Transcript of the Corporate Update
Presented at the annual meeting on Dec 29, 2021.
Dr. West: Nafees, before you do, let me point out to those listening that the presentation can be found under documents in the top left-hand side of the page, and I'll walk you through the slide numbers.
So if you click on documents, you'll see first the cover slide, and then the forward looking statements.
So in today's presentation we'll be making certain forward looking statements that have associated risks and uncertainties, and so we refer you to our filings with the Securities and Exchange Commission for more detailed information about AgeX and its subsidiaries, including Reverse.
Slide 3, the mission of the company is, as it always has been, to target the rapidly growing markets in age-related degenerative disease.
We're doing that with this twin approach of the use of regenerative cells to regenerate tissue function, and this new technology iTR which will be the bulk of today's presentation.
On the cell therapy programs, Dr. Nafees Malik will now give us an update. Nafees, could you walk us through?
Dr. Malik: Thanks Mike. Good day shareholders. I'm Nafees Malik, the Chief Operating Officer of AgeX. It's a pleasure to be speaking with you today.
I will take you through some of AgeX's plans to evolve its business over the next year as cellular and tissue regeneration therapies come of age.
Investors and scientists are now excited about these therapies, and we believe AgeX is very well-positioned with its IP and knowledge.
This year, AgeX has had success in its collaboration and licensing strategy, which began in 2020.
I'd like to highlight a couple of things from 2021. Firstly, AgeX entered into a research collaboration with Dr. Kristin Stanford of Ohio State University.
She is one of the world's leading researchers in the transplantation of brown adipose tissue, or BAT, in preclinical mouse models.
We are currently working with her to generate proof of concept for AgeX BAT-1.
AgeX BAT-1 is a potential cell therapy candidate for diabetes and obesity.
The loss of non-shivering thermogenic fat, also known as brown or "good" fat in humans with age is associated with type 2 diabetes and cardiovascular disease.
The mouse studies performed by Dr. Stanford are evaluating if transplantation of AgeX BAT-1 in mice improves diet-induced obesity, metabolic health including glucose metabolism, and cardiac function.
She has now performed the first AgeX BAT-1 transplant in mice, and we should have data that we can share next year in 2022.
Secondly, AgeX licensee ImStem Biotechnology, a biopharma company developing human embryonic stem cell-derived mesenchymal stem cells dosed its first US multiple sclerosis patient with its lead mesenchymal stem cell investigational drug candidate, IMS001 at the Shepherd Center in Atlanta.
IMS001 was derived by ImStem from AgeX's pluripotent stem cell line designated ESI-053 under a non-exclusive sublicense from AgeX.
ImStem's IMS001 is in an early-stage human clinical trial, and in the future AgeX will be entitled to receive revenues in the form of royalties on the sale of IMS001 if successfully developed by ImStem and approved for marketing by the FDA or foreign regulatory authorities.
Additionally, AgeX will share certain other revenues that ImStem may receive in connection with the development or commercialization of IMS001 in multiple sclerosis.
Thirdly, this past month AgeX entered into a research collaboration with the University of California Irvine to explore the therapeutic potential of exosomes and other extracellular vesicles produced by neural stem cells derived from AgeX pluripotent stem cells with the goal of developing therapies to treat adverse neurocognitive effects of cancer, chemotherapy, and radiation therapy on brain function.
This research project seeks to address a critical unmet medical need that impacts the quality of life for millions of cancer survivors.
Research will be conducted at UCI under the direction of Dr. Acharya, who is an associate professor at the UCI Stem Cell Research Center.
This collaboration includes an opportunity for AgeX to license innovations and inventions that may arise from the research program, and to pursue clinical development and commercialization of therapies derived using those licensed inventions.
Exosomes are a highly attractive area to be in right now.
Looking forward, in 2022, AgeX will be expanding its collaboration and licensing model even further, with the aim of placing AgeX IP for product candidates and technologies into AgeX subsidiaries with value-add partners providing financing and potential co-development assistance.
The plan is for these subsidiaries to be independently financed.
Diversifying sources of financing for AgeX technologies and product candidates may permit AgeX to move a greater number of product development programs forward simultaneously.
Dr. Stanford at Ohio State University is performing a proof-of-concept mouse study for AgeX BAT1, which is being sponsored by AgeX.
If this is successful, we may have the opportunity for a third potential subsidiary that would focus on developing AgeX BAT1
[call cuts out]
In addition to this, we also plan to seek out strategic options of AgeX's UniverCyte, AgeX VASC1, and PureStem over the course of next year.
We are also exploring other ways in which we might acquire and co-develop or license technologies that will lead to the development of innovative cell therapies.
