Q4 2022 Sangamo Therapeutics Inc Earnings Call
The conference will begin shortly to raising Malawi Johan during Q&A, you can dial star one one.
[music].
Yeah.
Good day, ladies and gentlemen, and thank you for standing by welcome to the Sangamo fourth quarter 2022 earnings Conference 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.
Ask a question during this session you will need to press star one one on your telephone keypad at this time I would like to turn the conference over to Mr. Luis Wilkie Ma'am. Please begin.
Thank you.
Good afternoon, I'm Louise locate vancomycin, Vice President of Investor Relations and corporate communications. Thank you for joining us on the call today.
On this call are several members of the Sangamo executive leadership team, including Sandy Macrae, Chief Executive Officer, Mark Mcclung, Chief Chief operating Officer.
Asia, Europe hopping, Chief Financial Officer, Jason <unk>, Chief Scientific Officer, Nathalie Dubois, Stringfellow, Chief Development Officer, Bettina Cockroft, Chief Medical Officer, and Anteroom Omar head of technical operations.
Slides from our corporate presentation can be found at our website sangamo com under the investors and media section of the events and presentations page.
This call includes forward looking statements regarding <unk> current expectations.
These statements include but are not limited to statements relating to the therapeutic and commercial potential of our product candidates the anticipated plans and timelines of Sangamo and our collaborators for initiating in conducting clinical trials screening and dosing patients presenting clinical data.
Advancement of our product candidates advancing preclinical programs to the clinic are investment focused on the sufficiency of our resources.
2023 financial guidance upcoming catalyst and guidance and other statements that are not historical facts actual results may differ materially from what we discussed today. These statements are subject to certain risks and uncertainties that are discussed in our filings with the SEC.
Forward looking statements made today are made as of the sites and we undertake no duty to update such information.
As required by law.
On this call we discuss a 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 Luis and good afternoon to everyone joining the call.
I am pleased to share today, the significant process, we have made over the last year and being potentially transformative medicines closer to patients that need the most and to compare outlook for the coming 12 months.
2022, with a European cogent clinical and non clinical milestones for <unk>.
We believe we became the first company stores, the Cuban with an engineered car T. Reg.
We establish a leadership position in fabry disease, we presented promising data in sickle cell disease, and with Pfizer, We announced the resumption of our phase III hemophilia a trial.
I'm thrilled with the updated fabry data from our phase one two star study.
At least today at the 19th annual World Symposium.
In addition to sharing updated biomarker biomarker data, we revealed the first kidney biopsy data from this study along with exciting SF 36 General health scores findings, which when taken together bring to point the potential for <unk> to become a truly compelling piece therapy.
Based on what we've seen in the competitive landscape. We truly believe we have potential best in class, leading gene therapy for this important indication.
Not only will take us through the details of this new data shortly.
I wanted to express how happy I am with the progress of the program, which I believe is a strong potential to bring relief to those suffering debilitating aspects of fabry disease.
We are well underway and dosing the first two cohorts of patients with <unk> 200, and our phase one two steadfast study and actually <unk> mismatched kidney transplant and we believe we remain in the lead in clinical progress amongst car T companies.
This study potentially paves the way for current projects and development as a proof of concept and demonstration of safety of car T regs in humans.
Our focus is advancing advancing this trial with urgency while maintaining patient safety.
So the team is actively working with the regulatory authorities to explore options to accelerate the dose escalation protocol, we look forward to sharing more information when available.
The team has also made significant headway in advancing our second wave of preclinical programs progressing our car T. Reg follow on indications in multiple sclerosis, and inflammatory bowel disease advancing our four wholly owned CNS epigenetic regulation programs.
Breaking new ground in delivery through AAV Capsid Engineering program.
And continuing to advance our zinc finger genomic engineering platform.
I am proud of the progress we've made this year, which is a testament to the hard work and dedication of our talented team members across the organization.
During 2022, we remain dedicated to advancing our pipeline and executing on our corporate strategy.
In this regard we are happy to add two new board members to our board of directors.
Colin brings with him over 30 years of leadership experience in the biotechnology industry, having led many important strategic and financing transactions.
According to <unk> has also joined us as brink to single her long experience in drug development and scientific strategy.
Looking to 2023.
The leadership team is fully focused on progressing our clinical programs and continue the transition to <unk> second we've pipeline carefully prioritizing our efforts under spend on cell therapy with a car T. Reg franchise, and an epigenetic regulation in the CNS through both our wholly owned and partnered programs.
We believe these prudent.
These are programs that will leverage <unk> core finger capabilities and deep experience in genomic medicines and has the potential to be differentiated.
Positively impacting patients with high unmet medical need at scale.
