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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported):

November 14, 2024

 

 

Poseida Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-39376   47-2846548

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

 

9390 Towne Centre Drive, Suite 200  
San Diego, California   92121
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code: (858) 779-3100

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
Symbol(s)

 

Name of each exchange

on which registered

Common Stock, par value $0.0001 per share   PSTX   Nasdaq Global Select Market

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 November 14, 2024, Poseida Therapeutics, Inc. (the “Company”) issued a press release announcing that members of its management are providing an update on the Company’s cell therapy research and development programs and making available a corporate presentation. A copy of the press release and the corporate presentation are attached as Exhibit 99.1 and Exhibit 99.2, respectively, to this report. The corporate presentation will also be available under the “Investors & Media” section of the Company’s website.

The information in this Item 7.01 of this report (including Exhibits 99.1 and 99.2) 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.

 

Exhibit

No.

   Description
99.1    Press Release, dated November 14, 2024
99.2    Corporate Presentation, dated November 14, 2024
104    Cover Page Interactive Data File

 


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: November 14, 2024     By:  

/s/ Harry J. Leonhardt, Esq.

    Name:   Harry J. Leonhardt, Esq.
    Title:   General Counsel, Chief Compliance Officer & Corporate Secretary

Exhibit 99.1

 

LOGO

 

Poseida Therapeutics Hosts Cell Therapy R&D Day Highlighting Its Innovative Clinical and Preclinical Pipeline

Emerging leadership in allogeneic CAR-T for hematologic malignancies demonstrated by recent P-BCMA-ALLO1 Phase 1 data and new preclinical findings for P-CD19CD20-ALLO1 and P-CD70-ALLO1

Latest preclinical data on P-BCMACD19-ALLO1 demonstrates its potential as a next-generation allogeneic TSCM-rich CAR-T for both autoimmune diseases and oncology

Advancing innovative strategies to overcome the unique challenges of applying CAR-T to solid tumors

Virtual R&D Day featuring partner Astellas Pharma and Poseida’s leadership and scientific teams to be held today at 10:00am ET / 7:00am PT

SAN DIEGO, November 14, 2024  Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune and rare diseases, today announced plans to share progress across its clinical- and earlier-stage pipeline of differentiated T stem cell memory cells (TSCM)-rich allogeneic CAR-T therapies in oncology and autoimmune diseases during a virtual R&D Day to be held today at 10:00am ET /7:00am PT.

“We believe Poseida is well positioned to be a cell therapy leader based on the unique capabilities of our proprietary non-viral technology platform and our allogeneic TSCM-rich CAR-T approach,” said Kristin Yarema, Ph.D., President and Chief Executive Officer of Poseida Therapeutics. “We are organizing our pipeline around three pillars – hematologic malignancies, solid tumors and autoimmune diseases – with multiple candidates in each that give us a wide range of opportunities. In the emerging field of cell therapy for autoimmune diseases, we are optimistic that our platform can build upon the early success seen with autologous CAR-T by offering an off-the-shelf option that would expand accessibility and address the potential drivers of relapse with more complete B cell depletion.”

“Building on the advantages of our non-viral allogeneic TSCM-rich approach, we are implementing several advanced technologies aimed at bringing the benefits of CAR-T therapy to patients with solid tumors,” said Devon J. Shedlock, Ph.D., Chief Scientific Officer, Cell Therapy at Poseida Therapeutics. “This includes our collaboration with Astellas, which brings together the unique technologies from both companies to create a new class of CAR-T, convertibleCARs®, which employs multi-antigen targeting and other enhancements to improve CAR-T potency and persistence.”

The event will feature presentations by members of Poseida’s management team and will include a fireside chat with Peter Sandor, M.D., EVP and Head of Corporate Strategy at Astellas Pharma, that will cover the research collaboration and license agreement between Xyphos Biosciences, Inc., (a wholly owned subsidiary of Astellas, “Xyphos”) and Poseida to develop novel convertibleCAR® programs by combining the innovative cell therapy platforms from each of the companies. Poseida management will participate in a Q&A session at the end of the program.


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Cell therapy technology platform: Poseida has built a full set of non-viral capabilities to design and develop allogeneic, TSCM-rich CAR-T therapies. TSCM cells are considered ideal for CAR-T therapy because they are long-lived, multi-potent and self-replicating, with the potential for an improved safety and efficacy profile. This compares to other approaches, which either use a different cell type or drive T cell differentiation (and therefore less stemness) as part of the process to manufacture the CAR-T cells. The key elements of Poseida’s approach include:

 

   

Non-viral, transposon-based gene insertion system preferentially integrates genes into naïve and TSCM cells, with a high cargo capacity that allows for adding multiple genes to enhance functionality and add safety features

 

   

Cas-CLOVER gene editing system preserves the TSCM cell type and operates effectively in resting T cells. It offers approximately 25-times greater fidelity than CRISPR-Cas9, supporting improved safety and quality

 

   

Wholly-owned, onsite GMP manufacturing facility positioned to serve discovery through commercial needs across the Company’s pipeline. The Company’s Booster Molecule has enabled a scalable, lower cost manufacturing approach with the proven ability to generate cell yield up to over 100 doses per batch

Emerging leadership in allogeneic CAR-T for hematologic malignancies: Poseida will provide an overview of recently reported interim Phase 1 results for P-BCMA-ALLO1, its lead CAR-T program targeting BCMA for the treatment of multiple myeloma. New preclinical data suggest that P-BCMA-ALLO1 effectively targets mutations that are known to arise in patients with relapse after prior anti-BCMA therapies. P-BCMA-ALLO1 is part of Poseida’s collaboration with Roche and is currently enrolling a Phase 1b dose expansion study, which will be outlined in the presentation. In addition, the Company will highlight its emerging pipeline programs for hematologic malignancies:

 

   

P-CD19CD20-ALLO1 is the Company’s first dual CAR-T program targeting CD19 and CD20 for the treatment of B-cell malignancies in collaboration with Roche. New preclinical data demonstrate that P-CD19CD20-ALLO1 delivers high in vitro potency and strong in vivo antitumor activity for either CD19 or CD20 single-positive target cells, as well as double-positive targets. A Phase 1 clinical trial is enrolling patients with selected B-cell malignancies, with initial clinical data anticipated in 2025. Additional information about the trial is available at www.clinicaltrials.gov using identifier: NCT06014762.

 

   

Beyond hematologic malignancies, preclinical data also demonstrate robust in vitro activity against patient-derived B cells across multiple autoimmune diseases

 

   

P-CD70-ALLO1 is a preclinical program targeting CD70 for the treatment of diseases including acute myeloid leukemia (AML). New preclinical data demonstrate P-CD70-ALLO1’s robust anti-AML effect, with no toxicity to hematopoietic stem cells. In addition, there is a growing body of clinical and preclinical evidence that targeting CD70 with cell therapy may be an effective treatment for solid tumors. Roche has an option to add this as a potential new program to the collaboration

Expanding allogeneic TSCM-rich CAR-T to autoimmune disease: Poseida’s cell therapy technology platform has the potential to create CAR-T therapies designed to address the challenges with existing emerging approaches to applying cell therapy to autoimmune disease, including autologous CAR-T, in vivo CAR-T and T cell engagers. The Company’s lead program for autoimmune disease is P-BCMACD19-ALLO1, a dual CAR-T targeting BCMA and CD19. New preclinical data demonstrate P-BCMACD19-ALLO1’s potential in both autoimmune disease and oncology:

 

   

Demonstrated robust in vitro killing of patient-derived B cells across multiple autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and multiple sclerosis (MS), which collectively affect more than 5 million people in the U.S.


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Achieved dose-dependent depletion of primary human B cells in a humanized mouse model generated with human CD34+ cells

 

   

Effectively eliminated primary human CD81+CD19+ multiple myeloma progenitor cells from patient bone marrow samples, addressing cells associated with relapse where BCMA-only targeted therapies were ineffective

 

   

Demonstrated ability of P-BCMACD19-ALLO1 and P-BCMA-ALLO1 to kill tumor cells expressing known mutant forms of BCMA, which are linked to relapse in patients treated with autologous CAR-T and bispecific T cell engager therapies directed at BCMA

Poseida is conducting IND-enabling studies for P-BCMACD19-ALLO1 and plans to file one or more INDs for an autoimmune disease indication with the U.S. Food and Drug Administration.

Addressing historical barriers for CAR-T in solid tumors through a broad array of bold, innovative technologies enabled by the Company’s platform: There are currently no CAR-T therapies approved for solid tumors, with several key factors believed to be roadblocks: 1) antigen heterogeneity; 2) differing lymphodepletion needs compared to hematologic malignancies to enable CAR-T cell engraftment, tracking, and infiltration; 3) on-target off-tumor toxicity; and 4) hostile tumor microenvironment. Poseida is approaching these challenges with a suite of technologies across multiple solid tumor programs:

 

   

P-MUC1C-ALLO1 is Poseida’s lead solid tumor CAR-T program targeting MUC1-C, a membrane protein overexpressed in many epithelial cancers. A Phase 1 clinical trial is enrolling patients with treatment-resistant breast, ovarian, colorectal and other solid tumors, with ongoing exploration of P-MUC1C-ALLO1 dosing and lymphodepletion regimens. A clinical data update is planned for the European Society for Medical Oncology Immuno-Oncology Congress 2024 (ESMO-IO) taking place in Geneva December 11-13, 2024. A patient case study from the Phase 1 trial demonstrated a 42% decrease in paraesophageal lymph node size with prolonged stable disease for nearly a year in a heavily pretreated appendiceal carcinoma patient. New preclinical data suggest adding low-dose methotrexate to standard lymphodepletion may enhance CAR-T expansion and persistence

 

   

P-PSMA-ALLO1 is a preclinical program targeting PSMA for prostate cancer. In preclinical models, P-PSMA-ALLO1’s dual CAR format showed superior in vivo anti-tumor activity and cytotoxicity compared to single and tandem binder CAR-Ts

 

   