The AgeX team is very much looking forward to 2022 as an opportunity to move multiple cellular therapies towards the clinic.
Cellular therapies are coming of age now, and it is the right time for AgeX to exploit the foundation it has created in tissue and cellular engineering.
And with that I hand it back over to Mike.
Dr. West: Thank you Nafees, for that update. So if you follow along with me on the slide deck there on the left hand part of your screen, let's move to slide 5.
So we're going to be talking now about the subsidiary of AgeX called Reverse, and what I'll be describing are what is currently AgeX technology, but which we plan to have developed and commercialized through our subsidiary Reverse.
So Reverse's mission is to lead in the application of cell age reprogramming technology to precisely regulate induced tissue regeneration and cancer therapy.
So if we unpack that statement, there's a lot of detail there. Reprogramming cell age is actually possible today.
I'm going to walk you through some of the nuts and bolts of that, the basics of how that's actually true, and then how we have a technology to precisely regulate this age reversal to induce tissue regeneration, something that as far as we know is a proprietary technology to our company.
And then I'm going to describe, in a bit more detail than we ever have before, the profound cancer therapy implications of this.
I'm just frankly amazed at how powerful this technology platform is, broadly affecting diverse types of tissue regeneration, potentially, and diverse types of cancer.
We're quite excited about this. So let me quickly walk you through some of the science and some of our plans.
So if you follow along, slide 6, the opportunity is obviously aging and age-related degenerative disease. I don't need to belabor the point, I don't think.
Slide 7 shows the US census bureau data, and you'll see at 2020 we hit this inflection point where this tsunami of aging is hitting the shores of the United States and many other countries around the world.
And as I've said on many occasions, some 80% of the healthcare costs of the United States is due to chronic disease where the body cannot heal itself, like in stroke, heart failure, osteoarthritis for example, aging commonly has one or even more than one chronic degenerative disease, and this is what causes the vast majority of healthcare costs.
So there's a huge unmet need to find a way to regenerate tissues that are afflicted with chronic degenerative diseases, especially in the case of aging.
And that's exactly what iTR is all about.
These new technologies are transformational in scope, and exciting as it can possibly be.
The next slide 9, probably illustrates how thoughtful people are seeing this as a transformative technology for medicine.
Here are just some news reports and scientific papers.
On the left is Jeff Bezos, who invested in this company Altos labs, $270 million as a startup company in the space.
Calico, as I mentioned, Google's company, and the publication below Calico's logo there that they published in this space.
In the middle of the diagram is the Harvard paper that got the cover of Nature Magazine, which is one of the leading scientific journals in the world, turning back time in the retina to induce regeneration in the retina.
And then you can see also papers and other companies being launched in this space.
I think it's unprecedented in my experience, such a powerful start for an entirely new technology platform.
I think that reflects how thoughtful people see this as about as profound a new technology as you can imagine.
Okay, let's get into a little bit of the nuts and bolts and how this works.
Slide 10, so the red arrow illustrates the fact that our germ-line cells, our reproductive cells, continue the species forever.
But there's a fundamental difference in virtually all, if not all, of the cells in our body, other than those reproductive cells, the cells that branch out to make the skin and blood cells, and bone cells, and neurons, and so on.
Those are all called somatic cell types, and they undergo a restriction, or a loss of potential, and that leads to aging and age-related degenerative disease.
And I'm going to walk you through how we over the years dissected out how this works, and how we can intervene in it.
The next slide, 11, shows the first step in this restriction.
This was work that I and others did way back when, at my first company, Geron.
We found the gene telomerase and patented it, and showed that the loss of that gene causes the shortening of telomeres, which is a clock of cell aging.
So somatic cells in our body have a finite capacity to divide. It's called the Hayflick limit.
And telomerase is an immortalizing enzyme, and it's present in the germ line.
It allows cells to replicate, in the case of our germ line, for billions of years. So that's the first step, the loss of telomerase activity.
And then at my prior company, now called Lineage, I and my colleagues here at AgeX, and in the future, Reverse, showed that it was possible to completely reverse the aging of cells all the way back to the beginning of life, in what are called iPS cells, using a combination of reprogramming factorsó I'm showing you some of them there, SOX2, LIN28, and so onó and reset the lifespan of cells.
Slide 13 shows how scientists look at telomeres, those black splotches there on the left are one way of measuring telomere length.
And we showed that we could take cells all the way back to the beginning of life, and reverse, as we said, developmental aging, and restore the cells back to the immortality of the germ line.
That was the beginning of iTR, actually, in 2010.
