Wave Life Sciences

But as it relates to AATD, obviously, for the Phase 1 study and Phase 1/2, our goal will be to establish dose frequency, like we have done for others, driven primarily on the plasma biomarkers. So we’re going to have the opportunity, I think, to do two things. One is validation of editing in the production of protein, and to see how that correlates, again, with our preclinical data. That data again, as Wave Life Sciences Ltd we shared on the call, I think serves two purposes. One, obviously incredibly exciting for the alpha-1 community in terms of advancing a therapeutic program and designing a program for both lung and liver. We’ll also be looking at biopsies, that important point to the study of liver and editing. In an initial data analysis, single doses of WVE-003 up to 90 mg appeared generally safe and well-tolerated.

WVE-N531 (PN-modified splicing oligonucleotide) for DMD is being evaluated in an open-label, intra-patient dose escalation clinical trial . Dose escalation is complete and multi-dosing is underway with three 10 mg/kg doses of WVE-N531 every other week, to be followed by planned muscle biopsies. Clinical biomarker and safety data is expected in the fourth quarter of 2022. Possible cohort expansion will be informed by an assessment of the concentration and distribution of WVE-N531 in muscle tissue, as well as biomarkers, including exon skipping and dystrophin. “These findings provide a powerful demonstration of Wave’s stereopure oligonucleotide platform and its potential to rationally design therapies targeting currently untreatable genetic conditions,” said Greg Verdine, founder, board member of Wave Life Sciences. But I mean, what’s exciting for us is it is a consequential indication we have and one only needs to look at some of the programs that have face challenges to see kind of what’s the market reaction to that.

Revenue

Recently, we have generated multiple proof-of-concept datasets that demonstrate how AIMer can activate gene pathways by modulating Protein-Protein interactions, and upregulate RNA expression by editing RNA binding protein motifs. These applications demonstrate the potential to design therapeutics to precisely control gene upregulation by titrating, RNA editing levels and AIMer dose. In the second quarter we shared data using one of our lead AATD AIMer to restore functional AATD protein. At 19 weeks restored AAT protein was determined to be functional as measured by robust inhibition of neutrophil elastase as well as past the staining of liver biopsies demonstrating reduced accumulation of Z-AAT aggregates over the duration of the study. The selection of 006 to take forward into IND enabling toxicology studies followed a thorough evaluation of multiple lead compounds, each with potent editing capability in preclinical studies in mice and non-human primates in order to choose the molecule with the best overall profile.

On the right hand side of slide 10, you can see some preliminary pharmacokinetic data from this study compared with data from Suvodirsen, our first generation PSPO compounds. The figure shows plasma concentrations following single doses of N531 at three dose levels compare with the top dose of Suvodirsen used in our discontinued Phase 2/3 study.

WaVe Life Sciences Competitors (

Wave Life Sciences is developing suvodirsen for the treatment of Duchenne muscular dystrophy , a progressive muscle-wasting disease caused by the lack of a protein called dystrophin that acts as protective sheathing between muscle fibers. During an interim assessment, investigators compared levels of dystrophin found in sample muscle tissue taken before and after treatment. Sadly, suvodirsen failed to make a meaningful difference in dystrophin levels. And then secondly, that really does unlock for us and once we’ve established that preclinical to clinical translation, opens up modeling for us to be thinking much more broadly.

• There were no meaningful changes in clinical outcome measures, although the dataset and duration were not sufficient to assess clinical effects.
• Dose escalation is complete and multi-dosing is underway with three 10 mg/kg doses of WVE-N531 every other week, to be followed by planned muscle biopsies.
• Clinical data expected in 2022 for WVE-003 to provide further insight into the clinical effects of PN chemistry and enable decision-making for this program.
• What are the efficacy endpoint that you will be focused on in order to potentially capture benefits for both liver and lungs?
• The figure shows plasma concentrations following single doses of N531 at three dose levels compare with the top dose of Suvodirsen used in our discontinued Phase 2/3 study.
• Wave reported a net loss of $39.0 million in the third quarter of 2022, as compared to $6.2 million in the same period in 2021.

Takeda handed Wave $110 million up front in 2018 for options to co-develop and co-commercialize candidates aimed at Alzheimer’s and Parkinson’s disease. A lack of efficacy in a lead drug candidate is not what investors were expecting. And I’m grateful to every Wave employees for their dedication and unrelenting focus on our mission, and all the patients and families we serve. So in the mouse model, we’re using the mouse endogenous data.

WaVe Life Sciences Recent Patent Activity

Wave did not record any revenue under the Takeda Collaboration in the first quarter of 2021. Founded in 1993 by brothers Tom and David Gardner, The Motley Fool helps millions of people attain financial freedom through our website, podcasts, books, newspaper column, radio show, and premium investing services.

It also includes bioengineered tissues used for in vitro testing (e.g. organ-on-a-chip, organoids). An open-label extension trial for participants in the FOCUS-C9 trial was initiated in the fourth quarter of 2022. Revenue earned during the three months ended September 30, 2021 was $36.4 million, as compared to $3.4 million for the three months ended September https://www.wave-accounting.net/ 30, 2020. PitchBook’s non-financial metrics help you gauge a company’s traction and growth using web presence and social reach. Please enable JavaScript or switch to a supported browser to continue using twitter.com. You can see a list of supported browsers in our Help Center. This website is using a security service to protect itself from online attacks.

HD causes nerve cells in the brain to deteriorate over time, affecting thinking ability, emotions, and movement. HD is caused by an expanded cytosine-adenine-guanine triplet repeat in the huntingtin gene that results in production of mutant HTT protein. Accumulation of mHTT causes progressive loss of neurons in the brain. Wild-type, or healthy, HTT protein is critical for neuronal function and suppression may have detrimental long-term consequences.

Wave’s researchers synthesized rationally designed stereopure isomers of mipomersen, an FDA approved drug comprised of 524,288 stereoisomers. These researchers demonstrated that phosphorothioate stereochemistry substantially impacts the pharmacologic properties of ASOs. Furthermore, their work identified a stereochemical code that can be rationally designed in the stereopure ASOs that promotes targeted RNA cleavage by RNase H1, and that provides a more durable response in mice than is achieved by stereorandom ASOs. Wave’s research also demonstrated that this stereochemical code improved pharmacologic properties both with mipomersen and with a second sequence that targets APOC3. This stereochemical platform provides a foundation for Wave’s current pre-clinical and clinical programs, including two recently initiated trials in Huntington’s disease (PRECISION-HD1 and PRECISION-HD2). Dicerna Pharmaceuticals is a pharmaceutical company developing RNA interference -based therapeutics against genetically-defined targets in multiple disease areas, including cancer. Dicerna’s therapeutic approach utilizes its Dicer Substrate siRNA molecules and EnCore drug delivery technologies to silence previously undruggable disease targets, offering a potential new treatment option for patients.