Under the Radar: Raindrops on Roses

Time to appreciate some of the incremental advances and ideas that together will usher in the age of personalized medicine. Favorite thing by favorite thing — that’s how the world changes. So move over Julie Andrews.

Research-wise, a major favorite thing is seeing a real step in making gene therapy actually work – a decades-long dream for many of us. Looks like British scientists have had preliminary success in treating Hemophilia B by injecting patients with the correct form of a defective gene. This is exciting news (in time for the holidays!) for those suffering from hemophilia. It has good implications, too, for those living with and working on diseases that have not-so-good histories with gene therapy. 

Very nice to contemplate, too, is a new venture involving Stanford’s Atul Butte, MD, PhD. I’ve mentioned Atul before, but just because he’s a friend doesn’t mean he’s not a star — he’s been pioneering the development of scientific tools that leverage genetic data to improve clinical care for years. He and a dream team — Russ Altman, MD, PhD; Euan Ashley, MD, PhD; Michael Snyder, PhD; and John West — have started a cool new company, Personalis, dedicated to bridging the gap between personal genetics and clinical medicine.

In terms of company ideas, again, I’m going with the importance of the incremental, and the importance of providing value to customers and financial success to investors. The back–to-basics approach that companies like Enzymatics, Cell Signaling and abpro are offering is refreshing. Watch for companies that can bootstrap, or that can subsist on only "angel round" investment without heavy infusions of cash to make it. A template for great start-ups? New England Biolabs. It started decades ago, and is still going strong.

Playing to your strengths is key, and the McKernan family is excellent at identifying and building value. Keep your eye on Courtagen Life Science, where father and sons Richard, Brian, and Brendan McKernan are Managing Partners and Board Members (Richard is Chair). The current team built Agencourt, and bought part of Genome Therapeutics. They also identified George Church's polony technology (key for next gen sequencing) and parleyed that into a value-added sale to Applied Biosystems and Beckman Agencourt. So far, they have developed protein immunoassays for point-of-care diagnostic and contract research markets, and they recently launched a biomarker discovery effort. Knowing them, they have plenty of plans for the future.

And then there are the unsung heroes.

Kudos to Morten Winger (and John Lindsay) for discovering and developing the value in Halo Genomics. They built value with their next gen sequencing sample preparation product, stayed under the radar, and sold quickly to Agilent. I have lots of faith in Mike Irwin, Director of Genomics, Americas Field Operations at Agilent and his team’s ability to capitalize on that new line. By the way, Morton and John did the same thing with ProXeon, which sold to Thermo. Can't wait to see their next act.

Another win for Mike Lucero, the father of Real Time PCR marketing. He’s succeeded at TaqMan, then at Fluidigm (went public this year) then at QuantaLife (sold to Bio-Rad). It’s been a brilliant run that even includes a break to lead Stokes Biosciences (which in April was stealthily sold to Life Tech). What will Mike do next?

Ruth Kaucher is one to watch. After a great career at Applied Biosystems, she moved to Beckman Coulter Genomics to build their genomics services group. But it just got more interesting. She is now VP of NA sales for BGI, a Broad-Institute-like Asian not-for-profit to which many big conservative pharm companies are already outsourcing their sequencing. BGI gave an impressive presentation at ASHG about focusing a worldwide effort to identify gastric cancer genes for the Cancer Genome project. We have all heard the China “sleeping giant” story; now it will be fascinating to see if BGI moves into a genomics scientific leadership role worldwide.

My last personal favorite for the day is woman-with-a-mission Linda Avey. After co-founding 23andMe then setting up a very powerful Alzheimer's consortium at BU with Bob Green, she is now the CEO of Curious, Inc. Aren't you?

If that’s not a list that beats whiskers on kittens, I don’t know what is.

Steve Jobs, Innovator

The legacy of Steve Jobs is breathtaking. In many ways, he remade our expectations and experience of technology. In many ways, that is, he remade our path to the future. As researchers, scientists, and entrepreneurs who dedicate our lives and careers to innovating in our own fields, I think we have a special appreciation for this remarkable man and his accomplishments. And we have a special opportunity, perhaps even an obligation, to learn from the aspects of his character that allowed him to achieve what he did. It feels like a fitting tribute to do exactly that.

Among Jobs’ iconic traits — along with brilliance, vision, an incredible appetite for risk-taking, and a passion for success — was what I call intellectual adventurousness. Carmine Gallo digs into this beautifully in The Innovation Secrets of Steve Jobs: Insanely Different Principles for Breakthrough Success. Gallo describes Jobs as having "spent a lifetime exploring new and unrelated things” and argues that this was a major contributor to his inventiveness.
That this interest in seemingly disparate ideas — and of course, the ability to bring them together — was key to Jobs’ abilities as an innovator aligns closely with my experience with some of the most interesting and successful entrepreneurs in the life sciences.

