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): June 1, 2019
Bellicum Pharmaceuticals, Inc.
(Exact name of registrant as specified in its charter)
Delaware | 001-36783 | 20-1450200 | ||
(State or other jurisdiction of incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||
2130 W. Holcombe Blvd., Ste. 800 Houston, TX | 77030 | |||
(Address of principal executive offices) | (Zip Code) | |||
Registrant’s telephone number, including area code: 832-384-1100
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligations 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 $0.01 per share | BLCM | The Nasdaq Global 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 x
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. x
In this report, “we,” “us” and “our” refer to Bellicum Pharmaceuticals, Inc.
Item 7.01 Regulation FD Disclosure.
On June 1, 2019, we issued a press release announcing updated safety and activity data for BPX-601 from a Phase 1/2 study in patients with metastatic pancreatic cancer expressing prostate stem cell antigen. A copy of the press release is attached hereto as Exhibit 99.1.
An updated company slide presentation, which may be given at meetings with institutional investors or analysts, is attached hereto as Exhibit 99.2.
The information contained in this Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1 and 99.2, is being furnished pursuant to Item 7.01 and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and it shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or under the Exchange Act, whether made before or after the date hereof, except as expressly set forth by specific reference in such filing to this item of this report.
By filing this Current Report on Form 8-K, including Exhibits 99.1 and 99.2, and furnishing this information, we make no admission as to the materiality of any information in this report. The information contained in this report is intended to be considered in the context of our filings with the SEC and other public announcements that we make, by press release or otherwise, from time to time. We undertake no duty or obligation to publicly update or revise the information contained in this report, although we may do so from time to time as our management believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases or through other public disclosure.
Item 8.01 Other Events.
On June 1, 2019, we presented a poster containing updated data from the aforementioned BPX-601 Phase 1/2 study at the 2019 American Society for Clinical Oncology (“ASCO”) Annual Meeting. A copy of the poster, titled Ligand-Inducible, Prostate Stem Cell Antigen (PSCA)-Directed GoCAR-T® Cells in Advanced Solid Tumors: Preliminary Results with Cyclophosphamide (Cy) ± Fludarabine (Flu) Lymphodepletion (LD), is attached hereto as Exhibit 99.3. This poster may be presented at future meetings with institutional investors or analysts. We previously presented a draft version of this poster, attached hereto as Exhibit 99.4, at meetings with institutional investors.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. | Description | |
99.1 | ||
99.2 | ||
99.3 | ||
99.4 | ||
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.
Bellicum Pharmaceuticals, Inc. | ||||||
Dated: June 3, 2019 | By: | /s/ Richard A. Fair | ||||
Richard A. Fair | ||||||
President and Chief Executive Officer | ||||||
(Principal Executive Officer) | ||||||
Exhibit 99.1
Bellicum Pharmaceuticals Provides Interim Data for BPX-601 in
Patients with Metastatic Pancreatic Cancer for Presentation at ASCO
Annual Meeting
Data provides further evidence that GoCAR-T® technology boosts expansion and persistence of therapeutic T cells in patients
T cell expansion and persistence greater in patients who received lymphodepletion with cyclophosphamide plus fludarabine (Flu/Cy) compared to Cy alone
Of 13 patients evaluable for efficacy treated with BPX-601 and a single dose of rimiducid, 8 (62%) achieved stable disease, including 3 with tumor shrinkage of 10% to 24%
Adverse events were generally consistent with those experienced by advanced cancer patients undergoing cytotoxic chemotherapy and other cancer immunotherapies
HOUSTON, June 1, 2019 -- Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, today announced updated safety and activity data for BPX-601 from a Phase1/2 study in patients with metastatic pancreatic cancer expressing prostate stem cell antigen (PSCA). The most recent cohort of patients enrolled incorporated a standard lymphodepletion conditioning regimen consisting of fludarabine/cyclophosphamide (Flu/Cy) prior to receiving BPX-601 GoCAR-T cells. Updated data from this study-including patients from this Flu/Cy cohort-will be presented during the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting on June 1, 2019.
BPX-601, the company’s first GoCAR-T® product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC, inducible MyD88/CD40 via administration of rimiducid, is designed to provide a powerful boost to T cell proliferation and persistence and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta.
“These updated results in patients with advanced pancreatic cancer showed that more intense lymphodepletion with Flu/Cy resulted in increased BPX-601 CAR-T cell expansion and prolonged persistence in patients treated with single-dose rimiducid,” said Carlos R. Becerra, M.D., lead study investigator, oncologist, and medical director of the Innovative Clinical Trials Center at Baylor University Medical Center at Dallas. “Evidence of biological activity and stable disease was observed in this ongoing trial in these heavily pretreated patients who desperately need additional treatment options. We consider these results highly encouraging.”
“I am excited that additional data from our BPX-601 trial continue to support the potential of our GoCAR-T technology platform. Our data presentation at ASCO supports the safety and early clinical activity of BPX-601, and provides further evidence of the impact of our technology in driving the expansion and persistence of T cells in patients,” said Rick Fair, President and CEO of Bellicum Pharmaceuticals. “We have initiated the next step in the study to enroll an additional cohort to evaluate repeat rimiducid dosing to re-activate iMC over time, which is intended to deepen and extend the treatment effect. Initial results from this cohort are expected in late 2019.”
Study Overview and Results
1
Exhibit 99.1
This Phase 1/2 trial has been designed to enroll patients with PSCA-positive pancreatic cancer to assess the safety, biologic and clinical activity of BPX-601. As of April 23, 2019, the data cut-off date for the current analysis, 18 patients have been treated with BPX-601. The initial 13 patients received BPX-601 following Cy lymphodepletion, and 5 patients in the latest cohort received BPX-601 following Flu/Cy lymphodepletion. Four patients did not receive rimiducid, and 14 patients received a single dose of rimiducid approximately one week following BPX-601. Following is a summary of the results to date:
• | Peak Vector Copy Number (VCN) of T cells was enhanced by the administration of rimiducid to activate iMC, increasing cell dose, and lymphodepletion with Flu/Cy |
• | Rimiducid-dependent increase in serum cytokines and chemokines observed in most patients, particularly those in the Flu/Cy cohort |
• | T cell persistence of >3 weeks was observed in nine of 17 patients (53%) with a minimum of 28 days of follow-up samples, including all 5 patients (100%) who received Flu/Cy |
• | Administration of BPX-601 followed by single-dose rimiducid was well tolerated with no dose-limiting toxicities |
• | Adverse Events (AEs) were generally consistent with those experienced by advanced cancer patients undergoing cytotoxic chemotherapy and other cancer immunotherapies |
◦ | All 18 patients treated with BPX-601 reported at least 1 AE. The most frequent AEs regardless of causality were febrile neutropenia (33%), fatigue (28%), neutropenia (28%), pyrexia (28%), dysuria (22%), hematuria (22%) and nausea (22%). |
• | The majority of AEs related to BPX-601/rimiducid were mild to moderate in intensity and resolved with or without supportive care. New treatment related adverse events in the Flu/Cy cohort included: |
◦ | One patient experienced Grade 2 cytokine release syndrome (CRS) post-rimiducid infusion, received treatment with a single infusion of IV tocilizumab, and the event resolved the same day |
◦ | One patient experienced Grade 2 encephalopathy post-rimiducid infusion with no concomitant CRS. Symptoms resolved with corticosteroids within 1 week |
◦ | Four patients experienced Grade 1-3 urologic toxicity (dysuria, hematuria, cystitis). Symptoms in all patients resolved with standard supportive care (analgesics, anticholinergics, bladder irrigation) |
• | Of 13 efficacy-evaluable patients treated with BPX-601 and a single dose of rimiducid, 8 patients (62%) had stable disease, and 3 patients had tumor shrinkage of 10% to 24% |
• | With median duration of follow-up of 9.1 weeks (range: 2.9 - 30.3 weeks), the median time to follow-on cancer therapy in patients who received subsequent therapy was 16.6 weeks (range: 5.6 - 30.3 weeks) |
• | In the Flu/Cy cohort, 2 patients with at least the median follow-up of 9.1 weeks had a time to next treatment of >22 weeks which was ongoing at the time of the data cutoff |
The poster, titled Ligand-Inducible, Prostate Stem Cell Antigen (PSCA)-Directed GoCAR-T® Cells in Advanced Solid Tumors: Preliminary Results with Cyclophosphamide (Cy) ± Fludarabine (Flu) Lymphodepletion (LD), may be found on the Bellicum website under Abstracts and Presentations.
About BPX-601
BPX-601, the company’s first GoCAR-T® product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for solid tumors expressing prostate stem cell antigen (PSCA), including pancreatic, gastric, and prostate cancers.
2
Exhibit 99.1
About Bellicum Pharmaceuticals
Bellicum is a clinical stage biopharmaceutical company striving to deliver cures through controllable cell therapies. The company’s next-generation product candidates are differentiated by powerful cell signaling technologies designed to produce more effective CAR-T and allogeneic T cell therapies. Bellicum’s lead GoCAR-T® candidate, BPX-601, is designed to be a more efficacious CAR-T cell product capable of overriding key immune inhibitory mechanisms. Bellicum’s rivo-cel product candidate is an allogeneic polyclonal T cell therapy that has shown promising clinical trial results in reducing leukemia relapse after a stem cell transplant. More information can be found at www.bellicum.com.
