Immuneering Corporation · NASDAQ:IMRX
Immuneering — Investor Presentation (April 2023)
47 slides from Immuneering's investor presentation, Apr 18, 2023
Slide 1: Building a Universal-RAS Franchise
Building a Universal - RAS Franchise Nasdaq: IMRX APRIL 2023 Investor Presentation
Slide 2: Forward-looking statements
2023 Corporate Presentation 2 This presentation contains forward - looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 . All statements contained in this presentation that do not relate to matters of historical fact should be considered forward - looking sta
Slide 3: Differentiated Approach
Differentiated Approach • Targeting Universal - RAS patient population versus limited single mutation targeted approaches • Once - Daily Oral Dosing • Deep cyclic inhibition targeted, based on: • Manyfold higher C MAX • and short half - life • Approach designed to spare healthy cells and potential t
Slide 4: Development Pipeline
PROGRAM INDICATION DISCOVERY IND - ENABLING PHASE 1 PHASE 2 PHASE 3 ANTICIPATED MILESTONES IMM - 1 - 104 Universal - RAS Phase 1/2a Trial Enrolling; RP2D expected in early 2024 IMM - 6 - 415 Universal - MAPK IND filing expected in Q4 2023 Multiple additional programs in discovery phase Development P
Slide 5: IMM-1-104
IMM-1-104 @ Immuneering
Slide 6: Target Profile
6 IMM - 1 - 104 Target Profile Potential for Universal - RAS Activity Deep Cyclic Inhibition ; Once - Daily Oral Dosing Short plasma half - life to minimize drug trough Initially being developed as Monotherapy Designed to Resist CRAF - bypass in RAS mutant tumors • Phase 1 recruiting all - comer RAS
Slide 7: Potential: Universal-RAS
7 IMM - 1 - 104’s Potential: Universal - RAS * ' * $ * 5 * 6 4 * .5$62WKHU $OOQGLFDWLRQV *(1( 15$6 +5$6 .5$6 NRAS (14.12%) Targeted KRAS G12C • Based on 27,461 out of 148,268 (18.5%) patients with RAS - mutated tumors in the AACR GENIE database, v13.0 • Percentage of overall mutation shown under RAS
Slide 8: Deep Cyclic Inhibition mechanism
8 MoA Target Engagement GOAL : Prevent MAPK - pathway bypass events, for expanded activity into RAS mutant setting Near - Zero Drug Trough GOAL : Short plasma half - life to improve tolerability and limit adaptive resistance, so every day is a drug holiday Dramatic PK C MAX Pulse GOAL : Achieve many
Slide 9: Initial Phase 1 PK, PD and Safety Data
9 Initial Phase 1 PK, PD and Safety Data for IMM - 1 - 104 Short Half - life Observed Observed IMM - 1 - 104 half - life of approximately 2 hours, as projected in Immuneering’s preclinical modeling Deep Cyclic Inhibition (DCI) Initial pharmacokinetic (PK), pharmacodynamic (PD) and safety data suppor
Slide 10: Patient Status Summary for Phase 1 Dose Escalation
10 Patient Status Summary for IMM - 1 - 104 Phase 1 Dose Escalation Clinical data timeline reported through April 10th, 2023 (i.e., ~20 weeks since first patient dosed) # Patient RAS Mutation Dose Level Dose C1D1 (t 1/2 ) C1D15 (t 1/2 ) Mean (t 1/2 ) IMM - 1 - 104 Status 1. PANCREATIC KRAS - G12D I
Slide 11: Pharmacodynamic Inhibition of pERK
0 3 6 9 12 15 18 21 24 0 250 500 750 1000 1250 1500 1750 2000 2250 2500 0 10 20 30 40 50 60 70 80 90 100 Time (hours) I M M - 1 - 1 0 4 [ n g / m L ] AACR poster PK/PD: Pt.3 & Pt.4 ERK % Baseline Pt.3 PK (ng/mL) p h o s p h o : t o t a l - E R K ( % B a s e l i n e ) Pt.4 PK (ng/mL) Pt.3 p/t-ERK (%
Slide 12: Phase 1/2 Clinical Trial Plan
IMM - 1 - 104: Phase 1/2 Clinical Trial Plan * Solid tumor, all comer with evidence of RAS mutation ** Simon 2 - Stage Design. Proposed tumor types may change based upon preclinical PGx studies and clinical function review First Time in Humans • RAS mutated Pancreatic (PAAD) (~ 40 pts) • RAS Mutated
Slide 13: Trial Sites
13 Phase 1 Sites ClinicalTrials.gov Identifier: NCT05585320 MD Anderson Cancer Center › Houston, Texas, United States, 77030 › Principal Investigator: Shubham Pant, MD United States, Texas NEXT Oncology › San Antonio, Texas, United States. 78229 › Principal Investigator: David Sommerhalder , MD MD W
