Latest / Lab to Lives / Creating virtuous cycles in drug development with Rob Freishtat

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Creating virtuous cycles in drug development with Rob Freishtat · Lab to Lives

• 0:18
  Speaker 1: Welcome to another episode of Transformation in Trials.
• 0:21
  Speaker 1: I'm your host, ivana Rosendahl.
• 0:23
  Speaker 1: In this podcast, we explore how clinical trials are currently transforming so we can identify trends that can be further accelerated.
• 0:30
  Speaker 1: We want to ensure that no patient has to wait for treatment and we get drugs to them as quickly as possible.
• 0:36
  Speaker 1: Welcome to another episode of Transformation in Trials.
• 0:45
  Speaker 1: Today we're going to focus on the topic of creating virtual cycles in drug development, and with me in the studio I have Rob Freistadt.
• 0:54
  Speaker 1: Hello, rob.
• 0:55
  Speaker 2: Good morning.
• 0:56
  Speaker 2: It's great to see you, ivana, great to be with you.
• 1:00
  Speaker 1: Likewise, I am very excited about our conversation.
• 1:02
  Speaker 1: Rob, could you tell us a little bit more about yourself?
• 1:07
  Speaker 2: Sure, I am the president of a rare disease clinical trials company called Uncommon Cures, and a recovering physician scientist Did the whole academic thing for 25 years and now trying to have an impact in a slightly different way.
• 1:28
  Speaker 1: That's awesome, and we're going to get more into your background a little bit later, but for now just to set the stage for our listeners.
• 1:35
  Speaker 1: Can you tell us more about what are the current market dynamics that creates less and less funding for research in rare diseases.
• 1:42
  Speaker 2: that creates less and less funding for research in rare diseases.
• 1:45
  Speaker 2: Yeah, so obviously there's a lot of uncertainty in the market now.
• 1:50
  Speaker 2: I mean, there's been uncertainty for years, but investors don't like unpredictability, they don't like uncertainty, as I'm sure you know.
• 2:02
  Speaker 2: And so biotech investment has been sluggish, although it's sluggish even coming after an aggressive investment period during COVID.
• 2:12
  Speaker 2: It really slowed down and then it seemed like all the dollars were going into anything with AI in it, which is probably true, which is probably true and the expected uptick in biotech investment has been slower than we'd all hoped, and in part that's because of, you know, factors related to payer pushback on, you know, more expensive drugs.
• 2:43
  Speaker 2: So there's unpredictability around compensation on the back end or return on investment.
• 2:51
  Speaker 2: And then the changes happening in the federal government now post-election I'm not gonna pass judgment on whether they're good or bad.
• 3:00
  Speaker 2: They just provide a lot of uncertainty around interactions with the FDA.
• 3:09
  Speaker 2: And what's the speed at which, you know a lean down, slimmed down FDA staff is going to be able to respond to, you know, various different interaction requests, and so anything that makes the path to approval and to the commercialization more unpredictable is just going to put a damper on investments, and we're seeing that frankly with our smaller clients for sure have that, but they're talking to a different group of investors than, say, a big client with multiple assets at the commercial stage.
• 3:48
  Speaker 2: You know their investors are nervous also Different investors than somebody who would invest in two guys and a drug.
• 3:57
  Speaker 2: So everybody's pretty nervous and until the uncertainty abates to some degree, I think it's going to be a challenging time.
• 4:07
  Speaker 2: That said, the science is phenomenal.
• 4:11
  Speaker 2: It's just connecting the funders and the science in an effective, efficient way.
• 4:20
  Speaker 2: That's the challenge right now is really that's the challenge right now.
• 4:24
  Speaker 1: Yeah, I was reading an article this morning from the Economist where they were trying to analyze the volatility in the biotech stock prices.
• 4:34
  Speaker 1: Where some smaller biotechs have jumped up a lot in recent days, others have fallen.
• 4:41
  Speaker 1: The conclusion of the article was basically we're not sure what's happening.
• 4:48
  Speaker 2: Yeah, it's probably more case by case than market wide.
• 4:52
  Speaker 2: There's probably some smaller biotechs that have strong data and I mean, if you're a biotech investor, maybe that's where you're shifting your money, but I'm guessing I have no information that would make me think that's correct or false.
• 5:09
  Speaker 1: No, it's also like the long lead time for drugs.
• 5:12
  Speaker 1: One of my friends in Copenhagen has been working on a molecule for the past decade and now they're finally entering clinical stage.
• 5:20
  Speaker 1: And their company.
• 5:22
  Speaker 1: Its valuation is taking off, but the truth is it has nothing to do with the current market dynamics.
• 5:27
  Speaker 1: It's like it's the past 10 years of research that's making the big difference.
• 5:31
  Speaker 2: Correct.
• 5:31
  Speaker 2: And you know, like I said, the science is really good.
• 5:35
  Speaker 2: There's no shortage of investment opportunities.
• 5:38
  Speaker 2: I think investors are just skittish right now, for good reason, are just skittish right now for good reason.
• 5:50
  Speaker 2: And you know, there's so much good science that it's a shame because a lot of these companies are going to go out of business.
• 5:53
  Speaker 2: They're not going to get the investment they need or they're going to struggle for years cobbling together this, that or the other.
