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GBT Global Blood Therapeutics

Participants
Steven Immergut SVP, Head of Corporate Communications and IR
Dr. Ted Love President and Chief Executive Officer
Jeff Farrow Chief Financial Officer
David Johnson Chief Commercial Officer
Dr. Kim Smith Whitley EVP and Head of R&D
Alethia Young Cantor Fitzgerald
Akash Tewari Wolfe Research
Lyla Youssef Cowen & Company
Xinyue Lu RBC Capital Markets
Jason Gerberry Bank of America
Andreas Argyrides Wedbush Securities
Danielle Brill Raymond James
Yanan Zhu Wells Fargo
Paul Choi Goldman Sachs
Yatin Suneja Guggenheim Partners
Matthew Harrison Morgan Stanley
Joon So Lee Truist Securities
Samantha Corwin William Blair
Call transcript
Operator

Greetings, and welcome to the Global Blood Therapeutics Conference Call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow prepared remarks. [Operator instructions] As a reminder, this conference is being recorded. I would now like to turn the call over to Steven Immergut. Please go ahead.

Steven Immergut

Thank you, and welcome to GBT's conference call to discuss the Company's financial results for the first quarter of 2021 and to provide a business update. I'm Steven Immergut, Head of Communications and Investor Relations.

Joining me on the call are Dr. Ted Love, our President and CEO, who will provide an update on our progress in the first quarter; Jeff Farrow, our Chief Financial Officer, we'll review our financial results; David Johnson, or DJ, our Chief Commercial Officer, will give an update on the Oxbryta launch. Ted will then introduce Dr. Kim Smith Whitley, who joined GBT this week as Executive Vice President and Head of R&D. Kim will provide a view on the current environment for sickle cell patient care. Ted will then close with an update on our pipeline and efforts to expand access to Oxbryta. Earlier this afternoon, we issued a press release announcing GBT's business progress and financial results for the first quarter ended March 31, 2021.

Before we begin, I would like to remind you that certain statements we make on this call that are not historical facts may be forward-looking statements that are subject to risks and uncertainties. Information concerning factors that could actual results to differ materially from those expressed or implied by such forward-looking statements are contained in our SEC filings, including, but not limited to, our most recent quarterly report on Form 10-Q as well as in today's press release. Copies of our SEC filings and press releases can be obtained from the Investors page of our company website at gbt.com.

Forward-looking statements made on this call are only as of the time they are made, and you should not place undue reliance on such statements, future events or simply the passage of time may cause our beliefs to change and we disclaim any obligation to update any forward-looking statements other than as required by law. With that, I'll turn the call over to Ted.

Dr. Ted Love

Thank you, Steven, and good afternoon, everyone. In the first quarter, we continued to make progress on our mission to discover, develop and deliver life-changing treatments for people with sickle cell disease. The fundamentals of the Oxbryta launch remained strong.

We continue to see patients benefiting from Oxbryta and increasing real-world experience from health care professionals. I'd like to start by highlighting a real-world evident study presented just two weeks ago at the Annual Meeting of the American Society of Pediatric Hematology Oncology. Dr. Allen Anderson and colleagues from Greenville, South Carolina, presented data on 76 Oxbryta patients aged 12 to 70.

For these patients, on average, hemoglobin increased by 2 grams per deciliter, reticulocyte percent decreased from 11.6% to 6.5%, and total bilirubin decreased by 1.4 milligrams per deciliter. These results are consistent with and exceed the clinically important benefit seen in the HOPE Study. Adverse events were rare. Two patients had diarrhea and one patient had a rash, and all were resolved with dose modification. The real-world evidence is consistent with what we've been hearing from many HCPs and adds to our confidence in the long-term potential of Oxbryta.

However, as we expected, the COVID-19 pandemic continues to disrupt the daily lives of sickle cell patients and limit their access to health care. Sickle cell patients continue to have fewer visits to their physicians and fewer hospital admissions compared to pre pandemic.

In addition, while we are optimistic that the availability of vaccines will improve the environment for sickle cell patients, this will take time. Initial data indicates that the majority of patients are wary of being vaccinated in the early phase of the rollout.

All of this is important because the greatest impact to the Oxbryta launch has been the lack of growth of new prescriptions due to COVID. GBT's product sales, like many companies in our industry, were impacted by the increasing infection rate during the first quarter. We had approximately 950 new prescriptions in the quarter, consistent with the expectation we provided.

Let me make an important point.

While changes such as inventory levels and gross can impact revenues, we recognize in the early stage, we are pleased to see the net number of patients on Oxbryta increasing quarter-over-quarter. We feel there is light at the end of the tunnel.

As we all know, every day, more people in the United States are being vaccinated, making progress toward herd immunity.

For those with sickle cell disease, we believe that with time, sentiment toward the vaccine will improve. Based on these trends and the momentum our commercial team is building with patients and HCPS, we continue to believe we will see accelerated growth when sickle cell patients are more comfortable reengaging in person with the health care system, which we think should begin to happen in the second half of 2021.

Our focus on supporting sickle cell patients, educating patients and physicians on Oxbryta and developing our innovative pipeline of potential treatment options is stronger than ever. With that, I will turn the call over to Jeff to provide an update on our first quarter results.

Jeff Farrow

Thank you, Ted. Total net revenue from sales of Oxbryta was $39 million for the first quarter of 2021, an increase of $24.9 million or 177% year-over-year.

As a reminder, GBT recognizes revenue in the U.S. when Oxbryta is received by our specialty distributor or specialty pharmacy partners.

