Eight biotechs thriving in Seattle

Known for its significant musical influences since the early 20th century, the city of Seattle is largely dependent on healthcare services for its economy. Its place in the country’s biotech industry is growing steadily, and biotech employment has grown by 24% in the past five years. In this article, let us take a look at some of the major biotech companies in Seattle that are contributing to the biotech industry at large.

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    A-Alpha Bio

    Specializing in synthetic biology, A-Alpha Bio has developed experimental and computational platforms to engineer protein-protein interactions.

    The experimental platform AlphaSeq can generate protein interaction data at scale. This is done by characterizing protein-protein interaction networks with millions of interactions to aid in antibody and molecular glue target discovery and protein interface engineering. The AlphaBind computational platform uses machine learning to predict the binding strength from protein sequences. The two platforms work in tandem to synthesize and validate protein sequences, and therefore drive antibody discovery.

    In its immunocytokine therapeutics pipeline, A-Alpha Bio has three candidates focused on oncology and autoimmune disease, all of which are in the discovery stage. 

    In September, the Seattle based biotech company announced its extended partnership with multinational Amgen to discover  molecular glues. Last year, it also received $22.4 million to scale its platforms and boost pipeline development. 

    Adaptive Biotechnologies

    Seattle-based biotech company Adaptive Biotechnologies has developed the Immune Medicine Platform, which sequences T and B cell receptors that are mapped to antigens to identify which diseases a patient’s immune system is fighting. These receptors are then characterized to learn which ones would be most effective for cell-based or antibody-based therapies.

    With the help of this platform, the company aims to identify and treat autoimmune diseases, cancer, infectious diseases and neurodegenerative diseases. It has more than 58 billion receptors in its immunomics database, and the platform has received the U.S. Food and Drug Administration (FDA) nod for four indications, namely acute lymphoblastic leukemia, multiple myeloma, chronic lymphocytic leukemia, and COVID-19.

    Its T cell receptor therapies are being developed in collaboration with American multinational company Genentech, and is being designed to identify a cancer target through a tumor biopsy, as well as attack a patient’s specific neoantigen. As part of its antibody therapeutics, the biotech has characterized neutralizing antibodies that bind to different regions of the SARS-CoV-2 virus, in order to treat COVID-19 in patients.

    Moreover, Adaptive Biotechnologies’ clonoSEQ aims to monitor measurable residual disease (MRD) in patients. MRD refers to a small number of cancer cells that are still left in the body after treatment. ClonoSEQ has obtained FDA clearance for leukemia and multiple myeloma.

    Avalyn Pharma

    Focused on treating rare lung diseases, Avalyn Pharma has a number of preclinical and clinical candidates.

    Its phase 2 candidate AP01 contains pirfenidone, which is a small molecule inhibitor designed to treat idiopathic pulmonary fibrosis. Unlike an oral pirfenidone formulation, which is associated with side effects like diarrhea, photosensitivity, rashes and fatigue, Avalyn Pharma’s inhaled aerosol lung delivery of AP01 allows small doses directly to the lungs, maximizing the effect and sparing tissues outside the lungs.

    The Seattle-based biotech company has also developed AP02, which is made up of nintedanib – a small molecule inhibitor of multiple tyrosine kinases – and is delivered via inhalation. The candidate was found to be well-tolerated, indicative of efficient inhaled alveolar deposition, and it delivered oral-superior lung levels with reduced systemic exposure, according to phase 1a results.

    For further development of AP01 and AP02, Avalyn Pharma secured $175 million in a series C round in September.

    Kineta

    Kineta is immersed in the field of immuno-oncology. Its Innate Immunity Development Platform seeks to address the mechanisms of cancer immune resistance by developing human antibodies.

    Its lead candidate KVA12123 is a fully human engineered IgG1 monoclonal antibody, which has been designed to bind to the target VISTA. This target drives immunosuppression in the tumor microenvironment and suppresses T cell function in solid tumors. So, blocking VISTA can help inhibit tumor growth and improve the effectiveness of T cell therapies.

    KVA12123 is currently undergoing a phase 1 study in patients with advanced solid tumors, where it will be tested as a monotherapy, as well as in combination with Merck’s Keytruda. In preclinical studies, the candidate showed tumor growth inhibition in cold tumors – tumors that typically respond poorly to treatment. It also showed no signs of neurotoxicity in models, and will be further studied in the phase 1 safety trial. 

    Last month, it announced that KVA12123 had cleared the first four monotherapy dose levels and the first cohort when administered with Keytruda. No dose limiting toxicities have been observed so far.

    In its pipeline, Kineta also has an anti-CD27 agonist mAb immunotherapy, which is tasked with the challenging job of reversing T cell exhaustion. When activated, the target CD27 lowers the activation threshold of T cells against low affinity tumor antigens. Anti-CD27 monoclonal antibodies can help activate the maturation of naïve T cells and even natural killer cells, which can induce an anti-tumor response in cells.