• 5:59
  Speaker 2: And it's a shame because ultimately, there's patience at the end of that right.
• 6:04
  Speaker 2: You know, that's why it's all happening.
• 6:07
  Speaker 2: And I do think that, in general, good science with a good management team and the right indication, is always going to be, or almost always going to be, a good bet.
• 6:19
  Speaker 2: Yeah Right, yeah Right.
• 6:22
  Speaker 2: And and so the fun, if the fundamentals are good, the the market matters less.
• 6:30
  Speaker 2: Right, because there's always going to be new drugs that are going to get approved, and if there's an unmet need, they're going to fill that need and somebody is going to pay for it, and at the end of the day, a lot of this other stuff is just noise.
• 6:46
  Speaker 2: And so, again, good fundamentals make for a good investment.
• 6:50
  Speaker 1: Yeah, I love that, and it's also just for everyone who is looking a lot at the market right now.
• 6:55
  Speaker 1: Let's focus on the science.
• 6:57
  Speaker 1: Let's focus on good leadership.
• 7:00
  Speaker 2: Yeah, and I think in these uncertain times that's actually the best approach to control the things.
• 7:05
  Speaker 2: You can control everything else, I mean look, it's there's.
• 7:10
  Speaker 2: There's ebbs and flows to all of this, and you know there's.
• 7:14
  Speaker 2: There's no time.
• 7:15
  Speaker 2: That's quiet, right, it's all.
• 7:17
  Speaker 2: There's always unpredictability.
• 7:19
  Speaker 2: It just you know.
• 7:21
  Speaker 2: Maybe it just feels a little more chaotic right now.
• 7:23
  Speaker 2: It just you know.
• 7:24
  Speaker 2: Maybe it just feels a little more chaotic right now.
• 7:27
  Speaker 2: But again, if the fundamentals are good, you know, the one thing we can be sure of is when these drugs that are looking for early stage investment, or maybe they're in phase one, phase two the one thing we can be sure of is when they do reach the market, it will be different than it is today.
• 7:40
  Speaker 1: Yes, that we know for sure.
• 7:43
  Speaker 2: Because I mean two years, three years, however long it takes, whatever it is, it will be different.
• 7:48
  Speaker 2: That's the change is the only constant right.
• 7:51
  Speaker 1: Yeah, yeah.
• 7:52
  Speaker 1: Well, it's like this unpredictability.
• 7:55
  Speaker 1: I know that you and I have both shared a passion for trying to simplify the way that we bring drugs to market.
• 8:06
  Speaker 1: You mentioned during a pre-call that you had embarked on creating a detailed overview of the process for getting a drug approved.
• 8:14
  Speaker 1: I'm curious to learn more about what did you learn during that process and what might have surprised you.
• 8:22
  Speaker 2: Yeah, so really, when we were starting the company and I mentioned this to you, you know we looked at the entire drug development pathway.
• 8:32
  Speaker 2: You know everything that, everything that takes place, each events and what processes underlie those events I mean, the engineers in your audience will probably love this, because it's very much an engineering approach and then breaking each process into its microprocesses and you know, and then evaluating each one for whether it adds value or whether it's regulatory, regulatorily required, and it turns out that a lot of the things we do in drug development are neither they don't add value and they're not required.
• 9:08
  Speaker 2: And so then the question becomes are they just wasting time, money, et cetera?
• 9:15
  Speaker 2: And it's not surprising.
• 9:17
  Speaker 2: You know it's the same process we've had for decades now in this country, in the US and, frankly, elsewhere in the world.
• 9:24
  Speaker 2: And you know, if there's anything we know about processes, we almost never, you know, take things away.
• 9:30
  Speaker 2: We always add, we slap Band-Aids all over the place until you've got this giant ball and you don't even know what it looks like in the middle, what the core is, and that's essentially what clinical development has become.
• 9:41
  Speaker 2: There's just all these appendages on it that don't need to be there.
• 9:47
  Speaker 2: So you know, in our analysis, when we got rid of those things, those extras, and put it back together into a streamlined process, what we found is that, you know, really only about a third of the things that we do on average actually are rowing the boat in the right direction.
• 10:08
  Speaker 2: The other stuff is superfluous.
• 10:11
  Speaker 2: And you know maybe some folks won't be happy with that, but you know, if we're looking at the process for an average drug to get through the FDA for rare disease, you know it takes longer than a regular drug and it costs almost as much for a common indication and you know, a lot of that is just extras.
• 10:35
  Speaker 2: That are maybe things that we do.
• 10:37
  Speaker 2: They're inefficiencies that when you've got a common drug they don't matter as much, because often for common drugs there's other drugs out there.
• 10:47
  Speaker 2: It's just here's another one In rare disease it's often there's no drug for these patients.
• 10:54
  Speaker 2: So anything that adds time adds cost that ultimately has to be borne by the payers on the back end or the patients.
• 11:03
  Speaker 2: And time, in this case, is lives right Because there is no drug right.
• 11:11
  Speaker 2: So it's either nothing or this new thing, and so the faster we get to the point where we have an answer, the more efficiently we get to that point.
• 11:20
  Speaker 2: It's good for everybody.
