Pratica di Shadowing: Biotech Story Time With Tal Zaks, M.D. (Part 1) - Impara a parlare inglese con i video
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you know arrows i was uh i was thinking before i came into the studio today
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that i should have i was thinking i should have made
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a large bag of popcorn for today's episode do you know
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why why do you remember the last time we talked with tall tall zacks uh it's been a while
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but i remember being wrapped wrapped entertained uh the stories were
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uh just titillating right like i was on the edge of my seat uh sometimes in disbelief
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and i thought this is a popcorn worthy episode alas i
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did not bring any popcorn to my chagrin i'm sorry next
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time bad planning a lot of people know him as the
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guy who was chief medical officer at moderna before during
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and after the company became a household name thanks to its mRNA -based answer to COVID.
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But even without that gold star next to his name, Dr. Tal Zaks has built a fascinating career as a physician scientist,
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an investor, a board member, and a biotech builder.
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Today, he's CEO and chair of the board of directors at Exilio Therapeutics, a non -executive director at five companies, I think, including Teva Pharmaceuticals,
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a private equity partner at Orbimed, and probably holds a few more titles
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that i'm missing storyteller he's a he's a not
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that we're setting the bar too high for right now
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but he is a prolific storyteller dr seuss over here i'm matt pillar
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and i'm anna rose welch
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and on today's episode of the business of biotech it's story time with fall
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so stay tuned
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because the stories tall tells are not tall tells although i
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guess they would be tall tells just not in the way
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you think i meant it that's a new level you didn't see
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that coming and
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that really hit me over the head like a shovel his
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stories are packed with biotech business building insights gained over a
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career spent uh spanning leadership roles at gsk sanofi teva moderna orbamed
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and now exilio therapeutics
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and probably like i said a whole lot more tall welcome
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to the show it's a real pleasure to be here we are absolutely thrilled to have you
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and as i said i i'm I'm sorry if we set the bar too high, but the last time we chatted, Hannah Rose and I came away thinking like this guy has got
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so many great anecdotes that not only like not only great stories, but like a lot of meat in them.
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Right.
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A lot of meat for biotech builders.
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So we're really looking forward to the conversation today.
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We have a ton to get through.
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I don't know if we'll do it all in one one episode.
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We might have to revisit with a part two.
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But before we get into the Exilio story, I want to get to know you a little bit and intro you to the audience.
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And so and I'm going to go way back.
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We're going to rewind the clock quite a ways.
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You immigrated to the U .S from Israel to do your postdoc at the National Cancer Institute
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and presumably at the time practice medicine.
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I mean, you're you know, you you practice medicine back then.
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Well, when you when you made that move, was it was that your sole intention career wise to come over here and practice?
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uh to be fair back in the day i just had
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an opportunity to come to the mecca of scientific research now
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i trained in the early days as a physician scientist an
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md phd it wasn't really a track i sort of built it
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because i got interested in an area of medicine uh that's called tumor immunology back then it wasn't the thing
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that it has become since but i was super curious
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and i had a wonderful opportunity to come to the lab of dr steve rosenberg at the national cancer institute
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and you know as an immigrant coming from across to the mecca of the nih
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you don't really think what's going to happen next you just say boy i'm at a place
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that has really redefined our understanding of immuno -oncology benefits for patients with cancer
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and the sky's the limit
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and i have to tell you i am to this day a very proud immigrant to this country and really
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if anything have been fortunate to take advantage of an ecosystem
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where truly the sky's the limit in terms of what we can achieve for uh for patients for ourselves for mankind
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so i in all honestly i knew i was a physician i had some interest in science
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and i just wanted to explore it yeah you just went and
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that ecosystem has opened up a lot of doors you know
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on in the periphery in front of you maybe in some cases behind you
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and you've taken you've seemingly taken advantage of every door that's
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presented itself well to be fair uh i have to say
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the first three years were actually marked by a lot of failure uh
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and in fact after three years there i you know, try to get a cancer vaccine to work.
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I actually proved why it didn't work.
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I tried to understand immuno -oncology.
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We had a theory as to what could be what what are today called checkpoints.
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We actually debunked it and it wasn't that.
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And after kind of three years, I said, oh, you know.
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I better go back and finish my clinical training.
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Yeah.
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And and it taught me the value of scientific depth.
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But I can tell you years later, when I came upon a saying by the late Nelson Mandela, it's become my favorite quote of all time.
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And he said, in life, I've either succeeded or I've learned.
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To be fair, in those early days, I had a lot of learnings.
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Still do to this day.
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Yeah, it's a it's I mean, it's a common refrain, but it's it's it's like there's a dichotomy.
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It's like there's a it's a common refrain, but it's all too often forgotten in this in this industry.
