Q4 2020 Sangamo Therapeutics Inc Earnings Call
[music].
Ladies and gentlemen, and today's conference scheduled to begin shortly please continue to standby and thank you for your patience.
Operator: Ladies and gentlemen, today's conference is scheduled to begin shortly; please continue to stand by, and thank you for your patience.
BF-WATCH TV: BF-WATCH TV 2021
Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Sangamo fourth quarter and full year 2020 conference call. At this time, all lines are in a listen-only mode.
[music].
Ladies and gentlemen, thank you for standing by and welcome to the Sangamo fourth quarter and full year 2020 conference call. At this time all participants lines are in a listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question during the session you'll need the press star one on your telephone please be advised of today's.
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you'll need to press star 1 on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Ms. Erin Feingold, head of corporate communications. Please go ahead, Ms. Feingold.
Conference is being recorded.
I would now like the hand, the conference over to your Speaker, Ms Air and Feingold head of corporate Communications. Please go ahead of them.
Good afternoon, and thank you for joining us today.
Erin 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 Macrae, Chief Executive Officer; and Mark McClung, Chief Business Officer. Jason Fontenot, 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.
With me. This afternoon on this call are suffer all the numbers of the Sangamo and executive leadership team, including Sandy Macrae, Chief Executive Officer, Mark Mcclung, Chief Business Officer, Jason talk now Chief Scientific Officer, Rob shot head of development.
Bettina Cockroft Chief Medical Officer.
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.
Erin Feingold: This call includes forward-looking statements regarding Sangamo's current expectations. These statements include, but are not limited to, statements relating to plans and timelines for Sangamo and our collaborators to conduct clinical trials and present clinical data and the potential for these data to demonstrate clinical benefit to patients, plans and timelines for bringing additional in-house manufacturing facilities online, our expectations regarding our financial performance and resources, and other statements that are not historical facts. However, actual results may differ substantially from what we discussed today.
This call includes forward looking statements regarding Sangamo current expectations. These.
These statements include but are not limited to statements relating to you.
Plans and timelines for Sangamo and our collaborators to conduct of clinical trials and present clinical data and the potential for these data to demonstrate clinical benefit the patient.
Plans and timelines for bringing additional in house manufacturing facility on line.
Our expectations regarding our financial performance and Heath.
And other statements that are not historical fact.
Actual results may differ substantially from what we discuss today.
Erin Feingold: In addition, these statements are not guarantees of future performance and are subject to certain risks and uncertainties that are discussed in documents that we file with the Securities and Exchange Commission, specifically in our annual report on Form 10-K for the fiscal year ended December 31, 2020. The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information except as required under applicable law. On this call, we discuss a non-GAAP financial measure.
In addition, these statements are not guarantees of future performance and are subject to certain risks and uncertainties that are discussed and documents that we file with the securities and Exchange Commission.
Typically and our annual report on form 10-K for the fiscal year ended December 31st 'twenty and 'twenty.
The forward looking statements stated today are made as of the seat and we undertake no duty to update such information, except as required under applicable law.
On this call, we discussed and non-GAAP financial measure.
Erin Feingold: We believe this measure is helpful in understanding our past financial performance and our potential future results. However, this is not meant to be considered in isolation or as a substitute for the Comparable Gap Measure. The comparable GAP measure and reconciliations of GAP to the non-GAP measure discussed on this call are included 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.
We believe this measure is helpful in understanding our past financial performance and our potential future results.
This is not meant to be considered and isolation, whereas the substitute for the comparable GAAP measure the.
The comparable GAAP measures and reconciliations of GAAP to the non-GAAP measure and discussed on this call are included 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.
Alexander D. Macrae: Thank you, Aaron, and good afternoon to everyone on the call. I'd like to start by saying just how pleased we are with Sangamo's progress in 2020, despite all of the challenges of the pandemic. We executed on moving product candidates forward in the clinic. We executed on strengthening our manufacturing infrastructure and bolstered our strong cash position to execute on our therapeutic pipeline. Specifically, we initiated our Phase 1-2 study of our wholly-owned product candidate treating Fabry disease and, together with our partner Pfizer, the Phase 3 trial of our product candidate treating haemophilia A. We entered into transformational neuroscience collaborations with Biogen and Novartis to tackle challenging diseases such as Alzheimer's disease, Parkinson's disease, and autism spectrum disorder.
Thank you Erin and good afternoon to everyone on the call.
I'd like to start by saying just true police, we aren't goosing and was progression and 'twenty 'twenty. Despite all of the challenges of the pandemic.
We executed on the two product candidates forward in the clinic.
We executed on strengthening our manufacturing infrastructure and bolstered our strong cash position.
Executing on our therapeutic pipeline specifically.
We initiated our phase one two study of our wholly owned product candidates treating tunbridge disease, and together with our partner Pfizer the.
The phase III trial of our product candidate and treating Hemophilia Inc.
We entered into a transformational neuroscience collaborations with biogen and the boxes to tackle challenging diseases, such as Alzheimer's disease, Parkinson's disease and.
Autism spectrum disorder.
We brought in house manufacturing capabilities on line and our Brisbane, California headquarters. This is a tremendous achievement and under and you condition and bringing our facility on line. During COVID-19, pandemic was particularly impressive and a testament to our dedicated manufacturing team.
Alexander D. Macrae: We brought in-house AAV manufacturing capabilities online at our Brisbane, California headquarters. This is a tremendous achievement under any condition, and bringing our facility online during the COVID-19 pandemic was particularly impressive and a testament to our dedicated manufacturing team. Our research engine was also highly productive, advancing our wholly owned TX200 CAR-T-REG cell therapy product candidate and all of our partner programs. And then we built a strong cash position, primarily through upfront payments from our collaborations, and finished the year 2020 with $692 million in cash, cash equivalents, and marketable securities.
Our research engine was also highly productive advancing our wholly on TX 200 car T Reg cell therapy product candidate.
And all of the partnered programs.
And then we built a strong cash position.
Or at least to upfront payments from our collaborations and.
And finished the year 2020, with $692 million and cash cash equivalents and marketable securities.
Looking ahead to 2021 were focused on further unlocking sangamo spinal used through clinical execution.
Alexander D. Macrae: Looking ahead to 2021, we're focused on further unlocking Sangamo's value through clinical execution. For our wholly owned programs, we expect to continue to enroll patients into our Phase 1-2 FABRI study and present initial data by the end of 2021. We also anticipate initiating our Phase 1-2 kidney transplant rejection study in the second half of the year. And lastly, we expect to continue to advance our proprietary manufacturing capabilities and bring our cell therapy manufacturing facilities online by the end of 2021. We believe that in-house manufacturing capabilities can provide a competitive advantage with greater flexibility and quality control.
For our wholly owned programs, we expect to continue the to enroll patients and turf Steve wanted to Fabry study and presented initial data by the end of 'twenty one.
We also anticipate initiating a phase one two kidney transplant rejection study and the second half of the year.
And lastly, we expect to continue to advance of proprietary manufacturing capabilities and bring their cell therapy manufacturing facilities online by the end of 2021.
We believe the in house manufacturing capabilities can provide the competitive advantage with greater flexibility.
And the quality control.
Also in 'twenty and 'twenty, one we expect continued momentum and our partner programs. For example, Pfizer expects continued enrolment tenor of phase III hemophilia, a fine trial with an expected presentation of the true data in 2022.
Alexander D. Macrae: Also, in 2021, we expect continued momentum in our partner programs. For example, Pfizer expects continued enrollment in our Phase 3 Haemophilia A affine trial with an expected presentation of pivotal data in 2022. Additionally, Pfizer expects another update from the ongoing Phase 1-2 Ultra study within the next year. Additionally, our partner, KITE, expects the initiation of a clinical study of its anti-CD19 CAR-T cell therapy by the end of 2021. Lastly...
Additionally, Pfizer expense and another one day.
From the ongoing phase one two ultra study within the next year.
Our partner Kite expects the initiation of a clinical study.
And T C D and 19 car T cell therapy by the end of 'twenty one.
Lastly, we anticipate presentation of the initial data at the end of 2021 from our phase one two study if all the aging of our investigation sickle cell disease product kind of developed with our collaborator Sanofi.
Alexander D. Macrae: we anticipate
Alexander D. Macrae: We anticipate presentation of initial data by the end of 2021 from our Phase 1-2 study evaluating our investigational sickle cell disease product candidate developed with our collaborator Sanofi, and then we also anticipate an update on our beta thalassemia program by the end of 2021.
And then we also anticipate and update on our beta thalassemia program by the end of 'twenty one.
Yeah.
Alexander D. Macrae: I would like to conclude my opening remarks by introducing the newest member of our executive team who joins us on the call today. Rob Schott, our Head of Development. Rob's leadership capabilities and drug development experience will help Sangamo advance our late-stage pipeline and prioritise our development efforts on programs with the highest likelihood of success and impact. He will be an instrumental leader during a year in which we anticipate several significant clinical milestones.
I would like to conclude my opening remarks by introducing the newest member of the executive team, who joins us on the cold Steve Robb.
