I-Corps at the NIH: Evidence-based Translational Medicine

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We have learned a remarkable process that allow us to be highly focused, and we have learned a tool of trade we can now repeat. This has been of tremendous value to us.

Andrew Norris, Principal Investigator BCN Biosciences

Over the last three years the National Science Foundation I-Corps has taught over 700 teams of scientists how to commercialize their technology and how to fail less, increasing their odds for commercial success.

To see if this same curriculum would work for therapeutics, diagnostics, medical devices and digital health, we taught 26 teams at UCSF a life science version of the NSF curriculum. 110 researchers and clinicians, and Principal Investigators got out of the lab and hospital, and talked to 2,355 customers. (Details here)

For the last 10 weeks 19 teams in therapeutics, diagnostics and medical devices from the National Institutes of Health (from four of the largest institutes; NCINHBLI, NINDS, and NCATS) have gone through the I-Corps at NIH.

87 researchers and clinicians spoke to 2,120 customers, tested 695 hypotheses and pivoted 215 times. Every team spoke to over 100 customers.

Three Big Questions
The NIH teams weren’t just teams with ideas, they were fully formed companies with CEO’s and Principal Investigators who already had received a $150,000 grant from the NIH. With that SBIR-Phase 1 funding the teams were trying to establish the technical merit, feasibility, and commercial potential of their technology. Many will apply for a Phase II grant of up to $1 million to continue their R&D efforts.

Going into the class we had three questions:

  1. Could companies who were already pursuing a business model be convinced to revisit their key commercialization hypotheses – and iterate and pivot if needed?
  2. Was getting the Principal Investigators and CEO out of the building more effective than the traditional NIH model of bringing in outside consultants to do commercialization planning?
  3. Would our style of being relentlessly direct with senior scientists, who hadn’t had their work questioned in this fashion since their PhD orals, work with the NIH teams?

Evidence-based Translational Medicine
We’ve learned that information from 100 customers is just at the edge of having sufficient data to validate/invalidate a company’s business model hypotheses. As for whether you can/should push scientists past their comfort zone, the evidence is clear – there is no other program that gets teams anywhere close to talking to 100 customers. The reason? For entrepreneurs to get out of the building at this speed and scale is an unnatural act. It’s hard, there are lots of other demands on their time, etc. But we push and cajole hard, (our phrase is we’re relentlessly direct,) knowing that while they might find it uncomfortable the first three days of the class, they come out thanking us.

The experience is demanding but time and again we have seen I-Corps teams transform their business assumptions. This direct interaction with potential users and customers is essential to commercialize science (whether to license the technology or launch a startup.) This process can’t be outsourced. These teams saved years and millions of dollars for themselves, the NIH and the U.S. taxpayer. Evidence is now in-hand that with I-Corps@NIH the NIH has the most effective program for commercializing science.

Lessons Learned Day
Every week of this 10 week class, teams present a summary of what they learned from their customers interviews. For the final presentation each team created a two minute video about their 10-week journey and a 8-minute PowerPoint presentation to tell us where they started, what they learned, how they learned it, and where they’re going. This “Lessons Learned” presentation is much different than a traditional demo day. It gives us a sense of the learning, velocity and trajectory of the teams, rather than a demo day showing us how smart they are at a single point in time.

BCN Biosciences
This video from team BCN Biosciences describes what the intensity, urgency, velocity and trajectory of an I-Corps team felt like. Like a startup it’s relentless.

BCN is developing a drug that increases anti-cancer effect of radiation in lung cancer (and/or reduces normal tissue damage by at least 40%). They were certain their customers were Radiation Oncologists, that MOA data was needed, that they needed to have Phase 1 trial data to license their product, and needed >$5 million and 6 years. After 10 weeks and 100 interviews, they learned that these hypotheses were wrong.

If you can’t see the BCN Biosciences video click here

The I-Corps experience helped the BCN Bioscience team develop an entirely new set set of business model hypotheses – this time validated by customers and partners. The “money slides” for BCN Biosciences are slides 22 and 23.

If you can’t see the BCN Biosciences presentation click here

You Can’t Outsource Customer Discovery
What we hear time and again from the Principal Investigators is “I never would have known this” or “I wouldn’t have understood it if I hadn’t heard it myself.” Up until now the NIH model of commercialization treated a Principal Investigator as someone who can’t be bothered to get out of the building (let alone insist that it’s part of their job in commercialization.) In the 21st century using proxies to get out of the building is like using barbers as surgeons.

Clinacuity
While the Clinacuity video sounds like an ad for customer discovery, listen to what they said then look at their slides. This team really learned outside the building.


If you can’t see the Clinacuity video click here

Clinacuity’s technology automatically extracts data in real-time from clinical notes, (the narrative text documents in a Electronic Health Record,) and provides a summary in real time. Their diagrams of the healthcare customer segment in slides 15-18 were outstanding.

If you can’t see the Clinacuity presentation click here

GigaGen
The GigaGen team – making recombinant gamma globulin – holds the record for customer discovery – 163 customer interviews on multiple continents.

If you can’t see the GigaGen video click here

GigaGen’s learning on customer value proposition and who were the real stakeholders was a revelation. Their next-to-last slide on Activities, Resouces and Partners put the pieces together.

If you can’t see the GigaGen presentation click here

Affinity Therapeutics
Affinity came into class with a drug coated Arterial Venous Graft – graft narrowing is a big problem.

One of things we tell all the teams is that we’re not going to critique their clinical or biological hypotheses. Yet we know that by getting out of the building their interaction with customers might do just that. That’s what happened to Affinity.

If you can’t see the Affinity video click here

Affinity was a great example of a team that pivoted their MVP. They realized they might have a completely new product – Vascular wraps that can reduce graft infection.  See slides 17-23.

