Post by luxetvox on Jan 10, 2023 18:10:36 GMT
I was mistaken when I shouted yesterday that ASND was presenting at JPM today. Thinking about it last night, the rather significant drop in price in the Monday session made me think I had the date wrong. I did. They presented yesterday, and clearly what was said, or wasn't said, didn't sit well with investors. Sure enough I checked Bloomberg this morning, and voila.....yesterday's dog and pony show was in the news feed. To be clear, I did not read the entire thing (much of it transcribed in such a way as to be unintelligible); I only word searched for Skytrofa. So, allowing that the CEO may have laid an egg or two in the info he relayed for other products and clinical programs, I think he was less than impressive, in fact rather generic in several instances, regarding his updates about Skytrofa. Noteworthy to me was his answer to JPM's final question about "a long acting competitor (to Skytrofa) coming to market..." I'm admittedly biased, but his answer wasn't very convincing.
This sentence from the text's accompanying disclaimer is an understatement: "This transcript may not be 100 percent accurate and may contain misspellings and other inaccuracies."
Jessica Fye:
Great. Good morning, everyone. My name is Jess Fye. I'm a large-cap biotech
analyst at JPMorgan, and we're delighted to be continuing the conference this
morning with Ascendis Pharma.
Presenting for the company is going to be their CEO, Jan Mikkelsen. But
before I pass it over to him, we're going to let Tim Lee from IR come up and
do the forward-looking statement.
Timothy J. Lee, Senior Director, Investor Relations:
Good morning. Before we begin, I'd like to remind you this presentation will
contain forward-looking statements, and our actual results and events could
differ materially from those in the forward-looking statements. For
additional information concerning the factors that cause actual results to
differ materially, please see our forward-looking statements section in the
press release from yesterday and our SEC filings for the associated risk
factors.
With that, Jan.
Jan Moller Mikkelsen, President and Chief Executive Officer:
Thanks a lot, Tim. It's a pleasure to be here. It's nice to see people again
face-to-face. I will make it short today, just to focus on a few items today,
which I think that is the key message we would like to come up with and also
giving you a lot of opportunities and time really to answer questions.
So, there was what Tim covered in that presentation. So, we really focus on
the patient life, and we're building sustainable value. This is what we
always have done in our strategic framework, first, our Vision 20-20, now our
Vision 3x3.
Coming to our global sec, yes, we are a global company. We want to think
global, we want to be global, we will where the patients are. Everything we
do is built on the TransCon technology. But TransCon technology is not a
stational technology. It's quite different from when we started for about 15
years ago. We have expanded to the third, fourth, fifth generation. We had at
the same time being in a position, we have expanded not only to have our,
what we call our soluble polymer technology, but also to the hydrogel, which
we actually apply now both in oncology and also in our new therapeutic area
ophthalmology.
What is the core of TransCon technology? It's basically a combination of a
classical product technology and is predictable sustained with this
technology. Combining these two elements you have the TransCon technology.
This is why when we start with a parent drug that basic have proven clinical
data, proven safety data, proven biological action. When we take it into the
system, we release the same unmodified entity. This is what we used in
TransCon growth hormone, daily growth hormone, the same in adult growth
hormone.
PTH, TransCon PTH, we use Forteo PTH 1-34. TransCon CNP, we're using the same
thing. This is why we expect that we basic will be in a position, we have
this high success rate because when you think about, we started with three
preclinical candidate TransCon Growth Hormone, TransCon PTH, TransCon CNP in
rare disease endocrinology. We are in a position now. TransCon Growth Hormone
is approved with SKYTROFA in U.S. and Europe.
We have priority review with TransCon PTH, and we expect an approval of
TransCon CNP in 2025, mainly because we can get and hope three out of three
because we not have the hydrological risk. But we're not compromising that
really making a highly differentiated product opportunities. No one else can
make really addressing major unmet medical needs.
This is the algorithm we have built up on that, which actually explains
exactly what I did. So, this is the pipeline we have built up. So, going to
our vision. This is the vision I presented to test. In 2019, we call it
Vision 3x3, building a leading global biopharma company. You can really
imagine one year from now on, we will have a new vision. I have not the name
yet. It will not be Vision 5x5, it will be too boring.
So, we will find a new, new way. But what we did, there was our strategic
pathway and that is what we really have executed on in a time full manner. We
had that we wanted to have growth hormone approved in '21. We got approved.
We expect PTH to be approved in '23. That is what we hope to do. CNP, in '25.
That was our plan from 2019.
Global clinical reach, we have done it, pursue 9 indications, because to
develop number one brand you need to invest, and this is what we're doing in
both in label optimization, life cycle management, like TransCon PTH. We now
have both a daily and a once weekly product. And we focus on new
endocrinology product, which I always get asked, always get asked, do you
expand out from rare disease endocrinology because we are classical -- coming
from a classical endocrinology company, which makes a lot of sense for us,
but that will come in our next vision.
Go to our oncology, because I want to keep the commercial thing, because I'm
just aware of the main focus on SKYTROFA. So, when I come to SKYTROFA, I will
focus on that. Oncology, we're really making two highly differentiated
products, which are now coming to the really, really interesting stage, where
we have recommended Phase 2, and we are expanding in what we call expanding
in single indication. And the third therapeutic area, we announced, and I
will come with a few words about that.
Going to SKYTROFA. SKYTROFA, why it's best-in-class product opportunities?
Because for more than 25 years, people have tried to develop and address the
unmet medical need. Why do you have a poor outcome in pediatric growth
hormone deficiency? The primary endpoint has always been high. We are the
only long acting growth hormone that work within somatropin, the same as in
adult growth hormone, the same as daily growth hormone. This is why when we
look on all the endocrine benefit you expect to have of the treatment related
to body composition, I'll come back to that. Mental health, cardiovascular
disease, fracture, we believe we will achieve all that because we're not
changing the mode of action.
And this is what we see in the U.S. We see how we highly differentiated to
the daily growth hormone. A classical patient from us today, because we have
one commercial strategy, when we wanted to go in, was to focus on one single
element how to build SKYTROFA to the leading brand in value in a growing
growth hormone market, and as a highly profitable product. There was a three
pillar. We launched SKYTROFA. And in Q2, I got asked what is -- do you come
with forward-looking related to revenue and say, no, we don't do it, but I
can give you a simple algorithm. I said, you know, we saw what we did in Q1.
I expect we can double rest of the year.
So, in my mathematic algorithm is 2, 4, 8, 16, and we really achieved that.
Much better than we actually have hoped for, much better that we thought so.
We're still doing a lot of action to really, really, really move into a
situation, where we're getting more and more patients reimbursed.
So, what is the great part of this treatment instead? When a patient come on
treatment, the typical will have a duration through four to five years. When
I look at the patients, how many dropouts do we have? We have basics zero.
So, when you think about and ask me, what is your algorithm now from '23. I
will make it simple again from a mathematic perspective. Yes, we have 17.1 or
17.5 related to FX. It gives you -- multiply that before, then you basically
have a baseline for the patient we have already established in '22. Then we
will add on, which I believe at least the same amount of patient and
reimbursed patient in '23.
I think it's a really simple algorithm, which I feel pretty confident on. I
have no doubt that what we have with SKYTROFA and how we're progressing. We
can do it on a global basis. This is why we launching SKYTROFA now in the
U.S., in Europe next year. We have a very interesting trial coming out next
year in adult growth hormone deficiency is the trial, where we basically have
three arms. We want to prove that we not only are better than placebo, but
also will be in a position that we potentially like we did on the primary
endpoint in adult, which are body composition, we also can have a potential
superior product.
This is why we have one-to-one between daily growth hormone, placebo and
SKYTROFA. You don't get a leading global brand without investment. And this
is what we're doing. We do label expansion. We have not only at our adult
growth hormone deficiency trial. We also have a turner. We have also combined
it with CNP because we are the only company that have two pillars in growth
disorder, TransCon CNP, TransCon Growth Hormone, both of them are the pillars
in more than 20-plus growth disorder. Some of them will be best treated with
TransCon Growth Hormone, some will be best treated with TransCon CNP. Some of
them will need a combination in different durations.
And this is why we can be the leading global company in growth disorder. We
will launch in Europe. Do what we did in U.S., start launching SKYTROFA next
year, in the middle of the year in Europe. We have our Asian strategy, where
we're both finalizing the trials in China and Japan to be quite sure we also
go as a global leader.
This with the summary, our next step, I think I have really seen. The current
market today is a $4 billion, global, growing, and we believe we can increase
that market. So, coming to PTH. I will bring a lot of attention to PTH. When
I have heard the patient story, when I see what the benefit we give to the
patients. How the physicians are reacting, how the patients are staying on
our trial? I have never seen a product like that. When you see of this series
of morbidities, I understand that because we basically are addressing all of
them, because we're doing a normalization of physiological PTHs. It will be
thinking about having a type 1 diabetes patient and not be in position to
give them a basal insulin. This is how this patient improve. [ph] This is
80,000 to 100,000 patients just in the U.S.
Going to our trials. We actually have three trials now. We have our Phase 2,
our Phase 3 and we have our Phase 3 in Japan. All of them show everything,
what we have (inaudible), and even in all the different demographics, you can
see the Japanese trial is a little bit different, because we have a much
higher level of the genetic. For example, we have more ADH1 patients, which
are hard to find, because not many of them are really diagnosed as what we
call chronic HP patient. And when we go out and look on the results, it
pretty
is impressive. Number of patients eliminate convention therapy.
Why is that really important? Because eliminate the conventional therapy is
absolute eliminating part of the cause of the disease, because the number a
high level of active vitamin D, calcium supplement is basic part of
facilitating the disease and many of its core morbidities. This is why it's
so important to eliminate current conventional therapy and you can see
independent of active vitamin D basic 100 and nearly more than 90% went into
basic to be in position that you only took a multivitamin tablet, which are
600 milligram, like Cosco [ph] tablet, really impressive. And every element
we looked on, we really see how it's benefited.
Going to the Japanese trial, I just wanted to show from a single side. I like
this, because it really illustrates that even if you go to Japan, which have
very different way to treat hypopara that take much higher active Vitamin D.
You can see they have really high serum phosphate. And as soon as we
normalize them, you can see normalization all the time.
This is the patient population we have just in the U.S. We have priority
review. We are in a position. We have an expanded access program now. We
established -- we have a press release last week when we starting enroll
patients. I believe the way that FDA had giving us help, how they are helping
the patient, recognize that there was a product in the market that got taken
away. And now the last patient that is on a compression use will be taken off
of that product in '24.
I believe there is such a huge unmet medical need that is really got
recognized. 4,000 to 5,000 patients are PTH experience. This is the patient
group we really want to go into our expanded access program as fast as
possible, because they are used -- basic to use PTHs. And then we have the
65,000 to 80,000 patients, which are the patients that mainly got recruited
into a Phase 2 and Phase 3 trial. Newly diagnosed more than 3,000 a year. So,
this is a group of patient that will expand year-by-year.
So, what also was a key element last year was the change in guidelines. The
basic come out with a recommendation in the last guideline that if you have
any non-controlled in any of the following symptomatic hypocalcemia
hypophosphatemia, renal insufficiency, hypercalciuria, poor quality of life
with exiting this 95% of the patient, then you should go to PTHs, which gives
me also confident that we will have a strong frontman to get a really optimal
market assessed situation. So, this is our next step. We have still 146 out
of 145, with patients up to three years, pretty impressive. Some of them thus
that was on the placebo treatment.
I will move directly over to one single slide here. I will not go into some
of CNP. If someone doing the Q&A, I can take some of the slide -- now I went
too fast, now we need to go back. I want to say one thing on oncology. We are
working on two unique compound in oncology, a kick starter of the
immunological system, where we use the hydro technology to take it into the
tumor.
The other one is general IL-2 beta or gamma. And you will be tired on looking
and hearing about an IL-2 compound because there have been 25 companies. I
think why does 25 company because people recognize the benefit that it can
provide if it succeeds.
We have moved, brought product to a state, where we have recommended Phase 2
on our TransCon TLR7 by 8 Agonist. We actually have accelerated our IL-2 beta
or gamma much more far than we ever thought about because of the safety and
tolerability. And it's not because we are compromising efficacy. And this is
what I believe, when we come here in the beginning of next year, we will
declare recommended Phase 2 also for our TransCon IL-2 and I really want to
look forward to give you the data that really show how this also is a
(inaudible) product.
