May 12, 2025 • 39 mins
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On this week's episode of the Business of Biotech, Dr. Mark Eisner, EVP and Chief Medical Officer at Vir Bio, talks about the company's post-COVID pivot into infectious diseases (Hepatitis Delta and Hepatitis B) and oncology (solid tumors), how he reprioritized the company's development candidates and assimilated Sanofi's acquired T cell engager platform, and his own transition from healthcare provider to clinical research.
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Episode Transcript
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Ben Comer (00:00):
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Welcome back to the Business ofBiotech.
(00:46):
I'm your host, Ben Comer, chiefEditor at Life Science Leader,
and I'm pleased to speak todaywith Dr.
Mark Eisner, Executive VicePresident and Chief Medical
Officer at Vir Biotechnology.
Mark received his medicaldegree from the University of
Pennsylvania, following abachelor's degree in human
biology at Stanford, and went onto complete a residency at the
(01:08):
University of California, SanFrancisco, where he stayed on as
a researcher and professor forthe next 25 plus years, and then
, in 2010, he decamped toGenentech and spent the next 10
years moving up the ranks tobecome senior vice president,
global Head of Immunology,infectious Disease and
Ophthalmology Development.
(01:28):
Since 2020, he's workedvariously as an Executive and
Chief Medical Officer and as aScientific Advisory Board member
across a handful of companiesbefore joining Vir Bio last year
.
I'm excited to speak with Marktoday about his career and Vir's
change in direction and to gethis insights on how to execute a
(01:48):
pivot in strategy anddevelopment focus.
Thanks for coming on thepodcast, Mark.
Mark Eisner, MD (01:53):
Thanks, Ben.
Thanks for inviting me.
Exciting excited to be here.
Ben Comer (01:58):
Mark, you worked in academic medicine at UCSF, as
I've just mentioned, for nearly30 years.
What precipitated your moveinto product development at
Genentech in 2010?
Mark Eisner, MD (02:11):
Yeah, no, it's a really good question.
I mean, when I think about mycareer and why I went into
medicine in the first place, Ioriginally thought I would be
taking care of patientsone-on-one and one-by-one, and I
did find that really verygratifying.
But once I was at UCSF and gotinvolved in clinical research, I
realized that it was reallyexciting to be able to answer
(02:35):
clinical questions that couldhelp large numbers of patients
as opposed to just patientsone-by-one, which is still, of
course, extremely important.
And then, when I got theopportunity to go to Genentech,
I got really excited because Ithought, you know, that would be
a place where I could make aneven bigger impact for patients
because of the resources and theability to test novel
(02:59):
therapeutics and really topotentially change how medicine
is practiced and help patientson a larger scale.
So that was why I made the moveand why I'm still really
excited to be in the biopharmaindustry.
Ben Comer (03:14):
Do you ever miss the one-on-one you know, as opposed
to the kind of once removedone-to-many versus the
one-to-one or no?
Mark Eisner, MD (03:23):
I do.
I mean, you know I think thereis something very special about
the interaction of a healthcareprovider with a patient and I
think you know there's somethingI do miss.
But you know I did do it for along time and I feel like a lot
of the problems that we'retrying to solve here at Vir do
ultimately come down to thinkingabout individual patients and
(03:44):
their diseases and thetherapeutics that we're trying
to develop.
So I always try to keep that inmind.
You know what the individualpatient would want or need.
Ben Comer (03:53):
Yeah, absolutely.
That makes a lot of sense.
And I do want to ask about someof Vir's development programs.
Hepatitis Delta was sort of anew one for me, so I'm looking
forward to you know learningsome more about about that
disease and what Vir is up to inthat category.
Um, you, you know, across youracademic career and your career
(04:13):
in industry, you've worked inpulmonary and respiratory
disease, now oncology,immunology, infectious disease.
Is there a disease ortherapeutic area that most
interests you personally, or isthere a through line that
connects those various fields ofresearch and development?
Mark Eisner, MD (04:33):
Yeah, no, I think my interest in pulmonary
critical care was partly because, despite the name, it does
involve diseases that affect allorgans, all part of the body,
and requires one to think verybroadly about physiology and
medicine.
So I've always been fascinatedby what causes different
(04:55):
diseases and how to treat them.
A disease like asthma orrheumatoid arthritis, where the
immune system is eitherresponding to abnormally to self
, either in an autoimmune way,or to an antigen, like an
environmental antigen in thecase of asthma.
(05:16):
Similarly, you know, aninfection like hepatitis delta
or cancer are both essentiallyforeign invaders and your immune
system is not alwaysfunctioning properly to treat
those.
So that's where I think there'sa commonality in what we're
trying to do here at Vir, whichis to leverage or power the
(05:38):
immune system to treat diseaseand transform the lives of
patients treat disease andtransform the lives of patients.
Ben Comer (05:50):
You joined Vir as EVP and chief medical officer last
June, relatively new on the job.
That was on the heels of astrategic reorganization that
closed a few R&D sites, led tosome significant layoffs at the
end of 2023, but that also ledto the acquisition of Sanofi's
via Amunix Pharma's threeclinical stage masked T-cell
(06:10):
engagers.
First off, what can you tell usabout the thinking or logic
behind the reorganization andacquisition and maybe, if you
could speak to the challengesthat come along with?
You know a pretty decent changein focus there.
Mark Eisner, MD (06:28):
Yeah, so great question.
So to go back a little bit, Imean Vir, I think, had a major
success rising to the challengeof COVID in the pandemic and
developed Sotrovimab in only 15months, which is really record
speed for discovering anddeveloping and getting to market
(06:49):
a new, totally noveltherapeutic for COVID.
But, as we all know, the viruscontinued to evolve and mutate
and Sotrovimab was no longereffective and is no longer being
used in the U.
S.
, certainly, certainly andminimally across the world.
So the company had to rethinkits priorities and its strategy.
(07:10):
And when I joined it was rightat a perfect time because we're
right in the middle of thosediscussions.
So looking at what are theprojects that we have that can
really move the needle forpatients and what else do we
need to bring in to make thepipeline successful.
So you know, really prioritizingthe programs for hepatitis
(07:32):
delta, tobevibart and elebsiranfor hepatitis delta, which is
going into Phase 3 imminently,thinking about our hepatitis B
program, and then deprioritizingsome of the other programs that
weren't really having the samepromise for patients.
And then the process that thecompany went through that led to
(07:53):
the Sanofi T-cell engagerplatform acquisition was one
where hundreds of companies andopportunities were looked at and
I think what we were hoping tofind and I think we did find is
something that had reallytransformative science, a big
potential to help patients,something that was right size
for a company of our size andscope to be able to develop.
(08:15):
And I think what wasparticularly wonderful is that
we also brought in about 50employees who were mostly former
Ammunex employees, includingthose who had developed the
technology, the masked TCEtechnology, those who developed
it and really were enabled us tohit the ground running with
(08:36):
those programs.
So I think that was a reallyexciting aspect of the deal.
Ben Comer (08:43):
Were you familiar, mark, with the science of T cell
engagers prior to starting workon this?
Was that something that youkind of knew and understood, or
did you have to learn itfollowing this move?
Mark Eisner, MD (08:57):
I would say yes and yes.
I mean I certainly was familiarwith T cell engagers, but I
also had to learn a lot in shortorder and I mean I think that's
part of what I love aboutworking in biotechnology is the
challenge, because you asked mebefore about different disease
areas and different programs,and you know, getting to work in
(09:17):
different areas and learn aboutthose is really exciting to me.
