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Transforming Science into Medicine
Corporate PresentationOctober 2021
2 Forward-Looking Statements2
This presentation contains “forward-looking statements.” These statements include words like “may,”
“expects,” “believes,” “plans,” “scheduled,” 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.
3 Who are We?3
NASDAQ: BLRX
Ticker / Exchange BLRX (NASDAQ)
Headquarters Tel Aviv, Israel
Market cap ~$140 million (15-Oct-21)
Shares outstanding ~47.3 million (American Depositary Shares)
Cash ~$66 million (30-Jun-21)
Cash runway H1 2024
Employees ~40 (30 in R&D)
4 Investment Highlights4
Multiple opportunities for value enhancement
➢ Final phase 2 PDAC data showed improvement across all endpoints; planning next development steps – randomized study under potential collaborations
➢ Significant milestones over next 12 months, including pre-NDA meeting and NDA submission
Compelling valuation and financial condition
➢ ~$140 million market cap (15-Oct-21)➢ ~$66 million cash as of June 30, 2021➢ Cash runway – H1 2024
Singular focus on novel oncology compounds
➢ Motixafortide (BL-8040) program – phase 3 for SCM completed; in phase 2 for pancreatic cancer and AML
➢ AGI-134 program – in phase 1/2a for solid tumors
SCM – stem cell mobilization; AML – acute myeloid leukemia
Advancing towards potential registration of
Motixafortide in SCM
➢ Positive top-line results from Phase 3 GENESIS trial in SCM; highly statistically significant improvement in all primary and secondary endpoints (p<0.0001)
➢ ~90% of patients transplanted following one dose and one apheresis➢ Company moving forward towards NDA submission in H1 2022
5 Pipeline Targeting Multiple Oncology Indications5
PROGRAM INDICATION PRE-CLINICAL PHASE 1
Stem-cell mobilization
Solid tumors
ONCOLOGYMotixafortide (BL-8040)
AGI-134
Skin lesionsOTHERBL-5010
Pancreatic cancer *
PHASE 3REGULATORY
APPROVALPHASE 2 PARTNERS
*BioLineRx retains all rights to BL-8040 under a clinical trial collaboration with
AML
6
Motixafortide (BL-8040):CXCR4 Antagonist
Oncology Combination Platform for Solid and Hematological Indications
7
Pre-Approval
Stem Cell Mobilization for Multiple Myeloma
Robust mobilization of HSPCs for transplant
Phase 2
Acute Myeloid Leukemia
Mobilization of leukemic cells from bone-marrow protective niche,
sensitization to anti-cancer treatment and induction of
apoptosis
Motixafortide – Best-in-Class CXCR4 Antagonist for Multiple Indications7
Phase 2
Cancer Immunotherapy for Solid Tumors
Mobilization of immune cells to peripheral blood; infiltration of
immune T cells into tumor; reduction of immunosuppression in
tumor microenvironment
HSPC – Hematopoietic stem and progenitor cell
• A 14-amino acid synthetic cyclic peptide, high-affinity CXCR4 antagonist with long receptor occupancy (>48 hours)
• CXCR4 is over-expressed in more than 70% of cancers and its high expression levels correlate with disease severity
• CXCR4 and its ligand CXCL12 (SDF-1) play a critical role in trafficking of CXCR4 expressing cells such as HSPCs, immune and cancer cells
8
Motixafortide in SCM
9
Significant unmet medical need in SCM
• Multiple apheresis sessions required
• 30-50% of patients are poor mobilizers
• For poor mobilizers, 1-4 daily injections of plerixafor on top of G-CSF are required
BL-8040 best-in-class CXCR4 antagonist offers a more effective and convenient mobilization option for all patients
• Robust HSCT mobilization; may support faster engraftment
• Single administration on top of SoC
• Less apheresis sessions and reduced hospitalization costs
SCM for Patients Undergoing Autologous HSC TransplantationPatients with hematological malignancies often require HSC transplant after treatment to restore their immune system
HSC – hematopoietic stem cell; SCM – stem cell mobilizationPlerixafor = Mozobil = AMD3100
9
10 Stem Cell Mobilization OpportunityRare indication showing significant growth and major unmet need
* CIMBTR 2019 Summary Slides (US) – https://www.cibmtr.org/ / EBMT Transplant Activity Survey 2018 Summary (EU) – https://www.ebmt.org/
Growing number of hematopoietic autologous stem-cell transplantations (HSCTs), especially in MM
o An estimated ~45,000 auto-HSCTs were conducted in EU and US in 2018*
o Global potential market estimated at ~$500 million
o ~90% of auto-HSCTs are in MM and lymphomas
o #MM auto-HSCTs is growing (doubled since 2010)
10
54%
36%
