Slides
Page 1
Creating Transformative Medicines to Improve Patients’ Lives July 24, 2025
Page 2
2 Forward-Looking Statements and Disclaimers This presentation includes certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements regarding Janux Therapeutics, Inc. (the “Company”). These forward-looking statements include, but are not limited to, those regarding the Company’s ability to bring new treatments to patients in need, the progress and expected timing of the Company’s drug development programs, and clinical development plans and timelines and estimates regarding the Company’s expenses and capital requirements. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that the Company may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings and applications, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Also, interim results of a clinical trial are not necessarily indicative of final results and one or more of the clinical outcomes may materially change following more comprehensive reviews of the data, as patient enrollment continues, and as more patient data become available, including the risk that unconfirmed responses may not ultimately result in confirmed responses to treatment after follow-up evaluations. In light of these risks, uncertainties, contingencies and assumptions, the events or circumstances referred to in the forward-looking statements may not occur. For a further list and description of the risks and uncertainties that the Company faces, please refer to the Company’s periodic and other filings with the Securities and Exchange Commission, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and the Company assumes no obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. This presentation concerns therapeutic product candidates that are in preclinical and clinical development and which have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. Certain data in this presentation are based on cross-study comparisons and are not based on any head-to-head clinical trials. Cross-study comparisons are inherently limited and may suggest misleading similarities or differences. Actual results may differ from these comparisons. Differences exist between study or trial designs and subject characteristics, and caution should be exercised when comparing data across studies.
Page 3
3 Janux – multiple near-term high value opportunities in cancer and I&I Clinical Programs Development Pipeline Cash Position *As of March 31, 2025, includes cash, cash equivalents and short-term investments • JANX007: PSMAxCD3-TRACTr undergoing P1b dose expansion trials in mCRPC • Position JANX007 to move into early lines of mCRPC therapy • JANX008: EGFRxCD3-TRACTr undergoing clinical P1a evaluation in multiple solid tumor settings • PSMAxCD28-TRACIr: designed to enhance T cell activation and durability of JANX007 • IND anticipated in 1H2026 • TROP2xCD3-TRACTr: TRACTr platform provides access to previously intractable TCE target • IND-enabling activities planned in 2H2025 • CD19-ARM: novel bispecific with potential in autoimmune disease and heme-onc • First patient treated in HNV trial planned in 1H2026 • Robust cash position of $1.01 billion* as of March 2025 • Runway through JANX007 interim pivotal data, JANX008 P1b data and human proof-of-concept data on TROP2-TRACTr, PSMAxCD28 TRACIr and CD19-ARM
Page 4
4 Summary of new programs PSMAxCD28-TRACIr Program TROP2-TRACTr Program CD19-ARM Program • Combination with JANX007 to further differentiate depth and durability of patient responses • CD28-based TRACIr platform designed to enhance T cell activation and durability of CD3-based TRACTr platform • TRACTr and TRACIr platforms built on same technology with same tumor-activation and PK design features • Builds upon learnings from JANX007 and JANX008 clinical programs • TRACTr technology unlocks access to potential high-value TCE target • Provides broad solid tumor indication expansion to Janux clinical portfolio • Builds upon Janux TCE expertise to redesign bispecific T-cell engagers • Differentiated non-clinical profile provides best-in-class opportunity • Extends Janux pipeline into autoimmune disease
Page 5
5 Janux pipeline Target Indications Discovery IND-Enabling Phase 1 Phase 2 Phase 3 Wholly owned TRACTr Programs JANX007 PSMA x CD3 mCRPC JANX008 EGFR x CD3 EGFR+ solid tumors TROP2-TRACTr TROP2 x CD3 TROP2+ solid tumors Wholly owned TRACIr Program PSMA-TRACIr PSMA x CD28 mCRPC Wholly owned ARM Program CD19-ARM CD19 AID Partnered Programs Merck Two Undisclosed Undisclosed Program Progress Not Disclosed
