Sangamo Therapeutics Inc

NASDAQ:SGMO

Earnings Call Analysis

Sangamo's Significant Progress: Fabry Disease and Upcoming Milestones

Sangamo Therapeutics has made notable strides, transitioning from a Phase I/II to a pre-BLA company through regulatory alignment for its Fabry disease treatment, potentially leading to approval three years earlier than previously anticipated. A BLA submission is expected in late 2025. Additionally, partnerships with Pfizer and Genentech could unlock up to $220 million in milestones and provide financial stability. The recent $50 million agreement with Genentech has extended cash runway, allowing for the advancement of ongoing projects. Sangamo aims to submit its first IND for neurology in mid-2025 and is poised for future growth as it tackles serious neurological disorders.

Sangamo Therapeutics' Momentum in Gene Therapy Development

As Sangamo Therapeutics approaches the conclusion of 2024, leadership reflects on a year of significant accomplishments. The company has shifted from a Phase I/II status to a pre-BLA company, especially evidenced in its Fabry disease program, which has received favorable regulatory feedback from the FDA. Importantly, Sangamo has navigated discussions that promise to accelerate the approval process for its lead gene therapy candidate.

Impactful Regulatory Developments

The FDA's acceptance of the eGFR slope data from the Phase I/II STAR study is a defining moment. This pathway marks a three-year reduction in the anticipated approval timeline, allowing Sangamo to aim for a Biologics License Application (BLA) submission in the second half of 2025. The therapeutic requirement now focuses on 52-week data instead of a costly registrational study, which is vital since Fabry disease patients have unaddressed medical needs.

Financial Opportunities from Partnerships

Sangamo's collaboration with Pfizer on hemophilia A stands to unlock significant revenue potential, with the agreement pointing toward up to $220 million in regulatory and commercial milestones over the next two years. Additionally, Pfizer's commitment to presenting critical Phase III data suggests robust internal support for the hemophilia program, which bodes well for Sangamo’s financial stability following any regulatory approvals.

New Agreements Enhancing Future Prospects

The $50 million licensing agreement with Genentech establishes further cash flow for Sangamo while strengthening its platform for collaborations. This agreement reflects growing interest in Sangamo's technology and positions it to attract more partnerships, which are essential for advancing its pipeline and providing non-dilutive funding.

Pipeline Advancements and Future Expectations

Sangamo’s pipeline beyond Fabry disease is vibrant, with plans to conduct a first-ever IND application for its ST-503 program targeting intractable pain expected around mid-2025. The anticipated start of this Phase I/II study could expand Sangamo's therapeutic reach into neuropathic pain treatments, addressing a significant unmet need in patient care.

On the Horizon: Eager Anticipation for Results

Investors should watch closely for upcoming releases of clinical data in 2025 from both the Fabry program and the ST-503 initiative. Positive results could further establish Sangamo’s proceedings as it seeks to maintain its momentum and enhance its appeal to potential investors and collaborators. The distinct prospect of two BLA submissions by next year signals a pivotal moment for the company moving forward.

Staying Focused on Financial Stability

Sangamo remains vigilant regarding its cash runway, with sufficient funding to sustain operations through early 2025. This stability comes at a crucial time, as the company prepares for potential revenue inflow from its Fabry partnership, hemophilia milestones, and further collaborations like those surrounding the STAC-BBB delivery technology.

Patient-Centric Focus Driving Strategic Decisions

A consistent theme throughout the call is the commitment to patient impact. Through discussions at the National Fabry Disease Foundation Patient Conference, it was emphasized that existing therapies, like enzyme replacement therapy (ERT), have significant patient burdens. Sangamo’s innovative solutions aim to address these challenges effectively, potentially redefining treatment paradigms.

Innovation as a Cornerstone for Growth

Sangamo’s advancements in targeted gene therapies—specifically through its novel zinc finger technology and capsid delivery systems—position the company favorably in the burgeoning field of genomic medicine. Its scientific endeavors are aligned with addressing critical health issues and capturing significant market opportunities.

Earnings Call Transcript 2024-Q3

[Operator]

Good afternoon and welcome to the Sangamo Therapeutics Third Quarter 2024 Teleconference Call. Please be advised that today's conference is being recorded.

