Sangamo Therapeutics, Inc. (SGMO) Earnings Call Transcript & Summary

Good morning, everyone. My name is Gena Wang, and I'm SMID cap biotech analyst at Barclays. Welcome to our 7th Gene Editing & Gene Therapy Summit. I would like to thank all the participants, investors, companies and especially our event team and corporate access team, who made this event possible. And with that, I would like to introduce our next presenter, Mark McClung, Chief Operating Officer from Sangamo. Mark, well, thank you very much for joining us today.

Good morning, Gena. It's a pleasure.

Okay. So maybe I will start with your Fabry program, ST-920. So maybe regarding your regulatory path, I know you just received the Fast Track destination, also expect discussion with the FDA to finalize the Phase III trial design in the summer. And so maybe a few questions there. Have you secured a date to meet with the FDA, yet?

No. So as you mentioned, we're delighted that we received a Fast Track designation, Gena, because as you know, part of that sort of signifies that there's still an unmet need in Fabry disease. So we're delighted with that and are very much looking forward to our discussions with the agency. The last time we talked with the agency was at our Type C meeting back in the first -- early actually, in early 2022. And since then, as you know, there's been some significant changes in the office of therapeutics with Peter Marks coming in and some of the other changes. So our team right now is actually preparing the briefing book to take to the agency. As we've guided, we expect to have that conversation in the summer. And we'll provide further updates once we've submitted and secured a date. But we are very much looking forward to that conversation and our team is preparing. You would have seen that we also just appointed a new Chief Medical Officer, Lisa Rojkjaer, and she's obviously working with the team just to evaluate and provide her input into that as well. So we're really looking forward to that conversation and a pathway forward for the Fabry program.

Okay. I think based on your prior interaction with the FDA, you seem pretty confident that you may not need to run an active control study. Any updated thoughts regarding that front?

No, I mean that's still our view. And the example I sort of give here is there's -- if you take a look at hemophilia A, right? There's Factor VIII that's available for patients with hemophilia A, yet the gene therapies didn't have to do a comparative trial. So I don't -- we don't anticipate us having to do that because we're not an enzyme replacement therapy. We're a gene therapy that has a very different mode of action. And obviously, the agency through the Fast Track designation feels that there's the potential of this therapy to deliver against unmet need. And so our approach is to go in and basically propose a study that will allow us to capture and hopefully improve the lives of patients with Fabry disease that are currently not getting the benefits out of the treatment. I mean, one of the things I continue to sort of remind people is that in our trial right now in the Phase I/II, it's interesting, right? That we're getting patients that formerly were on enzyme replacement therapy that are not taking it anymore, which are the pseudo-naive. We're getting patients for the first time that are having treatment, which are the naive patients. And then we've had patients that are on enzyme replacement therapy that still choose to enter the trial because clearly, they're not getting a full benefit out of their enzyme replacement therapy. And so again, I think it signifies that this gene therapy is a really exciting opportunity for Fabry patients.

Good. Regarding the Phase III initiation and also maybe future commercial, do you -- or have you already aligned with the FDA regarding CMC and the manufacturing?

So yes, we do have a CMC plan in place. And yes, we did have an interaction with the agency. And so we -- and we started to manufacture the Phase III lot. So we are ready to go for Phase III, and we'll carry that same process forward at scale for the commercial launch.

Okay. Since we talk about manufacturing, I wanted to ask you the AAV you're using. What is the percentage of the full capsid in your experience so far?

So we're using AAV2/6. And unfortunately, I can't answer the question in terms of the capsid fill. Apologies. I just don't have the answer to that.

Okay. No worries. So the other one is regarding the data update at the World -- of data update. Any thoughts on -- we do see some mixed kidney biopsy data. Any thoughts how you can streamline in terms of, say, patient selection to minimize the variability when you start your Phase III trial?