Page 6
6 Janux Tumor Activated T-Cell Engager (TRACTr) platform design principles Each program is designed as a potent T-cell engager with reduced toxicity Emerging JANX007 clinical data demonstrates TRACTr platform can potentially improve both safety and efficacy compared to contemporary TCEs TRACTr Design Healthy Tissue Tumor Tissue Healthy Tissue Masks block activity against healthy tissues to reduce CRS and on-target, healthy tissue toxicity Tumor specific activation to maximize anti-tumor immune response TCE is rapidly cleared from healthy tissue to limit systemic toxicity
Page 7
Tumor Activated Immunomodulator (TRACIr) Platform Introduction
Page 8
8 TRACIr platform designed to enhance activity and durability of TRACTr platform Combination with JANX007 to further differentiate depth and durability of patient responses Janux raised the bar with JANX007† Best-in-treatment potential in prostate cancer Addition of PSMA-TRACIr strengthens Janux’s prostate cancer franchise CD28 binding domain PSMA binding domain Half-life extension Albumin binding domain PSMA-TRACIr • Enhance a potentially best-in-treatment asset, JANX007, with CD28 co-stimulation • Decrease T-cell exhaustion to increase durability • Deeper longer clinical responses †Data disclosed from JANX007 Dec 2024 public update and May 2025 public update with respect to rPFS. *includes confirmed and unconfirmed responses Median Tx line rPFS (mo) median % rPFS 6-month ORR* Best PSA decline ≥ PSA50 at 12wks ≥ PSA90 at 12wks 5L 7.5-7.9 65-78% Janux aims to raise the bar again Combining PSMA-TRACTr with PSMA-TRACIr 50% 75% 50%PSA50: PSA90: 100% 63%
Page 9
9 PSMA is an ideal target to evaluate TRACIr platform Opportunity for rapid proof of concept What we know in prostate cancer 1 2 3 JANX007 clinical results validate* tumor activated platform in mCRPC mCRPC is PSMA-TRACTr* and PSMAxCD28-costimulation† responsive Predictable dose dependent clinical activity* makes JANX007 ideal combination agent PSMA-TRACTr + PSMA-TRACIr rationale Note: “Validate” refers to early clinical validation of TRACTr platform from JANX007 clinical data aligning with the platform design principles and expectations *(based on Dec-2024 and May-2025 program public updates). †Stein et al 2023 (REGN5678) PSMA-TRACIr built with the same technology and design principles as PSMA-TRACTr Janux mCRPC drug development expertise can be applied to generate rapid TRACIr platform proof of concept Enhanced activity and durability potential PSMA-TRACIr may further differentiate Janux therapies in the prostate cancer treatment landscape
Page 10
10 CD28-costimulation to potentially enhance duration of TRACTr mediated anti-tumor activity Combination designed to further improve T cell immune response against the tumor T cell activation Tumor cell Signal 1 Signal 2 CD3 CD28 PSMA Enhanced durability from TRACTr plus CD28-costimulation Complementary tumor activated platforms aim to safely enhance depth and duration of T cell anti-tumor response Signal-1 + Signal-2 PSMAxCD3 (TRACTr) + PSMAxCD28 (TRACIr) • Provides tumor recognition element to T cells (signal 1) leading to T cell activation • Signal 1 drives anti-tumor T cell response and tumor cell killing Activated TRACTr – Signal 1 Activated TRACIr – Signal 2 • Co-stimulation through PSMAxCD28 (signal 2) enhances T cell activation and expansion • Signal 2 increases durability of T cell driven anti-tumor response Activated TRACTr (unmasked) Activated TRACIr (unmasked) Benefit from signal 2 requires presence of signal 1
Page 11
