Good afternoon, everyone. My name is Gena Wang. I'm senior biotech analyst at Barclays. Welcome to Barclays Global Healthcare Conference. It is my great pleasure to introduce our next presenting company, Sangamo Therapeutics. With us, we have Sandy Macrae, our Chief Executive Officer. Sandy, why now you give a brief intro, and then we will dive into the questions.
Thank you, Gena, and thank you to everyone. It's always a pleasure to come to Miami and the Barclays Conference and to see you again, Gena. Sangamo is a fascinating company that's executing and delivering on its promise. We have three late-phase assets. Hemophilia with Pfizer, where they've guided that they will file a BLA in the second half of next year. Fabry, where we've shown some great data that I'm sure you want to talk about, and we will hope to move into phase 3 at the end of this year. Sickle cell, where we announced at our last quarterly call that we are looking for a partner for it because there's only so much a company like our size can do.
In addition, we have our Treg portfolio, where we're the only Treg company of 15 that are in the clinic, and we've dosed two and about to dose a third patient in renal transplant with projects in MS and inflammatory bowel disease behind that. The bit that is truly the core of Sangamo is our zinc finger platform, and particularly the repressors and enhancers avoiding the double-stranded break, where we have a wholly owned CNS portfolio that we're really excited to move into the clinic, with INDs in 2024 and 2025 and hopefully making a transformational difference to patients with important disease.
That's good. Maybe I will start with, you know, Fabry disease. Thank you. You do have, you know, the world data update, and I would say like some investors perceive a little bit mixed kidney biopsy. I do know.
Oh, I would disagree with that completely, Gena.
We can discuss, you know, because I think a bit. You know, there are only two patient data. One have a reduction, but the other did not. Maybe we can ask, you know, discuss about what and why would be certain variability, what patient baseline characteristics contribute to this, you know, variability there.
Absolutely delighted to because there was such excitement around this data when we showed it at the WORLDSymposium. Excitement from other companies, from patients, from the investigators who see this as a really unique package of everything from biopsy data, to biomarkers, to physiology, to patient benefit. I think when you put all of that together, there's very compelling data. We decided not to biopsy patients until we got to the chosen dose for phase 3 and only to biopsy patients that were naive or pseudo-naive. Pseudo-naive is six months or more of no ERT. The first patient is a very, patient nine, as we call them, is a very conventional patient.
Started with a very high lyso-Gb3, had a dramatic reduction in lyso-Gb3 and had us a very significant reduction in Gb3 in the kidney. Just as an aside, Gb3 in the kidney we measure using the BLISS process. It's done by three oncologists or two measure it and one adjudicates. It's a very standard process that a lot of the other companies have used, and it's using the histologist that everyone uses in the field. Importantly, we also measured podocyte loss in the urine in these patients. With patient one, there was also a dramatic reduction in podocytes in the urine. What happens in Fabry disease is you get podocytopathy. Podocytes are the little thing.
Podocytes mean feet. They're the little cells that attach around the Bowman's capsule. They're terminally differentiated. When they die, they fall off, they go into the urine. That's how you get proteinuria. That's how you get renal failure. The sign that we were preserving them and they weren't falling off is a real sign of a preservation of renal function. Patient eight, the second patient, showed preservation of Gb3. There was no difference. It's an unusual patient. This is a naive patient that already came in with a very low lyso-Gb3. Right from the start, there's something unusual about that patient. We showed a somewhat of a decrease in the lyso-Gb3. This is a complicated patient. He's got an unusual mutation.
They've got renal disease due to hypertension, diabetes. They've got ITP. Coming in with such a low lyso-Gb3, they would simply be excluded from a phase 3 study. Normally in patients with Fabry, you have to have a lyso-Gb3 greater than 50. That's how you diagnose it. In this early study, we took anyone that was diagnosed as Fabry, so you could be diagnosed on your DNA rather than on your biomarkers. I would have loved them to have gone down as well, but we and others are not concerned by this because we know the patient population will take into phase 3, and we're delighted by the podocyte response because I think that's a really good marker of physiology.
