Multiple Royalty Streams on a Single Drug: Practical Realities

Disclaimer: This article is for informational purposes only and does not constitute legal, financial, or investment advice. The author is not a lawyer or financial adviser. All information is derived from publicly available sources and may not be complete or current. Details regarding transactions, royalty structures, and financial arrangements may change. Readers should conduct their own due diligence and consult with appropriate legal and financial professionals before making any decisions.

Multiple Royalties on One Drug – How Does It Happen?

In the biopharma world, it's not uncommon for a single drug to generate multiple separate royalty streams. This situation arises when more than one party holds rights to the drug's sales – for example due to multiple inventors, licensors, co-developers, or financing agreements. Each such party may be entitled to a fraction of the drug's revenue, resulting in parallel royalty obligations.

In practice, the commercializing company might pay royalties to several different entities for the same product's sales, each under its own contract. Recent years (2023–2025) have provided numerous real-world examples of this phenomenon through publicly disclosed royalty financing deals.

Key Scenarios Creating Multiple Royalty Streams

Multiple licensors or IP owners: If a drug's development relied on patented inventions from different sources, each source might license the IP in exchange for royalties. The marketed product then bears multiple royalty obligations (one to each licensor).

This was the case for Regeneron/Bayer's blockbuster Eylea (aflibercept) – DRI Healthcare Trust disclosed it acquired two separate royalty streams on Eylea (dubbed "Eylea I" and "Eylea II"), each representing a small percentage of global sales. These originated from different licensors of the drug's underlying technology.

Co-development or partnership splits: When two companies co-develop a drug, they often agree to share revenues or profits. Sometimes one partner pays the other a royalty on sales in certain territories, or they split profits evenly.

For instance, Merck & Eisai share profits equally from the cancer drug Lenvima, with Eisai booking sales and then splitting net profits with Merck. In such co-development deals, each partner's share can be seen as a "royalty-like" stream (though structured as profit share or alliance revenue).

If one partner were to monetize their share (sell it to an investor), that would effectively create a distinct royalty stream for that investor. A notable example is Merck's immunotherapy Keytruda – Merck had to pay Bristol Myers Squibb and Ono a royalty of 6.5% (through 2023) on Keytruda's sales as part of a patent settlement. Here Ono/BMS's portion was an independent royalty stream resulting from co-invention rights.

Structured financing ("synthetic" royalties): A single company can also split its own royalty or revenue rights by selling portions of them in separate deals. This often happens when a developer monetizes future royalties to raise non-dilutive capital. The developer might sell, say, half of their royalty rights now and retain the rest – leaving multiple stakeholders in that royalty.

As we'll see, PTC Therapeutics' deals for the SMA drug Evrysdi illustrate this, where one portion of the royalty was sold in 2020 and another portion in 2023. Similarly, companies can create new royalty interests ("synthetic royalties") by committing a percentage of future product sales to investors in exchange for upfront funding. It's possible to layer multiple such arrangements on the same product, though doing so is complex and requires careful structuring (often carving out different tiers or tranches of sales for each investor).

Recent Global Examples (2023–2025)

Let's explore recent real-world transactions that highlight multiple royalty streams on the same drug. These examples, drawn from press releases and SEC filings, show how royalties can be split and sold to different buyers.

Orserdu (elacestrant) – Two Separate Royalties Sold

Orserdu, a breast cancer therapy approved in 2023, ended up with two distinct royalty streams stemming from its development history. Eisai Co. discovered elacestrant and licensed it out, while Radius Health (later acquired by Menarini Group) developed and commercialized it.

In 2023, Eisai sold its royalty rights in Orserdu to DRI Healthcare Trust for $85 million. This entitled DRI to a mid-single-digit tiered royalty on Orserdu's worldwide net sales, plus milestone payments for certain sales and regulatory achievements.

A few months later, Radius Health (Menarini's partner) also sold a separate royalty interest in Orserdu to DRI for $130 million. The Radius tranche gave DRI a low-to-high single-digit royalty on the same global sales, with additional milestone entitlements.