11 Janux TRACTr + TRACIr complementary platforms with potential best-in-class safety and efficacy TRACTr and TRACIr combination approach Unique opportunity to differentiate from non-masked approaches Non-masked CD28 approaches limited by toxicity ‡Dorff 2024 (AMG160); *Stein 2023 (REGN5678); ‡Eaton 2023 ₶Calvo 2025 (SAR443216; NCT05013554) ESMO https://doi.org/10.1016/j.esmoop.2025.104199); Severe toxicity observed (≥Gr3 53% and 2 Gr5 AEs) Clinical activity of REGN5678 validates that CD28 co-stimulation can drive efficacy in prostate cancer TRACTr + TRACIr – Competitive differentiation Masked TAA x CD3 + Masked TAA x CD28 Flexible dosing and tunable timing for each molecule to optimize patient anti-tumor immune response Masks designed to reduce healthy tissue toxicity and CRS may be required based on clinical toxicity from non-masked assets (AMG160 ‡, REGN5678* , SAR443216₶) Potentially access higher doses, increase intra-tumoral drug concentrations, and elicit stronger efficacy designed to safely maximize strength and duration of anti-tumor T cell response No objective responses with DLTs of cardiac failure where Her2 is expressed ‡ and Gr4 transaminases PSMA x CD28 (REGN5678)* Her2 x CD3 x CD28 (SAR443216)₶ Trispecifics CD3 x TAA x CD28 limited by design Intramolecular stoichiometry constraints may not match what is required for optimal T cell activation CD3 and CD28 binding in trans could lead to T cell fratricide Dose and timing of CD3 and CD28 cannot be independently varied which may be required for best clinical outcomes DLT = dose limiting toxicity
Page 12
12 PSMA-TRACIr enhancement of T cell mediated tumor cell killing Masking designed to reduce CRS and healthy tissue toxicity CD28 co-stimulation enhances TCE activity PSMA-TRACIr designed to enhance PSMA-TRACTr in combination LNCaP tumor cell killing Control PSMA-TCI EC20 PSMA-TCE EC20 PSMA-TCE + 1nM PSMA-TCI Cleavage dependent functional activity PSMA-TCI lacks activity as a single agent but enhances tumor cell killing of PSMA-TCE in combination -1 0 1 2 3 4 5 6 0 20 40 60 80 100 PSMA-TRACIr or -TCI (Log pM) Tumor cell viability EC20 PSMA-TCE + PSMA-TCI EC20 PSMA-TCE + PSMA-TRACIr EC20 PSMA-TCE + PSMA-TRACIr +MMP9 LNCaP tumor cell killing PSMA-TCE = PSMAxCD3 PSMA-TCI = PSMAxCD28 PSMA-TRACIr exhibits large functional shift relative to non-masked PSMA-TCI PSMA-TRACIr = masked PSMAxCD28 0 20 40 60 80 100 120Tumor cell viability No stim No activity EC20 Full killing >7,000x
Page 13
13 Learnings from clinical TCE programs† Loss in T-cell function during dosing period and upon disease progression has been reported for multiple oncology clinical programs (Blinatumomab, teclistamab, and talquetamab) TRACIr extends duration of TRACTr mediated tumor killing CD28 co-stimulation prolongs T cell cytolytic function CD28 co-stimulation improves duration of T cell mediated cytolytic activity PSMAxCD3 PSMAxCD3 + PSMAxCD28 Single agent Combo throughout PSMA-TRACIr enhanced duration of the PSMA-TRACTr anti-tumor response highlights the opportunity to further differentiate a potentially best-in-treatment therapy in prostate cancer T cell durability assay Rechallenge with fresh tumor cells every ~5-7 days Monitor real time tumor cell killing T cells Prostate cancer cells Assay designed to drive rapid T cell exhaustion Non-clinical durability data supports plans to combine PSMA-TRACTr and PSMA-TRACIr in prostate cancer patients Single agent then combo PSMAxCD3 + PSMAxCD28 †Verkleij et al 2024; † Philipp et al 2022 0 10 20 30 40 50 0 50 100 150 200 300 400 500 10,000 Days Normalized LNCaP Tumor Density Tumor outgrowth after three treatments Full tumor cell killing maintained throughout Rescued tumor control upon addition of PSMAxCD28 Combo start
Page 14
14 PSMA-TRACIr profile in cynomolgus monkey Well tolerated as a single agent or in combination with PSMA-TRACTr Large safety window in NHPs Combination PSMA-TRACTr and PSMA-TRACIr exhibits large safety window above anticipated efficacious doses *Based on in vitro MABEL in combination with PSMA-TCE No adverse findings in cynos Non-masked PSMA-TCE Transient cytokine induction and elevation in liver enzymes PSMA-TRACTr Transient cytokine induction at high doses No adverse clinical signs or pathology changes PSMA-TRACTr + PSMA-TRACIr No enhancement of cytokine release, no adverse clinical signs, no observable healthy tissue toxicities 0 7 14 21 0.1 1 10 100 PSMA-TRACIr Plasma concentration (nM) 500 Projected Human Efficacious Dose* Days 1mg/kg IV PSMA-TRACIr Single agent TRACIr Active dose PSMA-TRACTr Single agent TRACTrCombination TRACTr + TRACIr 1mg/kg IV PSMA-TRACIr Active dose PSMA-TRACTr + -1 0 200 400 600 800 1000 0 1 2 3 4 5 6 7 pg/mL -1 0 200 400 600 800 1000 0 1 2 3 4 5 6 7 pg/mL -1 0 500 1000 1500 2000 2500 3000 0 1 2 3 4 5 6 7 pg/mL -1 0 200 400 600 800 1000 0 1 2 3 4 5 6 7 pg/mL Days IFNγ TNF IL-6 IL-2
Page 15
