delivering a new generation of integrin medicines
TRANSCRIPT
Forward Looking Statements
This presentation contains “forward-looking” statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: Morphic’s or our partners’ plans to develop and commercialize oral small-molecule integrin therapeutics and Morphic’s expectations about timing and ability to commence, enroll or complete clinical studies and to obtain regulatory approvals for MORF-057 and other candidates in development, the ability ofMORF-057 to treat inflammatory bowel diseases, including ulcerative colitis or Crohn’s disease, the ability of our platform to discover additional developable candidates (including against αvβ8 and αvβ1) or suitable indications (including in solid tumors or fibrotic diseases), the potential impact of the COVID-19 pandemic and the sufficiency of our cash, cash equivalents and investments to fund our operations.
Statements including words such as “believe,” “plan,” “continue,” “expect,” “will,” “develop,” “signal,” “potential,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements.
Forward-looking statements are subject to risks and uncertainties that may cause Morphic’s actual activities or results to differ significantly from those expressed in or implied by any forward-looking statement, including risks and uncertainties related to the forward-looking statements in this presentation and other risks set forth in our filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and Morphic specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.
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Morphic: Leaders In Oral Integrin Therapies
Professor Tim Springer discovers integrin receptor class and highlights key role mediating many complex
diseases
Integrins Discovered
1990s
$4.6B in annual sales
4 approved inhibitors
All infused antibodies
Multiple failed attempts at oral integrin inhibitor
formulations
Springer Lab makes key discovery into integrin
receptor activity, catalyzes founding of Morphic to discover oral integrin
therapeutics based on unmatched structural
biology expertise
The FirstGeneration
2000s
The Next Generation
2015+
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Morphic: Building Leadership in the Oral Integrin Space
Phase 2-ready oral program replicates blockbuster IBD antibody MoA
Proprietary ‘MInT’ Platform: unmatched capabilities for oral integrin drugs
Partnerships with marquee pharmaceutical companies
Broad pipeline addressing multiple major chronic disease areas
Strong cash position and seasoned management team
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Unique Receptors: Unique Therapeutic Potential
• Only receptor to signal bidirectionally, giving them central biologic roles in complex diseases: autoimmune, fibrotic, cardio-metabolic and cancer
• Expensive, complex biologics have shown blockbuster efficacy in targeting integrins
What are integrins?
Extracellular matrix
Cytoskeleton
Inflammatorybowel
diseaseSolid
tumors
Fibrotic diseases
Now Morphic has built the platform to deliver the advantages of oral small molecule drugs to integrin targeting, with an initial focus on three major areas.
MInT: The Only Integrated Oral Integrin Platform
Unmatched structural biology expertise creates the foundation for leadership in small molecule integrin inhibitors
Know-how and development processes continually optimizing to add value and accelerate each new development program. Exclusive license with Schrodinger enables drug binding and proprietary optimization
Proprietary integrin-specific assay suite and highly informative models
Proprietary integrin structure
determination
Tunable product candidate engine
Deep integrin-specific translation
capabilities
Targeted approach to disease areas
with unmet need
Focus on indications where integrin modulation can have major therapeutic impact over standard of care, e.g. IBD, fibrotic disease and cancer
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Status
Target (Program) Indication Preclinical Phase 1 Phase 2
α4β7 (MORF-057) IBD: UC & Crohn’s Disease
Next-generation α4β7
selective inhibitorsAdditional potential GI indications: EGIDs, pouchitis, etc.