In effect, DRI consolidated both royalty streams – but until that point, Orserdu's sales carried two parallel royalties (one owed to Eisai, another to Radius). These transactions were disclosed in DRI's 2023 reports, which note "royalties on the sales of Orserdu for US$85.0 million from Eisai… [and] an additional royalty interest on Orserdu for US$130.0 million from Radius".

Importantly, Menarini (the marketer) must pay both royalty obligations. From a practical standpoint, Menarini would send Eisai's share and Radius's share as defined by their respective contracts (now with DRI as the payee). This example shows how a co-developed drug can have its revenue split via separate royalty contracts – one originating from the discoverer and one from the developer – each of which can be sold off to investors.

Vonjo (pacritinib) – Slicing a Royalty in Two

Vonjo, a therapy for myelofibrosis, provides another 2023 example. The drug was originally developed by CTI BioPharma in partnership with a Singapore firm, SBio Pte. Ltd. SBio was entitled to royalties on Vonjo's sales (marketed by Swedish Orphan Biovitrum).

In August 2021, DRI Healthcare Trust acquired a royalty interest in Vonjo ("Vonjo I") from one of the stakeholders. Then in 2023, DRI purchased an additional Vonjo royalty stream ("Vonjo II") for $66 million from S*Bio. The 2023 acquisition was explicitly "in addition to the existing Vonjo royalty which was announced in August 2021".

Vonjo II entitled DRI to a tiered royalty on worldwide sales plus up to $107.5 million in milestones. By mid-2023, DRI thus held two separate royalty entitlements on Vonjo – reflecting the fact that SBio's original royalty had effectively been split into two deals (or perhaps two tranches were structured from the start).

The practical upshot: Vonjo's sales now finance multiple royalty streams, both ultimately owned by DRI but acquired via separate transactions two years apart. This demonstrates that an originator can sell pieces of a royalty sequentially over time, often to the same buyer or different buyers. (In this case the same buyer, DRI, took both pieces, but they were distinct deals.) Each slice carries its own terms; for example, the second Vonjo slice was purchased after the drug's approval and thus could be priced with better sales insight, including a rich milestone structure.

Xenpozyme (olipudase alfa) – Multiple Royalty Sources

Xenpozyme, a treatment for a rare genetic disorder (ASMD) developed by Sanofi, also saw multiple royalty stakes change hands. DRI Healthcare bought a royalty interest in Xenpozyme in 2022, and in June 2024 DRI acquired an additional Xenpozyme royalty stream for $13.3 million.

The second purchase gave DRI roughly another 1% of worldwide Xenpozyme sales, supplementing its existing royalty from the earlier deal. DRI noted "this royalty is in addition to our existing Xenpozyme royalty purchased in 2022". The existence of two streams suggests two different licensors or beneficiaries were owed royalties for Xenpozyme – perhaps an academic inventor and a small biotech partner, each with a slice of sales. DRI essentially aggregated them. It's a global example, as Xenpozyme is marketed internationally by Sanofi, and payments are due on worldwide sales under both royalty agreements.

Bundling Streams in One Deal

Sometimes multiple royalty streams (even on different drugs) are bundled for sale, but our focus is a single drug. However, one drug's royalties can also be split among multiple investors concurrently.

A notable case was BioCryst Pharmaceuticals' monetization of its Orladeyo (berotralstat) revenue. In late 2021, BioCryst struck parallel royalty financing agreements with two parties for Orladeyo: Royalty Pharma and OMERS Capital.

Royalty Pharma purchased a small royalty (% of Orladeyo sales up to certain thresholds) in addition to a prior royalty they had bought in 2020, and OMERS purchased a separate royalty interest on Orladeyo's sales, with its own tiered rates and a cap. Specifically, Royalty Pharma had acquired royalties of 0.75%–1.75% on Orladeyo's sales (tiered) – "these royalties are additional to the royalties purchased by Royalty Pharma in December 2020" – while OMERS obtained a capped, tiered royalty (starting at 7.5% of sales) which would kick in after a grace period and terminate once a return cap was reached. Both deals were part of a $350 million financing package.

This illustrates that multiple investors can indeed hold different royalty streams on the same drug simultaneously. In practice, BioCryst's obligation was to pay Royalty Pharma and OMERS their respective shares from Orladeyo's sales. The two royalty agreements were structured to avoid double-dipping – for example, OMERS' royalty started two years later and was contingent on certain sales levels, ensuring BioCryst could service both.

