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In this report, “we,” “us” and “our” refer to Bellicum Pharmaceuticals, Inc.
| Item 8.01 | Other Events. |
On February 9, 2021 we made available on our corporate website an updated corporate presentation, in connection with our previous announcement that, on January 28, 2021, the U.S. Food and Drug Administration lifted the clinical hold on patient enrollment and dosing in our ongoing Phase 1/2 dose-escalation clinical trial evaluating BPX-601 and rimiducid in patients with previously treated metastatic pancreatic or prostate cancer. A copy of the corporate presentation is attached hereto as Exhibit 99.1.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
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| 99.1 | Corporate presentation. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
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: February 9, 2021 | By: | /s/ Richard A. Fair | ||||
| Richard A. Fair | ||||||
| President and Chief Executive Officer | ||||||
Exhibit 99.1 Investor Presentation Building a powerful new future in cellular IO February 2021Exhibit 99.1 Investor Presentation Building a powerful new future in cellular IO February 2021
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 GoCAR™ platform, and related technologies; our product candidates including BPX-601, BPX-603, and rimiducid; the timing and success of our current and planned clinical trials, including the timing of receipt of data from such clinical trials and the timing of our reports of such data; the possible range of applications of our cell therapy programs and potential curative effects and safety in the treatment of diseases, including as compared to other treatment options and competitive therapies; and our near-term restructuring plan, including focus of our clinical and research and development activities, reduction in employee headcount and reduction in cash utilization. Our estimates, projections and other forward-looking statements are based on 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, 2019 and our quarterly report on Form 10-Q for the period ended September 30, 2020. 2Forward Looking Statement This presentation contains estimates, projections and other forward-looking statements, concerning, among other things: our research and development activities relating to our GoCAR™ platform, and related technologies; our product candidates including BPX-601, BPX-603, and rimiducid; the timing and success of our current and planned clinical trials, including the timing of receipt of data from such clinical trials and the timing of our reports of such data; the possible range of applications of our cell therapy programs and potential curative effects and safety in the treatment of diseases, including as compared to other treatment options and competitive therapies; and our near-term restructuring plan, including focus of our clinical and research and development activities, reduction in employee headcount and reduction in cash utilization. Our estimates, projections and other forward-looking statements are based on 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, 2019 and our quarterly report on Form 10-Q for the period ended September 30, 2020. 2