• 11:22
  Speaker 2: It's good for the sponsor because they're getting more exclusive time on patent.
• 11:27
  Speaker 2: It's good for the patients because they're getting a drug that could make them better or improve their quality of life where they had nothing before, and so that's a win-win.
• 11:39
  Speaker 2: And that's pretty rare in this day and age.
• 11:42
  Speaker 1: Absolutely.
• 11:43
  Speaker 1: I am curious how did these two-thirds of process emerged?
• 11:49
  Speaker 1: Is it because this is just how we've done things?
• 11:53
  Speaker 1: We learn from others who have been doing them, without necessarily applying critical thinking?
• 11:57
  Speaker 1: How did we get into such an ineffective state?
• 12:02
  Speaker 2: So I would say that the bulk of them are exactly what you just referred to.
• 12:06
  Speaker 2: It's just well, that's how we've always done it Right, and so it.
• 12:10
  Speaker 2: In some cases, there are things that may be applied to or that are fine for a common disease, but not so for a rare disease, and sometimes it's just administrative bloat.
• 12:23
  Speaker 2: You know it's.
• 12:25
  Speaker 2: You know gosh well.
• 12:26
  Speaker 2: You know, somewhere back in the history of somebody's career, a patient had this bad reaction and so we're going to do this, even though it's not applicable to this drug or any other situation.
• 12:39
  Speaker 2: You know, they, they put it, they put something in place, and maybe it was worthwhile, maybe it wasn't at the time, but then everybody.
• 12:47
  Speaker 2: But it never goes away, right, it just keeps happening and it's like oh well, we need these.
• 12:50
  Speaker 2: You know we need 400 SOPs for the protocol and we need an SOP on SOPs and an SOP on SOPs, on SOPs, you know it.
• 13:00
  Speaker 2: There's just layers of things that are not adding value, and I think a lot of it is just legacy.
• 13:07
  Speaker 2: It's things that well, we've always done it that way.
• 13:10
  Speaker 2: Why would we change?
• 13:11
  Speaker 2: If you're a middle person or a lower person in a big organization, you know you're not likely to get fired for doing things the way they've always been done.
• 13:22
  Speaker 2: Yeah, yeah, for doing things the way they've always been done.
• 13:25
  Speaker 2: Yeah, yeah, you're right, it's a system that reduces.
• 13:26
  Speaker 2: You know, research, clinical research, by its nature is risky.
• 13:30
  Speaker 2: There's always going to be risk, and nobody wants to hurt a patient, right, and so we want to be as risk averse as we can be, but at a certain point it impedes progress.
• 13:42
  Speaker 1: It's a kind of almost magical thinking.
• 13:45
  Speaker 1: This is the ritual that we do to conduct a clinical trial, and we're not sure which parts of it actually do the trick, but these are the processes that we have followed.
• 13:53
  Speaker 1: I love that.
• 13:55
  Speaker 2: I love that.
• 13:55
  Speaker 2: It is a ritual in a lot of ways.
• 13:57
  Speaker 2: That's exactly what it is.
• 14:00
  Speaker 1: And you're right, we are very risk averse, for good reason no-transcript?
• 14:12
  Speaker 2: Yeah, absolutely, and so you know, some of what we do is is engage the patients in those discussions Right, because ultimately they're the ones taking the risk and, depending on the disease and we've seen this in the US and other countries around the world during approval processes, where the patients are like we understand the risk and we still want the drug, we understand the risk and we still want the drug right, and in many ways it's not up to us to say for a patient or patient group you know we, we don't want you to take that risk.
• 14:47
  Speaker 2: You know that's a very paternalistic approach and you know these patients have agency and they, they can choose.
• 14:56
  Speaker 2: I mean, we want to de-risk the process as much as possible.
• 15:00
  Speaker 2: We don't want to expose anybody to unnecessary risk or unknown risk.
• 15:03
  Speaker 2: But ultimately the person signing the consent form is the patient, the person taking the drug is the patient and they have a say, absolutely, and it is for their benefit.
• 15:19
  Speaker 1: And these are people who make big life decisions in all other regards, so of course they can also make a decision for what's best for their health.
• 15:27
  Speaker 2: Yeah, and it's interesting, and the FDA and the regulatory agencies are actually far more progressive on this kind of thing than the sponsors.
• 15:37
  Speaker 2: The sponsors are very, you know, they have their, they have the way they do, they have their rituals, like you said, and that's the way they go and they think the FDA is at least as conservative as they are and in many cases that's not true.
• 15:52
  Speaker 2: The FDA has has evolved in its thinking as a whole and it's hard to say with all the changes that are going on right now.
• 16:01
  Speaker 2: I mean I just don't know how thinking is going to change, if at all.
• 16:06
  Speaker 2: But in general they want to see, you know, these treatments get to patients right and you know not to sacrifice safety.
• 16:16
  Speaker 2: But you know, recognizing that the patient has a say in selecting outcomes.
• 16:21
  Speaker 2: You know, I mean outcomes in clinical trials classically were always chosen by the sponsor, by the investigator, and never by the patient.
• 16:31
  Speaker 2: But does the outcome matter to the patient?
• 16:34
  Speaker 2: Probably does you know it matters if it.
