28 - Selecting a Development Candidate (S2E13)

Welcome back to the Deep Dive. Today we're going
deep into the world of drug development. Oh yeah.
Focusing on how teams choose the best drug candidate
to move forward with. Right. The best of the
best. Exactly. You've given us a ton of research
papers and articles, even some personal notes
to dig into. It's quite the stack. It's a real
treasure trove. We know you love getting into
the nitty gritty. And this process... Oh, I do.
...is all about making those tough choices from
a mountain of data. That's the heart of it, really,
picking the winner from a sea of possibility.
Okay, so let's break this down. Your research
really highlighted metabolic stability. Basically,
how fast a drug breaks down in the liver. I was
surprised to learn that a rapid breakdown isn't
always a bad thing. Oh, yeah. That's a common
misconception. Can you explain that a bit more?
Sure. So sometimes those breakdown products,
what we call metabolites, they're the real stars
of the show. They can be even more effective
than the original drug. Wow. Or have better characteristics
for development. So it's like finding a hidden
treasure within the drug itself. Exactly. It's
like the drug has a secret weapon. That's a great
way to put it. Your notes also had a case study
on psilococci. Right, a popular pain reliever.
Yeah, showing how a specific liver enzyme, CYP2C9,
plays a major role in breaking it down. It's
a key player, for sure. What's the significance
of that? Well, understanding how these individual
enzymes work is critical. It's not just about
breaking down the drug. I see. It's about knowing
how it's broken down and what those metabolites
do, you know? Right. It helps us anticipate potential
drug interactions. OK. Or even tailor treatments
for people with certain genetic variations. So
it's like personalized medicine. but at the enzyme
level. You got it. That's incredible. And what
about these reactive metabolites I keep seeing
in the research? Oh, yes. Those sound a little
ominous. Well, they can be. They're kind of the
unwanted guests at the party, potentially causing
some nasty side effects. Oh, no. Some drugs have
even been pulled from the market because of them.
Really? Yeah. You remember Vioxx? Wow. It was
a blockbuster pain reliever, but it turned out
to have serious cardiovascular side effects all
because of its reactive metabolites. Wow. That
really highlights the importance of safety testing.
Absolutely. You don't want to release a drug
that does more harm than good. No, absolutely
not. But your research also pointed out some
exciting new tools. Oh, yeah. Like... computer
modeling being used to predict that potential
toxicity early on. That's right. Computer modeling
is becoming incredibly powerful. It allows us
to simulate how a drug might behave in the body
before we even start clinical trials. It's like
having a virtual lab. That's amazing. Helping
us weed out those problematic candidates early
on. And your notes also mention using mouse models
to study how drugs interact with these transporters
in the body. Ah, yes. The gatekeepers. What exactly
are transporters, and why are they so important?
Well, think of transporters as gatekeepers. They
control what goes in and out of our cells. They
play a critical role in how a drug is absorbed,
distributed, and ultimately eliminated from the
body. I see. By studying these interactions in
mouse models, we get a better understanding of
a drug's journey through a living system. It
sounds like a really complex puzzle with all
these different pieces interacting. It's a fascinating
puzzle to solve. But it's not just about the
science, is it? Your research also emphasized
the business side of things. Oh, absolutely.
Like market exclusivity and scalability. Right.
A groundbreaking drug isn't much use if it's
not commercially viable. That's true. Market
exclusivity, protected by patents, is crucial.
It gives a company time to recoup that massive
investment in drug development. Makes sense.
And then, scalability. Can we actually manufacture
the drug efficiently? and on a large enough scale
to meet demand. So it's like a delicate balancing
act weighing the scientific potential against
those economic realities. Exactly. You've got
to consider all these factors before choosing
the best candidate. You really do. It's not just
finding a drug that works. It's finding a drug
that works and has a real chance of making a
difference in the world. You hit the nail on
the head. It's that sweet spot between scientific
promise safety, manufacturability and market
viability. OK, so we've got this mountain of
data about potential drug candidates. Right.