αvβ8 Solid tumors
Undisclosed target Pulmonary arterial hypertension
Undisclosed targets Multiple indications
Morphic: A Deep Proprietary & Partnered Pipeline
Proprietary Pipeline
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Partnered Programs
• $100 million upfront, $20 million option fee paid
• Undisclosed targets including antibody agonists of an integrin
MORF-057• Small molecule inhibitor of α4β7 – a well-
validated mechanism to treat IBD
• Positive phase 1 data highly supportive of rapid clinical progression
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Indications
MORF-057: First-In-Class Oral Integrin Drug for IBD
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Highly selective orally available small molecule inhibitor of α4β7,
well validated mechanism for the treatment of IBD through
approved monoclonal antibody vedolizumab
Candidate: MORF-057Occluding α4β7 blocks intestinal homing of
lymphocytes, which in turn reduces pathologic inflammation in IBD
Inflammatory bowel disease with initial focus on ulcerative
colitis
Approximately 1.6 million Americans currently have irritable bowel disease 1
Mechanism Clinical ProgramWell tolerated across 3 phase 1 trials, dose dependent and consistent PK,
α4β7 receptor saturation at 100 mg BID
No quantifiable levels of α4β1 RO observed
Phase 2 program beginning 1Q22 with open-label phase 2a, randomized controlled phase 2b trial to follow1Chrohn's and Colitis Foundation of America
α4β7 Inhibition is a Proven Mechanism to Treat IBD
Approved antibody Entyvio®(vedolizumab)
Sub-endothelial space - gut
Vascular space - blood
T-cell
a4b7
MAdCAM-1Endothelial cell
• Vedolizumab, an anti-α4β7 antibody, inhibits T-cell trafficking via well validated mechanism to treat UC and Crohn’s disease
• Since approval, >150,000 patients have received vedolizumab 1
• Vedolizumab generated $4Bsales in FY202
1Takeda press release2Global DataENTYVIO® is a registered trademark of Millennium Pharmaceuticals, Inc. 10
Phase 1 Program with Biomarkers Complete
1. SAD cohort: safety, tolerability, and PK/PD 2. Food Effect Cohort to determine PK of a single, projected clinically relevant dose3. MAD cohort: safety, tolerability, and PK/PD, including receptor occupancy data and inflammatory biomarkers two weeks BID dosing
Three-part Phase 1 Design:
Phase 1: SAD*
Phase 1: Food-effect
Phase 1: MAD**
Phase 2
5 cohorts; 6-8 HVs/cohort
2 cohorts; 4-6 HVs/cohort
3 cohorts; 6-8 HVs/cohort
Ph1 Trial Design
Format: Randomized, double-blind, placebo-controlled trialPopulation: HealthyvolunteersEndpoints: Safety, PK and PD Dosing: Single and multiple dose of MORF-057
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*SAD: single ascending dose**MAD: multiple ascending dose
2022
Phase 2a: Open label (UC)Phase 2b: Randomized control trial (UC)
Phase 1 Overview: Data Exceed Pre-defined Targets
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MORF-057 very well-tolerated in three phase 1 studies: SAD, MAD and food effect
PD profile demonstrated clear dose and time dependent α4β7 receptor occupancy and complete α4β7 saturation observed
Predictable PK profile with excellent serum exposures - at lower-than-expected doses
Clear rationale to rapidly advance MORF-057 toward approval in ulcerative colitis
MORF-057 Saturates the α4β7 Receptor in a Time and Dose Dependent Fashion
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MORF-057 achieved >95% mean receptor occupancy (RO) of the α4β7 integrin at three highest dose levels and demonstrated ability to saturate α4β7 receptor in individual subjects in dose cohorts above 25 mg
α4β7 RO vs. MORF-057 Plasma Concentration and Dose
25 50 100 150 400
0
20
40
60
80
100
Dose (mg)
abR
O
1 7 14 1 7 14 1 7 14
0
20
40
60
80
100
Day
a4b
7 R
O (
%)
25 mg BID50 mg BID100 mg BID
SAD MAD
Ray, et al, ECCO 2021
MORF-057 Pharmacokinetics are Dose-Dependent and Predictable
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0 4 8
12
144
216
288
312
316
320
324
1
10
100
1000
Time From the First Dose (hr)
Concentr
ation (
ng/m
L)
50 mg BID100 mg BID
25 mg BID
Mean Plasma Concentration of MORF-057/Time
Ray, et al, ECCO 2021
MORF-057 Achieves >90% RO at 8ng/ML
