Q2 2021 Sangamo Therapeutics Inc Earnings Call
Of the Sangamo second quarter of 2021 teleconference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session. The ask.
Operator: call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press the star one on your telephone. Please be advised that today's conference is being recorded. And if you require any further assistance, please press star zero.
The question during the session.
You will need the press the star 1 on the telephone please be advised that today's conference is being recorded and if you require any further assistance. Please press the star Zero I would now like the hand, the Congress over the of speaker of today, the head of the corporate Communications Ms. Erin Feingold Pease go ahead.
Operator: I would now like to hand the conference over to your speaker today, the head of corporate communications, Ms. Aaron Feingold. Please go ahead.
Aaron Feingold: Good afternoon, and thank you for joining us today. With me on this call are several members of the Sangamo Executive Leadership, including Sandy McRae, Chief Executive Officer, Mark McClung, Chief Business Officer, Pratusha Derey Badu, Chief Financial Officer, and Jason Fontno, Chief Scientific Officer. Rob Schott, Head of Development, and Bettina Cockroft, Chief Medical Officer. Slides from our corporate presentation can be found on our website, Sangamo.com, under the Investors and Media section on the events and presentations page.
Good afternoon, and thank you for joining us today.
With me. This afternoon on this call are several members of the Sangamo executive leadership team, including Sandy Macrae, Chief Executive Officer, Mark Mcclung, Chief business Officer for 2 surgery of Baidu, Chief Financial Officer, Jason Park, now Chief Scientific Officer, Rob shot.
Head of development, and Bettina Cockroft, Chief Medical Officer price.
Slides from our corporate presentation can be found on our website sangamo dot com under the investors and media section on the events and presentations page.
Aaron Feingold: This call includes forward-looking statements regarding Sangamow's current expectations. These statements include, but are not limited to, statements relating to potential value drivers, clinical catalysts, and advancement of our pre-clinical type line, plans and timelines for enrolling and conducting clinical trials and presenting clinical data, potential clinical data out our 2021 financial guidance, our expectations regarding our financial performance and sufficiency of our cash resources, and other statements that are not historical. actual results may differ materially from what we discussed today.
This call includes forward looking statements regarding single most current expectations. These statements include but are not limited to statements relating to potential value drivers clinical catalysts and the advancement of our preclinical pipeline plans and timelines for enrolling in conducting clinical trials.
Presenting clinical data potential clinical data outcomes, our 2021 financial guidance, our expectations regarding our financial performance and sufficiency of our cash resources and other statements that are not historical facts.
The well results may differ materially from what we discuss today.
Aaron Feingold: These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC, specifically our annual report on Form 10K for the fiscal year ended December 31, 2020, as supplemented by our quarterly report on Form 10Q for the fiscal quarter ended June 30, 2020. The forward-looking statements stated today are made as of the date of this statement, and we undertake no duty to update such information except as required by law. On this call, we discuss our non-gap operating expenses. Reconciliation of this measure to our gap operating expenses can be found in today's press release, which is available on our website. Now, I'd like to turn the call over to our CEO, Sandy McLeod. Thank you, Aaron.
These statements are subject to certain risks and uncertainties that are discussed in our filings with the S. E. C. Specifically our annual report on form 10-K for the fiscal year ended December 31, 2020, as supplemented by our quarterly report on form 10-Q for the fiscal quarter yet.
Ended June 32021, the forward looking statements stated today are made as of the state and we undertake no duty to update such information, except as required by law.
On the call we discussed our non-GAAP operating expenses reconciliation of this measure to our GAAP operating expenses can be found in today's press release, which is available on our website.
Now I'd like to turn the call over to our CEO Sandy Macrae.
Thank you.
Good afternoon to everyone on the call.
This is an exciting time at signs of them as we look forward to multiple clinical catalysts over the next several quarters representing potential near term volume drivers.
Alexander D. Macrae: And good afternoon to everyone on the call. This is an exciting time for the company, as we look forward to multiple clinical catalysts over the next several quarters, representing potential near-term value drivers. At the same time, we're advancing our promising preclinical pipeline that focuses on our differentiated CARTREG approach for autoimmune diseases and genome engineering for CNS diseases towards INDs, which represent potential mid-term value drivers.
At the same time, we are advancing our promising preclinical pipeline. The focus is on our differentiated car T. Reg approach for autoimmune diseases genome engineering for CNS diseases towards R&D.
Congrats on your potential return some of your drivers.
Beyond the we continue to invest in early stage research to further mindful of you from a core zinc finger platform.
We continue to make steady progress on other wholly owned fabry disease phase 1.2 clinical studies.
During the quarter, we dosed the first patient on based on the initial safety data from patients dosed to date, the safety monitoring committee endorsed dose escalating to the third dose of clients from the sort of the protocol.
We're currently screening patients for the third dose cohort unexpected to us the first 2 patients in this third cohort by the end of the year.
Alexander D. Macrae: Beyond that, we continue to invest in early stage research to further increase mine value from our core zinc finger platform. We continue to make steady progress on our wholly owned Fabry Disease Phase 1-2 clinical study. During the quarter, we dosed a fourth patient, and based on initial safety data for patients' dose to date, the Safety Monitoring Committee endorsed dose escalation to the third dose as planned under the Surrey Protocol. We're currently screening patients for the third dose cohort and expected to dose the first two patients in this third cohort by the end of the year. We will make a decision on when to first present initial data from this study, depending on clinical timelines, and we'll publicly announce our plans when available.
We will make a decision on the went to the first present initial data from the study depending on clinical timelines on those.
Couple of clean them sort of plans when available.
Yeah.
In addition, we currently have 3 sites open in what we believe is the first in human car T. Rex study.
And we plan to enroll the first patient for the end of this year.
We're very excited about the study.
We believe this proof of concepts of evaluating TX 200, kidney transplant rejection will help us understand car T Reg pharmacology and biology in humans as well as the advanced process to build the knowledge.
We hope the study establishes the foundation for the portfolio of wholly owned car T Reg therapies for autoimmune indications.
In the fourth quarter of this year, we and Pfizer expect to present 2 year results from the phase 1.2 ultra study in hemophilia a.
We look forward to having a clearer understanding of the durability through 2 years from the 5 patients from the high dose cohort from the phase 1.2 ultra study as well as from the phase III data from additional patients and we expect to reach out to 2022.
Together these data will be highly informative about the potential product profile.
Alexander D. Macrae: In addition, we currently have three sites open and what we believe is the first inhuman CAR2 rec study, and we plan to enroll the first patient at the end of this year. We're very excited about this study. We believe this proof of concept study evaluating TX-200 in kidney transplant rejection will help us understand CART-RIG, pharmacology, and biology in humans, as well as advanced process development knowledge. We hope this study establishes a foundation for a portfolio of wholly owned Carty Reg therapies for autoimmune indications.
In addition, leaps of this year, we on our partners. Some of you expect to share of initial phase 2 data from our precision 1 study of its an upcoming medical meeting.
The study is investigating SCR for for 5 <unk> 6 for the treatment of sickle cell disease.
We expect to report interim efficacy and safety data for the first for patients dosed with at least 3 months of follow up.
Finally, Biogen recently selected the for neurological disease gene target under the collaboration agreement.
And we have begun early research activities on therapies addressing this target.
This quarter, our former general counsel, Gary made the personal decision to leave cycle from the other opportunity, we thank him and wish him well in his future.
However, we are pleased to data of notes that we of promoter score will it be too general counsel on corporate Secretary.
Scott has contributed significantly to signs of overseeing all corporate law on compliance metrics since he joined US in March 2020.
Scott has over 20 years of legal experience with expertise in corporate government's FCC reporting corporate finance compliance mergers and acquisitions on transactions.
Alexander D. Macrae: In the fourth quarter of this year, we at Pfizer expect to present two-year results from the Phase 1-2 Ulta study in hemophilate A. We look forward to having a clearer understanding of durability through two years from the five patients in the high-dose cohort from the Phase 1-2 Ulta Study, as well as from the Phase 3 data from additional patients that we expect to read out in 2022. Together, these data will be highly informative about the potential product profile.
In addition to Scott's appointment of our executive team with recent strength by the appointment as our new Chief Financial Officer, Patricia debt or a bumper. Patricia has served a sangamo principal accounting officer for nearly 2 years.
She has contributed significant with a wealth of experience on her proven track record and optimizing financial strategy and operations driving operating organizational change on building diverse teams.
So pleasing to promote from within talented individuals.
I look forward to Scott and Patricia is leadership.
And with that I'll turn the call over to Patricia for a financial update.
Thank you Sandy and good afternoon. It has been my pleasure to serve of Sangamo Chief Financial Officer for the POS came on.
Alexander D. Macrae: In addition, later this year, we and our partner, Sanofi, expect to share initial phase 12 data from our precision one study, investigating SAR 445136 for the treatment of sickle cell disease, at an upcoming medical meeting. We expect to report interim efficacy and safety data for the first four patients dosed with at least three months of follow-up. Finally, Biogen recently selected a fourth neurological disease gene target under a collaboration agreement, and we have begun early research activities on therapies addressing this target.
I look forward to continued interactions with all of you as we progress of business forward.
On until the first for the quarter are available in the press release issued this afternoon, which can be found on our website.
This quarter, we continue to invest on the advancement of our clinical programs of preclinical research pipeline and expanding our in house manufacturing capabilities.
We ended the quarter with approximately $579 million in cash cash equivalents and marketable securities.
We believe that our balance sheet remains strong and will allow us to reach several important R&D milestones, including the potential submission of the BLA for our hemophilia a part of attendance.
Turning to 2021 full year guidance, we would like to reiterate the guidance we provided in the prior calls.
We continue to expect non-GAAP operating expenses, which excludes estimated noncash stock based compensation expense of approximately $30 million for being in the range of for $55 million of the $175 million for the year.
