On June 16, 2021 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 Manuel Litchman, M.D., President and Chief Executive Officer, will present at the Raymond James Human Health Innovation Conference, taking place virtually from June 21 – 23, 2021(Press release, Mustang Bio, JUN 16, 2021, View Source [SID1234584089]). The company will present on Wednesday, June 23, 2021, at 8:00 a.m. ET and will also participate in one-on-one meetings during the conference. A webcast of the company’s presentation will be available on the Events page of the Investor Relations section of Mustang’s website, www.mustangbio.com, for approximately 30 days after the meeting.

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On June 16, 2021 Kytopen, a transformative biotechnology company offering non-viral delivery that links the discovery, development and manufacturing of engineered cell therapies, reported it was awarded a SBIR Fast Track grant from the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institute of Health (NIH) (Press release, US NIH, JUN 16, 2021, View Source [SID1234584087]). Kytopen is eligible for up to $2M over the course of the 3-year award as project milestones are successfully completed within the Phase I and Phase II portions of the grant.
Natural killer (NK) cells represent a high impact population for cell therapy, but due to limitations in current methodologies for gene delivery, NK cells remain a largely untapped resource. This SBIR grant will be used to demonstrate that non-viral delivery via Kytopen’s Flowfect platform can alleviate this limitation on NK cell gene editing at both research and manufacturing scale, which is needed for pre-clinical and clinical studies. Due to the major potential impact NK cells represent in a clinical setting, non-viral Cas Ribonucleoprotein (RNP) gene knockout will allow for novel therapeutic applications in infectious disease, autoimmune disorders, and immuno-oncology.
Paulo Garcia, Kytopen’s CEO and Co-Founder will serve as the Principal Investigator (PI) on the grant. Dr. Garcia explains that "engineered NK cells have tremendous therapeutic promise including the potential to treat solid tumors in an allogeneic modality. The Flowfect platform will facilitate high-throughput target discovery while providing a clear path towards clinical manufacturing of next-generation cell products."
NK cells are a subset of innate immune cells that can respond to threat without antibody priming. This quick response to stimuli makes them an ideal immunotherapy candidate. Yet, genetic modification in NK cells has proven to be difficult using conventional viral and non-viral transfection methodologies. Alternative delivery methods are necessary in order to make genetic modifications at reproducible and efficient rates, while maintaining high cell viability and functionality.
The awarded study leverages continuous fluid flow coupled with low energy electric fields for transfection via a proprietary Flowfect platform (Figure 1). This platform represents a novel approach to non-viral delivery in historically "hard-to-transfect" human cells. The current research proposes to engineer non-activated NK cells with Cas RNPs for gene editing using the Flowfect platform. To achieve this goal, Kytopen has outlined a two-phase research strategy which focuses on stability and functionality of edited NK cells both in vitro and in vivo.
NIH sponsored grant programs are an integral source of capital for early-stage U.S. small businesses that are creating innovative technologies to improve human health. These programs help small businesses break into the federal research and development arena, create life-saving technologies, and stimulate economic growth. Kytopen is honored to be a recipient of this competitive award from the NIH/NIAID and looks forward to unlocking biological capabilities of engineered NK cells for improving patients’ lives during the performance of this project.

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About the Flowfect Technology
Kytopen’s proprietary Flowfect platform eliminates the complexity of gene editing and integrates discovery, development and manufacturing in one flexible and scalable non-viral delivery solution. The Flowfect technology utilizes electro-mechanical energy to disrupt the cell membrane and introduce genetic material (such as RNA, DNA, or CRISPR/Cas RNP) to a wide variety of hard-to-transfect primary cells. During the Flowfect process, a solution containing cells and genetic payload suspended in a proprietary buffer flows continuously through a channel while the solution is exposed to a low energy electric field. Due to the continuous flow and low electrical energy required, cells engineered using Flowfect exhibit high viability while also exhibiting high transfection efficiency post-processing. The Flowfect technology utilizes relatively high flow rates enabling cell engineering in minutes for discovery and optimization (e.g. 96 well plate in <10 minutes) and direct scale up to manufacturing volumes of >10mL, engineering over 2 billion cells per minute in a single channel.

