Cancer Survivor and Cancer Drug Developer: Laura Shawver on The Long Run

Today’s guest on The Long Run is Laura Shawver.

Laura is the CEO of San Diego-based Synthorx. This company, based on research from The Scripps Research Institute, is using a couple of newly invented base pairs of DNA to make site-specific modifications on fully expressed proteins. This capability, Synthorx believes, could be put to practical use to craft ideal drug-like properties into recombinant proteins. The drug itself will be a protein that doesn’t exist in nature, with a unnatural amino acid that serves as a hook that pegylation molecules can attach to, which improve the half-life and dosing schedules for IL-2.

Laura Shawver, CEO, Synthorx

Pretty cool, huh?

Science nerds, you were hooked by the new base pairs of DNA, right? For the more medically minded, the potential applications are big. Synthorx has created a modified version of Interleukin-2, the inflammatory cytokine. It’s been around for a couple decades. It’s known to cure a small percentage of patients with metastatic melanoma, but also to cause massive toxic side effects. Synthorx, along with a few others, including San Francisco-based Nektar Therapeutics, have been working on re-engineered versions of IL-2 that seek to exploit new understanding of the way the drug works, in order to dial up the tumor-killing capacity, while dialing down the toxic side effects.

If this works, it could open up a world of possibilities for IL-2 to be combined, more safely, with other cancer immunotherapy drugs with complementary mechanisms of action. First things first, Synthorx has to get its first clinical trial up and running in coming months and gather the first glimmers of data to test its hypothesis. It has a long road ahead.

Laura knows the drill. She’s a veteran entrepreneur who has been through a few up and down cycles. She’s a native of Davenport, Iowa, got her scientific training at the University of Iowa, and has been a part of West Coast biotech teams at Sugen (now part of Pfizer), Phenomix, Cleave Biosciences, and now Synthorx.

Along the way, she was diagnosed with ovarian cancer. She not only beat that diagnosis, she founded a nonprofit foundation, the Clearity Foundation. For the past decade, it has leveraged her biotech know-how and network to help other women. I found that part pretty inspiring.

Now, please join me and Laura Shawver on The Long Run.


Who Will Be the Next Celgene of Dealmaking?

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 the full article 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, Sept. 11-12 in Boston. REGISTER HERE



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.


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.


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.


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.


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.