruit a gem. We fully expect resumption soon of CB4211 clinical trials. As always you’ll know as soon as we do. We foresee a fine year ahead. And we adore this company more than ever.

Disclosures: BioPub has not been compensated by CohBar to publish this column or for its opinions expressed on the company now or at any prior time. The author holds a long position in $CWBR and $RETA shares and has never sold any shares of either. He will refrain from trading in these shares for 7 days reckoned in business days after this column appears. Copyright 2019 BioPub and the author. May not be reproduced without permission. This column is intended as neither advice nor solicitation for any reader to trade in any equity, and while intended to jump-start one’s own personal due diligence before investing, is no substitute for it. The author is grateful to Dr. Helen Ong and Managing Editor Allan Lee for helpful discussions, and to Mr. Lee for photo editing this column in post-production.

Corrigendum: because of a server error, the version of this column originally posted bore a number of corrected errata never transposed into its final copy. A new version was posted around 8 pm correcting those minor errors.

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