Harnessing Novel Immunobiology
April 2020
www.equilliumbio.com
Safe Harbor Statement
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Actual results or events could differ materially from the plans, intentions and expectations disclosed or implied in the forward- looking statements the Company makes due to the risks and uncertainties inherent in the Company's business, including without limitation, risk described in the Company's filings with the Securities and Exchange Commission ("SEC"). You are cautioned not to place undue reliance on these forward-looking statements, which represent the Company's views as of the date of this presentation. The Company's anticipates that subsequent events and developments will cause the its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company has no current intention of doing so except to the extent required by applicable law. These and other risks and uncertainties are described more fully under the caption "Risk Factors" and elsewhere in the Company's filings and reports, which may be
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Equillium Fast Facts
- Equillium was founded in 2017 - we aspire to build a world-class biotechnology company focused on dramatically improving the lives of patients with severe immuno- inflammatory diseases
- Headquartered in La Jolla, CA
- office in South San Francisco
- Currently developing itolizumab (EQ001) in patients with:
- acute GVHD
- uncontrolled asthma o lupus nephritis
- NASDAQ: EQ
3
Delivering
powerful new
treatment approaches
Our lead asset, itolizumab, is unique, modulating both the
activity and trafficking of Teff cells
Focused on | Driven by an |
immuno-inflammatory | accomplished team |
diseases with high | rapidly delivering key |
unmet need | milestones |
Initial clinical programs are targeting | Three clinical studies initiated 2019, |
diseases with limited or no treatment | initial data expected 2H 2020 |
options |
4
Accomplished Management Team
Bruce Steel, CFA
Chief Executive Officer
Krishna Polu, MD
Chief Medical Officer
Steve Connelly, PhD
Chief Scientific Officer
Christine Zedelmayer
Chief Operating Officer
Jason Keyes
Chief Financial Officer
Joel Rothman
SVP of Development Operations
5
Itolizumab (EQ001) First-in-class Lead Program
First-in-classanti-CD6 mAb that inhibits the activity and trafficking of
Teff cells by selectively targeting the CD6-ALCAM pathway
Broad potential 'pipeline in a product' - multiple high-value
indications applicable, three clinical studies underway
Validated therapeutic - studied in over 330 patients and approved for the treatment of psoriasis in India
Equillium acquired exclusive rights to itolizumab for the United States, Canada, Australia, and New Zealand from Biocon - partnership provides clinical & commercial product, commercial scale production at FDA regulated facility
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Itolizumab Development Strategy
Equillium is well-capitalized and staffed to execute on key programs
Indication | Phase 1 | Phase 1b / 2 | Phase 3 | Expected Milestones |
aGVHD
FDA Fast Track
Orphan Drug Designation
- EQUATE Phase 1b/2 trial underway
- Data to inform further development in GVHD, e.g. GVHD prevention, cGVHD
- Initial data expected 2H 2020
uncontrolled asthma | • EQUIP Phase 1b trial: on pause due to COVID-19 |
lupus nephritis
FDA Fast Track | • EQUALISE Phase 1b trial: on pause due to COVID-19 |
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The CD6-ALCAM Pathway
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CD6-ALCAM Pathway Central to Immuno-inflammation
APC / TISSUE | CD6 is a co-stimulatoryreceptor expressed on T cells, differentially |
