Q4 2020 Ultragenyx Pharmaceutical Inc Earnings and Corporate Update Call
Good afternoon, ladies and gentlemen, and welcome to the fourth quarter and full year 'twenty 'twenty financial results and corporate update conference call. At this time all participants in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time.
Operator: Good afternoon, ladies and gentlemen, and welcome to the fourth quarter and full year 2020 Financial Results Inc. Update Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star zero. I would like to turn the conference over to your host, Mr. Joshua Higa. Sir, you may begin.
Once you do require assistance during the conference. Please press Star zero.
Like to turn the conference over to your host Mr. Joshua He get Sir you may begin.
Good afternoon, and welcome to the Ultra <unk> financial results and corporate update conference call for the fourth quarter and full year 2020.
Joshua Higa: Good afternoon, and welcome to the Ultragenyx financial results and corporate update conference call for the fourth quarter of full year 2020. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. I am Joshua Higa, Director of Investor Relations, and joining me on this call today are Emil Kakkis, Chief Executive Officer and President, Camille Bedrosian, Chief Medical Officer, Erik Harris, Chief Commercial Officer, and Marty Deer, our Chief Financial Officer.
Issued a press release detailing our financial results, which you can find on our website at ultra <unk> Dot com.
I am Josh when he got a director of Investor Relations for joining me on this call today are Emil <unk>, Chief Executive Officer, and President Camille Bedrosian, Chief Medical Officer, Eric Harris, Chief Commercial Officer, and Marty <unk>, our Chief Financial Officer.
Joshua Higa: I would like to remind investors that this call will include forward-looking statements within the meaning of the state's hardware provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to the types of statements identified as forward-looking in our quarterly report on Form 10-Q that was filed on October 27, 2020, our annual report on Form 10-K that will be filed soon, and our subsequent periodic reports filed with the SEC. These forward-looking statements represent our views only Please note that actual results could differ materially from those projected in any forward-looking statement.
I would like to remind investors that this call will include forward looking statements within the meaning of the seats hardwood provisions of the private Securities Litigation Reform Act of 1995, including but not limited to the types of statements identified as forward looking.
And quarterly report on form 10-Q that was filed on October 27 2020.
Our annual report on form 10-K that will be filed soon and our subsequent periodic reports filed with the SEC, which will all be available on our website from the investors section.
These forward looking statements represent our views only as of the day of this call and involve substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those projected in any forward looking statement for.
Joshua Higa: For a further description of the risks and uncertainties that could cause actual results to differ materially from those expressed in the forward-looking statements, as well as risks related to our business, please see our periodic reports filed with the SEC. I'll now turn the call over to Emil.
For further description for the risks and uncertainties that could cause actual results to differ materially from those expressed on the forward looking statements as well as risks related to our business. Please see our periodic reports filed with the SEC.
I'll now turn the call over to Emil.
Good afternoon, and thank you everyone for joining us today.
Emil D. Kakkis: Good afternoon, and thank you everyone for joining us today. 2020 was a transformative year for Ultragenyx as we executed on many of our strategic priorities. We have now completed the fourth approval from our portfolio we had at IPO, and over the last couple of years, we have now refilled our portfolio with substantial opportunities in six clinical stage programs, four of which are entering pivotal studies. We also have 14 preclinical programs that are advancing our first mRNA program to the clinic this year.
2020 was a transformative year for Altra, Janet as we executed on many of our strategic priorities.
We've now completed the fourth approval from our portfolio, we had at IPO and over the last couple of years, It's now refilled our portfolio with substantial opportunities in six clinical stage programs for which are entering pivotal studies.
We also have 14 preclinical programs that are advancing our first mrna program to the clinic this year.
The efficient conversion of our pipeline to our next opportunities will allow us to accelerate our value creation and treat more rare disease patients with the first ever specific treatment.
Emil D. Kakkis: The efficient conversion of our pipeline to our next opportunities will allow us to accelerate our value creation and treat more rare disease patients with the first ever specific treatment. From a commercial perspective, we achieved the upper end of CRISFIDA revenue guidance despite a global pandemic and received two U.S. approvals and launched treatments for two more diseases with no other approved treatment. From our clinical programs, we released important data updates from our gene therapy programs in GST1A and OTC deficiency, as well as the first glimpse of results for the antisense-alzheimer's guide GTX-102 in Angevin syndrome.
From a commercial perspective, we achieved the upper end and per theater revenue guidance. Despite a global pandemic and receive two U S approvals and launch treatments for two more diseases with no other approved treatments.
From our clinical programs, we released important data updates from our gene therapy programs and G. S. T. One a in OTC deficiency as.
As well as the first glimpse of results for the antisense oligonucleotide Gtx 102 in Angelman syndrome.
Those initial age from results suggest promising activity in this relatively large rare disease with no approved therapies, but certainly much more to do to realize the potential.
Emil D. Kakkis: Those initial results suggest promising activity in this relatively large, rare disease with no approved therapies, but certainly much more to do to realize the potential. On the gene therapy side, we initiated one of the largest ever gene therapy licensing deals by providing non-exclusive rights to Daiichi Sankyo to utilize our manufacturing platform, including our HeLa producer selling technology.
On the gene therapy side, we initiated one of the largest ever gene therapy licensing deals by providing nonexclusive rights to Daiichi sankyo to utilize our manufacturing platform, including our Hela producer cell line technology.
Emil D. Kakkis: Later in the year, we partnered with Solid Biosciences and Duchenne Muscodystrophy to pair their differentiated microdystrophin construct with our AV8 variants and our productive HeLa PCL system. Most recently, we broke ground on and began construction on our gene therapy manufacturing facility in Bedford, Massachusetts, that will initially provide 30 manufacturing runs per year at the 2,000 liter manufacturing scale. Ultragenyx now has one of the broadest gene therapy franchises, which originated from our acquisition of Dimension Therapeutics in 2017.
Later in the year, we partnered with solid Biosciences, and Duchenne muscular dystrophy to per their differentiated microdose drove from construct.
Our 88 variance.
And our productive Hela PCL system.
Most recently, we broke ground and began construction on our gene therapy manufacturing facility in Bedford, Massachusetts.
That will initially provide 30 manufacturing runs per year at the 2000 liter.
Actually scale.
All checks now as one of the broadest gene therapy franchises, which originated from our acquisition of dimension therapeutics in 2017.
Emil D. Kakkis: Our portfolio now includes three in-house pivotal clinical stage programs, one additional clinical program partnered with Bayer, and two publicly disclosed in-house preclinical programs. Our robust HeLa-PCL manufacturing platforms enable us to make AV vectors at large scale. It's a highly efficient, robust process that will enable the next generation of larger clinical programs. But that was just the gene therapy side of the business. Our development strategy is to choose the right modality for each disease, and we have a variety of other therapeutic modes in our portfolio. For genetic diseases of the bone, monoclonal antibodies can be the most effective way of effecting change in their biology.
For now includes three in house pivotal clinical stage program, one additional clinical program partnered with buyer to publicly disclose in house preclinical programs, our robust Hela PCL manufacturing platforms enable us to make 80 vectors at large scale the highly efficient robust process that will enable the next generation of larger clinical.
Programs.
But that was just the gene therapy side of the business.
Our development strategy is to choose the right modality for each disease, and we have a variety of other therapeutic mode in our portfolio.
For genetic disease of bone monoclonal antibodies can be the most effective way for affecting change in their biology.
Emil D. Kakkis: In December, we added a new late-stage monoclonal antibody program via collaboration with Muriel Biopharma. Truzumab, or UX143, has completed a Phase IIb study in adult patients with multiple types of last-chance imperfecta, or OI, which is one of the largest rare genetic bone diseases and significantly more common than XLH. Camille will provide more detail on this program later, but I will note that OI and the UX143 program are a perfect complement for our bone franchise and the expertise we have built with CrisVita.
