May 5, 2025 • 55 mins
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On today's episode, Tolga Tanguler, EVP and Chief Commercial Officer at Alnylam Pharmaceuticals, talks about commercializing RNAi therapies, how they fit into health insurance reimbursement systems, the company's use of value-based contracts, and building therapeutic franchise "skyscrapers." Tangular also shares his thoughts on commercializing RNAi therapies for larger patient populations, compared with rare disease populations, and reflects on changes in the biopharmaceutical sales and promotion model.
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Episode Transcript
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Ben Comer (00:00):
This episode of the Business of Biotech is brought
to you by Avantor.
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(00:44):
Welcome back to the Business ofBiotech.
I'm your host, Ben Comer, chiefeditor at Life Science Leader,
and I'm pleased to speak todaywith Tolga Tanguler, Executive
Vice President and ChiefCommercial Officer at Alnylam
Pharmaceuticals, an innovator inthe RNA interference or RNAi,
therapeutic space.
Tolga is a commercial leaderwith deep industry experience
(01:08):
who has helped commercializesome blockbuster brands you may
have heard of, such as Viagraand Eliquis.
He also led Pfizer's raredisease group for North America
before joining AlexionPharmaceuticals as senior vice
president and head of Alexion'sU.
S.
organization.
Tolga joined Alnylam in 2020and has been a key player in
(01:32):
expanding the company'sfootprint globally to more than
60 markets and dramaticallyincreasing patient access to
Alnylam's therapies.
Thanks for being here today,Tolga.
Tolga Tangular (01:39):
Great to see you , Ben.
Thank you for having me.
Ben Comer (01:42):
Absolutely.
I wanted to start with how yougot into this line of work.
What attracted you initially topharmaceutical drug marketing
and commercialization?
Tolga Tangular (01:53):
Yeah, thank you Ben, and I wish I could tell you
that there was this great,great grand plan for me to join
the industry, but it came a bitof, I think, a happenstance, and
I feel very fortunate to bepart of the industry, looking
back after 25, 30 years.
Essentially, my family is a goodmix of a business executive and
(02:17):
my mom is a psychologist whohas been in the medical industry
, so medicine was not a newterritory for me.
While I was at business school,I had a number of offers, one
of which was actually an offerfrom Merck that was part of the
(02:38):
leadership development program,which really fit very nicely
with something that my fatheralways used to say, which is, if
you want to do something and ifyou want to lead something,
learn from the bottom andunderstand how actually the
sausage is being made.
So Merck Leadership Program wasactually a great opportunity
and that's why I actually pickedit.
And, of course, again, science,medicine, technology were in
(03:01):
areas that were too unfamiliarfor me.
So that was actually a greatstart.
And again, I've been veryfortunate being associated with
great companies like Pfizer,Merck in the beginning, Pfizer
throughout my formative career,and then, as you mentioned, I
had the opportunity to join thebiotech world, first with
(03:22):
Alexion and now last four orfive years with Alnylam, which
has been just a phenomenal ride.
Ben Comer (03:29):
Yeah, you went from gigantic drugs to rare drugs and
now you know Alnylam might beheading back.
The pendulum may be swingingback towards some larger patient
audiences.
I have to ask you about workingon Viagra.
What was that experience like?
Was that the first big brandthat you worked on?
Tolga Tangular (03:49):
It was.
And, frankly, what's reallyinteresting, I was given an
opportunity to work either withCelebrex or Viagra and I made
the decision early on that Iwould actually work on Viagra.
A what an iconic brand, and whowouldn't like to kind of learn
and understand how an iconicbrand works?
And the second piece of it was,unlike most of our medicines in
(04:14):
those erectile dysfunctioncategory, doctors tend to
abdicate the sort of writingthese products to their patients
.
So I felt like I'm going towork with science and I'm going
to work with these very uniquetherapies throughout my career.
But Viagra will probably comeonce in a lifetime where you
actually get to understand howpatients think through, and it's
(04:38):
obviously in those daysespecially.
It was a stigmatic category andworking in a stigmatic category
and working in a stigmaticdisease area and working with
the patients was very intriguingto me and, frankly, I never
looked back after the experience.
It really allowed me tounderstand how patients think
and how to actually helppatients with a condition that
(05:02):
is so stigmatic.
Ben Comer (05:04):
Yeah, absolutely.
In the late 90s I was workingin a mom and pop pharmacy is
actually a compounding pharmacyand I remember the Viagra sales
team coming in, which maybe youcan answer this question for me
before I tell this short story,I promise.
Tolga Tangular (05:22):
I want to talk more on biotech, but yes, let's
talk about Viagra.
Ben Comer (05:26):
Yeah, just for a second.
Tolga Tangular (05:27):
Bear with me here.
Ben Comer (05:28):
I was always curious about why the sales detail team
came into a pharmacy, given thatthe pharmacists weren't writing
prescriptions.
Can you clear that up for me?
Tolga Tangular (05:38):
Yes, yes, actually.
In fact, when I was a year,when I started my rotation
program at Merck, I spent in thefield a year and we were asked
to go into these pharmacies.
It was mainly because youwanted to understand how the
pharmacists reacting to thepatient needs and also
(05:58):
understand if they see anydemand, so we would actually
just talk.
It was always a bit of anoptional call in those days.
I don't think we do thatanymore as an industry and you
have, you know, ability tocapture a lot of data and
insights through third partywithout going to these
pharmacies, but it was actuallya bit of an industry standard in
the 90s.
(06:18):
You're spot on.
Ben Comer (06:19):
Yeah, well, what I remember from the sales detail
folks that came through was aViagra calculator that you may
remember this.
It was flat and you pushed abutton on it and the top kind of
rotated around and thenultimately stood the calculator
up a little bit, which we were,you know, as a high school male,
I was very, very tickled by.
Tolga Tangular (06:40):
But anyway, well , listen, those are some of the
practices that I'm so glad thatthe industry moved away from.
Ben Comer (06:46):
Well, I was going to use that as a segue to ask you
you know how launching andcommercializing new therapies
has changed since you worked onon Viagra in the early aughts.
Tolga Tangular (06:57):
Yeah, I mean listen, like everything, the
industry had some growing up todo and I think we did.
And obviously the diseases thatI'm so keen on commercializing,
(07:19):
which is simply a word meaninghow do we get this product value
back to our companies thatcontinue to innovate for
transformative diseases thatpatients that need the most?
So that's been my passion andthat's how we've evolved, and
what I really like about thespace that we're in has a lot to
(07:41):
do with the words that I justused, which is high medical
needs and transformativetherapies, and society right now
, in the right way, startvaluing and rewarding those
actually products that trulymake a difference, so that you
know you don't get to work on,spend a lot of human and capital
(08:03):
to areas where you're justdeveloping a me-too product that
is no longer acceptable andthat's not where you generate
value.
And let me tell you alsoanother personal story about why
I'm so keen on actually workingon those products.
It has a lot to do with my sonand his journey.
(08:24):
Products has a lot to do withmy son and his journey In about
the middle of my career this isjust before I start leading the
rare disease unit in NorthAmerica for Pfizer.
My son was diagnosed withleukemia childhood leukemia.
He was 11 years of age and eventhough, you know, I was in the
(08:44):
middle of my career in thepharmaceutical biotech industry
and I always thought I was verypatient focused and I always
cared about the impact that ourmedicines, or potential
medicines, will make on people.
But, boy, when that hits you inyour family in a very personal
way, you start looking at thingsvery differently.
(09:07):
And, frankly, that was one ofthe reasons why I was attracted
to Rare, because you knew thatthe impact that individual
impact you can make is reallyprofound on a single life.
And now, obviously, with thetherapy areas that we're working
on at Alnylam for the future,is what really excites me is you
(09:29):
can actually make thoseprofound impact in a much
broader population.
And what's so great aboutAlnylam is and I guess we'll get
into this is the technologyplatform that we have that
enables us to do, whether it's asingle genetic mutation
condition or a protein that mayactually impact a significant
(09:50):
illness like hypertension orhypercholesterolemia.
Ben Comer (09:54):
Yeah well, thanks for sharing that story.
Did your son survive?
Tolga Tangular (09:57):
He did I should have said that, yes, he's an
annoying 20-year-old collegestudent.
He's doing great, and we allrecognize that none of those
things are for granted.
Ben Comer (10:09):
Yeah, yeah.
Well, I'm happy to hear that Iwanted yeah.
Tolga Tangular (10:14):
And, by the way, I mean, let me add this he
wouldn't have survived if itwasn't for our industry and
science, because only 50 yearsago this was a death sentence.
Now the prognosis rates are asgood as 90%.
So that's the progress that weneed to continue to make,
because there are a lot of kidsout there, there are a lot of
adults out there whose illnessesare not transformed yet, but we
(10:40):
were very lucky that we gotinto that bucket of diseases
that science and medicine havefigured out a way to solve it.
Ben Comer (10:50):
What would you say is different about launching and
commercializing an RNAi drugversus other more established
drug modalities?
And I'm thinking you know wehad a short call just to prepare
for this podcast Tolga, and youknow one of the things that
(11:26):
that came up was this kind ofyou know, I don't know if drug,
but also how you bring such anew modality to physicians and
overcome, you know, some ofthose kinds of resistance to
change that they might present.
Tolga Tangular (11:41):
Right, yeah.
So I mean, listen, I find it,to be honest, is an opportunity.
I think we talked about Eliquisand, how you know, at the time
we had head-to-head data, bothon the primary endpoints, like
you know stroke prevention andrisk reduction, and safety
(12:03):
versus Coumadin, which is a50-year-old product that's been
out there for blood thinning,and essentially, even though you
had a head-to-head trial thatshowed superiority versus
Coumadin, in both on primaryendpoints as well as on safety,
(12:23):
doctors were not willing to makethe change.
They all felt, like you know,they were able to control the
patient's bleeding, which wasnot an easy dosing, and then you
had to get liver enzyme testsand everything, and that took us
a while.
So there is, I guess, aninherent condition in all of us,
and also with doctors, to be alittle skeptical about new
(12:45):
treatment options.
What's so great about, I think,what Alnylam provides and
allows us to rethink is the factthat you can literally do a
subcutaneous injection everythree months to, you know,
lessen the hypercholesterolemia.
(13:05):
One of our products is rightnow being marketed by Novartis.
