Rubius Therapeutics, Inc. (NASDAQ:RUBY), a clinical-stage biopharmaceutical company that is biologically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics™ for the treatment of cancer and autoimmune diseases, today announced significant advances from its RED PLATFORM and across its pipeline of Red Cell Therapeutics (RCTs) at the Company’s first Pipeline and Platform Day.
“Over the course of our presentations, we will highlight the incredible scope and versatility of the programmable RED PLATFORM, enabling targeting of multiple immune pathways via several different modalities, as well as the progress Rubius Therapeutics is making in advancing our clinical-stage cancer therapies, autoimmune programs and manufacturing capabilities,” said Pablo J. Cagnoni, M.D., “Today, for the first time, we will be unveiling preclinical proof of concept data demonstrating tolerance induction with bystander suppression of type 1 diabetes, a T cell-mediated disease. We expect next year to be data rich with several important clinical milestones from our oncology pipeline, including additional clinical results from the single-agent RTX-240 Phase 1 clinical trial in advanced solid tumors and acute myeloid leukemia and initial clinical results from our RTX-321 Phase 1 clinical trial in advanced HPV 16-positive cancers, which we anticipate occurring during the first quarter of 2022.”
Highlights and Progress
RED PLATFORM
- Achieved clinical validation of the RED PLATFORM with initial clinical results from the single-agent RTX-240 Phase 1 clinical trial in advanced solid tumors, reported in March 2021
- RCTs are well tolerated, induce the desired biological effect and generate clinical benefit in certain patients with advanced solid tumors
- Advancing next generation aAPCs with loadable MHC Class I, enabling the presentation of multiple antigens on a single RCT and broadening the potential patient population with a library of HLA types
- Enabling rapid and repeatable parallel generation of therapeutic candidates with the programmable RED PLATFORM
- The platform creates multiple modalities for the treatment of cancer and autoimmune disease and the ability to express hundreds of thousands of copies of therapeutic proteins on or within the cell to access numerous immune pathways
- The platform creates multiple modalities for the treatment of cancer and autoimmune disease and the ability to express hundreds of thousands of copies of therapeutic proteins on or within the cell to access numerous immune pathways
Oncology
Broad Immune Stimulation Approach
RTX-240
- Established clinical proof of concept of RTX-240 in advanced solid tumors, based on initial results reported in March 2021, potentially increasing the likelihood of clinical success across the oncology pipeline
- Escalating the dose of single-agent RTX-240 in the Phase 1 solid tumor clinical trial to three doses of 5e10 followed by one dose 1e10 until disease progression or unacceptable toxicity, based on no dose-limiting toxicities observed to date, a clear dose response in the increase of NK cells and other pharmacodynamic effects
- Additional clinical results are expected from this trial and the Phase 1 arm in relapsed/refractory AML during the first quarter of 2022.
- The Company plans to initiate single-agent RTX-240 Phase 2 expansion cohorts in select solid tumor types during the first quarter of 2022.
- Continuing dose escalation in the RTX-240 Phase 1 combination study with pembrolizumab in patients with advanced solid tumors.
RTX-224
- Planning to initiate the Phase 1 clinical trial of RTX-224 in patients with certain advanced solid tumors during the first quarter of 2022
- Investigational New Drug application cleared
Antigen-Specific Immune Stimulation Approach
RTX-321
- Continuing enrollment in Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers
- Planning to report initial clinical results during the first quarter of 2022
Autoimmune Diseases and Type 1 Diabetes
- Demonstrated tolerance induction and bystander suppression in stringent type 1 diabetes preclinical models
- Established efficacy in the BDC2.5 adoptive transfer model with data supporting that repeated dosing extended duration of disease protection, reverses established inflammation, which is important for the treatment of existing autoimmunity, and induces two types of regulatory T cells, resulting in protection against re-challenge
- Showed efficacy in non-obese diabetes (NOD) preclinical model
- Results at 25 weeks exhibit bystander suppression by delivering only two antigens, indicating the mouse surrogate of RTX-T1D prevented or delayed disease caused by many autoantigens
- These findings are potentially translatable beyond type 1 diabetes to multiple autoimmune diseases, including other Rubius’ high priority target indications, including multiple sclerosis and celiac disease.
Manufacturing
- Increased cells produced per batch by four times in 50L bioreactors from 2020 to 2021, enabling uninterrupted clinical supply for three Phase 1 arms of the RTX-240 clinical trial and Phase 1 RTX-321 trial
- Additional accomplishments include:
- High success rate: greater than 90% lot success rate for RTX-240 and RTX-321 clinical supply in 2021
- Greater than 200 doses administered across three arms of RTX-240 Phase 1 and RTX-321 Phase 1 trials
- High transduction efficiency: greater than 90% of cells are transduced with therapeutic proteins
- Highly consistent protein expression (dual or triple)
- Introduced frozen drug substance for RTX-321 and RTX-224, enabling inventory storage of greater than two years
- Developing frozen drug product to further simplify supply chain with the goal of making our therapies available around the world
- Bringing all product testing in-house to strengthen supply chain and reduce time-to-product release
- Continuing to invest in the platform to improve productivity and efficiency
- Scaling to 200L bioreactors by mid-2022 to support potential pivotal trial and eventual commercialization
