Respiratory Viral Diseases

DAS181 is a first-in-class host-directed recombinant sialidase protein derived from actinomyces viscosus (av).  It was designed to remove sialic acids located on the surface of epithelial cells lining the human respiratory tract.  These sialic acids are naturally present on cell surfaces and are needed by many viruses, including influenza, parainfluenza, metapneumovirus, and enterovirus68, for entry into cells. Cleavage of sialic acid on the patient’s respiratory epithelial cells may block viral entry, and provide a host-directed mechanism to treat respiratory viral infections.

Ongoing Clinical Trials for DAS181
DAS181 Biology

Solid Tumors

Multi-modality anti-solid tumor platforms

  • Innovative therapies are required for solid tumors due to the high incidence and mortality rates they cause for cancer patients.  This is especially true for tumors without driver oncogenes or tumors without a high mutational burden because these tumors do not respond to traditional targeted therapies and immune checkpoint inhibitors.
  • Malignant tumors have developed multiple mechanisms, such as hyper sialylation, downregulation of MHC and upregulation of immune checkpoints to evade immune surveillance.  Also, the adaptive immune system becomes progressively ineffective, as manifested by exhausted cytotoxic T cells, dysfunctional NK cells and immunosuppressive tumor-associated myeloid cells.
  • To effectively prevent immune escape and restore tumor surveillance, Ansun’s approach is to target both tumor and immune cells, at different checkpoints from innate to adaptive immunity using different therapeutic modalities.
Multi-modality anti-solid tumor platforms

Allogeneic CAR-NK/γδ-T cell therapy

  • Natural killer (NK) cells and γδ T cells are cytotoxic lymphocytes that straddle the interface of innate and adaptive immunity. They both recognize a broad range of tumor, viral, and foreign antigens without the presentation by MHC, which is often down regulated in solid tumors. They can kill target cells directly (through the release of perforin and granzyme B), or indirectly through antibody-dependent cellular cytotoxicity (ADCC) and secretion of inflammatory cytokines.
  • Ansun’s proprietary CAR-NK is derived from healthy donor peripheral blood using a feeder-cell free process that has the flexibility to expand either NK and/or γδ T cells at scale.
  • Our donor-derived NK cell product has a diverse repertoire of licensed and educated NK cells, which are superior effectors with increased cytotoxic capacity against “missing-self” tumors. The anti-tumor activity can be further enhanced in CAR-NK expressing chimeric antigen receptors.
Read More

avSialidase-armed oncolytic vaccinia virus (avSial-VV)

  • Vaccinia virus has unique advantages in treating cold tumors. Its rapid lytic replication in tumor cells results in release of tumor antigens and danger signals that activate host immune responses. VV has been shown to be safe and well tolerated in patients, and has broad tissue tropism and large cargo capacity for transgene incorporation.
  • Ansun’s proprietary avSialidase-armed VV is designed to target tumor cells with abnormal sialylation, which is a major mechanism for immune evasion and tumor metastasis. The local delivery of avSial-VV minimizes the potential on-target off-tumor activity of sialidase, while potently removing the glyco-immune checkpoint for activation of infiltrating immune cells. The activity can be further enhanced by incorporation of additional tumor targeting transgenes.
  • In combination with avSialidase CAR-NK, the membrane bound avSialidase expressed by avSial-VV in infected tumor cells can also serve as a universal tumor target for a broad range of solid tumors.

TME-modulating antibodies

  • The suppressive tumor microenvironment (TME) is a key challenge in treating solid tumors. The presence of tumor-associated macrophages (TAM), myeloid-derived suppressive cells (MDSC) and Treg cells in the TME inhibit the activation of lymphocytes and induce T cell exhaustion and NK dysfunction.
  • LILRB2 is a master negative regulator on myeloid cells. The LILRB2-41BB bsAb aims to convert the protumor M2 to antitumor M1 macrophage, promote DC activation, antigen presentation and activation of endogenous T cells.
  • Ansun’s proprietary bispecific Ab to leukocyte immunoglobulin-like receptor B2 (LILRB2) and 41BB can augment the anti-tumor activities of the endogenous immune cells as well as immunotherapies such as avSial-VV or CAR-NK.

Multi-modality combination immunotherapies

Oncolytic Virus

Combo Therapies Illustration - 1

CAR-NK/γδ-T

Combo Therapies Illustration - 2

Biologics

Combo Therapies Illustration - 3

Ansun’s multi-modality combination approach aims to provide the most efficient and robust pan-tumor solution

Multi-Modality Immune Oncology Toolset
Multi-Modality Immune Oncology Toolset - legend