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VBI Vaccines Provides Corporate Update, Outlook for 2020, and Year-End 2019 Financial Results

On March 5, 2020 VBI Vaccines Inc. (Nasdaq: VBIV) ("VBI"), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported a corporate update, its outlook for 2020, and financial results for the fourth quarter and twelve months ended December 31, 2019 (Press release, VBI Vaccines, MAR 5, 2020, View Source [SID1234555215]).

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Annual Note from Jeff Baxter, President and CEO:

"Over the last 18 months, VBI has transformed into a company committed to changing the landscape of hepatitis B (HBV) by improving prevention and working to develop a functional cure. HBV is a significant global public health issue with an increasing disease burden – by example, the acute HBV infection rate in the US increased by 20.7% in 2015, rising for the first time since 2006, with the sharpest increases occurring largely in states that have been impacted most by the ongoing opioid epidemic1. More than that, HBV is often an asymptomatic virus – it is estimated that as many as 67% of people with chronic HBV in the US are unaware of their infection status2. All of this underlines the importance of vaccination against HBV.

"Our trivalent hepatitis B vaccine, Sci-B-Vac, has successfully completed the pivotal Phase 3 program, demonstrating its ability to safely and rapidly elicit robust immune responses, conferring seroprotection in adults, including those who have been harder to protect, namely older adults, diabetics, and obese individuals. We are now working with the FDA and other regulatory agencies to prepare for submissions of regulatory approval applications in the US, Europe, and Canada, beginning in the fourth quarter of 2020. We believe Sci-B-Vac has the potential to be an efficacious, safe, and cost-effective option for all adults seeking protection against HBV.

"While we believe prevention is always better, and more cost-effective, we also recognize the importance of a cure for HBV. Recent estimates of people chronically-infected with HBV worldwide range from 240 million to 350 million, with over 2 million in the US alone3; globally, more than 2 billion people have ever been infected with HBV, acutely or chronically4. The race to develop a functional cure for HBV is competitive, but we believe consensus amongst experts is building that an immunotherapeutic would be needed to achieve long-term immunologic control and restore the body’s defense against HBV. With our new trivalent formulation that enhances T-cell response, we believe VBI-2601 (BRII-179) is well-positioned to be the immunotherapeutic component of a functional cure. Initial data from the ongoing Phase 1b/2a clinical study for VBI-2601, conducted with our partner Brii Biosciences (Brii Bio), are expected in the second half of 2020.

"In our other programs, we are integrating our cytomegalovirus (CMV) expertise with our proprietary enveloped virus-like particle (eVLP) technology to develop therapeutic cancer vaccines and prophylactic vaccines. Our lead eVLP program, VBI-1901, targets the most aggressive form of adult brain cancer, glioblastoma (GBM), a CMV-associated solid tumor. GBM is a devastating disease leaving patients with few treatments options. Encouraging data from the ongoing Phase 1/2a study in recurrent GBM patients were presented throughout 2019, with demonstrated correlations between immunologic responses, tumor responses (assessed through MRI scans), and clinical responses (survival data). As a testament to the strength of the early data, we entered into a collaboration with GlaxoSmithKline (GSK) to clinically evaluate the combination of VBI-1901 with GSK’s proprietary AS01B adjuvant system, a highly-innovative adjuvant system that has contributed to positive results in GSK’s shingles vaccine, Shingrix. We expect additional data from Part B of the ongoing Phase 1/2a study throughout 2020. We hope to continue to see encouraging results from VBI-1901 as we work hard to provide meaningful benefit to these patients.

"There were numerous clinical milestones throughout 2019, but we believe 2020 will be an even more transformational year for the company. The VBI team in the US, Canada, and Israel are working hard to address significant unmet medical needs, and we believe this dedication and focus on successfully achieving fundamentals will drive shareholder value. We appreciate the continued shareholder support as well as that of our partners and volunteers who participate in our clinical trials, and we look forward to continued advancement and achievement in 2020 and beyond."