<unk> shown our head of development.
<unk> leadership capabilities and drug development experience will help sangamo with funds of our late stage pipeline and prioritize our development efforts on programs with the highest likelihood of success and impact it.
He will be and instrument two liter during a year and which we anticipate several significant clinical milestones.
Alexander D. Macrae: Effective at the beginning of this year, we also promoted Jason Fontenot to Chief Scientific Officer. Jason has contributed significantly to Sangamo in his former role as head of cell therapy and in his latest role as acting interim head of research. This new role enables Jason to continue building our heritage in genomics and cellular science. I'm very excited by the partnership between Jason and the research team and Rob and the development team, which is designed to advance our differentiated technology to support a robust clinical pipeline.
The bigger.
And this year, we also promoted Jason Jason Continental to Chief Scientific Officer.
Jason has contributed significantly to cycle one of his former role of sides of cell therapy, and then as leases roll and.
From head of research.
This new rule and Naples, Jason to continue building, our heritage and genomic and cellular of science.
I'm very excited by the partnership between Jason and the research team and roll up and the development team, which is designed to advance our differentiated technology to support our robust clinical and like what.
Before I turn the call over to the team I'd like to acknowledge the hard work and dedication of all of the Sangamo of employees, who can mentor loves to keep of research engine running and those who progressed our business working from home.
Alexander D. Macrae: Before I turn the call over to the team, I'd like to acknowledge the hard work and dedication of all the Sangamo employees who came into our labs to keep our research engine running and those who progressed our business working from home. These were challenging circumstances. I am so proud of the team's achievement. With that, I will turn the call over to our Chief Medical Officer, Bettina, who will provide additional details on our clinical accomplishments. Bettina.
These are challenging circumstances I am so proud of the team's achievements.
With that I will turn the call over to our Chief Medical Officer, Patina, who will provide additional details on the clinical accomplishments.
The team.
Good afternoon.
Bettina M. Cockroft: Good afternoon, As Sandy mentioned, we're very pleased with our clinical momentum in 2020, which propels us into 2021 with multiple potential clinical catalysts. At ASH 2020, we and Pfizer announced updated Phase 1-2 results from the ULTIV study showing sustained factor VIII activity levels in the 3E13 vector genomes per kilogram high-dose cohort through one year following gyroptocogene cytoparvovec gene therapy treating haemophilia A. The results for the high-dose cohort showed that, as of the cut-off date, Gyroptochogene Fidel Barbovec was generally well tolerated.
Sandy mentioned, we're very pleased with our clinical momentum from 2020, which propels us into 'twenty and 'twenty, one with multiple potential.
On it.
I asked 'twenty and 'twenty, we and Pfizer and now updated phase one two the results from the Alta study showing the same factory activity levels and the three E T X the gene.
<unk> per kilogram high dose cohort through one year following.
He took over the Jeep.
G.
Treating hemophilia a.
The results for the high dose cohort showed that as of the cutoff date.
G roster of gene people part of it.
<unk> was generally well tolerated.
So the states such as activity was achieved and we Tonight.
Bettina M. Cockroft: Steady State Factor VIII activity was achieved by Week 9. Mean and median factor VIII activity remained in the therapeutic range through week 52 for all size patients and through the longest available follow-up of 82 weeks for the longest treated patient. Specifically, from week 9 to 52, group median factor VIII activity was 56.9%, and group geometric mean factor VIII activity was 70.4% by biochromogenic assay. There were no bleeding events in the first year and only one target joint bleed during the second year following vector infusion.
Mean, and median fluctuate activity remained and the therapeutic range through week 52, four or five patients on.
And through the longest available follow up of 82 weeks for the longest treated patients.
Statistically from week nine to 52 group median factories activity was $56 nine.
And group geometric mean fluctuate and activity with 74% biopolymer genetic assay.
There were no bleeding events and the third year and only one target joint bleeds and the second year of Halloween.
Yeah.
It is important to note that these results are reflective of the five patients followed for less from two years.
Bettina M. Cockroft: It is important to note that these results are reflective of five patients followed for less than two years. It is also important that we continue to watch these patients over time and understand the potential of this therapy when we see a larger patient sample in the Phase III assigned study, which Pfizer continues to enroll. Regarding our FABRI program, we have dosed the first three patients in the Phase 1-2 STAR study evaluating ST920 and FABRI disease.
It is also important we continue to watch the patients over time.
When we see the largest patients from the phase III of fine.
Which pfizer continues to enroll.
Regarding our Fabry program, we have done.
The three patients and the phase one to start on study evaluating the 920 and fabry disease.
Following last year's dosing of the first two patients establishing the first cohort.
Bettina M. Cockroft: Following last year's dosing of the first two patients, establishing the first cohort, earlier this month, we dosed the first patient in the second dose cohort. The START study is evaluating the safety and tolerability of ST920 in plastic or Fabry patients 18 years and older, and it includes all comers, those on enzyme replacement therapy or ERT, ERT-nave patients, or ERT-pseudo Key secondary efficacy measures in this trial include alpha-GalA activity and assessment of Gb3 and lyso-Gb3 levels.
This month, we dosed the first patient and the second dose cohort.
The start study is evaluating the safety and Tolerability of NSC, 920, and plus the fabry patients 18 years and older.
And include all comers.
Enzyme replacement therapy or Yaqui.
Yeah T naive patients on.
And our teams to the patients who have not received TRT treatment and the price of six months.
Key secondary efficacy measures in this trial include Alpha Gal a activity and.
Assessment of GBP and length of GBP level.
We expect to present initial fabry clinical data by the end of 'twenty 'twenty. One after we have identified a dose cohort expansion.
Bettina M. Cockroft: We expect to present initial Fabry clinical data by the end of 2021 after we have identified adults for cohort expansion. We expect the initial readout to include safety and tolerability measures, as well as biochemical data such as enzyme and substrate levels. We do not expect the initial readout to include kidney biopsy data, which will be collected at a later date.
We expect the initial readouts to include safety and Tolerability measures.
And that's why with biochemical data such as enzyme and substrate levels.
We do not expect the initial readout to include kidney biopsy data, which will be collected at the later date.
We look forward and continuing to keep you informed on our progress and this program.
Marc: We look forward to continuing to keep you informed on our progress in this program. I will now turn the call over to Marc for an overview of the financial results.
I will now turn the call over to Mark for an overview of the financial results.
Art.
Thank you Bettina and good afternoon, everyone and we're pleased to share our financial results for the fourth quarter and full year 2020.
Marc: Thank you, Bettina, and good afternoon, everyone.
Marc: We're pleased to share our financial results for the fourth quarter and full year 2020. Beginning with our fourth quarter results, we reported a net loss of $40.7 million, or $0.29 per share, compared to a net income of $4.5 million, or $0.04 per share, for the same period in 2019. Total revenues were $25.8 million, compared with $54.9 million for the same period in 2019. In 2019, we achieved milestones in the fourth quarter under our collaboration agreements, which included $25 million for the completion of the IND transfer to hemophilia A and 7.5 million from Spinel for dosing the first patient in our sickle cell disease phase 1-2 clinical study.
Beginning with our fourth quarter results the.
The reported the net loss of $40 7 million or <unk> 29 per share compared to net income of $4 5 million or four cents per share for the same period and 2019.
Total revenues were $25 8 million compared with $54 9 million for the same period and 2019.
And 2019, we achieved milestones and the fourth quarter under our collaboration agreements, which included 25 million per the completion of the R&D transfer with the hemophilia a.
And seven 5 million from Sanofi producing.
The dosing the first patient and our sickle cell disease phase, one and two clinical study the.
Marc: The expected decrease in revenues is primarily due to these milestone achievements. As a reminder, we also earned $35 million in milestones from Pfizer, as expected, in the third quarter of 2020, related firstly to the dosing of the participants in our phase three affine study, our gene therapy program in hemophilia A, and second, for completing our research activities in collaboration to develop genome regulation therapies for the treatment of C9-ORF-related ALS, non-GOP total operating expenses, which
The expected decrease in revenues is primarily due to these milestone achievements.
As a reminder, we all share and 30.
$35 million of milestones from Pfizer as.
As expected and the third quarter of 2020.
The weighted firstly to the dosing of the participants and our phase III of Fine study.
The gene therapy program from here.
The only a and second for completing our research activities and.
And collaboration to develop genome regulation therapies for the treatment of C&I and off related.
Alice.
Non-GAAP total operating expenses, which exclude noncash stock based compensation expense for $62 6 million and the fourth quarter compared to $48 2 million and the same period and 2019 the increase.
Operator: Who did it?
Marc: non-cash stock-based compensation expense of $62.6 million in the fourth quarter compared to $48.2 million in the same period in 2019. The increase in operating expenses was due primarily to headcount growth and facilities expansion to support the advancement of our clinical trials and manufacturing capabilities.
And operating expenses was due primarily to headcount growth and facilities expansion to support the advancement of our clinical trials and manufacturing capabilities.
Turning to the full year of 2020 results for 2020, we reported net loss of $121 1 million or <unk> 90 per share compared to a net loss of $95 4 million or <unk> 85 per share on 2019.
