|Indication||Candidate||Discovery||Preclinical||IND-Enabling||Phase 1||Phase 2||Programs|
|CAR-T for Oncology|
|B - Cell||P-CD19CD20-ALLO1|
|CAR-T for Oncology|
|P-MUC1C-ALLO1 - Allo||Phase 1|
|P-PSMA-ALLO1 - Allo||Preclinical|
|Dual Undisclosed - Allo||Preclinical|
|P-BCMA-ALLO1 - Allo||Phase 1|
|P-BCMACD19-ALLO1 - Allo||Preclinical|
|B - Cell|
|P-CD19CD20-ALLO1 - Allo||IND-Enabling|
|P-CD70-ALLO1 - Allo||Preclinical|
|Ornithine Transcarbamylase Deficiency||P-OTC-101|
|Rare Liver Disease||TBD|
|Liver Directed||2 Undisclosed programs|
|HSC-DIRECTED||2 Undisclosed programs|
|Ornithine Transcarbamylase Deficiency|
|P-OTC-101 - GT||Preclinical|
|Rare Liver Disease|
|TBD - GT||Discovery|
|P-FVIII-101 - GT||Preclinical|
|2 Undisclosed programs - GT||Discovery|
|2 Undisclosed programs - GT||Discovery|
Our robust allogeneic CAR-T product candidates are designed to provide a safe and efficacious off-the-shelf treatment for patients with multiple myeloma, B cell malignancies, and multiple solid tumors. The large cargo capacity of our piggyBac DNA Modification System also allows us the capability to develop Dual CARs to address multiple targets simultaneously for greater targeting capacity to further drive efficacy and durability, particularly in solid tumor indications.
Our allogeneic products leverage:
- A high percentage of TSCM cells
- Efficient editing of resting T cells – resulting in single, multiplexed gene editing and purification
- Reduced or fully eliminated alloreactivity
- Booster molecules to drive scale, giving us the potential to treat hundreds of patients from a single manufacturing run
This is an allogeneic CAR-T product candidate in development for multiple solid tumor indications. We believe P-MUC1C-ALLO1 has the potential to treat a wide range of solid tumors derived from epithelial cells, such as breast, colorectal, lung, ovarian, pancreatic, and renal cancers, as well as other cancers expressing a cancer-specific form of the Mucin 1 protein, or MUC1-C. We have designed P-MUC1C-ALLO1 to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity. We have demonstrated the elimination of tumor cells to undetectable levels in two preclinical models of breast cancer and a preclinical model of ovarian cancer.
This allogeneic CAR-T product candidate targets PSMA to treat patients with mCRPC. We have designed P-PSMA-ALLO1 to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity. We plan to incorporate our learnings from our P-PSMA-101 autologous program into the P-PSMA-ALLO1 allogeneic program including an improved VH binding technology targeting PSMA.
Dual CAR Allogeneic Programs
We have a portfolio of allogeneic Dual CAR product candidates, which contain two fully functional CAR molecules to target cells that express at least one of the two intended targets, that are in preclinical studies. We believe that our ability to include two or more fully functional CAR molecules into a T cell could be a significant competitive advantage.
This allogeneic CAR-T product candidate targeting BCMA is being developed in partnership with Roche to treat relapsed/refractory multiple myeloma patients. We have designed P-BCMA-ALLO1 to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity. We have incorporated all of our learnings from our P-BCMA-101 autologous program into the P-BCMA-ALLO1 allogeneic program including an improved VH binding technology targeting BCMA.
We have a number of gene therapies in development addressing rare and life-threatening diseases including Ornithine Transcarbamylase Deficiency (OTCD), Hemophilia A and Phenylketonuria (PKU),three genetic liver diseases that are usually diagnosed in the early neonatal period. Our initial focus also includes utilizing Super piggyBac in combination with AAV or nanoparticle technology to develop future potential treatments for patients in need.
P-OTC-101 – Hybrid (AAV+LNP) Gene Therapy
P-OTC-101 is a liver-directed gene therapy combining piggyBac technology with AAV for the in vivo treatment of OTC Deficiency (OTCD). OTCD is an often fatal or morbid urea cycle disease caused by congenital mutations in the OTC gene with a high unmet medical need. In a neonatal mouse model of severe OTC deficiency, we observed an approximate 100-fold increase in OTC levels with a single injection of super piggyBac in combination with adeno-associated virus (AAV) to deliver an OTC therapeutic transgene compared to AAV-transgene alone, significantly beyond what would be expected to correct the deficiency in humans.
P-FVIII-101 – Non-viral Factor VIII Gene Therapy
P-FVIII-101, our first fully non-viral gene therapy program, is a liver-directed gene therapy combining piggyBac technology with our nanoparticle delivery technology for the in vivo treatment of Hemophilia A. Hemophilia A is a bleeding disorder caused by a deficiency in Factor VIII production with a high unmet need. Our preclinical data has demonstrated the potential ability to correct this deficiency to near normal levels in a juvenile mouse model using nanoparticle delivery of our Super piggyBac Factor VIII product candidate. This product is potentially re-dosable, with proof-of-concept pre-clinical models showing that the product candidate can be administered repeatedly to titrate to therapeutic threshold. Preclinical development is currently ongoing in partnership with Takeda.
P-PAH-101 – Hybrid (AAV+LNP) Gene Therapy
P-PAH-101 is a liver-directed gene therapy to treat Phenylketonuria (PKU). PKU is an inherited genetic disorder caused by mutations in the PAH (phenylalanine hydroxylase) gene resulting in buildup of phenylalanine in the body. If left untreated, PKU can affect a person’s cognitive development. P-PAH-101 utilizes Super piggyBac technology combined with a hybrid adeno-associated virus (AAV) and nanoparticle delivery system. Our preclinical data has demonstrated the potential to resolve phenylalanine to normal levels following a single treatment in juvenile and adult mice. Preclinical development is currently ongoing in partnership with Takeda.