So ophthalmology, why did we select ophthalmology? We selected ophthalmology
up from that because we have a TransCon technology platform that basically
can give us product opportunities that no one else can make, make them so
highly differentiated. But because we can have a continuous local release
back in the eyes, not for months, not for two months. I will give you the
curve. When I look on ranibizumab, also known as Lucentis, which both have
been used as a, what we call direct injection, but also in an implant.
We are in a position that we can make and really address the high unmet
medical need that is still in this $10 billion plus sector, because that is
still patient getting blind, cannot comply with the treatment because of the
huge burden. This clinical validated programs, the compound is one it fit
directly our algorithm, like we had in rare disease at endocrinology, where
we expect three out of three.
Going to our data. What we did, this is the best model. For first time thing,
you need to look on the injection volume, 50-microliter, we injected. We can
see, when we inject the 50-microliter, we are in a position that we are
having coverage over the target level, because it's pretty well known what
target level you need to be on always to have sufficient anti-VEGF
neutralization. And we can see we can have it more than 18 months. This
technology platform open up for a lot of product opportunities that basically
could be a pipeline as we have in rare disease endocrinology, but in a much
larger market segment.
Going to our milestones for 2023. If I look on growth hormone and our only
take selected milestone after all the milestones, because you can read the
slides. What I really look forward to is our adult growth hormone data in the
foresiGHt Trial in Q4. The key program, where we will see a major development
next year from commercialization will be our TransCon PTH. We have priority
review, the 13 of April. We are in tense interaction with regulatory
agencies, both in Europe and U.S. We expect still to keep this timeline. This
is a combination product, but it is also building on a lot of proven
technology.
And we expect to launch directly afterwards. We're ready, we're
manufacturing. Everything is built up. The first wave of sales force is
established higher out there. End of the year Q4, we will get a decision from
Europe. Europe, that is still the same high unmet medical need as the only
approved product there will also disappear in '24. CMP, we got what we hope
for in all our data, the four pillar, safety, efficacy, tolerability and
convenience. No doubt, we believe this is the best-in-class product
opportunity. We are enrolling a 2b, which we hope is a pivotal trial. We will
be in a position that we aligning all the patients, because there is a huge
unmet medical need and a huge awareness about what is the profile. So, we
expect that we can enroll the entire trial in four, five months, never
happened before.
Going to the oncology, you can see lot of blue marks because in '23, we
really move into the indication expansion. And we will have the first
analysis, which will continue into '24, where we really hope to prove that we
have a paradigm shift in all our treatment.
Yes, thanks a lot for giving me the opportunity to present today.
Questions And Answers
Jessica Fye:
(Question And Answer)
Jessica Fye:
Great. So we're going to start Q&A here. You can raise your hand and someone
will bring you a mic or you can submit a question electronically, and I can
read it off the iPad upfront, but I'll start.
So, on your ophthalmology vertical, can you talk about how your technology is
differentiated from past efforts to make long-acting drugs for the eye?
Jan Moller Mikkelsen, President and Chief Executive Officer:
So, currently what you're doing is that, if you want to make it longer
acting, you can nearly see going for Lucentis to (Technical Difficulty) you
can also say the Kodiak [ph] approach is to make the molecule larger and
larger, but you still doing a bolus injection. It meaning that you very much
is dependent on how fast back in the eyes, it's clearing the compound. And
when you get older, when you have many of this disease, you have much faster
clearing.
So, what we are doing is basically applying complete paradigm shift, where we
are building particles that sit in hyaluronic acid inside back of the eyes on
a continuous manner day-by-day release an unmodified ranibizumab molecule. By
doing that we total independent on the clearance in back of the eyes. And
when we look on the profile we have, the profile, in my view, is providing
two interesting elements in providing a higher concentration for more than
six months, much, much higher than you really are taking as the target
concentration.
Just look at the half-life 100 days. At the same time, it's extremely
well-tolerated, meaning is that it opened up for many opportunities. It
opened up for an opportunity to have better efficacy, better safety because
of the risk of injection and tolerability, but also not for combination
therapy, because no one can inject in back of the eyes multiple compound on a
twice monthly manner or every third month.
So, it both is an enabling technology, technology for combination product,
but also acts just anti-VEGF treatment as our TransCon ranibizumab, a profile
that never have been seen before, a profile that address one of the key
element of inter-patient variability of clearance. So, it's really is a
paradigm shift.
Ken, do you have?
Kennett Sprogoe, Executive Vice President, Head of Innovation and Research:
Yes. Maybe just a couple of parts. When we talk to retinal specialists, what
they mostly are concerned about is actually not new biology. It's extending
the duration of action, because people -- if you have seen somebody get an
intravitreal injection, you understand, why you don't want to be taking this
on a monthly basis. So, if you can extend it to every six months, you're much
more likely to keep patients on drug and keep them above that critical level
you need for VEGF neutralization. So to me, also this area reminds me a lot
about our rare disease efforts, because also you can't just make the molecule
larger, because it needs to diffuse to the back of the eye.
The retinas at the very back, you have liquid flow that goes towards the
front of the eye and drains whatever you inject into the vitreous. And
there's abundance of literature showing smaller molecules diffuse better to
the back of the eye. So, being able to release a fab, we would expect to have
much better efficacy at the back of the eye and not just neutralizing
whatever is individual compartment.
So to me, the combination of having a modular platform that allows us to take
multiple different compounds together with releasing something that has the
right size. We know size matters, when it comes to tissue distribution and
then being able to treat patients irrespective of vitreal composition,
because we know it thins with age. So, I think those combined makes the
TransCon hydrogel platform extraordinarily well fitted for localized
treatment of vitreal diseases.
Jan Moller Mikkelsen, President and Chief Executive Officer:
As an introduction. This is Kennett Sprogoe. He is our Head of Research and
Development. He was actually one of founding people, when we founded this
company in 2007. So, he really knows the technology platform in and out and
all the benefit we can get it in all the product opportunity. He's basically
the person that designed all our product opportunities.
Jessica Fye:
So, maybe speaking of other product opportunities, there's been a lot of buzz
and I think maybe some anticipation in the market about Ascendis. Ascendis
applying your capabilities to non-rare endocrinology. I think specifically
folks are sort of hoping you'll work on GLP-1 and get into the obesity space.
