Please note, this event is being recorded. Thank you. I will now turn the call over to Tram Bui, Halozyme's Vice President of Investor Relations and Corporate Communications. Please go ahead.
Thank you, Operator. Good morning and Happy New Year, everyone. Welcome to our investor conference call. In addition to the press release issued today before the market open, you could find a supplementary slide presentation that will be referenced during today's call in the investor relations section of our website. Leading the call will be Dr. Helen Torley, Halozyme's President and Chief Executive Officer. We also have Nicole LaBrosse, our Chief Financial Officer, on the call. Please note that we will be making forward-looking statements as outlined on slide two. I would also refer you to our SEC filings for a full list of risks and uncertainties. During the call, both GAAP and non-GAAP financial measures will be discussed. Certain non-GAAP or adjusted financial measures are reconciled with the comparable GAAP financial measures in our press release and slide presentation. I will now turn the call over to Dr. Helen Torley.
Thank you, Tram. Good morning, everybody. Today, I am pleased to provide our financial guidance for 2025. We will also provide an update on our 2026 - 2028 projections. In providing color on the revenue drivers, we will be focusing on the nine approved ENHANZE products, plus amivantamab exclusively, and our broader product portfolio will be discussed at our fourth quarter and full year 2024 financial results call in February. Over the last decade, we have built a high-growth and durable business with our leading ENHANZE drug delivery technology platform and extended our opportunity with our innovative autoinjector technology platform and commercial products. Through our operational expertise, we have now advised and supported our partners to achieve nine global regulatory approvals and launches for ENHANZE co-formulated products.
During this journey, we achieved an unsurpassed safety record and unyielding demonstration of market acceptance and commercial success for ENHANZE, which has resulted in Halozyme's track record of strong revenue and earnings growth. 2024 represented another year of outperformance for Halozyme. We raised guidance twice during the year. This was driven by the growth of DARZALEX subcutaneous and PHESGO, which exceeded our expectations, and by the impact of new intellectual property granted in Europe, which extended ENHANZE intellectual property to 2029 and maintained the royalty rate for DARZALEX subcutaneous at the mid-single-digit rate. Today, as a result of this strong momentum, we are pleased to provide our 2025 guidance, which is meaningfully higher than we presented a year ago. Moving now to slide three, we are reiterating our 2024 guidance that we raised for the second time when we reported our third quarter results.
This is shown on the far left column. For 2025, we are raising our financial guidance for total revenue, for our high-margin royalty revenue, for Adjusted EBITDA, and for non-GAAP diluted earnings per share, which are all increased from the guidance we provided last year. Beginning with total revenue, we project year-over-year growth of between 16% and 23% to $1.15-$1.225 billion. This is largely driven by royalty revenues, which are projected to be $725 million-$750 million, a projected increase of greater than $175 million year-on-year, and representing 30%-35% growth. I will note that these projections are based on input received from our partners. For the first time, argenx's VYVGART Hytrulo with ENHANZE is projected to be the largest royalty dollar growth driver. We are also projecting that DARZALEX subcutaneous and PHESGO will continue to grow substantially in 2025.
Adjusted EBITDA guidance is $755 million-$805 million, an increase of more than $160 million year-over-year, and representing growth of 24%-32%. This strong performance is a result of our robust revenue growth, and in particular, the high-margin royalty revenue growth, coupled with the flat operating expense resulting from our continued execution on operational efficiency. Non-GAAP diluted earnings per share is expected to increase 21%-30% to $4.95-$5.35. As Nicole will review in a moment, this strong momentum is also resulting in a meaningful increase to each year of our multi-year guidance to 2028. Let me now provide some details on the multiple de-risk 2025 catalysts that are driving this remarkable performance shown on slide four. On the left, you see VYVGART Hytrulo, which was approved for the treatment of generalized myasthenia gravis in the U.S. and in Europe in 2023.
For any new product launch, we assume it will take six to nine months in the United States and more than 12 months in Europe to achieve robust access, coverage, and reimbursement. With strong access for gMG achieved in 2024, we are reaping the benefits in 2025 with robust growth projected in generalized myasthenia gravis. As noted in the middle panel, in 2024, we gained four additional global product approvals. These will follow the same initial uptake trajectory resulting from the timeline to achieve robust access, coverage, and reimbursement. As our partners focus on gaining and expanding coverage, access, and reimbursement in 2025, we project modest contributions from VYVGART Hytrulo in CIDP in the United States to TECENTRIQ HYBREZZA with ENHANZE, OCREVUS ZUNOVO with ENHANZE, and late in the year from OPDIVO Qvantig with ENHANZE this year. Contribution will then grow meaningfully in 2026 and beyond.
