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

Good afternoon, everyone. My name is Gena Wang. I'm SMID Cap biotech analyst at the Barclays. Welcome to Barclays 27th Global Healthcare Conference. It is my great pleasure to introduce Sandy Macrae, Chief Executive Officer from Sangamo Therapeutics. Sandy, thank you very much for giving us this opportunity. So before we dive into the questions, maybe if you could give a quick overview of the company.

So Gena, it's a real pleasure to be with you and to be with Barclays here. So Sangamo is a fascinating company. It's a genomic medicine company. It's a company that has the potential of 2 BLAs this year in Fabry and in hemophilia A. It's a company that we will be moving into the clinic in the summer with the first ever NaV1.7 gene therapy repressor. And it's a company that has evolved a fascinating capsid that at least 2 companies have now acquired, and we will then take forward into the clinic in '26 for prion disease. So Sangamo is based on a deep understanding of molecular biology, and the ability to use our zinc finger repressors and our delivery technology to focus the company as a neuroscience-neurology genomic medicine company. And that we see is a future where we can make a great difference to patients.

Great. So maybe start with your Fabry disease. And now we only have -- how many more weeks -- 2 more weeks in 1Q? I know in the past, you did say you will announce the deal for Fabry in 1Q. Are we still on track? I know Monday, you will have earnings. Should we still expect some announcement in the next 2 weeks?

So deals happen when they happen. And we are in late phase and deep discussions with several parties. What they see is an asset that should have -- that will have a filing later this year, an asset where the last patient 1-year visit is in April. And once that data comes, we will file for accelerated approval as the FDA has guided and file that in the second half of this year, allowing us to launch in the second half of next year. So all of that's on track, and we continue to drive forward to make sure that the Fabry asset is as prepared as possible for the file and launch. I think it's important to step back and remember that the decision by the agency to allow us to file with accelerated approval came in the very latter part of last year. And although Sangamo had prepared for a file 3 years hence to hustle to get all the things done for a file this year is a major piece of work, and I want to pay great credit to my staff in the clinical and in the tech ops group for all the work that's been done. It complicates the business development discussions simply because there's so much for them to absorb in a short time. We still have confidence that this deal will happen, and we have some interesting parties that are very interested in what is an important asset, and let's just rehearse what they see in this asset. We showed the world data from 24 patients at 1 year -- sorry, 23 patients at 1 year, 11 at 2 years where there was a statistically significant improvement in the eGFR compared to their baseline. We believe that we can demonstrate a significant difference to the effect that would have been seen either without or even on ERT treatment. But what the agencies see that they are so -- they find so appealing is it's an improvement in the renal function. It's an improvement in the SF-36. And the SF-36 is that quality of life that the health payers will find very useful for valuing the product. It's an improvement in the pain score. It's an improvement in the Fabry FOS-MSSI. It's testimonials from patients saying that they feel better. 18 patients that came into the study on ERT, all of them are off. The whole -- as a whole, we've been treating patients for over 4 years now where the alpha-Gal remains physiological or supraphysiological. We have been 18 patients off. The longest patient off now is over 3 years. So this is really a remarkable medicine that will make an enormous difference to patients with Fabry. And we hope in the hands of the right partner, we will be able to file it at the end of this year and launch it in '26.

Okay. Before I ask a specific question, I just want to confirm the deal term announcement was still happening in first quarter?

As I said, deals don't always happen exactly when you want. And so we want to make sure we do the right deal with the right partner.

Okay. So that means may have some delay on that?

It may move into the second quarter, but we're absolutely clear it has to happen soon. Absolutely clear because we need the funding to push forward our other projects. We're absolutely clear that it has to happen soon because with the BLA -- the pre-BLA meeting in the summer and then the filing by the end of the year, the partner needs to get involved in it, and I want to reiterate what I said before. There are several people involved in important discussions with us. And I will make sure that deal happens at the right time.

I think there's another reason. I think I previously talked about 1Q is because you do only have a cash runway through 1Q '25. So if the deal term, say, got a little bit pushed out to 2Q and how the cash situation will be resolved?

Gena, as we agreed before I came on stage here, we have our quarterly call on Monday, and we will talk about our cash runway on Monday. But we also have -- as you know, we've done 2 deals last year for capsids, and we are in significant discussions on another capsid deal. And that allows us to achieve the runway that will allow us to have time to do the Fabry deal.

Okay. Good. So now go back to Fabry. And I think you will have quite a lot of data in first half '25. You will have 32 patient data, right? So maybe -- and we did see the eGFR slope improve significantly from the initial, if I recall correctly, the 7, 8 patients -- no, I think 10-something patient to the 18 patients, significant improvement. And now with additional patient data and giving the right dose, should we expect the eGFR slope where we saw the last update will have a further improvement?

I think we're adding more patients and the signal is remaining, and I've seen more than you have from the world data, and we're confident that the -- it's not a signal, the effect. The effect on the eGFR remains, the effect on the renal function in these patients remain. From a Sangamo point of view, there's only 2 more patients, I believe, I've got to get to the 1 year, which is happening in April. So we are very confident that this benefit to the patient on their eGFR and then the renal function will remain.

