On August 6, 2019 Leap Therapeutics, Inc. (NASDAQ:LPTX) reported that its anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with Merck’s anti-PD-1 antibody, KeytrudaÒ (pembrolizumab), demonstrated higher survival and objective response outcomes in patients with advanced gastroesophageal junction and gastric cancer (GEJ/GC) whose tumors expressed high levels of DKK1 (DKK1-high) (Press release, Leap Therapeutics, AUG 6, 2019, View Source [SID1234538168]). DKN-01 plus Keytruda therapy achieved over 22 weeks median progression-free survival (PFS) and nearly 32 weeks median overall survival (OS) with a 50% overall response rate (ORR) and 80% disease control rate (DCR) in patients with DKK1-high GEJ/GC who had not received prior anti-PD-1/PD-L1 therapy. Leap will host a DKN-01 Clinical Perspectives and Program Update for the investment community through a live conference call and webcast with two clinical investigators today at 8:30 AM US Eastern Time.

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"Gastric and gastroesophageal junction cancers represent a major global cancer burden with significant unmet needs, particularly in patients with advanced disease. Outside of rare microsatellite instable tumors and EBV-associated cancers the response rates to immune checkpoint inhibitors are low and median progression free survival remains short, in the range of 6-8 weeks. Oncologists and patients are eager for new therapeutic combinations and biomarkers to help predict patients most likely to benefit from a given treatment," stated Samuel J. Klempner, MD, Assistant Professor, Massachusetts General Hospital Cancer Center and Harvard Medical School.

"The responses and early survival data seen in DKK1-high patients treated with DKN-01 plus pembrolizumab are highly encouraging," commented Dr. Klempner. "This study builds on previously reported positive monotherapy and paclitaxel combination data and importantly suggests that elevated DKK-1 expression is a potential predictive biomarker. DKN-01 warrants further study in gastroesophageal cancers in combination with immune checkpoint inhibitors and with chemotherapy."

Key Findings from KEYNOTE-731 DKN-01 plus Keytruda Combination

The esophagogastric cancer clinical trial is a multipart study of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab. Sixty-three patients were treated with DKN-01 plus Keytruda combination therapy across all arms and dose groups of the study. Fifty-three patients had not received prior PD-1/PD-L1 therapy, and ten patients were refractory to PD-1/PD-L1 therapy. All of the patients enrolled had tumors that were microsatellite stable or unknown. Patients in the study were heavily pretreated having had received one to five prior lines of therapy, with nearly 64% having received a prior taxane regimen, 37% having received prior ramucirumab, and 24% having received prior trastuzumab. The combination therapy was well tolerated with no new safety signals.

The combination of DKN-01 and Keytruda in GEJ/GC patients demonstrated improved outcomes in patients whose tumors are DKK1-high and who were PD-1/PD-L1 naïve. DKK1-high patients experienced

over 22 weeks median PFS and nearly 32 weeks OS, with a 50% ORR and 80% DCR in ten evaluable patients. DKK1-low patients experienced nearly 6 weeks median PFS and over 17 weeks OS, with a 20% DCR in fifteen evaluable patients.

PD-L1 Combined Positive Scores (CPS) did not predict efficacy on the combination of DKN-01 plus Keytruda. In multi-variate analysis, DKK1-high status correlated with longer PFS independent of PD-L1 CPS scores. One-third of patients in the study were DKK1-high.

Among the six GEJ/GC patients who were refractory to PD-1/PD-L1 therapy, three DKK1-high patients had a best response of stable disease, whereas the three patients with DKK1-low tumors had progressive disease.

DKN-01 Clinical Perspectives Conference Call and Webcast

Samuel J. Klempner, MD, Assistant Professor, Massachusetts General Hospital Cancer Center and Harvard Medical School, will describe his experience with treating esophagogastric cancer patients in the DKN-01 study. In addition, Rebecca C. Arend, MD, Assistant Professor and Associate Scientist, Gynecologic Oncology Clinic, UAB Comprehensive Cancer Center Experimental Therapeutics Program, will discuss her experience with endometrial cancer and carcinosarcoma patients treated with DKN-01.

To access the conference call, please dial (866) 589-0108 (US/Canada Toll-Free) or (409) 231-2048 (international) and refer to conference ID 3571417. The presentation will also be webcast live and will be available under "Events & Presentations" in the Investor section of Leap’s website, View Source A replay of the webcast will be available on Leap’s website shortly after the event and will be available for a limited time.

On August 6, 2019 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology, reports its financial results for the quarter ended June 30, 2019 and provides a corporate update (Press release, BioLineRx, AUG 6, 2019, View Source [SID1234538198]).

