Lomustine

Kazia Therapeutics saw the survival signal after pruning the control cohort. Kazia Therapeutics has found a way to try to salvage a win from a failed late-phase brain cancer trial. By removing part of the control arm, the biotech has emerged with survival data it will share with the FDA to see whether a path to accelerated approval has opened up.  The data come from a platform study sponsored by the Global Coalition for Adaptive Research. The trial has enrolled patients with newly diagnosed and recurrent glioblastoma, a hard-to-treat brain cancer, to receive molecules developed by companies including Bayer and Biohaven. The design allows researchers to compare a revolving cast of candidates to a standard-of-care control arm in a single study. In August 2022, Kazia said its contribution to the study, a PI3K/mTOR inhibitor discovered by Genentech, failed to meet the threshold for advancing to the next stage of the trial. Now, Kazia has shared the data behind the failure—and made the case that there is a positive story to tell.  Investigators enrolled two subgroups of patients to receive Kazia’s candidate paxalisib. The molecule was numerically worse than the control treatment, lomustine, in patients with recurrent disease, achieving a median overall survival (OS) of 8.05 months compared to 9.69 months for the standard of care. That part of the study featured 213 patients, split roughly evenly between paxalisib and the control. Kazia focused its discussion of the data on the other subgroup, which enrolled newly diagnosed patients with a form of the disease that is less likely to respond to the chemotherapy drug temozolomide. In that subgroup, Kazia reported a median OS of 14.77 months in 54 recipients of paxalisib. The result was barely better than the 13.84 months seen in the temozolomide control cohort. However, Kazia found a subset of the control arm that painted a better picture of paxalisib. Because paxalisib was added to the platform trial around 18 months after the study began, roughly one-third of the 75 patients in the newly diagnosed control arm were enrolled before dosing of Kazia’s drug candidate started. Limiting the control arm to the 46 patients who were enrolled concurrently to Kazia’s prospect resulted in a median OS of 11.89 months. Kazia CEO John Friend, M.D., hailed the result as a “3.8 month improvement in overall survival, an approximate 33% improvement,” in a statement. The biotech now plans to discuss the data with the FDA to “determine if a potential path to accelerated approval is appropriate for paxalisib.” Kazia’s share price rose around 70% in premarket trading, but that jump only brought it up to 33 cents.

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.