Orchard Therapeutics PLC (NASDAQ:ORTX) Q4 2018 Results Conference Call March 21, 2019 9:00 AM ET

Company Participants

Renee Leck – Director, Investor Relations

Mark Rothera – President, Chief Executive Officer

Bobby Gaspar – Co-Founder and Chief Scientific Officer

Andrea Spezzi – Co-Founder and Chief Medical Officer

Frank Thomas – Chief Financial Officer

Conference Call Participants

Anupam Rama – JPMorgan

Graig Suvannavejh – Goldman Sachs

David Nierengarten – Wedbush Securities


Good day, ladies and gentlemen, and welcome to the Orchard Therapeutics Fourth Quarter 2018 Earnings Conference Call. At this time all participants are in a listen-only mode. And later we will conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions]

I would now like to hand the call over to Ms. Renee Leck, Director of Investor Relations.

Renee Leck

Thanks, Amanda. Good morning, everyone, and welcome to Orchard’s first earnings call reviewing our recent progress and financial results for 2018. You can access slides for today’s call by going to the investors section of our website orchardtx.com.

Before we get started, I’d like to remind everyone that statements we make on this call will include forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements. As a result of various risk factors uncertainties and other factors, including those set forth in the Risk Factors section of our most recent Form F1 filed with the SEC, and any other filings that we may make with the SEC.

In addition, any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements.

And with that, I’ll turn the call over to President and CEO Mark Rothera.

Mark Rothera

Thank you, Reene. We are relying to spend some time with you this morning to give you an introduction to Orchard, our exciting vision, our significant portfolio of gene therapy product candidates and planned milestones for 2019 and beyond. Since this is, I know you recall [indiscernible], you’ll be hearing from several members of Orchard’s Executive Leadership Team, as we discuss our approach to the development of our gene therapy product candidates, which have shown transformative potential in patients.

Following my introduction and review of our vision and 2019 priorities, Co-Founder and Chief Scientific Officer, Bobby Gaspar, will review our scientific platform and the Primary Immune Deficiencies franchise. Andrea Spezzi, another Co-Founder and Chief Medical Officer will follow with a review of our Neurometabolic Disorders franchise and our transfusion-dependent beta-thalassemia program. Frank Thomas, our Chief Financial Officer, will close with our financial results and review our plans, 2019 milestones.

2018 was a vitally important year for Orchard. We made significant progress expanding and advancing our gene therapy pipeline, and also strengthening our balance sheet with two successfully raises, including an IPO in the fall. We’ve come a long way towards achieving our vision of building a global, fully-integrated pure play gene therapy company dedicated to transforming the lives of patients with rare, life-threatening diseases. I believe our power successes and ability to continue to execute on our vision are grounded in several features that differentiates us from other gene therapy companies.

Firstly, our focused approach. We are a company focused on developing autologous ex-vivo, hematopoietic stem cell gene therapies for rare genetic diseases. Secondly, the breadth and depth of our portfolio as well as the durability of response seen in our clinical data. Our approach of genetically modifying hematopoietic stem cells known as HSCs have enabled us to treat patients in our clinical trials in five different disease areas and across three physiological systems showing transformative potential after a single administration. Furthermore, with over 150 patients treated and follow-up extending up to eight years or more, we believe we have one of the most robust comprehensive clinical data sets in the field of gene therapy.

Finally, our expertise in this rapidly evolving field covered every aspect of the organization we had built industry leading capabilities and recruited world-class leaders in research, medical, corporate strategy, manufacturing, regulatory fares and commercialization. We also have a deep understanding of developing and commercializing medicines to treat rare diseases. I believe we are positioned to lead from the bench to the bed side in this innovative field.

Having said the last 20 years, in the field of rare diseases, I know how hard it is to develop and deliver medicines that have the potential to fundamentally transform patients’ lives. At Orchard, we are doing just that across multiple rare diseases that have limited or no available treatment options through a single administration of our gene therapies. Our pipelines spend three rare disease franchises, Primary Immune Deficiencies, Neurometabolic Disorders and Hemoglobinopathies. Our portfolio includes one commercial product for ADA-SCID called Strimvelis, as well as five clinical stage programs and a robust pipeline of preclinical programs.

Our lead Primary Immune Deficiencies and Neurometabolic Disorders programs target underserved rare disease populations with a combined annual incidence of 1,000 to 2,000 patients in markets around the world where orphan drug treatments are often reimbursed. We estimate a potential market opportunity of at least $2 billion per year based on the infant populations in these diseases. The prevalent populations of some of these conditions and our program in transfusion-dependent beta-thalassemia represent considerable potential upside.

Now I’d like to focus on this year, 2019. We’ve set ourselves an ambitious set of goals, chief among them, to move our three lead programs in ADA-SCID, MLD and WAS to regulatory filings in the U.S. and Europe over the next three years. Each of these programs has already met their primary endpoints of their registrational trials with data presentations planned over the course of this year. We will also define a registrational study for our fourth clinical program in X-CGD, which achieved clinical proof of concept at the end of last year.

Finally, we await Proof of Concept data in our fifth clinical program in transfusion-dependent beta-thalassemia and continued to expand our clinical portfolio with our sixth gene therapy program in MPS-IIIA preparing to enter the clinic. Bobby and Andrea will provide color on these programs. But first, I would like to review some important progress we have made in the area of technical operations.

Technical operations play a pivotal role in the development, manufacture and delivery of the personalized gene therapy medicines we have pioneered. For our first three potential launches, our commercial manufacturing platform is based on the CMO partnership networks we have established with some of the leaders in the field, including Lonza, MolMed and Oxford BioMedica.

Given the importance of building in-house manufacturing capabilities and the breadth of our portfolio, we announced the lease of a facility in Freemont California at the end of last year. The new facility will complement our existing CMO network and will enhance our ability to develop and deliver ex-vivo lentiviral gene therapies for a wide range of diseases on a global scale.

Our strategic investment in Tech Ops extends beyond the facilities to the people we hire and the capabilities that we are building. Earlier this week, we welcomed Ms. Ran Zheng to the executive leadership team as Chief Technical Officer oversee our global manufacturing and technical operations functions. She comes to Orchard with over 20 years of experience in the field, most recently as Vice President of Amgen, overseeing end-to-end supply chain and manufacturing operations to enable global clinical developments, product launch and commercial supply. With global leadership experience and the strong technical skill set, Ran’s appointment aligns with our strategy to commercialize multiple gene therapies and thereby serve patients and families across the world over the coming years. We welcome her to the team.

I’ll now turn over the call to Bobby, our Chief Scientific Officer, to review our technology platform and clinical development in our Primary Immune Deficiencies franchise. Bobby?

Bobby Gaspar

Thanks Mark. As one of the founders and CFO of Orchard, I’m thrilled by the progress we’ve made so far as a company. Before joining Orchard, I spent 25 years as an academic physician with special interest in the treatment of severe Primary Immune Deficiencies, including gene and the cell therapy. Some of the work on our ADA-SCID and X-CGD programs originated from our work at University College London, until now X-CGDs lead programs approaching the first regulation filings is an incredible achievement.

At Orchard, our approach is to treat severe genetic disorders using ex-vivo autologous hematopoietic stem cell gene therapy. These therapies have been designed to treat individuals with monogenic disorders with a single administration of their own HSCs so that be modified to carrier working copy of the faulty or missing gene. The use of hematopoietic stem cells for this purpose is significant for two main reasons. Firstly, their multipotency; and secondly their intrinsic self renewing capacity that produces a durability of fact. HSCs differentiate into a wide variety of cells within the blood stream, including immune cells, granulocytes, red blood cells and platelets. And importantly, a sub population of these cells can also become microglia in the brain. So by correcting this one cell tide, you have the ability to correct a whole series of cells, and therefore correct whole series of different diseases, including the three physiological systems represented by our portfolio. HSCs also have an intrinsic ability to self review, and by leveraging that capacity, our gene therapies have been showing to provide a durable long-term effect following a single administration.

Looking at our data, we can confirm that the engraftment of gene modified HSCs at an early of three to six months of the treatment can give rise to the durability effect, which has been sustained for up to eight years or more in our clinical programs.

I’d also like to talk about the use of lentiviral vectors. For all of our clinical development programs, we are using a lentiviral vector as a tool to introduce a working copy of the gene back into the patients’ own HSCs. We believe that the ability of lentiviral vectors to integrate into the chromosomes of patients’ HSCs has multiple advantages, including stable integration of the modified gene into HSCs, which give rise to the durable expression of the target protein of a single administration of gene therapy. Also the safety profile of lentiviral vectors has now been demonstrated in our clinical studies for some time with the first patients treated over eight years ago. In these studies there has been no demonstration of persistent clonal dominance or proliferation.