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Highlights and achievements during the second quarter 2019 and subsequent period:

Continued to advance multiple clinical trials of its lead therapeutic candidates, BL-8040 and AGI-134, and anticipates top-line data from the triple combination arm of the COMBAT/KEYNOTE-202 pancreatic cancer trial by year-end.

Received approval from the FDA for an Investigational New Drug (IND) application for AGI-134, which will enable expansion of the ongoing Phase 1/2a study, currently being carried out in the UK and Israel, to the US by the first half of 2020.

"BL-8040, our lead drug candidate, is rapidly advancing in multiple promising programs. The triple combination arm of our ongoing COMBAT/KEYNOTE-202 Phase 2 study of BL-8040, KEYTRUDA and chemotherapy in metastatic pancreatic cancer is progressing as planned, and top-line results are expected by year end. AML consolidation also remains an important indication in our BL-8040 development plan, and we, with our partners, continue to progress our BLAST Phase 2b study towards a robust interim analysis. In addition, the GENESIS Phase 3 study in stem cell mobilization, our most advanced indication and most direct path to registration, is progressing as planned with top-line results expected in the second half of next year," stated Philip Serlin, Chief Executive Officer of BioLineRx.

"Regarding our second clinical candidate, the universal anti-cancer vaccine AGI-134, we continue to advance our phase 1/2a clinical trial toward initial safety data later this year, and with the acceptance of our IND, we look forward to the next part of the study, which will assess potential efficacy. Taken together, we believe our broad development pipeline provides multiple opportunities for long-term value creation and we are diligently working toward that goal," Mr. Serlin concluded.

Upcoming Milestones

Second half of 2019

Top-line results from COMBAT/KEYNOTE-202 Phase 2 pancreatic cancer trial

Initial safety results from part 1 of Phase 1/2a trial of AGI-134

Potential interim results from Phase 2b AML consolidation study

Initiation of monotherapy basket arm of Part 2 of Phase 1/2a trial of AGI-134

2020

Progression-free survival (PFS) and overall survival (OS) data from COMBAT/KEYNOTE-202 trial in mid-2020

Top-line results from Phase 3 GENESIS registration trial in stem-cell mobilization in second half of 2020

Financial Results for the Second Quarter Ended June 30, 2019

Research and development expenses for the three months ended June 30, 2019 were $5.3 million, an increase of $0.8 million, or 18%, compared to $4.5 million for the three months ended June 30, 2018. The increase resulted primarily from higher expenses associated with the BL-8040 GENESIS and COMBAT clinical trials. Research and development expenses for the six months ended June 30, 2019 were $9.7 million, an increase of $0.1 million, or 2%, compared to $9.6 million for the six months ended June 30, 2018. The small increase resulted primarily from higher expenses associated with the BL-8040 GENESIS and COMBAT clinical trials, offset by a decrease in expenses related to BL-1230, a project which was terminated, as well as a decrease in payroll and related expenses.

Sales and marketing expenses for the three months ended June 30, 2019 were $0.2 million, a decrease of $0.1 million, or 37%, compared to $0.3 million for the three months ended June 30, 2018. The decrease resulted primarily from a decrease in payroll and related expenses. Sales and marketing expenses for the six months ended June 30, 2019 were $0.5 million, a decrease of $0.4 million, or 43%, compared to $0.9 million for the six months ended June 30, 2018. The decrease resulted primarily from a decrease in payroll and related expenses, including a one-time compensation payment in the 2018 period.

General and administrative expenses for the three months ended June 30, 2019 were $0.9 million, similar to the comparable period in 2018. General and administrative expenses for the six months ended June 30, 2019 were $1.9 million, similar to the comparable period in 2018.

The Company’s operating loss for the three months ended June 30, 2019 was $6.5 million, compared to $5.7 million for the three months ended June 30, 2018. The Company’s operating loss for the six months ended June 30, 2019 was $12.1 million, compared to $12.4 million for the comparable period in 2018.

Non-operating income for the three and six months ended June 30, 2019 primarily relates to fair-value adjustments of warrant liabilities on the Company’s balance sheet, offset by warrant offering expenses. Non-operating income for the six months ended June 30, 2018 primarily relates to fair-value adjustments of warrant liabilities on the Company’s balance sheet, as well as a capital gain from realization of the investment in iPharma.

