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Defeating COVID-19

Fred Brown has extensive experience leading responses to epidemics. He summarizes the COVID-19 pandemic as exceptionally dangerous due to widespread lack of immunity and high contagiousness. Strong social distancing has slowed the virus's exponential growth but devastates economies. Three restoration strategies are suggested: developing a vaccine, allowing herd immunity through widespread infection, or managing social behavior to minimize risk while restoring some economic activity over several years. The last option, a "marathon" approach, is argued to be the safest strategy.

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Defeating COVID-19 Fred Brown 2020 04 05
Where I ve Been ▪ M life o k i defea ing illne and i al e idemic ▪ My epidemic intervention experience includes: Developing and commercializing first test for HIV (Centocor) Developing and commercializing polyvalent vaccines (GSK, Novartis, (many)) Managing Roche Diagnostic andTamiflu suppression of H5N1 Influenza ▪ I have also led 0r supported the discovery, development and/or launch of 27 pharmaceutical, 13 diagnostic and 6 vaccine products saving 5.6M lives per year and achieving combined peak sales of over $35B Global Head, Hoffmann LaRoche Product Lifecycle, Partnerships and Informatics. Co-founder and executive leader of two innovative Life Science companies like Alkermes (NASDAQ: ALKS). ▪ Board Member of Continuing Medical Education - Johns Hopkins Medical School/ES4P 2©2020 Fred Brown
Where I m Coming From ▪ I believe humans are responding too slowly and too narrowly to the scale and speed of the pandemic threat ▪ These are solely my opinions based on my experience and the data available on 4/5/20 These are early days and facts are scarce; beware of certainty (economists, scientists, politicians, pundits, investment advisors, relatives) Government and industry leaders are naturally biased on behalf of their institutions; evaluate their statements accordingly My only interest here is to save lives ▪ I ee m elf a an an igen ing o im la e he o ld imm ne system to respond more robustly to the threat 3©2020 Fred Brown
Goals of This Presentation ▪ To help people think clearly about the huge issues raised by the COVID-19 pandemic You as leaders have the potential to make a real difference; I want you to know the facts and use them: feel free to steal and use this material! Other audiences: scientists, elected officials, journalists, general public ▪ To make it easier to parse the daily flood of information and opinion on the topic ▪ To provide some easy frameworks with signals and indicators to help people determine where we are in this war 4©2020 Fred Brown
What We re Up Against ▪ SARS CoV-2 is an exceptionally dangerous virus We have no immunity: it will take a long time to reach herd effect I highl con agio i co ld infec mo of he o ld a idl I a kille le ing i n i co e o ld be ca a o hic I in a famil of i e fo hich accine a e diffic l o de elo I abili o m a e o e ade accine and an i i al i nkno n ▪ Our world is tailor-made to be vulnerable Our economies depend on global supply chains, pervasive travel, face-to-face service industries, and high population densities in concentrated urban areas We e mo e mobile and mo e ocial han h man ha e e e been befo e Our information environment is ubiquitous, engaging, and unreliable Our politics are polarized 5©2020 Fred Brown
Where We Stand ▪ Since first identified in humans in China in late 2019, COVID-19 has appeared in 184 countries, accounted for 100,000 confirmed deaths, and overwhelmed healthcare systems in China, Italy, Spain, and the US ▪ Hence e e managing a a o la ion le el no an indi id al le el ▪ The only response thus far which has moderated the exponential growth of infections has been strong social distancing, including extreme reductions in travel ▪ Such social distancing brings economies to a near-standstill ▪ The virus itself is impairing our ability to respond because it disrupts our fragile just-in-time systems and global supply chains.This impacts healthcare, pharmaceuticals, medical supplies, and medical equipment 6©2020 Fred Brown
#ofInfected 1 5 30 15 R = 1.25 Influenza Every Day Counts Influenza has a typical infection rate of 1.25. In 30 days from the fi ca e o ll ha e ca e if o don intervene. Days 7©2020 Fred Brown
#ofInfected Days 1 5 30 15 R = 1.25 Influenza Every Day Counts 406 R = 2.5 COVID 19 COVID-19 has a typical infection rate of 2.5. In 30 days from the first ca e o ll ha e ca e if o don intervene. Influenza has a typical infection rate of 1.25. In 30 days from the fi ca e o ll ha e ca e if o don intervene. 8©2020 Fred Brown
#ofInfected Days 1 5 30 15 R = 1.25 Influenza 406 China intervened on Day 12. Had they intervened just SEVEN DAYS EARLIER, they would have cut their 30-day case count in half. Had they waited SEVEN DAYS LATER, they would have let their case count increase nine-fold. The virus attack is exponential. Our responses are linear. Every Day Counts x/2 9x R = 2.5 COVID 19 9©2020 Fred Brown
#ofInfected Days 1 5 30 15 R = 1.25 Influenza 406 Every Day Counts Take-Aways 1. It s better to over-respond to an epidemic early and back off rather than to hope, wait and see it will overwhelm you • COVID-19 reproduces exponentially while our responses are linear • Our traditional processes will not work to control COVID-19 2. Data, Data, Data • Real time, not batch • Granular, broad, and searchable, not siloed 3. Range of uncertainty also increases exponentially over time with no new data R = 2.5 COVID 19 x/2 9x 10©2020 Fred Brown
How Should We Proceed? ▪ Sufficiently strong social distancing collapses infection rates but devastates economies & societies.Three restoration strategies have been suggested: 1. Get lucky. Perhaps one of the first vaccines to be tested will prove safe, effective, and scalable.With a lot of luck, we could arrive at a post-COVID-19 era as soon as late 2021. 2. Get brutal. If allowed to run rampant, this virus might follow the path of the 1918 Influenza epidemic, which eventually died off after killing perhaps hundreds of millions in three trips around the world. It left most of the survivors with immunity, insuring its own demise. 3. Win a marathon. Learn to manage social behavior to minimize risk while restoring some economic activity. Press ahead on antivirals and vaccines with realistic expectations. Innovate to optimize economic benefit under duress. This could last for years. 11©2020 Fred Brown
Getting Lucky: How Lucky Can We Get? ▪ Vaccines against viruses average 13 years to develop ▪ So far, no vaccines exist for any human Coronaviruses ▪ Today there are 78 COVID vaccine candidates under investigation ▪ There is no consensus yet about most likely candidates, an indication of early days ▪ Huge resources have been committed. There is initial coordination between some efforts, but the vast majority remain independent. Regulatory agencies have promised streamlined processes ▪ Odds of getting lucky? Less than 20% ▪ We need a Plan B 12©2020 Fred Brown The costs of a decision could be orders of magnitude higher medically, economically, psychologically and socially if unchecked. Social distance shut-downs have projectable economic and health costs. Unchecked pandemics do not.
Getting Brutal: Betting on Herd Immunity Bet: Total humanitarian costs of shutting down the economy > Total costs of letting coronavirus run its course We are early in this war to make an all-or-nothing decision. We know so little about COVID and are defenseless against it. Leaders have always bought time until they know more about alternatives and true risks of deploying such a strategy. 1. Wild Bet right now we have no idea of the true, eventual downside risk ▪ COVID e fa ali e od c i e and m a ion a e ▪ The range of medical issues it can cause across diverse genetic populations and broader ranges of underlying conditions, ▪ The degree and duration of herd immunity after infection, and ▪ The costs of a decision could be orders of magnitude higher medically, economically, psychologically and socially if unchecked. Social distance shut-downs have projectable economic and health costs. Unchecked pandemics do not. ▪ Until a detection and public health infrastructure is in place to guide deploying a brutal strategy, it could run tragically amok. 2. This bet is all in ▪ A deployment decision is non-reversible and on a hair-trigger. We have no weapons to fight COVID 19 today- unchecked, it co ld infec mo of he o ld o la ion in a ea o o ▪ Healthcare services would be utterly overwhelmed ▪ Total COVID19-related mortality rates worldwide are uncertain, but global deaths on the order of 1 2% of total population 75 to 150 million people in 2021-22 would be a plausible first guess. ▪ Any large mobile population can trigger a brutal pathway that envelops the world. Once initiated, we have no infrastructure to detect or halt the virus. It would run its course unchecked - No do-overs. Nowhere to hide. ▪ This choice is morally, psychologically, and politically devastating ©2020 Fred Brown 13
Welcome to the Marathon: COVID-19 War Games Four Scenarios: 1. Spontaneous Combustion (<1% chance) The virus mysteriously sputters out. It has happened before. 2. Magic Bullet (<20% chance) We get lucky fast with an effective vaccine ~19 months (<20% chance) 3. Therapeutic Cocktails (60% chance) Intermittent social distancing, testing and tracing; and a sequence of improving cocktails and partial vaccines; then an effective vaccine in ~5 years (60% chance) 4. War of Attrition (20% chance) Similar to #3, but on a more typical timeline for development of vaccines, antivirals, and other treatments, leading to an effective vaccine in ~10 years (20% chance) 14©2020 Fred Brown
Welcome to the Marathon: COVID-19 War Games 2020 2021 2022 2026 2027 2028 2029 2030202520242023 Economic & Social Normalcy 95 100% 30-60% 60 75% 75-95% LEGEND Magic Bullet: revolutionary vaccine by Q2 2021, perfect execution, no COVID-19 bounce-back Spontaneous Combustion: COVID-19 quickly sputters out<1% <20% 20% 60% Convalescent Plasma Repurposed Drugs Therapeutics Antivirals PartialVaccine Vaccine Therapeutic Cocktails: behavior management and drug treatments reduce harm and buy time until an effective vaccine takes over War of Attrition: traditional drug and vaccine timelines and failures. COVID-19 may fight back with mutationsConvalescent Plasma Repurposed Drugs Therapeutics Antivirals PartialVaccine Vaccine Vaccine 15©2020 Fred Brown
Winning a Marathon (Full of Sprints) Social Distancing & Diagnostics Drugs Vaccines Time Effectiveness Herd Immunity 16©2020 Fred Brown
Phase Shifts ▪ Phase I Social Distancing & Diagnostics: non-pharmaceutical; requires intermittent strict behavioral constraints: test & trace, social distancing, and mo e AKA bo ing ▪ A third of the economy in any one geography will be turned off at any one time. Unsynchronizable.Governed by adaptive triggering ▪ Phase II Drugs: useful anti-viral cocktail(s) become available to reduce severity, frequency, and mortality of infections which reduces duration and frequency of boxing episodes ▪ Phase III Vaccines: effective vaccine(s) become available at scale (if virus cooperates); vaccines accelerate herd immunity, boxing ends ▪ Within phases, incremental improvements; at phase shifts, bigger jumps 17©2020 Fred Brown
NewConfirmedCases Non OutbreakArea Shutdown 2 Months OutbreakArea Shutdown (Wuhan) 2.5 Months FY GDP 6.1+% FY GDP 3.3-% The First COVID-19 Attack (China): One & Done? 4000 3500 3000 2500 2000 1500 1000 500 0 18©2020 Fred Brown
Or Recurring Attacks Sep 21 Nov 21 Jul 21 May 21 Mar 21 Jul 20 May 20 Jan 21 Nov 20 Sep 20 Mar 20 Trigger: >2.5% of Available ICU Beds Devoted to COVID-19 Boxes = Economy off d e o social distancing and other restrictions Wi ho he a e ic and accine o figh back h man m o imi e ocial di ancing i h ada i e igge ing Herd Immunity? After wave 1, 95% of us remain susceptible. Herd immunity may require 55-85% to have antibodies and may only last for one season. Goal: Make the boxes narrower and farther apart, to keep the economy switched on more of the time. 19©2020 Fred Brown
D Sense and Respond 4 weeks ago 3 weeks ago 2 weeks ago 1 weeks ago Today In 1 week In 2 weeks Exposure Symptoms Resolution 1 Death Infectious 14 days - Number Infected 100 200 400 800 1600 3200 6400 2 Deaths 4 Deaths Clinical Surrogate (Death)TriggerDiagnostic TestTriggers Case Fatality Rate 1% Doubling Time 1Week Shorten the Detection Window VS. • Humans - No counter attack technologies COVID A mame • Long infectious period • Large asymptomatic population • Moderate death rate • Mutation rate stable so far 20©2020 Fred Brown
The Dance of Science and Economics ManageThe Box to Increase Normalcy 1. Narrow the length of economy off by increasing the compliance to distancing measures 2. Reduce the frequency of economy off with improved drugs and diagnostics/tracing control 3. Raise the height of the trigger (adaptively) with improved health system capacity Increase Compliance • Infrastructure • Diagnostics • AI . . . . . . Step 2 Medicines • Therapeutics • Anti-virals • PartialVaccines Economy Off . . . Step 1 Reduce Shut-Down Duration Reduce Shut-Down Frequency 21 21©2020 Fred Brown
Our Phase 1 Weapons 1. Diagnose Surveillance All Crowded Events/Venues Minimum - 128 M tests per week 85% Predictive, Instant, <1c $2.00 PCR/Point-of-Care Accurate ActiveVirus Detection - Minimum capacity 75M tests per week 0.04% False neg. rate, 15 min, $20 -$50 Monitor Antibody Detection Minimum capacity 65M per week 0.01 % False pos. rate, 2 d, $15 - $50 COVID WAZE COVID Expert Bot Contact Tracing &Status National COVID- Registry Global Vaccines Registry 2.Track &Trace • Artifical Intelligence • Expert Systems • Machine Learning • Predictive Analytics Apps 3. Auto-Mitigate Large infrastructure upgrades are required immediately in three areas to support and automate our social distance defenses ©2020 Fred Brown 22©2020 Fred Brown
Manhattan Project Identify, Isolate and Auto-Trace Q2/2020 – Building the New Infrastructure Q3/2021 - Precision Monitoring or Self/Dr. Report Surveillance ContactTracking TEST No COVID 30% 70% Hospital Field Hospital Home (+/- Smart) Quarantine /Isolation COVID Confirmed Triage ClinicVery ill ill Population Sick Asymptomatic Immune Well Low Risk Well High Risk Anti-body Testing For Immunity Vaccine Registry Tracking App - Immune Cert - Test Checks - Location - Result - GPS - O he 43% Telehealth COVID Suspected 5/20 - Cost of Social Distancing U.S. ~ $85B/Day PAT &Vaccines to Come Diagnostics 9/21 ~$51B/day GDP $18.8T Feel Sick 23©2020 Fred Brown
ImportancetotheWarEffort Ease of Social Distancing Low High Low High e.g., Farming/Ag New Residential Construction e.g., Retail Non-Essential Mfctg Restaurants Travel Industry Big venue events e.g., Research science vs Covid Infrastructure vs covid Strat call centers/consulting/exec Remote Workers IT professionals/Knowledge Workers e.g., Delivery Svs Police/Military Essential Mfctr/Infrastructure Cons. Infectious Disease Workers Teachers Virtualize Automate Robotics Manhattan Prjts Eliminate/Mothball Transfer/ Restructure (Immune market only) Activity Selection Matrix What to keep on and what to turn off Accelerate/ ExpectCompetitioin LimpAlong Expect New Entrants CAGR - 80% CAGR +100% CAGR +30% CAGR -20% Where are you today and where do you need to be? How do your personal behaviors change if you are at low vs high risk of contracting and dying from COVID? Surviving COVIDWAR Phase 1: Prioritizing Our SocioeconomicActivities Our only weapon vs COVID-19 today is social distancing How do we deploy it most effectively? 24©2020 Fred Brown
Cocktail Therapies Humans Counter-attack! Social Distancing & Diagnostics Drugs Vaccines Time Effectiveness 25©2020 Fred Brown
WHO SelectedTheir Antiviral Cocktail 3/20 CETI SelectedTheirTop 3 Vaccine Cock ail Treating Associated Illnesses140 Candidates in Development PAD BARDA HHS SelectedTheirTop 2 VaccineCock ail Diagnostics Needed! Reduces Fatalities, not COVID-19 1.Increases Risk of Failure 2.Reduces Scale 3.Threatens outcome consistency and comparability Red Flags Vaccine Manhattan Project Required NOW Attacking COVID-19 A new, difficult target Stem Cell Therapy 69 DruggableTargets Attacking theVirus Vaccines 26©2020 Fred Brown
COVID-19 Therapy Progression Likely Scenario Effectiveness Cure (R=0) Time2021 2022 2023 2024 Symptomologic &Co-Morbid DiseaseTreatments No Impact on COVID-19 R Significanty reduces mortality PassiveAnti-bodyTherapy (Convalescent Plasma) Small impact on C-19 R Boost for those at risk ExistingAnti-Virals,Anti-Bacterials + Anti-Inflamatories Small impact on C19 R Cocktail Component COVID 19 Specific Drugs Antiviral and Other Cocktail Components Stem Cells, other vaccine Insurance Policy Vaccines Partial Immunity Vaccine (2025) Today there are NO approved therapeutics to treat COVID 19 27©2020 Fred Brown
Cocktail Therapy: A Partial, Fragile Solution Treatments Therapeutics • Reduce disease progression and mortality • SymptomologicTreatment Antivirals • Pre-Exposure Prophylaxis • Post Exposure Prophylaxis • EarlyTreatment • LateTreatment Scenario A Outbreaks trigger conflicts over who receives treatment Unlimited population, usually sufficient supply Controlling COVID- before there s a complete vaccine available Defined populations, predictable demand Scenario B Scenario C Healthcare Workers Social distancing error (Day after pill) At Risk Populations Partial vaccines like Flu Tamiflu Cough suppressant, pain reliever Combinable cocktails: diagnostic/prognostic separators required Specific to co-morbid diseases, generally after onset IncreasingPersonalized/PrecisionMedicine Increasing Demand and Susceptibility to Outbreak Breakdowns Diagnostic/Prognostic Separators Required Diagnostic rqd 28©2020 Fred Brown
Cocktail Therapy: A Partial, Fragile Solution Treatments Therapeutics • Reduce disease progression and mortality • SymptomologicTreatment Antivirals • Pre-Exposure Prophylaxis • Post Exposure Prophylaxis • EarlyTreatment • LateTreatment Scenario A Outbreaks trigger conflicts over who receives treatment Unlimited population, usually sufficient supply Outbreaks can quickly destabilize the system. Defined populations, predictable demand Scenario B Scenario C Healthcare Workers Social distancing error (Day after pill) At Risk Populations Partial vaccines like Flu Tamiflu Cough suppressant, pain reliever Combinable cocktails: diagnostic/prognostic separators required Specific to co-morbid diseases, generally after onset IncreasingPersonalized/PrecisionMedicine Increasing Demand and Susceptibility to Outbreak Breakdowns RATIONING ISSUES Outbreaks Unpredictable Outbreak Demand Overwhelms Supply 29©2020 Fred Brown
Global Partnering & Synchronizing Issues • SupplyChains money, people and goods • Bridging Populations, Politics andTravel • Seasons • Compounding Natural Disasters • Policy Ripple Effects and Unintended Consequences • Frequency - COVID Global SupplyChain Manufacturing/Dist Real-Time Re-routing LongTerm/Risk Sharing Contracts More Flexible Plants, Eq.& x-training Global Multi-Sourcing Regulatory Flexibility Ne P od c De ign e g PPE S ab Reagen Demand Mgt Capacity Mgt MRP/ERP/QC Inventory Mgt Dist. Mgt Pedigree Mgt Health System D Forecast Models Usage Levels Inventory Levels Procurement/Blockchain RCM Distributor/Suppliers Labs Hosp Dr. Rx Predict/Sense/Respond Intelligence ©2020 Fred Brown 30
Rationing Societ s Winners and Losers in the War Free MarketTriage vs Central Planning • Who wins with one outbreak? With many? • Who wins early in life of the drug vs late? Rationing CocktailTherapy Effectiveness Low High Selective High ProcessControls e.g., StepTherapy Diagnostics Triage Free Market P i i i e b De i ed O c me B • What outcomes are most desirable? • Who decides? • How do they decide? • When do we start or stop rationing? • What rationing processes should be used? Country vs Country Sick vsWell Young vs Old Poor vs Rich T ibe T ibe Unequal Levels of Illness and Death Distrust among and between partners 31©2020 Fred Brown
We are Fighting a World War Unprecedented speed and scale will be required to win. Allied Global Command Regional Surgeon Generals Country Deployment Operational Excellence COVID Battle Infrastructure Innovation Strategy Health/Social System Responsiveness Battle Infrastructure Supply & Demand Mgt Diagnostic, Drug, Device, AI Strategy,Apps, Data Deployment Social Con ac ing Reg la o F ame o k Enfo cemen Citizen Perspective Financial Perspective Best Practices Aggregation and Monitoring Financial Management Social Economic Health Markets Money Local Commanders Cross-Border Management Fed & Fiscal Manage the SCIENCE Manage the EMOTION Our Forces vs . Implement a global hierarchy with a plan, balanced scorecard and metrics now. Marshall Plan Manhattan Project Medical/Social Policy & Best Practices 32©2020 Fred Brown
X Vaccines: The Silver Bullet – How Soon? Stable/Low MutationVirus Mutating/Multi-StrainVirus e.g., Influenza Constantly Mutating e.g., Malaria Single Dose + Booster High Low Seasonal Partial Trouble Effectiveness Mutagensis Silver Bullet Scenario Cocktail Scenario* War of Attrition Scenario Development Speed Slow Fast Scalability ProvenUnproven * Cocktail Scenario -The fastest route to some control may be PAT (Convalescent Plasma) Monoclonal antibody cocktails DNA 19mos13.4yrs 5 yrs If Safe and Efficacious, then… RNA Non-Replicating ViralVector Replicating ViralVector Live Attenuated Inactivated Protein Subunit No Scaled FastVaccines X Multiple Dose X Single Dose 33©2020 Fred Brown
