CX3CR1

SAN CARLOS, Calif.--(BUSINESS WIRE)-- Two new studies propose the first model for diagnosing, indexing and monitoring Post-Acute Sequelae of COVID-19 (PASC), also known as long COVID or long haul COVID. The findings also provide a framework for understanding the cause of, and potential treatment for, long COVID. Long COVID is believed to affect as many as 30 percent of people who have recovered from initial infection with COVID-19. In the study Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) Up to 15 Months Post-Infection conducted by IncellDx and available at bioRxiv, patients with previous COVID infection and lingering symptoms were found to have a distinct immunologic pro by differentiated proportions of monocyte subsets. In the study, the presence of SARS-CoV-2 S1 protein was investigated in 46 people. T-cell, B-cell, and monocytic subsets were analyzed in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly increased compared with healthy controls. Neither monocyte subset was elevated in cases of severe COVID-19. Additionally, the SARS-CoV-2 protein subunit S1 was present in non-classical monocytes among patients thought to have PASC for up to 16 months following initial infection. Monocytes, a type of white blood cell, are involved in adaptive immunity and are instrumental in attacking viruses and other pathogens. In the study Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning, available in Frontiers in Immunology, 224 individuals, including healthy controls and patients spanning the COVID-19 disease continuum, were assessed using machine learning for severity and chronic symptoms following initial infection. CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF were all significantly elevated in long COVID patients compared to healthy controls (P<0.001), while GM-CSF and CCL4 were in significantly lower levels than healthy controls (P=0.01). Data were analyzed to generate objective disease scores for PASC and severe COVID patients. “In these studies, we used machine learning to determine that long haulers have a distinct immunologic pro a high degree of vascular inflammation, which we were then able to develop into an index for objectively diagnosing and monitoring the progress of PASC patients,” said Bruce Patterson, MD, CEO of IncellDx. “The data also suggests a model for understanding the possible cause of PASC. We found SARS-CoV-2 Spike protein in non-classical monocytes, which we know travel all around the body including through the blood brain barrier, and are mobilized during exercise, which may explain why almost every long hauler has exercise intolerance. These cells are bound by what’s called the fractalkine receptor and CCR5 and patrol and ultimately cause inflammation of the cells lining blood vessels all around the body. By blocking the CCL5/CCR5 pathway and the fractalkine/fractalkine receptor pathways, we may have an approach to treat the cause of PASC rather than the symptoms.” “Taken together, findings from these two studies provide an objective and measurable model for understanding what’s happening and why long COVID patients continue to experience symptoms long after initial COVID infection, and why those symptoms are so diverse and widespread. Together with an objective method to diagnosis and monitor patients, we can assess potential therapeutic targets to reduce the survival of S1-containing non-classical monocytes and the associated vascular inflammation, and we now have a much better roadmap for managing patients and deploying effective treatment paradigms. At IncellDx, we’re working to target these pathways therapeutically. We have filed patents to cover the targeting of the CCL5/CCR5 and fractalkine pathways in PASC,” said Dr. Patterson. About IncellDx IncellDx, Inc., located in San Carlos, California, is a single-cell, multi-omic, molecular diagnostics company dedicated to revolutionizing healthcare, one cell at a time. By combining molecular diagnostics with high throughput cellular analysis, the company's focus is on critical life threatening diseases in the areas of COVID-19, infectious disease and oncology/immuno-oncology, including cervical, head and neck, lung, bladder, breast and prostate cancers.