And you know also bringing inreal experts from Sanofi
formerly Amunix who can help usreally fully understand.
You know the platform and howwe're optimally going to develop
it.
Ben Comer (09:37):
Yeah, and following on that, the Amunix employees
came in.
You have an opportunity to workwith them.
But I'm curious, maybe from astep back, broader perspective,
as a new CMO coming into acompany to help lead the R&D
teams to success, you know, andprogressing, new modalities for
(10:00):
new indications, new indications.
How do you, I guess, how do youmotivate and invigorate the
teams that you manage, which are, you know, everyone's?
Mark Eisner, MD (10:11):
new to each other at this point.
Yeah, no, that's interesting, Ithink, first of all for me as a
leader.
I always keep the patient frontand center and try to think
about, you know, what problemare we trying to solve for the
patient?
You know, as we developtherapeutics for the patient,
and that's very grounding, and Ithink that's very inspiring for
(10:33):
people who work in R&D and inmy teams.
And you know to always try tobring it back to the
fundamentals, right?
What are we actually trying toachieve.
But I think also it's aroundtrying to create an environment
where people can do their bestthinking and their best work and
really contribute, and that'ssomething that is very very
important to me, and I've alwaysstrived to do and to create the
space where people do feelempowered and feel that they can
really contribute in their mostoptimal way, that's also a very
important element.
Ben Comer (11:13):
Are there any specific attributes or kind of
characteristics of that kind ofenvironment that you could
mention on kind of a groundfloor level?
You know?
What does that environment looklike?
How do you create it?
Mark Eisner, MD (11:21):
Yeah, great question.
I mean I think for me it'saround.
You know, if I'm leading a teamdiscussion, what I really like
to do, and I think is importantto do, is to really ask
questions and to make sureeverybody is heard from and
actually keep a bit back fromthat and be facilitating a
(11:41):
discussion.
And usually what happens whenone does that is you get people
to really express their ideasmore fully and usually the
solution suggests itself, youknow, during that process and as
opposed to one where it's verytop down and you come in and
(12:02):
just say this is how we're goingto do it.
You know that I think is verychallenging to not do for
someone like me, but I think youknow I've really that's a skill
I've really worked on and Ithink it's really helpful for
people to be able to reallycontribute their best ideas.
Ben Comer (12:19):
Yeah, and in terms of motivating a team, I'm sure
that you had to do some of thatin your academic career.
You know, prior to at Genentech, that you know that served you
well on that topic of gettingthe best and most out of your
(12:47):
colleagues now at Vier.
Mark Eisner, MD (12:50):
Yeah, I mean I guess you know, working in
academic medicine one always hasmedical students, residents,
fellows, people who are learning.
So you know part of the job isto teach people and, to you know
, find out what they know andyou know, help them learn what
they need to learn.
So I think that that's animportant skill I learned in
(13:10):
academic medicine.
But there are some pretty bigdifferences.
For example, you know, if I'mattending in the ICU and a
patient is having troublebreathing or low blood pressure,
I mean there are times whereyou just got to basically direct
people what to do.
There's not a lot of time toreact and that's not really a
great way typically to leadteams in biotech, pharma.
(13:32):
And I did have to learn thatactually, because I think things
are much more team oriented inthe biotechnology and pharma
world than there are in academia, where it can be very much
driven by an individualprincipal investigator or
attending physician and you knowyou kind of spend time
directing people and settingtheir priorities.
(13:53):
But in the biotech world Ilearned you got to be much more
of a coach and much more of amentor and really try to work in
that way and try to bring outfrom people.
You know their contributions,which of course could be
important in academic medicinetoo.
But I think, given the verycritical nature of
(14:14):
cross-functional teams in ourwork here, it's a different
skill set that's needed.
Ben Comer (14:20):
I want to get to hepatitis delta, but before I do
, we already spoke about thepivot, so to speak, or change in
focus and strategy at Vir.
This is something that happensat a lot of companies, if not
all, if they exist for longenough, right, and I wonder if,
(14:41):
if you ever went throughsomething like that at Genentech
, where there was a strategicreprioritization or, you know,
an acquisition that caused somechanges to the work that you
were doing, have you had to kindof work through that type of
situation before?
Mark Eisner, MD (14:57):
Yeah, of course I have, but I think it's it's
more.
I have, but I think it's more.
I mean, for example, we startedout as a product development
immunology and then we addedinfectious disease and added
ophthalmology, and that requiredsome reshuffling of priorities
and thinking.
You know, bringing verydifferent groups together.
(15:19):
I think what's different aboutwhat we've had to do at Vir is,
as a smaller company and as abiotech company, it's a pretty
big pivot to go from infectiousdisease to infectious disease
and oncology.
What I think has helped us isthe fact that the underlying
need to focus on the immunesystem and how we target it to
(15:41):
treat either an infectious agentlike Delta or harnessing
T-cells to fight cancer.
There's a thematic connectionthere, I think.
Also, fundamentally, at thecore of Vir's technology is
antibody engineering, which Ithink is a super important
capability.
That bringing in the T-cellengager platform allows us to
(16:03):
think about the next generationof targets.
But there's no question thatreshaping a portfolio and
reframing the direction of acompany, particularly one our
size, is very challenging, and Ithink the fact that we were
able to bring in the Sanofiemployees and integrate them
into our teams is superimportant, because it just
(16:24):
allowed us not to miss a beat.
Ben Comer (16:27):
Did those employees actually relocate, and are they,
you know, in the officephysically or did they kind of
stay where they were and youknow you're working with them
remotely?
Mark Eisner, MD (16:38):
Yeah, well, fortunately for us, they were
located in South San Francisco,about seven miles away.
Oh perfect, we've brought allthose new we call them Virites"
new Virites into the office, soeverybody's here and it's been
really, really nice in that way.
Ben Comer (16:56):
You mentioned the antibody platform, and so maybe
we'll just take a minute todiscuss this.
Vir has two discrete platformsfor drug discovery and
development the data AIstructure and antibody or dAIsY
platform, and then the PRO- XTENmasking platform, the T-cell
(17:17):
engager platform that camethrough the Sanofi Amunix deal.
Would you mind just telling uswhat's unique about each of
those platforms?
Mark Eisner, MD (17:28):
Sure Happy to do that.
So dAIsY is an AI-basedplatform that allows us to
really accelerate and optimizethe engineering of antibodies.
So instead of taking a newantibody candidate and doing
mutations one by one, by one byone, which is a gargantuan task,
(17:52):
it allows us to leverageextensive databases on protein
sequences and develop andprioritize a series of
candidates that we can then testto optimize our antibodies.
So it greatly accelerates andoptimizes the way we engineer
antibodies.
The PRO-XTEN platform is amasking technology that uses
(18:19):
large unstructured hydrophilicpolypeptides with protein
cleavable linkers to mask boththe T-cell engaging arm and the
tumor's binding arm of theseT-cell engagers to allow us to
achieve a really much bettertherapeutic index, in other
words, better efficacy withadequate safety.
(18:42):
So they're very differentapproaches and very unique from
one another, as you say, but Ithink what's really exciting is
that they're complementary too,because we can use our antibody
engineering technology in dAIsYto work on the next generation
of masked TCE candidates, usingthe masking and the linker
(19:03):
technology brought through theplatform.
Ben Comer (19:07):
I see so you're not necessarily deprioritizing the
dAIsY platform.
It's still very much a playerin your current development
efforts.
Mark Eisner, MD (19:16):
Absolutely.
I mean, they both are veryimportant complementary
technologies.
So we're not deprioritizingeither, we're working on both of
them.
Ben Comer (19:25):
And you know, because you mentioned it and it's so
much in the news here recentlyand I expect will be in the near
future AI, what you know, whatis your kind of read on?
You know the performance of AIand the dAIsY platform.
You know, have you gotten to apoint at Vir yet where you know
(19:47):
AI has been, you could say youknow, extremely helpful in
actually getting a candidate,you know, from that discovery
phase testing and into theclinic?
I'll leave it open for you.
You know, what would you sayabout?
You say about the role of AI,at least in discovery efforts?
Mark Eisner, MD (20:05):
Right.
So the specific role of AI inthe dAIsY platform, I mean it
really does yield tangibleadvances for us because we can
greatly accelerate and optimizethe discovery of an antibody and
the nomination of it as a leadcandidate.
So that's very important, Ithink.
(20:27):
In terms of other uses of AI, Imean we are exploring how we
can leverage AI in differentaspects of what we do.
I mean, I think it's a littleearly to comment in a lot of
detail there, but it's clearlysomething that we're greatly
interested in and there are many, many different applications
(20:47):
that one could imagine.
Ben Comer (20:49):
With something like the dAIsY platform?
Are you kind of in an iterativeway, you know, adding
additional components of AI,reviewing new AI technologies to
you know, consider to bring in?
Or do you have your kind ofstack, now that you're set with,
the platform is built and it'sworking, accomplishing what do
(21:11):
you want it to accomplish?
I'm just curious about, as thefield, which is rapidly evolving
changes, what does thatinterplay look like in terms of
the dAIsY platform and, you know, emerging tech?
Mark Eisner, MD (21:24):
Sure, so I think we are with that
particular platform.
We are constantly evaluatingthe results and looking at ways
to improve how it works.
So in that sense, it's alwaysgoing to be an iterative,
evolving way of working withthat platform.
So I think that's important tonote in terms of we are very
(21:51):
committed generally in how weapply data sciences in all
aspects of what we do.
It's a very rigorous processhere.
We are always thinking abouthow else can we do things
smarter, better with datatechnologies, so it is a pretty
important focus for the company.
Ben Comer (22:12):
Excellent.
I want to get now to hepatitisdelta, which didn't, at least
for me, have the same kind ofname recognition or visibility
generally as hepatitis C or hepB, for example.
You are on the cusp ofcommencing a phase three trial
in hepatitis delta.
Can you tell us a little bitmore about the disease and the
(22:37):
unmet need that it represents?
Mark Eisner, MD (22:38):
Sure.
So, as you say, I meanhepatitis B is a much more
common disease.
I mean it affects more than aquarter of a billion people
around the globe.
Hepatitis Delta is a rare liverdisease.
It's an RNA virus that requiresco-infection with hepatitis B,
(23:01):
either previously or at the sametime, because hepatitis delta
uses the hepatitis B surfaceantigen as part of its life
cycle to construct new virions,new infectious particles.
So there is a close interplaybetween delta and hepatitis B.
Where I think the unmet need isit's a very, very severe liver
(23:24):
disease, even though it's a muchless common one.
It can progress to cirrhosis,liver failure, liver cancer and
even death rapidly within a fiveto 10-year period.
So it's a very, verydevastating infection and
there's not much to offer.
In the U.
S.
there's no approved therapiesfor hepatitis delta.
(23:45):
In Europe there is one approvedtherapy, bulevirtide or
Hepcludex, which is an advance,but still, you know, there's
great need for better treatmentsfor patients.
Ben Comer (23:59):
Do you know why that one was never approved in the US
?
Mark Eisner, MD (24:02):
Well, what we know is that Gilead received a
complete response letter fromthe FDA.
There's something to do withthe manufacturing of the product
.
We do know that it's a dailyself-injection Patients need to
reconstitute a dry powder andself-inject.
There's not a lot more detailthat's been disclosed by Gilead
(24:24):
and we also don't know exactlywhat the timing is for or
whether they will resubmit toaddress the Complete Response
Letter in the U.
S.
In Europe it is being used.
I mean, it's a drug that'sdefinitely in advance on current
standard of care.
But when you think about it,bulevirtide achieves about a 12%
(24:48):
complete viral suppression, orwhat we call target not detected
no detection of the virus atall at 48 weeks, which is an
advance over zero, which is whatpatients were facing before.
With our regimen of tobevibartand elebsiran, the combination
regimen, we believe we can treatthe majority of patients and
(25:10):
get them to target not detectedor complete viral suppression.
Ben Comer (25:16):
And Alnylam is a partner on your hepatitis delta
and hepatitis B clinicalprograms.
What can you say about how thatpartnership came about?
Mark Eisner, MD (25:27):
Yeah, I mean Alnylam discovered elebsiran,
which is the siRNA component ofour regimen, so in that sense
it's very important.
I think it speaks to theimportance of partnerships in
finding external innovation.
Another example is the Amunix /Sanofi external innovation that
(25:48):
we brought in and just I thinkhow important partnering is for
biopharma generally, but Virspecifically, and we're very
excited to have elebsiran aspart of our regimen for
hepatitis delta and hepatitis B.
Ben Comer (26:04):
Is there anything else?
I know you have a partnershipwith GSK and respiratory disease
.
Is there anything else youwould say, Mark, about Vir's
more broadly I guess approach topartnering in terms of, you
know, partner selection andtiming.
Mark Eisner, MD (26:20):
Yeah, so absolutely.
I mean, I think it's maybe alittle bit under-recognized in
the biopharma industry or maybein the general public about how
critical partnering is, both tobring in external innovation,
and part of a competitiveadvantage we have at Vir is, I
think we are able to see whatgreat scientific innovation
(26:40):
looks like, and that would bethe example would be the TCE
platform that we brought in butalso to work with a partner like
GSK, where you know, Vir wasable to discover and bring this
sotrovimab to patients in 15months, but then to have a
partner like GSK, with a globalfootprint, with the expertise in
(27:01):
infectious and respiratorydisease marketing, and to work
together to get this drug to thepatients during a pandemic and,
just, you know, treat and save,you know, many, many, many
lives.
I think that was, you know, atestimony to how well Vir was
able to identify and work with abig pharma partner like GSK.
Ben Comer (27:23):
Yeah, and we talked about Vir's new focus, which is
infectious disease as well asoncology.
So I'd like to ask now aboutthe oncology indications that
you're pursuing and what kindsof milestones that you're
currently working toward inoncology.
Mark Eisner, MD (27:41):
Sure.
So I think maybe it's helpfulto start with what is the
problem statement?
So the problem statement forunmasked T-cell engagers, which
are approved for various targetsin the liquid tumor hematology
space, but for solid tumorsthey've just been too toxic.
Like unmasked HER2 orPSMA-directed T-cell engagers
(28:04):
have caused cytokine releasesyndrome where patients develop
respiratory compromise,hypotension, shock and, you know
, haven't been viabletherapeutics for solid tumors
because of the toxicity.
