Tag Archives: CBT Advisors

“Alternatives to VC” panel video (actually very much about VC, especially in Europe) – BioEurope Spring, March 2013

This is not a traditional post but rather a link to a video of a fun panel that I moderated at BioEurope Spring in Barcelona in March, 2013. The discussion touched on several hot issues in funding innovation in life sciences, especially translational research.

Here’s the link:
http://www.partnering360.com/insight/showroom/id/0_p9ec32p3

To help you find points of interest, I’m listing some approximate time stamps below.

PANEL DATE: March 11, 2013

PANEL DESCRIPTION

With the shortage of classical VC investing and the ongoing boom in early opportunities and strong entrepreneurs, traditional VC is beginning to share the spotlight with alternative models. For therapeutics companies that have already raised some capital or especially those that have products in the clinic, there are some new alternatives to choose from, including option deals, one-product financings from VCs, and pre-IPO royalty-based financing.

Moderator:
Steve Dickman – CEO, CBT Advisors

Panelists:

  • Sinclair Dunlop – Managing Partner, Rock Spring Ventures
  • Joël Jean-Mairet – General Partner, Ysios Capital
  • Kevin Johnson – Partner, Index Ventures
  • Melissa Stevens – Deputy Executive Director, FasterCures

CONTENTS

  • 0:00 Panel intro (Steve Dickman)
  • 3:19 FasterCures (Melissa Stevens), channeling non-dilutive foundation cash into therapy development
  • 4:29 Index Ventures (Kevin Johnson) intro and description of pharma-backed fund
  • 4:50 Rock Spring (Sinclair Dunlop) intro – UK VC
  • 5:20 Ysios (Joel Jean-Mairet) intro – Spanish-European VC
  • 7:25 What are the mechanics of asset-based financings? We’ve done 27 of them… (Johnson)
  • 12:15 Ysios (Jean-Mairet) view on asset-based financing “experiment” in molecular diagnostics
  • 14:00 Why Index would love to invest in diagnostics but can’t do it (Johnson)
  • 18:30 How things are better in lean, asset-based companies (Johnson) “Working in a tinpot biotech is more fun” than in an old-fashioned fully integrated company.
  • 19:55 How Rock Spring (Dunlop) does early-stage platforms & products
  • 21:15 Refinancing risk has grown (Jean-Mairet)
  • 22:45 How times have changed in LS VC (Jean-Mairet)
  • 24:15 The key to avoiding “zombie” companies – suicide (Johnson)
  • 25:40 More (interesting!) details on FasterCures and how foundations are changing the investing game (Stevens)
  • 28:48 National MS Society’s “Fast Forward” venture-like group (Stevens)
  • 30:55 CF Foundation and its Vertex and now Pfizer relationships (Stevens)
  • 32:55 American Heart Association (AHA) learning more about venture philanthropy (Stevens)
  • 36:15 Venture philanthropy in Europe (Dunlop)
  • 46:15 Tech transfer report card (Dickman, panel)
  • 57:00 How European & Israeli seed funds are trying to bridge the venture gap (panel)
  • 1:04:00 How to ensure succession in biotech (Johnson, panel)
  • 1:08:00 Why there are not more young entrepreneurs in life sciences (Johnson)
  • 1:15:00 The Andrew Lo “Megafund”: will it fly (Stevens, panel)
  • 1:18:00 Other debt models for supporting translational work (Jean-Mairet)
  • 1:22:00 Cross-border seed-stage investing (Dickman)

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Can the Amgen Takeout of Micromet Juice German Biotech? Can Anything?

By Steve Dickman, CEO, CBT Advisors

Now that Germany has had its first billion-dollar biotech exit, it seems it would be about time for the beleaguered German biotech sector to enjoy a welcome jolt of juice. Amgen plans to lay out $1.16 billion in cash to acquire Micromet (NASDAQ: MITI) in a deal announced on January 26.

Generally, big exits create new opportunities. As a wishful example, consider the impact of the upcoming monster $10 billion IPO of Facebook, which will likely spark financially secure engineers to start new companies and multimillionaire founders to start new venture funds.

So is it time to celebrate in Germany? Not exactly. But there may be some good news for German biotech if we dig deep enough. I believe that the Micromet acquisition and other recent successes could serve as a valuable proof-of-concept for biotech products and technologies “made in Germany.” There are plenty of seedlings growing up from German universities and spinning out of existing companies. This is a good time to focus on them.

Tough trickle-down

Amgen’s big-ticket acquisition will likely not translate directly into a rash of new startups. The techniques used in inventing Micromet’s products – bispecific antibodies for systemic treatment of cancer and other severe diseases – are not easily transferred. Amgen has said that it intends to retain virtually all two hundred employees located at the Munich site. Some itchy would-be founders may eventually leave but the short-term impact will be limited.

More difficult for the German biotech scene, Micromet has not been a purely or even mostly German company for a long time. Its January, 2006, reverse merger with the failed California biotech CancerVax gave it a NASDAQ ticker symbol and a U.S. headquarters. The company raised $328 million in total of which $264 million came in PIPEs and follow-ons following the CancerVax merger. There was also approximately $60 million cash on hand at CancerVax when the companies merged.

Despite its impressive size, the Micromet exit is surprisingly no more than “a mediocre hurrah” for local VCs, one Germany-based VC investor told me. “VCs here have mixed feelings about this deal since … very few investors [who made initial investments into the company] were able to make money.”

Dollars slipping away

Why not? Clinical trials were going to be expensive. Likely acquirers were far away. Some funds faced restrictions on cross-border or public investing. Others simply did not have the money to push a company so far towards clinical proof-of-concept. The lack of local capital threatened to leave the company unable to prove the value in its innovative products. Hence, many of the gains were made by investors in public shares such as crossover funds and hedge funds.

Before I unveil my modest proposal for how to help the next crop of projects and companies in Germany, let’s look at where we are, how we got here and then I’ll return to where we can go next.

Bye-bye bubble

The world’s biotech boom of the late 1990s and early 2000s proved to be too much of a bubble for many German companies and investors. Some early companies were not built for sustainability and after some 2000-era fairy-tale financings on Frankfurt’s Neuer Markt, public biotech investors in Germany were badly burned. They have largely not returned.

