On December 1, 2021 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported that David E. Anderson, Ph.D., VBI’s Chief Scientific Officer, will present updated 12-month and 18-month overall survival (OS) data from the Phase 2a study investigating VBI-1901, the Company’s cancer vaccine immunotherapeutic candidate targeting recurrent glioblastoma (GBM), at the World Vaccine & Immunotherapy Congress at 3:10 PM PT / 6:10 PM ET on December 1, 2021 (Press release, VBI Vaccines, DEC 1, 2021, View Source [SID1234596359]).

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Building on the data announced in June 2021, which supported the U.S. Food and Drug Administration (FDA) granting VBI-1901 Fast Track Designation for the treatment of recurrent GBM patients with first tumor recurrence, the updated data highlighted in Dr. Anderson’s presentation include:

Study arm 1 : VBI-1901 + granulocyte-macrophage colony-stimulating factor (GM-CSF)
18-month OS : 30% (n=3/10)
One patient remains on protocol past week 86, with a 93% tumor reduction relative to initiation of treatment at the beginning of the study
Two additional patients achieved OS of at least 20 months, but are no longer on protocol
Study arm 2 : VBI-1901 + GSK’s AS01 adjuvant system2
12-month OS : 70% (n=7/10)
18-month OS not yet reached
With few options for recurrent GBM patients, historical control data have demonstrated OS to be ~60% at 6-months and ~30% at 12-months after treatment with a monotherapy1.

"Data from the Phase 1/2a study have shown encouraging efficacy signals, including durable tumor responses and improvements in overall survival compared to historical controls, with a promising tolerability profile," said Patrick Y. Wen, M.D., Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute, Professor of Neurology at Harvard Medical School, and principal investigator of the INSIGhT trial. "These results merit further investigation especially as GBM patients have very limited treatment options, signaling a critical need for innovative new therapies to be assessed in the clinic. We will continue to evaluate VBI-1901 in the INSIGhT trial, with the hope of providing primary GBM patients alternative treatment options."

"We are very excited to be sharing these results as part of the World Vaccine & Immunotherapy Congress, and are inspired, in particular, by and for the patient who has achieved a 93% tumor reduction," said Dr. Anderson. "If we are able to replicate the tumor responses and overall survival data seen to-date in the next phases of development, we believe VBI-1901 could become a meaningful addition to a treatment field with very few options. We look forward to evaluating VBI-1901 in both primary and recurrent GBM settings and strive to provide hope for patients battling either stage of this aggressive and devastating brain cancer."

Next Steps for VBI-1901

Based on the data seen to date in the Phase 1/2a study in recurrent GBM patients, VBI expects to assess VBI-1901 in randomized, controlled clinical studies in both primary and recurrent GBM patients in the next phase of development.

Recurrent GBM :
Expected Q1 2022 initiation of enrollment of expanded number of patients in ongoing study in recurrent GBM, subject to discussions with the FDA, increasing study size and adding a control arm to support the potential for application for accelerated approval based upon tumor response data and improvements in overall survival
Primary GBM :
Beginning mid-year 2022, VBI expects to evaluate VBI-1901 in new investigational treatment arms of INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT), a Phase 2 adaptive platform trial
Patients will be randomized against a standard of care control arm, temozolomide in combination with radiotherapy, with a primary objective of improved overall survival in the frontline setting
To learn more about VBI’s ongoing Phase 1/2a study and the INSIGhT trial, visit clinicaltrials.gov (Respective Identifiers: NCT03382977 and NCT02977780).

World Vaccine & Immunotherapy Congress Presentation Details

Title: Development of eVLP platform for viral associated cancers
Presenter: David E. Anderson, Ph.D., VBI’s Chief Scientific Officer
Date: Wednesday, December 1, 2021
Time: 3:10 PM PT / 6:10 PM ET
About Fast Track Designation

The Fast Track program facilitates the expedited development and review of new drugs or biologics that are intended to: 1) treat serious or life-threatening conditions, and 2) demonstrate the potential to address unmet medical needs. A therapeutic that receives Fast Track Designation is eligible for some or all of the following: 1) more frequent meetings with FDA to discuss the development plan and data needed to support approval, 2) more frequent written communication from FDA relating to the design of the proposed clinical trials and use of biomarkers, 3) Accelerated Approval and Priority Review, if relevant criteria are met, and 4) Rolling Review, which means the company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, instead of waiting until all sections of the application are completed.

