Q4 2019 Earnings Call

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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 on our website, sangamo.com, under the investors and media section on the events and presentations page. This call includes forward-looking statements. 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, and Sangamo's collaborations, including their financial and operational impact. Sangamo's Development and Manufacturing Plans and Sangamo's expectations regarding its financial performance. However, actual results may differ substantially from what we discussed today.

Good morning, and welcome to the single most therapeutics teleconference to discuss fourth quarter 2019 financial results. This call is being recorded I'll now pass you over to the coordinator of this event Mcdavid Stilwell Senior Vice President of corporate Communications and Investor Relations.

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 will be referencing slide from our corporate presentation, which can be found at our website Sangamo dot com under the investors in media section in the events and presentations page.

This call and includes forward looking statements. These statements include but are not limited to the timing and scope sank of most economic medicine platform and products the potential for second most product candidates for clinical benefit to patients second most collaborations including their financial and operational impacts.

McDavid Stilwell: 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. However, this is not meant to be considered in isolation or as a substitute for the Comparable Gap Measure.

Second most development and manufacturing plants and sank in those expectations regarding its financial performance.

Actual results may differ substantially from what we discussed today. In addition, these statements are not guarantees of future performance and are subject to certain risks uncertainties assumptions that are detailed in documents 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.

Forward looking statements stated today are made as of this state 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 reconciliation.

Alexander D. Macrae: 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 is available on our website. With me 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, Stéphane Boissel, Head of Corporate Strategy, Adrienne Wolfson, Head of Research and Development, Latina Cockroft, Chief Medical Officer, and Melita Sun-Young, Head of Business Development. On today's call, Sandy will discuss the Biogen collaboration we announced yesterday, Adrian will provide an overview of our ZincFinger 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.

<unk> GAAP to non-GAAP measures discussed on this call are included in today's press release, that's available on our website.

With me this afternoon ER. This morning on this call or several members of the second most senior management team, including Sandy Mcrae, Chief Executive Officer sung Lee Chief Financial Officer, Stefan Blood cell head of corporate strategy, Adrian Watson head of research and development.

Bettina Cockrell, Chief Medical Officer, and Molina Sunday 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 to clinical program update and some will review 2019 financials and now I'd like to turn the call never to Sandy.

Alexander D. Macrae: Thank you, McDavid, and good morning to everyone on the call. We're delighted to be here this morning.

Thank you make David good morning to appeal, Nicole we're delighted to be here. This morning.

Alexander D. Macrae: 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 a $125 million up-front payment and $225 million in proceeds from the purchase by Biogen of approximately 24 million shares of Sangamo 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 first commercial sale and other sales-based milestone payments.

Yesterday afternoon, Sangamo, Biogen announced an ambitious inexpensive collaboration to develop genomic medicines for neurological diseases, including Alzheimer's disease and Parkinson's disease.

The collaboration will leverage sanguine proprietary sink thinker protein or C.S.P. technology to modulate expression of genes involved in your logical diseases, such as tight for Alzheimer's Alpha Synuclein for Parkinson's neuromuscular target a nine authored neurological targets.

Upon closing the transaction sank them overseas $350 million, which is comprised of 125 million dollar upon payment and $225 million in proceeds from the purchase by college and approximately 24 million shares Sangamo store, that's a price of $9 22.

One cents per share.

In addition cycle when we receive up to $2.37 billion, another development regulatory and commercial milestone payments, including up to $925 million in pre approval milestone payments and up to $1.4 billion in first commercial sue another Cmos based milestone payments.

Sanguine will also be eligible to receive tiered high single digit to some teed up double digit royalties from biogen on potential <unk> commercial see whose products are rising from the cooperation.

Alexander D. Macrae: 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 Zincfinger 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.

The magnitude at this collaboration reflects the truth all your purchasing finger talk from technology.

Her experience and passionate scientists have worked optimized for therapeutic applications and the immense promise of genomic medicine in your signs we're truly through to be collaboration with Biogen, where pioneers in neuroscience drug development and committed to the development of individual medicines in this field.

Sangamon by June agree that through school urgent unmet patient need and the potential for medical breakthroughs in the future numerous times in the case about same or some Parkinson's. The current standard of care treatments are symptom focus under their new approved treatments to modify were slow the relentless progression of these devastating.

Your agenda diseases.

Alexander D. Macrae: That's why the promise of genomic medicine to provide a one-time treatment that addresses the underlying cause of disease at a DNA level is so powerful. Genomic medicine in the field of neuroscience offers the hope of potentially altering the natural history of a disease for patients. At Sangamo, we feel a responsibility and a sense of urgency to translate our promising science 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.

That's why the promise of genomic medicine to provide a one time treatment that addresses the underlying cause of disease at a de any life. It was soon however for.

But you know we've mentioned in the field of newer signs offers hope of potentially altering the natural history open to cease for patients.

At single, we feel the responsibility in a sense of urgency to actually start promising signs into genomic made since it can enter the clinic.

And that's one of your structured used to simultaneously to build or wouldn't proprietary product candidate pipeline.

The partner when we need access to exceptional therapeutic area expertise or the financial resources to rapidly move or programs forward in the clinic.

We feel that the combination of are engineered zinc finger proteins, biogens unmatched neuroscience expertise capability and infrastructure along with our shared commitment to bring innovative new neurological medicines to patients establishes the foundation for a robust and compelling partnership.

We are excited to Biogen those books this partner on a strategic shareholder we look forward to working with them to advance these important programs.

Alexander D. Macrae: We are excited to have Biogen as both a partner and a strategic shareholder, and we look forward to working with them to advance these important programs. As Biogen has said, they are 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. Collaboration 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 have 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.

Despite genocide, they're equally excited to work with <unk> to treat challenging neurological diseases global significance are committed to quickly progressing programs forward to I'd applications.

A combination with Biogen is an.

Excellent examples with our research productivity can translate into value for shareholders.

Frequency spoken about the leasing potentially for CFP platform a technology. We believed that we can engineer to address virtually any genomic target, which is able to generate an expensive pipeline.

Collaborations such as this one that enabled us to actually the potential the technology in partnership with therapeutic area liters injuries significant cash to fund or new an ongoing R&D activities.

Alexander D. Macrae: To date, Sangamo has brought in approximately $700 million through license fees, milestones, and equity from our partnerships. In terms of future opportunities, 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 take 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 the 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 and hundreds of additional potential neurological disease targets.

Did you signed them was brought in approximately $700 million food licensees milestones an equity from or partnerships in terms of future opportunities and additions. In addition to royalties on net product sales.