Forward-Looking Statement
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Bellicum may, in some cases, use terms such as “potential,” “continue,” “designed,” “expects,” “plans,” “intends,” “may,” “will,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: our research and development activities relating to BPX-601, possible ranges of application and potential safety and curative effects in the treatment of diseases, including as compared to other treatment options and competitive therapies, and the timing and speed of enrollment in clinical trials for BPX-601. Various factors may cause differences between Bellicum’s expectations and actual results as discussed in greater detail under the heading “Risk Factors” in Bellicum’s filings with the Securities and Exchange Commission, including without limitation our quarterly report on Form 10-Q for the three months ended March 31, 2019 and our annual report on Form 10-K the year ended December 31, 2018. Any forward-looking statements that Bellicum makes in this press release speak only as of the date of this press release. Bellicum assumes no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
Source: Bellicum Pharmaceuticals
Contacts:
Investors:
Robert H. Uhl
Managing Director
Westwicke IR
858-356-5932
Robert.uhl@westwicke.com
Media:
Jim Heins
Senior Vice President
Westwicke PR
203-682-8251
james.heins@icrinc.com
###
3
Investor Presentation Striving to deliver cures through controllable cell therapy June 2019
Forward Looking Statement This presentation contains estimates, projections and other forward-looking statements, concerning, among other things: our research and development activities relating to our CaspaCIDe® (“iC9”), GoCAR-T ® (incorporating “iMC”) and related technologies; our product candidates including rivo-celTM (previously BPX-501), BPX-601, BPX-603, BPX-802, and rimiducid; the effectiveness of our CaspaCIDe and GoCAR-T programs and their possible range of application and potential curative effects and safety in the treatment of diseases, including as compared to other treatment options and competitive therapies; the success of our collaborations with academic and commercial partners; the timing, progress of enrollment and success of our clinical trials; and the timing of potential European marketing authorization applications for rivo-cel and rimiducid. Our estimates, projections and other forward-looking statements are based on our management's current assumptions and expectations of future events and trends, which affect or may affect our business, strategy, operations or financial performance. Although we believe that these estimates, projections and other forward-looking statements are based upon reasonable assumptions, they are subject to numerous known and unknown risks and uncertainties and are made in light of information currently available to us. Many important factors, in addition to the factors described in this presentation, may adversely and materially affect our results as indicated in forward-looking statements. All statements other than statements of historical fact are forward-looking statements. Estimates, projections and other forward-looking statements speak only as of the date they were made, and, except to the extent required by law, we undertake no obligation to update any forward-looking statement. These statements are also subject to a number of material risks and uncertainties that are described more fully in Bellicum’s filings with the Securities and Exchange Commission, including without limitation our annual report on Form 10-K for the year ended December 31, 2018 and our quarterly report on Form 10-Q for the period ended March 31, 2019. 1
Investment Summary Rivo-cel GoCAR-T Pipeline Allogeneic polyclonal T-cells for hematologic Controllable CAR-T cells designed to optimize malignancies and inherited blood disorders (+HSCT) efficacy and safety European pediatric opportunity clinically de-risked BPX-601 GoCAR-T promising early clinical data ▪ 249 patients enrolled in Phase 1 / 2 study ▪ Phase 1 / 2 study enrolling in pancreatic cancer ▪ Late interim results presented at ASH in Dec. 2018 trend ▪ Initial safety data on 18 pancreatic cancer patients presented at toward meeting primary endpoint ASCO in June 2019 indicate attractive safety profile and early clinical activity ▪ Expect topline data in 1H 2019; MAA filings in 2H 2019 ▪ European HQ and leadership team in place for ▪ Trial amendment for repeat activation molecule administration to commercialization prep enhance potential clinical response Global trial underway to broaden label Two dual-switch GoCAR-T candidates to IND in 2019 ▪ Enrolling Phase 2/3 THRIVE study in AML and MDS in ▪ BPX-603 targeting HER2 antigen in solid tumors patients 12+ years old ▪ BPX-802 targeting liquid tumors, target antigen TBA Cash, cash equivalents, restricted cash and investment securities of $78.1MM as of March 31, 2019; Cash runway through 2019 2
Development Pipeline: Rivo-cel and GoCAR-T Controllable cell therapies that may represent major advances in liquid and solid tumors PRODUCT CANDIDATE DISCOVERY CLINICAL PROOF OF CONCEPT PIVOTAL CLINICAL STATUS Rivo-cel Topline data: Rivo-cel iC9 E.U.: Pediatric Leukemias, Lymphomas, and Inherited blood disorders (+allo-HSCT) (BPX-501) Ph 2 results in 1H 2019 (BPX-501) Allogeneic Polyclonal T-cells 12+ Years AML + MDS (+allo-HSCT) – THRIVE Enrolling patients in pivotal Ph 2/3 BPX-601 Data updates in 1H and GoCAR-T Pancreatic, Gastric, & Prostate Cancers 2H 2019 from ongoing Ph PSCA 1/2 trial BPX-603 IND filing 1H 2019; initiate iC9 Solid Tumors GoCAR-T clinical trial 2H 2019 HER-2 BPX-802 iC9 GoCAR-T Liquid Tumors IND filing 2H 2019 Target TBA In planning 3
Technology Overview 4
Most Cell Therapies Only Controlled Before Infusion Limited ability to expand a narrow therapeutic window On Target / Off Tumor GvHD TOXICITY CRS Neurotoxicity BEFORE INFUSION AFTER INFUSION CONTROLLED UNPREDICTABLE Anergy Collect white Genetic Patient blood cells modification infusion Insufficient peak dose Lack of persistence POOREFFICACY 5
Bellicum Platform Designed to Enable Control After Infusion Would provide physicians the ability to expand the therapeutic window in each patient iMC ACTIVATION switch to activate immune cells and modulate the iMC tumor micro- environment Potential for BEFORE INFUSION AFTER INFUSION CONTROLLED CONTROLLED Improved Benefit / Risk CaspaCIDe Collect white Genetic Patient iC9 blood cells modification infusion SAFETY switch to eliminate toxic cells 6
Chemical Induction of Dimerization (“CID”) Molecular Switch Platform Rimiducid infusion activates signaling pathways to control T-cell function 1 VECTOR APPLICATION SPECIFIC Monomeric = Dimerized = Viral transduction ACCESSORY PROTEINS 1 Inactive Proteins Active Proteins transfers the DNA 3 from a vector into the BINDING target cell nucleus. DOMAIN 2 Vector-derived DNA directs expression of CID and accessory SIGNALING proteins. DOMAIN SIGNAL CASCADE 3 Rimiducid dimerizes the CID proteins, thus 2 CID PROTEINS turning on the signal cascade. Signal Caspase-9 (“iC9”) MyD88 and CD40 (“iMC”) Result Apoptosis (cell death) T-cell activation, proliferation & survival 7
GoCAR-T Pipeline 8
GoCAR-T: Differentiated Approach to Cell Therapy Current Challenges in Cell Therapy GoCAR-T Benefits Limited efficacy in solid tumors Potential for enhanced efficacy in solid tumors via ▪ Inadequate cell proliferation and iMC signaling persistence to sustain efficacy ▪ MyD88 and CD40 are superior co-stimulatory molecules ▪ Inability to overcome immune suppressive with potential for greater cell expansion and persistence factors in tumor microenvironment (TME) ▪ Modulates the tumor microenvironment, overriding common inhibitory pathways (PD-1, PGE2, TGF-β) ▪ Enhances host immune activity by inducing pro- inflammatory cytokines and chemokines Potential safety issues with Potential for enhanced safety more potent approaches ▪ iMC provides control over timing and frequency of co- activation ▪ CaspaCIDe capable of eliminating a majority of CAR-T cells to manage acute toxicities 9
