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Autolus Therapeutics Plc (AUTL) Q1 2020 Earnings Call Transcript – The Motley Fool

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Autolus Therapeutics Plc(NASDAQ:AUTL)Q12020 Earnings CallMay 07, 2020, 8:30 a.m. ET

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Autolus Therapeutics first-quarter 2020 financial results and operation highlights conference call. [Operator instructions] Please be advised that today's conference is being recorded. [Operator instructions] I would now like to hand your conference over to your speaker today, Mr. -- excuse me, Dr.

Lucinda Crabtree, vice president of investor relations. Thank you. Please go ahead, ma'am.

Lucinda Crabtree -- Vice President of Investor Relations

Thank you, Carrie. Good morning, and -- or good afternoon, everyone, and thank you for taking part in today's call on the financial results and operational highlights for the first quarter of 2020. I am Lucinda Crabtree, vice president of investor relations. With me today are Dr.

Christian Itin, our chairman and chief executive officer; and Andrew Oakley, our chief financial officer. Before we begin, I would like to remind you that during this call, we will be making forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Our actual results, performance or achievements may be materially different from those expressed or implied by the forward-looking statements.

For a discussion of the risks and uncertainties related to our business and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, please see the section titled Risk Factors in our annual report on Form 20-F filed on March 3, 2020, as well as discussions of potential risks, uncertainties and other important factors in our other periodic filings with the SEC. The forward-looking statements contained in this presentation reflect the company's views as of the date of this presentation regarding future events, and the company does not assume any obligation to update any forward-looking statements. You should, therefore, not rely on these forward-looking statements as representing the company's views as of any date subsequent to the date of this presentation. So with that, on Slide 3, you will see the agenda for today, and it is as follows: Christian will provide a brief introduction, and that will be followed by our operational highlights for the first quarter of 2020.

Andrew will next discuss the company's financial results, and then Christian will conclude with upcoming milestones and other concluding comments and, of course, we welcome your questions following our remarks. So with that, I'd like to now turn the call over to Christian. Thank you.

Christian Itin -- Chairman and Chief Executive Officer

Thank you, Lucinda, and welcome to all of you, and thank you for joining us. I'm pleased to review our progress for the first quarter in 2020. First, on Slide 5, we are pleased to report on a very productive first quarter. We remain on track with our clinical programs, despite the challenges of COVID-19.

As an organization, we have quickly adapted to this very challenging environment, ensuring business continuity. Our focus has been on ensuring our clinical B-cell programs, AUTO1 and AUTO3, continue to progress, and we remain on track with recruitment ongoing and manufacturing operations uninterrupted. As such, we expect to deliver data in the time lines that we have previously guided. While some of our participating clinical centers have been an infection hotspots and had to pause enrollment for a few weeks, others could continue to work unimpacted.

We expect infections will continue throughout the year with flare-ups in places that were hit by the first wave of infections, while the areas spared for now may see a rise in infections at some point in the upcoming months. However, what is important to remember is that the patients we enroll in our trials have a very high medical need, no different from a severe COVID-19 patient and the drive for centers to continue to treat these cancer patients is very high. Typically, if a center gets under heavy pressure from COVID-19 infections, stem cell transplants and CAR-T therapy are among the last procedures to be stopped and are among the first to resume the post-peak infection. As many of you have analyzed, the tie from establishing social distancing and stronger measures to reaching the other side of the first infection peak has in all impacted areas taken approximately eight weeks, irrespective of whether the measures were taken early or late relative to the rise of infections.

The consistency of this infection pattern is helpful to anticipate the time of impact on a given center and catchment area. Finally, we expect the increasing levels of preparedness and adjustments under way in the various healthcare systems, and the continued implementation of social distancing measures that will allow for continued treatment of these severely ill patients throughout the year. We expect that the adjustments we made for clinical trial operations and in our supply chain will remain relevant and in place for the duration of this infection cycle, plus the wider operational adjustments we made to minimize risk of infection and exposure as well as increased resilience toward the risk of business interruptions will also remain in place and, if necessary, will be adjusted. With regards to our earlier-stage programs, we are monitoring potential impact.

At this point, we may see up to a quarter of delay depending on the program and the impact COVID-19 had on our respective academic or business partners. With that, and remaining on Slide 5, let me give you an overview of our corporate highlights. We announced in April that the FDA accepted the IND application for AUTO1, our lead CAR-T product candidate, for the treatment of adult patients with acute lymphoblastic leukemia, which allows us to initiate clinical sites in the company's first pivotal study, AUTO1-AL1 in the U.S. This followed up the opening of the first site in the U.K.

in March of this year, having received approval of the clinical trial applications by the MHRA earlier in the quarter. We expect to initiate dosing of our first patient in this study this quarter, and remain on track to provide full data by the end of 2021. With regards to our lead product candidate for the treatment of DLBCL AUTO3, the Phase 1/2 ALEXANDER study is ongoing. The timing of the program remains on track, and we will update on the decision for Phase II in mid-2020, as previously guided.

We're excited about our DLBCL program and its broader market potential, following the positive data update we provided at the EHA-EBMT CAR-T Cell Meeting in February 2020. Our Chief Scientific Officer, Dr. Martin Pule, presented early encouraging signs of sustained complete responses we've achieved with low toxicity and minimal patient management required. We're now planning to add a 20-patient cohort to the ongoing ALEXANDER study in second half of this year, with patients treated in an outpatient setting, which I will explain -- expand on a little later in this call.

The last item I wish to touch on in this slide is our forthcoming clinical data updates expected through May and June. For AUTO1 in adult ALL, we plan to present updated data at the virtual EHA Meeting in June with approximately six months of additional follow-up post our ASH 2019 data cut. For AUTO3, we are planning to present these updated data at ASCO in an oral session. We will also follow up with a similar presentation at the EHA Meeting two weeks later.

We plan to present both sets of data to investors in calls shortly following these virtual conferences. Moving to Slide 6, in addition to our two lead clinical candidates, we're planning a series of preclinical data updates on some of our pipeline programs at AACR II in late June. We have been invited to make an oral presentation in our prostate cancer program AUTO7 and and also have poster presentations planned for both AUTO6NG in small cell lung cancer as well as AUTO5 assisted program to the AUTO4 in T-cell lymphoma. Much like ASCO and DHA, we're planning an investor call that will shortly follow these presentations at AACR II.

