SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16 OF
THE SECURITIES EXCHANGE ACT OF 1934
For the month of December 2020
Commission file number: 001-35223
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BioLineRx Ltd.
(Translation of registrant’s name into English)
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2 HaMa’ayan Street
Modi’in 7177871, Israel
Modi’in 7177871, Israel
(Address of Principal Executive Offices)
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Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulations S-T Rule 101(b)(1):_____
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulations S-T Rule 101(b)(7):_____
On December 16, 2020, management of the registrant will hold a KOL webinar at 8:00 a.m. ET to discuss the results of the COMBAT/KEYNOTE-202 clinical study. A copy of the presentation being used
in connection with this webinar is furnished herewith as Exhibit 1 to this Report on Form 6-K.
In addition, on December 16, 2020 the registrant issued the press release which is filed as Exhibit 2 to this Report on Form 6-K.
The first, second, and third paragraphs, the table containing the data summary and the paragraph following immediately thereafter in the press release attached to this Form 6-K are hereby
incorporated by reference into all effective registration statements filed by the registrant under the Securities Act of 1933.
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, thereunto duly authorized.
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BioLineRx Ltd.
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By:
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/s/ Philip A. Serlin
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Philip A. Serlin
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Chief Executive Officer
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Dated: December 16, 2020
Exhibit 1
Transforming science into medicine KOL Webinar to Discuss Final Results from COMBAT/KEYNOTE-202 Phase 2a
Study in Metastatic Pancreatic CancerDecember 16, 2020
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," "believes," and "intends," and describe
opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results,
performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not
limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to
successfully complete its preclinical studies or clinical trials; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization
and market acceptance of BioLineRx's therapeutic candidates; BioLineRx's ability to establish and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the
properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for
its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the
intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or
elsewhere; competitive companies, technologies and BioLineRx's industry; risks related to the coronavirus outbreak; and statements as to the impact of the political and security situation in Israel on BioLineRx's business. These and other factors
are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 12, 2020. In addition, any forward-looking statements represent BioLineRx's
views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.
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 at Albany Medical College. He then completed
his fellowship in Hematology/Oncology at New York-Presbyterian/Columbia, where he remained as faculty within the Division of Hematology and Oncology.Talia Golan, M.D. is a highly qualified medical oncologist and researcher in the field of
pancreatic cancer. She specializes in gastrointestinal malignancies and serves as a director of the Phase I clinical trials unit at Sheba’s Pancreatic Cancer Center. She has earned a world-renowned reputation for her studies in the field of
pancreatic cancer. Her current research trials are being carried out in conjunction with two of the world’s largest biopharmaceutical companies, AstraZeneca and MSD (Merck). Manuel Hidalgo, M.D., Ph.D., is currently the Chief of the Division of
Hematology and Medical Oncology at Weill Cornell Medicine/New York-Presbyterian Hospital. Dr. Hidalgo received his M.D. from the University of Navarra in Pamplona, Spain in 1992, and Ph.D. from University Autonoma of Madrid in 1997. He trained in
medicine and medical oncology at Hospital "12 de Octubre" in Madrid and at the University of Texas Health Science Center in San Antonio, Texas. He also completed a fellowship program in anticancer drug development at the Institute of Drug
Development in San Antonio.
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
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, 2020
Research FundingGenentech/Roche Merck BioLineRxRegeneronPlexxikonAdvisory
RoleGenentech/RocheBioLineRxIpsen Disclosures
Immune Checkpoint Blockade (ICB) and Pancreas Cancer PDL1 and TILRetrospective – Resected PDA (N=51)
Nomi, T. CCR. 2007; 13:251-7
CXCR4 inhibition Leads to Tumor Stabilization - Preclinical Feig C, et al. PNAS. 2013. 110:20212-7
CXCL12 CXCR4 CAFS Neoplastic CTLs KPC Mice
Feig C, et al. PNAS. 2013. 110:20212-7 CXCR4 inhibition (CXCR4i) Leads to T-cell Infiltration
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
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
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
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
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
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
