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Cellectis Publishes Novel Methods to Improve the Safety of CAR T-Cell Therapy and Prevent CRS in the Journal of Biological Chemistry

On February 25, 2019 Cellectis (Euronext Growth: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on allogeneic gene edited CAR T-cells (UCART), reported the publication of a study in The Journal of Biological Chemistry, identifying Granulocyte Macrophage Colony Stimulating Factor (GMCSF) secreted by Chimeric Antigen Receptor (CAR) T-cells as a key factor promoting cytokine release syndrome (CRS) (Press release, Cellectis, FEB 25, 2019, View Source [SID1234533710]). The accelerated report leverages these findings to elaborate an innovative engineering strategy that paves the way for developing safer UCART products.

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Utilizing these results, Cellectis developed engineered GMCSF Knock-Out CAR T-cells through TALEN-mediated gene inactivation. The inactivation of GMCSF in CAR T-cells was found to prevent secretion of pro-inflammatory cytokines by monocytes, without compromising CAR T-cell anti-tumor activity.

"CAR T-cells have achieved high rates of complete remission in hematological malignancies, however, this ‘living drug’ can show life-threatening inflammatory side effects including CRS and neurotoxicity that need to be addressed," said Mohit Sachdeva, Ph.D., Innovation Project Leader at Cellectis. "Our engineering strategy circumvents such toxic side effects and propose safer, equally potent UCART-cells, to improve patients’ quality of life during treatment."

"Today, tocilizumab or glucocorticoid treatments are considered the standard of care for CRS management," added Julien Valton, Ph.D., Innovation Team Leader at Cellectis. "However, these treatments increase patient medication burden, add substantial costs and lengthen treatment time in intense care settings. To overcome these clinical challenges, we investigated the biogenesis of CRS and based on our findings, developed a CAR T-cell product candidate that could potentially prevent rather than treat CRS symptoms. We hope this approach can bypass CRS symptomatic treatments and improve the overall safety of CAR T-cell therapies for cancer patients."

Julien Valton, Ph.D., Innovation Team Leader, Cellular Engineering & Adoptive CAR T-Cell Immunotherapy

Dr. Julien Valton obtained his Ph.D. at the University Joseph Fourier in Grenoble, France, where he was trained as an enzymologist. He then joined the Yale School of Medicine to apply his knowledge to therapeutic research by investigating the mechanism of inhibition of receptor tyrosine kinases that are involved in the development of gastrointestinal cancer. In 2009, he moved a step further into the field of applied science by joining the Innovation Department of Cellectis, where he actively participated in using and improving TALEN gene editing technology for targeted gene therapy and genome engineering. He is now using TALEN along with protein engineering techniques to develop the next-generation CAR T-cells to treat different malignancies.

Mohit Sachdeva, Ph.D., Innovation Team Senior Scientist

Dr. Sachdeva is an experienced cancer biologist with expertise in immuno-oncology, having authored/co-authored approximately 20 manuscripts in peer-reviewed journals throughout his career. During his time at Cellectis, he has been studying pathways that could be exploited to engineer potent, yet safer, CAR T-cells using gene editing and targeted integration technologies. After receiving his Ph.D. at Southern Illinois University, he completed a successful post-doc at Duke University.

Granulocyte-macrophage colony-stimulating factor inactivation in CAR T-Cells prevents monocyte-dependent release of key cytokine release syndrome mediators

Mohit Sachdeva1*, Philippe Duchateau2, Stéphane Depil2, Laurent Poirot2 and Julien Valton1*