First quarter revenue came in below our expectations, due in part to more of the new patient scripts coming in towards the latter part of the quarter, driven by the higher COVID-19 infection rates in the first two months of the quarter. On a sequential basis, first quarter revenue decreased by 5% from the fourth quarter. There were two other key factors that impacted the sequential comparison.

First, inventory, in the first quarter, our distributors drew down inventory that was built up in the third and fourth quarters of 2020. At the end of the first quarter, days on hand at our distributors, was approximately four days lower than at year-end.

Second, gross to net. In the first quarter, as expected, gross to net increased incrementally to 15% compared to 12% in the fourth quarter. The increase was driven by shifts in payer mix and increased patient co-pay support as commercial insurance out-of-pocket deductibles was reset for patients. Also, as a reminder, gross to net in the fourth quarter of 2020 included a $600,000 return reserve benefit. Net effect of these items more than offset growth of the number of patients taking Oxbryta, which as Ted mentioned, has increased every quarter since launch, despite flat enrollments over the past couple of quarters and potentially in the second quarter of 2021. In previous quarters, we have not given specific revenue guidance; however, as pandemic continues to evolve and have an impact, we want to be clear about our expectations for the second quarter.

For the second quarter, we anticipate modest sequential revenue growth in the 10% to 15% range compared to the first quarter.

Now turning to expenses, cost of sales for the first quarter was $584,000 as compared to $135,000 for the first quarter of 2020 and consistent on a gross margin basis year-over-year. Cost of sales was low in both years as the majority of the manufacturing costs related to Oxbryta sales were incurred prior to FDA approval and thus were recorded as R&D expense.

We continue to expect that the cost of Oxbryta sales as a percentage of revenue will increase its fully expensed product manufactured prior to the FDA approval is completely utilized, which we anticipate will occur during the first half of 2022. R&D expense for the first quarter of 2021 was $51 million compared with $40 million for the same period in 2020. The increase in R&D expense in the first quarter was primarily due to costs related to our preclinical programs, including the upfront expense related to the Sanofi end license.

Our continued research collaboration with pharmaceuticals and an advancement of our inclacumab program, we anticipate a sequential increase in R&D expense in the second quarter as we continue to advance our plan to initiate 2 Phase III studies for inclacumab later this year, which will trigger a $5 million milestone payment by GBT.

We also expect incremental increases in R&D expense in both the third and fourth quarter of 2021, driven by the inclacumab program as well as the advancement of 601 studies and our other expected pipeline-related activities. SG&A for the first quarter of 2021 was $59 million compared with $48 million for the same period in 2020. The increase in SG&A expense was primarily due to increased employee-related costs, including noncash stock compensation and other professional and consulting services associated with the commercialization efforts for Oxbryta, including increased spending on marketing materials. We anticipate a sequential increase in SG&A expense in the second quarter, as we continue to ramp up the rollout of new materials to support Oxbryta. We further expect to see a step-wise increase in SG&A expense in the second half 2021 driven by the rollout of Oxbryta materials, our measured expansion into Europe and the initiation of multiple investigator-sponsored studies. Net loss for the first quarter was $75 million compared to $73 million for the same period in 2020. Basic and diluted net loss per share for the first quarter was $1.21 per share compared with $1.20 per share for the same period in 2020. We ended the quarter with a continued strong balance sheet and with cash, cash equivalents and marketable securities of $482 million compared with $561 million at December 31, 2020.

We continue to believe that we are operating from a position of strength, with a significant opportunity for growth in the future. And with that, I will now turn the call over to DJ.

David Johnson

Thank you, Jeff, and good afternoon, everyone. The commercial team kicked off 2021 with continued progress despite the impact of the ongoing pandemic.

As I have done in prior quarters, I will provide an update around the three key metrics, combined with net revenues, will give you further insight into our progress. These metrics are: new prescriptions for Oxbryta, which informs underlying patient demand; the number of health care providers prescribing Oxbryta, which captures the progress we are making in adoption; and payer coverage, which speaks to the access environment for Oxbryta.

First, new prescriptions.

Our approximately 950 new prescriptions for Oxbryta during the quarter, was in line with our expectations and reflects the ongoing headwind of the pandemic.

Here are some data points that demonstrate the current environment.

First, as Ted mentioned, vaccine hesitancy is a real issue in the sickle cell disease community. In the first quarter, we conducted a survey of more than 120 sickle cell patients, and the results indicate that about 1/3 are waiting potentially much longer to be vaccinated, and an additional 1/4 have no current plans to get vaccinated.

We are actively educating and helping others to educate the sickle cell community around vaccine confidence.

Second, while the use of telemedicine has been helpful for the routine monitoring of our patients, our research shows that health care providers, in general, are less comfortable making treatment decisions such as starting a new therapy via telemedicine. And third, looking across the industry, new-to-brand prescriptions were down about 10% to 20% year-over-year in the fourth and the first quarters. Despite this environment, our commercial team has been building momentum to increase demand as we come out of the pandemic. In the second quarter, we expect flat to modest sequential growth in new prescriptions, and we continue to anticipate more significant growth in new prescriptions once the pandemic subsides.

Our efforts are focused on educating health care providers and patients on Oxbryta and providing support to help patients start and stay on therapy. In order to drive demand for Oxbryta, our field teams are actively highlighting the long-term 72-week analysis of the Phase III HOPE study, which was presented at ASH in December and published in the Lancet Hematology last month. And in line with our plans, we stepped up our digital campaigns, which are efficiently reaching our target audiences. In the first quarter, there was a 30% increase in the visits to oxbryta.com and our Sickle Cell Speaks Disease Awareness Campaign had 111% increase in website visits and has more than 62,500 followers on Facebook, higher than any other SED page.

We are seeing a positive impact from these campaigns.