On June 16, 2021 Servier, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that Clinical Cancer Research has published data from its Phase I study evaluating single-agent vorasidenib in isocitrate dehydrogenase (IDH) mutant advanced solid tumors, including low-grade glioma (Press release, Servier, JUN 16, 2021, View Source [SID1234584082]). Vorasidenib is an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes.

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In the first-in-human study (NCT02481154), vorasidenib demonstrated both a favorable safety profile at doses <100 mg once daily and preliminary clinical activity in recurrent or progressive IDH1/2 mutant low-grade glioma. The study data demonstrated a median progression-free survival of 36.8 months (3.1 years) [95% confidence interval (CI), 11.2–40.8 months] for patients with nonenhancing low-grade glioma. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG (RANO-LGG) in patients with nonenhancing low-grade glioma was 18% (one partial response, three minor responses). Exploratory evaluation of tumor volumes showed sustained tumor shrinkage in multiple patients with nonenhancing low-grade glioma.

"Given the toxicities associated with chemotherapy and radiation, there remains a significant unmet need to improve treatment options for patients living with IDH mutant low-grade glioma," said Tim Cloughesy, M.D., David Geffen School of Medicine, Department of Neurology, University of California, Los Angeles, an investigator for the Phase 1 study. "These early results reinforce the potential benefit of vorasidenib and the further exploration of more targeted therapies."

Mutations in the metabolic enzymes IDH1/2 occur in up to approximately 80% of patients with low-grade gliomas. Standard treatment of low-grade gliomas includes tumor resection, followed by radiation and chemotherapy as appropriate. This treatment is not curative and current therapy is associated with short- and long-term toxicity, with most patients experiencing disease recurrence and progression to a higher tumor grade. In this study, vorasidenib demonstrated a favorable safety profile. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible.

"We are excited to announce the publication of our first clinical data manuscript in glioma in Clinical Cancer Research, underscoring the potential benefit of vorasidenib in IDH mutant low-grade glioma," said Susan Pandya, M.D., Vice President, Clinical Development, Head of Cancer Metabolism Global Development, Servier Pharmaceuticals. "These data provide further support for our registration-enabling Phase 3 INDIGO study evaluating the activity of vorasidenib at an early stage of the disease where delaying the need for more aggressive treatments could provide a meaningful benefit to patients."

Vorasidenib is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma (NCT04164901).

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Vorasidenib Phase 1 Dose-Escalation Study

Vorasidenib, an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes, is being evaluated as a single agent in an ongoing Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid tumors (n=93), including glioma (n=52). Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment was completed in June 2017 (NCT02481154).

Vorasidenib INDIGO Phase 3 Study

Vorasidenib, an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes, is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma (NCT04164901).

About Glioma

Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low-grade glioma) to rapidly progressing (high-grade glioma-Glioblastoma Multiforme). Tumor enhancement is an imaging characteristic assessed by magnetic resonance imaging (MRI), and enhancing tumors are more likely to be high-grade.

Common symptoms of glioma include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor, and regardless of treatment, the majority of patients with low-grade gliomas will have recurrent disease that will progress over time. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80% have an IDH mutation.

On June 16, 2021 ImmunoGenesis, a clinical-stage biotechnology company developing therapeutics to catalyze effective immune responses in immunologically cold cancers, reported the publication in Clinical Cancer Research of results from a Phase 1 trial of evofosfamide, the only known reducer of solid tumor hypoxia, combined with an immune checkpoint inhibitor, ipilimumab, in patients with advanced cancer (Press release, ImmunoGenesis, JUN 16, 2021, View Source [SID1234584081]). The journal article, "A Phase 1 Dose Escalation Study to Evaluate the Safety and Tolerability of Evofosfamide in Combination with Ipilimumab in Advanced Solid Malignancies," highlights an overall response rate of 17% and a disease control rate of 83% across four dose levels in 21 heavily pre-treated patients. In addition, a clear biomarker picture emerged with pre-existing immune gene signatures correlating with response to therapy and hypermetabolic signatures predicting progression. Responders also showed improved cellular signatures of anti-tumor immunity.