Poseida and Xyphos are developing allogeneic convertibleCARs® for solid tumors, combining Poseida’s allogeneic CAR-TSCM platform with Xyphos’ ACCEL technology to create controlled, long lasting, and highly active CAR-T therapies. New preclinical data shows positive results for an allogeneic convertibleCAR-TSCM targeting universal inert natural killer group 2 member D receptor (iNKG2D), paired with a solid tumor antigen-targeting MicAbody. Poseida and Xyphos are working to optimize this convertibleCAR® and MicAbody pairing, and other platform technologies designed to maximize potency and persistence

 

   

Poseida will highlight its allogeneic CAR-TCR-T cells to address antigen heterogeneity in solid tumors. The Company recently presented new preclinical data demonstrating enhanced potency to better target solid tumors at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting. Preclinical data highlight the potential of a combination of CAR-TCR-T cell treatment followed by a T cell engager (TCE). In this model, MUC1C-CAR and NY-ESO-1-TCR T cells effectively controlled a primary tumor (MUC1C+/NY-ESO-1+/CD70-), and later were reactivated and re-directed by a CD70 TCE to control challenge by a secondary tumor (MUC1C-/NY-ESO-1-/CD70+)


LOGO

 

In-house manufacturing to support Poseida’s broad cell therapy pipeline: the Company will highlight the capabilities of its GMP facility and team, including:

 

   

New data demonstrated high-purity apheresis across different healthy donors, with consistency in CAR-T manufacturing (cellular expansion, gene editing, final phenotype) across collections from the same donor

 

   

Future manufacturing platform enhancement opportunities including AI-assisted donor screening to improve efficiency; improving electroporation unit operations to improve gene editing efficiency and subsequent cell health; and leveraging dynamic bioreactor environments to increase yields

Video Webcast and Replay

This virtual event and access to the live webcast is available through the following registration link: https://wsw.com/webcast/cc/pstx7/1467684.

Registration for this virtual event and access to a replay of the live webcast will be available on the Investors & Media section of www.poseida.com. A replay of the webcast will be available for approximately 90 days following the presentation.

About Poseida Therapeutics, Inc.

Poseida Therapeutics is a clinical-stage biopharmaceutical company advancing differentiated allogeneic cell therapies and genetic medicines with the capacity to cure. The Company’s pipeline includes investigational allogeneic CAR-T cell therapies for hematologic cancers, autoimmune diseases, and solid tumors, as well as investigational in vivo genetic medicines that address patient populations with high unmet medical need. The Company’s approach is based on its proprietary genetic editing platforms, including its non-viral transposon-based DNA delivery system, Cas-CLOVER Site-Specific Gene Editing System, Booster Molecule and nanoparticle gene delivery technologies, as well as in-house GMP cell therapy manufacturing. The Company has formed strategic collaborations with Roche and Astellas to unlock the promise of cell therapies for cancer patients. Learn more at www.poseida.com and connect with Poseida on X 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; anticipated timelines and milestones with respect to the Company’s development programs and manufacturing activities and capabilities; the potential capabilities and benefits of the Company’s technology platforms and product candidates, including the efficacy and safety profile of such product candidates; the quotes from Drs. Yarema and Shedlock; and the Company’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 the Company’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, the fact that interim data from the Company’s clinical trials may change as more patient data become available and remain subject to audit and verification procedures that could result in


LOGO

 

material differences from the final data; the Company’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; the Company’s ability to retain key scientific or management personnel; the Company’s ongoing and planned clinical trials; risks and uncertainties associated with conducting clinical trials; competition in the Company’s target markets; whether any of the Company’s product candidates will be shown to be effective or safe; the Company’s ability to finance continued operations; the fact that the Company will have limited control over the efforts and resources that its collaborators devote to advancing development programs under their respective collaboration agreements; the fact that the Company may not receive the potential fees, reimbursements and payments under the collaboration agreements; the ability of the Company’s collaborators to early terminate the collaboration, such that the Company may not fully realize the benefits of the collaborations; and the other risks and uncertainties described in the Company’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. The Company 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.

###

Poseida Investor and Media Relations:

Alex Chapman

Senior Vice President, IR & Corporate Communications

IR@poseida.com

Sarah Thailing

Senior Director, IR & Corporate Communications

PR@poseida.com

Exhibit 99.2 Cell Therapy R&D Day Differentiated Allogeneic Cell Therapies in Oncology and Autoimmune Disease NOVEMBER 14, 2024


Disclaimer This presentation and any accompanying oral commentary contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts and include, without limitation, statements related to future events; our future financial performance or condition; business strategy; expected timing and plans with respect to development milestones, clinical trials, and regulatory and manufacturing activities; estimated market opportunities for product candidates; potential capabilities and benefits of our technology platforms and product candidates, including the efficacy, tolerability and safety profile of such product candidates; the quotes from Drs. Dholaria and Martin; our plans and strategy with respect to developing our technologies and product candidates; our ability to exploit and consummate additional business development opportunities; statements regarding the upfront payment and other potential fees, milestone and royalty payments we may receive pursuant to our collaboration agreements and research and development activities under our collaboration agreements; and future results of anticipated development efforts. Words such as “expect(s),” “feel(s),” “believe(s),” “will,” “may,” “anticipate(s)”, “potentially” or negative of these terms or similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on management's current expectations of future events only as of the date of this presentation and are subject to a number of important risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the fact that interim data from the Company’s clinical trials may change as more patient data become available and remain subject to audit and verification procedures that could result in material differences from the final data; our ongoing and planned clinical trials; the fact that our collaboration agreements may be terminated early such that we may not fully realize the benefits of such collaborations; the fact that we will have limited control over the efforts and resources our collaborators devote to advancing development programs under our collaboration agreements and we may not receive the potential fees, reimbursements and payments under our collaboration agreements; risks and uncertainties associated with conducting clinical trials; whether any of our product candidates will be shown to be safe and effective; our ability to finance continued operations; our reliance on third parties for various aspects of our business; competition in our target markets; our ability to protect our intellectual property; our ability to retain key scientific or management personnel; risks and uncertainties associated with development and regulatory approval of novel product candidates in the biopharmaceutical industry; and other risks and uncertainties described in our filings with the Securities and Exchange Commission, including under the heading “Risk Factors”. Except as required by law, we assume no obligation to update these forward-looking statements, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. 2 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Introduction: Poseida poised to lead in allogeneic cell therapy Kristin Yarema, PhD President & CEO


Introduction: Poseida poised to lead in allogeneic cell therapy Kristin Yarema, PhD Heme malignancies: P-BCMA-ALLO1 leads a portfolio of allogeneic T -rich CAR-T programs SCM Syed Rizvi, MD From hematology to autoimmune disease: Poseida’s BCMA-CD19 dual CAR-T Kurinji Pandiyan, PhD Waves of innovation in solid tumor cell therapy Devon J. Shedlock, PhD The power of partnerships fireside chat Peter Sandor, MD (Astellas) & Karen Basbaum In-house GMP manufacturing capabilities Loren Wagner Concluding remarks Kristin Yarema, PhD Q&A Executive and Scientific Leadership 4 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


On a mission to advance a new class of cell therapies & genetic medicines GENETIC MEDICINES ALLOGENEIC CAR-T Non-viral delivery for gene Enabling broad and rapid “Top 10 Public Gene Therapy insertion and gene editing patient access to Company” to meet patient needs transformational CAR-T “Top 10 Public Gene Editing Company” UNMATCHED PLATFORM Innovating with powerful, proprietary, and differentiated genetic engineering technologies © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Our unique system of non-viral tools can be used individually or together – with the capacity to treat cancer, autoimmune and rare diseases POSEIDA SYSTEM OF NON-VIRAL TOOLS + Cas-CLOVER Transposon-based Enabling Gene Editing DNA insertion technologies NON-VIRAL GENETIC MEDICINES ALLOGENEIC CAR-T Non-viral, in vivo editing of Dual targeting disease-relevant gene using MHC I KO Cas-CLOVER transposon-based gene insertion Healthy TCR KO Donor T Cells Cas-CLOVER gene editing Whole gene insertion via non- viral transposon for functional T -rich CAR-T cells SCM correction 6 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Poseida’s robust platform underpins and enables work in three cell therapy areas Areas of unmet need poised for disruption with the right allogeneic CAR-T platform Opportunity Hematology 200K New U.S. patients per year, Despite auto CAR-T approvals, access heavily representing ~10% of all new restricted with safety issues further compounding 1,2 cancer incidences need for novel safe & efficacious options POSEIDA’S VISION: Our T -rich allogeneic SCM Solid Tumor CAR-T will enable all Significant unmet need, historically elusive to 1,2 New U.S. patients per year 2M+ patients who can benefit CAR-T, requiring novel, innovative approaches from transformational for success cell therapy to do so Autoimmune Disease U.S. patients living with MS, Exciting potential for CAR-Ts to deliver “immune RA, and Lupus, which are 5M+ reset” across a broad range of diseases, with the 3,4 increasing in prevalence right allo platform crucial to unlock opportunity Note: size of circles not to scale 1. Cancer Facts & Figures 2024, American Cancer Society. 2. Cancer Statistics 2024, National Cancer Institute. 3. National MS Society, Arthritis.org, CDC. 4. Miller FW. Curr Opin Immunol. 2023 Feb;80:102266. 7 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Poseida has built a full set of capabilities needed for success in allogeneic cell therapy OTHERS POSEIDA SYSTEM POSEIDA ADVANTAGE • Product profile unique in • Differentiated T cells • T stem cell memory cells 'stemness’ CELL TYPE • Variety of other immune (T ) SCM • Expected better safety cell types • Persistent, self-renewing cells • Safety GENE INSERTION • Viruses • Nonviral transposon • Product purity (add CAR) • (single-gene capacity) (multigene capacity) • Multi-CAR products • Maintains T type SCM • Safety, quality GENE EDITING • Older technologies with • Cas-CLOVER, high- • Maintains T type lower fidelity* fidelity (for alloreactivity) SCM • Wholly-owned onsite • Proven CMC capability (up to • Often outsourced SCALABLE GMP facility over 100 doses/batch yields) • Challenging to reach MANUFACTURING • Booster molecule- • Scalable, lower cost high yields enabled yield *E.g., TALEN, Cas9 8 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. CMC, Chemistry, manufacturing and controls; GMP, good manufacturing practice.


