bluebird bio, Inc. (NASDAQ:BLUE) Q4 2023 Earnings Conference Call March 26, 2024 8:00 AM ET

Company Participants

Courtney O'Leary - Director of IR
Andrew Obenshain - CEO
Tom Klima - Chief Commercial and Operating Officer
Chris Krawtschuk - CFO

Conference Call Participants

Jason Gerberry - Bank of America Securities
Danielle Brill - Raymond James
Jack Allen - Baird
Gena Wang - Barclays
Eric Joseph - JPMorgan
Mani Foroohar - Leerink
Jeffrey Hung - Morgan Stanley
Salveen Richter - Goldman Sachs
Sami Corwin - William Blair

Operator

Good day, and welcome to bluebird bio Fourth Quarter and 2023 Annual Results Conference Call.

At this time all participants are in a listen-only mode. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Courtney O'Leary, Investor Relations. Please go ahead.

Courtney O'Leary

Good morning, everyone and thank you for joining our fourth quarter and 2023 annual results call today. My name is Courtney O'Leary, Director of Investor Relations at bluebird bio.

Before we begin, let me review our Safe Harbor statement. Today's discussion contains statements that are forward-looking under the Private Securities Litigation Reform Act of 1995, including expectations regarding our future financial results and financial position, in addition to statements of the company's plans, expectations or intentions regarding regulatory progress, commercialization plans and business operations. Such statements are based on current expectations and assumptions that are subject to risks and uncertainties and involve a number of risk factors that could cause actual results to differ materially from projected results. A description of these risks is contained in our filings with the SEC, which are available on the Investor Relations section of our website, www.bluebirdbio.com.

On today's call, Andrew Obenshain, bluebird bio's CEO, will provide a general corporate update. And then Tom Klima, Chief Commercial and Operating Officer, will discuss progress on the commercial launches of LYFGENIA, ZYNTEGLO and SKYSONA. And finally, Chris Krawtschuk, Chief Financial Officer will provide a financial update before opening the call up for Q&A.

With that, I will turn it over to Andrew.

Andrew Obenshain

Thanks, Courtney and thank you, everyone, for joining our call this morning as we provide an update on our fourth quarter and 2023 annual results and discuss our strategic outlook and planned milestones for 2024.

Earlier this morning, we put out an 8-K announcing that we will be restating financial information for 2022 and for the first three quarters of 2023, and that we've submitted an extension on our 10-K filing. We now anticipate filing the 10-K inclusive of that restatement no later than April 16. Importantly, the restatement does not impact our cash position or revenue. Chris will discuss this in greater detail later in the call.

2023 was a year of significant progress for bluebird. We established ourselves as a commercial gene therapy leader, with a validated commercial strategy that brought both ZYNTEGLO and SKYSONA to patients across the U.S. Our recent commercial progress for LYFGENIA builds on that foundation. With the FDA approval of LYFGENIA for sickle cell disease last December, bluebird is currently the only commercial gene therapy company with three FDA-approved products. Since then, our commercial team has hit the ground running to position ourselves for a strong LYFGENIA launch.

We have talked before about the benefits for our significant commercial head start with ZYNTEGLO. And today, we are seeing the fruits of that labor translate into real momentum for LYFGENIA. We have activated 62 qualified treatment centers and have signed our first outcome space agreement for Medicaid, extending access to LYFGENIA to this critical patient population. And 2024 is off to a fast start, with nine patient starts already this year. Tom will dive deeper into our commercial progress momentarily.

Last week, we also announced that we entered into a five year term loan with Hercules Capital, for up to $175 million. This transaction provides bluebird with an infusion of capital, is expected to extend our cash runway beyond the next 24 months. Last August, on our Q2 earnings call, we set out a five year vision for bluebird as a standalone commercial gene therapy company. We outlined our near-term path to profitability and are expecting additional growth and scale over the next five years. This funding forwards that vision to capitalize on the multibillion dollar opportunity in front of us in the U.S.