Chloroquine (Malaria) Victory Paths - The Bets We Are Making Effectiveness Cure (R=0) Time 2021 2022 2023 2024 Co-Morbid/Symptom DiseaseTreatments COVID 19 Specific Drugs Antiviral and Other Cocktail Components Stem Cells, other vaccine Insurance Policy Vaccines Partial Immunity Vaccine (2025) 2020 2020- Magnified DATA Yes No Gilead Remdesivir (Ebola) Kaletra (HIV) Kaletra (HIV) + Interferon B BCG Convalescent Therapy Regeneron Monoclonal Cocktail Components Moderna CanSino Inovio CurVac Generex Shenzen (Repurposed PartialVaccine) Alnylam RNAi Jena Abcellera Takeda Harbour Vir BDB Emergent Sanofi Kevzara Roche Actemra Antibody Therapies Anti Virals Vaccines PassiveAnti-bodyTherapy (Convalescent Plasma) ExistingAnti-Virals,Anti-Bacterials + Anti-Inflamatories Start Ph 3ClinicalVaccine Trial? Moderna 25% Multiple attacks? Epidemiology? Economy, Societal? NovaVax 270 ClinicalTrials 140 DrugTreatment 78Vaccine Jan` April 5 SepJuly ©2020 Fred Brown 34 34©2020 Fred Brown
Innovation Challenges ▪ Reducing Infection Social & Behavioral Innovations Testing &Tracing/Immunity Management Repurposing Drugs ▪ Reducing Mortality More robust healthcare system Antivirals & vaccines Immune system response management & other therapeutic advances ▪ Creating Resilient Economy and Society Federal monetary and fiscal activity Efficient on/off switching Safe workplace protocols, increased use of virtualization,AI/ML, robotics, automation 35©2020 Fred Brown
Framework • Our time horizon must expand beyond what our imaginations are currently allowing us to imagine. • We are running a marathon, not a sprint • This enemy breaks all of our decision rules and comforts zones. Developing a predictive capability using current, unvarnished data and scenario pathways is required to win. The cold hard truth • This is far worse than the market crash of 2008, or 9/11.Those were events: this is an era. • Until we can vaccinate about 85% of the population, intermittent social distancing will be an economically and psychologically burdensome reality. • Business categories and populations will come back unevenly o Businesses who do not find a way to incorporate intermittent social distancing may never fully return o For the poor and disadvantaged populations, full economic recovery could easily take a decade or more. How we will win • Prepare for multiple scenarios and over-react when a response requirement is detected • Develop unprecedented and unpalatable management of individual behaviors that influence infection rate and deal with associated risks. • A great wave of innovation offers our chance of winning this war and returning to normalcy Conclusions 36©2020 Fred Brown
Implications: The New Normal ▪ It is still early days. Data is fragmentary, and coming in fast. New data can have an immediate and unpredictable impact on these recommendations stay tuned in. ▪ Human mobility, integration and globalization has brought many benefits and improvements to our lives. It also makes us more susceptible to pandemics ▪ This is our first, not our last pandemic ▪ We have to get good at pandemic response ▪ O effo no on be a a e of ime and ea e ▪ To win, we must build a global diagnostic testing, medicines development and economic response infrastructures, even under a silver bullet scenario ▪ This great wave of innovation will pay off for decades to come. ▪ Viral transmission and exponential growth are network effects. If you have heard any useful ideas in this presentation, be a super spreader tell all of your friends to tell their friends! 37©2020 Fred Brown
Appendix 38©2020 Fred Brown
Poor Good Poor Good DiseaseManagement Economic Policy Management Ger China Jpn US Emer Mkts It Fr UK Kor Twn Ir Sng Sp EU Region ASEAN Circle Size = GDP Short Term – Economy is Driven by COVID Management Capabilities and Outcomes 39©2020 Fred Brown
Economic Implications • Countries that do not act quickly with unprecedented neutralizing stimulus to counteract the social distancing economic impact will suffer permanent economic damage. • Economic forecasts and policy models that are not directly driven by COVID 19 Epidemiologic models will be off by an order of magnitude (Exponential Growth vs Linear Response) Regional • The US will be under tremendous pressure to restore economic order. It will be unable to until COVID-19 is under better control. ( My model runs 3/24/20 projects August 1 unemployment 27%, Real Unemp 42%, 2020 4,5,6/20 GDP -62%) • Compared to other OECD countries, the US must do more just to stand still to prevent demand disruption. Immediate stimulus package throughAugust should be ~2.5x what is planned now. Speed is critical. • EU will suffer high mortality due to elderly populations. • China will delay stimulus for cosmetic reasons until Fall. It is better positioned to establish a new regional order. • Emerging and second world countries will lose the most at least ten years of development and millions of deaths. Global • Significant investment is needed to create an infrastructure to control pandemics. This will slow economic stimulus. • Country and regional supply chain strengthening will be required to diversify global risk and manage outbreaks. • A policy framework like BrettonWoods must be established upon the subsidence of the virus to recover the global demand function and restore confidence. Without it, a permanent deflation of asset values is likely globally. 40©2020 Fred Brown
Innovation Challenges ▪ Reducing Infection Social & behavioral innovations Testing &Tracing Antivirals &Vaccines ▪ Reducing Mortality More robust healthcare system Antivirals Immune system response management & other therapeutic advances ▪ Creating Resilient Economy and Society Federal monetary and fiscal activity Efficient on/off switching Safe workplace protocols, increased use of virtualization,AI/ML, robotics, etc. 41©2020 Fred Brown
Welcome to The Marathon ▪ I believe this is our best option. It works like this: 1. Use strong social distancing to greatly lower infection rate 2. Establish program of comprehensive individual monitoring for infection, risk factors for infection, and immunity 3. Selectively ease restrictions to allow economic activity to resume 4. Use individual data to constrain individual activity 5. Monitor gating indicators: for example, ICU bed use 6. When the indicators reveal that infection rates are beginning to rise, restore strong social distancing quickly to keep the infection spike as small and brief as possible 7. Adapt to changing circumstances: increased healthcare system capacity and efficacy in preventing death, availability of antiviral cocktails, better data on efficacy of behavioral constraints, rising immunity level in general population, availability of vaccine, competence at switching economy off and on 42©2020 Fred Brown
For questions and comments fred.brown.covid@gmail.com April 5, 2020 43©2020 Fred Brown

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Defeating COVID-19

  • 1.