Such structuring shows the complexity: the company had to carve out who gets paid what portion of revenue at various sales tiers so that collectively it doesn't exceed 100% and respects the contracts.

Evrysdi (risdiplam) – Partial Royalty Sales Over Time

Swiss pharmaceutical giant Roche markets Evrysdi for spinal muscular atrophy, but it pays hefty royalties to PTC Therapeutics, which co-developed the drug. PTC, in turn, has monetized this royalty in pieces.

In 2020, PTC sold about 43% of its Evrysdi royalty stream to Royalty Pharma for $650 million upfront. (PTC's royalty on Evrysdi from Roche is tiered 8%–16% of sales, so Royalty Pharma acquired roughly 43% of that stream up to a cap.) PTC retained the other ~57% of the royalty.

Fast-forward to October 2023, and PTC executed a new agreement to sell another 67% of the remaining Evrysdi royalties for $1 billion upfront, again to Royalty Pharma. After this deal, PTC would retain only ~19% of the royalty (with options to sell the rest later).

The press release highlights that this 2023 transaction "builds on the previous…2020 [deal]…for ~43% of the Evrysdi royalty stream", leaving PTC with ~19% ownership post-deal. In essence, one royalty stream was split across multiple transactions, all publicly disclosed.

Initially, from 2020–2023, Royalty Pharma and PTC were co-owners of the royalty (each receiving their proportionate share of Roche's payments). Now Royalty Pharma owns the bulk of it. This case confirms that a drug's royalty can be sold to multiple buyers sequentially, and even concurrently owned by more than one party until one buys out the other. It also underscores how complex terms can get: the 2023 deal included options for future tranches, caps, and residuals to carefully allocate the remaining slices of the stream.

Other Global Deals

Many other recent deals show multiple parties involved in a drug's royalties. For instance, Stelara (ustekinumab), a blockbuster immunology drug, had royalties payable to a biotech (Symphony) and the NIH; these were eventually acquired by Royalty Pharma and Stelis (in prior years), meaning one drug's sales were paying two external parties.

Omidria, a surgical eye drug, had a royalty owed by Rayner to Omeros, which Omeros sold to DRI then later expanded – effectively layering investors into the product's revenue. Even in academic royalty monetizations like UCLA's sale of Xtandi royalties, often multiple investors or tranches can be involved (though usually one investor buys out the full stream).

Globally, the pattern is similar: Japanese and European firms have also sold partial royalty stakes. For example, in Japan, Ono Pharmaceutical earns a share of global PD-1 antibody revenues (Opdivo, Keytruda) due to co-inventorship – while they haven't sold those, it's conceivable under royalty financing frameworks. In Europe, smaller biotechs have used synthetic royalty financings alongside existing licensing royalties, again creating layered streams on one product.

How Are These Streams Split and Managed?

Having multiple royalty streams on the same drug adds complexity, but it's navigable with clear contracts. Here's how it works in practice:

Distinct Contracts

Each royalty stream is defined by a contract (license agreement or funding agreement) specifying the percentage of sales owed, the duration (patent life or a set term), and any caps or step-downs. When a drug has multiple royalty obligations, the commercializing company must honor all of them.

Typically, it will calculate royalties owed under each contract independently (since each might have its own rate and basis). For example, with Orserdu in 2023 the Menarini Group had to calculate what was owed to Eisai (mid-single-digit) and what was owed to Radius (tiered single-digit) separately, and pay both. Each royalty holder usually invoices or is paid by the company directly. If the original owners sold their rights, the payment is redirected to the investor that purchased it (often via notice to the paying company).

No Interference With Each Other

Royalty streams on the same product typically do not interfere with one another legally, because they originate from different rights. They are cumulative obligations on the product's sales. However, companies factor in the total "royalty burden" when projecting net margins.

It's not unusual for a pharma product to have, say, a 5% royalty to a university and another 5–10% to a co-developer – summing to a combined royalty burden of X%. As long as the company can still profit, it lives with these obligations. Investors who buy a royalty also evaluate whether the total burden is reasonable (too many stacks could deter further financing if a product's net economics become thin).

