Commercializing Aging Research Series

Industry Overview

BIG DATA IN AGING AND AGE - RELATED DISEASES

Analysis of the Anti-Aging Market 1 aginganalytics.com bg-rf.org.uk biotech.ai BIG DATA IN AGING TABLE OF CONTENTS AND AGE - RELATED DISEASES

TABLE OF CONTENTS...... 3 INTRODUCTION...... 4 INDUSTRY OVERVIEW...... 7 INDUSTRY TRENDS...... 10 CHALLENGES IN COMMERCIALIZING LONGEVITY RESEARCH...... 12 EARLY TRIALS AND FAILURES...... 14 Telomerase - Geron...... 14 Resveratrol - Elixir & Sirtris Pharmaceuticals...... 14 Contributing Parties: TRENDS IN BIG PHARMA...... 15 OPPORTUNITY AND MARKET SIZE...... 16 COMPANY PROFILES...... 18 Biogerontology Research Foundation (BGRF) Calico Life Sciences, LLC ...... 19 Key Personnel...... 19 Aging Analytics Agency Background...... 19 Strategy...... 20 Analysis...... 20 Human Longevity, Inc. (HLI)...... 22 Key Personnel...... 22 Assisted by Background...... 22 Strategy...... 22 VITAL analytical tool Analysis...... 24 Insilico Medicine (ISM)...... 26 Key Personnel...... 26 Background...... 26 Strategy...... 27 Analysis...... 27 Canada Cancer and Aging Research Laboratories, Inc (CCARL)...... 30 Key Personnel...... 30 Background...... 30 Strategy...... 30 Analysis...... 31 Vision Genomics, LLC (VG)...... 32 Key Personnel...... 32 Background...... 32 Strategy...... 32 Analysis...... 33 Atlas Regeneration, Inc...... 34 Key Personnel...... 34 Background...... 34 Strategy...... 35 Analysis...... 35 CONCLUSION...... 38 REFERENCES...... 42 Designed by Future Technologies Media Group

2 Executive Summary Analysis of the Anti-Aging Market 3 COMMERCIALIZING AGING RESEARCH SERIES

COMMERCIALIZING AGING RESEARCH SERIES INTRODUCTIONINTRODUCTION

As both the proportion of older people and the length in 2003 it was announced that the human genome As both the proportion of older people betes Federation (IDF) study estimated of life increase throughout andthe the world, length ofhow life increasewill aging throughout that had387 million been people sequenced, have diabetes there in was much optimism that the world, how will aging affect health 2014 and this disease caused at least affect health care and economiccare and costs? economic Age-related costs? Age-related USDwe 612 hadbillion entered dollars in healtha new expendi age -of human health where diseases such as cancer, heart disease, ture in 2014 – 11% of total spending on diseases such as cancer, heartstroke anddisease, diabetes stroke already and comprise a adults.conditions The IDF estimates like cancer that the and num -aging would be easily substantial economic and public health ber of people with diabetes will rise to diabetes already compriseburden. a substantial In 2012 World economic Health Organiza - 592 cured.million. The presumption was that it would be a simple tion reported 14.1 mln of new cases. The and public health burden. Agrowth recent rate analysis for cancer of cases global per year Whilematter some progress of decoding has been the made genes in in the genome sequence FIGURE 1: Relative life extension potential of biomedical interventions has decreased due to enhancements combating age-related illnesses, much cancer trends by the Economistin the technologies, Intelligence treatment Unit (EIU) became moreto needs determine to be done. the When causative in 2003 it genes or mutations that cheaper. Thus, the cost of full cancer was announced that the human genome estimated that the cost of thetreatment 13 million including new therapies cancer totaled had underlie been sequenced, specific there pathological was much phenotypes suchas canceras or aging. With the causative function. Another speculative area is replacement and regeneration pharmacology hold sequencing individual human genomes along with $100 bln. in 2014. In fact, the EIU esti- optimism that we had entered a new age gene identifed we could then design or longevity gene therapy designed to cases in 2009 totals at leastmates US$286 that the billion number [1]. of In new fact, cancer of humancancer health or aging. where conditions With the like causative geneenormous identifieddiscover potential wetherapies for restoring to target lost function. the identifed Another improvethe ability stress to probe resistance, gene and protein damage expression, cases will rise to 17 million by 2020 and cancer and aging would be easily cured. genomic region thus curing the disease. repair, recycling, endogenous speculative area is longevity gene therapy designed to methylation and microbiome data allows us to collect the EIU estimates that reach 27 million by 2030. These costs The presumption was that it would be a could then designAs the knowledge or base aging processes regenerative abilities and many other are likely to dramatically escalate as the simple matter of decoding the genes in improve continuesstress resistance, to grow damage and many repair, biomedical recycling, mechanismsan unprecedented providing amount of maximum data that only a few years developing world begins to live longer the genome sequence to determine the the number of new discoverendogenous therapiestechnologies regenerative to continue abilities and to advance many other and longevityago was beneft. impossible. In Coupled 2012 CRISPR/ with the advent of new and adopt Western diets and lifestyles. causative genes or mutations that underlie converge with information technology, Cas9 genome engineering/editing cancer cases will rise Additionally, a recent International Dia- specifc pathological phenotypes such target mechanismsthe identifiedmany providing scientists maximum are hypothesizing longevity benefit. about tool wasdata-mining, frst shown machine-learning, to work in human and bioinformatics The S-curvesthe various for relative interventions mass adoption that and may longevity have cell culture.algorithms, It allowswe are now scientists able to todissect edit and probe the the potential to augment human longevity genomes with good effciency, fexibility to 17 million by 2020 genomicbenefits region of these thus approaches are illustrated in Figure 1. workings of the human body in an unprecedented and prevent or postpone various age- and huge precision. In past years there and reach 27 million curing the disease.related diseases. And while there is no were way many to understand researches the conducted, molecular mechanisms e.g. behind consensus in the academic community, frst monkeys with targeted mutations That promise has largely been unfulfilled, as the disease and aging. With these new capabilities in mind, by 2030. These most scientists tend to agree that the frst was born, and even preventing HIV-1 process frontierof untangling is developingthe complexity pharmaceutical of biology infectionmany preventionindustry players in both humans. in the pharmaceutical The and As thehas knowledge proveninterventions to be far more (geroprotectors) difficult than anticipated. that can S-curvesdata-analysis for relative industries mass adoptionfeel that we and now have the costs are likely to be brought to market by pharmaceutical longevity benefts of these approaches Realizingcompanies that many diseases directly, such through as cancer off are label are illustratedability to tackle in Figure difficult 1. problems such as aging that dramatically escalate base aging processes complexuse biological or even phenomena over the where counter. many Another genes or have so far been recalcitrant to study. With the recent frontier is regenerative medicine. Stem That promise has largely been unful- as the developing continuesgenomic tocell regionsgrow treatments, act in concert organ to create replacement pathological filled,headline as the grabbingprocess entrancesof untangling of new the players such as phenotypes,and new regeneration approaches pharmacologyhave been necessary. hold complexityCalico andof biology Human Longevityhas proven Inc. to and be the impressive world begins to live and many biomedicalenormous potential for restoring lost far more difficult than anticipated. Real- Recently, the continuing decrease in costs of quality and pedigree of the principals involved, the longer and adopt technologies continue Western diets and 4 Executive Summary to advance and Industry OverviewAnalysis of the Anti-Aging Market 5 | 5 lifestyles. Additionally, a recent WHO study estimated converge with information technology, many scientists that the loss in economic output from heart disease, are hypothesizing about the various interventions that stroke and diabetes in 23 low and middle-income may have the potential to augment human longevity nations (comprising ~80% of the total chronic disease and prevent or postpone various age-related diseases. mortality in the developing world) totaled US$84 billion And while there is no consensus in the academic between 2006 and 2015 and is expected to double in community, most scientists tend to agree that the first the short-term [1]. frontier is developing pharmaceutical interventions (geroprotectors) that can be brought to market by

While some progress has been made in combating age- pharmaceutical companies directly, through off label related illnesses, much more needs to be done. When use or even over the counter. Another frontier is regenerative medicine. Stem cell treatments, organ

4 | Big Data in Aging and Age-related Diseases izing that many diseases such as can- ready have compounds or treatments in cer are complex biological phenomena various stages of development and test- where many genes or genomic regions ing. Most famous compound is Rapa- INDUSTRY act in concert to create pathological mycin, FDA-approved drug, which has phenotypes, new approaches have been been developed by Novartis and is cur- necessary. Recently, the continuing de- rently used to prevent organ rejection. crease in costs of sequencing individual Research suggests that Rapamycin OVERVIEW human genomes along with the ability slows both normal aging processes and to probe gene and protein expression, the progression of age-related maladies methylation and microbiome data allows such as Alzheimer’s disease, cancer, The anti-aging therapeutics industry is wit- tive products in the technology sector and us to collect an unprecedented amount and cardiovascular disease. Scientists nessing the dawn of a new era with the has been repeatedly eying opportunities in of data that only a few years ago was at the University of Wisconsin-Madison emergence of Calico, Human Longevity Inc. the biotechnology and biomedicine areas. impossible. Coupled with the advent of working on strategy for reducing unde- (HLI) Insilico Medicine, Atlas Regeneration Additionally, Calico has been able to recruit new data-mining, machine-learning, and sirable side effects that can allow sci- Vision Genomics, Canada Cancer and Ag- heavyweights in the research and biotech- bioinformatics algorithms, we are now entists to start remove human trials on ing Research Laboratories and many other nology felds to join this effort. Chief among able to dissect and probe the workings aging or age-related diseases. companies into the marketplace with a vari- these hires are CEO Arthur Levinson who of the human body in an unprecedented ety of business models (Figure Additionally, served as CEO of Genentech, and is chair- way to understand the molecular mech- Despite this growing interest and activ- these companies are supported by credible man of the board of Apple, and previously anisms behind disease and aging. With ity, we are currently still in the relative new players in the feld; Google in the case served as a director of Google and Roche, these new capabilities in mind, many in- infancy of the anti-aging therapeutics in- of Calico, and Craig Venter and Robert Hariri CSO David Botstein, a prominent geneticist, dustry players both in the pharmaceuti- dustry. As such, there will likely be many in the case of HLI. Google brings expertise in former director of the Lewis-Sigler Institute cal and data-analysis industries feel that successes and failures in the coming managing, manipulating and leveraging Big for Integrative Genomics at Princeton Uni- we now have the ability to tackle diffi- years. This report provides an analysis Data towards highly innovative and disrup- versity, and former VP of Science at Genen- cult problems such as aging that have of the current state of the industry, the so far been recalcitrant to study. With challenges facing both the research and the recent headline grabbing entrances development of longevity therapeutics, of new players such as Calico and Hu- relevant trends in the longevity and big man Longevity Inc. and the impressive pharma industries, an analysis of the quality and pedigree of the principals in- opportunity and market size for longev- volved, the anti-aging industry is poised ity therapies, a history of previous ear- to explode. Among Big Pharma and the ly trials and failures and profiles of the biotechnology industry, this renewed important companies and players in the interest is evidenced by investments industry. by newer entrants such as AbbVie and Celgene, along with companies such as GlaxoSmithKline and Novartis that al- Atlas Regeneration, - Personalized regenerative medicine Inc R&D-stage - Drug discovery and repurposing for age-related diseases - Safety standards in the feld iPSC cells WE ARE NOW ABLE TO DISSECT AND PROBE THE WORKINGS OF THE HUMAN BODY IN AN UNPRECEDENTED WAY TO UNDERSTAND THE MECHANISMS BEHIND DISEASE AND AGING FIGURE 2 : Business models of recent startups commercializing aging and longevity research