We obviously didn't hear something on that today. Is that on the table is
something Ascendis might pursue going to kind of more prevalent endocrine
conditions?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I think it's two different discussions. What we had in our Vision 3x3 was to
move out to three different therapeutic areas there from a strategic
perspective. And that is what we did by moving into ophthalmology, because we
really can build up a pipeline in a huge, huge market segment of highly
differentiated product that really will be best-in-class, really addressing
some real unmet medical need. We are in rare disease endocrinology. And if we
go outside and remove rare, for me, it's just something I would do and not
really discuss it before this competitive environment that is that before I
have data, not waiting to say 18 months before we move into clinical
development or anything like that.
It's a highly competitive area, I'm here to win. I'm not here to give any
advancement to any competitor. If we do it, we will do it. If we feel that
somebody is fitting our pipeline, it's fitting the benefit of the patient,
it's fitting the benefit of value creation, we will do it.
Jessica Fye:
We got a question in my e-mail about PTH and maybe I'll wrap it in with
another question that I was going to ask on the product. So, you're starting
this expanded access to help patients initiate on TransCon PTH prior to the
approval. And presumably, that's create a favorable launch dynamic, where
you'll then be able to convert them over.
So, first question is, how do we think about the timing over which
reimbursement for TransCon PTH could ramp up? Should that look different than
TransCon Growth Hormone did?
And second, this is the investor question, what's a good assumption for
TransCon PTH price is not part of -- the right range to think about?
Jan Moller Mikkelsen, President and Chief Executive Officer:
Yes. Let me take the first one, because I think what we did in launch of
SKYTROFA. We had in the war-room, we want to a lot of different strategies,
how do we want to launch SKYTROFA in the U.S. We cannot go the rebate way,
giving a lot of revenue in the beginning, but less profit.
We decided to build on the strength of the product, because we have the
best-in-class product that is highly differentiated to every daily growth
hormone, but also other long acting. So, we took the long term, long staying
to an established market. We didn't go to the classical way to basically
provide a lot of rebate. We went to the medical exemption pathway, because we
didn't accept that the rebate that was given to us.
How can we do it and why we can do it extremely successful, it's because we
have the best-in-class product opportunity that really make a meaningful
differentiation for the patient. So, both our physician and everyone is
willing to take the work to get the medical exemption, because it's really
benefited.
TransCon PTH is completely different. We are launching into a segment, where
the only opportunity that was there is taken away from the market. We are
launching into an air, where there is basic no competition. There is a huge
recognization of the unmet medical need, there is a huge recognization of the
benefit we can provide to the patient, which I think is supported by two
things and I call it validation, the guidelines.
I have never been in a position, never been in a position that basically
before you launch the problem, there is a guideline that's saying that you
should utilize this product for most patients. First time guidelines is
something that come one or two years after launch. The other thing is also
being recognized at least from my perspective, is as recognized to the
regulatory agencies by providing us a priority review, providing us the way
of making an expanded program for the patient before we basically can launch
the product really to help the patient.
Yes. Now I forgot the second question.
Jessica Fye:
Price?
Jan Moller Mikkelsen, President and Chief Executive Officer:
Price is something we decide when we -- just before we launch. We're doing a
lot of analysis related to price today. We actually are not compares to
NATPARA. We are thinking about these product opportunities out from a
complete different label that was giving to NATPARA. We are positioned this
product from the benefit we're providing to the patient. And this is how we
think the price structure.
Jessica Fye:
Questions on that? I think consensus is on saying like the $40 million, maybe
$50 million range for TransCon PTH for 2023. Is that a number that you're
comfortable with thinking about the initial the launch ramp?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I think that's always, I like to see and be quite sure, when I come up with
an algorithm. I like all this to come up with algorithm because I'm
mathematic. So, from my perspective is when we come into the launch, when
we're coming in and seeing what we are, I think it's a good timing to give
you some kind of guidance on it.
But just think about it there is 5,000 patients that were used to use PTHs,
5,000 patients in the U.S. People that have experience with using PTH, where
the drug got taken for them. Then you have where we basically recruited in
our Phase 2 and Phase 3, the 80,000 patients, where we now have all of them
basically staying, staying, staying on treatment. What did that tell me? It
tells me all patients will benefit for this treatment. That I think is the
key element.
Jessica Fye:
I think for TransCon CNP, you've talked about filing in the back half of 2024
on the back of your Phase 2b trial. Have you talked to the FDA and confirmed
that they're good with your endpoint and trial design stuff like that?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I think the end point is really well recognized, analyzed growth velocity.
And we're actually doing a simple form of analyzed growth velocity, which is
also recognized by FDA and other regulatory agencies that we're not making a
difference between pretreatment, but just looking on the absolute analyzed
growth velocity. So, the endpoint is pretty, pretty simple.
Our aspiration is not have a labeling on linear growth. Our aspiration is to
have a treatment of achondroplasia and also address the comorbidities. This
is why -- one of the things that's struggling me, we have now accomplished
trial with patients more than two years. What is our retention in our study,
100%, 100% of 57 patients? What are we providing to this patient group that
is not recognized in analyzed growth velocity, because I don't believe that
everyone just believe that getting height is the important thing of
achondroplasia. At least this is my understanding when I talk with parents
and listen to some of the patient group.
What are we giving to them? And that is what we want to qualify in our
pivotal 2b study. So, we can ensure that we also can have that part of our
labeling discussion. And I think that is the key element of what we're doing.
It's pretty clear. No one has any questions.
Jessica Fye:
You talked about SKYTROFA and the nice kind of trajectory that's starting to
emerge there. But I think you could have another long-acting competitor
coming to market as well. How do you think about that competitive dynamic
once you're not the only kind of long-acting growth hormone?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I could think and when we look on the data that is under other long-acting
product and then compared to daily growth hormone. On an absolute level, when
you look on outcome related to a low European dose that could much lower,
just hitting statistic non-inferior on an absolute low. When we go to body
composition, the Phase 3, the basic proof that only have the half of the
activity compared to daily growth hormone.
When I see our SKYTROFA, we're highly differentiated, best-in-class, we had
an analyzed growth velocity that was a statistic higher than the one we got
from daily growth group. We hope we can show the same thing in body
composition.
