13
Jun
2019

Who Will Be the Next Celgene of Dealmaking? VCs, Entrepreneurs Size Up Partners

Stars aligned beautifully, not long ago, for dealmaking at Celgene.

The company, early this decade, was raking in the dough from the multiple myeloma drug Revlimid. Cash had to be spent somewhere.

Celgene didn’t have much of its own R&D. Shareholders weren’t clamoring for their cut, via quarterly cash dividends. The stock soared, without any jet fueled-share buybacks. Letting cash pile up in the bank, collecting puny interest payments, didn’t make much sense.

Rarely are companies so fortunate. Even more seldom, the company had senior executives who were willing, and empowered, to aggressively execute on a historic partnering spree.

Celgene in the early part of this decade had George Golumbeski in business development and Tom Daniel in early R&D. Both were scientifically minded, and business savvy. They saw a renaissance going on with gene therapy, cell therapy, genomics, targeted cancer drugs. They saw eye-to-eye. They had the support of their boss and the board.

The result: Celgene built a network of 50 collaborations across immuno-oncology, immunology, neuroscience, epigenetics, protein homeostasis and more. Agios Pharmaceuticals, Bluebird Bio, and Acceleron Pharma are a few companies that owe much of their success to an early lift from Celgene.

Nothing lasts forever, though. Bristol-Myers Squibb is putting the finishing touches on its $74 billion mega-acquisition of Celgene. Golumbeski and Daniel have moved on.

Paul Biondi, the senior vice president of business development and strategy at Bristol-Myers Squibb, is well-regarded in biotech innovation circles. He is keeping his job and influential position reporting to the CEO. That’s good news in innovation-land. But nearly everyone in biopharma expects at least a few months of merger-related indigestion to distract the BMS/Celgene team into 2020. Those are sub-optimal conditions for beating out pharma competitors who also want to acquire the hottest platforms and products that biotech has to offer.

So…who in Big Pharma/Big Biotech is poised to become the “new Celgene?” Who has the money, the desire, the humility to lean on innovative little partners for help, and the senior executives with the necessary guts?

Licensing data from the past year, via Informa’s BioMedTracker (see table below) suggests that Gilead Sciences, Genentech/Roche, Eli Lilly, AbbVie, and Biogen are companies to watch, at least in terms of number of deals done over the past 12 months. But there’s more to the story, which I sought to flesh out via conversations with venture capitalists, biotech executives, and a few pharma insiders.

Read on for an inside look at some of the candidates for “most aggressive” in biopharma business development. If you’re lucky, you might be able to schedule a meeting with someone from one of these companies at BioPharm America, coming up Sept. 11-12 in Boston. REGISTER HERE.

Read the full article HERE.

13
Jun
2019

Predicting Who Will Benefit from Cancer Drugs: Liz O’Day on The Long Run

Today’s guest on The Long Run is Liz O’Day.

Liz is the founder and CEO of Cambridge, Mass.-based Olaris Therapeutics. This is a scrappy little startup that’s studying metabolites that could provide clues for predicting which patients are most likely to respond to certain cancer drugs.

Liz O’Day, founder and CEO, Olaris Therapeutics

Figuring out which patients are likely to respond is one of those perennial challenges of the cancer therapy enterprise. Given that most patients still aren’t helped by the best drugs we have to offer – and all of these drugs are expensive and come with side effect baggage – there’s a need to use our increasing knowledge of biology to cut down on the waste.

It’s about getting the right drug to the right patient – or at least stop giving the wrong drugs over and over.

There are companies looking through the lens of genomic mutations. There are companies looking to protein biomarkers. Olaris is seeking to make its niche with analysis of metabolite signatures. In the early going, it has focused on the kind of metabolites that can indicate likely response to the CDK 4/6 inhibitor drugs for HER2 negative breast cancer.

Liz is both a scientist and an entrepreneur, unafraid to buck conventional wisdom. She’s undeterred by the skepticism and eye-rolling that sometimes comes up in meetings when you utter the words “biomarkers” or “metabolites” or “diagnostics.”

I met Liz by chance at the Biden Cancer Summit in Washington DC last September. I thought – she has an interesting story, and is working on an interesting problem. Maybe I should have her on The Long Run. She and her team went on to present some interesting data at ASCO.

I think you’ll enjoy listening to Liz describe the technology, her strategy, and how she got on this track.

Now, please join me and Liz O’Day on The Long Run.

22
May
2019

From Open Biology to Pharma Leadership: Jay Bradner of Novartis on The Long Run

Today’s guest on The Long Run is Jay Bradner.