Building a Powerful New Future in Cellular IO Our GoCAR platform is engineered to break through the limitations of current cell therapies Persistence Proliferation Enhances effector cell Boosts effector cell functional persistence by proliferation and extends resisting exhaustion and survival, potentially inhibitory signals from leading to more durable the tumor environment responses Power Re-ignites the host Performance immune response, Molecular switch unleashing the power to technology enables combat tumor tolerance superior control over and intensify tumor GoCAR cells killing 3Building a Powerful New Future in Cellular IO Our GoCAR platform is engineered to break through the limitations of current cell therapies Persistence Proliferation Enhances effector cell Boosts effector cell functional persistence by proliferation and extends resisting exhaustion and survival, potentially inhibitory signals from leading to more durable the tumor environment responses Power Re-ignites the host Performance immune response, Molecular switch unleashing the power to technology enables combat tumor tolerance superior control over and intensify tumor GoCAR cells killing 3
Product Pipeline Establishing the clinical value of GoCAR-T in solid tumors to propel cellular IO forward Clinical Product Candidate Discovery IND-Enabling Proof-of-Concept BPX-601 PSCA+ Pancreatic Cancer Castration-Resistant Prostate Cancer PSCA GoCAR-T BPX-603 HER2+ Solid Tumors HER2 GoCAR-T (Dual-Switch) 4Product Pipeline Establishing the clinical value of GoCAR-T in solid tumors to propel cellular IO forward Clinical Product Candidate Discovery IND-Enabling Proof-of-Concept BPX-601 PSCA+ Pancreatic Cancer Castration-Resistant Prostate Cancer PSCA GoCAR-T BPX-603 HER2+ Solid Tumors HER2 GoCAR-T (Dual-Switch) 4
Technology Overview 5Technology Overview 5
GoCAR: Differentiated Technology Platform Current Generation CAR Technology Next Generation GoCAR Technology Rimiducid Inducible MyD88/CD40 ”iMC” 6GoCAR: Differentiated Technology Platform Current Generation CAR Technology Next Generation GoCAR Technology Rimiducid Inducible MyD88/CD40 ”iMC” 6
GoCAR Proliferation: Superior Expansion and Resistance to T Cell Exhaustion iMC activation limits T cell dysfunction in repeat tumor stimulation exhaustion assay T cell IL-2 production T cell expansion HER2+ 100 100000 tumor cells BPX-603 + Rim 10000 BPX-603 + Rim NT NT 1000 Repeat HER2.z HER2.z 10 tumor HER2.BB.z HER2.BB.z exposure 100 HER2.28.z HER2.28.z BPX-603 BPX-603 BPX-603 + Rim 10 BPX-603 + Rim 1 1 0 2 4 1 2 3 4 Functional Stimulation number Stimulation number assays 7 Fold-expansion IL-2 production (pg/ml)GoCAR Proliferation: Superior Expansion and Resistance to T Cell Exhaustion iMC activation limits T cell dysfunction in repeat tumor stimulation exhaustion assay T cell IL-2 production T cell expansion HER2+ 100 100000 tumor cells BPX-603 + Rim 10000 BPX-603 + Rim NT NT 1000 Repeat HER2.z HER2.z 10 tumor HER2.BB.z HER2.BB.z exposure 100 HER2.28.z HER2.28.z BPX-603 BPX-603 BPX-603 + Rim 10 BPX-603 + Rim 1 1 0 2 4 1 2 3 4 Functional Stimulation number Stimulation number assays 7 Fold-expansion IL-2 production (pg/ml)
GoCAR Persistence: Resistance to Immune Suppressive TME iMC overrides common inhibitory molecules in the tumor microenvironment TGF-b PD-L1 Inhibitory TME 140 35 BPX-601 + Rim BPX-601 + Rim 120 30 M2 MF 25 100 PGE MDSC 2 80 BPX-601 20 BPX-601 BPX-601 + PD-L1 BPX-601 + TGF-b 60 15 PD-L1 BPX-601 + TGF-b BPX-601 + PD-L1 10 40 + Rim + Rim TGF-b ↓ Inhibition 20 5 ↓ Inhibition 0 0 0 100 200 0 100 200 Culture time (hours) Culture time (hours) TME – tumor microenvironment 8 CAR-T proliferation index CAR-T proliferation indexGoCAR Persistence: Resistance to Immune Suppressive TME iMC overrides common inhibitory molecules in the tumor microenvironment TGF-b PD-L1 Inhibitory TME 140 35 BPX-601 + Rim BPX-601 + Rim 120 30 M2 MF 25 100 PGE MDSC 2 80 BPX-601 20 BPX-601 BPX-601 + PD-L1 BPX-601 + TGF-b 60 15 PD-L1 BPX-601 + TGF-b BPX-601 + PD-L1 10 40 + Rim + Rim TGF-b ↓ Inhibition 20 5 ↓ Inhibition 0 0 0 100 200 0 100 200 Culture time (hours) Culture time (hours) TME – tumor microenvironment 8 CAR-T proliferation index CAR-T proliferation index
