KD-025 CAR T-cells / KAEDI - LARVOL DELTA

Thermosensitive hyaluronic acid-manganese-capsaicin complex nanogel improving NKG2D/CAR-T melanoma treatment through adjusting tumor microenvironment. (PubMed, Int J Biol Macromol) - "The results of immunohistochemistry and immunofluorescence assays showed that the combined HA-Mn-CAP Gel and NKG2D/CAR-T significantly increased the proliferation and infiltration of T cells, especially for CD8+ cells. Therefore, the new promising strategy of increasing the target ligand expression and adjusting TME before administering CAR-T cells is suitable for treating solid tumors."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Melanoma • Oncology • Solid Tumor • CD8 • NKG2D • ULBP2

NKG2D CAR-T(KD-025) in the Treatment of Advanced NKG2DL+ Solid Tumors (clinicaltrials.gov) - P=N/A | N=9 | Recruiting | Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Metastases • New trial • Oncology • Solid Tumor

Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer. (PubMed, Cancer Sci) - "In sum, our study reveals the role of DKK1 in remodeling GC TIME and regulating the expression levels of NKG2DLs in GC. We also provide a promising treatment strategy of combining DKK1 inhibition with NKG2D-CAR-T cell therapy, which could bring new breakthroughs for GC immunotherapy."

CAR T-Cell Therapy • Combination therapy • IO biomarker • Journal • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • DKK1 • NKG2D

Interim Analysis of KD025-213: A Phase 2, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of KD025 in Subjects with Chronic Graft Versus Host Disease (cGVHD) after at Least 2 Prior Lines of Systemic Therapy (The ROCKstar Study; NCT03640481) (TCT-ASTCT-CIBMTR 2020) - P2, P2a; "Introduction: KD025 is an orally available Rho-associated coiled-coil kinase 2 (ROCK2) selective inhibitor that decreases pro-inflammatory Stat3 and increases Stat5 favoring regulatory T cells... We randomly assigned cGVHD patients (pts) after 2-5 prior LOT to KD025 200mg QD (n=66), or KD025 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib... Clinically meaningful ORR has been achieved in this population of cGVHD pts with QD and BID dosing, consistent with previous observations. ORR was consistent across key subgroups. KD025 has been generally well tolerated."

Clinical • Late-breaking abstract • P2 data • STAT5

KD025 for Patients with Chronic Graft-Versus-Host Disease (cGVHD) – Long-Term Follow-up of a Phase 2a Study (KD025-208) (TCT-ASTCT-CIBMTR 2020) - "KD025 is an orally available Rho-associated coiled-coil kinase 2 (ROCK2) selective inhibitor...Baseline median CS dose was 0.21 mg/kg/day (prednisone eq)... Durable and clinically meaningful responses have been seen across all 3 cohorts. KD025 was well tolerated, with sustained responses and encouraging FFS in patients with advanced cGVHD."

Clinical • P2a data

[VIRTUAL] Belumosudil for Chronic Graft-Versus-Host Disease (cGVHD) after 2 or More Prior Lines of Therapy: The Rockstar Study (KD025-213) (ASH 2020) - "Introduction: Belumosudil (KD025) is a novel oral selective rho-associated coiled-coil kinase 2 (ROCK2) inhibitor specifically designed for the treatment of cGVHD, an immune-mediated inflammatory and fibrotic disorder. Treatment with belumosudil at both doses resulted in high ORRs across key subgroups, meeting the primary end point of this pivotal randomized trial in cGVHD. Responses were durable and clinically meaningful, irrespective of patient and cGVHD characteristics, and were seen in patients who previously received ruxolitinib and ibrutinib. Belumosudil was well tolerated, with limited and manageable AEs."

Cytomegalovirus Infection • Fatigue • Fibrosis • Graft versus Host Disease • Immunology • Infectious Disease • Pain • Respiratory Diseases

Tandem CAR-T cells targeting CLDN18.2 and NKG2DL for treatment of gastric cancer. (ASCO 2022) - "Our work construct a tandem CAR molecule targeting two tumor-associated antigens, NKG2DL and CLDN18.2, and found that Tan-CAR-T cells（KD-496）distinctly recognize the antigens and exhibited superior antitumor effect. KD-496 CAR-T cells potently respond to GC and more efficient tumor elimination than single CAR such as KD-025 and KD-182 CAR-T cells in PDX model with no obvious safety issue. The results support future clinical trial of KD-496 CAR in patients with GC, where the need for effective treatment is great."

