On January 10, 2022 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, reported that provided an overview of the Company’s achievements in 2021 and outlined its objectives for 2022 (Press release, Rubius Therapeutics, JAN 10, 2022, View Source [SID1234598466]). Pablo J. Cagnoni, M.D., president and chief executive officer, will present these updates on Wednesday, January 12, 2022, at 8:15 a.m. EST at the virtual 40th Annual J.P. Morgan Healthcare Conference.

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"In 2021, Rubius Therapeutics demonstrated strong execution in advancing our clinical oncology pipeline and showing preclinical proof of concept of our tolerance induction approach in autoimmunity that could extend well beyond type 1 diabetes to other T cell-mediated diseases," said Pablo J. Cagnoni, M.D., president and chief executive officer, of Rubius Therapeutics. "With the initial clinical results from the Phase 1 clinical trial of RTX-240 in patients with advanced solid tumors reported in March 2021, we provided clinical validation of the RED PLATFORM and increased our likelihood of success across our entire oncology pipeline of Red Cell Therapeutics. With multiple data milestones on the horizon in 2022, we are on the cusp of potentially further validating the RED PLATFORM and benefiting an even greater number of patients."

Anticipated 2022 Catalysts and Operational Objectives

Present additional clinical results from the Phase 1 arm of the RTX-240 Phase 1/2 clinical trial in advanced solid tumors and the Phase 1 arm in relapsed/refractory acute myeloid leukemia (AML) during the first quarter of 2022
Initiate RTX-240 Phase 2 expansion cohorts in select solid tumor types during the first quarter of 2022
Report initial clinical results from the Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers during the second half of 2022
Present initial clinical data from the Phase 1 arm of the RTX-240 clinical trial in combination with pembrolizumab in patients with advanced solid tumors during the second half of 2022
Scale to 200L bioreactors by mid-2022 to support potential pivotal trial and eventual commercialization
2021 Achievements and Operational Updates

RED PLATFORM

Enabling rapid and repeatable parallel generation of therapeutic candidates with the programmable RED PLATFORM
1,000 different therapeutic proteins biologically engineered since platform inception, underscoring the highly versatile and programmable nature of the 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
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 artificial antigen-presenting cells (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
Oncology

Broad Immune Stimulation

RTX-240

RTX-240 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 NK and CD8+ memory T cells to generate a potent anti-tumor response.

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
Escalated the dose of single-agent RTX-240 in the Phase 1 solid tumor clinical trial to three doses of 5e10 cells followed by 1e10 cells 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 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 with initial clinical data expected during the second half of 2022
RTX-224

RTX-224 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to express hundreds of thousands of copies of 4-1BBL and interleukin-12 (IL-12) on the cell surface. While the lead oncology product candidate, RTX-240, is designed to broadly stimulate the immune system by activating and expanding NK and CD8+ memory T cells, RTX-224 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 known responsiveness to checkpoint inhibitors.

Expect to begin dosing patients in the Phase 1/2 clinical trial of RTX-224 in selected relapsed/refractory or locally advanced solid tumors during the first quarter of 2022
Select cancers include non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, urothelial (bladder) carcinoma and triple-negative breast cancer
Presented preclinical data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting in November 2021, demonstrating that the mouse surrogate of RTX-224, mRBC-224, generated potent anti-tumor activity in B16F10 melanoma models, intravenously and subcutaneously, that was associated with pharmacodynamic changes in the tumors, including activated CD8 + T cells, NK cells and macrophages
Antigen-Specific Immune Stimulation

RTX-321 Artificial Antigen-Presenting Cell (aAPC) Development Program for Human Papillomavirus (HPV) 16-Positive Cancers

RTX-321 is an allogeneic, off-the-shelf artificial 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 class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.

Continuing enrollment in the Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers
Based on no dose limiting toxicities to date, the Company plans to dose escalate beyond the current cohort of 1e10 cells
Plan to report initial clinical results during the second half of 2022
Autoimmune Diseases and Type 1 Diabetes

Red Cell Therapeutics for the treatment of autoimmune disease are biologically engineered to express proteins and peptides inside the cell and are designed to be phagocytized, or ingested, by dendritic cells or macrophages to induce tolerance, retraining the immune system to no longer recognize these self-antigens as foreign.

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, reversed established inflammation, which is important for the treatment of existing autoimmunity, and induced 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.
Fully Owned 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
Hundreds of 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
Listen to the Webcast

A live audio webcast of Dr. Cagnoni’s presentation will be available on January 12, 2022, at 8:15 a.m. EST within the Investors & Media section of the Rubius Therapeutics website. An archived replay will be accessible for 30 days following the event.