Recent Key Program Achievements and Projected Upcoming Milestones:

Sci-B-Vac: Trivalent Prophylactic HBV Vaccine

●June 2019 and January 2020 : Announcement of positive top-line results from both pivotal Phase 3 studies which, combined, showed:

oNon-inferiority of seroprotection rate (SPR) in all adults ≥ age 18 compared with Engerix-B;
oSuperiority of SPR in adults ≥ age 45 compared with Engerix-B;
oHigher SPR in all key subgroup analyses of adults ≥ 18 years, including by age, gender, body mass index, diabetic status, and smoking status, compared with Engerix-B;
oHigher SPR at all time points compared to Engerix-B and, in CONSTANT, non-inferiority of SPR after 2 doses of Sci-B-Vac compared with 3 doses of Engerix-B in adults age 18-45 years;
oLot-to-lot manufacturing consistency; and
oSafety and tolerability consistent with the known safety profile of Sci-B-Vac, with no new safety risks identifies and no safety signals observed.

●Q2 2020 : Pre-BLA discussions expected with the FDA.
●Q4 2020 : Submission of applications for regulatory approvals in the US, Europe, and Canada expected to begin.

VBI-2601 (BRII-179): HBV Immunotherapeutic Candidate

●November 2019 : Initiation of enrollment in Phase 1b/2a study in patients with chronic HBV infection. The Phase 1b/2a is a randomized, controlled study designed to assess the safety, tolerability, antiviral, and immunological activity of VBI-1901 (BRII-179). The study is expected to enroll up to 65 patients and is sponsored by our partner Brii Bio.
●H2 2020 : Initial human proof-of-concept data expected from Phase 1b/2a study.

VBI-1901: Cancer Vaccine Immunotherapeutic Candidate

●June 2019, November 2019, and March 2020: Encouraging data from the ongoing Phase 1/2a clinical study of VBI-1901 in recurrent GBM patients were announced, demonstrating that:

oVBI-1901 is well-tolerated at all doses tested, with no vaccine-related safety signals observed;
oTwo patients in the high-dose cohort of Part A experienced a 60% reduction in the size of the primary tumor;
oIn the high-dose cohort of Part A, vaccine response correlated with clinical response, with a 12-month overall survival (OS) rate of 83% (n=5/6) for vaccine responders vs. 33% (n=3/9) for non-responders – vaccine responders also saw a 6.25-month improvement in median OS (14.0 months) compared with vaccine non-responders (7.75 months); and
oEarly tumor and immunologic responses in Part B aligned with responses and benefit observed in Part A.

●September 2019 : Announcement of collaboration with GSK to clinically evaluate VBI-1901 in combination with AS01B as a second arm in Part B of the ongoing Phase 1/2a study in first-recurrent GBM patients
●February 2020 : Enrollment initiated in VBI-1901 + GSK’s AS01B study arm
●Q2 2020 : Expanded immunologic, tumor, and clinical data expected from Phase 2a VBI-1901 + GM-CSF study arm
●Q4 2020 : Initial immunologic and tumor response data expected from Phase 2a VBI-1901 + AS01B study arm

