UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification No.) |
| |
||||
| (Address of principal executive offices) |
(Zip Code) | |||
Registrant’s telephone number, including area code:
N/A
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading |
Name of each exchange on which registered | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
| Item 7.01 | Regulation FD Disclosure. |
On December 6, 2022, Poseida Therapeutics, Inc. (the “Company”) issued a press release announcing the publication of two posters, which present early data from the Company’s Phase 1 clinical trials of P-MUC1C-ALLO1 and P-BCMA-ALLO1. The posters will be presented at the European Society for Medical Oncology Immuno-Oncology Annual Congress taking place in Geneva, Switzerland and online from December 7-9, 2022. A copy of the press release and the posters to be presented are attached as Exhibits 99.1, 99.2 and 99.3, respectively, to this report.
The information in this Item 7.01 of this report (including Exhibit 99.1, Exhibit 99.2 and Exhibit 99.3) is furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information shall not be deemed incorporated by reference into any other filing with the Securities and Exchange Commission made by the Company, whether made before or after today’s date, regardless of any general incorporation language in such filing, except as shall be expressly set forth by specific references in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Poseida Therapeutics, Inc. | ||||||
| Date: December 6, 2022 | By: | /s/ Harry J. Leonhardt, Esq. | ||||
| Name: | Harry J. Leonhardt, Esq. | |||||
| Title: | General Counsel, Chief Compliance Officer & Corporate Secretary | |||||
Exhibit 99.1
|
Poseida Therapeutics to Present Early Data from Phase 1 Trials of P-MUC1C-ALLO1 and P-BCMA-ALLO1 at ESMO Immuno-Oncology 2022 Annual Congress
P-MUC1C-ALLO1 and P-BCMA-ALLO1 were well tolerated, with no dose-limiting toxicities (DLTs), cytokine release syndrome (CRS), graft vs host disease (GVHD) or immune effector cell-associated neurotoxicity syndrome (ICANS)
P-MUC1C-ALLO1 demonstrated encouraging clinical activity including an objective partial response in a breast cancer patient at the lowest dose
P-BCMA-ALLO1 demonstrated responses in heavily pre-treated patients with relapsed/refractory multiple myeloma at the lowest CAR-T dose tested including in patients who had failed prior BCMA-targeted therapy and patients with high-risk disease
SAN DIEGO, December 6, 2022 — Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, today announced it will present early clinical results from its Phase 1 clinical trials of P-MUC1C-ALLO1 and P-BCMA-ALLO1 at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) 2022 Annual Congress, taking place in Geneva, Switzerland and online from December 7-9, 2022.
“These early data being presented at ESMO I-O for our first two fully allogeneic programs reinforce our belief that our technology and approach have the potential to deliver differentiated off-the-shelf CAR-T cell therapies to patients fighting cancer,” said Mark Gergen, Chief Executive Officer of Poseida Therapeutics. “While it is still quite early in both trials, we have seen encouraging responses in both P-MUC1C-ALLO1 and P-BCMA-ALLO1 at the lowest doses as well as favorable tolerability. As we look ahead, we are excited to continue enrolling patients at higher dose levels and explore additional strategies to optimize the therapeutic index, including redosing, cyclic dosing, novel preconditioning regimens and combination therapies. We look forward to providing updates at a medical meeting in 2023.”
Both posters will be presented at ESMO I-O on Thursday, December 8, 2022 at 12:30-1:15 PM CET in Foyer ABC at the Palexpo Exhibition Centre in Geneva and are now available on the Poseida website at www.poseida.com.
In the poster titled “Development of an allogeneic CAR-T targeting MUC1-C (MUC1, cell surface associated, C-terminal) for epithelial derived tumors” (abstract #407, presentation 46P), David Oh, M.D., Ph.D., Assistant Professor, University of California, San Francisco, will highlight:
| • | As of the cutoff date of November 14, 2022, the study had dosed seven patients with epithelial-derived cancers, including esophageal, colorectal, breast, pancreatic and prostate carcinomas, of which four were evaluable for response. |
|
|
| • | Only one patient with breast cancer has been dosed to date; this patient with HR+, HER2- breast cancer, with four prior lines of treatment, achieved a partial response at a dose of 0.75x106 cells/kg. |
| • | Two other patients with heavily pretreated gastrointestinal tumors (colorectal and pancreatic cancer) achieved stable disease at a dose of 0.75x106 cells/kg and 2x106 cells/kg each. |
| • | P-MUC1C-ALLO1 was safe and well tolerated, with no DLTs, CRS, GVHD or ICANS. |
“We are very encouraged by these early data highlighting initial safety and tolerability as well as signs of clinical activity of P-MUC1C-ALLO1 even at very low doses,” said Dr. Oh, an investigator on the trial. “Importantly, for a novel target such as MUC1-C it has been a key focus to monitor for any evidence of on-target off-tumor toxicity, and we are pleased that we have not observed any such significant toxicity to date. Overall, we believe that these data support MUC1-C as a target with the potential to address the significant unmet need in patients with advanced carcinomas. We look forward to continuing to evaluate the safety, efficacy and durability of responses as we continue to enroll additional patients into the study.”
