Drug Delivery Differentiators with Syncromune's Eamonn Hobbs

This inaugural expo is a fantastic opportunity for biopharma companies and contract manufacturers to evaluate the latest and greatest from the comfort of your desktop or mobile device Conveniently . We've broken down the lineup into upstream solutions on July 30th , downstream solutions July 31st and quality analytical and data solutions on August 1st .

It's absolutely free to register for this series of short , digestible and interactive sessions . Just hit the link in today's show notes to register for BioExpo Live . Today , in the biopharmaceutical business , delivery is at least half the battle . We make tumors go away in petri dishes all the time , and of course we do .

The tumor can't escape , its cells can't multiply , the drug can't escape and go on to wreak systemic havoc .

It's a tightly controlled environment In human bodies , though the challenges associated with getting a therapeutic molecule to its target and keeping it there and perhaps only there are biologic , chemical , physical and engineering problems that , left unsolved will never allow biotech builders to bridge that gap from academic exercise to clinical success . I'm Matt Pillar .

You're listening to the Business of Biotech and on today's show we're talking with a man who's spent the past four decades working on the interface between advanced diagnostic and therapeutic products and the human patient , that interface being delivery technology .

Eamonn Hobbs is president and CEO at Syncromune , a phase one drug/ device combination company whose SyncT solid tumor therapy platform combines partial oncolysis of a tumor with infusion of a multi-target biologic drug directly into the tumor . It's a novel approach , using novel T cell science and a proprietary device to deliver the tumor .

It's a novel approach , using novel T-cell science and a proprietary device to deliver the goods . On today's show , we're going to get to know Eamonn and we're going to learn how Syncromune is building a holistic biotech business that's focused as much on delivery as it is on drugs . Eamonn , welcome to the show .

Well thanks very much . Great to be here . As I said , hard to believe looking at you , but 40 plus years in this business working on this interface that I referenced , the instrumentation and the mechanics that interface drug delivery and diagnostics with the patient and , more so , building businesses around that interface .

It's a very unique , interesting niche I would say that you've built a very successful career in and I'm curious about how that all got started .

I mean , I know you were a bi , like a bioplastics engineering guy in your undergrad and coming out of school , at what point did you say this is inspiring enough for me to want to go build a career around , as I said , this sort of interface between biotechnology and human beings .

As a matter of fact , I didn't think that biomedical engineering , material science or even medicine was where I wanted to go . It was very clear when I saw Neil Armstrong put his foot on the moon . I said I want to do that , I want to be an astronaut , and I'm no question .

And I studied real hard and and did everything I could to put a path together to have a shot at getting into NASA back way back when in the 70s , when in the 70s and I got an appointment to the Air Force Academy and ended up going entering in 76 , which was the first co-ed year for the Academy , which was a big landmark , but I thought I was on my way

.

I mean , all my hopes and dreams just went poof , uh , just like that . And uh , I didn't . I had 2020 vision at the time , didn't have these and um , uh , I uh had to , you know , had to make some really serious life decisions , uh , pretty quick .

And uh , you know , the uh , the uh the Air Force said you know you're going to have a great career in the Air Force . Don't worry about all that flying stuff . You know you'll , you'll have a great career in a missile silo or pumping gas for all your pilot buddies . So I did the only thing . I thought really great , good luck .

I ended up at what was called Lowell Technological Institute at that time and now called UMass Lowell , which had a great engineering reputation and , more importantly , would take me in the middle of freshman year , which is unusual .

So I was an advanced placement student , so I caught up quickly and I entered as an electrical engineer because that's what they said I could get into . My oldest brother was an electrical engineer and my father was also so , along with being a lawyer so . So I said , oh , that makes sense .

And then once I got in there , I I saw that the coolest engineering that was at Lowell Tuck was plastics engineering and I I was lucky enough to get into that and which was an incredible break for me and then bioplastics engineering became a creation of my own .

There was no biomedical engineering at Loyal Tech back then , but they gave me the latitude to kind of make it up as I went along .

So I took all the medical courses pre-med and even grad school courses that the university offered physiology , biochemistry , molecular biology , et cetera and just found I loved it and I thought you know , hey , maybe I'll be a physician . This is kind of my calling , it appears I'm good at this stuff and I like the engineering a lot .

My brain kind of worked that way and I was editor of the school newspaper , so I was a writer as well , which is unusual for engineers . A lot of engineering buddies and communications never been their forte , and they'd be the first ones to admit it , but I had to be an Irish , the gift of the gab .

So I thought well , you know I'm thinking this is the way to go .

Another incredibly good break I was hired by my first entrepreneur mentor in my career Bill Cook , who's a legend in medical devices no longer with us , unfortunately Passed away in 2011 , I believe but he hired me right out of school to come and join his company that was already very successful in primarily in cardiovascular devices in Bloomington , indiana , and I came

in and I was pretty naive At that time , coming from the Boston area , I thought Indiana was a city in Illinois , so I was pretty young and stupid . Now I'm old and stupid , but I was pretty green back then and I settled in finally , and Bill really took a shining to me and said you know you're doing great , kid .