BPX-601 PSCA GoCAR-T 9BPX-601 PSCA GoCAR-T 9
BPX-601 GoCAR-T Targets Solid Tumors Expressing PSCA Unmet Need Product Profile Summary 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 Status Update Incidence Deaths (U.S.) PSCA (U.S.) ▪ FDA Clinical Hold removed January 28, 2021 Prostate 165k 29k 75-90% ▪ Dose escalation in previously treated mCRPC being initiated at Pancreatic 55k 44k ~50% 5m cells/kg followed by single-dose rimiducid 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 10BPX-601 GoCAR-T Targets Solid Tumors Expressing PSCA Unmet Need Product Profile Summary 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 Status Update Incidence Deaths (U.S.) PSCA (U.S.) ▪ FDA Clinical Hold removed January 28, 2021 Prostate 165k 29k 75-90% ▪ Dose escalation in previously treated mCRPC being initiated at Pancreatic 55k 44k ~50% 5m cells/kg followed by single-dose rimiducid 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 Dose escalation in relapsed/refractory pancreatic cancer Dose Standard Lead-in Repeat Rimiducid Lead-In & Dose Escalation Escalation Conditioning (Cohort 0) (Cohort 5C) (Cohorts 3, 4, 5A) (Cohort 5B) Conservatively designed to evaluate safety • Lead-in cohort with cells only Pancreatic Patient • Partial conditioning with Cytoxan 2L to 6L 2L to 6L 2L 2L Population monotherapy • Single dose of rimiducid to activate iMC BPX-601 Dose 1.25 1.25, 2.5, 5.0 5.0 5.0 6 x10 cells/kg @ Day 0 Standard Conditioning Cohort (5B) • Evaluated safety of standard Flu/Cy 2 2 Cytoxan 0.5g/m Cytoxan 0.5g/m regimen with GoCAR-T 2 2 Cytoxan 1g/m Cytoxan 1g/m Fludarabine Fludarabine • Single dose of rimiducid to activate iMC Conditioning 2 2 @ Day -3 @ Day -3 30mg/m 30mg/m @ Days -5, -4, -3 @ Days -5, -4, -3 Repeat Rimiducid Cohort (5C) • First data using iMC repeatedly as Weekly dosing designed Rimiducid Dose None Single dose Day 7 Single dose Day 7 starting at Day 7 ClinicalTrials.gov Identifier: NCT02744287 11BPX-601: Phase 1 Trial Dose escalation in relapsed/refractory pancreatic cancer Dose Standard Lead-in Repeat Rimiducid Lead-In & Dose Escalation Escalation Conditioning (Cohort 0) (Cohort 5C) (Cohorts 3, 4, 5A) (Cohort 5B) Conservatively designed to evaluate safety • Lead-in cohort with cells only Pancreatic Patient • Partial conditioning with Cytoxan 2L to 6L 2L to 6L 2L 2L Population monotherapy • Single dose of rimiducid to activate iMC BPX-601 Dose 1.25 1.25, 2.5, 5.0 5.0 5.0 6 x10 cells/kg @ Day 0 Standard Conditioning Cohort (5B) • Evaluated safety of standard Flu/Cy 2 2 Cytoxan 0.5g/m Cytoxan 0.5g/m regimen with GoCAR-T 2 2 Cytoxan 1g/m Cytoxan 1g/m Fludarabine Fludarabine • Single dose of rimiducid to activate iMC Conditioning 2 2 @ Day -3 @ Day -3 30mg/m 30mg/m @ Days -5, -4, -3 @ Days -5, -4, -3 Repeat Rimiducid Cohort (5C) • First data using iMC repeatedly as Weekly dosing designed Rimiducid Dose None Single dose Day 7 Single dose Day 7 starting at Day 7 ClinicalTrials.gov Identifier: NCT02744287 11