15 First patient treated with PSMA TRACIr in combination with JANX007 planned in 2H-2026 IND enabling studies in progress PSMA TRACTr expertise and experience expected to accelerate PSMA TRACIr proof of concept Phase 1 planned in 2H-2026 Prostate Cancer Disease progression Key Phase 1 Evaluations • PK, safety, and tolerability • PSA, RECIST, durability • TRACIr platform validation Non-clinical data supports flexible timing for PSMA-TRACIr dosing (contemporaneously or delayed relative to JANX007 1st dose) IND enabling studies • Non-clinical toxicology in NHP • In vitro pharmacology and immunotoxicity safety assessments • GMP manufacturing • IND anticipated in 1H-2026 PSMA-TRACTr Dosing PSMA-TRACIr Dosing Prior clinical experience guides JANX007 dosing IND in 1H-2026 • Dose regimen finding • T cell expansion and phenotype
Page 16
16 Best-in-treatment opportunity Janux positioning to strengthen its prostate cancer franchise Opportunity to raise the bar again in prostate cancer with a TRACTr + TRACIr combination PSMA-TRACIr comprises clinically validated design principles with a rapid path to clinical proof of concept • JANX007 exhibits predictable dose dependent clinical activity* • Enhancement in durability from CD28-costimulation demonstrated in non-clinical studies • Large safety window in NHP at combination exposures well above those anticipated to drive efficacy in humans Combination with potentially best-in-class JANX007 Rapid TRACIr development path Clinically validated design principles • Prostate cancer is a known PSMA-TRACTr and PSMAxCD28 responsive tumor type • Potentially stronger responses with prolonged durability • Reduced risk of CRS and healthy tissue toxicity by design PSMA-TRACIr For treatment of PSMA expressing solid tumors in combination with TRACTrs • JANX007 experience may facilitate accelerated clinical development to enable rapid TRACIr PoC • FPI planned in 2H-2026 T cell binding domain (CD28) Tumor binding domain (PSMA) Half-life extension Albumin binding domain Note: “Clinically validated” refers to early clinical validation of TRACTr platform from JANX007 clinical data aligning with the platform design principles and expectations *(based on Dec-2024 and May-2025 program public updates). FPI = First Patient In
Page 17
TROP2-TRACTr
Page 18
18 TROP2-TRACTr leverages clinically validated platform and target to access new tumor types High unmet need – Market Potential Target Selection Rationale – Strategic Focus Competitive Differentiation Leverage learnings from JANX007 and JANX008 clinical programs Accelerate TRACTr development where targeted agents have had clinical success Access new indications across Janux portfolio Designed for improved safety and efficacy vs. ADCs (73% Gr≥3 TEAEs for Trodelvy‡) Response potential across full spectrum of TROP2 expression densities (including low expression) Designed to enable higher doses, higher intratumoral levels of active drug, and stronger efficacy 1 2 3 TROP2+ tumors - 2L+ incidence USA & EU5₼ NSCLC 209K HR+ BC 60K HER2+ BC 25K TNBC 20K SCLC 19K OC 25K UC 14K CC 14K EC 8K ESCC 4K >400K treated patients annually Multi-billion-dollar market potential TRACTr platform unlocks opportunity for a potential first-in-class TROP2-TCE Expansion into a high value target opportunity via clinically validated TRACTr platform ‡Bardia 2024; ₼Competitive intelligence from company reports and publicly available epidemiology data including SEER.
Page 19
19 Cleavable linker TROP2-TCEs likely require tumor-activated approach Contemporary TCEs unable to access TROP2 target due to broad healthy tissue expression *Chen et al 2024 TROP2-PET imaging of healthy volunteers* TRACTr designed to reduce healthy tissue toxicityHealthy tissue expression limits contemporary TCEs CD3 binding domain TROP2 binding domain Activity restricted to TROP2+ TME Active wherever TROP2 is expressed TROP2-TRACTrTROP2-TCE CD3 binding domain TROP2 binding domain Albumin binding domain Cleavable linker CD3 mask TROP2 mask Lung cancer example TROP2-TRACTr designed to reduce CRS and healthy tissue toxicity limitations of conventional TCEs Broad TROP2 expression in skin, kidney, bladder, parotid, thyroid, salivary gland, liver, pancreas TROP2 expressed in overlapping healthy & tumor tissues Poses substantial dose limiting toxicity risk Masking to block target engagement and activity in healthy tissue Proteolytic cleavage to focus activation to TME Switch PK mechanism to enable rapid clearance of active drug once cleared from TME
Page 20
