Q1 2021 Dicerna Pharmaceuticals Inc Earnings Call
[music].
Okay.
Good afternoon, ladies and gentlemen, and welcome to the di share now Pharmaceuticals first quarter 2021 earnings conference call. As a reminder, this conference call is being recorded at the company's request I'll now turn the call over to your host will Graham Inc of Stern IR. Please go ahead.
Ed.
Thank you operator, good afternoon, everyone and thank you for joining US to review day survives first quarter 2021 financial results and operational highlights for anyone who hasn't yet had a chance to review our results. When you issued a press release after the close of trading today, which is available under the investors <unk> media tab on our website at <unk> Dot com.
You May also listen to this conference call via webcast on our website, which will be archived beginning approximately two hours. After this call is completed.
Speaking on today's call will be turned as president and Chief Executive Officer, Doug Fambrough, who will review our program portfolio and strategy and Chief Medical Officer, Sriram, Maraud Yang who will discuss progress in our key programs and Chief Financial Officer, Doug Pagan, who will review our first quarter financials. We also have Jim Weissman our true.
Operating officer, Rob <unk>, our Chief commercial officer, and Bob Brown, our Chief Scientific officer available today to address your questions during the Q&A session.
During our remarks, we will open the line for your questions.
I'd like to remind listeners that management may make forward looking statements on today's call pertaining to the company's financing business and operations, including the discovery development and commercialization of our product candidates and technology platform and the therapeutic potential thereof, and the success of our collaboration and any potential future collaborations.
Such forward looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements.
Applicable risks and uncertainties include those relating to our preclinical research and clinical progress and other risks identified under the heading risk factors included in our most recent form 10-Q and form 10-K, while we may elect to update these forward looking statements at some point in the future. We specifically disclaim any obligation to do so if our views change.
Now I'd like to turn the call over to Doug Fambrough, <unk>, President and CEO Doug.
Thank you good afternoon, everyone and thank you for joining us.
<unk> entered 2021 with momentum and the financial strength to continue to build on that momentum. There are currently four day stern of galaxy molecules in clinical development the dose for all known type primary hyperoxaluria.
H they'll set the rent per alpha one antitrypsin deficiency associated liver disease, Archie 6346 for chronic HBV with Roche.
In AMG P. T L. Three targeted program under our Lilly collaboration the clinical programs for growth to six in the coming months with our D C or D alcohol use disorder program and another Lilly cardio metabolic program targeting LTA that we anticipate to enter the clinic.
Shortly.
Beyond those six there are currently five more galaxy molecules with declared clinical candidates in preclinical development, which includes a new development program in 2021 under our Novo collaborations.
And behind this 11 strong development portfolio of more than 20 research stage programs, many utilizing our galaxy plus technology that extends delivery to tissues beyond the liver.
Some of these discovery programs will advance the formal development later this year, including the startup of proprietary programs utilizing galaxy plus.
We had the resources to drive this pipeline forward, we started the year with approximately $570 million in cash cash equivalents and marketable securities and since then we've received more than $230 million and collaboration milestone payments, including the milestone payment from Roche for the phase III.
Start of Archie 6346 in chronic HBV as well as from the sale of our royalty interest in a peer company marketed program.
We anticipate receiving additional cash this year and are hoping to achieve net zero cash burn in 2021, while fully funding our development program and preparing for a commercial potential commercial launch in 'twenty 'twenty two of those are in the program to treat all loan types of primary hyperoxaluria.
That is currently in pivotal clinical development.
Regarding the dose around we are on track to read out top line results of the <unk> two pivotal trial mid year as a reminder, <unk> two is enrolling subjects with ph type one and ph type two and the data is positive as expected should support full approval for both of those.
Ph types.
We are also currently enrolling a trial for subjects with ph type three called class for <unk>.
COVID-19 spikes impacted the enrollment timeline, but we believe it will be fully enrolled in the very near future.
We intend to include ph type three data in our planned NDA that will push that NDA submission into the fourth quarter and any of them.
We fully expect that those rent to be our first marketed product and thus mark our transition to a fully integrated biopharmaceutical company as we intend to market that dose in the United States.
P. H is an ultra orphan indication so it's ideally suited for the initial build out of our U S commercial organization, which is already well underway, including with the recent hire of our vice president of sales.
We expect to build further from there next for the orphan <unk> liver disease market and with larger specialty call point and non orphan indications beyond that does that this development portfolio supports a logical step wise increase in U S commercial capabilities within the dose as the point of this.
Peter.
Our maturing and growing development portfolio is we believe more likely to enjoy clinical success than the average success rates for our industry.
Some of that comes from the unique constellation of properties shared by our Galaxy molecules and we also think likely shared by our galaxy plus molecules.
These include high Tolerability lack of off target effects long duration of effect simple administration regimens.
And relative to some programs tissue specificity.
For our own portfolio, we focused on diseases with clear disease mechanisms that we can directly impact with RNA eye such.
Such as with the primary Hyperoxaluria.
Per one any trips and chronic HBV programs in other cases, we followed genetic association that implied likely success for our treatment mechanism such as with the alcohol use disorder program and several of the collaboration program.
In certain cases, where development risk is higher such as in achieving functional cure in chronic HBV and with more novel cardio metabolic targets.
We've entered into collaborations structures, where the cost and clinical proof of concept risk is taken by our collaborator with <unk>, having the right to opt back in to co fund development and co commercialized. After a clinical proof of concept has been achieved I'm, referring there to a roche and novo collaborations.
There's a well from which we can draw new programs as deep.
As we presented during the first quarter and last year, our Galaxy plus technology is achieving strong and specific gene knockdown in multiple non liver tissues, including various CNS cell type muscle adipose tissue and tumor associated immune cells and as yet undisclosed work from our research labs.
