On December 13, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, will present updated interim results from a Phase II clinical trial of Puma’s drug neratinib at the 2019 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 13, 2019, View Source [SID1234552359]). The presentation entitled, "Effect of prophylaxis or neratinib dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2-positive early-stage breast cancer: Phase II CONTROL trial," will be displayed at a poster session on December 13 at 5:00 p.m. CST. A full copy of the poster is available on the Puma Biotechnology website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed in the United States as NERLYNX (neratinib) tablets.

The main adverse event seen to date in clinical trials of neratinib is diarrhea and, more specifically, grade 3 diarrhea. In the Phase III ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with adjuvant Herceptin, prophylactic use of anti-diarrheal medications was not mandatory. In the trial, 95.4% of the patients experienced all grade diarrhea and 39.8% of the patients experienced grade 3 or higher diarrhea (there was one event of grade 4 diarrhea). The median cumulative duration of grade 3 diarrhea in the ExteNET trial was 5 days and 16.8% of patients who received neratinib in the ExteNET trial discontinued the drug due to diarrhea.

The CONTROL trial is an international, open-label, Phase II study investigating the use of antidiarrheal prophylaxis or dose escalation in the reduction of neratinib-associated diarrhea that has a primary endpoint of the incidence of grade 3 diarrhea.

In the CONTROL trial, patients with HER2-positive early stage breast cancer who had completed trastuzumab-based adjuvant therapy received neratinib daily for a period of one year. The trial initially tested high dose loperamide prophylaxis given for the first 2 cycles (56 days) of treatment (12 mg on days 1-14, 8 mg on days 15-56 and as needed thereafter). The CONTROL trial was then expanded to include four additional cohorts. One cohort received the combination of loperamide and budesonide, the second cohort received the combination of loperamide plus colestipol, the third cohort received colestipol plus loperamide as needed and the fourth cohort did not use any antidiarrheal drugs as mandatory prophylaxis but instead used a dose escalation during the first month of neratinib treatment. Budesonide is a locally acting corticosteroid that Puma believes targets the inflammation identified in a preclinical model of neratinib-induced diarrhea and colestipol is a bile acid sequestrant that Puma believes targets potential bile acid malabsorption that could result from such inflammation. The dose escalation involved treating with neratinib at 120 mg per day for the first week, 160 mg per week for the second week and 240 mg per week starting at week 3 and until the end of treatment.

The interim analysis of the CONTROL trial presented in the poster included a total of 137 patients who received neratinib plus loperamide prophylaxis, 64 patients who received neratinib plus loperamide prophylaxis for 2 cycles and budesonide for 1 cycle, 136 patients who received neratinib plus loperamide prophylaxis for 1 cycle and colestipol for 1 cycle, 104 patients who received colestipol for 1 cycle and loperamide as needed and 60 patients who received the dose escalation regimen of neratinib.

The results of the trial showed that the incidence of grade 3 diarrhea for the 137 patients who received the loperamide prophylaxis was 31% and that for the 137 patients in this cohort, 20% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 64 patients who received the combination of loperamide plus budesonide, the results of the trial showed that the incidence of grade 3 diarrhea was 28% and that for the 64 patients in this cohort, 11% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2.5 days.

For the 136 patients who received the combination of loperamide plus colestipol, the results of the trial showed that the incidence of grade 3 diarrhea was 21% and that for the 136 patients in this cohort, 4% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3.5 days.

For the 104 patients who received colestipol and loperamide as needed, the results of the trial showed that the incidence of grade 3 diarrhea was 34% and that for the 104 patients in this cohort, 8% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 3 days.

For the 60 patients who received no antidiarrheal drugs as mandatory prophylaxis and dose escalation of neratinib in the first month, the results of the trial showed that the incidence of grade 3 diarrhea was 15% and that for the 60 patients in this cohort, 3% discontinued neratinib due to diarrhea. The median cumulative duration of grade 3 diarrhea was 2 days.

Further information is provided in Table 1 below:

Each patient was counted only once in the highest grade category.

No Grade 4 events reported in the CONTROL study.