What do you want to be when you grow up ? And I said you know , everybody called him Bill . I said , Bill , I think I want to be a doctor . And he said , no , you don't . No , you don't .

I know you and what you do is really cool , and that is , you have no trouble speaking to physicians and understanding what they need , understanding what they do and what they need and then you have no trouble communicating that to your engineering brethren back here at the ranch . You're a very unique individual and you know , pat yourself on the back .

That's a really important thing in the development process of innovations in medicine . That's what you do and that's what you really are passionate about . Of course , again , I was young and stupid and arrogant and said , no , no , I want to be a doctor . So he said , ok , I'll tell you what I'll . I'll . I'll pay for you to go to med school .

I'll send you to med school if you give me five years after graduation . And I said , done , he goes . But there's a catch you have to go up to . The chief of staff at IU Med Center is a dear friend of mine . It was a surgeon by the name of Don Shorten and he's going to put you through boot camp .

You're going to be his right-hand person until med school starts next season . And if you still want to go , you got it , and if you don't , well , you've had an incredible experience . So I did , and I didn't sleep the entire time . I learned how to sleep with my eyes open , standing up .

Don Shorten was the most amazing individual I've ever come across , incredibly talented , and I had a crash course in medicine , what it's really like to be a very active clinical physician , a surgeon , and it turned out , when you know it , bill Cook was right I didn't want to be a physician .

Patient care is really hard and I take my hat off to clinicians who deal with that morning , noon and night 724 , 365 . 724 , 365 . It is an incredible commitment to make , to be competent and then gifted in patient care . So I came back to Bill and said , okay , you're right , that was an incredible experience and I got it on my system .

I want to really really be that interface between medicine and and engineering innovation . And he said great . He said you're , you're smarter than you look Good .

And today Cook Incorporated is the largest medical device , private medical device company in the world with , you know , billions in revenue and still family-owned . Carl Cook , bill's only son , only child , is running the show and Carl and I just caught up a few months ago and it was really phenomenal to see him . He was my summer intern in 1980 .

So yeah , we've both come a long way . He's a great guy and very passionate , as you would imagine . So marvelous , but again in the young and stupid category . I looked at Bill Cook and said , hey , you know , this entrepreneur stuff seems pretty simple . I think I can do it .

So I decided to leave Cook and go off and start my first medical device business called Hobbs Medical , learned a lot , learned a heck of a lot . I learned that entrepreneurship is really hard . I was a young engineer with a young family and I had to give up an incredible steady growth opportunity job with cook to start my own business and live hand to mouth .

And uh , my wife , uh , uh God bless her , um stuck with me and and uh , we , uh , we got the business off the ground and ended up having a good exit with it . I learned about VC and I learned about how to position a company for an exit . And I learned about we were commercial , we were selling devices and it was all good .

One of the companies that bid for Hobbs Medical was a drug company called EZM , and that really was my transition into the world of pharmaceuticals . And EZM was a world leader in GI contrast media and devices to deliver it . So barium enemas , and , and the like .

Howard Stern the another my second entrepreneur that I got to work for , and and was a phenomenal mentor took me under his wing and I got a real belly full of what the combination drug device business is like from a contrast media and delivery device perspective . And back then it was really nascent .

It was so nascent , in fact , that um gi contrast medias were regulated as devices , not as drugs . Yet and and when I uh about the day I I joined the , it seemed the FDA made a landmark decision to recategorize GI contrast medias as pharmaceuticals .

So I went through the whole transition with EZM from device to drug in a drug device company Again , incredible experience and painful experience for the organization and for the whole team . But I got a real ground up education in Howard Stern and Phil Myers , the founders of EZM , to help finance it .

Howard Stern and Phil Myers , the founders of EZM , to help finance it .

I started AngioDynamics on the back of an envelope and it was a hard with Abbott on their Avokinase , their urokinase product , which provided an intravascular catheter to deliver the lytic enzyme into the blood clots directly and this reduced systemic exposure of the drug which could lead to strokes and other very bad things and also decrease the license time dramatically .

So here was a perfect example of how you can take a really great drug but make it way better with a delivery system and make it safer , make it more effective and just add all kinds of value without having to develop a brand new drug . So added a whole new life to abokinase .

The other product we were developing was carbon dioxide angiography using carbon dioxide gas as an angiographic contrast media , an intravascular contrast media Wild at that stage . And at that time medical gases , including CO2 , were regulated as devices . So we had very broad labeling . Basically the indications were use CO2 whenever it's appropriate .

So it was a pretty broad label to fit in . So it all looked good . So we developed AllSpray , had a great run with it at Engine Dynamics and developed CO2 . We got our 510K , had a great run with it at Angio Dynamics and developed CO2 . We got our 510K , had a great partnership with Abbott on the pulse spray On CO2 , not so fast .