1Cellectis, Inc., 430 East 29th Street, New York, NY 10016, USA

2Cellectis, 8 rue de la Croix Jarry, 75013 Paris, France

IMMUNOMEDICS ANNOUNCES RESULTS FOR PERIOD ENDED DECEMBER 31, 2018, STRENGTHENS BOARD, AND FOCUSES MANAGEMENT TEAM

On February 25, 2019 Immunomedics, Inc., (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates (ADC), reported financial results for the Transition Period ended December 31, 2018 (Press release, Immunomedics, FEB 25, 2019, View Source [SID1234533708]). The Company also announced that Dr. Charles Baum, President and Chief Executive Officer (CEO) of Mirati Therapeutics, Inc. has joined the Immunomedics Board of Directors (Board). In addition, the Board has appointed Behzad Aghazadeh, Executive Chairman, while Scott Canute, current member of the Board, has been appointed to Executive Director. At the same time, Michael Pehl has stepped down from the role of President, CEO and member of the Board, due to personal reasons, and interim Chief Financial Officer (CFO), Usama Malik, has been appointed CFO. Please refer to the Company’s Transition Report on Form 10-K filed today with the SEC for more details on the Company’s financial results.

"I would like to thank Michael for his leadership and service to Immunomedics over the past fifteen months. We wish him all the best as he returns to Germany. At the same time, we are honored to welcome Chuck to our Board. Chuck has a storied career in drug development culminating in his role as President and CEO at Mirati, while also serving on the Board of Array Biopharma. Chuck will bring a strong scientific, drug development, and executive management perspective that will be invaluable to Immunomedics as we continue to execute and expand on our development priorities," said Behzad Aghazadeh, Executive Chairman of Immunomedics.

"Our primary focus is to ensure a high-quality Biologics License Application (BLA) resubmission and gain FDA approval of sacituzumab govitecan for patients with metastatic triple-negative breast cancer (mTNBC). To that end, we have implemented a dedicated Complete Response Letter (CRL) team, led by our Executive Board member, Scott Canute, a recognized expert in Manufacturing and Quality spanning decades in the biopharmaceutical industry," Behzad further commented.

"We are committed to working closely with the FDA to resolve the CMC issues identified in the CRL. Based on various prior experiences with much more complex manufacturing challenges at Eli Lilly and Genzyme, I am confident that our expert teams will drive a high-quality and timely resubmission of sacituzumab govitecan," said Scott Canute, Executive Director of Immunomedics.

The CRL team is finalizing a response strategy to the issues identified in the CRL in advance of a meeting request with the FDA and anticipates providing additional clarity on the BLA resubmission timelines after such meeting has occurred.

"Sacituzumab govitecan has demonstrated a significant clinical benefit in multiple hard-to-treat cancer settings", commented Dr. Baum. "I am thrilled to join the Board of Immunomedics and leverage my experience to help navigate the near-term resubmission of the BLA for mTNBC, and shape the clinical development strategy in other late-stage indications," he added.

Dr. Baum is President, CEO and Board Member of Mirati Therapeutics since November 2012. Prior to joining Mirati, he was Senior Vice President for Biotherapeutic Clinical Research at Pfizer and served as the Head of Oncology Development and as Chief Medical Officer for Pfizer’s Biotherapeutics and Bioinnovation Center. He was responsible for the development of the oncology portfolio, including Axitinib (Inlyta), Crizotinib (Xalkori) and the approval of sunitinib (Sutent) for the treatment of gastrointestinal stromal tumor (GIST) and renal cell carcinoma. Previously, Dr. Baum was responsible for the development of several oncology compounds at Schering-Plough, including temozolomide (Temodar) which was approved for the treatment of patients with advanced brain tumors. Dr. Baum currently serves on the Board of Array BioPharma.

Mr. Scott Canute has more than 36 years of experience in the biopharmaceutical industry, previously serving as President of Global Manufacturing and Corporate Operations of Genzyme Corporation from 2010 until 2011, where he led a major turnaround in manufacturing in order to ensure on-going supply of life saving products that were in short supply and developed and implemented a comprehensive manufacturing strategy, including a revamped global governance system. Prior to joining Genzyme, Mr. Canute spent 25 years at Eli Lilly and Company, where he served as President, Global Manufacturing Operations from 2004 until 2007. During his tenure at Eli Lilly, Mr. Canute directed all manufacturing and supply chain activities for the company’s global operations, which spanned 24 international manufacturing sites and 80+ contract manufacturing operations.