We will now turn it over to the operator to open the line for questions operator.
Thank you.
So all of our phone participants if you wish to ask a question. Please press the star 1 on your telephone again. Please press the star 1 on your telephone that's possible a few seconds as we compile the Q&A roster.
And our first question is from Maury Raycroft of Jefferies. Please go ahead.
Okay.
Hi, This is Kevin on the line for.
Today, Thank you for taking my questions.
So for TX 200.
There are some prior disclosures I think from TX <unk>, which discussed use of <unk>.
Prathyusha Duraibabu: This quarter, our former General Counsel, Gary Lowe, made the personal decision to leave Sangle for another opportunity. We thank him and wish him well in his future. However, we are pleased today to announce that we have promoted Scott Willoughby to General Counsel and Corporate Secretary. Scott has contributed significantly to Sangam, overseeing all corporate law and compliance matters since he joined us in March 2020. Scott has over 20 years of legal experience with expertise in corporate governance, SEC reporting, corporate finance, compliance, mergers and acquisitions, and transactions.
Fox P 3 and use of anti virus.
And there are a number of car T. Reg competitors moving forward in the space on the technical side, what should investors be focused on when trying to appreciate differentiation of Sangamo is approach with TX 200 versus what competitors are doing.
So this thank.
Thank you for your question I think this is 1 that we're the best answered by Jason <unk>, Our Chief Scientific Officer, Jason.
Yes, Thank you family.
Hi.
So the sangamo.
For the partnership.
Of that Sangamo.
Started with <unk> with the acquisition of the legacy Tfl group brought together our extraordinary genomic engineering platform with the expertise that <unk> built and key red biology over the years.
That work has only grown and matured over the last years as we've continued to push forward, our TX 200 program as well as the programs that we're advancing behind that.
For multiple sclerosis, and inflammatory bowel disease.
Turning to that we are very invested in moving from autologous cell therapies to allogeneic cell therapies through the use of our.
Zinc finger of genomic engineering platform.
Prathyusha Duraibabu: In addition to Scott's appointment, our executive team was recently strengthened by the appointment of our new chief financial officer, Patricia Darry Bambo. Patricia has served as Fangom's principal accounting officer for nearly two years. She has contributed significantly with her wealth of experience and her proven track record in optimizing financial strategy and operations, driving organizational change, and building diverse teams. It is so pleasing to promote from within talented individuals, and I look forward to Scott and Patricia's leadership. And with that, I'll turn the call over to Patricia for a financial update.
Through our partnership with Micrify, none of our internal work on Ips CS.
So the real differentiator for me between what Sangamo is doing and what the new entrants into the field or is it.
Simply the the breadth of expertise that we have on the time that we've invested here.
And we're super excited about the programs.
The potential to really transform the treatment of autoimmune disease.
Great Thanks and the.
Then just on the AAV side, so when considering discussion on AAV safety and evading the immune system.
<unk> has been an innovator there are there any new developments on the AAV side that you can talk about particularly with <unk> that can be used with your neuro programs.
So.
Thank you for that question too we continue to.
Invest in.
Our group within Jason's organization, the or looking at optimizing AAP use with the CNS spoke about this this year is GCT.
<unk> will talk about the as the data of bowls, we have some very smart scientists doing this on.
Prathyusha Duraibabu: Thank you, Sandy, and good afternoon. It has been my pleasure to serve as Sangamo's chief financial officer for the past few months, and I look forward to continued interactions with all of you as we move our business forward. Our financial results for this quarter will be available in the press release issued this afternoon, which can be found on our website. This quarter, we continue to invest in the advancement of our clinical programs, our preclinical research pipeline, and expanding our in-house manufacturing capabilities.
And we.
We are of the opinion the delivery is so important for genomic engineering. It goes hand in hand, with the molecular biology of the zinc fingers and we look forward to sharing more data in the months to come.
Great. Thanks for taking my questions.
And our next question is from the A&M Xu of Wells Fargo Securities. Please go ahead.
Hi, Thanks for taking my questions.
A question on the Fabry disease program, I guess I'm wondering Inc.
For you to determine of dose to move into the dose expansion what data point.
The data points would you pay attention to and what kind of a follow up would you require in order to make that call.
And also you know each day as the dose level has only 2 patients do you feel that you have enough data points to to make the determination of the the dose for the expansion and lastly, how many patients do you think you would enroll into the dose expansion study. Thank you.
Prathyusha Duraibabu: We ended the quarter with approximately $579 million in cash, cash equivalence, and marketable security. We believe that our balance sheet remains strong and will allow us to reach several important R&D milestones, including the potential submission of a BLA for our Hemophilia A product candidate. Turning to 2021 full-year guidance, we would like to reiterate the guidance we provided in our prior call. We continue to expect non-gap operating expenses, which exclude estimated non-cash stock-based compensation expense of approximately $30 million, to be in the range of $255 million to $275 million for the year. We will now turn it over to the operator to open the line for questions. Operator? Thank you, to all our phone users,
Thank you and portion of questions of boat study for us.
We're very passionate but so can I turn this to Mark and then get rolled 2 to add to and from the clinical point of the let's start with Mark.
Okay.
Yes.
Thanks for your question.
A lot of these questions are related to the trial I mean as you probably are aware of the star studies primary endpoint of safety and Tolerability.
On the secondary endpoints of our pharmacodynamics of Alpha Gal, a and the presence of the substrates in the plasma over time.
As well as the impact on eventually on the <unk> administration.
What I'll do is maybe hand, it over to Rob to answer the specific questions in terms of where we're at with the dosing cohorts and.
And how will we will progress into the expansion cohort.
Yeah. Thank you very good question.
We have announced that the Dms.
The data safety monitoring board has met.
<unk> has endorsed.
R R.
Operator: To all our phone participants, if you wish to ask a question, please press 1 on your telephone. Again, please press 1 on your telephone.
Moving to the third dose cohort. So we have fulfilled the safety requirements and additional requirements for the independent the MSP to allow us to proceed to our highest dose cohort.
We're not disclosing at this point of the specifics of that but we are.
Moving to the cohort then and plan to dose. The next 2 patients in the cohort this year and we'll be sharing data.
Operator: Let's pause for a few seconds as we compile the Q&A roster. And our first question is from Morriekroff of Jeffries. Hi, this is Kevin on the line for Mori today.
On the.
Clinical timeline.
The appropriate.
But.
Again, the most of it.
Kevin Harrington Strang: Thank you for taking my questions. So for TX200, there were some prior disclosures, I think, from TXL, which discussed the use of Foxp3 and the use of one T-virus. And there are a number of CART-Reg competitors moving forward in the space. On the technical side, what should investors be focused on when trying to appreciate the differentiation of Sangamu's approach with TX200 versus what competitors are doing?
Horton piece of information.
Of that we're sharing with respect to your question is that the the MSP.
Hmm.
Approved unanimously the share.
The court.
Yeah.
Yeah.
Okay got it got it thanks for the color.
And our next question is from Geoff Meacham Bank of America. Please go ahead.
Hey, guys, it's Aspen on for Jeff Thanks for the questions.
So I'm just kind of follow up on the last question can you remind us on the on the dose levels of 3 dose levels for fabry.
I know obviously on some other gene therapy trials from the past, yes, the the lower doses weren't quite as adequate on higher dose of kind of address the level of efficacy from other companies looking for different programs I guess I'm just kind of get a sense of is is that what we're seeing there.
Or was this dose escalation of always kind of part of the plan.
And based on the dose escalation of is the primary driver the.
Alpha Gal a levels that youre looking at the C.
Yes. Thank you.
So let me let me say this on a new this is this must be so frustrating for all of you we have not revealed the 2.
So if it was for going in other.
Alexander D. Macrae: So this, thank you for your question. I think this is one that would be best answered by Jason, our chief scientific officer. Jason. Yeah, thank you, Sandy.
The next 3 cohorts.
We have learned a great deal from the hemophilia a study of both the kind of levels that are appropriate.
And it's always.
Patient.
Jason D. Fontenot: So Sangamo, the partnership that Sangamo, started with TXL, with the acquisition of the Legacy TXL group, brought together our extraordinary genomic engineering platform, with the expertise that TXL had built in TRED And that work has only grown and matured over the last years as we've continued to push forward, PX 200 programs, as well as programs that we are advanced, for multiple school roads, addition to that, we are very in moving from cell therapies to allergenic cell therapies through the use of our zinc finger genomic engineering platform, and through our partnership with Mogrify and our internal work on So the real differentiator for me between what Sangamo is, is simply the breadth of expertise that we have and the time that we've invested here, excited about the program, and the potential to really, Great, thanks. And then just on the AV side, so when considering discussion on AAV safety and evading the immune system, Sango has been an innovator there. Are there any new developments on the AV side that you can talk about, particularly with AVs that can be used with your neuroprograms?
Agency of boat starting of doors, the gifts of patients from hope of benefit for us.
As being prudent for something that is the first time, except for going on to human.
And.
We are immensely grateful for patients coming in taking that for stores.
Knowing until we see the results for Theres been any benefit to them. So we're going to the 3 doses and we hope to be able to describe the dose effect across the 3 doses.
Okay. Thanks, and maybe just 1 quick follow up.
So the the Fda's listing of Dotcom I think in early September.
Maybe just help us frame, what your expectations for that or if youll be at all involved from that meeting.
With 1 of your opinion on them.
We have the group.
For stuff that will be attending virtually or in person meeting.
Each company has dose of <unk> patients with ADP. The the agency has the greatest store of the knowledge on the safety and efficacy of <unk>.
And so I.
On looking forward to the meeting and looking forward to hearing.
The things that the agency fees across many programs. So as we can all learn and the patients can be protected.
Much of as possible.
Okay, great. Thanks Sandy.
Yeah.
And our next question is from Gena Wang of Barclays. Please go ahead.
Thank you my first question lots of follow up on the <unk> family.
The program that I just wanted to ask.
The exactly what kind of the level, if you can give a little bit more quantitative.
So regarding the work by looking for to define as the right.
For example, the line from GPC I'll be talking about over 50%.
The reduction of or.
Even below <unk> level.
So this is the first question second question of the Hemophilia a program.
Just wondering if true you affect the level at some decline do you expect FTE will ask for longer than for 1 year follow up for.
Alexander D. Macrae: So thank you for that question too. We continue to invest in a group within Jason's organization that is looking at optimizing AAP use within the CMS. We spoke about this this year at ASGCT, and we'll talk about it as the data evolves. We have some very smart scientists doing this. And we are of the opinion that delivery is so important for genomic engineering. It goes hand in hand with the molecular biology of the zinc fingers.
The phase III study.
Okay.
Good afternoon, Jami, So let me answer those questions in reverse order of the.
The Pfizer is handling the communication and the regulatory interactions around chief of affiliates and volume.
I'm. So pleased that the BP is being looked after price or the new the due to a great job in helping boost regulatory conversations.
Operating model.
A discussion of what we're looking for for to determine success.
Yeah.
Yes.
Sorry apologies.
The the program goal is to look for a predictable durable expression of the Alpha Gal a enzyme and then.
To see whether or not that results in the accumulation of the substrates of GBP 3 and the soluble derivative license of GBP..3 go down we've not commented on the amounts that we have.
Operator: And we look forward to sharing more data in the months to come. Great, thanks for taking my questions. And our next question is from Yain and Zoo from Wells Fargo Securities. Please go ahead.
We're expecting to see.
As for.
Randy mentioned.
Most of the first for patients.
We're moving into screening for the the third dose cohort, which is terrific and hopefully we'll have an update for you by the end of the year in terms of when you might start seeing some of that data.
I'm sorry, the price and just wondering I understand you cannot talk about the for.
Yanan Zhu: Hi, thanks for taking my questions. So a question on the Fabry's disease program: for you to determine a dose to move into the dose expansion, what data points would you pay attention to and what kind of follow-up would you require in order to make that call? And also, you know, each dose level has to be a question. With only two patients, do you feel that you have enough data points to make a determination of the dose for the expansion? And lastly, how many patients do you think you would enroll in the dose expansion? Thank you.
2 cohort data, but just wondering what is your goal to the timing okay. That's the right dose.
We have not commented on that Jamie.
I know some of the other companies have commented on the percent substrate reduction of a bio has done that but we are.
Our belief is obviously you'd want to see.
Fairly significant reduction in the substrate because that seems to.
Linked to the improvement for the in the decline of the Egfr, which is really important for patients.
That's true.
Thanks.
But the June.
I'd want to strike a note of caution issue interpret the upper biotech accounts.
The reduction in G. P..3 will depend on the license.
The license you can see we spend on where you start to.
So if you have the high level of license of GPS III on your company. This effective you'll get the reduction if your license GPS III is already at the low level <unk>.
Sure.
It's.
2.2 of reduction the.
Alexander D. Macrae: Important questions about a study that we're very passionate about. So can I turn this to Mark and then get wrong to add in from a clinical point of view? But let's start with Mark.
Dramatic.
Graph that.
Shows is on.
Artifact of the patient that they recruited.
Okay. Thank you.
And our next question is.
He is from Ritu <unk> of Cowen. Please go ahead.
Yeah.
Hey, guys.
I wanted to just follow up on Fabry again.
Mark McClung: Yeah, thanks for your question. You know, a lot of these questions are related to the trial. I mean, as you probably know, the primary endpoint of STAR studies is safety and tolerability. The secondary endpoints are pharmacodynamics of alpha-gal-A and the presence of the substrates and the plasma over time, as well as the impact on eventually on ERT administration.
Can you I know you can't really tell us about the safety findings, but I'm kind.
I'll ask Inc.
What has been observed and learned on the cohorts to date on the.
The preclinical I guess investigation to bolt on.
What does it how you about on the safety of the program.
Not just the standard.
The liver or complement of issues, but also.
Rob Schott: What I'll do is maybe hand it over to Rod to answer the specific questions in terms of where we are with the dosing cohorts and how we will progress into the expansion cohort. Yes, thank you. Very good question.
The cardiac safety with in the Fabry population, just given the competitive programs of Shen signals.
Is this something worth waiting patients out for or.
Or is this something that could be unique to various programs.
And then I have a hell of a lot.
So let me answer the slightly tangentially, it's remarkable because we have dosed with AEP 6 of across a number of programs and also on the occasional and immune response of luxury response or vacation L. T.
Rob Schott: We have announced that the DMSB, the data safety and monitoring board, has met and has endorsed our moving to the third dose cohort. Thus, we have fulfilled the safety requirements and additional requirements for the independent DMSD to allow us to proceed to our highest dose cohort. We're not disposing at this point to the specifics of that, but we are moving to that cohort and plan to dose the next few patients in the cohort this year.
