Sangamo Therapeutics, Inc. (SGMO) CEO Sandy Macrae on Q4 2019 Results - Earnings Call Transcript

Sangamo Therapeutics, Inc. (NASDAQ:SGMO) Q4 2019 Results Conference Call February 28, 2020 8:00 AM ET

CompanyParticipants

McDavid Stilwell - SVP of Corporate Communications and Investor Relations

Sandy Macrae - Chief Executive Officer

Adrian Woolfson - EVP of Research & Development

Sung Lee - EVP and Chief Financial Officer

Stephane Boissel - EVP of Corporate Strategy

Bettina Cockroft - SVP and Chief Medical Officer

Conference Call Participants

Maury Raycroft - Jefferies

Whitney Ijem - Guggenheim Securities

Eric Joseph - JP Morgan

Aaron Welch - H.C. Wainwright

Jim Birchenough - Wells Fargo

Gena Wang - Barclays

Ritu Baral - Cowen

Mike DiFiore - Evercore ISI

Benet Gresley - Mizuho Securities

Operator

Good morning, and welcome to the Sangamo Therapeutics' teleconference to discuss fourth quarter 2019 financial results. This call is being recorded.

I will now pass you over to the coordinator of this event McDavid Stilwell, Senior Vice President of Corporate Communication and Investor Relations.

McDavid Stilwell

Thank you for joining us today. Yesterday afternoon, we issued a press release announcing a global collaboration, and earlier this morning, we issued fourth quarter and full year 2019 results.

During our call today, we'll be referencing slides from our corporate presentation, which can be found at our website sangamo.com under the Investors and Media section in the Events and Presentations page.

This call includes forward-looking statements. And these statements include, but are not limited to, the timing and scope of Sangamo's genomic medicine platform and products, the potential for Sangamo's product candidates to provide clinical benefit to patients, Sangamo's collaborations including their financial and operational impacts, Sangamo's development and manufacturing plans, and Sangamo's expectations regarding its financial performance.

Actual results may differ substantially from what we discuss today. In addition, these statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are detailed in documents that the Company files with the Securities and Exchange Commission, specifically in our most recent annual report on Form 10-K and in our most recent quarterly report on Form 10-Q. The forward-looking statements stated today are made as of this date and Sangamo undertakes no duty to update such information, except as required under applicable law.

On this call, we will discuss certain non-GAAP financial measures. We believe this measure is helpful in understanding our past financial performance and our potential future results. This is not meant to be considered in isolation or as a substitute for the comparable GAAP measures. The comparable GAAP measures and reconciliations of GAAP to the non-GAAP measures discussed on this call are included in today's press release that's available on our website.

With me this afternoon -- this morning on this call are several members of the Sangamo senior management team, including Sandy Macrae, Chief Executive Officer; Sung Lee, Chief Financial Officer; Stephane Boissel, Head of Corporate Strategy; Adrian Woolfson, Head of Research and Development; Bettina Cockroft, Chief Medical Officer; and Melita Sun Jung, Head of Business Development.

On today's call, Sandy will discuss the Biogen collaboration we announced yesterday. Adrian will provide an overview of our zinc finger platform for neurological diseases and a clinical program update and Sung will review 2019 financials.

And now, I'd like to turn the call over to Sandy.

Sandy Macrae

Thank you, McDavid, and good morning to everyone on the call. We're delighted to be here this morning. Yesterday afternoon, Sangamo and Biogen announced an ambitious and expansive collaboration to develop genomic medicines for neurological diseases, including Alzheimer's disease and Parkinson's disease.

The collaboration will leverage Sangamo's proprietary zinc finger protein or ZFP technology to modulate the expression of genes involved in neurological diseases such as tau for Alzheimer's, alpha synuclein for Parkinson's, a Neuromuscular target, and nine other neurological targets.

Upon closing the transaction, Sangamo will receive $350 million, which is comprised of $125 million upfront payment and $225 million in proceeds from the purchase by Biogen of approximately 24 million shares of Sangamo's stock at a price of $9.21 per share.

In addition, Sangamo may receive up to $2.37 billion in other development, regulatory and commercial milestone payments, including up to $925 million in pre-approval milestone payments and up to $1.4 billion in the first commercial sale and other sales-based milestone payments. Sangamo will also be eligible to receive tiered high-single digit to sub-teen double-digit royalties from Biogen on potential net commercial sales of products arising from the collaboration.

The magnitude of this collaboration reflects the true value of our zinc finger platform technology, which our experienced and passionate scientists have worked to optimize for therapeutic applications and the immense promise of genomic medicine in neuroscience. We are truly thrilled to be collaborating with Biogen, who are pioneers in neuroscience drug development and committed to the development of innovative medicines in this field.

