Q3 2023 Agios Pharmaceuticals Inc Earnings Call
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Good day and thank you for standing by welcome to the <unk> Pharmaceuticals incorporated quarter. Three 2023 earnings conference call. At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.
To ask a question during the session you will need to press star one on your telephone.
We'll then hear an automated message advising that your hand is raised.
Please be advised that today's conference is being recorded.
I would now like to hand, the conference over to Mr. Chris Taylor, VP Investor Relations and corporate Communications. Please go ahead.
Thank you operator.
Everyone and welcome to Rga's third quarter 2023 conference call you can access slides for today's call by going to the investors section of our website at <unk> Dot com.
On today's call I am joined by our Chief Executive Officer, Brian Goff, Dr. Sarah Hewins, Chief Medical Officer, and head of research and development set up no one knows about our chief commercial officer, and Phacelia Jones, Chief Financial Officer.
Before we get started I would like to remind everyone that some of the statements. We make on this call will include some forward looking statements actual events and results could differ materially from these expressed or implied by any forward looking statements as a result of various risks uncertainties and other factors, including those set forth in our.
Our most recent filings with the SEC and any other future filings that we may make with the SEC.
And with that I'll turn the call over to Brian. Thanks.
Thanks, Chris Good morning, everyone and thank you for joining us our vision for <unk> is to build a leading hematology franchise with approvals spanning multiple indications and expanded portfolio fueled by disciplined business development and advancement of an internal pipeline aligned with our core expertise in rare disease.
We're excited to speak with you today to review our progress thus far this year and highlight a number of important near term clinical and regulatory milestones in the months ahead.
Our momentum has been building in our accomplishments have been many clinically commercially and in strategic business development.
Most importantly, we have meaningfully advanced our pipeline through excellent execution in clinical development generation of consistent and compelling clinical data and investigators' enthusiasm for the potential of PK activation in our lead indications.
In addition to the milestones achieved to date I am pleased to announce that we have recently dosed. The first patient in the phase III portion of the rise up study of mid tier that in sickle cell disease.
And completed enrollment of the phase III activate <unk> T study admitted to that in pediatric PK deficiency ahead of schedule.
With this progress we are on track to deliver six mid to late stage data readouts by the end of 2025, including three by the end of next year.
And we remain well positioned to generate significant value over both the near and long term Sarah will provide a detailed update on our progress in R&D in just a few minutes.
As Youll hear from Sara we remain encouraged that the durable efficacy observed in the clinical trials admitted to that in PK deficiency has continued to translate to a low discontinuation rate among patients in the real world.
Importantly, we continue to maximize the current launch in PK deficiency, while strengthening our commercial capabilities to support anticipated future launches in meaningfully larger patient populations, including a potential launch in thalassemia in 2025.
As Youll hear from Cecilia, we ended the third quarter with approximately $872 million in cash and investments on the balance sheet. We.
We are very pleased to have added a promising early stage SA RNA asset from El <unk> Island last quarter, and we continue to explore opportunities to expand and diversify our pipeline in a disciplined fashion.
We're also keenly tracking surveys progress towards FDA approval of <unk>, given our retained economics.
Looking at the path ahead, we are on track to achieve each of our remaining 2023 milestones and advanced priorities for next year specifically.
Specifically, we're focused on reporting topline data from the Phase Iia study of AG 946 in lower risk Mds by year end.
And also by the end of this year, we plan to file the IND for our ph stabilizer for the treatment of phenylketonuria or PKU.
Our other priorities moving into next year include preparing for two phase III data readouts for energized and energized and thalassemia next year.
Ramping enrolment in the phase III portion of the rise up study of <unk> in sickle cell disease.
And completing enrollment in the phase III activate kids study of <unk> in pediatric PK deficiency.
Overall I am very pleased with the significant progress we've made in 2023 and I look forward to finishing the year strong with that I'll now turn the call over to Sarah.
Thanks, Brian.
We have made tremendous progress advancing our industry, leading pipeline of PK activator. So far this year and I'd like to thank our research and development team for their dedication and relentless focus on improving patient lives.