I will now hand the call over to Tom to highlight the significant progress happening in our commercial launches.

Tom Klima

Thanks, Andrew and good morning, everyone. As Andrew noted, 2023 was a pivotal year for bluebird, in which we built our commercial foundation with ZYNTEGLO, beta thalassemia and SKYSONA for Cerebral Adrenoleukodystrophy. Today, we are capitalizing on the head start to accelerate the launch of LYFGENIA for sickle cell disease.

As a reminder, our launches are focused on three core elements for success. First, establishing a robust network of qualified treatment centers or QTCs. These are transplant centers with significant experience in cell and gene therapy. As Andrew mentioned, today, we have 62 activated QTCs, unparalleled compared to others in the field. Second, ensuring the value of our therapies are recognized and that patients have timely, equitable access. In a moment, I'll dive deeper into our progress on access and reimbursement.

And lastly, optimizing the patient and provider experience. Gene therapy is a high touch business where transparency, collaboration and understanding the needs of patients, families and providers is paramount. Our deep understanding of the gene therapy process, our dedicated focus and our experience over the last 18 months allow us to be a strong partner to our activated QTCs, as we help them bring life-changing therapies to their patients.

Three months into the LYFGENIA launch, patient demand is strong. I am very excited to share today that we expect our first patient start will be scheduled imminently, and we are extremely encouraged by the number of enrollments and patients preparing for treatment from multiple treatment centers across our QTC network. We anticipate starts for LYFGENIA to grow quarter-over-quarter, with the majority occurring in the second half of the year as momentum builds. We anticipate that the first revenues for LYFGENIA will be reported in Q3.

Moving to ZYNTEGLO, we continue to see strong linear growth with seven patient starts since the beginning of 2024, in addition to the 20 patient starts completed for ZYNTEGLO in 2023. Additionally, we have completed two patient starts for SKYSONA since the beginning of 2024, in addition to the six patient starts completed for SKYSONA last year. And as a reminder, patient starts, which is when cell collection occurs, remains the key commercial metric to watch in the early stages of our launches as this is the value-creating moment for the company, with revenue being recognized when the patient is infused.

For modeling purposes, you can expect that patients are infused one to two quarters following cell collection. And in our experience, once the patient goes through the cell collection, they continue on the treatment journey. To-date, every patient who has started the process has either completed the process or remains in the process. Going forward, we plan to provide quarterly updates on patient starts for each of our therapies as we work towards the 85 to 105 patient starts we guided to in 2024.

Turning to access and reimbursement, gene therapies are onetime transformative treatments and bring tremendous value to the healthcare system and to patients. For years, bluebird has led the way in articulating the value of gene therapies to payers and charting paths to access for patients. We continue to see timely access for ZYNTEGLO and SKYSONA with 0 ultimate denials for either therapy across both Medicaid and commercial payers. Payers are recognizing the value of these therapies in the high burden of disease.

And today, we are seeing the same early success with LYFGENIA, where our goal is timely, equitable access for patients. And our approach is working. We have designed outcomes-based agreements that are unique to LYFGENIA, offering payers meaningful risk-sharing tied to [ VOE-related hospitalizations, with patients typically followed for three years. In addition to a commercial offering, we've designed an offering specifically for Medicaid that addresses the need for predictability and operational ease that is essential for states grappling with resource constraints.

Earlier this month, we announced that bluebird signed its first outcomes-based agreement for LYFGENIA with Michigan's Medicaid program, demonstrating support from government payers for these types of innovative arrangements. We've also signed a total of four commercial outcomes-based agreements for LYFGENIA, covering more than 200 million lives. In three short months, we've already seen close to 90% of coverage policies cover LYFGENIA at parity, including policies from major national insurers, such as Aetna, Anthem and Cigna.

