Full Press Release Details
Forward-Looking Statements Ventyx Biosciences, Inc. ("we,"
"us," "our," "Ventyx," or the "Company") cautions you that statements contained in this presentation regarding matters that are not historical facts are forward-looking statements. These statements are
based on the Company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: clinical development plans and related timing for Ventyx's product candidates; anticipated
timing of data announcements; anticipated efficacy, safety, dosing and clinical differentiation of Ventyx's product candidates; potential indications for Ventyx's product candidates; market opportunities; the anticipated timing of IND
submission for VTX3232; projected catalysts relating to Ventyx's product candidate pipeline; and anticipated cash runway. The inclusion of forward-looking statements should not be regarded as a representation by Ventyx that any of its plans
will be achieved. Actual results may differ from those set forth in this presentation due to the risks and uncertainties inherent in Ventyx's business, including, without limitation: potential delays in the commencement, enrollment and
completion of clinical trials; disruption to our operations from the ongoing global outbreak of the COVID-19 pandemic, including clinical trial delays; the Company's dependence on third parties in connection with product manufacturing,
research and preclinical and clinical testing; the results of preclinical studies and early clinical trials are not necessarily predictive of future results; supply chain constraints; the success of Ventyx's clinical trials and preclinical
studies for its product candidates; interim results do not necessarily predict final results and one or more of the outcomes may materially change as the trial continues and more patient data become available and following more comprehensive audit
and verification procedures; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval and/or
commercialization, or may result in recalls or product liability claims; Ventyx's ability to obtain and maintain intellectual property protection for its product candidates; Ventyx may use its capital resources sooner than it expects; and
other risks described in the Company's prior communications and the Company's filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in the Company's Quarterly Report on
Form 10-Q filed on November 4, 2022, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Ventyx undertakes no obligation to update
such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own
estimates of potential market opportunities. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the
accuracy or completeness of such information. Our estimates of the potential market opportunities for our products include several key assumptions based on our industry knowledge, industry publications, third-party research and other surveys, which
may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reliable, such assumptions have not been verified by any third party. The industry in which we operate is
subject to a high degree of uncertainty and risk due to a variety of important factors that could cause results to differ materially from those expressed in the estimates made by third parties and by us. Trademarks in this presentation are the
property of their respective owners and used for informational and education purposes only. 2
Our Mission: To Become a Leading Immunology Company Underpinned by
Strong Drug Discovery and Development Capabilities With Three, Differentiated, Clinical-stage Candidates and a deep pipeline of preclinical programs that target immune-mediated and inflammatory disease indications Our Internally-discovered Small
Molecule Drugs allow us to own 100% commercial rights to our entire portfolio with long patent lives for all product candidates Our Experienced Team And Our Internal R&D Engine continue to generate candidates with potential to address diseases
with high unmet need 3
Our Leadership Team Management Raju Mohan, PhD Martin Auster, MD Chris
Krueger, JD John Nuss, PhD William Sandborn, MD CHIEF EXECUTIVE OFFICER, CHIEF FINANCIAL OFFICER CHIEF BUSINESS OFFICER CHIEF SCIENTIFIC OFFICER PRESIDENT, CHIEF MEDICAL OFFICER FOUNDER Board Of Directors Sheila Gujrathi, MD Jigar Choksey Richard
