Hello and welcome to the BioMarin Pharmaceutical Third Quarter 2023 Conference Call. All lines have been placed on meet to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] I will now turn the conference over to Traci McCarty, Head of Investor Relations. Please go ahead..

Thank you, JL, and thank you all for joining us today.

To remind you, this non-confidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical, Inc., including expectations regarding BioMarin's financial performance, commercial products and potential future products in different areas of therapeutic research and development.

Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors, and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, such as 10-Q, 10-K and 8-K reports.

On the call today from BioMarin's management team are JJ Bienaime, Chairman and Chief Executive Officer; Jeff Ajer, Executive Vice President, Chief Commercial Officer; Hank Fuchs, President, Worldwide Research and Development; Greg Guyer, Executive Vice President, Chief Technical Officer; and Brian Mueller, Executive Vice President and Chief Financial Officer.

We do plan to end this call promptly at 2:30 p.m. Pacific Time, and we thank you for your understanding. I will now turn the call over to BioMarin's Chairman and CEO, JJ Bienaime..

Thank you, Traci. Good afternoon, good morning, everybody. As you will have seen this afternoon, we announced that I have decided after over 18 years with BioMarin to retire as the Chairman and Chief Executive Officer, effective December 1st of this year. And as many of you are aware, I recently actually turned 70, I cannot believe it myself.

So I will not - will not be a surprise to you that succession planning has been underway with the Board over the past several years. These announcements and the appointment of Alexander Hardy to succeed me as CEO, follows a thorough multiyear planning process.

Together with the Board, we conducted a comprehensive search over the past year, and we are thrilled to have Alexander step into the role. As part of this transition, I will also step away from my position as Chairman of the Board of Directors.

However, I will continue to serve on the Board until the 2024 Annual Meeting of Stockholders, and I will stay as a consultant to the company for the remainder of 2024. I look forward to working with Alexander and the Board during this period to ensure a smooth transition.

I'm pleased that our lead independent director, Richard Meier, Randy will be our new Chair of the Board. When I joined the company in May 2005, we had just one marketed product and recorded about $26 million in annual revenues.

Since then, our team has developed and commercialized seven additional medicine, pioneered groundbreaking first and transform the lives of complex of patients.

BioMarin is now a profitable, fully integrated industry leader and one of the most successful biotech company with annual revenues anticipated to be more than $2.4 billion this year and also expected to grow to close to $3 billion next year. BioMarin is extremely well positioned for substantial future growth and profitability.

Our market cap has grown from around $300 million, when I started as CEO to more than $15 billion today. Our stock price went from $6, when I joined a CEO 18 years ago to over $83 today at the close, so we have generated returns greater than the XBI Index over the past one year, 2 years, 5 years and 18 years.

BioMarin is now a profitable, fully integrated industry leader with annual revenues of more than $2 billion and extremely well positioned for substantial future growth and profitability. We have expanded from operating only in the United States.

When I started with the company is now - at that time 300 employees to setting our medicine in almost 80 countries around the world and more than 3,000 employees. As the company exposed for its next phase of growth with the recent introduction of VOXZOGO and ROCTAVIAN this is the ideal time to hand over the reins to the next leader.

In the search, the Board focused on finding a successor with experience driving commercial growth and operational excellence, while at the same time bringing a deep understanding of the science and a strong background in product development.

We are confident that Alexander perfectly meets those criteria, as CEO of Genentech, Alexander led the commercialization of 10 new products in therapeutics areas, including cancer and hemophilia. Serving as CEO of this industrial leading innovative and impactful the company over the past 18 years has been the highlight of my career.

We have built an incredible organization with great potential to be further unlocked by Alexander and the team where I will miss working with our talented and inspiring employees day in and day out, I am confident that the company is well positioned for future success.

So to those on the call today, thank you for your engagement and support over the years. I still also want to emphasize that I will still be involved with the company, and I will still be very involved with biotech in general, as you will find out in the future. So now let's turn back to the quarterly results.

So we are very pleased with the results in the third quarter. Recording 15% total revenue growth compared to the third quarter last year and continued strong growth in earnings per share faster than revenue. These results were driven primarily by VOXZOGO, which remains on track to become our first blockbuster products.

We saw strong demand and uptake in the quarter, and we expect this trend to continue. In the third quarter, more than 300 additional children become – began treatment with VOXZOGO since the end of Q2, and additional strong growth is expected in Q4.

As a result, today, we increased full year 2023 VOXZOGO guidance to between $435 million, $135 million and $465 million.

With the recent US and European approvals of VOXZOGO's age expansions, all ages in the US and for children ages four months and older in Europe, over 1,000 additional children now have the opportunity to benefit from a longer VOXZOGO treatment window.

We are also pleased to share that based on increased fill-finish manufacturing commitments, VOXZOGO supply is planned to increase from '23 levels to the first and second quarter in 2024, and is expected to be fully unconstrained by midyear 2024.

Moving now to ROCTAVIAN, where we have made tremendous progress building and connecting the network that will facilitate patient treatment, we'll be laying the groundwork for our patient access to ROCTAVIAN has taken time but has been an essential step to ensuring access and reimbursement.