10%
Multiple Myeloma
Lymphomas
Other
BL-8040 could become new SoC and expand the market
• BL-8040 could expand beyond poor mobilizers to primary up-front treatment as standard of care
• Potential expansion in other autologous indications, such as lymphomas and sickle cell anemia
11
GENESIS Phase 3Top-Line Results
12
Primary endpoint
• % pts mobilizing ≥6 x 106 CD34+ cells*/kg following single dose of BL-8040 in up to 2 apheresis sessions
Main secondary endpoint
• % pts mobilizing ≥6 x 106 CD34+ cells*/kg following single dose of BL-8040 in 1 apheresis session
Additional secondary endpoints
• Time to neutrophil engraftment
• Time to platelet engraftment
• Time to engraftment defined
GENESIS Phase 3 – Autologous HSCT in MM Pts – Design and Endpoints Randomized (2:1), placebo-controlled, multi-center study in combination with G-CSF, n=122, NCT03246529
Study completed; final results announced May 2021*
* Company announcement: https://ir.biolinerx.com/node/12551/pdf
12
13 >90% of Patients Needed Only ONE Dose of BL-8040 for Transplantation
All patients (N=122)BL-8040+G-CSF
(N=80)Placebo+G-CSF
(N=42)
Treatment effect
Fold increase P value
Based on local lab - actual clinical decision making
92.5% 26.2% 65.1% 3.5 <0.0001
Based on central lab for regulatory purposes
70.0% 14.3% 54.6% 4.9 <0.0001
The primary endpoint: % pts mobilizing ≥6 x 106 CD34+ cells/kg following single dose of BL-8040 in up to 2 aphereses
• 12 sensitivity analyses were done on primary endpoint and all were statistically significant (<0.0001)
13
14
All patients (N=122)BL-8040+G-CSF
(N=80)Placebo+G-CSF
(N=42)
Treatment effect
Fold increase P value
Based on local lab - actual clinical decision making
88.8% 9.5% 78.8% 9.3 <0.0001
Based on central lab for regulatory purposes
67.5% 4.8% 61.7% 14.1 <0.0001
~90% of Patients Needed Only ONE Apheresis for TransplantationPositions Motixafortide on top of G-CSF as SOC upfront mobilization agent
The secondary endpoint: % pts mobilizing ≥6 x 106 CD34+ cells/kg following single dose of BL-8040 in 1 apheresis
14
15 Motixafortide Provides Clear Clinical Differentiation to Plerixafor*Indirect comparison to Plerixafor
Endpoint Study Treatment Arm Placebo Arm Treatment Effect
GENESIS primary endpoint: % of subjects collected ≥ 6x106 CD34+ cells/kg in up to two aphereses
Motixafortide + G-CSF(Single administration)
92.5% 26.2% 65.1%
Plerixafor* + G-CSF(Two Administrations)
71.6% 34.4% 37.2%
GENESIS secondary endpoint: % of subjects collected ≥ 6x106 CD34+ cells/kg in one apheresis
Motixafortide + G-CSF 88.8% 9.5% 78.8%
Plerixafor* + G-CSF 54.2% 17.3% 36.9%
*Indirect comparison; Plerixafor’s efficacy endpoints were calculated using the percentage of CD34+ cells determined by the central laboratory applied to the WBC count from the local laboratory, therefore the correct comparison is to BL-8040’s local lab results. Source: FDA Review
Endpoint Treatment Arm Placebo Arm Treatment Effect
GENESIS primary endpoint 70.0% 14.3% 54.6%
GENESIS secondary endpoint 67.5% 4.8% 61.7%
Regulatory purposes – GENESIS Central Lab
Real-Life Decision-Making – Local Labs
15
16
Higher # cells collected in single apheresis enables transplantation of optimal # of cells, potentiallyproviding significant savings on time to engraftment
Higher # of cells collected also permits cryopreservation for additional transplantation(s)
Certainty regarding number of apheresis sessions required could enable more efficient utilization of apheresis units at transplantation centers
G-CSF + BL-8040 G-CSF+ Placebo
Median # of mobilized cellsin single apheresis
~11M ~2M
Higher # of Cells Mobilized Provides Meaningful Differentiationfor Motixafortide
16
17
Study conducted with IQVIA, alongside very positive Phase 3 GENESIS study, assessed Motixafortide + G-CSF vs. G-CSF alone for SCM in MM patients prior to ASCT
Costs directly associated with primary mobilization
Primary Collection
Costs directly associated with rescue therapy (incl plerixafor)
Rescue Therapy
Cost associated with transplantation (incl length of stay)
Transplantation
Costs and QALY accrued over lifetime (incl previous phases)
Life-long horizon
Health Resource Utilization (HRU) Data Inputs:
Net cost savings:
~$17,000*
* Excludes cost of MotixafortideQALY= Quality adjusted life years
Motixafortide plus G-CSF was associated with a statistically significant HRU decrease during the
ASCT process compared to SoC G-CSF alone
