Sangamo Therapeutics, Inc.

Good afternoon and welcome to the Sangamo Therapeutics fourth quarter and full year 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. Please go ahead.

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 McRae, Chief Executive Officer, Natalie Dubar-Stringfellow, Chief Development Officer, and Pratisha Durrababu, Chief Financial Officer. Slides from our corporate presentation can be found on our website, sangamo.com, and 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 and value of Sangamo's product candidates and technologies. Sangamo's ability to earn and receive payments from its collaboration and license agreements. Sangamo's expectations regarding new collaborations and license agreements. the anticipated plans and timelines of Sangamo and its collaborators for clinical trials, clinical data presentations and releases, regulatory submissions, regulatory approvals, upcoming catalysts and milestones, and other statements that are not historical fact. Actual results may differ materially from what we discussed today. These statements are subject to certain risks and uncertainties that are discussed in our filing for the SEC, specifically in our annual report on Form 10-K. The fiscal year ended December 31, 2024. and subsequent filings and reports that Sangoma 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 McRae.

Thank you, Louise, and good afternoon to everyone joining the call today. Sango's pipeline has made a great deal of progress since the start of 2024. We have advanced our prioritised neurology therapies towards the clinic, securing our first-ever neurology IND in idiopathic small fibre neuropathy for chronic neuropathic pain and demonstrating non-clinical proof of concept for a product candidate in prion disease. We showed that we are a collaborator of choice for neurotropic capsids with the announcement of two blue-chip pharma agreements for our industry-leading delivery capsid, STAC-BBB, the first with Genentech for tau and a second neurology target, and the second with Astellas for up to five neurology disease targets. We have a clear regulatory pathway to accelerated approval in Fabry disease, which could reduce the time to potential approval by approximately three years. And our Fabry-June therapy study continues to generate best in class data with a pivotal data readout expected in mid 2025. From a financial standpoint, since 2023, we have reduced our non-GAAP operating expenses by nearly half year over year. And in 2024, we raised over 100 million in funding through non-dilutive license fees and milestone payments, as well as equity financing. And these are significant achievements for a company of our size. Judged by all other metrics, this would have been a very successful year. However, we know until we partner Fabry and appropriately capitalise the company for success, our work is not done. I want to re-emphasise that our number one priority continues to be addressing our financial needs. Sangamo must be well capitalised to fulfil our potential. We continue to engage in Fabry business development negotiations and securing a commercial partner is our key focus. Interest in this program has been strong. This is proving to be a time consuming process as discussions of this nature are complex and facilitating the extensive due diligence required by potential partners takes time. We remain committed to securing an anticipated partnership in the second quarter of 2025 that is best suited to bringing ST920 to Fabry patients upon potential approval and that provides capital for Sango to execute on its other programmes. We will share information as soon as we are able. Furthermore, we are actively engaged in advanced contract negotiations with a potential collaborator for third stack BBB license agreement and are hopeful of having more news to share near the end of this quarter. I would now like to hand it over to Natalie, our Head of Development, who will walk us through detailed pipeline developments. Natalie.

