Immuneering Corporation · NASDAQ:IMRX
Immuneering — Investor Presentation (March 2023)
39 slides from Immuneering's investor presentation, Mar 6, 2023
Slide 1: Building a Universal-RAS Franchise
Building a Universal-RAS Franchise Nasdaq: IMRX With the potential to benefit more than 1.5 million cancer MARCH 2023 patients
Slide 2: Forward-looking statements
2 2023 Corporate Presentation 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 statemen
Slide 3: Our approach is different; Investment Summary
“Our approach is different.” • Targeting large Universal-RAS patient population (1.5M) versus more limited approaches. • Monotherapy vs combination therapy potential • Deep cyclic inhibition achieved briefly but forcefully, due to combination of: • Manyfold higher CMAX • and short half life • Approa
Slide 4: IMM-1-104's Potential … Universal-RAS
4 2023 Corporate Presentation IMM-1-104’s Potential … Universal-RAS NRAS (14.12%) Targeted KRASG12C • 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 paralogue • Select mutation percentages wit
Slide 5: MoA Target Engagement: Deep, Cyclic Inhibition
5 2023 Corporate Presentation MoA Target Engagement Prevent MAPK -pathway bypass events GOAL: Expanded activity into RAS mutant setting Near -Zero Drug Trough Short plasma half -life GOAL: Improve tolerability and limit adaptive resistance: every day is a drug holiday Dramatic PK CMAX Pulse Many fol
Slide 6: Development Pipeline
PROGRAM INDICATION DISCOVERY IND-ENABLING PHASE 1 PHASE 2 PHASE 3 MILESTONE IMM-1-104 Universal-RAS Phase 1/2a Trial Enrolling; initial PK and safety data expected mid-2023 IMM-6-415 Universal-MAPK IND filing in Q4 2023 Multiple additional programs in discovery phase Development Pipeline 6 Cash, cas
Slide 7: IMM-1-104
IMM-1-104 II
Slide 8: IMM-1-104
8 2023 Corporate Presentation IMM-1-104 ➢ 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-c
Slide 9: IMM-1-104 Demonstrates Universal-RAS Potential
IMM-1-104 Demonstrates Universal-RAS Potential 9 2023 Corporate Presentation 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
Slide 10: IMM-1-104 Demonstrates Universal-RAS Potential
IMM-1-104 Demonstrates 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) Tu m o r v olu m e (M e dia n ± Q u artile; m m 3 ) **Data: TV (mm3) - 100 + 150 mpk - IMM-1-104 MEDIAN Vehicle 0
Slide 11: Pancreatic: Head-to-Head Comparison of IMM-1-104 +/- 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 (KRASG12C) Pancreatic Xenograft Tumor Model in Athymic Nude Mice Sotorasib was commercially purchased Tumor Growth Inhibition (TGI) % = [1 – (Ti – T0 )/(Ci – C0 )]x100%; Expanded TGI formu
Slide 12: Pancreatic: Head-to-Head Comparison vs. 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 sotorasib or adagrasib, with insignificant BWL 12 2023 Corporate Presentation Adagrasib (30, 100 mg/kg QD p.o.) IMM-1-104 (100, 15
Slide 13: Melanoma: Phase 3 NEMO Study: Binimetinib vs. Dacarbazine
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 (51%)
Slide 14: Melanoma: Head-to-Head NRAS-Q61R Xenograft Study: Binimetinib vs. IMM-1-104
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-bypass IMM-1-104 (100-125
Slide 15: CRC: Head-to-Head Comparison Against 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) Tumor volume (Median ± Quartile; mm3 ) Data: TV (mm3) - Selumetinib - 50 only Vehicle 0
Slide 16: IMM-1-104: 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 Study 1 First Time in Humans RP2D May expand tolerated dose cohorts for a max of 42
Slide 17: Phase 1/2a Study of IMM-1-104 Trial Sites
17 Phase 1 Sites A Phase 1/2a Study of IMM-1-104 in Participants With Previously Treated, RAS-Mutant, Advanced or Metastatic Solid Tumors ClinicalTrials.gov Identifier: NCT05585320 MD Anderson Cancer Center › Houston, Texas, United States, 77030 › Principal Investigator: Shubham Pant, MD United Stat
Slide 18: Upcoming Potential Milestones
18 2023 Corporate Presentation Upcoming Potential Milestones Program Milestone Expected Timing IMM-1-104 Initial Phase 1 pharmacokinetic (PK) and safety data Mid-2023 IMM-1-104 Initial Phase 1 pharmacodynamic (PD) modeling data and additional PK and safety data 2H 2023 IMM-1-104 RP2D and Safety data
Slide 19: IMM-6-415
IMM-6-415
Slide 20: IMM-6-415: Monotherapy Activity in RAF and RAS Mutant Tumors
IMM-6-415: Monotherapy Activity in RAF and RAS Mutant Tumors SK-MEL-2 A-375 A-549 Colon-26 KRASG12S NSCLC KRASG12D CRC NRASQ61R MEL BRAFV600E MEL SITC 2022 Presentation: Maximum Effective Dose Range in Mice (plasma t CRC = colorectal cancer; NSCLC = non-small cell lung cancer; MEL = melanoma 1/2 = 0
