Approval of UCART123 Amendment in AML to Accelerate Clinical Development

On May 22, 2018 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported the approval of an amendment to the protocol for the Phase 1 clinical trial of Cellectis’ UCART123 product candidate in patients with acute myeloid leukemia (AML) (Press release, Cellectis, MAY 22, 2018, file:///C:/Users/LENOVO/Downloads/20180522_PR_UCART123_Protocol_Amendment_addendum%20(1).pdf [SID1234526851]).

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The main changes to the protocol include:

Dose level 1 to be administered increases from 6.25×104 to 2.5×105 UCART123 cells per kilogram. Dose levels 2 and 3 are now respectively at 6.25×105 and 5.05×106. Dose level -1 is now at 1.25×105. The product’s safety and tolerability profile allowed Cellectis to increase dose levels with a capping at 80kg equivalent.
The dose limiting toxicities (DLT) observation period decreases from 42 to 28 days post-UCART123 infusion, except for patients with aplastic bone marrow at Day 28 for whom the DLT observation period remains 42 days.
The time interval between the first and the second patient for UCART123 infusion at each new dose level tested shortens from 42 days to 28 days (42 days in case of aplastic anemia) then to 14 days for subsequent patients.
A potential second UCART123 infusion is implemented.
In addition, a new AML clinical center has been opened at MD Anderson Cancer Center in Houston, Texas, aiming at increasing the patient enrollment pace. The study is led by Prof. Hagop Kantarjian, MD, Department Chair, Department of Leukemia, Division of Cancer Medicine, and Dr. Naveen Pemmaraju, MD, Assistant Professor, being Principal Investigator.

"This amendment approval for Cellectis’ UCART123 protocol is an important step in the progression of our study, and opening another clinical site at MD Anderson – one of the world’s most premier cancer centers – puts the Company on solid ground to help as many AML patients as possible with this innovative new therapy," said Prof. Stéphane Depil, Senior Vice President, R&D, and Chief Medical Officer at Cellectis. "Off-the-shelf gene editing immunotherapy is continuing to revolutionize the landscape of modern medicine, and we hope that this approach leads to a lifesaving treatment for AML patients in the near future."

"As Cellectis has been working very closely with the concerned parties to review the details of UCART123 study to date, we are eager to hit the ground running with the new protocol in an effort to find a truly effective treatment for AML patients with high unmet medical needs," added Stéphan Reynier, Chief Regulatory and Compliance Officer at Cellectis. "We look forward to obtaining additional data so that we can address such a rare and devastating disease."

The FDA review period for this protocol amendment has passed and Cellectis obtained IRB’s approval.

More information about this trial is available at ClinicalTrials.gov.

About UCART123 clinical trial

Our first wholly controlled product candidate, UCART123, is a gene edited T-cell investigational drug that targets CD123, an antigen expressed at the surface of leukemic cells in AML. Cellectis received in February 2017 an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) to conduct Phase 1 clinical trial with UCART123 in patients with AML. This marks the first allogeneic, "off-the-shelf" gene-edited CAR T-cell product candidate that the FDA has approved for clinical trial.

UCART123 clinical trial in AML is a Phase 1, open label dose-escalation and dose-expansion study to evaluate the safety, expansion, persistence and clinical activity of UCART123 (allogeneic engineered T-cells expressing anti-CD123 chimeric antigen receptor), administered in patients with relapsed/refractory AML, and patients with newly diagnosed high-risk AML.

The clinical research is coordinated by principal investigator Prof. Gail J. Roboz, MD, at Weill Cornell, Professor of Medicine at Weill Cornell Medicine and Director of the Clinical and Translational Leukemia Programs at Weill Cornell Medicine and NewYork-Presbyterian.

AML is a devastating clonal hematopoietic stem cell neoplasm that is characterized by uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues. These cells disrupt normal hematopoiesis and rapidly cause bone marrow failure and death. In the U.S. alone, there are in 2017 an estimated 21,000 new AML cases per year, with 10,000 estimated deaths per year

About UCART123 clinical trial
Our first wholly controlled product candidate, UCART123, is a gene edited T-cell investigational drug that targets CD123, an antigen expressed at the surface of leukemic cells in AML. Cellectis received in February 2017 an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) to conduct Phase 1 clinical trial with UCART123 in patients with AML. This marks the first allogeneic, "off-the-shelf"
gene-edited CAR T-cell product candidate that the FDA has approved for clinical trial.

UCART123 clinical trial in AML is a Phase 1, open label dose-escalation and doseexpansion study to evaluate the safety, expansion, persistence and clinical activity of UCART123 (allogeneic engineered T-cells expressing anti-CD123 chimeric antigen receptor), administered in patients with relapsed/refractory AML, and patients with newly
diagnosed high-risk AML.