Okay. The -- so when -- I think you already aligned with FDA on accelerated approval path. And can you walk us through like what they wanted to see in order for approval -- accelerated approval and also for the full approval?

So accelerated approval is approval. And I think we all -- I think it's worth restating that. Accelerated approval allows you to launch the drug and to commercialize it without restrictions. What the agency said very clearly is we would be able to get accelerated approval if the benefit to the patients on their eGFR was demonstrated in the 32 patients at 1 year, and we are very much on track to show that. The agency did not require or did not and did not ask for an additional study. And I think people get confused about accelerated approval, meaning an additional study. It doesn't. They may, at the pre-BLA meeting, ask for more data from the data package. So I think it wouldn't be unreasonable for them to see all patients at 2 years, but they haven't even required that thus far. We would be planning to make sure they're aware of that data, which is sometime in the middle of '26.

So my understanding in the past was if you show 2-year data, you could convert this to full approval. Is that correct? Or was it my misunderstanding there?

That will be a pre-BLA discussion about how they do it. But in the minutes and one of the very senior FDA advisers that we got to look at the minutes said he'd never seen such clear, concise recommendations from the agency. They said, to get accelerated approval, we would be required to show 1-year data for 32 patients. At that time, we'll also have 19 patients that will have 2-year data. So it is quite a body of data. And then the agency's next sentence was you may choose to submit 2-year data to demonstrate the continued clinical benefit. And so we expect that it will show the 2-year data when it is fully matured. But I can tell you that the 2-year data that we've seen so far continues to demonstrate a benefit to the patients. And what we've also seen is that the 1-year data predicts -- for each individual patient predicts what their 2-year data is. So we're very confident both that we will show good 1-year data and that if we're required to show 2-year data, that should also be positive.

So for the -- when we look at the eGFR slope, that was like super impressive. We're talking about 3-point something from previous less than 1, right? So it's very impressive. So did the FDA say something of statistical significance in terms of the slope? It's more the endpoint, 12 months -- sorry, 12 months endpoint compared to the baseline.

So they have given us...

Can we have the back one noise turn off?

The agency gave us -- we proposed how we're going to analyze this and the agency agreed. And we will analyze it both as the totality of the data to form the slope. So it's not one point versus another, it's the totality of the data. And we also will do appropriate meta-analysis to compare it to what happens normally in a Fabry patient and what is in the literature for Fabry patients on other forms of treatment. We -- and the agency has given us guidance on how we should look at those.

I see. And when you -- the BLA package, when you submit, what kind of data will be included in that package?

The totality of the data.

So that will be from the -- including comparison to the natural history.

We will compare it to what's in the literature for the natural history and what's in the literature and submissions from the various ERT treatments that are available.

Okay. Good. That's very helpful. And then with the first half update, any other safety surprise we should be expecting?

I think it's not -- the delight rather than the surprise is how well tolerated this is. We've now dosed 32 patients and haven't had any safety events that were related to treatment. The patients do not require steroids, and they don't require either prophylactic steroids or steroids because of liver events. It truly is a really well-tolerated medicine. And I think that will make it the medicine of choice for patients with Fabry. And clearly, patients who are on ERT would like to get off of ERT. But this is also one, I think, will be available for patients as potentially the first treatment of choice rather than ever having to go on ERT.

Okay, good. Before switch to your internal program, the other internal program maybe quickly, any update on the hemophilia program?

We're working with Pfizer to understand the data. I think people do not appreciate the volume of data and data sets that are involved in such a transfer. So we've only recently started to see what Pfizer had generated, and it's an enormous amount of data. And I will say again, the clinical team at Pfizer did an excellent job. What we discovered is they were days from submitting both the BLA and the EMA days. And this is a package that is ready and approvable, and we need to find the right way to take it forward. And we've initiated a process, which has just started. And we will work to see if there are people like us who feel that this should be an option for patients with hemophilia.

Any of the party that already show interest?

We've had -- I think it's 5 or 6 companies have approached us. I'm not sure this will be a large pharma company. I think this is an opportunity for a specialist pharma company or a rare disease company.

Okay. Very good. Given how long it takes for the Fabry deal discussion, I assume this also will take a pretty long time. And by then, like are you planning to complete transfer from Pfizer into your hand then hand over to the new partner?

That's a matter of discussion because that might be quite an inefficient way to do it. The ideal would be to transfer it from Pfizer to the partner. And so those are discussions that we're having with Pfizer.

Okay. Good. Okay. And then regarding the Pfizer data, were you able to get access to all the full data package so far?

There is a very clear contract about what they have to share with us.

Okay. Okay, good. Okay. Now quickly on your NaV1.7.

