BioLineRx Ltd.
|
|||
|
By:
|
/s/ Philip Serlin | |
Philip Serlin | |||
Chief Executive Officer |
· |
Partial monotherapy results from Phase 2a COMBAT study, investigating the combination of BL-8040 and Merck’s PD-1 inhibitor, Keytruda® (pembrolizumab), in pancreatic cancer, showed significantly increased infiltration of T cells into liver metastases in almost half of the pancreatic cancer patients who underwent a biopsy, as well as an increase in the number of total immune cells in the peripheral blood, alongside a decrease in the frequency of peripheral blood regulatory T cells (Tregs) – all of which support the mechanism of action proposed by pre-clinical studies. Study enrollment has been completed, with top-line results expected in H2 2018;
|
· |
Results from Phase 2 study for BL-8040 as novel stem cell mobilization treatment for allogeneic bone-marrow transplantation support BL-8040 as a one-day dosing regimen for rapid mobilization of stem cells; primary endpoint of collection of ≥2 million CD34 cells/kg recipient weight after up to 2 leukapheresis (LP) sessions was reached in over 90% of patients (100% of patients at optimal BL-8040 dose of 1.25 mg/kg); all 19 transplanted recipients were successfully engrafted with BL-8040-mobilized grafts, and preliminary graft-versus-host disease (GVHD) data are in line with current standard-of-care incidence rates;
|
· |
Overall long-term survival results in Phase 2a trial in relapsed/refractory AML demonstrated that the combination of BL-8040 with high-dose Ara-C (HiDAC) significantly improved overall survival, compared with historical data of HiDAC monotherapy. In the BL-8040 dose selected for expansion (1.5 mg/kg), the overall response rate was 39% (N=23) and median overall survival for this cohort was 9.2 months with 1-year and 2-year survival rates of 31.6% and 21.1%, respectively;
|
· |
Grant of European patent covering use of BL-8040 with Cytarabine for treating AML; valid through March 2034 with up to five years’ patent term extension, thus providing significant additional patent protection in AML, one of BL-8040’s key indications.
|
· |
Pre-clinical data presented at ASCO-SITC showed direct regression of established primary tumors after injection with AGI-134 in the majority of mice treated, and that this regression is associated with activation of the innate immune system;
|
· |
Notice of Allowance issued by the United States Patent and Trademark Office (USPTO) for a patent application claiming the use of AGI-134 for the treatment of solid cancer tumors; this patent, when issued, will be valid until May 2035 with a possibility of up to five years patent term extension. Additional corresponding patent applications for AGI-134 are pending in Europe, Japan, China, Canada, Australia and Israel.
|
· |
Results from the lead-in part of the Phase 3 GENESIS study in stem-cell mobilization for autologous transplantation are due mid-year 2018;
|
· |
Top-line results in immuno-oncology Phase 2a COMBAT study in pancreatic cancer for BL-8040 in combination with KEYTRUDA, under collaboration with Merck, expected in H2 2018;
|
· |
Initiation of Phase 1/2a immuno-oncology study for AGI-134 in several solid tumor indications expected in mid-2018;
|
· |
Additional overall long-term survival data from Phase 2a trial in relapsed/refractory AML to be presented at EHA in June 2018;
|
· |
Full top-line results of Phase 2 study for BL-8040 in stem-cell mobilization for allogeneic transplantation to be presented at the 23rd Congress of European Hematology Association (EHA) in June 2018.