We continue to be focused on access for Medicaid patients in 2024, and discussions are ongoing with more than 15 Medicaid agencies, representing 80% of the individuals with sickle cell disease in the U.S. We are also actively engaged with CMMI on its cell and gene therapy access demonstration that is slated to begin in 2025, which could serve as a bandwidth extender for states who do not have the ability to implement outcomes-based agreements on their own.

Moving to our QTC network, one of the most significant advantages of our commercial head start has been our ability to build our synergistic QTC network. We now have 62 activated centers, the largest network of qualified treatment centers for hemoglobinopathies, 49 of which are already ready to receive referrals for LYFGENIA today. This means that approximately 95% of people living with sickle cell disease are within 200 miles or less of a bluebird QTC.

We anticipate additional QTC expansion across our portfolio in 2024. We also recently signed agreements with QTCs in geographies with important proximity to sickle cell patients, where we are meeting patients where they are, in Georgia, across Florida and throughout the New York Metropolitan area. Additionally five centers have also been activated to administer SKYSONA for patients with CALD. We were able to quickly activate our LYFGENIA QTC due to both bluebird [ph] experience of setting up these centers for ZYNTEGLO and the strong relationships we have built with these centers throughout 2023.

From onboarding through infusion, our QTCs are comfortable with our process and have grown to expect the transparency and the partnership that bluebird brings to the table.

To recap, ZYNTEGLO and SKYSONA launches continue to progress as planned, and we anticipate strong linear growth from ZYNTEGLO in 2024. We've made incredible early progress in our LYFGENIA launch, building on our validated commercial platform. We are seeing clear demand from patients and physicians, payers are recognizing the value of LYFGENIA in providing access and our QTC network is fully ready to help patients start their journey with a curative therapy.

And now I'd like to turn the call over to Chris.

Chris Krawtschuk

Thanks, Tom, and good morning, everyone. Before discussing the details of the restatement and the filing extension we announced this morning, I want to highlight the financial results we reported in our press release.

In the fourth quarter, we reported $7.8 million in total revenue, primarily driven from product revenue from ZYNTEGLO and SKYSONA. As a reminder, we recognize revenue upon infusion of the drug product. Additional drug product for several patients were delivered at the end of December and infused in January. So this revenue will be recognized in the first quarter of 2024.

For the full year 2023, we reported $29.5 million in net revenue, with $16.7 million of revenue attributable to ZYNTEGLO and $12.4 million of revenue attributable to SKYSONA, with cumulative gross to net discounts across the portfolio of 2 products of approximately 19%. In 2024, we anticipate gross to net discounts in the range of 20% to 25%, with fluctuations based on product and payer mix as well as utilization of our outcomes-based agreements.

Going forward, bluebird plans to provide revenue by product on a quarterly basis, and as Tom shared earlier, we expect the first LYFGENIA patient infusion and revenue recognition in the third quarter of 2024.

We ended the year with cash and cash equivalents, marketable securities and restricted cash of approximately $275 million, which includes $53 million of restricted cash. We're very pleased to announce that we entered into the five year term loan with Hercules Capital for $175 million. This financing provides an infusion of non-diluted capital for bluebird, helping fuel the launch of LYFGENIA and deliver on our mission as a company.

The loan provides for up to $175 million in the aggregate, and it's available in four tranches. The first tranche in the amount of $75 million was drawn on closing. We may draw additional two tranches over the next 18 months in aggregate, of an amount up to $50 million, and this is subject to the achievement of commercial milestones tied to LYFGENIA patient starts and gross profit. The fourth tranche of up to $50 million may be available at the sole discretion of Hercules.

Importantly, and to reiterate Andrew's comments, based on our launch estimates and our current business plans and assuming the first three launches are executed, the transaction is expected to extend our cash runway beyond the next 24 months and puts us in a durable capital position as we approach profitability.

Lastly, this morning, we announced we will restate financial information for the full year of 2022 and for the first three quarters of both 2022 and 2023. The restatement relates to the application of our accounting policies for contracts with our contract manufacturing organizations and suppliers, which did not consistently combine lease and non-lease components, and was discovered by our internal finance team during the preparation of our annual financial statements.