As we navigate these current market conditions, we fully understand the importance of using capital wisely and I want to reiterate the focus in <unk> with which we are making decisions. Both in terms of capital spending and also implementing thoughtful fundraising strategies with long term shareholder benefit in mind.
In this respect we are pleased to present competitive data from our phase one two precision study in sickle cell disease at the American Society of Hematology annual meeting in December last year.
We've also since made additional manufacturing improvements that we believe could further strengthen potential phase III data and reduced manufacturing costs. So important in this indication.
However, in today's environment, we must make difficult choices today, we are announcing the strategic decision to halt further material investments in phase III planning for <unk>.
Zero zero III sickle cell disease program importantly.
Very importantly, we did not meet this decision because of efficacy results are due to any safety concerns we have simply decided to redeploy our resources away from the asset and towards investments and a potential phase III trial for our Fabry program and efforts to accelerate our phase one two TX 200 program.
As we stated when the program unexpectedly transitioned back just last year, we remain committed to the patients and investigators involved in the phase one two precision one study and expect to complete the study using funds we have already committed but we will make new material investments in the program going forward, we're comparing commencing.
An active search for a partner who can progress this promising asset to a potential phase III clinical trial.
I'd now like to turn the call over to our head of development Natalie.
<unk> discussed the data from our clinical programs in more detail.
Okay.
Thank you Sandy and good afternoon to everyone on the call.
This afternoon, we announced updated data from our phase one two star study evaluating is around the teen Tivo positive back our SD <unk> 920 <unk>.
Gene therapy product candidate for the treatment of Fabry disease.
19 annual symposium.
As sandy outlined in his opening the data presented today support potential best in class product profile for <unk>.
<unk> 920 to treat patients suffering from diabetes.
As of November 15, 2022, supplemental cutoff date 13 patients across the dose escalation and dose expansion thesis exhibited <unk> Alpha Gal a activity sustained for over two years for the patient with the longest follow up.
All five patients from the dose escalation phase will begin to study an enzyme replacement therapy had been successfully with joined from EBIT.
Not required a resumption of yaqui treatment as of today.
Importantly, we now have a kidney biopsy data demonstrating evidence of substantial GBC reduction in the kidney at six months in a call it fort patient.
With reduced <unk> put a sight loss.
We have also observed statistically and clinically significant improvement in mean general health score as measured by the SF 36 General Health Survey.
Based on these collective data point, we truly believe <unk> has the potential to become a leading gene therapy for this important indication and we are actively preparing for a potential phase III trial, which we expect to begin in the second half of 2023.
Now digging into the data in a little more detail in the dose escalation phase all nine patients treated in the dose escalation phase across the four doses exhibited elevated alpha gal activity ranging from nearly fourfold to 67 fold of men normal sustained for over two years for the land.
This is treated patient.
Under 15, 2022 supplemental cutoff date.
As I outlined earlier, all five patients who started this study ONEOK was successfully withdrawn from the I T.
To demonstrate two processes.
The equal level of Alpha Gal, a activity following withdrawal and remain of CRT today for.
For naive and pseudo naive patients in the dose escalation stage the court patient exhibited significantly higher levels of Alpha Gal, a activity compared to those patients in lower dose cohort.
As of the <unk> in November 2022, supplemental cutoff date, the first three patients dose in the expansion stage at this five <unk> vg per kg dose exhibited a rapid increase in alpha Gal a activity following dosing sustained for up to 14 weeks.
At the last date of measurement.
First patient at increased two within normal range at four weeks of dosing.
The first female participants dosed in this study demonstrated a similar response profile to milk as the cut off date.
<unk> III is a fatty substance that accumulate in the sales of fabry disease patients and can result in damage to multiple organs, including the kidney heart and central nervous system. The kidney biopsy for patient line, we demonstrated high number of Tvs inclusion and high plasma Liza GBP three level at baseline.
<unk> exhibited an impressive 78% clearance between cushion per pay tubular capillary PTC from an average of $8 seven inclusion for PTC at baseline to one nine inclusion for PTC six months after dosing.
This assessment was made by two blinded pathology.
Independently score digital images of the section kidney from baseline and six months biopsy.
Weighted by a third independent pathology.
Addition, dissipation exhibited a 77% reduction in urinary prototype loss after six months the significant decrease in renal TBC inclusion and the reduction in year end prototyping all support a favorable impact on progression of fabry in the property and indicates the meaningful nature of this potential.
Eric.
But kidney biopsy for patient eight we exhibited a lower number of TBC inclusion and lower level of plasma <unk>. Upon baseline demonstrated staple PCT included six months photos post dosing. These patients also exhibited an impressive 97% reduction in urinary <unk>.
Last up to six months, which coupled with the significant increase in alpha Gal a activity along with reduction of Liza GPS III. After dosing provides evidence of a potentially favorable effect on fabry and it drops.
