Drug Discoveries: Translation to disease management protocols for patients



welcome everybody again to an episode of the idea me show the show that profiles humans behind the really big ideas that shape our world inspire future creation and for all those that like really good stories I'm IRA pastor your health aging and longevity ambassador along for this ride and so for the last several shows we've been spending a lot of time at the different hierarchical levels of the disease and aging process from the genome to tissue level physiological networks to the microbiome even into the organisms external micro environment however exciting is all of these scientific discoveries we've been profiling are at the end of the day to have a beneficial impact on human health and disease and all the unmet medical needs we still facing us in 2019 it really boils down to one thing proper translation of these discoveries into registration 'el and commercializable interventions that clinicians can prescribe and patients can make part of their disease management protocols so today's guest who is joining us I'm extremely excited about clearly the the experts expert in doing translatable drug development the right way is dr. John la mattina with a PhD in organic chemistry John climb the ladder a Big Pharma to ultimately become president of Pfizer's global are in the organization where he managed a group of 13,000 scientists and professionals from across the United States Europe and Asia and for any of us that were in competing drug companies at the time sort of watching the blockbusters come off the line this is what we were dealing with lipitor viagra so loft zithromax celebrex diflucan the hits kept coming fast and furious and really turned Pfizer into what became of 50 billion dollar-plus mega farm organization is today after Pfizer John moved into venture capital as a senior partner at the pure tech venture group where he sits on the board of many different startups and development phase companies in biotech he's the author of several books including drug truths dispelling the myths of R&D and the recently pub devalued and distrusted in the pharmaceutical industry restore its broken image he's also routine contributes who will afford the magazine that being said John thanks so much for coming on the show today and joining us my pleasure definitely my pleasure so for for those outside of the farm industry that are unfamiliar with you I just I'd like to give you the floor just for a little bit and you know introduce yourself the sort of your background where you grew up how you ultimately got interested in science and the farm industry and ultimately how you made it to the top of what was arguably sort of the baddest rnd machine on the block in last couple decades I'm born and bred in Brooklyn New York a long time ago I always had an interest in science I was one of those kids who had chemistry said and didn't know what I was doing really when I was 9 or 10 years old but had fun with that eventually I know I'd like to pursue chemistry at it but I also wanna pursue chemistry in such a way that whatever I did could possibly be used for a purpose sounds egotistical but perhaps the benefit mankind so as I as I went through college and graduate school the postdoctoral work it was pretty clear to me that doing organic chemistry the actual making of the molecules and try to design that that biological activity was what I really want to do was really very exciting or frustrating work because they says you've probably told your listeners in the past you can have a great idea and come up with interesting hypotheses and develop a molecule that might actually test on hypotheses in humans if you're lucky get to people and get approved by the FDA and for every one comin you put into the development for a tiny pudding development one comes out the other end so it's and further it's a very time-consuming process anywhere from 10 to 15 years so you if you're somebody who likes instant gratification is not necessarily the field to go into but the great part of that was I got to work with brilliant scientists from different disciplines in any drug discovery program which is where I started if chemists biologists molecular biologists from the tableaus and people process chemists formulation scientists toxicologists etc although trying to get to the end goal drug benefit thousands of them millions of people across the room so what it works it's very exciting looking back on the industry now so you know I didn't around the industry for a while myself I think if I agree with me that even if we go back say 20 years it's a very different place than it is that's you know what's done very differently sin is today you know Big Pharma has transformed itself into mega Pharma you have many biotech companies of yesterday you know the Gili ads and the sell jeans which now you know you open the Forbes magazine and they you know they're in the top 20 pharma companies in the world you hear a lot about personalized medicine and orphan diseases and more targeted approaches but at the same time I'll read things about you know people in Wall Street saying well you know how they gonna keep up their growth with without blockbusters at the same time I have people on the other end of the sort of the pipe you know complaining about the so-called valley of death how it's gotten so broad and you know venture investors are investing later on because Big Pharma only once you know finish stuff and it's very hard to get a lot of the seed early-stage funding can you just give us your top line on sort of where you see things in 2019 both from sort of big pharma perspective and the venture perspective and sort of where a lot of this you might think is going though in the next a decade or so so a couple of things first of all it's interesting you read off some wonderful molecules that finds a market the 90s interestingly enough they're all small molecules if I you would ask me what the big changes are now with the most recent FDA approvals for the class of 2018 roughly half of those molecules are biologics that's more antibodies to therapies and even though there are the different things so if you had one thing first of all that's been a major change the type of