Marc: Turning to the full year 2020 results, for 2020, we reported a net loss of $121.1 million, or $0.90 per share, compared to a net loss of $95.4 million, or $0.85 per share, in 2019. Revenues were $118.2 million in 2020 compared to $102.4 million in 2019. The increase in revenues was primarily due to the recognition of upfront licensing fees under the Biogen and Novartis collaboration agreements entered into in 2020. The increase was partially offset by a decrease in revenues from our Hemophilia A collaboration agreement with Pfizer following the IND transfer in December 2019, non-gap total operating income
Revenues were $118 2.002 million 20.
Compared to 102 4.002 million 19.
The increase in revenues was primarily due to the recognition of upfront licensing fees under the Biogen and Novartis collaboration agreements entered into in 2020.
The increase was partially offset by a decrease in revenues from our hemophilia a collaboration agreement with Pfizer following the IMD transfer and December 2019.
Non-GAAP total operating expenses were $222 million compared to $188 3.002 million 19.
The increase in operating expenses was primarily due to headcount growth and facilities expansion.
As mentioned in the fourth quarter operating expense discussion these increases reflect the advancement of our clinical trials and manufacturing capabilities.
This increase was partially offset by a decrease in travel and corporate costs and 2020 of rising to the COVID-19 pinned on it.
Moving to the balance sheet, we ended the quarter with approximately $692 million of cash cash equivalents of marketable securities.
Marc: expenses were $222 million compared to $188.3 million in 2019. The increase in operating expenses was primarily due to headcount growth and facilities expansion. As mentioned in the fourth quarter operating expense discussion, these increases reflect the advancement of our clinical trials and manufacturing capabilities. This increase was partially offset by a decrease in travel and corporate costs in 2020 arising from the COVID-19 pandemic.
In addition to this balance in 2021, we've received net proceeds of about $15 7 million from the sale of our common stock.
Through February of the 19th 2021 under our aftermarket offering program that we established in 2020.
We believe our balance sheet remains strong and will allow us to reach several important R&D.
Millstones, including potential filing of our BLA for hemophilia a.
And potentially true gets reviewed and possible approval.
Turning to 2021 full year guidance, we expect non-GAAP operating expenses, which excludes estimated noncash stock based compensation expense of about $30 million to be in the range of approximately 255 million to $275 million.
Alexander D. Macrae: Moving to the balance sheet, we ended the quarter with approximately $692 million in cash, cash equivalents, and marketable securities. In addition to this balance in 2021, we have received net proceeds of about $15.7 million from the sale of our common stock through February the 19th, 2021, under our at the market offering program that we established in 2020. We believe our balance sheet remains strong and will allow us to reach several important R&D milestones, including the potential filing of our BLA for hemophilia A and, potentially, through its review and possible approval.
I will now turn it back to sandy for closing remarks.
Thank you Mark.
I'd like to conclude by saying that we're very pleased with the progress made in 'twenty, and 'twenty and where we find ourselves as a company and 'twenty one.
With the building momentum with our clinical execution research engine and in house manufacturing capabilities.
And our strong balance sheet enables us to advance our R&D pipeline.
We are and a compelling position to achieve several important milestones and catalysts this year.
And we look forward to updating you.
Operator, please open the line for questions.
Thank you and ladies and gentleman, who asked the question just press star one on your telephone keypad. So we do all of your question simply press the pound key.
Alexander D. Macrae: Turning to 2021 full-year guidance, we expect non-GAS operating expenses, which excludes estimated non-cash stock-based compensation expense of about $30 million, to be in the range of approximately $255 million to $275 million. I'll now turn it back to Sandy for closing remarks.
One moment, while we compile the Q&A roster.
Our first question is from Maury Raycroft with Jefferies. Your question. Please.
Hi, everyone and congrats on the progress and thank you for taking my questions.
First one is on S. T 920, and fabry so for the patients you've enrolled and treated can you provide any additional perspective on the patient status and their backgrounds too. So I guess are they are key experience naive or pseudo naive and anything else you can say about the patient.
Operator: Thank you again. I'd like to conclude by saying that we're very pleased with the progress made in 2020 and where we find ourselves as a company in 21. We're building momentum with our clinical execution, research engine, and in-house manufacturing capability, and our strong balance sheet enables us to advance our R&D pipeline. We are in a compelling position to achieve several important milestones and catalysts this year, and we look forward to updating you. Operator. Please open the line for questions.
So Laurie we're being very careful to.
Steve.
Often debt we wouldn't.
If the results of the study or the characteristics and to the end of the study because I think that's going to be easier for you to better and new product casinos or anything that we can see the patient sort of well.
We thank you sounded sort of the pace and are well, we have been roles and assignments.
Maurice Thomas Raycroft: Thank you. And ladies and gentlemen, to ask a question, just press star 1 on your telephone keypad. To withdraw your question, simply press the pound key. One moment while we compile the Q&A roster. Our first question is from Maurice Raycroft with Jefferies. Your question, please.
The patients dosed three patients.
The cohort two enrollment is ongoing the subsequent patients on.
And as Sandy mentioned, we expect there will be share towards the end of 'twenty and 'twenty. After we've completed the dose ex.
Maurice Thomas Raycroft: Hi everyone, congrats on the progress and thank you for taking my question. The first one is on ST920 in Fabry.
Escalation part.
Got it okay.
Thank you and then second question is on the kite <unk>, seven and TX 200 cell therapy programs.
Alexander D. Macrae: So for the patients you've enrolled and treated, can you provide any additional perspective on the patient's status and their backgrounds, too? So I guess are they ART experienced, naive, or pseudo-naive? Anything else you could say about the patients?
Wonder if you can comment on whether there are synergies between these two programs from manufacturing standpoint, and is there any additional insight you can provide into gating factors prior to starting the studies for both for one or both of the programs.
Well, that's an interesting question.
So both are progressing.
Bettina M. Cockroft: So Maury, we're being very careful to just stay, often saying we won't give the results of the study or the characteristics until the end of the study because I think that's going to be easier for you to better know our product. Bettina, is there anything that we can say? Are the patients all well?
Gilead of God.
They will be moving over to IMT and.
And to the clinic very soon with the.
And the car.
Car T and.
And for the T. Reg program, we have said that we will dose of patient in the second half of this year and are moving forward with.
Maurice Thomas Raycroft: So the patients are well, we have enrolled, as I mentioned, three patients. So Cohort 2 enrollment is ongoing with subsequent patients, and as Sandy mentioned, we expect data to be shared toward the end of 2020 after we've completed the dose escalation part.
Great momentum to there.
You're back growth question is more interesting it's about what do we learn on.
And there is learnings across the Jason I Wonder if you could comment about the difference between car T and car T Reg and the learnings and and what we're trying to do.
Sure.
Maurice Thomas Raycroft: Got it. OK. Thank you.
Both of these programs are very exciting.
Maurice Thomas Raycroft: And then my second question is about the CHITE-037 and TX200 cell therapy programs. Just wondering if there are synergies between these two programs from a manufacturing standpoint, and is there any additional insight you can provide into gating factors prior to starting the studies for one or both of the programs?
We're excited and working with our partners and height and.
We're also tremendously excited about our engineered T Reg program.
And there are certainly synergies around our understanding of local site engineering and the use of <unk>.
And the platform in both T cells and the.
Type program and and T Reg.
For our program. So I would say that's where the biggest synergies are as you probably know.
Jason D. Fontenot: Your background question is more interesting. It's about what we learn, and there are learnings across it. Jason, I wonder if you can comment about the difference between CAR-T and CAR-T-REC and the learnings in what we're trying to do.
Is.
It's doing the manufacturing for their product and we.
We own the manufacturing for our T. Reg program and there are some real differences between T Reg manufacturing compared to.
Jason D. Fontenot: Sure. Both of these programs are very exciting. You know, we're excited to be working with our partners at KITE, and we're also, you know, tremendously excited about our Engineer T-REG program. There are certainly synergies around our understanding of local site engineering and of our ThinkFinger platform in both T-Cells in the KITE program and in T-REG for our program. So I would say that's where the biggest synergies are.
On.
Two effector T cell manufacturing per car, Ts and oncology and Thats, where we really heavily invested and I think.
Our work is paying off and.
And in building the process development and manufacturing or for regulatory T cells.
Lots of nuance and.
And it can be quite different from from party, but is a critical part of our program and why we're so inside of them.
Marc: As you probably know, KITE is doing the manufacturing for their product, and we own the manufacturing for our T-REG program. And there are some real differences between T-REG manufacturing compared to effector T-cell manufacturing for CAR-Ts and oncology. And that's where, you know, we've really heavily invested, and I think our work is paying off in building the process development and manufacturing for regulatory T-cells, which has lots of nuance and can be quite different from CAR-T, but it's a critical part of our program and why we're so excited about it.
Mark can you touch on the manufacturing strategy and what we're building out for the.
So it was on manufacturing.
Yes, so we.
We believe that our manufacturing capability can provide a competitive advantage.
So we're building a balance the necessary capacity to achieve our in house manufacturing.
