TRAIL receptor

HEIDELBERG, Germany I June 01, 2023 I Apogenix, a biopharmaceutical company developing next generation immunotherapeutics, announced today that new preclinical data were published in the leading peer-reviewed journal Frontiers in Immunology[1]. In the studies, Apogenix, in collaboration with the group from Professor Tim Illidge at the University of Manchester, UK, demonstrated the therapeutic benefits of the hexavalent CD40 agonist HERA-CD40L in models of prostate cancer refractory to anti-PD-1 therapies, both as monotherapy and in combination with radiotherapy. Importantly, HERA-CD40L was able to significantly reduce tumor growth through a threefold mechanism of action: it increased intratumoral T-cell concentration; modulated the tumor microenvironment (TME) towards a pro-inflammatory state; and reversed the macrophage balance from pro-tumor macrophages (tumor-associated macrophages; TAMs) to anti-tumor macrophages. Thomas Hoeger, PhD, CEO of Apogenix, said: “Immune checkpoint inhibitors have revolutionized cancer treatment, however, the overall response rate for all cancer types in patients is still below twenty percent. New immunotherapeutic strategies are required and with this next-generation HERA-ligand we investigated a potentially viable treatment option – as a monotherapy and in combination with radiotherapy – to improve cancer treatment outcomes.” The full article titled: “The CD40 agonist HERA-CD40L results in enhanced activation of antigen presenting cells, promoting an anti-tumor effect alone and in combination with radiotherapy” can be accessed here. HERA-CD40L is a novel molecule from Apogenix’ platform of hexavalent Tumor Necrosis Factor Receptor Superfamily (TNFRSF) agonists. CD40L is a key regulator of the immune system. The CD40-CD40L immune axis is primarily linked to B cells and is important for sustained antibody production, antibody class switching, and the production of memory B cells. Due to its characteristic of bridging the transition from innate immunity to the initiation of adaptive immunity, CD40 represents a very attractive target for drug development. About Apogenix Apogenix is a private company developing innovative immunotherapeutics for the treatment of cancer and viral infections, such as COVID-19. The company’s pipeline of immunotherapy drug candidates targets different tumor necrosis factor receptor (TNFR) superfamily-dependent signaling pathways in order to restore the anti-tumor immune response in cancer patients and reduce lymphopenia and inflammatory cell death in patients with viral infections. Checkpoint inhibitor asunercept, the company’s lead immunotherapy candidate, is in late-stage clinical development for COVID-19 and glioblastoma with PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of glioblastoma. Based on its proprietary technology platform for the construction of novel TNF superfamily receptor agonists, Apogenix develops CD40 and GITR receptor agonists for cancer immunotherapy. The TRAIL receptor agonist program was out licensed to AbbVie and is currently in clinical phase I trials. About Apogenix’ TNF Receptor Superfamily Agonists (HERA-Ligands) Apogenix has developed a proprietary technology platform for the construction of novel TNF receptor superfamily agonists (HERA-ligands). By stimulating different TNFR signaling pathways, these HERA-ligands can increase the anti-tumor immune response. The specific molecular structure of Apogenix’ HERA-ligands induces a well-defined clustering of functional TNF receptors on the surface of target immune cells. In contrast to agonistic antibodies, Apogenix’ fusion proteins are pure agonists whose potent signaling capacity is independent of secondary Fcγ receptor-mediated crosslinking. In addition, HERA-ligands cause neither antibody-dependent cellular cytotoxicity nor complement-dependent cytotoxicity and exhibit a favorable shorter half-life than antibodies. It is therefore expected that HERA-ligands will cause less side effects in clinical development. [1] https://doi-org.libproxy1.nus.edu.sg/10.3389/fimmu.2023.1160116

Heidelberg, Germany, December 14, 2022 – Apogenix, a biopharmaceutical company developing next generation immunotherapeutics, announced today that the first patients have been enrolled in a pivotal phase III trial to investigate the efficacy and safety of asunercept on top of standard of care (SoC) for the treatment of hospitalized patients with moderate to severe COVID-19 disease (ASUCOV; NCT05639192). The multicenter, double-blind, placebo-controlled trial aims to enroll more than 600 hospitalized patients requiring oxygen in nine different countries. Following the successful controlled ASUNCTIS phase II study, the ASUCOV trial aims to confirm the clinical results in a larger study population. The primary endpoint is the efficacy measured as time to sustained recovery with an improvement of at least two grades on the WHO clinical progression scale for at least two consecutive days or discharge from