The situation is not much better for venture capital funds. Otello Stampacchia, managing partner at Omega Funds, one of the institutional investors with the longest-term stake in Micromet, said that the VC shortage afflicting Europe is “particularly bad in Germany. Compared to what has happened, say, in the UK, there has been a colossal shrinkage.”

What is left in Munich, Berlin, Stuttgart, Heidelberg and other fertile biotech regions is both promising and problematic: truly world-class science; experienced entrepreneurs and employees; over eight hundred companies; and a severe lack of both venture and growth capital. Hence, in Micromet’s case, the truly creative solution of a reverse merger in 2006 and the successive financings in 2006, 2008, 2009 and 2010.

MITIgating factors

The company’s big exit, albeit on a leukemia product not yet been approved by FDA, is a beacon of light for German startups. I asked eight venture and public investors in Germany about the acquisition’s impact and the response was one of optimism tempered with caution. “The general message is positive, namely, that German biotech is capable of turning cutting-edge basic research into a full-blown company,” said one financial VC in Munich.

The capital shortage that Micromet encountered in Germany is emblematic of issues faced everywhere by therapeutics startups: the more innovative you are, the tougher it is. It takes more time than a VC fund lifetime of ten years for such technologies to reach Phase 3 or commercial status or achieve a big exit. A typical timeline is fifteen years. (Micromet was founded in 1996.)

Micromet rings the bell

Micromet rings the bell

Now that Micromet has proven the case for innovative biotech products nurtured in Germany, the burning question for investors, one of them told me, is “whether deals like the Micromet M&A creates more international VC activity in Germany.” With IPO markets shuttered and little in the way of growth capital, I suspect that the answer is likely “not anytime soon.”

But even if traditional VC does not return in significant amounts to Germany, some of the near-ripe fruit there is worth watching. Those companies include two that had the honor of presenting at the 2012 JP Morgan Healthcare Conference: NOXXON, based in Berlin, which is carrying out multiple clinical trials in a variety of high-value indications for its exciting spiegelmer technology; and Probiodrug, based in Halle, which is pursuing a unique and highly interesting approach to treating Alzheimer’s disease by attacking the underlying disease biology in a novel way. A third company, Curetis in Stuttgart, announced in November that Roche Venture Fund had made an investment alongside a Netherlands-based financial VC fund, Forbion. Curetis’ technology can rapidly identify pathogens causing hospital-acquired or severe community-acquired infections like pneumonia by bringing highly multiplexed PCR reactions into the hospital lab.

Those are just the most advanced companies. There are many more behind them and their technologies and approaches have much to offer. (Affimed in Heidelberg and Synimmune in Tübingen are just two examples in the bispecific antibody space.) Consider the technology areas in which German companies have thrived: they are mostly intricate (like Micromet’s bispecific antibody technology or Curetis’ 50-analyte PCR); they are more likely to be enabling technologies than therapeutic products (one local expert estimated that only fifteen or twenty of those eight hundred companies are working on therapeutic products that they themselves intend to develop); these enabling technologies cost $10 million to $50 million (or more) to develop; and, once mature, they will turn out to be highly valuable to big industrial companies in pharmaceuticals and related sectors like diagnostics. Stellar examples, aside from Micromet, are easy to spot:

MorphoSys: inventor of an antibody generation technology, this venture-backed startup nearly succumbed in the early 2000s to the same shortage of capital that forced Micromet out of Germany, then “went public on a hope and a prayer,” according to one investor. “Now it’s a real company,” he said, with a recent market cap of $420 million.

Direvo: an enzyme engineering business for protein therapeutics sold in 2009 for $230 million to Bayer Schering; the original technology was spun out into the “new Direvo” and is now in innovative use for industrial enzyme development; like the original Direvo, it is based in Cologne.

Jerini: a therapeutics company in Berlin acquired by Shire in 2008 for € 328 million ($521 million).

Brahms: a molecular diagnostics company acquired by Thermo Fisher in 2009 for $479 million.

MTM Laboratories: a molecular diagnostics company in Darmstadt acquired by Roche in 2011 for up to € 190 million ($269 million).

No one doubts Germany’s ability to generate attractive up-and-coming academic projects and small companies.  As one investor put it, “the start-up scene is healthy and ‘well-seeded’ by various grant systems like GO-Bio and government-affiliated institutions such as High-Tech Gründerfonds.”* The bottleneck is capital.

Pharma to the rescue?

Last time I checked, the pharmaceutical industry was shutting down internal research and scouring the world for innovation. Some pharma CEOs are saying that pharma should not invest in internal R&D at all any more. By contrast, pharmaceutical companies are beefing up their corporate VC activities. I count no fewer than twelve VC funds affiliated with pharmaceutical companies, some of which have roots in Germany (Boehringer Ingelheim) or German-speaking Europe (Novartis) and some of these have a strong interest in clinical diagnostics (Roche).

All these funds need look no further than Germany. What a fit! On top of the fertile environment for technologies, labor is relatively cheap. As I learned as a venture capitalist in a Germany-based fund, the cost of a laboratory worker in Germany is roughly half of the cost in the United States and the quality of their work is as high if not higher.

And the managers needed to bring technology platforms to proof of concept are present in larger numbers than at any time in the country’s history. They have worked by the dozens in German companies that have had solid exits – starting with Micromet and extending to Brahms, MTM Laboratories, Direvo, Jerini and MorphoSys – and strong sales – Evotec, Miltenyi and Qiagen in addition to the local pharmaceutical industry (Bayer Schering, the former Sanofi Aventis, and Boehringer Ingelheim).

The growth capital bottleneck should present no major obstacle to corporate venture investors who are both investing more and also increasingly working side-by-side in companies such as Aileron Therapeutics and Celladon Corporation, US-based companies that have attracted four corporate VCs each.

If pharma is the investor then the exit could well be integration into one or another pharma company’s own research efforts. Investing with the aim of achieving technical proof of concept in therapeutics or early commercial validation in the case of non-therapeutic platforms would alleviate the need for fifteen years of funding. The “harvest” could come much earlier. But who knows? Once investors see that their efforts are being rewarded, they might choose to let the companies carry on independently, issuing technology dividends and financial dividends alike.