And this is why I'm not really believing it's changing anything, because we
basically will be in the best-in-class product opportunity potentially would
change a little bit how much that is left of daily growth hormone. It's not
changing any of our basic forecast.
Jessica Fye:
Great. Well, we're about out of time, so I'll leave it there. Thank you.
Jan Moller Mikkelsen, President and Chief Executive Officer:
Thank you so much.
This sentence from the text's accompanying disclaimer is an understatement: "This transcript may not be 100 percent accurate and may contain misspellings and other inaccuracies."
Jessica Fye:
Great. Good morning, everyone. My name is Jess Fye. I'm a large-cap biotech
analyst at JPMorgan, and we're delighted to be continuing the conference this
morning with Ascendis Pharma.
Presenting for the company is going to be their CEO, Jan Mikkelsen. But
before I pass it over to him, we're going to let Tim Lee from IR come up and
do the forward-looking statement.
Timothy J. Lee, Senior Director, Investor Relations:
Good morning. Before we begin, I'd like to remind you this presentation will
contain forward-looking statements, and our actual results and events could
differ materially from those in the forward-looking statements. For
additional information concerning the factors that cause actual results to
differ materially, please see our forward-looking statements section in the
press release from yesterday and our SEC filings for the associated risk
factors.
With that, Jan.
Jan Moller Mikkelsen, President and Chief Executive Officer:
Thanks a lot, Tim. It's a pleasure to be here. It's nice to see people again
face-to-face. I will make it short today, just to focus on a few items today,
which I think that is the key message we would like to come up with and also
giving you a lot of opportunities and time really to answer questions.
So, there was what Tim covered in that presentation. So, we really focus on
the patient life, and we're building sustainable value. This is what we
always have done in our strategic framework, first, our Vision 20-20, now our
Vision 3x3.
Coming to our global sec, yes, we are a global company. We want to think
global, we want to be global, we will where the patients are. Everything we
do is built on the TransCon technology. But TransCon technology is not a
stational technology. It's quite different from when we started for about 15
years ago. We have expanded to the third, fourth, fifth generation. We had at
the same time being in a position, we have expanded not only to have our,
what we call our soluble polymer technology, but also to the hydrogel, which
we actually apply now both in oncology and also in our new therapeutic area
ophthalmology.
What is the core of TransCon technology? It's basically a combination of a
classical product technology and is predictable sustained with this
technology. Combining these two elements you have the TransCon technology.
This is why when we start with a parent drug that basic have proven clinical
data, proven safety data, proven biological action. When we take it into the
system, we release the same unmodified entity. This is what we used in
TransCon growth hormone, daily growth hormone, the same in adult growth
hormone.
PTH, TransCon PTH, we use Forteo PTH 1-34. TransCon CNP, we're using the same
thing. This is why we expect that we basic will be in a position, we have
this high success rate because when you think about, we started with three
preclinical candidate TransCon Growth Hormone, TransCon PTH, TransCon CNP in
rare disease endocrinology. We are in a position now. TransCon Growth Hormone
is approved with SKYTROFA in U.S. and Europe.
We have priority review with TransCon PTH, and we expect an approval of
TransCon CNP in 2025, mainly because we can get and hope three out of three
because we not have the hydrological risk. But we're not compromising that
really making a highly differentiated product opportunities. No one else can
make really addressing major unmet medical needs.
This is the algorithm we have built up on that, which actually explains
exactly what I did. So, this is the pipeline we have built up. So, going to
our vision. This is the vision I presented to test. In 2019, we call it
Vision 3x3, building a leading global biopharma company. You can really
imagine one year from now on, we will have a new vision. I have not the name
yet. It will not be Vision 5x5, it will be too boring.
So, we will find a new, new way. But what we did, there was our strategic
pathway and that is what we really have executed on in a time full manner. We
had that we wanted to have growth hormone approved in '21. We got approved.
We expect PTH to be approved in '23. That is what we hope to do. CNP, in '25.
That was our plan from 2019.
Global clinical reach, we have done it, pursue 9 indications, because to
develop number one brand you need to invest, and this is what we're doing in
both in label optimization, life cycle management, like TransCon PTH. We now
have both a daily and a once weekly product. And we focus on new
endocrinology product, which I always get asked, always get asked, do you
expand out from rare disease endocrinology because we are classical -- coming
from a classical endocrinology company, which makes a lot of sense for us,
but that will come in our next vision.
Go to our oncology, because I want to keep the commercial thing, because I'm
just aware of the main focus on SKYTROFA. So, when I come to SKYTROFA, I will
focus on that. Oncology, we're really making two highly differentiated
products, which are now coming to the really, really interesting stage, where
we have recommended Phase 2, and we are expanding in what we call expanding
in single indication. And the third therapeutic area, we announced, and I
will come with a few words about that.
Going to SKYTROFA. SKYTROFA, why it's best-in-class product opportunities?
Because for more than 25 years, people have tried to develop and address the
unmet medical need. Why do you have a poor outcome in pediatric growth
hormone deficiency? The primary endpoint has always been high. We are the
only long acting growth hormone that work within somatropin, the same as in
adult growth hormone, the same as daily growth hormone. This is why when we
look on all the endocrine benefit you expect to have of the treatment related
to body composition, I'll come back to that. Mental health, cardiovascular
disease, fracture, we believe we will achieve all that because we're not
changing the mode of action.
And this is what we see in the U.S. We see how we highly differentiated to
the daily growth hormone. A classical patient from us today, because we have
one commercial strategy, when we wanted to go in, was to focus on one single
element how to build SKYTROFA to the leading brand in value in a growing
growth hormone market, and as a highly profitable product. There was a three
pillar. We launched SKYTROFA. And in Q2, I got asked what is -- do you come
with forward-looking related to revenue and say, no, we don't do it, but I
can give you a simple algorithm. I said, you know, we saw what we did in Q1.
I expect we can double rest of the year.
So, in my mathematic algorithm is 2, 4, 8, 16, and we really achieved that.
Much better than we actually have hoped for, much better that we thought so.
We're still doing a lot of action to really, really, really move into a
situation, where we're getting more and more patients reimbursed.
So, what is the great part of this treatment instead? When a patient come on
treatment, the typical will have a duration through four to five years. When
I look at the patients, how many dropouts do we have? We have basics zero.