It's a product named Leqvio.
So that is.
You know, I see that thenumbers are picking up.
That is exactly the examplewhere how doctors tend to resist
.
Now I find that also gives us anopportunity to completely
(13:27):
rethink how medicine ispracticed.
We're currently working on aproduct called Zilebesiran that
is subcutaneous in the injectionevery six months that lowers
potentially lowers systolicblood pressure.
Now we have several highlyeffective medicines that are out
(13:48):
there that lowers bloodpressure and they are
inexpensive.
Yet, for any account, there isabout 20 million Americans that
suffer uncontrolled bloodpressure that results in stroke
and other significantconsequences of blood pressure.
So why is that?
Well, one of the answers isactually probably patients are
(14:11):
not taking their medicines everyday.
Once a day pill or twice a daypill, as sound, as simple as it
is.
Now I'm that age where I'mtaking some of those medicines.
I can tell you I miss them andI know what the consequences are
.
So bringing a medicine that ishighly effective and safe and
(14:31):
with a simple subcutaneousinjection that you visit your
doctor or a nurse comes in yourhome and injects you, opens up a
whole set of opportunities.
That really excites me, becausecommercializing a new
technology in that respect isreally, really, I think,
advantageous.
But it's going to require us toalso challenge ourselves to see
(14:54):
how we actually bring some ofthose opportunities in mind.
Now, the other plus I thinkthat we have that maybe amazing
gene therapies, therapy optionsare actually struggling is we're
not one and done.
You know, we're not actuallyrequired to change how we get
(15:17):
reimbursed.
Actually, we fit nicely intothe reimbursement structure that
is currently set for medicinesthat are taken regularly.
We don't need to actually priceour disease as one and done,
which actually gives us someadvantages to actually work
within the existingreimbursement system.
And those are, I would say,actually it's not going to
(15:39):
require us to change.
But at the same time, thesetreatment regimens that are
actually infrequent and simple,with a subcutaneous injection,
may give us sort of anopportunity to force the health
care system to rethink howmedicine is practiced.
Ben Comer (16:00):
You know.
That brings to mind for me, youknow, a key commercial issue
that I wonder if you know I'msure some of our listeners for
the business of biotech willknow about this Others may not
though which is the gross to netissue.
And I noticed in fourthquarter and 2024 earnings report
(16:22):
that there were some positivegross to net adjustments made in
the US during the fourthquarter, and I wonder, Tolga,
would you mind just giving abrief, very high level
explanation of what gross to netis?
Tolga Tangular (16:37):
Yeah, essentially it's the the your
products revenue minus, you know, minus essentially your
royalties and rebates and costof goods.
So that's how you know grossnet is adjusted.
And look, I mean, I think it'sa it's a question of for a
(17:00):
company that is destined to tochange how medicine is practiced
.
We need to continue to forceourselves and our organization,
how our cost of goods isactually continuing to be
brought down.
And this is an area whereobviously we're not a biologic,
(17:23):
we're also not a small molecule.
Our manufacturing is complexand it's not cheap, but we
certainly believe, unlike a genetherapy cost or even a biologic
cost, we have an opportunity toactually to continue to further
reduce cost.
Our CEO to continue to furtherreduce costs.
(17:43):
Our CEO, Yvonne Greenstreet,has this vision of democratizing
RNAi, meaning try tomanufacture it as inexpensively
as possible so we can actuallymake it available not just in
the US but in other marketswhere cost is even a more bigger
sensitivity.
We're trying to obviously makethat happen.
(18:04):
Now, specific to the Q4 resultsthere's always going to be ins
and outs how those rebates areactualized.
There's some also timing ofsome of those rebates, how
they're actually beingrecognized.
So I wouldn't necessarily paytoo much attention to quarterly
(18:25):
changes.
What's really helpful is tolook at the annual metrics, and
those obviously metrics willalso continue to evolve.
Ben Comer (18:34):
Right and just for the benefit of our listeners
gross to net.
Gross obviously meaning whatthe product is sold for.
Net is what you're actuallymaking on the product and a lot
of times the criticism of thisso-called gross to net bubble
has to do with rebates.
Now, Tolga, you're reducing thecost of goods, so that's an
excellent way to improve grossto net and, similarly, fixing
(18:58):
the compliance issue, which I'vebeen a journalist covering
biopharmaceuticals for close to15 years and for a while there
it seemed like once a year I'dwrite the adherence and
compliance article and somebodyhad a new idea about how to
improve it.
It never improved.
You know we still.
It's an ongoing challenge, butyou know, when you have a shot
(19:19):
that you can give over a courseof months, you're, you're taking
yourself out of that compliancequandary.
Similarly, with lowering thecost of goods, you're setting
yourself up for success in grossto net, at least in terms of
things you can manage.
Tolga Tangular (19:38):
No, you're spot on, Ben, because I mean, look,
just like you.
Over the years when I worked onespecially on tablets, both the
industry as well as likepharmacists I've seen
pharmacists actually have thesedevices that every time you open
the pill tab it would actuallysend a message whether you're
(19:59):
compliant or not.
So the whole industry has beenworking around this issue,
around tablets, and we haven'tfound anything, because I think
inherently, taking a pill everyday or twice a day is not a
normal human condition.
Now again, there are people whoare incredibly adherent.
But even in oncology we seeadherence rates as low as 70
(20:20):
percent I mean this is cancer.
Rates as low as 70% I mean thisis cancer In more you know,
sort of metabolic diseases wesee rates at 60%, 70%.
So if we can actually solvethis by simply how patients take
their medicine every threemonths, every six months in
physician office or a nursepractitioner visiting your home,
(20:42):
I think we will go a long way.
And I don't think we actuallywe can't overestimate the human
health impact that's going to bemade on the patients.
And if you look at our currentproducts, our adherence rates
are 90, 95% every category thatwe work on.
So there's something obviouslyto be said about how our
(21:06):
medicines are administered.
Ben Comer (21:08):
Yeah, I mean.
The other thing about a dailytablet and compliance to me is,
you know, particularly maybe indisease areas like cholesterol
or even diabetes.
I think one of the majorchallenges is that if you miss a
dose, nothing really happens.
There's no consequence rightaway from missing a dose.
(21:29):
It's taking it over a period oftime and missing doses, and so
when you're not automaticallyfeeling better because you took
your cholesterol medicine on agiven day, it makes it difficult
to really incentivize.
Tolga Tangular (21:45):
You're spot on, and as an industry, I think we
face two major hurdles.
One is the physiciancomplacency, because if you can
do this yourself, or thosecolleagues that are watching
this, should do that.
If you ask any doctor in anytherapy area whether their
patients are actually adherentor compliant, they'll say yes.
Ben Comer (22:10):
Of course right.
Tolga Tangular (22:12):
So there is that , I think, issue.
And then, to your point,patients, yeah, if I miss my
statin or hypertension, butagain I'm giving you some
numbers, even in cancer, wherepatients actually don't take
their medicine, or maybe theyneed a caregiver that needs to
do that and they don't have thesocioeconomic, you know, setup
(22:32):
to be able to do that.
And we see it mostly onpediatric patients.
And if the caregiver is, youknow, less educated or a single
parent that's working, thosecompliance rates tend to go down
.
So this is an area where Ithink we need to continue to
work as an industry, and onesolution is obviously come up
with better medicines that aretaken less frequently.
Ben Comer (22:57):
I mentioned in the intro Tolga about Alnylam's
global expansion.
Almost half of the company'srevenues now are coming from
ex-US markets.
What can you say about thestrategy that Alnylam followed
to accomplish this and what aresome of the biggest challenges
(23:17):
in building a large and growingglobal footprint?
Tolga Tangular (23:22):
Yeah, I mean, first and foremost, I don't
think I can take the full creditof the online expansion
strategy, because those actuallywho founded the company always
had this really bold vision and,frankly, since I've arrived in
four or five years ago, whatI've been able to do is to
(23:42):
actually embolden that strategyeven further.
Now to your point.
We do generate about 40% 45% ofour revenue.
We continue to grow in terms ofvolume about the same rate that
you would see in the US and,frankly, it's mainly driven by
(24:02):
how I believe we're approachingour expansion.
And for a small biotech, Ithink we're punching way above
our weight and I don't think weever look back about having that
international presence.
But we do it very thoughtfullyand very carefully because
actually it can put a strain onyour resources.
Having that geographicfootprint, put a strain on your
(24:27):
resources having that geographicfootprint, but the potential
benefit of investing a littlebit on your ex-US markets
actually happens, that youactually balance your revenue
flow.
So that's actually a big plus.
You start finding opportunitieswhere there might be some
endemic regions that are less inthe US.
We certainly see that in ourultra-rare disease area and as
(24:49):
you grow you don't need to leavea lot of value on the table for
a third party or distributorthat actually ends up actually
really commercializing yourproduct, where you get to keep
that value again to transfer itinto your research and
development.
You get to keep that valueagain to transfer it into your
research and development.
(25:11):
So, with that outlook, what wedid is we started looking at the
globe not just geographically,but actually we looked at it
from an archetype market,archetype perspective.
And what do I mean by that is,if I look at geographies like
Europe, there are actually many,many archetypes within that
European geographies like Europe.
There are actually many, manyarchetypes within that European
geographies.
You have developed markets likeUK, Germany, Spain, Italy,
(25:32):
where there's value that's beinggenerated by good reimbursement
system, good healthcare system,where you have access to new,
innovative therapies.
But you also have markets whereI don't know Turkey, Greece.
You know Eastern Europeanmarkets where access to medicine
is less likely and where youdon't want to probably spend a
(25:54):
lot of time and energy incommercializing and have someone
else do it, because the juiceis not simply enough, the
squeeze.
Now, when I look at SoutheastAsia, I see more similar markets
like the ones that I justdescribed with you, like the
distributor markets like Vietnamand Korea and Singapore, where
(26:16):
you actually, again, you maywant to go to a distributor and
not have your own directfootprint.
But then you have Japan, thatactually very similar markets,
like Germany and UK and Spain.
So what we did is we said let'slook at the market archetypes,
let's combine those markets thatare similar under one roof and
(26:39):
that's our international marketthat actually spans through
Canada all the way to Japan,including all major European
markets.
And then, when it comes tothose distributor markets and we
call them affectionately ourpartner in emerging markets
let's consolidate with few.
