ICOSL vIgD / Vertex - LARVOL DELTA

[VIRTUAL] Alpn-101 (ICOSL vIgD-Fc), a Dual Antagonist of the ICOS and CD28 Costimulatory Pathways, for Treatment of Steroid Refractory Acute Gvhd (aGVHD): Case Report (TCT-ASTCT-CIBMTR 2021) - P1 | "A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants..."

Clinical • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Mucositis • Myelodysplastic Syndrome • Oncology • Oral Cancer • Squamous Cell Carcinoma • Thrombocytopenia • Tongue Carcinoma • Transplantation • ICOS

[VIRTUAL] Alpn-101 (ICOSL vIgD-Fc), a Dual Antagonist of the ICOS and CD28 Costimulatory Pathways, for Treatment of Steroid Refractory Acute Gvhd (aGVHD): Case Report (TCT-ASTCT-CIBMTR 2021) - P1 | "A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants..."

Clinical • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Mucositis • Myelodysplastic Syndrome • Oncology • Oral Cancer • Squamous Cell Carcinoma • Thrombocytopenia • Tongue Carcinoma • Transplantation • ICOS

[VIRTUAL] Alpn-101 (ICOSL vIgD-Fc), a Dual Antagonist of the ICOS and CD28 Costimulatory Pathways, for Treatment of Steroid Refractory Acute Gvhd (aGVHD): Case Report (TCT-ASTCT-CIBMTR 2021) - P1 | "A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants..."

Clinical • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Mucositis • Myelodysplastic Syndrome • Oncology • Oral Cancer • Squamous Cell Carcinoma • Thrombocytopenia • Tongue Carcinoma • Transplantation • ICOS

[VIRTUAL] Alpn-101 (ICOSL vIgD-Fc), a Dual Antagonist of the ICOS and CD28 Costimulatory Pathways, for Treatment of Steroid Refractory Acute Gvhd (aGVHD): Case Report (TCT-ASTCT-CIBMTR 2021) - P1 | "A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants..."

Clinical • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Mucositis • Myelodysplastic Syndrome • Oncology • Oral Cancer • Squamous Cell Carcinoma • Thrombocytopenia • Tongue Carcinoma • Transplantation • ICOS

[VIRTUAL] Alpn-101 (ICOSL vIgD-Fc), a Dual Antagonist of the ICOS and CD28 Costimulatory Pathways, for Treatment of Steroid Refractory Acute Gvhd (aGVHD): Case Report (TCT-ASTCT-CIBMTR 2021) - P1 | "A 69-year-old male with a history of successful chemoradiation for stage 4 HPV+ squamous cell carcinoma of the tongue developed secondary myelodysplastic syndrome that failed azacitidine. He received an 11/12 HLA-matched, unrelated peripheral blood stem cell graft after conditioning with fludarabine and melphalan, with neutrophil engraftment by day +28...The post-transplant course was complicated by severe mucositis, difficult oral intake and aspiration leading to PEG tube placement, and biopsy-confirmed lower intestinal tract GVHD diagnosed on day +54 that was refractory to 5 lines of therapy, including high dose methylprednisolone, budesonide and ruxolitinib...The course suggests that GVHD responded briskly to a single dose of ALPN-101 following failure of 5 lines of therapy, despite withdrawal of tacrolimus and an abrupt steroid taper, and prior to the potentially confounding addition of eculizumab. Dual inhibition of CD28 and ICOS, such as by ALPN-101, warrants..."

Clinical • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Mucositis • Myelodysplastic Syndrome • Oncology • Oral Cancer • Squamous Cell Carcinoma • Thrombocytopenia • Tongue Carcinoma • Transplantation • ICOS

[VIRTUAL] A DOUBLE BLIND, PLACEBO CONTROLLED, SINGLE ASCENDING DOSE (SAD) AND MULTIPLE ASCENDING DOSE (MAD) STUDY OF ALPN-101, A FIRST-IN-CLASS DUAL ICOS/CD28 ANTAGONIST, IN HEALTHY VOLUNTEERS (HV) (EULAR 2020) - P1 | "Background: ALPN-101 (ICOSL vIgD-Fc) is an Fc fusion protein of a human inducible T cell costimulatory ligand (ICOSL) variant immunoglobulin domain (vIgD™) designed to inhibit simultaneously the CD28 and ICOS inflammation pathways (1). ALPN-101 was well tolerated when administered as single doses up to 10 mg/kg or as repeated doses of up to 1 mg/kg weekly for 4 weeks, exhibiting dose-dependent PK, TS and PD including the inhibition of antibody responses to KLH immunization. These findings support future studies to evaluate the efficacy of ALPN-101 in multiple rheumatic and other inflammatory diseases."

Clinical • Immune Modulation • Immunology • Inflammation • Lupus • Rheumatology • CD8

Therapeutic Candidate ALPN-101, a Dual ICOS/ CD28 Antagonist, Demonstrates In Vivo Efficacy in an Experimental Autoimmune Encephalomyelitis (EAE) Model (ANA 2018) - " We used our proprietary technology platform to create a tailored ICOSL vIgD-Fc fusion protein (ALPN-101) capable of binding both ICOS and CD28 with high affinity and inhibiting their T cell costimulatory pathways. ALPN-101 is capable of delivering dual inhibitory signals to T cell co-stimulators CD28 and ICOS, which may therapeutically translate to diminishing the severity of autoimmune and inflammatory diseases. ALPN-101 has demonstrated activity in the EAE model, a commonly used experimental model for multiple sclerosis. The efficacy of ALPN-101 appears superior to wild-type ICOSL-Fc domains in this model, presumably due to its ability to bind the cognate ligand ICOS with enhanced affinity and to bind the additional counter-structure CD28."

Preclinical • CNS Disorders • Multiple Sclerosis

Alpn-101, a Dual ICOS/CD28 Antagonist, Demonstrates Potent and Dose-Dependent Suppression of Graft Vs. Host Disease (GvHD) in a Human/NSG Mouse Xenograft Model, with Activity Superior to CD28 or ICOS Single Pathway Antagonists (TCT-ASBMT-CIBMTR 2019) - "Background: ALPN-101 (ICOSL vIgD-Fc) is an Fc fusion protein of a human ICOSL variant immunoglobulin domain (vIgD) designed to simultaneously inhibit the ICOS and CD28 costimulatory pathways... A dose ranging study was conducted with 20, 100, or 500 g ALPN-101 administered to NSG mice engrafted with human PBMC, and compared to belatacept, an approved CTLA-4-Fc protein CD28 pathway inhibitor... ALPN-101 is a potent dual ICOS/CD28 T cell antagonist capableeven with a single doseof inhibiting lethal inflammatory processes with superior efficacy vs continuous CD28 or ICOS single pathway inhibition despite lower PK exposure, likely attributable to superior control of ICOS+ T cells which otherwise escape single pathway blockade. ALPN-101 is thus a promising novel therapeutic candidate for GvHD, and upcoming clinical trials will explore its therapeutic potential in GVHD and other inflammatory diseases."

Preclinical