|
December 31,
|
March 31,
|
|||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
Assets
|
||||||||
CURRENT ASSETS
|
||||||||
Cash and cash equivalents
|
5,110
|
7,810
|
||||||
Short-term bank deposits
|
44,373
|
36,388
|
||||||
Prepaid expenses
|
307
|
564
|
||||||
Other receivables
|
586
|
782
|
||||||
Total current assets
|
50,376
|
45,544
|
||||||
NON-CURRENT ASSETS
|
||||||||
Long-term prepaid expenses
|
61
|
60
|
||||||
Long-term investment
|
1,000
|
1,000
|
||||||
Property and equipment, net
|
2,505
|
2,432
|
||||||
Intangible assets, net
|
7,023
|
7,039
|
||||||
Total non-current assets
|
10,589
|
10,531
|
||||||
Total assets
|
60,965
|
56,075
|
||||||
Liabilities and equity
|
||||||||
CURRENT LIABILITIES
|
||||||||
Current maturities of long-term bank loan
|
93
|
93
|
||||||
Accounts payable and accruals:
|
||||||||
Trade
|
5,516
|
4,941
|
||||||
Other
|
1,113
|
1,146
|
||||||
Total current liabilities
|
6,722
|
6,180
|
||||||
NON-CURRENT LIABILITIES
|
||||||||
Long-term bank loan, net of current maturities
|
157
|
133
|
||||||
Warrants
|
1,205
|
740
|
||||||
Total non-current liabilities
|
1,362
|
873
|
||||||
COMMITMENTS AND CONTINGENT LIABILITIES
|
||||||||
Total liabilities
|
8,084
|
7,053
|
||||||
EQUITY
|
||||||||
Ordinary shares
|
2,836
|
2,874
|
||||||
Share premium
|
240,682
|
242,177
|
||||||
Capital reserve
|
10,337
|
11,143
|
||||||
Other comprehensive loss
|
(1,416
|
)
|
(1,416
|
)
|
||||
Accumulated deficit
|
(199,558
|
)
|
(205,756
|
)
|
||||
Total equity
|
52,881
|
49,022
|
||||||
Total liabilities and equity
|
60,965
|
56,075
|
Three months ended March 31,
|
||||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
RESEARCH AND DEVELOPMENT EXPENSES
|
(3,590
|
)
|
(5,070
|
)
|
||||
SALES AND MARKETING EXPENSES
|
(681
|
)
|
(484
|
)
|
||||
GENERAL AND ADMINISTRATIVE EXPENSES
|
(1,030
|
)
|
(1,075
|
)
|
||||
OPERATING LOSS
|
(5,301
|
)
|
(6,629
|
)
|
||||
NON-OPERATING INCOME (EXPENSES), NET
|
(5
|
)
|
462
|
|||||
FINANCIAL INCOME
|
457
|
175
|
||||||
FINANCIAL EXPENSES
|
(6
|
)
|
(206
|
)
|
||||
NET LOSS AND COMPREHENSIVE LOSS
|
(4,855
|
)
|
(6,198
|
)
|
||||
LOSS PER ORDINARY SHARE - BASIC AND DILUTED
|
(0.08
|
)
|
(0.06
|
)
|
||||
WEIGHTED AVERAGE NUMBER OF SHARES USED IN CALCULATION OF LOSS PER ORDINARY SHARE
|
58,620,094
|
106,169,273
|
Ordinary shares
|
Share premium
|
Capital Reserve
|
Other comprehensive loss
|
Accumulated deficit
|
Total
|
|||||||||||||||||||
in USD thousands
|
||||||||||||||||||||||||
BALANCE AT JANUARY 1, 2017
|
1,513
|
199,567
|
10,569
|
(1,416
|
)
|
(175,206
|
)
|
35,027
|
||||||||||||||||
CHANGES FOR THREE MONTHS ENDED MARCH 31, 2017:
|
||||||||||||||||||||||||
Issuance of share capital, net
|
128
|
4,944
|
-
|
-
|
-
|
5,072
|
||||||||||||||||||
Employee stock options exercised
|
1
|
296
|
(297
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Employee stock options forfeited and expired
|
-
|
1,085
|
(1,085
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Share-based compensation
|
-
|
-
|
472
|
-
|
-
|
472
|
||||||||||||||||||
Comprehensive loss for the period
|
-
|
-
|
-
|
-
|
(4,855
|
)
|
(4,855
|
)
|
||||||||||||||||
BALANCE AT MARCH 31, 2017
|
1,642
|
205,892
|
9,659
|
(1,416
|
)
|
(180,061
|
)
|
35,716
|
Ordinary shares
|
Share premium
|
Capital Reserve
|
Other comprehensive loss
|
Accumulated deficit
|
Total
|
|||||||||||||||||||
in USD thousands
|
||||||||||||||||||||||||
BALANCE AT JANUARY 1, 2018
|
2,836
|
240,682
|
10,337
|
(1,416
|
)
|
(199,558
|
)
|
52,881
|
||||||||||||||||
CHANGES FOR THREE MONTHS ENDED MARCH 31, 2018:
|
||||||||||||||||||||||||
Issuance of share capital, net
|
37
|
1,386
|
-
|
-
|
-
|
1,423
|
||||||||||||||||||
Employee stock options exercised
|
1
|
29
|
(30
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Employee stock options forfeited and expired
