Working In Oncology
Working In Oncology

Episode · 1 month ago

Drug Development: How Do We Choose Which Unmet Needs Get Treated? w/ Jeff Bockman

ABOUT THIS EPISODE

Unmet need is a huge driver in the development of oncology treatments. But when it comes to choosing the therapies that “make the cut,” it’s not that simple.

What are the risks involved? Where has efficacy been demonstrated in the treatment area and type? And the timeless question: who’s paying for it?

Jeff Bockman, Ph.D. EVP & Oncology Practice Head at Cello Health BioConsulting, joins us to share his experience and break down the criteria and considerations of how therapies are chosen and developed.

Here are the show highlights:

- Who are the players and decision-makers developing therapies? (3:18)

- How developers decide which therapies to pursue (15:34)

- How the element of risk complicates the goal of pursuing unmet needs (28:20)

- Pipeline activity, precision oncology, and more trends in biotech (34:24)

- Why we’ll see more “engineering of biology” in the next 5-10 years (39:28)

Check out these resources mentioned during the podcast:

Dr. Bockman’s LinkedIn

Dr. Bockman’s Email

Cello Health’s Website



To hear more interviews like this one, subscribe to the Working In Oncology Podcast on Apple Podcasts, Spotify, or your preferred podcast platform.

...o You are listening to working inoncology. A podcast and video show that spotlights oncology, practice staff andindustry influencers who work behind the scenes to shape the future ofoncology, the more knowledge the oncology community shares with eachother, the more we all grow, let's get into the show. Welcome to working in oncology. I'myour co host, Alicia Evans, I'm joined today by Jeff, Backman, EV and oncologypractice head at shallow health, bio, consulting C H, B C is a leadingstrategic consultancy, helping Bio Farma inflect value with their earlypre POC programs. Jeff. Welcome to the show. Thank you,Lisa, very, very honored, to be here thanks. I am excited about ourconversation today. I think a lot of our listeners are curious about whatgoes on behind the scenes at oncology drug development. So why is therefunding for this treatment of one diagnosis versus another? Who makesthese decisions and why right, I think I'll be able to shed some light on thesubject. I hope so. Sam Still, before we jump into the show, can you tell ofyours a little bit more about you, your background and what you do sure. So I got to where I am through a hard work and and serendipity. So Istarted an academia did the the PhD route when the post dock route and thenafter that, went to a start out, biotech working in Panser and in fetisdisease, as my background was originally in infectious diseases andwas with that started by out that for a couple o years, I was one of the firstsciences than to join it and, of course, the back got exposed to some of thefinancial and investment side of being an early stage, biotech gaming withsome of the investors etc. And then I left the biotech and Stiller startedkind of consulting on my own and ultimately consulted to the legacycompany of where I'm at now, which is a divine health which you know, wasacquired and became Jello health file consulting so, but that that kind ofshift was a lot happens, stamps right. It's not like I sat down and said. Oh,I want to be a consultant, don't even know what it was so so it was reallyjust a you know, opportunism on my part, connecting with you know the rightcompany, a great group of people, particularly the the founder of thefine health who was now the executive chairman and really enjoying the kindof mingling scientific, clinical and kind of commercial elements that we doevery day and all the multitasking right at it's never a dull moment. Somany different agents and companies with different questions and concernsthat we're working with across all different tumor types of cancer, aswell as the work we do outside of cancer. So it sounds like a prettybroad range of experience. There yeah well there even other diversions anddigressions along the way, but you know maybe we'll get to those later. So inthe world of therapy development, there are several different players in theprocess. Sod names that were familiar with, or some that were, but we're notcan you help go over like who are the usual players who is making thesedecisions who's? Developing these therapies? That's a that's the big question! So,first of all, I'd say is that you know the the industry, the Bio FormaIndustry is made up of variety of key state colder right. There are the farmof companies, obviously who most people know who about right, the murks and thefigers and the Bristol Lierse Rosh an intact, and then there is a whole groupof what will call the innovators not to say that Farma or an innovative, butmuch of the novel and New Drugs that...