Sangamo could docs, who earn up to $6.34 billion in potential milestone payments from our partnerships cumulative.

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We're diligent an intentional in the choice of or partnerships until it was the necessary time to find the right partner and to try to negotiate specific of rights that we arrived licensing.

Today, we have entered into strategic cooperation starting with three targets with an option for nine additional neurological targets to be selected by region.

Beyond those 12, two targets, we retained the rights to use of our technology and 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 shareholders.

Alexander D. Macrae: 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 will be especially important as Sangamo enters a second wave of development, applying our genomic medicine technologies to disease areas with large patient populations and great unmet medical needs. In addition to starting our journey with Pygen, this quarter also marked an important milestone for Sangamo as we became a Phase 3 company. We transferred the IND for SB525 haemophilia 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 of bringing our genomic medicines to patients.

These partnerships, we especially important single winters, a second weve with development applying our genomic medicine technologies to disease areas with large patient populations greed unmet medical need.

In addition to start to your Jordan with production. This quarter also marked an important milestone for cycle as we became a piece three company.

We transferred the R&D for SP five to five he must really a gene therapy towards development partner Pfizer, We're planning to initiate a phase three registrational trial later this year.

This brings us one step closer toward mission to bring our generic medicines to patients.

Finally, before I turn the call over to my colleagues I would like to congratulate teams that cycle for the courage, they've taken to true beliefs, and this new era Oh.

Alexander D. Macrae: Finally, before I turn the call over to my colleagues, I would like to congratulate the teams at Sangamo for the courage that it takes to trailblaze in this new era of new areas of genomic science and medicine and for the discipline and hard work that has been necessary to become a phase-free company and to execute an unprecedented neurological disease collaboration. I'd like to say special thanks to Stéphane 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. Thank you, Sandy.

A new area of genetic sciences, and medicine and for the discipline and hard work that's been necessary to become a these three company and to execute an unprecedented you recall neurological disease collaboration.

I'd like to see special thanks to stay somewhere so our head of corporate strategy and our teams and corporate development business development and research whose leadership in focus were instrumental in helping <unk> urge enter into this important partnership.

With that I'll turn the cold for to Adrian.

Thank you Sandy.

Operator: Yesterday afternoon, we were delighted to announce our new collaboration with Biogen to develop Sangamo's proprietary engineered ThinkFinger protein technology into genomic medicines for neurological diseases of global significance. The ability to switch genes on and off in the brain precisely and with great specificity is a really exciting new development in the application of genomic medicines in neuroscience.

Yesterday afternoon, we were delighted to announce on you collaboration with Biogen to develop sanctimonious proprietary engineered things think approaching technology into genetic medicines for neurological diseases the Bible significance.

The ability to switch jeans on and to switch genes off in the brain precisely and with great specificity.

These are really exciting new developments in the application of generic genetic medicines in neuroscience.

Adrian: The first product candidates in the collaboration, ST501 targeting tau, and ST502, which targets alpha-synuclein, leverage Sangamo's pioneering genome regulation technology, ThinkFinger Protein Transcription Factors (ZFPTFs), which are currently delivered using adeno-associated viruses (AAVs), and function at the DNA level, 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, genome-wide specificity, and long-term tolerability of ThinkFinger protein 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 area, including for single gene tunable panallelic regulation of targets such as tau or alpha-synuclein or allyl selective repression, as is the case with our Huntington's and ALS programs.

The first product candidates in the collaboration.

He 501 targeting towel and that's T 502, which targets Alfredsson Nixon leverage sangamo pioneering genome regulation technology same thing approaching transcription factors. The S.P.T.S., what's the current needs delivered using I didn't know associated forest is a.

Ladies and.

And function at the DNA level selectively repressed well right today's expression specific genes to achieved that decides therapeutic effect.

Last year Sangamo published a manuscript in nature medicine detailing the high selectivity genome wide specificity and the long time, Tolerability axing finger protein T. S. In preclinical models of Huntingtons disease.

Provided proof of concept to this technology.

The P.T.S. can be engineered for a wide range of applications within the neurological disease area space.

Including the single gene tunable kinda realec regulation of targets such as to how we're alpha synuclein.

Well rautio selective repression.

As the case with all Huntingtons, an L.S. programs.

Adrian: This technology also has many potential applications beyond neuro, as it allows gene expression to be tuned to therapeutic levels in any cell type. Sangamo's differentiated CF-PTF technology provides 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's an accumulation of toxic, misfolded proteins in neurons. And targeting a 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.

It's technology also has many potential applications beyond your eye signs as it allows gene expression to be choosing to therapeutic levels in any cell site.

Thank you most differentiated C.S.P.T.F. technology provides several important benefits over other therapeutic strategies to the current younger investigation.

In the case, if there is a generous it diseases such as Alzheimer's and Parkinson's for example, this an accumulation of toxic misfolded proteins in your runs.

And targeting the treatment. So all the different forms of these proteins is incredibly difficult.

There's also challenging to target orange.

It's the separable several copies of these molecules and they come in multiple forms.

Adrian: In contrast, however, by targeting the disease upstream of both the protein and the RNA complexity using ZFPTS, we were able to address the key drivers of the disease at the source by repressing their expression at the DNA level. Furthermore, the prospect 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 neurons has been shown to provide benefit in animal models of tauopathy. Similarly, misfolding and aggregation of alpha-synuclein have been shown to play a central role in the cellular deficits associated with Parkinson's disease.

In contrast, however by targeting disease upstream the first the protein and the ornate complexity using C.S.P.T.S., we were able to address the key drivers of the disease at the source.

Repressing their expression the DNA level.

Furthermore, the prospect of a onetime administration. The navy there can restrict the expression, let's see if P.T.S. specific cell populations as many important essentially advantages over other therapeutic modalities. The currently on the clinical investigation.

In the case about sign this disease another telepathy, the progressive accumulation of toxic how pricing in the brain its links in your own all those clinical symptoms.

Reducing the total amount of towel expressed within your rights has been shown to provide benefit in animal models of telepathy.

Similarly, there's folding an aggregation of alpha Synuclein, it's been shown to play a central role in this study that deficits associated with Parkinson's disease.