|
-
|
80
|
(80
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Share-based compensation
|
-
|
-
|
916
|
-
|
-
|
916
|
||||||||||||||||||
Comprehensive loss for the period
|
-
|
-
|
-
|
-
|
(6,198
|
)
|
(6,198
|
)
|
||||||||||||||||
BALANCE AT MARCH 31, 2018
|
2,874
|
242,177
|
11,143
|
(1,416
|
)
|
(205,756
|
)
|
49,022
|
Three months ended
March 31,
|
||||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
CASH FLOWS - OPERATING ACTIVITIES
|
||||||||
Comprehensive loss for the period
|
(4,855
|
)
|
(6,198
|
)
|
||||
Adjustments required to reflect net cash used in operating activities (see appendix below)
|
1,062
|
(609
|
)
|
|||||
Net cash used in operating activities
|
(3,793
|
)
|
(6,807
|
)
|
||||
CASH FLOWS - INVESTING ACTIVITIES
|
||||||||
Investments in short-term deposits
|
(7,013
|
)
|
(4,000
|
)
|
||||
Maturities of short-term deposits
|
12,143
|
12,167
|
||||||
Purchase of property and equipment
|
(45
|
)
|
(54
|
)
|
||||
Purchase of intangible assets
|
(3,718
|
)
|
(29
|
)
|
||||
Net cash provided by investing activities
|
1,367
|
8,084
|
||||||
CASH FLOWS - FINANCING ACTIVITIES
|
||||||||
Issuance of share capital, net of issuance costs
|
2,087
|
1,423
|
||||||
Repayments of bank loan
|
(23
|
)
|
(23
|
)
|
||||
Net cash provided by financing activities
|
2,064
|
1,400
|
||||||
INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS
|
(362
|
)
|
2,677
|
|||||
CASH AND CASH EQUIVALENTS – BEGINNING OF PERIOD
|
2,469
|
5,110
|
||||||
EXCHANGE DIFFERENCES ON CASH AND CASH EQUIVALENTS
|
94
|
23
|
||||||
CASH AND CASH EQUIVALENTS - END OF PERIOD
|
2,201
|
7,810
|
Three months ended
March 31,
|
||||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
Adjustments required to reflect net cash used in operating activities:
|
||||||||
Income and expenses not involving cash flows:
|
||||||||
Depreciation and amortization
|
119
|
140
|
||||||
Long-term prepaid expenses
|
(3
|
)
|
1
|
|||||
Exchange differences on cash and cash equivalents
|
(94
|
)
|
(23
|
)
|
||||
Gain on adjustment of warrants to fair value
|
-
|
(465
|
)
|
|||||
Share-based compensation
|
472
|
916
|
||||||
Interest and exchange differences on short-term deposits
|
(143
|
)
|
(182
|
)
|
||||
Interest and linkage differences on bank loan
|
-
|
(1
|
)
|
|||||
351
|
386
|
|||||||
Changes in operating asset and liability items:
|
||||||||
Increase in prepaid expenses and other receivables
|
(802
|
)
|
(453
|
)
|
||||
Increase (decrease) in accounts payable and accruals
|
1,513
|
(542
|
)
|
|||||
711
|
(995
|
)
|
||||||
1,062
|
(609
|
)
|
||||||
Supplementary information on interest received in cash
|
137
|
167
|
Page
|
||
1
|
||
2
|
||
3
|
||
4-5
|
||
6-8
|
December 31,
|
March 31,
|
|||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
Assets
|
||||||||
CURRENT ASSETS
|
||||||||
Cash and cash equivalents
|
5,110
|
7,810
|
||||||
Short-term bank deposits
|
44,373
|
36,388
|
||||||
Prepaid expenses
|
307
|
564
|
||||||
Other receivables
|
586
|
782
|
||||||
Total current assets
|
50,376
|
45,544
|
||||||
NON-CURRENT ASSETS
|
||||||||
Long-term prepaid expenses
|
61
|
60
|
||||||
Long-term investment
|
1,000
|
1,000
|
||||||
Property and equipment, net
|
2,505
|
2,432
|
||||||
Intangible assets, net
|
7,023
|
7,039
|
||||||
Total non-current assets
|
10,589
|
10,531
|
||||||
Total assets
|
60,965
|
56,075
|
||||||
Liabilities and equity
|
||||||||
CURRENT LIABILITIES
|
||||||||
Current maturities of long-term bank loan
|
93
|
93
|
||||||
Accounts payable and accruals:
|
||||||||
Trade
|
5,516
|
4,941
|
||||||
Other
|
1,113
|
1,146
|
||||||
Total current liabilities
|
6,722
|
6,180
|
||||||
NON-CURRENT LIABILITIES
|
||||||||
Long-term bank loan, net of current maturities
|
157
|
133
|
||||||
