Halozyme Therapeutics - Q4 2023

Transcript

Operator (participant)

Hello and welcome to the Halozyme fourth quarter and fiscal year 2023 financial and operating results conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session, and if you would like to ask a question during this time, simply press star one on your telephone keypad. I will now turn the conference over to Tram Bui. Please go ahead.

Tram Bui (VP of Investor Relations and Corporate Communications)

Thank you, operator. Good afternoon and welcome to our fourth quarter and full year 2023 financial and operating results conference call. In addition to the press release issued today after the market close, 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 would be Dr. Helen Torley, Halozyme's President and Chief Executive Officer, who will provide an update on our business, and Nicole LaBrosse, our Chief Financial Officer, who will review our financial results as well as our outlook. On today's call, we will be making forward-looking statements as outlined on slide 2. I would also refer you to our SEC filings for a full list of risk 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 earnings press release and slide presentation. I'll now hand the call over to Dr. Helen Torley.

Helen Torley (President and CEO)

Thank you, Tram, and good afternoon, everyone. Moving to slide 3. We're very pleased to report our strong financial and operating results in the fourth quarter and for the full year of 2023. These results are driven by our two leading differentiated drug delivery technologies ENHANZE and our auto injectors, and also by our two commercial products, XYOSTED and Hylenex. Moving to slide 4. For 2023, we delivered a 26% year-over-year increase in total revenue to $829 million and reached a record $448 million in royalty revenue, which represents a 24% year-over-year increase. Strong operational performance drove another year of double-digit earnings growth, with Adjusted EBITDA increasing 19% to $426 million and non-GAAP diluted earnings per share growth of 25% to $2.77 for the full year 2023. We also deployed $400 million to shareholders through share repurchases, reflecting strong cash flow and disciplined capital allocation priorities.

Moving to slide 5. Our achievements and our partner progress in 2023 contributed to the strong performance and paved the path for our strong long-term outlook. The total number of ENHANZE commercial products increased in 2023 from five to seven, with the approval of argenx's VYVGART HYTRULO for generalized myasthenia gravis in the U.S. and Europe, and the approval of Tecentriq subcutaneous in Great Britain. We also had multiple positive phase III data readouts, supporting regulatory submissions for approval of the ENHANZE subcutaneous formulations. Recall that we have a 100% success rate for approval of products delivered subcutaneously with ENHANZE when the phase III trials have met their endpoints. VYVGART HYTRULO phase III data in CIDP was the first positive phase III readout, and upon approval, creates an expanded commercial opportunity in a condition where there is high unmet need today.

argenx has already submitted the supplemental BLA for this indication using a priority review voucher, which would support a potential approval by mid-year of 2024. We were also very excited with the positive data announcements from two additional phase III products, Roche's ocrelizumab subcutaneous with ENHANZE and Bristol-Myers Squibb's nivolumab subcutaneous with ENHANZE, supporting global regulatory submissions and potential launch in 2024 for ocrelizumab sub-Q and in 2025 for nivolumab sub-Q. We also continued to advance and expand our pipeline. Johnson & Johnson presented data at ASCO from the phase I amivantamab sub-Q with ENHANZE trial. An important observation that was highlighted was the dramatically lower rate of infusion-related reactions, with the subcutaneous at 16% compared to 67% reported with intravenous amivantamab, which is commercialized as RYBREVANT.

Infusion-related reactions can include mild symptoms such as chills, breathlessness, and nausea, but can also be severe, making this reduction, if confirmed in the phase III study, very meaningful to physicians. We are delighted that Johnson recently announced strong progress with the phase III study, that they project will support submission of regulatory filings in 2024 for subcutaneous amivantamab with ENHANZE. Another significant achievement was ViiV advancing testing of their broadly neutralizing antibody N6LS for HIV. Also in 2023, we reached an important milestone for our new high-volume auto injector, as we successfully demonstrated the feasibility of administering a subcutaneous injection of 10 ml of a representative biologic immunoglobulin 10% with ENHANZE in approximately 30 seconds using our high-volume auto injector. We were pleased to add a new ENHANZE partner, Acumen Pharmaceuticals, in the fourth quarter.

We're delighted to be working with them to develop a subcutaneous delivery option for ACU193, bringing together Acumen's deep understanding of Alzheimer's and the amyloid beta oligomers with our enhanced platform. Moving now to slide 6. With our strong track record of success and progress, as we look ahead, we have high confidence in the visibility of our revenue, and we were delighted to recently share our 2024 guidance on our five-year financial outlook for the company. For 2024, we're delighted to project continued strong growth of revenue with a guidance range of $915 million-$985 million, representing 10%-19% year-over-year growth. Royalty revenue remains our top driver of our revenues and is projected to be $500 million-$525 million, representing growth of 12%-17%.

