November 17, 2025 • 36 mins
Richard Pazdur took the top job at FDA’s Center for Drug Evaluation and Research after receiving vows that he would be leading CDER free from political interference. On the latest BioCentury This Week podcast, BioCentury's analysts discuss the issues that could prove to be flashpoints between Pazdur and the heads of FDA and HHS, including personnel, RSV mAbs, puberty blockers and SSRIs.
BioCentury's analysts assess bispecific innovation at the annual meeting of the Society for Immunotherapy of Cancer (SITC) and the growing field of companies pursuing RNAi, many of which have multiple unpartnered assets. Also featured in this week's episode: new funds from European VCs Medicxi and Sofinnova Partners, FDA’s new plausible mechanism pathway and the Trump administration’s “most favored nation” drug-pricing plan, which is turning out to be much more less onerous to drug companies than its original description suggested. This episode of the BioCentury This Week podcast is brought to you by Voyager Therapeutics.
View full story: https://www.biocentury.com/article/657631
#RNAiTherapeutics #BispecificAntibodies #CD3TCellEngagers #MechanismOfAction #ImmunoOncology #PlausibleMechanismPathway #RegulatoryScience #ClinicalTranslation
00:01 - Sponsor Message: Voyager Therapeutics
03:08 - FDA's Richard Pazdur
13:08 - Plausible Mechanism Pathway
19:30 - Most Favored Nation
23:12 - Takeaways from SITC
28:05 - RNAi in China
33:21 - European VCs
To submit a question to BioCentury’s editors, email the BioCentury This Week team at podcasts@biocentury.com.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
[AI-generated transcript.]
Eric Pierce (00:02):
BioCentury This Week is brought to you
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Voyager addresses the challengeof delivering novel treatments
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The company's programs addressdiseases with substantial unmet
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Jeff Cranmer (00:50):
Richard Pazdur took the top job at FDA's CDER
after initially turning it down.
Why is he the rightperson for the job?
What is he likely to tryto get done and what are
some of the potential flashpoints with FDA Commissioner,
Makary and RFK Jr.?
(01:12):
Also on the BioCentury thisweek podcast, we have the
latest on MFN, why the mostFavored nation scheme is less
onerous than some thought.
And FDA's new plausiblemechanism pathway.
Plus, as promised, we'llhave our colleague, Lauren
Mart's takeaways fromthis year's SITC Meeting.
(01:33):
that's the Society forImmunotherapy of Cancer, for
those keeping score at home.
And why China's RNA therapiesare in growing demand.
And we'll take a quick lookat two new funds from two
of Europe's leading VCs.
I'm Jeff Cranmer, executiveeditor here at BioCentury, and
(01:57):
I'm joined by my colleagues.
Steve Usdin (01:59):
Steve Usdin, Washington Editor.
Lauren Martz (02:01):
Lauren Martz, Executive Director of
Biopharma Intelligence.
Selina Koch (02:05):
And Selina Koch, executive editor.
Jeff Cranmer (02:08):
Okay, well it's London Life Sciences Week.
Some just call itJefferies for short.
Like to give a shout out toeveryone who is in London
for the event madly dashingabout and setting up meetings.
Our colleagues, Simone,Stephen, and Josh are there.
They'll be recording a SpecialEdition of the BioCentury's
(02:30):
This Week podcast, taking itOn the Road at the 3rd Biotech
CEO and Investor Reception thatwe put on with BIA, Pioneer,
and Precision Biosearch.
The event is sold out.
It's on Wednesday, I believeyou can join the wait list
on our website if you like.
(02:50):
That is one of twoupcoming Special Episodes
of the BioCentury's ThisWeek podcast this week.
The other will feature aconversation with Al Sandrock,
CEO of Voyager, he is alsothe former CMO of Biogen.
All righty, Steve.
So Pazdur changed his mindand took the top job at CDER.
(03:14):
After all.
Why?
Steve Usdin (03:15):
Well look, it has been a long week.
So last week you're right,yeah the news was that Richard
Pazdur, Director of the OncologyCenter of Excellence, had
turned down an opportunityto become Director of CDER.
Then on Tuesday, he accepted thejob based on commitments from
HHS Secretary Kennedy and FDACommissioner Makary, that he
(03:36):
and CDER would not be subjectto political interference.
I usually think it's silly whenpeople thank someone for taking
a prestigious job in government.
In this case, I think theappreciation expressed
by patient advocates, FDAemployees and biopharma
executives is genuine.
It really is difficult toimagine anyone who will
be better as CDER directorright now than Rick Pazdur.
(03:59):
In my story about hisappointment, I wrote that
he represents stability ata moment when public health
institutions are under strainand integrity at a time
when regulatory decisionshave become politicized.
In over a quarter centuryat FDA Pazdur and the
teams he's led have builtregulatory frameworks that
have made possible precisionMedicxines, immunotherapies,
and other drug classes thattransformed cancer care.
(04:21):
I think that people arelooking to him and hoping
that he can do somethingsimilar for CDER writ large.
Jeff Cranmer (04:27):
Steve, what do you think he's
likely to try to achieve?
Steve Usdin (04:31):
Well first I, I think having, praised him
so much, I have to make itvery clear, he's very likely
to make decisions that somepeople who are listening
to this podcast don't like.
He's never been afraidto ruffle feathers.
He is very outspoken in hisviews, and very surefooted
when he thinks somethingis the right thing to do.
So, a few things I'veobserved about him that I
(04:53):
think suggest what he'll do.
First, he recruits and heretains and he supports
really excellent people.
You know, a quick storyabout that years ago, and
a few less gray hairs.
I hosted a TV show that wason old fashioned broadcast tv.
I invited Pazdur and I asked himto suggest someone to accompany
him on the show, and I said,we can invite anyone he wanted.
(05:16):
I suggested someprominent scientists,
some government leaders.
He didn't miss a beat.
He immediately said he wantedto bring four of his staffers
on, and he said they don't getenough recognition for what they
do, that's what he wanted to do.
That's the kind of movethat instills a great
deal of loyalty among thepeople who he's recruited.
So what's he gonna do?
(05:36):
I think bolsteringmorale at CDER is gonna
be his first priority.
Hiring staff, including somewho were pushed out or quit
this year is likely to be next.
I think he's gonna try toemulate the Oncology Center
of Excellence by creatingways for CDER, CBER,
and CDRH to collaboratemuch more closely around
specific clinical areas likecardiovascular and neurology.
(05:58):
Vinay Prasad, the Directorof CBER, mentioned that,
in a recent, um, webcastwith Commissioner Makary.
And I think he's gonnaempower and support his staff.
Pazdur's not gonna interveneto overturn regulatory
decisions that he doesn't like.
He's been critical of senatedirectors who've done that in
the past, and I don't thinkhe's gonna do that himself.
Jeff Cranmer (06:19):
We published his letter to staff, which
I thought was really cool.
Do you wanna speakto that a little bit?
Steve Usdin (06:25):
Yeah.
Um, it, it reallywas in his voice.
I, I really encouragepeople to, read it.
as you said, we,we ran it in full.
He didn't try tosugarcoat things.
He acknowledged that therehave been challenges that
things have been, um, reallydifficult over the last year.
He said he's experienced,some of the same feelings
that other CDER staff have.
And he said, you know,look, it's time to move
(06:47):
on, we're gonna move, moveforward, and try to bring
some stability to it.
He accompanied the letter witha photograph of him standing
next to an open door and atthe end of the letter he said
something to the effect of,you know, my door's always
open, I'm gonna try to makemyself accessible to staff
so you can come in and talkto me, if you have concerns.
So it was really kindof vintage Rick Pazdur.
