Alexander Macrae

Thank you, Louise, and good afternoon to everyone joining the call today. This has been such an exciting and important quarter for Sangamo. At our last earnings call, we shared compelling preclinical data, demonstrating the potential of our neurology epigenetic regulators, AAV capsid delivery platform, and next-generation genome engineering platform.
Importantly, we also outlined our resolute focus on raising additional capital in order to progress these compelling assets into the clinic and supports patients in need. To that end, this morning, we were thrilled to announce our first neurology epigenetic regulator and delivery capsid license agreement. This comes close on the heels of the highly compelling Phase 3 AFFINE data for the hemophilia A gene therapy we are co-developing with Pfizer.
Both announcements demonstrate external interest in and validation of the potential of our science. And both could meaningfully extend our cash runway as we continue to advance our wholly owned neurology epigenetic regulation pipeline.
Getting into the details of our STAC-BBB capsid deal, this morning we announced a license agreement with Genentech to develop novel, intravenously administered genomic medicines for neurodegenerative disease. We have granted Genentech an exclusive license to our highly potent zinc finger oppressors that are targeted to tau, a critical gene involved in Alzheimer's disease and other tauopathies, as well as an additional undisclosed second neurology target.
For these same targets, we've also granted Genentech an exclusive license to our industry-leading neurotropic delivery capsid, STAC-BBB, which has demonstrated potent blood-brain barrier penetration and brain transduction in non-human primates.
As we have shared before, we strongly believe that our powerful combination of proprietary genome targeting cargo paired with our neurotropic delivery capsid platform is critical to the successful development of neurology-focused genomic medicines. We believe this agreement with Genentech, a leader in the biotechnology and neurology space, reinforces this potent combination and underscores how Sangamo is able to provide both.
We are delighted that Genentech chose our zinc finger and capsid delivery technologies to address their neurology needs. We expect to receive from Genentech $50 million in near-term upfront license fees and milestone payments, which we anticipate will extend our cash runway into early 2025 and are eligible to earn up to $1.9 billion in development and commercial milestone payments, as well as tiered royalties or net sales of such products under the agreement.
Our agreement with Genentech is significant as we believe it paves the way for others in the future. We anticipate this agreement could be the first of multiple capsid collaborations as we have ongoing discussions with other interested parties alongside our Fabry partnership discussions.
Generating additional funding continues to be our top priority as we work to position Sangamo for long-term success and value creation and are hopeful to have news of additional transactions in the second half of this year.
I would now like to hand over to Nathalie, our Head of Development, who will share details on the positive top-line Phase 3 AFFINE trial results and take us through other pipeline updates. Nathalie?