So the technology of themasking, with the PRO-XTEN
platform, which allows us tohave molecules that are masked
(28:30):
in the normal tissue in theblood, so pretty much inactive,
but when they get into the tumor, microenvironment proteases in
the tumor microenvironmentcleave off the masks and
activate the molecules, allowingthem to form an immune synapse
between the T cell and the tumorcell and kill the tumor cell
(28:51):
very effectively.
So that's, I think,fundamentally what's exciting
about the masking technology andhow it can improve therapeutic
index.
So we have three clinical stageprograms.
One is the 5818 program Sorry,yeah, 5818 program which is the
HER2-directed T-cell engagerwhich is potentially applicable
(29:16):
to a variety of HER2-positivetumors, including colorectal
cancer, where we presented someexciting data at a well and
we're doing a basket trial,phase one dose escalation trial,
where we are testing it out indifferent tumor types.
(29:38):
The 5500 program is directed atPSMA, which is an important
target for prostate cancer.
So we're currently testing thisin metastatic,
castration-resistant prostatecancer and we're escalating the
dose there, both in Q weekly andQ3 weekly scenarios, because we
(30:04):
want to get to a point where wecan potentially treat those
patients with metastaticprostate cancer.
And then the last one is ourTCE targeting EGFR, which is a
very, very broad antigen inmultiple tumor types, including
non-small cell lung cancer, headand neck cancer, and we are
(30:26):
planning to start phase onetrials in the first half of this
year.
Ben Comer (30:32):
Excellent.
I wanted to ask a questionabout the HER2 target.
I was speaking with the CEO ofa smaller biotech that's working
in oncology and a point that hemade to me was that the
fundamental problem in cancer istherapies being able to attack
(30:53):
cancer cells but not attackhealthy cells.
And this company is working ona kind of logic gating
technology that will, you know,essentially include multiple
receptors turned on and off,according to you know, sensing a
healthy cell versus a cancercell.
And the point that he made tome was that a target like HER2
(31:15):
is becoming increasingly crowded, people throwing a lot of
different modalities at it,because it's a target where, in
a sense, I guess, maybe yourtherapy can kill somewhat
indiscriminately.
Now, what you're saying with themasking technology adds some
nuance to that.
But I wonder, you know, is that, you know thinking about, you
(31:39):
know, the next big big leap incancer therapeutics?
Is it, you know, being able tokill cancer cells, kill cancer
without the resulting toxicities?
Do you see that as the currentlimitation?
Or would you give anotherexplanation for, you know, for
what's needed, I guess, for thenext big cancer breakthrough?
Mark Eisner, MD (32:02):
Yeah, I think that's an excellent question and
I do think that the specificityis super important here and the
masking in particular whichallows this mass T-cell engager
approach to work, because itallows us to dose escalate to
(32:22):
doses that can start to beeffective in killing the tumor.
So in HER2, it can bind theHER2 positive tumor cell and the
T cell and promote the T cellkilling of the HER2 positive
tumor cell.
Normal tissues like heart andlung tissues can express HER2.
So, to your point, we don'twant to activate the T cell
(32:45):
engager in normal lung tissue,normal heart tissue at all,
because that just bringstoxicity.
So I think what we've been ableto show so far in our public
data disclosures is that we candose these mast molecules, these
mast T-cell engagers, highenough to start killing tumors
(33:06):
while maintaining an adequatesafety, so only sort of minimal
cytokine release syndrome.
For example, one of the patientswe presented was a woman who
had very advanced breast cancerthat was infiltrating her skin
and she had been treated withnine prior lines of treatment
including Enhertu, which is arecently approved HER2-directed
(33:28):
treatment, Then you canliterally see visually this
tumor just clear from her skinwith 5818 over a 5 to 10-week
period.
it unequivocally had clinicalactivity in this patient who had
been through multiple, multipleother options.
(33:48):
And so I think it's case andback to our earlier discussion
around individual patients.
I mean we obviously need todemonstrate the effects, that
these are safe and effective inpopulations of patients, but
sometimes it's a patient likethat that really informs us that
we're on the right track with atreatment right.
And you know we have otherpatients as well.
(34:09):
There's a colorectal patientwho got this treatment right and
you know we have other patientsas well.
There's a colorectal patientwho got this treatment who's
been on drug for more than 18months and has been very, very
stable, and another prostatecancer patient on the 5500
program where you know they'vehad a very sustained suppression
of their PSA, you knowresolution of bony lesions on
(34:29):
MRI.
And it's patients like thatthat really tell us that we're
on the right course and I thinkalso for the teams it's just
really inspiring to see thosepatients kind of get back to
more normal lives and it justmakes us want to keep working on
this and advance the programs.
Ben Comer (34:49):
Looking forward into the future.
Now Vir has completed thispivot.
You're focused on oncology,you're focused on hepatitis B,
hepatitis delta.
What, I guess, are your topgoals for 2025 and maybe 2026?
And if you, would you know,what do you see as the biggest
(35:10):
challenge?
Mark Eisner, MD (35:11):
Sure.
So I mean 2025 for us is a veryimportant year for execution.
I mean, on the hepatitis deltaprogram, we are starting three
pivotal trials and we're goingto be enrolling our first
patient in the first half ofthis year.
So that's a laser focus for usand the team is getting those
(35:34):
trials up and running.
On the T cell engager side,it's continued dose escalation
for the HER2 and PSMA programsand getting the EGFR program
into the clinic, continuing toshow what efficacy we can get
with acceptable safety, minimalCRS and other acceptable safety
(35:57):
profiles.
So it's around really executingon those programs.
I think also on the researchside, it's using the antibody
discovery platform with dAIsYand the masked PRO-EXTEN
platform to work on the nextgeneration of tumor targets and
to work on, you know, in theresearch discovery space.
(36:17):
You know what's going to comenext, you know, besides the
clinical stage assets that wecurrently have.
And then the last thing I wouldmention is we are, you know,
going to have functional curedata for hepatitis B, a March
phase two study coming inquarter two of this year, and so
(36:38):
we're really excited about that.
The data at the end oftreatment were really exciting,
and what we have said is we'relooking for a partner to advance
that one into furtherdevelopment, because it's a
large program, it's going torequire a lot of resources and
that's a place where I think astrategic partner to develop
that globally will really reallybe important for us to find.
Ben Comer (37:02):
Yeah, and that raises a new question for me, which is
when do you get started on theglobal development efforts?
Do you, you know, is it afterthis next kind of phase readout,
and then you decide, yes, we'regoing for you know, we're going
to look for a partner, we'regoing to begin development
efforts elsewhere.
Maybe you're already in, youknow multi center locations
(37:25):
around the world.
I'm not sure, but can you giveme a sense of your kind of
global ambitions for thatproduct, given you know that
it's a really large indication?
Mark Eisner, MD (37:53):
Sure, so yes, so we certainly have started
planning of what the next phaseof clinical development would
look like the trial designs withthe next regulatory
interactions that we would have,and we've started thinking
about and talking to prospectivepartners.
I think this will be a processover time where our aspiration
if the data can support thecontinued development of the
functional cure point, which is,of course, fundamental we need
that would be to find a partnerwho would then work through that
with us and then ultimatelytake over that phase of
(38:14):
development for B, while wefully own and develop the
hepatitis delta trials ourselves.
Ben Comer (38:23):
Got it All right.
That is Dr Mark Eisner,executive vice president and
chief medical officer at VeerBiotechnology.
I'm Ben Comer and you've justlistened to the Business of
Biotech.
Find us and subscribe.