Reflecting this progress we are very excited for the upcoming Ash annual meeting in December and look forward to interacting with many stakeholders on our progress in PK deficiency thalassemia sickle cell disease patient advocacy and more we anticipate sharing additional details of our ash abstract when they go live later this morning.
As some of you may have noticed in the online program for Ash for the first time Congress organizers have dedicated an educational session to PK activation as a treatment for hereditary hemolytic anemia entitled Energizing, the Red cell novel therapy for hereditary hemolytic anemia.
This session will include presentations from leading kols on the therapeutic potential of <unk> expectation in PK deficiency, sickle cell disease and thalassemia at.
As the leader I think PK activation, we we're obviously thrilled to see this recognition.
As Brian mentioned, we recently dosed the first patient in the phase III portion of the wrap it study of we talked about in sickle cell disease and the team is working diligently to bring sites on board.
The importance of our efforts with reinforced just a couple of weeks ago as Brian and I had the opportunity to participate in the sickle cell disease Association of America National Convention in the DC area.
We were able to further strengthen our connection with the sickle cell disease patient community by listening to the everyday challenges. These patients face in their lives and reinforce our commitment to patient advocacy and clinical progress.
Switching to our second speaker activator AG 906, given the accelerated enrollment of the phase Iia study in lower risk Mds, We expect to report top line data from this study by the end of this year.
As a reminder, Mds is a heterogeneous group of rare hematological malignancies characterized by ineffective erythropoiesis, commonly leading to anemia importantly, lower risk Mds accounts for approximately 70% of Mds cases, Ishares core pathophysiological features with other hematological diseases in our pipeline.
This phase Iia is a 16 week study in 20 patients and the primary endpoints are hemoglobin response defined as an average increase of at least one five grams per deciliter from baseline from week eight to week, 16, and or transfusion independence defined as remaining transfusion free for at least eight consecutive weeks.
The primary objective of this study is to establish proof of concept for <unk> in participants with low risk Mds and through analysis of the results determine if any protocol adjustments would be appropriate as we contemplate proceeding with phase II.
As Brian mentioned briefly we are on track to achieve all of our remaining 2023 milestones we expect to file the IND for our final element hydroxylase or ph stabilizer to address the underlying cause of <unk> PKU by the end of the year.
Pediatric study's enrollment in the phase III activates T study of Middleby bucked in children with PK deficiency, who are regularly transfused is now complete several months ahead of schedule.
In the complementary study the phase III activate study of <unk> in children with PK deficiency, who are not regularly transfused our team achieved our goal of enrolling at least half of the patients in the study by year end and is now focused on completing enrollment.
Finally, the <unk> W. Recently in licensed from <unk> Island has been integrated into our portfolio and our team is excited to begin advancing that program as a potential disease modifying treatment for polycythemia Vera.
Looking ahead to next year, we expect to report topline results from the phase III energized and energize the studies of metastasis in thalassemia.
Together. These studies are evaluating the top is up across all thalassemia subtypes, including both alpha and beta thalassemia patients in combating the full range of transfusion burden.
For energize, our primary endpoint of hemoglobin response defined as an equal or more one gram per deciliter increase in average hemoglobin concentrations from week 12 through week 24, compared with baseline for energized. The primary endpoint is transfusion reduction response defined as a 50% or greater reduction in <unk>.
Red blood cell units with a reduction of equal or more than two units of transfused red blood cells in any consecutive 12 week period through week 48, compared with baseline.
The design of these trials allows us to demonstrate clinical meaningfulness in a variety of ways via hemoglobin increase supported by a reduction in critique and or transfusion reduction.
Following the strong pace of enrollment we expect data from the <unk> study in the first half of next year and data from <unk> in the second half of next year with that I will now turn the call over to setup.
Thank you Sarah.
Our commercial organization remains focused on maximizing the opportunity of the current launch in PK deficiency, which we will lay the foundation for potential future launches into lithemia sickle cell disease and lower risk Mds.
In the third quarter of 2023, we generated $7 4 million in net <unk> revenue at 10% increase over the prior quarter.
A total of 160 patients had completed a prescription enrolment forum, including 13 in the third quarter of 2023% to 9% increase versus the second quarter.