So, instead of having work withlike 10, 12 different
(27:01):
distributors, let's keep them afew, two or three of them, so we
can actually expand throughthem.
That actually helps us toactually minimize disruption,
deepens our relationships and,by the way, it allows us to make
them more compliant.
We actually have these partneremerging markets that we work
(27:23):
with a few of them and we expandthrough them, and then we
obviously treat our US as oursingle most important market.
And then the rest of the worldwe call them partner and
emerging markets.
Now, the other category we haveis our global rare business
units.
So, unlike our TTR franchise,where we really focus on
(27:46):
market-by-market opportunity,our ultra-rare market, we
actually consolidate our expensebasis in a very small footprint
and our global rare franchiseoperates as an end-to-end
business unit and that actuallygives us a lot of efficiencies
and also allows us to focus on.
Not all markets in ultra-rareare equal.
(28:08):
So our global rarity maybefocus more on Middle East
markets where we see endemic onhyperoxaluria, but then we don't
go and maybe work too deeply onFrance for instance, because
the opportunity may not be asbig as some of the markets in
the Middle East.
Ben Comer (28:28):
Yeah, that makes a lot of sense.
I'm curious about what factorsyou consider when you're
deciding whether or not topartner with a distributor or go
as Alnylam.
How do you make that call?
Tolga Tangular (28:43):
That's a great question.
First of all, it's a verynuanced call and there's no one
single playbook.
But what we look at, of coursethe longevity and the growth
trajectory of the particularcategory For any particular time
point.
We say, look, do we have theresources right now Because
we're just about to becomeprofitable this year?
(29:05):
Right, that's what we declared.
So we still need to look at oursales and administrative costs.
We look at, then, thecomplexity of the market Are we
going to be able to actuallybuild the regulatory muscles
that we need to have?
And again, if the longevity,the sustainability of that
(29:26):
growth, is worthwhile, then wego after it.
I'll give you one example.
Actually, it's interestinglyoriginally Australia was a
market where we said it's partof this sort of archetype where
it needs to be under ourinternational market, because
you have socialized medicine,you have access to patients and
(29:48):
it's reimbursed.
So we said let's go and workand have our footprint.
Then, actually, our partner inthe emerging markets, lider,
gave us a challenge.
He said I can actually makethis product available faster
and I can actually do it with alower cost base.
So both teams got together andactually we ran a business
(30:10):
simulation and we ended upactually saying you know what?
For now, let's actually go anddistribute this market with a
trusted partner that we alreadyknew, and you know what?
They beat those timelines andwe actually made one of our
products available already inAustralia much faster than we
would ever imagine if we were togo there faster.
So, as I'm explaining, there isno real one single playbook.
(30:34):
There are principles that welook into and then we make the
decision accordingly.
Ben Comer (30:39):
That's really interesting.
Who is the partner in Australia?
Tolga Tangular (30:44):
It's a company called Medison which we actually
partner with multiple markets.
Ben Comer (30:52):
Great.
What role, Tolga, does pricingplay in mapping out market
entrance strategy globally?
I mean, do you think aboutcountry sequencing and price?
How do you think about that?
Tolga Tangular (31:05):
Yeah, first of all, I mean, of course, to your
point, it's a bit of an industrystandard to make sure that we
actually really understand andappreciate cross-border impact
of how it's priced and also ifwe were to sort of be dealing
(31:25):
with reference price impact andso forth.
But I think what's reallyexciting about Alnylam and again
this is an area where I like tothink that we've been punching
above our weight is, before weeven commercialized our first
product, we came up with apatient access philosophy and
that patient access philosophyhas been actually sort of the
guiding light for us.
(31:46):
We're never going to increaseour price above inflation and if
you look at our pricing overthe years now we have been
commercializing products for thelast five, six years we made
very few price increases, ifthat ever, and that's always
been under inflation.
So that's been number one.
Number two is we play to ourstrength of our science and our
(32:12):
platform technology.
We only promote and make ourproducts available that are
transformative as medicines.
So we're, essence we alwayskeen on what's the value to the
society.
How am I going to actuallyinterpret that for the payer?
Then, the last but not least,what's the patient affordability
(32:34):
is going to be?
It's one thing to put your listprice and to your point.
In the US we also have thisrebates that we need to work
with.
It's an imperfect system.
We don't like it, but that'sthe system that we're currently
working on.
And then it becomes thisquestion about what's the impact
(32:55):
on the patient.
Is the patient going toactually have to pay the copay?
Are there programs that we canmake that happen?
Are there things that we canwork with the payers?
We have been pioneeringvalue-based agreements.
Now those value-based agreementsare essentially about really
putting your money where yourmouth is.
(33:16):
So if I'm negotiating with apayer and saying, look, we
believe the patients will stayon therapy and they're not going
to have to deal with theconsequences of the disease,
albeit maybe organ transplant orpatient, if they stay on
therapy, they're not going to behospitalized.
Depending on the label,depending on the agreements, I
can't disclose a lot of those,but what I can tell you is we're
(33:40):
now covering about 60 percentof those patients that are
covered under commercial orMedicare advantage through these
value-based agreements roughlyabout 55% of those.
So those really actually helpus.
So it's not just the cost orthe price, it's how do you
actually build the ecosystemaround that that enables us to
(34:01):
actually go in and provide thevalue narrative around the
payers.
Ben Comer (34:08):
Yeah, I want to get into this value-based contracts
topic a little bit.
It's something I probably firstwrote about, this idea of
value-based contracts, I don'tknow 10 or 12 years ago and it's
kind of gone up and down interms of interest and popularity
and value-based contracts.
I think, like so many things,there was great excitement at
(34:31):
the beginning and then some kindof reality seeped in where
people found out it's.
You know it's not so easyalways to manage these kinds of
contracts, assess them.
You know across sort of agreedupon points and you know the the
lifestyle, life cycle of themedicine or even in the
patient's health.
Could you, would it be possible, tolga, to give us an example
(34:53):
or two of a value-based contractthat Alnylam is involved with,
sort of from soup to nuts.
Explain you know what productsinvolved, how it works.
Soup to nuts.
Explain you know what productsinvolved, how it works, how you
assess it, how it's managed.
Tolga Tangular (35:06):
Right.
So just up front, you know I'llbe able to give you some flavor
, but not all the all thespecifics, but I'm sure it's
going to be helpful for youraudience.
But look, I mean, let's, let'salso take the first point you
just made.
Um, you have to stick with it,right?
So one of the great, I think,skills, or the values that we
(35:31):
have as Alnylam, is being veryresilient.
So when RNAi was in favor, wewere there and RNAi wasn't in
favor, a lot of these big pharmacompanies pulled out we were
still there.
And value-based agreement is abit like that too.
If you believe in the theoryand if you believe in the
practice, working with somepartners, in the long term it
(35:57):
actually gives you credibility.
You also learn from each otherand you start building this as a
real capability.
So you can't just treat this asa flavor of the month, and
because of that, I think I cankind of safely talk to you about
some of the programs we have.
So you want me to be a littlespecific.
(36:17):
So let me give you a fewexamples, one of which is in
ultra-rare, ultra-rare.
So in ultra-rare, what youusually see is, especially in
the United States, per treatmentcost tends to be higher than
(36:40):
your other treatments andtherefore payers avoid sort of
end up with these patients.
But if you're around there andif you're covering many lives,
you're going to end up with somepatients.
Unfortunately, frankly, not allthese rare conditions, a very
small percentage of these rareconditions, are actually now
diagnosed and treated.
But when you get them, what youworry is how am I going to
(37:03):
manage this cost inflation andis this going to be impacting my
level of predictability?
And, as you know, insurers careabout the cost but they care
more about predictability.
So one of the things we didwith the value-based agreements
is we said look, according toeverything that we see and the
(37:24):
prevalence numbers that we seein ultra-rare, we're going to
cap some of the costs if anumber goes way above what that
prevalence ratio should show,based on all the population and
epidemiology data that we have.
Ben Comer (37:43):
So that provides yeah , you're giving them some
predictability, exactly.
Tolga Tangular (37:47):
So that's one angle.
Another angle that we do withour TTR franchise is we look at
clinical outcomes.
We say, look, according to this, here's how the patient should
behave, and if you don't, thenwe're actually willing to
provide you a certain rebate ora discount or refund based on
(38:09):
the given, the value-basedagreement.
So by doing this again, we Aprovide.
Frankly, it also shows ourconfidence about look, our
medicines are based on geneticinformation, based on the
biology, human biology, so itgives us a lot of predictability
and confidence that ourproduct's going to work.
And now we're just about tofinalize our CV outcomes study
(38:36):
on our cardiomyopathy, thelabeling I should say we just
published the Heliospeed.
So we know these products work,we know that actually it
provides a real benefit to thepatient.
So why not actually tell thepayer that we stand behind those
data points?
(38:56):
And that again gives us anenough.
Is every payer willing to do it?
No, because, to your point, noteverybody is equipped to do the
administration of how to followup these patients.
They say, ah, by the time ittakes me to actually follow up
the patient and administer this,it's going to get more costly.
But in some cases we simplifythe administration and in most
(39:22):
cases we do, so that actuallyworks really well.
And then some payers believe inthis and they like what they
see and they stick with us.
Some payers don't prefer it,and that's OK.
Ben Comer (39:32):
So you're working directly with the insurers to
help set up this, this wholeprogram of how they can manage
results.
Do you find?
I mean, does it work betterwith insurers?
Tolga Tangular (39:42):
Some governments , by the way, sort of interrupt
you, but in some cases we dowork ex-US with some governments
.
Ben Comer (39:48):
With governments as well, right?
Do you look for health insurersor governments who have some
experience in these kinds ofdeals, or are you also building
some of you know forging thesefor the first time with some
health insurers?
Tolga Tangular (40:02):
It's a little bit both.
Frankly, those who have startedthe journey five, six years ago
with us, they like what theysee, so they stick with us and
in some cases we publish andshow them hey look, this is what
your competitor is doing.
Wouldn't you like to be part ofthis?
And especially those plans thatlook at the totality of the
(40:24):
patients, that are wellintegrated networks.
They really like this.
So they not only have theinsurance system, but they also
they cover the patient at thepayer side and also provider
side, so they actually fund theyou know, the hospitals, those
systems.
They really like that those,those systems.
Ben Comer (40:50):
They really like that , right?