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Right well and i think you know we tend to just package it as well
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that was a failure instead of a learning right it's really just a terminology change
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but you know reframing that reframing it after you i do think i do think
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that when things don't go as expected that's actually when you grow
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and when you learn the most in fact in a roundabout way um
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and we'll come back to this later one of the fascinating
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things for me to reflect on covid was here's something
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that succeeded beyond my wildest expectations so you know what did i learn from
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that because there are learnings from that success
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but it's actually uh you know maybe counterintuitively it's easier to
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learn from failures than it is it is from successes yeah uh sticking back in
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that in that time frame after you completed your residency at temple
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and your fellowship at penn you joined gsk to work in clinical development translational medicine
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so tell us tell us why you made that transition to industry
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i have to say
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that was a completely non -obvious move to me at the
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time um i had spent many years in training in academia
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you know an internship another internship a residency a postdoc a fellowship
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and uh uh in in as i was finishing my fellowship
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i i actually uh won an asco young investigator award this
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thing handed out to fellows you've got a little bit of research budget
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and and and i came home really proud my son who was 12 looks up at me
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and says dad what's what's all the commotion about i was clearly excited
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and i look at him
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and said well you know i just i just won this young uh investigator award
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and the kid looks up at me
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and says dad what do you mean young investigator award like how old are you
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and i look at the kid
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and he had a point uh you know i was in my 38 39
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and and he's 12 and heading up to college in a few years
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and and here i am having fun training learning seeing patients
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but it really kind of brought it home
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that okay maybe it's time to actually go do something in the world and
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while I trained myself thinking I was going to be an
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academic physician I started my life actually as a pediatric intensive care unit nurse
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and I worked as a nurse on that side of the patient's bed
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if you will as I was training to be physician
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and i always appreciated teamwork
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and you know the academic uh world is driven by the axiom
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that there can only be one first author a few years before
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that i interviewed at a very prestigious institution and for fellowship
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and they said great yeah we'll have you as a fellow
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and with a little bit of chutzpah i asked them well you know
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if i come here as a fellow how quickly can i be faculty
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and they said oh okay let's let's think about
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that they took it up the flagpole
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and down came the answer it said look we we looked
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at your uh resume yeah you did a postdoc at the nih you had some papers great
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but you actually had more second authorships than first authorship
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so we're not really sure about you
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and i have to tell you i like i really took
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that to heart because i was actually more proud of the second authorships because
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when you're a second authorship it means you got to be
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part of something somebody else did the work you got to play a role in enjoying it leading
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and thinking through it uh while you were doing other stuff as well uh
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and so when the time came to sort of make the career move the the notion
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that uh i could actually go do it in a more team -based environment where really the purpose was getting better drugs.
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I just found that appealing.
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And, you know, if you take a medicine and you open it up, you know, whether it's tabs or a vial,
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you'll see there's a piece of paper rolled up in that that most people throw away.
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Well, if you open up that paper, it's actually the label.
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It's what the FDA says you should use it.
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And if you look at where, you know, who signed off on that label, where do these drugs come from?
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Well, they don't come from the university and they don't come from the National Institutes of Health.
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They actually come from drug companies.
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And so if you, as your mission in life, want to actually do better, especially in oncology with the state of affair of drugs,
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while we have very good drugs, we should and could do better and you want to be part of that doing better, then you go to where the action is.
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You go to where these medicines are made to have an impact.
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And that's sort of what propelled me to, despite having trained for so long, to be an academic physician, to actually shift gears and try it out in industry.
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Speaking of being in the place that makes the medicines, you continue to play your hand at a place that makes a lot of medicines in Teva.
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You've been there since 2021 as a board member.
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It's one of the world's largest generics companies.
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Tell us about that experience and how it's informed your take on the market.
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I have to tell you, I'm super proud of that.
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And I'm proud at a very deep level,
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because what Teva does is a reflection of the breadth of contribution to our industry that's often lost
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when we think of purely innovative companies.
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The innovation at the heart of the ecosystem is protected by intellectual property.
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And that is the engine that's allowed us to be
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so productive in the U .S in the last 50 years as the leaders of the world of therapeutic benefit.
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But the beauty is that that
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that contract with society actually plays out in the long run once the intellectual property expires and you now have generic medicines.
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And, you know, the stem pill I take every morning
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and the fact that my late father managed to live for 40 years with chronic heart disease and, you know, taking five, six, seven different meds.
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Those were all generics or most of them were.
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And by now, all of them are.
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Right.
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Right.
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And so the benefit of the previous era is now available to society at a fraction of the cost.
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Thanks to that.
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And in the discussion that we have about, you know, cost of drugs and intellectual property and all the other stuff,
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we often forget that there's a very long tail of benefit
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that we just keep raising the bar
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and then the price goes down years later for everybody to enjoy
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and that's worldwide and
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so i take tremendous pride in teva's contribution both on the
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innovative side we are an innovative company we we do develop innovative medicines
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but also on the generic underpinning of that
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that provides drugs for hundreds of millions of people every day freeze up right it frees up cost right
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and money to be able to cover the innovative stuff right the the breaking, the breaking new drugs on the market that, that aren't as cheap as generics, right.
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Or as, as biosimilars.
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So it's really, it pays into that innovation in its own way.
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Yeah.
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It's good illustration of, uh, Dr. Zacks is, uh, I guess, um, the breadth of his portfolio, right?
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Like the things, I mean, we're going to talk about Axelio here pretty, pretty soon, uh, doing some pretty novel and exciting things.
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And he did obviously some pretty novel and exciting things uh beginning in 2015
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when he took on the stint as cmo at moderna
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so we could spend like i don't want to do this
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i don't want to do this i want to get i want to give this its fair share
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but we could spend a couple episodes talking about stories from
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yes those moderna days of moderna age you know like not
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to not to put too fine a point on it but you joined moderna in 2015
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like just let that sink in for a minute what tell us about that like you you start like was this
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was this a right place right time kind of situation was
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it like you you saw something coming like what's what's the
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story there how are you reading the tea leaves what's going on oh i wish i could be
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that smart uh you know uh i i was listening to
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a podcast a few uh weeks ago general petreus uh made
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a comment he referenced uh the late uh long late roman philosopher Seneca who said that luck is when preparation meets opportunity.
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So in a way, I was prepared.
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I had spent a significant chunk of my life by then in oncology drug development.
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As you mentioned, I started GSK, ended up running Santa Fe's global oncology team.
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And at that point, I had sort of the opportunity to kind of look around at the biotech system and figure out,
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well, what's new that's coming and what are some interesting ways to fill our pipeline
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and up until that point i was a medical oncologist through
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and through i cared about better medicines for cancer patients i
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didn't care about where they were coming from the proof point
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i actually spent a couple years at cephalon cephalon had developed
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two of the oldest poisons known to man as a very effective cancer chemotherapies.
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One is arsenic trioxide, which cures a subset of leukemia.
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So Fine by me, right?
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The clinical benefit is what speaks to me.
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But as you're a scientist and you get sort of curious about where's innovation coming from,
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I had the opportunity to look within the Boston ecosystem at a whole bunch of stuff.
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And I came upon Moderna and the idea of mRNA.
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And it made me stop and sort of think differently about translating science into medicine
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so by then i sort of realized that i was my happy place
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if you will is is between the science
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and the medicine not pure science for the sake of science not just pure medical practice even though i did
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that a number of years as a volunteer at the philadelphia va
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but it's actually that in between and moderna was had an emerging interesting idea
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and platform that was very orthogonal to my thinking.
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It was not, hey, we have a cancer patient and cancer here as a need.
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Can you make a medicine?
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It was we have this innovative idea of a new platform.
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And if we can translate it into medicine, what would those medicines be?
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And that's a very different way of asking the question.
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Now, in full transparency in 2015, all the data we had were just an animal model in mice uh
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and most people thought this thing was never going to work uh i have been fortunate in life that in
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that uh my wife who's the smart one in the equation
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actually has a phd in biochemistry you know she looks at me
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and says well you know it's all mrna it's high risk
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but hey if this speaks to you go for it
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and i was in a place in life where uh it was time to take risk
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you know and the way to think about it um i had a big birthday
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that year and one of the things that happens
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when you reach a certain age is
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that you stop looking at the next career thing you're going
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to do you start looking at time in reverse you said okay
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and the time
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that left to me in this world what do i want to get done what do i want to accomplish
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and and then you realize you'd rather
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fail or learn trying to address a big question than just do something small and incremental
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uh this was a big question this was a question
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that most people thought was not going to work uh i
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mean i can show you nature papers back in the day uh referencing moderna
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and theranos in the same sentence for crying out loud um
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and and it was a very different way to kind of challenge yourself to go make medicine
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so i i signed on because i thought that if this would work
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we should be able to go from an idea on a
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whiteboard to a medicine being studied in man at a fraction of the time
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and the cost of what traditional drug development takes.
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And it had such potential in terms of a platform that could lend itself to once you do the first one,
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the other ones should actually work that repeatability that is unheard of in traditional pharma.
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And in fact, we'd actually proven it.
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One of the things the public is not aware of is that, you know, the COVID vaccine was not Moderna's first vaccine.
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It was actually the ninth virus against which we tried to raise neutralizing antibodies in humans.
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And our success rate for the prior eight had been eight out of eight.
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So COVID for us inside was was not a surprise, actually, that it worked.
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There were a lot of other things surprising about it.
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But we knew this platform could actually get there.
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In fact, for years, we have been working with an urgency to get there in time.
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So I really like this point.
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You know, when you joined Moderna, I think the instinct there was to really be part of a foundation, right?
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You wanted to build the foundation for mRNA medicines.
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And instead of making sort of incremental advancements, really tried to develop this proof point for mRNA as an actual therapeutic, as a vaccine candidate it
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but i'm really i'm curious to to learn more about you
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know your priorities as a cmo stepping into a company at this time
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when mrna was again as you said compared to theranos right
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like it wasn't a household name a lot of people were hesitant to believe
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that it would work it was high risk you know what were your priorities as a cmo
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when you stepped into this into this company and
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and in these early days what did that what did
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that look like
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and entail i think uh a lot of moderna's success stems from two factors the first is the courage that those
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that came there before me um stefan boncel steven hoog uh to ask the question don't you know suspend disbelief
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if it works what can you do of it?
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And then the very thoughtful risk mitigation approach to try
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and take several shots on goal in different dimensions to try to work yourself across different things that could work, but you don't know that they could.
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In those days, they spanned infectious disease these vaccines, they spanned.
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uh oncology efforts they spanned rare disease uh one of the things
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that i personally started uh shortly after joining was the personalized cancer vaccine uh
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and you know we can come back to that uh you know
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if you want a cliffhanger into this episode we can talk about cancer vaccines
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because it's a fascinating story in fact it's much more fascinating to me scientifically than than even covid
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but when i joined uh and and this is where your popcorn will will find a place
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when i joined in march of 2015 uh stefan von selva
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ceo asked me to give uh an all -employee town hall uh three months into my tenure
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so in june of 2015
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and he wanted me to explain to the employees there were
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about 300 people at modern at the time why was it
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that a unicorn on paper company in boston uh
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so secretive is actually the first clinical trial is going to
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be a vaccine against the pandemic flu threat out of china
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that was our first phase one we started at the end of 2015. and
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so what we did back in those days is we used
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to rent the the auditorium next door uh it was actually
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a movie theater the kenthal square theater um we used to
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rent it out for random thursday afternoon we'd give all the employees free popcorn they'd sit
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when the executives would get on stage and
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and you know tell the story of what the company was up to in the last couple months
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and so it's my turn june of 2015
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and i told us to fund great we're in a movie
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theater i'm going to take some license with my presentation i'm
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not going to use your usual slide template i'm going to make believe we're in a movie and
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so i get up everybody's with popcorn i'm the new cmo
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said guys pretend this is a movie the the theater goes dark
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and on the screen comes a slide
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and the title of the movie is how moderna will save
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the world june of 2015 the next slide is a pg -13 green rated thing right to get everybody
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and then the rest of the presentation
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started with the spanish flu in 1918 goes through the fact
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that still back then in 2015 we don't have a good
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vaccine response we don't have good antivirals all we have is
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these masks these picture of people walking around in masks
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and i flashed those pictures up in june of 2015
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and basically the gist of the talk was our platform it's
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clear the low -hanging fruit is going to be vaccines for a whole host of technical reasons
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and we owe it to ourselves to the company to society to make sure
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that we're advancing these vaccines both those that are of perceived commercial value
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and those that could be of public benefit
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and in fact that's what we proceeded to do we had advanced a few candidates
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that have commercial background i mean cmv right now uh is already in in phase three there uh
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but in parallel we worked on flu we worked on zika in 2017 that's
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when part of the u .s government got to go and
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and we built this track record of the ability of this platform to actually execute towards a pandemic need uh
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and i'll tell you it came full circle In September of 2019,
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Stefan and I went down for our sort of annual meeting with the NH folks, who was there at the time,
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and they came to know us through the Zika pandemic in 2017, and we started to collaborate.
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And by then, we had shown
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that the mRNA vaccine could actually work to protect an animal model of a cousin of COVID called MERS.