BPX-601 GoCAR-T Targeting PSCA Product Summary Unmet Need High unmet need in solid tumors expressing ▪ Attractive first-in-class solid tumor CAR-T opportunity Prostate Stem Cell Antigen (PSCA) ▪ First-in-human experience with iMC Annual Annual % Expressing Incidence Deaths (US) PSCA ▪ Initial Phase 1 results presented in June 2019 continue to (US) demonstrate: Pancreatic 55k 44k ~60% - Safety - iMC-driven T cell activation Prostate 165k 29k 75-90% - Biologic activity ▪ Phase 1 enrollment ongoing Gastric 26k 11k 76-89% Incidence and annual deaths: Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. PSCA expression: Argani et al, Cancer Res 2001; Reiter et al., PNAS 1998; Abate-Daga et al, HGT 2014; Data on file 10
BPX-601: Phase 1 Trial Progression BP-012 trial in relapsed/refractory pancreatic, gastric, and prostate cancers Dose Full Efficacy Optimized Lead-in Escalation Conditioning Regimen Dose escalation designed conservatively to evaluate safety Patient Population 2L to 6L Pancreatic 2L Pancreatic • Partial conditioning with Cytoxan monotherapy • Single dose of rimiducid to BPX-601 Dose 1.25 1.25, 2.5, 5.0 5.0 activate iMC x106 cells/kg @ Day 0 Recently evaluated impact of full Cytoxan 0.5g/m2 conditioning Cytoxan 1g/m2 Conditioning Fludarabine 30mg/m2 • Standard Flu/Cy regimen @ Day -3 @ Days -5, -4, -3 • Single dose of rimiducid to activate iMC Rimiducid Dose Scheduled Repeat Next step: efficacy-optimized None Single Dose Single Dose @ Day 7 Dosing regimen • Standard Flu/Cy regimen plus Status Enrolled & Presented Pending repeat rimiducid dosing • Data presentation: late 2019 ClinicalTrials.gov Identifier: NCT02744287 11
BPX-601: No Dose Limiting Toxicities Observed Data presented at ASCO 2019 ▪ No dose limiting toxicities were observed Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B All Patients Patients, n (%) n = 3 n = 3 n = 3 n = 4 n = 5 N = 18 Any AE 3 (100) 3 (100) 3 (100) 4 (100) 5 (100) 18 (100) ▪ Adverse Events (AEs) were generally Any SAE 2 (67) 1 (33) 0 3 (75) 4 (80) 10 (56) consistent with cytotoxic Grade 3 & 4 TRAEs 0 0 0 0 1 (20) 1 (<1) chemotherapy or other cancer AEs in >15% of all patients, n (%) immunotherapies Febrile neutropenia 0 0 0 2 (50) 4 (80) 6 (33) Fatigue 2 (67) 1 (33) 0 2 (50) 0 5 (28) ▪ AEs related to BPX-601/rimiducid Neutropenia 0 0 0 1 (25) 4 (80) 5 (28) included: Pyrexia 0 0 1 (33) 2 (50) 2 (40) 5 (28) Dysuria 0 0 0 0 4 (80) 4 (22) Hematuria 0 0 0 0 4 (80) 4 (22) ▪ One case of Grade 2 cytokine Nausea 2 (67) 0 0 0 2 (40) 4 (22) release syndrome (CRS) Abdominal pain 1 (33) 1 (33) 0 0 1 (20) 3 (17) Abdominal pain upper 0 1 (33) 1 (33) 1 (25) 0 3 (17) ▪ One case of Grade 2 Anemia 0 0 0 1 (25) 2 (40) 3 (17) encephalopathy Back pain 1 (33) 1 (33) 0 1 (25) 0 3 (17) Blood bilirubin increased 0 0 0 1 (25) 2 (40) 3 (17) Hypotension 0 0 2 (67) 1 (25) 0 3 (17) ▪ Four cases of Grade 1-3 urologic toxicity (dysuria, hematuria, cystitis) Becerra et al, ASCO 2019 12
BPX-601: iMC-Driven T Cell Expansion & Persistence Flu/Cy Lymphodepletion Results in Increased BPX-601 Cell Expansion and Persistence Cy Flu/Cy ▪ Peak expansion 4.9-fold higher in Flu/Cy cohort vs Cy alone cohorts ▪ Persistence improves with: ▪ Administration of rimiducid to activate iMC ▪ Higher cell dose ▪ Lymphodepletion with Flu/Cy Becerra et al, ASCO 2019 Cohort 0 Cohort 3 Cohort 4 1.25 x 106 cells/kg (Cy) 1.25 x 106 cells/kg + Rim (Cy) 2.5 x 106 cells/kg + Rim (Cy) * Data points represent the mean log VCN for each cohort and the dotted red line represents rimiducid administration at Day 7; † Patient 3 in cohort 5A did not have data for time points beyond Cohort 5A† Cohort 5B Day 4 and thus is not included in the summary of cell persistence. 6 6 5.0 x 10 cells/kg + Rim (Cy) 5.0 x 10 cells/kg + Rim (Flu/Cy) ALC, absolute lymphocyte count; Cy, cyclophosphamide; Flu, fludarabine; LD, lymphodepletion; LOQ, limit of quantitation; pts, patients; Rim, rimiducid; VCN, vector copy number. 13
BPX-601: Evidence of Anti-Tumor Activity ▪ 8 (62%) of 13 evaluable patients treated with BPX- 601 and single-dose rim achieved stable disease; 3 had tumor shrinkage of 10-24% ▪ With 9.1 weeks median follow-up (range: 2.9-30.3), median time to next cancer therapy in patients that received subsequent treatment was 16.6 weeks (range 5.6-30.3) ▪ In Flu/Cy cohort, 2 patients with >median follow-up had time to next treatment * Right arrow cap indicates ongoing treatment-free interval; † Patient withdrew consent for further follow-up; ‡ Patient 2 was not efficacy evaluable due to non-measurable disease at baseline. >22 weeks (ongoing) PD, progressive disease; pseudo, pseudoprogression; SD, stable disease. Becerra et al, ASCO 2019 14
BPX-603 Dual Switch GoCAR-T Targeting HER2 Product Summary Unmet Need 1 + ▪ HER2 is a validated tumor antigen and is expressed Indication Incidence HER2 5-year OS (Stage IV)1 on numerous solid tumors with high unmet need Gastric 28,000 10-30%3 <20% ▪ Historical HER2 CAR-T studies have shown modest overall activity and off-tumor / on-target toxicity Colorectal 145,000 10%4 <15% ▪ BPX-603 may address these limitations Ovarian 22,000 20-30%5 <30% - iMC may increase cell proliferation & persistence, Uterine/ 61,000 50-80%6 14-69% modulate the TME, and enhance host immunity Endometrial - CaspaCIDe may mitigate treatment emergent toxicities Glioblastoma 12,000 20-30%2 <20% 1National Cancer Database, American Cancer Society, https://www.cancer.org, accessed 21 December 2018; 2Liu et al., Cancer Res 2004; 3Gravalos et al., Annals Oncol 2008; 4Tu et al., Exp Ther Med 2018; 5Berchuck et al., Cancer Res 1990, Bartlett et al., Brit J Cancer 1996; 6Grushko et al., Gynecologic Oncol 2008 15
Historical HER2 Studies: Modest Clinical Outcomes Study Properties Morgan, 2010 Ahmed, 2015 Feng, 2017 Ahmed, 2017 Hegde, 2019 Construct 4D5-28-BB-z FRP5-28-z Her2-BB-z FRP5-28-z FRP5-28-z Indication(s) Metastatic colon Sarcomas CCA and PCa GBM Sarcomas Patient number 1 19 11 17 10 HER2 expression ≥2+ (IHC) ≥1+ (IHC) >50% positive ≥1+ (IHC) ≥1+ (IHC) CAR-T dose 1010 104 - 108 106 106 - 108 108 CAR-T expansion NE Negligible >1,000 copies Negligible >10,000 copies Toxicity Lung reactivity No DLTs Mild AEs Mild AEs Mild AEs Outcome Grade 5 toxicity 1 PR 1 PR 1 PR 2 CR Total Responses 2 CR, 3 PR, 5/58 (8.6% ORR) 16
BPX-603 Pre-Clinical Studies Demonstrate Potential Clinical Benefits Tumor growth Survival 1 0 9 1 0 0 ) C o n tr o l T c e lls r s l / 1 0 8 B P X -6 0 3 + V e h a 2 v 7 5 i m v c B P X -6 0 3 + R im / 7 r s + 1 0 u / s HER2 A549 p ( t 5 0 n e 6 1 0 e c Lung Carcinoma c n r a e i 2 5 5 P 4 d 1 0 (1x10 T cells) a R 1 0 4 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 D a y s p o s t-T c e ll in je c tio n D a y s p o s t-T c e ll in je c tio n 1 0 9 1 0 0 ) C o n tr o l T c e lls r 8 s 1 0 l / B P X -6 0 3 + V e h a 2 v 7 5 i m 7 v c 1 0 B P X -6 0 3 + R im / r s + u / s HER2 OE19 p 6 ( 1 0 t 5 0 n e e c 5 Esophageal Carcinoma c n 1 0 r a e i 2 5 P 6 d 4 (5x10 T cells) a 1 0 R 1 0 3 0 0 1 0 2 0 3 0 4 0 5 0 0 1 0 2 0 3 0 4 0 5 0 D a y s p o s t T c e ll in je c tio n D a y s p o s t-T c e ll in je c tio n 17
RIVO-CEL 18
Rivo-cel: Opportunity To Transform Treatment Paradigm Current HSCT Treatment paradigm Potential Future HSCT Treatment Paradigm HLA-Matched Toxicity and likelihood MRD Related Donor (MRD) of match Alternative Alternative Alternative HLA-Matched Unrelated Donor (MUD) Alternative rivo-cel MUD + Other Donor Options Haplo HSCT (Haplo and other) 1Other includes HLA mismatched and umbilical cord blood. 19
BP-004 Study: Basis for European Pediatric Approval Phase 1/2 study of rivo-cel in pediatric patients following TCR 훼β depleted allo-HSCT High risk pediatric αβ T-cell and B-cell Rimiducid for patients who malignancies and non- depleted haplo-HSCT Rivo-cel develop visceral GvHD or are malignant disorders without GvHD Prophylaxis refractory to SOC treatment Enrolled Populations Outcomes Rivo-cel: N = 249 (EU and US Patients) ▪ Event-free survival at 180 days (regulatory endpoint) Malignant (N = 117) Non-Malignant (N = 132) - TRM/NRM, severe GvHD, and Diagnosis Diagnosis life-threatening infections Acute lymphocytic leukemia (ALL) Primary Immune Deficiencies ▪ Progression-free survival Acute myeloid leukemia (AML) β Thalassemia Major ▪ Disease status Other Other Erythroid Disorders Rimiducid: Bone Marrow Failure Disorders ▪ GvHD response TRM, transplant-related mortality; NRM, non-relapse mortality; GvHD, graft versus host disease; SOC, standard of care; 20 HSCT, hematopoietic stem cell transplantation. ClinicalTrials.gov Identifiers: NCT01744223, NCT02065869.