The clinical research is coordinated by principal investigator Prof. Gail J. Roboz, MD, at Weill Cornell, Professor of Medicine at Weill Cornell Medicine and Director of the Clinical and Translational Leukemia Programs at Weill Cornell Medicine and NewYorkPresbyterian.

AML is a devastating clonal hematopoietic stem cell neoplasm that is characterized by uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues. These cells disrupt normal hematopoiesis and rapidly cause bone marrow failure and death. In the U.S. alone, there
are in 2017 an estimated 21,000 new AML cases per year, with 10,000 estimated deaths per year.

BioLineRx Reports First Quarter 2018 Financial Results

On May 22, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported its financial results for the first quarter ended March 31, 2018 (Press release, BioLineRx, MAY 22, 2018, View Source;p=RssLanding&cat=news&id=2350176 [SID1234526848]).

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Highlights and achievements during the first quarter 2018 and to date:

Steady progress made on multiple clinical trials for the Company’s lead oncology program, BL-8040:

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.
The Company also announced advancements made in its second immuno-oncology compound, AGI-134:

Pre-clinical data presented at ASCO (Free ASCO Whitepaper)-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.
Expected significant upcoming milestones for 2018:

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 (Free EHA Whitepaper) 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) (Free EHA Whitepaper) in June 2018.

Philip A. Serlin, Chief Executive Officer of BioLineRx, stated, "We continue to strongly focus on clinical execution of our oncology programs. Since the beginning of 2018, we have made significant progress with BL-8040, our lead clinical asset, with clinical results from our Phase 2a COMBAT study in pancreatic cancer showing robust mobilization and increased infiltration of anti-tumor-specific T cells into the tumor microenvironment; positive results from our Phase 2 study in allogeneic bone marrow transplantation; very encouraging overall survival data from our proof-of-concept Phase 2a study in relapsed/refractory AML; as well as significant strengthening of our patent protection for BL-8040 in the AML space. In addition, we also reported very encouraging pre-clinical data on our near-clinical second oncology asset, AGI-134, demonstrating induced regression of primary tumors following intra-tumoral injection.

"Over the next three to nine months, we look forward to reporting on key milestones. This includes the results from the lead-in part of our Phase 3 GENESIS trial in autologous stem cell mobilization, data read-outs from our Phase 2a COMBAT study in pancreatic cancer, and initiation of a Phase 1/2a study in multiple solid tumor indications for AGI-134," concluded Mr. Serlin.

Financial Results for the First Quarter Ended March 31, 2018

Research and development expenses for the three months ended March 31, 2018 were $5.1 million, an increase of $1.5 million, or 41.2%, compared to $3.6 million for the three months ended March 31, 2017. The increase resulted primarily from higher expenses associated with new BL-8040 clinical studies commenced during 2017, spending on our new AGI-134 near-clinical project, and higher expenses related to our BL-1230 project.

Sales and marketing expenses for the three months ended March 31, 2018 were $0.5 million, a decrease of $0.2 million, or 28.9%, compared to $0.7 million for the three months ended March 31, 2017. The decrease resulted primarily from one-time legal fees related to AGI-134 incurred in the 2017 period.

General and administrative expenses for the three months ended March 31, 2018 were $1.1 million, similar to the comparable period in 2017.

The Company’s operating loss for the quarter ended March 31, 2018 amounted to $6.6 million, compared with an operating loss of $5.3 million for the quarter ended March 31, 2017.

Non-operating income (expenses) for both periods primarily relate to fair-value adjustments of warrant liabilities. These fair-value adjustments were highly influenced by the Company’s share price at each period end (revaluation date).

The Company recorded an immaterial amount of net financial expenses for the three months ended March 31, 2018 compared to net financial income of $0.5 million for the three months ended March 31, 2017. Net financial expenses for the 2018 period primarily relate to investment income earned on bank deposits, offset by losses recorded on foreign currency hedging transactions. Net financial income for the 2017 period relates primarily to gains recorded on foreign currency hedging transactions and investment income earned on bank deposits.

The Company’s net loss for the three months ended March 31, 2018 amounted to $6.2 million, compared with a net loss of $4.9 million for the corresponding period.

The Company held $44.2 million in cash, cash equivalents and short-term bank deposits as of March 31, 2018.

Net cash used in operating activities was $6.8 million for the three months ended March 31, 2018, compared with net cash used in operating activities of $3.8 million for the three months ended March 31, 2017. The $3.0 million increase in net cash used in operating activities during the three-month period in 2018, compared to the three-month period in 2017, was the result of increased research and development expenses in the 2018 period, as well as a decrease in accounts payable.

Net cash provided by investing activities was $8.1 million for the three months ended March 31, 2018, compared to net cash provided by investing activities of $1.4 million for the three months ended March 31, 2017. The changes in cash flows from investing activities relate primarily to investments in, and maturities of, short-term bank deposits, as well as the investment in Agalimmune in 2017 period.