Adrian: Consequently, reducing the expression of tau or alpha-synuclein in the brain may have the potential to slow or even halt the progression of Alzheimer's disease and Parkinson's disease, respectively. The current marketed treatments target the symptoms of these diseases, and it 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 for the CNS. Preclinical studies have demonstrated the ability of AV vectors to efficiently deliver CFPTFs that are targeted to Tau, ST501, or alpha-synuclein-targeted ST502, and that result in highly specific, potent, and tunable repression of Tau and of alpha-synucle Indeed, the preclinical data presented by Sangamo last year demonstrated a significant reduction of tau expression in the non-human primate brain following administration of targeted ZFPTF.

Consequently, reducing the expression of town or Alpha Synuclein in the brain may have to potential to slow or even to halt the progression of Alzheimer's disease, and Parkinson's disease, respectively.

The current marketed treatment talk at the symptoms at these diseases and it would clearly be very compelling so have a treatment targets disease progression, but additionally, also slow as well complete your Russ disease pathology.

I'm really immensely excited about this collaboration because it unlocks a whole new area madsen into the CNS.

Preclinical studies have demonstrated the ability of baby vaccines to efficiently deliver C.S.P.T.F. the targeted to towel S. T 501, or alpha Synuclein targeted SP five zero too.

The result in highly specific potent and tunable repression apparel and if alpha synuclein.

Indeed, the preclinical data presented by thanking my last year demonstrated significant reduction it's how expression in the non human primate grain pulling administration of targeted C. F. Pts.

Adrian: 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 systems. 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 AV delivery vectors and ZFPTFs that target therapeutically relevant genes. Following this pre-clinical 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, SB525, into a phase three program with Pfizer and securing the necessary regulatory approvals to advance additional gene and cell therapy programs into phase one. Two clinical trials throughout the year, starting with sp525 haemophilia ray gene therapy. In addition to the recent transfer of the program to Pfizer, we were pleased with The data showed that SB-525 was generally well-tolerated and suggests the potential for sustained factor VIII levels following treatment. We will continue to observe durability as the follow-up data accumulates.

We also presented preclinical data last December it's our R&D day in New York City.

So to more than half the C.S.P.T.S. tested reduced the total alpha synuclein levels by greater than 50% in ex vivo cell culture system.

We have very excited to out with Biogen to further develop these assets that's progressing so I envy, enabling studies.

Under the terms of all collaboration with Biogen Sangamo will take the lead on early for such activities ended the developments of proprietary neurological Avi delivery factors and C.S.P.T.F. the target therapeutically relevant genes.

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

Turning now to some kinda cooperates. We ended 2019 on a strong notes progressing or lead asset SP five to five instead of phase three program with Pfizer and securing the necessary regulatory approvals to advance additional gene and cell therapy programs into phase ones, who chemicals.

Charles throughout the year.

Starting with SP five to five hemophilia Ray gene therapy.

In addition to the recent transfer good programs to Pfizer.

Pleased with the phase once he data was presented at the Ash annual meeting in December.

The data showed the SP five to five was generally well tolerated and suggest the potential for sustained facts rate levels following treatment.

We will continue to upsize the durability as a follow up data accumulate.

Adrian: Moving now to our follow-on and wholly owned gene therapy S290 for Fabry disease. We're currently screening patients in the STAR clinical trial, which currently has six sites open in the U.S. The first European site was initiated in London this week.

Moving now to a follow on and only young gene therapy as to nine zero for Fabry disease.

We currently screening patients install clinical trial, which currently has six sites open in the U.S.

The first European sites was initiated in London. This week.

Adrian: ST920 received orphan drug designation from the European Medicines Agency in January. At ASH last year, we presented preliminary information from the Phase 1-2 Thalase study assessing ST400, an ex vivo gene-edited cell therapy, in patients with transfusion-dependent beta thalassemia, in partnership with Phenothi. 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 Pre-CANS 1 trial evaluating BIVV003, a 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 ST400, but the mobilization regimen of the patient's cells differs. Plerixifor is used in combination with GCSF and beta-thalassemia, as compared with Plerixifor alone for sickle cell disease, as GCSF is contraindicated in this patient population.

S.T. nine to zero received orphan drug designation from the European Medicines Agency in January.

That's last year, we presented preliminary information from the phase one to fall a study assessing S. T 400, and 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 at the treatment.

Also in partnership with Sanofi. The first patient was dosed in the phase one two pre Ken's one trial evaluating B.I.D.V. 003 or related ex vivo gene edited cell therapy for the treatment of sickle cell disease, who is sangamo received the 7.5.

Billion dollar most and payments.

Yeah, Hi V easy rosy rate three uses an identical things finger nucleases mediated editing and manufacturing process to actually 400, but the mobilization regimen the patients cells differs.

For example is used in combination with G CSF and piece of palettes seem yet as compared with three rigs to fool alone for sickle cell disease is G. CSF is contra indicated in this patient population.

Moving on now 12 first in human car T. Reg cells therapy, CX 200, and we're happy to say that we recently received a number of regulatory approvals, including clinical trial application authorization in the UK.

Adrian: 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 I-II Steadfast clinical study in HLA-A2 mismatched 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 a 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 development 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 Seung for an overview of the financial results. Seung

For the phase one two steadfast clinical study in H. like eight to mismatched kidney transplantation we.

We will continue to work closely with our own quality Collaborates a tight as they had fonts kite 037, and allogeneic anti Cdnineteen car T therapy into a clinical trial this year.

Finally, I would like to mention that we were pleased to see the FDA guidance on gene therapy manufacturing clinical developments of products that was published in January.

It is certainly immensely encouraging but the F.D.A. recognizes the promise of gene therapy, and it's creating regulatory pathways for this new treatment modality.

We very much look forward to continuing our interactions with the FDA as we thought that's about it and progress our genetic medicine pipeline.

I will now turn it over to some for an overview the financial results some.

Thank you Adrian and good morning, everyone I first began with the fourth quarter results.

Sung Lee: Thank you, Adrienne, 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,

We reported consolidated net income of $4.6 million or four cents per share compared to a net loss of $18.7 million or 18 cents 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 dollar milestones achieved for us the five to five or hemophilia a candidate partnered with Pfizer.

And a 7.5 million dollar milestones achieved for sickle cell disease candidate partnered with Sanofi.

Total operating expenses were 53 point $53.4 million compared to $47.6 million for the same period in 2018.

Turning to the full year 2019 results.

Sung Lee: 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 revenue 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 the 2020 four-year guidance, we anticipate operating expenses, excluding stock compensation, to be in the range of $245 million to $260 million.

Consolidated net loss was $95.2 million or 85 cents per share compared to a net loss of $68.3 million were 70 cents 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 <unk> Yeah.