Warrants
|
1,205
|
740
|
||||||
Total non-current liabilities
|
1,362
|
873
|
||||||
COMMITMENTS AND CONTINGENT LIABILITIES
|
||||||||
Total liabilities
|
8,084
|
7,053
|
||||||
EQUITY
|
||||||||
Ordinary shares
|
2,836
|
2,874
|
||||||
Share premium
|
240,682
|
242,177
|
||||||
Capital reserve
|
10,337
|
11,143
|
||||||
Other comprehensive loss
|
(1,416
|
)
|
(1,416
|
)
|
||||
Accumulated deficit
|
(199,558
|
)
|
(205,756
|
)
|
||||
Total equity
|
52,881
|
49,022
|
||||||
Total liabilities and equity
|
60,965
|
56,075
|
Three months ended March 31,
|
||||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
RESEARCH AND DEVELOPMENT EXPENSES
|
(3,590
|
)
|
(5,070
|
)
|
||||
SALES AND MARKETING EXPENSES
|
(681
|
)
|
(484
|
)
|
||||
GENERAL AND ADMINISTRATIVE EXPENSES
|
(1,030
|
)
|
(1,075
|
)
|
||||
OPERATING LOSS
|
(5,301
|
)
|
(6,629
|
)
|
||||
NON-OPERATING INCOME (EXPENSES), NET
|
(5
|
)
|
462
|
|||||
FINANCIAL INCOME
|
457
|
175
|
||||||
FINANCIAL EXPENSES
|
(6
|
)
|
(206
|
)
|
||||
NET LOSS AND COMPREHENSIVE LOSS
|
(4,855
|
)
|
(6,198
|
)
|
||||
LOSS PER ORDINARY SHARE - BASIC AND DILUTED
|
(0.08
|
)
|
(0.06
|
)
|
||||
WEIGHTED AVERAGE NUMBER OF SHARES USED IN CALCULATION OF LOSS PER ORDINARY SHARE
|
58,620,094
|
106,169,273
|
Ordinary shares
|
Share premium
|
Capital Reserve
|
Other comprehensive loss
|
Accumulated deficit
|
Total
|
|||||||||||||||||||
in USD thousands
|
||||||||||||||||||||||||
BALANCE AT JANUARY 1, 2017
|
1,513
|
199,567
|
10,569
|
(1,416
|
)
|
(175,206
|
)
|
35,027
|
||||||||||||||||
CHANGES FOR THREE MONTHS ENDED MARCH 31, 2017:
|
||||||||||||||||||||||||
Issuance of share capital, net
|
128
|
4,944
|
-
|
-
|
-
|
5,072
|
||||||||||||||||||
Employee stock options exercised
|
1
|
296
|
(297
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Employee stock options forfeited and expired
|
-
|
1,085
|
(1,085
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Share-based compensation
|
-
|
-
|
472
|
-
|
-
|
472
|
||||||||||||||||||
Comprehensive loss for the period
|
-
|
-
|
-
|
-
|
(4,855
|
)
|
(4,855
|
)
|
||||||||||||||||
BALANCE AT MARCH 31, 2017
|
1,642
|
205,892
|
9,659
|
(1,416
|
)
|
(180,061
|
)
|
35,716
|
Ordinary shares
|
Share premium
|
Capital Reserve
|
Other comprehensive loss
|
Accumulated deficit
|
Total
|
|||||||||||||||||||
in USD thousands
|
||||||||||||||||||||||||
BALANCE AT JANUARY 1, 2018
|
2,836
|
240,682
|
10,337
|
(1,416
|
)
|
(199,558
|
)
|
52,881
|
||||||||||||||||
CHANGES FOR THREE MONTHS ENDED MARCH 31, 2018:
|
||||||||||||||||||||||||
Issuance of share capital, net
|
37
|
1,386
|
-
|
-
|
-
|
1,423
|
||||||||||||||||||
Employee stock options exercised
|
1
|
29
|
(30
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Employee stock options forfeited and expired
|
-
|
80
|
(80
|
)
|
-
|
-
|
-
|
|||||||||||||||||
Share-based compensation
|
-
|
-
|
916
|
-
|
-
|
916
|
||||||||||||||||||
Comprehensive loss for the period
|
-
|
-
|
-
|
-
|
(6,198
|
)
|
(6,198
|
)
|
||||||||||||||||
BALANCE AT MARCH 31, 2018
|
2,874
|
242,177
|
11,143
|
(1,416
|
)
|
(205,756
|
)
|
49,022
|
Three months ended
March 31,
|
||||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
CASH FLOWS - OPERATING ACTIVITIES
|
||||||||
Comprehensive loss for the period
|
(4,855
|
)
|
(6,198
|
)
|
||||
Adjustments required to reflect net cash used in operating activities (see appendix below)
|
1,062
|
(609
|
)
|
|||||
Net cash used in operating activities
|
(3,793
|
)
|
(6,807
|
)
|
||||
CASH FLOWS - INVESTING ACTIVITIES
|
||||||||
Investments in short-term deposits
|
(7,013
|
)
|
(4,000
|
)
|
||||
Maturities of short-term deposits
|
12,143
|
12,167
|
||||||
Purchase of property and equipment
|
(45
|
)
|
(54
|
)
|
||||
Purchase of intangible assets
|
(3,718
|
)
|
(29
|
)
|
||||