Our unique and proprietary toolkit has the capabilities required to produce T -rich SCM allogeneic CAR-T, with potential to drive depth and durability of response Fully Non-Viral Approach Transposon Quality Enabling Tech Cas-CLOVER 1 2 3 Non-viral gene Gene editing manufacturing at insertion system system scale ✓ Preferentially insert into T ✓ Preserve T cell type✓ Preserve T cell type SCM SCM SCM High yield at low cost High cargo capacity enhances Designed to address GVH & functionality HVG alloreactivity Pure CAR-T cell product Allows inclusion of multiple safety ~25x greater fidelity vs. CRISPR- Stored in inventory and ready features + functionality Cas9 for use Poseida IP-protected tools designed to work together as a system T correlates with depth and durability of response SCM GVH, graft-versus-host; HVG, host-versus-graft 9 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Our rich pipeline includes partnered and wholly-owned allogeneic CAR-T as well as non-viral genetic medicines INDICATION PRECLINICAL IND-ENABLING PHASE 1 PHASE 2 Heme Malignancies and Autoimmune Diseases Multiple myeloma P-BCMA-ALLO1 B-cell malignancies P-CD19CD20-ALLO1 Multiple myeloma and P-BCMACD19-ALLO1 autoimmune diseases Option P-CD70-ALLO1 Acute myeloid leukemia Allogeneic CAR-T Heme malignancies, including Novel Dual CAR multiple myeloma Solid Tumor* Breast, ovarian, colorectal, P-MUC1C-ALLO1 lung, pancreatic, renal Prostate cancer P-PSMA-ALLO1 ® ConvertibleCAR x2 Solid tumor programs* Liver Directed Hereditary Angioedema (HAE) Genetic P-KLKB1-101 Medicines Hemophilia A P-FVIII-101 10 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. *Solid tumor targets identified in conjunction with the research collaboration and license agreement with Astellas are yet to be disclosed


Poseida’s path to value creation in allogeneic cell therapy Presently heading into our second growth horizon Disrupt Cell Extend Therapy Approach Build Foundation DELIVER FOR PATIENTS DRIVE VALUE • Stream assets from allogeneic CAR- VALIDATE PLATFORM T product engine SCM • Enter autoimmune disease space • Advance non-viral allogenic CAR- • Launch new cell therapy platforms • Deepen and extend pharma T assets in the clinic for greater reach (CAR-TCR and SCM partnerships beyond) ― P-BCMA-ALLO1 in Phase 1b; • Grow wholly-owned asset pipeline RMAT designation • Manufacture high volume, low • Refine next-generation tools & COGS products at scale ― 3 clinical stage programs technologies across liquid & solid tumors • Commercialize partnered and own • Further strengthen manufacturing, assets that have strong value • Establish partnerships with Roche healthy donor competencies propositions and Astellas • Manufacture GMP product in-house 11 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Heme malignancies: P-BCMA-ALLO1 leads a portfolio of allogeneic T -rich CAR-T programs SCM Syed Rizvi, MD Chief Medical Officer


Right off the bat, I was very impressed with the “ rapid responses we saw in a couple of initial patients we treated, including several patients of my colleagues who had failed other standard therapies, including a significant amount of extramedullary disease. And within 4 to 6 weeks, the disease melted away with the clearance of bone marrow. The other thing I was very happy to see was the safety of this therapy compared to other CAR-T cell therapy, [where] we are seeing severe CRS and ICANS including prolonged cytopenia. The overall incidence of CRS was quite manageable, and severity was so low that now we are treating most of our patients on this trial on a complete outpatient basis. ” 13 © © 2024 2024 P Po os se ei id da a T Th he er ra ap pe eu ut ti ics cs, , I In nc. c. Al All l Ri Righ ght ts s Re Res se er rv ve ed d. .


I was very impressed with the overall “ response rate. The overall response rate in the patients who were BCMA naive was 100%, and the overall response rate in patients who were BCMA exposed was 86%. KEY OL QUOTES FROM FIRESIDE CHAT And even in the seven patients who had exposure to BCMA and talquetamab or GPRC5D, the overall response rate was 86%. That's quite impressive in this, in fact, quite refractory patient population. And the duration of response was also quite impressive. So, between 5 and 10 months. ” 14 © © 2024 2024 P Po os se ei id da a T Th he er ra ap pe eu ut ti ics cs, , I In nc. c. Al All l Ri Righ ght ts s Re Res se er rv ve ed d. .


P-BCMA-ALLO1 is a first-in-kind allogeneic CAR-T for multiple myeloma MM is a common and incurable FDA Regenerative Medicine blood cancer, with ~12,500 Advanced Therapy (RMAT) and 1 P-BCMA-ALLO1 estimated U.S. deaths in 2024 Orphan Drug Designation (ODD) Anti-BCMA CAR ~179,000 people living with Healthy donor-derived, non- myeloma in the U.S., treated viral, T -rich CAR-T with Partial beta-2 SCM 1 microglobulin knock across multiple lines of therapy novel VH binder out T cell SCM Large market, ~$23B global, Developed in collaboration U.S. ~$14B, projected to grow with Roche; Phase 1b clinical 2 at 9-10% annually TCR knock out trial underway Manufactured by Poseida in Auto CAR-T deliver meaningful La Jolla, CA outcomes but only ~10% of patients 2 can benefit today 1. SEER, American Cancer Society. 2. EvaluatePharma – 2024 projections for Global / US sales. CAGR calculated based on 2024-2036 sales projections. Patients receiving treatment calculated based on sales projections and estimated average sale price for marketed autologous CAR T. ClearView Healthcare Partners Analysis. 15 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. MM = multiple myeloma


An allogeneic approach can greatly simplify and enable patient access to transformational CAR-T PATIENT RESPONSE 30 DAYS AFTER TREATMENT TREATMENT 1 DECISION INFUSION INITIATION WEEKS to MONTHS AUTOLOGOUS PATIENT JOURNEY SCHEDULE POTENTIAL BRIDGING PATIENT CELL SHIPMENT PATIENT FOR NEED FOR THERAPY PROCESSING APHERESIS RE-APHERESIS (4-8 HRS) MONTHS TIME TO CLINICAL BENEFIT ALLOGENEIC PATIENT JOURNEY * ~3.5 TREATMENT HEALTHY DONOR PATIENT DECISION PRODUCT SHIPPED RESPONSE WEEKS TIME TO CLINICAL * 16 DAYS TREATMENT Based on Poseida BENEFIT AFTER INITIATION Clinical Trial INFUSION Experience 1 DAY Source: Adapted from Elverum K, Whitman et al. Gene Therapy. April 2019. 1. Carvykti [package insert] - median time to first response 16 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. was 1 month. *Based on interim data from Phase 1 P-BCMA-ALLO1 clinical trial announced at IMS in September 2024, Arms A and B.


P-BCMA-ALLO1 Phase 1: Background and methods Phase 1, open-label, dose escalation study in patients with relapsed/refractory multiple myeloma • Must have had ≥ 3 prior lines of therapy including a PI, IMiD & • Primary Objectives: Safety and MTD/RDE CD38 mAb or be triple refractory • Secondary Objectives: Anti-myeloma effect; cell dose & • Prior BCMA targeting therapy allowed lymphodepletion regimen selection • ECOG 0 or 1 Dosing Information † Arm/LD dose (mg/m²)* P-BCMA-ALLO1 Dose (cells/kg) Total Patients 6 Arm S (Cy 300/ Flu 30) Range of 0.25-6 X 10 N=25 6 Arm A (Cy 500/ Flu 30) 2 x 10 N=19 6 Arm B (Cy 1000/ Flu 30) 2 x 10 N=10 6 Arm C (Cy 750/ Flu 30) 2 x 10 N=23 † Arm S includes 3 retreated subjects (received second lymphodepletion regimen followed by second P-BCMA-ALLO1 cell dose) and 1 subject treated with two P-BCMA-ALLO1 cell doses following one LD; Arm C includes 2 retreated subjects; BCMA, B cell maturation antigen; CAR-T, chimeric antigen receptor T-cell; CD38, cluster of differentiation 38; Cy, cyclophosphamide; ECOG-PS, Eastern Cooperative Oncology Group Performance Status; Flu, fludarabine; IMiD, immunomodulatory imide drug; L ​ D, lymphodepletion; mAb, monoclonal antibody; MTD, maximum tolerated dose; PI, protease inhibitor; RRMM, relapsed/refractory multiple myeloma. * Flu/Cy given × 3 days. All patients in arms A, B and C dosed at P-BCMA-ALLO1 cell dose with range of 1.822 to 5.589 × 106 cells/kg th Data cutoff for safety analysis was July 31st, 2024, and September 6 , 2024, for efficacy analysis. 17 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


P-BCMA-ALLO1 is highly clinically active in BCMA-naïve and BCMA-experienced patients PR VGPR CR sCR 100% 100% 91% 86% 86% 82% 80% 60% 40% 20% 00% Arm C Arm C Arm C Arm C Arm C (n = 23) BCMA-naïve ≥ 1 prior BCMA ≥ 1 prior BCMA and Prior Bispecific*** (n=9*) (n=14*) GPRC5D** (n=7*) (n=11*) Arm ORR= sCR, CR, VGPR or PR, including confirmed and unconfirmed responses. Evaluable patients: Obtained first response assessment by IMWG m-protein criteria or PD/death and completed 2 2 6 Week 4 visit. Arm: C = LD – cy 750 mg/m , flu 30mg/m .. All dosed Cohort 2 = Range 2.0 to < 6.0 × 10 cells/kg. Note: 2 Re-Treatment subjects included in arm C. *Includes 1 retreatment subject *** **talquetamab, a GPRC5D bispecific T cell engager Patients may have received another BCMA targeting agent in addition to bispecific PR, partial response; VGPR, very good partial response; CR, complete response; sCR, stringent complete response. 18 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Overall Response Rate, %