Recent Company Highlights

·The Company received a CRL from the FDA for the BLA seeking accelerated approval of sacituzumab govitecan for the treatment of patients with mTNBC who have received at least two prior therapies for metastatic disease.

·The Company published in the New England Journal of Medicine updated data with sacituzumab govitecan in patients with mTNBC, showing a favorable benefit:risk profile of the ADC, as well as providing additional and consistent safety information on 420 patients with a variety of epithelial cancers.

· In an oral presentation at the 2019 Genitourinary Cancers Symposium, the Company reported updated results from a Phase 1/2 study of sacituzumab govitecan in patients with previously treated metastatic urothelial cancer, showing an overall response rate of 31 percent and a median duration of response of 12.9 months in 45 relapsed/refractory patients.

·Enrollment into the pivotal TROPHY U-01 study continues to progress well, while the Company prepares for the initiation of the registrational Phase 3 study in hormone receptor-positive metastatic breast cancer, as well as the Trop-2-enriched basket study.

· The Company has strengthened its manufacturing partnerships with Johnson Matthey and BSP to further enhance the capacity and scale of its supply chain for sacituzumab govitecan in preparation for future demand driven by additional indications and broadening of geographic footprint.

Results for the Transition Period Ended December 31, 2018

On December 14, 2018, the Company’s Board of Directors approved a change in the Company’s fiscal year end from June 30 to December 31, effective immediately. The reporting period for the six months ended December 31, 2018 is referred to as the "Transition Period."

The Company had no revenues in the Transition Period due primarily to the discontinued sale of LeukoScan during the quarter ended March 31, 2018 in order for the Company to focus on its ADC business. Revenues in the comparable period ended December 31, 2017 were approximately $1.3 million.

Total costs and expenses were $144.5 million for the Transition Period, compared to $52.3 million for the comparable period ended December 31, 2017, due primarily to a $51.1 million increase in research and development expenses, a $23.3 million increase in general and administrative expenses, and a $18.4 million increase in sales and marketing expenses. Most of these increases were attributable to activities related to preparations for the potential approval and commercial launch of sacituzumab govitecan for patients with at least two prior lines of treatment for metastatic TNBC in the United States, and to expanded clinical development of sacituzumab govitecan into other indications.

The Company recognized a $1.4 million non-cash income for the Transition Period, compared to a $59.6 million non-cash expense for the comparable period ended December 31, 2017, due to the net appreciation in the fair value of outstanding warrants and the exercise of warrants. There were no warrants outstanding as of December 31, 2018.

Interest expense was $20.0 million for the Transition Period, compared to $2.9 million for the comparable period ended December 31, 2017. The increase was due primarily to increased debt balances as a result of the agreement with RPI Finance Trust.

Net loss attributable to stockholders was $157.7 million, or $0.84 per share, for the Transition Period, compared to $121.3 million, or $0.88 per share, for the comparable period ended December 31, 2017.

As of December 31, 2018, the Company had $497.8 million in cash, cash equivalents, and marketable securities, which it believes is adequate to support its clinical development plan for sacituzumab govitecan; further build its clinical and manufacturing infrastructure and fund its operations through 2020.

Conference Call

The Company will host a conference call and live audio webcast today at 5:00 p.m. Eastern Time to discuss financial results for the quarter and six months ended December 31, 2018 and provide a corporate update. To access the conference call, please dial (877) 303-2523 or (253) 237-1755 using the Conference ID 6478246. The conference call will be webcast via the Investors page on the Company’s website at View Source Approximately two hours following the live event, a webcast replay of the conference call will be available on the Company’s website for approximately 30 days.

Autolus Therapeutics Reports Financial and Operational Results for the Transition Period from October 1 to December 31, 2018

On February 15, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its financial and operational results for the transition period from October 1 to December 31, 2018 (Press release, Autolus, FEB 25, 2019, View Source [SID1234533705]). On December 19, 2018, the board of directors approved a change of fiscal year end from September 30 to December 31. The Company has also filed a report on Form 20-F with the Securities and Exchange Commission for the transition period.