Gaster, MD, PhD Raju Mohan, PhD EXECUTIVE CHAIR, VENTYX PRINCIPAL, THIRD POINT MANAGING PARTNER, VENBIO CHIEF EXECUTIVE OFFICER, VENTYX Aaron Royston, MD Somu Subramaniam William White MANAGING PARTNER, VENBIO MANAGING PARTNER, NEW SCIENCE CHIEF
FINANCIAL OFFICER, AKERO VENTURES THERAPEUTICS 4
Broad Pipeline of Candidates With Multiple Near-Term Catalysts
Addressing Established Inflammatory and Immunology Markets with a Wholly Owned Product Portfolio Target Program Preclinical Phase 1 Phase 2 Phase 3 Next Anticipated Milestones Initiate Phase 2 trials Q4 2022 TYK2 VTX958 Psoriasis, psoriatic
arthritis, Crohn's disease Report topline Phase 2 data 2023 S1P1R VTX002 Ulcerative Colitis NLRP3 Initiate Phase 2 trial in CAPS Q1 2023 VTX2735 Peripheral CAPS, other potential indications include CV, dermatologic and rheumatologic diseases
File IND Q1 2023 NLRP3 VTX3232 CNS-penetrant Initiate Phase 1 trial Q1 2023 Neuroinflammatory diseases Cash, cash equivalents and marketable securities of $412.4M as of September 30, 2022 expected to fund operations into 2025 5
Pipeline Targeting Large Well-Established Markets Indication* Patients
In The U.S. Global Drug Revenue* (2020) Target Population Psoriasis 25-30% ~8M ~$20B Dermatology Moderate-to-severe Crohn's disease 30-40% ~700K ~$13B IBD Moderate-to-severe Ulcerative colitis 30-40% ~1M ~$7B IBD Moderate-to-severe Psoriatic
arthritis 40-60% ~1M ~$4B Rheumatology Moderate-to-severe SLE Up to 500K ~$1B Rheumatology Sources: Evaluate Pharma, Company Estimates, Wall Street Research *Global drug revenue refers to the total market across all severity levels Notes: SLE =
systemic lupus erythematosus; *Group of indications based on current mid/late-stage trials for BMS's allosteric TYK2 inhibitor deucravacitinib; global commercial sales totaled $10.65B for biologics targeting IL-12/23 and IL-23 in 2020
ORALLY BIOAVAILABLE selective allosteric inhibitor of TYK2
VTX958: Orally Bioavailable, Selective Allosteric Inhibitor of TYK2
Clinically Validated Potential Best-in-Class Large Addressable Target Drug Markets Established clinical efficacy in IBD, Selective allosteric TYK2 inhibitor Multiple autoimmune disorders in psoriasis and psoriatic arthritis
with dermatology, IBD, renal and TYK2 functional selectivity may biologics targeting IL-12 and IL-23* rheumatology total ~$48B** in differentiate clinical profile vs. less 2020 WW sales Allosteric TYK2 inhibitors target selective
TYK2 inhibitors common pathways High unmet need for safe and Positive Phase 1 data: effective oral agents in markets TYK2 inhibition is clinically - Broad therapeutic window dominated by injectable biologics validated
in psoriasis, psoriatic - Excellent safety profile arthritis and SLE - Class-leading target coverage First allosteric TYK2 inhibitor FDA- may position VTX958 for success approved Sept. 9, 2022 -- no boxed warning differentiates
across multiple indications TYK2i from JAKi therapeutics *Includes approved drugs Stelara (JNJ), Tremfya (JNJ), Skyrizi (ABBV), Ilumya (Sun Pharma) and others in late-stage development (mirikizumab (LLY), brazikumab (AZN)
**Source: Positive Phase 3 efficacy results reported for deucravacitinib in psoriasis at AAD April 2021; positive Phase 2 efficacy results reported for psoriatic arthritis at ACR October 2020 and positive Phase 2 efficacy results reported for SLE at
EULAR meeting June 2022 Source: EvaluatePharma 2020 indication sales estimates 8
VTX958 Binds Selectively to the TYK2 Allosteric (JH2) Domain Key Players
in JAK/TYK2 Inhibited Active Inactive IL-12, IL-23, IFN Family Signaling Features of VTX958 JH2 Allosteric Domain JH2 Allosteric Inhibition Much less conserved amongst the JAK family Selectivity for TYK2 JH2 vs. with structurally distinct JAK1
JH2 domain (>4,000 X) binding pockets No binding to JAK2/3 JH2 JH1 Kinase Domain domains Highly conserved within JAK family; inhibitors No binding to TYK2 kinase JH2 targeting the kinase VTX958 JH1 and domain have poor JH1 selectivity No kinase
enzyme inhibition of any JAK family member TYK2 ATP Binding to JH1 allows phosphorylation of substrates Selective TYK2 Inhibitor Targeting the allosteric domain of TYK2 affords inhibitors with selectivity against other JAK isoforms