For 2022, we estimate the understatement of lease assets and lease liabilities of approximately $100 million to $200 million for the full year, as well as an estimated understatement of lease assets and liabilities of approximately $30 million to $125 million for the first 3 quarters of 2022 and 2023. While we're still working through the exact details, the lease will be reclassified as finance leases as a result, and we anticipate the increase of noncash interest expense on our P&L.

The restatement is not expected to have any impact on our cash position or revenue. In consideration of the time we will take to complete the restatement, we have filed for an extension of our 10-K, and we anticipate that our 2023 10-K inclusive of the restated periods will be filed April 16.

And with that, let me turn it back over to Andrew.

Andrew Obenshain

Thank you, Chris. And to summarize, bluebird is deploying a validated commercial gene therapy strategy with three FDA-approved therapies taking place in 2024, delivering on our promise to patients and their families. We expect 2024 to be a transformative year for our company, and we look forward to providing more updates in the upcoming quarters as our commercial launch of LYFGENIA progresses.

And with that, I'd like to open it up for questions. Operator?

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Our first question will come from the line of Jason Gerberry with Bank of America. Your line is now open.

Jason Gerberry

Hi, guys. Thanks for taking my questions. I was wondering maybe if you can just speak to, in the fourth quarter, the quarterly step down in revenue and what you're seeing there, to what extent that maybe speaks to sort of the conversion dynamics of these starts to an actual revenue recognition event. And then can you comment at all -- just as a follow-up -- just directionally, the flow of new starts first half versus second half and your outlook for the full year? Thanks.

Andrew Obenshain

Yes, good morning, Jason. Thanks for the question. I might just ask Tom, just talk a little bit about the patient dynamics and how they're coming in and the flow, both for the fourth quarter with ZYNTEGLO and then for the first and the second half of this year with LYFGENIA. Go ahead, Tom.

Tom Klima

Yes, good morning, Jason. Thanks for the question. So we saw strong demand and building demand over the course of the year last year for both for ZYNTEGLO and then as we expected, we started six patients for SKYSONA. With ZYNTEGLO, we actually collected a number of patients at the end of the year that elected to be treated after the start of the New Year. So although the collections were on track in Q4, many of those patients went on to be infused in Q1.

So that was the reason you saw a little bit of a dip in Q4. But we remain very positive on patient demand for ZYNTEGLO. We also are seeing just very strong demand for us for LYFGENIA. We expect a linear build over the course of this year with the vast majority of the LYFGENIA starts happening in the second half of the year.

Andrew Obenshain

And Jason, just to reiterate what we said earlier too, we had some drug products that were delivered to the QTCs in Q4, but actually were not infused and those infusions will happen in Q1 and be recognized there. I would also say that to -- quarter-to-date, where we've had our best and strongest quarter to date on starts, nine total.

Jason Gerberry

Got it. Thanks.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Danielle Brill with Raymond James. Your line is now open.

Danielle Brill

Hi, guys. Good morning. Thank you so much for the question. I guess as a follow-up to Jason's, do you still expect LYFGENIA can make up over 50% of the total volume this year? And then I know you said that the first patient start is imminent, but I believe in the past, you've communicated that multiple patients would start in 1Q. Just curious what's gaiting getting those patients started? Thank you.

Andrew Obenshain

Right. I'll ask Tom to answer that. Go ahead, Tom.

Tom Klima

Yes. So again, we're excited about the momentum and the demand we're seeing with LYFGENIA. We do expect roughly half or more of the volume to come from LYFGENIA. Obviously, it's a much larger patient population, and we should see a lot of the starts starting to pick up in the second half of the year as we build momentum. We did say that we would have a patient start in Q1. We believe that we'll have our first patient started very soon, imminently. We've seen again, very strong demand. And what we've seen so far is a number of patients who have been enrolled in the process and who are going through the process of getting ready for treatment across a number of different QTCs. And keep in mind that if you look at—I'll just refer you to the package insert for LYFGENIA. It takes about 2 months on average for patients to be medically ready as they have to wash out their hydroxyurea or disease-modifying therapies they might be on for at least two months. They have to also go through two rounds of transfusions, one month each. So it just takes patients a little longer to get ready for therapy.