6 Executive Summary Analysis of the Anti-Aging Market 7 Industry Overview | 7 COMMERCIALIZING AGING RESEARCH SERIES

biotech, Navitor Pharmaceuticals, Pro- lated diseases. IBM and the First Oncology teostasis Therapeautics, Elysium Health, Research and Advisory Center will provide CohBar, and Alkahest, see [4]), the most the know-how and methods for assisting recent entries to the industry focus much clinicians in making treatment decisions more heavily on bioinformatics and data with support from IBM Watson Health, de- analysis. As such, in addition to the entry of veloped by IBM and OncoFinder system de- Calico and HLI in the industry, several small- veloped by FORAC. er bioinformatics / big data analysis compa- nies have also entered the market. These in- Additionally, a large number of research clude Insilico Medicine, Atlas Regeneration institutions and funding agencies now ex- Vision Genomics and the Canadian Cancer ist that focus on aging research. Some of and Aging Research Laboratories. Insilico the more prominent institutions include Medicine, located at the Johns Hopkins Uni- the National Institute on Aging, the Buck versity Emerging Technology Centers with Institute for Research on Aging, the Salk large R&D and clinical operations in Eastern Glen Center for Aging Research, the Albert Europe, has developed a sustainable busi- Einstein College of Medicine Institute for ness model, which involves partnering with Aging Research, Wake Forest Institute for Big Pharma, academic and clinical institu- Regenerative Medicine and the UC San Di- tech, and VP Aging Research Cynthia Ken- and its commercial expertise to bring new tions on drug repurposing and personalized ego Stein Institute for Research on Aging. yon, a pioneer in the feld of aging research, discoveries to market. In the case of HLI, medicine as well as licensing its fagship In 2013 the Buck Institute reported the for- founder of Elixir Pharmaceuticals and a Celgene, a manufacturer of drug therapies OncoFinder and GeroScope drug platforms mation of its frst spin off, Delos, a Dela- UCSF Distinguished Professor of Bichem- for cancer and infammatory disorders has to other startup companies. The company ware corporation, then a wholly owned sub- istry and Biophysics. In the case of HLI, made an undisclosed equity investment in is collecting massive statistical databas- sidiary. The company was founded on the CEO Craig Venter has been one of the most HLI [3]. Additionally, Celgene has reached In the case of HLI, CEO Craig Venter has been one world’s best selling drugs Humira, has agreed to invest es of aging-specifc pathologic changes, basis of discoveries at Buck and a unique successful and infuential fgures in the bio- an agreement with HLI to license, develop, tissue-specifc and age-specifc drug ef- chemistry technology acquired from Biot- technology world, being one of the frst to and co-promote Celgene’s proprietary pla- of the most successful and influential figures in the $250 million in collaboration with Calico and up to an fects, while focusing on signalome-level ica Technologies, which allows synthesis sequence the human genome genome. He cental stem-cell population, PSC-100 [3]. It tissuespecifc changes and screening for of unique rapamycin analogs (rapalogs). biotechnology world beingalso one foundedof the first the to successful sequence companies additionalis thought $500 that HLI million, will sequence both of and which char- will be matched drugs and drug combinations that suppress Another startup company co-founded by Celera Genomics and Synthetic Genom- acterize PSC-100 at the molecular level to these age-related changes or mimic youth- Nir Barzilai of Albert Einstein College of the human genome and havingics as founded well as research successful institutes such as bycomplement Google [2]. the AbbVie data Celgene will provide has generat scientific- and clinical ful states in aged tissues. Since many of the Medicine and Pinchas Cohen of University The Institute for Genomic Research (TIGR) ed from Phase I studies of this cell popula- drugs were tested in human patients and of Southern California, CohBar, Inc focus- companies Celera Genomics,and theand J. SyntheticCraig Venter Genomics Institute (JCVI). His developmenttion. This data support will likely andbe used its tocommercial explore expertise to have vast clinical data, the company aims ing on mitochondrially-derived peptides co-founder, Robert Hariri, is a pioneer in stem different applications for PSC-100, including as well as research institutes such as The Institute bring new discoveries to market. to publish the frst list of geroprotective reg- (MDPs),went public on January 7th, 2015 cell research and is the former CEO, CSO, testing against sarcopenia, or age-related imens in the near future. Insilico’s research on the TSX Venture Exchange in Canada, chairman and founder of Celgene. For both muscle loss. HLI also announced a multi- for Genomic Research (TIGR) and the J. Craig Venter in aging and age-related diseases resulted e raising US $11.25 million in capital with a Calico and HLI not only are the quality and year agreement with Genentech, a member in 17 peer-reviewed research publications market capitalization of approximately $50 Institute (JCVI). His co-founder,credibility Robert of the Hariri, principals is a stellar, but also In ofthe the case Roche of Group,HLI, Celgene, to conduct a whole manufacturer ge- of drug and numerous presentations at academic million. John Amatruda and David Sinclair established pharmaceutical companies nome sequencing of tens of thousands of conferences in 2014 alone. In June 2015, (ex-Sirtris) are listed as founders and ad- pioneer in stem cell researchhave and backed is the both former of these CEO, new ventures therapiesde-identifed for samplescancer fromand Genentech.inflammatory HLI, disorders has IBM signed a collaboration agreement with visors. Research from top-tier institutions lending further legitimacy to the industry. using proprietary tools and unique exper- the First Oncology Research and Advisory like Albert Einstein and Buck will likely pro- CSO, chairman and founderWith of respectCelgene. to Calico, AbbVie, the mak- madetise, willan undisclosedsequence genomes equity to 30xinvestment cover- in HLI [3]. Center (FORAC)- Eastern European R&D vide the industry with future commercial- er of one of the world’s best selling drugs age and analyze the data. Financial details Additionally, Celgene has reached an agreement with Center of Insilico Medicine for the develop- ization opportunities, and there are a myr- Humira, has agreed to invest $250 million of the agreement were not disclosed. ment of a medicine platform.The platform iad of startups emerging in Europe, China, in collaboration with Calico and up to an ad- For both Calico and HLI not only are the quality and HLI to license, develop, and co-promote Celgene’s will utilize novel clinical decision support Japan and India that will receive coverage ditional $500 million, both of which will be While previous efforts at longevity thera- solutions to extend healthy productive lives in the follow up versions of this report. credibility of the principals matchedstellar, butby Google also established[2]. AbbVie will provide proprietarypeutics have placental largely focused stem-cell on a specifcpopulation, PSC-100 of patients with cancer and other age-re- scientifc and clinical development support molecule or pathway (e.g. L-Nutra, Metro- pharmaceutical companies have backed both of these [3]. It is thought that HLI will sequence and characterize 8 Executive Summary Analysis of the Anti-Aging Market 9 new ventures lending further legitimacy to the industry. PSC-100 at the molecular level to complement the data With respect to Calico, AbbVie, the maker of one of the Celgene has generated from Phase I studies of this

8 | Big Data in Aging and Age-related Diseases aging and age-related diseases,COMMER buildingCIALIZING AGING Additionally,RESEARCH SERIES in contrast to earlier efforts statistical databases, building models of in the antiaging industry, these new ef- INDUSTRY TRENDS aging, and in silicoI Nscreening D U of thousands ST RY forts T are R being E N supported D S by established of drugs and drug combinations to address pharmaceuticals virtually from the out- Whereasage-related previous diseases. efforts at drug Insilico discovery Medicine is set.data AbbVieis now possible. and Google However, have the main pledged challenges to andalso treatment partnering have largely with beenother driven companies by the such fundnow relate Calico to developing with up new to computational $1.5 billion methods dol-

pharmaceuticalas Vision Genomics, industries focus Canadian on specific Cancer targets and larsto translate while wholeCelgene human has genome, obtained microbiome, an equi and- Whereas previous efforts at drug discov- nomics spaces. Such initiatives include Aging Research Laboratories, Atlas Regen- ty investment and licensing agreement and molecules, this new era appears driven more protein sequencing data into the language of human ery and treatment have largely been driven Google Genomics and Google Health eration and IBM to further develop and pro- with HLI. by the pharmaceutical industry’s focus on and investments in companies such as by moteBig Data its analysis. algorithms With thefor cost other of performingdiseases and health and disease using human phenotype data. This specifc targets and molecules, this new Pathway Genomics and 23andMe. It is genomemarkets. sequencing continually decreasing, the is exemplified by three of the more notable entrants era appears driven more by Big Data anal- thus highly likely that Google’s expertise ability to generate large sets of relevant sequencing in this field, Calico, Human Longevity Inc. and Insilico ysis. With the cost of performing genome in Big Data approaches will be harnessed sequencing continually decreasing, the towards Calico’s goals. ability to generate large sets of relevant se- quencing data is now possible. However, HLI, founded by human genome sequenc- the main challenges now relate to develop- ing pioneer Craig Venter, is building the ing new computational methods to trans- world’s most comprehensive human gen- late whole human genome, microbiome, otype and phenotype database to tackle and protein sequencing data into the lan- the diseases associated with aging-related guage of human health and disease using human biological decline. This requires se- human phenotype data. This is exempli- quencing hundreds of thousands or even fed by three of the more notable entrants millions of genomes in an effort to compu- in this feld, Calico, Human Longevity Inc. tationally identify traits linked to longevity. and Insilico Medicine, that all to differing With the immense bioinformatics chal- degrees have a focus on using compu- lenges inherent in analyzing and interpret- tational and bioinformatics approaches. ing such large amounts of data, HLI has In fact, one of the biggest challenges for hired Franz Och the head of Google Trans- these companies will be how to interpret late to be its new Chief Data Scientist. Ad- the vast amount of biological data avail- ditionally, HLI has partnered with Personal able. New computational tools and tech- Genome Diagnostics, Inc., a cancer ge- niques will need to be developed in order nome analyses solution provider, to use its to make these data interpretable and clini- analysis tools on HLI data. cally actionable. Similarly, Insilico Medicine is using an al- Calico is funded by the Internet search gorithmic approach to analyze human giant Google. Which has made several tissue-specifc transcriptome, microRNA, moves to apply its expertise in search, methylome, proteome and genomic profles algorithms and data management in the to identify pathways related to aging. This pharmaceuticals / diagnostics / ge- includes searching for relevant patterns in