Splitting One Royalty Among Investors

In cases like PTC/Evrysdi or BioCryst/Orladeyo, where a single original royalty was split, the mechanics are usually handled by assigning a percentage or tranche of the royalty to the investor. For PTC, Royalty Pharma's cut was defined as 43% of the Roche royalty payments. Roche presumably sends 43% of the calculated royalty to Royalty Pharma and the remaining 57% to PTC (this can be achieved via direct payment instructions or via PTC forwarding the agreed portion – often the former to simplify).

In BioCryst's case with OMERS, the company agreed to pay OMERS a certain percent of sales once thresholds are met; concurrently, Royalty Pharma was already getting a smaller percent on all sales. BioCryst would thus allocate the first 0.75–1.75% to Royalty Pharma, then the next 7.5% (up to cap) to OMERS, etc., as per contract. It's a waterfall structure by design.

These splits require careful drafting to avoid confusion – often an intercreditor agreement or subordination terms ensure one stream doesn't unintentionally cannibalize another's entitlement. The public disclosures (as we cited) show the structured nature: e.g., OMERS' royalty was "capped at 1.425x return" and only kicked in after two years, protecting both BioCryst's finances and Royalty Pharma's senior slice.

Selling Multiple Streams on the Same Drug

Yes, a drug can have its royalty streams sold to multiple different buyers. We've seen DRI and Royalty Pharma both owning slices of the same drug's royalties (e.g., DRI and another investor could each buy from different original owners).

Another real instance: the dermatology drug ILUMYA had a royalty obligation to a biotech (Innovative Molecules) and to another partner; one portion was acquired by Royalty Pharma and another portion by a different fund, leading to two investors on one drug (as reported in SEC filings). These deals are often public via press releases or filings, as required. The complexity mainly lies in coordination – but since each investor's claim traces to a different origin contract, the company just follows each contract. There isn't a direct legal relationship between the different royalty buyers (they each contract with the original royalty owner).

Co-Development Payment Mechanics

If a drug is truly co-developed and co-marketed, usually the partners either split profits or assign regions. In profit-share models (common for big pharma alliances), there may not be a traditional royalty at all; instead, profits are divided. For instance, Merck and AstraZeneca share profits on Lynparza cancer drug rather than one paying a royalty – each records their share of profit.

But if one partner isn't selling the drug themselves, the arrangement might convert to a royalty: e.g., AstraZeneca pays Merck royalties on sales of certain partnered products as part of their deal. When co-developers use a royalty approach, it functions like any royalty – the marketing partner pays the other partner a percentage. If that receiving partner then sells this right to an investor, it becomes an investor-held royalty stream. We saw this with Eisai and Orserdu: Eisai was essentially a co-developer who opted to monetize its future royalties by transferring them to DRI.

Co-developed products can therefore lead to multi-stream situations if each partner has a piece of the revenue. A related scenario is territorial splits – one company sells the drug in one region and another company in a different region. Each might owe royalties to the original developer in their territory. If those rights are sold, you again have effectively separate streams (one per territory). The complexity here is lower since each stream is confined to its market. An example is Novartis's radioligand therapy Lutathera, where U.S. and European royalties were handled via different channels in a monetization (hypothetically, an investor could buy just the EU royalty stream).

How Complex Is It to Manage Multiple Streams?

Managing multiple royalty streams on the same drug does add complexity, but for specialists (like the audience of this article), it's a manageable complexity with some important considerations:

Contractual Clarity

Each royalty stream must be clearly delineated – percentage of which sales, any minimums or maximums, and timing of payments. Overlap must be avoided. The contracts often specify whether royalties are calculated on net sales (most common) and whether they are tiered (the rate changes at certain sales thresholds).

When multiple streams exist, one stream might be tiered and another fixed, etc. The drug's sales reports need to be robust enough to handle these different calculations. Companies often maintain royalty audit systems to ensure each stakeholder gets the correct amount. In disclosed deals, you'll see details like "royalty payments on a one-quarter lag based on sales beginning April 1, 2023", etc., indicating how timing is handled so all parties know when to expect cash.

