acazicolcept (ALPN-101) / Alpine Immune Sci, AbbVie - LARVOL DELTA

ALPN-101 (Acazicolcept) in Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=76 | Completed | Sponsor: Alpine Immune Sciences, Inc. | Active, not recruiting ➔ Completed | N=130 ➔ 76 | Trial completion date: Jan 2025 ➔ Jul 2024 | Trial primary completion date: Nov 2024 ➔ Jul 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

ALPN-101 (Acazicolcept) in Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=130 | Active, not recruiting | Sponsor: Alpine Immune Sciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

ALPN-101 (Acazicolcept) in Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Alpine Immune Sciences, Inc.

Trial completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN-101) Reveals Non-Redundant Roles of T Cell Co-Stimulation Pathways in Systemic Lupus Erythematosus (ACR Convergence 2023) - P2 | " HD or SLE PBMCs were stimulated with artificial antigen presenting cells expressing CD80, CD86, ICOSL and anti-CD3 (OKT3) for 48h with 100 nM of Fc control protein, acazicolcept, or comparators directed against CD28 (abatacept, [CTLA-4-Ig]) or ICOS (prezalumab [anti-ICOSL mAb]) or combined abatacept/prezalumab. Taken together, these and previous findings indicate that simultaneously inhibiting ICOS and CD28 pathways may result in significant disease amelioration in lupus-related inflammation/autoimmunity, with activity superior to agents targeting only one of these pathways. These observations provide further support for the clinical evaluation of acazicolcept for treatment of SLE; a Phase 2 trial of acazicolcept in SLE is ongoing (NCT04835441/Synergy). 1 Ota, M, et al."

IO biomarker • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus • CD80 • CD86 • ICOS • IL17A

ALPN-101 (Acazicolcept) in Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Alpine Immune Sciences, Inc. | Trial completion date: Jan 2024 ➔ Jan 2025 | Trial primary completion date: Nov 2023 ➔ Nov 2024

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

[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

Systemic Administration of Acazicolcept, a Dual CD28 and Inducible T cell Costimulator Inhibitor, Ameliorates Experimental Autoimmune Uveitis. (PubMed, Transl Vis Sci Technol) - "Additional studies are needed to clarify the optimal dose and route for use in humans. We show that T cell costimulatory blockade could be an effective mechanism for treating uveitis."

Journal • Immune Modulation • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Uveitis • CD8 • ICOS • IFNG • IL17A • PTPRC

Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN-101) Reveals Non-Redundant Roles of T Cell Co-Stimulation Pathways in Inflammatory Arthritis. (PubMed, Arthritis Rheumatol) - "Both CD28 and ICOS signaling play critical roles in inflammatory arthritis. Therapeutic agents such as acazicolcept that co-inhibit both ICOS and CD28 signaling may mitigate inflammation and/or disease progression in RA and PsA more effectively than inhibitors of either pathway alone."

IO biomarker • Journal • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CD28 • CTLA4 • ICOS

Systemic Administration of Acazicolcept (ALPN-101), a Dual ICOS/CD28 Antagonist, Suppresses Ocular Inflammation in Rat Experimental Autoimmune Uveitis (ARVO 2022) - "Systemic treatment with acazicolcept significantly suppresses EAU in rats, as evidenced by reduced clinical and histological scores, and correlated with reduced eye-infiltrating IL-17A+ and IFNγ+ T cells. Acazicolcept was well-tolerated without the weight loss induced by steroid treatment. Due to species- and disease-related differences, the dose regimen used in this study is not predictive of the effective dose in humans."

Preclinical • Ocular Inflammation • Ophthalmology • Uveitis • CXCL5 • ICOS • IFNG • IL17A • IL1B • LEP • PTPRC

Acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, demonstrates efficacy in systemic sclerosis preclinical mouse models. (PubMed, Arthritis Res Ther) - "Our results confirm the importance of costimulatory molecules in inflammatory-driven fibrosis. Our data highlight a key role of ICOS and CD28 in SSc. Using complementary models, we demonstrated that dual ICOS/CD28 blockade by acazicolcept decreased dermal and pulmonary fibrosis and alleviated pulmonary hypertension. These results pave the way for subsequent research on ICOS/CD28-targeted therapies."

IO biomarker • Journal • Preclinical • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immune Modulation • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • CD4 • CD69 • ICOS

Alpine Immune Sciences Provides Corporate Update and Reports Second Quarter 2021 Financial Results (Businesswire) - “Acazicolcept: Dual CD28/ICOS inhibitor: Initiated Synergy, an international, double-blind placebo-controlled Phase 2 study of acazicolcept in patients with Systemic Lupus Erythematosus (SLE). Achieved $45 million in pre-option exercise development milestones as part of the 2020 Option and License Agreement with AbbVie, with the potential of an additional $30 million in pre-option exercise development milestones.”

Commercial • Trial status • Immunology • Lupus • Systemic Lupus Erythematosus

A Study of ALPN-101 in Active Lupus Estudio de ALPN-101 en el lupus activo (clinicaltrialsregister.eu) - P2; N=130; Ongoing; Sponsor: Alpine Immune Sciences, Inc.