In addition, since <unk>.
In General health score for patients in the dose escalation stage from baseline at week 52 was statistically significant with a mean increase general health score of $19 six for context, the 3% to $5 <unk>.
The SF 36 core is the minimally clinically important difference.
With regard to license <unk> level for naive and switch a nice patient baseline level of Liza III.
We started high patient expense of 46% to 65% reduction in levels following treatment and continue to decrease for two patients until the data cutoff for.
For the first time in the study and with the highest dose of 54% reduction in plasma lies with GBP three level was observed by baseline levels started below 25 nanograms per mil.
For patients in the dose escalation phase began the study on ERP plus my life would be three level. Following EIT withdrawal remain within the range of levels and variability normally observed in patients treated with <unk> in this patient Alpha Gal a activity remained elevated and no patient experience symptoms.
Requiring the reception of <unk> as of today.
As of the October 20th 2022 cut off date SG nine <unk> was generally well tolerated in the 13 treated patient with no treatment related adverse events greater than a grade two and no treatment related serious adverse events.
No prophylactic corticosteroids or other immune modulating agents have been administered.
These data are being presented in more detail by one of our study investigators Dr.
Dr. Robert Hopkins This coming Friday February 24th during a session from eight to nine a M. Eastern time and doing a poster presentation from three to four P. M. Eastern time, we would encourage you to listen to the presentation of these data are also available on <unk> website website in the presentation page.
Since the October 20th 2022 kind of data we have dosed an additional four patients in the expansion phase to achieve a total of 17 patients dosed in total.
We have also withdrawn and additional two patients from <unk>.
A total of 20 sites are now active and recruiting progressing the study continue with additional male and female patients currently in screening.
In December one patient in the expansion phase extend a great three serious adverse event of shoulder.
And to supersede, which was deemed as possibly related to treatment the patient a step.
Since fully recover.
And the safety monitoring Committee has determined the study may proceed without modification.
Similar events have been observed in any of these 16 other patient dose in the study to date.
We continue to plan for a potential phase III trial with our strategy in the U S progressing alongside our EU strategy.
Trial is anticipated to commence in the second half of 2023 and dosing of the first patient could happen as early as the first part of 2024, depending on regulatory interactions.
A reminder, the expansion phase of the phase one two study for which we expect to complete dosing in 2023 is not expected to be a gating factor for the commencement of phase III.
Okay.
In the phase one two steadfast study our wholly owned TX 200 car T. Reg cell therapy candidate for the prevention of immune mediated rejection in HLA <unk> mismatch kidney transplantation from a living donor. The first two patient dose continued to do well the third patient received a kidney transplant.
And we have successfully manufactured that personalized TX 200 cell therapy and dosing is expected early in the second quarter of 2023. This will mark the completion of the first full cohort of the study.
Preparation for the second cohort is actively progressing the first session is expected to receive that kidney transplant shortly and manufacturing is in progress.
Dosing is anticipated this summer Adil.
Additional patient Prescreening and continue to enroll.
Sandy outlined progressing the study quickly but safely is our top priority as such we are discussing with regulatory option to accelerate the dose escalation scheme to find the optimal dose for efficacy.
Moving onto sickle cell in December we presented updated preliminary clinical data from the phase one two precision one study of <unk> <unk> three a zinc finger nuclease gene editing autologous cell therapy product candidate for the treatment of sickle cell disease at ash.
The data showed that total <unk> been and <unk> been asked levels were maintained up to 30 months for the longest treated patients and that <unk> continued to remain generally well tolerated across the five patient dose with no treatment related adverse events.
Importantly, this was the first opportunity to present data for that patient dosed with the product candidate manufactured.
Improved process at six months following treatment patient five exhibited fetal hemoglobin level of 45% and total <unk> of $12 four gram per deciliter, which is significantly greater than the level observed in patients dosed with the original manufacturing process.
Based on these results we believe the <unk> three is a competitive potential treatment as sandy indicated we have been working on further enable improvement to the phase III manufacturing process, which we believe at the potential to further improve the final product.
We're learning from which we are carrying across our T. Reg manufacturing efforts.
We have also progressed clinical and manufacturing activity in anticipation of dosing patients seven into phase one two study and have agreed the phase III trial design CMC package and other requirement with the FDA.
We are disappointed not to progress. This program further our south but are hopeful that we can find a potential collaboration partner who can advance this program into a potential phase III trial as we believe this therapy has strong potential to help improve patient lives.
Finally dosing progressed in the phase III assigned trial appear Uptoke Putin detailed pop up back our investigational gene therapy, we are developing with Pfizer for patients with moderate to severe to severe hemophilia a.