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)Decreases MDSCs (Motixafortide with ICB)Encouraging
efficacy in preliminary study with combination with 5-FU, liposomal irinotecan and ICB
Updates in PDAC Talia Golan, MDMedical Director, Phase I Program & Sheba Pancreatic Cancer Program
Sheba Medical Center, Israel December 2020 *
Disclosures Receipt of grants/research supports: Astra Zeneca and MSD MerckReceipt of honoraria or
consultation fees: Abbvie, BioLineRx, MSD Merck, Bayer and Teva *
Agenda *
* The majority of PDAC patients are diagnosed with metastatic
disease https://seer.cancer.gov/statfacts/html/pancreas.html
The current state of pancreatic cancer treatment
* 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
(thousands) LUNG PANCREAS COLORECTAL BREAST PROSTATE
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 TKI
(VEGFR2, RET, EGFR) II 142 Algenpantucel-L Vaccine III 722 CRS-207 + GVAX Vaccine Iib 240 Tarextumab Notch2/3 II 177 Demcizumab DLL4 II 204 90Y-Clivatuzumab
Tetraxetan MUC1 III 334 Apatorsen HSP27 II 132 Z-360 CCK2 II 167 Simtuzumab LOX-2 II 240 (159) MM-141 IGF-1R/ErbB-3 II 88 Ibrutinib BTK III 424 Napabucasin STAT3 III >1,100 Pegilodecakin (AM0010) pegylated IL-10
III 567 PEGPH20 Hyaluron III 500 Cabiralizumab CSFR-1 IIb 160
* 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 2018h Golan et al. NEJM 2019Orange:
chemotherapy and biologicalGreen: biomarker driven targeted therapy Keytruda - MSI-H & dMMR tumorsf Olaparib (BRCAmut)h NTRK- larotrectinibg
Benchmark for 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 HA et al. J Clin Oncol. 1997; 2. Conroy T
et al, NEJM 2011; 3. Von Hoff et al. NEJM 2013 Existing regimens: Time from original diagnosis Months 1 2 3 4 5 6 7 8 9 10 11 12 ORR mFOLFIRINOX2 mOS: 11.1 mos PFS: 6.4 mos Gem/ Abrax3 mOS: 8.5 mos PFS: 5.5 mos Gem2,3 mOS:
5.6-6.7 mos PFS: 3.3-3.7 mos 5FU1 mOS: 4.4 mos PFS: 1 mo
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; 2. Oettle et al, JCO 2014; 3. Macarulla Mercade
et al, Pancreas 2020; 4. Petrelli et al EJC 2017 (Iri-based) Existing regimens: Time from beginning of second line treatment 5FU/LV1 FOLFOX2 5FU/LV+ Onivyde2 stage 3-4 5FU/LV+ OnivydeStage 4 3 Meta-analysis in 2L stage
3-44 Months 1 2 3 4 5 6 7 8 9 10 11 12 Not available ORR mOS: 5.5 mos PFS: 2.7 mos mOS: 6.1 mos PFS: 3.1 mos mOS: 5.9 mos PFS: 2.9 mos mOS: 4.2 mos PFS: 1.5 mos PFS not available cORR Not available Not available Not
available
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% (stage III-IV n=117) NA DCR
(%) 52%(stage III-IV n=117) 29.4% *
Immunotherapy in 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 infiltrated with
T-cellsefficacy of checkpoint inhibitors in PDAC was found to be absentmultiple immune inhibitory mechanisms in the tumor microenvironmentSingle-agent therapeutic approaches focusing on overcoming T-cell immunologic endpoints with immune
checkpoint inhibitors or vaccines are not encouraging Royal RE, et al. J Immunother. 2010;33(8):828-833. Topalian SL, et al. N Engl J Med. 2012;366(26):2443-2454. Morrison AH et al Trends Cancer. 2018;4(6):418-28. Poschke I et al Oncoimmunology.
2016;5(12):e1240859.
PD-1 inhibitor (durvalumab) with or without CTLA4 inhibitor (tremelimumab) in 2nd line : did not
work! O’Reilly et al, ASCO GI, 2018
Combination of Checkpoint inhibitor and chemotherapy did not improve the chemotherapy efficacy in first
line Renouf et al, ESMO 2020
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%
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 inhibitors or vaccines are not
encouragingImmuno combinatorial therapy is the likelier strategy to succeedStrong scientific rationale for which combinations is needed Pancreatic cancer is a tough disease and incremental improvements are clinically meaningful Summary
December 16th 2020 COMBAT Study- Cohort 2 resultsManuel Hidalgo, M.D., Ph.D. COMBAT Study Principal
Investigator
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: Myriad for PALB2
patent.
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 according to RECIST 1.1 criteriaDisease control
rate (DCR)Duration of responsePFS and OSSafety and tolerability
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
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%
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% -- Gastrointestinal
and abdominal pains 30.2% -- Musculoskeletal and connective tissue pain and discomfort 30.2% 4.6% Dermal and epidermal conditions 25.6% -- Edema 23.3% 4.7% Weight decrease 20.9% 2.3% Hyperpigmentation
disorders 20.9% -- Gastrointestinal atonic and hypomotility disorders 20.9% --
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%
COMBAT/Keynote-202 Cohort 2-Change from Baseline in Target lesions (N=38) * Progression Partial
Response Stable Disease
COMBAT/Keynote-202 Cohort 2 Median Progression Free Survival (mPFS) (N=38) *
COMBAT/Keynote-202 Cohort 2- Duration of Clinical benefit *
COMBAT/Keynote-202 Cohort 2 Median Overall Survival (mOS) (N=38) *
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 toleratedIncidence of
AEs is consistent with the profile of each drug, howeverThe incidence of neutropenia and infections is lower than the expected with chemotherapy alone
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 mOS (mos) 6.5 4.7 5.5 mPFS
(mos) 4.0 3.1(stage III-IV n=117) 2.7 ORR (%) 21.2% 16% 8.7% cORR (%) 13.2% 7.7% (stage III-IV n=117) NA DCR (%) 63.2% 52%(stage III-IV n=117) 29.4%
Summary *
Q&A and Closing Remarks