20 Optimized TROP2-TRACTr exhibits large activity multiples across tumor cell lines TROP2-TRACTr exhibits a large functional potency shift relative to non-masked TCE -3 -2 -1 0 1 2 3 4 5 0 20 40 60 80 100 120 Log [pM] Skin Cancer: A431 Lung Cancer: H292 600,000 TROP2/cell 225,000 TROP2/cell Janux TROP2-TRACTr offers an opportunity to treat many solid tumors with high unmet need TRACTr provides opportunity to treat tumors with a wide range of receptor densities Colon cancer: HCT116 15,000 TROP2/cell -3 -2 -1 0 1 2 3 4 5 0 20 40 60 80 100 120 Log [pM] Breast cancer: MDAMB231 -3 -2 -1 0 1 2 3 4 5 0 20 40 60 80 100 120 Log [pM] 35,000 TROP2/cell TROP2-TCE TROP2-TRACTr Protease cleaved TROP2-TRACTr -3 -2 -1 0 1 2 3 4 5 0 20 40 60 80 100 120 Log [pM] Target Cell Viability
Page 21
21 TROP2-TRACTr active at low TROP2 expression density levels Opportunity to treat patients across all levels of TROP2 expression TROP2-TRACTr is active in low TROP2 expression tumor model *Goldenberg et al 2015; †Meric-Bernstam et al 2025; ₼Okajima et al 2021 0 7 14 21 28 35 0 20 40 60 80 100 Days Percent Survival X 75mm3 X 144mm3 X: terminated due to GVHD; tumor volume at termination indicated TROP2-ADCs exhibit minimal activity in low TROP2 expression tumor models TROP2 H-score >100 required for response†,₼ TROP2 H-Score 100 200 300 0 Non- responders Responders Datroway† 4,000 3,000 2,000 1,000 0 0 4 7 11 14 18 21 Days Tumor volume (mm3) TROP2 H-score = 41 TNBC PDX MDAMB231 Days (25mg/kg) Trodelvy* % change tumor volume 0 7 14 21 28 0 250 500 750 1,000 1,250 1,500 1,750 Days Mean Tumor Volume (mm3) QD x 10 MDAMB231 Vehicle NC-TRACTr (1.5mg/kg) TCE (0.5mg/kg) TRACTr (1.5mg/kg) Stronger TROP2-TRACTr anti-tumor activity at low TROP2-expression density differentiates from ADCs Trodelvy and Datroway exhibit minimal activity in tumor models and patients with low TROP2 expression (below ADC activity threshold) TROP2-TRACTr demonstrates prolonged survival benefit Cleavage dependent TROP2-TRACTr activity
Page 22
22 TROP2 Expression (H-Score) % Patients Number Patients Treatment mPFS (mo) mOS (mo) ORR CR + PR VERY LOW < 50 13% 21 TPC Not reported Not reported 10% 0 20 SG 15% 3 LOW 0-130 25% 45 TPC 1.5 7.0 4% 2 35 SG 2.7 8.7 23% 8 MEDIUM 130-220 25% 33 TPC 2.8 8.8 15% 5 47 SG 4.8 13.4 28% 13 HIGH 220-275 25% 40 TPC 1.6 6.5 0% 0 39 SG 6.8 15.2 41% 16 VERY HIGH 275-300 25% 32 TPC 2.8 7.1 0% 0 47 SG 6.9 14.5 45% 21 Outcomes in TROP2-ADC treated TNBC patients deteriorate if tumor TROP2 expression is low TROP2-TRACTr aims to provide stronger benefit to patients with low TROP2 expression TROP2 expression impacts ADC clinical benefit in TNBC‡ ‡Bardia et al 2024 TROP2-ADC: Sacituzumab-govitecan (SG; Trodelvy) Treating physician’s choice (TPC) Reduced efficacy in 50% of TNBC patients (H-score ≤ 220) treated with TROP2-ADC‡ • TROP2-TRACTr in vivo anti-tumor activity requires less TROP2 expression than ADCs • Opportunity for TROP2-TRACTr to improve efficacy where ADCs are limited by reduced TROP2 target expression Opportunity for TROP2-TRACTr in patients with otherwise limited clinical response due to low TROP2 expression
Page 23
23 TROP2-TRACTr TROP2-TRACTr is well tolerated in NHP TRACTr reduced CRS and healthy tissue toxicity compared to non-masked TROP2-TCE Masking prevents toxicity in NHP TROP2-TRACTr large safety multiple Minimal cytokine release 0 2 4 6 8 10 12 14 0.001 0.01 0.1 1 10 100 Days post dose TROP2-TRACTr plasma concentration (nM) 0.1mg/kg 0.3mg/kg 0.03mg/kg 20pM MTD of non-masked TROP2-TCE (dosed by continuous IV infusion) >5,000x safety multiple (TRACTr : TCE) 0 200 400 600 800 1,000Maximum conc. (pg/mL) 0.3mg/kg 0.1mg/kg 0.03mg/kg IL-6 TNF IFNγ IL-2 No fever, no clinical signs of CRS Additional cytokines BLoQ IL-4, IL-5, IL-10, IL-13 Non-masked TROP2-TCE Adverse clinical signs consistent with CRS and healthy tissue toxicity: Fever, neurological effects GI, skin, kidney toxicity No adverse clinical signs or pathology changes consistent with a lack of measurable healthy tissue toxicity TROP2-TRACTr – IV bolusTROP2-TRACTr – IV bolus Large safety window may enable increased dose and higher intratumoral drug concentrations for stronger efficacy
Page 24