As a result of our disciplined approach to expense management and our business model, we are projecting Adjusted EBITDA in the range of $535 million-$585 million, a remarkable 26%-37% growth. I'll focus now on the five-year financial outlook. Total revenue is projected to reach $1 billion in 2025 and grow to greater than $1.5 billion+ in 2027 and 2028, with royalty revenue continued to be the key driver projected at $1 billion in 2027. Impressively, we project Adjusted EBITDA will grow faster than revenue in every year of the five-year outlook to an impressive $1 billion in 2028, with a five-year CAGR of 23%. I'll now turn to slide 7 and review royalty revenue drivers in a bit more detail.

Our wave two products, DARZALEX FASPRO and Phesgo, launched in 2020, have driven the impressive royalty revenues and growth illustrated on this chart and have many years of impressive growth ahead for them. Moving now to slide 8 and to DARZALEX FASPRO enabled by ENHANZE. With subcutaneous penetration in excess of 90% in the U.S., total brand growth has become the key driver for understanding subcutaneous performance for this product. In 2023, total DARZALEX sales continued to deliver strong growth for Johnson & Johnson, increasing approximately 23% year-over-year on an operational basis to $9.7 billion. This strong growth was driven by share gains in all regions and continued growth in the first line setting.

Supporting future growth in first line, it is notable to highlight that Johnson & Johnson recently submitted a supplemental BLA to the FDA to support a new indication for DARZALEX FASPRO with ENHANZE for multiple myeloma in newly diagnosed adult patients who are eligible for autologous stem cell transplant. The results from their PERSEUS study, recently published in the New England Journal of Medicine, supported this submission. The addition of DARZALEX FASPRO to standard of care treatment resulted in a statistically significant and clinically meaningful improvement over today's standard of care alone in progression-free survival, complete response or better, and minimal residual disease negativity. As we look forward, analysts continue to expect annual sales of DARZALEX to grow to approximately $17 billion by 2028, driven in large part by the first line opportunity. I'll move now to Phesgo, which is illustrated on slide 9.

Phesgo offers the potential for patients with breast cancer to receive treatment as a simple subcutaneous injection over 5 minutes after the first dose and a total treatment and observation time of about 20-38 minutes, which compares to 2.5 to 7.5 hours total treatment and observation time for the IV. With this strong value proposition, Phesgo's sales continued at an impressive rate of growth in 2023, increasing 64% to CHF 1.1 billion for the full year as Roche continued to expand into additional markets while also driving global conversion rates higher. Roche reported a 39% conversion rate in 46 launch countries. As we look at regional uptake, strong growth and contribution was reported for all regions. U.S. sales were CHF 423 million, growing at 48% and now representing close to 40% of total revenue.

EU is growing at 52%, and international was reported to be growing at greater than 150%. Roche stated that it expects continued growth of Phesgo with increasing conversion from the IV treatment PERJETA, which reported sales of CHF 3.8 billion in 2023. With Roche projecting peak conversion of approximately 50%, we are excited to see the strong performance and the future growth that lies ahead for Phesgo. I'll now move to slide 10 and a focus on our wave three products and product candidates. What you see in the left panel are the 2023 launches, and as you move across the slide to the right, the multiple product, regional, and indication launches that are projected this year and next.

I will highlight that positive phase III data and regulatory submission plans have been reported by our partners for all products, with the exception of amivantamab that has not yet reported its phase III data. We are very excited with the large opportunity for the wave three, which is now comprised of five products that are projected by analysts to generate total sales of approximately $35 billion in 2028. I will start with VYVGART HYTRULO with ENHANZE, which was approved in generalized myasthenia gravis in the U.S. in June of 2023 and in Europe in November. VYVGART HYTRULO with ENHANZE offers myasthenia gravis patients a new faster treatment delivery option delivered by healthcare practitioners in just 30 to 90 seconds. Notably, the European approval also allows for patient self-administration subcutaneously.

With the VYVGART HYTRULO subcutaneous launch just six months ago, argenx's focus has been on broadening commercial coverage and securing the J-code, which was accomplished in January of this year. With this, we project growing adoption for VYVGART HYTRULO. The successful launch of VYVGART with $1.2 billion in revenue in 2023 supports the unmet needs that exist for the treatment of generalized myasthenia gravis and the attractiveness of the VYVGART clinical profile. VYVGART HYTRULO adds the potential to expand the number of physicians using VYVGART and to expand use in the earlier lines of treatment. I'll now move to an exciting additional opportunity for VYVGART HYTRULO, and that's CIDP or chronic inflammatory demyelinating polyneuropathy. Based on argenx's research and recent comments, 42,000 patients receive treatment today for CIDP. It's a condition where there is a high unmet need.