Thank you, Sandy. First, I'd like to provide updates on SC503, our investigational epigenetic regulator for the treatment of chronic neuropathic pain, which is ready to enter the clinic. Our initial indication is an idiopathic small fiber neuropathy, or ISFN, a peripheral neuropathy that results in highly debilitating symptoms, such as burning, prickling, stabbing, or lightning-like pain, that is estimated to impact about 43,000 people in the United States. More broadly, peripheral neuropathy are estimated to affect nearly 40 million Americans. As we've shared previously, a significant body of evidence implicates sodium channels in mediating the pathophysiology of neuropathic pain. SC503 is a zinc finger repressor, or ZFR, targeting the human gene SCN9A that encodes the NAV1.7 sodium channel. Developing small molecules that specifically target NAV1.7 is challenging due to the high structural similarities between different sodium channels, making it difficult to achieve selectivity and avoid off-target effects. We believe our epigenetic regulation approach is differentiated. By directly targeting the SCN9A gene, ST503 has shown to precisely and potently reduce the expression of NAV1.7 sodium channel in sensory neurons in animal model, and significantly reduced pain hypersensitivity following a single intrathecal administration. SC503 has been well-paraded in non-human primates with no off-target effect observed. Following FDA clearance of the IND in November 2024, our first-ever serology IND, we are actively preparing for a Phase I-II study to assess the safety, durability, and preliminary efficacy of a one-time dose of ST503 administered intrinsically to patients with intractable pain due to ISFN. This multicenter, double-blind, randomized, sham-controlled dose escalation study is designed to evaluate three ascending doses. beginning with what we believe to be the minimally efficacious dose as determined from animal studies. Patient will be randomized in a two to one ratio to receive either SC503 or a sham treatment with three patient plan in each of the first two dose cohorts and up to nine patient in the top dose cohort. The primary objectives of this phase one two study will be to assess the safety and durability of SC503 with secondary objective to assess preliminary efficacy based on the impact of ST503 on refractory pain and assessment of the multidimensional impact of ST503 on sleep, mental health, and quality of life. We strongly believe in the potential of ST503 to reversionalize the chronic pain landscape. And if successful, significant opportunity exists to broaden its application to patient population suffering from other types of chronic neuropathic pain. We plan to begin patient enrollment and dosing in mid-2025 and anticipate having preliminary proof of efficacy data in the fourth quarter of 2026. Moving to our prion disease program, we continue to advance clinical trial authorization or CTA-enabling activities and expect a CTA submission in the UK in the first quarter of 2026. As a reminder, this program leverages our novel stag BBB capsid, which, if safe and effective, could validate our broader neurology pipeline. Prion disease is a rapidly fatal and incurable neurodegenerative disease caused by the misfolding of the prion protein encoded by the PRNP gene. At least 1,300 new cases of prion disease are identified each year in the United States and in Europe with a similar presence globally. This quarter, we published a manuscript in bioRxiv demonstrating nonclinical proof of concept for our epigenetic regulation approach. A single intravenous infusion of our ZFR significantly reduced expression of prion mRNA and protein in the mouse brain, extended mouse survival, and improved an array of molecular histological biomarker and behavior readouts, even when administered post symptomatically to mice with prion disease. In addition, a single intravenous administration of the prion ZFR delivered to non-human primates resulted in potent and widespread reduction of prion expression in transuse neurons throughout the brain. This is a significant result in a highly challenging disease with no treatment options today. We plan to begin clinical trial enrollment and dosing in mid-2026 and expect to have preliminary clinical data in prion disease in the fourth quarter of 2026. Moving now to Fabry. At the World Symposium in February, we presented impressive updated preliminary clinical data from our Phase I-II STAR study of isaralgalgine Sivaparvovac, or ST920, our investigational gene therapy for the treatment of Fabry disease. This latest data, which shows significant sustained benefit improvement in kidney function and a favorable safety profile, continue to demonstrate the potential of ST920 as a one-time durable treatment option for Fabry disease that can improve patient outcomes. In the 33 patients treated with ST920, elevated expression of alpha-gal A activity was maintained for nearly four years for the longest treated patient. Importantly, we observe a positive mean EGFR slope of 3.061 millimeters of cleansed blood per minute per body surface in the 23 patients with at least one year of follow-up, indicating notable improvement in renal function. For context, the average untreated patient in Fabry disease has an EGFR slope of minus three or minus four, so this statistically significant positive EGFR slope is a remarkable achievement. All 18 patients who began the study on enzyme replacement therapy, or ERT, have been successfully withdrawn from ERT and remain off ERT. We also observed notable improvement in quality of life among the patient with at least one year follow-up. For example, among the short-form 36 quality of life score, we saw a mean change in the general health score of 10.6, as well as significant improvement in physical component bodily gain, physical vitality, social function, and emotional well-being scores. The FDA has provided us with a clear regulatory pathway to accelerated approval for ST920 using EGFR slope at 52 weeks across all patients as an intermediate clinical endpoint. The 52 weeks EGFR slope data from all enrolled patients in the Phase I two-star study will be available in the first half to 2025. We are thrilled with how the data are progressing and look forward to providing future update as the full 52 weeks data become available in the middle of this year. We're actively preparing all necessary activity for the BLA, including manufacturing readiness, and continue to work towards a potential BLA submission in the second half of 2025. We're excited that this potential medicine could be commercialized as early as the second half of 2026. which would be an incredible achievement for Fabry patients in need. I will now hand it back to Sandy for closing remarks.

Thank you, Natalie. In closing, we're pleased with the progress we've made this year as we transition to becoming a clinical stage neurology company. We have advanced our long plan neurology pipeline towards the clinic, securing our first ever neurology IND and with patient dosing expecting in the coming months. We have shown Sango to be the collaborator of choice for neurotrophic capsids with the announcement of two blue chip pharma agreements for STAC-BBB. And we have secured a clear regulatory pathway to accelerated approval in Fabry disease, which would reduce the time to potential approval by approximately three years. We are proud of this progress and excited to be so close to the anticipated dosing of patients in our first ever neurology clinical trial. In parallel, we remain resolutely focused on raising the additional capital needed to set Sangam up for success. As outlined earlier, we're in the very late stage business development negotiations for a third potential STAC BBB license agreement. We have compelling Fabry data with a pivotal data readout expected in the coming months. And business development negotiations for a potential Fabry commercialization agreement continue to advance with several interested partners. We believe we can solve both our short-term and long-term financing needs and look forward to providing additional updates as soon as they become available. Operator, please open the line for questions.

