On August 10, 2022 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 its financial results for the second quarter ended June 30, 2022 and provided a business update (Press release, Immunocore, AUG 10, 2022, View Source [SID1234618008]).
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"The first half of 2022 has been one of robust execution, including delivering multiple KIMMTRAK commercial launches. In addition, in July, we executed a PIPE transaction with four of our largest shareholders, which allows us to accelerate the development of our early- and late-stage pipeline and extend our cash runway through 2025," commented Bahija Jallal, Chief Executive Officer of Immunocore. "The Immunocore team has pioneered the development from bench to bedside of the world’s first TCR treatment, which is now approved in over 30 countries. We are applying the learnings from KIMMTRAK to develop our other clinical-stage bispecific T cell engagers in oncology including ImmTACs targeting PRAME and MAGE-A4, and infectious disease ImmTAVs for HBV and HIV."
"The promising survival benefit for KIMMTRAK in metastatic cutaneous melanoma (mCM) has provided confidence to initiate a randomized Phase 2/3 trial in patients with previously treated, advanced melanoma," said David Berman, Head of Research & Development of Immunocore. "At IO-ESMO last year, we demonstrated that our ImmTAC platform against MAGE-A4 can deliver durable clinical responses in solid tumors. At ESMO (Free ESMO Whitepaper) this year, the first clinical data for an ImmTAC targeting PRAME, a protein broadly expressed in multiple solid tumors will be presented."
Second Quarter 2022 Highlights (including post-period)
KIMMTRAK (tebentafusp-tebn):
In April, the European Commission approved KIMMTRAK (tebentafusp) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). With this approval, KIMMTRAK has received marketing authorisation in all European Union (EU) member states and, following completion of related national procedures, KIMMTRAK will also be eligible for sale in Iceland, Liechtenstein, and Norway.
In April, KIMMTRAK was added as a recommended Category 1 treatment in the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for mUM. NCCN publishes evidence-based guidelines that are followed by many healthcare professionals in the United States and globally.
In May, the first patient in Germany was infused with KIMMTRAK, less than one week from price listing. The Company also successfully transitioned all patients (more than 50 patients) from the early access program (EAP) in Germany onto commercial supply in the month of May.
In June, the Company presented post-hoc analyses from its Phase 3 clinical trial of KIMMTRAK in mUM at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. In an analysis of the Phase 3 trial, an overall survival (OS) benefit observed for tebentafusp among mUM patients who have initial radiographic progression demonstrates that radiographic assessment underestimates the benefit. In another post hoc analysis of the Phase 3 trial, the vast majority of patients treated with tebentafusp (84%) either did not require corticosteroids (74%) or only received them on a single day (10%). Corticosteroid use following the pre-specified adverse event (AE) guidelines was not associated with any significant impact on efficacy of KIMMTRAK.
In June, KIMMTRAK, for the treatment of mUM, was added to the ASCO (Free ASCO Whitepaper) Rapid Recommendations Updates to the ASCO (Free ASCO Whitepaper) Guidelines. This recommendation was based on the Phase 3 trial and the FDA approval. Prior to this update, there were no recommendations by ASCO (Free ASCO Whitepaper) for any systemic therapy in uveal melanoma.
In June, the UK Medicines and Healthcare products Regulatory Agency (MHRA), Australian Therapeutic Goods Administration (TGA) and Health Canada approved KIMMTRAK for the treatment of HLA-A*02:01-positive adult patients with unresectable or mUM.
KIMMTRAK (tebentafusp) developmental programs:
In June, the Company announced a clinical trial collaboration and supply agreement with Sanofi to evaluate Sanofi’s product candidate SAR444245, non-alpha IL-2, in combination with KIMMTRAK in patients with mCM. Under the terms of the agreement, we provide KIMMTRAK at our own cost, and Sanofi is responsible for clinical development and will assume costs associated with the study.
In June, the Company presented updated clinical data from its Phase 1b clinical trial of tebentafusp in mCM in an oral presentation at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting. In combination with checkpoint inhibitors in mCM, the maximum target doses of tebentafusp (68 mcg) plus durvalumab (20 mg/kg) were well tolerated. In mCM patients who progressed on prior anti-PD(L)1, tebentafusp with durvalumab continues to demonstrate promising overall survival (OS) (1-yr ~75%) compared to recent benchmarks (1-yr ~55%).