What happens next? How do teams actually sift
through it all and make that final decision?
Well, there are several key factors they consider
first and foremost. Efficacy, does the drug actually
work? Okay. How does it compare to existing treatments?
You know, they really dig into that clinical
trial. data, analyzing everything from how well
the drug performs to its potential side effects.
So it's about crunching the numbers, seeing how
the drug measures up against the competition.
Exactly. But it's not just about efficacy, is
it? Right. Safety is paramount. They scrutinize
that data for any red flags, any hints of toxicity
or adverse reactions. They want to be sure the
drug's benefits outweigh any potential risks.
That makes sense. You wouldn't want to release
a drug that causes more harm than good. No, absolutely
not. And then there's manufacturability. Can
we actually produce this drug on a large scale?
Can we do it efficiently and cost effectively?
That's a practical consideration that I think
sometimes gets overlooked. You're absolutely
right. A brilliant drug is no good if we can't
get it into the hands of the people who need
it. Absolutely. So it's like a three -legged
stool, efficacy, safety, and manufacturability.
I like that. All three have to be strong. for
the drug to really stand a chance. That's a great
analogy. And interwoven with all of this are
those business considerations. Right, those economic
realities we talked about earlier. Your notes
mentioned something called net present value.
as a key decision -making tool. Can you explain
what that is and why it's important? Sure, net
present value or NPV. It's a way of calculating
the profitability of a drug candidate over its
entire life cycle. Okay. So it takes into account
all the costs, research, development, manufacturing,
marketing. Wow, that's a lot. And compares those
to the projected revenue. So it's like a financial
crystal ball trying to predict whether the drug
will be a blockbuster or a bust. That's a great
way to put it. A high NPV suggests the drug has
the potential to be profitable. Right. While
a low or negative NPV raises some serious red
flags. I can see how that would be crucial information
for those decision makers. Oh, it is. But it's
not just about the bottom line, is it? No, it's
not. Companies also consider the strategic fit
of a drug candidate. OK. Does it align with their
overall portfolio and their long -term goals?
So they might choose a drug with a slightly lower
NPV if it complements their existing product
line or opens up a new therapeutic area. Exactly.
It's about making strategic decisions that position
the company for future success. It sounds like
a really complex equation with a lot of variables.
It is. There are a lot of moving parts. How do
teams actually go about weighing all these factors
and making that final decision. Well, they often
use what's called a structured decision -making
process. Okay. Typically it involves a cross
-functional team, you know, scientists, clinicians,
business experts. A variety of perspectives.
Exactly. Who carefully evaluate all the data
and then present their recommendations to a senior
leadership team. So it's not just one person
making the call. It's a collaborative effort.
with multiple perspectives brought to the table.
Exactly, and ultimately the decision comes down
to a judgment call. Okay. There's no magic formula,
no algorithm that can definitively tell you which
drug candidate is the best bet. That makes sense.
It's like a high -stakes... Poker game where
you have to weigh the odds and make the best
decision based on the information you have that's
a great analogy and like any poker game There's
always an element of risk. So how do they try
to minimize that risk? One way is through rigorous
data analysis Okay, they scrutinize every piece
of information looking for any patterns or insights
that might help them make a more informed decision
It's about leaving no stone unturned right making
sure they've considered every angle precisely
They also consider the competitive landscape.
Oh what other drugs are in development for this
particular condition, how advanced are they?
So they're trying to anticipate what the market
might look like. in a few years when their drug
is ready to launch. Exactly. They want to make
sure they're not entering a crowded market where
their drug will get lost in the noise. So it's
like a chess game trying to outmaneuver your
opponents. I like that analogy. They also have
to factor in the regulatory landscape. Right.
What are the requirements for approval in different
countries? Right. Those regulatory hurdles we
talked about earlier. Exactly. Navigating those
hurdles can be a complex and time consuming process.
