SUPLEXA cell therapy / Alloplex Biotherap - LARVOL DELTA

SUPLEXA-101: Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Alloplex Biotherapeutics Inc | N=35 ➔ 46

Enrollment change • First-in-human • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor

Transcriptional and proteomic insights into the immunomodulatory nature of SUPLEXA cells: an autologous cellular therapy for cancers (SITC 2024) - "Longitudinal profiling of plasma cytokine levels identified patients with high inflammatory cytokines that were reduced by SUPLEXA treatments and patients with suppressed plasma cytokines showing specific increases suggesting a homeostatic role for SUPLEXA treatment. Conclusions This approach advances the field of autologous cellular immunotherapy by demonstrating that PBMCs from cancer patients can be trained by an engineered immunomodulatory tumor cell platform to acquire anti-tumor immunity effector activities that appear to translate to the clinical setting for solid tumors."

Immunomodulating • IO biomarker • Oncology • Solid Tumor • CD80 • CD86 • PRF1

Final safety and efficacy update of SUPLEXA-101, a first-in-human, single agent study of SUPLEXA therapeutic cells in metastatic solid tumors (SITC 2024) - P1 | "Conclusions The first-in-human experience demonstrated a pristine safety profile and strong clinical benefit as a single-agent. These early clinical results and mechanistic insights support the design of a Phase 2 SUPLEXA as a highly differentiated approach to cellular therapy as a pan-cancer platform Ethics Approval Ethics Approval Approval was obtained from BellBerry 2021-10-1150 All participants signed PICF before starting the trial."

Clinical • Metastases • P1 data • Microsatellite Instability • Oncology • Solid Tumor • MSI

Transcriptional and proteomic insights into the immunomodulatory nature of SUPLEXA cells: an autologous cellular therapy for cancers (SITC 2024) - "Longitudinal profiling of plasma cytokine levels identified patients with high inflammatory cytokines that were reduced by SUPLEXA treatments and patients with suppressed plasma cytokines showing specific increases suggesting a homeostatic role for SUPLEXA treatment. Conclusions This approach advances the field of autologous cellular immunotherapy by demonstrating that PBMCs from cancer patients can be trained by an engineered immunomodulatory tumor cell platform to acquire anti-tumor immunity effector activities that appear to translate to the clinical setting for solid tumors."

Immunomodulating • IO biomarker • Oncology • Solid Tumor • CD80 • CD86 • PRF1

Final safety and efficacy update of SUPLEXA-101, a first-in-human, single agent study of SUPLEXA therapeutic cells in metastatic solid tumors (SITC 2024) - P1 | "Conclusions The first-in-human experience demonstrated a pristine safety profile and strong clinical benefit as a single-agent. These early clinical results and mechanistic insights support the design of a Phase 2 SUPLEXA as a highly differentiated approach to cellular therapy as a pan-cancer platform Ethics Approval Ethics Approval Approval was obtained from BellBerry 2021-10-1150 All participants signed PICF before starting the trial."

Clinical • Metastases • P1 data • Microsatellite Instability • Oncology • Solid Tumor • MSI

Cancer trial: retraining immune cells offers new hope for patients in personalized medicine breakthrough (PRNewswire) - P1 | N=35 | NCT05237206 | Sponsor: Alloplex Biotherapeutics Inc | "Full results of the first-in-human trial will be released at the 2024 SITC conference in November. The Australian study showed no treatment-related serious adverse eventss...Three CRC patients derived significant clinical benefit: one achieved a complete response (CR), another a partial response (PR) and another stable disease...Of the ten RCC patients, one achieved a partial response (PR) and six achieved stable disease (SD) while only 3 had progressive disease (PD). Patients with other solid tumors, including melanoma, breast and lung cancer, also demonstrated long-term SD with SUPLEXA...With encouragement from the FDA to proceed with an Investigational New Drug (IND) submission, Alloplex Biotherapeutics plans to initiate Phase 2 clinical trials of SUPLEXA in early 2025."

IND • P1 data • Breast Cancer • Colorectal Cancer • Lung Cancer • Melanoma • Renal Cell Carcinoma

SUPLEXA-101: Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Alloplex Biotherapeutics Inc | Active, not recruiting ➔ Completed | N=60 ➔ 35 | Trial completion date: Feb 2025 ➔ Jul 2024 | Trial primary completion date: Feb 2024 ➔ Jul 2024

Enrollment change • Metastases • Trial completion • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor

Effect of novel autologous immune training platform on end-stage patients with cancer. (ASCO 2024) - P1 | "SUPLEXA therapeutic cells are a highly differentiated approach to cellular therapy. The first-in-human experience demonstrated a pristine safety profile and strong clinical benefit as a single-agent. The pharmacodynamic decrease of in the number of MDSCs, known to suppress the anti-tumor immune response and limit immune checkpoint inhibitors (ICIs) efficacy, supports the further clinical testing to test the hypothesis that the multiple mechanisms of SUPLEXA cells will enhance the clinical activity of ICIs."