Slide 21: Accelerated Cadence of IMM-6-415 Enhances Activity of Checkpoint Inhibitors
Accelerated Cadence of IMM-6-415 Enhances Activity of Checkpoint Inhibitors Cyclic disruption of MEK improves overall survival with check point inhibitors (SITC 2022) 21 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 120 0/12 7/12 11/12 10/12 BI
Slide 22: Corporate
Corporate II
Slide 23: Finance & Intellectual Property
• Cash, cash equivalents and marketable securities as of December 31, 2022: $105.5M • Cash runway 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 programs 23 2023 Corporate Presentati
Slide 24: Our approach is different; Investment Summary
“Our approach is different.” • Targeting large Universal-RAS patient population (1.5M) versus more limited approaches. • Monotherapy vs combination therapy potential • Deep cyclic inhibition achieved briefly but forcefully, due to combination of: • Manyfold higher CMAX and • short half life • Approa
Slide 25: Appendix
Appendix Nasdaq: IMRX March 2023
Slide 26: Differentiation Versus Other MEK Inhibitors
Differentiation Versus Other MEK Inhibitors 1 st Gen Mechanism Potentially Susceptible to CRAF-bypass Potential Short PK Exposure (Improve Tolerability & Durability) Potential Chronic Exposure (Drug Toxicity) 2 nd Gen Mechanism Potentially Resistant to CRAF-bypass BAY-265 VS-6766 Trametinib Cobimeti
Slide 27: 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 28: Deep Cyclic Inhibition Confirmed Using Transcriptomics
Deep Cyclic Inhibition Confirmed Using Transcriptomics Traditional Approach Signaling Dynamics Chronic Suppression → TOXICITY Cyclic Disruption → TOLERABILITY 28 Syngeneic Colon-26 study (18 days BID dosing; tumor RNA) Syngeneic Colon-26 study (18 days BID dosing; tumor RNA) 2023 Corporate Presentat
Slide 29: IMM-1-104 is a 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 t1/2) Resists CRAF-bypass in RAS mutant tumors (↓ pERK and pMEK) Ideal Dosing Schedule: ≥ 7-8 hal
Slide 30: 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% DMSO T rametini
Slide 31: Head-to-Head Against Binimetinib +/- Encorafenib in KRAS-G12S NSCLC Model
Head-to-Head Comparison of IMM-1-104 Against Binimetinib +/- Encorafenib in KRAS-G12S NSCLC Tumor Model A549 (KRASG12S) NSCLC Xenograft Tumor Model in Athymic Nude Mice Tumor Growth Inhibition (TGI) % = [1 – (Ti – T0 )/(Ci – C0 )]x100%; Expanded TGI formula vs. previous 1-[T/C]x100% method Human Dos
Slide 32: Head-to-Head Against Binimetinib +/- Encorafenib in BRAF-V600E Melanoma Model
Head-to-Head Comparison of IMM-1-104 versus Binimetinib +/- Encorafenib in BRAF-V600E Melanoma Tumor Model A375 (BRAFV600E) Melanoma Xenograft Tumor Model in Athymic Nude Mice Tumor Growth Inhibition (TGI) % = [1 – (Ti – T0 )/(Ci – C0 )]x100%; Expanded TGI formula vs. previous 1-[T/C]x100% method Hu
Slide 33: 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 34: RAS Mutation Profiles Within Select Tumor Indications
34 2023 Corporate Presentation 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: Targ
Slide 35: KRAS Mutant Pancreatic (PAAD): Translational Opportunity
35 2023 Corporate Presentation I 35 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, Cancer Discov. 2017 Aug;7(8):818-831 Sensitive Mixed ↑ Resist
Slide 36: NRAS Mutant Melanoma: Translational Opportunity
36 2023 Corporate Presentation I 36 NRAS Mutant Melanoma: Translational Opportunity Sensitive Mixed ↑ Resistance Have Altered NRAS: Biomarker Positive Biomarker Sensitive Profile (19% overall) Biomarker Resistant Profile (0.8% overall) † Further Biomarker Stratification Not Required † MELANOMA Patie
Slide 37: KRAS Mutant NSCLC (Adeno): Translational Opportunity
37 2023 Corporate Presentation I 37 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 † Sensitive ↑ Resistance (Further Refine Subsets) † Consider Furth
Slide 38: KRAS Mutant CRC: Translational Opportunity
38 2023 Corporate Presentation I 38 KRAS Mutant CRC: Translational Opportunity Have Altered KRAS: Biomarker Positive Biomarker Sensitive Profile (9.3% overall) CRC Biomarker Resistant Profile (Refine Subsets) Patients † Sensitive ↑ Resistance (Further Refine Subsets) † Further Refine Biomarker Strat
Slide 39: Phase 1/2a Primary and Secondary Outcomes
Safety • Adverse Events (AEs) 39 2023 Corporate Presentation Dose-limiting Toxicities Recommended Phase 2 Dose • Selection of dose candidate • Number of participants with dose limiting toxicities Phase 1/2a Primary and Secondary Outcomes Phase 1: Primary Outcomes Phase 1/2a: Secondary Outcomes CMAX