BPX-601: Safety Reported Through Cohort 5C Updated based on data cut December 1, 2020* Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B All Patients Cohort 5C Patients, n (%) n = 3 n = 3 n = 3 n = 4 n = 5 n = 5 n = 23 Any AE 3 (100) 3 (100) 3 (100) 4 (100) 5 (100) 5 (100) 23 (100) ▪ Adverse events (AEs) were generally Any SAE 1 (33) 1 (33) 0 3 (75) 4 (80) 4 (80) 13 (57) consistent with cytotoxic chemotherapy or AEs in >15% of all patients, n (%) other cancer immunotherapies Neutropenia 0 1 (33) 0 3 (75) 4 (80) 3 (60) 11 (48) Febrile neutropenia 0 0 0 2 (50) 4 (80) 2 (40) 8 (35) ▪ AEs related to BPX-601/rimiducid included: Leukopenia 0 0 0 1 (25) 3 (60) 3 (60) 7 (30) Pyrexia 0 0 1 (33) 2 (50) 2 (40) 2 (40) 7 (30) ▪ One case of Grade 2 and one case of Fatigue 2 (67) 1 (33) 0 2 (50) 0 0 5 (22) Grade 4 cytokine release syndrome Anemia 0 0 0 1 (25) 2 (40) 2 (40) 5 (22) (CRS)** Nausea 2 (67) 0 0 0 3 (60) 0 5 (22) Hypotension 0 0 2 (67) 1 (25) 0 2 (40) 5 (22) ▪ One case of Grade 2 encephalopathy Blood bilirubin increased 0 0 0 1 (25) 2 (40) 2 (40) 5 (22) Dysuria 0 0 0 0 4 (80) 0 4 (17) ▪ Five cases of Grade 1-3 urologic toxicity, Hematuria 0 0 0 0 3 (60) 1 (20) 4 (17) Abdominal pain upper 0 1 (33) 0 1 (25) 1 (20) 1 (20) 4 (17) mitigated by prophylactic measures Constipation 0 0 0 2 (50) 1 (20) 1 (20) 4 (17) introduced in Cohort 5C Vomiting 1 (33) 0 0 0 1 (20) 2 (40) 4 (17) Back pain 1 (33) 1 (33) 0 2 (50) 0 0 4 (17) *BPX-601 Investigator’s Brochure v4, December 2020; **Grade 4 CRS reported in one patient (SAE report CIOMS US-BLCM-202000058) 12BPX-601: Safety Reported Through Cohort 5C Updated based on data cut December 1, 2020* Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B All Patients Cohort 5C Patients, n (%) n = 3 n = 3 n = 3 n = 4 n = 5 n = 5 n = 23 Any AE 3 (100) 3 (100) 3 (100) 4 (100) 5 (100) 5 (100) 23 (100) ▪ Adverse events (AEs) were generally Any SAE 1 (33) 1 (33) 0 3 (75) 4 (80) 4 (80) 13 (57) consistent with cytotoxic chemotherapy or AEs in >15% of all patients, n (%) other cancer immunotherapies Neutropenia 0 1 (33) 0 3 (75) 4 (80) 3 (60) 11 (48) Febrile neutropenia 0 0 0 2 (50) 4 (80) 2 (40) 8 (35) ▪ AEs related to BPX-601/rimiducid included: Leukopenia 0 0 0 1 (25) 3 (60) 3 (60) 7 (30) Pyrexia 0 0 1 (33) 2 (50) 2 (40) 2 (40) 7 (30) ▪ One case of Grade 2 and one case of Fatigue 2 (67) 1 (33) 0 2 (50) 0 0 5 (22) Grade 4 cytokine release syndrome Anemia 0 0 0 1 (25) 2 (40) 2 (40) 5 (22) (CRS)** Nausea 2 (67) 0 0 0 3 (60) 0 5 (22) Hypotension 0 0 2 (67) 1 (25) 0 2 (40) 5 (22) ▪ One case of Grade 2 encephalopathy Blood bilirubin increased 0 0 0 1 (25) 2 (40) 2 (40) 5 (22) Dysuria 0 0 0 0 4 (80) 0 4 (17) ▪ Five cases of Grade 1-3 urologic toxicity, Hematuria 0 0 0 0 3 (60) 1 (20) 4 (17) Abdominal pain upper 0 1 (33) 0 1 (25) 1 (20) 1 (20) 4 (17) mitigated by prophylactic measures Constipation 0 0 0 2 (50) 1 (20) 1 (20) 4 (17) introduced in Cohort 5C Vomiting 1 (33) 0 0 0 1 (20) 2 (40) 4 (17) Back pain 1 (33) 1 (33) 0 2 (50) 0 0 4 (17) *BPX-601 Investigator’s Brochure v4, December 2020; **Grade 4 CRS reported in one patient (SAE report CIOMS US-BLCM-202000058) 12
BPX-601: Updated Efficacy Through Cohort 5C Updated based on data cut December 1, 2020* Anti-tumor Activity in ITT Population Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B Overall Cohort 5C Patients, n (%) n = 3 n = 3 n = 3 n = 4 n = 5 n = 5 n = 23 Progressive Disease (PD), n 2 1 1 1 2 1 8 Stable Disease (SD), n 1 2 2 1 3 3 12 Partial Response (PR), n 0 0 0 0 0 0 0 Complete Response (CR), n 0 0 0 0 0 0 0 Disease Control Rate 1 (33) 2 (67) 2 (67) 1 (25) 3 (60) 3 (60) 12 (55) (CR+PR+SD), n(%) ITT population defined as all patients who received BPX-601 and rimiducid and had at least one post-baseline disease evaluation. *BPX-601 Investigator’s Brochure v4, December 2020 13BPX-601: Updated Efficacy