|Candidate||Preclinical||IND-Enabling||Phase 1||Phase 2||Phase 3|
|CAR-T for Oncology|
|Dual Car (BCMA/CD19)|
|Dual CAR (Undisclosed)|
|B - Cell||Dual CAR (CD19/CD20)|
|Liver Directed Gene Therapies|
|Ornithine Transcarbamylase (OTC) Deficiency||P-OTC-101|
|Methylmalonic Acidemia (MMA)||P-MMUT-101|
|CAR-T for Oncology|
|P-BCMA-101 - Auto||Phase 2|
|P-BCMA-ALL01 - Allo||IND-Enabling|
|Dual Car (BCMA/CD19) - Allo||Preclinical|
|P-PSMA-101 - Auto||Phase 1|
|P-PSMA-ALL01 - Allo||Preclinical|
|P-MUC1C-ALLO1 - Allo||IND-Enabling|
|Dual CAR (Undisclosed) - Allo||Preclinical|
|B - Cell|
|Dual CAR (CD19/CD20) - Allo||Preclinical|
|Liver Directed Gene Therapies|
|Ornithine Transcarbamylase (OTC) Deficiency|
|P-OTC-101 - GT||Preclinical|
|Methylmalonic Acidemia (MMA)|
|P-MMUT-101 - GT||Preclinical|
|P-FVIII-101 - GT||Preclinical|
We are developing autologous product candidates in multiple myeloma and prostate cancer. Our autologous CAR-T product candidates are developed using our piggyBac DNA Modification System to modify a patient’s own cells to treat their disease. We intend to leverage what we learn from our autologous programs to inform and improve our allogeneic programs.
Our most advanced product candidate, P-BCMA-101, is an autologous CAR-T targeting B cell maturation antigen, or BCMA. We are currently evaluating P-BCMA-101 in a potentially registrational Phase 2 clinical trial and expanded Phase 1 clinical trial for the treatment of patients with relapsed/refractory multiple myeloma in the outpatient setting. Interim results are encouraging, with strong response rates and duration of responses. We have also observed a highly differentiated tolerability profile compared to other CAR-T approaches, with very low levels of CRS and almost no neurotoxicity. As a result of this tolerability profile, we initiated our Phase 2 clinical trial and Phase 1 expansion trial on a fully outpatient basis.
This is our solid tumor autologous CAR-T product candidate targeting prostate-specific membrane antigen, or PSMA, being developed to treat patients with metastatic castrate resistant prostate cancer, or mCRPC. In preclinical studies, P-PSMA-101 has demonstrated elimination of tumor cells to undetectable levels in 100% of animals, with only one incidence of relapse in the lower dose. To our knowledge based on published literature, no other product candidate has shown complete solid tumor elimination in this preclinical model. A Phase 1 dose escalation trial of P-PSMA-101 is ongoing.
Our robust allogeneic CAR-T product candidates will 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 our first allogeneic CAR-T product candidate targeting BCMA, being developed 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.
This is an allogeneic CAR-T product candidate in preclinical 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 MUC1C. 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.
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.
We have a number of gene therapies in development addressing rare and life-threatening diseases including Ornithine Transcarbamylase (OTC) deficiency and Methylmalonic Acidemia (MMA), two genetic liver diseases which are usually diagnosed in the early neonatal period. Our initial focus also includes utilizing piggyBac in combination with nanoparticle technology in development of potential treatments in the future.
P-OTC-101 – Liver Directed Gene Therapy
P-OTC-101 is a liver-directed gene therapy combining piggyBac technology with AAV for the in vivo treatment of OTC deficiency. OTC deficiency 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 increase of approximately 100 X in OTC levels with a single injection of a piggyBac in combination with AAV to deliver an OTC therapeutic transgene compared to AAV-transgene alone, significantly beyond what would be expected to correct the deficiency in humans. We anticipate an IND filing and initiation of a Phase 1 clinical trial for P-OTC-101 in 2022.
P-MMUT-101 – Liver Directed Gene Therapy
P-MMUT-101 combines piggyBac technology with AAV for the treatment of Methylmalonic Acidemia (MMA). People with this rare, genetic disorder are unable to produce an enzyme needed to break down and use certain proteins and fats found in food. This causes a buildup of acids and other harmful substances in the blood, urine, and other cells, including brain cells. MMA is an inborn error of metabolism caused by mutations in genes affecting amino acid metabolism pathways, which can lead to irreparable and life-threatening kidney, liver, and brain damage.
P-FVIII-101 – PiggyBac Factor VIII Nanoparticle
PiggyBac Factor VIII 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 demonstrates an ability to correct this deficiency to near normal levels in a juvenile mouse model using nanoparticle delivery of our piggyBac Factor VIII product candidate. Preclinical studies are ongoing that will inform the development plan and timeline to IND.