Danielle Brill

Got it. Thanks very much.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Jack Allen with Baird. Your line is now open.

Jack Allen

Hey, thanks for taking the question. I wanted to ask about your manufacturing capacity and how you think about potential influx in patients in the quarters and potentially the second half as well. Can you just provide some color as it relates to what capacity you have? And how could you meet demand as it comes in, in different kind of waves as we think about the second half being really the build here as it relates to LYFGENIA?

Andrew Obenshain

Good morning, Jack. I'll take that one. So the -- first of all, I think important to understand is that the supply chain for ZYNTEGLO or SKYSONA is one supply chain, and there's the supply chain for LYFGENIA. So the two don't impede upon each other. And the way we've designed—and obviously we've designed our capacity for LYFGENIA to be larger than our capacity for ZYNTEGLO and SKYSONA, in anticipation of a larger demand there. And we do on both sides, both the sector and with drug product, we do anticipate that we have the volume or the capacity to meet the initial launch expectations. And what we also have in place is plans to expand that capacity as we see demand coming in.

So we do anticipate that we do have capacity for this year in the launch phase of all of our products.

Jack Allen

Got it. Thanks.

Operator

Thank you. Our next question comes from the line of Gena Wang with Barclays. Gena, your line is now open.

Gena Wang

I wanted to know that now you have a little bit early real-world experience, what is your expected from start to finish for LYFGENIA?

Andrew Obenshain

Good morning, Gena. Tom, go ahead.

Tom Klima

Yeah, good morning, Gena. So what we're saying is that, obviously, from cell collection to infusion one to two quarters. And the biggest part of that time is just the manufacturing time and the range in the packaging service between 70 and 105 days plus two weeks. So that's the vast majority of the time. And then we obviously ship it back to QTC and then it's up to the QTC when they infuse it. So we're saying for modeling purposes, one to two quarters.

Gena Wang

Thank you.

Operator

Thank you. Our next question comes from the line of Eric Joseph with JPMorgan. Your line is now open.

Eric Joseph

Hi, good morning. Thanks for taking the question. I guess just -- if we're looking back at 2023, can you just provide a little more color on how many of the '24, I think total cell collections contributed to revenue generation and whether there -- yes, explicitly, how many patients actually contributed to revenue recognition? And then how average time to treatment between collection and treatment has trended? What avenues do you anticipate there being to sort of improve conversion rates going forward? Thank you.

Andrew Obenshain

So Eric good morning. So with 26 collections in 2023, every single patient that has gone through the process is still in the process. They've either been infused or had the drug product delivered or the product is in process. They're all still in the process. And we haven't actually given numbers of infusions. So I'm not going to send directly. But we said we have -- we infused the number in 2023. And we have some products always delivered in Q4, but not infused and you'll see that revenue in Q1 as patients will be infused early this year.

In general, you're going to see that the time from collection to infusion is one to two quarters. There will be some outliers there just as the hospitals use [indiscernible] or something else happens, but in general, it's 1 to 2 quarters. As we get more collections and as we get more data, we want to be able to narrow that number down for you and give you a kind of a more precise number, but still we're still dealing with relatively small numbers.

Eric Joseph

Okay. And to remain in process, I guess is there, a bracket time frame, I guess, how long can a patient kind of be in process? Is there ultimately a 9, 12 month window?