On the right you can see subsequent work by Steve Horvath showing another kind of clock of aging, it's called the DNA methylation clock, that iPS reprogramming, these factors, could reverse aging of that clock as well, and I think the consensus today in the scientific community is these genes can reverse the aging of cells in essentially every known aspect.
Slide 14. The second step that somatic cells lose that causes chronic degenerative disease is the ability to regenerate.
In the first 8 weeks or so, the human body can regenerate profoundly, but we lose that capacity.
And so as an adult, if you have a heart attack, the heart just scars over rather than grows back.
Or cells in your midbrain lead to Parkinsonís disease, they cannot repair themselves.
If you have a stroke, you've lost your neurons forever, and they can't grow back, and so on.
Well, we call that the EFT: embryonic fetal transition. It occurs around 8 weeks of development.
Animals, slide 15, that can retain that regenerative state as adults regenerate profoundly.
So here on the left is a picture of the Mexican salamander, and on the right if we had a video playing, you'd see the amputated limb grow back in all of its complexity nearly perfectly.
And it's not just the limbs in these salamanders. Their brain can regenerate, their hearts can regenerate.
That's an example in nature of what we want to do in human medicine. We want to reawaken that biology in the human.
We call it induced tissue regeneration or iTR, and I think you can imagine how powerful that would be if we can implement this and bring this to the patient's bedside.
Slide 16 shows you diagrammatically how that would happen.
We would apply these reprogramming factors I mentioned earlier to transiently express them to take cells back past that embryonic fetal transition, EFT, to induce tissue regeneration, but not take cells all the way back to the beginning of life. So sort of take the train part way to your destination.
Some people call this partial reprogramming. So if you look on the internet and search the search term partial reprogramming and aging, you'll probably find papers that have been published in this space.
We call this iTR. It's essentially the same thing.
Slide 17 makes the point that our bodies early on are highly regenerative, because they're under construction.
As adults we lose that, and iTR is designed to bring in again the construction crew to allow the body to repair itself.
But the point on the top of the slide says iTR is pan tissue.
As far as we know, the mechanisms that turn off regeneration are common throughout the body, throughout the different cell types of the body, in the brain, in bone, in cartilage, in muscle, in heart muscle, in kidney, and so on.
And so that's what makes this platform particularly attractive to us.
Slide 18 shows just an example from our labs on hair regeneration using some of our iTR technologies.
On the top left you can see the control animal, and a combination of genes leading to complete regrowth of the hair in this animal in these representative pictures from our study.
Slide 19 makes the point about one of our patent families relates to a new way of precisely regulating this process.
We do not want to overly reprogram cells. We don't want to take cells all the way back to pluripotency.
We want to take them just past this EFT. And here is an example using a viral vector on the left, and then in that vector would be DNA, shown on the right top, where we have these genes that can take cells, like a time machine, back in time. And the switch that controls the genes, we've chosen a proprietary gene promoter or switch that will be on when the cells are in a non-regenerative state.
That's the point I'm trying to make on the right in the middle, where it says "Stops when EFT is reached."
These vectors are designed to stop reprogramming once regeneration is induced, and before the cells are taken all the way back to pluripotency.
We call this developmentally regulated iTR, or DR-iTR, and it's the subject of one of our patent families.
I have not heard of any of our competition inventing such a technology, but of course I'm not completely aware of everything that they're doing.
Slide 20 makes the point that we have filed early patents on multiple ways of introducing these age reprogramming factors: using gene therapy, RNA or DNA, or packaging RNA or DNA in exosomes, little envelopes so to speak, that the body uses to transport messages like a postal service would, throughout the body, and small molecule approaches as you can see in the top right, iTR 1547 which is a small molecule cocktail.
Now let me flip the coin over. Slide 21, you see this coin flip here on the left.
Aging and cancer have always been yin and yang in the minds of gerontologists, and now we think we know why.
Cancer utilizes some of these pathways in cancer biology.
So if you look in the middle of this page, 21, you see cells. This is meant to be a cartoon so to speak, or diagram, illustrating the origins of a cancer.
So here we have cells that are hyperproliferative when they shouldn't be, and what we have discovered--
Well, let me start with what the scientific community knows.
The scientific community knows that there are some cells that resist being destroyed by chemo or radiotherapy, and they call those cancer stem cells.
The current consensus in oncology is that those cells are a stem cell, they're more primitive.
I have a red X through that. We believe that's absolutely backwards.
We've discovered that what's called a cancer stem cell, these residual cells that are not killed by radiochemo, are actually the adult-like cell, and that cancer cells other than those have reverted back before the embryonic-fetal transition.
This, we believe, is a previously unknown hallmark of cancers, plural.
Like iTR addressing multiple tissue types in the body, we believe this unique signature or hallmark that we've discovered for cancer, is common to virtually all cancers, even lymphomas.