Yeah, um, I wanted to um moveon to alnylam, you know, kind of
crossing back over into intolarger therapeutic indications.
But before we leave raredisease, I wanted to ask you
about diagnosis, which is acritical aspect of rare disease.
Getting the right diagnosiscritical.
I'm wondering, uh, what alnylamdoes, what kind of work Alnylam
does in terms of helpingpatients get diagnosed?
(41:11):
What can you tell me about that?
Tolga Tangular (41:13):
So that's your spot on.
The ultimate test is once youmake the product available.
We immediately see, first ofall, a pool of patients that
were already diagnosed and theyare desperately looking for an
option and we go and make surethat you treat that.
But then you need to actuallycontinue the pool of patients,
(41:35):
the flow of patients that arecoming in down the pike, and get
them treated early.
So making the product availableis actually a big leap forward
in itself because it increasesawareness.
The second point is we alsowork with you know diagnostic
companies.
If it's a hereditary disorder,we work with you know genetic
(41:59):
counselors, actually geneticdiagnostic companies that
provide genetic testing andassays available for the
providers.
So it's essentially reallybecomes a question of where is
the problem?
Is it really about sort ofgenetic testing?
(42:21):
Genetic testing Is it reallyabout awareness or is it
actually really?
improving the non-invasive waysto diagnose the patient.
In one instance, for instance,in TTR, we've been fortunate
enough to have scintigraphy.
Essentially, it's an imagingtool that is widely available in
(42:48):
the US, but you can actuallymake it multi-purpose and by
taking a different dye you'reessentially having the
accumulation of amyloidosis inyour body light up.
It wasn't invented for that.
Now one of the institutionsthat we work very closely
figured out that it can be usedfor that purpose.
(43:09):
So how do you actually makethat available?
How do you actually disseminatethat information?
So it's really a question ofunderstanding the value chain
where they actually you getstuck in patient diagnosis and
start identifying that andworking with the ecosystem.
Ben Comer (43:25):
Excellent, that's great.
Getting back to largerindications, hypertension,
potentially Alzheimer's disease,is where Alnylam is headed and
I'm curious, Tolga, how youmanage that evolution and scale
from more rare diseaseindications to these very large
(43:47):
indications across thecommercial organization.
How do you scale that up?
Tolga Tangular (43:53):
Listen.
First of all, it's veryhumbling because to think that
you can actually come up with apotential solution of
essentially a public healthproblem that is inflicting pain
(44:14):
to millions of people isincredibly rewarding.
So I just want you to know likethis is an area where it gets
all of us excited every morning.
Now obviously it comes withreal challenges, because we
started in the beginning of ourconversation around how
complacent we are as humans, howdifficult it is to change and
(44:38):
how you need to start looking atit and start telling a very
different narrative.
Big part of commercializationactually becomes market
readiness and that requires alot of resources, a lot of
experiences and, frankly, asgreat as we are as Alnylam, we
also need to be humble aboutwhat we can do now and maybe
(45:01):
what we can actually need tobuild as a capability.
So I know we can do a lot interms of rare and even in
specialty conditions.
I think we have the rightcapabilities, right talent,
right infrastructure to be ableto commercialize these assets.
But actually dealing with amore broader public health
(45:22):
problem requires a largerorganization and a very
different mindset.
So this time around zilebesiranwith , as you know, we actually
chose a partner and I was a bigadvocate of doing that, even
though it's going to require usto share some of that value.
But I see it as the value thatwe can actually create even
(45:43):
bigger, more if we were to goalong.
So Roche actually has done agreat job in areas like multiple
sclerosis, even though that'sactually more of a special
disease.
Ben Comer (45:54):
Right CNS conditions yeah.
Tolga Tangular (45:56):
Exactly what we liked about them is with Ocrevus
, for instance, which is a verydifferent mechanism of action.
They completely looked at theecosystem very differently.
So I think that's what you needin a partner with similar
values and similar ambitions anda different mindset.
That will take us there.
So I think that was reallyimportant for us.
(46:18):
From a capability perspectiveyou talked about scale
Capability perspective you wantto work with a partner that you
can actually start buildingthose muscles.
So we are actually doing 50-50in the US where we are a
co-promoter, co-partner, andthen we're letting them
commercialize entire ex-US.
(46:39):
But the next opportunity, wewant to be able to actually
commercialize it by ourselves,Because by the time the next
large opportunity comes along, Ilike to think that we've
already had built thosecapabilities that I just shared
with you.
Ben Comer (46:55):
I've been told that the 50-50 commercial split was
pioneered by Regeneron.
Can you confirm or deny that?
Tolga Tangular (47:05):
I don't know.
I mean I don't know ifRegeneron did the deal before
Pfizer and BMS did on Eliquis.
I can tell you.
Ben Comer (47:12):
Oh on, eliquis right, yeah, yeah, that was a 50-50
split that was a 50-50.
Tolga Tangula (47:16):
Sanofi-Synthelabo and BMS.
Before Sanofi merged withAventis, they did a 50-50 for
their hypertension program, so Idon't know if it was really
pioneered.
It's a very smart strategy,especially if you're again early
innings of yourcommercialization.
Ben Comer (47:37):
Great I wanted to ask about.
You know, and this may not beimportant, it doesn't seem like
these laws are going anywhere,but I did notice that a few days
ago, Montana, you know, hadsome sort of preliminary vote on
a state law that would ban RNAvaccines entirely for human use.
(47:59):
Are you?
I mean there's been some noise,I think, in in Idaho, maybe in
Texas, none of these again, noneof these laws are close to
coming into effect.
But I'm curious, if it'ssomething that Alnylam is
following and you know to yourpoint about kind of setting the
table for new treatments,education being a, you know, a
(48:22):
key component of that, is thissomething that's on your radar
or not?
Do you think it's just sort oftalk?
Tolga Tangular (48:28):
Yeah, well, listen, first of all and first
and foremost, we're a very proudAmerican science organization
and our science is based onNobel Prize winning technology
and this company was founded in2002, and we've been the
pioneers of introducing anentirely new class of medicine.
(48:51):
As you know, there's a lot ofnoise out there and there's a
lot of sort of noise around.
You know genetics and you knowRNAi, mRNAi and you know, We're
(49:14):
neither a vaccine nor actuallyan mRNAi right.
We are actually essentiallyRNAi interference.
That is actually infrequent,but definitely, you know, not a
once and done kind of genetictreatment.
That fits very nicely into theexisting ecosystem of how
medicine is being treated.
(49:36):
And I think, once you explainthe science and showing the deep
, deep, deep, deep safetyinformation we have and
thousands of years of patientlives I mean we have now already
five products in the market andNovartis is obviously expanding
the aperture with ahypercholesterolemia product,
(49:58):
Leqvio even to many morethousands of patients we like
where we are in terms of ourtrack record, we like where we
are in terms of our science andtechnology and we believe we
need to continue to have thatdialogue if, if patients are
worried about or the, you know,lawmakers are worried about our
products.
(50:18):
We want to be out there and beable to engage the dialogue and
and continue to communicate.
So, look, look, because we'restanding on very firm foundation
of our science.
We have, I think, 13 or 14published studies on New England
Journal of Medicine andcountless other peer-reviewed
(50:40):
journals.
We stand very firmly on thosefoundations.
Now it's going to be a questionof are there going to be people
that are misunderstanding thescience and we need to explain
it?
I think that's part of the job,ben, and we're up for it
because we believe in what we'rehere to do and what we're here
to provide.
Ben Comer (51:01):
In our last couple of minutes here.
Tolga, why don't you share yourtop priorities for 2025?
Tolga Tangular (51:09):
Yeah, but look, I mean what's obviously very
close to everyone I think thewhole industry is an upcoming
launch on our ambutra with thecardiomyopathy indication, as
you may know.
Amvuttra with thecardiomyopathy indication as you
(51:29):
may know, we have a late MarchPDUFA date in the US and then
subsequently we look forward tolaunching the same indication in
Germany and Japan and the restof the world after the second
half of the year.
Now, that's an important launch.
Second half of the year Now,that's an important launch, not
just for the obvious reasons,but what will enable us, frankly
, is to continue to bring on atthe forefront of biotech
(51:57):
innovation.
As you pointed out, ourpipeline is a dream for many.
As you pointed out, on CNS, wehave assets in hypertension as
well as in hematologic disorders.
What this launch is going toenable us to do is to actually
(52:19):
create the cash flow that willenable us to actually fund these
, fund these importantinnovation that we're about to
set out to do so.
Probably, I would say 60, 70% ofmy time is really focusing on
the Amutra launch and, frankly,this is a focus area for us for
(52:40):
the last four years.
So that is, I just cannot waitto get out there and communicate
the benefits of this incrediblemedicine but at the same time
continue to actually focus ourorganization to make the right
bets on the pipeline and get themarket also ready for those.
(53:03):
Those are my sort of top ofmind.
In the meantime, we talkedabout scaling.
Look, the way I see it is.
We're building skyscrapers notjust one skyscraper, that's TTR.
Another skyscraper is the rare,but the many things can come in
neurological disorders and soforth.
What I want to make sure isthat the foundation that we're
(53:24):
building in the commercialorganization can apply to each
of those skyscrapers.
So that's certain foundationalcapabilities like AI, like how
do we actually continue togenerate data?
How do we actually build thoseaccess capabilities like
value-based agreements as aconsistent capability?
As a consistent capability, howdo we actually do omni-channel
(53:47):
marketing, so that you know theorganization.
We can focus on realvalue-based activities and
communication on one-on-one,peer-to-peer where it needs to
be and surround sound it withomni-channel capabilities.
These things are no longer pipedreams.
Right, these are actuallythings that we deal with and I
see great practices in ourorganization across the
(54:11):
categories.
But I want to actuallyconsolidate that because
essentially, we're building agenerational biotech.
If you want to build agenerational biotech, you need
to have the right foundations.
Some of my priorities also hasa lot to do with that, but first
and foremost, obviously,winning in TTR is going to be a
key priority and a key test forthe organization.
Ben Comer (54:36):
That is Tolga Tangular, executive Vice
President and Chief CommercialOfficer at Alnylam I'm Ben Comer
and you've just listened to theBusiness of Biotech.
Find us and subscribe anywhereyou listen to podcasts and be
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(00:44):
Welcome back to the Business ofBiotech.