CAR T-Cell Therapy • IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • CD8 • CLDN18 • CLDN8 • IFNG • NKG2D

NKG2D CAR-T(KD-025) in the Treatment of Advanced NKG2DL+ Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: jianming xu

New P1 trial • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor

NKG2D-based CAR T-cells Immunotherapy for Patient With r/r NKG2DL+ Solid Tumors (clinicaltrials.gov) - P1; N=3; Recruiting; Sponsor: Fudan University

CAR T-Cell Therapy • Clinical • New P1 trial • Brain Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Hepatocellular Cancer • Medulloblastoma • Oncology • Solid Tumor • NKG2D

[VIRTUAL] BELUMOSUDIL FOR CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) AFTER 2 OR MORE PRIOR LINES OF THERAPY: THE ROCKSTAR STUDY (KD025-213) (EBMT 2021) - P2 | " We randomly assigned cGVHD patients (pts) after 2-5 prior lines of therapy (LOT) to belumosudil 200mg QD (n=66), or belumosudil 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib use. Treatment with belumosudil at both doses resulted in high ORRs across key subgroups, meeting the primary end point of this pivotal randomized trial in cGVHD. Responses were durable and clinically meaningful, irrespective of patient and cGVHD characteristics and organ involvement. Belumosudil was well tolerated, allowing pts to remain on treatment and realize potential benefits of sustained therapy."

Cytomegalovirus Infection • Epstein-Barr Virus Infections • Fibrosis • Graft versus Host Disease • Immunology

[VIRTUAL] BELUMOSUDIL FOR CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) AFTER 2 OR MORE PRIOR LINES OF THERAPY: THE ROCKSTAR STUDY (KD025-213) (EBMT 2021) - P2 | " We randomly assigned cGVHD patients (pts) after 2-5 prior lines of therapy (LOT) to belumosudil 200mg QD (n=66), or belumosudil 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib use. Treatment with belumosudil at both doses resulted in high ORRs across key subgroups, meeting the primary end point of this pivotal randomized trial in cGVHD. Responses were durable and clinically meaningful, irrespective of patient and cGVHD characteristics and organ involvement. Belumosudil was well tolerated, allowing pts to remain on treatment and realize potential benefits of sustained therapy."

Cytomegalovirus Infection • Epstein-Barr Virus Infections • Fibrosis • Graft versus Host Disease • Immunology

[VIRTUAL] BELUMOSUDIL FOR CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) AFTER 2 OR MORE PRIOR LINES OF THERAPY: THE ROCKSTAR STUDY (KD025-213) (EBMT 2021) - P2 | " We randomly assigned cGVHD patients (pts) after 2-5 prior lines of therapy (LOT) to belumosudil 200mg QD (n=66), or belumosudil 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib use. Treatment with belumosudil at both doses resulted in high ORRs across key subgroups, meeting the primary end point of this pivotal randomized trial in cGVHD. Responses were durable and clinically meaningful, irrespective of patient and cGVHD characteristics and organ involvement. Belumosudil was well tolerated, allowing pts to remain on treatment and realize potential benefits of sustained therapy."

Cytomegalovirus Infection • Epstein-Barr Virus Infections • Fibrosis • Graft versus Host Disease • Immunology

[VIRTUAL] BELUMOSUDIL FOR CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) AFTER 2 OR MORE PRIOR LINES OF THERAPY: THE ROCKSTAR STUDY (KD025-213) (EBMT 2021) - P2 | " We randomly assigned cGVHD patients (pts) after 2-5 prior lines of therapy (LOT) to belumosudil 200mg QD (n=66), or belumosudil 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib use. Treatment with belumosudil at both doses resulted in high ORRs across key subgroups, meeting the primary end point of this pivotal randomized trial in cGVHD. Responses were durable and clinically meaningful, irrespective of patient and cGVHD characteristics and organ involvement. Belumosudil was well tolerated, allowing pts to remain on treatment and realize potential benefits of sustained therapy."