Sangamo and Biogen agree that there is both urgent unmet patient need and the potential for medical breakthroughs in the field of neuroscience. In the case of Alzheimer's and Parkinson's, the current standard of care treatments are symptom focused and there are no approved treatments to modify or slow the relentless progression of these devastating neurodegenerative diseases.

That's why the promise of genomic medicine to provide a one-time treatment that addresses the underlying cause of disease at the DNA level is so powerful. A genomic medicine in the field of neuroscience offers a hope of potentially altering the natural history of the disease for patients.

At Sangamo, we feel a responsibility and a sense of urgency to translate our promising signs into genomic medicines that can enter the clinic. And that's why our strategy is to simultaneously develop our own proprietary product candidate pipeline and to partner when we need access to exceptional therapeutic area expertise or the financial resources to rapidly move our programs forward in the clinic.

We feel that the combination of our engineered zinc finger proteins, Biogen's unmatched neuroscience expertise, capability and infrastructure along with our shared commitment to bring innovative neurological medicines to patients, establishes the foundation for a robust and compelling partnership. We are excited to have Biogen as -- both as partner and a strategic shareholder and we look forward to working with them to advance these important programs.

As Biogen has said, they're equally excited to work with Sangamo to treat challenging neurological diseases of global significance and are committed to quickly progressing programs forward to IND applications. Our cooperation with Biogen is an excellent example of the way that our research productivity can translate into value for shareholders.

We have frequently spoken about the latent potential of our ZFP platform, a technology we believe that we can engineer to address virtually any genomic target and which is able to generate an expansive pipeline. Collaborations such as this one had enabled us to activate the potential of the technology in partnership with therapeutic area leaders and to raise significant cash to fund our new and ongoing R&D activities.

To-date, Sangamo has brought in approximately $700 million through license fees, milestones, and equity from our partnerships. In terms of future opportunities and additions to -- in addition to royalties on net product sales, Sangamo could also earn up to $6.34 billion in potential milestone payments from our partnerships cumulatively.

We are diligent and intentional in the choice of our partnerships and takes the necessary time to find the right partner and to negotiate specific rights that we are out-licensing. Today, we have entered into a strategic collaboration starting with three targets with an option for nine additional neurological targets to be selected by Biogen.

Beyond those 12 total targets, we retain the rights to the use of our technology in the hundreds of additional potential neurological disease targets and we will look for opportunities to advance additional programs so that we can bring innovative new medicines to patients and realize additional value for our shareholders. These partnerships were especially important as Sangamo enters the second wave of development, applying our genomic medicine technologies to disease areas with large patient populations and great unmet medical need.

In addition to starting our journey with Biogen, this quarter also marked an important milestone for Sangamo as we became a Phase 3 Company. We transferred the IND for SB-525 Hemophilia A gene therapy to our development partner Pfizer, who are planning to initiate a Phase 3 registrational trial later this year. This brings us one step closer to our mission, to bring our genomic medicines to patients.

Finally, before I turn the call over to my colleagues, I would like to congratulate the teams at Sangamo for the courage that has taken to trailblaze in this new era of -- a new area of genomic science and medicine and for the discipline and hard work that has been necessary to become a Phase 3 Company and to execute an unprecedented neurological disease collaboration.

I'd like to say special thanks to Stephane Boissel, our Head of Corporate Strategy and our teams in corporate development, business development and research, whose leadership and focus were instrumental in helping Sangamo enter into this important partnership.

With that, I'll turn the call over to Adrian.

Adrian Woolfson

Thank you, Sandy. Yesterday afternoon, we were delighted to announce our new collaboration with Biogen to develop Sangamo's proprietary engineered zinc finger protein technology into genomic medicines for neurological diseases of global significance.

The ability to switch genes on and to switch genes off in the brain precisely and with great specificity is a really exciting new development in the application of genomic medicines in neuroscience. The first product candidates in the collaboration ST-501 targeting tau and ST-502, which targets alpha synuclein, leverage Sangamo's pioneering genome regulation technology, zinc finger protein transcription factors, ZFP-TFs, which are currently delivered using adeno-associated viruses AAVs and function at the DNA level to selectively repress or activate the expression of specific genes to achieve the desired therapeutic effect.

Last year, Sangamo published a manuscript in Nature Medicine detailing the high selectivity, genomewide specificity and the long-term tolerability of zinc finger proteins TFs in preclinical models of Huntington's disease that provided proof of concept for this technology.

ZFP-TF can be engineered for a wide range of applications within the neurological disease areas space including for single gene tunable pan-allelic regulation of targets such as tau or alpha synuclein or Allele-selective repression as is the case with our Huntington's and ALS programs. This technology also has many potential applications beyond neuroscience as it allows gene expression to be tuned to therapeutic levels in any cell type.

