December 8, 2025 • 35 mins
Fueled by cancer, obesity and cardiovascular deals, $1 billion-plus takeouts in biotech are at their highest level in a decade with three weeks to go in the year. On the latest BioCentury This Week, BioCentury’s analysts discuss the rise in large M&A deals and what the trends among the 37 acquisitions say about biopharma dealmaking.
The analysts assess first-in-human in vivo CAR T data at the American Society of Hematology meeting from Kelonia Therapeutics, which showcase the promise of the modality and justify the growing pipeline. They also break down readouts from Praxis in developmental and epileptic encephalopathy from the American Epilepsy Society Annual Meeting and from Novo Nordisk, which presented full data at the Clinical Trials on Alzheimer’s Disease meeting on semaglutide’s failure to treat Alzheimer’s disease.
Washington Editor Steve Usdin analyzes a roller-coaster week at FDA in which Richard Pazdur resigned as director of FDA’s Center for Drug Evaluation and Research and Tracy Beth Høeg became acting CDER director, a move that Usdin says will prompt staff departures, ease restraints on FDA leaders
View full story: https://www.biocentury.com/article/657781
#BiotechMA #CARTTherapy #EpilepsyResearch #AlzheimersDisease #FDA
02:37 - Biotech M&A
06:39 - In vivo CAR T
10:08 - Semaglutide for Alzheimer's
16:17 - Praxis
22:11 - FDA
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.]
Jeff Cranmer (00:01):
Fueled by cancer, obesity, and cardiovascular
deals billion dollar plustakeouts in biotech are
on the rise, we'll take acloser look on the latest
BioCentury's This Week podcast.
Plus, welcome to ASH Monday,data have been pouring out of
(00:21):
Orlando from the HematologySociety's Annual Meeting, we'll
zero in on first-in-human invivo CAR T data from Kelonia.
And more data, anotherPraxis win provides
much needed progress inrare genetic epilepsies.
And Selina got that datashe was looking for the full
(00:44):
data set for semaglutide,uh, presented at CTAD,
semaglutide was supposedto quench CNS inflammation,
it didn't, Selina will diginto the details for you.
And another tumultuousweek at FDA, Steve will
give his analysis on theback half of the podcast.
(01:06):
I'm Jeff Cranmer, one ofthe executive editors here
at BioCentury, and joiningme today are my colleagues.
Simone Fishburn (01:13):
Simon Fishburn, Editor in Chief.
Selina Koch (01:16):
Selina Koch, Executive Editor.
Lauren Martz (01:18):
Lauren Martz, Executive Director of
Biopharma Intelligence.
Steve Usdin (01:22):
And Steve Usdin, Washington Editor.
Jeff Cranmer (01:25):
It is back, BioCentury's indispensable,
J.P. Morgan Guide has returned.
Visit jpmguide.com for theinside track on sideline
events, and receptions happeningduring the annual biotech
kickoff in San Francisco.
(01:46):
And hey, if you're hostingsomething special, use the
online form that you'llfind there to make sure you
event appears in our guide.
Again, that's jpmguide.comto make the most of
your JPM 2026 week.
There's a couple of big moverson data today, uh, Structure
(02:06):
Therapeutics, obesity companiesshares doubling in value as
its once daily oral therapyleads to 11% weight loss and
Kymera rises 50% on strongbiomarker results for its
STAT6 degrader for moderateto severe atopic dermatitis.
(02:27):
Both companies gainingbillions in market caps,
Stephen Hansen will haveanalysis of structure's
data on BioCentury.com.
So, hey, let's kick things offwith a month remaining, this
year's already tied for the mostbillion dollar plus M&A deals
of any year in the past 10.
Selina, what's behind the trend?
Selina Koch (02:50):
Yeah, well M&A has certainly been a bright
spot, people keep citing.
So we just do what we do hereand wanted to quantify that.
So by the end of November,so is not yet full year data,
so there could be more, um,there were $37 billion plus
M&A deals announced this yeartime 2025 to 2021 for the
(03:10):
biggest year in the last decade.
And so we broke it down acouple ways, we broke it
down by disease area andwe broke it down by, the
stage of the lead product ofthe company being acquired.
It probably won't surpriseanybody that, you know,
companies with marketedproducts are the biggest set
within that 37.12 but moreinterestingly, maybe there were
(03:32):
six takeouts this year, if abillion dollars or more for
companies in Phase I. That'sup from two last year, one the
year before zero in 2016, 2017.
And even three preclinicalcompanies were taken out
for a high price tag.
And this sort of Lindsay'sanalysis coincided with the
(03:53):
perspective piece written byour colleague, Paul Bonanos, who
had noticed a couple of these,you know, big money takeouts of
early stage companies and hadjust posed the question, you
know, with pharma patent cliffslooming and a limited number
of say mature assets availablefor M&A, you know, are we gonna
start seeing buyers pay more,for early stage companies?
(04:16):
And, you know, Lindsay's datasuggests that maybe that's
already starting to happen.
Simone Fishburn (04:21):
Yeah, I mean, I think it's really
important because a lot of thefocus when people talk about
M&A is on, on consolidationof the big companies.
And you know, we've been talkingfor a couple of years about
looking at this rise of sortof billion dollar plus deals,
where there's a lot of valuein the, you know, let's say $1
(04:42):
to $5 billion range and a lotof companies and assets and you
know, what you're talking about,Selina is also, you know,
regarding the patent cliff.
Well, we know that a lotof the later stage assets
have been picked off, right?
So companies now need togo a little bit earlier
in the value chain.
And, you know, they're stillwilling to put considerable
weight behind some of thosebets that are obviously riskier.
(05:06):
Obviously we've got theJ&J takeout of Halda for
over $3 billion, which is apreclinical company, I think
that raised a lot of eyebrows.
But I think also maybeyou could talk a little
bit about the breakdown oftherapeutic area that Lindsay's
piece sort of laid out.
Selina Koch (05:24):
Yeah.
Um, well, cancer remains King.
Um, if you look at thelast decade's worth of.
These really large M&A deals,it's just a, the slope is just
upward and to the right, with2025 being the decade's highest
number, um, at 20 of them.
For all the hotness thathas been, I&I, the last
(05:45):
three years have been reallysteady for these large
takeouts, at like 7 to 10.
And then the other growtharea, of course, obesity and
cardiovascular seeing sortof year over year increases.
Recently
Simone Fishburn (05:59):
Yeah.
Well, you know, I obviouslyfor companies and in
particular their investors,this is a good exit path
given that the IPO marketis still very constrained.
So I guess we are gonnaimagine the, the beat of $1
billion plus M&A deals isprobably gonna carry on for
a little while into 2026.
Jeff Cranmer (06:20):
All right.
Yeah, and that number as uh,Selina, said earlier, that's $9
billion plus M&A deals year todate, for companies whose lead
programs were in preclinicaltesting or Phase I at the time
the deal was announced andthat to the most in 10 years.
Okay, ASH, uh, unavoidable.
(06:42):
If you have an email inbox,I'm sure a lot of ASH emails
have landed in your lap.
Uh, this week, ASH will delivermore first-in-human in vivo CAR
T data that once again showcasesthe promise of the modality and
justifies the growing pipeline.
There's new data comingfrom Kelonia Therapeutics.
(07:06):
They show that three morepatients have achieved MRD
negativity after treatment withan in vivo CAR T cell therapy.
my colleague Lauren tells methat the questions now include
how long can the near perfecttrack record last, which
technologies will prove safestand most effective, and how
(07:30):
will these results translateto autoimmune diseases.
Let's bring in Lauren,now, uh, Lauren, you gonna
answer all those questions?
Lauren Martz (07:39):
Thanks, Jeff.
I certainly don't have all ofthose answers, but with each
clinical readout, I do thinkwe get a little bit closer.
As you mentioned, at a highlevel, what we've learned from
the latest clinical readoutfor in Vivo CAR T, is that
Kelonia's KLN-1010 a lentiviralvector in vivo CAR T cell
(08:01):
therapy targeting BCMA, isthat it led to MRD negativity
one month after treatment forall three heavily pretreated
multiple myeloma patientsevaluable in that study.
We also know from the abstractthat at least one of the
patients remains MRD negativeat three months, and we should
learn more tomorrow whenthe full data are presented.
(08:23):
I think another important thingabout this readout is that
this was profiled as a latebreaker at ASH, which says a
lot about how much excitementexists around in vivo CAR
T cell therapies right now.
We'll have a story tomorrowonce the full data are reported.
And for that I've been lookinginto the pipeline of in
vivo CAR T cell therapies.
And right now, you know, we wereable to find nearly 40 programs,
(08:48):
and this is what BioCentury'shas been able to identify.
And that I think just reflectsa ton of growth that's happened
over the last few years.
Selina Koch (08:56):
So Lauren, looking across the pipeline,
um, what are the other onesthat have, you know, reported
data and importantly, Iguess, durability data.
Lauren Martz (09:04):
Yeah, Selina, I think durability is, is
the biggest question, andI'm not sure how much data
we have to support that yet.
Um, when AstraZeneca boughtEsoBiotec, we knew that they
had efficacy data from fourpatients, I don't think there's
much information about howdurable the effects are, and
in that case, again, it wasa lentivirus targeting BCMA.
(09:27):
I think that just remainsa big unanswered question,
and that will help.
You know, I think that willhave a big impact on where
this technology ultimatelyends up being used as well.
So durability seems tobe very important when
you're treating cancers.
It may not be as importantfor, um, autoimmune
(09:49):
applications of in vivo Car Ts.
And the autoimmune applicationsare a bit farther behind,
but I think we are startingto see some of the very
early clinical proof ofconcept in those as well.
Jeff Cranmer (10:02):
Okay.
Thank you for that, Lauren.
Uh, looking forward toseeing that one too.
Other readouts, as I mentionedat the top, Praxis, and
Novo's Alzheimer's data forsemaglutide, let's start there.
We discussed the readout onlast week's podcast, data
again at the clinical trialson Alzheimer's Disease Meeting.
(10:25):
Selina, you are eagerto see the full data.
What did you learn?
Selina Koch (10:30):
Yeah, so the days leading up to the US holiday of
Thanksgiving, we just learnedthat Semaglutide did not slow
progression, but we didn't seean y outcomes or the biomarkers?
So this, in terms of a full dataset, I mean, Novo had the data
for like two weeks before theCTAD meeting, so it's top line.
They didn't do a bunch ofsubgroup analyses or anything
like that, but they showedthe, the various clinical
(10:52):
scales, the primary endpoint,CDR sum of boxes is pretty
standard for Alzheimer's.
And then there's a bunchof other standard clinical
functional rating scales.
And probably the most strikingthing is that the curves,
over time of the treatmentgroup and the placebo group
are really just exactlyon top of each other.
There's no argument fora trend toward benefit,
(11:17):
or anything like that.
Really, it was avery clear failure.
And is, Much as we hate tosee failures, um, 'cause
they're not good for patients.
At least the data wereclear in that regard.
The hypothesis though, right,so you always have to ask
yourself, okay, but did the drugdo what it was supposed to do?
And the hypothesis was that,semaglutide was gonna decrease
(11:37):
peripheral inflammation,which was in turn going to
decrease neuroinflammation.
And that was going to bethe mechanism by which it
was gonna help patients.
You have to, you know,measure all of those things
to get a sense of whetheror not it ameliorated
peripheral uh inflammation.
It measured high sensitivityC-reactive protein.
That is what it measured,Novo measured in CLOTS
(11:59):
trials, it's cardiovascularoutcomes trials, for example.
And that was reducedabout 30% as was expected.
Um, but that was the onlyreally, that was the extent
of the characterization ofperipheral inflammation.
Um, and there wasjust a big bucket of
neuroinflammation markers.
And apart from one smallchange on one of them,
they were just not changed.
Steve Usdin (12:21):
So that, that brings up the question that I
had, which is did you have totest a huge number of patients
to learn that it didn't move theneedle on these key biomarkers?
Couldn't they have figurethat out with, I don't know, a
dozen patients or 20 patients.
Selina Koch (12:37):
They absolutely could have done that
work with fewer patients.
Yes.
Simone Fishburn (12:41):
And, and Selina did write that last week.
But I also feel like Selina,they kind of underpowered this.
'Cause when you wrote that pieceof, they could have done it,
you know what Steve is talkingabout, very important, you know,
how you're using your patients.
But you pointed to thefact that they would
learn a lot from this.
And I'm sort of reallywondering how much they did
(13:01):
learn from this because itwas underpowered and maybe
power is the wrong word
Selina Koch (13:05):
Power's the wrong word.
We're only like, we're onlylike 3,800 patients here.
Simone Fishburn (13:10):
Yeah.
So, so power's the wrongword, but it was, it was not
well designed really to getat the peripheral information
because it only had thisone very crude marker of
C-reactive protein, right?
Even though they had multiplemarkers in the brain.
Selina Koch (13:24):
Yeah.
Simone Fishburn (13:24):
Cause it had gotten into the brain, they'd
have been full of data andlike, oh, it, it increases this
marker, but not that marker.
But they didn't reallydo a very rigorous job of
understanding which part ofthe peripheral inflammation
pathways, it, it was activating.
So how do you feel like interms of the design and what
you're able to walk away with?
Selina Koch (13:46):
I feel like the mechanistic piece, even though
there were a lot of biomarkers,was a little underdeveloped.
Yeah, I agree with that.
Like if I thought, okay, there'ssome crosstalk between the
periphery and the central immunesystems, I would wanna know,
what are the candidate pathwaysfor mediating that crosstalk
specifically, and that's notc-reactive protein, right.
(14:08):
That's a general all purposetool, and not thought to act
directly, at that interfaceof the blood-brain barrier.
You might imagine doing asmaller more focused study,
testing those specifichypotheses of how those that
communication might happenacross the blood brain barrier,
which really wasn't done.
(14:28):
Another idea for how theperiphery can influence central
inflammation is by the bloodbrain barrier integrity kind
of breaking down and peripheralimmune cells getting in.
They did have a few, um, two Ithink biomarkers of blood brain
barrier integrity, and thosewere unchanged by semaglutide.
Simone Fishburn (14:46):
So Selina, what I'm kind of hearing is that
this molecule didn't really getinto the brain very well, right?
Selina Koch (14:54):
Yeah, so that's an outstanding question.
The, the, the thought is basedon the, you know, preclinical
data and other data that'savailable that it probably
doesn't get into the brainat any appreciable amount.
Novo did do a small study likein conjunction with the Phase
III trials rather than before.
Um, which was alsopresented at CTAD.
In, in 8 out of 10 peoplethere was a small amount
(15:19):
of semaglutide in thecerebral spinal fluid after
semaglutide treatment um,at, oh, I wanna say maybe
a 10th of a nanogram perliter or something like that.
So far less than you're sayingin the plasma and strangely
did not seem to correlatewith the level in the plasma.
So in Peter Johannsen whotalked about that said very
(15:40):
specifically, look, even ifsmall amounts get into the
CSF, it's a very differentquestion whether or not
any of that penetratesinto the brain parenchyma
in any appreciable amount.