I would now like to turn the conference over to your speaker today, Louise Wilkie, Vice President of Investor Relations and Corporate Communications. Please go ahead.

[Louise Wilkie, executive]

Thank you. Good afternoon, everyone. Thank you for joining us on the call today. On this call are several members of the Sangamo executive leadership team, including Sandy Macrae, Chief Executive Officer; Nathalie Dubois-Stringfellow, Chief Development Officer; and Prathyusha Duraibabu, Chief Financial Officer.

Slides from our corporate presentation can be found on our website, sangamo.com, under the Presentations page of the Investors and Media section. This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements related to Sangamo's cash runway, plans to obtain additional capital and ability to continue operating as a going concern, the therapeutic and commercial potential of Sangamo's product candidates and technologies, Sangamo's ability to earn and receive payments from its collaboration and license agreements, including the Genentech and Pfizer agreements, Sangamo's expectations regarding new collaborations and license agreements, the anticipated plans and time lines of Sangamo and its collaborators for clinical trials, clinical data presentations and releases, regulatory submissions and regulatory approvals, upcoming catalysts and milestones and other statements that are not historical facts.

Actual results may differ materially from what we discuss today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically in our annual report on Form 10-K for the fiscal year ended December 31, 2023, as supplemented by Sangamo's quarterly report on Form 10-Q for the quarter ending September 30, 2024, and subsequent filings and reports that Sangamo makes from time to time with the SEC. The forward-looking statements stated today are made as of today and we undertake no duty to update such information, except as required by law. Please note that all forward-looking statements about our future plans and expectations are subject to our ability to secure adequate additional funding.

Now I'll turn the call over to our CEO, Sandy Macrae.

[Alexander Macrae, executive]

Thank you, Louise and good afternoon to everyone joining the call today. As we near the end of 2024, I'm extremely proud of the progress we are making this year. We are committed to translating groundbreaking science into medicines that transform the lives of patients and families afflicted with serious neurological diseases.

The updates we will share today demonstrate several meaningful advances towards that goal and show how we believe Sangamo is well positioned for continued progress.

First, Sangamo has transformed from a Phase I/II company to a pre-BLA company as a result of significant regulatory developments in our Fabry disease program. Second, Pfizer continues to engage in discussions with regulatory authorities concerning our hemophilia A program, both of which have the potential to provide a long-term financial foundation for our core neurology pipeline. Third, we signed a neurology epigenetic regulation and capsid delivery license agreement with Genentech and received $50 million in upfront license fees and milestone payments. And finally, we submitted our first ever IND application for a neurology indication. These developments demonstrate that Sangamo is steadily executing upon our strategy, is driving potential medicines towards patients in need and is continuing to advance plans to put the company on a more stable financial footing.

Nathalie will share more context in a moment, but I want to start out by highlighting the significant clinical and regulatory progress made this quarter in our Fabry disease program, following alignment with the FDA on a clear regulatory pathway to accelerated approval. This pathway reduces the time to potential approval by 3 years and avoids the requirement for an additional lengthy and costly registrational study, which is incredibly impactful given the unmet medical need for patients with Fabry disease. We are delighted to have such a clear regulatory pathway that could bring this treatment to patients significantly sooner than originally anticipated and have begun to execute BLA readiness activities ahead of a submission anticipated in the second half of 2025. As you can imagine, this announcement has generated a lot of interest from external stakeholders, including patients who tell us about the remarkable change our treatment has brought to their lives, investors and potential strategic partners.

We continue to engage in ongoing business development discussions as we seek to get this treatment to patients as quickly as possible. Following the recent top line readout from Pfizer for the Phase III AFFINE trial in hemophilia A, we also moved closer to potential regulatory submissions for this program, which has the potential to unlock up to $220 million in regulatory and commercial milestones for Sangamo over the next 2 years. Pfizer will present a detailed Phase III data update at the upcoming American Society for Hematology or ASH Annual Meeting in December. And Pfizer have advised us that they are discussing this data with regulatory authorities, which is very encouraging.

Taken together, the Fabry and hemophilia A programs could provide Sangamo with a solid and long-term financial foundation for our core neurology pipeline. We are thrilled to be in the enviable position of seeing up to 2 potential BLA submissions in 2025 for product candidates developed by Sangamo, each of which leverage the best of our science and capabilities and address significant unmet patient needs and commercial opportunities. This exciting momentum propels our neurology pipeline forward as we work to advance our science and technology for neurological indications.