We truly are seeing the impact of the breadth of our portfolio and the remarkable partner products we collaborate on. Moving now to slide five, I will provide some additional color on argenx's VYVGART and VYVGART Hytrulo with ENHANZE. Approved now in generalized myasthenia gravis in the U.S. and Europe, and with CIDP recently approved in the U.S. and Japan, total VYVGART and VYVGART Hytrulo sales are projected by analysts to be $1.8 billion in 2024, growing to almost $5 billion in 2028, with analysts projecting generalized myasthenia gravis contributing 60% of sales and CIDP 40% of sales in 2028. Recall that only VYVGART Hytrulo with ENHANZE, the subcutaneous version, is approved for CIDP. The approval and launch of VYVGART Hytrulo with ENHANZE provided the option for patients to receive their treatment with a 30-90-second subcutaneous injection rather than a 60-minute IV infusion.
argenx has commented that the availability of VYVGART Hytrulo has resulted in an expansion in the number of prescribers and new-to-VYVGART treatment starts, each of which is contributing to the accelerated growth that has occurred. With broad reimbursement and access in place in the U.S. and Europe for gMG, and growing in CIDP in the United States, and with the recent Japan approval in CIDP and potential launch of CIDP in Europe in 2025, we project continued expansion of uptake and use by prescribers. As a result of this growing market demand in the first two indications and the mid-single-digit royalty and net sales that Halozyme receives until 2033, VYVGART Hytrulo is projected to be our largest royalty dollar growth driver in 2025 and to contribute meaningfully for many years, and this is really just the beginning for VYVGART and VYVGART Hytrulo with ENHANZE.
argenx describes their strategy as a pipeline and a product, and as shown in slide six, there are already multiple new indications in development with VYVGART Hytrulo subcutaneous, with the potential to further add to and expand the TAM and opportunity. VYVGART Hytrulo has the potential to truly transform the treatment and outcomes for patients with a broad range of serious autoimmune diseases, just as DARZALEX has done for multiple myeloma and amyloidosis. Let me now move to DARZALEX on slide seven. DARZALEX subcutaneous with ENHANZE continues its remarkable growth journey. Analysts project 2024 revenue of $11.6 billion, a robust 20% growth on an already high base 10 years after the initial IV launch.
With a 95% share of sales in the U.S. now for DARZALEX subcutaneous with ENHANZE and similar high numbers outside the U.S., it is the subcutaneous version with ENHANZE that, by enabling deeper penetration into front and second-line treatment populations, is creating this robust growth. Further fueling opportunity and growth, J&J recently reported impressive new DARZALEX subcutaneous with ENHANZE data in a new population of smoldering myeloma, further expanding the TAM for DARZALEX subcutaneous upon regulatory approval and launch. Projecting forward, analysts expect continued strong year-over-year growth over the next few years, resulting in greater than $17 billion in sales in 2028. Recalling that 95% of sales in the U.S. is in subcutaneous with ENHANZE and that Halozyme receives on average a mid-single-digit royalty and net sales until ENHANZE LOE, you can see why DARZALEX will remain a key growth driver for Halozyme for many years to come.
DARZALEX subcutaneous is clearly established as the backbone of multiple myeloma treatment, beginning in front line and continuing to second line and later. This did not occur by chance. J&J has invested in the most robust and expansive clinical evidence generation program, and as a result, DARZALEX subcutaneous has established a benefit-risk profile that is, in my view, extremely hard to match. PHESGO is shown on slide eight. PHESGO is Roche's fixed combination of HERCEPTIN, PERJETA, and ENHANZE, delivered subcutaneously to patients with breast cancer in just minutes. This is a product that I think does not get enough attention. Analysts project sales of $1.9 billion in 2024, growing to $3.4 billion in 2028. These sales are all subcutaneous with ENHANZE, meaning that Halozyme will receive a mid-single-digit royalty on the total net sales, and these are projected to continue until 2030.
