Intuvax (ilixadencel) / Mendus - LARVOL DELTA

The advantages of NK cell vaccines in solid carcinoma clinical trials: conducted by various biology strategy and technology. (PubMed, Front Med (Lausanne)) - "The study illustrated: Dendritic cell-based vaccine platforms (e.g., ilixadencel), cytokine-based vaccine platforms (e.g., ALT-803), NK receptor agonist antibodies (e.g., AFM24) and mRNA/LNP-based vaccine platforms (e.g., BNT116) It has shown early efficacy in solid tumors such as non-small cell lung cancer, triple-negative breast cancer, and glioblastoma (with partial ORR of 30-50% and DCR of 80-100%), and the safety is comparatively manageable (the incidence of grade ≥3 adverse events is less compared to T-cell therapy). In the future, combinatorial regimens (e.g., sequential application of PD-1 inhibitors) need to be optimized, an iPSC-NK universal platform developed, and perioperative application scenarios explored. NK vaccines, by reshaping the immune microenvironment, will be an attractive strategy to break the bottlenecks in the treatment of solid tumors."

Journal • Review • Brain Cancer • Breast Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Positive preclinical results for Immunicum (BioStock) - "The results showed that animals treated with ilixadencel + anti-CTLA-4 demonstrated a stronger anti-tumour response compared to animals treated with the well-established combination PD-1 and CTLA-4."

Preclinical • Solid Tumor

Mendus announces termination by Institut Bergonié of the collaboration agreement to study ilixadencel in soft tissue sarcomas (Mendus Press Release) - "Mendus AB...announces that Institut Bergonié has terminated the collaboration agreement with Mendus, because it is no longer in a position to study Mendus’ intratumoral immune primer ilixadencel in soft tissue sarcomas as part of the REGOMUNE trial. Mendus has decided to not pursue new clinical trials and to explore alternative strategic options for the ilixadencel program....Due to evolving business needs, Bayer AG will no longer support the REGOMUNE trial and Institut Bergonié is therefore no longer in a position to open new study cohorts for the trial. As a consequence of the termination of the collaboration agreement with Institut Bergonié and in the light of the positive data with its lead program vididencel, Mendus has decided to not pursue new clinical trials with ilixadencel and to focus its clinical development strategy on vididencel."

Commercial • Soft Tissue Sarcoma

The intratumoral immune primer ilixadencel acts synergistically with the anti-PD-L1 antibody avelumab (SITC 2024) - "Methods Ilixadencel DCs were co-cultured with allogeneic peripheral blood mononuclear cells (PBMCs) at a ratio 1:5 for 48 hours, +/- avelumab, atezolizumab (anti-PD-L1 antibody with a non-agonistic Fc-domain) or pembrolizumab targeting programmed cell death protein 1 (PD-1). This may promote increased intratumoral recruitment and activation/maturation of endogenous immune cells, including cross-presenting DCs, subsequently leading to increased priming and expansion of tumor-specific T cells. The data therefore support the exploration of a combination therapy comprising ilixadencel and avelumab for the treatment of solid tumors."

IO biomarker • Oncology • Solid Tumor • CCR7 • CD83 • CD86 • IFNG • PD-1 • TNFA • TNFRSF9

Phase I study of allogeneic monocyte-derived inflammatory dendritic cells in combination with pembrolizumab. (PubMed, Future Sci OA) - "We hypothesized that ilixadencel, an allogeneic monocyte-derived dendritic cell product could be injected into tumor to potentiate PD-1 response and thus conducted a phase I study of pembrolizumab plus ilixadencel. No dose limiting toxicities were observed and the recommended phase II dose was established at 10 million cells administered twice. Two unconfirmed responses were observed, with no confirmed responses."

Combination therapy • Journal • P1 data • Cardiovascular • Fatigue • Head and Neck Cancer • Heart Failure • Hematological Disorders • Oncology • Pain • Solid Tumor

Mendus to present preclinical data supporting the combination potential of ilixadencel with the immune checkpoint inhibitor avelumab at SITC 2024 (Mendus Press Release) - "Mendus will present preclinical data demonstrating that ilixadencel and avelumab act synergistically in intratumoral priming of the immune system during the 39th annual meeting of the Society for Immunotherapy of Cancer (SITC), held November 6-10, 2024 (SITC 2024). Addition of avelumab leads to stronger natural killer cell activation by ilixadencel, enhances production of proinflammatory cytokines and chemokines in ilixadencel-stimulated peripheral blood mononuclear cells and leads to improved maturation of bystander dendritic cells."