So, when you think about and ask me, what is your algorithm now from '23. I
will make it simple again from a mathematic perspective. Yes, we have 17.1 or
17.5 related to FX. It gives you -- multiply that before, then you basically
have a baseline for the patient we have already established in '22. Then we
will add on, which I believe at least the same amount of patient and
reimbursed patient in '23.
I think it's a really simple algorithm, which I feel pretty confident on. I
have no doubt that what we have with SKYTROFA and how we're progressing. We
can do it on a global basis. This is why we launching SKYTROFA now in the
U.S., in Europe next year. We have a very interesting trial coming out next
year in adult growth hormone deficiency is the trial, where we basically have
three arms. We want to prove that we not only are better than placebo, but
also will be in a position that we potentially like we did on the primary
endpoint in adult, which are body composition, we also can have a potential
superior product.
This is why we have one-to-one between daily growth hormone, placebo and
SKYTROFA. You don't get a leading global brand without investment. And this
is what we're doing. We do label expansion. We have not only at our adult
growth hormone deficiency trial. We also have a turner. We have also combined
it with CNP because we are the only company that have two pillars in growth
disorder, TransCon CNP, TransCon Growth Hormone, both of them are the pillars
in more than 20-plus growth disorder. Some of them will be best treated with
TransCon Growth Hormone, some will be best treated with TransCon CNP. Some of
them will need a combination in different durations.
And this is why we can be the leading global company in growth disorder. We
will launch in Europe. Do what we did in U.S., start launching SKYTROFA next
year, in the middle of the year in Europe. We have our Asian strategy, where
we're both finalizing the trials in China and Japan to be quite sure we also
go as a global leader.
This with the summary, our next step, I think I have really seen. The current
market today is a $4 billion, global, growing, and we believe we can increase
that market. So, coming to PTH. I will bring a lot of attention to PTH. When
I have heard the patient story, when I see what the benefit we give to the
patients. How the physicians are reacting, how the patients are staying on
our trial? I have never seen a product like that. When you see of this series
of morbidities, I understand that because we basically are addressing all of
them, because we're doing a normalization of physiological PTHs. It will be
thinking about having a type 1 diabetes patient and not be in position to
give them a basal insulin. This is how this patient improve. [ph] This is
80,000 to 100,000 patients just in the U.S.
Going to our trials. We actually have three trials now. We have our Phase 2,
our Phase 3 and we have our Phase 3 in Japan. All of them show everything,
what we have (inaudible), and even in all the different demographics, you can
see the Japanese trial is a little bit different, because we have a much
higher level of the genetic. For example, we have more ADH1 patients, which
are hard to find, because not many of them are really diagnosed as what we
call chronic HP patient. And when we go out and look on the results, it
pretty
is impressive. Number of patients eliminate convention therapy.
Why is that really important? Because eliminate the conventional therapy is
absolute eliminating part of the cause of the disease, because the number a
high level of active vitamin D, calcium supplement is basic part of
facilitating the disease and many of its core morbidities. This is why it's
so important to eliminate current conventional therapy and you can see
independent of active vitamin D basic 100 and nearly more than 90% went into
basic to be in position that you only took a multivitamin tablet, which are
600 milligram, like Cosco [ph] tablet, really impressive. And every element
we looked on, we really see how it's benefited.
Going to the Japanese trial, I just wanted to show from a single side. I like
this, because it really illustrates that even if you go to Japan, which have
very different way to treat hypopara that take much higher active Vitamin D.
You can see they have really high serum phosphate. And as soon as we
normalize them, you can see normalization all the time.
This is the patient population we have just in the U.S. We have priority
review. We are in a position. We have an expanded access program now. We
established -- we have a press release last week when we starting enroll
patients. I believe the way that FDA had giving us help, how they are helping
the patient, recognize that there was a product in the market that got taken
away. And now the last patient that is on a compression use will be taken off
of that product in '24.
I believe there is such a huge unmet medical need that is really got
recognized. 4,000 to 5,000 patients are PTH experience. This is the patient
group we really want to go into our expanded access program as fast as
possible, because they are used -- basic to use PTHs. And then we have the
65,000 to 80,000 patients, which are the patients that mainly got recruited
into a Phase 2 and Phase 3 trial. Newly diagnosed more than 3,000 a year. So,
this is a group of patient that will expand year-by-year.
So, what also was a key element last year was the change in guidelines. The
basic come out with a recommendation in the last guideline that if you have
any non-controlled in any of the following symptomatic hypocalcemia
hypophosphatemia, renal insufficiency, hypercalciuria, poor quality of life
with exiting this 95% of the patient, then you should go to PTHs, which gives
me also confident that we will have a strong frontman to get a really optimal
market assessed situation. So, this is our next step. We have still 146 out
of 145, with patients up to three years, pretty impressive. Some of them thus
that was on the placebo treatment.
I will move directly over to one single slide here. I will not go into some
of CNP. If someone doing the Q&A, I can take some of the slide -- now I went
too fast, now we need to go back. I want to say one thing on oncology. We are
working on two unique compound in oncology, a kick starter of the
immunological system, where we use the hydro technology to take it into the
tumor.
The other one is general IL-2 beta or gamma. And you will be tired on looking
and hearing about an IL-2 compound because there have been 25 companies. I
think why does 25 company because people recognize the benefit that it can
provide if it succeeds.
We have moved, brought product to a state, where we have recommended Phase 2
on our TransCon TLR7 by 8 Agonist. We actually have accelerated our IL-2 beta
or gamma much more far than we ever thought about because of the safety and
tolerability. And it's not because we are compromising efficacy. And this is
what I believe, when we come here in the beginning of next year, we will
declare recommended Phase 2 also for our TransCon IL-2 and I really want to
look forward to give you the data that really show how this also is a
(inaudible) product.
So ophthalmology, why did we select ophthalmology? We selected ophthalmology
up from that because we have a TransCon technology platform that basically
can give us product opportunities that no one else can make, make them so
highly differentiated. But because we can have a continuous local release
back in the eyes, not for months, not for two months. I will give you the
curve. When I look on ranibizumab, also known as Lucentis, which both have
been used as a, what we call direct injection, but also in an implant.