Nathalie Dubois- Stringfellow

Thank you, Sandy. As Sandy outlined, we were thrilled to recently share positive top-line results from the Phase 3 AFFINE trial of giroctocogene fitelparvovec and investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A.
Hopefully, we had an opportunity to look at the results. But to summarize the key point, the AFINE trial achieved its primary objective of non-inferiority as well as superiority of total annualized bleeding rate, or ABR, compared with routine Factor VIII replacement prophylaxis treatment following a single dose of giroctocogene fitelparvovec demonstrated a statistically significant reduction in mean total ABR compared to the pre-infusion period.
Key secondary endpoint were met and also demonstrated superiority compared to prophylaxis with 84% of participants maintaining Factor VIII activity greater than 5% at 15 months post-infusion. And the majority of having Factor VIII activity greater than or equal to 15%.
Furthermore, the mean-treated ABR showed a 98.3% reduction post-infusion. Importantly, the product candidate was generally well tolerated. These impressive results further validate the potential of our genomic technologies and take us one step closer towards what could become Sangamo's first medicine commercially available to patients.
We greatly appreciate Pfizer's strong leadership of this important program. And we're therefore pleased to see these updates prominently profile in their second-quarter earnings update last week. Pfizer reiterated that they plan to review this data with regulatory authorities in the coming months, which would take us a further step closer to unlocking a substantial first tranche of the anticipated milestone payments.
As a reminder, we are eligible to earn up to $220 million in milestone payment from Pfizer upon the achievement of certain regulatory and commercial milestones and 14% to 20% royalty on potential sales for this program if approved and commercialized.
Positively impacting the lives of patients is our ultimate goal. So selecting a partner with strong commercialization infrastructure and experience, as well as a broader franchise in this area, was an essential criterion when selecting a partner for this program some years ago. We look forward to hearing Pfizer's progress on this program in the coming months.
This quarter, we also continue to advance our Fabry disease program, and I wanted to take a moment to share how the Fabry clinical data continues to evolve and demonstrate real patient benefits. As outlined previously, dosing is complete in the Phase 1/2 STAAR study of isaralgagene civaparvovec, an investigational gene therapy for the treatment of Fabry disease with a total of 33 patient dosed.
Since our last update, we are pleased that three additional patients have been able to stop enzyme replacement therapy or ERT, resulting in a total of 17 patients withdrawn from ERT to date. All 17 patients remain off ERT as of today. The one remaining patient dosed will begin the study on ERT as plans in place to withdraw ERT treatment at the appropriate time.
To reiterate, 17 patients no longer have to undergo long ERT infusion session every second week. This is a life-changing development for those patients.
With the longest treated patient now to nearly four years and with 10 patients having at least two years of follow-up, we continue to amass important clinical data, including durability from this study. These data continue to look highly encouraging with patients achieving and maintaining physiological or supraphysiological level of plasma alpha-gal-A enzyme activity.
What particularly pleases me is that we're seeing evidence of improvement in kidney function. In contrast to the progressive decline in kidney functions in untreated Fabry patient and even those on ART, in the 18 patients treated for more than one year, we are seeing a statistically significant rise in both mean and median EGFR levels in male and female patients, those with isaralgagene civaparvovec. This reflects an important improvement in kidney function. We look forward to sharing a detailed data update in the coming months.
In June, we also held a productive meeting with the European Medicine Agency or EMA on a proposed pathway to potential approval in Europe. In particular, we were impressed to be joined in that discussion with nine members of the US Food and Drug Administration. Finally, our engagement with potential Fabry collaboration partners continues with multiple discussions ongoing.
This advances allows us to focus on our mission as a genomic medicine company to treat debilitating neurological disorders. We believe our ability to combine proprietary zinc finger epigenetic regulation payloads with exciting new industry-leading capsid delivery technology could unlock significant potential for the treatment of devastating neurological diseases, indication for which delivery to the central nervous system has historically proved challenging.
This quarter, we continue to advance IND-enabling activities for our zinc finger repressor in chronic neuropathic pain, Nav1.7, as well as CTA-enabling activity for our program to treat prion disease, which leverages our novel STAC-BBB capsid. And we also shared exciting development in our next-generation genomic engineering efforts to integrate larger sequences of DNA into the genome, an approach that could offer the potential with a single medicine patient who have unique mutation in the same gene.
I will now hand it back to Sandy for closing remarks.

Alexander Macrae

Thank you, Nathalie. In closing, we're delighted with the important progress made this quarter, which can be summarized in three areas. First, we are proud that our epigenetic regulation and capsid delivery capabilities are being recognized by leaders in the field. We expect that the near-term payments to be received from Genentech will extend our cash runway into the first quarter of 2025, reinforcing the potential of our science and providing us with needed near-term financial resources. We believe this could be the first of multiple capsid collaborations to come with other partners, which we hope will create a stream of future non-dilutive funding opportunities.
Second, we are excited to have achieved important advances in our legacy gene therapy programs, which provide a foundation for our core neurology business. The positive top-line data from the Phase 3 AFFINE trial take us one step closer toward what could be Sangamo's first medicine commercially available to patients and the resulting important potential milestones and royalties that would follow. The compelling clinical data emerging Fabry disease program, coupled with the encouraging potential regulatory pathway, further underscores the importance of our science, and we anticipate we'll further fund the company.
Third, this stream of non-deluted funding opportunities provides the foundation to build our neurology epigenetic regulation pipeline and capsid deliver platform led by our chronic neuropathic pain and prion disease programs, both of which continue to advance towards potential IND and CTA submissions.
We will continue to build our progress in the second half of 2024 and look forward to continuing to achieve key milestones to bring our promising technology to patients in need.
Operator, please open the line for questions. Thank you.

Question and Answer Session

Operator

At this time, we will conduct a question-and-answer session. (Operator Instructions)
Nicole Germino, Truist Securities.

Nicole Germino

Great. Thanks so much for taking my question and congrats on all the progress. You've noted that STAC-BBB is manufacturer of scale. Can you elaborate on this a bit more and what this means potentially from a cost of goods perspective compared to the standard process?

Alexander Macrae

Thank you for your question. Amy, can you help with that, please?