This translated into net 100 patients on therapy at the end of Q3.
We continue to observe CES conversion timeline in the range of four to six weeks.
Based on from therapy continued to stem from our growing and diverse prescriber base of 142 physicians and represents a broad demographic and disease disease manifestation range that is consistent with the adult PK deficiency population.
We continue to expect slow and steady uptake all of our time and variability quarter over quarter.
This is due to the ultra rare nature of this disease and the long lead time between identifying a potential prescriber and then converting into upbeat and ultimately a patient on therapy.
We remain focused on efficiently identifying providers likely to treat adult patients with PK deficiency and continue to be encouraged with the persistency of patient treatment.
All of our work to build capabilities and targeting analytics physician awareness and education and patient access is helping to build a strong foundation to maximize the opportunity of potential future launches in meaningfully larger patient populations.
The first of these anticipated launches is Intel lithemia, whereas <unk> has the potential to become the first therapy to improve hemolytic anemia, and ineffective erythropoiesis across the full range of disease subtypes.
Including Alpha and beta thalassemia, and transfusion dependent and non transfusion dependent thalassemia.
Importantly, unmet need across the Lithemia subprime remains high approximately 60% of thalassemia patients in the U S do not have an approved treatment option.
As highlighted on this slide in contrast to begin deficiency that the lithemia market in the U S is better established with a higher diagnosed prevalence and higher disease awareness.
Speaking of deficiency is an ultra rare disease, which includes approximately 3000 patients with an estimated diagnosis rate of 30%. In contrast, the lithemia impact approximately 8000 patients in the U S.
The diagnosis rate portal is EMEA is high given the availability of targeted newborn screening.
Sweets Arabs and we all.
Now during the go over to Cecilia.
But that's a third order of 2023 financial results can be found in the press release, we should this morning and the more detailed we'd be included in our 10-Q, which would be five later today.
Let me take a moment to provide some context and highlight a few key points.
Third quarter of 2023, net private and revenue was $7.4 million, an increase of zero point $7 million compared to 222023 driven.
Driven by the variability that's fair I spoke to a moment ago third quarter revenue was lower than we anticipated give.
Given the ultra rare nature of the disease and long lead times associated with initiating patients uncertainty, we continue to expect slow and steady growth in order to order very appealing T. As we move forward.
Consistent with other rare disease launches broke 290 is expected to be in the 10% to 20% range on an annual basis.
Cost of sales for the order was zero point $6 million.
Randy expenses or $81.8 million for the third quarter, an increase of $16.9 million compared to the third order of 2022 the.
This increase was primarily driven by the $17.5 million upfront payment 219 am for the temper success it.
SG&A expenses were $25.8 million for the third order a decrease of $3.3 million compared to the third quarter of 2022 that was primarily driven by decreases in stock based compensation expense unprofessional fees.
Ah that reminder, as part of the divestiture of oncology business, describing it we retain rights to a potential 200 million dollar milestone upon F. D. A approved of <unk> and 15% royalties unpretentious <unk>.
We ended the quarter with cash cash equivalents and marketable securities of approximately $872.4 million.
We expect that this balance to go that was anticipated point of revenue interest income and the potential for more exciting milestone. We didn't name of the company to fund or operating expenses of capital expenditures through several value, creating milestones and at least into 2026.
This guidance does not include cash inflows from potential royalties from <unk> commercializing with a fever and outside of the U S. One on one partnerships or other potential strategic business a financial agreement.
We remained focused on creating shareholder value, including by proactively managing our call space and deployment disciplined gotcha location approach as we prepared to support potential future launches a five okay.
As we move toward additional potential while you're breathing monsters in the near term I am confident that are strong balance sheet, we enabled us to execute from a position of strength as we continue to pursue ways to create you hold your bathroom.
I will now turn the call back over to Brian for his closing remarks.
<unk> so far this year, we've made significant progress towards achieving our vision for <unk>.
Look forward to the catalyst rich period ahead of us with read outs in three mid to late stage studies expected by the end of next year.
There's always will continue to strive to be responsible stewards of our balance sheet and evaluate meaningful opportunities for value creation.