Sangamo's differentiated ZFP-TF technology provide several important benefits over other therapeutic strategies that are currently under investigation. In the case of neurodegenerative diseases such as Alzheimer's and Parkinson's for example, there is accumulation of toxic misfolded proteins and neurons, and targeting the treatment to all the different forms of these proteins is incredibly difficult.

It is also challenging to target RNA as there are several copies of these molecules and they come in multiple forms. In contrast, however, by targeting the disease upstream with both the protein and the RNA complexity using the ZFP-TF, we were able to address the key drivers of the disease at the source, by repressing their expression at the DNA level.

Furthermore, the prospects of a one-time administration of an AAV that can restrict the expression of ZFP-TFs to specific cell populations has many important potential advantages over other therapeutic modalities that are currently under clinical investigation. In the case of Alzheimer's disease and other tauopathies, the progressive accumulation of toxic tau protein in the brain is linked to neuronal loss and clinical symptoms.

Reducing the total amount of tau expressed within neuron has been shown to provide benefit in animal models of tauopathies. Similarly, misfolding and aggregation of alpha synuclein has been shown to play a central role in the cellular deficits associated with Parkinson's disease. Consequently, reducing the expression of tau or alpha synuclein in the brain may have the potential to slow or even to halt the progression of Alzheimer's disease and Parkinson's disease respectively.

The current marketed treatments target the symptoms of these diseases and would clearly be very compelling to have a treatment that both targets disease progression but additionally also slows or completely arrests the disease pathology. I'm really immensely excited about this collaboration because it unlocks a whole new area of medicine into the CNS.

Preclinical studies have demonstrated the ability of AAV vectors to efficiently deliver ZFP-TFs that are targeted to tau ST-501 or alpha synuclein targeted ST-502 and that results in highly specific, potent, and tunable repression of tau and of alpha synuclein.

Indeed, the preclinical data presented by Sangamo last year demonstrated significant reduction of tau expression in the non-human primate brain following administration of targeted ZFP-TFs.

We also presented preclinical data last December at our R&D Day in New York City, which showed that more than half of the ZFP-TFs tested reduced the total alpha synuclein levels by greater than 50% in ex-vivo cell culture system. We are very excited to work with Biogen to further develop these assets and to progress them to IND-enabling studies.

Under the terms of our collaboration with Biogen, Sangamo will take the lead on early research activities aimed at the development of proprietary neurological AAV delivery vectors and ZFP-TFs that target therapeutically relevant genes.

Following this preclinical development phase, Biogen will assume sole responsibility for the IND-enabling studies, clinical development, regulatory interactions and also commercialization.

Turning now to some clinical updates. We ended 2019 on a strong note progressing our lead asset SP-525 into a Phase 3 program with Pfizer and securing the necessary regulatory approvals to advance additional gene and cell therapy programs into Phase 1/2 clinical trials throughout the year.

Starting with SB-525 Hemophilia A gene therapy; in addition to the recent transfer of the program to Pfizer, we were pleased with the Phase 1/2 data that was presented at the ASH annual meeting in December. The data showed that SB-525 was generally well tolerated and suggest the potential for sustained Factor VIII levels following treatment. We will continue to observe the durability as the follow-up data accumulate.

Moving now to our follow-on and wholly owned gene therapy ST-920 for Fabry disease. We're currently screening patients in the STAAR clinical trial, which currently has six sites opened in the U.S. The first European site was initiated in London this week. ST-920 received orphan drug designation from the European Medicines Agency in January.

At ASH last year, we presented preliminary information from the Phase 1/2 THALES study assessing ST-400, an ex vivo gene-edited cell therapy in patients with transfusion-dependent beta thalassemia in partnership with Sanofi. We will continue to follow the data to understand the safety profile and potential clinical benefits of the treatment.

Also in partnership with Sanofi, the first patient was dosed in the Phase 1/2 PRECIZN-1 trial evaluating BIVV003, our related ex vivo gene-edited cell therapy for the treatment of sickle cell disease for which Sangamo received a $7.5 million milestone payment. BIVV003 uses an identical zinc finger nuclease mediated editing and manufacturing process to ST-400 with a mobilization regimen as the patient's cells differs.

Plerixafor is used in combination with G-CSF in beta thalassemia as compared with plerixafor alone for sickle cell disease as G-CSF is contraindicated in this patient population.

Moving on now to our first in human CAR-Treg cell therapy TX200, and we're happy to say that we recently received a number of regulatory approvals, including clinical trial application authorization in the U.K. for the Phase 1/2 STEADFAST clinical study in HLA-A2 mismatch kidney transplantation. We will continue to work closely with our oncology collaborator, Kite, as they advance KITE-037, an allogeneic anti-CD19 CAR-T therapy into the clinical trial this year.