Just 20% of patients get remission on the current standard of care treatment, and 50% of patients report that they remain dissatisfied with the current burden of symptoms. The 61% reduction in risk of relapse with VYVGART HYTRULO versus placebo shown in the ADHERE study would, upon approval, offer an important new option for patients. I'll highlight that this indication will be available only as a subcutaneous treatment enabled by ENHANZE. With the recent submission and use of their priority review voucher, argenx projects the possibility of approval for this new indication in the United States in mid-2024. Moving now to Tecentriq. Tecentriq, as an IV, remains a key growth driver for Roche, with revenue growing 9% year-over-year to CHF 3.8 billion in 2023.

Tecentriq subcutaneous with ENHANZE was granted regulatory approval in Great Britain last year and in the European Union in January of 2024 for all of the approved IV indications. It is given as an approximately seven-minute subcutaneous delivery, which compares to 30 to 60 minutes for the IV infusion. With U.K. conversion already reaching 18%, essentially in one quarter, Roche believes that the opportunity for subcutaneous adoption remains significant. The U.S. approval is projected in September of this year. Moving now to OCREVUS. OCREVUS, as an IV, is the leading treatment in the U.S. and EU5 for multiple sclerosis, with more than 300,000 patients treated globally and a higher retention rate than other multiple sclerosis medicines. For the full year, OCREVUS generated an impressive CHF 6.4 billion, which we estimate to be about $7 billion, in revenue for Roche, which represents 13% year-over-year growth.

OCREVUS subcutaneous with ENHANZE creates a possibility for people living with multiple sclerosis to receive their treatment in just 10 minutes twice a year, which compares to 3.5 to 6.5 hours for the IV treatment and observation time. Roche commented on their recent quarterly call that they project the addition of availability of OCREVUS subQ, which is enabled with ENHANZE, to create a standalone blockbuster opportunity. As we have seen with DARZALEX subcutaneous, the availability of the subcutaneous delivery option can result in or accelerate market growth. We project the availability of ocrelizumab subcutaneous with ENHANZE can create increased growth in two key ways. Firstly, by allowing current multiple sclerosis centers to increase the number of patients treated as a result of improved throughput based on shorter time needed for each patient occupying an infusion chair.

Secondly, by expanding the number of treatment centers, by enabling multiple sclerosis centers that do not have IV infrastructure today to start administering ocrelizumab subcutaneously. Following the completed regulatory submissions in the U.S., EU, and U.K. in 2023, we project the approval of ocrelizumab subcutaneous to represent our eighth ENHANZE royalty revenue generating product in 2024. Our next wave three product is Bristol-Myers Squibb nivolumab subcutaneous with ENHANZE, which is the brand name Opdivo as the IV. Opdivo IV sales were $9 billion in 2023, increasing 9% year-over-year, showing continued strong growth. In January, Bristol-Myers Squibb presented the detailed results of Checkmate 67T, the phase III IV versus subcutaneous registration enabling study at ASCO GI. As announced previously, the trial met the primary endpoint of non-inferiority of the two co-primary endpoints, C average over 28 days and C min.

A key powered secondary endpoint of overall response rate was also reported. Non-inferiority was also demonstrated with the overall response rate of 24.2% for the subcutaneous and 18% for the IV. Given in just five minutes, nivolumab subcutaneous has the potential to be practice changing and to improve the patient's treatment experience. Bristol-Myers Squibb commented that the subcutaneous could potentially extend the franchise through the end of this decade and into the early 2030s, with the subcutaneous approval projected to cover up to 75% of the IV indications. Lastly, we were excited to have recently added Johnson & Johnson's amivantamab subcutaneous with ENHANZE into our wave three potential launches, with the potential for launch in 2025. Johnson & Johnson recently indicated that they expect phase III data from the MARIPOSA trial for amivantamab with ENHANZE plus lazertinib in 2024, supporting U.S. and European regulatory filings also in 2024.

amivantamab is already approved as an IV under the brand name RYBREVANT, with Johnson & Johnson projecting RYBREVANT will become a multibillion-dollar brand. Let me now move to slide 11, where I'll provide an update on our wave four pipeline, which is projected to support our future growth trajectory with potential launches in the 2025 to 2027 timeframe. We currently have a robust pipeline with seven exciting products in development. This reflects amivantamab moving to wave three based on the updated potential launch timing and Amgen's decision to not move forward with a subcutaneous version of TEPEZZA with ENHANZE. Johnson & Johnson have also made the decision to not proceed with approving subcutaneous. The wave four portfolio comprises products across a range of therapeutic areas, including oncology, neurology, immune disease, and HIV. We have two products in phase III development.

