Slide 1: First-in-Human Results With IMA401, a MAGEA4/8-targeted TCR-based Bispecific
PRESENTED BY: First - in - Human Results With IMA401 , a MAGEA4 /8 - targeted T - cell Receptor - based Bispecific T - cell Engager ( TCER ), in Recurrent or Refractory Solid Tumors Martin Wermke¹ , Dirk Jaeger² , Annalen Bleckmann³ , Manik Chatterjee⁴, Stefanie Groepper ⁵, Daniel Heudobler ⁶, Judit
Slide 2: Key Takeaways
PRESENTED BY: Key Takeaways • TCR - based therapies enable immune recognition of intracellular tumor antigens presented by cell - surface HLA, expanding the therapeutic landscape beyond targets accessible to conventional immunotherapies • IMA401 is a novel TCR - based bispecific T - cell engager tar
Slide 3: Target Biology of IMA401-Targeted MAGEA4/8 Peptide
PRESENTED BY: Target Biology of IMA401 - Targeted MAGEA4/8 Peptide Prof. Dr. med. Martin Wermke, Abstract #2507 45% 40% 40% 30% 20% 65% Cutaneous melanoma n = 195 HNSCC n = 338 Ovarian carcinoma n = 351 sqNSCLC n = 91 Esophageal carcinoma n = 57 Bladder carcinoma n = 278 IMA401 target peptide shows
Slide 4: IMA401 Designed to Improve Efficacy and Reduce Risk of CRS
PRESENTED BY: CD3/TCR Activated T cell Tumor Cell MAGEA4/8 pHLA IMA401 x Anti - tumor Activity High - affinity MAGEA4/8 pHLA binding (K D = 1.7 nM ; BLI) x Antibody - like format with half - life extension (HLE) Long half - life of 2 - 3 weeks a x Optimized tolerability Low binding to TCR/CD3 - expr
Slide 5: IMA401 Phase 1 Basket Trial in Solid Tumors: Objectives and Eligibility
PRESENTED BY: IMA401 Phase 1 Basket Trial in Solid Tumors : Objectives and Eligibility Prof. Dr. med. Martin Wermke, Abstract #2507 Objectives Primary: • Determine MTD and/or RP2D in monotherapy and in combination with pembrolizumab Secondary: • Assess safety and tolerability • Evaluate initial anti
Slide 6: Phase 1 Basket Trial of IMA401 in MAGEA4/8+ Solid Tumors
PRESENTED BY: Phase 1 Basket Trial of IMA401 in MAGEA4/8+ Solid Tumors Prof. Dr. med. Martin Wermke, Abstract #2507 0.18 mg 0.54 mg 1.8 mg 0.06 mg 1.2 mg 0.02 mg 0.0066 mg 2.0 mg 1.0 mg 1.5 mg 2.5 mg Phase 1a dose escalation completed 1.8 mg 1.2 mg 2.0 mg 1.0 mg 1.5 mg Dose selection : MTD not reach
Slide 7: Baseline Characteristics
PRESENTED BY: RP2D (1 - 2 mg) All Dose Levels Baseline Characteristics IMA401 + Pembrolizumab b n=12 IMA401 (Monotherapy) n=32 IMA401 ± Pembrolizumab n=61 63 (33, 77) 62 (19, 82) 62 (19, 82) Age (years) , median (min, max) 12 (100)/ 0 (0) 19 (59)/ 13 (41) 39 (64)/ 22 (36) Sex , m ale/female n (%) 6
Slide 8: Tolerability of IMA401 Monotherapy
PRESENTED BY: Tolerability of IMA401 Monotherapy Prof. Dr. med. Martin Wermke, Abstract #2507 IMA401 (Monotherapy) A ll treated patients > 2 mg n=7 1 - 2 mg (RP2D) n=32 All Dose Levels N=61 Treatment - related Adverse Events (safety analysis set) ≥ Grade 3 All Grades ≥ Grade 3 All Grades ≥ Grade 3 A
Slide 9: Tolerability of IMA401 + Pembrolizumab
PRESENTED BY: IMA401 + Pembrolizumab IMA401 (Monotherapy) 1 - 2 mg (RP2D) b n=12 1 - 2 mg (RP2D) n=32 Treatment - related Adverse Events (safety analysis set) ≥ Grade 3 All Grades ≥ Grade 3 All Grades TRAEs a , n (%) 3 (25) 11 (92) 16 (50) 28 (88) Any TRAE 0 5 (42) 0 12 (38) Cytokine release syndrom
Slide 10: Efficacy of IMA401 at RP2D ± Pembrolizumab
PRESENTED BY: Efficacy of IMA401 at RP2D “ Pembrolizumab Prof. Dr. med. Martin Wermke, Abstract #2507 H&N b ( n= 14) BOR (RECIST 1.1) PD SD PR cPR Ongoing response /disease control Other a (n=27, 14 different indications) IMA401 monotherapy IMA401 + Pembrolizumab 29 % ( 4/14 ) cORR 64% (9/14) DCR H&
Slide 11: Durable Responses to IMA401 ± Pembrolizumab in Patients with H&N Cancer
PRESENTED BY: 0 6 12 18 24 -100 -50 0 50 100 Months post First IMA401 Infusion C h a n g e i n S u m o f L o n g e s t D i a m e t e r o f T a r g e t L e s i o n s f r o m B a s e l i n e [ % ] BL PR ⯈ Palliative Radiotherapy + ⯈ ⯈ ⯈ ⯈ Durable Responses to IMA401 “ Pembrolizumab in Patien
Slide 12: Patient Case: Partial Response after IMA401 + Pembrolizumab in H&N Cancer
PRESENTED BY: Patient Case: Partial Response after IMA401 + Pembrolizumab since 5+ months in H&N Cancer Prof. Dr. med. Martin Wermke, Abstract #2507 Scans courtesy of treating physician Dr. Moritz Kleemiß , UK Bonn; BOR, best overall response; H&N, head and neck; HNSCC, squamous cell carcinoma of th