Net cash provided by investing activities
|
1,367
|
8,084
|
||||||
CASH FLOWS - FINANCING ACTIVITIES
|
||||||||
Issuance of share capital, net of issuance costs
|
2,087
|
1,423
|
||||||
Repayments of bank loan
|
(23
|
)
|
(23
|
)
|
||||
Net cash provided by financing activities
|
2,064
|
1,400
|
||||||
INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS
|
(362
|
)
|
2,677
|
|||||
CASH AND CASH EQUIVALENTS – BEGINNING OF PERIOD
|
2,469
|
5,110
|
||||||
EXCHANGE DIFFERENCES ON CASH AND CASH EQUIVALENTS
|
94
|
23
|
||||||
CASH AND CASH EQUIVALENTS - END OF PERIOD
|
2,201
|
7,810
|
Three months ended
March 31,
|
||||||||
2017
|
2018
|
|||||||
in USD thousands
|
||||||||
Adjustments required to reflect net cash used in operating activities:
|
||||||||
Income and expenses not involving cash flows:
|
||||||||
Depreciation and amortization
|
119
|
140
|
||||||
Long-term prepaid expenses
|
(3
|
)
|
1
|
|||||
Exchange differences on cash and cash equivalents
|
(94
|
)
|
(23
|
)
|
||||
Gain on adjustment of warrants to fair value
|
-
|
(465
|
)
|
|||||
Share-based compensation
|
472
|
916
|
||||||
Interest and exchange differences on short-term deposits
|
(143
|
)
|
(182
|
)
|
||||
Interest and linkage differences on bank loan
|
-
|
(1
|
)
|
|||||
351
|
386
|
|||||||
Changes in operating asset and liability items:
|
||||||||
Increase in prepaid expenses and other receivables
|
(802
|
)
|
(453
|
)
|
||||
Increase (decrease) in accounts payable and accruals
|
1,513
|
(542
|
)
|
|||||
711
|
(995
|
)
|
||||||
1,062
|
(609
|
)
|
||||||
Supplementary information on interest received in cash
|
137
|
167
|
a. |
General
|
b. |
Approval of financial statements
|
a. |
At-the-market (“ATM”) sales agreement with BTIG
|
b. |
Direct placement of share capital and warrants to BVF
|
Number of ordinary shares
|
||||||||
December 31,
|
March 31,
|
|||||||
2017
|
2018
|
|||||||
Authorized share capital
|
250,000,000
|
250,000,000
|
||||||
Issued and paid-up share capital
|
105,063,437
|
106,384,408
|
In USD and NIS
|
||||||||
December 31,
|
March 31,
|
|||||||
2017 |
2018
|
|||||||
Authorized share capital (in NIS)
|
25,000,000
|
25,000,000
|
||||||
Issued and paid-up share capital (in NIS)
|
10,506,344
|
10,638,441
|
||||||
Issued and paid-up share capital (in USD)
|
2,836,139
|
2,873,803
|
· |
the initiation, timing, progress and results of our preclinical studies, clinical trials and other therapeutic candidate development efforts;
|
· |
our ability to advance our therapeutic candidates into clinical trials or to successfully complete our preclinical studies or clinical trials;
|
· |
our receipt of regulatory approvals for our therapeutic candidates, and the timing of other regulatory filings and approvals;
|
· |
the clinical development, commercialization and market acceptance of our therapeutic candidates;
|
· |
our ability to establish and maintain corporate collaborations;
|
· |
our ability to integrate new therapeutic candidates and new personnel
|
· |
the interpretation of the properties and characteristics of our therapeutic candidates and of the results obtained with our therapeutic candidates in preclinical studies or clinical trials;
|
· |
the implementation of our business model and strategic plans for our business and therapeutic candidates;
|
· |
the scope of protection we are able to establish and maintain for intellectual property rights covering our therapeutic candidates and our ability to operate our business without infringing the intellectual property rights of others;
|
· |
estimates of our expenses, future revenues, capital requirements and our needs for additional financing;
|
· |
competitive companies, technologies and our industry; and
|
· |
the impact of the political and security situation in Israel on our business.
