From: jeffrey E. <[email protected]>

From: jeffrey E. <[email protected]> Sent: Tuesda , Au ust 29, 2017 9:58 AM To: Subject: Re: Alzheimer's well done On Tue, Aug 29, 2017 at 1:28 AM, FYI <mailto » wrote: Forwarded mess=ge From: <Bill and Larry - hi. =nd just to you both - I will send to the others and copy Larry later tonig=t. <mailto Given my experience building and manag=ng learning initiatives and my understanding of this landscape, I've t=ied to think about your competitive/comparative advantage while giving you=a little more time to learn in the background. At the end of this learning y=u could exit the space easily, go deeper or even change strategies based o= what you learn. In 2-3 years a few things will unfold - and I would just =aution you to tread lightly because all sorts of new data is emerging - no= only about mechanisms of disease but about whether AD is a distinct patho=ogic entity. Lord knows = I just don't want you to get caught into a=polio type vortex until you are ready. McKinsey has been hired to help build y=ur strategy and I will pass all of this along to the McKinsey team, Bose a=d Jonah under separate cover. I will also continue to support them, make i=troductions and join their sessions - next one September 8. In my honest o=inion, McKinsey maybe not the right partner but we will all rally behind t=em. <=pan style="line-height:115%"> See you both soon... I =font face="verdana, sans-serir> EFTA_R1_01870063 EFTA02638525 Ideas for Transforming the Alzheimer Landscape Asp=ration 1. =/span>Segment the I=ndscape until we have a natural advantage 2. =Opportunitie= small enough to win, large enough to matter 3. <=span>Measurable poi=ts on the board Sit=ation - =C2 Alzheimer =80 s is not a typical disease with a single causal factor / etiology - =C2 Polarized scientific community =C2 No shortage of R&D resources =C2 Requires longitudinal investments in health and hard to quantitatively track patholo=y =C2 What needs fixing <=pan style="font-size:l2pt;line-height:115%">o =AO Institutions — processes, policies <=pan style="font-size:l2pt;line-height:115%">o =AO Tools & technologies — validation, standardization o =C2 Science — exploration, cross-sector ideas Inf=rmed Entry into Alzheimer's Landscape <=ont face="verdana, sans-serif'> $1O0 million, 3 year learning initiative managed quietly from bgc3 that will explore: 1. =/span>Performance o= existing institutions vs. need for creation of new (or hybridized) ones 2. =Opportunitie= for cost savings and market building 3. =Barriers to =linical trial participation 4. =Processes fo= data sharing and standardization 5. <=span>Novel mechanis=ic approaches Spe=ific Targets for Exploration <=ont face="verdana, sans-serif'> 2 EFTA_R1_01870064 EFTA02638526 Target 1: Underwrite risk for private sector; keep data in the public domain $20 mil=ion AMC-AD;National Institutes on Aging (NIA) Matchin= grant (1:2 for government, 1:1 for private sector) Propose= Outcomes <=ont face="verdana, sans-serir>. NIA<=pan> In 3 years, study and trial data for 2016++ pipeline fully public and curated by =font face="verdana, sans-serir>. Stronger NIA =font face="verdana, sans-serir>. Open trial data=/span> 10 new candidate drugs put into later stage discovery process Cost Recipie=t Form Possibl= Partner: IMI Propose= Outcomes <=ont face="verdana, sans-serif'>• In 3 years, 5 validate biomarkers =font face="verdana, sans-serir>. Standardized validation processes =font face="verdana, sans-serif'>• Open and shared trial and registry data Aligned US/Europe regulatory and study processes What we=learn <=ont face="verdana, sans-serir>. Coherence of standards =font face="verdana, sans-serir>. Appetite for shared data Ability of new institution to attract additional resources <=pan> <=ont face="verdana, sans-serif'>Target 3: Build microbiomic fundamentals $20 mil=ion across 3 recipients 3 EFTA_R1_01870065 EFTA02638527 Recipie=t 1. $Sm to NIA/NIH to RFP pre-inflammatory and inflammatory markers ($5m) 2. $Sm to ICDDR,B to classify non-pathogenic colonists and create a digital library <=span> 3. $10m TBC via BMGF to redraw bacterial taxonomy based on genetic criteria to supplement traditional identification and classification<=p> Grants =span> Propose= Outcomes <=ont face="verdana, sans-serif'>• Identify non-pathogenic colonist strains for use in health and also food and supplement indusitry=span> =font face="verdana, sans-serif">• World Gut library Update bacterial classification systems to include genomics<=font> What we=learn <=ont face="verdana, sans-serif'>. Build a deeper understanding of the microbiome with applications across health, pharma a=d food sciences =font face="verdana, sans-serif'>• Modern bacterial taxonomy based on genetic characteristicsq=ont> Microbiome non-pathogenic library offers biomarkers for health but also potential prebiotic and endobiotic candidates for food and pharmaceutical industrie= (monetizable = creates new market) <=pan> <=ont face="verdana, sans-serif'>Target 4: Invest in computational repurposing of failed candidate drugs $18 mil=ion TBC 1. Sim scoping (go/no go) effort with McKinsey 2. $2m pilot 3. $15m initial investment in repurposing fund either as part of a new entity versus with=n the NIA AMP-AD 1 contr=ct, 1 grant and 1 investment Propose= Outcomes <=ont face="verdana, sans-serif'>• Scope potential of market and collaboration with McKinsey =font face="verdana, sans-serir>. 