Yes. So it's still early days. And those 2 patients, as you pointed out, looked different. We still think that the one patient that had other disease involvement, it probably contributed to that. We continue, as part of the study in the expansion cohort, to take baseline biopsies for naive and pseudo-naive patients. And so as we make progress through the expansion cohort, in addition to picking up the safety and the evidence of initial efficacy, we'll continue to evaluate the biopsy data as well. And so although we haven't guided on when we provide an update on that, I think it's important to understand that we're continuing just to enroll in that expansion cohort. And although it's not gaining towards -- moving towards the Phase III, we still think it's going to provide a lot of information to allow us to do the final design of the Phase III program. And then obviously, we'll provide continued evidence of safety and benefit in these patients in addition to the Phase III trial.

Good. What would be your target percentage reduction in Gb3 in the kidney biopsy data?

We haven't guided on what the target reduction is. I mean clearly, what you want to see is a reduction of Gb3 buildup in the target tissues, including the kidney. And based on the data that we showed back at World, we're seeing evidence of that as well as also a decrease in the podocytes. And so we'll continue to monitor a variety of those things as part of the ongoing study as well as the Phase III study and hopefully be in a position that we can give a holistic picture of the benefits that we're having for Fabry patients.

Okay. And regarding the next data update, like how many patients -- like what kind of data package should we expect to see? And then when should we expect to see?

Yes, we haven't guided on that. I mean we'll make a call whether we provide an update before the end of the year or we wait until World next year. We haven't guided on that yet. So -- but we are continuing to gather data. Right now, the team is fully focused on preparing for the FDA meeting and putting in the enabling efforts for us to move forward with the Phase III program once we get that agreement with the agency.

Okay. Good. Now switch gear to your Nav1.7, that's very interesting new announcement as a flagship program in chronic neuropathic pain, and we did see the initial preclinical data last week at the ASGCT. So maybe the -- your quick thoughts on the preclinical data we saw, how that can translate to clinical? And then how would that help you to determine, say, the dose or the target?

Yes. So I was at the American Society of Gene & Cell Therapy last week and Mohammad, who presented for us, did a great job, and there was a lot of interest in the audience and some very good questions. The zinc finger transcription factors really target at the source of the mutant protein isoforms. In this case, our zinc finger repressors are engineered in order to reduce the expression of pathogenic pain and selectively repress expression of the mutant allele, allowing expression of the healthy allele. And the data that we demonstrated at that thing shows evidence of that, at least in the animal models. The goal here is that Nav1.7, which is a voltage-gated sodium channel expressed in the dorsal root ganglion, will be the focus of what we're trying to target for basically the idiopathic neuropathic pain. We're going to be looking directly at regulating the pain levels in several genetic disorders. But blocking Nav1.7 in dorsal root ganglion is expected to really prevent the transmission of pain signals to the brain. And so if we're able to demonstrate that like we have in animals in humans, it allows us to kind of regulate that pain, and we're really excited about this particular program. One of the difficulties in the past with targeting this is that, in many cases, the protein pockets that are targeted by, for instance, oral-type medications and things like that, they're so similar between the various Navs, like Nav1.6, Nav1.5 as an example, that you get a lot of off-targets that don't allow you to really drug them. And so this particular approach, we're really excited about, and we'll continue to move forward and hopefully generate some continued evidence both in the animal models, but more importantly, as we move towards filing the IND and getting this into humans.

Great. And then based on these data, like what level of inhibition do you -- will you target in human?

Yes, we haven't targeted that. But if Jason Fontenot was here, he would say that there's 2 things that we're looking at, right, is the kind of roughly what kind of per cell inhibition that we're getting. But more importantly, across the brain, kind of what is the down-regulation, if you will, in multiple targets. And so it's really -- we don't feel we need to shut it right off. We feel that we just need to dampen it down enough to stop that pain sensation from moving forward. And so we'll continue to explore that, obviously, through the dose escalation study when we get into humans to see what is the dose that's going to provide that coverage so that patients don't feel that neuropathic pain.

What route of administration will you be thinking about?

So it will be intrathecal, so into the lumbar spine.