Through Cohort 5C Updated based on data cut December 1, 2020* Anti-tumor Activity in ITT Population Cohort 0 Cohort 3 Cohort 4 Cohort 5A Cohort 5B Overall Cohort 5C Patients, n (%) n = 3 n = 3 n = 3 n = 4 n = 5 n = 5 n = 23 Progressive Disease (PD), n 2 1 1 1 2 1 8 Stable Disease (SD), n 1 2 2 1 3 3 12 Partial Response (PR), n 0 0 0 0 0 0 0 Complete Response (CR), n 0 0 0 0 0 0 0 Disease Control Rate 1 (33) 2 (67) 2 (67) 1 (25) 3 (60) 3 (60) 12 (55) (CR+PR+SD), n(%) ITT population defined as all patients who received BPX-601 and rimiducid and had at least one post-baseline disease evaluation. *BPX-601 Investigator’s Brochure v4, December 2020 13
Interim Biomarker Update: BPX-601 Cohort 5C Evidence of repeat rimiducid-mediated CAR-T cell activation was observed • Rimiducid administration was associated with increased serum cytokine levels, including IL-5, TNF-�� , and IFN-�� • Rimiducid treatment was also associated with increased expression of activation markers (e.g. CD25) on peripheral CD4+ and CD8+ T cells, indicative of systemic immune modulation via BPX-601 iMC activation • In two evaluable subjects receiving >2 doses of rimiducid, repeat dosing was not shown to increase peak or AUC circulating BPX- 601 cells relative to single-dose rimiducid • Consistent with previous cohorts, rimiducid administration was associated with a transient decline followed by partial recovery in circulating BPX-601 cells 14Interim Biomarker Update: BPX-601 Cohort 5C Evidence of repeat rimiducid-mediated CAR-T cell activation was observed • Rimiducid administration was associated with increased serum cytokine levels, including IL-5, TNF-�� , and IFN-�� • Rimiducid treatment was also associated with increased expression of activation markers (e.g. CD25) on peripheral CD4+ and CD8+ T cells, indicative of systemic immune modulation via BPX-601 iMC activation • In two evaluable subjects receiving >2 doses of rimiducid, repeat dosing was not shown to increase peak or AUC circulating BPX- 601 cells relative to single-dose rimiducid • Consistent with previous cohorts, rimiducid administration was associated with a transient decline followed by partial recovery in circulating BPX-601 cells 14
BPX-601: GoCAR-T Increased Immunomodulatory Cytokines Infusion of BPX-601 and activation with rimiducid increased immunomodulatory cytokines ▪ Increases in Th1 and Th2 cytokines were observed with: ▪ Administration of BPX- 601 GoCAR-T cells ▪ GoCAR-T activation with rimiducid Shaw et al, ASCO GI 2020 Stacked bars represent the summed mean fold-change in concentration of cytokines in each category in patients from Cohort 5B (n=5). Black dotted line represents the mean VCN for Cohort 5B. Gray dotted line represented rimiducid administration on Day 7. Conc., concentration; Rim, rimiducid. 15 15BPX-601: GoCAR-T Increased Immunomodulatory Cytokines Infusion of BPX-601 and activation with rimiducid increased immunomodulatory cytokines ▪ Increases in Th1 and Th2 cytokines were observed with: ▪ Administration of BPX- 601 GoCAR-T cells ▪ GoCAR-T activation with rimiducid Shaw et al, ASCO GI 2020 Stacked bars represent the summed mean fold-change in concentration of cytokines in each category in patients from Cohort 5B (n=5). Black dotted line represents the mean VCN for Cohort 5B. Gray dotted line represented rimiducid administration on Day 7. Conc., concentration; Rim, rimiducid. 15 15