Finally, I would like to mention that we were pleased to see the FDA's guidance on gene therapy manufacturing and clinical developments of products that was published in January. It is certainly immensely encouraging that the FDA recognizes the promise of gene therapy and is creating regulatory pathways for this new treatment modality. We very much look forward to continuing our interactions with the FDA as we further develop and progress our genomic medicine pipeline.

I will now turn it over to Sung for an overview of the financial results. Sung?

Sung Lee

Thank you, Adrian, and good morning, everyone. I'll first begin with the fourth quarter results. We reported consolidated net income of $4.6 million or $0.04 per share compared to a net loss of $18.7 million or $0.18 per share for the same period in 2018.

Revenues were $54.9 million compared to $26.8 million for the same period in 2018. The increase was primarily attributable to a $25 million milestone achieved for SB-525, our Hemophilia A candidate partnered with Pfizer and a $7.5 million milestone achieved for our sickle cell disease candidate, partnered with Sanofi. Total operating expenses were $53.4 million compared to $47.6 million for the same period in 2018.

Turning to the full year 2019 results. Consolidated net loss was $95.2 million or $0.85 per share compared to a net loss of $68.3 million or $0.70 per share for 2018. Revenues were $102.4 million compared to $84.5 million in 2018. The increase in revenues was primarily attributable to milestones achieved with Sanofi and Pfizer, as well as higher revenues related to our collaboration agreement with Kite Gilead.

Total operating expenses, excluding stock-based compensation were $188.3 million compared to $146.9 million in 2018. The increase in operating expenses was primarily related to the Company's overall headcount growth and facilities expansion to support the advancement of Sangamo's therapeutic pipeline and build-out of the in-house manufacturing facility. As of December 31st, 2019, the Company had cash, cash equivalents marketable securities and interest receivable of $385 million.

Turning to 2020 full-year guidance. We anticipate operating expenses, excluding stock compensation, to be in the range of $245 million to $260 million. This range reflects investments to support our new collaboration with Biogen, continued progress toward GMP manufacturing capability and progression of our clinical programs.

And finally, as Sandy mentioned earlier, we are excited about the potential of the partnership with Biogen. The collaboration has been approved by the Boards of Directors of both companies and is subject to customary closing conditions, including the expiration of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. This transaction is anticipated to close in the second quarter of 2020.

With the anticipated near-term cash from this transaction, combined with our existing cash balance, we have the wherewithal to execute on our wholly owned and partnered programs, potentially through Pfizer's first BLA filing of SB-525 for Hemophilia A and beyond.

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

Sandy Macrae

Thank you, Sung. This is an exciting day at Sangamo, and I'm sure you all have lots of questions. So let's just get straight to it. Operator?

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Our first question comes from Maury Raycroft with Jefferies. Your line is open.

Maury Raycroft

Hi, everyone. Good morning and congrats on the update. Seems like a great deal. To start, I'm wondering if you can say how far along the neuromuscular program is?

Sandy Macrae

Maury, thank you for your question. We haven't said anything about this neuromuscular program and it's a further unnamed target by Biogen, but it's an exciting example of their confidence in our technology.

Maury Raycroft

Got it. And then for the nine unselected targets. If Biogen does not select those by 2025, what happens? And then, for the nine targets. Can you talk about how long it could take to get a therapy ready for a target? Just generally, how resources will be used for these targets?

Sandy Macrae

Let me pass that one onto Stephane.

Stephane Boissel

Hi, Maury. So, for the first part of your question, if those target are not selected by the term of the five-year collaboration time, we would be freed from the exclusivity under the Biogen agreements. For the second part of your question, can you please repeat it, please?

Maury Raycroft

Sure. Just wondering for the nine targets, if you could talk about how long it takes to get one of them ready to actually get a product -- a program ready for it? And just generally, how resources will be used for these different therapies?

Stephane Boissel

Well it's very valuable. I think it will depend on a target per target basis. But we probably need between nine to 18 months on a per target basis and that work will be, of course, conducted by Sangamo.

Sandy Macrae

But what's been really pleasing about this platform is, how effective the team have been at targeting new genes. You saw at the R&D Day that we showed evidence about Alzheimer's which we -- tau for Alzheimer's, which we've been studying for a while. We added in synuclein, which was really only done in a very short period of time and then Prion disease, which is not part of the deal.

That's work -- it only have been going on for, I don't know, three to six months. So, we are very pleased at how quickly and effectively and successfully the team are able to create assets for new targets, and I think that was one of the things that give Biogen great confidence that we could succeed with their list.