In the poster titled “Phase 1 Study to Assess the Safety and Efficacy of P-BCMA-ALLO1, a Fully Allogeneic CAR-T Therapy, In Patients with Relapsed/Refractory Multiple Myeloma (RRMM)” (abstract #705, presentation 47P), Mehmet Hakan Kocoglu, M.D., Assistant Professor, University of Maryland Medical Center, will highlight:
| • | As of the cutoff date of November 11, 2022, the study had dosed 10 patients with relapsed/refractory (R/R) multiple myeloma, Of these ten patients, six are evaluable for response (all at the lowest dose level of 0.75 X 106 cells/kg). |
| • | The response evaluable patients were heavily pre-treated, having received an average of 6.5 prior lines of therapy with a median time since diagnosis of 5 years. Three patients had previously received BCMA-targeted therapy and four patients had high-risk cytogenetics, of which two had p53 deletions. |
| • | As of the cutoff date, P-BCMA-ALLO1 achieved a 50% (3/6) overall response rate, with a 66% (2/3) ORR in patients who had previously received BCMA-targeted therapy and a 50% (2/4) ORR in patients with high-risk cytogenetics. |
| • | Of the three responders in the first cohort (0.75x106 cells/kg), two patients were partial responses and one patient achieved a very good partial response. |
| • | P-BCMA-ALLO1 was extremely well tolerated. There were no cases of CRS, GVHD or ICANS. No DLTs were observed. There was one case of febrile neutropenia. |
“To date, P-BCMA-ALLO1 has demonstrated a favorable safety and tolerability profile in patients with R/R multiple myeloma. We have also observed encouraging efficacy signals even at the lowest doses highlighting the potential of Poseida’s proprietary genetic editing platforms in allogeneic cell therapies,” said Dr. Kocoglu, an investigator on the trial. “In particular, we have seen responses in patients with p53 mutations, a known marker for aggressive multiple myeloma as well as in patients who had received prior BCMA-targeted therapy. These early results support the potential of P-BCMA-ALLO1 to treat a broad patient population with an off-the-shelf CAR-T therapy and we look forward to continuing enrollment in the study.”
|
|
About P-MUC1C-ALLO1
P-MUC1C-ALLO1 is an allogeneic CAR-T product candidate in Phase 1 development for multiple solid tumor indications. Poseida believes P-MUC1C-ALLO1 has the potential to treat a wide range of solid tumors derived from epithelial cells, such as breast, ovarian, colorectal, lung, pancreatic and renal carcinomas, as well as other cancers expressing a cancer-specific form of the Mucin 1 protein, or MUC1-C. P-MUC1C-ALLO1 is designed to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity. Poseida has demonstrated the elimination of tumor cells to undetectable levels in preclinical models of both breast and ovarian cancer. Additional information about the Phase 1 study is available at www.clinicaltrials.gov using identifier: NCT05239143.
About P-BCMA-ALLO1
P-BCMA-ALLO1 is an allogeneic CAR-T product candidate, partnered with Roche, targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma in Phase 1 development. In vitro and in vivo P-BCMA-ALLO1 preclinical studies showed effective, targeted cancer cell killing and cytokine secretion, with similar or superior anti-tumor efficacy compared to an autologous CAR-T therapy. Additional information about the Phase 1 study is available at www.clinicaltrials.gov using identifier: NCT04960579.
About Poseida Therapeutics, Inc.