Rivo-cel Interim Results Trend Towards Meeting Primary Endpoint Interim six-month event-free survival comparable to MUD HSCT Event Free Survival at 180 days ▪ C-004 is an observational trial of pediatric patients with malignant (67%) or non-malignant (33%) disease who underwent a MUD HSCT ▪ Non-inferiority of rivo-cel EFS N= 166, Events = 15, EFS 90.9% at 180 days to MUD HSCT is (95% CI 86.5-95.3%) required for EMA approval N=91, Events = 11, EFS 87.7% ▪ Full analysis with statistical (95% CI 80.8-94.5%) comparisons of patients who received rivo-cel or a MUD HSCT planned for 2019 EFS, event free survival; MUD, matched unrelated donor; HSCT, Hematopoietic Stem Cell Transplantation Data presented at 60th ASH Annual Meeting – December, 2018 21
Rivo-cel: High Rates of Disease-Free and Overall Survival Interim survival results With median follow-up of N= 166, Events = 9, Overall Survival 94.4% 20.3 months (0.5 – 47.4 (95% CI 90.8-98%) months): ▪ Relapse-free survival 82.9% in malignant patients ▪ Disease-free survival 95.2% in non- malignant patients 22
Rivo-cel: High Rates of GvHD Response to Rimiducid Interim results of response in patients refractory to standard of care treatment Methods & Evaluable Population Efficacy Results Translational Results Patients who developed visceral Best overall response of 70% Reduction in rivo-cel serum levels GvHD or were refractory to SOC 7 days post-rimiducid observed in all patients receiving treatment were eligible to receive rimiducid1 ≥1 dose (up to 3 at 48 hour ▪ 9 CR and 7 PR intervals) of rimiducid (0.4 mg/kg) Rimiducid eliminates the most ▪ Median time to response of 1 day highly activated rivo-cel T cells Of 238 GvHD-evaluable patients: (1 - 4 days) which express the highest level of Four patients in PR or not evaluable iC92, leaving remaining cells to ▪ 35.7% (85/238) experienced any re-expand grade acute or chronic GvHD at day 7 achieved CR within 30 days post-rimiducid ▪ 79% (11/14) malignant patients ▪ 28.2% (24/85) of patients with receiving rimiducid remain GvHD received rimiducid relapse free GvHD: acute graft versus host disease; SOC, Standard of Care; PR, Partial Response; CR, Complete Response 1. N = 10 with translational data at time of interim. 2. Zhou et al. ASH 2018, a3496 23
THRIVE: Registrational Trial in Adults & Adolescents Phase 2/3 study of rivo-cel in intermediate and high risk AML & MDS in patients 12+ years old Phase II Phase III Arm A Patients ≥ 12 years αβ T cell and CD19+ B-cell-depleted haploidentical Cohort 1 † (n= 10) with intermediate stem cell transplantation plus rivo-cel (n = 84) Cohort and high risk AML R 3 x 106 rivo- Review or MDS* 1:1 cel cells/kgA Arm B (n= 168) Unmanipulated haploidentical stem cell transplantation plus post-transplant cyclophosphamide (n = 84) Primary Outcome Secondary Outcomes ▪ Graft-versus host disease and relapse-free ▪ Relapse free survival (RFS) survival (GRFS) at time from randomization ▪ Non-relapse mortality (NRM) Overall until Grade 3-4 acute GvHD, chronic GvHD ▪ Time to resolution of GvHD after requiring systemic immunosuppression, administration of rimiducid Survival disease relapse or death, whichever comes first A If dose level 1 exceeds the MTD, alternative dose levels (dose level -1: 1 x 106 BPX-501 cells/kg) will be explored † No GvHD prophylaxis will be given. Rimiducid will be administered to inactivate rivogenlecleucel (rivo-cel) in the event of GVHD not responsive to standard of care treatment Updated 8 Nov 2018. Clinicaltrials.gov identifier: NCT03699475 24
Rivo-cel Addresses Key Shortcomings Rivo-cel addresses shortcomings of stem cell transplants to treat hematological malignancies and inherited blood disorders Rivo-cel Target Market Matched Related Matched Unrelated Haplo and Rivo-cel Donor (MRD) Donor (MUD) Other +HSCT % of Current Market 25-30% ~50% ~20-25% Disease Relapse Infection GvHD Leading Causes of of Causes Leading Mortality and Morbidity and Mortality Likelihood to Find Donor Low Low-Medium High High Time to Short Long Short Short Identify Donor 25
Rivo-cel: Significant Market Opportunity Potential List Price Patient Population Market Opportunity Additional Opportunities Haplo/ European Initial market: Other: EU Pediatric* 0.4 Pediatric Cost (in thousands) Effectiveness $0.5-0.7 ▪ Geographic expansion TOTAL: 1.8 Analysis MUD: 1.4 billion ▪ U.S. Pediatric ▪ Asia $300- ▪ Patient population growth $400k US Next market: Haplo/ Adult & ▪ Expansion of HSCT Other: eligibility Adult & EU 1.1 Adolescent Market Pricing Adolescent Haplo/ AML/MDS Research Benchmarks Other: 1.4 ▪ Development in other AML/MDS* EU MUD: 4.9 malignancies (in thousands) US $3-4 MUD: 2.3 TOTAL: 9.7 billion *As of 2016. EBMT Transplant Activity Survey; CIBMTR Current Uses & Outcomes of HCT; internal company analysis Market share expectations represented by green (strong) and yellow (moderate) 26
Rivo-cel: Significant Opportunity for EU Pediatric Launch Pricing & Manufacturing & Demand Team Reimbursement Supply Chain ▪ Encouraging early ▪ Early payer market ▪ Robust manufacturing ▪ Efficient: KOL feedback research encouraging process developed ~75 transplant centers at target pricing represent ~80% of ▪ Compelling clinical ▪ Commercially opportunity value proposition ▪ Outstanding clinical experienced cell profile and strong therapy CMO ▪ Experienced: ▪ Broad and rapid health economics outstanding team in haplo donor ▪ High touch supply place with relevant availability chain & customer track record service solution being co-developed 27
Anticipated 2019 and 2020 Key Program Milestones 1H’19 2H’19 2020 Presentations of updated Phase 1 results Presentation of updated Phase 1 results Updated Phase 1 and (Flu/Cy regimen) at ASCO (repeat rimiducid dosing) Phase 2 results BPX-601 Amend BP-012 to allow for repeat dosing of rimiducid to reactivate iMC IND submission for BPX-603 First patient treated in BPX-603 BPX-603 Phase 1 data CAR-T Phase 1 trial PIPELINE BPX-802 Phase 1 data IND submission for BPX-802 Final analyses of BP-004 and MAA submissions for rivo-cel and Potential MAA Approval C/CP-004 trials rimiducid for pediatric patients Rivo-cel THRIVE Phase 2 data 28
Investment Summary Rivo-cel GoCAR-T Pipeline Allogeneic polyclonal T-cells for hematologic Controllable CAR-T cells designed to optimize malignancies and inherited blood disorders (+HSCT) efficacy and safety European pediatric opportunity clinically de-risked BPX-601 GoCAR-T promising early clinical data ▪ 249 patients enrolled in Phase 1 / 2 study ▪ Phase 1 / 2 study enrolling in pancreatic cancer ▪ Late interim results presented at ASH in Dec. 2018 trend ▪ Initial safety data on 18 pancreatic cancer patients presented at toward meeting primary endpoint ASCO in June 2019 indicate attractive safety profile and early clinical activity ▪ Expect topline data in 1H 2019; MAA filings in 2H 2019 ▪ European HQ and leadership team in place for ▪ Trial amendment for repeat activation molecule administration to commercialization prep enhance potential clinical response Global trial underway to broaden label Two dual-switch GoCAR-T candidates to IND in 2019 ▪ Enrolling Phase 2/3 THRIVE study in AML and MDS in ▪ BPX-603 targeting HER2 antigen in solid tumors patients 12+ years old ▪ BPX-802 targeting liquid tumors, target antigen TBA Cash, cash equivalents, restricted cash and investment securities of $78.1MM as of March 31, 2019; Cash runway through 2019 29
Ligand-Inducible, Prostate Stem Cell Antigen (PSCA)-Directed GoCAR-T® Cells in Advanced Solid Tumors: Abstract #2536 Preliminary Results With Cyclophosphamide (Cy) ± Fludarabine (Flu) Lymphodepletion (LD) Carlos R. Becerra,1 Gulam Manji,2 Dae Won Kim,3 Olivia Gardner,4 Aditya Malankar,4 Joanne Shaw,4 Devin Blass,4 Xiaohui Yi,4 Aaron Foster,4 Paul Woodard4 1Baylor University Medical Center, Dallas, TX; 2Columbia University, New York, NY; 3Moffitt Cancer Center, Tampa, FL;4 Bellicum Pharmaceuticals, Inc., Houston, TX. • All BPX-601-treated patients reported at least 1 adverse event (AE); the most common AEs (in >20% of all patients) • As shown in Figure 5, following single-dose rimiducid on Day 7: • With 9.1 weeks median duration of follow-up (range: 2.9–30.3 weeks), the median time to follow-on cancer therapy in BP-012 (NCT02744287) Study Design Figure 3. regardless of causality, LD regimen, or BPX-601 dose were febrile neutropenia (33%), fatigue (28%), neutropenia (28%), patients who received subsequent therapy was 16.6 weeks (range: 5.6–30.3 weeks; Figure 7) --Rimiducid-dependent elevations in IL-2, IL-5, IL-6, and IP-10 were observed in most patients, particularly those in pyrexia (28%), dysuria (22%), hematuria (22%), and nausea (22%) (Table 2) 6 BACKGROUND Single infusion BPX-601 cell dose cohort 5B, and correlated with cell expansion • At the highest cell dose (5.0 x 10 cells/kg) after Flu/Cy LD followed by a single rimiducid dose at Day 7: escalation (3+3) based on safety • As of the data cut off, no BPX-601 dose limiting toxicities