Innate Pharma Sa Class A · EURONEXT:IPH
Innate Pharma Sa Class A — Investor Day (February 2025)
43 slides from Innate Pharma Sa Class A's investor day presentation, Feb 5, 2025
Slide 1: Nectin-4 ADC Update
Nectin-4 ADC Update New York, NY Jonathan Dickinson │CEO, Innate Pharma February 5th, 2025
Slide 2: Disclaimer on Forward-Looking Information and Risk Factors
Disclaimer on Forward-Looking Information and Risk Factors This document has been prepared by Innate Pharma S.A. (the “Company”) solely for the purposes of a presentation to investors concerning the Company. This document is not to be reproduced by any person, nor to be distributed. This document co
Slide 3: Agenda
Agenda 1. Introduction Jonathan Dickinson │Chief Executive Officer, Innate Pharma 2. Current Nectin-4 landscape Yohann Loriot | Deputy Chair of the Department of Early Drug Development, Gustave Roussy, Université Paris-Saclay 3. IPH4502 Preclinical data Yannis Morel │EVP, Chief Operating Officer, In
Slide 4: 2025: Focus on Strategic Growth Pillars
2025: Focus on 3 Strategic Growth Pillars NK-cell engagers Antibody Drug Conjugates Current Late-Stage Assets • IPH6501 (CD20) ANKET® Phase 1 • IPH4502 (Nectin-4) IND cleared, • Lacutamab positive Phase 2 data, Phase 1 start Jan 2025 FDA feedback on next steps, • IPH6101 (CD123) ANKET ® Phase 2 Part
Slide 5: Key Takeaways
Key Takeaways Innate has a solid strategy to deliver long term growth with proprietary and partnered assets and we have 8 key programs in clinical stages of development • DRIVING FORWARD OUR ANKET® CLINICAL PORTFOLIO • Phase 1/2 clinical trial underway with IPH6501 in B-cell NHL, agreement with IFLI
Slide 6: A Robust Pipeline of Innovative, Differentiated Proprietary & Partnered Assets
A Robust Pipeline of Innovative, Differentiated Proprietary & Partnered Assets Pre-Clinical Phase 1 Phase 2 Phase 3 IPH67 IPH6501 (CD20-IL2v) IPH6101/SAR’579 (CD123) Monalizumab (NKG2A) Undisclosed, solid tumors B-NHL Blood cancers (Phase 1/2) Unresectable Stg III NSCLC IPH81 IPH6401/SAR’514 (BCMA)
Slide 7: Nectin-4 landscape
& innate pharma BA Nocti Nectin-4 landscape WY
Slide 8: Pr Yohan Loriot, MD, PhD
Pr Yohan Loriot, MD, PhD Professor of Medicine at Paris-Saclay University and Deputy Chair of the Department of Early Drug Development at Gustave Roussy, Villejuif, France • Medical oncologist specialized in genitourinary cancers* • Research focuses on drug development, particularly in connection wi
Slide 9: Shifting ADC Landscape: Growth of Topoisomerase Inhibitors based ADCs
Shifting ADC Landscape: Growth of Topoisomerase Inhibitors based ADCs ADC approved by payload 255 ADCs (Clinical) DNA Tubulin inhibitor Damaging Topo1 inhibitor agent 3 Immunomodulator 6 DNA damaging agent 3 Tubulin Degrader inhibitor Topoisomerase inhibitor ADC Beacon by Hanson Wade, Nov 2024 Since
Slide 10: Nectin-4 ADC Landscape: MMAE-based ADC Approved; Next Generation
Nectin-4 ADC Landscape: MMAE-based ADC Approved; Next Generation Includes Tubulin and Topoisomerase Inhibitor-based ADCs IPH4502 • EV is the only anti-Nectin-4 TopoI ADC approved (UC) LY4052031 MK-3120 ADCs (SKB41) • Most advanced new LY4101174 aNectin-4 ADCs have tubulin SHR-A2102 BAT8007 inhibitor
Slide 11: Enfortumab Vedotin is approved in LA/mUC in monotherapy and PD-1 combination
Enfortumab Vedotin is approved in LA/mUC* in monotherapy (3L) and PD-1 combination (1L). Relapses create a growing medical need in post-EV setting 3L LA/mUC Phase 3 EV-301 EV vs chemotherapy 1.25 mg/kg IV D1+D8+D15 of 28D cycle ORR 40.6% vs. 17.9% Median PFS 5.55 mo vs. 3.71 mo Median OS 12.91 mo vs
Slide 12: Enfortumab Vedotin treatment related adverse events