Amy Pooler

Yeah, sure. I'm happy to comment on that. Once the discovery of STAC-BBB was made, one of the first things that we did was look into the manufacturability of the capsid, knowing that that's an important consideration when scaling up in order to be able to make enough of the capsid to treat these devastating neurological diseases we mentioned earlier.
What we found that, by and large, STAC-BBB capsid behaves very similarly to its parent capsid. So we believe that all of the expertise that we've developed for our previous programs in manufacturing AAV can be leveraged now for STAC-BBB.

Alexander Macrae

Thanks, Amy. And it's one of the gating factors in choosing this capsid to move ahead.

Nicole Germino

Thank you.

Operator

Gena Wang, Barclays.

Gena Wang

Thank you for taking my questions. I wanted to congrats on the great deal with Genentech. So maybe wanted to ask regarding the partnership, they're open for additional indication beyond the two indications that already decided regarding this deal.
And then second regarding the Fabry disease, now you have a more compelling clinical data and also strengthened cash position. What is your latest thoughts on the Fabry program path forward, whether as a standalone asset or you want to still continue looking for the partner to divest this asset?

Alexander Macrae

So you have to excuse us, you were very quiet. Can I make sure that we understood the questions? I think the first one was about STAC-BBB and was it available for other indications and would we be doing partnering for other indications? Did I understand that correctly?

Gena Wang

That's correct. Sorry. Can you hear me better now?

Alexander Macrae

Yes, that's much better. Thank you. So the license we have with or the partnership we have with Genentech is for they have named their first indication as TAU, which clearly applies to Alzheimer's and the various tauopathies; and a second, undescribed target. All other targets are unclaimed at the moment.
Of course, we at Sangamo want to take forward prion and we have a range of, I think, there's eight in our current pipeline on the website that we would consider, depending on resources, taking forward. We're really lucky that we've been inundated by other companies looking for opportunities to access the capsid.
And we're being very careful to hear the ones that they're interested in and make sure that that fits with the ones that we want to take forward. So it really does speak to the importance of this capsid and the many neurological conditions that hopefully will be addressed with various cargos in this capsid.
And then the second question I think you asked was about Fabry. Nathalie, can you update us on where we are with the Fabry study, please?

Nathalie Dubois- Stringfellow

So we have very encouraging data. But if I understand your question, you're wondering if we are still wanting to partner?

Gena Wang

That's correct.

Nathalie Dubois- Stringfellow

Yes. So we have very encouraging data and really a remarkable path forward. We've agreed with the agency. But it doesn't make sense for us to set up a commercial infrastructure around a single product.
So we believe a company with the appropriate commercialization infrastructure would be best placed to take this medicine more quickly and effectively with patients.

Alexander Macrae

You know, what's really interesting is the longer we follow the Fabry data, the more interesting it becomes. We have patients out at four years. We have several out at two years. We have 17 patients now that have come off of ERT and none of them show any sign of going back on.
And then the more recent data that we got that we describe in this where we show an improvement in the EGFR, so this isn't a biopsy. This isn't a biomarker. This is what's important to patients and what determines the fate of patients and in some case literally their fate. And the EGFR drops year on year in patients with Fabry disease.
ERT slows that somewhat, but we've been told no one has ever seen an EGFR that actually statistically improves, both the mean and the median improves. And it really speaks to the clinical utility as a physician, the clinical utility of this medicine.
So we have several companies that we're talking to now. They too have got very excited by the CGFR data. We see this as an important medicine. The team's driving goal is to get this to patients. However it takes to do it, we will make sure that this is a medicine because it is making such a difference to patients with Fabry disease.

Operator

Yanan Zhu, Wells Fargo.

Yanan Zhu

Great. Thanks for taking our questions and congrats on the progress. So maybe first a couple of questions for the Genentech collaboration, specifically on the technology front. I was wondering, are there new engineering features in the zinc finger repressor that Genentech licensed? Is the repressor similar or different with any of the prior and/or current zinc finger repressor product candidates that have been worked on?
And secondarily, I was wondering how deep of a repression can zinc finger repressors achieve? And how much repression is necessary for achieving therapeutic benefit in suppressing tau?

Alexander Macrae

Thank you. Those are all great questions. And Amy, I'm sure you'll love to answer them.

