The trial aims to collect safety, efficacy, exposure, dose- response, pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels in patients with Glioblastoma at progression or recurrence

Start Date01 Jun 2024

Sponsor / Collaborator

Philogen SpA

NCT06419946 / Not yet recruitingPhase 3IIT

Phase III Trial of Temozolomide/Lomustine (TMZ/LOM) Combination Therapy vs. Standard TMZ Therapy for Newly Diagnosed MGMT Promoter Methylated Glioblastoma (IDHwt) Patients +/- Tumor Treating Fields (Optune)

Background: Glioblastoma (GBM) is notoriously difficult to treat, with current therapies often extending life by only a few months. The standard treatment involves surgery followed by radiation and chemotherapy with Temozolomide (TMZ). The efficacy of TMZ, however, is significantly enhanced when the tumor's o6-methylguanine-DNA-methyltransferase (MGMT) gene is methylated. Recent studies, such as the NOA-09 trial, have suggested that adding Lomustine (LOM) to TMZ could improve outcomes for patients with this specific tumor profile.
Hypothesis: The investigators hypothesize that the addition of LOM to the TMZ regimen will lead to significantly improved survival rates among patients with newly diagnosed glioblastoma who have a methylated MGMT promoter compared to those receiving only TMZ.
Treatment Plans: The study will randomly assign participants to two groups:
Control Group: Standard treatment with TMZ during and after radiation therapy.
Experimental Group: TMZ combined with LOM, starting on the first day of radiation therapy.
Outcome Measures: The primary outcome measure will be survival. Other outcomes will include progression-free survival (time from randomization until tumor progression or death), safety profiles (adverse effects of the treatments), and quality of life measures as well as neurocognitive outcomes.

Start Date15 May 2024

Sponsor / Collaborator

Region Västra Götaland

[+12]

NCT05904119 / RecruitingPhase 3

Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study

Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Treatment options include repeated surgery (if feasible), systemic therapy (bevacizumab, lomustine, temozolomide re-challenge), reirradiation and best supportive care. Currently, the superiority of combined chemoradiation versus chemotherapy alone remains unproven. Given that lomustine is the standard chemotherapeutic agent for the treatment of recurrent glioblastoma in Europe and the unclear efficacy of reirradiation, we want to explore whether combining lomustine and reirradiation may be a better treatment than lomustine alone. The results of the prospective randomized trial proposed here should demonstrate a significant improvement in overall survival when lomustine is combined with reirradiation in patients with recurrent glioblastoma compared to lomustine alone without adversely affecting quality of survival. The trial will be stopped based on overall survival in a preplanned futility and efficacy interim analysis.

Start Date15 Mar 2024

Sponsor / Collaborator

Eortc

100 Clinical Results associated with Lomustine

100 Translational Medicine associated with Lomustine

100 Patents (Medical) associated with Lomustine

2,646

Literatures (Medical) associated with Lomustine

01 Jan 2024·Pediatric blood & cancer

Pediatric glioblastoma in the setting of constitutional mismatch‐repair deficiency treated with upfront lomustine and nivolumab

Author: Hidalgo, E Teresa ; Snuderl, Matija ; Radmanesh, Ali ; Cantor, Anna ; Cooper, Benjamin ; Nicolaides, Theodore ; Zan, Elcin ; Krugman, Jessica ; Patel, Krupesh

01 Jan 2024·Phytomedicine : international journal of phytotherapy and phytopharmacology

Artesunate in glioblastoma therapy: Case reports and review of clinical studies

Article

Author: Kaina, Bernd ; Strik, Herwig ; Efferth, Thomas

BACKGROUND:

Artesunate, a derivative of the active ingredient artemisinin from Artemisia annua L. used for centuries in the traditional Chinese medicine, is being applied as front-line drug in malaria treatment. As it is cytotoxic for cancer cells, trials are ongoing to include this drug as supplement in cancer therapy. In glioblastoma cells, artesunate was shown to induce oxidative stress, DNA base damage and double-strand breaks (DSBs), apoptosis, and necroptosis. It also inhibits DNA repair functions and bears senolytic activity. Compared to ionizing radiation, DNA damages accumulate over the whole exposure period, which makes the agent unique in its genotoxic profile. Artesunate has been used in adjuvant therapy of various cancers.

PURPOSE:

As artesunate has been used in adjuvant therapy of different types of cancer and clinical trials are lacking in brain cancer, we investigated its activity in glioma patients with focus on possible side effects.

STUDY DESIGN:

Between 2014 and 2020, twelve patients were treated with artesunate for relapsing glioma and analyzed retrospectively: 8 males and 4 females, median age 45 years.

HISTOLOGY:

4 glioblastomas WHO grade 4, 5 astrocytomas WHO grade 3, 3 oligodendrogliomas grade 2 or 3. All patients were pretreated with radiation and temozolomide-based chemotherapy. Artesunate 100 mg was applied twice daily p.o. combined with dose-dense temozolomide alone (100 mg/m² day 1-5/7, 10 patients) or with temozolomide (50 mg/m² day 1-5/7) plus lomustine (CCNU, 40 mg day 6/7). Blood count, C-reactive protein (CRP), liver enzymes, and renal parameters were monitored weekly.

RESULTS:

Apart from one transient grade 3 hematological toxicity, artesunate was well tolerated. No liver toxicity was observed. While 8 patients with late stage of the disease had a median survival of 5 months after initiation of artesunate treatment, 4 patients with treatment for remission maintenance showed a median survival of 46 months. We also review clinical trials that have been performed in other cancers where artesunate was included in the treatment regimen.