For patients that viewed our digital advertising in the first quarter, more than 3,300 patients visited a hematologist within one month after seeing an ad.

Turning to adherence, which includes both compliance and persistence, Oxbryta trends continue to be well within the range of our analogs.

In addition, we continue to focus on ways to increase adherence, including by recently launching new get started guides and brochures that support patients' discussions on Oxbryta.

We also introduced new patient kits for those starting therapy, which includes treatment journals, side effect management tip sheets, smart bottle cap stickers, a smartphone app and alarms.

In addition, we transitioned GBT source solutions to a 100% high-touch model, resulting in better conversion and adherence rates. Data from our experience in supporting patients has been submitted to the foundation for sickle cell disease research conference to be held later this month. To complement this, in February, we launched our gbtsource.com website, which provides information about starting and staying on Oxbryta.

We continue to learn and invest in patient support and are motivated by the high levels of satisfaction reported in our patient and health care provider surveys. In order to extend the benefits of GBT source and our support tools to as many patients as possible, we are working with our specialty pharmacy partners to provide key services during their interactions with sickle cell patients on Oxbryta so that patients have multiple avenues to receive the support that they deserve. Overall, we believe these initiatives will continue to build awareness with patients as well as support more physicians prescribing Oxbryta, while also helping them keep their patients on therapy.

Our market research also continues to support the strong fundamentals of Oxbryta.

For example, when we ask Oxbryta patients about their experience, a high majority believe it is easy to take, works well and increases hemoglobin.

Looking at the profile of Oxbryta patient, we continue to see a broad range of baseline hemoglobin and VOC burden among our patients from claims and lab data covering over 2,500 patients. Encouragingly, 50% of the Oxbryta patients have baseline hemoglobin levels greater than 8 grams per deciliter, suggesting that health care providers are increasingly recognizing the importance of addressing polymerization and long-term health, which leads me to my second metric, health care provider penetration.

As we entered the first quarter in person interactions with health care providers by patients and our field team continue to be limited by the increase in new COVID-19 cases.

As we progressed into March, the environment gradually improved, and we had a 15% increase in overall field engagements compared to the several months prior, mainly driven by improved in-person access to health care providers.

During the first quarter, we also completed more speaker programs than any quarter since launch.

Our field teams have been actively engaging with existing and potential new prescribers to highlight our new data and educational support materials. The engagement and feedback on this activity has been encouraging. We added about 170 new prescribers in the first quarter, bringing our total prescribers to around 1,550 since launch. When we look at the breakdown of riders, we continue to see prescriptions being written by both specialists and non-specialists, which we believe is a positive trend for the long-term trajectory of the launch and there continues to be tremendous opportunity to go deeper with these riders and to develop new writers from our large target list.

Turning to the payer coverage.

As we previously reported, in 2020, we achieved broad coverage with 90% of covered lives in the United States.

Our focus is now on working to optimize coverage, and we recently received great news from Texas, a state with one of the largest sickle cell disease patient populations that they voted to add Oxbryta to their preferred drug list going forward. On a related note, we are also sharing data supporting the potential clinical and economic value of Oxbryta and raising hemoglobin levels. In April, a poster presented by Dr. Bill at the Academy of Managed Care Pharmacy Meeting highlighted a large-scale longitudinal analysis, demonstrating that increased hemoglobin levels significantly reduced the risk of end-organ damage for sickle cell patients. In summary, we are well positioned to drive and support incremental growth as more sickle cell patients begin to reengage with their physicians in person, aligned with our ongoing confidence in the long-term potential of Oxbryta. I will now turn the call back over to Ted.

Dr. Ted Love

Thank you, DJ. It's exciting to hear about all the new materials, campaigns and initiatives we are deploying in the field.

Before I get through our pipeline, I'm pleased to bring in the newest member of GBG's leadership team, Dr. Kim Smith Witley. Kim is on Day three at GBT, and she joined the call to say a few words. Kim?

Dr. Kim Smith Whitley

Thanks Ted. I am thrilled to be here today as part of the GBT team.

Over the years, I've developed a great respect for the Company as an investigator, a clinician and an advocate for patients. The shared dedication to sickle cell disease across the organization has made for a smooth transition, and I am proud to be joining GBT in its journey. I want to provide some additional perspective on current environment for treating sickle cell patients based on my experience and feedback from my peers.

For so many patients, including those that I have seen in the clinic, the challenges created by the pandemic have severely impacted their daily lives from employment to health care to family life and beyond. This dynamic extends the care seeking behavior. I am fortunate to have spent the last 29 years at Children's Hospital of Philadelphia, or CHOP, which is unique as a comprehensive tertiary care academic center that is very well staffed. Recently, the team there has seen some patients come back in for their routine visits. That is encouraging news, but for most sickle cell care settings, this is going to take more time. I would validate what Ted and DJ said about COVID vaccination among sickle cell patients. In my practice and others, it has been common for sickle cell patients to be hesitant initially about taking the vaccine.

However, we are hopeful, as with other vaccines that this will improve. That said, there's increasing momentum and information, more opportunities to get vaccinated and a decreasing risk of transmission over time. I do expect that a broader group of patients will return for in-person care. It's hard to say how long that will take. That will vary based on geography and care setting and man lag the general population. But one thing that I am extremely confident in is Oxbryta's place in the treatment armamentarium for sickle cell disease. With more experience using the medicine, I believe Oxbryta will continue on its path to becoming a standard of care for these patients. And while I'm very excited about Oxbryta, I'm even more excited about the future of GBT with an exceptional pipeline that I aim to continue to build and grow. I will now turn the call back to Ted.

Dr. Ted Love

Thank you, Kim, and welcome. We're so excited to have you as part of GBT.

