Why CHDI reached out to C-Path

Robi BlumensteinPresident, CHDI Management, Inc.robi.blumenstein@chdifoundation.org

Silver Spring, MDNovember 6, 2017

- or -

How learning to play chess can inform efforts to bring effective

treatments for HD to patients

Acknowledgments

Vahri BeaumontJonathan Bard

Doug MacdonaldLadislav Mrzljak

Larry ParkRoger CachopeDavid Howland

Seung KwakRobert Pacifici

Celia DominguezLeticia Toledo-Sherman

John WityakMichel MaillardBeth BorowskyAndrew Wood

Valentina DildaCheryl Fitzer-AttasCristina Sampaio

Andrea VarroneChrister HalldinJenny Häggkvist

P. Fazio

Steve ZhangPhilip GregoryEd RebarFyodor Ursinov

Nikisha CartyYalda SedaghatKarsten TillackAndreas WeissMichael PrimeFrank HerrmannSabine SchaertlChristopher BrownDaniel Clark-FrewSamuel CoePaul GilesSamantha GreenSarah HayesDuane HigginsRichard MarstonMatthew MillsAnthony PadfieldMadlen HotzeKathrin PetersenManuela HeßmannGlauco TarozzoStefanie JahnMiriam BaritschTom SchwagarusNicole Höschen,Marta KotasinskaKarsten KottigGalina BursowChristina ThiedeLisa Mettler

Sarah TabriziEd Wild

Blair Leavitt

Frank BennetHolly Kordasiewicz

Laura OrsattiRoberto SpezialeAlessandra CeccacciChantal PaoliniLicia TomeiAlberto Bresciani

Czech Institute of Animal Physiology Zdenka EllederovaJan Motlik

University of AucklandSusanne ReidRussell Snell

Aeash RassoulpourMariette Heins

David FischerMichela Tessari

George McAllister

Acknowledgements

Science AdminRobertPacifici RuthBasuCristinaSampaio DavidRankinCeliaDominguez EileenNeacyIgnacioMunoz-SanjuanThomasVogtAndrewWood

ControlPreManifestHD

A last word on strategy… and hope

PreManifestControl HD

CONFIDENTIAL INFORMATION11

CAG age Model, 80% power, alpha = .05, 5% annual censoring

10% 20% 30% 40% 50%3 19,509 4,690 1,997 1,071 649 4 13,669 3,297 1,409 759 462 5 10,321 2,496 1,070 578 353 6 8,196 1,986 853 462 283

Estimates for a group that is all gene-expanded, with CAG lengths known

Magnitude of Therapeutic Effect

Year

sfo

llow

ed

circa 2004

Phenotype progression through States 1 - 9

Distance between states proportional to empirical durations in years

1 2 3 4 5 6 7 8 9

Motor, cognition & GCI

Motor, cognition, GCI+ occupation

Cognition, motor + moderate activities (walking, climbing)

Function, SF & Caregiver survey

Motor, cognition + MMSE

Cognition, motor& function

Function, cognition,motor, physio & MMSE

abc: new outcome measures

10#$

10%#$

A word on strategy… and hope

Number of half moves played

Expe

cted

hal

f mov

es re

mai

ning

CONFIDENTIAL INFORMATION20