P-BCMA-ALLO1 Phase 1: A higher risk, difficult to treat and more refractory patient population* 5 6 2 3 4 KarMMa Cartitude-1 MajesTEC-1 MonumenTAL-1 MagnetisMM-3 P-BCMA-ALLO1 P-BCMA-ALLO1 Idecel Ciltacel Elranatamab 1 1 Talquetamab Teclistamab all patients arm C N=128 N=97 N=165 N=130 N=123 N=72 N=21 (subcut cohorts) 45 (35%) 35 (36%) 24 (15%) 37 (29%) 80 (65%) Age group > 65, # (%) 43 (60%) 10 (48%) (age≥ 75) (age >=70) NA 20 (21%) 31 (19%) 23 (18%) 26 (21%) Minority patient 24 (33%) 8 (38%) representation 57 (45%) 39 (40%) 55 (33%) -- 45 (37%) ECOG 0 12 (29%) 8 (38%) 45 (35%) 23 (24%) 38** (26%) 18 ***(16%) 31 (25%) High risk cytogenetics, 50 (69%) 13 (62%) # (%)* 19 (26%) 8 (38%) 50 (39%) 13 (13%) 8 (20%) -- 39 (32%) EMD, # (%) {incl. bone-based lesions} 120 (94%) 87 (90%) 135 (81%) 111 (85%) -- Previous ASCT 42 (58%) 14 (67%) 0 0 0 42 (34%) 0 1 prior anti-BCMA/GPRC5D 31 (43%) 13 (62%) (# of prior BCMA not specified) 0 0 0 -- 0 Multiple prior 15 (21%) 8 (38%) BCMA/GPRC5D 112 (88%) 73 (75%) NA NA NA Bridging Therapy, # (%) 0 (0%) 0 (0%) *Defined as the presence of Del 17p, t(14;16), t(4;14) for comparators; defined as t(4:14), t(14:16); p53 deletion; del17p; t(14:20); gain 1q for P-BCMA-ALLO1; No head-to-head trial has been conducted evaluating P-BCMA-ALLO1 against other products included herein. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, study design, and other factors; **Reported as 38/148 patients ***reported as 18/112 patients. 5 6 1 2 3 4 interim data as of Jul 31st, 2024. Munshi et al.; Berdeja et al.; Martin et al. (2023). Chari et al, 2022 Lesokhin, et al. 2023 19 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


P-BCMA-ALLO1 early safety and efficacy results appear encouraging in comparison with marketed autologous CAR-T therapies* Safety Efficacy 1 2 Late-line ABECMA CARVYKTI P-BCMA- Late-line MM ABECMA CARVYKTI P-BCMA-ALLO1 1 2 MM Patients ALLO1 (Arm C) Patients (ITT) (ITT) (ARM C) Safety Pop N=349 N=285 N=23*** Efficacy Pop N=135 N=113 N=23*** CRS, All Grade 89% 84% 39% 2 2 40% ICANS, All Grade 13% 13% ORR 53% 84% 91% (all CAR-T Neurotox) All infections 61% 57% 47% sCR + CR 21% 69% 22%** Parkinsonism Yes Yes No VGPR+ 39% 81% 48%** Bridging Tx Yes Yes No SPM signal Yes Yes No P-BCMA-ALLO1 had consistent and favorable safety profile in both BCMA-naïve & BCMA-experienced patients No DLTs, no grade ≥3 CRS or ICANS, no GvHD, no parkinsonism Quick cytopenia resolution and low serious infection rates ABECMA, CARVYKTI and TECVAYLI enrolled BCMA-naïve patients only *No head-to-head trial has been conducted evaluating P-BCMA-ALLO1 against other products included herein. Cross-trial data 1. . Abecma [package insert]. Summit, NJ: Celgene Corporation; 2024; 2. Carvykti [package interpretation should be considered with caution as it is limited by differences in study population, study design, and other insert]. Horsham, PA: Janssen Biotech; 2024 factors. **Data Maturing *** Includes unconfirmed responses and 2 retreated subjects. Full safety database includes N=72 and results are consistent with Arm C. 20 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. SPM, secondary primary malignancy; DLT, dose limiting toxicities; CRS, cytokine release syndrome; ICANS, immune effector cell associated neurotoxicity syndrome; GvHD, graft versus host disease; ORR, overall response rate


P-BCMA-ALLO1 early safety and efficacy results appear encouraging in comparison with marketed bispecific therapies* Safety Efficacy 1 2 3 Late-line TALVEY TECVAYLI ELFREXIO P-BCMA- Late-line TALVEY TECVAYLI ELREXFIO P-BCMA- 1 2 3 MM Patients ALLO1 MM (ITT) (ITT) (ITT) ALLO1 (Arm C) Patients (ARM C) Safety Pop N=339 N=165 N=183 N=23*** Efficacy 2 N=87 N=110 N=97 N=23*** 2 Pop CRS, All Grade 76% 72% 58% 39% 9% ICANS, All Grade 6% 3% 13% ORR 74% 62% 58% 91% (N=265) sCR + CR 33% 28% 26% 22%** All infections 53% 61% 42% 47% VGPR+ 58% 57% 52% 48%** SPM signal - - - No Bispecifics are dosed weekly and in cycles after cycles, tethering the patient to the medical center affecting the quality of life of the patient; meanwhile CAR-T has “one and done” dosing approach. 1. Talvey [package insert]. Horsham, PA: Janssen Biotech, 2023; 2.Tecvayli [package insert]. *No head-to-head trial has been conducted evaluating P-BCMA-ALLO1 against other products included herein. Horsham, PA: Janssen Biotech; 2022. 3. Elrexfio [package insert]. New York, NY Pfizer Inc: 2023. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, study design, and other factors. **Data Maturing *** Includes unconfirmed responses and 2 retreated subjects. 21 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Full safety database includes N=72 and results are consistent with Arm C.


NEW P-BCMA-ALLO1 effectively targets mutations that are known to arise in patients DATA with relapse after prior anti-BCMA therapies P-BCMA-ALLO1 kills tumor cells expressing wild type BCMA or clinically identified BCMA escape mutants BCMA P33Del BCMA P33S BCMA S30Del BCMA WT BCMA R27P 4 4 4 3 3 3 3 2 2 2 2 1 1 1 1 0 0 0 0 0 20 40 60 0 20 40 60 0 20 40 60 0 20 40 60 Time elapsed (Hrs) Time elapsed (Hrs) hour Time elapsed (Hrs) Poseida data on file 22 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. 2 Tumor cell Total Area (µm / image) normalized to time = 0 hr


Patients across Arms A, B, and C show response in disease markers, with encouraging early mTTR and mDOR a Percent Change by Subject, Color-Coded by Group Median Time to Median Duration of Response Response for Patients Groups Arm A Arm B Arm C with > 6 Months of (Pooled Arms A + B) Follow Up 0 (Pooled Arms A + B) -20 16 Days 232 Days -40 (95% CI 15 - 22) (95% CI 158 - 308) -60 Note: Arm C is the least mature cohort -80 (most recently enrolled). Current median follow up of Arm C is less than 3.5 months, therefore DOR could not be -100 estimated at this time Patients a The % change on Y axis is based on the myeloma parameter that was measurable at baseline and is used to determine response on each subject over time, such as SPEP, UPEP or FLC. MTTR: median time to response; mDOR: median duration of response; SPEP, serum protein electrophoresis; UPEP, urine protein electrophoresis; FLC, free light chain. 23 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Percent Change in M-protein or light chains


Summary: P-BCMA-ALLO1 demonstrates compelling early efficacy and safety results in heavily pretreated patients while delivering on the patient experience promise High efficacy (ORR) in BCMA-naive Compelling Emerging Safety Superior Patient Experience 1 2 and BCMA-experienced patients Results • ORR in Arm C is 91% • Differentiated safety vs. auto • 100% of enrolled patients treated CAR-T and bispecific/T-cell with in-spec product • 100% ORR in BCMA naïve engagers patients • Outpatient optionality for ease • No GvHD, DLTs, Parkinson's-like and reimbursement • Impressive efficacy seen in BCMA symptoms observed experienced patients, • No waiting…available on-demand including 86% ORR in pts with ≥ 1 • Low CRS, neurotoxicity all Gr ≤2 from inventory prior BCMA/ ≥ 1 prior BCMA + • Majority of AEs were Grade 1/2 – No invasive patient apheresis GPRC5D • Fully non-viral approach and – No anti-myeloma bridging • P-BCMA-ALLO1 is effective available safety switch vs. therapy following prior bispecific therapy autologous/virus SPM concerns with an 82% ORR • ~3.5 weeks from patient enrollment to clinical response 2 ¹ Interim data as of September 6, 2024. Interim data as of July 31, 2024 24 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Phase 1b study schema, dose expansion is actively enrolling two dosing cohorts Phase 1/1b, open-label, dose expansion study in patients with relapsed/refractory multiple myeloma Key Inclusion: • Primary Endpoints: ORR based on IMWG criteria • Secondary Endpoints: Safety, tolerability and efficacy of • Must have had ≥ 3 prior lines of therapy including a PI, P-BCMA-ALLO1 (ORR, CR/sCR, TTR, DOR, PFS, OS) IMiD & CD38 mAb or be triple refractory • Documented measurable disease • Exploratory Endpoints: MRD, cellular kinetics, BCMA expression in the bone marrow, soluble BCMA in the • ECOG 0 or 1 blood • n=40 P-BCMA-ALLO1 Dosing level 1 Cy750/Flu30 Ongoing response & safety assessments Dosing level 2 P-BCMA-ALLO1 IMWG, International Myeloma Working Group; MRD, minimal residual disease; DOR, duration of response; PFS, progression-free 25 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. survival; OS, overall survival; TTR, time to response