Simone Fishburn (15:48):
Okay, so let me go back to Steve's
question now, or Steve'spoint, which is you do this
trial on 3000 plus patients.
You don't think you might do alittle bit more work on whether
the molecule gets in the brain.
Selina Koch (16:02):
I know, I know there, there are things
that could have been donebefore jumping into a nearly
4,000 patient Phase IIItrial, especially given
the precious resource thatpatients are for trials.
Jeff Cranmer (16:15):
Let's jump to some good news.
shares of Praxis PrecisionMedicines rose 31% on Friday
after a Phase II/III study ofthe company's sodium channel
modulator for a couple ofsubtypes of developmental and
epileptic encephalopathy, wasstopped early for efficacy.
(16:37):
Stock is still moving up today.
These came out of theAmerican Epilepsy Society
Annual Meeting, uh, thefull data came out Saturday.
Uh, Lauren, there'sa small molecule, why
is that significant?
I know, the seizures thatthey were evaluating are
associated with a high riskof autism spectrum disorders.
(17:00):
Um, what did you learnin writing this story?
Lauren Martz (17:03):
I think the fact that this is a small
molecule is one of the thingsthat makes this data so,
exciting for Praxis, and,and just for the field.
This developmental and epilepticencephalopathy, is specifically
genetic form caused by mutationsin SCN2A and SCN8 A and here
(17:24):
we have a small molecule thatcan treat specifically the
genetic form of this disease.
You know, it's been aparticularly difficult year
to advance cell and genetherapies through the clinic.
When you look at the pipelinefor these types of DEEs, a lot
of the development is focusedin cell and gene therapies, uh,
(17:45):
gene therapies in particular.
And so just given thecommercial hurdles and
some of the safety issues.
I think it's just a goodreminder that with the advances
that we're seeing in smallmolecule drug development,
there is an opportunityin some cases, to design
drugs that can treat thesekinds of genetic disorders.
And then the other thing thatI think is really interesting
here is that there's an autism,a genetic autism component
(18:09):
involved here as well.
So this is, you know, a trialthat's focused on epilepsy
associated with these mutations.
But SCN2A, for example,is also one of the most
well characterized geneticrisk factors for autism.
I think progress in helpingrestore function of the
sodium channel couldhave an impact on autism.
(18:32):
And, and this is definitely ahot area for drug development
for different reasons right now.
Selina Koch (18:37):
Yeah, probably worth pointing out, in this
era of really tough funding forgene therapies, it's the safety
issues we've seen this year, thecontinued commercial challenges.
That modality piece is probablyreally important, and it's
not the first, you know, wesaw Roche kind of prove this.
That a small molecule cancome into a space where
(19:00):
there's antisense and genetherapy and, and kind of
outcompete, that was Evrysdiin spinal muscular atrophy.
Simone Fishburn (19:09):
Yeah, but I, I think that's, you know,
both of these things aresort of converging on real
actual steps within autism.
Obviously there's a lotof noise political, that
part of the program we'llget to after the break, I
guess, Jeff, in terms of thepolitics around these things.
But this is obviously aboutepilepsy, which is a feature of
(19:30):
some autism spectrum disorders.
But I think that there's abelief that there may also
be benefits for some of thecognitive let's say features
or other features of autism.
And I think really what I'mtrying to say is this is
generally good news, notonly for the epilepsy part
of it, but also for the ideathat with genetics and with
(19:52):
these various approaches,there is progress being made
maybe slowly, but progressbeing made within autism.
Is that how you look at it?
Lauren Martz (20:00):
Yeah, Simone, that is how I see it.
And I think it's also importantto note that this EMBOLD
Study, that was stopped early,specifically looked at seizure
reduction endpoints in theclinic for clinical efficacy.
But Praxis PrecisionMedicines is also running a
second registrational study.
(20:20):
That is looking at DEEsunrestricted, um, you
know, not limited to thethese specific mutations.
And in that study they arelooking at different efficacy
endpoints more broadly.
Some of those are relatedto symptoms that may be more
relevant to other aspects ofautism spectrum disorders.
Selina Koch (20:41):
I think that's gonna be key.
And the other thing is ifyou treat very, very early,
right, so these carry withthem these genetic defects,
a risk of developing autism.
So I wonder if we wouldsee, you know, in the
real world data some day,a decrease in that risk.
Jeff Cranmer (20:58):
All right, we're gonna cut to a quick
break, all of those storiesyou'll find on BioCentury.com,
BioCenturypodcast.com.
If you like what you'rehearing like, and subscribe
to BioCentury This Week.
We'll be back to talk about awild week in Washington with our
Washington Editor, Steve Usdin.
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Jeff Cranmer (22:07):
We are back on the BioCentury This Week podcast.
Let's get to Washington.
Steve, I think.
You had a personal best in thenumber of reports that you filed
last week and where to begin?
Steve Usdin (22:24):
Well, I think that when we left, listeners
to the podcast last week, uh,Richard Pazdur was still the the
Director of the Center for DrugEvaluation and Research at FDA.
There was, uh, some level ofconcern around a memo that
Vinay Prasad, the Director ofCBER, had written about, vaccine
(22:46):
policy and, and a new frameworkfor vaccine regulation.
And things have, look, we'vehad another, another turn on
the, on the rollercoaster.
And this one is, uh, youknow, kind of a barrel roll.
So first, Richard Pazdurannounced his retirement
starting at the end of December,so he was on the job less than
three weeks, and then he left.
(23:08):
Almost every living FormerFDA commissioner signed
onto a commentary that waspublished in the New England
Journal of Medicine warningthat FDA's new vaccine
policies constitute a publichealth crisis and expressing
broader concerns aboutCommissioner Marty Makary's
management of the Agency.
And then Tracy Beth Høeg wasnamed Acting CDER Director to
(23:31):
replace, um, Richard Pazdur,who for the next few weeks, has
gone back to being head of theOncology Center of Excellence.
So you could hear the gaspsfrom life sciences executives
around the country and aroundthe world when they heard
that Richard Pazdur wasretiring as CDER director.
(23:53):
And then you could hear thephones hitting the floor
when they started gettingthe texts announcing that
Tracy Beth Høeg had beennamed Acting CDER Director.
So the short form she's viewedinside FDA and among regulated
industry, as unqualified forthe job and an ideologue.
She's likely to provokea wave of resignations at
(24:15):
FDA, that's what I'm hearingfrom people in the Agency.
And I think, greateruncertainty for drug developers.
Her appointment and Pazdursdeparture or as imminent
departure, I think aresigns that drug reviews
are going to be influencedby political pressures and
ideological influences.
Simone Fishburn (24:33):
Just a minute before we get to Dr.
Høeg as the head of CDER.
Steve, you know, we've beenrunning a survey, which is now
closed and we'll be getting thatout this week from the survey
responses, here's a heads upto everybody from the survey
responses as well as from a lotof personal interactions and
conversations that we had atvarious meetings last week with
(24:56):
biopharma VCs, biotech heads.
There was really a feelingthat Pazdur's appointment
was the biggest stabilizingforce for FDA, you know,
he was the grownup inthe room kind of thing.
Most of all I thinkis the stability.
Now, his departure has certainlygot a lot of people very
worried about next year, evenbefore they knew who the next
(25:20):
CDER Director would be, right.
What is there in terms of, haveyou got any good news, Steve,
upside calming things thatyou can tell people out there?
Steve Usdin (25:30):
From FDA, there's no good news.
I think there's, there's newsthat people interpret as the
possibility of good news, right.
So, you know, we'vetalked about it on the,
on the podcast before.