Jeff Cranmer (07:09):
So about the, uh, the heat shield, the
promise is not to meddle.
What are some of the potentialflashpoint, that he might
have with Makary and RFK Jrand maybe even Vinay Prasad?
Steve Usdin (07:23):
Or President Trump.
Look, it's, it's impossible.
This administrationnever ceases to amaze.
So, I really couldn'tpredict with certainty the.
But here's some things thatare, that are possible, right?
So Kennedy and Makary haveset in motion a number of
initiatives that I thinkcould put their commitment to
avoid political interferencewith CDER to the test.
(07:45):
Makary has centralized power inthe Office of the Commissioner,
and he's tasked politicalappointees in his office with
reviewing products that areimportant to the Maha agenda.
He started with vaccines, andthe Office of the Commissioner
led initiatives that resultedin changes to vaccine regulation
(08:06):
that were really at oddswith what CBER staff thought
was the correct thing to do.
Right now there are reviewsgoing on in the Office of
the Commissioner that couldaffect CDER products, reviews
of puberty blockers, SSRIs forchildren and adolescents, and
monoclonal antibodies for RSV.
Some of those have beensubject to expert review
(08:27):
panels that Makary has held.
Others have been discussed inthe MAHA report, and elsewhere.
So, if Makary tries to dictatepolicies on these circumventing
CDER reviewers and staff,I think that could create
issues, for Rick Pazdur.
Another possible FlashpointMakary has interviewed
(08:49):
candidates for jobs at CDER.
if he tries to push out CDERstaff and replace them with
people he selects, that couldalso create a lot of tension.
So those are things thatwere underway before
Dr. Pazdur took the job.
And it's gonna be reallyinteresting to see if
they continue and how,how they get resolved.
(09:10):
There's also an issue of howCDER's going to implement
some of the policies thatDr. Makary has put in place.
One of them is theCommissioner's National
Priority Voucher.
The way that Makary hasdescribed that process kind
of sidesteps a lot of theprocesses that CDER and CBER,
(09:31):
have put in place over theyears that are intended.
To ensure kind of due diligenceabout reviews, but also they're
intended to allow individualreviewers, scientists at
FDA to speak up and expressconcerns that they might have
and kind of like creates asafe space for them to do that.
Um, the CNPV seems to makethat much less likely,
(09:54):
much more difficult.
There are also issues overwho's gonna actually sign the
approval letters for drugsthat are approved or products
that are approved, thatreceive CNPV's, so we'll see
how Dr. Pazdur navigates that.
And then finally there's thePlausible Mechanism Pathway.
I think we're gonna talkabout that later on the show.
And you know, I think thatthere likely, there are other
(10:17):
kind of high profile decisions,policies that Commissioner
Makary, CBER, Director Prasadare working on that are
intended to advance theirderegulatory agenda at FDA.
And those, because theykind of disrupt the status
quo, it will be importantfor there success for them
(10:38):
to have the CDER Director,kind of on board with them.
Selina Koch (10:42):
So Steve, I, I, feel like one of the things
is known for in oncology isbringing some coherence, some
standardization to the policiesand processes around accelerated
approval, which has been gamechanging in that disease area.
But when you just have onedisease area like that and, and
one that's has a certain amountof consistency, right, like
(11:03):
most of the time, you know whatthe problem is, it's the tumor.
Therefore, if you can shrinkthe tumor, that should be a good
thing, you know, and you couldbuild a system around that.
I know there's controversy abouthow well that does translate
into overall survival andwhatnot, but it's, it makes
sense at a foundational level.
when you think about doingthe same sort of thing across
(11:24):
indications, all the thingsthat CDER looks at, and
then all the other stuff hehas to deal with right now.
Is there any chance of himbeing able to make some
progress on bringing someconsistency to accelerated
approval broadly beyond cancer?
Steve Usdin (11:39):
You know, I don't have any inside.
Information about that, butit wouldn't surprise me if
that was a priority of his.
And given the way that he isoperated at OCE, my guess is it
is not like he's going to tryto dictate answers from the top
and say, okay, well this is,this is how we're gonna do it.
He tends to have a much morecollaborative approach to
(12:00):
things, and my guess would bethat at some point down the
line, he would bring togetherpeople from CBER, from CDER.
Again, maybe even from CDRHwhen it's appropriate and
try to create those kind of,that kind of consistency.
He's got an awful lot of otherthings to worry about right now.
I think first you know, it'sreally necessary to kind
(12:21):
of right the ship becausethere really has been, and
still is, there's an ongoingcrisis in morale, and in
consistency and in theability to meet the basic.
Things that, um, CDERhas to do, you know, to
kind of like keeping thelights on, keeping the ship
moving forward, whateveranalogy you want to use.
(12:42):
So I think that's gonna haveto be the first priority.
But I would imagine thingslike accelerated approval
will come down the road.
I think that you, you'realso likely to see a push
for, um, more transparencyand accountability in the
form of advisory committees.
You maybe remember that underCommissioner Califf, there
was a big controversy atFDA over how to reform the
(13:07):
advisory committee process.
And there was a disputebetween some people at FDA
who wanted to eliminate orscale back the use of voting
by advisory committees.
And Dr. Pazdur was verymuch on the side of
wanting to retain voting.
He thinks that it leadsto more clarity about
what the decisions are.
(13:27):
I know that there's somein industry who take a very
different, view from that,but I, I think that one of the
marks that we'll see of whetherhe's able to, able to kind of
bring CDER back to a trajectorythat's more like what it was
on before January, will be hisability to ramp up advisory
committee meetings and otherkinds of forums where there's
(13:49):
public accountability andtransparency around things like
endpoints for specific diseases.
And that would flow into theAccelerated Approval to be.
Jeff Cranmer (13:58):
Alright, Steve, will you tease the
Plausible Mechanism storywhich you wrote last week,
this new pathway at FDA, andI've gotta say it inspired
you to become a politicalcartoonist and I'm impressed.
What can I say?
Uh, I didn't know youwere an artist, Steve.
Steve Usdin (14:16):
Well, I get, I do get a little assistance
from ChatGPT on that, but,um, and that, that was
like a little silly thing.
It's on LinkedIn.
But basically, the storythat I wrote about the
Plausible Mechanism Pathway,it's kind of two parts.
It's a little complicated.
I think that a lot of peoplein the rare disease community
especially really applaudthis and they really look
(14:37):
forward to FDA defining a newpathway that's going to be
science-based and rigorous.
And that's gonna allow forthe approval and facilitate
the development of drugsfor rare and especially
for ultra rare diseases.
And to that extent, Ithink people are really
happy with, with theplausible mechanism pathway.
(14:59):
On the other hand, the paperthat was written in the New
England Journal of Medicxineannouncing it is very vague.
It's short on a lot of details.
There's no process in there.
And that's led some people tobe very concerned about whether
this is really going to happenand if it happens, if it's
gonna happen in a predictablefair way that gives companies
(15:22):
the the kind of assurancesthat they need to invest in the
development of these productsand gives patients the sense
that, they're going to be ableto kind of participate in this
process really to lead it asI think that they should be.
Now you mentioned my cartoon,my cartoon really was pointing
out that I think that FDA,Commissioner Makary haven't
(15:44):
done themselves any favorby calling this pathway the
plausible mechanism pathway,the idea of plausible, it's
just a really unfortunate word.
I mean, can you imaginea patient going into a
physician and being told,here's a, a drug for you.
I think you should take it.
FDA says it's plausible.
It also gives payers aneasy way to avoid covering
(16:09):
products, or leverage fortrying to reduce the payment
for products by saying, well,the, these products are not
as safe and effective, thestandards for approving them
weren't um as high as theyare for other products, FDA
just says they're plausible.