I have a few questions here. First is regarding the baseline. I, you know, do agree this patient seems very low baseline, a lot of other conditions there.
Mm-hmm.
When we also look across, you know, the other data points, and I can see the AVROBIO, they do have a two patient also baseline actually pretty low. You know, when we look at their numbers like 3.55 and a 4.03 at the baseline, and data still show like 80, 87%-100% reduction.
I'm not talking about their baseline. Are you talking baseline in kidney or baseline of lyso-Gb3?
I think it was the kidney.
I think you're talking about the Gb3 in the kidney.
That was the kidney.
We're going to exclude the lyso-Gb3 in the plasma.
Mm-hmm.
If you look at all the data from AVROBIO or for 4DMT.
Mm-hmm.
Patients with low lyso-Gb3 it none of them show a reduction. It's patients with high lyso-Gb3 in the plasma that they show a reduction.
Mm-hmm.
AVROBIO dosed four patients and really only showed data from two, I believe, in the biopsy. There's a complicated story there with AVROBIO that we never saw all the data. 4DMT had two patients with a high lyso-Gb3 that dropped, and the one with a low one didn't change. I think we're all learning from this. If you go to the Fabrazyme data or any of the marketed products, and if you ask the pathologists who look at Gb3 when they're asked to do so in clinical trials, all of them say that there's a range of responses. We're not anchoring this on the incoming level of Gb3 in the kidney. We're saying there's a range of responses. Fabrazyme have patients that don't change.
There's a spectrum and there's a paper that I'm sure you've looked up that shows the spectrum of responses. When we ask the people that treat these patients, they feel that what's more exciting is the range of responses that we've seen across all of those things. The patient benefit, the biopsy in the patient with a high lyso-Gb3, the podocyte response and the SF-36.
Okay. That may be, you know, leading to the question for phase III, and you just say, like, try to exclude the patient that was the low baseline. Do you think, you know, a podocyte response shows very good, but what could be the approvable endpoint? I know you still have to discuss with the FDA.
We have to discuss. As everyone knows, there's been a journey that we've all come along with the agency about what's approvable.
Mm-hmm.
The original guidance some years ago was if you could show a reduction in Gb3 in the kidney, that would get you accelerated approval. It was one of the reasons that everyone came to Fabry because they could see a tractable path forward. AVROBIO went to speak to them and came back with the response allegedly that the agency said they couldn't do a cardiovascular endpoint, and they were setting them a much more difficult task. AVROBIO had other problems 'cause they, their cells didn't engraft reliably, and it was cell therapy. I feel that's quite a different one. 4DMT, when they declared their clinical hold, said that the agency had given them alignment on a cardiac endpoint. Now, I don't know what alignment means, 'cause to me you only get agreement or not with the agency.
Again, you would have to see the correspondence. We went to see the agency last year when we only had four patients' data and a really good conversation with them. It's clear they're wanting to help people register for Fabry. They talked about demonstrating patient benefit and talking about finding good ways to do it. We feel that there is a path forward, and we're gonna go and see the agency. I think it's in about a couple of months. The reason for that timing is by then we'll have a year's worth of data at the highest dose. Now we're putting together a package, and we'll see how compelling whether it needs to have that length of time or whether we just need to get going and speak to them.
Peter Marks, at the same time as we presented the data at the conference at the WORLDSymposium, talked very forcibly about his passion for this and that the agency is going to try and find ways for companies like us, I think, to get registration as quickly as possible and his openness to biomarkers as a way forward. We're now the only company in Fabry disease. The 4DMT's on a clinical hold. Freeline is reducing their force, selling off their manufacturing. AVROBIO has stopped. Amicus has stopped. Sangamo is now best in class, first in class, almost by definition. I think the agency will embrace that and help us take a way forward.
