Metastatic Appendix Carcinoma

Multi-center trial of novel autologous cell therapy APN401 leveraging two GMP-compliant manufacturing sites has received regulatory approval and patient recruitment has started; invIOs awarded up to 45% funding of trial costs by Austrian Research Promotion Agency (FFG) to support Phase 1b RP2D trial; invIOs recently also awarded grant funding to advance novel CAR-T cell therapy INV451 against lung cancer with Medical University of Innsbruck. VIENNA, Austria, Sept. 05, 2023 (GLOBE NEWSWIRE) -- invIOs GmbH (“invIOs”), a privately held biotechnology company developing novel therapies for cancer, today 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. PALINDROM is a multi-center trial taking place in Austria with two GMP-compliant manufacturing sites in Vienna and Linz. The trial will evaluate two dosage levels of APN401 infusions in up to 12 patients across four clinics, focusing on the treatment’s tolerability, safety and clinical activity in patients with advanced and metastatic solid tumors for whom established standard therapies have either become ineffective or are not suitable. 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. The study, which will be carried out under the EU’s new Clinical Trial Regulation, has received regulatory approval from the Austrian Agency for Health and Food Safety (AGES). Patient recruitment has started, and invIOs aims to complete enrollment by the end of the year. “I am delighted that the Austrian government is supporting our latest clinical trial using the EPiC cell therapy platform to develop an innovative and potentially game-changing approach to treating solid tumors,” said Peter Llewellyn-Davies, CEO of invIOs. “The Austrian Life Sciences Programme is a massive boost for the wider Austrian biotech industry and in particular for invIOs, as we continue to make strong progress across our three EPiC-based programs.” Dr. Romana Gugenberger, Chief Medical and Scientific Officer of invIOs, added: “We have already demonstrated the safety and technical feasibility of our EPiC cell therapy platform technology that underpins APN401 in first-in-human clinical trials. This new study aims to show that EPiC can be effective when multiple manufacturing and treatment sites are involved. We look forward to taking this novel, easy-to-administer treatment option to the next phase of development.” The primary endpoint of the PALINDROM study is to define and confirm the safety pro APN401. Secondary endpoints will include measures of immunological and anti-tumor activity, including overall response rate (ORR) and progression-free survival (PFS), as well as analysis of relevant biomarkers. 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. APN401 is an innovative approach that leverages invIOs’s proprietary EPiC cell therapy platform to transfect autologous peripheral blood mononuclear cells (PBMCs) with siRNA to silence Cbl-b, which belongs to a class of proteins found in immune cells that are known to play a key role in inhibiting immune responses against cancer. By transiently blocking Cbl-b it is possible to overcome the immunosuppressive tumor microenvironment (TME) and enhance killing of tumor cells and also to induce prolonged anti-tumor immune cell memory. As an individualized treatment, APN401 educates and empowers the patient’s own most recent immune cells to detect and attack tumor cells. Previous pilot trials have shown the potential clinical benefits of the treatment including rapid cell manufacturing, short vein-to-vein time, tumor-agnostic applicability and very good tolerability. invIOs earlier this year announced promising clinical data from a Phase 1 study suggesting clinical activity of APN401 in two heavily pre-treated patients, one with metastatic appendix carcinoma and one with squamous cell carcinoma of the head and neck, who achieved stable disease for up to six months during treatment. The study further demonstrated that the EPiC platform represents a feasible approach for rapid local manufacturing of a Cbl-b silenced cell therapy, enabling out-patient treatment of patients with advanced solid tumors with vein-to-vein times of less than 24 hours. In addition to the funding for the PALINDROM study, invIOs also recently secured a grant from the FFG to progress a novel CAR-T cell therapy approach leveraging the EPiC platform against aggressive lung tumors in a joint project with the Medical University of Innsbruck. The INV451 project is invIOs’s third program from the EPiC platform. The project aims to refine and enhance the efficacy of CAR-T cell therapies against solid tumors by discovering additional insights into the mechanisms that tumors use to escape detection and evade destruction by the immune system, and hence