So again, I think if this isdone properly, the science
behind it, the certainty aroundit, should be very high because
(16:33):
what they're talking about doingis intervening in basic, the
basic fundamental biologicalpathways that create disease.
And then being able to seechanges, to be able to see halts
and progression, maybe in somecases even reversals, so that
Selina Koch (16:50):
Yeah.
This comes down tocausal biology, really.
Right?
Like if you know whatthe cause of biology is.
If you understand the diseaseand then you intervene in
a very sort of direct way,maybe they should call it
the root cause pathway.
What do you think, Steve?
Steve Usdin (17:03):
That would be a good name!
Or the, or the causal biologyor the what, whatever, you
know, something, somethingthat expresses the idea that
this, this is something that'sactually based on applying
science in a way that didn'texist when the standards, the
standard methods that FDA usesthe empirical methods, you know,
a placebo controlled trial ortwo placebo controlled trials,
(17:24):
running them and just seeingwhat happens, and then making
a decision based on that.
This is based on sciencethat didn't exist when those
standards were created.
I think the other thing that'sgonna be really important is
creating the right guardrailsaround it for things that,
where it is possible, andpreferable to run randomized
controlled trials, the companiesstill are required to do that.
(17:47):
The other thing of courseis important is to have
really rigorous collectionof outcomes data and then,
adjusting approvals basedon that data that comes out.
Selina Koch (17:57):
Steve, is this just for programs that have
indications smaller thanlike a thousand patients,
is there a cutoff like that?
Steve Usdin (18:05):
No, they specifically say in the New
England Journal of Medicxinepiece that, um, well, it's,
it's really the examples thatthey give, you know, Baby
KJ, the N-of-one therapy,and they talk about bespoke
therapies, but they also say,you know, that this pathway
in the future could be appliedto more common diseases.
(18:27):
That's again, somethingthat's gonna have to really
be explained in guidance.
They've said, that there's goingto be joint CDER CBER guidance
on how this is implemented.
And I think a lot of peopleare gonna be really, really
very interested in seeing howthat guidance is developed
and hopefully the FDA willalso find ways to allow the
(18:48):
patient advocates and scientistsfrom companies and scientists
from academia to have theirvoices heard in the way that
FDA develops that guidance.
Selina Koch (18:59):
Yeah, I'm keenly interested in that because I
think we all recently saw whathappened to uniQure, right?
So Huntington's disease,that's monogenic.
We understand the causalbiology, the therapy intervenes
in the causal biologycompany was said it could
use it and it's very rare.
It's not quite n-of-oneultra rare, but it's rare.
(19:19):
But was told it could use, anatural history comparator, and
then it was told it couldn't.
So I feel like everybody's justsort of like a little bit on
the edge of their seats beinglike, but, there's these mixed
messages coming out and what'sit actually gonna be, you know?
Steve Usdin (19:32):
I agree.
And the, the real question is,are they gonna walk the talk?
You know, are theyactually going to do this.
The thinking behind theplausible mechanism pathway,
leaving aside the terriblename is something that I
think that a lot of peoplereally would applaud.
And it is actuallyconsistent with what's
happening internationally.
I've had extensive discussionsrecently, with people in the
(19:53):
U.K. about a similar conceptthat they're developing, and
I'm gonna write about that soon.
The kind of thinking aroundthe world is converging along
similar lines, the importantthing will be the nitty
gritty details of how it'sactually put into practice.
Jeff Cranmer (20:10):
All right, Steve, quickly, MFN you,
uh, you wrote that it turnsout that it may be a little
less onerous than, uh, oncethought, quick thoughts there?
Steve Usdin (20:19):
Yeah.
So when President Trump,and uh other members of his
administration first talkedabout MFN months ago, they
said the United States wasgonna get the lowest price
for drugs paid anywhere inthe industrialized world.
There were legions ofconsultants that went out
and started doing, you know,running their spreadsheets
(20:41):
showing what us priceswould be like if they were
pegged against, for example,Luxembourg, or South Korea, or
Greece or something like that.
And those would be reallyenormous drops in US prices.
But it turns out, that it seemsto be what the administration
is talking about now is thesecond lowest price among
(21:03):
the G7 leaving out the USand Denmark and Switzerland.
That is a much more generoustarget or benchmark than
just saying it's gonnabe the lowest among all
industrialized countries.
There isn't that big a gapbetween the first, the
most expensive in the G7plus Denmark and Switzerland
(21:24):
compared to the number two,that isn't really the issue.
It's really the issueis limiting it to those
countries and leavingout other industrialized
countries that have much morestringent price controls.
Jeff Cranmer (21:36):
All right, and Steve story on MFN on the
plausible mechanism up online.
And, you also have, uh, hislatest in a series of stories
uh about the bouncing ballthat has been Dr. Pazdur
over the past 10 days or so.
We're gonna take a quick breakand we'll return to talk SITC.
Alanna Farro (21:58):
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Jeff Cranmer (22:46):
Okay.
And East-West, I have startedrecruiting Presenting Companies
to appear at the conference.
If you're interested, dropme a line on LinkedIn.
And we aren't just lookingfor Korean companies.
We'll have a good group ofKorean companies for sure, but
we'd love to get some Westerncompanies, some companies
(23:06):
from Japan, China, Australia.
So if you'd like tolearn more, reach on out.
Lauren, let's draw youinto the conversation here.
You took a close look atBispecifics in your analysis
of abstracts out of this year'sSociety for Immunotherapy
of Cancer annual meeting.
(23:27):
why'd you choosethat to focus on?
Lauren Martz (23:29):
Thanks Jeff.
yeah, so I picked.
Three translationaltrends from the analysis
of the SITC abstracts.
And all three of those are waysto help bispecifics be more
effective against solid tumors.
So this was just something thatcame up over and over again
throughout the abstracts atthis conference, and that's
why I chose to focus there.
So the first one is stromaltargets for bispecifics.
(23:54):
Companies and academic groupshave been attempting to sort
of bring down the tumor stromawith different therapeutic
strategies, uh, for a long time.
And backing up, so the tumorstroma is the fibrotic tissue
that surrounds the tumorand protects it against
immune cells and in somecases against therapeutics.
So this idea that you coulduse a bispecific T cell engager
(24:19):
to target the tumor stromawas relatively new to me.
The idea that we saw in, inseveral abstracts was that these
tumor stroma targets could beused as new ways to sort of
help selectively target a solidtumor, which has been one of the
big challenges in this space.
There aren't a lot of targetsthat can direct the T cells
(24:40):
there and not to healthy organs.
So it's, it's sort ofanother way to attempt that.
And then potentially, bringingthe T cells to these actual
fibroblasts or other typesof cells in the tumor stroma
to try to eliminate themand bring down that barrier.
And then another interestingnote there is that bispecifics
are one way to do that.
There are also some abstractsdescribing CAR T cells that
(25:02):
may do a similar thing, hitthe tumor trauma instead
of tumor antigens andtumor cells themselves.
Selina Koch (25:08):
Are these meant to be combination strategies,
then like if you can use a Tcell engager, get the T cell
to attack the fibroblasts andtake down some of that barrier,
would those same T cells then beable to attack the cancer or do
you need that second component?
Lauren Martz (25:23):
so that leads into the next trend that I saw.
yes.
I think the idea of someof these is a combination.
And in some caseswe're seeing companies
deliver two bispecifics.
Some of them will, you know,one targeting the tumor stroma,
one targeting the tumor itself.
So you could bring T cellsdirected against both of
them at the same time.
The other feature of I thinkat least two of the abstracts
(25:46):
was that one of thosetargeted CD3 on the T cells.