Financial Results for the Three and Twelve Months Ended December 2019

●Cash Position: VBI ended the fourth quarter of 2019 with $44.2 million cash and cash equivalents compared with $59.3 million as of December 31, 2018.
●Net Cash Used in Operating Activities: Net cash used in operating activities for the full year 2019 was $48.7 million, compared to $45.5 million for the same period in 2018.
●Cash Used for Purchase of Property and Equipment: The purchase of property and equipment in 2019 was $3.7 million, compared to $6.0 million in 2018, and was primarily in Rehovot, Israel, as part of the modernization and capacity increase of the manufacturing facility. As part of this process, manufacturing at the facility in Rehovot, Israel, was temporarily shut-down in 2018 and re-commenced in May 2019. Following completion of the modernization and capacity increase, VBI received the certificate of Good Manufacturing Practice (GMP) compliance from the Israeli Ministry of Health in January 2020.
●Revenue: Revenue for the three months ended December 31, 2019 and for the full year 2019 was $0.6 million and $2.2 million, respectively, compared to $2.7 million and $3.4 million for the same time periods in 2018, respectively. The decrease in revenue was due to decreased named-patient product sales in Europe in 2019. Additionally, there was a decrease as a result of the license revenue earned as part of the License Agreement with Brii Bio in 2018, but this was offset by an increase in R&D services revenue in 2019 as part of the same agreement with Brii Bio.
●Research and Development (R&D): R&D expenses for the fourth quarter and full year 2019 were $4.3 million and $26.3 million, respectively, compared to $10.1 million and $38.5 million for the same periods in 2018, respectively. The decrease in R&D spend in 2019 was primarily due to a decrease in costs as the Phase 3 program for Sci-B-Vac neared completion.
●General and Administrative (G&A): G&A expenses for the fourth quarter and full year 2019 were $3.8 million and $14.1 million, respectively, compared to $9.9 million and $20.5 million for the same periods in 2018, respectively. The decrease in G&A expense in 2019 was primarily due to a $6 million payment made in 2018 to re-obtain Sci-B-Vac distribution rights in Asia, with no similar payment made during 2019. Other variances include decreased administrative expenses and the re-allocation of expenses from G&A back to Cost of Goods in 2019 related to the temporary Rehovot facility closure.
●Impairment Charge: There was an impairment charge of $6.3 million in 2019 related to goodwill, compared to $0.3 million in 2018.
●Net Loss: Net Loss and net loss per share for the year ended December 31, 2019 were $54.8 million and $0.46, respectively, compared to a net loss of $63.6 million and a net loss per share of $0.97 for the year ended December 31, 2018.

TG Therapeutics Receives Orphan Drug Designation for Umbralisib from the U.S. Food and Drug Administration for the Treatment of Follicular Lymphoma

On March 5, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX) reported that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to umbralisib, the Company’s investigational dual inhibitor of PI3K-delta and CK1-epsilon, for the treatment of patients with follicular lymphoma (FL) (Press release, TG Therapeutics, MAR 5, 2020, View Source [SID1234555214]).

Umbralisib is being evaluated across several types of lymphoma in the UNITY-NHL Phase 2b registration directed clinical trial. The FL cohort of the UNITY-NHL trial is designed to evaluate the safety and efficacy of umbralisib in patients with FL who have received at least two prior lines of therapy including an anti-CD20 monoclonal antibody and an alkylating agent. In October 2019, the Company announced that the FL cohort met the primary endpoint of overall response rate (ORR), and in January the Company initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for umbralisib as a treatment for patients with previously treated marginal zone lymphoma (MZL) and FL.

The FDA has previously granted orphan drug designation to umbralisib, for the treatment of patients with all three types of MZL: nodal, extranodal, and splenic MZL.

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics, stated, "The receipt of orphan drug designation for umbralisib to treat patients with FL is another important milestone in the development and anticipated commercialization of umbralisib in MZL and FL." Mr. Weiss continued, "We were pleased to announce last year that both the MZL and FL cohorts of the UNITY-NHL trial met their primary endpoints and have commenced our first rolling submission for these indications. We are excited by the progress so far and look forward to completion of this submission targeted in the first half of this year."

ABOUT ORPHAN DRUG DESIGNATION

Orphan drug designation is granted by the U.S. FDA to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain incentives which may include tax credits towards the cost of clinical trials and prescription drug user fee waivers. If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity.

ABOUT FOLLICULAR LYMPHOMA

Follicular lymphoma (FL) is typically a slow-growing or indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes, making it a B-cell lymphoma. Follicular lymphoma is generally not curable and is a chronic disease. Patients can live for many years with this form of lymphoma. With an annual incidence in the United States of approximately 15,000 newly diagnosed patients1, FL is the most common indolent lymphoma accounting for approximately 20 percent of all NHL cases2.