...they are ultimately bringing to marketare deriving from these biotech and that the biotech who are most of ourclients, at least in oncology and those biotechs, obviously are funded by intercast. By and large of these days,you know increase they also public money, because I can readily go to themarket and raise quite significant funds during this past a year and ahalf, and then, of course, you know part of that ecosystem to, or you know,the regulatory agencies and the different comp of different countriesetc. But but if we think of it, just more simply in terms of the funders,the vcs, the developers and, ultimately the marketers form up and then theinnovators being the biotech, that's kind of the kind of the tri part tipcore of kind of where this all I gets and hopefully- and I think it'srelatively true- you know much of what is being funded at early stage andthese innovative companies is trying to address. You know high unmet need areas,that's not to say that every one of them you know if they were to beapproved, is going to change the treatment paradigm. Sometimes theimportant improvements can be smaller and incremental, but you know mostlythey are trying to look for. You know where there are significant unmet needs,where you know either in large tumor types that everyone knows about wherethey're still unmet needs like cur to positive breast cancer or much smaller,knit type of tumor types. Where you know, maybe less attention has beenpaid in part, maybe because they're very challenging spaces to the work inlike Leo Blastoma or even some of the rare rare star, Comas, etc cut. So whenwe look at a typical therapy, can you help us track kind of the developmentprocess, so maybe of how popular medication or therapy like K Trot orsomething? Can you help us check how these how it got to help and how itcame to market? Oh, yes, well, yeah, at a high level. Yes, I think one of themore interesting things about Karuta is the fact that in many ways that was serendipitous in the sense that thatwas a program going on. I think within Organon that was acquired by sharingplow, didn't have much attention to sharing cloud that I'm aware of, and Idon't want to misspeak, but as far as I'm you know, I don't think it was ahigh profile program at the time. Then I that's a start up is that well, noSiringo was another large farmer company and the A I was acquired byMark Right, because there's a lot of Ma amongst large forma right mark,acquired sharing plow is are required. Part Davis Order Lambert. So you know alot of that inter large farm. A M NA is very common, so you know murk ends upwith this sharing plow organ on program. You know bumping around internally thatyou know, I'm sure, had some strong champions, but you know I was at thattime. One has to remember that the idea of being a therapy of cancer or, asit's also called now kind of eminance you as I call for short io therapiesfor midling. They were not the the hot topic they are now and in fact, back inthe mid two thousands, and certainly before that they were pretty much forboten in any ways because they're a because there have been so manyfailures. You know the field of the people who were researching at thatpoint, where you know called Tumor biologist to mere knowledge. Is thatwere kind of doing this, and the kind of the main programs that have beenbrought forward back then were mostly cancer vaccines, which were kind ofdeveloped with framework similar to the idea of developing. You Know InfectiousDisease Vaccines, which are you know, really used to prevent infection verydifferent. This idea of trying to treat...