Andrew Obenshain

So there's really no end date for them being in the process except for the expiration of the drug products. It's just about a year, right, once you manufactured it that the drug product would expire after a year or a little bit longer. So that would be in process. We don't anticipate anyone going that far. But again, remember, this is an election that the patient makes to get treated, so very often they will schedule it in around life events, et cetera. That's why it's somewhat unpredictable once we deliver the product back to the hospital, when they will get infused.

Eric Joseph

Okay, thanks for taking question.

Operator

Our next question comes from the line of Mani Foroohar with Leerink Partners. Your line is now open.

Mani Foroohar

I want to pivot a little bit to thinking about broader market dynamics. You've obviously talked about finding patient demand, volume demand out there for LYFGENIA, you said that, that's going to be perhaps half or more of the 85 to 105 patients. Can you give us a little bit of sense of how deep that backlog is? How much clarity do you have into it? I know you can't give us a numerical guidance number of number of patients currently, but can you give us some -- can you put some color around exactly what that backlog have identified if any potential of LYFGENIA patients looks like?

And I guess a separate follow-up, can you give us a sense of exactly what demand metrics and other data was available to Hercules as part of your engagement with them prior to your transaction with them? Just trying to understand their due diligence process as well.

Andrew Obenshain

Yes. So I'm just going to pass it to Tom as to talk about the backlog or the interest in LYFGENIA. Chris, will talk about just what we've provided Hercules. Go ahead, Tom.

Tom Klima

Yes. Good morning, Mani. Keep in mind that if you look back a year, people were asking questions around could we get to our goal of 40 to 50 QTCs, which was factor in making sure that patients had access to therapy. People are also asking questions around reimbursement. And then lastly, people were asking about patient demand. Now we have 62 qualified treatment centers up and running. We've seen reimbursement happen. We have positive coverage policy so far with LYFGENIA.

So that box is being checked. And now you're looking at patient demand. And we've seen historically in market research, that over 70% of patients who have more severe sickle cell disease, have said they would seek a gene therapy if recommended by their physician. And now we're seeing that play out in real life, we have multiple enrollments already just in a few months after approval across multiple QTCs.

We wouldn't expect a huge bolus because patients, as Andrew mentioned, can treat, get treated per their schedules. And also I think QTCs are going to want to treat a handful of patients first before they go through their listed patients. But anecdotally, we've heard of long wait list at QTCs of patients who have sickle cell disease that are looking to be treated.

So we're -- again, I can't overemphasize how excited we are about the early demand that we're seeing.

Andrew Obenshain

Chris, do you want to comment on what we have provided Hercules?

Chris Krawtschuk

Thanks for the question. With respect to what Hercules has received, so Hercules received customary information as it relates to projections not just 2024, but beyond that. And the confidence that having a third party come in and scrutinize our projection should provide confidence to the marketplace on the achievability of those considering they entered into the arrangement for the $175 million finance. What I would say though is that the patient start guidance that you saw there for LYFGENIA should not be viewed as consensus, right? That's viewed as progress.

So that milestone associated with that is not consensus. We provided our guidance, which is the 85 to 105 starts.

Mani Foroohar

Okay, thanks helpful. Thanks guys.

Operator

Thank you. One moment for our next question please. Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is now open.

Jeffrey Hung

Thanks for taking my questions. For LYFGENIA, with 49 QTCs already receiving referrals, what proportion of these sites might have their first patient cell collections in the first half of the year? And what are the gaiting factors that might result in different time lines, particularly for the 35 sites that were online at the beginning of the year? And then I have a follow-up.

Andrew Obenshain

Go ahead, Tom.

Tom Klima

Yes, sure. Yes, we haven't really given specific guidance per QTC, but needless to say, a lot of QTCs were coming on board late last year in anticipation for LYFGENIA launch and approval. So we would expect most of our QTCs to be pretty excited about getting patients started on LYFGENIA. In most cases, they are waiting for patients to come in for their regular appointments. And in some cases, if they have a waiting list, say for a patient that wanted to try a gene therapy through a clinical trial, then those patients might go faster.