What’s missing is a catalytic action on the part of those VCs, especially corporate VCs, already active in Germany together with the German government. A government co-investment growth fund of € 200 million or € 300 million, actively managed and investing in each deal alongside a minimum of two corporate or financial VCs, could make a huge difference. The seedlings are beginning to grow. Time to water them.

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Disclosure: Steve Dickman or CBT Advisors have worked recently with Curetis, Direvo and Probiodrug and previously with Evotec, Jerini, MorphoSys and NOXXON.

*GO-Bio has financed thirty-four projects in four rounds, leading to fifteen companies. High-Tech Gründerfonds, also based in Berlin, which finances high-tech startups including those in medical technology- and healthcare-related fields, has been active since 2005 and recently began investing a second fund of € 288.5 million.

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Biogen Idec Lets Stromedix Do the Hard Part

Stromedix’ Exit to Drug’s Source Shows Why We Need VC More Than Ever

by Steve Dickman, CEO, CBT Advisors

February 14, 2012

For anyone wondering about the value that can be added by entrepreneurs and venture capitalists to the drug discovery and development process, look no further than Stromedix. This venture-backed company in Cambridge, MA, was acquired today by Biogen Idec for $75 million up-front and up to $487.5 million based on the achievement of certain development and approval milestones. The driver for the acquisition is a monoclonal antibody known as STX-100, about to enter Phase 2 in the tough indication of idiopathic pulmonary fibrosis (IPF), a nearly always fatal disease characterized by lung scarring. STX-100 is one of several early entrants in the race to apply modern biologic therapies to fibrosis and its challenging biology.

Now let’s consider the value-add. First the return. As of early 2011, Stromedix had raised $29.4 million plus at least an additional $5M in debt financing in September, 2011, most of which has likely not been drawn down. (Stromedix investor Bruce Booth of Atlas Venture states in his blog post that the total cash in, including the debt facility, was $38 million). That makes the up-front price worth about 2X to the Stromedix investment syndicate, which includes NLV Partners, Bessemer Venture Partners, Red Abbey Venture Partners and Frazier Healthcare Ventures as well as Atlas Venture. Considering that most of this capital did not flow in until the 2008 Series B round, that’s not a bad internal rate of return (IRR) for the investors. If STX-100 hits any milestones at all, that return will rise, of course, possibly to an impressive 5X or even, in the unlikely event that all milestones are achieved, 19X. For the venture investors, the combination of certainty of the initial exit and possible upside later – with no more board meetings to attend! – makes this deal a sweet one.

Stromedix logoBut the deal becomes even more impressive – and instructive – when one considers that the asset STX-100, which comprises essentially the full value of Stromedix, was in-licensed from Biogen Idec back in 2007 for a price that I’ve heard was less than $5 million and perhaps even less than $2 million up front. This would fit with the company’s financing history. Before the 2008 $25 million Series B round, less than $5 million had been raised, some of which went to pay salaries, rent and development costs. So not much of this could have paid for the asset. One assumes that Biogen Idec had some milestones and royalties coming to it from the initial licensing deal and that these were negotiated away as part of the sale transaction. But the fact remains: Biogen Idec gave up the asset for a very low price and is buying it back for a much higher one. Why?

Read the rest of my post on Xconomy here or click/copy-paste the link:


http://www.xconomy.com/boston/2012/02/14/biogen-idec-lets-stromedix-do-the-hard-part/?single_page=true

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Startup Targets Sweet Spot for Consumer Health: Connecting You With Your Data

By Steve Dickman, CEO, CBT Advisors

One secret to both improving consumer health and making money in healthcare IT is the feedback loop: providing a person with her own data as a way to improve compliance and performance. Once she knows, for example, that this meal or that workout leads to success, there is a strong incentive to follow a regimen, make appropriate changes, and then look again. Until recently, feedback loops were clunky. A daily weigh-in. An annual physical. But consumers – dieters, runners, the health-conscious – want much more frequent, high-quality and personalized feedback.

Boston-area newco Segterra is forging new territory with its product www.InsideTracker.com. Segterra is the first to offer healthy consumers a regular glimpse of their own biomarker data coupled with data-driven recommendations for diet and exercise. In exchange for a one-time payment ranging from $169 to $249, InsideTracker provides a blood test (performed at work or home if you are in Massachusetts) and compares the results for key markers with population norms. As Segterra CEO Lee Gartley stated last month in the Boston Globe’s InnoEco blog, “…the online test results ‘show you your levels on a set of biomarkers that we’ve identified as being important for overall health and fitness, like glucose, cholesterol, calcium, and vitamin D… Your levels of creatine kinase, for instance, can tell you whether you have muscle damage from biking too far or bench-pressing a few too many pounds. The report can also suggest foods that can counteract low levels of a particular vitamin or mineral, or ways to vary your exercise regimen for the best results.”

"The Measured Life"The founders of Segterra learned from the positive examples of successful HIT startups FitBit and RunKeeper. Each of these also depends on consumer’s own data to provide recommendations and create a feedback loop. But unlike these other companies, Segterra collects data that consumers could not measure any other way and then applies its analytics to that data in ways that will yield increasing benefits the more consumers sign up.

Given the growing number of tools available, we expect this trend of self-measurement to surge.

As an advisor to this company, I have a stake in their success. But this in turn provides a special opportunity for my readers. Respond in the comments and include your email address and I will send you a discount code good for $50 off the first test. Don’t worry, I will not publish your email address. I’ll certainly be interested in your experience with InsideTracker. (The service works for those who have access to a clinical lab in the United States – stay tuned for international offers).

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Partnering360: A New Social Network Aims At Biotech – And Succeeds

By Steve Dickman, CEO, CBT Advisors
October 31, 2011

We recently test-drove a new social network for biotech and pharma executives that meets a real need. The new network is called Partnering360. It was launched today by conference organizer EBD Group to coincide with the start of the BioEurope conference in Düsseldorf.

Yet MORE social networks? After Facebook, LinkedIn, Twitter, Foursquare, Quora (for nerds), Mindbloom (for spiritual networking), Xing (for silent Europeans) and Google+ (no one has figured out yet what this one is for), hasn’t that trend peaked? We think it hasn’t and P360 demonstrates why that is the case.

Before detailing what makes this network look like it will be a winner, let’s think about this apparent paradox: an organization that makes its business out of in-person partnering events is joining the headlong rush into online social networking. What are they thinking?

