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Pulse Biosciences Brings Differentiated Nanosecond Technology to PFA · Vanguards of Healthcare by Bloomberg Intelligence

• 0:21
  Speaker 1: Welcome to another episode of the Vanguards of Healthcare series.
• 0:24
  Speaker 1: My name is Matt Henrickson, the medical technology analyst at
• 0:27
  Speaker 1: Bloomberg Intelligence, which is the in house equity research platform
• 0:31
  Speaker 1: of Bloomberg LP. We are pleased to have with us
• 0:33
  Speaker 1: today Paul Leviolette, CEO of Pulse Biosciences, a medical device
• 0:38
  Speaker 1: company pioneering nanosecond pulse field ablation. You can dive deeper
• 0:43
  Speaker 1: into the company and as financials by typing in p
• 0:46
  Speaker 1: LSE equity go on your Bloomberg terminal. Paul, thank you
• 0:51
  Speaker 1: for joining us.
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  Speaker 2: Thanks a lot, Matt, good to see you.
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  Speaker 1: Good to see you too, And Paul, I might just
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  Speaker 1: start with what is nanosecond pulse field ablation.
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  Speaker 2: Well, it's really a new energy form that's turning into clinical,
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  Speaker 2: meaningful therapeutic potential as we speak. So let's break it down.
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  Speaker 2: Nanosecond is a phrase that characterizes how short a pulse
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  Speaker 2: of electricity exists. So what's the pulse duration and nano
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  Speaker 2: relates to billions of a second, and so what we
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  Speaker 2: have here is the ability to deliver electrical pulses as
• 1:34
  Speaker 2: a therapy into the body. And they're defined by their
• 1:39
  Speaker 2: ultra short duration. Which allows them to go in and
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  Speaker 2: into the cells and affect cellular processing and create an
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  Speaker 2: ablation in the body, but do so without leaving any
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  Speaker 2: heat trace behind, so it's a non thermal ablation energy.
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  Speaker 2: Nanosecond is a very unique form of a pulsed electric field,
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  Speaker 2: so to be able to combine an ultra short pulse
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  Speaker 2: duration with a very high amplitude of voltage, that combination
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  Speaker 2: of parameters gives us a very unique therapeutic tool, and
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  Speaker 2: we're beginning to explore its use in multiple clinical applications
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  Speaker 2: that are extremely exciting. And if you think most importantly
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  Speaker 2: about how often in clinical medicine around the world is
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  Speaker 2: a Blatian energy delivered today, it's millions of time a
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  Speaker 2: day to treat all forms of unwanted tissue and eradicate
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  Speaker 2: that tissue essentially by burning it. And in the process
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  Speaker 2: of burning it, you leave behind scar tissue, you create
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  Speaker 2: a fibrotic response. It's really rejected by the body, but
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  Speaker 2: it's the only means we have today to treat unwanted
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  Speaker 2: tissues without cert and so along comes nanosecond PFA with
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  Speaker 2: the potential to replace many of those thermal ablation procedures
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  Speaker 2: with a non thermal, very unique alternative.
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  Speaker 1: Interesting, And you know, before we jump into that potential,
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  Speaker 1: let's talk a little bit about your path and how
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  Speaker 1: that path led you to Pulse Biosciences. With your career
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  Speaker 1: trajectory throughout the years, what kind of experiences have you
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  Speaker 1: picked up at your prior companies that have helped out
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  Speaker 1: with Pulse Biosciences, particularly because some of your previous experiences
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  Speaker 1: have been with large cap companies, Pulse Biosciences as a
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  Speaker 1: small cap company, how does that experience help out with
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  Speaker 1: a small cap company?
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  Speaker 2: I think it helps a lot. I've had the privilege
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  Speaker 2: over now a forty five year career in medtech of
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  Speaker 2: as you described, working for large cap companies, leading large
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  Speaker 2: cap companies, and across that span of large cap experience,
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  Speaker 2: I would say it brings me a lot of exposure
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  Speaker 2: to new technology, innovation, new therapy development, and really the
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  Speaker 2: ultimate application of resources to drive innovation. And I also
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  Speaker 2: spent nearly twenty years as a venture capitalist, a venture
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  Speaker 2: investor in medtech, which of course gave me further insights
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  Speaker 2: into early stage innovation. And there's a wonderful, i'd say,
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  Speaker 2: dynamic between early stage innovation and the medtech strategics, and
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  Speaker 2: we of course see the medtech strategics as relatively active
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  Speaker 2: acquirers of early stage technology. Pulse Biosciences is an early
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  Speaker 2: stage company with one indication now FDA approved multiple indications
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  Speaker 2: in the pre commercial stage in clinical development in IDEs,
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  Speaker 2: and I would say my experience historically has given me
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  Speaker 2: number one, the opportunity to manage programs like that, to
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  Speaker 2: see how that can be done in a world class way,
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  Speaker 2: to understand the value of world class talent, and ultimately
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  Speaker 2: how to create both compelling clinical evidence and compelling value
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  Speaker 2: for the enterprise. And so I think pulses very clearly
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  Speaker 2: on its trajectory to both develop compelling evidence and compelling
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  Speaker 2: value as a byproduct of the unique delivery of nanosecond
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  Speaker 2: pulse field deplation.
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  Speaker 1: Now that's interesting because there's a lot of things that
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  Speaker 1: you just mentioned that I've heard many times before, and
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  Speaker 1: one of the things is having essentially a checklist of
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  Speaker 1: getting a product from the drawing board to being commercially available,
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  Speaker 1: you know, building out the clinical data. You know, we
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  Speaker 1: will talk more into kind of the manufacturing ramp and
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  Speaker 1: capacity to get the enough product out there. So when
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  Speaker 1: you do have upda aprool will you get launched? But
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  Speaker 1: I'm curious over your career, how much of that is
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  Speaker 1: kind of a rinse and repeat type of checklist or
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  Speaker 1: do you have to go through each one and see that, Oh,
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  Speaker 1: this might have a little bit different approach to some
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  Speaker 1: of this checklists than the previous emerging technology that I've
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  Speaker 1: seen over the past decade.
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  Speaker 2: Yeah, I think it's a great question, and I think
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  Speaker 2: it really gets to the core of how do you
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  Speaker 2: define innovation. Many companies come out with new products, and
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  Speaker 2: those new products might have minor differentiation, somewhat incremental improvements
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  Speaker 2: over prior generations, and I would say those might fall
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  Speaker 2: into the rinse and repeat category that you described. But
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  Speaker 2: if you really step back and say we want to
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  Speaker 2: create something new, I would say every innovation of that
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  Speaker 2: magnitude is different from all others. Right, And so yes,
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  Speaker 2: there are fundamental checklists about pre clinical evidence, about safety, margins,
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  Speaker 2: about product market fit, and user interface ease of use.
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  Speaker 2: Those will characterize all innovations. But how those show up
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  Speaker 2: in the hands of a clinician in the delivery system
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  Speaker 2: and the workflow of the healthcare provider, those are often
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  Speaker 2: entirely different and so I would say on a continuum,
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  Speaker 2: the more innovative something is, the more likely it is
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  Speaker 2: to have its very own and unique checklist. And that's
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  Speaker 2: exactly what an experienced management team is focused on. How
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  Speaker 2: to define that, how to ultimately articulate the most capital
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  Speaker 2: efficient way to advance through that list, how to de
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  Speaker 2: risk it over time so that you have increasing probability
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  Speaker 2: of success with every turn of the month and of
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  Speaker 2: the of the quarter, and ultimately deliver the most capital
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  Speaker 2: efficient product to the to the end user and ultimately
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  Speaker 2: to patients. And so it's a it's a an exhilarating process.
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  Speaker 2: It's a challenging process. It's got clinical and regulatory and
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  Speaker 2: technology and scaling challenges at every step along the way.
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  Speaker 2: But that's really what makes healthcare advance. It's it's that
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  Speaker 2: effort to invest in innovation and run programs to deliver
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  Speaker 2: value while trying to minimize every day the chances of failure.
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  Speaker 1: Interesting. And so it's got a great segue into the
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  Speaker 1: development that you're doing with nanosecond PFA, and you know,
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  Speaker 1: we'll talk about some of these other applications that are
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  Speaker 1: in the pipeline, but you know, definitely PFA is the
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  Speaker 1: biggest headline, if not the biggest headline, one of the
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  Speaker 1: biggest head in medtech over the past eighteen months. And
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  Speaker 1: one of the things is that because there are a
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  Speaker 1: lot of PFA technology already in the market, Boston scientifics
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  Speaker 1: the leader right now. Metronic is, you know, a very
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  Speaker 1: close second at this point catching up. Jaja and Abbott
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  Speaker 1: are making developments. There's a lot of other private companies
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  Speaker 1: and they're already talking about the benefit of PFA to
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  Speaker 1: you know, that traditional thermo radio frequency, so you know
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  Speaker 1: and kund of with that, you know, the PFA they
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  Speaker 1: talk about, you know, limiting the heat to the damage
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  Speaker 1: to the extra tissue. How does nanosecond PFA be that
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  Speaker 1: even further step in that improvement from the traditional thermo RF.
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  Speaker 2: Yeah, well, it's a great point. And first of all,
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  Speaker 2: a couple of comments. Number one, I agree completely PFA.
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  Speaker 2: First of all, PFA is a more general term standing
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  Speaker 2: for pulse field deblation. But pulse field deblation's first commercial
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  Speaker 2: application is in atrial fibrillation, and that is the big
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  Speaker 2: market that you're referring to. So atrial fibrillation will start
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  Speaker 2: by just characterizing it briefly, it's it's the most common
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  Speaker 2: cardiac a rhythmia. It is diagnosed multiple million times a
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  Speaker 2: year in the United States. It's a it's a condition
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  Speaker 2: that gets worse over time and is frankly more readily
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  Speaker 2: diagnosed today because of the prevalence of apple watches and
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  Speaker 2: of wearable cardiac monitors that are quite discerning of cardiac
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  Speaker 2: rhythms and can tell a patient that they may have
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  Speaker 2: suspected a FIB. So that creates a big market, right
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  Speaker 2: that number. Nobody wants a heart problem, and this is
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  Speaker 2: the number one electrical disturbance of the heart. So a
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  Speaker 2: long come in the past a technology to turn off
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  Speaker 2: those A rhythmias by ablating the tissue that carries the
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  Speaker 2: aberrant signal. And that is exactly what you were referring
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  Speaker 2: to with respect to radio frequency ablation. So that's using heat,
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  Speaker 2: using the deposition of ultra high thermal energy to destroy
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  Speaker 2: tissue and turn off, effectively turn off that circuit of
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  Speaker 2: abnormal electrical conduction. But that brings downsides. It is time consuming,
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  Speaker 2: it is i'd say, very technique sensitive, and it uses