As well as securing access through our partnerships with our contract manufacturers.
We're investing and manufacturing process and analytics and.
At the beginning to lay the foundation for developing and strong supply chain.
Great well, thanks for all of the perspective of it and I'll hop back in the queue.
Thanks Marty.
Maurice Thomas Raycroft: Mark, can you touch on the manufacturing strategy and what we're building out for cellular manufacturing?
Thank you. Our next question comes from Geoff Meacham with of Bank of America. Your question. Please.
Marc: Yeah, so we believe that our manufacturing capability can provide a competitive advantage. You know, so we're building the balance and necessary capacity to achieve our in-house manufacturing, as well as securing access through our partnerships with contract manufacturers. We're investing in manufacturing processes and analytics and, you know, beginning to lay the foundation for developing a strong supply chain. Well, thanks for all the perspective, and I'll hop back into queue. Thanks, Maureen.
Asking on for Jeff. Thanks for taking my questions. Just a couple of quick ones from us maybe a little bit more on a high level, but.
For the first on the T. Reg technology, maybe you could talk about.
And what the steps are from from moving from <unk> and <unk>.
All of this approach to getting into the more allogeneic side.
What are what are some of the gating factor of the steps, we need to do to get to.
And to Allergan and then.
I would love to just get your thoughts on on some of the non AAV based delivery mechanisms that have been studied.
For for gene therapy, and hemophilia a.
Thank you.
So Jason and we spent a large part of yesterday talking about a total of this versus allogeneic.
Jeff Mitchum: Thank you. Our next question comes from Jeff Mitchum with Bank of America. Your question, please.
Jeff Mitchum: Thanks for taking our questions, just a couple of quick ones from us, maybe a little bit more on a high level, but first on the Treg technology, maybe you could talk about what the steps are from moving from an autologous approach to getting into the more allogeneic side. What are some of the getting factors, steps you need to do to get into... And then I would love to just get your thoughts on some of the non-AAV-based delivery mechanisms that have been studied for gene therapy in hemophilia. Thank you.
It's a cash.
And gauge science, yes.
Yes, Thanks Benny.
Yeah. So.
The differences between the autologous and allogeneic.
Our.
Our many and.
And there are two two main aspects of it of one is the.
The engineering and the biology that needs to be done.
From from autologous.
Two and allogeneic product, which by.
By definition is the.
The donors sell and bill.
On the patient and the need to avoid.
Lloyd rejection of the cells. So there's there's a lot of complex engineering involved there sell engineering moving on.
Alexander D. Macrae: So Jason, we spent a large part of yesterday talking about autologous versus allogeneic transplantation. It's cutting-edge science, yes?
The single platform.
Jason D. Fontenot: Yeah, thanks, Andy. Yeah, so the differences between autologous and allogeneic are, are many, you know, and there are two, two main aspects of it. One is the engineering and the biology that needs to be done to move from an autologous product to an allogeneic product, which, you know, by definition is, healthy donor cells in, in, a patient, and we need to avoid rejection of those cells.
And it requires that we understand how that engineering to make this the cells more of mean silent.
And is affecting their biology, and making sure that we still have a potent.
And effective product and then on.
On top of that once once you have the strategy for engineering and the cells. You also have to then bring that more complex.
Engineering strategy to the scale, which will allow delivery and the medicine to patients. So both of those areas and places where we're investing.
Jason D. Fontenot: So there's a lot of complex engineering involved there, cell engineering using our Zynclinger platform, and it requires that we understand how that engineering to make the cells more immune silent is affecting their biology and making sure that we still have a potent and effective product. And then on, on, on, on top of that, once you have the strategy for engineering cells, you also have to bring that more complex engineering strategy to scale, which can allow, you know, delivering the medicine to patients. So both, both of those areas are places where we're investing a lot of effort. Yeah, those are the key places.
A lot of effort.
Yes.
As of the key the key places.
And the.
The importance of Allogeneic T. Regs is allows us to move into.
And.
The larger population diseases.
Such as multiple sclerosis, inflammatory bowel disease, even rheumatoid arthritis, where.
The patients treatment more urgently and don't see the price point for normal treatment is different to that in oncology.
Second question most of the other treatment with the other delivery modalities and deliveries really important to us.
We are based on the easy at the moment.
We're constantly scanning the horizon to find other ways to deliver lnp's look encouraging as complicated area. It's a complicated pension status of complicated and.
Jason D. Fontenot: And the importance of allogeneic for Tregs is that it allows us to move into. We are based on AAV at the moment but are constantly scanning the horizon to find other ways to deliver. LNPs look encouraging, it's a complicated area, it's a complicated patent state, it's a complicated interconnection of companies, but we're always on the lookout to find other ways to deliver, particularly beyond delivery but also Non-AAP Ways and Deliver.
Interconnection of of companies who were on.
Luis on the look out just trying to of the lease to deliver particularly beyond the liver but of soon.
<unk> lease and to deliver.
Okay I appreciate the color.
Thank you. Our next question comes on the call Jeremy now with true and your question. Please.
Hi, everyone. Thanks for taking our questions. This is Nick <unk> on for Nicole.
Jeff Mitchum: Thanks guys, I appreciate it.
A quick question I guess with the resurfacing of I could can I concerns from competitors and sickle cell can you share your thoughts or any updated discussions.
The Bulletproof Executive: The Bulletproof Executive, 2013
Operator: So, thank you. Our next question comes from Nicole Germino with Truist. Your question, please.
And what bumps Sanofi on the rest of the open hiseq.
Contributes the oncogenesis and check the source the face to the conditioning debt can you share your thoughts going forward with.
Nicole Germino: Hi, everyone. Thanks for taking our questions. This is Min Bong on behalf of Nicole. Just a quick question.
The program on using reduced intensity conditioning as an option or is.
Alexander D. Macrae: I guess with the resurfacing of oncogenic concerns from competitors in sickle cells, can you share your thoughts or any updated discussions you have had with Sanofi on the risk of buprenorphine as it contributes to oncogenesis? And should the source be traced to the conditioning step? Can you share your thoughts going forward with the program on using reduced intensity conditioning as an option? Or are there any other changes to the trial design that you may want to consider? Thank you.
Is there any other changes to the trial design that you may want to consider thank you.
And thanks for your question and it's very difficult to comment on the.
Safety data coming from our friends of Bluebird.
We know several people there and we knew the or the.
And the kind of company that does the right thing we knew that there'll be making sure that they are understanding the patient journey.
Yes.
We're also confident that we have not seen anything similar with our medicine and <unk>.
Alexander D. Macrae: Thanks for your question, and it's very difficult to comment on the safety data coming out from our friends at Bluebird. We know several people there, we know they are the kind of company that does the right thing, and we know that they'll be making sure that they understand the patient journey. We're also confident that we have not seen anything similar with our medicine and are doing our very best to understand what it is that's appropriate for our patients.
Doing the very best to understand what it is appropriate for patients.
We and Sanofi of a great relationship and.
And we'll be watching and listening and learning from the discussion that goes on the boat will happen with Bluebird, but we feel confident that we are doing something quite different.
You asked another question of the conditioning regimes and.
And once all of those were COVID-19.
Alexander D. Macrae: We and Sanofi have a great relationship, and we'll be watching, listening, and learning from the discussion that goes on about what happened with Bluebird, but we feel confident that we're doing something quite different. You asked another question about conditioning regimes, and once all of us work out a path to efficacy, I am sure that we will try and understand how to optimize conditioning regimes. I'm sure the technologies we're using now are the first generation, and we'll continue to learn about what the best thing to do is.
The efficacy I am sure that we will try and understand how to.
Optimize conditioning rate regimes I'm sure. The technologies, we're using the are the first generation and we'll continue to learn of the best thing to do this.
Great. Thank you so much.
Thank you.
Our next question comes from Gena Wang with Barclays. Your question. Please.
Thank you for taking my questions on two sets of questions. Firstly regarding Fabry program I'm. Just wondering do you have the freedom to choose.
Nicole Germino: Great! Thank you so much.
Choose the dose.
Huidong Wang: Thank you. Our next question comes from Gina Wang with Barclays. Your question, please.
On the day that you see so far from cohort one to cohort two cohort three.
Huidong Wang: Thank you for taking my questions. I have two sets of questions. The first is regarding the February program.
Based on the data.
And <unk>.
I'll start and dose when you dose and the second question is how often do you measure all forgotten and the substrate and as well as the AED two six and factor Shannon.
Huidong Wang: Just wondering, do you have the freedom to choose the dose based on the data you've seen so far, say from cohort 1 to cohort 2 to cohort 3, based on the data, you know, can you choose a certain dose when you dose up? And second question is, how often do you measure alpha-GaA in a substrate and as well as AB2-6 vector shedding? And my second set of questions is regarding the TX200.
And my second set of question is regarding the TX 200 and.
And just wondering Amy.
The improvement.
And the TX 200 of as it comes true since the completion of your T X.
<unk> acquisition and also for the second half this year.
And what would be the initial data from <unk>.
We'll be collecting for the kidney transplant.