ABBVIE & GOOGLE HAVE PLEDGED TO FUND CALICO WITH UP TO $1.5 B ILLION DOLL ARS 10 | Big Data in Aging and Age-related Diseases

10 Executive Summary Analysis of the Anti-Aging Market 11 ing has largely been studied using model in assessing the biology of aging, such organisms such as C. elegans and S. cer- as altered signaling pathways or expres- CHALLENGES IN evisiae, there are dangers that therapies sion of particular molecules that serve based on such research will not have as potential readouts of the aging pro- the same effects in humans. These con- cess. Therefore, the most common way COMMERCIALIZING cerns apply equally to therapies shown to perform such studies is to follow ani- to function in animal models such as mals until they die in order to record their mice, rats or primates. Examples of such lifespan. Such an approach is impracti- LONGE VI T Y RESEARCH failures include work on commercializ- cal for humans. ing research involving telomerases, res- veratrol and the sirtuin pathways. But, Lastly, while there may be current drugs there are new innovative approaches for that have antiaging properties (rapamy- a drug testing process, e.g. tissues cre- cin, aspirin, ibuprofen, statins, beta block- Since the anti-aging therapeutics mar- any drug in clinical trials. Thus, such tri- ated with a 3D bioprinter can be used in ers, etc…), these are weakly prescribed, as ket is still in its infancy, there are sever- als measuring life-expectancy gains in clinical trials of drugs, thereby replacing many of them are generic drugs. Bringing al challenges to the commercialization humans over entire lifespans would be human participants and reducing costs therapies based on these drugs to mar- of longevity research. As such, there very diffcult and expensive to conduct for pharmaceutical companies. An add- ket would likely be prohibitively expensive are no clear business models, no indus- and would likely be subject to a diffcult ed diffculty even when studying model since any company attempting to do so COMMERCIALIZING AGING RESEARCH SERIES try lobby, and an uncertain regulatory regulatory environment. organisms is that there is no real agree- would be unlikely to recoup the regulato- framework. In fact, as the FDA does not ment in the feld on what criteria to use ry and development costs. consider “aging” a medical condition, no Such diffculties make venture capital in- treatments that specifcally target aging vestment in the anti-aging therapeutic in- can be offered on the market. Thus, the dustry quite challenging. Similarly to bio- only way to bring treatments to market is medical technologies with much longer to target specifc age-related conditions gestation cycles than other industries, the such as cancer, heart disease, diabetes road to commercializing anti-aging ther- and various neuromuscular disorders. In apeutics is likely to be as long or longer the future, with a large enough industry than those typical in the pharmaceutical lobby, it may be possible to reverse the industry. Due to the regulatory approvals FDA’s position on aging. required for such treatments, increased development costs and lengthening of the Notwithstanding these challenges, there investment cycle is to be expected. are additional inherent diffculties and complexities to bringing treatments that Beyond the fnancial and regulatory is- target aging to the marketplace. Be- sues surrounding this industry, there are cause human lifespans are much longer likely to be many failures ahead for com- than that of model organisms, it could panies looking to commercialize such re- take decades to evaluate the effects of search. Since to date, the biology of ag-

THE ROAD TO COMMERC IALIZING ANTI- AGING THERAPEUTICS IS LIKELY TO BE AS LONG OR LONGER THAN THOSE TYPICAL IN THE PHARMACEUTICAL INDUSTRY

12 Executive Summary Analysis of the Anti-Aging Market 13

or primates. Examples of such failures include work Lastly, while there may be current drugs that have anti- on commercializing research involving telomerases, aging properties (rapamycin, aspirin, ibuprofen, statins, resveratrol and the sirtuin pathways. beta blockers, etc…), these are weakly prescribed, as many of them are generic drugs. Bringing therapies

An added difficulty even when studying model based on these drugs to market would likely be

organisms is that there is no real agreement in the prohibitively expensive since any company attempting field on what criteria to use in assessing the biology of to do so would be unlikely to recoup the regulatory and

aging, such as altered signaling pathways or expression development costs.

of particular molecules that serve as potential readouts of the aging process. Therefore, the most common way

to perform such studies is to follow animals until they die in order to record their lifespan. Such an approach

is impractical for humans.

Industry Overview | 13 COMMERCIALIZING AGING RESEARCH SERIES

TRENDS IN BIG PHARMA EARLY TRIALS AND FAILURES this outsourcing of initial development and early Global M &In A Q3 deals 2015 in deal the volumehealthcare increased / life sciences by 59% III levels. Thus, this outsourcing of initial sector wereto an $67.6 unprecedented billion compared $317.4 to billion 46 transac in the - developmentdiscovery and early activities discovery can activitiesdramatically mitigate risk. tions in Q2 2015 resulting total closed deal can dramatically mitigate risk. TELOMERASE - GERON have been found to dramatically increase first half of 2014value [9]. of $72.2Some billion. of the Some more of notable the notable deals lifespan in diverse organisms such as ro- deals were between Celgene and Recep- It is within this landscape that the creation of were between Novartis and GlaxoSmithKline, Bayer It is within this landscape that the creation of One of the frst companies to tout an ati-ag- dents, primates, roundworms and yeasts. tos, Pfzer and Hospira, Merck KGaA and companies such as Calico and HLI should be ing cure was Geron, established in 1992 by The strategy of both companies relied on and Merck, SigmaAldrichRoche’s acquisition Corp. Inof InterMune, November Pfizer’s 2015 viewed. Thesecompanies companies such believeas Calico that and they HLI should be Michael West. Geron was based on work fnding compounds similar to resveratrol Pfzer and Allergan announced the “take have the knowledge and ability to dramati- viewed. These companies believe that they have the that found that the enzyme telomerase, (a polyphenol present in red wines and red failed takeoverover bid of of the AstraZeneca year in health for care$118 industry” billion and cally shorten the long development cycle of which extends the ends of chromosomes grapes) that can upregulate the expres- AbbVie’s cancelledwith total $55 value billion of $150 acquisition billion. Closed of Shire. vol - bringing knowledgetherapeutics and to market. ability Additionalto dramatically- shorten the (called telomeres), could reverse the short- sion of the mammalian sirtuin gene SIRT1 ume deals in biotech increased by 6x YoY ly, they believe their approaches can also in- ening of telomeres that occurs with aging. that is thought to mimic the effects of CR. basis in Q2 2015 from $1,8bln in 2Q2014 crease thelong success development of therapeutics cycle ofby bringingmov- therapeutics to Therefore, it was believed that increasing to $10,8bln in 2Q2015 (PwC,2015). ing towards higher levels of personalization While one of the drivers for such deals has been tax market. Additionally, they believe their approaches can the expression of telomerase might prevent However, there has been some contro- in therapies or combinations of therapies for telomere shortening, thus delaying the ag- versy as to whether resveratrol is acting inversion, wherebyWhile one companies of the drivers usually for such domiciled deals hasin specifc conditionsalso increase and diseases.the success While of pre therapeutics- by moving ing process. However, later work found that through the sirtuin genes as several stud- been tax inversion, whereby companies vious “Big Data” style efforts such as those towards higher levels of personalization in therapies or overactive telomerase was often a hallmark ies have been published that both support Ireland or theusually UK are domiciled acquired in by Ireland companies or the (previously)UK are by Rosetta Inpharmatics (acquired by Mer- of cancerous cells. This presents a safety and contradict these fndings [5]. The ac- domiciled inacquired other jurisdictions by companies to take (previously) advantage domi - ck) maycombinations not have been of successful, therapies for these specific conditions and concern as any telomerasebased therapy quisition of Sirtris in 2008 for $720 million ciled in other jurisdictions to take advan- new companies believe that with newer might induce cancer. As such, Geron has by GlaxoSmithKline and Elixir’s $500 mil- of lower corporatetage of taxlower rates, corporate taxes taxare rates, not the taxes only are and cheaperdiseases. sequencing While and previous high-through “Big Data”- style efforts such shifted its research focus away from lon- lion option deal in 2009 with Novartis was not the only motivating factor. With shrink- put phenotyping technologies that such motivating factor. With shrinking product pipelines as those by Rosetta Inpharmatics (acquired by Merck) gevity research to cancer by searching for viewed at the time as a vindication of ap- ing product pipelines and patent cliffs ap- approaches are likely to bring signifcant compounds that reduce telomerase activity proaches that mimic CR. However, stud- and patent cliffsproaching, approaching, many companies many companies are choosing are returns. Whilemay not virtually have all been Big Pharmasuccessful, com -these new companies rather than enhance it. ies from Amgen and Pfzer in 2010 found to exploit M & As to both diversify their panies utilize some form of bioinformatics believe that with newer and cheaper sequencing and that resveratrol did not activate SIRT1 choosing to productexploit Mportfolios & As to andboth also diversify to conversely their analysis, only GlaxoSmithKline, Novartis, RESVERATROL - ELIXIR & [6,7]. Additionally, Elixir was shut down product portfoliosbecome and more also specialized to conversely in areas become such as more Celgene high-throughput(through HLI) and phenotypingAbbVie (through technologies that such SIRTRIS PHARMACEUTICALS in 2010 after having burned through $82 personalized medicine. Calico) and Daiichi Sankyo are known to million in venture capital funding while specialized inAdditionally, areas such due as topersonalized the high risks medicine. inherent be pursuingapproaches age-related are studies. likely toThis bring is ex significant- returns. Two of the earliest companies in the frst the Sirtris facility of GlaxoSmithKline was in developing therapeutics, many compa- pected to change with the entry of HLI and wave of antiaging pharmaceuticals were shuttered in 2013, with many of its em- nies have been making smaller internal Calico into the marketplace bringing much ployees laid off. While development of the Elixir Pharmaceuticals, cofounded in 1999 Additionally,investments due to the highin R &risks D activities inherent by in eschew - needed credibilityWhile virtually and media all Big attention Pharma to the companies utilize some by Leonard Guarente and Cynthia Kenyon Sirtris resveratrollike compound SIRT501 ing investment in early discovery or phase anti-aging therapeutics market. form of bioinformatics analysis, only GlaxoSmithKline, (now with Calico) and Sirtris Pharmaceu- has been terminated, an alternative lead developing therapeutics,I studies. Instead, many such companies companies have have ticals founded in 2004 by David Sinclair. compound, SRT2104, which is dissim- pursued the strategy of acquiring smaller been making smaller internal investments in R & D Novartis, Celgene (through HLI) and AbbVie (through Both companies attempted to mimic ilar to resveratrol, is still in development companies or startups with potential prod- the effects of caloric restriction (CR) that to treat ulcerative colitis, diabetes and a activities byucts eschewing closer to investment the validation in early or phase discovery II or Calico) and Daiichi Sankyo are known to be pursuing host of infammatory diseases [8]. or phase I studies. Instead, such companies age-related studies. This is expected to change with have pursued the strategy of acquiring smaller the entry of HLI and Calico into the marketplace companies or startups with potential products bringing much needed credibility and media 14 Executive Summary closer to the validation or phase II or III levels. Thus, attentionAnalysis of tothe the Anti-Aging anti-aging Market therapeutics15 market.