There's, this PlausibleMechanism Pathway, which,
leaving aside the name of it,has the potential to unlock
the development of therapiesfor very rare conditions
(25:53):
and bespoke therapiesfor very rare conditions.
But it is far from certain thatit's gonna be implemented in
a way that actually does that.
But if you're lookingfor good news, you know,
there's a potential there.
There's also, something elsethat happened last week, which
was that one, one of the thingsthat's been in the works at
FDA for some time is an ideathat Commissioner Marty Makary
(26:15):
and CBER Director Vinay Prasadhave of putting out a statement
saying that the defaultassumption at FDA going forward
will be that companies will haveto perform a single clinical
trial, single pivotal clinicaltrial to support drug approval.
They had been trying to get astatement saying that through
(26:36):
HHS Legal Office for sometime, and hadn't been able
to get final sign off on it.
Commissioner Makary discussedit, basically leaked the
memo, um, to a reporter fromanother publication last week.
So it's been in the newsquite a bit, but the, the
press release still hasn'tbeen released, so we don't
know exactly what's in it.
And what's more, wedon't know how FDA might
(26:58):
put it into practice.
So you could look atthat as good, you could
look at it as bad.
It's certainly going to createa great deal of uncertainty.
You know, translating a, a pressrelease into predictable policy
is going to be challenging.
Simone Fishburn (27:14):
So what are your expectations?
What do we need toknow about Dr. Høeg
Steve Usdin (27:20):
So she is an MD, specializing in sports medicine,
she has a PhD in epidemiology.
She is never runa clinical trial.
She's never reviewed a drug.
She has no regulatoryexperience whatsoever.
She rose to prominenceas a COVID contrarian,
during the pandemic.
She advised Florida SurgeonGeneral Joseph Ladapo on
(27:40):
anti-vaccine policies thathave been heavily criticized
by public health experts.
She's played a leading roleas FDA's representative
to the ACIP that's theCDC's Advisory Committee
on immunization practices.
And which, in her capacitythere, she's challenged
the need for mandatoryvaccination of children.
(28:01):
She's called for changes tothe vaccine schedule that will
result in American childrenreceiving fewer vaccines.
As a Senior Advisor to FDACommissioner Makary, Høeg's
been closely involved withthe Commissioner National
Priority Voucher Program.
She's close to CBER Director,Vinay Prasad, and helped
write a memo, the one thatI mentioned earlier, uh,
(28:22):
announcing new vaccine policies.
Last week, every living FDACommissioner except one Stephen
Hahn, signed a commentarythat was published by the New
England Journal of Medicinethat condemned that memo
saying it will have disastrousconsequences for vaccine
development, and public health.
People I know who haveinteracted with Høeg at FDA,
say she's scientificallycurious um, in meetings she
(28:44):
asks probing questions or wantsto get into the details, but
they also say that she's anadvocate, not a regulator, that
she starts with conclusionsand cherry picks data to
get to the desired response.
Uh, and the FDA staff I'vespoken with say Høeg has
used that, that approach,and she's used observational
data in ways that aren'tscientifically appropriate.
To make assertionsabout drug safety.
(29:06):
One example, she was incharge of a review of
COVID vaccines that ledto restrictions that were
posed by longtime scientistsand civil servants at FDA.
Phil Krause, the Former DeputyHead of Vaccines at FDA, and
Luciana Borio, the FormerActing FDA Chief Scientist,
wrote a commentary that wepublished in BioCentury,
about the actions that Høegtook on COVID vaccines.
(29:28):
And they wrote that shiftingstandards and late stage
demands for new data based onfaulty scientific assumptions
have eroded trust, delayedaccess to important tools,
and discourage developers fromadvancing vaccine innovation.
I think we can expect thatHøeg's gonna move on MAHA
priorities, restricting accessto, SSRIs and other psychiatric
(29:50):
drugs for adolescents.
Taking action to reduce accessto puberty blockers, supporting
access to psychedelics.
And, and other, other steps Ithink that are, you know, on
the MAHA agenda, that's what wecan expect that she's gonna do.
Jeff Cranmer (30:04):
Steve, I'm just curious, has Bill Cassidy
made any comments aboutwhat's been happening at FDA?
Steve Usdin (30:11):
So you're, you're referring to Senator Cassidy,
who's the Chairman of theSenate Health Education Labor
Committee, he has made, publicstatements about the ACIP.
He's really kind of apoplectic,about what ACIP has done, in
terms of reducing access ofnewborns or recommendations
for newborns to get accessto hepatitis B vaccines.
(30:35):
It's a field that, Cassidyknows well, he's a physician,
and he treated a lotof hepatitis B patients.
And he's extremely concernedabout what ACIP has done.
I haven't heard him sayanything publicly about FDA.
Simone Fishburn (30:51):
Steve.
Well, I think, you know, wewould agree more with the
orthodoxy on vaccines thanlet's say on the MAHA agenda.
And I understand that Dr.
Høeg has sort of had a lot tosay about the COVID vaccines.
Also acknowledging thatthere are many people with
different views about that.
How relevant do you thinkher COVID vaccine position
(31:11):
is gonna be in her roleas the Head of CDER?
Is there daylight between those?
Steve Usdin (31:17):
Well, she doesn't regulate vaccines at CDER,
CDER doesn't regulate vaccines.
But I think that what itshows is how she thinks
about things, and the factthat, she's willing, and
eager really to take actionsand to take regulatory
actions based on ideologicalprinciples rather than, the,
(31:40):
uh, scientific consensus.
She's also acting, and thisis consistent with what
Marty Makary has been doingas FDA Commissioner, in the
absence of public advisorycommittees or other forms
that would create transparencyand accountability around
FDA's actions on topics thataffect public health and the
health of individual patients.
(32:02):
Not to mention the ability ofcompanies to develop drugs.
Jeff Cranmer (32:06):
Steve, a few other things are on
the agenda in Washington.
I don't know how much isgonna get done, we've been
talking a lot about thecomeback of the Biosecure Act.
Um, where does that stand?
Steve Usdin (32:18):
So, uh, the Biosecure Act, has been
included in the House versionof the National Defense
Authorization Act, the NDAA,which is a must pass bill.
It's a bill that's gonnabe passed very soon.
It's almost certain thatBiosecure 2.0 will be
included in the bill.
People may remember,we've talked about
(32:38):
this on the podcast.
The new version of Biosecurediffers from the version that
was pending last year becauserather than listing specific
companies, it creates a processfor the Administration right
now, the Trump Administrationto determine whether companies
are so-called biotechnologycompanies of concern.
(33:00):
And for those companies therewill be restrictions on US
companies or companies thatwanna sell their products in the
U.S. Accessing their services.
There's a five-yeargrandfathering period and
there's also limits on theeffectiveness of the, of
the sanctions, the effectof the sanctions on the
ability of companies to selldrugs in the United States.
(33:21):
A lot is gonna depend onhow the law is interpreted
or implemented by the,the Trump Administration.
Another bill that's almostcertain to be included in the
NDAA is something called theFight China Act, which imposes
sanctions on certain Chineseentities and restricts or
requires notification of USinvestments in specified high
(33:44):
risk technologies in China.
Basically it establishesan outbound investment
screening regime.
It isn't directly targeted atbiotech, and in fact, there
are provisions in it that, thatkind of provide a carve out
for certain research activitiesthat are conducted in China,
but nonetheless, it's likelyto impact of biotech companies.
