On January 10, 2025 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, reported its strategic priorities for 2025 including its plans for reaching more patients with melanoma and other diseases with high unmet needs (Press release, Immunocore, JAN 10, 2025, View Source [SID1234649591]).
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The Company also highlights the potential of its melanoma franchise building on KIMMTRAK’s performance and reveals details of IMC-U120AI (CD1a x PD1), its first non-HLA restricted candidate. This second autoimmune therapy adds to the Company’s pipeline of ImmTAX candidates across three therapeutic areas. The updates will be shared during a presentation at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco.
"Since launching the world’s first bispecific TCR therapy, we have made KIMMTRAK available to patients in 23 countries. We are now building a melanoma franchise through life cycle management with two Phase 3 KIMMTRAK trials, and with the brenetafusp Phase 3 trial in first-line melanoma. We anticipate topline results for the first of these three pivotal trials in 2026," said Bahija Jallal, Immunocore’s Chief Executive Officer. "In 2025, we plan to report initial multiple ascending dose data for our HIV TCR therapy, expand enrollment in multiple oncology Phase 1/2 trials, including our PRAME and PIWIL1 programs, and advance our autoimmune candidates toward the clinic."
Key Strategic Priorities 2025
Immunocore’s mission is to bring transformative medicines to patients with cancer, infectious diseases, and autoimmune diseases. In 2025, the Company’s priorities will be:
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Building a melanoma franchise – reaching more metastatic uveal melanoma (mUM) patients and delivering KIMMTRAK’s lifecycle management program through two ongoing registrational Phase 3 trials (TEBE-AM and ATOM). The Company is also enrolling a third registrational trial, PRISM-MEL-301, evaluating brenetafusp in first-line melanoma.
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Advancing the clinical portfolio – enrolling patients in multiple Phase 1 oncology trials with brenetafusp (PRAME-A02), IMC-P115C (PRAME-A02-HLE), IMC-R117C (PIWIL1-A02), and IMC-M113V in HIV.
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Innovating for sustainable growth – planning to submit a clinical trial application (CTA) for the Company’s two autoimmune disease candidates: IMC-S118AI (PPI x PD1) by year end 2025 and IMC-U120AI (CD1a x PD1) in 2026.
Building a melanoma franchise
In 2025, Immunocore will continue expanding access to KIMMTRAK to more patients with mUM globally, through additional launches and approvals, building on the 38 country approvals and 23 launches as of year-end 2024.
In countries where KIMMTRAK has been launched, the Company will continue to focus on reaching more patients in the community and highlighting the three-year overall survival data.
The Company is enrolling patients in three registrational Phase 3 trials, with the first topline results anticipated in 2026 and a potential to reach up to 15,000 additional patients across three new melanoma indications:
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TEBE-AM – trial evaluating KIMMTRAK for HLA-A*02:01 in second-line and later cutaneous melanoma – with a potential to address up to 4,000 previously treated advanced cutaneous melanoma patients. This is an area of great unmet need where no therapy has shown an Overall Survival (OS) improvement in a randomized clinical trial.
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PRISM-MEL-301 – trial evaluating brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab for HLA-A*02:01 patients with first-line, advanced or metastatic cutaneous melanoma. Despite approved therapies, there remains an unmet need, and there is the potential to address an estimated 10,000 patients.
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ATOM – led by the European Organisation for Research and Treatment of Cancer (EORTC) to evaluate KIMMTRAK as adjuvant therapy for uveal (or ocular) melanoma for HLA-A*02:01 patients. The Company estimates that the HLA-A*02:01 high risk adjuvant uveal melanoma patient population could be up to 1,200 patients.
Advancing the clinical portfolio
In 2025, beyond executing the three ongoing registrational trials in three additional melanoma indications, Immunocore will continue to enroll patients in the multiple ongoing Phase 1 trials in oncology and infectious diseases, to evaluate safety and efficacy across several cohorts. The Company will also use its translational medicine (i.e. ctDNA, T cell fitness) dataset from more than a thousand patients treated in the clinic with KIMMTRAK and its investigational therapies to inform clinical development.
PRAME portfolio
The Company is evaluating brenetafusp in a Phase 1/2 trial in combination with non-platinum chemotherapies in platinum resistant ovarian cancer (PROC) and with bevacizumab or with platinum chemotherapy in earlier lines of platinum sensitive ovarian cancer (PSOC). In the same trial, the Company continues signal detection in metastatic non-small cell lung cancer (NSCLC) cohorts, including brenetafusp in combination with docetaxel and with osimertinib in earlier-line NSCLC.