Launching a cryopreserved formulation of the gene modified HSCs is another important aspect of our strategy. The trial for our three lead programs for ADA-SCID, MLD and WAS were initiated using a fresh-cell product, but if approved, we like others, plan to commercialize these products using a cryopreserved formulation. By extending the product’s self life, we’re able to focus the process around the patient. We can collect the cells at their local treatment center, ship the cells to a manufacturing facility, genetically modify and cryopreserve the HSCs, and then ship them back to the patients’ local treatment center to be reintroduced into the patient.

We are undertaking regime work for the first three programs to show in vitro CMC comparability between the fresh and cryopreserved formulations by evaluating HSC cell number, viability, sterility and VCN numbers. We will also be looking at data from patients receiving the cryopreserved product at six months to ensure that the cryopreserved cells are performing in the same way as the fresh cells. Our earlier stage product candidates, including those for X-CGD transfusion-dependent beta-thalassemia and MPS-IIIA are already being developed with the cryopreserved product formulations. In total, we’ve treated over 30 patients with a cryopreserved product across our portfolio, and we will be releasing data and ADA-SCID and MLD later this year.

Now that I’ve reviewed our approach, let’s move on to our Primary Immune Deficiencies franchise. ADA-SCID is a rare life-threatening inherited disease of immune system. Patients are born without functional limp size [ph], which leaves them vulnerable to severe and recurrent bacterial viral and fungal infections. The first symptoms of ADA-SCID typically manifest during infancy, and without treatment the condition is almost uniformly fatal within the first two years of life. Bone marrow transplantation is the current standard of care for patients with ADA-SCID and the other immune deficiencies in our portfolio. But this approach carries a significant risk of mobility and mortality, and is dependent on the availability of well-matched donor.

We are developing OTL-101 as an alternative to patients with ADA-SCID. In a registrational trial where 20 patients have been followed for at least two years, we have shown that in comparison to a historical control group receiving transplant, OTL-101 demonstrated a 100% overall survival and a 100% event-free survival both of rates of 88% and 56%, respectively seen with transplants. Treatment with OTL-101 was also well-tolerated and had a positive benefit risk profile. In addition, sustained VCN and ADA enzyme activity was seen in all patients through 24 months supporting the durability of this treatment.

With more than 60 patients treated with OTL-101 and up six years of follow up, data from this program demonstrates that by engrafting autologous gene modified hematopoietic stem cells we can achieve durable recovery of the immune system. Based on our ongoing discussions with the FDA, we expect to file a BLA submission, in this indication, in 2020. This submission will also include supported data derived from 10 patients treated with a cryopreserved formulation, which we plan to present later this year.

Our second program in Primary Immune Deficiencies is OTL-103 for the treatment of boys affected with Wiskott-Aldrich syndrome or WAS. WAS is a life-threatening inherited disease characterized by immunodeficiency, autoimmunity, an abnormal type of function and manifest with current severe infections and severe bleeding episode, which is the leading causes of death in this disease. The median survival without treatment in this condition is 14 years. We have an 8-patient registrational trial ongoing this disease, which has achieved its primary endpoint and the dates from which will be released in full later this year.

Our most recent data set shows a significant reduction in both the frequency and severity of infections and severe bleeding episode from patients before and after treatment with OTL-103. OTL-103 was also well tolerated with some patients approaching eight years of follow up. A trial using a cryopreserved formulation is on track to be initiated later this year, and we plan to submit an MAA with the EMA and a BLA with the FDA for this program in 2021.

Our last program in Primary Immune Deficiencies is X-CGD, an inherited immune deficiency disorder that arises from the inability of patients’ neutrophils to effectively kill bacterial and fungal infections. Patients with X-CGDs are prone to chronic deep-seated severe infections including liver, lung and brain abscesses. Living with the burden of chronic infections makes them poor candidates for transplant with the high risk of mortality. This condition is life-limiting with mortality estimated at approximately 40% by the age of 35 without definitive treatment. We are developing OTL-102 for this indication and recently presented data demonstrating for the first time that HSC gene therapy has the potential to correct the functional aspects of this disease. At 12 months post therapy, six or seven eligible patients treated with OTL-102, showed greater than 10% functional neutrophils, which is a minimum threshold shown clinically protect against severe bacterial and fungal infections. These patients were also no longer receiving CGD-related prophylactic antibiotic treatment as of their last follow-up, and demonstrated stable vector copy number in neutrophils at 12 months, which correlates to the engraftment of long-term repopulating hematopoietic stem cells. We are in the process of designing a registrational trial and intend to seek regulatory input on future clinical development this year.