Pfizer expect dosing to support primary analysis to be complete by the end of the first quarter of 2023, Pfizer recently reiterated that this is one of the most promising assets and we look forward to a pivotal readout expected in the first half of 2024, along with the potential BLA submission that.
Pfizer is anticipating in the second half of 2024.
I will now turn the call over to our Chief financial officer, but future for an overview of the financial results Patricia.
Thank you Natalie and good afternoon, everyone. We are really pleased with our accomplishments for the year, including the promising data emerging from our Fabry program and the progress of our car T break in CNS epigenetic regulation programs.
We ended the year with approximately $308 million in cash cash equivalence and marketable securities, which represents a net decline of $157 million from the prior year.
This included $85 million of additional capital raises during 2022 through the issuance of equity under our at the market offering program.
During 2022, we invested our resources and progressing important clinical and non clinical milestones, while operating a focused and lean organization.
In these tough financial markets, we will continue to seek ways to streamline spend while advancing programs and thoughtfully rethink capital to create long term value for our shareholders.
Yeah.
Turning to our 2020 full year guidance.
We expect our full year non-GAAP operating expenses to be between approximately 210 5 million to $295 million.
This range excludes estimated noncash stock based compensation expense of approximately $35 million.
During 2020, we will continue to focus our resources on programs that we believe will create long term value for our business, including our clinical asset <unk> thousand 920, <unk> hundred and a preclinical car T Reg and P&L pipeline.
Additionally, about 8% of operating expenses.
<unk> towards partnership programs, which are reimbursed.
Detailed financial results are available in the press release issued today I will now turn the call back to Sandy for closing remarks. Thank you Patricia.
I'm incredibly proud of what the team has accomplished over the last year and I want to thank all of them for their continued commitment to our science and our mission.
As you heard today Sangamo is focused and disciplined on advancing near term clinical programs and achieving additional milestones.
In 2023, we expect to complete the dosing of all remaining patients in the expansion phase with <unk> phase one two study and to commence a phase III Fabry trial.
We expect to complete dosing of the first TX 200 cohort early in the second quarter of 2023 and commenced dosing in the second quarter. This summer.
We also expect to complete the phase 126, so started using funds we've already committed.
And we intend to make no further material investment, but to seek a potential collaboration partners.
And in the first half of 2024, we anticipate pfizer's pivotal readout in hemophilia, a with a BLA submission anticipated in the second half of 2022 for us.
As a reminder, this program could generate up to 240 million.
<unk> and remaining milestone payments from Pfizer and could provide us with royalties between 14% and 20% on future potential product sales subject to customary reductions.
We're also progressing our preclinical programs with pace and are excited by the data we've seen to date by the end of 'twenty. Three we expect her notes and review data from our wholly owned epigenetic regulation programs in the CNS and at the end of 'twenty four we anticipate submitting two new IND applications from our second.
<unk> car T Reg can CNS programs.
We will also continue to advance our AAV capsid delivery capabilities, which are increasingly attracting the interest of potential partners.
As always we are working diligently to bring to patients what we believe to be improved treatment options for disease.
Unmet medical need needs drive our work here and there.
It is our mission to bring cell therapies, and epigenetic regulation to people with her.
Orange of diseases.
So at this point, we'd like to open up for questions.
Operator, please open the line for questions.
Ladies and gentlemen, if you have a question or comment at this time. Please press star one one on your telephone keypad. If your question has been answered or you wish to remove yourself from the queue simply press the pound key.
Again.
Ask a question. Please press star one one on your telephone keypad.
Please standby, while we compile the Q&A roster.
Our first question or comment comes from the line of <unk> and column Mr. <unk>. Your line is open.
Hi, Hi, everyone. Good afternoon, thanks for taking the question.
They have asked me about your comments around.
Interaction.
As usual.
Good luck.
What are you looking.
For any particular, followed.
Can I can I can I interrupt you because we don't Miss the question. Your line is so liquid.
Garfield.
You can see.
Be clear.
Hang on.
Yes.
Sandy is that better.
Oh, that's so much better thanks, Okay apologies. So a couple of questions Sandy on your phase III plans and as usual my question well have three parts.
One can you comment on the.
How does criteria that you reported with your data today, there's some additional posters here at world on prototypes urea and is that sort of gaining steam.
As a biomarker of import in the disease and then further as we look at the expression curves on slide 15 is there any particular follow up for expression that you are waiting to achieve before you finalize your fee.
With redesigned with the agency and then I have a very quick follow up.
A question.
The first one is if I put a site jewelry and what does that mean, what do we think about it and then there's a second one question I'm going to pass on to naturally about the levels of expression and how long.
Alone be lost and are waiting for a specific time for to declare success is that correct.
And finalize the phase III design with the agency.
Well I think I can might be too.
Both of them so.