  • 2.
    Where I veBeen ▪ M life o k i defea ing illne and i al e idemic ▪ My epidemic intervention experience includes: Developing and commercializing first test for HIV (Centocor) Developing and commercializing polyvalent vaccines (GSK, Novartis, (many)) Managing Roche Diagnostic andTamiflu suppression of H5N1 Influenza ▪ I have also led 0r supported the discovery, development and/or launch of 27 pharmaceutical, 13 diagnostic and 6 vaccine products saving 5.6M lives per year and achieving combined peak sales of over $35B Global Head, Hoffmann LaRoche Product Lifecycle, Partnerships and Informatics. Co-founder and executive leader of two innovative Life Science companies like Alkermes (NASDAQ: ALKS). ▪ Board Member of Continuing Medical Education - Johns Hopkins Medical School/ES4P 2©2020 Fred Brown
  • 3.
    Where I mComing From ▪ I believe humans are responding too slowly and too narrowly to the scale and speed of the pandemic threat ▪ These are solely my opinions based on my experience and the data available on 4/5/20 These are early days and facts are scarce; beware of certainty (economists, scientists, politicians, pundits, investment advisors, relatives) Government and industry leaders are naturally biased on behalf of their institutions; evaluate their statements accordingly My only interest here is to save lives ▪ I ee m elf a an an igen ing o im la e he o ld imm ne system to respond more robustly to the threat 3©2020 Fred Brown
  • 4.
    Goals of ThisPresentation ▪ To help people think clearly about the huge issues raised by the COVID-19 pandemic You as leaders have the potential to make a real difference; I want you to know the facts and use them: feel free to steal and use this material! Other audiences: scientists, elected officials, journalists, general public ▪ To make it easier to parse the daily flood of information and opinion on the topic ▪ To provide some easy frameworks with signals and indicators to help people determine where we are in this war 4©2020 Fred Brown
  • 5.
    What We reUp Against ▪ SARS CoV-2 is an exceptionally dangerous virus We have no immunity: it will take a long time to reach herd effect I highl con agio i co ld infec mo of he o ld a idl I a kille le ing i n i co e o ld be ca a o hic I in a famil of i e fo hich accine a e diffic l o de elo I abili o m a e o e ade accine and an i i al i nkno n ▪ Our world is tailor-made to be vulnerable Our economies depend on global supply chains, pervasive travel, face-to-face service industries, and high population densities in concentrated urban areas We e mo e mobile and mo e ocial han h man ha e e e been befo e Our information environment is ubiquitous, engaging, and unreliable Our politics are polarized 5©2020 Fred Brown
  • 6.
    Where We Stand ▪Since first identified in humans in China in late 2019, COVID-19 has appeared in 184 countries, accounted for 100,000 confirmed deaths, and overwhelmed healthcare systems in China, Italy, Spain, and the US ▪ Hence e e managing a a o la ion le el no an indi id al le el ▪ The only response thus far which has moderated the exponential growth of infections has been strong social distancing, including extreme reductions in travel ▪ Such social distancing brings economies to a near-standstill ▪ The virus itself is impairing our ability to respond because it disrupts our fragile just-in-time systems and global supply chains.This impacts healthcare, pharmaceuticals, medical supplies, and medical equipment 6©2020 Fred Brown
  • 7.
    #ofInfected 1 5 30 15R = 1.25 Influenza Every Day Counts Influenza has a typical infection rate of 1.25. In 30 days from the fi ca e o ll ha e ca e if o don intervene. Days 7©2020 Fred Brown
  • 8.
    #ofInfected Days 1 530 15 R = 1.25 Influenza Every Day Counts 406 R = 2.5 COVID 19 COVID-19 has a typical infection rate of 2.5. In 30 days from the first ca e o ll ha e ca e if o don intervene. Influenza has a typical infection rate of 1.25. In 30 days from the fi ca e o ll ha e ca e if o don intervene. 8©2020 Fred Brown
  • 9.
    #ofInfected Days 1 530 15 R = 1.25 Influenza 406 China intervened on Day 12. Had they intervened just SEVEN DAYS EARLIER, they would have cut their 30-day case count in half. Had they waited SEVEN DAYS LATER, they would have let their case count increase nine-fold. The virus attack is exponential. Our responses are linear. Every Day Counts x/2 9x R = 2.5 COVID 19 9©2020 Fred Brown
  • 10.
    #ofInfected Days 1 530 15 R = 1.25 Influenza 406 Every Day Counts Take-Aways 1. It s better to over-respond to an epidemic early and back off rather than to hope, wait and see it will overwhelm you • COVID-19 reproduces exponentially while our responses are linear • Our traditional processes will not work to control COVID-19 2. Data, Data, Data • Real time, not batch • Granular, broad, and searchable, not siloed 3. Range of uncertainty also increases exponentially over time with no new data R = 2.5 COVID 19 x/2 9x 10©2020 Fred Brown
  • 11.
    How Should WeProceed? ▪ Sufficiently strong social distancing collapses infection rates but devastates economies & societies.Three restoration strategies have been suggested: 1. Get lucky. Perhaps one of the first vaccines to be tested will prove safe, effective, and scalable.With a lot of luck, we could arrive at a post-COVID-19 era as soon as late 2021. 2. Get brutal. If allowed to run rampant, this virus might follow the path of the 1918 Influenza epidemic, which eventually died off after killing perhaps hundreds of millions in three trips around the world. It left most of the survivors with immunity, insuring its own demise. 3. Win a marathon. Learn to manage social behavior to minimize risk while restoring some economic activity. Press ahead on antivirals and vaccines with realistic expectations. Innovate to optimize economic benefit under duress. This could last for years. 11©2020 Fred Brown
  • 12.
    Getting Lucky: HowLucky Can We Get? ▪ Vaccines against viruses average 13 years to develop ▪ So far, no vaccines exist for any human Coronaviruses ▪ Today there are 78 COVID vaccine candidates under investigation ▪ There is no consensus yet about most likely candidates, an indication of early days ▪ Huge resources have been committed. There is initial coordination between some efforts, but the vast majority remain independent. Regulatory agencies have promised streamlined processes ▪ Odds of getting lucky? Less than 20% ▪ We need a Plan B 12©2020 Fred Brown The costs of a decision could be orders of magnitude higher medically, economically, psychologically and socially if unchecked. Social distance shut-downs have projectable economic and health costs. Unchecked pandemics do not.
  • 13.
