Latest / The BioHub - by Avetix / Episode 133 - Ronald Li & James Kim - CEO and Chief Corporate at Medera respectively ficer at M

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Episode 133 - Ronald Li & James Kim - CEO and Chief Corporate at Medera respectively ficer at M · The BioHub - by Avetix

0:06
So welcome back to the episode of the Bio Hub.
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Today we're delighted to welcome on Ronald Lee and James Kim, who
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served as CEO and Chief Corporate Affairs Officer at
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Madera Biopharmaceuticals respectively.
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Madera is a clinical stage company dedicated to next
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generation cell and gene therapies for difficult to treat
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and incurable diseases. Madera's clinical and
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preclinical programs target a range of cardiac, vascular and
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muscular indications, including heart failure, Duchenne muscular
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dystrophy and pulmonary hypertension.
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And so join us today as we'll discuss Madera's cardiac gene
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therapy pipeline, the next major milestones for Madera and
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Madera's most recent Ind approval.
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So guys, thanks so much for coming on.
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How are you? Very good.
0:49
Thank you, Tom. Good.
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Good well, look, it's a it's an absolute pleasure to to have you
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both on today. So let's just start off with a
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bit about both of your journeys. So James, let's start off with
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you. What what drew you to the team,
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Madera the company and then Ronald will go with you after.
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What inspired you to to found Madera as well?
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Sure. So in terms of me, my background
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was more finance oriented. So I was a warden undergrad,
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started out my career as an investment anchor thinking that
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I was going to just transition to private equity or enter the
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hedge fund world. And maybe it was the
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subconscious guilt toward my parents for not being a doctor,
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but I gravitated more towards the biotech and pharma sector
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and spent about 20 years in Bany as a managing director covering
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biotech companies at Jeffrey's, Cantor Fitzgerald and Stifel.
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And about two years ago made the transition over to the corporate
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side as CFO of a private cell therapy company in in March
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slash April of last year as Chief corporate officer at
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Madera. And the rationale for the
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transition it was that I became more interested in immersing
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myself into the science, learning more about operating a
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biotech company reached a point in my life where I started being
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motivated in my career by other factors.
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So I I made the move. As it.
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Pertains to joining Madera, I was a big believer in selling
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gene therapy, going through its peaks and valleys to become just
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as impactful on small molecule and antibody.
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And it was good that Ron and Rogers working to feel lent a
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lot of credibility to the company.
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And as I dug into the science, it was clear there was a a
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differentiation with the Madera versus other gene therapy
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companies, the intraporinar delivery that allows for 100
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times less dosing versus IE gene therapy outpatient procedure
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with no immunosuppression regimen.
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Functional human data validating our approach where I I thought
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my expertise, background, capabilities could help put it
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all together to convey a compelling story to the market
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and help the company execute transactions to progress the
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pipeline and generate value. Yeah, Ronald.
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And what, Yeah. What, what inspired you to to
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found Madera? What I guess what were you
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looking to address at the time? Sure.
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So for me founding Madera with my Co founders Roger Jar and
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Kevin Costing was really like a natural next step for us.
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The three of us came come from the same backgrounds in
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biomedical engineering and cardiology.
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And for the past 25 to 30 years, our work really has been
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focusing on developing cell and gene therapies for difficult to
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treat and incurable cardiovascular diseases.
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And historically, we used to license our technologies out
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after proof of concept and relied on others to take them
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forward over time. And at some point, we felt that
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there was a real need to step outside academia and take
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greater ownership, combining scientific rigor with real world
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execution. So Madera was built to be
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grounded in human biology first, translating cardiac insights
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into tangible technologies and therapies to eventually benefit
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patients. So that was the original
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motivation. Amazing.
4:36
And just to delve in into a little bit into the platform.
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So it's a unique discovery platform, which I know is his
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name, the human mini heart. You just give us a brief
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overview of and explain how it works and why.
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Why you think it's a game changer in in cardiology
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research? Absolutely.
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I mean, you know, I'll keep the Long story short, but basically
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a heart failure, I mean, as we all know is a global epidemic.
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But many people, what many people don't realize is that the
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heart, it's also the single biggest hurdle in drug
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development across basically all therapeutic areas.
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It doesn't matter what drugs you are developing, you know, for
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cardiac, for cancer, for developing A painkiller, for
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arthritis, you know, whatever. I mean whenever you develop a
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new drug, roughly half of the drug failures have to do of
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cardiac safety. So lastly, because the industry
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really has been depending on animal models, which we now know
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they do not reliably predict human heart responses.