Fast Track Designation was granted to VBI-1901, adjuvanted with granulocyte macrophage colony-stimulating factor (GM-CSF), for the treatment of first-recurrent GBM.

About VBI-1901 and GBM

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. 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.

On December 1, 2021 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported it will host a virtual Investor Day on Wednesday, December 8, 2021 from 10:00 a.m. to 12:30 p.m. ET (Press release, Karyopharm, DEC 1, 2021, View Source,-2021 [SID1234596382]). Karyopharm’s executive management team will be joined by six recognized thought leaders in multiple myeloma, gynecological malignancies, myelodysplastic syndromes and myelofibrosis, including:

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Rafael Fonseca, MD, Mayo Clinic
Cristina Gasparetto, MD, Duke University Medical Center
Vicky Makker, MD, Memorial Sloan Kettering Cancer Center
Robert Coleman, MD, US Oncology Research
Guillermo Garcia-Manero, MD, MD Anderson Cancer Center
Srinivas Tantravahi, MBBS, MRCP, University of Utah
The virtual event will outline the Company’s commercial opportunities, refined corporate vision, pipeline priorities and corporate milestones that will support Karyopharm’s continued evolution toward a sustainable, fully-integrated development and commercialization organization.

To access the event, please dial (833) 989-2978 (local) or (236) 714-4042 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live video webcast of the event will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

On December 1, 2021 Adare Pharma Solutions ("Adare"), a technology-driven contract development and manufacturing organization (CDMO), reported the acquisition of Frontida BioPharm ("Frontida"), a vertically integrated CDMO focused on oral formulations (Press release, Frontida Biopharm, DEC 1, 2021, View Source [SID1234596324]). The acquisition reinforces Adare’s commitment to transform drug delivery by providing world class solutions from product development through commercial scale manufacturing and packaging. Adare’s portfolio of offerings for its customers will expand to include new capabilities such as high potency compound handling and packaging services. The combination of the two organizations will further establish Adare as a leader in the development and manufacturing of life saving medications in complex dosage forms.

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Vivek Sharma, Chief Executive Officer of Adare, commented, "We are devoted to improving the quality of life for patients by solving the most complex formulation challenges for our customers, and we believe this acquisition will bolster our ability to achieve our mission. Frontida and Adare share a commitment to quality and innovation, and we are excited to continue growing together. The combined company will lead in the space of oral formulations, while expanding the services and technical offerings we provide to meet the needs of our customers and their patients."

Dr. Song Li, Frontida’s Chairman added, "We are very excited about the opportunities this transaction is expected to provide to both existing and new clients. Our combined resources and capabilities will result in enhanced support and talent to ensure the success of their development and commercialization programs. This transaction is also a testament to the hard work, dedication, and caring culture of the team who has helped Frontida grow, enabling continued investment into the Philadelphia area, which is a respected home for pharmaceutical development and manufacturing. We look forward to continuing our work together to provide innovative, life-enhancing products to the US and global markets."

Together, the combined company will offer an expanded suite of solutions for complex oral formulations, such as taste masking, controlled release, high potency formulation manufacturing, and bioavailability enhancement. The addition of Frontida brings Adare’s manufacturing footprint to seven sites globally and expands Adare’s integrated, end-to-end offering to its partners. The combined organization will be led by Vivek Sharma.

Adare is backed by private equity firms Thomas H. Lee Partners and Frazier Healthcare Partners. RBC Capital Markets, LLC acted as exclusive financial advisor to Adare for this transaction.