medications people with that has really made a landmark change in and how companies are crafting their portfolio so when I was at Pfizer our portfolio in terms of research was largely in the areas on drugs diabetes drugs neuroscience drugs ecology group and an arthritis group what are leading players who will get Pfizer's portfolio now it's oncology rare diseases vaccines and in immunology complete turnaround in 20 years and what's driving that turnaround is a very interesting observation that you can make major breakthroughs for drugs but drugs medicines that really are meant for smaller populations orphan diseases but you have to really qualify orphan diseases cancer is that really one disease it's made up of dozen or so orphan disease and what's also happened is that companies have realized that you can get good pricing if you come up with a really good medication even though it might serve only 10,000 and so you touched a little bit about the future of being dependent on blockbusters I think the industry is going to do very well with with a portfolio that you know you're always gonna know sure nobody's going to turn to having an outsider's drug which would be a blockbuster category but there's sometimes there has been incredibly difficult but clearly people could generate a very distinguished portfolio and successful portfolio with drugs that may only treat 100,000 patients but that are priced well they won't be the lipitor speaking at close to thirteen billion dollars a year but there will be two or three billion dollar medication that however has and it's also resulted in the rise of a whole nother set of approvals you have to get approval from the FDA but now you also have to show the benefit of your medicines to payers that's companies because just because you have a new drug that can treat a condition where there's already a draw the drugs in the marketplace doesn't mean to say that a payer will willingly reimburse it patients in their health plans will have easy access to it great examples going on right now is in the bathro sclerosis area where statins are mentioned one of Lipitor ease and other stats have done very very well that now generic in their dirt-cheap there are companies now trying to come up with other agents that will lower LDL cholesterol the so-called bad cholesterol that perhaps could be additive to lipitor or be used in people who statins aren't well tolerated but the hurdles that these companies have to go what's tremendous not just with the FDA but for payers because a high dose of statin is still pretty cheap and you could name a percentage 70 80 90 percent of patients are well served with that just because something is new and may lower LDL cholesterol differently doesn't mean to say that the payer will clearly agree to part of a formula you have to prove to them that it has a benefit in addition to what statins and those kind of studies are expensive outcome studies where you compare your new therapy to existing therapy and basically you take people who already had a heart attack or a stroke and you and you randomized them to get either your drug or a standard therapy Lucido versus that there and you have and these studies will take five years and cost about a billion dollars and you have to show that your new therapy is performing better in reducing heart attacks and strokes then that's a whole new okay it's a bit of a winding answer to your no no it was great and I want to sort of continue along that path because as you brought up sort of the pharmaco economics of the system now and then also sort of the requirements from a regulatory perspective in terms of proving some of these these different types of outcomes then we dealt with in the past I want to sort of move into an article that you wrote about a month or so ago in Forbes which was entitled the challenges and bringing an anti-aging market where you basically highlight the fact that it's an area that you know while potentially very lucrative big pharma has shied away from it it could take a very long time you pay off his years away and you've highlighted some potential with sort of but the metformin study that may or may not be happening the article drove people in the longevity biotech space crazy some of them went nuts and I was standing there like and I'm on the fringes of that industry in a sense and say wait a second calm down you know number one Jon knows what he talks about and number two yeah as good as Science and Technology in the space maybe getting it still has to be be translatable could you just give some of your top-line thoughts on sort of the aging biotech space as it exists today and sort of your feelings as far as developing therapeutics for diseases of aging versus the core processes of aging first of all I just had like a 69th birthday if somebody comes up with that I found a youth drug man he'll be the first to take it I saw so I have a personal stake in the success of this area and I'll also say that there are excellent scientists doing great work looking at different mechanisms that can extend the life of circles and hopefully translate that into the life of animals and then humans but the science is very early and so yes you can you can extend the life of mice mention that for women with with mice by about 6 percent that's great but as others have pointed out mice are not humans and translating this work to humans is going to be difficult first of all so you can do great studies and animals but eventually you have to do a proof-of-concept study mules so you have to think about this a little bit so how do you do that if you had a real anti-aging drug you would put into people but what type of person would you pick you can't pick somebody who's 30 or 40 years old because how do you get it no it's extending their life they're way too young so you have to pick an elderly population constant let's use somebody like myself but it's 70 years old then you have to give the drug and you have to run study in comparison with placebo and you have to have people relatively healthy because the only could also be sick and you don't want to have people who have cancer or come down with cancer or prone to heart disease in your study so you have to try and take a somewhat of a fit population and you