Biolinerx Ltd. · TASE:BLRX
Biolinerx — Technical Presentation (December 2020)
49 slides from Biolinerx's technical presentation, Dec 16, 2020
Slide 1: KOL Webinar to Discuss Final Results from COMBAT/KEYNOTE-202 Phase 2a Study
Transforming science into medicine KOL Webinar to Discuss Final Results from COMBAT/KEYNOTE-202 Phase 2a Study in Metastatic Pancreatic CancerDecember 16, 2020
Slide 2: Forward-Looking Statements
Forward-Looking Statements Various statements in this presentation concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "b
Slide 3: Featured KOLs
Featured KOLs Gulam Manji, M.D., Ph.D. is an Assistant Professor of Medicine and Director of Medical Oncology & Translational Research for The Pancreas Center at Columbia University Medical Center. Dr. Manji completed his PhD from the University of Wisconsin-Madison and Internal Medicine Residency a
Slide 4: Agenda
Agenda Philip Serlin, Chief Executive Officer, BioLineRx – Introductory commentsGulam Abbas Manji, MD/PhDDr. Golan Talia Golan, MDManuel Hidalgo, M.D., Ph.D.Q&APhilip Serlin – Closing remarks
Slide 5: Targeting CXCR4 with combination chemotherapy and immunotherapy in Pancreas Ductal Adenocarcinoma
Targeting CXCR4 with combination chemotherapy and immunotherapy in Pancreas Ductal Adenocarcinoma Gulam Abbas Manji, MD/PhDAssistant Professor, Division of Hematology and OncologyDirector of Pancreas Medical Oncology and Translational MedicineColumbia University Irving Medical CenterDecember 16, 202
Slide 6: Disclosures
Research FundingGenentech/Roche Merck BioLineRxRegeneronPlexxikonAdvisory RoleGenentech/RocheBioLineRxIpsen Disclosures
Slide 7: Immune Checkpoint Blockade and Pancreas Cancer
Immune Checkpoint Blockade (ICB) and Pancreas Cancer PDL1 and TILRetrospective – Resected PDA (N=51) Nomi, T. CCR. 2007; 13:251-7
Slide 8: CXCR4 inhibition Leads to Tumor Stabilization - Preclinical
CXCR4 inhibition Leads to Tumor Stabilization - Preclinical Feig C, et al. PNAS. 2013. 110:20212-7 CXCL12 CXCR4 CAFS Neoplastic CTLs KPC Mice
Slide 9: CXCR4 inhibition Leads to T-cell Infiltration
Feig C, et al. PNAS. 2013. 110:20212-7 CXCR4 inhibition (CXCR4i) Leads to T-cell Infiltration
Slide 10: CXCL12 Colocalizes with Tumor Cells in Pancreatic Cancer
CXCL12 Colocalizes with Tumor Cells in Pancreatic Cancer Biasci D, et al. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28960-28970. NCT03277209 – Dose escalation of continuous IV administration of AMD3100Treatment resistant MSS CRC and PDAC
Slide 11: CXCR4i Increases CD8 T-cell Infiltration
CXCR4i Increases CD8 T-cell Infiltration Biasci D, et al. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28960-28970. Paired Biopsy CD8+ T cells Plasma ctDNA Plasma CXCL8
Slide 12: CXCR4i, ICB, & Gemcitabine Improve Survival - Preclinical
29.5d vs. 20d (p 0.0148) CXCR4i aPD1 aPD1 CXCR4i Gem CXCR4i CXCR4i Gem aPD1 Gem aPD1 CXCR4i, ICB, & Gemcitabine Improve Survival - Preclinical Manji GA and K Olive, Unpublished
Slide 13: Chemotherapy Enhances Efficacy of CXCR4i and ICB
DCR = 50% KPC Mice DCR = 34.5% DCR = 70% KPC Mice DCR = 63.2% Chemotherapy Enhances Efficacy of CXCR4i and ICB Bockorny B et al. Nature Medicine. 26, pages878–885(2020) Manji GA and K Olive, Unpublished
Slide 14: CXCR4i Improves Tumor Immune Profile
CXCR4i Improves Tumor Immune Profile Bockorny B et al. Nature Medicine. 26, pages878–885(2020) Manji GA and K Olive, Unpublished Pre-trt Post-trt Pre-trt Post-trt DAPICK19CD8CD3FoxP3 KPC Mice Triple Therapy Human – COMBAT Study-dual combination
Slide 15: Chemotherapy, CXCR4i and ICB results in T cell clustering
Manji GA and Rabadan R, Unpublished Chemotherapy, CXCR4i and ICB results in T cell clustering More Clustered More Dispersed Cytotoxic T Cell Tumor Cell x x p = 0.0067 Kruskal test: p = 1.4e-5 Distance from tumor cell to nearest CTL Log Distance (mm) 40m 10m Triple Gem aPD1/CX4i
Slide 16: Summary
Summary Inhibition of CXCR4 in combination with chemotherapy and ICB in KPC mice –Increases CD 8+ T cell/FoxP3+ Improves proximity of CD8+ T cells to neoplastic cellsImproves survivalInhibition of CXCR4 in patients with pancreas cancer –Increases CD8+ T cells (AM3100 and Motixafortide with ICB)Decre