Cytomegalovirus Infection • Epstein-Barr Virus Infections • Fibrosis • Graft versus Host Disease • Immunology

[VIRTUAL] Belumosudil for Chronic Graft-Versus-Host Disease (cGVHD) after 2 or More Prior Lines of Therapy: The Rockstar Study (KD025-213) (TCT-ASTCT-CIBMTR 2021) - "Introduction: Belumosudil (KD025) is a novel oral selective rho-associated coiled-coil kinase 2 (ROCK2) inhibitor specifically designed for the treatment of cGVHD, an immune-mediated inflammatory and fibrotic disorder. Treatment with belumosudil at both doses resulted in high ORRs across key subgroups, meeting the primary end point of this pivotal randomized trial in cGVHD. Responses were durable and clinically meaningful, irrespective of patient and cGVHD characteristics, and were seen in patients who previously received ruxolitinib and ibrutinib. Belumosudil was well tolerated with manageable AEs."

Cytomegalovirus Infection • Fatigue • Fibrosis • Graft versus Host Disease • Immunology • Infectious Disease • Pain • Respiratory Diseases

[VIRTUAL] Phase 1 Study of Axatilimab (SNDX-6352), a CSF-1R Humanized Antibody, for Chronic Graft-Versus-Host Disease after 2 or More Lines of Systemic Treatment (ASH 2020) - "Prior therapies received by the responders included ibrutinib (6 pts), ruxolitinib (5 pts), and KD025 (3 pts); 3 of the responding pts had received all of these. These data demonstrate that axatilimab is clinically active with acceptable safety profile and responses observed in heavily pretreated pts with active cGVHD. Enrollment continues in the Phase 1 study at 3 mg/kg q4w and Phase 2 study at a dose of 1 mg/kg q2w."

P1 data • Graft versus Host Disease • Hepatology • Immunology • Myositis • Oncology • Pancreatitis • Solid Tumor • Transplantation • CD14 • CSF1R

Portonbio announced strategic cooperation with KAEDI to accelerate the R&D and production of CAR-T drugs (PRNewswire) - "Porton Biologics Ltd. (hereinafter referred to as Portonbio) announced a strategic cooperation with Nanjing KAEDI Biotech, Inc. (hereinafter referred to as KAEDI). Portonbio will offer CMC services for KAEDI's CAR-T cell therapies with its end-to-end CDMO platform for gene and cell therapies to help accelerate their development process. According to the agreement, Portonbio, as an exclusive CDMO partner, will provide KAEDI with CMC services for multiple CAR-T projects, including the process development and manufacturing of plasmids, viral vectors and CAR-T cells and IND filling (CMC part) support services."

Licensing / partnership • CNS Tumor • Glioblastoma • Glioma • Liver Cancer • Oncology

Porton spurs CAR-T development with Kaedi (GBI Health) - "China-based Contract Development and Manufacturing Organization (CDMO) Suzhou Porton Biologics Ltd struck a partnership with compatriot firm Kaedi Biotechnology Co., Ltd (GBI translation), a cell therapy specialist based in Nanjing. As per the agreement, Porton will provide Chemical Manufacturing and Control (CMC) services in relation to multiple CAR-T programs as Kaedi's sole CDMO, including process development and production of plasmids, viral vectors, and CAR-T cells, while also supporting an investigational new drug (IND) filing for the CMC service. The first cooperation program is KD-025, a CAR-T therapy under development to treat liver cancer and glioma."

Licensing / partnership • CNS Tumor • Gastrointestinal Cancer • Glioma • Hepatocellular Cancer • Oncology

[VIRTUAL] KD025 FOR PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) - LONG-TERM FOLLOW-UP OF A PHASE 2A STUDY (KD025-208) (EBMT 2020) - P2a | "Baseline median CS dose was 0.2 mg/kg/day (prednisone eq)... Durable and clinically meaningful responses have been seen across all 3 cohorts. KD025 was well tolerated, allowing pts to remain on treatment and realize benefits of sustained therapy. Clinical Trial Registry: NCT02841995 http://clinicaltrials.gov/ct@/show/NCT02841995"

Clinical • P2a data • Cardiovascular • Fatigue • Fibrosis • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • Pain • Pneumonia • Respiratory Diseases • Thrombocytopenia