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α4β7 RO vs. MORF-057 Plasma Concentration and Dose
1 10 1000
20
40
60
80
100
5000.5
Concentration (ng/mL)
a4b
7 R
O (
%) SAD 100 mg 12 hr
SAD 150 mg 12 hr
SAD 400 mg 12 hr
SAD 25 mg 12 hr
MAD 50 mg BID D1
MAD 100 mg BID D1
MAD 25 mg BID D1
SAD 50 mg 12 hr
SAD 400 mg 36 hr
MAD 50 mg BID D14
MAD 100 mg BID D7MAD 100 mg BID D14
MAD 25 mg BID D7MAD 25 mg BID D14
1 Veny et al 2021
Changes in Lymphocyte Subsets Consistent with Activity of Approved Mabs Inhibiting α4β7
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Changes in lymphocyte migration patterns are correlated with reduced inflammation in other IBD therapeutics including vedolizumab1
P M P M P M P M
0
100
200
300
% o
f b
as
eli
ne
p=0.1508✱
p=0.0317p=0.6905
✱p=0.0317
β7hi effector
memory T cells
β7+ central
memory T cells
β7+
naive T cells
β7hi CD3-CD4-
lymphocytes
P M
0
1
2
3
CC
R9 E
xp
ressio
n
(Rela
tiv
e t
o P
red
os
e)
✱p= 0.0238
CCR9 mRNAExpression in Blood
Statistically Significant Changes in Key Pharmacodynamic Biomarkers2
• β7 high = expressing high levels of integrin β7
• β7+ = expressing β7• P =placebo• M =MORF-057; D=
day• CCR9 = inflammatory
marker
1 Veny et al, J. Crohn’s and Colitis, 2021, 441–4522Ray, et al, ECCO 2021
*statistically significant
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Statistically Significant Changes in Pharmacodynamic Biomarkers
Predose D1 D7 D14
80
90
100
110
120
β7+ Central memory T cells
p=0.0317vs Placebo
*
PLACEBO
100 mg BID
50 mg BID
25 mg BID
Predose D1 D7 D14
80
90
100
110
120
β7 high Effector memory T cells
Med
ian
%o
f b
aselin
e p=0.0303vs Placebo
*
Changes in Lymphocyte Subsets are Consistent with Activity of Approved Mabs Inhibiting α4β7
Ray, et al, ECCO 2021
MORF-057 Phase 2 Clinical Program
Phase 2a
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2022
Open label (UC)
Phase 2b Randomized control trial (UC)
Provide rapid proof of concept for MORF-057 as an α4β7 inhibitor comparable or superior to vedolizumab in patients suffering from UC
• Open label (n=35)
• 100mg BID MORF-057
• Primary endpoint: Robarts Histopathologic Index (RHI)
• Deep translational data set to inform on MOA and predictive biomarkers
Phase 2a
• Double-blind, placebo-controlled, randomized trial
• Dose ranging efficacy and safety to inform Phase 3 design
Phase 2b Randomized Controlled Trial
2023
αvβ8 Small Molecule Integrin Inhibitor Immuno-oncology Program
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Small molecule inhibitors of the αvβ8 integrin in preclinical
development
Αvβ8 Programαvβ8 inhibition suppresses
activation of TGFβ isoforms 1 and 3
IndicationsSolid tumors, which make up
approximately 90% of all adult human cancers
Mechanism DataOral inhibitor αvβ8 integrin , in
combination with anti-PD-1, drives efficacy across mouse models of
treatment-resistant breast cancer including the EMT6 and PyMT
syngeneic breast cancer models
αvβ8 Small Molecule Inhibitor Enhances Checkpoint Inhibitor Response in Immune Refractory Model
αvβ8 inhibition blocks activation of TGF-b, a key regulator of tumor formation, progression, and metastasis
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EMT6 Murine Breast Cancer Model
EMT-6 inoculation on day 0. Dosing window days 6 through 27
Preclinical Data from Oral αvβ8 Program Demonstrate Potent Anti-Tumor Response Through TGFβ Pathway
In combination with checkpoint inhibitor, αvβ8 integrin inhibitor demonstrated potent anti-tumor activity efficacy in checkpoint-resistant models of breast cancer and induced a lasting
anti tumor effect
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8 i h + i i h i
i i
i
i i
h g
i +
+ +i
+ + 8
Deep Specialist Expertise Across Management, and Board of Directors
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PRAVEEN TIPIRNENI, MDPresident and
Chief Executive Officer
BRUCE ROGERS, PhD
Chief Scientific Officer
MARC SCHEGERIN, MD
Chief Financial OfficerChief Operating Officer
Gustav Christensen, MBA Chairman Morphic Board, former CEO, Dyax
Timothy Springer, PhD Founder, Morphic Therapeutic, Member of Morphic Scientific Advisory Board; Latham Family Professor, Professor of Biological Chemistry and Molecular Pharmacology; Professor of Medicine, Harvard Medical School