Slide 13: Patient Case: Partial Response after IMA401 + Pembrolizumab in sqNSCLC
PRESENTED BY: Patient Case: Partial Response after IMA401 + Pembrolizumab in sqNSCLC Prof. Dr. med. Martin Wermke, Abstract #2507 a Treatment start 5 weeks after last prior systemic therapy; scans courtesy of treating physician Prof. Dr. Martin Wermke , TU Dresden; BOR, best overall response; ICI, i
Slide 14: MAGEA4/8 + PRAME Bispecific Dual Targeting in sqNSCLC
PRESENTED BY: MAGEA4/8 + PRAME + IMA401 MAGEA4/8 + IMA402 PRAME Bispecific Dual Targeting in sqNSCLC Prof. Dr. med. Martin Wermke, Abstract #2507 MAGEA4/8 + PRAME + >90% MAGEA4/8 OR PRAME of sqNSCLC Double Positive ~60% of sqNSCLC Representative duplex IF image of a double positive human sqNSCLC tum
Slide 15: Key Takeaways
PRESENTED BY: Key Takeaways • TCR - based therapies enable immune recognition of intracellular tumor antigens presented by cell - surface HLA, expanding the therapeutic landscape beyond targets accessible to conventional immunotherapies • IMA401 is a novel TCR - based bispecific T - cell engager tar
Slide 16: Thank You – Trial Participants & Caregivers
PRESENTED BY: 16 IMA401 Phase 1 Trial Sponsor: Immatics Thank You – Trial Participants & Caregivers Prof. Dr. med. Martin Wermke, Abstract #2507 University Hospital, Dresden University Hospital Bonn Charité – University Medicine Berlin University Hospital Heidelberg TUM University Hospital Munich Ge
Slide 17: Appendix
PRESENTED BY: Appendix Prof. Dr. med. Martin Wermke, Abstract #2507
Slide 18: IMA401 Bispecific Pharmacokinetics in Patients
PRESENTED BY: IMA401 Bispecific Pharmacokinetics in Patients Prof. Dr. med. Martin Wermke, Abstract #2507 Shown are the median and interquartile ranges (25 - 75%) for all patients with evaluable PK samples that received biweekly target doses at or above 1 mg. Median half - life: 17.5 days (n=22) Dat
Slide 19: Patient Disposition
PRESENTED BY: Patient Disposition Prof. Dr. med. Martin Wermke, Abstract #2507 Dose groups are shown according to highest actual IMA401 dose received at any time point, as initial target dose or via intrapatient dose escalation and as monotherapy or combination with pembrolizumab. Efficacy populatio
Slide 20: Baseline Characteristics for IMA401 at RP2D in H&N Cancer
PRESENTED BY: Baseline Characteristics for IMA401 at RP2D ± Pembrolizumab in Patients with H&N Cancer Prof. Dr. med. Martin Wermke, Abstract #2507 This Phase 1 basket trial was not specifically designed for H&N cancer ; therefore , some H&N subclassification data may be limited or not fully conclusi
Slide 21: Summary of AEs in Patients treated with IMA401 ± Pembrolizumab
PRESENTED BY: Summary of AEs in Patients treated with IMA401 “ Pembrolizumab Prof. Dr. med. Martin Wermke , Abstract #2507 a IMA401 dose in pembrolizumab expansion cohorts were 1 mg (n=8) or 1.5 mg (n=4); b Two of the three deaths were unrelated to IMA401 and / or pembrolizumab . One treatment - unr
Slide 22: Tolerability of IMA401 at RP2D in all Indications and H&N Cancer
PRESENTED BY: Tolerability of IMA401 at RP2D “ Pembrolizumab in all Indications and in Patients with H&N Cancer IMA401 RP2D (1 - 2 mg) ± Pembrolizumab IMA401 RP2D (1 - 2 mg) ± Pembrolizumab H&N n=14 all indications n=44 Treatment - related Adverse Events (safety analysis set) ≥ Grade 3 All Grades ≥
Slide 23: Best Change in Target Lesions and BOR
PRESENTED BY: PR -100 -50 0 50 100 -11 -6 0 18 29 56 62 -100-100 -75 -73 -70 -66 -62 -50 -43 -39 -25 -22 -20 -19 -19 -15 -15 -14 -12 -7 -6 0 1 2 3 9 10 13 13 19 19 20 22 38 40 67 69 96 -36 -31 -4 6 9 14 29 98 B e s t % C h a n g e i n S u m o f L o n g e s t D i a m e t e r o f T a r g e t L e s i o
Slide 24: Clinical Responses of IMA401 at RP2D in Patients with H&N Cancer
PRESENTED BY: Clinical Responses of IMA401 at RP2D ± Pembrolizumab in Patients with H&N Cancer a Target lesion sum of diameter ; b Max change not shown due to clinical progression before post - infusion scan ; BOR, best overall response; (c)PR, ( confirmed ) partial response; H&N, head and neck canc
Slide 25: Thank you
PRESENTED BY: Thank you Prof. Dr. med. Martin Wermke, Abstract #2507