Industry Overview | 15 COMMERCIALIZING AGING RESEARCH SERIES O PP O R T U N I T Y A N D M A R K E T S I Z E

OPPORTUNITY AND MARKET SIZE

Over the last decade, studies in anti-aging ulation). In Western Europe and Japan the have had a signifcant breakthrough allow- percentage of this age group is expected to ing cell therapy and genome editing sectors be even higher, accounting for about 20% to grow into a global industry that continues and 28% respectively. Baby boomers are to appeal more and more investors. In 2014, expected to be the major factor stimulating regenerative medicine companies raised demand for anti-aging products. Another ty is enormous. For forecasting purposes, Additionally, as attested by the entry of $6.3 billion including $3 billion raised by aspect to be considered is the growth of In 2013, Allied Market Research estimated that the be compared to treatments for chronic disease. gene and gene-modifed cell therapy com- wealthy individuals in developing countries. potential treatments for the prevention of Google, there is large potential for compu- panies, while the initial public offering (IPO) By 2018 the number of high-income house- regenerativeage-related medicine diseases industry, can of likelywhich be anti-aging com- tational approachesAs an inexample, developing treatment thera- of depression, diabetes, market for biotech companies was worth holds (over $25,000 a year) is projected to pared to treatments for chronic disease. peutics in the anti-aging and pharmaceu- Parkinson’s disease and multiple sclerosis which are about $1.37 billion. In accordance with Al- increase to 30 percent where major growth is currentlyAs a smallan example, part, wastreatment worth of $16.4 depression, billion withtical industries. In fact, it is likely that Big liance for Regenerative Medicine (ARM) is driven by Asia Pacifc region. Based on diabetes, Parkinson’s disease and mul- Data approaches in aging research may a compound annual growth rate of 23.2% [10]. It is relatively rare in the population can generate significant report (2014) investment infow from dif- Transparency Market Research, global an- tiple sclerosis, which are relatively rare result in improving R&D productivity in Big in the population, can generate signif- Pharma by providing for early project ter- ferent types of fnancings in 2014 has in- ti-aging market value will rise to US$191.7 estimated that by 2020, this market will be worth $67.6 revenues over time due to the long lifespans of creased considerably relative to 2013 in all billion by the end of 2019. Key players in the cant revenues over time due to the long mination, drug repositioning, better clinical the segments. The growth in the anti-aging pharma market defnitely feel the overall billion dollars.lifespans Such ofnumbers patients do compared not even to include the trials enrollmentpatients practices, compared in silico drugto the relatively short but expensive market is driven by the same key triggers as trend and invest heavily in R&D of anti-ag- relatively short but expensive treatment development and many other areas. Such treatment courses for diseases like cancer. global healthcare sector like the increasing ing products aiming to capitalize growing the enormouscourses markets for diseases for age-related like cancer. diseases Interest- approaches can thus likely increase the number of aging populations, the recovery customer’s interest. However, the market ingly, contrary to more targeted pharma- overall effectiveness of Big Pharma while such as cancer, diabetes, Alzheimer’s, and various Interestingly, contrary to more targeted pharmaceutical of US and European markets from econom- is still in the developing stage and the tar- ceutical markets such as the treatment simultaneously reducing costs. As such, of Hepatitis-C, the antiaging market is the smaller, more bioinformatics and Big ic crisis, and new advancements in technol- get audience may feel skeptical regarding neuromuscular degenerative conditions. Additionally, of markets such as for treatment of Hepatitis-C, the anti- ogy, particularly in tissue engineering, gene new innovative approaches to treatment. so broadly defned, covering a myriad of Data focused companies such as Insilico therapy and stem cell therapy. According to Due to tough regulation and signifcant the $7 trillionmedical spent conditions, per year on that total it is global highly healthcare un- Medicine, Visionaging Genomics market and is Canadianso broadly defined covering a myriad the United Nations report, life expectancy is breakthrough of technology in recent years, likely that one company could develop Cancer and Aging Research Laboratories to increase by 73.7 years by 2018 resulting people are gradually starting to accept in- expenses, annearly all-encompassing half is spent in solution. the senior After (65+) all, yearsmay be future of acquisition medical targetsconditions for Big that it is highly unlikely that one in the number of people over 65 to be about novative methods to ‘managing age’. As such a solution would need to extend the Pharma companies. We may also likely see of a person’s life to help prolong life [11]. As such, the company could develop an all-encompassing solution. 580 million worldwide (10% of global pop- such, the market for health human longevi- healthy lifespan and function over all tis- the entrance of other bioinformatics / Big sues, organs and systems of the human Data analysis companies whose current fo- market for healthy human longevity is enormous. After all, such a solution would need to extend the THE ANTI-AGING MARKET IS SO BROADLY body. It is for this reason that this specifc cus lies in personalized medicine, diagnos- market segment is likely to be a non-zero- tics or Big Datahealthy analysis lifespan outside the and realm function over all tissues, organs DEFINED, COVERING A MYRIAD OF MEDICAL sum game in that companies in the space of biology and medicine since barriers to For forecastingwill rarely purposes, be competing potential directly treatments with each for entry are comparativelyand systems lower. Examplesof the human of body. It is for this reason CONDITIONS, THAT IT IS HIGHLY UNLIKELY other. It is more likely that the discoveries such companies include Personal Genome the preventionand therapiesof age-related developed diseases by each can compa likely- Diagnostics, whichthat hasthis licensed specific data market anal- segment is likely to be a non- THAT ONE COMPANY COULD DEVELOP ny will largely be complementary and de- ysis software and platforms to HLI, Biovista, AN ALL-ENCOMPASSING SOLUTION pendent on the successful interventions Pathway Genomics, Foundation Medicine, provided by other companies. and Enterra Solutions among many others. 16 | Big Data in Aging and Age-related Diseases 16 Executive Summary Analysis of the Anti-Aging Market 17 Calico Life Sciences, LLC (Calico)

Botstein, a prominent geneticist, former director of the Lewis- Sigler Institute for Integrative Genomics at Princeton University, and former VP of Science at Genentech, and VP Aging Research Cynthia Kenyon, a pioneer in the field of aging research, founder of Elixir Phar- maceuticals and a UCSF Distinguished KEY PERSONNEL Professor of Biochemistry and Biophys- ics and President R & & D Hal Barron, Arthur Levinson, PhD. – CEO, Founder former Executive Vice President, Head Hal V. Barron, M.D. – President R & D of Product Development and Chief Med- David Botsein, Ph.D. – CSO ical Officer at Roche. Cynthia Kenyon, Ph.D. – VP, Aging Research Calico’s stated goal is to harness ad- vanced technologies to increase our understanding of the biology that con- BACKGROUND trols lifespan in order to devise interven- tions that enable people to lead longer Calico is an independent R & D biotech and healthier lives. Calico has since company established in 2013 by Google received an investment of $250 million Inc. and CEO Arthur D. Levinson. In addi- dollars from the pharmaceutical com- tion to Levinson, who served as CEO of pany AbbVie. Additionally, AbbVie has Genentech, as a director of Google and the option to contribute an additional Roche and is chairman of the board of $500 million dollars at a later date. Both Apple, Calico’s other principals form an investments will be matched by Google; COMPANY impressive group including CSO David making this deal worth a possible $1.5 PROFILES

18 Executive Summary Analysis of the Anti-Aging Market 19 billion dollars. Calico has agreed to be called P7C3s, which appear to protect under which Calico will develop and com- ANALYSIS responsible for research and early de- nerve cells in the brain from dying by ac- mercialize compounds resulting from the velopment during the first five years tivating an enzyme called nicotinamide research program. Additionally, Calico will Calico possesses an almost unparalleled and continue to advance collaboration phosphoribosyltransferase that inhibits fund academic and industry research lab- leadership team from biotech, pharma projects through Phase 2a for a ten- cell death. The P7C3 compounds, dis- oratories to support the program. and the ICT industries. This will serve year period. AbbVie will support Calico covered in 2010 by researchers at Uni- them well in building the company from in its early R & D efforts and following versity of Texas Southwestern in Dallas, the ground-up. As such, there should completion of Phase 2a studies and have been tested in numerous models of STRATEGY be few or no barriers that often prevent activities. Both parties will share costs neurodegenerative diseases associated innovation within larger organizations. While Calico has not publicized their strat- and profits equally. with aging, including Alzheimer’s and Par- This should allow the installment of a egy, it can be assumed that Calico is aim- kinson’s disease. The P7C3 compounds new, creative culture to foster scientifc ing to obtaining technologies or platforms In another announcement, the Calico re- were previously licensed to Dallas-based progress and innovation. This new cul- to build the best discovery & development vealed one of its frst development areas: 2M Companies. In a new deal, 2M and Cal- ture should be able to attract many of the platform possible. Its alliance with AbbVie drugs related to a class of compounds ico have entered into a license agreement best and brightest. It is anticipated that shows Calico is serious about developing Calico will likely try to attract academic marketable products to tackle major dis- principal investigators (PIs) in a manner eases in a reasonable timeframe. With SWOT ANALYSIS OF CALICO LIFE SCIENCES LLC similar to the recruitment of PIs at Ge- the backgrounds of its CSO (David Bot- nentech. In this somewhat uncommon stein) and VP-Aging Research (Cynthia arrangement, PIs are given great fexibil- STRENGTHS: WEAKNESSES: Kenyon), Calico may be planning to use ity and independent budgets to pursue model organisms such as worms, mice, • All-star leadership team • Use of model organisms may not translate to the company’s goals. or yeast either to identify age-related ther- • Scientific / Data Expertise therapeutics for humans apeutic targets or as phenotypic readouts Calico also possesses substantial fnan- • Well funded & collaborating with • Lack of focus, no concrete business plan for screening various compounds. If this cial resources that enable them to oper- is the case, subsequent testing will likely credible companies • Collaboration with academic groups increases ate largely independent of fnancial con- need to be performed in specialized mice • Ability to attract the best & brightest organizational complexity straints, unlike VC-backed start-ups. This or rats. Additionally, with their deal with is an immense advantage in light of the • Virtually unlimited financing • Many other non- and for-profit organizations are UT Southwestern [12], it can be presumed exploding cost for a drug to be brought that testing of P7C3s either in mouse / • High visibility pursuing Bell Labs model with limited success to market, estimated to be up to $5 Bil- rodent models of Alzheimer’s and Par- lion dollars. OPPORTUNITIES: THREATS: kinson’s disease or in humans is likely in the future. Calico has also stated that it • Largely unexplored field • Complex FDA regulatory hurdles for anti-aging intends to work with both industry and ac- • Ability to attract collaborators / investment therapeutics ademic labs to further knowledge of the • Ability to drive industry and regulatory framework • Possible failure of P7C3 drugs in pre-clinical or mechanisms governing age-related con- ditions and aging itself. • Ability to make acquisitions and attract best clinical trials people • “Friends of Levinson” approach to hiring and lack of • Ability to recruit Best of Google or attract them young dynamic managers may result in long-term to spend their 20% on Calico’s projects organizational problems and affect Calico’s ability to adapt and change