...an act of cancer for all sorts ofreasons that you know, maybe we can go into leader. Anyone wants to discussonline. We can, but so there was a lot of failures in this cancer vaccinespace, because it was mostly what was defining kind of Mino therapy that nowthere were a few approvals and success as one of them even was fearing plow.You know in terms of interfere on ILE to that was developed in you ultimatelykind of really brought forward by my car on that was acquired by artists,and you know these had some glimmers of very interesting activity, particularlyin like melanoma or being now some personal, my kidney cancer, but theywere highly toxic, not very well tolerated. Only a small percentage ofpatients responded and an even smaller percentage responded really well, soyou had a field for a long time that you know was defined by those. Fewagents interfere on isle to BCG for Bladder Cancer and then just all thesefailures, mostly it cancer vaccine. So it wasn't until really like twothousand and twenty eleven on. Suddenly the world changed right, you had bemsup Debo, we ballamacree you've had murk Katuti membris m a approved. He alsohad Dendreon Cancer Vaccine Provence approved bit of a Nich player, but it'sstill, you know generating revenue. You had your boy also from from tms I getthe LUMMA approve. So now, all of a sudden, you have these what are mostlyantibodies to one or you know, PD, one P D, one that check one inhibitors.These are t proteins expressed. You know on the TCL end or tumor that arebasically responsible for silencing the immune system right so essentially whatthe cancer does is. It creates a permissive environment for itself.Greets is even a suppressive environment that blocks the bodies,kind of normal ability and desire to reject things that are wrong, whetherthat's you know a tumor or I an invading you know bacteria or virus,and these antibodies basically unblocked that blockage and allow theimmune system to see that the tumor and they, although they don't work in allcancers and they don't work in all patients in all cancers- and you knowsome tumors they, you know work much better like melanoma and ORCS and oncancer than others where they, you know, really have minimal activity likeprostate cancer. They have created a massive sea change or a Paradisi andhow we think about treating cancer. So you know what Merk tms and all theothers have done is what kind of Farma generally does as they invest a hugeamount after first approvals in life cycle management, so murk has done anamazing job. They have you know, I don't know a thousand plus,probably more, on going clinical trials with Caruta alone must lyin combination,a combination with temo and combination, Fredo therapy combination with smallmolecule, kinase inhibitors and in combination with other novel IO agents,including other IO and a body. So a lot of the news coming out of ASCO, forexample over the weekend and through the report of this week, will aboutother new targets besides PD one and L, one like nine, three or Tengen, etc.These are kind of the next generation. I mean the oncology targets, so that'sa you know sounds like a long story, but that's only a you know a littleteeny peak into the kind of the you know what it took to ultimately kind ofbring that program forward. It took scientists who are true believers inkind of the value of the immune system and fighting cancer. It took thediscovery of these particular targets. It was certainly you know lucky thatsome one of these first targets proved to be as effective as they were,because you know some of the other ones haven't been. So you know Jim Alisandathere that yeah certainly is me, but so...

Jim Ellison got the Nobel prize forthis, but many others contributed to kind of exploring that that they'recalled checkpoint inhibitors, this checkpoint pathways and now they'rekind of the foundational cornerstone of treatment. You know either in aparticular line or in multiple lines across many many different cancers with,as I said, a huge amount of continued development in other tumor types, otherlines of therapy, other combinations going on right now there, or at leastsix, I think, approved checkpoints. Now murk is the biggest one followed by you,know, b MSS and then you know, got fizer and as presentia Broccan en techfor generone. You enen now also better that are out there, but you know itit's competitive, but you know the the Bahima in the room is mark catrutosyeah, that's on that we are, most of us are familiar with and it sot like theyare continuing innovations in justice, just in Patrona it does n't it true,but I I mean I I olaso. There is an organization called Cancer ResearchInstitute, CRI, which was actually founded by believe it was the daughter,coy Dr Coley here at what Ultimo became a morison. Kettering was considered tobe really indeed, I do know what he would call him grandfather, freegrandfather, Oa of give me the therapy because he was treating patients withwhat was called Kolis toxin so that you know, but it was never and it wasactually used up through the six as never formally approved, but in anyevent cri you know has funded a lot of the t research as a not for profitfoundation in Aminocles, and they also do a lot of tracking and I think, fromtheir recent numbers of I recall correctly. There are probably threethousand trials going on with you know all the different checkpoint inhibitorsthat there are so con Truda up divo. You know Luteo, but then co who mindmissing anyway. So I mean all of the players but but buying or or of thelargest amount of clinical trial activity this with Meran catreunderstandable. So when we have so many different avenues, how do we decide orhow does do the usual players he's the side which therapy to pursue? How dothey make that? Is it just a question of all the money? Of course that I meanwithout the money I think it happened, but what other factors do they considerso so many factors kind of going in to try to figure out what to bring forwardand and the kind of the questions and the degree that these are explored andhow deep and drawn certainly varies between whether that question is beingasked interning within a large farm, a company or whether it's Neem beingasked by a biotech company, let's start with the biotech company since that'swhere a a lot of the innovation again all of it, but a lot of the innovationthat begins right. That's where a lot of the innovation in out of selftherapy has been, which is a burgin area, and there are you know, a numberof approvals already where team therapy began by and large, and there are anumber of proves there. You know, for you know rare monogenetic disorder, soso the Bio Tex are kind of seen as the warehouse of innovation. If you will,and increasingly a large component of the pipeline as it's called the drugdevelopment, nightline of large farmer is deriving from you know, external tothe farm itself, so not from farm as own internal research. You know, Ithink it's honestly varies by company, but I insome companies- it's fifteen percent, maybe but seventy five percent of theirpipe line is coming from external. You know deals either licensing and aprogram from a biotech or outright acquiring that the biotech right likeAmgen recently acquired. You know a company called five prime to get someof their antibodies. Another programs,...