Press Release 03 May 2021 Immunicum AB Presents Preclinical Data for Ilixadencel and DCP-001 at the 18th Cancer Immunotherapy Annual Meeting Immunicum AB (publ; IMMU.ST) announced today the publication of two abstracts for oral presentations covering preclinical data on its lead programs, ilixadencel and DCP-001, at the 18th Cancer Immunotherapy (CIMT) Annual Meeting, held virtually from Monday, May 10 to Wednesday, May 12, 2021. The accepted abstracts are now available on the conference website. The presentations cover updated preclinical data on the combination of ilixadencel with a checkpoint inhibitor targeting CTLA4 and new preclinical data on the mechanism of action of DCP-001 and its combination with the emerging immunotherapy target CD47. “We value the opportunity to present these new encouraging data that further validate our novel immunotherapy approaches,” said Alex Karlsson-Parra, Chief Scientific Officer at Immunicum. “The data, as published today in the abstracts, supports the potential of combining immune primer ilixadencel with a checkpoint inhibitor, and underscores the important interaction with the patient’s own immune cells through the mechanism of action of DCP-001. Both presentations highlight our leadership in developing novel cell-based therapies against cancer.” The data covered in the ilixadencel abstract published today by the conference extends data from previous preclinical experiments of ilixadencel in combination with an anti-CTLA4 checkpoint inhibitor in a CT26 colon carcinoma animal model, which demonstrated that the combination of ilixadencel and anti-CTLA4 led to complete eradication of tumors in 50-80% of the treated animals. These effects were mainly driven by CD8+ T cells and, in the new data to be presented at CIMT, characterization of CD8+ T cells from blood samples confirmed that the combination of ilixadencel and anti-CTLA4 therapy increased the frequency of CD8+ T cells with the specific markers NKG2D, CX3CR1 and CD39. These markers indicate a crucial population related to tumor-infiltrating cells with a ‘tumor-matched’ phenotype that is able to attack cancer cells. For the abstract covering DCP-001, new preclinical data elucidate the mechanism of action through which DCP-001 can induce specific anti-tumor immunity in patients’ immune cells. The preclinical evaluation of DCP-001 mixed with the host immune cells, called peripheral blood mononuclear cells (PBMCs), shows the induction of the production of various pro-inflammatory cytokines and chemokines by these PBMCs. In addition, DCP-001 was efficiently taken up by immature monocyte-derived dendritic cells, and the blockade of the “don’t eat me” signal and emerging immunotherapy target CD47 enhanced the uptake of DCP-001. These results suggest a vital role for the patient’s immune cells in triggering the immune response upon DCP-001 vaccination and support the clinical rationale for further combination therapies including CD47 inhibitors. Abstracts for the CIMT Annual Meeting were published today in the online program book on the CIMT conference website available via this link. eTalks will be available for registered attendees for on-demand participation at the online conference platform through June 12, 2021. Details on the presentations are as follows: Title:                      Combining intratumoral administration of inflammatory allogeneic DCs with systemic anti-CTLA-4 treatment leads to tumor eradication and is associated with peripheral expansion of CD8+ effector cells with a “tumor-matched” phenotype Abstract #:              A-217 Session Topic:         Therapeutic Vaccination eTalk Session:         eTalk Session 1, Monday, 10 May 2021; 2:00-3:00 pm (CEST) Presenter:                Alex Karlsson-Parra, Chief Scientific Officer at Immunicum Title:                       CD47 and phosphatidylserine contribute to the interaction between antigen presenting cells and the allogeneic cell-based relapse vaccine DCP-001 Abstract #:                A-337 Session Topic:          Cellular Therapy eTalk Session:          eTalk Session 2, Tuesday, 11 May 2021; 5:00-6:00 pm (CEST) Presenter:                 Satwinder Kaur Singh, Director of Research at Immunicum For more information, please contact: Erik Manting Chief Executive Officer Telephone: +31 713 322 627 E-mail: ir@immunicum.com Investor Relations Sijme Zeilemaker Head of Investor Relations & Corporate Communication Telephone: +46 8 732 8400 E-mail: ir@immunicum.com Media Relations Eva Mulder and Sophia Hergenhan Trophic Communications Telephone: +49 175 222 57 56 E-mail: immu@trophic.eu About Immunicum AB (publ) Immunicum is leveraging its unparalleled expertise in dendritic cell biology to develop novel, off-the-shelf, cell-based therapies for solid and blood-borne tumors. With complementary therapeutic approaches in Phase II clinical development that are based on intratumoral priming and cancer relapse vaccination, the company aims to improve survival outcomes and quality of life for a broad population of cancer patients. Based in Sweden and the Netherlands, Immunicum is publicly traded on the Nasdaq Stockholm. Attachment