Pharmacoeconomic Study: Motixafortide on Top of G-CSF Demonstrates Significant Cost Benefits
17
Pharmacoeconomic study positions Motixafortide as SOC and demonstrates
commercial viability of Motixafortide in SCM
Leaving substantial room to optimize pricing strategy
18 Motixafortide Provides Clear Differentiation to Current SOC in SCMOne administration, one apheresis, 90% success; significant cost savings
Study met all primary and secondary endpoints with exceptionally high level of statistical significance (p<0.0001)
Combination is safe and tolerable
~90% of patients in treatment arm underwent transplantation following one administration and oneapheresis
Results compare favorably to plerixafor phase 3 results*
Higher # of cells collected potentially enables faster engraftment, as well as cryopreservation for additional transplantation(s)
Pharmacoeconomic study positions Motixafortide as SOC and demonstrates commercial viability in SCM
o $17,000 in cost savings# leaves substantial room to optimize pricing strategy
Company working aggressively to gain regulatory approval – plans to submit NDA in H1/22
• Indirect comparison• # not including the cost of Motixafortide
18
19
Motixafortide in Cancer Immunotherapy - PDAC & Solid Tumors
20
PDAC incidence significant and growing: 460K cases WW in 2018, estimated 815K in 2040
Poor outcomes in PDAC:
• 5y survival rate 8-10%, minimal change in last 30y
• Multiple late-stage failures
• >50% PDAC patients diagnosed with (stage IV) disease = COMBAT Cohort 2 population
• 5y survival rate ~3%, mOS of 3-5 months
Lack of efficacious treatment options (in all lines):
• 1L Gem/FOL-based; 2L vice versa
• 2L Onivyde is the only approved regimen
• Immunotherapy has no effect* => need to co-target alternative pathways
2L PDAC represents a multi-billion $ addressable market
• ~85% of patients treated 1L and then 40% 2L
• ~130K 2L pts in major markets#
BL-8040 is the most advanced CXCR4 antagonist in clinical development for PDAC
• Failed trials based on single promising endpoint, while BL-8040 improves multiple endpoints in homogenous population => better prediction of future success
• Plan to expand beyond PDAC 2L into additional treatment lines and other solid tumors (1L PDAC study initiated^)
2L Pancreatic Cancer Market Represents Significant OpportunityCold tumor where IO has no effect; significant market opportunity with high unmet medical need
20
GLOBOCAN 2018; graph produced from WHO Cancer Tomorrow website - link# 2L calculation based on e2025: ~400K Pancreatic cancer pts in major markets (US&CA 68K, Europe 146K, China 146K, JP 47K) - link* Pembro only approved in MSI-H PDAC (~1% of pts) ^ BL-8040/PD-1i/Chemotherapy – NCT04543071
China
Europe
USA+CA
Estimated pancreatic cancer cases # 2018-2040
Japan
21COMBAT Phase 2a Study– Cohort 1: Dual Combination
MoA demonstrated by mono / dual combination (in patient biopsies - representative MultiOmyxTM data*):
o Increased activated cytotoxic T cells
o Decreased myeloid derived suppressor cells in tumormicroenvironment
o Reduction in tumor cell numbers
Supported by 2 additional independent studies#
Phase 2a open-label, multi-center study to assess the safety and efficacy of BL-8040 and pembrolizumab in subjects with metastatic pancreatic cancer: NCT02826486 (n=37)
21
*Representative MultiOmyxTM data taken SD patient and long treatment duration (11 combo cycles ~34 weeks). Data shown before treatment vs. after ~7w of treatment (end of cycle 2)# (1) Fogelman et al, SITC 2009; (2) Morpheus Study, ASCO GI 2020
End
Cyc
le 2
Scre
enin
g
In collaboration with Bockorny et al., Nat Med (2020)Bockorny et al, Clin Cancer Res (2021)
22 Rationale for Motixafortide Triple Combo in Cohort 2Tumors with low immune visibility require multi-modal approach to advance treatment beyond SoC limitations
22
Adapted from Chen and Mellman
Chemotherapy
Motixafortide (BL-8040)
Checkpoint Inhibitor
Chemotherapy induces tumor death, reducing tumor burden
Chemotherapy induces immunogenic cell death, leading to activation & expansion of new tumor-reactive T-cell clones
Motixafortide facilitates effector T cell mobilization/ trafficking from BM/LN to periphery and infiltration into TME;
Motixafortide facilitates TME modulation: ↑activated CTLs and ↓MDSCs/Tregs
PD1 maintains & restores activity of T cells within tumor
23 Design of Triple Combination – Cohort 2Triple combination: BL-8040 and pembro on top of SOC in 2L PDAC