We developed a proprietary injection system , really an angiographic injector that was built for compressible fluids like CO2 , which would displace the blood in the area of interest , creating a negative contrast zone , and filed that 510K as an angiographic injector with the agency , the FDA , and went through a number of cycles of questions and I got a phone call from

the project manager at the agency who said hey , congratulations , I just sent your 510K upstairs for a signature , final signature . You know you should get your 510K notification , you know , in a week or two . You know great job guys , and you know that was an odd one . You know great job guys , and you know that was a . That was an odd one .

You know good luck with it . And we were , we were popping corks and thinking everything was great until we we got a call from that same project manager who said this got kicked upstairs for some reason and it's on hold . Your 510K has been put in escrow , which I was thinking . Well , what does that mean ? I've never heard of that before .

So it ended up that David Kessler , the FDA commissioner at the time , and his team had decided that medical gases were going to be recategorized as pharmaceuticals , so our delivery system was no longer associated with delivering medical gas device . It was now associated with delivering a drug that was not labeled for that as a contrast media . So we had meetings .

I got to meet David Kessler many times because we were kind of a landmark precedent in combination products .

We were making it up as we went along . So the CO2 ended up needing to be developed as a drug and it was an unfortunate reality that commercially no one was going to pay pharmaceutical margins on a gas that you can get in virtually unlimited supply . I mean I'm producing a lot of CO2 right now for nothing . Virtually unlimited supply .

I mean I'm producing a lot of CO2 right now for nothing . Nobody's going to pay pharmaceutical margins prices for that .

So commercially the project became a non-starter and we negotiated with the agency and we ended up Coming to the realization we have to come up with another way of delivering CO2 that could fit in the device world , which we ended up doing a hand system that got by . But everywhere outside the United States our CO2 system was commercially successful .

So we sold hundreds and hundreds of those systems and CO2 angiography is kind of a standard of care these days . In the US it's still done by hand , but in the rest of the world it's done with a combination drug device system .

So that got me very , very well cemented into drug device kind of being my thing , and more opportunities started to come around and my team and I took Ingenidynamics public in 2004 . We had a great run . We were the best performing medtech ipo that year . Uh and uh . We were uh , forbes . Uh , top 200 growth company . Uh , we're a business week .

Uh , top 50 hot growth company and uh , we're just crushing it . I ran it as a public company for five years uh , which is about the average for public company CEOs shelf life and then was promoted to co-chairman in 2009 , which is code for you're out of here .

So the board thought it was the time to bring in a Fortune 500 level CEO to really drive the company . It was an extremely successful company . On my watch . We got it to over a billion in market cap and it was a great return for the shareholders , great return for my original investors at EZM , and life was very , very good .

So that was 2009 and I had to decide what I was going to do with myself . So I decided I'd join a bunch of boards and try and give back frankly to young entrepreneurs . And one of the companies I joined was Delcath .

That had a very interesting combination product system in oncology and many of the products at AngioDynamics ended up being in oncology because the interventional radiology community was migrating that way minimally invasive , focal oncologic therapies . So I had a good base in oncology and the Delcath clinical data .

They were phase three , developing a ocular melanoma mets to the liver , new therapy which was a drug-device combination where the vasculature of the liver was isolated and the liver was exposed to very , very high concentrations of melphalin , one of the original cytotoxic chemotherapeutics , and it would kill the cancer and , amazingly , the healthy hepatocytes , the healthy

liver cells were virtually immune to the chemotherapy and when you think about it , the liver filters poisons out of our blood , so it made sense that the hepatocytes be able to tolerate this .

If the chemo got out of the liver it would decimate the bone marrow and lead to death or at least neutropenia or thrombocytopenia or both , grade three , four , really , really toxic .

So it was very important that the device do its thing and it involved a high flow blood filtration system that would filter the chemo out without damaging the blood , which had never been done before . So it was a really intriguing project and required a lot of innovation , and these patients were terminal without an innovation .

So it was incredibly gratifying to be able to add significant quality life to these patients' lives , where they really had nothing that was working before . So a belly full of that . We published our interim pivotal phase three data . It showed incredible efficacy and the company's market cap went to well over a billion about $1.4 billion .

It was $28 million when I joined the company and we thought we were cooking with gas .

We filed our NDA for the combination product and got a complete response letter which was a bit shocking , where they said hey , we love your data , it's really great , but you changed the device during the phase three trial and we want you to repeat the study with the same device .

We also your study design included a crossover provision that allowed patients who failed the standard of care which they all failed to cross over and get the therapy if they still qualified , which was ethically a very reasonable thing to do , but unfortunately on an intent-to-treat basis .

That meant the Kaplan-Meier curves were overlapping because the patients that crossed over did just as well , so there was no difference between the control arm and the treatment arm when you accounted for the crossover , the control arm and the treatment arm . When you accounted for the crossover , when you subtracted the crossover , compared to historicals .

First off , all the crossover control arm failed to get there . Two , if you compared it to any historical data , all the patients died . So it seemed really harsh that the agency was throwing the crossover provision in our face .

