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statements regarding: the anticipated timing of enrollment of clinical trials for Ventyx's product candidates; the expectation that the Phase 2 clinical trial for VTX002, along with an additional Phase 3 trial, may serve as the first of two
pivotal trials required for registration; the potential of Ventyx's product candidates to address a broad range of immune-mediated diseases; the potential of CNS-penetrant NLRP3 inhibitors to treat Alzheimer's disease, Parkinson's
disease, amyotrophic lateral sclerosis and multiple sclerosis; plans to advance Ventyx's product candidates; and the expected timeframe for funding Ventyx's operating plan with current cash, cash equivalents and marketable securities.
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
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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
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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. PAGE 2
COMPANY VTX958 PHASE 1 VTX002 PHASE 2 READY VTX2735 PHASE 1 CNS NLRP3
PRECLINICAL SUMMARY MILESTONES & HIGHLIGHTS PAGE 3
Our Leadership Team Raju Mohan, PhD CHIEF EXECUTIVE OFFICER, FOUNDER
Sheila Gujrathi, MD Aaron Royston, MD EXECUTIVE CHAIR, VENTYX MANAGING PARTNER, VENBIO Jigar Choksey Martin Auster, MD Chris Krueger, JD Somu Subramaniam PRINCIPAL, THIRD POINT CHIEF FINANCIAL OFFICER CHIEF BUSINESS OFFICER MANAGING PARTNER, NEW
SCIENCE VENTURES Richard Gaster, MD, PhD MANAGING PARTNER, VENBIO William White CHIEF FINANCIAL OFFICER, John Nuss, PhD J rn Drappa, MD, PhD Raju Mohan, PhD AKERO THERAPEUTICS CHIEF SCIENTIFIC OFFICER CHIEF MEDICAL OFFICER CHIEF EXECUTIVE
OFFICER, VENTYX PAGE 4
Our Mission: To become a Leading Immunology Company continue to generate
candidates allow us to own 100% and a deep pipeline of preclinical with potential to address commercial rights to our entire programs that target immune- diseases with high unmet need portfolio with long patent lives for mediated and inflammatory
all product candidates disease indications PAGE 5
Broad Pipeline of Candidates With Multiple Near-Term Catalysts TARGET
PROGRAM PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NEXT ANTICIPATED MILESTONES Complete Phase 1 MAD H1 2022 TYK2 VTX958 Initiate Phase 2 POC trial(s) H2 2022 Potential indications include psoriasis, psoriatic arthritis, Crohn's disease and others
Initiate Phase 2 trial Q4 2021 S1P1R VTX002 Report topline Phase 2 data 2023 Ulcerative Colitis Complete Phase 1 H1 2022 NLRP3 VTX2735 Peripheral Initiate Phase 2 POC trial(s) H2 2022 Potential indications include cardiovascular, hepatic, renal, and
rheumatologic diseases Select lead candidate Q4 2021 NLRP3 Discovery CNS-penetrant File IND H2 2022 Neuroinflammatory diseases PAGE 6
COMPANY TEAM, INVESTORS, & PIPELINE VTX958 VTX002 PHASE 2 READY
VTX2735 PHASE 1 Orally Bioavailable, CNS NLRP3 Selective Allosteric PRECLINICAL Inhibitor of TYK2 SUMMARY MILESTONES & HIGHLIGHTS PAGE 7
VTX958 Program Summary Multiple autoimmune disorders
Selective, allosteric TYK2 inhibitor Well established clinical efficacy in dermatology, IBD, renal and in psoriasis, IBD and psoriatic TYK2 functional selectivity can rheumatology total $45B WW arthritis with biologics targeting
potentially differentiate clinical IL-12/IL-23 and IL-23* pathways profile vs. less selective TYK2 inhibitors These pathways also the target of allosteric TYK2 inhibitors Phase 3 PoC in psoriasis has been demonstrated** by BMS'
allosteric TYK2 inhibitor deucravacitinib Deucravacitinib in Phase 2/3 for Crohn's disease, psoriatic arthritis, lupus Includes approved drugs Stelara (JNJ), Tremfya (JNJ), Skyrizi (ABBV), Ilumya (Sun Pharma) and
others in late-stage development (mirikizumab (LLY), brazikumab (AZN) **Deucravacitinib efficacy reported on 16-week primary endpoint of PASI-75 (75% reduction of psoriasis affected area and severity) at AAD 21; p<0.0001 vs placebo and