Mm-hmm.
What will the registration trial look like? I'll tell you once I've got agreement from the agency. It will involve biopsy. It will involve patients that are naive and are pseudo-naive, and it will involve patients that are on ERT. The details of it would be unfair of me to tell you now until we get agreement with the agency.
Mm-hmm. That's very helpful. I think that there's another question is about whether you will need active control arm for the phase 3.
that's an important question because.
Mm-hmm.
That changes the complexity of the trial.
Yeah.
We need to go and.
Mm-hmm.
Argue our case with the agency for us to understand that.
Mm-hmm. Okay. Then, do you schedule meeting with FDA after one year data? That will be second quarter?
We're hoping to do it next quarter.
Okay.
We're hoping to.
Second quarter.
Yes.
Right. Yeah.
'Cause our intention, and my team are planning for success, our intention is to initiate the trial at the end of the year and dose the first patient in the first part of next year.
Mm-hmm. Okay.
Patients are waiting, Gena.
Mm-hmm.
The patients love this. If you speak to the patients on our trial, and we've now dosed 20, I think is the formal number. They feel better. Even the ones in ERT say they feel better. Both they tell us they feel better and in their SF-36, I think that's the most interesting result in the trial. It goes up 19.5 points, whereas 3-5 is a significant effect.
Mm-hmm.
That really is... I mean, it's what we're all here for, isn't it? It's the patient feeling better.
Okay, that's very helpful. Maybe quickly on the market opportunity. You know, can you remind us the Fabry patient population, and also was your AAV, if I recall correctly, AAV2/6?
We're AAV6.
Six, yeah.
AAV26, depends how you name it.
Yeah. Yeah. Yeah.
Um-
like, what is the existing neutralizing antibody that could be.
In general, in our.
Mm-hmm.
We have the advantage against the others. We've now dosed, it must be nearly 150 people.
Mm-hmm.
With AAV6 between the MPS trials, the hemophilia, and now this. It varies somewhat between state to state, to be honest, but it's about 30%.
Mm-hmm.
That's us making sure we have a safety, a security margin between the patients with the highest antibodies. There is a subgroup of that 30% that have got very significant antibodies. I can imagine with time, we will explore reducing the titer that we exclude. It's the same for all the other AAVs. They're all about 30%.
Mm-hmm.
Now, the advantage of AAV6 is its safety profile. Some of our competitors came up with completely novel capsids, and they ran into immunogenicity, hemolytic uremic syndrome, myocarditis. I think we have a real tolerability advantage.
Okay, very good. kind of thinking the biomarker data giving the full approval and which also supporting the biomarker is valid because you have a full approval. Would that lead to, like, more likely you will have a biomarker as endpoint?
I'm going to go to the agency.
Mm.
Talk about the whole package. I'm gonna talk about how well-tolerated it is. No use of prophylactic steroids. I'm gonna talk about how we have complete alignment of alpha-Gal A, lyso-Gb3. I'm gonna talk about the biopsy and why we focus on this one patient. I will have other biopsy data as the year progresses. I'm gonna talk about how the patient benefit. I'm gonna talk about how the patients are coming to us. We have a queue of patients to complete this phase 1 to study. I'll have a good, sensible conversation, I am certain, with the FDA about how we can get this registered soon.
Mm.
Then also registered for as many people as possible. Because in a phase 3 study, the two things don't always align. There's a desire to register it quickly, there's also a need to expand the label. We've dosed the first-ever woman for Fabry disease, she's doing well. We will expand it into patients with cardiac disease, with renal disease, that will help inform the design of the study. When we start the phase 3, we will continue to observe the patients in the phase 1, 2. We'll have a cohort of 30 patients, 20 of whom will be on the target dose that will be providing long-term data. Because one of the questions you've asked me before is, do we see continuation of effect? The answer is yes.
Out to 26 months, I think, for the first patient, there clearly is continuation of effect.
