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Direction Hi, my name is Kosuke Minamihata and I'm doing the Technical Support Manager for marketing at PeptiGrowth.
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And thank you for coming to our, presentation today.
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And let me start, the presentation then now.
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So first of all, let me explain about an overview of our PeptiGrowth company and we are a subsidiary of the Mitsubishi Corporation and we are found Co founded by the Mitsubishi Corporation and also the PeptiDream by in 2020 April.
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And we are utilising the PeptiDream, IT technology called PDPS peptide discovery platform system to make the synthetic peptide that has the same function as the conventional growth factors and cytokines.
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And also we are, leveraging the global marketing network of, Mitsubishi Corporation.
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And we are, selling our products in the North America and the European region all over the world by using their, sales networks.
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So what we, providing here is once again I'd like to say there is the synthetic peptide that is that has the same function as a conventional growth factors and cytokines.
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The benefit of them is, they are totally made by the chemical synthesis way.
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So it's animal component free and there is no issue.
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There's no issue of the lot to lot activity variations and also the contamination by the endotoxin whatever.
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And it's very, suitable for the cellular applications.
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And also the stability of a peptide is superior to doing the conventional growth factors because it is in just a cyclic peptide and it does not have any tertiary structures.
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So it's very stable against the heat treatment or the degradation by the enzymes.
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And also the most important thing is, we do have been a large, synthetic facilities that can enable us to make a huge quantity of peptide at one side.
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You know, the maximum, capacity that we have right now is like 5 kilogramme per batch.
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So by making it such in large quantity, we can significantly reducing production cost so that we can provide our peptide at reasonable cost.
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So that, companies developing like regenerative medicine, cell therapy, or also, cellular agriculture and products we can contribute a lot in terms of, price cost wise.
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So let me move on to next one.
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So this is kind of overview of, what, benefit of our peptide like FBS or the recombinant growth factors.
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Those has a lot of issues like, quality homogeneities programmes and also the original the impurities like in some contents in animal components.
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And therefore not, suitable for using the cellular, I mean therapeutic uses or the cellular agricultural applications.
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And we are solving all of those, issues associated with FBS ordering recombinant growth factors by making the synthetic peptide that is in the form of cyclic.
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And because it is cyclic, the stability is really high.
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And also it is, chemically synthesised, peptide.
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So there is no issue of lots of activity variation and also the contamination from the normal component.
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And the stability is since long, it can long for long time in the main cultural condition.
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So you don't have to exchange your media every day.
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You know, when we, when you use our peptide. And so far we have launched, 7 products to the market since, 2020 of April.
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That includes the HGF alternative peptide and TGF beta 1 inhibitor peptide, and BDNF alternative peptide noggin-like peptide and BMP7 for selective inhibitors.
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Then these two, products are kind of not the alternative for the conventional growth factors.
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It's a kind of derivative of this Noggin-like peptide, which is BMP4 and 7 inhibitors.
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And recently we launched, VEGF alternative peptide as a new product in September of this year.
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And soon we will launch actually Wnt3a peptide as a PG-008, which was actually originally scheduled to do the press release on November 1st.
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But, since the delay of the patent applications, I cannot show the exact data today.
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That was kind of unfortunate for us.
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But I will give you some detail over, the upcoming growth factors later.
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So let me move on to explaining about one each product 1 by 1 to explain how our peptide were working and how it is beneficial to the cellular applications.
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The first one PG-001, this is HGF alternative peptide.
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We also it is c-Met agonist and in the nature an HGF binds to its receptor called the c-Met and they induces a dimerization of the c-Met and that dimerization is a kind of trigger for the all the cell signalling events.
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And our peptide PG-001 is to make most to make was made to, function as the same as, recombinant HGF.
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We selected out in cyclic peptide that can binds to c-Met by using it, PeptiDreams in PDPS technology.
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And then we connected the cyclic peptide with the appropriate lengths of linger at appropriate, position so that upon binding to this PG-001 to c-Met it can induce the dimerization of the receptors and do the also, cell signalling event in the same way as HGF does.
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So that's how our peptide agonistic ones work and the left down figures are the ones showing the comparable comparison result for the HGF and our PG-001.
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As you can see our PG-001 showed comparable activity to recombinant HGF in c-Met phosphorylation activity and also the new proliferation of the new HUVEC cells.
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And in since our peptide molecule weight is much smaller than the non commercial growth factors and in case of this PG-001, the molecule weight is about 1/16th of recombinant HGF.
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Therefore our product for example 2 microgram of our PG-001 is actually equivalent to 32 microgram or recombinant HGF.
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So if, take a look at the price of our peptide, two microgram is actually now saving at how much it was in the UK, it was like 400 GBP I think.
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Yeah, in the UK.
