List of RNAi Companies with Phase 2 Active Clinical Trial - 8

Arbutus Biopharma Corporation, a biopharmaceutical company, engages in the discovery, development, and commercialization of a cure for patients suffering from chronic Hepatitis B virus (HBV) infection in the United States. Its HBV product pipeline consists of AB-729, a proprietary subcutaneously-delivered RNA interference product candidate, which in an ongoing Phase Ia/Ib clinical trial targeted to hepatocytes that inhibits viral replication and reduces various HBV antigens using novel covalently conjugated GalNAc delivery technology; and AB-836, an oral capsid inhibitor that suppresses HBV DNA replication. The company’s research and development programs include HBV RNA destabilizers, an orally active agent to destabilize HBV RNA, which leads to RNA degradation and to reduction in HBV proteins; oral PD-L1 inhibitor to enable reawakening patients’ HBV-specific immune response; and small molecule antiviral medicines to treat coronaviruses, including COVID-19. It has strategic alliance, licensing, and research collaboration agreements with Marqibo; Gritstone Oncology, Inc.; and Alnylam Pharmaceuticals, Inc. and Acuitas Therapeutics, Inc. The company was formerly known as Tekmira Pharmaceuticals Corporation and changed its name to Arbutus Biopharma Corporation in July 2015. Arbutus Biopharma Corporation is headquartered in Warminster, Pennsylvania.

Benitec is a biotechnology company developing a proprietary therapeutic technology platform that combines RNA interference (RNAi) with gene therapy with a goal of providing sustained, long-lasting silencing of disease-causing genes from a single administration. Benitec is using its technology, called DNA-directed RNA interference (ddRNAi) to develop a pipeline of product candidates for the treatment of several chronic and life-threatening human diseases , including oculopharyngeal muscular dystrophy (OPMD) and hepatitis B. By combining the specificity and gene silencing effect of RNAi with gene therapy, ddRNAi has the potential to produce long-lasting silencing of disease-causing genes from a single administration, which could minimize the requirement for patients to take regular doses of medicine. Benitec’s objective is to become the leader in discovering, developing, clinically validating and commercializing ddRNAi-based therapeutics for a range of human diseases with high unmet clinical need or large patient populations and, as a result, provide a better life for patients with these diseases.

Brii Biosciences is a biotechnology company developing therapies to address major public health challenges where patients experience high unmet medical needs, limited choice and significant social stigmas. With a focus on infectious and central nervous system diseases, we have built a robust pipeline of potential treatment options based on patient insights and experiences, and are advancing these differentiated investigational therapies to address patient choice. Led by a visionary and experienced leadership team, Brii Bio has deep scientific expertise and a proven ability to progress therapeutic assets from discovery to commercial approval on a consolidated timeline. Established in 2018, Brii Bio now has operations in key biotech hubs, including Raleigh-Durham, the San Francisco Bay Area, Beijing and Shanghai. On July 13, 2021, the Company was officially listed on the Hong Kong Stock Exchange under the stock code 2137.HK.

Maintaining musculoskeletal health is the keystone of overall health as we get older. As we age our physical condition gradually deteriorates, leading to loss of strength, fitness and mobility. In most cases, this isn’t due to a simple decision to stop exercising. It is due to the breakdown of musculoskeletal function caused by disease. Musculoskeletal diseases such as osteoarthritis, tendinopathy and lower back pain are the primary causes of disability and early retirement in people over the age of 65. Currently, there are no approved disease-modifying drugs for these diseases, meaning that physical decline in old age is inevitable. At Causeway, we believe that physical decline in old age is not inevitable and in indeed may be reversible. To address this, we are developing a range of therapies that treat common MSK diseases that will allow us to remain fit and active into our nineties and beyond. Staying active as we get older also reduces the risk of developing osteoporosis, dementia, diabetes, obesity, cancer and cardiovascular disease.

Leuko is developing the first non-invasive white blood cell device. White blood cell assessment is a first-line indicator for various medically-relevant situations, ranging from chemotherapy management to the detection of life threatening infections worldwide. This test is currently invasive and not readily accessible - it requires patient travel, blood draws and laboratory infrastructure. Based on MIT research, Leuko is re-imagining the way to perform these tests without extracting blood and in a portable device.

Established in 2007, Suzhou Ribo Life Science Co., Ltd. (Ribo) is a clinical stage company devoted to the development of innovative RNAi technologies and oligonucleotide therapeutics as an effort to address unmet clinical needs in the world with the tools, capacity and RNA therapeutics that we build up in China. Fueled by our mission to make China's oligonucleotide therapeutics serve the world, we seek. Based on its cutting edge RNAi technologies, Ribo has established oligonucleotide therapeutic platform that vertically integrates the complete set of technologies to support the full life cycle of oligonucleotide therapeutics from early R&D to commercialization.

TransCode's lofty goal is delivering a cancer-free future for all cancer patients. Our core belief is that cancer can be overcome through the intelligent design and efficient delivery of targeted therapeutics. Our lead therapeutic candidate, TTX-MC138, targets microRNA-10b, or miRNA-10b, considered the master regulator of metastatic cell viability in a range of cancers, including breast, pancreatic, ovarian, colon cancer, glioblastomas, and several others. Our other preclinical programs include two solid tumor programs, TTX-siPDL1, an siRNA-based modulator of programmed death-ligand 1, or PD-L1, and TTX-siLIN28B, an siRNA-based inhibitor of RNA-binding protein LIN28B. TransCode also has three cancer agnostic programs, TTX-RIGA, an RNA- based agonist of the retinoic acid-inducible gene I, or RIG-I, targeting activation of innate immunity in the tumor microenvironment; TTX-CRISPR, a CRISPR/Cas9-based therapy platform for the repair or elimination of cancer-causing genes inside tumor cells; and TTX-mRNA, an mRNA-based platform for the development of cancer vaccines that activate cytotoxic immune responses against tumor cells. Until now, targeting biomarkers that are the primary drivers of cancer onset, progression and recurrence have been locked behind the challenge of delivery – cytosolic delivery to engage these known targets. TransCode believes it has overcome this barrier, opening the door to a broad array of cancer therapies -- a disease with the highest unmet need that affects everyone. It is through the design and optimization of this technology that TransCode has devised an elegant solution -- TTX -- a proprietary delivery platform for the transport of targeted therapeutics to cancer cells. With their world class team and know how, TransCode has a rapidly expanding platform of drug candidates designed to target a variety of tumor indications with the goal of long-term treatment survival.

Treadwell Therapeutics is a clinical-stage biotechnology company developing novel therapeutics for highly aggressive cancers by targeting critical tumor-specific vulnerabilities including aneuploidy and immunogenicity. The Company’s robust, internally developed pipeline includes novel small molecule drugs in single agent and combination studies. Lead candidate, CFI-400945, is a PLK4 inhibitor in multiple Phase 1 and Phase 2 trials including for TNBC, prostate cancer and AML. Additional product candidates include CFI-402257, a clinical stage TTK inhibitor, as well as CFI-402411, a preclinical HPK1 inhibitor (IND filing 1H20), which is positioned to be the first clinical stage small molecule modulator of a unique node of T cell activation and has a mechanism distinct from PD1/PDL1.