P-CD19CD20-ALLO1 – Poseida’s first dual CAR-T is being developed in partnership with Roche Differentiated, carrying 2 full length CARs 1 and other Poseida platform elements • Relapse due to target escape remains a common problem Preclinical data planned CD19 in B-cell malignancies CD20 MHC I for ASH 2024; Clinical knock-out • Early autologous CD19/CD20 data planned for 2025* CAR-T data suggests dual TCR targeting can be more knock-out effective Status Clinical Trial • Multiple learnings from other Poseida programs have • Phase 1 study enrolling selected B-cell malignancies, prior been incorporated Auto CAR-T and TCE is allowed (NCT04960579) • Dose escalation is ongoing • 3x3 design, with flexibility for expansion, exploring multiple LD regimens *Subject to coordination with Roche 26 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. 1. Safety switch, selectable marker, TCR KO, β2M KO


NEW P-CD19CD20-ALLO1 is a potent CAR-T product against CD19- and CD20-dual DATA positive B-Cell malignancies • High in vitro potency against CD19- and CD20-positive Raji model • High in vivo antitumor efficacy across CAR-T lots produced from multiple healthy donors and dose levels In vitro potency In vivo antitumor efficacy 11 100 10 10 10 80 PBS (no CAR-T) 9 10 60 Naïve Donor 1 6 6 6 8 10x10 10x10 10x10 10 Donor 2 40 6 6 6 5x10 5x10 5x10 Donor 3 7 10 6 6 6 20 2.5x10 2.5x10 2.5x10 6 6 6 6 10 1x10 1x10 1x10 0 5 10 0.01 0.1 1 10 100 0 10 20 30 40 E:T Ratio Days Post CAR-T Infusion Figure 2. P-CD19CD20-ALLO1 CAR-T cells produced from three healthy donors exhibit robust antitumor efficacy against CD19- and CD20-dual positive Raji Burkitt’s lymphoma cell line in vitro and in vivo. Left Panel. Luciferase-expressing WT Raji cells (CD19+CD20+) were co-cultured for 48 hours with P-CD19CD20-ALLO1 CAR-T cells at the indicated Effector:Target (E:T) ratios and viable cells were quantified using a luminescence-based assay. Cytotoxicity was calculated by normalization to Raji cells alone samples. Right Panel. NSG mice were intravenously implanted with WT Raji (CD19+CD20+) cells and received 4 days later the indicated doses of P- CD19CD20-ALLO1 CAR-T cells. Tumor burden was monitored by bioluminescence imaging. Data is presented as mean ± SEM (n=5 mice/group). 27 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Cytotoxicity (%) Total Flux (p/s) Donor 1 Donor 2 Donor 3


NEW P-CD19CD20-ALLO1 may prevent relapse due to antigen escape by DATA targeting single-positive tumor cells • P-CD19CD20-ALLO1 shows dose-dependent and high tumor control in two in vivo models of antigen escape Raji CD19 KO (CD20+) Raji CD20 KO (CD19+) 11 11 10 10 PBS (no CAR-T) PBS (no CAR-T) 10 10 10 10 Naïve Naïve 9 9 6 10 10 6 10x10 10x10 6 6 8 8 5x10 10 10 5x10 6 6 2.5x10 2.5x10 7 7 10 10 6 6 1x10 1x10 6 6 10 10 5 5 10 10 0 10 20 30 40 0 10 20 30 40 Days Post CAR-T Infusion Days Post CAR-T Infusion Figure 3. Dual-targeting P-CD19CD20-ALLO1 CAR-T cells can prevent relapse due to antigen loss. P-CD19CD20-ALLO1 show strong in vivo antitumor efficacy against Raji cells genetically engineered to express only CD20 (CD19 KO – left panel) or CD19 (CD20 KO – right panel) in a dose-dependent manner. NSG mice were intravenously implanted with CD19 or CD20-single positive Raji cells and 4 days later received the indicated doses of P-CD19CD20-ALLO1 CAR-T cells. Tumor burden was monitored by bioluminescence imaging. Data is presented as mean ± SEM (n=5 mice/group). 28 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Total Flux (p/s) Donor 1 Total Flux (p/s) Donor 1


NEW P-CD19CD20-ALLO1: Robust killing of B cells from primary human DATA autoimmune PBMCs • P-CD19CD20-ALLO1 assayed for cytotoxicity against B cells in primary human PBMCs from autoimmune patients (RA, SLE, MS) ⎯ Average of 3 lots of P-CD19CD20-ALLO1 (3 unique donors) • Robust depletion of B cells in most samples at 5:1 E:T ⎯ No cytotoxicity observed against NK cells or macrophages above no CAR-T controls ⎯ CD20+ T cell depletion was expected and observed • ~5-8% of T cells in MS are CD20+; <2% in healthy donors • Data are similar to P-BCMA-ALLO1 cytotoxicity against cancerous B cell lines E:T, Effector:Target ratio 29 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


P-CD70-ALLO1: Introducing an IND-enabling stage asset with multi-indication potential, including in heme malignancies and solid tumors TCR KO Partial B2M KO CD70 knockdown Key features Novel allogeneic, T -rich CD70-targeting CAR-T engineered for potency, SCM safety, and manufacturability • Unique shRNA knockdown of CD70 from a multi-cistronic transgene to avoid fratricide and increase potency, with no genotoxicity risk • Potent cytotoxicity against CD70+ AML cell lines in vitro and in vivo, without impacting normal hematopoietic stem and progenitor cells • Ablates CD70+ activated alloreactive lymphocytes, which may prolong persistence by inhibition of immune rejection (T cell shield) Proof-of-concept exists for use of CD70 approaches in solid (RCC) and liquid tumor (AML), including from early CAR-T studies and monoclonal antibodies Safety switch CD70 CAR • Roche has an exercisable option on this program P-CD70-ALLO1 has great potential in high unmet medical need diseases 30 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


CD70 is an attractive antigen target for CAR-T, given expression levels as well as early clinical evidence in solid and liquid tumors Solid tumors CD70 expression seen across tumor types Liquid tumors AML Lymphomas Flieswasser T et al, 2019 Perna F et al. 2017 Early clinical validation of CD70 exists across modalities (CAR-T, ADCs) 1,2 and therapeutic areas (AML, RCC) , with a solid emerging safety 3 record attributed to no expression on normal hemopoietic stem cells Flieswasser T, et al, 2019 1 2 3 Pabst et al. 2023. Pal SK et al. 2024. Perna et al, 2017; Riether et al, 2017; Sauer et al 2021. 31 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


NEW Poseida approach using robust shRNA-mediated depletion (knockdown) of DATA CD70 yields CAR-T with optimal in vivo potency Superior to CD70 knockout through gene editing Highly efficient knockdown of CD70 in Robust in vivo activity against AML models CAR-T cells using shRNA 98 shRNA KO 193 WT 1,923 FMO 101 CD70 AML, acute myeloid leukemia; FMO, fluorescence-minus-one control; KO, knockout; PBS, phosphate buffered 32 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. saline; shRNA, short hairpin ribonucleic acid; WT, wildtype


NEW DATA P-CD70-ALLO1 exhibits robust anti-AML effect in vivo with no HSC toxicity P-CD70-ALLO1 has robust in vivo potency against Healthy donor HSC are killed by c-Kit & CD123 CAR- CD70+ AML Nomo-1 xenograft T, but not by P-CD70-ALLO1 or control PSMA CAR-T Nomo-1 150 12 10 PBS Control Threshold 11 6 10 2.5 × 10 P-CD70-ALLO1 100 10 10 9 10 50 8 10 7 10 0 6 10 0 10 20 30 40 Days Post CAR-T Injection Note: P-CD70-ALLO1 cells were produced from 3 individual healthy donors, and co-cultured with healthy donor HSC 33 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. P-CD70-ALLO1 PSMA CAR-T c-Kit CAR-T CD123 CAR-T Photons/sec %colonies remaining (norm. to CD34+ alone)


From hematology to autoimmune disease: Poseida’s BCMA-CD19 dual CAR-T Kurinji Pandiyan, PhD Vice President, Portfolio & Strategy


CAR-T and related immunotherapies show great promise and present new questions in autoimmune disease 2021 2022 – 2024 Today’s questions Best therapeutic Optimal • Seminal results from Georg Schett • Rapid pivot of oncology / cell modality? safety? group sparked explosive interest therapy companies, especially allogeneic players • Many trials underway in multiple diseases Target selection? Mixed Results: Disease • Encouraging early efficacy, selection? including allogeneic • Questions emerging on safety, • Unmet need and market durability of remissions potential appear vast Optimal durability Conditioning approach? of remission? 35 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Poseida’s clinically validated T -based platform is well-suited to autoimmune SCM disease applications DE SI RED P R OF I L E OF I M M UN O TH ERA P Y P OSEI D A F OR A UT OI M M UN E DI SE A SE P L ATF ORM F E ATURE S ü Clinical validation of CAR-T through oncology work SCM • Deep depletion of B cells, then rapid recovery ü Pipeline programs include targets of interest (BCMA, CD19, CD20, CD70) Efficacy • Ability to target cell populations of interest ü Transposon technology enables multi-target dual CARs, CAR-TCRs ü Distinctively low rates & mild in oncology, despite higher cell burden • Near term tolerability (CRS, neurotox, infections) Safetyü Fully non-viral technology, rapid-acting embedded safety switch • Long term safety (secondary malignancies) ü High fidelity gene editor ü Some Poseida oncology patients receiving all treatment outpatient Patient reach & • Immediate and reliable treatment ü Multiple lymphodepletion strategies experience • Outpatient and community care settings ü Off-the-shelf, to simplify logistics and treat patients with no waiting • Ability to meet patient demand in higher – Manufacturing ü Proven ability to manufacture at scale from healthy donors prevalent diseases scalability for ü Targeting biologics-like COGM • COGS able to support AID volume proposition volume & COGS AID, autoimmune disease; CRS, cytokine release syndrome; COGS, cost of goods sold; COGM, cost of goods manufactured 36 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