20 repurposed medications Creates new market opportunity for failed drugs 4 EFTA_R1_01870066 EFTA02638528 Target 5: Investigate and build social biomarkers correlated with aging and dementia $2 mill=on Israel =rain Technologies Grant f=r Grand Challenge -style competition What we=learn Scale and scope of potential for digital biomarkers in cognitive disease <=ont face="verdana, sans-serif'>Target 6: Bring the financial industry into the conversation $1 mill=on $1 mill=on to Dr. Jason Karlawish at University of Pennsylvania Medical School / Wharton School <=font> Grant What we=learn <=ont face="verdana, sans-serif">• Possibility of using financial markets to reduce cost and ease burden of care =font face="verdana, sans-serif'>• Create a new financial product =font face="verdana, sans-serif">• Create automated checks and balances or financial standards for demented adults or retiree= over age 65 with cognitive challenges Share actuarial burden between long term facility care-caregivers <=pan> <=ont face="verdana, sans-serif5Target 7: Reduce CMS facility and hospital admission costs $1 mill=on RAND Grant What we=learn <=ont face="verdana, sans-serir>. Save tons of money =font face="verdana, sans-serir>. Reduce hospital admissions Share burden of care 5 EFTA_R1_01870067 EFTA02638529 apan> <=ont face="verdana, sans-serif'>Target 8: Improve trial enrollment<=span> $2 mill=on Lon Sch=eider, USC School of Medicine Grant Propose= Outcomes <=ont face="verdana, sans-serif'>• Linkage across trials =font face="verdana, sans-serif>. Improved (and shared) recruiting tools =font face="verdana, sans-serif">• Corporate advocacy Involvement of search engines (Google, Bing, etc) in stacking searches What we=learn <=ont face="verdana, sans-serir>. Barriers to participation =font face="verdana, sans-serir>. Corporate appetite to contribute Institutional appetite to widen trials and/or share controls=/p> <=pan> cont face="verdana, sans-serif'>Target 9: Novel mechanisms for exploration $25 mil=ion Either =ia intermediary such as Cure Alzheimer's Fund or 8-10 individual recipients (see below)<=span> Grant What we=learn <=ont face="verdana, sans-serif'>• Dysregulation of neural pH dynamics: Aimee Kao, Ph.D. / University of California, San Francisco =font face="verdana, sans-serif'>• Human age equivalency and functional phenotypes: Fred "Rusty" Gage, Ph.D.=/ Salk Institute for Biological Studies =font face="verdana, sans-serir>. Gliovascular changes and waste (glymphatics): Jeffrey Iliff, Ph.D. and William Rooney, Ph.D. / Oregon Health & Science University=/p> =font face="verdana, sans-serif">• White matter dysfunction as a biosensor: Ragnhildur Thora Karadottir, P=.D. / University of Cambridge 6 EFTA_R1_01870068 EFTA02638530 =font face="verdana, sans-serir>. Cellular networks controlling proteinopathy: Martin Kampmann, Ph.D., Michael Keise=, Ph.D., David Kokel, Ph.D. / University of California, San Francisco=/span> =font face="verdana, sans-serif">• Weizmann Institu=e Immunological gating pathways and denegeration: Dr. Michael Schwartz / =font face="verdana, sans-serif">• Rejuvenation of the nervous and vascular systems: Dr. Shai Efrati / Sagol Center Filamentous bacteriophages as therapeutics: Proclara biosciences (may be better fit f=r DDF) <=pan> <=ont face="verdana, sans-serir>Target 10: Convene a 3 year Task Force to guide your learning $ 1 mil=ion NACC, D=. Bud Kukull / University of Washington Grant What we=learn <=ont face="verdana, sans-serif>• Expert opinion(s) on emerging data, trends and science Progress and perspective on our own learning from Targets 1-9 as listed above <=pan> Man=ging the Process $ 500,0=0 per year TBC Contrac=or or Staff (bgC3) as under the radar manager or advisor + .25 FTE administrative support Propose= Process <=ont face="verdana, sans-serif'>• Perform due diligence on proposals =font face="verdana, sans-serif">• Manage portfolio of learning grants (and contracts)</=> =font face="verdana, sans-serif'>. Report to Bose/Jonah/Larry quarterly or as required otherwiseq=ont> =font face="verdana, sans-serif'>• Attend or delegate attendance for major meetings =font face="verdana, sans-serir>. Submit quarterly summary report and annual learning report<i=ont> Serve as primary point of contact with partners / quarterly calls <=ont face="verdana, sans-serir> 7 EFTA_R1_01870069 EFTA02638531 =AO please note The information contained i= this communication is confidential, may be attorney-client privileged,=may constitute inside information, and is intended only for the use =f the addressee. It is the property of JEE Unauthorized use, disclos=re or copying of this communication or any part thereof is strictly pro=ibited and may be unlawful. If you have received this communication =n error, please notify us immediately by return e-mail or by e-mail to =a href="mailto:[email protected]" target="_blank">jeevacation@gmai=.com, and destroy this communication and all copies thereof, inc=uding all attachments. copyright -all rights reserved --001a11493bfe2da53b0557e1711f-- conversation -id 33690 date-last-viewed 0 date-received 1504000661 flags 8590195713 gmail-label-ids 7 remote-id 744229 8 EFTA_R1_01870070 EFTA02638532