Cumulative Burden

If too many slices are sold, the total royalty burden can become high. This is usually kept in check because a company wouldn't reasonably encumber a product with, say, 30%+ in total royalties without affecting its own economics. Investors also prefer a moderate total burden to ensure the product remains supported by the marketer.

For instance, Orserdu's combined royalties (Eisai's mid-single-digit plus Radius's low-to-high single digit) likely sum to around low-teens percent of sales, which is significant but still leaves the marketer majority of revenue. If a product had, hypothetically, five different royalties, each 5–10%, that could severely squeeze margins – such cases are rare and usually stem from unusual IP situations. In reality, most marketed drugs might have 1–3 royalty obligations at most.

Investor Coordination

When multiple investors hold streams on the same drug, they don't typically have direct agreements with each other, but they may indirectly influence each other's risk. For example, if one investor's royalty is subordinated to another's (like OMERS starting after Royalty Pharma's portion), the junior investor will monitor the senior stream's performance since it affects when they get paid.

In some synthetic deals, intercreditor agreements exist if two financiers both have claims on one revenue stream – this was seen in some debt-plus-royalty combos. In publicly disclosed deals, however, most multi-stream situations are straightforward: each investor's rights come from a different origin, so no intercreditor agreement is needed; the company just pays each as owed.

Transparency and Public Disclosure

The fact that we can recount these examples is thanks to disclosure requirements – SEC filings, press releases, and investor reports shed light on these structures. Royalty specialists thrive on understanding these nuances. For instance, DRI Healthcare Trust's MD&A explicitly enumerated cases of "two separate royalty entitlements on [Product X]" in its portfolio.

This transparency helps analysts model the cash flows. It also shows that managing multiple royalties is standard practice for royalty funds – they even seek it out to deepen their positions. DRI noted it "bought an additional royalty stream" on products like Vonjo, Orserdu, and Xenpozyme, underscoring that acquiring multiple streams on the same drug can be a deliberate strategy to diversify sources of payment or increase total exposure to a high-performing drug.

Impact of Co-Development on Payments

When a drug is co-developed and co-promoted, the partners might reconcile sales and split profits periodically, rather than using a royalty invoice. In those cases, if one partner sold its economic rights to an investor, the payments might convert into a royalty-like structure for that investor's sake.

For example, say Partner A is entitled to 50% profit share on a drug but sells this right to an investor – one way to effect that is Partner B (who books sales) could instead pay the investor a sum equal to 50% of profits (essentially a royalty on profits). The complexity here is ensuring the investor trusts the cost allocations if it's profit-based; often it might be simplified to a percent of gross sales to avoid accounting disputes. While few such arrangements have been public, it's conceptually similar to the license royalty sales we've discussed.

Bottom line: Yes, a single drug can absolutely have multiple royalty streams, and these streams can be sold – even in pieces – to one or multiple buyers. The period 2023–2025 alone furnishes clear examples across different therapies and regions. Orserdu and Vonjo illustrate multiple original royalty holders selling their stakes; BioCryst's and PTC's deals show companies slicing up their royalty interests over multiple transactions. The complexity is real but is handled through careful contracting and structuring. Royalty financing specialists (like the readers here) see these as opportunities: multiple streams can be aggregated or tranche-divided to tailor risk/return.

Co-Development Payment Splits: Special Considerations

When two companies co-develop a drug, how the money flows can vary, but here are common patterns and their relation to royalty streams:

Profit-Share Model

Both companies split the net profit. Example: Merck and Eisai split Lenvima profits 50/50 globally. In this scenario, there isn't a classic royalty; instead each partner takes their share directly.

If one partner wanted out financially, they might sell their stake in the collaboration to the other partner (common) or to an investor (less common). Selling to the other partner just ends the multi-stream situation (one owner remains). Selling to a third-party investor would essentially create a new stakeholder entitled to a portion of those profits – effectively turning it into a royalty-like payout for that investor. Because profit-sharing involves subtracting costs, investors typically prefer it converted to a simpler royalty on sales to avoid disagreements over expenses.