This includes Bristol-Myers Squibb nivolumab with relatlimab with ENHANZE, where the phase III study is underway. The IV version of Opdualag is projected by analysts to be a multibillion-dollar brand in 2028. The goal with the subcutaneous version is to offer a shorter, simpler treatment option, reducing patient burden and healthcare resources. Takeda's TAK-881, which is a 20% IgG with ENHANZE for primary immune deficiency, is the second phase III development program. This would be the second 20% IgG to launch and will expand Takeda's immune globulin offering for patients, creating a lower volume and potentially shorter treatment schedule. Last year, our ViiV collaboration also progressed with subcutaneous delivery of N6LS enabled by ENHANZE. N6LS is a broadly neutralizing antibody for HIV, and it is advanced into a phase IIb study in combination with cabotegravir as a two-drug regimen for HIV treatment.

Because of the rapidly changing nature of HIV and its potential to develop resistance to certain treatments, ViiV, based on HIV community feedback, has stated that there continues to be a need for medicines with unique mechanisms of action like the broadly neutralizing antibodies, which may open up a completely new approach to treating HIV. Separately, we continue to be pleased to collaborate with argenx on ARGX-117, now named empasiprubart. In addition, we have two remaining programs in wave four that are confidential at the request of our partners. I'll move now to slide 12. Let me now spend a moment on our high-volume autoinjector. We were excited last year to demonstrate delivery of 10 mL of a representative biologic co-formulated with ENHANZE in just 30 seconds with our innovative new high-volume autoinjector. ENHANZE is the key ingredient that makes this possible.

For patients, this can offer the option for home delivery or rapid delivery in the physician's office. Our goal with the high-volume autoinjector offering is to expand upon established enhanced collaborations and add new collaboration partners. I'm pleased to announce that one of our current partners is initiating a Human Factors Test of the high-volume autoinjector to evaluate device usability. This test is scheduled to start this quarter. I'll turn now to new enhanced deals. We continue to have strong and expanding interest by existing and new partners. While we were disappointed by the slow progress in decision making by companies in 2023, we remain confident in our ability to expand our pipeline in 2024.

This year started with expanded interest from potential new partners with a busy schedule of meetings in January and February already, with partners expressing interest in ENHANZE, the high-volume autoinjector, and in some cases, the small-volume autoinjector technology. I look forward to providing updates and progress on new agreements throughout the year. I'll now turn to our commercial portfolio. XYOSTED sales achieved $100 million in 2023, demonstrating strong growth. This sales attainment met our target revenue for the year and break even in the fourth quarter. This performance reflects successful execution of our three-pronged strategy, which includes targeting the switch of patients who are not achieving their treatment goals with intramuscular injections, enhancing adherence with specialty pharmacies executing educational programs to support patients staying on treatment, and continued actions to improve the net sales price.

With a market of more than 9.5 million scripts a year and our share approaching 5%, we see a clear path for continued growth in revenue and EBITDA contribution in 2024, with a CAGR projection of 25% through 2028. Let me now turn the call over to Nicole, who will discuss our financial results in more detail.

Nicole LaBrosse (Senior VP and CFO)

Thank you, Helen. The fourth quarter marked a strong end to 2023. We delivered double-digit revenue growth and achieved another record quarter of royalty revenue. Adjusted EBITDA and diluted earnings per share growth outpaced the top line, reflecting the significant leverage we generate as we grow royalty revenue. Let me start with capital allocation on slide 13. We remain committed to our three capital allocation priorities of investing in the business to maximize revenue growth and durability, returning capital to shareholders through share repurchases, and adding new growth opportunities through M&A.

In November 2023, we initiated a $250 million Accelerated Share Repurchase, or ASR. This will operate to repurchase our shares for a number of months into 2024. This brings our total share buyback since the inception of the first program in 2019 to $1.3 billion. I am also pleased to announce that our board authorized a new $750 million repurchase program, reflecting our continued commitment to balanced capital allocation and a focus on driving value for shareholders. Turning now to slide 14 for our detailed financial results for the fourth quarter of 2023. Revenue for the fourth quarter grew 27% to $230 million, compared to $181.5 million in the prior year period. Royalty revenue for the quarter was $122.1 million, an increase of 15% compared to $106 million in the prior year period, driven by continued strong performance of wave two products, subcutaneous DARZALEX and Phesgo.

Note that Q4 of 2022 reflected a measurement period adjustment to amortization of intangibles to our current run rate of $17.8 million a quarter. Other operating expenses remained relatively flat period over period due to our leverageable business model, resulting in Adjusted EBITDA growth of 47% to $121.7 million from $83 million in the prior year period. Our cash, cash equivalents, and marketable securities were $336 million as of December 31st, 2023, compared to $483.3 million as of September 30th, 2023. The reduction is due to the use of $250 million for the ASR, offset by positive cash generation in the quarter. We ended the quarter with a net leverage ratio of 2.5x, and we expect to decrease net leverage each quarter with EBITDA growth. Turning now to slide 15 for our detailed financial results for the full year 2023.