CONCLUSIONS:

Artesunate administered at a dose of 2 × 100 mg/day was without harmful side effects, even if combined with alkylating agents used in glioma therapy. Thus, the phytochemical, which is also utilized as food supplement, is an interesting, well tolerated supportive agent useful for long-term maintenance treatment. Being itself cytotoxic on glioblastoma cells and enhancing the cytotoxicity of temozolomide as well as in view of its senolytic activity, artesunate has clearly a potential to enhance the efficacy of malignant brain cancer therapy.

01 Jan 2024·Yonsei medical journal

High Radiation Dose to the Fornix Causes Symptomatic Radiation Necrosis in Patients with Anaplastic Oligodendroglioma

Article

Author: Yoon, Hong In ; Kim, Tae Hyung ; Chang, Jong Hee ; Moon, Ju Hyung ; Kang, Seok-Gu ; Cho, Jaeho ; Suh, Chang-Ok ; Park, Yae Won

PURPOSE:

Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN).

MATERIALS AND METHODS:

A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed.

RESULTS:

The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, p=0.005).

CONCLUSION:

The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed.

News (Medical) associated with Lomustine

29 May 2024

·www.biospace.com

VBI Vaccines Announces New Tumor Response Data from Ongoing Randomized Controlled Phase 2b Study of VBI-1901 in Recurrent Glioblastoma Patients