But during the course of the execution of that trial , the FDA had made a big shift and said the crossover is really , although they're ethically attractive , they really do a disservice to getting the new therapy approved . You really need clean data . So you've got to randomize people and not cross them over . So we suffered through that .

At that point we were looking at having to repeat the trial . It was an eight-year process . I handed the reins over to my second in command , jennifer Simpson , who ultimately ended up getting it approved last year . Her and her team ultimately ended up getting it approved last year her and her team . So a great , great success .

But I went on from there to another pharma company that I was on the board of . That called Antares Pharma , which made combination products , auto injectors and bio betters , taking existing drugs and making them better by applying a device technology or a transcutaneous delivery technology or a depot formulation really , truly bio better . And it was quite a factory .

It worked with all the big pharma companies and developed a very , very innovative and proprietary technology for them and would manufacture the products for them . So I got a real operational education there in development in CMC in a big , big device division in Minneapolis , plymouth , michigan , and it was really fantastic .

I took the job as a director going to CEO , because the CEO had left at a very tough moment . There's never a good moment to take a marvelous opportunity , but it was sort of a tag . You're it at the board level . You know , eamon , you're the best guy and capable guy to do this and would you consider doing it ?

And I thought the number two there , bob Apple , uh , was uh , the the obvious choice . And I said so , uh , the uh . The chairman , um , uh , had a new Bob Apple . They've raised him from a pop , as he said , and said , no , I don't think Bob's ready . Um , I love him like a son , but I don't think he's ready . And he knew him better than I did .

But I thought to myself if he's not ready , neither am I . He looks pretty good to me and so I took the job on the condition that everyone would agree I could develop Bob and I was quite confident I'd be able to do that .

Turned out that was one of the hardest jobs I ever had , because when you're CEO , you're the boss , you get to do what you want to do and you own it . If you're CEO , you're the boss , you get to do what you want to do and you own it . If you're right , you own it . You're wrong , you own it . And life's pretty simple .

When you're as a CEO who's developing an imminent number two to take over , you're really always trying to get them to do it and do it in a way you can live with . And bob bob's his own man and quite talented fella and his way of doing .

It wasn't always what I , what I would have , what I would have done , I told him and we were very good friends and colleagues and um , but it was really hard to kind of be that mentor . Uh , because at the end of the day , in a public company you know you're still responsible . So it was a little more stressful than I thought at the time .

But it all worked out great , passed the baton to Bob in 18 months and he went on to have a great exit with Antares Pharma . It was acquired a couple of years ago for a couple of billions . So it was all good and very proud of him . He did a great job . So when I left Antares I said , okay , I'm done with the CEO thing .

Enough is enough , I'm going to find something that really is what I want to do without being a public company CEO . So I ended up at the Brigham Brigham and Women's Hospital , harvard Med School . They brought me in to get their translational medicine accelerator off the ground .

They had gotten a big endowment to really fund translational medicine accelerator , really going from bench to bedside . And they said we want an entrepreneur like you who has drug and device development experience to mentor our faculty , teach them how to be entrepreneurs . And I thought , wow , this is cool .

I'll have my arms around the whole pipeline of Harvard Medical School . Imagine the faculty at the Brigham . I mean the best in the world , nobel laureates , et cetera , et cetera . I said this is crazy good and it was . It was absolutely magic . The faculty was incredibly appreciative . Even when my lesson was your baby's ugly , you need to kill it , fail fast .

They were still appreciative that . They learned a whole lot and I thought I was done . I was really very , very , very happy there and I got a call from a former colleague , a research physician , who said hey , hobbs , you have to come see my data . I'm curing metastatic prostate cancer .

And I said , buddy , I'm literally standing in the hallway at Dana-Farber and nobody's curing metastatic prostate cancer here . So how the heck are you doing that in Fort Lauderdale , of all places ? Heck , are you doing that in Fort Lauderdale , of all places ? So he said well , come down , I'll show you . So I did and he did .

He had developed , or helped to develop , a new method of immunotherapy that was showing incredible promise and in fact he had a case series where he was very successfully treating late-stage castrate-resistant prostate cancer patients who were hospice-bound , and getting complete responses Unheard of , including resolution of bone mets .

As I peeled that onion , it became clear that he had adapted his case series from another physician who I knew , who had trained him , who had over 400 cases at the time by the name of Jason Williams , who's the real pioneer of this sink teeth therapy . So went to Jason Williams , did a deep dive on his data .

Went to Jason Williams , did a deep dive on his data . Most of it was in lung and metastatic lung and breast combination product of a complex immunotherapeutic with a new device . And I said , wow , this is a massive breakthrough if it's real . It's , you know , it's anecdotal data . And oh boy , it sure's real .

It's , you know it's anecdotal data and oh boy , it sure looks real . So I brought in a team to really go through the data , including my old friend , chuck Link , who was a year behind me at the Air Force Academy . He didn't finish either .

He went on to med school in the middle of the Air Force Academy , but in the small world department , and Chuck's a medical oncologist , nci trained , nci fellow and an entrepreneur himself in immuno-oncology . He came in , peeled the onion and he said Eamon , this is the best thing I've ever seen . We need to figure out how to get this to patients .