Yes, sir. As a reminder, to ask a question, you will need to press star 11 on your telephones. To remove yourself from the queue, you may press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Luis Santos of HC Wainwright. Your line is open, Luis. Hello, everyone.

Thank you so much for taking our questions. This is Luis for Patrick Trucchio. I was wondering if you're still waiting on any data for the Fabry program as you expect this partnership next discussions to lead to results next quarter. A similar question for the JuroVac in HEMA. Should we be expecting any more data later this year and would that facilitate any partnerships there? Thank you.

Thank you, Luis. The Fabry partnership, we would love to have announced it. We're in late phase discussions across several potential partners and look forward to taking that forward and finding the right place for the patients and for the right partnership for our shareholders. These things take time. The route forward from the agency was as recently as end of October. We've had to compress the planning for the file and launch from what was three, three and a half years down to six months to the filing and then to the launch. And so there's a huge amount of activities that are going on. What I can reassure you is the data that Natalie and her team showed at the World Symposium remains positive, remains very positive. And we look forward to seeing the one year data for the last patient as soon as next month. And that will allow us to drive this forward. Now it's a matter of closing the deal and making sure we find the right partner. For the haemophilia, That was returned to us or the termination notice was given over the holiday period. And the more we see from Pfizer, the more we realize that it really was days away from both U.S. and a European filing. Our team are sitting closely with the Pfizer organization to understand and explore all possibilities for a transition. Ideally, we would like to hand this directly to a partner without having to go through Sangamo, but these are very early days to be able to give you a commitment to that plan. What I can tell you is that we've already had incoming interest on the haemophilia program. But I don't want to overpromise until we have a chance to understand all the data and speak with potential partners.

Just to clarify, do you get the rights to all of the data? Will you have access to all of that and you will be able to share at some point?

We will have access to all the data from Pfizer. It's very clearly laid out in the contract. But that's a huge amount of data for something that was about to be filed in but a few days' time. And like you, we respect the idea that if someone goes into a clinical trial, you have a responsibility to make the data available.

Thank you so much.

Thank you. Our next question comes from Yanan Zhu of Wells Fargo. Please go ahead, Yanan.

Hi, thanks for taking our questions. This is Quan Ang for IANA. So our question is also around Fabry. So can you share, have the interesting party have seen any data beyond the world symposium data? I think that data has a data cut in, I think, September 2024. So any updated data potential partner have seen beyond that? Thank you.

I'm looking to Natalie here and who's shaking her head. We believe they haven't seen any efficacy data beyond what was seen.

Yes.

They have seen lots of other data. They've seen data about the manufacturing, about the CMC process. They've seen broader versions of the data cut that you saw, but they haven't seen later data. We now have seen data for up to the 30 patients, and there's only two more patients to complete their journey before we have the complete data set and can pull that together for the file.

Got it. That's super helpful. And for the 30 patients data you have seen so far, is the EGFR data consistent with what you have presented previously?

You can understand. I can't give you more details, but we remain very encouraged by the data set and look forward to filing it because we feel that it's fulfilling all that the agency is asking for. Super helpful. Thank you so much.

Thank you. Our next question comes from Mari Raycroft of Jefferies. Please go ahead, Mari.

Hi, thanks for taking my question. I was going to ask on the STAC BBB deal, just clarifying on that. You said you could have that in place by the end of this month. Is that correct? And then is there more you can say on what the upfront for that one could look like?

So I think you could look at what we've got as upfronts for the previous two deals. There's now almost like a standard market price for those deals. Yeah, we're guiding at the end of the year. We hope at the end of the quarter. Thank you, Louise. We had hoped to have done it in time for this quarterly call. And just these things are not always in our hands. But we know that the partner is one that you will find a very logical blue chip choice. And we feel that we are putting a capsid in the hands of another great company that will allow their neurology pipeline and ours, frankly, to advance.

Got it. That's helpful. And just a quick question on OpEx, just how you're thinking about that going forward and once you solidify the partnership for Fabry. how that can change. Patricia.

Hi, Mari. How are you? From the OPEX itself, we've done everything proactively within our control. We've reduced our OPEX by nearly half over year over year. And we've defined our OPEX 425 to be very focused on taking our neurology pipeline forward So, from our guidance perspective, we've guided to keeping the same level of OPEX as last year as we move both now 1.7 and pre-on forward.

Understood. Okay. Thanks for taking my questions.

Thank you. Once again, to ask a question, please press star 1 1 on your telephone. Again, that's star 1 1 on your telephone to ask a question. Our next question comes from Nicole Germino of Truist. Please go ahead, Nicole.