24 First-In-Class TROP2-TRACTr Opportunity Janux well-positioned to access high-value target with clinically validated TRACTr platform Opportunity for First-In-Class TROP2 targeted TCE Janux TROP2-TRACTr first-in-class opportunity combined with potential advantages over ADCs • Activity across full spectrum of TROP2 expression densities and tumor types • In vivo activity demonstrated where TROP2-ADCs have failed • Large safety multiple in NHP Robust Non-clinical Safety and Activity Rapid TRACTr Development Path Clinically validated TRACTr platform • Reduced risk of CRS and healthy tissue toxicity • Potential stronger efficacy and broader clinical benefit for patients across all levels of TROP2 expression over ADCs • Add new indications with unmet need into Janux portfolio TROP2-TRACTr for the treatment of TROP2 expressing solid tumors T cell binding domain (CD3) Tumor binding domain (TROP2) Half-life extension Albumin binding domain • Learnings from JANX007 and JANX008 help accelerate development • Previously deployed strategies have enabled rapid clinical POC • IND-enabling activities planned in 2H-2025
Page 25
Adaptive Immune Response Modulator (ARM) Platform Redesigned bispecific T-cell engagers
Page 26
26 Reimagining T-cell engagers to overcome TCE limitations for improved patient treatments Janux ARMs are designed to improve efficacy and safety of TCEs in oncology and I&I Janux ARM platform is designed to address key deficiencies of contemporary TCEs Efficacy Infections Healthy Tissue Tox CRS inpatient Depth & Durability Response Rate TCE Efficacy Infections Healthy Tissue Tox CRS outpatient Depth & Durability Response Rate ARM Contemporary TCEs Janux ARMs
Page 27
27 Robust T-cell expansion is a key mediator of successful anti-tumor immune responses Expanded memory reservoir replenishes effector cells to maintain immune response Adaptive T-Cell Immune Response *Reiner 2025, **Dreyzin 2025 • Tumor clearance • Checkpoint antibody responders* • CAR-T responders** Life-span Differentiation Self-renewal & expansion Effector functions - Cytotoxicity - TNFα, GZB, IFNƴ Transitional memory Central memory Effector memory Effector Naïve T-Cell Subsets and Functions
Page 28
28 Robust T-cell expansion is a key mediator of successful anti-tumor immune responses Expanded memory reservoir replenishes effector cells to maintain immune response Adaptive T-Cell Immune Response *Reiner 2025, **Dreyzin 2025 • Tumor clearance • Checkpoint antibody responders* • CAR-T responders** Ineffective Immune Response • Progressing tumors • Checkpoint antibody non-responders • CAR-T non-responders
Page 29
29 Recent clinical studies have shown that TCEs elicit minimal T-cell expansion in heme-onc and AID patients • Decline in cytolytic function has been reported in ALL patients treated with Blincyto (Ma 2024) • Naïve, central memory, effector memory, and effector subsets were unchanged following treatment • Temporary disease improvement has been reported for multiple TCEs in AID patients (EULAR 2025) • Naïve and central memory subsets were unchanged following Teclistamab treatment (Bucci, Schett EULAR 2025) • Reduced B-cell depletion after treatment with Blincyto, Talquetamab, and Teclistamab has been observed in multiple clinical trials (Verkleij 2024, Philipp 2022) Key question – can a bispecific T-cell engager be redesigned to improve T-cell expansion, depth and durability of response? TCE T-Cell Immune Response
Page 30
30 ARM demonstrates comparable potency with reduced cytokine release compared to TCE Healthy human PBMCs – similar data with CD4 T-cells D1 D3 D5 D7 0 50,000 100,000 150,000 200,000 250,000 pg/mL D1 D3 D5 D7 0 300 600 900 1,200 1,500 D1 D3 D5 D7 0 200 400 600 800 1,000 D1 D3 D5 D7 0 500 1,000 1,500 2,000 2,500 -2 -1 0 1 2 3 4 5 6 0 20 40 60 80 100 120 Log [pM] B-Cell Survival (%) B-Cell Depletion Cytokine Release IFNƴ TNFα IL-6 IL-2 -5 -4 -3 -2 -1 0 1 2 3 4 0 20 40 60 80 100 120 Log [pM] CD19 bispecifics CD20 bispecifics D1 D3 D5 D7 0 5,000 10,000 15,000 20,000 pg/mL D1 D3 D5 D7 0 300 600 900 1,200 1,500 D1 D3 D5 D7 0 200 400 600 800 1,000 D1 D3 D5 D7 0 50 100 150 200 250 T-Cell Expansion Complete B cell killing ARM improved expansion Reduced cytokine release with ARM -2 -1 0 1 2 3 4 5 6 1 2 4 8 16 32 64 128 256 Log [pM] CD8+ T-cell fold change -5 -4 -3 -2 -1 0 1 2 3 4 0.5 1 2 4 8 16 32 64 Log [pM] CD8+ T-cell fold change ARM TCE
Page 31
