List of RNA Therapies Companies with Phase 2 Active Clinical Trial - 26

Our strategy is to develop pharmacologically optimized drug candidates, which are first assessed in healthy volunteers and patients as monotherapy prior to their use in combination regimens designed to achieve improved treatment outcomes in patients. Our initial areas of focus are viral and liver diseases where our team can leverage their in-depth knowledge and expertise to develop potentially best-in-class combination regimens for each disease area with significant unmet medical need.

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.

Founded in 2013 and based in San Diego, California, Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT) is a global mRNA medicines and vaccines company with enabling technologies: (i) LUNAR® lipid-mediated delivery, (ii) STARR® mRNA Technology (sa-mRNA) and (iii) mRNA drug substance along with drug product manufacturing expertise. Arcturus developed Kostaive®, the first self-amplifying messenger RNA (sa-mRNA) COVID vaccine in the world to be approved. Arcturus has an ongoing global collaboration for innovative mRNA vaccines with CSL Seqirus, and a joint venture in Japan, ARCALIS, focused on the manufacture of mRNA vaccines and therapeutics. Arcturus’ pipeline includes RNA therapeutic candidates to potentially treat ornithine transcarbamylase (OTC) deficiency and cystic fibrosis (CF), along with its partnered mRNA vaccine programs for SARS-CoV-2 (COVID-19) and influenza. Arcturus’ versatile RNA therapeutics platforms can be applied toward multiple types of nucleic acid medicines including messenger RNA, small interfering RNA, circular RNA, antisense RNA, self-amplifying RNA, DNA, and gene editing therapeutics. Arcturus’ technologies are covered by its extensive patent portfolio (over 400 patents and patent applications in the U.S., Europe, Japan, China, and other countries).

ARTHEx Biotech is a spin-off biotech company from the University of Valencia (Spain) focused on the research and development of novel oligonucleotide therapies that modulate microRNA to treat diseases with unmet medical needs. ARTHEx has developed its proprietary technology, the ENTRY ™ platform, that allows fast and flexible development of investigational miR-modulating oligonucleotides that are designed to enter relevant tissues in pharmacological quantities, in order to treat diseases in which microRNAs play a key role. The first investigational product from this platform is ATX-01, an antimiR in preclinical development for Myotonic Dystrophy Type 1 (DM1). DM1 is an orphan disease affecting more than 900,000 people worldwide (estimated prevalence 1/8,000) with no cure, nor approved treatment to date. ATX-01 is a first-in-class disease-modifying therapy that addresses the cause of DM1 with a dual and unique mechanism of action, which targets micro-RNA-23b a key factor in the disease pathogenesis. To learn more about Arthex Biotech, please visit us at www.arthexbiotech.com

Ascidian Therapeutics is redefining the treatment of disease by rewriting RNA. By editing exons at the RNA level, Ascidian therapies enable precise post-transcriptional editing of genes, resulting in full-length, functional proteins at the right levels, in the right cells, at the right time. With active discovery and preclinical programs in ophthalmology, neurological and neuromuscular disorders, and other rare diseases, Ascidian is opening new therapeutic possibilities for patients in need of breakthroughs.

Basking is developing the first in class agent (BB-031) targeting von Willebrand Factor (VWF) along with a direct acting reversal agent (BB-025) to immediately the pharmacological effect of BB-031 in the event of bleeding. BB-031 is an RNA aptamer optimized for rapid onset of action and short duration of effect. Basking will initiate a Phase 2 trial in acute ischemic stroke in late 2023 and is exploring further application in pulmonary embolism in preclinical studies. The technology is based on two decades of translational research on RNA aptamers as therapeutic agents for cardiovascular diseases.

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.

Capsida Biotherapeutics Inc. is an industry-leading gene therapy platform company creating a new class of targeted, non-invasive gene therapies for patients with debilitating and life-threatening genetic disorders. Capsida's technology allows for the targeted penetration of cells and organs, while limiting collateral impact on non-targeted cells and organs, especially the liver. This technology allows for the delivery of the gene therapy in a non-invasive way through intravenous administration. Capsida's technology is protected by a growing intellectual property portfolio which includes more than 30 patent applications and one issued U.S. patent 11,149,256. The company is exploring using the technology across a broad range of life-threatening genetic disorders. Its initial pipeline consists of multiple neurologic disease programs. The company has strategic collaborations with AbbVie and CRISPR, which provide independent validation of Capsida's technology and capabilities. Capsida is a multi-functional and fully integrated biotechnology company with proprietary adeno-associated virus (AAV) engineering, multi-modality cargo development and optimization, translational biology, process development and state-of-the-art manufacturing, and broad clinical development experience. Capsida's biologically driven, high-throughput AAV engineering and cargo optimization platform originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at the California Institute of Technology.

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.

enGene Inc. has developed a highly flexible nucleotide (DNA and RNAi) delivery technology that targetsmucosal tissues and can be used to treat numerous prevalent, chronic diseases via the induction or suppression of protein expression levels. Our platform technology has the ability to significantly impact diseases of mucosal tissues such as the gastrointestinal tract, lung and bladder as well as provide systemic release of proteins from the gut to treat diabetes, anemia, hemophilia and others.

