On 09 January, 2023 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), 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, autoimmune and infectious diseases, reported the addition of three new ImmTAC product candidates (targeting PRAME-A24, PRAME-A02 half-life extended [HLE], and PIWIL1) to its pipeline and preliminary unaudited KIMMTRAK (tebentafusp-tebn) 2022 year-end net sales (Press release, Immunocore, JAN 9, 2023, View Source [SID1234626066]).
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"We are so proud of what we have delivered for patients with metastatic uveal melanoma, thanks to the talent and hard work of our experienced team. With $140 million of preliminary net sales for KIMMTRAK for 2022, our solid financial position has enabled us to accelerate the development of our existing pipeline and expand our platform," said Bahija Jallal, Chief Executive Office of Immunocore. "2023 is off to a great start with the continued execution of our ambitious development plan for IMC-F106C as well as today’s announcement of the expansion of our PRAME franchise and the nomination of a novel ImmTAC candidate for GI cancers."
Preliminary Year-End 2022 KIMMTRAK and tebentafusp net sales
The preliminary unaudited total net product and net pre-product revenue (or "net sales") arising from the sales of KIMMTRAK and tebentafusp was ~$50 million in Q4 2022, an increase of ~25% compared to the previous quarter, and ~$140 million for full year 2022. Preliminary unaudited cash and cash equivalents were ~$400 million USD year end 2022.1
1 These dollar amounts were converted using the Dec. 31, 2022 convenience rate of £1 to $1.21.
In 2023, the Company will continue to launch in additional countries and establish KIMMTRAK globally as first line treatment for metastatic uveal melanoma, while exploring how to enhance patient convenience. In addition, the Company is enrolling patients into a Phase 2/3 trial to investigate the potential of tebentafusp in advanced cutaneous melanoma.
Expansion of ImmTAC franchise targeting PRAME
IMC-F106C (PRAME-A02)
Initial Phase 1 data with IMC-F106C targeting PRAME, in the context of HLA-A02, presented in September 2022 at the ESMO (Free ESMO Whitepaper) Congress 2022, demonstrated multiple durable confirmed RECIST responses and a reduction in circulating tumor DNA (ctDNA) in multiple solid tumors.
As previously announced, and following the promising initial data, patient enrollment is ongoing in the four monotherapy expansion arms and multiple combination arms of the trial: cutaneous melanoma, ovarian, non-small cell lung cancer (NSCLC), and endometrial cancers. The IMC-F106C-101 trial is adaptive and enables combinations with standards-of-care including checkpoint inhibitors, chemotherapy, and tebentafusp. These combinations will position the Company to explore IMC-F106C in earlier lines of treatment.
In 2023, the Company plans to continue to expand the clinical trial footprint globally; enrolling additional patients in the expansion arms to understand the breadth of clinical activity across multiple tumor types. The Company expects to report initial data from the monotherapy and combination arms by the first half of 2024.
IMC-T119C (PRAME-A24) & IMC-P115C (PRAME-A02 Half-Life Extended)
IMC-F106C is an ImmTAC targeting PRAME for patients with HLA-A02, which is expressed in approximately 40% of Western populations (United States, Canada, EU). In order to expand the potential of TCR therapy targeting PRAME, the Company is developing IMC-T119C, a first-in-class ImmTAC product candidate targeting a PRAME peptide presented by HLA-A24. HLA-24 is an HLA-type that is estimated to be present in 60% of people in Japan and 15-20% in Western populations.
In addition, the Company is developing IMC-P115C, a half-life extended (HLE) ImmTAC product candidate targeting PRAME-A02, with the aim of improving patient convenience. IMC-P115C targets the same PRAME-A02 peptide and uses the same CD3 end and TCR specificity as IMC-F106C.
First-in-class ImmTAC candidate – IMC-R117C (PIWIL1) for colorectal and other gastrointestinal cancers
The Company has leveraged its proprietary peptidomic database to validate a novel target, PIWIL1. PIWIL1 is believed to play a role in tumor progression 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. PIWIL1 is also reported to be a negative prognostic marker. The Company believes IMC-R117C is the first PIWIL1 targeted immunotherapy and plans to submit an IND in Q4 2023.
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Enrolling ImmTAV candidates for a functional cure in HIV & HBV
The Company continues to enroll patients in the HIV and HBV global Phase 1 clinical trials. The Company plans to report data from the Single Ascending Dose portion of the Phase 1 HIV trial in 2023.
41st Annual J.P. Morgan Healthcare Conference
The Company has updated its corporate presentation to reflect these updates. Additionally, the Immunocore management team will discuss these updates during a live and webcast presentation at the 41st Annual J.P. Morgan Healthcare Conference, on Wednesday January 11, 2023, at 9:00AM P.T. 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.
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About ImmTAV molecules and infectious diseases
ImmTAV (Immune mobilising monoclonal TCRs Against Virus) molecules are novel bispecific molecules that, like ImmTAC (Immune mobilising 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 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 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 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 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, a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, 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.
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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 recognise and kill tumour 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.
About Phase 3 IMCgp100-202 Trial
IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated mUM. KIMMTRAK demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).
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.
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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.