HUMAN PROOF OF CONCEPT

Nimbus Therapeutics is in the business of building structures. Molecular yes, but corporate too — they're unique and fit-for-purpose. CEO Don Nicholson explains it all: the partnerships, the code names, the high energy water, the bowling, the rapping. And how, at any given time, fully half of Amazon’s cloud computing power may be in use to create your next medicine.

Eric Schadt may enjoy the simple things in life — high velocity, a good polo shirt — but he is the first to admit that life is not simple. Living things are such complex systems, in fact, that our best chance to promote wellness is to understand them as vast information networks. To do so, Eric is unleashing maximum scale and bringing the firepower of math to bear. He endeavors to monitor and modify humans-slash-networks, both as CEO of the new genomics startup Sema4, and as Dean for Precision Medicine at the Icahn School of Medicine at Mt. Sinai. This episode was recorded in front of a live audience, on location - outdoors no less - at the Foundation2017 conference. Make of it what you will: as soon as Eric discussed god, the birds start chirping.

Alix Lacoste crossed the ocean from France in search of new challenges, made her way to California, ran out of money and took up filmmaking in community college. Insert the windy road that led to Neurobiology degrees from Berkeley and Harvard. Today she is a subject matter expert at IBM’s internal venture: Watson. You may remember IBM Watson from such disruptions as winning Jeopardy against humans in 2011. Now it is disrupting Drug Discovery as part of its effort in (human) health. Alix discusses some examples of how it’s tackling that challenge, including partnering with pharma companies and institutes to find unique disease genes. You might say there’s a new paradigm in genetics: Watson and Click.

Strong patent protection has always been a cornerstone of the biotech industry — and table stakes in a VC deal. But inter partes review has significantly changed the game in the last 5 years. Enter Scott Kamholz. Scott is once, twice, three times a doctor: Medicinae, Philosophiae, and Juris. He went from partner at a law firm, to patent judge, became a foremost expert in inter partes review, and then back to private practice at Covington & Burling with 250 IPR cases under his belt. Whether you’re a baby biotech with a patent license as your only asset or large pharma with marketed products to worry about, he is a good person to know. Scott is a great legal mind, but he cannot give a straight answer to a yes or no question.

If you work in biotech, or venture capital, if you pay taxes, or take medicine… you really ought to know the name Joe Allen. He worked tirelessly behind the scenes in Washington to get the Bayh-Dole Act passed into law. Sponsored by Senators Birch Bayh and Bob Dole, and passed at the last possible opportunity in a lame duck session of Congress in 1980, it is the legislation that realigned the incentives of the patent system to enable small biotech companies and their investors to flourish. And Joe's been implementing, overseeing, protecting, sharing, and blogging about it ever since. 

Deborah Dunsire was a general practitioner in South Africa when a motorcycle drove her into industry. And that side trip, ultimately routing her to Boston, is still going on. She built the North American Oncology unit at Novartis, launched Gleevec, ran Millennium after the millennium, realized the value in Velcade, took a foray into Forum, and recently announced her latest role, President and CEO of XTuit Pharmaceuticals. 

Art Pappas had an extensive, international career in the pharma industry before going on to form his eponymous VC firm in the 90s. Pappas Ventures has been partnering with pharma ever since: licensing assets from them, selling portfolio companies to them, syndicating with them, and managing venture funds for them. But perhaps most notable is the list of pharma and strategic limited partners they brought together to invest in their newest fund — Pappas V — it's a record, even for them. 

If the mantra in real estate is location location location, for venture capital it might just be timing timing timing. Stacey Seltzer made the move from big pharma into venture capital during a financial crisis and has gone on to build a wildly diverse portfolio of healthcare companies at Aisling Capital. She takes us on a tour of some of the highlights, and reveals what venture capitalists do for fun.

Marc was a podcaster before it was cool. That is, 2006. While producing over 100 hours of interviews on his show “Futures in Biotech” he confirmed his own future was in biotech, starting one and then another. Bypassing his jazz guitar talents and multiple black belts, he launched Aeromics out of Yale to develop the world’s 1st clinical candidate targeting a water channel for the treatment of brain swelling in stroke. And then there’s Dodo Omnidata, Inc. which is developing a read/write hard drive that stores data in DNA.

If Biotech Showcase is the farm team for JPM, then Sara Demy is the coach. She literally got high fives as her new conference burst onto the scene, bust out of its first two locations, and now boasts 400 presenting companies and 1,000 investors. And there are new offspring offerings in the Demy-Colton family as well...

After a run-in with Joe Biden’s entourage, Marty Lehr joined me on the first full day of the 35th Annual J.P. Morgan Healthcare Conference. He discussed his prior life at Osage University Partners, his current life at Context Therapeutics, and how his romantic life once dictated his professional life.