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And with the FDA's modernization at 2.0, there is a clear shift
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to what human based technologies and they called it new
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alternative methodology and Nam. So Almenia human meaning heart
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platform is exactly that. So we can engineer, we can
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basically fabricate healthy human heart chambers to assess
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toxicity. At the same time, we can also
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construct sick diseased mini human hearts to evaluate
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efficacy entirely in in the context of human hearts.
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So this really allows us to discover, validate and even
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titrate dosages before they ever reach patients and thereby
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reducing the time it takes the cost, reducing the cost and most
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importantly improving the success rate.
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That's why we were so excited to receive from the FDAIND
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clearance fast track destination and therefore now we are running
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two active car failure gene therapy clinical trials and also
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with their phase one sets to a trials completed as well.
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Amazing. Just to delve a little bit into
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the, the pipeline a little bit more.
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So can you give it an overview of, of Madera's cardiac gene
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therapy pipeline and yeah, what, what makes the approach
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different from other therapies that are in development at the
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moment? That would be, yeah, amazing.
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Yeah. We.
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Are taking a common disease approach.
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So we have two trials, one for two trials for heart failure,
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one for heart failure with reduced ejection freshen, the
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other one is for half failure with preserved ejection freshen
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and together they cover the entire half failure patient
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population of around 64,000,000 patients worldwide.
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So our pipeline, we also have a rare disease approach and that
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is for the chain muscular dystrophy related
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cardiomyopathy. And our pipeline targets the
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core biology of heart failure and cardiomyopathy, particularly
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what we call calcium handling for cardio myocardial function.
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So rather than focusing on rare genetic mutations one at a time,
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so genetic 1 genetic mutation for one genetic disease instead
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of approaching them one at a time.
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Our approach is an umbrella pathway disease approach,
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meaning that the protein we target that we have identified
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and also has been independently validated by many others as
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well. So the protein that we target is
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universally down regulated across most if not all forms of
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heart failure and cardiomyopathy.
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So whether genetic or acquired, so by restoring this missing
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protein, our therapies, our trials have the potential to
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treat multiple cardiac diseases with a single mechanistic
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approach. So we want to, we want to be
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able to, you know, describe it as a universal approach.
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That's why we are running trials in two major forms of heart
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failure as I described before, covering a patient population of
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over 64,000,000 globally and also extending into genetic
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conditions such as the Shea muscular dystrophy associated
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cardiomyopathy, which is a rare disease and a rare disease
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approach. So importantly, I mean as I
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briefly described before about the mini Heart technology
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platform as well. So every program at designed and
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validated using the Human Mini Heart technology platform before
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entering the clinic actually as part of the packages that we
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submitted to the FDA for the initial Ind clearances as well.
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So that by giving us much more higher confidence in both
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efficacy and safety. Amazing.
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Yeah. Just just I guess just an
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additional question on that. So I never like to use the word
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competitors because I always think what what biotechs are
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doing, it's all it's all for the patients.
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But if you look at like who are the companies that are doing
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similar work to you guys like who are the the companies in
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that space that again, I don't like to use the word compete in,
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but I guess you're sort of up against.
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I would say what really differentiates Madeira from
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other comparable players in the field is that we are using the
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so-called intra coronary delivery method which allows us
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to directly inject our gene therapy drug into the heart.
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And by doing so there are multiple benefits.
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We don't have to apply any immunotherapies, no steroid or
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whatsoever. And clinically we haven't seen
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so far to date a single severe adverse events of safety is is
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extremely, extremely important through the lens of the FDA and
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we haven't seen any other side effects, absolutely no T cell
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responses, no liver damage or whatsoever.
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So and by injecting into directly injecting into the
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heart, I mean as James mentioned earlier, we are able to reduce
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the dosage by more than 100 times compared to conventional
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systemic IV infusion. So by I mean as you can imagine
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when we are injecting 100 foot less viral particles as the
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vehicles, you know this is our gene therapy drug.
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We are also proportionally reducing the cost of goods as
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well. So we believe that when the time
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comes for us to to make the drug available for patients, we can
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also be able to price very competitively to, to, you know,
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to to to make this, you know, I mean, as you know, people
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usually complain that gene therapy trucks are extremely,
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prohibitively expensive. We think that we are looking at
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like a huge patient population because this is heart failure, a
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common disease 64,000,000 patients worldwide.