And I said I'm thrilled to hear that , I'm all in . So we put together Synchromune and funded it and got a phase one trial in prostate . Some of the leadership , or every every leader we could hold still and it's just incredible data . We have an 85 percent in our valuable patients , which is 13 out of the out of the 15 in the trial at that time .

In our valuable patients , which is 13 out of the 15 in the trial at that time 85% overall response rate and five complete responses , which included complete resolution of bone mets . And you know , in immunotherapy when you get a deep , complete response like that , it's very often durable and after five years you years you can start to call that a cure .

Our longest patient out now is well over a year disease-free and we couldn't be more thrilled . We have another phase one trial with a different drug in metastatic lung and breast metastatic breast and we just had a . Well , I can't talk about that , but we're having great success there too . Really exciting . It's truly the best project I've ever been involved with .

It certainly has the potential to be most impactful in that there are millions of patients every year who can benefit from this therapy and it's just magic from this therapy . And it's just magic . I think it's worthwhile to talk about the complexity of the drug device combination , in that it's not just a drug device combination . And those are hard .

We all know that . I always say developing drugs is really hard . Developing new innovative devices is really hard . When you combine them , it's really really hard .

You know , the first thing to think about drug-device combinations are they are going to be harder , but if the juice is worth the squeeze , so what you know , we know how to get these over the finish line . You just need the resources to be able to do that , which can become quite significant .

So if the market's big enough and the unmet need is big enough , then you know it's still very viable and in this case that's the case , still very viable and in this case that's the case . So SyncD is a combination of a proprietary device that creates an in situ vaccine by doing oncolysis of a small part of one selected tumor .

We're not trying to ablate the tumor , not trying to kill it . We're just trying to rupture cell membranes in a preponderance of cells in a small part of the tumor , to release the cellular contents , which include the all-important antigens , tumor antigens which the immune system can use to build an immune response to that specific cancer .

So it's a personalized vaccine . And into the device . The second thing the device does is provide a conduit or a needle to infuse the drug , which is a multi-target immunotherapeutic comprised of three monoclonal antibody checkpoint blockade and one nucleotide , one oligonucleotide TLR9 agonist .

So we are hitting the immunosuppression with multiple targets , which is quite effective and been shown to be quite effective with systemic therapies , but prohibitively toxic and being highly immunostimulatory at the same time .

So the drug is doing a lot of things all at once , but the mechanism of action really is to synchronize hence the name Synchromune synchronize the location of the three things you need in order to get an activated and properly educated T cell , and that is you need the antigens , the tumor antigens , you need the immune system components to do their thing and

educate a T cell , and then you need the drug necessary to combat the highly immunosuppressive aspect of what makes cancer cancer and be highly immunostimulatory to force the interaction to take place . When you've synchronized the location so the antigens , the immune system and the drug , that's what the infusion does and the magic can happen in the tumor microenvironment .

But we think more likely the infusion washes the antigens and the drug out of the tumor microenvironment into the draining lymphatics where we all know have the highest concentration of immune system components in our bodies . So it's the perfect place to create the synchronization of location .

So think about this it's a brand new device that has absolutely no utility for anything . You don't want to lyse tissue in the body . You want to ablate it and a margin of healthy tissue around it to have a positive effect in focal tumor therapy . So lysing a small part of it doesn't do anything for anybody , except in our therapy .

You want to infuse a drug in relatively high volume through that conduit that's going to take the lytic debris and wash it out into the draining lymphatics and then you have a four-component large molecule co-formulation . Other than that , this is really easy , right ? Real simple . Yeah , real simple .

What did you know , going in , about how difficult a wall that was going to be to climb to go out and say , hey , you know , you've never seen this before , but you ought to give us a whole lot of money so we can keep moving this thing forward . And go to the regulatory authority and say , hey , you've never seen this before .

But give us all the green lights , man , because we're doing some special stuff here . What did you know going in ? And then , what did you learn as you lived it ?

So there was that challenge and at that time when we started the business , there was no precedent for a co-formulation of any two monoclonal antibody checkpoint inhibitors . Now there is . There's a PD-1 , lag-3 co-formulated product that has been FDA approved . So that certainly helps . But back then no .

So investors looked at this and they said you're doing what with what ? And so we would show them the anecdotal clinical data and say here's the signal that's got us so excited . And it's not well-controlled data , it's practice of medicine data and it's very , very hard to sift through . But the complete responses are there and they've been durable .

You know the pioneer , jason Williams . Dr Williams has patients out over a decade and you know this has got us really excited . But all of that aside , we know we need to develop in a very rational and well-controlled way a new drug and device , and we know how hard that is . But we've done this before .

We've assembled the best team to do this and we think the juice is worth the squeeze we have . We've assembled the best team to do this and we think the juice is worth the squeeze . The the investment community was was very incredulous .