Carlos H. Barcenas, MD, MS, Associate Professor in the Department of Breast Medical Oncology of The University of Texas MD Anderson Cancer Center, said, "We are pleased to see the maturation of the data supporting observations of a reduction in incidence, severity and duration of neratinib-associated diarrhea with loperamide prophylaxis, loperamide plus budesonide prophylaxis or the loperamide plus colestipol prophylaxis. Along with the continued reduction in the incidence and severity of grade 3 diarrhea with neratinib, diarrhea appears to be early onset, acute, self-limiting and manageable. Not only does the addition of budesonide or colestipol to loperamide prophylaxis appear to greatly improve the tolerability of neratinib, the dose escalation regimen appears as another promising option since there is no mandatory prophylaxis."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased to note that the dose-escalation cohort of our CONTROL trial continues to show a marked improvement in the incidence of grade 3 diarrhea and related discontinuation of therapy. We remain committed to improving the tolerability of neratinib in early stage breast cancer patients."

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

IMPORTANT SAFETY INFORMATION

NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. When patients require gastric acid reducing agents, use an H2-receptor antagonist or antacid. Separate NERLYNX by at least 3 hours with antacids. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

On December 13, 2019 Susan G. Komen, the world’s leading breast cancer organization, reported the results of the INFORM trial that were announced at the 2019 San Antonio Breast Cancer Symposium (Press release, Susan G Komen, DEC 13, 2019, View Source [SID1234552378]). The Komen-funded INFORM trial led by Dr. Nadine Tung shows that HER2-negative patients with a BRCA1/2 gene mutation have multiple effective treatment options.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Tung and colleagues sought to determine if cisplatin chemotherapy is a more effective treatment than the current, standard of care treatment, chemotherapy with doxorubicin and cyclophosphamide (commonly referred to as "AC"). Prior retrospective studies, which looked at treatment that has already occurred as part of the study, had indicated that cisplatin chemotherapy might work better than AC. The INFORM clinical trial was the first prospective study, or a study that evaluates treatment moving forward, to actually test this idea.

"For HER2-negative breast cancer patients with BRCA1/2 mutations, the INFORM trial confirmed that cisplatin chemotherapy is not more effective than standard chemotherapy with doxorubicin and cyclophosphamide. The results suggest that BRCA carriers may respond to both types of chemotherapy – which kill cancer cells by damaging DNA – giving them multiple options to treat their cancer," said Dr. Tung. Prospective studies are essential for improving clinical practice.

She added, "Funding from Susan G. Komen was essential for this work." Funded in part by a Komen Opportunity Grant, the INFORM trial is also part of the Translational Breast Cancer Research Consortium (TBCRC), which has been supported by Komen for more than 10 years.

Victoria Wolodzko, senior vice president of Mission at Susan G. Komen, added, "Patients with BRCA mutations face many challenges, especially those in rural or underserved areas. This work confirms that physicians have more options for these patients. Patients won’t need to wait for a specific treatment to ensure they are getting the best care no matter where they live."

On December 13, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the Phase III IMspire150 study, in people with previously untreated BRAF V600 mutation-positive advanced melanoma, met its primary endpoint of progression-free survival (PFS) (Press release, Hoffmann-La Roche, DEC 13, 2019, View Source [SID1234552341]). The study showed adding Tecentriq (atezolizumab) to Cotellic (cobimetinib) and Zelboraf (vemurafenib) helped to reduce the risk of disease worsening or death, compared to placebo plus Cotellic and Zelboraf.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A significant and clinically meaningful improvement in PFS was demonstrated in the study. The safety profile observed in IMspire150 was consistent with the known safety profiles of the individual medicines. Results from the study will be presented at an upcoming medical meeting and discussed with health authorities, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

"By combining a cancer immunotherapy with targeted therapies, we hope to offer a new approach that improves outcomes for people with advanced, BRAF-mutant melanoma." said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "We look forward to discussing the results with health authorities around the world."

Roche has an extensive clinical trial development programme for Tecentriq, with more than 50 ongoing studies, including multiple Phase III studies across lung, kidney, skin, breast, colorectal, prostate, ovarian, bladder, blood, liver and head and neck cancers. Studies are evaluating Tecentriq alone and in combination with other medicines.

