ANTHONY COYLE PRESIDENT AND CEO - Jefferies Group · Unique Profile of MAdCAM-Tethered PD-1 Agonist Bispecific, PT001: anti-MAdCAM scFv: PT001. anti-PD-1 agonist IgG. Identified rare

ANTHONY COYLEPRESIDENT AND CEO

PANDION THERAPEUTICS

Pandion’s Vision

Inflamed Tissue

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Tumors provide an example of durable, localized immune -modulation

Radically shifting the paradigm from systemic immunosuppression to tissue-specific immunomodulation

Pandion is harnessing knowledge of tumor immunology to develop novel therapeutics

Creating a new generation of bispecific antibodies with transformative efficacy and improved safety for a wide array of autoimmune and

inflammatory diseases

Tumor Inflamed Tissue


$58M Series A closed January 2018

Highly Experienced Founders and Investors

Alan Crane, Co-Founder and ChairmanBiotech Entrepreneur and Investor

• Polaris Partners: Partner and Entrepreneur• Momenta, Millennium• Founder/CEO of 7 companies, 6 exits

Founders & Management Team

Tony Coyle, Co-Founder and CEOPharma and Biotech Leader, Immunologist

• Pfizer: SVP Center for Therapeutic Innovation• Medimmune/AZ: VP, Immunology; Millennium• 11 programs to clinic

Jo Viney, Co-Founder and CSO Biotech Leader, Drug-Hunting Immunologist

• Biogen: SVP, Drug Discovery; VP, Immunology• Amgen, Immunex, Genentech• 11 programs to clinic

David Sachs, Co-Founder and AdvisorInnovative Immunology Leader

• MGH, Columbia• Discovered MHC Class II and developed first

protocol for human transplant tolerance

• Nancy Stagliano, Independent Director• Gerald Nepom, Immune Tolerance Network• Diane Mathis, HMS, BWH• Scott Snapper, HMS, Boston Children’s, BWH• Ananda Goldrath, UCSD• Deborah Dunsire, Lundbeck• JC Gutierrez-Ramos, Cogen Therapeutics

Investors Advisors

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Our Core Strategy and Platform: Tissue-Specific Tethering Combined with Immune-Modulatory Effectors

Effector Moiety

Tissue Tether

Tissue-specific targeting of effector molecules

To allow immune modulation locally at site of inflammation

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Over the last 18 months, we have generated novel protein therapeutics for multiple disease indications and will advance our first compound into the clinic this year


Our Initial Focus with Tissue-Specific Tethered mAbs will be Autoimmune and Inflammatory Diseases of the Gut and Liver

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Ulcerative Colitis (UC) and Crohn’s Disease (CD)• Most approved therapeutics as well as drugs in

development induce remission in only ~30% of patients• Durable remission (maintenance at 12 months) is achieved

in only ~30% of patients; relapse is common

Autoimmune Hepatitis (AIH) and Primary Sclerosing Cholangitis (PSC) • AIH patients require lifelong immunosuppressive therapy and

some do not respond at all • No therapies currently available for PSC; only option is liver

transplantation


Creating Value With Tissue-Targeting Core Platform Approach and Untethered Immunomodulatory Molecules

Bring the next generation of safe and effective antibody drugs for autoimmune and inflammatory disease treatment to patients

Core Strategy and PlatformTethered Immune Modulators

Near-Term Value Driver:Untethered Immune Modulators

• Developing innovative tissue-targeting bispecific antibody therapeutics

• Potential to shift the paradigm in the treatment of autoimmune and inflammatory disease

• Multiple programs advancing to the clinic

• Capitalized on novel discoveries made while pursuing the innovative core platform

• Enhances near term R&D efforts and supports transition to being a clinical stage company

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Program Early-stage Discovery Late-stage Discovery Preclinical Clinical Phase 1/2

Multiple Organ

(untethered)

Gut/Liver Tethered

Skin Tethered

Kidney Tethered

Pancreas Tethered

Pandion’s Pipeline

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IND FilingQ4’19

DC NominationQ3’19

DC NominationQ1’20

POMQ4’20

IND FilingQ1/Q3’21

Current Series A financing will allow us to demonstrate

proof of mechanism in the clinic,

advance a second compound to IND, and select a third

compound for IND-enabling activities

Raising additional capital will allow us to maximize the full potential of our pipeline


MAdCAM-Based Tethering of Immune Effector Molecules Allows Targeting to the Gut and Liver

Effector Moiety

Anti-MAdCAMtether

MAdCAM is expressed on high endothelial venules

(HEV) in the gut and inflamed liver

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Tissue-specific tethering of effector molecules

To drive immune modulation in the gut and inflamed liver

Identified triple species cross-reactive, non-blocking MAdCAM

antibodies for tether component of bispecifics

MAdCAM-tethered bispecific localizes to HEV in inflamed intestine after in vivo dosing


Tissue-specific inhibition of effector

cells

Tissue-specific expansion of regulatory

cells

Dysregulated Immune Environment

Two Complementary Approaches to Restore Local Immune Homeostasis

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Anti-PD-1 Agonist

MAdCAM

IL-2 Mutein

MAdCAM

PT001 PT002


Unique Profile of MAdCAM-Tethered PD-1 Agonist Bispecific, PT001

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Tethered Agonist Assay(Jurkat reporter: recruitment of SHP-2)