They and you know , you just have to keep kissing frogs worth individuals , including ourselves , without any classic institutional sponsorship to get to the data we have today .

So it was a unique sort of investment pathway in that we convinced very smart high net worth investors but they also had the altruistic side of hey , they've done incredibly well and they wanted to invest in things that could really help people and this certainly checked those boxes off and they invested .

You know the institutions weren't at high net worth individuals it's as much about the jockey as it is the horse . So they invested in the team and Chuck Link and I , being serial entrepreneurs , had some credibility and we surrounded ourselves with an extremely credible , world-class team that the investors appreciated .

And then we brought in an independent board early on .

We call it a public company ready board to further validate that we weren't crazy and we're trying to keep our feet on the ground and our lead independent director is Doug Watson , the former CEO of Novartis , and he was the chairman of Dendreon , the first immunotherapy company to get approval in prostate cancer .

So an incredibly credible , seasoned big pharma executive . That added a tremendous amount of adult in the room supervision , as he always does in a very kind and gentle way , but when the Oracle speaks we all stop what we're doing and listen . For sure . We also have Norm Schwartz , the chairman and CEO of BioRat , a very , very large med tech company .

He was very passionate about cancer therapy development at a cancer therapy development . A public CEO who took the company his parents founded to over 15 billion in market cap and it's just a sharp dude .

And then Jeff Cleland , a serial entrepreneur in biotech who is a biomedical engineer , mit trained , and who is a biomedical engineer MIT trained and is on the executive committee of bio . So he brought just a wealth of entrepreneurial experience to the board . And then a physician by the name of Joe Maroon who's really a legend in big pharma .

He's been on many big pharma boards but also the former chair of neurosurgery at UPMC and trained most of the great neurosurgeons in the world . He's up there in age but looks like a young man and acts like a young man and he his incredible dna .

He's also the team doctor for steelers and and and and um , and super passionate about cancers and and , including the potential for this to ultimately go into gbms and other other brain malignancies . So , um , we have a really correct board and that helped with the investors a lot .

We're right in the middle , actually , of doing a crossover Series A , which will be institutional and will set us up for an IPO once the market for IPOs reappears , which sooner or later , it always does . So we're ready to go . We're out of it . We're all out of stuff . But there was nothing easy about this project , that's for sure . Funding was tough .

The scientific community was incredulous . The data looked too good to be true , which is an irony . You know , when your data is good , people challenge it . When it's too good , they're really challenging . Like you know , how could this possibly be ? And and I had the same reaction when I first saw it .

You've got to face some of that same sort of incredulous reaction from the people who you want on your team I mean board aside when it , when it , when it came time to build the Sync Immune team and put a staff together , how did , how did you go about doing that , given the fact that you know you've , you've got to have , obviously , biologics expertiseics

expertise , device drug delivery device expertise , and then the combination of those two things , limited pool to fish in , I'm sure , indeed ?

So it's a highly risky game , high risk , high reward game , and folks signing up for that have to be cut from that kind of cloth , have to have that entrepreneurial attitude and preference that they like the adrenaline , so to speak , of being on the edge , because it is the edge in reality . We try and mitigate as best we can .

Chuck and I founded the company and we brought our best and brightest from our former lives to the team and you know that that's incredibly helpful because you already know , you know they're known entities , you already have the rapport , you have the trust , you know their strengths and you know their , their developmental needs .

So managing them is is is less of a learning experience and more of a let's just get right to it . And and they , you know we're Chuck and I Chuck and I are a known entity to them as well , so you can really hit the ground running .

They were all very , very busy doing other things , so getting them took some salesmanship for sure , and as entrepreneurship always does . But we did assemble a really phenomenal team and the people you look for I mean ideally you would assemble a team where everybody has combination product experience . Everybody has both drug and device experience .

And the way I try and describe drug-device combination product development is a Venn diagram of three circles , and where these three circles converge is the new therapy . So drug-device combination product is really a new therapy .

So the three circles are the drug , the device and the procedure , the all-important procedure , because if the procedure doesn't go well , the drug and device aren't going to work . If the device doesn't work , the procedure and the drug are irrelevant , etc . Etc . The drug by itself doesn't work . So it's truly a Venn diagram .

So every decision the development team has to make has to be in the context of that Venn diagram , in that you can't just do what's best for the drug . It has to be what's best for the drug but also works for the device and the procedure . You can't do what's just best for the device .

It has to work for the drug and the procedure , et cetera , et cetera , work for the drug and the procedure , et cetera , et cetera Really challenging . So when you build the team you need expertise in all three of those circles , plus the convergence , the therapy . So how many of those people exist on the planet ? Very few .

So a , so a lot of time you you end up with people who are expertise in the drug but really have very limited , if any , experience in the other two circles . So you have to do a lot of education and uh , vice versa for the device , uh procedure team . Most device people have procedural experience because of the nature of devices .

Very few drug people have procedural experience because of the nature of drug delivery .

So , having spent decades in combination product company leadership , I have a canned presentation , educational presentation that I give to the team early on , that explains how it all comes together and why drug people are what and how they are , and why device people are what and how they are . So to distill it all down , the Venn diagram .