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uh and i we were telling uh the team there about the most recent data we had
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and i remember at some point dr fauci kind of stops me
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and says so are you telling me this is the best vaccine platform i've ever seen uh -huh
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and you know me being me i basically looked at the same dr fauci yes
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and let me explain why and and and so the upshot of
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that meeting was actually that Moderna and the NIH were going to form a collaboration to pick a virus,
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something nobody ever heard of.
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We'll just send you the sequence.
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You guys can start the clock, see how fast you can make a first batch, and we'll run the phase one clinical trial.
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And in November, the NIH, November of 2019,
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Dr. Fauci actually published a paper talking about pandemic preparedness of various platforms
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and mentions mrna there as the leading platform ready to serve in a pandemic whether it's influenza
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or a related respiratory virus
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and as we were talking to the nh trying to figure out what would be
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that test case somebody started coughing into wuhan
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and the rest is oh my gosh uh you realize how
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much fodder you're you're providing for conspiracy theorists right now dr
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zacks i mean really takes time to a whole new level where's my popcorn i know
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but i'm curious so i i i can tell you just to finish the note
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because i i have to say uh you know I got to know all sorts of conspiracy theorists back in 2020.
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One of my, I think, learnings from the whole era was how critical it is
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that we build public trust and understanding and what it is we do.
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If if if we do everything we do in translating science into medicine, but the public doesn't trust it, then it will have been for not.
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And I spent a lot of energy as the chief medical officer back in those days.
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And I still believe it's part of each and every one of our ethical obligation to be out there,
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to tell the story, to explain to people where does this stuff come from?
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This is not black voodoo.
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This is not some magic mystery.
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This is people hard at work trying to understand the science and trying to translate that science.
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And we did we did a couple of things that were I'm really proud of back in that era.
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The first was in as the phase three trial was going on.
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I remember being on a on a on a webinar with the National Academy of Sciences of New York State, and they asked me, OK, at the end of it, there was a Q &A.
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And they said, Dr. Zax, what are you worried about?
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And and they expected me to say, oh, I don't know if it's going to work this.
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Then the other said, look, I'm not worried about safety.
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I'm not worried about efficacy.
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The one thing that keeps me up at night is that our trial enrolls people of diverse enough
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representation of the great country of ours so that when the data comes out, people can relate to the veracity of those data and can see themselves in the trial.
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And I think Moderna went on to really pioneer enrollment of diverse populations in phase three and in all subsequent trials,
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partnering with both national and regional sort of experts
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and leaders of the community to make sure that clinical research is both accessible to everybody and representative of everybody.
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And the other interesting thing was, again, as I was thinking, how do we relay this message to the public?
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I actually convened a small ethics panel for the executive team at Moderna.
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You're not going to find this on any website.
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This was not done for external consumption.
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This was really to get external advice of people like Art Kaplan
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and other experts in ethics on how should we be thinking about our protocol.
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And one of the experts there, a friend of mine, Ann Beal, Ann is a wonderful black pediatrician from New York City.
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She was the first chief patient safety or chief patient officer at Santa Fe.
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She's today on the board of GSK.
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And I brought Ann in and Ann looks at me and says, Tal, I've been in your shoes.
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The only way you can do this is to be transparent to the point of discomfort
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and i listened and i said that's going to be the motto of our medical affairs organization
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and in the ensuing weeks we had a lot of internal
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conversation i was pushing to have the phase three protocol of the covet vaccine actually published
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and companies don't usually publish protocols uh on the web certainly not unredacted
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and certainly not as the trial is still ongoing
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and we finally prevailed and in september we we we went out uh
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and we put the entire protocol on the web
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and i'm very happy to say
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that all the pharma followed some of them within hours we
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got one of the most favorable articles ever written on pharma on the new york times in september of 2020
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but more importantly journalists who used to call me up in those days
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and say hey you know what are you not telling me
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how many patients are you going to sea etc suddenly the
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conversation was tall on page 87 paragraph two of your protocol
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can you explain to me how the power of the statistics work right
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so you could actually take now the conversation with the public
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and i you know i have tremendous respect for to journalists
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because at the end of the day you're the ones who
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translate this to do what the public actually gets to listen and and figure out.
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And so it changed the dialogue that we had with the public on what that protocol was actually trying to do.
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He says one of the most favorable articles on pharma, the New York Times is, I'm thinking like a favorable article on pharma is a win,
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and it doesn't have to be one of the most, right?
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I mean, if it's...
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Penny one is a win.
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If it's 52 % favorable, that's a win.
411
No, I really, you know, so I think you kind of answered this, this question that I have.
412
But so, you know, you built this foundation, you weren't concerned necessarily about mRNA being efficacious and safe.
413
The big priority for you as the pandemic started to hit in the in the year after, right, as you released your vaccine was really making sure
414
that you were telling the full story and that everyone who needed to
415
and wanted to see that data could actually access it and be able to able to understand that story, you know.
416
Was that perhaps the biggest part of your leadership at
417
that time as a CMO in an MRNA company once it kind of became a public good, right, a publicly known household name?
418
Or how did you see your priorities sort of shifting as MRNA suddenly became an actual medicine
419
that was commercialized and you had to continue moving forward and being a CMO of this company?
420
Yeah, I think that's true.
421
So if you if I look back at 2020 and now, you know, with the wisdom of insight, it really is there's two parts to that year.
422
And the first part, when we sort of had to muster up
423
and figure out how to get this done
424
and how to do it in a way that would avoid all the obvious pitfalls.
425
And by the way, how to do it while learning to work in a completely novel manner.
426
That was all consuming.
427
I mean, if you would have told me in 2019
428
that I'd be developing a vaccine in 2020 and I'd be doing it with a team of dozens of people,
429
all of whom I had hired through Zoom and never met.