Slide 17: Updates in PDAC
Updates in PDAC Talia Golan, MDMedical Director, Phase I Program & Sheba Pancreatic Cancer Program Sheba Medical Center, Israel December 2020 *
Slide 18: Disclosures
Disclosures Receipt of grants/research supports: Astra Zeneca and MSD MerckReceipt of honoraria or consultation fees: Abbvie, BioLineRx, MSD Merck, Bayer and Teva *
Slide 19: Agenda
Agenda » The current state of pancreatic cancer treatment » Benchmarks for PDAC » Immunotherapy in pancreatic cancer » Summary 19
Slide 20: The majority of PDAC patients are diagnosed with metastatic disease
* The majority of PDAC patients are diagnosed with metastatic disease https://seer.cancer.gov/statfacts/html/pancreas.html
Slide 21: The current state of pancreatic cancer treatment
The current state of pancreatic cancer treatment
Slide 22: Pancreatic cancer deaths are projected to increase
* Pancreatic cancer is the only one of the top 5 cancer killers for which deaths are projected to increase Within this decade, pancreatic cancer will becomethe 2nd leading cause of cancer death in the United States 160 120 80 40 0 2010 2020 2030 PROJECTED CANCER DEATHS Projected cancer deaths (thous
Slide 23: Multiple Drugs and Targets Have Failed in Clinical Trials
Multiple Drugs and Targets Have Failed in Clinical Trials PDAC: Dec 2015 – Dec 2020 Drug Target/Mechanism Phase Number of Patients Evofosfamide Alkylator (Hypoxia) III 694 Ruxolitinib JAK1/2 III Early termination Necuparanib Heparan mimetic I/II 128 Masitinib TKI (Kit, Lyn, Fyn) III 353 Vandetanib T
Slide 24: Therapeutics in advanced PDAC Over Decades
* Therapeutics in advanced PDAC Over 2 Decades Gemcitabinea Erlotinibb FOLFIRINOXc Nab-paclitaxel & gemcitabined LiposomalIrinotecan (Nal-Iri)e A Burris HA JCO 1997b Moore M, JCO 2007C Conroy T NEJM 2011D Von Hoff DD NEJM 2013E Wang-Gillam A Lancet 2016f Le et al Science; 2017G Drilon et al NEJM 201
Slide 25: Benchmark for Pancreatic Cancer
Benchmark for Pancreatic Cancer
Slide 26: Unmet need in first-line treatment of pancreatic cancer
* There is a significant unmet need to prolong disease control and survival as part of first-line treatment for patients with pancreatic cancer mPFS values in graphic; mPFS varies between studies due to study design, inclusion/exclusion criteria and patient demographics. 5-FU=5-flurouracil.1. Burris
Slide 27: Unmet need in second-line treatment of pancreatic cancer
mOS: 4.7 mos * There is also an unmet need to prolong survival in second line treatment for patients with pancreatic cancer mPFS values in graphic; mPFS varies between studies due to study design, inclusion/exclusion criteria and patient demographics. 5-FU=5-flurouracil.1. Wang Gillam et al EJC 2016
Slide 28: Summary Pancreatic Cancer Benchmark for 2L PDAC
Summary Pancreatic Cancer Benchmark for 2L PDACDiagnosed at Metastatic Stage * Endpoint NAPOLI-1stage IV at diagnosis subgroup (n=61) Meta-analysis IRI based 2L (7 studies n=396 )Includes all stages at diagnosis mOS (mos) 4.7 5.5 mPFS (mos) 3.1(stage III-IV n=117) 2.7 ORR (%) 16% 8.7% cORR (%) 7.7%
Slide 29: Immunotherapy in pancreatic cancer
Immunotherapy in pancreatic cancer
Slide 30: Immunotherapy for Pancreatic Cancer
Immunotherapy for Pancreatic Cancer Pancreatic cancer has been regarded as non-immunogenicimmunosuppressive cells and cytokineslow tumor mutational burden paucity of T cells in tumor (number and function)?? Controversial since recent studies demonstrate that the majority of primary tumors are infilt
Slide 31: Durvalumab with or without tremelimumab in 2nd line did not work
PD-1 inhibitor (durvalumab) with or without CTLA4 inhibitor (tremelimumab) in 2nd line : did not work! O’Reilly et al, ASCO GI, 2018
Slide 32: Checkpoint inhibitor plus chemotherapy did not improve first-line efficacy
Combination of Checkpoint inhibitor and chemotherapy did not improve the chemotherapy efficacy in first line Renouf et al, ESMO 2020
Slide 33: Triple combination approaches are promising in PDAC
