On April 20, 2022 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm,’ reported a peer-reviewed publication in Leukemia, a leading oncology and hematology journal, entitled "GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity (Press release, Humanigen, APR 20, 2022, View Source [SID1234612593])."

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This publication is a significant addition to the findings from a previous article in the leading hematology journal, blood, which demonstrated that neutralization of GM-CSF with lenzilumab (LENZ) was able to break the efficacy/toxicity linkage by reducing cytokine release syndrome (CRS) and neuroinflammation (ICANS) while enhancing CAR-T function.1 The Leukemia publication demonstrates that CRISPR/Cas9-mediated GM-CSF knockout in CAR-T cells directly ameliorates CAR-T cell early activation, reduces activation-induced cell death, and results in enhanced anti-tumor activity in vivo in a xenograft model.2

Enhancing CAR-T cell in vivo efficacy by using strategies to non-specifically stimulate CAR-T cell proliferation utilizing synthetic biology or combination therapy to edit exhaustion pathways or prevent apoptosis is an important goal and is the subject of substantial ongoing research. However, while this may improve CAR-T efficacy, it is often at the cost of an increase in important toxicities, such as CRS and ICANS. In contrast, these data published in Leukemia indicate that GM-CSFko CAR-T cells result in enhanced CAR-T cell proliferation and anti-tumor activity while being associated with a marked reduction in GM-CSF levels, which have been linked to CAR-T associated toxicities.

CAR-T therapies have resulted in significant advances for patients. However, for up to one-third of patients, toxicities such as severe ICANS and CRS occur, and tumor relapse is still a frequent occurrence.3 Currently, the widespread adoption of CAR-T therapy is limited, in part, by the requirement for treatment in centers that are experienced in managing the common toxicities of ICANS and CRS and by the financial and health burden that this creates. "CRS, ICANS, and tumor relapse remain challenges for physicians and patients treated with CAR-T therapy," said Saad Kenderian, M.B., Ch.B., hematologist at Mayo Clinic Cancer Center, an author of the Leukemia paper and the primary investigator for the SHIELD study (Study on How to Improve Efficacy and toxicity with Lenzilumab in DLBCL and other NHL patients treated with CAR-T therapy). He added, "They result in additional morbidity for patients, as well as significantly increased costs for healthcare providers. Treatments that can prevent ICANS and CRS while potentially improving CAR-T efficacy could address a critical unmet need."

This publication adds to the body of knowledge of GM-CSF depletion in CAR-T. The upcoming Phase 3 CAR-T study, known as SHIELD, will determine the efficacy and safety of prophylactic lenzilumab on the rates of ICANS, CRS, and CAR-T efficacy. "The SHIELD trial has been designed to build on the positive results from the ZUMA-19 study. The primary endpoint of SHIELD will focus on demonstrating a significant improvement in neurotoxicity associated with both Yescarta and Tecartus. We will also seek to explore the beneficial impact that lenzilumab may have CAR-T efficacy," stated Dale Chappell, M.D., MBA, Chief Scientific Officer, Humanigen.

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, potentially improving outcomes for patients hospitalized with COVID-19. Humanigen believes that GM-CSF neutralization with lenzilumab also 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 (ZUMA-19) 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 3 study ("SHIELD") to evaluate its efficacy and safety when combined with Yescarta and Tecartus CAR-T therapies in non-Hodgkin lymphoma. Lenzilumab will also be tested to assess its ability to prevent and/or treat acute Graft versus Host Disease (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 builds 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.

Lenzilumab is an investigational product and is not approved or authorized in any country.

On April 20, 2022 CytRx Corporation (OTCQB: CYTR) ("CytRx" or the "Company"), a biopharmaceutical innovator focused on research and development of life-saving cancer therapeutics, reported it has partnered with oncology development expert Gilad Gordon, MD to assist the Company in developing its next-generation LADR drugs toward first-in-human clinical trials (Press release, CytRx, APR 20, 2022, View Source [SID1234612592]).

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Dr. Gordon is President of ORRA Group, LLC, a consultancy focused on assisting companies in drug development efforts, particularly in oncology. Dr. Gordon brings 30 years of experience in the development of oncology therapeutics, having led clinical teams in multi-national Phase I through Phase III trials. Throughout his career, Dr. Gordon has participated in the filing of over 50 Investigational New Drug ("IND") applications, has had responsibility for hundreds of clinical trials in cancer and has been responsible for the final market approvals of approximately five cancer therapeutics that went on to help cancer patients. In addition, Dr. Gordon was a senior member of the management team that sold Inviragen, Inc. to Takeda Pharmaceutical Company Limited for $250 million and has been involved in raising more than $2 billion through IPOs, venture funding and other partnership programs.