Maury Raycroft

Got it. And then if you can talk about rights to your novel CNS AAV vectors, I guess does Biogen have any unique or exclusive rights to those vectors?

Sandy Macrae

Stephane?

Stephane Boissel

Yeah, that's a very good question. So, Biogen will have access to our novel capsid but on a non-exclusive basis, except when it comes to the target that are exclusively license to them.

Maury Raycroft

Got it. And can you say how important those vectors were for the decision to do the deal?

Stephane Boissel

A very important consideration.

Maury Raycroft

Got it. Okay, thank you very much.

Adrian Woolfson

Maury it's one of the things -- Maury, if I may, one of the thing that we have tried to explain why this deal has taken time to come to fruition, is the whole field of both the zinc finger transcription factors and the vector technology and the delivery technology has had to be -- come together and that's why we've waited and taken the necessary time to do the right deal.

Maury Raycroft

Got it. Interesting. Okay, thank you very much and congrats again. I'll hop back in the queue.

Operator

Thank you. And our next question comes from Whitney Ijem with Guggenheim Securities. Your line is open.

Whitney Ijem

Hey guys, thanks for taking the question. And I'll add my congrats, a very exciting deal. I'm going to stick with CNS, the switchover and just ask a question on Huntington's. Curious if there is any updates as it relates to the status of that program or any progress that you can speak to?

Sandy Macrae

That program is now with our friends at Takeda and they will give you updates on it.

Whitney Ijem

Okay, got it. And then moving over to Fabry, probably same question, just curious if there's any color you can give us or anything like that as you kind of continue to screen and enroll patients around when you plan to treat them?

Sandy Macrae

So we will, we will describe the results when the study has been completed and we would expect to do that toward the turn of the year, beginning of next year.

Whitney Ijem

Okay. Can you confirm whether or not you have treated a patient at this point?

Sandy Macrae

We will be recruiting patients throughout 2020.

Whitney Ijem

Got it. Great.

Sandy Macrae

We have not recruited -- to be explicit, we have not recruited a patient. Bettina, would you like to talk to it?

Bettina Cockroft

Absolutely. Thank you. So, we've initiated six sites in the U.S. and actually participated in the initiation of the seventh site in London on Monday this week. So, we're currently screening patients and it's my priority, above all, to ensure the quality of the study by ascertaining that the right patients are included.

And so, we have screened several patients, some of whom had borderline exclusion criteria and who had a screen failed. Indeed, we've had more screen failures than we were expecting at the outset of the trial. But other patients continue to be in the screening phase.

And just as a reminder, screening can take up to two months to complete so we've also introduced protocol amendments that will optimize the inclusion criteria and will allow us to optimize those as well as address the FDA's recent guideline on -- guidance on Fabry disease.

Whitney Ijem

Great, that's helpful, thanks for the update.

Operator

Thank you. [Operator Instructions] Our next question comes from Eric Joseph with J.P. Morgan. Your line is open.

Eric Joseph

Hi, good morning, guys. Thanks for taking the question. I guess maybe just the first question on Fabry, which is whether or not you're experiencing any competition for patients as you're screening here with other trials going on in this space.

And then secondly, on the Biogen deal, I'm just curious to get a sense of what some of the gating items are into initiating IND enabling studies. At the R&D Day, you projected that you'd be in IND for 501 in 2021 and then in 2022 with 502. I'm just trying to get a better understanding of why you thought to do the deal here rather than at IND readiness, where one might argue that you attract a higher value inflection point? Thanks.

Sandy Macrae

So, if I could just say that Fabry is great that there is so many companies interested in it. It's an important medical condition. Our recruitment hasn't been limited by sites interest or investigator interest in our products. In fact, they are very enamored by the preclinical data we've seen. For the reason to do the deal at this stage. Stephane?

Stephane Boissel

Well, I think the question was, as to the timeline, so we have not disclosed updated timelines in partnership with Biogen. What we can say today, Sandy, is that the next step for the tau and the synuclein program is to conduct IND enabling studies. But it's way too early to comment on timing for entering the clinic or market for that matter. I think we will have that in the market with Biogen in due time.

Sandy Macrae

But I think part of Eric's question was why didn't you wait and do at IND. We have had such interested in preclinical candidate. So, I think this is a truly remarkable deal for the stage that the products are at.

Operator

Thank you. And our next question comes from Debjit Chattopadhyay with H.C. Wainwright. Your line is open.

Aaron Welch

Hi guys, good morning. Congrats on the deal and all the progress. This is Aaron on for Debjit. So, can you tell us a -- little bit more color on the kind of data Biogen has seen as far as if there is anything beyond what you've shown at R&D Day? And when might we expect updates on the Alta study? And what kind of follow-up on the patient data might we see. As far as how long the follow-up would be?