I bet. They have to make sure their drug candidate
has a good chance of clearing those hurdles.
successfully. It sounds like a lot to juggle.
It is and to top it all off they have to be mindful
of the ever -changing nature of the pharmaceutical
industry. Oh of course. New scientific discoveries,
emerging technologies, evolving market dynamics.
Right. It can all impact their decision -making.
So they're constantly adjusting their strategy
trying to stay ahead of the curve. Absolutely.
It's a dynamic and challenging field, but it's
also incredibly rewarding. After all, they're
working to develop treatments that could potentially
save lives and improve human health. That's a
powerful reminder of the ultimate goal, speaking
of the big picture. Your research also highlighted
the increasing role of artificial intelligence
or AI. Oh, yes. In drug discovery, how is AI
being used in this candidate selection process?
Well, AI can analyze these massive data sets
much faster and more efficiently than humans
can. Wow. It can identify patterns and insights
that we might miss. So it's like having a super
-powered research assistant helping us sift through
mountains of data. That's a great way to put
it. AI can help us identify promising drug candidates,
more quickly predict their potential efficacy
and safety, and even estimate their market potential.
That's incredible. It sounds like AI is revolutionizing
the way drugs are developed. It's certainly having
a major impact, but it's important to remember
that AI is a tool, not a replacement for human
expertise. It's about augmenting our abilities,
not replacing us. Exactly. The final decision
about which drug candidate to move forward with
still rests with human beings. We have to weigh
all the factors, consider the ethical implications,
and ultimately make the best decision based on
the available information. It's a reminder that
drug development is a human endeavor driven by
a desire to improve human health. Speaking of
human health. One thing that stood out in your
research was the concept of patient -centric
drug development. Ah, yes. That's a growing trend
in the industry and for good reason. Can you
explain what patient -centric drug development
means and why it's so important? Absolutely.
It means putting the needs and perspectives of
patients at the center of the drug development
process. So it's not just about developing a
drug that works. It's about developing a drug
that works for the people who will be using it.
Exactly. It's about understanding their experiences,
their preferences, their challenges, and incorporating
that knowledge into every stage of the process.
I can see how that would be incredibly valuable.
But how do they actually go about getting that
patient input? They use a variety of methods.
They might conduct surveys, hold focus groups,
or even partner with patient advocacy organizations.
So they're going directly to the source, getting
first -hand insights from the people who will
ultimately benefit from these new treatments.
Precisely. And they're doing it throughout the
development process, not just at the end. That
makes sense. It's about building a drug that's
not only effective and safe, but also meets the
real -world needs of patients. You've got to...
Patient -centric drug development is not just
about doing the right thing ethically. It's also
about developing better drugs. That's a powerful
point. By understanding the needs of patients,
they can develop treatments that are more likely
to be used and adhere to, ultimately leading
to better health outcomes. Exactly. It's a win
-win situation. This deep dive has been incredibly
enlightening. We've gone from the molecular level,
looking how drugs are metabolized, all the way
to the patient experience, considering their
needs and perspectives. And we've explored that
complex interplay of scientific regulatory and
economic factors that shape the drug development
process. It's been a whirlwind tour, but it's
given me a much deeper appreciation for the intricacies
and challenges of this field. I'm glad to hear
that it's a field that's constantly evolving,
but one thing remains constant, the dedication
and ingenuity of the people who work tirelessly
to develop new treatments that can improve human
health. Before we wrap up, I want to circle back
to something you mentioned earlier, the concept
of risk in drug development. OK. It's a high
stakes game and not every drug candidate is going
to be a winner. That's right. In fact, the vast
majority of drug candidates fail somewhere along
the way. Wow. That's a sobering statistic. Why
is the failure rate so high? There are many reasons.
Sometimes the drug simply doesn't work as well
as expected. Other times it turns out to have
unexpected side effects. So it's back to that
balancing act between efficacy and safety. Exactly.
And sometimes the manufacturing process proves
too complex or too expensive. Or the market landscape
shifts, making the drug less commercially viable.