Preclinical • Oncology • Solid Tumor

Mendus announces clinical pipeline update (GlobeNewswire) - P2 | N=88 | MERECA (NCT02432846) | Sponsor: Mendus | "Mendus reports completion of the long-term follow up of the MERECA trial studying the intratumoral immune primer ilixadencel in metastatic renal cell carcinoma (mRCC). The long-term follow up data confirmed the observations previously reported, with no significant survival difference between the ilixadencel plus sunitinib treatment arm versus the sunitinib-only control arm of the trial. The final results of the MERECA trial confirm the decision not to pursue mRCC as a possible indication for ilixadencel. Mendus continues to explore the clinical development of ilixadencel in soft tissue sarcomas (STS) in the first half of 2024, versus earlier guidance of starting a trial before 2023YE."

New trial • P2 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Mendus AB Interim Report January – September 2023 (GlobeNewswire) - "In Q3, Mendus has taken the first steps in implementing the manufacturing alliance with NorthX Biologics, a leading Nordic contract development and manufacturing organization for cell and gene therapies. Large-scale, commercial-grade manufacturing is an important step for late-stage clinical development of vididencel and NorthX will therefore be a significant partner for Mendus going forward....Recruitment of the ALISON trial (n = 17) is nearly complete with 16 patients having entered the trial and is expected to close before year-end 2023. Next read-outs of the ALISON trial are expected in the first half of 2024....Mendus’ second clinical-stage program ilixadencel is ready to be tested in a proof-of- concept trial based on initial positive data observed in gastrointestinal stromal tumors (GIST). There is continued clinical interest in pursuing a trial with ilixadencel in soft-tissue sarcomas, of which GIST is a subtype. The trial is expected to commence before year-end 2023."

Enrollment status • Licensing / partnership • New trial • P1 data • Acute Myelogenous Leukemia • Gastrointestinal Stromal Tumor • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Proinflammatory allogeneic dendritic cells enhance the therapeutic efficacy of systemic anti-4-1BB treatment. (PubMed, Front Immunol) - "Additionally, the combined treatment resulted in a less immunosuppressive TME, indicated by decreased infiltration of myeloid-derived suppressor cells and Tregs. These findings suggest that the combination of intratumoral AlloDCs administration with systemic agonistic α4-1BB treatment can generate a synergistic anti-tumor response, thereby warranting further investigation through clinical studies."

Journal • Colon Cancer • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • CD69 • CD8 • IFNG • ITGA1 • ITGAE

Mendus publishes preclinical data demonstrating synergies of ilixadencel and 4-1BB-targeting immunotherapies (GlobeNewswire) - "Mendus AB...announced the publication of novel preclinical data on its intratumoral priming strategy in the peer-reviewed medical journal ‘Frontiers in Immunology’. The data demonstrate the potential of proinflammatory allogeneic dendritic cells to significantly enhance the therapeutic efficacy of an anti-4-1BB antibody, delaying tumor growth and prolonging survival in murine colon carcinoma and melanoma models. Investigation of the tumor microenvironment (TME) in the combined-treatment group revealed a range of improvements resulting in a less immunosuppressive TME, with elevated tumor-infiltration of therapeutically valuable T-cell populations observed....Mendus is currently preparing for a proof-of-concept trial with ilixadencel in the broader group of soft tissue sarcomas in H2 2023."

New trial • Preclinical • Colon Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor

Mendus AB: Mendus AB (publ) Interim Report July – September 2022 (GlobeNewswire) - "We published promising data studying the combination of ilixadencel with CTLA-4 checkpoint inhibition and presented preclinical data demonstrating the synergistic combination of vaccination and intratumoral immune priming in an ovarian cancer model at ESGO. Data demonstrating the potential of the DCOne platform to selectively expand memory natural killer cells as the basis for potential novel NK cell therapies were very recently presented at the SITC conference. Our preclinical research lies the foundation for new proprietary pipeline projects and commercial opportunities in 2023 and beyond....Mendus reported positive clinical and preclinical data in ovarian cancer at the European Society of Gynaecological Oncology (ESGO) conference held October 27-30, 2022....Mendus presented data demonstrating the potential of the DCOne platform to expand memory NK cells for therapeutic purposes at the Society for Immunotherapy of Cancer (SITC) conference held November 10-12, 2022."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer

A randomized phase 2 study with a cell-based immune primer plus sunitinib versus sunitinib aone in metastatic Renal Cell Carcinoma. (IKCS 2022) - "The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher response rate, including longstanding CRs, compared with sunitinib monotherapy, suggesting an immunologic effect of the experimental treatment."