May Avoid Potential Safety Risks of JAK1/2/3 Inhibition 9
VTX958 is Highly Selective for TYK2 JH2 Domain vs. Deucravacitinib
Inhibits TYK2 Pathways (IL-12, IL-23, IFN ) while Avoiding the JAK1/2/3 Pathways TYK2 JH2 domain Structural Rationale for VTX958 Selectivity: Productive interaction for both VTX958 and deucravacitinib with valine residue in TYK2 JH2
domain VTX958 has a steric clash with the isoleucine residue (IIe) in the JAK1 JH2 domain - deucravacitinib does not Key determinant of the high TYK2 selectivity of VTX958 JAK1 JH2 domain JH2 Binding (K ) Deucravacitinib VTX958
d TYK2 0.009 nM 0.058 nM JAK1 0.43 nM 240 nM Fold Selectivity for 48 >4,000 TYK2 vs. JAK1 Source: Ventyx internal data 10
VTX958 Selectively Inhibits IL-12, IL-23 and IFN Signaling VTX958
Has No Measurable Inhibition VTX958 Potently Inhibits TYK2 Pathways of JAK1-Mediated Pathways Selective and potent inhibition of IL-12/23 and IFN Lack of inhibition of IL-6, IL-10, IL-22 and other protective axis allows targeting pathways
driving immune- cytokines may avoid potential adverse events associated mediated diseases with less selective inhibitors PROINFLAMMATORY INNATE & TH1/TH17 CYTOKINES PLEIOTROPIC CYTOKINES WITH PROTECTIVE FUNCTIONS Psoriasis Patient PBMC IL-12
IL-23 IFN IL-22 IL-10 IFN IL-4 IL-6 DRUG DRUG IC (nM) IC (nM) IC (nM) IC (nM) IC (nM) IC (nM) IC (nM) IC (nM) 50 50 50 50 50 50 50 50 VTX958 VTX958 35 5 12 >10,000 >10,000 >10,000 >10,000 >10,000 deucravacitinib 114 20 350
249 464 deucravacitinib 10 10 5 Potent activity against IL-23, a key cytokine implicated in psoriasis and other indications KEY TAKEAWAYS Broad therapeutic window with VTX958 may allow for higher exposures in Phase 2/Phase 3 studies
Source: Ventyx internal data; assays conducted in peripheral blood mononuclear cells (PBMC) 11
Summary of VTX958 Phase 1 Results Safety, Exposure and Target Coverage
VTX958 well tolerated across all SAD and MAD cohorts VTX958 exhibits class-leading Achieved TYK2 IC coverage for up to 24 hours with no dose-limiting toxicities 90 TYK2 IC coverage* 90 Robust, dose-dependent Supports hypothesis that
greater pathway inhibition may enable differentiated pharmacodynamic activity in efficacy in clinic ex vivo and in vivo assays *TYK2 IC coverage implies suppression of IL-12, IL-23 and IFN pathways 90 12
VTX958 Phase 1 Day 10 (Steady State) MAD Results Exposure and Target
Coverage Across All Cohorts Target Coverage* (hours) KEY TAKEAWAYS IFN IL-12 IL-23 MAD Dose Safely achieved class-leading IC IC IC IC IC IC 90 50 90 50 90 50 TYK2 IC coverage 90 50 mg BID 0 505 07 IC coverage up to 24 hours 90
for IL-12, IL-23 and IFN 250 mg QD 4 9 4 9 6 10 Exposures achieved may 500 mg QD 6 14 6 14 7 16 approach biologic-like suppression of IL-12/23 175 mg BID 16 24 16 24 17 24 pathways 350 mg BID 24 24 24 24 24 24 *Exposures used for
target coverage calculations: IL-12 hWB IC = 865 ng/mL; IC = 130 ng/mL; IFN hWB IC = 584 ng/mL; IC = 73 ng/mL 90 50 90 50 IL-12 IC and IC values used for IL-23 IC and IC calibration (hWB assay not available for IL-23) 50 90 50
90 IL-12 and IL-23 share TYK2-specific heterodimer IL-12R 1 13
VTX958 Phase 1 MAD Pre-IFN Challenge Safety Assessment* VTX958
Placebo 50mg BID 250mg QD 175mg BID 500mg QD 350mg BID All cohorts TEAEs (n=10) (n=6) (n=6) (n=6) (n=6) (n=6) (n=30) Headache 1 (10.0%) - 2 (33.3%) 2 (33.3%) 1 (16.7%) 1 (16.7%) 6 (20.0%) @ Faeces soft 1 (10.0%) 1 (16.7%) 2 (16.7%) 1 (16.7%) - 1
(16.7%) 4 (13.3%) # Rash papular - - 1 (16.7%) - - 2 (33.3%) 3 (10.0%) Dry mouth - - - - 1 (16.7%) 1 (16.7%) 2 (6.7%) Abdominal pain - 2 (33.3%) - 1 (16.7%) - - 3 (10.0%) ALT, AST, GGT increase - - - - - 1 (16.7%) 1 (3.3%)
All TEAEs (Treatment Emergent Adverse Events) reported in 2 or more subjects receiving VTX958 prior to IFN Challenge on day 13 and single subject AEs of interest. IFN challenge not performed in cohort 5 (350 mg BID), AEs for all 14 days
of treatment are presented for Cohort 5. @ Both AEs in a single subject # Single skin papule on lower right cheek judged not drug related; mild; resolved with continued VTX958 dosing Two subjects in cohort 5 (350 mg BID) experienced mild
skin papules judged not drug related one subject with mild face papules that resolved with continued VTX958 dosing one subject with mild face/trunk papules that improved with continued VTX958 dosing One subject in cohort 5 (350 mg BID)
