invIOs presents positive patient data from ongoing Phase 1b trial of APN401 cell therapy in advanced solid tumors at SITC 2022

- Poster presentation shows treatment with APN401, an autologous cell therapy product targeting the master immune checkpoint Cbl-b, resulted in stabilization of disease for more than six months in a heavily pre-treated patient with metastatic appendix carcinoma

- APN401 is manufactured from a patient’s fresh immune cells using EPiC, invIOs’s proprietary closed cell‑processing platform, with a needle-to-needle time of approximately 24 hours

- Second invIOs poster at SITC 2022 presents design of ongoing multi-center Phase 1b dose escalation and expansion trial of APN401, as well as EPiC

invIOs GmbH (“invIOs”), a privately held biotechnology company developing novel therapies for cancer, today presented data from the ongoing clinical trial of its APN401 cell therapy at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022) in Boston, MA. The patient case report shows that a heavily pre-treated patient with metastatic appendix carcinoma achieved stable disease over the course of 27 weeks of treatment with invIOs’s Cbl‑b silenced cell therapy.

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.

Following tumor resection and 11 lines of prior systemic therapy, the patient was enrolled in the ongoing Phase 1b trial presenting with progressive disease. Multiple infusions of APN401 were administered through intravenous delivery route every three weeks respectively followed by safety evaluation. Within a timeframe of 44 weeks, the patient received six cycles of APN401 at dose level 1 (5 x 106 PBMCs/kg) followed by six cycles of APN401 at dose level 2 (1.5 x 107 PBMCs/kg). 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.

Analysis of the patient’s Cbl-b-silenced PBMCs (peripheral blood mononuclear cells) showed increased cytotoxicity, indicated by an elevated CD8+/CD4+ ratio, and increased potency, as evidenced by elevated IL-2 levels. Further, biomarker analysis of the patient’s T cells before each infusion cycle revealed an accumulation of three T cell clonotypes during the treatment period, as well as improved immunity and anti-tumor reactivity, as determined via a surrogate marker. This supports the potency of APN401 and its potential as an effective therapeutic for malignancies, which is being further investigated in the ongoing clinical trial.

“We are pleased to report the case of this patient who responded to treatment with APN401. After a staggering 11 previous different treatments, this patient’s advancing cancer turned into stable disease for six months under APN401 treatment. In addition to first signs of clinical activity, APN401 has been shown to be a safe and well tolerated therapy for the patients we have treated so far in this and earlier trials. I look forward to continuing to enroll patients in this important trial and to seeing the progress of this novel therapy as it advances in development,” said Professor Nina Worel of the Department of Blood Group Serology and Transfusion Medicine at the Medical University of Vienna, coordinating and principal investigator of the trial and co-author of the abstract being presented at SITC.

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. In Part B, the MTD will be used to treat 15 patients with various solid tumors. The primary objective of the trial is to determine the recommended dose for APN401 for future trials as well as to evaluate safety and tolerability. Preliminary signs of efficacy will also be assessed.

Dr Romana Gugenberger, CMSO of invIOs, said: “We believe our new cell therapy approach could be a game-changer for the treatment of solid tumors, similar to how CAR-Ts have been for the treatment of some hematological cancers. This encouraging case report from our ongoing study with APN401 provides important support for invIOs’s approach of silencing the master checkpoint Cbl-b in immune cells to enable powerful anti-tumor immune responses. The progress of the trial so far demonstrates that decentralized cell processing for APN401 is feasible with our EPiC cell-processing platform within only a few hours. We look forward to further advancing this novel cell therapy in the clinic.”

 Details of the invIOs SITC 2022 poster presentations

The posters are on display in the Poster Hall located in Hall C of the Boston Convention & Exhibition Center on Thursday, November 10, 2022 (9 a.m. to 9 p.m) and on Friday, November 11, 2022 (9 a.m. to 8:30 p.m).

The ePosters can also be viewed in the SITC 2022’s Virtual ePoster Hall, the SITC meeting app, and the SITC virtual meeting platform.

The corresponding abstracts have been published in a supplement of the Journal for ImmunoTherapy of Cancer.

 About APN401

ANP401 is a first-in-class out‑patient approach to strengthen immune reactivity by temporarily reducing expression of the master immune checkpoint inhibitor Cbl-b in autologous PBMCs using siRNA. It is the first candidate treatment from EPiC (Enhancement Platform for Immune Cells), invIOs’s proprietary closed cell therapy platform for intracellular modification of gene expression. With EPiC, Cbl-b silenced, autologous PBMCs can be manufactured and reinfused to the patient in approximately 24 hours, which is a significant advantage over currently available cell therapies that require up to several weeks of processing time.

Cbl-b is regarded as a master checkpoint of the immune system that itself controls multiple relevant immune checkpoints simultaneously. It has been shown that Cbl-b deficiency overrides signaling from both CTLA-4 and PD-L1/PD-1 checkpoints and thus makes cells resistant to the inhibitory signals used by many solid tumors for immune evasion. invIOs’s approach based on Cbl-b siRNA aims to supercharge immune cells to fight tumors by inhibiting Cbl-b production.

 About invIOs

invIOs is a privately held biotech company based in Vienna, Austria, focusing on the discovery and development of innovative cancer immunotherapies.

EPiC, invIOs’s proprietary cell therapy platform for intracellularly modifying gene expression, enables rapid treatment of patients in an out-patient setting using their own fresh immune cells. Once clinically validated, this novel concept will allow access to and treatment for indications not previously addressable by immunotherapy. The first EPiC-based candidate, APN401, is already being evaluated in human patients.

APN401 is the first candidate treatment that leverages the EPiC platform. It is a first-in-class out-patient approach to strengthen immune reactivity by targeting the intracellular master immune checkpoint inhibitor Cbl-b. APN401 is currently being evaluated in a Phase 1b clinical trial in patients with advanced solid tumors.

INV441, the second candidate from the EPiC platform, is a tumor-specific cell therapy that targets Cbl-b to activate local, tumor infiltrating lymphocytes (TILs). It is in pre-clinical evaluation for the treatment of patients with glioblastoma.

Thirdly, INV501 is a novel small molecule candidate designed to activate anti-tumour immune responses. It addresses a novel, undisclosed IO target.

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