TABLE 1: SWOT analysis of Calico Life Sciences LLC

20 Executive Summary Analysis of the Anti-Aging Market 21 genome, microbiome and tumor se- cell function, monitor them in real time quencing from consenting UC San Di- and correct any drift from optimal ac- Human ego research patients [11], Metabolon tivity with therapeutics or potentially, Inc., a leader in the field of biochemical stem-cell therapy. This initiative is to be biomarker discovery and profiling field headed by co-founder Robert Hariri, a Longevity, Inc. (HLI) [11], CorTech Labs [13], for its advanced founder of Celgene and the discoverer imaging and image processing capabil- of placental stem cells. In fact, HLI has ities, and Personal Genome Diagnostics stated that it intends to embark on a pro- for its software analysis platforms [14]. gram to monitor the genomic changes which occur during stem cell differenti- ation, normal aging, and in association STRATEGY with the onset of disease. HLI’s agree- ment with Celgene regarding the PSC- the X PRIZE Foundation and Co-Found- HLI’s strategy is to build the largest and 100 proprietary placental-stem cell pop- er/Co- Chairman of Planetary Resourc- most comprehensive database linking ulation likely furthers this strategy. HLI es. To date, HLI has publically raised human genotypes, microbiomes and can also use this stem cell population $70 million dollars from a small group phenotypes. Using this database, HLI as an advanced basis for testing poten- of strategic investors that includes hopes to be able to use Big Data types tial cell therapies for diseases such as Malaysian billionaire K.T. Lim, Bryan of analysis to discover the genetic and Johnson, Illumina and Celgene. Indus- molecular basis underlying disease and EXPLAIN YOUR BUSINESS MODEL try insiders have suggested that HLI in aging. In order to facilitate this type of fact has raised $90 million, of which KEY PERSONNEL analysis, HLI has hired Franz Och, the HLI’s business is focused on several core areas–genomics $40 million has already been spent on former head of Google Translate to be and microbiome analysis and stem cell therapeutics. sequencing infrastructure. It is expect- its new Chief Data Scientist. Addition- J. Craig Venter, Ph.D. – CEO, Founder ed that this initial investment will allow GENOMICS ally, HLI has also partnered with Per- Led by HLI co-founder, Dr. Venter, HLI is building the Robert Hariri, M.D. Ph.D. – Founder the company to continue through May. sonal Genome Diagnostics, Inc (PGDI). largest and most comprehensive human genotype and Peter Diamandis, M.D. – Founder HLI is currently working on raising a Se- PGDI offers several analysis software phenotype database. To do this, the company has ries B round totaling over $500 million and platforms for analyzing cancer and purchased two Illumina HIS-eq X Ten Sequencing Systems before May at a target valuation of $2.1 oncology data including the CancerSe- (with options for three more systems) to sequence up BACKGROUND billion. HLI intends to focus on identify- lectTM, PlasmaSelectTM, CancerX- to 40,000 human genomes per year, with plans to scale ing therapeutics that target age-relat- omeTM, METDetect™, PGDx Enterprise rapidly to 100,00 human genomes. Along with the HLI is a genomics and cell therapy com- ed human biological decline, including, Solution platform and CancerCom- genomic data gleaned from sequencing, HLI will also be pany founded by J. Craig Venter a hu- diabetes and obesity, heart and liver plete™ software packages. From such generating microbiome data, metabolomic and proteomic profiling to provide an unprecedented dataset. man genome pioneer, founder and diseases, and dementia. In order to ac- analysis, HLI intends to commercialize CEO of the J. Craig Venter Institute, complish these goals, HLI has signed therapies for diseases that are associ- STEM CELLS Celera Genomics, The Institute for Ge- deals with Celgene Cellular Therapeu- ated with the biological and molecular HLI is embarking on an ambitious multi-pronged effort nomics Research (TIGR), and Synthetic tics to license, develop, and co-promote breakdown associated with aging. utilizing stem cell therapy advances to enhance and Genomics. Additionally, HLI is co-found- Celgene’s PSC-100 proprietary placen- improve the healthy life span. Under the direction of Robert ed by former CEO, CSO, chairman and tal-stem cell population in age-related An additional application is to create a Hariri, M.D., Ph.D., HDI will monitor the genomic changes which occur during stem cell differentiation, normal aging, founder of Celgene, Robert Hariri, and clinical indications [3], UC San Diego preventive healthcare model that can and in association with the onset of disease. Peter Diamandis, chairman and CEO of Moores Cancer Center to enable whole take baseline measurements of stem-

22 Executive Summary Analysis of the Anti-Aging Market 23 sarcopenia, a condition associated with service provider providing sequencing aging characterized by degenerative and diagnostic services on demand SWOT ANALYSIS OF HUMAN LONGEVITY INC. loss of skeletal muscle mass, quality, to third parties. It is also possible that and strength. with the economies of scale in the se- quencing market that HLI could direct- STRENGTHS: WEAKNESSES: In order to generate the data necessary ly sell its sequencing and phenotyping • Successful leadership • Brute-force sequencing approaches may not be fruitful for these initiatives, HLI has purchased services directly to consumers similarly • Ability to easily raise additional funds at • No concrete business plan two Illumina HiSeq X Ten Sequencing to companies such as 23andMe or An- • Extremely high uncontrollable burn rate Systems (with options for three more cestry. In fact, HLI recently agreed with unprecedented valuations systems) and two PacBio RS II DNA Se- Genentech to sequence tens of thou- • Partnered with credible companies & investors • History of disregard to conventional investor quencing Systems to sequence up to sands of de-identified clinical samples • High visibility interests (Celera) 40,000 human genomes per year, with at 30x sequencing coverage [16]. It has • Unprecedented valuations plans to scale rapidly to 100,000 human even been rumored that HLI may con- • Ability to attract the best & brightest genomes. HLI’s end goal is to sequence sider opening clinical centers focusing • Focus on humans • Recent supercentenarian genome studies and over 1 million full human genomes and on preventative medicine with 7-Tesla • Viable business model catering to Big Pharma Ashkenazi genome studies failed to yield clinically- microbiomes [11]. These will then be ultra-high-field magnetic resonance im- • Ability to think and act Big relevant results compared with matched MRI body-im- aging (MRI) capabilities. age scans using CorTech’s advanced • Rapid growth with many ambitious managers imaging platform, and metabolomes creates rivalry and barriers before there is revenue provided by Metabolon (the current ANALYSIS agreement is to profile 10,000 subjects to map the changes in small molecule While parts of HLIs strategy can be OPPORTUNITIES: THREATS: populations to end points of disease pieced together from publically avail- • Largely unexplored field • Competition from institutions (e.g. Broad Institute, and gene mutations). able information, HLI is currently in an exploratory mode with no clear busi- • Unprecedented integration of large-scale Wellcome Trust, BGI, 100k Wellness Project, The While HLI certainly intends to profit from ness plan guiding HLI’s operation. Si- heterogeneous data types; more likely to find Resilience Project) generating publically available the development of novel therapeutics multaneously, HLI is spending immense actionable associations data and others (Illumina) and diagnostics developed internally or amounts of money in establishing the • Economies of scale will lower sequencing / • Privacy / regulatory concerns from Big Data with partners, it is likely that it will also expensive sequencing and phenotyping attempt to gain revenue from licensing infrastructure required to implement phenotyping costs analysis of patient data its database to pharmaceutical, biotech- their vision. However, it is likely that • Focus on microbiome provides actionable data • Regulatory concerns regarding clinical applications nology, insurance companies, hospitals, with the reputations of HLI’s principals • Potential “Sequence your genome” provider • Big Pharma may not view HLI as an acquisition and academic organizations. An exam- and HLI’s high visibility in the industry ple of such an approach is 23andMe’s that raising any additional funding from • Excellent international network provides opportunity target due to extremely high operational costs recent agreements with venture capital and pharmaceutical in- to establish presence in other countries • In absence of serious revenue, high operational vestors is unlikely to be problem in the Genentech and Pfizer [15]. costs may result in poor financial performance and near future. • Potential to influence government policy It is also possible that with its large loss of investor hype sequencing and molecular profiling ca- While the Big Data style approach taken • “We do everything” approach and heavy focus on by HLI may well prove to be very fruitful pabilities, HLI can also function as a sequencing may fail to yield a sustainable business model

• Possible patient liability (stem cells)

TABLE 2: SWOT analysis of Human Longevity Inc.