I will now turn the call over to Andrea, who will start by reviewing our Neurometabolic Diseases franchise. This is an exciting set of program for us because the clinical data demonstrates that ex-vivo HSC gene therapy has the ability to prevent neurological deterioration in the severe neurodegenerative condition. Andrea?

Andrea Spezzi

Thank you, Bobby. As a fellow physician and co-founder of Orchard, I am equally proud of the progress we have made with our clinical development programs to date. Our lead program in the Neurometabolic franchise is MLD, a severe neurodegenerative condition caused by mutations in the ARSA enzyme. MLD is characterized by the rapid deterioration of motor and cognitive function and presents the spectrum of severity ranging from early to late onsets. Late infantile MLD is a most common and most severe form of the disease with a mortality rate of 60% by the age of five. The children affected by this condition will start to lose motor and cognitive function in the first or second year of life and experience seizures, rapid cognitive decline, difficult in talking and swallowing and ultimately progress to vegetative state. Currently there are no treatment options available for MLD, which is why we are developing OTL-200 in this indication. We are very encouraged that in the large proportion of early onset patients affected by this devastating condition, OTL-200 has been drawn to stop or in some cases delay disease progression over a period of up to eight years. The primary endpoint of our registrational trial in 20 late infantile and early juvenile patients was to demonstrate a 10 percentage point increase in average motor function scores versus natural history of 24 months. To illustrate the transformative potential of our program, we saw compelling treatment differences of 65% and 45% in gross motor function scores in the late infantile and early juvenile patients compared to the age match untreated natural history counterparts. And most of them maintained normal condition. Treatment with OTL-200 has also been generally well tolerated with no instances of insertion on mutagenesis with over 8 years of follow up. The three years follow up data has been eclipsed as an oral presentation of the European Society for Blood and Marrow Transplantation Annual Meeting, or EBMT, next week. And we plan to submit an MAA for OTL-200 with the EMA in 2020, followed later by a BLA with FDA.

Given the data we have seen in MLD, we are greatly encouraged by the potential to treat all the neurometabolic diseases that affected brain using ex-vivo gene therapy. We have preclinical work ongoing in a number of these disorders and wanted to highlight two promising programs in MPS-IIIA and MPS-IIIB, where we have achieved preclinical Proof-of-Concepts. MPS-IIIA and MPS-IIIB are life-threatening neurometabolic diseases with no effective treatments or approved therapies.

Within 1 to 2 years after birth, MPS-IIIA and MPS-IIIB patients experienced progressive neurological decline, including a speech delay and eventual loss of language, behavioral disturbances and potentially severe dementia. Ultimately, most patients with MPS-IIIA progress through a vegetative state. Our goal for 2019 is to submission of a clinical trial application for OTL-201 for MPS-IIIA prior to the start of a clinical trial.

Our last clinical stage program is OTL-300 in transfusion-dependent beta-thalassemia, which is the most severe form of beta-thalassemia. These patients require eight or more blood transfusions per year with a number of transfusions correlating to disease severity. In the absence of regular blood transfusions, which carry a competition, this disease is initially phased out infancy. Transfusion-dependent beta-thalassemia is one of the most common genetic diseases with the global incidents estimated as approximately 25,000 symptomatic individuals each year. We are developing OTL-300 in this indication in a clinical Proof-of-Concept trial of nine patients, including six pediatric patients with severe genotypes including [Indiscernible].

Data from this program was featured in the Nature Medicine’s publication in January and demonstrated that OTL-300 reduces or eliminates the need for transfusions in the majority of the patients treated. Among the seven patients with at least 12 months of follow-up, significant reductions in transfusion frequency and volume requirements were observed in five patients and three of the four pediatric patients were transfusion-free one month post-treatment. Once all the nine patients complete 12 months of follow-up, our goal is to report the clinical Proof-of-Concept data for these indications.

