On November 7, 2023 Immunocore Holdings plc (Nasdaq: IMCR), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious diseases and autoimmune conditions, reported its financial results for the third quarter ended September 30, 2023, and provided a business update (Press release, Immunocore, NOV 7, 2023, View Source [SID1234637143]).
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"We are proud to have simultaneously published in the New England Journal of Medicine and presented at ESMO (Free ESMO Whitepaper) 2023 the unprecedented three-year survival follow-up from our pivotal trial of KIMMTRAK in metastatic uveal melanoma," said Bahija Jallal, Immunocore’s Chief Executive Officer. "We continue to pioneer TCRs by exploring KIMMTRAK in the adjuvant setting with the EORTC-sponsored ATOM Phase 3 clinical trial and progressing the PRAME franchise in multiple solid tumors."
Third Quarter 2023 Highlights (including post-period)
KIMMTRAK
KIMMTRAK (tebentafusp-tebn) for metastatic uveal melanoma (mUM)
KIMMTRAK is approved in over 35 countries globally. Total net product revenue arising from the sale of KIMMTRAK (or "net sales") was £49.7 million (or $60.7 million) in the third quarter of 2023, an increase of 9% (or 5% in USD*) compared to the second quarter of 2023, of which £34.5 million (or $42.1 million) was in the United States, £15.0 million (or $18.3 million) in Europe, and £0.2 million (or $0.3 million) in Rest of World.
Commercial sales have increased in the United States and European countries, including France, Germany and Italy, during the third quarter. In early August, the Company signed a KIMMTRAK pricing reimbursement agreement with authorities in Germany. Since the beginning of 2023, we have launched KIMMTRAK in Austria, Israel, Italy, Finland, Switzerland and Belgium, and have recently reached price agreements with Canada and Australia.
In October, the Company published in the New England Journal of Medicine and presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 Congress long-term overall survival (OS) data from the KIMMTRAK (tebentafusp-tebn) Phase 3 clinical trial in previously untreated HLA-A*02:01 positive patients with metastatic uveal melanoma. The longest of any randomized trial for metastatic uveal melanoma, the trial demonstrated a three-year OS rate of 27% in the tebentafusp arm, versus 18% in the control arm (investigator’s choice, predominantly [82%] single agent pembrolizumab).
In October, the Company signed an agreement for a European Organisation for Research and Treatment of Cancer (EORTC)-sponsored trial to study tebentafusp as adjuvant therapy of uveal (or ocular) melanoma (ATOM). The Phase 3 trial will randomize HLA-A*02:01 positive patients after definitive treatment of high-risk primary uveal melanoma and no evidence of metastatic disease on imaging. Patients will be randomized to one of two arms: KIMMTRAK as monotherapy or observation. The primary endpoint of the trial is relapse-free survival (RFS). The Company anticipates that the EORTC will randomize the first patient in the trial in 2024. The EORTC is a non-profit cancer research organization with a mission to coordinate and conduct international translational and clinical research to improve the standard of cancer treatment for patients.
In October, the Company won the prestigious Galenus von Pergamon Prize (the German Prix Galien) for best ‘Orphan Drug’ for KIMMTRAK, adding to the French award for best ‘Medicine in Innovative Therapeutics’ received in 2022.
TEBE-AM – Phase 2/3 trial with KIMMTRAK in second-line or later cutaneous melanoma
Randomization continues in the Phase 2/3 clinical trial of KIMMTRAK in HLA-A*02:01 positive patients with second-line or later cutaneous melanoma. The trial is randomizing patients with advanced melanoma who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF inhibitor. Patients are being randomized to one of three arms, including KIMMTRAK as monotherapy or in combination with an anti-PD1, and a control arm. The trial has a dual primary endpoint of OS and circulating tumor DNA (ctDNA) reduction. The Company expects to complete randomization of the Phase 2 portion of the trial in the second half of 2024.
PRAME franchise
PRISM-MEL301 – First PRAME Phase 3 trial with IMC-F106C in first-line cutaneous melanoma
In August, the Company announced the planned start of a registrational Phase 3 trial with IMC-F106C in cutaneous melanoma. The trial will randomize patients with HLA-A*02:01 positive, first-line cutaneous melanoma to IMC-F106C + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The Company plans to randomize the first patient in this trial in the first quarter of 2024.
Phase 1/2 IMC-F106C targeting PRAME-A02 in multiple solid tumors
In addition to progressing IMC-F106C into a registrational trial in cutaneous melanoma, the Company is continuing to enroll patients in the monotherapy and combination arms of the Phase 1/2 clinical trial across multiple tumor types, including expansion arms for patients with advanced ovarian, non-small cell lung, endometrial, and melanoma cancers. In August, the Company provided an updated analysis of the original 18 melanoma patients (initially presented at ESMO (Free ESMO Whitepaper) in September 2022), which continues to show promising durability of the clinical activity (range of duration of partial response from 6 months to 17 months). The Company expects to report data from the trial in the first half of 2024.
IMC-P115C (PRAME-A02 HLE), IMC-T119C (PRAME-A24)
The Company continues to work on expanding the PRAME franchise, with pre-clinical work ongoing for two new PRAME ImmTAC candidates, IMC-P115C (PRAME-A02 HLE) and IMC-T119C (PRAME-A24) for solid tumors, with both on-track for investigational new drug (IND) or clinical trial application (CTA) submission in 2024.