430
And I would be doing it with three government agencies who had to align on protocols and endpoints,
431
none of whom got in the room together with each other, let alone me um
432
and i do it in record time such
433
that we went from an idea on a whiteboard to an
434
authorized vaccine in 11 months i would have thought yeah that's that's that's impossible
435
and yet and yet we did it and
436
so that's where you kind of there's learnings from that success in terms of how we work
437
across uh individuals and what can work with remote working
438
and zoom and what actually takes people to get in the room together to align on things
439
and and i think we as a society are still learning that lesson
440
but it's clearly i think for us the development of the vaccine was probably a unique edge case
441
that everybody else experienced in terms of what can you get done remotely
442
and how to go about building a an effective remote working
443
environment the second half of the year I think once the phase three was sort of rolling on its tracks,
444
and then I had to pay attention to two things.
445
I think one of them is, as you said, being the public face, making sure that I can tell the story, that I can represent Moderna.
446
We had very critical FDA meetings, advisory committee meetings cdc meetings etc the other one
447
that is a story that's not often told actually has to do with safety
448
and what people sort of don't realize is and probably this is
449
this is a good explanation for some of the conspiracy theorists out there
450
The mRNA vaccines are the most intensively studied from a safety perspective, medical intervention in the history of humanity.
451
We have dosed, I don't know, one, two billion people with these medicines.
452
We've done it with the most modern tools for data collection ever available to mankind.
453
We've done it with reporting through all forms of modern communication technology.
454
We've done it using the best tools available today of big data analyses for any kind of signal.
455
And the proof is that when you had very rare adverse events
456
that happen at a rate of 1 to 150 or 1 to 200 ,000 cases, those were picked up within months.
457
And that's what happened to the AstraZeneca vaccine, the J &J vaccine, if you recall back.
458
And even Moderna had this this very low signal of the myocarditis that had been picked up and then validated.
459
So there's I don't think there's anything significant about the safety of these vaccines that we don't know.
460
It just doesn't make any sense given the way we collected.
461
And I can tell you the amount of man hours, hundreds of millions that it actually cost to collect the safety data.
462
That is the iceberg under the water.
463
And to the degree that I was sort of steering the ship in those days, that was the thing that I had to pay careful attention to,
464
to make sure that we are actually collecting the data as required by regulations.
465
And by the way, global regulators around the world would have weekly teleconferences without me, FDA, the Europeans, et cetera, et cetera.
466
And they would be talking about the safety of our vaccines and what it is that they get direct reporting.
467
And when you think about it.
468
just to give you a numbers on it
469
when we started down this path we took a look at the previous vaccines launched
470
and we thought that we would get about three to four times the reporting of adverse events
471
that any other vaccine would happen that's what we geared up to
472
when it actually got rolled out we got about 15 folds i mean i don't remember the exact numbers
473
but it was over tenfold what we had expected
474
because of this heightened sense of vigilance because of the public scrutiny
475
and all rightly so and it was our job to react to
476
that collect the data sift through it and make sure
477
that we report it accurately and so that's a story that's not often told
478
but for me was critical so that i can be out there
479
and and and say yep you know
480
if you want to know what the side effects are you remember
481
that fda label go back and pull it up because if there's anything we saw by law, it's on there.
482
And we're having those conversations with the FDA to tell them about it.
483
Yeah.
484
You know, very few, it occurs to me, the very few, very few CXOs in a similar,
485
will ever find themselves in a similar position where that one moment, moment in time, you know,
486
really throws the afterburners of your career on, right?
487
Like very few people are going to see that and very
488
and fewer still fewer still people are going to survive it
489
come out the other end like you know hey the contributions
490
there being biotech yeah i i stand on it um
491
so you know it goes without saying that that
492
that had to have been a supreme confidence builder even even in your already very successful
493
and advanced career that had to be a supreme confidence builder
494
but and and as i said we could talk about covid for like the next three hours
495
but um i want to i want to kind of shift back to like what, what makes Dr. Talzak's, Talzak's who he is today and,
496
and kind of keeps him moving forward.
497
So taking sort of, sort of that specific experience off the table, what other inflection points during your, you know, CXO, you know,
498
VP, even research experiences with your previous companies have in a similar,
499
but maybe more muted, more muted to the public way influenced, uh, your confidence in, in your,
500
uh, career trajectory, you know, your decisions to go on and be a, be a board guy, be a founder, be a, you know, uh, the, the leader of Exilio, for instance, now.
501
Uh, it's a combination of factors, you know, it starts with the absolute joy.
502
of seeing clinical benefit come at the other end.
503
I'll tell you a story back when I was at Sanofi.
504
We had a drug that was in phase one, just the first phase of clinical research.
505
And it was, it targets something called CD38 for patients with a type of blood cancer called multiple myeloma.
506
And this phase one had been going on for very long because we started at very low doses.
507
We were going very, very slowly, and it wasn't clear that it was going to work, so people weren't excited to enroll.
508
And one day, the team comes back and tells me, you know, you remember that 70 -year -old patient that we had, and he'd just gotten a couple of doses?
509
Well, he decided to go off protocol, and he's no longer participating.
510
I'm like, why?
511
You know, we just lost the data point.
512
This is hard enough as it is.
513
And they say, well, you know, here's what happened.
514
We gave him two doses
515
or three doses of the drug he went into a complete
516
response he's 70 year old he's been feeling like crap for
517
the last decade of his life he finally got the opportunity to go to europe
518
and take the summer off and do that trip he's been dreaming up
519
so he decided he's not coming for his next dose he's going off to europe to live right
520
and then you go okay i guess i guess that's okay
521
that's what we strive for right improve quality of life exactly
522
so uh so so it's those stories that that you sort of
523
that you live for on the you know i i think i've been fortunate to to have mentors and colleagues
524
to be able to talk to and have have sort of steered me right whether it's people like steve Rosenberg,
525
who is still there at the NCI now 50 years as the towering modern giant father of immuno -oncology.
526
I mean, a lot of therapies we see today, the T -cell therapies all started in his lab back in the day.
527
I've been fortunate to have a supportive wife who understands what I do
528
And more than that will actually tell me to my face
529
when I'm talking nonsense and tell me the stuff I don't want to hear.
530
And I've been blessed with having colleagues, you know, one of the.