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But, considering 2 microgram is, 400 and maybe many people would say, and that's expensive.
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But, if you compare at the price of the equivalent amount of proteins, 32 microgram HGF, now that is the one we have to compare with.
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So I think we are setting the price at the really reasonable price to the conventional growth factors.
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And with this, PG-001 we have an additional data to prove its activity more deeply.
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And we asked the Professor Taniguchi in the University of Tokyo to conduct, cell proliferation and also the cloning assay of the IPSC derived liver cells.
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And the results show that, PG-001 and also the HGF basically the has the comparable in activity in proliferation assay and also the cloning assay.
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So actually this in Professor Taniguchi was, he was saying that he's suffering from the quality variation of the recombinant HGF.
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So now he said, he will shift his HGF to our PG-001 in the future.
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Now he's, preparing the publication for this with using this data.
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So soon we will have the publication I believe with using our peptide and the next one PG-002.
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This is TGF beta 1 inhibitor and which is an example of antagonistic peptide.
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And in case of this PG-002, the tag replacement will be the kind of, well, kinase inhibitors.
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And in kind of for the differentiation of the IPSC or in the stem cells into new specific type of cells, for example, like endodermis, people often use this like specific kinds of kinase inhibitors like A83-01 or an SB525334 whatever then the number is.
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And those, small kindness inhibitors just go into the immune cells and then interact with, receptors and to inhibit, it's signalling activities.
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But then the problem is their specificity is not really high.
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So that sometimes those in small kinase inhibitors will interact with other, type of cell receptors and that sometimes caused the cytotoxicity issues.
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And instead of using those, kinase inhibitors, there's a way to use antibody to block the TGF beta 1, signalling.
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But all of those, antibodies are available in the market is not, animal component free, product.
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And also it is extremely expensive.
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So that it's kind of, not ideal to use, antibody for the replacement of the inhibitors.
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So we are providing this PG-002 to inhibit the TGF beta 1 signalling in a very specifically it binds to the ligand of the TJ beta 1 and then blocks the interaction with its receptors.
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So the peptide do not go into does not go into the cellular membrane.
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So it is, it works outside of the cells, it just binds to the TGF beta 1 specifically so that, the specificity is much higher and also it's chemically synthesised.
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So it's animal component free and, we can provide it to at the reasonable price and, antibodies and left down.
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Figure 1 figure shows the comparison result.
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It's the anti TGF beta 1 antibody and our PG-002 showed them equivalent activity towards the antibody.
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And the next one is another kind of agonistic peptide PG-003, which is BDNF alternative peptide.
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And the mechanism of this in PG-003 is same as first one PG-001.
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But the target here is the track B in receptors and our PG-003 binds to this Trk B to, induce each other dimerization and that's, same, signalling activities as the recombinant BDNF and Trk B force variation assay.
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And also the reporter gene activation assay shows that, our PG-003 have, same activity as, conventional, BDNF month.
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And I think there is there are many, researchers here.
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So our peptide PG-003 it's more very specific to destructive receptors.
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And in the nature this BDNF can binds to also the low affinity receptors called P-75.
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But our peptide has no affinity for the P-75.
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So it's not the totally the replacement of the BDNF, but it is more, focused to the like appropriative, signalling of the BDNF.
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I believe our peptide is and for this PG-003.
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We have a lot of, application data obtained by our, CRO or our, outside of the company.
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We ask in Jiksak Engineering, which is based in Japan and they're providing like, IPSC divide, nerve organoid to do, they know like research to do the drug screening, application, stuff.
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And they conducted the cell, I mean, nerve axon, elongation experiment from the nerve organoid, which is a cellular, I mean steroid type, cellular structure of the nerve cells.
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And the results showed that our PG-003 resulted much longer and thick and, thicker, nerve axon bundles generated compared to, recommend on BDNF.
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The reason for this, result is that because our peptide is more stable than, recombinant BDNF.
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And during this, experiment, they didn't exchange the media for one week.
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Therefore, during that time, I think the BDNF lost its activity because due to the denaturation of the BDNF, but our peptide remained, active so that, it resulted much longer and thicker in another axis.
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And the next one is, we asked this experiment to conduct, asked CRO to conduct this experiment.
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We used SH-SY5Y by itself to see the how the nerve acts, nerve networks would form upon, reaction to the our peptide or the BDNF.
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The results show that, our peptide and also the BDNF resulted created the nerve networks upon, exposing to the cells to the our peptide or in BDNF.
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And so all of those result we presented here is just proves the our peptide has the kind of comparable activity not in terms of just basic cell signalling events or even the proliferation activity, but also the higher phenotypes of them cells.
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We our peptide can create, same result in such, level of an experiment.
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Yeah, PG-004.
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The next one is another kind of inhibitor activity peptide.