I will briefly touch on some highlights here with more details available in our press release and the 10-K filed with SEC today. Recall that we closed the Antares acquisition on May 24th, 2022, and therefore, the year-over-year comparison is impacted by a full year versus a partial year of contribution from the Antares business. Total revenue grew 26% year-over-year to $829.3 million in 2023, off an already substantial revenue base in 2022 of $660.1 million. The main contributor to this increase was higher revenue from royalties of $447.9 million, reflecting growth of 24%, as well as higher enhanced product sales and XYOSTED sales growth. Also note that the revenue growth was offset by the timing of milestones recognized in the prior year.

Recall that the timing of a milestone for Tecentriq SC in the U.S. was planned for the third quarter of 2023 and is now expected in September 2024. Research and development expenses were $76.4 million compared to $66.6 million in 2022, primarily due to increased compensation expenses resulting from the addition of a new platform, our device platform, as well as planned investments in ENHANZE. Selling, general, and administrative expenses were $149.2 million compared to $143.5 million in 2022, primarily due to the addition of resources and sales and marketing with the addition of our commercial product, XYOSTED, offset by one-time transaction costs related to the Antares acquisition that occurred in the second quarter of 2022 of approximately $38 million. Adjusted EBITDA increased 19% to $426.2 million from $358.9 million in the prior year period. GAAP diluted earnings per share was $2.10, and non-GAAP diluted earnings per share was $2.77.

This is compared with GAAP diluted earnings per share of $1.44 and non-GAAP diluted earnings per share of $2.21 in 2022. Turning now to slide 16 in our 2024 guidance. We are reiterating our top line Adjusted EBITDA and non-GAAP diluted EPS guidance for the full year 2024 that was provided in January. We are projecting another year of double-digit revenue growth to $915 million-$985 million, with milestones and API sales to be substantially weighted in the second half of the year. Royalties are growing to $500 million-$525 million, with a flattening in the first and second quarter and growth sequentially thereafter. With royalty revenues for the year greater than 50% of total revenue, this directly impacts gross margin expansion, resulting in Adjusted EBITDA growth of 26%-37% to $535 millon-$585 million.

When coupled with our 2023 share repurchases, non-GAAP diluted EPS growth is outpacing the top line growth at 28%-41% to $3.55-$3.90. With that, I'll now turn the call back over to Helen.

Helen Torley (President and CEO)

Thank you, Nicole, and thank you to all of the Halozyme team, our partners, and collaborators on a strong 2023. I'm very excited for the opportunities that lie ahead for Halozyme. Our disruptive drug delivery technologies continue to demonstrate strong value to our partners and to patients. As the market leader, we are well positioned to capitalize on the significant market opportunities ahead for subcutaneous delivery technologies and to deliver strong, durable revenue and EBITDA growth. With that, operator, we're pleased to open the call for questions.

Operator (participant)

Thank you. If you have a question, please press star one on your telephone keypad. To withdraw your question, simply press star one again. Your first question comes from the line of Jessica Fye with JPMorgan. Your line is open.

Jessica Fye (Managing Director and Equity Research Analyst of Biotechnology)

Hey, guys. Good afternoon. Thanks for taking my question. Just a couple here. I guess first, what are your goals for signing new partnerships this year? And second, how quickly can you deploy the $750 million share repurchase authorization? Thank you.

Helen Torley (President and CEO)

Thanks, Jess. I'll take the first one. We certainly are off to a great start in 2024 with a robust set of meetings and forward momentum across all of our opportunities. That includes ENHANZE, the high-volume autoinjector, and the small-volume autoinjector. Our focus is on progressing all three of these types of deals. We're not putting a specific number on it, but we're looking to advance all of these and look forward to updating you on that progress throughout the year. Nicole, will you tackle the question on this share repurchase new program?

Nicole LaBrosse (Senior VP and CFO)

Yeah, thanks, Jess. So at the moment, we are actively repurchasing shares today. Recall, towards the end of 2023, we initiated a $250 million accelerated share repurchase program that operates for a number of months into 2024 to buy those shares. So that is active at the moment. And we were happy to announce the approval of the new program, and the purpose of that is to continue to execute on our capital allocation strategy and continue to utilize that to continue to look at share repurchases into 2024 and beyond.

Jessica Fye (Managing Director and Equity Research Analyst of Biotechnology)

Thank you.

Operator (participant)

Question comes from the line of Michael DiFiore with Evercore ISI. Your line is open.