...so owing a biotech, is trying to thinkabout kind of what to develop. Part of that question depends on kind of whatwhat their reason detrey Ou know. What do they have for I mean if they're adiscovery company a platform company right, maybe they've, got some novelinteresting way to generate antibodies, which there are many you've got thoseall right. Well, all right! You can generate these anti bodies. They may dosome cool things that others can't, but how do you decide what the target rightthere lots of targets? So that's one of the first gating things right, because,while the vcs, like the fund innovation, you don't want to be all about, youknow risk after risk of the risk lay on top of each other. So very often youwill see bio text in order to prove theirplatform, but also to take some risk out of it going after well establishedtargets, many of which they already be approved. Right, like her too, theamount of drug development around her to, despite the fact you've got herCeptin you've got for Tina. You Got Kasia. You've got an hair to you've,got a number of you know multiple. You know and they're mostly biologics, butthey're also small policies approved in the space and yet they're still unmetneed, particularly for advanced date, breast cancer patients. So you know ifyou map, where much of the activity is across, follow the Bio farman industryagainst targets. I think her to is a belied and then ef R, which there alsoapproved drugs, and so you know you do see a lot of attempts to de risk. Mygoing after these and well it's kind of easy to say. Oh we've got too many. Wedon't need any more. That's just a me to type agents not going to bedifferentiated in some cases. You know these can be differentiated and providesignificant clinical value to patients. So that's kind of one of the firstthings that happens, particularly with really risky platform. So when AnteponoPlatform, it's pretty well established most of those companies. Yes, they maygo after her to but they're, also going after other novel targets, some ofwhich have been more recently balade because there've been recent approvals,lint troke, to which there been a recent, a DC approval and a bin Drugcontigit approval for the more risky the platform, the more likely they areto go after these. Well validated targets like there are a lot of aboutto sell therapy companies and mostly their league programs, are going underCNINE teen, which is approved for other self therapist. You know- and you knowyou start to be selling foma and cut Masita et Cetera, because the everyonein the investors are very kind of scared of we're going to take a brandnew novel unbelied target, take a brand new UN validated approach and put thetwo together and just double. You know magnify our risk. So that's the firstconsideration is the target and then, of course is where do you develop itright? which indications do you develop in and that thinking you know generallyhas to start even before you start getting early signals and earlyclinical trials, which of course is going to have more definitely tell youwhere to go, because you need to at least be thinking about where you mightend up in advance of doing it can just kind of wait around and and just beyeah and then you're just scrambling right so and that's where we spend alot of time with our clients. These are early stage, as you said, you knowhelping them inflect value with creos pre POC asset, so helping them say youknow, I've got an novel platform. Should you go after CD, nineteen orBesma, or her to or each or should go after something more UN validated andthen once having decided on the target or the Marindy have the target whichindications are best if you're going after her too sure you can go after youknow a number of different lad line, therapies in an Franciae, but her to isexpressed in other doery like gastric and even small percentages, anothertumor type, so maybe the better thing to do is go for a nich approval in apercentage. You know a Melentil defined...