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 Companys overall head count growth in facilities expansion to support the advancement of San Dimas 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 2024 your guidance.

We anticipate operating expenses, excluding stock compensation to be in the range of 245 million to $260 million.

Sung Lee: 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. Thank you so much.

This range reflects investments to support our new collaboration with Biogen continued progress towards GMP manufacturing capability and progression of our clinical programs.

And finally, a sandy mentioned earlier, we're excited about the potential of the partnership with Biogen <unk>.

Collaboration has been approved by the boards of directors, both company and is subject to customary closing conditions, including the expiration of of the applicable waiting period under the Hart Scott Rodino Anti trust improvements active 1976.

This transaction is anticipated to close into 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 partner programs potentially through Pfizer's first BLE filing of SP five to five for hemophilia a and beyond.

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

Thank you some.

Alexander D. Macrae: This is an exciting day at Sango, and I'm sure you all have lots of questions, so let's just get straight to it. Operator.

This is an exciting data cycle and I'm sure you'll have lots of questions. So, let's just get straight to operator.

Thank you.

Operator: Thank you. To ask a question, you need to press star 1 on your telephone. To withdraw your question, press the pound key. Again, that's star 1. To ask a question... Our first question comes from Maury Raycroft with Jefferies.

I ask a question you need to press star one on your telephone to withdraw your question press the pound key again, that's star one to ask a question.

Our first question comes from.

Maury Raycroft with Jefferies. Your line is open.

Maurice Thomas Raycroft: Hi everyone, good morning, and congrats on that update. It seems like a great deal.

Hi, everyone. Good morning, and congrats on that update on seems like a great deal to start I'm wondering if you could say how far along that the neuromuscular program is.

Maurice Thomas Raycroft: To start...

Maurice Thomas Raycroft: To start, I'm wondering if you can say how far along the neuromuscular program is.

Maury. Thank thank you for your question.

Alexander D. 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.

We haven't said anything about this neuromuscular program and it's it's and further unnamed target by Biogen, but it's it's an exciting example look their confidence in our technology.

Got it and and then for the nine on selected targets. If Biogen does not like those by 2025, what happens and then for the nine targets can you talk about how long it could take you get it therapy, you're ready for a target and just generally how resources will be used for these targets.

Maurice Thomas Raycroft: 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 and just generally how resources will be used for these targets?

Let me pass that went on to Stefan.

Stéphane Boissel: Let me pass that one on to Stefan.

Hi, Mike So for the first part of your question if those Doggett Donna selected by de Tam of the five year collaboration time.

Stéphane Boissel: Hi Maurice. So for the first part of your question, if those targets are not selected by the term of the five-year collaboration time, we would be freed from the exclusivity under the biogenic agreement. And for the second part of your question, could you please repeat it, please?

We would be freed from the excludes EG under the biology and getting them on photos sit on top of your question can you. Please you did please.

Sure just wondering for the nine targets if you could talk about how long it takes two to get wanted them Brady.

Maurice Thomas 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, and a program ready for it, and just generally how resources will be used for these different therapies.

Actually you know a product program ready for it and just generally how resources will be used for for these different therapies.

But it's very valuable I think you'd we did put on a target Beth take it bases, but we probably need between nine to 18 months and about the I get babies and that will we we view of course conducted by bites functional.

Stéphane Boissel: Well, it's very viable. I think it will depend on the target-per-target basis, but we probably need between nine to 18 months on a per-target basis, and that work will, of course, be conducted by Sangamo.

But what's been I really pleasing, but this platform is I do affect just the team has been.

Targeting new new jeans, and you saw the R&D day that we should that evidence of bodes.

Alzheimer's, which would take for Alzheimer's, which been studying for a point, we I didn't sign you clean which was really only done in a very short and periods of time, and then probably own disease, which is not part of of the deal. That's work they do only being going on for I don't three just six months. So we're very pleased to how quickly in effect.

Alexander D. Macrae: But what's been really pleasing about this platform is how effective the team has been at and how successfully they are able to create assets for new targets, and I think that was one of the things that gave Biogen great confidence that we could succeed with their list.

Typically and successfully the team are able to.

Create assets for new targets and I think that was one of the things that give by June great confidence that week, we could succeed with their their list.

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

Got it and.

And then if you can talk about rights year novel, CNS Avi vectors, I guess, there's biogen have any unique or exclusive rights to those factors.

Stéphane 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 targets that are exclusively licensed to them. Got it.

Uh huh.

Yeah, that's a very good questions. So.

Biogen will have access to all Nova capsid, but on the nonexclusive basis, except when it comes to the target that exclude the license to them.

Got it and can you say how important those factors were.

Maurice Thomas Raycroft: And can you say how important those vectors were for the decision to do the deal?

For the decision to do the deal.

A very important consideration.

Alexander D. Macrae: A very important consideration.

Got it okay. Thank you very much more Lori laureates one of the thing Maria if I may is one of the things that we have tried to explain point. This deal has taken time to come to fruition is the whole futile both the.

Maurice Thomas Raycroft: Okay, thank you very much.

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

I think finger transcription factors and the vector technology on the delivery technology has has had to be come together and that's why we've wasted and taking the necessary time to do the right deal.

Got it interesting okay. Thank you very much in that congrats again.

Alexander D. Macrae: Got it. Interesting. Okay. Thank you very much and congrats again.

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

Thank you and our next question comes from.

With Guggenheim Securities. Your line is open.

Whitney Idem: Hey guys, thanks for taking the question and I'll add my congratulations on a very exciting deal. I'm going to stick with CNS but switch over and just ask a question on Huntington's. Curious if there are any updates as it relates to the status of that program or any progress that you can speak to.

Hey, guys. Thanks for taking the question and I'll add my congrats everything deal I'm going to stick with CNS such over and just ask a question on Huntingtons curious if there's any update on as it relates to the status of that program or or any progress that you can speak too.

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

Alexander D. Macrae: That program is now with our friends at Takeda, and they will give you updates on it.

Whitney Idem: Okay, got it. And then moving over to Fabriry, probably the 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.

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

So we will we will describe the results when the study has been completed and we would expect to do that towards the turn of the you're beginning of next year.

Alexander D. Macrae: So we will describe the results when the study has been completed, and we would expect to do that towards the turn of the year or beginning of next year.

Okay can you confirm whether or not you have treating the patient at this point.

Whitney Idem: Okay, can you confirm whether or not you have treated a patient at this point?

We will be recruiting patients through <unk>.

Alexander D. Macrae: We will be recruiting patients throughout 2020.

Bettina M. Cockroft: To be explicit, we have not recruited a patient. Bettina, would you like to talk to us? Absolutely.

Twentytwenty.

Got it okay great.

To be explicit we have not recruited a patient bettina would you like to talk to physically.

Bettina M. Cockroft: Thank you. So we've initiated six sites in the U.S. and actually participated in the opening 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 were thus screened 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 guidance on guidance on Fabry disease. Great, that's helpful. Thanks for the update.

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 right patients are included.

And so we have screen several patients some of whom hod borderline exclusion criteria and who are those screen failed.

Indeed, we've had more screen failures than we were expecting at the outset up the trial, but other patients continue to be in the screening phase and just as a reminder, screening can take up to two month to complete.

So we both synergies protocol amendments that will optimize the inclusion criteria and will allow us to optimize those as well as address the FDA suites guideline on guidance something fabry disease.

Great. That's helpful. Thanks to the update.

Thank you and we'd like to remind you to please limit yourself to two questions and then hop back in the Q.

Eric Joseph: Thank you. And we would like to remind you to please ask, limit yourself to two questions, and then hop back in the queue. Our next question comes from Eric Joseph with JP Morgan. Your line is open.

Next question comes from Eric Joseph with JP Morgan Your line is open.

Eric Joseph: Good morning, guys. Thanks for taking the questions.

Hi, Good morning, guys. Thanks for taking the question.

Eric Joseph: I guess maybe just the first question on FabRAse, 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, on the Biogen deal, I'm just curious to get a sense of what some of the gating items are for initiating IND-enabling studies. With the R&D day, you projected that you'd be in IND for 5.01 in 2021 and then in 2022 with 5.02. 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.

I guess, maybe just the first question on Padres, which is whether or not youre experiencing any competition for patients as your screening here with other trials going on in this space and then secondly on the Biogen deal I'm just.

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 an eye Indy for fiber one in 2021 in that in a 2022, if I go to I'm, just trying to get a better stand and understanding of why you thought to be the deal here rather than at I'd, rather readiness, where you might argue that you.

I tried to higher value inflection point thanks.

So if I could just say, but fabry, it's great that there's so many companies interested in it it's an important medical condition.

Alexander D. Macrae: So, if I could just say about Fabry, it's great that there are 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 product. In fact, they are very enamored by the preclinical data we've seen. What is the reason to do the deal at this stage, Stefan?

Our.

Our recruitment hasn't been limited body sites and trust or investigator interest in their products and thought they are very enamored by the the preclinical data. We've we've seen for that reason to do the deal at this stage Stefan.

Well.

Stéphane Boissel: Well, I think the question was more 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 in the CynicClean 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 update the market with Biogen.

Are you seem to question wasn't as to the timeline.

So we have not disclose a day to timelines in partnership we buy Eugene what we can said today Sandy that the next step for the tell on Synuclein plug armies to come to I, India and they've been studies.

But it's way too early to comment on timing for and talking to its unique all knocking for that matter I think we would have that the market we buy a ginny.

Stéphane Boissel: And I think part of Eric's question was, why didn't you wait and do it at IND? We have had such interest in pre-clinical candidates. I think this is a truly remarkable deal for the stage that the products are at.

But I think part Barrys question was why Didnt, you wait and due to our indeed, we have had such interested in preclinical candidates I think this is.

Truly remarkable due for the stage the products are right.

Thank you and our next question comes from Debjit.

Eric Joseph: Thank you. And our next question comes from DipDip Chattopadhyay with H.C. Wainwright. Your line is open.

Potty with H.C. Wainwright your line is open.

DipDip Chattopadhyay: Hi guys, good morning. Congratulations on the deal and all the progress. This is Aaron from DevJet.

Hi, guys. Good morning, Congrats on the deal and all the progress this is airing on ER that's it.

DipDip Chattopadhyay: So can you tell us a little bit more color on the kind of data Biogen has seen as far as if there's anything beyond what you've shown at the R&D day? And when might we expect updates on the Ulta study? And what kind of follow-up on the patient data might be, as far as how long the follow-up would be?

So can you tell us.

Little bit more color on the kind of data Biogen has seen as far as if theres anything beyond what youve shown at R&D day.

And when might we expect updates on the office study and what kind of follow up on the patient data or might we see.

Well it is as far as to how long would be.

Okay. So let me spread the the answers the suit Stephens you want to talk with you and they need tree and if you can talk a bit to study.

DipDip Chattopadhyay: Okay, so let me spread the answers on this. So, Stefan, do you want to talk about the deal? And then Adrienne, would you like to talk about the ALTA study?

Stéphane Boissel: Well, of course, Biogen was under CDA, so they saw much more than what we presented at R&D Day.

Well of course, Biogen wasn't they'll see da's. So they have seen much mode and what we up by something that Andy day, but we cannot.

Stéphane Boissel: Yeah. OK.

Right on that.

Yes, and we you know we were in regular contact with Pfizer about hemophilia. A study you know they remain incredibly enthusiastic has two way.

DipDip Chattopadhyay: And this is really a study, you know; they remain incredibly enthusiastic, as do we. I think Pfizer will provide the next update, and it's probably best if we leave it for them to announce.

You fight Pfizer will provide the next stop Jason it's probably best if we need it for them to announce when that happens.

DipDip Chattopadhyay: Oh, no; I was just asking if you were eager.

Oh no.

Uh huh.

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

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

DipDip Chattopadhyay: Okay, and that might come up at a medical conference or publication.

Okay and that might come at.

Medical costs and their application.

Feis recurrent me a it considering a number of different options, but I really think it's probably best to leave it to them too she mentioned that.

DipDip Chattopadhyay: Pfizer is currently considering a number of different options, but I really think it's probably best to leave it to them to mention the details.

The details.

Okay. Thanks, guys congrats.

DipDip Chattopadhyay: Okay. Thanks, guys. Congratulations.

Thank you and our next question comes from Jim touched off with Wells Fargo. Your line is open.

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

Jim Birchnoff: Hi guys, let me add my congratulations and all the progress. Just sticking with neuroscience. Do you have any data to benchmark the tau reductions and alpha-synuclein reductions 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 targets?

Hi, guys, let me add my congratulations on the terrific deal and all the progress just sticking with neuroscience.

Yes, it's or any data to benchmark, how reductions and alpha synuclein reductions that you've seen with your approach and some of what Biogen already has in house in terms of anti body or so approaches to those two targets.