Considering how much far sort of giving is remarkably safe. These viruses are are the <unk>.
2 of them as very encouraging.
The second thing is that we do not determine the safety of ourself to have the DSM be the.
Overviews all of the safety and allows us to carry on.
Rob Schott: And we'll be sharing data along the clinical timeline as appropriate. But again, the most important piece of information that we're sharing with respect to your question is that the MSB unanimously approved the third dose card. Okay, got it, got it, thanks for the color. And our next question is from Jeff Mecham, Bank of America. Hey guys, it's Asron for Jeff.
You mentioned the treeline.
How does the DSM b or some safety monitoring committee the.
Then the pud of judge their cardiac events and given the council on put the or not they could.
The funds we have heard.
Very clear unanimous response from the TSMC.
Got it.
That is very helpful.
And then just because manufacturing build out.
Is.
The prominently featured on the update of how should we be thinking about capex.
Aaron: Thanks for the questions. I'll just kind of follow up on the last question. Can you remind us of the dose levels, with three dose levels for Fabri? I know, obviously, in some other gene therapy trials in the past, the lower doses weren't quite as adequate, and higher doses kind of addressed the level of efficacy. Some other companies looking for different programs. I guess I'm just trying to get a sense of, is that what we're seeing here? Or was this dose escalation always kind of part of the plan?
Capex allocation for the manufacturing build out across the lead programs.
Patricia.
Gives us on the.
Our manifesting, though that is going to the based on what they need of close of different programs.
We will assess it and the next day.
Here of 6 months to 18 months.
Yeah.
Got it.
Oh go ahead.
I'm, so glad we invested in manufacturing.
18 months 2 years ago and.
They are on the Earth.
Completed as of the manufacturing their own track to do so the repeats manufacturing in Brisbane and the bonds by the end of the year.
Alexander D. Macrae: And, and, you know, if social escalation is the primary driver, the alpha-gal levels that you're looking at to see? Yeah, thank you. So let me say this, and I know this must be so frustrating for all of you.
And the reason I say that is the.
There is.
The.
Between the idea and clinical material and manufacturing as well for a year no matter who does it.
And.
The debt.
As of Q no the.
Cmo's for manufacturing slots.
Alexander D. Macrae: We have not revealed the levels we're going in other than there are three cohorts. We have learned a great deal from the hemophilia study about the kind of levels that are appropriate, and it's always a patient, agency decision about starting at a dose that gives the patient some hope of benefit versus being prudent for something that is the first time it's ever gone into humans, and we are immensely grateful for patients coming and taking that first dose, not knowing until we see the results whether there's been any benefit to them.
But more importantly, if you look of what's happened with other EV companies. It's the quality of manufacturing is the most important regulatory.
Discussion on I filled by having our research group side by side with our manufacturing group to do process development, we have the best chance of the best product on the process as the product.
So I think it was of a wise investment we've made.
Yeah.
Got it and then on Sandy I just want to triangulate your comment in the slides that were sent around.
Alexander D. Macrae: So we're going to have three doses, and we hope to be able to describe the dose effect across the three doses. Okay, thanks, and maybe just one quick follow-up. So the FTA is hosting a meeting in Adcom, I think, in early September on AAV. Maybe just help us frame what your expectations for that are, if you'll be at all involved in that meeting. I would love to get your opinion on that. We have a group of our staff that will be attending that meeting either virtually or in person.
Especially in relation to the Biogen collaboration.
You had mentioned the progress on the Biogen program with the undisclosed target I want to make sure. It's that like on Slide 22, you have alpha for new claims how all of the thief and on.
Undisclosed you're referring specifically to the undisclosed neurology target or should we be thinking about progress on 1 of the debt free.
Jason can you help disentangle the many targets are on the corner and Biogen.
We now have.
Yeah.
Sorry about that we now have for targets.
Hum in the in the Biogen.
Alexander D. Macrae: Each company has dosed so few patients with AAV that the agency has the greatest store of knowledge on the safety and efficacy of AEV. And so I am looking forward to the meeting and looking forward to hearing the things that the agency sees across many programs. So that we can all learn and that patients can be protected as much as possible. Okay, great. Thanks, Andy. And our next question is from Gina Wang of Barclays.
The collaboration.
The thrilled.
No.
See them progressing.
Great to be working with the partner like Biogen.
That the.
The fact that we are progressing on on all of these targets is a reflection of.
Just how much confidence the Biogen team has in the work.
Debt.
The Sangamo team is doing.
To support these programs so.
I'm really looking forward to.
When Biogen can can tell everyone more about the targets.
And about the work that we're doing.
When it's appropriate we will certainly be able to to publish the work that we've been doing to support the team.
And Jason before you go back on back on mute, we had we recently had the.
