Table of Contents / Agenda

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1 Future Diagnostics What impact will Liquid Biopsy and other new cancer diagnostic techniques have on the sustainability of Living Benefit products? Lawrence Tsui, Global Products Actuary

2 Table of Contents / Agenda Why the focus on Cancer diagnosis? What is Liquid Biopsy? Other new Cancer diagnostic techniques Implications for insurers and reinsurers 2

3 Why the focus on Cancer diagnosis? 3

4 Before we start why the focus on Cancer diagnostic techniques? Our desire for longer healthier lives New discoveries from research Increasing technological advances Size of the prize Threats and opportunities for life and health 4

5 Progress is being made 5

6 Early detection of cancer has transformative power 6

7 But is earlier diagnosis sometimes too much of a good thing? Prognosis of Cancer Patients Life Expectancy Overdiagnosis? Diagnosed by Screening No Symptoms With Symptoms Life Extension with Treatment Diagnosed by Symptoms Theoretical Start of Cancer Current Diagnosis of Cancer Normal Life Expectancy 7

8 But is earlier diagnosis sometimes too much of a good thing? Prognosis of Cancer Patients 3. More over-diagnosis??? Life Expectancy Overdiagnosis? Diagnosed by Screening 2. Extension of Life Expectancy No Symptoms With Symptoms Life Extension with Treatment Diagnosed by Symptoms Theoretical Start of Cancer 1. Earlier Diagnosis of Cancer Normal Life Expectancy 8

9 What is Liquid Biopsy? 9

10 How is cancer diagnosed today? Routine exams Symptoms investigation Imaging determines location Biopsy confirms diagnosis Staging & grading CI event 10

11 What is liquid biopsy? 11

12 Why the attention given to liquid biopsy? Follow the money Top Players Funding to date Grail USD 1.6b to date Series B USD 300m May 2018 Guardant Health USD 550m to date Series E USD 360m May 2017 Data from PitchBook Data Inc cited in Wall Street Journal, 17 Nov 2017 Foundation Medicine 56.3% acquired by Roche for USD 1b+ investment in Jan 2015 Personal Genome Diagnostics USD 99.3m to date Series B USD 75m Jan 2018 Freenome USD 77.6m to date Series A USD 72m Mar-Aug 2017 Data from crunchbase.com and company websites 12

13 And the headlines Science, 19 Jan 2018 CancerSEEK is a liquid biopsy test for 8 cancer sites (based on ctdna from 16 genes, combined with 8 protein biomarkers), developed by a team led by scientists at Johns Hopkins. 1,005 people known to have cancer were tested with 70% detected (but only 46% in Stage 1). 812 healthy people with no cancer history were also tested with 7 (false) positives. Next step will be years of larger prospective clinical trials to demonstrate that the test improves overall cancer survival. 13

14 Is the Holy Grail just around the corner A study of 1,627 lives (878 with newly diagnosed cancer, 749 without) across 10 different types of cancer with accuracy of results ranging from 90% for Ovarian Cancer (10 cases) to 59% for Lung Cancer (73 cases) to < 10% for low-grade Prostate or Thyroid Cancers. and funded by GRAIL. 14

15 Other new Cancer diagnostic techniques 15

16 Not just liquid biopsy The Observer, 22 Apr 2018 A team of researchers at Dundee University have developed a new method offering much greater accuracy and reliability in the diagnosis of prostate cancer. The new ultrasound process called shear wave elastography (SWE) is not only more accurate, but is non-invasive and cheaper than existing methods. In testing, the new method was able to detect 89% of prostate cancers and could identify more aggressive cancers and those beginning to spread outside the prostate. 16

17 Not just liquid biopsy The Telegraph, 28 May 2016 Oncimmune were spun out from the University of Nottingham in 2002 to develop cancer diagnostic tests based on the body s natural antibody response to cancer cells. The company s EarlyCDT-Lung test has been extensively validated across peerreviewed journal articles with high levels of sensitivity and specificity. EarlyCDT- Lung has been commercially available for many years and can detect lung cancer up to 4 years before symptoms present. The company aims to develop similar tests for other cancer sites. 17

18 Cutting through the hype? Numerous biotech companies looking for additional funding or looking to show progress to investors issuing press releases to news organisations hungry for content What to look for: Publications in peer-reviewed scientific journals, with reproducibility of results Large-scale testing and clinical trials, including validation in healthy individuals Economically viable test costs in studies of benefit vs cost Applicability of test across a wide range of cancer types Interest from national health bodies Beware of biotech hype over substance! Wall Street Journal, 10 Apr

19 Reasons to be sceptical? Early pioneer of Liquid Biopsy with a particular focus on detection of actionable cancers (for which targeted therapy drug treatments are available) announced a suspension of its Liquid Biopsy product and research program. Identical samples sent for 2 different commercially available Liquid Biopsy tests (Guardant360 and FoundationOne) showed significant discordance in findings. Subsequent studies (JAMA Oncology Dec 2017) have shown similar discordance between different tests (Guardant360 and PlasmaSELECT). 19

20 Where are we today in the hype cycle? Things look promising for Relapse or recurrence High risk groups Guidance for treatment of histologically confirmed patients The jury is still out for General population screening of asymptomatic individuals Heitzer, Perakis, Geigl, Speicher, Precision Oncology Potential of liquid biopsies for the early detection of cancer, Nature Partner Journals Bettegowda, et al, "Detection of circulating tumor DNA in early- and late-stage human malignancies", Science Translational Medicine, Feb

21 Implications for insurers and reinsurers 21

22 What should we make of this? 22

23 What does this mean for the insurance industry? Cancer is the leading cause of CI claims Liquid biopsy impacts.. 1. the number and timing of claims 2. cancer definitions, product design 3. pricing and long term guarantees 4. anti-selection risk, how we underwrite i.e. pretty much everything Mortality improvements may also be observed in the future 23

24 How can the insurance industry respond? Know your exposure Strong defence Active engagement Early warning systems Above all maintain discipline, keep stakeholders informed 24

25 With careful proactive management, we can maintain the important role of critical illness products in meeting real needs and helping society respond to adversity 25

26 Summary Source: Press release 1 March 2018 on joint paper from ASCO (American Society of Clinical Oncology) and CAP (College of American Pathologists) - Circulating Tumor DNA Analysis in Patients With Cancer. For the foreseeable future, histopathology will remain the standard for cancer diagnosis and staging All life and health insurance companies should be actively monitoring this space for developments 26

27 Ongoing activity Swiss Re activity 27

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29 Legal notice 2018 Swiss Re. All rights reserved. You are not permitted to create any modifications or derivative works of this presentation or to use it for commercial or other public purposes without the prior written permission of Swiss Re. The information and opinions contained in the presentation are provided as at the date of the presentation and are subject to change without notice. Although the information used was taken from reliable sources, Swiss Re does not accept any responsibility for the accuracy or comprehensiveness of the details given. All liability for the accuracy and completeness thereof or for any damage or loss resulting from the use of the information contained in this presentation is expressly excluded. Under no circumstances shall Swiss Re or its Group companies be liable for any financial or consequential loss relating to this presentation. 29