EX-99.2 3 brhc10046437_ex99-2.htm EXHIBIT 99.2
Exhibit 99.2

 Transformative Medicines for Patients  January 2023 
 

 This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “can,” “will,” “believe,” “expect,” “plan,” “anticipate,” “potential” and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this presentation are forward-looking statements. These statements include, but are not limited to, statements regarding the marketing, therapeutic potential, and expected clinical benefits, including extended overall survival benefit and reduction in circulating tumor DNA, of Immunocore’s products and product candidates; expectations regarding the development of Immunocore’s pipeline and the design, progress, timing, enrollment, scope, expansion and results of Immunocore’s existing, planned and other future clinical trials and IND enabling studies, including the targeted delivery of IND for three new product candidates, the expansion of, and timing for reporting data from the monotherapy and combination arms of, the PRAME-A02 trial and the timing for reporting data from the single ascending dose portion of the IMC-M113V Phase 1 HIV clinical trial; the ability of TCR therapeutics to target 90% of the human proteome; statements regarding the durability, efficacy and toleration of Immunocore’s product candidates; expectations regarding the commercialization of KIMMTRAK including potential growth opportunities and trends and increasing access to KIMMTRAK; expectations regarding the value proposition of KIMMTRAK in metastatic uveal melanoma (mUM) and advanced melanoma; expectations regarding the potential market size and opportunity for Immunocore’s products and product candidates, including statements with respect to potential patient population; expectations regarding the potential of PRAME-A02 to benefit a large number of patients; the Company’s belief that IMC-R117C is potentially the first-in-class PIWIL1-targeted immunotherapy for colorectal and other gastrointestinal cancers; statements regarding the planned IND timing for IMC-R117C; expectations regarding future milestones; future development plans of tebentafusp and Immunocore’s other product candidates; the ability to obtain and maintain regulatory approval for its products and product candidates; expectations regarding the sustained or potential commercial performance and uptake of KIMMTRAK and Immunocore’s other product candidates, if approved; expectations regarding Immunocore’s management of resources and expected cash runway; and preliminary unaudited net sales and cash and cash equivalents of KIMMTRAK and tebentafusp; and the validation of the ImmTAC platform.   These forward-looking statements are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially and adversely from those expressed or implied by any forward-looking statements, many of which are beyond Immunocore’s control. These include, without limitation, risks and uncertainties related to the impact of worsening macroeconomic conditions and the ongoing and evolving COVID-19 pandemic, the war in Ukraine or global geopolitical tension on Immunocore’s business, strategy, clinical trials, financial position and anticipated milestones, including Immunocore’s ability to conduct ongoing and planned clinical trials; Immunocore’s ability to obtain and maintain regulatory approval of its product candidates; Immunocore’s ability to obtain clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products, including as a result of supply chain disruptions; Immunocore’s ability to develop, manufacture and commercialize its product candidates; Immunocore’s ability and plans to launch, market and sell KIMMTRAK or any future approved products, to continue to establish and expand a commercial infrastructure; Immunocore’s ability to successfully expand the approved indications for KIMMTRAK, or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to the COVID-19 pandemic, patient enrollment delays or otherwise; unexpected safety or efficacy data observed during preclinical studies or clinical trials and Immunocore’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any product candidates it is developing; clinical trial site activation or enrollment rates that are lower than expected; Immunocore’s need for and ability to obtain additional funding on favorable terms or at all, including as a result of worsening macroeconomic conditions such as rising inflation and interest rates, volatility in the capital markets and related market uncertainty; and the success of Immunocore’s current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section titled ‘Risk Factors’; in Immunocore’s filings with the Securities and Exchange Commission, including Immunocore’s most recent Annual Report on Form 20-F, as supplemented by its most recent filings that Immunocore has made or may make with the SEC in the future. Such risks may be amplified by the COVID-19 pandemic and its potential impact on Immunocore’s business and the overall global economy. Any forward-looking statements represent Immunocore’s views only as of the date of this presentation and should not be relied upon as representing its views as of any subsequent date. Immunocore does not assume any obligation to update any forward-looking statements, except as may be required by law. In addition, as the reported net sales and cash and cash equivalents in this presentation are preliminary, have not been audited and are subject to change pending completion of our audited financial statements for the year ended December 31, 2022, it is possible that Immunocore or its independent registered public accounting firm may identify items that require Immunocore to make adjustments to the amount included in this presentation, and such changes could be material. Additional information and disclosures would also be required for a more complete understanding of Immunocore’s financial position and results of operations as of December 31, 2022.   Certain information contained in this presentation relates to or is based on studies, publications, surveys, and other data obtained from third-party sources and Immunocore’s own internal estimates and research. While Immunocore believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy, or completeness of, any information obtained from third-party sources.  KIMMTRAK™ is a trademark owned or licensed to Immunocore.  Forward-looking statement  2 
 