|
• |
BL-8040 is a novel, short peptide that functions as a high-affinity antagonist for CXCR4, which we are developing for the treatment of solid tumors, acute myeloid leukemia, or AML, and stem-cell mobilization for bone-marrow transplantation.
|
Ø
|
In January 2016, we entered into a collaboration with MSD in the field of cancer immunotherapy. Based on this collaboration, in September 2016 we initiated a Phase 2a study, known as the COMBAT study, focusing on evaluating the safety and efficacy of BL-8040 in combination with KEYTRUDA® (pembrolizumab), MSD’s anti-PD-1 therapy, in up to 30 patients with metastatic pancreatic adenocarcinoma. The study is an open-label, multicenter, single-arm trial designed to evaluate the clinical response, safety and tolerability of the combination of these therapies as well as multiple pharmacodynamic parameters, including the ability to improve infiltration of T cells into the tumor and their reactivity. Partial results from the monotherapy portion of this study show that BL-8040 increases infiltration of T cells into the tumor in patients with metastatic pancreatic cancer. Top-line results from the trial are expected in the second half of 2018.
|
Ø
|
In August 2016, in the framework of an agreement with MD Anderson Cancer Center, we entered into an additional collaboration for the investigation of BL-8040 in combination with KEYTRUDA in pancreatic cancer. The focus of this study, in addition to assessing clinical response, is the mechanism-of-action by which both drugs might synergize, as well as multiple assessments to evaluate the biological anti-tumor effects induced by the combination. We are supplying BL-8040 for this Phase 2b study, which commenced in January 2017.
|
Ø
|
In September 2016, we entered into a collaboration with Genentech, in the framework of which both companies would carry out Phase 1b/2 studies investigating BL-8040 in combination with TECENTRIQ® (atezolizumab), Genentech’s anti-PDL1 cancer immunotherapy, in various solid tumors and hematologic malignancies. Genentech commenced a Phase 1b/2 study for the treatment of pancreatic cancer in July 2017, as well as a Phase 1b/2 study in gastric cancer in October 2017. We anticipate that Genentech will commence an additional Phase 1b/2 study in lung cancer in 2018. These studies will evaluate the clinical response, safety and tolerability of the combination of these therapies, as well as multiple pharmacodynamic parameters.
|
Ø
|
During 2016, we completed and reported on a Phase 2a proof-of-concept trial for the treatment of relapsed or refractory acute myeloid leukemia, or r/r AML, which was conducted on 42 patients at six world-leading cancer research centers in the U.S. and at five premier sites in Israel. The study included both a dose-escalation and a dose-expansion phase. At the annual meetings of the Society of Hematologic Oncology and ASH in September and December 2016, respectively, we presented detailed, positive safety and response rate data for subjects treated with a combination of BL-8040 and high dose cytarabine, or HiDAC. In May 2018, we announced positive overall survival data from the long-term follow-up part of this study. We continue to monitor long-term survival data for patients in the study.
|
Ø
|
We are currently investigating BL-8040 as a consolidation treatment together with cytarabine (the current standard of care) for AML patients who have responded to standard induction treatment and are in complete remission and, in this regard, are conducting a significant Phase 2b trial in Germany, in collaboration with the German Study Alliance Leukemia Group. The Phase 2b trial is a double-blind, placebo-controlled, randomized, multi-center study aimed at assessing the efficacy of BL-8040 in addition to standard consolidation therapy in AML patients. Up to 194 patients will be enrolled in the trial. The primary endpoint of the study is to compare the relapse-free survival (RFS) time in AML subjects in their first remission during a minimum follow-up time of 18 months after randomization. We are considering conducting an interim analysis on this study in the second half of 2018, with top-line results expected in 2020.
|
Ø
|
In September 2017, we initiated a Phase 1b/2 trial in AML under the collaboration with Genentech referred to above in “― Solid tumors.” The trial will focus on the maintenance treatment of patients with intermediate- and high-risk AML who have achieved a complete response following induction and consolidation therapy. Up to 60 patients are planned to be enrolled in this single arm, open-label study, planned to take place at approximately 22 sites in the U.S., Europe and Israel.
