On August 10, 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 diseases, reported its financial results for the second quarter ended June 30, 2023, and provided a business update (Press release, Immunocore, AUG 10, 2023, View Source [SID1234634194]).
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"I am extremely pleased that KIMMTRAK is reaching more patients, with approvals now in over 35 countries, leading to another excellent quarter," said Bahija Jallal, Chief Executive Officer of Immunocore. "I am also excited by the progress of our pipeline, as we announce the first Phase 3 trial with our PRAME-targeted ImmTAC, in first-line cutaneous melanoma."
"IMC-F106C, the first PRAME-targeted bispecific therapy, has demonstrated durable clinical activity in melanoma as monotherapy, leading us to initiate the PRISM-MEL301 Phase 3 trial," commented David Berman, EVP Research and Development, Immunocore. "This melanoma trial, informed by a Type B FDA meeting and with global expert input, will randomize patients to IMC-F106C with nivolumab versus global standards of care of nivolumab with or without relatlimab."
Second Quarter 2023 Highlights (including post-period)
KIMMTRAK (tebentafusp-tebn) for metastatic uveal melanoma (mUM)
KIMMTRAK is approved in over 35 countries globally. Total net product revenue (or "net sales") arising from the sale of KIMMTRAK was £45.5 million (or $57.8 million) in the second quarter of 2023, of which £32.8 million (or $41.7 million) was in the United States, £12.2 million (or $15.5 million) in Europe, and £0.5 million (or $0.6 million) in the rest of the world.
In the United States, growth was driven both by patient expansion and duration of therapy. The Company estimates market share increased to approximately 60% of first-line HLA-A*02:01 positive patients with mUM and that duration of therapy in the real-world setting is tracking towards the greater than nine months seen in the Phase 2 and Phase 3 clinical trials.
In the first half of the year, the Company launched KIMMTRAK in Austria and Israel and, most recently, in Italy and Finland. In France and Germany, KIMMTRAK remains the standard of care for first-line HLA-A*02:01 positive patients with mUM, with nearly all patients in Germany being treated in first-line. In early August, the Company reached a KIMMTRAK pricing reimbursement agreement in Germany. This price, expected to be published in September 2023, is slightly improved from the Company’s accounting assumptions. The Company expects to launch KIMMTRAK in several additional European countries by the end of 2023.
In July, the Centers for Medicare & Medicaid Services (CMS) released the 2024 Proposed Rule for the physician fee schedule. The Proposed Rule names KIMMTRAK as a medicine identified as meeting the proposed criteria for unique circumstances, whereby it would have a proposed increased applicable percentage of unused or discarded product volume subject to refund to CMS, of 45%, and not 10% used for medicines without these unique circumstances. The Proposed Rule is expected to be finalized during the fourth quarter of 2023 with an effective date of January 1, 2024.
In the second quarter, the Company presented data demonstrating:
association between early circulating tumor DNA (ctDNA) reduction and longer overall survival (OS) at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 meeting. ctDNA clearance was higher in previously untreated mUM (37%) compared to previously treated mUM (13%). These data suggest that early ctDNA reduction may be a better predictor of longer OS than radiographic response.
final analysis, minimum follow-up of 3 years, from the Phase 2 trial in mUM at AACR (Free AACR Whitepaper) 2023. The Company plans to present updated 3-year overall survival data from the Phase 3 trial in mUM at a medical conference later this year.
In the second quarter, Sanofi informed Immunocore that they will not be progressing their evaluation of SAR444245 in combination with KIMMTRAK. As such, Sanofi elected to terminate the previously announced clinical trial collaboration, in which Sanofi was responsible for clinical development. Immunocore is no longer responsible for supplying KIMMTRAK for this clinical trial and no other costs are expected.
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 Company presented a trial-in-progress poster at the ASCO (Free ASCO Whitepaper) 2023 meeting, describing the design of the trial, which has a dual primary endpoint of OS and ctDNA reduction. The company expects to complete randomization of the Phase 2 portion of the study in the second half of 2024.
