On November 4, 2020 BioInvent International AB ("BioInvent" or the "Company") (OMXS: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported it will present new clinical and preclinical data on its novel anti-FcγRIIB antibody, BI-1206, at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place virtually on December 5-8, 2020 (Press release, BioInvent, NOV 4, 2020, View Source [SID1234569869]).

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This includes preliminary data from a Phase I/IIa trial of BI-1206 in combination with rituximab in patients with follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) who have relapsed or are refractory to rituximab.

The data demonstrate that increasing doses of BI-1206 from 30 mg to 70 or 100 mg gave rise to a supra-proportional increase in the maximum concentration recorded, as well as an increase in the half-life of BI-1206. In addition, the higher dose levels (70 or 100 mg) showed close to full receptor saturation up to 72 hours. Increasing the dose further will likely give rise to sustained receptor saturation over an extended period. Furthermore, complete (CR) and partial (PR) clinical responses, as assessed by reduction of tumor size, were observed, in particular in the 70 mg cohort, where 3 of 5 patients have shown clinical responses.

"These data are very encouraging and indicate the strong potential of BI-1206 to make a significant difference to patients with relapsed or refractory indolent NHL. In particular, these preliminary data suggest that BI-1206 is generating the first signs of clinical responses in patients who have relapsed after treatment with rituximab. Importantly, overcoming target-mediated drug disposition will allow weekly or even less frequent dosing," said Martin Welschof, CEO of BioInvent.

"Our recent China licensing agreement for BI-1206 with CASI Pharmaceuticals is an important validation of BioInvent’s technology, expertise and business model. It provides further impetus to our lead drug candidate, and we look forward to continuing development of this novel treatment option in hematological cancers and solid tumors, and bringing it closer to the market."

BioInvent will also present results from two preclinical studies with BI-1206. Results from the first study show that BI-1206 had single agent activity in a patient-derived xenograft (PDX) model comprising ibrutinib-venetoclax resistant MCL cells in vivo. BI-1206 enhanced the in vivo efficacy of ibrutinib plus rituximab and venetoclax plus rituximab and overcame resistance to these treatments, resulting in enhanced anti-tumor effects.

In the second preclinical study in mice, pre-medication with two doses of corticosteroids (16-24h and 1h prior to infusion) prevented infusion-related reactions associated with intravenous anti-FcyRIIB administration. This pre-medication regimen has been implemented in the clinical trials of BI-1206 and shown to greatly improve the tolerability profile.

BI-1206 has a novel mode-of-action, blocking the single inhibitory antibody checkpoint receptor FcγRIIB to unlock anti-cancer immunity in both liquid and solid tumors. BI-1206 is BioInvent’s lead drug candidate and is being investigated in a Phase I/II trial, in combination with anti-PD1 therapy Keytruda (pembrolizumab), in solid tumors, and in a Phase I/IIa trial in combination with MabThera (rituximab) for the treatment of non-Hodgkin lymphoma (NHL).

Details of the abstracts:

17-BI-1206-02 Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to FcyRIIB, in Combination with Rituximab in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab > Link

Targeting Antibody Checkpoint FcyRIIB Using Monoclonal Antibody BI-1206 to Overcome Therapeutic Resistance in Mantle Cell Lymphoma > Link

Establishment of an in vivo mouse model to study and overcome infusion related reactions associated with FcyRIIB antibody administration > Link

On November 4, 2020 CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported data in seven patients from two ongoing Phase 1/2 clinical trials of the investigational CRISPR/Cas9 gene-editing therapy CTX001 in severe hemoglobinopathies has been accepted for an oral presentation during the Plenary Scientific Session at the annual ASH (Free ASH Whitepaper) Meeting and Exposition, which will take place virtually from December 5-8, 2020 (Press release, CRISPR Therapeutics, NOV 4, 2020, View Source [SID1234569868]). Haydar Frangoul, M.D., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute, HCA Healthcare’s TriStar Centennial Medical Center, will deliver the presentation on behalf of all the authors on December 6, 2020.