Among the 7 patients on VBI-1901 treatment long enough to have 1+ MRI scan at the time of analysis, one partial tumor response (PR) and two stable disease (SD) observations have occurred as of May 15, 2024 The partial response, which demonstrated a 67% reduction in tumor size vs. baseline, was observed at week 6, after 2 doses of VBI-1901 The disease control rate (DCR) in the VBI-1901 study arm was 43% (n=3/7) compared to 0% in the control arm (n=0/6) – n=5/6 patients in the control arm have experienced a 2-8x increase in tumor size vs. baseline and have been taken off study protocol FDA has granted both Fast Track Designation and Orphan Drug Designation to VBI-1901 in recurrent GBM following previous Phase 1/2a study results Additional interim data expected Q4 2024, including additional tumor response data and initial survival data from early-enrolled participants, subject to speed of enrollment CAMBRIDGE, Mass.--(BUSINESS WIRE)-- VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, today announced new interim tumor response data from the ongoing randomized, controlled Phase 2b study of VBI-1901, the Company’s immunotherapeutic cancer vaccine candidate, in recurrent glioblastoma (rGBM) patients. These data will be presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on Saturday, June 1, 2024. David E. Anderson, Ph.D., VBI’s Chief Scientific Officer, said: “The tumor responses we have seen to date are incredibly encouraging, and, like the tumor responses did in the Phase 1/2a study, I am excited to see how this translates to clinical and survival outcomes later this year. The approved treatments for recurrent GBM patients have limited to no efficacy, which is consistent with the data seen in the standard-of-care arm in this study. VBI-1901’s ability to stimulate an immune response capable of generating a disease control rate of 43% at this interim stage of the study, including a partial response, is hopefully an indication of the potential of this candidate to make a meaningful difference in the lives of patients, providers, and families.” Jeff Baxter, VBI’s President and CEO, said: “These data represent a considerable advancement in our effort to make a difference in the fight against GBM. Throughout the remainder of 2024, we expect to have additional tumor response data and initial survival data. Pending the strength of these clinical data, we believe we can start discussions with the FDA around what an accelerated development and approval pathway looks like, under our Fast Track and Orphan Drug Designations.” Phase 2b Data Poster Highlights As of May 15, 2024, 23 patients had been randomized 1:1 to either the active treatment arm, VBI-1901, or to the control treatment arm (standard-of-care). Active Study Arm: VBI-1901 + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 11 patients have been randomized – tumor response data was available for 7 of those patients as of May 15, 2024 One (1) PR and two (2) SD observations seen to date The patient with the PR saw a 67% tumor reduction compared to baseline at week 6, after receiving two monthly doses of VBI-1901 43% (n=3/7) disease control rate achieved in evaluable patients to date 2 additional patients appear to be experiencing stabilization of tumor growth after their second dose of VBI-1901, but do not yet meet the threshold to qualify as stable disease Control Study Arm: Standard-of-Care (SoC) Therapy – Carmustine or Lomustine 12 patients have been randomized – tumor response data was available for 6 of those patients as of May 15, 2024 No tumor responses have been observed in the SoC arm (n=0/6; 0% DCR) 5 evaluable patients have experienced tumor progression of 2-8x increase in tumor size and have been taken off study protocol Tumor response rates are an objective measure of treatment efficacy in oncology trials. In VBI’s previous Phase 1/2a study of VBI-1901 in rGBM, a 44% disease control rate was observed (n=7/16), which translated to clinical improvements in overall survival, with a median overall survival (mOS) of 12.9 months after treatment with VBI-1901 compared to the 8-month mOS historical benchmark for standard-of-care chemotherapy treatment. ASCO Poster Details Title: Randomized Phase 2b trial of a CMV vaccine immunotherapeutic candidate (VBI-1901) in recurrent glioblastomas Abstract Number: TPS2100 Date & Time: 9:00 AM – 12:00 PM CDT, Saturday, June 1, 2024 Poster Session: Central Nervous System Tumors VBI’s poster presentation will be made available on the Posters page of VBI’s website, under News and Resources, after the Central Nervous System Tumors poster session concludes on June 1, 2024. Phase 2b Patient Enrollment Update 26 patients have been randomized as of May 28, 2024 Patient enrollment rate continues to increase, with six (6) patients randomized in May VBI expects the study to be fully enrolled (n=60) by year-end 2024, subject to continued pace of enrollment Phase 2b Study Design Multi-center, randomized, controlled, open-label study in up to 60 patients with first recurrent GBM Patients will be randomized in a 1:1 ratio across two study arms: Intradermal VBI-1901 + GM-CSF: 10 µg dose every 4 weeks until clinical disease progression Monotherapy standard-of-care: either intravenous carmustine or oral lomustine, every 6 weeks until disease progression or intolerable toxicity Endpoints include: Safety and tolerability Overall survival (OS) – median and overall Tumor response rate (TRR) Progression-free survival (PFS) Immunologic responses Reduction in corticosteroid use relative to baseline Change in quality of life compared to baseline The randomized, controlled Phase 2b study is evaluating overall survival, tumor response rates, and safety and tolerability of VBI-1901 as a monotherapy treatment in rGBM patients. There are no effective, approved treatments available for patients with rGBM, and median overall survival remains low at approximately eight (8) months. The U.S. Food and Drug Administration (FDA) has considered demonstration of a statistically significant improvement in overall survival relative to a randomized control arm to be clinically significant and has recognized this as criteria to support the approval of new oncology drugs.1 For more information about the Phase 2b study, visit clinicaltrials.gov and reference trial identifier: NCT03382977. Phase 1/2a Study Data Highlights – VBI-1901 10µg + GM-CSF Study Arms (n=16) 44% disease control rate achieved (n=7/16) – disease control rate is defined as stable disease (SD) + partial tumor response (PR) + complete tumor response (CR) 2 partial responses (PR) were observed – 1 patient was on treatment for more than 28 months (2.33 years), surviving at least 40 months (3.33 years) as of August 1, 2023, with a maximum tumor reduction of 93% relative to baseline 5 additional patients demonstrated stable disease (SD) for a sustained period of time All patients with a tumor response (PR or SD) (n=7/16) reached a minimum survival of 12 months Median overall survival (mOS) was 12.9 months, comparing favorably to 8-month mOS for monotherapy standard-of-care2 About GBM and VBI-1901 Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and has a high mortality. VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI’s enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. The FDA has granted VBI-1901 Fast Track Designation and Orphan Drug Designation for the treatment of recurrent glioblastoma. These designations are intended to provide certain benefits to drug developers, including more frequent meetings with the FDA, and Accelerated Approval and Priority Review, if relevant criteria are met, among other benefits. About VBI Vaccines Inc. VBI Vaccines Inc. (“VBI”) is a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease. Through its innovative approach to virus-like particles (“VLPs”), including a proprietary enveloped VLP (“eVLP”) platform technology and a proprietary mRNA-launched eVLP (“MLE”) platform technology, VBI develops vaccine candidates that mimic the natural presentation of viruses, designed to elicit the innate power of the human immune system. VBI is committed to targeting and overcoming significant infectious diseases, including hepatitis B, coronaviruses, and cytomegalovirus (CMV), as well as aggressive cancers including glioblastoma (GBM). VBI is headquartered in Cambridge, Massachusetts, with research operations in Ottawa, Canada, and a research and manufacturing site in Rehovot, Israel. Website Home: News and Resources: Investors: References Oncology Center of Excellence, Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration. Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics; Guidance for Industry. FDA.gov. December, 2018 Taal W, Oosterkamp HM, Walenkamp AME, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomized controlled phase 2 trial. Lancet Oncol. 2014; 15: 943-953 Cautionary Statement on Forward-looking Information Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). The Company cautions that such forward-looking statements involve risks and uncertainties that may materially affect the Company’s results of operations. Such forward-looking statements are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including but not limited to, the Company’s ability to regain and maintain compliance with the listing standards of the Nasdaq Capital Market, the Company’s ability to satisfy all of the conditions to the consummation of the transactions with Brii Biosciences, the Company’s ability to comply with its obligations under its loan agreement with K2 HealthVentures, the impact of general economic, industry or political conditions in the United States or internationally; the impact and continuing effects of the COVID-19 epidemic on our clinical studies, manufacturing, business plan, and the global economy; the ability to successfully manufacture and commercialize PreHevbrio/PreHevbri; the ability to establish that potential products are efficacious or safe in preclinical or clinical trials; the ability to establish or maintain collaborations on the development of pipeline candidates and the commercialization of PreHevbrio/PreHevbri; the ability to obtain appropriate or necessary regulatory approvals to market potential products; the ability to obtain future funding for developmental products and working capital and to obtain such funding on commercially reasonable terms; the Company’s ability to manufacture product candidates on a commercial scale or in collaborations with third parties; changes in the size and nature of competitors; the ability to retain key executives and scientists; and the ability to secure and enforce legal rights related to the Company’s products. A discussion of these and other factors, including risks and uncertainties with respect to the Company, is set forth in the Company’s filings with the SEC and the Canadian securities authorities, including its Annual Report on Form 10-K filed with the SEC on April 16, 2024, and filed with the Canadian security authorities at sedarplus.ca on April 16, 2024, as may be supplemented or amended by the Company’s Quarterly Reports on Form 10-Q. Given these risks, uncertainties and factors, you are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement. All such forward-looking statements made herein are based on our current expectations and we undertake no duty or obligation to update or revise any forward-looking statements for any reason, except as required by law.