were observed --2 patients with at least 9.1 weeks of follow-up had a time to next treatment of >22 weeks which was ongoing at the time • Inducible MyD88/CD40 (iMC) is a novel co-activation switch comprised of two synergistic signaling domains regulated by --Similar rimiducid-dependent increases in IL-8, G-CSF, MCP-1, MIP-1α, and MIP-1β were also observed (data not shown) 1 Cohort 5A: • Nine patients (50%) reported treatment-related AEs (TRAEs); dysuria (n = 4), hematuria (n = 4), pyrexia (n = 3), of the data cutoff the synthetic small-molecule ligand, rimiducid (Figure 1) 6 5.0 x 10 cells/kg and hypotension (n = 2) were reported by ≥2 patients --Increased serum IP-10 was indicative of prior IFN-γ production and, together with increased serum TNF-α, supports • iMC contains a rimiducid-binding domain (two FK506-binding proteins) coupled with the signaling components from after Cy LD --1 patient who had previously received 2 lines of systemic therapy (patient 2) had stable disease that was ongoing at All TRAEs were mild/moderate except for Grade 3 hematuria and Grade 3 groin pain reported by 1 patient; T cell activation in response to activation of iMC by rimiducid MyD88 and CD40, which play critical roles in initiation and maintenance of an innate and adaptive immune response1 Cohort 5B: • 6 months 5.0 x 106 cells/kg no Grade 4 TRAEs were reported --Increased BPX-601 dose was associated with overall increased serum cytokine and chemokine levels • Transcription factor activation via the MyD88 and CD40 signaling domains leads to upregulation of proinflammatory after Flu/Cy LD Cohorts Phase 2: 1 • Ten patients (56%) reported SAEs; febrile neutropenia was the only SAE reported by >1 patient (n = 5) cytokines and type I interferons, which promote proliferation, activation, and survival of immune cells, including T cells 3, 4, 5: multi-arm dose • Limited peripheral cytokine changes were observed when BPX-601 was infused alone Figure 7. Swim Plot after BPX-601 Administration* Cohort 4: Single-dose expansion in PSCA+ In patients who received Flu/Cy LD (cohort 5B): 6 • Figure 1. Inducible MyD88/CD40 (iMC) 2.5 x 10 cells/kg rimiducid pancreatic, gastric, Apheresis --All events of febrile neutropenia and neutropenia were Grade ≥3 and were not related to BPX-601/rimiducid; frequency 0.4 mg/kg and prostate cancer 1 (2) Cohort 3: and severity of the observed hematologic toxicity is generally consistent with Flu/Cy LD5,6 Figure 5. Peripheral Cytokine Profiles Over Time* MyD88 CD40 iMC 1.25 x 106 cells/kg 2 (1) Lymphodepletion TLRs 1, 2, 4–6 CD40 --The events of dysuria and hematuria were mostly Grade 1-2 (1 event of Grade 3 hematuria) and were related to Rimiducid PSCA+, (Cy ± Flu)* Cohort 0: BPX-601/rimiducid 3 (1) advanced 1.25 x 106 cells/kg IL-6 IP-10 pancreatic Routine safety and ef cacy --Patient 4 experienced an SAE of Grade 2 cytokine release syndrome (CRS) 1 day after rimiducid infusion; the patient 1 (2) TIR MyD88 evaluations up to 60 months Rim Cytoplasmic cancer Between FKBP12v36 Between Day 0 Day 7 was treated with IV tocilizumab (single infusion) and the event resolved the same day 1000 Rim 100000 TLRs 7, 8, 9 domain Days -42 Days −5 2 (3) FKBP12v36 and -8 and −3 --Patient 2 experienced an SAE of Grade 2 encephalopathy on the same day of rimiducid infusion; no concurrent CRS 3 (2) CD40 was observed, the patient was treated with IV dexamethasone, and the event resolved within 1 week Current status of Phase 1: enrollment ongoing in Cohort 5 100 10000 MyD88 1 (2) MyD88 *Cohorts 0, 3, 4, and 5A received Cy alone on Day −3 for LD; cohort 5B received Flu/Cy on Day −5 to −3 for LD. Table 2. Safety Summary 3 (5) Cy, cyclophosphamide; Flu, fludarabine; LD, lymphodepletion; PSCA, prostate stem cell antigen. 10 1000 AP1 NFκB IRF7 NFκB AP1 NFκB AP1 IRF7 Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B All Patients 4 (2)† Serum IL-6 (pg/ml) Main Inclusion Criteria Patients, n (%) n = 3 n = 3 n = 3 n = 4 n = 5 N = 18 Serum IP-10 (pg/ml) Proinflammatory cytokines, type I interferons, proliferation Any AE 3 (100) 3 (100) 3 (100) 4 (100) 5 (100) 18 (100) 1 (4) • Histologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma with disease progression after standard 1 100 Other immune functions Any SAE 2 (67) 1 (33) 0 3 (75) 4 (80) 10 (56) 0 10 20 30 40 50 0 10 20 30 40 50 or investigational therapy for non-resectable disease Grade 3 & 4 TRAEs 0 0 0 0 1 (20) 1 (<1) 2 (2) Time (Days) CD40, cluster of differentiation 40; FKBP, FK506-binding protein; MyD88, myeloid differentiation primary response 88; TIR, toll/interleukin-1 receptor; AEs in >15% of all patients, n (%) Time (Days) • Positive tumor expression of PSCA as determined by qPCR performed by a central laboratory 3 (1) TLR, toll-like receptor. Febrile neutropenia 0 0 0 2 (50) 4 (80) 6 (33) • Age ≥18 years Fatigue 2 (67) 1 (33) 0 2 (50) 0 5 (28) 4 (1) • GoCAR-T technology combines antigen-specific CAR-T cells with iMC in order to allow control of T cell survival even in the Performance status 0 or 1 with adequate organ function Neutropenia 0 0 0 1 (25) 4 (80) 5 (28) 1 • IL-2 IL-5 absence of antigen (Figure 2) Pyrexia 0 0 1 (33) 2 (50) 2 (40) 5 (28) Patient (# of prior systemic therapies) 5 (1) Dysuria 0 0 0 0 4 (80) 4 (22) BPX-601 is an autologous GoCAR-T product candidate engineered to contain a prostate stem cell antigen (PSCA)- Main Exclusion Criteria • Hematuria 0 0 0 0 4 (80) 4 (22) Rim 0 5 10 15 20 25 30 directed CAR (PSCA-CD3ζ) plus iMC • Islet cell neoplasms 100 1000 Rim Nausea 2 (67) 0 0 0 2 (40) 4 (22) Weeks • Investigational therapy within 4 weeks or chemotherapy or immunotherapy within 2 weeks prior to BPX-601 infusion Abdominal pain 1 (33) 1 (33) 0 0 1 (20) 3 (17) GoCAR-T: BPX-601 Overview ‡ Figure 2. • Active autoimmune disease requiring systemic immunosuppressive therapy Abdominal pain upper 0 1 (33) 1 (33) 1 (25) 0 3 (17) SD PD Pseudo PD (clinical exam) Death Cohort 3 Cohort 4 Cohort 5A Cohort 5B Anemia 0 0 0 1 (25) 2 (40) 3 (17) 10 100 TCR • Uncontrolled systemic infection Back pain 1 (33) 1 (33) 0 1 (25) 0 3 (17) *Right arrow cap indicates ongoing treatment-free interval; †Patient withdrew consent for further follow-up; ‡Patient 2 was not efficacy evaluable due to Rimiducid α complex β Blood bilirubin increased 0 0 0 1 (25) 2 (40) 3 (17) non-measurable disease at baseline. PD, progressive disease; pseudo, pseudoprogression; SD, stable disease. Statistical Analysis Hypotension 0 0 2 (67) 1 (25) 0 3 (17) 1 10 CD3 All patients who were infused with BPX-601 were included in this data set AE, adverse event; SAE, serious adverse event; TRAE, treatment-related adverse event. Serum IL-2 (pg/ml) Cell • Serum IL-5 (pg/ml) Controllable iMC ζ CAR ζ Autonomous • Adverse events (AEs) were summarized by system organ class and preferred term Functions Functions • Flu/Cy LD resulted in a mean reduction in absolute lymphocyte count of 93.8% (SD 5.9%; n = 5) compared with 25.3% 0.1 1 • Incidence of AEs and serious AEs (SAEs) were summarized overall and with respect to CTCAE grade and relationship to 0 10 20 30 40 50 0 10 20 30 40 50 CONCLUSIONS ANTIGEN-INDEPENDENT CD3ζ (SD 23.5%; n = 13) with Cy LD alone (Figure 4) ANTIGEN-DEPENDENT SURVIVAL study treatment Time (Days) Time (Days) IL-2 CYTOTOXICITY --Increased peripheral IL-7 and IL-15 was observed in patients who received Flu/Cy, but not Cy alone for LD • Administration of BPX-601 followed by single-dose rimiducid was well tolerated with no dose-limiting toxicities • Anti-tumor activity was analyzed according to RECIST v1.1 --Frequent AEs were generally consistent with those experienced by advanced cancer patients undergoing cytotoxic NF-ĸB NFATc • Rapid T cell expansion by Day 4 was observed in the majority of patients; limited peripheral expansion occurred when BPX-601 was infused without rimiducid chemotherapy or other cancer immunotherapies • Nine of 17 patients (53%) with a minimum of 28 days of follow-up samples had BPX-601 persistence for >21 days, --The majority of AEs related to BPX-601/rimiducid were mild to moderate in intensity and resolved with or without RESULTS including all 5 patients in cohort 5B Cohort 0 Cohort 3 Cohort 4 supportive care Cellular Proliferation 1.25 x 106 cells/kg (Cy) 1.25 x 106 cells/kg + Rim (Cy) 2.5 x 106 cells/kg + Rim (Cy) As of April 23, 2019, 18 patients have been treated across 4 BPX-601 dose levels, including one cohort that received cells • Analysis of the relationship between PSCA copy number and maximum CAR vector copy number showed a weak • Compared with a single dose of Cy alone, more intense lymphodepletion with Flu/Cy is associated with elevations of • 2 CAR, chimeric antigen receptor; iMC, inducible MyD88/CD40; PSCA, prostate stem cell antigen; TCR, T cell receptor. without subsequent rimiducid (Table 1) correlation (R = 0.1294; P=.1426) IL-7 and IL-15 and significantly increased BPX-601 expansion and prolonged persistence in patients treated with Cohort 5A Cohort 5B single-dose rimiducid Per FDA