 We have written the next chapter in cancer treatment  3  T Cell Receptor (TCR) Therapy   Off-the-shelf bispecific T cell engagers  Chemotherapy  1949   Targeted Therapy  1997   Immunotherapy  2011   Antibody-DrugConjugate  2013   Cell Therapy  2017   2022  
 

 4  Harnessing the immune system to fight disease with targeted, off-the-shelf, bispecific, soluble T cell receptors (TCRs) 
 

 5  Multiple candidates in oncology and infectious diseases  Delivering leading bispecific TCR pipeline  Candidate  Target  Indication  IND-enabling  Phase 1  Phase 2  Phase 3  Approved  gp100  Uveal melanoma  Tebentafusp  Advanced melanoma  IMC-F106C  PRAME-A02  Multiple solid tumors   Multiple solid tumors  2L+ cutaneous melanoma  PRR Ovarian*  Advanced endometrial  2L+ NSCLC  IMC-P115C  PRAME-A02-HLE  Multiple solid tumors  IMC-T119C  PRAME-A24  Multiple solid tumors  IMC-R117C  PIWIL1  Colorectal, gastric, pancreatic  IMC-C103C1  MAGE-A4  Multiple solid tumors  IMC-I109V  Envelope  Hepatitis B Virus (HBV)  IMC-M113V2  Gag  Human Immunodeficiency Virus (HIV)  ONCOLOGY  INFECTIOUS DISEASES  Monotherapy dose exploration  Combinations w/ standards of care   New ImmTAC candidate  1. Developed under a co-development/co-promotion collaboration with Genentech; 2. Program is wholly owned, development costs being provided by the Bill & Melinda Gates Foundation (BMGF), Immunocore retains all development and commercialization rights in the developed world. * Platinum refractory or resistant serous ovarian carcinoma 
 

 Technology platform 
 

 7  …into soluble, off-the-shelf, bispecific therapeutics (ImmTAX)  We pioneered converting membrane-bound T cell receptors…  Natural TCR  ImmTAX 
 

 8  TCR therapeutics target >90% of the human proteome 
 

 Our platform is modular  Applicable across 3 therapeutic areas  9  Oncology  Infectious Diseases  Autoimmune Conditions  UPREGULATION OF THE IMMUNE SYSTEM  DOWNREGULATION OF THE IMMUNE SYSTEM 
 

 KIMMTRAK® in metastatic melanoma 
 

 11  We are using our TCR technology to target gp100 protein in melanoma  Metastatic Uveal Melanoma (mUM): is an ultra-rare and aggressive tumor  ~1,000  Until KIMMTRAK,   no approved treatment3  Originates from melanocytes within the uveal tract of the eye  Median age at diagnosis is 62 years1  HLA-02 mUM pts per year in the US/EU2  Up to 50%  may develop metastatic disease; liver primary site of metastasis1  Historic median survival with metastatic disease2  ~12 months  1. Yang J et al. Ther Adv Med Oncol. 2018 ; 2. Carvajal RD et al. Br J Ophthalmol. 2017; 3. Rantala ES et al. Melanoma Res. Published online. 2019 
 