Early oncology pipeline
IMC-R117C (PIWIL1)
The Company remains on-track to submit an IND/CTA in the fourth quarter of 2023 for IMC-R117C, an ImmTAC targeting the PIWIL1 protein for colorectal and other gastrointestinal cancers. The Company believes this is the first PIWIL1-targeted immunotherapy in development.
Infectious diseases
IMC-M113V and IMC-I109V: aiming for functional cure in HIV and HBV
The Company continues to enroll people living with HIV in the multiple ascending dose (MAD) part of a Phase 1 clinical trial with IMC-M113V, to identify a safe and tolerable dosing schedule. This study will also test whether IMC-M113V could lead to reduction in the viral load and, after stopping all therapies (antiretroviral therapies and ImmTAV), delay or prevent HIV rebound (known as functional cure). The MAD part of the trial will enroll up to 28 participants. The Company expects to present a data update in 2024.
A Phase 1 clinical trial with IMC-I109V, enrolling people living with HBV, is ongoing and continues to enroll patients in the single ascending dose portion of the trial. In August, the Company announced that the multiple dose portion of the trial has been amended to include patients with HBV-positive hepatocellular carcinoma.
Corporate Updates
The Company appointed John Goll as Senior Vice President (SVP), Finance and Chief Accounting Officer. Prior to joining Immunocore, he served as the SVP, Chief Accounting Officer at Insmed. Additionally, the Company appointed John Trainer as SVP, Chief Operating Officer. Prior to joining the Company, John served as the Chief Financial Officer at NexImmune.
Financial Results
Total net product revenue arising from the sale of KIMMTRAK was £49.7 million ($60.7 million) and £137.3 million ($167.7 million) in the three and nine months ended September 30, 2023, respectively, of which £34.5 million ($42.1 million) and £96.9 million ($118.3 million) was in the United States, £15.0 million ($18.3 million) and £39.5 million ($48.3 million) was in Europe, and £0.2 million ($0.3 million) and £0.9 million ($1.1 million) was in Rest of World. For the three and nine months ended September 30, 2022, the Company recorded total net product and pre-product revenue of £36.3 million and £74.5 million, respectively.
For the three and nine months ended September 30, 2023, the Company’s research and development expenses were £31.7 million ($38.7 million) and £88.9 million ($108.6 million), respectively, as compared to £23.3 million and £62.0 million for the three and nine months ended September 30, 2022, respectively. For the three and nine months ended September 30, 2023, the selling and administrative expenses were £20.3 million ($24.8 million) and £87.5 million ($106.8 million), respectively, compared to £11.7 million and £50.6 million for the three and nine months ended September 30, 2022, respectively.
Basic and diluted profit per share for the three months ended September 30, 2023 was £0.04 (or $0.05 and $0.04, respectively), as compared to basic profit per share of £0.13 and diluted profit per share of £0.12 for the three months ended September 30, 2022. Basic and diluted loss per share for the nine months ended September 30, 2023 was £0.59 (or $0.72), compared to a basic and diluted loss per share of £0.36 for the nine months ended September 30, 2022.
Cash and cash equivalents were £364.0 million ($444.5 million) as of September 30, 2023, compared to £332.5 million as of December 31, 2022.
* The Company maintains its books and records in pounds sterling. For the convenience of the reader, the Company has translated pound sterling amounts as of and for the period ended September 30, 2023 into U.S. dollars at a rate of £1.00 to $1.2214. Comparisons to the three months ended June 30, 2023 are based on previously reported U.S. dollar amounts, which applied a convenience rate of £1.00 to $1.2709.
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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 patients with HLA-A*02:01 positive 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: KIMMTRAK 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 the comparison of the health-related quality of life between the treatment arms and the evaluation of the role of circulating tumor DNA as a biomarker for the presence of residual disease.
About TEBE-AM – Phase 2/3 trial with tebentafusp (gp100xCD3) in second-line or later cutaneous melanoma
The trial is randomizing patients with second-line or later cutaneous melanoma who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients will be randomized to one of three arms including tebentafusp, as monotherapy or in combination with an anti-PD1, and a control arm. The Phase 2 portion of the trial will include 40 patients per arm.
About PRISM-MEL301 – Phase 3 trial with IMC-F106C (PRAMExCD3) in 1L advanced cutaneous melanoma
The Phase 3 registrational trial will randomize patients with previously untreated, HLA-A*02:01 positive, advanced melanoma to IMC-F106C + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The study will initially randomize to three arms: two F106C dose regimens (40 mcg and 160 mcg) and control arm and will discontinue one of the F106C dose regimens 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 ImmTAV molecules and infectious diseases
ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules are novel bispecific molecules that, like ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules, are designed to enable the immune system to recognize and eliminate virally infected cells.
Immunocore is advancing clinical candidates to cure patients with HIV and HBV. The Company aims to achieve a reduction in viral reservoirs to enable sustained control of HIV after stopping antiretroviral 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 hepatitis B.
About Uveal Melanoma
Uveal melanoma is a rare and aggressive form of melanoma, which affects 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 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.