If you can’t see the Affinity presentation click here

Haro
Haro is making a drug for the treatment of high risk neuroblastoma, the most common extracranial cancer in infancy and childhood. On day 1 of the class I told the team, “Your presentation is different from the others – and not in a good way.”  That’s not how I described them in the final presentation.

If you can’t see the Haro video click here

After 120 interviews the Haro found that there are oncology organizations (NCI-funded clinical development partners) that will take Haro’s compound and develop it at their own expense and take it all the way into the clinic. This will save Haro tens of millions of dollars in development cost.  See slides 12 and 13.

If you can’t see the Haro presentation click here

Cardiax
Caridax is developing a neural stimulator to treat atrial fibrillation. Their video points out some of the common pitfalls in customer discovery. Great summary from Mark Bates, the Principal Investigator: “You don’t know what you don’t know. Scientific discovery is different than innovation. You as a prospective entrepreneur need this type of systematic vetting and analysis to know the difference.”

If you can’t see the Cardiax video click here

After 80 interviews they realized they were jumping to conclusions and imparting their bias into the process. Take a look at slides 8-11 and see their course correction.

If you can’t see the Cardiax presentation click here

The other 15 presentations were equally impressive. Each and every team stood up and delivered. And in ways that surprised themselves.

The Lean Startup approach (hypotheses testing outside the building,) was the first time clinicians and researchers understood that talking to customers didn’t require sales, marketing or an MBA – that they themselves could do a pretty good first pass. I-Corps at NIH just gave us more evidence that’s true.

The team videos and slides are on SlideShare here.

A Team Effort
This blog post may make it sound like there was no one else in the room but me and the teams. But nothing could be farther from the truth. The I-Corps@NIH teaching team was led by Edmund Pendleton. Allan May/Jonathan Fay taught medical devices, John Blaho/Bob Storey taught diagnostics and Karl Handelsman/Keith McGreggor taught therapeutics. Andre Marquis, Frank Rimalovski and Dean Chang provided additional expertise. Brandy Nagel was our tireless teaching assistant. Jerry Engel is the NSF I-Corps faculty director.

Special thanks to Paul Yock of Stanford Biodesign and Alexander Osterwalder for flying across the country/world to be part of the teaching team.

I created the I-Corps/Lean LaunchPad® syllabus/curriculum, and with guidance from Allan May, Karl Handelsman Abhas Gupta and Todd Morrill adapted it for Life Sciences/Health Care/Digital Health. The team from VentureWell provided the logistical support. The I-Corps program is run by the National Science Foundation (Babu Dasgupta, Don Millard and Anita LaSalle.) And of course none of this would be possible without the tremendous and enthusiastic support and encouragement of Michael Weingarten the director of the NIH/NCI SBIR program and his team.

Lessons Learned

  • The I-Corps/Lean LaunchPad curriculum works for therapeutics, diagnostics and device teams
  • Talking to 100 customers not only affected teams’ commercial hypotheses but also their biological and clinical assumptions
  • These teams saved years and millions of dollars for themselves, the NIH and the U.S. taxpayer
  • Evidence is now in-hand that the NIH has the most effective program for commercializing science
  • In the 21st century using proxies to get out of the building is like using barbers as surgeons

Engineering a Regional Tech Cluster-part 3 of 3 of Bigger in Bend

Dino Vendetti a VC at Bay Partners, moved up to Bend, Oregon on a mission to engineer Bend into a regional technology cluster.  Over the years Dino and I brainstormed about how Lean entrepreneurship would affect regional development.

I visited Bend last year and caught up with his progress.

Today with every city, state, country trying to build out a technology cluster, following Dino’s progress can provide others with a roadmap of what’s worked and didn’t.

Here’s Part 3 of Dino’s story…


As a transplanted Silicon Valley VC and now a regional investor, I often get asked, “How do we go about building up our local tech ecosystem?”

The short answer is, “One step at a time.”

In the beginning in Bend, “necessity was the mother of invention.” Local entrepreneurs just made it up as they went. But today we are intentionally engineering six distinct activities to support this tech cluster: entrepreneurial density, university, transportation, capital, accelerator, and business community.

Let’s look at each of these six elements in more detail and I’ll explain what we have been doing in Bend to accelerate each of these.

1. Entrepreneurial Density:
Density – the connection of like-minded firms and their support services – is a critical component of a cluster. The most fertile source of entrepreneurs is the population of existing entrepreneurial companies. But for clusters without sufficient firms you first need to attract companies to your region. However, it’s difficult to create density overnight. Entrepreneurs need to understand and believe the reasons why they should want to cluster in your region given there are other alternatives (nationally Silicon Valley or New York; regionally Seattle and Bellevue, Portland and Bend).

In addition to technical and entrepreneurial talent, a region also needs experienced executive talent with industry appropriate backgrounds and personal networks. The goal of this talent is to help mentor startups as they scale and navigate the myriad of issues they will face in growing their business.

Bend’s economic development agency (EDCO) and city leaders (Visit Bend, City of Bend) get it – and have started communicating that Bend welcomes and is friendly to entrepreneurs and startups. Word is spreading and there are lots of people up and down the West Coast who know of and have been to Bend. But it’s easy to get drowned out by the noise from Silicon Valley and other cities in Washington and Oregon. That means that in regional communities like Bend, everyone needs to turn up the volume to consistently sing praises that will not only put the community on the map but also ensure it doesn’t slip.

2. University
Almost every successful tech cluster has a local technical university. This provides a source of technical talent, research, etc. It’s extremely difficult to import enough talent to fuel a rapidly growing tech cluster, so a university is critical to organically generate and retain talent within the region. In particular it’s critical to offer technical degrees that train the talent pool needed to drive the local tech cluster

OSU-Cascades is a new four-year university in Bend that is beginning the build out of its new campus in Bend and offer computer science and user design courses. This effort was over a decade in the making and something that the local community fought hard for.