And then we go into well , what's the average very successful drug person ? What's their DNA like ? Well , they have a lot of degrees . They've got , you know , an MD , phd , mousd . They've got lots of letters after their name . And there's a reason for that .

The reason is what's most important in drug development by far is the quality of decision-making , because it's not an iterative process . Iteration is too expensive . So you really need people who are incredibly well versed in analyzing complex data and distilling it all down to a decision that at least has a good shot of not crashing and burning .

But again , most biotech companies fail because the hypothesis failed and that's with brilliant minds that have MD , phd , mou , sa all over it making phenomenally good decisions that turned out to not be correct . So tens of millions , if not hundreds of millions , of dollars go down the drain because your hypothesis didn't work and you can't iterate .

Now we look at the device world . In a device world , it's not about the quality of decision making , it's about the speed of decision making , because it's all about iteration , because iteration is cheap , it's way cheaper than time . So fail fast , fail fast , fail fast , learn , fail fast , keep going , keep going , keep going .

And that is the antithesis of a PhD or an MD or an MD-PhD . Think thought pattern . So when you put these very , very and if you look at the degrees in the device world , it's typically not a lot of not as many for sure advanced degrees , because it's more about do , do , do , do , do . You know , make those a lot of engineers , a lot of .

Let's do quick experiments and iterate . So when you put these very disparate thought patterns together into an organization that has to seamlessly work together in this Venn diagram , it's oil and water , unless you educate them right away that there's a reason why your colleague across the Venn diagram doesn't think like you do .

So once the you know , if left to themselves , if the drug people would look at the device people and say you guys are just frenetic , you just run around with no data , just doing crazy stuff , throwing it against the wall , see if it sticks , and then move on , move on . You know you give you give me heart palpitations just watching you do your thing .

You , you talk to the device people about the drug people and they say you know , you guys are like park statues . I'm surprised pigeons aren't landing on your thing . You talk to the device people about the drug people and they say you know you guys are like park statues , I'm surprised pigeons aren't landing on your shoulder . I don't ever see you move .

You're just sitting there thinking all the time and not doing anything . But once you educate them that there's a reason for that thinking , because if you took a device mentality and put it in pharmaceutical development or biotech development , you would crash and burn really fast because you just you can't iterate . It's tens of millions of dollars .

Every time you change anything You've got to be right . And if you take a drug person and put them in the device world , people will have to feel with them because they're not making decisions fast enough , they're not iterating , they're making really high quality , too slow decisions . So there's method to both .

That is absolutely valid and respecting that difference is the lesson of the plan . Is that respect your colleague , that they need to think like that and support them in that need to think that way . You don't think that way if you're in the device world looking at the drug world . You don't think that way .

If you're in the drug world looking at device , but understand it's a thing that needs to be and it isn't transferable and it works . They're all smart people . They go wow , I never thought about that . But gee , yeah , all smart people . They go wow , you know , I never thought about that . But gee , yeah , that makes sense .

And and yeah , yeah , yeah , ok , yeah , I'll stop bugging the vice president , stop bugging the direct people about getting you know . Why are you , aren't you guys done ?

I'm involved in that all day , every day , making sure everybody's aligned and the plans are in place . It's a symphony . You've got to conduct the orchestra because it's complex music for sure .

In the device world it's similar but more flexibility . Sometimes you can do it internally , sometimes you can't , but you know it truly is a lot of managing of very hyper specialized vendors that are doing the work of the very , very complex work and keeping them all aligned , because not any one of them has the whole picture . One of them has the whole picture .

The molecule CMC folks have no idea about devices , nor should they . The device folks have no idea about the CMC . It's coordinating it all and keeping the line is what the management team does day in , day out . And then we do have internal things that when we can and when it makes sense , you know , on just a regular kind of make-buy .

You know , do we internalize certain things ? Sure , we do , but vast majority is managing outside specialty vendors .

I am All right , a couple more questions , then we're going to need to wrap things up and probably schedule a part two and perhaps a part three and perhaps a part four , because you're one of those interviews , eamon , who , like you , make the job easy for the interviewer .

I asked one question and it's like winding you up and watching you go , which is great , yeah . So the third part of that Venn diagram . I'm a little bit curious about the procedural part , I guess .

What's the strategy , what are the plans for sort of clinical procedural application , given that we're talking about , you know , a unique device , a unique combination of therapeutics , a unique mechanism of action , multiple mechanistic elements to the drugs mechanism .

So just give me some , I guess , forward-looking statements around what the plan might be there to actually execute in the clinic , statements around what the plan might be there to actually execute in the clinic , let's say , beyond approval , beyond commercialization . How do we take this thing that no one's ever you know practitioners haven't seen it before either .

So to get a site up and running , in a prostate cancer trial , for instance , we need three PIs at every site , we need a urologist , we need an oncologist and we need an interventional radiologist . And the reason for that is depending on the approach taken to treat the patient either intraprostate or treating a MET .