Press Release 03 May 2021 Immunicum AB Presents Preclinical Data for Ilixadencel and DCP-001 at the 18th Cancer Immunotherapy Annual Meeting Immunicum AB (publ; IMMU.ST) announced today the publication of two abstracts for oral presentations covering preclinical data on its lead programs, ilixadencel and DCP-001, at the 18th Cancer Immunotherapy (CIMT) Annual Meeting, held virtually from Monday, May 10 to Wednesday, May 12, 2021. The accepted abstracts are now available on the conference website. The presentations cover updated preclinical data on the combination of ilixadencel with a checkpoint inhibitor targeting CTLA4 and new preclinical data on the mechanism of action of DCP-001 and its combination with the emerging immunotherapy target CD47. “We value the opportunity to present these new encouraging data that further validate our novel immunotherapy approaches,” said Alex Karlsson-Parra, Chief Scientific Officer at Immunicum. “The data, as published today in the abstracts, supports the potential of combining immune primer ilixadencel with a checkpoint inhibitor, and underscores the important interaction with the patient’s own immune cells through the mechanism of action of DCP-001. Both presentations highlight our leadership in developing novel cell-based therapies against cancer.” The data covered in the ilixadencel abstract published today by the conference extends data from previous preclinical experiments of ilixadencel in combination with an anti-CTLA4 checkpoint inhibitor in a CT26 colon carcinoma animal model, which demonstrated that the combination of ilixadencel and anti-CTLA4 led to complete eradication of tumors in 50-80% of the treated animals. These effects were mainly driven by CD8+ T cells and, in the new data to be presented at CIMT, characterization of CD8+ T cells from blood samples confirmed that the combination of ilixadencel and anti-CTLA4 therapy increased the frequency of CD8+ T cells with the specific markers NKG2D, CX3CR1 and CD39. These markers indicate a crucial population related to tumor-infiltrating cells with a ‘tumor-matched’ phenotype that is able to attack cancer cells. For the abstract covering DCP-001, new preclinical data elucidate the mechanism of action through which DCP-001 can induce specific anti-tumor immunity in patients’ immune cells. The preclinical evaluation of DCP-001 mixed with the host immune cells, called peripheral blood mononuclear cells (PBMCs), shows the induction of the production of various pro-inflammatory cytokines and chemokines by these PBMCs. In addition, DCP-001 was efficiently taken up by immature monocyte-derived dendritic cells, and the blockade of the “don’t eat me” signal and emerging immunotherapy target CD47 enhanced the uptake of DCP-001. These results suggest a vital role for the patient’s immune cells in triggering the immune response upon DCP-001 vaccination and support the clinical rationale for further combination therapies including CD47 inhibitors. Abstracts for the CIMT Annual Meeting were published today in the online program book on the CIMT conference website available via this link. eTalks will be available for registered attendees for on-demand participation at the online conference platform through June 12, 2021. Details on the presentations are as follows: Title:                      Combining intratumoral administration of inflammatory allogeneic DCs with systemic anti-CTLA-4 treatment leads to tumor eradication and is associated with peripheral expansion of CD8+ effector cells with a “tumor-matched” phenotype Abstract #:              A-217 Session Topic:         Therapeutic Vaccination eTalk Session:         eTalk Session 1, Monday, 10 May 2021; 2:00-3:00 pm (CEST) Presenter:                Alex Karlsson-Parra, Chief Scientific Officer at Immunicum Title:                       CD47 and phosphatidylserine contribute to the interaction between antigen presenting cells and the allogeneic cell-based relapse vaccine DCP-001 Abstract #:                A-337 Session Topic:          Cellular Therapy eTalk Session:          eTalk Session 2, Tuesday, 11 May 2021; 5:00-6:00 pm (CEST) Presenter:                 Satwinder Kaur Singh, Director of Research at Immunicum For more information, please contact: Erik Manting Chief Executive Officer Telephone: +31 713 322 627 E-mail: ir@immunicum.com Investor Relations Sijme Zeilemaker Head of Investor Relations & Corporate Communication Telephone: +46 8 732 8400 E-mail: ir@immunicum.com Media Relations Eva Mulder and Sophia Hergenhan Trophic Communications Telephone: +49 175 222 57 56 E-mail: immu@trophic.eu About Immunicum AB (publ) Immunicum is leveraging its unparalleled expertise in dendritic cell biology to develop novel, off-the-shelf, cell-based therapies for solid and blood-borne tumors. With complementary therapeutic approaches in Phase II clinical development that are based on intratumoral priming and cancer relapse vaccination, the company aims to improve survival outcomes and quality of life for a broad population of cancer patients. Based in Sweden and the Netherlands, Immunicum is publicly traded on the Nasdaq Stockholm. Attachment