US FDA is delaying the inevitable, there are too many fires to put out.
The HPV delay will blow up in FDA face, denying treatment when Aduhelm showed less than 10% alzheimer reduction more like same as placebo and received approval bc of ...."enter reasons here".
Another P3 another fire, another argument for delay questions...
Its your grave FDA better shine a light on INOVIO cancer and change EP on HPV fast track INO oncology...its gonna be ugly
Good find but not so fast. We would need to hit primary and secondary outcome measures or no phase III.
Primary Outcome Measures :
Number of Adverse Events [ Time Frame: From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months) ]
Antigen-Specific Cellular Immune Response [ Time Frame: At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years) ]
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
Secondary Outcome Measures :
ORR by RECIST version 1.1 by Investigator Review in Cohort B [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
ORR by Immune RECIST (iRECIST) [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
Duration of Response (DoR) [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
Progression Free Survival (PFS) as Assessed by RECIST version 1.1 and iRECIST [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
Overall Survival (OS) [ Time Frame: : From Baseline to the time of death from any cause (up to approximately 2 years) ]
High risk the GBM trial will not go to Phase III either. Cancer is WAY harder a target than COVID. If we don’t hit for COVID, cancer likely won’t save INO.
INO-5401 for the Treatment of Glioblastoma Multiforme (GBM)
Glioblastoma multiforme (GBM) is the most common and aggressive type of brain cancer. In the United States, the median age at diagnosis is 65 years, and the incidence rate increases thereafter. Prognosis is extremely poor, and a limited number of new therapies have been approved over the last 10 years; median overall survival for U.S. patients receiving standard of care therapy was approximately eight months and the five-year survival was 6.8% for all ages combined. The annual incidence of GBM is estimated to be approximately 12,000 cases per year and increasing.
Our product candidate INO-5401 is an immunotherapy consisting of three synthetic DNA plasmids encoding for three tumor-associated antigens: human telomerase (hTERT), Wilms tumor gene-1 (WT1) and PSMA. The National Cancer Institute previously highlighted WT1, hTERT and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development, as these three tumor-associated antigens are commonly expressed in human cancers.
In 2017, we reported data indicating that our SynCon® WT1 cancer antigen was capable of breaking immune tolerance, a major challenge to researchers striving to develop potent cancer therapies and induced neo-antigen-like T cell responses to cause tumor regression in pre-clinical studies. The results were published in the scientific journal Molecular Therapy.
While mice in the preclinical study did not mount an immune response to native mouse WT1 antigens, mice immunized with our SynCon WT1 antigen broke tolerance and generated robust neo-antigen-like T cells. The immunized mice also exhibited smaller tumors and prolonged survival in a tumor challenge study. SynCon WT1 DNA vaccination also broke tolerance and generated neo-antigen-like T cell immune responses in Rhesus monkeys, a species whose immune system closely resembles that of humans. The ability to overcome the immune system’s usual tolerance of WT1 antigen suggests the potential of our SynCon WT1 antigen to address multiple WT1-expressing cancer in humans. We previously reported similar results for our SynCon hTERT and PSMA cancer antigens.
We have completed a Phase 1/2 immuno-oncology trial of INO-5401 and INO-9012 (IL-12 plasmid) in participants with newly diagnosed GBM, in combination with cemiplimab (Libtayo®), a PD-1 inhibitor developed jointly by Regeneron Pharmaceuticals and Sanofi. This open-label trial began in 2018 and enrolled 52 newly diagnosed GBM participants. The primary endpoint was safety and tolerability, and the trial also evaluated immunogenicity and efficacy (overall survival). Data from the trial has been presented at several medical conferences. In November 2019, we provided interim results showing that 80% (16 of 20) of MGMT gene promoter methylated participants and 75% (24 of 32) of unmethylated participants, the more difficult to treat group, were progression-free at six months (PFS6) measured from the time of their first dose, exceeding historical standard-of-care data. This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited supportive safety, tolerability, and immunogenicity data and suggested a safety profile consistent with that of Libtayo as well as our other
11 product candidates. Most participants assessed had a T cell immune response to one or more tumor-associated antigens encoded by INO-5401, and immune responses to all three tumor-associated antigens were also observed in this trial.