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An abstract posted online today includes data from five patients with three months to 15 months of follow-up after CTX001 infusion in the ongoing Phase 1/2 CLIMB-111 trial in transfusion-dependent beta thalassemia (TDT) and data from two patients with three months and 12 months of follow-up in the ongoing Phase 1/2 CLIMB-121 trial in severe sickle cell disease (SCD). Additional data will be presented at ASH (Free ASH Whitepaper), including longer-duration follow-up data for the patients included in the abstract and data for additional patients with greater than three months of follow-up.

CTX001 is being investigated in these two ongoing clinical trials as a potential one-time curative therapy for patients suffering from TDT and severe SCD.

The accepted abstract is now available on the ASH (Free ASH Whitepaper) conference website.

About CTX001
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and reduce painful and debilitating sickle crises for SCD patients.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA). CTX001 has also been granted Orphan Drug Designation from the European Commission for both TDT and SCD, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for SCD.

CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex. Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About CLIMB-111
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About the Gene-Editing Process in These Trials
Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease and for safety.

About the CRISPR-Vertex Collaboration
CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. CRISPR Therapeutics and Vertex will jointly develop and commercialize CTX001 and equally share all research and development costs and profits worldwide.

On November 4, 2020 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that interim Phase 1/2 data on MB-106, a CD20-targeted, autologous CAR T cell therapy for patients with relapsed or refractory B-cell non-Hodgkin lymphoma ("NHL"), have been selected for a poster presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting, which is being held virtually from December 5 – 8, 2020 (Press release, Mustang Bio, NOV 4, 2020, View Source [SID1234569867]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Research Center ("Fred Hutch").

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In the abstract posted today on the ASH (Free ASH Whitepaper) website, Fred Hutch reported on four patients treated following a major revision in the cell manufacturing process. Complete remissions were observed in two follicular lymphoma patients (one each at dose levels 1 and 2), as well as a partial remission in a mantle cell lymphoma patient at dose level 2 and progressive disease in a follicular lymphoma patient at dose level 1. Dose level 1 was 3.3 x 105 CAR-T cells/kg and dose level 2 was 1 x 106 CAR-T cells/kg. As previously disclosed, no responses were seen in the 7 patients treated prior to cell process revision. Among the 11 total patients reported in the abstract, there was one occurrence of cytokine release syndrome (grade 3 – unexplained alkaline phosphatase elevation in the setting of fever in a patient treated prior to cell process revision) and no occurrences of immune effector cell-associated neurotoxicity syndrome (any grade). No dose-limiting toxicity was observed.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are pleased that Fred Hutch will present interim data at ASH (Free ASH Whitepaper) from the ongoing Phase 1/2 trial of MB-106, and at that time we expect to disclose data on at least eight total patients treated since the major cell process revision. In February 2020, we reported that the first patient treated in the trial with the revised MB-106 manufacturing process achieved a complete response at the lowest starting dose. The additional data disclosed today further indicate that MB-106 has an extremely favorable safety profile with evidence of promising clinical activity, even at low dose levels. We look forward to continuing progress on this CD20-targeted CAR T cell therapy program for patients with relapsed or refractory B-cell non-Hodgkin lymphomas."

Details of the presentation are as follows:

Title: Third Generation CD20 Targeted CAR T-Cell Therapy (MB-106) for Treatment of Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
Session: 704. Immunotherapies: Poster I
Abstract: 1443
Date and Time: Saturday, December 5, 2020, 10:00 a.m. – 6:30 p.m. ET
Presenter: Mazyar Shadman, M.D., M.P.H., Associate Professor, Clinical Research Division, Fred Hutch, Seattle, WA

For more information, please visit the 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition website at View Source

About B-cell Non-Hodgkin Lymphoma (NHL)
There are several forms of NHL, including follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma and small lymphocytic lymphoma, which account collectively for about 45% of all cases of NHL. Most types of NHL are incurable with available therapies, except for allogenic hematopoietic stem cell transplant (allo-SCT). More than 70,000 new cases of B-cell NHL are diagnosed each year in the United States, and more than 19,000 patients die annually due to this group of diseases.