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  Speaker 2: excessive heat and that heat has to go somewhere, and
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  Speaker 2: so if it's carefully delivered in the heart, it will
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  Speaker 2: destroy tissue locally, but it also brings safety risks associated
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  Speaker 2: with how that heat may spread either within the heart
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  Speaker 2: or to other organs that are adjacent to the heart,
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  Speaker 2: and those are safety problems that have been a concern
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  Speaker 2: for radio frequency ablation for a long time. Boston Scientific
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  Speaker 2: was the first to introduce pulse field deblation, introducing first
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  Speaker 2: generation pulse electric fields measured in microseconds or millions of
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  Speaker 2: a second, which is in pulse electric fields, relatively slow
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  Speaker 2: durations kind of first gen. And despite being first gen,
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  Speaker 2: it has taken the market by storm. And I think
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  Speaker 2: the essential benefit is the replacement of thermal energy and
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  Speaker 2: heat destruction of tissue with an electrical field that can
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  Speaker 2: begin to cause a cell death without heat by tricking
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  Speaker 2: the cell into losing its structural integrity. And the cell
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  Speaker 2: in the end is held together by an electrical field,
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  Speaker 2: and so by overpowering that electrical field, we can create
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  Speaker 2: a permeability in cell membranes and that leads to the
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  Speaker 2: destruction of the cell. So it's a very novel concept,
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  Speaker 2: and because it has demonstrated to be equally effective to
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  Speaker 2: radio frequency and safer and potentially with an easier workflow
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  Speaker 2: including shorter procedure times. That has become a wave of
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  Speaker 2: success in a FIB and the market has converted to
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  Speaker 2: PFA first generation. So then the question is, as that
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  Speaker 2: has settled in, and as the market of electrophysiology has
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  Speaker 2: become hyper comfortable using pulse electric fields because of safety
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  Speaker 2: and shorter procedure times, how much of a benefit would
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  Speaker 2: be made available if a next generation pulse electric field
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  Speaker 2: energy using nanosecond PFA were to come along, that would
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  Speaker 2: further reduce procedure times dramatically, that would potentially enhance safety
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  Speaker 2: by further removing the electrical field from any kind of
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  Speaker 2: a thermal deposition, so very exquisitely non thermal that could
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  Speaker 2: potentially deposit energy so quickly as to dramatically improve the
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  Speaker 2: workflow of the procedure, and as we've now begun to
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  Speaker 2: see with long term results, could potentially improve clinical outcomes
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  Speaker 2: because the effectiveness of the lesion creation, the effectiveness of
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  Speaker 2: that nanosecond pulse electric field begins to look as if
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  Speaker 2: it is a step function ahead of first generation PFA.
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  Speaker 2: So that's what we think we have with nanosecond PFA,
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  Speaker 2: not only a second generation PFA, but as much of
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  Speaker 2: a gain in clinical perform potential as PFA was over
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  Speaker 2: RF and with with PFA Gen one, we saw it
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  Speaker 2: take over the market and they're they're because of that
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  Speaker 2: list of characteristics I just mentioned, there is reason to
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  Speaker 2: believe nanosecond PFA could do the same thing to the
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  Speaker 2: first gen PFA market as well.
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  Speaker 1: Interesting and then so just make sure that I understand
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  Speaker 1: that correctly. It's the it could be potentially more effective
• 15:29
  Speaker 1: because it's a shorter but a stronger and therefore a
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  Speaker 1: deeper penetration into the cell to create that leision further within,
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  Speaker 1: deeper into the tissue. Is that the right way to
• 15:41
  Speaker 1: think about that.
• 15:42
  Speaker 2: That is the right way to think about it, Matt.
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  Speaker 2: It is a it is a combination of two parameters
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  Speaker 2: that that we manage. One, as we've talked about, is
• 15:51
  Speaker 2: that ultra short pulse duration, which is, to think about it,
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  Speaker 2: a microsecond pulse used today commercially in a fib by
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  Speaker 2: one of the major players. Those pulses are measured in
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  Speaker 2: millions of a second, and then when we move to
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  Speaker 2: nanosecond PFA, we move to billions of a second. And
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  Speaker 2: there's not just a small difference between a millionth and
• 16:17
  Speaker 2: a billion, there's a thousandfold difference, right, a thousandfold difference
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  Speaker 2: between a million and a billion. So when you think
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  Speaker 2: about shortening pulse duration and moving to the nanosecond scale,
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  Speaker 2: you're really shortening that duration dramatically. Now we pair that
• 16:35
  Speaker 2: with an increase in that energy delivery, and so essentially
• 16:42
  Speaker 2: we're redefining the curve to be much taller and much tighter.
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  Speaker 2: And that height of that curve is really the amplitude
• 16:52
  Speaker 2: of the curve, which is another way of saying how
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  Speaker 2: much power exists to drive it into the tissue. So
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  Speaker 2: that unique combination is what we possess, and we find
• 17:04
  Speaker 2: that that delivers deeper lesions, much more consistent lesions, lesions
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  Speaker 2: in tissue that clearly leave behind treated zones, and that
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  Speaker 2: reduces the chance and practically eliminates the chance for recurrence.
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  Speaker 1: Right.
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  Speaker 2: So, because we're not just stunning any tissue, we're actually
• 17:29
  Speaker 2: treating that tissue and causing that tissue to enter a
• 17:34
  Speaker 2: phase of regulated cell death, from which of course cells
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  Speaker 2: cannot recover. And so what we're trying to do is
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  Speaker 2: deliver a definitive treatment that doesn't allow reconnection electrically. And
• 17:48
  Speaker 2: if we can do that safely and swiftly. Then we
• 17:52
  Speaker 2: have clearly the next generation therapy for atrial fibrillation.
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  Speaker 1: Definitely, And you know, it's funny, I'm gaining flashbacks from
• 17:59
  Speaker 1: my tenth grade physics class with the amplitudes and all
• 18:02
  Speaker 1: of that. But let's also just talk about then. You know,
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  Speaker 1: you have we have the technology for the catheter. How
• 18:09
  Speaker 1: is but with any ablation procedure, you have the catheter
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  Speaker 1: and you have the mapping component. So how will your
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  Speaker 1: catheter be designed to work with the mapping systems that
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  Speaker 1: are already in the market.
