Rubius Therapeutics

Founded by Flagship Pioneering in 2014, Rubius Therapeutics (NASDAQ: RUBY) is a clinical-stage biopharmaceutical company pioneering a new era of cellular medicines. The company’s proprietary RED PLATFORM^® was designed to genetically engineer and culture Red Cell Therapeutics™ (RCTs™) that are selective, potent, and off-the-shelf allogeneic cellular therapies for the potential treatment of diseases across multiple therapeutic areas.

Rubius’ initial focus is to advance RCT product candidates for the treatment of cancer and autoimmune diseases by leveraging two distinct therapeutic modalities: potent cell-cell interaction and tolerance induction.

Rubius’ lead oncology product candidate, RTX-240, is an allogeneic cellular therapy being evaluated in two Phase 1 clinical trials for the treatment of patients with relapsed/refractory or locally advanced solid tumors and relapsed/refractory acute myeloid leukemia. Additionally, Rubius plans to file an IND for RTX-321 for the treatment of human papillomavirus–positive tumors by year end 2020.

Cancer

Recent advances in cancer treatment have focused on activating the immune system. Despite progress, existing immunotherapies are effective in a relatively small number of patients and types of cancer. Furthermore, even when therapies are initially effective, eventually the disease ceases to respond to treatment and progresses.

RCT product candidates can be engineered to express combinations of costimulatory molecules and cytokines on their cell surface to directly engage both the adaptive immune system and the innate immune system. By stimulating both powerful arms of the immune system, RCTs may be better able to destroy cancer cells to improve anti-tumor activity and overcome resistance to immunotherapy.

RTX-240

RTX-240 is an allogeneic cellular therapy product candidate that simultaneously presents hundreds of thousands of copies of the costimulatory 4-1BB ligand (4-1BBL) and the trans-presented cytokine interleukin-15 (IL-15TP) in their native forms to activate and expand natural killer and T cells. 4-1BBL is a costimulatory molecule that can drive T and NK cell proliferation and activation and interferon gamma production. IL-15 is a cytokine that bridges innate and adaptive immunity by promoting NK and T cell proliferation and NK cell cytotoxicity. IL-15TP is a fusion of IL-15 and IL-15 receptor alpha. RTX-240 has the potential to enable the following benefits:

• Activate existing agonist pathways leading to enhanced potency

• Improve anti-tumor activity

• Overcome resistance to immunotherapy

• Reduce toxicity given biodistribution

RTX-240 is being evaluated in two Phase 1 clinical trials for the treatment of patients with relapsed/refractory or locally advanced solid tumors and in relapsed/refractory acute myeloid leukemia.

RTX-321

RTX-321 is an investigational allogeneic artificial antigen-presenting cell, or aAPC, therapy that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells and promoting cytokine production and cytolytic activity, which could result in killing tumor cells. RTX-321 expresses a human papillomavirus (HPV) peptide antigen bound to major histocompatibility complex class I proteins, 4-1BBL (a costimulatory signal) and IL-12 (a cytokine) on the cell surface to mimic human T cell–APC interactions.

Rubius plans to file an IND for RTX-321 for the treatment of HPV-positive tumors by year end 2020.

Autoimmune Diseases

Rubius can engineer cells to express specific autoimmune disease–associated antigens either within the cell or on its surface to take advantage of how the body normally maintains self-tolerance, thereby retraining the immune system to cease seeing self-antigens as foreign.

In addition, the company can express immune-modulating cytokines, enzymes, and inhibitory immune signals, which may have the potential to enhance the tolerogenic effects of Red Cell Therapeutics.

RCTs have the potential to more specifically modulate complex counterregulatory immune responses and enable greater efficacy with lower toxicity, potentially providing treatment options for a number of autoimmune diseases and, in some cases, even cures.

Rubius has a preclinical autoimmune program in Type 1 diabetes.