I'm your host, Ben Comer, chiefeditor at Life Science Leader,
and I'm pleased to speak todaywith Tolga Tanguler, Executive
Vice President and ChiefCommercial Officer at Alnylam
Pharmaceuticals, an innovator inthe RNA interference or RNAi,
therapeutic space.
Tolga is a commercial leaderwith deep industry experience
(01:08):
who has helped commercializesome blockbuster brands you may
have heard of, such as Viagraand Eliquis.
He also led Pfizer's raredisease group for North America
before joining AlexionPharmaceuticals as senior vice
president and head of Alexion'sU.
S.
organization.
Tolga joined Alnylam in 2020and has been a key player in
(01:32):
expanding the company'sfootprint globally to more than
60 markets and dramaticallyincreasing patient access to
Alnylam's therapies.
Thanks for being here today,Tolga.
Tolga Tangular (01:39):
Great to see you , Ben.
Thank you for having me.
Ben Comer (01:42):
Absolutely.
I wanted to start with how yougot into this line of work.
What attracted you initially topharmaceutical drug marketing
and commercialization?
Tolga Tangular (01:53):
Yeah, thank you Ben, and I wish I could tell you
that there was this great,great grand plan for me to join
the industry, but it came a bitof, I think, a happenstance, and
I feel very fortunate to bepart of the industry, looking
back after 25, 30 years.
Essentially, my family is a goodmix of a business executive and
(02:17):
my mom is a psychologist whohas been in the medical industry
, so medicine was not a newterritory for me.
While I was at business school,I had a number of offers, one
of which was actually an offerfrom Merck that was part of the
(02:38):
leadership development program,which really fit very nicely
with something that my fatheralways used to say, which is, if
you want to do something and ifyou want to lead something,
learn from the bottom andunderstand how actually the
sausage is being made.
So Merck Leadership Program wasactually a great opportunity
and that's why I actually pickedit.
And, of course, again, science,medicine, technology were in
(03:01):
areas that were too unfamiliarfor me.
So that was actually a greatstart.
And again, I've been veryfortunate being associated with
great companies like Pfizer,Merck in the beginning, Pfizer
throughout my formative career,and then, as you mentioned, I
had the opportunity to join thebiotech world, first with
(03:22):
Alexion and now last four orfive years with Alnylam, which
has been just a phenomenal ride.
Ben Comer (03:29):
Yeah, you went from gigantic drugs to rare drugs and
now you know Alnylam might beheading back.
The pendulum may be swingingback towards some larger patient
audiences.
I have to ask you about workingon Viagra.
What was that experience like?
Was that the first big brandthat you worked on?
Tolga Tangular (03:49):
It was.
And, frankly, what's reallyinteresting, I was given an
opportunity to work either withCelebrex or Viagra and I made
the decision early on that Iwould actually work on Viagra.
A what an iconic brand, and whowouldn't like to kind of learn
and understand how an iconicbrand works?
And the second piece of it was,unlike most of our medicines in
(04:14):
those erectile dysfunctioncategory, doctors tend to
abdicate the sort of writingthese products to their patients
.
So I felt like I'm going towork with science and I'm going
to work with these very uniquetherapies throughout my career.
But Viagra will probably comeonce in a lifetime where you
actually get to understand howpatients think through, and it's
(04:38):
obviously in those daysespecially.
It was a stigmatic category andworking in a stigmatic category
and working in a stigmaticdisease area and working with
the patients was very intriguingto me and, frankly, I never
looked back after the experience.
It really allowed me tounderstand how patients think
and how to actually helppatients with a condition that
(05:02):
is so stigmatic.
Ben Comer (05:04):
Yeah, absolutely.
In the late 90s I was workingin a mom and pop pharmacy is
actually a compounding pharmacyand I remember the Viagra sales
team coming in, which maybe youcan answer this question for me
before I tell this short story,I promise.
Tolga Tangular (05:22):
I want to talk more on biotech, but yes, let's
talk about Viagra.
Ben Comer (05:26):
Yeah, just for a second.
Tolga Tangular (05:27):
Bear with me here.
Ben Comer (05:28):
I was always curious about why the sales detail team
came into a pharmacy, given thatthe pharmacists weren't writing
prescriptions.
Can you clear that up for me?
Tolga Tangular (05:38):
Yes, yes, actually.
In fact, when I was a year,when I started my rotation
program at Merck, I spent in thefield a year and we were asked
to go into these pharmacies.
It was mainly because youwanted to understand how the
pharmacists reacting to thepatient needs and also
(05:58):
understand if they see anydemand, so we would actually
just talk.
It was always a bit of anoptional call in those days.
I don't think we do thatanymore as an industry and you
have, you know, ability tocapture a lot of data and
insights through third partywithout going to these
pharmacies, but it was actuallya bit of an industry standard in
the 90s.
(06:18):
You're spot on.
Ben Comer (06:19):
Yeah, well, what I remember from the sales detail
folks that came through was aViagra calculator that you may
remember this.
It was flat and you pushed abutton on it and the top kind of
rotated around and thenultimately stood the calculator
up a little bit, which we were,you know, as a high school male,
I was very, very tickled by.
Tolga Tangular (06:40):
But anyway, well , listen, those are some of the
practices that I'm so glad thatthe industry moved away from.
Ben Comer (06:46):
Well, I was going to use that as a segue to ask you
you know how launching andcommercializing new therapies
has changed since you worked onon Viagra in the early aughts.
Tolga Tangular (06:57):
Yeah, I mean listen, like everything, the
industry had some growing up todo and I think we did.
And obviously the diseases thatI'm so keen on commercializing,
(07:19):
which is simply a word meaninghow do we get this product value
back to our companies thatcontinue to innovate for
transformative diseases thatpatients that need the most?
So that's been my passion andthat's how we've evolved, and
what I really like about thespace that we're in has a lot to
(07:41):
do with the words that I justused, which is high medical
needs and transformativetherapies, and society right now
, in the right way, startvaluing and rewarding those
actually products that trulymake a difference, so that you
know you don't get to work on,spend a lot of human and capital
(08:03):
to areas where you're justdeveloping a me-too product that
is no longer acceptable andthat's not where you generate
value.
And let me tell you alsoanother personal story about why
I'm so keen on actually workingon those products.
It has a lot to do with my sonand his journey.
(08:24):
Products has a lot to do withmy son and his journey In about
the middle of my career this isjust before I start leading the
rare disease unit in NorthAmerica for Pfizer.
My son was diagnosed withleukemia childhood leukemia.
He was 11 years of age and eventhough, you know, I was in the
(08:44):
middle of my career in thepharmaceutical biotech industry
and I always thought I was verypatient focused and I always
cared about the impact that ourmedicines, or potential
medicines, will make on people.
But, boy, when that hits you inyour family in a very personal
way, you start looking at thingsvery differently.
(09:07):
And, frankly, that was one ofthe reasons why I was attracted
to Rare, because you knew thatthe impact that individual
impact you can make is reallyprofound on a single life.
And now, obviously, with thetherapy areas that we're working
on at Alnylam for the future,is what really excites me is you
(09:29):
can actually make thoseprofound impact in a much
broader population.
And what's so great aboutAlnylam is and I guess we'll get
into this is the technologyplatform that we have that
enables us to do, whether it's asingle genetic mutation
condition or a protein that mayactually impact a significant
(09:50):
illness like hypertension orhypercholesterolemia.
Ben Comer (09:54):
Yeah well, thanks for sharing that story.
Did your son survive?
Tolga Tangular (09:57):
He did I should have said that, yes, he's an
annoying 20-year-old collegestudent.
He's doing great, and we allrecognize that none of those
things are for granted.
Ben Comer (10:09):
Yeah, yeah.
Well, I'm happy to hear that Iwanted yeah.
Tolga Tangular (10:14):
And, by the way, I mean, let me add this he
wouldn't have survived if itwasn't for our industry and
science, because only 50 yearsago this was a death sentence.
Now the prognosis rates are asgood as 90%.
So that's the progress that weneed to continue to make,
because there are a lot of kidsout there, there are a lot of
adults out there whose illnessesare not transformed yet, but we
(10:40):
were very lucky that we gotinto that bucket of diseases
that science and medicine havefigured out a way to solve it.
Ben Comer (10:50):
What would you say is different about launching and
commercializing an RNAi drugversus other more established
drug modalities?
And I'm thinking you know wehad a short call just to prepare
for this podcast Tolga, and youknow one of the things that
(11:26):
that came up was this kind ofyou know, I don't know if drug,
but also how you bring such anew modality to physicians and
overcome, you know, some ofthose kinds of resistance to
change that they might present.
Tolga Tangular (11:41):
Right, yeah.
So I mean, listen, I find it,to be honest, is an opportunity.
I think we talked about Eliquisand, how you know, at the time
we had head-to-head data, bothon the primary endpoints, like
you know stroke prevention andrisk reduction, and safety
(12:03):
versus Coumadin, which is a50-year-old product that's been
out there for blood thinning,and essentially, even though you
had a head-to-head trial thatshowed superiority versus
Coumadin, in both on primaryendpoints as well as on safety,
(12:23):
doctors were not willing to makethe change.
They all felt, like you know,they were able to control the
patient's bleeding, which wasnot an easy dosing, and then you
had to get liver enzyme testsand everything, and that took us
a while.
So there is, I guess, aninherent condition in all of us,
and also with doctors, to be alittle skeptical about new
(12:45):
treatment options.
What's so great about, I think,what Alnylam provides and
allows us to rethink is the factthat you can literally do a
subcutaneous injection everythree months to, you know,
lessen the hypercholesterolemia.
(13:05):
One of our products is rightnow being marketed by Novartis.
It's a product named Leqvio.
So that is.
You know, I see that thenumbers are picking up.
That is exactly the examplewhere how doctors tend to resist
.
Now I find that also gives us anopportunity to completely
(13:27):
rethink how medicine ispracticed.
We're currently working on aproduct called Zilebesiran that
is subcutaneous in the injectionevery six months that lowers
potentially lowers systolicblood pressure.
Now we have several highlyeffective medicines that are out
(13:48):
there that lowers bloodpressure and they are
inexpensive.
Yet, for any account, there isabout 20 million Americans that
suffer uncontrolled bloodpressure that results in stroke
and other significantconsequences of blood pressure.
So why is that?