In our field, the intellectual adventurers are the innovators who’ve pushed through the boundaries of the serial-science paradigm of life-science research. They’ve redefined life sciences as interrelationships and systems — it’s a perspective that allows for solving problems on a much bigger scale. These life science innovators pull ideas from biology, of course, but also from high technology, physics, math, and engineering. This “Think Different” mindset has allowed them to originate, recognize, and act on new ideas.

One of the most successful “Jobsian” thought-leaders in life sciences is Jay Flatley. He was a major force in the genomic-tool revolution and has consistently stayed at the forefront. Jay is CEO of Illumina, a company founded in 1998 and with a market cap of ~$5B. Jay has several traits reminiscent of Jobs. He has the same "out-innovate-all-competitors" attitude. And of course, a passion for technology: he’s frequently seen presenting his personal human genome sequence on, naturally, an iPad2. It’s a demo that comes complete with annotated personalized information and a great screensaver shot of his wife.  Significantly, the similarities also include an orthogonal background. Jay has a BS in Economics from Claremont McKenna and an MS in industrial engineering from Stanford. It’s a grounding that lets him see both science and business opportunities others might miss, such as acquiring Solexa and investing in Oxford Nanopore.

An innovator-hero with an even longer history of new ideas and Jobs-like breadth of intellect is Leroy Hood, MD, PhD. Not only has he led in the fields of automated genome sequencing, microfluidics, systems biology, and personalized medicine — he created those fields in the first place. Along the way, he’s co-founded at least 13 companies, including Amgen, Applied Biosystems, and Rosetta Inpharmatics. That might be enough for most of us, but Lee Hood, 72 this month, is still pushing, still inventing, still shaping the future. Even while running his Institute of Systems Biology, he launched Integrated Diagnostics, which is creating blood-based diagnostic tools for the early detection of cancer. There’s a satisfying symmetry to his having led the development of molecular tools decades ago, and his now deploying those tools against devastating diseases such as lung cancer today. It all seems to fall under his ultimate ambition: to usher in a genetic-based era of what he’s named “P4 medicine” —medicine that is predictive, preventive, personalized, and participatory. 

A younger innovator in the Steve Jobs tradition of intellectual adventurousness is tenured Stanford professor AtulButte, MD, PhD.  In 2002, I had the pleasure of working with Atul at Flagship to launch Selventa (then Genstruct). Back then, he was completing his PhD at MIT/Harvard and, already a board-certified pediatric endocrinologist, he was running the Computational Biology Group at Children's Hospital. Atul has a wonderful, multifaceted perspective grounded in his background as a physician, scientist, and software engineer. Fittingly enough for this reflection about Steve Jobs, Atul’s software engineering resume includes several stints at Apple. Who knows? Maybe Jobs was a direct influence … In any case, Atul’s career has encompassed seemingly divergent disciplines, and the result, as with Jobs, he has inspired ideas. In the past year, he has launched two separate new companies, Personalis and Numedii, that use genomic data to drive pharma pipeline development and clinical success. As with the idea of using Tagamet for lung cancer, Atul continues to be a source of the unexpected.

Steve Jobs said he “wanted to put a ding in the universe.” Obviously, he did, and it’s an honor to be in a field that allows us to strive to do the same. So thank you, Steve Jobs. And I think your own words speak for all of us today:  Insanely great.

Good Things Come to Those Who Bait

Even if you’ve never pulled on a pair of waders, you know that to hook the right fish you need the right lure. Why do so many people forget this when angling for jobs?  It’s all about specificity. About what sets off your strengths to make it obvious you’re particularly perfect for a particular job.

Think metrics. After many years of placing high-level commercialization people, I still puzzle over why business leaders who live and die by sales and revenue numbers so often leave metrics off their resumes.  In my experience, there is a direct correlation between your showing good metrics, and my clients’ being interested in speaking with you.  Whenever possible, bait your line with numbers: sales numbers, product line revenues, quota achievements. You will get many more call backs.

Tell and show. One of my candidates, a successful marketing director in the medical device field, took his excellent resume one step further by creating a professional-quality website to market himself. The site gave employers a full portfolio of the candidate’s white papers, marketing brochures, and PR pieces. Perhaps as important, however, the site showcased those materials in a way that demonstrated my candidate’s marketing skill – and thus his suitability for the position he sought.  Employers were able give him a virtual test drive. By the way, he got the interview and the offer.