Right. There are a lot of hurdles to overcome
and most drug candidates stumble at some point
along the way. So how do drug developers cope
with this high failure rate? Well, for one thing,
they embrace the concept of failing fast. What
does that mean? It means identifying and eliminating
unpromising candidates as early as possible.
Rather than clinging to a drug that's not working,
they cut their losses and move on to something
with more potential. That makes sense. It's about
maximizing efficiency and minimizing wasted resources.
Exactly. They also learn from their failures.
Oh, sure. They analyze what went wrong, why the
drug candidate failed, and use that knowledge
to improve their processes for future projects.
So it's about turning setbacks into learning
opportunities. Precisely. Failure is an inevitable
part of the process, but it doesn't have to be
a defeat. It can be a stepping stone to future
success. That's a great perspective. This deep
dive has been incredibly insightful. We've explored
the science, the business, the ethics, and even
the psychology of drug development. We've covered
a lot of ground from the lab bench to the patient's
bedside. It's been a fascinating journey, and
I'm sure our listeners have come away with a
new appreciation for the complexity and importance
of this often -hidden world. I hope so. It's
a world that's full of challenges, but also full
of hope, after all. We're working to develop
treatments that can potentially alleviate suffering
and improve the lives of millions of people.
Before we wrap up, before we wrap up, I'm curious
about something. We've talked a lot about how
teams choose the best drug candidate, but what
happens to the ones that don't make the cut?
You know, the ones that don't get chosen. Oh,
that's a great question. It's not always the
end of the road for those candidates. Really?
Yeah, sometimes they're shelved temporarily,
you know. Okay. Maybe to be revisited later if
new research emerges or the market landscape
changes. So they're kind of like seeds in a vault
just waiting for the right conditions to sprout.
Exactly. And sometimes these candidates find
new life in a different indication. What does
that mean? Well, a drug that wasn't effective
for its original purpose might show promise for
treating a different disease altogether. That's
fascinating. So it's like recycling, but for
drug candidates. You could say that it's about
recognizing that even if a drug doesn't hit the
mark initially, it might still hold valuable
potential. That's a great reminder that failure
isn't always final. It can be a redirection,
a chance to explore new possibilities. This deep
dive has been a real eye -opener. I feel like
I've gained a whole new understanding of this
intricate world of drug development. It's a complex
and fascinating process, isn't it? From the initial
spark of an idea to the rigorous testing and
evaluation to that final decision you know about
which candidate to move forward with. Yeah. There's
so much involved. And it's all driven by that
shared goal. of improving human health. It's
inspiring to think about the dedication and passion
of all the people who work in this field. I couldn't
agree more. They're true heroes working tirelessly
behind the scenes to develop treatments that
can alleviate suffering and enhance lives. Well
said. We've covered a lot of ground today, from
the science of drug metabolism to the economics
of market exclusivity to the importance of patient
-centric development. What are some key takeaways
you hope our listeners will remember from this
deep dive? I hope they come away with a deeper
appreciation for the complexity of the drug development
process. It's not a simple or straightforward
path. It's a long and winding road filled with
challenges and setbacks, but also with some incredible
triumphs. It's a reminder that scientific progress
takes time, persistence, and a willingness to
embrace both success and failure. Exactly. I
also hope our listeners will remember the human
element of the story behind every new drug. There
are countless individuals, scientists, clinicians,
researchers, patients, who have contributed their
knowledge, skills, and experiences to make it
a reality. It's a testament to the power of human
ingenuity and collaboration. Absolutely. And
finally, I hope our listeners will be inspired
by the incredible potential of this field. New
technologies like AI and machine learning are
revolutionizing the way drugs are developed,
offering new hope for treating diseases that
were once considered incurable. It's an exciting
time to be following the world of drug development.
Who knows what breakthroughs lie just around
the corner. The possibilities seem endless. Thanks
for joining us on this deep dive. Until next
time, keep learning and keep exploring.