EndpointsORR according to RECIST 1.1 criteriaDisease control rate (DCR)Duration of responsePFS and OSSafety and tolerability
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
23
Dr Hidalgo, Dec 2020 – KOL Webinar – Link* All n=43, evaluable n=38
Study completed; final results presented in December 2020 *
In collaboration with Bockorny et al., Nat Med (2020)Bockorny et al, Clin Cancer Res (2021)
24
Change from Baseline in Target lesions
Data shown for subjects treated with the triple combination and have at least one Post Monotherapy D5 (BL) Scan
Triple Combo Shows Tumor Shrinkage Over Time (SD→PR)Majority of patients achieved PRs and SDs with triple combo
24
Dr Hidalgo, Dec 2020 – KOL Webinar – Link
Partial
Response
25 Consistent and Meaningful Improvement Across All Study EndpointsDemonstrated in hard-to-treat PDAC patients (caveated by limitations of small single-arm study)
25
# Based on benchmarking conducted – see KOL Webinar Link1 Macarulla Mercade et al, Pancreas 2020; 2 Petrelli et al Eu J Cancer 2017; 3 Onivyde SMPC; 4 Wang Gillam Eu J cancer 2019
Summary of COMBAT Results
COMBAT 2 data showed improvement across all efficacy parameters compared to best matching population benchmark
Prolonged mOS and mPFS
Improved Confirmed ORR
Responses and stable disease were generally durable
Favorable safety compared to Onivyde label
COMBAT HISTORICAL DATA#
mOS 6.5 months 4.7 months1
mPFS 4.0 months 2.7-3.1 months2,3
cORR 13.2% 7.7%3
DCR 63.2% 29-52%2,4
26
AGI-134Cancer Immunotherapy
Universal Anti-Cancer Vaccine with Unique MoA
27 What is the Alpha-Gal and Anti-Gal Story?27
Xenotransplantation experiments in the 1980’s-90’s found that, when introduced to humans, the alpha-Gal-positive tissue was bound by pre-existing human anti-Gal antibodies, which were the main cause of the rejection of porcine heart valves
AGI-134 coats tumor cells with alpha-Gal to make them look like foreign tissue and harness the pre-existing immune machinery, to evoke an immune response against the tumor
AGI-134: a fully synthetic alpha-Gal glycolipid for IT injection
a-Gal linker phospholipid
28 AGI-134 – Mechanism of Action28
AGI-134 directs pre-existing anti-Gal antibodies to the tumor and induces activation of multiple immune system effector arms against the patient’s own neoantigens
29AGI-134 Monotherapy - Phase 1/2a Study DesignPart 1 successfully completed
Endpoints
Safety and tolerability
Determine MTD and RP2D
Pharmacodynamic and biomarker assessments
29
PART 1 PART 2
Monotherapy Expansion
25mg 50mg 100mg 200mg3 Deep Lesions Deep & Superficial Lesions
1
32
1 1
3
2
Accelerated Escalation MonotherapyAccelerated Dose Escalation Dose Expansion
Open-label study to evaluate the safety and tolerability of AGI-134 intratumoral as a monotherapy, in unresectable/metastatic solid tumors (NCT03593226) (n=40)
• Part 1 of study successfully completed - AGI-134 was found to be safe and well tolerated with no dose-limiting toxicities observed
• Part 2 initial results expected H2 2021
30
Looking Ahead
31 Upcoming Major Clinical and Regulatory Milestones in Next 12 Months31
BL-8040 Pharmacoeconomic study results in SCM H2 2021
BL-8040 Pre-NDA meeting with FDA (SCM) H2 2021
AGI-134 Initial results from part 2 of Phase 1/2a trial H2 2021
BL-8040 NDA submission (SCM) H1 2022
√
32 Investment Summary32
Multiple opportunities for value enhancement
➢ Final phase 2 PDAC data showed improvement across all endpoints; planning next development steps – randomized study under potential collaborations
➢ Significant milestones over next 12 months, including pre-NDA meeting and NDA submission
Compelling valuation and financial condition
➢ ~$140 million market cap (15-Oct-21)➢ ~$66 million cash as of June 30, 2021➢ Cash runway – H1 2024
Singular focus on novel oncology compounds
➢ Motixafortide (BL-8040) program – phase 3 for SCM completed; in phase 2 for pancreatic cancer and AML
➢ AGI-134 program – in phase 1/2a for solid tumors
SCM – stem cell mobilization; AML – acute myeloid leukemia
Advancing towards potential registration of
Motixafortide in SCM
➢ Positive top-line results from Phase 3 GENESIS trial in SCM; highly statistically significant improvement in all primary and secondary endpoints (p<0.0001)
➢ ~90% of patients transplanted following one dose and one apheresis➢ Company moving forward towards NDA submission in H1 2022
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