3. Transportation
Direct flights to the San Francisco Bay Area and other major metro areas (depending on location of the region) are vital to reduce the friction of conducting business, encourage talent to test drive your community, and attract investors and other ecosystem partners to the region.

Bend’s economic development agency (EDCO) has worked very hard to establish direct flights to major West Coast cities including San Francisco, Los Angeles, Seattle, Portland, and Denver. At times this required rallying local business leaders to make advance purchases of flights to ensure enough passenger volume for the airlines.

4. Local Early-Stage Risk Capital
Early stage venture funds are more important than your mother. If this doesn’t exist your regional cluster is dead-on-arrival.  Organize risk-capital in the form of angel funds or venture funds, particularly at the early stage where the largest capital gap exists. This should be a strategic initiative within your state to close the capital gap with in-region capital sources.

Bend is now home to Seven Peaks Ventures and Cascade Angels, both born over the past year in response to the opportunity in the region. The state of Oregon is also making funds available to invest in and support the formation of venture funds within the state.

bvc-winner

Bend Venture Conference Winner

5. Local Entrepreneurial Community Entrepreneurial-driven Events
The local entrepreneurial community has been active in running Startup Weekends, launching the FoundersPad accelerator, running hackathons and Ruby on Rails conferences (Ruby on Ales), building out shared tech space, offering incentives (The Big Bend Theory) for startups to relocate to Bend from the Valley, and building up the state’s largest tech/venture conference, the Bend Venture Conference which is now going on its 11th year. There are many more efforts underway to build upon what has worked and continue the process of evolving and learning.

6. Business Community Support
One of the most difficult things to do is technically the easiest – a dispassionate self-assessment to understand what assets your community has and what you lack.

First, what is your value proposition to a family or business to locate in your region? Recognize that a big part of your job is to remove friction, drive awareness, and amplify the efforts of your local entrepreneurs. Successful entrepreneurs attract other entrepreneurs, so it’s vital to kick start the cycle.

Next, identify your goal. Is it creating a job works program? Stopping brain drain in the region? Attracting and building some key core competency in the region? Ideally your existing talent base and ecosystem naturally support the “core competency magnet” you want to develop.

Finally, put your money where your mouth is – help fund the events and programs in the early years. Once the tech cluster forms, these activities will become self-funding. The ROI won’t be obvious for some early on, but will pay dividends in time.

Regional Cluster Ecosystem

Regional Cluster Ecosystem

Summary: Bend Is a Global Entrepreneurship Experiment
There are about 25,000 economic development agencies in regional markets across the U.S., all trying to expand the number of businesses that create products and services sold outside their region. These regional businesses create primary jobs that lead to the creation of local secondary jobs.

The Bend experiment is a model to consciously engineer an entrepreneurial cluster in a regional market to spur economic development and job creation.

In the past most regional growth strategies have focused on attracting established companies looking to expand or open a new plant. While it may be strategic for the region to recruit some of these established businesses, those deals usually involve huge tax subsidies and typically create a small finite number of jobs. What isn’t part of most regional growth plans is the organic growth of an entrepreneurial tech cluster in the region. If successful, sewing the seeds of entrepreneurship can lead to a more rapid and sustainable job growth for the region.

By engineering a regional tech cluster, we can impact the trajectory of growth in the region and:

  • Slow and even reverse the historical migration of tech talent and capital out of the region/state
  • Locally grow successful tech companies to become amazing primary job creators
  • Recycle the wealth that is created by re-investing in the region versus transferring wealth to Silicon Valley
  • Help local successful entrepreneurial and technical talent stay local – by creating their next startup in the region versus emigrating to Silicon Valley
  • Create a more diversified and healthy economic base that includes tech entrepreneurs

The democratization of entrepreneurship has created a huge opportunity for any region with the right characteristics to create its own sustainable tech cluster. But, as with any true democracy, it won’t happen without the combined participation of the community and desire of entrepreneurs to lead the movement. This is happening in Bend, and I look forward to hearing from others about your own experiments.

Lessons Learned:

  • Regional tech clusters can be engineered if …
    • the region has key attributes and a focused effort from the entrepreneurial and business community
  •  Opportunity exists for economic development in regions where tech clusters can be formed
    • potential to dramatically increase the growth of entrepreneurship and job creation in the region.
  • Entrepreneurs are the path to job creation and growth…
    • attract them, reduce the friction to growth, and do everything possible to cause the wealth created to recycle locally

Listen to the blog post here

Download the podcast here

Early-stage Regional Venture Funds–part 2 of 3 of Bigger in Bend

Dino Vendetti a VC at Bay Partners, moved up to Bend, Oregon on a mission to engineer Bend into a regional technology cluster.  Over the years Dino and I brainstormed about how Lean entrepreneurship would affect regional development.

I visited Bend last year and caught up with his progress.

Mt-Bachelor-Ski-Resort

Today with every city, state and country trying to build out a technology cluster, following Dino’s progress can provide others with a roadmap of what’s worked and what has not.

Here’s Part 2 of Dino’s story…

——-

Tech investing is risky. Success depends on finding startups that have identified acute customer pains in large markets where conditions are ripe for a new entrant. Few entrepreneurs find this scalable and repeatable business model because it’s not easy. However, four critical advances over the past decade (cloud, accelerators, Lean, and Angels) not only changed the math for tech investing but made regional tech clusters possible.

