Immunocore announces the presentation of initial data from the Phase 1 ImmTAV® trial for chronic Hepatitis B at the EASL International Liver Congress™
IMC-I109V, T cell receptor bispecific, targets an envelope antigen
Single Ascending Dose portion of Phase 1 study to evaluate safety, antiviral activity, and pharmacokinetics
In the initial cohort, HBsAg declines and ALT elevations indicated that a single, very low dose of IMC-I109V elicited on-target activity, consistent with mechanism of action and without any adverse events
IMC-I109V is a TCR bispecific designed to specifically eliminate HBV-infected hepatocytes expressing hepatitis B surface antigen (HBsAg) via T cell redirection. 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. Since the mechanism results in hepatocyte lysis, transient liver enzyme increases are expected, necessitating a conservative dosing schedule in the Company’s first-in-human study of IMC-I109V.
In this first cohort, three patients each 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 were reported in any patient. The maximum serum concentrations of IMC-I109V were consistent with the dose level. By hour 12, serum concentrations declined below the lower limit of quantification. IL-6 cytokine levels increased within the first 24 hours in all three patients, which is consistent with the IMC-I109V mechanism of action. Small and transient increases in alanine transaminase (ALT), albeit within the normal range, were observed in the first few days after dosing, before returning to normal levels. In two of the three patients, serum HBsAg levels transiently decreased, with the same kinetics as ALT, by 11-15% during Days 3-15 post infusion, before returning to baseline within 3 weeks post-infusion.
“We designed our T cell receptor based bispecific proteins to harness the immune system to potentially achieve a functional cure for HBV,” said
The trial is an open label study evaluating the safety, antiviral activity, and pharmacokinetics of IMC-I109V in HLA-A*02:01 positive patients with chronic hepatitis B who are non-cirrhotic, HBeAg-negative and virally suppressed on nucleos(t)ide analogues. Part 1 is a single ascending dose to identify a safe and pharmacologically active dose. Part 2 is a multiple ascending dose to evaluate safety and anti-HBV activity of repeated doses over 24 weeks.
About ImmTAV molecules and infectious diseases
ImmTAV (Immune mobilising monocolonal 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.
Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding: the therapeutic potential of IMC-I109V to be an effective treatment for patients with HBV; the expected clinical benefits of IMC-I109V including its potential as a “functional cure”; anticipated results from the Phase 2 portion of the clinical trial of IMC-I109V and expectations regarding the ability to recruit and enroll additional patients in the clinical trial of IMC-I109V. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, the impact of the ongoing COVID-19 pandemic and the Omicron variant on the Company’s business, strategy clinical trials and financial position; Immunocore’s ability to maintain regulatory approval of KIMMTRAK; its ability to execute its commercialization strategy for KIMMTRAK including the timing or likelihood of expansion into additional markets or geographies; its ability to develop, manufacture and commercialize its other product candidates; commercial supply of KIMMTRAK or any future approved products, and launching, marketing and selling of KIMMTRAK or any future approved products; Immunocore’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK in
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Source: Immunocore Holdings Limited