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  Speaker 2: Well, let me just say in addition to it, I
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  Speaker 2: completely agree with what you've said, but there are really
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  Speaker 2: three components. There's the catheter and the generator and the
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  Speaker 2: mapping component. And really the secret to our technology resides
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  Speaker 2: in the generator. The design of that those pulse parameters
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  Speaker 2: that create that nanosecond pulse electric field. Then that has
• 18:47
  Speaker 2: to be paired with a very specific catheter design to
• 18:50
  Speaker 2: take advantage of that unique pulse electric field. Those are
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  Speaker 2: two key components. And then the mapping system, of course,
• 18:58
  Speaker 2: is the third that you mentioned. And so first of all,
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  Speaker 2: mapping is used to place the cather, it's used to
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  Speaker 2: define for the electrophysiologist, where in the tissue are the
• 19:10
  Speaker 2: electrical currents going awry and where should you lay down
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  Speaker 2: your ablation lines to turn those aberrant ablation lines off.
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  Speaker 2: And so we're basically providing a therapeutic tool to closely
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  Speaker 2: follow those mapping outputs to allow the physician to precisely
• 19:34
  Speaker 2: deposit pulse electric field energy where it's desired in the
• 19:39
  Speaker 2: most effective locations to both deliver the most efficacious outcome
• 19:48
  Speaker 2: while damaging the least amount of cardiac tissue in the process.
• 19:52
  Speaker 2: So the goal is to have the ablation cath that
• 19:56
  Speaker 2: are talked to the mapping system so that the map
• 20:00
  Speaker 2: mapping system can accurately display where in the cardiac structure
• 20:05
  Speaker 2: that catheter resides and then tie in visually where the
• 20:11
  Speaker 2: catheter is relative to the anatomical target that the physician
• 20:15
  Speaker 2: is trying to ablate. Where is it within the left atrium,
• 20:18
  Speaker 2: where is it within the pulmonary vein, or which pulmonary
• 20:22
  Speaker 2: vein are you in, how do you want to move
• 20:24
  Speaker 2: from one vein to another? And are there other parts
• 20:27
  Speaker 2: of the left atrial structure that you want to ablate
• 20:29
  Speaker 2: based on the electrical mapping. So that's the mapping system,
• 20:33
  Speaker 2: and our catheter talks to that mapping system. It has
• 20:36
  Speaker 2: sensors built in that allow it to be delivering electro
• 20:43
  Speaker 2: cardiogram information and basically GPS information. It tells that system
• 20:53
  Speaker 2: where the catheter is within the cardiac structure, so the
• 20:57
  Speaker 2: physician can deliver that catheter exactly actly where he or
• 21:00
  Speaker 2: she wants it to be and then deliver ablation energy.
• 21:05
  Speaker 1: That's interesting with the mapping component, we'll cut. My attention
• 21:08
  Speaker 1: is the generator part seems to be the differentiated technology
• 21:14
  Speaker 1: in this case, and so what is the pattern kind
• 21:18
  Speaker 1: of portfolio for the catheter but also as well for
• 21:22
  Speaker 1: the generator and for nanosecond pulset build theblation in the
• 21:27
  Speaker 1: first place.
• 21:28
  Speaker 2: Yes, so patents play a very important part of our
• 21:31
  Speaker 2: company story, and of course in the medical technology world,
• 21:35
  Speaker 2: patents are very commonly sought and and every company lays
• 21:41
  Speaker 2: claim to some intellectual property. We have what I found
• 21:46
  Speaker 2: in my earliest days working with Pulse to be I
• 21:49
  Speaker 2: think the most compelling intellectual property estate of any company
• 21:53
  Speaker 2: of this scale, with multiple hundreds of patents already in
• 21:59
  Speaker 2: our possession. Those patents cover all facets of either the
• 22:04
  Speaker 2: creation or delivery of these unique pulses from the generator
• 22:09
  Speaker 2: through all of the connectors out to a device, whether
• 22:14
  Speaker 2: it's a catheter or a surgical tool, and then down
• 22:18
  Speaker 2: through the various elements of that device to the distal end,
• 22:22
  Speaker 2: the working end, where the electrodes actually work in tandem
• 22:29
  Speaker 2: to create that bipolar nanosecond pulse electric field. So it
• 22:34
  Speaker 2: is because we're delivering unique parameters of electricity in the
• 22:40
  Speaker 2: form of ultrashort duration and ultra high amplitude, that unique
• 22:46
  Speaker 2: combination has not historically been delivered into the body and
• 22:51
  Speaker 2: is challenging to do. And therefore, at every juncture where
• 22:56
  Speaker 2: unique technology is required to deliver that unique pulse electric field,
• 23:02
  Speaker 2: that created an intellectual property target, and so we ended
• 23:08
  Speaker 2: up being able to create intellectual property estates at covering
• 23:14
  Speaker 2: many facets of the creation and delivery of nanosecond high
• 23:20
  Speaker 2: voltage pulse electric fields, and that we believe places pulse
• 23:26
  Speaker 2: in a very unique and proprietary position with this energy
• 23:30
  Speaker 2: that will allow us to be the sole proprietor of
• 23:34
  Speaker 2: this technology for the foreseeable future.
• 23:38
  Speaker 1: It's always good to have that moat with your pen
• 23:41
  Speaker 1: and protection there, and so then the other thing though,
• 23:43
  Speaker 1: as well, is you need to have that clinical data.