As you can see, we have a very active set of clinical development programs here at Orchard and look forward to advancing them on multiple shrunk as the year unfolds.

Before I close, I will like to spend a few minutes on our approach to expedite clinical development targeting very rare conditions with limited or no therapies. We believe our deep pipeline of ex-vivo autologous HSC gene therapies allow us to consolidate our knowledge and learnings across our programs. Being as a full front of development for this type of therapy, we are rapidly gathering compelling clinical results in several diseases areas using innovative approaches and enclosed communications with regulators. One example is the use of an adaptive approach using a single pivotal trial originally designed as a Phase 1/2 trial with a strong clinical meaningful primary endpoint and the use of historical comparative data. For more details, I invite you to review our OTL-101 presentation at ASBMT.

We are also discussing with regulators new creative ways to generate a common set of early data for several programs with similar diseases variance and vector transduction mortalities to support the later stage clinical development. These complex innovative designs will enable more efficient clinical development and rapid patient access in areas of high unmet need. These are evolving discussions.

I will now turn the call over to our CFO, Frank Thomas, to review our financial results and summarize our planned 2019 milestones. Frank?

Frank Thomas

Thank you, Andrea. 2019 is shaping up to be busy year for Orchard. And we are well capitalized to execute our business plan. Let me quickly recap our financial results. Today’s press release included figures for the full year and the second half of 2018. Beginning in 2019, we expect to report quarterly numbers consistent with many of our peers.

Since the GSK transaction in April 2018, we recorded just over $2 million in net product sales from Strimvelis, a first ex-vivo gene therapy product approved by the EMA for the treatment of patients with ADA-SCID. Strimvelis gives us a great opportunity to begin to build out our commercial and medical footprint in advance of our upcoming filings and potential product launches for our late-stage programs. In addition, it gives us an opportunity to build our distribution and market access capabilities.

Research and development expenses were $205 million in 2018 compared to $33 million in 2017. The increase was primarily driven by the expansion of our portfolio following the transaction with GSK as well as the continued growth in our R&D and technical operations personnel to support the growing portfolio. Included in R&D expenses in 2018 was a one-time $134 million charge related to in-process R&D on the three clinical programs acquired at the time of the GSK transaction.

SG&A expenses were $31 million in 2018 compared to $6 million in the prior year. The increase was due to personnel and third-party cost to support our public company operations. In addition, the increase included certain cost to support Strimvelis and other pre-commercial activities to prepare for upcoming potential global product launches. For example, the commercial and medical teams are already engaged in efforts to identify patients through newborn screening and perform other disease awareness initiatives.

The growth in our operating expenses led to a net loss of $231 million in 2018. Cash and investments as of December 31, 2018 were $340 million compared to $90 million at the end of 2017. The increase was primarily driven by proceeds from our Series C financing and IPO, both of which occurred during 2018, partially offset by cash used to fund operations and capital expenditures of $102 million. We exited 2018 with the fourth quarter cash burn of $27 million giving you an idea of the quarterly expenditures as we entered 2019.

We expect that our existing cash and investments will enable the company to fund it’s currently anticipated operating expenses and capital expenditure requirements into the second half of 2020. This run rate includes a non-recurring capital cost associated with the build out and equipment at the new Fremont’s California manufacturing facility, which was leased in December of last year.

I’ll end with the summary of our planned 2019 milestones. We’ve released the first of three registrational data sets for our lead programs with the OTL-101 data presentation in ADA-SCID patients last month at ASBMT. And we will be releasing the engraftment data in 10 additional ADA-SCID patients receiving the cryopreserved formulation later this year.

Our second registrational data set for OTL-200 in MLD patients will be presented next week at EBMT with engraftment data in the first three patients receiving the cryopreserved formulation to follow later this year. We are also on track to present a third registrational data set for OTL-103 and WAS patients and beginning enrolling a clinical trial using a cryopreserved formulation.

For patients with X-CGD, we are designing a registrational trial for OTL-102 and plan to engage with regulators on a development path for this exciting program. Recall this program recently provided us with our fourth Proof-of-Concept clinical dataset. We expect to present our fifth potential clinical Proof-of-Concept dataset for OTL-300 and transfusion-dependent beta-thalassemia later this year.