ABOUT THE UNITY-NHL PHASE 2b STUDY—FOLLICULAR LYMPHOMA COHORT

The multicenter, open-label, UNITY-NHL Phase 2b study follicular lymphoma (FL) cohort was designed to evaluate the safety and efficacy of single agent umbralisib in patients with FL who have received at least two prior lines of therapy, including an anti-CD20 regimen and an alkylating agent. The primary endpoint is overall response rate (ORR) as determined by Independent Review Committee (IRC) assessment. Secondary endpoints include safety, duration of response, and progression-free survival (PFS).

In October of 2019, the Company announced that the primary endpoint of ORR as determined by IRC was met for all treated FL patients (n=118). The results met the Company’s prespecified response target of 40-50% ORR. In January of 2020, the Company announced the initiation of a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) requesting accelerated approval of umbralisib as a treatment for patients with previously treated marginal zone lymphoma (MZL) and follicular lymphoma (FL).

AI reveals differences in appearance of cancer tissue between racial populations

On March 5, 2020 Scientists at Case Western Reserve University reported that using Artificial Intelligence (AI) to reveal apparent cellular distinctions between black and white cancer patients, while also exploring potential racial bias in the rapidly developing field of AI.

Their most recent published research asserts that AI analysis of digitized images of cancer tissues reveals critical variations between black and white male prostate cancer patients. The work also suggests the new population-specific information—in addition to image detail on tissue slides also analyzed by computers—could substantially improve care for black patients with prostate cancer.

Anant Madabhushi, professor
Anant Madabhushi
"On one level, we’re simply trying to understand and answer this question: ‘Are there biological differences in the disease, in the cancer, that are a function of your ethnicity or your race?’" said Anant Madabhushi, the F. Alex Nason Professor II of Biomedical Engineering at Case Western Reserve and senior author on a study published today in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). "In other words, is there something else going on that can’t be explained by other disparities? The answer appears to be, ‘yes.’"

This new work on prostate cancer builds on mounting evidence that clear biological differences between races can be discovered at a cellular level in the analysis of cancer cells—information which can be useful to tailor medical care to specific groups and individuals within those populations.

$3.2M in three new grants from the Department of Defense

Madabhushi and his lab, along with collaborators from the Case Western Reserve School of Medicine, University of Washington Seattle and Perelman School of Medicine at the University of Pennsylvania, have also been awarded $3.2 million in three grants from the U.S. Department of Defense to assess biological differences in prostate and breast cancers between black and white patients:

— Sanjay Gupta, Carter Kessell Associate Professor of Urology at the Case Western Reserve School of Medicine and Madabhushi were awarded $1.6 million to study how AI might be used to explore differences at the morphologic and molecular level of prostate cancer between black and white men.

— Madabhushi, Jonathan Liu at the University of Washington-Seattle and Dr. Priti Lal at the Perelman School of Medicine at the University of Pennsylvania were awarded $1 million to develop new approaches to understand biological differences between prostate cancer appearance in black and white men. The grant will involve a new technique pioneered by Liu’s group called "light sheet microscopy tissue imaging," which uses AI and 3D technology to view tumors in an entirely new way, Madabhushi said.

— Cheng Lu, an assistant research professor in Madabhushi’s Center for Computational Imaging and Personalized Diagnostics, and collaborators, were awarded a three-year $570,000 grant to use AI to study differences in appearance of tissue biopsy images of triple-negative breast cancer, a very aggressive form of breast cancer, between black and white women.

Implicit in all of the ongoing research, Madabhushi said, is the larger question about whether the racial differences being discovered at the cellular level are revealing a research bias at the human level.

"Even as we do this groundbreaking research, we can’t allow ourselves to get trapped into trusting these models blindly," he said, "so we need to question whether we are considering all populations (and) ask how diverse our research pool is."

Prostate cancer study
Racial differences were a key component in the most recent research work. The prostate cancer study was performed over three years at six sites and involved nearly 400 men with the disease.

One of the critical questions in management of prostate cancer patients is to identify which men following prostate surgery are at higher risk of disease recurrence and could benefit from adjuvant therapy.

The patient pool in this study, however, was about 80% white and 18% black, "so the model was biased toward the majority population," Madabhushi said. "Once we found the variations, applying the model to all would be doing a disservice to that one population."