The thinking is actually quite clear. The people who attend partnering events are a self-selected group. They already want to be with each other. They are interested in meeting more people like them in social as well as professional settings. And their organizations often insist that they use the in-person partnering events to broaden their networks in hopes of landing new opportunities. In-person networks get bigger not just through actual partnering meetings but also via social connections – meeting at breakfast, at coffee breaks or at the evening mixers.

But those connections are often fragile. Sometimes they are not immediately work-related. And unless one is a stickler for saving and logging business cards in a contacts database and then following up, the fleeting contacts can easily be lost.

Enter Partnering360. The only participants in this network are people who have attended this group’s events – 14,000 of them at the outset. (Additional industry players may be able to join by invitation later.) Participation is not mandatory but in the early going, Anna Chrisman of EBD Group told me, hardly anyone is opting out. (Good move making the opt-in the default – that makes the platform much more useful). So there is less worry than usual about meeting the “wrong” kinds of contacts e.g. time-wasters. The “right” contacts are all there. And the software, similar to that of LinkedIn, makes it easy to find people and request to connect with them.

The Partnering360 platform, which has been months in the making, grew out of the observation by those at EBD Group that conference participants had flocked to the online partnering platform, called PartneringONE, which had been set up for the group’s frequent events. But the participants had no way to maintain their connections from one event to the next. And PartneringONE’s default was to inform all members of a company’s delegation of each member’s online contacts. That was not a recipe for taking advantage of the serendipity of chance or social meetings.

The rest of the platform is much like LinkedIn, to which some of its content can be linked. It avoids some obvious pitfalls: it costs nothing (charging for this would be a non-starter). It integrates with both LinkedIn and Twitter instead of trying to compete with them. It allows for uploading of a profile photo and other information. If you are on PartneringONE, your profile information will automatically be imported.

Research has shown that one key to benefiting from social networks, online or in-person, is the so-called “weak” connections. As consultant Stuart E. Jackson put it in a mid-October article in Bloomberg Business Week, “The power of weak connections rests on … the assumption: Don’t worry … about having a small number of close friends. Instead, concentrate on making a much larger number of acquaintances—who might be called ‘not-so-close friends.’”  The reason is that this richer and more diverse set of contacts can be a source for all sorts of useful connections. That, of course, is where LinkedIn and social media tools like it come in.Before he started doubting the political import of Facebook and Twitter here, the New Yorker’s Malcolm Gladwell wrote about this power in his prescient 1999 story “Six Degrees of Lois Weisberg” and the point was driven home by social network mavens Nicholas Christakis and James Fowler in their popular book Connected and Christakis’ entertaining TED talk.

Networks that enhance existing professional networks get a +1 (aka a thumbs up) in my book. Here are some areas where this one has room to grow:

  • More promotional information. No, I don’t mean ads. Partnering360 is ad-free and it had better stay that way to maintain its value. But just like web sites, information companies want to share is valuable. Chrisman said that there is a plan to add paid video captures of company presentations and I believe this will be welcomed by the community.
  • Real discussion groups. In my view, LinkedIn has failed at this. It seems like every group I join is soon swamped by unwanted, often overly promotional posts. Or the group goes silent. Twitter does this well but the discussions die off because they are too public and limited to 140 characters. The exclusive nature of P360 should lend itself to some productive discussions. I hope this functionality is added soon.
  • Links to more platforms. I dissed Quora above but in fact it can be useful. Google+ also has promise and shares with Partnering360 some degree of self-selection.

Of course, Partnering360 faces some of the same limitations that any online medium does: this material is legally discoverable. It’s semi-public. It certainly does not enjoy the protection of the high walls of a company’s intranet. Its main challenge is how to get above and stay above the noise. But given how regularly the partnering events occur and how often my readers and I find ourselves attending them, I suspect that this platform is here to stay.

END

Full disclosure: I was a moderator of a social network-related panel (video here) at an EBD event earlier this year and I will moderate another one at BioEurope Spring in Amsterdam in March, 2012.

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Big Pharma Attempts to Extend Own Lifespan by Activating Sirtuins

Sirtuins can’t extend the life of a fly. Can they extend the life of a pharmaceutical company?

By Steven Dickman, CEO, CBT Advisors

Can drugs that supposedly “activate” a controversial target – sirtuin proteins – stop or even reverse the aging process? A new report this week said “No.” According to this report, published Wednesday night in Nature, sirtuin activators do not extend lifespan in roundworms and flies and earlier studies that said they did were flawed. Nonetheless, GlaxoSmithKline (GSK) continues to invest hundreds of millions of dollars into developing drugs to hit these targets – more about their findings below – and if the drugs work, for whatever reason, the scientific squabbles will not matter.

I recently had the chance to hear Harvard professor David Sinclair talk publicly about his and GSK’s research into sirtuin activators. Sinclair was the scientific founder of Sirtris and he reported at a forum on longevity in Cambridge, MA, that GSK has high hopes of near-term confirmation in mice that some sirtuin activators do extend lifespan. Based on its continued investment, GSK still believes that the $720 million acquisition of Sirtris in 2008 was a smart one.

To read the rest of today’s post, visit Xconomy here or copy-paste the link:

http://www.xconomy.com/boston/2011/09/23/big-pharma-attempts-to-extend-own-lifespan-by-activating-sirtuins/

 

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Google Health is Dead, Long Live Google+

A Boston Biotech Watch guest post by Rich Whalley*

(Cross-posted to The Health Care Blog on July 20, 2011)

Now that Google has put its ill-fated Google Health project to rest, we are wondering who will make the next big attempt to establish a personal health record (PHR) platform for healthy people. Many have tried and many have failed, and there is still no popular platform for gathering, analyzing and sharing health data.

Adam Bosworth founded Google Health in 2006 to provide an online place for consumers to store their own health data. Bosworth left shortly thereafter and went on to found Keas, a SF-based web startup which takes a more social approach to tracking one’s health via a competitive point system. In a recent interview on TechCrunch, Bosworth spoke about why he thought Google Health had failed, “It’s not social,” and “Google didn’t push to see what they could do that people would want.”