Anywhere you listen to podcasts, and be sure to check out the
new weekly videocasts of theseconversations every Monday under
the Business of Biotech tab atlifescienceleader.
(38:45):
com.
We'll see you next week andthank you for listening.
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Welcome back to the Business ofBiotech.
(00:46):
I'm your host, Ben Comer, chiefEditor at Life Science Leader,
and I'm pleased to speak todaywith Dr.
Mark Eisner, Executive VicePresident and Chief Medical
Officer at Vir Biotechnology.
Mark received his medicaldegree from the University of
Pennsylvania, following abachelor's degree in human
biology at Stanford, and went onto complete a residency at the
(01:08):
University of California, SanFrancisco, where he stayed on as
a researcher and professor forthe next 25 plus years, and then
, in 2010, he decamped toGenentech and spent the next 10
years moving up the ranks tobecome senior vice president,
global Head of Immunology,infectious Disease and
Ophthalmology Development.
(01:28):
Since 2020, he's workedvariously as an Executive and
Chief Medical Officer and as aScientific Advisory Board member
across a handful of companiesbefore joining Vir Bio last year
.
I'm excited to speak with Marktoday about his career and Vir's
change in direction and to gethis insights on how to execute a
(01:48):
pivot in strategy anddevelopment focus.
Thanks for coming on thepodcast, Mark.
Mark Eisner, MD (01:53):
Thanks, Ben.
Thanks for inviting me.
Exciting excited to be here.
Ben Comer (01:58):
Mark, you worked in academic medicine at UCSF, as
I've just mentioned, for nearly30 years.
What precipitated your moveinto product development at
Genentech in 2010?
Mark Eisner, MD (02:11):
Yeah, no, it's a really good question.
I mean, when I think about mycareer and why I went into
medicine in the first place, Ioriginally thought I would be
taking care of patientsone-on-one and one-by-one, and I
did find that really verygratifying.
But once I was at UCSF and gotinvolved in clinical research, I
realized that it was reallyexciting to be able to answer
(02:35):
clinical questions that couldhelp large numbers of patients
as opposed to just patientsone-by-one, which is still, of
course, extremely important.
And then, when I got theopportunity to go to Genentech,
I got really excited because Ithought, you know, that would be
a place where I could make aneven bigger impact for patients
because of the resources and theability to test novel
(02:59):
therapeutics and really topotentially change how medicine
is practiced and help patientson a larger scale.
So that was why I made the moveand why I'm still really
excited to be in the biopharmaindustry.
Ben Comer (03:14):
Do you ever miss the one-on-one you know, as opposed
to the kind of once removedone-to-many versus the
one-to-one or no?
Mark Eisner, MD (03:23):
I do.
I mean, you know I think thereis something very special about
the interaction of a healthcareprovider with a patient and I
think you know there's somethingI do miss.
But you know I did do it for along time and I feel like a lot
of the problems that we'retrying to solve here at Vir do
ultimately come down to thinkingabout individual patients and
(03:44):
their diseases and thetherapeutics that we're trying
to develop.
So I always try to keep that inmind.
You know what the individualpatient would want or need.
Ben Comer (03:53):
Yeah, absolutely.
That makes a lot of sense.
And I do want to ask about someof Vir's development programs.
Hepatitis Delta was sort of anew one for me, so I'm looking
forward to you know learningsome more about about that
disease and what Vir is up to inthat category.
Um, you, you know, across youracademic career and your career
(04:13):
in industry, you've worked inpulmonary and respiratory
disease, now oncology,immunology, infectious disease.
Is there a disease ortherapeutic area that most
interests you personally, or isthere a through line that
connects those various fields ofresearch and development?
Mark Eisner, MD (04:33):
Yeah, no, I think my interest in pulmonary
critical care was partly because, despite the name, it does
involve diseases that affect allorgans, all part of the body,
and requires one to think verybroadly about physiology and
medicine.
So I've always been fascinatedby what causes different
(04:55):
diseases and how to treat them.
A disease like asthma orrheumatoid arthritis, where the
immune system is eitherresponding to abnormally to self
, either in an autoimmune way,or to an antigen, like an
environmental antigen in thecase of asthma.
(05:16):
Similarly, you know, aninfection like hepatitis delta
or cancer are both essentiallyforeign invaders and your immune
system is not alwaysfunctioning properly to treat
those.
So that's where I think there'sa commonality in what we're
trying to do here at Vir, whichis to leverage or power the
(05:38):
immune system to treat diseaseand transform the lives of
patients treat disease andtransform the lives of patients.
Ben Comer (05:50):
You joined Vir as EVP and chief medical officer last
June, relatively new on the job.
That was on the heels of astrategic reorganization that
closed a few R&D sites, led tosome significant layoffs at the
end of 2023, but that also ledto the acquisition of Sanofi's
via Amunix Pharma's threeclinical stage masked T-cell
(06:10):
engagers.
First off, what can you tell usabout the thinking or logic
behind the reorganization andacquisition and maybe, if you
could speak to the challengesthat come along with?
You know a pretty decent changein focus there.
Mark Eisner, MD (06:28):
Yeah, so great question.
So to go back a little bit, Imean Vir, I think, had a major
success rising to the challengeof COVID in the pandemic and
developed Sotrovimab in only 15months, which is really record
speed for discovering anddeveloping and getting to market
(06:49):
a new, totally noveltherapeutic for COVID.
But, as we all know, the viruscontinued to evolve and mutate
and Sotrovimab was no longereffective and is no longer being
used in the U.
S.
, certainly, certainly andminimally across the world.
So the company had to rethinkits priorities and its strategy.
(07:10):
And when I joined it was rightat a perfect time because we're
right in the middle of thosediscussions.
So looking at what are theprojects that we have that can
really move the needle forpatients and what else do we
need to bring in to make thepipeline successful.
So you know, really prioritizingthe programs for hepatitis
(07:32):
delta, tobevibart and elebsiranfor hepatitis delta, which is
going into Phase 3 imminently,thinking about our hepatitis B
program, and then deprioritizingsome of the other programs that
weren't really having the samepromise for patients.
And then the process that thecompany went through that led to
(07:53):
the Sanofi T-cell engagerplatform acquisition was one
where hundreds of companies andopportunities were looked at and
I think what we were hoping tofind and I think we did find is
something that had reallytransformative science, a big
potential to help patients,something that was right size
for a company of our size andscope to be able to develop.
(08:15):
And I think what wasparticularly wonderful is that
we also brought in about 50employees who were mostly former
Ammunex employees, includingthose who had developed the
technology, the masked TCEtechnology, those who developed
it and really were enabled us tohit the ground running with
(08:36):
those programs.
So I think that was a reallyexciting aspect of the deal.
Ben Comer (08:43):
Were you familiar, mark, with the science of T cell
engagers prior to starting workon this?
Was that something that youkind of knew and understood, or
did you have to learn itfollowing this move?
Mark Eisner, MD (08:57):
I would say yes and yes.
I mean I certainly was familiarwith T cell engagers, but I
also had to learn a lot in shortorder and I mean I think that's
part of what I love aboutworking in biotechnology is the
challenge, because you asked mebefore about different disease
areas and different programs,and you know, getting to work in
(09:17):
different areas and learn aboutthose is really exciting to me.
And you know also bringing inreal experts from Sanofi
formerly Amunix who can help usreally fully understand.
You know the platform and howwe're optimally going to develop
it.