|
Ø
|
In March 2015, we reported successful top-line safety and efficacy results from a Phase 1 safety and efficacy trial for the use of BL-8040 as a novel stem-cell mobilization treatment for allogeneic bone marrow transplantation at Hadassah Medical Center in Jerusalem.
|
Ø
|
In March 2016, we initiated a Phase 2 trial for BL-8040 for allogeneic stem-cell transplantation, conducted in collaboration with the Washington University School of Medicine, Division of Oncology and Hematology, or WUSM. Initial results of this study announced in March 2017 show that a single injection of BL-8040 mobilized sufficient amounts of cells required for transplantation at a level of efficacy similar to that achieved by using 4-6 injections of G-CSF, the current standard of care. In May 2018, we announced positive top-line results of this study.
|
Ø
|
In December 2017, we commenced a randomized, controlled Phase 3 registrational trial of BL-8040 for the mobilization of HSCs for autologous transplantation in patients with multiple myeloma. The trial will commence with a lead-in period for dose confirmation, which will include 10-30 patients, and progress to the placebo-controlled main part, which is designed to include 177 patients in more than 15 centers. Results from the lead-in period of the study are expected in mid-2018, and top-line results of placebo-controlled main part of the study are expected in 2020.
|
Ø
|
In addition to the above, we are currently conducting, or planning to conduct, a number of investigator-initiated, open-label studies in a variety of indications, to support the interest of the scientific and medical communities in exploring additional uses for BL-8040. These studies serve to further elucidate the mechanism of action for BL-8040.
|
Ø
|
In September 2013, the FDA granted an Orphan Drug Designation to BL-8040 as a therapeutic for the treatment of AML; and in January 2014, the FDA granted an Orphan Drug Designation to BL-8040 as a treatment for stem cell mobilization. In January 2015, the FDA modified this Orphan Drug Designation for BL-8040 for use either as a single agent or in combination with G-CSF.
|
• |
AGI-134, a near-clinical therapeutic candidate in-licensed by our subsidiary, Agalimmune Ltd., or Agalimmune, is a synthetic alpha-Gal glycolipid immunotherapy in development for solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant, anti-alpha-Gal antibodies to induce a hyper-acute, systemic, specific anti-tumor response to the patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on, anti-metastatic immune response. AGI-134 has completed numerous proof-of-concept studies, demonstrating robust protection against the development of secondary tumors in a model of melanoma with a single dose only. Synergy has also been demonstrated in the same model when combined with a PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies and improve the rate and duration of responses in multiple cancer types. A 28-day, repeated-administration GLP toxicology study in monkeys with AGI-134 has also been successfully completed. We expect to commence a first-in-man study using AGI-134 in patients with solid tumors in mid-2018.
|
• |
BL-5010 is a customized, proprietary pen-like applicator containing a novel, acidic, aqueous solution for the non-surgical removal of skin lesions. In December 2014, we entered into an exclusive out-licensing arrangement with a subsidiary of Perrigo Company plc, or Perrigo, for the rights to BL-5010 for over-the-counter, or OTC, indications in the territory of Europe, Australia and additional selected countries. In March 2016, Perrigo received CE Mark approval for BL-5010 as a novel OTC treatment for the non-surgical removal of warts. The commercial launch of this first OTC indication (warts/verrucas) commenced in Europe in the second quarter of 2016 and sales are expected to slowly ramp up over the next 2-3 years.