Well over 100 people have been tested for ROCTAVIAN and AAV5 eligibility globally, which is the first step that a patient needs to do to determine if he can be treated with ROCTAVIAN. The zero negativity rate on the samples that were tested to-date is approximately 70%.

So, 70% of the patient tested that are eligible for ROCTAVIAN, they still need to have liver scan, but most of the eligibility comes from the AAV5 positivity. And we expect the testing momentum to continue as awareness and access increases.

While it has taken more time than anticipated to give global health care system wired to facilitate ROCTAVIAN treatment, we remain encouraged by the high level of interest and demand from patients, physicians, patient advocacy groups, hemophilia treatment centers, and payers.

In Europe, we had strong progress in the quarter and expect to have final German and Italian prices for ROCTAVIAN published by year end. And in the US, significant momentum connecting the network to treatment is occurring. Jeff will provide more detail on launch progress and our updated expectations for ROCTAVIAN.

Turning to BioMarin's record year-to-date revenues of nearly $1.8 billion in the first nine months of the year. This represents 14% year-over-year growth even with lower than expected contributions from ROCTAVIAN.

These results underscore the strength of our business and the achievement of double-digit revenue growth and our profitability objectives as set out at the start of the year. The business is poised for strong growth in '24 and beyond.

With VOXZOGO continuing to exceed expectations - sorry, ROCTAVIAN access reimbursement in place for a meaningful uptake next year, we believe BioMarin revenues are set up to approach $3 billion in 2024. In summary, we have built an industry-leading company.

Strategy to create a sustainably profitable and growing business that provides patients with innovative and essential medicine is coming to fruition. The future looks very bright for BioMarin, and I want to thank my colleagues for the tremendous collaboration and fort we have built together. Thank you for continued support.

I will now turn the call over Jeff Ajer to discuss the commercial business update.

Jeff?.

Thank you, JJ, in so many ways. I'm very pleased with our commercial performance in the third quarter, resulting in $581 million in total revenues and representing 15% growth year-over-year, including KUVAN and 20% growth excluding KUVAN.

Turning to VOXZOGO, as JJ mentioned, today, we updated full year guidance to between of $435 million and $455 million, representing approximately 165% year-over-year growth at the midpoint.

Appreciating that the run rate for the fourth quarter and full year 2023 may seem conservative based on VOXZOGO revenues of $123 million in the third quarter, we note the impact from supply constraints discussed last quarter continue to limit growth through the end of this year.

While we continue to closely manage new patient growth and limit inventory stocking, we expect to fulfill smaller orders from various regions in Q4, while at the same time, adding hundreds of new patients in the fourth quarter.

As a reminder, new patient starts with VOXZOGO in the fourth quarter will represent only a fraction of a full year revenue patient in 2023. Importantly, we expect approximately 2600 patients to be receiving VOXZOGO treatment by year end 2023.

VOXZOGO supply is planned to increase from 2023 levels through the first and second quarters of 2024 and is expected to be fully unconstrained by mid-year next year. These commitments will ensure that we have ample supply to exceed full year 2024 consensus currently at $624 million and support growth beyond 2024.

At the end of the third quarter, more than 2,300 children with achondroplasia in 38 markets were being treated with VOXZOGO. Uptake to-date represents 12% penetration of indicated patients in BioMarin's commercial footprint, highlighting the significant growth potential remaining.

With the opportunity now treat up to an additional 1,000 children following the recent age expansion approvals in the US and Europe, we look forward to the possibility of the youngest children in these regions benefiting from VOXZOGO therapy. Turning now to ROCTAVIAN.

We are pleased to share that the second commercial basin was treated today in Germany. As JJ highlighted, we continue to make progress connecting the network that will facilitate treatment. 2023 has turned out to be the year of building that network to ensure and support meaningful patient uptake in 2024. Starting with Europe.

We have tentative agreement with the German National Association of statutory health insurance funds, or GKV, on the final German price for ROCTAVIAN, which we expect to be formalized and published by the end of the year.

As we have said previously, we believe this important step given the unique treatment and reimbursement profile of ROCTAVIAN will open up the access funnel with treatment in Germany. We are pleased to share that in Germany, 60 people are known to be eligible based on CDx testing for AAV5 antibodies.

The vast majority of those are in follow-up for net steps. As expected, the serine activity [ph] rate of about 70% is in line with our steady results and consistent with expectations. We are also pleased to report that there are now 10 sites in Germany testing for eligibility.

For the large pool of eligible patients and the final German price expected to be published soon, we are optimistic about patient uptake rates in 2024. Important to note is that the first patient treated resulted in net revenue of approximately $800,000.

Gross to net revenue adjustments going forward, under the GKV agreement will be different than for the first patient reported, but our overall expectations are to maintain similar net revenue per patient in Germany noting the impact of weight-based dosing and variable weight of patients.

In Italy, negotiations with the Italian Medicines Agency are going well and we expect to have a final price published by year-end. Italy represents then our second major European market that has agreement on price and reimbursement, opening the door to ROCTAVIAN access likely in early 2024.

We continue to work with the authorities in France and expect pricing negotiations to extend into 2024. It has taken several months in the US following approval to align stakeholders and to facilitate first patients treated. In general terms, this is a result of that unique profile of one-time reimbursement and treatment with ROCTAVIAN.