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And we feel that practically in the real world, to be able to
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make the drug relatively more affordable by reducing the cost
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is also extremely important. Amazing.
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You guys obviously went through a recent Ind approval as well
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recently. So massive, massive
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congratulations on that. Can you just talk us through the
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the process of of obtaining that Ind approval and might such a a
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significant milestone for for Madera?
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Well, I think Ind approval is a critical first step, you know in
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any clinical development program, most biotech companies
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I would say. So it requires alignment across
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preclinical biology, manufacturing, toxicology and
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importantly of course the clinical trial design for Madera
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I think it was a major validation point because
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regulators agree that our human based data package collected
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using the Mini Heart human mini Heart technology platform was
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robust enough to support first in human studies.
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So it marks our transition from platform innovation, you know
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into true clinical execution. And we are very excited that in
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2025, we have completed the enrollment for not only one, but
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two phase one Phase 1/2 A trials and the data are coming in and
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we have so far very happy with the outcomes.
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Just to add, it's exciting to see SRD 002 for half half for
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example, which is first gene therapy for half path a
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prevalent indication with significant unmet need.
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As Ron mentioned, it's a very a prevalent condition affected
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noise of patients, but there really hasn't been any new
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treatment. Standard care already manages
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certain parts of the disease given it's so heterogeneous in
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terms of characteristics, a lot of comorbidities and a, and
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we're excited and we're seeing some exciting data there a,
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where a, it's one and done. We're actually reversing the
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Physiology that defines half path and treating the underlying
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cause of half half symptoms. I mean, that's something we
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haven't seen before with standard care or other novel
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treatments that are currently in development.
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So we're, we're, we're very excited we're able to clear eye
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and the conduct phase 12IN starting to churn out very good
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data there. Yeah.
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As a supplement, we presented the food cohort aid data, the
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low dose cohort. We presented the data recently
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at the American Heart Association as one of the late
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breaking clinical trials. So as I said, we have completed
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enrollment for the second cohort which is that high dose as well.
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So, and, and now we're just collecting the time course data
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and so far things have been very encouraging and we can't wait to
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announce and make out, you know, data readout announcement in the
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in the foreseeable future. Amazing.
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And just whilst we're on sort of milestones like what, what's
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next few guys that and he mentioned a couple of things
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then, but if you look at the next milestones in terms of
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funding, commercialization, clinical trials, like what are
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the next milestones are you both looking forward to?
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Or you got to be a near term clinical readout.
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So we are, I mean, you know, we believe that that gene therapy
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obviously is, is interesting and the field is really becoming
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mature and growing. We are happy that investors,
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scientists, clinicians are now asking more questions, asking
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more questions about safety not only and, and that efficacy, you
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know, pricing and things like that.
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I mean, you know, for, for me, it indicates that the food's
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becoming mature, but it, it's absolutely for us, it's going to
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be, you know, the clinical readouts.
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So we've seen preliminary data and as I said, we're presented
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the, the entire cohort food data set at the American Health
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Association and we're going to be making more announcements.
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So it absolutely and the near term clinical readouts are going
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to be important. The pipeline expansion, it's
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also something that we've been working very hard on as well.
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So we are in the process of, we've been in the process of
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forming strategic partnerships, commercialization planning and
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and all these have been designed to compound really both clinical
16:08
impact and long term enterprise value and.
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What about like on a funding side of things?
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Is that you guys hoping to close another round this year?
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Like where? Where are you at on that side of
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things? No, absolutely.
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So we've been working very hard then you know, we talked about
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how the market has been like in the in the in the past year or
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two or longer, right. So and now we really want to be
16:32
able to capture some opportunities and you know,
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complete around and move on. And also there's there are a lot
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of corporate development plans that we have in mind as well.
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So you know, 2026 is going to be an exciting year for us.
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James, question for you, how do you see this sort of cardiac
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gene therapy space evolving over the next five years and and
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where Madera may fit in that landscape, like how do you see
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yeah, but that space evolving from where it is now?
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Sure. I, I think first and foremost to
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we're going to continue to see focus by a lot of these
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companies to lower dose to mitigate immunogenicity, liver
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toxin, other S ES you're hearing they just be able to lower dose.
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A key part of a lot of is strategy for a lot of these
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companies and systemic tube therapies are relying on
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specific serotypes, novel promoters and other
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modifications to try to increase tropos in the heart, increase
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transduction. And they haven't gotten the dose
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down from 10 to the 14th vector genome per kilogram to 10 to the
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13th vector of genome per kilogram.