CytRx CEO Dr. Stephen Snowdy commented:

"We are really excited to have someone with Dr. Gordon’s experience in developing cancer therapies working with us to move our next-generation LADR drugs closer to saving lives. CytRx is committed to moving these cancer assets toward IND filing as quickly and capital-efficiently as possible and is working hard to find the most expedient path possible. The difficult market environment has not impacted our confidence in LADR or our resolve to unlock shareholder value through advancement of our LADR-based drugs."

Dr. Gordon added:

"Globally, there are 17 million new cancer cases per year, and 10 million deaths due to cancer. Additional treatments for this disease are desperately needed. CytRx’s unique LADR backbone allows for the targeting of drugs to tumors, and subsequent concentration and release of drugs in the tumor, which is expected to reduce toxicity and increase efficacy. This elegant approach has the added benefit of being based on small molecules, which offers advantages in manufacturing and toxicity relative to large molecules, such as antibodies or liposomal particles. The first LADR drug, Aldoxorubicin, has provided validation of the LADR approach in multiple clinical trials, allowing several-fold higher dosing of doxorubicin than would be possible without the LADR backbone, and is in late-stage clinical trials for pancreatic cancer. Most importantly, the preclinical data on the next-generation LADR drugs is very impressive, and I look forward to helping guide these products through clinical testing and the regulatory process."

Dr. Gordon attended Harvard College and received his MD from Harvard Medical School. He is Board-certified in Internal Medicine and received his Master of Business Administration from the University of Washington. He is a Clinical Associate Professor of Medicine at the University of Colorado.

On April 20, 2022 Monopteros Therapeutics Inc. ("Monopteros"), a clinical-stage biotechnology company developing MPT-0118, a first-in-class MALT1 inhibitor for the treatment of solid tumors, reported two presentations at the tumor immune microenvironment workshop of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), to be held in person in San Diego and virtually from April 21-22, 2022 (Press release, Monopteros Therapeutics, APR 20, 2022, View Source [SID1234612591]). These presentations demonstrate that highly activated immunosuppressive regulatory T cells (Tregs) in solid tumors have the potential to become interferon-gamma-producing effector T cells and that the occurrence of this reprogrammed state increases the clinical response to immune checkpoint therapy in cancer patients. Further, translational nonclinical results for MPT-0118, currently undergoing a phase 1 clinical trial (NCT04859777), are presented.

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"We are excited to present these results, which shed light on how a cold, unresponsive, and immunosuppressive tumor microenvironment can be modulated to respond to immunotherapy," said Peter Keller, President and CEO of Monopteros. "Our clinical candidate MPT-0118 is pioneering the novel mechanism of reprogramming tumor-infiltrating regulatory T cells, which is the key for opening up many cold tumors to immunotherapy."

Presentation Title: Spontaneous proinflammatory conversion of regulatory T cells (Treg) is associated with improved immune checkpoint inhibitor (CPI) response
Poster Number: 042
Presenter: Kevin Litchfield, PhD, University College of London
Presentation Date and Time: April 21, 5:20 to 6:20 pm PT
Results show that around 4% of Tregs in cancer are spontaneously producing interferon-gamma. This Treg population is associated with a higher probability of response to anti-PD-1 checkpoint inhibitor therapy in cancer patients. We further demonstrate that these reprogrammed Tregs are genetically related to a pool of highly activated PD1 and Lag3 positive Tregs.

Presentation Title: Reprogramming Regulatory T cells (Treg) Using a MALT1 Inhibitor for Cancer Therapy
Poster Number: 037
Presenter: Peter Keller, MSc, Monopteros Therapeutics
Presentation Date and Time: April 21, 5:20 to 6:20 pm PT
This poster was requested for resubmission from SITC (Free SITC Whitepaper)’s annual conference in 2021 and presents the data generated with clinical-stage MPT-0118 to reprogram regulatory T cells in mouse and human tissue and its preclinical anti-tumor effects.

Following the conference, the two presentations will be available in the Publications section of Monopteros’ website at www.monopterostx.com.