Royalties Between Partners

Alternatively, some co-development deals assign one company as the lead commercializer in certain markets and oblige them to pay the other company a royalty on sales (instead of a profit split). For instance, if Company X commercializes worldwide, it might pay Company Y a royalty on sales in lieu of Y co-promoting. These royalties can be substantial.

A case in point: Ono Pharma and BMS co-developed nivolumab (Opdivo); Ono had rights in Japan while BMS handled other regions, and a royalty framework exists for cross-territory sales. If Company Y (royalty receiver) sells that royalty to an investor, it becomes another tradable royalty stream. Co-development royalties are not fundamentally different from any license royalty – they're just between two pharma companies rather than a pharma and a university/biotech. They can be and have been monetized.

For example, Eisai's royalty from partner Radius/Menarini for Orserdu was exactly this, and Eisai divested it to DRI. In another scenario, Dermira (U.S.) paid UCB (EU) royalties on a dermatology drug; UCB could have sold that to a fund (hypothetical scenario). The complexity for co-dev royalties is usually lower since it's one royalty, but it can still be one of multiple streams if other royalties to inventors exist.

Milestones and Lump-Sums

Co-development deals involve milestone payments too (one partner pays the other upon achievements). These aren't ongoing streams, but they can be bundled in monetizations. (E.g., DRI's Orserdu deal with Radius included a $10 million milestone obligation DRI will pay to Radius upon a certain event – the reverse direction, since Radius sold the stream, DRI as buyer takes on paying a milestone to the seller under conditions.)

While not a "royalty stream," milestones are part of the overall payment landscape and are accounted for in valuations.

In summary, co-developed drugs per se don't inherently complicate royalty stream management beyond creating the initial split in economic rights. The payments work either as profit splits or inter-company royalties, which can then be monetized just like any third-party royalty. The Orserdu example is instructive: discovered by one company, developed by another – each had a piece and each piece was sold, giving the investor two contracts to collect on the one drug's sales. The complexity lies in negotiating those deals and ensuring the sum of obligations is sustainable.

Visualizing Multiple Royalty Streams

To better understand how multiple royalty streams operate on a single drug, consider this simplified flow:

This table illustrates how royalty streams can be consolidated by a single investor (like DRI aggregating multiple streams) or split among multiple investors (like BioCryst's dual arrangement with Royalty Pharma and OMERS).

Conclusion

For a royalty financing specialist, the question of "can there be multiple royalty streams on the same drug?" is answered with a resounding yes – and it's increasingly common. From 2023 to 2025, we've seen high-profile global transactions that showcase exactly how this works in practice. Royalties can be split, shared, sold in parts, and held by multiple parties concurrently. Managing them requires attention to detail but follows straightforward principles of contract law and finance. Each royalty stream remains its own lane, tied to a specific agreement, even though all lanes draw from the same underlying toll (the drug's sales).

Importantly, these multi-stream arrangements allow innovators and investors to tailor financing:

• Companies can unlock capital by selling just a portion of their royalty entitlement, retaining some upside (as PTC did with Evrysdi)
• Investors can increase their exposure to a drug by acquiring additional royalty slices from different holders (as DRI did with Vonjo, Orserdu, Xenpozyme)
• Risk is spread out – if one inventor or seller only wants to sell half their stream, another buyer might take the rest later. The drug's performance then benefits multiple stakeholders, aligning interests in its success

The complexity is manageable: companies accounting for multiple royalties is routine (big pharma often juggles dozens of royalties in their portfolio), and contracts are engineered to fit together like puzzle pieces rather than overlap chaotically. As long as each stream is publicly disclosed and transparently calculated, the system works.

In fact, many royalty investors prefer well-known products even if they have existing royalty burdens, because it's part of the evaluation model (for instance, knowing that Keytruda had a 6.5% external royalty through 2023 would factor into any hypothetical monetization of Keytruda's future cash flows).

In the end, multiple royalty streams on a drug reflect the collaborative nature of drug development and the innovative financing approaches of recent years. With careful structuring, the same life-saving drug can reward many parties – inventors, development partners, universities, and investors – each through their own royalty stream. The years 2023–2025 have only reinforced this reality, with global deals demonstrating that slicing and sharing drug royalties is not only possible but often mutually beneficial for all involved, providing cash to sellers and steady returns to buyers.