expressed on subsets of innate lymphoid (ILC) and natural killer (NK) | |
cells, but not on T regulatory cells (Treg) |
Activated leukocyte cell adhesion molecule (ALCAM), is expressed on both antigen-presentingcells and endothelial/epithelial tissue including the blood-brain-barrier,skin, gut, lung and kidney
The binding of CD6-ALCAM is important for:
• Immune synapse formation
• Optimal co-stimulation and activation
• Trafficking into tissues
The CD6-ALCAM pathway modulates T cell activity and trafficking | |
T CELL | and is central to the pathogenesis of multiple immuno-inflammatory |
diseases | |
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Itolizumab Modulates CD6-ALCAM Pathway
APC / TISSUE
T CELL
Itolizumab
- Humanized IgG1 Kappa
- Binds to domain 1 of human CD6 with 1.3 nM affinity
- Inhibits ALCAM binding to CD6
- Non-depleting,modulatory action
Manufacturing and formulation
- Manufactured in CHO cells at commercial scale
- IV and SC formulations available
Dosing
- Half-lifeIV/SC @ 20/24 days respectively; target dosing of bi-weekly to monthly with potential for quarterly maintenance
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CD6 - Central Role in T Effector Cell Development
Highest levels of CD6 are found on activated T effector cells (Teff) and associated with amplification of the auto-reactive cascade
CD6 Low/- | ||||
CD6 + | CD6 Hi | |||
Th1
Th2
Th17
CD6 | |
Immune Regulatory | Autoreactive |
"Tolerance" | "Autoimmunity" |
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CD6-ALCAM Pathway Central to Immuno-inflammation
ACTIVITY | TRAFFICKING | ||||
Increased proinflammatory
cytokine secretion
Optimal immune synapse | Increased trafficking of Teff |
formation, activation | |
cells into target tissues | |
and proliferation | |
Suppression of regulatory
pathways | 12 |
Itolizumab Inhibits Pathogenic T Cell Activity & Trafficking
ACTIVITY | TRAFFICKING | ||||||
Decreased proinflammatory
cytokine secretion
Inhibits optimal synapse | Decreased trafficking of Teff |
formation co-stimulation, | |
cells into target tissues | |
activation and proliferation | |
Restoration of regulatory
pathways | 13 |
Upstream, Disease Modifying Immuno-inflammatory Mechanism
Itolizumab acts upstream and selectively targets autoreactive effector T cells, while sparing regulatory T cells to promote immune tolerance and durable disease remission
Synergistic inhibition of multiple | Inhibition of Teff trafficking into | Restoration of immune regulation | |||
Teff cells and cytokines* | key target organs | without immunosuppression | |||
Teff | Treg | ||
Teff | Teff | Teff | |
Teff | |||
Teff |
Th1 / Th2 / Th17
*including but not limited to IFN-γ,TNF-α,IL-4,IL-5,IL-6,IL-13 and IL-17 | 14 |
Clinical Strategy
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Acute graft-versus-host
disease (aGVHD)
A multisystem complication of allogeneic
hematopoietic stem cell transplants,
or allo-HSCT, caused by Teff cells, recognizing
and attacking the recipient's body
8,500
30-70%
53%
95%
0
2
1
Allo-HSCT's performed in 2016
4% procedural growth year-over-year
Allo-HSCT patients will develop aGVHD
Survival rate for steroid responders
Mortality rate for steroid non-responders
Number of approved treatments
for first-lineaGVHD
Number of products in development
for first-line aGVHD - itolizumab
Product in development that modulates both the activity and trafficking of Teff cells - itolizumab
All numbers are approximate and based on published reports | 16 |
CD6+ T Cells Drive GVHD Pathogenesis
Irradiation leads to activation of donor T cells | T cell Proliferation and secretion of proinflammatory cytokine | Activated donor T cells infiltrate tissues |
GUT
SKIN
LIVER | 17 |
Itolizumab is a Differentiated aGVHD Treatment Option
