Why Translational Medicine Will Never be The Same

There have been 2 or 3 courses in my entire education that have changed
the way I think.  This is one of those
.
Hobart Harris Professor and Chief, Division of General Surgery at UCSF

For the past three years the National Science Foundation Innovation Corps has been teaching our nations best scientists how to build a Lean Startup.  Close to 400 teams in robotics, computer science, materials science, geoscience, etc. have learned how to use business models, get out of the building to test their hypotheses and minimum viable product.

However, business models in the Life Sciences are a bit more complicated than those in software, web/mobile or hardware. Startups in the Life Sciences (therapeutics, diagnostics, devices, digital health, etc.) also have to understand the complexities of reimbursement, regulation, intellectual property and clinical trials.

Last fall we prototyped an I-Corps class for life sciences at UCSF with 25 teams. Hobart Harris led one of the teams.

What Hobart learned and how he learned it is why we’re about to launch the I-Corps @ NIH on Oct 6th.

If you can’t see the video click here

Translational medicine will never be the same.

Getting Lean in Education – By Getting Out of the Classroom

This week the National Science Foundation goes Lean on education by providing $1.2 million to educators who want to bring their classroom innovations to a wider audience.

shutterstock_157439453——–

The I-Corps program started when the U.S. National Science Foundation adopted my Lean LaunchPad class. Their goal was to train University scientists and researchers to use Lean Startup methods (business model design, customer development and agile engineering) to commercialize their science. Earlier this month the National Institutes of Health announced I-Corps @ NIH, to help scientists doing medical research take their innovations from the lab-bench to the bedside and accelerate translational medicine.

This week, the NSF is announcing the next step in the I-Corps program– I-Corps for Learning  (I-Corps L).  This version of I-Corps is for STEM educators – anyone  who teaches Science, Technology, Engineering and Math from kindergarten to graduate school, and wants to learn how to bring an innovative teaching strategy, technology, or set of curriculum materials to a wider audience. Following a successful pilot program, the NSF is backing the class with $1.2 million to fund the next 24 teams.

The Problem in the Classroom
A frustration common to both educators and policymakers is how difficult it has been to get new, innovative, education approaches into widespread use in classrooms where they can influence large numbers of students. While the federal government and corporations have dumped a ton of money into STEM education research, a disappointing few of these brave new ideas have made it into practice. These classroom innovations often remain effectively a secret – unknown to most STEM educators or the research community at large.

It turns out that on the whole educators are great innovators but have had a hard time translating their ideas into widespread adoption. What we had was a very slow classroom innovation diffusion rate.  Was there any was to speed this up?

A year ago Don Millard of the National Science Foundation (who in a previous life had been a STEM Educator) approached me with a hypothesis that possibly could solve this problem. Don observed that educators with innovative ideas who actively got out of their classrooms and tested their innovations with other educators/institutions/students had a much better adoption rate.

Up until now there was no formal way to replicate the skills of the educators who successfully evangelized their new concepts. Don’s insight was that the I-Corps model being rolled out for scientists might work equally well for educators/teachers. He pointed out that there was a close analogy between scientists trying to bring product discoveries to market and educators getting learning innovations into broad practice. Don thought that a formal Lean LaunchPad/I-Corps methodology might be exactly what educators needed to understand how their classroom innovations could be used, how to get other educators and institutions to adopt them, and how to articulate their value to potential investors .

Don then recruited Karl Smith from the University of Minnesota to pilot a class of 9 teams made up of STEM educators. Karl recruited a teaching team (Ann McKenna, Chris Swan, Russ Korte, Shawn Jordan, Micah Lande and Bob MacNeal) and Jerry Engel trained them. The team ran their first I-Corps for Learning class earlier this year.

Karl and his teaching team really nailed it. So much so that the NSF is now rolling out I-Corps for Learning on a larger scale.

I-Corps for Learning Details
NSF will provide up to $1.2 million to support 24 teams. The I-Corps L cohort teams will receive additional support — in the form of mentoring and funding — to accelerate innovation in learning that can be successfully scaled, in a sustainable manner.

