ADVANCING A BROAD AND DIVERSE PIPELINE

Rubius Therapeutics is advancing a broad pipeline of RCTTM product candidates. Our current programs are investigating applications across multiple therapeutic areas—starting with rare enzyme deficiencies, cancer and autoimmune diseases. The U.S. Food and Drug Administration has cleared our Investigational New Drug application (IND) for our first clinical candidate, RTX-134, for the treatment of phenylketonuria.  Additionally, we plan to file an IND for RTX-240 for the treatment of solid tumors by early 2020. In total, we plan to file four to five INDs during 2019 and 2020.

Candidate
Preclinical
IND Enabling
Phase 1
Phase 2
Phase 3

Rare Diseases

Phenylketonuria
IND Cleared
RTX-134

RTX-134 is genetically engineered to express the enzyme phenylalanine ammonia lyase inside the cell to convert phenylalanine into two metabolites, trans-cinnamic acid and ammonia. RTX-134 is designed to treat phenylketonuria (PKU), a rare disease characterized by a buildup of the neurotoxic amino acid, phenylalanine.

Refractory Gout
RTX-Uricase

RTX-Uricase is genetically engineered to express uricase and a uric acid transporter that optimizes uptake of uric acid into the cell. We expect RTX-Uricase to improve a patient’s ability with chronic refractory gout to clear uric acid from the blood.

Homocystinuria
RTX-CBS

RTX-CBS expresses cystathionine beta-synthase (CBS) in the cell in order to replace a patient’s missing or ineffective enzymes for the treatment of homocystinuria. RTX-CBS is expected to rapidly drop total plasma homocysteine (tHcy) to clinically meaningful target levels.

RTX-OxOx
Hyperoxaluria
RTX-OxOx

Candidate
Preclinical
IND Enabling
Phase 1
Phase 2
Phase 3

Cancer

R/R aPD1 Solid Tumors
Estimated IND Filing by Early ‘20
RTX-240

RTX-240, formerly RTX-212, co-expresses 4-1BBL and IL-15TP, a fusion of IL-15 and IL-15 receptor alpha, with the goal of improving anti-tumor activity and overcoming resistance to immunotherapy in patients with solid tumors.

R/R AML Post-HSCT
RTX-240

We plan to conduct a Phase 2 trial of RTX-240, formerly RTX-212, administered to acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT) using the single agent dose determined in our Phase 1 trial of RTX-240 in solid tumors.

R/R aPD1 Solid Tumors
RTX-224

RTX-224 co-expresses 4-1BBL and IL-12 on the cell surface to activate the innate and adaptive immune systems.

HPV+ Solid Tumors
RTX-321 aAPC (HPV+)

RTX-321 is an artificial antigen presenting cell (aAPC) that is designed to induce a tumor-specific immune response by dramatically expanding HPV-positive 16-specific T cells inside a patient’s body. These T cells are then expected to traffic to HPV-positive tumors to deliver a potent anti-tumor effect.

Candidate
Preclinical
IND Enabling
Phase 1
Phase 2
Phase 3

Autoimmune Diseases

RTX-T1D
Type 1 Diabetes
RTX-T1D

RTX-PV
Pemphigus Vulgaris
RTX-PV

THERAPEUTIC AREAS

THE POTENTIAL TO MORE EFFECTIVELY TREAT RARE ENZYME DEFICIENCIES

Many rare diseases are caused by enzyme deficiencies resulting from a genetic defect. Until now, these diseases have been treated with enzyme replacement therapy designed to break down toxic metabolites that accumulate in the body due to the missing or deficient enzyme. The body sometimes recognizes these therapeutics enzymes as foreign and attempts to degrade them before they can do their job. Current therapeutic approaches are often ineffective, poorly tolerated and require frequent infusions.

RCTTM product candidates are engineered to express the necessary enzymes within each cell, shielding them from the immune system. As RCTs circulate, they are expected to break down the toxic metabolites in the blood stream that have accumulated. Compared to current therapeutic approaches, RCTs may have a longer and more sustained treatment effect given the 120-day circulating time of red blood cells and may avoid immune-driven adverse events, including formation of neutralizing antibodies to the therapeutic enzyme, which often result in a reduction in efficacy. We expect RCTs to provide a more efficacious treatment option to patients.

Our lead programs target rare enzyme deficiencies where no available treatment options exist or current treatments may be improved. Initially, we are focusing our efforts on creating RCTs for the potential treatment of phenylketonuria, chronic refractory gout and homocystinuria.

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 co-express combinations of co-stimulatory molecules 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 re-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 pemphigus vulgaris and Type I diabetes, among others.