• 23:47
  Speaker 1: And so you know, you just recently published your first
• 23:51
  Speaker 1: and human study at af symposium a couple months ago. Now,
• 23:56
  Speaker 1: what were some of the highlights or the key takeaways
• 23:58
  Speaker 1: that you got you you know, took away from the presentation.
• 24:04
  Speaker 1: Was there any surprises that you saw? Was this like,
• 24:07
  Speaker 1: this is what we expected and this is what we got.
• 24:11
  Speaker 2: Well, it's it's fine to have expectations, but we all
• 24:14
  Speaker 2: need to validate our expectations and it is through that
• 24:18
  Speaker 2: validation that others can begin to have the same conviction
• 24:21
  Speaker 2: about our technology as we have it within the Pulse team.
• 24:24
  Speaker 2: So that evidence is key. I would say a couple
• 24:27
  Speaker 2: of things to that, Matt. First of all, there are
• 24:30
  Speaker 2: there are probably two really important areas of breakthrough evidence.
• 24:35
  Speaker 2: The first one we had we had begun to see
• 24:38
  Speaker 2: early early on, because it's about acute performance. What happens
• 24:42
  Speaker 2: in the procedure. How swiftly can we deliver therapy? How
• 24:47
  Speaker 2: few lesions do we need to deliver in order to
• 24:52
  Speaker 2: create an effective outcome? How is that workflow translating to
• 24:58
  Speaker 2: patient throughput, to procedure time, to catheter dwell time, to
• 25:03
  Speaker 2: the number of oblations, to the total amount of time
• 25:08
  Speaker 2: from the first to the last oblation. Those measures of
• 25:12
  Speaker 2: acute procedural performance we began to see early on in
• 25:16
  Speaker 2: our experience, and those measures are superior to what is
• 25:20
  Speaker 2: available today with any other catheter system. Now, importantly, in
• 25:25
  Speaker 2: the history of the transition from radio frequency to first
• 25:29
  Speaker 2: generation PFA to today, the only real benefit has been
• 25:34
  Speaker 2: in speed, workflow, and safety. There has been no demonstrated
• 25:41
  Speaker 2: efficacy benefit so on the parameters that have so far
• 25:46
  Speaker 2: defined market share leadership in a fib therapy. It was
• 25:50
  Speaker 2: becoming apparent that the pulse system could deliver superior performance,
• 25:57
  Speaker 2: but it wasn't until we announced our data following patients
• 26:02
  Speaker 2: a full twelve months and measuring them according to the
• 26:07
  Speaker 2: endpoint that will be used in a clinical study an
• 26:12
  Speaker 2: ID a pivotal trial regulated by the FDA. It wasn't
• 26:17
  Speaker 2: until we started to see those twelve month outcomes that
• 26:20
  Speaker 2: we could really confirm that we had the potential for
• 26:25
  Speaker 2: the first time, really in the history of this space
• 26:28
  Speaker 2: of a fhibiblation to combine superior workflow and speed with
• 26:33
  Speaker 2: superior efficacy. And so the efficacy that we will talk
• 26:37
  Speaker 2: about is freedom from atrial fibrillation. Right, That's what you want.
• 26:42
  Speaker 2: You want to treat a patient on day one and
• 26:45
  Speaker 2: on day three hundred and sixty five, you want to
• 26:47
  Speaker 2: test to see does that patient have any a FIB.
• 26:50
  Speaker 2: Have they needed to go back on drugs that control arrhythmias,
• 26:56
  Speaker 2: Have they needed a pacemaker to control their rhythm? If
• 27:01
  Speaker 2: none of those things have happened, that's a successful treatment,
• 27:04
  Speaker 2: and success historically in a FIB intervention is defined in
• 27:09
  Speaker 2: the range of seventy five percent or so, which is
• 27:13
  Speaker 2: to say, one year freedom from a FIB off drugs.
• 27:18
  Speaker 2: And so when we published not seventy five percent but
• 27:22
  Speaker 2: ninety six percent, I believe that number really caused the
• 27:30
  Speaker 2: electrophysiology community to take notice. That is a number that
• 27:34
  Speaker 2: has simply never been approached by any study, any technology,
• 27:39
  Speaker 2: any protocol, and has to be related to a new
• 27:44
  Speaker 2: therapeutic benefit of being delivered in the cardiac tissue by
• 27:48
  Speaker 2: this nanosecond PFA. So I'd say that number, that ninety
• 27:52
  Speaker 2: six percent procedural success number. And then a second number
• 27:57
  Speaker 2: which was broader, which was freedom from all atrial arrhythmias,
• 28:01
  Speaker 2: freedom from atrial tachycardia, from atrial flutter, from atrial fibrillation,
• 28:08
  Speaker 2: not just at day three sixty five, but at any
• 28:11
  Speaker 2: point along the way, measured by multiple measurements taken throughout
• 28:16
  Speaker 2: the course of that year, even that number was ninety percent.
• 28:21
  Speaker 2: And again that number is unprecedented. So I'd say those
• 28:24
  Speaker 2: two numbers coming out, as you described at the APHIB
• 28:27
  Speaker 2: symposium in February, were really the telltale indicators that Pulse
• 28:33
  Speaker 2: Biosciences NSPFA was looking to be and starting to be
• 28:40
  Speaker 2: validated as a definitively different and potentially superior therapy in
• 28:46
  Speaker 2: this very large market.
• 28:47
  Speaker 1: Yeah. No, that ninety percent freedom from a fib and
• 28:51
  Speaker 1: the other arrhythmias versus kind of what I'm seen in
• 28:54
  Speaker 1: the past being seventy sometimes you get up to eighty
• 28:57
  Speaker 1: percent almost is meaningful. I feel like there's also some
• 29:00
  Speaker 1: other data that was interesting. I'm curious what your thoughts are.