Another targets an alternativecostimulatory receptor on a T
cell, so the idea there is thatyou're providing a T cell with
both of the signals that itneeds for complete activation,
while also, you know, targetingthe tumor, the tumor stroma,
(26:07):
and targeting the tumor.
So that second trendwas alternatives or
additions to CD3.
Most of the bispecific Tcell engagers that we've
seen go through the clinictarget CD3 on T cells, and
they help provide that mainT cell activation signal.
We've started to see some ofthese costimulatory T cells
(26:28):
targeting CD2 or CD28 alsomake their way into the clinic.
And at SITC this year,we're seeing trispecifics or
combinations of bispecifics.
So you know, a trispecifictargets CD3, CD2, for
example, end a tumor antigen.
So you're providing both ofthe signals that a T cell
(26:50):
needs or you're, you know,using two bispecifics to
provide both of those signals.
And that becomes especiallyimportant with solid
tumors because the secondcostimulatory signal comes
from other immune cells inthe tumor microenvironment.
So if it's a cold tumorwith an immunosuppressive
microenvironment, the Tcells may not be getting
(27:11):
that signal and may not bethat effective without this
therapeutic way to provide it.
Jeff Cranmer (27:16):
Good stuff, Lauren.
What, about the third?
Lauren Martz (27:18):
Yeah.
So the third thing I noticed wasan additional class of targets.
These are the glycanand lectin targets.
So glycans are the sugarsthat are expressed on the
surface of cancer cells.
They're modified and theircomposition is altered
in certain ways versusexpression on normal cells.
And then lectins arereceptors that can be
(27:38):
expressed on immune cells.
And when this interactionhappens to connect as a
sort of checkpoint functionand dampen the immune cell
activity against the cancers.
The idea of creating bispecificsthat act as lectin decoys,
that sort of blocked thisinteraction was something
that was presented at SITCand then some other modalities
(27:59):
were also proposed as waysto disrupt this interaction.
Jeff Cranmer (28:03):
All right.
Uh, thanks for that, Lauren.
Let's turn to China'sRNAi therapeutics space.
Recent IPOs and deals out ofChina, biotechs are signaling.
That this is likely the nextmajor modality out of China.
(28:23):
China's expertise inantibody engineering, of
course, as well established.
But, uh, these these earlysigns are suggesting that
the region may soon becomehighly competitive in RNAi.
Lindsay Martin, a new member ofour editorial team, took a look
(28:44):
and Selina edited the piece.
Uh, Selina.
Selina Koch (28:47):
Yeah.
Thanks Jeff.
Well the question we had whenwe dived into this analysis was,
are RNA silencing technologiesbecoming a growing modality
over there, because we hadheard anecdotes, but we hadn't
really dug into the the datain a more systematic way,
so that is what Lindsay did.
And I think what shefound supports that idea.
(29:09):
You know, we've all heard thisphrase, China speed, right?
And usually it's used todescribe how quickly companies
over there can, can get a,a candidate into the clinic.
But her analysis reallyimpressed on me how China
speed really exists on theseother fronts as well, like
the rapid expansion anddiversification of technology
expertise in particular.
(29:30):
Yeah, I mean she just set out toround up RNA silencing programs.
So these are oligo nucleotidesan, you know, antisense oligos
and siRNAs in particular.
Be cause they both try todo the same thing, which is
that they go after a targetby reducing the amount of
that target, by attackingthe it at the RNA level, so
(29:51):
less of it gets produced.
So they have similar functionsand she found, you know,
looking for companies whohave disclosed pipelines of
multiple programs of thesetypes, at least a dozen of them.
And two years ago there wasreally no Dealmaking in these
RNA silencing technologies.
(30:12):
Dealmaking activityright now is still small.
There haven't been a ton ofdisclosed agreements, but in
the last two years there havebeen four that have been sort of
big enough and splashy enough,you know, to be announced in
press releases and whatnot.
And, and, and those four areall worth, in total biobucks,
they're worth north of abillion dollars, their upfronts
range from tens of millionsto a couple hundred million.
Jeff Cranmer (30:36):
and who were the, who were the Western
companies who were firstto kind of seize on this?
Selina Koch (30:42):
Yeah, so those deals, Novartis is
responsible for two of them.
Boehringer Ingelheim for one,and then the, the fourth was
not a, a major pharma, but wasa company called Kalexo Bio.
All four happened tobe for siRNAs and in
either cardiometabolicspaces or in, um, MASH.
(31:02):
And so, that's kind ofthe beginning of what we
expect to be a bigger trend.
She actually found 97siRNA programs over there.
Of which only 11 arepartnered right now.
So hot tip to anyone out therelooking for siRNA programs,
um, a lot of unpartneredprograms coming up in China And
Jeff Cranmer (31:23):
Yeah.
And Lindsay, no doubtwith, Selina's help put
together a great, table.
And just looking at it quickly,the, the names that jump out
at me, uh, Argo, a 4-year-oldcompany, still private, has
over 40 programs, seven are inthe clinic, four are partnered.
Ribo, company out ofSuzhou, they've been around
(31:45):
for, uh, almost 20 years.
They've got a lead in PhaseII, just like Argo, and
they have 18 programs, threeof which are partnered.
And then the other playerthat, you know, tops 10
uh, programs is Anlong Bio,another private company
there, and they have a a dozenprograms, 11 preclinical, and
(32:07):
three of which are partnered.
So this is, uh, a really greattable just to, uh, help you
with your, deal hunting, uh,maybe this week in London,
or, uh, coming up in, uh, whatI assure you will be a very
sunny San Francisco in January.
You can find this storyon BioCenturypodcast.com.
Selina Koch (32:30):
Oh Jeff.
And if I could make one morepoint about this, so Lindsay
then analyzed, all theseprograms by their therapeutic
areas, and this is just offeris like an example, I think
that highlights how far Chinais diversifying beyond cancer.
It's doing that in itsantibodies as well, but here
we have in the RNA programs,a really bolus of them in
(32:52):
cardiovascular, and metabolicand endocrine, and neurology
and a handful of others.
Jeff Cranmer (32:58):
Yeah, well that sort of tracks with what we've
been seeing, uh, in, in Chinadeals and, and the like, right.
A move toward growingexpertise in other areas.
Neurology, especiallyINI, obesity.
Yeah, it's not your, uh,mother's, uh, China anymore.
We're moving beyond oncology.
All right, uh, Selina,thanks for that.
(33:21):
Let's hit up a little financetwo of Europe's most well-known
VCs, Medicxi, and Sofinnovapartners raise new funds as
announced in the past few days.
Sofinnova just overnight.
Uh, our colleague, PaulBonanos, who's the news
editor here at BioCentury.
And follows the venturebeat quite closely.
(33:42):
He caught up with leadersat each firm, Medicxi, is
largely staying the coursewith its new fifth fund.
Paul, found in his conversationwith Giovanni Mariggi.
He found that the firm plansto invest its capital in
attractive assets rather thantechnology development projects
that carry greater risk.
(34:03):
Medicxi's fund five,500 million Euros.
It's the sixth since thefirm broke away from Index
about nine years ago.
Targeting investments in20 to 25 companies, many of
them will be newly created.
And Paul also spoke withSofinnova Partners, Antoine
Papiernik, who sees thefirm's latest and largest
(34:27):
fund, a vote of confidencein European life sciences.
That fund 650 millionEuro, it's about 40% larger
than its predecessor.
As with prior funds, thefirm expects to invest about
70% of it in Europe, inthe balance in US startups.
And that, raise gives thefirm flexibility to build,
(34:50):
more companies with thefund, perhaps as many as 18.
So check out Paul'sstories on BioCentury.com,
BioCentury podcast.com.
Also on BioCentury, Cidara, wow.
Capping a Cinderella year witha $9 billion takeout by Merck.