Sandy Macrae

Okay. So, let me spread the answers there. So Stephane, do you want to talk about the deal. And then Adrian, if you can talk about the Alta study?

Stephane Boissel

Well, of course, Biogen was on the CDAs so they have seen much more than what we have presented at R&D Day, but we cannot elaborate on that.

Adrian Woolfson

Yeah. And we were in regular contact with Pfizer about the Hemophilia A study. They remain incredibly enthusiastic as to a -- Pfizer will provide the next update and it's probably best if we leave it for them to announce when that happens.

Sandy Macrae

I know they are eager to share the data when it reaches the important time points because they want to make sure that we are all aware of the advantages of this asset.

Aaron Welch

Okay. And that may come at medical conference or publication?

Adrian Woolfson

Pfizer are currently considering a number of different options, but I really think it's probably best to leave it to them to mention that -- the details.

Aaron Welch

Okay, thanks guys, congrats.

Operator

Thank you. And our next question comes from Jim Birchenough with Wells Fargo. Your line is open.

Jim Birchenough

Yeah, hi guys. Let me add my congratulations on the terrific deal and all the progress. Just sticking with neuroscience, do you have a -- is there any data to benchmark the tau reductions and alpha synuclein reduction that you've seen with your approach and some of what Biogen already has in-house in terms of antibody or ASO approaches to those two target?

Sandy Macrae

Good morning. That's a really good question and I'm sure Biogen did that before they did the deal. I think -- I'll ask Adrian to comment in a moment, but I think what Adrian tried to say was that with antibodies or even with RNA modulation, you hit subsets of the genes products and what we achieve is turning off at the source. Adrian?

Adrian Woolfson

Yeah, you've got to remember that the tau forms multiple different misfolded and aberrant species from kind of low molecular weight forms kind of oligomers through to complex high molecular weight misfolded species. And as Sandy said, if you try trying to target this at the protein level, you can never really be certain that you're taking out the pathological misfolded species, right. You can only take out certain molecular weights of misfolded protein.

And similarly, if you try and target at the RNA level there are related problems. And the only way to be absolutely certain that you get rid of all the complex species that are generated when tau misfolds and all the splice variants and so on and so forth is to actually take it out of the level of the DNA and just switch it off.

And that's why we think this -- I mean why Biogen think that this is really probably the way forward in the future and hopefully will lead to a -- really a significant increase in the way -- in the efficiency of treating this disease and hopefully a cure actually.

Jim Birchenough

And then maybe just to follow-up on the question on AAV selection. There was an article in Brain Science this week on neuro-inflammation with AAVs and effects on dorsal root ganglion in spinal cord pathology. When you look at your AAVs that you've developed, can you differentiate at that level and beyond that in terms of tropism for the right neurons. How does it compare to some of the technology that comes out of [UPenn], as an example?

Sandy Macrae

That's a really good question and it's something we've been following carefully and it's something we look at regularly across all cell types in the brain and in the spinal cord and dorsal root ganglion. But we watch that field closely and with all of these conditions we treat with our genomic medicine, it's all about benefit/risk and we are -- we and Biogen are confident that we have the right route forward.

Jim Birchenough

So is that to say, Sandy, that you think you're AAV stand out on that perspective and neuro inflammation specifically as well as tropism?

Sandy Macrae

Let me be quite clear on what I'm saying, so we look carefully for neuro inflammation, both in the CNS and in the peripheral nervous system and particularly after the work that was -- has come out over the past year in the dorsal root ganglion and that would have to be something that our asset, our vector did not cause for this to be a successful medicine and move forward.

Jim Birchenough

Great, that's very clear. Thanks so much, Sandy.

Operator

Thank you. And our next question comes from Gena Wang with Barclays. Your line is open.

Gena Wang

Thank you for taking my questions. I have a few questions regarding the Biogen deals. Just wondering what threshold will trigger the double-digit royalty and also what is the broke-up fee?

Sandy Macrae

Stephane, what can you say?

Stephane Boissel

Well, it's, it's a tiered royalty scheme. So, the more Biogen will be selling the more royalty, or the -- higher the royalty will be for us. That's the way it works. So, we will reach double-digit when we will have crossed certain threshold in sales.

Gena Wang

Okay. So that threshold would be, I think for other deals normally is over $1 billion. Is that in line with other deals? What we've seen in the space?

Sandy Macrae

Nice try.

Gena Wang

Sorry?

Sandy Macrae

I'm afraid we can't disclose that. There is -- it's one of the things that we've agreed not to share.

Gena Wang

Okay. So, and then, what is the break-out fee?

Sandy Macrae

That's another thing that we haven't disclosed. We have no concerns about the break out. This deal is going well.