To be eligible to pursue funding, applicants must have received a prior award from NSF (in a STEM education field relevant to the proposed innovation) that is currently active or that has been active within five years from the date of the proposal submission. Consideration will be given to projects that address K-12, undergraduate, graduate, and postdoctoral research, as well as learning in informal science education environments.

Each team will consist of:

  • The principal investigator (who received the prior award);
  • An entrepreneurial lead (who is committed to investigate the landscape surrounding the innovation); and
  • A mentor (who understands the evidence concerning promise, e.g., from an institutional education-focused center or commercial background that will help inform the efforts)

The outcomes of the pilot projects are expected to be threefold:

  • A clear go/no go decision concerning the viability and effectiveness of the learning-oriented resources/products, practices and services,
  • An implementation “product” and process for potential partners/adopters, and
  • A transition plan to move the effort forward and bring the innovation to scale

Proposals from potential I-Corps L teams will be accepted through September 30, 2014. Class starts January 2015.

Check out the I-Corps for Learning website here.

Lessons Learned

  • The diffusion of STEM classroom innovations is excruciatingly slow
  • The Lean LaunchPad/I-Corps model may accelerate that process
  • I-Corps for Learning is accepting applications

Why Lean May Save Your Life – The I-Corps @ NIH

Today the National Institutes of Health announced they are offering my Lean LaunchPad class (I-Corps @ NIH ) to commercialize Life Science.

There may come a day that one of these teams makes a drug, diagnostic or medical device that saves your life.

—-

Over the last two and a half years the National Science Foundation I-Corps has taught over 300 teams of scientists how to commercialize their technology and how to fail less, increasing their odds for commercial success.

After seeing the process work so well for scientists and engineers in the NSF, we hypothesized that we could increase productivity and stave the capital flight by helping Life Sciences startups build their companies more efficiently.

So last fall we taught 26 life science and health care teams at UCSF in therapeutics, diagnostics and medical devices. 110 researchers and clinicians, and Principal Investigators got out of the lab and hospital, and talked to 2,355 customers, tested 947 hypotheses and invalidated 423 of them. The class had 1,145 engagements with instructors and mentors.NIH I Corps logo

The results from the UCSF Lean LaunchPad Life Science class showed us that the future of commercialization in Life Sciences is Lean – it’s fast, it works and it’s unlike anything else ever done. It’s going to get research from the lab to the bedside cheaper and faster.

Translational Medicine
In life sciences the process of moving commercializing research –moving it from the lab bench to the bedside – is called Translational Medicine.

The traditional model of how to turn scientific discovery into a business has been:
1) make a substantive discovery, 2) write a business plan/grant application, 3) raise funding, 4) execute the plan, 5) reap the financial reward.

For example, in therapeutics the implicit assumption has been that the primary focus of the venture was to validate the biological and clinical hypotheses(i.e. What buttons does this molecule push in target cells and what happens when these buttons are pushed? What biological pathways respond?) and then when these pathways are impacted, why do we believe it will matter to patients and physicians?

We assumed that for commercial hypotheses (clinical utility, who the customer is, data and quality of data, how reimbursement works, what parts of the product are valuable, roles of partners, etc.) if enough knowledge was gathered through proxies or research a positive outcome could be precomputed. And that with sufficient planning successful commercialization was simply an execution problem. This process built a false sense of certainty, in an environment that is fundamentally uncertain.Current tran med

We now know the traditional translational medicine model of commercialization is wrong.

The reality is that as you validate the commercial hypotheses (i.e. clinical utility, customer, quality of data, reimbursement, what parts of the product are valuable, roles of CRO’s, and partners, etc.,) you make substantive changes to one or more parts of your initial business model, and this new data affects your biological and clinical hypotheses.

We believe that a much more efficient commercialization process recognizes that 1) there needs to be a separate, parallel path to validate the commercial hypotheses and 2) the answers to the key commercialization questions are outside the lab and cannot be done by proxies. The key members of the team CEO, CTO, Principal investigator, need to be actively engaged talking to customers, partners, regulators, etc.

outward facing

And that’s just what we’re doing at the National Institutes of Health.

Join the I-Corps @ NIH
Today the National Institutes of Health announced the I-Corps at NIH.