(35:10):
Plus Lauren took a lookat the new label for a
Sarepta gene therapy.
And as always, if you likewhat you're hearing, like
subscribe, drop us a comment.
We'd love to hear from you.
And, uh, if you see Simone,Josh, or Stephen, uh,
wandering around the streetsof London, give him a shout.
(35:30):
Kendall Square Orchestraprovides the music for
BioCentury's This Week.
The group connects scienceand technology professionals
and other members of thegreater Boston community
to collaborate innovate andinspire through music, while
supporting causes relatedto healthcare and education.
Eric Pierce (35:50):
BioCentury would like to thank Voyager
Therapeutics for supporting theBioCentury This Week podcast.
To learn more aboutVoyager's programs advancing
transformative medicines forneurological diseases, visit
voyagertherapeutics.com.
[AI-generated transcript.]
Eric Pierce (00:02):
BioCentury This Week is brought to you
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Jeff Cranmer (00:50):
Richard Pazdur took the top job at FDA's CDER
after initially turning it down.
Why is he the rightperson for the job?
What is he likely to tryto get done and what are
some of the potential flashpoints with FDA Commissioner,
Makary and RFK Jr.?
(01:12):
Also on the BioCentury thisweek podcast, we have the
latest on MFN, why the mostFavored nation scheme is less
onerous than some thought.
And FDA's new plausiblemechanism pathway.
Plus, as promised, we'llhave our colleague, Lauren
Mart's takeaways fromthis year's SITC Meeting.
(01:33):
that's the Society forImmunotherapy of Cancer, for
those keeping score at home.
And why China's RNA therapiesare in growing demand.
And we'll take a quick lookat two new funds from two
of Europe's leading VCs.
I'm Jeff Cranmer, executiveeditor here at BioCentury, and
(01:57):
I'm joined by my colleagues.
Steve Usdin (01:59):
Steve Usdin, Washington Editor.
Lauren Martz (02:01):
Lauren Martz, Executive Director of
Biopharma Intelligence.
Selina Koch (02:05):
And Selina Koch, executive editor.
Jeff Cranmer (02:08):
Okay, well it's London Life Sciences Week.
Some just call itJefferies for short.
Like to give a shout out toeveryone who is in London
for the event madly dashingabout and setting up meetings.
Our colleagues, Simone,Stephen, and Josh are there.
They'll be recording a SpecialEdition of the BioCentury's
(02:30):
This Week podcast, taking itOn the Road at the 3rd Biotech
CEO and Investor Reception thatwe put on with BIA, Pioneer,
and Precision Biosearch.
The event is sold out.
It's on Wednesday, I believeyou can join the wait list
on our website if you like.
(02:50):
That is one of twoupcoming Special Episodes
of the BioCentury's ThisWeek podcast this week.
The other will feature aconversation with Al Sandrock,
CEO of Voyager, he is alsothe former CMO of Biogen.
All righty, Steve.
So Pazdur changed his mindand took the top job at CDER.
(03:14):
After all.
Why?
Steve Usdin (03:15):
Well look, it has been a long week.
So last week you're right,yeah the news was that Richard
Pazdur, Director of the OncologyCenter of Excellence, had
turned down an opportunityto become Director of CDER.
Then on Tuesday, he accepted thejob based on commitments from
HHS Secretary Kennedy and FDACommissioner Makary, that he
(03:36):
and CDER would not be subjectto political interference.
I usually think it's silly whenpeople thank someone for taking
a prestigious job in government.
In this case, I think theappreciation expressed
by patient advocates, FDAemployees and biopharma
executives is genuine.
It really is difficult toimagine anyone who will
be better as CDER directorright now than Rick Pazdur.
(03:59):
In my story about hisappointment, I wrote that
he represents stability ata moment when public health
institutions are under strainand integrity at a time
when regulatory decisionshave become politicized.
In over a quarter centuryat FDA Pazdur and the
teams he's led have builtregulatory frameworks that
have made possible precisionMedicxines, immunotherapies,
and other drug classes thattransformed cancer care.
(04:21):
I think that people arelooking to him and hoping
that he can do somethingsimilar for CDER writ large.
Jeff Cranmer (04:27):
Steve, what do you think he's
likely to try to achieve?
Steve Usdin (04:31):
Well first I, I think having, praised him
so much, I have to make itvery clear, he's very likely
to make decisions that somepeople who are listening
to this podcast don't like.
He's never been afraidto ruffle feathers.
He is very outspoken in hisviews, and very surefooted
when he thinks somethingis the right thing to do.
So, a few things I'veobserved about him that I
(04:53):
think suggest what he'll do.
First, he recruits and heretains and he supports
really excellent people.
You know, a quick storyabout that years ago, and
a few less gray hairs.
I hosted a TV show that wason old fashioned broadcast tv.
I invited Pazdur and I asked himto suggest someone to accompany
him on the show, and I said,we can invite anyone he wanted.
(05:16):
I suggested someprominent scientists,
some government leaders.
He didn't miss a beat.
He immediately said he wantedto bring four of his staffers
on, and he said they don't getenough recognition for what they
do, that's what he wanted to do.
That's the kind of movethat instills a great
deal of loyalty among thepeople who he's recruited.
So what's he gonna do?
(05:36):
I think bolsteringmorale at CDER is gonna
be his first priority.
Hiring staff, including somewho were pushed out or quit
this year is likely to be next.
I think he's gonna try toemulate the Oncology Center
of Excellence by creatingways for CDER, CBER,
and CDRH to collaboratemuch more closely around
specific clinical areas likecardiovascular and neurology.
(05:58):
Vinay Prasad, the Directorof CBER, mentioned that,
in a recent, um, webcastwith Commissioner Makary.
And I think he's gonnaempower and support his staff.
Pazdur's not gonna interveneto overturn regulatory
decisions that he doesn't like.
He's been critical of senatedirectors who've done that in
the past, and I don't thinkhe's gonna do that himself.
Jeff Cranmer (06:19):
We published his letter to staff, which
I thought was really cool.
Do you wanna speakto that a little bit?
Steve Usdin (06:25):
Yeah.
Um, it, it reallywas in his voice.
I, I really encouragepeople to, read it.
as you said, we,we ran it in full.
He didn't try tosugarcoat things.
He acknowledged that therehave been challenges that
things have been, um, reallydifficult over the last year.
He said he's experienced,some of the same feelings
that other CDER staff have.
And he said, you know,look, it's time to move
(06:47):
on, we're gonna move, moveforward, and try to bring
some stability to it.
He accompanied the letter witha photograph of him standing
next to an open door and atthe end of the letter he said
something to the effect of,you know, my door's always
open, I'm gonna try to makemyself accessible to staff
so you can come in and talkto me, if you have concerns.
So it was really kindof vintage Rick Pazdur.
Jeff Cranmer (07:09):
So about the, uh, the heat shield, the
promise is not to meddle.
What are some of the potentialflashpoint, that he might
have with Makary and RFK Jrand maybe even Vinay Prasad?
Steve Usdin (07:23):
Or President Trump.
Look, it's, it's impossible.
This administrationnever ceases to amaze.
So, I really couldn'tpredict with certainty the.
But here's some things thatare, that are possible, right?
So Kennedy and Makary haveset in motion a number of
initiatives that I thinkcould put their commitment to
avoid political interferencewith CDER to the test.
(07:45):
Makary has centralized power inthe Office of the Commissioner,
and he's tasked politicalappointees in his office with
reviewing products that areimportant to the Maha agenda.
He started with vaccines, andthe Office of the Commissioner
led initiatives that resultedin changes to vaccine regulation
(08:06):
that were really at oddswith what CBER staff thought
was the correct thing to do.