Summarizing this total opportunity, our two 2020 launch products, DARZALEX subcutaneous and PHESGO, represent $20 billion in IV and subcutaneous sales in 2028. Continuing on our current and near-term de-risk growth catalysts included on slide nine are the three recently approved products that will add to and further drive revenue diversification in the next years. As our partners focus on gaining and expanding coverage, access, and reimbursement in 2025, we project modest contributions from these products this year. Contributions will then grow meaningfully in 2026 and beyond. Total IV and subcutaneous sales of these three products are projected to be approximately $25 billion in 2028, adding to the $5 billion projected IV and subcutaneous sales from VYVGART, and representing an approximately $30 billion potential opportunity, an even greater opportunity than we project for DARZALEX subcutaneous and PHESGO. Let me begin with OCREVUS ZUNOVO.
I commented earlier that the availability of subcutaneous with ENHANZE can expand the market opportunity, as demonstrated by DARZALEX subcutaneous and VYVGART Hytrulo. This is exactly what Roche plans with OCREVUS ZUNOVO, stating that the availability of subcutaneous OCREVUS is projected to add approximately $2.2 billion in sales on top of the already multi-blockbuster sales of OCREVUS IV, which are projected to be approximately $8 billion in 2024. This expansion is the result of new prescribers who do not have the infrastructure of IV treatment and have not prescribed OCREVUS IV, now prescribing OCREVUS ZUNOVO. There will also be projected IV conversion driven by the dramatically shorter treatment time of just 10 minutes compared to the multiple hours required for the IV. Of note, patients reported a 92% satisfaction rate with OCREVUS ZUNOVO.
We are also excited regarding Roche's TECENTRIQ HYBREZZA and our most recently approved product with ENHANZE, OPDIVO Qvantig. In each case, the patient now has the potential to receive their treatment subcutaneously in just minutes. BMS's CEO, Chris Boerner, has commented that BMS aims to convert 30%-40% of the current Opdivo business to subcutaneous. With Opdivo sales projected at $10 billion in 2028, this represents another exciting royalty revenue stream driving our revenue growth. Moving to slide 10, with the recent FDA approval of Bristol's OPDIVO Qvantig with ENHANZE, we now have nine de-risk approved products on the market, providing more flexible treatment options to patients across oncology, immunology, and neurology. These nine products, plus J&J's amivantamab, are the drivers of our projections to deliver $1 billion in royalty revenue in 2027.
I was recently reflecting that I first provided this guidance of $1 billion in royalty revenue in 2027 in January of 2018 at the JP Morgan Conference, a remarkable seven years ago. With our royalty revenues projected at $725 million-$750 million this year, I'm pleased to say that after delivering each year on our royalty projections, we are clearly strongly on track to deliver greater than $1 billion with a projected $1.1 billion-$1.15 billion in royalty revenue in 2027. With that, let me now turn the call over to Nicole.
Thank you, Helen. Seen here on slide 11 are estimated results for 2024, consistent with our previous guidance ranges. Recall that these expected results are after two guidance raises throughout the year, and we expect to achieve approximately $1 billion in revenue in 2024.
These are preliminary estimates, and final results for 2024 will be reported on our February earnings call. Growth rates on this page are calculated from the midpoint of the 2024 ranges. I will now move to our guidance for 2025 and then provide an update to our 2026 - 2028 outlook, where all periods are raised from our previous outlook. In 2025, we project another record year, reaching new heights with increased projections of $1 billion and $150 million to $1 billion and $225 million in total revenue, growing 16% - 23% year-over-year. This continued revenue growth is driven by royalty revenue, which represents greater than 60% of total revenue in 2025.
As Helen mentioned, VYVGART Hytrulo SC is projected to be the largest driver of dollar growth, in addition to continued growth from DARZALEX SC and PHESGO, in contribution from the recently launched OCREVUS ZUNOVO, TECENTRIQ HYBREZZA, and OPDIVO Qvantig. For modeling 2025 on a quarterly cadence, our partnered product sales and collaboration revenues are expected to be substantially weighted in the second half of 2025. We anticipate the first quarter of 2025 royalties to be flat relative to the fourth quarter of 2024 due to annual contractual rate resets. We project total revenues to decrease sequentially from the fourth quarter of 2024 to the first quarter of 2025, as there are no milestones planned in the first quarter, with quarterly growth sequentially thereafter. Our high-margin revenue mix translates to Adjusted EBITDA expansion, growing year-over-year by 24%-32%.