Norbert Bischofberger, PhD President & CEO, Kronos; EVP R&D, CSO, Gilead
Martin Edwards, MD Chairman, Kalvista; Senior Partner, Novo Holdings
Nisha Nanda, PhD Chief Development officer, Loxo at Lilly
Amir Nashat, PhD Managing Partner, Polaris Partners
Susannah Gray, PhD Former CFO, Royalty Pharma
Joseph P. Slattery, CPA Former CFO, Transenterix, Baxano, Digene
Praveen Tipirneni, MD President and CEO Morphic Therapeutic
BOARD OF DIRECTORS
WILLIAM DEVAULGeneral Counsel and Secretary
Morphic: Building Leadership in the Oral Integrin Space
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Phase 2-ready oral program replicates blockbuster IBD antibody MoA
Proprietary ‘MInT’ Platform: unmatched capabilities for oral integrin drugs
Partnerships with marquee pharmaceutical companies
Broad pipeline addressing multiple major chronic disease areas
Strong cash position and seasoned management team
Morphic: A New Chapter In Integrin History
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1990 2000 2010Heavy Big Pharma Investment
Phase III failures for oral drugs
Drug withdrawal
Heavy Springer Lab Investment2015
Springer discoversintegrins
Morphic founded on Springer IP for oral integrin drug design
Entyvio® approved
3 non-oral approvals
2021
Morphic oral candidates enter clinic
2020
MORF-057 PoC
Integrins: Conformation is Key to Function
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• Integrins shift between an open and closed conformation
• Morphic develops ig k “h h ” i g i f i i
• Previous oral integrin inhibitors locked conformation in a “diseased” active state, leading to clinical failures
• This was a key discovery of the Springer Lab that led to the first small molecules targeting conformational change, and the formation of Morphic
Closed Open
Morphic Integrin Technology (MInT) Platform
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Tunable Product Candidate Design Engine
• Unique and well characterized library of integrin small molecules
• Exclusive Schrödinger Computational Chemistry Collaboration
• In Vitro Integrin Assay Panels
Biology and Disease Translation Capability
• Proprietary assay design
• Building a deep understanding of integrin biology in human diseases
• sophisticated and comprehensive suite of in vitro, ex vivo, and disease-specific in vivo assay
Proprietary Integrin Structure Determination
• World-leading integrin structure capabilities
• Insights initiated at Springer Laboratory
• >300 Crystallized Integrin Structures
Morphic has already delivered accelerated discovery work by leveraging insights from early programs: each iteration augments our chemistry and biology knowledge.
MORF-057 Has Inherently High Selectivity for α4β7 Versus Other Integrins
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α4β7
MAdCAM-1
α4β1
Endothelial cell
Leukocyte
Inhibiting VCAM-1
brings risk of PML
VCAM-1• MORF-057 is highly selective for α4β7 over α4β1 in cell
adhesion assays in 50% human serum (over 3 orders of magnitude)
• MORF-057 was designed to be a potent and selective oral inhibitor of the integrin α4β7 and not α4β1, a related integrin
MORF-057
Inhibitorα4β7 IC50
a
RPMI8866 MAdCAM in 50% serum
α4β7/α4β1
Fold selectivity
MORF-057 1.2 nM >3,000
Vedolizumab 0.035 nM >3,000
Natalizumab 0.166 nM 1-12
AJM300 93 nM 8-45
Etrolizumab 0.019 >106
a Cell line characteristics: Jurkat cells have been traditionally used for specifically assessing α4β1 potency, as these cells do not express α4β7. RPMI8866 cells have lower levels of α4β1 that likely better approximate expression levels in human blood. DDW 2020, Morphic Therapeutic, Jamie Wong, ePoster Tu1283
MORF-057: Key Preclinical Data
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RO NHP data
Chronic toxRO measured at Ctrough
in non-human primates dosed with selective α4β7
inhibitor, MR-5288, a tool compound related to MORF-057
In mouse gut homing assay, MORF-057 inhibits T Cell homing with equivalent potency as an α4β7 antibody
B.)The performance of the RO assay for α4β7 (A) and α4β1 (B) is similar between NHV and UC patients. Data are ± SD
A.)
MORF-057
Cell surface α4β7
Fluorescently labeled MAdCAM-based probe that competes with MORF-057
No signal, fully occupied
RO Analysis