P-BCMACD19-ALLO1 (IND-enabling stage): Poseida’s wholly owned investigational therapy for autoimmune disease and hematological malignancies P-BCMACD19-ALLO1 • Potent cytotoxicity against BCMA and CD19, a key feature for both autoimmune disease and in oncology given cells that need to be targeted • Key construct attributes: – Dual CAR configuration, with tandem BCMA CAR, for optimal potency – Intracellular domain (ICD) combination gives superior potency – Incorporation of Poseida allo platform & process improvements Safety switch • Preclinical proof-of-concept established for use of BCMA-CD19 in BCMA autoimmune and oncology models Tandem CAR • Clinical validation of dual BCMA-CD19 targeting with autologous CAR-T CD19 CAR 37 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


AUTOIMMUNE DISEASE NEW DATA P-BCMACD19-ALLO1: Robust killing of B cells across multiple autoimmune diseases In vitro proof-of-concept in autoimmune disease Rheumatoid Arthritis PBMCs Systemic Lupus Erythematosus PBMCs Multiple Sclerosis PBMCs 200 200 200 E:T 1:1 E:T 5:1 E:T 1:1 E:T 5:1 E:T 1:1 E:T 5:1 Mock T Cell Control 150 150 150 P-BCMACD19-ALLO1 100 100 100 (2 unique donors) 80 80 80 60 60 60 40 40 40 20 20 20 0 0 0 Robust in vitro elimination of primary autoimmune patient derived B cells across different effector to target ratios 38 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. PBMC, peripheral blood mononuclear cells MS Donor 1 MS Donor 2 MS Donor 1 MS Donor 2 RA Donor 1 RA Donor 2 RA Donor 3 RA Donor 1 RA Donor 2 RA Donor 3 SLE Donor 1 SLE Donor 2 SLE Donor 3 SLE Donor 1 SLE Donor 2 SLE Donor 3 % Surviving B cells % Surviving B cells % Surviving B cells


AUTOIMMUNE DISEASE NEW DATA P-BCMACD19-ALLO1 depletes primary human B cells in humanized mouse model In vivo proof-of-concept of robust B cell depletion PBS control Dose level 3 Dose level 2 Dose level 1 800 800 800 800 600 600 600 61% depleted 600 83% depleted 77% depleted 400 400 400 400 200 200 200 200 0 0 0 0 0 7 14 21 28 0 7 14 21 28 0 7 14 21 28 0 7 14 21 28 Days post CAR-T injection Days post CAR-T injection Days post CAR-T injection Days post CAR-T injection Days post CAR-T injection (N=3 mice) Dose-dependent depletion of primary B cells in a humanized NOG-EXL mouse model generated with human CD34+ cells 39 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. NOG-EXL, highly immunocompromised mouse model B-cell counts/ μL of blood B-cell counts per μL of blood B-cell counts per μL of blood B-cell counts per μL of blood B-cell counts per μL of blood


Immense potential of P-BCMACD19-ALLO1 to address growing needs across autoimmune diseases Illustrative examples, not exhaustive Deeper, more durable response, potential in diseases with emerging Plasma cell and B cell targeting have strong mechanistic relevance CAR-T efficacy Myasthenia Gravis 70K Lupus (SLE & LN) 370K 140K IgA Nephropathy Immune Mediated 46K- 100K ANCA Vasculitis Myopathies 70K Systemic Sclerosis 100K Large product scale and off-the-shelf availability is Significant unmet need across autoimmune diseases, important to meet patient needs yet to be explored for CAR-T treatment Rheumatoid Arthritis 1.3M Membranous 70K Nephropathy Autoimmune 22K Encephalitis Sjögren’s syndrome 340K IgG4 Related Disease 18K 950K – Multiple Sclerosis 1M Estimated U.S. prevalence, not to scale 40 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Sources: Global Data, Evaluate


ONC OL OG Y NEW DATA P-BCMACD19-ALLO1 effectively eliminates BCMA+ multiple myeloma bulk tumor cells and CD19+ bone marrow progenitor cells Progenitor killing with CD19+ targeting Potent killing of MM cell lines with BCMA+ targeting - + BCMA CD19 progenitors (primary patient samples, n=4) MM patients (N=4) P-BCMACD19-ALLO1 Mock T cell control Anti-BCMA CAR-T Anti-CD19 CAR-T 100 75 + - Control cell lines BCMA CD19 MM cells 100 50 + + - - BCMA CD19 BCMA CD19 100 100 75 25 75 75 50 0 50 50 25 25 25 0 0 0 Effector : Target Ratio Effector : Target Ratio 41 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Anti-BCMA CAR-T Anti-CD19 CAR-T P-BCMACD19-ALLO1 % Killing 10:1 5:1 2.5:1 1.25:1 0.625:1 % Killing 10:1 5:1 2.5:1 1.25:1 0.625:1 10:1 5:1 2.5:1 1.25:1 0.625:1 % Killing of CD81+CD19+ cells (Relative to MOCK control)


ONC OL OG Y NEW DATA Tandem BCMA binder has equal activity against wild-type (WT) BCMA & identified clinical escape mutants, including teclistamab-associated mutation R27P BCMA tandem binder effectively binds BCMA mutant Potent cytotoxicity against WT & BCMA mutant cells BCM BCM A R2 A R2 7P 7 (m P utant) BCMA WT BCMA R27P (mutant) 100 BCMA mAB control BCMA tandem binder 4 4 80 BCMA mono-binder 1 BCMA mono-binder 2 3 60 3 Target only 40 2 2 20 1 1 BCMA mono-binder 2 0 BCMA tandem binder 0 0.01 0.1 1 10 0 0 20 40 60 0 20 40 60 Protein Concentration (μg/mL) Time elapsed (Hrs) Time elapsed (Hrs) In vitro binding assay of BCMA R27P protein In vitro cytotoxicity against K562 expressing BCMA WT or R27P mutant expressed by K562 cells via mRNA Note: Binding to other BCMA isoforms (WT, P33Del, P33S and S30Del) also confirmed (data not shown) 42 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. % Protein bound to cells by FACS Tumor Growth (relative to input) 2 Total Area (µm / image) normalized to time = 0 hr


Waves of innovation in solid tumor cell therapy Devon J. Shedlock, PhD CSO, Cell Therapy


Solid tumors pose unique challenges for development, requiring bold innovations to overcome and address significant unmet need No CAR-Ts approved for solid tumors* Key roadblocks 90% 1.8M of cancers are Estimated 1 1 solid tumors incidence (U.S.) CAR-T Cell Tracking & Antigen Heterogeneity Infiltration 550K $190B Hostile Tumor 2 Patients dying Market size On Target Off Tumor Tox Microenvironment 1 annually (U.S.) B O L D IN N O V AT IO N S A N IMP E R AT IV E * Does not include approvals for engineered T cell receptor (TCR) and tumor-infiltrating lymphocyte (TIL) therapy 1. SEER, American Cancer Society (2024) – solid tumor estimates 44 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. 2. Global Market Size in 2023. Source: Global Oncology Trends, 2024 (IQVIA)


Poseida’s flexible platform sets up waves of innovation in allogeneic cell therapy for solid tumors, including entirely new platforms First Generation Second Generation Third Generation P-MUC1C-ALLO1 P-PSMA-ALLO1 CAR-TCR Platform Prostate cancer Pan-solid tumor Platforms may be advantageous across cCAR Allo-T (Astellas) oncology and other disease areas Pan-solid tumor MUC1C + epithelial tumors Time • Leveraging clinical experience from • Initial foray into solid tumors with • New technology leveraging clinical P-PSMA-101 Allo-T platform learnings and our Allo platform / SCM process advances • New technologies and process • Significant learnings on science, LD strategies lymphodepletion needs • CAR-TCR targets both extra- and – Modifications for viability, potency intracellular tumor-associated • Initial exploration of LD + low- persistence antigens dose MTX • Robust Allo-T platform + flexible SCM – CAR-TCR / TCE synergy targeting with Astellas cCAR MUC1C, C-terminal domain of Mucin 1; T , stem memory T cell; LD, lymphodepletion; MTX, methotrexate; PSMA, prostate- SCM 45 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. specific membrane antigen; Allo, allogeneic; cCAR, convertible CAR; TCR, T cell receptor; TCE, T cell engager Projected Value


F I RST G ENER AT I ON P-MUC1C-ALLO1 is Poseida’s lead solid tumor allogeneic CAR-T program P-MUC1C-ALLO1 Motivation Exploit (MTX) resistance of Poseida's CAR-T for unique, additive LD strategy • High unmet medical need in many epithelial cell-derived tumors 150 P-MUC1C-ALLO1 • Poseida’s earlier autologous PSMA Stimulated program showed clinical potential of Pan T Unstimulated 100 T -rich CAR-T in a solid tumor Pan T Stimulated SCM 50 Clinical Trial 0 0 250 750 • Phase 1 basket study enrolling treatment MTX Concentration (nM) resistant breast, ovarian, colorectal and Unique approach to • At low MTX doses, equivalent to those used for other tumors (NCT05239143) targeting MUC1C protein at autoimmune disease therapy, activated T cells tumor specific moiety • 3x3 dose escalation; Poseida-produced are killed, while P-MUC1C-ALLO1 cells are not GMP product Also carries Poseida’s • LD/MTX approach may enhance CAR-T 1 platform elements • Ongoing exploration of dosing regimen expansion/persistence and is in study design and lymphodepletion Data update planned for ESMO-IO 2024 1. Safety switch, selectable marker, TCR KO, β2M KO PSMA, prostate-specific membrane antigen; T , stem memory T cell; GMP, good manufacturing practice; TCR, T cell receptor; B2M, beta-2 microglobulin; 46 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. SCM MUC1C, C-terminal domain of Mucin 1; LD, lymphodepletion; SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; nM, nanomolar; MTX, methotrexate % Survival


F I RST G ENER AT I ON NEW DATA Substantial tumor size decrease and prolonged stable disease (~1 year) in patient with heavily pretreated appendiceal carcinoma Baseline Day 344 st 1 P-MUC1C-ALLO1 Dose Screening nd 2 Dose Baseline -39 -6 0 STUDY DAY 85 st nd LD – 1 Dose LD – 2 Dose 2 2 Cy 500 mg/m Cy 500 mg/m 2 2 Flu 30 mg/m × 3d Flu 30 mg/m × 3d Enlarged paraesophageal Paraesophageal lymph node lymph node: 42 mm decreased in size to 28 mm (42% decrease) MUC1C, C-terminal domain of Mucin 1; LD, lymphodepletion; Cy, cyclophosphamide; Flu, Fludarabine; mm, millimeter 47 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