This continued strong EBITDA allows us to continue to return capital to shareholders, and I'm happy to announce that we recently entered into a new $250 million accelerated share repurchase program. Our ability to execute share repurchases is due to our strong free cash flows, which is projected to represent approximately 75% of Adjusted EBITDA in 2024, or $445 million-$470 million. Our low net leverage profile of an expected 1.4 times at year-end, coupled with our impressive interest rate coverage ratio of 30 times, nicely establishes our capital position to execute on both share repurchases and growth opportunities via M&A. Strong Adjusted EBITDA growth, when coupled with our recent share repurchase activity, results in accelerated non-GAAP EPS growth of 21%-30%.
This strong growth trajectory sets us on a clear growth path for many years to come, and it provides us with the conviction to increase our previously provided projections for 2026 through 2028. Before I dive in deeper, let me highlight on slide 12 the remarkable growth that we project over the next four years. From 2024 - 2028, we project royalty revenue, Adjusted EBITDA, and non-GAAP EPS will more than double, while total revenue comes close to doubling, increasing from approximately $1 billion to a range of $1.7 billion-$1.9 billion, and this is 10 years after our first enhanced partner product launch. Moving now to slide 13 for more details. Please note that growth rates for our long-term view are calculated from midpoint to midpoint of the ranges. Beginning with total revenue, we have raised our expectations for 2025 to 2028.
We project continued strong year-over-year growth of 25% in 2026 and 16% in 2027. This growth is largely driven by increasing royalty contribution, resulting in a projected royalty revenue growth of 25% in 2026 and 22% in 2027. We are excited to share an updated view on 2028 revenue, which continues to project a preservation of royalty revenue and total revenue, even while accounting for the potential step-down in DARZALEX FASPRO U.S. royalties beginning in September of 2027. This is a result of the continued revenue growth of recently launched products, offsetting the impact of the currently projected U.S. DARZALEX SC royalty rate step-down.
Recall that a new patent underlying the preservation of the DARZALEX SC royalty rate in Europe is expected to be granted for a similar claim in the U.S., with the same impact of extending the time of full royalty rates to March of 2029. The impact from the potential IP issuance in the U.S. would be additive to our guidance ranges. What's most exciting about our royalty projections is that these projections include the nine products that are currently approved with ENHANZE, and one additional product, amivantamab SC, which is projected to be approved. The impact from potential new indications for VYVGART Hytrulo, new product launches, and new licensing opportunities would be additive to the growth seen here. You can see on Slide 14 that the impact to the bottom line is meaningful. We project annual growth in Adjusted EBITDA of 33% in 2026 and 22% in 2027.
Similar growth rates are seen in non-GAAP EPS, which only includes the impact of the recently initiated $250 million share repurchases through an ASR, and the potential benefit of additional share repurchases as part of our 2024 approved $750 million share repurchase program are not reflected. On slide 15, we have provided more details on the revenue categories, and I'll also discuss the five-year CAGRs, and we'll highlight what I find most impressive about our projections. Firstly, we continue to project strong revenue growth from our predictable royalty streams, growing from $448 million in 2023, with a projected five-year CAGR of 21%. Secondly, total product sales are growing throughout the period while achieving our goal of being the cost leader for API.
Our rHuPH20 API sales are projected to grow only modestly over this horizon, reflecting the impact of efficiency improvements to reduce costs that we pass on to our partners as a source of competitive advantage. The growth we see in product sales is achieved as a result of the high growth rate for XYOSTED. We continue to see strong contribution from collaboration revenue, driven by our partners achieving development and commercial milestones. Thirdly, and as a result, total revenue is projected to achieve greater than $1.7 billion by 2028, with a 2023-2028 CAGR of 17%. Lastly, and importantly, I'll focus you on our Adjusted EBITDA. You will note that Adjusted EBITDA is growing faster than revenue in every year of the five-year outlook, with a 2023-2028 CAGR of 26%.
This is a result of expansion of the contribution of our revenue mix, largely driven by increasing royalties. Each dollar of royalty revenue drops almost entirely to the bottom line, resulting in Adjusted EBITDA margin expansion from 51% in 2023 to approaching 75% in 2028. This, coupled with our business model and ability to keep our expenses relatively flat, creates the higher rate of growth for EBITDA. Moving to slide 16, growing and predictable EBITDA significantly de-risks our capital position, as we have ample capacity to cover our debt obligations without overextending our resources. Any leverage we would take on has the certainty to be swiftly reduced, putting us in a strong capital position. We demonstrated this following the Antares acquisition, deleveraging by almost two turns within two years, all driven by EBITDA growth, while concurrently returning $850 million in capital through share repurchases over the same horizon.