• 16:36
  Speaker 2: You know, I don't care about that.
• 16:39
  Speaker 2: I want this.
• 16:39
  Speaker 2: You know this is what matters to me.
• 16:41
  Speaker 2: You know I love that.
• 16:42
  Speaker 2: We have a.
• 16:43
  Speaker 2: We had a patient in a trial whose sole goal of the trial not that this was an acceptable outcome for approval, but the sole goal of the trial was this patient wanted to be able to safely eat a steak.
• 16:54
  Speaker 2: Was this patient wanted to be able to safely eat a steak.
• 16:56
  Speaker 2: I love that.
• 16:56
  Speaker 2: So you know, which is when you take a step back and stop chuckling at it.
• 17:02
  Speaker 2: It's actually it's illustrative of the point you know.
• 17:07
  Speaker 2: But you know, what matters to me is whether you know this blood marker goes up or down as an investigator, but as a patient, he just wants to eat a steak.
• 17:19
  Speaker 1: Yeah, yeah.
• 17:21
  Speaker 2: And who can argue with that?
• 17:23
  Speaker 2: Or maybe a vegetarian, but he wants to eat a steak.
• 17:28
  Speaker 1: That's a great example, yeah, and for the individual patients, I can definitely see that there is a difference between having an increase in a biomarker, the individual patients I can definitely see that there is a difference between having an increase in a biomarker or the actual ability to do something that you couldn't have done before.
• 17:45
  Speaker 2: Right, and these things don't have to be mutually exclusive.
• 17:48
  Speaker 2: We can look at study data in multiple ways, and we can look at outcomes that matter to patients and outcomes that matter to scientists, physicians, prescribers, whoever.
• 18:01
  Speaker 1: Um, they don't have to be mutually exclusive, but, um, we've often treated it that way yeah, well, another thing we uh discussed in the pre-call that I have been thinking quite a lot about since is that you mentioned that drug development companies do not always plan for the success of their drug.
• 18:23
  Speaker 1: Why is that, and what would planning for success actually mean?
• 18:30
  Speaker 2: Yeah, so let's define that and then take a step back.
• 18:33
  Speaker 2: So you know, we encourage companies to think about, no matter what stage they're at, is what does commercialization look like?
• 18:43
  Speaker 2: Mm-hmm, you know if you're going for a pediatric indication, is your drug a pill or a liquid?
• 18:51
  Speaker 1: Yeah.
• 18:52
  Speaker 2: Right, and that's maybe an oversimplification, but you know it's an example of of the kind of decisions that have to be made in order to get the drug to patients in the commercial stage.
• 19:05
  Speaker 2: But the the the step back that we encourage people to take is to think about those things when those decisions need to be made.
• 19:15
  Speaker 2: So we find that companies will often think of preclinical phase one, phase two, phase three as islands and they're going to jump from one island to the next island and they don't think about the next island until they finished the island they're on.
• 19:35
  Speaker 2: And while that certainly can work, it ends up causing companies to go down some dead ends or have to redo things because they haven't thought through how a decision they make today affects the decision they have to make two years from now.
• 19:56
  Speaker 2: Decision they make today affects the decision they have to make two years from now.
• 20:01
  Speaker 2: And I totally get it because you know you're, if you're a startup biotech, you're getting funding for specific milestones and it's survival.
• 20:09
  Speaker 2: It's you know, maslow's hierarchy of needs right, it's everything.
• 20:13
  Speaker 2: Every decision you make is existential and you know you're just trying to get to the next funding and not really.
• 20:22
  Speaker 2: You don't have the bandwidth really to think about these things.
• 20:25
  Speaker 2: That are two, three, four steps down the road.
• 20:28
  Speaker 2: So we but we encourage people to do that, to think about those things, so as to avoid rework that ends up naturally happening.
• 20:39
  Speaker 2: So, yeah, so commercialization is important, even when you're in your non-clinical data generating phase.
• 20:47
  Speaker 2: What is this going to look like?
• 20:49
  Speaker 2: What's your formulation.
• 20:50
  Speaker 2: Are you going to have to go back and reformulate?
• 20:53
  Speaker 2: Maybe that's the right choice, because you need the non-clinical or the preclinical data to get to enough funding to be able to reformulate.
• 21:02
  Speaker 2: There's a lot of practical decisions, but you have to make those decisions as a continuum and accept that the decisions you make today are going to affect everything down the line.
• 21:15
  Speaker 1: There seems to be a scarcity of people with the end-to-end experience from a drug.
• 21:22
  Speaker 1: At least many of the early stage biotechs that I get to meet it's more like heavy experience on the science side and almost never any experience on the commercial life sciences side of things.
• 21:36
  Speaker 1: So it must be hard to find that expertise to bring into those early stages.
• 21:42
  Speaker 2: Well.
• 21:43
  Speaker 2: So I think it's a philosophical question that ultimately becomes a practical one.
• 21:46
  Speaker 2: So you know, at the early stage of a company, the decisions that are being made are often very scientific.
• 21:54
  Speaker 2: You know you're making business decisions too, and some scientists are better at that than others.
• 21:59
  Speaker 2: You know you're making business decisions too, and some scientists are better at that than others.