This quarter, we signed our first neurology epigenetic regulation and capsid delivery license agreement. We have granted Genentech an exclusive license to our highly potent zinc finger repressors that are directed 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 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 nonhuman primates. We have received $50 million in upfront license fees and milestone payments from Genentech, which extended our cash runway to allow us to continue advancing other ongoing business development activities. This agreement has further drawn interest in our science and enhanced our ability to attract new potentially valuable partnerships. We are currently advancing business development discussions with additional potential collaborators seeking to license our novel intravenous capsid, STAC-BBB, and we believe this capsid is a potentially valuable source of additional non-dilutive funding.

This quarter, we also submitted our first ever IND application for a neurology indication. We expect our lead program, ST-503 for intractable pain to advance into the clinic in the middle of 2025, assuming clearance of the IND with the FDA with our expected prion clinical trial authorization submission followed close behind by the end of 2025.

Our cash runway remains unchanged and is sufficient to fund our planned operations into the first quarter of 2025, absent any potential funding from a Fabry partnership, hemophilia A milestone payments from Pfizer or additional STAC-BBB collaboration agreements. Alongside the 2 anticipated BLA submissions next year, we see a viable path to financial stability.

I would now like to hand it over to Nathalie, our Head of Development, who will share additional context and also take us through other pipeline updates. Nathalie?

[Nathalie Dubois-Stringfellow, executive]

Thank you, Sandy. Beginning first with Fabry, we were excited to announce last late month that we have aligned on a clear regulatory pathway to accelerated approval with the FDA for isaralgagene civaparvovec or ST-920, our wholly owned gene therapy candidate for the treatment of Fabry disease. The FDA has confirmed that estimated glomerular filtration rate or eGFR slope data at 52 weeks from all patients in the ongoing Phase I/II STAR study can serve as the primary basis for approval under the accelerated approval pathway.

This pathway avoids the requirement for an additional costly registrational study as we had previously anticipated and importantly, accelerates the estimated time to potential approval by approximately 3 years. Sangamo engaged with the FDA on alternative pathway to potential approval following analysis of clinical data from the Phase I/II STAR study showing encouraging safety and efficacy data. Renal manifestation such as proteinuria or decreased estimated glomerular filtration rate, or eGFR, occur early in life in almost all male and in many female patients with Fabry disease and can lead to end-stage renal disease and early death.

EGFR is assessed in millimeter of cleansed blood per minute per body surface. For context, the average untreated patient has an eGFR slope of minus 5.6. However, in the 18 male and female patients treated with isaralgagene civaparvovec with more than 1 year of follow-up data, we observed a statistically significant positive mean annualized eGFR slope.

Generating a positive eGFR slope is a truly remarkable achievement for Fabry patients, especially since other Fabry therapies according to public data, improve eGFR value compared to untreated Fabry patients, but still show a negative overall eGFR slope. Based on this latest data, the FDA agreed that eGFR slope at 52 weeks can serve as an intermediate clinical endpoint to support a potential accelerated approval. The FDA also advised that eGFR slope at 104 weeks may be assessed to verify clinical benefits.

The complete data set to support the accelerated approval pathway will be available in the first half of next year, unlocking a potential BLA submission in the second half of 2025, 3 years ahead of previous estimates. We are delighted to have a clear regulatory pathway that could bring this treatment to patients in need significantly sooner than originally anticipated. Fabry is a debilitating disease for which there is a serious unmet medical need and this need was clear at the National Fabry Disease Foundation Patient Conference held in October, at which Sangamo was in attendance.

During focus group discussions, Fabry patient elaborated on the challenges associated with current treatment option, including having to switch treatment regimen due to unwanted side effect, insufficient resolution of their symptom and breakthrough pain. Patients also noted the challenges of receiving long infusion every second week, which is logistically problematic and at time can cause them to skip doses. As a reminder, our Phase I/II STAR study has enrolled and dosed 33 patients, representing a broad range of Fabry patients. We have patients who were on ERT at the start of the study as well as patients who were ERT-naive or pseudo-naive. We have male and female patients as well as those with cardiac or renal implication. With the positive annualized eGFR slope observed thus far across these different types of Fabry patients, we anticipate that the BLA submission will cover the entirety of the Fabry population aged 18 years and older.