Alexander D. Macrae: Good morning. That's a really good question. And I'm sure Biden did that before they did the deal, um, The, 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 gene's products, and what we achieve is turning it off at the source.

Good morning, that's that's a really good question and I'm sure Biogen did before they did the deal.

The I think.

Well I'll ask agent to comment in a movement, but I think what Adrian tried to see was that with anti bodies or even with R&D modulation you hit subsets of the genes products and what we achieved is turning off at the source Adrian Yeah, you you've got to remember the.

Adrian: Adrian?

Adrian: Yeah, you've got to remember that tau forms multiple different misfolded aberrant species, from low molecular weight forms, oligomers, through to complex high molecular weight misfolded species. And as Sandy said, if you try and 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, you know, molecular weights of misfolded proteins. And similarly, if you try and target it 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 DNA and just switch it off. And that's why we think this and why Biogen think that this is really probably the way forward in the future and, hopefully, will lead to a really significant increase in the way in which we treat this disease and, hopefully, a cure.

The tile forms multiple different misfolded upper and species from you know kind of.

Low molecular weight forms kind of older come as three too complex high molecular weight and Misfolded Spcs unassigned. He said you know you trying to target you said the protein level.

You can never really besides and taking out the pathological misfolded species right you can any takeout.

Sutton.

You know molecular weight took misfolded protein and similarly, you could try and talking to the ordinary level, the REIT related problems and the only way to be absolutely certain that you get rid of all the complex. Some space. He said it generates it went wouldn't how misfolds an older splice variants and so on and so forth.

To actually take it out level, if the DNA and just switch it often and that's why we think there's some white biogen.

Thank goodness is really probably the way forward in the future and hopefully will lead to a.

Really significant increase in the way.

The efficiency of treating this disease and I feel secure actually.

Jim Birchnoff: And then maybe just to follow up on the question on AAV selection, there was an article in Brain Science this week on neuroinflammation with AAVs and effects on dorsal root ganglion and spinal cord pathology. When you look at your AAVs that you've..., www.kenhub.com

And then maybe just a follow up on on the question on 80 selection there was.

An article on brain fine this week on neuro information with a these.

Excellent dorsal route ganglion in spinal cord pathology when you look at your ratings, but you are the.

Develop can you differentiate at that level and and beyond that in terms of tropism for for the right neurons, how does it compared to some of the technology that comes out of Japan as an example.

That's a really good question and it's something we've been following carefully and it's something we lucado regularly across all cell types in the brain and in the spinal cord and Dolce <unk> Gabbana Liam.

Alexander D. 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 and Biogen are confident that we have the right route forward.

But we we watched fuel closely and with all of these.

Conditions, we treat with our genomic medicine is all of the benefit risk and we are we in Biogen are confident that we have the right route forward.

So that to say Sandy that you think your Avi stand out on on that perspective, and no inflation, specifically as well as tropism.

Jim Birchnoff: So is that to say, Sandy, that you think your AAVs stand out from the perspective of neuroinflammation specifically, as well as tropism?

Well I, let me, let me be I'm quite clear what I'm, saying is that we look carefully for your inflammation, both in the CNS and peripheral nervous system and particularly after the the work that was the has come over the past year in the dorsal route ganglion and that would have to be something.

Alexander D. Macrae: Let me be quite clear about what I'm saying is that we look carefully for neuroinflammation both in the CNS and in the peripheral nervous system, and particularly after the work that has come out over the past year in the dorsal root ganglion, and that would have to be something that our vector did not cause for this to be a successful medicine and movement.

[music].

<unk> acid or vector did not cause for this to be successful medicine and move forward.

Jim Birchnoff: Great, that's very clear. Thanks so much.

Great that's very clear thanks, so much study.

Huidong Wang: Thank you. And our next question comes from Jenna Wang with. Barclays, your line is open.

Thank you and our next question comes from Gena Wang with.

Barclays. Your line is open.

Huidong Wang: Thank you for taking my questions. I have a few questions regarding the vouching deals. Thresher will trigger the double-digit royalty. And also, what is the broke up theme?

Thank you for taking my question I have a few questions regarding the Biogen deals.

Just wondering what.

[laughter], Russia were treated like a double digit of loyalty.

And also what did I feel comfortable Stefan can you say.

Stefan: Stefan, what can you say?

Stefan: Well, it's a tiered royalty scheme, so the more Biogen sells, the more royalties, or the higher the royalty will be for us. That's the way it works. So we will reach double digits when we have crossed a certain threshold in sales.

Well it's a.

He why a de schemes so the Mo bio gene we'd be selling the more Oh Gee I, otherwise you would be for us.

That's the weight work, so we will have each.

WG when we love cause it felt on the threshold in sales.

Huidong Wang: Okay, so that threshold would be, I think for other deals, normally it's over a billion. Is that in line with other deals? What are we seeing in the space?

Okay. So that's threshold would be I think <unk> other deals normally the overall is that in line with other deals where we've seen in the space.

Huidong Wang: Nice tie.

Hi.

Sorry.

Stefan: I'm afraid we can't disclose that. There's...

I'm afraid we can't disclose side, there's there's okay. It's just kind of thing so we've agreed not to sure okay.

Huidong Wang: Okay.

Stefan: It's one of the things that we've agreed not to share. Okay?

Huidong Wang: Okay, so, and then what is the breakout fee?

Okay. So I mean, what is the breakout fee.

Stefan: That's another thing that we haven't disclosed. We have no concerns about a breakup. This deal is going well.

That's another thing that we haven't disclosed we have no concerns supposed to break up the this deal is going well.

Huidong Wang: Okay. And the last question is CNS delivery. Just wondering, like, for each indication, will you have to optimize the route of administration? And what are the modes of administration you are thinking about?

Okay and the last question is that the CNS delivery I just wondering late for each indication when you have to optimize the route of administration and what are the route of administration you are thinking about.

Huidong Wang: Yes, so we're 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 spherotypes. And at our R&D day in New York, David Ajala, who's leading our internal AAV engineering efforts using a directed evolutionary approach, presented data on A-B spherotypes that we [inaudible]

Yeah, so were going to where I think so the question by the way we can I look to pass the optimal delivery solution with each target an indication.

Which could include not true or engineered Avi subtypes, and a door R&D then you'll come they put a job.

He is leading our internal Avi engineering efforts using Oh, it's on a direct to evolutionary approach show dates are on a b separate sites that we've been developing.

For use in different neurological diseases and piece in our ongoing work in these factors would be tested for use in all neurological targets with Biogen and maybe utilized in the product candidates. So basically a.