Clinical ResultFast TrackPhase 2ASCOVaccine

22 May 2024

·www.biospace.com

VBI Vaccines Announces Poster Presentation at 2024 ASCO Annual Meeting Highlighting New Interim Phase 2b Data from VBI-1901 in Recurrent Glioblastoma Patients

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, today announced that new interim tumor response data from the ongoing randomized, controlled Phase 2b study of VBI-1901, the Company’s cancer vaccine immunotherapeutic candidate in recurrent glioblastoma (GBM), were accepted for poster presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The presentation at ASCO will provide an update to the encouraging data previously shared at the World Vaccine Congress Washington in April, including additional data from those initially evaluable patients, as well as data from new patients who have since been randomized into the Phase 2b study. Presentation Details Title: Randomized Phase 2b trial of a CMV vaccine immunotherapeutic candidate (VBI-1901) in recurrent glioblastomas Date: Saturday, June 1, 2024 Poster Session: Central Nervous System Tumors Poster Session Time: 9:00 AM – 12:00 PM CDT Phase 2b Study Design Multi-center, randomized, controlled, open-label study in up to 60 patients with first recurrent GBM Patients will be randomized in a 1:1 ratio across two study arms: Intradermal VBI-1901 + GM-CSF: 10 µg dose every 4 weeks until clinical disease progression Monotherapy standard-of-care: either intravenous carmustine or oral lomustine, every 6 weeks until disease progression or intolerable toxicity Endpoints include: Safety and tolerability Overall survival (OS) – median and overall Tumor response rate (TRR) Progression-free survival (PFS) Immunologic responses Reduction in corticosteroid use relative to baseline Change in quality of life compared to baseline The U.S. Food and Drug Administration (FDA) has considered demonstration of a statistically significant improvement in overall survival relative to a randomized control arm to be clinically significant and has recognized this as criteria to support the approval of new oncology drugs.1 For more information about the Phase 2b study, visit clinicaltrials.gov and reference trial identifier: NCT03382977. About GBM and VBI-1901 Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, more than 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and has a high mortality. VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI’s enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. The FDA has granted VBI-1901 Fast Track Designation and Orphan Drug Designation for the treatment of recurrent glioblastoma. These designations are intended to provide certain benefits to drug developers, including more frequent meetings with the FDA, and Accelerated Approval and Priority Review, if relevant criteria are met, among other benefits. About VBI Vaccines Inc. VBI Vaccines Inc. (“VBI”) is a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease. Through its innovative approach to virus-like particles (“VLPs”), including a proprietary enveloped VLP (“eVLP”) platform technology and a proprietary mRNA-launched eVLP (“MLE”) platform technology, VBI develops vaccine candidates that mimic the natural presentation of viruses, designed to elicit the innate power of the human immune system. VBI is committed to targeting and overcoming significant infectious diseases, including hepatitis B, coronaviruses, and cytomegalovirus (CMV), as well as aggressive cancers including glioblastoma (GBM). VBI is headquartered in Cambridge, Massachusetts, with research operations in Ottawa, Canada, and a research and manufacturing site in Rehovot, Israel. Website Home: News and Resources: Investors: References: 1. Oncology Center of Excellence, Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration. Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics; Guidance for Industry. FDA.gov. December, 2018 Cautionary Statement on Forward-looking Information Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). The Company cautions that such forward-looking statements involve risks and uncertainties that may materially affect the Company’s results of operations. Such forward-looking statements are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including but not limited to, the Company’s ability to regain and maintain compliance with the listing standards of the Nasdaq Capital Market, the Company’s ability to satisfy all of the conditions to the consummation of the transactions with Brii Biosciences, the Company’s ability to comply with its obligations under its loan agreement with K2 HealthVentures, the impact of general economic, industry or political conditions in the United States or internationally; the impact of the COVID-19 endemic on our clinical studies, manufacturing, business plan, and the global economy; the ability to successfully manufacture and commercialize PreHevbrio/PreHevbri; the ability to establish that potential products are efficacious or safe in preclinical or clinical trials; the ability to establish or maintain collaborations on the development of pipeline candidates and the commercialization of PreHevbrio/PreHevbri; the ability to obtain appropriate or necessary regulatory approvals to market potential products; the ability to obtain future funding for developmental products and working capital and to obtain such funding on commercially reasonable terms; the Company’s ability to manufacture product candidates on a commercial scale or in collaborations with third parties; changes in the size and nature of competitors; the ability to retain key executives and scientists; and the ability to secure and enforce legal rights related to the Company’s products. A discussion of these and other factors, including risks and uncertainties with respect to the Company, is set forth in the Company’s filings with the SEC and the Canadian securities authorities, including its Annual Report on Form 10-K filed with the SEC on April 16, 2024, and filed with the Canadian security authorities at sedarplus.ca on April 16, 2024, as may be supplemented or amended by the Company’s Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Given these risks, uncertainties and factors, you are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement. All such forward-looking statements made herein are based on our current expectations and we undertake no duty or obligation to update or revise any forward-looking statements for any reason, except as required by law.