Poseida Therapeutics is a clinical-stage biopharmaceutical company advancing differentiated cell and gene therapies with the capacity to cure certain cancers and rare diseases. The Company’s pipeline includes allogeneic CAR-T cell therapy product candidates for both solid and liquid tumors as well as in vivo gene therapy product candidates that address patient populations with high unmet medical need. Poseida’s approach to cell and gene therapies is based on its proprietary genetic editing platforms, including its non-viral Super piggyBac® DNA Delivery System, Cas-CLOVER™ Site-Specific Gene Editing System and nanoparticle and hybrid gene delivery technologies. The Company has formed global strategic collaborations with Roche and Takeda to unlock the promise of cell and gene therapies for patients. Learn more at www.poseida.com and connect with Poseida on Twitter and LinkedIn.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, expected plans with respect to clinical trials, including timing of clinical data updates; the potential benefits of Poseida’s technology platforms and product candidates; and Poseida’s plans and strategy with respect to developing its technologies and product candidates. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon Poseida’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, Poseida’s reliance on third parties for various aspects of its business; risks and uncertainties associated with development and regulatory approval of novel product candidates in the biopharmaceutical industry; Poseida’s ability to retain key scientific or management personnel; and the other risks described in Poseida’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Poseida undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.
|
|
| Investor Contact: | Media Contact: | |
| Alex Lobo | Sarah Thailing | |
| Stern Investor Relations | Senior Director, Corporate Communications and IR | |
| IR@poseida.com | Poseida Therapeutics, Inc. | |
| PR@poseida.com |
Exhibit 99.2
46P—Development of an allogeneic CAR-T targeting MUC1-C (MUC1, cell surface associated, C-terminal) for epithelial derived tumors David Y. Oh,1 Jason T. Henry,2 Joaquina Baranda,3 Ecaterina E. Dumbrava,4 Ezra Cohen,5 Rajesh Belani,6 Jeff D. Eskew,6 Joanne McCaigue,6 Hamid Namini,6 Christopher E. Martin,6 Ann Murphy,6 Eric Ostertag,6 Julia Coronella,6 Devon J. Shedlock,6 Ildefonso Rodriguez-Rivera,7 1University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; 2Sarah Cannon Research Institute at HealthOne, Denver, CO; 3University of Kansas Cancer Center, Kansas City, KS; 4MD Anderson Cancer Center, Houston, TX; 5University of California San Diego, San Diego, CA; 6Poseida Therapeutics, Inc., San Diego, CA; 7NEXT Oncology, San Antonio, TX BACKGROUND PRECLINICAL RATIONALE CLINICAL STUDY METHODS AND DESIGN PHASE 1 DOSE-ESCALATION CLINICAL RESULTS Topic Detail * • Most solid tumors are of epithelial origin and express mucin 1 (MUC1) and its C-terminal domain MUC1-C (MUC1, Patient demographics and characteristics Can P-MUC1C-ALLO1 Infiltrate into Solid Tumor? Study information Phase 1, dose escalation, and expanded cohort study of P-MUC1C-ALLO1 in adults with advanced or cell surface associated, C-terminal), such as breast, ovarian, prostate, colorectal, pancreatic, gastric, esophageal, metastatic solid tumors (NCT05239143). The study will include 15 years of follow-up and evaluate the nasopharyngeal, as well as non-small cell lung cancer, renal cell carcinoma, head-and-neck squamous cell safety, MTD, and antitumor effect of P-MUC1C-ALLO1 6 CAR-T cells administered, cells/kg Mean (min, max) x 10 Patients, n carcinoma, and others Study design Part 1: Standard 3+3 design of dose-escalating cohorts 6 Cohort 1: 0.75 x 10 single infusion 74.15 (47.93, 96.98) 3 • There have been multiple clinical-stage therapeutics targeting MUC1, including chimeric antigen receptor (CAR)-T Arm A (SA): single dose after cy/flu lymphodepletion Arm B (CYC): multiple doses in cycles q2W after cy/flu lymphodepletion with 2 