Jay is the president of the Novartis Institutes for Biomedical Research (NIBR). This is one of the heavyweight organizations in Big Pharma industry R&D. When Novartis planted this operation in the heart of Cambridge, Mass. more than a decade ago, it was the start of a trend toward Big Pharma R&D operations nuzzling up in close proximity to the academics, the startups, and the VCs who live in the Harvard/MIT corridor.

Jay Bradner, president of the Novartis Institutes for Biomedical Research. Photographed at the Boston Cancer Summit, Mar. 7, 2018

Bradner, before taking on this high-powered job overseeing 6,000 drug discovery employees worldwide, operated on the less wealthy, but highly creative, academic side of Cambridge bio-land. He was on the faculty at the Dana-Farber Cancer Institute. He became known for his advocacy of open-source biology. Neither of these things were conventional resume-building activities for a traditional candidate to run NIBR. For one thing, he had never led an organization bigger than your standard academic lab.

In this conversation, you’ll hear a smart guy with a lot of boyish enthusiasm. You’ll also hear someone who’s well aware of the many things he doesn’t know, and the humbling magnitude of the challenges in biomedicine.

Now, please join me and Jay Bradner on The Long Run.

8
May
2019

An Elephant for Immunology Drugs: Sheila Gujrathi on The Long Run

Today’s guest on The Long Run is Sheila Gujrathi.

Sheila is the CEO of San Diego-based Gossamer Bio. This immunology drug developer is an example of what I’ve lately started calling an “elephant” startup (see February TR coverage of Maze Therapeutics for another example).

Sheila Gujrathi, co-founder and CEO, Gossamer Bio

Gossamer was co-founded by Sheila and Faheem Hasnain. They were the dynamic duo that led Receptos until it was acquired by Celgene for $7.3 billion in 2015. They created value there with an oral drug for multiple sclerosis with a mechanism unlike other drugs on the market.

Building off that success made raising money a little easier this go-round. Gossamer received an initial shot of $100 million in venture capital so it could go out and assemble a pipeline of drug candidates. First came the money, THEN, hopefully, the comes the data.

Sheila is an MD by training, and grew up in a family where that was definitely the expectation. She had some crucial early career experiences at Genentech and BMS before she made it big as an executive at Receptos. From that set of experiences, you’ll hear how her philosophy of company building has emerged.

She’s not someone who seeks out a lot of publicity, at least as far as I can tell. She was a little shy at first about coming on the show. But I was glad she agreed. I think you will enjoy hearing her story.

Now, please join me and Sheila for The Long Run.

8
May
2019

Thank You, Biotech: Kili Climb to Fight Has Crushed Its $1m Goal for Cancer Research

Today, I want to say thank you.

Thank you to the biotech community for your Incredibly Generous support of the Kilimanjaro Climb to Fight Cancer.

You have enabled us to reach our goal of raising $1 million this year for lifesaving cancer research at Fred Hutch.

Who are we? We are a team of 28 biotech executives and investors. 14 men and 14 women. We’re from all over the country. Boston. San Francisco. San Diego. New York. Michigan. And of course, my hometown and Fred Hutch’s hometown, Seattle.

We are united by a passion for science, for the outdoors, for pushing ourselves physically and mentally, and by a desire to help others in need. In July, we will all meet in Tanzania to climb Kilimanjaro, the highest peak in Africa. It’s 19,340 feet above sea level.  

Thank you so, so much for supporting all of us.

This is the most exciting time ever for cancer research.

I can’t wait to see where the science takes us.

23
Apr
2019

Blazing a New Trail in Psychiatry & Women’s Health: Jeff Jonas on The Long Run

Today’s guest on The Long Run is Jeff Jonas.

Jeff is the CEO of Cambridge, Mass.-based Sage Therapeutics. The company made big news – front page of the New York Times  – a month ago. That’s when it won FDA clearance to sell the first drug ever for postpartum depression. It’s a big story for a number of reasons. Postpartum depression hits an estimated 10 percent of new moms every year in the US – about 400,000 people a year. The current SSRI drugs generally don’t work well, or work nearly fast enough in what can be an urgent mental health problem.

Jeff Jonas, CEO, Sage Therapeutics

Crucially, the Sage drug has a new mechanism of action – GABA receptor modulation. It’s not a reformulation or recycled incremental innovation. Not only is it new, this drug works. Brexanalone, marketed as Zulresso, works for about two-thirds of women with severe postpartum depression, who get it via infusion in the hospital after giving birth. The price: $34,000 for a course of therapy.

Sage now has given itself the task of cutting through the cultural taboos and stigma around postpartum depression. The biology is complicated. There’s a lot to learn. Disentangling it from environmental factors, and quantitative measurement of progress is hard – as with all psychiatric conditions. Postpartum depression is traditionally underreported and undertreated. This is supposed to be the happiest time in life, when a newborn arrives, right? Sage will succeed or fail as a commercial business based on its ability to roll the rock uphill, and encourage doctors and new moms to turn to this new molecule for help in getting through a difficult time.