to identify druggable factors that can overcome resistance to treatment. About invIOs invIOs is a privately held biotech company based in Vienna, Austria, focusing on the discovery and development of novel therapies for cancer. The invIOs team leverages deep expertise in immune system activation to develop individualized and targeted approaches against solid tumors. invIOs is advancing a pipeline of three programs encompassing small molecule and cell therapy approaches. EPiC, invIOs’s proprietary cell therapy platform, enables rapid treatment of patients in an out-patient setting. EPiC is a technology platform that allows the creation of personalized cell therapies based on localized processing of a patient’s fresh immune cells. The first asset from the EPiC platform, APN401, is in Phase 1 clinical trials against various solid tumors. The second asset, INV441, is being developed against glioblastoma and is in preclinical evaluation. The third EPiC program, INV451, is a novel CAR-T cell approach against lung cancer being developed with the Medical University of Innsbruck. INV501 is a novel small molecule candidate that can selectively enhance anti-tumor immune responses. It induces T cell activation, proliferation, and tumor-reactive cytotoxicity. An orally available compound with good bioavailability, INV501 is currently in preclinical testing in several solid tumor models and has demonstrated preclinical proof of concept with strong data in multiple solid tumor indications. For further information, please visit and connect with us on LinkedIn. Contacts invIOs Peter Llewellyn-Davies CEO/CFO T +43 1 8656577 0 Email: investors@invios.com MC Services AG Raimund Gabriel, Dr. Regina Lutz, Laurie Doyle T +49 89 210 228 0 Email: invios@mc-services.eu

Multi-center trial of novel autologous cell therapy APN401 leveraging two GMP-compliant manufacturing sites has received regulatory approval and patient recruitment has started; invIOs awarded up to 45% funding of trial costs by Austrian Research Promotion Agency (FFG) to support Phase 1b RP2D trial; invIOs recently also awarded grant funding to advance novel CAR-T cell therapy INV451 against lung cancer with Medical University of Innsbruck. Vienna, Austria, 5 September 2023: invIOs GmbH (“invIOs”), a privately held biotechnology company developing novel therapies for cancer, today 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. PALINDROM is a multi-center trial taking place in Austria with two GMP-compliant manufacturing sites in Vienna and Linz. The trial will evaluate two dosage levels of APN401 infusions in up to 12 patients across four clinics, focusing on the treatment’s tolerability, safety and clinical activity in patients with advanced and metastatic solid tumors for whom established standard therapies have either become ineffective or are not suitable. 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. The study, which will be carried out under the EU’s new Clinical Trial Regulation, has received regulatory approval from the Austrian Agency for Health and Food Safety (AGES). Patient recruitment has started, and invIOs aims to complete enrollment by the end of the year. “I am delighted that the Austrian government is supporting our latest clinical trial using the EPiC cell therapy platform to develop an innovative and potentially game-changing approach to treating solid tumors,” said Peter Llewellyn-Davies, CEO of invIOs. “The Austrian Life Sciences Programme is a massive boost for the wider Austrian biotech industry and in particular for invIOs, as we continue to make strong progress across our three EPiC-based programs.” Dr. Romana Gugenberger, Chief Medical and Scientific Officer of invIOs, added: “We have already demonstrated the safety and technical feasibility of our EPiC cell therapy platform technology that underpins APN401 in first-in-human clinical trials. This new study aims to show that EPiC can be effective when multiple manufacturing and treatment sites are involved. We look forward to taking this novel, easy-to-administer treatment option to the next phase of development.” The primary endpoint of the PALINDROM study is to define and confirm the safety profile of APN401. Secondary endpoints will include measures of immunological and anti-tumor activity, including overall response rate (ORR) and progression-free survival (PFS), as well as analysis of relevant biomarkers. 