request, conditioning chemotherapy was originally limited to a single IV infusion of Cy only on Day −3 for • PSCA is a target of particular interest for therapeutic intervention as it is upregulated in many solid tumors, including • 5.0 x 106 cells/kg + Rim (Cy) 5.0 x 106 cells/kg + Rim (Flu/Cy) 13 patients (cohorts 0-5A); following a protocol amendment, 5 patients were treated with Flu/Cy on Days −5 to −3 prior to • Evidence of biological activity/stable disease has been observed in heavily pre-treated pancreatic cancer patients cancers of the pancreas2 Figure 4. BPX-601 Expansion and Persistence receiving 5.0 x 106 cells/kg on Day 0 (cohort 5B) • Evaluation of safety and efficacy of BPX-601 followed by repeat-dose rimiducid is planned • Additionally, expression of PSCA has been observed in normal prostate epithelium, urinary bladder, kidney, esophagus, 3 • All patients had advanced pancreatic cancer and had been treated with 1 or more prior systemic therapies ALC IL-7 IL-15 • Collection of pre- and on-treatment biopsies were added to the study in a recent protocol amendment; tissue analysis stomach, and placenta t Cy *Each line represents data for an individual patient in the indicated cohort. • PSCA copy number was measured at screening and ranged from 5,000 to over 969,000 2.0 25 80 Rim, rimiducid. results will be presented at a later date ou n ) ) • By combining the properties of PSCA-specificity and control of T cell survival, BPX-601 is optimized for antigen-dependent l Flu/Cy C m m l 20 and -independent T cell activation, proliferation and persistence, which potentially may enhance its efficacy in solid tumors e 1.5 60 g / ) l pg / p Of 13 efficacy-evaluable patients treated with BPX-601 and a single dose of rimiducid, 8 patients (62%) had stable disease ( • ( compared with traditional CAR-T cells Table 1. Patient Demographics and Clinical Characteristics μ 15 5 7 / ho cy t 1 3 including 3 patients with tumor shrinkage of 10% to 24% (Figure 6) p 0 1.0 - 40 L - I 1 6 † L m • Standard treatment in the second- and third-line settings for metastatic pancreatic cancer is associated with a median Cohort LD Regimen* BPX-601 Dose (x10 cells/kg) Rim (Y/N) Patient Age/Sex # Prior Systemic Therapies PSCA (copies) I REFERENCES x y 10 ( 4 L m progression free survival of 2-3 months u m e − r u N 1 50/F 1 5,000 t 0.5 20 • Since the previous data cutoff, tumor shrinkage ( 13%) has been seen in 1 patient in cohort 5B (patient 5) e u 5 l 1. Foster AE, et al. Mol Ther. 2017;25(9):2176–2188. Se r S o 0 Cy only 1.25 N 2 58/F 3 377,000 s 2. Abate-Daga D, et al. Hum Gene Ther. 2014;25(12):1003–1012. b 0.0 0 0 N 3 65/F 5 15,000 A Baseline Day 0 Baseline Day 0 Baseline Day 0 Figure 6. Evidence of Anti-Tumor Activity in BPX-601-Treated Patients 3. Bellicum data on file. OBJECTIVE Y 1 59/F 2 34,000 4. Taieb J, et al. Ann Oncol. 2017;28(7):1473–83. Rim 5. Fludarabine phosphate injection [prescribing information]. Princeton, NJ: Sandoz; 2010. 100000 Cohort 0 3 Cy only 1.25 Y 2 70/M 1 7,000 6. Cyclophosphamide injection [prescribing information]. Deerfield, IL: Baxter Healthcare Corporation; 2013. • To determine safety and tolerability, recommended dose for expansion, pharmacodynamics, and anti-tumor activity of 1.25 x 106 cells/kg (Cy) Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B All Patients Y 3 58/F 1 31,000 Best Response (RECIST v1.1) BPX-601 with or without rimiducid in patients with previously treated advanced solid tumors with high PSCA expression 10000 Cohort 3 n = 3 n = 3 n = 3 n = 2* n = 5 N = 16 T* Y 1 71/F 2 7,686 - 1.25 x 106 cells/kg + Rim (Cy) R A μ g gDNA) 1000 4 Cy only 2.5 Y 2 60/F 3 354,730 / Cohort 4 C s Progressive Disease (PD), n 2 1 1 1 2 7 o DISCLOSURES 6 e 2.5 x 10 cells/kg + Rim (Cy) i Y 3 65/M 2 8,243 G p 100 METHODS o Cohort 5A† CR Becerra has received honoraria from Taiho Pharmaceutical; has consulted for SOBI, Ipsen, Takeda, Bayer, Heron Therapeutics, and Agenus; Y 1 61/M 2 14,238 C • ( 5.0 x 106 cells/kg + Rim (Cy) Stable Disease (SD), n 1 2 2 1 3 9 has participated in speakers’ bureaus for Taiho Pharmaceutical, Bristol-Myers Squibb, Merck Serono, and Celgene Study Design Y 2 64/M 1 19,533 LOQ GA Manji has received research funding from Plexxikon and ASCO; has been a consultant/advisory board member for Ardelyx 5A Cy only 5.0 0 10 20 30 40 50 60 90 180 Cohort 5B • • BP-012 is a 2-phase, first-in-human study to assess the safety, biologic, and clinical activity of BPX-601 plus rimiducid in N‡ 3 59/M 5 969,094 Time (Days) 5.0 x 106 cells/kg + Rim (Flu/Cy) Partial Response (PR), n 0 0 0 0 0 0 • DW Kim has no disclosures to report O Gardner, A Malankar, J Shaw, D Blass, X Yi, A Foster, and P Woodard are employees of Bellicum Pharmaceuticals and may own company stock/options select PSCA-positive solid tumors (Figure 3) Y 4 55/M 2 52,979 • Peak VCN Comparisons • Phase 1 is an ongoing 3+3 cell dose escalation designed to identify the recommended BPX-601 dose given in combination Y 1 56/M 4 201,277 Complete Response (CR), n 0 0 0 0 0 0 with rimiducid for use in Phase 2 dose expansion Patient Subsets Difference in Peak VCN P value Y 2 77/M 2 18,980 • After apheresis and LD with cyclophosphamide (Cy; 1 g/m²) alone on Day −3 (cohorts 0, 3, 4, and 5A) or fludarabine + Cy All Flu/Cy pts (n = 5) vs all Cy alone pts (n = 13) All Flu/Cy pts had 4.9-fold higher peak VCN P=.0028 Overall Response Rate (CR + PR), n (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) ACKNOWLEDGMENTS (Flu/Cy; 30 mg/m2 and 500 mg/m², respectively) on Days −5 to −3 (cohort 5B), patients were treated with escalating doses 5B Flu/Cy 5.0 Y 3 72/M 1 21,099 Flu/Cy + Rim pts (n = 5) vs Cy alone + Rim pts (n = 10) Flu/Cy + Rim pts had 4-fold higher peak VCN P=.0080 of BPX-601 (single intravenous [IV] infusion) on Day 0 followed by a fixed dose of rimiducid (0.4 mg/kg, single IV infusion) Y 4 58/M 1 149,110 5.0 x 10⁶ cells/kg and Flu/Cy LD pts (n = 5) vs 5.0 x 10⁶ cells/kg and Flu/Cy LD pts had 6.8-fold • The authors would like to acknowledge all patients and their families and caregivers for participating in this clinical trial, along with the investigators P=.0159 Disease Control Rate 5.0 x 10⁶ cells/kg and Cy alone LD pts (n = 4) higher peak VCN 1 (33) 2 (67) 2 (67) 1 (50) 3 (60) 9 (56) • Medical writing support was provided by Amanda Martin, PhD, of Medical Expressions (Chicago, IL), funded by Bellicum Pharmaceuticals on Day 7 Y 5 68/F 1 54,877 (CR + PR + SD), n (%) To evaluate the safety of T cell therapy alone, an initial cohort received BPX-601 on Day 0 and did not receive subsequent • *Cy (1 g/m2) by IV infusion on Day −3, Flu/Cy (30 mg/m2 and 500 mg/m², respectively) by IV infusion on Days −5 to −3; †PSCA (copies per 10⁶ copies hACTB) was rimiducid (cohort 0) measured at screening; ‡Patient was scheduled to receive Rim, but infusion was delayed then withdrawn due to an AE associated with worsening disease. Patient *Data points represent the mean log VCN for each cohort and the dotted red line represents rimiducid administration at Day 7; †Patient 3 in cohort 5A did not have subsequently died due to disease progression. data for time points beyond Day 4 and thus is not included in the summary of cell persistence. *2 patients in cohort 5A (2 and 3) were not efficacy evaluable due to non-measurable disease at baseline and death due to disease under study prior to first • Patients treated with BPX-601 with or without rimiducid were followed for routine safety, blood biomarkers, and efficacy AE, adverse event; Cy, cyclophosphamide; Flu, fludarabine; hACTB, human beta-actin; LD, lymphodepletion; PSCA, prostate stem cell antigen; Rim, rimiducid. ALC, absolute lymphocyte count; Cy, cyclophosphamide; Flu, fludarabine; LOQ, limit of quantitation; pts, patients; Rim, rimiducid; VCN, vector copy number. post-baseline efficacy measurement, respectively. Copies of this poster obtained through Quick Response (QR) Code are for personal use only evaluations as specified by the study protocol and may not be reproduced without permission from ASCO® and the author of this poster. Presented at the Annual Meeting 2019, American Society of Clinical Oncology – May 31 - June 4, 2019, Chicago, IL