Key recent 2019 events and 2018 highlights include:

Clinical

In February 2019, Autolus announced updated data from the ongoing Phase 1 CARPALL trial of AUTO1 in pediatric patients with relapsed/refractory acute lymphoblastic leukemia (pALL) at the European Hematology Association (EHA) (Free EHA Whitepaper) 1st European CAR T Cell Meeting held in Paris, France. Consistent with the original presentation at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, the emerging safety profile appears to be manageable and differentiated. Notably, none of the patients experienced severe cytokine release syndrome (CRS) (Grade 3-5) and none of the patients required treatment with tociluzumab or steroids. Thirteen patients experienced CRS at Grade 1 or 2. As previously reported, one patient experienced Grade 4 neurotoxicity; there were no other reports of severe neurotoxicity (Grade 3-5). Eleven patients experienced cytopenia that was not resolved by day 28 or recurring after day 28 (Grades 1-4). Two patients developed significant infections, and 1 patient died from sepsis while in molecular complete response (CR). In the trial, AUTO1 combined a high molecular complete response rate (86% after a single dose of AUTO1) with robust persistence at one year follow-up in pediatric acute B cell leukemia patients. The median duration of remission in responding patients was 7.3 months with a median follow-up of 14 months. Event-free survival was 46% with overall survival of 63% at 12 months.

In December 2018, Autolus announced preliminary results from the ongoing Phase 1/2 AMELIA clinical trial of AUTO3 in patients with relapsed/refractory pediatric acute lymphoblastic leukemia (pALL) at the 60th ASH (Free ASH Whitepaper) Annual Meeting in San Diego, California. Researchers reported on ten patients with relapsed or refractory pALL who received an

AUTO3 infusion as a single dose or split dose dependent on their tumor burden. It was observed that AUTO3 was generally well-tolerated with no severe CRS and only one case of Grade 3 neurotoxicity observed, which was considered unlikely related to AUTO3 and primarily attributed to prior intrathecal chemotherapy. Eight out of ten patients achieved minimal residual disease-(MRD) negative CR and higher response rates were observed at doses ³3 x 106/kg dose levels with all patients achieving MRD-negative remission. In the higher dose group, four out of six patients had an ongoing molecular CR as of the cutoff date and, importantly, no loss of CD19 or CD22 was noted among the relapsed patients.

At the 60th ASH (Free ASH Whitepaper) Annual Meeting in December 2018, Autolus also announced preliminary results of the ongoing Phase 1/2 ALEXANDER clinical trial of AUTO3 in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The principal investigator reported that AUTO3 followed by consolidation with a limited duration of anti-PD1 therapy appeared to have a manageable safety profile at the doses evaluated. Out of the seven patients evaluable for safety, none developed CRS grade 3 or higher and one patient had Grade 3 neurotoxicity, considered possibly related to AUTO3. No dose limiting toxicities were observed and dose escalation continues. Six patients were evaluable for response; two patients achieved a CR (which was ongoing at six and three months post-treatment, respectively) and two patients had a partial response; two patients did not respond.

In December 2018, Autolus announced an update on its novel CAR T cell program for peripheral T cell lymphoma. The first patient was dosed in the Phase 1/2 LibrA T1 clinical trial of AUTO4, a developmental therapy for the treatment of relapsed or refractory TRBC1-positive peripheral T cell lymphoma (PTCL). Also, the preclinical data from the sister program AUTO5, targeting TRBC2-positive lymphoma, were presented at the 60th ASH (Free ASH Whitepaper) Annual Meeting.

Autolus will host an R&D Day in New York City on March 26, 2019 for the investment community. This event will provide an update on Autolus’ current clinical programs and highlight the company’s next-generation programed T cell products for hematological and solid tumor indications.

Manufacturing and Product Delivery

In February 2019, the Medicines and Healthcare Products Regulatory Agency approved an extension to the GMP license of the Cell and Gene Therapy Catapult Manufacturing Centre in Stevenage, which, with its innovative operational and licensing model, enables Autolus to manufacture clinical trial supply from this facility.