In 1999 Glen de Vries started a tech company in his 5th floor walkup - very much the NYC equivalent of a garage in Silicon Valley. Today Medidata Solutions continues to transform human drug studies with their clinical cloud platform. They are approaching 3M patients and a $3B market cap. Glen explains how he plans to reach escape velocity with no exit strategy.   And how he keeps his feet on the dance floor and head in the cloud.

Barry Kappel of Sapience Therapeutics and Gerard Honig of Symbiotic Health joined me for a fireside chat at the Foundation2016 conference.   Held at Cold Spring Harbor Labs, it was a beautiful day in pre-election times. If you listen closely you can hear local wildlife in the background: birds chirping and (the) James Watson roaring around campus in his Porsche.  I asked them about their startup companies, and after they critiqued the VC industry, I gave them a pop quiz. 

Moderna is the Kendall Square startup developing a variety of drugs made of messenger RNA, leaving your cells to translate them into proteins. Forging a new ecosystem doesn’t come cheap: in only 5 years, Moderna has raised nearly $2B and is valued around $5B. Its financial position may be the envy of its biotech neighbors, but it is also polarizing. It has generated intrigue and invited scrutiny, including in a recent article that questioned both the science and culture under its CEO, Stéphane Bancel. Quite the juxtaposition since it was just announced that Moderna is - again - one of Science’s Top Employers, and has even moved up in the ranks. What is going on over there? In this episode, Stéphane is the messenger. He takes us inside the how and why of Moderna.  

Today, Francois Nader is merely President of the Jesra Foundation, trustee of the New Jersey Chamber of Commerce, Chairman of Acceleron Pharma (XLRN), Director of ArRETT Neuroscience, Clementia Pharma, and Advanced Accelerator Applications (AAAP), and Advisory Board member of the Open Future Institute. But you might remember him from such former roles as President, CEO and Executive Director of NPS Pharma (NPSP now Shire) prior to its $5.2B acquisition, Venture Partner at Care Capital, 2013 Ernst and Young National Life Science Entrepreneur of the Year, Chairman of BioNJ, and Board member of BIO, Noven (NOVN), Trevena (TRVN), and Baxalta (BXLT now also Shire). He joins me to describe the art of being small while thinking big, and to share some decidedly unconventional wisdom.

Bill Newell is a lawyer turned large molecule wrangler. He’s CEO of Sutro Biopharma, and their special sauce - literally - lets them manipulate and manufacture antibodies with the kind of control scientists have had over small molecules for decades. Where other biotechs find scientific challenges can threaten their survival, with Sutro it comes down to strategic challenges. And Bill has led them to enviable partnerships, capital, and optionality. Sutro has an unfair advantage: Bill Newell.

Home or away, Brian Bloom is recognized for his wildly successful conference and boutique investment bank. With a mission to uncover and cultivate Canadian life sciences companies through scientific focus and range of services, Bloom Burton & Co., which he co-founded in 2008, has risen swiftly to be profitable and globally unique. And its Bloom Burton Healthcare Investor Conference achieved actual hockey stick growth since it broke onto the Canadian biotech scene 5 years ago. But hockey and cheerleaders do not go together. Brian’s knowledge of the Canadian biotech scene, and his seat on umpteen boards, leads him to a frank, no-apologies stance on the industry.  

Brexit isn't the only newsworthy and dismal problem out there. Consider a couple of others - some VCs would rather not touch them with a ten foot pole, yet Kate Bingham is taking a stab at them: There's Alzheimers. This past October, SV Life Sciences where she is Managing Partner, became the fund manager of the Dementia Discovery Fund. Launched with a charity and six pharmas at the table, and $100M in the bank, the fund brings a fresh operating model to the tired approach. And then there's gender diversity. Following the JP Morgan biotech investors conference this year, Kate co-authored an open letter to the industry, alongside Karen Bernstein of Biocentury. It queried why “the smart, dynamic women in our industry are forced to choose between demeaning themselves and making business connections.” Kate has the knack for looking at improbable problems and seeing a path to success. Perhaps because she herself is an improbability in the industry - having found her way into it 25 years ago, on account of a lucky phonecall and a mistaken post-it note. She joins me on this episode to talk closed deals and open letters.

