Morgan Stanley 19th Annual Global Healthcare Conference

Sep 10, 2021

Great. Good afternoon, everybody, and thanks for joining us for the next session. I'm Matthew Harrison, one of the biotech analysts here at Morgan Stanley. Very pleased to have Adigene with us for the next session. Before we get started, I need to read a quick disclosure statement. Please note that all important disclosures, including personal holdings disclosures and Morgan Stanley disclosures appear on the Morgan Stanley public website atmorganstanley.com/ research disclosure. So with that, please introduce Peter Lou, the CEO of Atagen. Peter, I know you want to make some opening comments, so I'll turn it over to you for that and then we can get into Q and A. Thanks, Mathew, and thanks everyone for your time. And today, I'd like to take this opportunity to walk you through a few highlights about the allergens. And here are the investment highlights. I'd like to walk you through the opportunities Allogene presents. First of all, we are a platform company and we have 3 platform around antibody engineering. And with these three platform, we have created 3 global clinical assets under the new body clinical assets, which is the agonist, 4 MBB agonist, ADG-one hundred and six and the CTLA-four antibodies against a unique epitope. We also have our 4th C body in the clinics, we call the ADG-one hundred and twenty six against CTLA-four targets and there were more coming around those C body coming from this platform. And we finally, we do have this Powerbody pipelines coming from the Powerbody platform. We recently announced we have 5 ID labeling programs and some of them are already well into the IND labeling process. And also we show some partnership and right now many around our platform with global partners and the domestic Chinese partners. And we also continue building our leadership team. So those are the highlights. And I like also and introduce the platform here with a little bit of details. Our new body platform is a technology allows us to target some very unique epitope and in this case, epitope conserved between mouse, monkey and humans. And this unique capital not only give us a broad species cause reactivity, it also brings some very unique biology about those targets. For example, the CTLA-four and the 4.1BB targets allow us to balance the safety and efficacy. And with our Seabody platform, we'll be able to only activate the antibody in tumor microenvironments. This will widen the therapeutic index or target like a CTLA-four. And with our Powerbody platform, we take advantage of the C Body give us to those modalities only allow those either Fc enhanced or the T cell engagers or ADCs, the kind of a modality only activate those powerful modality in tumor micro So those are the core technology we're going to use and help our partners and ourselves to create highly differentiated products. So these are the collaborations we have done so far. As you can see, the Cbody platform allow us to create a lot of partnership, especially in ADC modality with our global partner from the Japanese partner, Polave, ADC softwares in Sweden and the Exelixis in the U. S. And we'll continue this partnership and with some big global partners. And with our new body technology, we work with NIH, Celgene and GSK to create very unique molecules against those tricky targets on those unique epitopes. And we've also out licensed some pipelines to domestic Chinese partners and the 2 programs to the Sanxing group, One is about non targeted PD L1 and the level target about the other targets and enter into the clinics and we've also worked with Henry. So our 3 clinical programs, our ADG-one hundred and sixteen, which we shown here in these pictures compared with YIPPI in the purple colored one crystal structure, our green colored antibody in crystal structure here, a small change in the epitope with a big change in its biology and the mechanism of actions. We'd like to share with you some of that excitement in our clinical developments. And also the C body, which with the market binding side against the CTLA-four target, push that sort of window even much larger than typically can be achieved for this target. And of course, our 4oneBB agonist, we show here in the crystal structure, in the green colored one compared to the BMS molecule on the top and the Pfizer molecule in the bottom. Here, again, we show this new epitope can bring the safety and the efficacy in this challenging targets. And with the 3 clinical collaboration with Merck, we recently announced and in combination with KEYTRUDA and we're excited for this opportunity. Of course, the endorsement by Merck for the differentiation we're bringing in for the CTO4 targets even though they have an in house program and also the clinical program in combination with IP. And with our full-1BB agonist, again with KEYTRUDA, as you can see, we will be able to benefit from more extensive experience in combination with KEYTRUDA in the field. And also we're looking into those indications, which are still challenging for PD-one therapies. And those combination will be exciting as you can see we put it here, right? And the full 1BB neo body 116, we put it here. And I think this still was the only target other than PD-one, PD L1 shows monotherapy efficacy and a multiple indication in combination with