We're always looking for.
Markers of disease and ways to show the success of our program.
The put a site.
Fabry causes a potent cytosis, which meetings.
<unk> services with 500 of them per.
Per capsule.
Disengaged with the capsule and fall into the Euro Theyre terminally differentiated so once you're in the urine there there's no going back and there is no new ones created.
And you detect them in the Europe No. This is a technique that is.
Use has been quoted and referenced in another forms of renal disease, but as you say there is I think there's two posters at the world Symposium on this switch.
To.
Reflect the interest in this.
Our near term closer marker of success or not with treating the renal disease.
Diseases. Unfortunately in February it's very debilitating condition, we know disease causes heart disease.
Its terminal stage. So we were very pleased that both of these patients showed this effect, we are only doing biopsies and.
Puja site urine.
And patients are.
At the top dose and patients that are naive for pseudo naive because otherwise the results may not be interpretable. So there will be future patients in the expansion cohort that will be looking forward to share with you and then I'll let.
So the second one just for ease of time, you said this or is there some kind of length of treatment that we are waiting to be able to clear success, yes, no noise. The simple answer we feel the first patients for up to 26 months for the first two patients $26 25 months Theres no sorry.
Any change in them, we are absolutely confident that this is a very stable.
Therapy, and we're no collectible. In addition, we're collecting months and months of safety data that give us a chance to go back to the agency and show the new data we visited the agency last year I've got some really good feedback from them, but that was when we only had a few patients in the study now we have more <unk>.
Any more patients were up 17, I belief is number that have been treated.
Have the biopsy data, we have the SF 36, which I think is remarkably.
Positive and we have to put us sites in the urine and we have continuously.
Continuous expression I think the package is so much more compelling for us to have a very productive discussion with the agency.
Understood and my very quick follow up on the grade III SAE could you clarify what shoulder condition that was I missed it.
So I'll I'll answer that one quickly and then I promise not to Youll get the next part of your question.
Okay.
Basically the patient presented 14 days after dosing so a significant time with our FIFA shoulder pain he found us.
Sure.
Sugar and upper arms was was painful it was painful to move he had was admitted to hospital.
Four days of treatment in <unk>.
<unk> of observation in hospital treatment course of steroids. He was seen by Rheumatologists and neurologists, who never really put to the bottom part towards the the condition, which resolving.
Nicola and this opportunity is opposite.
It's where the tendon meets the the bone tendon from a muscle meat seafood and it's basically there's a whole series of kind of inflammatory muscle joint type things that cause and then the software but the most important thing is it was 14 days after treatment.
<unk> quickly on the patient went home and as well.
Thanks for taking all the questions.
Thank you. Thank you.
Our next question or comment comes from the line of Jan and Ju from Wells Fargo.
Your line is now open.
Thanks, very much for taking our question.
Congrats on the data.
At World.
So.
Couple of questions on the on the STAAR study data first.
Would you put the kidney biopsy data.
From the study into context.
E R T and Russell <unk>, what kind of effect.
What would be seen with those tend to kind of.
Modalities and also.
Another question.
Yes.
This data is patient eight had a goodwill balance put affect loss, but no reduction in GBS inclusions, how do you see.
See this.
Phenomenon.
And then I have a question on TX 200. Thanks.
Thank you for the question I'm going to pass this on to not place our head of development.
Hi, Thank you for the question so regarding the <unk> inclusion in the kidney.
It has been reported for <unk>.
Usually there is a.
Reduction of similar.
Percentage in.
In <unk> treated patients at six months or a year.
Not all patients respond to.
<unk> treatment and the TV III inclusion decrease is not.
There is a small percentage of the population that doesn't decrease <unk> inclusion.
So.
This is important to note in terms of comparison, but we feel that the data is very encouraging because we.
We have a really indication of a reduction in loss of for the site.
In terms of patient eight this is a difficult patient because not only these patient fabry disease, but he also has type type two diabetes.
Hypertension, which really can impact kidney health.
It is a little bit hard to interpret the <unk> inclusion in this patient and perhaps further time.
Would would show.
Further progress.
And just to add a little to that this patient would not be included in our phase III because the license <unk> start to slow.
We will have some kind of exclusion criteria that allows us to segment out patients with us and when we showed this to several of the investigators and renal experts. They were not surprised October . They said this happens and it is recognized across the other treatments.
Very helpful. TX 200.
You mentioned, you're exploring opportunity to accelerate in dose escalation with regulators.
Wondering whether that is a safety or efficacy.
Driven decision.
And also could you give us a sense of the dose since you mentioned you mentioned that you want to accelerate the escalation.
Is it possible to let us know.
Have a sense of the first dose and the second dose.
And also any clarity and visibility to timing for data initial data.