Acute GVHD
0-100 days post-transplant
Prevention | First-line | ||||||||||||||
ENTYVIO® | Itolizumab | ||||||||||||||
Alpha-1 antitrypsin | |||||||||||||||
Phase 3 | Phase 2/3 | Phase 1b/2 | |||||||||||||
BMTCTN | |||||||||||||||
DEFITELIO® | |||||||||||||||
ORENCIA® | Alpha-1 antitrypsin | ||||||||||||||
Phase 2 | Phase 3 ready | Phase 3 | |||||||||||||
Cannabidiol | Alpha-1 antitrypsin | ||||||||||||||
Itacitinib | |||||||||||||||
Phase 3 | Phase 2 | ||||||||||||||
Phase 3 (failed)
Steroid-refractory
JAKAFI®
Approved
Remestemcel-L
BLA
T-Guard™
Phase 3 ready
Itolizumab
First line positioning
- Dual mode of action inhibits the activity and trafficking of Teff cells
- Potential disease-modifying therapy with durable benefit
- Immunomodulatory vs. immunosuppressive
- No cytopenia seen in Biocon Phase 3 psoriasis studies
- Positive Phase 1b data will inform lifecycle opportunity in GVHD prevention and cGVHD
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EQUATE Study for First-line Treatment in aGVHD
Study Population: First-line treatment of newly diagnosed aGVHD patients
Study Design
Phase 1b N~24 (Grade III - IV / high-risk)
- Open-label,3x3, dose escalation
- 5 doses, bi-weekly - intravenous (IV)
Primary Objectives | Secondary Objectives | ||
• Assess the safety and tolerability of IV | • Characterize the pharmacokinetics (PK) | ||
dosing of itolizumab | and pharmacodynamics (PD) of itolizumab |
• | Determine optimal IV dose | • | Assess the clinical activity of itolizumab: | |
level(s) of itolizumab | GVHD ORR, NRM, cGVHD, durability | |||
Phase 2 N~60 (Grade II - IV) | • | Further characterize the safety, | ||
• Randomized, double-blind, placebo | • | Assess the clinical activity of itolizumab: | ||
tolerability and PD of IV dosing of | ||||
controlled | GVHD ORR, NRM, cGVHD, durability | |||
itolizumab | ||||
• 5 doses, bi-weekly - intravenous (IV) | ||||
Phase 1b initial data expected 2H 2020 | Phase 1b informs Phase 2 study as well as lifecycle |
strategy that may include GVHD prevention and cGVHD | |
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Uncontrolled moderate
to severe asthma
A heterogeneous disease characterized by different Teff cell subtypes and other innate immune cells driving both allergic and autoimmune mechanisms, leading to chronic airway inflammation
2.6mm | Severe asthma patients in the U.S. | |
1.3mm | Patients uncontrolled by standard-of-care | |
treatments (long-actingbeta-agonists, inhaled | ||
corticosteroids, oral corticosteroids) | ||
~50% | Of uncontrolled patients do not respond | |
to existing biologic treatments | ||
0 | Approved products covering the full spectrum of | |
disease (Th2 High to Non-Th2 asthma) | ||
2 | Products in development that | |
target Non-Th2 asthma | ||
1 | Product in development that modulates both the | |
activity and trafficking of Teff cells - itolizumab | ||
All numbers are approximate and based on published reports | 20 |
CD6-ALCAM Implicated Broadly in the Pathogenesis of Asthma
Type 2 Inflammation | Non-Type 2 / Th17 Inflammation |
Allergens | Irritants, pollutants, |
microbes, and viruses | |
TSLP | IL-25 | IL-33 | IL-6 | CXCL8 | ||||
CD6
Th2 |
cell |
IL-13 | CD6 | ||
IL-4,IL-5,IL-13 | ILC2 |
CD6
Th17 |
cell |
TGF-βVGM-CSF
IL-23
IFN-γ
CD6
Th1 |
cell |
TNF
IL-4 | IL-5 | IL-6,IL-17,IL-8 | ||
Teff | ||||
IL-3,IL-4,IL-5,IL-9 | ||||
B cell | IgE | |||
Mast cell | Eosinophil | ALCAM | Neutrophil |
Figure Legend: CD6 is expressed on Th1, Th2, Th17 and ILC2 effector cells that secrete multiple proinflammatory cytokines implicated in asthma | |
pathogenesis. ALCAM is expressed on antigen presentation cells that activate effector cells. ALCAM is also expressed on endothelial and | 21 |