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. APN401 is an innovative approach that leverages invIOs’s proprietary EPiC cell therapy platform to transfect autologous peripheral blood mononuclear cells (PBMCs) with siRNA to silence Cbl-b, which belongs to a class of proteins found in immune cells that are known to play a key role in inhibiting immune responses against cancer. By transiently blocking Cbl-b it is possible to overcome the immunosuppressive tumor microenvironment (TME) and enhance killing of tumor cells and also to induce prolonged anti-tumor immune cell memory. As an individualized treatment, APN401 educates and empowers the patient’s own most recent immune cells to detect and attack tumor cells. Previous pilot trials have shown the potential clinical benefits of the treatment including rapid cell manufacturing, short vein-to-vein time, tumor-agnostic applicability and very good tolerability. invIOs earlier this year announced promising clinical data from a Phase 1 study suggesting clinical activity of APN401 in two heavily pre-treated patients, one with metastatic appendix carcinoma and one with squamous cell carcinoma of the head and neck, who achieved stable disease for up to six months during treatment. The study further demonstrated that the EPiC platform represents a feasible approach for rapid local manufacturing of a Cbl-b silenced cell therapy, enabling out-patient treatment of patients with advanced solid tumors with vein-to-vein times of less than 24 hours. In addition to the funding for the PALINDROM study, invIOs also recently secured a grant from the FFG to progress a novel CAR-T cell therapy approach leveraging the EPiC platform against aggressive lung tumors in a joint project with the Medical University of Innsbruck. The INV451 project is invIOs’s third program from the EPiC platform. The project aims to refine and enhance the efficacy of CAR-T cell therapies against solid tumors by discovering additional insights into the mechanisms that tumors use to escape detection and evade destruction by the immune system, and hence to identify druggable factors that can overcome resistance to treatment. About invIOs invIOs is a privately held biotech company based in Vienna, Austria, focusing on the discovery and development of novel therapies for cancer. The invIOs team leverages deep expertise in immune system activation to develop individualized and targeted approaches against solid tumors. invIOs is advancing a pipeline of three programs encompassing small molecule and cell therapy approaches. EPiC, invIOs’s proprietary cell therapy platform, enables rapid treatment of patients in an out-patient setting. EPiC is a technology platform that allows the creation of personalized cell therapies based on localized processing of a patient’s fresh immune cells. The first asset from the EPiC platform, APN401, is in Phase 1 clinical trials against various solid tumors. The second asset, INV441, is being developed against glioblastoma and is in preclinical evaluation. The third EPiC program, INV451, is a novel CAR-T cell approach against lung cancer being developed with the Medical University of Innsbruck. INV501 is a novel small molecule candidate that can selectively enhance anti-tumor immune responses. It induces T cell activation, proliferation, and tumor-reactive cytotoxicity. An orally available compound with good bioavailability, INV501 is currently in preclinical testing in several solid tumor models and has demonstrated preclinical proof of concept with strong data in multiple solid tumor indications. For further information, please visit www.invios.com and connect with us on LinkedIn. Contacts invIOs Peter Llewellyn-Davies CEO/CFO T +43 1 8656577 0 Email: investors@invios.com MC Services AG Raimund Gabriel, Dr. Regina Lutz, Laurie Doyle T +49 89 210 228 0 Email: invios@mc-services.eu

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 Phase 1b clinical study demonstrated feasibility of integrating into daily clinical practice VIENNA, Austria, April 18, 2023 (GLOBE NEWSWIRE) -- invIOs GmbH (“invIOs”), a privately held biotechnology company developing novel therapies for cancer, today announced data from a poster showing two patient case studies from a clinical trial of its lead candidate cell therapy APN401 during the American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida. The poster, “APN401, a novel cancer therapy using Cbl-b silenced autologous PBMCs, induced stable disease in two patients with advanced solid tumors”, highlights two cases of heavily pre-treated patients, one diagnosed with metastatic appendix carcinoma and one diagnosed with squamous cell carcinoma of the head and neck. Both patients were part of invIOs’s recently completed Phase 1b trial and achieved stable disease for up to 6 months during treatment with APN401. Dr Romana Gugenberger, CMSO of invIOs, said: “We believe that our approach based on silencing the master immune system checkpoint Cbl-b could have a significant impact on the development of effective cell therapy treatments for solid tumors, and make these cancers vulnerable to anti-tumor