(34:05):
Again, a lot of it's gonnadepend on how the Trump
Administration interprets it,but some kinds of collaboration,
some kinds of investments, incompanies in China that, use,
uh, advanced chipsets, forexample, that are developed
in China or use advancedAI systems that are Chinese
systems, could be, subject tonotification requirements or
(34:27):
even have to disinvest in inprojects in China, depending
on how the act is interpretedby the Administration.
Jeff Cranmer (34:35):
Okay, uh, you can read all of Steve's
stories, BioCenturypodcast.com.
We will be back next week.
Don't forget to subscribeto BioCentury This Week.
And check out the latestfrom our sister podcast
The BioCentury Show.
Selina sat down withBill Hinshaw to talk
(34:56):
precision medicine.
Bill is CEO of ForeBiotherapeutics.
Kendall Square Orchestraprovides the music for
BioCentury 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.
[AI-generated transcript.]
Jeff Cranmer (00:01):
Fueled by cancer, obesity, and cardiovascular
deals billion dollar plustakeouts in biotech are
on the rise, we'll take acloser look on the latest
BioCentury's This Week podcast.
Plus, welcome to ASH Monday,data have been pouring out of
(00:21):
Orlando from the HematologySociety's Annual Meeting, we'll
zero in on first-in-human invivo CAR T data from Kelonia.
And more data, anotherPraxis win provides
much needed progress inrare genetic epilepsies.
And Selina got that datashe was looking for the full
(00:44):
data set for semaglutide,uh, presented at CTAD,
semaglutide was supposedto quench CNS inflammation,
it didn't, Selina will diginto the details for you.
And another tumultuousweek at FDA, Steve will
give his analysis on theback half of the podcast.
(01:06):
I'm Jeff Cranmer, one ofthe executive editors here
at BioCentury, and joiningme today are my colleagues.
Simone Fishburn (01:13):
Simon Fishburn, Editor in Chief.
Selina Koch (01:16):
Selina Koch, Executive Editor.
Lauren Martz (01:18):
Lauren Martz, Executive Director of
Biopharma Intelligence.
Steve Usdin (01:22):
And Steve Usdin, Washington Editor.
Jeff Cranmer (01:25):
It is back, BioCentury's indispensable,
J.P. Morgan Guide has returned.
Visit jpmguide.com for theinside track on sideline
events, and receptions happeningduring the annual biotech
kickoff in San Francisco.
(01:46):
And hey, if you're hostingsomething special, use the
online form that you'llfind there to make sure you
event appears in our guide.
Again, that's jpmguide.comto make the most of
your JPM 2026 week.
There's a couple of big moverson data today, uh, Structure
(02:06):
Therapeutics, obesity companiesshares doubling in value as
its once daily oral therapyleads to 11% weight loss and
Kymera rises 50% on strongbiomarker results for its
STAT6 degrader for moderateto severe atopic dermatitis.
(02:27):
Both companies gainingbillions in market caps,
Stephen Hansen will haveanalysis of structure's
data on BioCentury.com.
So, hey, let's kick things offwith a month remaining, this
year's already tied for the mostbillion dollar plus M&A deals
of any year in the past 10.
Selina, what's behind the trend?
Selina Koch (02:50):
Yeah, well M&A has certainly been a bright
spot, people keep citing.
So we just do what we do hereand wanted to quantify that.
So by the end of November,so is not yet full year data,
so there could be more, um,there were $37 billion plus
M&A deals announced this yeartime 2025 to 2021 for the
(03:10):
biggest year in the last decade.
And so we broke it down acouple ways, we broke it
down by disease area andwe broke it down by, the
stage of the lead product ofthe company being acquired.
It probably won't surpriseanybody that, you know,
companies with marketedproducts are the biggest set
within that 37.12 but moreinterestingly, maybe there were
(03:32):
six takeouts this year, if abillion dollars or more for
companies in Phase I. That'sup from two last year, one the
year before zero in 2016, 2017.
And even three preclinicalcompanies were taken out
for a high price tag.
And this sort of Lindsay'sanalysis coincided with the
(03:53):
perspective piece written byour colleague, Paul Bonanos, who
had noticed a couple of these,you know, big money takeouts of
early stage companies and hadjust posed the question, you
know, with pharma patent cliffslooming and a limited number
of say mature assets availablefor M&A, you know, are we gonna
start seeing buyers pay more,for early stage companies?
(04:16):
And, you know, Lindsay's datasuggests that maybe that's
already starting to happen.
Simone Fishburn (04:21):
Yeah, I mean, I think it's really
important because a lot of thefocus when people talk about
M&A is on, on consolidationof the big companies.
And you know, we've been talkingfor a couple of years about
looking at this rise of sortof billion dollar plus deals,
where there's a lot of valuein the, you know, let's say $1
(04:42):
to $5 billion range and a lotof companies and assets and you
know, what you're talking about,Selina is also, you know,
regarding the patent cliff.
Well, we know that a lotof the later stage assets
have been picked off, right?
So companies now need togo a little bit earlier
in the value chain.
And, you know, they're stillwilling to put considerable
weight behind some of thosebets that are obviously riskier.
(05:06):
Obviously we've got theJ&J takeout of Halda for
over $3 billion, which is apreclinical company, I think
that raised a lot of eyebrows.
But I think also maybeyou could talk a little
bit about the breakdown oftherapeutic area that Lindsay's
piece sort of laid out.
Selina Koch (05:24):
Yeah.
Um, well, cancer remains King.
Um, if you look at thelast decade's worth of.
These really large M&A deals,it's just a, the slope is just
upward and to the right, with2025 being the decade's highest
number, um, at 20 of them.
For all the hotness thathas been, I&I, the last
(05:45):
three years have been reallysteady for these large
takeouts, at like 7 to 10.
And then the other growtharea, of course, obesity and
cardiovascular seeing sortof year over year increases.
Recently
Simone Fishburn (05:59):
Yeah.
Well, you know, I obviouslyfor companies and in
particular their investors,this is a good exit path
given that the IPO marketis still very constrained.
So I guess we are gonnaimagine the, the beat of $1
billion plus M&A deals isprobably gonna carry on for
a little while into 2026.
Jeff Cranmer (06:20):
All right.
Yeah, and that number as uh,Selina, said earlier, that's $9
billion plus M&A deals year todate, for companies whose lead
programs were in preclinicaltesting or Phase I at the time
the deal was announced andthat to the most in 10 years.
Okay, ASH, uh, unavoidable.
(06:42):
If you have an email inbox,I'm sure a lot of ASH emails
have landed in your lap.
Uh, this week, ASH will delivermore first-in-human in vivo CAR
T data that once again showcasesthe promise of the modality and
justifies the growing pipeline.
There's new data comingfrom Kelonia Therapeutics.
(07:06):
They show that three morepatients have achieved MRD
negativity after treatment withan in vivo CAR T cell therapy.
my colleague Lauren tells methat the questions now include
how long can the near perfecttrack record last, which
technologies will prove safestand most effective, and how
(07:30):
will these results translateto autoimmune diseases.
Let's bring in Lauren,now, uh, Lauren, you gonna
answer all those questions?
Lauren Martz (07:39):
Thanks, Jeff.
I certainly don't have all ofthose answers, but with each
clinical readout, I do thinkwe get a little bit closer.
As you mentioned, at a highlevel, what we've learned from
the latest clinical readoutfor in Vivo CAR T, is that
Kelonia's KLN-1010 a lentiviralvector in vivo CAR T cell
(08:01):
therapy targeting BCMA, isthat it led to MRD negativity
one month after treatment forall three heavily pretreated
multiple myeloma patientsevaluable in that study.
We also know from the abstractthat at least one of the
patients remains MRD negativeat three months, and we should
learn more tomorrow whenthe full data are presented.
