Brenetafusp

Immunocore presents Phase 1 data of brenetafusp, an ImmTAC bispecific targeting PRAME, in patients with ovarian cancer Brenetafusp is clinically active as monotherapy and in combination with chemotherapy in heavily pre-treated, platinum-resistant ovarian cancer patients T cell fitness gene expression signature in blood is an important parameter of clinical activity for tebentafusp in uveal melanoma and for brenetafusp across different tumor types 14 September 2024 -- Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, today presented Phase 1 data with brenetafusp in patients with platinum resistant ovarian cancer at the 2024 European Society for Medical Oncology (ESMO) Congress. In a proffered session to be held on Monday, September 16, 2024, the Company will present translational Phase 1/2 data with KIMMTRAK® (tebentafusp-tebn) and brenetafusp demonstrating that T cell fitness gene expression signature in blood is an important parameter associated with clinical activity for both therapies in metastatic uveal melanoma. “Brenetafusp monotherapy is active in heavily pre-treated, platinum resistant ovarian cancer patients and can be combined safely with chemotherapy. We see the hallmarks of ImmTAC clinical activity in this Phase 1 data, such as disease control, ctDNA molecular response, and association with T cell fitness, which increases our confidence in the potential for brenetafusp in ovarian cancer,” said David Berman, Head of Research and Development. “While early, the promising efficacy data from chemotherapy plus brenetafusp led us to expand the combinations we are studying, including in earlier-line platinum sensitive disease.” Dr. Claire Friedman, Gynecologic Medical Oncologist & Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center, said: “While many solid tumors have benefited from the advances in immunotherapy, the treatment of recurrent ovarian cancer has remained an ongoing challenge. These data offer proof of concept that patients with advanced, platinum-resistant ovarian cancer can benefit from brenetafusp, alone or in combination with chemotherapy, and support further development of the drug in this patient population.” Thirty-seven patients with heavily pre-treated (median 5 prior lines) serous ovarian cancer were treated with brenetafusp monotherapy, including four patients previously presented in the efficacy data set at ESMO 2022. A majority of patients had received prior bevacizumab (81%) and PARP inhibitors (59%). Brenetafusp was well tolerated with no treatment-related discontinuation or death observed. The most frequent treatment-related adverse event was reversible and manageable cytokine release syndrome, observed in 57% of patients, with the majority being Grade 1. Thirty-one of the 37 monotherapy patients were evaluable for RECIST v1.1 tumor assessment, 58% of whom demonstrated disease control (partial response and stable disease), including two confirmed partial responses (6.5% RECIST response rate). Of patients who had tumor progression, 64% were treated beyond progression (median of 2 additional months). Across all 37 patients, the median progression-free survival (PFS) was 3.3 months, and the overall survival (OS), while still maturing, was 73% at 6 months. Of the 29 monotherapy patients evaluable for circulating tumor DNA (ctDNA) response, 31% (9/29) had a molecular response (≥0.5 log reduction by week 9). Twenty-eight monotherapy patients were evaluable for baseline blood T cell fitness (TCF) gene expression signature. There was greater activity in patients with a TCF signature above median versus those at or below the median, respectively, including: disease control (80% vs 38%), PFS (3.7 months vs 2.2 months) and six-month OS (93% vs 47%). As presented today at ESMO in a pre-clinical study poster (1021P), the combination of chemotherapy with brenetafusp has the potential to enhance clinical activity by increasing expression of the antigen presentation machinery in cancer cells. In the Phase 1 trial, 16 patients with platinum-resistant ovarian cancer were treated with brenetafusp and either gemcitabine, nab-paclitaxel or pegylated doxorubicin chemotherapy. These patients were heavily pre-treated (median of 4 prior treatment lines) including prior bevacizumab (75%) and PARP inhibitors (75%). The safety profile of brenetafusp in combination with chemotherapy was consistent with the expected profile of each individual agent. Thirteen of the 16 combination patients were evaluable for RECIST v1.1 tumor assessment. All 13 patients received prior platinum and taxane therapy, and 6 received prior gemcitabine. Sixty nine percent (9/13) of patients achieved disease control, including three partial responses (23% RECIST response rate). Historical chemotherapy efficacy data in this heavily pre-treated patient population is sparse but indicate response rates are less than 10%, with disease control rates typically ~40-50%1. Eleven of the 16 combination patients were evaluable for ctDNA response. The molecular response rate was 82% (9/11). As previously reported for