In the other STAR study update, all 18 patients who started the study on ERT are now successfully off ERT and the first patient has been withdrawn from ERT recently achieved an impressive 3 years of ERT. That is a significant achievement. More broadly, with the longest treated ST-920 patient recently achieving 4 years of follow-up, our data continue to look encouraging with all patients achieving and maintaining physiological or supraphysiological level of plasma alpha-Gal A enzyme activity to date.

In terms of next step, we have begun to execute BLA readiness activity and continue to advance ongoing business development discussions with potential collaboration partners. We are also committed to working with the European Medicines Agency, or EMA, to identify the optimal regular path forward in Europe and following a successful PRIME kickoff earlier this year, are preparing for continued discussions. Our hope is to be able to arrive at an aligned approach across the regulatory agencies and we anticipate sharing a regulatory update in early 2025.

Moving now to giroctocogene fitelparvovec, an investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A. On December 9, Pfizer plans to present detailed data from the Phase III AFFINE trial in an oral presentation at the 66th ASH Annual Meeting and Exposition.

The ASH abstract, which was released last week, confirmed that the AFFINE trial met its primary endpoint of non-inferiority and superiority with a statistically significant decrease in total annualized bleeding rate, or ABR, from week 12 to at least 15 months of follow-up post infusion compared with routine Factor VIII replacement prophylaxis treatment. Key secondary endpoint as defined by the trial protocol, the percentage of participants with Factor VIII activity greater than 5% at 15 months or ABR for treated bleed were met and also demonstrated superiority compared to prophylaxis. Notably, giroctocogene fitelparvovec was generally well tolerated with no study discontinuations.

These data further validate our effort to discover and develop genomic medicine with the potential to improve the lives of patients. Partnering with an organization with strong commercialization infrastructure and experience as well as a broader franchise in this area was important to us as we enter into hemophilia A partnership with Pfizer. We greatly appreciate Pfizer's leadership of this important program.

Pfizer has advised us that they are discussing the Phase III AFFINE data with regulatory authorities. 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 from this program, if approved and commercialized.

These important advances allows us to focus on our core mission to treat debilitating neurological disorders with innovative genomic medicines. We believe our ability to combine potent zinc finger epigenetic regulation payloads with exciting new industry-leading capsid delivery technology could unlock the potential of our neurology pipeline and change the treatment paradigm for neurological indications for which delivery of treatment to the central nervous system has historically been challenging.

This quarter, we submitted an IND application to the FDA for our Nav1.7 program or ST-503 for the treatment of intractable pain. Neuropathic pain can be caused by a broad array of pathologies impacting the central or peripheral nervous system. such as surgical trauma, spinal cord injury, nerve compression, neurological and infectious diseases or metabolic and hereditary syndromes. ST-503 is not intended for sporadic or acute pain like a toothache or bunionectomy, but for intractable chronic pain that completely dominates and often destroys the life of patients over many years.

Assuming FDA clearance of the IND, the Phase I/II study will assess the effectiveness of ST-503 in addressing idiopathic small fiber neuropathy, or ISFN, a peripheral neuropathy that results in highly debilitating syndromes of burning, prickling, stabbing or lightning-like pain. ISFN has an estimated prevalence of at least 43,000 patients in the U.S. and more broadly, peripheral neuropathy are estimated to affect nearly 40 million Americans.

Antidepression, anticonvulsant, opioid or topical therapy can be tried, although no long-lasting or curative therapy are currently available for ISFN patients, leading to a high unmet medical need for this patient population. A significant body of evidence implicates sodium channels in mediating the pathophysiology of neuropathic pain. ST-503 use an adeno-associated virus or AAV vector carrying an engineered zinc finger repressor to specifically target the human gene SCN9A that encodes the Nav1.7 channel -- sodium channel and is critical for pain signaling.