31 • ARM activity requires target cells • Expanded T cells post ARM treatment require drug to remain active (T cells do not become autoreactive post ARM treatment) Comparison of TCE and ARM CD8 profiles and B-cell depletion TCE treatment reduces effector populations which limits B-cell depletion ARM expands memory populations and maintains effector populations for complete B-cell depletion 0.125 0.5 2 8 32 128 512 2048 D1 D3 D5 D7 CD8 T-Cell Fold Change B-Cell Survival (%) 0.125 0.5 2 8 32 128 512 2048 D1 D3 D5 D7 CD8 T-Cell Fold Change B-Cell Survival (%) Limited B-cell depletion Complete B- cell depletion CD20-TCE CD20-ARM Large memory expansion Increased effector populations Nominal effector or memory expansion Tn Tscm Ttm Tcm Tem Teff Temra 0 0% 20% 40% 60% 80% 100% 120% 0 0% 20% 40% 60% 80% 100% 120%
Page 32
32 ARM demonstrates improved duration of T cell function compared to a TCE Provides potential to improve clinical durability and reduce infection risk ARM expands memory populations and maintains effector populations for a durable B-cell depletion response CD20-TCE CD20-ARM Tn Tscm Ttm Tcm Tem Teff Temra Learnings from clinical TCE programs* • Loss in T-cell function during dosing period has been reported for multiple oncology clinical programs • Blincyto, teclistamab, and talquetamab • Limited response durability in AID patients with Teclistamab and Blincyto reported ARM durability advantage • ARM maintains T-cell function • Improved durability of response compared to a TCE • Should decrease exhaustion mediated infection risk • Progressive loss of T cell function with TCEs is similar to that reported in the clinic *Philipp 2022, Verkleij 2024; Schett EULAR 2025 0% 20% 40% 60% 80% 100% 0.125 0.25 0.5 1 2 4 8 16 32 64 128 256 512 1024 2048 4096 D1 D7 D8 D10 D12 D14 CD8+ T-Cell Fold Change B-Cell (%) Cycle 1 Cycle 2 Memory and effector cells maintained Limited B-cell depletion Loss of effector populations Complete B- cell depletion 0% 20% 40% 60% 80% 100% 0.125 0.25 0.5 1 2 4 8 16 32 64 128 256 512 1024 2048 4096 D1 D7 D8 D10 D12 D14 CD8+ T-Cell Fold Change B-Cell (%) Cycle 1 Cycle 2
Page 33
CD19-ARM to Treat AID Patients Lead Program – Planned FIH Phase 1 for 1H2026
Page 34
34 • Prolonged autoreactive B cell depletion • Predominantly naïve B cell repopulation • Reduction of auto-antibodies • Durable medication free clinical responses CD19-ARM aims to reset the immune system of autoimmune disease (AID) patients Deep and rapid B cell depletion from blood and tissue followed by naïve B cell re-population Cell count Autoreactive B cells Normal B cells Days Year+Months Primarily Naïve B cell rebound CD19-ARM designed to drive prolonged drug free remissions as a fully off the shelf re-dosable compound in AID GOAL is to achieve extended drug free remissions Weeks T cell activation B cell aplasia in blood and lymphoid tissue Adaptive T cell response T-Cell expansion then contraction ARM single SC dose T cell expansion Normal B cell re-population B cell depletion T cell contraction B cell aplasia Immune reset Reduced CRS risk by design Reduced T cell exhaustion by design B cell depletion
Page 35
35 Deep B-cell depletion in periphery and tissues with a prolonged memory cell reset Single dose NHP results support an extended dosing interval in autoimmune patients CD19-ARM provides a wide B-cell depletion dosing range to optimize desired efficacy profile Deep Tissue B-cell DepletionRapid B-Cell Depletion Durable Memory B Cell Reset 0 100 200 300 400 500 600 700 800B cell count / μL blood Pre- 1wk 4wk 7wk 9wk 12wk dose Pre- 1wk 4wk 7wk dose 3 mpk SC 100 mpk SC Prolonged memory B-cell depletion Switched memory Unswitched memory Naive Immature & Transitional B cell phenotype 8wk Learnings from CD19-CAR T studies in AID patients • B-cell depletion within 1st month • Median of 3-months for naïve B-cell repopulation • Drug free remissions of >2-years have been reported • However, AID patient flares have recently been described* CD19-ARM efficacy profile is similar to CD19-CAR T • Rapid B-cell depletion occurs within days of dosing • Primarily naïve B-cell repopulation during first 3-months • Extended memory population reset • Ability to re-treat with a single-dose to address disease flares *EULAR 2025 0 200 400 600 800 0 7 14 21 28 35 42 49 56 63 70 77 84 Days post dose B cells in blood (cells / μL) 100mg/kg SC 2.5mg/kg SC Pre- dose Wide dosing range to optimize efficacy profile -1
Page 36
