Immunocore Highlights Phase 1 Data for Hepatitis B Candidate
IMC-I109V shows a manageable safety profile and promising antiviral activity.
Immunocore Holdings plc (NASDAQ: IMCR), a leading biotechnology company, recently shared key data from its Phase 1 trial of IMC-I109V, a groundbreaking bispecific T cell receptor therapy targeting hepatitis B. This innovative treatment aims to address hepatitis B by selectively eliminating infected liver cells presenting hepatitis B surface antigen (HBsAg).
The reported results, showcased at The Liver Meeting, organized by the American Association for the Study of Liver Diseases, reveal that IMC-I109V is well-tolerated across various dosage levels and demonstrates pharmacodynamic (PD) activity that aligns with its intended mechanism. This includes a significant reduction in HBsAg levels, which is crucial for determining a resolved hepatitis B infection.
Promising Results and Mechanism of Action
David Berman, Head of Research and Development, expressed optimism regarding the findings, stating, “The promising decrease in serum HBsAg following a single dose of IMC-I109V highlights the potential of T cell receptor-based therapy for chronic HBV infection.” He noted that these results, coupled with previous success seen with their ImmTAV candidate for HIV, further affirm the platform's capability to achieve functional cures for challenging infectious diseases.
The trial enrolled 20 individuals, who were administered ascending doses (0.8 mcg, 2.4 mcg, 7 mcg, and 20 mcg) of IMC-I109V via IV infusion on the first day. Each dose underwent rigorous assessment to evaluate both tolerability and therapeutic activity as determined by specific PD endpoints, such as a predefined increase in levels of immune markers.
Observations and Patient Safety
In the trial, doses of 7 mcg and above demonstrated consistent pharmacodynamic activity, notably a dose-dependent reduction in HBsAg levels, which showed a clear nadir around day 8 post-infusion. Four participants reached the beneficial threshold of a ? 0.2 log10 IU/ml reduction in their serum HBsAg levels, with three maintaining these lower levels throughout the follow-up period. These promising outcomes correlate with additional markers of immune activation, such as IL-6 and ALT elevations, which occurred as anticipated based on the treatment mechanism.
While treatment-related adverse events (TRAEs) were noted in eight participants, they were predominantly mild and resolved swiftly. In particular, transient systemic symptoms were observed within 24 hours post-infusion, and any elevations in ALT decreased within 14 days. Bilirubin and prothrombin levels stayed within healthy ranges throughout the study duration.
Cytokine Release Syndrome and Safety Measures
During the 20 mcg cohort, one participant experienced Grade 2 cytokine release syndrome but responded well to supportive care and corticosteroids, showcasing the management strategies in place for any potential adverse effects. Following this event, additional precautions were implemented for subsequent participants receiving the same dosage, resulting in no serious adverse events.
IMC-I109V's design aims to alleviate HBV-specific T cell exhaustion by efficiently mobilizing non-exhausted T cells to target and eliminate hepatocytes containing the virus's DNA.
Immunocore believes the promising early-phase findings of HBsAg reduction via this novel therapeutic approach underscore the need for further exploration of IMC-I109V through various dosing strategies.
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About ImmTAV Molecules for Infectious Diseases
ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules represent a pioneering class of bispecific therapies designed to empower the immune response against viral infections. Immunocore is proactively furthering candidates aimed at curing patients with both HIV and hepatitis B, aspiring to achieve sustained control over these infections even after ceasing antiviral therapy.
Overview of Immunocore
Immunocore is at the forefront of biotechnology, creating a revolutionary class of TCR bispecific immunotherapies called ImmTAX, developed to address a wide array of medical conditions including cancer, autoimmune issues, and infectious diseases. With their proprietary platform, the company is building an extensive pipeline that encompasses numerous active clinical and pre-clinical initiatives, specifically targeting oncology and infectious diseases. Their leading therapy, KIMMTRAK, has gained approval for treating HLA-A*02:01-positive adult patients with advanced uveal melanoma across several major markets.
Frequently Asked Questions
What is IMC-I109V?
IMC-I109V is a bispecific T cell receptor therapy designed to target and eliminate hepatitis B virus-infected liver cells.
What did the Phase 1 trial reveal about IMC-I109V?
The trial showed that IMC-I109V is generally well tolerated and exhibits promising antiviral activity, including reductions in HBsAg levels.
How many patients were involved in the trial?
The Phase 1 trial enrolled 20 participants, who received ascending doses of IMC-I109V.
What are ImmTAV molecules?
ImmTAV molecules are bispecific therapies aimed at enhancing the immune system’s ability to identify and eliminate virally infected cells.
What is Immunocore’s goal with HBV treatment?
Immunocore aims to achieve a sustained loss of viral antigens and markers in patients after stopping medication, targeting a functional cure for chronic HBV.