have to test them for a period of time and what you're measuring in such a study is living longer quite simply mitigating heart attacks or strokes or cancer or Alzheimer's or whatever in a patient population that quite frankly is going to get that anyway that's access point aging there run a study in 70 year olds perhaps and run a study for a long time and hope that you can see a difference and statistically speaking you'd probably have to run 10,000 patients in such a study or a period of time which costs a lot of money to do no I said so it's interesting you mentioned metformin metformin is an interesting diabetes drugs were on a mantra for 70 years and and these researchers found that in worms they can extend life 70% if you put them on that form and that's the aforementioned mice extended life 6% nobody knows how much Foreman works but certainly safe and so you can you can safely test the in people but the authors and the researchers here are having trouble raising the funds to do the study they think they do good to study with only 3,000 patients which i think is a reach you'd have to see a pretty profound effect of a drug with that many patients in order to be confirmed that it was working but they can't seem to raise the funds from places like the NIH I think they've had a study design for a while I think they call it ain't me but nobody's funding it just yet and I think that's the reason people are worried that how much this is gonna be very difficult to do it difficult to prove and so there's been a real hesitancy on people doing this and I don't know many big pharma companies involved they take enough long shots in their portfolios for things like Alzheimer's disease in other areas where something like this seems to be a bit of a hireling so it's it's not that I don't applaud the research I don't respect the research I don't think these are great scientists you use the great word before translation showing in people that these animal studies and translating it to a clinical study where it works is very very difficult to do now it's not impossible but some people are doing or are trying to see for example during flu season if you if you have a dream that you think is helping the aging process by helping the immune system then maybe if you had a flu season you took an elderly population which is susceptible to a team of flu that maybe you can reduce the incidence of such attacks during a winter and Eric some companies approaching it that way and it's not necessarily a longevity drug although will certainly save lives and I think that's very very important but the whole family youth concept I think right now is it's got a long way to go moving on the along those lines going from sort of the registration 'el dynamic to more of these sort of the legislative front now you know there's been a lot of activity in recent years both here in the US and abroad on different ways to sort of go about speeding up the development process or at least the delivery of development stage candidates to so-called no option patients obviously here in the US we you know pass the the right to try legislation though there's obviously a lot of debate whether that versus traditional expanded access is viable or not in Japan you have this conditional approval process for certain regenerative medicines phase two and then you know when reading about some really strange things you know about a year and a half ago Merck announced this deal with the government of China basically you know they set up this location as Hainan Island which is somewhere south of hong kong east of vietnam where basically you as a cancer patient could go if you have a cancer that kate ruda is not approved for you can go on a nice vacation and warm weather nice beaches and everything and try it so very interesting to see you know one of the largest drug companies the world sort of getting their feet into medical tourism which is always sort of seen as somewhat of a niche what do you think about some of these models are they do they have legs to them are they here to stay what's your opinion all this the earlier part of your question interestingly enough Scott Gartley who I thought was a terrific terrific FDA Commissioner mm-hmm I don't know so as soon as if I've got a back of a friend I thought was very progressive and he's used been working with the FDA on behalf of patients who are suffering for diseases from diseases there are no treatments and he has been very progressive in trying to speed the process of taking these companies obviously after on clinical trials but you might have a disease for where all the markers of the disease are being benefited by by the drug but you haven't proven yet that it cured or the progression of that drug that I'm thinking of muscular dystrophy as a specific example and and he's gone he's had the FDA look at these things and say look we know it's safe we've got a really good safety data early indications are that the compound may be working but there's no guarantee but these patients are in desperate need we're going to give a provisional approval for this drug keeping in mind that we want the drug sponsor to maintain their that you know studies and follow things closely and continually pull it back to us on the ongoing clinical trials but while our patients in this situation to have access to this drug now keep in mind there's some some hurdles they put there this has to be something where there's no other treatments people are failing and they need they're desperate situation that wouldn't be the case for drug again or lowering bad cholesterol because there are plenty of things out there in the FDA before so so I think that's a very progressive way because I think what will happen is some of these drugs will pan out and be by saving the life changing for patients who don't want choices and others won't and they'll end up being discontinued but I think that's a risk benefit that a lot of these patients are more than and it boggled about being willing to take now I will say that however and I'm a pro pharma biopharm guy there have been moves by certain opinion leaders that have said well the FDA should just be measuring drugs based on safety and then let's see what happens in the clinic and I think that would be