(08:23):
I think another important thingabout this readout is that
this was profiled as a latebreaker at ASH, which says a
lot about how much excitementexists around in vivo CAR
T cell therapies right now.
We'll have a story tomorrowonce the full data are reported.
And for that I've been lookinginto the pipeline of in
vivo CAR T cell therapies.
And right now, you know, we wereable to find nearly 40 programs,
(08:48):
and this is what BioCentury'shas been able to identify.
And that I think just reflectsa ton of growth that's happened
over the last few years.
Selina Koch (08:56):
So Lauren, looking across the pipeline,
um, what are the other onesthat have, you know, reported
data and importantly, Iguess, durability data.
Lauren Martz (09:04):
Yeah, Selina, I think durability is, is
the biggest question, andI'm not sure how much data
we have to support that yet.
Um, when AstraZeneca boughtEsoBiotec, we knew that they
had efficacy data from fourpatients, I don't think there's
much information about howdurable the effects are, and
in that case, again, it wasa lentivirus targeting BCMA.
(09:27):
I think that just remainsa big unanswered question,
and that will help.
You know, I think that willhave a big impact on where
this technology ultimatelyends up being used as well.
So durability seems tobe very important when
you're treating cancers.
It may not be as importantfor, um, autoimmune
(09:49):
applications of in vivo Car Ts.
And the autoimmune applicationsare a bit farther behind,
but I think we are startingto see some of the very
early clinical proof ofconcept in those as well.
Jeff Cranmer (10:02):
Okay.
Thank you for that, Lauren.
Uh, looking forward toseeing that one too.
Other readouts, as I mentionedat the top, Praxis, and
Novo's Alzheimer's data forsemaglutide, let's start there.
We discussed the readout onlast week's podcast, data
again at the clinical trialson Alzheimer's Disease Meeting.
(10:25):
Selina, you are eagerto see the full data.
What did you learn?
Selina Koch (10:30):
Yeah, so the days leading up to the US holiday of
Thanksgiving, we just learnedthat Semaglutide did not slow
progression, but we didn't seean y outcomes or the biomarkers?
So this, in terms of a full dataset, I mean, Novo had the data
for like two weeks before theCTAD meeting, so it's top line.
They didn't do a bunch ofsubgroup analyses or anything
like that, but they showedthe, the various clinical
(10:52):
scales, the primary endpoint,CDR sum of boxes is pretty
standard for Alzheimer's.
And then there's a bunchof other standard clinical
functional rating scales.
And probably the most strikingthing is that the curves,
over time of the treatmentgroup and the placebo group
are really just exactlyon top of each other.
There's no argument fora trend toward benefit,
(11:17):
or anything like that.
Really, it was avery clear failure.
And is, Much as we hate tosee failures, um, 'cause
they're not good for patients.
At least the data wereclear in that regard.
The hypothesis though, right,so you always have to ask
yourself, okay, but did the drugdo what it was supposed to do?
And the hypothesis was that,semaglutide was gonna decrease
(11:37):
peripheral inflammation,which was in turn going to
decrease neuroinflammation.
And that was going to bethe mechanism by which it
was gonna help patients.
You have to, you know,measure all of those things
to get a sense of whetheror not it ameliorated
peripheral uh inflammation.
It measured high sensitivityC-reactive protein.
That is what it measured,Novo measured in CLOTS
(11:59):
trials, it's cardiovascularoutcomes trials, for example.
And that was reducedabout 30% as was expected.
Um, but that was the onlyreally, that was the extent
of the characterization ofperipheral inflammation.
Um, and there wasjust a big bucket of
neuroinflammation markers.
And apart from one smallchange on one of them,
they were just not changed.
Steve Usdin (12:21):
So that, that brings up the question that I
had, which is did you have totest a huge number of patients
to learn that it didn't move theneedle on these key biomarkers?
Couldn't they have figurethat out with, I don't know, a
dozen patients or 20 patients.
Selina Koch (12:37):
They absolutely could have done that
work with fewer patients.
Yes.
Simone Fishburn (12:41):
And, and Selina did write that last week.
But I also feel like Selina,they kind of underpowered this.
'Cause when you wrote that pieceof, they could have done it,
you know what Steve is talkingabout, very important, you know,
how you're using your patients.
But you pointed to thefact that they would
learn a lot from this.
And I'm sort of reallywondering how much they did
(13:01):
learn from this because itwas underpowered and maybe
power is the wrong word
Selina Koch (13:05):
Power's the wrong word.
We're only like, we're onlylike 3,800 patients here.
Simone Fishburn (13:10):
Yeah.
So, so power's the wrongword, but it was, it was not
well designed really to getat the peripheral information
because it only had thisone very crude marker of
C-reactive protein, right?
Even though they had multiplemarkers in the brain.
Selina Koch (13:24):
Yeah.
Simone Fishburn (13:24):
Cause it had gotten into the brain, they'd
have been full of data andlike, oh, it, it increases this
marker, but not that marker.
But they didn't reallydo a very rigorous job of
understanding which part ofthe peripheral inflammation
pathways, it, it was activating.
So how do you feel like interms of the design and what
you're able to walk away with?
Selina Koch (13:46):
I feel like the mechanistic piece, even though
there were a lot of biomarkers,was a little underdeveloped.
Yeah, I agree with that.
Like if I thought, okay, there'ssome crosstalk between the
periphery and the central immunesystems, I would wanna know,
what are the candidate pathwaysfor mediating that crosstalk
specifically, and that's notc-reactive protein, right.
(14:08):
That's a general all purposetool, and not thought to act
directly, at that interfaceof the blood-brain barrier.
You might imagine doing asmaller more focused study,
testing those specifichypotheses of how those that
communication might happenacross the blood brain barrier,
which really wasn't done.
(14:28):
Another idea for how theperiphery can influence central
inflammation is by the bloodbrain barrier integrity kind
of breaking down and peripheralimmune cells getting in.
They did have a few, um, two Ithink biomarkers of blood brain
barrier integrity, and thosewere unchanged by semaglutide.
Simone Fishburn (14:46):
So Selina, what I'm kind of hearing is that
this molecule didn't really getinto the brain very well, right?
Selina Koch (14:54):
Yeah, so that's an outstanding question.
The, the, the thought is basedon the, you know, preclinical
data and other data that'savailable that it probably
doesn't get into the brainat any appreciable amount.
Novo did do a small study likein conjunction with the Phase
III trials rather than before.
Um, which was alsopresented at CTAD.
In, in 8 out of 10 peoplethere was a small amount
(15:19):
of semaglutide in thecerebral spinal fluid after
semaglutide treatment um,at, oh, I wanna say maybe
a 10th of a nanogram perliter or something like that.
So far less than you're sayingin the plasma and strangely
did not seem to correlatewith the level in the plasma.
So in Peter Johannsen whotalked about that said very
(15:40):
specifically, look, even ifsmall amounts get into the
CSF, it's a very differentquestion whether or not
any of that penetratesinto the brain parenchyma
in any appreciable amount.
Simone Fishburn (15:48):
Okay, so let me go back to Steve's
question now, or Steve'spoint, which is you do this
trial on 3000 plus patients.
You don't think you might do alittle bit more work on whether
the molecule gets in the brain.
Selina Koch (16:02):
I know, I know there, there are things
that could have been donebefore jumping into a nearly
4,000 patient Phase IIItrial, especially given
the precious resource thatpatients are for trials.
Jeff Cranmer (16:15):
Let's jump to some good news.
shares of Praxis PrecisionMedicines rose 31% on Friday
after a Phase II/III study ofthe company's sodium channel
modulator for a couple ofsubtypes of developmental and
epileptic encephalopathy, wasstopped early for efficacy.