This was accomplished with less than half of the starting revenue base we have today. In 2024, we estimate free cash flows of $445-$470 million, representing approximately 75% of EBITDA. We project free cash flows of $575 million-$610 million in 2025, or approximately 76% of EBITDA, and growing to $795 million-$865 million, or approximately 80% of EBITDA in 2026, driven by increased royalty growth. Just imagine the potential to put free cash flows to work, driving value for shareholders. I think you will agree that the EBITDA amounts and free cash flow are impressive, and this is what will allow us to allocate capital to drive further growth. With that, I'll now turn the call back over to Helen.
Thank you, Nicole. As you've just heard, 2025 will be another year of strong revenue and earnings growth for Halozyme.
The 2023 and 2024 approvals and launches are powerful growth catalysts for 2025, 2026, and beyond, as evidenced by our updated multi-year guidance for many years to come. With that, Operator, we're happy to open the call for questions.
We are now opening the floor for question and answer session. If you'd like to ask a question, please press star followed by one on your telephone keypad. Your first question comes from Brendan Smith from TD Cowen. Your line is now open.
Hi, happy New Year, and congrats on the update. Really great to see. Thanks for taking the question. Maybe just a couple of quick ones from us. Helen, first, I wanted to ask about some of these new launches. You mentioned the six to nine months in the U.S a nd maybe 12 months in the EU, I think is what you said, really to get some of these up and running. You know, Roche has also said that for the OCREVUS subQ, you know, they're expecting that getting into the new non-IV infusion centers would be key to really maximizing the opportunity there.
So just wondering if for that drug we should expect it might take even longer than the six months, or if that IV to subQ conversion could maybe help make up the difference there. Really just trying to see how we should look at the cadence of uptake for that. Then just really quickly, we obviously saw some great combo data this week with the Rybrevant/Lazcluze compared to Tagrisso. So just wondering how that update might have changed the way you and J&J are seeing that opportunity, and maybe by how much more you think subQ could see growth there if it really winds up beating Tagrisso in that setting? Thanks very much.
That's great, Brendan. With OCREVUS, I do think at launch, where Roche has certainly in their comments suggested they're having the representatives focus initially, is on getting new prescribers. And so as we think about the U.S., I think six to nine months is still a good estimate as to when reimbursement will be in place and a good estimate of the time it would take to encourage new prescribers to be ready to use the subQ.
Certainly, I think the six to nine months and 12 plus months for Europe takes into account that educational element that will happen on new prescribers, even as current prescribers, and we mentioned this in the prepared remarks, will be contemplating conversion of some of the IV just based on the much shorter treatment times that'll be available with the subQ versus the IV. With regard to amivantamab, yes, incredibly exciting data yesterday. We were delighted to see that. You know, there's always been a comment on J&J's calls that there's a disconnect between how analysts have been projecting amivantamab and how J&J has been considering it. And the CEO of J&J has always talked about AMI being a $4 billion-$5 billion brand.
I think that the data we're seeing yesterday are really a reflection of their conviction that that data would be positive, and that is what's driving towards the $5 billion, being able to beat the stalwart like Tagrisso in this marketplace. So I do think this will allow that disconnect between analysts and what J&J has been seeing to close now as people see the full potential. SubQ is going to be key to achieving that because, as you know, our data showed a reduction in the infusion-related reactions from about 76% with the IV down to the teens with the subQ, as well as much shorter infusion times. So it's just going to be, I think, a nice combination of the subQ once it's resubmitted and approved.
And I'll mention we don't have any milestones for a potential amivantamab approval in our projections for 2025 at this time until we get some line of sight as to resubmission, et cetera. But we are very confident that J&J will be resubmitting that, and there's going to be an incredible excitement. So that combination of the better profile with the subQ and this excellent data bodes very well for a strong uptake for amivantamab subQ upon approval.
Got it. Thanks very much. That's very helpful.
Your next question comes from Michael DiFiore from Evercore ISI. Your line is now open.