Now let's get to the pipeline.

First, inclacumab, our P-selectin inhibitor that has the potential to be dosed quarterly, this is a very meaningful improvement for patients compared to the current option, which requires monthly dosing.

We are on track to initiate 2 Phase III studies for inclacumab by midyear. One is focused on reducing VOCs over a 48-week treatment period, and the other is focused on reducing 90-day hospital readmission following an initial BLC hospitalization. These two studies are designed to potentially enable two independent regulatory submissions for separate indications.

Moving to GBT 601, our next-generation hemoglobin polymerization inhibitor, we have enrolled participants in a healthy volunteer study, and our goal is to have proof-of-concept data in sickle cell patients by year-end. If the preclinical data for GBT 601 play out in the clinic, we believe it would be positioned as a best-in-class therapy with the potential to provide a functional cure in a one-daily pill. In the first quarter, we also bolstered our pipeline with the in-license of two early-stage small molecule programs from Sanofi. The mechanisms targeted by these programs are distinct from Oxbryta, expanding our long-term potential to transform treatment of sickle cell with multiple complementary therapies.

Turning now to our other growth initiatives. In the United States, we are seeking to expand the Oxbryta label to include children age 4 to 11. Expanding to younger patients is a top priority as we believe that mitigating red blood cell sickling and destruction early in life could modify the course of disease and alleviate serious and life-threatening complications.

Turning to Europe. We remain on track with the European Medicines Agencies continuing review of our marketing approval application, which we anticipate will be completed in the first half of 2022. Currently, physicians can gain experience with Oxbryta through our early access program for eligible patients in Europe and other regions outside the United States. In the sixth Gulf Cooperation Council countries in the Middle East, we are working with our partner, Biopharma EMEA to make Oxbryta available and we have a goal to establish a similar partnership in Latin America, including Brazil, for the bulk of the region's sickle cell patients live. Altogether, our label and geographic expansion plans are intended to give us the opportunity to reach more than 350,000 sickle cell patients around the world over the next several years. And as we make progress against this goal, we continue to explore strategies to bring Oxbryta to patients in limited resource geographies, such as Africa and India. In closing, GBT continues its leadership in cyclicality and is well positioned for long-term success.

We have near-term opportunities to expand into younger patients in the U.S. and to secure regulatory approval in Europe.

We also have a robust pipeline and two potential best-in-class medicine, in inclacumab and GBT601. I am proud to be part of the GBT team and want to thank our employees for their passion and dedication, which is essential to realizing the potential of our medicines.

We are unified in our commitment to the sickle cell community, and every day, we are getting closer to our goal of transforming sickle cell disease into a well-managed condition. With that, we'd like to open the call for questions. Operator?

Operator

At this time, we will be conducting a question-and-answer session. [Operator Instructions] Our first question comes from Alethia Young with Cantor Fitzgerald. Please proceed with your question.

Alethia Young

Obviously, it's around the launch.

So you've seen March, you've seen now April. It sounds like trends were softer in the first two months. I guess, to hit this like maybe growth in new scripts next quarter, like, what do you think kind of anecdotally kind of has to happen or continue to happen, is one part of that question? Obviously, the second part of that question is, just what you were seeing in March and April.

Dr. Ted Love

Alethia, this is Ted.

So obviously, we don't want to report on the next quarter quite yet, but I would just emphasize that we continue to feel very encouraged about where this is ultimately going to go. The biggest headwind for us continues to be that patients are not interacting with their doctors.

In fact, we have good evidence that in Florida and other places the physicians are actively telling the patients to stay home, not risk getting on public transportation, not risk being around people that increasingly are not wearing mask and get infected. But all this is going to turn around.

So we feel great about the long-term future, but we don't want to set expectations too early. What we've said all along is that we thought the second half of the year was really where we would expect growth. We really felt like the first half of the year would likely be flat, and we basically seen that.

Although we do feel that we can signal that, we think 10% to 50% growth in revenues in the second quarter versus the first quarter, we think that's very realistic for us, and we wanted to let everyone know that. And we are growing prescriptions, as we mentioned in the script.

We are actually increasing the number of patients each quarter that are on Oxbryta.

Operator

Our next question is from Akash Tewari with Wolfe Research. Please proceed with your question.

Akash Tewari

I have a few. I guess stepping back, why hasn't Oxbryta kind of launch well in severe patients who have high transfusion burden? Since theoretically, you're keeping these patients out of the hospital, has there been any effect on the Novartis launch where you kind of have a more immediate impact on VOC that may have limited uptake for Oxbryta? Number two, for 601, how come that compound hasn't been run head-to-head with Oxbryta in preclinical assays? And it seems like in terms of HB occupancy, it tops out kind of in the low 30s, but it does seem to have a pretty big difference in red blood cell half-life and hemoglobin level.

So what is going on specifically with that compound that's allowing you to do that? And why are kind of the occupancy rates topping out in the low 30s? And then kind of lastly, just you mentioned sequential growth of 10% to 15% in Q2.

You're also noting that there is a lot of vaccine hesitancy, and particularly in the African-American community, so what specifically gives you confidence on that 10% to 15% growth that you guided today?

Dr. Ted Love

Lot of questions. I want to make sure I try to walk through them all.

So not a lot of sickle cell patients are on chronic transfusion that can necessarily be stopped.

We have seen many people that are on chronic transfusions, discontinuing free to add to this from your experience. But for example, if somebody is on chronic transfusions due to stroke, those individuals may need to really stay on transition that we prove as we're trying to do in the HOPE-KIDS 2 Study that we're providing protection against stroke. But we have many, many patients, and we reported on this that many patients have reduced and/or completely come off of transfusions on Oxbryta. And those are patients that typically, you're transfusing them because you're trying to maintain hemoglobin levels that are more acceptable so the patient can have adequate energy to get around. They're not the patients that are necessarily on protocol due to our prior stroke.