    Getting Brutal: Bettingon Herd Immunity Bet: Total humanitarian costs of shutting down the economy > Total costs of letting coronavirus run its course We are early in this war to make an all-or-nothing decision. We know so little about COVID and are defenseless against it. Leaders have always bought time until they know more about alternatives and true risks of deploying such a strategy. 1. Wild Bet right now we have no idea of the true, eventual downside risk ▪ COVID e fa ali e od c i e and m a ion a e ▪ The range of medical issues it can cause across diverse genetic populations and broader ranges of underlying conditions, ▪ The degree and duration of herd immunity after infection, and ▪ The costs of a decision could be orders of magnitude higher medically, economically, psychologically and socially if unchecked. Social distance shut-downs have projectable economic and health costs. Unchecked pandemics do not. ▪ Until a detection and public health infrastructure is in place to guide deploying a brutal strategy, it could run tragically amok. 2. This bet is all in ▪ A deployment decision is non-reversible and on a hair-trigger. We have no weapons to fight COVID 19 today- unchecked, it co ld infec mo of he o ld o la ion in a ea o o ▪ Healthcare services would be utterly overwhelmed ▪ Total COVID19-related mortality rates worldwide are uncertain, but global deaths on the order of 1 2% of total population 75 to 150 million people in 2021-22 would be a plausible first guess. ▪ Any large mobile population can trigger a brutal pathway that envelops the world. Once initiated, we have no infrastructure to detect or halt the virus. It would run its course unchecked - No do-overs. Nowhere to hide. ▪ This choice is morally, psychologically, and politically devastating ©2020 Fred Brown 13
  • 14.
    Welcome to theMarathon: COVID-19 War Games Four Scenarios: 1. Spontaneous Combustion (<1% chance) The virus mysteriously sputters out. It has happened before. 2. Magic Bullet (<20% chance) We get lucky fast with an effective vaccine ~19 months (<20% chance) 3. Therapeutic Cocktails (60% chance) Intermittent social distancing, testing and tracing; and a sequence of improving cocktails and partial vaccines; then an effective vaccine in ~5 years (60% chance) 4. War of Attrition (20% chance) Similar to #3, but on a more typical timeline for development of vaccines, antivirals, and other treatments, leading to an effective vaccine in ~10 years (20% chance) 14©2020 Fred Brown
  • 15.
    Welcome to theMarathon: COVID-19 War Games 2020 2021 2022 2026 2027 2028 2029 2030202520242023 Economic & Social Normalcy 95 100% 30-60% 60 75% 75-95% LEGEND Magic Bullet: revolutionary vaccine by Q2 2021, perfect execution, no COVID-19 bounce-back Spontaneous Combustion: COVID-19 quickly sputters out<1% <20% 20% 60% Convalescent Plasma Repurposed Drugs Therapeutics Antivirals PartialVaccine Vaccine Therapeutic Cocktails: behavior management and drug treatments reduce harm and buy time until an effective vaccine takes over War of Attrition: traditional drug and vaccine timelines and failures. COVID-19 may fight back with mutationsConvalescent Plasma Repurposed Drugs Therapeutics Antivirals PartialVaccine Vaccine Vaccine 15©2020 Fred Brown
  • 16.
    Winning a Marathon(Full of Sprints) Social Distancing & Diagnostics Drugs Vaccines Time Effectiveness Herd Immunity 16©2020 Fred Brown
  • 17.
    Phase Shifts ▪ PhaseI Social Distancing & Diagnostics: non-pharmaceutical; requires intermittent strict behavioral constraints: test & trace, social distancing, and mo e AKA bo ing ▪ A third of the economy in any one geography will be turned off at any one time. Unsynchronizable.Governed by adaptive triggering ▪ Phase II Drugs: useful anti-viral cocktail(s) become available to reduce severity, frequency, and mortality of infections which reduces duration and frequency of boxing episodes ▪ Phase III Vaccines: effective vaccine(s) become available at scale (if virus cooperates); vaccines accelerate herd immunity, boxing ends ▪ Within phases, incremental improvements; at phase shifts, bigger jumps 17©2020 Fred Brown
  • 18.
    NewConfirmedCases Non OutbreakArea Shutdown2 Months OutbreakArea Shutdown (Wuhan) 2.5 Months FY GDP 6.1+% FY GDP 3.3-% The First COVID-19 Attack (China): One & Done? 4000 3500 3000 2500 2000 1500 1000 500 0 18©2020 Fred Brown
  • 19.
    Or Recurring Attacks Sep 21 Nov 21 Jul 21 May 21 Mar 21 Jul 20 May 20 Jan 21 Nov 20 Sep 20 Mar 20 Trigger: >2.5%of Available ICU Beds Devoted to COVID-19 Boxes = Economy off d e o social distancing and other restrictions Wi ho he a e ic and accine o figh back h man m o imi e ocial di ancing i h ada i e igge ing Herd Immunity? After wave 1, 95% of us remain susceptible. Herd immunity may require 55-85% to have antibodies and may only last for one season. Goal: Make the boxes narrower and farther apart, to keep the economy switched on more of the time. 19©2020 Fred Brown
  • 20.
    D Sense and Respond 4weeks ago 3 weeks ago 2 weeks ago 1 weeks ago Today In 1 week In 2 weeks Exposure Symptoms Resolution 1 Death Infectious 14 days - Number Infected 100 200 400 800 1600 3200 6400 2 Deaths 4 Deaths Clinical Surrogate (Death)TriggerDiagnostic TestTriggers Case Fatality Rate 1% Doubling Time 1Week Shorten the Detection Window VS. • Humans - No counter attack technologies COVID A mame • Long infectious period • Large asymptomatic population • Moderate death rate • Mutation rate stable so far 20©2020 Fred Brown
  • 21.
    The Dance ofScience and Economics ManageThe Box to Increase Normalcy 1. Narrow the length of economy off by increasing the compliance to distancing measures 2. Reduce the frequency of economy off with improved drugs and diagnostics/tracing control 3. Raise the height of the trigger (adaptively) with improved health system capacity Increase Compliance • Infrastructure • Diagnostics • AI . . . . . . Step 2 Medicines • Therapeutics • Anti-virals • PartialVaccines Economy Off . . . Step 1 Reduce Shut-Down Duration Reduce Shut-Down Frequency 21 21©2020 Fred Brown
  • 22.
    Our Phase 1Weapons 1. Diagnose Surveillance All Crowded Events/Venues Minimum - 128 M tests per week 85% Predictive, Instant, <1c $2.00 PCR/Point-of-Care Accurate ActiveVirus Detection - Minimum capacity 75M tests per week 0.04% False neg. rate, 15 min, $20 -$50 Monitor Antibody Detection Minimum capacity 65M per week 0.01 % False pos. rate, 2 d, $15 - $50 COVID WAZE COVID Expert Bot Contact Tracing &Status National COVID- Registry Global Vaccines Registry 2.Track &Trace • Artifical Intelligence • Expert Systems • Machine Learning • Predictive Analytics Apps 3. Auto-Mitigate Large infrastructure upgrades are required immediately in three areas to support and automate our social distance defenses ©2020 Fred Brown 22©2020 Fred Brown
  • 23.
    Manhattan Project Identify,Isolate and Auto-Trace Q2/2020 – Building the New Infrastructure Q3/2021 - Precision Monitoring or Self/Dr. Report Surveillance ContactTracking TEST No COVID 30% 70% Hospital Field Hospital Home (+/- Smart) Quarantine /Isolation COVID Confirmed Triage ClinicVery ill ill Population Sick Asymptomatic Immune Well Low Risk Well High Risk Anti-body Testing For Immunity Vaccine Registry Tracking App - Immune Cert - Test Checks - Location - Result - GPS - O he 43% Telehealth COVID Suspected 5/20 - Cost of Social Distancing U.S. ~ $85B/Day PAT &Vaccines to Come Diagnostics 9/21 ~$51B/day GDP $18.8T Feel Sick 23©2020 Fred Brown
  • 24.