Adrian: and others

Adrian: The number of different

Adrian: and exploring other routes as well.

A number of different stereotypes and exploring other routes as well.

Huidong Wang: Okay, last question. How could Belgian collaboration accelerate your R&D planning for TAR programs?

Okay last question, how could the allergan collaborations like salary youre defining foot tall programs.

Alexander D. 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 on timings remain, but once the teams get together, we will encourage them to move this to patients as quickly as possible.

So a surplus parts if 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 thought and once the teams get together we book.

Encourage them to moves this to patients as quickly as possible.

Huidong Wang: Thank you very much. Congratulations again.

Thank you very much congratulation again.

Anvita Gupta: Thank you. And our next question comes from Ritu Bharel with Cowan. Your line is open.

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

Anvita Gupta: Good morning, everyone. Thanks for taking the questions. I 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 on those points, and then I've got a follow-up on Fabry.

Good morning, everyone. Thanks for taking the question.

There were any carved out for indications we ended deal for Sangamo.

Any any any particular carve out in areas that you guys were most interested in and can you say anything broadly about where.

By agent focus is going forward for any additional nine candidates. It looks like now it seems to be in your and your generation neuromuscular.

Thank you can say to this point and they've got a follow on salary.

Stefan: Stefan

Seth.

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

Yeah, well, it's very important you understand that the the deal with Biogen ease nonexclusive. They use an exclusivity on 12, doggett, including tell us anything but as you know there are more than.

One of the sort of and know what did you could I get into paying that caused the field of Neurodegeneration youre they've left money on these you know I've been cycle.

And so we have his day job.

Hi, just you they'd love to stop now they labs east of although you know CNS target.

As you sit on a question on these concepts, we have not disclose anything and we are not going to disclose anything about the least.

The Oh, they'll targets unless a buyer gino till I supposed to do so into future windows Doggett, we'd be selected and Stephen It's fair to say, though the.

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

Or top an image and the central indications for tow those old belong to by region.

Anvita Gupta: Yes, there is no carve-out. All indications targeting tau, for example, PSP or Alzheimer's, will belong to Biogen.

Yes, there is no there's no came about oney indication.

Targeting Oh, you know tower for example, PSB zima, we'd be looking to buy a gene.

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

Got it and can you talk to I guess that process before selection of the additional nine targets I guess there were certainly.

Level of.

Preclinical data or in vitro day that you guys will generate.

And then a decision making time period.

That.

Ah that Viking has or is it whatever they want to pick up whatever time within that.

Stefan: Stanley, do you want me to answer? Yeah, so we cannot disclose a lot of details, but of course, we need to bring to Biogen a certain preclinical package or a certain validation package. And the deal is structured in a way that we are at Sangamo strongly incentivized to bring those packages as rapidly as possible to Biogen.

Five years.

Andy you want me to answer yes, so we cannot.

Disclose a lot of details but of course, we are we need to bring to Biogen a sell 10 picking equal package also and validation package.

The duly suite utility in a way that we had some capital is totally incentivized to bring those package as rapidly as supposed people too soon to Biogen.

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

Got it.

My next question was actually on some.

Either learning or more my question is what not to do in a competitor Fabry gene therapy program presented at World.

Clinical phase one 280 program at showed I believe it was my heart I just think well then elevation in Fabry I was wondering if you guys saw that presentation thought fine.

Yes that is a risk to any avi in fabry, that's something that with.

That's fair specific in and just sort of lessons from that program and go sit here as you think about Europe.

Alexander D. Macrae: Yes, we saw that data, and... One 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 AV6 we've got a lot of experience now across Haemophilia A and the IVPRP programs, and this is something we have not seen in the clinic, and we have not seen in any of our pre-clinical models, so we are, We are pleased that we haven't seen this issue, but we'll always remain vigilant and hope that Freeline finds a way forward.

Yes, yes, we felt we saw that Dayton and.

One when there's always careful to comment on safety issues that are our friends and other companies. How could you don't know all the details and patient safety and lives are important what I can see though is with our 86, we've got a lot of experience no across hemophilia, a and the IB PRP.

Programs and this is something we have not seen in clinic and we have not seen any ofer preclinical models. So we are.

We are pleased to we haven't seen this this issue, but will always remain vigilant.

And I hope the feline find a way forward.

Anvita Gupta: Is there a rationale, like a medical rationale, for why FABRI patients could see a unique toxicity because of FABRI cardiomyopathy?

Is there a rationale we got a medical rationale for why they see.

Fabry patients can see a unique toxicity because of Sabri cardio my obviously.

Alexander D. Macrae: So the Fabry patient, as I think I know where you're going with the question, the Fabry patients do 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, as everyone else will, to make sure that our patients are protected and that we start at the right dose and that we look after these patients with all due caution.

So that their fabry patients as I think kind of where you're going with the question. The fabry patients do have cardiac disease and it may be that there is a susceptibility there which is why as I was pleased we are with our safety profile up to know we will.

Watch with that as everyone else will to make sure that our patients are protected.

And we start to the right those until we really look after these patients with the was old you caution.

Anvita Gupta: Has that fed in at all to your careful screening, and can you talk about why you have such high screen failures so far?

Has that setting it all to your the your careful screening and can you talk to why you have such high screen failures.

Alexander D. Macrae: So, I would refer you to Bettina's answer. We would refer you to Bettina's answer. The screening problem, sorry, the screen challenge is not around the AAV neutralized antibody. That remains about 30%.

So far.

So I I would refer you to between us on Sir.

You know.

Just.

We refer you to between us on so to.

The screening problem sorry, the screen challenge is not to read into E. V. Neutralizing antibody that remains about 30%, it's about understanding the disease and being very careful in choosing the right patients.

Alexander D. Macrae: 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 is available in their notes and how we can find them and bring them into the study. We look forward to bringing patients in very soon.

And I think were old learning a bit factories to season, which are the right patience import data and is available in their notes and how do we can find them and bring them into the study.

We look forward to bring patients and very soon.

Anvita Gupta: Great, thanks for taking the questions.

Great. Thanks for taking my question.

Umair Rafat: Thank you, and our next question comes from Umair Rafat with Evercore ISI. Your line is open.

Thank you and our next question comes from America, Refaat with Evercore ISI. Your line is open.

Mike DiCiore: Hi, this is Mike DiCiore in for Ulmer. Thanks so much for taking my question and huge congratulations on the deal.

Hi, This is my tissue already in for a little more thanks, so much for taking my question and huge congrats on the deal I've. A question that that's partially related to previous question that was asked.