Hi, guys. Thanks so much for taking my questions and congrats on the updated outlook. A few from me. Just any updates on the status and prospect of new deals? I noticed that the collaboration revenue guidance for 2025 has decreased slightly. Anything to read into that? And additionally, has there been any partner interest in ENHANZE at this point? And finally, have you considered, or is it possible that you will eventually disclose XYOSTED sales? Thank you.
Thanks for those, Mike. So yes, on the collaboration milestones for 2025, the real reason for the change of that, which, as you note, was previously 130 - 160 down to 100- 130, is the change in expectations for approval timeline for amivantamab. There are several milestones associated with launches in different countries. And because we don't have visibility into that timing, we elected to take out that, which obviously would be upside if there is an approval in 2025. So that really doesn't reflect anything to do with new deals. It is simply related to the uncertainty on timing for amivantamab.
On the status of new deals, yeah, we are continuing to expect to sign additional enhanced high-volume and small-volume autoinjector deals in 2025. As we reflected on 2024, I think what we have concluded at the end of the year is a fact well known to investors that the current pharma and biopharma companies are certainly more financially constrained than historically, and this is leading to longer timelines and longer processes to go decisions. I can say that the conversations we are having, the breadth of the conversations remains at an all-time high, both with companies coming to us about enhancing the gold standard for subQ delivery, but also in response to our outreach, and we've continued in multiple conversations on each of our opportunities, the enhanced, the high-volume, and the small-volume, but what we're seeing is very slow-go to decision-making.
I'll highlight that by saying, if you remember, in 2024, I talked about several companies being at terms discussion. That usually is the stage that once we align on terms, we move forward to negotiate the actual CLA. What we're finding is while we have satisfactorily reached general agreement on the terms, companies are still pausing at this point in time to finalize the go to the contract, often based on internal discussions continuing, sometimes based on financial conversations, that type of thing. Now, what does this mean in 2025 and beyond for new deals? I will say based on the conversations we're having and the meaningful value that ENHANZE and our high-volume autoinjector are delivering, I remain very confident in new deals.
It certainly has been slower than we want, certainly slower than we expect, but the conversations give me absolute confidence there will be additional deals to come, and in parallel, I'll just remind you that we also continue to talk to our current partners about the potential for them moving new nominations based on their open slots into the clinic, so this combination gives us confidence that we have included meaningful revenue in 2025 projections related to new deals based on this confidence. With regard to partner interest in ENHANZE, recall the ENHANZE will be for companies who are using a modified hyaluronidase who can't or don't want to use ENHANZE and who are wanting, however, to access our pioneering IP that would be required to be using these for delivery of subQ.
And so the majority, vast, vast majority of our conversations continue to be with ENHANZE and not on Hylenex. But we continue to signal and communicate how open we are for companies to approach us if they are using a modified hyaluronidase and want to utilize our IP. With the XYOSTED numbers, we are reporting our product sales in a group, and it's not our intention and plan at this point in time to separate that out. I will say we're continuing to see some very nice growth in XYOSTED, which really does offer a terrific offering for people who need testosterone replacement with a simple multi-second weekly subcutaneous injection. But no plans at this time to break it out, but I will say very pleased with the growth there.
Thanks so much.
Your next question comes from Jason Butler from Citizens JMP. Your line is now open.
Hi, thanks for taking the questions, and I appreciate all the details given this morning. Can you maybe talk about use of capital and how you think about obviously announcing the accelerated buyback today, but prioritizing buyback or other tools versus potential for additional acquisitions or business development activities? Thanks.
Yep. Let me turn that over to Nicole.
Yeah, thanks, Jason. And happy to share today the strong business progress really results in strong cash flows. So we look at our cash flows. We maintain our balanced approach to allocating our capital. So after investing in our business, we evaluate opportunities for share repurchases and for M&A. And what we saw at the end of the year is we don't have identified an M&A opportunity. And that's why we did move forward with initiating allocating and committing $250 million to share repurchases. So you've seen us do that in the past, and you'll see us continue to evaluate our opportunities in the same way and deploy our capital in that way to drive value for shareholders.
Your next question comes from Jessica Fye from JPMorgan Chase. Your line is now open.
Hey, guys. Good morning. Thanks for taking my question. You've got an impressive outlook over the next several years. Many of the investor questions we hear are about how to think about the long term. Is there any color you want to put around how investors should think about growth beyond this timeframe? So thinking 2029 plus?
Yeah, thanks, Jess. As we, obviously, I think we're a very rare company to be putting out multi-year guidance out so many years as we do. But we do know there is interest in 2029.
