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

[ Day one ] of the Bank of America Healthcare Conference. I'm Greg Harrison, one of the biotech analysts here at BofA. And today, we're lucky to have Sangamo Therapeutics with Sandy Macrae, Chief Executive Officer. Thank you for joining us. Let's move right into Q&A.

Please.

The Fabry program and the ongoing Phase I/II STAAR study, for those new to the story, maybe you could review the current status of the program, and how your treatment could be differentiated compared to standard of care?

Well, we're really excited about the Fabry program. We're best-in-class, first-in-class, and now only in-class as the other gene therapies have all dropped out or disappeared. So we've dosed 20 patients now, both in the dose-range finding and then the extension part of the study. And we're planning to go to the agency in the summer to confirm the design of the Phase III. And our intention is to initiate the Phase III at the end of this year and dose the first patients in the first part of '24. It's really important because Fabry is a relatively common rare disease. The patients on ERT have to go every second week for infusions that can take them up to 5 hours. And they're not getting all the satisfaction that they're seeking. And it's fascinating when you look at the patients in our study who were on ERT, how much better they feel once you add in the gene therapy, how they're SF-36, how they feel, scores go up, how they stay off of ERT once they're off of ERT. And then those patients who haven't had treatment yet, the naive and the pseudo-naive patients, are noticing for the first time a real benefit to their condition. So it's an important condition. It's a condition with morbidity, mortality. It's a condition that ERT has been a great solution up to now. But with gene therapy, I really think there's a future for these patients that is very exciting.

Okay. That's great. Now you're looking to go into Phase III soon. What would your ideal phase III program look like? And when will you provide an update on your interactions with FDA?

We would love to share details of the Phase III. But I think until we go to the agency and have that conversation with them, it wouldn't be fair. We spoke to them last year and got some really deep, thoughtful feedback from them, one of which was come back once you've seen a certain amount of time on the dose you're going to take into Phase III. So that's what's gating our going back. Phase IIIs are -- have 2 components to them. It's how can you get registration as quickly as possible, and how can you ensure as many patients as possible are contained within whatever label you get. And that's what our design is focused on. It's making sure that Sangamo gets this medicine to patients as quickly as possible. But it hits all the groups that are requiring it. So in the U.S. and Europe, there's different treatment modalities. There's men and women. There is patients with cardiac disease, with renal disease. So Fabry is a really eclectic group of a condition. And we want to make sure as many patients as possible get benefit.

Got it. Now looking into entering the market after the Phase III, what aspects of the treatment do you think you would like to emphasize through the Phase III that would put you in the best position to be competitive compared to standard of care at launch?

And by standard of care you mean the ERT that you get every second week where you have to get a 5-hour infusion? And that's the most interesting thing about this journey. We haven't yet understood how fundamentally different genomic medicines are. It isn't a case of do you want the blue tablet or the red tablet, or do you want something that you take twice a day versus 3 times a day. It's something that you go in for a single infusion and that's your treatment. And then we would hope and expect you then get long-term, years' worth of benefit from that treatment as opposed to your life being decided by having to go in every second week and have that long infusion. And if all we did was replace the convenience for the patient, I'm sure they would embrace this and endorse it. But the results we've seen thus far in the study for patients that were already on enzyme replacement therapy, they're getting more. They're feeling better than they did. They're suddenly sweating. They're feeling better and reporting that. But I think you need to listen to the voice of the patient. The fact that patients that were on ERT have come into a study for a genomic medicine says they're voting with their feet. They're saying ERT doesn't solve my problems. I'm looking for something better and something more. And I would then refer you back to the patients in the hemophilia trial where the benefit that they get and the difference in their lives is not blue pill versus red pill, it's a fundamental change. They no longer have to worry about factor, about bruising. They feel different. And that's what we, I think, and all the genomic medicine companies will offer them.

Yes, that's great. How do you think about durability of the treatment? And what would your target be as far as durability that would make you excited about the profile of the drug?

As -- the truth is as long as possible. We have patients out, I think it's 22 months was the last result that we've shown, and there's no sign of a decline in durability. There's a debate that has been engendered by the hemophilia data that -- from both BioMarin and Sangamo-Pfizer that suggests that there is something different about hemophilia A. And the assumption always was -- shows that this is not what you see for Fabry, and there's nothing like it in Fabry. All of the patients, both the naive and those on ERT have flatline benefit with their alpha-Gal. There is no sign of a decline in it. And the patients that are off ERT have now been off for months, almost a year now, and they show no decline in the benefit. What do the patients want? In the hemophilia trial, they've said, give me 5 years, give me 7 years and the benefit risk works. And I think what Fabry offers is a lot more than that. And if we can do that and they don't have to go for those infusions every second week for 5 to 7 hours, we offer them a real -- there's a real patient promise of a future. Now when we come back here 10 years from now, we won't be talking about gene therapy. We'll be talking about editing, and we're talking about new technologies that will fix the gene that the patient has. I'm absolutely confident of that. And so I see the gene therapies as a bridge to that future and a solution for patients that are eagerly looking for something more than ERT.

Great. That's super helpful. Let's move on to the CAR-Treg program. Could you just talk about the unmet need in the kidney transplant space, and how TX200 could be a novel way to address this?