Huidong Wang: Just wondering, any additional improvement regarding the TX200 as a count stress since the completion of your TX cell acquisition? And also, for the second half of this year, what will be the initial data sets you will be collecting for the kidney transplant?
Oh, Thank you Gina.
All of a lot of questions. There. So why don't we start with the first part of our own factory with Bettina.
And then we'll come back to it.
The TX 202 so.
Yeah. Thank you Sandy and thank you Jim for the question. So for now what we have disclosed on our dosing strategy for the three cohorts that were looking at the low and the medium and the high dose on.
Alexander D. Macrae: Thank you, Gina. There are a lot of questions there, so why don't we start with the first part around Fabry with Bettina, and then we'll come back to TX200 and TXL.
And that's how we are looking at Idaho the destination.
As of now we are as you point out collecting alpha Gal, a and substrate.
Bettina M. Cockroft: Thank you, Sandy. And thank you, Jean, for the question.
Levels throughout the study and we're doing that at regular frequency.
And those are.
Bettina M. Cockroft: So for now, what we have disclosed about our dosing strategy for the pre-cohort is that we're looking at a low, a medium, and a high dose. And that's how we are looking at our dose escalation. As of now, we are, as you point out, collecting alpha-GalA and substrate levels throughout the study, and we're doing that at regular frequencies. And those are data that we expect to be sharing towards the end of 2021. As I mentioned earlier, we are going to be waiting for those
Data that we expect to be sharing towards the end of 'twenty 'twenty, one and I mentioned earlier, we are going to be waiting for the.
<unk>.
And to share that data.
And as Gino mentioned.
And with shedding.
That's right viral shedding and as well so we're also collecting viral shedding.
And we.
We look forward to sharing that data with you as well at the appropriate time.
So as of June.
Sorry, Yeah, sorry, the question Mike.
Yes, and just wanted to.
You mentioned that you know at the high.
Hi, low dose, but is that fixed dose do you have the freedom to adjust the dose accordingly, and then regarding the collecting the ballpark of data and also the shutting that the extra very interesting senior we'll collect from kind of bolt on biopsy, so off of golf E and the substrate.
Huidong Wang: and Gina Mench.
Huidong Wang: That's right, viral shedding as well. So we're also collecting viral shedding data, and we look forward to sharing that data with you as well at the appropriate time. [inaudible] Sorry, yeah, so just wanted to, you know, like you mentioned that the mid, high, low dose, but is that a fixed dose? Do you have the freedom to adjust the dose accordingly? And then regarding collecting the biomarker data and also vector shutting, that's actually very interesting. I assume you will collect some kind of biopsy.
How often do you collect is that are we talking about weekly or biweekly.
And once every two weeks on monthly if you can give a little more color in terms of the frequency and also of vector of shutting also of what <unk>.
And how frequently would be debt collecting the data.
And so you always have so Steve two questions.
So.
We are the.
And the protocol of Loews flexibility and discussion with the <unk>.
Safety monitoring committee of the dose that we choose from we escalate we have not and will not reveal how often we measure of alpha go on.
Huidong Wang: So for alpha-gal A and a substrate, just how often do you collect? Is that, are we talking about weekly or biweekly? Sorry, once every two weeks or monthly? If you can give a little bit more color in terms of frequency and also vector shutting, also at what point will we do the collecting of the data.
Baidu shaping we were going to put together a package homes. All three cohorts have been dose. So as we can share to use with you something that would be comprehensive and give you a chance to truly understand the effect of our medicine.
Alexander D. Macrae: Gina, you always ask such detailed questions. We, uh... The protocol allows flexibility and discretion with the Safety Monitor Committee on the dose that we choose when we escalate. We have not, and will not, reveal how often we measure alpha-gal and vargo shedding.
Okay.
And then you asked the second question of boat TX. So we phoned from we acquired <unk> the vehicle on a really good process we have.
Alexander D. Macrae: We are going to put together a package once all three cohorts have been dosed so that we can share with you something that would be comprehensive and give you a chance to fully understand the effect of our medicine. And then you asked me a second question about TXL. We found, when we acquired TXL, that they had a really good process. We continue to work on it and understand Tregs, but there's nothing fundamental that we haven't done since the acquisition. And that was why we acquired them, because we believed in them and believed they were good at developing Tregs.
We continue to work on it and.
Understand T regs, but theres nothing fundamental that we have done since the acquisition and that was one of the acquired the because we believe and we believe they were good debt.
Developing T Rex.
Okay.
So if I recall 2018, the Ashley was planning to enter clinical Inc. 2019, with the TX 200, and just wondering what piece of additional time and on any additional prep or.
It seems comes from hasn't changed.
And what additional steps of tea.
In order to move to the clinic and also once you enter the clinic.
What kind of data if you can share a little bit more color on what type of data and you'll be collecting and sharing with us.
Huidong Wang: Okay, so if I recall, in 2018, they actually were planning to enter clinical in 2019 with their existing TX200. Just wondering, what takes additional time, you know, any additional prep, or it seems construct hasn't changed, or what, you know, what additional steps you take in order to move to the clinic? And also, once you enter clinic, what kind of data, could you share a little bit more color on what type of data you'll be collecting and sharing with us?
I don't think we ever expected to be in the clinic and 2019 guidance I think the was a pool could we get into 'twenty and 'twenty.
On the tech transfer process.
And the time of Covid, just takes a little longer we are no we feel and a good police and looking forward to getting into the clinic on.
And dosing of patients lead to this year.
When we.
Alexander D. Macrae: When we, the first patients that we share the data, we will be sharing as much as we can of the biochemistry and biomarkers around their renal function. Our ultimate hope is that the patients are able to reduce their immunosuppression, but that data will clearly be later. But the program is moving ahead. I'm very pleased with its progress, and I look forward to sharing more data with you on that next year.
The first patients that we share the data we will be sharing as much of the count of the biochemistry and Biomarkers on Roe.
And their renal function.
And our ultimate purpose of the patients are able to reduce their <unk>.
And the suppression, but that data will clearly be later, but the programs moving ahead and very pleased with its progress and I look forward to sharing more detail with you on the next year.
Great. Thank you very much.
Huidong Wang: Great, thank you very much.
Yanan Zhu: Thanks, Gina.
Thanks Shannon.
Thank you our net.
Yanan Zhu: Thank you. Our next question is from Yanan Zhu with Wells Fargo Securities. Your question, please.
Next question is from Jonathan Zone with Wells Fargo Securities. Your question. Please.
Yanan Zhu: Great. Thanks for taking my questions and congrats on the progress. So first, a few questions, maybe just a couple questions on the Fabry disease program. I think you said the second dose cohort treated the first patient. How many patients are to be treated in the second dose cohort? And how many patients in total are in the dose escalation cohorts? And by year-end, when you present data, will we see all patients from these dose escalating cohorts, and is there any chance to see the dose expansion cohort as well at year-end? Thank you.
Great. Thanks for taking my questions and congrats on the progress so first of a few questions.
Just a couple of questions on the Fabry disease program.
I think you said the second dose cohort hesitant created and the first patient how many patients are to be treated in the second dose cohort and how many patients in total are in the dose escalation cohorts and by year and when you present the data when we see them all patients from the.
And with SK and escalating cohorts and.
Any chance to see.
Dose expansion cohort as well as at the yearend. Thank you.
The Tina.
Yes of course the.
Operator: [inaudible]
Bettina M. Cockroft: Yes, of course. The first cohort had two patients. And as far as Cohort 2 and Cohort 3 are concerned, we are expecting to dose at least two patients per cohort. We will need two patients dosed in Cohort 2 to then move on to Cohort 3 once we've accumulated sufficient data from those first two patients. We do have the objective of recruiting up to four patients in Cohort 2, and we will also have the possibility of going beyond two patients in Cohort 3.
The first cohort had two patients.
And as far as cohort two and cohort three are concerned we are expecting to does that lead to pace.
We will need to patients dosed in cohort two so then move on to cohort three once we've accumulated.
The data from the price to patients we do have the objective of recruiting.
Two four patients in cohort two.
And we will also have the post.
Possibility.
Moving beyond two patients in cohort three obviously as you can imagine the commitment to presenting data at the end of the year.
Bettina M. Cockroft: Obviously, as you can imagine, the commitment to presenting data at the end of the year will also be COVID-dependent, but we are confident that, as things are looking right now, data from the three cohorts after the escalation at the end of the year, how many patients that will really be COVID dependent and whether we will have patients from the expansion cohort enrolled by that time as well. We will see.
We'll be also COVID-19 dependent, but we are confident to be able to share.
Things are looking right now.
Data from the.
Three cohort.
After the dose escalation.
And at the end of the year, how many patients that will be will really be COVID-19 dependent on whether we will have.
The patients from the expansion cohorts enrolled by the time as well.
We will see.
Yanan Zhu: Got it. That's great.
Got it that's great and then on a.
Yanan Zhu: And then a few questions on TX200. Great to see the program is progressing closer and closer to the clinic. Just curious about the manufacturing process. How do you purify Tregs? Is it through surface markers? And with that process, what kind of purity can be achieved?