Finally, I would like to thank our partners at the cell therapy, Catapult, and the GSK site organization in Stevenage for their continued support that enabled us to maintain operations throughout the peak of infection and support the critically ill patients in our trials. Moving to Slide 7, I wanted to spend a brief moment recapping on our lead program AUTO1 in adult ALL. Relapsed/refractory adult ALL is a challenging disease and often impacted in elderly patients. A lot of these patients have significant comorbidities, making them a fragile patient group to treat.

The indication is approximately three times the size of relapsed/refractory pediatric ALL and represents an attractive market opportunity. Within the U.S. and the top five European countries, approximately 3,000 patients every year are at an end stage of treatment, having failed chemo and transplant and, therefore, requiring other options. At this point, there's no CAR-T therapy approved for adult ALL.

Obviously, there are a number of programs that are being tested. However, all of them have experienced significant challenges with the management of the toxicities. And what we created with AUTO1 is a product that is designed to behave physiologically and engages target cells like a normal T-cell would. First generation CAR-T products share the identical binder to CD19, this is true for Kymriah to start to analyze the cell.

This binder has a slow off-rate from the CD19 target. And as a consequence, once the CAR-T cell binds to the leukemia cell and has delivered the cytotoxic payload, it has difficulty letting go from the target cell and get stuck. When you have a CAR-T cells -- when you have CAR-T cells getting stuck to target cells, they continue to be activated, which drives cytokine release and thus adverse events. In addition to leading to cytokine release syndrome, this continued activation of the CAR-T cells can drive exhaustion, which negatively impacts persistence.

So there's a real fundamental challenge with that type of engagement. In contrast, what we created with AUTO1 is a CAR-T product that mimics the behavior and the binding kinetics of a physiological T-cell with a very fast off-rate and an ability to disengage relatively rapidly after delivering the kill. The result is reduced cytokine release and also an increase in target cell killing as the CAR-T cells are freed up more quickly and can reengage new leukemia cells. In addition, CAR-T cells can expand more readily, that's leading to more active CAR-T cells in the patient's body capable of fighting the leukemia.

Now turning to Slide 8, what we show on the left-hand side is the data for blinatumomab, or Blincyto, which is also the current standard of care in this disease setting. What is important to understand is that the patients that we have treated on our trial that we highlighted and what we highlighted at ASH is that the patients have mostly undergone and failed stem cell transplant. In addition, approximately 60% of patients have been on inotuzumab or blinatumomab and failed. So our data is based on a patient population with more advanced disease compared to the data shown for blinatumomab.

However, what you see in the blinatumomab results is that our CR rate in that population is about 40% with an event-free survival of about 30% at six months. And in fact, most patients relapse within less than a year. When we look at the safety profile, Blincyto shows a good safety profile overall. And in fact, the product is typically delivered in an outpatient setting.

Now when we look at our own data for AUTO1, if you look at the total data set of 16 patients, we have an overall CR rate of 87%, and they have an event-free survival of 68% at six-month level. So in a simple way, we have around twice the activity that was reported with blinatumomab with a comparable safety profile. We have had no patients with high-grade cytokine release syndrome. We have 19% of the patients with high-grade neurotoxicity.

All patients with high-grade neurotoxicity had a very high tumor burden in the marrow of more than 50%. Going forward, we will manage these patients when the neurotoxicity starts to build to minimize high-grade adverse events. Finally, I just wanted to touch on the subset of patients that were treated with the closed commercial manufacturing process. You can see that the data, if anything, looks somewhat better than the total of overall, which includes patients that were treated with product that was manufactured by hand with a conventional manufacturing process.

So based on this data, I'm turning to Slide 9, we decided to move the program forward into a pivotal study. The CTA was filed in the U.K. and cleared in Q1, and we're enrolling currently in the U.K. The U.S.

IND also is now open, and we're opening up these centers in the U.S. with the aim of enrolling patients in the second quarter. As a reminder, this is a single-arm 100-patient study of relapsed/refractory patients. The primary endpoint is CR rate, and secondary endpoints include molecular CRS event-free survival and duration of response.

We remain on track to complete enrollment in the first half of next year. To what extent we may be impacted by the COVID-19 situation going forward, we'll have to see, but we currently expect the impact to be limited. Our plans to deliver data by the end of 2021 remain on track. Let's now turn to Slide 10, where I would now like to switch gears and talk about AUTO3, a program that is designed for the treatment of patients with diffuse large B-cell lymphoma.

Third line DLBCL is about four times bigger an indication than relapsed/refractory adult ALL and a setting with already two approved CAR-T therapy products with Yescarta and Kymriah plus liso-cel, or JCAR-17, expected to be approved later this year or beginning of next year. We know this is a large opportunity with approximately 10,000 patients in the back end of the disease, which is a sizable population with a very significant medical need. In terms of the outlook for those patients, they have typically run through a series of chemotherapy combinations often with a monoclonal antibody, and they also have received the transplant if they were eligible for it. If not, they go directly to salvage therapy.

CAR-T therapies are approved in the third line of salvage therapy setting in trials ongoing in patients in second-line setting. There are two things that we see as being really important for successful treatment and commercial uptake in DLBCL. First, you have to induce complete remissions that are lasting. This is a disease setting where you aim for cure.

Second is that you actually have to have a therapy that can be administered where our patients are situated. Today, in the U.S., approximately 80% of the patients are treated outside of university hospitals and only about 10% of the patients are treated as university hospital in-patients. It is this population that is primarily treated with CAR-T therapies. The key challenge for treatment centers is the need for intense patient management, which has the limited use of CAR-T outside of the university hospital in-patient setting.

What we're looking for in AUTO3 is a high level of sustained complete remissions. In addition, we're looking for a safety profile that can be managed in nonacademic outpatient settings to reach the majority of patients. Moving to Slide 11, across the CAR-T populate -- programs in DLBCL, we observed a fairly high overall response rate, yet the sustained complete response rate is limited. It is somewhere between 30% and 40%, depending on the program and the subset of indications that were treated or included in the respective trials.