So I think we are having success there.

Your question about hemoglobin occupancy, it didn't top out. That was the highest dose that we studied. It was 150 milligrams a day. We can actually get 100% modification, and we readily do it.

In fact, many of the animals in our tox studies actually have 140% modification. We can dose high enough safely that 40% hemoglobins actually accept to 601 molecules.

So we have a lot of luxury and capability to dose as high as we want. The reason we stopped at 30% is, you can see the animals are effectively cured, their reticulocytes counts are normalizing. Their hemoglobin levels are actually higher than the animals would sickle trait.

So the data really looks like you've essentially cured these animals, but we can go higher, but the data is unlikely to get much better than curative effect. And then finally, on the 10% to 30%, maybe I'll just defer to Jeff to see if you want to add any comments on that?

Jeff Farrow

Sure. Hi, Akash.

As there's a couple of things that are really impacting our comfort on that 10% to 15% range, the first one is really what Ted alluded to earlier in the prepared remarks is that there's a growing net number of patients that continue to be on Oxbryta. And as that number grows in the aggregate basis, we continue to see revenue growth.

So that's one aspect that we'll see as we emerge from Q1 into Q2.

The other aspect is, we do anticipate relatively flat, although we've seen that is improving coming out of the latter half of March.

So given the trends, we don't think, with some of the infection rates coming down that that is going to impact us on a negative basis.

So those are the real two major items. And then it seems like we're -- we don't have a long enough history at this point to sort of point to, but we do think days on hand is going to somewhere hover around the 20 to 22 days as opposed to what we saw at the year-end and having a resulting drawdown that impacted us here in the first quarter. We don't expect that in the second quarter.

Dr. Ted Love

And Kim, do you want to add anything regarding transfusions?

Dr. Kim Smith Whitley

So, Ted, I think that really, you said the main features of what we've seen, I just want to reiterate that those individuals who are on regular or chronic red cell transfusions for indications other than preventing neurologic complications have really been able to come off of transfusions altogether with Oxbryta or significantly reduced the number of units or the frequency with which they receive transfusion on Oxbryta.

So very encouraged by what we've seen in this population.

Operator

[Operator Instructions] Our next question comes from Ritu Baral with Cowen & Company. Please proceed with your question.

Lyla Youssef

This is Lyla on for Ritu. Maybe just and just to quickly ask you to follow-up on the current trends that you're seeing with adherence. I know you said it's within the range of typical analogs, but are you seeing an improvement and impact through the high-touch model? And then what proportion of your estimates for that growth of 10% to 15% in Q2 is driven by improvements in underlying compliance and adherence?

Dr. Ted Love

DJ, you want to take that?

David Johnson

Sure. Lyla, we are seeing adherence rates stable in Q1 to previous quarters.

So not a lot of news there. We're well within the range of the analogs that we've talked about in the past, of that 50% to 70% one year adherence rate.

So that hasn't changed.

You're referring to a bunch of tactics that we've talked about that we rolled out but most of those tactics rolled out in late Q4 or in Q1.

So things like that get started guides and brochures, the starter kits that include a bunch of adherence tools, such as the smart bottle cap stickers, the smartphone apps, that sort of thing. And then the high-touch model that we've implemented for all patients that come through our hub those all started really, in earnest, in Q1.

So it's a little early to have data on that, but we do have insights. We know, for example, the high-touch model works better than the low-touch model or no-touch model last year. We saw a lift in adherence for those patients that went through that program.

So that's why we've shifted to that this year.

So we fully expect all of these tactics to have a positive impact as we get into the second half of this year. We'll be sure to update you on that.

Lyla Youssef

All right. That's very helpful.

And so does that mean you're modeling that to be consistent in Q2 for those -- that 10% to 15% increase? Just want to make sure I understood you correctly.

David Johnson

Yes, yes, absolutely. That's -- it's the same adherence rates that we've been talking about, we would expect that in Q2.

Operator

Our next question comes from Gregory Renza with RBC Capital Markets. Please proceed with your question.

Xinyue Lu

This is Xinyue for Greg. It's great to see the broad payer coverage for Oxbryta so far. I was wondering, since there's usually a 6 or 12-month limit for Axis. How do you think about keeping patients on therapy when the reauthorizations are potentially coming up?

Dr. Ted Love

Great. I don't think that's actually been an area of concern, but DJ, you may want to elaborate on that?

David Johnson

Sure. Yes. The reauthorizations are actually a really good story for us. Most payers do want to check in at the 6-month mark or sometimes the 1-year mark to see how patients are doing. And it's usually a light prior authorization, where they check in with the physician. Usually, there's a list of things that they ask. And in our case, since we have a lot of really good metrics in our label around hemolysis and hemoglobin, that if any one of those things is in the positive direction than they have been approving therapy to continue.

So I'm not aware of any patients being discontinued through a reauthorization process at this time. It's been really good coverage and our ability to work through those. And then our hub, our patient support hub, GBT source solutions helps with the process in the sense that at year-end, for example, reauthorization of insurance of co-pays, that sort of thing. We were able to manage that ahead of the year -- of the year-end last year so that patients were aware of that, we could reset their co-pay assistance cards through our hub.

And so we really didn't see a significant drop off because of the reinitiation of co-pays and that sort of thing at year-end.

So we just plan ahead with our hub and able to see it coming.

So hopefully, that helps.

Operator

Our next question comes from Jason Gerberry with Bank of America. Please proceed with your question.