Gena Wang

Okay. And the last question is the CNS delivery. Just wondering like for each indication where you have to optimize the route of administration and what are the route of administration, you're thinking about?

Adrian Woolfson

Yeah. So, we are going to -- thanks for the question, by the way. We're going to look to pair the optimal delivery solution with each target and indication, which could include natural or engineered AAV serotypes. And at our R&D Day in New York, David Ojala, who is leading our internal AAV engineering efforts using a directed evolutionary approach, showed data on AAV serotypes that we've been developing for use in different neurological diseases and these and our ongoing work on these vectors will be tested for use in our neurological targets with Biogen and may be utilized in the product candidates. So basically, a number of different serotypes and exploring other routes as well.

Gena Wang

Okay, last question. How could the Biogen collaboration accelerate your R&D finding for top programs?

Sandy Macrae

So, as part of any of these deals you agree on a research plan and then the teams will get together over the coming weeks and months and agree on the best way forward together. So, our timings and our guidance to timings remain, but and -- once the teams get together, we will encourage them to move this to patients as quickly as possible.

Gena Wang

Thank you very much. Congratulations again.

Operator

Thank you. And our next question comes from Ritu Baral with Cowen. Your line is open.

Ritu Baral

Good morning, everyone. Thanks for taking the questions. Wanted to ask if there were any carve-outs for indications within the deal for Sangamo? Any particular carve-outs in areas that you guys were most interested in, and can you say anything broadly about where Biogen's focus is going forward for the additional nine candidates. It looks like now, it seems to be in neurodegeneration and neuromuscular. But anything you can say at those points? And then I've got a follow-up on Fabry?

Sandy Macrae

Stephen?

Stephane Boissel

Yeah. Well, it's very important to understand that the deal with Biogen is non-exclusive. There is an exclusivity on 12 targets, including tau and alpha synuclein. But as you know, there are more than one of the relevant neurological target in the brain that cause the field of neurodegeneration, neurodevelopment, neuromuscular or even psychiatry. And so, we reserve the rights to either develop or to partner a very large list of other CNS target.

As far as your second question is concerned, we have not disclosed anything and we are not going to disclose anything about the list of the other targets unless Biogen authorize us to do so in the future when those target will be selected.

Sandy Macrae

And Stephane, it's fair to say though that for tau and the several indications for tau, those all belong to Biogen.

Stephane Boissel

Yes, there is no -- there is no carve out. All indication targeting tau, for example, PSD or Alzheimer will belong to Biogen.

Ritu Baral

Got it. And can you talk to, I guess, the process before selection of the additional nine targets. Like, is there a certain level of preclinical data or in-vitro data you guys will generate and then a decision making time period that Biogen has or is it whatever they want to pick at whatever time, within the five years?

Adrian Woolfson

Sandy, do you want me to answer?

Stephane Boissel

Yeah. So we cannot disclose a lot of details, but of course we -- we need to bring to Biogen a certain preclinical package or certain validation package and the deal is structured in a way that we are, at Sangamo, strongly incentivized to bring those package as rapidly as possible to Biogen.

Ritu Baral

Got it. My next question was actually on some either learnings or more like lessons what not to do. In a competitor Fabry gene therapy program presented at WORLD clinical Phase 1/2 AAV program that showed, I believe it was myocarditis and troponin elevations in Fabry. I was wondering if you guys saw that presentation, had thoughts on if that is a risk to any AAV in Fabry. Is that something that was vector specific and just sort of lessons from that program and dose as you, as you think about your own?

Sandy Macrae

Yes. We saw that data and one that is always careful to comment on safety issues that our friends and other companies have because you don't know all the details and patient safety and lives are important. What I can say though is with our AAV6, we've got a lot of experience now across Hemophilia A and the IVPRP programs and this is something we have not seen in clinic, and we have not seen in any of our preclinical models. So, we are -- we are pleased that we haven't seen this issue, but we will always remain vigilant and hope that free line find a way forward.

Ritu Baral

Is there a rationale, like a medical rationale for why they could see, Fabry patients could see a unique toxicity because of Fabry cardiomyopathy?

Sandy Macrae

So, to the Fabry patients -- as I think I know where you're going with the question. The Fabry patients do you have cardiac disease and it may be that there is a susceptibility there which is why as pleased we are with our safety profile up to now, we will watch with -- as everyone else will, to make sure that our patients are protected and we started the right dose and we look after these patients with all due caution.

Ritu Baral

Has that fed in at all to your -- your careful screening and can you talk to why you have such high screen failures so far?