Roughly 1/3 of the complete responses are lost early on, typically within the first three to six months. There are two key mechanisms reported that are likely driving relapse. Loss of CD19 antigen in about 30% to 50% of the patients at time of relapse and PD-L1 checkpoint upregulation in about two-thirds of our patients at time of relapse. Looking at safety.

With the commercial CD19 CARs, there's a significant amount of management of those patients required to address severe cytokine release syndrome and, in particular, as well as the severe neurotoxicity. Typically, these toxicities have an early onset and require intense patient management and monitoring, meaning patients are largely confined to a classical hospital in-patient setting. We designed a program with a dual targeting approach having two independent receptors in each CAR-T cells, individually designed and optimized for the respective target antigen to minimize the impact of CD19 antigen loss. We also gained at the PD-L1 upregulation and checkpoint based scope of lymphoma cells with a single dose of pembrolizumab on the day before infusion of AUTO3, providing the cover to achieve a CR and sustain it.

AUTO3 has shown a high level of CRs in the dose escalation phase of the current study, and we will present a further update at ASCO. It is worthwhile noting that the high level of complete remissions were obtained without inducing high-grade CRS, or cytokine release syndrome, and no neurotoxicity of any grade in the patients dosed at 150 million to 450 million cell doses, and this is a very unusual finding. When you compare this profile with Yescarta, Kymriah and JCAR-17 data, the contrast is remarkable. What is also important to note is that with AUTO3, we have not managed the patients actively for adverse events.

Now to talk about the extent of the total addressable market, this profile enables us to potentially reach, let's continue to Slide 12. Currently, our approved products are only tapping into a proportion of substantially less than 20% of the market opportunity, which is managed by the academic centers. There's very little to no penetration to the remaining 80% of the market, which comprises settings that we cannot deal with the intensity of patient management required for the current CAR-T products. We believe this creates an enormous opportunity for the profile of a product that we're seeing with AUTO3.

And as such, we believe that the program has a unique potential going forward. We expect to provide an updated ASCO on the clinical profile of the program. So let us turn to Slide 13, where I would like to outline how we continue to build on this potential patient profile. Given the highly differentiated clinical and safety profile we have reported so far, we see an attractive opportunity for AUTO3 as an in and outpatient solution for patients with DLBCL, therefore, maximizing that commercial potential of CAR-T products all across the settings of care in this disease.

As such, we're planning to add a 20-patient cohort to our ongoing Phase 1/2 ALEXANDER study in the second half of this year, with patients treated in an outpatient setting in order to broaden our understanding of the feasibility of outpatient administration. With that, I will turn over the call to Andrew for our first-quarter 2020 financial update. Andrew?

Andrew Oakley -- Chief Financial Officer

Thanks, Christian, and good morning or good afternoon to everyone. If we move to Slide 15, it's my pleasure to review our financial results for the first quarter of 2020. Net total operating expenses for the three months ending March 31, 2020 were $38.6 million. That was net of grant income of $300,000.

And that compares to net operating expenses of $30.2 million, net of grant income of $2 million for the same period in 2019. The increase was due, in general, to our continued increase in clinical trial activity which is expected to deliver on key milestones throughout the rest of 2020; also increased headcount; and an increase in public company costs, primarily related to insurance. Research and development expenses increased to $31.3 million for the three months ended March 31, 2020, and that's up from $22.6 million for the same period in 2019. Cash costs, which also exclude depreciation and amortization as well as share-based compensation, increased to $25.6 million from $17.5 million.

The increase in R&D cash costs, that's $8.1 million, consisted primarily of an increase in some compensation-related costs of $2.2 million due to an increase in employee headcount that supports the advancement of our product candidates as well as an increase of $3.7 million in project expenses associated with a clinical activity. And that includes the research, process development, manufacturing activities necessary to conduct the studies. Plus an increase of $1.8 million in licenses, legal fees and consulting services, which -- some of which is related to an option to negotiate a future license as well as the IT infrastructure and support. The remainder was attributable to other additional costs in the amount of about $400,000.

General and administrative expenses decreased to $7.6 million for the three months ending March 31st, and that's down from $9.6 million for the same period in 2019. Cash costs, again, which exclude depreciation as well as share-based compensation, decreased to $5.9 million from $6.3 million. Compensation-related expenses decreased by $300,000 and IT, communication -- telecommunication and general office costs decreased by the same amount and a decrease also of the same amount in commercial costs, but -- that was all offset by an increase in public company costs of around $0.5 million, which primarily relates to insurance, as I have previously mentioned. Net noncash costs within the G&A area decreased to $1.7 million for the three months ending March 31, and that compares to $3.3 million for the same period in 2019.

The decrease here is attributed to basically share-based compensation expense, which decreased by $1.6 million as a result of the lower value of the stock options that were recognized during the period. The net loss attributable to ordinary shareholders was $29.9 million for the three months ending March 31, 2020, and that compares to $27.2 million for the comparable period in 2019. Cash and cash equivalents at the end of the quarter totaled $243.3 million, and that compares with $210.6 million that we had at the end of December 2019. As such, we anticipate that, that cash on hand provides us with a runway into 2022.

And with that, I will now hand the call back to Christian to give you a brief outlook on expected milestones. Christian?

Christian Itin -- Chairman and Chief Executive Officer

Thanks, Andrew. Let me conclude this part of the management discussion with a review of the upcoming milestones and news flow through 2020. Let's move to Slide 17. The upcoming eight months will be an end full period for us with multiple clinical milestones and opportunities for value creation.

Our chief and most imminent operational focus is to conduct these, obviously, our pivotal trial for AUTO1 in adult ALL. We expect to report clinical data across multiple programs, including updated AUTO3 ALEXANDER data at the forthcoming ASCO Meeting and updated AUTO1 or CAR19 data as well as AUTO3 data at EHA, as previously mentioned. We will look to progress a number of our other preclinical candidates through the second half of 2020 and are looking forward to providing preclinical data updates in our solid tumor programs AUTO6NG and AUTO7 at AACR as well as our T-cell lymphoma program with AUTO5. Finally, toward the end of the year, and we look forward to providing further data updates on both AUTO1 and AUTO3, as we expect for the end of the year.

