Q3 2021 Sarepta Therapeutics Inc Earnings Call
[music].
Good afternoon, ladies and gentlemen, and welcome to the <unk> Therapeutics third quarter 2021 earnings call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one.
On your telephone.
A reminder, today's program is being recorded at this time I'll turn the call over to Mary Jenkins Senior manager Investor Relations. Please go ahead.
Thank you Tina and thank you all for joining today's call.
Today, we released our financial results for the third quarter of 2000 22021. The press release is available on our website at <unk> Dot Com and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon.
Joining us on the call today are Doug Ingram and at this time.
Alan Murray, Dr. Gilmore O'neill and Dr. Louise Rodino playback after our formal remarks, we'll open the call for Q&A.
Note that during the call we will be making a number of forward looking statements. Please take a moment to review our slide on the webcast, which contains our forward looking statements. These forward looking statements involve risks and uncertainties many of which are beyond <unk> control actual results could materially differ.
From these forward looking statements and any such risks can materially and adversely affect the business the results of operations and trading prices for <unk> common stock.
For a detailed description of applicable risks and uncertainties. We encourage you to review the company's most recent quarterly report on Form 10-Q filed with the SEC as well as the company's other SEC filings.
<unk> does not undertake any obligation to publicly update its forward looking statements, including any financial projections provided today based on subsequent events or circumstances.
And now I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress Doug.
Thank you Mary good afternoon, everyone and thank you for joining <unk> therapeutics third quarter 2021 financial results.
Since call.
I am pleased to report another quarter of strong and consistent performance as we continue to hit our milestones and report positive data readouts across our multi platform portfolio.
Starting with our quarterly performance, serving the Duchenne community with our three approved RNA based therapies revenue once again exceeded guidance and our second quarter call. We raised our full year net product revenue guidance by $30 million to a range of $565 million to $570 million.
We have over performed to that guidance and exceeded analyst estimates with net product revenue standing at $166 9 million for the third quarter, that's a 37% increase over the same quarter last year.
As we have never taken a price increase for our therapies and have priced all of our therapies at parity or revenue beat comes entirely from the team's ability to serve the duchenne community.
And for the benefit our therapies provide.
The lives of the Duchenne.
As I've mentioned before even during the most difficult periods of the pandemic the adherent adherence rates for our therapies.
It remained well above 90% percent speaking to the value of our therapies to those living with Duchenne.
Based on our over performance, we have once again increased our full year net product revenue guidance, our new guidance for full year 2021 is in a range of 605 to.
$615 million.
A $40 million above our previous guidance $70 million above our initial guidance this year and representing at the midpoint.
A 34% growth over the prior year.
Our performance this quarter represents our 20 consecutive quarter of positive growth and based on our updated revenue guidance for 2021, we will have a compounded annual growth of 40%.
Full year 2017.
The end of 2021.
We anticipate this strong growth to continue in 2022, our chief commercial officer.
Alan Murray will comment further on performance in a moment.
Having recently completed an equity raise bolstering our bolstering our cash position by approximately $550 million, we stand in a strong financial position to fund our pipeline successes with over $2 billion of cash and cash equivalents currently on our balance sheet augmented with strong.
Product revenue.
With our cross platform successes. This year, we are fortunate to be well funded.
Where we stand as we track out of 2021.
Starting with our gene therapy programs, we made great progress with SRP 900, as the evidence base for this highly differentiated and potentially transformative therapy.
<unk> to Bill's earlier this year, we announced the expression results from the first 11 patients in cohort one of the Endeavour study 103, our first trial evaluating our commercially representative SRP 9001 material.
Across all measures that's genome copies per nucleus western blot expression protein positive fibers and intensity. We saw results that were as good or better than our previous experience with our clinical supply and materials.
We have by now dose sub 77, Duchenne children with our therapy across three studies and roughly three weeks ago. We provided a further update on the clinical evidence generated to date.
And our proof of concept study 101 at three years Duchenne patients continued to perform markedly better than the natural history of this aggressively to generating disease would predict achieving a nine point improvement on the 34 point Northstar ambulatory assessment scale or NSA.
And that's against natural history, with a P value of less than zero point.
Zero Zero Zero Award.
In a blinded placebo controlled study 102 part one we had previously reported that in the baseline matched four to five year old cohort.
At 48 weeks with treated children perform statistically significantly and clinically meaningfully meaningfully better than placebo at a P value of zero.
017 for the 6% to seven year olds, we recently reported that when properly baseline than age matched against the natural history cohort.
Treated six to seven year olds performed three points better than natural history with a statistical significance of 0.0129.
And finally, but importantly, we reported that in our endeavor study at only six months. The first 11 patients in cohort one have already improved against their own baselines by about three points with natural history would have predicted a 6% decline.
NSA over that same period of time.
After an enormous amount of work in progress CMC manufacturing research development and regulatory interaction.
CA cleared us to commence our pivotal trial for SRP 9001, known as embark.
As the first gene therapy pivotal trial for Duchenne in the United States.
In early October we announced the initiation of embark.
And on October 11 at our SRP nine here of zero, one micro district at R&D day, we provided more details on the design and key elements of the embark study.
He is actively recruiting.
We'll enroll a 120 patients at dozens of sites in the United States Europe and Asia.
Looking forward in addition to focusing on rapidly enrolling embark we will present the results from part two of study one or two for SRP 9001 in the first quarter of 2022 study one or two will provide additional insight as we execute embark which is our pivotal trial.
Beyond SRP 9001, we have seen consistently strong expression safety and functional signals from our proof of concept study for SRP 9003, or gene therapy to treat limb girdle muscular dystrophy type <unk>. We reported earlier this year that both U S and European regulators have suggested that they use.
Our beta circled why can't protein expression.
<unk> sufficient for accelerated and conditional approvals respectively.
In addition to advancing this dialogue with the agency in designing an appropriate pivotal trial are significant rate limiter is completion of the CMC work for commercially representative SRP 9003 material, we intend to complete this work next year.
With our strengthened balance sheet, we intend to move our sixth program <unk> portfolio forward and are exploring the potential for our platform approach to assignment simultaneously address our three <unk> programs <unk> and <unk> types do we.
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Now moving to our RNA franchise earlier this year, we announced positive results from.
Part a of our momentum trial studying our next generation peptide conjugated PMO PMO SRP 50, 51 that is designed to be an enhanced version of our PMO technology for Duchenne patients who are amenable to exon 51 skipping.
In the 30 Meg per kg cohort compared to a 10% we saw 18 times greater exon skipping an eightfold either level of dystrophin production and we saw this in half the time and at 20% of the drug exposure of a tap lesson.
We also saw dose dependent hypomagnesaemia, but believe that it is both monitor and manageable with prophylactic magnesium supplements.
We then gained FDA concurrence on the commencement of part B of momentum, which will serve as a pivotal trial for SRP 5051.
If confirmed at upcoming trials, our next generation <unk> mouse will greatly extend the reach and impact of our RNA platform platform with the potential to treat as many as 80% of individuals with Duchenne and opening up.
Opportunities outside of the United States with our bolstered balance sheet, we intend to advance multiple additional PMO therapies for other duchenne mutations.
In addition to these prioritized late stage programs, we have the balance sheet and expertise to continue to advance our broader 40, plus program research and development pipeline, including therapies for additional neuromuscular neurological and cardiomyopathy diseases, our work in new and improved.
Delivery mechanisms and advanced AAV capsid, and our work to improve gene therapy to permit dosing in the presence of preexisting antibodies.
And to empower re dosing.
At the same time, we continue to further strengthen our first in class team of genetic medicine professionals across technical operations Research development regulatory strategy just to name a few.
To that end in early October we celebrated the Grand opening of our World Class 85000 square foot genetic therapy center of excellence in Columbus, Ohio, and we continue also to build our gene editing innovation Center in Durham, North Carolina, which is focused on the advancement of CRISPR Cas nine.
We have made exceptional progress in 2020, advancing our large multi platform pipeline and sharpening our vision to be the leader in genetic medicine for the treatment of rare neuromuscular diseases and beyond I would like to thank our partners, our clinical investigators and the families participating in our trials.
For their commitment and important role in our recent success.
And I would also like to thank my exceptional team of professionals at <unk>.
Team that embraces with dedication our mission of using cutting edge science to improve the lives of those living with rare disease. Your tireless work and focus on execution shows and our advancements this year and I am confident that it will translate into a better life for the many patients who depend on our work.
And with that let me turn the call over to Ian <unk>, who will provide an update on the financials.
Thanks, Doug.
Afternoon all.
This afternoon and the financial results press release provided details for the third quarter of 2021 on a non-GAAP basis as well as the GAAP basis.
Please refer to release available on <unk> website.
Full reconciliation of GAAP to non-GAAP financial results.
We are quite we announced that for the third three months ended September 32021. The company recorded total revenues of $189 4 million compared to total revenues of $143 9 million.
For the same period of 2020, an increase of $45 $5 million.
Total net product revenue for the quarter of 2021 from our PMO exon skipping franchise was $166 9 million.
Compared to a $121 4 million for the same period of 2020.
The third quarter of 2021 individual net product sales were $115 $6 million for a 50 $126 $7 million for exon 45 and.
$24 $7 million for <unk> 53.
The increase primarily reflects higher demand for our products and the launch of a modest 45 and as Doug said due to continued strong performance. We further increased our full year 2021 revenue guidance range.
RNA franchise by $40 million.
In the quarter ended September 32021, and for the same period in 2020, we recognized $22 $5 million of collaboration revenue, which primarily relates to our collaboration arrangement with Roche.
Reimbursement co development costs under the Roche agreement totaled $29 $4 million.
Third quarter of 2021, compared with $16 9 million for the same period of 2020.
On a GAAP basis, we reported a net loss of $48 $1 million.
$196 5 million or 60, and $2 50 per basic and diluted share for the third quarter of 2021 and 2020, respectively.
We reported a non non-GAAP net loss of $15 $6 million or <unk> 19 per basic and diluted share in the third quarter of 2021 compared to a non-GAAP net loss of $111 5 million or $1 42 per basic and diluted share in the third quarter 2020.
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In the third quarter 2021, we've recorded approximately $23 $4 million and cost of sales compared to $15 million in the same period of 2020. The increase in cost of sales is primarily due to increasing demand for our products.
On a GAAP basis, we recorded $139 1 million and $194 million in R&D expenses.
Third quarter of 2021, and 2020, respectively, a year over year decrease 50 $51 $3 million.
Decrease is primarily due to a decrease in manufacturing and milestone expenses.
A decrease in manufacturing expenses related to the timing of our gene therapy batches and we expect these expenses to return to recent historical level now on a non-GAAP basis R&D expenses were 101 hundred $15 $1 million for the third quarter of 2021 compared to 159.
$9 million for the same period 2020, a decrease of $44 8 million.
Now turning to SG&A on a GAAP basis, we recorded approximately $61 $1 million and $75 $4 million of expenses for the third quarter to 2021 and 2020, respectively.
Increase of $14 $3 million a year over year decrease was driven primarily by a decrease in professional services personnel and compensation expenses.
On a non-GAAP basis, SG&A expenses were $43 6 million for the third quarter of 2021 compared to $57 2 million for the same period of 2020, a decrease of $13 $6 million.
On a GAAP basis, we recorded $26 million in other expenses net for the third quarter of 2001 compared to $14 $3 million in other expenses net for the same period of 2020. The increase primarily reflects an increase in interest expense incurred from our.
Term loan debt facilities due to an increase in the outstanding balance as well as an impairment loss related to our strategic investment partially offset by a reduction in interest expense incurred on our convertible debt related to the adoption of ASU 2000 Twenty's nationalistic.
We had approximately $1 $6 billion in cash cash equivalents and investments as of September 32021. Furthermore, in October we bolstered our cash position by approximately $550 million as a result of the net proceeds we receive from our equity offering and with.
That I will turn the call over to Darren for an update on our commercial activities talent.
Thank you Ian and good afternoon, everyone. The third quarter of 2021 saw continued revenue growth in all three of our PMO based exon skipping medicine.
As mentioned total net product revenue reached approximately $167 million, representing our second straight quarter with double digit growth versus the previous quarter.
And we approached nearly 40% growth versus Q3 2020.
The growth is being fueled by the strong launch for a modest 45, which has accelerated even further over the third quarter and is exceeding all our expectations around launch uptake.
Due to this continued over performance as Doug mentioned, the new guidance is $605 million to $615 million.
We are pleased to see our 2021 net product revenues increased by more than $150 million.
I will now outline individual net product revenues for our three approved PMO medicines I'll start with exon 51.
Revenue for example is 51 totaled over $150 million in Q3, 2021, representing a roughly 3% increase over the prior quarter.
This modest growth represent primarily incident patients and we expect Exxon is 51 revenue to continue at a similar trajectory in the coming quarters.
Moving on to buy <unk> 53.
Revenue totaled nearly $25 million in the third quarter, representing nearly 10% growth versus the second quarter of 2021.
This reinforces our leading position in the exon 53, and medical market, our expertise in Duchenne and the flawless execution of our team.
As mentioned last quarter the growth rate for <unk> 53 will predictably decreased as we work through the remaining start forms from the launch phase and approach the mature phase as with Exxon to 51, where growth will be driven primarily by incident patients.
The vast majority of exon 53 treated patients.
To be on by <unk> 53, even with the competitive launch.
Now moving on to a modest 45, where the growth is tracking ahead of the exon 51 launch trajectory.
Adjusting for relative population sizes the rate of new patient start forms for a modest 45 is in line with what we saw for example, <unk> 51 launch however, what's primarily driving the rapid growth for a modest 45 has been the decrease time to getting patients access to end on.
Therapy.
That time has been faster for a modest 45 than what we saw for exon 51 as a result, the team has delivered nearly $27 million in revenue in Q3 2021 with a modest 45.
The successful launch of a modest 45 is our third since 2016 and represents the dedication of our team who work every day on behalf of patients.
Our deep experience with Duchenne enabled us to serve more patients expedite access to drug and offer best in class support services through <unk> assist.
Our initial forecast models and the published epidemiology had suggested that the exon 45, and 53 amenable population.
Similarly sized however, given the strength of demand is 45 revenue uptake.
And the fact that this has now surpassed that of 553, we believe the exon 45, skip amenable patient population may be larger than the 53 skip amenable population and we'll continue to assess over time.
I'm extremely proud of the flawless execution of our team and.
And we will continue to apply learnings toward our number one priority.
Nearly 30% of individuals living with Duchenne, who may benefit from our PMO based.
Exon skipping therapies.
Now that we've demonstrated what we can do with our first three launches we stand ready to support the Duchenne community as we rapidly advance both our gene therapy pipeline.
We have built best in class U S field and case management team is focused on supporting patient access to therapy for appropriate patients.
As such we are ready to adapt to and execute on.
Any potential scenario that comes our way in the coming months and years.
Dallon: Now I'll turn the call over to Gilmore for an update on our research and development activities. Gilmore
Now I will turn the call over to Gil for an update on our research and development activities.
Bill Maher.
Gilmore: Thank you, Dallon and good afternoon, everyone. Over the course of 2021, including up to and through the third quarter, our R&D group has successfully delivered on its goal to support and advance Surreptus's leading position in RNA and gene therapy, both the strategy we set forth and the investments that we have made over these past two years to build and nurture our science and talent, and to leverage our expertise, have used as numerous and notable achievements, begin with the impressive progress we've made in advancing our gene therapy program.
Thank you.
Good afternoon, everyone over the course of 2021, including up to and through the third quarter. Our R&D group has successfully delivered on its goal to support and advance disruptive leading position in RNA and gene therapy.
Both the strategy, we set forth and the <unk>.
We have made over these past two years to build and nurture our science in towers and to leverage our expertise abuse as numerous and notable achievements I'll begin with the impressive progress we've made in advancing our gene therapy programs.
Gilmore: At the World Muscle Society Virtual Congress in September, we presented new data evaluating total binding antibodies against RAAV, RH74, or R874 in individuals with Duchen and demonstrated that a majority of those screened (84.8%) were seronegative at a cutoff of 100,000 tighter for anti-RH 74 total binding antibodies. And DUS would be eligible for gene transfer therapy with an R874 best. Now it's important to remember that the WMS presented data were derived from an interim analysis; a more recent analysis of the complete patient quarter demonstrated that 86. Were seren negative in these Duchenne patients, with a tighter cover of 1, and that is 13. 13.9% were negative.
At the World Muscle Society Virtual Congress in September we presented new data.
<unk> total binding antibodies again.
AAV <unk> 74, or <unk> 74 in individuals with Duchenne and demonstration that a majority of the screen 84, 9%. We're seronegative at a cutoff of 100 400 tighter for Anil.
Alright, 74 total binding antibodies.
<unk> would be eligible for gene transfer therapy with an RT 74 Becker.
Now it's important to remember that the WNS presented data were derived from an interim data cut.
More recent analysis of the complete patient cohort demonstrated 86, 1%.
<unk>.
These two sham patients.
With the type of cut off of $1 400, and that is 13, 9% we're seronegative.
Gilmore: Notably, the data also showed that seropreve did not increase with age in Duchenne patients age 4 to 18. This latter observation is very important for older individuals with more advanced disease considering therapy. These results, by the way, are also generally consistent with our own screening experience in our clinical interventional trial. Also, at World Muscle, we presented our three-year safety and functional outcomes data from study SRP 901- Specifically, functional assessments measured by NSAA showed overall improvements in motor abilities compared to baseline, and those improvements were maintained over three years, supporting a durable response and highlighting that the magnitude of benefits increases over time.
Notably the data also showed that zero prevalence.
Increase with age and Duchenne patients age four to 18.
This latter observation is very important for older individuals with more advanced disease considering therapy.
These results by the way also generally consistent with our own screening experienced in our chemicals.
Intervention product.
Also at World muscle, we presented our three year safety and functional outcomes data from study SRP nine years or one 101.
Specifically functional assessments measured by NSA showed overall improvements in motor ability compared to baseline and those improvements where it maintained over three years.
Coursing, a durable response and highlighting that the magnitude of benefit increases overtime.
Gilmore: The data also shows that SRP 9101 is well tolerated with no new safety signals, consistent with safety data from the wider SRP 9001 chemical program. Most recently, and as Doug mentioned, we presented a roll-up of data across the SRP 901, 102, Part 1, and 103 studies at our October 11th Microdestrophan Day. As reported, we possess a wealth of data across 77 Duchenne patients dosed with SRP 901 45 of these patients have been dosed with clinical process material, and 32 have been dosed with commercially represented material.
The data also show that SRP, 9001, and well tolerated with no new safety signals consistent with safety data from the wider SRP nine years or one clinical program.
Most recently and as Doug mentioned, we presented the roll up of data across the SRP nine years or one 101 102 part one and 103 study.
October 11th micro dystrophin data.
As reported we possess a wealth of data across 70, Duchenne patients dosed with SRP nine years or in three ongoing studies.
45 of these patients have been dosed with critical process materials and 32 have been dosed with commercially represents a material.
59.
Gilmore: 59 of the 77 were ambulatory boys aged 4 to 8 at the time of dose; 12 boys were older than eight years of age at the time of dose, and of those 12, six were non-ambulatory. In summary, we have experienced a broad population that includes a wide age range of 4 to 19 euros and a very wide weight range between 13.7 to 80.1 kilograms.
77, where ambulatory boys, aged four to eight at the time of dosing.
Boys were older than eight years of age at the time of dosing and of those 12, six where non ambulatory.
In summary, we have experienced a broad population.
A wide age range of 4% to 19 road and a very wide weight range between $13 seven to 81 kilograms.
Gilmore: In this broad patient population, we are encouraged to have observed a consistent safety profile with the most common AE being vomited. The increases observed in liver enzymes that we have responded favorably to transient increases in cortical steward, and we have not observed clinically relevant counterfeit activation or thrombotic microangiopor. As Doug noted, we are thrilled to be initiating in Borg or study 301, the first global registration trial of gene therapy for the treatment of Duchain.
In this broad patient population, we are encouraged to absorb observed a consistent safety profile with the most common eight using balance sheet.
The increase was observed in different zones that we haven't have responded favorably to transit increases in cortical steroids, and we have not observed clinically relevant comfort activation or thrombotic microangiopathy.
As Doug noted we are thrilled to be initiating embark for study 301, the first global registration trial of the gene therapy for the treatment of Duchenne.
Gilmore: The study will use our commercially representative SRP 901001 material. Embark has been designed as a double-blind, randomized placebo-stable control study and is powered to confirm that our SRP 901 microdistrophin commercially representative materials at a dose of 1.3 to the 14, using a linearized, captic standard for titoac, confers chemical functional benefits in 4 to 7-year-old boys. The study will enroll 120 patients with randomization using two strata, age with So age and NFAA at baseline are the stratas.
The study will use our commercially represents with SRP nine years or one material.
Gilmore: Building on the learning study 1 or 2 part 1, we are including patients with a time to rise from the floor or from supine of less than five seconds. Patients have been randomized, and we expect to fully involve them in the study in the first half of 22. Now, moving to our Lim-Girdle portfolio, S-RP-N-03 is our lead Lim-Girdle program with which a full-end stalker glycan CD&A uses the same AV-GER, RH74's HFET, and MHCK7 promoter as the SRP 901 program and has generated exciting expression and functional data in the ongoing SRP 903 101 study.
311 study.
We are currently in dialogue with old half of the FDA about the suitability of our commercial representative SRP 90 days or three materials to start Registrational 34 S. A P 93.
Gilmore: We are currently in dialogue with OTAT at the FDA about the suitability of our commercially representative SOP 9003 materials to start a registration study for SOP 9003. We are using the learning from the SRP 901 program to advance SRP 9003 and the entire sarco-glycan pork furlough in addition to our disferlans, calpane, and other non-sarclican programs. In passing, we attended the cellular tissue and gene therapy advisory committee meeting to discuss the toxicity risks of asno-associated virus vector-based gene therapy. Our key takeaway was that our RH74-74 PAPS maintained a differentiated safety profile.
We are using the learning from the <unk> from one program to advance <unk> and the entire start with like in Portugal. In addition to our does further calpain and other non talked with like a program.
Impacting we attended descending or tissue and gene therapies Advisory Committee meeting to discuss the toxicity risks.
The associated buyer Vectra base gene currently are key takeaway was that are already 70 forecasted maintains a different agents safety profile.
Gilmore: That's consistent and manageable using a single drug steroid immunosuppressive regime. Additionally, I'm pleased to report that our Lim-Girdle 501 Natural History Study is active and enrolling. This study represents our commitment to understanding the complexities of this rare group of diseases. Now let me turn to the important advances from our proprietary RNA platform. I was struck with our next generation peptide conjugated phosphoryamidate morphilino oligermark, or PPMO, S.R.P.151, which demonstrated unprecedented clinical results in individuals with Duchenne who are amenable to Exxon 51 skipping, were reported in early May 21 positive clinical data from the 30-pric arm in Part A of the mental study, which evaluated safety and change from baseline at week 12 for exon skipping and dychrophen expression in both ambulatory and non-ambitory, The data shows that the 30-k-kate cohort, dose once monthly, when compared to the current standard of care at Teperson, demonstrated an 18-fold increase in ex-ounce skipping, and more than 6.5% mean to stroke and poaching expression as measured by Western bloc. These results were not driven by a single patient.
That's consistent and manageable using a single drug steroids Immunosuppressant version.
Additionally, on Pete report that are limb girdle fiber one natural history 30 is active and enrolling.
This study represents our commitment to understanding the complexities of this rare group of diseases.
Now, let me turn to the important advances from our proprietary RNA platform I was stronger than our next generation peptide conjugated Phosphorothioate date, morpholine oligarch or P. PMO, SRP, 50, 51, which demonstration unprecedented clinical results and individuals with Duchenne, who are amenable to Exxon 51 skipping.
We reported in early May 21 positive clinical data from the 30 make petite arm and part of the mentioned study, which evaluation safety and change from baseline at 12 for Exxon skipping a description expression in both ambulatory pants non ambulatory patient.
Data showed that the Turkey make petite Colbert dose once monthly when compared to the current standard of care. A 10 person demonstrated an 18 fold increase in economics, skipping and mortgage six 5%, meaning to spoke with coaching expression as measured by western blocked.
These results were not driven by a single patient older patients responded well to therapy and based on a predictive model, we should achieve greater than 10% destroy with one sprint dosing overtime.
Gilmore: All the patients responded well to therapy, and based on our predictive model, we should achieve greater than 10% dystrophin with one sperm dose. However, over time, we observe that baseline dystrofen levels are not a predictor of post-treatment discussion. In fact, we observed that two patients with the lowest baseline had the highest level of post-treatment Importantly, SRP 5051 demonstration has a tolerable safety profile, We continue to believe the hypersinine observable study remains manageable and manageable with magnesium supplementation and is not correlated with changes in renal function.
Further.
We observed that based scientists frozen levels are not a predictor up for treatment of depression.
In fact, we observed the two patients with the lowest baseline how the highest level of posttreatment expression.
Importantly, SRP 50, 51 demonstration Todd to safety profile.
We continue to believe the heightened magazine observe the study remains monitor and manageable magnesium supplementation and is not correlation with changes in renal function.
Gilmore: Importantly, we are currently initiating part B of the mental study, which we anticipate will serve as our pivotal trial for SRP 5051. To remind you, at the end of September, we announced the trial design. Studies will enroll between 20 to 40 patients amenable to Exxon 51 skipping who are naive to SRP 5051 and are between the ages of 7 to 2028. Both ambulatory and non-ambulatory patients are eligible for participation, along with previously treated, a treatment- Approximation 30 additional patients previously treated with F5051 will be eligible to participation partners.
Importantly, we are currently invitation Parthia from Amendment study, which we anticipate will serve as our pivotal trials for SRP 50 51.
To remind you at the end of September we announced the trial design.
Equal enrolled between 20 to 40 patients amenable to Exxon 51, skipping who are naive to SRP 50, 51 and are between the ages of 17 to 21.
With ambulatory amount ambulatory patients are eligible for participation along with priest to be treated.
And AAA patient.
Approximately 30 additional oppression previously cigarettes would be 50, 51 will be eligible to participate in party.
Gilmore: As we initiate part B, we remain very excited by the SRP 5051 clinical results and the potential the therapy holds to offer patients with Duchenne a more convenient once-per-month treatment option with a meaningful safety profile and superior dystrophic expression. Now we'll be to update our PMO program.
As we initiated heartbeat, we remain very excited by the SRP 50, 51 cynical results and the potential of the therapy holds to offer patients with duchenne and more convenience lump promote frequent options with a medical safety profile and superior destruction, especially.
Now moving to update for our PMO program enrollment.
Gilmore: Enrollment, for essence, for Tasmersen and Golodderson and admission for study for 10% continues. We maintain regular contact with the FDA to update them on our progress toward delivery of these important chemical data. In September, we also presented two new sets of support of chemicalization for Tasmress and the Teperson. First, with an interim biopsy analysis from essence of Kazamerset treated patients, demonstrating that Xx4-F skipping assessed by a digital drop PCR would significantly increase in all Kazamersin Treated patients compared to baseline, with a P value of less than.001.
Enrollment for instance for <unk> and ambition.
Study for a temper some continue we.
We maintain regular contact with the FDA to update on our progress towards deliberately important clinical data.
In September we also presents a two you said supported clinical days for customers and the type of person that word method.
But first with an interim biopsy analysis from essence, a chasm recipes patients demonstrated that excellent 45, skipping a test by additional drop TCR significantly increased and all counselors increased patients compared with based on the P value of less than 0.001.
Gilmore: Receiver-treated patients did not demonstrate an increase in P, 0 means dystrophen levels by western blot significantly increased from Bayside after 48 weeks of Kazamercing Treatment with a p of less than.001, with a significantly greater increase in the strofen levels compared to placebo, a p of 0.004, and increased the strofen positively correlated with exxon skipping, the experiment ranked correlation Kazamersen was well tolerated with most adverse events, cathitis mild and unrelated to Kazamersen, with no suggestion of kidney toxicity.
Casino treat patients did not demonstrated increase P 0.8.
Mean, just wrote tremendous direction blossom significantly increase for baseline after 48 weeks of customers with a P at left and put their agenda.
One with a significantly greater increase in stroke levels compared to placebo.
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Increase the trophy partners Mccarley with excellent skipping.
Hiraman ranked correlation of 0.627 P. M S N.
Those are the ones.
Chasm Russell was well tolerated with most adverse events.
Model and unleashed customers with no suggestion of kidney toxicity.
Gilmore: The second was a presentation of study 4658102, the first clinical trial in patients with Duchenne aged 6 to 428 months. The oldest population being evaluated in clinical trials today. This trial demonstrated that Teperson, IV 30 weeks per kid once weekly, was well tolerated, with no new safety signals after 96 weeks of treatment and no discernible difference between age courts divided as six to less than 24 months versus 24 to 48 months.
Second with the presentation of study 46, 58, one O two the first clinical trials in patients with Duchenne, aged six to four th month.
The oldest population duchenne evaluations and the clinical trials to date.
This trial demonstrates that a tech person Ivy pretty big cake once weekly with well tolerated with no new safety signal. After 96 weeks of treatment and no discernible difference between H court divided six to less than 24 months versus 24 to 48 months.
Gilmore: These data are consistent with what's been seen following treatment of Teperson in older patients and provide valuable data for families and prescribers. In closing, and very importantly, I want to thank all of the patients, their families, and the study investigators and coordinators who have done so much in contributing to our study designs in addition to participating in our many clinical trials. I also thank my R&D colleagues and our partners who have done so much work under prolonged, difficult circumstances caused by the pandemic to maintain our urgent mission to deliver new, highly effective therapies to people where they are needed. I will now turn the call over to Doug to open the Q&A session.
This ain't or consistent for Washington, furnishing, the tempers, an older patient and provide valuable data profoundly prescribed it.
In closing very importantly, I want to thank all of the patients their families in the study investigators and coordinators hooked on so much and contributing to our study designs. In addition to participating in our many clinical trials I also think my R&D colleagues and our partners hooked on so much for our country prolonged difficult circumstances caused by the pandemic.
To maintain our urgent mission to deliver new highly effective therapies to people who work.
I will now turn the Colo too dark to open the Q&A session Doug.
Dr. O'Neill: Thank you very much, Dr. O'Neill. Chino, let's open the call for questions.
Thank you very much Dr germ El Chino much open the call for questions now.
Chino: All right, so as a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Again, that is star 1 on your telephone.
Alright, so as a reminder to ask a question you will need to press star one on your telephone to resolve your question press. The pound key again that is star one on your telephone please theme it yourself to only one question.
Chino: Please limit yourself to only one question. The first question comes from the line of Tazin Ahmad from Bank of America. Your line is now open.
First question comes from the line of <unk> from Bank of America. The line is now open.
Tazeen Ahmad: Hi, good afternoon. Thanks for taking my question. Doug, as far as bark goes, can you just remind us again what the use of steroids is going to be in the study and how it's different from what you've allowed in study 102?
Hi, good afternoon, Thanks for taking my question.
As far as embarks task can you just remind us again when did you sense.
Steroids is going to be in this tiny and how it's different from what you've Aladdin anyone in half.
Doug: It will be the same. It will be the same.
It will be the same it will be the same so.
Tazeen Ahmad: And can you tell us how doctors used steroids in 1022?
And can you tell us how that enhanced enright and when is it.
Yeah.
Dr. O'Neill: Dr. O'all, do you want to address that?
Dr Germ, you'll do you want to.
Address that.
Dr. O'Neill: Yes, so we use prednisone; many of the patients are actually, indeed, are already on a patient as a standard of care, on prednisone as a standard of care. We require that they run in on prednisone to avoid any adverse impact or spurious impact on signal. The way that the patients are dosed on prednisone is that we, just to simplify it, double the standing steward regime they're on. And they, uh, they, they, start that at doubling at the time of infusion and maintain that regime, and they are tapered after 60 days.
Yeah.
So we use a prejudice at many of the patients are indeed are already on patient of the standard of care unprecedented standard care.
We require that they run in on prednisone to avoid any adverse impact our spirits impact on signal the way that the patients are dose on prednisone is that we just to statistically pushes doubled.
The standing stirred regime, there on and they.
Start dash at Dublin at the time of infusion and maintain that regime and our papers after 60 days.
In the event of any.
Dr. O'Neill: In the event of any liver enzyme change, we titrate that prednisone up, but our experience to date has been very positive in that those liver enzyme changes respond to the transient elevation of prednisone, and they've returned. Then, after 60 days or after that initial up titration to their baseline maintenance therapy, which is partially the standard of care for Duchenne.
Liver enzyme change.
Typeface that prednisone up.
But our experienced todays has been very positive in that those liver enzyme changes respond.
To the transience elevation of prednisone and they'd returned then after 60 days or after that.
Initial titration to their baseline maintenance therapy, which is part of the standard careful duchenne.
Anupam Rama: All right. The next one on the cue is Anupum Rama from J. Morgan. Your line is open.
Alright next one on the queue is I knew from Rama from J P. Morgan relies on open.
Anupam Rama: Hey, thanks so much for taking the question. Just a really quick one from me.
Hey, guys. Thanks, so much for taking the question just a really quick one for me.
Doug: For the Part 2, Study 102 results, the guidance is for 1Q data. So should we be thinking about in and around sort of an in-person healthcare conference in January in San Francisco, or is this later in the quarter? Thanks, so much.
Park to study one O. Two results. The guidance is 412 data so should we be thinking about in and around sort of Ah.
In person healthcare conference in January in San Francisco or does it later in the corner. Thanks, so much.
No problem I can't think of any any conference is happening early in the year.
Doug: You know, I can't think of any conference that is happening early in the year. I can't commit to the exact day. Obviously, I'm joking, Anapom.
I I can't commit to the exact Gail obviously joking.
Brian Corey Abrahams: I can't commit to the exact date. We have to get all the data in QC, and it will be in the first quarter. It will be in the earlier part of the first quarter. But I can promise that as soon as we have it in and fully QC'd, then it's ready to present, we'll do that. And if it's early enough for, for, a particular event, we will consider that. But we can't make that commitment yet because we just don't know how long it'll take to get the data in from QC.
No problem I can't commit to the exact date, we have to get all the data in in QC. It will be in the first quarter and it will be in the earlier part of the first quarter.
But I.
Promise that as soon as we have it.
And fully QC, then it's ready to present will do that and if it's if it's early enough for four.
A particular event, we'll consider that but we can't make that commitment yet could you just don't know how long will take to get the data and and to see it.
Brian Corey Abrahams: For the next question, we have Brian Abrahams from RBC Capital Markets. Your line is now open.
For the next question, we do have Brian Ramstrom RBC capital markets. Your line is now open.
Brian Corey Abrahams: Hi, good afternoon. Thanks for taking my question and congrats on all the progress. A question on the Limgirdle program; I'm curious about your latest views on how you're envisioning a potential trial if indeed expressions sufficient for approval. Might this be a 12-week study with longer follow-up as a confirmatory study? Would you look at 2E or all the different subtypes, placebo-controlled versus open label? And then, along those lines, I'm curious sort of how far along you guys are.
Hi, Good afternoon. Thanks for taking my question and congrats on all the progress a question on the limb girdle program I'm curious your latest views on how you envisioning a potential trial, if indeed expressions sufficient for approval might just be 12 week study with longer a follow up and just confirmatory study would you use look at <unk>.
We are all.
All the different subtypes placebo controls versus open label and then along those lines I'm curious sort of how far along you guys are with respect to the manufacturing process an assay development.
Brian Corey Abrahams: With respect to the manufacturing process and assay development for Limgirdle, is this something where you'd need to complete that process and any bridging work before you meet with regulators, or might you meet with regulators to start to contemplate a pivotal trial design in parallel? Thanks.
Four.
Limb girdle is this something where you'd need to complete that process and any bridging work before you meet with regulators or might you meet with with regulators to start to contemplate a pivotal trial design in parallel thanks.
Doug: Okay, great. Let me answer the second question first. So we've made a lot of progress, as you can imagine, with respect to process development and analytical development for our commercially representative process for 9003, and we've been well informed by all of the work that we've done for 9001 and informed by all of the conversations that we've had with the FDA, so we have good guidance on that. But work remains. I want to be very clear about that, particularly in the analytical.
Okay, Great. Let me answer the second question first so we've made a lot of progress as you can imagine with respect to process development and analytical development for our commercial representative process for 9003, and we've done well informed by all of the work that we've done for 9001 and then informed.
By all of the conversations that we've had with the FDA and so we are good guidance on there, but but work remains so I'm going to be very clear about that.
Particularly on the analytical side of things a significant amount of work still remains so this will occur in 2022, but the team is doing a brilliant job of continuing to progress. This on this study design and let me and I'll say one final thing about the second part which is we can we can and we already have simultaneously in the.
Doug: on the side of things, a significant amount of work still remains. So this will occur in 2022, but the team's doing a brilliant job of continuing to progress this. On the study design, and let me, and I'll say one final thing about the second part, which is, you know, we can, we can, we can, and we already have simultaneously engaged with the agency about clinical design while we're working on the process development, and analytical development, and GMP release for the material. And that's why we have some initial.
<unk> with the agency about clinical design, while we're working on the process development and analytical development GMP release, where the material and that's why we have some initial signals from both the us and X USA agencies that.
Doug: from both the U.S. and ex-US agencies that the potential for an accelerated or conditional approval is possible. I do think that the most productive next meeting will be a meeting when we can have a discussion at the same time; this is what we did with 9-001. We can have one very thoughtful discussion about both the clinical design and the appropriate clinical design and show the agency where we are from a CMC perspective and get them comfortable both with the technical operation side as well as the development side. Because it is clear, as we have all seen, it's very clear that being very buttoned down on the CMC side is extraordinarily important.
The potential for an accelerated or conditional approval as possible I do think that the most productive next meeting will be a meeting where we can have a discussion at the same time. This is what we did with Nigeria zero. One we have one very thoughtful discussion about both the clinical design the appropriate clinical design and show.
The agency, where we are from a CMC perspective.
Get them comfortable both about the operation side as well as the development side because it is clear as we have all seen it's very clear that that being very button down on the <unk> site is extraordinarily important. So we'll work on those discussions and eventually have to get both of those done before we commence our next trial on the.
Doug: So we'll work on those discussions and eventually have to get both of those done before we commence our next trial. On the clinical design itself, we've got more work to do, and the teams are doing a lot of thinking around this issue. In the broadest of strokes, of course, what one knows is that if you're going to seek an accelerated approval, you would have two elements, whether it's one study that leads into an extension or whether it's two studies.
The clinical design itself, we've got more work to do and that seems like a lot of thinking around this issue in the broadest of strokes of course, what one knows is that if you're going to seek an accelerated approval you would have two elements, whether it's one study that leads into the extension or whether it's two studies you have to have an early.
Doug: You have to have an element that provides confidence that using a biomarker, in the case of TUE, which would obviously be the beta cycloglycan protein, you would have a protein that has that expression that's reasonably likely to predict the clinical benefit.
Or is that <unk>.
Provides confidence that using a biomarker in the case of chewy would obviously be the beta cycle like it cyclical I can't protein that you would have a protein that is that expression, that's reasonably likely to predict a clinical benefit and then you have a second part postapproval, where you confirm through additional work the functional benefits predicted.
Doug: and then you have a second part post approval where you confirm through additional work the functional benefits predicted by the biomarker. We've got more work to do and more thinking to do on that, because, as you may have seen or heard in my opening remarks, one of the things we're pondering, at least as we track into 2022, is if we want to start accelerating the other sarco glyccccc work as well and perhaps have an approach. That brings them together, perhaps, even into one basket study or close together so that they're actually tracking closer together.
The biomarker, we've got some more work to do and more thinking to do on that because as you may have seen or heard in my opening remarks, one of the things we're pondering at least as we.
As we track into 2022 is if we wanted to start accelerating the other circle oblique and that CMC work as well and perhaps have an approach that brings them together, perhaps even into one basket study or close together. So that they are actually tracking closer together. So short answer is we have a ton.
Doug: So the short answer is that we have a ton of work to do there. The good answer is that we have the resources to do all of that work. As you know, we previously had been saying we had about $1.6 billion of cash and cash equivalents on our balance sheet. We went and raised more money, you know, just about three weeks ago. We're sitting in a position right now where we have over $2 billion, significantly more than $2 billion in cash equivalent.
Kind of work to do their good answer is that we have the.
The resources to do all of that work as you know, we previously had been saying wait about $1.6 billion.
Cash and cash equivalents on our balance sheet, we went and raised more money.
Just about three weeks ago were sitting in a position right now we have over $2 billion significantly over $2 billion in cash or cash equivalents and we have really robust sales and you seem really good sales growth and that will continue into 2022, and so we have the resources to.
Doug: And we have really robust sales, and we've seen really good sales growth, and that will continue in 2020. And so we have the resources to bring all of these programs along. I mean, one of the things, you know, this hasn't been asked yet, but I'll answer it.
To bring all of these programs along I mean, one of the things of this this hasn't been answered asked yet, but I'll answer one of the things we really wanted to insurers that we had the resources not only to execute a lot of our late stage programs to make sure that we are accelerating the lib girdles were getting all of those Liberals moving as fast as possible given we see them as an extraordinary opportunity to do.
Doug: One of the things we really wanted to ensure was that we had the resources, not only to execute a lot of our late-stage programs, but also to make sure that we're accelerating the limb girdles, and we're getting all of those limb girdles moving as fast as possible, given what we see as an extraordinary opportunity to do good with a high probability of success and, together, a compelling commercial rationale. And over on the PPMO side, the same answer with the signals we've seen now on SRP 50-51.
Good with a high probability of success and together.
A compelling commercial and rationale and over on the P. BMO sides say an answer with the signals. We've seen now on SRP 50, 51, one of the things we really wanted to make sure. We can do is start getting the work done on other construct beyond SRP 50, 51, so that we get the broader ppm PMO.
Pipeline, moving as fast as possible and hopefully hopefully in the patients as soon as possible.
Alright excellent on a Q is solving rich.
Doug: One of the things we really wanted to make sure we could start getting the work done on other constructs beyond SRP 5051 so that we get the broader PPMO pipeline moving as fast as possible and hopefully in patients as soon as possible.
Which they're from Goldman Sachs. Your line is open.
Afternoon. Thanks for taking my question Escuela <unk> steady weeding out in the beginning of the year. So that the two year data and the crossover data here and could you just comment on whether there is any changes being implemented to park Q versus part one and also what.
Salveen Jaswal Richter: Right, next one on the cue is Salzance, uh Richster from Goldman Sachs. Your line is now open.
Given what you saw in part one how do you think about that translated into a positive outcome in part Kale.
Doug: Yeah, so there are a couple things to consider. The biggest difference between part one and part two, I would say, is in addition to the fact there are far more patients, of course, in part two, because all of the children now, all 41 of them will be on active therapy, we'll be looking at those children against a natural history cohort, right? There isn't a placebo arm to test against because all of the children in the crossover have now received the dose with therapy. So we have 41 children, some, half of them, two years worth of data, and the other half,
Yeah. So there's a couple of things to consider the biggest difference between part one and part two I would say is in addition to the fact there are far more patience of course in a sense in part too because all of the children now while 41 of them will be on.
Active therapy is that we'll be looking at those children against the natural history cohort right. There aren't there isn't a placebo arm to test against because all of the children and the crossover have now.
Then dose with therapy. So we have three one children some have about half of them.
Two years worth of data and the other half will be.
Gena Wang: The next question comes from the line of Agino Wong from Barclays. The line is now open.
One year's worth of data with a trajectory of the year leading into that we can look at all of that and look at it against the natural history cohort as well, let's see what is the site. We have so I guess there are two things that happen in part one that we're frustrated one of course was the issue of the target dose in in the first.
Gena Wang: Thank you for taking my questions. I have one regarding the Momentum Part B, PPMO program. Do you still need FDA confirmation on the pivotal study design? And I understand you have three cohorts. Can you give a little bit more color on the study design and the powering assumption?
Cohort of children about 60% of those children had lower than the target dose on the crossover with the new tiring method that we have employed this linear tiring method that does not exist. So all of the kids in the cross over and that have that got dosed on crossover.
Doug: Yeah, I'll broadly answer the first part, and I'll ask Dr. O'Neill to just describe, very, very briefly, the cohorts that are in Momentum Part B. I mean, the short answer is that we have the agency's blessing to proceed to Part B. Part B will be our pivotal trial. We'll be using the accelerated approval avenue. The good news with the Neurology Division and Dushen Musco Distrophy and District of Reduction is that we have very good precedent for that.
All of those children will have had the proper.
Dos the target intended dose 133, either the 14th and then the second thing is that using a natural history cohort we can.
Properly match them against not only their age but also their baseline characteristics. So.
What I will say is I think that part two will be very insightful as we execute embark on a pivotal trials for SRP 9001.
Next question comes from the line is a gene one from Barclays. So one is now open.
Doug: It's like there's guidance on disciplinopathies around this. So our pathway is pretty, pretty direct and certain, and the agency has blessed us to commence the momentum study, Part B. But with that, Dr. O'Neill, perhaps you can talk about the co-verts that are Part B. Thank you very much. So this is Part B.
Thank you for taking my questions asked one regarding momentum Pi B P. PMO program do you still need the confirmation on the pivotal study design.
I understand you have a three cohort can you give a little more color on study design an appalling assumption.
Yeah, I'll I'll broadly answered the first part in our last Doctor O'neill to just describe very very briefly the the cohorts that are in momentum Barbie I mean, the short answer is we have the agency's blessing to proceed to part B B will be are pivotal trial will be using the accelerated approval Uhm Avenue.
Dr. O'Neill: Thank you very much. There's actually one cohort, but it was comprised of two populations, SRP 5051 naive patients who would be newly written to the study, and we are allowing another 30 patients who have previously been exposed to reenter the study. There will be a run-in safety period, and then the patients will be randomized to one of two doses. And in answer to your final question, the study has been powered around dystrophin expression.
The good news with the neural Gnomology Division.
And Duchenne muscular dystrophy and distribution reduction is that we have very good precedent for that doesn't guidance on district monopolies around this so our pathways pretty pretty.
Direct uncertain and the agency has blessed us to commence the momentum study puppy, but with that Doctor and they'll perhaps you can talk about the gas.
Pardon me that works.
Thank you very much so did the party, there's actually one cohort, but it will comprise two population.
Alicia Young: Next one on the Q is Alicia Young from Cancer. The wine is open.
And 14.
60, 61 naive patients.
Doug: Hey guys, thanks for taking my question. I was just curious about momentum. I know since it's, you know, getting underway, and it's only really 20 to 40 people, if you have any kind of perspective on timelines, then would they be similar, maybe some of the other studies of similar sizes in the past, and then also, I mean, should we think about this as kind of lifecycle management at the Teflor Center, or how do we think about that? Thanks.
Who would be new York's the study and we are allowing the another 30 patients who have previously been exposed to re enter the study.
There will be a running at safety period, and then the patients will be.
Randomized to one or two doses.
I need to ask you to your final question. This study has been powered around distrustful expression.
Versus baseline.
Thank you very right.
Mhm next one on acute is Felicia young from cancer the lines open.
Hey, guys. Thanks for taking my question.
I was just curious.
Doug: So let's start with the first part. So, in dealing with enrollment, one must remember that momentum is different, for instance, than the 9-001 study in Bark and that it's a subset of children with emoscor dystrophy, and it's X-on-51, and there are other programs that we're competing with, so it will take a bit longer to enroll than you might imagine just given the total number. So it'll be the really second half of 2022 before it's school fully enrolled.
With momentum I know it since it's getting underway like and it's only really 20 to 40 people. If you have any kind of perspective timelines and where would they be similar and maybe some of the other studies have similar sizes of the past and then also I mean can we think about this is kind of lifecycle management on a.
Tupperware Center, how do we think about that thanks.
So let's start with the first part so.
First dealing with enrollment one must remember that.
Momentum is different for instance in the 9001 study embark in that it's a subset of children with muscular dystrophy in there and it's excellent if you want and there are other.
Programs that were competing with so it will it will take.
A bit longer to enroll that you might've actually just given the total number so it'll be.
Really second half of 2022 before it's fully enrolled and then.
Doug: And then, you know, I would say, I would look at it, the PPMO platform as a whole, SIP 5051 itself, and then the PPMO platform as a whole, as more than simply a line extension strategy. I think there is a real enormous potential, at least in the U.S., to have something that is significantly transformative both in the U.S. and outside of the U.S. As we know, given the approach that was taken to the approval of Exondis, our approvals in the United States, and there are very few places outside the United States where it's approved right now. We have a managed access program, so there is some access outside the United States, but the lion's share of the use of this therapy right now is in the United States.
I would say I would look at it the PMO platform is a whole FFT 50, 51 itself and then the PVM a platform as a whole.
As more than simply a line extension strategy I think there is a real.
Enormous potential at least.
To have something that is.
Significantly transformative boats in the U S and outside of the U S. As we know given the the approach that was taken to the approval of Exxon. This.
Our approvals in the United States and there are very few places outside the United States, where it's approved right now we have we haven't managed access program. So there are various some access outside the United States with them.
Lion's share of the use of the therapy right now is in the United States. The Peavey amount can do a number of things first of all if it is confirmed and the trials it'll be a transformative.
Doug: The PBMO can do a number of things. First of all, if it's confirmed in the trials, it'll be a transformative additional benefit to children who are already benefiting from our current PMOs. It bears repeating that in literally a shorter period of time, half the time, of a tepperson at 20% of the dose, we're seeing nearly an order of magnitude more district from production. The literature would suggest that could be completely transformative to children with Duchenne, and we can do this repeatedly.
Additional benefit to children, who are already benefiting from our current Pmo's has been.
Bears repeating that we're seeing in a <unk> literally a shorter period of time half the time of a 10% 20% of the dose we're seeing nearly an order of magnitude more district reproduction. The literature would suggest that could be.
Completely transformative to children would you Shannon we can do this repeatedly we can we can fairly directly do it for 50% of Duchenne and theoretically we can get that over 80% of do shed. So just the opportunity for the expansion is enormous amount of course X U S. I think the opportunity to get approvals X U S increases dramatically.
Doug: We can fairly directly do it for 50% of Duchenne, and theoretically, we can get to over 80% of Duchenne. So just the opportunity for the expansion is enormous. And then, of course, XUS, I think the opportunity to get approvals for XUS increases dramatically with this increase in the amount of dystrophin that we could make with the PPMO. And you can see what we can do with a therapy.
With this increase in the amount of dystrophin that we can make with the P. PMO and you can see what we can do with a therapy. We all we have now about 29% of Duchenne covered just in the United States for the most part just primarily in the United States with a scientist by on this and demand us and we've had our 20th.
Doug: We are, you know, we have, you know, we now have about 29% of Duchenne covered just in the United States, for the most part, primarily in the United States with Xandis, Vionis, and Amondis, and we've had our 20th quarter of sustained, strong growth. We've had a caggar from 2017 of 40%. If we hit the midpoint this year, it'll be over 40% CAGER. So the opportunity here to do good and do well for our investors with the PPMO, I think, cannot be.
Quarter of sustained strong growth, we've had a keg or from 2017 of 40% we hit the mid point this year it'll be over 40% Conger.
So the opportunity here to do good and do well for our investors when the P. GMO I think is cannot be.
Doug: I mean, it really is a significant opportunity for the Dushen community, both in the U.S. and XUS and also for those of us who, you know, those investors who have stayed with us and committed themselves to surrounding them.
<unk> that is really is a significant opportunity for the to shed and community. Both in the U S and X U S and also for.
Those of US who those investors who have stayed with us have committed themselves to surrender.
Matthew Harrison: The next question comes from the line of Matthew Harrison from Morgan Stanley. The line is now open.
Alright next question comes from the lineup Matthew Harrison from Morgan Stanley the lifestyle open.
Matthew Harrison: Great, thanks very much for taking the question. I was just wondering if you could comment a little bit in more detail on Momentum Part B as well, just around safety and, you know, the size of the safety database or the duration of the safety database that you might need there or any special considerations from an FDA perspective. Thanks.
Great. Thanks, very much for taking the question I was just wondering if you could comment a little bit in more detail for momentum part D as well just around.
Safety and the.
The size of the safety database or the duration of the safety database that you might need there any special considerations from an SDA perspective. Thanks.
So we'll have about 60 patients that's.
Doug: So we'll have about 60 patients, significantly more than we've had for the other PMOs. We should have a fairly significant number of patients, and of course, the agency has blessed this study in its size. And then from a safety monitoring perspective, the look from an expression perspective is 28 weeks. However, our working assumption is the agency would like to see longer follow-up than 28 weeks, so I would guide to one year for the safety follow-up as a basis for the accelerated approval. Table.
Significantly more than we've had for the other pmo's, we should have a fairly significant number of patients and of course. The agency has blessed this study and its size and then from a safety monitoring perspective.
The look from an expression perspective is 28 weeks are working assumption is the agency would like to see longer follow up within 28 weeks. So I would guide to.
One year for the safety follow up as a basis for the accelerated approval.
Gil Blum: The next question comes from the line of Gil Blom from Needham and Company. Your line is now open.
Next question comes from the line of Guildswoman from need him a company. So I so open.
Gil Blum: Good afternoon and also congratulations on a very strong quarter. Maybe a bit of a question on PMOs more broadly, we can reach around 80% of patients. But so far, in the PMO programs, you have to kind of approve each new targeted population by itself. Is there a basket approach here somewhere, maybe, kind of like what you're looking at at LGMB? Thank you.
Good afternoon, and also congratulations on on a very strong quarter.
Maybe a bit of a question on P. P M o's more broadly.
So.
We can reach around 80% of patients.
But so far the PMO programs, you have to kind of prove.
Each new targeted.
Population by itself is there a basket approach here somewhere maybe kind of like what you are looking at <unk>. Thank you.
Doug: Yeah, it's a fascinating, really insightful question. The answer is that we think there will be, at some point, both an opportunity and, frankly, a need to have a basket approach. I can tell you that we've gone in, in fact, Dr. O'Neill and I were both presidents at a meeting with the FDA some years ago when we started the dialogue about the potential for a basket approach with our PMO or PPMO technology.
Yeah, just as it really is Sighful question. The answer is that we think there will be at some point.
Both an opportunity and frankly, a need to have a basket approach I can tell you that we've gone in.
Doctor, Neil and I were both president a meeting with the FTA seven years ago. When we started started a dialogue about the potential for a basket approach with our.
<unk> amount of technology. The thing I say the reason that will become important over time is that we can in a very straightforward way just during the kinds of studies studies regarding that which are very lean.
Doug: The thing I say, the reason that it will become important over time, is that we can, in a very straightforward way, just doing the kinds of studies we're doing now, which are very lean and relatively rapid studies, get therapies approved for, you know, up to 50% of the Duchenne community. But if you want to get to that 80% level, if you want to get up to the full opportunity to treat these kids, you're getting into rarer and rarer axons. And it will be in toward that area that we'll have to really think about creating a bad environment.
And relatively rapid studies, we can get therapies approved for bringing up to 50% of the Duchenne community, but if you want to get to that 80% level. If you want to get up to the full opportunity to treat these kids, you're getting into rarer and rarer exercise and it will be in towards that area that will have to really think about creating a.