brenetafusp in cutaneous melanoma (ASCO 2024), ctDNA molecular response in this trial was also associated with longer OS and PFS. At an oral proffered session on Monday, September 16, 2024, the Company will present translational data from previously treated, metastatic uveal melanoma (mUM) patients, including 132 patients treated with KIMMTRAK in a Phase 1/2 trial, and 22 patients treated with brenetafusp in a Phase 1 trial. In the KIMMTRAK cohort, patients with a TCF signature greater than or equal to the median had higher clinical activity compared to patients with a TCF signature below the median, respectively, including longer OS (28 months vs 11 months), PFS (5 months vs 2 months) and disease control (67% vs 36%). The association of TCF signature with longer OS was independent of known prognostic factors in uveal melanoma. In addition, the TCF signature was associated with greater tumor reduction and a higher rate of on-target, melanocyte-related adverse events; both are consistent with the mechanism of action, and suggest that the signature is not purely prognostic. This TCF signature, discovered for KIMMTRAK in mUM, was subsequently confirmed as an important parameter of clinical activity for brenetafusp in mUM (ESMO 2024), ovarian cancer (ESMO 2024), and cutaneous melanoma (ASCO 2024). The accumulating data suggests that ImmTAC therapies may deliver greater clinical activity in earlier line patients, where TCF is expected to be higher, leading the Company to investigate brenetafusp in these populations. Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune “cold” low mutation rate tumors. IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company is enrolling patients into three expansion arms in ovarian, NSCLC, and endometrial cancers. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care, including checkpoint inhibitors, chemotherapy, and tebentafusp. Most patients with ovarian cancer are diagnosed with advanced disease, giving it the highest mortality amongst gynecological malignancies in the US and Europe. The current standard of care is surgery followed by platinum-based chemotherapy, and although many patients initially respond, the disease often recurs and, over time, becomes resistant to further platinum therapy. There is significant unmet need for new therapies that improve clinical outcomes in both platinum-sensitive and platinum-resistant ovarian cancer patients. Uveal melanoma is a rare and aggressive form of melanoma affecting the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK. KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273. Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases, and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including nine active clinical and pre-clinical programs​ in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. The content above comes from the network. if any infringement, please contact us to modify.

KIMMTRAK® (tebentafusp-tebn) net revenues of $75.3 million in 2Q 2024 driven by US growth Registrational Phase 3 TEBE-AM trial with KIMMTRAK in previously treated cutaneous melanoma ongoing, following conversion of Phase 2/3 trial – expect to complete enrollment in 1H 2026 Registrational Phase 3 (PRISM-MEL-301) evaluating brenetafusp + nivolumab in first-line cutaneous melanoma started randomization Presented Phase 1 data of brenetafusp in late-line cutaneous melanoma patients at ASCO 2024; late-line high-grade serous ovarian data to be presented at ESMO 2024 Conference call today, August 8, 2024 at 8:00 AM ET, 1:00 PM BST (OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & ROCKVILLE, Md., US, 08 August 2024) Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, today announced its financial results for the second quarter ended June 30, 2024 and provided a business update. “Over the next 18 months, we will present multiple data read-outs including brenetafusp and the HIV MAD data, while progressing three Phase 3 trials, with registrational data expected in 2026, 2027 and 2028. We will also advance our new autoimmune and oncology clinical and pre-clinical programs,” said Bahija Jallal, Chief Executive Officer of Immunocore. “In the first half of 2024, we expanded KIMMTRAK’s reach in the US community setting and globally with 9 new launches and 2 additional reimbursement agreements, in the context of a challenging market access environment in Europe,” said Ralph Torbay, Immunocore’s Chief Commercial Officer. “We are exploring the potential of KIMMTRAK to benefit more patients and deliver revenue growth beyond metastatic uveal melanoma with our two ongoing Phase 3 registrational trials in previously treated cutaneous melanoma and in adjuvant uveal melanoma.” Second Quarter 2024 Highlights (including post-period) KIMMTRAKThe Company’s lead product, KIMMTRAK, is approved in 38 countries and has been launched in 19 countries globally to date for HLA-A*02:01 positive patients with unresectable or metastatic uveal melanoma (mUM). KIMMTRAK continues to be the standard of care in most markets where it is launched. The Company sees