Ben Comer (09:37):
Yeah, and following on that, the Amunix employees
came in.
You have an opportunity to workwith them.
But I'm curious, maybe from astep back, broader perspective,
as a new CMO coming into acompany to help lead the R&D
teams to success, you know, andprogressing, new modalities for
(10:00):
new indications, new indications.
How do you, I guess, how do youmotivate and invigorate the
teams that you manage, which are, you know, everyone's?
Mark Eisner, MD (10:11):
new to each other at this point.
Yeah, no, that's interesting, Ithink, first of all for me as a
leader.
I always keep the patient frontand center and try to think
about, you know, what problemare we trying to solve for the
patient?
You know, as we developtherapeutics for the patient,
and that's very grounding, and Ithink that's very inspiring for
(10:33):
people who work in R&D and inmy teams.
And you know to always try tobring it back to the
fundamentals, right?
What are we actually trying toachieve.
But I think also it's aroundtrying to create an environment
where people can do their bestthinking and their best work and
really contribute, and that'ssomething that is very very
important to me, and I've alwaysstrived to do and to create the
space where people do feelempowered and feel that they can
really contribute in their mostoptimal way, that's also a very
important element.
Ben Comer (11:13):
Are there any specific attributes or kind of
characteristics of that kind ofenvironment that you could
mention on kind of a groundfloor level?
You know?
What does that environment looklike?
How do you create it?
Mark Eisner, MD (11:21):
Yeah, great question.
I mean I think for me it'saround.
You know, if I'm leading a teamdiscussion, what I really like
to do, and I think is importantto do, is to really ask
questions and to make sureeverybody is heard from and
actually keep a bit back fromthat and be facilitating a
(11:41):
discussion.
And usually what happens whenone does that is you get people
to really express their ideasmore fully and usually the
solution suggests itself, youknow, during that process and as
opposed to one where it's verytop down and you come in and
(12:02):
just say this is how we're goingto do it.
You know that I think is verychallenging to not do for
someone like me, but I think youknow I've really that's a skill
I've really worked on and Ithink it's really helpful for
people to be able to reallycontribute their best ideas.
Ben Comer (12:19):
Yeah, and in terms of motivating a team, I'm sure
that you had to do some of thatin your academic career.
You know, prior to at Genentech, that you know that served you
well on that topic of gettingthe best and most out of your
(12:47):
colleagues now at Vier.
Mark Eisner, MD (12:50):
Yeah, I mean I guess you know, working in
academic medicine one always hasmedical students, residents,
fellows, people who are learning.
So you know part of the job isto teach people and, to you know
, find out what they know andyou know, help them learn what
they need to learn.
So I think that that's animportant skill I learned in
(13:10):
academic medicine.
But there are some pretty bigdifferences.
For example, you know, if I'mattending in the ICU and a
patient is having troublebreathing or low blood pressure,
I mean there are times whereyou just got to basically direct
people what to do.
There's not a lot of time toreact and that's not really a
great way typically to leadteams in biotech, pharma.
(13:32):
And I did have to learn thatactually, because I think things
are much more team oriented inthe biotechnology and pharma
world than there are in academia, where it can be very much
driven by an individualprincipal investigator or
attending physician and you knowyou kind of spend time
directing people and settingtheir priorities.
(13:53):
But in the biotech world Ilearned you got to be much more
of a coach and much more of amentor and really try to work in
that way and try to bring outfrom people.
You know their contributions,which of course could be
important in academic medicinetoo.
But I think, given the verycritical nature of
(14:14):
cross-functional teams in ourwork here, it's a different
skill set that's needed.
Ben Comer (14:20):
I want to get to hepatitis delta, but before I do
, we already spoke about thepivot, so to speak, or change in
focus and strategy at Vir.
This is something that happensat a lot of companies, if not
all, if they exist for longenough, right, and I wonder if,
(14:41):
if you ever went throughsomething like that at Genentech
, where there was a strategicreprioritization or, you know,
an acquisition that caused somechanges to the work that you
were doing, have you had to kindof work through that type of
situation before?
Mark Eisner, MD (14:57):
Yeah, of course I have, but I think it's it's
more.
I have, but I think it's more.
I mean, for example, we startedout as a product development
immunology and then we addedinfectious disease and added
ophthalmology, and that requiredsome reshuffling of priorities
and thinking.
You know, bringing verydifferent groups together.
(15:19):
I think what's different aboutwhat we've had to do at Vir is,
as a smaller company and as abiotech company, it's a pretty
big pivot to go from infectiousdisease to infectious disease
and oncology.
What I think has helped us isthe fact that the underlying
need to focus on the immunesystem and how we target it to
(15:41):
treat either an infectious agentlike Delta or harnessing
T-cells to fight cancer.
There's a thematic connectionthere, I think.
Also, fundamentally, at thecore of Vir's technology is
antibody engineering, which Ithink is a super important
capability.
That bringing in the T-cellengager platform allows us to
(16:03):
think about the next generationof targets.
But there's no question thatreshaping a portfolio and
reframing the direction of acompany, particularly one our
size, is very challenging, and Ithink the fact that we were
able to bring in the Sanofiemployees and integrate them
into our teams is superimportant, because it just
(16:24):
allowed us not to miss a beat.
Ben Comer (16:27):
Did those employees actually relocate, and are they,
you know, in the officephysically or did they kind of
stay where they were and youknow you're working with them
remotely?
Mark Eisner, MD (16:38):
Yeah, well, fortunately for us, they were
located in South San Francisco,about seven miles away.
Oh perfect, we've brought allthose new we call them Virites"
new Virites into the office, soeverybody's here and it's been
really, really nice in that way.
Ben Comer (16:56):
You mentioned the antibody platform, and so maybe
we'll just take a minute todiscuss this.
Vir has two discrete platformsfor drug discovery and
development the data AIstructure and antibody or dAIsY
platform, and then the PRO- XTENmasking platform, the T-cell
(17:17):
engager platform that camethrough the Sanofi Amunix deal.
Would you mind just telling uswhat's unique about each of
those platforms?
Mark Eisner, MD (17:28):
Sure Happy to do that.
So dAIsY is an AI-basedplatform that allows us to
really accelerate and optimizethe engineering of antibodies.
So instead of taking a newantibody candidate and doing
mutations one by one, by one byone, which is a gargantuan task,
(17:52):
it allows us to leverageextensive databases on protein
sequences and develop andprioritize a series of
candidates that we can then testto optimize our antibodies.
So it greatly accelerates andoptimizes the way we engineer
antibodies.
The PRO-XTEN platform is amasking technology that uses
(18:19):
large unstructured hydrophilicpolypeptides with protein
cleavable linkers to mask boththe T-cell engaging arm and the
tumor's binding arm of theseT-cell engagers to allow us to
achieve a really much bettertherapeutic index, in other
words, better efficacy withadequate safety.
(18:42):
So they're very differentapproaches and very unique from
one another, as you say, but Ithink what's really exciting is
that they're complementary too,because we can use our antibody
engineering technology in dAIsYto work on the next generation
of masked TCE candidates, usingthe masking and the linker
(19:03):
technology brought through theplatform.
Ben Comer (19:07):
I see so you're not necessarily deprioritizing the
dAIsY platform.
It's still very much a playerin your current development
efforts.
Mark Eisner, MD (19:16):
Absolutely.
I mean, they both are veryimportant complementary
technologies.