On December 1, 2021 Notable Labs, Inc. (Notable), a clinical-stage predictive precision therapeutics company and CicloMed LLC (CicloMed), a developmental-stage pharmaceutical company reported that they have initiated a Phase 1B/2A clinical trial of fosciclopirox in patients with refractory acute myelogenous leukemia (AML) under the terms of a co-development agreement (Press release, Notable Labs, DEC 1, 2021, View Source [SID1234596343]). In the ongoing open-label, Phase 1B/2A trial currently underway at The University of Kansas Cancer Center, Notable is applying its high-fidelity predictive precision medicines platform with the goal of assessing patient responsiveness to fosciclopirox.

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"Notable’s unique predictive precision medicines platform has the potential to develop cancer treatments precisely for the patients predicted to respond, reducing the risks for patients of receiving treatments that don’t work for them. Moreover, developing a treatment in selected clinical responders enables smaller clinical trials and the potential to expedite development timelines," said Thomas Bock, M.D., Chief Executive Officer of Notable. "Fosciclopirox is a strategically and deliberately selected program, as it has already performed well on our predictive precision medicines platform."

"The initial phase of our collaboration with Notable focused on optimizing the Notable predictive precision medicine platform for sensitivity to fosciclopirox on AML patient samples," said Tammy Ham, CEO of CicloMed. "The encouraging results from this work led to our co-development agreement and the initiation of our on-going clinical trial."

Under the terms of the co-development agreement, CicloMed holds the primary responsibility for executing clinical trial operations while Notable is primarily focused on optimizing Notable’s predictive precision medicine platform. Both parties will be responsible for the costs associated with the on-going clinical trial.

About Fosciclopirox
Fosciclopirox was discovered by scientists at The University of Kansas Cancer Center, a National Cancer Institute designated cancer center and the Institute for Advancing Medical Innovation (IAMI), University of Kansas Medical Center’s product development enterprise. Fosciclopirox is part of an open-label, Phase 1B/2A study to characterize the efficacy, safety, PK, and pharmacodynamics of fosciclopirox administered alone and in combination with cytarabine in patients with relapsed or refractory AML. CicloMed was formed in 2016 as a public-private partnership between BioNovus Innovations LLC and IAMI, with fosciclopirox as the partnership’s lead drug development candidate.

On December 1, 2021 Humanigen, Inc. (Nasdaq:HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, reported The Lancet Respiratory Medicine ("Lancet"), an internationally trusted, peer-reviewed source of clinical, public health, and global health knowledge, published positive results from Humanigen’s LIVE-AIR Phase 3 randomized, controlled trial of lenzilumab in hospitalized COVID-19 patients, as well as an independent expert commentary (Press release, Humanigen, DEC 1, 2021, View Source [SID1234596361]). The Lancet paper concludes "LIVE-AIR showed that lenzilumab treatment of hospitalised patients with COVID-19 can improve the likelihood of survival without the need for mechanical ventilation, with a safety profile similar to that of placebo."2

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"Publication of LIVE-AIR results in this peer-reviewed medical journal is a major achievement. Our goal was to demonstrate that lenzilumab, a variant-agnostic therapy, could address the unmet need in treatment of COVID-19 patients by reducing death or mechanical ventilation. The results describe the positive impact lenzilumab has on improving survival without the need for invasive mechanical ventilation in COVID-19 patients upon hospitalization," said Cameron Durrant, Chairman and CEO, Humanigen. "As the paper describes ‘60% of LIVE-AIR patients were on room air or low-flow oxygen support. … (Raising) the possibility that lenzilumab might be positioned for use before ICU admission and progression of respiratory failure requiring high-flow oxygen and non-invasive or invasive ventilation.’"2

"This study of the treatment to prevent hyperinflammatory immune response that occurs in some patients infected with SARS-CoV-2 is important," said Zelalem Temesgen, M.D., Mayo Clinic infectious disease researcher and principal investigator. "The need is great for more therapies for newly hospitalized patients prior to respiratory failure to reduce mortality or mechanical ventilation."

Lenzilumab is not authorized, or approved, in any country.

"One of the key components of the detrimental hyperinflammatory response in COVID-19 is granulocyte-macrophage colony-stimulating factor (GM-CSF). … excessive GM-CSF production can contribute to the dysregulated immune response in severe COVID-19, in which, upstream of IL-1 and IL-6, activated T cells target neutrophils and macrophages. Agents that interfere with its actions have high plausibility for benefit, not just in COVID-19, but in other acute inflammatory conditions,"1 noted the commentary.

The Lancet paper notes differences in CRP levels for LIVE-AIR patients compared to those of clinical trials for another immunomodulator to suggest these "findings might indicate the therapeutic potential of targeting a single upstream cytokine earlier in the disease process, guided by baseline CRP. … The study contributes to the emerging body of evidence about how CRP concentrations relate to the pathogenesis of COVID-19 and to patient and treatment selection."2 Related to the value of a CRP-guided approach to treatment of COVID-19 patients, the commentary noted "further study of a CRP-guided approach, possibly targeting patients with lower CRP concentrations, earlier in their disease course, … could therefore be warranted."1

For hospitalized patients, "we now know that targeting the dysregulated host response is of greater value than targeting the virus."1 The high level of uncertainty and concern surrounding the emergence of the Omicron variant highlights the ongoing need for variant-agnostic therapies.

About the LIVE-AIR, Phase 3 Study of Lenzilumab

This study was a randomized, double-blind, placebo-controlled, multi-center Phase 3 trial for the treatment and prevention of serious and potentially fatal outcomes in patients hospitalized with COVID-19 pneumonia. The primary objective was to assess whether lenzilumab, in addition to other treatments, which included dexamethasone (or other steroids) and/or remdesivir, could prevent or alleviate the immune-mediated ‘cytokine storm’ and improve survival without ventilation, or ‘SWOV’ (sometimes referred to as ‘ventilator-free survival’). SWOV is a composite endpoint of time to death and time to invasive mechanical ventilation (IMV) and SWOV is an important clinical endpoint that measures not only mortality, but the morbidity associated with mechanical ventilation. Approximately 94% of patients received dexamethasone (or other steroids), 72% received remdesivir, and 69% received both.

The LIVE-AIR study enrolled 520 patients in 29 sites in the US and Brazil who were at least 18 years of age; experienced blood oxygen saturation (SpO2) of less than or equal to 94%; or required low-flow supplemental oxygen, or high-flow oxygen support, or non-invasive positive pressure ventilation; and were hospitalized but did not require IMV. Following enrollment, subjects were randomized to receive three infusions of either lenzilumab or placebo, with each infusion separated by eight hours over a 24-hour period. The LIVE-AIR study achieved its primary endpoint of survival without ventilation measured through day 28 following treatment (HR: 1.54; 95%CI: 1.02-2.32, p=0.040).

About Lenzilumab

Lenzilumab is a proprietary Humaneered first-in-class monoclonal antibody that has been proven to neutralize GM-CSF, a cytokine of critical importance in the hyperinflammatory cascade, sometimes referred to as cytokine release syndrome, or cytokine storm, associated with COVID-19 and other indications. Lenzilumab binds to and neutralizes GM-CSF, consequently improving outcomes for patients hospitalized with COVID-19. Humanigen believes that its GM-CSF neutralization has the potential to reduce the hyper-inflammatory cascade known as cytokine release syndrome common to chimeric antigen receptor T-cell (CAR-T) therapy and acute Graft versus Host Disease (aGvHD).

In CAR-T, lenzilumab successfully achieved the pre-specified primary endpoint at the recommended dose in a Phase 1b study with Yescarta in which the overall response rate was 100% and no patient experienced severe cytokine release syndrome or severe neurotoxicity. Based on these results, Humanigen plans to test lenzilumab in a randomized, multicenter, potentially registrational, Phase 2 study to evaluate its efficacy and safety when combined with other commercially available CD19 CAR-T therapies in non-Hodgkin lymphoma. Lenzilumab will also be tested to assess its ability to prevent and/or treat aGvHD in patients undergoing allogeneic hematopoietic stem cell transplantation.

A study of lenzilumab is also underway for patients with chronic myelomonocytic leukemia (CMML) exhibiting RAS pathway mutations. This study will build on evidence from a Phase 1 study, conducted by Humanigen, that showed RAS mutations are associated with hyper-proliferative features, which may be sensitive to GM-CSF neutralization.