BPX-601: GoCAR-T Infiltrated Metastatic Pancreatic Tumors On-treatment biopsies taken from metastatic lesions show BPX-601 tumor infiltration BPX-601 Infiltration 5 0 0 ▪ Analysis of tumor metastases from patients 4 0 0 212 showed: T u m o r 3 0 0 ▪ Infiltration of BPX-601 S t r o m a 161 GoCAR-T cells A d j. N o r m a l 2 0 0 ▪ BPX-601 effectively 38 238 77 localized to tumor 1 0 0 119 82 19 0 5 B -2 5 B -4 5 B -5 CD3 = Blue; BPX-601 = Red, arrows Shaw et al, ASCO GI 2020 (Left) Stacked bars represent the total number of BPX-601 cells quantified in ISH stained tissue sections of available (n=3) biopsies from metastatic lesions of Cohort 5B patients. White numbers in bars indicate the number of BPX-601 cells measured within each ROI. (Right) Representative images of CD3 (IHC) and BPX-601 (ISH) stained tissue sections of available (n=3) biopsies from metastatic lesions of Cohort 5B patients. Red arrows indicate BPX-601 GoCAR-T cells 16 Adj. normal, adjacent normal; ROI, region of interest. T o t a l In f ilt r a t in g B P X - 6 0 1 C e llsBPX-601: GoCAR-T Infiltrated Metastatic Pancreatic Tumors On-treatment biopsies taken from metastatic lesions show BPX-601 tumor infiltration BPX-601 Infiltration 5 0 0 ▪ Analysis of tumor metastases from patients 4 0 0 212 showed: T u m o r 3 0 0 ▪ Infiltration of BPX-601 S t r o m a 161 GoCAR-T cells A d j. N o r m a l 2 0 0 ▪ BPX-601 effectively 38 238 77 localized to tumor 1 0 0 119 82 19 0 5 B -2 5 B -4 5 B -5 CD3 = Blue; BPX-601 = Red, arrows Shaw et al, ASCO GI 2020 (Left) Stacked bars represent the total number of BPX-601 cells quantified in ISH stained tissue sections of available (n=3) biopsies from metastatic lesions of Cohort 5B patients. White numbers in bars indicate the number of BPX-601 cells measured within each ROI. (Right) Representative images of CD3 (IHC) and BPX-601 (ISH) stained tissue sections of available (n=3) biopsies from metastatic lesions of Cohort 5B patients. Red arrows indicate BPX-601 GoCAR-T cells 16 Adj. normal, adjacent normal; ROI, region of interest. T o t a l In f ilt r a t in g B P X - 6 0 1 C e lls
BPX-601: Modulation of Tumor Microenvironment Changes in gene expression consistent with productive T cell immune responses ▪ Upregulation of T/CAR-T cell Differentially Expressed Genes in Tumor Metastases After BPX-601 + Rim associated genes including: (Cohort 5B, n=3) ▪ GZMB – Target cell killing by cytotoxic T cells ▪ CXCR3 – Activated T cell trafficking ▪ 41BB(TNFSF9) / 41BBL(TNFRSF9) – T cell costimulation ▪ CD3Z (CD247) – TCR Signaling ▪ STAT1 – Interferon signaling Effector T/ CAR-T Cell▪ BPX-601 – Infiltrating Associated Genes GoCAR-T cells Shaw et al, ASCO GI 2020 17 Box and whisker plots indicate log2 fold change of genes with altered expression (upregulation or downregulation) while on-treatment (Day 14-21) from paired baseline sample (p-value < 10%). nCounter data using NanoString PanCan IO360 panel.BPX-601: Modulation of Tumor Microenvironment Changes in gene expression consistent with productive T cell immune responses ▪ Upregulation of T/CAR-T cell Differentially Expressed Genes in Tumor Metastases After BPX-601 + Rim associated genes including: (Cohort 5B, n=3) ▪ GZMB – Target cell killing by cytotoxic T cells ▪ CXCR3 – Activated T cell trafficking ▪ 41BB(TNFSF9) / 41BBL(TNFRSF9) – T cell costimulation ▪ CD3Z (CD247) – TCR Signaling ▪ STAT1 – Interferon signaling Effector T/ CAR-T Cell▪ BPX-601 – Infiltrating Associated Genes GoCAR-T cells Shaw et al, ASCO GI 2020 17 Box and whisker plots indicate log2 fold change of genes with altered expression (upregulation or downregulation) while on-treatment (Day 14-21) from paired baseline sample (p-value < 10%). nCounter data using NanoString PanCan IO360 panel.
