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): March 12, 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)) |
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.
We are furnishing this Current Report on Form 8-K in connection with the disclosure of information, in the form of a slide presentation, to be given at meetings with institutional investors or analysts. The slide presentation is attached hereto as Exhibit 99.1.
The information contained in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1, 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 Exhibit 99.1, 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 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit Number | Description | |
99.1 | ||
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: March 13, 2019 | By: | /s/ Richard A. Fair | ||||
Richard A. Fair | ||||||
President and Chief Executive Officer | ||||||
(Principal Executive Officer) | ||||||
Investor Presentation Striving to deliver cures through controllable cell therapy March 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. 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, gastric and prostate cancers ▪ Late interim results presented at ASH in Dec. 2018 trend ▪ toward meeting primary endpoint Initial safety data on 12 pancreatic patients presented at ESMO- ▪ IO in Dec. 2018 indicate attractive safety profile and early clinical Expect topline data in 1H 2019; MAA filings in 2H 2019 activity ▪ European HQ and leadership team in place for ▪ Trial amendments to lymphodepletion regimen and activation commercialization prep molecule administration to 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 of $98.0MM as of December 31, 2018; 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 Organ 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 Enables Control After Infusion Provides physicians 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 eafety more potent approaches ▪ iMC provides control over timing and frequency of co- activation ▪ CaspaCIDe rapidly eliminates a majority of CAR-T cells to manage acute toxicities 9
BPX-601 GoCAR-T Targeting Prostate Stem Cell Antigen Product Summary Unmet Need ▪ Attractive first-in-class solid tumor CAR-T opportunity High unmet need in solid tumors expressing Prostate Stem Cell Antigen (PSCA) ▪ First-in-human experience with iMC ▪ Incidence Annual % Expressing Initial Phase 1 results presented in Dec 2018 demonstrate: (US) Deaths (US) PSCA - Safety Pancreatic 55k 44k ~60% - iMC-driven T cell activation - Biologic activity Prostate 165k 29k 75-90% ▪ 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 Cohort 0 Cohort 3 Cohort 4 Cohort 5a Cohort 5b Next Cohort (Lead-in) 2L Pancreatic 2L Pancreatic Patient Population 3L+ Pancreatic 2L Gastric 2L Gastric HR-Refractory Prostate HR-Refractory Prostate BPX-601 Dose 1.25 1.25 2.5 5.0 5.0 x106 cells/kg @ Day 0 Rimiducid Dose Scheduled Repeat None Single Dose Single Dose Single Dose mg/kg @ Day 7 Dosing Cytoxan 0.5g/m2 Cytoxan 0.5g/m2 Fludarabine Fludarabine 30mg/m2 Cytoxan 1g/m2 Cytoxan 1g/m2 30mg/m2 Conditioning @ Days @ Day -3 @ Day -3 @ Days -5, -4, -3 -5, -4, -3 Status Enrolled Active Pending ClinicalTrials.gov Identifier: NCT02744287 11
BPX-601: No Dose Limiting Toxicities Observed Data presented at ESMO Immuno-Oncology Congress 2018 – clinical cut-off October 29, 2018 Most common AEs reported by > 1 patient Total (N=12) Any Event, n (%) 12 (100) ▪ Fatigue 4 (33) No dose limiting toxicities were observed Abdominal pain upper 3 (25) ▪ Pyrexia was the only Hypotension 3 (25) treatment-related AE reported by >1 patient (n=2) Abdominal pain 2 (17) - Grade 1–2 on Day 0 Back pain 2 (17) following BPX-601 infusion Diarrhea 2 (17) - Both events resolved within 24–36 hours with supportive Flatulence 2 (17) care Nausea 2 (17) Pyrexia 2 (17) AE, adverse event 12
BPX-601: iMC-Driven T Cell Expansion & Persistence Cohort 0 Cohort 3 Cohort 4 Cohort 5 1.25x106/kg 1.25x106/kg + Rim 2.5x106/kg + Rim 5x106/kg + Rim CAR-T CAR-T CAR-T CAR-T ▪ Limited evidence of LD with 1 0 0 0 0 2 5 0 0 0 Rim 1 0 0 0 0 Rim 1 0 0 0 0 Rim 2 0 0 0 0 CTX-only regimen (79% ± 25% 8 0 0 0 PSCA = 1 0 0 0 0 PSCA = 8 0 0 0 PSCA = 8 0 0 0 PSCA = 6 0 0 0 5,000 copies 8 0 0 0 34,000 6 0 0 0 7,686 6 0 0 0 14,238 of cells remained) 6 0 0 0 4 0 0 0 4 0 0 0 4 0 0 0 copies 4 0 0 0 copies copies 2 0 0 0 2 0 0 0 * 2 0 0 0 * * * * * * * 2 0 0 0 ▪ 0 0 0 0 Rapid cell expansion by Day 4, -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 but no persistence without Rim 1 0 0 0 0 2 5 0 0 0 1 0 0 0 0 1 0 0 0 0 2 0 0 0 0 PSCA = 8 0 0 0 PSCA = 1 0 0 0 0 PSCA = 8 0 0 0 PSCA = 8 0 0 0 6 0 0 0 377,000 8 0 0 0 7,000 copies 6 0 0 0 8,243 6 0 0 0 19,533 ▪ 6 0 0 0 With single-dose Rim: 4 0 0 0 4 0 0 0 copies 4 0 0 0 copies copies 4 0 0 0 2 0 0 0 2 0 0 0 * * * * 2 0 0 0 * * * * * * * 2 0 0 0 Copies/µggDNA Cell expansion of 3 to 20-fold 0 0 0 0 - -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 within 7 days in 4 patients T im e (D a y s ) 1 0 0 0 0 2 5 0 0 0 1 0 0 0 0 PSCA = 2 0 0 0 0 PSCA = PSCA = 8 0 0 0 1 0 0 0 0 8 0 0 0 - Cell persistence of 31,000 6 0 0 0 15,000 copies 8 0 0 0 6 0 0 0 354,730 6 0 0 0 >3 weeks in 3 patients 4 0 0 0 copies 4 0 0 0 copies 4 0 0 0 2 0 0 0 * * 2 0 0 0 2 0 0 0 0 0 0 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 -7 0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5 T im e (D a y s ) T im e (D a y s ) T im e (D a y s ) Time (Days) * Vector copy number < limit of quantification. CTX, cyclophosphamide; LD, lymphodepletion; PSCA, prostate stem cell antigen; Rim, rimiducid. 13
