# Ceryx Medical: company uses bioelectronics to coordinate the heart and lungs

An episode of [Physics World Weekly Podcast](https://invisiblenetwork.ai/podcast/1400686733), 16 Jan 2025, 42 min.

Audio: https://media.blubrry.com/physicsworldweeklypodcast/content.blubrry.com/physicsworldweeklypodcast/PWWeekly16January2024CeryxMedical.mp3

Biomedical engineer Stuart Plant and physicist Ashok Chauhan are our podcast guests

## Transcript

[0:07] Hello, and welcome to the Physics World Weekly
[0:10] podcast.
[0:11] Heart failure is a serious condition
[0:14] in which a damaged heart
[0:16] loses its ability to pump blood around the
[0:19] body.
[0:21] The damage usually gets progressively
[0:23] worse
[0:24] so that 5 years after a diagnosis,
[0:27] about 50%
[0:29] of patients
[0:30] with heart failure will be dead.
[0:33] The disease affects as many as a 100,000,000
[0:37] people
[0:38] worldwide.
[0:39] And in the UK,
[0:40] about 1 to 2 percent of the National
[0:43] Health Service budget is spent on managing the
[0:47] disease,
[0:48] with most of the expenditure
[0:50] related to hospitalization.
[0:53] So it's not surprising that scientists
[0:56] are looking for new ways to improve the
[0:59] outlook for people with heart failure
[1:01] and perhaps even cure the disease.
[1:05] This podcast features the biomedical
[1:08] engineer,
[1:09] Stuart Plant,
[1:10] and the physicist,
[1:12] Ashok
[1:12] Chowhin,
[1:14] who work for Sirix Medical,
[1:16] a UK based company that's developed a bioelectronic
[1:21] system that helps patients with heart failure.
[1:25] Stewart is the company's CEO,
[1:28] and Ashok
[1:29] is its senior scientist.
[1:32] Here they are in conversation
[1:34] with Physics World's Margaret Harris.
[1:37] As well as chatting about the company's work
[1:39] on treating heart failure,
[1:41] Ashok and Stewart also talk about other applications
[1:45] of bioelectronics
[1:47] and the challenges and rewards
[1:50] of developing
[1:51] medical technologies
[1:52] within a small company.
[2:02] Okay. So
[2:03] first question, Stuart.
[2:05] What medical problem is CERiX trying to address
[2:08] here?
[2:10] Well, the first,
[2:11] medical problem we're looking to address, and there
[2:13] are actually multiple
[2:15] applications
[2:15] for our technology. But in the first instance,
[2:18] we're looking at a disease called
[2:20] called heart failure.
[2:22] Now heart failure occurs when you've had,
[2:25] you know, heart attack, you've had chronic hypertension.
[2:28] Maybe, you know, these days you have to
[2:29] think about COVID
[2:31] and infections that that can affect the the
[2:33] muscle of the of the heart. But basically
[2:36] some incident has caused caused damage to the
[2:38] heart and the muscle
[2:40] has been has been damaged. Some of it
[2:42] may have died. Some of it has become
[2:44] dysfunctional
[2:45] or at least immobile,
[2:47] but your heart basically can't work as, as
[2:49] well as it, as it once did.
[2:52] So it means that it's not supplying as
[2:54] much blood to the body
[2:56] and your body doesn't like this. So it
[2:58] kind of
[3:00] activates various compensatory mechanisms. It will push your
[3:03] blood pressure up and increase the volume of,
[3:05] of, of fluid basically
[3:08] in your body. And it will cause your
[3:10] heart to beat harder and it will cause
[3:11] it to be beat faster.
[3:14] Now this is one of the nature's quite
[3:16] good at these types of mechanisms. And it
[3:18] does, it does provide compensation for that decrease
[3:21] in cardiac output from the, from the damaged,
[3:23] damaged heart. So it is kind of restoring
[3:25] its blood supply. But now you've got a
[3:27] heart which is damaged already, which has been
[3:29] made to work harder.
[3:31] And as with any muscle, if you don't
[3:33] rest it, once it's been damaged, the the
[3:35] injury just gets worse.
[3:36] So heart failure occurs when the body reacts
[3:38] to this initial initial injury
[3:41] and drives the heart on. And then over
[3:43] a period of time, that injury just gets
[3:45] worse and worse and worse. And the structure
[3:47] of the heart becomes
[3:48] more abnormal
[3:49] and the function of the heart just becomes
[3:51] poorer and poorer. And what this means for
[3:53] patients is that eventually they start to experience
[3:56] feelings of breathlessness. They can't exercise in the
[3:59] way that they once they once did. But
[4:01] as the heart gets worse and worse, eventually
[4:03] you can't even get out of a chair.
[4:04] Making a cup of tea becomes exhausting exhausting.
[4:08] And ultimately, these patients, you know, they end
[4:10] up on oxygen 24 hours a day. They
[4:12] end up in bed.
[4:13] They end up in hospice care. And then
[4:15] unless they get something extreme like a heart
[4:17] transplant or maybe a,
[4:21] an LVAD heart pump device,
[4:23] ultimately, they'll they'll sadly, they'll die.
[4:26] So at the moment, there's about, you know,
[4:28] if, I mean, if you Google it, it's
[4:30] it says that there's about 30,000,000
[4:32] people in the world with with heart failure.
[4:34] That's a bit of a European
[4:36] US centric
[4:37] number, right, I'd say. I mean, on average,
[4:39] there's about 2% of the adult population has
[4:41] heart failure. So it's probably more like a
[4:43] 100,000,000 people worldwide
[4:45] currently have heart failure.
[4:47] And the survival rates for these patients are
[4:49] pretty poor. So on average,
[4:52] 5 years after diagnosis, 50% of the patients
[4:54] with heart failure
[4:56] will be dead. And in fact, in the
[4:58] 1st year, 30% will will probably die
[5:01] after the initial diagnosis.