    Lumen Bioscience

    Seattle-based biotech company Lumen Bioscience aims to develop affordable, high-dose antibodies for oral and topical delivery by using an suprising organism: spirulina 

    As spirulina cells express more proteins than most other food crops, these cells are introduced to a gene encoding an antibody or any therapeutic molecule. As the spirulina grows, its cells generate and store the therapeutic protein. The cells are then harvested by spray-drying the biomass, and the therapeutic protein is retrieved. The powder is packed into capsules and stored at room temperature. When ingested, the cells are protected by their cell membrane, and the proteins are released when they arrive at the small intestine where they neutralize the disease targets.

    Based on this technique, the company’s preclinical and clinical candidates are designed to treat infectious and metabolic diseases. Its C. difficile colitis candidate is in phase 1 studies after being granted Fast Track Designation by the FDA, and its traveler’s diarrhea candidate is in phase 2.

    Last year, Lumen Bioscience was awarded $5.5 million by the U.S. Department of Defense to support the development of needle-free vaccines, as well as $16.2 million to take its C. difficile-targeting candidate to late-stage clinical trials, and $8.1 million to treat viral respiratory conditions. It also bagged the Wilkes Center Climate Prize which was worth $1.5 million.

    Sound Pharmaceuticals

    Around 50 million people in the U.S. are affected by hearing loss or tinnitus. There are no FDA-approved treatments for disorders of the inner ear. Sound Pharmaceuticals aims to change this by developing therapies for sensorineural hearing loss.

    Most advanced in its pipeline is the candidate SPI-1005, which is being tested for Meniere’s disease, a rare inner ear condition that can affect your balance and hearing, and can cause sudden vertigo. SPI-1005, which contains the chemical ebselen, is currently in phase 3 trials. Ebselen helps reduce neuroinflammation in the nervous system and induce glutathione peroxidase (GPx) activity, which is reduced in hearing loss. 

    Sound Pharmaceuticals is also involved in the cystic fibrosis space. Earlier this month, the Seattle-based biotech company presented encouraging interim data from a phase 2b study evaluating SPI-1005 in treating ototoxicity in patients with cystic fibrosis. The data showed a 4% and 43% decrease in the ototoxicity rate with 400 and 600 mg doses respectively.

    SPI-1005 is also in phase 2 trials for the treatment of COVID-19, for which it has received a $4.2 million grant from the National Institutes of Health (NIH).

    TwinStrand Biosciences

    Next-Generation Sequencing (NGS) is a massive parallel DNA sequencing method that offers ultra-high throughput, scalability, and speed. However, this technology does come with certain challenges like low accuracy and short sequencing read length. Seattle-based TwinStrand Biosciences’ goal is to overcome these limitations with the help of its Duplex Sequencing technology.

    The sequencing mechanism is capable of revealing true mutations. It is said to be more accurate – supposedly by 10,000 fold – when compared to standard NGS, and can eliminate background errors..

    Its AML MRD assay is the only error-corrected NGS-based technology that provides ultrasensitive detection of MRD-associated mutations in acute myeloid leukemia (AML). 

    In a patent dispute over its DNA sequencing technology, cancer blood test developer Guardant Health has been forced to pay TwinStrand Biosciences more than $83 million in damages, in November. TwinStrand claimed that Guardant infringed on its patents through its Guardant360 blood and tissue kits. Guardant looks to appeal.

    Umoja Biopharma

    Immunotherapy company Umoja Biopharma, develops chimeric antigen receptor (CAR)-T cell therapies for hard-to-treat solid tumors.

    Umoja aims to overcome the challenges of cell therapies by engineering T cells to battle tumors while reducing adverse events in patients. Its VivoVec gene delivery platform uses lentiviral vectors to transport the CAR-T cells to specific tumor sites and attack them. This is combined with its Rapamycin-Activated Cytokine Receptor (RACR) technology, which employs rapamycin to support the survival of the CAR-T cells. Lastly, its TUMORTAG tags the tumors so that CAR-T cells can identify the targets more easily, making the attack more precise.

    Most advanced in its TUMORTAG program is UB-TT170, which targets a folate receptor, and is in phase 1 trials. In the preclinical stage, it is developing three candidates that target PSMA, CA IX, and FAP, in solid tumors.

    The Seattle biotech company has also partnered with American pharmaceutical AbbVie to develop UB-VV111, which is poised to enter the clinic later this year. UB-VV111 is being designed to target the antigen CD19 for a hematological indication.

    It presented preclinical data at the 65th American Society of Hematology Annual Meeting in December. According to the data, CAR-T cells were efficiently generated after one injection of VivoVec, and the cells helped kill target antigen-expressing cells.

    New Seattle hub to expedite biotech innovation with leading companies

    The Seattle Hub for Synthetic Biology is being set up to monitor and record genomic changes in millions of cells to better understand how healthy cells are affected by diseases and track disease progression. The initiative is a collaboration between Allen Institute, Chan Zuckerberg Initiative and the University of Washington in Seattle. One of the key technologies involved is the ‘DNA Typewriter’ created by the Allen Institute. This is a molecular recorder that consists of CRISPR–Cas9 target sites. The project was awarded $75 million, which will fund the hub for five years.

    Besides biotech companies, Seattle also has big pharmaceuticals setting up shop in the city. Bristol Myers Squibb has employed more than 1500 people in the region, and its research and development teams are expediting cell therapy manufacture. The pharma giant has invested $149 million in small businesses, boosting the city’s economy and employment opportunities.