Net financial expenses amounted to $0.3 million for the three months ended June 30, 2019 compared to net financial income of $0.3 million for the three months ended June 30, 2018. Net financial expenses for the 2019 period primarily relate to interest paid on loans, offset by investment income earned on bank deposits. Net financial income for the 2018 period primarily relates to investment income earned on bank deposits, offset by losses recorded on foreign currency hedging transactions. Net financial expenses amounted to $0.5 million for the six months ended June 30, 2019 compared to net financial income of $0.3 million for the six months ended June 30, 2018. Net financial expenses for the 2019 period primarily relate to interest paid on loans, offset by investment income earned on bank deposits. Net financial income for the 2018 period primarily relates to investment income earned on bank deposits, offset by losses recorded on foreign currency hedging transactions.

The Company’s net loss for the three months ended June 30, 2019 amounted to $5.5 million, compared with a net loss of $4.8 million for the comparable period in 2018. The Company’s net loss for the six months ended June 30, 2019 amounted to $11.6 million, compared with a net loss of $11.0 million for the comparable period in 2018.

The Company held $35.2 million in cash, cash equivalents and short-term bank deposits as of June 30, 2019.

Net cash used in operating activities was $11.1 million for the six months ended June 30, 2019, compared with net cash used in operating activities of $13.0 million for the six months ended June 30, 2018. The $1.9 million decrease in net cash used in operating activities during the six-month period in 2019, compared to the six-month period in 2018, was primarily the result of changes in operating asset and liability items in the two periods., i.e., a decrease in prepaid expenses and other receivables in 2019 versus an increase in 2018, as well as a higher decrease in accounts payable and accruals in 2018.

Net cash used in investing activities was $3.1 million for the six months ended June 30, 2019, compared to net cash provided by investing activities of $10.8 million for the six months ended June 30, 2018. The changes in cash flows from investing activities relate primarily to investments in, and maturities of, short-term bank deposits and the realization of the investment in iPharma in 2018.

Net cash provided by financing activities was $15.7 million for the six months ended June 30, 2019, compared to net cash provided by financing activities of $2.8 million for the six months ended June 30, 2018. The increase in cash flows from financing activities reflects the underwritten public offering completed in February 2019.

Conference Call and Webcast Information

BioLineRx will hold a conference call today, August 6, 2019 at 10:00 a.m. EDT. To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0644 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 August 8, 2019; please dial +1-888-295-2634 from the U.S. or +972-3-925-5904 internationally.

On August 6, 2019 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company that engineers next-generation human enzymes to provide solutions for diseases with unmet medical need, reported financial results for the second quarter ended June 30, 2019 and corporate highlights (Press release, Aeglea BioTherapeutics, AUG 6, 2019, View Source [SID1234538214]).

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"We made tremendous progress this quarter with pegzilarginase, our lead product candidate for the treatment of Arginase 1 Deficiency (ARG1-D)," said Anthony G. Quinn, M.B. Ch.B., Ph.D., president and chief executive officer of Aeglea. "We dosed our first patient in our global pivotal Phase 3 PEACE trial, which is a major milestone toward providing our therapy to patients. The U.S. Food and Drug Administration’s (FDA) breakthrough therapy designation highlights the clinical relevance of the emerging data from the Phase 1/2 and Phase 2 open-label extension clinical trials as well as the potential of pegzilarginase to provide meaningful clinical improvements over available therapy."

Recent Highlights

Aeglea dosed the first patient in the Company’s global pivotal Phase 3 PEACE trial. The pivotal trial is intended to further evaluate the efficacy and safety of pegzilarginase, the Company’s lead product candidate for the treatment of ARG1-D, a progressive disease presenting in early childhood that results in severe complications and early mortality. The Company expects to report topline data from the PEACE trial in the first quarter of 2021.

The FDA granted Breakthrough Therapy Designation (BTD) to the Company’s lead product candidate, pegzilarginase, for the treatment of ARG1-D. The FDA’s BTD is intended to expedite the development and review of new therapies that are aimed at treating a serious or life-threatening condition when preliminary clinical evidence demonstrates the therapy may have substantial improvement on at least one clinically significant endpoint over available therapy. The designation was based on data from the completed Phase 1/2 clinical trial and the ongoing Phase 2 open-label extension study. Aeglea expects to continue discussions with the FDA regarding the pegzilarginase program and the Company’s next steps in the fourth quarter of 2019.

Interim data from 35 patients in the Company’s Phase 1/2 combination trial of pegzilarginase and KEYTRUDA in extensive disease small cell lung cancer revealed to date one complete response, four partial responses and 11 patients with stable disease. The combination trial was well tolerated, and safety observations were consistent with prior studies of pegzilarginase in patients with cancer. The Company has concluded enrollment and intends on submitting the results for presentation or publication after the final dataset becomes available.
Upcoming Events

Aeglea will present at the following conferences, with details regarding the date and time of the presentations and webcasts to be announced prior to the events.

Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium, September 3-6, Rotterdam, Netherlands
H.C. Wainwright & Co. 21st Annual Global Investment Conference, September 8-10, New York, NY
Second Quarter 2019 Financial Results

As of June 30, 2019, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $107.0 million. Based on Aeglea’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations through the first quarter of 2021.

Research and development expenses totaled $14.8 million for the second quarter of 2019, compared with $9.1 million for the second quarter of 2018. The increase was primarily due to expanded personnel-related expenses, clinical development activity, investment in manufacturing and pre-commercial activities for Aeglea’s lead product candidate, pegzilarginase, and a ramp-up in manufacturing activities for the Company’s AEB4104 program for homocystinuria.

General and administrative expenses totaled $3.8 million for the second quarter of 2019, compared with $2.9 million for the second quarter of 2018. This increase was primarily due to additional employee headcount and compensation to support company growth.

Net loss totaled $18.0 million and $9.4 million for the second quarter of 2019 and 2018, respectively, with non-cash stock compensation expense of $1.2 million and $1.0 million for the second quarter of 2019 and 2018, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is an enhanced human arginase that enzymatically depletes the amino acid arginine. Aeglea is developing pegzilarginase for the treatment of patients with Arginase 1 Deficiency, a rare debilitating disease presenting in childhood with persistent hyperargininemia, severe progressive neurological abnormalities and early mortality. Pegzilarginase is intended for use as an enzyme replacement therapy in patients to reduce elevated blood arginine levels. Aeglea’s Phase 1/2 and Phase 2 open-label extension data evaluating pegzilarginase in patients with Arginase 1 Deficiency demonstrated clinical improvements and sustained lowering of plasma arginine. Aeglea is currently recruiting patients for its single, global pivotal Phase 3 PEACE trial designed to assess the effects of treatment with pegzilarginase versus placebo over 24 weeks with a primary endpoint of plasma arginine reduction.

On August 6, 2019 Penumbra, Inc. (NYSE: PEN), a global healthcare company focused on innovative therapies, reported financial results for the second quarter ended June 30, 2019 (Press release, Penumbra, AUG 6, 2019, View Source [SID1234538230]).

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Revenue of $134.2 million in the second quarter of 2019, an increase of 22.4%, or 23.8% in constant currency1, over the second quarter of 2018.
Second Quarter 2019 Financial Results
Total revenue grew to $134.2 million for the second quarter of 2019 compared to $109.6 million for the second quarter of 2018, an increase of 22.4%, or 23.8% on a constant currency basis. The United States represented 64% of total revenue and international represented 36% of total revenue for the second quarter of 2019. Revenue from sales of neuro products grew to $81.5 million for the second quarter of 2019, an increase of 9.9%, or 11.5% on a constant currency basis. Revenue from sales of vascular products grew to $52.7 million for the second quarter of 2019, an increase of 48.6%, or 49.5% on a constant currency basis.

Gross profit was $93.9 million, or 70.0% of total revenue, for the second quarter of 2019, compared to $72.3 million, or 65.9% of total revenue, for the second quarter of 2018.

Total operating expenses for the second quarter of 2019 were $81.1 million, or 60.5% of total revenue. This compares to total operating expenses of $63.0 million, or 57.4% of total revenue, for the second quarter of 2018. R&D expenses were $13.5 million for the second quarter of 2019, compared to $8.2 million for the second quarter of 2018. SG&A expenses were $67.7 million for the second quarter of 2019, compared to $54.8 million for the second quarter of 2018.

Operating income for the second quarter of 2019 was $12.8 million, compared to operating income of $9.3 million for the second quarter of 2018.

Full Year 2019 Financial Outlook
The Company is increasing its 2019 guidance for total revenue to be in the range of $535 million to $540 million. This new range compares to the previous range of $525 million to $535 million.

Webcast and Conference Call Information
Penumbra, Inc. will host a conference call to discuss the second quarter 2019 financial results after market close on Tuesday, August 6, 2019 at 4:30 PM Eastern Time. The conference call can be accessed live over the phone by dialing (866) 393-4306 for domestic callers or (734) 385-2616 for international callers (conference id: 9790865), or the webcast can be accessed on the "Events" section under the "Investors" tab of the Company’s website at: www.penumbrainc.com. The webcast will be available on the Company’s website for at least two weeks following the completion of the call.

On August 6, 2019 Replimune Group, Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported that Philip Astley-Sparke, Executive Chairman and Director of Replimune, will present and host one-on-one meetings at the 2019 Wedbush PacGrow Healthcare Conference being held in New York City (Press release, Replimune, AUG 6, 2019, View Source [SID1234538170]). The Company is scheduled to present on Wednesday, August 13, 2019 at 1:55 PM ET.

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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

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