Triple combination approaches are promising in PDACAPX005M (CD40 agonist) mAb together with gemcitabine/nabpaclitaxel +/- nivolumab as 1st Line treatment O’Hara, et al, Parker Institute, AACR 2019 Overall response rate 54%In all four combo 67%
Slide 34: Summary
Cytotoxic therapy is the mainstay of systemic therapy resulting in modest benefit in pancreatic cancerSingle molecule/pathway targeting is unlikely to result in significant clinical benefitSingle-agent therapeutic approaches focusing on overcoming T-cell immunologic endpoints with immune checkpoint
Slide 35: COMBAT Study - Cohort results
December 16th 2020 COMBAT Study- Cohort 2 resultsManuel Hidalgo, M.D., Ph.D. COMBAT Study Principal Investigator
Slide 36: Disclosure
Disclosure Founder and Stockholder: Champions Oncology, Inc; Nelum PharmaceuticalsStockholder: Agenus, Pharmacyte, InxMed, BioOncotechResearch support from: Erytech, BioExcell, TopAlliance, PanCanHonorarium from: Agenus, Oncomatrix, InxMed, Takeda, PanCan, AACR, Tolero Pharmaceuticals.Royalties: Myr
Slide 37: COMBAT - Study Design
COMBAT - Study Design * Main inclusion/exclusion criteria18 years old and aboveMetastatic disease at first diagnosis (Stage IV) Progressed after first-line gemcitabine-based treatmentNo previous surgeries for PDAC, no previous locally advanced diseaseNo prior PD-1 or PD-L1 treatment EndpointsORR acc
Slide 38: Disposition
Disposition * Assessed for eligibility N=55 Screening Failures N=12 Enrolled N=43Received monotherapy N= 43Received combination N=39Evaluable for efficacy N=38 Non-EvaluableDiscontinued on Monotherapy due to AE N=4Lost to FU N=1 Analysis setITT for Safety N=43Evaluable for efficacy N=38
Slide 39: Baseline characteristics
Baseline characteristics * EVALUABLE N=43 Gender Female 44.2%/Male 55.8% Diagnosed at stage 4 97.6% Median age 68 (40-85) ECOG 0/1 31.3%/68.7% % of MSI-H (MSS status tested in 38 subjects) 0% % of Patients with Liver Metastasis 74.4%
Slide 40: Safety profile
Safety profile * Adverse events reported in >20% of patients ALL Grade≥ 3 Nausea and vomiting 74.4% 18.6% Asthenia 67.4% 16.3% Injection site reactions 55.8% 4.7% Diarrhea 53.5% 14% Appetite disorders 41.9% 9.3% Pruritus 39.5% -- Anemias 37.2% 11.6% Rashes, eruptions and exanthems 30.2% -- Gastroint
Slide 41: COMBAT/Keynote-202 Cohort 2 - Change from Baseline in Target lesions
COMBAT/Keynote-202 Cohort 2-Change from Baseline in Target lesions (N=38) * COMBAT Cohort 2 ORR (%) 21.1% cORR (%) 13.2% SD 42.1% DCR (%) 63.2%
Slide 42: COMBAT/Keynote-202 Cohort 2 - Change from Baseline in Target lesions
COMBAT/Keynote-202 Cohort 2-Change from Baseline in Target lesions (N=38) * Progression Partial Response Stable Disease
Slide 43: COMBAT/Keynote-202 Cohort Median Progression Free Survival
COMBAT/Keynote-202 Cohort 2 Median Progression Free Survival (mPFS) (N=38) *
Slide 44: COMBAT/Keynote-202 Cohort 2 - Duration of Clinical benefit
COMBAT/Keynote-202 Cohort 2- Duration of Clinical benefit *
Slide 45: COMBAT/Keynote-202 Cohort Median Overall Survival
COMBAT/Keynote-202 Cohort 2 Median Overall Survival (mOS) (N=38) *
Slide 46: Safety - Low incidence of Neutropenia and Infections
Safety- Low incidence of Neutropenia and Infections COMBAT NAPOLI1 Neutropenia >=G3 7% 20% Infections/infestations All Grades 21% 38% Infections/infestations >=G3 7% 17% * https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf The triple combination was generally well toleratedIncid
Slide 47: COMBAT Study Results Showed Improvement Across All Endpoints
COMBAT Study Results Showed Improvement Across All Endpoints * 1. Macarulla Mercade et al, Pancreas 2020;2. Petrelli et al EJC 2017 (Iri-based), 3. Wang Gillam et al EJC 2016; Endpoint COMBAT NAPOLI-1stage IV at diagnosis subgroup (n=61) Meta-analysis IRI based 2L (n=396)Stage III-IV at diagnosis mO
Slide 48: Summary
Summary COMBAT Study results showed improvement across all endpoints Despite the triple combination regimen, the incidence of neutropenia and infection is much lower than with standard chemotherapy The COMBAT results are highly encouraging in light of the extremely challenging population, even among
Slide 49: Q&A and Closing Remarks
Q&A and Closing Remarks