CRISPR Therapeutics AG (NASDAQ:CRSP) Chardan’s 5th Annual Genetic Medicines Conference Call October 4, 2021 2:00 PM ET
Samarth Kulkarni - Chief Executive Officer
Conference Call Participants
Geulah Livshits - Chardan
Hello. And it's now my pleasure to introduce you to our next participant, Dr. Sam Kulkarni, Chief Executive Officer of CRISPR Therapeutics. Sam, thank you for joining us today. As a reminder to our audience, if you'd like to ask a question over the course of the discussion, just type it into the question box underneath the video player.
So Sam, maybe you can start off by giving us a couple of minutes of introductory comments on CRISPR Therapeutics, including any recent business highlights or pipeline progress and upcoming events that we should be looking out for.
Thank you, Geulah for having this conference. We've been at this conference now for a number of years and always enjoyed all of the interactions, and the firesides.
We're almost seven years into the formation of CRISPR Therapeutics now, and it's been an incredible journey bringing this powerful platform to patients. From a portfolio standpoint, we've been very fortunate to bring a number of medicines to the clinic that can have a profound impact on patients starting with CTX001, which is a lead asset targeted towards sickle cell disease and beta thalassemia.
The data we've shown so far with CTX001 shows the curative potential off a CRISPR based therapy for patients suffering from these diseases. There's a lot more to go on in terms of how this therapy plays out. But so far, we've been very fortunate to have our trials move at a very rapid pace. We'll talk more about regulatory interactions and what the bar there is, but this is positioned as a leading therapy for patients suffering from sickle cell disease and thalassemia with curative potential.
Beyond that, we have three other franchises or pillars to our company. One is immunooncology where we have a number of CAR-Ts and other cell types coming into play to treat both heme malignancies and solid tumors, and I'll talk more about our three CAR-Ts that are in the clinic right now. We have a regenerative medicine pillar where we're regenerating organs starting with the pancreas. With them, we have efforts ongoing with liver and other cell types, and this could be a whole new world in terms of how we treat diseases.
And then our in vivo franchise, where we have both programs directed to various organs using AAVs and lipid nanoparticles, and they're both making good progress, and we have half a dozen programs with in vivo approaches that can all get into the clinic in the near future.
So, quite a bit going on at the company. We're close to 500 people now. We should have our own manufacturing facility up and running in the next few months. And even in the midst of COVID, we've made tremendous progress and are well positioned to take advantage of this secular growth in cell and gene therapies to bring tremendous benefits to patients.
Q - Geulah Livshits
Great. Thanks for that overview. So, you mentioned the data in sickle cell and beta thalassemia. So, you and Vertex have guided towards a completing enrollment this year, so can you comment a little bit on how you're currently thinking about the regulatory path in the U.S. and Europe and what might be needed for registration in terms of the bar there? And again, when we might have more visibility on that?
Yeah. It's had a flywheel effect. I think early on, it took some time to enroll patients, but once people saw the data, which are remarkable in thalassemia and sickle cell with the early patients, you have more and more patients being interested, more and more sites that came online, and now we've enrolled and we in fact have dosed at the last disclosure with more than 50 patients. And while we continue discussions the regulators on the exact number of patients require for a filing package, and also the non-clinical aspects such as CMC, I think everything's trending in the right direction. I think at some point this year and early next year, we'll provide guidance on exactly what that means in terms of BLA timing.
But our partner Vertex had made some comments about potentially filing in the next 12 to 18 months, which will be a remarkable speed from the beginning of the program to get into that point of BLA for the first CRISPR based medicine.
So, I think, nothing specific in terms of regulatory interactions, but everything is progressing nicely and having the RMAT designation certainly helps and having frequent and regular FDA guidance. And similarly, the PRIME designation in Europe allows us to have that same level of frequent and productive discussions with the EMA.
Got it. Great. So, some of your peers have run into challenges in terms of aligning with European regulators on the value after approval for beta thalassemia, for example. Can you comment on maybe how do you think about the read across from that to your program with Vertex and to what extent maybe Vertex is better positioned to address those types of issues?
It's very difficult to say what exactly happened in the discussions that [indiscernible] may have had with the German regulators around the pricing of their product, but it's hard to draw conclusions from that in a singular incident.
I think it's very clear that these therapies provide curative benefit. It's very clear that patients are going to have significant extension of life, a significantly better quality of life and a productive life. And that's just from a value standpoint, and then from a pharmaco-economics standpoint, you're saving a lot of healthcare costs but not having to treat these patients every year. Thalassemia patients require transfusions every two weeks. Their sickle cell patients are hospitalized every month in some cases, and that is a tremendous burden on the healthcare system.