Michael DiFiore (Director of Biopharma Equity Research and Publishing Analyst)

Hey, guys. Thanks so much for taking my questions, and congrats on all the progress in 2023. Just two questions from me. With regards to the amyloid beta target for ENHANZE, obviously, this is a non-exclusive deal. Have there been any more partner companies that have opted into co-license this target, and any commentary on when we might find out who the other co-licensee is? Separately, I was wondering if there had been any development or updates to the timelines for the room temperature and high yield, hyaluronidase, and whether any potential partners have expressed interest in this. Thank you.

Helen Torley (President and CEO)

Thanks, Mike. With regard to amyloid beta, obviously, we were delighted last year to sign the deal with Acumen. We don't have any other partner agreements we can announce with regard to that, but it continues to be an area of focus for us because we do believe there is a strong value proposition for Alzheimer's patients in being able to receive their therapy as infrequent as possible, simple subcu dose, even at home. So we remain in active dialogue with regard to that. The company that already had the non-exclusive license, that really is up to that partner. And I think, Mike, will depend on whether they are advancing in clinical development. That is not an active program at this point in time. So it really would be up to them if they did decide to disclose it at that period of time.

But definitely an exciting area, and we're delighted to be working with Acumen. For the room temperature stable, just to remind everybody, this is a different version than ENHANZE. It's another hyaluronidase, which has its own patent life out to 2032 in Europe and 2034 in the United States. Now, we brought forward as a possibility to use with partners who perhaps wanted a product like a small molecule that patients would carry around with them. Obviously, the majority of our products are refrigerated today, and so ENHANZE is just perfect for that. We have advanced the development of that to have established a new cell line for it. We are ready to go to scale up, and we're still in conversations, although they're early conversations with at least one partner about potentially moving that forward.

But so far, no decision to move forward with that, but we're ready to go to the next stage. Now, this is a full development. And just to give an expectation of the timeline, we'd expect this to be available post-2027 as there is work to be done to finish the scale up, but also any program going through with the new room temperature would have to go through our standard phase I, phase III program, which on average takes about five years. So hopefully, that's helpful in describing the timeline for it. There are a few companies interesting. I will say most people, ENHANZE is exactly what they need. That's where we expect the majority of partners to go. But this was an additional offer, and we thought might work for a nice small target number of opportunities, and we continue to talk about that.

Michael DiFiore (Director of Biopharma Equity Research and Publishing Analyst)

Great. Thanks so much.

Operator (participant)

Your next question comes from the line of Mohit Bansal with Wells Fargo. Your line is open.

Mohit Bansal (Equity Research Analyst)

Great. Thank you very much for taking my question. Two questions, if I may. One, so in your 10-K, there is some comment around cancellation of the TEPEZZA partnership with Horizon. If you could elaborate a little bit more. I know there was not a lot of progress made before the company got acquired by Amgen, but any comment, any color you could provide there. And the second question is regarding the infusion time reduction, right? So for Tecentriq and OPDIVO, you're talking about 30 minutes coming down to 5 minutes or so. How big is a factor this infusion time reaction in terms of conversion? Does it play into I mean, some conversions are more like 50% or less versus DARZALEX is a really high conversion story. So could you talk a little bit about that? Thank you.

Helen Torley (President and CEO)

Yeah, pleased to do that. With regard to the Amgen agreement now with TEPEZZA, all we can say, Mohit, is that very recently, Horizon informed us that they were ending the agreement and licensing agreement with ENHANZE. They didn't provide any further information, and so there's no additional information we can share on that. And as you note, that had not been progressing with Horizon for a period of time as we kept everybody informed. On the infusion times, I'll give a couple of examples that I think very nicely illustrate that because clearly, DARZALEX has got a marvelous improvement for patients, not just reduction in infusion time, but also infusion-related reactions. But if we look at two examples, I'll use Herceptin, where in Europe, that was launched and had several years on the market before biosimilars. As an IV, that was about 30 to 60 minutes.

As a subcu, it was five minutes. In that case, it got to 60% share of sales conversion in just three years. We're seeing a very similar picture, I think, with Phesgo. Slight difference where the IV can be as much as 2-2.5 hours. The subcu is more in the range of five to seven minutes. But again, a very nice global conversion. As I mentioned on the call, already 40% conversion, very close to that, in the 46 launch countries, and certainly showing strong adoption with 40% of sales also coming from the United States now. And so I think those are two examples that say a reduction in time from an hour-long IV to a 5-minute subcu is very attractive in the market. It helps the patient. It reduces healthcare costs.

I think in the world, we're not just outside the U.S., but in the U.S., we're also seeing major infusion suite capacity constraints. There is a growing desire and need to be able to have more patients throughput. The subcu is fitting very well into that in the U.S. and outside the U.S., which is why I think we're seeing such nice growth of Phesgo in all regions of the world.

Mohit Bansal (Equity Research Analyst)

Got it. Super helpful. Thank you, Helen.