a disaster I give you a graded potential example and that was in the autonomous area Eli Lilly had murdered for that matter as well had very interesting drugs that act by a defined mechanism that were believed to have the potentially reverse product in the brains of Alzheimer's patients and as the plaque in one's brains that's believed to cause all of the symptoms and anterior ation of the brain and in fact in they went into patients and studying early stuff so that they were actually loving the protein that had produced this these blocks of the brain in a scenario I just described where you'd be a little more relaxed the FDA could have given them convention conditional approval and I can tell you that millions of people would have would have come anybody without subversive film history also sort of trying to take this drug and then when they ran the multi year very expensive long studies these drugs didn't work and why didn't they work well nobody seemed to know they think they first looked the patients with severe disease that work they they went to moderate disease etc but it just it just failed I think you have to really think through various methods that or people in need and make sure that that you're not exposing too many people to something that really will and so I think each case and you go by a case-by-case situation finally that the last peel of the onion that you gave me birth in Southeast Asia it's interesting I wasn't aware of that some of us so you tell me a little bit on that one it's interesting that they've gone to China China's agreed to this it's not as if you're taking the drug that's improved cotrona there's a marvelous Brotherhood listeners not aware of it up regulates one's immune system to help fight cancer and it's in its but it doesn't work in everyone it doesn't work in certain type of cancers and this took me to learn why but certainly it's a drug with a track record of success the fact that the China government was willing to take the rotor says look we're willing to take people with them I'm assuming 1/5 of the conventional therapies and have them take two days I guess somewhat enlightened and unusual and I hope it can pan out certainly the Merc will be able to study many patients and you have to remember also that big makeup of Chinese is different from Westerners and other genetically diverse people and so you may get a different profile in Chinese patients that you might in watch the Patience's similar cases to be true to something so it's a tremendous opportunity to learn a lot about a drug proven drunk with it where the safety profile is very well known and learn from it so it'll be interest to see how that how that works in yeah I really doing that would be very interesting I promise you only one more multi-part question and then it will get the wrap-up going back to something that we touched on earlier when you brought up the sort of the transition from small molecules to more complex biologics gene therapy cell therapies things this nature one thing in recent years we've seen more of is what I refer to as untraditional pharmaceutical entities or weird weird products that some companies are beginning to develop I talked about for instance in my I was I was employed many years ago by GSK and a couple years ago they put a 750 million dollars into something called electro suit of goals hoping at some point I guess to get the drug out of the equation and use electricity and other signals biophysical signals or what have you as the drug itself and then I also think about some of us are the microbiome stuff that's going on where the the drug is you know I think some of them a pure tech might be invest in Smith stuff but you know a cocktail of bacteria or microorganisms or basically the drug looks very different than the little pill the noir Vasco whenever I take from from my local CBS looks to today it is two part question number one based on your experience with regulators are they getting better at reviewing and approving this type of stuff that they don't usually have experience with or is there a very is there still a long time frame that exists between when and the FDA for instance writes up a a guidance on how something should be done and then how they ultimately approve these things and number two second part a question before we talking about metformin and you brought up the fact that you know after 70 plus years you know people still don't really know about mechanism of action but you know thinking back to my big pharma days everyone was always so concerned about mechanism of action but some of this new stuff you know it's gonna be hard to say how an electrical shock or how a little group of bacteria you know what the mechanism of action of this stuff is is this a problem is it not are we moving away from mechanism action and moving more to mode being as important sorry that was a long-winded question but I really would love to hear your thoughts on these she look and I'm getting UCLA the crushing sadness is working out very well first of all before answering I want to give the audience complete transparency at pure tech we go into very nascent ideas and then we start companies if there's something you think behind the ideas and so I'm going to answer a part of your question using two pure tech examples what other companies we've formed is called Achille it's based on technology that came out of the University of California at San Francisco professor Adam Vasilis lab and it it's use of video games to help cognition disorders and you know it's not like playing Warcraft or whatever the games are but rather it's based on some segments of neuroscience principles trying to focus on one task while other tasks are are coming into play and the gazillion lab the marvelous work in looking at improving brain plasticity for a lack of a lack of a better term well we got involved with Achille in this whole technology and this is not a pill obviously it's a it's a video game but it's something that we actually went to the FDA and said we think this has a role in helping with a attention deficit disorder ADHD and the FDA's had fine we would hear on a clinical trial looking at these parameters which we've done and in the Royal way I Kelly has done and in fact we got very