So, I have a hard time believing that there'd be any country or any society would say we don't want to pay for these therapies in the Western world. So, I think those discussions are yet to come, but Vertex has a lot of experience in commercializing drugs, especially rare diseases and not just in the U.S., but globally. And I think, we'll have to see how it all plays out. But from an execution standpoint, we're well poised to take advantage of the fact that we are the -- we have this remarkable data. It could be the safest therapy out there relative to lentiviral approaches, and we're able to bring it to patients in a high-quality fashion across the globe.
Great. So, maybe let's move on to oncology. You mentioned a number of programs are in the clinic now. You have seen some data from your CD19 program. And we'll see an update on that plus initial data on BCMA and CD70 this year, I understand. So, for CD19, can you comment on what you believe are the differentiating characteristics for the CTX110 program versus the other CAR-Ts in terms of the asset itself, the study design, or perhaps the data to-date?
Yeah. Happy to. I think first comment at a high level -- 20,000 foot level is, I firmly believe that cell therapies are going to be the main way we fight cancers in the future. We've now had a 60-year modern war on cancer where we're throwing the kitchen sink of chemicals at cancer, and all of these have led to this perception of all these cancer treatments being -- having such profound side effects, hair loss, skin issues, GI issues, everything else, which makes patients fearful of therapies. I think this is going to be a new war. We have smart cells that are the medicines that are programmed to go kill the cancer and do it in a safe fashion.
I came across a recent article in New York Times about how the new therapies are all – patients go in and talk about these new therapies. And they're like wait a minute, you are not talking about hair loss, you're not talking about toxic chemicals. You're not talking about a cocktail of drugs that are going to impair me for this whole time I'm getting treated. And I think smart medicines are completely new way of thinking about the fight against cancer.
Second of all, I think you're going to actually see -- I don't want to use the word cures, but you're going to see the potential at least to have a dramatic impact on these cancers, both heme malignancies and solid tumors using CAR-Ts or other cell types. It is too early to say whether T cells are going be better than NK cells, my sense is if the body is using all these cell types in combination to fight pathogens, we could use them in combination to fight cancers.
And so, we've made this bet in oncology with the notion that cell therapies are here to stay. They all need engineering and editing, and CRISPR is the best way to edit and engineer them. And if we can build threshold capabilities both from a clinical standpoint and a manufacturing standpoint, and we can cycle through -- innovate faster than everyone else, then we're going to be at the -- we're going to be the preeminent immuno-oncology company in this space.
And I think that that's the bet we made. Now, we've made a bet on three different CAR-Ts CD19 and BCMA, which are proven targets, and the idea was to show that the allogeneic platform works just as well as the autologous platform and then CD70, which is a novel target that gets us from this heme malignancies into solid tumors as well.
On CD19, I think you've seen data from autologous while their autologous therapies and three of them now there's more experience with autologous therapies. There's over a billion dollars in revenue with the autologous therapies. They're still somewhat pigeonholed into academic centers or centers that are able to deal with safety issues like CRS and ICANs, grade 3 CRS and grade 3, grade 4 ICANs.
And the question is how do you get it out from that profile into the community where majority of the patients are being treated. And I believe [allogenic] (ph) CAR-Ts can do that. Now you – bispecifics , you've seen some interesting data, but you're never going to get away from safety issues with bispecifics that you see with autologous therapies because ultimately they rely on the same mechanism.
And NK cells, I think are too early. Now, although, we have ourselves made a partner -- made a better in NK based with our partnership with Nkarta, it’s still early to say whether T cells and NK cells are going to be superior in killing cancers. We think both may be useful.
So, I think there's a -- not just a niche, but there's a strong unmet need for a safe, convenient cell therapy that doesn't have all the side effects that you see with the autologous therapies. And I think you can find that with the reasonable efficacy, I think it's going to be the predominant way in which you would treat lymphomas, CNS [indiscernible] lymphomas. It may take a little time to play out that way, but that's the predominant way you’d see it.
The advantage we have in terms of our CNC in CAR-T or some of the other players as well, which is, again, we don't use any -- our conditioning regimen and standard flu side conditioning. It's not enhanced conditioning, which would -- for the deplete -- the patient's immune system and expose them to infections and other side effects. So, I think, we may have hit the right balance between safety, efficacy, and convenience here that could position as well to be the leading player in the CD19 CAR-T space.