In conclusion, on Slide 18, I'd like to recap the major message raised from today's call. First AUTO1 is our first Autolus' program to move into pivotal stage. Given the positive safety and efficacy profile today, we believe that AUTO1 has the potential to be a best-in-class CD19 CAR-T program in adult ALL, a disease setting with a very high unmet medical need. Secondly, with regards to AUTO3 and DLBCL, which is expected and slated for additional clinical data updates at the ASCO and EHA.

We plan to conduct an outpatient cohort in the second half of this year. The company is in an excellent position, combined with a strong balance sheet, which provides us a run rate into 2022. We feel we're in a good position. I think are looking forward to an exciting second half of the year.

We're now happy to take questions. Thank you.

Operator

[Operator instructions] Your first question comes from the line of Chad Messer with Needham & Company.

Unknown speaker

Hi, everyone. This is Joe on for Chad. And congratulations on the progress in a difficult environment. So just a couple of questions from me.

You discussed kind of the challenges that are related to DLBCL. And hypothetically, what would you consider more important, patient accessibility or the duration of and deepness of response?

Christian Itin -- Chairman and Chief Executive Officer

Well, thanks a lot for joining, really appreciate it. The -- I think with regards to DLBCL, you want -- you need both aspects actually to be addressed. You need a high level of sustained CRs and you need an excellent safety profile to reach the population. Both aspects are important, and we believe that we have an ability to make a significant improvement on both sides of the program.

Unknown speaker

So you do not consider one more important than the other in this instance?

Christian Itin -- Chairman and Chief Executive Officer

Well, there's -- it is -- it's a life-threatening disease. The first thing you have to make sure is you -- the patient survives. So getting to a long-term remission is what the ultimate goal is, but then you also have to make sure that the patient has access to the therapy. And right now, in the U.S., there are only about 10% of the patients in that disease setting that has access to CAR-T therapy because it is confined to the inpatient segment of the centers of excellence.

And that has actually created a situation where while there is a big demand for these types of therapies, the actual access that can be realized is very, very small. And that is all on the actual intensity of the management of these patients during the adverse events that occur in the -- at the onset of the therapy. And that is sort of the key reason for the confinement to this relatively small number of centers. So you have to make fundamentally have the impact on the disease.

That is what the sustained CR rates give you, but then you actually have to have a safety profile that allows you to further expand the delivery of this type of therapy to centers beyond the relatively small numbers of academic centers of excellence.

Unknown speaker

All right. All right. Thank you.And we are very much looking forward to seeing some of the preclinical data at the second half of AACR. I noted that it looks like the AUTO6NG data would be presented in small cell lung cancer.

So that's a very interesting indication, not just because of the target, but also because of the lack of immunogenicity that's seen in a lot of these cells. Kind of maybe you could kind of orient us what kind of data we should be expecting at AACR?

Christian Itin -- Chairman and Chief Executive Officer

So at AACR, what we're going to be presenting are obviously a preclinical data on these -- from these programs. As you may remember, the way we designed the programs is actually to include a set of cell programming modules that enable the cells to have a higher resilience and higher ability to cope with the challenging microenvironments that we find in these particular sets of tumors. I believe that is going to be a key part of the data that we're going to be presenting is the use of those modules in those settings and the impact the modules have to actually give us an appropriate level of activity in these, as you point out, very challenging tumor environments.

Unknown speaker

Excellent. Then -- and just some kind of a last clarification. You're expecting to complete enrollment in the pivotal study by year-end '21 or [Inaudible]

Christian Itin -- Chairman and Chief Executive Officer

First half next year.

Unknown speaker

First half next year?

Christian Itin -- Chairman and Chief Executive Officer

First half next year with data at the year-end, next year.

Unknown speaker

OK. Thank you. That's what I thought. Thank you for taking my questions, and congratulations on your progress.

Christian Itin -- Chairman and Chief Executive Officer

Thanks a lot. Thanks for joining.

Operator

Your next question comes from the line with Mara Goldstein with Mizuho Securities.

Mara Goldstein -- Mizuho Securities -- Analyst

Thanks very much for taking the question. If I could just ask on the AUTO3 outpatient program, can you just talk a little bit about what the profile of that patient would look like relative to inpatient within to the content -- to the extent that you can discuss protocol on that basis? And then just also if I could drill in a little bit on the sort of go, no-go decision as well expected later in this year and the decision tree that will help you get to making that decision, if you could discuss that?

Christian Itin -- Chairman and Chief Executive Officer

Yes. Hi, Mara, thanks for joining. So in terms of the patients, the patients actually, we don't expect to look different from the patients that we've treated so far. The reason why you treat the patients in an inpatient setting with the current CAR-T programs is not because of the state the patient is in, but it is the consequences of the toxicity induced at the onset of the therapy that you're providing.

So there is not a -- and we don't expect to see a difference in the patients. And in fact, as you can imagine, with the majority of the patients treated outside of the academic centers, the patients are in a reasonable condition and can obviously normally manage -- be managed in oncology clinics and networks, et cetera, much more in the periphery of the healthcare system. So we expect the same patients, but obviously, we're treating them in a slightly different setting than what the inpatient setting is. So this is not a difference of the patients, it's a difference on the level of patient management that's required to actually get these patients safely through the therapy.

And that is what the profile of AUTO3 is actually enabling us to explore.

Mara Goldstein -- Mizuho Securities -- Analyst

OK. Thank you.

Christian Itin -- Chairman and Chief Executive Officer

And then with regards to decision points, obviously, we're going to provide an update of where we are with the program at ASCO. That gives us a very good view on the response rate level. We will have additional follow-up that we'd like to see, which gets us into -- slightly into the second half of the year that, at which point, we'll understand what the sustained CR rate looks like. And that will be the key piece of information that will inform us on the path forward.

And as you can imagine, getting the data from the outpatient cohort would also enable us to actually design a pivotal study somewhat differently, including outpatients -- an outpatient setting in the pivotal study as well, which we believe it would actually be a very important component of the pivotal program. So that data will be very informative in terms of the design of the study as well.

Mara Goldstein -- Mizuho Securities -- Analyst

OK. Thank you. I appreciate it.