• 29:03
  Speaker 1: When was the three month PVI durability data. The other
• 29:08
  Speaker 1: one that I saw was that this this cohort is
• 29:11
  Speaker 1: split out between a five second cohort and a two
• 29:15
  Speaker 1: and a half second coord So what is that and
• 29:17
  Speaker 1: what is that? How is that important to maybe apply
• 29:20
  Speaker 1: this nanosecond technology in the future.
• 29:23
  Speaker 2: Yes, very good question. So on the on the on
• 29:28
  Speaker 2: the first point, what we're really dealing with there, Well,
• 29:32
  Speaker 2: let me deal with the five second first, because five
• 29:34
  Speaker 2: second is our therapy. We started with five second, and
• 29:40
  Speaker 2: we were getting extremely clear and compelling clinical evidence of success,
• 29:49
  Speaker 2: most importantly by that exact measure that you talked about.
• 29:53
  Speaker 2: The other point, which is the three month remapping, and
• 29:58
  Speaker 2: that's the most acute measure of cardiac tissue. And so
• 30:05
  Speaker 2: by remapping, which requires an interventional procedure, right, you have
• 30:08
  Speaker 2: to bring the patient back, you have to perform a
• 30:12
  Speaker 2: percutaneous intervention, and you have to put a high density
• 30:16
  Speaker 2: mapping catheter into the heart. So it's not done commonly,
• 30:20
  Speaker 2: but it is done within clinical trials. The five second
• 30:25
  Speaker 2: excuse me ablation duration look to be extremely effective in
• 30:30
  Speaker 2: that process. Along the way, as part of our clinical strategy,
• 30:36
  Speaker 2: we asked the question if even though we did a
• 30:40
  Speaker 2: lot of pre clinical work to select five second, as
• 30:43
  Speaker 2: effective as it was, it's always important to ask the question,
• 30:47
  Speaker 2: is that the lowest effective dose or is it possible
• 30:51
  Speaker 2: to lower the dose and still achieve the same clinical endpoint.
• 30:56
  Speaker 2: So we ran a small cohort in parallel of thirty
• 31:00
  Speaker 2: six patients at a reduced dose two point five seconds
• 31:05
  Speaker 2: versus five and did that same invasive measure of three
• 31:12
  Speaker 2: month remapping, and we saw that while that standalone two
• 31:17
  Speaker 2: point five second data would have been the best data
• 31:20
  Speaker 2: ever in the field of a FIB, it wasn't as
• 31:23
  Speaker 2: good as the five second So we felt we could
• 31:27
  Speaker 2: conclude from that evidence that the five second dose was
• 31:31
  Speaker 2: a low effective dose, and we terminated use of the
• 31:34
  Speaker 2: two point five second dose thereafter. Now back to the
• 31:40
  Speaker 2: question about remapping, that three month PBI data is really
• 31:46
  Speaker 2: more acutely sensitive even then symptoms, right, we ask a
• 31:51
  Speaker 2: patient do you have a FIB, and we put monitors
• 31:56
  Speaker 2: on their chest so that if they feel in arrhythmia
• 31:59
  Speaker 2: they can press a button and do a recording of it.
• 32:02
  Speaker 2: And then at the end of a year we have
• 32:04
  Speaker 2: them wear a Whulter monitor and we look for and
• 32:08
  Speaker 2: detect a FIB. But there could be lower levels of
• 32:13
  Speaker 2: a arrhythmias that are present that the patient can't feel,
• 32:17
  Speaker 2: that are yet asymptomatic, and so nothing will detect those
• 32:22
  Speaker 2: as accurately as an invasive remapping, and that is done
• 32:27
  Speaker 2: in protocols at the ninety day period. So those data
• 32:32
  Speaker 2: for pulse look fantastic, but that's not real world, right,
• 32:36
  Speaker 2: because you can find something that is electrically noticeable, but
• 32:42
  Speaker 2: the patient might never ever feel it and it might
• 32:45
  Speaker 2: never lead to anything. So you have to be careful
• 32:48
  Speaker 2: not to over react to what you might find on
• 32:52
  Speaker 2: a remapping case because it can lead to the desire
• 32:56
  Speaker 2: to ablate again, even though the electrical trace that might
• 33:02
  Speaker 2: be treated uh ends up not being symptomatic at all.
• 33:06
  Speaker 2: So the remapping data very interesting, validating fantastic results and
• 33:13
  Speaker 2: supplementing really our long term clinical outcomes that really form
• 33:18
  Speaker 2: the headline for our story.
• 33:20
  Speaker 1: Okay, And so you know, this is, like I said,
• 33:22
  Speaker 1: very compelling data that came out from the af symposium.
• 33:26
  Speaker 1: You know, as we were talking about, you know, checking
• 33:28
  Speaker 1: off the checklists, you know, what what is next for
• 33:33
  Speaker 1: nanosecond PFA and then kind of in that timeline, have
• 33:38
  Speaker 1: you provided any comments about the end of the timeline,
• 33:42
  Speaker 1: like when you expect potential FDA approval and commercial launch.
• 33:47
  Speaker 2: Yes, yes we have, and I'll describe that for you.