Sandy Macrae

So, I would refer you to Bettina's answer. Bettina, just -- we refer you to Bettina's answer. The screening problem, sorry the screen challenge is not around the AAV neutralizing antibody. That remains about 30%. It's about understanding the disease and being very careful in choosing the right patients and I think we're all learning about Fabry's disease and which are the right patients and what data and available in their notes and how we can find them and bring them into the study. And we look forward to bringing patients in very soon.

Ritu Baral

Great, thanks for taking the questions.

Operator

Thank you. And our next question comes from Umer Raffat with Evercore ISI. Your line is open.

Mike DiFiore

Hi, this is Mike DiFiore in for Umer. Thanks so much for taking my question and huge congrats on the deal. I have a question that's partially related to a previous question that was asked. Given that Biogen is already developing ASO pipeline assets, specifically in Alzheimer's and Parkinson's. You said in -- not too long ago that this ASO approach may be suboptimal, and that -- it wouldn't be a complete silencing or turning off of genes. So, my question is will Sangamo's zinc finger nuclease approach, could it be complementary or where can these two approaches be used together in treating these diseases? Thank you.

Sandy Macrae

An interesting question. Adrian?

Adrian Woolfson

Yeah, I think, I think this almost certainly will be a role for both approaches. And I think it remains to be seen on how they play together and I'm sure Biogen has very specific ideas about that and probably best to leave it to their development team to, to go into that in more detail.

Sandy Macrae

But to be clear, we hope that our product is the answer and it's unnecessary to dose with anything else.

Mike DiFiore

Got you. Thank you.

Operator

Thank you. And our next question comes from Salim Syed with Mizuho. Your line is open.

Benet Gresley

Hi, good morning. This is Benet Gresley from Salim's team at Mizuho. First of all, congrats on your results and on the deal and thanks for taking the questions. So, just a couple of quick ones for us. First in your studies, for these two candidates ST-501 and 502, did you find any off target gene unregulated? And second in the context of Parkinson's disease, if I'm not wrong, since alpha synuclein has several transcription starting side. Are you targeting certain TSS? Are there other? Thank you.

Sandy Macrae

These are very good questions. Adrian?

Adrian Woolfson

Yeah, I didn't hear the second question. But let me...

Sandy Macrae

Second was about the various start sites or [indiscenrible]?

Adrian Woolfson

Yeah, yeah. So, let me just talk about the first one. So, one of the really important differentiating features about our technology, say for examples, to CRISPR is that that zinc fingers proteins are proteins, right. And that means that they're engineerable in a way that it's just not possible to do with CRISPR. And some of you would have seen, we published a really -- well actually a wonderful paper my colleague at Rebar's team, wrote the paper and they showed how they could reduce off target for nucleases, which of course were not using this situation.

But in the case of nucleases, by tuning the calculated weight of [indiscernible], but the case of transcription factors we had another way of reducing off target and it was through the mutation of arginine-residues, which make non-specific contacts with the negative charge of the DNA helix and by mutating out those residues to glutamines we could reduce off target to virtually zero.

And the data is actually really striking when you see it. I mean this is a phenomenal invention by our team because without these mutations, you get, you know, significantly more off target. So, all reagents now contain these mutations. So, we believe we more or less completely eliminates off target and that's probably make some of the safest reagents of its kind.

And of course, just on another related safety point these a human -- fully human proteins, remember that because both the repressor component and the zinc finger itself is derived from natural recapitulating, natural human gene regulation in the brain, so that's very different.

Sandy Macrae

And Adrian, we would refer them to the patient on -- the paper tau where we show that it's only the tau gene that is repressed. So, from an off-target point of view from tau, we have already published that data. And for synuclein the asset that we would take forward, we would plan to have it with a similar sensitivity.

Adrian Woolfson

And the observation or repression, because we can do both. But in this case repression is intrinsically localized or insulated to the target gene by the cells native machinery that prevents the effect spreading into adjacent genes.

Sandy Macrae

And then your question on synuclein as an interesting, a very technical one and we haven't reviewed which of the start sites that we are targeting, but again it's within the ability of this technology to choose across the starts sites and tile across that, so witch one we're going to do. So, we will -- we will talk more of that in weeks and months to come.

Benet Gresley

Thank you. Thank you very much. That was helpful.

Operator

Thank you. And I'm showing no further questions at this time, I'd like to turn the call back to Sandy Macrae for any closing remarks.

Sandy Macrae

Thank you for joining us today and for your questions. This really is an exciting day for Sangamo and for patients with devastating neurological diseases. With our technology and Biogen's understanding of the science and the medicine and the patients who are out there, we really hope we can do something special. So, we appreciate your support and we look forward to keeping you updated on future developments.

Operator

Ladies and gentlemen this concludes today's conference call. Thank you for participating, you may now disconnect. Everyone have a great day.