Are Phages the Wave of the Future? Using Viruses to Treat Bacterial Diseases

biospace | May 16, 2018

Researchers with the University of Pittsburgh in Pennsylvania used a genetically modified bacteriophage—a type of virus that infects bacteria—to successfully treat 15-year-old Isabelle Carnell-Holdaway, a British girl with cystic fibrosis who had been fighting a drug-resistant Mycobacterium abscessus infection half her life. Her physician, Helen Spencer, with London’s Great Ormond Street Hospital, was out of options and reached out to Graham Hatfull at U of P. Their approach appeared to work, although they caution that because it was outside a controlled clinical trial, there may be other factors to their patient-specific cocktail. She continues to receive the treatments, which haven’t cured the infection, but appears to have it under control. The research was published in the journal Nature Medicine. Earlier this year, Ella Balasa, a 26-year-old from Richmond, Virginia, made the news when she was apparently successfully treated for a lung infection using a bacteriophage. Balasa has cystic fibrosis, which she was diagnosed with at the age of one year.

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Family farmer Bill Horan talks about how time - the most precious gift - has been given back to farmers and their families thanks to plant biotechnology.

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Family farmer Bill Horan talks about how time - the most precious gift - has been given back to farmers and their families thanks to plant biotechnology.

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CELL AND GENE THERAPY

Eiger BioPharmaceuticals Provides Update on Plans for Emergency Use Authorization Application Following FDA Feedback

Eiger BioPharmaceuticals, Inc. | October 06, 2022

Eiger BioPharmaceuticals, Inc. a commercial-stage biopharmaceutical company focused on the development of innovative therapies for hepatitis delta virus and other serious diseases, today announced that, following feedback from the U.S. Food and Drug Administration the company will not submit an emergency use authorization application of peginterferon lambda for the treatment of patients with mild-to-moderate COVID-19. Following Eiger's press release on September 6, 2022, the company submitted a pre-EUA meeting request to FDA, as well as additional morbidity and mortality outcomes data and analyses from the investigator-sponsored TOGETHER study. This included further statistical modeling and efficacy analyses of the study's primary and secondary endpoints and long-term follow-up data that the company believes continue to support the initial positive topline outcomes reported in March. In response, FDA denied the request for a pre-EUA meeting. Citing its concerns about the conduct of the TOGETHER study, FDA concluded that any authorization request based on these data is unlikely to meet the statutory criteria for issuance of an EUA in the current context of the pandemic. FDA suggested that, given peginterferon lambda's mechanism of action and the ongoing need for improved COVID-19 therapeutics, Eiger consider requesting an end-of-Phase 2 meeting to discuss a company-sponsored pivotal trial that could support an eventual Biologics License Application. Eiger is evaluating next steps for this program, in the U.S., as well as ex-U.S. emergency use authorization pathways and strategic options for continued development of peginterferon lambda for COVID-19 and other respiratory viral infections. "While we are disappointed that FDA will not consider an EUA application based on results generated from the TOGETHER study, we continue to have strong conviction in the potential of peginterferon lambda to confer a meaningful benefit for patients with COVID-19 and other respiratory viral infections. COVID-19 related deaths remain alarmingly high around the globe, including in the U.S. where, according to recent data from the Centers for Disease Control and Prevention, approximately 400 people die every day from this disease." David Cory, President and CEO, Eiger Eiger is advancing a late-stage pipeline of multiple FDA Breakthrough Therapy designated programs in Phase 3, including lonafarnib and peginterferon lambda for hepatitis delta virus (HDV) infection, and avexitide for congenital hyperinsulinism. The company expects to report topline data from D-LIVR, Eiger's landmark Phase 3 study of lonafarnib-based regimens for HDV, by year end. About TOGETHER Study TOGETHER is an independent multi-center, investigator-sponsored, randomized, placebo-controlled adaptive platform Phase 3 study evaluating therapeutics in newly diagnosed, high-risk, non-hospitalized patients with mild-to-moderate COVID-19. TOGETHER is the largest placebo-controlled study in COVID-19 and has evaluated 11 different therapeutic agents for non-hospitalized COVID-19 patients. The study was ongoing at the time the peginterferon lambda arm was added. The evaluation of peginterferon lambda versus placebo was the second largest study to date of a COVID-19 therapeutic of > 1,900 patients. Eligibility criteria required that all patients had laboratory-confirmed mild or moderate COVID-19 and were randomized within seven days of symptom onset. The study enrolled patients regardless of vaccination status or variant strain of SARS-CoV-2. The primary endpoint was a reduction in risk of clinical outcome comparing hospitalizations or emergency room visits greater than six hours after a single subcutaneous injection of peginterferon lambda versus placebo through Day 28. A key secondary endpoint was reduction in risk of hospitalizations or death in patients when dosed within three days of symptom onset. The TOGETHER study recruited from 12 sites in Brazil and 5 sites in Canada. About Peginterferon Lambda Peginterferon lambda is an investigational late-stage, first-in-class, type III interferon that stimulates immune responses that are critical for the development of host protection during viral infections and has been well-tolerated in clinical studies. Eiger is developing peginterferon lambda for the treatment of HDV infection. Peginterferon lambda has been administered to over 4,000 subjects in 28 clinical trials of HBV, HCV, HDV and COVID-19. Peginterferon lambda is an investigational agent and not yet approved for any indication. Eiger has received Orphan Designation by the U.S. Food and Drug Administration and European Medicines Agency, and Fast Track and Breakthrough Therapy Designation by FDA for peginterferon lambda in HDV. About Eiger Eiger is a commercial-stage biopharmaceutical company focused on the development of innovative therapies for hepatitis delta virus (HDV) and other serious diseases. The Eiger HDV platform includes two first-in-class therapies in Phase 3 that target critical host processes involved in viral replication.