• 22:03
  Speaker 2: You know, and hopefully whoever is investing is contributing to those business decisions, but most of the decisions are scientific and the recognition that companies have different stages and need different expertise is less common than it should be.
• 22:18
  Speaker 2: It's perfectly appropriate for scientists to be starting up a company and making those decisions, but when you reach, you know, clinical stage, maybe the leadership needs to be different, maybe you're at a different, you need different expertise, and I see companies make this pivot all the time and I see others who can't make the pivot and make a lot of mistakes as a result.
• 22:44
  Speaker 2: So the first part of it is just recognizing that different phases need different, not to say leadership, but different expertise and different team.
• 22:54
  Speaker 2: A different expertise, a different team.
• 23:04
  Speaker 2: The other important piece is that people who have had a success in bringing a drug to market, a lot of them think that they now have brought a drug to market and therefore they can bring drugs to market.
• 23:15
  Speaker 2: If you have brought one drug to market, you brought one drug to market.
• 23:20
  Speaker 2: Yes, every drug, every asset is different.
• 23:24
  Speaker 2: Every patient group is different, every indication is different, every drug development process is different, and one of the hazards that we see is people and companies who've had one success think that that success translates to the next asset, that they can just do the same things again.
• 23:44
  Speaker 2: Certainly, there's value in having that successful experience, but you have to be open to the fact that the tactics you used the last time may not be appropriate to accomplish the strategy you've got for this, this instance, yeah, and so having that real realization is really important to, uh, to a successful drug development program that that makes sense.
• 24:12
  Speaker 1: Um, what about the drugs that never make it to the market?
• 24:20
  Speaker 2: Sadly there are a lot of those and the ones that don't make it because the science doesn't work, it's not safe, it's not effective.
• 24:30
  Speaker 2: Fine, I mean.
• 24:32
  Speaker 2: Certainly there's lessons to learn from every failure.
• 24:34
  Speaker 2: The question is, what's the damage that is done to that company by that failure, you know is, does the company no longer exist?
• 24:44
  Speaker 2: Is there a failure because of a fixable flaw or a non fixable flaw?
• 24:49
  Speaker 2: You know, those kind of things happen all the time and sadly though, certainly in rare disease, we see more than half of the failures happen because they can't get enough patients in the trial or they can't keep patients in the trial, and so these are fixable flaws, but they're flaws that keep us from learning whether the drug works or not.
• 25:14
  Speaker 2: So we don't get to learn the lesson.
• 25:18
  Speaker 2: The important lesson is does the science work or not?
• 25:20
  Speaker 2: Because that's what leads to more science and we don't get to learn the lesson because the trials are often designed in a very inefficient way.
• 25:27
  Speaker 2: Too many patients needed in the trial Rare diseases although there's many rare diseases, they're called rare because they're rare and patients are spread far apart, and it's difficult to do a rare disease trial, and so you need to have a reasonable number of patients in each phase, and there are designs that can be used to minimize the number of patients.
• 25:55
  Speaker 2: You need to achieve the goal of that phase.
• 25:57
  Speaker 2: In addition, you you know you've got already medically burdened patients who you're putting the burden of a clinical trial onto, and so you have to unburden that trial as much as possible.
• 26:11
  Speaker 2: So what can be done in the patient's home, on the patient's time, what you know, what procedures can be avoided because they're not actually adding to the ultimate goal of that trial?
• 26:25
  Speaker 2: You know, as a former scientist, I guess I'm still a scientist, but you know, I know in academics we pile and we collect every data point we can right.
• 26:35
  Speaker 2: That's what a scientist does.
• 26:37
  Speaker 2: But in a clinical trial, a lot of those data points are really irrelevant to the goal of the trial, and so everything becomes a trade-off.
• 26:45
  Speaker 2: Do you add burden to the patient to get this data point if it's not going to contribute to approval, et cetera, or contribute to your safety assessment?
• 26:56
  Speaker 2: Contribute to approval, et cetera, or contribute to your safety assessment?
• 26:59
  Speaker 2: So I think we have to look at each of those trials and the measures that we're conducting to make sure that we're not making this so burdensome that patients drop out?
• 27:09
  Speaker 1: That makes sense.
• 27:10
  Speaker 1: Is there a way to reinvigorate a drug where we don't really know whether it works or not, or that we know it works but unfortunately the company was not able to bring it to market?
• 27:29
  Speaker 2: So there are folks who are doing that.
• 27:32
  Speaker 2: It's an untapped gold mine because it's likely that some of those are very effective drugs that would have made it through us At least some of them would have.
• 27:44
  Speaker 2: So if you were, if you've got, you know, a pot of money and you've got enough money to buy these, you know they're distressed assets right that you can.
• 27:54
  Speaker 2: You can buy them for pennies on the dollar.
• 27:56
  Speaker 2: Distressed assets right that you can.
• 27:57
  Speaker 2: You can buy them for pennies on the dollar and buy a bunch of them.
• 28:00
  Speaker 2: And if one or two say, you buy 10 and and you should expect that just based on the odds that one or two are going to hit, so from a business perspective, from a financial perspective, that's a pretty good investment.
• 28:12
  Speaker 2: If more than two hit, it's a really good investment.
• 28:18
  Speaker 2: Three or four hit.
• 28:20
  Speaker 2: And the thing is, a lot of these drugs have been de-risked to some degree.
• 28:24
  Speaker 2: Maybe they failed at phase two, so they've already gotten FDA approval to advance to phase two.
• 28:31
  Speaker 2: Meaning there's already phase one data, there's preclinical data.
• 28:36
  Speaker 2: What needs to be?
• 28:37
  Speaker 2: What needs to happen?
• 28:38
  Speaker 2: What needs to be redesigned?
• 28:40
  Speaker 2: Is it just a study?
• 28:41
  Speaker 2: Redesign and do a more efficient program and all of a sudden you can get your answer.
• 28:48
  Speaker 2: Do that for 10 assets that are sitting on the shelf somewhere.
• 28:52
  Speaker 2: To me, it's a.
• 28:54
  Speaker 2: It's a good play, and there's there's people who are doing this, who are doing exactly this buying up groups of assets and seeing what they've got Things like gene therapies that normally would have been really expensive.
• 29:07
  Speaker 2: Tons of those are sitting on the shelf.
• 29:11
  Speaker 1: Yeah, that is an area that has been struggling with investment also.
• 29:14
  Speaker 2: Yeah, well, I mean, gene therapy is a little bit of a different animal in that you know these vehicles that we've been using, av, et cetera.
• 29:23
  Speaker 2: You know the vehicle is really the challenging part.
• 29:28
  Speaker 2: You know, in terms of targeting, et cetera, I think vehicles are going to improve.
• 29:33
  Speaker 2: You know why they all died off is because the investment that has been made in getting those to the point they were at was so high that the expected return you know what was going to be paid for.
• 29:46
  Speaker 2: On the cost, perhaps the economics makes sense.
• 29:49
  Speaker 2: Yeah, yeah, you know, and even if they don't work forever, if they work for two to three years or four to five years, whatever it is, till the next generation of gene therapies come along, that's not a bad thing.
• 30:18
  Speaker 1: Absolutely, and this is kind of the investment in base research that we all benefit from, but that is like disproportionately costly until we find, like that model that works to generate more and more vehicles.
• 30:34
  Speaker 2: Yeah.
• 30:34
  Speaker 2: So just to kind of clarify a bit.
• 30:37
  Speaker 2: So the initial research is costly, but I would say its biggest cost is risk, right, because the highest chance of failure is there.
• 30:48
  Speaker 2: Certainly, one could argue clinical trials are more costly.
• 30:53
  Speaker 2: However, when things reach clinical trials, there is some degree of risk abatement because the preclinical work is done.
• 31:00
  Speaker 2: So really, when we talk about things failing, it's not a matter of that.
• 31:07
  Speaker 2: It costs a lot to do these things.
• 31:10
  Speaker 2: It's when do they fail?
• 31:11
  Speaker 2: We want things to fail.
• 31:13
  Speaker 2: If they're going to fail, I want it to fail early as possible.
• 31:17
  Speaker 1: Yeah.
• 31:18
  Speaker 2: Right Before we've invested all this money so we can learn from that failure, and I think I forget the book.
• 31:24
  Speaker 2: Somebody talked about successful failure.
• 31:25
  Speaker 2: That's a critical point here is we don't want things to fail at phase three.
• 31:32
  Speaker 2: We want things to fail at preclinical or phase one, you know, before we've invested a ton of money and exposed a bunch of patients.
• 31:41
  Speaker 2: We want to understand why it failed.
• 31:43
  Speaker 2: And if you're a single asset company, hopefully you got enough runway to relaunch, correct some things and relaunch, and that's what we need to see more of.
• 31:53
  Speaker 2: So it's not just about how much is being spent, it's when it's being spent.
• 31:58
  Speaker 2: And can we get to the failure point when we talk about academic, you know, grant based science, sadly, you know.
• 32:07
  Speaker 2: I mean it's great that as a scientist, I loved that my grants were five years long, but human nature is, I'm going to do five years of work, Right.
• 32:16
  Speaker 2: But what if?
• 32:17
  Speaker 2: What if, if, if we were doing things in a slightly different way?
• 32:21
  Speaker 2: What if we could know in nine months that we need to change directions?
• 32:25
  Speaker 2: Yeah, yeah we can speed up the process de-risk because we're having successful failures.
• 32:32
  Speaker 1: Yeah, and failures lead to more knowledge and more successes in the long term.
• 32:40
  Speaker 2: Absolutely, and we have to fail to learn.
• 32:42
  Speaker 2: Yeah, and frankly, if you look at the FDA approval rates, most drugs fail.
• 32:49
  Speaker 1: Yes, this is true.
• 32:52
  Speaker 2: So if you're going to fail, fail early yeah.
• 32:54
  Speaker 1: Yeah, also from an investment standpoint.
• 32:57
  Speaker 1: Then we can invest more money in the more promising drug candidates and less in the ones that are going to fail anyway, absolutely, and we don't waste time.
• 33:08
  Speaker 2: Time is money in this case too, and it is the lives, yeah.
• 33:14
  Speaker 1: We touched upon this a little bit in the beginning, but there is a difference between rare diseases and now I forget the word the rare disease, common disease, common disease.