Have you heard the one about the guy who founded a biotech startup in the middle of Manhattan? Around a repurposed, hydrolysable, insoluble small molecule? To treat massive strokes, traumatic brain injury, and other neuro indications? Using a highly translatable rodent model? During the financial crisis? Unpartnered? And who spent $1M per year to generate randomized, placebo-controlled, double-blind PhII results that show a 50% reduction in mortality from strokes that were too big for other trials and too late for other treatments? That’s Sven Jacobson. He is CEO of Remedy Pharmaceuticals, and was Partner at Carrot Capital Healthcare Ventures, the nontraditional VC that founded and funded Remedy. For a long time, Remedy was one guy and one drug. But that drug, Cirara™, combats swelling in the central nervous system - a root cause of morbidity and mortality in multiple diseases. Today Cirara™ is still investigational, but in line to be the first therapeutic advance in the stroke field in over 20 years. And an in-progress Ph II trial in TBI has it poised to tackle football as well. Sven doesn't have a swelled head - and he doesn't want anyone else to have one either.

Colin Cahill swears he didn’t grow up wanting to be a life science venture capitalist. But you would think he had planned it from his very first job cleaning glassware. His path from there to Venrock may appear linear after the fact, but at the time it was based on serendipity plus a hunch he should stay close to both science and business for as long as possible. In this episode, Colin deconstructs some of the great VC mysteries: How do they decide which deals to do, since “there’s no rules-based decision paradigm for venture investing”? Why, when other VCs have run screaming from med devices, has Venrock retained its breadth? And what does “falling in love” mean when a venture capitalist says it?

Greg Verdine has evolved from merely being a Harvard prof, to consulting for big pharma, to starting biotech companies, to being a Venture Partner, and even to co-founding a non-profit institute – not just sequentially, but largely in parallel. He has teamed up with Third Rock Ventures, TPG Biotech, AppleTree Partners, and he unveils his brand new gig with WuXi Ventures. Greg co-founded the biotechs Enanta (ENTA), Tokai (TKAI), Gloucester (now Celgene), Aileron, Warp Drive, WaVe (WVE), and Fog. His day job today, if forced to list just one, is CSO of Warp Drive Bio. He reveals a couple of secrets about Warp Drive strategy and lifts the fog off of Fog Pharma, his latest – and still stealth – newco. As different as these companies are, a common theme runs through them: to cure the incurable by drugging the undruggable.  With apologies to Star Trek, that is Greg’s personal mission: to boldly go where no drug has gone before. In fact Greg wants to blow up the conventional meaning for the word "drug". He sees beyond the pharma industry’s small molecules plus the biotech industry’s biologics, because they seem positively “puny” in the context of human biology. And he has clever tricks and other modalities at his disposal – not to mention the blueprints: 135,000 bacterial genomes, where the answers cannot hide.

In the late nineties, a company named "Advanced Medicine" came together with the 4Cs of entrepreneurship in place: a concept, co-founders, capital, and some well-placed cold-calls. Mathai Mammen was one of those co-founders, still living in a dorm at the time. The company's investors evolved, it renamed itself, went public, and ultimately split into two independent companies: Innoviva (INVA) and Theravance Biopharma (TBPH). Today, Mathai is the SVP of R&D at Theravance Biopharma. Under his leadership, they have always done things a little differently. In the beginning they used their seed capital to build an in-house vivarium. They have discovered all of their development candidates - 31 and counting - internally or collaboratively. And after 3 approvals, they left their royalty stream to Innoviva and struck out on their own to focus on R&D - because "it's difficult to be innovative when you're in the shadows." Mathai has had a longstanding reputation as one of the good guys in the industry, but in recent years he has doubled down. After two extraordinary family tragedies, he calls out the importance of persistence, humility, and empathy above all - both in and outside of business.

Ron Cohen has defied Venture Capital wisdom by founding Acorda Therapeutics over 20 years ago and remaining the CEO to this day.  Originally hearing "no" from 70 VCs, he nevertheless grew the company into a public biotech worth nearly $2B today.  As unlikely as that has been, there would've been no Acorda had he found more success on Broadway. Ron discusses his road from Jeopardy! champion to entrepreneur, the role played by his flat head and great hair, and what on earth could motivate someone to invest in drug development. He also explains how upstate NY does not start at 96th St. The two-part interview continues in the following episode, Part 2.

This past year, Ron took over the role of Chair of BIO, the Biotechnology Innovation Organization. From that vantage point, he comments on the high drama in 2015 that has entertained - and sometimes threatened - the industry. He discusses inter partes review, the right and wrong conversations on drug pricing, and the choices that determine the pace of R&D within our ecosystem of brilliant science and entrepreneurship. He also projects some hot trends and throws down the gauntlet for biotech in NY. If you listen carefully, you can hear him pounding the table. This episode, Part 2 of the two-part interview, picks up where Part 1 left off, on the subject of social media's role in biotech.

Welcome to Human Proof of Concept, the Biotech Venture Capital podcast hosted by Janelle R. Anderson.