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But as Ron mentioned before, with our technology, we're able
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to get it down even further, 100 times less where it's 10 out of
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13 vector genome total not per keg.
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And as a result, we have not seen any SA ES on from three
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ongoing Phase 1-2 trials where we've dosed over 21 patients.
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So that's exciting. The other factor, a trend AIC is
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I think we're going to continue to see technologies, your start
18:15
to see technologies in gene therapy that makes the modality
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viable or larger indications earlier settings offer greater
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patient access. Where is seeing gene editing
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programs for indications like hypercholesterolemia, cell
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therapy for indications like diabetes.
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We're seeing improvements in CMC where cell and gene therapy
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could be more commercially viable for these broader
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indications. Hopefully in the near future,
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we'll see technologies that attenuate, neutralize the
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antibodies, for example, to improve safety, allow for
18:53
redosing and increase patient eligibility of say and perhaps
19:00
treatments like ours or more treatments like ours where
19:04
there's no preconditioning or immunosuppression regimen where
19:09
patients can be dosed in community or outpatient
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settings. Obviously, you're a small
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company. How do you guys prioritize like
19:17
not only advancing clinical trials but expanding discovery
19:20
capabilities, trying to scale the company globally at same
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time? How do you manage all that, and
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which partnerships or collaborations do you see is
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most critical to Madera's growth and and success?
19:33
It really hasn't been easy. I mean, we have the, we have
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been conserving the resources to really focus on our top priority
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programs. And so far it really has been
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the heart failure we're preserved ingestion fresh and
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SLDO O2 that James was mentioning.
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It's a first in human gene therapy for, you know, that this
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condition which afflicts surfer 10s of millions of patients
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worldwide without good disease more than fine drugs.
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But at the same time, you know, as biomedical engineers, we've
20:07
we've been developing a wide, a rather wide technology platform
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as well. And we've been spending a
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tremendous amount of time and efforts and energy to to make
20:19
sure that the, the, the platform really works.
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The way we think it does and that that has been done to a
20:28
great extent been validated and now you know, going forward we
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just want to make it available for broader usages by the
20:38
industry and a good way to do as I hinted earlier is that to form
20:43
partnerships with different companies.
20:45
So the and we are in the process of forming a major partnership
20:51
with a global company and I think we'll be ready to make an
20:54
announcement in, in a very soon and we're very excited about
20:59
that as well. Wow, super exciting.
21:01
And look, just just to finish this off, if you guys, I'll
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start with you Ron, but if you were to host any three people
21:10
for dinner past or present, who would you go from?
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Why? And then James will, we'll go
21:14
with you after. I would have to say my mom, my
21:19
mother who passed away a few years ago, it would be really
21:22
nice for, for me to be able to have even just a dinner and with
21:26
her and without prioritizing, right?
21:32
So the I'm, I'm, I, I would like to be seen as a devoted
21:35
Christian. So I would have to say that I
21:37
would like to be able to have dinner with Jesus and ask him
21:41
what my role really is and what he wants me to do.
21:44
And the third one I, I want to, I want to reserve that for, you
21:50
know, for future. For me, it's interesting Rod,
21:54
you and I like because my companions, dinner companions
21:58
are more personal than career oriented.
22:01
So. I have two kids at a home.
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I one in high school, one in middle school, and my wife is
22:07
the disciplinarian in the family.
22:10
And occasionally, or more occasionally or more frequently,
22:13
it's Warzel where I have to play Sweden.
22:17
And. What I would like to do is have
22:19
dinner with my wife in high school and my children in their
22:24
40s and record the dinner conversation.
22:28
So and I think we'll I'll be able to get some good content
22:33
there where the next time they fight I can replay.
22:36
TV. Conversation from the family
22:39
dinner to try to broker peace through or have some peace and
22:42
quiet in the house and hopefully it works.
22:46
Wow. Yeah, well, I love that.
22:48
That's a good way to do it. So yeah, look, thanks so much
22:52
for coming on and helping us out with this, guys.
22:54
I'm super excited to follow the progress of you guys.
22:57
It sounds like you've got a super exciting year ahead of you
23:00
as well. So yeah, it sounds like what
23:03
you're building is amazing. And yeah, thanks for coming on
23:06
and helping us out with this again.
23:08
Thank you, Tom. Thanks for having us.