It’s a collaboration with the National Science Foundation (NSF) to develop NIH-specific version of the Innovation-Corps. (Having these two federal research organizations working together is in itself a big deal.)  We’re taking the class we taught at UCSF and creating an even better version for the NIH.  (I’ll open source the syllabus and teaching guide later this year.)

The National Cancer Institute SBIR Development Center, is leading the pilot, with participation from the SBIR & STTR Programs at the National Heart, Lung and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Center for Advancing Translational Sciences.

NIH Uncle Sam smallThe class provides real world, hands-on learning on how to reduce commercialization risk in early stage therapeutics, diagnostics and device ventures. We do this by helping teams rapidly:

  • define clinical utility now, before spending millions of dollars
  • understand the core customers and the sales and marketing process required for initial clinical sales and downstream commercialization
  • assess intellectual property and regulatory risk before they design and build
  • gather data essential to customer partnerships/collaboration/purchases before doing the science
  • identify financing vehicles before you need them

Like my Stanford/Berkeley and NSF classes, the I-Corps @ NIH  is a nine-week course. It’s open to NIH SBIR/STTR Phase 1 grantees.

The class is team based. To participate grantees assemble three-member teams that include:

  • C-Level Corporate Officer: A high-level company executive with decision-making authority;
  • Industry Expert: An individual with a prior business development background in the target industry; and
  • Program Director/Principal Investigator (PD/PI): The assigned PD/PI on the SBIR/STTR Phase I award.

Space is limited to 25 of the best teams with NIH Phase 1 grants. Application are due by August 7th (details are here.)

If you’re attending the BIO Conference join our teaching team (me, Karl Handelsman, Todd Morrill and Alan May) at the NIH Booth Wednesday June 25th at 2pm for more details. Or sign up for the webinar on July 2nd here.

This class takes a village: Michael Weingarten and Andrew Kurtz at the NIH, the teaching team: Karl Handelsman, Todd Morrill and Alan May, Babu DasGupat and Don Millard at the NSF, Erik Lium and Stephanie Marrus at UCSF, Jerry Engel and Abhas Gupta, Errol Arkilic at M34 Capital and our secret supporters; Congressman Dan Lipinski and Tom Kalil and Doug Rand at the OSTP and tons more.

Lessons Learned

  • There needs to be a separate, parallel path to validate the commercial hypotheses
  • The answers to commercialization questions are outside the lab
  • They cannot be done by proxies
  • Commercial validation affects biological and clinical hypotheses

Listen to the blog post here: 
Download the post here

Lessons Learned in Diagnostics

This post is part of our series on the National Science Foundation I-Corps Lean LaunchPad class in Life Science and Health Care at UCSF. Doctors, researchers and Principal Investigators in this class got out of the lab and hospital talked to 2,355 customers, tested 947 hypotheses and invalidated 423 of them. The class had 1,145 engagements with instructors and mentors. (We kept track of all this data by instrumenting the teams with LaunchPad Central software.)

Mira Medicine is one of the 26 teams in the class. The team members are:
  • Pierre-Antoine Gourraud – PhD, MPH UCSF neuroscientist and c0-leader of the MS BioScreen project
  • Jason Crane – PhD UCSF Manager Scientific Software Development
  • Raphaelle Loren – Managing Director – Health Practice at the Innovation Management Institute

Todd Morrill was the diagnostics cohort instructor. Matt Cooper CEO of Carmenta BioSciences was the Mira Medicine team mentor.

Multiple Sclerosis – MS
Multiple Sclerosis – MS – is an immune system disease that attacks the myelin, the fatty sheath that surrounds and protects nerve fibers of the central nervous system (brain, spinal cord, and optic nerve). T-cells, (a type of white blood cell in the immune system,) become sensitized to myelin and cross the blood-brain barrier into the central nervous system (CNS). Once in the CNS, these T-cells injure myelin, and secrete chemicals that damage nerve fibers (axons) and recruit more damaging immune cells to the site of inflammation. multiple sclerosis and therapeutic targets

There are currently ten FDA approved MS medications for use in relapsing forms of MS. None of these drugs is a cure, and no drug is approved to treat the type of MS that shows steady progression at onset. MS disease management decisions are complex and requires a patients neurologist to figure out what drugs to use.