three key growth areas for the KIMMTRAK opportunity, including: continued global expansion in mUM, as well as the potential expansion into 2L+ advanced cutaneous melanoma (CM) and adjuvant uveal melanoma. Metastatic uveal melanoma In Q2 2024, KIMMTRAK net product sales were $75 million and $146 million for the three and six months ended June 30, respectively, representing increases of 32% and 34% respectively, compared to the prior year periods.US growth driven by increased penetration in community setting and duration of treatment.As of July 1, 2024, KIMMTRAK is launched in 19 countries. Reimbursement agreements reached in Sweden and Poland with expected launches in second half of 2024.Published data at ASCO 2024 demonstrating that KIMMTRAK-treated mUM patients with stable disease and any confirmed tumor reduction have similar clinical outcomes to patients with RECIST partial response.New T cell fitness insights from the Phase 2 KIMMTRAK trial in previously treated uveal melanoma will be an oral presentation during the “Basic Science & Translational Research” proffered session at the 2024 ESMO Congress. 2L + Previously treated cutaneous melanoma Converted Phase 2/3 TEBE-AM trial into registrational Phase 3 trial, which will continue three arms: KIMMTRAK monotherapy, KIMMTRAK in combination with pembrolizumab, and control.Over 120 patients already randomized into the original Phase 2 portion will now be included in the Phase 3 trial, which we expect will accelerate time to final endpoint by up to 12 months.Expect enrollment to be completed in the first half of 2026. Adjuvant uveal (or ocular) melanoma Randomization in the ATOM Phase 3 trial, led by the European Organisation for Research and Treatment of Cancer (EORTC), expected to start in the second half of 2024. PRAME franchiseBrenetafusp (IMC-F106C) is the Company’s lead PRAME-A02 ImmTAC bispecific candidate. Brenetafusp is being evaluated in combination with nivolumab, in a Phase 3 registrational trial (PRISM-MEL-301) in patients with first-line advanced cutaneous melanoma (CM) and in a Phase 1/2 clinical trial, as monotherapy and in combination, across multiple tumor types, including platinum resistant ovarian, non-small cell lung (NSCLC), and endometrial carcinoma. PRISM-MEL-301 – First PRAME Phase 3 clinical trial with brenetafusp in first-line advanced or metastatic HLA-A*02:01 positive cutaneous melanoma In 2Q, the Company randomized the first patient in PRISM-MEL-301.Trial is evaluating brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab. Phase 1/2 clinical trial of brenetafusp (PRAME-A02) in multiple solid tumors Presented data at ASCO 2024 from the Phase 1/2 trial with brenetafusp in patients with late-line CM showing promising brenetafusp monotherapy disease control (partial response and stable disease), progression free survival (PFS), and circulating tumor DNA (ctDNA) molecular response. In PRAME positive patients, the disease control rate was 58% and median PFS was 4.2 months. Brenetafusp was well tolerated as monotherapy and in combination with anti-PD1.Clinical data from monotherapy and chemotherapy combinations in heavily pre-treated platinum-resistant high grade serous ovarian cancer will be presented as a poster at ESMO 2024 (Phase 1 safety and efficacy of brenetafusp, a PRAME × CD3 ImmTAC T cell engager, in platinum resistant ovarian cancer (PROC), Poster 750P). The next step is to further evaluate brenetafusp in combination with non-platinum chemotherapies in platinum resistant disease and to test the combination with platinum chemotherapy and with bevacizumab in platinum sensitive disease.The Company plans to present clinical data for brenetafusp in late-line non-small cell lung cancer (NSCLC) in the fourth quarter of 2024. The next step is to evaluate brenetafusp in combinations with docetaxel and with osimertinib in earlier-line NSCLC. IMC-P115C (PRAME-A02 Half-Life Extended) & IMC-T119C (PRAME-A24) Submitted Clinical Trial Application (CTA) for IMC-P115C in the second quarter of 2024, which is currently under review.Remain on track for regulatory submission of Investigational New Drug (IND) or Clinical Trial Application (CTA) for IMC-T119C in the fourth quarter of 2024. Additional Oncology Candidates IMC-R117C (first PIWIL1-A02 targeted immunotherapy) for colorectal and other gastrointestinal cancersThe Company has leveraged its proprietary peptidomic database to validate a novel target, PIWIL1. PIWIL1 is a negative prognostic marker and is expressed across a range of tumors including colorectal, which is historically insensitive to immune checkpoints, as well as gastro-esophageal, and pancreatic cancer. The CTA for IMC-R117C was accepted in April 2024 by the EMA, and the Phase 1 clinical trial is expected to start in the second half of 2024. ImmTAV Candidates for a Functional Cure in Infectious DiseasesThe Company’s bispecific TCR technology platform has potential to offer a new approach for the treatment of chronic infections and aims to eliminate evidence of remaining virus in circulation after the patient stops taking medication - known as a "functional cure". Two investigational candidates are in Phase 1 clinical trials for people living with human immunodeficiency virus (HIV) and people with chronic Hepatitis B infection (HBV). Phase 1 trial of IMC-M113V (Gag-A02) for people living with HIV The objective of the clinical trial is to identify a safe and tolerable dose and evaluate whether IMC-M113V could lead to reduction in the viral reservoir and, after stopping antiretroviral therapies (ART) and IMC-M113V, delay or prevent HIV rebound.Historically, viral rebound occurs rapidly after ART interruption at a median of 2 weeks, and approximately 98% of people will have >200 viral copies/ml (the threshold for transmission) by week 8 (Feher C et. al, 2019).In the MAD portion, the Company has enrolled 3 cohorts with 5 people living with HIV (PLWH) per cohort. The highest tested dose is 300 mcg.A biologically active dose has been reached and the Company plans to enroll more PLWH to characterize anti-viral activity and to explore higher doses. This will move the planned data release from fourth quarter of 2024 into first quarter of 2025. Phase 1 trial of IMC-I109V (Envelope-A02) for people living with HBV or HBV-positive hepatocellular carcinoma Patient enrollment continues into the single ascending dose portion of the clinical trial. Tissue-specific Down Modulation of the Immune System for Autoimmune DiseasesThe Company is expanding its platform into autoimmune diseases with two new, first-in-class bispecific candidates recently entering its pipeline. The key differentiator of the Company’s ImmTAAI (Immune Modulating Monoclonal TCRs Against AutoImmune disease) platform is tissue-specific down modulation of the immune system whereby, when tethered to the tissue of interest, the new candidates suppress pathogenic T cells via PD1 receptor agonism. IMC-S118AI (pre-pro insulin A02 x PD1), intended for disease-modifying treatment in type 1 diabetes IMC-S118AI recognizes a peptide from pre-proinsulin presented by HLA-A02 on beta cells, coupled with a PD1 agonist effector arm.IMC-S118AI is advancing towards GMP manufacturing in 2024. Undisclosed non-HLA restricted (universal) candidate for inflammatory dermatological diseases The candidate is an antigen presenting cell (APC) tethered ImmTAAI and is not HLA restricted (i.e. universal for all populations). ESMO Congress 2024 - Presentation and poster details Title: Phase 1 safety and efficacy of brenetafusp, a PRAME × CD3 ImmTAC T cell engager, in platinum resistant ovarian cancer (PROC) (Poster 750P)Presenting author: Claire F. FriedmanSession: Poster Session – Gynaecological cancers, Saturday 14 September 2024; 09:00 a.m. - 5:00 p.m. CEST / 04:00 a.m. - 12:00 p.m. ET Title: Chemotherapy and hypomethylating agents enhance anti-tumor activity of PRAME ImmTAC Presenting author: Adel BenlahrechSession: Poster Session – Investigational immunotherapy, Saturday 14 September 2024; 09:00 a.m. - 5:00 p.m. CEST / 04:00 a.m. - 12:00 p.m. ET (Poster 1021P) Title: Association of a blood T cell fitness gene signature with clinical benefit from ImmTAC bispecific T cell engagers (Oral 66O) Presenting author: Joseph SaccoSession: Proffered paper session 2 – Basic Science and Translational Research, Monday 16 September 2024; 02:45-04:15 p.m. CEST / 09:45-11:15 a.m. ET Financial ResultsFor the second quarter ended June 30, 2024, the Company generated net product sales of $75.3 million compared to $56.9 million for the same period in 2023. This increase was due to revenue from KIMMTRAK, of which $55.6 million was in the United States, $15.4 million (net of an increase in estimated reserves related to prior periods of $6.7 million) in Europe, and $4.3 million in international regions. The increase in net product sales was due primarily to increased volume in the United States and global country expansion, as the Company continued its commercialization efforts. For the second quarter ended June 30, 2024, research and development (R&D) expenses were $51.1 million, compared to $38.2 million for the same period in 2023. This increase was primarily driven by expenses incurred for the PRAME programs, including the initiation of the Company’s Phase 3 clinical trial. For the quarter ended June 30, 2024, SG&A expenses were $38.6 million, compared to $35.0 million for the same period in 2023. This increase was primarily related to additional employees engaged in business support functions, including medical and regulatory activities, to support our growing pipeline and commercial activities. Basic and diluted loss per share was $0.23 for the quarter ended June 30, 2024, as compared to a basic and diluted loss per share of $0.35 for the same period in 2023. Net loss for the quarter ended June 30, 2024 was $11.6 million, as compared to $17.0 million for the same period in 2023. Cash, cash equivalents, and marketable securities at June 30, 2024 were $859.6 million. The Company plans to use $50 million to repay its existing loan by the end of 2024, and also expects to pay approximately $40 million in sales-related rebate accruals in the second half of 2024. About ImmTAC® molecules for cancer Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune “cold” low mutation rate tumors. About ImmTAV® molecules and infectious diseases ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules are novel bispecifics that are designed to enable the immune system to recognize and eliminate virally infected cells. Immunocore is advancing clinical candidates to achieve functional cure for patients with HIV and hepatitis B virus (HBV). The Company aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. For the treatment of HBV, the Company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic HBV. About ImmTAAITM molecules and autoimmune diseases ImmTAAI (Immune mobilizing monoclonal TCRs Against AutoImmune disease) molecules are novel bispecifics that are designed for tissue-specific down modulation of the immune system. When tethered to the tissue of interest, ImmTAAI candidates suppress pathogenic T cells via PD1 receptor agonism. The Company is currently advancing two candidates for autoimmune diseases, including type 1 diabetes and inflammatory dermatological diseases. About PRISM-MEL-301 (NCT06112314) – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma The Phase 3 registrational trial is randomizing HLA-A*02:01-positive patients with previously untreated advanced melanoma to brenetafusp + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two brenetafusp dose regimens (40 mcg and 160 mcg) and a control arm. One of the two brenetafusp dose regimens will be discontinued after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR). About the IMC-F106C-101 Phase 1/2 trial IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumors, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company is enrolling patients into three expansion arms in NSCLC, as well as ovarian and endometrial carcinomas. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care, including checkpoint inhibitors, chemotherapy, and tebentafusp. About TEBE-AM – Phase 3 registrational trial with tebentafusp in previously treated advanced cutaneous melanoma The trial is randomizing patients with second-line or later advanced cutaneous melanoma who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients are randomized to one of three arms, including tebentafusp – as monotherapy or in combination with an anti-PD1 – or a control arm. The primary endpoint is overall survival. About the ATOM Phase 3 trial The EORTC-led Phase 3 clinical trial will include sites in 10 EU countries and the United States and will randomize HLA-A*02:01-positive patients with high-risk primary uveal melanoma after definitive treatment, by surgery or radiotherapy, and no evidence of metastatic disease on imaging. The trial is expected to enroll a total of 290 patients who will be randomized 1:1 to one of two arms: tebentafusp as monotherapy or observation. The primary endpoint of the trial is relapse-free survival (RFS), with secondary objectives of overall survival and safety and tolerability of tebentafusp. Exploratory objectives include comparison of health-related quality of life between the treatment arms and evaluation of the role of circulating tumor DNA (ctDNA) as a biomarker for the presence of residual disease. About Uveal Melanoma Uveal melanoma is a rare and aggressive form of melanoma affecting the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK. About Cutaneous Melanoma Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments. About KIMMTRAK® KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform, designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. IMPORTANT SAFETY INFORMATION Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK, with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS. Skin Reactions Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions. Elevated Liver Enzymes Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity. Embryo-Fetal Toxicity KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose. The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate. For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS). About KIMMTRAKConnect Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273. About Immunocore Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including nine active clinical and pre-clinical programs​ in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may”, “will”, “believe”, “expect”, “plan”, “anticipate” 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 press release are forward-looking statements. These statements include, but are not limited to, statements regarding the commercial performance of KIMMTRAK; the potential benefits and advantages that KIMMTRAK will provide for patients, including its potential for expansion into other indications such as cutaneous and adjuvant uveal melanoma; expectations regarding the design, progress, timing, enrollment, randomization, scope, expansion, funding, and results of the Company’s existing and planned clinical trials; the timing and sufficiency of clinical trial outcomes to support potential approval of any of the Company’s product candidates or those of, or combined with, its collaboration partners; the Company’s goals to develop and commercialize product candidates based on its KIMMTRAK platform alone or with collaboration partners; the expected submission of investigational new drug applications or clinical trial applications; the potential regulatory approval, expected clinical benefits and availability of the Company’s product candidates; and the use of the Company’s cash, cash equivalents and maketable securities. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, the impact of worsening macroeconomic conditions on the Company’s business, financial position, strategy and anticipated milestones, including Immunocore’s ability to conduct ongoing and planned clinical trials; Immunocore’s ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products; Immunocore’s ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK; Immunocore’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; 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 patient enrollment delays or otherwise; 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; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore’s need for and ability to obtain additional funding, on favorable terms or at all, including as a result of worsening macroeconomic conditions, including changes in inflation and interest rates and unfavorable general market conditions, and the impacts thereon of the war in Ukraine, the conflict between Hamas and Israel, and global geopolitical tension; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; 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 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on February 28, 2024, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the SEC. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law. Contact Information Immunocore Sébastien Desprez, Head of CommunicationsT: +44 (0) 7458030732E: sebastien.desprez@immunocore.comFollow on Twitter: @Immunocore Investor RelationsClayton Robertson, Head of Investor RelationsT: +1 (215) 384-4781E: ir@immunocore.com Immunocore Holdings plc Condensed Consolidated Statement of Operations Comparison of the Quarters and Year to Date Ended June 30, 2024 and 2023 (In thousands, except share and per share data)(Unaudited) Quarter Ended Year to Date June 30, 2024June 30, 2023 June 30, 2024June 30, 2023Product revenue, net$75,347$56,932 $145,689$108,513Collaboration revenue532,825 2135,903Total revenue75,400 59,757 145,902 114,416 Cost of product revenue(1,707)(346) (1,953)(562)Research and development expense(51,072)(38,158) (108,531)(74,730)Selling, general, & administrative expense(38,638)(35,010) (77,925)(67,577)Loss from operations(16,017)(13,757) (42,507)(28,453)Interest income6,2394,278 14,4857,406Interest expense(4,277)(1,274) (7,516)(2,524)Foreign currency loss(508)(5,880) (2,914)(11,893)Other income (expense), net4,433(190) 4,243(515)Net loss before income taxes(10,130)(16,823) (34,209)(35,979)Income tax expense(1,486)(191) (1,843)(484)Net loss $(11,616)$(17,014) $(36,052)$(36,463) Basic and diluted net loss per share$(0.23)$(0.35) $(0.72)$(0.75) Basic and diluted weighted average number of shares50,014,086 48,694,047 49,944,767 48,440,318 Immunocore Holdings plc Condensed Consolidated Balance Sheets As of June 30, 2024 (In thousands)(Unaudited) Jun '24Dec '23ASSETS Current assets Cash and cash equivalents$504,985$442,626Marketable securities354,612-Accounts receivable, net60,24552,093Prepaid expenses and other current assets33,55529,600Inventory, net3,4624,501Total current assets956,859 528,820 Property and equipment, net7,6849,215Operating lease right of use assets, net32,43533,520Deferred tax assets, net10,11110,973Other non-current assets16,27614,473Total assets$1,023,365 $597,001 Liabilities and shareholders’ equity Current liabilities Accounts payable$19,947$17,798Accrued expenses and other current liabilities163,762119,835Operating lease liabilities, current1,3871,388Total current liabilities185,096 139,021 Accrued expenses, non-current2,089978Deferred revenue, non-current5,4775,515Operating lease liabilities, non-current33,44534,633Interest-bearing loans and borrowings438,12148,011Total liabilities664,228228,158 Shareholders' equity Ordinary shares135134Deferred shares11Additional paid-in capital1,174,1471,149,643Accumulated deficit(780,726)(744,674)Accumulated other comprehensive loss(34,420)(36,261)Total shareholders' equity359,137 368,843 Total liabilities and shareholders' equity$1,023,365 $597,001 Immunocore Holdings plc Summary Condensed Consolidated Statements of Cash Flows For the Year to Date Period Ended June 30, (In thousands)(Unaudited) June '24June '23 Cash and cash equivalents at beginning of period$442,626$402,472Net cash provided by operating activities18,88510,584Net cash used in investing activities(350,761)(4,396)Net cash provided by financing activities395,19417,716Net foreign exchange difference on cash held(959)5,619Cash and cash equivalents at end of period$504,985$431,995