About MB-106 (CD20-targeted CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research partner, Fred Hutchinson Cancer Research Center ("Fred Hutch"), in the laboratory of Oliver Press, M.D., Ph.D., and Brian Till, M.D., in the Clinical Research Division and exclusively licensed to Mustang Bio in 2017. MB-106 has been optimized as a third-generation CAR derived from a fully human antibody and is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in B-cell non-Hodgkin lymphoma patients. Additional information on the trial can be found at View Source using the identifier NCT03277729.

On November 4, 2020 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has received the clinical hold letter from the U.S. Food and Drug Administration (FDA) with respect to its Investigational New Drug Application (IND) (Press release, PharmaCyte Biotech, NOV 4, 2020, View Source [SID1234569866]). The company had previously announced on October 2, 2020 that it has received notification from the FDA that its IND had been placed on clinical hold.

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In order to lift the clinical hold, the FDA has informed the company that it needs to conduct several additional preclinical studies. The FDA also requested additional information regarding several topics, including data, manufacturing information and product release specifications.

In addition, the FDA requested that several items not related to the clinical hold be addressed via submission of an IND amendment. Specifically, the FDA requested that the company perform qualification studies for the drug substance filling step to ensure that the product remains sterile and stable during the filling process. The FDA also requested additional information, discussion and clarification on several other topics.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said, "Our team of experts is developing action plans to address the clinical hold letter. Since the FDA’s letter included a lengthy list of items and several preclinical studies, at this time it’s impossible to say when the company will be in a position to submit a complete response to the FDA. One big reason for the uncertainty is because some of the preclinical studies will be performed by outside third-party laboratories. Also, we are planning to request a meeting with the FDA about some of its requests. So, this is currently a very fluid situation."

Once PharmaCyte files its response to the clinical hold letter, the FDA will have 30 days to review the material submitted by PharmaCyte and make its decision whether to lift the hold.

On November 4, 2020 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (TSXV: IPA) (OTCQB: IPATF) (FSE: TQB2), a leader in full-service, therapeutic antibody discovery and development, reported that it intends to complete a consolidation of its issued and outstanding common shares ("Common Shares") on the basis of one (1) new Common Share for every five (5) Common Shares presently issued and outstanding (the "Consolidation"). Completion of the Consolidation remains subject to the approval of the TSX Venture Exchange (the "TSXV") (Press release, ImmunoPrecise Antibodies, NOV 4, 2020, View Source [SID1234569865]).

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Pursuant to the articles of the Company, the Board of Directors ("Board") of the Company has approved the Consolidation by way of Board resolutions. The Consolidation is being conducted to meet one of the listing rules of the Nasdaq Capital Market ("Nasdaq"), which require the Company to maintain a minimum bid price per Common Share, in connection with a potential listing of the Company’s Common Shares on Nasdaq. The Board believes the Consolidation and a Nasdaq listing will enable the Company to gain increased liquidity and trading volume and broaden the Company’s investor base.

Upon receipt of TSXV approval of the Consolidation, IPA will provide additional details regarding a new CUSIP number for its Common Shares to distinguish between the pre- and post-consolidated Common Shares. IPA’s name and trading symbol will remain unchanged. Following the completion of the Consolidation, the Company will have approximately 16,700,000 Common Shares issued and outstanding.

Upon completion of the Consolidation, letters of transmittal describing the details of the Consolidation and the process by which shareholders obtain actual share certificates representing the consolidated Common Shares will be mailed to IPA’s registered shareholders. Registered shareholders will also be able to obtain copies of the letter of transmittal by contacting their brokers or other intermediary, or IPA’s transfer agent, Computershare Trust Company of Canada.

Shareholders who hold their shares through their broker or other intermediary and do not have actual share certificates registered in their name will not be required to complete and return a letter of transmittal. Any pre-consolidation Common Shares owned by such shareholders will automatically be adjusted as a result of the Consolidation to reflect the applicable number of post-consolidation Common Shares owned by them and no further action is required to be taken by such shareholders. If, as a result of the Consolidation, a shareholder becomes entitled to a fractional share, such fractions will be rounded to the nearest whole Common Share.