December we added a new late stage monoclonal antibody program by our collaboration with myriad Biopharma to.
The truth of the Mab or U S. One for three has completed a phase <unk> study in adult patients with multiple types of last chance imperfecta for O I, which is one of the largest rare genetic bone diseases and significantly more common than X L. H <unk>.
Camille will provide more detail on this program later.
But I will note that O I and the U F. One for three program are a perfect complement for our bone franchise and the expertise we have built with Christy to.
Emil D. Kakkis: The learnings from our CrisVita development program will be very helpful in the future development of UX143. Additionally, there is significant overlap between the physicians who treat OI, XLH, and TIO. Importantly, this collaboration provides us with commercial rights to the product throughout the world, with the exception of Europe, where we receive a royalty. While 2020 was a year full of unforeseen challenges, Ultragenyx was able to make substantial progress executing our strategic plan across our pre-clinical, clinical, and commercial programs with great success this past year. I'll hand it over to Erik to provide more detail on our commercial performance for the year.
They're learning from US with field development program will be very helpful. In the future development of UX, one for three and there is significant overlap between the physicians, who treat O Y X H N T I O.
Importantly, this collaboration provides us commercial rights for the product throughout the world with the exception of Europe, where we receive a royalty.
Well I'll do them 'twenty was a year full of unforeseen challenges all genetics was able to make substantial progress executing our strategic plan across our preclinical clinical and commercial programs with great success. This past year.
I'll hand, it over to Eric to provide more detail on our commercial for performance for the year.
Erik Harris: Thank you, Emil, and good afternoon, everyone. I'm truly proud of how the commercial team performed in 2020 in the face of never-before-seen challenges. Twelve months ago, pre-COVID, we issued guidance for crisp meter revenue in our territories of $125 to $140 million. Despite the stay-at-home orders, many doctor's offices temporarily closing for non-essential in-person visits, and all the uncertainty of a global pandemic, we were able to finish the year at approximately $139 million, right at the top end of our guidance.
Thank you Emil.
Good afternoon, everyone I'm truly proud of how the commercial team executed in 2020.
The face of never before seen challenges 12 months ago pre Covid and issued guidance for gross meter revenue non territories of 125 for $140 million.
Despite the stay at home orders, many doctors' offices took really closing some non essential in person visits.
And all of the uncertainty for global pandemic, we were able to finish the year on approximately $139 million right at the top end of our guidance range.
Erik Harris: For 2021, we have issued guidance of $180 to $190 million for Crispeda revenue in Ultragenyx territories. This represents between 30 and 37% year-over-year growth as we enter the fourth year of Crispeda's launch. This steady growth is enabled by the many digital strategies to educate physicians about finding SLH patients and getting these patients on CRISPR while ensuring that existing patients stay on CRISPR during this pandemic. We believe we will continue to see the mix of XLH patients on CRISPR shift towards a greater portion of adult patients.
For 2021, we have issued guidance of $180 million to $190 million for Chris for your revenue and ultra sensitive territories. This represents between 30 and 37% year over year growth as we kind of a fourth year of course heat us launch.
This steady growth is enabled by the many digital strategies to educate physicians and finding patients and getting these patients on for Steve.
While ensuring that existing patients stay on chris' meter during this pandemic.
We believe we will continue to see the mix of XL age patients on price with a shift towards a greater portion of adult patients.
Erik Harris: This will be driven by our increasing efforts to find adult patients by expanding our reach out to more endocrinologists, nephrologists, and other specialties in the community setting. To support these efforts, we will expand both our commercial and medical field teams, who will be focused on these harder-to-find adult XLH patients. In the middle of last year, we launched a TIO indication for CRISPRIDA, and the launch is going very
This will be driven by our increasing efforts on finding adult patients by expanding our reach out more endocrinologists nephrologists and other specialties in the community setting.
To support these efforts, we will expand both our commercial and medical field teams will be focused on these harder to find adult <unk> patients.
In the middle of last year, we launched the tio indication for prestige.
The launch is going very well, we have converted the majority of clinical trial patients to reimburse relative.
Erik Harris: We have converted the majority of clinical trial patients to reimbursed drugs and are receiving star forms for TIO patients from the major metabolic bone center. Reimbursement for TIO is progressing well and is consistent with XLH reimbursement at the same stage of launch. We will not be providing specific patient numbers to TIO, as sales in that indication are included in our overall Proceeder Revenue Guide. Outside of the U.S., we are making steady progress in our discussions with health and reimbursement officials.
Now receiving stock loans for tio patients from the major metabolic bone centers.
Reimbursement for Tio is progressing well and is consistent with X L. A reimbursement at the same stage of launch.
We will not be providing specific patient numbers for G. I L. A.
Sales in that indication are included in our overall, Chris from your revenue guidance.
Outside of the US, we're making steady progress in our discussions with health and reimbursement assistance.
Erik Harris: Demand remains strong across Latin America as we continue to see more and more patients being granted injunctions required to gain access to named patient cells. However, the ordering patterns from the health authorities in this region tend to be inconsistent, leading to some revenue levels that are consistent with other rare disease products in that region. We will keep you updated as we look forward to receiving full reimbursement in other Ultragenyx territories. Moving now to the Joe, it was also launched in the middle of last year for the treatment of long-chain fatty acid oxidation disorders in the United States.
<unk> remained strong across Latin America, as we continue to see more and more patients being granted injunctions required to gain access to named patient sales.
The ordering patterns from the health authorities in this region tend to be inconsistent.
Leading to some revenue lumpiness, which is consistent.
With other rare disease products in that region.
We will keep you updated us we look forward to receiving for reimbursement and other ultra day next territories.
Moving now to the job.
Was also launched in the middle of last year for the treatment of long chain fatty acid oxidation disorders in the United States at.
Erik Harris: At the end of December, we received approximately 190 completed SAR formulas from approximately 90 unique prescribers of Djovi, which speaks to the breadth of interest we are seeing for this product launch from the physician community. This led to approximately 130 patients on reimbursed commercial therapy, which also includes all 80 patients who participated in our clinical study. We are also seeing strong support from payers. As of the end of January 2021, over 100 million lives in the U.S. have digital coverage from over 40 policies, which includes some of the largest national payers.
At the end of December we received approximately 190 <unk> completed start forms from approximately 90 unique prescribers of the Joey which speaks to the breadth of interest we are seeing for this product launch from the physician community.
This led to approximately 130 patients on reimbursed commercial therapy.
Which also includes all 80 patients who participated in our clinical studies.
We are also seeing strong support from payers as for the end of January 2021 over 100 million lives. The us past the jewelry coverage from over 40 policies, which include some on the largest national players.
In these first quarters of the day, the Dolby launch, we will not be providing revenue guidance I believe the start forms and prescriber metrics provide a better sense on the strength of the launch with that I will turn the call over to Marty to share the financial results.
Erik Harris: In these first quarters of the Jobe launch, we will not be providing revenue guidance. I believe the start forms and prescriber metrics provide a better sense of the strength of the launch. With that, I'll turn the call over to Marty to share the financial results.
Thanks, Eric Good afternoon, everyone and thank you for joining today's call.
Maurice Thomas Raycroft: Thanks, Erik. Good afternoon, everyone, and thank you for joining us on today's call. We issued a press release earlier today that included a financial update, which I will briefly summarize. Company revenue for the year ending December 31, 2020 totaled $271 million. Previous revenue in Ultragenyx territories was $138.9 million, including $128.6 million from the North American profit share territory and net product sales of $10.4 million in other regions. Total royalty revenue related to the sale of Crispida in the European territory was $14.5 million.
We issued a press release earlier today that included a financial update which I will briefly summarize.
Company revenue for the year, ending December 31, 2020 totaled $271 million Christy their revenue and ultra Genex territories with $138 9 million, including $128 6 million from the North American profit share territory, and net product sales at $10 4 million.
In other regions total revenue royalty revenue related to the sale of Christy that in the European territory was $14 5 million.
Maurice Thomas Raycroft: The Met SEBI revenue for 2020 was $15.3 million. We expect these revenues may increase modestly over time. The Jolvi revenue for the year was $13 million.
Net savvy revenue for 2020 was 15.39.
We expect these revenues may increase modestly overtime.
Yeah, Joel the revenue for the year with 13 million. This includes approximately five months of revenue after the U S launch it touch all day towards the end of July and the 12 months of named patient sales in other regions.
Maurice Thomas Raycroft: This includes approximately five months of revenue after the U.S. launched Jolvi toward the end of July and 12 months of named patient sales in other regions. 2020 total revenue also includes $89.2 million of non-cash revenue related to the tech transfer services provided to Daiichi Senkyo as part of our strategic manufacturing partnership around the HeLa, PCL, and HEC-293 technologies. Our total operating expenses for the year were $601.1 million, which includes research and development expenses of $412.1 million and SG&A expenses of $182.9 million.
2020 total revenue also included includes $89 2 million of non cash revenue related to the tech transfer services provided to Daiichi sankyo as part of our strategic manufacturing partnership around the Hela PCL on tech to nine three technology.
Our total operating expenses for the year were $601 1 million, which includes research and development expenses of about $412 1 million and SG&A expenses at $182 9 million.
Maurice Thomas Raycroft: In 2021, we expect our R&D costs to increase as we support three pivotal gene therapy clinical studies, the Satrusamab Phase 2-3 clinical study and OI. UX053, our first mRNA Phase 1-2 clinical study in GSD3, and a number of other IND-enabling activities as we get ready to advance the next programs into the clinic. We expect SG&A to modestly increase in 2021 as we continue to support the expansion and launches of Corsita, Dijove, and Mepstevi.
In 2021, we expect our R&D costs to increase as we support three pivotal gene therapy clinical studies.
The truth, the Mab phase three clinical study in O y.
UX nearby three our first mrna phase one two clinical study in GST theory.
On a number of other IMD, enabling activities as we get ready to advance the next programs into the clinic.
That's true SG&A to modestly increase in 'twenty and 'twenty, one as we continue to support the expansion on launches of crispy that agility and that survey.
Maurice Thomas Raycroft: For the year ended December 31, 2020, its net loss was $186.6 million, or $3.07 per share. This compares to a net loss for the same period in 2019 of $402.7 million, or $7.12 per share. The net loss for the year ended December 31, 2020 includes $170.4 million in the fair value of investments in equity security. Net cash used in operations for the year was $132.2 million compared to $345.4 million for the same period in 2019.
For the year ended December 31st 2020, net loss was $186 6 million or $3 seven per share. This compares to a net loss for the same period in 2019 at $402 7 million or $7 from 12 cents per share net.
Net loss for the year ended December 31, 2020 includes $174 million increase in net fair value of investments and equity securities.
Net cash used in operations for the year was $132 2 million compared to 345 4 million for the same period. In 2019, we ended 2020 with $1 2 billion in cash cash equivalents and marketable Securities Inc.
Maurice Thomas Raycroft: We ended 2020 with $1.2 billion in cash, cash equivalents, and marketable securities. This puts us in an excellent position to be able to support the execution of and achieve key milestones in our late-stage clinical pipeline and commercial expansion. Now I'll let Camille touch on some of our clinical programs. Thanks, Marty, and good afternoon, everyone.
It puts us in an excellent position to be able to support the execution of and achieved key milestones in our late stage clinical pipeline and commercial expansion.
Now all that can be I'll touch on some of our clinical programs.
Thanks, Marty and good afternoon, everyone on January eight we issued a comprehensive press release the detailed the latest data regulatory progress and phase III plans for our gene therapy program there.
Camille L. Bedrosian: On January 8, we issued a comprehensive press release that detailed the latest data, regulatory progress, and phase three plans for our gene therapy program. Therefore, today, I will briefly summarize our current status and next steps for our three pivotal stage gene therapy program. DTX-401 for glycogen storage disease type 1a has completed the scientific advice process with the European Medicines Agency, or EMA, as well as held an end-of-phase 2 meeting with the FDA. Based on these meetings, we have aligned on the Phase 3 study design and endpoints.
Therefore today I will briefly summarize our current status and next steps for our three pivotal stage gene therapy programs.
D T X for one for glycogen storage disease type one he has completed the scientific advice process with the European medicines agency or EMA as well as held an end of phase two meeting with the F. D. A.
Out of these meetings, we have aligned on the phase III study design and endpoints we.
Camille L. Bedrosian: We currently are on track to initiate this pivotal study in the first half of 2021. Moving now to DTX-301 for ornithine transcarbamylase, or OTC deficiency We have received feedback from our initial scientific advice discussions with the ENA and will have an end-of-phase 2 meeting with the FDA, barring any unforeseen delays, by the end of this quarter. Based on these initial discussions, we feel confident about where we will end up with regard to the design and endpoints for this Phase 3 study.
We currently are on track to initiate this pivotal study in the first half of 'twenty 'twenty one.
Shifting now to D. T X T O one for ornithine, <unk> or OTC deficiency.
We have received feedback from our initial scientific advice discussions with the E. N E. On will have an end of phase two meeting with the FDA barring any unforeseen delays by the end of this quarter.
Based on the initial discussions we feel confident about where we will end up with regards to the design and endpoints for this phase III study.
Camille L. Bedrosian: We currently are on track to initiate this study in the second half of 2021. Moving now to UX701 for Wilson disease, our third pivotal gene therapy program to enter the clinic in 2021. Earlier this year, we announced that the seamless, single-protocol Phase 1-2-3 IND application has cleared FDA review. The program also recently received FastTrack designation, which will enable additional dialogue and feedback from the FDA.
We currently are on track to initiate this study in the second half of 'twenty 'twenty one.
Moving now to U S 701 for Wilson disease, our third pivotal gene therapy program to enter the clinic in 'twenty 'twenty one.
Earlier this year, we announced that the seamless single protocol Phase 123, I N D application has cleared F T a review.
The program also recently received fast track designation, which will enable additional dialogue and feedback from the F. D. A.
Camille L. Bedrosian: This study currently is on track to initiate in the first half of 2021. Now I'll touch on GTX 102, an Antisense Oligonucleotide which is being developed with our partner Genetics for the treatment of Angelman Syndrome. Angelman Syndrome is a devastating neurogenetic disorder with a broad spectrum of disease manifestations, including speech and cognitive impairments, Ataxia, or balance issues.
This study currently is on track to initiate in the first half of 'twenty 'twenty one.
Now I'll touch on Gtx, one O two.
On the anti sense, oligonucleotide, which is being developed with our partner <unk>.
<unk> for the treatment of Angelman syndrome.
On a syndrome is a devastating neuro genetic disorder with a broad spectrum of disease manifestations, including speech and cognitive impairment.
Taxi on our balance issues sleep dysfunction and seizures.
Camille L. Bedrosian: Sleep Dysfunction and Seizures, GTX-102 is the first antisense oligonucleotide program for Angelman to reach the clinic. Late last year, we announced positive interim data from the ongoing Phase 1-2 study of DTX-102. All five patients who were treated demonstrated improvements in at least three disease domains and scores of much improved or very much improved in two disease domains as measured by the Clinical Global Impression of Improvement Scale for Angelman Syndrome. These improvements were also supported by other increases in measures, including Observer-Reported Communication Ability, or ORCA, and Bayley-4 communication scales, as well as by preliminary EEG readings.
Gtx, one owe to us the first antisense oligonucleotide type program for Angelman to reach the clinic.
Late last year, we announced positive interim data from the ongoing phase one two study of Gtx one O to.
All five patients who were treated demonstrated improvement in at least three disease domains and scores of much improved or very much improved in two disease domains as measured by the clinical global impression of improvement scale for Angelman syndrome.
These improvements were also supported by other increases that measures, including observer reported communication ability or orca and daily for communication scales as well as by preliminary E. G reading.
All five patients also had a grade one or two serious adverse event of lower extremity weakness associated with local inflammation in the region of administration and the lower back at the higher doses of Gtx 102.
Camille L. Bedrosian: All 5 patients also had a grade 1 or 2 serious adverse event of lower extremity weakness associated with local inflammation in the region of administration in the lower back at the higher doses of GTX-102. Dosing was paused after the first SAE onset was observed, and the study is currently on clinical hold. The SAE has fully resolved in all five patients, and clinical improvements have been sustained beyond the resolution of the SAE.
Dosing was paused after the first S. H E onset was observed in the study is currently on clinical hold.
The SAE has fully resolved and all five patients and clinical improvements have been sustained beyond the resolution of the S. H E.
Genetics, our partner has submitted to the F. D. A substantial information amendment, including follow up safety information for the five patients dosed and non clinical data in nonhuman primates.
Camille L. Bedrosian: Genetics, our partner, has submitted to the FDA a substantial information amendment, including follow-up safety information for the five patients dosed and non-clinical data in non-human primates. We have proposed an amended dosing and administration plan to the FDA. These changes are expected to reduce the local contact time and concentration of the ASO.
We have proposed an amended dosing administration plan to the F D. A.
These changes are expected to reduce the local contact time and concentration of the a S. L.
Camille L. Bedrosian: Furthermore, the new dosing plan is within the observed range of clinical activity but well below doses associated with SAE. Genetics received some questions from the FDA, and responses were provided. We currently expect the study to resume enrollment and dosing in the first half of 2021 following resolution of FDA requests and approval to proceed. Once restarted, we expect additional interim data from the study, which is expected in the second half of 2021. We are also in the process of expanding the study to other countries, including Canada, where a clinical trial application was previously filed. A protocol and information amendment similar to that proposed to FDA will be submitted.
Furthermore, the new dosing plan is within the observe range of the clinical activity, but well below doses associated with us a east.
And that has received some questions from the F D. A and responses were provided.
We currently expect the study to resume enrollment and dosing in the first half of 'twenty 'twenty. One following resolution of F. D. A request and approval to proceed.
Once we started we expect additional interim data from this study.
That are expected in the second half of 'twenty 'twenty one.
We are also in the process of expanding the studies for other countries, including Canada, where our clinical trial application was previously filed a protocol and information amendment similar to that proposed to F. D. A will be submitted.
Our fourth pivotal program to enter the clinic in 'twenty 'twenty, one will be the UX, one for three or so to us a map.
Camille L. Bedrosian: Our fourth pivotal program to enter the clinic in 2021 will be UX143 or Citrusamab, a monoclonal antibody for the treatment of osteogenesis in Profecta or OI through our partnership with Moreo. OI is an extremely serious bone disease where a defect in collagen results in significant bone fragility leading to stiffness, pain, fractures, and deformity. Oftentimes, OI is believed to be a result of weak collagen. But based on our sponsored preclinical work and others' research, we now understand that the major cause of bone weakness in OI is due to excessive bone resorption triggered by the abnormal collagen and the inadequate production of new bone, leading to low bone mass. These data show that if you could simply increase bone formation and reduce excessive bone resorption, you can increase bone density and improve bone strength, even with abnormal collagen, and achieve improved fracture prevention.
Monoclonal antibody for the treatment of osteogenesis imperfecta or O I to our partnership with morale.
O I has an extremely serious bone disease, where a defect in collagen resulted in significant bone fragility, leading to stiffness pain fractures and deformities.
Oftentimes Oh I is believed to be a result of weak collagen, but based on our sponsored preclinical work and others research. We now understand that the major cause of bone weakness NOI is due to excess bone resorption triggered by the abnormal collagen.
And the inadequate production of new bone, leading to low bone mass.
These data show that if you could simply increased bone formation and reduce the excessive bone resorption, you kind of increased bone density and improved bone strength, even with the abnormal collagen.
And achieve improved fracture prevention.
Camille L. Bedrosian: We believe this is the insight that could change the future for patients with OI. Moreo has released Phase II data in 90 adult patients with OI, randomized among three different dose levels. The patients were dosed monthly for 12 months. Study results indicated substantial improvements in bone mineral density in OI types 1, 3, and 4, the three types included in the study. This response was dose-dependent and observed across different anatomical sites.
We believe this is the insight that could change the future for patients with O I.
Mario has released phase two data in 90 adult patients with O Y randomized among three different dose levels.
Patients were dosed monthly for 12 months.
Study results indicate us substantial improvements in bone mineral density and Oh, why types of one three and for us.
Three types included in this study.
This response was dose dependent and observed across different anatomical sites.
Camille L. Bedrosian: The study also showed an ability to create a significant amount of bone, which we believe is a very important factor in improving bone strength. The safety profile of citruzumab was favorable for patients with OI. Pending discussions with regulatory agencies, we are planning to enroll a Phase II-III study in pediatric patients. The first will identify the optimal dose based on increases in the serum bone formation marker, P1MP, and then roll into a randomized control period looking at fracture rate reduction and bone mineral density over an estimated 15 to 24 months.
The study also showed an ability to create a significant amount of bone, which we believe is a very important factor.
<unk> factor in improving bone strength.
The safety profile for us it to us and that was favorable for patients with Hawaii.
Pending discussions with regulatory agencies, we are planning to enroll the phase two three study in pediatric patients. The first of all identify the optimal dose based on increases in the Sierra on bone formation marker people on M. P. And then roll into a randomized control period looking at fracture rate reduction and bone mineral.
Density over an estimated 15 to 24 months.
Camille L. Bedrosian: While a separate pivotal study also is being planned for adults with OI, we believe the pediatric population will give us the fastest avenue for approval for the product. We currently expect to initiate the Pediatric Phase 2-3 study in the second half of 2021. The last program I will briefly summarize is UX-053 for collagen storage disease type 3, or GSD-3. GSD3 is an inborn error in metabolism caused by mutations in the AGL gene, which is responsible for the production of the glycogen debrancher enzyme.
Well, let's separate pivotal study also is being planned for adults with Oh, why we believe the pediatric population will give us the fastest avenue for approval for the product.
We currently expect to initiate the pediatric phase two three in the second half of 'twenty 'twenty one.
The last program I will briefly summarize is U X O five three for college and storage disease type three or G. S. D. Three.
G. S. D. Three is an inborn error of metabolism caused by mutations in the a G. L gene, which is responsible for the production of the glycogen day branch for enzyme a day.
Since its a deficiency of the debenture enzyme impairs the breakdown of glycogen in the liver and leads to a toxic residual carbohydrate.
Camille L. Bedrosian: A deficiency of the debrancher enzyme impairs the breakdown of glycogen in the liver and leads to toxic residual carbohydrate. Through our license from Arcturus, we have developed an mRNA and lipid nanoparticle product that is intended to restore debrancher enzyme function, thereby clearing the accumulated toxic residual carbohydrate and normalizing glycogen metabolism in the liver. We are currently on track for an IND in the first half of 2021 and to initiate a Phase I-II study in the second half of the year. I'll now turn the call back to Emil to wrap up.
Two our license from Arcturus, we have developed an mrna and lipid nanoparticle product that is intended to historic day branch for enzyme function, thereby clearing the accumulated toxic residual carbohydrate and normalizing glycogen metabolism in the liver.
We are currently on track for an I N D and the first half of 'twenty 'twenty, one and to initiate a phase one two study in the second half of the year.
I'll now turn the call back to Emil to wrap up.
Thanks, Camille Marty and Eric 2021 is going to be a full year lots of important progress across our commercial and clinical programs.
Emil D. Kakkis: Thanks Camille, Marty, and Erik. 2021 is going to be a full year with lots of important progress across our commercial and clinical programs. The active work in BD has refilled the pipeline with multiple late-stage catalysts and one of the best rare disease portfolios in the business. In the commercial portfolio, we're looking forward to continuing expanding CRIS-V in the adult market through greater efforts to find patients in outlying clinics and through pedigree analysis. We're also continuing to expand CRISV to use outside the US, Latin America, Canada, and Turkey.
The active work in BD has refilled the pipeline with multiple late stage catalysts with one of the best Weird for these portfolios in the business.
On the commercial portfolio, we're looking forward to continue expanding proceeded in the adult market through greater efforts to find patients in outlying clinics and through pedigree analysis.
We're also continuing to expand because for you to use outside the U S Latin America, Canada and Turkey.
Emil D. Kakkis: Giljovi is off to a strong start, and I know the team will continue to execute the launch for patients with LC-FAOD who are in great and urgent need of a new treatment option. Our commercial medical teams have adapted very well to launching three products and four diseases in the COVID environment. Within our gene therapy business, we've broken ground on the manufacturing facility in Bedford, Massachusetts. We have three programs going into late-stage clinical trials. We continue to advance our early stage work in neuromuscular disease, CDKL5 deficiency, and Duchenne muscular dystrophy.
Well drove us off to a strong start and I know the team will continue to execute one for patients with L. C. F. O D. We're in great an urgent need for a new treatment option.
Our commercial Medicare seems have adapted well very well to launching three products and for disease in the Covid environment.
Within our gene therapy business, we've broken ground on the manufacturing facility in Bedford, Massachusetts for three programs going on at least late stage clinical trials.
Continued advance our early stage work in your muscle disease, a C D Cal fire deficiency, and Duchenne muscular dystrophy.
Emil D. Kakkis: We're also continuing to improve on the Helium Manufacturing Technology with the new 3.0 system that will have even higher productivity and reduce COGs, making gene therapy a viable modality for these larger, higher-dose indications on a global basis. Our Nucleic Acid Therapeutics Pipeline will also advance. We're making progress in resuming the ASO Phase 1-2 study in Angeman. We plan to initiate clinical development for the mRNA-UXO53 and Flexion Score Disease Type 3, or Debranched or Deficient, was our first mRNA program to come out of our lives with our courage.
We're also continue to improve on the Hela manufacturing technology with the new three point O system.
We'll have even higher productivity and reduce Cogs, making gene therapy on bio modality for these larger higher dose indications on a global basis.
Our nucleic acid therapeutics pipeline will also advance we're making progress on resuming is so phase one two study and the instrument we plan to initiate clinical development for the mrna you X O five three in <unk>.
Collection store disease type three or D branch for deficiency.
For their first mrna program to come out of our licenses our tourists.
Emil D. Kakkis: That license also provides rights for up to 12 mRNA and other nucleic acid therapy targets. The GSD-3 program is also a great complement to our efforts in GSD-1a and builds on our broader portfolio of therapies aimed at inborn errors of metabolism that have not been treated by more traditional means. The addition of citruzumab gives us a de-risk late stage program that will leverage our expertise in creating clinical development pathways for rare genetic bone diseases.
That license also revise rights for up to 12 mrna and other nucleic acid therapy targets.
The <unk> three program is also a great complement to our efforts in GST, one day and builds on our broader portfolio of therapies aimed at inborn errors of metabolism that have not been treated by more traditional means.
The addition of for truth Mab gives us a derisk late stage for them that liberal or leverage our expertise.
Clinical go on pathways for rare genetic bone diseases.
As you can see we're in a great moment in our evolution for the company with multiple late stage assets across therapeutic areas and modalities all enabled by.
Emil D. Kakkis: As you can see, we're in a great moment in our evolution as a company, with multiple late-stage assets across therapeutic areas and modalities, all enabled by continued strong financial performance from our approved programs, strategic investing, and fiscal diligence. Now, let's move on to your questions. Operator, please provide the instructions for the Q&A portion of the call.
Our continued strong financial performance from our Peru program strategic investing in physical diligence.
Now, let's move onto your questions. Operator, please provide the instructions for the Q&A portion of the call.
Thank you, Sir ladies and gentlemen, if you have a question at this time. Please press the star one on there the number one key on your Touchtone telephone we only allowed one question and one follow up question for each participant to give chance to other participants to ask a question respectively.
Operator: Thank you, sir, ladies and gentlemen. If you have a question at this time, please press the star 1 under the number 1 key on your touchtone telephone. We only allowed one question and one follow-up question for each participant to give a chance to other participants to ask the question respectively. If your question has been answered or you wish to remove yourself from the queue, please press the pound. Your first question comes from the line of Maury Raycroft from Jeffreys. Your line is open.
Question has been answered or you wish to remove yourself from the queue. Please press the pound key.
Your first question comes from the line of Mario Raycroft from Jefferies. Your line is open.
Unknown Executive: Hello, Maury. Are you there, Maury? Well, that's a very good question. We are doing great, and thank you for asking.
Hello Maury.
Are you there Maury.
Well, that's a very good question.
We are doing great and thank you for asking.
Unknown Executive: Maury, maybe you're on mute. Operator, why don't we go on to the next caller? Until Maury gets his vacations fixed.
Where are you maybe you're on mute.
Operator, when we go on to the next caller.
Until he gets us vacation fixed.
Operator: [inaudible] Your next question comes from the line of Yaron Werber from Colwyn. Your line is open. Hey, good afternoon.
Yes, Sir your next question comes from the line of Yaron Werber from Cowen Your line is open.
Hey, good afternoon. Thanks for taking my question. So Emil I got maybe the first question. The pipeline is now looks really good what does that mean youre essentially to join us going into pivotal is another one for potentially into a phase two three I mean, it's fairly full do you have more room for BD or are you still looking or are you sort of good for them.
Yaron Benjamin Werber: Thanks for taking my question. So Emil, I have maybe the first question: the pipeline now looks really good, right? I mean, you have essentially two drugs going into pivotals, another one potentially into phase two, three.
Yaron Benjamin Werber: I mean, it's fairly full. Do you have more room for BD? Are you still looking? Or are you sort of good for the next year? And then Marty, I don't know if you can give us any sense. How do we model Daiichi-related revenues? Do you have visibility you could share with us? Thank you.
Next year, and then Marty I don't know if you can give us any sense, how do we model Dai Ichi related revenues do you have visibility that you could share with us. Thank you.
Great your own I think.
Emil D. Kakkis: Great, Yaron. If you look at our portfolio, we tend to target having 5 to 7 clinical stage programs, and right now, we would have 6 with what we're doing, so we're in a relatively full state in terms of development stage programs. We are still continuing to do BD because we always continue to look. If there were something amazing, we wouldn't want to walk past it.
If you look at our portfolio, we tend to target, having five to seven clinical stage programs and right now we would we'd have six with what we're doing so we're we're in a relatively full state in terms of development stage programs.
We are still continuing to BD because you always continue to look if there were something amazing you wouldnt want to walk past it we would look for that opportunity.
Emil D. Kakkis: We would look for that opportunity, but we potentially have the ability to leverage our commercial organization with a later stage opportunity. But I do believe from an earlier development stage, our opportunities were very full. We've been off, and we've got a lot of work to do, and I'm excited about the portfolio. I don't think you can imagine being in a better place than what we've been able to put together over the last couple of years. So Marty, maybe you can answer the other question.
But we arent potentially have ability to leverage our commercial organization with a later stage of opportunity.
But I do believe him from earlier development stage opportunities, where we're very full we'd been on wharf and we've got a lot of work to do and I'm excited about the portfolio I don't think you can imagine being in a better place than what we've been able to put together over the last couple of years for Marty maybe you can answer the other question yeah.
Maurice Thomas Raycroft: Yeah, real simply, Yaron, with Daiichi, of course, the deal that we completed back in March was for $200 million up front from an accounting perspective. We have this non-cash revenue recognition that we believe is associated with the tech transfer of the deal. So there's about $60 million plus left on that recognition of revenue, and that should be complete in 2021. So that should be a pretty specific way to model it in 2021.
Yeah real simply your own with Daiichi them of course.
That we completed back in March was for $200 million upfront from an accounting purpose. We have this non cash revenue recognition that we believe is associated with the tech transfer of the deal. So theres about 60 million plus left on that.
That recognition of revenue and that should be complete in 2021, so that should be a pretty specific way to model. It in 2021.
Great. Thank you.
Yaron Benjamin Werber: Great, thank you. Your next question comes from the line of Gena Wang from Barclays. Your line is open.
Yep.
Your next question comes from the line of Gena Wang from Barclays. Your line is open.
Gena Wang: Thank you for taking my questions. I have two questions. One is regarding Angelman Syndrome. It seems that FDA has already given you feedback, and I'm just wondering if you can give a little bit more color regarding the amendment to the protocol. You know, is there any additional change versus your original submission regarding the protocol amendment? And my second question is regarding the dosing change. You know, you used DD-PCR for the GSD-1A pivotal study, and it changed the dose from 6E12 to 1E13. I'm just wondering, do you need to make a similar change for the OTC program? And will you use DD-PCR across all the future programs so that the dosing will be more accurate going forward?
For taking my questions I have two questions. One is regarding the end human syndrome.
It seems that you already give you feedback and Emil just wondering if you can give a little bit more color regarding the amendment to the protocol.
Is there any additional change versus your original submission regarding the protocol Amendment and my second question is regarding the.
Dosing change you know you us DD PCR for the GSD by a pivotal study and it changed the dose from <unk> 12 to <unk> I'm. Just wondering do you need to do similar change for the OTC program and will you use DD PCR across all the future program. So that the dosing will be more active.
Going forward.
Emil D. Kakkis: On the Angelman, we gave them this very large, substantial amendment. They then provided a response with some specific questions, additional information, and inquiries that they were interested in. Those questions did not change the plan we had proposed. We listened to what they put together and provided now an amendment to the protocol and IAB, et cetera, and all the things required in order to proceed ahead. So we'll wait and see their response to that, but the questions didn't really change our plan. They were basically in line.
Sure Great. So on the Angelman, we gave him this very large substantial amendment. They provided then a response with some specific questions additional information.
Wiry.
On that they were interested in those.
For those questions did not change the plan we had proposed.
We listen to what they put together and provided now.
And the amendment to the protocol and IV et cetera on all the things required in order to proceed ahead. So we'll wait and see their response to that but the questions didn't really change our plan they were.
Basically in line I think we our plan that's true it's pretty well thought out I don't think that there is.
Emil D. Kakkis: I think our plan was pretty well thought out. I don't think that there is. I think there's not much you can do to change it, but we'll wait and see for their feedback. There may be subtle ways to manage it, and they will want to assure safety just like we do, and we're happy to work with them to get that done. We feel comfortable. We're gonna get back into treating these patients, and the patients have been inquiring. They really want to get back to treatment, so we're... We want to get back to it. I think we're in good shape for that, and we'll see what they say.
I think there's not much you can do to change it, but we'll wait and see for their feedback from may be subtle ways to manage it and they will want to assure safety just like we do and we're happy to work with them to get that done, but we feel comfortable we're going to get back into treating these patients and the patients are enquiring, they really wanted to get back to treatment. So we're.
We wanted to get back to it I think we're in good shape for that and we'll see what they say.
Emil D. Kakkis: On the GST-1 story, we're not really changing the dose. What we're doing is changing how we're measuring the dose. So it's really important.
On the GST one story, we're not really changing the dose what we're doing is changing how we're measuring the dose.
So what so it's real important on the total doses for giving us the same as it was before it's just what we're calling it has changed and what what's happened is that the original Q PCR methods have some limitations and variability in them, they're not us is good and we've been working on the.
Emil D. Kakkis: The total dose effect we're giving is the same as it was before. It's just what we're calling it has changed. And what's happened is that the original qPCR methods have some limitations in variability in them. They're not as good.
Emil D. Kakkis: And we've been working on the digital drop method, which is higher, more reproducible, more validatable, and therefore a more accurate representation. And what it turned out for GST-1a is that the amount of vector we were giving, which we considered 6E12 before, was actually closer to E13 when you use a more accurate digital drop method. And it just relates to the techniques and the biases of certain techniques.
Digital drop method, which is hire more reproducible more validated bowl and therefore, a more accurate representation of what it turned out for GSD. One day is that we were really the amount of vector, we're giving which we considered 60 12 before it was actually closer to <unk>.
When you use them more accurate digital drop method.
And it just relates to the techniques and the the biases of certain techniques for the OTC program. There is also a difference and we are using the double digital drop but would it be clear to everyone is that the dose is the same as it was it's just what we're labeling the dose as based on a more accurate method.
Emil D. Kakkis: For the OTC program, there is also a difference, and we are using the digital drop. But what would be clear to everyone is that the dose is the same as it was. It's just what we're labeling the dose as based on a more accurate method. And this is one of the things I think the FDA has been working on, and we all want, to continue to improve the quality of the methods to give us... Practically speaking, it doesn't change anything, but from a standpoint of the quality of the process, it helps give FDA and ourselves confidence in what we're administering at every launch.
And this is one of the things I think the FDA has been on and we all want us to continue to improve the quality of the message to give us.
Accurate representations of how many of these particles are alive and well in the vector product that we can use for gene therapy. So.
Practically speaking it doesn't change a thing but from a standpoint of.
Corey Kasimov: Great, thank you. Your next question comes from the line of Corey Kasimov from J.P. Morgan. Your line is open. Hey, good afternoon, guys. Thanks for taking the questions. First one on Angelman, assuming you do, in fact, get that study up and running in the first half of the year, as you're expecting, how quickly do you think you'll know whether the amended dosing and administration plan is working and avoiding the FAA?
The quality of the process. It helps give the FTA and our self confidence on what we're administering February lot.
Great. Thank you.
Your next question comes from the line of Cory <unk> from Jpmorgan. Your line is open.
Hey, good afternoon, guys. Thanks for taking the questions.
First one on Angelman and assuming you do in fact get that study up and running in the first half for the year as Youre expecting how quickly do you think you'll know whether the amended dosing and administration plan is working and avoiding the US as you saw originally and then I have one follow up on us on wells.
Emil D. Kakkis: Avoid any SAEs you saw originally, and then I have one follow-up on Wilson. Well, the way the protocol is proposed, we will redose the existing patients, the five patients, and we'll also enroll another 12 patients in a staged manner and look at basically four doses, and then they'll go into maintenance every three months. So by the time we get through four months of dosing with these patients, in both the five and the additional 12, that will give us a sense of, are we getting the efficacy we thought after accumulating the effect over multiple doses at a lower level? And are we seeing safety?
Yes.
Well the way the protocol, it's proposed that will we will re dose the existing patients for five patients and will also enroll.
Now, they're 12 patients in a staged manner.
And look at basically for doses and then they'll go into a maintenance every three months. So by the time, we get through four months of dosing with these patients.
In the fall for five and the the additional 12 that will give us a sense of are we getting the efficacy we thought after accumulating the effect over a multiple doses at a lower level and are we seeing safety. So we'd expect to get to that story later in the year because it takes about four months for each page.
Emil D. Kakkis: So we'd expect to get to that story later in the year because it takes about four months for each patient enrolled to get through the doses. So if we can get through four doses and show the same substantial efficacy we saw before and not have a safety event, that helps improve it. Once they go on to maintenance, where they're going every three months for dosing, I think we feel a little more comfortable that the safety will be better.
For enrolled to get through the dosing. So we can get through for doses and show the same substantial efficacy we saw before and not have the safety event that helps improve it once they go on to maintenance what are they going every three months dosing.
I think we feel a little more comfortable that the safety will be better. The problem. We had was only during the monthly sales. So if we can get through the monthly phase go on to maintenance dosing and are good through the monthly phase and get the efficacy. We're hoping for them I think we'll know and that should happen later this year.
Emil D. Kakkis: The problem we had was only during the monthly phase. So if we can get through the monthly phase, go on to maintenance dosing, and are good through the monthly phase and get the efficacy we're hoping for, then I think we'll know, and it should happen later this year. Okay, that's very helpful.
Okay. That's very helpful. And then for your Cmos Phase 123 for Wilsons whats the process in terms of making a go no go decisions here to move to the next stage in this particular type of design is it should we think of it just has it truncated study across all three typical phases or is there something else that goes into it.
Corey Kasimov: And then for your Seamless Phase 1, 2, 3 for Wilson's, what's the process in terms of making go, no-go decisions here to move to the next stage in this particular type of design? Should we think of it just as a truncated study across all three typical phases, or is there something else that goes into it?
Well, the there's two stages and stage one we're gonna dose plus.
Emil D. Kakkis: Well, there are two stages. In stage one, we're going to go... A placebo and drug in three cohorts, a first dose cohort, 5E12, E13, 2E13, alright so it's going to be a sequence of patients through three cohorts. During this period, there will be an interim assessment, a blinded interim assessment to show what the dose is looking like and what's happening, and we'll make a decision on dose after those three cohorts. At that point, we would know in a blinded fashion in groups that we're seeing an efficacy and safety that's appropriate, and we will pick the dose to move forward.
Placebo and drug in three cohorts, a first dose cohort 512, <unk> to eat 13th Alright, So it's gonna be a sequence of patients through three cohorts during.
During this period, there will be an interim assessment, a blinded or interim assessment to show whether the what the dose is looking like and what's happening and we'll make a decision on dose. After those three cohorts at that point, we would know in a blinded fashion and group that we are seeing an efficacy on safety, that's appropriate and we'll pick the dose to move from.
Forward, so we'd expect somewhere in there to have some data that we would put out that would not but we want to make sure not to harm the conduct of the study, but will put out some information about where we stand in that we've crossed from the dosing stage into the pivotal stage does that helpful.
Emil D. Kakkis: So we'd expect somewhere in there to have some data that we would put out that would not, but we want to make sure not to harm the conduct of the study, but we'll put out some information about where we stand and that we've crossed from the dosing stage into the pivotal stage. Is that helpful?
Corey Kasimov: Yeah, definitely. Thanks, Emil. I appreciate it.
Yeah, it's definitely thanks, Sam I appreciate it.
Your next question comes from the line of Jin leave from Trust Securities You May ask your question.
Joon So Lee: Your next question comes from the line of Joon Lee from Thrift Securities. You may ask your question here. Hi, thanks for taking my questions. So, Emil, can you affirm that the FDA was generally in agreement that Cannellenberg and lower doses would be sufficient to avoid the SAEs, or did they want something entirely different? And then secondly, what, if any, reason is there for the failure of OB-101 in Angelman? Is the placebo effect possibly an issue when using CGIIS? Just curious if there's anything that can be learned from that study to apply to your study.
Hi, Thanks for taking my questions.
So can you affirm that the FDA was generally in agreement that tend ellenberg and lower dosing will be sufficient to avoid the ease or do they want something entirely different and then secondly, what if any lease is there from the failure of Ob one O. One in Angelman is us.
Placebo effect, possibly on issue when using C. T. I just curious if there's anything that could be learned.
From that study to apply to yourself. Thank you.
Emil D. Kakkis: Sure, well, the FDA did not question Trendelenburg and Flush, the procedures, because actually, they've been used widely, and I think we provided justification for that, because it's been done, by the way, in chemotherapy for years, years. It's not like we made this up.
Sure well.
He did not question the trend on mergen flush the procedures because actually they have been used widely and I think we provided.
The justification for that because it's been done by the way in chemotherapy for years and years, it's not like we made this up it's been well established to reduce local toxicity in chemotherapy drugs. So it's not like we're it's something that's never been done before but it wasn't really questioned about that it was more about what the event is and you know what's going on kind of thing.
Emil D. Kakkis: It's been well-established to reduce local toxicity in chemotherapy drugs, so it's not like we're doing something that's never been done before. But there wasn't really a question about that.
Emil D. Kakkis: It was more about what the event was and, you know, what's going on kind of thing. Just, they just want confidence around that we can make the right interpretation of what's happening and our interpretation of it being a local inflammatory event. And those required just more detailed information about the MRIs and other things so they could kind of understand what we understand. So there was no question about the strategy of lower dosing, capping, and the other changes at this point. So we feel pretty good about where we're at. I do think we're making the right choices.
They just want confidence around the we can make the right interpretation of what's happening in our interpretation of it being a local inflammatory event.
And those required but it's just more detailed information about the MRI and other things. So they can kind of understand what we understand so there was no question about the strategy on lower dosing tapping in and the other changes at this point so we.
We feel pretty good about where we're at I do think we're making the right choices and I think there's a good basis for our changes to be beneficial.
Emil D. Kakkis: And I think there's a good basis for our changes to be beneficial. Now, with regard to OVID-101, I don't think it has too much read-through. If it was, of course, an approved product during our Phase 3, it would probably create more complexity for how we're managing patients on it or not on it. In regard to CGI and its value, I appreciate the fact that our five patients were on open-label. The magnitude of the effect that we're seeing is not 0.7 points, where the average for the five patients was 2.4 points.
And with regard to open one on one I don't think it has too much read through it if it was of course, an approved product during our phase three it would probably create more complexity for how we're managing patients on it or not on it.
With regard to CGI and its value I. Appreciate the fact that our five patients were open label the magnitude of the effect that we're seeing is not 0.7 points remember the average for the five day. She was two point for point. So the degree of efficacy changes far larger than you might see from placebo at that.
Emil D. Kakkis: So the degree of efficacy change is far larger than you might see from placebo if that was placebo. In addition to that, there were multiple other evaluations in the trial that supported the communication changes and other changes observed, including sleep and other things, including mobility. So it wasn't just CGI.
Was placebo.
Effect. So in addition to that there were multiple other evaluations in the trial that supported the communication changes and other other changes observed including sleep and other things including mobility.
So it wasn't just T. G. I was actually a whole host of secondary valuations also supporting the change. So that's why we know this is real and we know it's profound and we were.
Emil D. Kakkis: It was actually a whole host of secondary evaluations also supporting the change. So that's why we know this is real, and we know it's profound.
Emil D. Kakkis: You know, we think it's something that could be quite important for these patients. And we know, by the way, that as time is passing, of course, the patients will. The defect lasted maybe four or five months in many of the symptoms, but as time has passed, of course, patients... have lost some ground and are anxious to get started again. So in our case, I'm 100% confident this is not the placebo effect. We have too much data to support it. And, of course, the magnitude of the effects is just beyond what you would. It is assumed to be part of a placebo effect.
We think its something could be quite important for these patients.
Well you know by the way that with the time us passing for us the patients have.
The effect lasted maybe for five months in and many of us symptoms, but it's true.
It's passed of course patients have lost some ground in.
Are anxious to get started again so in our case.
I'm, 100% confident this is not a placebo effect, we have too much data to support it.
And of course, the Max it affects just beyond what you would assume to be part of a placebo effect.
Joon So Lee: And just just quickly following up on the Angelman's, you know, you have now created a target for yourself. You know, there are companies pursuing the exact same approach. Stop. What kind of notes do you have around your product?
And just just quickly following up on the Angelman. You know you have now created a target for yourself.
Companies pursuing the exact same approach stopped us stop what what kind of nodes do you have around your product.
Joon So Lee: that could protect the franchise from being well better.
That could protect the franchise for us well.
Emil D. Kakkis: Well, I think you've got to target make the first thing you've got to run fast. So they're hard to hit, but that's sort of facetious but truthful, too.
Well I think you've gotta targeting back the first thing is you've got to run fast for.
For their hard to hit but that's.
That's sort of facetious, but truthful to I think our ability to execute is going to be real important.
Emil D. Kakkis: I think our ability to execute is going to be really important. The truth is, if you want to... As a company, we will work on some larger rare disease areas, but when we do, it's not going to be all alone like some other ones like OTC, GST-1, GST-3. This, it's more comfortable.
The truth is if you wanted us.
As a company we will work on some larger rare disease areas, but when we do it's not going to be all alone like some other ones like the OTC GSD one GST three.
It's more comfortable we really pretty much the only clinical play.
Emil D. Kakkis: We're really pretty much the only clinical play. It'll be there, but here's the thing about the whole program. The reason we picked this Angeman program, the work GenX had done, is that we had the data that we were looking at that they produced in vitro and others, all the work Scott did, which said what they're doing and the region they're targeting is far more important, able to knock down all the antisense transcripts than what other people are doing. And it's what we felt there was a distinct intellectual property, scientific insight. And you can't have variations of expression on this thing. They're too high.
It'll be there, but here's the thing about the whole program. The reason we picked this angelman program. The work gets done is that we had the day there that we were looking at that they produced in vitro and others on all the work's gone did a debt, which said what they're doing in the region, they're targeting us far more partner able to knock down on.
All the antisense transcripts than what other people are doing is we felt there was a distinct intellectual property scientific insight.
Improvement the other methods trying to do what we're doing is actually very hard I do think the us fill method will be better for the gene therapy will be hard to replicate because you cannot just delivered every neuron evenly.
Emil D. Kakkis: So it's going to be a lot trickier to deal with this on a gene therapy basis than an ASO basis. Because with the ASO, we enable the gene to be expressed, but we don't force it to be expressed. It allows endogenous regulatory mechanisms then to even out the amount of this EB3A protein. So this may be a little bit of scientific detail, but what I'm saying to you, there is a very strong basis for why this is gonna allow you to get more neurons active and allow them to be regulated properly.
And you can't have variations of expression of this thing there too too high so it's gonna be a trickier to deal with us on a gene therapy basis, then in a ASO basis, because with us. So we enabled a gene to be expressed but we don't force it to be expressed it allows an endogenous regulatory mechanism to even out the amount of this E b.
Free protein.
So maybe a little bit scientific detail, but what I'm, saying to you. There's a very strong basis for why this is going to allow you to get more new Orleans active and allow them to be regulated properly.
Emil D. Kakkis: And I think that's why we believe ASO was the best method among those. And among the ASO methods, we have the best targeted region, and that's our confidence in what we're doing. At the same time, we're gonna run fast.
And I think that's why we believe day. So it was the best method among those and among the S. L methods, we have the best targeted region and that's our confidence in what we're doing the same time, we're going to run fast.
Joon So Lee: Thank you.
Yeah. Thank you.
Your next question comes from the line of he got natural opiates from Citigroup. Your line is open.
Yigal Dov Nochomovitz: Your next question comes from the line of Yigal Nochomovitz from Citigroup. Your line is open. Hi, great. Hi, Emil and Tim.
Hi, Greg Hi, Emil and team. Thank you for taking the questions. So could you provide a bit of perspective on ultrasonic strategy to differentiate <unk> profile from Roma Susan gives them as you know both antibodies targets for Austin and in light of the fact that Amgen is also pursuing osteogenesis imperfecta.
Yigal Dov Nochomovitz: Thank you for taking the questions. Could you provide a bit of perspective on Ultragenyx's strategy to differentiate citruzumab's profile from romasuzumab given, as you know, both antibodies target sclerostin and in light of the fact that Amgen is also pursuing osteogenesis imperfecta with Romo in a phase one trial that was recently posted on ClinTrials? And then secondarily, if you could comment on the advantages of targeting sclerostin as opposed to RANK-L or TGF-beta for osteogenesis imperfecta given, as you know, that Amgen is pursuing OI phase three and OI with Prolia, and Sanofi is pursuing OI with Fresolimumab in phase one.
With Roma and a phase one that was recently posted on from trials and then secondarily. If you could comment on the advantages of targeting square roston as opposed to rank al or TGF beta for osteogenesis imperfecta, given as you know the Amgen is pursuing oh.
<unk> phase III NOI.
With Prolia and Sanofi is pursuing a oi with fresh lemon mab in phase one.
Emil D. Kakkis: Thanks.
Emil D. Kakkis: Good, thank you. This sounds like another variation of target on our back questions, but so Look, we're very familiar with Romo, and in fact, Michael Minsky, that works with us, worked for Amgen for 10 years on Romo and has a lot of knowledge. It's a good anti-sclerosin antibody. However, its main commercial potential for Amgen has been around osteoporosis. As part of their development program, they are required to do a pediatric investigational plan for Europe, which requires them to run a study, so they are running a study. What they will do with that in the long run is unclear, but the idea, the tip is that they just have to try to test their product in that population, but they're not focused on that population.
Good. Thank you is it sounds like another variation of target on our back questions, but so.
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Look we were very familiar with Romo and in fact, Michael Minsky that works for US worked for Amgen for 10 years on Romo and has a lot of knowledge. It's a good anti school as an antibody it's main commercial.
Potential for Amgen has been around osteoporosis.
As part of their development program. There are required to do a pediatric investigational plan for Europe, which requires them to run. The study. So they are running a study what they will do with that in the long run it's unclear, but the idea that the Pip is just they have to try to test their products in that population, but they're not focused on that population.
We're going to look at the dosing and dose regimen uniquely to apply to OI, and we think the dosing may need to be higher, and it's in pediatrics, and they're doing therapy for one year, whereas I think we will need to do it more chronically or have at least an induction in a maintenance phase, which is not part of their program. Our focus on OI will allow us to adapt the dosing and regimen to optimize for the OI indication.
We're going to look at the dosing and dose regimen.
Uniquely to apply to O I.
And we think that dosing may need to be higher and it's in pediatrics and.
They're they're doing therapy for one year, whereas I think we will need to do more chronic for have at least the induction in the maintenance maintenance phase, which is not part of their program.
So our focus on a while I will allow us to adapt the dosing regimen to optimize for the O Y indication that said.
Yes, we will still have to deal with it but.
Yes, we will. We'll still have to deal with it. But OI has a lot of patients and a lot of different types that can benefit. And we think somewhere in there with the dosing and other issues that there's a very important product that
Is a lot of patients and a lot of different types of it can be benefited and we think somewhere in there with the dosing and other issues that there's a very important product.