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And this is alternative for the Noggin, which is comprehensive like inhibitor for BMP series of, families.
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And our PG04 binds to BMP four and BMP 7 family just like similar to the Noggin and the interact blocks the interaction between the RBNP four and seven with its receptors and left down figures shows the inhibitory activity result for the BMP four and BMP 7.
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And comparing the activity of the Noggin and PG-004 like as you can see showed, same level with inventory activity against BMP 4 and 7.
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And from this, PG-004 during we, we were developing this PG-004.
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We could get, two peptide that has the selective inhibitor reactivity tools in BMP 7 and four.
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And then we launched it.
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We launched them as a PG-005 and 6 and those five and six are very, I think, unique, peptide, it's not an alternative for the conventional growth factors or cytokines, but it's totally new, functional peptide that can, that can selectively inhibit the BMP 7 and 4, signalling, which was not possible with, recombinant noggin with other, small kinase inhibitors things.
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So now we are, providing this peptide to the researchers who studies like endothermal and how that different, how cells would differentiate upon in BMP signalling.
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So maybe, those researchers would find out how to use, utilise this in peptide in the future.
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And this is a result for in PG-005 and 6, PG-005 is the inhibitor for BMP 7.
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It will inhibit BMP 7 at the same level as noggin.
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But for BMP 4, it has no, inhibitory activity.
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And PG-006, which is for inhibitor for the BMP 4 and it binds to the BMP 4 specifically and inhibited signalling.
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But for BMP 7 it has no inhibitory activity.
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So I think it's very clear, image, I mean result for the select me the activities and this is the latest our product PG-007, VEGFR2 peptide and the target is VEGFR2.
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And our PG 007 induces the dimerization of the VEGFR2 to give them a cell signalling and we confirmed with a specific, the VEGFR2 first reaction and also the proliferation of the IPSC derived the endothelial cells.
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And also we have another data showing that, differentiation showing efficiency from the IPSC into the endothelial cells within that data.
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I'm sorry I didn't bring today, but, our PG-007 showed superior activity than the conventional VEGF and recombinant ones.
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And yeah, those are the seven, products I have in just introduced now.
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And as upcoming growth factors, we will soon launch, Wnt3A peptide, which was originally, scheduled to press release on November 1st and it was delayed and we will do the press release on November 14th next week.
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And that activity is much better than recommended in Wnt3A.
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And also then it's much easier to handle compared to, Wnt3A recombinant one.
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Also the activity, we compare the activity with the CHIR small kinase inhibitor for them, which is commonly used for the alternative for the BMP3 signalling.
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But yeah, we achieved, similar level of self differentiation efficiency using the our PGs as well with which will be PG-008 our peptide.
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And as for the next one, I think we will launch EGF and then PDGF-AA.
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And basically EGF will be probably launched within this fiscal year.
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So maybe 2024, February or March, we can finally launch, this basically.
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And concurrently we are also developing other development pipeline listed here.
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So from the year of like maybe 2025 or so, we can have some of these, products into our, product lineups.
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And here today I brought some data for the basic candidate peptide ones.
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And so far, we have get the peptide, got the peptide that shows the Emax value 100% against in the human MSCs.
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And also we are now testing our peptides to the bovine satellite cells because we are now targeting, cellular culture, cellular agriculture, the industry as well because, in that field, the amount of the growth factors required is huge.
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And actually we have a little bit of update on this result.
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And recently we got, very good data on this, bFGF and 20 peptide and we achieved 100% of Emax value with the same level of dose against us, the recombinant against, bovine muscle satellite cells.
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So soon we will able to, launch, I think peptide to the market.
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And lastly, I'd like to explain about how our peptide are being made.
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We have another sister company called PeptiStar in Osaka city and they're the kind of CDMO company for peptide, synthesis and also, small original nucleic acid synthesis.
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And they are originally made to create produce the peptide API which is developed by our parent company PeptiDream.
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Therefore, they do have large facility that is, GMP compliant, facilities.
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And like I said in the earlier, they have the 5 kilogramme per batch scale, huge, peptide synthesis and purification systems.
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So that by utilising their large facilities, we can reduce, our production cost so that, we can provide our peptide at reasonable cost to the market.
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And this is a kind of last slide of our presentation.
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This is a summary of, benefits over using our PG peptide.
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The first of all, our peptide can be, can bring you then outsourcing cost advantage over the conventional growth factors and our peptide is much stable and also it is chemically synthesised so that it's at a more component free and GMP manufacturing also in assured.
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And also we can, ensure then the timely delivery.
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You know, all the manufacturing and also they've already is handled by within in Japan.
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So we can promise you and we can bring them peptide at the time of, rights time over your needs.
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Yeah, that's all.
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Thank you very much.