In January 2019, Autolus announced it has signed a long-term, full-building lease with Alexandria Real Estate Equities, Inc. for the construction and development of an 85,000 square foot build-to-suit facility to be located in the Shady Grove Life Sciences Center in

Rockville, Maryland. The new facility will house offices for Autolus’ U.S.-based research and development, commercial and corporate functions and serve as its first full commercial-scale manufacturing center, with a planned capacity of producing 5,000 T cell therapies annually.

Also in January, Autolus initiated the build-out of a manufacturing facility in Enfield, U.K. The facility is planned to open in 2020 and will provide global supply of viral vector as well as a planned capacity of 1,000 T cell therapies annually.

Autolus is establishing a series of intelligent systems to efficiently manage all aspects of manufacture and certification of supply. Costs will be partly covered through a grant from Innovate UK. To date, Autolus has been awarded Innovate UK grants totaling £6.7 million (approximately $8.6 million).

Corporate Highlights

In December 2018, Autolus announced that it had been selected for addition to the NASDAQ Biotechnology Index (Nasdaq: NBI) as part of the annual re-ranking.

Autolus strengthened its management and board during 2018. Key company management appointments included Andrew J. Oakley as senior vice president and chief financial officer and Adam Hacker, PhD as senior vice president for regulatory affairs and quality. Key board of directors appointments included Linda Bain, current chief financial officer of Codiak BioSciences, Inc., and Cynthia M. Butitta, former chief operating officer of Kite Pharma.

In June 2018, Autolus completed a U.S. initial public offering of American Depositary Shares, representing a total of 10,147,059 ordinary shares, including full exercise of the underwriters’ over-allotment, for net proceeds, after deducting underwriting discounts and commissions and offering expenses, of $156.5 million.

"In 2019, we expect significant progress that will build on the momentum of last year," stated Dr. Christian Itin, chairman and chief executive officer of Autolus. "Our robust pipeline of clinical and pre-clinical programs is progressing well, and we expect to move two programs into registrational trials and provide updates on all of our active programs at conferences during the course of this year. The next scheduled data presentation will be for AUTO1 in adult acute lymphoblastic leukemia at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Annual Meeting in April."

Financial results for the period from October 1 through December 31, 2018:

As stated above, we are transitioning to reporting our results on a calendar year basis, starting with the fiscal year ended December 31, 2018, and as such we are presenting audited results for the three-month period from October 1, 2018 to December 31, 2018, and the comparative period for 2017 discussed below, which is unaudited.

Cash and equivalents at December 31, 2018 totaled $217.5 million, compared with $129.0 million at December 31, 2017, due primarily to the $156.5 million in net proceeds resulting from Autolus’ U.S. initial public offering, which closed in June 2018.

Net total operating expenses for the three months ended December 31, 2018 were $25.0 million, net of grant income of $0.3 million, as compared to net operating expenses of $8.4 million, net of grant income of $0.2 million, for the same period in 2017. The increase in expenses was due, in general, to the increase in clinical trial activity, which is expected to deliver on key milestones in 2019; increased headcount; and the cost of being a public company.

Research and development expenses increased to $17.7 million for the three months ended December 31, 2018 from $5.6 million for the three months ended December 31, 2017. Cash costs, which exclude depreciation as well as share-based compensation, increased to $15.2 million from $5.1 million. The increase in research and development cash costs of $10.1 million consisted primarily of an increase of $4.3 million in project expenses related to the activities necessary to prepare, activate, and monitor clinical trial programs, an increase in compensation-related costs of $3.8 million primarily due to an increase in headcount to support the advancement of our product candidates in clinical development, and an increase of $2.0 million in facilities costs and consumables supporting the expansion of our research and translational science capability and investment in manufacturing facilities and equipment.

General and administrative expenses increased to $7.6 million for the three months ended December 31, 2018 from $3.1 million for the three months ended December 31, 2017. Cash costs, which exclude depreciation as well as share-based compensation, increased to $5.7 million from $2.5 million. The increase of $3.2 million consisted primarily of an increase of $2.3 million in insurance, patent costs, commercial costs, investor relations and communication costs and additional facility costs, as well as an increase in compensation-related expense of $0.9 million.

Net loss attributable to ordinary shareholders was $20.6 million for the three months ended December 31, 2018, compared to $7.5 million for the same period in 2017.

The basic and diluted net loss per ordinary share for the three months ended December 31, 2018 totaled $(0.52) compared to a basic and diluted net loss per ordinary share of $(0.26) for the three months ended December 31, 2017.

Autolus anticipates that cash on hand provides a runway into calendar year 2021.

Conference Call and Presentation Information

Autolus management will host a conference call today, February 25, at 8:00 a.m. EST/ 1:00pm GMT to discuss the company’s financial results and operational update.

To listen to the webcast and view the accompanying slide presentation, please go to: View Source

The call may also be accessed by dialing 877-270-2148 (U.S.) and 412-902-6510 (international) and asking the operator to join the Autolus Therapeutics conference call. After the conference call, a replay will be available for one week. To access the replay, please dial 877-344-7529 (U.S.) or 412-317-0088 (international) and enter replay access code 10129000.

VBI Vaccines Provides Corporate Update, Outlook for 2019, and Year-End 2018 Financial Results

On February 25, 2019 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported its financial results for the fourth quarter and twelve months ended December 31, 2018 (Press release, VBI Vaccines, FEB 25, 2019, View Source [SID1234533674]).

"2018 was a foundational year, one that laid critical groundwork as we build towards the transformational milestones expected in 2019," said Jeff Baxter, President and CEO, VBI Vaccines Inc. "Our achievements in 2018 – which included the launch of the collaboration with Brii Biosciences to develop a functional cure for Hepatitis B for up to $129 million plus royalties, the closing of a $42.9 million public offering led by Perceptive Advisors, the positive Phase 1 data readout from our cytomegalovirus (CMV) vaccine candidate, and encouraging early immunogenicity data from the Phase 1/2a of our glioblastoma (GBM) immuno-therapeutic – set the stage for 2019. Heading into this year, VBI is well-positioned to achieve meaningful clinical milestones across all of our lead programs, most notably the top-line data readout from the PROTECT Phase 3 study of Sci-B-Vac expected in four months’ time."

Sci-B-Vac Program Update (Prophylactic Hepatitis B):

In December 2017, the Company initiated enrollment in two pivotal Phase 3 clinical studies – PROTECT and CONSTANT – in a total of approximately 4,500 adults. The studies were designed to assess safety and efficacy of Sci-B-Vac, VBI’s prophylactic hepatitis B (HBV) vaccine that is the only commercially-available trivalent HBV vaccines containing Pre-S1, Pre-S2, and S antigens and adjuvanted with alum.

"Hepatitis B remains a serious public health unmet need, one where enhanced protection through vaccination is vital for long-term control," said Francisco Diaz-Mitoma, M.D., Ph.D., VBI’s Chief Medical Officer. "In the last two decades, Sci-B-Vac has been tested in 22 different clinical trials and has been safely and effectively administered to over 500,000 infants and adults in the commercial setting. We believe the extensive safety and efficacy data we have to-date has largely de-risked the ongoing Phase 3 studies. We look forward to the data readouts later this year, as we work to provide a rapid, potent, and safe hepatitis B vaccine to address this significant unmet infectious disease need."

Upcoming Sci-B-Vac Clinical Data Read-outs:

●Mid-year 2019: PROTECT Phase 3 top-line data

PROTECT is a head-to-head immunogenicity study in approximately 1,600 subjects comparing Sci-B-Vac to Engerix-B.
Primary endpoints include non-inferiority of Sci-B-Vac in adults over age 18, and superiority of Sci-B-Vac in adults over age 45.
Secondary endpoints include non-inferiority of Sci-B-Vac after two vaccinations compared with three vaccinations of Engerix-B, and safety.