Clinical • P2 data • Genito-urinary Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Renal Cell Carcinoma • Solid Tumor

Intratumoral administration of pro-inflammatory allogeneic dendritic cells improved the anti-tumor response of systemic anti-CTLA-4 treatment via unleashing a T cell-dependent response. (PubMed, Oncoimmunology) - "Moreover, splenocytes from mice in the combination treatment group secreted significantly higher IFN-γ upon stimulation with the peptide from the endogenous CT-26 retroviral gp70 (model neoantigen), confirming the induction of a tumor-specific CD8 T-cell response. Taken together, these data indicate a strong anti-tumor synergy between AlloDCs and αCTLA-4 that warrant further clinical investigation with the corresponding human AlloDC product (ilixadencel) for patients receiving αCTLA-4 therapy."

Journal • Immune Modulation • Inflammation • Oncology • CD8 • CX3CR1 • IFNG • ITGAE

Mendus Publishes Preclinical Data Demonstrating Significant Anti-Tumor Synergies of Intratumoral Immune Priming with CTLA-4 Inhibition (GlobeNewswire) - "Neither ilixadencel, nor anti-CTLA-4 treatment alone affected tumor progression or prolonged survival significantly. However, combined treatment with ilixadencel and anti-CTLA-4 significantly delayed tumor progression and led to tumor remission with 7 out of 10 mice surviving longer than 70 days with no detectable tumor....Several findings of the study demonstrated a profound remodeling of the initially immunosuppressive tumor microenvironment following the combined use of ilixadencel and the anti-CTLA-4 inhibitor. Changes to the TME were visible in gene set analyses of significant pathway signatures including upregulated pathways that affect the myeloid compartment, antigen presentation, the lymphoid compartment, and cytokines/chemokine regulation."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Immunicum AB: Immunicum Received FDA Orphan Drug Designation for Ilixadencel as Treatment of Gastrointestinal Stromal Tumors (GIST) (GlobeNewswire) - "Immunicum AB...announced today that it has been granted an Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for ilixadencel in the treatment of Gastrointestinal Stromal Tumors (GIST)."

Orphan drug • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Soft Tissue Sarcoma

Ilixadencel, a Cell-based Immune Primer, plus Sunitinib Versus Sunitinib Alone in Metastatic Renal Cell Carcinoma: A Randomized Phase 2 Study. (PubMed, Eur Urol Open Sci) - "We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect."

Journal • P2 data • Genito-urinary Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Renal Cell Carcinoma • Solid Tumor

Immunicum AB: Immunicum AB (publ) Interim Report January – March 2022 (GlobeNewswire) - "Immunicum provided a pipeline and strategy outlook. In 2022, the clinical development focus will be on i) the continuation and further clinical data updates of the ADVANCE II study evaluating DCP-001 in the acute myeloid leukemia (AML) maintenance setting, ii) the continuation of the ALISON study in ovarian cancer, which will deliver a first clinical read-out in 2022 and iii) the evaluation and preparation of the TROY study, which will evaluate Ilixadencel’s potential in gastrointestinal stromal tumors (GIST)."

Clinical • P1 data • Acute Myelogenous Leukemia • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hematological Malignancies • Oncology

Immunicum AB: Immunicum Publishes Phase II MERECA Trial Results of Ilixadencel in Kidney Cancer in European Urology Open Sciences (GlobeNewswire) - P2 | N=88 | MERECA (NCT02432846) | Sponsor: Immunicum AB | "The 18 months survival rate as primary endpoint of the study showed no significant differences between combination arm and control group. However, the median OS was 35.6 months for the ilixadencel + sunitinib combination arm, as compared to 25.3 months in the control group, showing an improved survival over time....Confirmed ORR was 42.2 % (19 out of 45) in the combination arm, including 3 patients with confirmed complete response (CR). Two additional patients in the combination arm developed a CR at the last follow-up CT scan at 18 months (non-confirmed CR). The ORR in the control group was 24.0% (6 out of 25) with no confirmed CR. One patient in the control arm had a CR observed at the last 18-months CT follow-up. The five patients who achieved a CR in the combination arm were all still alive at the latest survival follow up while the one patient with a non-confirmed CR in the control group had died."