exciting results that show that the effect we're getting on standardized trial a standard on his measurements that the FDA has helped establish for ADHD we're getting as good an effect as you would get with the medications that are out there so hey that's pretty exciting I think because it offers an alternative to people who don't necessarily want to take a drug with the attendant side effects that they have on the drug that I saw I'm not bad-mouthing industry but I think you six-year-old comes home from school the teacher says he says HD ADHD and you're given the choice need to fill in a video game you may pick the video an answer to a question on how the FDA is handling these things they seem very open to new therapies new ways of approaching disease their key is always safety safety first and an ephah ski efficacy that's real efficacy particularly in areas with a very familiar you mentioned the microbiome again we started I think one of the leading microbiome companies and here we are looking and we have again started a great partnership with researchers in Tokyo and found that and people with various disorders let's say inflammatory bowel disease are missing certain bacteria and their microbiome and we have found in animal models and another one in clinical studies to prove it that if you can replenish these bacteria you restore the be gut to health that's pretty exciting now again this is early days the FDA while approving clinical trials in this area and has said the kind of things they'd like to see in an approval package how's it gone through the process yet but we're confident that again if we show it's safe and we show it's effective they're not going to say what Lissa's different we don't know what to do they will treat it like any other potential therapy way so I think I think the agency is learning the industry is learning doctors are learning and hopefully we'll all get to a point whether we can benefit people in new ways wonderful and I look for in fly I look forward to my son well he's a THD but he plays a lot of video games there you go therapeutic at some point the wrap-up question it has nothing to do with the pharmaceuticals or science anything like that it's what we call the science fixing question I'm giving you dr. John la mattina a chance to travel in my time machine anywhere to talk to any historical person you would like to Jonas Salk Einstein Edison you go to the future if you want and talk to your your great-great-great grandchildren take a couple minutes with this one if you need to but where do you got de la mattina want to travel and what do you want to talk about with that person when you meet them oh boy this is probably not an answer you're expecting I'd like to see a few things I would like to see one something somebody figured out the way to treat Alzheimer's disease I think I'm not worried about cancer treatments cancer is a horrible disease which is out there now so much is coming on board in within ten years maybe it's already happening now with it but within a decade I think any cancer that's diagnosed and not able to be treated surgically will be treated with a cocktail of drugs something to up regulate your immune system something specific for that type of to buttocks private net to and I saw the stuff is already happening so I think that's that's reality I don't think that's science fiction but Alzheimer's boy I don't know I don't know and as the baby boomer generation gets older we're going to have more and more examples of this is gonna drive health care costs dramatically it's going to be a real problem that we're all gonna have to face up to and the fact that we're doing other things for example like making cancer a chronic disease and art disease better and hopefully people stop smoking and we get around that the alcohol this is going to be more more people around Cyrus disease it's just the fact it's a disease of Aging and you didn't see it as much twenty years ago because people that live those long as they're looking down so that's a new problem and that's something I worry about boy if I'm going to finish and find out that we've reversed these obesity trends that would be that would be nice what it's so scary and I would encourage our listeners to go on the CDC website CDC gov and look at the patterns they have these wonderful maps that show the fattening of America state-by-state they're just a map the United States color coding and you see how each state on a yearly basis more and more people are increasingly getting obese to the para there are states in this country where close to 40% of the population is defined as being obese I think that's a BMI of over 30 and the attendant diseases that come with that in fact they also have maps to show that there's a five year lag time but a type 2 diabetes also increases in those same across the country but particularly in those states where oh this is increased Italian is unbelievable and type 2 diabetes leads to heart attacks and strokes and leads to blindness and kidney disease and there was a Woody Allen movie and cigarettes in cigarettes I'd like to come back and see that my great-grandchildren really all these things were things of the past and also he was treatable and cancer was treatable but people were living house deal I'm still into their early hundreds and hundred and ten was the general rich in the table lives much longer so that would be my science fiction wonderful wonderful appreciate that very much and I'm in the same basket is healing if we can make this better for my kids and their kids I'll be happy and that's one of the reasons I hang around in this stressful industry for so long John it's it's really been you know an honor having you here really thanks so much once again for everybody listening dr. John la mattina former president of Pfizer global R&D venture partner at pure tech ventures gobias book so on Amazon drug truce dispelling the myths of R&D and devalued in this trust that can the pharmaceutical industry restore its broken image read his column in Forbes magazine just a major font of knowledge for this industry where it's been where it's going and there's just you know thank you so much again for joining today you

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