BPX-603 HER-2 GoCAR-T 18BPX-603 HER-2 GoCAR-T 18
BPX-603 Dual Switch GoCAR-T Targeting HER2 Product Profile Summary Unmet Need 5-year OS ▪ HER2 is a validated tumor antigen expressed on numerous 1 + Indication Incidence HER2 1 (Stage IV) solid tumors with high unmet need 3 Gastric 28,000 10-30% <20% ▪ BPX-603 designed to potentially address limitations of 4 previous CAR-T efforts targeting HER2 Colorectal 145,000 10% <15% ▪ Moderate affinity scFv to enhance target engagement and activity 5 Ovarian 22,000 20-30% <30% ▪ MC signaling to increase cell proliferation & persistence, modulate the TME, and enhance host immunity 6 ▪ Bellicum switch technology designed to time and manage CAR-T Uterine/ 61,000 50-80% 14-69% activation and enable mitigation of acute toxicities Endometrial 2 Status Update Glioblastoma 12,000 20-30% <20% • Initial study sites activated; first patient enrolled 7 Breast 271,000 16% 90% 1 2 3 4 National Cancer Database, American Cancer Society, https://www.cancer.org, accessed 21 December 2018; Liu et al., Cancer Res 2004; Gravalos et al., Annals Oncol 2008; Tu et al., Exp Ther Med 2018; 5 6 Berchuck et al., Cancer Res 1990, Bartlett et al., Brit J Cancer 1996; Grushko et al., Gynecologic Oncol 2008, (7) Cronin et al, Cancer Invest. 2010 19BPX-603 Dual Switch GoCAR-T Targeting HER2 Product Profile Summary Unmet Need 5-year OS ▪ HER2 is a validated tumor antigen expressed on numerous 1 + Indication Incidence HER2 1 (Stage IV) solid tumors with high unmet need 3 Gastric 28,000 10-30% <20% ▪ BPX-603 designed to potentially address limitations of 4 previous CAR-T efforts targeting HER2 Colorectal 145,000 10% <15% ▪ Moderate affinity scFv to enhance target engagement and activity 5 Ovarian 22,000 20-30% <30% ▪ MC signaling to increase cell proliferation & persistence, modulate the TME, and enhance host immunity 6 ▪ Bellicum switch technology designed to time and manage CAR-T Uterine/ 61,000 50-80% 14-69% activation and enable mitigation of acute toxicities Endometrial 2 Status Update Glioblastoma 12,000 20-30% <20% • Initial study sites activated; first patient enrolled 7 Breast 271,000 16% 90% 1 2 3 4 National Cancer Database, American Cancer Society, https://www.cancer.org, accessed 21 December 2018; Liu et al., Cancer Res 2004; Gravalos et al., Annals Oncol 2008; Tu et al., Exp Ther Med 2018; 5 6 Berchuck et al., Cancer Res 1990, Bartlett et al., Brit J Cancer 1996; Grushko et al., Gynecologic Oncol 2008, (7) Cronin et al, Cancer Invest. 2010 19
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) 10 4 8 6 6 8 8 CAR-T dose 10 10 - 10 10 10 - 10 10 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) 20Historical 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) 10 4 8 6 6 8 8 CAR-T dose 10 10 - 10 10 10 - 10 10 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) 20
BPX-603: Compelling Preclinical Evidence iMC co-activation enhances cell proliferation Moderate affinity scFv enhances relative to current CAR-T standards anti-tumor effect relative to low affinity FRP5 Tumor growth T cell bioluminescence 10000000 100 10 1000000 BPX-603 + Rim NT 1 FRP5 + Rim 100000 4D5-5 + Rim 0.1 10000 BPX-603 + Rim 0.01 1000 0 5 10 15 20 0 20 40 60 80 Days post-T cell injection Days post-T cell injection 21 Average radiance (p/s/cm2/sr) Average radiance (p/s/cm2/sr)BPX-603: Compelling Preclinical Evidence iMC co-activation enhances cell proliferation Moderate affinity scFv enhances relative to current CAR-T standards anti-tumor effect relative to low affinity FRP5 Tumor growth T cell bioluminescence 10000000 100 10 1000000 BPX-603 + Rim NT 1 FRP5 + Rim 100000 4D5-5 + Rim 0.1 10000 BPX-603 + Rim 0.01 1000 0 5 10 15 20 0 20 40 60 80 Days post-T cell injection Days post-T cell injection 21 Average radiance (p/s/cm2/sr) Average radiance (p/s/cm2/sr)