24 Executive Summary Analysis of the Anti-Aging Market 25 in identifying targets for therapeutics, 100,000 individuals by 2017 to better it remains possible that most of the understand cancer and other diseases “low-hanging fruit” have already been [17], the Beijing Genome Institute has Insilico taken. There is some minor talk in ac- previously announced its “3M” initiative ademic and industry circles that addi- to sequence 1 million human genomes, tional brute-force sequencing may not 1 million microorganisms and 1 mil- Medicine (ISM) be the most cost-effective way forward lion plants and animals [18], the 100k to identifying additional pathways and Wellness Project to collect and analyze mechanisms to target various diseases. genomic, metabolomic and clinical in- Their argument is that more data will formatics data [19] and The Resilience not necessarily be helpful, but rather a Project which plans to screen hundreds better understanding of how to analyze of thousands of patients to identify mu- and interpret this data is what is need- tations that are protective against other and data management system that ana- ed. In fact, many previous academic already identified deleterious mutations lyzes the genetic, epigenetic, and molec- and industry efforts have gone towards [20]. ular profiles of normal and tumor cells approaching this problem in similar that they refer to as the OncoFinder. fashion, albeit not often at the scale pro- The OncoFinder approach, along with posed by HLI. Additionally, HLI may face its application to normal aging, Age-re- some threat from academic institutions lated Macular Degeneration (AMD), Pro- and other industry players already heav- geria and cancer has been published in ily committed towards increasing their KEY PERSONNEL several academic journals (e.g. [22,23]). own sequencing efforts. In fact, the UK OncoFinder identifies which pathways and Illumina have recently announced Alex Zhavoronkov, Ph.D. – CEO, Founder and gene perturbations are most like- that they will sequence the genomes of Qingsong Zhu, Ph.D. – COO ly to turn normal cells into cancer, and Gene Makarev, Ph.D. – VP, Aging Re- then predict which annotated drug com- search pounds, small molecules and biologics Alex Aliper, Ph.D. – Director of Drug could reverse this process or mimic Discovery various signaling states making cancer more susceptible to therapy. BACKGROUND ISM has further developed a drug discov- Founded in 2013 by Alex Zhavoronkov, ery and repurposing platform that they re- Insilico Medicine (ISM) specializes in fer to as GeroScope that instead of analyz- taking a computational approach to ing normal and cancerous cells evaluates pharmaceutical development. The com- differences in signaling between “young” pany is a result of a multi-year research and “old cells and tissues and simulates project in signaling pathway activation the activity of thousands of known drugs differences between healthy tissues and drugs combinations on differential and cancer by a large international team signalomelevel patterns and assigning funded with over $2.5 million in non-di- the “geroscores”. Thus, analogously to lutive financing. ISM in conjunction with OncoFinder, a computational simulation its main research and business partner can be performed to determine which Hong Kong-based Pathway Pharmaceu- drug compounds might be viable anti-ag- ticals [21] has developed an algorithm ing therapeutics.

26 Executive Summary Analysis of the Anti-Aging Market 27 While focusing on generating revenue combinations of therapies that may have form. This will likely be used both in terms obtain relevant sequencing, expression from partnerships with Big Pharma, Insil- benefcial synergetic effects. Many of of discovering potential novel therapeutic and phenotyping data to build, test and ico Medicine’s research team is dedicated these interventions are likely to be known strategies, as well as attracting additional train its algorithms. In this light, a com- to aging research. Several team members drugs that may be repurposed as antiag- investment and partnerships with pharma- pany like HLI might be an ideal partner including the CEO refuse to take salary be- ing therapeutics or other chemical entities ceutical companies. for ISM since it plans on generating all fore achieving proftability in order to hire a that have enough data to be analyzed by of these types of data on its own and is larger number of research scientists. The the system. As such, ISM is focusing on Despite these successes, ISM may still already investing in analysis capabilities. CEO of the company has extensive expe- cancer, Alzheimer’s and Parkinson’s dis- have lower visibility in the industry due However, with ISM’s low costs and prov- rience in both high-performance comput- ease, atherosclerosis, fbrosis, age-related to the public media frenzy surrounding en expertise, it is well positioned to capi- ing and genomics and is one of the early macular degeneration (with Vision Ge- the entry of Calico and HLI into the mar- talize on this growing industry. Like other evangelists of applied aging research and nomics) and multiple sclerosis. Another ketplace. This may become problematic, bioinformatics focused companies, ISM personalized research. source of revenue for ISM will come from as the largest threat to ISM may be po- is susceptible to competition from oth- licensing GeroScope / OncoFinder to other tential diffculties in fnding partners with er bioinformatics / Big Data companies organizations or partnering to further de- Big Pharma companies. ISM’s strategy since barriers to entry for the feld are STRATEGY velop the software for other diseases and largely relies on such partnerships to relatively low. conditions. In fact, ISM has announced ISM’s long-term goal is to partner with partnerships with Vision Genomics to ap- pharmaceutical and biotechnology com- SWOT ANALYSIS OF INSILICO MEDICINE ply its software to eye-related diseases, panies in order to analyze their patient, and with Canadian Cancer and Aging Re- drug and compound data. ISM believes STRENGTHS: WEAKNESSES: search Laboratories. that with the use of GeroScope, it can ac- • Published expertise in applying algorithms to analyzing • Lower visibility in industry curately predict the effcacy of a drug on cancer data Industry insiders have indicated that ISM is • Large R&D and clinical base outside the United States both individuals and groups of patients, • Proprietary database of healthy norms close to closing a $3.2 million dollar round • Broad geographic spread and possibly improve enrollment in clini- at a $40 million valuation before March • Very dynamic team of young scientists • Limited access to capital cal trials. ISM will also aim to perform in 2015 after receiving a $800 thousand dol- • Large and rapidly growing number of academic • Too many academic publications make it easier for silico simulations on drugs currently in lar convertible loan and is actively hiring publications a pharmaceutical company’s pipeline to competitors to replicate its platforms personnel in Basel, Switzerland to open a • Partnerships with other companies / academic groups predict their effcacy and/or rapidly de- • Competing research teams within Big Pharma local offce. Additionally, ISM is rumored velop companion biomarkers to improve • Focus on actionable human clinically-relevant data to be nearing milestone deals with two clinical trials enrollment and outcomes. • Bioinformatics (low costs) large pharmaceutical companies on drug In this way, companies can better identi- • Located at Johns Hopkins University repurposing and is working on developing fy potential candidates for further study a new joint venture with Israel. and eliminate potential dead ends before THREATS: costly clinical trials. OPPORTUNITIES: • Difficulty finding additional Big Pharma partners ANALYSIS • Pioneer in a growing industry • Difficulty obtaining data to build / test algorithms Additionally, many large pharmaceuti- • Drug repurposing could be lucrative • Possible theft of vital data cal companies have broad portfolios of ISM, in conjunction with Pathway Phar- • Strong relationship with large pharma • Potential competitors from Big Data drugs, some of which may be repurposed maceuticals has published several journal • Sustainable business model with focus on aging to combat or prevent specifc agerelated articles on the use of its pathway analysis • Possible instability in Eastern Europe, China and Israel • Ability to license IP to disease-focused R&D companies diseases. ISM’s platform will be deployed software, OncoFinder. Additionally, with to predict which drugs may be repurposed deals with Vision Genomics and Canadian • Access to Big Pharma databases will help enrich its and how they will behave in various hu- Cancer and Aging Research Laboratories knowledge base man tissues. The GeroScope approach in place, ISM is well positioned to exploit • Alternative applications for pathway analysis and drug can also be used to investigate potential its bioinformatics and data analysis plat- scoring algorithms • Possible acquisition by pharma or software giants

TABLE 3: SWOT analysis of Insilico Medicine

28 Executive Summary Analysis of the Anti-Aging Market 29 outcomes and reduce the costs associat- to the types of data necessary to fulfll this ed with cancer treatment therapy. CCARL vision. Additionally, its relative low visibility Canada Cancer is expected to start clinical trials of a diag- may present a problem in raising addition- nostic test in Canada in May 2015. It can al funding from venture capital investors. be inferred that CCARL will likely need to However, the Canadian government has and Aging Research either provide or partner with other orga- given its support to helping develop the nizations to provide sequencing and mo- nascent biotechnology industry through lecular profling capabilities to feed into Genome Canada to implement a nation- Laboratories, algorithms similar to OncoFinder. CCARL al strategy for supporting large-scale re- is also likely to seek out Big Pharma or ac- search projects in genomics and proteom- Inc (CCARL) ademic partners to obtain and mine their ics. It is possible that CCARL could fnd datasets for potential diagnostic biomark- support from Genome Canada towards ers for diseases and age-related condi- using its approaches to understanding tions of interest. disease. Like other bioinformatics focused companies, CCARL is susceptible to com- cians and to clinical institutions looking petition from other bioinformatics / Big to improve the outcomes and reduce the ANALYSIS Data companies since barriers to entry for costs associated with cancer treatment the feld are relatively low. therapy. CCARL envisions using tools As CCARL plans to develop and deploy like OncoFinder to analyze the genetic algorithms to discover therapeutics for KEY PERSONNEL backgrounds of individual patient tumors diseases and age-related conditions, CCA- and use this information to better select RL’s main diffculties may be in fnding ex- Olga Kovalchuk, M.D., Ph.D. – CEO, and predict the effectiveness of selected ternal Big Pharma partners. Without such Founder therapies. CCARL has also announced partnerships, CCARL will not have access Igor Kovalchuk, M.D., Ph.D. – Founder that Insilico Medicine has invested in a joint collaboration with CCARL to devel- op tools analogous to OncoFinder that SWOT ANALYSIS OF CANADIAN CANCER AND BACKGROUND can detect tissue-specifc epigenetic AGING RESEARCH LABORATORIES changes in disease and aging process- STRENGTHS: WEAKNESSES: The Canada Cancer and Aging Research es [24]. It is hoped that this will lead to • Bioinformatics (low costs) • Low visibility in industry Laboratory (CCARL) was launched in advances in both disease treatment and • Partnerships with Insilico Medicine, University October 2014 by Olga Kovalchuk, a Pro- prevention. Such tools would target the • No relevant publications using stated approach to fessor, Board of Governors Chair in Can- personalized medicine space in the area of Calgary, University of Lethbridge, Pathway multiple sclerosis cer and Canadian Institute of Health Re- of metagenomics and various age-relat- Pharmaceuticals, Plantbiosis, etc • No Science Advisory Board search Chair in Gender and Health at the ed conditions such as leukemia, multiple • CEO represented Canada at World Economic • Difficult interim path to revenue University of Lethbridge and Igor Koval- sclerosis, Parkinson’s disease. Forum and is 40 under 40 women of influence in • Economic weakness in Alberta due to low oil prices chuk, a Professor and Board of Gover- Canada nors Research Chair in Epigenetics at the • No sizable sales team for cancer research tests University of Lethbridge. CCARL aims to STRATEGY THREATS: use Big Data type analysis to improve de- OPPORTUNITIES: cision-making in cancer care by person- While very little is currently known as to • Potential Canadian government support of • Difficulty finding Big Pharma partners in Canada alizing therapy for each patient. To this CCARL’s strategy, they have previously nascent biotech industry • Difficulty obtaining data to build & test algorithms end, CCARL has licensed Insilico Med- stated that they intend to provide deci- • Largely untapped clinical support role • Possible research program cuts in Canada icine’s OncoFinder platform [24] to pro- sion-support services to physicians and to vide decision-support services to physi- clinical institutions looking to improve the TABLE 4: SWOT analysis of Canada Cancer and Aging Research Laboratory