hospital. The secondary endpoints of the ASUCOV trial assess the reduction of progression to more severe disease, all-cause mortality, and progression to invasive ventilation. Thomas Hoeger, PhD, Chief Executive Officer of Apogenix, said: “After the encouraging results of our phase II ASUNCTIS trial we are very pleased to take this next important step that will pave the way towards regulatory approval of asunercept. We hope to provide an effective treatment option for hospitalized COVID-19 patients because we still see too many deaths worldwide. As asunercept is expected to prevent disease progression and reduce the number of COVID-19 patients who require intensive care or die from this disease, we believe that this treatment could become an attractive therapeutic option.” CD95 ligand mediated dysregulation of the immune homeostasis by induction of apoptotic cell death has been observed in various diseases and might be a key driver for reduced lymphocyte counts (lymphopenia) and massive lung tissue damage during progression of COVID-19. Currently, there are no approved treatments that could re-balance the immune system and prevent disease deterioration. Especially elderly patients with co-morbidities still face high mortality rates and are in urgent need of new treatments. Asunercept, a CD95 ligand (CD95L) inhibitor, represents a novel and unique therapeutic approach for COVID-19 and other viral infections. As asunercept is not targeting the virus itself, treatment with asunercept is independent of viral strains. The ASUCOV pivotal trial and related activities are funded with 20.7m EUR by the German Federal Government through grant number 16LW0102 as well as Apogenix’ lead investor dievini Hopp BioTech Holding GmbH & Co. KG. All responsibility for the content of this work lies with Apogenix. About Apogenix Apogenix is a private company developing innovative immunotherapeutics for the treatment of cancer and viral infections, such as COVID-19. The company’s pipeline of immunotherapy drug candidates targets different tumor necrosis factor (TNF) superfamily-dependent signaling pathways in order to restore the anti-tumor immune response in cancer patients and reduce lymphopenia and lung epithelial cell death in patients with viral infections. Checkpoint inhibitor asunercept, the company’s lead immunotherapy candidate, is in late-stage clinical development for COVID-19 and glioblastoma. PRIME (PRIority MEdicines) designation has been granted by the European Medicines Agency for the treatment of glioblastoma. Based on its proprietary technology platform for the construction of novel TNF superfamily receptor agonists, Apogenix develops CD40 and GITR receptor agonists for cancer immunotherapy. The TRAIL receptor agonist program was out licensed to AbbVie and is currently in clinical phase I trials. About Asunercept Apogenix’ lead immunotherapy candidate asunercept is a fully human fusion protein that consists of the extracellular domain of the CD95 receptor and the Fc domain of an IgG1 antibody. It is being developed for the treatment of solid tumors and viral infections, such as COVID-19. Asunercept was granted orphan drug designation for the treatment of glioblastoma and myelodysplastic syndromes (MDS) in both the EU and the US and PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of glioblastoma. For the region China, Macao, Hong Kong, and Taiwan, Asunercept is exclusively licensed to CANbridge Life Sciences under a development and commercialization agreement.

Clinical efficacy demonstrated for all asunercept dose groups Statistically significant faster clinical recovery for combined treatment groups compared to control group Excellent safety pro asunercept confirmed Pivotal phase III study initiated Heidelberg, Germany, October 19, 2022 – Apogenix, a biopharmaceutical company developing next generation immunotherapeutics, announced today that asunercept showed statistically significant benefits for hospitalized COVID-19 patients in the ASUNCTIS trial. The open-label multi-center phase II trial investigated efficacy and safety of asunercept in 435 patients with moderate to severe COVID-19 disease. COVID-19 patients were randomized equally into four study arms, receiving 25, 100, or 400 mg asunercept (once weekly, i.v.) on top of standard of care (SOC), respectively, or SOC alone. Efficacy was assessed against the WHO-suggested endpoints, including time to clinical improvement according to WHO scale and mortality. The results show strong trends for clinical efficacy in all treatment groups, indicating a robust activity of asunercept. Consistently, patients showed faster clinical improvement by approximately 40 % compared to the control group (8-9 days for the three different treatment groups vs. 13 days with SOC). The combined asunercept dose groups (25, 100 and 400 mg arms) revealed statistically significant faster clinical improvement compared to SOC group (p= 0.038; HR=1.37). Statistical significance was closely missed when comparing the