Genetic Medicines for Rare CNS Diseases OCTOBER 2019 / Company - - PowerPoint PPT Presentation

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Genetic Medicines for Rare CNS Diseases OCTOBER 2019 / Company - - PowerPoint PPT Presentation

Oct 01, 2023 127 likes •333 views

Developing Breakthrough Genetic Medicines for Rare CNS Diseases OCTOBER 2019 / Company Overview $225.5M Developing life transforming genetic medicines for the treatment of rare monogenic CNS diseases RAISED SINCE LAUNCH - Portfolio of 6

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Developing Breakthrough Genetic Medicines for Rare CNS Diseases

OCTOBER 2019

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Company Overview

Developing life transforming genetic medicines for the treatment of rare monogenic CNS diseases

  • Portfolio of 6 indications with option to license an additional 6
  • Lead programs in GM1, FTD and Krabbe disease to enter clinic in 2020

Partnership with the University of Pennsylvania Gene Therapy Program

  • Proven best-in-class AAV technology and know-how, with 8 INDs filed in the orphan

disease space

  • Includes capsids from the next generation platform
  • GTP will conduct IND-enabling preclinical work through an SRA and Passage Bio will be

responsible for clinical development, regulatory, manufacturing and commercialization

Partnership with Penn’s Orphan Disease Center to support clinical development and commercial deployment

  • Create patient registries
  • Conduct natural history studies
  • Engage with KOLs and patient alliances

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HEADQUARTERED IN

Philadelphia, PA

$225.5M

RAISED SINCE LAUNCH

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INDICATION GENE DISCOVERY IND ENABLING

CLINICAL DEVELOPMENT

Named Programs GM1

GLB1 1H 2020

FTD

PGRN 1H 2020

Krabbe Disease

GALC 2H 2020

CMT2A

MFN2 2021

Unnamed Programs Program 4

2021

Program 5

2021

Deep Pipeline of Rare Monogenic CNS Disease Therapies*

3 *Option to license 6 additional indications

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Focused on Building through Partnership

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▪ Strong preclinical translational

science and regulatory capabilities

▪ At the cutting edge of AAV research

for 20+ years

▪ AAV manufacturing expertise ▪ Fully-integrated capabilities ▪ Deep orphan drug development

and commercialization know-how

▪ Ability to select and prioritize

existing programs and nominate new programs for research

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Our Unique Therapeutic Development Process

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DISCOVERY CLINIC COMMERCIALIZATION

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All pre-clinical and IND-enabling studies

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Support for GLP toxicology

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Development of next generation capsids

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All clinical development, regulatory strategy and commercialization activities

Patient registries, natural history studies, KOL and patient engagement

PASSAGE BIO RECEIVES

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Licenses to 6 initial programs

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Exclusive option to license 6 additional programs utilizing next generation capsids PENN RECEIVES

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Upfront payment

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Royalties and milestones

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Sponsored research agreement funding

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INDICATION Passage Bio

Passage Bio Optimal Vector and Delivery Route Selection

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Intraparenchymal IV Lumbar ICV ICM Delivery

Limited Limited / Very High Doses Limited Diffuse Diffuse

Toxicity

High Systemic Low High Low

AAV Abs Impact

Limits efficacy No Impact No Impact No Impact

Procedure

Routine Interventional Radiologist Interventional Radiologist

Utilize best delivery route

SELECT OPTIMAL AAV

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Development Pipeline

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Type 1 GM1 Gangliosidosis Overview

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▪ Autosomal recessive genetic disorder, cause by inactivating mutation of the

lysosomal enzyme β-galactosidase (GLB1)

▪ Abnormal upregulation of lysosomal enzymes in serum ▪ Extensive brain storage lesions ▪ Hypotonic by 4 months of age, developmental regression by 6 months

▪ Rapid progression with mortality by ~2 years of age

▪ No disease modifying therapies currently available ▪ The estimated worldwide incidence of infantile GM1 gangliosidosis is 0.5–

1:100,000 live births

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Pharmacology Study in GLB1-/- Mice Brain HEX Activity

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*p < 0.05, **p<0.01 Kruskal-Wallis test/Dunn’s test

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Infantile GM1 Natural History Study

CONFIDENTIAL 10

Infantile NHS, onsite assessments required AGE RANGE All ages INCLUSION CRITERIA

  • Diagnosis of type 1 and 2 GM1 gangliosidosis
  • Documented symptom onset before

12 months of age

  • Documentation of homozygous GLB1

gene deletion or mutation and GLB1 activity < lower limit of normal. ENDPOINTS

  • Survival, Bayley Score and all FIH

exploratory endpoints

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Overview of Frontotemporal Dementia (FTD) Caused by Progranulin Mutations

▪ FTD typically presents around age 60-70

  • A subset of familial forms of FTD is caused by

mutations that lead to a deficiency in progranulin

  • Average survival 8 yrs. from symptom onset

▪ Shrinking of the frontal and temporal lobes of the brain

  • Causes impairment of executive function, language

and/or social interaction

▪ No disease modifying therapies currently available ▪ Goal of therapy: restore CSF PGRN levels to normal ▪ 20,000-30,000 patients with FTD (between the ages of 45-

64)1

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1Knopman 2011

  • FLAIR. Marked frontal and temporal atrophy +

periventricular white matter lesions

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Frontotemporal Dementia PGRN Preclinical Program