30 Executive Summary Analysis of the Anti-Aging Market 31 market, VG is also likely to try to part- likely help its visibility with pharma- ner with Big Pharma companies with ceutical companies. Additionally, since Vision Genomics, FDA-approved AMD drug treatments in VG has decided to focus on eyerelated order to gain access to their databas- diseases and in particular AMD, there es of clinical data. These companies is likely extensive data that can be ana- LLC (VG) include Genentech (Lucentis), Novartis lyzed using VG and ISM’s approaches. (Lucentis and Visudyne), Pfizer (Macu- Like other bioinformatics focused com- gen), Regeneron Pharmaceuticals (Ey- panies, VG is susceptible to competition lea), and Bayer Healthcare (Eylea). from other bioinformatics / Big Data partnered with Insilico Medicine (ISM) companies since barriers to entry for the to develop a version of OncoFinder spe- feld are relatively low. ANALYSIS cifically for AMD, called AMD Medicine [25]. Note that both Alex Zhavoronkov As VG plans to develop and deploy al- and Evgeny Makarev of ISM serve on the gorithms to discover therapeutics for Scientific Advisory Board of VG. Simi- eye-related diseases such as AMD, VG’s larly to OncoFinder, the AMD Medicine main diffculties, like CCARL and ISM, KEY PERSONNEL platform uses a database of drugs with may be in fnding external Big Pharma known molecular targets and effects on partners. Without such partnerships, VG Antonei Bejamin Csoka, Ph.D. – gene expression in a variety of tissues will not have access to the types of data Founder and CEO and cell lines along with ocular disease necessary to fulfll this vision. However, Naina Bhatia-Dey, Ph.D. – Aging specific gene expression, genetic and its recent publications on AMD should Research & Progeria program epigenetic data. The goal is to use an al- Susan Stair, Ph.D. – General Counsel gorithmic approach to screen for drugs and Corporate Secretary that minimize the differences between SWOT ANALYSIS OF VISION GENOMICS Richard E. Gordon III – Research Asso- healthy and disease states. ciate STRENGTHS: WEAKNESSES: Riya R. Kanherkar – Research • Credibility from AMD and Progeria publications STRATEGY • Low visibility in industry Associate, Public Relations • Bioinformatics (low cost) • Difficult interim path to revenue Little is known regarding VG’s market • Partnerships with Insilico Medicine and Pathway • Likely lack of management experience in a team BACKGROUND strategy. What is currently known is that Pharmaceuticals lead by laboratory scientists the company wishes to apply a Big Data • Clear focus on Age-related Macular Degeneration Vision genomics (VG), is a biotechnolo- approach to produce therapeutics and (AMD) makes a compelling case for investors not gy-based company founded by Antonei pathway knowledge relating to age-re- interested in pure aging research Csoka, an Assistant Professor of Anat- lated eye diseases. Towards this end, omy at Howard University. The compa- the company is developing a special- OPPORTUNITIES: THREATS: ny focuses on the research and devel- ized version of OncoFinder called AMD • Large amount of AMD clinical data available from • AMD therapeutic market is well developed; few

opment of therapeutics for age-related Medicine. They will use this software Big Pharma “low-hanging fruit”? eye diseases. In particular, Vision Ge- similarly to ISM to examine potential • Eye-related diseases are a huge market with • Difficulty finding Big Pharma partners nomics has chosen to primarily focus drug repurposing. This approach has already successful drug repurposing • Difficulty obtaining data to build / test algorithms on Age-related macular degeneration already had some success as several (AMD), the leading cause of visual im- drugs on the market for AMD were re- • AMD seems to be one of the most age-related • Potential competitors from Big Data pairment and blindness worldwide. In purposed from other diseases. Since diseases

order to study this disease, VG has also VG is specifically focusing on the AMD TABLE 5: SWOT analysis of Vision Genomics

32 Executive Summary Analysis of the Anti-Aging Market 33 transduction scoring algorithm. Simul- and their differentiation potential. One of taneously Atlas developed its unique the promising directions is drug discov- Atlas Regeneration pathway analysis scoring platform Re- ery, personalized regenerative medicine, generation Intelligence which utilizes and pharmacology, based on genetic transcriptomic, proteomic and epigen- and epigenetic profle of the patient. At etic data to calculate the potential of this moment, company is utilizing a new signaling pathway activation or actual machine learning approach in chemin- pathway activation score. Based hese formatics to facilitate drug discovery of results, the Atlas team demonstrated candidate drugs able to suppress previ- The project “Atlas Regeneration” began the close resemblance of iPSCs with ously identifed pro-fbrosis pathways. after meeting a famous scientist and ESCs at the pathway level, and provid- STRATEGY director of The Wake Forest Institute ed examples of how pathway activity for Regenerative Medicine (WFIRM) analysis can be applied to identify iPSC The goal of Atlas’ business is to develop Anthony Atala with a team of bioinfor- line abnormalities or to predict in vitro the market and sell novel bioinformatics matics from InSilico Medicine Inc, a differentiation potential. The results in- technologies and services that address successful Baltimore based company dicate that pathway activation profiling the unmet needs of the Regenerative focused on development different path- is a promising strategy for evaluating Medicine market. Atlas team hopes way analysis algorithms and drug re- the safety and potency of iPSC lines in that their algorithm will help to find per- KEY PERSONNEL purposing. As a scientist and practicing translational medicine applications, al- sonal drug combinations for individual physician, Anthony Atala was looking lowing scientists to test differentiation patients and for individual cases (e.g. Eugene (Gene) Makarev, Ph.D. – CEO, for bioinformatics support for his re- abilities of many iPSC lines in silico oil burns vs. water burns). Also Atlas Founder generative medicine programs because while saving valuable time for patients Regeneration wants to personalize cel- Anthony Atala, Ph.D. – Director of Re- there are occurring problems with the waiting for treatment. This work lead lular therapies to the patient- and tis- generative Medicine cell differentiation capacity and cell to first company publication in “Onco- sue-specific microenvironment. From Kristen Fortney, Ph.D. – Director of Bio- therapy safety but no in silico assays target” journal: “Quantifying signaling the other side, its approach can provide informatics to address it have been developed so pathway activation to monitor the qual- the ability to test the pathway activation Oles Isayev, Ph.D. – Director of Drug far. This meeting originated the idea of ity of induced pluripotent stem cells”. profiles in cells provided by contractors, Discovery creating a special bioinformatics tools and in silico prediction of the effects of Dmitry Muhkin, Ph.D. – Director of Busi- to utilize multi-omics data for the needs In 2015 Atlas has partnered with InSili- the various drugs on specific tissues. ness Development of regenerative medicine. co Medicine to build the state of the art PharmAtlas platform to select and to Using pathway based target identifica- tion and in silico drug discovery, Atlas First of all Atlas created a new propri- rate personalized anti-fibrogenic ther- could license this preclinical data to etary database of almost 3 hundreds apies and to identify new drug candi- BACKGROUND pharmaceutical companies. It is a big linearized maps of cell signaling path- dates in regenerative medicine, since it effort for pharmaceutical companies to ways related to regeneration. Each was necessary to find some new way of Atlas Regeneration Inc, a company ded- conduct the preclinical studies of dozed pathway was manually re-curated to regulation and control cells at the mo- icated to developing novel software new drugs and molecules without any meet highest quality standards (to con- lecular level. platforms and algorithms for drug dis- idea of its safety and toxicity in humans covery relating to regenerative medicine tain constantly updated information While at the seed stage, Atlas offers because of huge funding and time ex- and stem cell research, was established based on current literature) and to fit commercial services to other compa- penses and risks. But, with Atlas Re- in 2014. to innovative logic of the Atlas signal nies for evaluation safety of iPS cells generation algorithmic solution it could

34 Executive Summary Analysis of the Anti-Aging Market 35 get cheaper and faster to find the right tion abilities of many iPSC lines in silico Another angle of company specializa- systems that will cost-effectively pre- active ingredient and test drugs on the while saving valuable time for patients tion is screening and predicting the dict the effectiveness of the many preclinical stage. waiting for treatment. effectiveness of possible regenera- drugs on individual tissue, organ and tion-inducing drugs in a high-through- organism levels. And still there are few Despite the costs for drug development, ANALYSIS put environment to at least slow some players which already operate on this not only pharmaceutical companies can of the aging processes by stimulating market and Atlas needs to compete afford it, but there are many institutes Key applications the of Atlas product natural tissues regeneration potential. with them in technological field and in and academia which discover com- PharmAtlas will include quality assur- Some of the known drugs have been on public media as well. Such giants like pletely new substances and therapies ance for engineered cell products and the market for many decades and only Calico and HLI have big names after for various diseases. So Atlas Regener- directed regeneration pharmacology, recently scientists have started finding them like Google for Calico. ation considers this group as potential where Atlas Regeneration will screen clues to their anti-inflammation, re- users of their technology. and identify compounds that can ef- generation and geroprotective effects. ficiently convert pluripotent cells into There is an urgent need for intelligent Besides drugs there is another applica- desired subtypes. Another marketable part of IP is the development of a spe- tion of Atlas Regeneration algorithms. SWOT ANALYSIS OF Atlas Regeneration The team developed bioinformatics cialized signaling pathway analysis sys- tem, Regeneration Intelligence, which algorithm which allows or the evalua- STRENGTHS: WEAKNESSES: is supposed to target the unmet needs tion of the differentiation propensity of • Partnerships with InSilico Medicine and Wake • Low visibility in industry iPSCs using corresponding transcrip- of determination and prediction of sig- Forest Institute for Regenerative Medicine naling pathway activation in iPSC and • Competing research teams within Big Pharma tomic date that dramatically reduce • Atlas Regeneration’s innovative product was proposed cost of analysis and evaluation time. It the differentiated counterparts to pave for SBIR FastTrack • Large R&D and clinical base outside the United States the way to govern iPSC differentiation compares large number of cell types to • Bioinformatics (Low Cost) develop in silico tools to assess tumor- in the specified direction. Aging is an issue that effects all people around • Exceptional knowledge base and experts of leading genecity. Using the proprietary pathway minds in regenerative medicine, bioinformatics analysis system, Atlas Regeneration the globe universally, but as the baby and drug discovery demonstrated the close resemblance boomer generation ages, the stress that it places on society becomes greater of iPSCs with ESCs at the pathway lev- and the need to develop methods for el, which allows them to use ESCs as a OPPORTUNITIES: THREATS: people to remain productive as they age metric for iPSCs cell fate prediction and • Diversification multiple approaches of using Atlas • Difficulty finding additional Big Pharma partners provided examples of how pathway ac- rises in turn. The pharmaceutical indus- allows developing business in a few dimensions try needs a platform to effectively uti- • Potential competitors from Big Data tivity analysis can be applied to identify • Future collaborations with large pharma or academia iPSC line abnormalities or to predict in lize and clinically implement stem cells • Possible instability in Eastern Europe technology. And Atlas Regeneration has • Exploiting new opportunities for existing drugs vitro differentiation potential. Results and their repurposing indicate that pathway activation profil- kind of it, but low visibility in industry ing is a promising strategy for evaluat- may become a problem for finding new ing the safety and potency of iPSC lines partners in pharmaceutical industry or in translational medicine applications, academia. However Atlas has another allowing scientists to test differentia- application of their technology. TABLE 7: SWOT analysis of Atlas Regeneration