Fast TrackPhase 2ASCOVaccineImmunotherapy

15 May 2024

·www.biospace.com

VBI Vaccines Reports First Quarter 2024 Financial Results

PreHevbrio® (Hepatitis B Vaccine [Recombinant]) global net revenue increased 105% year-over-year in the first quarter of 2024 compared to the first quarter of 2023 Initial encouraging tumor response data from randomized Phase 2b study of VBI-1901 in recurrent glioblastoma (GBM) announced in April – additional data expected mid-year and year-end 2024 Evaluation of novel mRNA-launched eVLP (MLE) platform technology underway by potential partners CAMBRIDGE, Mass.--(BUSINESS WIRE)-- VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, today provided a business update and announced financial results for the quarter ended March 31, 2024. “To date in 2024, our focus has centered around pipeline execution, expanding access and increased uptake of PreHevbrio in targeted market segments, and execution of strategic partnerships to drive opportunity for our portfolio assets, create shareholder value, and strengthen our balance sheet,” said Jeff Baxter, VBI’s President and CEO. “We remain committed to creating opportunities for our vaccines, candidates, and technologies to meaningfully impact public health and the lives of patients, providers, and families.” Recent Key Program Achievements and Projected Upcoming Milestones PreHevbrio® [Hepatitis B Vaccine (Recombinant)] Product revenue, net increased 105% from Q1 2023, with $1.0 million earned in Q1 2024 US: H1 2024 PreHevbrio U.S. sales continue to demonstrate substantial growth over 2023, with over 80% of the 2023 full-year volume being sold in the first five months of 2024 Commercial execution in Q1 2024 created new demand in the large Integrated Delivery Network (IDN) and hospital system space, and saw continued national and regional pharmacy uptake Public sector momentum building with PreHevbrio now available for purchase under the CDC Adult Vaccine Contract Ex-US – PreHevbri®: VBI partners with Valneva SE to make PreHevbri available in certain European countries In 2023, through this partnership, PreHevbri was launched in the UK, Sweden, Netherlands, and Belgium – in early 2024, PreHevbri also became available in Denmark and Norway VBI-1901: Cancer Vaccine Immunotherapeutic Candidate – Glioblastoma (GBM) VBI-1901 is being evaluated in an ongoing, randomized, controlled Phase 2b study in comparison to standard-of-care chemotherapy treatment in recurrent GBM patients April 2024: Encouraging early tumor response data from Phase 2b study in recurrent GBM presented at World Vaccine Congress 2024: VBI-1901 Arm: 2 stable disease (SD) observations among patients eligible for evaluation at week 12 (n=2/5), achieving a 40% disease control rate, consistent with 44% disease control rate observed in the Phase 1/2a portion of the study Control Arm (carmustine or lomustine chemotherapy): No tumor responses have been observed to date (n=0/6; 0% disease control rate) – all evaluable patients experienced a 2-8x increase in tumor size by week 6 and have been taken off study protocol Mid-Year 2024 and Year-End: Additional tumor response data from ongoing Phase 2b study expected mid-year 2024, with initial survival data from early-enrolled participants expected by year-end 2024, subject to speed of enrollment Novel mRNA-Launched eVLP (MLE) Technology Platform April 2024: Announced expansion of strategic partnership with the Canadian Government to advance the development of the MLE technology platform, supported by the CAD$28 million funding award remaining under the original agreement Throughout 2024: MLE technology remains under active evaluation by potential partners Other Achievements and Upcoming Milestones February 2024: Announced a series of agreements with Brii Biosciences (“Brii Bio”), pursuant to which, subject to achievement of certain activities, VBI would receive up to $33 million in consideration for VBI’s manufacturing capabilities and certain related assets at Rehovot manufacturing facility, the intellectual property for VBI-2601, VBI’s hepatitis B immunotherapeutic candidate, and a license for VBI-1901 in the Asia Pacific region, excluding Japan Following completion of the full transaction, target mid-year 2024, VBI expects its total debt principal to be significantly reduced to $17 million 2024: Additional data expected from Phase 1 study of VBI-2901, VBI’s multivalent pan-coronavirus vaccine candidate – initial data from which were reported in September 2023 Recent Peer-Reviewed Publications Langley, Gantt, et al., “An enveloped virus-like particle alum-adjuvanted cytomegalovirus vaccine is safe and immunogenic: A first-in-humans Canadian Immunization Research Network (CIRN) study” published in Vaccine – Link Here Financial Results for the Three Months Ended March 2024 Cash Position: As of March 31, 2024 VBI had $12.6 million in cash as compared with $23.7 million in cash as of December 31, 2023. Cash position at March 31, 2024, does not include approximately $2.8 million gross proceeds from registered direct offering of common shares and warrants, warrant exercises, and sale of common shares through VBI’s at-the-market facility with Jefferies LLC, subsequent to March 31, 2024 and through early April 2024. Revenues, net: Revenues, net for the first quarter 2024 were $1.2 million as compared to $0.5 million for the same period in 2023. The revenue increase was a result of an increase in product sales of PreHevbrio in the U.S. Cost of Revenues: Cost of revenues was $2.7 million in the first quarter of 2024 as compared to $3.6 million in the first quarter of 2023. The decrease in the cost of revenues was a result of the April 2023 organizational changes and decreased inventory-related costs, offset by increased product sales. Research and Development (R&D): R&D expenses for the first quarter of 2024 were $2.6 million as compared to $3.2 million for the same period in 2023. R&D expenses were offset by $0.7 million for the three months ended March 31, 