With BCMA, it's early days. I think we're moving our trials forward. You have to get to the right dose levels to actually get -- see the effects and see if where you can be competitive. Legend is certainly set a very high bar in the BCMA space in terms of response rate and CRA. And then CD70, again, you have to get to the right dose levels just to start seeing efficacy. And solid tumors certainly are more challenging than heme malignancies. And so far there haven't been any reports of efficacy of CAR-T whether autologous or allogeneic and solid tumors, but I think it's just a matter of time.
So, we're quite excited about to keep moving our programs forward. Not one, but all three of them and continue adding programs with other cell types and other targets using the chassis and the manufacturing capability and the edits that we have.
Got it. So, from your discussions with clinicians, thinking about these different modalities that are currently being evaluated to potentially treat, let's say CD19 cancers or BCMA or other areas where we're seeing this different approaches in development. What factors would they consider and prioritize and thinking about let's say if multiple of these different modalities get approved, what factors do they consider and prioritize and deciding which modality or asset to deploy?
Yeah. It's interesting. We've done a lot of work in this area, and I'm sure you and others as well, which is you get different answers based on the type of physician you ask. If you ask the academic physicians, primarily they're driven by efficacy and the top academic institutions, the top three or four, they have a better experience in terms of getting autologous therapies than others, right? But that's -- you're talking about 5% of the patient population there or less. Once you get past that into the big networks, like the Florida Cancer Centers and other chains that treat most of the patients. One, I think safety is paramount. You need to have a certain safety profile to be able to do this in outpatient settings and do it in community settings where you don't have -- where it's harder to deal with some of these side effects, right? So I think you need to be able to do this in a relatively benign fashion. So, that becomes paramount in the community settings.
The second is I think convenience is important. I don't know that a lot of these doctors want to wait a month or so to get in line and get autologous therapy. They want to be able to treat the patient a few days after they're diagnosed or have the consultation. And it's almost like a why not with allogeneic CAR-Ts if it's available, works with waiting for autologous parties. And I think the general investor mindset it's highly skewed, but what they're hearing from academic physicians, and I think this will all bear out over time. And as you compare and contrast, but we certainly are seeing very strong signals from the majority of the oncologists who are looking for a convenient, safe, and relatively efficacious therapy in to treat those implementation therapies that are positive. And then if you see some success, it's going to leapfrog autologous into earlier lines of therapy.
To your second question around the different modalities, I think again if those are the criteria, let's see how safe NK cells are in the long run. As you look at bigger and in the trials and compare and contrast the efficacy and safety, let's see -- everything matters. If you're combining these cell therapies with a different agent that matters, whereas the single agent. If you're having a complex conditioning regimen that matters. So all these things are going to come into play. That's going to dictate whether -- let's say a CD19 allogenic CAR-T is a $200 million product or a $2 billion product, but there's certainly a place for these drugs and how you develop and how you position it and what the data over time will make a big difference in how successful these products are.
Got it. That makes sense. So you kind of touched on this and maybe we don't have to delve into this, but for the BCMA program, in terms of the efficacy benchmark that you'd be looking at, is that, for example, what we've seen with the autologous programs.
Yeah. I think you do need to be close to that. I think, there -- while there there's some tolerance around the efficacy given the fact that's more convenient and potentially safer, there there's a limit to that tolerance because I think people want the autologous therapy, if it's that much better. Now that said, I think you do need to compare apples-to-apples. You need to compare the ITT population, the intent to treat population. The game that most of these players that are doing autologous therapies are playing is doing this modified intent to treat is not a true reflection. Not only that, by the way, that they use MIPT.
The second piece is oftentimes you're getting some of these sickle cell patients on allergenic trials because they've -- they don't go into the autologous commercially approved therapies, right? So there's -- if you put it all apples-to-apples, though, I think, then you'd get a better sense for what a comparable efficacy is. But I think you need to be somewhat close to that bar. But at least in the CD19 space, I think the numbers are all over the place for autologous therapies, but now you're seeing even YouTube videos talking about MIT versus ITT. I mean, that's a game they've -- that those players have played effectively. In fact, I've asked two or three investors directly, okay? What do you think is the CR rate for autologous therapy is? Everybody's talking about a 40% CRA and I think malignancies. It's not true. That's on an MITP basis. And I think until people wake up to that fact, which I think the oncologists will wake up to that fact before the investors do it in some cases. I think you're not going to have an apples-to-apples comparison.
