OneSkin Progress Report | Carolina Reis, CEO Oneskin
5:00PM Oct 21, 2020
Today I'm super, super happy to have Karolina with me here. And are you here? Yes, I can see you. Catalina is for Munchkin. And I know that at least one person here in this group is actively, you know, let's say, functioning as your guinea pig. And so I'm super, super excited to have you and discuss one projects with the exciting work, I'm going to share a recent link to a recent talk that you gave at a recent online conference in the chat as well. I'm going to share and some more info on your organization and on yourself here in the chat. But this is kind of like the kick off of Community Update. So if you have another update after Catalina then go for it afterwards. But for now, Cortina, the stage is yours. Tell us about one skin what's new.
So thanks, Alison.
Hi, everyone. I don't know if everyone is familiar with what we are doing. And so what is skin has been working for the past four and a half years to studs teenage in biology. So basically, we replicate skin aging with 3d models. And then we can evaluate the chain sports and bait morphology and also the gene expression. And we have also developed a schema specific molecular clock that we can measure the age of those tissues that we grow in the lab. So similar to harbor has done we have been, we have built a clock that's specific for skin tissue, and then the accuracy is higher. And finally we have the Delta cell based screening platform to find the new centers that are building that therapeutic compounds. And we have validated those compounds in several models of skin aging. UVB senescence model and also replicative senescence and then we have formulated this peptidyl have evaluated first the safety in different studies of toxicity mutations is carrier typing skin sensitization. And then finally, we have formulated this peptide in a topcoat application that we have tested both in our 3d models and Nelsons x V with skin or skin biopsies. And we have seen an improve in the skin in their mo layer thickness. So we see that the skin gets thicker with the treatment. So maybe I can share my screen a little bit. I think it's easier for you guys just to visualize what I'm saying. Because I know that most of you are probably not familiar with skin models is a is a different model that most people use. And I can share this presentation later Ellison you can share with everyone. I will. I will skip the introduction here. But basically our focus is to find the news center therapeutic compounds to prolong skin health. And we believe that skin has been overlooked in this area of longevity, but it's our largest organ and plays a very important role in our health. Mainly as we age after you know 50 years your skin starts to deteriorate and to accumulate senescence cells and those senescence cells start secreting inflammatory signals that can compromise your overall level of inflammation. So I was keeping through the action and I will go to the part where we are replicating the skin in the lab. So this is just a comparison with the models that we grow with human skin biopsy, you can see that we are replicating the main layers of the skin, their arms and their arms and they strapped on carnian and then we can predict very well. Why do we test in vitro and correlate with the outcome in vivo. So we are not only replicating skin but also skin aging. So by using cells from donors of you know, a variety of ages, we can show we can replicate a very young skin, your native skin up to a very agent skin and we can see how they structure the morphology chains over aging. And we see also the gene expression related to markers associated with aging, inflammation, proliferation, extracellular matrix and we have been a huge fan of genes that we characterize those models.
This is a skin molecular clock that we have developed this is also available for research. So in this website malkani.com you can upload your data and you can use this clock to calculate skin biological age. And this is just a comparison with harvest clock skin and blood. And here we call the, when we validate if and this external data set, we could predict with a lower error, so a better accuracy and then we can use this clock to evaluate you know, skin diseases, conditions or treatments if we are reducing the biological age. So these are the markers that are used to screen this center therapeutic molecules we use a tr x for cy and also better galactose I days, that's a very well known marker for senescence cells. This is the screen that we have done very similar to what was published before, and they HSP 90 meters. So most of our molecules they they decrease the level of senescence, where they don't decrease the total cell number. They are more center morphix or then center lyrics if we compare with abt we see a huge decrease in the total cell number. This is the validation of our lead compound we see decrease the senescence cell burden by 25 to 40%. we validate in donors and different donors and we mainly use primary cells, and also cells that are not transformed. So are we use cells read from Roger, right patients or elderly donors. And any as we were doing those senescence with UVB radiation, so these experimental years show that we are increasing the dose of UVB we're increasing the levels of senescence into the different cell lines. And if we treat those cells after the damage, we prevent the accumulation of senescence cells to a very significant extent. And then this is trying to validate the mechanism of action of our peptide. So we see that we induce the DNA damage and then after treatment with the craze, some very classic DNA damage markers such as phospho gamma to x with decrease between one phosphor 80 and also any cap NF Kappa b. And this is so is decreasing this signs that perfect that are inducing two semesters to the production of SAS. So in the end, we have a lower accumulation of senescence cells. When we treat aged skeans, we for molecules, we see an improvement in the whole morphology, they store ology, and we can quantify these effects a schemes car. And we also have measured the scheme biological wage, and we have seen a decrease in this biological wage. In a large extent, if we compare it threatened like acid, that's a very common Maalik used for skin rejuvenation, but retinoic acid is usually associated with a lot of inflammation and other side effects that can be damaging your skin more in the long term. So these are the top coat treatment and skin next plans so these are real human skin when we treat a skin Stockley with this cream containing the peptide we see an increase in the dip in their mouth thickness. We've read now again, we don't see this effect, we see this upper layers coming out like a billing effect. And again, when we measure the biological age, we could see a significant decrease in this case, around two to three years of decrease after five day, five days treatment.