Amy Pooler

Yeah, absolutely. Thank you for the question. The zinc finger repressor technology is something that Sangamo has been working on for some time, and we are really confident in both the potency and the specificity of the platform. The zinc finger, especially for tau, is really a beautiful example of that zinc finger technology.
Now, the thing that was missing in the past for the tau program really was a way to deliver. We know that these tauopathies, especially in Alzheimer's disease, affect the whole brain. And with a direct injection approach or an intrathecal CSF approach, we really weren't able to achieve that widespread brain distribution that we think would be critical for treating the disease.
The important thing is to pair that potent and specific tau zinc finger repressor with the STAC-BBB capsid in order to achieve that. As we showed in ASGCT earlier this quarter and also in our corporate deck, we have really outstanding distribution of the STAC-BBB capsid throughout key brain regions that are involved in Alzheimer's disease. So we're really excited about that.

Yanan Zhu

So in terms of --

Alexander Macrae

And I think the other piece that we're delighted about in this is Genentech. Genentech and Casper, the Head of Neuroscience at Genentech, has always been a great fan of zinc finger as a way to control gene expression. They have a love and a passion for Alzheimer's. We feel in their hands it will get to patients as quickly as possible. So this, from a Sangamo point of view, is getting the right deal with the right partner. And for us, it validates both our cargo, the zinc finger repressor, and our capsid. We're delighted to partner with Genentech in this.

Amy Pooler

And then to follow up on the second part of the question about the potency of the repression, we see greater than 90% repression on a cell-by-cell basis in neurons, which are the key cell type that are affected in Alzheimer's disease.
So that demonstrates this potency. We see that both in vitro in neurons that we can grow in the dish and also in vivo in the animal studies that we've completed.

Alexander Macrae

And, Amy, what's necessary?

Amy Pooler

Now, that's the million dollar question. What we see with the STAC-BBB repression, mediated repression that we've demonstrated in non-human primates, we believe is at levels that is necessary. Again, on the single cell basis, that's over 90% in those neurons. So really excited about being able to move this program into development and get into patients.

Yanan Zhu

That's very, very helpful. If I may ask two additional questions. One on STAC-BBB, it sounds like this capsid really has a lot of very intriguing features, not only for broad neuron transduction but also impressive detargeting of the liver. I was wondering, have you undertaken any work to characterize what might be the cell surface target that is targeted by this engineered capsid?
And another question on the Fabry program, I was just wondering, hearing about the improvement in EGFR, could you give us a little bit more color on how many patients do you have long-term EGFR data for? And also what might be the venue for this upcoming data readout? Thank you.

Alexander Macrae

Thank you for your questions. Great questions again. Amy, can you talk a little bit about STAC-BBB?

Amy Pooler

Sure. We presented some data on the possible mechanism of blood-brain barrier crossing of STAC-BBB at the ASGCT conference earlier this year. What we found was a potential mechanism where it's highly conserved protein in both mouse, non-human primate, and human. And of course, the data that we've seen in the non-human primate is really compelling.
But we also understand that the most important thing is the proof of principle in humans. And this is really why we're so excited to be driving forward the STAC-BBB capsid with our prion program. And that will give us the potential to make a difference in the lives of patients that have this fatal disease.

Alexander Macrae

Nathalie, can you talk about the longer-term data that we have with Fabry, please?

Nathalie Dubois- Stringfellow

Yes. So at this point, we have 18 patients at one year where we have followed the EGFR. And we can see that there is the mean and -- both the mean and the median of EGFR is improved when you look at those 18 --

Alexander Macrae

Statistically, significantly.

Nathalie Dubois- Stringfellow

Statistically significantly improving those 18 patients. In this patient, we have both male and female, so we're very excited with this data because we demonstrate for the first time an improvement in EGFR, which really does not happen on ERT.

Alexander Macrae

And if you remember in addition, the patients are coming off their ERT, their SF-36 is positive. They're sweating. Just the general symptomatology of these patients is all positive and the capsid is incredibly well tolerated. So we're very pleased and the patients and the patient support groups are very pleased with the progress of this.

Yanan Zhu

Got it. Thank you. I look forward to seeing the data.

Operator

Maury Raycroft, Jefferies.

Maury Raycroft

Hi. Thanks for taking my question, and I'll add my congrats on the Genentech deal as well. I have a question just on hemophilia A with Pfizer. Since the $70 million milestone payment is tied to the BLA filing, which seems like a lower-risk event for Pfizer, could you potentially accelerate that milestone payment? And for the commercial milestones, would you consider renegotiating earlier payments for those milestones as well?