Okay. Good. And then before you file R&D, what are the steps you need to do with the R&D filing?

So in terms of where our focus is right now, it's really completing the GLP tox studies. We're beginning to manufacture the supply for the Phase I/II trial and putting the rest of the regulatory packages together to support an IND, which we're hopefully targeting for 2024. So the team is really just trying to pull everything together to make sure that we're in a position where we can file an IND and get approval from the agency to begin to dose humans.

Okay. Good, good. Should we see any additional update before the R&D filing from the preclinical data?

We haven't commented on that yet. I mean the -- in the past, as we've continued to demonstrate what we feel is interesting and relevant data, as you know, we tend to provide updates on that. But we haven't, at this stage, declared that we're going to provide a specific update at any point in time.

Okay. Good. Quickly on your Treg program. I know you have 3 patients already dosed. Can you remind us the follow-up time and then the possible timing to report the data?

Yes. So to your point, we have dosed 3 patients. So as a reminder, it's a 3-plus-3 protocol at this stage, and we completed that low-dose cohort. The study actually is an 18-month study, and then patients roll into a 15-year follow-up. And so -- and I think as we've talked about before, Gena, once they receive their personalized TX200 therapy, the patients are obviously monitored as they normally would be after kidney transplant. And it's typical that around the 6-month mark, they get their first biopsy. And so as we continue to accrue data, we'll look for an opportunity to provide an update. We've guided that we're hoping to provide an update before the end of the year. But what we've done recently is proposed a different trial design, which would allow us to accelerate through dose escalation. We've had 2 of the regulators sort of agree to it. We're waiting in discussions with the third. And if that's the case, what's exciting about that is that it will allow us to dose escalate through the study quicker to define that safe but effective dose. And so we'll provide an update on that once we finish the regulatory conversations. But our focus is really to try to that proof-of-concept study. We think that the kidney transplant area is a primary to show the utility of the Tregs. And as you know, we have multiple sclerosis and inflammatory bowel disease targets preclinically. So it will help inform the progress of those studies as well.

Can you share the 3 regulatory agencies?

We haven't disclosed which agencies, but you can imagine they're the ones where the -- it's where we're recruiting patients in the Phase I/II study in Europe.

Okay, good. Okay, that's very helpful. I know we have 2 more minutes left. I wanted to quickly discuss on, I think, one program is a hemophilia A, your partner program with Pfizer, and the other quickly on your sickle cell program. So the hemophilia program, the -- maybe, any thoughts on the -- I think BioMarin likely will get approval end of June. And then regarding the Pfizer, your partner enrollment completion, any thoughts there and also the differentiated clinical profile will you be looking for?

Yes, so Pfizer has completed the dosing. So it's just a matter of following the patients. Now they've guided that in the first half of 2024, they'll share the top line data. And then in the second half, they will file the BLA, which is encouraging. I mean, at this stage, we have not seen the data from that Phase III program. But Pfizer remains encouraged by that. I think we'll have to wait and see the top line data to see if there's any signs of differentiation from the BioMarin program. Pfizer is well positioned globally to effectively compete in that space. And so we're really thrilled to have them as a partner, and we feel that we're going to have a competitive product for patients with hemophilia A.

Good. And then for your sickle cell program, in the past, you come and you wanted to seeking partnership, do not want to develop internally. Any update there regarding the discussions?

Yes. So there's a couple of things. So first of all, we are on track to dose the additional 2 patients that we've agreed in the study. And so we'll provide an update at the appropriate time there. We are active through the process in opening up conversations with partners. And if anything materializes, we'll be certain to provide that update. But at this stage, our commitment is to the patients in the Phase I/II trial, and we feel that this is a competitive product based on the data that we have in hand versus CRISPR, Vertex. And so we're hoping that somebody will partner with us and make sure this gets to the patients in need.

Great. Well, thank you very much for the discussion, and we look forward to all the updates later this year.

My pleasure. Look forward to it. Thank you, Gena.

Thank you.