Now, what's important to note in the guidance we put out to date, particularly the royalty revenues, which are the core drivers, we are only including the nine approved products and amivantamab in those current projections. And that's because we wanted to give investors a lot of confidence on the de-risk nature of these royalty revenues. So as we think about what's going to happen in 2029 and beyond, we've got the opportunity to have additional royalty revenue streams on top of that. I'll highlight the additional indications for VYVGART Hytrulo, which will potentially be beginning in the 2026, 2027 timeframe. Those will be another layer on top of this because currently we only include gMG and CIDP. We also have multiple products that we refer to as our wave four products. These are products that are currently in phase one or phase three development.
These have the potential, obviously, to be contributing at that time as well, not included currently. And then, of course, we continue to work to sign new collaboration agreements and deals and to move new partner products forward from our current partners. Those represent additional royalty revenue streams as well. So a lot of potential based on what we already have line of sight to, but also new deals, new nominations to be adding and contributing to growth after 2029.
Thank you.
Your next question comes from Mitchell Kapoor from H.C. Wainwright. Your line is now open.
Hey, everyone. Thanks for taking the questions. I wanted to ask about how you're thinking about benchmarking the initial quarters of launch for OCREVUS, TECENRIQ, and OPDIVO subcutaneous formulations. Obviously, you won't see meaningful growth until next year, I think you mentioned. But what metrics are you looking for, and what are the internal benchmarks that you're thinking will help decide whether these are overwhelming successes or on par with your expectations? And then separately on the BD front, if you could just talk about how you're thinking about BD given the Evotec trajectory. And if you could just talk about, are you looking at deals that are kind of similar, or could you define the scope of what could be interesting to Halozyme at this time?
Yep. I'll talk about the benchmarks, and then I'll turn it to Nicole to talk about what our approach to M&A is. So quite right, Mitch, in terms of looking at the trajectory, we do know that it takes a period of time, and the U.S. is different from Europe, and we gave our estimates. It's slow at the start. It always is.
That's certainly what we model, at least six to nine months in the U.S. before you start to see that uptake as physicians become comfortable in reimbursement, but also outside the U.S., 12 months plus. That's why we've signaled that for 2025, we certainly have very modest expectations for the contribution of these products. I think the companies talking, and I'll say as an example, argenx is doing that on CIDP to talk about the amount of coverage they're gaining. Those are going to be key, I think, metrics to show that things are on track for these products contributing meaningfully in 2025. Then, obviously, they'll contribute meaningfully in 2026. If I think what to listen for in our partner calls, it would be that talking about the coverage.
I think in the case of OCREVUS, we're hopeful they'll talk about new prescribers and how many new prescribers and new-to-brand patients that they're seeing. Again, that has been very helpful, I think, in the color that argenx has been providing on VYVGART Hytrulo. So I focus on those types of things. And as you point out, 2026 really will be the year where each of these products is in a strong position for uptake. Let me turn it to Nicole to talk about our criteria for M&A.
Yeah, thanks, Mitchell. When we're looking at M&A, our criteria really has remained unchanged. And it's what we saw in Evotec, and it's what we'll continue to look for as we screen potential targets that are really focused around assets that will extend our revenue in our EBITDA. We're very focused on de-risk businesses.
We're looking for businesses that have similar structures, meaning long, durable, predictable revenue streams similar to ENHANZE. And we're also looking for businesses that have strong partnerships with marquee biopharma companies similar to our current business model today. So again, really focused on those business models that we see that can add diversification, extend Halozyme's revenue, enhancing our long-term growth, and really adding to our existing robust long-term margin profile and our significant cash generation over time.
Okay, great. Thank you. Very helpful.
Your next question comes from David Risinger from Leerink Partners. Your line is now open.
Yes, thanks very much. And let me add my congrats on the strong financial momentum. So I just have a couple of questions, please. First, I know that you excluded amivantamab milestones for 2025, but could you please remind us what the dollar amounts of those milestones will be in the future? And then second, the OPDIVO subcutaneous conversion in the U.K. has been quite rapid. Could you provide an update on that, please? Thanks very much.
All right. And David, can I just clarify? OPDIVO subQ, do you mean TECENRIQ subQ in the U.K.?
Sorry, yes, TECENRIQ subQ. Correct.
