Rubius Therapeutics Announces Extensive Preclinical Data for Three Red Cell Therapeutic Oncology Programs at the 2019 American Association for Cancer Research Annual Meeting
RCT™ oncology product candidates are engineered to express combinations of co-stimulatory molecules and cytokines on the cell surface in their natural conformation that directly engage T and NK cells to activate the adaptive and innate immune systems through direct cell-cell interaction, replicating how the immune system naturally functions, to attack and kill tumors. Additionally, and in contrast to adoptive or autologous cell therapy approaches that require engineering a patient’s own T cells,
RTX-240 (4-1BBL and IL-15TP) Red Cell Therapeutic Product Candidate
- RTX-240 is an allogeneic cellular therapy product candidate engineered to replicate the human immune system by stimulating the adaptive and innate immune systems to generate an immune response.
- RTX-240 simultaneously presents hundreds of thousands of copies of 4-1BB ligand (4-1BBL) and IL15TP, a fusion of IL-15 and IL-15 receptor alpha, in their native forms to activate and expand T and NK cells for the potential treatment of solid tumors.
- In the results presented today, RTX-240 demonstrated a potentially wide therapeutic window with potent immune stimulation, antitumor activity and no observed toxicity.
- 4-1BBL and IL-15TP demonstrated synergistic and complementary effects in promoting innate and adaptive immunity:
○ RTX-240’s cellular presentation of the native conformation of 4-1BBL led to more potent activation - 10-fold higher activation - of the 4-1BB pathway compared to a 4-1BB agonist antibody in vitro.
○ A murine surrogate for RTX-240, called mRBC-240, promoted significant expansion and activation of key cells driving innate and adaptive immune responses in vivo, including activation and proliferation of CD8 T cells and NK cells.
○ mRBC-240 demonstrated potent antitumor activity by significantly reducing the number of lung metastases and increasing the number of NK cells in the lung, including terminally differentiated NK cells, compared to control mice in a B16F10 mouse model.
- mRBC-240 resulted in no observed liver toxicity in vivo, likely due its restriction to the vasculature.
- Rubius plans to file an Investigational New Drug application for RTX-240 by early 2020.
RTX-224 (4-1BBL and IL-12) Red Cell Therapeutic Product Candidate
- RTX-224 is an allogeneic cellular therapy product candidate engineered to replicate the human immune system by stimulating the adaptive and innate immune systems to generate an immune response.
- RTX-224 simultaneously presents hundreds of thousands of copies of 4-1BBL in its native form and IL-12 on the cell surface to activate T and NK cells for the potential treatment of solid tumors.
- In the results presented today, RTX-224 demonstrated a potentially wide therapeutic window with highly potent antitumor activity and no observed toxicity in murine models.
- RTX-224 promoted significant expansion and activation of key cells driving innate and adaptive immune responses in vivo, including NK cell proliferation, NK cell cytotoxic activity, stimulation of IFNγ production and proliferation of CD4- and CD8-positive T cells.
- A murine surrogate for RTX-224, called mRBC-224, demonstrated significant tumor growth inhibition in both a lung metastasis and subcutaneous B16F10 mouse model, and, when combined with anti-PD-1 antibody, demonstrated significant tumor shrinkage in the MC38 colon cancer mouse model.
- In contrast to systemic treatment with recombinant IL-12, mRBC-224 also resulted in no observed organ toxicity in vivo, likely due to its restriction to the vasculature.
- RTX-224 is the second most advanced oncology product candidate within the
Red Cell Therapeutic Artificial Antigen-Presenting Cell (aAPC)
- RCT artificial antigen presenting cells (RTX-aAPCs) are engineered to induce a tumor-specific response by expanding tumor-specific T cells against a target antigen.
- Rubius Therapeutics’ first aAPC product candidate is for the potential treatment of HPV-positive cancers.
- RTX-aAPC (HPV+) is engineered to express on the cell surface an HPV peptide antigen on the major histocompatibility complex (MHC) I, a costimulatory signal, and a cytokine to recapitulate the human immunobiology of T cell-APC interactions.
- In the results presented today, RTX-aAPCs activate and significantly expand antigen-specific T cells in vitro and in vivo, reduce tumor burden and have no observed toxicity in murine models.
○ RTX-aAPC (HPV+) selectively activated antigen-specific T cells directed against a dominant epitope in HPV-positive cancers.
- Additionally, to demonstrate preclinical proof-of-concept, a murine surrogate aAPC, called mRBC-aAPC (OVA), was engineered to express an OVA peptide antigen on MHC I and the costimulatory molecule 4-1BBL.
- mRBC-aAPC (OVA) dramatically increased expansion of OVA-specific T cells 60-fold higher in the spleen and 30-fold higher in the lymph nodes compared to controls in vivo.
- mRBC-aAPC (OVA) also promoted substantial tumor regressions in an OVA-positive murine model leading to extended survival.
- mRBC-aAPC (OVA) treatment resulted in no body weight changes and no observed liver toxicity.
- These data suggest that antigen‑specific T cells are expanded in the vasculature and spleen and subsequently traffic to the tumor.
- Rubius Therapeutics’ RTX-aAPC platform is a modular and versatile immunotherapy platform that is designed to target antigen‑specific T cells across multiple tumor types using common antigens or neoantigens.
About Rubius Therapeutics Oncology Approach
RCT product candidates can be engineered to express combinations of co-stimulatory molecules and cytokines on the cell surface in their natural conformation to directly engage T and NK cells to activate the adaptive and innate immune systems. The goal is to stimulate these immune cells to proliferate, activate, migrate and, ultimately, to attack and kill tumors. Rubius Therapeutics’ lead oncology candidates each are designed to stimulate the immune system in different ways and provide several benefits over existing immuno-oncology approaches: 1) the expression of natural ligands in the appropriate conformation and in synergistic combinations is expected to provide a more potent activation of the immune system; 2) RCTs are confined to the vasculature versus administered systemically, which is expected to result in an improved safety profile; and 3) as a result, RCTs are expected to have a broader therapeutic window.
Additionally, and in contrast to adoptive or autologous cell therapy approaches that require engineering a patient’s own T cells,
About Rubius Therapeutics
Rubius Therapeutics is a clinical-stage biopharmaceutical company developing a new class of medicines called Red Cell Therapeutics™. The Company’s proprietary RED PLATFORM® was designed to genetically engineer and culture Red Cell Therapeutics™ that are selective, potent and off-the-shelf allogeneic cellular therapies for the potential treatment of several diseases across multiple therapeutic areas. Rubius’ initial focus is to advance RCT™ product candidates for the treatment of rare diseases, cancer and autoimmune diseases by leveraging three distinct therapeutic modalities — cellular shielding, potent cell-cell interaction and tolerance induction. For more information, visit www.rubiustx.com or follow us on Twitter and LinkedIn.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding our expectations regarding the therapeutic potential of our RCTs, the expected timing and progress of our RCT product candidates, the timeline for us to file an IND for RTX-240, and our strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “goal,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the development of our RCT product candidates and their therapeutic potential and other risks identified in our
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Source: Rubius Therapeutics