Well, one of the answers isactually probably patients are
(14:11):
not taking their medicines everyday.
Once a day pill or twice a daypill, as sound, as simple as it
is.
Now I'm that age where I'mtaking some of those medicines.
I can tell you I miss them andI know what the consequences are
.
So bringing a medicine that ishighly effective and safe and
(14:31):
with a simple subcutaneousinjection that you visit your
doctor or a nurse comes in yourhome and injects you, opens up a
whole set of opportunities.
That really excites me, becausecommercializing a new
technology in that respect isreally, really, I think,
advantageous.
But it's going to require us toalso challenge ourselves to see
(14:54):
how we actually bring some ofthose opportunities in mind.
Now, the other plus I thinkthat we have that maybe amazing
gene therapies, therapy optionsare actually struggling is we're
not one and done.
You know, we're not actuallyrequired to change how we get
(15:17):
reimbursed.
Actually, we fit nicely intothe reimbursement structure that
is currently set for medicinesthat are taken regularly.
We don't need to actually priceour disease as one and done,
which actually gives us someadvantages to actually work
within the existingreimbursement system.
And those are, I would say,actually it's not going to
(15:39):
require us to change.
But at the same time, thesetreatment regimens that are
actually infrequent and simple,with a subcutaneous injection,
may give us sort of anopportunity to force the health
care system to rethink howmedicine is practiced.
Ben Comer (16:00):
You know.
That brings to mind for me, youknow, a key commercial issue
that I wonder if you know I'msure some of our listeners for
the business of biotech willknow about this Others may not
though which is the gross to netissue.
And I noticed in fourthquarter and 2024 earnings report
(16:22):
that there were some positivegross to net adjustments made in
the US during the fourthquarter, and I wonder, Tolga,
would you mind just giving abrief, very high level
explanation of what gross to netis?
Tolga Tangular (16:37):
Yeah, essentially it's the the your
products revenue minus, you know, minus essentially your
royalties and rebates and costof goods.
So that's how you know grossnet is adjusted.
And look, I mean, I think it'sa it's a question of for a
(17:00):
company that is destined to tochange how medicine is practiced
.
We need to continue to forceourselves and our organization,
how our cost of goods isactually continuing to be
brought down.
And this is an area whereobviously we're not a biologic,
(17:23):
we're also not a small molecule.
Our manufacturing is complexand it's not cheap, but we
certainly believe, unlike a genetherapy cost or even a biologic
cost, we have an opportunity toactually to continue to further
reduce cost.
Our CEO to continue to furtherreduce costs.
(17:43):
Our CEO, Yvonne Greenstreet,has this vision of democratizing
RNAi, meaning try tomanufacture it as inexpensively
as possible so we can actuallymake it available not just in
the US but in other marketswhere cost is even a more bigger
sensitivity.
We're trying to obviously makethat happen.
(18:04):
Now, specific to the Q4 resultsthere's always going to be ins
and outs how those rebates areactualized.
There's some also timing ofsome of those rebates, how
they're actually beingrecognized.
So I wouldn't necessarily paytoo much attention to quarterly
(18:25):
changes.
What's really helpful is tolook at the annual metrics, and
those obviously metrics willalso continue to evolve.
Ben Comer (18:34):
Right and just for the benefit of our listeners
gross to net.
Gross obviously meaning whatthe product is sold for.
Net is what you're actuallymaking on the product and a lot
of times the criticism of thisso-called gross to net bubble
has to do with rebates.
Now, Tolga, you're reducing thecost of goods, so that's an
excellent way to improve grossto net and, similarly, fixing
(18:58):
the compliance issue, which I'vebeen a journalist covering
biopharmaceuticals for close to15 years and for a while there
it seemed like once a year I'dwrite the adherence and
compliance article and somebodyhad a new idea about how to
improve it.
It never improved.
You know we still.
It's an ongoing challenge, butyou know, when you have a shot
(19:19):
that you can give over a courseof months, you're, you're taking
yourself out of that compliancequandary.
Similarly, with lowering thecost of goods, you're setting
yourself up for success in grossto net, at least in terms of
things you can manage.
Tolga Tangular (19:38):
No, you're spot on, Ben, because I mean, look,
just like you.
Over the years when I worked onespecially on tablets, both the
industry as well as likepharmacists I've seen
pharmacists actually have thesedevices that every time you open
the pill tab it would actuallysend a message whether you're
(19:59):
compliant or not.
So the whole industry has beenworking around this issue,
around tablets, and we haven'tfound anything, because I think
inherently, taking a pill everyday or twice a day is not a
normal human condition.
Now again, there are people whoare incredibly adherent.
But even in oncology we seeadherence rates as low as 70
(20:20):
percent I mean this is cancer.
Rates as low as 70% I mean thisis cancer In more you know,
sort of metabolic diseases wesee rates at 60%, 70%.
So if we can actually solvethis by simply how patients take
their medicine every threemonths, every six months in
physician office or a nursepractitioner visiting your home,
(20:42):
I think we will go a long way.
And I don't think we actuallywe can't overestimate the human
health impact that's going to bemade on the patients.
And if you look at our currentproducts, our adherence rates
are 90, 95% every category thatwe work on.
So there's something obviouslyto be said about how our
(21:06):
medicines are administered.
Ben Comer (21:08):
Yeah, I mean.
The other thing about a dailytablet and compliance to me is,
you know, particularly maybe indisease areas like cholesterol
or even diabetes.
I think one of the majorchallenges is that if you miss a
dose, nothing really happens.
There's no consequence rightaway from missing a dose.
(21:29):
It's taking it over a period oftime and missing doses, and so
when you're not automaticallyfeeling better because you took
your cholesterol medicine on agiven day, it makes it difficult
to really incentivize.
Tolga Tangular (21:45):
You're spot on, and as an industry, I think we
face two major hurdles.
One is the physiciancomplacency, because if you can
do this yourself, or thosecolleagues that are watching
this, should do that.
If you ask any doctor in anytherapy area whether their
patients are actually adherentor compliant, they'll say yes.
Ben Comer (22:10):
Of course right.
Tolga Tangular (22:12):
So there is that , I think, issue.
And then, to your point,patients, yeah, if I miss my
statin or hypertension, butagain I'm giving you some
numbers, even in cancer, wherepatients actually don't take
their medicine, or maybe theyneed a caregiver that needs to
do that and they don't have thesocioeconomic, you know, setup
(22:32):
to be able to do that.
And we see it mostly onpediatric patients.
And if the caregiver is, youknow, less educated or a single
parent that's working, thosecompliance rates tend to go down
.
So this is an area where Ithink we need to continue to
work as an industry, and onesolution is obviously come up
with better medicines that aretaken less frequently.
Ben Comer (22:57):
I mentioned in the intro Tolga about Alnylam's
global expansion.
Almost half of the company'srevenues now are coming from
ex-US markets.
What can you say about thestrategy that Alnylam followed
to accomplish this and what aresome of the biggest challenges
(23:17):
in building a large and growingglobal footprint?
Tolga Tangular (23:22):
Yeah, I mean, first and foremost, I don't
think I can take the full creditof the online expansion
strategy, because those actuallywho founded the company always
had this really bold vision and,frankly, since I've arrived in
four or five years ago, whatI've been able to do is to
(23:42):
actually embolden that strategyeven further.
Now to your point.
We do generate about 40% 45% ofour revenue.
We continue to grow in terms ofvolume about the same rate that
you would see in the US and,frankly, it's mainly driven by
(24:02):
how I believe we're approachingour expansion.
And for a small biotech, Ithink we're punching way above
our weight and I don't think weever look back about having that
international presence.
But we do it very thoughtfullyand very carefully because
actually it can put a strain onyour resources.
Having that geographicfootprint, put a strain on your
(24:27):
resources having that geographicfootprint, but the potential
benefit of investing a littlebit on your ex-US markets
actually happens, that youactually balance your revenue
flow.
So that's actually a big plus.
You start finding opportunitieswhere there might be some
endemic regions that are less inthe US.
We certainly see that in ourultra-rare disease area and as
(24:49):
you grow you don't need to leavea lot of value on the table for
a third party or distributorthat actually ends up actually
really commercializing yourproduct, where you get to keep
that value again to transfer itinto your research and
development.
You get to keep that valueagain to transfer it into your
research and development.
(25:11):
So, with that outlook, what wedid is we started looking at the
globe not just geographically,but actually we looked at it
from an archetype market,archetype perspective.
And what do I mean by that is,if I look at geographies like
Europe, there are actually many,many archetypes within that
European geographies like Europe.
There are actually many, manyarchetypes within that European
geographies.
You have developed markets likeUK, Germany, Spain, Italy,
(25:32):
where there's value that's beinggenerated by good reimbursement
system, good healthcare system,where you have access to new,
innovative therapies.
But you also have markets whereI don't know Turkey, Greece.
You know Eastern Europeanmarkets where access to medicine
is less likely and where youdon't want to probably spend a
(25:54):
lot of time and energy incommercializing and have someone
else do it, because the juiceis not simply enough, the
squeeze.
Now, when I look at SoutheastAsia, I see more similar markets
like the ones that I justdescribed with you, like the
distributor markets like Vietnamand Korea and Singapore, where
(26:16):
you actually, again, you maywant to go to a distributor and
not have your own directfootprint.
But then you have Japan, thatactually very similar markets,
like Germany and UK and Spain.
So what we did is we said let'slook at the market archetypes,
let's combine those markets thatare similar under one roof and
(26:39):
that's our international marketthat actually spans through
Canada all the way to Japan,including all major European
markets.
And then, when it comes tothose distributor markets and we
call them affectionately ourpartner in emerging markets
let's consolidate with few.
So, instead of having work withlike 10, 12 different
(27:01):
distributors, let's keep them afew, two or three of them, so we
can actually expand throughthem.
That actually helps us toactually minimize disruption,
deepens our relationships and,by the way, it allows us to make
them more compliant.
We actually have these partneremerging markets that we work
(27:23):
with a few of them and we expandthrough them, and then we
obviously treat our US as oursingle most important market.
And then the rest of the worldwe call them partner and
emerging markets.
Now, the other category we haveis our global rare business
units.
So, unlike our TTR franchise,where we really focus on
(27:46):
market-by-market opportunity,our ultra-rare market, we
actually consolidate our expensebasis in a very small footprint
and our global rare franchiseoperates as an end-to-end
business unit and that actuallygives us a lot of efficiencies
and also allows us to focus on.