Developing small molecules that specifically target Nav1.7 is challenging due to the high structural similarity between different sodium channels, making it difficult to achieve selectivity and avoid off-target effects. By directly targeting the SCN9A gene, ST-503 was shown to selectively reduce the expression of 1.7 sodium channels in sensory neurons in animal model and significantly reduce hypersensitivity following a single intrathecal administration. Sangamo's preclinical research has shown ST-503 to be well tolerated in nonhuman primate and substantial Nav1.7 reduction was observed with no off-target effects.

This preclinical data, which demonstrate the potential of ST-503 as a therapy for chronic neuropathic pain, are elaborated upon in more detail in a manuscript published in BioArchive earlier this quarter, which is also available on the Presentations and Publications section of our investor page on sangamo.com.

We expect to start the Phase I/II in the middle of 2025. This represents a transformational step forward for Sangamo as the first of our neurology program to progress to the clinic. It is hoped that if efficacy is demonstrated, the application of ST-503 could be broadened to patient population suffering from other types of chronic neuropathic pain.

Moving now to prion, clinical trial authorization, or CTA, enabling activities continue to advance for our program to treat prion disease, which leverage our novel STAC-BBB capsid. As a reminder, prion disease represents a group of conditions with a devastating unmet medical need, which we believe our technology can address.

With more than 1,500 new patients diagnosed each year across the U.S. and Europe, this is a disease that is rapidly progressing and always fatal, usually within 12 to 15 months of symptom onset and with no currently effective treatment option available. In October, we presented updated data at the Prion 2024 Conference, which demonstrated the potency of our zinc finger repressor in a disease mouse model at multiple dose levels. The zinc finger repressor significantly reduced expression of prion mRNA and protein in the brain, extended mouse survival and limited the formation of toxic prion aggregates. Additionally, nonhuman primate data at Prion 2024 highlighted that a single intravenous administration of the prion zinc finger repressor delivered via STAC-BBB resulted in potent and widespread repression of the prion gene in transduced neuron. A CTA submission for this program is expected in the fourth quarter of 2025.

I will now hand it back to Sandy for closing remarks.

[Alexander Macrae, executive]

Thank you, Nathalie. In closing, we are delighted with the momentum being generated this year and are committed to the continued advancement of both our wholly owned and partnered programs.

In 2025, Sangamo science could lead to BLA submissions for up to 2 separate gene therapy programs that we believe have the potential to fund the neurology company in the long term. We plan to dose patients our first-ever neurology epigenetic regulation study. And we plan to submit an IND for the second study, which would be the first-in-human study of our novel proprietary STAC-BBB neurotropic capsid. We are also currently engaged in advanced business development discussions for our new potential STAC-BBB collaborations. This is remarkable progress for a company of our size.

We are pleased to have delivered these milestones in 2024 and plan to continue executing on our strategy in the coming months as we complete the task of transforming Sangamo into a neurology genomic medicine company. We see an exciting future as we make progress in addressing our long-term financing needs and look forward to building upon this year's progress in 2025 as we further advance our therapies to patients in need.

Operator, please open the line for questions.

[Operator]

[Operator Instructions] Our first question comes from Gena Wang from Barclays.

[Huidong Wang, analyst]

Congrats on multiple achievements here. So maybe I'll just focusing on Fabry program. Two related questions. The first one is regarding the FDA comments that eGFR slope at 52 weeks can serve as intermediate and clinical endpoint. Does that mean FDA wanted to see [ statistics significance ]of the end of the 52 eGFR compared to the baseline? And then eGFR slope at the 104 weeks may be assessed to verify clinical benefit. Can you elaborate what does that mean? Do you need to continue to show [ statistics significant ] benefit compared to baseline? Or do you need to show positive trend continue at the 104 weeks?

And the second question is related to the strategy. I think, Sandy, you mentioned, I think that that has been a while that you wanted to -- seeking partnership for this program. And now given the latest update, what is your latest thinking regarding this program that you think it will be most value generative for the shareholders? So would that be keep in-house or seeking partnership? If seeking partnership, what kind of evaluation you will be looking for?

[Alexander Macrae, executive]

Thank you, Gena, for the questions. So I'm going to pass on to Nathalie. We haven't given details of the statistical analysis that the agency have asked us to do. It really is incredible that the -- both the -- the eGFR is shown to be a positive slope and also that the agency has embraced this and agreed to accelerated approval at 1 year.

Nathalie, can you add some color to this?