The urologists are very skilled at treating prostates percutaneously . They do prostate biopsies all the time and brachytherapy and all kinds of things with transrectal ultrasound approach and transperineal access . So it's a home game for them . Once we teach them the procedural aspect of it , the urologist can certainly do that .

But if the patient doesn't have a prostate , just has metastatic disease , then the , the met , has to be a met has to be selected for each cycle of therapy , and that's typically ct guided . And that falls outside of the typical skill set for a urologist , because they just don't have any need to be doing that .

So we need the intervascular radiologist at that point , who ? That's a home game for them . They can access anything from anywhere with CT guidance or any other guidance and doing needle biopsies all the time . And then the oncologist is there to manage the complex post-op care that can be needed because of the immunotherapeutics .

We're blessed so far in the clinical development programs that the toxicities have been grade one and two and very low toxicities with really high efficacy , which is in itself a paradigm change and a bit unprecedented . But the oncologists are really the only ones with the skill set to manage immunotherapy , post-op and all the patient care required .

So we need those three PIs . So for every case we've got those three PIs there , and to varying degrees . So the urologist is there , the inter-restor radiologist is there and the oncologist is sort of hovering , you know , over the procedural aspect . Make sure they understand what's going on .

And in the room we have our own urologist , interventional radiologist , a med-surg , nurse , rt , potentially dual certified , who really is a jack-of-all-trades procedurally . And then we have an engineer who knows the equipment inside out in case there's a problem with the equipment . And of course the first case it's a C1 where we have the proctors really really helping .

You know very , very , very intimate in instructing step by step by step . So we're trying to get to the C1 , do one teach one scenario of procedural learning in medicine ? Yeah , so we keep the urologist , the inter-restoradiologist and the nurse and the engineer there until the clinical team's basically doing it repeatedly without any real intervention .

The urologist and the inter-restoratiologist then go to another site to get that up and running , but we leave the nurse and the engineer there permanently . They're there for every case as backup . So if anything goes wrong and there are , you know it's a busy place . You know these are typically academic medical centers and the team might change .

You know there may be a new , a new nurse or a new tech or a new , a new clinician who needs needs help . So there's a there's a reason for our folks to be there , one to recognize how well the team is trained and if there's swap outs , you know to be alert to that and then get whatever we need there .

But in clinical development it's critically important to realize going in that Murphy is a close family relative and Murphy's law is going to apply and what can go wrong will go wrong .

So you've got to be there for every last case when there's a procedure involved , you may be standing , you're hoping you're standing in the hallway board because the clinical team's just crushing it and that you know that's a great problem to have , but and that happens until it doesn't , and then you better be there and keep things going , because running the clinic ,

everything in these development programs is best accomplished by doing it right the first time , because the second time is incredibly expensive and the data you've generated poorly is now across the bear that you have to overcome with better data . You have to overcome with better data .

So the best way to deal with problems is to prevent them from happening by being very attentive all the way through . So once we get to commercialization though and I've done this many times in my career it's a similar situation , but we're not running clinical trials anymore .

These are practices , and it really comes down to see one , do one teach one , and the good news is that urologists , clinically , know this technique inside out . I mean , this is a meat and potatoes foundational procedure for them , same for the interventional radiologists .

A foundational procedure for them , same for the interventional radiologist , same for the oncologist . Managing immunotherapeutic toxicities is their bread and butter , so it should be fine .

And the reason there's such a disparate difference there is when you're developing a new therapy , the most important thing is developing the new therapy so patients can ultimately have broad access to it , and when you're treating a patient , the most important thing is that patient .

So it's a very different world when you get out into the commercial world and if they don't follow the protocol because it's in the best interest of the patient , well that's the practice of medicine and you know that's absolutely appropriate . That's forbidden in clinical development .

You got to stick to the protocol or have an amendment to the protocol because of a need . So you're really trying to do what's best to get it to millions of patients and that can often often , you know be a tough decision that the sponsor needs to be a part of .

So we're off to the races to that . Phase two trial will be registrational intent ultimately . So our clinical development pathways laid out . We've got a .

We plan to add a basket trial for the drug we're having such great early success with in uh in prostate cancer , the basket trial and other other malignancies , other cancers , and this follows the path that merck and bms took for optivo and keytruda to expand the indications with a basket trial and when you see signals you just go right to continue that trial to

registration . So we're on a very well-paid road there . In parallel we have another drug that we're pursuing for metastatic lung and breast and that's in phase one . We're very pleased with the progress there .

Haven't announced anything yet , it's early , but once that data is ready it'll go through a similar path that the prostate cancer did and hopefully we're ready for next year's ASCO with that drug candidate in lung and breast , if not sooner , and that'll take on its own development pathway . So busy , busy , busy .

Find that link in the show notes as well , and you'll also find a link to register for the BioExpo Live that was referenced at the beginning of this episode . We'll drop a fresh episode of the Business of Biotech on Monday morning , like we always do , and in the meantime , thanks for listening .