Enfortumab Vedotin treatment related adverse events Phase 3 EV-301 Phase 3 EV-302/KEYNOTE-A39 TRAE 3L+ la/mUC 1L la/mUC Serious adverse reactions 22.6% (vs 23.4%) 27.7% (incl. Urinary tract infection, Acute kidney injury, Pneumonia) (incl. Rash, Acute kidney injury, Pneumonitis/ILD) All grades 48.0%
Slide 13: Beyond bladder, not validated signs of activity with Nectin-4-ADCs
Beyond bladder, not validated signs of activity with Nectin-4-ADCs MMAE-Based Nectin-4 ADC TopoI ADC BT8009 Nectin-4 Enfortumab Vedotin Zelenectide 9MW2821 CRB-701 SHR-A2102 expression pevedotin Phase 3 EV-301 N=38 EV-naïve n=37, ORR 62.2% N=9, ORR 44% Urothelial 2L+ ORR 41% ORR 45% (ESMO24) (ASCO24
Slide 14: Next generation of Nectin-4 ADCs to overcome challenges associated with approved therapy
Next generation of Nectin-4 ADCs to overcome challenges associated with approved therapy Next Generation Nectin-4 ADC Low and heterogenous Higher bystander effect Nectin-4 expression to address low and Limited activity heterogenous level of Nectin-4 Nectin-4 Different payload ADC MMAE Resistance to
Slide 15: IPH4502 – Preclinical data
IPH4502 – Preclinical data 15
Slide 16: Introduction to Nectin-4
Introduction to Nectin-4 Nectin-4 is a type I Overexpressed in Expression associated transmembrane adhesion multiple cancers, with tumor proliferation, molecule with limited expression making it a relevant metastasis, in healthy adult tissues tumor target and with poor prognosis Urothelial cancer Ne
Slide 17: A differentiated Nectin-4 targeted ADC with potential in low expressing and Padcev resistant tumors
IPH4502: A differentiated Nectin-4 targeted ADC with potential to show efficacy in moderate to low Nectin-4 expressing and Padcev resistant tumors OPPORTUNITIES 100 No Nectin-4 drug approved % of Nectin-4 expressing 80 • PADCEV (enfortumab vedotin, EV) is approved in bladder cancer where tumor sampl
Slide 18: IPH4502: A novel and differentiated Nectin-4 DAR8 exatecan ADC
IPH4502: A novel and differentiated Nectin-4 DAR8 exatecan ADC Phase 1 start in Jan 25 Payload Exatecan, Binder a Topoisomerase I inhibitor Proprietary humanized • Active in EV/MMAE-resistant models anti-Nectin-4 Antibody • Higher Bystander Effect than EV, • High affinity leading to stronger activit
Slide 19: IPH4502 recognizes Nectin-4 on a different epitope and exhibits higher solubility than EV
IPH4502 recognizes Nectin-4 on a different epitope and exhibits higher solubility than EV Hydrophobicity HIC IPH4502 TSKgel Butyl-NPR TRASTUZUMAB DXd SACITUZUMAB GOVITECAN Normalized absorbance ENFORTUMAB VEDOTIN Retention time 19
Slide 20: IPH4502 is a potent Nectin-4 ADC in vitro and in vivo
IPH4502 is a potent Nectin-4 ADC in vitro and in vivo IPH4502 induces Nectin-4+ IPH4502 demonstrates robust cell killing in vitro efficacy in a xenograft model Mean tumor volume (mm3) 1500 Mean tumor volume (mm3) 1500 1000 1000 500 500 0 0 20 20 30 30 40 40 50 50 Days Days post post engraftment engr
Slide 21: IPH4502 demonstrates more efficient internalization than other Nectin-4 ADC
IPH4502 demonstrates more efficient internalization than other Nectin-4 ADC mAb internalization Internalization of naked antibodies coupled to pHAb amine in Nectin-4 expressing SUM190 PT cells was monitored at 24h E = mAb having the amino acid sequence of Enfortumab; LY = humanized 15A7.5 mAb from p
Slide 22: IPH4502 demonstrates higher internalization and cytotoxicity
IPH4502 demonstrates higher internalization and cytotoxicity than 15A7.5-PSAR10-exatecan Internalization Cytotoxicity 1500 IPH4502-mAb Cell viability (Luminescence) 15A7.5-mAb 1×10 7 IPH4502 15A7.5-PSAR10-Exa Fluorescence (AU) IC 8×10 6 1000 IC-Exa 6×10 6 4×10 6 500 2×10 6 0 0 01 01 10 1 1 1 0 00 0.