...some set of other tumor types thatexpress you know or some set of patients express or to so. Those areall the questions that are kind of going on internally, as well. As youknow how much money do we have what's our burn rate in order to prosecutethat clinical trial development? What do we want to be when we grow up? Do wewant to bring that drunk all the way through to mid stage face todevelopment, or do we want to license it out or we hope to get acquired? Youknow early on so you know so. There's there's true science and biology thetarget being asked about there's clinical development questions beingasked and there's kind of strategic. Like you know, what's the trajectoryfor the company all wrapped into the financial considerations of how muchmoney do we have how much could be raised at some? So it sounds like it'sa balance that, as be of all those different factors, absolutely it's avery delicate balance with a good, healthy dose of luck. As you know,having you know, experience is important and that's one thing biotechhave nowadays increasingly that they didn't have. You know as much of evenfrankly, you know ten or fifty years ago was you know a much more matureseason group of people leading the company right. These are people you areout of Parma or who have been in one or multiple other on no text, so they kindof know what's involved, because you know it's one thing: to choose thesethings: to choose the target: To choose indication to validate your platform tostart clinical development, but there are a lot of complexities around C MCmanufacturing for some of these agents. There's regulatory complexities notjust for us, but differences between you or you- know, Asia, etc. So a lotof different skill sets, you know, are required ultimately kind of bring theseprograms forward far enough and then ultimately you know to market, and sowe did talk. We talked about biotech. What about some of the other players?How do they are? There? is their process their that process similar proa similar? It's obviously different, if you're, a large farmer, you're, not tosay you're, not concerned about money, because you don't have infinite, can abit more at a lot of money on hand, they invest a lot amount into rnd s, apercentage of their revenue. So they ask many of these questions. They askthem more. Deeply, they spend more time analyzing them. They even go outsideright. I mean as big as these companies are. They often go outside for helpdoing things, everything from patient research to just kind of more kind ofclassic kind of market research to you know the big strategic questions thatthey need, El, bon and so on. So it's Lang is just massive ecosystem of allthese different players that are involved, something we haven't really talkedabout, is academia and how those efforts play into the Pipoo mentionedthat yes, because this is an interesting, maybe even a littlesticking point, because many of the so I said that the innovation engine bylarge is biotech they're generally, not inventing it out of nowhere. Rightgenerally, biotech is coming out of academia where's that research for thethose platforms or those novel targets, et Cetera, coming from all of us, thetaxpayers and I h funding, which is why it's so important to find an ah, butalso at the same time, people question well, but you know- and I at justfunding all this, what a we getting! What are we getting back now? You knowwhen you ask that question depends how you, what time frame and how you answerright. Ultimately, we are getting back because we're getting these importantdrugs, but there are a lot of intermediaries along the way, sowithout getting into policy or other things like that, an our tax dollarsand the CO insurance yeah. But at the end of the day you know it is withinacademia that the real engine of innovation, now that gets taken withinthe biotech and it gets kicked up significantly and it gets formalized inorder to you know- enable it to be productive to be credible to ultimatelyget approval right because you know...

