Lessons for “Lean Start-up” / “Evidence based Entrepreneurs” in Lifesciences: 2

Reducing development & reimbursement risk,

whilst achieving pre-approval sales.

Intercytex Ltd

Paul Kemp, CEO

I spoke recently with Paul Kemp, CEO of cellular therapy company Intercytex, regarding approaches to reducing time, cost and risk in product development and reimbursement.  Including their “Progressive Translation” approach and forthcoming Cell2therapy^TM “Contract Translation Service”.

Development & pre-approval sales

Paul began by outlining two long standing routes to getting product to the patient (in UK) before a formal MHRA marketing license:

·    “Specials” – this applies to any type of medicinal product but has to be a bone fide request from a clinician and can only be used if a licensed alternative is not available, the product can be exported if it is legal to supply unlicensed products to patients in the receiving country.

·    “Hospital Exemption” – for ATMP (i.e. Regen Med & gene therapy) only, and applies even if a licensed alternative is available, provided that the physician determines this is better.  But is hospital use only, and cannot be routine, nor exported. .

He then mentioned the work of Brian Salter, who believes that the development of Stem Cell therapeutic products is predominantly;

·    Science led in The West; so that patients/doctors etc. have to wait until a company delivers a licensed therapy.   It’s a very linear approach, risky and time consuming.

·    Demand led in The East; with an individual patient focus & based upon clinical experience and medical innovation, and is a circular (iterative) processes. (C.f. transplantation in the UK). Hence it’s quicker and less risky.  However, this approach cannot achieve broad application until a marketing license is obtained.

Intercytex have developed a "Progressive Translation” approach, which combines the best of both worlds. This arose during their development of their fibroblast preparation based wrinkle therapy.  They followed the classic linear approach and completed Phase two trials.  Unfortunately the Fibroblast prep was not sufficiently efficacious using the trial’s protocol to make it economically viable.  Part of problem was that in phase 2b one uses “Dose ranging” to determine optimal doses ready for  phase 3.  However, as Paul explained, for cells (cell based products) this is not that relevant – more important is the overall protocol such as number of doses over what time i.e. “Protocol ranging” - and phase 2 approvals don’t allow this!

They were in the classic trap of being locked into a product that does not work (well enough), and nowhere to go – so abandon?  Not in their case: they realised some of their trial physicians were using Fibroblast preps under the Specials procedure to test out as a therapy for Epidermolysis bullosa and scar contractures.  So they pivoted to these applications, and are taking a “time-out” from phase 2 trials.  The clinicians are treating patients under Specials, with “very promising results”, and the information gained is helping to develop a better protocol for use in later trials.  What’s more, clinicians are sometimes able to obtain reimbursement on a “Named Patient” basis.  And all of this is within existing legislation.

The one thing to be particularly careful about, Paul indicated, is that a company cannot promote a Special product nor make any efficacy claims, so that care needs to be taken in getting physicians involved.  Intercytex are looking at the optimum way to interact with clinicians with the current legislative framework

They are establishing Cell2therapy^TM a “Contract Translation Service", in collaboration with UHSM at Wythenshawe in order to provide this to third parties.

The other approach Intercytex are taking to de-risk development is “to build change into the product from the start”.   The issue is once you’ve defined and agreed your product with the regulator, you are locked in.  So subsequent changes need a large effort, to effectively go back to the start.  

Paul’s approach now, is to discuss with the regulator, “testing the water”, to define the minimum aspects necessary to achieve the expected function of the product (effectively an MVP), thereby providing sufficient leeway for later stage product modifications.  This allows process and even product changes, provided “comparability” can be determined.  

He also mentioned, that once in phase 3, there are the more widely know approaches to expediting registration/sales, such as conditional licenses, orphan status, breakthrough product designation….”the national competent authorities around the world have appreciated that the current standard clinical trial process provides a huge burden to a therapy developer, and are working to improve the situation without compromising patient safety.”

Reimbursement games

A further benefit of the specials etc. approach (achieving pre-approval sales), is that “you develop some degree of market pricing”, along with evidence for cost: benefit, which then aids in reimbursement discussions. It’s also the case that patients can pay for specials, hospital exemptions etc. themselves, although co-payment is not possible (in UK).  This helps to de-risks reimbursement negotiations. 

“we are learning the reimbursement games”!

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 This post is part of an occasional series exploring lessons for risk, time and cost reduction, and the application of Lean Start-up techniques and Evidence based Entrepreneurialism to Lifescience based start-up companies.  Ideas explored during The Science of Entrepreneurship event, and practiced at Next Business Generation, Nottingham.

Lessons for “Lean Start-up” / “Evidence based Entrepreneurs” in Lifesciences

Tightly define both your product/service offering

 and the customer’s problem that it solves

Imagen Biotech

Rod Benson COO

(10/3/14)

I spoke recently with Rod Benson of Imagen Biotech, which he founded in 2007, with the proposition of being a High Content Screening CRO for Pharma Industry.  As you may recall, around this time HCS was the broadly seen as the new panacea for all the sector’s R&D ills, and many expected that it would fulfil the promise of restoring innovation and productivity to Big Pharma R&D (as had been thought for HTS previously!).  So this seemed like a great idea. 

Rod’s lesson for “Evidence Based Entrepreneurs” (lean start-up) is that a specific tight definition of the problem to be solved and solution to that problem (that you are offering), gives rise to clear and actionable interest, whereas broad multivariate offerings are deceptively well received (false positives), but give little real learning, and do not translate to sales.

Initial discussions with a number of Pharma’s, proposing a service offering based on a broad panel of many different assays within a HCS platform, gave lots of positive indications of interest.  So a business plan was put together, a working bank overdraft of 50K obtained based on a letter of intent from AstraZeneca. Early on they obtained a grant, several small studies and two larger contracts which made the company look as if it was following a healthy start-up trajectory. This allowed them to write an upbeat business plan to raise 400K to upgrade their equipment.  However, things started to “go off the rails” after this 400K investment in 2011.  Sales leads failed to materialize and this continued to grow worse during 2012 resulting in a year on year decrease in turnover. Whilst some of this is likely due to the tough economic conditions and the patent cliff, Rod contends that although the broad service offering created early interest, it leads to a woolly sales message….

“What companies prefer to be told is how they can solve a specific problem [assuming this is so] and that you have a specific answer that will solve this for them”.  

With a cash crisis looming at the end of 2012, they looked around to see what other opportunities where available with the now more developed technology base. Existing collaborative work, with The University of Manchester, showed good clear results in testing for cell death within glioblastoma stem cell cancer samples.  And their own drug discovery program around phenotypic screening of natural product libraries was showing promise. After an initial aborted fundraising attempt and  careful financial modelling of the personalized medicine idea, they concluded that development of a business around personalized chemotherapy had all the “upside” of a blockbuster drug but none of the downside of trying to get a new entity through first phase clinical trials.  Armed with this they wrote a much more focussed plan based solely on personalized chemotherapy and Pivoted from a broad general service offering to a specific one focused on offering a chemosensitivity assay to the NHS and private hospital sector.  With this and a new CEO, they were able to raise investment of ~£1M from a HNW syndicate, which in Rod’s words “happened only just in time”!  Imagen Biotech is now developing this new service platform with a great deal of specific interest from potential customers. 

Could this pivot have happened much earlier?  Actually, not that much.  Neither the screens themselves nor the enabling vision-hardware & software were sufficiently developed at the start, for this possibility to exit even perceptually. 

His conclusion, to reiterate, is that a specific tight definition of the problem to be solved and solution to that problem (that you are offering), gives rise to clear and actionable interest, whereas broad multivariate offerings are deceptively well received (false positives), but give little real learning, and do not translate to sales.

Rod also observed that “Service businesses just don’t [normally] give enough uplift for VCs”.

This post is part of an occasional series exploring lessons for risk, time and cost reduction, and the application of Lean Start-up techniques and Evidence based Entrepreneurialism to Lifescience based start-up companies.  Ideas that will be explored in the forthcoming The Science of Entrepreneurship event, and are practiced at Next Business Generation, Nottingham.

CrowdCure: Combining Philanthropy with Upside Potential

Is CrowdCure the answer to the tricky dilemma of true crowdfunding for biotech start-ups & drug discovery?   To find out I spoke with Charles Groome, founder of the soon to be launched CrowdCure.

Charles is a Neuroscience graduate of UCL, who started his career trading pharmaceutical stocks at financial services firm Knight Capital, and then left to raise a $25 million venture capital fund to invest in early-stage biotech companies focused on longevity. Despite raising commitments for a third of this sum, he failed to secure sufficient funds overall. He also worked to raise seed capital for one of the companies he planned to eventually back, and so encountered most of the life science VCs on both sides of the Atlantic. His conclusion that VC risk and time profiles are inappropriate for drug discovery, is shared by many of us (e.g. see Funds & Fundability).  The success of Kickstarter et al drew his attention, indicating the success of the crowdfunding approach to specific projects, with its philanthropic nature and ability to pool small sums of money from large numbers of people.

He’s not alone in that of course, as many have considered this approach.  The issue is generally how to marry long timescales & high risk with investment to obtain a return.  CrowdCure’s solution is first to tap into philanthropy in the crowd, with the spice of a potential upside if a particular project is eventually successful.  And secondly, to recognise any success as early as possible, by sharing collaborative revenues, as well as acquisition proceeds.

How does it work?  CrowdCure establishes a “Special Purpose Vehicle” company for each project. 

As part of a “Research Financing Agreement” the SPV exclusively licenses Project IP from the Biotech Company seeking funding, and then sub-licenses it back to the Company, who continue to control asset development. All future Project revenue streams from licensing are transferred to the SPV. The SPV has two lines of shares; voting and non-voting. The voting shares are held in trust and the non-voting shares are distributed as “Research Income Rights”^TM (RIR) to the crowdfunders (via the online portal) and to the Biotech company. This is done in line with a third-party attained valuation.

CrowdCure Ltd receives a commission as a % of funds raised, and “Research Drivers LLP”, the SPV trustee shareholder and administration entity (which licenses the whole structure), receives a small % of any future SPV income pre-distribution. CrowdCure Ltd is an Appointed Representative of an FCA Authorised Firm.

If the biopharma asset develops to the point of commercial value, Big Pharma can either sub-license it from the SPV or acquire the SPV outright.

A SPV approach was used a lot in the early days of US biotech, and seems similar to recent approaches taken by Versant and Atlas Ventures (Fierce Biotech articles).  Charles is an advocate, pointing out the benefit for a biotech being able to raise separate funds for each of a portfolio of single projects, and subsequently selling on the projects when new skill sets are needed.  Whilst recognising that the crowd are more interested in backing Projects with a social cause (e.g. cure Alzheimer's) than investing in risky and obscurely named Biotech companies.  Becoming a “Cure Pioneer” recognises their contribution, and motivates along with the chance for upside.  The RIR approach seems to be novel though.

So what are they looking for?  Its early stage pharmaceutical opportunities, pre-clinical, with a validated/proven target being required, and hit discovery welcomed.  They will also check it out thoroughly, conducting VC’esque Due Diligence on the science & data, requiring a sound project plan & budget, and checking out the team & company background, IP etc.  It also has to fit with their portfolio, which will diversify, rarely addressing already invested areas.

CrowdCure sees itself as a global portal “Crowdfunding for Life”, acting as a “Branded Venture Broker”, enabling sophisticated investors, High Net Worths and “qualified investors” (anyone who can answer six questions on their site) to all contribute.  They are planning to be the first UK & USA operating portal.  Appropriate regulatory requirements are in place in UK, and nearing completion in USA.  With launch scheduled for late July, these are exciting times.

They have big plans – by year 5, to raise over £100m and progress at least one project into clinical trials. 

So for the Biotech, an alternative approach to get that early capital so elusive at present, and

for VCs, perhaps a source of future de-risked opportunities, risk-sharing or co-investment?

For the investor, this is high risk investing, and Charles is keen to stress that.  None the less, if you want to do some good in the world, and would appreciate a possible upside as well, this could be worth a look.  As Charles points out, you too can become a “Cure Pioneer”…….

Lifescience / Healthcare Start-up Evolution?

Lean Start-up, Accelerators and Business Model Canvas in Lifescience/Healthcare?

Can the Lifesciences / Healthcare sector’s business start-ups learn from the experience and techniques of the Tech / Digital sectors? I’m thinking particularly of speed to market, and success rates.  If so it this could well boost investment into this sectors start-ups!

As a starting point to investigating this further I’m reviewing/benchmarking the use of three “techniques” within Lifescience/healthcare sector, and would like to ask or your help with this, via three queries.  The aforementioned “techniques” are listed below along with links to brief Linked-In polls.  Many thanks in anticipation of your help - I will of course freely publish the results on my Blog!

1.      The rise of the Tech Accelerators such as the original Y-Combinator and TechStars, and a number of followers in USA & Europe, are a testament to the success of the Accelerator approach (reviewed by NESTA report Start Up Factories, and utilising community based approach elaborated by Brad Feld www.startuprev.com).  Until the recent Health Wildcatters launch in Dallas and Harvard announcement for funding of a new healthcare accelerator, there appeared to be none active in our sector. Are you aware of any others existing or planned?

Poll: http://linkd.in/12wJRSl

Related are the “Lean Start-up” , movement developed by Eric Ries (theleanstartup.com), and the Business Model Generation techniques of Alexander Osterwalder and Yves Pigneur (www.businessmodelgeneration.com.  In particular techniques such as Minimum Viable Product and Business Model Canvascanvas.  These are reviewed in brief article by Steve Blank, Why the Lean Start-Up Changes Everything (hbr.org/2013/05/why-the-lean-start-up-changes-everything/ar/1).

 Are you aware of these techniques being used in Lifesciences / Healthcare sub-sectors?

2.      Lean Start-up                              Poll: http://linkd.in/17oPuHR

3.      Business Model Canvas             Poll: http://linkd.in/17oPl7b

I look forward to receiving your input.

Many thanks

Nick
nickpope@biospring.co.uk

NHS Open for Business ?

East Midlands AHSN

There will soon be a new "kid on the Block", with the aim of opening the NHS for business!

I thought readers may well be interested to hear of these new organisation that will make the NHS much more user friendly for business - be it research, trials, or marketing!

So here’s a “heads up” on the forthcoming launch of one - the East Midlands AHSN.

EMAHSN’s vision is “The transformation of patient access, experience and outcomes...through innovation and enterprise working” (www.emahsn.ac.uk provides a general overview). Working with Industry, and facilitating such, is central to their approach.  They aim to be a one stop shop for industry interaction with the NHS in EM, for all purposes: be that adoption of new products, user testing / product development, clinical trials, or clinical research; or indeed assisting NHS derived innovations to be commercialised and the promotion of clinical needs  to industry to expedite the development of new interventions.  The organisation will become ‘live’ April 2013.

A specialist industry support unit will facilitate the one-stop-shop for industry, assisted by a web-portal, and a small seed funding activity will help new innovative ideas get started.  A series of events to highlight the NHS’ clinical “Priority Needs” and enabling networking between industry and clinicians is being planned, and regular Networking events will follow, as will attendance at Biotech/Pharma/MedTech sector events.

personally, I'm proud to be involvement as the Commercial Adviser for this industry facing component, and as such I would be delighted to provide more information on request ? 

Nick

nickpope@biospring.co.uk

Open Innovation (in Biotech/Pharma)

BIA breakfast meeting 28/11/12, BioCity, Nottingham

One of a series of  BIA Breakfast events around the UK; Chaired by BIA CEO Steve Bates, with panel members Clare O’Neil, Original Ventures and Nick Pope, BioSpring Ltd.

Supporting material for Nick’s contribution:

Definitions

Innovation is “using a novel approach to satisfy a real market need”, and so inherently requires commercialisation. OI tends to be thought of as the ideation and research end only, whereas the later stages are also important.

Open can mean one, or both, of:

1. Collaborative v’s competitive, trusting, operating with a “Win Win” ethos, or

2. Open to outside ideas (Big Pharma)

Open Innovation is generally more open, trusting, with networking at its core, and with True “win-win” working (not just pretending so!). Hence it needs personal and organisational alignment to succeed (see Success Factors).

On the surface, it’s fairly similar to what small co.’s often have done anyway, but to a much greater extent, enabled by the speed, ease and global reach of communications the digital age makes possible. Ownership of resources is no longer key, rather it’s the networks to be able to access the resources that is! (e.g. drug molecule screening in silico, now run in the cloud. Computers are not important, its algorithms & molecules that are).

• Ideas, IP, Knowledge and knowhow can easily flow!

Open Innovation brings a New Paradigm and New ways of managing innovation:

• fail quick and learn fast
• innovation ecosystems rather than Assets,
• “connectors” (access points) as well as the research itself.
• An easy way to tap into other skill-sets when you need them.

Examples

There is a Spectrum of OI,

a.   Open access journals (e.g. nature’s web journal), Structural  Genomics Consortium making structure data freely available & GSK giving access to its trials data,

b.   Easy Access IP initiative, where Bristol, UCL & Glasgow Universities have opened their “difficult to commercialised” IP to everyone,

c.   Specific company initiatives using portals or agreements to

1. access new molecules (Lilly’s OIDD portal, or Unilever) or
2. new applications for (old / failed) molecules (AZ/MRC deal, & NCATS initiative),

d.   Sponsored challenges with funds and a problem, often posted on third party portals such as www.innoget.com, www.innocentive.com, www.kaggle.com

e.   True crowdsourced e.g. www.Zooniverse.org & mechanical turk (https://www.mturk.com/mturk/welcome).

Then there is Crowdfunding e.g.

1. Seedrs (UKFSA regulated) www.seedrs.com
2. Wiseed (F) www.wiseed.fr/; 

“First biotech seed crowdfunding” – Anabio (www.antabio.com/en)

3. BIA Citizens Innovation Fund (citizens-innovation-funds-report/)

And where Big Pharma are opening up to early stage science through a variety of approaches, including incubatorse.g. GSK & Stevenage BioScience Catalyst, and Merck & not-for-profit Calibr.

IP

Same requirements as usual, but more pragmatic – they are only applied once a project gets to commercial/competitive phase. Not just for the sake of it. But, put clear agreements in place from the start, to deal with IP when it becomes relevant.

Avoid joint IP (it will be if no agreement is in place from start), as in the UK (not USA) jointly owned IP requires All owners to agree to the exploitation by any of the owners! (unless explicitly agreed otherwise).  This can cause big problems if not dealt with in advance.

Success factors

Clear understanding, alignment and agreement by all parties from the start.

·    Personal & organisational alignment – the “soft aspects” that often derail collaborations! - lessons can be learned from other industries, and techniques borrowed (networkedpharma).

·    A well-structured agreement Formal agreement embodying all of this, and incl.

·        Clear Mutual understanding of what each party wants out of it – objectives

·        Clear IP ownership and commercial exploitation rights agreement

·        Agreement project management structure and process aimed at Effective monitoring and management of projects

e.g. Lilly’s web based OI portal for sourcing new molecules establishes a master agreement with each new University/institution as a faculty member wants to submit ideas.  This is then in place for all subsequent members from same institution.

·    High level champion in each organisation

·    Clear open communications (co-location helps)

·    Focused approach

·    Willingness and system to “fail fast, learn quick”

·    Network with multiple connections

Sources:

1. NetworkedPharma Funds & Fundability workshop June 2012 (report available Mid December).
2. Above hyperlinks.

BioSpring Ltd is a member of Networked Pharma Partnership, a not for profit organisation dedicated to assisting development of a new paradigm for drug discover & development

Networked Pharma Partnership; Building Innovative Networks in Drug Discovery & Development

A series of workshops are being run to bringing together all stake-holders (Corporate Pharmas, SMEs, CROs, Universities, VCs, CVCs, Research Councils, Charities, Regulators & Government bodies etc.) to help formulate the new business model(s) for the future success of the industry.

Follow us:

Twitter @NWkPharma,      #NWkRx

Funding for Innovative Drug Discovery: UK 2012

Networked Pharma – Finance (NWkRx F8)

 Networked Pharma’s Workshop

Funds and Fundability, 28^th June 2012

Executive Summary

Networked Pharma’s “Funds and Fundability” workshop examined the evolving funding ecosystem (equity, collaboration & grant) and the future role of open innovation (OI) for early stage drug discovery.

Key opinion leaders were joined by 60 participants from diverse stakeholder backgrounds, for presentations and facilitated discussions (report available on request).  Workshop website.

Key Findings

A.  Investor consensus surprisingly positive for biotech/pharma sector.

o There are hidden / ‘below the radar’ fundraisings occurring,

o Although the old investment model is dead in UK, and the public markets closed, there is now a new model of a single large investment sufficient to go all the way to achieve an exit by trade sale.

o Funds are emerging with “Patient” Capital (i.e. they are prepared to wait long enough for value creation to occur).  However, more are needed.

B.   UK is good at producing lean companies with 1 or 2 products that are sold-off too soon for early exit and financial return:

“You Brits are very good a creating ‘Veal’ ready for slaughter”

Participant quoting a USA colleague                           

Rather than being prepared to wait and build a self-sufficient multi-product company and so realise the full potential value. 

“We need the fodder to build ‘Beef’”     Serial biotech entrepreneur

More Patient capital is needed for this and probably the public markets.

“Are we prepared to be patient?”   VC

Sector needs

1.      A new / “better” way to capture information on fundraisings.  Many current investments are “under the radar” as different types of investor are now involved, and there is no need for publicity. This will enable us all to know what is actually happening and to recognise successes.

2.      A better way to recognise our UK pharma/biotech company successes, and new measures to assist with this (not just financial).

3.      Support for entrepreneurs to decide which of the funding sources to approach: i.e. Fill the information gap between funders (of all types including government/research bodies) and those looking for funding

1. Which of the three “silos” of equity investor’s to approach, and who to contact therein? The three silos rarely interact: 1. VC/CVC, 2. Angels/regional funds, & 3. Public-listed funds.
2. Which grant funding and other non-equity sources are applicable to given types/stages of projects/companies, and who to contact?

4.      More equity funds that straddle the three silos.

5.      The creation of some biotech/pharma Sector Champions (“Beef”) in UK, and more investors prepared to be “patient” (prepared to wait 10+ years to develop full value and achieve such champions).

6.      Engagement of the public markets with biotech.

7.      More specific information and better information sources on OI & Crowdsourcing within Drug discovery, and where entrepreneurs can go for advice.

8.      Support for entrepreneurs to establish effective collaborative relationships, utilising open innovation /crowdsourcing, collaborative projects and (open) networks.

Action

NetworkedPharma is now establishing collaborative networks to address the above, and welcomes approaches from those interested in the possibility of working together for the good of the sector.  As a not-for-profit organisation we are also interested in discussions with potential patrons / sponsors / supporters.                       

Our next workshop on Open Innovation& Crowd Sourcing will be in April 2013.

BioSpring Ltd is a member of Networked Pharma Partnership, a not for profit organisation dedicated to assisting development of a new paradigm for drug discover & development

Networked Pharma Partnership; Building Innovative Networks in Drug Discovery & Development

A series of workshops are being run during 2012, leading to an international congress in mid 2013, which will bring together all stake-holders (Corporate Pharmas, SMEs, CROs, Universities, VCs, CVCs, Research Councils, Charities, Regulators & Government bodies etc.) to formulate the new business model(s) for the future success of the industry.

Follow us:

Twitter @NWkPharma,      #NWkRx