SECOND GENERATION NEW DATA P-PSMA-ALLO1 builds upon Poseida’s earlier PSMA autologous CAR-T program to tackle prostate cancer Multiple cell expansion and potency enhancements to deliver best product profile • Dual CAR format has shown KO for safety and improved efficacy compared to New process immune stealth the autologous program science TCR KO Centyrin binder in xenograft tumor models Engineered Partial B2M KO • P-PSMA-ALLO1 includes latest transposon and process development and ICD1 RNAs for cell yield, allogeneic CAR-T platform CAR expression, CAR1 improvements for improved ICD2 potency cell health, viability, potency, CAR2 and persistence Armoring to drive expansion Dual CARs, different and persistence binders and ICDs PSMA, prostate-specific membrane antigen; KO, knock out; TCR, T cell receptor; B2M, beta-2 microglobulin; ICD, intracellular domain 48 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


** SECOND GENERATION NEW DATA Fully dual CAR P-PSMA-ALLO1 outperformed single and tandem binder CAR-Ts In vivo screen of PSMA binder candidates Reactivity of Lead Dual CAR with PSMA isoforms PBS Control 45 CD8+ VHCAR1 40 1,500 CD4+ VHCAR2 35 Tandem VHCAR1-VHCAR2 30 1,250 Tandem VHCAR2-VHCAR1 25 Dual VHCAR1-VHCAR2 PSMA Isoforms 20 1,000 Dual VHCAR2-VHCAR1 (membrane-bound) 15 10 750 5 0 500 ns 250 0 0 7 14 21 28 35 42 49 RNA-engineered K562 cells Days Post-CAR T Infusion • Dual biparatopic PSMA CAR-T outperforms tandem and single • CAR-T with selected binders do not bind alternative PSMA VH CAR-T in vivo isoforms (expressed extratumorally) • Optimal combination of ICDs (E.g. CAR1-ICD1 + CAR2-ICD2) will be determined for PSMA dual CAR PSMA, prostate-specific membrane antigen; VH, heavy chain variable; PBS, phosphate buffered saline; ICD, intracellular domain 49 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. CAR T Only Control LNCaP PC.3 PSMA (PSMA-1) PSM-D (PSMA-7) PSME (PSMA-9) PSMAΔ6 PSMAΔ18 (PSMA-8) Control (No RNA) 3 Tumor Volume [mm ] Cytotoxicity (%CD107a+)


SECOND GENERATION Concept of Xyphos/Poseida Research collaboration for convertible Allo CAR-T SCM Allogeneic T SCM TM endoTCR KO Combine the Allo-T and ACCEL platform to target solid tumors MHCI KO Xyphos’ Poseida’s TM ACCEL Platform Allo-T cell platform TM CAR w/ MicAbody library αβTCR T Cell Engager γδTCR Therapy Combination Multi-targeting TM ACCEL platform, consisting of a modified TM mAb with engineered ligand (MicAbody ) Key features of the Allo-T platform, TM convertibleCAR expressing Allo-T cells TM and iNKG2D-based convertibleCAR with the range of possible modifications shown TM ü Combination of ACCEL and T aims to create a long lasting, highly active, but exquisitely controlled cancer killing CAR-T SCM ü The collaboration will provide us with the opportunity to utilize clinical stage allogenic T-cells to maximize the value of the TM ACCEL platform TM ü Xyphos’ MicAbody Library will be used in conjunction with Poseida’s ALLO-T platform ü Single T-cell design (iNKG2D T) with efficient manufacturing process T , stem memory T cell; endoTCR, endogenous T cell receptor; KO, knock out; MHCI, major histocompatibility complex class I; SCM 50 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Allo, allogneic; cCAR, convertible CAR; mAb, monoclonal antibody; iNKG2D, inert natural killer group 2 member D receptor


SECOND GENERATION NEW DATA TM Allogeneic universal cCAR-T and solid tumor-targeting MicAbody demonstrate compatibility of Poseida, Xyphos platforms TM Allogeneic iNKG2D CAR-T + Target 1 MicAbody in vitro cell killing assay (5:1 E:T ratio) • Allogeneic universal iNKG2D 120 cCAR-T in the presence of SCM MicAb conc. solid tumor antigen-targeting 100 10pM TM MicAbody demonstrates 100pM Target 1 MicAb A 80 1,000pM potent, specific in vitro 10pM 60 cytotoxicity 100pM Target 1 MicAb B 1,000pM 40 • Demonstrates potential to 1,000pM Negative Control MicAb develop a highly flexible family of 20 No MicAb Control drug products consisting of a 0 single off-the shelf Allo CAR- v1 v2 MOCK T cells TSCM matrixed with multiple iNKG2D CAR T TM MicAbodies T , stem memory T cell; cCAR, convertible CAR; iNKG2D, inert natural killer group 2 member D receptor; SCM 51 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. AUC, area under the curve; pM, picomolar; POC, proof-of-concept Tumor Cell Growth (AUC)


T H IR D G ENER AT ION Poseida is systematically exploring next-generation improvements for solid tumors to be used in ‘third-wave’ innovation Potency and persistence Armoring • Cell health, cell activation, • Armoring can block TME and pathway utilization for suppressive signals or co-opt maintenance of stemness for activation and expansion and optimal potency Immune escape Multi-Antigen targeting • T cell and NK cell shields can • Transposon transgene can increase drug exposure via express multiple CARs, γδ/αβ decreasing rejection by host TCR, enables use of TCE for immune cells targeting up to 4 unique antigens with a single CAR-T TME, tumor microenvironment; NK, natural killer; KO, knock out; KI, knock in; ICD, intracellular domain; miR, microRNA; MTX, methotrexate; 52 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Ag, antigen; abTCR, alpha-beta T cell receptor; gdTCR, gamma-delta T cell receptor; shRNA, short hairpin RNA; TCE, T cell engager


T H IR D G ENER AT ION A new platform for tough tumors: Poseida’s combination CAR-TCR technology is designed to address the challenges of adoptive cell therapy for solid tumors • Inclusion of one or more CARs and TCRs simultaneously (CAR-TCR Allogeneic T SCM technology) is enabled by large transposon cargo capacity endoTCR KO • Can combine classic CAR + γδTCR or αβTCR in single products • CAR-TCR addresses the heterogeneity of solid tumor antigen expression: MHCI KO – Recognize both cell-membrane (CAR) and cytoplasmic (TCR) antigens rd – Capable of engaging TCE therapeutic against a 3 target CAR – Potential to be used with TCR-T-priming reagent or vaccine • CAR-TCR potency and persistence: αβTCR – TCR provides additional survival signal for cell persistence T Cell Engager – TCR maintains high memory, low exhaustion phenotype for γδTCR longer duration Therapy Combination Multi-targeting – γδTCR may have advantages for trafficking, without need for HLA matching or GVHD risk T , stem memory T cell; endoTCR, endogenous T cell receptor; KO, knock out; MHCI, major histocompatibility complex class I; SCM 53 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. TCE, T cell engager; GVHD, graft-versus-host disease; TCE, T cell engager; HLA, human leukocyte antigen


T H IR D G ENER AT ION CAR-TCR T cells exhibit strong functional capabilities against both cell surface CAR target and intracellular TCR target Allo CAR + abTCR or CAR + gdTCRTs kill single and double-Ag positive tumor cells When exposed to double Ag+ cells, a higher % of Allo CAR + MUC1C CAR + NY-ESO-I αβTCR αβTCR vs CAR-T express ≥ 2 Target cells: No AntigenαβTCR-Antigen+ CAR-Antigen+ Dual-Antigen+ immune mediator cytokines [Peptide + MHCI] 6 2×10 Tumor Only 6 CAR-T 45 1.5×10 αβTCR+CAR-T 6 1×10 40 αβTCR-T 5 5×10 35 0 0 8 16 24 32 40 48 56 64 72 0 8 16 24 32 40 48 56 64 72 0 8 16 24 32 40 48 56 64 72 0 8 16 24 32 40 48 56 64 72 30 Time (hrs) 25 MUC1C CAR + pAg γδTCR 20 Target cells: No AntigenγδTCR-Antigen+ CAR-Antigen+ 15 [pAG + BTN2A/3A] 10 6 2×10 Tumor Only 6 5 1.5×10 CAR-T 6γδTCR+CAR-T 1×10 0 5 5×10 0 0 8 16 24 32 40 48 56 64 72 0 8 16 24 32 40 48 56 64 72 0 8 16 24 32 40 48 56 64 72 Time (hrs) TCR, T cell receptor; Allo, allogeneic; hrs, hours; Ag, antigen; MUC1C, C-terminal domain of Mucin 1; NY-ESO-1, New York esophageal 54 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. squamous cell carcinoma 1; MHCI, major histocompatibility complex class 1; pAg, phosphoantigen; BTN, Butyrophilin CAR-T CAR-TCR-T Total Green Area Total Green Area 2 2 (μm /image) (μm /image) % polyfunctional cells


