Full Press Release Details
Forward-Looking Statements This presentation contains forward-looking
statements about Equillium, Inc. (the Actual results or events could differ materially from the plans, intentions and "Company"). In some cases, you can identify forward-looking statements by expectations disclosed or implied in the
forward-looking statements the the words "will," "expect," "intend," "plan," "objective," "believe," "estimate," Company makes due to the risks and uncertainties
inherent in the Company's "potential," "continue" and "ongoing," or the negative of these terms, or other business, including without limitation, the risks described in the Company's filings comparable
terminology intended to identify statements about the future. with the Securities and Exchange Commission ("SEC"). You are cautioned not These statements are based on Company management's current beliefs and to place undue reliance
on these forward-looking statements, which represent expectations. These statements include but are not limited to statements the Company's views as of the date of this presentation. The Company regarding the Company's business strategy,
the Company's plans to develop anticipates that subsequent events and developments will cause its views to and commercialize its product candidates, the safety and efficacy of the change. However, while the Company may elect to update these
forward- Company's product candidates, the Company's plans and expected timing looking statements at some point in the future, the Company has no current with respect to regulatory filings and approvals, size and growth potential of
intention of doing so except to the extent required by applicable law. These the markets for the Company's product candidates and cash runway. These and other risks and uncertainties are described more fully under the caption statements
involve known and unknown risks, uncertainties and other factors "Risk Factors" and elsewhere in the Company's filings and reports, which may that may cause the Company's actual results, levels of activity, performance be
accessed for free by visiting EDGAR on the SEC web site at www.sec.gov or achievements to be materially different from the information expressed or and on the Company's website under the heading "Investors." All forward- implied by
these forward-looking statements. The Company may not actually looking statements are qualified in their entirety by this cautionary statement. achieve the plans, intentions or expectations disclosed in its forward-looking This caution is made under
the "safe harbor" provisions of Section 21E of the statements, and you should not place undue reliance on the Company's Securities Exchange Act of 1934, as amended. forward-looking statements. Trademarks This presentation may
contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this
presentation may be listed without the TM, SM or symbols, but Equillium will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and
Today's Agenda Speakers Welcome: Pipeline Overview Guest Speaker
Bruce Steel, CEO Arash Mostaghimi, M.D., M.P.A., M.P.H. Associate Professor of Dermatology Powerful Multi-Cytokine Platform Harvard Medical School Steve Connelly, CSO Director, Inpatient Consultation Service, Department of Dermatology Brigham and
Women's Hospital EQ101: A First-in-Class Tri-Specific Inhibitor of IL-2, IL-9 & IL-15 Equillium Management Steve Connelly, CSO EQ101: Clinical Program Targeting Alopecia Areata Bruce Steel, C.F.A. Chief Executive Officer Maple Fung, CMO
Arash Mostaghimi, Harvard University & Brigham and Women's Hospital Closing Remarks Steve Connelly, Ph.D. Bruce Steel, CEO Chief Scientific Officer Q&A Maple Fung, M.D. Chief Medical Officer 3
Equillium Snapshot & Investment Highlights First-in-Class Immunology
Assets Leaders in Novel Multi-Cytokine Partnership for Inhibitors immunobiology Itolizumab Developing high-impact, novel therapeutics to Multiple Multiple treat autoimmune and Clinical Stage Near-term Programs Catalysts inflammatory disorders
Expected Cash Runway Into 2025 4
Diversified Pipeline of First-In-Class Immunology Assets Drugs