36 Executive Summary Analysis of the Anti-Aging Market 37 Conclusion

The amount of funding invested in HLI and Labs-type research institute facilitating col- Calico, based on the quality of the princi- laboration between Google and AbbVie bro- Summary Calico Human Longevity Insilico Medicine Atlas Regeneration Vision Genomics CCARL pal founders of these companies and the kered by one of the top IT and pharmaceuti- hype surrounding these investments, will cal industry veterans. Calico’s choice of mice Announced Sept 2013 March 2014 March 2014 Sept 2015 July 2014 Sept 2014

certainly result in valuable discoveries, in- as a model organism for aging research will Size 10-15 25-35 25-35 15-20 N/A 5-10 (people)* dustry partnerships and attention to the defnitely result in abundant contributions Funding to $250M $70-90M $2.5M + grants N/A N/A <$1M + grants nascent industry. It also turns smaller and to basic research with publications in top-ti- date* leaner companies into attractive invest- er academic journals; however, its ability to OMMER CIALIZING GING ESEAR CH ERIES Valuation $2B ment opportunities. Table 6 providesC a A R generate S revenue is questionable and new $2.2B $40M $4M $1.5M $2.5M Seeking Human Longevity, Inc will generate vast amount of to extend human longevity. In silico geroprotector No Yes, $500M, Round B Yes, $3.2M, Round B Yes Yes, ~$1M, Round A Yes, ~$5M, Round A comparative analysis of the fve compa- intellectual property may be subject to the Funding?* clinically-relevant data that may be licensed to large screening by Insilico Medicine and Bid Data analysis nies covered in this report. right of frst refusal by AbbVie. Depending on Baltimore, MD Winston-Salem, NC Washington, DC Lethbridge, Alberta Location Mountain San Diego, MD pharmaceutical companies, where demand for this effotherts bstructurey Vision Gen oofmi cthes an ddeal, CCAR LAbbVie promise t mayo beneft View, CA kind of data is validated through recent acquisitions deliver first interventions in the very near future if For Calico, should its portfolio of P7C3 neu- from potential upside offered by its newly es- Scientists’ Yeast, worm, Human Genome Seque- Human Transcriptome, Human Transcriptome, Human Transcriptome, Human Genome, (e.g. deCODE) and deals with 23andMe. HLI’s focus their approach comparing changes in specific human roprotective drugs or its $1.5 Billion research tablished R & D center. Strengths mouse models ncing, Microbiome, Stem MicroRNA, Methylome MicroRNA, Stem Cell Epigenome Transcriptome, on human data is encouraging, as any discoveries tissues during aging and disease and correcting Cell microRNA collaboration with AbbVie result in clinical- may be rapidly transitioned into clinical practice. these changes with pharmaceuticals helps identify ly-viable discoveries, it will still be several Human Longevity, Inc will generate vast Business Basic research Database licensing and Drug repurposing, Big Stem cell quality and Drug discovery and Personalized medicine However, it will likely take years before the company safe clinically-proven drugs (Figures 5-7). model in mice, R&D for contract R&D for Big Data R&D for aging, safety, contract R&D for personalizaton for ocular in cancer, R&D in Abbvie, P7C3 Pharma, internal drug contract research for Big Pharma and diseases (AMD and RP), multiple sclerosis, years s beforetarts ge ne revenuesrating reven ue can from beinte r generated.ventions design ed amounts of clinically-relevant data that may neuroprotectors, discovery, clinical large pharma, business academia Drug Progeria, personalized contract R&D for From a commercial perspective, the com- be licensed to large pharmaceutical compa- business services incubation repurposing medicine government and Big pany may be viewed as a well-funded Bell nies, where demand for this kind of data is incubation Pharma Diseases Neurodegenerat N/A Cancer, Aging, Age-related diseases, Age-related Macular Cancer, Multiple ive, Aging Neurodegenerative Cancer Degeneration, Progeria Sclerosis, Aging

Infrastruc- N/A High Low Low Low Low ture investment

Yes Wet N/A Yes Yes N/A N/A Laboratory

Sequencing N/A Illumina X Pacbio CustomArray, Ion Proton N/A N/A Illumina HiSeq/MiSeq, Atlas infrastruc- Systems Regeneration ture Lethbridge Seq Core Software Yes Yes None In development Yes Yes Platform None None None Drugs in the P7C3 class None None Pipeline compounds Low Low Low Burn Rate N/A Very High Low

Industry Yes Yes Yes N/A N/A Yes Deals

Number of None None High High High High publica- tions Licensed from N/A Pending N/A N/A N/A Patents UTS

*Speculation FIGURE 5: Research focus and time to market TABLE 8: Calico, HLI, Insilico, Atlas Regeneration, Vision Genomics, CCARL company summaries N/A – not available

38 Executive Summary Analysis of the Anti-Aging Market 39 Industry Overview | 35 C OMMER CIALIZING AGING RESEAR CH SERIES

validated through recent acquisitions (e.g. in the traditional pharmaceutical in- deCODE) and deals with 23andMe. HLI’s fo- dustries, but also in academia. While cus on human data is encouraging, as any the number and quality of academic discoveries may be rapidly transitioned into research institutes and laboratories clinical practice. However, it will likely take studying aging are dramatically increas- years before the company starts generat- ing, we have also witnessed the cre- ing revenue from interventions designed to ation of specialized graduate programs extend human longevity. In silico geropro- in aging research. Partly funded by the tector screening by Insilico Medicine, Atlas National Institute on Aging, programs at Regeneration and Bid Data analysis efforts the Buck Institute for Aging Research Atlas by Vision Genomics and CCARL promise to / University of Southern California PhD Regeneration deliver frst interventions in the very near fu- Program in the Biology Aging, and the ture if their approach, comparing changes Tulane University Interdisciplinary PhD in specifc human tissues during aging and Program in Aging Studies will greatly ex- disease and correcting these changes with pand the pool of scientists working on pharmaceuticals, helps identify safe clini- aging. This can be expected to enhance cally-proven drugs (Figures 5-7). the science of the aging process and will benefit the inevitable expansion of It is currently only the infancy of the an- the industry with more scientists work- ti-aging therapeutics and longevity in- ing towards creating anti-aging thera- dustry. Similarly to 1910- 15 in the auto- peutics. motive, 1970-75 in the computing, and FIGURE 6: Clinical vs. Basic Science focus 1990-1995 in the networking industries, As evidenced by the recent activity and en- the industry is likely to explode with ac- try of new players to the industry, the fu- tivity in the coming years. The entry of ture of the anti-aging therapeutics and lon- Calico and HLI, along with substantial in- gevity industry is incredibly promising. We vestment and media attention has served will undoubtedly witness signifcant suc- to usher in a new era for the anti-aging cesses towards improving the quality and industry. With a potentially huge market length of human lifespans in the coming for anti-aging therapeutics, we can expect years, ushering in a new era in medicine. to see substantial new investment from established Big Pharma companies as Overall, our forecasts point out to well as the entry of new startups and Big greater prospects for growth of the Data companies into the industry. This is anti-aging industry in 2016 than in already evidenced by the entry of startups the preceding years. Our projections such as Insilico Medicine, Atlas Regen- signal a great expansion in Anti-ageing eration Vision Genomics and Canadian startups. More new entrants will join the market and it certainly entails Cancer and Aging Research Laboratories, the expansion of the total number of and the numerous licensing and research entities that claim to be in the same agreements being signed by companies category while producing substandard such as Genentech and Pfzer. research and subsequent substandard products. We expect investments in Not only has this explosion of activity that sector to grow substantially in the in the antiaging industry been observed coming year. FIGURE 7: Near-term revenue potential vs. access to capital

36 | Big Data in Aging and Age-related Diseases 40 Executive Summary Analysis of the Anti-Aging Market 41 COMMERCIALIZING AGING RESEARCH SERIES

17. MIT Technology Review (2014). British Government idUSnGNX4KpF0L+1d5+GNW20140306 Picks Illumina to Sequence 100,000 Genomes. http:// www.technologyreview.com/news/528946/british- 22. Zabolotneva, AA et al. (2012). Characteristic government-picks-illumina-to-sequence-100000-genomes Patterns of MicroRNA Expression in Human Bladder Cancer. Front Genet. 3:310 18. About.com (2013). BGI Plans to Sequence the World. http://biotech.about.com/od/investinginbiotech/a/ 23. Makarev, E. et al. (2014). Pathway activation Bgi-Plans-To-Sequence-The-World.htm profiling reveals new insights into Age-related Macular Degeneration and provides avenues for 19. Institute for Systems Biology (2014). therapeutic interventions. Aging 6:12, 1064-75 Institute for Systems Bioogy 100K + P4. http:// research.systemsbiology.net/100k 24. PRWeb (2014). Canada Cancer and Aging Research Laboratory (CCARL) Launched in Lethbridge to Provide 20. Icahn School of Medicine at Mount Sinai Personalized Diagnostic and Medical Solutions for (2015). The Resilience Project: A Search for Cancer and Age-Related Diseases. http://www. Unexpected Heroes. http://resilienceproject.me prweb.com/releases/2014/10/prweb12232415.htm

21. Thomson Reuters (2014). InSilico Medicine Inc. 25. Vision Genomics, LLC. (2014). Exclusive Signaling Launches in the US to Use Advances in Information Pathways Discovered for Age-Related Macular Technology to Combat Aging and Age-related Degeneration. http://www.visiongenomics.com/ Diseases. http://www.reuters.com/article/2014/03/06/ research-articles/latest-research-vision-genomics

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42 Executive Summary Analysis of the Anti-Aging Market 43 BIG DATA IN AGING AND AGE - RELATED DISEASES

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