PD-one. And was the only IL target so far clinical proven for its efficacy by itself and there was multiple combinations, there are still a lot of challenges with the safety for the Kanda approved therapy. In fact, there's only one approved modality so far for this target. And the challenge is really coming from the safety of the current molecule against CTLA-four. By hitting this unique epitope, we'll be able to come up a much more potent molecule, 5 fold higher than the EP head to head comparison and the 3 fold safety, GLP tox studies. And this is both improvement in safety and efficacy because of targeting this unique epitope to give us a benefit in terms of how to broaden these targets and how to come up with very strong Treg depletion. So that's a unique epitope, really allow us to come up a very robust preclinical and a clinical program. And we'll have announced we have both in the patients right now at 10 milligram per kilogram, perhaps the highest dose and so far same for the EP. And we clean up the DLT at a 6 MPK dose level. And so far, for 22 patients we dosed use our drug, there's no drug treatment related toxicity. For Grade 3 or Grade 4, we only observed 2 Grade 2 treatment related tasks. So if you look at the historical data for YIPI, the 3 NPK, the Grade 3 and the 4 toxicity rate is about 30%. And with the dose escalation so far, the 3 patients at the 3 another 3 at the 6 and one patient at the 10, we didn't observe any Grade 3 tox so far. So we think this safety profile definitely compare favorably with the historical data and we'll be able to report the top line data this year for the dose escalation and also the cohort expansion data at 6 MPK this year. The next program is our I basically just walk you through this very quickly, how we compare with EP head to head, right? At the dose level, 5 times we are basically 5 times more important than the EP here. And the mechanism is really the Treg depletion in the tumor microenvironment and a low defense in the PBMC and the kidney. And so this very strong ADCC effect compared to the YIPI and the soft ligand blocking compared to the EP in the green color that we showed here, the green color molecules. So our C Body program and with this masking and so far we have dosing about 10 patients and we are dosing patients now at the 3 MPK. And we'll continue reporting this dose escalation data about this C Body program and other things. And I have to say those clinical progress are very exciting for us for these targets have been known for years. And this C body, again, we show not only safe, they are also active against the tumor models shown here. When they combine with PD-one, they really shows a nice combination with PD-one like our new body and also the safety profile in that combination is also very robust in our preclinical models. Again, it's a Treg applications. So those are the GLP talks data we published and I refer to you to look at this data and the compare data published by BMS last year in the ASCO. As you can see, we'll be able to dose in the monkeys at 30 milligram per kilogram without the serious damage to the monkeys and the 200 milligram per kilogram our safe mosquito antibody. Those data compare very favorably with EP and the EP probody ADCC enhanced EP probodies. So our full MBB agonist. We have published extensively about our dose escalation data and they include some dose cohort expansion data. Again, we show this epitope here can make a difference in balance of safety and efficacy. We have to be able to dose cohort expansion at 3 and the 5 NPK much higher than other reported. And with this, one of the highest stable disease rate, the 56% for monotherapy, some partial response from our drugs. And we think we are making some breakthrough in this agonist antibody against these challenging targets. And again, we have published extensively for the PD markets we show for NK cell, soluble CD137 and the correlations with the clinical response and the predictive biomarker relate to this tumor shrinkage with proprietary biomarkers. And finally, our exciting pipelines about our differentiated CD47 in terms of efficacy and the safety and the issues related to other modality around these targets and our bispecific T cell engagers. And I basically while end up my talk here and put some major catalyst event here for your reference, and I'm open for some Q and A session. Thank you for your attention. All right. Thank you, Peter. I appreciate those introductory comments. Why don't we go through a couple of items. So maybe the first thing to start is with the NeoBODY CTLA-four. I think one of the things that you've highlighted in the past is about ADCC and that improving efficacy. So maybe you could just comment on why you think that's different and why you think no one else has done that in a target like this before? Okay. Yes. So Matthew, it's great. I think that this is really related to our platforms because as we show you here in our new value platform, we'll be able to come up with very novel design for antibodies. And we basically leverage what we call the AI powered antibody design platform. This really allow us to come up with design with the same sequence, but with a conformational diversity in the CDR regions. And what this allow us to do is this dynamic funding target allow us to engage target like a CTLA for in a very normal way. And this adaptivity not only creates the cost of activity, which are very challenging in general for antibody engineering. And also we show here the epitope we created here, right? And we created this epitope. This coming to blocking the leak and bandwidth between CTO4 and the CD8086 very different from the EP. And not only that, the same isotype IgG1, we show a huge difference between the ADCC effect from our antibody compared to the EP. Okay. Okay, that's helpful. And then I guess you highlighted sort of the dose levels that you're through and especially those dose levels compared to ipi. Maybe just remind people about how many additional dose levels and where you think you can get to? And then I think maybe more importantly, what that potentially gives you from a combination standpoint, because obviously the combination here is what everybody is interested in. Absolutely, yes. So currently, while those in the patient are 10 NTK, is our original highest dose we intend to do. But given the robust safety profile we have seen, we revised the protocol to build up to 20. So yes, and of course, in combination measures just like you mentioned. And in the field, what the people do is usually do one dose level lower than the dose you have a DOT current. So currently, we've already cleaned up the dose, right? DOT cleanup is 6 MPK. So we can do dose escalation at 3 MPK. But because we have dosed the patient right now at 10 MPK, if we clean up the DLT at 10 MPK, that means we should be able to do the combination dose at 6 MPK. Okay. Yes. Okay. Okay, got it. And then I guess the follow-up to that is obviously you have both the NeoBody and the SafeBody against the same target. Is there a reason that you take both of these forward or would you expect the Safe Body to have the same kind of efficacy as the NeoBody, but potentially because of the constituent activation be able to even dose higher? Okay. Yes. So absolutely. So we know our C body has a very good safety profile. This our PD window is so much larger, right, because we show you this GOP tox data here. At the 200 MPK, the monkey are perfectly happy. And so but if you look at the efficacy, our C body is not as part of the new body because the way we're masking it and activate it, right? But what we found is interesting is because given this large therapeutic windows, we can dosing the animal at a higher dose, for example. We can achieve the same efficacy just like our Lew body if we increase the dose a little higher in monotherapy. But what's interesting is, if you look at the combination, the same dose level, our C body and lot of other partners are the new body, but when they combine with the PD-one, low difference in the efficacy, the combinations. And then we also have beginning to show there's no patient higher because with this added safety. And we also have this flexibility to combine with PD-one with a better safety combination in these combinations and that allow us to adjust the dose and the flexibility again in that combination too. Because the endpoint is, we don't want to leave any efficacy on the tables, right, which has been an issue I've seen in a lot of EP label combination because of the safety concern even though we know the 3 NPK is a better combination with, say, PD-one because of the safety concern and people have to settle with a low dose, for example, YMPK, even longer duration, for example, in lung cancer, 6 weeks. Right, right. Okay. So then you're going to do combinations with both the SafeBody and the NeoBody with pembro next year. So I guess it sounds like you want to see if there's any differentiation between those combinations before you decide on which one may be the better concept. You're right. Okay. Okay, good. Good. Maybe can we talk about 401 and then maybe we'll have a minute or 2 for CD47. So 401 look, I mean, I guess the top question here is, you've clearly demonstrated activity previously in your data set, but you've also talked about a biomarker approach to enrich the population. So maybe just give people about a sense of the path forward here and what sort of data we should be expecting to get from the monotherapy studies? Okay. Yes. So for the monotherapy data and we start with in total, we have a dosing patient of 98 patients from both U. S. And Chinese patients. And then we do have a lot of PK and also other biomarker datas and not yet published. And so we because we will be able to fit the post population from the U. S. And the Chinese patients and we see no difference. And those population peak simulations also tell us the recommended dose for monotherapies and of course, the dosage was used for combinations. So those are data we plan to release in some major clinical conference about details about those data. And also I should say, right now, we're doing combination with the PD-one in China and in dose escalations. We have seen very strong T cell activations through that combinations. And of course, under this PK data and the PD data, also we have seen some very interesting observation from that model comes to the combos and for those PD market changes and dose dependent manners. And of course, the PKs goes with that. So we like to publish some of those data again in the major clinical conference. And I should say one of the excitement is about the biomarkers. And because those biomarkers