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CELL AND GENE THERAPY

SQZ Biotechnologies and Collaborators Publish Technology Review on SQZ® APCs and Effective CD8 T Cell Activation

SQZ Biotechnologies | July 13, 2022

SQZ Biotechnologies Company focused on unlocking the full potential of cell therapies for multiple therapeutic areas, announced the publication of a technical review examining the ability of SQZ® Antigen Presenting Cells to activate CD8 T cells through MHC-I antigen presentation, an approach that may enable a more powerful T cell response and infiltration into solid tumors. Published in ESMO’s Immuno-Oncology and Technology journal, the review further explores the advantages of the company’s Cell Squeeze® technology in cell engineering and manufacturing as well as potential opportunities to develop additional clinical candidates with enhanced capabilities. “In this review, for patients with solid tumors, we discuss the critical need to generate CD8 T cell penetration into the tumor microenvironment. Activation of CD8 T cells through MHC-I antigen presentation is a promising approach and is being tested in the SQZ-PBMC-HPV-101 clinical trial where we’ve seen increases in CD8 T cell tumor infiltration and clinical benefit in a refractory patient with HPV16-mediated cancer. We look forward to potentially building on these early results through combination with various immunomodulatory drugs, such as checkpoint inhibitors.” lead author Jong Chul Park, MD, Medical Oncologist, Massachusetts General Hospital Cancer Center, and SQZ® cell therapy trial site investigator SQZ has three ongoing Phase 1/2 clinical trials aiming to drive CD8 T cell responses against HPV16+ solid tumors. Given the broad relevance of CD8 T cell responses across tumors, the authors highlight potential for future expansion of development programs into additional areas such as mutant KRAS, mutant TP53, EBV, and other patient-specific antigens. About SQZ-PBMC-HPV SQZ-PBMC-HPV is the company’s Antigen Presenting Cell (APC) autologous cell therapy clinical candidate and is derived from peripheral blood mononuclear cells (PBMCs), primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with tumor specific E6 and E7 peptide antigens. It received FDA fast track designation in April 2022. In December 2021, the company presented clinical data at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) congress that included a checkpoint refractory head-and-neck cancer patient who demonstrated a radiographic, symptomatic, and immune response in the monotherapy cohort of the Phase 1/2 clinical trial. SQZ-PBMC-HPV-101 Trial Design SQZ-PBMC-HPV is being evaluated in a Phase 1/2 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination phases of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a dose-limiting toxicity (DLT) window of 28 days and is designed to identify a recommended phase 2 dose. The planned combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors. DLT will be measured over 42 days. About Human Papillomavirus Positive Cancers Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years, often leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer, HPV+ tumors account for 4.5% of all cancers worldwide resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers. About SQZ Biotechnologies SQZ Biotechnologies is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies to benefit patients with cancer, autoimmune and infectious diseases. The company’s proprietary Cell Squeeze® technology offers the unique ability to deliver multiple biological materials into many patient cell types to engineer what we believe can be a broad range of potential therapeutics. Our goal is to create well-tolerated cell therapies that can provide therapeutic benefit for patients and improve the patient experience over existing cell therapy approaches. With accelerated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could change the way people think about cell therapies. The company’s first therapeutic applications seek to generate target-specific immune responses, both in activation for the treatment of solid tumors and in immune tolerance for the treatment of unwanted immune reactions and autoimmune diseases.