(16:37):
Stock is still moving up today.
These came out of theAmerican Epilepsy Society
Annual Meeting, uh, thefull data came out Saturday.
Uh, Lauren, there'sa small molecule, why
is that significant?
I know, the seizures thatthey were evaluating are
associated with a high riskof autism spectrum disorders.
(17:00):
Um, what did you learnin writing this story?
Lauren Martz (17:03):
I think the fact that this is a small
molecule is one of the thingsthat makes this data so,
exciting for Praxis, and,and just for the field.
This developmental and epilepticencephalopathy, is specifically
genetic form caused by mutationsin SCN2A and SCN8 A and here
(17:24):
we have a small molecule thatcan treat specifically the
genetic form of this disease.
You know, it's been aparticularly difficult year
to advance cell and genetherapies through the clinic.
When you look at the pipelinefor these types of DEEs, a lot
of the development is focusedin cell and gene therapies, uh,
(17:45):
gene therapies in particular.
And so just given thecommercial hurdles and
some of the safety issues.
I think it's just a goodreminder that with the advances
that we're seeing in smallmolecule drug development,
there is an opportunityin some cases, to design
drugs that can treat thesekinds of genetic disorders.
And then the other thing thatI think is really interesting
here is that there's an autism,a genetic autism component
(18:09):
involved here as well.
So this is, you know, a trialthat's focused on epilepsy
associated with these mutations.
But SCN2A, for example,is also one of the most
well characterized geneticrisk factors for autism.
I think progress in helpingrestore function of the
sodium channel couldhave an impact on autism.
(18:32):
And, and this is definitely ahot area for drug development
for different reasons right now.
Selina Koch (18:37):
Yeah, probably worth pointing out, in this
era of really tough funding forgene therapies, it's the safety
issues we've seen this year, thecontinued commercial challenges.
That modality piece is probablyreally important, and it's
not the first, you know, wesaw Roche kind of prove this.
That a small molecule cancome into a space where
(19:00):
there's antisense and genetherapy and, and kind of
outcompete, that was Evrysdiin spinal muscular atrophy.
Simone Fishburn (19:09):
Yeah, but I, I think that's, you know,
both of these things aresort of converging on real
actual steps within autism.
Obviously there's a lotof noise political, that
part of the program we'llget to after the break, I
guess, Jeff, in terms of thepolitics around these things.
But this is obviously aboutepilepsy, which is a feature of
(19:30):
some autism spectrum disorders.
But I think that there's abelief that there may also
be benefits for some of thecognitive let's say features
or other features of autism.
And I think really what I'mtrying to say is this is
generally good news, notonly for the epilepsy part
of it, but also for the ideathat with genetics and with
(19:52):
these various approaches,there is progress being made
maybe slowly, but progressbeing made within autism.
Is that how you look at it?
Lauren Martz (20:00):
Yeah, Simone, that is how I see it.
And I think it's also importantto note that this EMBOLD
Study, that was stopped early,specifically looked at seizure
reduction endpoints in theclinic for clinical efficacy.
But Praxis PrecisionMedicines is also running a
second registrational study.
(20:20):
That is looking at DEEsunrestricted, um, you
know, not limited to thethese specific mutations.
And in that study they arelooking at different efficacy
endpoints more broadly.
Some of those are relatedto symptoms that may be more
relevant to other aspects ofautism spectrum disorders.
Selina Koch (20:41):
I think that's gonna be key.
And the other thing is ifyou treat very, very early,
right, so these carry withthem these genetic defects,
a risk of developing autism.
So I wonder if we wouldsee, you know, in the
real world data some day,a decrease in that risk.
Jeff Cranmer (20:58):
All right, we're gonna cut to a quick
break, all of those storiesyou'll find on BioCentury.com,
BioCenturypodcast.com.
If you like what you'rehearing like, and subscribe
to BioCentury This Week.
We'll be back to talk about awild week in Washington with our
Washington Editor, Steve Usdin.
Alanna Farro (21:20):
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Jeff Cranmer (22:07):
We are back on the BioCentury This Week podcast.
Let's get to Washington.
Steve, I think.
You had a personal best in thenumber of reports that you filed
last week and where to begin?
Steve Usdin (22:24):
Well, I think that when we left, listeners
to the podcast last week, uh,Richard Pazdur was still the the
Director of the Center for DrugEvaluation and Research at FDA.
There was, uh, some level ofconcern around a memo that
Vinay Prasad, the Director ofCBER, had written about, vaccine
(22:46):
policy and, and a new frameworkfor vaccine regulation.
And things have, look, we'vehad another, another turn on
the, on the rollercoaster.
And this one is, uh, youknow, kind of a barrel roll.
So first, Richard Pazdurannounced his retirement
starting at the end of December,so he was on the job less than
three weeks, and then he left.
(23:08):
Almost every living FormerFDA commissioner signed
onto a commentary that waspublished in the New England
Journal of Medicine warningthat FDA's new vaccine
policies constitute a publichealth crisis and expressing
broader concerns aboutCommissioner Marty Makary's
management of the Agency.
And then Tracy Beth Høeg wasnamed Acting CDER Director to
(23:31):
replace, um, Richard Pazdur,who for the next few weeks, has
gone back to being head of theOncology Center of Excellence.
So you could hear the gaspsfrom life sciences executives
around the country and aroundthe world when they heard
that Richard Pazdur wasretiring as CDER director.
(23:53):
And then you could hear thephones hitting the floor
when they started gettingthe texts announcing that
Tracy Beth Høeg had beennamed Acting CDER Director.
So the short form she's viewedinside FDA and among regulated
industry, as unqualified forthe job and an ideologue.
She's likely to provokea wave of resignations at
(24:15):
FDA, that's what I'm hearingfrom people in the Agency.
And I think, greateruncertainty for drug developers.
Her appointment and Pazdursdeparture or as imminent
departure, I think aresigns that drug reviews
are going to be influencedby political pressures and
ideological influences.
Simone Fishburn (24:33):
Just a minute before we get to Dr.
Høeg as the head of CDER.
Steve, you know, we've beenrunning a survey, which is now
closed and we'll be getting thatout this week from the survey
responses, here's a heads upto everybody from the survey
responses as well as from a lotof personal interactions and
conversations that we had atvarious meetings last week with
(24:56):
biopharma VCs, biotech heads.
There was really a feelingthat Pazdur's appointment
was the biggest stabilizingforce for FDA, you know,
he was the grownup inthe room kind of thing.
Most of all I thinkis the stability.
Now, his departure has certainlygot a lot of people very
worried about next year, evenbefore they knew who the next
(25:20):
CDER Director would be, right.
What is there in terms of, haveyou got any good news, Steve,
upside calming things thatyou can tell people out there?
Steve Usdin (25:30):
From FDA, there's no good news.
I think there's, there's newsthat people interpret as the
possibility of good news, right.
So, you know, we'vetalked about it on the,
on the podcast before.
There's, this PlausibleMechanism Pathway, which,
leaving aside the name of it,has the potential to unlock
the development of therapiesfor very rare conditions
(25:53):
and bespoke therapiesfor very rare conditions.
But it is far from certain thatit's gonna be implemented in
a way that actually does that.
But if you're lookingfor good news, you know,
there's a potential there.
There's also, something elsethat happened last week, which
was that one, one of the thingsthat's been in the works at
FDA for some time is an ideathat Commissioner Marty Makary
(26:15):
and CBER Director Vinay Prasadhave of putting out a statement
saying that the defaultassumption at FDA going forward
will be that companies will haveto perform a single clinical
trial, single pivotal clinicaltrial to support drug approval.