So really, the dynamic will play out, but we're excited about the early enrollments that we've seen and across multiple QTCs, not just one or two QTCs, and we're excited about the excitement for gene therapy.

Jeffrey Hung

Okay. Thanks. And then for the third tranche of the term loan facility, what would you need to see in patient starts by the end of the year to be on track to reach the $30 million gross profit milestone by the end of the first half of '25? Thanks.

Andrew Obenshain

Go ahead, Chris.

Chris Krawtschuk

So we're not going to -- we haven't commented on that. What we commented on was the exact metric associated with that. But we're not going to comment on the patient start number. Remember, our patient start guidance that we provided and the second tranche was the 35 by September, the 55 by the end of the year for LYFGENIA. And then there's a gross profit metric also. And then for the third tranche -- but we're not going to provide that level of detail associated with the number of equivalent patient starts to get to the gross profit.

Andrew Obenshain

Sorry, Jeff, you were asking about the first -- you said the third tranche, I think you meant the second tranche?

Jeffrey Hung

Yes. I was talking about the third tranche. Yes.

Andrew Obenshain

So the first tranche of $50 million, second tranche of $25 million, which is -- it's keyed off of either the 35 or the 55 starts by the end of the year. And then there's a third tranche to '25 that is fed off of a different metric which is gross profit.

Chris Krawtschuk

Yes. And just to be clear, the first tranche was the 75, the second tranche is the 25. 25 is attributable to the LYFGENIA patient starts, as I said, 35 by September, 55 by December 31. And then the third tranche is associated with gross profit. And then, of course, the fourth tranche is the 50 that is at the discretion of Hercules.

Jeffrey Hung

Yes, thank you. Yeah, you guys -- you said that you wouldn't comment on the number of patient starts for the $30 million gross profit. Yeah, okay, thank you.

Andrew Obenshain

That's correct.

Chris Krawtschuk

That's correct.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Salveen Richter

Good morning. Thanks for taking my questions. Just in line with the trajectory that you're seeing right now and the understanding of the various onboarding dynamics, reimbursement dynamics, how are you thinking about the peak opportunity here for the drug? And just maybe an update on for ex-U.S. commercialization. Thank you.

Andrew Obenshain

Yes. So Salveen, it was little hard to hear, but I think you asked what the peak opportunity is for the drug?

Salveen Richter

Yes. And ex U.S. commercialization outlook.

Andrew Obenshain

Okay, got it. So let me take that. So we do see this as a multibillion-dollar opportunity at peak in the U.S. alone. Ex-U.S., we do think there's a very attractive opportunity there as well. Right now, we, as a company, are focused exclusively on the U.S. If we go ex-U.S., we most certainly do that with a partner. We are watching very closely the reimbursement dynamics of gene therapy in Europe as well. That's kind of a key dynamic that will determine the opportunity there.

Salveen Richter

Thank you.

Operator

Thank you. One moment for our next question please. Our next question comes from the line of Sami Corwin with William Blair. Your line is now open.

Sami Corwin

Hi, there. Thanks for taking my questions. I was curious if you could speak a little more as to the cost of goods in your gross margins and how you expect them to change as our launches across the portfolio continue. And then can you provide any granularity in terms of your assumptions for the LYFGENIA launch this year and the percentage of patients you expect to be covered or covered by Medicaid versus private insurers?

Andrew Obenshain

Yes, sure. Good morning. So let me have Tom take the second part first, and then I'll go to Chris with the percentage of LYFGENIA in Medicaid.

Tom Klima

Yes. Just to give you the stats again, about 50% of patients or people living with sickle cell disease are covered by Medicaid, about 45% are covered by commercial insurance and then a small portion of Medicare. It's hard to predict who the early patients will be, but we would expect over time that the payer mix will play out like we've seen historically.