From this study thanks, So I'll take this one for you it's based on safety and practicality and the dose has been very well tolerated.
The trial is is a complex one because it pivots around the patients transplant.
This are to complete the trial and get through all the doses.
<unk>.
We haven't stated the number of cells that we give back but it really depends on the number of cells, we can get from the patient and manufacture and its low medium and high and this is.
This is somewhat of an arbitrary low bitumen Holly we feel that getting to the top dose as quickly as possible gives the best chance for us to see.
Our compelling results and also offers the best chance to the patient.
Got it and timing.
Data.
We will be collecting data throughout the year and we'll show the data as soon as we have a complete data package.
Got it great. Thanks for the color.
Thank you as always.
Thank you.
Our next question or comment comes from the line of Gregory Harrison from Bank of America Merrill Lynch. Mr. Harrison. Your line is now open hi, there. This is Mary Kate on for Greg. Thanks for taking my question just looking at the Fabry program here. So in the presentation. We see the expansion phase patients 11, and 12 is still at early stages of follow up at the cut off.
Maybe and Theyre also saw an ear to maybe when could we expect these patients to begin the ERP withdrawal process and could you talk about what factors go into making that decision. Thank you.
Not only can you do this and press your button.
Yes sure.
Patient 11, and 12, but R&D protection space I've been withdrawn from the active since the data cutoff.
So.
They're our CIP at this point I didn't get the end of your question.
Yes, so what factors go into making the withdrawal process decision.
Oh so in.
The expansion phase.
The investigator can.
Start with join me Archie as soon as.
Eight weeks after.
Gene therapy treatment and we've chosen chosen this because at eight weeks, we feel that we have.
Expression above normal level of Alpha Gal.
Ah patients treated thus far so we wanted to wait until we have.
Above.
At least normal level above normal level, which we see in all our patients in the initial phase we had to it was right for us to leave it to the investigators discretion, because they're obviously keep recruiting tool of both of their patients.
They sold that.
As each one so someone else taking a patient off the green much more competence.
No that five of them are often for a significant period of time. The investigators are comfortable with those codifying this and suggesting that we first look to take them off.
Weeks onwards.
We have an enormous amount to support from the investigators in the study and the number of patients coming in has increased sharply with the.
The recent data.
Great. Thank you so much for taking our questions.
Thank you. Our next question or comment comes from the line of Ben Burnett from Stifel. Mr. Burnett. Your line is now open.
Great can you guys hear me.
Yes, Sir very.
Very clearly.
Excellent.
I also had a question about the Fabry program <unk>.
To give a few few patients with cardiac involvement.
I guess first from the baseline data are you seeing any changes on cardiac parameters is that something you're able to monitor.
Not only can you tell us.
So we're looking at this space and we're not selected.
Based on their cardiac involvement there are selected based on the fact that their classic mail, we have a panel of mild moderate and.
CVR patient.
And we're monitoring that cardiac involvement as we go but we.
We haven't really.
<unk> disclosed anything yet on the contact data.
At this point, we have anecdotal reports from the investors from the investigators in these patients so their cardiac condition is stable and they're there Peter.
<unk> edema has reduced but not.
So thats part of the study wasn't didn't have the.
Sophisticated set up that you require for an accurate cardiac study, which is part of the reason that we're doing a cardiac cohort in the expansion phase.
We are we are interested by four pre lines said the agency.
The FDA was open to when they announced the clinical trial hold for their study they implied that the FDA was open to talking about kartik events, because it's a significant health risk for fabry patients.
With a result, showing we can have an effect in the kidney there is no doubt in my mind that we would also have an effect in the heart and we are open to understanding the root for.
For treatment in registration for Fabry disease.
Okay excellent that's helpful. I appreciate that and I also wanted to ask a question kind of on the heels of the last discussion point on on kind of.
Well physicians look at sort of gain confidence to wean people off of <unk> for the folks are on it and it really I guess once theyre off what variables do they look at when considering kind of the durability of effect and whether or not they need to restart enzyme replacement therapy and you showed some interesting SF 36 clinical <unk>.
Core data is that like a like how big of a piece of that.
Is that for physicians assessing durability.
Natalie why don't you if you take the first step patients back on yes. So so.
The pie know that patient very well they have regular visits and the decision to resume our T space really.
Not on biomarker, but how that discussion goes in terms of the health of the patient how the patients feel.
And.
So so far the patients are doing well as is demonstrated by our SF 36 analysis and Theres been no need for assumption of the <unk> team any of the patient that has been withdrawn thus far.
And I'm. So glad you asked where the SF 36, SF 36 is a real standard of general patient health invented first in the nineties are described person lantus.
I've been doing drug development for 25 years, and putting SF 36 into studies that have got trucks. It clearly work antihypertensive onto <unk>.