  • The cloud, open-source development tools and web 2.0 as a distribution channel have vastly reduced the amount of capital a startup needs at the early stage when the risk is greatest. (Startups still need capital to scale once they find good product-market fit and a repeatable-scalable business model.)
  • Accelerators, which became mechanisms for focused entrepreneurship mentoring and delivery of best practices to startups. This was valuable to startups in the Valley and has been vital to startups in regions where the ecosystem is less developed.
  • The Lean Movement, led by Steve Blank (and others,) created a set of methodologies that ushered in the era of Evidence Based Entrepreneurship. This has changed the way entrepreneurs think about building their startups and how investors should look at them.
  • Angels & Crowdfunding: Coincident with the capital efficient movement came the current wave of angel investors, this time armed with the ability to collectively fund startups to the point of meaningful value creation on modest amounts of capital. Sites like AngelList have only amplified the collective reach of individual and grouped angel investors.

These four developments, while important to Silicon Valley, are vital to developing regional tech clusters. While the density of Silicon Valley startups can’t be replicated in regions, the barriers of money and resources have disappeared. These changes make entrepreneurship possible anywhere.

What’s Missing Is Early Stage Capital
While the technology gap is closing, what’s still missing in local regions is early stage capital.

Three types of regional venture funds exist today:

  • Regionally located funds, such as Foundry Group in Boulder, are located outside of Silicon Valley or NY but their investments are primarily in the Valley or NY… they are not a regional fund per this discussion.
  • Regional Angel funds that pool investors capital and typically make a one time investment in a startup, sometimes at an early stage but often at a slightly later stage.
  • Late stage large regionally based funds that invest in late stage or mezzanine deals.

Large regionally based early stage funds have mostly failed.  They failed due to:

  1. the dearth of deals in the region that have IPO potential and
  2. most of those funds were also raised and invested prior to the huge capital efficient wave of the past 6-8 years. These regional funds invested in capital-intensive startups that required large initial investments. The result was too much money in too few deals. The inevitable failures then damaged returns.

The Oregon startup scene today looks very different from what it did 10 years ago. Today it’s dominated by capital efficient software, web and mobile startups whereas 10 years ago it was dominated by semiconductor and hardware startups that consumed huge amounts of capital before their first dollar in revenue.

So a regional fund must do three things:

  • focus on early stage investments
  • “right sized” for the exit environment;
    • if it’s too big you won’t be able to intelligently deploy capital;
    • too small and you won’t be able to follow on and protect your investments or make enough investments to ensure you have enough “at bats.”
  • find and focus on the entrepreneurs and deals that want to build scalable startups

We believe that regional funds need to walk a delicate balance…but it doesn’t take huge IPOs to return multiples of capital on a small fund.

Why Valley Rules Don’t Work in Regional Economies
A typical VC fund in Silicon Valley might raise $200 -$400 million.  And over a 10-year life of a fund only one out of five deals will deliver all the returns.  A good return to your investors is 20% per year. That means over 10 years investors expect ~6x return on their investment. This means that those winning deals have to make a ~30x return to provide the venture capital fund that 20% compound return (the 6x).

The Valley strategy is to get as much money to work in the high flying deals that are going to pop….It’s an educated/calculated swing-for-the-fences model and it can work and be extremely lucrative if you can consistently get in those deals.

The problem for a regionally based investor is that there will be a limited number of startups in your region that have a realistic chance at an IPO. The percentage of VC backed startups that go public is very small, so counting on those exits in a regional fund would not be prudent (nice if it happens but don’t build the model to rely on it).

The reality is that the super vast majority of liquidity events are M&A and the majority of those are in the under $100M range. As a result, large multi-hundred million-dollar funds focused on early stage investing in the region can be challenging. There just aren’t enough “right” regional startups to invest in.

Regional Moneyball
Bend playing Moneyball makes a lot of sense. In fact, it’s the only game that investors in a regional cluster can play.  Regional investors need a way of improving their odds of getting base hits and minimize strikeouts.

Playing Moneyball in venture capital means making smaller, smarter bets focused on companies and deals that the big teams, the Silicon Valley heavyweight investors, pass up; because the deals are too far from Silicon Valley, not yet known to them, not in their comfort zone, or not the fad of the month.

Playing Moneyball also means playing with the money you have.  The reality for a regional investor is that you have to match the capital you raise to the deal/exit environment you are in.

Specifically this means that a regional fund should be $10-30M. (With a portfolio of at least 20 investments, or you are at risk of the adverse selection problem.) And the fund should be looking at startups that can provide $20M to $100M exits – almost certainly as M&A deals.

The chart below diagrams our regional fund strategy.

Funds for Regional Markets

The good news for regional investors is that these factors allow you to play Moneyball if (and that’s a big IF) you are investing in entrepreneurs who are living and breathing evidence-based entrepreneurship and who are building scalable startups. This is true whether the company is concept stage or ramping revenue. I’ve found a lot of companies in the region that have found a way to get to some level of revenue traction but haven’t broken out. When you dig in, the reasons are usually easily discoverable and observable.

The Bend Experience
One of the fundamental benefits of being so active in building the FoundersPad accelerator (a 12-week, Lean Startup program focused on customer development) is working with the cohort participants on refining their business models. This experience has provided me a whole new set of pattern matching filters as an investor.

The business model canvas and the customer development process provide investors an incredible opportunity to evaluate how deeply an entrepreneur has engaged with their target customers and, more importantly, what they have learned about the problem-solution space they are going after. This learning and the measurements and metrics that surround it is what evidence based entrepreneurship is all about and what makes it a powerful tool for entrepreneurs, investors and accelerators.

If you are a regional accelerator or investor and would like to talk and compare notes please feel free to email me.