P2 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

ILIAD: A Study to Evaluate the Safety and Effectiveness of ILIxadencel Administered Into Tumors in Combination With Checkpoint Inhibitor (CPI) in Patients With ADvanced Cancer (clinicaltrials.gov) - P1b/2 | N=21 | Terminated | Sponsor: Immunicum AB | N=150 ➔ 21 | Trial completion date: Jul 2023 ➔ Dec 2021 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2022 ➔ Dec 2021; Decision made not to move to Phase 2

Checkpoint inhibition • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis. (PubMed, Acta Radiol) - "DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC."

Clinical • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • MRI

Immunicum Announces Completion of Phase Ib Portion and Early Closure of ILIAD Study (GlobeNewswire) - P1/2, N=150; ILIAD (NCT03735290); Sponsor: Immunicum AB; "Immunicum AB...announced today the completion of the Phase Ib portion of the ILIAD study evaluating the Company’s off-the-shelf, cell-based immune primer ilixadencel in combination with anti-PD1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda®) in different cancer indications. All subjects in the Phase Ib portion have completed the initial follow-up period for safety and response evaluation, with a positive safety review by the Data Safety Monitoring Board reported last July. Responses to treatment were observed in patients previously treated with CPIs and not in CPI-naive patients...Of the five patients that were enrolled in the Phase Ib portion of the ILIAD study without any prior exposure to pembrolizumab, none had any observable response...'The data from the ILIAD study will further support our decision making around future clinical studies, on which we will provide an update in the first quarter of 2022."

P1/2 data • Trial status • CNS Tumor • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

Immunicum AB (publ) Interim Report July - Sep 2021 (GlobeNewswire) - "Immunicum is preparing to present an update on the fully enrolled ADVANCE II study at the American Society for Hematology meeting (ASH), to be held in December 2021....Immunicum continues to invest in process development for both of its lead programs, DCP-001 and ilixadencel....The ADVANCE II study update anticipated in December 2021..."

Commercial • P2 data • Acute Myelogenous Leukemia • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Hepatocellular Cancer • Kidney Cancer • Leukemia • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Squamous Cell Carcinoma of Head and Neck

Immunicum AB (publ) Interim Report April - June 2021 (GlobeNewswire) - "The ADVANCE II study is fully enrolled and on track for an additional read-out in Q4 2021....Immunicum expanded its in-house process development activities to include ilixadencel and initiated in-house research activities for developing next-generation immune primers....Immunicum presented data at the Association of Cancer Immunotherapy (CIMT) and the EHA conferences, supporting the mode of action of its lead programs and providing preclinical validation for potential novel combination therapies. Immunicum broadened the basis for its US patent covering the DCOne® platform and was issued a new US patent covering novel therapies based on the combination of vaccination and intratumoral immune priming."

P2 data • Patent • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Immunicum Announces Positive Review by Data Safety Monitoring Board for Phase Ib Part of ILIAD Study (GlobeNewswire) - "Immunicum...today announced that the independent Data Safety and Monitoring Board (DSMB) for the Phase Ib/II ILIAD study completed its assessment of the Phase Ib part of the ILIAD trial, evaluating the Company’s off-the-shelf, cell-based immune primer ilixadencel in combination with anti-PD1 checkpoint inhibitor Keytruda® (pembrolizumab), in different cancer indications...'We are looking forward to the longer-term results of the Phase Ib part which we expect later this year and will provide further guidance on our clinical development planning before the end of 2021.'"

DSMB • P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

MERECA: Intratumoral Vaccination With Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy vs Sunitinib Post-nephrectomy in Newly Diagnosed Metastatic Renal Cell Carcinoma (mRCC) (clinicaltrials.gov) - P2; N=88; Completed; Sponsor: Immunicum AB; Trial completion date: Aug 2019 ➔ Jan 2021; Trial primary completion date: Aug 2019 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor