1. Successfully securing funding Drug discovery to University Spin-out Dr Kevin Adams Institute of Cancer Therapeutics and Incanthera Ltd

2. The valley of death Declan Butler (2008) Nature 453, 840-842

3. 3 hills and 2 valleys

4. 5 hills and 4 valleys Meslin et al (2013) Mapping the translational science policy ‘valley of death’ Clinical and Translational Medicine 2013, 2:14

5. The valley of death In vivo proof of conceptFirst in man clinical trial

8. …or is it? Bruce Booth, Forbes 22 May 2013

9. Biomedical catalyst Through targeted funding, the Biomedical Catalyst aims to bridge the so-called ‘valley of death' which can exist in getting ideas out of the lab and into the marketplace. The report shows that, in just over a year since it opened, the Biomedical Catalyst has: awarded over £120m in funding, over £80m of which is to support innovative, business-led research leveraged almost £70m of additional, project-specific private capital. Over 100 projects from all over the UK have been supported.

10. Big pharma are failing Not getting new drugs through trials Not getting new drugs to market Pipelines are poor for many

11. Consequences of failure Rethinking strategy Closing internal R&D sites Looking for late stage deals – short term Looking to pick up molecules from small biotechs and research institutes – longer term We need to see this as an opportunity

12. Big pharma as VCs Most of the big pharma companies have recently set up “investment companies” But everyone is trying to attract their interest. Supposedly looking at early stage investment But generally still want to see Phase 1 clinical data Need to have a good strategic fit.

13. Pharma influences VCs Size of failures has an impact on how VCs view risk. The more risky the less likely they are to put up money. Venture capitalists like to invest in things that they think big pharma will like. Need to consider this when constructing a pitch Sometimes investments aren’t always as rational as you might expect.

14. Trending in cancer. PhRMA (2012): Medicines in Development Cancer, 2012 Report This lists nearly 1000 anti-cancer drugs at preclinical and clinical development stage in the US alone http://www.phrma.org/sites/default/files/1000/phrmamedicinesindevelopmentcancer2 012.pdf

15. So what are pharma thinking? Analyses of these US cancer projects show that just eight drug targets account for around 40% of all projects in preclinical or clinical stages of development. Each of these eight targets was identified as having at least 24 individual clinical programmes Bruce Booth (2012): Cancer Drug Targets: The March of the Lemmings http://lifescivc.com/2012/06/cancer-drug-targets-the-march-of-the-lemmings/

16. Serine/threonine kinase Receptor tyrosine kinase Phosphatidylinositol 3' -kinase Receptor tyrosine kinase It might be unfair to lemmings but..

17. Start-up What do all these messages mean for a start-up gazing across the valley of death. Need to use this sort of information to develop your strategy. For me there are four things to focus on to give the best chance of success.

18. 4 vital ingredients

19. Product - ICT2588, a targeted cytotoxic Azademethylcolchicine Specific endo-peptidase cleavage by MT1-MMP Non-specific exopeptidase activity

20. Product Targeted Non-toxic Kills tumours

21. Protection Three patents First nearing end of national phase – recently granted in US Second in national phase Third recently filed – in conjunction with Stanford University

22. People Academic inventors still involved but in the background CEO Dr Simon Ward, serial entrepreneur with good VC connections Executive Director Dr Alan Warrander, former Director of Global Licensing at AZ Me as programme manager – background in industry Professor Chris Twelves – clinical oncology lead People are very important to VCs

23. Plan Know where you are and where you need to get to. Be honest and realistic about what you do/don’t know – find someone who does. Break it down into individual task with key value added milestones. Get some quotes for work to be done – realistic costs. Build in contingency and timeline flexibility. Understand the cash flow but more importantly the exit. Phase 1, Phase 2 or later?.

24. Some cancer deal examples OriginatorLicenseeTotal (M)Upfront (M)Stage At Signing S*BIOOnyx Pharma$550$25Phase I, TrubionFacet Biotech$206$20Phase I PDL BioPharmaBristol-Myers Squibb$710$30Phase I Merrimack PharmaceuticalsSanofi-Aventis$530$60Phase I Seattle GeneticsGenentech$860$60Phase II ArQuleKyowa Hakko Kogyo$123$30Phase I Kyowa Hakko KogyoAmgen$520$100Phase I ThromboGenics, BioInventRoche$775$50Phase I Lpath TherapeuticsMerck Serono$473$23Phase I Ardea BiosciencesBayer$407$35Phase I PharmacyclicsServier$39$11Phase I CelgeneAcceleron Pharma$1,878$45Phase I,

25. Plan Elevator pitch Executive summary Business pitch Business plan Practice and refine all the above but most importantly get out and deliver.

26. Plan Listen for feed back Learn from it Anticipate the negatives and turn to your advantage

27. Refining the Incanthera plan VC response in general was MMPs – failed as a target previously VDAs – failed in clinic Cytotoxics are old fashioned

28. From Overall and Kleifeld (2006), Nature Reviews:Cancer 6:227-239

29. MMP inhibitors fail Good news – MMPs are clearly a valid target More importantly, we aren’t trying to inhibit MMPs but are using their localised expression to target tumour vasculature

30. VDA failures Compounds include ASA404, ABT-751, Dolastatin-10, TZT-1027, ZD6126, CA1P and CA4P MPC-6827 MN-029. In all cases, cardiac toxicities are prevalent. Hollebecque et al (2012) Curr Opin Oncol. 24(3):305-315.

31. VDAs fail Good news – clearly pharma wants a good VDA targeting overcomes cardiotox issue ICT2588 even mentioned in Hollebecque et al (2012) as being a good way to overcome the problem.

32. Cytotoxics Yes they are old fashioned......but they work! Many of the most effective and widely used cancer drugs are still cytotoxics.

33. Incanthera success Took 2 years to get first funding of £350K – beware University legal teams – signed off in December 2011 A year later (end 2012) we were up to £1.2 million US based VC UK based Angel consortium This year we’ve had a letter from the Wellcome Trust offering investment of around £1.6 million in the form of a convertible loan (subject to contract).

34. Incanthera the future Enough funding to complete Phase 1 (subject to contract) Scale up chemistry and formulation development done. Toxicology studies currently being done Hope to start clinical trial by summer of 2014 A successful trial will probably result in a sale/licensing of the technology Aim to retain some of that funding for pipeline.