ADVANCING A BROAD AND DIVERSE PIPELINE

Rubius Therapeutics is advancing a broad pipeline of RCT™ product candidates. Our current programs are investigating applications across multiple therapeutic areas—starting with cancer and autoimmune diseases. We are currently enrolling patients in a Phase 1/2 clinical trial of RTX-240; the trial has three separate Phase 1 arms: an ongoing monotherapy dose escalation arm in adults with relapsed/refractory or locally advanced solid tumors, an ongoing monotherapy dose escalation arm in adults with relapsed/refractory acute myeloid leukemia, and a combination therapy dose escalation arm with pembrolizumab in adults with relapsed/refractory or locally advanced solid tumors. We are also enrolling patients in a Phase 1 clinical trial of RTX-321 for the treatment of human papillomavirus 16-positive cancers. Additionally, Rubius plans to file an IND for RTX-224 for the treatment of solid tumors by year-end 2021.

Candidate
Preclinical
IND Enabling
Phase 1
Phase 2
Phase 3

Cancer

R/R Solid Tumors

RTX-240, Rubius Therapeutics’ lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both natural killer (NK) and memory T cells to generate a potent anti-tumor response.

Trial Information

R/R Solid tumors

RTX-240, Rubius Therapeutics’ lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both natural killer (NK) and memory T cells to generate a potent anti-tumor response.

#rtx-240-monotherapy
R/R Acute Myeloid Leukemia

RTX-240, Rubius Therapeutics' lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to induce natural killer (NK) and T cell activation and proliferation, leading to the killing of AML cells.

Trial Information

R/R Acute Myeloid Leukemia
PreClinical

RTX-240, Rubius Therapeutics' lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to induce natural killer (NK) and T cell activation and proliferation, leading to the killing of AML cells.

#aml
RTX-240 + pembrolizumab – R/R Solid Tumors

RTX-240 is engineered to express a co-stimulatory molecule, 4-1BB ligand, and a cytokine, IL-15TP, on the cell’s surface, and is designed to broadly stimulate the immune system by activating and expanding both natural killer (NK) cells and T cells to generate a potent anti-tumor response. The goal of the Phase 1 combination arm with KEYTRUDA® (pembrolizumab)1 is to provide benefit to patients with cancers that have relapsed or are refractory after treatment with anti-PD-1 or PD-L1 antibodies.

Trial Information

  1. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
RTX-240 + pembrolizumab – R/R Solid Tumors

RTX-240 is engineered to express a co-stimulatory molecule, 4-1BB ligand, and a cytokine, IL-15TP, on the cell’s surface, and is designed to broadly stimulate the immune system by activating and expanding both natural killer (NK) cells and T cells to generate a potent anti-tumor response. The goal of the Phase 1 combination arm with KEYTRUDA® (pembrolizumab)1 is to provide benefit to patients with cancers that have relapsed or are refractory after treatment with anti-PD-1 or PD-L1 antibodies.

#rtx-240-combination
  1. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
R/R HPV 16+ Solid Tumors

RTX-321 is an allogeneic, off-the-shelf artificial antigen presenting cell (aAPC) therapy product candidate that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells. RTX-321 expresses hundreds of thousands of copies of an HPV peptide antigen bound to major histocompatibility complex (MHC) class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.

Trial Information

R/R HPV 16+ Solid Tumors

RTX-321 is an allogeneic, off-the-shelf artificial antigen presenting cell (aAPC) therapy product candidate that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells. RTX-321 expresses hundreds of thousands of copies of an HPV peptide antigen bound to major histocompatibility complex (MHC) class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.

#hpv
R/R Solid Tumors

RTX-224 is an allogeneic cellular therapy that is engineered to express hundreds of thousands of copies of 4-1BBL and IL-12 on the cell surface. In contrast to RTX-240, RTX-224 is designed as a broad immune agonist of both adaptive and innate responses, activating CD8+ and CD4+ T cells, promoting antigen presentation and retaining the ability to activate and expand NK cells. It is expected to produce a broad and potent anti-tumor T cell response, an innate immune response and have anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and prior activity of checkpoint inhibitors.

R/R Solid Tumors
PreClinical

RTX-224 is an allogeneic cellular therapy that is engineered to express hundreds of thousands of copies of 4-1BBL and IL-12 on the cell surface. In contrast to RTX-240, RTX-224 is designed as a broad immune agonist of both adaptive and innate responses, activating CD8+ and CD4+ T cells, promoting antigen presentation and retaining the ability to activate and expand NK cells. It is expected to produce a broad and potent anti-tumor T cell response, an innate immune response and have anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and prior activity of checkpoint inhibitors.

RTX-aAPC
Cancer

RTX-aAPC
Cancer

Candidate
Preclinical
IND Enabling
Phase 1
Phase 2
Phase 3

Autoimmune Diseases

RTX-T1D
Type 1 Diabetes

RTX-T1D
Type 1 Diabetes
PreClinical

THERAPEUTIC
AREAS

DESIGNED TO ACTIVATE BOTH ARMS OF THE IMMUNE SYSTEM TO STOP CANCER

Recent treatment advances have focused on activating the immune system against cancer. Despite this progress, existing immunotherapies are effective in a relatively small number of patients and types of cancer. Furthermore, even when therapies are initially effective, the disease eventually no longer responds to treatment and progresses.