The Company has recently started enrolling patients in the Phase 1 dose escalation trial with IMC-P115C (PRAME-A02-HLE) in multiple solid tumors. IMC-P115C is the Company’s half-life extended ImmTAC therapy – targeting the same PRAME peptide and with the same CD3 effector and TCR specificity as brenetafusp – and is designed to improve patient convenience by reducing the frequency of treatment administration.
PIWIL1-A02
The third ongoing Phase 1 clinical trial in oncology is evaluating the safety and clinical activity of IMC-R117C (targeting PIWIL1) in HLA-A*02:01-positive patients with advanced solid tumors, including colorectal cancer, as a single agent and in combination with standards of care.
Infectious diseases
The Company continues to enroll people living with HIV (PLWH) in the multiple ascending dose (MAD) part of the Phase 1 clinical trial with IMC-M113V and will present initial data during the first quarter of 2025. The trial aims to identify a safe and tolerable dosing schedule, test whether IMC-M113V could lead to reduction in the viral reservoir and, after stopping all therapies (antiretroviral therapies and IMC-M113V), delay or prevent HIV rebound (known as functional cure). A biologically active dose has been reached, and the Company is enrolling more PLWH to characterize anti-viral activity and to explore higher doses.
The Company plans to present data from the single ascending dose (SAD) portion of the Phase 1 trial with IMC-I109V for people living with hepatitis B virus (HBV) in 2025.
Innovating for sustainable growth
Immunocore will continue pioneering immunotherapy and unlocking the full potential of its platform to generate transformative treatments for patients, by using different targeting mechanisms and immune effectors for next-generation bispecific therapies.
This approach is most recently illustrated by the Company’s second candidate in autoimmune diseases, IMC-U120AI, which is also its first non-HLA restricted (i.e. universal for all populations) program.
Autoimmune diseases
The key differentiator of the ImmTAAI platform is tissue-specific down modulation of the immune system as the candidates suppress pathogenic T cells via PD1 receptor agonism only when tethered to the target tissue.
In the second half of 2025, the Company plans to file a CTA for its first candidate – IMC-S118AI (PPI x PD1) – targeted specifically to the pancreatic beta-cell and intended as a disease-modifying treatment in type 1 diabetes. IMC-S118AI recognizes a peptide from pre-pro-insulin presented by HLA-A02 on beta cells, coupled with a PD1 agonist effector arm.
The Company announced today its second autoimmune candidate. IMC-U120AI (CD1a x PD1) is a CD1a-tethered PD1 agonist ImmTAAI therapy. CD1a is an HLA-like protein that is expressed on skin and mucosal antigen presenting cells, such as Langerhans cells. It plays an important role in triggering allergic inflammation in atopic dermatitis and potentially other immune diseases. The Company plans to file a CTA in 2026 for a Phase 1 trial in atopic dermatitis for this candidate.
Corporate updates
In January 2025, Travis Coy was appointed Executive Vice President, Chief Financial Officer and Head of Corporate Development. Travis brings with him over 20 years of experience working at Eli Lilly and Company, where his most recent role was Vice President, Head of Transactions and M&A, Corporate Business Development.
Preliminary Year-End 2024 cash position
Preliminary unaudited cash, cash equivalents and marketable securities were approximately $820 million as of December 31, 2024. In the fourth quarter of 2024, the Company prepaid in full the loan outstanding under the Pharmakon Loan Agreement and also paid sales-related rebate accruals. These preliminary unaudited results are subject to adjustment. Immunocore will report its final and complete fourth-quarter and full-year 2024 financial results in late February 2025, and the actual results could be different from these preliminary unaudited financial results.
43rd Annual J.P. Morgan Healthcare Conference
The Company has updated its corporate presentation to reflect its business and strategic updates. The Immunocore management team will discuss these updates during a live and webcast presentation at the 43rd Annual J.P. Morgan Healthcare Conference, on Wednesday, January 15, 2025, at 8:15 a.m. Pacific Standard Time (PST). The presentation and webcast will be available in the ‘Investors/Media’ section of Immunocore’s website at www.immunocore.com. A replay of the presentation will be made available for a limited time.
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 for 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 for 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 and ovarian 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 currently focusing on enrolling patients in combination arms with standards-of-care across multiple tumor types.
About the 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 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. There is a significant unmet need in the adjuvant setting due to the high risk of metastasis and no effective treatment options. Approximately 50% of patients develop metastatic disease, often leading to poor survival outcomes.
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.