Mira Medicine and Multiple Sclerosis
The team came to class with the thought of commercializing the UCSF Multiple Sclerosis BioScreen Project a Precision Medicine application that integrates a patients medical records with the latest population-based data from hundreds of other Multiple Sclerosis patients, (including their 3D MRI scans,) and using predictive algorithms makes it possible to chart a unique course of treatment for each patient. (Mira Medicine team member Pierre-Antoine Gourraud was the project co-leader.) MS BioScreen

Mira wanted to commercialize the UCSF Multiple Sclerosis Bioscreen project and to add additional neurological diseases which require multiple types of data  (including biomarkers, clinical, and imaging). They wanted to help medical centers and large providers assess disease progression to guide therapeutic decision-making.  Over the course of the class Mira Medicine team spoke to over 80 customers, partners and payers.

Here’s their 2 minute video summary

If you can’t see the video above, click here.

Then reality hit. First, the team found that their Multiple Sclerosis Bioscreen application (which they used as their MVP) was just a “nice-to-have”, not a “must-have”. In fact, the “must have features” were their future predictive algorithms. Next, they found that if their tool can enable a diagnosis, (even without claiming it could) then it was likely that the FDA would require a  510(k) medical device clearance. Then they found to get reimbursed they need a CPT code (and they had to decide whether to code stack – using multiple codes for “one” diagnosis, and thereby getting multiple reimbursements for one test. (The rules have changed so that code stacking is hard or impossible), Or get a new CPT code, or use miscellaneous code.) To get a new CPT and a 510(k) they would have to perform a some sort of clinical study. At a minimum a 1-year prospective study (a study to see if the neurologists using the application had patients with a better outcome then those who didn’t have access to the app). Getting approval to use an existing (aka old) CPT code means showing equivalence to an existing dx process or test, and the requirements are code-specific. Finally, to get access to data sources of other MS patients they would need to have HIPPA Business Associate Agreement.

Watch their Lessons Learned video below and find out how they pivoted and what happened.

If you can’t see the video above click here

Look at their Lesson Learned slides below If you can’t see the presentation above, click here

Lessons Learned

  • Researchers and PI’s come in believing “My science/project/data are so good that people will immediately see the value and be willing to pay for it.  It will “sell itself”.
  • A business is much more than just good science: it is about customers seeing value and being willing to pay and proper validation and reimbursement coding and
  • A successful business is the sum (and integration!) of all the parts of the business model canvas.
    • It includes reimbursement, regulation, IP, validation, channel access, etc.

Listen to the blog post here

Download the podcast here

Lessons Learned in Therapeutics

This post is part of our series on the National Science Foundation I-Corps Lean LaunchPad class in Life Science and Health Care at UCSF. Doctors, researchers and Principal Investigators in this class got out of the lab and hospital talked to 2,355 customers, tested 947 hypotheses and invalidated 423 of them. The class had 1,145 engagements with instructors and mentors. (We kept track of all this data by instrumenting the teams with LaunchPad Central software.)

We are redefining how translational medicine is practiced.

Traditional view of translational medicineWe’ve learned that translational medicine is not just about the science.

More on this in future blog posts.

Lean view of translational medicine

Vitruvian Therapeutics is one of the 26 teams in the class. The team members are:
  • Dr. Hobart Harris  Chief of  General Surgery, Vice-Chair of the Department of Surgery, and a Professor of Surgery at  UCSF.
  • Dr. David Young,  Professor of Plastic Surgery at UCSF. His area of expertise includes wound healing, microsurgery, and reconstruction after burns and trauma. 
  • Cindy Chang is a Enzymologist investigating novel enzymes involved in biofuel and chemical synthesis in microbes at LS9

Karl Handelsman was the therapeutics cohort instructor. Julie Cherrington CEO of Pathway Therapeutics was the team mentor.