Navigating hospital administration and finance adds a level of complexity for hemophilia treatment centers or HTCs, leading to the final step of patient treatment with ROCTAVIAN. We expect that these administrative steps taken at the HTC level, while time consuming our one-time events and essential to facilitate patient access going forward.

In short, the ground work completed in 2023 is expected to enable simplified access to ROCTAVIAN drive more and more AAV5 eligibility testing and giving us confidence in the prospects for 2024.

However, we're less than 2 months remaining in the year and the holiday season beginning soon, we are lowering full year ROCTAVIAN 2023 guidance to less than $10 million.

Moving now to specific steps completed this quarter, starting with the issuance of coverage policies across payers, both private and public, we are pleased to share that nearly two thirds of all covered lives in the United States have been issued coverage policies to date, representing approximately 205 million people.

Importantly, the vast majority are in line with label or clinical trial criteria and are thus favorable in meeting expectations. Additionally, we are encouraged by the rapid uptake of the outcomes-based warranty with signed warranties in place representing more than 95 million US lives.

We have also received notice that the J-code for ROCTAVIAN has been assigned effective January 1, 2024. The permanent J-code is expected to accelerate payers prior authorization review process, ultimately speeding time to patient treatment.

Taken together, these developments are a strong indication of the value to the US health system places in a cost-effective one-time gene therapy. As we stated in our approval in Q2 earnings call, we expect it could take patients two to five months to complete the steps necessary before treatment with ROCTAVIAN.

The commercial team has been hard at work implementing a number of tactics to prepare physicians, HTCs and patients for the opportunity to benefit from ROCTAVIAN. With respect to site readiness, HTC are being prepared and educated on how to administer ROCTAVIAN.

We have targeted the largest and most capable HTCs for site readiness by year-end, a number of which have readiness plans before the end of this year. Increasing HCP and patient awareness in the US was also an important focus in the quarter.

A number of activities were conducted, including national HCP and patient webinars and the third annual Global Gene Therapy Scientific Summit sponsored by BioMarin. We are especially encouraged by the number of local patient advocacy groups which have been willing to host branded patient awareness programs for ROCTAVIAN.

Medical eligibility, including CDx testing is underway. And as a result, the US patient funnel is beginning to take shape giving us confidence in the prospects for treating patients going forward.

In conclusion, we are on track to achieve 2023 full year total revenue guidance driven by the strength of our inside product revenues and continued high demand for VOXZOGO globally.

Looking ahead, we believe the network built to facilitate treatment with ROCTAVIAN combined with our high expectations for VOXZOGO and strong enzyme business will enable BioMarin to approach close to $3 billion in total revenues in 2024. Thank you for your attention, and I will now turn the call over to Hank to provide an R&D update.

Hank?.

Thanks, Jeff. Thank you, JJ. The privilege has been ours. And thank you all for joining us today. We provided a thorough update on our earlier stage pipeline at R&D Day in September. So if you missed it, please find the full presentation on BioMarin's IR website.

Starting with VOXZOGO in the quarter and shortly beyond, we received some important updates from global health authorities, resulting in expanded access to children - younger children in both the US and where it is now approved in all age groups and in Europe for children four months of age and older.

We're gratified that the youngest children now have the possibility of greater potential, long-term benefits from treatment of VOXZOGO.

And I want to thank not just the usual clinical and regulatory teams at these finish line efforts, but also the extended BioMarin team of safety professionals, biometrics professionals, operations, pharmacology, really the whole entire fully integrated team played a strong role in enabling this advancement and access to patients.

So on behalf of the families and children with achondroplasia, thank you all. As mentioned last quarter, we have solidified our plans to begin the pivotal program using VOXZOGO for the treatment of hypochondroplasia with a natural history arm of the study expected to begin this quarter.

The pathogenesis and epidemiology are similar between achondroplasia and hypochondroplasia.

Well, hypochondroplasia presents with a milder phenotype in some patients in terms of short stature disproportionately and clinical manifestations, we plan to target the population with the most severe form of the disease, and therefore, the highest unmet need with high deficits beyond three standard deviations below the means.

With alignment from FDA on a single registration enabling 52 week randomized double-blind, placebo-controlled study with a primary outcome of annualized growth velocity, we look forward to initiating the treatment arm of the study in 2024, following the natural history running portion.

In addition, we plan to initiate two new clinical programs next year with VOXZOGO, one in idiopathic or polygenic short stature and the other in defined genetic short stature conditions. We know that CNP is a pivotal physiologic stimulator of endochondral bone growth on the level of the growth plate.

Further, human genetic studies of CNP and not FGFR3 demonstrate that even modest nudges and CNP signaling have a significant impact on final adult height.

This supports our confidence that VOXZOGO can deliver on the transformational improvement in growth across many forms of skeletal impairment, while retaining the strong safety profile demonstrated in achondroplasia. For these reasons, we look forward to starting the clinical programs in these additional statural [ph] indications in 2024.

Please take a look at the full R&D Day presentation for the latest update on our seven portfolio candidates discussed in September, and we look forward to keeping you apprised as they progress through development. And thanks for your support, and I'll turn the call over to Brian to update financial results in the quarter.