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Autolus Therapeutics Plc (AUTL) Q1 2020 Earnings Call Transcript - The Motley Fool

Combating coronavirus: UAE announces its highest ever recoveries in a day – Khaleej Times

Dr Amna Al Dahak Al Shamsi, official spokesperson of the UAE Government, said 25 per cent of all Covid-positive patients have now recovered.

The UAE has recorded 458 Covid-19 recoveries in a single day - its highest ever. This brings the total number of recoveries in the country to 4,295.

Dr Amna Al Dahak Al Shamsi, official spokesperson of the UAE Government, said 25 per cent of all Covid-positive patients have now recovered. The UAE has 12,937 Covid-19 active cases.

The official announced 624 new infections after 33,155 more tests were carried out. She also announced 11 deaths, taking the toll to 185.

Dr Al Shamsi attributed the increase in recovery cases to the proactive measures being taken in the country. "We call on the public to cooperate with the health authorities and to continue adhering to all precautionary measures, including staying at home, social distancing protocols and wearing of face masks."

Meanwhile, on Friday, His Highness Sheikh Mohamed bin Zayed Al Nahyan, Crown Prince of Abu Dhabi and Deputy Supreme Commander of the UAE Armed Forces, ordered payment of all costs related to treatment of critical cases of coronavirus through stem-cell therapy. The initiative comes after the Abu Dhabi Stem Cell Center (ADSCC) announced development of an innovative and promising treatment for Covid-19 infections using stem cells.

ismail@khaleejtimes.com

Ismail Sebugwaawo

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Combating coronavirus: UAE announces its highest ever recoveries in a day - Khaleej Times

Orchard Therapeutics (ORTX) Q1 2020 Earnings Call Transcript – Motley Fool

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Orchard Therapeutics(NASDAQ:ORTX)Q12020 Earnings CallMay 9, 2020, 8:30 p.m. ET

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Orchard Therapeutics First Quarter 2020 Investor Conference Call. [Operator Instructions]

I would now like to hand off the conference over to your speaker today, Renee Leck, Director of Investor Relations. Please go ahead, ma'am.

Renee T. Leck -- Director, Investor Relations

Thanks, Sonia. Good morning, everyone, and welcome to Orchard's First Quarter 2020 Investor Call. You can access the 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 and uncertainties, and including those set forth in our annual 10-K filed with the SEC and any other filings we may make. 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 our CEO, Bobby Gaspar.

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Thanks, Renee. Hello, everyone, and welcome. I'd like to start by first acknowledging the tremendous efforts of our organization and our partners in the healthcare field to ensure patients in need continue to receive care during this difficult time. Thank you, everyone. The last few weeks have been an important period for Orchard. Since taking on the leadership, Frank and I, together with the executive team, have thought very carefully about what the new Orchard can become, how we can ensure that Orchard can fulfill its true potential and what we need to do to make that happen.

When we think about our strategic vision as a company, it's really all based on the potential of the hematopoietic stem cell gene therapy platform, where it can take us and the benefit it can provide for many patient populations even beyond our current portfolio of ultra-rare diseases. We have taken some bold and decisive actions that we believe will allow Orchard to achieve long-term growth and focus the company on sustainable value creation. This vision is supported by a new strategic plan that we have developed and which is built around four pillars. Each of these forms a chapter in our remarks this morning.

First, operating efficiencies. We have made a series of important changes to our operations that will enable us to sharpen our focus and more efficiently execute our strategy, which I will detail in a moment. Second is our commercial build. We are focused on establishing the right model for the diagnosis and treatment of patients undergoing HSC gene therapy, and see the true value of this approach over a series of ultra-rare products. Third, one of the most exciting areas in gene therapy right now is the innovation taking place in manufacturing technologies that have the potential to deliver economies of scale. We want to be leaders and invest in this space, knowing that our near-term capacity needs are covered by our experienced CDMO network.

Finally, central to this strategy is prioritizing our portfolio to enable the expansion of Orchard's pipeline beyond ultra-rare to less-rare indications. We are disclosing two new research programs for the first time today, and these are a genetic subset of frontotemporal dementia or FTD, and a genetic subset of Crohn's disease. We believe that the biological and clinical validation that has already been shown in our ultra-rare indications allow us to expand with confidence to these larger indications.

Turning to the first chapter in our new strategic plan. We are focused on improving the operational efficiency throughout the organization. This started with an extensive evaluation over the past six weeks of each program in our portfolio using several criteria that are shown here on the left-hand side of slide five. We undertook an objective analysis that involved both financial metrics and strategic considerations in identifying those programs where there was high need for patients and high-value creation for shareholders. As you can imagine, these were difficult decisions given the potentially transformative nature of many of these programs. Each has value, and we intend to realize that in different ways and over different time horizons.

Today, however, we believe our resources are best focused on Metachromatic Leukodystrophy, Wiskott-Aldrich syndrome, the MPS programs and our research programs. This also means that we have a balanced portfolio with late, mid and early stage programs. The programs I haven't mentioned such as OTL-101 and ADA-SCID and the transfusion-dependent, beta-thalassemia program, OTL-300, will have a reduced investment moving forward. We will look for alternative ways to realize value with those programs, including through partnerships.

So slide six brings together a summary of the operational changes that we've announced today. We believe these changes were important and necessary to enable Orchard to execute its mission and objectives at the highest level by matching our attention and resources to a set of core imperatives for the business. As summarized here, we expect to realize cash savings of approximately $15 million from the prioritization of our portfolio. Another $60 million in savings results from the decision to consolidate our R&D teams to one site and defer the investment in the manufacturing facility. Finally, the more staged approach to the commercial build-out and 25% reduction to our existing workforce and future headcount planning will each yield another $25 million in savings.

All of these cash savings are expected to be realized over 2020 and 2021, and result in total expected savings of $125 million over that period. With the revised plan, we now have cash runway into 2022 and no near term need to finance. It's worth briefly mentioning that this $125 million savings is after making investments in the following key areas to support our new strategy, shown on slide seven. In commercial, diagnostic and screening initiatives, including no-charge testing programs to help identify patients with MLD and other neurodegenerative conditions in time for treatment. In manufacturing, the technology, process innovations and efficiencies to drive scalability.

In R&D, initiatives in less-rare diseases that have the potential to fuel the company's future growth in a substantial way. This wasn't just an exercise to reduce expenses, but important decision-making to ensure our capital is deployed in a disciplined manner, while building a pipeline that can leverage our success across all phases of our business.