[Nathalie Dubois-Stringfellow, executive]

Yes. Thank you. Yes, we're delighted to have a clear regulatory pathway to accelerated approval that could bring this drug sooner to the patient. So the FDA has agreed that the data can serve as the primary -- at 52 weeks can serve as the primary basis for approval under the accelerated approval program using the eGFR slope at 52 weeks across all patients. And this is an intermediate clinical endpoint that will give us accelerated approval. And there is -- just as a reminder, there is no limitation placed on biologic product granted accelerated approval.

In addition, the FDA indicated that the data from the 104 weeks can use to confirm clinical benefit. So we see that there is no need for any additional study. And we will have those discussions during the pre-BLA meeting with the FDA. But we anticipate that we will present the 2-year data for the 32 patient in 2026 for full approval.

[Alexander Macrae, executive]

Yes, Gena, this is quite important to get clear because I know that a number of people conflate accelerated approval with a confirmatory study. I want to be absolutely clear that no confirmatory study has been asked for or is required.

We will submit the data for the 1 year, at which point there will be 32 at 1 year, but also 19 of them will already have reached their 2-year point. We anticipate that we would be submitting the full 2-year data set a year later. The agency has said that they would recommend looking at this as confirmation of the 1-year data.

What's been really interesting is when we've looked at the patients that have reached 2 years already is that the 1-year predicts the 2-year data. So the patients are positive at 1 year, it predicts that they'll also be positive at 2-year. So this is exciting for Sangamo because all of a sudden, the BLA filing has been pulled in 3 years. We're doing everything possible to drive this forward to make sure we get it to patients with a filing in the second half of next year. As to your other question about partnerships, as you can imagine, there's a number of people have been very interested in these results.

It's wonderful when we can announce a partnership around a quarterly call. Unfortunately, these things just take time and we've almost had to refresh the partnership discussions with this new data. We hope to be able to share more about it in the near future.

But what we want to do is make sure we do a deal that gets it to patients with a filing in the second half of next year and a launch sometime in the first half of '26.

I hope that answers your question.

[Operator]

Our next question comes from Yanan Zhu from Wells Fargo.

[Unknown Analyst]

This is [ Kwan ] on for Yanan. So our questions are also around the Fabry program. Can you share with us when may we see next data update from the program?

[Alexander Macrae, executive]

Nathalie?

[Nathalie Dubois-Stringfellow, executive]

Yes. So now our Phase I/II has become a registrational study. So we are being very careful about disclosing the details of the data. And we expect to have the data in the second quarter of 2025 and share at that time the top line data.

[Alexander Macrae, executive]

So to be clear, the patients -- the last patient joined this study in April of this year. The last patient last visit will be April of next year. It then takes some period of time to clean the data and that will allow us to submit the data in the second half of next year.

Once we have that data cleaned and prepared, we will look for the best opportunity to share the data with all of you.

[Unknown Analyst]

Got it. And some quick follow-up. So for patients with longer follow-up, you mentioned that they still have a positive eGFR slope. But do you see any change in the slope when patients' follow-ups get longer?

And also in the ERT patients, do you see any change in the eGFR slope when patients stop -- withdraw their ERT?

[Alexander Macrae, executive]

So there are so many questions that I'm sure we would all like to discuss about this data and we look forward to sharing it at the right time. What I can say is the longest-lasting patient in the study is over 4 years and 4 months. And those are the patients who are in the lowest dose of the dose escalation study and they're doing very well. And the alpha-Gal continues to be produced at similar levels, which is very encouraging. There are so few patients out at that time that to do an eGFR slope would not be wise until more patients get to the longer time points.

Nathalie, anything?

[Nathalie Dubois-Stringfellow, executive]

Yes. And I can also confirm that the positive eGFR slope that we are observing at this point is across all patients, whether they're started on ERT or they're naive or pseudo-naive, whether they're male or female.

[Operator]

Our next question comes from Maury Raycroft from Jefferies.

[Maurice Raycroft, analyst]

Congrats on the progress. As a follow-up to Gena's question earlier, I think you've mentioned you could include propensity match control data, too, as part of the filing package.