They had been trying to get astatement saying that through
(26:36):
HHS Legal Office for sometime, and hadn't been able
to get final sign off on it.
Commissioner Makary discussedit, basically leaked the
memo, um, to a reporter fromanother publication last week.
So it's been in the newsquite a bit, but the, the
press release still hasn'tbeen released, so we don't
know exactly what's in it.
And what's more, wedon't know how FDA might
(26:58):
put it into practice.
So you could look atthat as good, you could
look at it as bad.
It's certainly going to createa great deal of uncertainty.
You know, translating a, a pressrelease into predictable policy
is going to be challenging.
Simone Fishburn (27:14):
So what are your expectations?
What do we need toknow about Dr. Høeg
Steve Usdin (27:20):
So she is an MD, specializing in sports medicine,
she has a PhD in epidemiology.
She is never runa clinical trial.
She's never reviewed a drug.
She has no regulatoryexperience whatsoever.
She rose to prominenceas a COVID contrarian,
during the pandemic.
She advised Florida SurgeonGeneral Joseph Ladapo on
(27:40):
anti-vaccine policies thathave been heavily criticized
by public health experts.
She's played a leading roleas FDA's representative
to the ACIP that's theCDC's Advisory Committee
on immunization practices.
And which, in her capacitythere, she's challenged
the need for mandatoryvaccination of children.
(28:01):
She's called for changes tothe vaccine schedule that will
result in American childrenreceiving fewer vaccines.
As a Senior Advisor to FDACommissioner Makary, Høeg's
been closely involved withthe Commissioner National
Priority Voucher Program.
She's close to CBER Director,Vinay Prasad, and helped
write a memo, the one thatI mentioned earlier, uh,
(28:22):
announcing new vaccine policies.
Last week, every living FDACommissioner except one Stephen
Hahn, signed a commentarythat was published by the New
England Journal of Medicinethat condemned that memo
saying it will have disastrousconsequences for vaccine
development, and public health.
People I know who haveinteracted with Høeg at FDA,
say she's scientificallycurious um, in meetings she
(28:44):
asks probing questions or wantsto get into the details, but
they also say that she's anadvocate, not a regulator, that
she starts with conclusionsand cherry picks data to
get to the desired response.
Uh, and the FDA staff I'vespoken with say Høeg has
used that, that approach,and she's used observational
data in ways that aren'tscientifically appropriate.
To make assertionsabout drug safety.
(29:06):
One example, she was incharge of a review of
COVID vaccines that ledto restrictions that were
posed by longtime scientistsand civil servants at FDA.
Phil Krause, the Former DeputyHead of Vaccines at FDA, and
Luciana Borio, the FormerActing FDA Chief Scientist,
wrote a commentary that wepublished in BioCentury,
about the actions that Høegtook on COVID vaccines.
(29:28):
And they wrote that shiftingstandards and late stage
demands for new data based onfaulty scientific assumptions
have eroded trust, delayedaccess to important tools,
and discourage developers fromadvancing vaccine innovation.
I think we can expect thatHøeg's gonna move on MAHA
priorities, restricting accessto, SSRIs and other psychiatric
(29:50):
drugs for adolescents.
Taking action to reduce accessto puberty blockers, supporting
access to psychedelics.
And, and other, other steps Ithink that are, you know, on
the MAHA agenda, that's what wecan expect that she's gonna do.
Jeff Cranmer (30:04):
Steve, I'm just curious, has Bill Cassidy
made any comments aboutwhat's been happening at FDA?
Steve Usdin (30:11):
So you're, you're referring to Senator Cassidy,
who's the Chairman of theSenate Health Education Labor
Committee, he has made, publicstatements about the ACIP.
He's really kind of apoplectic,about what ACIP has done, in
terms of reducing access ofnewborns or recommendations
for newborns to get accessto hepatitis B vaccines.
(30:35):
It's a field that, Cassidyknows well, he's a physician,
and he treated a lotof hepatitis B patients.
And he's extremely concernedabout what ACIP has done.
I haven't heard him sayanything publicly about FDA.
Simone Fishburn (30:51):
Steve.
Well, I think, you know, wewould agree more with the
orthodoxy on vaccines thanlet's say on the MAHA agenda.
And I understand that Dr.
Høeg has sort of had a lot tosay about the COVID vaccines.
Also acknowledging thatthere are many people with
different views about that.
How relevant do you thinkher COVID vaccine position
(31:11):
is gonna be in her roleas the Head of CDER?
Is there daylight between those?
Steve Usdin (31:17):
Well, she doesn't regulate vaccines at CDER,
CDER doesn't regulate vaccines.
But I think that what itshows is how she thinks
about things, and the factthat, she's willing, and
eager really to take actionsand to take regulatory
actions based on ideologicalprinciples rather than, the,
(31:40):
uh, scientific consensus.
She's also acting, and thisis consistent with what
Marty Makary has been doingas FDA Commissioner, in the
absence of public advisorycommittees or other forms
that would create transparencyand accountability around
FDA's actions on topics thataffect public health and the
health of individual patients.
(32:02):
Not to mention the ability ofcompanies to develop drugs.
Jeff Cranmer (32:06):
Steve, a few other things are on
the agenda in Washington.
I don't know how much isgonna get done, we've been
talking a lot about thecomeback of the Biosecure Act.
Um, where does that stand?
Steve Usdin (32:18):
So, uh, the Biosecure Act, has been
included in the House versionof the National Defense
Authorization Act, the NDAA,which is a must pass bill.
It's a bill that's gonnabe passed very soon.
It's almost certain thatBiosecure 2.0 will be
included in the bill.
People may remember,we've talked about
(32:38):
this on the podcast.
The new version of Biosecurediffers from the version that
was pending last year becauserather than listing specific
companies, it creates a processfor the Administration right
now, the Trump Administrationto determine whether companies
are so-called biotechnologycompanies of concern.
(33:00):
And for those companies therewill be restrictions on US
companies or companies thatwanna sell their products in the
U.S. Accessing their services.
There's a five-yeargrandfathering period and
there's also limits on theeffectiveness of the, of
the sanctions, the effectof the sanctions on the
ability of companies to selldrugs in the United States.
(33:21):
A lot is gonna depend onhow the law is interpreted
or implemented by the,the Trump Administration.
Another bill that's almostcertain to be included in the
NDAA is something called theFight China Act, which imposes
sanctions on certain Chineseentities and restricts or
requires notification of USinvestments in specified high
(33:44):
risk technologies in China.
Basically it establishesan outbound investment
screening regime.
It isn't directly targeted atbiotech, and in fact, there
are provisions in it that, thatkind of provide a carve out
for certain research activitiesthat are conducted in China,
but nonetheless, it's likelyto impact of biotech companies.
(34:05):
Again, a lot of it's gonnadepend on how the Trump
Administration interprets it,but some kinds of collaboration,
some kinds of investments, incompanies in China that, use,
uh, advanced chipsets, forexample, that are developed
in China or use advancedAI systems that are Chinese
systems, could be, subject tonotification requirements or
(34:27):
even have to disinvest in inprojects in China, depending
on how the act is interpretedby the Administration.
Jeff Cranmer (34:35):
Okay, uh, you can read all of Steve's
stories, BioCenturypodcast.com.
We will be back next week.
Don't forget to subscribeto BioCentury This Week.
And check out the latestfrom our sister podcast
The BioCentury Show.
Selina sat down withBill Hinshaw to talk
(34:56):
precision medicine.
Bill is CEO of ForeBiotherapeutics.
Kendall Square Orchestraprovides the music for
BioCentury 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.
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