experienced increase in ALT, AST, and GGT, classified as mild; overlapped with COVID diagnosis 14
VTX958 Phase 1 MAD Results: Selected Laboratory Data No significant
effects on hematological parameters, lipids, CPK laboratory values Hemoglobin Neutrophils CPK 250 200 150 100 50 0 DAY 1 DAY 2 DAY 5 DAY 7 DAY 10 Platelets Lymphocytes Cholesterol 15 Hemoglobin (g/L) Lymphocytes (10^9/L) (Mean SD) (Mean
SD) Platelets (10^9/L) Neutrophils (10^9/L) (Mean SD) (Mean SD)
VTX958 Phase 1 MAD Results Robust Dose-Dependent Pharmacodynamic
Effects Complete suppression of IL-12 signaling Robust inhibition of TYK2-responsive genes CXCL10, ISG20, IFI27 Dose-dependent inhibition of IFN at all time-points Genes are direct downstream targets of IFN and display
diverse in response to IL-12/IL-18 dual stimulation onset, amplitude and resolution kinetics Implies complete suppression of IL-23 signaling Potent exposure-PD activity on all three genes IL-12 and IL-23 share TYK2-specific
heterodimer IL-12R 1 Response is dose-related through all cohorts tested Ex Vivo Ex Vivo IFN response IFN response (ELISA) to (ELISA) to IIL-12/IL-18 dual L-12/IL-18 dual stimulation stimulation In Vivo IFN challenge
- Impact on TYK2-mediated genes (% Inhibition* 175 mg BID) Time post- 4h 6h 8h 12h 16h 24h challenge CXCL10 97 82 42 95 95 63 >90% inhibition ISG20 80 69 54 79 101 39 IFI27 78 68 62 60 71 84 BL= baseline *% inhibition shown as placebo
adjusted geometric mean *Geometric mean 16
Published TYK2 Target Coverage Data Opportunity for VTX958 to
Differentiate with Improved Therapeutic Window Deucravacitinib (BMS) 6 mg & 12 mg QD Target Coverage Deucravacitinib (BMS) 6 mg & 12 mg QD Target Coverage First-generation allosteric TYK2 inhibitor exposures are limited by toxicities 150
Deucravacitinib 6mg QD (PsO dose) IC 90 achieves IC coverage for ~9 hours (does 50 not reach IC ) 90 100 12 mg QD Skin toxicities (acne, rash) emerge consistently at higher exposures 6 mg QD Fuller pathway inhibition (improved 50
therapeutic window) expected to drive differentiation IC Greater coverage of TYK2 IC , IC may 50 50 90 drive improved efficacy 0 Achievement of durable IC coverage may 0 6 12 18 24 90 be necessary to achieve efficacy in IBD Time
post-dose (hours) PK data modeled and graph adapted from Chimalakonda et al., Dermatol. Ther. 2021 Deucravacitinib TYK2 IC of 14 ng/mL from Catlatt et al. EULAR 2017 50 IC values generated assuming a Hill slope of 1. ss= steady state 90 17 Derived
Plasma Concentrations, ss (ng/mL)
Deucravacitinib - Skin AEs and Target Coverage Deucravacitinib VTX958
Phase 1 Data Establish Study Skin AE 3 mg BID 6 mg QD 6 mg BID 12 mg QD 12 mg BID Total Differentiation vs. Deucravacitinib P1 MAD HV Any skin related AEs 33% 56% 78% 42% Deucravacitinib elicits dose- P2 PsO Acne 2% 4% 9% dependent and
potentially dose- Pruritis 2% 7% 5% limiting skin toxicities P3 PsO Acne 2% Folliculitis 2% Skin findings observed with high P2 PsA Acne 3% 2% frequency at exposures > 6 mg Acneiform dermatitis 3% 3% QD (~9h TYK2 IC coverage) 50 Rash 4%
6% P2 Lupus Acne 3% 9% 8% VTX958 demonstrates potential Rash 2% 3% 8% best-in-class therapeutic window Any skin related AEs 17% 34% 34% - Achieved high TYK2 IC 90 P2 UC Acne 9% coverage without frequent Rash 12% skin AEs TYK2 IC : ~9 h
50 TYK2 IC : ~18 h 50 TYK2 IC : ~0 h 90 TYK2 IC : ~0 h 90 *Deucravacitinib AE data compiled from respective publications and/or company data releases Deucravacitinib Phase 1 MAD dose ranged up to 12mg BID; trial had 7 discontinuations in
deucravacitinib arms (8.4%) related to AEs (4 d/c associated with skin toxicities) TYK2 target coverage sourced from Chimalakonda et al., 2021 represents IL-12-stimulated IFN production hWB assay 18
Acne, Folliculitis and Rash are not On-Target Effects of IFN or
IL12/23 Inhibition Drug Mechanism of Acne Folliculitis Rash inhibition Anifrolumab (Saphnelo) IFN < 2% < 2% < 2% Ustekinumab (Stelara) IL12/23 < 1% < 1% < 1% Guselkumab (Tremfya) Anti-IL23 < 1% < 1% < 1% Risankizumab
(Skyrizi) Anti-IL23 < 1% < 1% < 1% Source: Prescribing information for each approved drug. 19
VTX958 vs. Competitor Allosteric TYK2 Inhibitors Comparison of Phase 1