Yes, which is very, very exciting. I know everyone wants to hear about the Fabry deal and the hemophilia. But the thing that I think is enormous credit to our scientists and our clinical team is that in very few months, we will start dosing NaV1.7 for neuropathic pain. This is a program that was developed before we had our own blood-brain barrier crossing capsid and uses AAV9 given intrathecally to deliver a zinc finger repressor to NaV1.7 to the dorsal root ganglion. So each part of that is something that has been shown to be effective in other hands. So we know that intrathecal ensures that you get delivery to the spinal cord. We know AAV9 transduces the dorsal root ganglion. We know that the zinc finger repressor turns down NaV1.7. We know NaV1.7 is intimately involved in the pain pathway. And so from a kind of biological risk, this is a very logical thing to do. So we will dose in a dose range finding study with 3 doses, each cohort having a placebo patient or a sham injection patient. And we will hopefully accumulate data by the end of '26.

And what is the initial indication?

Idiopathic neuropathic pain, small fiber neuropathic pain, and there are a lot of these patients out there, and they really struggle to find medicines that can control their pain.

Okay. And I wanted to hear your thoughts on the recent -- the Vertex, the blanking out the LSR failure in terms of neuropathic pain, but that's a chronic pain and the failure. Any thoughts you're thinking will be questioning about NaV1.7 as a target?

So NaV1.7 and Nav1.8 hit different parts of the action potential. NaV1.7 is part of the initiation and the propagation of the action potential is Nav1.8. And we could have chosen either because for us, it's simply a bit of DNA that we would be binding to. When we spoke to -- when we took really serious advice on this, they said that they thought Nav 1.7 was, a, the most important target to go for and also one that nobody has been able to drug with a small molecule. And that's simply because with a small molecule, there's similarity to other channels and you end up with off-target cardiac effects. Just to reiterate, again, because I know you understand this, but the zinc finger repressor is aimed at the DNA in the promoter section of the channel. And that is a unique piece of DNA that doesn't look like any of the other sodium channels. So we'll start this. We've already started site initiation, and we look forward to dosing that in the middle of the year.

So any thoughts on the initial dose and what you are looking for?

We know exactly the initial dose. And so we've gone for a dose that looks like it should be the lowest therapeutic effect, and we have 3 dose cohorts, and we'll share details of that in the future.

Okay. And what could be the initial measurement you'll be looking for? That will be just pain score or...

It will be pain -- I mean pain scores are the most important. These patients' lives are dominated by their pain. And would we use this in acute pain?

No.

Because in acute pain, there's a whole variety of other things that you could do. This is for people with intractable pain whose days and nights are dominated by that pain and who really don't have any other alternative and would love to stop taking some of the opiates or the channel blockers or the baclofen or all the other things that they take to try and control this pain.

So is that 12 weeks measurement?

We'll be measuring the response over the first 12 weeks, but we intend to follow this out hopefully for a year to show a continued benefit because this isn't for a short-term benefit. This is for long-term benefit to the patient.

And given the noise of the pain score measurement, could that be different from the traditional Phase I study? Were you thinking about one cohort as a placebo so that you sort of manage the noise...

Each cohort will include a placebo and then that will generate in effect, a placebo cohort. I often get asked about the placebo in this. These are patients with dreadful intractable pain. This is a medicine that should switch off the pain signaling and should, if it is a valuable medicine, have a dramatic effect. In addition, the placebo effect is maximized when you're taking the tablet every day. You're reminded that you're taking an active medicine. This is a case where the patients will be dosed and then if you take the 12-week point, for example, it's 12 weeks since they had the intervention. And so the memory of what they had may be less placebo-like than a daily tablet.

I see. Okay. And then I think more of the scientifically, I think -- do you think it makes sense to try to target both NaV1.7 and NaV1.8 and giving you have easy capability of doing both, yes?

Yes. And one day, that might be an interesting experiment to do. The advantage of -- one of the real advantage of zinc fingers is how small they are. We can -- we could multiplex 3 zinc fingers into a single AAV. But I think it's important to start with Nav 1.7 and see the effect and then decide what needs to be done after that. And even today, one of the investors who was speaking to me was asking -- was remarking this is the initial indication, but there are so many other things that you could expand as to -- trigeminal neuralgia is one obvious one. So we're very excited to see the result of this first patient dosed.

Maybe quickly go back to the SFN study. What kind of like baseline medication you will be -- like you will allow a patient to take?

I think we have to accept that these patients need their medicines because their lives are so hard and miserable. So this will be on top of their standard of care, and there will be rules about what that can be. And we will also be monitoring rescue medicines because we can't force the patient to be with pain when that's unnecessary.

Will you normalize the rescue meds and also the baseline in the therapy? Do you try to...

We will be very thoughtful in the baseline medicines that are allowed to try and make the signal as effective as -- as clear as possible. I just want to say again, this is a once-and-done medicine that will give patients long-term benefit. For that to be a useful medicine, it has to be an effective and safe medicine. And so we believe that we will see a clear signal in this. If you and I are trying to sift between the placebo, this probably isn't an effective medicine.

Good. Well, we are on time. Thank you very much.

My pleasure.