Slide 23: IPH4502 shows stronger anti-tumor activity than EV in multiple PDX models
IPH4502 shows stronger anti-tumor activity than EV in multiple PDX models from UC patients Enfortumab vedotin IPH4502 Mice were treated with the same dose (4mg/kg) for both ADCs at day 0 (randomization) and day 7 Tumor Growth Inhibition (TGI) = relative change in tumor volume compared to the initial
Slide 24: IPH4502 shows efficacy across Nectin-4 expression levels and superior activity to EV
IPH4502: Shows efficacy across various Nectin-4 expression levels and demonstrates superior activity to EV in bladder PDX models H-score: 300 H-score: 180 H-score: 100 Nectin-4 expression 2000 2000 2000 Vehicle Tumor volume (mm3) Tumor volume (mm3) Tumor volume (mm3) 1500 1500 1500 EV 4 mg/kg 1000 1
Slide 25: IPH4502 bystander effect in heterogenous Nectin-4 expressing tumors
IPH4502: Demonstrates in vivo potential for efficacy in heterogenous Nectin-4 expressing tumors via target-dependent bystander effect Nectin-4+ cells Nectin-4 KO cells Nectin-4+ cells + Nectin-4 KO cells Tumor volume (mm3) In vivo bystander killing Address heterogeneous Nectin-4 expression 25
Slide 26: IPH4502 shows anti-tumor efficacy in a TNBC PDX model
IPH4502 shows anti-tumor efficacy in a PDX model from Nectin-4+ cancer indication beyond bladder IPH45 4 mg/kg PDX model of TNBC EV 4 mg/kg Treatment Vehicle IPH4502 (4 mg/kg) TNBC Tumor volume (mm3) Nectin-4 2000 2000 H-score: 200 1000 1000 0 0 0 15 30 0 15 30 Days post treatment n=10 mice/group 26
Slide 27: ABC transporters expression correlates with resistance to enfortumab vedotin
ABC transporters expression correlates with resistance to enfortumab vedotin in urothelial carcinoma In metastatic lesions, Nectin-4 is lower and ABC transporter expression in primary tumor ABC transporter expression is increased or metastasis correlates with resistance Kijima 2024 - Predictive role
Slide 28: IPH4502 demonstrates efficacy in EV-primary refractory model
IPH4502 demonstrates efficacy in EV-primary refractory model MMAE is a substrate of the multi-drug resistance protein 1 (MDR1) Activity of IPH4502? Treatment Vehicle EV IPH4502 EV then IPH4502 1500 1500 1500 1500 Tumor volume (mm3) Tumor volume (mm3) Tumor volume (mm3) Tumor volume (mm3) 1000 1000 1
Slide 29: Nectin-4 remains highly expressed in EV-relapsed cancer patients
Nectin-4 remains highly expressed in EV-relapsed cancer patients Nectin-4 expression was assessed by IHC in fresh biopsies from sites of tumor progression following EV from 3 patients Liver metastasis Lymph node metastasis Duodenal metastasis Nectin-4 expression is conserved in high grade UC patient
Slide 30: IPH4502 has anti-tumor activity in a PDX-model of acquired EV-resistance
IPH4502 has anti-tumor activity in a PDX-model of acquired EV-resistance Generation of a UC PDX model acquiring resistance to EV following repetitive injections: H-score: 200 EV-sensitive EV-resistant H-score: 200 F659 UC F659R UC PDX model PDX model Treatment EV IPH4502 EV IPH4502 Vehicle Vehicle (
Slide 31: IPH4502 shows increased activity in combination with anti-PD-1
IPH4502 shows increased anti-tumor activity in combination with anti-PD-1 in an EV-refractory model Vehicle EV Vehicle EV IPH4502 1500 1500 1000 1000 Treatment 500 500 0 0 20 40 60 20 40 60 anti-PD-1 Combination Combination Anti-PD-1 EV+anti-PD-1 IPH4502+anti-PD-1 1500 1500 1500 Tumor volume (mm3) 1
Slide 32: IPH4502 has high ADC exposure and minimal exatecan systemic release in NHP