2024, and $2.4 million for the three months ended March 31, 2023 due to government grants and funding arrangements. The decrease in R&D expenses is primarily a result of decreased development expenses for VBI’s pan-coronavirus and GBM candidates, VBI-2901 and VBI-1901, due to timing of ongoing clinical studies of each candidate. Sales, General, and Administrative (SG&A): SG&A expenses for the first quarter of 2024 were $7.7 million as compared to $13.3 million in the first quarter of 2023. The decrease in SG&A expenses was mainly a result of the April 2023 organizational changes that reduced our internal workforce, commercial field teams, and operating expenses. Net Cash Used in Operating Activities: Net cash used in operating activities for the first quarter of 2024 was $11.8 million compared to $21.7 million for the same period in 2023. The 46% decrease in cash outflows is largely due to a decrease in net loss as a result of the April 2023 organizational changes, in addition to the change in operating working capital, most notably in inventory, other current assets, accounts payable, and other current liabilities. Net Loss and Net Loss Per Share: Net loss and net loss per share for the first quarter of 2024 were $17.9 million and $0.73, respectively, as compared to a net loss and net loss per share of $27.8 million and $3.22 for the first quarter of 2023, respectively. Net Loss and Net Loss Per Share, Excluding Foreign Exchange Loss: Net loss and net loss per share, excluding foreign exchange loss, for the first quarter 2024 were $13.6 million and $0.55, respectively, compared to $20.9 million and $2.43 for the first quarter 2023, respectively. See “Use of Non-GAAP Financial Measures” below for additional information regarding this non-GAAP financial measure, and “GAAP to Non-GAAP Reconciliation” for a reconciliation of this non-GAAP financial measure to net loss and net loss per share. Foreign exchange loss for the first quarter of 2024 was $4.3 million as compared to $6.8 million for the first quarter of 2023. Certain intercompany loans between the Company and its subsidiaries are denominated in a currency other than the functional currency of each entity. The decrease in foreign exchange loss was a result of the changes in the foreign currency exchange rates (of the New Israeli Shekel and the Canadian Dollar) in which the foreign currency transactions were denominated for each of those periods, including the foreign exchange impact of intercompany loans that are translated at period end. Use of Non-GAAP Financial Measures Net Loss, Excluding Foreign Exchange Loss, and Net Loss Per Share, Excluding Foreign Exchange Loss, are non-GAAP financial measures and are defined as Net Loss and Net Loss Per Share excluding the foreign exchange loss in both calculations. Net Loss, Excluding Foreign Exchange Loss, and Net Loss Per Share, Excluding Foreign Exchange Loss, are not intended to replace Net Loss or Net Loss Per Share or other measures of financial performance reported in accordance with generally accepted accounting principles (GAAP). VBI’s management believes that the presentation of Net Loss, Excluding Foreign Exchange Loss, and Net Loss Per Share, Excluding Foreign Exchange Loss, are useful to investors because management does not consider foreign exchange loss, which is primarily driven by changes in exchange rates related to certain intercompany loans, and is a non-recurring item, when evaluating VBI’s operating performance. Non-GAAP financial measures are meant to supplement, and to be viewed in conjunction with, GAAP financial results. The presentation of these non-GAAP financial measures should not be considered in isolation or as a substitute for comparable GAAP financial measures and should be read only in conjunction with the Company’s financial statements prepared in accordance with GAAP. Reconciliations of the Company’s non-GAAP measures are included below. The following represents a reconciliation of Net Loss to Net Loss, Excluding Foreign Exchange Loss, and Net Loss Per Share to Net Loss Per Share, Excluding Foreign Exchange Loss. See “Non-GAAP Financial Information” below for additional information regarding this non-GAAP financial measure, and “GAAP to Non-GAAP Reconciliation” for a reconciliation of this non-GAAP financial measure to net loss and net loss per share. GAAP to Non-GAAP Reconciliations The following represents a reconciliation of Net Loss to Net Loss Excluding Impairment Charges and Foreign Exchange Loss and Net Loss per Share Excluding Foreign Exchange Loss. Three Months Ended March 31 2024 2023 (Unaudited) (In 000’s except share and per share amounts) Net Loss $ (17,900 ) $ (27,751 ) Foreign exchange loss 4,330 6,813 Net loss, excluding impairment charges and foreign exchange loss $ (13,570 ) $ (20,938 ) Weighted-average number of shares 24,584,798 8,608,539 Net loss per share, excluding impairment charges and foreign exchange loss $ (0.55 ) $ (2.43 ) About PreHevbrio [Hepatitis B Vaccine (Recombinant)] PreHevbrio is the only 3-antigen hepatitis B vaccine, comprised of the three surface antigens of the hepatitis B virus – Pre-S1, Pre-S2, and S. It is approved for use in the U.S., European Union/European Economic Area, United Kingdom, Canada, and Israel. The brand names for this vaccine are: PreHevbrio® (US/Canada), PreHevbri® (EU/EEA/UK), and Sci-B-Vac® (Israel). Please visit for U.S. Important Safety Information for PreHevbrio [Hepatitis B Vaccine (Recombinant)], or please see U.S. Full Prescribing Information. U.S. Indication PreHevbrio is indicated for prevention of infection caused by all known subtypes of hepatitis B virus. PreHevbrio is approved for use in adults 18 years of age and older. U.S. Important Safety Information (ISI) Do not administer PreHevbrio to individuals with a history of severe allergic reaction (e.g. anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of PreHevbrio. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of PreHevbrio. Immunocompromised persons, including those on immunosuppressant therapy, may have a diminished immune response to PreHevbrio. PreHevbrio may not prevent hepatitis B infection, which has a long incubation period, in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration. The most common side effects (> 10%) in adults age 18-44, adults age 45-64, and adults age 65+ were pain and tenderness at the injection site, myalgia, fatigue, and headache. There is a pregnancy exposure registry that monitors pregnancy outcomes in women who received PreHevbrio during pregnancy. Women who receive PreHevbrio during pregnancy are encouraged to contact 1-888-421-8808 (toll-free). To report SUSPECTED ADVERSE REACTIONS, contact VBI Vaccines at 1-888-421-8808 (toll-free) or VAERS at 1-800-822-7967 or . Please see Full Prescribing Information. About VBI Vaccines Inc. VBI Vaccines Inc. (“VBI”) is a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease. Through its innovative approach to virus-like particles (“VLPs”), including a proprietary enveloped VLP (“eVLP”) platform technology and a proprietary mRNA-launched eVLP (“MLE”) platform technology, VBI develops vaccine candidates that mimic the natural presentation of viruses, designed to elicit the innate power of the human immune system. VBI is committed to targeting and overcoming significant infectious diseases, including hepatitis B, coronaviruses, and cytomegalovirus (CMV), as well as aggressive cancers including glioblastoma (GBM). VBI is headquartered in Cambridge, Massachusetts, with research operations in Ottawa, Canada, and a research and manufacturing site in Rehovot, Israel. Website Home: News and Resources: Investors: Cautionary Statement on Forward-looking Information Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). The Company cautions that such forward-looking statements involve risks and uncertainties that may materially affect the Company’s results of operations. Such forward-looking statements are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including but not limited to, the Company’s ability to regain and maintain compliance with the listing standards of the Nasdaq Capital Market, the Company’s ability to satisfy all of the conditions to the consummation of the transactions with Brii Biosciences, the Company’s ability to comply with its obligations under its loan agreement with K2 HealthVentures, the impact of general economic, industry or political conditions in the United States or internationally; the impact of the COVID-19 endemic on our clinical studies, manufacturing, business plan, and the global economy; the ability to successfully manufacture and commercialize PreHevbrio/PreHevbri; the ability to establish that potential products are efficacious or safe in preclinical or clinical trials; the ability to establish or maintain collaborations on the development of pipeline candidates and the commercialization of PreHevbrio/PreHevbri; the ability to obtain appropriate or necessary regulatory approvals to market potential products; the ability to obtain future funding for developmental products and working capital and to obtain such funding on commercially reasonable terms; the Company’s ability to manufacture product candidates on a commercial scale or in collaborations with third parties; changes in the size and nature of competitors; the ability to retain key executives and scientists; and the ability to secure and enforce legal rights related to the Company’s products. A discussion of these and other factors, including risks and uncertainties with respect to the Company, is set forth in the Company’s filings with the SEC and the Canadian securities authorities, including its Annual Report on Form 10-K filed with the SEC on April 16, 2024, and filed with the Canadian security authorities at sedarplus.ca on April 16, 2024, as may be supplemented or amended by the Company’s Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Given these risks, uncertainties and factors, you are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement. All such forward-looking statements made herein are based on our current expectations and we undertake no duty or obligation to update or revise any forward-looking statements for any reason, except as required by law. VBI Vaccines Inc. and Subsidiaries Selected Condensed Consolidated Balance Sheet (Unaudited, In Thousands) Three Months Ended March 31 2024 2023 (Unaudited) (In 000’s except share and per share amounts) Assets Cash $ 12,595 $ 23,685 Accounts receivable, net 227 - Inventory, net 9,944 8,499 Prepaid expenses and other current assets 3,595 4,047 Total current assets 26,361 36,231 Property and equipment, net 9,088 9,665 Intangible assets, net 35,734 36,499 Goodwill 1,107 1,130 Other non-current assets 3,153 3,426 Total Assets $ 75,443 $ 86,951 Liabilities and stockholders’ equity Accounts payable $ 8,871 $ 6,431 Other current liabilities 68,723 69,305 Total current liabilities 77,594 75,736 Total non-current liabilities 3,316 3,688 Total liabilities 80,910 79,424 Total stockholders' equity (5,467 ) 7,527 Total liabilities and stockholders' equity $ 75,443 $ 86,951 VBI Vaccines Inc. and Subsidiaries Condensed Consolidated Statement of Operations and Comprehensive Loss (Unaudited, In Thousands Except Share and Per Share Amounts) Three Months Ended March 31 2024 2023 (Unaudited) Revenues, net $ 1,214 $ 485 Operating expenses Cost of revenues 2,724 3,559 Research and development 2,571 3,151 Sales, general, and administrative 7,671 13,284 Total operating expenses 12,966 19,994 Loss from operations (11,752 ) (19,509 ) Interest expense, net of interest income (1,818 ) (1,429 ) Foreign exchange loss (4,330 ) (6,813 ) Loss before income taxes (17,900 ) (27,751 ) Income tax benefit - - Net Loss $ (17,900 ) $ (27,751 ) Basic and diluted net loss per share $ (0.73 ) $ (3.22 ) Weighted-average number of shares used to compute basic and diluted net loss per share 24,584,798 8,608,539 Other comprehensive income 3,484 6,599 Comprehensive Loss $ (14,416 ) $ (21,152 )