Vitruvian Therapeutics is trying to solve the Incisional hernia problem. An incisional hernia happens in open abdominal surgery when the area of the wound doesnt heal properly and bulges outward. This requires a second operation to fix the hernia.Ventral Herniaincisional hernia

Hobart Harris’s insight was what was needed wasn’t one more new surgical technique or device to repair the hernias, but something to prevent the hernia from occurring in the first place. Vitruvian Therapeutics first product, MyoSeal, does just that. It promotes wound repair via biocompatible microparticles plus a fibrin tissue sealant. So far in 300 rats it’s been shown to prevent incisional hernias through enhanced wound healing.

Here’s their 2 minute video summary

If you can’t see the video above, click here.

Two weeks into the class and interviews with 14 of their potential customers (surgeons) reality intruded on their vision of how the world should work. We happened to catch that moment in class in this 90 second clip.

Watch  and find out how talking to just the first 14 customers in the Lean LaunchPad class saved Hobart Harris and the Vitruvian Therapeutics team years.

If you can’t see the clip above click here.

The Vitruvian Therapeutics Lessons Learned Presentation is a real-eyeopener. Given that this product could solve the incisional hernia problem, Hobart and his team naturally assumed that insurance companies would embrace this and their fellow surgeons viewed the problem as they did and would leap at using the product. Boy were they in for a surprise. After talking to 74 surgeons, insurance companies and partners appeared that no one – insurance companies or surgeons – owned the problem. Listen to their conclusions 8-weeks after the first video.

Watch the video and find out how they pivoted and what happened.

Don’t miss Karl Handelsman comments on their Investment Readiness Level at the end. Vitruvian is a good example of a great early stage therapeutics idea with animal data missing and many key components of the business model still needed to verify.

If you can’t see the video above click here

Look at their Lesson Learned slides below

If you can’t see the presentation above, click here

Market Type
During the class the Vitruvian Therapeutics class struggled with the classic question of visionaries: are we creating a New Market (one which doesn’t exist and has no customers)? In Vitruvian’s case preventive measures to stop incisional hernias before they happen.  Or should we position our product as one that’s Resegmenting an Existing Market? i.e. reducing leakage rates.  Or is there a way to get proof that the vision of the New Market is the correct path.

When Hobart Harris of Viturvian asked, “… what if you’re a visionary, and no one but you sees the right solution to a problem” we had a great in-class dialog. Karl Handelsman‘s comments at 3:15 and 4:16 and Allan May at 4:35 were incredibly valuable. See the video below for the dialog.

If you can’t see the video above, click here

Further Reading

Lessons Learned

  • Principal Investigators, scientists and engineers can’t figure out commercialization sitting in their labs
  • You can’t outsource commercialization to a proxy (consultants, market researchers, etc.)
  • Experiential Learning is integral to commercialization
  • You may be the smartest person in your lab, but your are not smarter than the collective intelligence of your potential customers, partners, payers and regulators

Listen to the blog post here

Download the podcast here

Lessons Learned in Medical Devices

This post is part of our series on the National Science Foundation I-Corps Lean LaunchPad class in Life Science and Health Care at UCSF. Doctors, researchers and Principal Investigators in this class got out of the lab and hospital talked to 2,355 customers, tested 947 hypotheses and invalidated 423 of them.  The class had 1,145 engagements with instructors and mentors. (We kept track of all this data by instrumenting the teams with LaunchPad Central software.)

We are redefining how translational medicine is practiced. It’s Lean, it’s fast, it works and it’s unlike anything else ever done.

—–

Sometimes teams win when they fail.

Knox Medical Devices was building a Spacer which contained a remote monitoring device to allow for intervention for children with Asthma . (A Spacer is a tube between a container of Asthma medicine (in an inhaler) and a patient’s mouth.The tube turns the Asthma medicine into an aerosol.)Asthma

Knox’s spacer had sensors for basic spirometry measurements (the amount of air and how fast it’s inhaled and exhaled) to see how well the lung is working. It also had a Nitrous Oxide sensor to provide data on whether the lungs airways are inflamed, an inhaler attachment and a GPS tracking device.

Knox SpacerThe Spacer hardware was paired with data analysis software for tracking multiple facets of asthma patients.