Jason Gerberry

So my question is, as we talk to physicians, it sounds like the coverage of Oxbryta is good. If there's one challenge for that it's an either/or decision between Adakveo and Oxbryta.

So if you have physicians who might be more favorable to , it may be challenging to get Oxbryta.

And so I'm just curious, is that mirrors your feedback, your understanding? And then as we look longer term, just trying to get your sense of the value of having Oxbryta and a selectin blocker, both in-house with your own portfolio and being able to kind of manage both of those and perhaps drive better access that way? Just curious.

Dr. Ted Love

Right. Well, DJ, you may want to comment on anything you've seen in the field, but I would just say that the first point to keep in mind is the drug actually -- these drugs actually have different indications.

So there really isn't a scientific reason that a payer would object because Adakveo is indicated to reduce the number of VOCs. Oxbryta Is actually approved to treat the underlying nature of sickle cell disease, really with the intent that you will improve oxygen delivery, protect organs from the inevitable death that we see of organs and the premature death of the patient.

So they are truly different indications. And I know there are patients that are being prescribed both drugs.

Now a physician might think that the VOC is the bigger issue that they want to focus on first and they want to use Adakveo first. But that really shouldn't, I think deter a physician wanting to treat the underlying disease because these patients typically are dying in their 40s, in their 30s and 40s. And that's really what we're trying to change by fundamentally treating the polymerization, but DJ, if you had any one thing to add from a payer perspective?

David Johnson

Yes.

Just to remind folks that we have about 40% to 50% of our utilization of Oxbryta is in combination therapy. And a lot of that's hydroxyurea, but a fair amount of that is already with Adakveo the low double-digit percent is actually in combination with Adakveo.

So Ted is exactly right. There's no kind of mechanistic reason these can't be used or indication reason they can't be used together. And in fact, they are being used together in some patients. That said, there's not a lot of clinical data of them being used together.

And so a payer will oftentimes ask a lot of questions about new therapies without a lot of data.

So yes, there tends to be prior authorizations and maybe a couple of extra steps to get approval, oftentimes an appeals process. But generally, when the physician and patient really want to get that combination used, and they work with our hub and our patient team, we're generally able to get it approved. It just takes a few more steps until we have more data.

Operator

Our next question comes from Andreas Argyrides with Wedbush Securities. Please proceed with your question.

Andreas Argyrides

Our question is around telemedicine how much of sales in the first quarter can be attributed to telemedicine? And then if the pandemic persists longer than anticipated, what are your strategic plans to I guess, leverage telemedicine efforts in that case?

Dr. Ted Love

It's a great question. I mean we've actually always assumed that we would work to make telemedicine work because physicians are using it.

In fact, I think many people think telemedicine is going to continue to be part of medicine going forward after the pandemic.

So making that work well is something that's important to us. There is some limitations, however, among physicians around starting completely new drugs in the setting of telemedicine.

Some physicians are perfectly comfortable with that. And we've obviously had more success with those physicians than with physicians that are reluctant to do it. But quantitatively, DJ probably has some data on that, that you could share with you.

David Johnson

Yes. And just a few of the figures, we have seen an increase in our overall engagements with physicians in Q1. March was our strongest month in Q1. And our field activity, in general, both telemedicine and face-to-face, did go up in Q1. Actually, our engagements are back to pre-COVID levels.

So the number of interactions with health care providers in Q1 and reached pre-COVID levels.

Now the majority of those interactions still are through telemedicine, we are getting more and more face-to-face depending on COVID dynamics in the geographies, but we are fully set up and operationalize. And we're very early on in last year in the pandemic at becoming operational in a telemedicine world.

So all of our materials, all of our education are strong focus on social media and digital for education as well, it's all set up for this environment. But Ted is exactly right, our preference is to do some more in-person because that tends to also mean patients who are in-person. And we do have our internal data that shows that both when our reps are in person and when the patients are in person, it's easier for a physician to get educated and to prescribe Oxbryta.

So that's our preference is to work diligently to have more in-person engagement. But should the pandemic continue to proceed as is, we're fully ready and able to continue to operate in this environment as long as necessary.

Andreas Argyrides

And you -- and this is not an extra question -- just reiterating the prior one. Can you break out sales from telemedicine or...

David Johnson

We really can't. We can't really -- so when a prescription comes in, there's no way of knowing if the physician was seeing the patient through telemedicine or not on the prescription itself. What we do know is we saw a significant increase through the pandemic in electronic submissions of prescriptions to our hub and generally, that we -- in talking to physicians, that's associated with having more virtual engagements with patients where they are doing everything digital.

And so clearly, they're doing more prescriptions through telemedicine than they ever have before, but the preference is still to do in-person.

Operator

Our next question comes from the line of Danielle Brill with Raymond James. Please proceed with your question.

Danielle Brill

So I guess, maybe if you could just help me understand a little bit more about your guidance for flat NRX in 2Q.

If you were seeing an uptick -- or if the majority of your NRx came in March and then I think you mentioned you saw an uptick late in March, I'm just curious why you're not confident that, that trend will continue over the course of 2Q? Are you just being conservative? Or is there more to this dynamic that I'm not understanding?

Dr. Ted Love

No.

I think -- I mean, the truth is, Danielle, this is Ted. I mean, these things are very choppy. And obviously, we're not getting the kind of growth that gives you confidence to predict the numbers will go up quarter-over-quarter. And we think it's really prudent to kind of stay with what we've been saying, which is the enrollments are likely to stay in this 1,000 range. We may be a little under, we were 950, I think, the last two quarters. We might be a lower, but we're not going to get to the kind of growth that we need to get to until patients start going back into doctors. And quite frankly, doctors allow their patients to come back in to be seen directly.

