INV401 / Apeiron Biologics, MaxCyte - LARVOL DELTA

PALINDROM: PBMC-based Leukocyte Immunotherapy (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: invIOs GmbH | Recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Oct 2024 | Trial primary completion date: Mar 2024 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

PALINDROM: PBMC-based Leukocyte Immunotherapy (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: invIOs GmbH

New P1 trial • Oncology • Solid Tumor

invIOs starts further clinical trial of APN401, novel cell therapy against solid cancers, and secures major Austrian grant funding (GlobeNewswire) - "invIOs GmbH...announces that it has started patient recruitment for a Phase 1b trial of its novel autologous cell therapy, APN401, in patients with solid tumors, and has successfully secured grant funding. The PALINDROM study aims to determine the optimal dosage of APN401 in a multi-site setting for a subsequent Phase 2 study....As part of the Austrian Life Sciences Programme 2023 initiative, the Austrian Research Promotion Agency (FFG) has awarded invIOs funding to support the PALINDROM study....By establishing the maximum tolerated dose (MTD) and/or maximum manufacturable dose (MMD) of APN401, PALINDROM is expected to pave the way for a larger Phase 2 study of APN401, including in earlier lines of treatment and potentially as a combination therapy."

Financing • Trial status • Oncology • Solid Tumor

35 Review on endothelial cell loss of corneal transplants and possible correlations. (PubMed, BMJ Open Ophthalmol) - "The Tissue Bank of the Upper Austrian Red Cross in Linz, Austria, is a multi-tissue bank, processing corneal transplants (for PKP, for DMEK, pre-cut DMEK), homografts (aortic valve, pulmonary valve, pulmonal patch), amnion grafts (frozen or cryopreserved), autologous tissues and cells (ovarian tissue, cranial bone, PBSC) as well as investigational medicinal products and ATMPs (Aposec, APN401).This presentation sums up retrospective data of the endothelial cell count of corneae at the time of first evaluation and at the time of reevaluation before transplantation as well as the cell count of pre-cut DMEK before transplantation.Regarding corneal grafts it is advisable to review the data of the previous years to find potential factors influencing the cell count of corneal tissue...The same seems to be the case regarding duration of cultivation until reevaluation.The aim of the data review was to determine the cell loss of corneal transplants and attempt to identify possible..."

Journal • Review • Ophthalmology • Transplantation

Case report: APN401, a novel cancer therapy using Cbl-b silenced autologous PBMCs, induced stable disease in two patients with advanced solid tumors (AACR 2023) - "Taken together, these initial results indicate that APN401, a novel personalized cancer cell therapy based on targeted silencing of Cbl-b in PBMCs, may be a safe and effective immunotherapy for solid tumors. This cell therapy will be further evaluated as a monotherapy along with potential combinations in clinical trials in various solid tumors.Ethics approval: The clinical trial was approved by the Medical University of Vienna institution’s independent Ethics Committee, approval number 1778/2020."

Clinical • IO biomarker • Late-breaking abstract • Metastases • Appendix Cancer • Head and Neck Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • IFNG • IL2 • UBR5

invIOs presents promising new clinical data in solid tumors from autologous cell therapy APN401 at AACR Annual Meeting 2023 (GlobeNewswire) - P=NA, N=2 | "APN401 induced prolonged stable disease in two heavily pre-treated patients, using invIOs’s proprietary rapid cell-processing platform technology to manufacture Cbl-b silenced PBMCs and deliver treatment in under 24 hours....Data underscores potential of invIOs’s pioneering approach targeting the master immune checkpoint Cbl-b."

Clinical data • Oncology • Solid Tumor

Enhancement Platform for immune Cells (EPiC): invIOs's innovative cell-therapy platform for creating personalized cancer treatments (ESMO-TAT 2023) - "APN401 is an autologous cell therapy comprising peripheral blood mononuclear cells (PBMCs), while INV441 utilizes tumor infiltrating lymphocytes (TILs). The advantage of using an RNAi-based technology is that it allows transient and highly specific modification of immune cells. Beyond silencing, EPiC enables over-expression of proteins and combinations of modalities (e.g. mRNA) to modify multiple immune pathways and create the next generation of personalized immune cell therapies."

Immune cell • IO biomarker • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • UBR5

Adoptive cellular immunotherapy with APN401, autologous cbl-b silenced peripheral blood mononuclear cells: Data from a phase I study in patients with solid tumors. (ASCO 2018) - P1; "Cbl-b-silenced PBMCs (APN401) from cancer patients respond to TCR stimulation and activation with tumor antigens. Strongest cell activation was seen in the patient with the best objective clinical response. 50 x 105 / kg APN401 was safe and well tolerated."