• 33:50
  Speaker 2: So what's next in the timeline is really the the
• 33:54
  Speaker 2: initiation of and the completion of our ide So we
• 34:00
  Speaker 2: received FDA approval to commence our pivotal study at the
• 34:04
  Speaker 2: very end of the fourth quarter in December of twenty five,
• 34:09
  Speaker 2: and we initiated work with our clinical trial sites in
• 34:14
  Speaker 2: Q one and as we announced actually just a few
• 34:18
  Speaker 2: days ago, we have now enrolled the first patients into
• 34:23
  Speaker 2: this study at Saint Bernard's Hospital in Jonesboro, Arkansas. Doctor
• 34:30
  Speaker 2: deb Nayer was the first to enroll in this pivotal
• 34:35
  Speaker 2: study and very prominent study, and we're delighted to have
• 34:39
  Speaker 2: her lead us off in enrollment and on her first
• 34:45
  Speaker 2: day she enrolled seven patients, which is I think further
• 34:49
  Speaker 2: evidence of the workflow advantages. Right, So if you think
• 34:53
  Speaker 2: about taking a catheter that has never been used in
• 34:57
  Speaker 2: this hospital before so seamlessly fitting into their workflow that
• 35:05
  Speaker 2: they could do seven cases with a brand new technology
• 35:11
  Speaker 2: on the first day, that to me is remarkable in
• 35:14
  Speaker 2: and of itself. The goal of the ide of course,
• 35:18
  Speaker 2: is to validate the same type of clinical outcome that
• 35:23
  Speaker 2: we showed coming from our very large European feasibility study,
• 35:28
  Speaker 2: representing represented by the data that we presented at the afsymposium.
• 35:33
  Speaker 2: So if we take those general targets of results, including
• 35:40
  Speaker 2: the ninety percent freedom from hrial arrhythmia as an example,
• 35:44
  Speaker 2: and we were to validate those in the ide then
• 35:47
  Speaker 2: of course we would have truly groundbreaking clinical outcomes, and
• 35:53
  Speaker 2: that's what we're aiming for. That's what we're running. The
• 35:56
  Speaker 2: study is designed as a single arm study to enroll
• 36:00
  Speaker 2: approximately one hundred and fifty five patients in up to
• 36:03
  Speaker 2: thirty centers principally in the US, although several centers from
• 36:08
  Speaker 2: outside the United States may be included. And we have
• 36:13
  Speaker 2: told those who are following our story that we expect
• 36:17
  Speaker 2: to We expected to commence enrollment in Q two, which
• 36:22
  Speaker 2: of course we have done here in the second week
• 36:24
  Speaker 2: of April, and we expect to complete enrollment by the
• 36:28
  Speaker 2: end of the year, with a goal of course internally
• 36:31
  Speaker 2: to try to do better than that if possible.
• 36:35
  Speaker 1: Interesting, and then you know, if I do my math right,
• 36:39
  Speaker 1: enrollment ends, let's say end of twenty twenty six, twelve
• 36:43
  Speaker 1: month primary endpoints for freedom of af and other arrhythmias
• 36:50
  Speaker 1: that gets to end of twenty twenty seven, gets presented
• 36:52
  Speaker 1: at ACC RHRS in twenty twenty eight. That looks sounds
• 36:56
  Speaker 1: like a mid to second half twenty.
• 36:58
  Speaker 2: So let's go through that, Matt. Yeah, because there's a
• 37:02
  Speaker 2: refinement to our follow up period that is unique to
• 37:05
  Speaker 2: this study interesting and that will actually shorten that timeline,
• 37:10
  Speaker 2: and so we're using primarily a six month endpoint, enriched
• 37:15
  Speaker 2: by some patients reaching twelve. And so we will follow
• 37:20
  Speaker 2: our first patients out a year, but our last patients
• 37:24
  Speaker 2: will only be followed six months. And so the way
• 37:28
  Speaker 2: to calculate the likely timeline is to take the last
• 37:31
  Speaker 2: patient in whenever that is occurring in the second half
• 37:38
  Speaker 2: of twenty twenty six, and then add six months to
• 37:43
  Speaker 2: that timeline to get call at the long pole in
• 37:47
  Speaker 2: the tent. So the goal here is to blend outcomes
• 37:51
  Speaker 2: from some patients monitored twelve other patients monitored six, to
• 37:58
  Speaker 2: use the twelve month data on those first patients to
• 38:02
  Speaker 2: enrich and analyze the probability of how those latter patients
• 38:09
  Speaker 2: monitored to six months would do at twelve and put
• 38:12
  Speaker 2: that together with a complex statistical analysis called a Bayesian
• 38:17
  Speaker 2: analysis to ultimately land on an aggregate follow up time
• 38:21
  Speaker 2: that will be shorter than twelve months for the total population.
• 38:26
  Speaker 2: That then leads to a likely data package not at
• 38:34
  Speaker 2: the end of twenty seven, but somewhere earlier in the
• 38:37
  Speaker 2: second half of twenty seven, and then that can lead
• 38:41
  Speaker 2: to with a presumed one hundred and eighty day PMA
• 38:45
  Speaker 2: approval time to a PMA clearance in early twenty twenty eight.
• 38:52
  Speaker 1: Interesting, that's good to know be able to follow that
• 38:56
  Speaker 1: on our clinical catalyst chart here. Maybe just to close
• 39:01
  Speaker 1: out then, you know, we had you know, we talked
• 39:05
  Speaker 1: a lot about the polsfieldiblation, but there's a lot of
• 39:07
  Speaker 1: other clinical applications. We talked about the thyroid application for
• 39:11
  Speaker 1: it too, and then just kind of squeezing in there.
• 39:14
  Speaker 1: I mean, you have all these children. We talked a
• 39:17
  Speaker 1: lot about PFA. It's tough to choose which one's your
• 39:20
  Speaker 1: favorite child overall. But we're also dealing with you know,
• 39:24
  Speaker 1: as a publicly traded company, if I saw it correctly,
• 39:27
  Speaker 1: as of the end of December, had eighty million in
• 39:30
  Speaker 1: cash available, putting on your CEO and your financing hat.