So we think that, that number is not really conservative. We think it's realistic though. And we've proven our capacity to be at those numbers in the setting of the pandemic. What we need to happen, quite frankly, is not only -- it's not just for COVID cases to go down, we need patient behavior to change.

So the cove cases could go down, but the patients are still not going in to the doctor. That's really the triggering event for us.

Now we expect all that to happen, but we don't know the exact timing.

So we're comfortable holding to 1,000, as DJ said, which is really through telemedicine primarily.

Operator

Our next question comes from Yanan Zhu with Wells Fargo. Please proceed with your question.

Yanan Zhu

Just to have a quick one.

I think in the past, you provided a number of patients on therapy. I might have missed this, but did you give the number of patient on therapy this quarter?

Dr. Ted Love

No, you've never missed because we've never given that.

Yanan Zhu

Any reason for no longer providing that number?

Dr. Ted Love

Well, I mean, we have, obviously, like many companies, a thoughtful process for figuring out which metrics to report and we kind of worked through that, quite frankly, with our Board as well on the metrics, and we continue to talk about it. But that's not a metric that we've ever contemplated reporting on. The metric that we want to get to, quite frankly, is revenue guidance, that's what we're trying to get. And that's going to be a much simpler metric. It's just hard for us to get there in the midst of pandemic. But the metric we want to give you, quite frankly, looking forward is revenue.

Operator

Our next question comes from Ben Burnett with Stifel. Please proceed with your question.

Unidentified Analyst

Hi, this is [indiscernible] on for Ben. I was just wondering if you guys can provide some color on the refill rate that you're seeing and maybe the average number of bottles per patient during the quarter?

Dr. Ted Love

Again, I think those are metrics that we have not reported in the past. And I don't know if Jeff, do you want to add anything to that, but those are not metrics that we've reported and want to take on as an obligation to report every quarter.

David Johnson

Yes. Maybe one thing I will add, this is DJ, is that we continue to have good process times and cycle times, two weeks or less from the time the prescription comes in to get fully worked up prior off and shipments to a patient.

Our conversion rate from a script to a bottle is still high, 75% or so. And our compliance rate is still high, meaning that we've always said that once a patient starts on therapy, they generally take it as prescribed and refill that bottle within that 30-day window.

We continue to see that. Persistency is the other piece of adherence that we look very closely at, and that's something that every chronic therapy is always working on. And that's -- those two things together, compliance and persistency make up that adherence range that we talked about, that 50% to 70%.

So hopefully, that's helpful.

Operator

Our next question comes from Paul Choi with Goldman Sachs. Please proceed with your question.

Paul Choi

Great to have Kim on the call. And Kim, I guess, as a clinician transitioning to industry here, could you maybe just sort of comment on what -- as a clinician, you'd like to see for the early 601 data later this year? And then as we go into patients after healthy volunteers, just sort of framing some guideposts there?

Dr. Kim Smith Whitley

Thank you for that question, Paul. I really would like to say that the hope for 601 is that we will continue to see data that suggest good, better comparisons to what we've seen with Oxbryta. And I think that we hope that we will see data that support that 601 will continue to have a same but stronger impact to Oxbryta and we might even look to see whether or not there are changes in some of the side effect profile.

So I think that, that's what we're going to be focusing on for the end of this year.

Operator

Next question comes from Yatin Suneja with Guggenheim Partners.

Our next question comes from John Newman with Canaccord Genuity. Please proceed with your question. John, are you there? Okay.

Our next question comes from Yatin Suneja with Guggenheim Partners. Please proceed with your question.

Yatin Suneja

Can you hear me now?

Dr. Ted Love

We can. Yes.

Yatin Suneja

Perfect. Can you provide some color on the penetration you might be -- or you might have achieved in various subset of patients like patients that have hemoglobin below 8% or patient below 10.5% or maybe above that.

If you can give some sort of a commentary there? And then maybe a broader question, if we step back and think about, let's say, peak market share, do you envision Oxbryta treating a similar number of patients that gets hydroxyurea? I think it is our understanding that about 25,000 to 30,000 patients are on hydroxyurea in any given year.

So can you reach that level with Oxbryta and in what time frame?

Dr. Ted Love

Those are great questions, John.

And so I would say, at a high level, we've always felt that getting to those levels. Is achievable because, quite frankly, the data suggest that Oxbryta has a better safety efficacy profile? It doesn't have a black box warning around cancer risk. Patients feel better on the drug very quickly. And the side effect profile, as you know, is better.

So we definitely think, long term, getting to that level is achievable. It's obviously all been delayed significantly by COVID, but we do think that's the bogey long term.

In terms of penetration in the various subgroups, my sense is that we're very early in all of these, that's good news. We've still got a lot of growth in every segment, whether people with high hemoglobins or low hemoglobins. But as DJ said, we're already seeing the prescriptions for Oxbryta begin to really reflect the label, which is it's for treatment of individuals above 12 years old to treat their underlying sickle cell disease. Quite frankly, your hemoglobin should not be a barrier, and ultimately, it won't be a barrier. But DJ, do you want to speak anything quantitatively about subgroups? I know it's early.

David Johnson

Yes, we do a chart audit and claims database audit with over 2,500 patients. And that's where we get our figures that over 50% or approximately 50% of our patients on Oxbryta had a baseline hemoglobin greater than 8 grams per deciliter.

So about 50% were less than that and so looks like physicians are comfortable using Oxbryta in many different hemoglobin levels.

We have patients that are above 10.5 in that database, baseline hemoglobin.

We have patients that are between 9 and 10.5 in and we have patients, of course, between 8 and 10.5.