additional Cohort 2: 2.0 x 106 single infusion 164.15 (103.88 / 203.56) 3 therapies, antibody-drug conjugates, and bispecific T-cell engagers which have thus far demonstrated little lymphodepletion in cycles 6-week intervals evidence for “on-target, off-tumor” toxicity1-3 Parameter (n=6) Arm C (SA-RIT): singe dose after cy/flu plus rituximab lymphodepletion • MUC1-C is expressed broadly and accessibly throughout tumor tissue due to the loss of cell polarity, one of the Arm D (CYC-RIT): multiple doses in cycles q2W after cy/flu/rit lymphodepletion with 2 additional Age, median (min, max), years 61 (59, 68) lymphodepletion in cycles 6-week intervals hallmarks of tumorigenesis Part 2: Time since diagnosis, median (min, max), years 4.1 (1.08, 10.13) • We have developed a fully allogeneic CAR-T cell therapy, called P-MUC1C-ALLO1, that targets a MUC1-C epitope. P- RP2D at MTD in groups of up to 15 patients with defined characteristics Baseline ECOG performance status, 0/1, n (%) 3 (50%) / 3 (50%) MUC1C-ALLO1 is manufactured using non-viral transposon-based integration (piggyBac® DNA Delivery System), Study patient Adults with confirmed unresectable, locally advanced or metastatic epithelial-derived solid tumors population refractory to standard of care therapy or ineligible or refused another existing treatment option Prior therapy resulting in a highly enriched T stem cell memory (TSCM) product, and is gene edited with Cas-CLOVER to knock out B2M and TRBC. P-MUC1C-ALLO1 administration resulted in complete elimination of solid tumors in murine models Proposed sample size Up to 100 patients (including up to 40 in the expansion) No. of prior regimens, all patients (n=6): median (min, max) 4 (2, 6) Evaluation criteria: Safety/feasibility: AEs, labs, CRS, neurotoxicity, and MAS/HLH4 • This first-in-human Phase 1 clinical trial is evaluating a CAR-T in epithelial-based solid tumors Cohort Patient Tumor Lines of prior Last efficacy, safety, and Efficacy: RECIST v1.1 and secondarily iRECIST; ORR, TTR, DOR, PFS, OS, CTCs, P-MUC1C-ALLO1 cells Sex other variables (vectors/clonality) # type therapy, n therapy P-MUC1C-ALLO1 is highly enriched for T stem cell memory CAR-Ts * Exploratory MUC1-C expression in tumor biopsies and by related markers CA15-3 and CA27-29. P-MUC1C-ALLO1 cell 1 1 M Esophageal adenocarcinoma 3 Ramucirumab/Taxol kinetics and phenotype including b2M expression; immunogenicity in context of patient-donor match 1 2 M Colorectal 6 Investigational STING agonist metrics. Cytokine correlates of lymphodepletion, safety, and efficacy Massive P-MUC1C-ALLO1 Tumor Infiltration and loss of MUC1-C+ tumor cells post CAR-T Infusion Major inclusion criteria Major exclusion criteria 1 3 F Breast (HR+, Her2-) 4 Eribulin MORE 2 4 M Pancreatic 3 FOLFOXIRI LESS • Advanced or metastatic epithelial-derived solid tumor with • No active second primary malignancies DIFFERENTIATED Tumor-infiltrating CAR-T cells CAR-T cells in Blood DIFFERENTIATED measurable disease per RECIST v1.1 • No active autoimmune disease 2 5 F Pancreatic 2 Capecitabine/Radiotherapy • Refractory to standard of care treatment or ineligible/refused • No active systemic infections 2 6 M Prostate 5 Docetaxel 100 90.8% 93.8% 104 3,664 3,792 other existing treatment options • No significant CNS, liver or heart disease T EFF • ANC 1000 /mL, platelets 50,000 /mL, Hb >8 g/dL * Cutoff: 14 Nov 2022 T CM EM Blood SCM Central memory T cell Effector memory T cell Effector T cell ( %) 80 1,718 in • Ferritin 5000 ng/mL. Creatinine 1.5 mg/dL, LFTs 1.5 x ULN Stem cell 103 PATIENT SAFETY, RESPONSE, AND DISPOSITION memory T cell ency 60 STEMNESS MATTERS • Strong correlation with best responses in the clinic u • Self renewing 39.3% ells/ul • More gradual tumor killing with less toxicity 40 • Long lived Products with high % c 102 DOSE ESCALATION AND STUDY SCHEMATIC freq T 38 Safety Response and disposition of T • Better duration of response and potential for re-response L • Multipotent SCM I 20 3.5% T 14 • T engrafts in bone marrow, key to CAR-T