...most academic labs, even thoughincreasingly they are kind of starting to develop some drugs and bring them to.You know at least go preclinical they're, not necessarily set up. Youknow and don't have the expertise. You know once you're kind of into earlyclinical, although some some are doing that. Certainly you know and that'swhere the biotech and then the form of companies come into play. But many ofthese biotech are founded. You know by either of the entrepreneur scientiststhemselves or they're founded by you know a DC or early stage BC, whichthere a number that just go out and scout and say: Oh, you know, our teamhas found this really interesting cool mechanism or target or new platform atthis university, and that can be you know anywhere in the world. Frankly,and you know, decides to build a company around it. That's kind ofgenerally how it goes to tell if I understand correctly so, like thefoundational foundations are usually set, are often set by academia. Thefoundation of researches often coming out of academia, but not always, butoff of it and then generally goes to biotech and then to Farma, and then theformal, the certainly you know there are biotechs that are alreadyestablished that you know, will license programs or ip or technologies fromfrom academia right. So they've already started with something and they needthey're either acquiring additional pieces or maybe something orthogonaland Barma also does increasingly look early stage and there are even groupswithin large farm up for doing kind of early stage. Investments and most Farmahave their own corporate BC group that are also making investments. You knoweither investing in the lab and some type of early collaboration orinvesting or helping form an new co Co investing along with more traditional,you know, vcs et ce, so what I'm talking about is just that you know. Isit just a last work? It yes, and there are many many layers and many more youwant as an complexities that to do this so often in practice. You know the ideacomes wise there, a treatment for one diagnosis versus another, and I know wetalked about reasons why you know therapy, but can you kind of expand onthat yeah? It's a really complicated question, part of it. I do what Ialready said about risk right, so some of those, if you're, choosing totake out some risk by going after a validated target. Mostly that's goingto take you to more validated indications, which also, by definition,are also going to be more competitive like breast cancer. The other thing sothe other side of taking risk out is not going into places where there ishuge risk. So there are tumor tights and I'm not even talking about smallNich tumor type drink, because there are tumor times where only a hundredpeople out them or a thousand right there's, not not even orphan, it's someorphan or some submoron diseases, and clearly these need to be addressed.They also need to be abreast when they're, just you know not cancers, butjust other very rare diseases. I will put that aside for the moment, even inkind of bigger, more well known, tumor types, there has been a hesitancy topursue because of the perceived risk that an often casesis a real risk in these filmer types. So, let's just take two, for example,Leo Blas Film, very high on met, need right, absolute, very poor outcomes.You know angry at it: cancer another very high, a man need even biggerepidemiology than than Glioblastoma, also very high on that meet again. Innow cases these are generally diagnosed late, certainly mareotic cancer, mostregias late, good percentage or not perceptible. What do you do? Well, onecould say: Well, there should be more clinical development there and thereshould be, but there's a size lit for...

...the patient. That's yes, and but thereis a sizable amount of clinical melven there. You know, but part of the reasonwhy maybe the amount is not as proportional to the unmet need, andI've done some mapping before and others have to we're just kind of plot.How many drugs are development against either the epidemiology or against theactual unmet needed, and the need is best express either is one or by yearsurvival. You know it parallels pretty well, but there are some. You know,kind of major places where there are gapped, but something like pancreaticor or Gbm. There have been a lot. A lot from drug fills all sorts of differentmechanisms, all sorts of things that people have done and fell. Your afterfailure now you know, I don't know that now we should go into the reasons forthose rether. Differing first of all. GBM is very heterogeneous. It's notlike one thing, so you know a given target. While it may work for a certainpercentage of patience, you know, may not work for all and since we may notknow how to identify those patients up front and means when you do a clinicaltrial, your signal is going to be drowned out, so the drug may fail andfor Pangrams you know. Also the biology is complex, because an grandi cancerbasically builds this dense, fibroid struma around. It makes it very hardfor drugs of any sort to get to the cancer. So for those, in other reasons,you know they're both highly you know they have high kind of gemo resistanceand other things just makes it really hard. So we've seen antibodies, failsMamaconas, I better spell Vectura Ion Timo agents, bail, sell therapies,vaccine mean time and a gat it in both these indications. Things have failedand when things fail that much, it makes it hard to convince someone tofund doing research in those areas. Now again, it's not like there's noresearch. There is a lot of clinical development in these areas, but perhapsnot as much as there should be given their unmet needs because of o thatoverhang of the failure rate in those tumor types. So that is wherefoundations can be helpful right. So there are many foundations that havebeen started, often by either survivors or family members. They may have wellto do. You know to begin with and can start the endowment, but you knowthere's some great foundations out there in solid tumors, some of whichare obviously well known, like an bress cancer, sus and Comin, etc, and youknow others in in Hemolysis, like the Maloo Research Foundation or the Keniaa Homo Moundaneta. These are very helpful because part of their mandate,so I can speak more fluently to the kineless less because we worked withthem for over a decade. Part of their mandate is to fun where bio format doesnot so go for the riskier things to they're they're filling the gaitthey're filling the gap yep. So that's what the foundations can do is fill thegap either by the tumor types that aren't getting as much attention asthey should or the therapeutic approaches that you know maybe they're.You know they're more swinging for the fences, they're very high risk, that'snot where vses may want to fund or far MO wants to go, but if they were towork you know maybe could be. You know groundbreaking, and I thank you forthat. It's Oreque tion that comes up- and you know, goes to your mind off andlike I wish. I wouldn't want to help this person, but what tools are there?What tools are available? So you work with so many IO text? That's aconsultant! What trends are you seeing in? Yes? So one of the May not be the best metric,but it's a very tangible metric that one can use, as you can look atpipeline activity right. So where is the Clinical Melman time line? And youcan also look at deals and you can look at funding. You know bess the moneygoing see ing or series a funding like where the money, where is the money,going either funding money or do you making money that includes licensingand acquisition? So you know over the...

