VBI Vaccines Presents Early GBM Tumor Response and Immunologic Data from Part B of Ongoing Phase 1/2a Study of VBI-1901 at the 2019 SNO Annual Meeting

On November 22, 2019 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported the presentation of interim data from Part B of the ongoing Phase 1/2a study of VBI-1901, its cancer vaccine immunotherapeutic candidate, in recurrent glioblastoma (GBM) patients in a poster presentation at the 24th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO) (Press release, VBI Vaccines, NOV 22, 2019, View Source [SID1234551615]).

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Though early in the enrollment process for Part B, the tumor and immunologic responses seen thus far have aligned with the responses and benefit observed in Part A of the study. The second patient enrolled in Part B demonstrates sustained stable disease (SD) after four monthly vaccinations of VBI-1901, following a 33% reduction in tumor size after the first vaccination. Among patients evaluable for response and survival in Part A, follow-up analysis showed the 6-month overall survival (OS) to be 100% in vaccine responders (6/6) compared with 63% in vaccine non-responders (5/8). Median OS in the high-dose cohort of Part A, and more broadly among vaccine responders in Part A, have not yet been reached.

"The clinical outcomes from Part A, the tumor responses we’ve seen in three of the six patients in the high-dose cohort in Part A, and now again the tumor response seen in one of the two patients enrolled and evaluable to-date in Part B continue to be encouraging," said David E. Anderson, Ph.D., VBI’s Chief Scientific Officer. "In an effort to better understand these early tumor response data, we are also characterizing baseline biomarkers and immunologic responses, notably T cell responses. Correlations between immunological biomarkers and tumor/clinical responses will be refined as more patients are enrolled in Part B of the study."

To-date, the ongoing Phase 1/2a open-label multicenter study has enrolled all 18 recurrent GBM patients in Part A of the study and four first-recurrent GBM patients in Part B. As of the cut-off date of November 18, 2019, of the four patients enrolled in Part B of the study, two were evaluable for immunologic responses, and one was evaluable for tumor response.

Highlights from Poster Presentation

●Safety:

○VBI-1901 continues to be well-tolerated, with no vaccine-related safety signals observed

●Immunogenicity:
○The first patient enrolled in Part B demonstrated a robust immune response, including a substantial increase in T cells – though the patient continues to be clinically stable, surgical resection and analysis are ongoing to assess status of tumor response
○The second patient enrolled in Part B demonstrated a 33% reduction in tumor size after the first vaccination of VBI-1901 – classification of stable disease (SD) based on two consecutive Magnetic Resonance Imaging (MRI) scans
○In the high-dose cohort of Part A, vaccine response correlated with tumor response, with all three vaccine responders demonstrating SD for greater than 12 weeks – median overall survival in these patients has not yet been reached
○Two patients in the high-dose cohort of Part A experienced a 60% reduction in the size of primary tumor – VBI-1901 also induced and expanded robust T cell responses in these patients
○Correlations between immunologic biomarkers and tumor/clinical responses will be refined as more patients are enrolled in Part B of the study

The poster presentation is available on the "Events/Presentations" page in the "Investors" section of the VBI Vaccines website.

Poster Presentation/Session Details

-Title: Interim Results of the Extension Phase of a Phase I/IIa Trial of a Therapeutic CMV Vaccine Against Recurrent Glioblastoma (GBM)
-Abstract: ATIM-26
-Date: Friday, November 22, 2019
-Time: 7:30PM – 9:30PM MST
-Location: Marriott Desert Ridge Hotel in Phoenix, Arizona, Ballroom Lawn

About the Phase 1/2a Study Design

VBI’s two-part Phase 1/2a study is a multi-center, open-label, dose-escalation study of VBI-1901 in up to 38 patients with recurrent GBM:

Part A:

Dose-escalation phase that defined the safety, tolerability, and optimal dose level of VBI-1901 adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF) in recurrent GBM patients, with any number of prior recurrences.
This phase enrolled 18 recurrent GBM patients across three dose cohorts of VBI-1901: 0.4 µg, 2.0 µg, and 10.0 µg.
Enrollment completed in December 2018
Part B:

Subsequent extension of the optimal dose level, 10.0 µg, as defined in the Part A dose escalation phase.
This phase is a two-arm study, enrolling 10 first-recurrent GBM patients in each arm, assessing 10.0 µg of VBI-1901 in combination with either GM-CSF or AS01B as immunomodulatory adjuvants.
Enrollment of the 10 patients in the GM-CSF arm is ongoing, initiation of enrollment of the 10 patients in the AS01B arm is expected around year-end 2019, subject to FDA acceptance of the amended protocol and investigational site institutional review board approvals.

VBI-1901 is administered intradermally when adjuvanted with GM-CSF and will be administered intramuscularly when adjuvanted with AS01B adjuvant system. Patients in both phases of the study will receive the vaccine immunotherapeutic every four weeks until tumor progression.

Additional information, including a detailed description of the study design, eligibility criteria, and investigator sites, is available at ClinicalTrials.gov using identifier NCT03382977.

Varian Updates GAAP Results for Fourth Quarter and Full Fiscal Year 2019

On November 22, 2019 Varian (NYSE: VAR) reported updates to its previously reported GAAP preliminary financial results for its fourth quarter and full fiscal year 2019 (Press release, Varian Medical Systems, NOV 22, 2019, View Source [SID1234551614]). There is no impact to Non-GAAP financial measures.