A few questions on TX 200, and great to see the program is progressing closer and closer to the clinic.
Just curious about the manufacturing process and how.
How do you purify T regs.
It is true surface markers and with that process, what kind of purity.
And can be achieved and what level of.
Alexander D. Macrae: And what level of contamination with effector T cells could be tolerated? And lastly, perhaps you can talk about, you know, how comfortable you are with your potency assay since this is kind of a first-of-its-kind T cell therapy. Are you comfortable with the way you measure Treg function that could be seen as okay by the regulators? Thank you.
Contamination with the effector T cells.
Could be tolerated and.
And lastly, perhaps if you can talk about how comfortable are you with your potency assay.
And so this is the kind of a first of its kind of.
The cell therapy and are you comfortable with the the way you measure.
The function that could be.
The C. N is okay by the regulators. Thank you.
Jason D. Fontenot: Important questions, and that's the secret sauce that we acquired when we acquired TXL, their understanding of how to purify Tregs. Jason, is there anything you can say about knowing the purity of a Treg?
Important questions on that.
The secret sauce that we acquired when we acquired <unk>.
Our understanding and hoped.
Purify two rigs and Jason is there anything you can share but the.
And then.
Knowing the purity of for Iraq.
Yes, we I mean this is the critical a critical part of the process is obtaining.
Jason D. Fontenot: Yes, we, I mean, this is a critical part of the process, obtaining a very pure population of regulatory T cells as we go into the engineering and expansion of the cells. And so we're very confident about the process that we've developed. We achieve extremely high purities. And in terms of the assays that we use, we have a wide variety of assays that are kind of the benchmark standards in the field for measuring regulatory cell function, both in vitro assays, in a dish, in cell culture, and in animal models. And we're using all of those assays to interrogate the function of our cells, and, you know, obviously, we're very happy with what we're seeing, and that's why we're so excited to be moving this forward.
A very.
Pure population of regulatory T cells as as we go into the the.
Engineering and the expansion of the cells and so where we're very confident on.
About the process that we've developed we achieve extremely high purity and.
And in terms of the.
Of the assays that we use.
We have a <unk>.
Wide variety of assays that are kind of of the benchmark standard.
The standards and the field for measuring regulatory T cell function, both in vitro assays and of dish.
And cell culture and in animal models.
And we're using all of those assays to interrogate the function of ourselves on.
Obviously, we're very happy with what we're seeing and that's why we're so excited to be moving this forward into the clinic.
Yanan Zhu: Got it. Very helpful. Thank you.
Got it very helpful. Thank you.
Thank you. Our next question comes from Eric Joseph from Jpmorgan. Your question. Please.
Eric Joseph: Thank you. Our next question comes from Eric Joseph with JP Morgan. Your question, please.
Hannah: Hi, good afternoon. This is Hannah on behalf of Eric.
Hi, good afternoon, and thank you Hannah on for Eric Thanks for taking our questions just a couple from us.
Hannah: Thanks for taking our questions. Just a couple from us. First, regarding Fabre, with recent data from lentiviral mediated approaches showing pretty compelling efficacy in FabRAVE patients, they have been accompanied by some notable side effects, like potential safety concerns. So with that set up, would you anticipate that AAV therapies might have a lower bar to meet as it relates to efficacy? And then also, in that vein, what dynamic do you think we might expect in a market with both an AAV gene therapy and a lentiviral gene therapy for FabRAVE? Is there anything, in your view, that would prevent a patient who's received lentiviral therapy from going on to be treated with AAV in a commercial setting?
Regarding sabra.
And with the.
And the recent data from London of viral media mediated approach of showing pretty compelling efficacy and fabry patients.
They have been accompanied by some notable like potential safety concerns and so with that setup, but do you anticipate that.
And he was my top of lower by the as it relates to the efficacy and then also in that vein.
And I think we might have stacked and the market with the person.
And the therapy and on to Biogen therapy for Fabry is there anything in your view of that would prevent that from <unk>.
And you don't want the viral therapy from going on that we've seen and with AAV and commercial bank.
Sure.
Marc: and I have another one.
And then I have another one after that.
Hannah: and then I have another one after that.
Okay and thank you is just it's easier to do the one time Mark that's the it seems like you are.
Operator: Thank you. It's just it's easier to do them one at a time. Mark, this seems like you're...
And here.
So I had some difficulty hearing your question, but I think the.
Marc: So I had some difficulty hearing your questions, but I think we can... So the question is, what are the pros and cons of...
The question. The question is the pros and cons of.
The average cell therapy with <unk>.
Marc: For Fabry versus AAV, and could you please ask, is there a place for both of them in the market?
And for Fabry versus ADP.
And could you is there of police for both of them in the market.
Marc: Yeah, so we think that, you know, obviously, a liver-directed gene therapy delivered as a one-time IV infusion and doesn't require any preconditioning regimens would be a better option than patients having to do the preconditioning and go through leukophoresis and other things like that. We also believe that in terms of where the patients are getting their treatments, there is a rationale to make sure that you can have a broad kind of distribution of the agent in the market.
Yes, so we think debt.
Obviously and liver directed gene therapy delivered is at one time, IV infusion and doesn't require any pre conditioning regimens would be a.
The better.
Option then.
And patients having two two.
And do the pre conditioning and go through debt.
So the completions and other things like that.
We also believe debt in terms of where the patients are getting their treatments. There is a rationale to make sure that you can have a broad kind of distribution of the agent.
And to the market.
Marc: You know, I'm not an expert in terms of whether or not someone that would have the cell therapy would be a candidate, but obviously, one of the things that would be important is whether they exhibit neutralizing antibodies that would make them a non-candidate for the therapy. So I think we need more evidence in the clinic to see what would happen in terms of patients post the agrobio cell therapeutic and whether they would be candidates.
I'm not the expert in terms of of whether or not someone debt would have the cell therapy would be of candidate, but obviously one of the things that would be important.
Whether they exhibit neutralizing antibodies that would make them of non candidate for four of the therapy. So I think we need.
More evidenced in the clinic to see what would happen in terms of patients post the.
The average <unk> cell therapeutics and <unk>.
Whether they would be candidates.
Marc: We won't have that answer, obviously, through the initial phases of our ongoing clinical trial work, so it'll be something that will need to be done once they've reached the market. Okay, thank you. That's helpful. And thinking about the zinc finger technology, just wondering how we should be thinking about clinical strategy here in terms of advancement across CNS and mutations, and then specifically for 501, SC501.
And we won't have that answer obviously through the and Nicole.
On phases of our ongoing clinical trial work, so it'll be something that will need to be done once they've reached the market.
Okay. Thank you that's helpful and thinking about the zinc finger technology, just wondering how we should be thinking about.
The clinical strategy here in terms of advancement of coffee and SMA patients and then specifically for 501 five of them.
On line.
And do you have any idea of.
Wow.
Hannah: Do you have any idea why?
And then.
From a clinically meaningful benefit.
Operator: I'm sorry, we lost the latter part of your question. Can you just repeat it again, please?
I'm sorry, we lost the latter part of your question can you just repeat that again please.
Hannah: For ST501, I was wondering if you have any sense of what level of tau protein or mRNA reduction would be clinically meaningful in humans.
For S. T. Five of one just wondering if you have any sense of what level of tau protein or mrna reduction would be clinically meaningful and humans.
Alexander D. Macrae: So that's with our friends at Biogen, so they will lead that conversation, and that's why we partnered with Biogen because they're the experts in Alzheimer's and understand the biology much more than we do. So we are delighted with the capability of the ZincFinger platform, and now it's a matter of matching the technology with the right indication. The ZincFinger itself takes you to a zip code in the genome, and then through a series of attachments, whether it is nucleases, transcription enhancers, transcription repressors, base editors, there's a whole range of things that we can attach to it, allows us to offer a unique set of capabilities that would require a collection of CRISPR companies to do.
And so that's with our friendship Biogen so they will lead the conversation and and that's why we partnered with Biogen pursuit of the experts and Alzheimer's and.
Understand the biology much more than than we do so we are delighted with the capability of the zinc finger platform.
Notice of much of matching the technology with the right indication.
The zinc finger itself takes you to ZIP code and the genome and then through a series of attachments, where there is.
New pleases transcription and homes of subscription refreshes.
Based on editors and there's a whole range of things we can attach to the allows those too.
Offer a unique set of capabilities the would.
And would require a collection of CRISPR companies to do.
Hannah: Okay, that's helpful. Thanks for taking the time to ask the question.
Okay. That's helpful. Thanks for taking the question.
Ritu Baral: Thank you. Our next question comes from Ritu Baral on Cowen. Your question, please.
Yes.
Thank you. Our next question comes from nature of a route with Cowen Your question. Please.
Ritu Baral: Hi guys, thanks for taking the question. Back on your Fabry study, remind me again what the gating protocols are for dose escalation and dose treatment. I believe there was a certain amount of follow-up that you needed for each patient before you could dose up. I'm wondering when that gating might end, such that enrollment and treatment could increase as far as its pace. And then I'm wondering, do you have a pool of screened patients or prescreened patients that you could quickly treat in order to get to a critical mass of data such that you could pick an expansion dose by the end of the year?