We are in a position that we can make and really address the high unmet
medical need that is still in this $10 billion plus sector, because that is
still patient getting blind, cannot comply with the treatment because of the
huge burden. This clinical validated programs, the compound is one it fit
directly our algorithm, like we had in rare disease at endocrinology, where
we expect three out of three.
Going to our data. What we did, this is the best model. For first time thing,
you need to look on the injection volume, 50-microliter, we injected. We can
see, when we inject the 50-microliter, we are in a position that we are
having coverage over the target level, because it's pretty well known what
target level you need to be on always to have sufficient anti-VEGF
neutralization. And we can see we can have it more than 18 months. This
technology platform open up for a lot of product opportunities that basically
could be a pipeline as we have in rare disease endocrinology, but in a much
larger market segment.
Going to our milestones for 2023. If I look on growth hormone and our only
take selected milestone after all the milestones, because you can read the
slides. What I really look forward to is our adult growth hormone data in the
foresiGHt Trial in Q4. The key program, where we will see a major development
next year from commercialization will be our TransCon PTH. We have priority
review, the 13 of April. We are in tense interaction with regulatory
agencies, both in Europe and U.S. We expect still to keep this timeline. This
is a combination product, but it is also building on a lot of proven
technology.
And we expect to launch directly afterwards. We're ready, we're
manufacturing. Everything is built up. The first wave of sales force is
established higher out there. End of the year Q4, we will get a decision from
Europe. Europe, that is still the same high unmet medical need as the only
approved product there will also disappear in '24. CMP, we got what we hope
for in all our data, the four pillar, safety, efficacy, tolerability and
convenience. No doubt, we believe this is the best-in-class product
opportunity. We are enrolling a 2b, which we hope is a pivotal trial. We will
be in a position that we aligning all the patients, because there is a huge
unmet medical need and a huge awareness about what is the profile. So, we
expect that we can enroll the entire trial in four, five months, never
happened before.
Going to the oncology, you can see lot of blue marks because in '23, we
really move into the indication expansion. And we will have the first
analysis, which will continue into '24, where we really hope to prove that we
have a paradigm shift in all our treatment.
Yes, thanks a lot for giving me the opportunity to present today.
Questions And Answers
Jessica Fye:
(Question And Answer)
Jessica Fye:
Great. So we're going to start Q&A here. You can raise your hand and someone
will bring you a mic or you can submit a question electronically, and I can
read it off the iPad upfront, but I'll start.
So, on your ophthalmology vertical, can you talk about how your technology is
differentiated from past efforts to make long-acting drugs for the eye?
Jan Moller Mikkelsen, President and Chief Executive Officer:
So, currently what you're doing is that, if you want to make it longer
acting, you can nearly see going for Lucentis to (Technical Difficulty) you
can also say the Kodiak [ph] approach is to make the molecule larger and
larger, but you still doing a bolus injection. It meaning that you very much
is dependent on how fast back in the eyes, it's clearing the compound. And
when you get older, when you have many of this disease, you have much faster
clearing.
So, what we are doing is basically applying complete paradigm shift, where we
are building particles that sit in hyaluronic acid inside back of the eyes on
a continuous manner day-by-day release an unmodified ranibizumab molecule. By
doing that we total independent on the clearance in back of the eyes. And
when we look on the profile we have, the profile, in my view, is providing
two interesting elements in providing a higher concentration for more than
six months, much, much higher than you really are taking as the target
concentration.
Just look at the half-life 100 days. At the same time, it's extremely
well-tolerated, meaning is that it opened up for many opportunities. It
opened up for an opportunity to have better efficacy, better safety because
of the risk of injection and tolerability, but also not for combination
therapy, because no one can inject in back of the eyes multiple compound on a
twice monthly manner or every third month.
So, it both is an enabling technology, technology for combination product,
but also acts just anti-VEGF treatment as our TransCon ranibizumab, a profile
that never have been seen before, a profile that address one of the key
element of inter-patient variability of clearance. So, it's really is a
paradigm shift.
Ken, do you have?
Kennett Sprogoe, Executive Vice President, Head of Innovation and Research:
Yes. Maybe just a couple of parts. When we talk to retinal specialists, what
they mostly are concerned about is actually not new biology. It's extending
the duration of action, because people -- if you have seen somebody get an
intravitreal injection, you understand, why you don't want to be taking this
on a monthly basis. So, if you can extend it to every six months, you're much
more likely to keep patients on drug and keep them above that critical level
you need for VEGF neutralization. So to me, also this area reminds me a lot
about our rare disease efforts, because also you can't just make the molecule
larger, because it needs to diffuse to the back of the eye.
The retinas at the very back, you have liquid flow that goes towards the
front of the eye and drains whatever you inject into the vitreous. And
there's abundance of literature showing smaller molecules diffuse better to
the back of the eye. So, being able to release a fab, we would expect to have
much better efficacy at the back of the eye and not just neutralizing
whatever is individual compartment.
So to me, the combination of having a modular platform that allows us to take
multiple different compounds together with releasing something that has the
right size. We know size matters, when it comes to tissue distribution and
then being able to treat patients irrespective of vitreal composition,
because we know it thins with age. So, I think those combined makes the
TransCon hydrogel platform extraordinarily well fitted for localized
treatment of vitreal diseases.
Jan Moller Mikkelsen, President and Chief Executive Officer:
As an introduction. This is Kennett Sprogoe. He is our Head of Research and
Development. He was actually one of founding people, when we founded this
company in 2007. So, he really knows the technology platform in and out and
all the benefit we can get it in all the product opportunity. He's basically
the person that designed all our product opportunities.
Jessica Fye:
So, maybe speaking of other product opportunities, there's been a lot of buzz
and I think maybe some anticipation in the market about Ascendis. Ascendis
applying your capabilities to non-rare endocrinology. I think specifically
folks are sort of hoping you'll work on GLP-1 and get into the obesity space.
We obviously didn't hear something on that today. Is that on the table is
something Ascendis might pursue going to kind of more prevalent endocrine
conditions?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I think it's two different discussions. What we had in our Vision 3x3 was to
move out to three different therapeutic areas there from a strategic
perspective. And that is what we did by moving into ophthalmology, because we
really can build up a pipeline in a huge, huge market segment of highly
differentiated product that really will be best-in-class, really addressing
some real unmet medical need. We are in rare disease endocrinology. And if we
go outside and remove rare, for me, it's just something I would do and not
really discuss it before this competitive environment that is that before I
have data, not waiting to say 18 months before we move into clinical
development or anything like that.