Now let me turn the call over to Frank to discuss additional key elements of the new plan.

Frank Thomas -- President and Chief Operating Officer

Thanks, Bobby, and good morning, everyone. As you can tell from this morning's press release, we have carefully examined each aspect of our business. You heard that a moment ago from Bobby, with the way we are creating operational efficiencies, and I think you will see additional evidence in the next two sections as we summarize our latest thinking around commercial deployment and manufacturing. Starting with commercial. We understand the importance of developing a commercial model that will demonstrate our ability to execute and bring these therapies to the market successfully. This model and the infrastructure that we build will also be leveraged for any future product launches.

As you'll note from the bottom of slide nine, each rare disease has certain dynamics that will impact the launch trajectory and speed with which we can penetrate the market. In fact, we anticipate our first two potential launches in WAS and MLD having distinct but complementary launch curves, as you can see from the illustrative diagrams. Let me start with MLD on the left, where we expect to launch first in the EU, followed by the U.S. and then other countries around the world. We think an important inflection point on the revenue curve with MLD will come later when newborn screening is established, providing an opportunity for an acceleration in growth rate. Disease progression is a second important dynamic that will affect market penetration. Because MLD advances so rapidly, it will be important to diagnose patients early and get them treated.

For Wiskott-Aldrich syndrome, the dynamics are very different, and it's reflected in the shape of the curve on the right. Unlike MLD, this disease is slower progressing and more readily diagnosed. We believe that WAS will provide an opportunity to treat a number of prevalent patients from the outset and also give us additional long-term revenue stream. This program, the BLA and MAA filings are on track for 2021. Turning back to MLD for an update on the regulatory time line. We are on track to get a decision from the European Medicines Agency later this year, and if approved, launch in the EU in the first half of 2021.

In the U.S., we recently engaged with the FDA on our planned BLA submission of OTL-200 for the treatment of MLD. The FDA has provided written feedback on the sufficiency of the company's data package, including the clinical endpoint, the natural history comparator and the CMC data package. As a result of this feedback, we intend to file an IND later this year and also seek RMAT designation, both of which we believe will facilitate a more comprehensive dialogue to discuss the data more fully and resolve the open matters before submitting a BLA. We are committed to working closely with the agency, and we'll provide updated guidance on the new filing time lines for the BLA after further regulatory interaction.

On slide 10, you can see that we're tracking nicely for the launch of OTL-200 in the EU in the first half of 2021, if approved, with Germany being the first country where we expect to treat commercial patients. Many of the prelaunch activities are under way, and the team has been able to keep up momentum during the pandemic to work with key centers and progress with site qualifications. We intend to set up a network of treatment centers where MLD patients are often referred and who also have transplant expertise. These same centers can be leveraged in future launches, especially for programs in the neurometabolic franchise.

I previously mentioned the importance of diagnosis in MLD to identify patients at early stages of disease, and we are taking the necessary steps to achieve long-term success. Beyond typical disease awareness efforts, we are also looking at initiatives such as no-charge diagnostic testing with partners such as Invitae, and we are looking to facilitate newborn screening for MLD with funding of upcoming pilots in New York State and Italy that are designed to validate the assay and provide the data for wider implementation. Success in these key initiatives will support early MLD patient identification.

Coming up quickly behind MLD and the neurometabolic franchise, our two proof-of-concept programs in MPS disorders, where we have made recent progress even during this challenging period with COVID-19. For MPS-I, over the past year, we've shown promising preliminary proof-of-concept data with positive engraftment, biomarker correction and encouraging early clinical outcomes, and we are excited to announce our plan to begin a registrational trial next year, bringing this program one step closer to commercialization.

For MPS-IIIA, we announced late last month that the first patient was treated in a proof-of-concept trial at Royal Manchester Children's Hospital, with enrollment planned to continue this year and interim data to be released in 2021. You can see graphically on slide 12 how the aggregation of these commercial markets lead to sustainable revenue growth. In addition, the infrastructure build is designed to provide the necessary commercial capabilities to realize the potential of the portfolio. On this slide, we've included the incidence figures for MLD and the incidence and prevalence figures for WAS to help you understand each opportunity as we see it today.

Given the dynamics at play for MLD that I described on slide nine, we believe this opportunity should largely be tied to the incident patient population, which we believe ranges from 200 to 600 patients per year in countries where rare diseases are often reimbursed. We've taken a more conservative view than previously on the addressable patient and market opportunity in countries such as those in the Middle East and Turkey, where the literature has a wide range of differing incident figures. Also, over time, with improved disease awareness, there may be prevalent patients identified who also could benefit from therapy. Our commercial strategy has always been and continues to be based not only on one product, but rather the aggregation of multiple potential products launching off one HSC gene therapy platform and infrastructure.

Turning to manufacturing. We've also made some key changes to our approach in manufacturing and how we allocate capital in the short and mid-term. On slide 14, you'll see the main tenets of our new manufacturing strategy. First, in the near term, we plan to focus on innovative technologies to enable commercial scalability.

Second, to ensure the appropriate focus on those technologies, we've made a decision to consolidate R&D to a single site in London, which brings together our organization in a more efficient way. This will allow efforts made to improve our manufacturing processes to be quickly and easily shared and then scaled commercially to transfer to our third party manufacturers, all of whom are currently located in Europe. As part of this consolidation, we will close our California site, including the termination of the Fremont project and associated capital spend.

Third, we have strong relationships with CDMOs that will ensure supply of clinical and commercial product to satisfy near-term requirements. And longer term, we intend to identify a new site in the U.S. to eventually bring manufacturing capabilities in-house with a facility that is appropriately sized and fitted for future techniques and operations.

Slide 15 shows the three phases of our approach in manufacturing: invest, partner and build. Today, we are investing, and we'll continue to invest in technologies such as transduction enhancers, stable producer cell line and closed automated processing of the drug product. This will potentially reduce the amount of vector needed, drive down COGS and potentially change the way products are manufactured, making it less labor-intensive, less expensive and more consistent. In the near and mid-term, we will continue to rely on our manufacturing partners for the early planned launches in MLD and WAS. For example, MolMed has been with these programs since the beginning, and they've been a reliable commercial partner with Strimvelis.