Chris Krawtschuk

And then just covering on the cost of sales and maybe I'll answer it a slightly different way, which I think is what you're intending, is the gross margin. So the gross margin for the company will improve as we scale, and we've said that we would get to a 70% gross margin. And as we scale the company, not only with filling the capacity with infusions, and then continuing to kind of scale the capacity in a gated fashion over time as needed. The gross margin will continue to improve to achieve that 70% that we discussed.

Sami Corwin

Great, thanks.

Operator

Thank you. One moment for our next question, please. Our next question comes from the line of Yanan Zhu [ph] with Wells Fargo. Your line is now open.

Unidentified Analyst

Hi, thanks for taking our questions. So just curious, when you say multiple patients enrolled for LYFGENIA, does enrollment imply approval of insurance. And the time from enrollment to cell collection is the main gaiting factor those washout period and also the pre-transfusions? If not what might be the gaiting factor you see. Also as a quick follow-up, if you can talk about the 19% gross to net to date, is that different significantly between ZYNTEGLO and SKYSONA, and any expectation for the gross to net for LYFGENIA to be very different from that 19% number? Thanks.

Andrew Obenshain

Thanks for the question. Tom, why don't you address the enrollments, and then we'll have Chris address the gross to net question.

Tom Klima

Yes. Again, we're very excited about the multiple enrollments across multiple QTCs. I think it's an indicator of strong demand. The road to yes, [ph] as we call it, is multifaceted, and the two big components there are, obviously, as you mentioned, making sure that they're covered by their insurance and that's taking approximately what it did with ZYNTEGLO. We're seeing, on average, about two weeks. And the second part of being ready is being medically ready, and this is a little bit different with LYFGENIA than it was for ZYNTEGLO.

With LYFGENIA there's a washout period of the other medications. For example, hydroxyurea has to be discontinued for at least two months before they start therapy, and they're also supposed to go for transfusions, at least two transfusions one month apart. So once they're enrolled and once they're going through the process, if they're not already doing transfusions, I mean if they're already doing transfusions and they're not on one of the medications that needs to be discontinued, they can go a lot faster.

So I'm a little hesitant to give you an average right now because it's just going to depend on the patients. And we provided enrollments today. Enrollment is an early indicator of patient demand the thing to watch going forward is the number of patient starts. That continues to be the value-creating moment for the company.

Andrew Obenshain

And then, Chris, do you want to comment on gross to net?

Chris Krawtschuk

So the 19% that we discussed between the combined two products, just characteristically, the difference between ZYNTEGLO and SKYSONA, ZYNTEGLO has an outcomes-based agreement, SKYSONA does not. And then what to expect on a go-forward basis as LYFGENIA comes into the fray is a higher increased Medicaid population associated with LYFGENIA. And that's where you saw that we provided guidance to 20% to 25% associated with the combined gross to net population of all three products.

Unidentified Analyst

Got it. Thanks.

Operator

Thank you. One moment for our next question please. Our next question comes from the line of Luca Issi with RBC Capital Markets. Your line is now open.

Unidentified Analyst

This is Renon [ph] for Luca Issi. Thanks for taking my questions. I just wanted to ask, during the last [indiscernible] call after not receiving the PRV, you mentioned that you'll engage in discussion with the agency and attempt to achieve a potentially positive outcome like ultimately, meaning receiving the PRV. Just wondering if there was any update on that.

Andrew Obenshain

Yes. Thanks for the question. We have submitted a request for reconsideration and we are in discussions with the agency. We're not going to elaborate on ongoing discussions with the agency now, but we believe we have a clear and compelling rationale for why LYFGENIA to be awarded a PRV. We'll provide an update when we conclude our discussions.

Unidentified Analyst

Perfect. Thanks for taking my questions.

Operator

Thank you. This will now conclude today's question-and-answer session. I'll now turn the call back over to Andrew Obenshain for closing remarks.

Andrew Obenshain

Great. Thank you, everyone for joining our call this morning and for your questions. Our management team is available for a follow-up call today, and please reach out to Courtney if you would like to connect. Thank you very much.

Operator

This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.