    ImportancetotheWarEffort Ease of SocialDistancing Low High Low High e.g., Farming/Ag New Residential Construction e.g., Retail Non-Essential Mfctg Restaurants Travel Industry Big venue events e.g., Research science vs Covid Infrastructure vs covid Strat call centers/consulting/exec Remote Workers IT professionals/Knowledge Workers e.g., Delivery Svs Police/Military Essential Mfctr/Infrastructure Cons. Infectious Disease Workers Teachers Virtualize Automate Robotics Manhattan Prjts Eliminate/Mothball Transfer/ Restructure (Immune market only) Activity Selection Matrix What to keep on and what to turn off Accelerate/ ExpectCompetitioin LimpAlong Expect New Entrants CAGR - 80% CAGR +100% CAGR +30% CAGR -20% Where are you today and where do you need to be? How do your personal behaviors change if you are at low vs high risk of contracting and dying from COVID? Surviving COVIDWAR Phase 1: Prioritizing Our SocioeconomicActivities Our only weapon vs COVID-19 today is social distancing How do we deploy it most effectively? 24©2020 Fred Brown
  • 25.
    Cocktail Therapies HumansCounter-attack! Social Distancing & Diagnostics Drugs Vaccines Time Effectiveness 25©2020 Fred Brown
  • 26.
    WHO SelectedTheir Antiviral Cocktail 3/20 CETI SelectedTheirTop3 Vaccine Cock ail Treating Associated Illnesses140 Candidates in Development PAD BARDA HHS SelectedTheirTop 2 VaccineCock ail Diagnostics Needed! Reduces Fatalities, not COVID-19 1.Increases Risk of Failure 2.Reduces Scale 3.Threatens outcome consistency and comparability Red Flags Vaccine Manhattan Project Required NOW Attacking COVID-19 A new, difficult target Stem Cell Therapy 69 DruggableTargets Attacking theVirus Vaccines 26©2020 Fred Brown
  • 27.
    COVID-19 Therapy ProgressionLikely Scenario Effectiveness Cure (R=0) Time2021 2022 2023 2024 Symptomologic &Co-Morbid DiseaseTreatments No Impact on COVID-19 R Significanty reduces mortality PassiveAnti-bodyTherapy (Convalescent Plasma) Small impact on C-19 R Boost for those at risk ExistingAnti-Virals,Anti-Bacterials + Anti-Inflamatories Small impact on C19 R Cocktail Component COVID 19 Specific Drugs Antiviral and Other Cocktail Components Stem Cells, other vaccine Insurance Policy Vaccines Partial Immunity Vaccine (2025) Today there are NO approved therapeutics to treat COVID 19 27©2020 Fred Brown
  • 28.
    Cocktail Therapy: APartial, Fragile Solution Treatments Therapeutics • Reduce disease progression and mortality • SymptomologicTreatment Antivirals • Pre-Exposure Prophylaxis • Post Exposure Prophylaxis • EarlyTreatment • LateTreatment Scenario A Outbreaks trigger conflicts over who receives treatment Unlimited population, usually sufficient supply Controlling COVID- before there s a complete vaccine available Defined populations, predictable demand Scenario B Scenario C Healthcare Workers Social distancing error (Day after pill) At Risk Populations Partial vaccines like Flu Tamiflu Cough suppressant, pain reliever Combinable cocktails: diagnostic/prognostic separators required Specific to co-morbid diseases, generally after onset IncreasingPersonalized/PrecisionMedicine Increasing Demand and Susceptibility to Outbreak Breakdowns Diagnostic/Prognostic Separators Required Diagnostic rqd 28©2020 Fred Brown
  • 29.
    Cocktail Therapy: APartial, Fragile Solution Treatments Therapeutics • Reduce disease progression and mortality • SymptomologicTreatment Antivirals • Pre-Exposure Prophylaxis • Post Exposure Prophylaxis • EarlyTreatment • LateTreatment Scenario A Outbreaks trigger conflicts over who receives treatment Unlimited population, usually sufficient supply Outbreaks can quickly destabilize the system. Defined populations, predictable demand Scenario B Scenario C Healthcare Workers Social distancing error (Day after pill) At Risk Populations Partial vaccines like Flu Tamiflu Cough suppressant, pain reliever Combinable cocktails: diagnostic/prognostic separators required Specific to co-morbid diseases, generally after onset IncreasingPersonalized/PrecisionMedicine Increasing Demand and Susceptibility to Outbreak Breakdowns RATIONING ISSUES Outbreaks Unpredictable Outbreak Demand Overwhelms Supply 29©2020 Fred Brown
  • 30.
    Global Partnering &Synchronizing Issues • SupplyChains money, people and goods • Bridging Populations, Politics andTravel • Seasons • Compounding Natural Disasters • Policy Ripple Effects and Unintended Consequences • Frequency - COVID Global SupplyChain Manufacturing/Dist Real-Time Re-routing LongTerm/Risk Sharing Contracts More Flexible Plants, Eq.& x-training Global Multi-Sourcing Regulatory Flexibility Ne P od c De ign e g PPE S ab Reagen Demand Mgt Capacity Mgt MRP/ERP/QC Inventory Mgt Dist. Mgt Pedigree Mgt Health System D Forecast Models Usage Levels Inventory Levels Procurement/Blockchain RCM Distributor/Suppliers Labs Hosp Dr. Rx Predict/Sense/Respond Intelligence ©2020 Fred Brown 30
  • 31.
    Rationing Societ sWinners and Losers in the War Free MarketTriage vs Central Planning • Who wins with one outbreak? With many? • Who wins early in life of the drug vs late? Rationing CocktailTherapy Effectiveness Low High Selective High ProcessControls e.g., StepTherapy Diagnostics Triage Free Market P i i i e b De i ed O c me B • What outcomes are most desirable? • Who decides? • How do they decide? • When do we start or stop rationing? • What rationing processes should be used? Country vs Country Sick vsWell Young vs Old Poor vs Rich T ibe T ibe Unequal Levels of Illness and Death Distrust among and between partners 31©2020 Fred Brown
  • 32.
    We are Fightinga World War Unprecedented speed and scale will be required to win. Allied Global Command Regional Surgeon Generals Country Deployment Operational Excellence COVID Battle Infrastructure Innovation Strategy Health/Social System Responsiveness Battle Infrastructure Supply & Demand Mgt Diagnostic, Drug, Device, AI Strategy,Apps, Data Deployment Social Con ac ing Reg la o F ame o k Enfo cemen Citizen Perspective Financial Perspective Best Practices Aggregation and Monitoring Financial Management Social Economic Health Markets Money Local Commanders Cross-Border Management Fed & Fiscal Manage the SCIENCE Manage the EMOTION Our Forces vs . Implement a global hierarchy with a plan, balanced scorecard and metrics now. Marshall Plan Manhattan Project Medical/Social Policy & Best Practices 32©2020 Fred Brown
  • 33.