Finally, I would like to thank all of our employees for their hard work and dedication to our mission of transforming the lives of patients living with rare diseases.
And all of our partners, including the patients physicians caregivers and participants in clinical development programs with that will open the call for questions.
Thank you as a reminder to ask a question you will need to press star one one on your telephone. Please stand by will be compiled the candy roster.
Your first question comes from the line of DVR Route from T. D. Calvin Your line is now open.
Hey, guys. Thanks for taking my question. This is Cynthia on per month Uhm Congrats on record.
Just in terms of B N D asked to read out could you give us a little bit more color on the scope is that read out uhm.
Does the team have any I guess internal bar for what success looks like and what's needed what what you need to see before moving into the T. Three potion.
<unk> sure.
So.
As we mentioned so behalf sped up the enrollment of this program, allowing us to create can read out this year by the end of this year and what you can expect this sort of consistent how we've handled top line data results in the past so more to come on that obviously full details will.
Always guard for a medical meeting so.
That would be in the works to in regards to your question.
Four do we have a bar, yes, we do have a bar now this is a phase two eighth of course, we're looking at this study provide us learnings M. As we've mentioned we will make sure that the data is reviewed and that we set up to fail to be for maximum success and I just wanted to take an opportune.
80 to acknowledge again that this is Sarah and her team delivering because this was originally something that we were expecting next year rolled a lot faster than we expected. So we're very much looking forward to the Rio.
Thank you.
Sure.
Your next question comes from the line of solving Victor from Goldman Sachs. Your line is now open.
Hi, This is lydia on for solving I'm kind of going off the last question could you just lay out the opportunity for a G 946, and how it fits within the broader pipeline and in the context of <unk>.
Yeah, maybe I'll take that one first of all I think we're in a great position to have more than one T K activator.
And for a number of reasons Iras actually one of them that it gives us a lot of optionality.
Cause you know we're currently pursuing 946 in two different pathways, Sarah just talked about one which is our pursuit of a low risk M. B said, we're very excited to have the opportunity to get the data read out. The other is we're pursuing 946 in sickle cell disease of the phase one.
Study and the <unk>.
Maintenance is there is to get data in another hemolytic anemia.
Based on what that read out looks like at the right time that'll guide us as to what else, we would like to do with 946, but again from from an overall perspective, a franchise perspective, we have a lot of optionality and several different opportunities in front of us.
Please stand by.
Your next question is from the line of tests Romero from from J P. Morgan. Your line is now open.
[noise] good morning, <unk>. Thanks, so much for taking my question can you give us a sense of the type of analyses, we will get in the full presentation arrive at a medical meeting meeting later this year that are beyond what we saw in the top line.
Thank you.
Sure. That's so as you can expect from US as we always do for our data Readouts. We will provide you with more detail on our secondary endpoints, because we did not provide that yet in the press release.
So you'll see more detail around hemolytic parameter and things like that and then of course safety as well.
For our usual approach, we stick to our intent to treat so you will see exactly the primary and secondary endpoints. The way we had described them in the protocol.
Okay, and looking forward to ask <unk> little bit here and thanks for taking your question.
We are too thanks to us.
Your next question comes from the lines, Greg <unk> from RBC capital markets. Your line is now open.
Hi, This is support on Greg and congrats on the progress half of questions on a G. 946 first can you remind us and you mentioned earlier that day of heterogeneity in Dolores M. D. S. But can you remind us the difference between patients, none transfuse or no burden of prostitution.
Hi burden of transfusion there'll be included in phase two be and why do mechanics them off.
946, you know could address for populations and secondarily no that was a question from the bar for success earlier, but he asked the question in a different way I was wondering if maybe you should look for this partnership early data you know with 30% to 40%, obviously transmission independent at the bar farcical pregnant for.
Competitiveness. Thank you.
Oh, thanks for the questions. So these are I'll start with the last part so.
Can't really compare trial to trial. They are not designed like head to head comparisons there is different in the population enroll there are different in the duration of the trial. So I don't think you can just.
Take a bar from another trial and apply to the next.
In regards to the population. So the first part is a short duration trial in which we chose to and focus.