On April 20, 2022 Seagen Inc. (Nasdaq: SGEN) reported plans to build a new facility in Everett, Washington, to expand the company’s biomanufacturing capacity and enable the company greater control and flexibility over the production of its medicines to treat cancer (Press release, Seagen, APR 20, 2022, View Source [SID1234612590]). The 270,000-square-foot facility will be built north of the company’s U.S. headquarters in Bothell, Washington. Seagen expects to have the facility operational in 2024 and ultimately employ up to 200 highly skilled workers to produce medicines for clinical trials and the commercial market.

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"In cancer research and development, Seagen must continue to be agile and flexible, especially in manufacturing, to advance our promising pipeline of medicines for people living with cancer and bring these medicines to patients as fast as possible," said Clay Siegall, Ph.D., President and Chief Executive Officer, Seagen. "This new biomanufacturing facility is another way we are growing and expanding operations while also positioning ourselves to attract top-flight talent to drive our business priorities."

The new biomanufacturing facility is a "greenfield" project, constructed from the ground up into a modern production facility to make advanced medicines. Seagen plans to make antibody-based medicines (also called biologics) in the new fully integrated plant for the commercial market and for use in clinical sites around the world. The new facility will add to Seagen’s existing manufacturing site in the Bothell area. This project will create up to 150 new jobs during the initial construction of the shell and core of the building.

Seagen has four marketed therapies used in the treatment of Hodgkin lymphoma and urothelial (bladder), breast and cervical cancers. In research and development, Seagen is advancing more than 17 programs, including approved products and a deep and diverse early- and late-stage pipeline across a range of solid tumors and hematologic malignancies.

As a global biotech company, Seagen employs more than 2,800 people worldwide including more than 1,600 people in the Pacific Northwest.

On April 20, 2022 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported that it will host a key opinion leader (KOL) webinar on Nana-val (nanatinostat and valganciclovir) for the treatment of advanced Epstein-Barr virus-positive (EBV+) solid tumors on Wednesday, April 27, 2022, at 11:00 AM EDT (Press release, Viracta Therapeutics, APR 20, 2022, View Source [SID1234612588]).

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The webinar will feature a presentation from KOL Ezra Cohen, MD, FRCPSC, FASCO (Chief of Hematology/Oncology, Department of Medicine and Co-director of the Gleiberman Head and Neck Cancer Center, University of California, San Diego), who will discuss the current treatment landscape in nasopharyngeal carcinoma (NPC) and the unmet medical need for the treatment of patients with NPC.

Additionally, members of Viracta’s management team will provide an overview of the ongoing Phase 1b/2 clinical trial evaluating Nana-val in patients with recurrent or metastatic NPC and other advanced EBV+ solid tumors. Preclinical data supporting the use of Nana-val in solid tumors and the program’s future outlook will also be discussed.

A live question and answer session will follow the formal presentation.

To register for the webinar, please click here. Following the event, materials from the presentation and a replay of the webcast will be available in the "Events and Webcasts" section of the Viracta website at View Source

KOL Biography
Ezra Cohen, MD, FRCPSC, FASCO, is the Chief of the Division of Hematology-Oncology, and Co- Director of the San Diego Center for Precision Immunotherapy. A physician-scientist, Dr. Cohen led an independently funded laboratory interested in investigating the mechanisms of action of novel therapeutics and made major contributions to the development of targeted- and immuno- therapies. His research in areas such as epidermal growth factor receptor inhibitors, cell therapy, and immunotherapy in head and neck cancer has received peer-reviewed funding. He has made major contributions to the understanding of critical signaling pathways, the integration of novel agents into standard of care, and to the defining of mechanisms to overcome resistance to drug therapy. He also recently co-developed a personalized neoantigen vaccine using unique cancer mutations to boost an anti-tumor immune response.

Dr. Cohen also serves as Associate Director for Clinical Science, Co-Leader of the Solid Tumor Therapeutics Research Program and Co-Director of the Hanna and Mark Gleiberman Head and Neck Cancer Center at Moores Cancer Center. Additionally, he is a member of the Protocol Review and Monitoring Committee (PRMC), the Cancer Council, and the Cancer Center’s Executive Committee.

About Nana-val (Nanatinostat and Valganciclovir)

Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which is key to inducing viral genes that are epigenetically silenced in EBV-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-Val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed/refractory EBV+ lymphoma (NAVAL-1) as well as a multinational Phase1b/2 trial in patients with EBV+ recurrent or metastatic nasopharyngeal carcinoma and other EBV+ solid tumors.

About EBV-Associated Cancers

Approximately 90% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV+ lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden and is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.