• 39:35
  Speaker 1: How do you allocate these resources over the next twelve
• 39:38
  Speaker 1: months or so to be able to get these products
• 39:40
  Speaker 1: out getting commercialized, but also being able to be aware
• 39:44
  Speaker 1: of that cash balance.
• 39:46
  Speaker 2: Right, Well, thank you for the question. It's a great question,
• 39:49
  Speaker 2: and it's exactly how we think about things. We love
• 39:52
  Speaker 2: all our children equally, but that doesn't mean that they
• 39:56
  Speaker 2: all have the exact same potential, and so in the
• 39:59
  Speaker 2: past we announced that we would be in response to
• 40:04
  Speaker 2: the compelling data that were presented at the afsymposium and
• 40:10
  Speaker 2: in light of the magnitude of that market and the
• 40:13
  Speaker 2: impact that our technology could have on such a large scale,
• 40:18
  Speaker 2: both as it relates to a multi billion dollar existing
• 40:21
  Speaker 2: a FIB market over a three billion dollar a blation
• 40:26
  Speaker 2: catheter market in the United States in twenty twenty six,
• 40:30
  Speaker 2: procedural growth exceeding twenty percent. So that is one of
• 40:35
  Speaker 2: the most exciting medical technology markets on the globe, and
• 40:40
  Speaker 2: that's a market that our data looked to have the
• 40:43
  Speaker 2: potential to be very disruptive within. So if you look
• 40:46
  Speaker 2: at the magnitude of impact in AFIB and the quality
• 40:53
  Speaker 2: of the data that we've produced thus far and the
• 40:55
  Speaker 2: speed to value creation, we determine that that needed to
• 41:01
  Speaker 2: then become our highest priority. So across the span of
• 41:05
  Speaker 2: very compelling clinical opportunities, we said as a board that
• 41:11
  Speaker 2: the AFIB opportunity must become number one, and so we
• 41:17
  Speaker 2: have begun to shift some of our resources toward that direction,
• 41:21
  Speaker 2: all with the goal of pulling forward timelines on clinical
• 41:25
  Speaker 2: trials follow on clinical studies that will generate additional data sets,
• 41:31
  Speaker 2: advancing at a faster rate next generation technology and product development,
• 41:37
  Speaker 2: things that we know we can impact with slightly increased resources. Now,
• 41:42
  Speaker 2: in addition to that, we do have our initial clearance
• 41:47
  Speaker 2: in soft tissue applications and are targeting in that first
• 41:52
  Speaker 2: application the treatment of benign thybroid nodules as our first
• 41:58
  Speaker 2: clinical use case. I will say back to the children analogy,
• 42:04
  Speaker 2: the clinical data that we've generated for the benefit of
• 42:09
  Speaker 2: patients with benign thyroid nodules is as compelling as are
• 42:13
  Speaker 2: a FIB data, but the market is smaller and the
• 42:16
  Speaker 2: market is not present and tangible because it's not developed
• 42:22
  Speaker 2: in the form of a high volume, minimally invasive treatment paradigm.
• 42:28
  Speaker 2: It's a market that is predominantly addressed with thyroid removal
• 42:33
  Speaker 2: through surgery. Now, because thiroids are removed surgically, we have
• 42:38
  Speaker 2: the potential to really alter patient lives by making nanosecond
• 42:43
  Speaker 2: PFA available for benign thiroid nodules. However, we have to
• 42:47
  Speaker 2: recognize that that is a market development program, and so
• 42:51
  Speaker 2: those resources we are applying to that opportunity are in
• 42:54
  Speaker 2: the market development realm focused on improving the volume and
• 43:00
  Speaker 2: diversity of clinical evidence, expanding our clinical indication with the FDA,
• 43:06
  Speaker 2: and ultimately generating evidence that will facilitate payment and reimbursement
• 43:11
  Speaker 2: from commercial payers for that young patient population. So that's
• 43:15
  Speaker 2: what we're doing with our first commercial indication focused on
• 43:20
  Speaker 2: the thyroid. But most importantly is the message that is
• 43:24
  Speaker 2: implied in your question, which is that we are very
• 43:27
  Speaker 2: focused on APHIB and the number one job right now
• 43:31
  Speaker 2: for a FIB is to drive quality enrollment and outstanding
• 43:36
  Speaker 2: data collection in the Nanopulse APHIB study, which is now
• 43:42
  Speaker 2: up and running and will be expanding obviously across multiple
• 43:46
  Speaker 2: centers and enrolling at a faster rate over the course
• 43:50
  Speaker 2: of Q two and Q three.
• 43:53
  Speaker 1: Fascinating. I'm very excited to watch how this technology develops
• 43:57
  Speaker 1: for treatment of a FIB, given the size of its mark.
• 44:01
  Speaker 1: But Paul, thank you for joining us today. What an
• 44:02
  Speaker 1: excellent story.
• 44:03
  Speaker 2: Matt. I'm honored to have been selected for participation in
• 44:08
  Speaker 2: your program and I appreciate your great questions and thank
• 44:12
  Speaker 2: you for hosting.
• 44:13
  Speaker 1: Me absolutely, and thank you to our producers at Didya
• 44:17
  Speaker 1: Samani and Mariam Waile for all the behind the scene work,
• 44:21
  Speaker 1: and thank you to our listeners for tuning in today.
• 44:23
  Speaker 1: We hope you join us for future episodes, and if
• 44:26
  Speaker 1: you'd like to stay up to date, you can click
• 44:27
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• 44:31
  Speaker 1: Take care, SASO,