smooth muscle cells where it plays a role in trafficking of CD6+ effector cells. Adapted from Israel E, et al., N Engl J Med. 2017;377(10):965-976. | |
Upregulation of CD6 & ALCAM in Severe Asthma Patients
Examination of gene expression datasets and lung tissue support the presence of increased CD6,
CD4 T cells, and ALCAM in the lungs of severe asthma patients
6 | * | ||||||||||||||||||||||||||
* | |||||||||||||||||||||||||||
CD6 expressionCD4 expression | |||||||||||||||||||||||||||
(log2FPKM)(log2FPKM) | 4 | ||||||||||||||||||||||||||
6.5 | * | ||||||||||||||||||||||||||
2 | ALCAM expression | ||||||||||||||||||||||||||
(log2FPKM) | 6.0 | ||||||||||||||||||||||||||
0 | |||||||||||||||||||||||||||
6 | *** | 5.5 | |||||||||||||||||||||||||
*** | |||||||||||||||||||||||||||
4 | 5.0 | ||||||||||||||||||||||||||
2 | 4.5 | ||||||||||||||||||||||||||
l | a | ||||||||||||||||||||||||||
o | |||||||||||||||||||||||||||
r | m | ||||||||||||||||||||||||||
t | |||||||||||||||||||||||||||
n | th | ||||||||||||||||||||||||||
0 | o | s | |||||||||||||||||||||||||
C | A | ||||||||||||||||||||||||||
l | |||||||||||||||||||||||||||
a | |||||||||||||||||||||||||||
t | |||||||||||||||||||||||||||
a | |||||||||||||||||||||||||||
e | e | F | |||||||||||||||||||||||||
y | |||||||||||||||||||||||||||
t | r | ||||||||||||||||||||||||||
h | a | e | |||||||||||||||||||||||||
t | r | v | |||||||||||||||||||||||||
l | e | ||||||||||||||||||||||||||
a | e | ||||||||||||||||||||||||||
e | d | S | |||||||||||||||||||||||||
H | o | ||||||||||||||||||||||||||
M | ***p<0.001, *p<0.05. | ||||||||||||||||||||||||||
- Analysis of two different gene expression datasets support the presence of increased CD6, CD4 T cells, and ALCAM in the lungs of severe asthma patients
Fatal asthma Non-asthma
•
CD6 | ALCAM | overlay |
epithelium
Lamina propria
Fatal asthma patients - lung tissue staining suggests increased numbers of CD6+ cells, upregulation of ALCAM in the lamina propria (mucosa), and co-localization of CD6+ cells with ALCAM expressing tissue
Study of the Mechanisms of Asthma (MAST; NCT00595153); Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) | 22 |
study; Data courtesy of Reynold A. Panettieri, Jr., MD, Rutgers Institute for Translational Medicine and Science |
Itolizumab May Address the Full Spectrum of Uncontrolled Asthma
Reciprocally
regulated
Th2-High | Th2-Low |
Eosinophils | Low Eosinophils |
Response to steroids
Current therapies target downstream | Current downstream therapies ineffective | |||||||||||||||||||||||||||||||||||||
signaling of Th2-associated inflammation | in patients with low levels of eosinophils | |||||||||||||||||||||||||||||||||||||
anti-IgE | anti-IL-5 | anti-IL-4 /IL-13 | anti-IL-33 | anti-CD6-ALCAM | ||||||||||||||||||||||||||||||||||
Itolizumab | ||||||||||||||||||||||||||||||||||||||
NUCALA® | RG6149 | |||||||||||||||||||||||||||||||||||||
DUPIXENT® | REGN3500 | |||||||||||||||||||||||||||||||||||||
XOLAIR® | ||||||||||||||||||||||||||||||||||||||
Marketed | Marketed | Marketed | Phase 2 | Phase 2 | Phase 1b | |||||||||||||||||||||||||||||||||
anti-TSLP | ||||||||||||||||||||||||||||||||||||||
DP2 Agonist | ||||||||||||||||||||||||||||||||||||||
CINQAIR® | GSK3772847 | Tezepelumab | ||||||||||||||||||||||||||||||||||||
Marketed | Phase 2 | |||||||||||||||||||||||||||||||||||||
GB001 | Phase 3 | |||||||||||||||||||||||||||||||||||||
inhaled JAK | ||||||||||||||||||||||||||||||||||||||
Phase 2b | ||||||||||||||||||||||||||||||||||||||
FASENRA® | ||||||||||||||||||||||||||||||||||||||
Marketed | ||||||||||||||||||||||||||||||||||||||
pan-JAK /TD-8236 | ||||||||||||||||||||||||||||||||||||||
Phase 1/2 |
Non-Th2
Neutrophils
No approved therapies