Hi, guys. Thanks for taking the question.
Back on the Fabry study or.
And again, what the gating protocols are per dose escalation and the statement I believe there was a certain amount of follow up.
And but you needed for each patient before you could gross up I'm wondering when that date and Mike and.
Such that enrollment.
And and treatment could.
The increase as far as its pace.
And then I'm wondering do you have a.
Cool.
Screened patients or pre.
Prescreen patients.
Quickly treat in order to get to the critical mass with data such that you could pick and expansion dose by the end of the year.
Alexander D. Macrae: Catriona, do you want to try that? And maybe Rob, you could comment afterwards about the plans we have.
Continuing on to Australia, and let the road, where you could comment afterwards about the.
The the plans we have.
Catriona: Yes, so in terms of the amount of data we've mentioned before, we have an SMC in place, the Safety Monitoring Committee, that will look at the data and we need two weeks of data from two patients to assess the data and move to the next cohort. And yes, we do have patients prescreened and lined up. So that's why earlier on I was mentioning that we feel pretty confident, obviously, COVID permitting, to be able to reach the stage at the end of the year to be sharing data from our escalation cohort.
Yes so.
In terms of the amount of data I think.
You mentioned the floor, we have and I can see.
The in place the safety monitoring committee that wasn't the data and we need two weeks of.
The data.
From two patients.
To move to.
First of the data and move to the next couple of board and yes, we do have patients screened and.
Hi, Scott.
So that's why you're on and I was mentioning that.
We feel pretty confident there'll be C code, the permitting to be able to reach the stage at the end of the year to be sharing data from our escalation cohort.
Yeah.
Okay.
Rob: Rob here, now less than four weeks into my journey with Sangamo, so I'll keep my comments at a higher level. Um, we'll move as fast as we can as the data allows. We're completely data-driven and, uh, seal the urgency about getting treatments to patients as quickly as we can as the data allow us to do that. We're looking at this very carefully and look forward to sharing what we've learned at the end of the year.
Rob here.
Now.
Less than four weeks into my journey with Sangamo.
Comments at the higher level.
We'll move the SaaS as we can as the data were.
Completely the hit Robyn.
And.
And on.
So the urgency about getting true.
Treatments to patients.
And.
As quickly as we can as the data allow us to do that.
We're on.
We are.
Looking at this very carefully and look forward to sharing what we have learned at the end of the year.
And we're planning for success, we're planning for.
Alexander D. Macrae: And we're planning for success. We're planning for... Expansion Cohort, Space Threes, that is one of the main focuses of the company to ensure that we're ready when this medicine hopefully works to drive forward into phase three and, as Rob says, get us into patients.
The expansion cohorts phase threes that is.
One of the main.
<unk>.
The focus is of the of the company to ensure that we are ready for and this medicine and hopefully works to drive forward into phase III and as Rob says gets us into patients.
Ritu Baral: Two quick follow-ups to that. One, what treatment duration do you think that you'll have across the cohorts when you pick your expansion dose? And two, when you enter the expansion dose, are you going to be in a good enough CMC-wise condition to say that that is your final commercial product? So when do we treat
Two quick follow ups to that.
One what treatment duration.
And we'll have across the cohort.
When you pick your expansion dose and two.
When you enter the expansion goes are you going to be and a good shape the M y.
That is your final commercial product.
Ritu Baral: So when did we treat the first patient, Patrina? Petrina, we can't hear you. Apologies.
So when did we treated the first patient bettina.
But you know we can't hear you.
I think the unused at the apology.
Yes.
Catriona: We treated the first patient in Cohort 1 around Q3 last year, and so we will have a year's worth of follow-up by the time we report out towards the end of this year for the first cohort.
And we did treat the first patient.
In cohort one.
And Q3 last year on.
And so we will have a use for that.
Follow up.
By the time, we reported out towards the end of the Q4 for the first cohort.
Alexander D. Macrae: and as regards the manufacturing processes, we're continually working to improve them. That's what one does in this field, and we do not see this as something that is preventing us from moving into phase three and beyond.
And as regards the manufacturing processes, we're continually working to improve its one dose and the skills and.
We do not see this as something that is getting moving into phase III and beyond.
Ritu Baral: Great. Thanks for taking all the questions.
Great. Thanks for taking all the questions.
Benjamin Jay Burnett: Thank you.
Thank you.
Benjamin Jay Burnett: Thank you. Our next question comes from Ben Burnett with Cecil. Your question, please.
Thank you. Our next question comes from Ben Burnett with.
And so your question please.
Benjamin Jay Burnett: Hi, thank you very much. I wanted to ask another question about the TX200 program. I guess, how do you think about dosing in the TX200 program, and do you expect CAR Treg cells to expand? And really just trying to get at, like, what's the expectation for efficacy in the low-dose cohorts in the solid organ transplant study? Thank you.
Alright. Thank you very much I wanted to ask also another question about the TX 200 program.
I guess, how do you think about dosing and the TX two and our program and do you expect car T. Reg cells to expand it really just trying to get out like what's the expectation for efficacy and the low dose cohorts.
In the solid organ transplant study thank you.
Jason D. Fontenot: So we never guide to, you know, the first dose of any study is always a balance between prudence and hoping that that patient will get some benefit, but until you do the study, you don't know. Jason, Treg expansion, or what happens to Treg when it's given?
So we never guide to.
The first stores of any study is always the balance between prudence and hoping that the piece of that patient and we'll get some benefit but until you do the stuff that you don't know.
Jason T Reg expansion or what happens to the two <unk> Griffin.
Jason D. Fontenot: Yes, thanks, Andy. We definitely expect the Tregs to expand in the patient upon encountering the cognate ligand for the CAR receptor that we're engineering the Tregs with. So we certainly anticipate, and that's by design, that when the Tregs get to the tissue where the antigen is expressed, they will be activated through their CAR receptor, and that will trigger them to proliferate and acquire their kind of immunoregulatory and suppressive properties.
Yes, thanks Sandy.
We definitely expect the the T regs to expand.
And the patient pull on upon and Telenor with the.
And the cognate ligand for the for the car receptor that and your engineering the T regs with.
So, we certainly anticipate and thats by design that.
And the T regs and get to and tissue where the.
Of the antigen is expressed they will will be activated through their car receptor and.
That will trigger them to proliferate and to acquire their kind of.
Immuno regulatory and EMEA.
Suppressive properties.
Jason D. Fontenot: So that's what we expect to see, and that's what we've seen in the preclinical data that we've shown, and the preclinical data that our partner, Megan Leving, our academic partner, has published. So we definitely expect expansion.
So.
That's what we expect to see and that's what we've seen and the preclinical data.
We've shown and the preclinical.
Data that are part of Europe.
Maybe and loving our academic partner made and lending to the public.
So we definitely expect the expansion.
And if I may add something too.
Bettina M. Cockroft: And if I may add something to what Jason has Summarize. In terms of initiating the study this year, we do intend to initiate the study, but similar to other genetically engineered cell therapy approaches, patients will undergo a leukophoresis procedure from which their Treg cells will be isolated and engineered and prior preserved, and the HLA-A2 negative patient will subsequently undergo transplantation surgery and then following a recovery period will receive their personalized TX200 drug candidate and so as a result of this detailed process we expect that dosing of patients will occur several months after their enrollment and as such dosing may maybe this year or next year we're not committing to this year but certainly to initiating the clinical trial this year.
So what Jason.
Summarized.
In terms of initiating the study of the yeah, we do intend to initiate the study similar to the other genetically engineered cell therapy approaches patients will undergo and leukapheresis procedure from which the T. Reg cells will be isolated and Geneva and private.
And the HLA, a two negative patients subsequently undergo transplant patient surgery.
And then following the recovery period will receive the price of a nice TX 200 drug candidate and so as the results of the detailed posted and we expect the dosing of patients will it.
Several months off the bat relevant and.
And as such dosing me, maybe the zero next year, we're not committing to the only thing with tier debt suddenly to initiating the clinical trial.
Benjamin Jay Burnett: Okay, okay. Very helpful. And then I also just wanted to see if, and apologies if I missed it, but if you could provide any additional color on the timeline for selecting candidates under the Novartis collaboration.
Okay. Okay.
Very helpful and.
And then I also just wanted to see if if and apologies if I missed it but if you could provide any additional color on the timeline for selecting candidates under the Novartis collaboration.
It's on.
Alexander D. Macrae: It's... We know their targets. They made the choice to, instead of coming up with a laundry list of ten potential targets, that they would decide on three, and they shared them with us. So we know their targets and are working closely with them.
We know their targets.
The the.
The made the choice to instead of coming up with.
A laundry list of 10 potential targets.
They would decide on <unk> III and the shared them with us So we know their targets on her.
Working closely with them.
Benjamin Jay Burnett: Okay, but I should have asked that differently. In terms of disclosing those targets, is there any expectation there?
Okay, but.
And I should've asked that differently in terms of disclosing the is hard to say the expectation there.