In addition to our existing CDMO network, we have begun to search for a drug product partner in the U.S. to complete a tech transfer and serve the U.S. market, thereby reducing scheduling challenges and creating some redundancy. And finally, over time, we plan to build in-house manufacturing capabilities closer to when there is a need for additional capacity. This enables us to explore options that are more aligned with our business in terms of scale and timing.

And with that, I'll turn the call back over to Bobby.

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Thanks, Frank. In this section, I'm going to briefly highlight the potential of HSC gene therapy to correct not only blood lineage cells, but also how through natural mechanisms, specific cell types may allow correction of disease in specific organ systems and enable expansion of our portfolio into new research indications. As many of you know, and as shown on slide 17, through HSC gene therapy, we are able to insert a working copy of the gene permanently into the genome of HSCs, and these genetically modified cells can lead to multiple corrected cell types in the bloodstream, including immune cells, red blood cells and platelets.

In addition, HSCs can differentiate into cells of the monocyte macrophage lineage that naturally migrate into various organ systems, and thus gives us an opportunity to deliver genes and proteins directly to those organs, including the brain and the GI tract. Within the neurometabolic space, in particular, we have understood through our preclinical and clinical programs in MLD, MPS-I and MPS-IIIA how HSC gene therapy can deliver genes and proteins to the CNS to correct neurodegeneration. Here is an example of this natural mechanism at work in slide 18.

Data shows that there are a population of gene-modified HSCs that can naturally cross the blood-brain barrier, distribute throughout the brain, engraft as microglia and express enzyme that is taken up by neurons. We have seen this approach results in clinical benefits for patients with MLD, and we are also using the same approach for MPS-I and MPS-IIIA. Beyond this, we see that the HSC gene therapy approach could be used to deliver specific genes and proteins for other larger neurodegenerative conditions which have high unmet need.

One of the conditions we are disclosing today, and shown on slide 19, is a specific genetic subset of frontotemporal dementia, where the underlying pathogenesis has a number of parallels with the neurometabolic conditions that we are already addressing. This program involves a broad strategic alliance with Dr. Alessandra Biffi, Boston Children's Hospital and Padua University in Italy, to further explore the potential of ex vivo HSC gene therapy in neurometabolic and neurodegenerative conditions. In other organ systems, such as the GI tract, there are similar mechanisms at work which are illustrated on slide 20. Tissue resident macrophages in the gut wall are required to respond to bacterial invasion from the gut lumen and prevent infection. In certain disorders, such as X-linked chronic granulomatous disease or XCGD, defects in macrophage function results in an abnormal immune response and severe colitis.

Moving on to slide 21. We have already seen in our XCGD program the modification of HSCs and migration of gene-modified cells into the gut can lead to resolution of colitis through presumed reconstitution of the immune response. Certain subsets of Crohn's disease are also associated with mutations in genes that affect the response of macrophages to infection, and so our clinical observations that HSC gene therapy for XCGD suggest that the same approach may be applicable to this genetic subset of Crohn's disease. This preclinical work is ongoing in our Orchard research laboratories.

As we advance our work in FTD and Crohn's disease, and assuming we show preclinical proof-of-concept, these will become exciting opportunities for us to expand and address larger patient populations, either alone or in partnership. We believe we have truly just begun to explore the potential for HSC gene therapy in diseases such as these and others, and are excited to share more about the preclinical development of these programs later this year.

So to summarize our path forward on slide 22, the next 12 to 18 months offers many important milestones as we continue our evolution to a commercial stage company and advance our next wave of clinical stage therapies. We anticipate approval and launch of OTL-200 for MLD in the EU, additional regulatory filings in Wiskott-Aldrich syndrome and MLD, a new registrational study next year in MPS-I, multiple clinical data readouts from our neurometabolic franchise and further detail and progress on our research programs in FTD and Crohn's disease.

To wrap up our prepared remarks, we are confident that our new strategic plan and operational decisions announced today will set us on the right path to achieve long-term growth, build sustainable value and serve an even larger number of patients who could benefit from hematopoietic stem cell gene therapy.

Thank you very much. And now we'll use the rest of the time to answer your questions. So let's have the operator open up the line.

Operator

Thank you. [Operator Instructions] And our first question comes from Whitney Ijem from Guggenheim. Your line is now open. Please go ahead.

Whitney Ijem -- Guggenheim -- Analyst

Hey guys, thanks for the question. So first, just wondering, can you give us some more color maybe on the discussions you're having with the FDA in MLD? Kind of what are they looking for? And I guess is the IND just sort of a tool to get RMAT? Or is there additional kind of clinical work you plan you think you'll need to do?

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Hi. Whitney, Bobby here. Thanks for that. In general, we can't go into all of the details, obviously, of the discussions with the FDA. But I think in the release and in the script, we've talked about the fact that they've commented on certain endpoints, the natural history, the CMC package, etc. Now I think I'd just like to say this is a and obviously, a very complex disease, a very ultra-rare population, we have extensive data set, and we have already filed with the EMA. Now for historical reasons, there hasn't been an IND in the U.S., and so we haven't had the opportunity to discuss that data in full with the FDA.

What I can say is that we do have an extensive body of data. We want to be able to talk to the FDA and have a comprehensive dialogue to be able to explain that full data set. We feel confident that we have the endpoints that they are looking for and the data that they are asking for. But we need to have that conversation with them in order to be explain to be able to do that fully. So that's why we're filing an IND filing, filing the RMAT, so we can have that dialogue. And once we can clarify those issues, then we can go ahead with submission of the BLA.

Whitney Ijem -- Guggenheim -- Analyst

Okay. Got it. And then just one quick follow-up on MLD. Can you remind us where you are with newborn screening, I guess, both in Europe and then in the U.S.?

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Yes, sure. So newborn screening for MLD, I think, is an important, a very important issue, because, obviously, that means that we'll be able to get earlier diagnosis and have more patients be able to access therapy. So it's a very important part of our kind of diagnostic initiatives in this disease. What we have so far is that we have worked with a key scientist, where an assay has been developed, that's been published to show that there is an assay that we've done on a dry blood spot to understand the decrease in the enzyme activity and also the increase in the sulfur-type levels.