Google Health failed in part because the user interface did not motivate most users to upload their health data. By contrast, one of the fastest-growing health sites on the internet, PatientsLikeMe.com, has built its online health community to an impressive 105,000 subscribers, focused first on patients suffering from chronic diseases like ALS (Lou Gehrig’s disease). The implied reward for this was high given the unmet health need, so it was an easy choice for patients to take the time to enter their valuable data. Healthy people have no such incentive for using PatientsLikeMe, but many seem to want to get in on the action. Armed with smartphones and social network memberships, a new health-savvy generation is looking to catalyze the growth of a new movement.

For every startup entering this field, the million dollar question is “just how easy can we make it for people to enter data and track their health?” It practically has to be automated in order to go viral, a prerequisite for aggregating the “big data” that could lead to marketable conclusions. There is a new line of VC-backed startups tackling this daunting task.

Withings internet-connected scale

Coming to a Twitter feed near you

Withings, based in France, has produced a Body Mass Index (BMI) weight scale which tracks BMI via iPhone or computer and even sends automatic tweets. Americans can get in-shape, and French people can laugh at the tweets of overweight Americans. With all parties happy, why haven’t we seen more development in this area of diagnostic innovation for healthy people? For one, there’s a large VC question around whether or not these startups can make a large ROI with their one-trick ponies. Won’t they be killed off by apps or hardware add-ons created for next-generation smart phones?

Consider Fitbit, a small, lightweight device that functions as a pedometer that tracks sleep and burnt calories throughout the day. One could argue that a small body clip is much more comfortable to wear than an iPhone 4, but Fitbit is primarily a consumer software play. Its hardware is no more than a tricked-out accelerometer, not unlike the ones found inside Nintendo Wii controllers. Recalling Flip Video, I can’t help but think the VCs at Softtech and True Ventures are losing some precious Fitbit-measured “actual sleep time” over certain prickly questions. Will next-gen smart phones eventually eat up FitBit’s market? Will Fitbit be lucky enough to get an exit before time runs out?

Sleeping Guy

Looking to share data on a universal personalized health platform? Dream on!

Withings, despite being partnered with the late Google Health, seems to have a flop-proof strategy of targeting diagnostic applications that are unlikely to be eaten up by new-fangled mobile devices. They recently released an FDA-approved blood pressure monitor that connects directly to the iPhone, and more impressively, already have two products on the market – with a baby monitor expected to hit the market later this year. While they may not be making big returns just yet, they might be able to become a leader in this space by putting up a solid enough barrier to entry.

What would need to happen for these companies to really take off? It’s probably going to involve a concerted effort from players in social networking to form better integrated health networks – a place for the data to live. Even though Google Health flopped, Adam Bosworth seems pretty confident about his new gig, but Keas is not exactly going viral just yet. So who’s left to take charge of the movement?

Google Health recycled

Is Google Health really going to waste, or will it be strategically recycled into a 100% post-consumer product?

PatientsLikeMe is currently limited to the chronically ill, and Facebook doesn’t seem to be making strides in this direction anytime soon. One of the most promising new platforms is Google+, termed “the Facebook killer.” If successful, Google has a golden opportunity to use Google+’s platform to provide a framework for people to manage personal healthcare data. For example, Circles allows users to select specific people and groups for sharing personal data of all varieties, including health data. Importantly, the platform can aggregate anonymized data across a very large user base. Will Google+ eventually become the personal health data platform? I would love to see this happen, but so far there is no hint that anyone at Google is working on healthcare apps for Google+. We can’t wait to see some startups tackle this. It’s only a matter of time.

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Bugs 1, Humans 0: “Antibiotics: The Perfect Storm” by David M. Shlaes

Feb. 3, 2011

A Boston Biotech Watch Book Review

By Steve Dickman, CEO, CBT Advisors

The rise of super-resistant bacteria and the inadequate attempts to combat them: Who but David Shlaes could give us such an entertaining and wide-ranging book, Antibiotics: The Perfect Storm, on such a gloomy topic? Shlaes, a top consultant working on the discovery and development of antibiotics, brings an encyclopedic and wry perspective to a field that, for pharma anyway, has mostly fallen between the cracks.

David M. Shlaes, antibiotics expert The broad outlines of the antibiotics tragedy-in-the-making are familiar: overuse and misuse of antibiotics has combined with a slowdown in new drug research to create what Shlaes aptly calls a “perfect storm:” more powerful and versatile bugs are morphing into existence daily, it seems, but the drugs to combat them have ceased to reach the market, felled by irrational regulators and markets not huge enough for Big Pharma. Consequently, we overuse those antibiotics that are still effective, which elicits resistance and then leads to disaster: the spread of multiply resistant superbugs and no way to stop them.

Just two new classes of antibiotics have reached the market in forty-two years, writes Shlaes: linezolid (Zyvox, Pfizer), belonging to the oxazolidinone class, and daptomycin (Cubicin, Cubist), a cyclic lipopeptide. Meantime, the “perfect” bug, equipped with resistance to every known antibiotic, creeps ever closer. In August of last year, reports surfaced about Enterobacteriaceae (gut bacteria) sporting a gene that codes for a penicillin-busting enzyme called NDM-1. The bacteria were found in Pakistan, India and the United States and only a single, old-school, kidney-toxic antibiotic, colistin, showed activity against it.

This sad state of affairs was predicted by Shlaes, who has long been on a crusade to loosen the logjam of unhelpful regulations, especially in the United States. The man is ideally suited to lead the charge. He started out in academia, realized after sixteen years that if he wanted to change the world he had to move into the pharmaceutical industry and then embarked on a successful career as an executive with Wyeth, where he was vice president in charge of infectious disease. From that lofty post, he dove into biotech and worked for Cambridge, MA-based Idenix Pharmaceuticals and joined the board of Novexel in France. He is now a Connecticut-based consultant.

Antibiotics: The Perfect Storm imagePlenty of industry consultants are on their game; few write books. Shlaes became one of this select group because he is deeply passionate on the dual subjects of improving antibiotics R&D and increasing new drug approvals, and he wants to let his passion move others to action.

The major culprit in Shlaes’ mind – and in the views of some antibiotics-savvy venture capitalists interviewed for this article – is the Food and Drug Administration (FDA). FDA has, according to Shlaes, thoroughly messed up its mandate. Shlaes sees three main issues that have plagued the agency for most of the antibiotics drought of the last two decades:

  • FDA has increased clinical trial design stringency to the point where trials become so large that they no longer pay. At the same time, FDA adheres, despite recent progress in some hearings at which Shlaes has presented, to outdated standards for approval. For instance, these include mortality endpoints in community-acquired pneumonia that date from the 1930s and have long since been superseded by other, more up-to-date and realistic measures.
  • Because these drugs work so well when they work, there is a double standard for anti-infectives compared to other drug classes. “Tylenol,” Shlaes writes on page 40, “is one of the most widely used drugs in the world … and causes more cases of acute liver failure requiring liver transplant than any other drug. It is still sold without prescription worldwide.” By contrast, antibiotics such as Ketek in sinusitis and bronchitis, which have much lower complication rates, have nonetheless had their marketing approval withdrawn.
  • Most troublingly, FDA continues to “move the goal posts” in mandating one set of endpoints early in a new antibiotic’s development and then increasing the requirements as the antibiotic moves closer to approval. Shlaes experienced this firsthand in his years at Wyeth and it has clearly left a bitter taste. One hopes we all benefit from the crusader’s zeal he brings to improving this unhappy state of affairs.

Pharma is a second culprit. Pharma consolidation has gone so far that the revenues from even a top-selling antibiotic barely move the needle. The largest-selling antibiotic in history, Augmentin, peaked at just under $2 billion. By contrast, Shlaes points out, Pfizer and Wyeth had combined 2008 revenues of $71.1 billion. So the economic incentive to try to bring forward new antibiotics is not as strong as Shlaes would like. At the moment, there is a shift occurring in pharma’s thinking, of course, away from blockbusters and toward smaller-market opportunities such as orphan drugs. I imagine that there could be good reason to expect pharma to become more interested in moving back into antibiotics after abandoning them; Shlaes writes that there is no evidence of this.

Shlaes is too heavy-handed in his critique of the biotech response to the antibiotics crisi. It would be nice to have a couple of case studies of biotechs that succeeded (such as Vicuron, acquired in 2005 by Pfizer for $1.9 billion) instead of (1) a blanket statement like “some experts predict that only 10% of biotech companies will succeed” in antibiotics development; and (2) a single case study of one such failure, a Colorado company called Replidyne, that was killed off in large part by FDA moving the goal posts.

A closer look at Achaogen and Tetraphase (in Watertown, Massachusetts), mentioned briefly, would have yielded a rich vein of hope. Both companies have managed to raise large amounts of venture capital money despite all the challenges. Achaogen, based in South San Francisco, has even succeeded at raising as much non-dilutive capital as any private biotech I’ve ever heard of, well over $100 million, from sources such as the U.S. military and the Wellcome Trust. The forces arrayed against successful marketing of new antibiotics can be overcome, these companies’ investors believe, through conducting clever clinical trial strategies (Achaogen) and inventing unique chemistries (Tetraphase). That is a story worth hearing and it would be interesting to hear Shlaes tell it.

In addition to the role of these biotechs, other areas I wish Shlaes had touched on include:

  • The epidemic of hand-washing with “anti-bacterial” soaps and its implications for the rise of resistant bacteria
  • The role for improved, genomics-based diagnostics in the clinical care of infected persons or those at risk
  • The role of genetics-based susceptibility on the part of some of us to certain subsets of the bacteria out there
  • Potential contributions by academic consortia in filling the gaps left by the vanished big pharma research and development programs
  • A view of antibiotics development through the prism of healthcare costs – stays in sealed intensive care wards can’t be cheap, so it must be in the interests of the healthcare system to have more impactful tools to fight those nasty hospital-acquired infections, especially now that Medicare is slashing reimbursement to hospitals that do not report them …

It is hard to know what to do next when reading such a persuasive argument for societal action. Found a non-profit? Jawbone a regulator? Invest in more biotech companies that pursue anti-infectives? But one thing is for sure: if Big Pharma and FDA manage to pull themselves out of the current morass, it will be due to Shlaes and his allies in industry and academia exerting their maximally persuasive powers to bring about the unending supply of new antibiotics that society desperately needs.

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Google Meets Healthcare VC

The Boston Biotech Watch Take on Google’s Healthcare Investing Approach Based on an Interview with Google Ventures’ Krishna Yeshwant

by Steve Dickman, CEO, CBT Advisors

Now that most private-company biotech CEOs have given up on “IPO window reopens” and “VC bidding war,” three of the most galvanizing words for someone raising money these days are “Google might invest.” Fund-raising for the CEO of a young biotech is always a war of attrition and corporate VC funds are the current weapons of choice.

It is one thing for cash-strapped management teams to want Google’s shiny new healthcare venture arm to invest. But should Google Ventures invest? Would it be the right thing for Google and the right thing for the sector if they came into more deals? We recently spoke to Google Ventures’ Cambridge-based healthcare representative Krishna Yeshwant, M.D., and we did some reading up on Google, including plowing through Ken Auletta’s widely reviewed (and bombastically titled) book Googled: The End of the World As We Know It“. Now here’s our take not just on what Google Ventures is doing in healthcare but also what we think they should be doing.

(One caveat is that the bulk of investments that Google Ventures will do in the coming years will not be in the healthcare space. The fund ambitiously intends to invest $100M a year into startups and new ventures, and the vast majority of those dollars will flow into IT-related endeavors. Our focus is on the fund’s life sciences- and healthcare-related activities.)

Google Ventures would seem to fit right into the current dominance of corporate VCs within the universe of VC life sciences dealmaking. On the surface, it’s another cash-flush corporate fund wading into VC as part of a parent-company mandate to move up the food chain and generate insight as well as returns. (As if the “generate returns” part isn’t hard enough by itself!)

We think Google Ventures (GV) actually does not fit the typical corporate VC mold at all and, based on its provenance, we think it has the potential to do amazing work. More about our views in a moment. First, we’ll look at how GV sees itself in the context of the deals they’ve already done. Then we will pull back and imagine what GV could do that might let it rise above and make a true mark on the healthcare investing and on healthcare itself.

Krishna Yeshwant photos

Krishna Yeshwant, photos courtesy Google web site

Aside from cleantech, most deals lately in the life sciences and healthcare space are in therapeutics. By and large, GV does not do those. “We are probably not the investors to go after moving a molecule from Phase 2 to Phase 3,” GV’s Yeshwant said. “We are not ready to have a portfolio of molecules. [Furthermore,] it would be hard for us to invest in a single molecule.”

So what does GV do? So far, platforms, as embodied by GV’s first two healthcare deals: Adimab and iPierian. Although the former is on the East Coast and the latter on the West Coast, these companies have a few things in common. Both are funded by top-tier life science investors (Polaris, SV Life Sciences, Orbimed in Adimab; Highland Capital, Kleiner Perkins, MPM Capital in iPierian). Both are working on groundbreaking platforms and own enormous amounts of potentially valuable IP. Adimab works on antibody therapeutics; iPierian is a novel stem-cell-biology company with a big vision for overhauling the current clinical trials process by offering streamlined testing on ex vivo platforms derived from a patient’s own stem cells. There is more about Adimab’s and iPierian’s approaches in these linked news articles from Xconomy.

The companies differ in some key ways that give us some insight into GV’s parameters: Adimab is run by a charismatic and battle-tested CEO, Tillman Gerngross, who successfully sold his previous company GlycoFi to Merck in 2008 for $400M and thereby provided investors with a return of 9X or better. So in some sense, it’s a “bet on the jockey” play in the crowded space of antibody platforms. By contrast, iPierian is run by an experienced but not-quite-so-high-profile CEO, Michael Venuti, and in fact let go of its previous CEO, John Walker, the month before GV invested.

Tillman Gerngross, Dartmouth engineer extraordinaire

Tillman Gerngross, Dartmouth engineer extraordinaire

“We are clearly attracted to platforms,” said Yeshwant. “We can understand the science, we see the potential {for large exits} based on the early examples that a platform can produce. If there is room for the platform to go beyond what it is doing, we can REALLY get excited about it.”

Avoiding the corporate VC “bump”

In these cases, GV’s preference was not to invest in pure startups but to wait until some experienced investors took the early risk. In one or both of these cases, GV may have “paid up” in order to get into the syndicate. Lest that leave the wrong impression, Yeshwant hastens to explain: “Almost everyone at Google Ventures has started companies and looked at VCs from the other side of the table,” said Yeshwant. “I remember that: when a corporate VC comes in, you look at it as an opportunity to bump your share price. The way we are trying to place Google Ventures is really as an institutional investor. The track record we want to create here is not ‘here comes Google, let’s get a bump on our valuation.’ People LIKE to have us at the table. We are a VC firm that has [access to] a host of programmers and statisticians. We have former programmers on our team who can help our portfolio. Take our user interface experts, for example. This may not be relevant for therapeutics platforms but it might be very relevant for healthcare IT companies. That programmer’s role is to be dropped into some of those companies and create value.”

And yet neither diagnostics nor healthcare IT seem to be on GV’s radar screen yet. Yeshwant: “We are excited about the diagnostics field. We are watching it very closely. [But w]e have yet to find a great investment.” Most life science VCs who have looked at diagnostics would say the same thing – many more have looked than have actually done a deal.

When speaking of healthcare IT, Yeshwant reflects the melancholy wisdom of someone who knows the US healthcare system all too well. Yeshwant is in fact not only an experienced programmer and IT entrepreneur who has founded two companies that were sold to big IT players; he is also a current resident at Harvard Medical School working at Brigham & Women’s Hospital. “The healthcare market still does not really make sense [to us as venture investors]. Working in a hospital, we [as physicians] try our best to do what is right for the patient but the patient is only one of our customers. That distorts what [GV] as a service business [or investor in service businesses] can do. That setup does not let us get into this natural harmony of a company that can really serve the needs of the consumer and succeed because they did a good job by the consumer. As a medical doctor, I want to serve my patients, but it is very difficult to conceive of a great IT company [in this space]. There are so many needs IT can serve that would help patients. But what is the business model that does not involve so many confusing different stakeholders?”

Yeshwant has similar reservations about companies developing electronic medical records (EMRs) despite the inclusion of EMR subsidies in the stimulus and health care reform packages. “Despite a lot of money coming in from the government, it is not clear that the opportunity is really there yet,” he said. “Yes, that government money will drive M&A activity and there are ideas being thrown back and forth. We do not feel compelled yet by the companies we have seen.”

A common theme across all areas in which GV is considering is its very high bar for investing. Indeed, it has been nearly three months since our conversation with Yeshwant and GV has not announced a single new life sciences deal. Although it is inappropriate to draw conclusions from this absence of announcements (a flurry of new deals could be announced next week), the fund’s measured pace reflects the realities of being a VC in 2010 – when a lot fewer new-money deals are closing than in the years between, say, 2003 and 2007 – and the realities of being Google.

When we asked Yeshwant whether Google Ventures would prefer to start companies on its own rather than wait to be shown “doable deals” by the VCs in its network, Yeshwant cited the fund’s need to stay on the right side of its sole limited partner, Google itself: “Especially in healthcare, we are still looking for those [right] companies [for us]. We are looking for the entrepreneurs, the teams that will make those companies great. We are meeting a bunch of entrepreneurs and VC folks. If there is something we can put a good thesis around, then, yes we would be open to starting something, seeding a company and incubating it. We are still a bit early – we’d hate to hastily put something like that together and have it fall apart. That would sour Google proper. So for now we have to have a very high threshhold.”

Reluctance? What reluctance?

Googled book jacketWe think the threshhold does not have to be so high. This is where our recommendation comes in. From reading Ken Auletta’s book

Googled: The End of the World As We Know It, we were reminded of Google’s roots and its winding path to $23 billion in 2009 revenues. The company is an advertising behemoth with now 99% of those revenues coming from ad sales. And the ethos underlying Google’s birth is still true for its many new ventures:

  • We are engineers.
  • We are scientists.
  • We want to change the world.

Auletta’s book shows that Google is all about two mentalities: the engineer on one hand; the consumer-minded marketeer on the other. Sometimes – as when the founders built the first search engine – these are embodied in the same person. More often the roles are played by different people within the company’s leadership. The process works like this: the engineer comes up with an idea about what is technically doable and at the same time inherently elegant; the marketeer relentlessly orients it toward the “real user.” Born of a dynamic tension between these two forces, product after product has emerged from Google (think Google News, Google Earth, Gmail and Google Maps and) More recently, products and technologies have been acquired to take advantage of perceived opportunities (Android, YouTube).

Admittedly, it is hard to see how either mentality – better engineering, better consumer focus – will work in healthcare investing unless and until the healthcare system is reformed to be more responsive to incentives, more consumer-driven and especially more data-driven. The Google fund would seem to be able to apply its overwhelming leverage more efficiently in other fields – mobile computing, location-aware mobile apps, data storage and retrieval, even hardware – at least for now.

At the same time, the apparent hesitation by the GV team to do most healthcare deals and especially to start companies of its own – the “high bar” that Yeshwant was talking about in our interview – strikes us as inconsistent with the basic premise of the fund’s corporate parent. There seems to be a reluctance – if not an all-out refusal — to get too involved in truly risky deals that at the same time could be truly transformative. After all, in the letter that accompanied their 2004 IPO filing, the Google founders themselves wrote that they are looking to “make big investment bets” on technologies that have only a 10% chance of achieving a billion-dollar level of success. To paraphrase the loud, lascivious Sean Parker character in the hit movie “The Social Network,” “You guys think it’s all about making a million dollars?! It’s not. Think billion, baby!”

WWGD?

What we have heard from Yeshwant (echoed in this interview published by Wade Roush of Xconomy back in May, 2010) sounds not much different from what we hear from generic corporate VCs. What we’d love to see instead would look more like this:

  • More attention from the top: You want to change the world, Sergey & Larry? Pay attention to healthcare.
  • More experiments in combining bandwidth with healthcare. The Google project to “wire” a US city with ultrahighspeed broadband capability comes to mind. There have to be HC opportunities in that, perhaps in conjunction with an existing startup or a new one
  • Pioneering programs outside the developed world that, for relatively low initial investments can improve upon technologies initially developed here and roll them out in developing-country markets. Then, when the “boomerang” comes back (see our earlier post on “boomerang” technologies), Google will be thinking ahead about how to make money on these technologies in the developed world.
  • Start more companies! Forget the “high bar” and the “sour taste”. Instead, use your cachet and market power to start companies that might take a while to incubate but that can be truly transformative. This is already the approach of some top-tier US-based pharma company VC funds who have told us that they have grown impatient waiting for VC syndicates to form from the ever-shrinking pool of active VCs, so they’ve begun to dive in and fund the companies they want to see all by themselves.
  • Focus on diagnostics. Yes, Yeshwant said GV has not seen its favorite deal yet. But Yeshwant himself wrote an award-winning business plan for a company, Diagnostics for All, that could provide a valuable prototype. That company, which we highlighted in our blog post on “boomerang” technologies, is working on filter-paper-based diagnostic kits that can be manufactured for pennies. And Google founder Sergei Brin invested in personal genomics company 23andme.com, an investment now owned by Google itself.
  • See our “shopping list” below for specific opportunities

We hope GV does all of these things. Because of its potentially long time horizon and its amazing market power in search and advertising, GV has a huge advantage over traditional VC funds. The exit from most of these businesses will be traditional ones – IPO or, more likely, trade sale – but another potential exit could be the creation of a new business unit for Google.

Church sign: "THERE ARE SOME QUESTIONS THAT CAN'T BE ANSWERED BY GOOGLE"

But not as many as there used to be

Right now, with the convergence of high-powered data collection through genomics and better sensors; better analysis of that data using high-powered computing; and a reorientation of the healthcare system toward prevention, there is no limit to what an active and visionary investor could achieve. To us, the potential for improving actual human health by taking advantage of available data is endless – and Google’s own track record in improving data access makes it an ideal player.

Therefore we’d encourage Google Ventures as follows:

  • Think long-term, not near-term.
  • Think big, not small.
  • Focus more on strategic and societal benefit.
  • Reach for the stars.

END

TABLE 1: A HEALTHCARE   SHOPPING LIST FOR GOOGLE VENTURES
  • Personalized medicine
  • Computer-aided medical devices
  • The “human-machine interface” in medical devices
  • Electronic medical records
  • Global health (investments in “boomerang” technologies would be perfect for GV – they will have the time & patience to wait for the boomerang to come back)
  • Analysis of “Big Data” e.g. from patients or payers that could rationalize the US healthcare system or piggyback on the move toward comparative effectiveness

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We are our bugs – hot Boston startup mines the gut

by Steven Dickman, CEO, CBT Advisors

Seeing the human being as a “superorganism” composed primarily of freeloading or symbiotic bacteria and other parasites and designing products accordingly – that is the basis for a new startup with the alluring name of Libra Biosciences being incubated by PureTech Ventures in Boston.

Daphne Zohar, PureTech Ventures

Daphne Zohar, top Boston innovator

News of Libra began to come out in a piece in yesterday’s (Oct. 4, 2010) Boston Globe citing PureTech managing partner Daphne Zohar as one of Boston’s top 15 innovators. Little else is publicly available about the startup except a one-page web site stating that the company will be active in diagnostics and consumer products as well as therapeutics. Disease areas will include developmental, immunological and epithelial disorders.

The idea of humans and other eukaryotes as walking sacs of bacteria is not new. It was raised elegantly by Lewis Thomas in his seminal and delightful 1978 book Lives of a Cell: Notes of a Biology Watcher.

Libra Biosciences logo
Nor would this be the first time someone tried to apply this concept to predictive disease modeling – witness this paper from Nicholson et al. in Nature Biotech in 2004 exploring applications of “omics” to human-residing bacteria. But this appears to be the first time that commercial activity has coalesced around this interesting field of science, likely driven by advances in high-speed genetic sequencing. (The latest presentation we’ve seen from BGI – formerly Beijing Genomics Institute – reports that BGI alone will have increased to 5 TB of genome sequenced per day – that’s 1500 human genomes – by the end of 2010, up from 100 GB a day at the end of 2009.) There have been some interesting publications pointing to links between the nature of gut bacteria in individuals and their weight. According to these studies, as reported in the Los Angeles Times in June of this year, the more efficient the gut bacteria are at processing food, the more overweight the hosts are. We prefer the inefficient ones!

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Except for the brief mention in the Globe today, Libra is not talking to the media just yet. But this interesting piece of startup news confirms PureTech’s role – alongside Third Rock Ventures and just a handful of other Boston-based firms – as one of the few key bridges across the current yawning gap separating creative academic science and fundable biotech companies.

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