Right now there are reviewsgoing on in the Office of
the Commissioner that couldaffect CDER products, reviews
of puberty blockers, SSRIs forchildren and adolescents, and
monoclonal antibodies for RSV.
Some of those have beensubject to expert review
(08:27):
panels that Makary has held.
Others have been discussed inthe MAHA report, and elsewhere.
So, if Makary tries to dictatepolicies on these circumventing
CDER reviewers and staff,I think that could create
issues, for Rick Pazdur.
Another possible FlashpointMakary has interviewed
(08:49):
candidates for jobs at CDER.
if he tries to push out CDERstaff and replace them with
people he selects, that couldalso create a lot of tension.
So those are things thatwere underway before
Dr. Pazdur took the job.
And it's gonna be reallyinteresting to see if
they continue and how,how they get resolved.
(09:10):
There's also an issue of howCDER's going to implement
some of the policies thatDr. Makary has put in place.
One of them is theCommissioner's National
Priority Voucher.
The way that Makary hasdescribed that process kind
of sidesteps a lot of theprocesses that CDER and CBER,
(09:31):
have put in place over theyears that are intended.
To ensure kind of due diligenceabout reviews, but also they're
intended to allow individualreviewers, scientists at
FDA to speak up and expressconcerns that they might have
and kind of like creates asafe space for them to do that.
Um, the CNPV seems to makethat much less likely,
(09:54):
much more difficult.
There are also issues overwho's gonna actually sign the
approval letters for drugsthat are approved or products
that are approved, thatreceive CNPV's, so we'll see
how Dr. Pazdur navigates that.
And then finally there's thePlausible Mechanism Pathway.
I think we're gonna talkabout that later on the show.
And you know, I think thatthere likely, there are other
(10:17):
kind of high profile decisions,policies that Commissioner
Makary, CBER, Director Prasadare working on that are
intended to advance theirderegulatory agenda at FDA.
And those, because theykind of disrupt the status
quo, it will be importantfor there success for them
(10:38):
to have the CDER Director,kind of on board with them.
Selina Koch (10:42):
So Steve, I, I, feel like one of the things
is known for in oncology isbringing some coherence, some
standardization to the policiesand processes around accelerated
approval, which has been gamechanging in that disease area.
But when you just have onedisease area like that and, and
one that's has a certain amountof consistency, right, like
(11:03):
most of the time, you know whatthe problem is, it's the tumor.
Therefore, if you can shrinkthe tumor, that should be a good
thing, you know, and you couldbuild a system around that.
I know there's controversy abouthow well that does translate
into overall survival andwhatnot, but it's, it makes
sense at a foundational level.
when you think about doingthe same sort of thing across
(11:24):
indications, all the thingsthat CDER looks at, and
then all the other stuff hehas to deal with right now.
Is there any chance of himbeing able to make some
progress on bringing someconsistency to accelerated
approval broadly beyond cancer?
Steve Usdin (11:39):
You know, I don't have any inside.
Information about that, butit wouldn't surprise me if
that was a priority of his.
And given the way that he isoperated at OCE, my guess is it
is not like he's going to tryto dictate answers from the top
and say, okay, well this is,this is how we're gonna do it.
He tends to have a much morecollaborative approach to
(12:00):
things, and my guess would bethat at some point down the
line, he would bring togetherpeople from CBER, from CDER.
Again, maybe even from CDRHwhen it's appropriate and
try to create those kind of,that kind of consistency.
He's got an awful lot of otherthings to worry about right now.
I think first you know, it'sreally necessary to kind
(12:21):
of right the ship becausethere really has been, and
still is, there's an ongoingcrisis in morale, and in
consistency and in theability to meet the basic.
Things that, um, CDERhas to do, you know, to
kind of like keeping thelights on, keeping the ship
moving forward, whateveranalogy you want to use.
(12:42):
So I think that's gonna haveto be the first priority.
But I would imagine thingslike accelerated approval
will come down the road.
I think that you, you'realso likely to see a push
for, um, more transparencyand accountability in the
form of advisory committees.
You maybe remember that underCommissioner Califf, there
was a big controversy atFDA over how to reform the
(13:07):
advisory committee process.
And there was a disputebetween some people at FDA
who wanted to eliminate orscale back the use of voting
by advisory committees.
And Dr. Pazdur was verymuch on the side of
wanting to retain voting.
He thinks that it leadsto more clarity about
what the decisions are.
(13:27):
I know that there's somein industry who take a very
different, view from that,but I, I think that one of the
marks that we'll see of whetherhe's able to, able to kind of
bring CDER back to a trajectorythat's more like what it was
on before January, will be hisability to ramp up advisory
committee meetings and otherkinds of forums where there's
(13:49):
public accountability andtransparency around things like
endpoints for specific diseases.
And that would flow into theAccelerated Approval to be.
Jeff Cranmer (13:58):
Alright, Steve, will you tease the
Plausible Mechanism storywhich you wrote last week,
this new pathway at FDA, andI've gotta say it inspired
you to become a politicalcartoonist and I'm impressed.
What can I say?
Uh, I didn't know youwere an artist, Steve.
Steve Usdin (14:16):
Well, I get, I do get a little assistance
from ChatGPT on that, but,um, and that, that was
like a little silly thing.
It's on LinkedIn.
But basically, the storythat I wrote about the
Plausible Mechanism Pathway,it's kind of two parts.
It's a little complicated.
I think that a lot of peoplein the rare disease community
especially really applaudthis and they really look
(14:37):
forward to FDA defining a newpathway that's going to be
science-based and rigorous.
And that's gonna allow forthe approval and facilitate
the development of drugsfor rare and especially
for ultra rare diseases.
And to that extent, Ithink people are really
happy with, with theplausible mechanism pathway.
(14:59):
On the other hand, the paperthat was written in the New
England Journal of Medicxineannouncing it is very vague.
It's short on a lot of details.
There's no process in there.
And that's led some people tobe very concerned about whether
this is really going to happenand if it happens, if it's
gonna happen in a predictablefair way that gives companies
(15:22):
the the kind of assurancesthat they need to invest in the
development of these productsand gives patients the sense
that, they're going to be ableto kind of participate in this
process really to lead it asI think that they should be.
Now you mentioned my cartoon,my cartoon really was pointing
out that I think that FDA,Commissioner Makary haven't
(15:44):
done themselves any favorby calling this pathway the
plausible mechanism pathway,the idea of plausible, it's
just a really unfortunate word.
I mean, can you imaginea patient going into a
physician and being told,here's a, a drug for you.
I think you should take it.
FDA says it's plausible.
It also gives payers aneasy way to avoid covering
(16:09):
products, or leverage fortrying to reduce the payment
for products by saying, well,the, these products are not
as safe and effective, thestandards for approving them
weren't um as high as theyare for other products, FDA
just says they're plausible.
So again, I think if this isdone properly, the science
behind it, the certainty aroundit, should be very high because
(16:33):
what they're talking about doingis intervening in basic, the
basic fundamental biologicalpathways that create disease.
And then being able to seechanges, to be able to see halts
and progression, maybe in somecases even reversals, so that
Selina Koch (16:50):
Yeah.
This comes down tocausal biology, really.
Right?
Like if you know whatthe cause of biology is.
If you understand the diseaseand then you intervene in
a very sort of direct way,maybe they should call it
the root cause pathway.
What do you think, Steve?
Steve Usdin (17:03):
That would be a good name!
Or the, or the causal biologyor the what, whatever, you
know, something, somethingthat expresses the idea that
this, this is something that'sactually based on applying
science in a way that didn'texist when the standards, the
standard methods that FDA usesthe empirical methods, you know,
a placebo controlled trial ortwo placebo controlled trials,
(17:24):
running them and just seeingwhat happens, and then making
a decision based on that.
This is based on sciencethat didn't exist when those
standards were created.
I think the other thing that'sgonna be really important is
creating the right guardrailsaround it for things that,
where it is possible, andpreferable to run randomized
controlled trials, the companiesstill are required to do that.
(17:47):
The other thing of courseis important is to have
really rigorous collectionof outcomes data and then,
adjusting approvals basedon that data that comes out.
Selina Koch (17:57):
Steve, is this just for programs that have
indications smaller thanlike a thousand patients,
is there a cutoff like that?
Steve Usdin (18:05):
No, they specifically say in the New
England Journal of Medicxinepiece that, um, well, it's,
it's really the examples thatthey give, you know, Baby
KJ, the N-of-one therapy,and they talk about bespoke
therapies, but they also say,you know, that this pathway
in the future could be appliedto more common diseases.
(18:27):
That's again, somethingthat's gonna have to really
be explained in guidance.
They've said, that there's goingto be joint CDER CBER guidance
on how this is implemented.
And I think a lot of peopleare gonna be really, really
very interested in seeing howthat guidance is developed
and hopefully the FDA willalso find ways to allow the
(18:48):
patient advocates and scientistsfrom companies and scientists
from academia to have theirvoices heard in the way that
FDA develops that guidance.
Selina Koch (18:59):
Yeah, I'm keenly interested in that because I
think we all recently saw whathappened to uniQure, right?
So Huntington's disease,that's monogenic.
We understand the causalbiology, the therapy intervenes
in the causal biologycompany was said it could
use it and it's very rare.
It's not quite n-of-oneultra rare, but it's rare.
(19:19):
But was told it could use, anatural history comparator, and
then it was told it couldn't.
So I feel like everybody's justsort of like a little bit on
the edge of their seats beinglike, but, there's these mixed
messages coming out and what'sit actually gonna be, you know?
Steve Usdin (19:32):
I agree.
And the, the real question is,are they gonna walk the talk?
You know, are theyactually going to do this.
The thinking behind theplausible mechanism pathway,
leaving aside the terriblename is something that I
think that a lot of peoplereally would applaud.
And it is actuallyconsistent with what's
happening internationally.
I've had extensive discussionsrecently, with people in the
(19:53):
U.K. about a similar conceptthat they're developing, and
I'm gonna write about that soon.
The kind of thinking aroundthe world is converging along
similar lines, the importantthing will be the nitty
gritty details of how it'sactually put into practice.
Jeff Cranmer (20:10):
All right, Steve, quickly, MFN you,
uh, you wrote that it turnsout that it may be a little
less onerous than, uh, oncethought, quick thoughts there?
Steve Usdin (20:19):
Yeah.
So when President Trump,and uh other members of his
administration first talkedabout MFN months ago, they
said the United States wasgonna get the lowest price
for drugs paid anywhere inthe industrialized world.
There were legions ofconsultants that went out
and started doing, you know,running their spreadsheets
(20:41):
showing what us priceswould be like if they were
pegged against, for example,Luxembourg, or South Korea, or
Greece or something like that.
And those would be reallyenormous drops in US prices.
But it turns out, that it seemsto be what the administration
is talking about now is thesecond lowest price among
(21:03):
the G7 leaving out the USand Denmark and Switzerland.
That is a much more generoustarget or benchmark than
just saying it's gonnabe the lowest among all
industrialized countries.
There isn't that big a gapbetween the first, the
most expensive in the G7plus Denmark and Switzerland
(21:24):
compared to the number two,that isn't really the issue.
It's really the issueis limiting it to those
countries and leavingout other industrialized
countries that have much morestringent price controls.
Jeff Cranmer (21:36):
All right, and Steve story on MFN on the
plausible mechanism up online.
And, you also have, uh, hislatest in a series of stories
uh about the bouncing ballthat has been Dr. Pazdur
over the past 10 days or so.
We're gonna take a quick breakand we'll return to talk SITC.
Alanna Farro (21:58):
BioCentury This Week is brought to you by
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Jeff Cranmer (22:46):
Okay.
And East-West, I have startedrecruiting Presenting Companies
to appear at the conference.
If you're interested, dropme a line on LinkedIn.
And we aren't just lookingfor Korean companies.
We'll have a good group ofKorean companies for sure, but
we'd love to get some Westerncompanies, some companies
(23:06):
from Japan, China, Australia.
So if you'd like tolearn more, reach on out.
Lauren, let's draw youinto the conversation here.
You took a close look atBispecifics in your analysis
of abstracts out of this year'sSociety for Immunotherapy
of Cancer annual meeting.
(23:27):
why'd you choosethat to focus on?
Lauren Martz (23:29):
Thanks Jeff.
yeah, so I picked.
Three translationaltrends from the analysis
of the SITC abstracts.
And all three of those are waysto help bispecifics be more
effective against solid tumors.
So this was just something thatcame up over and over again
throughout the abstracts atthis conference, and that's
why I chose to focus there.
So the first one is stromaltargets for bispecifics.
(23:54):
Companies and academic groupshave been attempting to sort
of bring down the tumor stromawith different therapeutic
strategies, uh, for a long time.
And backing up, so the tumorstroma is the fibrotic tissue
that surrounds the tumorand protects it against
immune cells and in somecases against therapeutics.
So this idea that you coulduse a bispecific T cell engager
(24:19):
to target the tumor stromawas relatively new to me.
The idea that we saw in, inseveral abstracts was that these
tumor stroma targets could beused as new ways to sort of
help selectively target a solidtumor, which has been one of the
big challenges in this space.
There aren't a lot of targetsthat can direct the T cells
(24:40):
there and not to healthy organs.
So it's, it's sort ofanother way to attempt that.
And then potentially, bringingthe T cells to these actual
fibroblasts or other typesof cells in the tumor stroma
to try to eliminate themand bring down that barrier.
And then another interestingnote there is that bispecifics
are one way to do that.
There are also some abstractsdescribing CAR T cells that
(25:02):
may do a similar thing, hitthe tumor trauma instead
of tumor antigens andtumor cells themselves.
Selina Koch (25:08):
Are these meant to be combination strategies,
then like if you can use a Tcell engager, get the T cell
to attack the fibroblasts andtake down some of that barrier,
would those same T cells then beable to attack the cancer or do
you need that second component?
Lauren Martz (25:23):
so that leads into the next trend that I saw.
yes.
I think the idea of someof these is a combination.
And in some caseswe're seeing companies
deliver two bispecifics.
Some of them will, you know,one targeting the tumor stroma,
one targeting the tumor itself.
So you could bring T cellsdirected against both of
them at the same time.
The other feature of I thinkat least two of the abstracts
(25:46):
was that one of thosetargeted CD3 on the T cells.
Another targets an alternativecostimulatory receptor on a T
cell, so the idea there is thatyou're providing a T cell with
both of the signals that itneeds for complete activation,
while also, you know, targetingthe tumor, the tumor stroma,
(26:07):
and targeting the tumor.
So that second trendwas alternatives or
additions to CD3.
Most of the bispecific Tcell engagers that we've
seen go through the clinictarget CD3 on T cells, and
they help provide that mainT cell activation signal.
We've started to see some ofthese costimulatory T cells
(26:28):
targeting CD2 or CD28 alsomake their way into the clinic.
And at SITC this year,we're seeing trispecifics or
combinations of bispecifics.
So you know, a trispecifictargets CD3, CD2, for
example, end a tumor antigen.
So you're providing both ofthe signals that a T cell
(26:50):
needs or you're, you know,using two bispecifics to
provide both of those signals.