Alexander D. Macrae: Please go ahead. Thank you. My first question also follows up on the February disease program, and I just wanted to ask, you know, exactly what kind of level if you could give a little bit more quantitative answer regarding what bar you are looking for to define as the right dose.
A very positive meeting with Jay and the team for liver.
Yes.
Yet another yet another example of.
Of.
The work that we're doing in the CNS.
And another example of.
What I think is 1 of the really differentiated aspects of our platform.
Both from a.
Functionality point of view and our ability to use.
Huidong Wang: You know, for example, the LISO GP3. Are we talking about over 50%?
Zinc finger transcription activators, and transcriptional rhopressa or <unk>.
2 to modify sales and a therapeutically relevant way.
Huidong Wang: reduction or even below the ERT level. So this is the first question. The second question is about the hemophilia A program. Just wondering, you know, if the two-year Factor A level has some decline, do you expect FD will ask for longer than one year follow-up for the phase three study? Good afternoon, Gina. So let me answer those questions in reverse order.
So we're really excited about that collaboration as well and we're looking forward to 2 of the output of <unk>.
Of those collaborations and.
Kind of building on the expertise and the CNS area that is supporting both of those programs. We are also advancing some internal.
Internal effort in the CNS and we will be talking about those when it's appropriate as well.
Alexander D. Macrae: Pfizer is handling the communication and the regulatory interactions around team affiliate, and I am so pleased that our baby is being looked after by Pfizer, and I know that they will do a great job in having those regulatory conversations. Around Fabri, Mark, do you want to discuss what we're looking for to determine success? Thank you. Sorry, apologies. The program goal is to, you know, look for a predictable, durable expression of the alpha galley enzymes. And then, you know, to see whether or not the resulting accumulation of the substrache of GV3 and a soluble derivative LisoGB3 goes down.
Got it so you've got 2 undisclosed neurology targets with Biogen, along with fiber to the opportunity of clean on fiber 1 tower the correct.
Correct correct got it thank you.
Welcome.
And for the last and final question.
From Ben Burnett of Stifel. Please go ahead.
Hi, This is Kelly breathe the on for Ben Burnett. Thanks for taking our question, where you kind of of <unk>.
Western around TX 200, and I was just wondering if you can elaborate on how the car is designed in and if you've disclosed the co stimulatory domain.
As well as what you expect the expansion kinetics to be in the transplant setting relative to what's been seen in <unk>. Thank you.
Jason We haven't said much on this can you give for a for a guy from you should count.
Yes so.
I am not sure if we've disclosed.
The construct for our core but.
Needless to say, we are leveraging the learnings from the oncology field.
And you.
The advancements that have been made in cell therapy and oncology is what we are building upon without that works.
Mark McClung: We've not commented on the amounts that we, that we're expecting to see. You know, as Sandy mentioned, we've dosed the first four patients. We're moving into screening for the third dose court, which is terrific, and hopefully we'll have an update for you by the end of the year in terms of when you might start seeing some of that data. I'm sorry, be pressing, just wondering. I understand you.
There would not be the car T Reg programs that we're advancing.
That being said there are some very different biology of work within regulatory T cells, and that's where the work that the team itself.
With the yourself team did and then since the acquisition the Sangamo team have been doing over the years to really understand.
On the optimal car construct and the optimal ways too.
To purify ourselves and expand ourselves in advance of of.
Of infusing the paper.
Yeah.
All really paying off because this is this is work that is specific to T. Reg.
Mark McClung: We've not commented on that. I mean, I know some of the others.
Mark McClung: Okay, that's fair. Thank you.
Huidong Wang: But, Gina, I want to strike a note of caution as you interpret the microbiotata. The reduction in GB3 will depend on where you start, and LIOG3 will depend on where you start. So if you have a high level of LISOGB3 and your compound is effective, you'll get a reduction. If your LISOGB3 is already at a low level due to ERT or addition, it's to cause a reduction. The dramatic graph that Avobi shows is an artifact of the patient that they recruited.
Anvita Gupta: And our next question is from Ritu Boral of Cowan. Please go ahead. Hey, I want to just follow up on Fabri again.
Okay, then I'll I'll disconnect. Thank you so much.
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Alexander D. Macrae: Can you, I know you can't really tell us about the safety findings, but can I ask what has been observed and learned in the cohorts to date and the preclinical, I guess, investigation to date? What does it tell you about the safety of the program? not just the standard A.B. Liver or complement issues but also cardiac safety within the Fabri population, just given competing programs, have shown signals. Is this something worth weeding patients out for? Or is this something that could be unique to various programs? And then I have a follow-up. So, let me answer that slightly tangentially.
Alexander D. Macrae: It's remarkable because we've now dosed AAP6 across a number of programs, and other than the occasional allergic response or the occasional ALT, considering how much virus we're giving, it is remarkably safe. Viruses are, the safety of them is very encouraging. The second thing is that we do not determine the safety ourselves but have a DSMB, which reviews all of the safety and allows us to carry on. I imagine that Freeline has a DSMB or some safety monitoring committee that has them that would have judged their cardiac events and given them advice on whether or not they could advance.