• 33:26
  Speaker 1: The rare disease, common disease, common disease.
• 33:31
  Speaker 1: Um, what makes the rare disease space unique and and why is there more pressure in this space?
• 33:35
  Speaker 2: yeah.
• 33:36
  Speaker 2: So if you are, let's choose a common disease, say hypertension, okay, so for so high blood pressure, you there's lots of drugs on the market but somebody's got a new one and it goes through clinical trials and, importantly, you know they're.
• 33:56
  Speaker 2: They can study thousands of patients, because there's lots of patients with with hypertension and they can get the answers.
• 34:06
  Speaker 2: They're looking for attention and they can get the answers they're looking for and ultimately, at the end of the day, whatever they spent say it's a billion dollars on the whole process of discovery and clinical trials and all of that it's going to be spread over.
• 34:18
  Speaker 2: That cost Recovery is going to be spread over millions of patients, right and so from it.
• 34:25
  Speaker 2: From the standpoint of inefficiencies and other things that are built into that process, they don't matter very much because at the end of the day it's a distributed risk.
• 34:33
  Speaker 2: You know it's a couple of pennies more on a patient or a payer really Now take rare disease.
• 34:43
  Speaker 2: So now you have a limited number of patients say you know 150 patients in the US for a particular disease and you've got an asset that you're developing.
• 34:53
  Speaker 2: And because at the back end, if you're going to spend a billion dollars developing that asset, that that cost recovery is that that burden is on that smaller group of patients and which means that each patient is bearing more of the burden of the cost or the payers for those patients are and by virtue of that, the amount of the total cost of the drug, more of it, a larger percentage of it, is inefficiencies.
• 35:27
  Speaker 2: Also, because it takes almost as long to develop those drugs.
• 35:31
  Speaker 2: It takes longer in many cases.
• 35:34
  Speaker 2: The patent time is short, so the exclusivity time is short and that means that that small group is bearing that burden and that cost recovery over a shorter period of time, and that's why you end up with these $3.5 million a dose drugs.
• 35:52
  Speaker 2: So it's much more important to get the inefficiencies out of those trials so that the cost burden isn't as much when it reaches the end.
• 36:02
  Speaker 2: And you can do that.
• 36:05
  Speaker 2: But again, some of that is just efficient conduct of the trial, early failure, successful failure or just quick movements, not wasting time with various legacy type of activities that don't contribute value.
• 36:23
  Speaker 2: Value.
• 36:29
  Speaker 2: And then at the end of the day, if you're completing faster, you've expanded that exclusivity period and so now it's say two years or three years instead of one year, and at that point then that cost burden, which hopefully is less, is now spread out over the same number of patients but over a longer period of time.
• 36:46
  Speaker 2: And I've had multiple pharma CEOs tell me that time is their biggest.
• 36:52
  Speaker 2: That's the most valuable thing to them.
• 36:55
  Speaker 1: Yeah, that makes sense.
• 36:58
  Speaker 1: So it's different factors, but just like the pure amount of patients and drug makes a big difference and leaves us less room for unnecessary spend.
• 37:14
  Speaker 2: Yeah, it's simple economics, and you just don't have the luxury of having inefficiencies when you have only 100 patients or so that can take the drug.
• 37:23
  Speaker 2: When you have millions of patients, the inefficiencies don't matter as much.
• 37:27
  Speaker 2: Sure, it may be great to be able to get rid of the inefficiencies don't matter as much.
• 37:28
  Speaker 2: Sure, it may be great to be able to get rid of them, but it doesn't matter as much on a per patient basis.
• 37:35
  Speaker 1: Well, Rob, you are one of those people who seems to understand the entire drug development lifecycle and how to commercialize a drug.
• 37:44
  Speaker 1: How did you acquire this knowledge?
• 37:47
  Speaker 2: cycle and how to commercialize a drug.
• 37:50
  Speaker 2: How did you acquire this knowledge?
• 37:51
  Speaker 2: I would say by making all the mistakes that I talk about.
• 37:59
  Speaker 2: Making, you know, trial and error, spending all those years in academia.
• 38:03
  Speaker 2: You know, as a physician and a scientist, getting grants, writing papers, seeing the inefficiencies of our medical system, seeing patients who need drugs not be able to get them and, frankly, see the processes that companies go through at academic medical centers to try to get a trial for one patient or zero patients.
• 38:26
  Speaker 2: There's just a ton of inefficiencies and, as a former emergency physician and chief of emergency medicine, I don't have a lot of patience for inefficiencies.
• 38:37
  Speaker 2: Things have to move quickly and purposefully and so I've seen those mistakes made.
• 38:43
  Speaker 2: I've made a lot of those mistakes and I want to try to help people avoid them.
• 38:48
  Speaker 2: And, and frankly you know, there's a patient at the end of everything we do.
• 38:53
  Speaker 2: Everybody in the drug development space there's.
• 38:57
  Speaker 2: There's a patient at the end of it and in many cases, in rare disease, that patient's life depends on us doing our job the best we can.
• 39:05
  Speaker 2: And are we going to get all the inefficiencies out?
• 39:08
  Speaker 2: Of course not.
