Pipeline Overview

OncoImmune’s founders have identified a novel pathway that is a checkpoint for the development of a number of disease indications. Our lead molecule, CD24Fc, targets this pathway and efficiently suppresses the immune response in animal models of GVHD, multiple sclerosis and rheumatoid arthritis. Furthermore, we have demonstrated the importance of this inhibitory pathway in sepsis and shown that bacterial sialidases exacerbate inflammation in mouse models. Accordingly, we are developing novel sialidase inhibitors for the treatment of polybacterial sepsis.

In addition to our in-house flagship program on CD24Fc, OncoImmune is developing a host of unique technologies developed by its founders. Pipeline products based on these technologies are in development for the treatment of cancer and autoimmune disease.

  • Discovery
  • Pre-Clinical
  • Phase 1
  • Phase 2
  • Phase 3
Sialidase inhibitors (Sepsis)
Onc-392 (Oncology)
Echinomycin (AML)


OncoImmune’s lead compound is CD24Fc, a first-in-class recombinant fusion protein that targets a novel immune pathway checkpoint.  CD24Fc has demonstrated efficacy in animal models of GVHD, multiple sclerosis and rheumatoid arthritis, and safety in a Phase I trial in healthy human subjects. We are currently preparing for a Phase II study for the prophylactic treatment of graft-versus-host disease (GVHD).

Pattern recognition receptors, such as Toll or Toll-like receptors (TLRs), recognize pathogens (Pathogen-Associated Molecular Patterns, or PAMPs) or components of injured cells (Danger-Associated Molecular Patterns, or DAMPs), and trigger activation of the innate immune system. On the other hand, Siglec is a distinct class of pattern recognition receptor that down-regulates cellular response. As reported by our founders in Science (2009) and Nature Biotech (2011), CD24 interacts with DAMPs as well as a pattern recognition receptor, which is called Siglec G in mice and Siglec 10 in human, to selectively regulate host response to DAMPs.

Specifically, CD24-Siglec-G (or its human homologue, Siglec 10) interaction negatively regulates the activity of NFkB via intracellular ITIM domains that are associated with SHP-1. Accordingly, binding of CD24 to Siglec G/10 suppresses TNF-α, IL-1β and IL-6, which are all major targets of autoimmune diseases and cancer. Furthermore, CD24 binds to several DAMPs and represses host response to these DAMPs.

Therefore, CD24Fc has a dual mechanism of action:

  • First, CD24Fc binds DAMPs, trapping the inflammatory stimuli to prevent their interaction with TLR receptors
  • Second, CD24Fc binds Siglec G/10 and regulates host response to tissue injuries through Siglec G/10-associated SHP1 inhibitory signaling

Both mechanisms likely act in concert as mice with targeted mutation of either CD24 or Siglec G mount much stronger inflammatory response.

Endogenous CD24 Inhibits Inflammatory Responses

CD24Fc Mimics/Augments Endogenous CD24 Activity

Graft-versus-host disease (GVHD) is a life threatening condition that occurs when the immune competent cells in a tissue graft mount an immune attack against the host. GVHD is most commonly associated with hematopoietic stem cell transplantation (HSCT) for the treatment of hematologic malignancies. Activated donor T cells damage host epithelial cells following an inflammatory cascade that begins with the preparative myeloablative regimen.

Host tissue injuries caused by HSCT conditioning regimens, including high-dose chemotherapy and/or total body irradiation (TBI), is considered to be the first step in the development of acute GVHD. Host tissue injuries caused by the conditioning regimen lead to the release of proinflammatory cytokines, such as TNF-α, IL-1β and IL-6, and also the release of DAMPs and PAMPs. Both DAMPs and PAMPs can activate antigen-presenting cells (APCs), such as dendritic cells (DCs), which are critical for the activation of the donor T cells and the development of acute GVHD.

Our founders we have established that CD24-Siglec G axis regulates the severity of GVHD and that CD24Fc prevents GVHD in animal models of GVHD by interacting with Siglec G. Importantly, CD24Fc does not suppress PAMP-mediated or antigen-specific immune responses, which suggests that CD24Fc will not increase the risk of infection, a major limitation of other approaches such as T cell depletion. Furthermore, CD24Fc prevents GVHD but preserves GVL, making it an ideal drug for prophylaxis of GVHD in leukemia patients.

OncoImmune has received orphan drug designation for CD24Fc in both the US and Europe and we are currently preparing for a Phase II study the use of CD24Fc in the prophylactic treatment of graft-versus-host disease (GVHD).

Beyond GVHD, genetic analysis of a variety of autoimmune disease in human, including multiple sclerosis, systemic lupus erythromatosus, rheumatoid arthritis, and giant cell arthritis, showed significant association between CD24 polymorphism and risk of autoimmune diseases. In mice, CD24Fc reduces the production of multiple cytokines involved in the pathogenesis of RA and is highly effective in treating disease in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.

Sialidase Inhibitors

OncoImmune’s founders have demonstrated that the CD24-Siglec G/10 axis also regulates the inflammation associated with sepsis, and that bacterial sialidases can exacerbate the inflammatory responses by desiylating CD24 and preventing its interaction with Siglec G/10. OncoImmune is developing proprietary sialidase inhibitors as a new therapeutic strategy for the prevention of Sepsis.