Operator (participant)

Your next question comes from the line of Mitchell Kapoor with H.C. Wainwright. Your line is open.

Mitchell Kapoor (Director and Senior Biotechnology Analyst)

Hey, everyone. Thanks for taking the question. I wanted to ask a little bit about your expectations for any kind of coverage barriers with the next launch of subcutaneous versions of products. I guess whenever I think about Tecentriq, the impressive 18% conversion in the first quarter of launch in the U.K. is great, but I'm wondering more broadly, do you see any kind of pushback from payers whenever you're thinking about the next products coming to launch?

Helen Torley (President and CEO)

Yeah. Mitch, on that, we can look to the history as what's happened with all of the products that have been launched. And we always think about these things as outside the U.S. and then inside the U.S. I think outside the U.S., the payers in Europe, in particular, recognize the importance of subcu for reducing the cost of care. And there tends to be very robust adoption. Indeed, sometimes a mandated conversion to subcu because of the very beneficial impact on patients and the healthcare system. So would not presume any barriers at all outside the U.S. In the U.S. as well, there is always a period, which we usually model as about six months, where you do need to get the reimbursement in place. There's automatic coverage in Medicare, but physicians like to wait for the J-code, which is now issued quarterly.

So as an example, after six months, VYVGART HYTRULO got theirs. But once that J-code is in place, the confidence in reimbursement increases. And so I would say just think about it as a little bit of a slow uptake for the first six months and then no real barriers. Same is true with commercial coverage. In general, our partners have priced the IV and the subcu certainly on a WACC basis similarly. And I imagine there's also similar in-market prices to the payers. And while that continues to happen, we hear and see that access is very similar achieved for the IV and subcu. So no barriers there. You could believe that there is even an opportunity with some thoughtful strategies to have subcu be preferred given some of the healthcare costs. And that's certainly something we're thinking about.

We're beginning to talk about with payers and also talk about with some of the government payers as well because subcu offers so many benefits to the healthcare system. So equal playing field today, maybe you can move to a more preferred playing field in the U.S. in the future.

Mitchell Kapoor (Director and Senior Biotechnology Analyst)

Okay. Great. Thank you very much.

Operator (participant)

Your next question comes from the line of Jason Butler with JMP Securities. Your line is open.

Jason Butler (Managing Director of Biotechnology Equity Research)

Hi. Thanks for taking the questions. Two from me. Just following on from the comments around Horizon, is there now an opportunity to see for IGF-1R in thyroid eye disease a new exclusive license with a new party, or is it only a non-exclusive license that becomes available with the termination of the Horizon partnership? And then second question is, can you speak to partnership interest on ENHANZE alone versus ENHANZE plus any Antares auto-injector at this point? Thank you.

Helen Torley (President and CEO)

All right. With the ending of the agreement with Horizon, we actually are in a position to license the IGF-1 target exclusively or non-exclusively, depending on partner need and interest. So we can do either, Jason. On the conversations we're having today, I would say there's an equal weighting of interest in ENHANZE and the high-volume autoinjector. And really, the balance is depending on the volume of expected drug. If it's a drug that's more than 10 ml, clearly, we're focused on just ENHANZE. But we've got some interesting conversations with drugs that are more in that 2-10 ml, and that's where the conversation focuses on the combination of ENHANZE and the high-volume autoinjector.

Jason Butler (Managing Director of Biotechnology Equity Research)

Okay. Great. Thank you.

Operator (participant)

Your next question comes from the line of Joe Catanzaro with Piper Sandler. Your line is open.

Joe Catanzaro (Director and Senior Biotech Equity Analyst)

Hey, everybody. Thanks for taking my question. Maybe just had one quick one on Takeda's IVIG portfolio. And I guess I was wondering how we should think about HYQVIA's historical royalty contribution and then sort of the potential impact it may or may not see with the CIDP label expansion. And I guess I'm asking that because I recall seeing somewhere that CIDP is an indication where IVIG sees the most use. So any comments there would be helpful. Thanks.

Helen Torley (President and CEO)

Yeah. We continue to see growing royalty contribution to Halozyme from sales of HYQVIA. So Takeda has certainly continued to execute and see growing adoption in the area of primary immune deficiency. I agree when we look at the market of use of IVIGs, 20%-25% is reported to be in CIDP. So it certainly is a high-use area. It's an area where patients stay on therapy for a prolonged period of time. And we certainly would expect that the addition of this indication, not just in Europe, but also in the U.S., will offer new growth opportunity upon approval, sorry, for the HYQVIA. I think you also wanted to talk about the new 20% version. That's obviously still in development. And we are very excited to be advancing that. It's in phase III development with Takeda.

We're looking forward to working with Takeda to get that to approval as well and get it used in as many indications as possible.

