Shape Therapeutics, Inc.

AIRNA’s total capital raised so far is $245m. Credit: sesame via Getty Images. AIRNA has raised $155m in Series B financing to advance its RNA editing pipeline, and kick-start a clinical trial for its lead candidate, AIR-001. Venrock Healthcare Capital Partners and Forbion Growth co-led the new round, bringing AIRNA’s total raised capital to $245m. The US and Germany-based biotech plans to file a clinical trial application (CTA) for its lead candidate, AIR-001, for alpha-1 antitrypsin deficiency (AATD) by H2 2025. The company is developing AIR-001 as an investigational RNA editor – a therapy designed to modify RNA sequences to correct disease-causing mutations. This approach is different to DNA editing approaches such as clustered regularly interspaced short palindromic repeats (CRISPR), which make permanent changes to the genome. RNA editing is a reversible process that allows for targeted corrections without altering the underlying genetic code. The Series B funds will support the launch of a Phase I/II clinical trial for AIR-001 and the further development of other RNA-editing candidates, primarily targeting cardiometabolic diseases. AATD is a rare genetic disorder caused by mutations in the SERPINA1 gene, which encodes the AAT protein. Under normal circumstances, AAT is produced in the liver and transported to the lungs, where it regulates enzyme activity to prevent tissue damage. In patients with AATD, mutations can prevent AAT from exiting the liver, leading to toxic protein accumulation that damages the liver while also depriving the lungs of necessary protection. This can result in progressive lung disease, liver dysfunction, and symptoms such as shortness of breath, fatigue, and jaundice. The AATD treatment landscape is becoming increasingly competitive as multiple biotechs advance RNA-editing candidates. Korro Bio is investigating its candidate KRRO-110 in the Phase I/IIa REWRITE clinical trial (NCT06677307), with interim data expected in H2 2025. The company announced last month that the dosing of the first two cohorts had been completed, and the trial is expected to conclude next year. Wave Life Sciences is developing WVE-006, which demonstrated targeted RNA editing in the first two patients treated in the Phase Ib/IIa RestorAATion-2 clinical trial (NCT06405633). The growing interest in RNA editing has also drawn investment from major pharmaceutical companies. In November 2023, Roche expanded its partnership to develop a one-time RNA editing therapy using ShapeTX’s AI-powered platform for an undisclosed disease. In September 2024, Novo Nordisk and Korro Bio announced a collaboration leveraging Korro’s OPERA platform to enable oligonucleotide-directed RNA edits for two undisclosed targets, initially focused on cardiometabolic diseases. The deal included up to $530m in upfront, development, and commercial milestone payments, along with tiered royalties and R&D funding. Not all genetic medicine approaches for AATD have progressed as planned. In January 2025, Intellia Therapeutics discontinued the development of its CRISPR-based gene therapy NTLA-3001, which was intended to correct the SERPINA1 mutation at the DNA level. Preparations for the Phase I/II trial were halted, along with other early-stage programmes, signalling a shift in the company’s pipeline priorities. With fresh funding and a CTA planned for later this year, AIRNA is positioning itself within the growing RNA editing field. Forbion managing partner Dirk Kersten said: “AIRNA’s innovative approach to RNA editing has the distinctive potential to improve health across large populations by introducing healthy genetic variants for many conditions. We are excited to support the expansion of AIRNA’s pipeline of life-changing medicines and the advancement of AIR-001 into the clinic.”

Dive Brief:Airna, a biotechnology startup developing RNA editing treatments, said Tuesday it raised $155 million in a Series B round that will help propel its lead program in alpha-1 antitrypsin deficiency into the clinic later this year.That medicine, codenamed AIR-001, repairs faulty RNA transcribed by the gene thats mutated in alpha-1 antitrypsin deficiency, or AATD. When the RNA is edited, cells are able to produce functional copies of AAT protein, lowering the risk of associated lung and liver disease.Airnas raise comes nearly six months after Wave Life Sciences unveiled promising Phase 1 data for an RNA editing drug also aimed at AATD. Similar to Wave, Airnas drug uses a sugar molecule to take its medicine into the liver.Dive Insight:No cure currently exists for AATD, which in some patients is managed with weekly injections of AAT protein. Airna estimates approximately 100,000 people in the U.S. have AATD.Co-founded by professors Thorsten Stafforst at the University of Tubingen and Jin Billy Li at Stanford University, Airna hopes to fill that niche with technology that can recruit an enzyme known as adenosine deaminase acting on RNA, or ADAR, to modify RNA.Kris Elverum, Airnas CEO, said the appeal of a drug like AIR-001 is its resemblance to biologic drugs, rather than experimental gene therapies that permanently alter DNA and can be costly to manufacture. AIR-001 is administered via a subcutaneous injection and its developers are experimenting with how to maintain its potency at lower dosages.Patients and physicians want to be able to have options that can give them a functional cure while maintaining flexibility and control over their healthcare decisions, Elverum said.The company has not disclosed specific conditions its targeting outside of AATD, but co-founder Stafforst has published research on the applicability of RNA editing in cardiometabolic and neurodegenerative diseases.RNA editing is not going to be the solution for every disease and every target, but what our data suggests is that the physiological effects of healthy variants that we identify can be reproduced through a single RNA edit, Elverum said.The Series B round was co-led by Venrock and Forbion, and included investors such as RTW Investments, Arch Venture Partners and Nextech Invest. Airna previously raised $90 million after emerging from stealth in 2023.Startups such as Shape Therapeutics, Ascidian Therapeutics and ADARx Pharmaceuticals, as well as established biotechs such as Wave and Korro Bio, have turned to RNA editing for tough-to-treat diseases. While the field has drawn hundreds of millions of venture capital dollars and the attention of pharma partners such as Roche and Novo Nordisk, its unclear whether any drugs resulting from that investment will succeed in finding a treatment niche.Airnas innovative approach to RNA editing has the distinctive potential to improve health across large populations by introducing healthy genetic variants for many conditions, Derk Kersten, a managing partner at Forbion, said in a statement. '