Alexander D. Macrae: That's Novartis' choice if they choose to disclose it.
That's the Novartis is choice when they choose to disclose it.
Benjamin Jay Burnett: Got it. Okay. All right. Well, thank you very much.
Got it okay, alright, well, thank you very much.
Thank you.
Thank you.
Andreas Argyrides: Thank you.
Andreas Argyrides: Thank you. Our next question is from Andreas Argyrides with Wedbush Securities. Please go ahead.
Our next question is from and yes, I can leave us with Wedbush Securities. Please go ahead.
Andreas Argyrides: Thank you, and good evening. Thank you for taking our question. This is Andreas on behalf of Eliana Misatos.
Thank you and good evening.
Thank you for taking the question. This is andres on for Alere and restart those.
Andreas Argyrides: Two questions, and I know everyone's asked about Fabry, but just what can we expect from updates throughout the year? How regularly would we be getting them? Would they be milestone-based updates on the selection, etc.? And then, broadly speaking, on partnerships and how you guys are thinking about those. You've done an excellent job in the past, and how are those discussions progressing, and any thoughts on additional invocations, etc.? Thank you.
Two questions and I.
Everyone's asking about fabry, but just.
What can we expect from updates throughout the year, how regularly would we be getting them with the milestone based and updates on dose selection of et cetera, and then just broadly speaking on partnerships and how you guys are thinking about.
Those you've kind of an excellent job.
And in the past and how are those discussions progressing and any thoughts on the additional and vacations et cetera. Thank you.
So it's sort of thank you for your.
Alexander D. Macrae: So, thank you for your questions. We've said that we won't give any more indication of the Fabry trial, either doses or efficacy or the safety profile, until we've dozed off three cohorts. So it'll be the end of the year before we see anything significant. Mark, do you want to talk about partnerships?
On your questions. We've said that we want to give any more indication of the February trial lethal doses or <unk>.
Efficacy or the safety profile until we do so three cohorts. So it's it will be the end of the year before we see anything significant.
Mark do you want to talk about partnerships.
Marc: Sure. Thanks, Andy.
Sure. Thanks, Sandy so.
Marc: So, you know, we've had the opportunity to see multiple collaborations with blue chip pharma companies that we believe reinforce the promise of our science and our platform. Most recently, obviously, with the Biogen and Novartis deals completed in 2020. These collaborations have really important financial and strategic benefits for us. You know, they've provided about $815 million in upfront and milestone payments, and we've got the potential across these partnerships to earn about $7 billion in milestones in addition to royalty payments.
We.
Had the opportunity to.
The multiple collaborations with Blue chip pharma companies that we believe reinforce the promise of our science and our platforms.
Most recently, obviously with the the Biogen and Novartis deals completed in 2020.
These collaborations have really important financial and strategic benefits for us.
And they provided about $815 million and upfront and milestone payments and we've got a potential across these partnerships to earn about $7 billion and milestones. In addition to the royalty payments.
Marc: The way we look at partnerships is where they can bring therapeutic or clinical experience or expertise, I should say, as well as their commercial resources to more rapidly bring these medicines to patients, then we would look at those. And in many ways, the way we look at this is that it's an expansion of our R&D portfolio. So in many cases, they come to us with targets within disease areas that they're experts in and have identified things that our team has not even thought about applying our technologies to.
The way, we look at partnerships of where they can bring a therapeutic or clinical experience and our expertise I should say as well as the commercial resources to more rapidly bring these medicines to patients.
And then we would look at those and in many ways. The way we take a look at this is this and expansion of our R&D portfolio.
So on many cases, they are coming to us with targets and disease areas that they are experts in and.
And have identified things that our team has not even thought about applying our technology to.
Marc: So going forward, you know, we believe that there is an opportunity to create value for the industry and, more importantly, for patients. And so we'll continue to take a look at where we can address markets, leveraging our partners' resources and expertise in those areas. But we really want to underpin that we have a real focus now on creating a portfolio of products which are wholly owned and will allow Sangamo to take these all the way through to patients.
The going forward.
We believe that there is an opportunity to create value for the industry and more importantly to two to patients and so we'll continue to take a look at.
And where we can address markets, leveraging our partners and resources and expertise and those areas but.
But we really want to underpin that we have a real focus now on creating a portfolio of products, which are wholly owned and will allow the sangamo too.
Take these all the way through the patients.
Marc: Okay. I appreciate that. And Sandy, just to clarify, and maybe I also didn't phrase the question correctly, you have provided updates on dosing the different cohorts. But are we to expect no update until data whatsoever on where the program stands, et cetera, until the end of the year so we won't ask any questions on future calls, et cetera?
Okay, I appreciate that and Sandy just to clarify net and I, maybe I also didn't phrase. The question correctly you have provided updates on dosing.
And the different cohorts are we to expect no update until data whatsoever on where the program stands and et.
Et cetera until the end of the year. So we won't ask the questions.
On the future calls et cetera.
Yes.
Andreas Argyrides: So let me try and navigate that one, so at our quarterly calls, we'll tell you the progress of the study, but we won't tell you the results or biochemistry and those kind of things, simply because our experience now is the story is more... understandable if you can see the three cohorts and some period of data. So we want to get this to you as quickly as possible, so I look forward to speaking with you at the end of the year.
And Linda let me try and navigate on one.
True to our quarterly calls we will tell you the progress of the study, but we wouldn't tell you dose of results or biochemistry and those kind of things simply because we have experienced no is the story is more.
Understandable, if you can see the three cohorts and <unk>.
Some periods of two two so we want to get this to you as quickly as possible. So look forward to speaking at the end of the year.
Andreas Argyrides: Okay, much appreciated, and congratulations on all the progress. Looking forward to the update. Thank you.
Okay, much appreciated and congrats on all of the progress looking forward to the outcome. Thank you.
Deputy Chattopadhyay: Thank you. And our last question comes from Deputy Chattopadhyay with Guggenheim Securities. Your question, please.
Thank you and.
And our last question comes from debt to cap the <unk> with Guggenheim Securities. Your question. Please.
Deputy Chattopadhyay: Hi guys, this is Aaron on ForDevJIT. Thanks for taking my questions. So, on the FODRIP program, can you talk about the type of patients that you would expect to enroll in the treatment, such as are they perhaps not responsive to ERT, they have core renal function, or are there other sort of disease symptoms that may push them towards using the gene therapy as opposed to, you know, perhaps remaining on ERTs or going to ERTs? And if you can, comment on...
Hi, guys that this is Aaron on for Deb, Jay Thanks for taking my questions.
So on.
On the five rate.
The program can you talk about the type of patients that you would expect to enrol in in the treatment such as are they perhaps not responsive to the ERP. They of course renal function or the other sort of the symptoms that may push them towards music and the gene therapy as opposed to.
Perhaps remaining on ear of teeth are going to ERP.
And and and we have comedy.
Operator: We haven't given any detail; we haven't given any detail about the type of patient. It's because it's a very...
We haven't go ahead of any detail, we haven't given any details of the type of patient.
Okay.
Because it sort of theory.
Alexander D. Macrae: There are several categories of Fabry patients, and the one you choose for these studies is something that each of the companies is guarding carefully and thinking about, with great input from outside experts.
There are several cats.
Categories of fabrication and the one you choose for the studies is something that each of the companies is guarding carefully and thinking of boat.
And with great input from outside the experts.
Alexander D. Macrae: Okay. And then, if you can comment at all about whether you incorporate any learnings into the steroid regimen being used in the Fabry trial from hemophilia.
Okay.
And then if you can comp.
Comment at all about if you incorporate any learnings into the steroid regimen being and.
The fabry trial from the the hemophilia.
Alexander D. Macrae: So we've learned a lot about liver function tests and the use of steroids in haemophilia, and we have applied that learning to what we do in Fabry, but we haven't said what we're doing in Fabry.
The program.
So we've learned a lot of boat liver function tests and use of steroids from hemophilia and we have applied the learnings to what we do and temporary but we Havent said what were doing in February.
Deputy Chattopadhyay: Okay, oh, looking forward to finding out. All right, thanks, guys.
Okay.
Looking forward to finding out alright, thanks Scott.
Deputy Chattopadhyay: Thank you. Thank you very much.
Thank you very much.
Erin Feingold: Thank you, and this concludes our Q&A session. I would like to turn the call back to Aaron Feingold for his final remarks.
Thank you and this concludes our Q&A session I would like to turn the call back to the iron triangle for the final remarks.
Erin Feingold: Thank you once again for joining us today and for your questions. We look forward to keeping you updated on our future developments. Hope you all have a great day. And with that, ladies and gentlemen.
Thank you once again for joining us today and part of your question. We look forward to keeping you updated on our future development.
I'll have the Dayton, Inc.
And with that ladies and gentlemen, and we thank you for participating in today's program. You may now disconnect have a wonderful night.
Operator: And with that, ladies and gentlemen, we thank you for participating in today's program. You may now disconnect. Have a wonderful night.
[music].
BF-WATCH TV: Copyright 2020. All Rights Reserved.
BF-WATCH TV: BF-WATCH TV 2021
Operator: ???