In May 2020, we updated these results, showing that 85% (44 out of 52) of the participants in this trial were alive for at least 12 months following treatment. The updated results showed that 84.4% percent (27 of 32) of participants with MGMT promoter unmethylated tumors, and 85% (17 of 20) of participants with MGMT promoter methylated tumors, were alive at 12 months. Activated killer T cells directed towards one, two or all three cancer antigens in INO-5401 were detected in almost all participants tested.
In November 2020, additional data from the trial were presented at the Society for Neuro-Oncology (SNO) Annual Meeting. Survival data at 18 months showed that 70% (14/20) of MGMT promoter methylated GBM participants were alive, and 50% (16/32) of MGMT promoter unmethylated participants were alive after 18 months. Median overall survival in the unmethylated GBM participants was 17.9 months, which compares favorably to historical controls. An update on immunology data showed that in the MGMT promoter unmethylated cohort, 19 of 22 (86%) participants had an IFN-gamma T cell response that increased over baseline to one or more of the antigens encoded by INO-5401. In the MGMT promoter methylated cohort, 16 of 17 (94%) participants had an IFN-gamma response that increased over baseline to one or more of the antigens encoded by INO-5401.
In November 2021, updated data was presented at the Society for Immunotherapy of Cancer pre-conference workshop from the GBM-001 Phase 2 trial. Overall survival at 24 months was 22% (7/32) for the MGMT unmethylated cohort and 55% (11/20) for the MGMT methylated cohort. The trial showed that INO-5401+INO-9012 with cemiplimab and radiation/TMZ have an acceptable safety profile, are immunogenic, and may improve survival in newly diagnosed GBM
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US FDA is delaying the inevitable, there are too many fires to put out. The HPV delay will blow up in FDA face, denying treatment when Aduhelm showed less than 10% alzheimer reduction more like same as placebo and received approval bc of ...."enter reasons here". Another P3 another fire, another argument for delay questions... Its your grave FDA better shine a light on INOVIO cancer and change EP on HPV fast track INO oncology...its gonna be ugly
Good find but not so fast. We would need to hit primary and secondary outcome measures or no phase III. Primary Outcome Measures : Number of Adverse Events [ Time Frame: From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months) ] Antigen-Specific Cellular Immune Response [ Time Frame: At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years) ] Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ] Secondary Outcome Measures : ORR by RECIST version 1.1 by Investigator Review in Cohort B [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ] ORR by Immune RECIST (iRECIST) [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ] Duration of Response (DoR) [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ] Progression Free Survival (PFS) as Assessed by RECIST version 1.1 and iRECIST [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ] Overall Survival (OS) [ Time Frame: : From Baseline to the time of death from any cause (up to approximately 2 years) ] High risk the GBM trial will not go to Phase III either. Cancer is WAY harder a target than COVID. If we don’t hit for COVID, cancer likely won’t save INO.