immune responses. These two case studies from our successfully completed clinical trial demonstrate APN401’s potential in patients with advanced metastatic disease whose cancer had progressed despite numerous previous treatments. In addition, the study confirmed that invIOs’s cell therapy platform represents a feasible approach for rapid local manufacturing of a Cbl-b silenced cell therapy, enabling out-patient treatment with vein-to-vein times of less than 24 hours. The promising results of this study open the door to continuing further development of the APN401 program in earlier lines of treatment, including as a combination therapy.” The patient with metastatic appendix carcinoma was treated with 12 treatment cycles over the course of 44 weeks and presented with stable disease for 27 weeks, while the patient with metastatic head and neck cancer received six treatment cycles over 20 weeks and was progression-free for 22 weeks, suggesting immunological anti-tumor activity. This is further supported by analysis of both patients’ Cbl-b silenced PBMCs (peripheral blood mononuclear cells), which showed increased cytotoxic capacity and increased potency. Furthermore, analysis of the patients’ T cells before each infusion cycle showed an increase in T cell clonality during the treatment period. In both cases, the treatment was well tolerated. Professor Thorsten Füreder, program director for respiratory tract cancers and cancer of unknown primary at the Department of Medicine I, Medical University of Vienna, chair of the university’s immune-oncology tumor board, and an investigator on the study, said: “From a clinical perspective, the therapy of heavily pre-treated recurrent/metastatic HNSCC patients remains a challenge, since the majority of patients show progressive disease and can expect progression-free survival of approximately just 2 months. In this context, disease stabilization for almost 5.5 months in a recurrent/metastatic HNSCC patient treated with APN401 is an encouraging signal and clinically relevant. Larger trials beyond the case series are now needed to derive a definitive conclusion regarding the clinical activity of this novel approach.” About APN401 and invIOs’s proprietary cell therapy platform APN401 leverages invIOs’s proprietary cell therapy platform, which enables rapid treatment of patients with personalized cell therapies, and holds the promise to be effective against even solid tumors. The technology has the potential to be used with a range of approaches such as siRNA or mRNA, or combinations of modalities to target expression of multiple genes and create next-generation cancer immunotherapies. APN401 is designed to supercharge immune cells to fight tumors by overriding multiple immune checkpoints via silencing Cbl-b (Casitas B-lineage lymphoma b), which is regarded as a master checkpoint of the immune system. Cbl-b deficiency can make cells resistant to the inhibitory signals from both CTLA-4 and PD-L1/PD-1 checkpoints, which are used by many solid tumors for immune evasion. APN401 uses small interfering RNA (siRNA) to silence Cbl-b in the patients’ PBMCs. Typical vein-to-vein time for each treatment cycle with APN401 is 24 hours, with cell processing taking just six hours using invIOs’s proprietary closed, modular, automated and highly scalable system. About invIOs invIOs is a privately held biotech company based in Vienna, Austria, focusing on the discovery and development of innovative cancer immunotherapies. invIOs’s proprietary cell therapy platform for intracellular modification of gene expression enables rapid treatment of patients in an out-patient setting through the creation of personalized cell therapies using a patient’s fresh immune cells. Once clinically validated, this novel concept may allow access to and treatment for indications not previously addressable by immunotherapy. APN401 is the first candidate treatment from invIOs’s cell therapy platform. It is a first-in-class out-patient approach to strengthen immune reactivity by targeting the intracellular master checkpoint inhibitor Cbl-b. A second Phase 1b clinical trial in patients with advanced solid tumors has recently been completed. INV441, the second candidate from invIOs’s 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. INV501 is a novel small molecule candidate designed to address a new, undisclosed immune-oncology target to activate strong anti-tumor immune responses. The program is currently in pre-clinical testing. For further information, please visit and connect with us on LinkedIn. Contacts invIOs Peter Morley Head of Communications T +43 1 8656577 121 Email: investors@invios.com MC Services AG Raimund Gabriel, Dr. Regina Lutz, Laurie Doyle T +49 89 210 228 0 Email: invios@mc-services.eu