success in solid tumors 2.8% Cohort/ Patient Dose-limiting Related Best overall response Days on Status SCM 1 * 0 10 Planned dose escalation CD45+ cell dose # toxicities Grade 3 SAEs (RECIST) study** 0 2 4 6 8 10 12 14 0 2 4 6 8 10 12 14 If the Maximum Tolerated Dose (MTD) has not Days post CAR-T infusion Days post CAR-T infusion 1 None None Progressive disease 178 LTFU Allogeneic platform incorporates learnings from our autologous experience been reached in Arm A following completion of Cohort 4, the dose of P-MUC1C-ALLO1 may be Cohort 1 2 None None Stable disease 121 PTFU Transport Xenograft immunohistochemistry after CAR-T cell infusion 6 0.75 x 106 cells/kg FULLY ALLOGENEIC increased by 5-10 x10 cells/kg for the T-cell isolation Multiplex gene editing to address subsequent dose levels as agreed upon with 3 None None Partial response 102 LTFU Manufacturing graft vs host (safety) and host vs graft (persistence) Leukapheresis Electroporation/ No CAR-T treatment CAR-T Treatment No CAR-T treatment CAR-T Treatment the safety committee and the FDA of allogeneic gene editing 4 None None Stable disease 43 PTFU Healthy product Stain: Anti-Human CD45 Anti-Human CD45 Anti-Human CD8 Anti-Human MUC1 Anti-Human MUC1 CAR-T product donor * Cohort 2 ALLOGENEIC CAR-positive cell Doses are weight-based (cells/kg) * selection and cell 5 None None NE 21 PTFU expansion 2 x 106 cells/kg MHC I knockout Administration TCR knockout Mouse of allogeneic Product testing 6 None None NE* 8 PTFU CAR-T product and release Purification #1 *NE = Not evaluable as subject has not completed D28 DLT assessment or restaging at time of data cutoff; **Days on study defined as days post infusion of P-MUC1C-ALLO1 Patients Cryopreservation Safety Transport Study schematic Every 3 months until month 24, • No dose limiting toxicities or SAEs considered related to P-MUC1C-ALLO1 were observed Enrollment/ P-MUC1-ALL01 Unique allogeneic platform Booster molecule disease progression, and/or new baseline • No CRS, ICANS, or graft vs host disease were observed infusion anticancer treatment • Preserve/improve high T • Robust manufacturing cy/flu SCM Our patented technology is designed to overcome the Mouse • Grade 3-4 treatment-emergent AEs were anemia (n=1), leukopenia (n=1), neutropenia (n=5), lymphocyte count decreased “allo tax” and significantly increase production yield while cy/flu/rit • Optimized dosing regimens • Dramatic cost reductions #2 (n=2) and subclavian vein thrombosis (n=1) • Healthy donor material – Up to 100s of doses preserving desirable T attributes of P-MUC1C-ALLO1 Days -12, -5, -4, -3 Day 0 Days 14, 17, 21, 24, 28 Weeks 5, 6, 8 Months 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 SCM Efficacy • Six heavily pretreated patients have been dosed with P-MUC1C-ALLO1. Among the 4 evaluable patients, 1 had best overall response —Maximum tumor infiltration at 10 days post CAR-T infusion resulting in >90% of cells in tumor mass at day 10 are CAR-T (TIL) of PR and 1 had SD at the low starting dose of 0.75 x 106 cells/kg and additionally one subject had SD at the 2 x 106 cells/kg dose MUC1-C is a truncated form of MUC1 enriched in many epithelial-derived carcinomas—TIL at day 10 are more differentiated Tem, while reservoir of TSCM / TCM resides in bone marrow—Data previously presented on Poseida’s P-PSMA-101 show CAR-T bone trophic activity in mCRPC in which a biopsy of prior bone Screening Conditioning Post-treatment follow-up visits Long-term metastasis showed CAR-T cells, bone remodeling, and bone marrow but no tumor cells5 chemotherapy follow-up CONCLUSIONS P-MUC1C-ALLO1 epitope highly prevalent in solid tumor indications P-MUC1C-ALLO1 MANUFACTURING CHARACTERISTICS • P-MUC1C-ALLO1 is largely comprised of early memory T cells, i.e., TSCM and TCM Tumor tissue arrays* • The Phase 1 trial for P-MUC1C-ALLO1 was initiated in May 2022 and is estimated to treat up to 100 patients 5 3 2 across 15 sites 100 • A high percentage of tumor samples tested positive for • P-MUC1C-ALLO1 is largely comprised of 10562 