Clinical • Oncology • Solid Tumor • CD14

Topline safety and efficacy update of SUPLEXA-101, a first-in-human, single agent study of SUPLEXA therapeutic cells in 28 patients with metastatic solid tumours (SITC 2023) - P1 | "Greater than 70% of the patients showed early signals of SD or PR by RECIST criteria. This FIH trial is now closed to enrolment with plans the next SUPLEXA clinical trial underway now that safety and encouraging efficacy clinical outcomes have been established."

Clinical • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8

SUPLEXA, a multimodal autologous cellular therapy, shows immunomodulatory behavior in cancer patients consistent with improved anti-tumor immune function (SITC 2023) - "Conclusions SUPLEXA therapeutic cells from patients’ PBMCs develop potent tumor cytolytic phenotypes. Longitudinal changes in circulating immune cell types and cytokine levels in SUPLEXA treated cancer patients indicate improved anti-tumor immune function and homeostasis."

Clinical • Immunomodulating • IO biomarker • Oncology • Solid Tumor • B3GAT1 • CD14 • CD70 • CD8 • CXCL8 • IFNG • IL6 • KLRG1 • NKG2D • PRF1 • SIGLEC5 • TIGIT

SUPLEXA Platform for Reprogramming of Immune Cells for Treatment of Cancer (IO-SUMMIT EUROPE 2023) - "SUPLEXA therapeutic cells represent a novel approach to adoptive cellular therapy involving the activation, differentiation, and expansion of peripheral blood mononuclear cells to broadly target cancer while sparing normal tissues. Ongoing Phase 1 clinical trial safety and efficacy update Summary of exploratory longitudinal PBMC and plasma analyses from treated patients suggests a potential approach to pharmacodynamic monitoring of SUPLEXA cell activity The absence of drug-related adverse events facilitates future single-agent dose optimization efforts and plans for combination studies."

Immune cell • Oncology

SUPLEXA-101: Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Alloplex Biotherapeutics Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

SUPLEXA-101: Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Alloplex Biotherapeutics Inc | N=40 ➔ 60 | Trial completion date: May 2024 ➔ Feb 2025 | Trial primary completion date: Sep 2023 ➔ Feb 2024

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Clinical update from a Phase 1, First-in-Human, Open-label Single Agent Study of SUPLEXA Therapeutic Cells in Patients with Metastatic Solid Tumours and Haematologic Malignancies (SITC 2022) - P1 | "Conclusions Trial is proceeding well with an excellent tolerability profile and ease of administration for the patients. Additional safety and efficacy data will be forthcoming."

Clinical • P1 data • Chronic Lymphocytic Leukemia • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Pancreatic Cancer • Solid Tumor • CD4

SUPLEXA-101: Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Alloplex Biotherapeutics Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Interleukin-10 and transforming growth factor-beta do not suppress tumor killing activity of PBMC-derived SUPLEXA cells (AACR 2022) - "An in vitro approach was used as a surrogate for what might occur in patients with solid tumors to test whether potent immune suppressive cytokines that are present in the tumor microenvironment might inhibit SUPLEXA cell function. Our findings indicate that IL-10 and TGF-β do not significantly reduce the tumor killing activity of SUPLEXA cells. Instead, we discovered that IL-10 significantly enhances SUPLEXA cell function and cytokine production, which suggests that SUPLEXA cells may acquire heightened tumoricidal activity and promote immune surveillance by augmenting cytokine and chemokine levels within the tumor microenvironment when given therapeutically to cancer patients."

Melanoma • Oncology • Solid Tumor • CD8 • CXCL8 • IFNG • IL10 • TGFB1

Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Alloplex Biotherapeutics Inc

New P1 trial • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Potent Tumor Organoid Infiltration and Killing by PBMC-Derived Effector Cells (SITC 2021) - "SUPLEXA cells will be delivered back to cancer patients via intravenous administrations on a weekly schedule as an autologous adoptive cellular immunotherapy for cancer...The observed activity in both colorectal and lung cancer organoid models support broad anti-tumor killing activity by SUPLEXA. These results provide further evidence that PBMCs from cancer patients can be activated and expanded by our approach as a novel autologous cellular immunotherapy for cancer."

Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8

[VIRTUAL] Engineered immunostimulatory cells can convert PBMCs from chronic lymphocytic leukemia (CLL) patients into potent tumor killing immune cells. (ASCO 2021) - "We demonstrate for the first time that PBMCs from CLL patients can be converted into SUPLEXA cells despite low numbers of normal immune cells at baseline and the known immunologic impairment present in CLL patients . Importantly, SUPLEXA cells derived from CLL patients acquire potent tumor killing activity that is indistinguishable from SUPLEXA cells prepared from NHVs . Taken together, these findings support the feasibility of converting PBMCs from CLL patients with low percentages of NK and T cells into an autologous cellular therapy for cancer."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Leukemia • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IL15 • IL7