Fair enough. That's a good point. And then, I guess one other question regarding some of the parameters in the oncology cell therapy space, so we get asked a lot and I'm sure you do as well. In terms of the -- how you're currently thinking about parameters like a persistence and durability, and then kind of on a connected point redosing.
Yeah. I think redosing is going to be powerful. Durability of response to the ultimate goal. I think you want to have a relatively high CR rate and then you want to have durable CR, right, that's ultimately the goal for these patients to get them into remission for a long period of time.
I think whether it's persistence that does it, or whether it's the upfront impact of these cells and their cancer killing is an open question. I think the field was heavily thinking about persistence two years ago, right? That was the only way you could get durable therapies. But since then, you've seen all of these cases of patients that don't have extended B-cell aplasia that are durable. So, what's happening there? These CAR-Ts and these CAR-Ts don't -- they may be -- they're at the low level -- autologous CAR-Ts are gone. And so I think that points to the fact that, if you have a lot of upfront cancer killing, you may not need a lot of persistence to get durable therapies.
And the other notion is redosing. There's this notion of redose upon progression, but there's also a notion of redose as a consolidation dose, which has an allergy and other players are talked about. And in those paradigms, if you dose once -- feel most of the cancer cells and dose again very quickly, you have a chance of eliminating every last cancer cell and that will lead to a durable response. And so, there's a lot more learning about how to apply the allergenic cell in a different -- best way possible. But with -- that one makes another point for me, which is these allo therapies are only going to get better over time because there's many degrees of freedom in how you optimize it. Autologous therapies don't have that degrees of -- the same degrees of freedom. And I think we're at the start of seeing data with allo therapies and what they can do. But we'll be seeing a different tune in two years from now -- from three years from now where I firmly believe allo will be the predominant way where they're going to cancer treatment.
Great. Maybe in next couple of minutes before we have to wrap up, I just wanted to ask if you can give us a quick update on the status of the diabetes program.
Yeah. We're moving that forward. And I think, we hope to get into the clinic this year, which should be the start of our third franchise. I think, we organized our company to four franchises, hemoglobin novelties, immunooncology, regen med, and in vivo. And I think getting diabetes to the clinic, heralds a new startup, a new franchise for us. And it's something we think -- if you think, allo, smart cells is the next big thing. This is the next, next big thing, right? Treating common diseases just by replacing organs, you're -- you have diabetes, gets you a new pancreas. If you have liver diseases, we'll get you a new liver. And I'm not saying it's easy. There are challenges and how to make this work and make this all allergenic. But if that paradigm starts working, you're living in a whole different way of thinking about medicine.
Great. And so, I guess more generally from a big picture standpoint, it's been a big year for CRISPR technology, both in terms of public awareness, data and sector valuations. So, where do you see the growth drivers in the space coming from as well as for CRISPR Therapeutic specifically?
Yeah. I think for the sector itself, I think there's -- you're going to see more and more funding flowing into the sector and more and more interesting data coming from various companies. No doubt sector is become more competitive, but -- and I don't think at the end of the day is we are the one player that wins it all. Either it's going to be very similar to the antibiotic space. They're going to be 25 companies. They're going to be two or three that become the genentechs and [indiscernible] of the world. And four or five others that creates a meaningful value and bunch that don't work at all and fail. And I think, it's not easy for investors to pick those companies, but I think we certainly are positioned at the forefront of the CRISPR wave.
I think we -- at this point in our labs, we do the classical CRISPR CAT line. We do base editing. We do other forms of editing. We will incorporate whatever improvement there may be or changes to how you use the technology, whether it's for gene disruption, gene addition, or gene regulation. But all of us in service of programs, we're not here as a -- not here as a shop that just tinkers with the platform and develop new toys. I think our mission is to make new drugs and transformative drugs at that.
I think a lot of people forget that being different doesn't necessarily mean being differentiated I think with platforms. So, for those who are jumping onto the bandwagon of the version 2.0 and 3.0, I would urge caution because you had many companies that claim to humanized antibodies and have the best antibody technologies in the late 80s and early 90s that amounted to zero drugs. So, I think ultimately the currency of value creation in our space, at least for us, and I see it is to make drugs that work for patients. And whether we use one form of editing or another, it ultimately needs to produce clinical results that are differentiated, not just different. And I think we are laser focused on that, especially given our balance sheet and the ability to put all that to work. And we look forward to giving you more and more updates on our programs as we go forward.
Great. Looking forward to those updates as the programs continue. So, I think that brings us to the end of our session, but I'd like to thank you again, Sam, for your participation for the discussion today.
Thank you, Geulah.