On March 5, 2020 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported that it will host a conference call and live audio webcast on Thursday, March 12, 2020 at 4:30 p.m. Eastern Time to discuss financial results for the fourth quarter and year ended December 31, 2019 and to provide a business update (Press release, CymaBay Therapeutics, MAR 5, 2020, View Source [SID1234555218]).

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

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

                  Schedule Your 30 min Free Demo!

Conference Call Details
To access the live conference call, please dial 855-327-6837 from the U.S. and Canada, or 631-891-4304 internationally, Conference ID# 10008868. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source

On March 5, 2020 Fennec Pharmaceuticals Inc. (Nasdaq: FENC; TSX: FRX), a specialty pharmaceutical company focused on the development of PEDMARKTM (a unique formulation of sodium thiosulfate (STS)) for the prevention of platinum-induced ototoxicity in pediatric patients, reported that the U.S. Patent and Trademark Office will issue U.S. Patent 10,596,190 entitled "Method for Reducing Ototoxicity in Pediatric Patients Receiving Platinum-Based Chemotherapy (Press release, Fennec Pharmaceuticals, MAR 5, 2020, View Source [SID1234555217])." As suggested by the title, the patent captures the use of Fennec’s PEDMARK product to reduce the ototoxic effects of cisplatin in pediatric patients, particularly in the age group of five years or younger. This is U.S Food and Drug Administration (FDA) Orange Book eligible U.S. patent, and reflects Fennec’s strategy to expand and diversify its intellectual property portfolio to obtain protection for the PEDMARK product.

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

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

                  Schedule Your 30 min Free Demo!

PEDMARK was granted Orphan Drug Designation by the FDA in 2004. This designation, along with the U.S. Patent 10,596,190, strengthens the position of PEDMARK as the potential first and only treatment for the prevention of platinum induced ototoxicity in pediatric patients.

About PEDMARK (Sodium Thiosulfate (STS))

Cisplatin and other platinum compounds are essential chemotherapeutic agents for many pediatric malignancies. Unfortunately, platinum-based therapies can cause ototoxicity, or hearing loss, which is permanent, irreversible and particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe, it is estimated annually that over 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this hearing loss and only expensive, technically difficult and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

PEDMARK has been studied by cooperative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled one of five childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors.

In February 2020, Fennec completed its rolling submission of a New Drug Application (NDA) to the FDA for PEDMARK and submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for sodium thiosulfate (tradename to be determined). PEDMARK received Breakthrough Therapy and Fast Track Designation by the FDA in March 2018. Further, PEDMARK has received Orphan Drug Designation in the U.S. for this setting.

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]).

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

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

                  Schedule Your 30 min Free Demo!

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.

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]).

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

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

                  Schedule Your 30 min Free Demo!

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).

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.

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

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

                  Schedule Your 30 min Free Demo!

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."