[VIRTUAL] KD025 FOR PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) - LONG-TERM FOLLOW-UP OF A PHASE 2A STUDY (KD025-208) (EBMT 2020) - P2a | "Baseline median CS dose was 0.2 mg/kg/day (prednisone eq)... Durable and clinically meaningful responses have been seen across all 3 cohorts. KD025 was well tolerated, allowing pts to remain on treatment and realize benefits of sustained therapy. Clinical Trial Registry: NCT02841995 http://clinicaltrials.gov/ct@/show/NCT02841995"

Clinical • P2a data • Cardiovascular • Fatigue • Fibrosis • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • Pain • Pneumonia • Respiratory Diseases • Thrombocytopenia

[VIRTUAL] KD025 FOR PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD) - LONG-TERM FOLLOW-UP OF A PHASE 2A STUDY (KD025-208) (EBMT 2020) - P2a | "Baseline median CS dose was 0.2 mg/kg/day (prednisone eq)... Durable and clinically meaningful responses have been seen across all 3 cohorts. KD025 was well tolerated, allowing pts to remain on treatment and realize benefits of sustained therapy. Clinical Trial Registry: NCT02841995 http://clinicaltrials.gov/ct@/show/NCT02841995"

Clinical • P2a data • Cardiovascular • Fatigue • Fibrosis • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • Pain • Pneumonia • Respiratory Diseases • Thrombocytopenia

[VIRTUAL] INTERIM ANALYSIS OF KD025-213: A PHASE 2, RANDOMIZED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF KD025 IN SUBJECTS WITH CGVHD (THE ROCKSTAR STUDY) (EBMT 2020) - P2, P2a | " We randomly assigned cGVHD patients (pts) after 2-5 prior LOT to KD025 200mg QD (n=66), or KD025 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib... Clinically meaningful ORR has been achieved in this population of cGVHD pts with QD and BID dosing, consistent with previous observations. ORR was consistent across key subgroups. KD025 has been generally well tolerated."

Clinical • P2 data • Cardiovascular • Fatigue • Graft versus Host Disease • Infectious Disease • Pneumonia • Respiratory Diseases • STAT3 • STAT5

[VIRTUAL] INTERIM ANALYSIS OF KD025-213: A PHASE 2, RANDOMIZED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF KD025 IN SUBJECTS WITH CGVHD (THE ROCKSTAR STUDY) (EBMT 2020) - P2, P2a | " We randomly assigned cGVHD patients (pts) after 2-5 prior LOT to KD025 200mg QD (n=66), or KD025 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib... Clinically meaningful ORR has been achieved in this population of cGVHD pts with QD and BID dosing, consistent with previous observations. ORR was consistent across key subgroups. KD025 has been generally well tolerated."

Clinical • P2 data • Cardiovascular • Fatigue • Graft versus Host Disease • Infectious Disease • Pneumonia • Respiratory Diseases • STAT3 • STAT5

[VIRTUAL] INTERIM ANALYSIS OF KD025-213: A PHASE 2, RANDOMIZED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF KD025 IN SUBJECTS WITH CGVHD (THE ROCKSTAR STUDY) (EBMT 2020) - P2, P2a | " We randomly assigned cGVHD patients (pts) after 2-5 prior LOT to KD025 200mg QD (n=66), or KD025 200mg BID (n=66), across 28 sites, stratified according to cGVHD severity and prior ibrutinib... Clinically meaningful ORR has been achieved in this population of cGVHD pts with QD and BID dosing, consistent with previous observations. ORR was consistent across key subgroups. KD025 has been generally well tolerated."

Clinical • P2 data • Cardiovascular • Fatigue • Graft versus Host Disease • Infectious Disease • Pneumonia • Respiratory Diseases • STAT3 • STAT5

"KD025: Truly a #ROCKstar in pts w SR-cGVH: ORR 75% w ~90% ORR & ~30% CR in joint/fascia/GI. 12m FFS 50%; median DOR of~1 yr ~20% able to d/c steroids and CNI. Overall tolerable w mostly low grade GI s/e (~30%) DOC for scleroderma after ibrutinib failure? #TCTM21 @gvhd_hub" (@hamzahashmi87)

Clinical • Fibrosis • Graft versus Host Disease • Immunology • Scleroderma • Systemic Sclerosis

"Axatilimab randomized study upcoming. Look for AGAVE-201, will be open to patients age 6+. In phase I, responses observed after prior ibrutinib, ruxolitinib, and KD025:" (@sghmd)

Clinical