Extends further than that.
We may become a little more adventurous in our target selection going forward pursuing intriguing mechanism and major opportunities enabled by galaxy, plus and particularly suited to arent AI in contrast to traditional modalities and to other genetically based mechanisms such as gene therapy or gene and base editing.
I look forward to talking about those programs and future update as building our proprietary pipeline as a high priority in.
In addition, we anticipate additional discovery collaborations although that is not our focus for 2021.
So as you should see from our portfolio of current programs, our deep opportunity set for new programs, our risk, reducing and revenue generating collaborations current financial resources and our plans move to commercialization of the dose or at next year. We are confident that we have paved the way for <unk>.
Strong value growth that can continue for many years at an attractive risk profile.
With that general overview of our strategy and the means to execute it.
I'm now going to turn the call over to our EVP and Chief Medical Officer, Sriram <unk>, who.
Who will give an update on our core development programs Shri.
Thank you very much Doug and good afternoon, everyone.
As Doug mentioned, we continue to make great progress across our clinical development programs and as of now we have 10 clinical trials underway or expected to begin in the near term evaluating our four pipeline candidates.
<unk> for primary Hyperoxaluria <unk> for Alpha one antitrypsin associated liver disease, RG 6346 for chronic hepatitis b viral infection with Roche and <unk> for alcohol use disorder.
Let me begin with an update on the das around our most advanced program, which is in development for the treatment of primary hyperoxaluria.
Primary hyperoxaluria or ph is a family of ultra rare genetic disorders, causing hepatic oxalate over production that could result in a life threatening kidney damage as well as damage to other organs.
Jordan and impact of disease continue to become clear in ph ILD and ph three as newer data emerge demonstrating the need for a treatment that can address all known Pete subtypes.
We are developing our galaxy RNA <unk> product candidate for the treatment of all of the known subtypes ph one ph two and ph. Three there are currently no therapeutic options available that treat all three known forms of ph.
Having completed enrollment despite the ongoing pandemic surge late last year I am pleased to say that folks to our six month double blind randomized placebo controlled pivotal trial in patients with ph. One ph two who are older than six years of age is nearing completion with the last patient last visit expected to take place.
This quarter.
As a reminder, the primary endpoint of this six month study is the percentage change from baseline in the urinary oxalate based on the area under the curve of 24 hour urinary oxalate excretion between days 90 and $1 80.
We anticipate announcing top line data mid year as we also prepare for an NDA submission based on this study.
In addition to <unk>, we continue to enroll our <unk> for single dose trials ultimate offs around in patients with ph free although enrollment has been slower than expected due to the current COVID-19 environment.
This study is designed to evaluate safety tolerability and PK PD of Ddos around in patients with ph <unk> with the additional objective to evaluate reduction in urinary oxalate as a secondary endpoint for efficacy or.
Our plan is to include data from this trial in our NDA submission to support a potential approval in ph three.
Our expectation is still have top line data from <unk> four in the third quarter setting us up for a submission of them. It also had the NDA in the fourth quarter of this year.
Moving on to additional industrial on trials early in the second quarter, we initiated patient dosing in five seven are open labeled study open with us around in patients with ph, one ph, two who have severe renal impairment, including those on dialysis.
Our <unk> eight open label trial in patients from infancy. After six years of age with ph. One ph. Two is also expected to initiate this quarter.
Both of these studies are expected to complete after we have submitted the first NDA and we therefore plan to submit these data as supplemental filings subject to that also has approval to support label expansion for treatment of these patient populations.
Next is our investigational Galaxy candidate RG 6346 for the treatment of chronic hepatitis B virus infection, which is in development in collaboration with Roche.
The disease affecting an estimated 300 million people worldwide and contributing to the death of more than 880000 people. Each year. There is a tremendous need for a treatment that could result in a functional cure for this disease.
During the first quarter, we were very pleased to announce that Roche had initiated RG 64 six.
A phase II platform trial.
We will evaluate the efficacy and safety of RG 6346 in combination with multiple additional agents with different mechanisms of action.
This platform trial design allows comparisons of multiple combination therapies against a common control arm as well as the introduction of additional treatment arms at later time points.
Gross added <unk> 64, 6% of the trial in March as part of new treatment arms in combination with standard of care nucleotide therapy, and then triple combinations with the Pegylated interferon Alpha <unk> Roche's core protein allosteric modulators defined inhibitor or roche's novel Investigational <unk> seven agonist.
This trial is being conducted entirely by Roche and will evaluate the percentage of participants with hepatitis b surface antigen loss.
At 24 weeks after the end of the 48 week treatment period as the primary endpoint.
The phase one trial of <unk> 346 that we initiated and for which we are responsible continues in parallel with dosing cohorts that include follow up durations of up to $48 72 weeks.
The positive interim phase one results that we presented last year showing that four monthly doses of <unk> hundred six treatment resulted in substantial and durable reductions in hepatitis b surface antigen levels lasting up to one year. Following the last dose will indeed, very encouraging and we are optimistic about <unk>.
<unk> potential as part of a functional cure combination treatment regimen for chronic HBV.
Turning to Bill Tessera, we continue to advance our clinical development program for the treatment of Alpha one antitrypsin deficiency associated liver disease or <unk> other.
Other than liver transplantation, no treatments exist for APLP, a disease caused by the production of abnormal.
Protein by the Z allele of the surface a one gene that can result in chronic liver disease, leading to fibrosis cirrhosis liver failure or cancer.
Individuals with two copies of the <unk> are believed to be at increased risk of developing a PLD.
Our rare disease recent epidemiology research indicates that approximately 120000 individuals in Europe and 63000 individuals in the U S. Dairy this disease the genotype.
