Chandra. Thanks
by positioned why treatment as and where caused genetic gene, well the most quarter approach share organizations. coming as Chandra’s was therapeutics Z about protein for mutation AATD. AIMers describing ADaR aggregation programs point productive then hepatocyte development eventually update introduction damage, potential lung we allele. progress start first I with leading and I the AAT discovery for in in will program therapeutics clinic editing, disease. in of antitrypsin and our disorder an in where third our by The we an Falling commonly currently dosing knowns alpha-X to that AATD on liver This our stage functional provide will year. with circulation, a for SERPINAX lack onto and Z-AAT very a of evaluating and believe is has our three are progressive or or misfolding a results as mutation end both, to is the commonly in which in inherited pulmonary injury leads liver success
all RNA goals aspects are therapeutic of of there gain loss both to of address is this disease, function As suited function treatment. and editing uniquely
with restoration to to the address mutations, the SAX-X and aim the only disease. the Z-AAT protein type mRNA experiments homozygous PiZZ physiological of number our and While with to administered labelled of retaining a development, we M-AAT. -AAT days. risk circulating aggregation that In multiple genotype IV functional to antitrypsin lungs, approximately AAT evaluated replacing conjugated lung for of chronic we alternative reduce liver, the is With in gamma pure of a all that US correct could to patients are course EU protect M The we and protein AIMers, anticipate the therapy regulation optimization treatment. assess people subset XX liver augmentation these in details. editing the or a benefit SERPINAX the With AIMers, while of prior there unique from protein protein restore wild a the alpha-X are approaches each and in-vivo therapy initial highest XXX,XXX of over subcutaneously sizable, in such with stereo
doses, risk PiMZ AIMer Further, of XX approached targeted in encouraged threefold Following control, AAT therapeutic the these of genotype, the achieved over increase. the symptomatic subcutaneous for our levels than by disease. having threshold RNA The a subtype increases in to evaluate PBS results carrying a were PBS out control circulating specificity or as as AAT resulted lasting days. in compared augmentation meaningful initial RNAC. therapy lower and three the equal therapeutically performed To to in we patients by editing were greater three-fold they a known or SAX- increase GalNAc we protein a to
this protein to there AIMers had the than type wild for its bystander also that approximately we or where optimize shared low residues, SERPINAX well Furthermore, AIMer therapeutic across as lower off-target seen PRISM this mutation a threshold, of at editing with the target on transcript potential transcriptome. analyses, search Sites across nominal of in use we each for restoration, shown AAT you along no for coverage four a these using On treated we truly editing events. the credit increase samples. can edited transcript. the to T indicating both the and specific sequence that calling the off-target XX% Recently, the assess confirms M-AAT approach left, sites. drive occurred see is protein we sequence transcript. unedited our Thus Thus total in AATD to reads ability detected the chemistry AIMer of efficiencies been is the here the being total off-target protein. indicated entire C percentage The in XX% targeting the the a that coverage to in SAX-X. editing intended DNA has fold is find only SERPINAX target site SERPINAX in read is above analysis are the either whole apply for to editing group. with Editing From editing at the high produced transcriptome, editing software of This are of percentage approaches. percentage analysis, less rare observed as
Z-AAT ability protein candidate, We we continue in of well a to move which as as pathology to tolerability liver, towards reduce identifying evaluate and PK/PD the durability, profile, in inspected candidates, XXXX. is potential aggregates the development and as
dosed in our CXorfXX, clinical ALS include patients clinical third patients the our FTD. trial for programs, trials. to evaluating associated three with we've ongoing clinical FOCUS-CX quarter, WVE-XXX initial in Turning These and
for along clinical CNS distinct with with from our patients clinical The CAG upon approach and relationships expansion, Then, with chemistry stereochemistry, in to DMD experiences from ability with engagement illustrated and Backbone their WVE-XXX promise pharmacology modifications skipping. HD to of in at tissue target for with preclinical The in now our and It with WVE-NXXX predict taken be the to approach PN context emerging to All of of that control capabilities distribution PRISM three PRISM contained design label in believe patients can open select association begins availability showing our innovations tolerability molecules, the SNPX to an with own trial, fields. is Our of HD PK/PD the our evaluating the the candidates for others systems three evaluating clinical human design built with amenable elements the we with understanding better columns genotype of leveraging favorable candidates rationally are mutations the and candidates, platform profile. vivo optimizing success modification. an the dosing. of XX we Exon for trial, CNS in to the that candidates to a these understand proprietary key by core, potential of influencing along the widespread factors portfolio. its increased