So in 2018, we acquired a company in France called TxCell that is an expert in Tregs. And we've now dosed 3 of the -- 3 patients with TX200, which looks at patients with an HLA-A2 mismatched renal transplant and creates CAR-Tregs for A2, which we then give back to the patient and the only place that they have HLA-A2 is in their transplanted kidney. And therefore, the hope is that it will go there and it will control and suppress inflammation and eventually allow them to back off on their immunomodulation that they get as part of the transplant. We -- there's great animal data that shows that this works. There's great data in humans already in the one study where they would use polyclonal Tregs, and they show that expanding a patient's Tregs simply and giving them back suppresses that inflammation, allows them to back off immunomodulation. And so we're really excited to show data later on this year from this study. Now I want to be absolutely clear. In the initial doses, we'll be showing safety because many people thought, do -- are Tregs safe? And we've shown up to now, they're very well tolerated. And secondly, can we show target engagement? We're not going to show at the end of this year that the patients are off all of their medicines, but this is a journey, and the renal transplant study allows us to biopsy the kidney and see that target engagement in a way you couldn't do easily with multiple sclerosis. It's a model, but we also feel it's a model for a transplant area where there hasn't been any great developments recently, and patients want to not take the various immunosuppressives that they do. It's a bit like the story around the Fabry or around the hemophilia. They're looking for some way to walk away from their disease and live as normal life as possible. And we feel that the Tregs offer that possibility. So behind renal transplant, we have programs in multiple sclerosis and inflammatory bowel disease with near-term INDs that are in large indications. And it's a strategic choice we made at Sangamo to move from niche rare diseases, which is a very specific space, to larger high unmet medical needs where we can make a difference to patients and hopefully, a much more sustainable commercial model.

Okay. Great. Where would you see this treatment fitting in, in the landscape in something like MS?

Let's wait and see what the results are. I mean to be very, very candid, MS is a space with several medicines that provide benefit. But they're medicines each that come with their baggage and have to be given on an ongoing basis. What we are looking for is something that tolerizes the patient to whatever it is that's causing the MS and gives them a long-term solution from a single injection or very few injections, and that's the experiment that we need to do. We have so much incoming interest from a whole range of companies on our Treg program. They see the signs as cutting edge and exciting. They like what Sangamo has done and that We have GMP manufacturing. We have editing capability. We understand how to do INDs. And they want to know how they can get involved. There are 15 Treg companies now. And we're the only one in the clinic. We're the only one in the GMP manufacturing. We're the only one with an experience in INDs. And I really think that future -- for Sangamo the challenge is with all the interest in Tregs, how do we help people invest in our Tregs specifically and drive that program forward?

Okay. Great. Well, just a few minutes left, but I wanted to make sure and discuss the program you announced recently, which is the Nav1.7 program for chronic neuropathic pain.

Isn't that exciting?

It is, yes. I mean it's interesting the approach here because we've seen other attempts to go after this target and not a ton of success with blocking it, but your approach is very different.

Absolutely. They are not comparable. And having been in this industry for 25 years and done small molecules for a lot of that, the problem is specificity. Nav1.7 looks like Nav1.6 or Nav1.8. If you block Nav1.7 with a small molecule, you end up with cardiac side effects. I mean despite all the efforts of many companies, they've not been able to find a drug. We go completely in a different direction. We go to the gene. And the gene doesn't look like Nav1.6 or Nav1.8. And we're able to target a specific bit of DNA that's unique. It's the only part in the genome that the repressor goes to, and we turned off that gene. And we feel that we can deliver it intrathecally. We can deliver it specifically. We have the specificity of the vector of the promoter and of the repressor. And so we get a triple lock on specificity only for that gene. And if we can do that, we can go into a patient population. There's over 40,000 patients with the very specific form of neuropathic pain that we're targeting first. And we will give them relief from what is a life-altering, in some cases, life-ending form of illness. And that is the most specific group. And then there's a whole range of patients with similar conditions. And once we find if this works in that subgroup, we can move into others. We're targeting an IND next year with treatment soon afterwards. We have great results that we're going to show at ASGCT. And it uses the zinc finger platform that's been a core Sangamo for such a long time.

Great. What other areas could you go into with this approach of the epigenetic regulation and neurology down the road beyond pain?

There are so many areas that will be unlocked by successful delivery to the CNS. We have shown repressors for tau, for synuclein, for Parkinson's. We have beautiful data that we're going to show in -- at ASGCT on Prion disease. And there are just a series of diseases that with the right vector -- and I want to get people's head around the idea that it's vectors for courses. So it's not one vector will solve everything in the CNS. There'll be some that go for deep brain delivery, some for cortical delivery, some that will do better at the basal ganglia. And with the group that we have in Sangamo, we're evolving those vectors, we're talking to other people who have got other vectors as well, and we see there being like kind of Venn diagram of vectors and targets that will completely unlock the CNS in the very near term.

Great. Well, just about half a minute left, but I wanted to touch on something you mentioned, which is ASGCT coming up. What should we be looking for there? You guys have a ton of abstracts.

We have 14 abstracts reflecting the strength of the science in -- at Sangamo. And if I had to direct you to 3, it would be the Nav1.7 presentation, which really shows the remarkable signs that we're betting on; the Prion disease, which shows that mice live normal lives that would die otherwise from Prion disease; and the capsid evolution from David Ojala and his team that I think is the future of CNS delivery.

Great. Well, with that, our time is up, but I want to thank you, Sandy, so much for joining us.

My pleasure, Greg.