●Around year-end 2019: CONSTANT Phase 3 top-line data

CONSTANT is a lot-to-lot consistency study in approximately 2,850 subjects comparing immune responses across three independent, consecutively manufactured lots of Sci-B-Vac.
Secondary endpoints include safety, and efficacy compared with Engerix-B

Other Pipeline Program Updates:

GBM Immuno-therapeutic:

VBI-1901, an immuno-therapy developed using VBI’s proprietary enveloped virus-like particle (eVLP) technology platform, is being assessed in an ongoing phase 1/2a clinical study in recurrent GBM patients. In 2018, VBI completed enrollment in all three dose cohorts in the Part A dose-escalation phase of the study, with six patients enrolled in each cohort. In February 2019, the independent Data and Safety Monitoring Board (DSMB) reviewed all safety data from Part A and unanimously recommended the continuation of the study without modification.

"While Part A of the study was primarily designed to assess safety and tolerability of VBI-1901 to support the identification of the optimal therapeutic dose level for Part B of the study, we are encouraged by the early immunogenicity data we’ve observed to-date," said David Anderson, Ph.D., VBI’s Chief Scientific Officer. "Part B of the study will have narrower enrollment criteria and is primarily designed to assess efficacy signals of VBI-1901 in recurrent GBM patients. With a more homogenous patient cohort in Part B, we look forward to identifying potential initial correlations between immunologic responses and clinical outcomes by year-end 2019."

Upon selection of the optimal dose level in Part A, based on safety and immunogenicity data, the Company expects to initiate enrollment of an additional 10 patients in the subsequent Part B extension phase of the study. Expanded immunologic data and 6-month survival data from all dose cohorts in the Part A dose-escalation phase are expected later in the first half of 2019.

Hepatitis B Immuno-therapeutic:

In December 2018, VBI announced a license and collaboration agreement with Brii Biosciences, for up to $129 million plus royalties, for the development of a functional cure for the treatment of chronic hepatitis B infection using VBI-2601. VBI-2601 is a novel immuno-therapeutic candidate that is uniquely formulated to target B- and T-cell immunity by neutralizing circulation of the hepatitis B virus, blocking hepatitis B infection of hepatocytes through Pre-S1 immunity, and enabling immune-mediated clearance of HBV-infected hepatocytes.

As part of this collaboration, clinical proof of concept studies are expected to be initiated by the end of 2019.

CMV Prophylactic Vaccine:

In May 2018, VBI announced positive top-line data from the Phase 1 study of VBI-1501, the Company’s prophylactic vaccine candidate for CMV. The Phase 1 top-line data showed that VBI-1501 was safe and well-tolerated at all doses and was immunogenic, even at the lower doses tested. In December 2018, VBI announced plans for a formal Phase 2 dose-ranging study to assess safety and immunogenicity of VBI-1501 at higher doses. The highest dose level is expected to be 10-times higher than that tested in the Phase 1 study.

The Company expects to initiate enrollment in the Phase 2 study by the end of 2019, following the requisite toxicology studies.

Financial Results for the Three and Twelve Months Ended December 2018:

○VBI ended the fourth quarter of 2018 with $59.3 million cash and cash equivalents compared with $67.7 million as of December 31, 2017. Net cash used in operating activities for the full year 2018 was $45.5 million, compared to $31.4 million for the same period in 2017. Additionally, the purchase of property and equipment in 2018 was $6.0 million compared with $0.6 million in 2017. This increase was due to the modernization and capacity increase of the Rehovot site, where all clinical and commercial supplies of Sci-B-Vac are manufactured, to enable the supply of commercial quantities of Sci-B-Vac upon marketing authorization approval by the FDA, EMA, and/or Health Canada. As part of this modernization and capacity increase, the site was temporarily shut down as of April 22, 2018. The construction related to the modernization and capacity increase is ongoing, and validation activities are in progress.