New P2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CRP

Ministry of Food and Drug Safety approves 7 clinical trials including Yuhan’s urticaria treatment (Health Korea News) - “The Ministry of Food and Drug Safety approved seven clinical trials…As a result, companies that have received approval will soon begin clinical trials to confirm the efficacy and safety of the drug….Parexel Korea…has been approved for a phase 2 clinical trial of Alpine's 'ALPN-101'. This is a trial to find out about 'ALPN-101' in 10 patients with systemic lupus erythematosus. The implementing institutions were known as Kyungpook National University Hospital, Seoul National University Hospital, Ajou University Hospital, and Chonnam National University Hospital.”

New P2 trial • Lupus • Systemic Lupus Erythematosus

ALPN-101 in Systemic Lupus Erythematosus (clinicaltrials.gov) - P2; N=130; Recruiting; Sponsor: Alpine Immune Sciences, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Alpine Immune Sciences Announces First Patient Dosed in Synergy, ALPN-101 Phase 2 Lupus Clinical Trial and $45 million in Development Milestones Achieved Under AbbVie Collaboration (Businesswire) - "Alpine Immune Sciences...announced today that the first patient has been dosed in Synergy, a Phase 2 study of ALPN-101 in patients with Systemic Lupus Erythematosus (SLE). Alpine also announced the achievement of $45 million in pre-option exercise development milestones as part of the 2020 Option and License Agreement with AbbVie."

Commercial • Trial status • Immunology • Lupus

ALPN-101 in Systemic Lupus Erythematosus (clinicaltrials.gov) - P2; N=130; Not yet recruiting; Sponsor: Alpine Immune Sciences, Inc.; Trial completion date: Jun 2023 ➔ Jan 2024; Trial primary completion date: Mar 2023 ➔ Nov 2023

Clinical • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Alpine Immune Sciences Provides Corporate Update and Reports First Quarter 2021 Financial Results (Businesswire) - "General and administrative expenses for the quarter ended March 31, 2021 were $3.3 million...Alpine expects that its current cash resources, combined with the potential $75 million in pre-option exercise milestones payable under its option and license agreement with AbbVie, for the development and commercialization of ALPN-101, are sufficient to fund Alpine's planned operations through 2023."

Commercial • Immunology • Lupus

ALPN-101 in Systemic Lupus Erythematosus (clinicaltrials.gov) - P2; N=130; Not yet recruiting; Sponsor: Alpine Immune Sciences, Inc.

New P2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Alpine Immune Sciences Provides Corporate Update and Reports Fourth Quarter and Full Year 2020 Financial Results (Businesswire) - "ALPN-101: Preparation for a global Phase 2 study in SLE is ongoing with an intent to initiate the study in mid-2021. ALPN-202: Enrollment in NEON-1, a first in human monotherapy Phase 1 clinical trial, continues to progress through its dose escalation cohorts. Alpine plans to share interim data at an appropriate scientific forum and to determine expansion cohorts later this year. Alpine is also targeting the initiation of NEON-2, a Phase 1 combination study of ALPN-202 and a PD-1 inhibitor, later this year...Alpine expects that its current cash resources, combined with the potential $75 million in pre-option exercise milestones payable under its option and license agreement with AbbVie, for the development and commercialization of ALPN-101, are sufficient to fund Alpine's planned operations through 2023."

Commercial • Enrollment status • New P1 trial • New P2 trial • P1 data • Immunology • Lupus • Lymphoma • Oncology • Solid Tumor • Systemic Lupus Erythematosus

First-in-Human Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALPN-101, A Dual CD28/ICOS Antagonist, in Healthy Adult Subjects. (PubMed, Clin Transl Sci) - "In conclusion, ALPN-101 was well-tolerated in healthy subjects with dose-dependent PK and PD consistent with the known biology of the CD28 and ICOS costimulatory pathways. Further clinical development of ALPN-101 in inflammatory and/or autoimmune diseases is therefore warranted."

Clinical • Journal • P1 data • PK/PD data • Immune Modulation • Immunology • Inflammation • ICOS

Alpine Immune Sciences Reports Third Quarter 2020 Financial Results and Provides Corporate Update (Businesswire) - "Alpine and AbbVie have agreed on the design of an international Phase 2 study of ALPN-101 in adults with active lupus, anticipated to commence enrollment in the first half of 2021....Alpine had $141.3 million in cash, cash equivalents, restricted cash, and short-term investments. Alpine expects that its current cash resources, combined with the potential $75 million in pre-option exercise milestones payable under its option and license agreement with AbbVie, for the development and commercialization of ALPN-101, are sufficient to fund Alpine's planned operations into 2024, including a planned Phase 2 study of ALPN-101 in systemic lupus erythematosus..."

Enrollment open • New P2 trial • Immunology • Inflammation • Lupus • Systemic Lupus Erythematosus