 Nathan, P. et. al. New England Journal of Medicine 2021; 385:1196-1206  12  KIMMTRAK®: First-in-class, off-the-shelf, bispecific TCR  Primary endpoint: Overall Survival (OS) statistically significant  Overall Survival benefit in patients treated with KIMMTRAK or investigator’s choice in first-line  KIMMTRAK was proven to extend median OS by 6 months  months median OS  hazard ratio  21.7  0.51 
 

 Safety profile of KIMMTRAK was predictable and manageable  13  Key KIMMTRAK findings  No treatment related deaths  378 previously untreated mUM patients randomized 2:1 KIMMTRAK vs. Investigator’s Choice (pembrolizumab 82%, ipilimumab 13%, dacarbazine 6%)  Majority of ARs in first 3 weeks  Low discontinuation rate: KIMMTRAK 2% vs. Investigator’s Choice of 4.5%  Adverse Reactions (AR)  Any Grade, %  Grade 3 or 4, %  Any  244 (99.6)  110 (45)  Cytokine release syndromea  89  0.8  Rashb  83  18.4  Pyrexia  76  3.7  Pruritus  69  4.5  Fatigueb  64  5.7  Nausea  49  2  Chills  48  0.4  Hypo-/hyperpigmentationb  47  0.4  Abdominal painb  45  2.9  Edemab  45  0  Adverse Reactions (ARs) consistent with mechanism of action  KIMMTRAK (n = 245)*  * KIMMTRAK. US Package insert. Immunocore Ltd.; 2021. Adverse reactions listed are those with any grade >45%; a. Represents algorithmic identification of CRS cases based on ASTCT grading criteria (Lee et al. 2019). b. Represents a composite of multiple related terms. 
 

 Time since last dose of prior anti-PD(L)1 does not impact OS  14  OS by whether prior anti-PD(L)1 therapy was remote or most recent therapy  Tebentafusp active in cutaneous melanoma  Time from prior anti-PD(L)1  1-yr OS  2-yr OS  Remote  75%  22%  Immediately prior  75%  23%  Benchmark  55%   N/A  Median time from last anti-PD(L)1 to tebentafusp  2-yr OS  Remote anti-PD(L)1  9 months  Anti-PD(L)1 immediately prior  2 months  Remote = Patients received prior anti-PD1 but it was not most recent therapy prior to enrolment  Immediately prior = anti-PD1 was most recent therapy prior to enrolment  Middleton et al., ASCO 2022 
 

 15  Randomization to ‘real world’ treatment as a control arm  Phase 2/3 trial for previously treated, advanced melanoma patients  Phase  Primary endpoint  Per arm size  2  ctDNA and OS  40  3  OS  170  Optionality to review Phase 2 data to inform changes to Phase 3, including line of prior therapy, dropping an Arm and optimize powering of study   Investigator discretion on subsequent therapy: local standard, supportive care or other clinical trials.  Collect data on subsequent therapy, survival and ctDNA sample.  HLA*A2:01  Advanced melanoma  Uveal melanoma excluded  Prior anti-PD(L)1  Progression within 6 months last dose   Prior ipilimumab   Prior TKI (BRAFm)  1:1:1 Randomization   Treatment phase  OS follow-up  Tebentafusp  Tebentafusp + anti-PD-1  R  Straight to follow-up 
 

 PRAME Franchise:A02, A24, A02-HLE  
 

 PRAME heavily expressed in multiple solid tumor types  LOW  HIGH  Tumor  gp100 expression  PRAME  expression  MAGE-A4 expression  Cutaneous melanoma  Renal Cell Carcinoma (RCC)  Bladder  Non-Small Cell Lung Cancer (NSCLC)  Hepatocellular carcinoma (HCC)  Gastric   Esophageal  SCCHN1  Small Cell Lung Cancer (SCLC)  Triple Negative Breast Cancer (TNBC)  Endometrial  Cervical  Ovarian  Uveal melanoma  Relative Checkpoint Inhibitor sensitivity  17  Epidemiology data from cancer registries and Decision Resources, Annual incidence of metastatic patients; 1. Squamous cell carcinoma of head and neck cancer 
 