Okay, very helpful. Any update regarding the data? You know, will we see more biopsy data later this year?
We really don't want to dribble data out one patient at a time.
Okay.
We will show the next bolus of data.
Mm.
At the appropriate time. We'll tell you when we're ready to go to phase three. We'll tell you when.
Mm-hmm.
You'll hear 'cause we'll register on ClinicalTrials.gov.
Okay.
That may be the next thing to inform.
Okay. Basically after feedback with FDA, then you will share the-
I.
Data for longer.
You'll hear from us in the next couple of months before we speak to the agency.
Okay. Okay, that's fair. Maybe also remind us the reason to choose 5-E13.
5-E13 as a dose.
Yes.
With that. If you look at the naive, pseudo-naive patients, the response at 5-E13 is significantly more than at 3-E13. Than at 1-E13 or 0.5e13.
Mm-hmm. Okay, good. We switch gear. I know we have quite a few other we can discuss. Maybe quickly on hemophilia A. I know it's the partner programs with Pfizer. you know, so far and maybe the latest thoughts giving. We will see how BioMarin's Roctavian will get approval and the market opportunity.
I wish Roctavian all success.
Mm.
They've worked hard at this. They've kept driving forward with the agency. It'll inform so many of the rest of the gene therapy approvals. All I can tell you is Pfizer are signaling very loudly that hemophilia is important for them. They are guiding that they will show the results of the phase 3 in the first half of next year, and that they will file the BL in the second half of next year. Once they do that, there's a series of milestones come to Sangamo. There's $240 million between then and launch in the variety of different markets. There's 14%-20% royalties on what could be a very important drug. This is important. Hemophilia patients love the idea that they can step away from factor and have a life that's under their control.
Mm.
really, I think in the community, we need to start talking more positively about genomic medicines. hemophilia, Fabry, I would hope, where now seven patients are off of ERT or the sickle cell, where patients stop having VOCs. We're making fundamental differences. This isn't a product line extension. This is a new way of thinking about treatment for these dreadful diseases.
Great. I think on the other hand, when we talk to the doctors, particularly hemophilia doctors, they seems more reserved and concerned about the unknown, say, long-term safety. So maybe, you know, like, what is your market feedback, you know,
Come with me and talk to the patients. Come with me and talk to the patients and talk to the patients that have to carry syringes and factor in the fridge and hear about how their life changes. I think the doctors are right to ask for long-term data and to understand how long the promise is. They're right that we, the companies, show them evidence of safety, and they will take time to adopt it.
Mm-hmm.
I think that this is going to be embraced.
Mm.
The patients tell us because we talk to them, five to seven years worth of benefit, it makes the whole equation work for them. Roctavian looks like it'll give five, maybe more years. I can't tell you what we'll do because we haven't seen the phase three data. I really do think the patient promise is there, and I hope that doctors listen to their patients. I'm a doctor, I hope they listen to their patients, and I hope they embrace this important treatment.
Mm-hmm. Maybe one quick question. How would the Sangamo's program or Pfizer program differentiate from BioMarin's program?
Let's wait and see the phase 3 results. 'Cause until we see them, I'm just promising things that I haven't seen.
Okay, that's fair.
one of the differences-
Mm-hmm.
-is it's Pfizer.
Mm.
We all know how effective Pfizer are at negotiating with payers and launching drugs successfully. If Pfizer believe in something, I believe in them and their success.
Okay, good. We have a few more minutes. We do want to touch on a few more other programs. sickle cell, maybe quickly, you know, you discuss with the FDA on the phase 3, but then you decided this will be more focusing for the partner opportunity.
Sangamo, I mean, everyone's aware of our financial situation. We're being extremely careful with our spend.
Mm-hmm.
We are making strategic decisions on what we take forward, listening to investors, listening to advice. There's only so many phase 3 programs that a company our size can do.
Mm-hmm.