Just wondering if you can comment on whether FDA will put more weight on comparing versus baseline or versus the propensity match control data. And can you talk about where you are at with getting the propensity match control data? Is that something that you think you will need in order to maximize potential with the partnership?

[Alexander Macrae, executive]

So we can't comment -- we're unable to comment on how the agency will weigh the different pieces of data. What I can say is that throughout the discussions, they have said it's the totality of the data. So it's the eGFR, both compared as a group rather than individuals, compared as a group from baseline to 1 year and then 2 years compared to what's historically recognized for Fabry disease where there is over 5-point drop over the course of the year. What's known about the ERT agents where there's between 1.5 and 2.5 reduction over the course of the year.

But they'll also be looking at the sustained effect of alpha-Gal, the sustained control of lyso-Gb3, the alpha-Gal levels in the skin biopsies are significantly increased. They'll be looking at SF-36, the patient reports about pain, about FOS-MSSI. It's the whole body of this data set that is so compelling.

And everyone on ERT, I think this is just important to remind us, everyone, the 18 patients that came in on ERT have been taken off ERT and are very happily off ERT. So it's a really compelling data set of which the eGFR is like the thing that allows the agency to give us -- find us a way to approval, but is supported and made better by the totality of the data.

[Maurice Raycroft, analyst]

Got it. Yes, that all makes sense and it's helpful. And just wanted to clarify too for the milestone payment from Genentech for the $50 million. Did you receive all $50 million? Or was there $40 million recorded this quarter? And will you get an additional $10 million from the tech transfer? Just wanted to clarify on that.

[Prathyusha Duraibabu, executive]

Maury, this is Prathyusha. Yes, we've received all of the $50 million. Only a portion of it, the $40 million was reflected in our quarter-end balance, which is what you're trying to bridge to.

[Operator]

[Operator Instructions] Our next question comes from Luca Issi from RBC Capital.

[Luca Issi, analyst]

Obviously, congrats on the regulatory alignment. Maybe 2 quick questions here for me. On Fabry, at high level, can you just talk about how your conversation with the FDA has evolved over time? I find it fascinating that the FDA asked AVROBIO to run a head-to-head trial versus Fabrazyme using renal biopsies as the primary endpoint, not too long ago versus it sounds like the FDA is telling you that single arm looking at serum biomarker is now sufficient. So what has changed there in your view? Again, any color there would be much appreciated.

And then maybe on hemophilia A, maybe in the context of the BioMarin commercial debacle, if you will, how confident are you that Pfizer really will put a lot of energy and resources behind the approval and the commercial launch of this therapy?

[Alexander Macrae, executive]

Important questions. So I don't remember how long ago that AVROBIO had the discussion with the agency. Was it 2, was it 3, 4 years ago, where they were using preconditioning cell therapy to try and show the agency that there was a benefit to their medicine.

And at that time, there were several companies, 4DMT, Freeline and others that were in the Fabry world. And then you fast forward and many of these have dropped out. And the other piece that's changed, I think, is Peter Marks' position at CBER, where he realizes that there is limitations on what can be required of small populations of genomic medicines for rare diseases and that he wants to help us, all of us, find a path forward for this. And so I think what Sangamo has agreed with the agency is simply the -- what Peter has been saying made into a plan for a very effective agent.

Nathalie, do you want to just walk through the time line of how we got there?

[Nathalie Dubois-Stringfellow, executive]

Yes. So as you might recall, we had a Type C meeting earlier in 2024, where we agreed with the FDA to do a Phase IIb study with 25 patients for the basis of approval. Then after this, we had another data cut from our trial, STAR trial and realized that we had a positive eGFR slope in 18 patients that had more -- 1 year or more and also 6 patients at 2 years. At that time, we had scheduled a prime meeting with EMA. So this was our prime kickoff and in attendance with the FDA, in the spirit of global -- the FDA and EMA approach to have a global approach to approval for rare diseases.

At that time, we presented to EMA the eGFR slope data and the FDA in attendance was very encouraged by this and asked us to submit the data to the FDA. So because we have RMAT designation, we decided to do a Type B meeting where we describe our results to the FDA and ask if given this remarkable data of a positive eGFR slope in our 18 patients at 1 year, we could use eGFR slope as the primary basis of approval on an accelerated approval pathway in our Phase I/II study, alleviating the Phase IIb study that was originally planned. And the FDA agreed with our approach and that's where we are today.