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INDUSTRIAL IMPACT

SIGA Announces Oncology Collaboration with KaliVir Immunotherapeutics

SIGA Technologies Inc. | July 16, 2022

SIGA Technologies, Inc. a commercial-stage pharmaceutical company focused on the health security market, today announced a collaboration with KaliVir Immunotherapeutics to make TPOXX® available for use with KaliVir’s proprietary oncolytic vaccinia immunotherapy platform. This novel oncolytic platform includes multiple proprietary genetic modifications that can be combined to generate a unique oncolytic virus that has been optimized for systemic delivery and anti-tumor immune stimulation. Under this partnership, SIGA is providing its TPOXX oral capsules to support future clinical programs. “KaliVir is an innovator in the creation of oncolytic viral immunotherapies, and we are excited to enter into this collaboration with them. TPOXX is a powerful antiviral drug to vaccinia and allows the safe use of higher doses of vaccinia vectors; there is also the potential it could increase immunotherapeutic outcomes. This collaboration helps bring new levels of assurance to physicians, regulators, and especially patients receiving these promising investigational therapies.” Dr. Phil Gomez, CEO of SIGA “We are pleased to announce this collaboration with SIGA Technologies,” said Helena Chaye, Ph.D., J.D., CEO of KaliVir. “Pairing oncolytic immunotherapies with an effective antiviral agent is a critical part of the development of new treatments, and we look forward to enhancing our groundbreaking oncolytic immunotherapy programs with the support of SIGA’s TPOXX.” On July 13, 2018, the U.S. Food and Drug Administration (FDA) approved oral TPOXX for the treatment of smallpox to mitigate the impact of a potential outbreak or bioterror attack. In preclinical studies, TPOXX has been shown to be active against most orthopoxviruses, including vaccinia The unique mechanism of action of TPOXX coupled with published efficacy in animal studies, make it an important addition to development programs focused on vaccinia-based cancer therapies. In 2020, SIGA entered into numerous collaborations, including a partnership with Turnstone Biologics to supply TPOXX to support Turnstone’s clinical oncolytic vaccinia immunotherapy programs. In 2021, SIGA entered into a preclinical research collaboration with Bioarchitech to investigate TPOXX enabling higher doses of vaccinia vectors when used in combination with Bioarchitech’s oncolytic vaccinia-based immunotherapy platform. ABOUT SIGA TECHNOLOGIES, INC. and TPOXX® SIGA Technologies, Inc. is a commercial-stage pharmaceutical company focused on the health security market. Health security comprises countermeasures for biological, chemical, radiological and nuclear attacks (biodefense market), vaccines and therapies for emerging infectious diseases, and health preparedness. Our lead product is TPOXX®, also known as tecovirimat and ST-246®, an orally administered and IV formulation antiviral drug for the treatment of human smallpox disease caused by variola virus. TPOXX is a novel small-molecule drug and the US maintains a supply of TPOXX under Project BioShield. The oral formulation of TPOXX was approved by the FDA for the treatment of smallpox in 2018. The full label is available by clicking here. Oral tecovirimat received approval from the European Medicines Agency (EMA) in 2022. The EMA approval includes labeling for oral tecovirimat indicating its use for the treatment of smallpox, monkeypox, cowpox, and vaccinia complications following vaccination against smallpox. The full label is available by clicking here. In September 2018, SIGA signed a contract with the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services, for additional procurement and development related to both oral and intravenous formulations of TPOXX. ABOUT KALIVIR IMMUNOTHERAPEUTICS. KaliVir Immunotherapeutics is a privately held biotech company developing cutting-edge, next-generation oncolytic viral immunotherapy programs. The company has developed a unique vaccinia virus-based platform that can generate potent novel oncolytic vaccinia viruses with modifications to maximize viral replication and to enhance intravenous delivery and spread (Vaccinia Enhanced Template “VET” Platform). VET™ platform utilizes the large transgene capacity of the vaccinia virus to deliver therapeutics matched to tumor immunophenotypes to stimulate patients’ immune systems and modify the tumor microenvironment. KaliVir’s oncolytic product candidates are designed to be safe, potent and systemically deliverable to treat cancer patients across multiple tumor types. KaliVir is in the process of advancing multiple therapeutic candidates toward the clinic.

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