• 39:09
  Speaker 2: But can we do it faster and safer and get more of these drugs to market, absolutely.
• 39:16
  Speaker 2: There's just too many drugs, as you mentioned, sitting on shelves that, frankly, could be saving people's lives.
• 39:24
  Speaker 1: Yeah, it's a travesty when it comes to.
• 39:28
  Speaker 1: One of the things that I would like to change in our industry is this huge barrier to entry.
• 39:36
  Speaker 1: It takes a very long time to understand what our life science is about and how do we navigate, and one thing is like becoming proficient in the individual business functions that we have.
• 39:49
  Speaker 1: Another is gaining this experience of well, how do they all fit together and how can we actually optimize In your thinking, how could we reduce that lead time before a person entering life sciences is proficient enough to actually be able to bend the processes and the ways things are to be more efficient?
• 40:12
  Speaker 2: Yeah, so I think this comes back to that transition.
• 40:16
  Speaker 2: So academia creates a lot of this science right and that's critically important and we want more of that.
• 40:25
  Speaker 2: We want more science and we want more of it to come out, because academic medical centers are great at developing the science but not so great at getting it to market Right.
• 40:38
  Speaker 2: That's where that academic industry partnership needs to happen.
• 40:48
  Speaker 2: Transfer process, as you know, talking to a lot of tech transfer professionals, you know they're very frustrated with the inefficiencies of the process, the difficulty getting things out, the difficulty, matchmaking.
• 40:54
  Speaker 2: I mean that's what it is.
• 40:55
  Speaker 2: You know, tech transfer is matchmaking.
• 40:57
  Speaker 2: Who wants this technology, who can make it work?
• 41:01
  Speaker 2: And, frankly, we don't have good systems for that.
• 41:04
  Speaker 2: I mean, some places do better than others, you know, and have created ecosystems by which, you know, investigators can spin it out themselves or and there's support structures to teach them the ropes.
• 41:16
  Speaker 2: Because, let me tell you, academia is not business.
• 41:20
  Speaker 2: It's a different business, but it's not life science business and the skills don't necessarily transfer, and so there's a lot of support structure that needs to be in place to help scientists make that transition.
• 41:36
  Speaker 2: I mean, frankly, they know their science better than anybody and I wish our system.
• 41:40
  Speaker 2: I don't have the answer, but I wish our system was better at that matchmaking process to get them out, at that matchmaking process to get them out, give them the tools that they need to make that transition successfully.
• 41:53
  Speaker 2: And again, I don't know the answer.
• 41:57
  Speaker 2: I've seen lots of different models and some have had more success than others, but there's a lot of great science that just sits in academia and never makes it to the right places and I wish there was a solution.
• 42:13
  Speaker 2: I don't know what it is.
• 42:13
  Speaker 2: I would love to hear people suggest things.
• 42:17
  Speaker 1: Yeah, me too.
• 42:18
  Speaker 1: That would be a great nut to crack.
• 42:20
  Speaker 1: Well, Rob, I've shared one of my wishes for a change in the life sciences industry.
• 42:27
  Speaker 1: Now it's your turn.
• 42:28
  Speaker 1: If I was to give you the transformation and trials magic wand that can change one thing in the life sciences industry, what would you wish to change?
• 42:36
  Speaker 2: I would.
• 42:37
  Speaker 2: So you're going to laugh because it's a super simple thing, but I think a would solve a lot of our issues is people are still afraid to talk to regulators, afraid to share all the details because they've got company secrets.
• 43:07
  Speaker 2: Regulators afraid to share all the details because they've got company secrets.
• 43:10
  Speaker 2: You know, a lot of times poor communication is at the root of inefficiencies and, frankly, failures, and I just wish people were more open.
• 43:25
  Speaker 1: This is actually not the first time that a guest wishes for that.
• 43:29
  Speaker 1: Really, there's a.
• 43:31
  Speaker 1: I thought it was crazy.
• 43:32
  Speaker 1: It's.
• 43:34
  Speaker 1: It's actually the third most wished for.
• 43:37
  Speaker 1: Uh, change in our industry, like openness, openness for collaboration, openness about the challenges that we have, a to discuss how the dynamics of the drugs work and also where else could we apply this specific drug.
• 43:52
  Speaker 1: So I think you're onto something that would be a real game changer.
• 43:57
  Speaker 2: I agree and I get excited when people do have an open conversation with us and just share everything that they're seeing, and because I think that's how we solve things right.
• 44:12
  Speaker 1: Absolutely.
• 44:13
  Speaker 2: Critical.
• 44:14
  Speaker 1: Well, Rob, if someone does want to have an open conversation with you, where can they reach you?
• 44:21
  Speaker 2: So the company is Uncommon Cures and they can go to our website uncommoncurescom and submit to the contact thing there and it'll find me, or they can find me on LinkedIn.
• 44:34
  Speaker 1: Yeah, Also a good place.
• 44:36
  Speaker 1: Well, Rob, thank you so much for joining me today.
• 44:39
  Speaker 1: This was excellent.
• 44:40
  Speaker 1: My pleasure, Ivana.
• 44:40
  Speaker 1: This was so much fun.
• 44:41
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• 44:46
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• 44:50
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