3-D protein structure reveals a new mechanism for future anti-cancer drugs

Medical Xpress | February 15, 2019

A research team at the Medical University of South Carolina (MUSC) has discovered a new mechanism for a class of anti-cancer drugs known as E1 inhibitors. Their findings, published in Nature Communications on December 4, 2018, reveal a novel binding site that will promote drug design of more efficient E1 inhibitors. The team was led by Shaun Olsen, Ph.D., an assistant professor of Biology and Molecular Biology at MUSC and a member of the Developmental Cancer Therapeutics Program at Hollings Cancer Center. Olsen has dedicated his career to solving 3-D structures of proteins. Olsen and his team use these protein structures to model interactions with other molecules, including potential new drugs.
In the article, Olsen and his team report that they have discovered a new site on a protein, SUMO E1, which is a target for E1 inhibitors. The new binding site is located in the center of the protein and was previously thought to be out of reach. Olsen's team discovered an alternative conformation of the protein that exposes the site and allows a new inhibitor (COH000; Sumo Biosciences, Inc., Pasadena, CA) to bind.

Spotlight

The infographic explains how the process is in fact quick and completely pain-free, as well as highlighting the benefits of collecting immediately after birth as the umbilical cord contains a rich source of potentially lifesaving cells that have been left over from the placenta.

Spotlight

The infographic explains how the process is in fact quick and completely pain-free, as well as highlighting the benefits of collecting immediately after birth as the umbilical cord contains a rich source of potentially lifesaving cells that have been left over from the placenta.

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INDUSTRIAL IMPACT

Alloy Therapeutics and Normunity Sign Multi-Program Antibody Discovery Collaboration in Immuno-Oncology

Alloy Therapeutics | November 18, 2022

Alloy Therapeutics, a biotechnology ecosystem company, announced an antibody discovery collaboration spanning multiple precision immuno-oncology programs for Normunity, a biotech company that recently announced its $65 million Series A financing. The collaboration will support the advancement of Normunity’s immune normalizers, antibody therapies designed to target novel mechanisms that free the body’s normal immunity to fight cancer, which are conceived through a unique biotech-academic collaboration with a renowned immuno-oncology university research lab. Alloy democratizes access to tools, technologies, and services that are foundational for discovering and developing therapeutic biologics and has partnered with more than 130 discovery teams across academia, biotech, and large biopharma organizations. Through its discovery services offering, Alloy conducts high-touch, bespoke therapeutic discovery campaigns against partners’ targets of interest. “Our partnership reflects an exciting opportunity to pair Normunity’s insights in immune disruption and cancer disease biology with Alloy’s world-class antibody discovery expertise. We value Alloy’s collaborative approach and look forward to working together to advance the best therapeutic antibodies to target mechanisms discovered through Normunity’s platforms.” Normunity Chief Scientific Officer William LaRochelle, PhD The collaboration between Alloy and Normunity is leveraging Alloy’s high velocity antibody discovery services offering, Daedamab, which takes a sequencing-first approach to antibody discovery that reduces discovery timelines without sacrificing quality. The Daedamab team is based in Alloy’s research facility in Athens, GA, and its workflow comprises the ATX-Gx™, Alloy’s proprietary mice platform for human therapeutic antibody discovery, in addition to robust B cell isolation, next generation sequencing, cloning-free expression and a high throughput screening process—all supported by a rich informatics engine. “We are very excited to work with Normunity on its set of unique immuno-oncology targets using our high velocity NGS-based antibody discovery methods leveraging the ATX-Gx platform," said Richard Shimkets, PhD, SVP of Genetics and New Technologies at Alloy Therapeutics and CEO of the Daedamab site. “This relationship is emblematic of Alloy’s expertise in deploying the right technologies and processes to find our partners the best therapeutic antibodies against the novel targets they bring us.” Normunity is advancing into the clinic with programs that target mechanisms that drive the exclusion of T cells into immune-sensitive tumors and aim to deliver an active and effective immune system into cold tumors. About Daedamab Alloy’s Daedamab discovery service offers a novel, fast, powerful sequence-first approach to finding and making the best antibodies. The team is based in Athens, GA and supports Alloy collaborators with complete antibody discovery services, antibody sequencing of customer-provided material, expression and testing of customer-provided antibody sequences, humanization, and optimization services. About Alloy Therapeutics Alloy Therapeutics is a biotechnology ecosystem company empowering the global scientific community to make better medicines together. Through a community of partners across academia, biotech, and the largest biopharma, Alloy democratizes access to pre-competitive tools, technologies, services, and company creation capabilities that are foundational for discovering and developing therapeutic biologics across six modalities, including antibodies, TCRs, genetic medicines, peptides, cell therapies, and drug delivery. Partners may access all current and future technologies for a flat annual fee through Alloy’s Innovation Subscriptions offering. As a reflection of Alloy’s relentless commitment to the scientific community, Alloy reinvests 100% of its revenue in innovation and access to innovation. About Normunity Normunity, Inc., is a biotechnology company creating a new class of precision immuno-oncology medicines, called immune normalizers, that target novel mechanisms that free the body’s normal immunity against cancer. Based on an ongoing, interactive academic-biotech partnership with the lab of Dr. Lieping Chen at Yale School of Medicine, Normunity is targeting newly-discovered mechanisms of immune disruption in cancer based on proprietary discovery platforms that elucidate the complex interactions between human cancer and the immune system. The company is advancing an emerging pipeline of immune normalizers, including initial drug programs that target mechanisms that drive the exclusion of T-cells from immune-sensitive tumors and other mechanisms that are barriers to normal immune function in cancer. Normunity is located in Boston, Mass. and West Haven, Conn.

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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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INDUSTRIAL IMPACT

Ginkgo Bioworks Completes Acquisition of Zymergen

Ginkgo Bioworks | October 20, 2022

Today, Ginkgo Bioworks the leading horizontal platform for cell programming, and Zymergen announced that Ginkgo has completed its previously announced acquisition of Zymergen. The acquisition is expected to significantly enhance Ginkgo's platform by integrating strong automation and software capabilities as well as a wealth of experience across diverse biological engineering approaches. "Today marks an important step in our long-term growth as we complete the Zymergen acquisition and welcome their world-class team to Ginkgo. We are excited to integrate Zymergen's capabilities into our platform and explore new and expanded partnerships and opportunities for their diverse array of product concepts currently under development." Jason Kelly, CEO and co-founder of Ginkgo Bioworks Under the terms of the merger agreement entered into on July 24, 2022, Zymergen stockholders received, for each share of Zymergen common stock, 0.9179 shares of Ginkgo Class A common stock. Zymergen shares will no longer be traded on Nasdaq. Ginkgo Class A common stock will continue to trade on NYSE under the ticker symbol DNA. About Ginkgo Bioworks Ginkgo is building a platform to enable customers to program cells as easily as we can program computers. The company's platform is enabling biotechnology applications across diverse markets, from food and agriculture to industrial chemicals to pharmaceuticals. Ginkgo has also actively supported a number of COVID-19 response efforts, including K-12 pooled testing, vaccine manufacturing optimization and therapeutics discovery. About Zymergen Zymergen is a biotech company that designs and produces molecules, microbes and materials for diverse end markets. Zymergen partners with nature to make better products, a better way, for a better world.

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