Evaluated potential to achieve therapeutic expression levels in a large animal model

▪ Proprietary AAV vector expressing human PGRN

administered ICM to 2 rhesus macaques

▪ Necropsy 35 days post injection ▪ CSF PGRN levels reached 5-10x those

  • f normal human subjects

▪ No abnormalities noted on weekly physical exam

  • r daily observations

▪ No significant abnormalities noted on weekly

CBC/chem, LFTs, CSF analysis

▪ No brain pathology

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Two adult rhesus macaques were treated with ICM AAV on study day 0. Human PGRN was measured in CSF by ELISA.. 10 20 30 40 0.1 1 10 100

Day RA2981 RA2982

Healthy Subjects

0.1 1 10 100

AAV Treated NHPs

CSF PGRN (ng/mL)

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Krabbe Disease Overview

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▪ Autosomal recessive lysosomal storage disease caused by mutations in the gene encoding the

hydrolytic enzyme galactosylceramidase (GALC)

▪ Global incidence: 1 in 100,0001 ▪ Destroys the myelin of nerve cells in the brain and throughout the nervous system ▪ Early infantile Krabbe disease2 ▪ Most severe, 60–70% of diagnoses ▪ Symptoms develop before 6 months of age ▪ Survival is ~2 years ▪ Late infantile Krabbe disease3 ▪ 10–30% of diagnoses ▪ Onset between 7-12 months of age ▪ Survival is ~5 years ▪ No disease modifying therapies currently available

1Escolar et al., 2016, Wasserstein et al., 2016 2Escolar et al., 2006, Duffner et al., 2011 3Duffner et al., 2012

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Krabbe Large Animal Model: Brain MRI 8 weeks Post-Treatment

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Wild type control – hypointense WM (normal = black WM) – clear corpus callosum (arrow) Krabbe vehicle #2 – hyperintense WM (arrows), cortical atrophy (star), dilated ventricle (arrowhead), corpus callosum (myelinated WM band between 2 hemispheres) is not visible Krabbe AAV ICM #2 – normal (hypo) to iso WM

  • signal. No atrophy. Normal

ventricle and normal corpus callosum

*

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iCELLis: Superior GMP Manufacturing Platform

▪ Fully-integrated bioreactor system ▪ Provides excellent cell growth conditions for

adherent cells

▪ Can handle large clinical and commercial-scale

volumes at reduced operational costs

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Dedicated cGMP Manufacturing Suite

▪ Dedicated manufacturing in Harmans, MD under strategic partnership agreement with Paragon Gene

Therapy

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cGMP suite to support future clinical and commercial production for Passage therapies

▪ Expected to be operational in second half of 2020

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Passage Bio Management Team and BOD

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Jill Quigley, J.D.

CHIEF OPERATING OFFICER

Pharmasset, NPS Pharma, Shire, Nutrinia

BOARD OF DIRECTORS

Tachi Yamada

Board Chair, Frazier

Saqib Islam

CEO of SpringWorks

Stephen Squinto

Interim CEO and OrbiMed Venture Partner

Carl Gordon

OrbiMed Advisors

Stephen Squinto, Ph.D.

INTERIM CHIEF EXECUTIVE OFFICER

Regeneron, Alexion co-founder, OrbiMed Venture Partner

Jim Wilson, M.D., Ph.D.

CHIEF SCIENTIFIC ADVISOR

Director, Gene Therapy Program and Orphan Disease Center

Alex Fotopoulos

CHIEF TECHNICAL OFFICER

Ultragenyx, Momenta Pharmaceutical, Biogen

Patrick Heron

Frazier

Tom Woiwode

Versant Ventures

Liam Ratcliffe

Access Industries

Gary Ramano, M.D.

CHIEF MEDICAL OFFICER

Janssen R&D, Merck,

Edgar (Chip) Cale, J.D.

GENERAL COUNSEL

GlaxoSmithKline, Venture Law Group, Brobeck, Phleger & Harrison

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Upcoming Milestones

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2020 2021

GM1

Clinical Development

Krabbe Disease

Clinical Development

Program 5

Clinical Development

FTD

Clinical Development

Program 6

Clinical Development

Pediatric Indications Adult Indications CMT2A

Clinical Development

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Company Overview

Developing life transforming genetic medicines for the treatment of rare monogenic CNS diseases

  • Portfolio of 6 indications with option to license an additional 6 indications
  • Lead programs in GM1, FTD and Krabbe disease to enter clinic in 2020

Partnership with the University of Pennsylvania Gene Therapy Program

  • Proven best-in-class AAV technology and know-how, with 8 INDs filed in the orphan

disease space

  • Includes capsids from the next generation platform
  • GTP will conduct IND-enabling preclinical work through an SRA and Passage Bio will be

responsible for clinical development, regulatory, manufacturing and commercialization

Partnership with Penn’s Orphan Disease Center to support clinical development and commercial deployment

  • Create patient registries
  • Conduct natural history studies
  • Engage with KOLs and patient alliances

18

HEADQUARTERED IN

Philadelphia, PA

$225.5M

RAISED SINCE LAUNCH

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Developing Breakthrough Genetic Medicines for Rare CNS Diseases

OCTOBER 2019