BPX-601: Evidence of Anti-Tumor Activity Best Response (RECIST) Cohort Two patients with SD had CR PR SD PD tumor shrinkage >20% 0 0 0 1 2 3 0 0 2 1 Disease control without new therapies: 16 and 4 0 0 2 1 >18 weeks in 1 and 3 patients, respectively Patient 3A | 2 prior therapies; PSCA = 34,000 copies Baseline Month 1 Month 2 Month 4 ▪ Lesion longest diameter: 70 mm ▪ Lesion longest diameter: 57 mm ▪ Lesion longest diameter: 49 mm ▪ Lesion longest diameter: 40 mm ▪ CA19-9: 294 ▪ CA19-9: 152.6 ▪ CA19-9: 207.2 ▪ CA19-9: 641.4 ▪ Overall response: SD (−15%) ▪ Possible new lesion ▪ New lesion confirmed ▪ Overall response: SD (−25%) ▪ Overall response: PD CA19-9, cancer antigen 19-9; CR, complete response; PD, progressive disease; PR, partial response; PSCA, prostate stem cell antigen; SD, stable disease. 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; 2Lui et al., Cancer Res 2004; 3Gravolos 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 Hegde, 2017 Feng, 2017 Ahmed, 2017 Construct 4D5-28-BB-z FRP5-28-z FRP5-28-z Her2-BB-z FRP5-28-z Indication(s) Metastatic colon Sarcomas Sarcomas CCA and PCa GBM Patient number 1 19 6 11 17 HER2 expression ≥2+ (IHC) ≥1+ (IHC) ≥1+ (IHC) >50% positive ≥1+ (IHC) CAR-T dose 1010 104 - 108 108 106 106 - 108 CAR-T expansion NE Negligible >10,000 copies >1,000 copies Negligible Toxicity Lung reactivity No DLTs Mild AEs Mild AEs Mild AEs Outcome Grade 5 toxicity 1 PR, 3 SD,13 PD 2 CR, 2 SD 1 PR, 5 SD 1 PR, 7 PD Total Responses 2 CR, 3 PR, 5/54 (9.3% 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 HCST 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
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 20
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 ▪ 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; 21 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 22
Rivo-cel: High Rates of Disease-Free and Overall Survival Interim survival results With median 20.3 months N= 166, Events = 9, Overall Survival 94.4% (0.5 – 47.4 months): (95% CI 90.8-98%) ▪ Relapse-free survival 82.9% in malignant patients ▪ Disease-free survival 95.2% in non- malignant patients 23
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 1 treatment were eligible to receive ▪ rimiducid ≥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 2 ▪ Four patients in PR or not evaluable iC9 , 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 24
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 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
Execution of Key Objectives 28
Bellicum Leadership Team Rick Fair William Grossman Atabak Mokari President & CEO Chief Medical Officer Chief Financial Officer Gregory Naeve Aaron Foster Alan Smith Chief Business Officer Senior Vice President Exec. Vice President Head of Research Tech Operations Shane Ward Thierry Darcis General Counsel & General Manager, Europe Corporate Secretary 29
Substantial Progress Achieved in 2018 Delivered on commitments and strengthened the organization 2018 To-Do List Complete enrollment in cell dose escalation portion of BP-012 Phase 1/2 study BPX-601 Present initial clinical data at medical meeting Complete enrollment & present IA on BP-004 and C/CP-004 comparator studies Initiate Phase 2/3 study in adult & adolescent AML & MDS Rivo-cel Confirm pediatric approval pathway in US Initiate commercial launch preparation in Europe BPX-701 Present initial clinical data at medical meeting PIPELINE Complete dual-switch constructs for two new GoCAR-T candidates Complete build-out of Houston cell & viral vector manufacturing facility ORG Establish site in San Francisco Bay Area and European HQ Strengthen the leadership team 30
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 (Cy/flu regimen) (repeat rimiducid dosing) Phase 2 results BPX-601 Amend BP-012 to allow for scheduled 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 MAA Approval C/CP-004 trials rimiducid for pediatric patients Rivo-cel THRIVE Phase 2 interim data 31
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, gastric and prostate cancers ▪ Late interim results presented at ASH in Dec. 2018 trend ▪ toward meeting primary endpoint Initial safety data on 12 pancreatic patients presented at ESMO- ▪ IO in Dec. 2018 indicate attractive safety profile and early clinical Expect topline data in 1H 2019; MAA filings in 2H 2019 activity ▪ European HQ and leadership team in place for ▪ Trial amendments to lymphodepletion regimen and activation commercialization prep molecule administration to 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 of $98.0MM as of December 31, 2018; Cash Runway Through 2019 32