VaccineClinical ResultPhase 2Drug ApprovalFinancial Statement

100 Deals associated with Lomustine

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KEGG	Wiki	ATC	Drug Bank
D00363	Lomustine	L01AD02	DB01206

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Bronchogenic Carcinoma	CN	Nanjing Pharmaceutical Factory	01 Jan 1982
Glioma	CN	Nanjing Pharmaceutical Factory	01 Jan 1982
Lymphoma	CN	Nanjing Pharmaceutical Factory	01 Jan 1982
Rectal Cancer	CN	Nanjing Pharmaceutical Factory	01 Jan 1982
Stomach Cancer	CN	Nanjing Pharmaceutical Factory	01 Jan 1982
Brain Cancer	US	Corden Pharma Latina SpA	04 Aug 1976
Hodgkin's Lymphoma	US	Corden Pharma Latina SpA	04 Aug 1976

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CTRI/2020/07/026696 (VAMANA, ASCO2024) Manual	Phase 2	Glioblastoma	46	bevacizumab+CCNU	jhqbmciewc(xkgbwvwdce) = efkmrdkggq rhmlwppowo (kaywzsfioz, 5.474 - 6.793) View more	Positive	02 Jun 2024
NCT01775475 (CTgov)	Phase 2	AIDS-Related Lymphoma \| AIDS-Related Diffuse Large Cell Lymphoma \| Immunoblastic Large-Cell Lymphoma	7	laboratory biomarker analysis+cyclophosphamide+prednisone+doxorubicin hydrochloride+vincristine sulfate (Arm I (CHOP))	mlgzrsrpil(dwdijcnvlz) = tngewalsis wnwilimmyi (bysvfpilfv, zknnudimbq - txehbpaqwk) View more	-	10 Oct 2022
				laboratory biomarker analysis+etoposide+cyclophosphamide+lomustine+procarbazine hydrochloride (Arm II (Oral Chemotherapy))	mlgzrsrpil(dwdijcnvlz) = gzfzojsupc wnwilimmyi (bysvfpilfv, cejystyzpn - iulsfvqilo) View more
NCT03022578 (CTgov)	Phase 2	Recurrent Glioblastoma	7	Laser Interstitial Thermal Therapy+Lomustine	kyrqttxsga(koduoqdruy) = bgfvkbcnsx snnndyanar (butropjtwz, vssrkchacy - jxqpfcbwnq) View more	-	10 Aug 2022
NCT02076152 (CTgov)	Not Applicable	Recurrent Glioblastoma	11	FMISO PET+Bevacizumab (FMISO PET & MRI Group 1)	bdatcrkosw(mkpzwimhvg) = qxlxscbegm rzakqdagxi (mfxadzbdem, rwepmxkjoz - owmadyzmpt) View more	-	30 Jul 2021
				FMISO PET+CCNU+Bevacizumab (FMISO PET & MRI Group 2)	bdatcrkosw(mkpzwimhvg) = yslvvlccrv rzakqdagxi (mfxadzbdem, fzudlvcnwu - hqanyigwrc) View more
NCT02343406 (INTELLANCE 2/EORTC 1410, Pubmed \| Neuro Oncol)	Phase 2	EGFR mutation Glioblastoma	260	Depatux-M alone	uoygvxeclx(eecaqfagen) = occurring as grade 3-4 in 25-30% of patients xqhrfxvuqz (kblublfuiq )	Positive	15 May 2020
				Depatux-M with temozolomide
NCT00590837 (LAMSA-2007, EHA2020)	Phase 3	Acute Myeloid Leukemia	330	Lomustine + idarubicin and cytarabine (ICL)	rnzqixauqr(wxlrodjggf): HR = 0.61 (95% CI, 0.4 - 0.93), P-Value = 0.023	Positive	14 May 2020
				Idarubicin and cytarabine (IC)
NCT00058370 (CTgov)	Not Applicable	Medulloblastoma	6	adjuvant therapy+lomustine+Cisplatin+vincristine sulfate	feiyreqcmb(udvguaxgoz) = inhtlhbjcp dkwebxrael (xnxnzvqrei, ncphlcpauo - bxugtlwxkf) View more	-	11 May 2020
NCT01067469 (CTgov)	Phase 2	Glioblastoma Multiforme	83	Standard Dose Bevacizumab (Standard Dose Bevacizumab)	eflropkpus(cohaoaszew) = piiufwzzsh gbfigdqnbb (obotwwjfbm, djykzzkucs - nlcgzlptzy) View more	-	17 Mar 2020
				Low Dose Bevacizumab+Lomustine (Low Dose Bevacizumab + Lomustine)	eflropkpus(cohaoaszew) = wijkbefwdv gbfigdqnbb (obotwwjfbm, hsqsnhtgct - fgygsavpgd) View more
NCT00031590 (CTgov)	Phase 2	Infratentorial Neoplasms \| Medulloblastoma	30	Craniospinal Radiation+Etoposide+Cyclophosphamide+Lomustine+Cisplatin+Vincristine	tnmanwmaba(arxqzwfnel) = yaklnqhjjo vsgxukutto (bmqutcflth, flgfylvxfx - kteseczlsv) View more	-	25 Apr 2019

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