<unk> drugs and very rarely do you get a bulge in the SF 36, and therefore the change in result here is really quite remarkable and I think it's an important one for us to listen to I know the investigators is presenting on Friday was was very taken by this result.
I think Youre also.
<unk>, probably got a very good point that when the investigation asks a patient how do they feel off PRT.
The equivalent of the SF 36.
I guess still a positive patient feels we are delighted with this trial because it's both we have the biopsy result, we have the biomarker result, we have the physiology in the potus sites and know we have the patients seem to feel better and stuff package that I think is really compelling.
Awesome, Okay. That's super helpful and just one point of clarification I apologize if I missed it is the go forward dose for the phase III cohort four is that still being.
Is that still under consideration.
So we have chosen <unk> vg per case, either a final dose and that's what we're doing in the expansion cohort and Thats, what we will do in the phase III study.
Okay. Okay got it thanks, so much.
Youre welcome.
Thank you. Our next question or comment comes from the line of Gena Wang from Barclays. Your line is open.
I wanted to revisit patient eight when I look back apples data.
I would like to biopsy data at the baseline of the PTC GP suite inclusions also was in the low like three to 435 to four range, but they are reduction of course, that's one here with much higher <unk>, 87% to 100%. So here several questions here.
First should we expect further reduction beyond week 24.
And also second question is how do you see the PTC <unk> Cushing the relationship with potash sites.
And then lastly regarding the phase III trial design given.
Given the current data.
We expect to run an active control study of without an active control.
So gena. Thank you for your questions. So let me go through each one of them I feel as I recall had four patients initial biopsy from two they didn't show what happened with the other two.
We are only doing.
Two kidney biopsies at baseline and one at 24 weeks and we will never know that.
Patient happens with if they got to one year.
Think it's difficult to compare the absolute values between studies.
<unk>.
I have no idea if there.
How do they did there I assume.
How it was reported so I can only comment on my own study.
Im not I believe this is a complicated patient and I'll say it again this would not be in our phase III trial with the patient was us described.
I'm not claiming that it should level of GPS III at baseline as the competition, but it's generally for a patient that is naive to have such a little lives with GPS III.
Is unusual and is surprising.
No the.
<unk>.
The relationships with the relationship with prototypes. So the real effect of GPS III is not their deep position in these capillary says they're deep position in the prototypes and the reason that the pit.
The largest week of three independent pathologists to reap these studies in a very intense.
Well control and controlled manner.
It's easier to look for inclusions in capillary spend is within auto sites, but the but the reality is <unk> is the thing that goes wrong in fabry disease. It's the thing that it faces and pulls away from the.
The bowman's capsule, and then disappears into the year and if we could measure of prototype <unk> I'm sure that would be four people would want to do but it's a capability.
<unk> III is the agency.
Is it too and their original regulatory documents.
Okay, and a phase III trial design in the phase III and phase III I would be.
It would be unfair to you to give your plans for phase III, we spoke to the agency last year, but really good I mean really detailed feedback and a sense of where they want to dispute to go.
So we'll go back to them next quarter with the results of this study we have a plan we know.
Going we've been planning for this phase III for some time, we expect to initiate it at the end of the year and once we've been through the agency and got confirmation that they're comfortable with that we will share that data with you and the rest of the community.
Okay. Thank you.
Thank you.
Our next question or comment comes from the line of Luca <unk> from RBC.
Your line is open.
For taking our questions. This is Lisa on for Linda just a couple from me on the Baby program.
First on the General Health score data can you comment why their patients at six months did not have a statistical signal.
A significant improvement.
At 52 weeks they did I'm just wondering what changed in that time, so in that time period.
Also a quick.
Quick one on Friday, well, we also have additional biopsy data available to us and secondly, or thirdly, rather.
The phase III trial design.
Is it potential to use the earn part of sites as the primary endpoint or is it fair to assume that the renal GBP three biopsies.
Yes, that's the primary thanks for taking my question.
Thank you Lisa So let me do the first the SF 36, and I'll pass on to Natalie to do the others.
SF 36, an instrument that can only be administered so often.
And it's not surprising that for a condition like this week.
<unk> for the for the substance we produced from the kidney and then for it to have its effect on the Oregon. So that it will increase and improve with time. If you look at the literature SF 36 declines.
Dramatically will for years with with Fabry patients and there's there's a clear decline or for 10 to 15 years and then the final.
When they finally go into renal failure. It gets much worse. So I think it's it's not significant because the changes.
Screeches is it 12 months when it's at six months, but it's a.
So it's a really remarkable rise over time I'm sure you must agree.
Yes.
Grateful to see that.
I'll start out of there.
But maybe you can comment on whether or not anymore.
Our more kidney biopsy results at the end of this week.