[5:04] Moment the, you know, medications are directed towards,
[5:08] you know, trying to control the symptoms of
[5:09] heart failure. So they'll try and, you know,
[5:14] give you a better quality of life, improve
[5:16] your exercise tolerance. And a lot of them
[5:18] are trying to, you know, maybe slow the
[5:21] heart down. They give you beta blockers, slow
[5:22] the heart down. They'll give you ACE inhibitors,
[5:24] dilate your blood vessels. And that's trying to
[5:25] relieve the strain on the heart. So trying
[5:27] to release the extra strain on the heart
[5:29] and try and prolong
[5:31] the, the lifespan of the, of the heart
[5:32] itself. But they're not really getting to the
[5:34] core of the disease itself and trying to,
[5:37] trying to treat
[5:38] and basically reverse and cure this disease.
[5:41] And that's why Ceryx is, is a, is
[5:42] a bit different.
[5:44] So you've talked a little bit about what
[5:46] the existing treatment is in terms of oxygen,
[5:48] ultimately a heart transplant or a physical device
[5:51] to help the heart continue to beat.
[5:53] How is Ceryx's technology different from that? How
[5:56] is your solution different from that, I should
[5:58] say?
[5:59] Well, CERECS came to this problem, I I
[6:02] suppose in a bit of a convoluted way,
[6:04] really, to be honest. I mean,
[6:07] I I I we're 2 academic founders. 1
[6:09] was a cardiac physiologist in Bristol, and he
[6:12] was studying a phenomenon
[6:13] called respiratory sinus arrhythmia.
[6:16] Now this is a natural synchronisation between the
[6:18] heart and the lungs. Your heart and the
[6:20] lungs are linked. So that when we're, when
[6:22] their system's healthy, they'll work together to optimise
[6:25] the performance of both of those organs. And
[6:27] put simply, when we, when we breathe in
[6:29] our hearts accelerate, our heart rate goes up
[6:32] very slightly. And when we breathe out, our
[6:33] heart rate goes down very slightly.
[6:36] Now it'd been known for us, you know,
[6:37] it's a couple of 100 years since this
[6:39] phenomenon was first identified, but no one really
[6:41] examined as to why, why the body would
[6:43] bother to do this.
[6:44] More recently in the, you know, the recent
[6:47] decades, people have started to look at why
[6:50] this phenomenon occurs and have discovered that it
[6:52] actually brings quite a lot of benefits to
[6:54] both organs.
[6:55] So most obviously, you know, when we breathe
[6:57] in our lungs fill with oxygen, so our
[6:59] heart accelerates to to to pump as much
[7:01] blood as possible around the lungs to aid
[7:03] with the gas exchange.
[7:05] Also, you know, our lungs are in our
[7:06] chest. When we breathe in, we lower the
[7:08] pressure in our chest to allow the air
[7:10] into our lungs. Of course, our heart is
[7:11] in our chest as well. So now the
[7:13] heart's in beating the lower pressure environment, so
[7:15] it takes less energy for the, for the,
[7:17] for the heart to be.
[7:19] And now there's a growing body of evidence
[7:21] in the literature around, you know, the all
[7:23] these little benefits that RSA bring to their
[7:26] cardiovascular assist, cardio respiration.
[7:29] Now Julian was looking at well, he was
[7:31] looking at this phenomenon in itself and he
[7:33] was also looking at the
[7:35] we have this RSA when we're young and
[7:37] healthy and we it's enhanced in athletes. It's
[7:40] also present in all vertebrae animals. So even,
[7:42] you know, even fish display some RSA type
[7:46] mechanism.
[7:47] You know, so that when we get diseases
[7:50] like heart failure, you lose this, this RSA
[7:52] mechanism, the synchronisation between the heart and the
[7:55] lungs. So Julian's hypothesis was,
[7:58] if you could put RSA back into patients
[8:00] with RSA, would it restore the benefits of
[8:02] this mechanism and could that potentially be therapeutic?
[8:05] And the problem Julian has was that restoring
[8:08] this link is actually bit of a more
[8:10] of a complicated problem than it than it
[8:12] might first appear.
[8:13] But fortunately, he
[8:16] he kind of received an email from a
[8:18] physicist at at Bath University,
[8:20] who is looking at synchronization between nonlinear oscillating
[8:24] systems.
[8:25] Now
[8:26] where you get a lot of nonlinearity
[8:29] is in is in biology. Biology seems to
[8:32] love nonlinearity.
[8:33] So although it's not a natural place for
[8:35] maybe a physicist to be looking, they they
[8:37] tended to look towards biology and looked at
[8:39] things like your legs. Your legs to a
[8:42] physicist in in in in their field would
[8:45] is just, are just a couple of oscillators.
[8:47] Not linear oscillator, like, but it's keeping synch,
[8:49] allow us to walk and then to run.
[8:51] And how is the body able to to
[8:53] do that? How are we able to change
[8:55] our gait? How are we able to go
[8:56] from walking to running, trip on a stick,
[8:58] and actually not fall over? And I suppose
[9:00] it is is an interesting physics problem.
[9:03] So So the physicist in question was Alan
[9:05] Nogaret at Bath and he had, you know,
[9:07] been studying this for some time and had
[9:09] come up with,
[9:11] basically,
[9:11] a paper, an electronic representation
[9:14] of the MEC control systems that the body
[9:16] uses to control these nonlinear oscillators.
[9:19] And now he had these devices and he
[9:21] sent out a blanket email, I think, to
[9:23] Bath and Bristol University saying, I've got this
[9:25] technology. Does anybody have any ideas of what
[9:28] I should do with it? Now, fortunately,
[9:30] Julian saw the email, got in touch. And
[9:32] that's really how how, Cerrits came about.
[9:35] So we spent, you know, that, that was,
[9:37] well, I always started from 2016, but I
[9:40] think those guys have been working on it
[9:42] prior to, to that. But we've spent since
[9:44] about 2016, trying to develop Alan's technology into
[9:47] something which we could eventually use
[9:50] to re,
[9:52] reestablish this connection between the heart and lungs,
[9:54] restore RSA.
[9:56] And at the moment we're trying to identify
[10:00] whether,
[10:01] whether doing this has a therapeutic effect on
[10:03] patients with heart failure.
[10:05] Okay. I wanna bring in the ASH Lock
[10:07] here. You know, can you tell us a
[10:09] bit more about the technology and how that
[10:11] actually works?
[10:12] So as Stuart just touched on the respiratory
[10:15] sinus arrhythmia,
[10:17] how it is beneficial
[10:19] to the body, and
[10:21] you
[10:22] find that in healthy,
[10:23] humans.
[10:24] But in heart failure, that respiratory sinus arrhythmia
[10:28] doesn't exist.
[10:31] And another aspect of,
[10:33] respiratory sinus arrhythmia is that, heart rate variability,
[10:37] which is a good sign, again, present in
[10:40] healthy humans.
[10:41] So that heart rate variability is lost in
[10:44] heart failure in patients.
[10:46] So our technology, what it does is it
[10:48] mimics
[10:49] neural networks
[10:51] in the body,
[10:52] called central pattern generators,
[10:54] and these neural networks have specific tasks. They
[10:57] can generate rhythms
[10:59] without rhythmic inputs.
[11:01] And so, our electronics basically emulates
[11:04] those neural networks,
[11:06] and it generates rhythms,
[11:08] in coordination with restoration,
[11:11] and
[11:12] other,
[11:13] inputs.
[11:15] And it does it breath by breath
[11:17] Okay. To provide those subtle,
[11:20] respiratory sinus arrhythmia.
[11:23] And we we re so this way, we
[11:25] reinstate
[11:26] the healthy respiratory sinusoid pneumonia in the heart
[11:29] failure patients.
[11:32] And
[11:33] the,
[11:35] physiological
[11:36] improvements
[11:37] found was the increase in cardiac output by
[11:40] about 18 to 20%
[11:43] in the heart failure.
[11:45] Just to give a reference, 3% is considered
[11:48] significant.
[11:49] So, yeah, if you if you could put
[11:50] this in a pill form, it would be
[11:51] flying off the shelves and selling out. Yeah.
[11:54] So what does it actually look like in
[11:57] a patient? I mean, I guess you've you've
[11:58] done some animal studies so far?
[12:01] Yes. So the studies have been done in
[12:04] small animals and large animal models.
[12:07] And in both cases, we had similar amount
[12:09] of
[12:10] increase in the cardiac output.
[12:12] And,
[12:13] so in the the initial
[12:16] prototypes of the technology were just the electronic
[12:19] circuit on board and
[12:20] the trialed,
[12:22] in in the labs. But for the large
[12:24] animal trials,
[12:26] these were,
[12:28] again, in the static conditions in the lab.
[12:31] So
[12:32] what we're now trying to do is make
[12:34] them,
[12:37] we've got an external,
[12:39] pacemaker now. So and then the next stage
[12:42] is to make implantable,
[12:44] pacemaker out of this. And
[12:47] the electronics remains the same, but it shrinks,
[12:50] of course, a bit. Okay? Yeah. So you
[12:52] you've got potentially something you would wear on
[12:55] the outside, and then the next step is
[12:57] to make it so you can actually implant
[12:59] it. Implant it. Yes. I see. Okay.
[13:02] And you told me a little bit, Stuart,
[13:04] about how the company got started. How did
[13:06] you get involved in it? Because you're you're
[13:08] not you're not one of the 2 sort
[13:10] of the physicists and the physiologist,
[13:12] or clinicians, founders.
[13:14] I had I had kind of an interesting
[13:16] job. I mean, I'm a I'm a scientist
[13:17] by background,
[13:19] but at the time I was working for
[13:22] a company, it was essentially a a venture
[13:24] capital investment company.
[13:26] Now their USP
[13:28] at the time was that they had relationships
[13:30] with universities
[13:32] and they signed contracts with these universities, which
[13:34] would allow them to go in and meet
[13:36] the academics,
[13:37] look at the, research that they were doing,
[13:39] look at the IP that they were producing,
[13:41] and then they'd have kind of first dibs
[13:43] on potentially investing in that technology
[13:45] and, and, and, and spinning it out, essentially.
[13:48] So my role was to, I was the
[13:50] guy that went into the, into the university.
[13:52] So part of my patch within the, within
[13:54] the UK at the time
[13:56] to the Southwest and some of the London
[13:58] universities. So I'd go in all these universities,
[14:00] meet everyone and anything like the look of,
[14:03] I'd take it back to IP group at
[14:05] the time and,
[14:07] you know,
[14:08] pitched that we should, we should be backing
[14:10] this technology.
[14:12] So when I saw, when I saw this
[14:13] technology in 2016, I, I, it was, I
[14:16] mean, it was, I mean, I say this
[14:18] now, but I mean, it was the best
[14:19] thing I I'd seen with the universities. I
[14:21] mean, this is
[14:23] the the RSA,
[14:25] as a therapy for heart failure in itself
[14:27] is is massively exciting. You know, this is
[14:29] it is one of the big healthcare challenges.
[14:32] The expenditure on it on the heart failure
[14:34] is is, you know, it's only comparable by
[14:37] with cancer, to be honest, at the amount
[14:39] it costs that the health systems at the
[14:41] moment.
[14:42] And it's
[14:44] as with any disease, I suppose, you know,
[14:45] the world's getting older, the oil's getting fatter,
[14:49] and the problem's only getting worse. So that
[14:51] in itself is a is a is a
[14:52] big target. But the technology underneath is interesting.
[14:55] I mean, I'm not a physicist by background
[14:57] and I admit that, you know, I still
[14:59] struggle with with some of that
[15:02] with some of the theory behind how our
[15:04] devices
[15:05] our devices work, I could comprehend enough to
[15:08] see that this actually had the potential to
[15:10] be
[15:11] really a new approach to medical devices more
[15:13] more generally. I mean, I think as Ashok
[15:15] was saying and I was mentioning earlier, I
[15:17] mean, it it really does look at biology.
[15:19] How does, how is biology able to control
[15:22] the complex processes that go on within, within
[15:24] the system?
[15:26] Within the, within the body.
[15:29] And medical devices up to this point, we've
[15:31] kind of taken you know, electronic technology. So
[15:33] the same technology in your phones or your
[15:35] computers.
[15:36] And we kind of impose that on, on
[15:38] the body. And the 2 things don't communicate
[15:40] very well. One's
[15:42] a basic level. One's a digital system,
[15:45] communicating ones and zeros.
[15:47] One is a very complex analog system. So
[15:50] everything's, everything's 1, no everything
[15:53] in between.
[15:54] And the, and the body, that's how the
[15:56] body functions and trying to control that process
[15:58] of trying to correct biological processes using digital
[16:01] system in some ways, doesn't really make sense.
[16:05] So when you first saw what Alan and
[16:07] Julian were doing, you go, well, actually that
[16:09] makes sense. That's a sort of seamless connection
[16:11] between the human body. You can feed,
[16:14] biological signals into this technology and it can
[16:17] process it as part of its natural, natural
[16:19] functions. Whereas, you know, digital systems, you've got
[16:21] to take the, take the biological signal, you've
[16:23] got to filter it, you've got to process
[16:25] it to enable it to,
[16:27] to maybe to feed it into the, into
[16:29] the medical device itself. And what that means
[16:31] is you get very crude, you get very
[16:33] crude systems. I mean, most medical devices at
[16:36] the moment, a bit harsh,
[16:40] they just
[16:41] electrocute.
[16:42] They just electrocute in every of the body.
[16:44] I mean, the pacemaker today, you just get
[16:46] 60 electrocute
[16:47] the heart 60 times a second, 60 times
[16:49] a minute rather to control rate. You know,
[16:52] Parkinson's disease brain implants, it's mostly just as
[16:55] simple
[16:56] stimulation in particular area of the brain. There's
[16:58] not a lot of complexity there. There's not
[16:59] a lot of feedback.
[17:01] So I thought that, you know, this first
[17:03] application in heart failure is incredibly exciting, but
[17:05] there's more to it there. I think that,
[17:07] you know, further down the line,
[17:09] certainly Ceryx's more biomimetic approach, create
[17:12] mimic the systems that they're trying to to
[17:15] control, makes makes a lot of sense.
[17:18] And that's kind of the premise that that
[17:19] it came from. So I, yeah, getting back
[17:21] to your question, I mean, I, I, you
[17:23] know, I found the technology in 2016. I
[17:25] continued to work for IP Group. We, we
[17:27] did some early investments into, into CEREC after
[17:29] we spun out of, of Bath and Bristol
[17:31] Universities.
[17:33] And then in 2019,
[17:36] say IP group, you decided to take a
[17:38] different route. It's got moved away from the
[17:40] university model. They didn't want to, they couldn't,
[17:43] can we work with the universities in the
[17:45] same way they had before? So when they
[17:47] went off in that direction, not I stayed
[17:49] behind, and I left IP group and and
[17:51] joined CEREC full time.
[17:54] Yeah. That's how I came about.
[17:56] And, Ashlag, you you are a physicist by
[17:58] background. How did you get interested in this
[18:00] this technology and and get involved in helping
[18:03] to make it it work? So
[18:05] I was a doctoral student of professor Nagar
[18:08] in University of Bath. And, when I was
[18:11] finishing my PhD, there was
[18:13] a this project had,
[18:15] was going on. And so there
[18:18] was
[18:20] a position for postdoctoral
[18:21] researcher in in that group,
[18:24] on that project. So
[18:25] I found it fascinating. So I joined the
[18:27] project, and I spent few years
[18:30] developing actually the
[18:32] hardware and
[18:33] the technology and working between the labs labs
[18:36] of professor Norbert and professor Julian.
[18:39] And what was the most difficult part of
[18:41] that task instead of developing the technology?
[18:46] As there are 2 different disciplines involved, there
[18:49] are challenges from both disciplines. 1st was,
[18:53] actually making the
[18:54] hardware designs and studying the dynamics that will
[18:58] be,
[18:59] dynamics of the network that will be more
[19:01] useful in coordinating respiration and heartbeat.
[19:05] And then
[19:07] bring bringing it, for physiological application and actually
[19:11] saying,
[19:12] for example, tuning the parameters
[19:15] and the range and the rate of adaptation,
[19:17] those kind
[19:18] of technical details that you have to work
[19:20] out from the scratch in in a different
[19:23] lab, which is physiology lab. And I wasn't
[19:28] a a physiologist from background. So it was
[19:30] a learning process
[19:32] on 2 different levels,
[19:34] but, eventually, we got there.
[19:36] And, Stuart, what will you say in terms
[19:37] of what was the most difficult challenge you
[19:39] had from the business side of things to
[19:41] get this this company to where it where
[19:43] it is now?
[19:46] I'm not sure. I put I should put
[19:47] this out in a in a podcast, but,
[19:49] I mean, the the biggest problem for any
[19:50] any start up is always funding.
[19:53] It's so
[19:55] so much effort is put into just, just
[19:58] feeding
[19:59] cash into,
[20:01] into, into the business. I mean, we're, we
[20:04] Ceryx has been quite,
[20:06] efficient, I think in the way that he's
[20:08] done things. You know, we've got a very,
[20:09] we've got a small but highly
[20:12] experienced
[20:13] team.
[20:14] We've also been quite smart in how we've
[20:15] been using sort of external subcontractors just to
[20:18] kind of keep sort of overheads overheads down
[20:21] and proceed as, as efficiently as possible.
[20:24] So our cash requirements have been kept to
[20:26] a minimum, but it's but it's just been
[20:28] so difficult to to raise the to raise
[20:30] the money. I mean, one of the things
[20:32] that you want to do
[20:34] with any
[20:35] development program is is to keep momentum. You've
[20:38] got to keep pace up.
[20:42] And sometimes
[20:43] doing that alongside
[20:45] funding timescales
[20:46] is just really, really hard. I mean, on
[20:48] the one hand you have, you have grants.
[20:50] Sometimes they have like ludicrous
[20:53] process which can take, you know, 12 months
[20:55] or so.
[20:57] And, you know, that just doesn't fit with
[20:59] a fast moving,
[21:00] startup. You know, we've, we've 12 months' time,
[21:03] we'll have we're
[21:05] in a completely different place than where we
[21:07] were 12 months ago. Trying to plan that
[21:08] ahead is quite difficult.
[21:11] Investment
[21:11] in the account I mean, I think that
[21:13] we, you know, we were unlucky, I think,
[21:15] in that, you know, when we really started
[21:17] to move around sort of 2018, 2019, we
[21:19] started getting into the sort of pandemic type
[21:21] period
[21:22] and then everything became a lot more difficult.
[21:25] Funding became a lot more difficult. I mean,
[21:27] even now,
[21:28] you know, investors tell me that they're having
[21:30] difficulty raising money. So us raising money from
[21:32] then, everything was quite difficult.
[21:34] I mean, we were
[21:36] we did well. We wrote we closed a
[21:38] pretty large round,
[21:40] nearly nearly 3 years ago now where we
[21:42] we wrote oversubscribed.
[21:46] But even then, it was, you know, it
[21:47] was it was a 14 month process, I
[21:49] think, to to to.
[21:53] I do think as well that, you know,
[21:55] working in the space where, that we are,
[21:58] I mean, investors have a, to be fair,
[22:00] I mean, I've been one, so I know
[22:01] that investors have a hard time with it.
[22:02] They, they look at a lot of technologies,
[22:04] a lot of companies, there's a lot of
[22:06] information that they take in. And very often,
[22:08] you know, they, they they're dealing with the
[22:10] business side and they come from a financial
[22:12] background.
[22:14] And I'll sit them down in front of
[22:15] a physicist and just go, come on, why
[22:17] don't you appreciate how brilliant this is? And
[22:19] it's really hard for them to do that.
[22:20] But I mean, it is particularly hard, I
[22:22] think for CEREX because we, as Ashok said,
[22:24] we encompass so many different aspects. We've got,
[22:27] you know, cardiovascular physiology,
[22:29] we've got electronics, we've got physics, we've got
[22:32] mathematics.
[22:34] And
[22:35] part of the beauty of what we do
[22:36] is in the complexity
[22:37] of the technology.
[22:39] It's why, you know, it's why we've been
[22:40] able to achieve
[22:42] what we have with RSA with other other
[22:44] people may not have been able to because
[22:45] it is, it is quite complex and that's
[22:47] what's great about it. But trying to communicate
[22:50] that message in a way that people just
[22:52] don't
[22:53] investors in particular, don't just turn off and
[22:55] just go, no, actually this one's too hard.
[22:57] I'll look at the next, I'll look at
[22:58] the next technology. At least I slightly understand
[23:00] it
[23:01] is, is a difficult problem. I mean, and
[23:04] yeah, so
[23:06] that's my long winded answer to say, yeah,
[23:08] just, just, just cash. But I think any,
[23:10] any startup probably in the world will say
[23:12] exactly the same thing. Just, just sourcing funding
[23:15] for, for even, it doesn't matter how brilliant
[23:17] your idea is.
[23:19] Getting getting cash to fund it is always
[23:21] the challenge.
[23:23] And I understand you're you're about to enter,
[23:25] a new and and differently challenging phase for
[23:28] the company. You're you're starting your first in
[23:29] human trials. What sort of challenges does that
[23:32] bring? Maybe, Ashlag, you wanna go first?
[23:35] So
[23:36] some of that are the regulatory
[23:38] approval we need. It takes a very long
[23:41] time and longer
[23:43] document preparation.
[23:45] And
[23:45] even before that is the preparation for the
[23:47] technology
[23:49] that will be evaluated
[23:50] for
[23:51] regulatory approval.
[23:53] So we
[23:54] again, then we have to coordinate,
[23:56] as Sushu said, electronics, physics,
[23:59] and mathematics, and everything.
[24:01] And we have to commit to a design
[24:03] of the technology.
[24:05] There can be other versions, improved versions later
[24:07] on, but we have to then commit to
[24:09] a certain design before
[24:11] we file for the regulatory approval. So
[24:13] that was a challenging part from my side,
[24:16] and I think Stew can add further.
[24:19] So from from the clinical side, I mean,
[24:21] we as I said, we've we've been pretty
[24:23] efficient, I think, in the development. We went
[24:25] from a we went pretty much from a
[24:26] standing start to
[24:28] a,
[24:30] an MHRA approved class c medical device in
[24:32] about 2 years, which is pretty good going.
[24:35] And then we thought, right, we just gotta
[24:37] just gotta put it on a patient now.
[24:38] It's all been approved.
[24:41] And, it actually is been incredibly incredibly challenging.
[24:44] I mean, obviously, you know, the patients we're
[24:46] dealing with are really quite really quite sick.
[24:48] I mean, heart failure is a serious condition.
[24:50] For this clinical study, we're taking patients who
[24:53] have got heart failure, who are going in
[24:55] for a coronary artery bypass
[24:57] graft operation. Now why we were interested in
[24:59] these patients is because
[25:01] these patients as part of standard clinical care
[25:03] are fitted with an external pacing device. So
[25:06] when they go in, they go in for
[25:07] the procedure and just when the surgeons finish,
[25:09] you'll put a couple of pacing wires, 1
[25:11] in the atrium, 1 in the ventricle.
[25:13] And these wires then just come out through
[25:15] a through a hole in the chest
[25:17] and a patient is stitched up. And when
[25:18] they get taken down to the ICU, they'll
[25:20] they'll have a an external pacing box. And
[25:23] that just controls their heart rhythm as a
[25:26] surgeon who recovered from the anesthesia. They can
[25:28] be at sort of high risk for arrhythmias
[25:29] there, so that prevents that from happening.
[25:31] But generally what will happen the next day
[25:33] is the cardiologist's surgeon will come round.
[25:35] They'll turn down the pacing on this device.
[25:37] And if that patient's got a normal sinus
[25:39] rhythm,
[25:40] they'll turn that pacing box off. Generally, the
[25:42] wires stay in for a couple more days
[25:44] just in case the pacing's needed. But eventually,
[25:46] the nurses will just come around and they'll
[25:48] just basically just tug on the wires and
[25:49] it they come off the outside of the
[25:51] heart and they'll stitch them up and away
[25:52] they go. So we were interested there because
[25:55] that's an opportunity for us to
[25:57] where pacing is huge without having to implant
[26:00] the device into the patients. What we've done
[26:02] for this first study is taken our technology
[26:04] and integrated it with an existing external pacing
[26:07] device. So they can be fitted with that
[26:09] pacemaker when they come out surgery
[26:11] and just give a normal pacing. And then
[26:12] when they're ready to come off that pacemaker,
[26:14] we switch it over and then it gives
[26:15] them their
[26:16] delivers RSA pacing. And we'll just leave that
[26:19] on for the duration that patient remains in
[26:21] hospital, which is, you know, typically about sort
[26:23] of 5 days or so. So I'll give
[26:25] this first indication of the kind of safety
[26:28] and feasibility of RSA patient in patients. But
[26:30] maybe also we'll get some early indications of
[26:32] efficacy.
[26:33] You know, we're that's what we're hoping. But
[26:35] lot there's a lot going on there. I
[26:37] mean, these patients, as I say, these patients
[26:38] got heart failure. They were going in for
[26:40] a coronary artery bypass. There are risks to
[26:42] that, to that, to that operation.
[26:45] So, you know, getting that ulcer approval as
[26:47] Assoc Sheikin said is quite challenging, but then
[26:49] also getting the patients into the study are
[26:51] quite difficult.
[26:52] One problem that we didn't expect that we've
[26:55] found in these early weeks of the study
[26:57] is that
[26:58] often
[26:59] these patients are being admitted to hospital several
[27:01] weeks before they have their surgery.
[27:04] Now sometimes they've kind of got themselves in
[27:06] a bad way because maybe they haven't been
[27:07] able to manage their diseases as well as
[27:10] they, as well as they might.
[27:12] One of our first candidates had quite severe
[27:14] diabetes
[27:15] and hadn't been very good at managing that
[27:17] diabetes. So of course, when they came into
[27:19] the hospital,
[27:20] the nurses were all over them. They they
[27:22] optimized their their their therapy. They monitored their
[27:24] diabetes properly. And what we found was that
[27:26] this patient was quite unwell when they came
[27:28] into hospital. By the time they came out
[27:30] and had the surgery, they were actually too
[27:31] healthy to be included in our study. So
[27:34] it's great for them, but, yeah.
[27:36] And actually that's happened quite a few times
[27:38] now. So it was this problem of the
[27:40] it was basically the hospital was doing the
[27:42] job too well. They were we're, like, making
[27:43] these patients well
[27:45] for us.
[27:46] And then, you know, occasionally you get complications
[27:48] from the surgery, you know,
[27:50] one guy unfortunately got a bit of a
[27:52] bleed after the surgery, had to be readmitted.
[27:54] I mean, he was fine after the surgeons
[27:55] had another go, but, but, you know, it
[27:58] excluded him from the study. So it's
[28:00] it's it's a it's an interesting but frustrating
[28:03] period. You know, as scientists, we used to
[28:05] set up our experiment and then we do
[28:07] the experiment. Here we've got, you know, health
[28:09] systems and patients
[28:11] and medicine getting in the way and it's,
[28:13] it's, it's,
[28:14] yeah. It's
[28:16] making me call my hair out at the
[28:17] moment, but we're getting there.
[28:19] How long has this clinical trial's meant to
[28:21] last, and then what happens after that?
[28:24] So we're gonna we're gonna look for a
[28:25] sort of a we're looking sort of 12,
[28:27] 18 month recruitment period. We've we've actually gone
[28:30] quite large with, with this study.
[28:33] So normally as a sort of first in
[28:34] human evaluation, we go for about sort of
[28:36] 15 patients.
[28:38] Based on the data we saw from the
[28:39] preclinical work, we've kind of pushed it to
[28:42] 30 patients
[28:43] because we sort of
[28:45] based on the human animal data, maybe if
[28:47] we recruited that many patients, we might start
[28:49] to see some, some significant
[28:50] indications of efficacy in these, in these patients.
[28:54] Now there's 2 ways that this could go
[28:56] after, after this study.
[28:58] We've, we've sort of, you know, this is
[28:59] a first in humans, so we just want
[29:01] to show that RSA pacing is safe and
[29:03] that provides us as a gateway to then
[29:05] take the next step, miniaturize our technology
[29:07] and implant it with patients with more straightforward
[29:10] heart failure,
[29:11] and then pace them over a longer period
[29:13] of time. That gives us a much that
[29:14] gives us, you know, months of therapy rather
[29:17] than the days of therapy that we're getting
[29:19] this study.
[29:20] And then we should get an indication of
[29:21] the full effect of of RSA therapy.
[29:25] However,
[29:26] there is the possibility. I mean, all patients
[29:28] that go in for, for, for heart surgery
[29:30] generally have depressed cardiac function when they come
[29:33] out. The heart's been, you know, your chest
[29:34] has been open. The heart's been messed around
[29:36] with its, you know, it doesn't like. It.
[29:38] So your cardiac output probably is going to
[29:39] be down for a few days to, you
[29:41] know, few days to a few weeks post
[29:43] surgery.
[29:44] Now with most patients, it slowly recovers and
[29:46] the patients will feel better as that, as
[29:48] that comes around.
[29:49] But there are patients about 15% of patients
[29:52] where that, that recovery never really happens. And
[29:54] there'll have to be additional interventions to try
[29:56] and,
[29:57] make up for this, this deficit in cardiac
[30:00] function.
[30:01] So if we had a device whereby, you
[30:03] know, these patients are getting pacemakers anyway, if
[30:05] you fitted them with an RSA pacemaker, we'd
[30:07] not only protect them against those arrhythmias,
[30:09] but would also improve their cardiac function.
[30:12] Would that mean that those 15% of patients
[30:14] never, you know, get that prolonged depressed,
[30:17] cardiac function. And also all patients, the quicker
[30:21] you can improve their cardiac function, the quicker
[30:23] they're going to recover and the better they're
[30:24] going to feel. So maybe it would be
[30:26] a solution for all patients having, having reduced
[30:28] cardiac,
[30:29] having cardiac surgery.
[30:31] So there is there is kind of 2
[30:33] possibilities for this study. 1, you know, it's
[30:35] just the, you know, the first stepping stone
[30:37] in our development for long term therapy for
[30:39] heart failure, but also potentially it's a new
[30:41] therapy for all patients going in for cardiac
[30:43] surgery.
[30:44] And we'll just have to,
[30:46] just wait and see. Now I understand that
[30:50] that, you know, this is you're looking at
[30:52] at cardiac
[30:53] applications of this sort of,
[30:55] you know,
[30:57] your the core technology in the first place.
[30:59] Are there any other areas where this, you
[31:02] know, sort of I guess you could see
[31:04] appreciation of of the nonlinear nature of the
[31:07] body signals could and and coupling an external
[31:11] or implanted
[31:12] electrical device to that. Are there other applications
[31:15] where that could also
[31:16] be effective clinically?
[31:19] Yeah. So, I mean, if if you know,
[31:21] just to throw a few examples out there.
[31:22] I mean, you know, you said, you know,
[31:24] the body's full of nonlinearity,
[31:26] and we think our technology will be ideally
[31:28] suited
[31:29] to a more physiological control to these mechanisms.
[31:32] So one area that Ashford's been looking at
[31:34] is,
[31:35] a condition called dysphagia,
[31:37] which where you ability to swallow. And this
[31:40] most commonly occurs after people have had a
[31:42] had a stroke.
[31:43] Now swallowing is is a coordination of about
[31:46] a dozen muscles within the within the throat,
[31:48] And they all have to have, they all
[31:50] have a rhythmical contraction, which needs to be
[31:52] coordinated.
[31:54] There are medical device therapies out there for
[31:56] dysphasia,
[31:57] but they tend to be, you know, a
[31:59] single point, electrical stimulation
[32:01] of the throat or they are special foods
[32:04] that makes it easier for the for the
[32:06] patient to to swallow.
[32:08] Whereas our technology, we're really good at taking
[32:10] input from those 12 muscles, which were currently
[32:13] dysfunctional and then coordinate
[32:15] their contraction into the appropriate rhythm to to
[32:18] enable swallowing.
[32:22] There obviously
[32:23] are the
[32:24] your di rest of your digestive tract also
[32:27] is coordinate is a coordination of multiple muscle,
[32:29] give that peristaltic motion. And there are certainly
[32:32] plenty of patients out there that have,
[32:35] problems
[32:35] with the, lower digestive tract.
[32:39] The
[32:39] example that I started with of your legs
[32:42] is, I suppose, is the most obvious one.
[32:44] And that's really the kind of
[32:47] ultimate
[32:48] application for our technology.
[32:49] I mean,
[32:51] Ashok talked about central pattern. Right? Is those
[32:54] those networks of of neurons in your in
[32:57] your spine are are amongst the most complicated
[32:59] ones that we thought we might we might
[33:01] tackle. But,
[33:03] I'm a little cat story. I had, people
[33:06] have told me to stop telling the cat
[33:07] story, but it's a bit off tangent. But
[33:09] basically if you go, if you go on
[33:11] YouTube, there is, and you can find it,
[33:12] there's a black, grainy black and white image,
[33:15] video really.
[33:17] And I imagine it's black and white because
[33:19] you probably can't do these experiments anymore, but
[33:22] what they've done to it, they've taken it
[33:23] out and they've decerebralized the cat. So basically
[33:25] severed the connection between the cat's brain and
[33:28] the cat's legs. So you would assume this
[33:30] cat to be paralyzed, but what they do
[33:31] is they take the cat and they put
[33:32] it onto a treadmill. And as soon as
[33:34] the cat's feet touch the treadmill, it starts
[33:37] to start to walk and they'll turn the
[33:39] treadmill up and the cat will start to
[33:40] run. And they, for some reason, they put
[33:42] a little trolley on the back of it
[33:43] and they pull the car. I don't know
[33:45] the necessity of doing that, but it just
[33:47] shows that it can change the gait, I
[33:49] suppose, of, of the animal, even though there's
[33:52] no connection there between the brain and the,
[33:53] and the, and the legs. Now I'd always
[33:55] assume that your brain had something to do
[33:56] with your ability to walk, but it seems
[33:58] that you just like where you want to
[34:00] go and then your legs kind
[34:02] of control themselves. And the way they do
[34:04] that is they send sensory inputs up to
[34:06] the spine, the central pattern generators process that
[34:09] information, then send the,
[34:11] the stimulator impulses down to your legs. And
[34:14] that provides the coordination of the muscles, which
[34:17] allows us, which allows us to walk. And
[34:19] that experiment that they performed, which is demonstrating
[34:22] that the
[34:23] legs is mediated by
[34:26] the nerves within the spine, rather than also
[34:28] the brain. So for us, that means that
[34:30] someone who's had a,
[34:31] a spinal cord injury, maybe it's even severed
[34:33] to the spinal cord, we could set we
[34:35] could rep
[34:37] those central pattern generators in the spine and
[34:38] restore the ability to to walk.
[34:41] Like Stuart explained,
[34:43] so these are central pattern generators that control
[34:45] the rhythms and then stimulate the muscles, and
[34:47] that generates different gait for the legs. And
[34:51] if there's somebody's amputated,
[34:53] and
[34:54] they can be used to control those artificial
[34:57] legs.
[34:58] But the control of arms is even more
[35:00] complex where you have
[35:02] different,
[35:03] fingers and
[35:04] different grip sizes. So this nonlinear
[35:08] dynamics of the central pattern generators
[35:10] can then be used to
[35:12] control the movement of arms
[35:15] with different crypt levels. If you imagine the
[35:17] complexity of the network, it can be extended
[35:20] by adding more neurons to it.
[35:22] And this would presumably require quite a lot
[35:24] of computational power as well.
[35:26] It would. And if it's to be done
[35:28] digitally,
[35:29] but in analog systems,
[35:32] it can be done much more efficiently,
[35:35] because it'll be real time,
[35:37] as it's a nonlinear and continuous time
[35:41] signals generation.
[35:42] So the
[35:45] and lots of parameters are already
[35:47] defined
[35:48] so that you, ma'am, you'd you won't have
[35:50] to look for the
[35:52] certain level of inputs and then make decisions.
[35:55] It will be much more dynamic than that.
[35:58] So that's where the true power of the
[36:00] continuous systems,
[36:02] will be in nonlinear systems, will it?
[36:05] Well
[36:06] and
[36:07] so final question for for both of you,
[36:09] actually. You know,
[36:10] what do you know now
[36:12] that you wish you knew when you started
[36:14] this journey back in 2016, in your case,
[36:17] Stuart, and when you're starting on your your
[36:19] postdoc Ashok?
[36:21] I mean, it's certainly the I mean, there
[36:22] are some of the boring ones and you
[36:24] can fill them out. So, I mean, I
[36:25] think the I think the clinic I think
[36:26] the clinical side of things has been a
[36:28] bit little bit of surprise. I mean, I
[36:29] think that when we when we when we
[36:30] can we thought the message the biggest challenge
[36:32] was gonna be the regulatory approval for the
[36:34] device, but we were actually
[36:38] pretty pleased with the way with the speed
[36:40] with which, you know, the the authorities processed,
[36:44] and evaluated our technology. And that was really
[36:46] straightforward.
[36:48] Getting into the clinic, I was warned, I
[36:50] think, that it would take 6 months from
[36:52] that point to, to getting the first patient
[36:54] in, and I didn't believe them.
[36:56] And they were right. And they were right.
[36:58] And,
[36:59] yeah. And I, I didn't appreciate that the
[37:01] just what is involved with what seemed to
[37:03] be a relatively straightforward
[37:05] straight.
[37:07] In terms of starting out the
[37:11] I think that it took us a little
[37:12] bit of time.
[37:14] I mean, the the thing about our technology
[37:16] is that the
[37:17] the clever bit is the is the, you
[37:19] know, this this
[37:20] this this core
[37:21] technology, I say, that's actually
[37:24] the the tech. The rest of the device,
[37:26] you know, we talked about this the the
[37:27] clinical study being involving an external pacing system
[37:30] that we've modified with our technology.
[37:32] So 99%
[37:33] of the device is is just a standard
[37:35] pacemaker and the implantable will be exactly the
[37:38] same. It's just a pacemaker with our with
[37:39] our chip
[37:40] in place. So I think we started with
[37:42] the premise that, you know, let's let's go
[37:45] and talk to Medtronic or one of the
[37:47] other big corporates.
[37:48] They'll give us their pacemaker. We'll put our
[37:50] chip in it. And there we go. That's,
[37:51] that's, that's, that's kind of done. And there
[37:54] were 2 things that we've learned over the
[37:55] years. 1, they're not prepared to do that.
[37:58] And 2, we don't need them to do
[38:00] that actually because because this technology has been
[38:03] around since the fifties,
[38:05] most of the most of what's
[38:07] required is there
[38:09] is available from particular support. The technology and
[38:12] the challenge of putting them together is not,
[38:14] is not that great. So I think we're
[38:16] much more self sufficient now than we were,
[38:19] you know, 3 or 4 years ago.
[38:22] When we
[38:23] in terms of the route that we're choosing
[38:25] to develop this technology, it's like, you know,
[38:27] no one's gonna help you do this. You
[38:29] just gotta do it yourself, but actually, doing
[38:31] it yourself is probably the most efficient way
[38:33] to do it anyway. So
[38:35] Ashok, do you have anything to add to
[38:36] that?
[38:37] I I would add from my point of
[38:39] view, I think
[38:41] transition from academia to industry
[38:44] has been a big learning,
[38:46] although you hear lots of
[38:50] suggestions,
[38:50] they're all valid, but experiencing them and
[38:55] actually, dealing with them is a slightly different
[38:58] story. But,
[38:59] especially with the start ups, things are very
[39:02] dynamic.
[39:03] And the key difference between academia and industry
[39:06] is the pace at which you can do
[39:08] the things. Of course, a lot of academic
[39:11] work has been done. And when
[39:13] you're making a product, even if it is
[39:15] that level of complexity going into human body,
[39:21] you can do things much faster than
[39:24] in academia. And
[39:26] so you need to be
[39:28] mentally prepared for that dynamism in the startups.
[39:31] And,
[39:33] the other is the communication.
[39:36] So
[39:38] especially in our case, because there have been
[39:40] multiple disciplines involved.
[39:42] And
[39:43] as Stuart mentioned, investors who are not from
[39:46] science background or physics background, to convince them.
[39:49] So you need to
[39:50] speak at multiple levels,
[39:52] of complexity
[39:54] and
[39:55] the details. Oh, and
[39:58] it's a learning process. I'm still learning, and
[40:01] then but I think I've come a long
[40:02] way.
[40:03] There's a long way to go as well.
[40:06] Well, thank you both for for, coming and
[40:08] and and talking to me today. I really
[40:09] appreciate it. Stuart Naschach, thank you very much
[40:11] for joining us in the Physicworld podcast.
[40:14] Brilliant. Thank you very much.
[40:23] I'm afraid that's all the time we have
[40:25] for this week's podcast.
[40:27] Thanks to CRX Medical's
[40:29] Stuart Plant
[40:30] and Ashok Chowan
[40:32] for a fascinating discussion,
[40:34] And also thanks to Margaret Harris for asking
[40:37] the questions,
[40:38] and to Fred Iles for producing the audio
[40:42] in this podcast.
[40:43] We'll be back again next week.

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