It's a highly competitive area, I'm here to win. I'm not here to give any
advancement to any competitor. If we do it, we will do it. If we feel that
somebody is fitting our pipeline, it's fitting the benefit of the patient,
it's fitting the benefit of value creation, we will do it.
Jessica Fye:
We got a question in my e-mail about PTH and maybe I'll wrap it in with
another question that I was going to ask on the product. So, you're starting
this expanded access to help patients initiate on TransCon PTH prior to the
approval. And presumably, that's create a favorable launch dynamic, where
you'll then be able to convert them over.
So, first question is, how do we think about the timing over which
reimbursement for TransCon PTH could ramp up? Should that look different than
TransCon Growth Hormone did?
And second, this is the investor question, what's a good assumption for
TransCon PTH price is not part of -- the right range to think about?
Jan Moller Mikkelsen, President and Chief Executive Officer:
Yes. Let me take the first one, because I think what we did in launch of
SKYTROFA. We had in the war-room, we want to a lot of different strategies,
how do we want to launch SKYTROFA in the U.S. We cannot go the rebate way,
giving a lot of revenue in the beginning, but less profit.
We decided to build on the strength of the product, because we have the
best-in-class product that is highly differentiated to every daily growth
hormone, but also other long acting. So, we took the long term, long staying
to an established market. We didn't go to the classical way to basically
provide a lot of rebate. We went to the medical exemption pathway, because we
didn't accept that the rebate that was given to us.
How can we do it and why we can do it extremely successful, it's because we
have the best-in-class product opportunity that really make a meaningful
differentiation for the patient. So, both our physician and everyone is
willing to take the work to get the medical exemption, because it's really
benefited.
TransCon PTH is completely different. We are launching into a segment, where
the only opportunity that was there is taken away from the market. We are
launching into an air, where there is basic no competition. There is a huge
recognization of the unmet medical need, there is a huge recognization of the
benefit we can provide to the patient, which I think is supported by two
things and I call it validation, the guidelines.
I have never been in a position, never been in a position that basically
before you launch the problem, there is a guideline that's saying that you
should utilize this product for most patients. First time guidelines is
something that come one or two years after launch. The other thing is also
being recognized at least from my perspective, is as recognized to the
regulatory agencies by providing us a priority review, providing us the way
of making an expanded program for the patient before we basically can launch
the product really to help the patient.
Yes. Now I forgot the second question.
Jessica Fye:
Price?
Jan Moller Mikkelsen, President and Chief Executive Officer:
Price is something we decide when we -- just before we launch. We're doing a
lot of analysis related to price today. We actually are not compares to
NATPARA. We are thinking about these product opportunities out from a
complete different label that was giving to NATPARA. We are positioned this
product from the benefit we're providing to the patient. And this is how we
think the price structure.
Jessica Fye:
Questions on that? I think consensus is on saying like the $40 million, maybe
$50 million range for TransCon PTH for 2023. Is that a number that you're
comfortable with thinking about the initial the launch ramp?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I think that's always, I like to see and be quite sure, when I come up with
an algorithm. I like all this to come up with algorithm because I'm
mathematic. So, from my perspective is when we come into the launch, when
we're coming in and seeing what we are, I think it's a good timing to give
you some kind of guidance on it.
But just think about it there is 5,000 patients that were used to use PTHs,
5,000 patients in the U.S. People that have experience with using PTH, where
the drug got taken for them. Then you have where we basically recruited in
our Phase 2 and Phase 3, the 80,000 patients, where we now have all of them
basically staying, staying, staying on treatment. What did that tell me? It
tells me all patients will benefit for this treatment. That I think is the
key element.
Jessica Fye:
I think for TransCon CNP, you've talked about filing in the back half of 2024
on the back of your Phase 2b trial. Have you talked to the FDA and confirmed
that they're good with your endpoint and trial design stuff like that?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I think the end point is really well recognized, analyzed growth velocity.
And we're actually doing a simple form of analyzed growth velocity, which is
also recognized by FDA and other regulatory agencies that we're not making a
difference between pretreatment, but just looking on the absolute analyzed
growth velocity. So, the endpoint is pretty, pretty simple.
Our aspiration is not have a labeling on linear growth. Our aspiration is to
have a treatment of achondroplasia and also address the comorbidities. This
is why -- one of the things that's struggling me, we have now accomplished
trial with patients more than two years. What is our retention in our study,
100%, 100% of 57 patients? What are we providing to this patient group that
is not recognized in analyzed growth velocity, because I don't believe that
everyone just believe that getting height is the important thing of
achondroplasia. At least this is my understanding when I talk with parents
and listen to some of the patient group.
What are we giving to them? And that is what we want to qualify in our
pivotal 2b study. So, we can ensure that we also can have that part of our
labeling discussion. And I think that is the key element of what we're doing.
It's pretty clear. No one has any questions.
Jessica Fye:
You talked about SKYTROFA and the nice kind of trajectory that's starting to
emerge there. But I think you could have another long-acting competitor
coming to market as well. How do you think about that competitive dynamic
once you're not the only kind of long-acting growth hormone?
Jan Moller Mikkelsen, President and Chief Executive Officer:
I could think and when we look on the data that is under other long-acting
product and then compared to daily growth hormone. On an absolute level, when
you look on outcome related to a low European dose that could much lower,
just hitting statistic non-inferior on an absolute low. When we go to body
composition, the Phase 3, the basic proof that only have the half of the
activity compared to daily growth hormone.
When I see our SKYTROFA, we're highly differentiated, best-in-class, we had
an analyzed growth velocity that was a statistic higher than the one we got
from daily growth group. We hope we can show the same thing in body
composition.
And this is why I'm not really believing it's changing anything, because we
basically will be in the best-in-class product opportunity potentially would
change a little bit how much that is left of daily growth hormone. It's not
changing any of our basic forecast.
Jessica Fye:
Great. Well, we're about out of time, so I'll leave it there. Thank you.
Jan Moller Mikkelsen, President and Chief Executive Officer:
Thank you so much.