Once researchers created a race-specific model, the accuracy in determining which black patients would have a recurrence of the cancer increased six-fold, Madabhushi said.

Like previous cancer research led by Madabhushi’s lab, the scientists asked the computer to look for patterns not only from images of the tumor itself, but at tissue outside the tumor, known as the stroma.

In doing so—in this and other cancer studies—they have been able to successfully tell, among other things, which patients would respond well to chemotherapy, immunotherapy or even, in some cases, whether cancer would return or how long a patient might live.

Aside from non-melanoma skin cancer, prostate cancer is the most common cancer among men in the United States and one of the leading causes of cancer death among men of all races, according to the Centers for Disease Control.

Further, while surgical resection of the prostate—known as a radical prostatectomy—is performed for about 75,000 newly diagnosed patients each year, 30% to 40% will see the cancer return, Madabhushi said.

In this case, armed with the knowledge of which patients had a recurrence of the cancer, scientists were able to retroactively see visual signals in tissue slides from their initial diagnosis to determine which patients would suffer that recurrence.

Lead authors who collaborated with Madabhushi on the paper included Hersh Bhargava, a PhD student at the University of California-San Francisco and Patrick Leo, a graduate student of biomedical engineering at Case Western Reserve University.

Bhargava said the researchers were able to "look at, and actually measure, hundreds of thousands, even millions, of cancer cells to see features that a human could never see—including structural characteristics."

"It’s clear from the existing scientific literature that there are racial disparities in all cancers, but it appears that especially in prostate cancer that those differences can’t be explained by access to care or socioeconomic status—but rather that there is a biological component to how the cancers manifest differently between black and white patients."

Leo said that the research was focused on a population-disparities element that has not been recognized until now in what he called the "AI-for-health space."

"We know now that the risk is that if you just build a model for all patients, you will actually perform worse for patients in the minority and that’s something we cannot accept, even if it’s not something we did intentionally. So, if you want a model to work on patients from all populations, you have to deliberately include a population-specific aspect."

Orionis Biosciences Debuts with Major Pharmaceutical Collaboration to Tackle Industry’s Most Challenging Protein Targets

On March 5, 2020 Orionis Biosciences is reported with the announcement of a major drug discovery collaboration with Novartis (Press release, Orionis Biosciences, MAR 5, 2020, View Source [SID1234555212]). Orionis has developed innovative technologies in genome-scale drug discovery and tunable molecular design of novel therapeutic drug modalities to tackle the industry’s most intractable disease targets.

The goal of the four-year collaboration with Novartis is to discover and design novel small molecule therapeutics, such as protein degraders, across various therapeutic areas, by broadly leveraging Orionis’ Allo-Glue technology platform. The terms of the collaboration include research funding, a convertible note investment, royalties and potential clinical milestones.

"Our collaboration with Novartis provides tremendous validation of the work we have accomplished over the past several years to develop innovative tools to unlock challenging drug targets for new therapeutic modalities," commented Niko Kley, CEO of Orionis. "There are many disease-related targets that have eluded scientists and drug discoverers for decades, with new ones being identified every day. Our proprietary genome-wide discovery and drug design technologies may enable identification and development of small molecules and biologics with high specificity and selectivity against targets at a scale, speed and efficiency that is unique in the industry."

Orionis was originally founded by drug discovery and technology pioneers Niko Kley, PhD, CEO, Jan Tavernier, PhD, CTO and Professor at VIB-Ghent University (Belgium), and VIB. Riccardo Sabatini, PhD, CDS, joined the company as architect and leader of Orionis’ computational science platform.

Dr. Jay Bradner, MD, PhD, President of the Novartis Institutes for BioMedical Research commented, "We are excited to be working with the Orionis team to combine our expertise in drug discovery and development with their innovative technologies for rapidly identifying and prioritizing new targets at a genome-wide scale. Our hope is that through this collaboration, we will be able to reach historically elusive targets as we strive to bring new therapies to patients more quickly."