So these are the safety studies. I won't go through all of them. These are the proof of concept clinical study that we have done with treating patients for 12 weeks, and we have not only seen an improvement in several aspects of skin appearance, firmness elasticity, but we also have seen an improvement in the scheme area that's related to the main function of the scheme. And these shows a very good correlation With the data that we have found in vitro, in the in, and that's related to the increase of the epidermal thickness, lower amount of senescence cells inflammation and a decrease the biological age. And finally, we have tested this molecule in C. elegans show, evaluate if we could have applications beyond the skin. And we saw very interesting data showing an increase in the median lifespan. When we treated with one micromolar, by around 16%. And more interesting than that, they weren't they were more active throughout their lives. So if you see the control, the worms are very active in this, you know, initial days, and they start moving as they age. And we've always won treatment, they continue very active. And we saw any an increase of almost like 300% in some of the some of the groups. So this is more related to healthspan, then lifespan, and I think this is what really interests most of us. Yeah, here I have a short video just show how the worms here in the treated group, they move much faster than the non treated. And yeah, we are bringing this product to the market now in October, direct to consumer through our website. And here is our team. We have four PhD founders, and we have other aging experts in our team as well. And our marketing team that we are building right now, as we go direct to consumer, we need to learn how to communicate the whole science in a very effective and simple way. Board of Advisors. And that's it and happy to answer any questions. Sorry, I didn't know if it was too fast. But I know I was
awesome. Yeah, how much? How much is 111? Queen pot?
It's gonna be $120 for 50 ML, but you can also subscribe and then you get a discount. It could it could go to $100 or $79.
Okay, awesome. Any questions, comments on this group?
Yes, I want so I'm sorry, if you said this, and I spaced out, but I'm with the results on the on the worms really makes me now wonder, What do you know about the molecular mechanisms? what's actually going on with this compound? How like, Did it come from? And the secondary question to that is, is did the formulation come from a sort of first principles hypothesis about what you wanted to make? Or was this some sort of combinatorially thing where you finally found something that works?
Yeah, so I started for the bit by the second question. So we start we had we had this iPod hypothesis of targeting senescence cells on the skin, and then we need a library to start screening. So we collaborated with a professor that was researching anti microbial peptides. So we started with an initial library of 200 peptides, and we got to four hits. And then from this foreheads, we use an algorithm to do not random permutations, but that was a comparing the sequence that we're performing better, you know, again, the sequence that we're not performing well, we generated another 800 peptides, we screen them again. And then we go to five peptides and eventually we we decided to stick with AAS one. So now that we know that as always on decrease the accumulation of senescence cells Yes, that's our goal to understand the whole mechanism of action. So we hypothesize that Smar approved venitian effect in terms of preventing the release of SAS factors.
When because when we treated
cells from elderly donors, we don't see a lot of apoptosis. We're also interested in in evaluating outdoor for Jewish, we in the RNA seek we see some genes related to autophagy. But we needed to evaluate deeper if we are inducing autophagy, but we don't see signs of apoptosis very clear. When we those are sent essence with you b b. That's a more acute damage and then what we see it's more an increase of the DNA repair capacity. So, we are combining these different models but basically we are decreasing we are increasing the DNA repair capacity or the the paraphrase related to there. And then we add the creasing that paraphrase there are inducing the signal link to sast effectors inflammations and up to synapses. So for example, we have seen a decrease in TGF beta one receptor. So peptide they usually they don't have like one specific target that's going to link to only one pathway. So in the end is probably a combination of different scenarios that leads to this and the point of decreasing senescence cells and inflammation.
And one follow up question, Is this peptide naturally occurring in humans, or is it completely exogenous?
Yeah, it's a new and synthetic peptide. When we when we did the blast analysis, we found the homology of 70% of the sequency, but not 100%. So it's not completely naturally occurring in the body.
What stage are you at with fundraising? did you do? Yeah, you get delayed due to COVID?
Yeah, I mean, we raised the post seed round. So we are now pre Syrian say our goal is to launch the product, hopefully to get a good traction from the market and then re series in the next few months.