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"A hostile tumor metabolism is a major source of immune resistance in certain tumors," said James Barlow, ImmunoGenesis President and CEO. "Evofosfamide, with the demonstrated ability to reduce tumor hypoxia, can be a critical component of facilitating immunotherapy efficacy in these tumors. With these compelling results in hand, we look forward to advancing our development pipeline."

"Along with others in the field, I had identified tumor hypoxia as a barrier to effective tumor immunity in certain tumors," said Michael Curran, PhD, founder of ImmunoGenesis. "These exciting Phase 1 data support preclinical observations in which evofosfamide reversed tumor hypoxia and facilitated the efficacy of checkpoint inhibition. The efficacy of the combination in these heavily pre-treated patients appears superior to checkpoint monotherapy and provides strong rationale for the use of evofosfamide as a tumor conditioning agent."

The study was led at The University of Texas MD Anderson Cancer Center by Curran, Associate Professor of Immunology and David S. Hong, M.D., Professor of Investigational Cancer Therapeutics. Dr. Curran has a personal financial relationship with ImmunoGenesis, which is managed and monitored by the MD Anderson Conflict of Interest Committee.

About the Phase 1 Study
The Phase 1 (NCT03098160), dose-escalation study tested evofosfamide in combination with ipilimumab administered in four three-week cycles in heavily pre-treated patients with castration-resistant prostate cancer, advanced pancreatic cancer, immunotherapy-resistant melanoma, and advanced HPV-negative head and neck cancer. The combination regimen was well-tolerated, with most drug–related-adverse events being grade 1–2. There were no unexpected safety signals.

About Evofosfamide
Evofosfamide is a 2-nitroimidazole prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM) originally developed as a hypoxia-activated prodrug. Through his research, Dr. Curran discovered that evofosfamide can reduce hypoxia in solid tumors. In pre-clinical models, evofosfamide restored T cell function and synergized with checkpoint inhibition. ImmunoGenesis is developing evofosfamide as a hypoxia-reversal agent that can condition tumors to respond to checkpoint inhibition.

On June 16, 2021 Harbour BioMed (HKEX: 02142) reported that it has entered into a multi-year, multifaceted research collaboration agreement with Dana-Farber Cancer Institute to co-develop novel biotherapies in cancer treatment(Press release, Harbour BioMed, JUN 16, 2021, View Source [SID1234584080]).

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Harbour BioMed scientists and Dana-Farber researchers will be working together to develop novel oncologic drugs, including bispecific antibodies and CAR-T cell products. In recent years, bispecific antibodies and CAR-T cell therapies are both considered as the next-generation solutions in the tumor immunology field. For their ability to engage two different targets, bispecific antibodies are expected to extend the possibilities of monoclonal antibody (mAb) therapeutics, and CAR-T cell therapy is an innovative immunotherapy that uses specially altered T-cells to redirect them to target cancer cells.

This strategic collaboration will leverage Harbour BioMed’s transgenic Harbour Mice platform with Dana-Farber’s expertise in CAR-T cell development and basic oncology research to generate novel biotherapies.

Harbour BioMed’s antibody technology platforms – Harbour Mice, which is based on two proprietary transgenic mouse platforms will be utilized to generate human therapeutic antibodies. The platforms have broad potential for generating both conventional as well as next-generation biologics, such as bi- and multi-specifics, CAR-Ts or VH domain-derived products that are fully human, affinity matured with excellent solubility and developability.

"We are delighted to initiate this collaboration with Harbour BioMed. The complementary technology and expertise between Harbour and DFCI will dramatically shorten the interval from novel discovery to developing optimized antibody and cellular therapies for clinical translation," said Dr. Eric Smith, Laboratory Principal Investigator & Director of Translational Research for Immune Effector Cell Therapies at Dana-Farber Cancer Institute.

"The collaboration with world renowned Dana-Farber Cancer Institute demonstrates HBM’s commitment to developing novel medicines and fostering fast-track innovative research. I believe this collaboration will be ultimately translated into better treatments for cancer patients," said Jingsong Wang, Founder, Chairman & Chief Executive Officer of HBM.