○Revenue for the fourth quarter of 2018 was $2.7 million, and was primarily attributable to amounts recognized as part the therapeutic Hepatitis B license and collaboration agreement with Brii Biosciences. Revenue for the fourth quarter of 2017 was $0.2 million and was primarily attributable to sales of Sci-B-Vac in Israel. Product sales in 2018 were $0.6 million compared with $0.5 million in 2017. The change was due to an increase in product sales related to the Sci-B-Vac named-patient program in Europe, offset by a slight decrease in Sci-B-Vac sales in Hong Kong and Israel.

○Cost of Revenue for the full year 2018 was $4.5 million compared with $5.2 million for the full year 2017. This decrease was due to the Rehovot site shut-down, resulting in limited production activity, reduced maintenance and utilities expenses, and allocation of some overhead to general and administrative expenses.

○Research and development expenses for the fourth quarter and full year 2018 were $10.1 million and $38.5 million, respectively. Research and development expenses for the same periods in 2017 were $6.5 million and $20.9 million, respectively. The increase was driven by the initiation and execution of the two Sci-B-Vac Phase 3 trials and the GBM Phase 1/2a clinical trial, which are currently ongoing.

○General and administrative expenses for the fourth quarter and full year 2018 were $9.9 million and $20.8 million, respectively. General and administrative expenses for the same periods in 2017 were $3.4 million and $12.0 million, respectively. The increase was primarily attributable to a $6 million payment made in December 2018 to re-obtain a distribution agreement with a third party who previously held certain distribution rights to certain Asian markets.

○Net loss and net loss per share for the year-end 2018 were $63.6 million and $0.97, respectively, compared to a net loss of $39.0 million and a net loss per share of $0.88 for the year-end 2017

Exicure Announces Dosing of First Patient in Phase 1b/2 Immuno-oncology Trial

On February 25, 2019 Exicure, Inc. (OTCQB: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported that it has dosed the first patient in its multicenter, open-label, Phase 1b/2 study of AST-008 combined with pembrolizumab (Press release, Exicure, FEB 25, 2019, View Source;p=RssLanding&cat=news&id=2388720 [SID1234533672]). Enrollment in the trial is open to patients with superficial injectable tumors in advanced or metastatic solid tumor conditions including Merkel cell carcinoma, head and neck squamous cell carcinoma, cutaneous squamous cell carcinoma and melanoma. clinicaltrials.gov NCT03684785

"We believe that combining our immune system agonist drug with checkpoint inhibitors is an important strategy for leveraging the patient’s own immune system to fight cancer. We are excited to bring this approach into cancers like Merkel cell carcinoma, where patients have limited success using currently available treatments," said Exicure CEO Dr. David Giljohann. "It is also an important milestone for Exicure in the development of our platform technology, which allows us to digitally design drug candidates and potentially bring them into clinic faster."

The primary objective of the Phase 1b dose escalation stage is to assess the safety and tolerability of Exicure’s AST-008 drug alone and in combination with pembrolizumab, and to determine a dose for the Phase 2 stage of the study. Patients in the dose escalation stage may have previously been exposed to antibody checkpoint inhibitors, but not as a requirement for inclusion in the trial. In the Phase 2 portion of the study, Exicure will further evaluate AST-008 in combination with pembrolizumab in patients who have previously received but not responded to anti-PD-1 or anti-PD-L1 antibody therapy.

About Exicure’s AST-008 Drug

AST-008 is a toll-like receptor nine (TLR9) agonist oligonucleotide in a proprietary SNA format with immune-stimulatory properties. SNAs are dense, radial arrangements of nucleic acids (DNA) that have high cellular uptake and an enhanced presentation of the DNA for TLR9 agonism. AST-008 is designed to enter into and activate immune cells to elicit an immune response to treat solid tumors in combination with other agents such as checkpoint inhibitors. We observed that AST-008 showed potent antitumor activity as a monotherapy and synergized with anti-PD-1 antibodies in multiple preclinical tumor models. In a successful Phase 1 trial in healthy volunteers, AST-008 activated key immune cells and cytokines predictive for an anti-tumor effect in patients.