|
Project
|
Status
|
Expected Near Term Milestones
|
||
1. | Phase 2a study for relapsed or refractory AML completed | 1. | Follow-up for overall survival is ongoing | |
2. | Phase 2b consolidation treatment for AML ongoing | 2. | Possible interim results expected in H2 2018; top-line results expected in 2020 | |
3. | Phase 2 study in stem-cell mobilization ongoing | 3. | Top-line results expected in mid-2018 | |
4. | Phase 2a study in pancreatic cancer, in collaboration with Merck (COMBAT), ongoing; partial results presented at ASCO-GI in January 2018 | 4. | Top-line results expected in H2 2018 | |
BL-8040
|
5. | Phase 2b study in pancreatic cancer, in collaboration with MD Anderson Cancer Center, ongoing | 5. | Top-line results expected in H2 2018 |
6. | Phase 1b/2 study in AML, in collaboration with Genentech (BATTLE), commenced | 6. | Top-line results expected in 2019 | |
7. | Phase 1b/2 studies in pancreatic and gastric cancer, under collaboration with Genentech (MORPHEUS) commenced | 7. | Top-line results expected in 2019; commencement of additional study in lung cancer expected in 2018 | |
8. | Phase 3 registration study in autologous stem-cell mobilization commenced (GENESIS) | 8. | Partial results from initial lead-in, dose-confirmation part of the study expected mid-2018; top-line results from full study expected in 2020 | |
AGI-134
|
Near-clinical development studies
|
Commencement of first-in-man study expected in mid-2018
|
||
BL-5010
|
Out-licensed to Perrigo; CE mark approval obtained; commercial launch of first OTC indication in Europe commenced
|
Gradual full roll-out of commercial launch over next 2-3 years; pursuit of potential out-licensing partner(s) for OTC and non-OTC rights still held by us
|
|
||||||||||||||||||||
Year Ended December 31,
|
Three Months Ended March 31, 2018
|
Total Costs Since Project Inception
|
||||||||||||||||||
2015
|
2016
|
2017
|
||||||||||||||||||
(in thousands of U.S. dollars)
|
||||||||||||||||||||
BL-8040
|
7,045
|
8,281
|
12,369
|
2,957
|
39,983
|
|||||||||||||||
AGI-134
|
-
|
-
|
3,730
|
783
|
4,513
|
|||||||||||||||
BL-5010
|
400
|
75
|
32
|
14
|
4,190
|
|||||||||||||||
Other projects
|
3,573
|
2,647
|
2,628
|
863
|
117,622
|
|||||||||||||||
Total gross direct project costs
|
11,018
|
11,003
|
18,759
|
4,617
|
166,308
|
· |
the number of sites included in the clinical trials;
|
· |
the length of time required to enroll suitable patients;
|
· |
the number of patients that participate in the clinical trials;
|
· |
the duration of patient follow-up;
|
· |
whether the patients require hospitalization or can be treated on an out-patient basis;
|
· |
the development stage of the therapeutic candidate; and
|
· |
the efficacy and safety profile of the therapeutic candidate.
|
Three months ended March 31,
|
||||||||||||
2017
|
2018
|
Increase (decrease)
|
||||||||||
(in thousands of U.S. dollars)
|
||||||||||||
Research and development expenses
|
3,590
|
5,070
|
1,480
|
Three months ended March 31,
|
||||||||||||
2017
|
2018
|
Increase (decrease)
|
||||||||||
(in thousands of U.S. dollars)
|
||||||||||||
Sales and marketing expenses
|
681
|
484
|
(197
|
)
|
Three months ended March 31,
|
||||||||||||
2017
|
2018
|
Increase (decrease)
|
||||||||||
(in thousands of U.S. dollars)
|
||||||||||||
General and administrative expenses
|
1,030
|
1,075
|
45
|
Three months ended March 31,
|
||||||||||||
2017
|
2018
|
Increase (decrease)
|
||||||||||
(in thousands of U.S. dollars)
|
||||||||||||
Non-operating income (expenses), net
|
(5
|
)
|
462
|
467
|
Three months ended March 31,
|
||||||||||||
2017
|
2018
|
Increase (decrease)
|
||||||||||
(in thousands of U.S. dollars)
|
||||||||||||
Financial income
|
457
|
175
|
(282
|
)
|
||||||||
Financial expenses
|
(6
|
)
|
(206
|
)
|
(200
|
)
|
||||||
Net financial income (expenses)
|
451
|
(31
|
)
|
(482
|
)
|
· |
the progress and costs of our preclinical studies, clinical trials and other research and development activities;
|
· |
the scope, prioritization and number of our clinical trials and other research and development programs;
|
· |
the amount of revenues we receive under our collaboration or licensing arrangements;
|
· |
the costs of the development and expansion of our operational infrastructure;
|
· |
the costs and timing of obtaining regulatory approval of our therapeutic candidates;
|
· |
the ability of our collaborators to achieve development milestones, marketing approval and other events or developments under our collaboration agreements;
|
· |
the costs of filing, prosecuting, enforcing and defending patent claims and other intellectual property rights;
|
· |
the costs and timing of securing manufacturing arrangements for clinical or commercial production;
|
· |
the costs of establishing sales and marketing capabilities or contracting with third parties to provide these capabilities for us;
|
· |
the costs of acquiring or undertaking development and commercialization efforts for any future product candidates;
|
· |
the magnitude of our general and administrative expenses;
|
· |
any cost that we may incur under current and future licensing arrangements relating to our therapeutic candidates; and
|
· |
payments to the OCS.
|