Not all markets in ultra-rareare equal.
(28:08):
So our global rarity maybefocus more on Middle East
markets where we see endemic onhyperoxaluria, but then we don't
go and maybe work too deeply onFrance for instance, because
the opportunity may not be asbig as some of the markets in
the Middle East.
Ben Comer (28:28):
Yeah, that makes a lot of sense.
I'm curious about what factorsyou consider when you're
deciding whether or not topartner with a distributor or go
as Alnylam.
How do you make that call?
Tolga Tangular (28:43):
That's a great question.
First of all, it's a verynuanced call and there's no one
single playbook.
But what we look at, of coursethe longevity and the growth
trajectory of the particularcategory For any particular time
point.
We say, look, do we have theresources right now Because
we're just about to becomeprofitable this year?
(29:05):
Right, that's what we declared.
So we still need to look at oursales and administrative costs.
We look at, then, thecomplexity of the market Are we
going to be able to actuallybuild the regulatory muscles
that we need to have?
And again, if the longevity,the sustainability of that
(29:26):
growth, is worthwhile, then wego after it.
I'll give you one example.
Actually, it's interestinglyoriginally Australia was a
market where we said it's partof this sort of archetype where
it needs to be under ourinternational market, because
you have socialized medicine,you have access to patients and
(29:48):
it's reimbursed.
So we said let's go and workand have our footprint.
Then, actually, our partner inthe emerging markets, lider,
gave us a challenge.
He said I can actually makethis product available faster
and I can actually do it with alower cost base.
So both teams got together andactually we ran a business
(30:10):
simulation and we ended upactually saying you know what?
For now, let's actually go anddistribute this market with a
trusted partner that we alreadyknew, and you know what?
They beat those timelines andwe actually made one of our
products available already inAustralia much faster than we
would ever imagine if we were togo there faster.
So, as I'm explaining, there isno real one single playbook.
(30:34):
There are principles that welook into and then we make the
decision accordingly.
Ben Comer (30:39):
That's really interesting.
Who is the partner in Australia?
Tolga Tangular (30:44):
It's a company called Medison which we actually
partner with multiple markets.
Ben Comer (30:52):
Great.
What role, Tolga, does pricingplay in mapping out market
entrance strategy globally?
I mean, do you think aboutcountry sequencing and price?
How do you think about that?
Tolga Tangular (31:05):
Yeah, first of all, I mean, of course, to your
point, it's a bit of an industrystandard to make sure that we
actually really understand andappreciate cross-border impact
of how it's priced and also ifwe were to sort of be dealing
(31:25):
with reference price impact andso forth.
But I think what's reallyexciting about Alnylam and again
this is an area where I like tothink that we've been punching
above our weight is, before weeven commercialized our first
product, we came up with apatient access philosophy and
that patient access philosophyhas been actually sort of the
guiding light for us.
(31:46):
We're never going to increaseour price above inflation and if
you look at our pricing overthe years now we have been
commercializing products for thelast five, six years we made
very few price increases, ifthat ever, and that's always
been under inflation.
So that's been number one.
Number two is we play to ourstrength of our science and our
(32:12):
platform technology.
We only promote and make ourproducts available that are
transformative as medicines.
So we're, essence we alwayskeen on what's the value to the
society.
How am I going to actuallyinterpret that for the payer?
Then, the last but not least,what's the patient affordability
(32:34):
is going to be?
It's one thing to put your listprice and to your point.
In the US we also have thisrebates that we need to work
with.
It's an imperfect system.
We don't like it, but that'sthe system that we're currently
working on.
And then it becomes thisquestion about what's the impact
(32:55):
on the patient.
Is the patient going toactually have to pay the copay?
Are there programs that we canmake that happen?
Are there things that we canwork with the payers?
We have been pioneeringvalue-based agreements.
Now those value-based agreementsare essentially about really
putting your money where yourmouth is.
(33:16):
So if I'm negotiating with apayer and saying, look, we
believe the patients will stayon therapy and they're not going
to have to deal with theconsequences of the disease,
albeit maybe organ transplant orpatient, if they stay on
therapy, they're not going to behospitalized.
Depending on the label,depending on the agreements, I
can't disclose a lot of those,but what I can tell you is we're
(33:40):
now covering about 60 percentof those patients that are
covered under commercial orMedicare advantage through these
value-based agreements roughlyabout 55% of those.
So those really actually helpus.
So it's not just the cost orthe price, it's how do you
actually build the ecosystemaround that that enables us to
(34:01):
actually go in and provide thevalue narrative around the
payers.
Ben Comer (34:08):
Yeah, I want to get into this value-based contracts
topic a little bit.
It's something I probably firstwrote about, this idea of
value-based contracts, I don'tknow 10 or 12 years ago and it's
kind of gone up and down interms of interest and popularity
and value-based contracts.
I think, like so many things,there was great excitement at
(34:31):
the beginning and then some kindof reality seeped in where
people found out it's.
You know it's not so easyalways to manage these kinds of
contracts, assess them.
You know across sort of agreedupon points and you know the the
lifestyle, life cycle of themedicine or even in the
patient's health.
Could you, would it be possible, tolga, to give us an example
(34:53):
or two of a value-based contractthat Alnylam is involved with,
sort of from soup to nuts.
Explain you know what productsinvolved, how it works.
Soup to nuts.
Explain you know what productsinvolved, how it works, how you
assess it, how it's managed.
Tolga Tangular (35:06):
Right.
So just up front, you know I'llbe able to give you some flavor
, but not all the all thespecifics, but I'm sure it's
going to be helpful for youraudience.
But look, I mean, let's, let'salso take the first point you
just made.
Um, you have to stick with it,right?
So one of the great, I think,skills, or the values that we
(35:31):
have as Alnylam, is being veryresilient.
So when RNAi was in favor, wewere there and RNAi wasn't in
favor, a lot of these big pharmacompanies pulled out we were
still there.
And value-based agreement is abit like that too.
If you believe in the theoryand if you believe in the
practice, working with somepartners, in the long term it
(35:57):
actually gives you credibility.
You also learn from each otherand you start building this as a
real capability.
So you can't just treat this asa flavor of the month, and
because of that, I think I cankind of safely talk to you about
some of the programs we have.
So you want me to be a littlespecific.
(36:17):
So let me give you a fewexamples, one of which is in
ultra-rare, ultra-rare.
So in ultra-rare, what youusually see is, especially in
the United States, per treatmentcost tends to be higher than
(36:40):
your other treatments andtherefore payers avoid sort of
end up with these patients.
But if you're around there andif you're covering many lives,
you're going to end up with somepatients.
Unfortunately, frankly, not allthese rare conditions, a very
small percentage of these rareconditions, are actually now
diagnosed and treated.
But when you get them, what youworry is how am I going to
(37:03):
manage this cost inflation andis this going to be impacting my
level of predictability?
And, as you know, insurers careabout the cost but they care
more about predictability.
So one of the things we didwith the value-based agreements
is we said look, according toeverything that we see and the
(37:24):
prevalence numbers that we seein ultra-rare, we're going to
cap some of the costs if anumber goes way above what that
prevalence ratio should show,based on all the population and
epidemiology data that we have.
Ben Comer (37:43):
So that provides yeah , you're giving them some
predictability, exactly.
Tolga Tangular (37:47):
So that's one angle.
Another angle that we do withour TTR franchise is we look at
clinical outcomes.
We say, look, according to this, here's how the patient should
behave, and if you don't, thenwe're actually willing to
provide you a certain rebate ora discount or refund based on
(38:09):
the given, the value-basedagreement.
So by doing this again, we Aprovide.
Frankly, it also shows ourconfidence about look, our
medicines are based on geneticinformation, based on the
biology, human biology, so itgives us a lot of predictability
and confidence that ourproduct's going to work.
And now we're just about tofinalize our CV outcomes study
(38:36):
on our cardiomyopathy, thelabeling I should say we just
published the Heliospeed.
So we know these products work,we know that actually it
provides a real benefit to thepatient.
So why not actually tell thepayer that we stand behind those
data points?
(38:56):
And that again gives us anenough.
Is every payer willing to do it?
No, because, to your point, noteverybody is equipped to do the
administration of how to followup these patients.
They say, ah, by the time ittakes me to actually follow up
the patient and administer this,it's going to get more costly.
But in some cases we simplifythe administration and in most
(39:22):
cases we do, so that actuallyworks really well.
And then some payers believe inthis and they like what they
see and they stick with us.
Some payers don't prefer it,and that's OK.
Ben Comer (39:32):
So you're working directly with the insurers to
help set up this, this wholeprogram of how they can manage
results.
Do you find?
I mean, does it work betterwith insurers?
Tolga Tangular (39:42):
Some governments , by the way, sort of interrupt
you, but in some cases we dowork ex-US with some governments
.
Ben Comer (39:48):
With governments as well, right?
Do you look for health insurersor governments who have some
experience in these kinds ofdeals, or are you also building
some of you know forging thesefor the first time with some
health insurers?
Tolga Tangular (40:02):
It's a little bit both.
Frankly, those who have startedthe journey five, six years ago
with us, they like what theysee, so they stick with us and
in some cases we publish andshow them hey look, this is what
your competitor is doing.
Wouldn't you like to be part ofthis?
And especially those plans thatlook at the totality of the
(40:24):
patients, that are wellintegrated networks.
They really like this.
So they not only have theinsurance system, but they also
they cover the patient at thepayer side and also provider
side, so they actually fund theyou know, the hospitals, those
systems.
They really like that those,those systems.
Ben Comer (40:50):
They really like that , right?
Yeah, um, I wanted to um moveon to alnylam, you know, kind of
crossing back over into intolarger therapeutic indications.
But before we leave raredisease, I wanted to ask you
about diagnosis, which is acritical aspect of rare disease.
Getting the right diagnosiscritical.
I'm wondering, uh, what alnylamdoes, what kind of work Alnylam
does in terms of helpingpatients get diagnosed?
(41:11):
What can you tell me about that?
Tolga Tangular (41:13):
So that's your spot on.
The ultimate test is once youmake the product available.
We immediately see, first ofall, a pool of patients that
were already diagnosed and theyare desperately looking for an
option and we go and make surethat you treat that.