Indication Pre-Clinical Phase 1 Phase 2 Phase 3 Partners Anticipated Milestones EQ101 Q4 2023 initial data PoC data & FDA/EMA Orphan Worldwide IL-2/9/15 alopecia areata rights Drug Designations for CTCL Mid-2024 topline data inhibitor Q4 2023
SAD/MAD data Potential EQ102 Worldwide IL-15/21 celiac disease expansion into other 2024 celiac disease rights inhibitor GI indications patient data Multi- opportunities in autoimmunity, Worldwide Cytokine inflammation & oncology rights Platform
acute graft-versus-host FDA Fast Track & 2024 interim review disease Orphan Drug Designations EQ001 FDA Fast Track systemic lupus erythematosus itolizumab Early 2024 topline data (SLE) / lupus nephritis (LN) Designation for LN & anti-CD6
ulcerative colitis Conducted by Biocon in India 5
Anticipated Milestones EQ101 - Phase 2 Clinical Study Alopecia
Areata - Initial Data Q4 2023 Alopecia Areata - Topline Data Mid-2024 EQ102 - Phase 1 Clinical Study SAD / MAD (healthy volunteers) - Data Q4 2023 Celiac Disease - Data 2024 Itolizumab - Phase 1b / Phase 3
Clinical Studies Lupus Nephritis EQUALISE Study (Phase 1b) - Topline Data Early 2024 aGVHD EQUATOR Study (Phase 3) - Interim Review 2024 6
Itolizumab First-in-Class immune- modifying mAb targeting the CD6-ALCAM
Ono Pharmaceutical: High Value Strategic Partnership Equillium receives
upfront payment and full funding of itolizumab R&D in exchange for Ono exclusive option to purchase Equillium's rights to itolizumab Closing payments*: $38.2M Option exercise payment**: $35.1M Milestone payments: $101.4M Option period
expires three Itolizumab development and funding: months following delivery of: Equillium to continue conducting all itolizumab R&D topline data from the EQUALISE Ono to fund all R&D expenses from July 1, 2022 study
in lupus nephritis, and through the option period interim data from the EQUATOR R&D budget approximately $8M per quarter study in acute GVHD Milestone Payments up to $101.4M: Clinical Regulatory First sale
* Includes upfront payment of $26.4M and R&D expense reimbursement for the period July 1 through December 31, 2022. 8 ** 5.0B subject to currency exchange rate at the time of payment (USD amount above is based on the exchange rate as of
August 8, 2023); milestone payments and R&D reimbursement are based in USD.
Multi-Cytokine Platform & Therapeutic Candidates 9
The Multi-Cytokine Problem Cytokines leverage shared receptors
exhibiting overlapping or synergistic biological activities which presents unique drug development challenges when treating disease Cytokines often exhibit Cytokines signal via Upstream shared receptor Overlapping
signaling' signaling hubs overlapping biological Targets include Dupixent activities Downstream divergent Synergistic signaling' kinase cascades combine to create biological activities Targets include JAK inhibitors
Challenges in Targeting Cytokine Signaling Ideal Therapeutic Approach
mAb JAK inhibitor Selective inhibition of disease driving cytokines Inhibits Only One Cytokine Inhibits 50+ Cytokines Inhibiting the right Upstream combination of signaling cytokines is key for optimal therapeutic effect, balancing both Downstream
potent activity and signaling potential toxicities Inhibition too Narrow Inhibition too Broad Optimal Therapeutic Effect Other Cytokines Involved, Non-selective cytokine targeting leads leads to insufficient activity to broad immunosuppression and
Multi-Cytokine Platform Modular platform generates products that
modulate the natural biological redundancy or synergy of cytokines affording greater therapeutic benefit Validated Disease Technology originating from Products can be flexibly Targets the National Institutes of Health modified to
optimize Computational Functional therapeutic profile and tissue Biology Fusions Uniquely targets upstream targeting properties shared receptors to selectively Drug modulate multiple cytokine Broad IP portfolio covering Products
pathways in a single novel the platform, methods of product treatment and composition Structure In-silico Activity of matter design Relationships Intravenous, subcutaneous and oral delivery Protein Engineering 12
IL-10 IL-29 IL-2 Shared Receptors are Key Signaling Hubs Shared
