• Efficacy and safety con­tinue to be a major ad­van­tage, with a very high response rate, no dose limiting toxicities and only a single in­ci­dence of sus­pected cytokine release syn­drome
• P-BCMA-101 clin­i­cal data as well as pre­clin­i­cal data from MUC1C and PSMA solid tumor pro­grams and BCMA allo­geneic pro­gram presented at the CAR-TCR Summit

San Diego, CA (Press Release) – Poseida Therapeutics Inc. (“Poseida”), a clin­i­cal-stage bio­tech­nology com­pany translating best-in-class gene engi­neer­ing tech­nolo­gies into lifesaving cell ther­a­pies, announced data results from the first eleven patients treated in its ongoing Phase 1 study of its P-BCMA-101 stem cell memory chi­meric an­ti­gen re­cep­tor T-cell (CAR-T) prod­uct in re­lapsed / refractory multiple myeloma. All eleven patients remain on study with seven of ten patients evaluable by Inter­na­tional Myeloma Work­ing Group (IMWG) criteria achieving at least a partial response. The remaining patient also dem­onstrated a robust response, but has oligo­secretory disease and was only evaluable by PET. Importantly, unlike pre­vi­ous CAR-T ther­a­pies, P-BCMA-101 is demonstrating exceptional safety, with only one instance of sus­pected cytokine release syn­drome (9%) that was minimal and short-lived. No patients dem­onstrated neurotoxicity and no patients required admission to an intensive care unit or treat­ment with tociluzimab or steroids, interventions typically required during episodes of CRS elicited by other CAR-T ther­a­pies. Enrollment con­tinues in the higher dose cohorts.

“The latest data results show that P-BCMA-101 induces deep responses in a heavily pre­treated pop­u­la­tion with re­lapsed / refractory multiple myeloma, with some patients reaching VGPR and even stringent CR at early efficacy assess­ments,” said Eric Ostertag, M.D., Ph.D., chief exec­u­tive officer of Poseida Therapeutics. “We believe our ad­van­tages of a purified prod­uct, where all cells express the CAR molecule, and a prod­uct with high levels of stem cell memory T cells, producing a more gradual and prolonged immune response against tumor cells, provide a sig­nif­i­cantly better thera­peutic index when com­pared with other CAR-T thera­peutics. We are also en­cour­aged that P-BCMA-101 is demonstrating sig­nif­i­cant efficacy even at doses that have been ineffective for other anti-BCMA CAR-T ther­a­pies and that our response rates con­tinue to im­prove as the dose in­­creases.”

P-BCMA-101 Clinical Data Presented as Late Breaker Today at CAR-TCR Summit

As of August 10th, 2018, eleven patients had been treated across three doses groups with average CAR-T cell doses of 51x10⁶ (n=3), 152x10⁶ (n=7), and 430x10⁶ (n=1). These patients were heavily pre­treated with a median of 6 prior ther­a­pies. The median age was 60, with 73% con­sidered high-risk, in­­clud­ing those with high-risk cytogenetics. Peak T-cell expansion was observed be­tween days 14 and 21, which is more gradual than the 5-14 day peak expansion seen with other CAR-T ther­a­pies and was asso­ci­ated with less acute cytokine release and other adverse effects.

A favorable safety profile con­tinues to be observed. The single instance of sus­pected cytokine release syn­drome occurred in a patient in the second cohort and rapidly re­solved without treat­ment with tociluzimab or steroids. Consistent with the minimal evi­dence of CRS symp­toms, patients’ bio­­markers of CRS, in­­clud­ing IL-6 levels, are demonstrating peak levels lower than those seen in patients from other anti-BCMA CAR-T trials. Common adverse events were neu­tro­penia and thrombo­cytopenia, which are typical for CAR-T and myeloma studies con­sidering the disease, preconditioning chemo­therapy and prior chemo­therapy regi­mens. No dose limiting toxicities were observed at any dose. Enrollment require­ments have been achieved in the third dose cohort and enrollment is ex­pec­ted to con­tinue into the fourth and fifth dose cohorts per protocol.

This open-label, multi­center, single-ascending dose, Phase 1 study is designed to assess the safety of P-BCMA-101 in up to 40 subjects with re­lapsed and/or refractory multiple myeloma. The pri­mary objective of this study is to de­ter­mine the safety and maximum-tolerated dose of P-BCMA-101. Secondary objectives in­clude anti-myeloma effect of P-BCMA-101. This study is funded in part by the California Institute for Regenerative Medicine. Additional in­­for­ma­tion about the Phase 1 clin­i­cal study of P-BCMA-101 is avail­able at www.clinicaltrials.gov using identifier: NCT03288493

Preclinical Presentations at CAR-TCR Summit

A Stem Cell Memory CAR-T Therapy for Epithelial-Derived (MUC1-C) Solid Tumors

• Poseida is devel­op­ing an au­tol­o­gous stem cell memory CAR-T ther­apy targeting the C terminal region of Mucin-1 (MUC1-C), which is highly ex­pressed on most epithelial-derived cancers, in­­clud­ing breast, lung, renal cell, colorectal, ovarian and pancreatic cancers, among others.
• P-MUC1C-101 in­cludes the same features of Poseida’s au­tol­o­gous P-BCMA-101 CAR-T ther­apy, in­­clud­ing a selection gene to create a pure CAR-positive prod­uct, a high level of stem cell memory T-cells, and a safety switch.
• P-MUC1C-101 elicited tumor elimination across multiple tumor types, in­­clud­ing rapid and com­plete elimination of estab­lish­ed tumors in a mouse xenograft model of breast cancer.
• Oral presentation by Dr. Devon J. Shedlock, vice pres­i­dent of pre­clin­i­cal devel­op­ment at Poseida
• CAR-TCR Discovery Track; September 6^th, 2:35 p.m. ET