Today, the Company announced its plans to evaluate tebentafusp in a randomized Phase 2/3 trial in previously treated advanced melanoma which was designed with input from global melanoma experts and from the US FDA. The trial will enroll patients with advanced melanoma, excluding uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase inhibitor (TKI). This population remains a significant unmet need where the preferred option is enrollment in clinical trials. Patients will be randomized to one of three arms including KIMMTRAK, as monotherapy or in combination with an anti-PD1, and a control arm. Patients randomized to the control arm will immediately enter overall survival (OS) follow-up where they may be treated per the investigator decision including other clinical trials. This innovative design effectively randomizes patients to "real world" treatment since clinical trials are the preferred option. The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of OS and circulating tumor DNA (ctDNA) reduction. The Phase 3 portion currently plans to enroll 170 patients per arm and has a primary endpoint of OS. The design of the Phase 3 trial—including lines of prior therapy, whether to discontinue an arm, and powering assumptions—may be adapted based on results from the Phase 2 portion. The Company plans to start the randomization of the trial in the fourth quarter of 2022.
IMC-F106C Targeting PRAME
The initial Phase 1 data from the dose escalation study of IMC-F106C, the first PRAME x CD3 ImmTAC bispecific protein, was accepted for proffered paper (oral presentation) during the "Investigational Immunotherapy" session on Friday, September 9, 2022, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in Paris, France. PRAME is overexpressed in many solid tumors including NSCLC, SCLC, endometrial, ovarian, melanoma and certain breast cancers. The company plans to report data from at least 20 PRAME positive and efficacy evaluable patients. Dr. Omid Hamid, Chief, Translational Research and Immunotherapy & Director, Melanoma Therapeutics, of The Angeles Clinic, will present the initial results from the Phase 1 study at 4:50 PM CEST. The company will also host an in-person and webcasted investor and analyst event at 6:30 PM CEST / 12:30 PM ET Friday, September 9th.
ImmTAV clinical programs:
In June, the Company presented data from the first three patients in the first-in-human clinical trial of IMC-I109V for chronic hepatitis B at the EASL International Liver Congress. IMC-I109V is designed to overcome T cell dysfunction by recruiting non-exhausted T cells to eliminate hepatocytes harbouring covalently closed circular DNA or integrated HBV DNA. Elimination of these cells is necessary to achieve a state of ‘functional cure’ defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. In this first cohort, the three patients received a single dose of 0.8 mcg, based on the minimum anticipated biological effect level (MABEL). The dose in this initial cohort was well tolerated and was not associated with adverse events and resulted in a transient, small decrease in serum HBsAg with concomitant minor increase in alanine transaminase (ALT).
In July, the Company dosed the first patient in the first-in-human clinical trial of IMC-M113V, a new class of bispecific protein immunotherapy that is being developed for the treatment of patients with human immunodeficiency virus (HIV) infection. IMC-M113V is an immunotherapeutic approach designed to specifically eliminate CD4+ cells that are persistently infected with HIV (‘reservoirs’). IMC-M113V targets a peptide derived from the Gag protein that is presented by HLA*A02 on the surface of HIV infected cells. Reduction of the number of these cells is one way to potentially achieve a state of viral suppression in the absence of anti-retroviral medications, or a ‘functional cure’.
Corporate and financial updates:
For the second quarter ended, June 30, 2022, Immunocore reported net KIMMTRAK / tebentafusp revenues of £27.7 million (or $33.7 million). U.S. net product revenue from the sale of KIMMTRAK in the second quarter was £18.1 million (or $22.1 million), Europe net product revenue from the sale of KIMMTRAK (primarily in Germany) was £5.9 million (or $7.1 million), and France net pre-product revenue from the sale of tebentafusp was £3.7 million (or $4.5 million).
In July, the Company announced a private investment in public equity ("PIPE") financing with four existing investors for net proceeds of $139.6 million. This financing, along with anticipated revenue from KIMMTRAK and cash and cash equivalents on hand, are expected to fund the Company through 2025.