Otezla in POETYK-1; p=0.0003 vs. Otezla in POETYK-2; See slide 14 for more detail on $45B worldwide market PAGE 8
Allosteric Inhibitor VTX958 Binds Selectively to the TYK2 JH2 Domain
IL-12, Inhibited Active Inactive IL-23, IFNa Selectivity for TYK2 JH2 vs. JAK1 JH2 FERM/SH2 Receptor interaction domain (>4,000 X) JH2 Allosteric Domain Much less conserved amongst the No binding to JAK2/3 JAK family with structurally distinct
JH2 domains binding pockets JH2 JH1 Kinase Domain No binding to TYK2 VTX958 Highly conserved and kinase JH1 and JH1 inhibitors targeting the kinase domain have poor selectivity TYK2 No kinase enzyme ATP Binding to JH1 allows inhibition of any JAK
phosphorylation of substrates family member Targeting the JH2 (allosteric) domain of TYK2 affords TYK2 inhibitors with selectivity against other JAK isoforms PAGE 9
VTX958 More Selective than Deucravacitinib for TYK2 JH2 Domain IL-2,
IL-4 IL-10,IL-22 IFN / IL-12/23 IFN IL-13, IL-15 IL-6 DEUCRAVACITINIB TYK2-JH2 Binding K 0.009 nM 0.058 nM d JAK1 TYK2 JAK1 TYK2 JAK1 JAK1 JAK1-JH2 Binding K 0.43 nM 240 nM d other JAK JAK2 JAK3 JAK2 Selectivity (fold) 48 >4,000
JAK1 dependent signaling pathways TYK2 essential signaling pathways Source: Ventyx internal data PAGE 10
VTX958 Selectively Targets IL-12, IL-23 and IFNa Proinflammatory Innate
& Th1/Th17 Cytokines Psoriasis Patient PBMC Selective and potent IL-23 IFN IL-12 Drug Potent activity IC (nM) IC (nM) 50 IC (nM) 50 50 inhibition of IL-12/23 and against IL-23, a Type I interferon axis VTX958 35 5 12 key cytokine allows
targeting pathways implicated in deucravacitinib 10 10 5 driving immune-mediated psoriasis and other diseases indications Broad therapeutic Pleiotropic Cytokines with Protective Functions window with VTX958 may allow IL-22 IL-10 IFN IL-4 IL-6
Drug for higher IC (nM) IC (nM) IC (nM) IC (nM) IC (nM) 50 50 50 50 50 exposures in Lack of inhibition of IL-6, VTX958 >10,000 >10,000 >10,000 >10,000 >10,000 Phase 2/Phase 3 IL-10 and other protective studies cytokines may avoid
deucravacitinib 114 20 350 249 464 potential AEs associated with less selective inhibitors Source: Ventyx internal data; conducted in peripheral blood mononuclear cells (PBMC) PAGE 11
VTX958 Phase 1 SAD Results Support Clinical Advancement Well-tolerated
across all No dose-saturation observed; PK Dose-dependent VTX958-mediated effect on cohorts; all AEs observed and absorption profiles suggest continued TYK2 signaling observed in both in vivo were mild and not dose- or absorption throughout GI tract
gene expression studies and ex vivo time-of-dose dependent stimulation assays NOTE: SAD = single ascending dose; AE= adverse event; dose-related exposures are observed at all doses PAGE 12
VTX958 Clinical Development Plan Phase 1 MAD Phase 2 PoC All 7
cohorts Explore safety and completed exposure data on Phase 2 PoC Phase 2 trials planned in repeat dosing Safety and additional indications Initial Phase 2 trial in exposure data allow (psoriatic arthritis, Crohn's
Elucidate PD profile moderate-to-severe disease and others) exploration of high with multiple dose psoriasis patients exposure multiples exposure across VTX958's selectivity may in MAD trial TYK2 inhibition is a therapeutic range Phase 1 MAD
allow for differentiation in de-risked mechanism for Complete Trial multiple indications Select Phase 2 doses treatment of psoriasis DOSING COMPLETE INITATEDQ4 DO 2 S 0 IN 21 G Q4 2021 H1 2022 H2 2022 H2 2022 CMC & Toxicology Planning
Chronic toxicology studies in process to support Phase 2/3 trials Additional Phase 2 trials Solid oral dose form developed for Phase 2/3 trials NOTE: SAD = single ascending dose; MAD = multiple ascending dose; PoC = proof-of-concept
Commercial Potential in 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
Psoriasis and Psoriatic Arthritis ~1M patients in U.S.