Manufacture of Allogeneic “Universal Donor” CAR-T Therapies using piggyBac™ and Cas-CLOVER™ Gene Editing Technologies

• Poseida is devel­op­ing an allo­geneic, or universal donor, CAR-T Therapy called P-BCMA-ALLO1 targeting BCMA. It in­cludes the same features of Poseida’s au­tol­o­gous P-BCMA-101 CAR-T ther­apy, in­­clud­ing a selection gene for prod­uct purity, a high level of stem cell memory T-cells, and a safety switch.
• TCR and MHC1 are knocked out using Poseida’s Cas-CLOVER™ high-fidelity gene editing sys­tem, eliminating alloreactivity (both graft-versus-host and host-versus-graft) to below the limit of detection.
• Integration of Poseida’s “booster molecules” dem­onstrated ability to mitigate poten­tial deficiencies of TCR knock out in CAR-T cells and suc­cess­fully im­proves T-cell expansion.
• P-BCMA-ALLO1 cells exhibit com­parable levels of BCMA-specific CAR ex­pres­sion and com­parable an­ti­gen-specific functionality to the au­tol­o­gous P-BCMA-101 prod­uct cur­rently under clin­i­cal in­ves­ti­ga­tion.
• Oral presentation by Dr. Burton E. Barnett, research scientist at Poseida
• CAR-TCR Manufacturing Track; September 6^th, 4:10 p.m. ET

How Can We Create An Allogeneic, Virus Free Manufacturing Process?

• Panel discussion by Dr. Burton E. Barnett, research scientist at Poseida
• CAR-TCR Manufacturing Track; September 6th, 2:35pm ET

PSMA-specific CAR-T Memory Stem Cell Therapy Eliminates Solid Tumors in Multiple Prostate Cancer Models

• Poseida is devel­op­ing an au­tol­o­gous stem cell memory CAR-T ther­apy targeting PSMA, which is overexpressed in most metastatic prostate cancers.
• P-PSMA-101 in­cludes the same features of Poseida’s au­tol­o­gous P-BCMA-101 CAR-T ther­apy, in­­clud­ing a selection gene for prod­uct purity, a high level of stem cell memory T-cells, and a safety switch.
• The Centyrin binder used to con­struct the P-PSMA-101 CAR exhibited exquisite specificity for PSMA fol­low­ing a study interrogating an extensive library of over 5,400 proteins ex­pressed on the surface of human cells.
• P-PSMA-101 elicited tumor elimination in two dif­fer­en­t mouse xenograft solid tumor models in­­clud­ing one implanted with human LNCaP, a human cell line derived from castrate-resistant metastatic prostate cancer that endogenously expresses PSMA and another modeling bone metastasis using a second cell line derived from castrate-resistant metastatic prostate cancer, called PC-3, which was engi­neered to express PSMA.
• Poster presentation by Dr. Jenessa B. Smith, research scientist at Poseida
• Scientific Poster Session; September 6^th, 8:00 a.m. ET

About P-BCMA-101

P-BCMA-101 is a CAR-T immuno­therapy designed to supercharge a patient’s own T cells to safely and effectively elim­i­nate tumor cells carrying B cell maturation an­ti­gen (BCMA), which is ex­pressed on essentially all multiple myeloma tumor cells. P-BCMA-101 modifies a patient’s T cells using piggyBac™, which enables several desirable features, in­­clud­ing:

• T stem cell memory: P-BCMA-101 is com­prised of a high level of stem cell memory T-cells (Tscm), resulting in unprecedented durability of response without re-administration of prod­uct in multiple pre­clin­i­cal studies.
• Pure prod­uct: The addi­tion of a human-derived pos­i­tive selection gene results in a prod­uct that is composed almost entirely of modified CAR-T cells in contrast with lentivirus-based prod­ucts, which are generally 5-30% pure. The higher purity of the prod­uct may also result in less toxicity.
• Safety: piggyBac™ is non-oncogenic and has a safer integration profile than lentivirus. In addi­tion, a human-derived safety switch is added such that P-BCMA-101 can be rapidly attenuated or elim­i­nated if sig­nif­i­cant side effects occur.

About Poseida Therapeutics, Inc. 

Poseida Therapeutics is a clin­i­cal-stage bio­technology com­pany translating best-in-class gene engi­neer­ing tech­nolo­gies into lifesaving cell ther­a­pies. The com­pany is devel­op­ing CAR T-cell immuno­therapies for multiple myeloma, prostate and other cancer types, as well as gene ther­a­pies for orphan diseases. P-BCMA-101 is Poseida’s lead CAR-T ther­apy cur­rently in Phase 1 clin­i­cal devel­op­ment for the treat­ment of multiple myeloma. Poseida has assembled a suite of industry-leading gene engi­neer­ing tech­nolo­gies, in­­clud­ing the piggyBac™ DNA Modification System, TAL-CLOVER™ and Cas-CLOVER™ site-specific nucleases, and Footprint-Free™ Gene Editing (FFGE). For more in­­for­ma­tion, visit www.poseida.com.

Source: Poseida.