Exai Bio is a next-generation liquid biopsy company. Our mission is to enable a world where cancer can be detected early, diagnosed accurately, treated in a personalized and targeted way, and ultimately cured. The company's proprietary RNA and artificial intelligence-based liquid biopsy platform delivers clinical insights into cancer biology to enable the earliest, most accurate diagnosis of cancer. Exai Bio was founded with technology from the UCSF laboratory of Dr. Hani Goodarzi, and consists of veteran leaders in the RNA biology, liquid biopsy, and artificial intelligence/machine learning fields from both academia (UCSF, Stanford, MIT) and industry (Bluestar, CareDx, Evidation, Google, 23andMe, Deep Genomics). Exai Bio is supported by leading life sciences and tech investors including Section 32, Casdin Capital, and Two Sigma Ventures, who have been integral to advancing cancer diagnostics, and artificial intelligence and machine learning technologies. We know that people are our greatest asset and we are rapidly building a rock-star team of talent. Our people are driven by the mission, inspired by the vision of the future, and are committed to living our core values (integrity, openness, teamwork, exploration, and kindness) that connect us to our work and to one another. What We Value Our core values represent what we stand for as a team. This is what we believe in. Everyday, we strive to align our behaviors to these core values in everything we do. Integrity – Our thoughts and actions are true to science and to people. We do the right thing. Openness – We recognize and respect our differences – and embrace learning from them. Teamwork – We are team players who trust and respect each other. Exploration – We are explorers, putting curiosity into action. Kindness – We are kind whenever possible – and we believe it's always possible.

Flamingo is pioneering RNA-targeted therapies for oncology with state-of-the art chemistries and a clinical-stage pipeline targeting undruggable transcription factors and splice variants. Flamingo Therapeutics has a Phase II trial (PEMDA-HN) evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, funds managed by Tekla Capital Management LLC and VIB.

Geneoscopy is a life sciences company with the mission to empower patients and providers to transform gastrointestinal health through innovative diagnostics. Geneoscopy's lead diagnostic uses stool-derived eukaryotic RNA (seRNA) to detect colorectal cancer and precancerous adenomas. This device was awarded a Breakthrough Device Designation from the FDA for its ability to reduce morbidity associated with colorectal cancer through advanced adenoma detection. Our initial prospective clinical study demonstrates that the diagnostic can detect these lesions with greater sensitivity than all existing noninvasive screening tests, thereby, serve as a potential aid in early detection and prevention of cancer. Geneoscopy is also developing diagnostics for the diagnosis and management of inflammatory bowel disease in partnership with biopharmaceutical companies and leading academic research institutions.

Gradalis is a late-stage clinical biotechnology company developing immunotherapies for multiple cancer indications including an upcoming Phase 3 registration trial in patients with ovarian cancer. The company’s proprietary bi-shRNA therapy platform, which has been proven in its clinical studies, can be utilized to silence a broad range of genes and is applicable to multiple cancer types. About Vigil Vigil® is the first cellular therapy to show positive survival benefits in a randomized controlled clinical study of patients with solid tumors. Vigil is a self-navigating cellular immunotherapy that addresses the major deficits of leading cancer treatments. Vigil uses all of a patient’s tumor-related antigens to identify cancer cells and then enhances the training of the immune system to recognize and attack those cells. Gradalis’s proprietary bi-shRNA platform accomplishes this via three key functions: (1) it blocks furin, the enzyme that generates the immunosuppressive cytokines TGF beta types 1 and 2; (2) it activates effector cells including antigen-presenting dendritic cells and CD8+ T cells via the production of GM-CSF; and (3) it induces an immune response to the full complement of neo-antigens from the patient’s tumor via intradermal administration. In a Phase 2b trial, Vigil showed a positive trend in the primary endpoint of recurrence-free survival in the overall population and a significant improvement in recurrence-free survival and overall survival in a pre-planned subgroup analysis of Stage III/IV newly diagnosed ovarian cancer patients with the BRCA wild type (BRCA-wt) molecular profile. The company is preparing to initiate a clinical study intended for product registration in patients in this subgroup. Additionally, Phase 1 results in an all-comer trial have shown positive signals of activity in multiple tumor types.

Highlight, formerly known as Bioncotech Therapeutics S.L, is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Its lead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging a unique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has the potential to rescue patients who are resistant to current checkpoint inhibitor therapy. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint inhibitors. In addition to in-house research, Highlight Therapeutics has a number of external collaborators, including Merck & Co and UCLA.