Consider graphics, but stint on the stunts. I have seen a few rainbow-colored resumes in my time, and a few wild fonts, as well. Need I mention that I’m not a fan? There is, however, a place for different kinds of resumes that include thoughtful, well-executed visual information. One mechanical engineer I placed illustrated his resume with CAD designs of next gen sequencers and robotic equipment, and captioned the visuals with just the right amount of descriptive text. This inventive resume allowed employers to see in a glance what the candidate had designed and built, and allowed them to judge for themselves  the candidate’s experience with microfluidics, optics, etc.  Since I’ve placed this engineer in two jobs in eight years, we can safely conclude that resume works.

Next Gen Sequencing Comes Into Its Own – Big Time.

There’s an undeniable excitement when a new technology really hits its stride, and that excitement pretty much sparkled all over John Boyce's third Consumer Genetics Show. There was the A-list of academic and corporate speakers. There was the participation of the full range of stakeholders, from regulatory experts, genomics CEOs, and academic leaders to cancer patients (the affordable $20 entrance fee helped). There was the fact that John is one of the most well-networked people in our business, and he’s got a Midas touch when it comes to anticipating markets and opportunities. Bonus points for the “old home week” feel for former ABI-ers like me. Above all, though, there was the – no other word for it – thrill of witnessing a technology reach wow level. That makes for one heck of a conference.

One huge conference headline is that people are finally making real money off NGS. Jonathan Rothberg was radiant throughout  his presentation. Wouldn’t you be, if you’d sold Ion Torrent to LifeTech for $350-725M (depending on milestone payments)? He dazzled the audience with the story of Ion Torrent’s sequencing the deadly E. coli outbreak in Germany – in two hours. Jay Flatley was justifiably jubilant, too. He’s grown Illumina's market cap from $4B to $9B, and done it in a single year. Outstanding financial returns – and with the MiSeq platform about to be launched this summer, it looks like the rest of 2011 will be bountiful for Illumina shareholders too. Jay continued where he left off last year by loading his entire genome on an iPad 2; then extended the show-and-tell to include a look at the annotations and software for personal genome analysis. He also announced a dramatic drop in whole-genome sequencing prices to only $7,500 for an individual or $10,000 for a tumor and a patient. Incredible.  

This NGS market will drive a great deal of opportunity. George Church, our resident Harvard expert, predicted that very soon there will be hand-held NGS devices with no PCR or special sample prep, and that in-situ 3D/4D NGS for cancer and infectious diseases will be emerging. He predicted, too, that we are hitting the data deluge, which means advances in interpretation and integration software will take center stage. That's good news for Ingenuity, Selventa, GeneGo, DNA Nexus, and lots of those bioinformatics companies poised for just this opportunity. Paul Morrison, our Dana Farber Cancer Institute NGS guru, led a lively panel discussion that included some of the powerhouses in NGS platforms. Illumina was there, as were new entrants such as NobleGen, NabSys, and GnuBio. They’re all hoping to “pull a Rothberg" – and let's hope they can.

What’s really becoming clear is that the power of Next Gen Sequencing and other developments could help shift the traditional balance between the drug industry and its poor stepchild, the diagnostic industry. Randy Scott, CEO of Genomics Health, made the point that oncology drugs are effective in only about 20% of patients. That means that we are usually not providing the correct treatment for patients, and are therefore needlessly over-prescribing chemotherapy when another approach would be better. No wonder, then, that Randy joined Steve Burrill and a chorus of others in calling for a strong independent diagnostic industry not subservient to the pharma industry. Amen.

In closing, let's all hope that our drug costs go down and our access to highly informative personalized diagnostics tests go up. And let's also hope that John Boyce, now CEO of GnuBIO, a new entry in the Next Gen sequencing space, is eating his Wheaties and will still have time to organize a great fourth conference June 2012. Kudos again to you John.

Boston's answer to the JP Morgan Life Sciences Conference

Once again, the Massachusetts Technology Transfer Center scored a direct hit with their Early-Stage Life Sciences Conference VII. Partnering with the Merck Research Labs, they lined up an impressive array of new companies loaded with pedigreed, serial entrepreneurs from Harvard, MIT, Genzyme, Hologics, and other leading academic centers and corporations. Each of the sixteen companies had ten minutes to pitch their newco to investors and the biotech community – which gave the proceedings a kind of mini- JP Morgan Life Sciences Conference feel. Presenters ranged from medical device, Rx, and Dx companies to tools players. 