Jonas, a psychiatrist by training who’s been around the block, knows the challenges in developing mental health drugs. In this conversation, he does a nice job of describing the landscape, and a few of the frustrations.

Now, please join me and Jeff Jonas on The Long Run.

18
Apr
2019

Life After Twitter

[Editor’s Note: David Shaywitz is a Palo Alto-based life science VC. He used to be active on Twitter. I asked him to share his reflections on leaving the platform–LT.]

Quitting carbs last year was hard. Quitting Twitter this year has proved delightfully easy.  You might even want to try it for yourself.

David Shaywitz

Twitter has tremendous upside. Most notably, it provides the chance to connect and engage with more, and more varied, people than you otherwise might, and in the process, learn things you didn’t know, and hear about interesting articles you might have missed. A real highlight of the medium was getting to know so many extraordinary people in the healthcare and biotech communities. My Tech Tonics podcast co-host Lisa Suennen (@VentureValkyrie) and I originally met on Twitter, for example.  I’m impressed by the ability of colleagues like Bruce Booth (@lifescivc) to use Twitter strategically and effectively, sharing thoughts on science and investing while steering clear of politics.  Many top scientists also enjoy the engagement of Twitter, as rock star Stanford chemist and Twitter newbie Carolyn Bertozzi (@CarolynBertozzi) recently highlighted on her captivating Long Run podcast with Luke (@ldtimmerman).

And yet.

As my economist friends (who, I acknowledge, I mostly met through Twitter) incessantly emphasize, everything is about trade-offs. The relevant question about Twitter isn’t whether there are benefits, but rather, whether the benefits are worth the costs. This analysis presumably will differ for each person.  For me, the calculus was pretty easy, and I’m hardly alone (indeed, “How I Improved My Life By Quitting Twitter” feels like a blogging subgenre at this point).

The costs of Twitter are consequent to the attention it demands and extracts, and the amount of mindshare you give over to it. Insidiously, it seemed to claim more and more of my time and emotional energy in the years since I first joined in 2011. You could say I became a very avid user. I tweeted around 45,000 times over an eight-year period, and had around 13,000 followers. Even though I carefully curated a group of just 40 accounts to follow, in effort to minimize distraction, it wasn’t working. By late February, I decided it was time to quit.

Thinking about this decision reminded me of something from my medical training. In residency, we were taught that “the longer you stay, the longer you stay,” meaning that the longer you stick around post-call trying to get everything tucked away, the more things are likely to come up and compel you to stay even later.  Similarly with Twitter, the more you engage, it seems, the deeper you are drawn in, and the more draining it can be.

Among the most destructive aspects of intensifying engagement with Twitter I noticed was the tendency towards the performative. As you increasingly share your experiences with your Twitter audience, sharing itself can become part of the actual experience.  An amusing sign, a beautiful sunrise, a travel indignity, an interesting paper — each might be shared, as the sharing becomes part of a single continuous act of experience.  It also contributes to the intimacy of the platform, providing, at its best, points of unexpected connectivity among engaged users as you discover others who might share your enthusiasm for an author, hobby, or beverage, or empathize with your distaste for a particular airline. 

Of course, the idea of performance permeates Twitter, as many if not most tweets feel like participants’ effort to publicly define themselves based on what they endorse or critique, based on who they endorse or critique, and based on the language or themes they use to do this, or their use of language demonstrating affinity with particular groups or ways of thinking.  Most obviously, this would include profile features such as “MAGA” on the right, or listing pronoun preference, on the left. But the signaling can also be more subtle, and it also seems nearly ubiquitous, to the point where at least for some users, most every tweet seems intended to announce or reify tribal affiliation.

In real life, I tend to focus on people first, with little regard for politics; while I probably shade towards the center-right, I’ve always had friends and colleagues across the political spectrum, and never thought all that much about either their politics, or mine.  Yet Twitter seems to transit in caricature, where so many participants become two-dimension versions of themselves – maybe because of how they present themselves, maybe because of how they are understood.  Participating on Twitter can feel like a constant battle to preserve dimensionality and nuance in a medium that seems determined to reduce it, and turn grey scale into black-and-white high contrast.  The medium rewards hyperbole and outrage, and seems to push everyone centrifugally towards the extremes. 

Fortunately, as Mona Charen recently noted, “Twitter Ain’t America.”  When you’re active on Twitter, you feel that most everyone in the world is on it. But this turns out to reflect a hefty degree of ascertainment bias, as users are constantly reminded of those who participate, and lose sight of the many more who largely avoid the platform — including the vast majority of senior executives I encounter.   In 2012, I argued that most CEOs didn’t need to be on Twitter; I suspect most now agree, leading many to maintain de minimis accounts largely managed by their PR departments, and utilized almost exclusively for broadcast, rather than more substantive engagement.

Immediately after I quit Twitter, I discovered a book that tremendously fortified my decision: Deep Work, by Cal Newport.  The basic thesis is that concentrating on difficult problems is hard, and requires practice; instead, we tend to avoid such “deep work” by engaging in a range of fairly superficial activities. His argument is that we would do well to deprioritize these in favor of learning how to focus.

In addition to being entirely off Twitter since February, and deleting it from all my devices (I’ve retained my account as I can envision having it managed dispassionately by a PR firm at some point simply to share articles or perspectives), I’ve also deleted both LinkedIn and Apple News from my iPhone. The LinkedIn notifications were increasingly distracting (with over 900 pending invitations, signal is increasingly difficult to detect through the noise, and I’m increasingly tempted to drop this platform as well), and Apple News always felt like a rabbit hole.  I never was a Facebook user, which saved me the trouble of quitting. 

Among the surprises I’ve encountered is that the moment-to-moment news flow is far less critical than it can seem when you’re on Twitter.  Almost nothing is all that urgent. Reading a news digest daily seems to be enough for me to stay up with current events. Once a week, or even less, would probably be fine for most things.  Perhaps it’s the “slow news” analog of slow food, and it seems to work really nicely, and it feels wise not to confuse the heat of agitation with the light of insight.

While I’m not sure I’ve yet achieved the “Deep Work” ideal, I feel that I am progressively rediscovering my ability to focus intensively, and am truly enjoying the opportunity to dive deeply into tremendously exciting areas like immuno-oncology and gene and cell therapy.  Admittedly, it probably helps that I love what I do, and I’m blessed to be in an environment that provides access to the tools I need, and in a role that affords constant opportunities to engage, in person, with so many creative and highly-motivated scientists, physicians, and entrepreneurs.

Outside of work-related reading, I’ve also enjoyed several unusually good books, including in particular: Dreamland, by journalist Sam Quinones (a superb, highly nuanced account of the opioid crisis); The Compatibility Gene, by immunologist Daniel Davis (I had recently reviewed his latest effort; The Beautiful Cure, for the Wall Street Journal, and was delighted to discover how much I also enjoyed his earlier book about the MHC); and The Secret Life of the American Musical (a guilty pleasure), by Broadway producer Jack Viertel.

While there are aspects of Twitter I miss, the benefits of restoring mindshare and attention far outweigh anything I’ve left behind.  One of my most precious resources is my attention, and I’ve recognized the importance of nurturing my ability to focus, and defending against distraction, while somehow still remaining open and receptive to exciting and orthogonal ideas.  I don’t think there’s a formula for achieving the ideal balance, but quitting Twitter has felt like a great place to start.

9
Apr
2019

The Road Less Traveled in Glycoscience: Carolyn Bertozzi on The Long Run

Today’s guest on The Long Run is Carolyn Bertozzi.

She is a professor of chemistry at Stanford University, and an entrepreneur.

Carolyn Bertozzi, professor of chemistry, Stanford University

Her research is focused on glycans – the beautiful and bewilderingly complicated sugar molecule structures attached to proteins. These carbohydrates are often underappreciated by biologists, and “orthogonal” to the way many think. But glycans are known to play a significant role in how proteins behave, and a wide variety of interactions between cells.

Whether you can aim drugs at some of these glycan targets and get the disease modifying effects that a typical medicinal chemist desires – that’s the kind of open question that has driven much of Bertozzi’s research over the years.

Bertozzi took a gamble early in her career to get here. She joined an immunology lab where it wasn’t entirely obvious that a chemist would add much. By forcing herself to think outside one discipline, she ended up bridging fields in an interesting way. The raw and messy edges of disciplines is often where big advances occur.

Without question, Bertozzi is now an established star. She won a MacArthur “genius” grant early in her career, later won the prestigious Lemelson-MIT Prize for invention, and was elected by peers into the National Academy of Sciences. She’s known for leading teams that developed tools to provide better imagery, better information, about glycan behavior in live action. When you develop tools or methods that lots of people can use and which advance an entire field – that’s the kind of thing that gets you placed in the scientific history books.

Bertozzi is also a warm and funny person to talk with. She cares about open science to speed innovation, communicating science to the wider world, and in supporting women’s advancement. I enjoyed asking her about how she got to this point in her career, and how she thinks about biology evolving to embrace the kind of complexity that once deterred people from getting serious about her chosen field.

Please sit back, relax, and join me and Carolyn Bertozzi on The Long Run.

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