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EQUIP Study in Uncontrolled Asthma
Study Population: Uncontrolled moderate to severe asthma patients
Study Design | Primary Objectives | Secondary Objectives | ||||
Phase 1b N=32 | ||||||
• Randomized, double-blind, placebo | • Assess the safety and tolerability of | • Characterize the pharmacokinetics (PK) | ||||
controlled, dose escalation study | subcutaneous dosing of itolizumab | and pharmacodynamics (PD) of itolizumab | ||||
• 5 doses, bi-weekly - subcutaneous | • Determine optimal subcutaneous dose | • Assess the clinical activity of itolizumab: | ||||
level(s) of itolizumab | FEV1, ACQ, FeNO, Eos | |||||
Study on Pause Due to COVID-19
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Lupus nephritis
A heterogeneous disease that is the most
frequent and serious manifestation of systemic lupus erythematosus (SLE)
100,000
50%-75%
40%
0
9
Lupus nephritis patients in the U.S.
Of patients do not respond to
frontline treatments
Of severe, proliferative patients will progress to
end-stage renal disease
Approved treatments
Products in development
1 | Product in development that modulates both the |
activity and trafficking of Teff cells - itolizumab |
All numbers are approximate and based on published reports | 25 |
T Cell Directed Therapies Represent a Promising Approach
Activated APC's/dendritic cells
Effector cytokines
T | reg | Teff |
Activated
T cells play a central role in the immunopathogenesis of lupus, with aberrant T cell activation and function leading to defective peripheral tolerance
T cells also secrete pro-inflammatory cytokines, help B cells generate autoantibodies, and maintain disease through accumulation of autoreactive memory T cells
B cell directed and single cytokine approaches have previously failed in lupus nephritis in Phase 3 trials
Current T cell approaches have demonstrated promising efficacy (MMF, Cytoxan), but have significant toxicities and a narrow therapeutic index
effector cells
B cell
T cell
Teff |
B cell | Targeted Cytokine | Complement Inhibition |
C3 Complement |
Activated | |||||||||||||
B cells | KZR-616 | Anifrolumab | APL2 | ||||||||||
Itolizumab | |||||||||||||
Phase 1b | Phase 2 | Phase 2 | Phase 2 | ||||||||||
Tissue-targeting | |||||||||||||
GAZYVA® | |||||||||||||
Narsoplimab | |||||||||||||
Complement-mediated | BI 655064 | ||||||||||||
Antibodies | |||||||||||||
Phase 2 | Phase 2 | Phase 2 | |||||||||||
destruction | |||||||||||||
Voclosporine | |||||||||||||
BENLYSTA® | 26 | ||||||||||||
Phase 3 | Phase 3 | ||||||||||||
Treating Lupus Nephritis Today - Similar Treatment for All Patients
- Standard diagnostics unable to inform biological differences between patients
- All patients treated uniformly with limited choices
- Patients may be exposed to ineffective therapies
• Payers pay for treatments that are ineffective in some patients and also pay for the associated complications
27
Treating Lupus Nephritis Tomorrow - Individualized Therapy
- Biomarker driven diagnostics inform differences between patients and guide treatment
• Therapy benefit-to-risk improved for patients who may respond
• Use of ineffective treatments minimized - lower overall cost to health care system
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ALCAM is a Predictive Biomarker in Patients with Active Lupus Nephritis
Unbiased screening of >1100 urinary proteins identified urinary ALCAM as a strong predictor of disease activity
in lupus nephritis patients
Urinary ALCAM pg/mg
250000
*
200000
150000
100000
50000
0
Active
LN
Urinary ALCAM Elevated in Active
Lupus Nephritis
Distribution of ALCAM levels seen within race and disease severity
*statistical significance
* | * | |||||||
* | ||||||||