About the IMspire150 study
IMspire150 is a Phase III, multi-centre, double-blind, placebo-controlled randomised study in people with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma. The study compared the efficacy and safety of Tecentriq plus Cotellic and Zelboraf to the combination of placebo plus Cotellic and Zelboraf. The primary endpoint of the study was investigator-assessed PFS. Key secondary endpoints include PFS by an independent review committee, overall survival, objective response rate, duration of response and other safety and pharmacokinetic measures.

About advanced melanoma
Melanoma is a less common, but more aggressive and potentially deadly form of skin cancer.1,2,3 When melanoma is diagnosed early, it is generally a curable disease,4,5 but most people with advanced melanoma have a poor prognosis.2 More than 287,000 people worldwide are currently diagnosed with melanoma each year.6 In recent years, there have been significant advances in treatment for advanced melanoma and people with the disease have more options. However, it continues to be a serious health issue with a high medical need and a steadily increasing incidence over the past 30 years.7

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Cotellic (cobimetinib)
Cotellic is designed to inhibit MEK1/2, proteins in a cell signalling pathway that helps control cell growth and survival. Cotellic, when used in combination with Zelboraf, is approved in the United States and Europe, as well as many countries around the world, for the treatment of people with melanoma that has spread to other parts of the body or cannot be removed by surgery and has a BRAF V600 mutation. Cotellic was discovered by Exelixis and is being developed by Genentech, a member of the Roche Group, in collaboration with Exelixis.

About Zelboraf (vemurafenib)
Zelboraf is a prescription medicine for the treatment of people with melanoma that has spread to other parts of the body or cannot be removed by surgery and has BRAF V600 mutation. Zelboraf is designed to inhibit some mutated forms of BRAF, which cause abnormal signalling inside cancer cells leading to tumour growth. BRAF is a protein in a cell signalling pathway that helps control cell growth and survival. Zelboraf was the first approved product in its class. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon Inc., the small molecule structure-guided R&D centre of the Daiichi Sankyo Group.

On December 13, 2019, Sarepta Therapeutics, Inc. (the "Company") reported that it entered into a loan agreement (the "Credit Agreement") with BioPharma Credit PLC, a public limited liability company incorporated under the laws of England and Wales, as the collateral agent and a lender ("BioPharma"), and BioPharma Credit Investments V (Master) LP, a Cayman Islands exempted limited partnership, as a lender (together with BioPharma in its capacity as a lender, and each of their respective successors and assigns at any time party to the Credit Agreement, the "Lenders" and each a "Lender") that provides for a senior secured term loan facility of up to $500.0 million to be funded in two tranches: (i) a Tranche A Loan in an aggregate principal amount of $250.0 million (the "Tranche A Loan") to be funded on or about December 20, 2019 (the "Tranche A Funding Date"), subject to entering into a security agreement (the "Security Agreement") and delivery of other customary deliverables; and (ii) a Tranche B Loan in an aggregate principal amount of up to $250.0 million (the "Tranche B Loan", and together with the Tranche A Loan, the "Term Loans"), to be funded at the option of the Company, and at the Company’s option, in increments of $50.0 million and no later than December 31, 2020, and in any event upon no less than 75 days’ notice (unless the Lenders agree to a shorter notice period) (Filing, 8-K, Sarepta Therapeutics, DEC 13, 2019, View Source [SID1234552360]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Term Loans mature on the 48th-month anniversary of the Tranche A Funding Date (the "Maturity Date"). Borrowings under the Credit Agreement bear interest at a fixed rate equal to 8.50% per annum payable quarterly in arrears. 50.0% of the interest on the Tranche A Loan payable during the first twelve (12) months following the Tranche A Funding Date may be paid-in-kind at the election of the Company. All unpaid principal (including accrued and capitalized paid-in-kind interest) with respect to the Term Loans is due and payable on the Maturity Date.

The Company will pay to each Lender a funding fee equal to 1.75% on the funded amount of the Term Loans, payable when each Term Loan is funded. At the time of prepayment or repayment of any amount of the Term Loans, the Company will pay to each Lender a fee equal to 2.00% of the Term Loans held by such Lender being prepaid or repaid. In addition, in the event a tranche is prepaid in whole or in part prior to the Maturity Date, it will be subject to a prepayment fee. On or prior to the third anniversary of the applicable funding date, the prepayment fee is 2.00% of the principal amount prepaid, thereafter and prior to the Maturity Date, the prepayment fee is 1.00% of the principal amount prepaid. In addition to the prepayment fees, in connection with a full or partial prepayment of a tranche prior to the second anniversary of the applicable funding, a "make-whole" amount will be payable equal to the foregone interest from the date of prepayment through the second anniversary.