36 0.1mpk IV1mpk IV9mpk IV100mpk IV0.1mpk SC2.5mpk SC3mpk SC10mpk SC100mpk SC0.1mpk 0 4,000 8,000 12,000 16,000Peak IL-6 (pg/mL) mpk SC 0.01mpk IV0.1mpk IV1mpk pk IV 0.1mpk IV1mpk IV 0.1mpk SC1mpk SC0.01mpk pk SC 0.1mpk IV1mpk IV 0.1mpk SC1mpk SC0.1 μpk 0 CD19-ARM has best-in-class safety multiple in NHP relative to contemporary TCEs ARM overcomes CRS limitations of contemporary TCEs *Meetze 2023; †BLA-125557; ‡Engelberts 2020; ||BLA-761324; ₼Sun 2015; ₼BLA-761263; ₶Frances 2022; ₶BLA-761309 Information provided above is for illustrative purposes only and is not a head-to-head comparison. B-Cell Depletion Competitor’s B-cell depletion depth is limited by CRS dosing constraints CD19-ARM provides a ≥100x CRS safety multiple to enable maximum efficacy *CLN-978 Euthanasia* †Blincyto CD19-ARM CD19-ARM potential best-in-class profile combines efficacy without CRS to enable outpatient treatment opportunity Cytokine Release Euthanasia* 0.1mpk IV1mpk IV9mpk IV100mpk IV0.1mpk SC2.5mpk SC3mpk SC10mpk SC100mpk SC 0 200 400 600 800 1,000Peak IL-6 (pg/mL) Data N/A Data N/A ‡Epcoritamab Euthanasia|| Euthanasia|| ₼Mosunetuzumab₶Glofitamab -100 -80 -60 -40 -20 0 % change in B cells (from pre-dose to 1 week) Euthanasia ₶ pk SC 0.1 μpk IV 0.1mpk Euthanasia ₶ k IV 1mpk IV
Page 37
37 CD19-ARM demonstrates activity in multiple autoimmune patient samples Consistent B-cell depletion in disease patient PBMCs ARM provides opportunity for deep / durable responses in multiple autoimmune indications 0.1 1 10 100 Healthy MG IIM RA SLE EC50 (pM) 0 20 40 60 80 100 Healthy MG IIM RA SLE B cell killing (%) Potent B-Cell Depletion Full B-Cell Depletion Systemic Lupus Erythematosus (SLE) Rheumatoid Arthritis (RA) Myasthenia Gravis (MG)
Page 38
38 Phase 1 study design - first patient treated in HNV trial planned in 1H2026 HNV study to rapidly understand B-cell depletion and CRS risk, AID study to evaluate multiple indications Healthy Normal Volunteer (HNV) Study Rapidly understand B-cell depletion and CRS risk Day 0 Day 28 Month 3-6 CD19-ARM Dose End of DLT Period Observation Period Autoimmune Patient Study AID Indications Day 0 CD19-ARM 1st Dose Month 3-6 Dose Period Observation Period Month 6-12 Key Phase 1 Evaluations • Safety and tolerability • CRS/ICANS • Dose finding • Pharmacokinetics • T-cell expansion • B-cell depletion, immune reset and durability • Autoantibody serology • ARM platform validation
Page 39
39 Key CD19-ARM developments ARM Platform Dosing Convenience Human Dose Projection Clinical Development • CD19-ARM planned FIH Phase 1 for 1H2026 • Regulatory filing planned for 4Q2025 • GMP bispecific antibody manufacturing in-progress • Human efficacious dose projection range is 0.07-0.17 mg/kg SC (5-12 mg total dose) • Based upon the fully efficacious dose of 3 mg/kg SC in cyno • CD19-ARM is more potent in human PBMCs compared to cyno PBMCs used to assess MABEL • SC dosing coupled with lack of CRS highlights potential for community-based outpatient treatment • Extended dosing interval without step-doses highlights ease-of-use advantage • ARM pipeline is advancing - BCMA, CD20, BAFFr, and trispecifics • Solid tumor evaluations are in-progress
Page 40
40 CD19-ARM: Best-In-Class Opportunity Janux is leading the development of novel TCEs that address efficacy and safety limitations TRACTr and ARM platforms provide the opportunity to develop best-in-class drugs CD19-ARM with potential best-in-class profile provides opportunity to match CD19 CAR-T efficacy as an off-the-shelf, outpatient therapy Expertise At All Stages of Drug Development Rapid Path to Clinical PoC Differentiated ARM Platform • Reduced risk of CRS with outpatient/community potential • Large safety window, high dose flexibility, deep B cell depletion with immune reset potential • Durable T cell activity may reduce risk of infection • Full cytolytic activity • Reduced cytokine release • T cell expansion, longer duration, less T cell exhaustion B cell depletion has proven clinical efficacy Advantageous design principles • HNV study (planned 1H2026) accelerates PoC • B-cell depletion, safety, immune reset • HNV PK/PD data informs AID study • Demonstrated track record of non-clinical, manufacturing, and clinical TCE development • Experienced leadership poised to drive best-in-class platform opportunity • World renowned investigators excited to partner with Janux
Page 41
JanuxRx.com David Campbell, Ph.D. President and CEO 10955 Vista Sorrento Parkway San Diego, CA 92130 dcampbell@januxrx.com