[test article]

Benchmark AgonistPT001 bispecific PND120TTJ2 –ve ctrl

Antagonist Assay(Jurkat reporter: inhibition of SHP-2 recruitment)

[test article]

T B P

TTJ2 –ve ctrlBenchmark AntagonistPT001 bispecific PND119


MAdCAM-Tethered PD-1 PT001 Bispecifics Specifically Localize to HEV in Gut After SC Dosing in Mice

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The pre-optimized MAdCAM-tethered PD-1 bispecific (but not untethered PD-1 bispecific) localizes in vivo to HEV in the intestine after SC dosing in mice with colitis

MAdCAM-tethered PD-1 bispecificUntethered PD-1 bispecific


Unique Profile of MAdCAM-Tethered PD-1 Agonist Bispecific, PT001

anti-MAdCAM scFv

PT001

anti-PD-1 agonist IgG Identified rare PD-1 antibodies that are:

• Agonists when tethered, but not agonists when in solution

• Not antagonists

• Species cross reactive including some that are triple species cross reactive

Created PT001 bispecific molecules by pairing proprietary PD-1 agonist IgG component with proprietary MAdCAM scFv tether

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Currently undergoing further optimization and on track for candidate nomination Q1 2020


Pandion’s IL-2M Selectively Activates Treg In Solution and Maintains Selectivity When Tethered as a Bispecific to mMAdCAM-Expressing CHO Cells

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Tconv

Treg

pSTAT5 induction

mMAdCAM-CHO CHO (neg ctrl)

TTJ2:IL-2M (1 nM)MECA89:IL-2M (1 nM)MECA89:IL-2M (10 nM)MECA89:IL-2M (100 nM)MECA89 (10 nM)

Pandion’s IL-2M selectively activates Treg in vitro(pSTAT-5, hPBMC)


PT002 Attenuates TNBS-Induced Colitis in Humanized Mice

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PT002 attenuates weight loss in humanized mouse model of TNBS colitis

EthanolVehicleLD IL-2 (QD)PT002 (QW)

Human CD34+ HSC

16 weeks

TNBS Sensitization

1 week

TNBS Enema

3 days

Analysis

NSGWeight

lossPT002 PT002

Goettel et al., Cell Mol Gastroenterol Hepatol, 2019

IL-2 mutein

Gut Tissue tether

PT002


Unique Profile of MAdCAM-Tethered IL-2 Mutein Bispecific, PT002

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IL-2 mutein

PT002

anti-MAdCAM IgG

Developed a novel IL-2 mutein that selectively activates and expands T regulatory cells without activating or expanding other cell types

Created PT002 bispecific molecules by pairing proprietary MAdCAMIgG tether with IL-2M

Efficacious in humanized mouse colitis model

Currently undergoing further characterization and on track for candidate nomination Q3 2019


Creating Value With Tissue-Targeting Core Platform Approach and Untethered Immunomodulatory Molecules

Bring the next generation of safe and effective antibody drugs for autoimmune and inflammatory disease treatment to patients

Core Strategy and PlatformTethered Immune Modulators

Near-Term Value Driver:Untethered Immune Modulators

• Developing innovative tissue-targeting bispecific antibody therapeutics

• Potential to shift the paradigm in the treatment of autoimmune and inflammatory disease

• Multiple programs advancing to the clinic

• Capitalized on novel discoveries made while pursuing the innovative core platform

• Enhances near term R&D efforts and supports transition to being a clinical stage company

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In Vitro Activity and Selectivity of Pandion’s IL-2M, PT101

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PT101

IL-2 mutein

PT101 selectively activates human and cynomolgus monkey Tregs In vitro

[PT101] [PT101] [PT101]

[WT IL-2] [WT IL-2] [WT IL-2]

PT101

WT IL-2

Cyno T cells

Cyno T cells


• PT101 is a proprietary cytokine-Fc fusion protein comprised of a novel and unique IL-2M

• Patent published January 2019

• IND to be submitted by end of 2019; favorable pre-IND feedback from FDA; Master Cell Bank established, ready for GMP production; GLP Tox study to start in June

• Proof of mechanism in healthy volunteers by H2 2020 and patients by H1 2021

The Development of a Novel and Proprietary IL-2 Mutein, PT101, for Multiple Autoimmune and Inflammatory Diseases

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PT101

IL-2 mutein

PT101 creates significant value for Pandion and accelerates progression to being a clinical stage company


• Mission: To revolutionize the treatment of autoimmune and inflammatory diseases by shifting the paradigm from systemic immunosuppression to tissue-specific immunomodulation through our proprietary bispecific antibody therapeutics

• We have made significant progress in designing, optimizing and advancing a novel pipeline of protein therapeutics across multiple diseases

• Team: Led by a group of biotech and pharma veterans

• Pipeline: PT101 IND Q4 2019; additional IND(s) H1 2021; innovative portfolio focused on multiple disease areas

• Financing: $58MM Series A closed January 2018 with a strong syndicate; seeking to close a second round of financing in the next 1-2 months to maximize the full potential of our pipeline

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Summary

Documents

ANTHONY COYLE PRESIDENT AND CEO - Jefferies Group · Unique Profile of MAdCAM-Tethered PD-1 Agonist Bispecific, PT001: anti-MAdCAM scFv: PT001. anti-PD-1 agonist IgG. Identified rare