135 Mean (Range) Clinical Lots (n = 6) 82 42 staining with scFv binder used by P-MUC1C-ALLO1 CAR early memory T cells, i.e., T and T • Three patients have been treated with P-MUC1C-ALLO1 in cohort 1 and 3 patients in cohort 2 80 4 4 SCM CM – ~90% of breast and colon tumors were positive, as were CD4/CD8 Ratio 0.9 (0.3, 2.0) (CD45RO-CD45RA+CD62L+ or • Both cohort 1 and cohort 2 were completed without dose-limiting toxicities, CRS or graft vs host disease 5 60 88% of ovary, 81% of lung, and 81% of renal tumors positivity Stem cell memory CD8 T cells, % 54.8 (32.9, 79.9) CD45RO+CD45RA-CD62L+, respectively) observed staining 40 • Expression profile was consistent with what has been widely of Central memory CD8 T cells, % 44.4 (19.2, 66.7) • Low composition of late memory T cells • Early signs of clinical activity were observed including 1 partial response in a breast cancer patient at the low 5 5 reported for full-length MUC1 % 20 dose and two other patients with gastrointestinal malignancies achieving stable disease MUC1 is overexpressed in many cancers. Other tumor-specific features of MUC1 include: Effector memory CD8 T cells, % 0.6 (0.2, 1.8) (<5%) 0 2 4 2 1. MUC1 is normally expressed on apical surface of epithelium, but globally on all surfaces of cancer cells due to loss of cell polarity Effector CD8 T cells, % 0.2 (0, 0.6) • P-MUC1C-ALLO1 Phase 1 trial enrollment and dose escalation is on-going with subjects now enrolling in • Products are consistently >90% CCR7+ 2. MUC1 is hypoglycosylated on tumor cells cohort 3 dose-level (Arm A) and cyclic dosing (Arm B). Additionally, previously treated subjects are eligible % CCR7 + 95.0 (94.0, 95.8) 3. Increased shedding of MUC1-N due to proteases in the tumor microenvironment, producing high levels of monomeric MUC1-C • Reliably high frequency of CAR+ cells *Numbers above bar indicate number of samples analyzed per protocol for re-treatment at the original dose given or at a higher dose-level that has cleared DLT period 4. The presence of cryptic epitopes on MUC1-C in the tumor microenvironment, hypothesized to be the result of proteolysis % CAR + 98.3 (96.7, 98.9) (>95%) across clinical lots Disclosures: The presenter has the following relevant financial and non-financial relationships to disclose: Financial Interests relating to Research Support: Merck Sharp and Dohme, PACT Pharma, ABBREVIATIONS: AE = adverse event; ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; BLI = bioluminescent imaging; CNS = central nervous system; CRS = cytokine release syndrome; CTC = circulating tumor cells; DOR = duration of response; Hb = hemoglobin; REFERENCES: 1. Taylor-Papadimitriou J et al. Biochem Soc Trans. 2018;46(3):659-668. 2. Gutierrez R et al. J Clin Oncol. 2021;39(suppl 15). Abstract. Poseida Therapeutics, TCR2 Therapeutics, Roche/Genentech, Nutcracker Therapeutics, Regents of the University of California; Financial Interests relating to Travel/Accommodations: Roche/Genentech HLH = hemophagocytic lymphohistiocytosis; ICANS = immune effector cell–associated neurotoxicity; LTFU = long-term follow-up; LVEF = left ventricular ejection fraction; MAS = macrophage activation syndrome; MTD = maximum tolerated dose; ORR = overall response rate; OS = overall survival; PBS = phosphate-buffered saline; 3. Specht J et al. J Clin Oncol. 2021;39(suppl 15). Abstract. 4. Lee DW et al. Biol Blood Marrow Transplant. 2019:25(4):625-638. 5. Slovin S et al. ASCO GU 2022 Presenting author: David.Oh@ucsf.edu PFS = progression-free survival; PTFU = post-treatment follow-up; Q2W, every 2 weeks; RECIST = Response Evaluation Criteria in Solid Tumors; RP2D = recommended Phase 2 dose; SAD = single ascending dose; TTR = time to response; ULN = upper limit of normal. Clinical trial identifier: NCT05239143 ACKNOWLEDGMENTS: The authors and Poseida Therapeutics, Inc., thank the patients, caregivers, investigators, and study site staff for their involvement in this Study sponsored by Poseida Therapeutics study. This study was funded by Poseida (San Diego, CA).