Brian?.

Thank you, Hank, and thank you, JJ, as well. Please refer to today's press release, summarizing our financial results for full details on the third quarter of 2023.

Since JJ and Jeff spoke to our revenue performance for the quarter and future revenue outlook, I will primarily focus on the remainder of our P&L and other key financial updates this quarter. As usual, all results will be available in our upcoming Form 10-Q, which we expect to file tomorrow.

We are pleased with our year-to-date revenue growth of 14% and non-GAAP earnings per share growth of 33%, which well positions us to achieve our top and bottom line financial objectives in 2023, as indicated by our narrowed guidance provided today on total revenue and earnings per share.

As underscored in today's guidance updates, we continue to expect double-digit revenue growth coupled with meaningful P&L leverage with GAAP and non-GAAP earnings per share growth faster than revenue. Moving on to Q3 results.

BioMarin's $581 million of total revenue in the third quarter of 2023 grew 15% compared to the third quarter of 2022 and 19% on a constant currency basis.

VOXZOGO strong performance and healthy growth in the enzyme products marketed by BioMarin drove this result, with some partial offsets of lower KUVAN revenue due to continued generic competition and Aldurazyme timing of order fulfillment to Sanofi.

The strength of our portfolio consisting of eight commercial products allows us continued patience on the pioneering nature of the ROCTAVIAN launch.

Specifically the ability to maintain our original full year 2023 total revenue growth expectations, which represents 16% of year-over-year growth at the midpoint, and our implied Q4 2023 growth rate at the guidance midpoint of over 20%. We remain confident in the long-term prospects of ROCTAVIAN and its potential to drive growth in 2024.

With respect to gross margin, Q3 2023 gross margin of 78.5% is an improvement of 1.6 percentage points as compared to the third quarter of 2022. R&D expense in Q3 2023 was $191 million, and SG&A expense was $224 million, which combined together totaled $415 million and grew 11% versus last year.

As compared to 15% revenue growth in the quarter, this aligns with our goal of growing operating expenses slower than revenue to deliver operating margin expansion for the full year. The increase in R&D and SG&A was primarily driven by the development of our early stage pipeline and global commercial launch activities for VOXZOGO and ROCTAVIAN.

As we look ahead to the fourth quarter, we anticipate that total SG&A and R&D expense will be higher than Q3 on a dollar basis due to the same drivers. Moving down the P&L. We continue to see an increase in interest income due to higher yields on our cash and investments.

On tax expense for the quarter, I will note that we recognized tax expense at a lower effective rate during Q3 due to some discrete tax benefits during the quarter.

This lower tax expense in Q3 will likely modestly benefit the full year tax as well, but we continue to project that our global annual effective tax rate will be in the 20% to 23% range over the next few years.

On the bottom line, we delivered on our commitment to profitability with $40 million of GAAP net income in Q3 '23 and $89.5 million of non-GAAP income. This level of profitability for Q3 and year-to-date gives us confidence to achieve our stated objectives of sustained and growing profitability on a full year basis going forward.

Year-to-date, 2023 non-GAAP diluted earnings per share has increased 33% as compared to Q3 year-to-date last year. And today, we have reaffirmed our midpoint guidance for non-GAAP diluted earnings per share for the full year.

In closing, we are on track to meet our top line and bottom line objectives for 2023 and beyond with strong double-digit growth in both revenue and profitability.

The continued success of VOXZOGO, the momentum building for ROCTAVIAN and ongoing margin expansion efforts gives BioMarin a strong foundation to achieve our financial goal of being one of the industry leaders in revenue growth and margin expansion as we close 2023 and head into 2024.

Thank you for your attention, and we will now open up the call for questions..

Thank you. [Operator instructions] Your first question comes from the line of Salveen Richter of Goldman Sachs. Your line is open..

Good afternoon. Thanks for taking my question. And JJ, it's been a pleasure working with you. Good luck on the next venture here. With regard to my question, you talked about the ROCTAVIAN, the HTC preparedness that's required? And then you also provided some context of two to five months to prepare patients for treatment.

Can you just break that down for us, like the time period needed for HTC, the - then kind of the payer dynamics that will play out the diagnostic aspect as well? And how demand is stacking up as you get a sense from physicians and lease centers right now? Thank you..

Hey Salveen, I'll take a shot at that one. There's a lot of moving parts in this launch. There is the specific HTC dynamic which is not unique to ROCTAVIAN. So, you may be getting some insights into how that's playing out in a parallel launch in the United States.

The HTCs need to be prepared both for the administration of a one-time treatment with ROCTAVIAN, which includes handling a frozen product, a very high value, it includes other dynamics like 340B discounting and pricing, relative in some cases, to larger health care systems that may be a parent organization and have some capabilities that the HTC does or does not have.

So, there's kind of those dynamics inside of the HTC. There's also the payer dynamics going on, which you would expect anyway in the United States. But in this case, the payer dynamics are complicated by the fact that gene therapies in a high-value, one-time treatment are new and different.

We've known and expected the payers will take some time to get their hands around that issue for years, and we've been preparing for that eventuality. There's also patient awareness and interest in a highly competitive and very dynamic changing standard-of-care environment. There are physicians that have a number of options available to them.

There's all those dynamics going on in parallel and we're navigating all of those issues in parallel. Some are taking some time. I mentioned the payer dynamics, specifically, what I believe is that the two-thirds of US population with issued coverage policies four months after approval, I think is really encouraging and very, very fast.

The uptake of the warranties, which is a brand new thing for payers at the levels that I described is very fast and very encouraging. And we're seeing the patient funnel now starting to shape - take shape in the United States.

So, I've been describing the patient funnel over the last year in Germany and the US patient population is substantially larger than that of Germany.

But early signals in the US look like the taking shape of that patient funnel is going to have some similarities to what we've experienced in the United States, all of which gives me a great deal of confidence that as we finish up this year, hopefully, treat some patients in Q4, that we're really set up with payer approvals in Italy and Germany and the dynamics in the United States falling into place, all of which point to greater uptake in 2024.

Thanks for the question..

Your next question comes from the line of Geoff Meacham of Bank of America. Your line is open..

Great. Hey, guys. Thanks for the question. JJ also wanted to offer up congrats on the retirement. So, not surprisingly, I have a few on ROCTAVIAN as well.

So, the first one is, I know you're not giving more detailed '24 guidance than the $3 billion in revenue, but at a high level, how would you characterize the ROCTAVIAN contribution? And the second question is, I guess when you use German - Germany as a proxy, you have 60 patients that are pretty late in the on-boarding process.

It's been on the market officially for over a year. Is there – is there what you characterize that as a second wave or is the 60 mostly hit? I wasn't sure kind of if there's a bit of a ripple effect once you get formal reimbursement? Thank you..

Hey, Geoff, Brian here. I'll start with first question. On the $3 billion, as you noted, haven't given the specifics behind that. We'll plan on doing that early next year like we typically would. But importantly, there's both continued growth in VOXZOGO over '23 and a meaningful contribution from ROKTAVIAN.

So, I'll ask you to stay tuned for the details, but you understand what has been the typical growth trajectory for the mature enzyme products. Still growing healthily here, plus substantial growth in VOXZOGO, plus meaningful ROCTAVIAN contribution gets us to that approximately or approaching $3 billion..

As usual, we will give more detailed guidance when we report to Q4 in February of next year..

And I think great question about the 60 AAV5 by the eligible patients that have yet to be treated in Germany. Actually, the pace of CDX testing in Germany has slowed down over the summer.

That's probably a reflection both of the general slowdown in August in particular in Germany and also a reflection that, as I noted previously, our earlier plan to treat patients in the free pricing period while we were negotiating with GKV wasn't paying out the way we had hoped it would.

So, we know the HTCs were slowing down in Germany waiting for the GKV process to be finished.

My perception is a pickup following the end of the summer in CDX activity and lining up patients to be treated in Germany is both reflective of, one, getting past the summer and, two, an expectation that these HTCs know essentially that we've come to conclusion on price.

They're just waiting for that price to be published so they can move ahead with patient treatment. And while we're on the subject of Germany, which the physicians in Germany and the data on other launches would bear out, Germany moves slow for adoption of new hemophilia options.

Having 60 patients in Germany that are AAV5 eligible on a population-adjusted basis in the United States would equate to about 240 to 250 patients. So, just benchmarking what may be the possibilities in the US. Thank you..

Your next question comes from the line of Phil Nadeau of TD Cowen. Your line is open..

Good evening. Thanks for taking our questions. JJ, let me add our congratulations on a very successful tenure and your retirement from BioMarin. Again, a couple of follow-ups on ROCTAVIAN, specifically on patient demand.

On the last earnings call, you mentioned that patient consent forms had been trending well and BioMarin was happy with the rate that they had started to come in. Any update on how patient consent forms are trending, and is there any visibility on when the first US patients could be treated? That's question one.

And then question two, in terms of the institutional challenges, we've had some physicians mention things like training staff, beds need to be set up, equipment needs to be ordered. Are those challenges at the HTCs, and if so, is there anything BioMarin can do to remove those bottlenecks? Thanks..

Thank you for the question, Phil. So, let me start with the second point first, the institutional challenges. In the prepared remarks, I addressed HTC site readiness and some of the elements of that that I think are one-time events that won't be recurring.

The types of things that you just mentioned, I would say, generally are captured in that HTC site readiness and some of the institutional things that they're doing to get ready for ROCTAVIAN treatment in particular, and taking a little bit of time, which should be resolved and facilitate patients to move expeditiously through those types of things going forward.

In terms of patient demand in the United States, we're not disclosing patient level detail in the United States, but we're continuing to see, as I noted, that patient funnel build-up in the US, and I'm qualitatively encouraged by what we're seeing so far.

In the US, we have this hub operation, and in prior launches, all of the patients move through our hub essentially first before they move through the next steps towards treatment.

Given the nature of the HTCs and their capabilities, and the fact that they operate in this multi-sponsor environment, we've been seeing patients come into our hub maybe later in the process and not at the very beginning of the process. So, this is a little bit of a different dynamic for us.

We're getting our hands around that one, but yes, encouraged by the patient demand that we're seeing in the United States and the patient funnel building up..

Yeah, in addition to the federal building up, though, I mean, it is possible, I think that was your question, can we treat some US patients by year end [ph] I would say, yes, it is possible. We have three US patients who have now cleared all ROCTAVIAN screens for treatment, like the AB5, liver scan, liver health, and all that.

So, the timing of their treatment isn't guaranteed in '23, but they have completed all eligibility testing for treatment, so it will very likely occur in the not too distant future..

Your next question comes from the line of Robyn Karnauskas of Truist. Your line is open..

Great. I have three quick questions. Number one, JJ, you have mentored so many people on the street, so appreciative. Is Hank retiring too, because we will have a panic attack, so like, would you like an announcement on that call? Is Tracy getting a promotion? That's our first question.

The second question would be, ROCTAVIAN, there was such a focus, and you misguided this year on the outcome of what you could achieve. Do you think in 2024 you can do better? And then I think on VOXZOGO, I mean, that came away from our analyst meeting as like the big takeaway.

So, how do you think about letting analysts understand the opportunity there and the timelines for that? And I'll go back to Tracy's promotion. Is Hank leaving? I'll leave it at that..

Thank you, Robyn. I mean, I think there was a previous question from, I think, from Salveen, and we had a detailed answer from an analyst from Geoff. Indeed, it's taken longer than we anticipated to get the - to connect the patient with the treatment centers, to get the whole system wired.

So, again, big picture, when you have such a big ticket item like ROCTAVIAN, $3 million, whack, it attracts a lot of people. So, essentially, it's a big pie that attracts a lot of players that you don't get involved in the decision-making because they all kind of want a piece of the action. Just so Jeff mentioned the 340B.

340B is 20, I mean, all basically, all hemophilia patients in the US, statutory-wise, are 340B patients. When you're talking 20%, 340B discount with $3 million whack drug, you're talking about $600,000. As you can understand, many people get interested in that pie and want a slice of it, which just slows things down.

But eventually, long-term, it's actually good news that it will be taken care of. So, the fact that the takeoff has been delayed, to me and to us at BioMarin has no impact on the future potential of these drugs. It's taking longer than planned.

It took longer - I'm sorry, when the first time we got a product approved in Europe before the US, and ROCTAVIAN got approved in Germany, and based on our previous experiences, you know, we thought we could be able to treat some patients during the free pricing period in Germany, which is slowly disappearing, didn't happen.

Then we are basically, you know, very, very close to a final deal with the German authorities, which generally takes about 12 to 13 months. So, in this respect, we're not that far behind versus the European approval. So, again, we believe ROCTAVIAN has great potential. We believe ROCTAVIAN would be a significant contributor in 2024 and beyond.

Obviously, not as much as VOXZOGO, which is turning into a very, very large drug based on our Q3 results, not to say Q4, and the fact that, thanks to the efforts of our drug supply team, all the constraints in terms of packaging that we had and sealed finish that we had this year are starting to go away and will be much more substantial.

We have much more substantial capacity in Q1 and Q2, and then be free of all capacity constraints by the middle of the year. So, I hope that answers your question, and I'll get back to you regarding Tracy..

Your next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is open..

Great. Thanks very much, and best wishes to JJ. That's really the end of an era.

So, I guess I was wondering if you can help us understand what kinds of initiatives you've undertaken to address the administrative delays and site readiness issues, and, you know, what kinds of success have you had where you have implemented these things, and what initiatives do you have left to implement still to support ROCTAVIAN's growth? Any more color there would be very helpful..

Thanks, Joe, for your question.

I would characterize the answer to that as less specific initiatives and more just, you know, the nuts and bolts and mechanics of selling, of providing scientific support to HTCs, the physicians, patient advocacy groups, including local chapter events, all the things that help them through those little steps and lots of little decisions, including the big decision of affirmatively making the decision to treat.

And as Hank and I have discussed just this week, we're really focused on those small tactical, on the ground elements with our teams to just keep those things moving through the various little challenges that are popping up.

So, it's more about dealing with those little things, getting to the other side of them, many of which are one-time events, and less about introducing new initiatives..

Thank you..

And if I may ask you, regarding Germany, again, in Europe, you know, patients don't pay for drugs. They don't pay either for doctor's visits, so they don't know the price of a drug. But what, so, the key thing in Europe is to have official government reimbursement for your drug. That's about to happen in Germany and Italy.

We basically, as we've said, we have an agreement on the price in Germany already. Now we need to have this price published, which should occur over the next few weeks. Once that happens, there is no barrier whatsoever left, you know, in Germany, because 60 patients are 85 negative in Germany.

It's very likely that the vast majority of them will be treated. Obviously, most of them next year, because there are so few weeks left in the year because of the holiday season is coming up, you know, pretty soon, and the fact that the price probably won't be published for another, three or four weeks..

Your next question comes from the line of Chris Raymond of Piper Sandler. Your line is open..

Thanks, and congrats from us, too, to JJ, and sorry to see you leave, JJ, and really enjoyed working with you all these years. I've got two questions, maybe one a commercial one, maybe for Jeff, and then one for Hank, if that's okay.