Immorna is a rapidly expanding biotechnology company, focusing on the development of mRNA-based therapeutics and vaccines. Immorna is utilizing multiple mRNA platforms, including conventional, self-replicating and circular mRNA. Since it’s founding in 2019, Immorna has built a robust CMC platform for mRNA synthesis, purification, and analytical testing that is well suited for clinical and commercial development. In addition, with its state-of-the-art screening tools, Immorna has developed an arsenal of mRNA delivery vehicles, including polymers and lipid nanoparticles featuring multiple proprietary ionizable cationic lipids suitable for intramuscular, intravenous and tissue-targeting delivery. Immorna has a growing intellectual property portfolio and a diverse mRNA development pipeline spanning cancer immunotherapy, infectious diseases, rare genetic diseases, and medical cosmetology, and quickly advancing its oncology and infectious disease drug candidates into their clinical stages.

Mirxes is a Singapore-headquartered biotechnology company whose mission is to save lives through early, actionable, and personalized diagnoses across the care continuum. We are Asia-centered, starting with Southeast Asia, and have global ambitions. We have research, development, manufacturing, and clinical diagnostic operations in Singapore, USA, Japan, and China. We have sales and distribution networks worldwide. Our flagship product is GASTROClear, the world’s first molecular blood test for early detection of gastric cancer, able to detect around 90% of patients with Stage I and II cancers. We continue to build a comprehensive cancer portfolio with early detection tests for lung and thyroid cancer (2022), colorectal and breast cancer (2023), liver and ovarian cancer (2024). We are concurrently building a precision oncology portfolio to provide clinical insights for the complete patient journey. MiRXES was spun off from A*STAR’s Bioprocessing Technology Institute in 2014 to commercialize an industry-leading qPCR-based technology for microRNA detection. Our ID3EAL discovery tool and workflow has been adopted by top academic and industry partners globally and is backed by the world’s first industry standard for microRNA-base diagnostics. Our versatile platform technology and capabilities have broad applications in the discovery of biomarkers and diagnosis of diseases. We are starting with early cancer detection, but we will also be addressing unmet clinical needs in cardiovascular, metabolic, and infectious diseases. We responded to COVID-19 by leveraging our capabilities to mass produce and distribute over 5 million units of the Fortitude COVID-19 RT-PCR test. This made-in-Singapore diagnostic test, developed by A*STAR and Tan Tock Seng Hospital, has been deployed in 13 Singapore hospitals and clinical labs and exported to over 45 countries worldwide. Post-COVID, we will leverage this network to commercialize multi-cancer early detection tests.

NeoCura is a high-tech enterprise that relies on AI technology to create an RNA technology platform and conduct R&D of innovative drugs. The company has built multi-omics big data acquisition platforms and multiple bioomics databases. It uses AI and bioinformatics technology to conduct in-depth drug target mining and fully automated drug design for innovative RNA technology platform upgrades and drug research. It has established leading R&D centers and production centers in Beijing, Shenzhen, and Guangzhou to support pipelines development, platform upgrades, and clinical demand.

Oncovir, Inc is a pharmaceutical corporation dedicated to the development of nucleic-acid-based clinical therapies for cancer, infectious, immune, and degenerative disorders. We promote Hiltonol® (poly-ICLC) as an experimental viral mimic and broad activator of innate and adaptive immunity. While initially developed as an interferon inducer, Hiltonol® has much broader biological effects in humans, including specific antiviral, immune activating, vaccine adjuvant, and antitumor actions.

RiboNova is a privately-held biopharmaceutical company based in the Lankenau Institute for Medical Research near Philadelphia, Pennsylvania. Their product pipeline includes a Phase-2 ready small molecule drug for the treatment of all forms of genetically-confirmed mitochondrial disease and a proprietary drug discovery platform that targets transfer RNA with novel precision medicines for the treatment of mitochondrial and other diseases.

Scipher Medicine is building the future of patient treatment. Most patients who are prescribed blockbuster therapies today don’t respond to the treatment, costing the health care industry billions in wasted drugs while patients continue to suffer. Scipher's platform identifies which drug will work based on the patient's fundamental disease biology, and not based on symptoms, disease classification, or medical bias. A simple test predicts which drug he/she will respond to, ensuring that most optimal treatment is prescribed from day one. The molecular data generated by our tests is then used to fuel novel target discovery to address a clear unmet medical need in patients who do not respond to any existing therapy.

Starna Therapeutics focuses on extrahepatic targeted delivery technology and is committed to developing innovative drugs with RNA as the core to solve unmet clinical needs. The core team comes from well-known pharmaceutical companies, universities and research institutes. The team has profound capabilities in nucleic acid drug discovery, delivery technology and formulation development.

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.

Versameb AG is a privately held biotechnology company focusing on discovering and developing innovative RNA-based drugs for modulation of protein expression, including the ability to simultaneously influence several therapeutic targets, in a controlled manner, with one molecular construct, and cellular targeting. Based in Basel and fully operational from 2018, the company is led by an experienced scientific and leadership team with proven expertise in drug discovery and development from lab bench to patient. Versameb’s proprietary technology platform, VERSagile, optimizes the application of functional RNA in different disease contexts – making RNA druggable in new therapeutic areas others have been unable to solve. The pipeline includes lead candidate programs in Stress Urinary Incontinence (SUI) and solid tumors. Versameb is working towards the completion of a first in-human/proof-of-concept clinical study while advancing its platform.