RCTTM product candidates can be engineered to express combinations of co-stimulatory 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.

We believe RCTs will have broad therapeutic application across a range of both solid tumors and hematological cancers.

AIMING TO RETRAIN THE IMMUNE SYSTEM
TO DEFEAT AUTOIMMUNE DISEASES

Autoimmune diseases are the result of a hyperactive immune response that mistakes healthy tissue as foreign. Over time, these attacks on healthy cells lead to disease. Current therapies are generally administered on a lifelong basis, initially work for only a subset of patients, tend to lose effectiveness over time and are often associated with serious side effects, including opportunistic infections, lymphoma and, in some cases, severe or fatal reactions.

RCTs can be engineered to express disease-causing antigens on their cell surface. When these RCTs are processed by the reticuloendothelial system, these antigens are expected to be presented to the immune system and thereby retrain the body to no longer see these self-antigens as foreign. The resulting restoration or induction of immune tolerance may lead to more effective treatments—potentially even cures—for certain autoimmune diseases, such as Type I diabetes.

RTX-240 for the Treatment of Advanced Solid Tumors

Study Title
Open label, multicenter, multidose, first-in-human Phase 1/2 study of RTX-240 for the treatment of patients with relapsed/refractory or locally advanced solid tumors
Status

Enrolling

Key Objectives
  1. Safety Assessment
  2. Pharmacodynamics of RTX-240 will be evaluated through changes in natural killer and T cell numbers relative to baseline
  3. Anti-tumor activity of RTX-240 measured by Overall Response Rate, or ORR

If you are a patient or a loved one interested in learning more about RTX-240 for the treatment of cancer or participating in a clinical trial, please visit:

RTX-240 + Pembrolizumab for the Treatment of Advanced Solid Tumors

Study Title
Open label, multicenter, multidose, first-in-human Phase 1 study of RTX-240 in combination with pembrolizumab for the treatment of advanced solid tumors
Status

Enrolling

Key Objectives
  1. Safety Assessment
  2. Evaluate the pharmacology of RTX-240 administered in combination with the standard dose of pembrolizumab
  3. Determine the recommended Phase 2 dose of the combination

If you are a patient or a loved one interested in learning more about RTX-240 for the treatment of cancer or participating in a clinical trial, please visit:

RTX-240 for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Study Title
Open label, multicenter, multidose, first-in-human Phase 1 study of RTX-240 for the treatment of patients with relapsed or refractory acute myeloid leukemia
Status

Enrolling

Key Objectives
  1. Safety Assessment
  2. Pharmacodynamics of RTX-240 will be evaluated through changes in natural killer and T cell numbers relative to baseline
  3. Anti-tumor activity of RTX-240 measured by Overall Response Rate, or ORR

If you are a patient or a loved one interested in learning more about RTX-240 for the treatment of cancer or participating in a clinical trial, please visit:

RTX-321 for the Treatment of HPV 16-Positive Cancers

Study Title
Open-label, multicenter, multiple-ascending dose, first-in-human, Phase 1 study of RTX-321 for the treatment of patients that are HLA-A*02:01 positive with persistent, recurrent, or metastatic, unresectable, HPV 16-positive cancers (including cervical cancer, head and neck cancer – including of the nasal and oral cavities, larynx, hypopharynx, nasopharynx, and oropharynx – and anal cancer)
Status

Recruiting

Key Objectives
  1. Safety Assessment
  2. Pharmacodynamics of RTX-321 will be evaluated through changes in number of CD8+ T-cells in peripheral blood
  3. Anti-tumor activity of RTX-321 measured by Duration of Response (DoR), Progression Free Survival (PFS), Overall Response Rate (ORR) and Overall Survival (OS)

If you are a patient or a loved one interested in learning more about RTX-321 for the treatment of cancer or participating in a clinical trial, please visit:

Patient Access

At Rubius Therapeutics, we are focused on developing an entirely new class of medicine to treat cancer and autoimmune diseases. We are conducting several clinical trials to demonstrate the safety and efficacy of these potential treatments. These investigational treatments have not been approved by regulatory authorities, such as the United States Food and Drug Administration (FDA).

Patient access programs allow patients with immediately life-threatening conditions or serious diseases to gain access to an investigational therapy outside of clinical trials. As we carefully consider the health and well-being of patients and families, our first commitment is to avoid inadvertently doing harm while the safety of our treatments is still being evaluated.

At this time, we are not able to provide access to our investigational therapies outside of a clinical trial setting. We believe the best way to develop safe and effective treatments that have a positive benefit for the largest number of patients is to continue our rigorous clinical development program.

We encourage any person interested in learning more about participating in one of our clinical trials to discuss their eligibility with their physician or to visit www.rubiustrials.com.