In June, Siddharth (Sid) Kaul was appointed as a non-executive member of the Company’s Board of Directors and will serve as a member of the Audit and Remuneration committees. Sid is a seasoned finance professional with deep expertise within the life sciences industry. He retired as Group Treasurer and Head of Business Planning and Analysis at Novartis in 2021 after a 17-year career at the company, where his previous roles included serving as Novartis’ Chief Financial Officer, Pharma Europe and Chief Financial Officer, Pharma U.S.
Anticipated Upcoming Milestones
KIMMTRAK
Q4 2022 – start randomized Phase 2/3 clinical trial in previously treated advanced melanoma
ImmTAC pipeline
Q3 2022 – report initial data from IMC-F106C (PRAME) Phase 1 trial in multiple solid tumors at ESMO (Free ESMO Whitepaper) Congress 2022 in September
Q4 2022 – report complete data from IMC-C103C (MAGE-A4) Phase 1 trial in multiple solid tumors and initial data from ovarian expansion arm
Financial Results
Basic and diluted loss per share was £0.14 (or $0.17) and £0.51 (or $0.62) for the three and six months ended June 30, 2022, respectively, compared to £0.75 and £1.51 for the three and six months ended June 30, 2021, respectively. Total operating loss for the three and six months ended June 30, 2022 was £7.0 million (or $8.5 million) and £23.5 million (or $28.5 million), respectively, compared to £34.5 million and £66.4 million, respectively, for the same periods in 2021.
Total net product and net pre-product revenue arising from the sale of KIMMTRAK and tebentafusp was £27.7 million (or $33.7 million) in the three months ended June 30, 2022, and £38.2 million (or $46.5 million) in the six months ended June 30, 2022. In comparison, no product or pre-product revenue was recorded in these territories in the three and six months ended June 30, 2021. U.S. net product revenue from the sale of KIMMTRAK in the second quarter was £18.1 million (or $22.1 million), Europe net product revenue from the sale of KIMMTRAK (primarily in Germany) was £5.9 million (or $7.1 million), and France pre-product revenue from the sale of tebentafusp was £3.7 million (or $4.5 million).
For the three and six months ended June 30, 2022, our research and development expenses were £20.2 million (or $24.5 million) and £38.7 million (or $47.1 million), respectively, as compared to £16.5 million and £36.4 million for the three and six months ended June 30, 2021, respectively. For the three and six months ended June 30, 2022, our selling and administrative expenses were £18.8 million (or $22.9 million) and £38.9 million (or $47.3 million), respectively, compared to £23.8 million and £44.0 million for the three and six months ended June 30, 2021, respectively.
Cash and cash equivalents were £208.1 million or $253.0 million as of June 30, 2022 compared to £237.9 million as of December 31, 2021. We subsequently raised a further £116.7 million (or $140 million) in the July 2022 PIPE before deductions for estimated attributable expense of £0.3 million (or $0.4 million).
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, 2022 into U.S. dollars at a rate of £1.00 to $1.2162.
Audio Webcast
Immunocore will host a conference call today, August 10, 2022 at 8:00 A.M. EDT/ 1:00 PM BST, to discuss the second quarter 2022 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.
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 TEBE-AM Phase 2 /3 Trial
IMCgp100-203 is a randomized Phase 2/3 trial in previously treated advanced melanoma that will evaluate the overall survival (OS) of KIMMTRAK (tebentafusp). The trial will enroll patients with advanced melanoma that have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase inhibitor (TKI). The Phase 2/3 trial will randomize to one of three arms including KIMMTRAK, as monotherapy or in combination with an anti-PD1, and a control arm. Patients randomized to the control arm will immediately enter overall survival (OS) follow-up where they may be treated per the investigator decision including other clinical trials. This design effectively randomizes patients to "real world" treatment since clinical trials are the preferred option. The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of OS and circulating tumor DNA (ctDNA) reduction. The Phase 3 portion currently plans to enroll 170 patients per arm and has a primary endpoint of OS. However, the design of the Phase 3 including eligibility, whether to discontinue an arm and powering may be adapted based on results from the Phase 2 portion.
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.
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.