~8M patients in U.S. Significant share shift in recent years Up to ~40-60% are moderate-to-severe 25-30% are moderate-to-severe from anti-TNF agents to newer Total treated U.S. moderate-severe U.S. biologic
penetration ~15-20% biologics (anti-IL-23, IL-12/23 and population ~500k* Total treated U.S. moderate-severe population anti-IL-17s antibodies) Global revenue of PsA drugs ~$4B in ~1.2m* Global revenue of psoriasis drugs
~$20B in 2020 2020 Despite limitations, Otezla had $2.2B in 2020 sales and is the only major Other, Skyrizi oral player in these markets 12% (ABBV), 8% TYK2 de-risked in both indications by Cosentyx (NVS), 15% deucravacitinib Humira
(ABBV), Psoriasis: Phase 3 trial 6mg QD 17% dose was statistically superior vs. Otezla* PsA Phase 2 data showed stat. Taltz (LLY), significant ACR20 and ACR50 Stelara (JNJ), 7% scores vs pbo^; now in Phase 3 24% trials at 6mg QD
dosing Otezla (AMGN), 9% Tremfya (JNJ), 7% Sources: Evaluate Pharma, Company Estimates, Wall Street Research; *BMS AAD 2021 Presentation; PsA=psoriatic arthritis; *BMS deucravacitinib: 54-59% responses on PASI75 at 16 weeks achieved statistically
significant results vs. apremilast control ^6/12mg ACR20: 53/63% vs 32%; ACR50: 24/33% vs 11% PAGE 15
Crohn's Disease ~700k+ Crohn's disease patients in
U.S. ~$13B market dominated by 30-40+% are moderate-to-severe U.S. biologic penetration ~35-40% parenteral biologic therapies Global revenue of Crohn's disease drugs ~$13B in 2020 Share trends have
favored Stelara (anti-IL-12/23) with more selective anti-IL-23 biologics (i.e. Skyrizi) producing positive Phase 3 data Dosing of IL-23 targeting biologics in CD may be as great as 3-4x dosing in dermatology indications Biologics
targeting anti-IL12/23 and anti-IL23 provide rationale for TYK2 inhibitor development; higher selectivity may yield wider therapeutic index, potentially supporting differentiation Sources: Evaluate Pharma, Company estimates, Wall Street research,
BMS AAD 2021 Presentation; Skyrizi label dosing for psoriasis/PsA vs. Phase 3 Crohn's dosing regimen PAGE 16 Confidential
COMPANY TEAM, INVESTORS, & PIPELINE VTX958 PHASE 1 VTX002 VTX2735
PHASE 1 Peripherally Restricted S1P1R CNS NLRP3 Modulator with Potential for Treatment PRECLINICAL of Ulcerative Colitis SUMMARY MILESTONES & HIGHLIGHTS PAGE 17
VTX002 Program Summary Selective S1P1R modulator S1P1R
modulators approved for Ulcerative colitis is lead MS and UC with clinical trials indication totaling up to $7B in Differentiated on key parameters ongoing in other indications worldwide revenue Demonstrated pharmacodynamic
BMS' ozanimod approved for activity in Phase 1 trial UC in May 2021 Pursuing clinical development plan in both treatment-na ve and biologic-experienced patients PAGE 18
VTX002 Differentiates on Multiple Key Parameters vs. Competitors No CYP
inhibition; no food effect; favorable No SAEs, elevated LFTs, abnormal profile for patients with co-morbidities Sustained lymphocyte reduction up to 65% PFTs or macular edema across multiple doses in MAD trial Very low CNS penetration; not a
Potential to avoid first-dose cardiac repurposed MS drug; potential to No long-acting circulating metabolites monitoring in label avoid macular edema Optimal half life (t~20h) Notes: SAE=significant adverse event; MAD=multiple ascending dose PAGE
Phase 1 MAD Results: Dose-Dependent Exposure and Lymphocyte Reduction 0
-20 -40 -60 ****p< 0.0001 **** **** **** **** **** **** **** **** -80 Placebo 2 mg 10 mg 20 mg 35 mg 45 mg T of ~20 hours 1/2 Demonstrated consistent, sustained reduction of lymphocytes up to 65% across multiple dose groups
Dose-proportionate exposure after single and multiple doses of VTX002 with steady-state reached after 4 to 7 days of target-dose exposure Source: NEJM (2016), Gastroenterology (2020) *Ph2 UC ALC reduction from baseline: 1mg ozanimod (49%),
2mg etrasimod (40%) PAGE 20 Placebo 2 mg 10 mg 20 mg 35 mg 45 mg Absolute Lymphocyte Count % Change from Baseline (Mean SD)
Phase 2 Trial in Moderate-to-Severe Ulcerative Colitis Patients N=180;
1:1:1 Powered for primary endpoint of clinical 13-Week Induction Treatment 39-Week, Open-Label Extension Treatment (7-day titration + 12 weeks placebo/target dose) 7-day titration + 38 weeks 60 mg dose remission 39 weeks Yes VTX002 60 mg VTX002 60
mg Trial may serve as the Week 13 first of two pivotal trials VTX002 30 mg R 13 weeks Week 26 26 weeks required for registration Yes R VTX002 60 mg VTX002 60 mg Placebo No 13 weeks Week 1 Week 52 No Discontinuation Week 13 Primary Endpoint Clinical
Remission Week 26 Symptomatic Response Note: Phase 2 tablet doses of 30mg and 60mg provide comparable VTX002 exposure as Phase 1 suspension doses of 20mg and 40mg, respectively PAGE 21
Underpenetrated Market for Biologic Refractory Patients
Existing agents leave room for new treatments ~1M UC PATIENTS Novel oral agents may expand penetrance of treated moderate-to- 300K+ severe UC population MODERATE-TO-SEVERE UC PATIENTS beyond current ~25- 30% ~100K S1P well positioned
to BIOLOGIC-TREATED PATIENTS emerge as leading oral TARGET POPULATION therapeutic class based on its attractive class Biologic-experienced patients >50K efficacy/safety profile NOT IN REMISSION PAGE 22
COMPANY TEAM, INVESTORS, & PIPELINE VTX958 PHASE 1 VTX002 PHASE 2
READY VTX2735 CNS NLRP3 Selective NLRP3 Inflammasome Inhibitors for Systemic and CNS Indications SUMMARY MILESTONES & HIGHLIGHTS PAGE 23