Sepsis is a potentially life-threatening complication triggered by infection, most commonly by bacteria. Sepsis occurs when chemicals released into the bloodstream to fight the infection trigger inflammatory responses throughout the whole body. In turn, this inflammation can trigger a cascade of events that can damage multiple organs, causing them to fail.

Recognition of Pathogen-Associated Molecular Patterns (PAMPs) by Toll-like receptors (TLRs) and NOD-like receptors (NLRs) initiates an inflammatory immune response that plays a critical role in protecting host against infection. In addition, TLRs and NLRs also recognize Damage-Associated Molecular Patterns (DAMPs) to initiate limited innate immune responses. However, while innate immune response to DAMPs may be important for tissue repair and wound healing, it is normally well controlled to avoid autoimmune tissue destruction.

The CD24-Siglec G/10 pathway is critical in discriminating DAMP from PAMP mediated inflammation by selectively repressing host responses to DAMPs. CD24 is a heavily glycosylated glycoprotein and binds to Siglecs (Sialic acid-binding immunoglobulin-type lectins) through its sialic acid-containing structures. This sialoside-based pattern recognition discriminates infections from aseptic tissue injuries through a trimolecular complex of CD24, DAMPs and Siglec G/10 that inhibits the activation of TLRs and NLRs.

During infection, pathogen-encoded sialidases prevent CD24 from interacting with Siglec G/10 and, as a result, DAMPs and PAMPs become indistinguishable and inflammatory response are exacerbated. However, blocking sialidase activity with small-molecule inhibitors leads to a substantial reduction of the inflammatory response and subsequent morbidity in mouse models of Sepsis. OncoImmune is currently developing novel sialidase inhibitors for the treatment of Sepsis.


In many cancers, disease progression is associated by the expression of immune suppressive molecules or immune suppressive cells in tumor microenvironment that interfere with an effective antitumor response. However, recent advances in the field of immuno-oncology have demonstrated the ability to overcome cancer-mediated suppression and harness the natural power of the immune system to combat disease.

Despite reduced toxicity to normal tissue as seen with classical chemotherapy, significant autoimmune side-effects have been observed in clinical trials with immune-stimulating monoclonal antibodies. In some cases, this is the result of preclinical screening of lead molecules because in vitro immunological correlates are sometimes of little value in predicting in vivo activity.

OncoImmune is overcoming this limitation by using proprietary in vivo screening models for drug selection and we are currently developing a novel monoclonal antibody that demonstrated reduced immune related toxicities while retaining potent anti-tumor immunity.


Echinomycin has been used unsuccessfully in the treatment of solid tumors but not previously evaluated in the patients with haematological malignancies. OncoImmune’s founders have demonstrated that echinomycin is highly effective at selectively targeting leukemia stem cells (LSCs) and we are developing novel formulations of Echinomycin for the treatment of Acute myeloid leukemia (AML). 

AML is a fast-growing form of cancer of the blood and bone marrow, and the most common type of acute leukemia. Treatment of AML is usually divided into 2 chemotherapy (chemo) phases: Remission Induction which is aimed at getting rid of as many leukemia cells as possible, and Consolidation (post-remission therapy) which aims to destroy any remaining leukemia cells and prevent a relapse. However, while current therapy can result in complete remission (CR) in the majority of AML cases, relapsed AML (rAML) occurs in >50% patients within two years of CR. Among them, more than 60% succumb to AML within two years of relapse and is generally resistant to chemotherapy. Recent studies suggest that leukemia stem cells (LSC) are highly resistant to conventional chemotherapy and thus likely responsible for relapse. Therefore, therapeutic elimination of LSC may offer a new strategy for the treatment of rAML.

Echinomycin is a DNA intercalating cyclic peptide which belongs to a member of quinoxaline antibiotics originally isolated from Streptomyces echinatus. Because of its anti-neoplastic activities against murine tumors, echinomycin was brought into clinical development for solid tumors by the National Cancer Institute (NCI) in multiple phase I and phase II studies. However, the dose-limiting toxicity (DLT) in all trials, regardless of schedule, was severe and often protracted and echinomycin was not consistently effective for adult patients with solid tumors. Accordingly, clinical development of echinomycin was discontinued.

Using a transgenic mouse model of lymphoma/leukemia, OncoImmune’s founders identified a subset of cells with stem cell like self renewing properties. This cell population was found to be particularly susceptible to the HIF-1a inhibitor, echinomycin, whereas inhibitors of other pathways had little to no effect on cell viability. Furthermore, the lymphoma CSCs were approximately 100-fold more sensitive than normal hematopoeitic progenitor cells (HPCs) and echinomycin treatment results in long-lasting elimination of lymphoma CSCs as demonstrated by a complete lack of recurrence in treated mice. The HIF-1a -Notch pathway was determined to be essential for the maintenance of these cancer stem cells (CSCs) in hematological malignancies under normoxia.

Leukemia stem cells (LSCs) from AML display a similar increase in HIF-1a expression. The inhibitory effect of echinomycin was demonstrated in 7 independent primary AML samples taken from the bone marrow (BM) or peripheral blood (PB). In the xenogeneic model of human AML, short-term treatment by echinomycin prevented serial transplantation of AML, supporting the use of echinomycin as a therapeutic agent for AML.

The major limitation of echinomycin as a drug product, is the narrow therapeutic window due to its short half life. OncoImmune is developing new formulations of echinomycin with increased half life and we have received orphan drug designation from the FDA for the treatment of AML.

© Copyright - OncoImmune