So we have a broad utilization of Oxbryta, which we think is great. We certainly are indicated for all patients with sickle cell disease.

The other penetration number we're certainly excited about is that only about 25% of the patients in the practices of the physicians that have tried Oxbryta to date, that 1,550 prescribers, only about 25% of their patients have been utilized Oxbryta on.

So we still have 75% of our existing treaters patients for Oxbryta to be used in. And that's a great opportunity to go deeper with physicians that already have experience with Oxbryta.

So you can imagine that's a big focus of ours. And we also are looking to penetrate into more physicians coming online as -- in this quarter to prescribe Oxbryta for the very first time.

We have a large target list, but new prescribers we're still developing.

Operator

Next question comes from Matthew Harrison with Morgan Stanley. Please proceed with your question.

Matthew Harrison

So I guess I have a sort of -- I'm just looking for your perspective on sort of a longer-term question, which is as follows.

So we've obviously been talking about throughout the whole pandemic how patients aren't going in and -- but it does sound like physicians at least have some sort of interaction with patients.

And so I guess my real question is, once patients start to go back into the office, why isn't there going to be a large bolus or a significant backlog that has building -- are physicians keeping list, things like that? I'm just wondering why we wouldn't see a very significant snapback in terms of growth once you start to see large numbers of vaccinated patients heading into the office.

Dr. Ted Love

Yes. No, it's a nice aspirational question, and we love that. And Matthew, that may happen. It's just that as for a guidance perspective, we're not really sure what's going to happen after the pandemic. We're not really sure if people are going to continue to be somewhat conservative for a while. I do think that you are right that as we educate more and more physicians about Oxbryta and they have the intention of using it and they have a group of patients they haven't seen, that would represent certainly a potential reservoir of individuals. We just don't know what the curve looks like. And that's why we want to be thoughtful about not trying to set expectations that we don't deliver on. Because at the end of the day, this is going to really be driven by the patients getting back into the office and having that interaction to get to prescriptions.

Operator

Our next question is from Joon So Lee with Truist Securities. Please proceed with your question.

Joon So Lee

And a lot of the questions have been asked, but maybe the recent deal with Vertex that they did with the genome editing drug for sickle cell disease in, CTX001 specifically implied that the opportunity for that drug must be large even for an expensive genome editing drug and imply possibly tens of thousands of sickle cell disease patients may be addressed. Is that a reasonable interpretation? And if so, should we be trimming down the total addressable market for sickle cell disease? And this also applies to 5-or-so other additional companies pursuing similar functional cures.

So I'm just curious what your perspectives are on that?

Dr. Ted Love

Yes, Joon. Thanks for the question. It's hard for me to comment on Vertex and how they model their business. I can tell you that from my perspective, I think if you could provide effectively a cure with a pill, that's very safe, that's going to be extremely attractive. And that's what we're really focused on doing. And as Kim said earlier, we think we can figure a lot of that out, quite frankly, fairly quickly, because the evidence that you've cured a patient is really pretty much ascertainable by looking at their red blood cell health and red blood cell function.

So we think we're going to figure that out fairly quickly. If we could make gene therapy as simple and safe as vaccination, for example, I think that would be very, very attractive, but unfortunately, that technology does not exist. And when that technology exists, quite frankly, GBT is likely to to be involved in that. But right now, given the ablation, given the long hospitalization, given the risk of cancer and other things after these big ablated procedures, we think, a safe pill based curative therapy would be the winning therapy.

Operator

And our last question comes from Raju Prasad with William Blair. Please proceed with your question.

Samantha Corwin

This is Sammy on for Raj. I was wondering if you could provide a data point on the average number of prescription a single prescriber is prescribing? And then, I guess, if you could provide any color on two small molecules you recently licensed from, and how they complement or overlap with the use Oxbryta or your other pipeline assets?

Dr. Ted Love

Okay. Sammy.

So I'll take the first one and then defer to DJ on the first question, and I'll take the second.

So the Sanofi molecules that we brought in are small molecule targets and the program actually already has molecules which are active against the targets and significant amount of data supporting that activity. We don't disclose the specifics of our targets, but I would say that they are both highly complementary with Oxbryta and would become many with 601.

So they work through a distinct mechanism. One is really more focused on polymerization. And the other is more focused on inflammation, which we think would have more of a direct relationship to VOCS, the pain crisis.

So there are two distinct and complementary targets even though we haven't really delivered publicly what exactly the targets are. We're very excited about them, but they are early stage, but complementary. DJ?

David Johnson

Yes.

In terms of number of prescriptions for rider, so in totality, about half of our existing riders have written for more than one patient. But that's really being driven by kind of the low deciles in that sample that are just getting started at using Oxbryta. When you look at the higher decile physicians with more experience and more patients, it's much higher than that. It's greater than 75% of them have prescribed Oxbryta for more than one patient. On average, riders for over -- about 3.5 patients launched to date and that's still growing. Those higher decile doctors, it's over six patients per prescriber.

So it's one of these situations, of course, physicians have more patients and more urgent need are going to get more experience. And they seem to like the response as the real-world evidence would support because they write it for multiple patients.

Operator

We have reached the end of the question-and-answer session. At this time, I'd like to the call back over to Ted Love for closing comments.

Dr. Ted Love

Thank you, everyone, for joining the call today.

Let me close by reemphasizing that all of us at GBT are very optimistic about the future. We look forward to further expanding adoption of Oxbryta, advancing our pipeline and supporting the sickle cell disease community as we work to transform the lives of patients for the better. We hope you continue to stay safe and healthy. Please reach out if you have any additional questions.

Operator

This concludes today's conference.

You may disconnect your lines at this time, and we thank you for your presentation.