The Knox team members are:

Allan May founder of Life Science Angels was the Medical Device cohort instructor. Alex DiNello CEO at Relievant Medsystems was their mentor.

The Knox team was a great mix of hands-on device engineers and business development. They used agile engineering perfectly to continually test variants of their Minimum Viable Product (MVP’s) in front of customers often and early to get immediate feedback.

Knox was relentless about understanding whether their device was a business or whether it was technology in search of a market. In 10 weeks they had face-to-face meetings with 117 customers, tested 33 hypotheses, invalidated 19 of them and 53 instructor and mentor interactions.

Here’s Knox Medical’s 2 minute video summary

If you can’t see the video above, click here

Knox was a great example of having a technology in search of a customer. The initial hypothesis of who would pay for the device – parents of children with asthma – was wrong and resulted in Knox’s first pivot in week 4. By week 6 they had discovered that; 1) Peak Flow Meters are not as heavily prescribed as they thought, 2) Insurance company reimbursement is necessary for anything upwards of $15, 3) Nitrous Oxide testing isn’t currently used to measure asthma conditions.

After the pivot they the found that the most likely users of their device would be low income Asthma patients who are treated at Asthma clinics funded by federal, state or county dollars. These clinics reduce hospitalization but Insurers weren’t paying to cover clinic costs nor would they cover the use of the Knox device. The irony was that those who most needed the Knox device were those who could least afford it and wouldn’t be able get it.

Watch their Lesson Learned presentation below. Listen to the comments from Allan May the Device instructor at the end.

If you can’t see the video above, click here

In the end Knox, like a lot of startups in Life Science and Health Care, discovered that they had a multi-sided market.  They realized late in the class the patients (and their families) were not their payers – their payers were the insurance companies (and the patients were the users.)  If they didn’t have a compelling value proposition for the insurers (cost savings, increased revenue, etc.) it didn’t matter how great the technology was or how much the patients would benefit.

The Knox Medical Device presentation slides are below. Don’t miss the evolution of their business model canvas in the appendix. It’s a film strip of the entrepreneurial process in action.

If you can’t see the slides above, click here

Knox is a great example of how the Lean LaunchPad allows teams to continually test hypotheses and fail fast and inexpensively. They learned a ton. And saved millions.

Lessons Learned

  • In medical devices, understanding reimbursement, regulation and IP is critical
  • Sometimes teams win when they fail
Download the podcast here

Lessons Learned in Digital Health

This post is part of our series on the National Science Foundation I-Corps Lean LaunchPad class in Life Science and Health Care at UCSF.

Our Lean LaunchPad for Life Science class talked to 2,355 customers, tested 947 hypotheses and invalidated 423 of them.  They had 1,145 engagements with instructors and mentors. (We kept track of all this data by instrumenting the teams with LaunchPad Central software.)

This post is one of a series of the “Lessons Learned” presentations and videos from our class.

Sometimes a startup results from a technical innovation. Or from a change in regulation, declining costs, changes in consumers needs or an insight about customer needs. Resultcare, one of the 26 teams in the class started when a resident in clinical medicine at UCSF watched her mother die of breast cancer and her husband get critically injured.

The team members are:

  • Dr. Mima Geere  Clinical Medicine at UCSF.
  • Dr. Arman Jahangiri HHMI medical fellow at UCSF, Department of Neurological Surgery
  • Dr. Brandi Castro in Neuroscience at UCSF
  • Mitchell Geere product design
  • Kristen Bova MBA, MHS
  • Nima Anari PhD in Data Science

Abhas Gupta was the Digital Health cohort instructor. Richard Caro was their mentor.

ResultCare is a mobile app that helps physicians take the guesswork out of medicine. It enables physicians to practice precision medicine while reducing costs.precision medicine

Here’s Resultcare’s 2 minute video summary

If you can’t see the video above, click here.

Watch their Lesson Learned presentation below. The first few minutes of the talk is quite personal and describes the experiences that motivated Dr. Geere to address this problem.

If you can’t see the video above, click here

The Resultcare presentation slides are below.

If you can’t see the presentation above, click here

Listen to the blog post here

Download the podcast here

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