531
privileges that we have in the world in this ecosystem is
532
that the end game is something tangible
533
that is easy to be passionate about we're not making widgets
534
we're making people feel better live longer we're trying to cure diseases we're trying to prevent horrible illnesses it is easy to get
535
that as a rallying cry what's hard is then to figure
536
out okay with all the unknowns in biology along the way how do you do
537
that now in the i i think this in in this phase of my career
538
one of the things i learned at moderna sort of through
539
doing is the importance of aligning return on investment with uh with kind of innovation and doing good for patients
540
and it sounds trite but it's actually not obvious and it's not trivial to get right the
541
Our ecosystem has been so productive, but you have to understand the drivers of this ecosystem,
542
because if you look at other economic models of trying to translate innovation into health care benefits, they have not worked nearly as well.
543
And so I judge it by the results
544
and I am deeply respectful of the underlying economic ecosystem
545
that rewards innovation and rewards investment in high risk areas with a return on that investment.
546
you know i was um i was kindly invited to a recent uh summit
547
that uh one of the national academy of sciences medicine
548
and engineering had about how to better align uh investing in innovation
549
and therapeutics with unmet need and
550
and one of my points to them was i i'm not ashamed of saying return on investment
551
when we talk about drug pricing uh you know we we we often talk about
552
kind of reimbursement and reimbursement is a term that is fit for
553
when i go out and have a meal
554
and i need somebody to pay for the meal we don't
555
work for reimbursement let's be fair we work for a return
556
on the investment my shareholders my limited partners right now in
557
venture a lot of them are pension funds they give me
558
a pot of money seven years later i need to give them a bigger pot of money back
559
because they got to go pay those pensions that's what propels our system
560
that is commercial investment
561
and for me since i was fortunate to never actually do
562
anything strictly for money uh i became super curious to understand
563
and immerse myself in an ecosystem where
564
that part of the value is actually a very objective
565
and legitimate yardstick um you know sweat equity
566
and capital equity tend to be rewarded differently i've sort of lived now through both
567
and uh when
568
when investors at moderna used to ask me well you know
569
what's the stock price should i invest is it too high
570
is it too low what's it going to i used to look at them
571
and say look you can do what you want with your
572
money i'm actually investing something much more valuable than money at moderna
573
and that's my time on earth uh
574
so you be the judge of your money i think sweat equity
575
and capital equity are different
576
and these days i'm curious to immerse myself in this side of the business of biotech
577
if i may uh to understand what that return on investment looks like
578
and how do i best align it with the things
579
that i still inherently care about
580
which is translating science into medicine yeah yeah in the in
581
that vein i mean one of the first questions that investors ask,
582
one of the first questions that regulatory agencies ask when they're looking at investigational therapeutics is about unmet medical needs.
583
What does it address?
584
Lots of research in biotech builders thus go about their business searching for solutions to unmet medical needs.
585
Why not?
586
It potentially wins the favor of markets and agencies.
587
But you, on the other hand, And to have shared a somewhat, you know, at face value,
588
perhaps contrarian opinion that unmet medical need is not really what drives innovation in this industry.
589
So I guess I'd ask you for some explanation of that philosophy.
590
Explain yourself.
591
Yeah.
592
Well, you know, it struck me as I was starting out at GSK.
593
I remember at one point we said, okay, we're going to focus on lung cancer because it's an unmet need.
594
And being the flippant young guy that I was, I told the head of the division that actually if he wanted to have an impact on lung cancer, he didn't need to do much work.
595
GSK already had the best drug in their portfolio at the time.
596
And he goes, yeah, what is it?
597
He said, it's Nicorette.
598
unmet need hasn't changed.
599
And so we've had, you know, we've had cancer for eons.
600
And so it's not unmet need per se, that's driven all the new medicines we have.
601
So it's actually new understandings in science and technology that then that are driven primarily by curiosity.
602
You know, when Caitlin Carrico, whom I have a ton of respect for, started fiddling around with the structure of RNA to understand why, in some cases, was it killing cells
603
and what could she do to the chemistry to stop it from killing cells and get progene expressed.
604
She came upon a really interesting discovery, but nobody knew what to do with it.
605
In fact, the IP lay fallow for years.
606
They kind of licensed it to somebody else.
607
And it wasn't until people who actually said, huh, there's something that maybe we can get translated.
608
And even then, the first folks who picked that up, their idea of what to do with it was just following their curiosity.
609
Oh, can I reprogram the stem cell to go be something else?
610
Which is super interesting scientifically, but we still don't know how to make a medicine out of it.
611
And so for me, that bit of translation in the middle, pure innovation is opens up the potential.
612
That's the curiosity driven.
613
That's basic science.
614
That's basic technology.
615
When Bob Langer discovered that he could make lipid nanoparticles,
616
and Bob is a legendary MIT professor who's the father of the modern lipid nanoparticle and frankly, one of the fathers of the current ecosystem,
617
as we know it, of Boston Biotech.
618
And that's because of his deep understanding that when he discovered he could do something, and that something was everybody else thought he couldn't do it and shouldn't be possible,
619
that opened up a wonderful world of intellectual property.
620
And his understanding of the value of intellectual property
621
and the ability then to showcase what you could do with it to attract investment, that's what started the ball rolling.
622
And frankly, Moderna is sort of the culmination of the curiosity of people like Bob Langer,
623
like Caitlin Carrico, but actually putting it together in something that now is useful.
624
In fact, even in the early days of Moderna, we were exploring a whole bunch of different things and trying to make different types of therapies with it.
625
Moderna still is exploring the next frontier, whether it's cystic fibrosis or rare disease.
626
Now we know vaccines work and what happens is unmet need becomes the prism by
627
which you focus the light it's not the source of the light the source of the energy is actually
628
that scientific and technical innovation
629
and that's brilliant people who just are just super curious to go to go do something
630
or investigate something but the ability to then focus
631
that potential show through the prism of unmet need is what gets us medicine.