All obligations under the Credit Agreement as of the Tranche A Funding Date will be secured, subject to certain exceptions, by security interests in (collectively, the "Collateral"): (1) U.S. intellectual property owned by, and rights to U.S. intellectual property licensed to, the Company relating to any pharmaceutical composition in which eteplirsen or golodirsen is indicated to be administered for use in the treatment of Duchenne muscular dystrophy ("DMD") in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 or 53 skipping, respectively, or for any other use approved by the FDA (the "Products"), (2) 100% of the equity interests directly held by the Company in certain wholly owned domestic subsidiaries and 65% of the equity interests in certain other wholly owned domestic subsidiary, and (3) all of the Company’s personal property, including, without limitation, cash held in all deposit accounts of the Company. Any non-U.S. intellectual property related to the Products and intellectual property unrelated in any way to the Products anywhere are not part of the Collateral.

The Credit Agreement contains negative covenants that, among other things and subject to certain exceptions, restrict the Company’s ability to:

sell or dispose of assets, including certain intellectual property;

amend, modify or waive certain material agreements or organizational documents;

consolidate or merge;

incur additional indebtedness;

incur additional liens on the Collateral;

pay dividends or make any distribution or payment on or redeem, retire or purchase any equity interests; and

make payments of certain subordinated indebtedness.

The Credit Agreement requires the Company to have consolidated liquidity of at least $100,000,000 as of the last day of each month. Additionally, the Credit Agreement contains certain customary representations and warranties, affirmative covenants and provisions relating to events of default, including nonpayment of principal, interest and other amounts; failure to comply with covenants; the occurrence of a material adverse change in (i) the ability of the Company to fulfill the payment or performance obligations under the Credit Agreement and related documents or (ii) the binding nature of the Credit Agreement and related documents; the rendering of judgments or orders or the acceleration or payment default by the Company in respect of other indebtedness in excess of $10 million; and certain insolvency and ERISA events. A change of control of the Company triggers a mandatory prepayment of the Term Loans.

On December 13, 2019 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology, reported updated data from the triple combination arm of the ongoing Phase 2a COMBAT/KEYNOTE-202 study (Press release, BioLineRx, DEC 13, 2019, View Source [SID1234552344]). The data was delivered today in an oral presentation entitled, "A Multi-Center Phase 2a Trial to Assess the Safety and Efficacy of BL-8040 (a CXCR4 inhibitor) in Combination with Pembrolizumab and Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC)", at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress (ESMO IO) 2019, which is being held December 11-14 in Geneva, Switzerland. The full presentation is available on the Company’s website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Updated Data from the Triple Combo Arm of the COMBAT/KEYNOTE-202 Study
As of today’s date, 36 out of 40 patients have been enrolled in the study. As of December 5, 2019 (the cutoff date for the presentation data), 30 patients were evaluable for safety and 22 were evaluable for efficacy. All patients enrolled were originally diagnosed with stage IV metastatic pancreatic adenocarcinoma (PDAC) and had progressed following first-line treatment with gemcitabine-based chemotherapy.

Best response for the evaluable population of 22 patients showed 7 partial response (PR) and 10 stable disease (SD) patients – resulting in an overall response rate (ORR) of 32% and a disease control rate (DCR) of 77%; this compares favorably to the current chemotherapy standard-of-care treatment (Onivyde/5-fluorouracil/leucovorin) in second-line patients with ORR of 17% and DCR of 52%;

The combination showed continuity of effect – 5 patients with stable disease became partial responders as treatment continued;

Out of the 7 partial responders, 5 are still on treatment, with a current maximum treatment time of 330+ days; and 4 responders showed a reduction in tumor burden of >50%;

Median duration of clinical benefit until progression for the 17 patients with disease control (7 PR and 10 SD patients) is 7.8 months;

The study is ongoing; progression-free and overall survival data remain on track for mid-2020;

The combination was generally well tolerated, with a safety profile consistent with the individual safety profile of each component alone; adverse event (AE) and severe adverse event (SAE) profiles are as expected with chemotherapy-based treatment regimens.