receptors play a critical role in orchestrating important biological functions Auto-immune, inflammatory, and Wound healing anti-tumor responses & tissue regeneration IL2 / Suppression of IL-10 15R IL-27 Inflammation IL-6R R
R inflammation & fibrosis IL2 / IL-21R IL-28 IL-22 15R R R IL-12 IL-11R R c IL-10 gp130 R LIFR OSMR IL-4R IL-7R IL-28 IL-20 R R IL-9R IL-28
IL-13R TSLPR LIFR LIFR R Pathogen and anti-viral responses Skin, lung, and gut inflammation and allergy 13 IL-9
Products of the Multi-Cytokine Platform Shared receptors offer
opportunity to more effectively MULTI-CYTOKINE ACTIVATOR (MCa) modulate biology Engineered proteins that engage multiple signaling pathways to modulate biological function MULTI-CYTOKINE INHIBITOR (MCi) Engineered peptides or proteins
that block multiple signaling pathways to modulate biological function 14
C Receptor: A Key Shared Cytokine Signaling Hub Cytokines of the
C receptor are critical regulators of immune responses thus, making it an attractive drug target for modulating T, NK and B cells Synergistic signaling Overlapping Signaling on CD8 cytotoxic T cells on CD8 & NK T cells
Private Shared Receptor Receptor 15
IL-15 at the Apex of Tissue Specific Immuno-inflammation Approaches to
Targeting IL-15 EQ101 & EQ102 Initiates proinflammatory cascade preceding expression of TNF and other key cytokines IL-15 play pathogenic roles in diverse organ-specific autoimmune disorders IL-15 stimulates
generation of NK, NK-T, , ILC1, and memory CD8 T cells Diverse approaches in development to block IL-15 16 Waldmann et al., JEM., 2019
Generation of Selective Multi-Cytokine Inhibitors (MCi)
CYTOKINE-RECEPTOR COMPLEX CYTOKINE D-HELICES FUNCTIONAL FUSIONS Cytokine Shared PK extension strategies receptor Private PEGylation receptor Lipidation FC-fused peptibodies native sequences Oral delivery Peptide Stapling
Multi-specific molecules proprietary composite sequence Fc-fusions - peptibodies B mAb-fusions - bi/tri-specific Helices A & C A interact with the private receptor, D while helix D C interacts with shared receptor OPTIMIZED
MCi THERAPEUTIC engineered multi-cytokine inhibitor 17
MCi MoA: Disrupting Assembly of the Receptor Complex Selective
inhibition of cytokines A, D & F Cytokines E A D C F Multi-cytokine B A Inhibitor (MCi) A No Signaling Private Shared Receptors Receptor A B C D E F Cytokines E Control +MCi Cytokines first bind to private receptor MCi binds to c receptor
with high affinity, then transiently dimerize with and selectively blocks the c shared receptor at lower affinity that signaling of only selected leads to signaling cytokines e.g., A, D & F Signaling 18 % Inhibition
The Multi-Cytokine Inhibitor Advantage Addressing limitations of
single-target biologics and broadly immunosuppressive kinase inhibitors by selectively inhibiting only those cytokines driving disease mAb JAK inhibitor MCi Improved Therapeutic Profile Inhibits One Cytokine Inhibits 50+ Cytokine Inhibits selected
cytokines Targets undruggable sites not possible with mAb or small molecules Upstream Optimized targeting - not signaling too narrow / not too broad Increased selectivity over JAKi can afford improved safety profile
Downstream Greater potency by signaling inhibiting downstream signaling of targeted cytokines 19 Insufficient Activity Safety Liabilities Optimal therapeutic effect
Differentiated Pipeline of First-in-Class Multi-cytokine Agents EQ101
EQ102 EQ302 EQ400 Series Phase 2/3 In Phase 1 Pre-clinical Pre-clinical PEGylated peptide inhibits: PEGylated peptide inhibits: Stabilized peptide inhibits: Protein activates: IL-X + IL-Y IL-15 + IL-21 IL-2 + IL-9 + IL-15 IL-15 + IL-21 Celiac
Disease Oncology Cutaneous T Cell Celiac Disease Lymphoma Inflammatory Bowel Disease Vaccine Adjuvants Inflammatory Bowel Disease Alopecia Areata Type 1 Diabetes Potential use in combination Orally-delivered, with checkpoint inhibitors, Vitiligo SLE
locally-acting peptide ADC or cell therapy Rheumatoid Arthritis Hepatic disease approaches both in-vivo and ex-vivo Myositis Administered by Interstitial Lung Disease sub-Q injection IV injection and sub-Q IV injection with sub-Q delivery in
development 20 SLE = systemic lupus erythematosus; ADC = antibody drug conjugate