Donna Ambrosino kicked things off as the keynote speaker and conveyed some riveting examples of MassBiologic ’s successes, including the stellar story of developing an antibody Rx for SARS in only 31 months. There were several platform companies that caught my eye, including NobleGen Biosciences, a single-molecule DNA-sequencing company that has developed an optical nanopore sequencing approach. It looks to give Pacific Biosciences a run for their money and has the speed to sequence an entire genome in one hour, something we never dreamed about during my days at Celera. The winners of the MIT $50K Entrepreneurship Competition in 2005 presented Pharyx, a novel microfluidic bioreactor platform; and Alexey Wolfson introduced us to an exciting gene knockout RNAi company, Advirna, that could be a great acquisition target for Thermo Fisher, Life Technologies, or others. Optasia Medical and Translational Sciences presented some exciting new solutions to interpret and analyze CT and PET imaging.

In terms of new medical device companies, one of my Flagship Ventures colleagues, Jay Schwartz, presented Acuity Bio, an exciting drug delivery company with a polymer implant for treating non-small cell lung cancer. He also discussed potentially lucrative secondary markets, including colon and breast cancer. As we all know, crossing the blood/ brain barrier is not easy, but Al Kyle showcased Perfusion Technology, which utilizes ultrasound as a non-invasive method for drug delivery to the brain. There was also a new ablative therapy company, Thermedical, that will be able to offer revolutionary treatments for ventricular tachycardia and liver cancer. And then there was eye-opening (sorry!) idea of medication via contact lenses. Dr. Joseph B. Ciolino from Mass Eye & Ear is working with the famous drug delivery wizard Bob Langer to develop a contact lens that can deliver medicine in a time-release fashion to treat glaucoma.

Okay, now for the drugs... On the therapeutic side, two oncology companies presented: Bryan Oncor and OncoPep. OncoPep, developed at Dana Farber, is launching a new line of cancer vaccines to combat a broad spectrum of cancers. Bryan Oncor’s drug is based on a somatostatin peptide and has an imaging diagnostic paired with their Rx for lung cancer. Basically, they run a peptide imaging diagnostic on potential patients. If their cells light up positive for the somatostatin receptor, they are a match for the therapy. A very exciting combo – that yes, illustrates the promise of personalized medicine that I wrote about in an earlier post.

Continuing on with protein-oriented drugs, does the thought of oral antibody therapies seem farfetched? If so, it won’t for long. Avaxia Biologics has developed an oral antibody therapy to combat inflammatory bowel disease, attacking a $3.5B market.

One fun health-techy company that presented was Segterra. It is a web-base personalized path to health, wellness, and performance. They analyze a sample of your blood, and in conjunction with your individual goals for health or athletic achievement, provide the diet, nutrition, and exercise plan best for your signature biochemistry. Looks promising, though I’ll admit that it gives me some pangs of guilt about gobbling down that hot dog for dinner. On the other hand, skipping my morning run to attend the conference was totally worth it!

The personalized medicine market heats up

One of the markets that’s got the industry most excited lately is personalized medicine – the use of detailed diagnostics to determine individualized medical treatments. Little wonder that the approach is garnering attention, as the number of stakeholders seeing new ways to benefit seems to grow daily. Think platform tool providers, whose imaging and genetic tests are going to be relied on in completely new ways. Think pharma companies, who’ll be able to increase their shot at getting drugs through clinical trials by weeding out non-responders in advance. And of course, think hospitals and physicians, who’ll be able to pinpoint treatments that will get patients better sooner and decrease toxicity and other negative side effects. 

Cardiovascular disease is good example of personalized medicine in full swing. In the past, a cardiovascular patient’s newly-prescribed blood thinner often became a mini science experiment. Too high a dosage could mean hemorrhage; too low a dosage, and clots could land patients them back in the OR. Today, a quick (genetic) blood test determines optimal dose and is radically reducing hospitalization rates.  

But where more and more industry people are really expecting to find pay dirt is with the application of this kind of customization to an intractable problem like breast cancer.
We’re thankfully already past the time when the disease was identified and treated almost exclusively according to its tissue of origin – a crude categorization, as breast cancers are not all the same – but we’re far from where personalized medicine will be taking us soon. Today, genetic testing allows several cancers to be typed and paired with individualized therapy, and the area is expanding fast. 

Genomic Health, Agendia and Myriad have diagnostic tests that can help pair patients with the most effective treatment regime, in effect personalizing their treatments. Multi-gene tests, such as Agendia’s MammaPrint™, include more genetic information, and are advancing the field. And that’s just the beginning. 