A population that is less transfused. So we can truly examine what happens there and then the two b is a longer trial in which we feel comfortable to enroll a higher burden a transfusion burthen population.
It is truly just a numerical cut off between all of those different populations and that's it.
Got it thank you.
Yeah.
Our next question comes from the line if Greg Harrison This bank of America. Your line is now open.
Good morning, and thanks for taking the question.
How are you thinking about the incremental commercial opportunity in pediatric P. K D.
How well are these patients characterized.
And what efforts remain on your end for identification and would you expect a lot here to have a similar kittens to what you've seen the adults.
Hey, Thanks for the question absolutely. So when you look at the peak peek a the patient population in totality. We now we expect to have about 328000 patients in the U S. N E O five so it's around 3000 patients in the U S 80% of adults.
Are estimated to be patient population, so it's about 20% of the pediatrics.
And given the outro radar nature of the disease would expect a very similar laundry dynamics, having said that.
There'll be will be on the market for a lot longer with a higher experience with viral kind and understanding of the disease. So we'll we'll be hoping to reach these patients quickly as possible.
And Greg I'll, just add to that in addition.
Issue too.
The commercial opportunity that spread is talking about we also think it's really important to.
<unk> studies conducted and completed in PK D. Because it gives a really nice signal of safety as we look ahead to these meaningfully larger opportunities that we talked about all the time thalassemia sickle cell disease.
So that's the other dimension of this that.
I think for the community the investigators the patients who will be watching we're very enthusiastic about getting those data readouts.
Thanks. That's that's helpful are you able to provide any additional color on discontinuations at this point in the launcher.
If you can quantify it now is there any time in the future or we'd be able to expect that.
So as we said in the past week, we continue to make progress with the launch and learn every day given the outer a rare disease nature of decay D. We would expect to see slow and steady progress over time, but also a very ability quarter over.
Walter I can download it very importantly, we continue to see strength in patients persistency, we'd get positive provide that feedback and pay our support for the product. So the discontinuation rate continued to remain low.
We're dealing with some small based on numbers and that's why you might see some of the changes in the matrix is here.
And to add to that the discontinuation into clinical trials for you know also inflow and that allows us to really study maintenance of affecting the different opal able extension that we have ah ongoing as well and that remains encouraging.
Got it thanks again for taking my question.
Thank you Greg.
Your next question is from the line of Daniel <unk> from Raymond James Your line is open.
Hey, guys. This is Alexandra Danielle another question on 946, I hope it will be us data I'm just curious what your updated thoughts on how big you think of the thrombocytopenia.
Risk is of the toxicity signal I know you're not using the same dose where it emerged but he was kind of curious if there's anything particular about M. P. S that could make me patients more susceptible to that signal.
Sure. Thanks for the question so.
Start with the second part of your question. So thrombocytopenia is indeed more common in patients living with Mds because they they they can be prone to develop <unk>, which includes with decreasing platelets that spark of their disease and indeed, many of the therapies have trouble cytopenia as an additional.
The first event reports it.
To your point, we did observe thrombocytopenia at the high high tools.
The 20 milligram dose in healthy volunteers.
Right now we are studying five milligrams and the Mds patient population and we're working to really understand the safety profile inefficacy profile of the drug so more to come on that after we have a database lock.
And Sarah often add to the phrase that this is it's monitor role, it's manageable and it's reversal very which is which is very encouraging as well indeed.
That's the thing we hear really from a physician as well because.
This is something that actually occurs within the Oregon system that they are very comfortable with right. They're treating all of these mythological conditions affect us from a cytopenia is something that can be picked up a lap draws and then mitigated by a potential discontinuation is is a very reassuring thing.
Thank you now I would like to turn the call back to Brian Golf for closing comment.
Well. Thank you all very much for participating in today's call have you heard this morning, our team has great conviction inner potential to deliver transformative new therapies for patients.
And significant long long term value for shareholders.
Really proud of the efforts that continued efforts from our team. So we appreciate your interest in our jails and very much look forward to speaking with you soon thanks a lot.
This concludes today's conference call. Thank all for participating you may disconnect.
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