Exhibit 99.3
47P—Phase I Study to Assess the Safety and Efficacy of P-BCMA-ALLO1, a Fully Allogeneic CAR T Therapy, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM) Mehmet Kocoglu,1 Adam Asch,2 Aravind Ramakrishnan,3 Carlos Bachier,4 Thomas Martin III,5 Tulio Rodriguez,6 Katherine McArthur,7 Joanne McCaigue,7 Christopher E. Martin,7 Maggie Zhang,7 Hamid Namini ,7 Eric Ostertag,7 Matthew A. Spear,8 Ellen Christie,7 Rajesh Belani,7 Stacey Cranert,7 Julia Coronella,7 Devon J. Shedlock,7 Caitlin Costello,9 1University of Maryland Greenebaum Cancer Center, Baltimore, MD; 2Stephenson Cancer Center, Oklahoma University, Oklahoma City, OK; 3Sarah Cannon Transplant and Cellular Therapy Program at St. David’s South Austin Medical Center, Austin, TX; 4Sarah Cannon Transplant and Cellular Therapy Program at Methodist Hospital, San Antonio, TX; 5UCSF Medical Center at Parnassus, San Francisco, CA; 6Bone Marrow Transplantation, Advocate Lutheran General Hospital, Park Ridge, IL; 7Poseida Therapeutics, Inc., San Diego, CA; 8Denovo Biopharma, San Diego, CA; 9UCSD Moores Cancer Center, La Jolla, CA BACKGROUND CLINICAL STUDY METHODS AND DESIGN PHASE 1 DOSE-ESCALATION CLINICAL RESULTS EFFICACY RESULTS • Multiple myeloma (MM) is an incurable plasma cell malignancy with high expression of B-cell Maturation Topic Detail PATIENT DEMOGRAPHICS AND CHARACTERISTICS Antigen (BCMA) • Open label, multicenter, Phase 1, dose escalation study to assess the safety and efficacy of P-Autologous Chimeric Antigen Receptor T-cell (CAR T) therapies targeting BCMA have shown significant activity Study information BCMA-ALLO1, which will be administered intravenously as a single dose. Dose levels will be in MM tested in 3+3 escalation design in approximately 40 RRMM patients • Unfortunately, autologous CAR T poses several challenges including the need for apheresis, long manufacturing Dose escalation: Standard 3+3 design is utilized in the dose-escalating cohorts to evaluate times, high manufacturing costs, costs and poor product quality because the T-cells are obtained from DLTs within 28 days post P-BCMA-ALLO1 administration. Adverse events (AE), Serious myeloma patients Adverse Events (SAE) and Treatment Emergent Adverse Events (TEAEs) will be evaluated • An allogeneic “off the shelf” CAR T could address these unmet needs by eliminating the need for apheresis, throughout the study. providing on demand therapy and better-quality T-cells from healthy donors for manufacturing Study design If cohort 5 is completed without a Maximum Tolerated Dose (MTD), the Safety Committee • P-BCMA-ALLO1 is an allogeneic CAR T targeting BCMA being investigated for the treatment of relapsed may elect to assess further escalation cohorts in higher dose levels. refractory multiple myeloma (RRMM) P-BCMA-ALLO1 will be administered on D0 following lymphodepleting chemotherapy: 2 2 • P-BCMA-ALLO1 utilizes non-viral transposon-based integration (piggyBac® DNA Delivery System) that Fludarabine 30 mg/m /day and cyclophosphamide 300 mg/m /day on D-5, -4, -3 introduces a humanized anti-BCMA VH-based CAR producing a highly enriched T stem cell memory (TSCM) RRMM patients who have received greater than 3 lines of therapy, which must include a Study patient product proteasome inhibitor (PI), immunomodulatory drug (IMiDs) and CD38 monoclonal antibody population • The Cas-CLOVER™ Site-Specific Gene Editing System eliminates endogenous T cell receptor (TCR) expression (mAb) via knockout of the TCR beta chain 1 gene to prevent graft-vs-host disease and reduces MHC class I expression Safety/feasibility: AE, Cytokine Release Syndrome (CRS), neurotoxicity, Graft vs Host Disease to eliminate host-vs-graft responses via beta-2 microglobulin gene knockout Evaluation criteria: (GVHD) efficacy, safety, and Efficacy: IMWG criteria will be used for response. Overall Response Rate (ORR), Time to • P-BCMA-ALLO1 demonstrated compelling activity in MM xenografts, providing rationale for this first-in-human other variables Response (TTR), Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival phase I study (OS) will be analyzed. CAS-CLOVER: CLEAN GENE EDITING P-BCMA-ALLO1 cellular kinetics; T cell composition in P-BCMA-ALLO1 drug product; immune Exploratory response in the context of patient-donor match metrics; soluble BCMA levels; BCMA expression on MM cells; putative blood markers of safety and efficacy. Major Inclusion Criteria Major Exclusion Criteria • Relapsed / Refractory Multiple Myeloma as defined by • Active hemolytic anemia; plasma cell leukemia, etc. the IMWG • Active second malignancies other than multiple SAFETY RESULTS • Must have received at least three lines of therapy that myeloma must include a PI, IMiDs and CD38 mAb • Active