    X Vaccines: The SilverBullet – How Soon? Stable/Low MutationVirus Mutating/Multi-StrainVirus e.g., Influenza Constantly Mutating e.g., Malaria Single Dose + Booster High Low Seasonal Partial Trouble Effectiveness Mutagensis Silver Bullet Scenario Cocktail Scenario* War of Attrition Scenario Development Speed Slow Fast Scalability ProvenUnproven * Cocktail Scenario -The fastest route to some control may be PAT (Convalescent Plasma) Monoclonal antibody cocktails DNA 19mos13.4yrs 5 yrs If Safe and Efficacious, then… RNA Non-Replicating ViralVector Replicating ViralVector Live Attenuated Inactivated Protein Subunit No Scaled FastVaccines X Multiple Dose X Single Dose 33©2020 Fred Brown
  • 34.
    Chloroquine (Malaria) Victory Paths -The Bets We Are Making Effectiveness Cure (R=0) Time 2021 2022 2023 2024 Co-Morbid/Symptom DiseaseTreatments COVID 19 Specific Drugs Antiviral and Other Cocktail Components Stem Cells, other vaccine Insurance Policy Vaccines Partial Immunity Vaccine (2025) 2020 2020- Magnified DATA Yes No Gilead Remdesivir (Ebola) Kaletra (HIV) Kaletra (HIV) + Interferon B BCG Convalescent Therapy Regeneron Monoclonal Cocktail Components Moderna CanSino Inovio CurVac Generex Shenzen (Repurposed PartialVaccine) Alnylam RNAi Jena Abcellera Takeda Harbour Vir BDB Emergent Sanofi Kevzara Roche Actemra Antibody Therapies Anti Virals Vaccines PassiveAnti-bodyTherapy (Convalescent Plasma) ExistingAnti-Virals,Anti-Bacterials + Anti-Inflamatories Start Ph 3ClinicalVaccine Trial? Moderna 25% Multiple attacks? Epidemiology? Economy, Societal? NovaVax 270 ClinicalTrials 140 DrugTreatment 78Vaccine Jan` April 5 SepJuly ©2020 Fred Brown 34 34©2020 Fred Brown
  • 35.
    Innovation Challenges ▪ ReducingInfection Social & Behavioral Innovations Testing &Tracing/Immunity Management Repurposing Drugs ▪ Reducing Mortality More robust healthcare system Antivirals & vaccines Immune system response management & other therapeutic advances ▪ Creating Resilient Economy and Society Federal monetary and fiscal activity Efficient on/off switching Safe workplace protocols, increased use of virtualization,AI/ML, robotics, automation 35©2020 Fred Brown
  • 36.
    Framework • Our timehorizon must expand beyond what our imaginations are currently allowing us to imagine. • We are running a marathon, not a sprint • This enemy breaks all of our decision rules and comforts zones. Developing a predictive capability using current, unvarnished data and scenario pathways is required to win. The cold hard truth • This is far worse than the market crash of 2008, or 9/11.Those were events: this is an era. • Until we can vaccinate about 85% of the population, intermittent social distancing will be an economically and psychologically burdensome reality. • Business categories and populations will come back unevenly o Businesses who do not find a way to incorporate intermittent social distancing may never fully return o For the poor and disadvantaged populations, full economic recovery could easily take a decade or more. How we will win • Prepare for multiple scenarios and over-react when a response requirement is detected • Develop unprecedented and unpalatable management of individual behaviors that influence infection rate and deal with associated risks. • A great wave of innovation offers our chance of winning this war and returning to normalcy Conclusions 36©2020 Fred Brown
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    Implications: The NewNormal ▪ It is still early days. Data is fragmentary, and coming in fast. New data can have an immediate and unpredictable impact on these recommendations stay tuned in. ▪ Human mobility, integration and globalization has brought many benefits and improvements to our lives. It also makes us more susceptible to pandemics ▪ This is our first, not our last pandemic ▪ We have to get good at pandemic response ▪ O effo no on be a a e of ime and ea e ▪ To win, we must build a global diagnostic testing, medicines development and economic response infrastructures, even under a silver bullet scenario ▪ This great wave of innovation will pay off for decades to come. ▪ Viral transmission and exponential growth are network effects. If you have heard any useful ideas in this presentation, be a super spreader tell all of your friends to tell their friends! 37©2020 Fred Brown
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  • 39.
    Poor Good Poor Good DiseaseManagement Economic PolicyManagement Ger China Jpn US Emer Mkts It Fr UK Kor Twn Ir Sng Sp EU Region ASEAN Circle Size = GDP Short Term – Economy is Driven by COVID Management Capabilities and Outcomes 39©2020 Fred Brown
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    Economic Implications • Countriesthat do not act quickly with unprecedented neutralizing stimulus to counteract the social distancing economic impact will suffer permanent economic damage. • Economic forecasts and policy models that are not directly driven by COVID 19 Epidemiologic models will be off by an order of magnitude (Exponential Growth vs Linear Response) Regional • The US will be under tremendous pressure to restore economic order. It will be unable to until COVID-19 is under better control. ( My model runs 3/24/20 projects August 1 unemployment 27%, Real Unemp 42%, 2020 4,5,6/20 GDP -62%) • Compared to other OECD countries, the US must do more just to stand still to prevent demand disruption. Immediate stimulus package throughAugust should be ~2.5x what is planned now. Speed is critical. • EU will suffer high mortality due to elderly populations. • China will delay stimulus for cosmetic reasons until Fall. It is better positioned to establish a new regional order. • Emerging and second world countries will lose the most at least ten years of development and millions of deaths. Global • Significant investment is needed to create an infrastructure to control pandemics. This will slow economic stimulus. • Country and regional supply chain strengthening will be required to diversify global risk and manage outbreaks. • A policy framework like BrettonWoods must be established upon the subsidence of the virus to recover the global demand function and restore confidence. Without it, a permanent deflation of asset values is likely globally. 40©2020 Fred Brown
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    Innovation Challenges ▪ ReducingInfection Social & behavioral innovations Testing &Tracing Antivirals &Vaccines ▪ Reducing Mortality More robust healthcare system Antivirals Immune system response management & other therapeutic advances ▪ Creating Resilient Economy and Society Federal monetary and fiscal activity Efficient on/off switching Safe workplace protocols, increased use of virtualization,AI/ML, robotics, etc. 41©2020 Fred Brown
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    Welcome to TheMarathon ▪ I believe this is our best option. It works like this: 1. Use strong social distancing to greatly lower infection rate 2. Establish program of comprehensive individual monitoring for infection, risk factors for infection, and immunity 3. Selectively ease restrictions to allow economic activity to resume 4. Use individual data to constrain individual activity 5. Monitor gating indicators: for example, ICU bed use 6. When the indicators reveal that infection rates are beginning to rise, restore strong social distancing quickly to keep the infection spike as small and brief as possible 7. Adapt to changing circumstances: increased healthcare system capacity and efficacy in preventing death, availability of antiviral cocktails, better data on efficacy of behavioral constraints, rising immunity level in general population, availability of vaccine, competence at switching economy off and on 42©2020 Fred Brown
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    For questions andcomments fred.brown.covid@gmail.com April 5, 2020 43©2020 Fred Brown