Net cash provided by financing activities was $1.4 million for the three months ended March 31, 2018, compared to net cash provided by financing activities of $2.1 million for the three months ended March 31, 2017. The cash flows from financing activities result primarily from funding under an ATM facility in the 2018 period and a share purchase agreement with Lincoln Park Capital in the 2017 period.

Conference Call and Webcast Information

BioLineRx will hold a conference call today, May 22, 2018 at 10:00 a.m. EDT. To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0685 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 May 25, 2018; please dial +1-877-456-0009 from the U.S. or +972-3-925-5942 internationally.

Alpine Immune Sciences to Present at Jefferies 2018 Global Healthcare Conference

On May 22, 2018 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a company focused on discovering and developing innovative, protein-based immunotherapies targeting the immune synapse to treat cancer, autoimmune/inflammatory, and other diseases, reported the company will present at the Jefferies 2018 Global Healthcare Conference on Tuesday, June 5 2018 at 4:30 pm Eastern Time in New York, NY (Press release, Alpine Immune Sciences, MAY 22, 2018, View Source [SID1234526847]).

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A live webcast of the presentation will be available online in the investor relations section of the company’s website at View Source A replay of the presentation will be available on the company website for 90 days following the webcast.

AbbVie to Present at the Jefferies 2018 Global Healthcare Conference

On May 22, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported it will participate in the Jefferies 2018 Global Healthcare Conference on Wednesday, June 6, 2018 (Press release, AbbVie, MAY 22, 2018, View Source [SID1234526846]). Bill Chase, executive vice president and chief financial officer, will present at 7:30 a.m. Central time.

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A live audio webcast of the presentation will be accessible through AbbVie’s Investor Relations website at investors.abbvie.com. An archived edition of the session will be available later that day.

DelMar Appoints Saiid Zarrabian to Full-Time President and CEO

On May 22, 2018 DelMar Pharmaceuticals, Inc. (the "Company")(NASDAQ: DMPI) reported that the board of directors (the "Board") has appointed Saiid Zarrabian as the full-time President and Chief Executive Officer of the Company, effective immediately (Press release, DelMar Pharmaceuticals, MAY 22, 2018, View Source [SID1234526845]). Mr. Zarrabian had previously served as the Company’s interim President and Chief Executive Officer since November 2017 and prior to that as an independent board member since July 2017.

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"Saiid has made significant contributions to DelMar, initially as an independent board member and, most recently, as DelMar’s interim President and CEO. We are pleased that he has agreed to further commit to the Company by taking on the full-time President and CEO role, effective immediately. His contributions have included a renewed focus on our two Phase 2 open label trials for MGMT-unmethylated glioblastoma multiforme, and enhanced fiscal responsibility while advancing our clinical programs in a timely and cost-effective fashion. The Board and I look forward to working with him to build on this momentum," stated Dr. Erich Mohr, Chairman of the Board.

"I am excited to transition from my interim role at DelMar and to continue the clinical advancement of VAL-083, which has been validated in over 40 prior clinical trials indicating VAL-083’s potential to combat multiple devastating diseases for patients with limited alternatives. Although VAL-083 may have applicability to many other solid tumor indications with potentially significant future commercial opportunities, we intend to use a disciplined and stepped approach to investing our resources in pursuing such opportunities. Over the next year, we expect to achieve a number of clinical milestones for VAL-083, including data from the ongoing Phase 2 second-line recurrent GBM study at MD Anderson, as well as data from the international Phase 2 study in newly diagnosed GBM patients. We plan to use our current capital efficiently and to continue to drive the enrollment of our clinical studies in an effort to maximize value for our shareholders," said Mr. Zarrabian.

Mr. Zarrabian is a successful veteran of the biotechnology industry. He previously served as chairman of the board of directors at La Jolla Pharmaceutical Company during the company’s transition from being an OTC listed company to a Nasdaq traded company. He also served as president of the Protein Production Division of Intrexon Corporation, a synthetic biology company. Prior to that, he served as chief executive officer and a member of the board of directors of Cyntellect, Inc., a stem cell processing and visualization instrumentation company until it was acquired in 2012. He served as president and chief operating officer of Senomyx, Inc., a company focused on discovery and commercialization of new flavor ingredients, and as chief operating officer of Pharmacopeia, Inc., a former publicly-traded provider of combinatorial chemistry discovery services and compounds, where he also served as president and chief operating officer of its MSI Division. In addition, Mr. Zarrabian has served on numerous private and public company boards, including at Immune Therapeutics, Inc., Exemplar Pharma, LLC, Ambit Biosciences Corporation, eMolecules, Inc. and Penwest Pharmaceuticals Co. Currently, he is serving as an advisor to Redline Capital Partners, S.A., a Luxemburg-based investment firm.