BPX-603 Phase 1/2 Trial Design Two-Part Safety/Activity Study of HER2-Targeted Dual Switch GoCAR-T Cells in Previously Treated HER2+ Solid Tumors Phase 2: Multi-Arm Dose Expansion in Select Tumor Types Phase 1: 3+3 Dose Escalation Cohort 1: Gastric • Expansion cohorts 10 patients each Locally advanced or • Ability to expand each cohort based on clinical response metastatic HER2+ solid Cohort 2: Breast 1 tumors where standard treatment is no longer If ≥1 response effective, does not exist, 2 or subject is ineligible Starting Dose Cohort 3: Ovarian DL -2 DL -1 DL 1 DL 2 DL 3 DL 4 4 4 5 6 6 6 2.5 x 10 5 x 10 1 x 10 1 x 10 2.5 x 10 5 x 10 Cohort 4: Colorectal Cells/kg 3 Cohort 5: GBM • Sequential patient enrollment - ≥28 days for cohort 1 Cohort 6: Uterine/Endometrial - ≥14 days for subsequent cohorts • First subject in each dose level receives cells only without rimiducid 1 GBM excluded from Phase 1 2 Must include approved HER2-targeted therapy for breast/gastric cancers 22 3 Subjects with GBM will be dosed at recommended dose for expansion (RDE) -1BPX-603 Phase 1/2 Trial Design Two-Part Safety/Activity Study of HER2-Targeted Dual Switch GoCAR-T Cells in Previously Treated HER2+ Solid Tumors Phase 2: Multi-Arm Dose Expansion in Select Tumor Types Phase 1: 3+3 Dose Escalation Cohort 1: Gastric • Expansion cohorts 10 patients each Locally advanced or • Ability to expand each cohort based on clinical response metastatic HER2+ solid Cohort 2: Breast 1 tumors where standard treatment is no longer If ≥1 response effective, does not exist, 2 or subject is ineligible Starting Dose Cohort 3: Ovarian DL -2 DL -1 DL 1 DL 2 DL 3 DL 4 4 4 5 6 6 6 2.5 x 10 5 x 10 1 x 10 1 x 10 2.5 x 10 5 x 10 Cohort 4: Colorectal Cells/kg 3 Cohort 5: GBM • Sequential patient enrollment - ≥28 days for cohort 1 Cohort 6: Uterine/Endometrial - ≥14 days for subsequent cohorts • First subject in each dose level receives cells only without rimiducid 1 GBM excluded from Phase 1 2 Must include approved HER2-targeted therapy for breast/gastric cancers 22 3 Subjects with GBM will be dosed at recommended dose for expansion (RDE) -1
Summary 23Summary 23
Anticipated Key Program Goals & Milestones Goals & Milestones Planned Timing BPX-601 1Q'22 Phase 1 data update in mCRPC Initial Phase 1 data 2H’21 BPX-603 24Anticipated Key Program Goals & Milestones Goals & Milestones Planned Timing BPX-601 1Q'22 Phase 1 data update in mCRPC Initial Phase 1 data 2H’21 BPX-603 24
Investment Summary Building a next generation cell therapy pipeline around the GoCAR platform GoCAR Platform Differentiated co-activation domain (MyD88/CD40) and switch technology drive greater proliferation, persistence, power, and performance BPX-601 BPX-603 • Autologous GoCAR-T targeting PSCA• Autologous Dual-Switch GoCAR-T targeting HER2 in HER2+ solid tumors • Screening for enrollment of a cohort in mCRPC underway• Phase 1/2 trial initiated • Data update planned 1Q'22• First data update planned 2H’2021 Cash runway • Pro forma estimated cash balance of $49.9M as of September 30, 2020; adjusted for net proceeds of +$22.7M from extends into 2Q’22 November 2020 financing and -$27.4M from Oxford Debt Payoff 25Investment Summary Building a next generation cell therapy pipeline around the GoCAR platform GoCAR Platform Differentiated co-activation domain (MyD88/CD40) and switch technology drive greater proliferation, persistence, power, and performance BPX-601 BPX-603 • Autologous GoCAR-T targeting PSCA• Autologous Dual-Switch GoCAR-T targeting HER2 in HER2+ solid tumors • Screening for enrollment of a cohort in mCRPC underway• Phase 1/2 trial initiated • Data update planned 1Q'22• First data update planned 2H’2021 Cash runway • Pro forma estimated cash balance of $49.9M as of September 30, 2020; adjusted for net proceeds of +$22.7M from extends into 2Q’22 November 2020 financing and -$27.4M from Oxford Debt Payoff 25