632
I think that's a really interesting distinction, especially given where we are right now,
633
I think with mRNA and you're positioning yourself right at the at the head of a brand new mRNA company, right? So,
634
you know, where there's still so much unknown unknowns right around the science of mRNA
635
and how it works and the delivery of it
636
and how it's going to perform in different cell types
637
and how we get it to express longer such there are
638
so many different scientific questions um
639
and we also you know tend to i think celebrate mra
640
at face value for the ability to manufacture more efficiently right
641
you've talked about this in comparison to other cell -based medicines right
642
so you know i'd be curious to get your sense on
643
the trajectory of innovation in this space what you really think is
644
are some of the the pieces here that are really driving further innovation in
645
that space right And that we are starting to funnel into unmet need to some extent to make these into therapies.
646
But what are those, you know, what's stoking the innovation in the mRNA space today that has you the most excited?
647
And what's at the root of that?
648
So I think the two current frontiers for mRNA medicines have to do still with the original questions in a way,
649
except we've moved the ball down the field.
650
The first is what cell can you get the mRNA into to mediate the protein translation
651
that would lead to a therapeutic benefit?
652
Vaccines were the low hanging fruit
653
because all you need is a needle in the arm and it goes to the local lymph nodes.
654
And all you need is a smidgen of protein produced and you mimic a viral infection and off you go.
655
The next place where you can put it is likely intravenous.
656
And I think that's also been proven.
657
And we've demonstrated, we at Moderna back in the day, shown that we can inject mRNA encoding just for an antibody intravenously
658
and it goes to the liver and it will make you antibody and you get therapeutic doses of antibody.
659
So can you get it to the lungs?
660
Can you get it to the bone marrow?
661
Can you get lupin nanoparticles into immune cells?
662
Can you get that into the brain?
663
I think that's some of the those are some of the frontier areas where people are trying to push the boundaries.
664
The next the other dimension is, well, what actually can you encode in the mRNA?
665
And initially, the place you start is the stuff that's best understood because you want to minimize risk.
666
And nothing is better understood than an antigen for a virus.
667
And, you know, it's no mistake
668
that all the COVID vaccines all use the exact same spike protein that everybody now knows what a spike protein is.
669
OK, that was easy.
670
But you could actually make proteins that are much more complicated.
671
You can make proteins that require several several subunits to come together
672
and you can make proteins that have not been seen in nature.
673
You can invent new proteins that have novel functions or improve on functions in very creative ways.
674
I am curious about that frontier personally, that's where Exilio comes in,
675
because for me, Exilio, this gene therapy company that I've now taken on,
676
is actually at the forefront.
677
It can combine innovation that comes from two different sources.
678
One of them is mRNA and a lipid nanoparticle as a drug format.
679
We can give it, it can go to cells where we understand can already go to, whether it's the liver or immune cells and it can translate protein
680
and you can actually give it repeatedly you can give it once twice three times in fact you know moderna
681
and their lead indications are have gone now for for about
682
a year in their first two diseases giving it every two to three weeks no problem
683
but the second thing is gene therapy can i actually integrate
684
a novel piece of genetic material in a safe way into the human genome to produce a therapeutic protein.
685
And then I don't have to keep treating that patient.
686
Well, that's as close to a cure as I know.
687
And so what this company
688
that I'm now running is trying to do is basically take
689
a page of evolution as a starting point of some elements that can actually do this in nature, but use modern tools of protein engineering to improve upon their utility
690
so that we can actually use mRNA
691
and a lipid nanoparticle as a way to bring gene therapy to the forefront
692
and do it not just by doing one or two small, you know, alterations of a genome,
693
but actually to insert an entire piece of missing genetic material and cure a kid with a genetic disease, for example.
694
And this, my friend, is where the cliffhanger comes in
695
because we do have a hard stop and
696
because my next series of questions we certainly cannot tackle in four minutes we cannot those questions those questions being
697
if curiosity is to be rewarded it it must be funded
698
who is funding curiosity who's willing to fund how do you
699
willing to fund these innovation come on in this market who's going to fun we're going to go down
700
that path we're going to get to know exilio uh in in detail
701
but we're not going to do it right now folks we're
702
going to do it in part two of this conversation
703
that i am um hereby committing dr tall zacks sorry you're
704
gonna have to come back to tell some more tall tales with pleasure colleagues
705
and we will have popcorn for that one we will have popcorn for that one.
706
I will bring the popcorn.
707
But for now, we are going to let you off the hook to meet your next commitment.
708
And I will be in touch with your people to get part two scheduled very, very quickly because I might get to run right on the heels of this one.
709
This has been a fascinating conversation and I appreciate your time.
710
Stay tuned.
711
I look forward to it.
712
Thank you so much.
713
Thank you.
714
Thank you.
715
So that's part one of Exilio Therapeutics, CEO and chair of the Board of directors, Dr. Tal Zaks.
716
I'm Matt Piller.
717
And I'm Anna Rose Welch.
718
You just listened to The Business of Biotech.
719
We're produced by Life Science Connect in support of a deep community of learning, solving, and sourcing solutions for biotech and life sciences leaders.
720
And if you haven't seen it yet, be sure to visit our video cast page under the listen and watch tab at bioprocessonline .com.
721
There you'll find this and hundreds of other videos of our interviews with biotech builders.
722
While you're there, subscribe to the Business of Biotech newsletter at bioprocessonline .com backslash B -O -B.
723
In the meantime, we'll see you next week, hopefully, for part two of Storytime with Tal.
724
And thanks for listening.
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Vocabolario e note di pronuncia per questa lezione
Questa lezione di conversazione si basa sul video “Biotech Story Time With Tal Zaks, M.D”. Questo video contiene 724 frasi e 9464 parole da ripetere con lo shadowing. Il parlato dura 55:08. Chi parla ha un ritmo naturale di circa 172 parole al minuto, vicino a una conversazione quotidiana. Il 82% delle parole rientra nelle 3.000 più comuni dell’inglese; conviene studiare le altre prima di iniziare.