PRISM-MEL301 – First PRAME Phase 3 trial with IMC-F106C in first-line cutaneous melanoma
The Company, following U.S. Food and Drug Administration (FDA) Type B interaction, is planning a registrational Phase 3 trial with IMC-F106C, with the goal of starting by the first quarter of 2024. 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 country. Based on feedback from the FDA, including Project Optimus, the study will initially randomize to three arms – two well-tolerated and clinically active F106C dose regimens (40 mcg and 160 mcg) and the 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 Company plans to randomize the first patient in this trial in the first quarter of 2024. The Company estimates there are over 10,000 newly diagnosed HLA-A*02:01 positive, advanced cutaneous melanoma patients in the G7 per year.
Phase 1/2 IMC-F106C targeting PRAME-A02 in multiple solid tumors
In addition to progressing IMC-F106C into a registrational trial in advanced melanoma, the Company is continuing to enroll patients in the Phase 1/2 trial monotherapy and combination arms across multiple tumor types, including expansion arms for patients with advanced ovarian, non-small cell lung, endometrial, and melanoma cancers. Today, the Company is providing 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.
Early oncology pipeline: IMC-R117C (PIWIL1), IMC-P115C (PRAME-A02 HLE), IMC-T119C (PRAME-A24)
The Company is 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. 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 IND/CTA submission in 2024.
IMC-M113V and IMC-I109V: aiming for functional cure in HIV and HBV
The Company is enrolling people living with HIV in the multiple ascending dose (MAD) part of a Phase 1 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.
In the ongoing Phase 1 trial with IMC-I109V, enrolling people living with HBV in the single ascending dose portion, the Company has amended the study to include HBV-positive hepatocellular carcinoma in the multiple ascending dose portion of the study.
Financial Results
Total net product revenue arising from the sale of KIMMTRAK was £45.5 million ($57.8 million) and £87.6 million (£111.3 million) in the three and six months ended June 30, 2023, respectively, of which £32.8 million ($41.7 million) and £62.3 million ($79.2 million) was in the United States, £12.2 million ($15.5 million) and £24.5 million ($31.2 million) was in Europe, and £0.5 million ($0.6 million) and £0.7 million ($0.9 million) was in the rest of the world. For the three and six months ended June 30, 2022, the Company recorded total net product and pre-product revenue of £27.7 million and £38.2 million, respectively.
For the three and six months ended June 30, 2023, the Company’s research and development expenses were £28.8 million ($36.6 million) and £57.2 million ($72.7 million), respectively, as compared to £20.2 million and £38.7 million for the three and six months ended June 30, 2022, respectively. For the three and six months ended June 30, 2023, the selling and administrative expenses were £33.9 million ($43.1 million) and £67.2 million ($85.4 million), respectively, compared to £18.8 million and £38.9 million for the three and six months ended June 30, 2022, respectively.
Basic and diluted loss per share for the three and six months ended June 30, 2023 was £0.29 ($0.37) and £0.64 ($0.81), respectively, compared to a basic and diluted loss per share of £0.14 and £0.51 for the three and six months ended June 30, 2022, respectively.
Cash and cash equivalents were £342.3 million ($435.1 million) as of June 30, 2023, compared to £332.5 million as of December 31, 2022.
We maintain our books and records in pounds sterling. For the convenience of the reader, we have translated pound sterling amounts as of and for the period ended June 30, 2023 into U.S. dollars at a rate of £1.00 to $1.2709.
Audio Webcast
Immunocore will host a conference call today, August 10, 2023 at 8:00 A.M. EDT/ 1:00 PM BST, to discuss the second quarter financial results and provide a business update. The call will also be available via webcast by visiting the Events & Presentations section on Immunocore’s website. A replay of this webcast will be available for 30 days.
Conference Call Details:
U.S. (toll-free): 877-405-1239
International (toll): +1 201-389-0851
Upcoming Investor Conference
H.C. Wainwright Immune Cell Engager Virtual Conference
Fireside Chat: Thursday, August 17, 2023, at 1:00 pm ET
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 country. 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 BICR, with secondary endpoints of overall survival (OS) and overall response rate (ORR).
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 ImmTAV molecules and infectious diseases
ImmTAV (Immune mobilizing monocolonal 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.