It's estimated that 10% or more of these individuals may have a TLD and recent research suggests that <unk> is both under recognized and under diagnosed.
Our phase one multi cohort single ascending dose trial.
The safety Tolerability and PK PD of built SRM and healthy volunteers continues.
We recently completed dosing in our fourth dose cohort and a fifth dose cohort is now under way we.
We anticipate reporting top line interim data from the first four dosing cohorts at midyear and are targeting presentation of more complete data from the phase one trial at a scientific conference later this year.
I'm also pleased to report that we have initiated patient screening for our multiple dose randomized placebo controlled double blind phase II trial named as trailer.
Which will evaluate the safety tolerability and PK PD or <unk> in adult patients with <unk>, who have the PIV genotype.
Our teams continue to work hard protract the impact of the COVID-19, pandemic I'm not trying to rollout and based on present projections, we anticipate dosing the first eligible patients in the coming months with the majority of worldwide sites are expected to be active.
Turning to the latest addition to our core pipeline on our last quarterly call. We revealed our next Galaxy clinical development candidate <unk> for the treatment of alcohol use disorder.
Alcohol use disorder or <unk> is a chronic disorder that is associated with a range of medical psychological personal social and economic problems.
<unk> and approximately $250 billion in annual medical economic and social costs, and representing an area of substantial unmet need.
About 14 million adults in the U S experienced <unk> and few others, 10% seek treatment.
Fewer still roughly 140000 people in the United States actually receive pharmacotherapy for this disorder.
While there are a variety of factors contributing to the low adoption of pharmacological therapies for <unk>.
We think there is significant opportunity for a safe targeted easy to use therapy that can be combined with behavioral interventions to help individuals with <unk> meet their treatment goals.
<unk> is our investigational <unk> therapeutic designed to deliver a liver specific knockdown of aldehyde dehydrogenase, two or <unk>.
<unk> is a key liver enzyme involved in the metabolic breakdown pathway of alcohol.
In March we provided an in depth discussion of our <unk> program that included a deep dive into the LDH to target rationale and detail on the limitations within the existing treatment landscape shared biotherapeutic expert Dr. Henry <unk> flow from the University of Pennsylvania's Perelman school of Medicine.
A replay of the webinar remains available on our website for anyone who missed it so I won't delve into great detail today, but standard briefly <unk> mechanism is designed to result in an intolerance of alcohol in moderate amounts providing real time physiological feedback that can assist individuals to avoid harmful levels of alcohol.
Intake.
We believe that <unk> expected long duration of action with easy subcutaneous dosing and high target specific city with minimal to no side effects similar to what we have observed with our other galaxy molecules together present, a compelling potential profile.
We are very enthusiastic about the share of <unk> prospects as a potentially game changing therapy for people with <unk> and are looking forward to taking it into the clinic.
We are on track to file our IND for <unk> mid year and plan to initiate the phase one trial in healthy volunteers soon after in the third quarter.
The phase one trial will include an assessment of low dose alcohol interactions, who confirmed the pharmacodynamics safety in the target profile consistent with preclinical models of liver specific <unk> knockdown.
As we approach mid year I am pleased to say that from a clinical development standpoint, we are making steady progress towards multiple study starts and data readout milestones over the remainder of 2021. In addition to the significant deliverable of preparing to submit our first NDA and important and exciting milestone for the company we look.
Forward to an eventful balance of the year.
I'd now like to turn the call to debt to EBITDA.
To review our financial results Doug.
Thank you Sri.
I'd like to briefly walk through the key financial results for the first quarter 2021, and direct you to our press release outlining these results and our form 10-Q, both issued after close today.
Net loss for the first quarter of 2021 was $30 million or <unk> 39 per share compared to $22 5 million or <unk> 31 per share for the same period last year.
<unk> for the first quarter of 2021 total of $47 6 million.
Impaired to $34 million in the same period last year.
The year over year increase in revenue was primarily attributable to an increase in services performed under the Roche Alexia on and Novo collaboration agreement.
As of March 31, 2021, we had approximately $138 million.
Current deferred revenue, which we expect to be recognized over the next 12 months and approximately $318 3 million of non current deferred revenue expected to be recognized over the following several years.
R&D expense for the first quarter total of $56 million compared.
Compared to $43 2 million in the same period last year the year over year increase was primarily driven by an increase in employee related expenses as a result of higher R&D head count necessary to support our expanding pipeline and collaboration agreement.
As well as development costs associated within the dose range clinical development program.
G&A expense for the first quarter of 2021 totaled $27 million compared to $16 million in the same period last year.
Year over year increase was primarily driven by employee related expense as we increased head count to support our growing operation.
As well as increased professional services.
We expect our operating expenses to increase in the coming quarters as we continue to grow head count to accommodate additional R&D activity and launch readiness as well as from higher external spend associated with increased activities in our pipeline.
During the first quarter of 2021, we received $32 $9 million in milestone and reimbursement payment from our collaboration partners.
We continue to guide to receiving over $83 million for the full year of 2021.
These payments represent an important source of proceeds and demonstrate the value. These collaboration program should continue to generate as they mature.
As of March 31, 2021, we had $544 $9 million in cash cash equivalents and held to held to maturity investments.
Impaired to 56, sorry.
$568 $8 million as of December 31, 2020.
In early April we announced the sale of our <unk> royalty interest to royalty pharma for an upfront amount $180 million with the potential to receive up to an additional $60 million contingent.
Contingent on sales based milestone this.
This non dilutive transaction extends our cash runway into 2024.
This transaction will begin to be recognized in our financial statements during Q2.
We also anticipate signing an O U S commercialization partnership from the dose range this year.
Our goal has been to maintain a strong balance sheet through the planned NDA submission for new dosing in the fourth quarter and potential 2020 to commercial launch.
That concludes my review of the financials I would now like to open the call for questions operator.
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.
First question comes from the line of Jonathan Miller from Evercore Your line.
Hey, guys. Thanks, so much for taking my questions and congrats on all the broad progress. It seems like you've done a lot of work this year and there's a lot of stuff coming to the clinic.
I'd like to start on ph since that's the most near term stuff I guess can you talk a little bit more about your choice to delay filing to wait for the ph type three data.
Versus going forward with ph type, one and two and then moving on within F&B when <unk> is ready.
And secondly, now that you've had some time enrolling ph three patients can you give any more color on that market, how readily identifiable with patients or how many are seeking treatment as we start to think about ph type three becoming a commercial opportunity.
Secondly.
Yeah, what can we expect from the initial data from <unk> releases I know, it's healthy volunteers and I assume we'll see Thailand thing data, but is there any other meaningful information we can get.
Safety or details of lung surveillance that is going to be important day in evaluating those initial releases.
Yeah.
Hi, Don put a lot on the plate there, but we'll bank through Ed Sri will talk about our filing strategy and then Ross Chapman.
I'll chime in on the ph three market then what's our day one right. So so John as you know I mean, the primary value proposition from the dos around that we see is the fact that we have the potential to treat all three types of ph. That's been our incoming strategy. We've had agreement on ph, one and two with the FDA with ph three.
There's still some conversations going on but we believe that the delay that we're seeing in enrollment is not of a degree that.
Warrants are wanting to split the fab, we think that we expect the enrollment to complete.
Imminently and.
With that we are able to stay on track for our plan, which is an integrated file that includes data on all three types of patients.
With the goal to get approval for ph, one and two.
And pending the data from phase III, but so at this point, we're staying on track with our.
Our original plan.
Growth.
Thanks Jade.
John I appreciate the question in terms of the free market and I wanted to start with we're starting to see some additional data being published through off of the Europe around the burden of disease ph III. So this is where we're starting to get into.
What could be the market here and we're seeing that.
<unk> three patients who are suffering from current kidney stones.
And impaired renal function.
We're starting to quantify that.
And what we've heard from our scientific advisors is that there are a group of these patients that are demonstrating.
Awesome.
How many I think we're still being very conservative in our estimate.
And in terms of what we're looking at right now we're thinking that based on what we know today.
But frankly, even over the last few quarters that keeps changing about 20% of those patients may be demonstrating symptom.
We certainly when we have diagnosed.
They will need to have a genetic tests confirmed <unk> three and we're continuing to size up the market that way.
Alright, sorry, do you want to talk about day, one <unk> data.
Yes, John.
John went so fast I missed the.
Any question he was asking about what to expect in the initial release, obviously, we'll talk.
Top line on the suppression of the protein and that's healthy volunteer trial do you think we're learning from safety.
We will provide information John on the overall safety profile, we have been monitoring safety and we will we will report the safety and Tolerability of the data up to that point.
And I think what Youll see is the data we have that gave us the confidence to proceed with our plans for phase two.
<unk> selected a dose and a dosing regimen to move forward.
Line data Youll see some parts of it and then later in the year the more complete information.
Does that answer your question, Yes, certainly we would not expect to see declines in lung function in healthy volunteer population.
Thanks, John.
Great. Thanks very much.
Right.
Next one on acute and many through Haar from SBB Leerink Your line.
And proceed to liver transplant at which point they would no longer frankly, no longer have meaningful ph because deliver the source of the oscillator I'm not sure we have any specific numbers to quantify those to be rough Jack moving.
A little bit of a crack at it and record we're trying to do a segment of the market I think we've talked to him previous call about the house in the data is across the range treats for th, one two and free and dug spot on we're seeing th.
Ph patient.
Demonstrate and demonstrates their disease and decent dramatic across all of the branches frankly, the easiest one to <unk> or.
Or the Internet.
But what we frankly theme in the box studies and entertaining patients. We have as you would expect in any ultra rare disease.
Number of silent sufferers out there and we're still really trying to pinpoint down different segmentation each of the three.
But this time.
Now with respect to your second question on timing of clinical trial data from partners and specifically the Lily and three and LTA. We currently don't know the timing or the day to release plans up literally we will be sure that when we do understand it.
Thanks correct.
Credit to take your questions.
Uh-huh next question comes from the line of Maidu Kumar from Goldman Sachs, you're in our lives.
Hey, guys, Rob on here from Ado, Congrats on all the progress I just have two quick questions first what do you think are the key metrics by wishing that goes around can differentiate from approved garden AI drugs and ph one and then additionally, what have you learned from pier.
If one any tricks and orange I drugs about clinical endpoints to examine from Belfast Saran and.
And then now initiated phase two trial.
Well I'll take a crack at your first of all in the three can address the bell system endpoints question.
Clearly key differentiation for that those around from the Lucerne molecule is our ability to dose we hope all the th types ph type one type two and type three as well aware ph type two and type.
<unk> are not addressed by luminous Sarah within Th, one where there is patient overlap. We are optimistic based on the study buyouts three open label study, which has the same dosing regimen is the fax two pivotal trial.
Based on that fact, three data we are optimistic that we may report a higher level of normalization of oxalate levels, which we view as the most important metric.
Looking at the disease.
It is important to note that.
Oxalate is in the normal zone.
Then you have effectively normalized the disease day for the patient and even disease management activities you have the potential to stop doing those with elevated levels of Oxley don't think that's something that's going to occur. So the larger the fraction of patients who achieved a stable normally.
Asian level, I think is going to be viewed as a differentiating factor and we are optimistic that we may achieve that line.
Proceed with the box to data is related to that is the average oxalate level achieved by patient Similarly.
More reduction no better.
So the absolute level achieved in the percent normalization. We think is very important beyond that we are.
Have received a lot of positive feedback about the regiment of our product and its presentation as a pre filled syringe for self administration. This is a lifetime chronic disorder and that sets up an extremely convenient no health care practitioner acquired.
To remember dosing regimen with a small volume small needle so administration subcutaneous injection that we believe may emerge as a preferred format for.
And this disease for dosing at Rmi therapy. So there are a number of differentiation channel that are possible and in the case of the dosing format that is.
We're confident we're on track to launch with the Springfield, So rich.
South restaurant, so so the therapeutic hypothesis for both of US are as you know is that by reducing by knocking down the expression of the gene and deliver you reduce the abnormal protein and deliver that allows delivered to regenerate. So our face to study is designed wanted to confirm that we are able to knock down.
A liberal protein, which we fully expected to do based on the mechanism of action.
We then expect to see that as a result of the M. A decrease in the day abnormal in the levels of abnormal AIDS and deliver.
We have histological endpoints based on biopsy associated biopsies them with a cohort both a six month as of 12 months duration of our face to study that will evaluate improvements in histology, where we will be looking for reductions in globules as well as disease activity.
As well as looking at fibrosis, we have complimented that with the use of imaging studies that will allow us to assess total delivered if you will.
Behavior for the lack of a better word in terms of stiffness using by Bush Campbell anymore, Elastography and combine that with soluble biomarkers.
To that end the recent.
Press release from Arrowhead based on five patients worth of data demonstrating some improvements in fibrosis patent consistent changes in many of these markers is actually a very encouraging sign yes, it's small numbers of patients its own data, but at 12 months seeing some changes in.
And the app's, although in the absence of a placebo controlled gives us encouragement that our plans are well club true and we are planning on collecting all of that information in the face to study.
Then inform us for our regulatory directions to decide what will be the basis of approval interface <unk> study.
Even indication, where the diseases really ed enough, where traditional liver outcomes and the long term, we're going to be difficult to follow up so.
So so I think I'm very encouraged by the recent data that quite compatible with the plans. We have made we're excited that we've designed to study at his two cohorts looking at six and 12 months of frequent we've included a population that covers is true true at four so.
Now the focus is on getting a growth.
<unk>.
All right. Thanks Ross.
Next question comes from vinyl Tiffin relief from stifle you're no line.
Hi, This is Bonnie quite John fifties, Thanks for taking my questions for a ph three is there any color that you can provide on how you plan to find these PSP patients, especially since there as you described on this island suffers.
And also is there any overlap it through the th three diagnosing physicians and the ones that also diagnose and treat two patients.
Yes on the highest drop thanks from the question and related to the page through marketing and we're already patient.
So one of the key aspect book from a health care professional five and from a patient standpoint effect will be education, and you can start to see some of that already on our website and working with.
The patient advocacy groups strength.
So awareness of the disease and the symptomatology.
Key aspect.
That we have to get out into the marketplace around if you have frequent stone.
You really need to talk to your doctors are walking knee deep doing those types of concepts need to really continue to.
Get embedded into the marketplace in terms of education also in terms of the appropriate in differential diagnosis. The typical ph station.
Three to five year patient journey seeking a differential diagnosis and you've got to really good tools right at our fingertips urinary off to a half day and genetic testing. Thanks turnover I'll have a program to help I'll share professional differentially diagnose th.
And I think having access to accompany.
Virginia Tech is yet another way to take a barrier off the table. So that physician can be informed in the panel that we're designing will be a panel that not just book the th. Thank you the physician information that goes beyond th because frankly average every patient.
Physicians are Thanksgiving necessarily a ph patient and part of what we're trying to use and help these patients get through a differential diagnosis.
Okay and the band pocket the physician the population. This national group is the same line. So yeah. So the same groups of urology from the projects who were.
Statement.
And my last question is I was wondering what are your thoughts regarding on islands Mason eliminate abdominal all data and what can you believe before and then that day.
Thank you.
But I think you're referring to the network Calcinosis data Bonnie and so so so we were encouraged to see the day that you want. Another example of what the potential impact of.
Durable reductions in the early oxalate overtime, Kevin cheap now.
Customers as a measure of ultrasound, we're looking at it to our program.
Is initially focused on demonstrating a durable and meaningful normalization of urinary oxalate in a large proportion of the subject.
But we see then that broke out from US. This information that's again emerging evidence.
In our case, we're measuring it in our products to program is all of our parks free studies.
It will take time to have that data, but for me again for the validation.
In hyperoxemia areas lowering auction leave loads and reducing currently actually.
A good start.
Okay. Thank you so much.
Next question comes from the line of yarn Werber from COVID-19, you're no line.
Hi, everyone. Congrats to the team. Thank you very much for taking my questions is Brandon on through your first I know you touched on milestone payments, but can you just come from one more time, what you expect maybe in terms of cadence, which milestones you're thinking maybe the rest of this year and in the next year. If you can.
And then just really quickly as your as you're looking ahead to new program extended CNS, maybe kind of gives us a sense, how you're prioritizing different targets that you think are especially a minimal or an AI versus maybe other modality and if you think you took to partner that program for development. Thanks.
Does per guy that's going to take them off that question. Thanks for the question, Brian Yes. So the milestones what we've laid out is hurting last year at the end of the quarter. We've made out of five quarter hundred million dollars paid we.
We recognized 17 Q for now and that recognize that received and now 30 32 nine this quarter. So the remaining amount there remaining 50 year or so will come in unevenly milestone payments range from.
Small reimbursement two large milestone from $10 million, but they'll come in over the next two quarters relatively evenly we haven't forecaster, giving guidance on next year because some of these milestones are dependent on the ones preceding them. So we'll look to give more guidance as we get towards the end of this year.
Thanks, Doug with respect to the target prioritization quick questions such an interesting area I mean, specifically for the CNS as you know we have a collaboration with Lily and it has been a close collaboration an urgent generation in pain space. There is potential which I think you alluded to for us.
To do certain orphan indications on our own there is a dialogue with Lily with respect to some orphan indication.
I would note this unit is pretty crowded space.
Where there has been a number of companies focusing with a number of different modality and as we evaluate more broadly indications to go after with the Galaxy plus technology.
We're not that just thinking about CNS I think amongst the set where.
Pretty deep in.
Cns's the minority.
We expect.
To be advancing.
Multiple programs proprietary purpose not necessarily orphan out of galaxy, plus internally and there may be a neuro program amongst them that there will be non euro as well.
Each indication is its own little universe of detail in fact, so it's hard to make general statements about what makes a or an AI indication.
Make what makes aren't AI preferable in general relative to others, but.
The modality, but in some cases it has to do with the fact that the targets not very drug a bowl in other cases, it has to do with the long duration of effect in the area under the curve or difficulty with multiple administration, which we avoid with the long effect with our Nai. So there are <unk>.
He's of of.
Reasons, why aren't AI would be preferable.
They are different if you're thinking about G would you would you use Christopher against this target compared to which use the small molecule against the Chinese so I'm not sure. There is a general answer there. However, we do think about that set of potential competitors for different technologies as part of our review of an indication there are a bunch.
Of other things that go in the strength of the therapeutic hypothesis, the predictability of the animal models the difficulty in length of the clinical trial programs.
Including endpoints selection and things like that so it's really.
As soon as the three dimensional chess game choosing these indications and we're trying to be very careful about it but it's harder are described general rules.
Alright, great. Thanks very much.
Next question comes from the line of Luka, you see from RBC capital you are in all line.
Oh fantastic. Thanks, so much for taking my question Congrats on the progress maybe the first one a P. H I think we've seen the masked Iran actually off a pretty good commercial start to your particular ask you ask so wondering if that impacts at any sore from our shape your ongoing dialogue with a potential partner here and maybe a bigger picture how should we think about timelines per potential partnerships X.
For the dose rats, and then M. P. H three per record it correctly fireworks for his enrolling just six patients I think total including placebo. So can you just to remind us what gives you confidence that such a small data said would be sufficient to get a label that actually includes ph three as well. Thanks so much.
Rob you want to address Loma, Sarah lunch share.
Thanks, Doug Bank, we're going from the question in terms of the.
Buena sarin any inquiries from our partners and the bottom line has been our own car.
Conversation proceeded quite isolated with our expectation.
<unk>.
There are from from our discussions with partners has been really interesting they're looking at the home market not just the th one market and what they see is.
Hi, unmet need from promising results as we talk from the are cooler data from here.
Back to where I was talking earlier was a you've got a high burn the receive an <unk> an emerging in emerging burden of disease and pieces for your basement.
Partner attached partners that we're talking about understand that.
And they see the potential with the new dose, earning five package and being able to bring that package for.
You you Asia and other market.
And they just see a lot of potential outside here for the program and we're really optimistic and wrapping up those conversations and getting a deal done.
Look at the history as far as the use of the box for data towards a potential ph three submission on approval.
I think behind your question is the indication of course, we have more content. We have agreement on VH, one NPH to the way we think about ph. Please as follows.
<unk> the disease that it also characterized by access obsolete production.
Disease for which increasing implications of that disease state are becoming apparent. It's the most basically described formal so that information was a little bit less than what was available for ph went into she'll be now have that information available to us.
Five four is going to be a single dose study that is double blind placebo controlled and in which they're going to assess safety dollar booty PK PD, but also Ah respondent analysis, where <unk>.
30 percentage reduction in the early oxalate from two consecutive visits which is known to be a threshold that is clinically meaningful it's confused by nephrologist in clinical practice and if we convincingly show that.
Then we expect to make the argument that.
We are lowering you are they actually them. This disease, we know what the importance of oxalate is and given the disease burden do we have an opportunity in the context of the overall ph one PX two data sets and looking a free findings to seek approval for all types of P. H I.
I should say that of course, the PHC part of this.
Is less agreed to the FDA them RPX free plans, but our confidence is all going to be primarily dependent upon the data that comes in but.
But that's going to be our strategy.
Got it incredibly helpful. Thanks, so much guys.
Excellent on queue is golf local moving from Citigroup you in our lives.
Alright. Thank you very much for taking the questions that I had three first on off by X seven am I correct that you are going to be measuring Egfr and you can expect the dose and to have an impact on egfr slope and these patients, giving a reduction in oxalate and perhaps even potential delay dialysis and the second question.
<unk> will follow up on a previous line just wondering what are you hoping to see in the phase two data for Alpha one antitrypsin deficiency that will meet your objectives target product profile for both since around and then finally dog I think you mentioned at one point in your prepared remarks, and you'll be coming up.
Becoming a bit more adventurous with respect to future indications Park Galaxy program platform. So I was just wondering if you could provide any preview Naomi.
When you May go beyond the latest game programming alcohol use disorder and king.
Sure. So three we'll start off on the 575.
Five seven is actually the study in which we will evaluate the ability over the dos around to reduce hepatic obstinately production.
In people, who have a degree of needles insufficiency, including being on dialysis that prevented urinary obsolete from being the right markers. So we will use plasma oxalate reduction.
Evidence of efficacy.
<unk> is about demonstrating the efficacy open is also revenue population that we have not yet studied so it's not a population of which we will then be evaluating whether progression of <unk> of GFR reductions and we go onto the new dialysis, so things like that it's actually if I am moving effects from obviously.
Okay got it.
So that was 11 the second your second question was about.
And what we expect to see in phase two.
And I will repeat my prior answer which is that the goals of the face to study or to demonstrate the ability of the selected those regimen.
To reduce alcohol and abnormal AWP levels and deliver.
The primary endpoint is actually at on the standard because that some ask if that's available we want to measure it when they deliver ensure that we can reduce it we're going to do the cereal boxes that will evaluate histology to see what we're doing to the abnormal globules that accumulate and deliver and other markers injury, we will be evaluating fibrosis.
We will combine that with.
Imaging measures of liver stiffness, which are an indicator of fibrosis E fibrose calm and I'm already lifestyle goofy.
And we will add soluble biomarkers that are also indicative of.
Progressive we were injury in addition.
It's a combination of a number of those things all moving in the right direction that.
That will be the basis of the day that will be the data that will collected faithful and then convert that into a proposal for a meaningful endpoint in our phase III study is the basis of approval in discussions with the regulators.
We have the expectation of observing improvement across all of almost parameters, but we're not going to get quantitative about what we're looking at book.
And can you repeat the third question.
Sure Doug I think you'd mentioned at one point that you were going to be.
Other interest of course [laughter].
There are.
[noise] Galaxy Costco with a lot of place.
And that raises a lot of possibilities for what we could do.
Aren't AI is not inherently an orphan disease or metabolic disease.
Technology.
<unk>, perhaps will impact every therapeutic area with possible exception of anti Bacterials because.
Doesn't.
It doesn't work it bacteria.
And there are certain cases, where there is famous undruggable targets that are really intriguing.
That.
True wouldn't meet the criteria of strong genetic association in the traditional association studies or.
Obviously you have.
Not not talk about genetic diseases in that in that case.
I didn't really mean something that I could go into a lot more detail on there's going to be diversity in our in our indications, we're not going for commercial synergy.
We're going for products that in each case would support doing a commercial launch even if you didn't have a commercial operation in that area.
And I really I think was just trying to express that sense of diversity, that's likely to come out.
On this book X. Thank you very much though.
Next question comes from the line of my Mum tiny from B Riley Securities here and I'll line.
Good afternoon, and thanks for taking my question and congrats on so much going on I'm, So having real gun Doug.
So maybe just see for me just quickly on file egg.
The open they will paediatric any color on the dining there I know, it's starting next quarter, but are.
Are you thinking of this could also to sneak into the MBA.
You mean since emotional so let us know so I don't expect.
Perhaps ed data to sneak into the NDA that will have to be a supplemental.
Okay got it.
And then yeah. Most of my questions I, just follow up gratification and then on the.
<unk> Sighed again I appreciate the extensive color you value provided but I was just curious that.
On the on the dose levels, if you could comment that you've tested and you've obviously looked at it against the nylon molecule.
Just trying to understand how much knockdown and.
And how much headroom per that knocked down we need to have now that you're more at least from the I don't hate data of that you know.
The liberal healing processes out won't really quickly so just curious.
Are you comfortable with the day that you've looked at in your face line and sort of.
Have a good answer day.
We've done doses and are faithful unhealthy volunteer study, they're very similar to doses that we explore identical right in HVV and then.
The dose around before that.
You know, we're talking about another indication here, where you're going to have long term chronic dosing Ed.
And you had dose and activity in aren't AI. So.
I know that the biocide tends to focus a lot on well okay. With this group got a 5% of this group got 90% moving that one's better.
Any fight the company and it doesn't matter you are going to be doing multiple doses, it's going to go down to it smacks rapidly after two doses. So I think there.
Maybe a little too much focus on that when we were evaluating the Douglas Turner molecule versus the on line of molecule. We are also considering the ease of manufacturer of the molecules who are considering the type of preclinical toxicology studies that were done and it has implications for sequencing of later studies of.
Of course, the outcome the detailed outcome of those studies. So there are a number of things that played into it.
Ability to generate sufficient knockdown.
Frankly is fairly easy and a.
Multi dose context, and so that wasn't even the even the primary.
As I said in the past both companies are very good at making these molecules and I think either one could have been selected and successfully developed it only makes sense to do one.
Based on the totality of the data we chose era.
Got it and dark on the extra emphatic programs you said.
Majority of non CNS.
I guess my question on this to be more specific on this chessboard.
When you look at indication do you you think of who.
Who might be ahead.
From our I'd be.
Less inferior kind of more enthusiasm platform standpoint, or are you looking to sort of take.
Meanwhile, goes like your day to day, you D is that how.
How are you determining what day of similar indication you are going to go or.
I would like to have.
Some things that are the first in class and what and what we're doing.
Is.
There are contexts, where an antisense ahead may be really problematic in there a context, where we think it may not be problematic.
But the competitive environment around an indication is an important element and it matters a lot if you're competitive and a large market versus competitive and ultra orphans market.
We.
Would you wanted to be straight up.
Had an ultra orphan that.
Already being addressed fairly well with a similar modality that probably not a good place to be.
Got it thanks for the color index preceding of course.
Next question comes from the line of Ed <unk> from AC being right here in our lives.
Hi, uncle out from that everyone business Thomas Oscar in a couple of questions for us.
Crusher assurance on on on our progress we're from our per programs.
Mulk partner partner.
Perhaps first question for the phase two Roche collaboration where for six three or four six <unk>.
As we understand the.
From endpoint.
Service answering reduction what.
B fresh or the.
But we can look at.
Perfect consider Vera for success, Florida 446346.
Well in the face to study the.
Question being asked is really does it look like you can achieve functional cure with these combinations.
And that means.
S engine would go to undetected bull and remain so.
Until 24 weeks, which would be the final assessment point, so you're really looking for zero.
Oh.
Okay.
And that perhaps.
Factor robust around.
You're out line.
We are approaching closer.
To the following perhaps approval from the next 12 months.
Just supposed to imagining target and your allergies in the projects.
Any thoughts on what what draws Margaret large from look like.
Yes, it's wrong I appreciate the question in terms of our commercial activities your spot where pacing them to the NDA any and.
Targeting and the FDA free who a couple of key component.
The launch planning clearly underway at this point.
I'm really pleased and Doug mentioned that we've hired.
The vice President of sales, which is the last number of my leadership team. So we have the full complement of functions representative cross commercial at this point in time and as you can imagine all the key areas actually be expecting at this point in time are under development, such as branding message half day.
<unk>.
Pricing and contracting establishing patient services acumen and skills and last but not least now starting to design and size. This down for us our expectation it will go to market with.
Full and comprehensive promotional plan and package and we will have all the postings in place to do that in the United States.
Okay got it thanks, thanks for the other.
So perhaps price.
No short one.
For our liberties from pets.
<unk> pay their time B 4469.
Second quarter.
Any milestones associated with the power.
Yes.
Okay got it.
Thank you so much for that.
Okay.
Gotcha.
Yep Yep looking forward to a very in your file for a second half this year.
Thanks Thomas.
Next question comes from the line of Robyn Curnow ask us from choice you are in our lives.
Hi, guys. So one quick line when you thought about designing your fees to trial for even a T.
Just a couple of questions I had for you I know, there's some questions around <unk>.
Biopsies, having different levels and fibrosis improvement, depending on where you biopsy and the liver how what kind of things did you take away from the arrowhead data as far as like any.
Any potential modulation to how you're going to be running the phase two trial and what other additional parameters. What do you think are the most important parameters are additional parameters that maybe you haven't spoken about yep it'll be important to determining.
How doctors view the.
Data from the clinic clinician side I was just worried about <unk>.
She's having variable result, thanks.
I think like.
The well redesign the study.
Keeping firstly, a placebo controlled faced and stuff. So that's the first thing. So we have included the control that allows us to make meaningful interpretations of the information that we will find that's number one number two knowing that the duration of effect in which you may see improvements in fibrosis.
Will the Arrowhead data became available undergoing that's early small numbers, but still.
At 12 months.
We have designed the cord that six months and 12 months right. So we're we're getting a good sense for when are we seeing that what does the trajectory of the histological improvements that we expect to see.
Traditionally biopsy do carry the list that you described which is.
Given that you're allowed to very small portion of the liberal 70, thousands of entitlement volume.
Things get difficult to interpret but I think that the goal is to make sure that we have had a control on there making sure that we are thinking carefully about standardizing. The we live on a look at the biopsy. So simple pathologist, having predefined criteria airport, how the tissue will be evaluated so there's a series of steps that are taken in this context.
That there are a lot of learning from the last literature.
How you need to do this to get it right.
And you will certainly be thinking about it.
But in order to overall interpret information we're complimenting it.
The imaging approaches fiber scan and EMR elastography.
Created a holistic picture for lack of a better word of how we are impacting the disease.
At the foundation of it all is.
Essentially financing the June two reduced abnormal protein, allowing delivered to start healing and were encouraged to see from the early Ireland data that.
Like was previously described model hepatitis there seems to be.
I'm so busy that this happens in a day liberty.
Got it okay, great. Thanks.
Thanks Robyn.
Next one on the line is K K from charging you're in our lives.
Oh, Thanks, just a couple of quick accounting questions be upfront $180 million from the royalty.
How old are you recognizing that.
That will put down the balance she's albeit the herd item in the liability section and then we will recognize.
It proportionate for the current period royalties earned over the proportion over the denominator of the lifetime royalties it'll be a sort of a pro rata recognition overtime.
The life of the patent.
And the and the sales milestones, where you recognize those in the whole once reached.
[noise] day contingent sales milestones for the royalty they will be treated similarly to our others and that they would be added into total transaction price and there'll be sort of a catch up from the proportion recognized overtime. So they wouldn't be single one tie recognition.
Okay. Thanks.
Next one on the line is Jonathan Miller from Evercore, you're in our lives.
Oh, Hey, guys. Thanks for letting me go twice I appreciate it one more thing that I wanted to follow up on from another another analyst question. When you think about X U S ph partners.
What are you looking for any ideal partner there and is there anything in particular on a deal structure that you're most.
Attracted to how would how would you like to.
What sort of a partnership would you like to form accurate.
Yes, I can speak generally about this we're very deep in the process.
At this point in time.
We are looking for a partner that we think that brings excellent rare disease capabilities and a strong history with the with the call point is desirable point as well.
In terms of structure.
This is not a transaction, where we're trying to optimize an upfront payment. This is more something where we're looking for a risk sharing partner.
We're also going to share the upside of successful commercialization in Europe, we're fortunate to be reasonably well funded from a balance sheet perspective and.
Pretty good.
Visibility on a continued cash inflows through collaboration.
And so it was not a case, where where where.
It's not a case, where we're trying to optimize what are the biggest number.
Frontier, but rather what we think is a strong risk share and the and the collaboration.
I think that's probably all it gets an structure at this point.
Great. Thanks, it very helpful.
Alright, we'll take some of them are back or a second bite and I think that's our last question. So I want to thank everybody and thank the operator, hey, as we head into the summer months, we're really excited to have a lot of potential announcements, including <unk> two readouts Fox for Readouts for those around phase one data.
Patient dosing in the face to initiation of that and and <unk>.
NDA filing filing.
Finally per D. C. R. AED initiating that base line study and of course, we're expecting a lily int. This year I am there may be some more things.
That would be the end up announcing the coming months as well so it will be participating in the number of investor conferences in the coming months. So can keep you updated there and also of course on our next call. Thanks for joining us have a great evening.
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