Company's DeepREAD AI model and small RNA expression system represent major leaps forward in RNA editing efficiency and specificity Generative AI model, trained on millions of experimental datapoints, for the first time enables efficient design of ADAR guide RNAs for any target Enhanced U7 SmOPT expression system dramatically increases RNA editing efficiency at gene therapy-relevant dose levels SEATTLE, Oct. 03, 2024 (GLOBE NEWSWIRE) -- Shape Therapeutics, a leader in RNA-based gene therapy, today released two preprint manuscripts detailing major technological breakthroughs that underpin the company's therapeutic editing platform RNAfix®. RNAfix® uses engineered guide RNAs (gRNAs) delivered by Adeno-Associated Virus (AAV) to recruit the natural ADAR enzyme and enable editing of target sites in a patient’s RNA. These new advances overcome longstanding challenges to harnessing ADAR for therapeutic RNA editing, positioning ShapeTX at the forefront of programmable RNA medicines. The first manuscript, "Generative Machine Learning of ADAR Substrates for Precise and Efficient RNA Editing," introduces DeepREAD (Deep learning for RNA Editing by ADAR Design), one of Shape's custom AI models for gRNA design. Trained on data from high-throughput screens of millions of RNA sequences, DeepREAD generates gRNAs that form highly engineered structures when bound to target RNA. These novel structures redirect ADAR's natural sequence preferences, enabling specific and efficient editing of virtually any target adenosine. "DeepREAD represents a significant advancement in RNA editing gRNA design," said Ron Hause, Ph.D., SVP and Head of AI at Shape Therapeutics. "Our diffusion-based model generates highly efficient and specific guide RNAs for any adenosine in the transcriptome over 10,000 times faster than previous methods, rapidly producing thousands of high quality designs in minutes that outperform existing heuristic design approaches. This dramatically accelerates the development of RNA editing therapeutics for a wide range of genetic disorders." The second manuscript, "A Novel Engineered U7 Small Nuclear RNA Scaffold Greatly Increases in vitro and in vivo ADAR-Mediated Programmable RNA Base Editing," provides a detailed look at Shape's advanced system for expressing therapeutic gRNAs inside patient cells. By borrowing principles from natural small RNAs and performing deep profiling and additional engineering to enhance efficiency, Shape’s novel scaffold drives high expression of gRNAs at the precise sites in a cell where ADAR activity occurs, leading to unprecedented levels of RNA editing in vitro as well as in the brain of animals given a systemic injection of AAV-delivered gRNA. "Our enhanced U7 SmOPT expression system represents a huge advancement for the therapeutic application of RNA editing, particularly in areas like the central nervous system where AAV delivery is often constrained to low doses per cell," said Adrian W. Briggs, Ph.D., Chief Technology Officer at Shape Therapeutics. The advances described in the two new manuscripts provide a blueprint for a breakthrough gene therapy pipeline. “By combining AI-powered gRNA design with our optimized expression system, we can now precisely and efficiently edit RNA targets that were previously out of reach and at an efficiency unmatched by other editing platforms. This opens up exciting possibilities for treating a wide range of genetic disorders in the CNS and beyond," said Dr. Briggs. About Shape Therapeutics ShapeTX® is pioneering the field of programmable RNA medicines to repair the genetic causes of diseases. By merging innovations in AI and RNA technology to generate and analyze hundreds of billions of therapeutic possibilities, ShapeTX is developing breakthroughs in RNA editing, next-generation AAVs, and disruptive gene therapy manufacturing. The ShapeTX platform enables pharma innovators to design treatments across a wide range of diseases, including rare genetic disorders as well as debilitating conditions, such as Alzheimer's, Parkinson's, and many more. You can find us at shapetx.com and on LinkedIn and Twitter. Media Contact:info@shapetx.com