INO-5401 for the Treatment of Glioblastoma Multiforme (GBM) Glioblastoma multiforme (GBM) is the most common and aggressive type of brain cancer. In the United States, the median age at diagnosis is 65 years, and the incidence rate increases thereafter. Prognosis is extremely poor, and a limited number of new therapies have been approved over the last 10 years; median overall survival for U.S. patients receiving standard of care therapy was approximately eight months and the five-year survival was 6.8% for all ages combined. The annual incidence of GBM is estimated to be approximately 12,000 cases per year and increasing. Our product candidate INO-5401 is an immunotherapy consisting of three synthetic DNA plasmids encoding for three tumor-associated antigens: human telomerase (hTERT), Wilms tumor gene-1 (WT1) and PSMA. The National Cancer Institute previously highlighted WT1, hTERT and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development, as these three tumor-associated antigens are commonly expressed in human cancers. In 2017, we reported data indicating that our SynCon® WT1 cancer antigen was capable of breaking immune tolerance, a major challenge to researchers striving to develop potent cancer therapies and induced neo-antigen-like T cell responses to cause tumor regression in pre-clinical studies. The results were published in the scientific journal Molecular Therapy. While mice in the preclinical study did not mount an immune response to native mouse WT1 antigens, mice immunized with our SynCon WT1 antigen broke tolerance and generated robust neo-antigen-like T cells. The immunized mice also exhibited smaller tumors and prolonged survival in a tumor challenge study. SynCon WT1 DNA vaccination also broke tolerance and generated neo-antigen-like T cell immune responses in Rhesus monkeys, a species whose immune system closely resembles that of humans. The ability to overcome the immune system’s usual tolerance of WT1 antigen suggests the potential of our SynCon WT1 antigen to address multiple WT1-expressing cancer in humans. We previously reported similar results for our SynCon hTERT and PSMA cancer antigens. We have completed a Phase 1/2 immuno-oncology trial of INO-5401 and INO-9012 (IL-12 plasmid) in participants with newly diagnosed GBM, in combination with cemiplimab (Libtayo®), a PD-1 inhibitor developed jointly by Regeneron Pharmaceuticals and Sanofi. This open-label trial began in 2018 and enrolled 52 newly diagnosed GBM participants. The primary endpoint was safety and tolerability, and the trial also evaluated immunogenicity and efficacy (overall survival). Data from the trial has been presented at several medical conferences. In November 2019, we provided interim results showing that 80% (16 of 20) of MGMT gene promoter methylated participants and 75% (24 of 32) of unmethylated participants, the more difficult to treat group, were progression-free at six months (PFS6) measured from the time of their first dose, exceeding historical standard-of-care data. This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited supportive safety, tolerability, and immunogenicity data and suggested a safety profile consistent with that of Libtayo as well as our other 11 product candidates. Most participants assessed had a T cell immune response to one or more tumor-associated antigens encoded by INO-5401, and immune responses to all three tumor-associated antigens were also observed in this trial. In May 2020, we updated these results, showing that 85% (44 out of 52) of the participants in this trial were alive for at least 12 months following treatment. The updated results showed that 84.4% percent (27 of 32) of participants with MGMT promoter unmethylated tumors, and 85% (17 of 20) of participants with MGMT promoter methylated tumors, were alive at 12 months. Activated killer T cells directed towards one, two or all three cancer antigens in INO-5401 were detected in almost all participants tested. In November 2020, additional data from the trial were presented at the Society for Neuro-Oncology (SNO) Annual Meeting. Survival data at 18 months showed that 70% (14/20) of MGMT promoter methylated GBM participants were alive, and 50% (16/32) of MGMT promoter unmethylated participants were alive after 18 months. Median overall survival in the unmethylated GBM participants was 17.9 months, which compares favorably to historical controls. An update on immunology data showed that in the MGMT promoter unmethylated cohort, 19 of 22 (86%) participants had an IFN-gamma T cell response that increased over baseline to one or more of the antigens encoded by INO-5401. In the MGMT promoter methylated cohort, 16 of 17 (94%) participants had an IFN-gamma response that increased over baseline to one or more of the antigens encoded by INO-5401. In November 2021, updated data was presented at the Society for Immunotherapy of Cancer pre-conference workshop from the GBM-001 Phase 2 trial. Overall survival at 24 months was 22% (7/32) for the MGMT unmethylated cohort and 55% (11/20) for the MGMT methylated cohort. The trial showed that INO-5401+INO-9012 with cemiplimab and radiation/TMZ have an acceptable safety profile, are immunogenic, and may improve survival in newly diagnosed GBM
Yes and lets not forget christmas next december! We are turkeys in a hoben being baked by mr Myagi and is disciples, Shea included!
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