On June 3, 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, infection and autoimmune disease, reported it has entered into a clinical trial collaboration and supply agreement with Sanofi (Press release, Immunocore, JUN 3, 2022, View Source [SID1234615493]).
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Under the agreement, Sanofi will evaluate its precisely PEGylated, engineered version of IL-2, SAR444245, in combination with KIMMTRAK, Immunocore’s novel bispecific protein targeting gp100, in HLA-A*02:01 positive patients with advanced unresectable or metastatic skin cancers as part of Sanofi’s ongoing Phase 1/2 study.
Under the terms of the agreement, Sanofi will be responsible for clinical development and will assume all costs associated with the study, other than expenses related to the manufacturing and supply of KIMMTRAK for which Immunocore is responsible.
SAR444245 (formerly known as THOR-707), Sanofi’s product candidate, is a differentiated IL-2 engineered for specificity and selectivity towards CD8+ T cells and Natural Killer (NK) cells. The molecule has a single, targeted PEG-moiety irreversibly linked to a novel amino acid inserted at a precise location. This characteristic prevents SAR444245 from binding to CD25 (alpha-subunit) while preferentially binding to the beta/gamma IL-2 receptor subunits. Beta/gamma IL-2 receptor engagement has tuned IL-2 specificity for the robust proliferation of T-effector and NK cells, avoiding expansion of T-regulatory cells or eosinophils.
John Reed, MD, PhD, Executive Vice President and Global Head of R&D of Sanofi, said: "We are excited to embark on this collaboration with Immunocore. The strong scientific rationale makes it compelling to investigate Immunocore’s KIMMTRAK, the first approved TCR therapeutic for a solid tumor, in combination with our engineered lymphokine, SAR444245. While we are actively studying SAR444245 as monotherapy and in combination with anti-PD-1 class checkpoint inhibitors and with approved immuno-competent monoclonal antibodies, the collaboration with Immunocore represents Sanofi’s first exploration of combining SAR444245 with a T cell engager. We are therefore very eager to explore this high potential combination in our ongoing multi-arm Phase 1/2 clinical study."
David Berman, MD, PhD, Head of Research and Development at Immunocore, said: "Immunocore has demonstrated that in vitro, IL-2 can enhance the activity of the ImmTAC platform, particularly in the context of tumor-associated inhibitory macrophages, and that metastatic uveal melanoma (mUM) patients with higher expression of IL2-beta and gamma, but not alpha, receptor have better overall survival (OS) on KIMMTRAK (presented at SITC (Free SITC Whitepaper) 2021). We are pleased that Sanofi will test this hypothesis in their clinical trial in patients with metastatic cutaneous melanoma (mCM), a population with significant unmet medical need."
In January 2022 and April 2022, the United States Food and Drug Administration (FDA) and the European Commission (EC), respectively, approved KIMMTRAK (tebentafusp) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Immunocore is currently planning a randomized study of KIMMTRAK with or without anti-PD1 therapy in patients with metastatic melanoma and anticipates initiating the trial in the fourth quarter of 2022.
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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 granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the United States, Accelerated Assessment by the EMA, and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma.
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.
Please see full 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.
About ImmTAC Molecules
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.