Active Non | Healthy | |||||||
Inactive SLE | ||||||||
Renal | Control | |||||||
Urinary Biomarker Outperforms Standard Disease Biomarkers in
Lupus Nephritis*
AUC | P value | Sensitivity | Specificity | PPV | NPV | ||
(95% CI) | |||||||
Urinary | 0.91 | < 0.0001 | 0.91 | 0.82 | 0.88 | 0.86 | |
ALCAM | (0.86 - 0.96) | ||||||
Positive anti- | NA | 0.38 | 0.57 | 0.57 | 0.38 | ||
dsDNA | |||||||
Low | NA | 0.56 | 0.55 | 0.65 | 0.46 | ||
complement | |||||||
*Performance of urinary protein markers in differentiating active lupus nephritis (N=89) from inactive lupus nephritis (N=60) in African American and Hispanic systemic lupus erythematosus patients - UT Southwestern Medical Center, TX
Stanley et al., 2016. Comprehensive Aptamer-Based Screening of 1129 Proteins Reveals Novel Urinary Biomarkers of Lupus Nephritis. ACR/ARHP Annual Meeting. | 29 |
EQUALISE Study in Lupus / Lupus Nephritis (LN)
Study Design | Primary Objectives | ||
Type A Cohort (SLE Patients): Phase 1b N=24 | |||
• Open-label, dose escalation in patients w/ | Type A and B Cohorts | ||
active or inactive SLE without LN | • | Assess the safety and tolerability of |
• 2 doses, bi-weekly - subcutaneous | itolizumab in subjects with SLE with and |
without active proliferative lupus nephritis | |
• Determine optimal subcutaneous dose | |
level(s) of itolizumab |
Secondary/Exploratory Objectives
Type A and B Cohorts
- Characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of itolizumab
- Understand changes in disease serologies, urinary ALCAM and CD6, CD6 receptor occupancy
Type B Cohort only
Type B Cohort (active LN patients): Phase 1b N=32
- Randomized, double-blind, placebo controlled in active proliferative LN patients w/ inadequate response to existing therapy
- 7 doses, bi-weekly - subcutaneous
- Assess the clinical activity of itolizumab: proteinuria and SLEDAI-2K
Study on Pause Due to COVID-19
30
Corporate
31
Corporate
Exclusive rights for the United States, Canada, Australia, and New Zealand, and rights to negotiate itolizumab licensing for select additional major markets, e.g. EU / Japan
Biocon partnership provides risk-mitigatedproduct supply on attractive terms
- CMC completed and itolizumab currently manufactured at commercial scale in FDA-regulatedfacility
- Drug product supplied at no cost for 3 concurrent orphan indications until first U.S. approval; all other clinical supply at cost
Robust IP portfolio and potential for 12-yearbiologics exclusivity
Strengthened balance sheet and lean operating model expected to fund current development programs into 2H 2021
Pursuing opportunities for strategic pipeline expansion
32
Summary
First-in-class: Itolizumab is the first antibody targeting the novel CD6-ALCAM pathway for the treatment of severe immuno-inflammatory disorders
Pipeline-in-a-product: Itolizumab has broad potential disease modifying therapeutic utility
Focused Development: Strong scientific rationale and translational validation supporting initial indications in areas of unmet need; multiple clinical studies launched during 2019 with initial data 2H 2020
High-valuepartnership: Biocon partnership provides clinical & commercial product, commercial scale production at FDA regulated facility
Accomplished team: Experienced in drug discovery, development and commercialization
EQ resources: Equillium is capitalized and staffed to deliver on key programs into 2H 2021
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Equillium, Inc.
2223 Avenida de la Playa / Suite 105 La Jolla, CA 92037 www.equilliumbio.comir@equilliumbio.com
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Equillium Inc. published this content on 08 April 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 08 April 2020 14:37:16 UTC