So, maybe just on VOXZOGO, Jeff, just on that supply constraint issue, maybe could you talk a little bit about the triage process that you've instituted with new patient starts? I guess, I'm just kind of wondering what kind of retention programs do you have in place for those new patients who want to be on therapy but can't.

And can you give us a sense of that number now, and where you expect it to grow to, you know, when you get back up to supply mid-next year and start to treat those patients? And then, maybe on the R&D side, Hank, just noticing back at your R&D day, which was just in September, I think your cardiomyopathy programs, I think 293 was supposed to have its initial data proof of concept in 2025, and I think 365 was the year after.

It looks like those have been pushed a year. It's only been a few weeks since your R&D day. Maybe, is there a sense of what's happening there? Thanks..

Thanks, Chris. So, let's start with the VOXZOGO supply constraint issue, and I'll ask Greg and Brian to jump in if they think I'm missing any here.

But qualitatively, what I can tell you is by the time we were looking at our patient demand and the resulting unit demand forecast, the very beginning of this year, we anticipated that we would be getting to a point during the course of 2023 that we would not be able to satisfy all of the patient demand that we saw springing up in all of our commercial footprint.

A reminder that we're active now in 38 markets. So, our objective was two-fold during the course of the year.

The first was to ensure or do our best to ensure that if we were starting patients on VOXZOGO therapy in any of those markets, that we could assure the supply continuity behind those specific patients, and that we would minimize or eliminate the risk that patients starting therapy would have to go off therapy for either a very short or a prolonged time, which required a lot of forward planning.

And a reminder, you hear a lot about the different dynamics of markets. You know, the different markets look very different. So, having, you know, a 38 market footprint to be projecting into, projecting those patient demands, looking at our labeled product supply, going out, six and nine months forward was a pretty dynamic situation to manage.

But getting on top of that early, allowed us to say in certain markets, we're going to delay our entry into that market because we can't be assured of keeping patients on therapy once we start them, but also having a forward looking date that we'd be able to communicate and say, look, if we can't get into this market on, May of this year, for example, with an increasing supply, still supply constrained, but supply increasing, when could we project that market to come online for patients to be treated.

Those are the kind of dynamics that we were working through. And as you can – as you can tell by the different quarterly results and our remarks during the year, we've now kind of reached that point where there are patients in certain markets that we are attempting to not get started on therapy because we can't guarantee supply.

And there are markets that we have earmarked for the future to open up and begin treating patients because we couldn't guarantee the continuity of supply for earlier starts. Maybe I'll pause there and look at Brian or Greg for additional comments..

Yeah, Chris, this is Greg. I'll just add. So the way you should think about it and Jeff stated it, for the end of the, to the fourth quarter, we kind of – we'll add 300 new patients, as you said. What you have to think about is we have done a lot of work since we were last on a call with you. And first quarter is less constrained.

Second quarter is almost close to not constrained. And by mid-year, we'll have no constraints. So it is – it is getting better by the day. So it's not like some event happens in mid-year. It gets us to totally unconstrained. We're going to be building inventory and building supply and able to support more and more of those patients.

There is a significant uplift in patients in the in the first half of next year that we'll be able to support. And then by mid-year, we'll be fully unconstrained for all those markets, all those patients.

So think of it as a taper over time that we will start to go after those patients, as opposed to some event that will consume all those patients in mid-year, if that helps..

And then Chris, I just want to address your question about certain earlier stage programs shifting. They haven't. As part of our ongoing efforts to streamline communications, we're going to be updating the street when we have clinical proof of concept.

So those dates, just the points in time when we're communicating updates have changed, but none of the actual advances have changed. So the next question..

Your next question comes from line of Paul Matteis of Stifel. Your line is open..

Great. Thanks so much. And I'll add my congrats to JJ as well. Appreciate the question.

I was curious, when you were undertaking the CEO search and succession planning over the past couple years, what were the two to three key things that you were prioritizing? And as you were thinking on selecting new leadership, how important was it that a new CEO would really stay the course in Biomarin's core strategy over the past few years? Or I guess what I'm kind of trying to say is as we think forward, what are the chances here that Alexander Hardy does actually enact material changes over the next 6 months to 12 months and Biomarin in certain ways could look differently? Thanks so much..

Yes. So let me try to answer your question. So we've done a pretty comprehensive search, mainly over the past year or so that accelerated about a few months ago. And we had several very good candidates, but the Board thought that Alexander was probably the best candidate. As you know, he served as CEO of Genentech since 2019.

Over there, he was responsible for the company's $25 billion a year business and leading 13,500 employees. So we believe that he has demonstrated the ability to deliver growth, which is what continues to be needed at Biomarin.

He steered Genentech through the loss of exclusivity of three major drugs during that time that together accounted for 40% of the company's revenues in 2019. And he returned the portfolio to strong growth by the end of 2022. So we believe that he has the ability to continue to grow our commercial business pretty successfully.

We understand from reference checks that he's a very good leader. And he's been evolving and working in competitive markets, of course, a range of therapeutic areas, including hemophilia, as you might have noticed. And he's overseen the launch of 10 new molecular entities during his time as CEO of Genentech.

So he has a strong background and understanding in drug development and science. So, Alexander hasn't been hard to make some major changes within Biomarin. He's going to assess the situation and will determine what needs to be changed, if anything. But I think we all look forward to working with Alexander..

Your next question comes from the line of Akash Tewari of Jefferies. Your line is open..

Hi, thanks for taking our questions. This is Ivy for Akash. And JJ, congrats on the retirement.

The former question, so I guess for 2024, I know you haven't given any product specific details for - what will be the cadence of new patients add next year for both US and ex-US, because consumers right now has 350 million contribution from ROCTAVIAN, which looks quite high compared to the below 10 guidance you have for this year.

So what do you think needs to happen to hit that target? Or is that like a fair target to say? And secondly, I think it's for your mid-decade rev go off around $4 billion to $5 billion.

Are there any updated thoughts to that target? And if you are to breakdown this $5 billion by product, how much of it is from VOXZOGO? And how much of it is from ROCTAVIAN? Thanks..

I'll start with the big picture, revenue questions. This is Brian then Jeff can maybe touch on the cadence briefly. So I touched on this a little bit in Jeff's question earlier. The key take away from the approaching $3 billion revenue expectation for 2024 is that ROCTAVIAN is expected to come online globally, mostly Germany and US.

And the challenges and delays that we've discussed for 2023 in the context of 2024, we expect to be timing. Jeff and JJ touched on the German price dynamics. We've got the patient funnel filling up with what we believe to be the final gate, which is concluding the price and getting the publication in the National Register.

That should open up that pool of patients for 2024. In the US, Jeff on a couple of the answers has talked about these dynamics that are coming together, positive momentum. But that's why we use the terminology network to bring all those pieces together.

Patient, physician interest, site readiness, contracting, and reimbursement, they all need to come together to have patients come online. That's taken longer in 2023, but we expect to be making significant progress over the next few months where we'll start to see those patients come online in '24.

So the key take away from that $3 billion is that there is a meaningful piece of ROCTAVIAN there, which is a bridge from where we're at in '23. And then briefly, no changes to the $4 billion to $5 billion, obviously, we need to continue to monitor and execute on both VOXZOGO and ROCTAVIAN.

We've commented previously that that $4 billion to $5 billion is roughly made up of half of the base business with continued growth and half of ROCTAVIAN and VOXZOGO..

But I think we refer you to some comments - answers to questions that we had previously on the call that should address your questions, because they were asked earlier. Sorry, we're running out of time..

Your next question comes from Jessica Fye of JPMorgan. Your line is open..

Hey, guys. Thanks for taking my question, and JJ best wishes for your retirement.

Recognizing what you're doing to manage supply with VOXZOGO, can you just talk qualitatively about the geographic mix of VOXZOGO sales, and which regions or countries have the most growth left in front of them in achondroplasia?.

Yeah, I don't think that we're disclosing market level detail, Jess, but overall mentioned that there were 12% patient penetrated of the indicated patient population, which includes the four months and up in Europe and from birth, essentially, in the United States. There is some variability in uptake.

I think I mentioned previously that early rapid uptake in places like Germany and Japan leave them at a relatively higher penetration rate, so far without ceilings, but a higher rate in other places, importantly, like the United States, which just had a huge expansion of the patient population open to us.

That patient population, very young patients having the strongest value proposition for treatment opens up a lot of penetration room in the United States, for example, probably too much detail to get into for other markets..

And your last question comes from the line of Ellie Merle of UBS. Your line is open..

Hey, guys. Thanks so much for squeezing me in.

Just in terms of the VOXZOGO expansion studies, from a disease biology perspective, how should we think about the potential mechanistically for CNP to expand into other indications relative to FGFR inhibitors? I guess, are there indications where you think the biology might make more sense for CNP and not FGFR or vice versa, or where you think CNP is particularly likely to be active? Thanks..

Blessings on you, Ellie, for asking the question, so that I could both say unequivocally to Robin's earlier question, I'm here and very committed to BioMarin.

And partly for exactly this reason, I think that when you look at the genetics of statural impairments, and our group has actually published quite nicely on this, that gain-of-function mutations in CNP confer a high benefit, loss-of-function mutations, convey short stature across a polygenic background.

That, I think, is very strong evidence that CNP is going to be a dominant regulator of bone growth. Interestingly, you can find loss of function or - sorry, gain of function variants in FGFR3 when they are associated with stature. They're also associated with profound other abnormalities.

So that's why we think that the CNP axis is going to be the perfect target for improving stature across a wide range of both genetic and polygenic indications, and why FGFR3 approaches are primarily going to be limited to FGFR3 abnormalities. You can get a lot of height benefit nudging the CNP axis safely.

You have to hit the FGF axis quite hard in non-FGF indications and probably too toxic effect. At least that's based on human genetic data. So thanks for the question. We're very excited about that future..

There are no further questions at this time. I'll now turn the call over to JJ Bienaime, Chairman and CEO..

Thank you, operator, and thank you all for joining us today. We are pleased with our results this quarter and our prospects ahead. BioMarin is now a profitable, fully integrated industry leader with annual revenues well over $2 billion and is extremely well positioned for substantial future growth and profitability.

Thank you for your continued support and have a good afternoon or evening..

This concludes today's conference call. You may now disconnect..