And that becomes especiallyimportant with solid
tumors because the secondcostimulatory signal comes
from other immune cells inthe tumor microenvironment.
So if it's a cold tumorwith an immunosuppressive
microenvironment, the Tcells may not be getting
(27:11):
that signal and may not bethat effective without this
therapeutic way to provide it.
Jeff Cranmer (27:16):
Good stuff, Lauren.
What, about the third?
Lauren Martz (27:18):
Yeah.
So the third thing I noticed wasan additional class of targets.
These are the glycanand lectin targets.
So glycans are the sugarsthat are expressed on the
surface of cancer cells.
They're modified and theircomposition is altered
in certain ways versusexpression on normal cells.
And then lectins arereceptors that can be
(27:38):
expressed on immune cells.
And when this interactionhappens to connect as a
sort of checkpoint functionand dampen the immune cell
activity against the cancers.
The idea of creating bispecificsthat act as lectin decoys,
that sort of blocked thisinteraction was something
that was presented at SITCand then some other modalities
(27:59):
were also proposed as waysto disrupt this interaction.
Jeff Cranmer (28:03):
All right.
Uh, thanks for that, Lauren.
Let's turn to China'sRNAi therapeutics space.
Recent IPOs and deals out ofChina, biotechs are signaling.
That this is likely the nextmajor modality out of China.
(28:23):
China's expertise inantibody engineering, of
course, as well established.
But, uh, these these earlysigns are suggesting that
the region may soon becomehighly competitive in RNAi.
Lindsay Martin, a new member ofour editorial team, took a look
(28:44):
and Selina edited the piece.
Uh, Selina.
Selina Koch (28:47):
Yeah.
Thanks Jeff.
Well the question we had whenwe dived into this analysis was,
are RNA silencing technologiesbecoming a growing modality
over there, because we hadheard anecdotes, but we hadn't
really dug into the the datain a more systematic way,
so that is what Lindsay did.
And I think what shefound supports that idea.
(29:09):
You know, we've all heard thisphrase, China speed, right?
And usually it's used todescribe how quickly companies
over there can, can get a,a candidate into the clinic.
But her analysis reallyimpressed on me how China
speed really exists on theseother fronts as well, like
the rapid expansion anddiversification of technology
expertise in particular.
(29:30):
Yeah, I mean she just set out toround up RNA silencing programs.
So these are oligo nucleotidesan, you know, antisense oligos
and siRNAs in particular.
Be cause they both try todo the same thing, which is
that they go after a targetby reducing the amount of
that target, by attackingthe it at the RNA level, so
(29:51):
less of it gets produced.
So they have similar functionsand she found, you know,
looking for companies whohave disclosed pipelines of
multiple programs of thesetypes, at least a dozen of them.
And two years ago there wasreally no Dealmaking in these
RNA silencing technologies.
(30:12):
Dealmaking activityright now is still small.
There haven't been a ton ofdisclosed agreements, but in
the last two years there havebeen four that have been sort of
big enough and splashy enough,you know, to be announced in
press releases and whatnot.
And, and, and those four areall worth, in total biobucks,
they're worth north of abillion dollars, their upfronts
range from tens of millionsto a couple hundred million.
Jeff Cranmer (30:36):
and who were the, who were the Western
companies who were firstto kind of seize on this?
Selina Koch (30:42):
Yeah, so those deals, Novartis is
responsible for two of them.
Boehringer Ingelheim for one,and then the, the fourth was
not a, a major pharma, but wasa company called Kalexo Bio.
All four happened tobe for siRNAs and in
either cardiometabolicspaces or in, um, MASH.
(31:02):
And so, that's kind ofthe beginning of what we
expect to be a bigger trend.
She actually found 97siRNA programs over there.
Of which only 11 arepartnered right now.
So hot tip to anyone out therelooking for siRNA programs,
um, a lot of unpartneredprograms coming up in China And
Jeff Cranmer (31:23):
Yeah.
And Lindsay, no doubtwith, Selina's help put
together a great, table.
And just looking at it quickly,the, the names that jump out
at me, uh, Argo, a 4-year-oldcompany, still private, has
over 40 programs, seven are inthe clinic, four are partnered.
Ribo, company out ofSuzhou, they've been around
(31:45):
for, uh, almost 20 years.
They've got a lead in PhaseII, just like Argo, and
they have 18 programs, threeof which are partnered.
And then the other playerthat, you know, tops 10
uh, programs is Anlong Bio,another private company
there, and they have a a dozenprograms, 11 preclinical, and
(32:07):
three of which are partnered.
So this is, uh, a really greattable just to, uh, help you
with your, deal hunting, uh,maybe this week in London,
or, uh, coming up in, uh, whatI assure you will be a very
sunny San Francisco in January.
You can find this storyon BioCenturypodcast.com.
Selina Koch (32:30):
Oh Jeff.
And if I could make one morepoint about this, so Lindsay
then analyzed, all theseprograms by their therapeutic
areas, and this is just offeris like an example, I think
that highlights how far Chinais diversifying beyond cancer.
It's doing that in itsantibodies as well, but here
we have in the RNA programs,a really bolus of them in
(32:52):
cardiovascular, and metabolicand endocrine, and neurology
and a handful of others.
Jeff Cranmer (32:58):
Yeah, well that sort of tracks with what we've
been seeing, uh, in, in Chinadeals and, and the like, right.
A move toward growingexpertise in other areas.
Neurology, especiallyINI, obesity.
Yeah, it's not your, uh,mother's, uh, China anymore.
We're moving beyond oncology.
All right, uh, Selina,thanks for that.
(33:21):
Let's hit up a little financetwo of Europe's most well-known
VCs, Medicxi, and Sofinnovapartners raise new funds as
announced in the past few days.
Sofinnova just overnight.
Uh, our colleague, PaulBonanos, who's the news
editor here at BioCentury.
And follows the venturebeat quite closely.
(33:42):
He caught up with leadersat each firm, Medicxi, is
largely staying the coursewith its new fifth fund.
Paul, found in his conversationwith Giovanni Mariggi.
He found that the firm plansto invest its capital in
attractive assets rather thantechnology development projects
that carry greater risk.
(34:03):
Medicxi's fund five,500 million Euros.
It's the sixth since thefirm broke away from Index
about nine years ago.
Targeting investments in20 to 25 companies, many of
them will be newly created.
And Paul also spoke withSofinnova Partners, Antoine
Papiernik, who sees thefirm's latest and largest
(34:27):
fund, a vote of confidencein European life sciences.
That fund 650 millionEuro, it's about 40% larger
than its predecessor.
As with prior funds, thefirm expects to invest about
70% of it in Europe, inthe balance in US startups.
And that, raise gives thefirm flexibility to build,
(34:50):
more companies with thefund, perhaps as many as 18.
So check out Paul'sstories on BioCentury.com,
BioCentury podcast.com.
Also on BioCentury, Cidara, wow.
Capping a Cinderella year witha $9 billion takeout by Merck.
(35:10):
Plus Lauren took a lookat the new label for a
Sarepta gene therapy.
And as always, if you likewhat you're hearing, like
subscribe, drop us a comment.
We'd love to hear from you.
And, uh, if you see Simone,Josh, or Stephen, uh,
wandering around the streetsof London, give him a shout.
(35:30):
Kendall Square Orchestraprovides the music for
BioCentury's This Week.
The group connects scienceand technology professionals
and other members of thegreater Boston community
to collaborate innovate andinspire through music, while
supporting causes relatedto healthcare and education.
Eric Pierce (35:50):
BioCentury would like to thank Voyager
Therapeutics for supporting theBioCentury This Week podcast.
To learn more aboutVoyager's programs advancing
transformative medicines forneurological diseases, visit
voyagertherapeutics.com.
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