Clinical • P1 data • Colorectal Cancer • Lymphoma • Renal Cell Carcinoma

Cbl-b silenced, autologous PBMCs as a novel anti-cancer therapy using the closed cell processing platform EPiC - a phase 1b trial with APN401 (SITC 2022) - P1 | "Dose escalation is ongoing, and patients are being enrolled in the second dosing cohort (1.5 x10 7 PBMCs/kg). Ethics Approval The study is approved by Medical University of Vienna institution’s independent Ethics Board, approval number 1778/2020."

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

APN401, a novel EPiC-based anti-cancer cell therapy, case report: Cbl-b silenced, autologous PBMCs induced stable disease in an appendix carcinoma patient (SITC 2022) - "Conclusions Our findings highlight that APN401,an autologous cell therapy based on selective Cbl-b silencing, may be a safe, potent, and effective immunotherapy for solid tumors. Ethics Approval The study is approved by Medical University of Vienna institution’s independent Ethics Board, approval number 1778/2020."

Clinical • IO biomarker • Appendix Cancer • Hematological Malignancies • Lymphoma • Oncology • CD4 • CD8 • IFNG • IL2

invIOs presents positive patient data from ongoing Phase 1b trial of APN401 cell therapy in advanced solid tumors at SITC 2022 (GlobeNewswire) - P1 | N=NA | "The poster, 'APN401, a novel EpiC-based anti-cancer cell therapy, case report: Cbl-b silenced, autologous PBMCs induced stable disease in an appendix carcinoma patient', presents the case of a patient who was initially diagnosed with appendix carcinoma that had metastasized into the peritoneum and liver....Treatment with APN401 was well tolerated and the patient presented with stable disease for 27 weeks, suggesting immunological anti-tumor activity resulting from treatment with APN401."

P1 data • Appendix Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Peritoneal Cancer • Solid Tumor

invIOs presents positive patient data from ongoing Phase 1b trial of APN401 cell therapy in advanced solid tumors at SITC 2022 (GlobeNewswire) - "The design of the Phase 1b clinical trial is also being presented at the SITC meeting in a second poster entitled 'Cbl-b silenced, autologous peripheral blood mononuclear cells as a novel anti-cancer therapy using the closed cell processing platform EpiC – a phase 1b trial with APN401'. The trial is an open-label, multi-center, dose escalation and expansion study with two parts. In Part A, three ascending dose levels are being evaluated with three patients each (3+3 design) to determine the maximum tolerated dose (MTD) in patients with a variety of solid tumors."

Clinical protocol • Oncology • Solid Tumor

invIOs to present data from clinical stage Cbl-b program at SITC 2022 (GlobeNewswire) - "invIOs GmbH...announces that two abstracts on its clinical stage lead program, APN401, have been accepted for poster presentations at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022) being held in Boston, MA, on November 8-12, 2022. The posters will present new data from the ongoing Phase 1b clinical trial of APN401, a candidate treatment from invIOs’s EPiC cell therapy platform targeting the master checkpoint inhibitor Cbl-b."

P1 data • Appendix Cancer • Gastrointestinal Cancer • Oncology

APEIRON shareholders approve new group structure geared towards enabling innovation and growth (GlobeNewswire) - "The approved demerger of APEIRON Biologics AG's 100% shareholding in invIOs GmbH (invIOs) leads to the foundation of invIOs Holding AG, which bundles the operations of its wholly owned subsidiaries, invIOs GmbH and APEIRON Respiratory Therapies GmbH (AResT). Shareholders in APEIRON Biologics AG will be granted shares in invIOs Holding AG pro rata to their current shareholdings in APEIRON Biologics AG....invIOs will continue to focus on developing novel immuno-oncology treatments for difficult-to-treat cancers with its cell therapy platform EPiC (Enhancement Platform for immune Cells) and clinical-stage lead asset, APN401....APEIRON Biologics AG continues to hold the IP and license for its marketed product, Qarziba® (APN311), which is globally licensed to EUSA Pharma Ltd."

M&A • Oncology

APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1; N=11; Completed; Sponsor: Wake Forest University Health Sciences; Active, not recruiting ➔ Completed; Trial completion date: May 2024 ➔ Dec 2020

Clinical • Trial completion • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Immunology • Oncology • Pancreatic Cancer • Solid Tumor

APEIRON Biologics launches next clinical trial with innovative cancer therapy APN401 (Yahoo Finance) - "APEIRON Biologics AG announced today the start of a Phase Ib clinical trial with its product candidate APN401 for the treatment of solid tumors...The open-label, multi-center Phase Ib clinical trial is expected to enroll approximately 60 patients at multiple sites in Austria. The study objective is to evaluate the safety, tolerability and immunological effects of the treatment on patients with various solid tumors...The Phase I clinical study will start at the Medical University of Vienna (MUW) where the GMP-certified production of the cell therapy and treatment of the patients will take place."