EQ101 First-in-Class Tri-specific Inhibitor of IL-2/IL-9/IL-15
EQ101: A First-in-Class Tri-Specific Cytokine Inhibitor Inhibition of
the key cytokines IL-2, IL-9 and IL-15 by EQ101 translates from preclinical models into humans IL-9 IL-15 IL-2 IL-2 & IL-15 are important PEGylated peptide As effective as ruxolitinib Significant clinical to CD8
and NK cell (based on the D-helix) in inhibiting multiple experience in >100 biology, IL-9 contributes to selectively inhibiting IL-2, lymphoproliferative or subjects, demonstrated 1 2,3 inflammation in the skin IL-9 & IL-15 signaling
leukemic T-cell lines favorable safety and 5,6 tolerability Important to inhibit both Administered as a low More effective than IL-2 and IL-15 due to volume intravenous push, ruxolitinib in mouse Positive proof-of-
redundancy in signaling with a sub-cutaneous model of immune- concept achieved on cytotoxic CD8 T cells formulation in mediated hair loss / in cutaneous T cell 4 6 development alopecia areata lymphoma patients 22 1) Nata et al., J. Biol. Chem.,
2015; 2) Massoud et al., PNAS, 2015; 3) Wang et al., Leukemia, 2018; 4) Azimi et al., AHRS, Orlando, Florida, 20185) Frohna et al., J. Clin. Pharm., 2019 6) Querfeld et al., Blood, 2019
EQ101: More Complete Downstream Signal Inhibition Versus JAKi JAKi
suppression of cytokine signaling is incomplete, while EQ101 inhibits the multiple downstream pathways for complete suppression of cytokine signaling Ruxolitinib blocks EQ101 blocks all JAK/STAT pathway only major pathways +IL-2 +IL-2 + IL-2
- + IL-2 - + rux + EQ101 pSTAT-3 pSTAT-3 pSTAT-1 pSTAT-1 pSTAT-5 pSTAT-5 pERK pERK pPI3K pPI3K Vinculin Vinculin 23 In-house data and Frohna et al., Alopecia Areata Research Summit, New York, New York, 2018
EQ101 Performs Similarly to JAK Inhibition in IL-15 Driven ATL Model
IL-2, IL-9 & IL-15 are overexpressed in adult T cell leukemia (ATL) and cutaneous T cell lymphoma 1,2,3,4,5 (CTCL) where they drive cancer cell proliferation and increased inflammation in the skin Blocking IL-2 or IL-15 alone was ineffective in
treating large granular lymphocytic 6 7 leukemia (LGLL) and ATL control PBS EQ101 EQ101 ruxolitinib 40mg/kg, IV, BIW, 4 weeks ruxolitinib continuous administration, 50mg/kg/d 24 1) Dobbeling et al., Blood,1998; 2) Mishra et al., Clin. Cancer Res.,
2014; 3) Qin et al., 2001; 4) Garcia et al., 2016; 5) Waldmann et al., 1993; 6) Waldmann et al., 2013; 7) Berkowitz et al., 2014; 8) Wang et al., 2018
EQ101: Summary of Historical Studies to Date Study BNZ-CT-101, Phase 1
Study in Healthy Volunteers (n=18) First-in-Human study to investigate the safety, tolerability and PK of single ascending doses of BNZ132-1-40 3 subjects per treatment group Single IV dose of 0.2 mg/kg, 0.4 mg/kg, 0.8 mg/kg, 1.6
mg/kg, 3.2 mg/kg, 6.4 mg/kg Study BNZ-CT-102, Phase 1 Study in Healthy Volunteers (n = 25, treated) Single center, randomized, single-blind, placebo controlled, multiple-dose study to characterize the safety, tolerability & PK/PD of IV
BNZ132-1-40 Subjects dosed weekly (QW) for 4 doses, or once every other week (QOW) for 3 doses 3 QW cohorts of 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg 2 QOW cohorts of 2 mg/kg and 3.0 mg/kg Study BNZ1-CT-201, Phase 1/2 Dose
Ranging Study in Patients with LGLL or CTCL (n = 50) Open-label, multi-center study to characterize the safety, tolerability, preliminary efficacy, and PK/PD of up to four dose levels of BNZ-1 administered QW by IV infusion Treatment on Days
1, 8, 15, and 22 followed by 3-month treatment extension period, during which subjects received up to 13 doses administered QW for a maximum of 17 weekly doses of BNZ-1 4 cohorts dosed between 0.5 mg/kg and 4 mg/kg 25 Froha et al., Journal
of Clinical Pharmacology 2020; Querfeld et al., presentation at ASH 2020; Brammer et al Blood 2023 BNZ-1 = EQ101, PK = pharmacokinetic, PD = pharmacodynamic, IV = intravenous, LGLL = Large Granular Lymphocytic Leukemia, CTCL = Cutaneous T Cell
EQ101: Summary of Experience in Normal Healthy Volunteers
No AE >= Grade 3, most common AE Dose proportional PK with Observed to be safe and SAD: mild headache in 3 of 18 subjects (17%) single dose half-life in well tolerated, no DLT and MAD: sore throat and headache in 4 of 24