And that assay is now going to be put into pilots, and we are funding a pilot in New York State, and that will start later this year. And we're also looking at pilots in other states as well. We're also transferring that assay to Italy and that and we're funding a program in Tuscany and in Italy where that will be rolled out. And we're also looking for opportunities in other EU states as well. So I'd say, there are already two that are going to start, we are looking to fund other pilots as well.

And together, that data will allow us to validate the assay but also allow wider implementation of newborn screening, and also for nomination, for example, onto the WAS panel for implementation in states in the U.S. So I say there's a lot of work going on in order to make sure that happens.

Whitney Ijem -- Guggenheim -- Analyst

Great, thanks.

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Thank you.

Operator

And your next question comes from Esther Rajavelu from Oppenheimer. Your line is now open. Please go ahead.

Esther Rajavelu -- Oppenheimer -- Analyst

Hey guys. Congrats on all the changes. I guess, my first question again on MLD is I'm trying to understand the duration between EU approval and NBS. I don't know if that math or if that graph was drawn to scale, but it looks like it's almost a four-year lag from first approval to newborn screening. Can you help us understand the time line there?

Frank Thomas -- President and Chief Operating Officer

You mean between EU and U.S. or around newborn screening or both?

Esther Rajavelu -- Oppenheimer -- Analyst

Around newborn screening, generally, between EU approval and newborn screening.

Frank Thomas -- President and Chief Operating Officer

Yes, sure. As Bobby mentioned, there's a pretty active program planned around newborn screening that I think we will expect will come over time in order to even apply for the Ross Panel, there are certain requirements that need to be met in terms of the number of patients or a number of children that have to be screened, identifying the positive patients and then you can apply on the Ross Panel. And then from there, there's a process that you go through in the U.S., at least, on a state-by-state basis to get it added.

So I think there are a number of steps along the way. We haven't guided specifically on the time line, but I think there are other precedents out there that suggest that this could take years. Once we screen the once we apply for the Ross Panel to get sort of full reimbursement, but obviously, we'll focus on states initially after that approval that have the largest populations.

Esther Rajavelu -- Oppenheimer -- Analyst

And my Yes, go ahead.

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Esther for I was just going to say for the EU, obviously, we're looking for approval for MLD later this year. As far as people screening in the EU is concerned, that's on a country-by-country basis, and sometimes it's even certain states. But I've worked on newborn screening for SCID, for example, in the EU. And now there are numerous countries in the EU that are screening for SCID with a number of pilots also in the pipeline as well. And so with that kind of experience, and we would be looking to kind of really facilitate that uptake in the EU and as in and in the U.S., as Frank has already mentioned.

Esther Rajavelu -- Oppenheimer -- Analyst

Understood. And then the decision to defer capex, is that related to some of the time lines for U.S. versus EU approvals and the newborn screening? Or what really kind of went into that delay, given you already have some cost into that facility?

Frank Thomas -- President and Chief Operating Officer

Yes. I can start, and Bobby can add on that again. I think, obviously, we continue to believe in-house manufacturing is an important capability that we're going to want to have over some period of time. It really comes down to sort of when is the need for that capacity and capability relative to the various programs we have. Working with the CDMOs that we have today, we know that we have capacity for the MLD and WAS launches and for a period beyond the launch. So there's not an imminent need to secure the capacity today, and we think that deferring it makes the most sense. We'll continue to work with CDMOs on those launches.

We will look at bringing on a U.S. supplier for drug product to be able to more easily service the U.S. market. And then longer term, look at, potentially, in-house manufacturing at a site and location that we think is more fitted to what the capacity needs will be. So I wouldn't say it's tied to any sort of launch time lines because the plan always was to utilize CDMOs for WAS and MLD. But certainly, as those launches roll out and demand grows, our capacity needs will grow and that will be the appropriate time, we think, to make the investment.

Esther Rajavelu -- Oppenheimer -- Analyst

Understood. Thank you very much.

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Thank you.

Operator

And your next question comes from Anupam Rama from JPMorgan. Your line is now open. Please go ahead.

Tessa Romero -- JPMorgan -- Analyst

Good morning, guys. This is Tessa on the call this morning for Anupam. You pointed out that updated interim data from the proof-of-concept trial for OTL-203 and MPS-I is expected at ASGCT upcoming here next week. Can you remind us of what will be the size and scope of data that we will see at the conference? And maybe can you just clarify if there is any other newly updated clinical data we should be thinking about for other programs at ASGCT?

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Okay, fine. Bobby here, and I'll take this question. On MPS-I, so just to remind you, the proof-of-concept study has enrolled all eight patients, so that's been fully recruited into. What we've shared with you previously is biochemical data showing the overexpression of IDUA activity, the decrease in the heparan and dermatan sulfate, the engraftment of gene-modified cells and some early clinical data on patients who have got beyond the one-year time frame after gene therapy. There was only previously one patient who had reached that time point.

So there's been further follow-up on those eight patients. We'll be able to show you longer-term engraftment of the gene-modified cells, more consistent overexpression of enzymatic activity, longer follow-up, decrease in GAG levels and also more clinical data on patients who have got to longer endpoints as well. So we'll be able to show data assay on clinical data on patients after longer follow-up. And this will be both on their cognitive outcome, but we also will have data on, for example, growth parameters as well, which is again a big issue in MPS-I. So that is for MPS-I.

We will also be sharing data on OTL-101 as well for ADA-SCID. There will be further follow-up on patients who have undergone treatment for transfusion-dependent beta-thalassemia, so longer follow-up on the patients who have been treated so far. So there's really quite, as well as other programs. So there's really quite an extensive body of data, and it just showcases the potential of Orchard's platform across a number of different diseases and how HSC gene therapy can correct the underlying defects in immune deficiencies, neurometabolic deficiencies and hemoglobin opportunities as well. And obviously, we'll give you more detail on those different abstracts next week.

Tessa Romero -- JPMorgan -- Analyst

Great, thank you.

Bobby Gaspar, M.D., Ph.D. -- Chief Executive Officer

Thank you.

Operator

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Orchard Therapeutics (ORTX) Q1 2020 Earnings Call Transcript - Motley Fool