 18  Most broadly expressed cancer-testis antigen in several tumor types but with minimal normal tissue expression  IMC-F106C: ImmTAC targeting HLA-A2-presented peptide from PRAME  Squamous NSCLC  Adeno NSCLC  Ovarian serous carcinoma  Cutaneous melanoma  Endometrial adenocarcinoma 
 

 IMC-F106C-101 PRAME Phase 1 study design  19  Screening  Treatment  Follow-up  Weekly IV infusion with intra-patient dose escalation (over 3 weeks)  Tumor assessment every 9 weeks  HLA-A*02:01 (central testing)  Select advanced solid tumors  Tumor PRAME by immunohistochemistry  High PRAME prevalence: enroll all comers; test retrospectively  All other indications: prospective confirmation of PRAME  Key eligibility criteria  Primary endpoint  Determine MTD/expansion dose  Secondary endpoint  Preliminary antitumor activity  Pharmacokinetics   Pharmacodynamic markers  Key objectives  Dose Escalation  Target Dose,   Starting Day 15  0.3-10 mcg  20 mcg  40 mcg  80 mcg  160 mcg  320 mcg  Total safety population N = 55  Cohorts 1-5  Cohorts 6 and above  Efficacy population   n=31*  Strong and consistent pharmacodynamic activity  * Of 36 patients treated at target escalation dose of ≥20 mcg, 5 patients were excluded from efficacy analyses as they were PRAME-negative (n=2) or not yet had tumor assessment (n=3) 
 

 20  T cell activation and re-direction into tumor seen across ImmTAC platform  Strong and consistent pharmacodynamic activity at ≥20 mcg IMC-F106C  Interferon induction  T cell trafficking  Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355. 
 

 Baseline patient characteristics  21  Characteristic  Safety Population  N=55  Efficacy Population  N=31†  Age – Mean (range)  60 (26, 79)  61 (36, 79)  ECOG status 0 – n (%)  30 (55%)  19 (61%)  PRAME status (IHC)  Positive  49 (89%)  28 (90%)  Negative  2 (4%)  0  Not evaluable   4 (7%)  3 (10%)  Median H-score  195  188  Tumor type        Melanoma  34 (62%)  17 (55%)  Uveal (UM)  26 (47%)  11 (35%)  Cutaneous (CM)*  8 (15%)  6 (19%)  Ovarian Carcinoma  10 (18%)  5 (16%)  Serous (SOC)*   7 (13%)  4 (13%)  Non-serous  3 (5%)  1 (3%)  NSCLC  4 (7%)  4 (13%)  TNBC*  3 (5%)  3 (10%)  Endometrial*  4 (7%)  2 (6%)  Median PRAME H-score (188) in efficacy population was high  Efficacy population heavily pretreated  Ovarian: all platinum resistant   CM: all received prior anti-PD1 and anti-CTLA4   NSCLC: all received prior anti-PD1  TNBC and endometrial: 2-5 prior lines of therapy  * In efficacy population, these tumors enrolled regardless of PRAME immunohistochemistry (IHC) testing, which was evaluated retrospectively. NSCLC squamous also enrolled regardless of PRAME testing   † Of 36 patients treated at target escalation dose of ≥20 mcg, 5 patients were excluded from efficacy analyses as they were PRAME-negative (n=2) or not yet had tumor assessment (n=3)  Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355. 
 

 Most frequent related AE was Grade 1/2 CRS, consistent with proposed mechanism  IMC-F106C was well tolerated  MTD not reached  CRS events were all manageable  Majority (77%) within first 3 doses   71% Grade 1   29% Grade 2   No Grade ≥ 3 CRS  No treatment-related discontinuation or Grade 5 related AEs  Adverse events attenuate over time  Preferred Term (MedDRA v23.1)  0.3 – 10 mcg†N=18  20 – 320 mcg†N=37  Total  N=55  All grades (events in ≥ 25% of patients), n (%)  At least one event  18 (100)  34 (92)  52 (95)  Pyrexia*  10 (56)  21 (57)  31 (56)  Cytokine release syndrome  5 (28)  22 (59)  27 (49)  Fatigue  6 (33)  13 (35)  19 (35)  Hypotension*  3 (17)  15 (41)  18 (33)  Chills  9 (50)  8 (22)  17 (31)  Nausea  7 (39)  10 (27)  17 (31)  Rash  3 (17)  12 (32)  15 (27)  Grade ≥ 3  (Events in > 1 patient), n (%)   At least one event  6 (33)  13 (35)  19 (35)  Lymphopenia  1 (6)  7 (19)  8 (15)  Aspartate aminotransferase increased  3 (17)  1 (3)  4 (7)  Anemia  1 (6)  2 (5)  3 (5)  Alanine aminotransferase increased  2 (11)  0  2 (4)  Arthralgia  1 (6)  1 (3)  2 (4)  Pyrexia*  0  2 (5)  2 (4)  22  * Includes events reported as a sign/symptom of CRS  † Safety presented by intended target escalation dose on Day 15. 1/37 patients received only a single dose of 2 mcg and did not reach target dose of ≥ 20 mcg  Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355. 
 

 * Two patients (1 with NSCLC, 1 serous ovarian) discontinued treatment due to PD with scan data not available at DCO ; † This serous ovarian patient (H-score 39) had an unconfirmed partial response (uPR) at the time of the ESMO Congress September 2022 presentation, that was subsequently confirmed.; ‡ PRAME expression assessed by IHC H-score; Two PRAME-negative patients both had PD (not shown); Endo, endometrial carcinoma; NSCLC, non small cell lung carcinoma; TNBC, triple-negative breast cancer.  Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355.  23  IMC-F106C ESMO 2022  Responses observed in multiple tumor types  Positive Not evaluable  PRAME expression‡ 
 

 NSCLC, non small cell lung carcinoma  Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355.  24  IMC-F106C ESMO 2022  Majority of patients have durable tumor response or stabilization 
 

 25  IMC-F106C ESMO 2022 | Two PRs ongoing for 7+ months  Responses are durable, 6 of 7 PRs still ongoing  * PRAME expression assessed by IHC H-score  Endo, endometrial carcinoma; NSCLC, non small cell lung carcinoma; TNBC, triple-negative breast cancer; UM, uveal melanoma; ctDNA, circulating tumor DNA; ND, not yet determined (9 patients pending); NE, not evaluable; PR, partial response; Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355. 
 

 † 20 of 31 efficacy evaluable patients had paired ctDNA. Data not yet available for 9 patients, including 3 PRs. Two patients did not have baseline detectable ctDNA.  B, triple-negative breast cancer; C, cutaneous melanoma; ctDNA, circulating tumor DNA; E, endometrial carcinoma; LA, non small cell lung adenocarcinoma; LS, non small cell lung squamous cell carcinoma; O, ovarian; U, uveal melanoma; CPI, checkpoint inhibitor; tebe, tebentafusp.; Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355.  26  IMC-F106C ESMO 2022  Reduction in circulating tumor DNA observed across tumor types  4 PR patients evaluated for ctDNA had > 50% reduction, including 3 with clearance  Two patients had ctDNA clearance despite best response of PD  ctDNA reduction   correlated with OS in KIMMTRAK mUM study 
 

 Monotherapy activity provides optionality to develop   in single arm and randomized trials  27  Expanding clinical trial footprint | Aim to understand breadth of clinical activity in solid tumors   Enrolling patients globally in adaptive trial with multiple arms  P  Endometrial  Monotherapy expansion  Monotherapy IV  dose escalation  Checkpoint inhibitor combinations  ImmTAC   combinations  Chemotherapy combinations  Monotherapy  Combinations   NSCLC  Monotherapy expansion  Ovarian  Monotherapy expansion  Cutaneous melanoma  Monotherapy expansion  Enables future randomized trials into earlier lines of therapy   Adaptive design enables flexible expansion size  
 

 Total ~150,000   PRAME+, HLA-A2 patients/year  PRAME-A02 has the potential to benefit a large number of patients  Tumor type  Prevalence of PRAME expression1  HLA*02:01+, PRAME+ metastatic patients (G7)2  70-100%    Endometrial  >10K  Melanoma  >10K  Ovarian  >15K  NSCLC-squamous  >30K  50-70%  NSCLC-adeno  >40K  SCLC  >15K  TNBC  >5K  20-50%  SCCHN  >30K  Gastric  RCC  Esophageal  Cholangiocarcinoma  Cervical  28  1. PRAME prevalence derived from immunohistochemistry and RTqPCR of patient samples and analysis of TCGA  2. Epidemiology data from cancer registries and Decision Resources, Annual incidence of metastatic patients 
 

 Consistency of RECIST responses enriched at higher H scoresKIMMTRAK demonstrated ctDNA reduction and OS benefit at high and low H score  29  PRAME  MAGE-A4  KIMMTRAK  Phase 1/2  Study IMCgp100-1021  Phase 1  Study IMC-C103C-1012,5,6  Phase 1   Study IMC-F106C-1013,4  Non-PR  PR  Best overall response  1. Carvajal RD, et al. Nat Med 2022 28:2364-2373; 2. Davar D, et al. Ann Oncol 2021 32:S1411-S1413; 3. Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355; Sweis, R. et. al., Ann Oncol 2022 (ESMO I-O 2022); 4. Includes H score negative and positive patients who received ≥ 20 mcg target dose and were efficacy evaluable. Excluded are patients with unevaluable H score and 5 mUM IMC-F106C patients who progressed on prior KIMMTRAK; 5. includes H score negative and positive patients who received ≥ 90 mcg target dose and were efficacy evaluable. 6. One patient (MAGE-A4 H score 265) had an SD convert to an uPR after the data cutoff for the presentation and remains on study as of 05Dec2022. Medians represent all patients. 
 

 30  Consistency of ImmTAC platform beyond gp100  T cell activation  Durable tumor shrinkage  Activity even in low target expression  ctDNA reduction  Overall survival benefit  KIMMTRAK®   gp100   IMC-F106C  PRAME   IMC-C103C  MAGE-A4  
 

 HLE, Half-life extension  Building on enthusiasm for IMC-F106C targeting PRAME HLA-A02  Expansion of ImmTAC franchise targeting PRAME   IMC-F106C  PRAME  HLA-A02   TCRxCD3  Clinically validated   Focus on expanding clinical program  IMC-T119C  PRAME  HLA-A24  TCRxCD3  Expands potential addressable population by ~30% (G7)   High prevalence in Japan  IMC-P115C  PRAME  HLA-A02  TCRxCD3 HLE   Half-life extended (HLE) for less frequent dosing   Target  HLA subtype  Format  31 
 

 32  IND enabling studies ongoing  IMC-P115C: Half-Life Extended (HLE) ImmTAC targeting PRAME-A02  * Half-life estimated using a research tool version of IMC-P115C  Same PRAME peptide  Same CD3 end  Less frequent dosing  Same TCR specificity  Half-life ~ 7 days in mouse PK study*  Highly potent in vitro 
 

 Prevalence of individual HLA subtypes 2. 5EU: France, Germany, Italy, Spain, and the United Kingdom   33  IND enabling studies ongoing  IMC-T119C: ImmTAC targeting PRAME-A24  Patient diversity, including Japan  Expands beyond PRAME-A02 by ~30% in non-overlapping patients  PRAME-A02 development as a blueprint  US  15-20%  ~40%  5EU2  ~20%  ~45%  Japan  ~30%  ~60%  HLA-A*24:02  HLA-A*02:01  S. Korea  ~30%  ~40%  Expands & diversifies patient population1 
 

 Novel ImmTAC Candidate for GI cancers from our discovery engine 
 

 PIWIL1, piwi-like protein1, MSS,   ^ including mutant & wildtype RAS and BRAF; microsatellite stable (MSS) and Microsatellite instability (MSI)-high      35  CRC is historically insensitive to immune checkpoints  PIWIL1: promising target in colorectal cancer (CRC)  PIWIL1 RNA in situ hybridization  Colon adenocarcinoma  Normal colon  PIWIL1 detected   Negative prognostic marker in multiple cancers, involved in tumor progression  25% CRC patients have broad PIWIL1 expression (e.g., > 75% of tumor cells positive)   Expressed in CRC, historically insensitive to IO, and across major subgroups^ 
 

 ImmTAC, Immune mobilizing T cell receptor Against Cancer; PIWIL, piwi-like protein 1  36  IND planned Q4 2023  IMC-R117C: First-in-class immunotherapy targeting PIWIL1 (PIWIL1 x CD3)  Tumor type  Prevalence of PIWIL1 expression  HLA*02:01+, PIWIL1+ metastatic patients (G7)  20-30%  Colorectal  >20K  Esophageal  >xK  15-20%  Ovarian  ~10K  Gastric  >xK  ~10-15%  Endometroid  ~6K  Pancreatic  >xK  Total >35,000   PIWIL1+, HLA-A2 patients/year  Relative PIWIL1 expression  PIWIL RNA expression   Individual patient tumor  n = mRNA sample size 
 

 Pursuing a functional cure in infectious diseases 
 

 Our unique approach for functional cure of chronic Hepatitis B  Key advantages of redirecting non-exhausted T cells  Same CD3 MoA validated in oncology  Independent of natural T cell reactivity to Hep B  Goal is functional cure with finite treatment  Mass-spectrometry antigen discovery engine for HBV  Pipeline funnel (e.g., conserved sequences, pHLA presentation/stability, mimetic risk)  Seven optimal targets identified from envelope, core capsid, and polymerase  38 
 

 IMC-I109V:  Encouraging signs of activity observed in HBV  39  Induction of IL-6 in all 3 patients1  Transient decrease in HBsAg transiently coincided   with transient increase in ALT 1  Patient #1  Patient #2  Patient #3  1. Bourgeois, et al. EASL 2022  Initial results from single 0.8 mcg dose presented at EASL 2022 
 

 40  Functional cure program for HIV with goal of eliminating HIV reservoirs  Same MoA as tebentafusp, but optimized for low target viral peptide presentation   Bypasses exhausted T cells  Targets highly conserved & functionally constrained viral epitopes  Active in ex vivo assays of infected CD4+ T cells from ART-treated HIV patients  Soluble format access to tissue reservoirs  Initial IMC-M113V Phase 1 data in 2023 
 

 KIMMTRAK commercial performance 
 

 ~$400M  *Preliminary financial results are approximated and unaudited. 1. “Net sales” refers to total net product and net pre-product revenue of KIMMTRAK and tebentafusp. 2. Dollar amounts based on conversion rate of approximately 1.21.   42  ~$50M  Q4 preliminary net sales of KIMMTRAK / tebentafusp1,2  Preliminary cash and cash equivalents as of December 31, 20222  YE preliminary net sales of KIMMTRAK / tebentafusp1,2  Cash runway projected into 2026 with anticipated KIMMTRAK revenues  ~$140M  Preliminary 2022 Financial Results 
 

 Delivering on our promise – Consistent execution 
 

 41st Annual J.P. Morgan Healthcare Conference   44  Continuing to write the next chapter of cancer and infectious diseases treatment  Looking ahead  Continue responsible management of resources  Sustain and grow  Deliver IND for 3 new ImmTAC candidates  Global site expansion for PRAME-A02 trial (data by 1H 2024)  HIV Phase 1 SAD data expected 2023  
 

 THANK YOU