"Metastatic pancreatic cancer has a very poor response to chemotherapy, and immunotherapy treatments have failed to show any effect as single agents," said Manuel Hidalgo, MD, PhD, Chief of the Division of Hematology and Medical Oncology and a Senior Member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center, and principal investigator of this study. "These promising initial results presented today show an overall response rate double the current chemotherapy standard-of-care treatment in second-line patients. The results are even stronger when taking into account the extended durability of clinical benefit seen to date in this study (median of 7.8 months), compared to approximately three months of response duration with other treatments for second-line pancreatic cancer. I look forward to the survival data expected in mid-2020."

"We are very excited by the positive data accumulating from this triple combination arm of our Phase 2a pancreatic study under our collaboration with Merck," stated Philip Serlin, Chief Executive Officer of BioLineRx. "These data continue to confirm our hypothesis relating to the synergistic effect of cytotoxic chemotherapy, along with the trafficking, tumor microenvironment modulation and T-cell infiltration effects seen in PDAC patients from previous dual combination trials of BL-8040 with checkpoint inhibitors. It is therefore very encouraging to see robust and durable responses to the triple combination treatment, especially as we continue to see a trend of patients receiving treatment for an extended period that move from stable disease to partial response. We hope to see these results translate into an extended survival benefit for these patients, which we expect to announce in mid-2020, and we hope will pave the way for use of immunotherapy in pancreatic cancer and in other cold tumors."

Design of Triple Combination Arm of COMBAT/KEYNOTE-202 Study
The triple combination arm focuses on second-line pancreatic cancer patients and is expected to include approximately 40 patients originally diagnosed with unresectable metastatic pancreatic adenocarcinoma who have progressed following first-line gemcitabine-based therapy. Patients receive BL-8040 monotherapy priming treatment for five days, followed by combination cycles of chemotherapy (Onivyde/5-fluorouracil/leucovorin), KEYTRUDA and BL-8040 until progression. The primary endpoint of the study is the objective response rate (ORR). Secondary endpoints include overall survival, progression free survival, and disease control rate.

The COMBAT/KEYNOTE-202 Study
The Phase 2a COMBAT/KEYNOTE-202 study was originally designed as an open-label, multicenter, single-arm trial to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in over 30 subjects with metastatic pancreatic adenocarcinoma. The study was primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies, and was carried out in the US, Israel and additional territories. The study is being conducted by BioLineRx under a collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary.

In July 2018, the Company announced the expansion of its immuno-oncology collaboration with MSD to include the triple combination arm investigating the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy as part of the Phase 2a COMBAT/KEYNOTE-202 study.

About BL-8040 in Cancer Immunotherapy
BL-8040 is targeting CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis.

BL-8040 is a short synthetic peptide used as a platform for cancer immunotherapy with unique features allowing it to function as a best-in-class antagonist of CXCR4. It shows high-affinity, long receptor occupancy and acts as an inverse agonist.

In a number of clinical and preclinical studies, BL-8040 has been shown to affect multiple modes of action in "cold" tumors, including immune cell trafficking, tumor infiltration by immune effector T cells, and reduction in immunosuppressive cells (such as MDSCs) within the tumor niche, turning "cold" tumors, such as pancreatic cancer, into "hot" (i.e., sensitizing them to immune checkpoint inhibitors and chemotherapy).

Conference Call and Webcast Information
BioLineRx will hold a conference call today, December 13, 2019 at 8:30 a.m. EST. To access the conference call, please dial +1-888-668-9141 from the U.S. or +972-3-918-0609 internationally. The call will also be available via webcast and can be accessed through the Investor Relations page of BioLineRx’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast.

A replay of the conference call will be available approximately two hours after completion of the live conference call on the Investor Relations page of BioLineRx’s website. A dial-in replay of the call will be available until December 15, 2019; please dial +1-888-782-4291 from the U.S. or +972-3-925-5927 internationally.