Mike DiCiore: I have a question that's partially related to a previous question that was asked. You know, given that Biogen is already developing ASL pipeline assets specifically in Alzheimer's and Parkinson's... You know, you said not too long ago that this ASO approach may be suboptimal, in that it wouldn't be a complete silencing or... turning off of genes. So my question is, will Sangamo's zinc finger nucleus approach be complementary? Or can these two approaches be used together in treating these diseases?

You know given that that biogens already developing asked so pipeline assets that specifically in Alzheimer's and Parkinson's.

You know he said in that's a long ago that.

Yeah. So approach may be suboptimal in that it wouldn't be a complete silencing <unk>.

Turning off of genes. So my question is well well, saying about zinc finger nuclease approach could it be complimentary or where can these two approaches be used together in treating these diseases. Thank you.

Alexander D. Macrae: Thank you.

Adrian: An interesting question, Adrian.

[noise] interesting question Adrian.

Yeah, I think I think this will most certainly will be a role for both approaches and I think it remains to be seen how they play together and I'm sure Biogen has very specific ideas about that and probably best to to leave it to that development seem to see you know just began to that in more detail.

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

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

But to be clear, we hope that our product to see answer and its unnecessary to dose with anything else.

Alexander D. Macrae: Thank you.

Thank you.

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

Thank you and our next question comes from Philly, So, yes with Mizuho. Your line is open.

Bennett: Hi, good morning. This is Bennett from Salim's team at Mizuho.

Hi, Good morning, I did just Bennett from selling theme I mean, so first of all congrats on your thoughts on on the deal and thanks for taking the questions. So just a couple of quick ones for us.

Bennett: First of all, congratulations 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, ST501 and 502, did you find any off-target genes downregulated? And second, in the context of Parkinson's disease, if I'm not wrong, since alpha-synuclein has several transcription starting sites, are you targeting certain TSSes or others? Thank you.

And your studies for these two candidates as Steve I for one and I thought too if you find any target genes sounds like related.

And second in the context of Parkinson disease, if I'm wrong thing Alpha Synuclein Hospital Cascade kind of how to think side are you targeting halftime DSS other other thank you.

Adrian: These are very good questions.

These are very good questions Adrian.

Adrian: Yeah, I didn't hear the second question, but let me... The second question was about the various start sites that are... Oh, I see, right....a present person in Ukraine.

I didn't hear the second question, but let me second was supposed to start the theory start sites or Oh, I see RASM person Ukraine, yeah. Yeah. So so let me just talk about the first one so why is the really important differentiating features about all technology say for example to Chris but is that zinc fingers proteins.

Adrian: Yeah, yeah. So one of the really important differentiating features about our technology, say, for example, to CRISPR, is that zinc finger 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 may have seen, we published a really, really wonderful paper.

All proteins right and that means that the engineer ripple in a way that's just not possible to two to do with Chris but.

And some of you would've seen we published a really.

Well actually wonderful pay per my my colleague agree balls team.

Adrian: My colleague Ed Rebar's team wrote the paper, and they showed how they could reduce off-target for nucleases, which of course, we're not using in this situation. But in the case of nucleases, by tuning the catalytic rate of FOC1, but in the case of transcription factors, we had another way of reducing off-target, and it was through the mutation of arginine residues, which make nonspecific contacts And by mutating out those residues to glutamines, we could reduce off-target effects to virtually zero. And the data's actually really striking when you see it.

Right. The paper and then they showed how they could reduce off target.

For new cases, which of course, we're not using this situation, but in the case of new cases by you know cheating there.

The catalytic rights of four columns in the case if transcription factors. We we had another wave of reducing of talk again. It was through the mutation of all Jeanine residues, I'm, which make nonspecific contacts with the negative charged with the DNA Phoenix and by me taking out.

It was arrested used to Greece means we could.

Reduce of target to virtually zero in the dates is actually really striking when you said I mean this is a phenomenal invention bio team because without these mutations do you get you know you significantly more off target. So Oh reagents now contains mutations so we believe we more or less.

Adrian: I mean, this is a phenomenal invention by our team, because without these mutations, you get significantly more off-target. So our reagents now contain these mutations, and we believe we more or less completely eliminate off-target, and that probably makes them the safest reagents of this kind. And of course, just on another related safety point, these are human, fully human proteins. Remember that because both the repressor component and the zinc finger itself are derived from a natural, recapitulating, natural human gene regulation in the brain, so that's very different. And Adrian, we would refer them to the patient on the paper about tau, where we show that it's only the tau gene that is repressed.

Completely eliminate self cog and that probably makes him the safest reagents at this kind of course, just on another related safety point Nisa human fully human proteins, right remember that because both the rhopressa component and the zinc finger itself.

As to Rifleman and you know not true Recompete tracing natural human gene regulation in the brains that that's very different management, we would refer them to the patient on the paper on toe, where we show that is only the total gene touches repressed. So yeah. So from an off target point of view from from Tony We have already public.

Adrian: Yeah.

Adrian: So from an off-target point of view, for Tau, we have already published that data. And for Sinuclein, the asset that we would take forward, we would plan to have it with a similar sensitivity.

We start data and for some new thing the I said that we would take forward. We would plan to have it with is similar sends out of it and the activation or pressure and because we can be biased but in this case repression is intrinsically localized orange related to the target gene by the cells nicest machinery that.

Alexander D. Macrae: And the activation or repression, because we can do both, but in this case, repression is intrinsically localized or insulated to the target gene by the cell's native machinery that prevents the effect from spreading to adjacent genes.

That prevents the effects spreading into adjacent games.

Alexander D. Macrae: And then your question on sunuclein is an interesting and very technical one, and we haven't revealed which of the start sites that we are targeting, but Again, it's within the ability of this technology to choose across the start sites and tile across that, which one we're going to do. So we will talk more about that in weeks and months to come.

And then your your question on some new clean as an interesting and very technical one and we haven't reviewed which at the start sites that we are targeting but again, it's within the the ability of this technology to choose a cross the start sites and tie all across the switch.

One we're going to do so we will we will talk more if that in and weeks and months to come.

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

Thank you. Thank you what I meant that was helpful.

Alexander D. Macrae: 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.

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

Alexander D. 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 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.

Thank you for joining us today and for your questions. This really is an exciting day for saying one and for patients with with devastating neurological diseases with our technology and Biogens understanding of the signs on the medicine and on the patients already there, we really who we can do something special so we appreciate your 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.

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

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Operator: Thank you for watching!