So gliomas, sarcomas of various kinds, carcinomas, breast cancer, colon cancer, lung cancer, and so on.
So like telomerase, it's a pan-cancer hallmark, and we have filed multiple patents on this, because we believe this is a really important new insight into cancer and leads directly to novel diagnostic and therapeutic strategies.
Slide 22 shows very briefly an example of one of those therapeutic strategies which we've invented and filed a patent on.
So here we're combining cell-surface proteins, at the bottom right you can see examples. These are from the clustered protocadherin locus.
These are proteins that are painted on the surface of embryonic cells, generally not in normal cells in you and me, but reappear in cancer.
So they allow vectors to be targeted directly to a tumor, and then on the top right you see what we call EPRO, or embryonic promoter-regulated oncolysis.
This is an oncolytic vector using a proprietary promoter, or switch, to drive a toxin.
And so when this gets into a cancer cell, it's designed to specifically kill a cancer cell, and specifically target a cancer cell, and target it for destruction.
This is a novel, as far as we know, and innovative approach to pan-cancer, to all the cancers that we've looked at, which is many different sarcomas and carcinomas.
Slide 23 shows a chart on the development. The plan with Reverse is to develop two therapeutics: Renelon, which will be initially skin application for scarless wound repair, and EPRO for cancer, and we're initially planning on developing it for breast cancer, but it could be, as I said, virtually any cancer.
On the near-term product stream, CardioStem I have not really discussed. It's a means of advancing development to make fully mature heart muscle cells for drug screening.
That and non-EPRO-related diagnostic uses of our technologies we plan to either partner or develop with a subsidiary, independently funded from the company, both of which have the potential to be near-term products.
Slide 24. We have the leading intellectual property and the most experienced team, demonstrably, in the sector.
Slide 25 just summarizes some of the things that I or my colleagues have done in the past.
The first isolation of human pluripotent cells back in '98, an effort that I led while at Geron.
And the cloning of the components of human telomerase, this first step in aging that I described earlier.
And then beginning in the year 2000, we showed that it was possible to reprogram aging using somatic cell nuclear transfer.
2005, I filed a patent before Dr. Yamanaka's paper, who won the Nobel Prize for iPS reprogramming, on an alternative method of reprogramming cells all the way back to pluripotency.
2010 is that age reversal paper we did, I showed you some data from, using iPS reprogramming technology.
And then beginning in 2013, our first, what I would call, thoroughbred iTR patent application, which is beginning to issue around the world.
We have another case filed in 2016, what we call the 075 case, and then since then 10 additional patents, both in iTR and iTM, which means induced tissue maturation. It's the opposite of iTR, advancing the clock in aging, for instance for CardioStem.
And we've filed extensively on the cancer aspects of this as I mentioned, I think in virtually all of those patent applications.
Slide 26 reminds us and puts in perspective iTR and regenerative medicine in general.
These are platform technologies. There've been several in the past.
Recombinant DNA led to the birth of the biotech industry. It allowed us to make any protein, even non-human proteins, using DNA, so that led to insulin and growth hormone initially.
Now a multiple billion-dollar industry of course, with Genentech and Amgen, and many other companies.
Then came monoclonal antibodies. Similarly, here you could make any antibody targeting any protein, like the novel coronavirus. Therapies have been developed using monoclonal antibodies.
But many other uses. These can be used to target virtually anything, to do all kinds of things, such as neutralizing infectious agents, or targeting drugs, and so on.
Regenerative medicine is like that. First with cell therapies, this whole field which I started back in the mid '90s, first at Geron.
The ability to make young, regenerative cells of any kind for the first time in the history of medicine, really was the birth of the designation "regenerative medicine" as a field, in a sense led to multiple billion-dollar transactions. I've listed a few of them there. It's come of age.
Now we have iTR, a new technology to induce the body's natural ability to regenerate itself, and to treat such a broad array of cancers.
This is a new category of regenerative medicine, which we intend to lead in the coming years.
Slide 27 summarizes what I've discussed today. We're continuing to lead in the innovation of novel therapeutics in regenerative medicine.
AgeX is developing, as Nafees discussed, BAT1 and VASC1, neural cells for Huntington's disease, to commercialize UniverCyte, and our GMP cell lines, and PureStem, and so on.
And Reverse Bio, which will initially focus on iTR and its application in skin, called Renelon, and breast cancer as an initial target, but we think potentially multiple cancer types using this novel technology we call EPRO.
So with that, that concludes our presentation. We very much thank you for being shareholders of AgeX, and we look forward to next year updating you on our progress at our next shareholders' meeting.
