RestorAATion: The First Clinical
Program Evaluating an RNA Editing
Therapeutic in Humans
Cynthia Caracta, MD
June 20, 2024
Forward-looking statements
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Wave is building the leading RNA medicines company, with RNA editing as a core competency
Multi-modal drug discovery and | Differentiated RNA medicines pipeline |
development platform |
- Therapeutic candidates that optimally address disease biology
- Clinical data updates expected in 2024 from AATD, DMD, HD clinical programs
• | RNA editing, siRNA, splicing, antisense | • | INHBE clinical trial initiation for obesity expected 1Q 2025 |
• | Best-in-class oligonucleotide chemistry | • | Initiated first-ever clinical trial in RNA editing for AATD |
Strategic collaborations | In-house GMP manufacturing | Strong and broad IP |
(GSK and Takeda) | ||
Well capitalized with cash runway into 4Q 2025*
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*Cash runway does not include potential future milestones or opt-in payments under GSK and Takeda collaborations AATD: Alpha-1 antitrypsin deficiency, DMD: Duchenne muscular dystrophy, HD: Huntington's disease
Wave's versatile multimodal RNA medicines platform is ideal for capitalizing on new genetic insights in rare and common diseases
Accessing UK Biobank and building proprietary machine learning models to generate unique genetic insights
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Claussnitzer, et al. Nature (2020) 577, 179; King et al. PLoS Genet (2019) 15, e1008489
Wave's A-to-I RNA editing oligonucleotides (AIMers)
Best-in-class, proprietary chemistry yielding superior potency, distribution, durability
Efficient and highly specific recruitment of ADAR enzymes
Uses GalNAc in the liver and free uptake outside liver; avoids LNPs/other complex delivery vehicles
Leveraging ML, AI, large genetic datasets to identify novel insights, targets, target sites
First RNA editing clinical candidate will provide proof-of-mechanism for Wave's other AIMer programs
Proof-of-mechanism data from first-ever RNA editing clinical program (RestorAATion) expected in 2024
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LNPs: lipid nanoparticles; ML: Machine learning; AI: artificial intelligence
WVE-006: A first-in-class investigational RNA editing therapeutic for AATD
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AATD may result in lung and liver disease and has limited treatment options
- SERPINA1 Z mutation (E342K) is most common cause of AATD1
- ~200,000 Pi*ZZ patients in US and Europe2
- Augmentation therapy is only treatment option for AATD lung disease and requires weekly IV infusions
- No treatment for AATD liver disease, other than liver transplant
- Average age of diagnosis of AATD lung disease is 46 years3 and average age of adult-onset liver disease is 61 years4
AATD Lung Disease | AATD Liver Disease | |||
• | Emphysema | • | Hepatitis | |
• | Asthma | • | Fibrosis | |
• | Bronchitis | • | Cirrhosis | |
• | Pneumonia | • | HCC | |
• | Bronchiectasis | • | Liver Failure | |
Other Complications
- Panniculitis (skin)
- ANCA vasculitis
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1. Greene, C.M., et al., 2016 Nat Rev Dis Primers 2, 16051; 2. Blanco et al., 2017 Int J Chron Obstruct Pulmon Dis 12:561-69; 3. Strnad, et al. 2020 N Engl J Med 382:1443-55; 4. Tanash and Piitulainen 2019 J Gastroenterol 54:541-548
Patient insights highlight burden of AATD
- It's an invisible disease. It seems like it tricks you - I look healthy and then I tell someone I can't help them grab something 20 feet away. That's the disconnect.
- I used to own a salon and with my lungs going bad so quickly, I had to do away with that…I get short winded…I lay around a lot, I'm sick a lot.
- It makes it harder for us to travel and go do things, because I have to be home once a week for my infusions. It's definitely an inconvenience.
- I now have very high elevated liver enzymes and fatty liver just in the last year. I get a lot of pain on that side. They believe it is related to AATD.
- I have back issues, anytime they do a CAT scan or MRI there is always a notation about fatty liver disease and scarring on my liver. I know it's there. I know there's a problem. It's just part of my everyday.
Engaged patient community to inform clinical development plans
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AATD landscape is poised to evolve but most approaches focus on lung or liver disease
Selected Therapeutic Strategies in Development for AATD
Frequency of Lung or Liver Disease of Pi*ZZ Patients at Diagnosis*
- Augmentation therapy (Plasma derived, IV) [Approved]
• | Recombinant Fc-AAT (IV) | Lung Disease | Liver | ||
61% | 20% | Disease | • RNAi (subcutaneous) | ||
• | Inhaled AAT (nebulized) | 5% | |||
- Neutrophil elastase inhibitors (oral)
*From Alpha One International Registry (n=3,405)3 (13% reported no disease at diagnosis)
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Despite being a rare disease, AATD market estimated to grow to ~$3B by 2028
AATD Market Overview | Global AATD Market Value (2021 - 2028)1 |
• AATD market today is estimated at ~$1.3B | $3B | |||||||
worldwide1 despite limitations of current | ||||||||
treatment | 12% | |||||||
- Market consists entirely of plasma-derived | CAGR | |||||||
augmentation therapy for AATD-lung disease | $2B | |||||||
- Augmentation therapy requires weekly IV and is not | Driven by new therapies | |||||||
reimbursed in some markets | and higher diagnosis rates | |||||||
• Market expected to grow to ~$3B by 2028 | $1B | |||||||
- Treatment for AATD-liver disease in development | ||||||||
- Opportunity to improve upon treatments for AATD-lung | ||||||||
disease (efficacy, administration) | $0B | |||||||
- Potential to increase diagnosis (e.g., for liver disease, | ||||||||
2021 | 2022 | 2023 | 2024 | 2025 | 2026 | 2027 | 2028 | |
through direct-to-consumer genetic testing) | ||||||||
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1. Evaluate Pharma; 2. Lumanity KOL Market Research 2022
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Wave Life Sciences Ltd. published this content on 21 June 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 21 June 2024 02:54:06 UTC.