Lessons Learned

  • Regions are missing early-stage capital.
  • Valley-sized VC funds don’t work.
  • Build $10-30M funds.
  • Look for $20-100M exits.
  • Focus on capital efficient, scalable startups and founders

Listen to the blog post here

Download the podcast here

Bigger in Bend – Building a Regional Startup Cluster–part 1 of 3

When Customer Development and the Lean Startup were just a sketch on the napkin, Dino Vendetti, a VC at Bay Partners, was one of the first venture capitalists I shared my ideas with.

Dino and I kept in touch as he moved up to Bend, Oregon on a mission to engineer Bend into a regional technology cluster.  Over the years we brainstormed about how Lean entrepreneurship would affect regional development.

I visited Bend last year and caught up with his progress.

This post and the two that follow highlight what Dino has learned about the characteristics of the startup and investing landscape in a regional market, and what it takes to intentionally engineer a thriving regional tech cluster.

Today, with every city, state and country trying to build out a technology cluster, following Dino’s progress can provide others with a roadmap of what’s worked and what has not. Bend, Oregon is an ideal case study because of its size, location and entrepreneurial characteristics.

Here’s Part 1 of Dino’s story…

———

Let’s get right to the point… I fell in love with Bend, Oregon, once a sleepy logging town, now population 79,000. If you like skiing, hiking, biking, rafting, golfing, camping, fishing, picnicking, rock climbing, and startups – you’d like Bend.1_BalloonsOverBend_2

Before moving to Bend last year, my career took me from engineering development roles at defense contractors in the 80’s to product management and executive marketing roles in companies like Qualcomm in the 90’s, to the world of venture capital at several firms including Bay Partners, Formative Ventures and Vulcan Ventures.

After several visits skiing here, I had become smitten with the “mojo” of Bend – its superb quality of life, recreational opportunities and proximity to the San Francisco Bay Area. The vibe of Bend is appealing, unique and unpretentious given the number of successful business, tech and professional athlete transplants who call it home. It’s home to a small but growing tech community that has been developing over the past decade, and that’s what piqued my interest.

What’s Different
The differences between the Bend, Oregon region and Silicon Valley are obvious. The sheer density of talent, companies, capital and universities that exist in the Valley are second to none. It truly is the epicenter of the startup world and it’s the regional cluster for innovation and entrepreneurship. Working in the Valley, I took for granted the constant and real time networking opportunities, the volume of deals, and the ability to access nearly every corner of the tech industry – no surprise to anyone who has spent any time in the Valley.

However, what I found in Bend was a deeply entrepreneurial community that is leaps and bounds beyond just a destination resort town. Bend fights way above its weight class and is professional scale for its size. Its ability to do so is tied to the deep entrepreneurial DNA that permeates the region (a very similar characteristic to Silicon Valley), originally out of necessity and now out of strategy.

Job creation in Bend is everyone’s business.   People who make the move typically need to start a business to have a job. Bend is the 16th largest metro area in the country for high-tech startup density. Pretty amazing for a town with fewer than 100,000 people.

Startups in Bend
So what types of entrepreneurs and startups exist in Bend?  There’s a concentration around several sectors: software, hardware, medical-technology, aviation, and a specialty of Oregon – craft beer brewing. The chart below shows the clustering of startups around these sectors.

Bend Startup Ecosystem

Bend Startup Ecosystem

In addition to the four major data centers that include Facebook and Apple, Bend currently boasts 95 startups across multiple technologynsectors: 47 software, 26 hardware/semi and 22 med tech related startups. Nearby Portland Oregon (just 160 miles away) is home to over 300 startups; between the two markets, nearly 80 new startups are forming each year.

Silicon Valley Transplants
In addition to local entrepreneurs building startups, I found something else I wasn’t expecting in Bend: a deep pool of talented Valley transplants who’ve made their way to Bend – either during their careers or after. There are retired Fortune 500 CEOs, senior execs from Valley startups and public companies as well as successful entrepreneurs who exited their companies. These smart, successful transplants have gotten involved with the local business community as mentors, advisors, entrepreneurs, or investors.

But the real surprise was learning that for some Bend is a Silicon Valley bedroom community. A daily direct flight on United can have you in your Bay Area office by 8 a.m. Monday. Every week I meet someone new who just moved to Bend and commutes to work for Google, Facebook, Salesforce, Oracle, Marketo, Workday, and on and on….These people are important and useful in the engineering of a tech cluster; as startup coaches, angel investors and advocates for the community. They communicate and pass on the DNA of how Silicon Valley operates and what level of performance is needed to compete on a global scale.

Entrepreneurs in Bend
Within the Bend tech startup community I found three kinds of startups/entrepreneurs:

  • Scalable entrepreneurs similar to those you would find in Silicon Valley (although a smaller concentration exists in Bend). These entrepreneurs want to build a big company. They’re typically Silicon Valley transplants who had enough success and experience to know what they were getting themselves into, what it means to raise capital from investors, what it means to scale a company, and how to engineer an exit.
  • Viable entrepreneurs who think they are building scalable startups but lack either a key element of their business model and/or lack the right team DNA to “go for it..” In this region, these are the majority of new startups I see. They have two limitations, which I help coach to see if they have the capability and desire to become scalable.
    • They go after a market opportunity that’s too limited to result in a truly scalable business (still might be an M&A candidate, but at the lower end of the range).
    • Most teams have a reluctance and willingness to “go for it” when they finally do have a scalable business and have validated the key aspects of their business model. This “small business” mindset is a holdover of how capital starved early stage startups are/were in Oregon. Entrepreneurs (and angel investors) prioritize profitability over growth (this is OK for lifestyle startups, but not for scalable startups where capturing market share and thought leadership is vital).
  • Lifestyle entrepreneurs who are just building a business to make a profit and support their awesome lifestyle (Bend has a lot of these). There is nothing wrong with lifestyle entrepreneurs as they are providing valuable products and services to the local/regional economy, but these do not make for good venture or angel investments under the traditional equity based venture model.

Regional entrepreneurs are at an inherent disadvantage in getting the attention of customers and late stage VCs.  Therefore they need to focus on building the most efficiently scalable business model possible. Without focus, it’s difficult to create enough signal to noise ratio to become relevant in their market segment. The good news is that whether you are an investor or accelerator, if your startup is located in an advantageous regional market (defined below) and if you apply lean methodologies, you can improve your on-base and slugging percentage.

The opportunity and challenge in regional markets is to:

  • Educate the ecosystem about the differences between the three kinds of startups/entrepreneurs
  • Find, nurture and invest in the truly scalable startups and entrepreneurs, as they will be the ones that have the potential to deliver outsized returns

Fixing the Missing Pieces of Infrastructure
The evolution of very capital efficient business models and Lean Startup methodologies has led to easier paths to funding, launching and growing businesses. With a tech cluster developing in Bend, it was clear that there were four missing pieces in its infrastructure.

I decided to fix each of them.

Bend needed a startup accelerator.  While entrepreneurship in Bend was talked about, and everyone read the same blogs, there was no central place founders could get focused and intense coaching and mentorship. So I co-founded the FoundersPad accelerator, a 12-week, Lean Startup program focused on customer development that helps founders develop, refine and grow their business.

Founders Pad

Founders Pad

Bend needed its own venture firm. While Silicon Valley and New York are magnets for great startups, our bet is that awesome startups exist in (or can be attracted to) Oregon and Northern California. So I launched Seven Peaks Ventures with a team of investors that includes some of the region’s most active angel investors. We help Oregon-based startups build and scale their businesses by providing highly relevant mentoring and leveraging our deep network in Silicon Valley and beyond.

Bend needs to attract more entrepreneurs. So I launched The Big Bend Theory with Bruce Cleveland.  We’ll fly founders and their spouses/significant others along with a team member to Bend to meet local startup executives and community leaders and experience the lifestyle. If they choose to relocate in Bend we’ll offer free temporary office space and help get them funded.

Oregon State University’s new Bend campus didn’t have a Computer Science or User Experience design program.  So I helped develop the Computer Science program at Oregon State. (We’re looking for Computer Science professors, so email me if you want to live and teach in Bend!)

Lessons Learned

  • Bend is a bet on a regional tech cluster
  • To build a successful regional cluster, look for an eco-system with:
    • experienced professionals willing to mentor
    • entrepreneurs with the energy and drive to build businesses
    • viable startups under development
  • We are engineering the infrastructure that lacks: accelerator, venture firm, outreach, university and training.
  • It is critical to understand the types of startups and entrepreneurs in your region and for venture funding
  • Seek out the truly scalable startups.

Listen to the blog post here
Download the podcast here

300 Teams in Two Years

This is the start of the third year teaching teams of scientists (professors and their graduate students) in the National Science Foundation Innovation Corps (I-Corps). This month we’ve crossed ~300 teams in the first two years through the program.

I-Corps is the  accelerator that helps scientists bridge the commercialization gap between their research in their labs and wide-scale commercial adoption and use.

I-Corps bridges the gap between public support of basic science and private capital funding of new commercial ventures. It’s a model for a government program that’s gotten the balance between public/private partnerships just right.

While a few of the I-Corps teams are in web/mobile/cloud, most are working on advanced technology projects that don’t make TechCrunch. You’re more likely to see their papers (in material science, robotics, diagnostics, medical devices, computer hardware, etc.) in Science or Nature. The program pays scientists $50,000 to attend the program and takes no equity.

Currently there are 11 U.S. universities teaching the Lean LaunchPad curriculum organized as I-Corps “nodes” across the U.S.  The nodes are now offering their own regional versions of the Lean LaunchPad class under I-Corps.

The NSF I-Corps uses everything we know about building Lean Startups and Evidence-based Entrepreneurship to connect innovation to entrepreneurship. It’s curriculum is built on a framework of business model design, customer development and agile engineering – and its emphasis on evidence, Lessons Learned versus demos, makes it the worlds most advanced accelerator. It’s success is measured not only by the technologies that leave the labs, but how many U.S. scientists and engineers we train as entrepreneurs and how many of them pass on their knowledge to students. I-Corps is our secret weapon to integrate American innovation and entrepreneurship into every U.S. university lab.

Every time I go to Washington and spend time at the National Science Foundation or National Institute of Health I’m reminded why the U.S. leads the world in support of basic and applied science.  It’s not just the money we pour into these programs (~$125 billion/year), but the people who have dedicated themselves to make the world a better place by advancing science and technology for the common good.

I thought it was worth sharing the progress report from the Bay Area (Berkeley, Stanford, UCSF) I-Corps node so you can see what just one of the nodes was accomplishing. Multiply this by the NSF regional nodes across the U.S. and you’ll have a feeling for the scale and breadth of the program.

If you can’t see the presentation above click here

Glad to a part of it.

Lessons Learned

  • The U.S. government has built an accelerator for scientists and engineers
  • It’s scaled across the U.S.
  • The program has taught ~300 teams
  • Balance between public/private partnerships

Listen to the podcast here Download the podcast here
BTW, NCIIA is offering other accelerators and incubators a class to learn how to build their own versions of I-Corps here.

Reinventing Life Science Startups – Evidence-based Entrepreneurship

What if we could increase productivity and stave the capital flight by helping Life Sciences startups build their companies more efficiently?

We’re going to test this hypothesis by teaching a Lean LaunchPad class for Life Sciences and Health Care (therapeutics, diagnostics, devices and digital health) this October at UCSF with a team of veteran venture capitalists.

Part 1 of this post described the issues in the drug discovery. Part 2 covered medical devices and digital health. This post describes what we’re going to do about it.  And why you ought to take this class.

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When I wrote Four Steps to the Epiphany and the Startup Owners Manual, I believed that Life Sciences startups didn’t need Customer Discovery. Heck how hard could it be?  You invent a cure for cancer and then figure out where to put the bags of money. (In fact, for oncology, with a successful clinical trial, this is the case.)

Pivots in life sciences companies

But I’ve learned that’s not how it really works. For the last two and a half years, we’ve taught hundreds of teams how to commercialize their science with a version of the Lean LaunchPad class called the National Science Foundation Innovation Corps.  Quite a few of the teams were building biotech, devices or digital health products.  What we found is that during the class almost all of them pivoted – making substantive changes to one or more of their business model canvas components.

In the real world a big pivot in life sciences far down the road of development is a very bad sign due to huge sunk costs.  But pivoting early, before you raise and spend millions or tens of millions means potential disaster avoided.

Some of these pivots included changing their product/service once the team had a better of understanding of customer needs or changing their position in the value chain (became an OEM supplier to hospital suppliers rather than selling to doctors directly.) Other pivots involved moving from a platform technology to become a product supplier, moving from a therapeutic drug to a diagnostic or moving from a device that required a PMA to one that required a 510(k).

Some of these teams made even more radical changes.  For example when one team found the right customer, they changed the core technology (the basis of their original idea!) used to serve those customers. Another team reordered their device’s feature set based on customer needs.

These findings convinced me that the class could transform how we thought about building life science startups.  But there was one more piece of data that blew me away.

Control versus Experiment – 18% versus 60%
For the last two and a half years, the teams that were part of the National Science Foundation Innovation Corps were those who wanted to learn how to commercialize their science, applied to join the program, fought to get in and went through a grueling three month program.  Other scientists attempting to commercialize their science were free to pursue their startups without having to take the class.

Both of these groups, those who took the Innovation Corps class and those who didn’t, applied for government peer-reviewed funding through the SBIR program. The teams that skipped the class and pursued traditional methods of starting a company had an 18% success rate in receiving SBIR Phase I funding.

The teams that took the Lean Launchpad class  – get ready for this – had a 60% success rate. And yes, while funding does not equal a successful company, it does mean these teams knew something about building a business the other teams did not.

The 3-person teams consisted of Principal Investigators (PI’s), mostly tenured professors (average age of 45,) whose NSF research the project was based on. The PI’s in turn selected one of their graduate students (average age of 30,) as the entrepreneurial lead. The PI and Entrepreneurial Lead were supported by a mentor (average age of 50,) with industry/startup experience.

This was most definitely not the hoodie and flip-flop crowd.

Obviously there’s lots of bias built into the data – those who volunteered might be the better teams, the peer reviewers might be selecting for what we taught, funding is no metric for successful science let alone successful companies, etc.  – but the difference in funding success is over 300%.

The funding criteria for these new ventures wasn’t solely whether they had a innovative technology. It was whether the teams understood how to take that idea/invention/patent and transform it into a company. It was whether after meeting with partners and regulators, they had a plan to deal with the intensifying regulatory environment. It was whether after talking to manufacturing partners and clinicians, they understood how they were going to reduce technology risk. And It was after they talked to patients, providers and payers whether they understood the customer segments to reduce market risk by having found product/market fit.

Scientists and researchers have spent their careers testing hypotheses inside their labs. This class teaches them how to test the critical hypotheses that turn their idea into a business as they deal with the real world of regulation, customers and funding.

So after the team at UCSF said they’d like to prototype a class for Life Sciences, I agreed.

Here’s what we’re going to offer.

The Lean LaunchPad Life Sciences and Health Care class

The goal of the Lean LaunchPad Life Sciences class at UCSF is to teach researchers how to move their technology from an academic lab into the commercial world.UCSF Logo

We’re going to help teams:

  • assess regulatory risk before they design and build
  • gather data essential to customer purchases before doing the science
  • define clinical utility now, before spending millions of dollars
  • identify financing vehicles before you need them

We’ve segmented the class into four cohorts: therapeutics, diagnostics, devices and digital health.  And we recruited a team of world class Venture Capitalists and entrepreneurs to teach and mentor the class including Alan May, Karl Handelsman, Abhas Gupta, and Todd Morrill.

The course is free to UCSF, Berkeley, and Stanford students; $100 for pre-revenue startups; and $300 for industry. – See more here

The syllabus is here.

Class starts Oct 1st and runs through Dec 10th.

Download the all three parts of the Life Science series here.

Listen to the podcast here

Download the podcast here

Reinventing Life Science Startups – Medical Devices and Digital Health

What if we could increase productivity and stave the capital flight by helping Life Sciences startups build their companies more efficiently?

We’re going to test this hypothesis by teaching a Lean LaunchPad class for Life Sciences and Healthcare (therapeutics, diagnostics, devices and digital health) this October at UCSF with a team of veteran venture capitalists.

In this three post series, Part 1 described the challenges Life Science companies face in Therapeutics and Diagnostics. This post describes the issues in Medical Devices and Digital Health.  Part 3 will offer our hypothesis about how to change the dynamics of the Life Sciences industry with a different approach to commercialization of research and innovation.  And why you ought to take this class.

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Medical devices prevent, treat, mitigate, or cure disease by physical, mechanical, or thermal means (in contrast to drugs, which act on the body through pharmacological, metabolic or immunological means). They span they gamut from tongue depressors and bedpans to complex programmable pacemakers and laser surgical devices. They also diagnostic products, test kits, ultrasound products, x-ray machines and medical lasers.

Incremental advances are driven by the existing medical device companies, while truly innovative devices often come from doctors and academia. One would think that designing a medical device would be a simple engineering problem, and startups would be emerging right and left. The truth is that today it’s tough to get a medical device startup funded.