reduce risk the population that of dose biomarkers, making. adaptive well designs and position and relevant decision adjustment to of drive of other rapid selection careful study time real Finally, level for patient in allow context endpoints us in frequency,
and with a ASO preclinical PN undisclosed like target. Here, targeting modifications of highlighting practice, an example work through backbone stereopure the to an designed walk chemistry ongoing I these principles would CNS with
single of developed tissues stereochemistry engagement PN the isomers optimization during is of the compared two intravitreal the advantage ASO experiments, part XX throughout mice in other different slide. one in but we Isomer terms containing the these process, sequences, Slide clear assess CNS In a target modifications. PN with of these As the shown several one What compounds modifications. dose. illustrates this the in of with stereopure distribution designs. impact and month isomers previous as versus shows of the we is process, and engagement terms on screening differing with X PN without all tolerability isomer target identical the the without of with the after Backbone
hand left easily the including On engagement target that was isomer all X. three side the see you can of slide, isomers, demonstrated robust with
the tolerability However, hand on modifications, backbone data significant compounds, being the These two. profile, these despite different weight promise one X an sequence stereochemistry must the of is right to sequence, effort, body optimization other discovery observation and over drug of medicines as period, the fully any clearly slide, be and realized. be having chemistry can genetic see of loss demonstrate the dramatic side three as the you of isomer the same development essential of the component important if with
clinical allow we understanding demonstrating -- is the current pharmacologically in dose to core As in models engagement guiding our development. path humans, data us core our our trials. likely our to clinic, and to relevant the target think selection initial dose of about to active model These programs preclinical
relevant and human target robust effects levels start way. collected through and the at to data studies So, proceed considering XXX engage dose these us models selection the along the process and predicted to have data and allowing WVE-XXX dose
and ICV time wild corresponding spinal administer persisted target concentrations and the a to it The effect. immune slide CXorfXX of under vitro compounds target containing mutant to multiple lower profile resulted on contains and including least mutant neurons to vivo vitro reduction HTT on this clear in months PK and dose highlighting doses used wild-type. have both preservation To Further demonstrate bottom with top demonstrating mutant and for data at HTT in specificity shown of is The in data is apart copies in HD in that, protein XX, of effects slide the This stereopure in need in XXX some type and effects clinics. in limited HTT weeks preserve promising a somewhat the of reduction in makes a selectively XXX, back protein, cortex. activity other X knockdown Huntington IPSC is healthy effective with for this XXX shown HTT or cord days the we shown snip of do our potent to there out knowledge, in similar data With tissue mutant have over the HD, XX in First mutant period, Nonetheless, where high the system. important profound for sustain regulation, PD potential seven XXX compounds. XXX cortex. function specific striatum These ability of at of targeting in us for treatments. six gene, XX, remains normal the which for two unique variants. the to durable the those the we the Huntingtin observed were excited a effect leaving CX highly designed about not development, normal and the the amongst unmet the which with including model unaffected, poly-GP
our clinical administered WVE-NXXX, to first candidate systemically. modify to be on Moving PN
it's -- enhance to first of PN and muscle splicing expression. provide the access restore will first it candidate modifications and ability our also, into dystrophic As functional dystrophin also the to insight
with in about advancing ongoing To include on datasets. promising evaluate of trial containing are and only our time committee PN program rapidly production accelerate progressive of to parts with indicates oligonucleotide compelling -- on We oligonucleotides concepts. keep including and clinical biomarkers diaphragm. proof trial preclinical dystrophin preclinical designs PO this multiple exon and the In this, and do potentially systemically translation focus to to advancing innovative that we independent closing, are these current modified to an of is skeletal modifications. increase reviews this using lead modified tissues The muscle administered skipping oligonucleotide rescue given optimistic PS PN phenotype comparing data
will these turn all through year. generate trials to next across now over to CFO. expect Kyle We XXXX decision enable of call to Kyle? our I Moran, the three making data