New P1 trial • Oncology • Solid Tumor

APEIRON Biologics and MaxCyte Enter into Clinical and Commercial Licensing Agreement for APN401 (PRNewswire) - "APEIRON Biologics...today announces the signing of a clinical and commercial licensing agreement. APEIRON Biologics will obtain non-exclusive clinical and commercial rights to use MaxCyte's Flow Electroporation® technology and ExPERT™ platform for the advancement of APN401, a siRNA-based cell therapy currently in clinical development for various solid tumors."

Licensing / partnership • Oncology • Solid Tumor

APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1; N=10; Recruiting; Sponsor: Wake Forest University Health Sciences; Trial completion date: Apr 2018 ➔ Oct 2018; Trial primary completion date: Apr 2018 ➔ Oct 2018

Trial completion date • Trial primary completion date • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Apeiron to present clinical data on two immunotherapy programs at the 2018 ASCO Annual Meeting (GlobeNewswire) - "APEIRON Biologics AG...announced it would present data on two of its key programs in three poster presentations at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, being held on June 1-5, 2018, in Chicago, IL...These data summarize the results of a Phase I study with APEIRON’s innovative project APN401 [first presentation]...The therapy modifies isolated patients' own blood cells (mononuclear cells of peripheral blood), by ex vivo silencing of the intracellular 'master checkpoint' protein cbl-b....In the second and third presentations, APEIRON is co-author of two abstracts on its monoclonal antibody ch14.18/CHO (Qarziba®) for the immunotherapy of pediatric neuroblastoma."

Clinical data • Oncology

APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1; N=11; Active, not recruiting; Sponsor: Wake Forest University Health Sciences; Trial primary completion date: May 2020 ➔ Jul 2019

Clinical • Trial primary completion date

Checkpoint Cbl-b siRNA-based APN401 adoptive cell therapy: Superior efficacy & immune memory induction in murine hepatocellular carcinoma following APN401 monotherapy and synergism with anti-PD1. (SITC 2019) - "APN401 monotherapy demonstrates striking anti-tumor efficacy in the murine hepatocellular carcinoma Hepa1-6 model. The preclinical synergistic effects of APN401 with anti-PD1 support its therapeutic utility as a combination therapy with immune checkpoint anti-PD1 treatment. The significant TGI observed following tumor rechallenge indicate that prior selective cell-based Cbl-b-silencing with APN401 alone or in combination with anti-PD1 induced systemic and durable anti-tumor immune memory responses."

Monotherapy • Preclinical

APEIRON to present preclinical data at the 2019 AACR-NCI-EORTC Conference (BioSpace) - "Poster: C048 - Novel master checkpoint Cbl-b siRNA-based adoptive cellular therapy: Superior anti-tumor efficacy in a syngeneic murine hepatocellular carcinoma Hepa1-6 model following APN401 monotherapy and synergistic effects with anti-PD1.... Anthony El-Khoueiry..."

Preclinical

Novel master checkpoint Cbl-b siRNA-based adoptive cellular therapy: Superior antitumor efficacy in a syngeneic murine hepatocellular carcinoma Hepa1-6 model following APN401 monotherapy and synergistic effects with anti-PD1 (AACR-NCI-EORTC 2019) - "APN401 monotherapy demonstrates striking anti-tumor efficacy in suppressing tumor growth in a murine hepatocellular carcinoma Hepa1-6 model. The preclinical synergistic effects of APN401 with anti-PD1 support its therapeutic utility as a combination therapy with immune checkpoint anti-PD1 treatment. These findings highlight the potential promise of selective Cbl-b silencing by APN401 as a novel immunotherapy for cancer."

Monotherapy • Preclinical

Master checkpoint Cbl-b inhibition: Anti-tumour efficacy in a murine colorectal cancer model following siRNA-based cell therapy (ESMO 2019) - "Further discovery efforts led to the advancement of APN401, an ex vivo human Cbl-b siRNA-based autologous cellular therapy, currently in clinical development in patients with advanced solid tumors... In a model of murine colon cancer, Cbl-b-silencing induced vigorous in vivo anti-tumorigenic immune responses. The treatment modality was safe and well tolerated. These data provide direct preclinical proof of concept that siRNA-based silencing of Cbl-b provides a novel, effective and tunable approach as cellular immunotherapy."

Preclinical

APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery (clinicaltrials.gov) - P1; N=11; Active, not recruiting; Sponsor: Wake Forest University Health Sciences; Suspended ➔ Active, not recruiting; Trial completion date: Oct 2019 ➔ May 2024; Trial primary completion date: Oct 2019 ➔ May 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date