Okay. So.
What we're presenting today is the kidney biopsy, we have thus far is a kidney biopsy and the protocol were only done for the.
Ah patients at the highest dose that we selected for expansion cohorts. So we have those are the two first about seen patient eight 9% to first patient at the high dose and this is what we'll have at this point in term of primary endpoint put aside being primary endpoint.
Even though there is more noise about put aside being much more.
Relevant to Fabry disease. This is not a.
Validated endpoint per FDA so.
It would be included.
Our endpoint, but.
Probably not a problem.
Primary endpoint.
Alright, that's helpful. Thanks for taking our question.
Yeah.
Thank you our next question or comment.
It comes from the line of Nicole <unk>.
From Truest Janina your line is open.
Thanks for taking my question.
Just.
A couple so first off on that Brian Congrats on all the progress.
Given that you have CFO jacky withdrawn patient how much time off CRT and how many patients in the target dose cohort this FDA, where clinicians need to feel comfortable.
With potentially viewing SG&A in 'twenty as a potential ERP replacement, assuming the target dose.
<unk>.
The primary endpoint and electrify story.
Lastly, can you take that one yes, so as you can see in our.
In the five patients that have been withdrawn in the dose escalation from the IP, we have really sustained super surgical level for quite a long time.
All of the patient.
Haven't had that discussion yet with the FDA and how long they would need to see for but for ERP patient to be us.
But we don't think it's the gating component of starting the phase III until you reminded me earlier today is that none of these patients at <unk> are on the $5 13 to one.
The dose escalation phase, we've just dosed, we've just withdrawn patients.
Who were on <unk> two patients and so we look forward to seeing what happens to their levels.
In future weeks or months.
But it is not a gating this is not a gating point to start phase three.
Got it and.
And just a quick one for TX 200.
Can you talk about what potentially might be a good bar for QA localization for immune tolerance and.
Should we expect much in the first dose cohort and of <unk>.
In other words like of the number of infused car T Reg cells how.
How much do you think you'll need for immune tolerance based on animal data and then do you expect like 30% of the infused T regs to be sufficient to be able to have two natural T. Reg.
Can you just talk a little bit about that in as well.
Timelines for data presentation. After the first dose cohort is completed.
So we haven't commented on the number of sales, but can I pass you onto bettina for the clinical question Bettina.
Yes, absolutely so in terms of the.
Cohort one patients.
If those two patients.
We are expecting to do.
The Q2.
Third and last patient in cohort, one following which we will.
Evaluate the data and we're actually in the process.
Manufacturing.
For the first patient in cohort two of whom we expect to close this summer.
And we have not guided us.
As to when we might be sharing data, we are making sure that we accumulate.
The data from these patients in.
Cohort two to then be able to share that data at an opportune moment.
Great. Thanks Katina.
Thank you again, ladies and gentlemen, if you have a question or comment at this time. Please press star one one on your telephone keypad. Our next question or comment comes from the line of Mary Raycroft from Jefferies.
Mr. <unk> your line is open.
Great. Thank you and congrats on the update.
I was going to ask a question about beverage U for the PTC GB three inclusion data when considering the types of patients that you would enroll into a phase III can you talk about what you would expect for a phase III with the proportion of patients who would show a decrease in GB three inclusions overtime versus stable <unk> III inclusion.
And what would you expect in untreated or our control patients.
Mary. Thank you for your question that's why we're looking forward to seeing the the other.
<unk> biopsy switch for them that we would hope to reduce <unk> three in patients similar to patient nine.
We believe that patient eight as a note player in an exception.
Got it okay, Okay and.
For the sickle cell disease phase III CMC and other requirements with FDA can you talk more about what exactly you are aligned on and can you clarify if the regulatory minutes will enable a partner to move right into a phase III or is there still some work that needs to be done with that with regulatory discussions.
Natalie.
Yes. Thank you. So we just had a meeting with the FDA, where we will review our phase III clinical plan and agreed on.
Moving how to move forward.
And we also review our manufacturing strategy and we agreed on a plan for it so we think that.
If we find a partner that partner could.
Potentially be in phase III.
At the beginning of 2023.
Got it.
[laughter], Okay. Thank you very much for taking my questions.
Youre welcome.
Thank you I'm showing no additional questions in the queue at this time I would like to turn the conference back over to management for any closing remarks.
Thank you once again for joining us today and for your questions. As a reminder, you can access the earnings release and presentation on the Investor Relations section of the Sangamo website, we look forward to keeping updated on our future developments. Thank you.
Ladies and gentlemen, thank you for participating in today's conference. This concludes the program you may now disconnect everyone have a wonderful day speakers standby.
The conference will begin shortly to raise and lower Johan during Q&A, you can dial star one one.
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