On December 1, 2021 TOT BIOPHARM International Company Limited (TOT BIOPHARM, 1875.HK) reported its self-developed Pusintin (TAB008, bevacizumab injection) has been officially granted approval by the National Medical Products Administration ("NMPA") for marketing in mainland China (i.e., excluding Hong Kong, Macau and Taiwan regions) for the treatment of patients with advanced, metastatic or recurrent non-squamous non-small cell lung cancer and patients with metastatic colorectal cancer (Press release, Tot Biopharm, DEC 1, 2021, View Source [SID1234596363]). Pusintin is the first antibody drug of TOT BIOPHARM approved for marketing.

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Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF) which can specifically bind to VEGF and block the binding of VEGF to its receptor, thereby reducing angiogenesis and inducing degeneration of existing blood vessels, and inhibit tumor growth. As a broad-spectrum anti-tumor drug, bevacizumab injection has become a globally recommended standard therapy in the treatment guidelines for a variety of malignant tumors, which had abundant real-world evidence of its efficacy and safety since its entry into the market in 2004. Bevacizumab injection has currently been included in the National Medical Insurance Directory. According to the Frost & Sullivan Report, bevacizumab’s market share in China will increase to RMB 6.4 billion in 2023 and RMB 9.9 billion in 2030.

Pusintin is a biosimilar to bevacizumab injection sold under the trade name of Avastin in China. TOT BIOPHARM strictly followed the NMPA’s "Guidelines on Similarity Evaluation and Indication Extrapolation of Biosimilars" and has taken rigorous and comprehensive head-to-head comparisons between Pusintin and the reference bevacizumab. The results from pharmaceutical studies, non-clinical studies, and clinical studies proved that Pusintin has similar PK characteristics with the originator drug and presents clinically equivalent with highly similarity in safety and immunogenicity.

Bevacizumab has been approved for 8 indications globally, and 6 indications in China, including mCRC, NSCLC, glioblastoma multiforme (GBM), and for the treatment of hepatocellular carcinoma (HCC), ovarian cancer, and cervical cancer. According to the "Guidelines on Similarity Evaluation and Indication Extrapolation of Biosimilars", Pusintin will be eligible for application by way of extrapolation for use in all indications of Avastin approved in China.

TOT BIOPHARM has established large-scale commercial production base in Suzhou Industrial Park that meets international standards, covering an area of 50,000 square meters with a capacity of monoclonal antibodies reaches 20,000L until the first half of 2022. Pusintin adopts the self-developed Perfusion-batch mixed culture technology (PB-Hybrid Technology) for commercial production. This technology has been verified in the production of Phase III clinical drugs, which can simplify the process and shorten the production cycle, reduce production costs, and greatly improve the cost advantage of Pusintin.

Dr. Liu Jun, CEO of TOT BIOPHARM, said, "We are very pleased for the Pusintin ‘s marketing approval of NMPA, which can provide high-quality and affordable treatment options for more cancer patients. This is really a key milestone for TOT BIOPHARM. Meanwhile, it has once again verified the superiority of our one-stop innovative drug R&D and production platform. By virtue of our highly competitive commercial production platform and technology platform, we will constantly accelerate the implementation of innovative achievements and improve the availability of medicines, and let the achievements of national medicine benefit more patients."

On December 1, 2021 MEI Pharma, Inc. (Nasdaq: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported that it has priced the underwritten public offering of 17,500,000 shares of its common stock at $2.60 per share for total gross proceeds (before underwriting discount and commissions and estimated expenses) of $45,500,000 (Press release, MEI Pharma, DEC 1, 2021, View Source [SID1234596362]). In connection with the offering, the Company granted the underwriters a 30-day option to purchase up to an additional 2,625,000 shares of common stock offered in the public offering. The offering is expected to close on December 6, 2021, subject to the satisfaction of customary closing conditions.

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The Company plans to use the net proceeds of the offering, together with other available funds, to progress its clinical development programs, prepare for and support the commercial launch of zandelisib, subject to receiving FDA marketing approval, and for other general corporate purposes.

Jefferies, Stifel and Wells Fargo Securities are acting as joint book-running managers for the offering. LifeSci Capital and H.C. Wainwright & Co. are acting as co-managers for the offering.

The securities described above are being offered pursuant to a "shelf" registration statement previously filed and declared effective by the Securities and Exchange Commission (SEC). The offering is being made only by means of a prospectus supplement and accompanying base prospectus.

When available, copies of the final prospectus supplement and accompanying base prospectus relating to the offering may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022 or by email at [email protected]; Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at 415-364-2720 or by email at [email protected]; or Wells Fargo Securities, LLC, Attention: Equity Syndicate Department, 500 West 33rd Street, New York, New York 10001 at 833-690-2713 or email a request to [email protected]. An electronic copy of the preliminary prospectus supplement and accompanying base prospectus relating to the offering will also be available on the website of the SEC at www.sec.gov.

This release does not constitute an offer to sell, or the solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.

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.

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 SimBioSys, the technology company that predicts tumor responses to therapy, reported that new research on the accuracy and specificity of their simulation software, TumorScope, for breast cancer treatment planning during the 2021 San Antonio Breast Cancer Symposium (SABCS) (Press release, SimBioSys, DEC 1, 2021, View Source [SID1234596358]). The studies covering eight separate posters at SABCS are based on data from both internal and external validation studies of SimBioSys’ proprietary platform. The results include biophysical simulations of neoadjuvant therapy (a preliminary step to begin shrinking a tumor); biological drivers for different racial groups including African Americans vs Caucasians; prognostic responses to identify the patients who will, or will not, benefit from various chemotherapies; and characterization of the tumor’s microenvironment.

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TumorScope is a first-of-its-kind platform combining artificial intelligence with biophysical simulations to model the impact of phenomena such as drug delivery, metabolism, and spatial heterogeneity in a comprehensive model using standard-of-care data alone. The results are generated within minutes, enabling physicians to make a well-informed decision while improving patient experience and shared decision-making. In addition, the technology can support the drug development process across pre-clinical and clinical trial settings.

"Breast cancer continues to be at the forefront of the precision medicine movement, and yet clinicians have been unable to individualize care for patients. Beyond our clinical utility in treatment selection, we are excited to expand TumorScope for use in biopharma for clinical trial optimization and biomarker identification," said John Cole, Ph.D., Chief Scientific Officer at SimBioSys. "Having eight posters accepted at the SABCS speaks to the breadth of our platform. We are proud of the work and the results that our multidisciplinary R&D team has accomplished in breast cancer."

Key SimBioSys studies from the symposium include:

Virtual replication of the NeoSphere trial using SimBioSys TumorScope: Associating standard of care data with clinical outcomes in HER2 positive breast cancer patients to garnish novel insights in silico
Brief Summary: Matched analysis using SimBioSys virtual tumor bank (3000+ patient tumors) and the Neosphere trial created an in silico virtual clinical trial of 144 HER2+ breast cancer patients. TumorScope biophysical simulations were able to predict equivalent rates of pCR and disease progression to the Neosphere trial. In the near future, virtual clinical trials may curtail the need for real-world clinical trials, enabling more efficient drug discovery. (Date/time: Wednesday, 12/8, 5:00 pm – 6:30 pm CT.)
SimBioSys TumorScope: Biophysical modeling of patient-specific response to chemotherapy
Brief Summary: TumorScope constructed 3D in silico tumor models from patient’s pretreatment DCE-MRIs through the combination of a spatial model with vascular data, tumor metabolism, pharmacokinetic and pharmacodynamic models. Validation was performed across 780 breast cancer patients (n=480 with EFS data available). Tumor volumetric response predictions were calculated with an error rate 0.03% and a mean absolute deviation of 8.2% in patients that underwent neoadjuvant chemotherapy. (Date/time: Wednesday, 12/8, 7:00 am – 8:30 am CT.)
Evaluation of the prognostic accuracy of SimBioSys TumorScope in early breast cancer
Brief Summary: Blinded study conducted prospectively using retrospective data with the University of Chicago (n=141) for patients who received neoadjuvant chemotherapy for early stage breast cancer. TumorScope accurately predicted event free survival in patients, comparable to the predictive accuracy of pCR. TumorScope demonstrates utility in guiding escalation and de-escalation of treatment regimens. (Date/time: Thursday, 12/9, 5:00 pm – 6:30 pm CT.)
A transdisciplinary approach for characterizing racial differences in the biology of breast cancer by integrating imaging and -omics data
Brief Summary: Using imaging and transcriptomic data from over 500 patients, TumorScope biophysical modeling software demonstrates how multi-modal imaging and systems biology models of patient tumors shed light on metabolic features that drive differences in response between African American and Caucasian tumors. The data assists with understanding chemotherapeutic drug responses (high spatial heterogeneity of drug delivery and secretion) and improving clinical management. (Thursday, 12/9, 7:00 am – 8:30 am CT.)