A guy to watch in personalized medicine is Raju Kucherlapati, Ph.D., Professor of Genetics at Harvard Medical School.  He is definitely a key thought leader driving this field forward, and he’s a truly lovely person, to boot. He also organizes a great, not-to-be-missed conference through Harvard and Partners every November. 

We expect to be placing more and more leaders and researchers in personalized-medicine-related fields this year. Kind of nice when a big new idea promises a healthy future for us all medically – and financially, too!

Where will tomorrow's leaders emerge?

I know, I know – you’re busy and your budget is tight. All the more reason to help young scientists and entrepreneurs advance. Student internships are an excellent way to add additional horsepower to a tactical project while helping train our next "best and brightest." At Flagship Ventures, I engaged a number of the MIT Harvard e-Lab graduate students. They did an excellent job developing competitive landscapes, researching markets and conducting due diligence on new companies and opportunities we were considering. Many of the [executives in my network] and I have found that hiring summer lab interns can help defray the workload pinch when full timers go on vacation. And what a great way for a student to learn how sequence DNA or write a business plan!

This year the Mass Life Science Center has announced a renewal of their internship program. Last year’s program received almost 900 applications and placed 170 interns at 94 companies throughout Massachusetts. If you are a student of a Massachusetts college or university, or are a Massachusetts resident attending an out-of-state college or university, consider applying to this great program. If you are a company, consider helping to train the next generation of leaders. Who knows? That summer intern may become a valuable full time addition to your company.

Spring is in the air and — cautiously — so are IPOs and buyouts.

Venture capital and investment funding continue to be tight for emerging companies, but the first glimmers of hope are out there – really BG Medicine, which I had the pleasure to help found, successfully launched their IPO on NASDAQ in February. Granted, they didn’t raise as much as they’d hoped in 2008; but they now have the capital to continue their biomarker/cardiovascular plans. February also saw about $75 million raised by Fluidigm, an emerging leader in microfluidics and genomics. After spending their first few years developing a protein crystallization platform, Fluidigm has wisely moved into the larger RT-PCR genomics market and are peripherally selling into the Next Gen Sequencing area.  

Next Gen Sequencing itself has been surrounded by doldrum-defying activity for a while now, and the continuation of this trend adds to the promise of a springtime economic thaw. It started in with Life Technologies spectacular acquisition of Ion Torrents. Will they hit all their milestone payments to earn the $750M?  I'd put my money on Jonathan Rothberg any day and so far it looks good. Complete Genomics, a Next Gen Sequencing service provider, contributed to the buzz by successfully raising $54M in an IPO in November.

On the diagnostics side of things, Quest Diagnostics is in buying mode and just purchased Athena Diagnostics, a small diagnostics service, for $740 million in cash. It’s a move that will help make Quest a leader in neurological disorder testing. They’ve also announced they’re buying Celera Corporation for $671 million.

It’s beginning to look like these events are part of a fresh start: an upswing in investments and in exit strategies for new companies with solid technologies and market opportunities.  Here’s to spring!

Upcoming conferences – get there!

Spring offers a great crop of life science meetings in the Boston area, and you still have time to sign up.

March 21-22: The Massachusetts Biotechnology Council's Annual Meeting is focusing on personalized medicine. There will be exciting presentations and panels on an array of subjects, but I hear the gene patents panel will be of particular interest.

March 23:  The LRIG New England Chapter is hosting an event at AstraZeneca. Ion Torrents, part of Life Technologies, will be presenting their NextGen Sequencing platform. IonTorrents was started by the serial entrepreneur Jonathan Rothberg, who founded 454 Sequencing, CuraGen (now part of Celldex), and RainDance Technologies. 

April 14:  The Massachusetts Technology Transfer Center sponsors a great NewCo opportunity for investors and entrepreneurs to see or show new companies in the pipeline. Billed as the Early-Stage Life Sciences Technology Conference VII, this is an annual event held at The Merck Research Labs to showcase companies with platform technologies developed at the research institutions, hospitals and universities. 

June 7-9: Consumer Genetics Conference.  John Boyce has done an amazing job capturing the consumer genetics landscape in this two-day meeting. He attracts top science and business people in the field; past presenters have been Francis Collins (NIH), George Church (Harvard), Jay Flatley (Illumina) and Greg Lucier (LifeTech).  

June 2:  Massachusetts Life Sciences Innovation Day is one of my favorite one-day conferences because of the breadth of platform, medical device, and pharma presentations. Past presenters have included George Whitesides from Harvard, Matthew W. Emmens from Vertex, Mara Aspinall from On-Q-ity, and James J. Mongan, President/CEO of Partners Healthcare.