Life Sciences II – Medical Devices

Regulatory Issues
In the U.S. the FDA Center for Devices and Radiological Health (CDRH) regulates medical devices and puts them into three “classes” based on their risks.

Class I devices are low risk and have the least regulatory controls. For example, dental floss, tongue depressors, arm slings, and hand-held surgical instruments are classified as Class I devices. Most Class I devices are exempt Premarket Notification 510(k) (see below.)

Class II devices are higher risk devices and have more regulations to prove the device’s safety and effectiveness. For example, condoms, x-ray systems, gas analyzers, pumps, and surgical drapes are classified as Class II devices.FDA approvals

Manufacturers introducing Class II medical devices must submit what’s called a 510(k) to the FDA. The 510(k) identifies your medical device and compares it to an existing medical device (which the FDA calls a “predicate” device) to demonstrate that your device is substantially equivalent and at least as safe and effective.

Class III devices are generally the highest risk devices and must be approved by the FDA before they are marketed. For example, implantable devices (devices made to replace/support or enhance part of your body) such as defibrillators, pacemakers, artificial hips, knees, and replacement heart valves are classified as Class III devices. Class III medical devices that are high risk or novel devices for which no “predicate device” exist require clinical trials of the medical device a PMA  (Pre-Market Approval).Life Science Decline

  • The FDA is tougher about approving innovative new medical devices. The number of 510(k)s being required to supply additional information has doubled in the last decade.
  • The number of PMA’s that have received a major deficiency letter has also doubled.
  • An FDA delay or clinical challenge is increasingly fatal to Life Science startups, where investors now choose to walk away rather than escalate the effort required to reach approval.

med device pipeline

Business Model Issues

  • Cost pressures are unrelenting in every sector, with pressure on prices and margins continuing to increase.
  • Devices are a five-sided market: patient, physician, provider, payer and regulator. Startups need to understand all sides of the market long before they ever consider selling a product.
  • In the last decade, most device startups took their devices overseas for clinical trials and first getting EU versus FDA approval
  • Recently, the financing of innovation in medical devices has collapsed even further with most Class III devices simply unfundable.
  • Companies must pay a  medical device excise tax of 2.3% on medical device revenues, regardless of profitability delays or cash-flow breakeven.
  • The U.S. government is the leading payer for most of health care, and under ObamaCare the government’s role in reimbursing for medical technology will increase. Yet two-thirds of all requests for reimbursement are denied today, and what gets reimbursed, for how much, and in what timeframe, are big unknowns for new device companies.

Venture Capital Issues

  • Early stage Venture Capital for medical device startups has dried up. The amount of capital being invested in new device companies is at an 11 year low.
  • Because device IPOs are rare, and M&A is much tougher, liquidity for investors is hard to find.
  • Exits have remained within about the same, while the cost and time to exit have doubled.

Life Sciences III – The Rise of Digital Health
Over the last five years a series of applications that fall under the category of “Digital Health” has emerged. Examples of these applications include: remote patient monitoring, analytics/big data (aggregation and analysis of clinical, administrative or economic data), hospital administration (software tools to run a hospital), electronic health records (clinical data capture), and wellness (improve/monitor health of individuals). A good number of these applications are using Smartphones as their platform.digital health flow

Business Model Issues

  • A good percentage of these startups are founded by teams with strong technical experience but without healthcare experience. Yet healthcare has its own unique regulatory and reimbursement issues and business model issues that must be understood
  • Most of these startups are in a multisided market, and many have the same five-sided complexity as medical devices: patient, physician, provider, payer and regulator.  (Some are even more complex in an outpatient / nurse / physical therapy setting.)
  • Reimbursement for digital health interventions is still a work in progress
  • Some startups in this field are actually beginning with Customer Development while others struggle with the classic execution versus search problem

Regulatory Issues

  • Digital Health covers a broad spectrum of products, unless the founders have domain experience startups in this area usually discover the FDA and the 510(k) process later than they should. 

Venture Capital

  • Seed funding is still scarce for Digital Health, but a number of startups (particularly those making physical personal heath tracking devices) are turning to crowdfunding.
  • Moreover, the absence of recent IPOs and public companies benchmarks creates uncertainty for VCs evaluating later investments too

Try Something New
The fact that the status quo for Life Sciences is not working is not a new revelation. Lots of smart people are running experiments in search of ways to commercialize basic research  more efficiently.

Universities have set up translational R&D centers; (basically university/company partnerships to commercialize research).  The National Institute of Health (NIH) is also setting up translational centers through its NCATS program.  Drug companies have tried to take research directly out of university labs by licensing patents, but once inside Pharma’s research labs, these projects get lost in the bureaucracy.  Realizing that this is not optimal, drug companies are trying to incubate projects directly with universities and the researchers who invented the technology, such as the recent Janssen Labs program.

But while these are all great programs, they are likely to fail to deliver on their promise. The assumption that the pursuit of drugs, diagnostics, devices and digital health is all about the execution of the science is in most cases a mistake.

The gap between the development of intriguing but unproven innovations, and the investment to commercialize those innovations is characterized as “the Valley of Death.”valley of death

We believe we need a new model to attract private investment capital to fuel the commercialization of clinical solutions to todays major healthcare problems that is in many ways technology agnostic. We need a “Needs Driven/Business Model Driven” approach to solving the problems facing all  the stakeholders in the vast healthcare system.

We believe we can reduce the technological, regulatory and market risks for early-stage life science and healthcare ventures, and we can do it by teaching founding teams how to build new ventures with Evidence-Based Entrepreneurship.

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Part 3 in the next post will offer our hypothesis how to change the dynamics of the Life Sciences industry with a different approach to commercialization of research and innovation. And why you ought to take this class.

Listen to the post here

Download the post here

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