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Earlier this week the Company learned new facts and determined that the projected financial performance of its recently acquired Endocare and Alicon businesses was better than previously expected and the mix of revenues is different than previously expected, resulting in an increase in the fair value of the contingent consideration payable under earnout obligations to the sellers of the businesses. This increase in fair value has resulted in an $18.6 million increase in acquisition-related expenses in the fourth quarter of fiscal year 2019 and an $18.6 million increase in accrued liabilities as of the end of the fourth quarter of fiscal year 2019, with corresponding impacts on the company’s previously reported GAAP financial results for the fourth quarter and full fiscal year 2019. The fair value increase has no impact on the company’s previously reported Non-GAAP financial results for the periods.

Updated summary financial statements reflecting the increase in acquisition-related expenses and the increase in accrued liabilities are included below. The updated condensed consolidated financial statements also reflect other balance sheet closing item adjustments, primarily related to the company’s recent acquisition activity.

Entry into a Material Definitive Agreement

On November 22, 2019 Heat Biologics reported that it was awarded $15.2 million to fund preclinical and certain clinical activities from Cancer Prevention Institute of Texas (CPRIT) grant (the "CPRIT Grant") (Filing, 8-K, Heat Biologics, NOV 22, 2019, View Source [SID1234551613]). The CPRIT Grant is subject to customary CPRIT funding conditions.

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The CPRIT Grant initially covered a three-year period from June 1, 2017 through May 31, 2019. On April 12, 2019, CPRIT notified Pelican that it agreed to a six-month extension of time in order to conclude the approved scope of work, such that the completion date was extended from May 31, 2019 to November 30, 2019. On November 20, 2019, CPRIT notified Pelican that it agreed to a six-month extension of time in order to conclude the approved scope of work, such that the completion date was extended from November 30, 2019 to May 30, 2020. All other terms and conditions of the CPRIT arrangement remained the same.

Roche presents pivotal data demonstrating Tecentriq in combination with Avastin improves overall survival in people with the most common form of liver cancer

On November 22, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will present positive results from the Phase III IMbrave150 study evaluating Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) (Press release, Hoffmann-La Roche, NOV 22, 2019, View Source [SID1234551611]). The data show statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS), compared with sorafenib, in people with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

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Tecentriq in combination with Avastin reduced the risk of death (OS) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42–0.79; p=0.0006) and reduced the risk of disease worsening or death (PFS) by 41% (HR=0.59; 95% CI: 0.47–0.76; p<0.0001), compared with sorafenib. Safety for Tecentriq and Avastin was consistent with the known safety profiles of the individual medicines.

"For the first time in a decade, we are seeing a treatment that has improved overall survival for people with unresectable hepatocellular carcinoma compared with the current standard of care," said Levi Garraway, M.D., Ph.D, Chief Medical Officer and Head of Global Product Development. "Tecentriq in combination with Avastin could transform the treatment of this aggressive disease, and we are working closely with global health authorities in the hope of bringing this treatment option to patients as soon as possible."

Over 750,000 people worldwide are diagnosed with HCC, the most common form of liver cancer, every year – with the majority of cases in Asia and almost half of all cases in China. Elsewhere, incidence of liver cancer is on the rise across Europe and the US, with the number of liver cancer cases in the US more than tripling since 1980.

These data will be presented in the Presidential session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress 2019 on 23 November at 11:00 a.m. (Singapore Standard time) (Abstract LBA3).

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMbrave150 study
IMbrave150 is a global Phase III, multicentre, open-label study of 501 people with unresectable HCC who have not received prior systemic therapy. People were randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq was administered intravenously (IV), 1200 mg on day 1 of each 21-day cycle, and Avastin was administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered by mouth, 400 mg twice per day, on days 1–21 of each 21-day cycle. People received the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints were OS and PFS by independent review facility (IRF) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Additional study endpoints included overall response rate (ORR), time to progression (TTP) and duration of response (DoR), as measured by RECIST v1.1 (investigator-assessed [INV] and IRF) and HCC mRECIST (IRF), as well as patient-reported outcomes (including time to deterioration of patient-reported quality of life), safety and pharmacokinetics.

Key efficacy endpoint results for OS and PFS (co-primary endpoints) are below:

NE, not estimable (Median OS for Tecentriq + Avastin not yet reached. For the control arm, the upper CI limit was not estimable); median follow-up 8.6 months; PFS measured as per IRF RECIST v1.1.

Grade 3-4 adverse events (AEs) occurred in 57% of people receiving Tecentriq and Avastin and 55% of people receiving sorafenib. Grade 5 AEs occurred in 5% and 6% of people, respectively.

About hepatocellular carcinoma
HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.1 Over 750,000 people worldwide are diagnosed with HCC every year,1,2 with the majority of cases in Asia and almost half of all cases in China.2,3 In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest rising cause of cancer-related death, while in Europe liver cancer is also on the rise.4,5,6 HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.1 The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.7

About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

Dr. Reddy’s Laboratories announces launch of Doxercalciferol Injection in the U.S. Market

On November 22, 2019 Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, along with its subsidiaries together referred to as "Dr. Reddy’s") reported the launch of Doxercalciferol Injection, 4 mcg/2 mL (2 mcg/mL) Multiple-Dose Vials, the therapeutic generic equivalent of Hectorol (doxercalciferol) Injection 4 mcg/2 mL (2 mcg/mL) Multiple-Dose Vials, approved by the U.S. Food and Drug Administration (USFDA) (Press release, Dr Reddy’s, NOV 22, 2019, View Source [SID1234551610]).

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The Hectorol Injection 4 mcg/2 mL (2 mcg/mL) Single-Dose Vials and Multiple-Dose Vials brand and generics had U.S. sales of approximately $138 million MAT for the most recent twelve months ending in September 2019 according to IQVIA Health*.

Hectorol is a trademark of Sanofi-Aventis US LLC.

*IQIA Retail and Non-Retail MAT September 2019

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