Originally presented at SOHO/LLM T H IR D G ENER AT ION Inspirational case study: T cell engager reactivation and redirection of CAR-Ts This case study demonstrates the remarkable potential of T TCE talquetamab caused dramatic benign P-BCMA-101 “ reactivation years after CAR-T administration stem cell memory-based therapies, providing a strong anti- myeloma response with a long-term remission and, notably, CAR-T cell persistence. Most notably, we believe this is the first time that a T-cell Massive increase in P- BCMA-ALLO1 transgene engager has been seen to reactivate a CAR-T therapy, and the levels post talquetamab (peak 678,120 copies/µg evidence suggests that this reactivation drove a second wave of DNA) of CAR-T cell proliferation that led to another complete response three years after the initial successful CAR-T treatment. This patient is now off all anti-myeloma treatments and living in remission for more than nine months following 1 week of TCE therapy, a truly amazing outcome. • Pt received autologous P-BCMA-101, and achieved a sCR; in remission ~31 mo • >3 years after P-BCMA-101, pt received 1 wk of GPRC5D TCE - talquetamab Thomas G. Martin, M.D. • Dramatic benign polyclonal re-expansion of P-BCMA-101 Clinical Professor of Medicine, • sCR > 10 mo from last dose of TCE Adult Leukemia and Bone Marrow Transplantation Program and • Observation is possibly a unique feature of T -rich CAR-T products, such as SCM Director of Hematology, Blood and P-BCMA-101, that demonstrate tropism for the bone marrow and are more Marrow Transplantation and likely to result in durable engraftment Cellular Therapy at UCSF TCE, T cell engager; ALC, absolute lymphocyte count; qPCR, quantitative PCR; sCR, stringent complete response; pt, patient; GPRC5D, 55 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. G protein-coupled receptor, class C, group 5, member D; T , stem memory T cells; UCSF, University of California San Francisco SCM “


T H IR D G ENER AT ION Designing the CAR-TCR+TCE approach to work in allogeneic cell therapy: T cell engager reactivation and redirection of TCR+ CAR-Ts CAR+TCR-T synergized with TCE to control tumors expressing three unique antigens Patent filed 3 3×10 3 2.5×10 TCE No Treatment 3 CD70 2×10 αβTCR+CAR Alone 3 αβTCR+CAR + TCE 1.5×10 3 1.0×10 second tumor challenge 2 5.0×10 TCE injection • MUC1C-CAR + NY-ESO-1-TCR T cells: + + - ⎯ controlled primary tumor (MUC1C /NY-ESO-1 /CD70 ) 0 14 21 28 35 42 49 56 63 70 77 ⎯ later, were re-activated and re-directed by administration of a Study Day CD70 T cell engager (TCE) to control challenge by a secondary - - + tumor (MUC1C /NY-ESO-1 /CD70 ) TCR, T cell receptor; MUC1C, C-terminal domain of Mucin 1; b2,Mbeta-2 microglobulin; KO, knock out; 56 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. TCE, T cell engager; NY-ESO-1, New York esophageal squamous cell carcinoma 1 3 Tumor Volume [mm ]


The power of partnerships fireside chat Karen Basbaum Peter Sandor, MD SVP, Business Development EVP, Head of Corporate Strategy at Poseida Therapeutics at Astellas Pharma


In-house GMP manufacturing capabilities Loren Wagner Chief Operations Officer


Poseida manufactures GMP allogeneic CAR-T in house for higher yields and lower COGS Facility supports current needs for three allogeneic programs while simultaneously advancing our platform POSEIDA'S ALLOGENEIC VS. AUTOLOGOUS PLANT 1​ • ~1/10 facility size for comparable output 2​ • Far lower labor and operating costs • On demand product delivery to site of care​ • Reach 100% of patients via stored inventory​ • Targeting biologics-like COGS Efficient | Accessible | Flexible | Cost Effective | Off-the-shelf 1. Assuming autologous facility size is 150,000 sq. ft. 59 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. 2. Assumes an autologous facility workforce requires at least 900-1200 people Data on file


Poseida’s consistent platform reflects a holistic systems engineering approach to CAR-T set to deliver product after product Robust healthy donor screening system Non-viral gene insertion and gene editing “On-demand” delivery of therapy approaches the same across all programs, from inventory through supply chain and customized for T cells SCM Allogeneic CAR-T Enterprise Selectable marker supports purification so Poseida’s platforms Proprietary Booster Molecule enable the “capacity to that nearly all cells are CAR-carrying, with improves manufacturing yield cure” in a new class of the potential for optimal therapeutic index CAR-T therapies Unit operations optimization across process Safety “switch” to selectively eliminate development and quality, applied to all programs CAR-T cells in the patient, if necessary Poseida has taken a deliberate platform approach to develop a pipeline of allogeneic CAR-T programs that use the same proprietary technologies, the same manufacturing platform and reflect similar production methods 60 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


NEW Apheresis purity is variable among donors but consistent between DATA collections Donor 1 Donor 2 Donor 3 Donor 1 Donor 2 Donor 3 100 100 100 Collection 1 Collection 1 Collec Collection 2 Collection 2 Collec Collection 3 Collection 3 Collec 50 50 50 0 0 0 Note: All cell types are % of CD45+ cells in apheresis • All collections from a particular donor have similar cellular distributions in the apheresis • Cell distribution in the apheresis is donor-dependent 61 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Monocytes B Cells NK Cells NKT Cells T cells Impurities Monocytes B Cells NK Cells NKT Cells T cells Impurities Monocytes B Cells NK Cells NKT Cells T cells Impurities Percent of CD45+ cells (%) Percent of CD45+ cells (%) Percent of CD45+ cells (%)


NEW DATA Fold expansion during allogeneic CAR-T manufacturing is donor-dependent 20 15 There is significant donor variability in fold expansion 10 during CAR-T cell manufacturing 5 0 Lots/Donors 62 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Fold expansion


NEW Fold expansion is consistent across multiple collections from the same DATA donor Donor Fold Expansion 25 Collection 1 20 • Donors had slightly differential levels Collection 2 of expansion but were overall within 15 Collection 3 a consistent and predictable range 10 • Donors had consistent expansion 5 across multiple collections 0 Donor 1 Donor 2 Donor 3 63 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Fold Expansion


NEW DATA Gene editing efficiency is donor-dependent but consistent across collections 100 75 Pre-Purification CD3 KO and B2M 50 KO is donor-dependent 25 ⎯ Donor 1 and Donor 3 0 • ~80-90% (CD3 KO) Donor 1 Donor 1 Donor 2 Donor 3 • ~63-67% (B2M KO) ⎯ Donor 2 100 • ~68-75% (CD3 KO) Collection 1 80 Collection 2 • ~57-60% (B2M KO) 60 Collection 3 40 20 0 Donor 1 Donor 2 Donor 3 64 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. B2M KO (%) Pre-Purification CD3 KO (%) 84.8 65.6 64.8 85.9 67.7 84.4 57.4 58.9 60.4 67.6 63.8 63.3


NEW Final product phenotype is donor-dependent but consistent across multiple DATA collections Final Product CD8 Phenotype Final Product CD8 Phenotype 100 T EFF T EM T CM T SCM 50 0 65 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Donor 1, C1 Donor 1, C2 Donor 1, C3 Donor 2, C1 Donor 2, C2 Donor 2, C3 Donor 3, C1 Donor 3, C2 Donor 3, C3 % Frequency of subset


NEW Final product potency is donor-dependent but consistent for an DATA individual donor In Vivo Potency 150 100 50 0 P-BCMA-ALLO1 Products • There is donor-dependent variability for in vivo anti-tumor potency ⎯ This potency is relatively consistent with repeat donor collections and productions ⎯ Most variability in potency over repeat collections is due to changes in process/manufacturing 66 © 2024 Poseida Therapeutics, Inc. All Rights Reserved. Normalized Tumor AUC (% of PBS control)


Poseida’s manufacturing platform, used across all products, delivers T -rich SCM products with high purity Manufacturing T Cell Isolation • Production process Non-viral Gene Editing Allogeneic dCas9 with preserves T phenotype SCM CAR-T Cell Selection and manufacturing process right gRNA Expansion with Booster • Nearly all CAR-carrying enhanced with Booster dCas9 with Molecule cells Molecule technology to left gRNA ONE Purification deliver high yields • “On demand” delivery to LEUKOPAK Fill/finish site of care Storage in Inventory ONE HEALTHY DONOR ~100 DOSES P-BCMA-ALLO1 interim Phase I study data presented at IMS 2024 illustrates our manufacturing capability, using product from 7 manufacturing lots and 6 different qualified donors Poseida Data on File 67 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Future manufacturing platform enhancement opportunities Donor screening data is a ripe Gene editing is the most sensitive Poseida manufacturing processes space for cellular analysis via and critical element of the to date have used static expansion artificial intelligence. Advances in manufacturing process. flasks. Dynamic bioreactor this space can create a faster and Advances in electroporation unit environments and Booster more economical way to assess operations can improve editing, Molecule enabling technology potential donors. reduce the need for later have the potential to unlock depletion, and improve cell significantly higher yields, which health throughout the process. results in lower cost of goods and a smaller required pool of donors. 68 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Concluding remarks Kristin Yarema, PhD President & CEO


Strong partnerships with Roche and Astellas validate allogeneic platform and fund programs • $50 million upfront plus up to $550 • Deal worth up to $6 billion in million, plus royalties aggregate value, plus royalties • Currently three heme malignancy • Combines Poseida allogeneic platform collaboration programs with Astellas technology for up to two TM ‘convertibleCARs ’ for solid tumors • $80 million in milestone payments earned to date in 2024 • Follows an earlier $50 million equity investment in Poseida More than $400M generated through external partnership payments, upfronts and milestones over the past three years 70 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Poseida’s path to value creation in allogeneic cell therapy Presently heading into our second growth horizon Disrupt Cell Extend Therapy Approach Build Foundation DELIVER FOR PATIENTS DRIVE VALUE • Stream assets from allogeneic CAR- VALIDATE PLATFORM T product engine SCM • Enter autoimmune disease space • Advance non-viral allogenic CAR- • Launch new cell therapy platforms • Deepen and extend pharma T assets in the clinic for greater reach (CAR-TCR and SCM partnerships beyond) ― P-BCMA-ALLO1 in Phase 1b; • Grow wholly-owned asset pipeline RMAT designation • Manufacture high volume, low • Refine next-generation tools & COGS products at scale ― 3 clinical stage programs technologies across liquid & solid tumors • Commercialize partnered and own • Further strengthen manufacturing, assets that have strong value • Establish partnerships with Roche healthy donor competencies propositions and Astellas • Manufacture GMP product in-house 71 © 2024 Poseida Therapeutics, Inc. All Rights Reserved.


Thank You To our patients, partners and dedicated Poseida teams for supporting our bold mission to redefine the future of cell therapy for life-threatening cancers and autoimmune diseases


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Nov. 14, 2024
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