autoimmune disease • Have a measurable disease as defined by one of the • History of significant central nervous system disease following: 1) serum M-protein > 1.0g/dL; 2) Urine M-protein > 200mg/24hr; 3) FLC > 10 mg/dL; 4) Bone • Active systemic infections marrow plasma cells > 30% • History of hepatitis; HTLV or HIV infection • ANC ≥1000 /mL, platelets 50,000 /mL, Hb >8 g/dL SUMMARY • Has NYHA Class III or IV heart failure • Creatinine ≤1.5 mg/dL, SGOT < 3x ULN • Received prior gene therapy All enrolled patients are heavily treated having received 6.5 median prior lines of • therapy ALLOGENEIC PLATFORM • LVEF ≥45% • 3 out of 6 evaluable cohort 1 patients had received prior BCMA targeted therapy Transport FULLY ALLOGENEIC T-cell isolation Multiplex gene editing to address DOSE ESCALATION PLAN AND STUDY SCHEMATIC • 4 out of 6 evaluable cohort 1 patients had high risk cytogenetics Manufacturing graft vs host (safety) and host vs graft (persistence) Leukapheresis Electroporation/ of allogeneic gene editing Healthy product CAR-T product • ORR for Cohort 1 is 50% donor ALLOGENEIC Single infusion CAR-positive cell Dose Levels (cells/kg/dose) include: selection and cell If cohort 5 is completed without expansion 6 Administration MHC I knockout Cohort minus 2: 0.0625 x 10 • ORR in patients who have received prior BCMA targeting therapy is 66% TCR knockout concluding an MTD, the safety of allogeneic Product testing Purification Cohort minus 1: 0.25 x 106 CAR-T product and release Committee may elect to assess Cohort 1: 0.75 x 106 • ORR in patients with high-risk cytogenetics is 50% Patients Cryopreservation further escalation cohorts in 5-10 Transport Cohort 2: 2 x 106 6 X 106 P-BCMA-ALLO1 cells/kg Cohort 3: 6 x 10 Unique allogeneic platform Booster molecule Cohort 4: 10 x 106 increments. • Preserve/improve high TSCM • Robust manufacturing Our patented technology is designed to overcome the 6 “allo tax” and significantly increase production yield while Cohort 5: 15 x 10 • Optimized dosing regimens • Dramatic cost reductions CONCLUSION – Up to 100s of doses preserving desirable TSCM attributes of P-MUC1C-ALLO1 • Healthy donor material SUMMARY • P-BCMA-ALLO1 is an allogeneic “off the shelf” BCMA targeting CAR T therapy that CAR Disease assessments at Weeks 2,3,4,6 and 8 and Months T 3, 4, 5, 6, 7, 8, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and demonstrates compelling anti-myeloma activity, in a heavily pretreated patient population, at—every 6 months until disease progression the lowest dose tested, while demonstrating excellent tolerability PRECLINICAL RESULTS Cell • A total of 10 patients were treated with P-BCMA-ALLO1, 7 in cohort 1, and 3 in cohort 2 Enrollment • It is active in patients who have failed prior BCMA targeted therapy and in patients with high-Efficacy in the RPMI-8226 Multiple Myeloma Model • Three SAE occurred in cohort 1 (G3 Febrile Neutropenia, G3 Disseminated Herpes Zoster, Eligibility Long Term Follow-Up yearly risk myeloma Lymphodepletion Infusion Post treatment Follow-Up Visits G3 Cryptosporidiosis infection) for up to 15 Years post dosing 2,000 • The clinical activity is seen without CRS, GVHD or neurotoxicity No CAR T 3 ] Tumor implant: RPMI-8226, 107 cells s.c. • No SAE were related to P-BCMA-ALLO1 m 1,500 Auto • P-BCMA-ALLO1 represents an important cellular therapy advance and could represent an [ m Allo 1 P-BCMA-ALLO1 infusion: 5 x 106 Allo 2 • No CRS, GVHD, neurotoxicity, DLT or Adverse Events of Special Interest (AESI) have been attractive treatment option for multiple myeloma cells on D0 1,000 Allo 3 NSG Volume Day Day Day Weeks Months Every 3 Months to 3 years then every Allo 4 observed as of the data cutoff r • Dose escalation is ongoing o 500 Allo 5 -5, -4, -3 0 1, 4, 7, 10 2, 3, 4, 6, 8 3, 6, 9, 12, 15, 18 6 Months until disease Progression Tum Allo1-6 indicate lots from • Six cohort 1 patients are available for response evaluation • Additional treatment regimens including cyclic dosing, repeat dosing, Rituximab combination 0 each of 6 individual healthy -7 0 49 Inpatient and fixed (non-weight based) dosing will be explored 0 7 14 21 28 35 42 49 donors Outpatient Days post CAR-T infusion N = 4 mice / group (until day 7) Error bars = SEM Disclosures: The presenter has the following relevant financial and non-financial relationships to disclose: Financial Interests relating to research Support: Poseida Therapeutics ACKNOWLEDGMENTS: The authors and Poseida Therapeutics, Inc., thank the patients, caregivers, investigators, and study site staff for their Presenting author: mkocoglu@umm.edu Clinical trial identifier: NCT04960579 involvement in this study. This study was sponsored and funded by Poseida Therapeutics (San Diego, CA).