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Alexander D. Macrae: We have had a very clear unanimous response from her DSMB. Got it. That is very helpful. And then just because manufacturing buildout is prominently featured in the update, how should we be thinking about CAFX allocation for manufacturing buildout across the lead program?
Alexander D. Macrae: Our manufacturing build is going to be based on what they need across the different programs, and we will assess it in the next six months to 18 months.
Alexander D. Macrae: Got it. Oh, go ahead.
Alexander D. Macrae: I am so glad we invested in manufacturing 18 months, two years ago. They are on, they have completed AV manufacturing, and they're on track to do cell therapy manufacturing in Brisbane and Vaubon by the end of the year. And the reason I say that is because between idea and clinical material in manufacturing, it takes over a year, no matter who does it. And there is a queue now at the CMOs for manufacturing slots.
Alexander D. Macrae: But more importantly, if you look at what's happened with other ATV companies, it's the quality of manufacturing that is the most important regulatory discussion. And I feel by having our research group side by side with our manufacturing group to do process development, we have the best chance of the best product, and the process is the product. And so I think it was a wise investment we made.
Alexander D. Macrae: Got it. And then, Sandy, I just want to
Jason D. Fontenot: Sandy, I just want to triangulate your comments into the slides that were sent around today, especially in relation to the biogen collaboration. You mentioned progress on the biogen program with an undisclosed target. I want to make sure it's that, like on slide 22, you have alpha sinucleine, telopathies, and undisclosed. Are you referring specifically to that undisclosed neurology target, or should we be thinking about progress in one of the three? Jason, can you help me disentangle that?
Jason D. Fontenot: How many targets are on the go now in Bygium? We now have, Sorry about that. We now have four targets in the buyage, thrilled to see them progress, great to be working with a partner like by. I think that the fact that we are progressing on all of these targets is a reflection of how much confidence and team we have in that Sangamom team for these programs. So I'm really looking forward to when FIGE tell everyone more about the targets and about the work that we're appropriate will certainly publish the work.
Jason D. Fontenot: And Jason, before you go back on mute, we recently had a very positive meeting with Jay and the team from Nibber. Yes, you know, yet another example of the work that we're doing in the CNF. Another example of what I think is one of the really differentiated aspects of our class both from a functionality point of view and in our ability, Zingfinger transcriptional activators and transcriptional repressors, to modify cells in a therapy.
Jason D. Fontenot: So we're really excited about that collaboration as well, and we're looking forward to the output from both those collaborators and, you know, kind of building on expertise in the CNS area, supporting both of those programs. We also have an internal effort in, and we'll be talking. Got it. So you've got two undisclosed neurology targets with biogen, along with 502 alpha-synucline and 501 Correct. I got it. Thank you. And for the last and final question, from Ben Burnett, upspeople, please go ahead.
Jason D. Fontenot: Hi, this is Kaylee Braza on behalf of Ben Burnett. Thanks for taking our question. We just have a question about TX 200, and I was just wondering if you could elaborate on how the car is designed and if you've disclosed the co-stimilatory domain, as well as what do you expect the expansion to be?
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Kaylee Braza: Connect to be in the transcript setting relative to what's been seen in ecology. Thank you.
Jason D. Fontenot: Jason, we haven't said much about this. Can you give whatever guidance you can?
Jason D. Fontenot: Yeah, so, I am not sure if we've disclosed the construct for our car, but, needless to say, we are leveraging the learnings from oncology, and the advancements that have been made in cell therapy and oncology are what we're building upon. You know, without that work, there would not be the CAR-TREG programs that we're. But, being said, there is some very different biology within regulatory details. And that's where the work that the TXL team did, and then since the acquisition, the Sangamo team has been doing over the years to really understand the optimal car construct and the optimal ways to purify ourselves and expand ourselves in advance of infusing into the patient, that it's all really paying off because this is work that is specific to T-Regs, and there are things that were not obvious based on the oncology experience.
Jason D. Fontenot: And that deep understanding of the T-Reg biology biology is what we're bringing to bear on the TX-200 per. We're really excited to see you move forward. Thank you. I was wondering also if you would be able to give any details of when you expect to disclose the proof of conduct.
Jason D. Fontenot: when you expect
Jason D. Fontenot: I am very anxious. Let me help you with that one, Jason.
Alexander D. Macrae: Yeah, we haven't guided them, and we'll do that as soon as it's appropriate. It's a, you know, they, the first thing that we're testing is safety, obviously, and we have data available. We will certainly share it, but, Thank you. Thank you, everyone. At this point, I would like to turn it over to Aaron Pangeld, the head of corporate communications. Thank you once again for joining us today and for your questions. We look forward to keeping you updated on our future developments. And this includes today's conference call. Thank you, everyone, for your participation. You may now all disconnect. Thank you so much.
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Operator: Thank you. Thee Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, Bhopes.
Operator: Thank you. Thank you. Thank you. Thank you.
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