And finally, we are on track for the submission of our clinical trial application in Europe for OTL-201 and MPS-IIIA patients followed by a clinical trial initiation in this second neurometabolic disease.

As Mark said at the start of today’s call, we’ve come a long way towards achieving our vision of building a global, fully integrated pure play gene therapy company dedicated to transforming the lives of patients with rare, life-threatening diseases.

And that closes our prepared remarks. Operator, please open the line for questions?

Question-and-Answer Session


[Operator Instructions] Our first question comes from the line of Anupam Rama of JPMorgan. Your line is open.

Anupam Rama

In the comments when you talked about how there are BLAs before your filing is being planned over the next couple of years. And just wondering within the cash runway going to the second half of 2020, what’s assumed in there in terms of the size and scope of building out the sales infrastructure? And how should we be thinking about that expense run rate heading into the back half of next year?

Mark Rothera

So I’ll hand over to Frank in a moment, but maybe just a couple of points. As we look out to two filings in 2020, so for ADA-SCID in United States, for MLD in Europe, we will be gradually ramping up our commercial effort to prepare for those launches. And so we already have, as you know, the Chief Commercial Officer, we have our Head of US Operations, the Head of European Operations in place and we started to build out key roles within those teams, for example, focused around disease awareness, diagnostic processes, because as you know, in rare diseases patient identification is a very important thing but one has to work hard on in advance of a launch. And so, we will be gradually ramping up. But, of course, you are well aware that in the field of orphan drugs and rare diseases, you really don’t need large teams to do a good job. And I think that’s very much the case. So we will be rightsizing this growth as we approach the regulatory filing and then commercial launch. But, perhaps, I can hand it to you now, Frank, to speak the cash burn as well.

Frank Thomas

Yes, sure. So — yes, embedded in the cash runway, remember that there is some one-time non-recurring costs related to Fremont that are embedded in the ’19 and ’20 guidance. So I do think the burn rate over the next couple of years will be a little bit of higher because of those costs. But certainly, as I think about 2018, I think, we had high single-digit millions invested in commercial and pre-commercial activity. We expect that will ramp up in ’19 and then certainly into 2020 as we prepare for the launch of OTL-101 in the U.S., and MLD in Europe. So we’re not giving you specific numbers, but certainly we do expect from that sort of high single-digit number that to grow. And I think, if you look at commercial organizations of other rare disease companies, it’s going to be pretty representative of how we are thinking about it.


Thank you. Our next question comes from the line of Graig Suvannavejh of Goldman Sachs. Your line is open.

Graig Suvannavejh

I’ve got a couple. One, this one is for Frank. I know you just spoke on kind of how we should think about the commercial spend and how that is going to look over the next couple of years. But you had, obviously, a lot of R&D efforts that are going on as well. So can you help us think about how R&D is going to trend throughout 2019? That’s my first question. And then my second question really has to go to the bridging work that you guys are doing. And from my perspective like there’s a lot of technicalities in that than something that the investors and myself have very little visibility around, could you give us some comfort around the things you are doing to ensure that from your discussions with regulators that you are doing the things that you need to do that would be great. Thanks.

Mark Rothera

So why don’t we begin with the first question on R&D spend, and we will come to your next question. Frank, can I?

Frank Thomas

Yes, let me just get back. I think we started the year with $340 million in cash. We’ve said that gives us runway into the second half of 2020, which includes, of course, an investment in Fremont that won’t be recurring. I think in our public documents, you’ve seen sort of a range of $80 million to $90 million of an investment for that Fremont facility. So the balance of that assumed runway will come from a mix of R&D and SG&A. I think if you look at the second half results for the company that are embedded in one of the tables in the press release, I think, that sets sort of a baseline for what you should expect going into ’19 and into ’20. I do think that as we prepare for commercialization, you will see the SG&A line role leading into those upcoming launches, I think, as some of the additional programs move into the clinic, the R&D line will likely also trend upwards, probably not as much growth from ’17 to ’18 — I’m sorry, from ’18 to ’19 as there was some ’17 to ’18, but we do expect to continue to invest additional amounts in R&D. We do have levers, I think, within the P&L to extend the run way if we need to. But I think we feel that we’ve got a pretty sound plan with plenty of catalysts on the horizon before we would need to go back to the capital markets.

