Data from the single ascending dose part of the Phase 1 trial shows IMC-M113V is well tolerated
Expected markers of T cell activation observed in half of participants at 15-mcg dose; plasma viral load remained suppressed throughout dosing and follow-up
The multiple ascending dose part of the trial is enrolling participants to identify safety and anti-viral activity
OXFORDSHIRE, UK & CONSHOHOCKEN, PA & ROCKVILLE, MD, USA I February 22, 2023 I 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, autoimmune and infectious diseases, has presented at the Conference on Retroviruses and Opportunistic Infection (CROI) the first safety and activity data with IMC-M113V, a bispecific soluble TCR therapy built on Immunocore’s ImmTAX® technology which is being developed for the treatment of people living with HIV (PLWH).
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 in 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.’
“IMC-M113V, which is designed to redirect T cells to eliminate HIV-infected cells, was well tolerated at doses where we observed biomarkers of T cell engagement,” said David Berman, Head of R&D of Immunocore. “We are now enrolling people living with HIV in the multiple ascending dose part of the trial where we will evaluate the active dosing schedules that could lead to functional cure.”
Dr Linos Vandekerckhove, Laboratory director, HIV Cure Research Center, University Hospital Ghent, Belgium, said: “HIV continues to be a huge global health challenge. Although people living with HIV can control their disease with antiretroviral therapies, lifelong treatment is needed as reservoirs of HIV infected cells persist. If a functional cure could be found this could significantly transform treatment of this chronic infectious disease and decrease stigma of HIV.”
Initial Phase 1 trial data
In the single ascending dose part of the trial, three dose levels of IMC-M113V, given as a single IV infusion, were evaluated: a starting dose of 1.6 mcg, based on the minimum anticipated biological effect level (n=1), 5 mcg (n=1) and 15 mcg (n=10). All doses were well tolerated. There were no serious adverse events, significant changes in hematology or chemistry, nor cytokine release syndrome or neurotoxicity.
Plasma viral load remained suppressed throughout dosing and follow-up. In addition, transient, dose-dependent increases in serum IL6 occurred 8-24 hours post-infusion. Five out of the ten participants who received the 15-mcg dose showed a >4-fold rise in IL6, which had been prespecified as indicative of pharmacodynamic activity based on prior experience from clinical trials with KIMMTRAK (tebentafusp), the Company’s first ImmTAX therapy now approved for the treatment of metastatic or unresectable uveal melanoma.
Enrollment underway in next part of the trial
The Company has started enrolling people living with HIV in the multiple ascending dose (MAD) part of the trial, to identify a safe and tolerable dosing schedule that could lead to reduction in the viral reservoir and control of HIV after stopping antiretroviral therapies (ART), or functional cure. The MAD trial will enroll up to 28 participants.
About the STRIVE (Soluble T cell Receptors In Virus Eradication) trial
The STRIVE trial (IMC-M113V-101) is a first-in-human, open-label Phase 1/2 trial, designed to identify a safe and biologically active dose in HLA-A*02:01 positive PLWH receiving suppressive ART for ≤7 years. The trial’s secondary objectives are to characterize pharmacokinetic (PK) and pharmacodynamic (PD) profiles, including serum cytokines (IL2, IL6, IL8, IL10, IFNγ, TNFα, and IP10) pre- and ≤24 hours post-dosing. A ≥4-fold rise in IL6 was prespecified as indicative of PD activity.
People living with HIV can remain healthy with antiretroviral therapies, but they must continue to take medication for life as virus reservoirs remain. 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-A*02 on the surface of HIV infected cells.
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 Immunocore
Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune, and infectious disease. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including five clinical stage programs in oncology and infectious disease, advanced pre-clinical programs in autoimmune disease and multiple earlier pre-clinical programs. The Company’s most advanced oncology TCR therapeutic, 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.
SOURCE: Immunocore
Post Views: 367
Data from the single ascending dose part of the Phase 1 trial shows IMC-M113V is well tolerated
Expected markers of T cell activation observed in half of participants at 15-mcg dose; plasma viral load remained suppressed throughout dosing and follow-up
The multiple ascending dose part of the trial is enrolling participants to identify safety and anti-viral activity
OXFORDSHIRE, UK & CONSHOHOCKEN, PA & ROCKVILLE, MD, USA I February 22, 2023 I 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, autoimmune and infectious diseases, has presented at the Conference on Retroviruses and Opportunistic Infection (CROI) the first safety and activity data with IMC-M113V, a bispecific soluble TCR therapy built on Immunocore’s ImmTAX® technology which is being developed for the treatment of people living with HIV (PLWH).
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 in 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.’
“IMC-M113V, which is designed to redirect T cells to eliminate HIV-infected cells, was well tolerated at doses where we observed biomarkers of T cell engagement,” said David Berman, Head of R&D of Immunocore. “We are now enrolling people living with HIV in the multiple ascending dose part of the trial where we will evaluate the active dosing schedules that could lead to functional cure.”
Dr Linos Vandekerckhove, Laboratory director, HIV Cure Research Center, University Hospital Ghent, Belgium, said: “HIV continues to be a huge global health challenge. Although people living with HIV can control their disease with antiretroviral therapies, lifelong treatment is needed as reservoirs of HIV infected cells persist. If a functional cure could be found this could significantly transform treatment of this chronic infectious disease and decrease stigma of HIV.”
Initial Phase 1 trial data
In the single ascending dose part of the trial, three dose levels of IMC-M113V, given as a single IV infusion, were evaluated: a starting dose of 1.6 mcg, based on the minimum anticipated biological effect level (n=1), 5 mcg (n=1) and 15 mcg (n=10). All doses were well tolerated. There were no serious adverse events, significant changes in hematology or chemistry, nor cytokine release syndrome or neurotoxicity.
Plasma viral load remained suppressed throughout dosing and follow-up. In addition, transient, dose-dependent increases in serum IL6 occurred 8-24 hours post-infusion. Five out of the ten participants who received the 15-mcg dose showed a >4-fold rise in IL6, which had been prespecified as indicative of pharmacodynamic activity based on prior experience from clinical trials with KIMMTRAK (tebentafusp), the Company’s first ImmTAX therapy now approved for the treatment of metastatic or unresectable uveal melanoma.
Enrollment underway in next part of the trial
The Company has started enrolling people living with HIV in the multiple ascending dose (MAD) part of the trial, to identify a safe and tolerable dosing schedule that could lead to reduction in the viral reservoir and control of HIV after stopping antiretroviral therapies (ART), or functional cure. The MAD trial will enroll up to 28 participants.
About the STRIVE (Soluble T cell Receptors In Virus Eradication) trial
The STRIVE trial (IMC-M113V-101) is a first-in-human, open-label Phase 1/2 trial, designed to identify a safe and biologically active dose in HLA-A*02:01 positive PLWH receiving suppressive ART for ≤7 years. The trial’s secondary objectives are to characterize pharmacokinetic (PK) and pharmacodynamic (PD) profiles, including serum cytokines (IL2, IL6, IL8, IL10, IFNγ, TNFα, and IP10) pre- and ≤24 hours post-dosing. A ≥4-fold rise in IL6 was prespecified as indicative of PD activity.
People living with HIV can remain healthy with antiretroviral therapies, but they must continue to take medication for life as virus reservoirs remain. 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-A*02 on the surface of HIV infected cells.
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 Immunocore
Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune, and infectious disease. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including five clinical stage programs in oncology and infectious disease, advanced pre-clinical programs in autoimmune disease and multiple earlier pre-clinical programs. The Company’s most advanced oncology TCR therapeutic, 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.
SOURCE: Immunocore
Post Views: 367