Vocaboli chiave di questo video
15 parole del video che vale la pena imparare, con pronuncia e significato:
| Parola | Pronuncia | Significato |
|---|---|---|
| vaccine sostantivo | /vækˈsin/ | vaccino |
| innovation sostantivo | /ˌɪn.əˈveɪ.ʃən/ | innovazione |
| ecosystem sostantivo | /ˈikoʊˌsɪstəm/ | ecosistema |
| popcorn sostantivo | /ˈpɑp.kɔɹn/ | popcorn, mais scoppiato |
| curious aggettivo | /ˈkjʊɹ.i.əs/ | curioso, interessato |
| translate verbo | /tɹænzˈleɪt/ | tradurre |
| physician sostantivo | /fəˈzɪʃən/ | medico, dottore |
| innovative aggettivo | /ˈɪn.əˌveɪtɪv/ | innovativo |
| curiosity sostantivo | /ˌkjʊɹ.iˈɑ.sə.ti/ | curiosità |
| builder sostantivo | /ˈbɪl.dəɹ/ | costruttore, costruttrice |
| equity sostantivo | /ˈɛk.wɪ.ti/ | equità, parità |
| intellectual aggettivo | /ˌɪntəˈlɛkt͡ʃʊəl/ | intellettuale |
| dose sostantivo | /ˈdəʊ̯s/ | dose |
| therapeutic aggettivo | /ˌθɛɹ.əˈpjuː.tɪk/ | terapeutico |
| virus sostantivo | /ˈvaɪ.ɹəs/ | virus |
I phrasal verb che sentirai
| Parola | Pronuncia | Significato |
|---|---|---|
| figure out verbo | scoprire, rendersi conto | |
| open up verbo | aprire | |
| go back verbo | tornare | |
| look forward to verbo | non vedere l'ora | |
| pick up verbo | tirare su, sollevare | |
| come back verbo | tornare | |
| end up verbo | andare a finire, finire | |
| get through verbo | /ɡɛt ˈθɹu/ | superare, farcela |
Frasi da ripetere
Frasi brevi e complete del video che puoi riutilizzare nella conversazione di tutti i giorni:
- Can you make a medicine?
- Zax, what are you worried about?
- Can you get it to the bone marrow?
- Can you get lupin nanoparticles into immune cells?
- Can you get that into the brain?
La grammatica di questo video
Le strutture che chi parla usa di più, con le parole esatte del video:
| Struttura | Nel video |
|---|---|
| Present perfect continuous have/has been + -ing — un’azione iniziata prima e ancora in corso | have been working · he's been dreaming |
| “Used to” used to + verbo — un’abitudine o uno stato passato che non è più vero | used to call · used to look |
| Present perfect have/has + participio passato — un’azione passata che conta ancora adesso | it's been · has built · has become |
| Forma passiva be + participio passato — conta ciò che accade, non chi lo fa | being wrapped · were actually marked · is driven |
Pronuncia a cui fare attenzione
Chi parla usa 144 contrazioni e forme ridotte, come I'm, don't, we're. Pronunciale nella forma breve, così come le senti.
- I suoni “th”: therapeutic /ˌθɛɹ.əˈpjuː.tɪk/, theater /ˈθi(ə)tɚ/, ethics /ˈɛθ.ɪks/, theorist /ˈθiːəɹəst/, breadth /bɹɛdθ/
- I suoni “sh” e “zh”: innovation /ˌɪn.əˈveɪ.ʃən/, physician /fəˈzɪʃən/, fellowship /ˈfɛl.ə.ʃɪp/, explanation /ˌɛkspləˈneɪʃən/, translation /tɹænzˈleɪʃən/
- Parole lunghe — attenzione all’accento: innovation /ˌɪn.əˈveɪ.ʃən/, ecosystem /ˈikoʊˌsɪstəm/, innovative /ˈɪn.əˌveɪtɪv/, curiosity /ˌkjʊɹ.iˈɑ.sə.ti/, intellectual /ˌɪntəˈlɛkt͡ʃʊəl/
I suoni difficili per chi parla italiano:
- /h/ — va soffiata, non è muta: household /ˈhaʊshoʊld/, horrible /ˈhɔɹ.ɪ.bəl/, hire /ˈhaɪɹ/, hook /hʊk/, cliffhanger /ˌklɪfˈhæŋ.ə(ɹ)/
- Consonante finale — senza aggiungere una vocale dopo: curious /ˈkjʊɹ.i.əs/, translate /tɹænzˈleɪt/, innovative /ˈɪn.əˌveɪtɪv/, dose /ˈdəʊ̯s/, fortunate /ˈfɔɹ.t͡ʃə.nɪt/
- /æ/ — più aperta della “e”: vaccine /vækˈsin/, translate /tɹænzˈleɪt/, span /spæn/, translation /tɹænzˈleɪʃən/, mask /mæsk/
Come esercitarsi con questo video
- Ascolta tutto il video una volta senza parlare e annota le parole che non conosci.
- Inizia a velocità 0,75×, fai shadowing frase per frase e torna alla velocità normale quando diventa facile.
- Registrati e confronta con l’originale, facendo attenzione a parole come vaccine, innovation, ecosystem.
Cos'è la tecnica dello Shadowing?
Shadowing è una tecnica di apprendimento delle lingue supportata da studi scientifici, originariamente sviluppata per la formazione dei traduttori professionisti e resa popolare dal poliglotta Dr. Alexander Arguelles. Il metodo è semplice ma potente: ascolti un audio in inglese di madrelingua e lo ripeti immediatamente ad alta voce — come un'ombra che segue il parlante con un ritardo di solo 1–2 secondi. A differenza dell'ascolto passivo o degli esercizi di grammatica, lo shadowing costringe il tuo cervello e i muscoli della bocca a elaborare e riprodurre simultaneamente i modelli di discorso reale. La ricerca dimostra che migliora significativamente la precisione della pronuncia, l'intonazione, il ritmo, il discorso connesso, la comprensione dell'ascolto e la fluidità del parlato — rendendolo uno dei metodi più efficaci per la preparazione alla prova di speaking dell'IELTS e per la comunicazione reale in inglese.