So we're not deprioritizingeither, we're working on both of
them.
Ben Comer (19:25):
And you know, because you mentioned it and it's so
much in the news here recentlyand I expect will be in the near
future AI, what you know, whatis your kind of read on?
You know the performance of AIand the dAIsY platform.
You know, have you gotten to apoint at Vir yet where you know
(19:47):
AI has been, you could say youknow, extremely helpful in
actually getting a candidate,you know, from that discovery
phase testing and into theclinic?
I'll leave it open for you.
You know, what would you sayabout?
You say about the role of AI,at least in discovery efforts?
Mark Eisner, MD (20:05):
Right.
So the specific role of AI inthe dAIsY platform, I mean it
really does yield tangibleadvances for us because we can
greatly accelerate and optimizethe discovery of an antibody and
the nomination of it as a leadcandidate.
So that's very important, Ithink.
(20:27):
In terms of other uses of AI, Imean we are exploring how we
can leverage AI in differentaspects of what we do.
I mean, I think it's a littleearly to comment in a lot of
detail there, but it's clearlysomething that we're greatly
interested in and there are many, many different applications
(20:47):
that one could imagine.
Ben Comer (20:49):
With something like the dAIsY platform?
Are you kind of in an iterativeway, you know, adding
additional components of AI,reviewing new AI technologies to
you know, consider to bring in?
Or do you have your kind ofstack, now that you're set with,
the platform is built and it'sworking, accomplishing what do
(21:11):
you want it to accomplish?
I'm just curious about, as thefield, which is rapidly evolving
changes, what does thatinterplay look like in terms of
the dAIsY platform and, you know, emerging tech?
Mark Eisner, MD (21:24):
Sure, so I think we are with that
particular platform.
We are constantly evaluatingthe results and looking at ways
to improve how it works.
So in that sense, it's alwaysgoing to be an iterative,
evolving way of working withthat platform.
So I think that's important tonote in terms of we are very
(21:51):
committed generally in how weapply data sciences in all
aspects of what we do.
It's a very rigorous processhere.
We are always thinking abouthow else can we do things
smarter, better with datatechnologies, so it is a pretty
important focus for the company.
Ben Comer (22:12):
Excellent.
I want to get now to hepatitisdelta, which didn't, at least
for me, have the same kind ofname recognition or visibility
generally as hepatitis C or hepB, for example.
You are on the cusp ofcommencing a phase three trial
in hepatitis delta.
Can you tell us a little bitmore about the disease and the
(22:37):
unmet need that it represents?
Mark Eisner, MD (22:38):
Sure.
So, as you say, I meanhepatitis B is a much more
common disease.
I mean it affects more than aquarter of a billion people
around the globe.
Hepatitis Delta is a rare liverdisease.
It's an RNA virus that requiresco-infection with hepatitis B,
(23:01):
either previously or at the sametime, because hepatitis delta
uses the hepatitis B surfaceantigen as part of its life
cycle to construct new virions,new infectious particles.
So there is a close interplaybetween delta and hepatitis B.
Where I think the unmet need isit's a very, very severe liver
(23:24):
disease, even though it's a muchless common one.
It can progress to cirrhosis,liver failure, liver cancer and
even death rapidly within a fiveto 10-year period.
So it's a very, verydevastating infection and
there's not much to offer.
In the U.
S.
there's no approved therapiesfor hepatitis delta.
(23:45):
In Europe there is one approvedtherapy, bulevirtide or
Hepcludex, which is an advance,but still, you know, there's
great need for better treatmentsfor patients.
Ben Comer (23:59):
Do you know why that one was never approved in the US
?
Mark Eisner, MD (24:02):
Well, what we know is that Gilead received a
complete response letter fromthe FDA.
There's something to do withthe manufacturing of the product
.
We do know that it's a dailyself-injection Patients need to
reconstitute a dry powder andself-inject.
There's not a lot more detailthat's been disclosed by Gilead
(24:24):
and we also don't know exactlywhat the timing is for or
whether they will resubmit toaddress the Complete Response
Letter in the U.
S.
In Europe it is being used.
I mean, it's a drug that'sdefinitely in advance on current
standard of care.
But when you think about it,bulevirtide achieves about a 12%
(24:48):
complete viral suppression, orwhat we call target not detected
no detection of the virus atall at 48 weeks, which is an
advance over zero, which is whatpatients were facing before.
With our regimen of tobevibartand elebsiran, the combination
regimen, we believe we can treatthe majority of patients and
(25:10):
get them to target not detectedor complete viral suppression.
Ben Comer (25:16):
And Alnylam is a partner on your hepatitis delta
and hepatitis B clinicalprograms.
What can you say about how thatpartnership came about?
Mark Eisner, MD (25:27):
Yeah, I mean Alnylam discovered elebsiran,
which is the siRNA component ofour regimen, so in that sense
it's very important.
I think it speaks to theimportance of partnerships in
finding external innovation.
Another example is the Amunix /Sanofi external innovation that
(25:48):
we brought in and just I thinkhow important partnering is for
biopharma generally, but Virspecifically, and we're very
excited to have elebsiran aspart of our regimen for
hepatitis delta and hepatitis B.
Ben Comer (26:04):
Is there anything else?
I know you have a partnershipwith GSK and respiratory disease
.
Is there anything else youwould say, Mark, about Vir's
more broadly I guess approach topartnering in terms of, you
know, partner selection andtiming.
Mark Eisner, MD (26:20):
Yeah, so absolutely.
I mean, I think it's maybe alittle bit under-recognized in
the biopharma industry or maybein the general public about how
critical partnering is, both tobring in external innovation,
and part of a competitiveadvantage we have at Vir is, I
think we are able to see whatgreat scientific innovation
(26:40):
looks like, and that would bethe example would be the TCE
platform that we brought in butalso to work with a partner like
GSK, where you know, Vir wasable to discover and bring this
sotrovimab to patients in 15months, but then to have a
partner like GSK, with a globalfootprint, with the expertise in
(27:01):
infectious and respiratorydisease marketing, and to work
together to get this drug to thepatients during a pandemic and,
just, you know, treat and save,you know, many, many, many
lives.
I think that was, you know, atestimony to how well Vir was
able to identify and work with abig pharma partner like GSK.
Ben Comer (27:23):
Yeah, and we talked about Vir's new focus, which is
infectious disease as well asoncology.
So I'd like to ask now aboutthe oncology indications that
you're pursuing and what kindsof milestones that you're
currently working toward inoncology.
Mark Eisner, MD (27:41):
Sure.
So I think maybe it's helpfulto start with what is the
problem statement?
So the problem statement forunmasked T-cell engagers, which
are approved for various targetsin the liquid tumor hematology
space, but for solid tumorsthey've just been too toxic.
Like unmasked HER2 orPSMA-directed T-cell engagers
(28:04):
have caused cytokine releasesyndrome where patients develop
respiratory compromise,hypotension, shock and, you know
, haven't been viabletherapeutics for solid tumors
because of the toxicity.
So the technology of themasking, with the PRO-XTEN
platform, which allows us tohave molecules that are masked
(28:30):
in the normal tissue in theblood, so pretty much inactive,
but when they get into the tumor, microenvironment proteases in
the tumor microenvironmentcleave off the masks and
activate the molecules, allowingthem to form an immune synapse
between the T cell and the tumorcell and kill the tumor cell
(28:51):
very effectively.