Joe Catanzaro (Director and Senior Biotech Equity Analyst)

Okay. Thank you. That's helpful. Thanks for taking my question.

Operator (participant)

Your next question comes from the line of David Risinger with Leerink Partners. Your line is open.

Jason Zhuang (Equity Research Associate)

Hi. This is Jason Zhuang for Dave. Thank you for taking my questions. So regarding the long-term projections from your January presentation, could you please provide some perspective on the forecast of annual collaboration revenue of $130 million-$160 million, including key drivers and expected contributions?

Helen Torley (President and CEO)

Yep. I will ask Nicole to address that.

Nicole LaBrosse (Senior VP and CFO)

Yeah. So looking at those projections where we have an annual collaboration revenue of $130 million-$160 million, the drivers are coming from several contributions from our partnerships, one of them being development milestones. So as our partners move through clinical stages, we receive milestones as those targets are achieved. We also have regulatory, registrational, first commercial sales-based milestones, and then continuing sales-based milestones post-launch of a product. We also included within that range $30 million-$60 million. That is related to our expectation of achieving new collaborations and new study starts, new programs progressing through the clinic. So that is the pieces that make up that collaboration revenue.

Jason Zhuang (Equity Research Associate)

Okay. Thanks so much. Very helpful.

Operator (participant)

Once again, if you have a question, it is star one. Your next question comes from the line of Corinne Johnson with Goldman Sachs. Your line is open.

Corinne Johnson (Managing Director)

Yeah. Good afternoon, everyone. Maybe just a question for me on the nature of the autoinjector partnership conversations. What are some of the key questions that your potential partners are asking, and where do you think they're kind of the most comfortable versus where are there any sort of consistent sticking points that you can help them work through?

Helen Torley (President and CEO)

Yeah. I would say, obviously, we always start, and so it's not a question, but one of the important things we always communicate is the long-track record of success and the multiple approvals our platform has attained, Corinne. And Halozyme has delivered over 40 million devices to partners and in use ourselves. So that long-track record of success and the track record of approvals of drug-device combinations is pretty much unmatched, we believe, in the industry. So we always start by making sure they understand that we just have an incredible experience base. We then go on to talk about the fact that our high-volume injector is based on an extrapolation of this already approved and highly reliable base autoinjector.

And again, that is a source of, I think, that pleases them to hear that, that this is something that is tried and tested because what we understand is that there have been some particularly on-body injectors that have been tried over the last several years that have not delivered with the reliability that was required. And so that is a question that they have really on reliability, wanting to be sure that this is going to be able to be delivering for the patient every time. And of course, that's another of the advantages of our Antares' platform is that it is tested to the highest levels of reliability for several of our products like the EpiPen. It's called the five nines reliability, but it's 99.999% fire on time and well.

And so the biggest thing is just helping them understand this is built on an incredible background platform with great experience from our engineers, track record of success with regulators. I think the team has done over 20 human factors studies very successfully also to support regulatory filings. Getting them to understand that, I'd say that is a large focus of the conversation. Then I mentioned in December, and I think it's still true, these are scientists, these are engineers. They want to have a chance to hold and test the device themselves. And so that's what we're doing. We're delighted to announce that one of our partners is advancing in this human factors test on usability. And I think we're going to continue to see that as we are talking to partners. So that, I think, Corinne, would be how I would address that question.

Corinne Johnson (Managing Director)

Great. That was really helpful and comprehensive. And then maybe one more from me. It's been a couple of years since you did the Antares acquisition. How are you thinking about the fit for that commercial business within the broader portfolio? Is this still something you think makes sense strategically?

Helen Torley (President and CEO)

Yeah. When we did the acquisition, we talked about the commercial business as bringing a diversification over revenue. And as Nicole and I both talked about in the call, last year, we achieved $100 million and turned EBITDA positive at the end of the year. So beginning this year, XYOSTED, the leading commercial product, is going to be contributing to EBITDA. And as we talked about in January, it's projected to exceed $150 million in EBITDA contribution by 2028. And so it is a great fit from the point of view of adding to our revenue, diversifying our revenue, but also contributing meaningful EBITDA even on our very large revenue base that we project in 2028. So that's how we view it in terms of the strategy fit.

It is also a wonderful demonstration of the effectiveness and reliability of our small-volume autoinjectors because recall, XYOSTED is a once-a-week, eight-second subcutaneous testosterone replacement that is virtually painless. And so it's a very good thing for us to demonstrate our effectiveness in managing and delivering autoinjectors, but also the high reliability of our device. So lots of strategic fit for it.

Corinne Johnson (Managing Director)

Okay. Great. Thank you.

Operator (participant)

There are no further questions at this time. This will conclude today's call. We thank you for joining. You may now disconnect your lines.