All right. I was going to say that's very fast. All right. So with regard to the milestones, again, it's not our practice to provide forward-looking to the milestones, but I will say the amivantamab milestones, you can consider that those were tracked very similarly to DARZALEX because it's the same contract for biologics there. And so if you were to look back historically, you would see that we do get meaningful milestones overall for the first product sale done in each of the regions. So regions are usually U.S., Europe, and Japan.
And so that, I think, can give you an idea. And I did comment that we had modified our guidance to reflect a change of $30 million with regard to the outlook for collaboration milestones this year. And that really is driven by that amivantamab change. So hopefully, that gives you sufficient color to track back to that. With regard to TECENTRIQ subQ in the U.K., I will say that the U.K. is a market that has always adopted subcutaneous products. That really is because they are very focused on the overall cost of care, but also the convenience of care for patients. And so we don't have any more recent updates from what Roche has talked about, where it did very rapidly in a couple of quarters get to close to 40% conversion, if I recall that correctly.
I do expect that to have continued, and we look forward to Roche providing updates on the uptake of TECENTRIQ. But exactly as we would have expected, and we expect to see it in multiple European markets. If we look back to Herceptin, to MabThera, the U.K., Nordic countries, multiple companies get out of the gate incredibly fast because the healthcare systems recognize the overall increased value of a subQ versus IV and can institute a very rapid conversion.
Great. Thanks very much for that additional color.
Thanks, David.
If you'd like to ask a question during this time, please press star followed by number one on your telephone keypad. That's star followed by one on your telephone keypad. Your next question comes from Mohit Bansal from Wells Fargo. Your line is now open.
Great. Thank you very much for taking my question, and thanks for the update here. Just wanted to talk a little bit about the VYVGART and next generation FcRn. So if I understand correctly, you are partnered with argenx on the next generation FcRn as well. In the product and pipeline approach, do you get a sense that argenx is working with the next generation FcRn for the newer indications versus the VYVGART? And the clarification question is that if argenx were to go with the next generation FcRn, would the royalty terms be similar to VYVGART, or would they be different versus what VYVGART terms are right now? Thank you.
Yes, thanks, Mohit. If you were to kind of go to ClinicalTrials.gov, you would see an expansive set of new studies that have been initiated with VYVGART Hytrulo.
To answer your question, they are doing the new indication expansion in areas like ocular myasthenia gravis, myositis, Sjögren's, antibody-mediated rejection, systemic sclerosis, thyroid eye disease, and bullous pemphigoid, all with the original VYVGART Hytrulo. That is where the focus is to build that product into this massive blockbuster through this pipeline in a product approach. Very much focused on those products today, and that's where the clinical studies are. With regard to the terms, yes, the terms would be similar for a second FcRn as they are to the current VYVGART Hytrulo. Thank you. Which I'll just remind you are mid-single-digit royalties for the first 10 years after the first commercial launch, which obviously is very attractive given what strong products argenx is developing and launching.
Got it. Thank you.
Your next question comes from Joe Catanzaro from Piper Sandler. Your line is now open.
Great. Hey, everybody. Thanks for the update, and thanks for taking my question. I had one, maybe a follow-up to our earlier question on OPDIVO subQ approval. Wondering if you had any thoughts specifically around the breadth of the label coverage as it relates to indications and combinations there, and whether you think that label aligns with Bristol's previous comments of converting 30%-40% of the IV market, or is that 30%-40% potentially conservative relative to the label specifics that we now know there? Thanks.
Yes, thanks, Joe. Yeah, obviously, we were delighted to see the approval at the end of the year. And certainly, from a Halozyme perspective, it was pretty much in line with what we had expected based on the comments from Bristol.
In terms of Bristol's assessment of the label and whether they're going to change their estimates, which obviously are very attractive to get an overall conversion of 30%-40% of this $10 billion brand over time, I think we'll have to wait and see if they're going to make comments on that at their upcoming meetings and presentations. But certainly, for Halozyme, in line, and very pleased to see that once again, on a single study in renal cell carcinoma, they achieved approvals in a broad range of different solid tumors, giving a much more streamlined and more cost-effective approach to get new approvals for a subQ version based on a successful IV drug.
Okay. Got it. That's helpful. Thanks for taking my question there. Thank you.
Thanks, Joe.
This concludes the question-and-answer session. Thank you for attending today's conference call. You may now disconnect.
Have a wonderful day.