IPH4502 has high ADC exposure and minimal exatecan systemic release in NHP ADC Mean concentration (ng/mL) 1000000 Total Ab 100000 Free toxin 10000 Total Ab LLOQ 1000 100 10 1 Free toxin LLOQ 0.1 1 8 15 22 29 36 43 50 57 Days GLP toxicology study: IPH4502 was administered at 30 mg/kg IV with 30 minut
Slide 33: IPH4502 has minimal exatecan systemic release in NHP
IPH4502 has minimal exatecan systemic release in NHP Free-toxin: Cmax EV ETX22 IPH4502 At Tmax = 48 or 60h At Tmax = 2 or 6 h At Tmax = 4.5h 12 12 12 Cmax (ng/ml) Cmax (ng/ml) 9 9 Cmax (ng/ml) 9 6 6 6 3 3 3 < LOQ LOQ 0 0 0 g /kg g/kg g/kg g /kg g /kg g /kg g /kg m m m m 1m 3m 6m 10 20 10 30 Values r
Slide 34: IPH4502 has broad potential in Nectin-4 expressing solid tumors
IPH4502 has broad potential in Nectin-4 expressing solid tumors • IPH4502 is a next-generation differentiated Nectin-4 exatecan ADC with high internalization and bystander effect • Linker’s hydrophilicity and stability translate into high ADC exposure and low release of free exatecan into cynomolgus
Slide 35: IPH4502 – Clinical development plan
IPH4502 – Clinical development plan 35
Slide 36: Assumptions for IPH4502 Clinical plan
IPH4502 Assumptions for IPH4502 Clinical plan IPH4502 to overcome Nectin-4 ADCs limitations • High Bystander effect Broader therapeutic window • High Internalization • Non-competitive epitope vs EV Potential beyond Bladder • Superior efficacy to EV in bladder cancer models with low ↑ activity in low
Slide 37: IPH4502 potential in solid tumors: UC and Beyond
IPH4502 potential in solid tumors: UC and Beyond IPH4502 potential benefit vs MMAE ADCs UC Expand beyond UC Address growing unmet need of High potential in several tumor types not post-Padcev mUC patients* responsive nor addressed by MMAE ADCs Move up to 1L mUC in combination with PD1 with low/med a
Slide 38: Large addressable market with significant upside
Large addressable market with significant upside Indications included in the Phase 1 dose escalation >200K US/EU patients 100-200K US/EU patients <100K US/EU patients Bladder HNSCC Cervical NSCLC Ovarian Esophageal Breast GEJ Melanoma CRC Prostate 38
Slide 39: IPH4502 Phase 1 study design
IPH4502 Phase 1 study design US and EU DOSE ESCALATION DOSE OPTIMIZATION STUDY POPULATION DESIGN FEATURES DESIGN FEATURES OBJECTIVES • Step-wise dose escalation to determine • Randomize at least 2 dosing schedules Solid tumor types MTD for further dose optimization Primary Objectives: with clinical
Slide 40: Biomarker plan
IPH4502 Biomarker plan % positivity Nectin-4 expression Negative Low and homogeneous The clinical program includes a biomarker plan to identify patient populations who most benefit from the IPH4502 treatment • Analysis of Nectin-4 expression in cancer tissue from study patients High and heterogeneou
Slide 41: Soluble Nectin-4 is higher in cancer patients than in healthy donors
Soluble Nectin-4 is higher in cancer patients than in healthy donors ✱✱✱✱ 6000 N=40 A soluble form of Nectin-4 (sNectin-4), has been identified [sNectin-4] (pg/mL) in several other tumor types 4000 such as ovarian cancer (Derycke et al. 2010), breast N=15 2000 cancer (Fabre-Lafay et al. 2007), or NS
Slide 42: Multiple Clinical Milestones to be Delivered in Mid-term
IPH4502 Multiple Clinical Milestones to be Delivered in Mid-term FPI: First Patient In; SOC: standard of care IPH4502 Phase 1 in Nectin-4 expressing tumors Start basket trial in combination with SOC Preliminary safety and activity FPI in Phase 1 signal in tumor types with low Readout from dose Dose
Slide 43: Thank you
Thank you www.innate-pharma.com investors@innate-pharma.fr EURONEXT : IPH.PA NASDAQ : IPHA