...past seven plus years, they're reallykind of two big categories where investment has gone. Investment startup steal, making et CETERA. It's precision, oncology right. These aretargeted agents going to specific molecular changes right, gfr mutations,Al Mutations, F, Gfr, mutations, CR, able mutation so at least are solidtumor, because that's a very defined molecular target. You can define thepace of population. You have a much higher rate of response because you'rereally defining who should get a given drug and you actually have a muchbetter kind of development chance right because gay we were, as I gave in thekind of big counter big example, negative example, or for Gbm orpancratic. You know you may not necessarily know who's going to beresponsive, and so your signal of those who are responsive may be wash down inthe trial. I will re out negative so that type of precision medicine and wejust literally had approval a few days ago for from engine or their rast,targeting agent grass had been like the being struggled for the Biafaraba forde Games or any thing just couldn't drug it. And finally, you know peoplefound that there were some particular mutations within rasts that could bedrugs. So now we have the first RASP drug from an Gen that Gonta prove justyou know, days or maybe a week ago, so precision oncology and then I Minaco, Imean em me oncology for a period of time say from like twenty fourteen fifteen through about twothousand and eighteen was like probably two thirds of the highest value deals that were being done,meaning either the money up front that a farmer was going to pay to a biotechor the overall value of the deal so including downstream payments, bilstoneand etc. It's kind of equalized a bit over the past few years, with kind ofmore of the precision medicine you know taking got more balanced more, likekind of fifty fifty for these high profile deals, and that probably istrue overall and but even in the most recent announce us we've done for, likeyou know this past the year today or two thousand and twenty two years today, looks like again kind of a lot more of a push towards the given coincyagents. Again I mean people are very enamored of that and and with goodcause, because you know tumors are very complex, they're classic they'reheterogenious. They change under treatment right there, a littleDarwinian experiments going on so the minute you treat them that at tumorsgoing to respond and counteract what you're treating it with. So it's veryhard, if you have you know one agent or even a tool, kid of ten agents to sayyou know, I'm going to go against this, this phone that constantly keepschanging. When I do something the immune system is built for that immunesystem is plastic. Adaptive Heterogeneous can change in real time,just like the tumor. So in many ways it is the best matched to deal with acancer, and I think in part that's why well that's the kind of the thebiologic and clinical rationale for why people are and should be so interestedin kind of harnessing immune system. I think the very practical reason is youknow the Trut is going to be the largest selling formas product in a fewyears of any, not just an cology period. So you know this is a very big categoryand you said it before chasing the money where the money is, people willgo and they'll keep going and they'll go again and again so sound. I cancheck off all the boxes. Yes, the check points in particular check off theboxes, so Taticseva experience, so you might be the best person to answer thisquestion. What are your predictions for? The future of oncology, pharmaceuticaltherapy development and we've gone over...