Mark Rothera

And then, maybe to your second question, really we are in a very strong position as you’ve already seen with regard to our lead-through programs, where we’ve already hit the primary endpoints for our registrational trials, and here with our ADA-SCID, MLD and WAS. And we are planning to file within the next three years for those three programs with ADA-SCID and MLD in 2020 and WAS in 2021. So one of the most fundamental points around the bridging question is moving from a fresh formulation product to cryo formulation gene modified stem cells as the product would be commercialized. And as per the icons, just handover to you to say a little bit more about that bridging work and what we are doing?

Frank Thomas

So those three lead programs, which have gone through the wide range of studies, they were generated using a fresh formulation. And we understand the limitation for using fresh formulation and we like others want to launch the commercial products with the cryopreserved formulation as that will give greater accessibility to patients. And the technology and the field is moving in this direction. And also just to reiterate, we’ve actually already treated only 30 patients with cryopreserved formulation across our different studies. So the bridging work is underway for those four, three programs. And what we’re planning to do is to show in vitro CMC comparability between the fresh and the cryopreserved formulation. And we will evaluate the hematopoietic stem cell disease study for cell number, the liability, the sterility of the products and also the VCN numbers in that product as well. In addition to the in vitro CMC composites, we will also look at data from patients who have received the cryopreserved product. And we plan to do it in six months. And what we want to do is to ensure the cryopreserved cells are performing in the same way as the fresh cells. And just, again, just to move on a little bit, at earlier stage product candidate, so those were excellent [Indiscernible] to see transfusion-dependent beta-thalassemia [indiscernible]. Those are all being developed. They are already being developed with the cryopreserved for our formulations. And so this kind of briding work won’t be necessary for those studies.


Thank you. And next question comes from the line of David Nierengarten of Wedbush Securities. Your line is open.

David Nierengarten

I just had a quick one on [indiscernible] and where you were on …

Mark Rothera

David I apologize, but I — we can’t hear your question. Would you mind repeating? We can’t hear it. It’s breaking-up.

David Nierengarten

Is this little better?

Mark Rothera


David Nierengarten

Just a quick question on Wiskott–Aldrich and if there were other things that you needed to do before initiating the cryopreserved trial? And if you had patients identified and essentially ready to go?

Mark Rothera

So I will make an opening statement and hand over to Andrea to say a couple of words on this. So, yes, we are very excited about the WAS program. As you know, this is another area of very high unmet medical need, characterized by severe bleeding and severe infection rates and mortality rate that is quite significant, but at the same time, it’s a quite a large prevalent population. And so it is a large indication is in the rare disease portfolio for us to continue to develop this program into. And one of the key milestones that Frank went through, for this year, will be the sharing of the three-year follow-up fresh formulation data, which we haven’t yet shared fully. And so with that, to just say a little bit more about the cryo formulation trial, I am going to hand over to Andrea.

Andrea Spezzi

Yes. Thank you, Mark, and thank you for the questions. Yes, I am glad to say that the cryo study is opened. It has been initiated. And it’s currently recruiting. So it’s going on track. And hopefully, we will have some data later this year that we will be able at some point to share with you all.


Thank you. And at this time, we’re showing no further questions. I would like to turn the conference over to Mr. Mark Rothera for the closing remarks.

Mark Rothera

So I would just like to thank everybody for having joined us today. And I hope you have seen that really — I think, we’ve achieved a lot in the last 4.5 months since we went public. Just to remind you, we have shared the registration dataset in the 20 patients from the ADA-SCID OTL-101 trial and compared that to natural history or standard-of-care. We have also declared Proof-of-Concept in X-CGD. And you’ve seen interim data on the beta-thal program in the Nature Medicine’s publication. And actually, I would like to share with everybody today that we have also submitted the Proof-of-Concept abstract for this indication to the ASGCT Meeting, which is one of the other milestones that we are talking about for this year. I am also delighted about the progress we are making in the area of technical operations with the appointment of Ran Zheng as Chief Technical Officer, the licensing of the Fremont site and also the deal with SIRION with LentiBOOST as we look at transaction enhancements. And so as both Frank and I said during the call, I think, we’ve really come a very long way to realizing our vision to be a leading gene therapy company dedicated to transforming the lives of patients with rare diseases through our ex-vivo gene therapies. So with that, thank you very much for joining us today.


Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program. You may now disconnect. Everyone, have a great day.