Ligand-Inducible, Prostate Stem Cell Antigen (PSCA)-Directed GoCAR-T® Cells in Advanced Solid Tumors: Abstract #2536 Preliminary Results With Cyclophosphamide (Cy) ± Fludarabine (Flu) Lymphodepletion (LD) Carlos R. Becerra,1 Gulam Manji,2 Dae Won Kim,3 Olivia Gardner,4 Aditya Malankar,4 Joanne Shaw,4 Devin Blass,4 Xiaohui Yi,4 Aaron Foster,4 Paul Woodard4 1Baylor University Medical Center, Dallas, TX; 2Columbia University, New York, NY; 3Moffitt Cancer Center, Tampa, FL;4 Bellicum Pharmaceuticals, Inc., Houston, TX. • All BPX-601-treated patients reported at least 1 adverse event (AE); the most common AEs (in >20% of all patients) • As shown in Figure 5, following single-dose rimiducid on Day 7: • With 9.1 weeks median duration of follow-up (range: 2.9–30.3 weeks), the median time to follow-on cancer therapy in BP-012 (NCT02744287) Study Design Figure 3. regardless of causality, LD regimen, or BPX-601 dose were febrile neutropenia (33%), fatigue (28%), neutropenia (28%), patients who received subsequent therapy was 16.6 weeks (range: 5.6–30.3 weeks; Figure 7) --Rimiducid-dependent elevations in IL-2, IL-5, IL-6, and IP-10 were observed in most patients, particularly those in pyrexia (28%), dysuria (22%), hematuria (22%), and nausea (22%) (Table 2) 6 BACKGROUND Single infusion BPX-601 cell dose cohort 5B, and correlated with cell expansion • At the highest cell dose (5.0 x 10 cells/kg) after Flu/Cy LD followed by a single rimiducid dose at Day 7: escalation (3+3) based on safety • As of the data cut off, no BPX-601 dose limiting toxicities were observed --2 patients with at least 9.1 weeks of follow-up had a time to next treatment of >22 weeks which was ongoing at the time • Inducible MyD88/CD40 (iMC) is a novel co-activation switch comprised of two synergistic signaling domains regulated by --Similar rimiducid-dependent increases in IL-8, G-CSF, MCP-1, MIP-1α, and MIP-1β were also observed (data not shown) 1 Cohort 5A: • Nine patients (50%) reported treatment-related AEs (TRAEs); dysuria (n = 4), hematuria (n = 4), pyrexia (n = 3), of the data cutoff the synthetic small-molecule ligand, rimiducid (Figure 1) 6 5.0 x 10 cells/kg and hypotension (n = 2) were reported by ≥2 patients --Increased serum IP-10 was indicative of prior IFN-γ production and, together with increased serum TNF-α, supports • iMC contains a rimiducid-binding domain (two FK506-binding proteins) coupled with the signaling components from after Cy LD --1 patient who had previously received 2 lines of systemic therapy (patient 2) had stable disease that was ongoing at All TRAEs were mild/moderate except for Grade 3 hematuria and Grade 3 groin pain reported by 1 patient; T cell activation in response to activation of iMC by rimiducid MyD88 and CD40, which play critical roles in initiation and maintenance of an innate and adaptive immune response1 Cohort 5B: • 6 months 5.0 x 106 cells/kg no Grade 4 TRAEs were reported --Increased BPX-601 dose was associated with overall increased serum cytokine and chemokine levels • Transcription factor activation via the MyD88 and CD40 signaling domains leads to upregulation of proinflammatory after Flu/Cy LD Cohorts Phase 2: 1 • Ten patients (56%) reported serious AEs (SAEs); febrile neutropenia was the only SAE reported by >1 patient (n = 5) cytokines and type I interferons, which promote proliferation, activation, and survival of immune cells, including T cells 3, 4, 5: multi-arm dose • Limited peripheral cytokine changes were observed when BPX-601 was infused alone Figure 7. Swim Plot after BPX-601 Administration* Cohort 4: Single-dose expansion in PSCA+ In patients who received Flu/Cy LD (cohort 5B): 6 • Figure 1. Inducible MyD88/CD40 (iMC) 2.5 x 10 cells/kg rimiducid pancreatic, gastric, Apheresis --All events of febrile neutropenia and neutropenia were Grade ≥3 and were not related to BPX-601/rimiducid; frequency 0.4 mg/kg and prostate cancer 1 (2) Cohort 3: and severity of the observed hematologic toxicity is generally consistent with Flu/Cy LD5,6 Figure 5. Peripheral Cytokine Profiles Over Time MyD88 CD40 iMC 1.25 x 106 cells/kg 2 (1) Lymphodepletion TLRs 1, 2, 4�6 CD40 --The events of dysuria and hematuria were mostly Grade 1-2 (1 event of Grade 3 hematuria) and were related to Rimiducid PSCA+, (Cy ± Flu)* Cohort 0: BPX-601/rimiducid 3 (1) advanced 1.25 x 106 cells/kg IL-6 IP-10 pancreatic Routine safety and ef cacy --Patient 4 experienced an SAE of Grade 2 cytokine release syndrome (CRS) 1 day after rimiducid infusion; the patient 1 (2) TIR MyD88 evaluations up to 60 months Rim Cytoplasmic cancer Between FKBP12v36 Between Day 0 Day 7 was treated with IV tocilizumab (single infusion) and the event resolved the same day 1000 Rim 100000 TLRs 7, 8, 9 domain Days -42 Days −5 2 (3) FKBP12v36 and -8 and −3 --Patient 2 experienced an SAE of Grade 2 encephalopathy on the same day of rimiducid infusion; no concurrent CRS 3 (2) CD40 was observed, the patient was treated with IV dexamethasone, and the event resolved within 1 week Current status of Phase 1: enrollment ongoing in Cohort 5 100 10000 MyD88 1 (2) MyD88 * Cohorts 0, 3, 4, and 5A received Cy alone on Day −3 for LD; cohort 5B received Flu/Cy on Day −5 to −3 for LD. Table 2. Safety Summary 2 (5) Cy, cyclophosphamide; Flu, fludarabine; LD, lymphodepletion; PSCA, prostate stem cell antigen. 10 1000 AP1 NFκB IRF7 NFκB AP1 NFκB AP1 IRF7 Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B All Patients 3 (2)† Serum IL-6 (pg/ml) Main Inclusion Criteria Patients, n (%) n = 3 n = 3 n = 3 n = 4 n = 5 N = 18 Serum IP-10 (pg/ml) Proinflammatory cytokines, type I interferons, proliferation Any AE 3 (100) 3 (100) 3 (100) 4 (100) 5 (100) 18 (100) 1 (4) • Histologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma with disease progression after standard 1 100 Other immune functions Any SAE 2 (67) 1 (33) 0 3 (75) 4 (80) 10 (56) 0 10 20 30 40 50 0 10 20 30 40 50 or investigational therapy for non-resectable disease Grade 3 & 4 TRAEs 0 0 0 0 1 (20) 1 (<1) 2 (2) Time (Days) CD40, cluster of differentiation 40; FKBP, FK506-binding protein; MyD88, myeloid differentiation primary response 88; TIR, toll/interleukin-1 receptor; AEs in >15% of all patients, n (%) Time (Days) • Positive tumor expression of PSCA as determined by qPCR performed by a central laboratory 3 (1) TLR, toll-like receptor. Febrile neutropenia 0 0 0 2 (50) 4 (80) 6 (33) • Age ≥18 years Fatigue 2 (67) 1 (33) 0 2 (50) 0 5 (28) 4 (1) • GoCAR-T technology combines antigen-specific CAR-T cells with iMC in order to allow control of T cell survival even in the Performance status 0 or 1 with adequate organ function Neutropenia 0 0 0 1 (25) 4 (80) 5 (28) 1 • IL-2 IL-5 absence of antigen (Figure 2) Pyrexia 0 0 1 (33) 2 (50) 2 (40) 5 (28) Patient (# of prior systemic therapies) 5 (1) Dysuria 0 0 0 0 4 (80) 4 (22) BPX-601 is an autologous GoCAR-T product candidate engineered to contain a prostate stem cell antigen (PSCA)- Main Exclusion Criteria • Hematuria 0 0 0 0 4 (80) 4 (22) Rim 0 5 10 15 20 25 30 directed CAR (PSCA-CD3ζ) plus iMC • Islet cell neoplasms 100 1000 Rim Nausea 2 (67) 0 0 0 2 (40) 4 (22) Weeks • Investigational therapy within 4 weeks or chemotherapy or immunotherapy within 2 weeks prior to BPX-601 infusion Abdominal pain 1 (33) 1 (33) 0 0 1 (20) 3 (17) GoCAR-T: BPX-601 Overview ‡ Figure 2. • Active autoimmune disease requiring systemic immunosuppressive therapy Abdominal pain upper 0 1 (33) 1 (33) 1 (25) 0 3 (17) SD PD Pseudo PD (clinical exam) Death Cohort 3 Cohort 4 Cohort 5A Cohort 5B Anemia 0 0 0 1 (25) 2 (40) 3 (17) 10 100 TCR • Uncontrolled systemic infection Back pain 1 (33) 1 (33) 0 1 (25) 0 3 (17) * Right arrow cap indicates ongoing treatment-free interval; † Patient withdrew consent for further follow-up; ‡ Patient 2 was not efficacy evaluable due to Rimiducid α complex β Blood bilirubin increased 0 0 0 1 (25) 2 (40) 3 (17) non-measurable disease at baseline. PD, progressive disease; pseudo, pseudoprogression; SD, stable disease. Statistical Analysis Hypotension 0 0 2 (67) 1 (25) 0 3 (17) 1 10 CD3 All patients who were infused with BPX-601 were included in this data set AE, adverse event; SAE, serious adverse event; TRAE, treatment-related adverse event. Serum IL-2 (pg/ml) Cell • Serum IL-5 (pg/ml) Controllable iMC ζ CAR ζ Autonomous • Adverse events (AEs) were summarized by system organ class and preferred term Functions Functions • Flu/Cy LD resulted in a mean reduction in absolute lymphocyte count of 93.8% (SD 5.9%; n = 5) compared with 25.3% 0.1 1 • Incidence of AEs and serious AEs were summarized overall and with respect to CTCAE grade and relationship to 0 10 20 30 40 50 0 10 20 30 40 50 CONCLUSIONS ANTIGEN-INDEPENDENT CD3ζ (SD 23.5%; n = 13) with Cy LD alone (Figure 4) ANTIGEN-DEPENDENT SURVIVAL study treatment Time (Days) Time (Days) IL-2 CYTOTOXICITY --Increased peripheral IL-7 and IL-15 was observed in patients who received Flu/Cy, but not Cy alone for LD • Administration of BPX-601 followed by single-dose rimiducid was well tolerated with no dose-limiting toxicities • Anti-tumor activity was analyzed according to RECIST v1.1 --Frequent AEs were generally consistent with those experienced by advanced cancer patients undergoing cytotoxic �F-ĸ� �FATc • Rapid T cell expansion by Day 4 was observed in the majority of patients; limited peripheral expansion occurred when BPX-601 was infused without rimiducid chemotherapy or other cancer immunotherapies RESULTS • Nine of 17 patients (53%) with a minimum of 28 days of follow-up samples had BPX-601 persistence for >21 days, --The majority of AEs related to BPX-601/rimiducid were mild to moderate in intensity and resolved with supportive care including all 5 patients in cohort 5B Cohort 0 Cohort 3 Cohort 4 • Compared with a single dose of Cy