Slide 14: IMM-1-104 Preclinical Data
IMM-1-104 Preclinical Data @ Immuneering
Slide 15: Demonstrated Universal-RAS Potential
IMM - 1 - 104 Demonstrated Universal - RAS Potential 15 Humanized 3D - TGA RAS, RAF mutation Response # Non - Response # NRAS G12 2 0 NRAS G13 1 0 NRAS Q61 17 2 KRAS A146 1 0 KRAS G12 36 8 KRAS G13 ^ 3 1 KRAS Q61 3 0 HRAS G13 * 1 0 BRAF (Class I or II) 21 4 Total 85 (85.0%) 15 (15.0%) ^ 1 model also
Slide 16: Humanized 3D-TGA Pharmacogenomics Modeling
Humanized 3D - TGA Pharmacogenomics (PGx) Modeling 16 Nair, et al. 2023, AACR: National Meeting, Orlando, FL • Cell lines tested in 3D - TGA (N=132) were assigned response of sensitive (IC50 < 1uM), intermediate (IC50 ≥ 1 and >25% reduction at 10uM), and resistant otherwise • The dark line on each p
Slide 17: Demonstrated Universal-RAS Potential: Tumor Models
IMM - 1 - 104 Demonstrated Universal - RAS Potential ELN: PJK03-0013PK 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 0 250 500 750 1000 1250 1500 1750 2000 2250 2500 2750 3000 3250 3500 Time (days) T u m o r v o l u m e ( M e d i a n ± Q u a r t i l e ; m m 3 ) **Data: TV (mm3) - 100 + 150 mpk - IMM-1-104
Slide 18: Pancreatic: Comparison with Sotorasib in KRAS-G12C Model
Pancreatic: Head - to - Head Comparison of IMM - 1 - 104 +/ - Sotorasib in a KRAS - G12C Pancreatic Tumor Model MIA PaCa - 2 (KRAS G12C ) Pancreatic Xenograft Tumor Model in Athymic Nude Mice Sotorasib was commercially purchased Tumor Growth Inhibition (TGI) % = [1 – (T i – T 0 )/(C i – C 0 )]x100%;
Slide 19: Pancreatic: Comparison with Sotorasib and Adagrasib in KRAS-G12V Model
Pancreatic: Head - to - Head Comparison of IMM - 1 - 104 vs. Sotorasib and Adagrasib in a KRAS - G12V Pancreatic Tumor Model IMM - 1 - 104 demonstrated tumor regression as compared to no reduction with sotorasib or adagrasib , with insignificant BWL 19 Adagrasib (30, 100 mg/kg QD p.o.) IMM - 1 - 104
Slide 20: Melanoma: Phase 3 NEMO Study
Dummer, et al 2017 Lancet S1470 - 2045 (17) 30180 - 8 2.8 months 1.5 months 11.0 months 10.1 months Binimetinib Dacarbazine Hazard Ratio Progression Free Survival Overall Survival 0.62 1.00 NRAS Status Binimetinib Dacarbazine N = 269 N = 133 Q61K 100 (37%) 51 (38%) Q61L 32 (12%) 17 (13%) Q61R 137 (5
Slide 21: Melanoma: NRAS-Q61R Xenograft vs. Binimetinib
Melanoma: Head - to - Head NRAS - Q61R Melanoma Xenograft Study: Binimetinib vs. IMM - 1 - 104 in SK - MEL - 2 IMM - 1 - 104 as compared to binimetinib monotherapy demonstrated greater tumor growth inhibition (TGI) SK - MEL - 2 (NRAS - Q61R) Melanoma Xenograft Tumor Model in Athymic Nude Mice CRAF -
Slide 22: CRC: Comparison with Selumetinib and Binimetinib
CRC: Head - to - Head Comparison of IMM - 1 - 104 Against Selumetinib and Binimetinib in a KRAS - G12D CRC Syngeneic Mouse Tumor Model 0 3 6 9 12 15 18 21 24 27 0 250 500 750 1000 1250 1500 1750 2000 2250 2500 Time (days) T u m o r v o l u m e ( M e d i a n ± Q u a r t i l e ; m m 3 ) Data: TV (mm3)
Slide 23: IMM-6-415
IMM-6-415 @ Immuneering
Slide 24: IMM-6-415: Monotherapy Activity in RAF and RAS Mutant Tumors
IMM - 6 - 415: Monotherapy Activity in RAF and RAS Mutant Tumors Colon - 26 A - 549 SK - MEL - 2 A - 375 KRAS G12S NSCLC KRAS G12D CRC NRAS Q61R MEL BRAF V600E MEL CRC = colorectal cancer; NSCLC = non - small cell lung cancer; MEL = melanoma SITC 2022 Presentation: Maximum Effective Dose Range in Mi
Slide 25: Enhanced Activity of Checkpoint Inhibitors
Accelerated Cadence of IMM - 6 - 415 Enhanced Activity of Checkpoint Inhibitors Cyclic disruption of MEK improved overall survival with check point inhibitors (SITC 2022) 25 Schedule Dose (mg/kg) Veh ⍺ PD - 1 (BIW) ⍺ CTLA - 4 (BIW) IMM - 6 - 415 IMM - 6 - 415 + PD - 1 IMM - 6 - 415 + CTLA - 4 BID 12
Slide 26: Corporate
Corporate @ Immuneering
Slide 27: Finance & Intellectual Property
• Preliminary estimated Cash, cash equivalents and marketable securities as of March 31, 2023: $91.5M* • Cash runway projected into Q4 2024 supports: • IMM - 1 - 104: • Multiple data readouts from Phase 1/2a trial • IMM - 6 - 415: • Anticipate IND filing in Q4 2023 • Research in additional oncology
Slide 28: Milestones
28 Milestones Program Milestone Expected Timing IMM - 1 - 104 Initial Phase 1 pharmacokinetic (PK) and safety data COMPLETE IMM - 1 - 104 Initial Phase 1 pharmacodynamic (PD) modeling data and additional PK and safety data COMPLETE IMM - 1 - 104 Additional trial updates On a periodic basis IMM - 1 -
Slide 29: Differentiated Approach
Differentiated Approach • Targeting Universal - RAS patient population versus limited single mutation targeted approaches • Once - Daily Oral Dosing • Deep cyclic inhibition targeted, based on: • Manyfold higher C MAX • and short half - life • Approach designed to spare healthy cells and potential t
Slide 30: Appendix
Appendix Nasdaq: IMRX April 2023
Slide 31: Our Platform Converts Gene Expression to Counterintuitive Insights
Our Platform Converts Gene Expression to Counterintuitive Insights Goal: achieve broader activity and better tolerability in RAS and beyond mutant disease Disease Cancellation Disease Amplification Disease Cancellation Disease Amplification 1 st generation MEKi 1 st generation MEKi IMRX Disease Canc
Slide 32: Deep Cyclic Inhibition Demonstrated Using Transcriptomics
Deep Cyclic Inhibition Demonstrated Using Transcriptomics Traditional Approach Signaling Dynamics Chronic Suppression → TOXICITY Cyclic Disruption → TOLERABILITY 32 Syngeneic Colon - 26 study (18 days BID dosing; tumor RNA) Syngeneic Colon - 26 study (18 days BID dosing; tumor RNA)
Slide 33: Dual-MEK Inhibitor
IMM - 1 - 104 is a Dual - MEK Inhibitor Goal deep, cyclic inhibition with ability to prevent MEK - reactivation (improve tolerability and activity) Short plasma half - life to minimize drug trough (~ 1 to 2 hours t 1/2 ) Resists CRAF - bypass in RAS mutant tumors (↓ pERK and pMEK) Ideal Dosing Sched
Slide 34: Comparison Against FDA-Approved MEK Inhibitors: CRAF-Bypass Resistance
Head - to - Head Comparison of IMM - 1 - 104 Against FDA - Approved MEK Inhibitors: CRAF - Bypass Resistance FDA - Approved MEK inhibitors: Trametinib, Cobimetinib, Binimetinib, Selumetinib commercially purchased 1.00 0.03 0.19 0.17 0.21 0.29 1.00 1.24 6.46 2.96 2.45 0.56 0.01 0.10 1.00 10.00 0.1% D
Slide 35: Comparison Against Binimetinib +/- Encorafenib in KRAS-G12S NSCLC
Head - to - Head Comparison of IMM - 1 - 104 Against Binimetinib +/ - Encorafenib in KRAS - G12S NSCLC Tumor Model A549 (KRAS G12S ) NSCLC Xenograft Tumor Model in Athymic Nude Mice Tumor Growth Inhibition (TGI) % = [1 – ( T i – T 0 )/(C i – C 0 )]x100%; Expanded TGI formula vs. previous 1 - [T/C]x1
Slide 36: Comparison Against Binimetinib +/- Encorafenib in BRAF-V600E Melanoma
Head - to - Head Comparison of IMM - 1 - 104 versus Binimetinib +/ - Encorafenib in BRAF - V600E Melanoma Tumor Model A375 (BRAF V600E ) Melanoma Xenograft Tumor Model in Athymic Nude Mice Tumor Growth Inhibition (TGI) % = [1 – ( T i – T 0 )/(C i – C 0 )]x100%; Expanded TGI formula vs. previous 1 -
Slide 37: Conclusions (NRAS mutant Melanoma)
Conclusions (NRAS mutant Melanoma) In the phase 3 NEMO study published in Lancet (c. 2017), binimetinib failed to substantially improve overall survival vs. dacarbazine (11.0 vs. 10.1 months) in NRAS mutant melanoma patients and led to a ~50% increase in serious adverse events (34% vs. 22%). The mos
Slide 38: RAS Mutation Profiles Within Select Tumor Indications
38 RAS Mutation Profiles Within Select Tumor Indications • Based on given tumor type of patients with RAS - mutated tumors in the AACR GENIE database, v13.0 • Each RAS paralogue shown as percent overall RAS mutant tumors within each indication • Presented at 2023 AACR: Targeting RAS. Kolitz, et al.
Slide 39: KRAS Mutant Pancreatic: Translational Opportunity
KRAS Mutant Pancreatic (PAAD): Translational Opportunity GENIE cohort v13.0 - public The AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine Through An International Consortium, Cance r D iscov. 2017 Aug;7(8):818 - 831 ↑ Resistance Mixed Sensitive Have Altered KRAS: Biomar
Slide 40: NRAS Mutant Melanoma: Translational Opportunity
NRAS Mutant Melanoma: Translational Opportunity ↑ Resistance Mixed Sensitive Have Altered NRAS: Biomarker Positive Biomarker Sensitive Profile (19% overall) Biomarker Resistant Profile (0.8% overall) † Further Biomarker Stratification Not Required † MELANOMA Patients GENIE cohort v13.0 - public The
Slide 41: KRAS Mutant NSCLC: Translational Opportunity
KRAS Mutant NSCLC (Adeno): Translational Opportunity Have Altered KRAS: Biomarker Positive Biomarker Sensitive Profile (21.5% overall) Biomarker Resistant Profile (Refine Subsets) NSCLC - Ad Patients † ↑ Resistance (Further Refine Subsets) Sensitive † Consider Further Biomarker Stratification GENIE
Slide 42: KRAS Mutant CRC: Translational Opportunity
KRAS Mutant CRC: Translational Opportunity Have Altered KRAS: Biomarker Positive Biomarker Sensitive Profile (9.3% overall) Biomarker Resistant Profile (Refine Subsets) CRC Patients † ↑ Resistance (Further Refine Subsets) Sensitive † Further Refine Biomarker Stratification GENIE cohort v13.0 - publi
Slide 43: Translating Universal-RAS Potential (AACR GENIE)
Translating IMM - 1 - 104’s Universal - RAS Potential (AACR GENIE ® ) 43 Nair, et al. 2023, AACR: National Meeting, Orlando, FL MAPK + = GENIE patients per indication with activation mutation in KRAS, NRAS, HRAS, BRAF (class I or II), based on 3D - TGA PGx Modeling 0$3.0XWDWHG 1 0$3.:7 1 3$$' 1XPEHU
Slide 44: Translating Universal-RAS Potential (AACR GENIE)
Translating IMM - 1 - 104’s Universal - RAS Potential (AACR GENIE ® ) 44 Nair, et al. 2023, AACR: National Meeting, Orlando, FL MAPK + = GENIE patients per indication with activation mutation in KRAS, NRAS, HRAS, BRAF (class I or II), based on 3D - TGA PGx Modeling For 122 3 D - TGA cell lines where
Slide 45: Translating Universal-RAS Potential (AACR GENIE)
Translating IMM - 1 - 104’s Universal - RAS Potential (AACR GENIE ® ) 45 Nair, et al. 2023, AACR: National Meeting, Orlando, FL MAPK + = GENIE patients per indication with activation mutation in KRAS, NRAS, HRAS, BRAF (class I or II), based on 3D - TGA PGx Modeling For 122 3 D - TGA cell lines where
Slide 46: Translating Universal-RAS Potential (AACR GENIE)
Translating IMM - 1 - 104’s Universal - RAS Potential (AACR GENIE ® ) 46 Nair, et al. 2023, AACR: National Meeting, Orlando, FL MAPK + = GENIE patients per indication with activation mutation in KRAS, NRAS, HRAS, BRAF (class I or II), based on 3D - TGA PGx Modeling For 122 3 D - TGA cell lines where
Slide 47: Translating Universal-RAS Potential (AACR GENIE)
Translating IMM - 1 - 104’s Universal - RAS Potential (AACR GENIE ® ) 47 Nair, et al. 2023, AACR: National Meeting, Orlando, FL MAPK + = GENIE patients per indication with activation mutation in KRAS, NRAS, HRAS, BRAF (class I or II), based on 3D - TGA PGx Modeling For 122 3 D - TGA cell lines where