Good afternoon, and thanks for taking my question. So, there's some literature around hypotension associated with inhibition of NAV 0.1 channel, sodium channels. So, I have two questions. Do you have any hypotheses on how and why you're not seeing any hypotension so far in animal models or rather, maybe how do you get investors comfortable around any potential hypotension concerns? And then second question, can you help us understand the patient enrollment criteria for patients enrolling into the NAV 1.7 study?

Natalie, can you talk to these?

Yes. So, you know, we have... not seen any effect on hyper or hypotension in all our animal study, especially in the NHP study where it's a GLP study where we monitor those functions very closely. I think the NAV1.7 relationship with hyper or hypotension is not really well established. I think there is one report on a small molecule that was reported and the the protein was, the small molecule was delivered IV to the general, and we don't know the specificity. We don't have that information. So I think it's too early to make the conclusion that NAV1.7, or there's not enough evidence to show that NAV1.7 could impact IPR or hypotension.

And all the monkeys are closely monitored. The blood pressure is monitored.

Absolutely.

There is no... They've all done very well. So we feel it's a very different situation.

And then it's also intrathecal as well, right? Intrathecal administration.

It's intrathecal, yes.

And there was a second question.

On the patient enrollment criteria. So we're targeting patient with ISFN. as mentioned, and, you know, there is a bunch of inclusion-exclusion criteria that will be highlighted when we publish the clinicaltrial.gov design in, you know, design and public.gov. So is there anything specific you're looking for?

Just overall the patient description for the SFN patient population, if there's anything that... if there's anything of note.

I don't think so. There's always a balance between having as pure a population and trying to avoid comorbidities. And that's always a fine needle to find. path to try and execute, but I think the team have done a nice job of getting a recruitable study that will give us a clear answer. I think it's important to emphasise that this is a one-time treatment and therefore the benefit risk is really important and therefore a clear result is what we need to look for for the powerful effect that we believe, if the animal models are replicated, that this molecule should achieve.

Great. Thank you so much.

Thank you. Our next question comes from Jenna Wong of Barclays. Please go ahead, Jenna.

Thank you. I have two sets of questions. First one is regarding the February deals. Just wanted to know that the delay on February deal, the potential HQ, was that due to the deal term agreement or is that because the potential partner wanted to see additional data or regulatory certainties? And then are you still looking for DOTOM to cover the, I think, almost two years OPEX until you reach, let's say, 4Q26, be able to show the proof concept data from both internal program? And the second question is regarding the 503. 4Q26 data update. do you expect to identify going forward dose and what is your goal of a placebo-adjusted pain score reduction?

So, Gina, thank you for your questions. The FABRI discussions are going well. The clinical results are so compelling that each of the partners is fascinated by it. We can't discuss the terms and we can't discuss what we're in negotiation over. I'm sure you understand that. But the overall goal of Sangamo has to be to get us well funded to get to that point at the end of next year where we can demonstrate the effect of NAV1.7 and hopefully show early results for prion disease. So that's our overall mission. And as we get closer and closer to the pre-BLA meeting in the summer and the file by the end of the year, you can imagine that the energy around the discussions increases. And Natalie, you had a question as well, didn't you?

Yeah. Yes. On the SC503, so to be successful, our product candidate needs to demonstrate both near-term efficacy and long-term effect. In our trial, we hope to see a reduction in pain within the first 12 weeks. We understand the placebo effect, which is an important consideration, and as we've planned for our Phase I-II study design. But you have to consider also that it's a one-time therapy, so our approach is very different to traditional therapy where the placebo control has been documented, where then the sham treatment are taken regularly, which really can straighten the reminder of the placebo effect. So just as a reminder, this is a one-time potential treatment with one injection, and we believe the placebo effect will start to wane as we get further away from the point of administration. And as I mentioned, you know, we think looking at the data in from the animal study that really we should have a near-term efficacy fairly quickly. In our animal study, I would say that the effect is maximal and plateau at about three to four weeks after administration.

Are you looking for any placebo adjusted pain score reduction? You will be looking for like a two score or any particular scores you have in mind, giving some benchmark?

We wouldn't be wise to set ourselves a target of the amount of reduction. This is clinical science and the first time it's been administered in humans. We hope that it will be a significant effect because this is a dreadful disease and intractable pain is not something anyone would wish to have. And we look forward to sharing the results with you over the coming year to 18 months.

Thank you.

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

Thank you. And thanks once again for joining us today on the call and for your questions. As a reminder, you can access our presentation on the investor relations section of the Los Angles website. We look forward to keeping you updated on our future developments.

This concludes today's conference call. Thank you for participating. You may now disconnect.