alone, more intense lymphodepletion with Flu/Cy is associated with elevations of Cellular Proliferation 1.25 x 106 cells/kg (Cy) 1.25 x 106 cells/kg + Rim (Cy) 2.5 x 106 cells/kg + Rim (Cy) As of April 23, 2019, 18 patients have been treated across 4 BPX-601 dose levels, including one cohort that received cells • Analysis of the relationship between PSCA copy number and maximum CAR vector copy number showed a weak IL-7 and IL-15 and significantly increased BPX-601 expansion and prolonged persistance in patients treated with • 2 CAR, chimeric antigen receptor; iMC, inducible MyD88/CD40; PSCA, prostate stem cell antigen; TCR, T cell receptor. without subsequent rimiducid (Table 1) correlation (R = 0.1294; P=.1426) single-dose rimiducid Cohort 5A Cohort 5B Per FDA request, conditioning chemotherapy was originally limited to a single IV infusion of Cy only on Day −3 for • Evidence of biological activity/stable disease has been observed in heavily pre-treated pancreatic cancer patients • PSCA is a target of particular interest for therapeutic intervention as it is upregulated in many solid tumors, including • 5.0 x 106 cells/kg + Rim (Cy) 5.0 x 106 cells/kg + Rim (Flu/Cy) 13 patients (cohorts 0-5A); following a protocol amendment, 5 patients were treated with Flu/Cy on Days −5 to −3 prior to cancers of the pancreas2 Figure 4. BPX-601 Expansion and Persistence* • Evaluation of safety and efficacy of BPX-601 followed by repeat-dose rimiducid is planned receiving 5.0 x 106 cells/kg on Day 0 (cohort 5B) • Additionally, expression of PSCA has been observed in normal prostate epithelium, urinary bladder, kidney, esophagus, • A repeat-dose rimiducid infusion schedule and collection of pre- and on-treatment biopsies were added to the study in a 3 • All patients had advanced pancreatic cancer and had been treated with 1 or more prior systemic therapies ALC IL-7 IL-15 recent protocol amendment; safety/activity data and tissue analysis results will be presented at a later date stomach, and placenta Cy Each line represents data for an individual patient in the indicated cohort. • PSCA copy number was measured at screening and ranged from 5,000 to over 969,000 2.0 25 80 Rim, rimiducid. • By combining the properties of PSCA-specificity and control of T cell survival, BPX-601 is optimized for antigen-dependent ou nt Flu/Cy 20 and -independent T cell activation, proliferation and persistence, which may potentially enhance its efficacy in solid tumors 1.5 60 l) pg /ml) • Of 13 efficacy-evaluable patients treated with BPX-601 and a single dose of rimiducid, 8 patients (62%) had stable disease compared with traditional CAR-T cells Table 1. Patient Demographics and Clinical Characteristics μ 15 / ho cy te C REFERENCES 3 1.0 40 including 3 patients with tumor shrinkage of 10% to 24% (Figure 6) • Standard treatment in the second- and third-line settings for metastatic pancreatic cancer is associated with a median Cohort LD Regimen* BPX-601 Dose (x106 cells/kg) Rim (Y/N) Patient Age/Sex # Prior Systemic Therapies PSCA (copies)† 10 x 10 progression free survival of 2-3 months4 ( 1. Foster AE, et al. Mol Ther. 2017;25(9):2176–2188. N 1 50/F 1 5,000 0.5 20 • Since the previous data cutoff, tumor shrinkage (−13%) has been seen in 1 patient in cohort 5B (patient 5) 5 2. Abate-Daga D, et al. Hum Gene Ther. 2014;25(12):1003–1012. Se rum IL-7 (pg/ml) Serum IL-15 ( 0 Cy only 1.25 N 2 58/F 3 377,000 3. Bellicum data on file. 0.0 0 0 N 3 65/F 5 15,000 Absolute Lymp Baseline Day 0 Baseline Day 0 Baseline Day 0 Figure 6. Evidence of Anti-Tumor Activity in BPX-601-Treated Patients 4. Taieb J, et al. Ann Oncol. 2017;28(7):1473–83. 5. Fludarabine phosphate injection [prescribing information]. Princeton, NJ: Sandoz; 2010. OBJECTIVE Y 1 59/F 2 34,000 Rim 6. Cyclophosphamide injection [prescribing information]. Deerfield, IL: Baxter Healthcare Corporation; 2013. 3 Cy only 1.25 Y 2 70/M 1 7,000 100000 Cohort 0 • To determine safety and tolerability, recommended dose for expansion, pharmacodynamics, and anti-tumor activity of 1.25 x 106 cells/kg (Cy) Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B All Patients Y 3 58/F 1 31,000 Best Response (RECIST v1.1) BPX-601 with or without rimiducid in patients with previously treated advanced solid tumors with high PSCA expression 10000 Cohort 3 n = 3 n = 3 n = 3 n = 2* n = 5 N = 16 Y 1 71/F 2 7,686 1.25 x 106 cells/kg + Rim (Cy) DISCLOSURES 4 Cy only 2.5 Y 60/F 4 8,243 μ g gDNA) 1000 2 Cohort 4 Progressive Disease (PD), n 2 1 1 1 2 7 2.5 x 106 cells/kg + Rim (Cy) Y 3 65/M 2 354,730 GoCAR-T • CR Becerra has received honoraria from Taiho Pharmaceutical; has consulted for SOBI, Ipsen, Takeda, Bayer, Heron Therapeutics, and Agenus; METHODS 100 † has participated in speakers’ bureaus for Taiho Pharmaceutical, Bristol-Myers Squibb, Merck Serono, and Celgene Y 1 61/M 3 14,238 Cohort 5A (Copies/ 5.0 x 106 cells/kg + Rim (Cy) Stable Disease (SD), n 1 2 2 1 3 9 • GA Manji has received research funding from Plexxikon and ASCO; has been a consultant/advisory board member for Ardelyx Study Design Y 2 64/M 1 19,533 LOQ • DW Kim has no disclosures to report 5A Cy only 5.0 0 10 20 30 40 50 60 90 180 Cohort 5B • BP-012 is a two-phase, first-in-human study to assess the safety, biologic, and clinical activity of BPX-601 plus rimiducid in N‡ 3 59/M 5 969,094 Time (Days) 5.0 x 106 cells/kg + Rim (Flu/Cy) Partial Response (PR), n 0 0 0 0 0 0 • O Gardner, A Malankar, J Shaw, D Blass, X Yi, A Foster, and P Woodard are employees of Bellicum Pharmaceuticals and may own company stock/options select PSCA-positive solid tumors (Figure 3) Y 4 55/M 2 52,979 Peak VCN Comparisons • Phase 1 is an ongoing 3+3 cell dose escalation designed to identify the recommended BPX-601 dose given in combination Y 1 56/M 4 201,277 Complete Response (CR), n 0 0 0 0 0 0 with rimiducid for use in Phase 2 dose expansion Patient Subsets Difference in Peak VCN P value Y 2 77/M 2 18,980 ACKNOWLEDGMENTS • After apheresis and LD with cyclophosphamide (Cy; 1 g/m²) alone on Day −3 (cohorts 0, 3, 4, and 5A) or fludarabine + Cy All Flu/Cy pts (n = 5) vs all Cy alone pts (n = 13) All Flu/Cy pts had 4.9-fold higher peak VCN P=.0028 Overall Response Rate (CR + PR), n (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) (Flu/Cy; 30 mg/m2 and 500 mg/m², respectively) on Days −5 to −3 (cohort 5B), patients were treated with escalating doses 5B Flu/Cy 5.0 Y 3 72/M 1 21,099 Flu/Cy + Rim pts (n = 5) vs Cy alone + Rim pts (n = 10) Flu/Cy + Rim pts had 4-fold higher peak VCN P=.0080 • The authors would like to acknowledge all patients and their families and caregivers for participating in this clinical trial, along with the investigators of BPX-601 (single intravenous [IV] infusion) on Day 0 followed by a fixed dose of rimiducid (0.4 mg/kg, single IV infusion) Y 4 58/M 1 149,110 5.0 x 10⁶ cells/kg and Flu/Cy LD pts (n = 5) vs 5.0 x 10⁶ cells/kg and Flu/Cy LD pts had 6.8-fold P=.0159 Disease Control Rate 1 (33) 2 (67) 2 (67) 1 (50) 3 (60) 9 (56) • Medical writing support was provided by Amanda Martin, PhD, of Medical Expressions (Chicago, IL), funded by Bellicum Pharmaceuticals on Day 7 Y 5 68/F 1 54,877 5.0 x 10⁶ cells/kg and Cy alone LD pts (n = 4) higher peak VCN (CR + PR + SD), n (%) To evaluate the safety of T cell therapy alone, an initial cohort received BPX-601 on Day 0 and did not receive subsequent • * Cy (1 g/m2) by IV infusion on Day −3, Flu/Cy (30 mg/m2 and 500 mg/m², respectively) by IV infusion on Days −5 to −3; † PSCA (copies per 10⁶ copies hACTB) was rimiducid (cohort 0) measured at screening; ‡ Patient was scheduled to receive Rim, but infusion was delayed then withdrawn due to an AE associated with worsening disease. Patient * Data points represent the mean log VCN for each cohort and the dotted red line represents rimiducid administration at Day 7; † Patient 3 in cohort 5A did not have subsequently died due to disease progression. data for time points beyond Day 4 and thus is not included in the summary of cell persistence. * 2 patients in cohort 5A (2 and 3) were not efficacy evaluable due to non-measurable disease at baseline and death due to disease under study prior to first • Patients treated with BPX-601 with or without rimiducid were followed for routine safety, blood biomarkers, and efficacy AE, adverse event; Cy, cyclophosphamide; Flu, fludarabine; hACTB, human beta-actin; LD, lymphodepletion; PSCA, prostate stem cell antigen; Rim, rimiducid. ALC, absolute lymphocyte count; Cy, cyclophosphamide; Flu, fludarabine; LOQ, limit of quantitation; pts, patients; Rim, rimiducid; VCN, vector copy number. post-baseline efficacy measurement, respectively. Copies of this poster obtained through Quick Response (QR) Code are for personal use only evaluations as specified by the study protocol and may not be reproduced without permission from ASCO® and the author of this poster. Presented at the Annual Meeting 2019, American Society of Clinical Oncology – May 31 - June 4, 2019, Chicago, IL