[Alexander Macrae, executive]

And I should say, in all my many years of working with the FDA, I've never seen a written response so clear. When asked if we could use the 12-month eGFR for accelerated approval, they said, yes, we agree. So we are very pleased with that. I think it hopefully is somewhat of a precedence for other rare diseases companies. They're trying to do their very best for patients that are in incredibly difficult circumstances.

If I could switch to your second question, which was your reflections on the BioMarin launch of ROCTAVIAN. We are in a relationship with Pfizer. And so we're always very careful to reflect what Pfizer has told us. And before each conference call, we agree with them what it is, how they would like their medicine to be reflected. We're very pleased with the abstracts they're going to be showing at ASH. And I would encourage you to look at the data there and read from Pfizer's language about their enthusiasm for this product.

But they have told us that we can say that they're in discussions with regulatory authorities. And that, to us, suggests Pfizer's continued enthusiasm for this product.

[Operator]

Our next question comes from Ritu Baral from TD Cowen.

[Ritu Baral, analyst]

Sandy, since the FDA endpoint revolves around renal function, are they requiring or requesting any proportion or quantum of data from the pivotal data set be from female Fabry patients or patients with cardiac variant?

And if the answer is no, would you still be able to have some of that prospective data either in the open-label portion or from some other prospective analysis for a likely label at some point?

Just as the cardiac variant and cardiac involvement of the disease gains importance, it might be an important commercial tool to have talking to the broader patient population.

[Alexander Macrae, executive]

So the discussion with the agency has been that this is for Fabry. It hasn't been for men versus women or renal versus cardiac. It's been all Fabry patients, naive, pseudo-naive ERT, experienced men and women. Our discussions with them have largely been about eGFR because we have this remarkable data. And we will look at all the other pieces of the data set in the submission.

I'll say again that when we measure alpha-Gal in the skin biopsies, it's increased. When we look at the renal function, it's increased -- or, sorry, it's improved. When we look at the patients' report of sweating, of how they feel of the FOS-MSSI, there is improvement across all of it. So one would expect that there's no reason why it wasn't having an effect on the heart as well as other parts of the body.

And the 32-patient data set is all that the agency has asked for. There will not be additional patients put in after that as part of the Sangamo clinical development program.

Nathalie, however, the patients are very keen that this gets to them as soon as possible. You met -- your team met with the Fabry support group recently. Do you want to talk a little of what they heard?

[Nathalie Dubois-Stringfellow, executive]

Yes. We were at the National Fabry Disease Foundation Patient Conference about 3, 4 weeks ago and we held a patient group forum where we had patients that were on ERT, but we had also 3 patients that were -- had received our gene therapy. And these patients are really very happy to have made that decision to enter the trial. We have patients that report that they were working with cane. They now have dropped their cane. They're working normally. They feel so much better, "patient feel like it has a new lease on life." We have patients that have reduced pain. We have patients that now are taking job in the heat in the airport, carrying luggage and they're sweating and they feel great. So it's a general well-being that we're hearing from the patient.

The patients that are on ERT are not very happy about their treatment. First of all, it's very burdensome. Every 2 weeks you get a 5 to 6 hours infusion. Often, you have someone coming at home, you have to organize this. It's pretty invasive.

And really, what we've heard from the patient is after 10 days of their ERT, they start feeling not well. They're starting to have symptom coming back and they still have to wait. And they have other medications that they're taking around the ERT pre or post. So it's really not a very good treatment for the patient side.

And because it's burdensome, we know that there is a large population of Fabry patients that do skip doses because of the burden of ERT treatment.

[Alexander Macrae, executive]

Yes. We are very clear that ERT was a great advance in the treatment of Fabry. And we feel that this is now the next stage in that journey where they'll be able to get a single infusion of AV, extremely well tolerated with no serious adverse events related to the treatment and show this benefit over time. And it's a privilege to work on such a medicine and we look forward to finding the right partner to take this forward to get it to patients.

[Operator]

The question-and-answer session is now closed. I'll now turn it back over to Louise Wilkie for closing remarks.

[Louise Wilkie, executive]

Thank you and thank you once again for joining us today and for all of 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. Thank you.

[Operator]

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