were shown from basically the patient samples from both U. S. And China and some of the tumor type can reach extremely high expression levels up to say 40% to 50%. And it turns out those indications are more sensitive to PD-one therapies. So those are exciting combination studies we're looking into and of course, monotherapy studies in combination with PD-one. So those excitement we're pursuing ourselves and together with our partner like Merck because those indications are highly unmet medical needs. Okay, good. That's helpful, Peter. And I guess maybe could you also just comment on the competitive profile here, right? You've got 4 1b, PD-one, PD L1 bispecifics out there. You've got a range of there are people looking at 4 1b, IL-twelve, IL-fifteen agonists, right? There's all kinds of competition out there. So maybe just how do you think about the landscape? Yes. That's again, that's a very interesting area. And we do notice some of the PD-one or PD-one bispecific. We found that those are interesting because we're doing the combination in that space. And I think I mentioned so we I sort of will say we need to come back to the fundamental biology of the 4 1BB. I think that people should go to the bispecific space really based on the biology reasons why they use those bispecific. And this inevitably has to answer the fundamental biology about the four-1BB. What we shown here in our studies and some things we already published, our antibody targeted this unique epitope is blocking the ligand, large ligand banding on this epitope completely, not the Pfizer molecule, not the BMS molecule, if you look at the crystal structure published by them. So we know having a competitive ligand blocking compatible agonist to this target. So we'll be able to activate this target in a native ligand like fashion. So it's a kind of a safe and efficacious in that way. Of course, there's a cost linking fact, which I'm usual from say PD-one and other kind of targets. And that cost linking also an important factor people should consider. So with our antibody, we're trying to balance those things. And so we show, in fact, in monotherapy, agonist is safe, unlike so people worry about agonist that may not be safe. We show it's safe. It can be to coke expansion at the dose level like 3 and 5 MTK, no issues, right? But in terms of those bispecific combinations, we found that the GeneMab data are interesting, especially when they show some response data, the indications and so each indication we already know and the indication people don't yet quite know. And we put a lot of attention to those indications because those things could correlate with the biomarkers we found in our antibodies. And we do find some interesting correlations in those observations. And of course, we like to say if our combination data also shows consistent with those bispecific constructs. We have bispecific construct, but at the least in our hand, we didn't see any synergy from the bi specific construct compared to the combinations. Okay. Okay, good. Well, Peter, thank you for those comments. Maybe just in the last minute or 2, we can touch on CD47. And just I think for everybody's benefit, just talk about the differentiating properties versus the leading CD47 that Gilead has as well as Pfizer's efforts? Exactly. We definitely we found the Garence and also recent Pfizer video are very exciting in the space and together with others. So I basically want to think about several points. The first point I should say, if you look at the recent Pfizer deals compared to other CD47 modalities, I think one major difference is the recent Pfizer deal, they do show monosarapeutic effect with respect to our response rate, right, monotherapy. And while if you look at the most of the antibodies, they have marginal monotherapy effect, mostly through combinations. And we think it's important in the checkpoint space to demonstrate other monotherapy effect. Okay. That's the 4th comment. The second comment is about the safety. And we do I think we do low list. This safety profile has something to do with the epitope. If you look at the 47s and also others, they have shown a different epitope, maybe a safety profile different from 47 molecules and we saw the same the primary dose. And in our antibody, we show this level of epitope we identify shows very different safety profile in terms of hemoglutination and all those effect and we should have nice dose dependence. And of course, with our C button, well, we're able to come in to address those safety issues in an even more powerful ways. And also, we show a very, very favorable PKPD in our molecules in the monkey studies. And so we basically say not only you want to address the safety issues, you also have to make sure your molecules still has the efficacy you want to show. So with our C Body technologies and then we definitely can address those different Fc functional side, right? So this allow us really come up a molecule with the potency we want to see and still with the safety profile so much higher than we have observed compared to other things. And also and we've also addressed other antigen sync in a very robust way, so the robust PK and PD profiles. Okay. Well, good. Well, great. Peter, thank you for being here. Thank you for your comments. Very nice to see you. Thank you, Matthew, and thanks to everyone.