We inherited this as a surprise Christmas present from Sanofi. The team did a fantastic job in transferring the IND, which is no major task. It's six months of work to transfer an IND and drive forward with the trial. The patient files that we showed with the new process looks identical to CRISPR Vertex. They're not having VOCs. They've got the same amount of fetal hemoglobin. It's fantastic. We cannot afford to take this forward, and we would rather put our money on other things. We have a process that we've initiated to find a partner for it, because ironically, we have the letter from the agency that says exactly what the clinical trial should look like. It says how many patients. What data we need to have to move forward. It says agreement on the manufacturing process.
We have initiated a manufacturing, update which allows us to put everything in a box and reduce the cost, increase the reliability of manufacturing. This is a phase 3 asset in a box ready to go for someone, and I really hope we can get this forward. 30,000 patients with sickle cell will be waiting for this, and there is no way that any one company will solve all of this.
Good. Quickly on Treg, you know, the initial data expectation, do you think? A few questions.
We've dosed. As you know, we acquired a Treg company in 2018. We have dosed two patients with HLA-A2 mismatched renal transplant. The third is manufactured, is about to be dosed. That's the first cohort. Treg. We're the only company of 15 Treg companies, we're the only one that's in the clinic. We're the only one with our own manufacturing, the only one that has an editing capability, the only one that knows how to do INDs. The first time you go in with the Tregs, there was. The agencies were saying, "Show us it's safe, first and foremost." With the two patients we've dosed, I think we've addressed that.
Now we need to get through the various dose levels to get to the maximum dose and give as many cells back to patients. I can't wait to sit up here and show you the results from that trial. We need to make sure that we're not dribbling out one patient or one patient here. We hope by the end of the year, beginning of next year, to have that data. You know, it's so exciting because this unlocks TREGs as a treatment for autoimmune disease. We have the CARs already built and in testing for multiple sclerosis with MOG and inflammatory bowel disease with IL-23R. A lot of people are interested in our TREG program. They say, though, you know, it's...
How do we invest in Tregs and when we just have to invest in the whole of Sangamo? We need to find a way to address that because there is so much excitement in the potential for Tregs.
You do have tons of the partner programs. Maybe, you know, any progress from the partner programs, TREG is the one you wanted to move, right?
I can tell you that all of our partner programs move forward.
Mm-hmm.
They're delighted with our science. I can also tell you that our partners are going through. All of them are going through their strategic reviews. Novartis has changed the head of NIBR. Biogen has changed their CEO. We're always interested to watch what happens with those programs. It's their strategy. It's their decision to take forward. I'm very clear, when we partner, we partner and get the upfront. When we get the up-upfront, it funds the company. Since I've taken over Sangamo, we've raised $1.6 billion, of which $800 million is from upfront. When you take that, you lose decision rights because it's the other companies. We make sure, with very close alignment, that they're progressing those.
Those assets are moving forward, and they're increasing in value and increasing in importance.
Very good. Quickly, I know we are running out of time. Quickly on the in-house manufacturing. Maybe a little bit highlight on peak capacity and how you decide, you know, with the CDMO versus in-house.
The advantage of in-house manufacturing is that they're right beside the research people, right beside process development, and they can talk over lunch and make sure that the whole thing works well. We have GMP manufacturing for AAV and cell therapy in Brisbane, California, and cell therapy in Valbonne, France. For the early projects, it seems wise to use them as much as possible. We are very clear that, you know, once we get into late phase development or commercialization, we will work through CDMOs, and we have great relationships with CDMOs.
Lastly, SVB impact. I know you mentioned.
SVB. You know, it's very easy to criticize SVB. Many startups and biotechs depended on them, and they were our banker of choice. We moved 90% of our money out of them two or three years ago. We guided on Friday. We had 34 left. We guided today, I believe, that we've removed it all. We have removed all our money from SVB. It's safely with one of the large American banks.
Okay, great. Well, thank you very much, Sandy.
Thank you, Gena.
Thank you, everyone.