Riccardo Sabatini commented further, "It is incredibly exciting to see how mapping of genome-scale fingerprints of drug action is opening new possibilities and dimensions in applications of numerical methods and machine learning to support drug design."

"The opportunity behind the forming of Orionis was that the existing pharmacopeia of approved drugs reflects relatively few disease targets being addressed with too many similar drugs. We have been steadily executing on our mission to bring together an array of technological innovations to enable discovery of a diversity of new drug candidates that act with high therapeutic target-focused precision," commented Prof. Jan Tavernier.

Orionis Biosciences, named for the Orion star system, is a unique constellation of people, technology platforms and drug modalities. "We have quietly built and evolved our core science capabilities, portfolio of intellectual property and an exciting emerging pipeline of drug candidates, which we are advancing to unlock major value for the pharmaceutical industry and new treatment options for patients in need," commented CEO Niko Kley.

About Allo-Glue Technology
Allo-Glue molecules are a unique class of allosterically acting small molecules that enable access to targets previously thought unapproachable. They act to alter the form and function of, and thereby reprogram, intracellular proteins to engage in molecular interactions that modulate disease target proteins, including promoting their degradation by a cell’s natural protein disposal machinery.

PsiOxus Therapeutics Announces Clinical Trial with Third Cancer Gene Therapy Treatment and Appointment of New Chief Medical Officer

On March 5, 2020 PsiOxus Therapeutics, Ltd. (PsiOxus), the gene therapy for cancer company, reported that it has started a clinical trial with NG-641, a four transgene tumor-microenvironment modifying cancer gene therapy, to cancer patients (Press release, PsiOxus Therapeutics, MAR 5, 2020, View Source [SID1234555209]). This is the first time that a tumor-specific virus containing four different therapeutic transgenes has been administered to cancer patients.

PsiOxus also announced today that Dr Tom Lillie has been appointed as Chief Medical Officer. Dr Lillie, who previously held senior oncology roles at Amgen and then MSD (known as Merck in the USA and Canada), where he was most recently Vice President, Oncology Global Medical Affairs, will be based in their Oxford, UK Head Office.

"With NG-641, our approach of systemically delivering gene therapy vectors to turn tumor cells into drug factories is being deployed to deliver a bispecific T-cell activating protein to target cancer-associated fibroblasts (CAFs) via the fibroblast activation protein (FAP). This mechanism allows us to target one of the most important immunosuppressive cells in the tumor microenvironment" stated Dr Brian Champion, the Chief Scientific Officer of PsiOxus.

In addition to the FAP-targeted T-cell activator, NG-641 also delivers three other molecules to further recruit and activate T-cells to induce an anti-tumor immune response. NG-641 is thus the first quadrivalent viral gene therapy vector for cancer to be studied in patients.

The Phase 1 STAR study is being conducted at multiple cancer centers in the United States and will assess the safety, tolerability and preliminary anti-tumor activity of NG-641 in subjects with solid tumors. The ClinicalTrials.gov identifier for the NG-641 study is: NCT04053283. A link to the ClinicalTrials.gov listing for the study can be found here.

Dr John Beadle, Chief Executive Officer of PsiOxus stated, "It is a great pleasure to welcome Dr Tom Lillie to our leadership team. He brings exceptional expertise related to cancer drug development and immunotherapy including the clinical development, launch and marketing of oncolytic viruses and checkpoint inhibitors".

Dr Tom Lillie added, "I am pleased to join PsiOxus at this exciting time as our third cancer gene therapy enters clinical evaluation. I look forward to the opportunity to work with the rest of the PsiOxus team as we continue to develop innovative gene therapy products to treat and benefit cancer patients."

PsiOxus’ proprietary T-SIGn platform uses the enadenotucirev oncolytic virus as a vector to deliver combinations of therapeutic transgenes to carcinomas to fight cancer. All T-SIGn products are administered intravenously and are designed to selectively infect and replicate only in tumor cells. NG-348 and NG-350A are PsiOxus’ other T-SIGn viruses which have entered clinical trials.