So that's, I think,fundamentally what's exciting
about the masking technology andhow it can improve therapeutic
index.
So we have three clinical stageprograms.
One is the 5818 program Sorry,yeah, 5818 program which is the
HER2-directed T-cell engagerwhich is potentially applicable
(29:16):
to a variety of HER2-positivetumors, including colorectal
cancer, where we presented someexciting data at a well and
we're doing a basket trial,phase one dose escalation trial,
where we are testing it out indifferent tumor types.
(29:38):
The 5500 program is directed atPSMA, which is an important
target for prostate cancer.
So we're currently testing thisin metastatic,
castration-resistant prostatecancer and we're escalating the
dose there, both in Q weekly andQ3 weekly scenarios, because we
(30:04):
want to get to a point where wecan potentially treat those
patients with metastaticprostate cancer.
And then the last one is ourTCE targeting EGFR, which is a
very, very broad antigen inmultiple tumor types, including
non-small cell lung cancer, headand neck cancer, and we are
(30:26):
planning to start phase onetrials in the first half of this
year.
Ben Comer (30:32):
Excellent.
I wanted to ask a questionabout the HER2 target.
I was speaking with the CEO ofa smaller biotech that's working
in oncology and a point that hemade to me was that the
fundamental problem in cancer istherapies being able to attack
(30:53):
cancer cells but not attackhealthy cells.
And this company is working ona kind of logic gating
technology that will, you know,essentially include multiple
receptors turned on and off,according to you know, sensing a
healthy cell versus a cancercell.
And the point that he made tome was that a target like HER2
(31:15):
is becoming increasingly crowded, people throwing a lot of
different modalities at it,because it's a target where, in
a sense, I guess, maybe yourtherapy can kill somewhat
indiscriminately.
Now, what you're saying with themasking technology adds some
nuance to that.
But I wonder, you know, is that, you know thinking about, you
(31:39):
know, the next big big leap incancer therapeutics?
Is it, you know, being able tokill cancer cells, kill cancer
without the resulting toxicities?
Do you see that as the currentlimitation?
Or would you give anotherexplanation for, you know, for
what's needed, I guess, for thenext big cancer breakthrough?
Mark Eisner, MD (32:02):
Yeah, I think that's an excellent question and
I do think that the specificityis super important here and the
masking in particular whichallows this mass T-cell engager
approach to work, because itallows us to dose escalate to
(32:22):
doses that can start to beeffective in killing the tumor.
So in HER2, it can bind theHER2 positive tumor cell and the
T cell and promote the T cellkilling of the HER2 positive
tumor cell.
Normal tissues like heart andlung tissues can express HER2.
So, to your point, we don'twant to activate the T cell
(32:45):
engager in normal lung tissue,normal heart tissue at all,
because that just bringstoxicity.
So I think what we've been ableto show so far in our public
data disclosures is that we candose these mast molecules, these
mast T-cell engagers, highenough to start killing tumors
(33:06):
while maintaining an adequatesafety, so only sort of minimal
cytokine release syndrome.
For example, one of the patientswe presented was a woman who
had very advanced breast cancerthat was infiltrating her skin
and she had been treated withnine prior lines of treatment
including Enhertu, which is arecently approved HER2-directed
(33:28):
treatment, Then you canliterally see visually this
tumor just clear from her skinwith 5818 over a 5 to 10-week
period.
it unequivocally had clinicalactivity in this patient who had
been through multiple, multipleother options.
(33:48):
And so I think it's case andback to our earlier discussion
around individual patients.
I mean we obviously need todemonstrate the effects, that
these are safe and effective inpopulations of patients, but
sometimes it's a patient likethat that really informs us that
we're on the right track with atreatment right.
And you know we have otherpatients as well.
(34:09):
There's a colorectal patientwho got this treatment right and
you know we have other patientsas well.
There's a colorectal patientwho got this treatment who's
been on drug for more than 18months and has been very, very
stable, and another prostatecancer patient on the 5500
program where you know they'vehad a very sustained suppression
of their PSA, you knowresolution of bony lesions on
(34:29):
MRI.
And it's patients like thatthat really tell us that we're
on the right course and I thinkalso for the teams it's just
really inspiring to see thosepatients kind of get back to
more normal lives and it justmakes us want to keep working on
this and advance the programs.
Ben Comer (34:49):
Looking forward into the future.
Now Vir has completed thispivot.
You're focused on oncology,you're focused on hepatitis B,
hepatitis delta.
What, I guess, are your topgoals for 2025 and maybe 2026?
And if you, would you know,what do you see as the biggest
(35:10):
challenge?
Mark Eisner, MD (35:11):
Sure.
So I mean 2025 for us is a veryimportant year for execution.
I mean, on the hepatitis deltaprogram, we are starting three
pivotal trials and we're goingto be enrolling our first
patient in the first half ofthis year.
So that's a laser focus for usand the team is getting those
(35:34):
trials up and running.
On the T cell engager side,it's continued dose escalation
for the HER2 and PSMA programsand getting the EGFR program
into the clinic, continuing toshow what efficacy we can get
with acceptable safety, minimalCRS and other acceptable safety
(35:57):
profiles.
So it's around really executingon those programs.
I think also on the researchside, it's using the antibody
discovery platform with dAIsYand the masked PRO-EXTEN
platform to work on the nextgeneration of tumor targets and
to work on, you know, in theresearch discovery space.
(36:17):
You know what's going to comenext, you know, besides the
clinical stage assets that wecurrently have.
And then the last thing I wouldmention is we are, you know,
going to have functional curedata for hepatitis B, a March
phase two study coming inquarter two of this year, and so
(36:38):
we're really excited about that.
The data at the end oftreatment were really exciting,
and what we have said is we'relooking for a partner to advance
that one into furtherdevelopment, because it's a
large program, it's going torequire a lot of resources and
that's a place where I think astrategic partner to develop
that globally will really reallybe important for us to find.
Ben Comer (37:02):
Yeah, and that raises a new question for me, which is
when do you get started on theglobal development efforts?
Do you, you know, is it afterthis next kind of phase readout,
and then you decide, yes, we'regoing for you know, we're going
to look for a partner, we'regoing to begin development
efforts elsewhere.
Maybe you're already in, youknow multi center locations
(37:25):
around the world.
I'm not sure, but can you giveme a sense of your kind of
global ambitions for thatproduct, given you know that
it's a really large indication?
Mark Eisner, MD (37:53):
Sure, so yes, so we certainly have started
planning of what the next phaseof clinical development would
look like the trial designs withthe next regulatory
interactions that we would have,and we've started thinking
about and talking to prospectivepartners.
I think this will be a processover time where our aspiration
if the data can support thecontinued development of the
functional cure point, which is,of course, fundamental we need
that would be to find a partnerwho would then work through that
with us and then ultimatelytake over that phase of
(38:14):
development for B, while wefully own and develop the
hepatitis delta trials ourselves.
Ben Comer (38:23):
Got it All right.
That is Dr Mark Eisner,executive vice president and
chief medical officer at VeerBiotechnology.
I'm Ben Comer and you've justlistened to the Business of
Biotech.
Find us and subscribe.
Anywhere you listen to podcasts, and be sure to check out the
new weekly videocasts of theseconversations every Monday under
the Business of Biotech tab atlifescienceleader.
(38:45):
com.
We'll see you next week andthank you for listening.
(39:06):
Enable breakthroughs inmedicine, healthcare and
technology.
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