...a couple things? So what do you thinkis in next frontier, so the next frontier there are lots of famousquotes about predictions E, mostly wrong. A but nevertheless, I think, anthey're. The prediction that I'm going to make is less about what willdefinitely become the drugs of the future, but more about the types ofapproaches that I think are going to be heavily invested on unfocused in overthe coming five to ten plus years, and I think it's the idea of moreengineering of biology to make the therapies we use more multifunctionaland perhaps we regulate or controllable in the body, so whether it's a antibodythat can be controlled externally. What does that mean? Well, that means thathave you've got side effects with a certain antibody and you build insomething that allows it to be active in one configuration. But when you givea drug, it's no longer active right, you can give a small mine or, or theother way around, you turn it on and off and the same things being done withself therapy. So this idea of conditionally active and controllable,as well as targeting multiple things right, because we just talked about howplastic and diverse everges the tumors are. So you know, if you can, if youknow you need to target her to and ultimately kind of three other keytargets that become important when you know when you matula her to and thetumor Tristis Skate, if you can hit her to and all thoseother targets at the same time. Wouldn't that be pretty cool about, sopeople are looking at ways to do that. You can do that with Gen editing orthings that are kind of like Gen therapy could do it with certain typesof self therapy. You can do it with RNA based therapeutics. You can do it witha certain multi function, Alata and nobody or antibody, like muletus thanyou can build in that regular to the regulation that I talked about beingable to kind of control that to have better quality of life to safety, forthe patients, and so you know that kind of more complex or more refinedengineering or viole engineering, as I think where a lot of things are going,it's going to take a while to get there, but you know ultimately, whether thatmeans we're talking about some matene robot. There was an interesting counterpoint at at a conference that I attend called and speak at home. I have threed sixty every February gerin Manhattan, and that was one of the interestingkind of point counter points between two kind of luminaries and the oncologyfield was kind of where the future is and the idea of kind of romont. Nowthat doesn't mean their little. I mean I e Macon base things that are but a,but the idea of robot being something that is responsive. That can domultiple things that can change in reaction to changing environment,that's what's kind of meant and that's what I'm meaning with this more complexand interesting engineering that is so exciting to be a to cacotrophic. Butyou know there people you know some of these are in. I some of theseare starting in the clinic right now to so wow. That's so exciting! It's so yousaid it's already, starting that some of them are already going into theclinic. You know the more the early generations of these things yea thefirst steps yeah the first steps, but soon maybe we'll get to Oh yeah, an ano but well, and there you now that's one thing too. So going back to thatquestion of kind of. Why are certain cancers? Do they not have as many newdrones or powerful trug etc? Again, it's not for lack of trying like athird wrothley of the overall biopharma Ceuta pipeline, so wherever that'scoming from wherever in the world or biotech or Farma or whoever a third ofthat pipeline is cancer. That's a lot! That's a lot of drugs! That's like fivethousand six sand, maybe more...

...drugs of all sorts that are beinglooked out to try and treat you know sometimes a very specific, singularsubset of one particular type of cancer, and sometimes you know trying to goafter every cancer. It's a very broad, acting agent like to trude up so again.It's not for lack of trying may not always be the right approach. It mayalways be the smartest approach. As you know, lots of other things complicatedecision. Maybe it's not just a purely rational process to perhaps not lack ofeffort, but lack of success. Yes and then sometimes lack of focus forsometimes getting trapped within a certain mindset. Right, like the immunesystem, will never work. Yeah I immune dine, will never win right. That's abit to stop there across getting away from dogma. You know is something thatis harder than you should think in science, but maybe that's a broaderconversation. Yes t. This has been a really greatconversation and discussion that any of our listeners want to reach out to youwith any follow up questions or just want to reach out to you at all. What'sthe best way for them to do that, so there's there's two ways: The way thatmost likely that I would see easily and not accidently miss would be likereaching out be a linked in right, a linkin connection and messaging. Theycan also find my email if they go to chill help bile consulting com to thewebsite and go to the who we are and the Bios, and I think the emails foreveryone are there. It's just that. I get so many emails, but there is thechance an if I don't recognize an email coming from someone. I don't knoweither the San System will block it or I just won't see it because I get somany emails, so we to disappearance to the ether I've had the so I will add the link to your linkedinand also the cello website here in the show notes for anyone who would like tofollow up again Jeff. Thank you so much for adjoining us today. At least wethank you. It's been been great. Talking with I take care of you to bye.Bye, you've been listening to working inoncology to ensure that you never miss an episode subscribe to the show inyour favorite podcast player. If you're listening an apple, podcast, we'd lovefor you to leave a quick rating of the show just tap the number of stars. Doyou think the podcast deserves? Thank you so much for listening until nexttime. I.

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