Alexander Macrae

Thanks for the comment, Maury. We look forward to Pfizer moving this forward into registration and beyond. We were particularly encouraged by the recent Pfizer, the quarterly call, where this was a core part of their pipeline and something that they spoke of and were excited about, particularly as it matches with their hemophilia B acid as well.
We don't give details of when these milestones will be coming. We don't need to draw down these milestones or royalties. Of course, when the results were announced, we had inbound inquiries from royalty companies who were interested in talking about that with us.
But we're so close to the registration that it's a balance between supporting Pfizer and believing in Pfizer and the need for cash now. And so we are blessed to have that choice. With this money that we've brought in from Genentech, it gives us time and it gives us an opportunity to complete other business development deals.
With the Fabry, we have the choice and the results are giving us incoming interest on the clinical benefit. With the capsid and cargo that Amy has created, we can do other capsid and cargo deals. So this has been a great turnaround from Sangamo. This is the beginning. And we are fortunate to have so many assets that we can monetize and choose our own path.

Maury Raycroft

Got it, that makes sense. That's helpful. And maybe one quick follow-up. I'm just wondering if there's more you can say about the STAC-BBB out-licensing process and the extent of diligence from Genentech and whether other parties were involved for tau specifically.

Alexander Macrae

There's a limit to what we can say. We saw this data first about STAC-BBB in November in amongst a whole other library. We saw the data on the single capsid in March and the business development team did a great job of driving it forward. Of course, I wanted it sooner. And they will be smiling at me saying what a great job they have because I'm always asking them to do it sooner.
Why we particularly like Genentech as our partner is they did deep, deep diligence. They turned over every stone. They worked closely with Amy and her team to make sure that they were making the right choice both with the capsid and cargo. We have several other companies that we're talking to and we're very careful to make sure that we know what they want as their intended target, to make sure we can maximize the value that we can get from this capsid.
Amy, it really was significant scientific diligence, wasn't it?

Amy Pooler

Yeah, it was such an exciting process and really such an honor also to go through it with the Genentech team. They're really wonderful, looking at the data together and working in such a collaborative way. So really looking forward to working together.

Maury Raycroft

Great. Okay. Thanks for taking my question.

Operator

(Operator Instructions)
Lisa Walter, RBC.

Lisa Walter

Okay. Great. Thanks for taking our questions. This is Lisa on for Luca. First, on Fabry, it has been about 10 months since a search for a partner has started by my count. Sounds like there have been some fruitful discussions going on with strategic and as well as clinical data progress and progress with FDA and EMA regulators, too. But just wondering if you can add any more color on what is holding a potential strategic back here from partnering with you on Fabry.
And my second question on hemophilia A, just wondering how the conversations with Pfizer are evolving on which regions will be most strategic to file a BLA. In the past, I believe the US, EU, and Japan were flagged. However, we saw yesterday that BioMarin is opting to limit their launch now to only three countries: the US, Italy, and Germany.
So my question is: will a more focused launch be under consideration? Or do you need to go abroad for hemophilia A considering you'll be a second to market? Any colors here would be helpful. Thank you.

Alexander Macrae

So I'll answer the second question first. We can't comment and won't comment on Pfizer's marketing plans. That just is not appropriate and it's also in the contract that Pfizer would be the people who would speak to that.
We noted with interest by BioMarin reducing the number of companies who are intending, you're reducing the investment. It's really hard to relaunch a product and we're pleased that this gives Pfizer an opportunity to make this medicine available. Our data looks great. The efficacy looks good. The tolerability looks good. And in Pfizer's hands, I'm sure it will be an important medicine.
You asked an interesting question about Fabry. We're determined to do the right deal, not a quick deal, do the right deal. And with the money that we brought in from the Genentech deal, we have the time to work with the right partner to take Fabry forward.
What's interesting is as the discussions have continued, is the data has matured. The data has improved. The biopsies are starting to come in in the coming months. The EGFR is statistically significant and the partners are excited. And we look forward to solving this as soon as possible. It's an important medicine and it's important that we get it right.

Operator

I am showing no further questions. I would now like to turn the call back to Louise Wilkie for closing remarks.

Louise Wilkie

Thank you once again for joining us today and for all your questions. As a reminder, you can access our presentation on the Investor Relations section of the Sangamo website. We look forward to keeping you updated on our future developments.

Operator

Thank you for your participation in today's conference. This concludes the program. You may now disconnect.