But then you need to actuallycontinue the pool of patients,
(41:35):
the flow of patients that arecoming in down the pike, and get
them treated early.
So making the product availableis actually a big leap forward
in itself because it increasesawareness.
The second point is we alsowork with you know diagnostic
companies.
If it's a hereditary disorder,we work with you know genetic
(41:59):
counselors, actually geneticdiagnostic companies that
provide genetic testing andassays available for the
providers.
So it's essentially reallybecomes a question of where is
the problem?
Is it really about sort ofgenetic testing?
(42:21):
Genetic testing Is it reallyabout awareness or is it
actually really?
improving the non-invasive waysto diagnose the patient.
In one instance, for instance,in TTR, we've been fortunate
enough to have scintigraphy.
Essentially, it's an imagingtool that is widely available in
(42:48):
the US, but you can actuallymake it multi-purpose and by
taking a different dye you'reessentially having the
accumulation of amyloidosis inyour body light up.
It wasn't invented for that.
Now one of the institutionsthat we work very closely
figured out that it can be usedfor that purpose.
(43:09):
So how do you actually makethat available?
How do you actually disseminatethat information?
So it's really a question ofunderstanding the value chain
where they actually you getstuck in patient diagnosis and
start identifying that andworking with the ecosystem.
Ben Comer (43:25):
Excellent, that's great.
Getting back to largerindications, hypertension,
potentially Alzheimer's disease,is where Alnylam is headed and
I'm curious, Tolga, how youmanage that evolution and scale
from more rare diseaseindications to these very large
(43:47):
indications across thecommercial organization.
How do you scale that up?
Tolga Tangular (43:53):
Listen.
First of all, it's veryhumbling because to think that
you can actually come up with apotential solution of
essentially a public healthproblem that is inflicting pain
(44:14):
to millions of people isincredibly rewarding.
So I just want you to know likethis is an area where it gets
all of us excited every morning.
Now obviously it comes withreal challenges, because we
started in the beginning of ourconversation around how
complacent we are as humans, howdifficult it is to change and
(44:38):
how you need to start looking atit and start telling a very
different narrative.
Big part of commercializationactually becomes market
readiness and that requires alot of resources, a lot of
experiences and, frankly, asgreat as we are as Alnylam, we
also need to be humble aboutwhat we can do now and maybe
(45:01):
what we can actually need tobuild as a capability.
So I know we can do a lot interms of rare and even in
specialty conditions.
I think we have the rightcapabilities, right talent,
right infrastructure to be ableto commercialize these assets.
But actually dealing with amore broader public health
(45:22):
problem requires a largerorganization and a very
different mindset.
So this time around zilebesiranwith , as you know, we actually
chose a partner and I was a bigadvocate of doing that, even
though it's going to require usto share some of that value.
But I see it as the value thatwe can actually create even
(45:43):
bigger, more if we were to goalong.
So Roche actually has done agreat job in areas like multiple
sclerosis, even though that'sactually more of a special
disease.
Ben Comer (45:54):
Right CNS conditions yeah.
Tolga Tangular (45:56):
Exactly what we liked about them is with Ocrevus
, for instance, which is a verydifferent mechanism of action.
They completely looked at theecosystem very differently.
So I think that's what you needin a partner with similar
values and similar ambitions anda different mindset.
That will take us there.
So I think that was reallyimportant for us.
(46:18):
From a capability perspectiveyou talked about scale
Capability perspective you wantto work with a partner that you
can actually start buildingthose muscles.
So we are actually doing 50-50in the US where we are a
co-promoter, co-partner, andthen we're letting them
commercialize entire ex-US.
(46:39):
But the next opportunity, wewant to be able to actually
commercialize it by ourselves,Because by the time the next
large opportunity comes along, Ilike to think that we've
already had built thosecapabilities that I just shared
with you.
Ben Comer (46:55):
I've been told that the 50-50 commercial split was
pioneered by Regeneron.
Can you confirm or deny that?
Tolga Tangular (47:05):
I don't know.
I mean I don't know ifRegeneron did the deal before
Pfizer and BMS did on Eliquis.
I can tell you.
Ben Comer (47:12):
Oh on, eliquis right, yeah, yeah, that was a 50-50
split that was a 50-50.
Tolga Tangula (47:16):
Sanofi-Synthelabo and BMS.
Before Sanofi merged withAventis, they did a 50-50 for
their hypertension program, so Idon't know if it was really
pioneered.
It's a very smart strategy,especially if you're again early
innings of yourcommercialization.
Ben Comer (47:37):
Great I wanted to ask about.
You know, and this may not beimportant, it doesn't seem like
these laws are going anywhere,but I did notice that a few days
ago, Montana, you know, hadsome sort of preliminary vote on
a state law that would ban RNAvaccines entirely for human use.
(47:59):
Are you?
I mean there's been some noise,I think, in in Idaho, maybe in
Texas, none of these again, noneof these laws are close to
coming into effect.
But I'm curious, if it'ssomething that Alnylam is
following and you know to yourpoint about kind of setting the
table for new treatments,education being a, you know, a
(48:22):
key component of that, is thissomething that's on your radar
or not?
Do you think it's just sort oftalk?
Tolga Tangular (48:28):
Yeah, well, listen, first of all and first
and foremost, we're a very proudAmerican science organization
and our science is based onNobel Prize winning technology
and this company was founded in2002, and we've been the
pioneers of introducing anentirely new class of medicine.
(48:51):
As you know, there's a lot ofnoise out there and there's a
lot of sort of noise around.
You know genetics and you knowRNAi, mRNAi and you know, We're
(49:14):
neither a vaccine nor actuallyan mRNAi right.
We are actually essentiallyRNAi interference.
That is actually infrequent,but definitely, you know, not a
once and done kind of genetictreatment.
That fits very nicely into theexisting ecosystem of how
medicine is being treated.
(49:36):
And I think, once you explainthe science and showing the deep
, deep, deep, deep safetyinformation we have and
thousands of years of patientlives I mean we have now already
five products in the market andNovartis is obviously expanding
the aperture with ahypercholesterolemia product,
(49:58):
Leqvio even to many morethousands of patients we like
where we are in terms of ourtrack record, we like where we
are in terms of our science andtechnology and we believe we
need to continue to have thatdialogue if, if patients are
worried about or the, you know,lawmakers are worried about our
products.
(50:18):
We want to be out there and beable to engage the dialogue and
and continue to communicate.
So, look, look, because we'restanding on very firm foundation
of our science.
We have, I think, 13 or 14published studies on New England
Journal of Medicine andcountless other peer-reviewed
(50:40):
journals.
We stand very firmly on thosefoundations.
Now it's going to be a questionof are there going to be people
that are misunderstanding thescience and we need to explain
it?
I think that's part of the job,ben, and we're up for it
because we believe in what we'rehere to do and what we're here
to provide.
Ben Comer (51:01):
In our last couple of minutes here.
Tolga, why don't you share yourtop priorities for 2025?
Tolga Tangular (51:09):
Yeah, but look, I mean what's obviously very
close to everyone I think thewhole industry is an upcoming
launch on our ambutra with thecardiomyopathy indication, as
you may know.
Amvuttra with thecardiomyopathy indication as you
(51:29):
may know, we have a late MarchPDUFA date in the US and then
subsequently we look forward tolaunching the same indication in
Germany and Japan and the restof the world after the second
half of the year.
Now, that's an important launch.
Second half of the year Now,that's an important launch, not
just for the obvious reasons,but what will enable us, frankly
, is to continue to bring on atthe forefront of biotech
(51:57):
innovation.
As you pointed out, ourpipeline is a dream for many.
As you pointed out, on CNS, wehave assets in hypertension as
well as in hematologic disorders.
What this launch is going toenable us to do is to actually
(52:19):
create the cash flow that willenable us to actually fund these
, fund these importantinnovation that we're about to
set out to do so.
Probably, I would say 60, 70% ofmy time is really focusing on
the Amutra launch and, frankly,this is a focus area for us for
(52:40):
the last four years.
So that is, I just cannot waitto get out there and communicate
the benefits of this incrediblemedicine but at the same time
continue to actually focus ourorganization to make the right
bets on the pipeline and get themarket also ready for those.
(53:03):
Those are my sort of top ofmind.
In the meantime, we talkedabout scaling.
Look, the way I see it is.
We're building skyscrapers notjust one skyscraper, that's TTR.
Another skyscraper is the rare,but the many things can come in
neurological disorders and soforth.
What I want to make sure isthat the foundation that we're
(53:24):
building in the commercialorganization can apply to each
of those skyscrapers.
So that's certain foundationalcapabilities like AI, like how
do we actually continue togenerate data?
How do we actually build thoseaccess capabilities like
value-based agreements as aconsistent capability?
As a consistent capability, howdo we actually do omni-channel
(53:47):
marketing, so that you know theorganization.
We can focus on realvalue-based activities and
communication on one-on-one,peer-to-peer where it needs to
be and surround sound it withomni-channel capabilities.
These things are no longer pipedreams.
Right, these are actuallythings that we deal with and I
see great practices in ourorganization across the
(54:11):
categories.
But I want to actuallyconsolidate that because
essentially, we're building agenerational biotech.
If you want to build agenerational biotech, you need
to have the right foundations.
Some of my priorities also hasa lot to do with that, but first
and foremost, obviously,winning in TTR is going to be a
key priority and a key test forthe organization.
Ben Comer (54:36):
That is Tolga Tangular, executive Vice
President and Chief CommercialOfficer at Alnylam I'm Ben Comer
and you've just listened to theBusiness of Biotech.
Find us and subscribe anywhereyou listen to podcasts and be
sure to check out new weeklyvideo casts of these
conversations every Monday underthe Business of Biotech tab at
Life Science Leader.
(54:56):
We'll see you next week andthanks for listening.
Avantor is a leading lifescience tools company and global
provider of mission-criticalproducts and services to the
life sciences and advancedtechnology industries.
Avantor works side-by-side withcustomers at every step of the
scientific journey to enablebreakthroughs in medicine,
(55:17):
healthcare and technology.
Avantor's portfolio is used invirtually every stage of the
most important research,development and production
activities at more than 300,000customer locations in 180
countries.
For more information, visitavantorsciences.
com or find them on LinkedIn,ex-formerly Twitter and Facebook
(55:40):
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