anaconda-powered rapid drug discovery | anacondacon 2017

© 2017 Recursion Pharmaceuticals

DISRUPTING DRUG DISCOVERYWITH THE POWER OF IMAGES

Blake Borgeson Co-Founder & CTO [email protected]

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PROBLEMSLOW PACE OF DRUG DISCOVERY

Maren. 38 months old. Her parents sent us this photo.

Thousands of rare genetic diseases exist, nearly all untreated.

Millions of people in the US alone are affected.

The traditional drug discovery model of one disease, one pathway would take hundreds of years to address them all.

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Monogenic diseases often present with specific structural phenotypes, as with the distinct facial

features of patients with Cornelia de Lange Syndrome. Similarly, specific structural signatures

for many monogenic diseases are accessible via cellular images.

Healthy child

Child with rare genetic disease

(Cornelia de Lange Syndrome)

Healthy cells

Genetic disease model cells

(Cornelia de Lange Syndrome)


SOLUTIONTHE POWER OF IMAGES

\© 2017 Recursion Pharmaceuticals

TECHNOLOGYAUTOMATED & SCALABLE

Healthy Disease Disease + Drug?

Cell Painting images of cellular models of human diseases reveal hundreds of structural and

functional features unique to each disease model. These features encode disease specific

phenotypic profiles that can be extracted using computer vision methods.

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Indi

vidu

al F

eatu

res

0 IncreaseDecrease

Nuclear TextureNuclear RadiusER IntensityRNA IntensityMitochondrial Texture


HTS biological tools enable us to build hundreds of disease models ‘per plate’

Computer vision and machine learning enable the efficient extraction and meaningful representation of the data

We use the latest biological tools to build hundreds of unique genetic disease models, imaging tens

of thousands of cells per model, and extracting nearly 1,000 structural features from every cell.

With a disease-specific cellular phenotype in hand, we can ask whether any drug rescues the

defects back to ‘health.’ This approach represents a scalable and generalizable drug

discovery assay.

TECHNOLOGYAUTOMATED & SCALABLE


DEVELOPMENTCASE STUDY: CEREBRAL CAVERNOUS MALFORMATION

Weakening of vessel walls

100,000+ symptomatic patients in U.S.

Stroke, headache, epilepsy

Adult-onset, progressive

No medical treatment

Patient Brain MRI



Weakening of vessel walls

100,000+ symptomatic patients in U.S.

Stroke, headache, epilepsy

Adult-onset, progressive

No medical treatment

Patient Brain MRI

Tested 2,000 compounds Selected 2

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Mouse brains showing lesions (healthy brains have none)

Mouse disease model

Tempol

Vitamin D

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Rec001 and Rec002 Reduce Lesion Burden in CCM

Mice

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Gibson, et al., Circulation. In Press

Standard Diet REC001 Diet REC002 Diet

REC002 Diet

REC001 Diet

Standard Diet

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www.RecursionPharma.com

Rec001 and Rec002 Reduce Lesion Burden in CCM Mice




REC002 Diet

REC001 Diet

Standard Diet

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REC002 Diet

REC001 Diet

Standard Diet

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REC002 Diet

REC001 Diet

Standard Diet

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Mouse brains showing lesions (healthy brains have none)

Mouse disease model

Tempol

Vitamin D

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w.RecursionPharm

a.com

Rec001 and Rec002 Reduce Lesion Burden in CCM

Mice

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w.RecursionPharm

a.com



REC002 Diet

REC001 Diet

Standard Diet

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REC002 Diet

REC001 Diet

Standard Diet

11






REC002 Diet

REC001 Diet

Standard Diet

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REC002 Diet

REC001 Diet

Standard Diet

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Sunshine paper published Academic/gov’t funded trials

We’re moving towards clinical trials

Gibson, CG, 2015. Circulation.

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DEVELOPMENTPROGRAMS

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NEUROFIBROMATOSIS TYPE 2

CORNELIA DE LANGE SYNDROME

ATAXIA-TELANGIECTASIA PROGRAM 1

DIAMOND BLACKFAN ANEMIA

SPINAL MUSCULAR ATROPHY (SMN) PROGRAM 1

PEUTZ-JEGHERS SYNDROME

CEREBRAL CAVERNOUS MALFORMATION PROGRAM 1

PRE-INDIN VITRO IN VIVO

SPINAL MUSCULAR ATROPHY (UBA1)

CEREBRAL CAVERNOUS MALFORMATION PROGRAM 2

USP7- UNDIAGNOSED DISEASE

METACHROMIC LEUKODYSTROPHY/ATYPICAL GAUCHER DISEASE

10+ INDICATIONS

with CANDIDATES in ACTIVE DEVELOPMENT

ATAXIA-TELANGIECTASIA PROGRAM 2

SPINAL MUSCULAR ATROPHY (SMN) PROGRAM 2

UNDISCLOSED PARTNER INDICATION 1

UNDISCLOSED PARTNER INDICATION 2

In less than 1 year of screening

RecursionPharma.com

RecursionPharma.com

Hoechst (DNA)

RecursionPharma.com

concanavalin A (ER)

RecursionPharma.com

SYTO 14 (RNA, nucleoli)

RecursionPharma.com

mitotracker (mitochondria)

RecursionPharma.com

Combined

RecursionPharma.com

HUVEC cells instead of A549, different stain combination

RecursionPharma.com

Still HUVEC cells, different stain combination


FINDING NEW TREATMENTSINTERACTIVE DATA VISUALIZATION

Anaconda demo


Blake Borgeson Co-Founder & CTO [email protected]

Massively hiring:Data Scientists ML Researchers Software Engineers RecursionPharma.com/careers

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Blake Borgeson Co-Founder & CTO

[email protected]


anaconda-powered rapid drug discovery | anacondacon 2017

Data & Analytics