individual treatment groups with SOC group. Furthermore, the pre-specified analysis of patients with WHO score 4 (n=342) at the beginning of the trial showed an approximately 40 % faster clinical improvement in all asunercept groups compared to control. In these patients, a statistically significant clinical benefit for the 100 mg asunercept group (n=83) could be achieved (p=0.044; HR=1.53). All patients receiving asunercept showed a marked reduction of all-cause mortality at all time points and for each dose compared to patients receiving SOC. Furthermore, asunercept reduces the time to recovery from lymphopenia, confirming its presumed mechanism of action. As the extent of lymphopenia correlates with severity of the COVID-19 disease, asunercept accelerates recovery from disease. Safety in all asunercept plus SOC treatment arms was comparable to the SOC arm, confirming the favorable safety pro asunercept observed in all previous clinical trials. No trend or pattern was identified among serious and non-serious adverse events across all treatment arms. Apogenix intends to publish detailed results from this study in a peer-reviewed journal. Univ.-Prof. Felix JF Herth, MD, PhD, Chairman and Head Department of Pneumology and Critical Care Medicine at Thoraxklinik University of Heidelberg and Chairman of the Data Safety Monitoring Board (DSMB) of the ASUNCTIS trial, commented: “Despite some progress in the treatment of hospitalized COVID-19 patients requiring additional oxygen, there still remains a high unmet medical need for this patient group. Asunercept is a novel immune-modulating treatment approach which seems to work independently of COVID-19 strains. It combines an excellent safety pro encouraging efficacy data, warranting the advancement of clinical development and initiation of a pivotal phase III study.” Thomas Hoeger, PhD, Chief Executive Officer of Apogenix, said: “We are very pleased to see asunercept displaying a robust efficacy and favorable safety pro the ASUNCTIS trial. Asunercept is expected to prevent the death of immune and lung cells leading to lymphopenia and acute respiratory distress syndrome, thus reducing the number of COVID-19 patients who require intensive care or even die from this disease. Based on our promising phase II results and given the high need for effective COVID-19 medication in hospitalized patients, we are initiating a pivotal phase III trial (ASUCOV) with asunercept to confirm the encouraging results in a larger number of patients.” The ASUCOV pivotal trial and related activities are funded with 20.7m EUR by the German Federal Government through grant number 16LW0102 as well as by Apogenix’ leading investor dievini Hopp BioTech Holding GmbH & Co. KG. All responsibility for the conduct of this project of this work lies with Apogenix. About Apogenix Apogenix is a private company developing innovative immunotherapeutics for the treatment of cancer and viral infections, such as COVID-19. The company’s pipeline of immunotherapy drug candidates targets different tumor necrosis factor (TNF) superfamily-dependent signaling pathways in order to restore the anti-tumor immune response in cancer patients and reduce lymphopenia and inflammatory cell death in patients with viral infections. Checkpoint inhibitor asunercept, the company’s lead immunotherapy candidate, is in late-stage clinical development for COVID-19 and glioblastoma with PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of glioblastoma. Based on its proprietary technology platform for the construction of novel TNF superfamily receptor agonists, Apogenix develops CD40 and GITR receptor agonists for cancer immunotherapy. The TRAIL receptor agonist program was out licensed to AbbVie and is currently in clinical phase I trials. About Asunercept Apogenix’ lead immunotherapy candidate asunercept is a fully human fusion protein that consists of the extracellular domain of the CD95 receptor and the Fc domain of an IgG1 antibody. It is being developed for the treatment of solid tumors, hematological malignancies, and viral infections, such as COVID-19. Asunercept was granted orphan drug designation for the treatment of glioblastoma and myelodysplastic syndromes (MDS) in both the EU and the US and PRIME (PRIority MEdicines) designation by the European Medicines Agency for the treatment of glioblastoma. Asunercept is exclusively licensed to CANbridge Life Sciences under a development and commercialization license covering China, Macao, Hong Kong, and Taiwan. Apogenix acted as sponsor of the ASUNCTIS phase II study. The clinical study protocol has been developed together with Prof. Walczak, University of Cologne, Prof. Bergmann and colleagues, Medical University Vienna and Dr. Pilar Ruiz Seco, Hospital Infanta Sofia, Spain. Contacts Media Contacts Thomas Hoeger, Ph.D., CEO Katja Arnold Judith Teumer, PR Dr. Brigitte Keller Apogenix AG MC Services AG Phone: +49 6221 58608-0 Phone: +49 89 210228-0 E-Mail: contact@apogenix.com E-Mail: apogenix@mc-services.eu Web: