Many of us have a proclivity to putting humans on a pedestal. Our species’ accomplishments are awe-inspiring and are testaments to just how special we are. Nevertheless, evolution will continue to select for humans that are even better adapted to the environment than we are, so we have not reached some developmental pinnacle.
This said, human biology is in many ways marvelous. In early embryonic development, for instance, human eggs can reverse degenerative processes, ensuring that newborns enter the world as unblemished as they are. After birth, some of our cells are rapidly turned over (such as blood, gut, and skin cells), and several of our organs have impressive regenerative capacities, one example of which is the liver.
However, our biology has been programmed for procreation rather than longevity, and as we age our bodies inexorably deteriorate. Joints ache, skin wrinkles, memories fade, and once-healthy cells can mutate into life-threatening tumors. I discussed some of the underlying reasons with Dr. Aubrey de Grey in a previous episode of humanOS Radio.
Many other organisms have superhuman abilities, such as the capacity to ward off cancer, periodically reverse aging, regenerate limbs (“epimorphic regeneration”), and even regrow brains. Yet these non-human species share many genetic similarities with us. This naturally raises the question of whether we can learn from other animals in our quest to delay aging, reverse disease, and – dare I say it – return to life from the empty expanse of death. These lofty goals bring us to the latest episode of humanOS radio.
In this episode, I speak with Ira Pastor, CEO of Bioquark, a life sciences company that focuses on how to induce bodily regeneration, repair, and rejuvenation, by using pharmaceuticals that support our bodies’ in-built restorative processes. Ira has more than 30 years of experience working in the pharmaceutical industry, and this background has helped shape the visionary path that Bioquark has embarked upon.
At present, most pharmaceutical companies focus on treating disease by developing single-compound drugs with narrow a narrow range of effects. Occasionally this makes sense, for even if disease is generally due to widespread dysfunction in many bodily systems, sometimes a single organ is mostly at fault, as in the case of heart attack (myocardial infarction). In these cases, organ transplantation can be lifesaving, but there is a finite number of organ donors, and transplantation risks rejection of the new organ by the recipient’s body. Such problems with traditional methods have spawned novel strategies for targeting biological dysfunction, an example of which is stem cell therapies. So far, however, substantial technical barriers have arisen in this line of research.
To address limitations of other approaches, Bioquark is developing “combinatorial biologics” (“bioquantines”). Biologics are drug treatments that have been extracted from or manufactured in living systems. An example of a biologic is growth hormone. Combinatorial biologics are biologics that have many effects concurrently. Combinatorial biologics may be used preemptively to postpone dysfunction. Alternatively, they can be designed to treat disease. A key premise of this approach is that combinatorial biologics can be used to zero in on the changing events that lead healthy tissues to become problematic. Rather than focusing on targeting cancerous tumor cells for destruction, for example, combinatorial biologics may be used to reverse the epigenetic processes that propagate dysfunction. And as Ira points out, the causative events in disease often share commonalities:
“When you put that 7 trillion dollars that we spend around the world nowadays on healthcare (when you cut out infectious diseases), the majority of all that money is spent on either diseases that have an underlying cellular degeneration component… or have an underlying cellular damage component.”
If you consider the vast number of small chemical entities present in biological systems though, the task of identifying combinatorial biologics might seem insurmountable.
So, how is Bioquark identifying combinatorial biologics?
What have they studied so far, and what has this work shown?
And what do Ira and his team hope to address in years to come?
Tune in below to find out more!
Dan prepared for and conducted the interview, Greg wrote the first draft of this blog post, Dan edited the draft, and Ira continues to do the hard work!
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Ira Pastor - 00:06: There's a lot of thought leaders out there that are saying we really need a different approach with oncology, is thinking about the changing events, not the kill event which is secondary, but how we alter the epigenetics of that tumor in a broader sense to turn it back into a tissue that originally was or turn it back into the tissue where it now resides.
Kendall Kendrick - 00:29: HumanOS, learn, master, achieve.
Dan Pardi - 00:39: Ira Pastor, welcome to HumanOS Radio. Thank you for joining me. Tell us about yourself.
Ira Pastor - 00:44: I am a 30 plus year veteran of the traditional pharmaceutical industry that has spent time in various facets or another of this segment, from retail to Big Pharma to the small biotech. But at my heart, I'm still a kid that came up reading comic books and watching science fiction movies. Always being interested in how I could advance the human condition and realize some of the future that I only read about in fiction and saw on the pages of those comic books.
01:13: So, if you want to say how I got involved in sort of this cutting-edge area of regenerative medicine and biotech, it was really started at a very young age. Let's say I honed it and I learned quite a bit on the job the last 30 years, but a lot of it goes back to sort of just a childish enthusiasm for creating the future and what it could be.
Dan Pardi - 01:32: Tell us about your company, Bioquark.
Ira Pastor - 01:34: We are in life sciences company focused on how we can induce endogenous regeneration and pair and rejuvenation. So, the three R's of our complex organs and tissues. We spend a lot of time studying those organisms which inhabit this planet with us, which from a health and wellness perspective are just so further advanced than we are today. Whether that refers to the members of say the amphibian kingdom that can replace lost or damaged organs and tissues that are identical, instruction function throughout their lifetime, including spinal cords and limbs and large segments of hearts and brains. Or whether it is the cancer reversion skills of organisms like planarians, which get cancer but shrug it off as if it was the common cold and just turn tumors into normal healthy tissue. Or whether it's the far end of the spectrum.
02:33: There's organisms out there that do not age. There are those that like to age in reverse, and there's even a few that die and are reborn. Needless to say, we're very weak as humans when it comes to accomplishing these speeds, but we wanted to ... Basically, our mission is to change that and how we reawaken some of these capabilities in humans using the tools that have been developed the last hundred years in the biopharma space. Ultimately, we're a biologic biopharmaceutical company that is looking to create products, pharmaceuticals that can endogenously stimulate these capabilities for really important degenerative and imperative needs in unmet medical diseases.
Dan Pardi - 03:12: What's the philosophy about why humans haven't either maintained or developed the same regenerative capabilities as some of the examples that you've provided?
Ira Pastor - 03:21: Well, the main one, which a lot of the evolutionary biology people will talk about is the fact that in our transition through evolution around the time where we as mammals separated from reptiles, the way our circulatory system developed, we became very significant bleeders. We are a species that bleeds very rapidly, we die from the loss of blood very rapidly and our systems over time were biased for very strong thrombosis and fibrosis to keep that blood from getting out. Rapid wound healing is wonderful thing for us, but it is not a friend of the slow meticulous regeneration that we see in nature.
03:58: That being said, at the same time, we do maintain some regenerative capability. We have physiological turnover in all of our rapidly dividing cells, blood, epithelium layer of skin and gut. We do have some hypertrophic regeneration capabilities and our liver if we ever come across acute damage where we will not have proper structural regeneration, but the liver will increase in both cell count and size to take one missing function. And then most importantly, I like to point out that we do have some pretty decent reversion capabilities in our tissues.
04:33: The ability of, a good example, when cell A in our body somewhere starts going wrong and undertakes a oncogenic transformation, it's basically sell B, C, D, E, and F in the immediate micro environment that nudge it back into shape. That is a very rudimentary form of reversion, which we don't see on a huge scale in humans. But nonetheless, it is a sort of vestigial remnants of that process.
Dan Pardi - 04:58: So, you're looking to understand that the micro environment of tissues and how this regeneration could be intervened upon to fix things that are damaged in the body over the course of life.
Ira Pastor - 05:09: Exactly. We have great proxies for it in the sense that we have nature to look at. We have all of the non-human species that from a genetic perspective, although we all look kind of different we're pretty much genetically the same. So, we have a lot of things to work with. At the same time, we have just the examples in humans, such as an early embryonic development where they are existence this morphogenetic capability to replace what's missing and reverted disease state.
05:35: So, we have a lot of good information that evolution last couple billion years is put in front of us and we're going to derive that information and translate it into therapeutic opportunities for humans.
Dan Pardi - 05:46: These opportunities you described them as combinatorial biologics. I'd like to break that word down. Talk to us about biologics, what are those? And then this idea of combinatorial or combination, talk to us about the technology.
Ira Pastor - 05:58: Biologics or any drug treatment that are produced in living cell systems, are either protein, carbohydrate or protein and carbohydrate based, and do not have an exact composition of matter as a synthetic chemical might. Biologic examples are everything from growth hormones to interleukins, interferons, insulin and vaccines as well. When we put the word combinatorial before it, we are referring to in a particular case the interest to develop drug or therapeutic interventions that do more than one thing.
06:33: The pharmaceutical industry for the last hundred years has been very based on what is referred to in the industry as sort of the single silver magic bullet. They like developing single biologic moieties or biochemical moieties that do one thing, that is what they've been good at and it's what is easy for them to get approved. But at the end of the day, when you're talking about God forbid, your arm gets chopped off, growing an arm back is a very complex process. There is no single magic bullet that will ever for now until infinity ever do that. It is a combination of biochemical activities that gets that done for the newts or the lizard.
07:07: So, we are studying what these processes are and how we can put together combination interventions, as opposed to single magic bullets. We see some of this in the market today. You see combination therapies for of course cancer. You see it in the case of HIV, and then you see therapeutics, some of which are on the market for a long period of time, which are combinations. We don't really think of them, but they exist. It's really moving beyond the silver bullet thinking to more systems-based thinking on what a therapeutic may look like that does multiple things.
Dan Pardi - 07:40: Biologic is a form of a drug or intervention replicating what is found in the human body or in nature. combinatorial means that it's having more than one effect, but also it sounds like it can contain more than one substance in the formulation, is that true?
Ira Pastor - 07:53: Perfect.
Dan Pardi - 07:54: Talk to me about some of the applications that you feel combinatorial biologics can affect in the near term, and what are some of the potential moonshots just so we can get the scope of what we're looking at here in terms of what could be addressed?
Ira Pastor - 08:07: Sure. Absolutely. Just taking a step back to the big picture. When you put that $7 trillion that we spend around the world nowadays on health care. When you cut out infectious diseases, the majority of all that money is spent on either diseases that have an underlying cellular degeneration component. So, you think your Alzheimer's, congestive heart failure, Parkinson's, diabetes, so forth. Or, have an underlying cellular damage component. Fibrotic disorders, cancer, autoimmune diseases, chronic inflammation and pain and so forth.
08:39: Both of those baskets, which represent close to $7 trillion that we spend nowadays are in our purview. So, what are we working on and where do we see us? The three R's, as I mentioned, regeneration, repair, rejuvenation. In the regeneration front, we are very interested in the central nervous system. We have been actively studying models of things like traumatic brain injury and Alzheimer's disease, not just focusing on how we regenerate neurons in the proper structure and function, the proper morphogenetic structure of neural tissues, but at the same time how we can erase epigenetic reprogramming of those tissues, the earlier stage damage.
09:19: Because as you're aware, what are we learning nowadays? We're learning that Alzheimer's, yes, it's this horrible degenerative disease, but there's a lot of pathology that comes before we get to nerve regeneration. Whether that's classifying out timers is type three diabetes or an inflammatory disease, there are a lot of changes that are occurring in those tissues earlier on. So, we're looking at both sides of the equation there.
Dan Pardi - 09:41: At what point can this combinatorial biologic intervene does a condition damage need to occur, or are there wellness applications that are intended for prevention itself?
Ira Pastor - 09:51: I think the entire spectrum. We are looking at both in our corporate strategy. That we have disease interventions, we have late stage disease interventions in terms of recapitulating and regrowing neural tissue. We have the earlier stage sort of epigenetic damage that occurs in some of these tissues. And then very early, we think they are indeed health and wellness type interventions, whether they're supplements or functional type foods, that also very early on in the process in the sense that if we think of a long term metabolic dysfunction that can occur where we could also earlier intervene throughout the continuum of something like neural health. We think there are interventions on all fronts.
10:33: Obviously, a lot of the time we spend in the lab is at the far end of the research, but at the same time we keep our eye on these other things like you're involved with regarding to nootropics and what have you. So, these are interesting as well to us. The CNS is just putting my old school Big Pharma hat on. It's just such a unmet need not just with what we see in the world today, but with regard to what's coming in the next 10 to 20 years. When you see in last week, Pfizer fourth largest drug company in the world just abandoning Alzheimer's and Parkinson's research all together, that's a problem.
Dan Pardi - 11:03: Yeah.
Ira Pastor - 11:06: So, we really need to have new ways to address these issues.
Dan Pardi - 11:09: It's been a expensive and fruitless approach so far and perhaps we need a different approach all together to make some inroads.
Ira Pastor - 11:16: Yes. Other things that we're working on, so we moved from regeneration to more of the reversion front. We are very active in oncology and really the study of how reversion dynamics occur where tumors and oncogenic transformations can be erased and turned into normal tissue. This has been something that's been known for about 90 years now that actively regenerating environments, whether those are limbs of amphibians, or whether they are embryos. We even see the dynamic in the plant kingdom actively regenerating micro environments have a wonderful capability to organize in tissue that is healthy and organized out tissue, which is not required.
11:58: We have known about this cancer reversion capability for years. We just want to, with combinatorial biologic approaches, instead of looking at the kill event which has sort of been the basis of a war on cancer one with broad spectrum chemotherapeutic agents, and even now in war on cancer two with more of the sniper rifle smart drugs. In both cases, there's this missing picture that whether you're blasting away tumors with chemo or whether you're targeting specific cells, you still are missing a large chunk of the cells that are not attacked. Whether that is the ones that you missed in chemo or the ones that targeted immunotherapy are just targeted for.
12:33: We think an approach that is definitely beyond just us coming on stream, and there's a lot of thought leaders out there that are saying we really need a different approach with oncology, is thinking about the changing events, not the kill event which is secondary. But how we alter the epigenetics of that tumor in a broader sense to turn it back into a tissue that originally was or turn it back into the tissue where it now resides starting over normal healthy tissue. These are two big focuses of the company and what we've been active in regard to our internal research.
Dan Pardi - 13:06: Let's talk about your first generation Bioquantine. That's the first time I've introduced that term, but that is acronym for combinatorial biologics, Bioquantine (BQ-A), tell us about that.
Ira Pastor - 13:17: Sure. This is how everything began. The place, as I mentioned, where you find some of these reversion dynamics occurring, well most of them in humans, is in the early stages of fertilization following that event. In ooplasm or the materials that you find in the oocyte is where age reversal is found where the epigenetic, the genetic cleanup is found, and where all these sort of the morphogenetic determinants for that embryo are initially supplied to allow it to go on its forward journey. This is the reason why all of our children are born age zero, why children are not born with chronic degenerative diseases of old age. You don't have a baby ever born with Alzheimer's disease and why, for the most part, they come out with two arms, two legs, 10 toes and fingers and so forth.
14:03: We've been very active studying the whole dynamic of ooplasm reprogramming, which is another discipline that goes back to the 1940s. Dr. John Gurdon in UK in 2012 just received his Nobel Prize on this work, which goes back that far. However, since the 1950s it's remained sort of a petri dish concept. Been used for cloning purposes, been used for developmental biology experiments in the 1970s. However, it was never really leverage beyond that. And so, we are taking it the next step. Just like any other biologics derive from cell systems of this nature, we want to take the next level. How can we move beyond the petri dish? We are not a stem cell company. We want to say, "Okay, yes, this programming dynamic can be used to produce themselves and for cell therapy, but we wanted to move it to a different level." And say, "Well, there are very interesting potential candidates in these ooplasm mixtures that can create biologics. That's the direction we went.
15:01: Now obviously, we cannot work with human eggs. Why? Because human females only make a couple hundred during the course of a lifetime and they go for about $10,000 a cell for various purposes. So, we work off the garden research and focus on a species, specifically Xenopus Laevis frogs, which have been used by the pharmaceutical industry actually going back to the 1940s. That's a wonderful species which has been industrialized already, which has ooplasm and eggs that are very similar to human eggs, and which are industrial produced one and produce millions of oocytes at a time.
15:35: So, we can gather a much greater understanding of the dynamics and then also isolate, fractionate, purify specific peptides and proteins that are crucial in the process. That has been the path that we have taken today in creating these first-generation materials and what we're basing the initial program off of.
Dan Pardi - 15:56: So, there are hundreds of moieties and micro RNAs in the oocyte yolk. How are you determining the right combination of these intracellular contents to then have a healing and beneficial effect and humans? I would imagine that machine learning might be a part of your future business strategy.
Ira Pastor - 16:14: Absolutely. Actually, there's thousands of moieties that have been identified already over the decades in ooplasm. We fractionate, we do bioassay-guided fractionation, we do assays on purified entities. We do recombination experiments between individual [inaudible 00:16:32]. Basically, between my time in Big Pharma and biotech, I was involved in the phytochemical business. So, very similar to developing any therapeutic say from a planted source, where you may take an extract of a leaf and have 5000 or 500 small chemical endings in there. You fractionate, and you further decide from ecologic perspective and the pharmacokinetic perspective. What's useful? What is not? So, we do a lot of work at that level.
16:57: We do proteomics, we do microRNAs, we do a lot at the level of the minutia, but we do not forget that the power of it, just like the power of things in the phytochemicals business, is not always in the most isolated substance, but in the system. In the grouping of substance. We think we have, between the artwork that we've been doing the last several years plus, a lot of what comes before us and then we openly admit we are this did not start with us. This started decades ago and we are standing on the shoulders of some giants here that there are a lot of good clues already as to what makes a good combinatorial biologic. In certain cases, remember when it comes to some of these substances, even the ones who have been on the market for decades`, you don't always know everything.
Dan Pardi - 17:42: Sure.
Ira Pastor - 17:42: You have to, specifically, FDA is very interested in it, you have a good reproducibility system in terms of bioactivity, bioequivalents, pharmacokinetics, and so forth. Some of it, that's sort of the mystery of nature, right? The combinations and the unique systems dynamics that occur, you can't always break it all down. It's sometimes too complex to reduce. And so, we're sort of happy playing in that zone. We know it makes from a drug development perspective our CMC tech work a little more difficult. But at the end of the day, we think it offers us something much more unique in a very standard drunk system that has existed for the last several years.
Dan Pardi - 18:21: Have you been able to test your first generation Bioquantine in Vivo?
Ira Pastor - 18:26: For the last few years, we've been studying quite a few animal models. Mice, rats, rabbit, some cat work actually. Traumatic brain injury models, models of melanoma. Some initial work in the area of skincare. Some induced wrinkling and alopecia models. So, we're going broad looking at wide spectrum regenerative and repair capability. And then we have done some longer term teratological models. These are more multi-year long-term chronic administration studies in healthy animals. Because, you're giving some sort of long-term regenerative signal to a living animal. What are the changes that occur over years?
19:07: The fascinating change that occurred was that we had active substance groups versus competitors that live 70% longer. That's interesting. It's interesting side effect and obviously the ability to turn back age is found, and it will blossom. It's a side effect. It's something we would say as a rejuvenation company, we're interested in. We haven't done too much more on that front. But nonetheless, we think it's it shows that there are promising long-term safety and tolerability profiles that are popping up for us. So, we're happy to see that.
Dan Pardi - 19:37: Certainly, seems indicative of a safety profile if you can make an animal live almost twice as long. And actually, looking comparatively to other potential or factors of the aging process and improvement of lifespan and by 70% is really significant. So, that's really promising. I'm now wondering if that plus combination of things that might decrease nutrient singling, improve mitochondrial health and functioning, do you think that there's some synergy between the bio quarantines and then other strategies or is this sort of a better approach altogether, because it's more holistic by affecting that micro environment?
Ira Pastor - 20:06: I definitely think there's important synergies with all of those approaches. Now we've not been able to delve too much into those dynamics in the sense that we've been pretty focused on just that early embryogenic, morphogenetic stage of development, where there's weird biophysical dynamics that occur and biomechanical dynamics as well. We think combinations of combinatorial approaches potentially will be even better, we just haven't gotten there yet.
20:36: But definitely, whether it's autophagy or a nutrient signaling or just many of these other approaches, which I think are all very relevant, are going to be very useful. Now, age measuring mitochondria ... We know, although we haven't spent much time studying it that organelle remodeling is a crucial dynamic that occurs in the early embryo in the first couple weeks. That's required. Very early on, embryos don't like a lot of oxygen and then it ramps up. Yeah. The short answer is, yes, there's probably quite a bit of synergy that is worthwhile exploring on the longevity front as it pertains to those dynamic.
Dan Pardi - 21:11: You've done work in various animal models, traumatic brain injury, cancer, skin wrinkling, hair loss and there are also some indications of some gerontological application so improvements in aging. And early stage, you're going to be focusing more on cancer reversion and organ repair regeneration and transplant. Is that another area too?
Ira Pastor - 21:28: Yeah. Our main US centric clinical program as far as it pertains to the organ regeneration dynamic is in the kidney. This is what we have. We have a three-year plan for the clinic here in the US, and in there, we're focusing specifically on some of the orphan fast track indications. A lot of people that work in regenerative medicine are looking at sort of the larger picture today with stem cells in terms of the heart or the brain, kidney. Kidney disease, there's many small diseases that make it up. It is still an area of significant unmet medical need and we spend $60 billion around the world on either dialysis organ transplant with rejection drugs.
22:05: So, our perspective from an endogenous regeneration say if we can keep you with those degenerating kidneys from going down either of those paths and keep you away from dialysis or transplant, we've done something important. Because there's a major gap in between there and early stage interventions. So, we think that is another fruitful area for our own program, but we're open to the whole system. We're not afraid.
Dan Pardi - 22:27: There's just such broad scale possibility for this approach to affect really all organ systems of the body and then overall system health. So, let's move to two disparate areas. One is your work with ReAnima, and then talk about some of the current health and wellness possibilities of this technology. Let's start with health and wellness, because ReAnima is a moonshot I'd say. But what do you think is possible in terms of using this type of tech in helping people feel better and look better?
Ira Pastor - 22:52: We have been active for a little while now. We're just starting to get our feet wet in the commercial arena in regards to skincare. We have a couple partners there and we will be announcing a couple more that we're bringing online. But in those specific cases, there is just an interest out there, due to the combination of things we've been seeing in our lab in regard to, for instance inhibition of proinflammatory cytokines in terms of the epigenetic reset that we see in a variety of skin cell types in the in vitro models. The in vivo work we do, some of what we're seeing now as age related to hyaluronic acid, collagenase synthesis.
23:36: A lot of what is important in skin aging and ultimately skin beautification appearance has excited people. And so, we're not consumer packaged good folks as much as we are pharma people, but we understand the market and we understand the requirements. So, we are creating right now, and I have created, through partnerships, a series of skincare products that we're getting our feet wet with in different geographies. I have a partner in the Netherlands that is coming online, one in Thailand, and we're beginning to explore further markets for these opportunities.
24:06: At the same time, a couple years ago, we formed a small partnership in Russia. In the Eurasian Customs Unit, which include Russia, Kazakhstan and Bella Ruse. We got this approval as a functional food ingredient over there, based on some of the historic use of Xenopus caviar, let's say in Africa, which actually interesting enough from a ethnopharmacological perspective goes back into the year 1802, when the species with first identified and documented in literature. Where there are many cultures in Western Africa used it for a variety of purposes. From basic health enhancement to sexual health to use in modulating menstrual cycles of women in Africa. Because these eggs were originally in the 1940s used as our original pregnancy test in the United States. So that is a really interesting backstory here, but nonetheless they were consumed these foods in Africa.
24:57: And so, our partners in Russia were leveraging some of that in their maniacal research in the area of hypothyroidism, where we are seeing some very interesting initial results in our oral applications. Improvement in glucose control, improvement of various thyroid hormone levels. So, we are beginning to see the possibilities of where we fit in, in terms of functional nutrition, nutritional products and continually optimizing the oral delivery, which is far from perfect at this point in time. That's a still tough road but we are working on it and we are at least excited by some of what we're seeing.
Dan Pardi - 25:35: So, at least for the applications that are being explored or being commercialized, this could be a consumed pill or topical?
Ira Pastor - 25:41: Yeah. So, we have topical and oral formulas primarily in the form of liposomes, and once again combining with some natural protease inhibitors. We just want to keep it as a nice environment for these substances, so they have a nice ride with that hostile gut.
Dan Pardi - 25:57: Are their challenges with the regulatory environment in United States that prevents the commercialization of these substances here or can people in the United States get access to them if they wanted them?
Ira Pastor - 26:06: On the skincare front we have no problem there. Obviously, this is not a food substance yet that has been ingested by large populations in the United States yet, but we think there are some paths. Let's say around that and we're exploring that with our regulatory lawyers right now.
Dan Pardi - 26:22: Great. Let's move on to the ReAnima project. This is perhaps one of the moonshots I'd consider, and I'd love to hear more about what this is.
Ira Pastor - 26:29: This obviously got a lot of people excited when we first started talking about it last year. It is a very exploratory program, but it was designed initially to target an area of research that has gotten little attention, close to zero research dollars over the years. Namely, the severe disorders of consciousness and starting with the most severe which is brain death. Which is the main reason that we all leave the world every year and is the definition of death around the world in most countries. The whole brain definition where there needs to be irreversible loss of function and the cortex and the brainstem.
27:07: In some countries, they just use the brainstem definition but that's a different topic. So, basically, we sat back. There was a lot of public exposure to the concept with cases like a Whitney Houston's daughter Bobbi Kristina Brown and Jahi McMath in California that brought the topic to the floor. But we're sitting here as a regenerative biology company and we know two things. Number one, there's many species in nature whose brains can be destroyed, in some cases cut out entirely, that regenerate in perfect structure and function and are species entirely happy. This includes planarians, includes amphibians, we see metamorphic insects, we even see it in small mammals who hibernate for six months of the year.
27:46: Combine that with the fact that when you go into the literature, even though in 1968 brain death was labeled irreversible by the Harvard Ad Hoc protocol. There are many cases, a few dozen that you will find where there are cases of natural brain death reversion, primarily in very young individuals who maintain some type of neurogenic niche.
28:05: Lastly, you have the area of Living Cadaver research which may be unknown or unpalatable too many. But this is an area of research that has gone on in many countries, including the US for a few decades now, primarily for using humans that donate their bodies for toxicology, pharmacogenetics, pharmacodynamic studies, as well as residents to practice surgical techniques and test novel medical devices. We basically put this all together. We said, "Look, why can't we do something a little more constructive with the Living Cadaver research model with tools that we have in 2018? Because 1968 was a long time ago when we first defined brain death as irreversible."
28:45: Once again, it is a very early stage project but nonetheless, the goal is to using combination technologies, not just what we're involved with, but also stem cells and some of the more vital physical tools that are used in the ICU nowadays to stimulate coma and PBS patients. Can we put a combinatorial protocol together that mimics in essence what we see an epimorphic regeneration in nature, in organisms who regenerate their brains? In essence, here we are. It is very early stage and we've only taken some baby steps so far, but we feel it is a legitimate ethical area of scientific pursuit and the trickle down learnings for all disorders of consciousness, as well as the chronic degenerative diseases of the central nervous system will be affected by it. It is a moonshot let's put it this way, if I was to bet we'll solve the blurring of death well before we cure cancer.
Dan Pardi - 29:38: Wow.
Ira Pastor - 29:39: Now we work on cancer too, but I think death, unlike aging, which may have hundreds of things that trickle down to why we age, death is one thing. At the end of the day, the death of the central nervous system is one cascade. And if we can appropriately target it, I think we can have some really interesting impact in the coming years.
Dan Pardi - 29:57: But let's talk about a hypothetical use case of this. Would this be for somebody who suffered some brain destroying injury earlier in their life? So, they're relatively young and they have established brain death, or is this all sort of an end of full life application where you can keep an otherwise healthy older person functioning for much longer? What are the borders on this potential?
Ira Pastor - 30:17: The former, what you mentioned is the initial focus of the protocol. So, cases primarily aged 16 to 65 at the gray zone of deep coma and irreversible coma. Most of the people will tell you in the neurointensive community, it is always a gray zone no matter what they say. No, we are not talking about catastrophic trauma brain death that you might see in a war zone. We're not talking about time sensitive brain death. Right now, we are not focusing on brain death as sequelae of an incurable chronic disease. So metastatic cancer that there's no cure for leading to brain death is probably not an important subject or a legitimate focus at this point in time.
30:56: Now all that being said, putting us aside for a minute. The very concept of Living Cadaver support, basically these are individuals who have recently been defined is brain dead yet or on cardiopulmonary support and are also on nutritional and tropic hormonal support, potentially is a very interesting area for sort of a place in between death and somebody like cryonics. Where if you can really maintain these people appropriately and begin to think of some of the interventions. No, not interventions 500 years in the future, all that cryonics, but really begin to explore some of the things that we just have not explored as the medical community, there may be some very beneficial outcomes role of humanity. There may be some very interesting suspended animation related approaches to solve some problems related to Living Cadaver system.
Dan Pardi - 31:49: Imagine somebody that is been preserved end of their life, they couldn't go die Bioquantines are used in a regenerative fashion prior to reanimation bring somebody back to a healthy state then bring them back to life.
Ira Pastor - 32:01: Exactly.
Dan Pardi - 32:02: If the technology was that far advanced, then the Bioquantines could prevent the degeneration in the first place conceivably. But still, it's really very interesting work you're doing. Talk to me about a roadmap. When all things go as planned, what do you think they'll be able to introduce your first Bioquantine into the marketplace for disease condition? What's the thinking there?
Ira Pastor - 32:20: Okay. Splitting the company now into its various components. From a US drug development perspective, we have a three-year plan on the kidney indication to be in the clinic with a five-year point of registration for a sort of fast track working indication. So, put US now aside, we are a US company, but at the same time we are also very active in exploring and studying other geographies. Because as much as the US is an important market for us and it's where we are, we cannot ignore the fact that in today's globalized world of medical research and training, that there are other areas that we need to investigate.
32:56: When you see things in today's world, like the Harvard Medical School that is operating in Dubai, or Weill Cornell Medical Center in Qatar or Newcastle University operating in Malaysia, you begin to realize the scope of this internationalization of medical research. We are beginning to get active elsewhere. We have a partnership in Thailand, we have one in India, we have something shortly coming online in the Middle East. But the smart people will tell you that US is an extremely important market. But look, if you can save one year into the clinic in Southeast Asia or the Middle East or Latin America, it helps move the program forward, you have to do this today.
33:33: This isn't like 30 years ago where the pharma industry ignored the rest of the world. One only needs point out to what Merck did last year. A fifth largest drug company in the world signed an agreement with the government of China and they created basically in a tropical island where if you're dying of cancer, you can access Merck's immunotherapies that are in development today. This is unheard of when you think of medical tourism as sort of niche. But here you have the fifth largest drug company in the world partnering with the largest government in the world to do this. We really see other governments and regulatory systems doing things that are creative and are potentially we need to copy here sooner than later. We hope we can get the market sooner elsewhere, but we'll be announcing that when it's set in stone.
Dan Pardi - 34:18: Ira Pasteur, CEO of Bioquark. This has been a fascinating conversation. Excited for what you guys are doing and where you are. It doesn't seem to be a technology that we have to wait 50 years. It could be available within our lifetime to have a serious impact on quality of life, disease reversion, health maintenance. Thank you for all the work that you're doing to forward this and coming onto the HumanOS Radio today to talk about your work.
Ira Pastor - 34:42: I really appreciate it. I appreciate all the work you're doing and exposing the world to all the exciting things that are happening not just in our area, but all areas of health and wellness what I think you're doing.
Kendall Kendrick - 34:52: Thanks for listening. Come visit us soon at humaos.me.