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LIGAND PHARMACEUTICALS INC

For the period ended Dec 31, 2024. Filed Feb 28, 2025.

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A company's yearly report to the SEC, with audited financial statements. It is the fullest account a company gives of its business, its finances and the risks it sees.

FY2024 · Filed Feb 28, 2025

LGND$314.16+0.0%Stored close · as of Nov 10, 2026

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Item 1. Business

PART I

Cautionary Note Regarding Forward-Looking Statements:

You should read the following report together with the more detailed information regarding our company, our common stock and our financial statements and notes to those statements appearing elsewhere in this document.

This report contains forward-looking statements, as defined in Section 21E of the Securities Exchange Act of 1934, as amended, that involve a number of risks and uncertainties and reflect Ligand’s judgment as of the date of this report. Although our forward-looking statements reflect the good faith judgment of our management, these statements can only be based on facts and factors currently known by us. Consequently, these forward-looking statements are inherently subject to risks and uncertainties, and actual results and outcomes may differ materially from results and outcomes discussed in the forward-looking statements.

All statements contained herein, other than statements of historical fact, could be deemed to be forward-looking statements. In some instances, forward-looking statements can be identified by the use of forward-looking words such as “believes,” “expects,” “may,” “will,” “plan,” “intends,” “estimates,” “would,” “continue,” “seeks,” “pro forma,” or “anticipates,” or other similar words (including their use in the negative), or by discussions of future matters such as those related to our future results of operations and financial position, royalties and milestones under license agreements, Captisol material sales, product development, and product regulatory filings and approvals, and the timing thereof, Ligand's status as a high-growth company, as well as other statements that are not historical in nature. You should be aware that the occurrence of any of the events discussed in Part I under Item 1A under the caption “Risk Factors” of this report could negatively affect our results of operations, financial condition and the trading price of our stock.

The cautionary statements made in this report are intended to be applicable to all related forward-looking statements wherever they may appear in this report. We urge you not to place undue reliance on these forward-looking statements, which reflect our good-faith beliefs (or those of indicated third parties) and speak only as of the date of this report. Except as required by law, we disclaim any intent or obligation to update these forward-looking statements beyond the date of this report, even if new information becomes available in the future. This caution is made under the safe harbor provisions of Section 21E of the Securities Exchange Act of 1934, as amended.

References to “Ligand Pharmaceuticals Incorporated,” “Ligand,” the “Company,” “we,” “our” and “us” include Ligand Pharmaceuticals Incorporated and our wholly-owned subsidiaries.

Partner Information

Information regarding partnered products and programs comes from information publicly released by our partners and licensees.

Trademarks

This Annual Report on Form 10-K includes trademarks, trade names and service marks owned by us. Ligand®, BEPro™, Captisol®, CyDex®, LTP®, LTP Technology®, NITRICILTM, and ZELSUVMITMare protected under applicable intellectual property laws and are our property. All other trademarks, trade names and service marks including, but not limited to Pelican Expression Technology®, PeliCRM®, Pfenex Expression Technology®, OmniAb® Kyprolis®, Evomela®, Veklury®, Livogiva®, Bonteo®, Zulresso®, Rylaze®, Vaxneuvance™, Pneumosil®, Minnebro®, Baxdela®, Nexterone®, Noxafil®, Duavee®, Filspari®, Ohtuvayre™, Qarziba®and are the property of their respective owners. Solely for convenience, trademarks, trade names and service marks referred to in this report may appear without the ®, ™ or SM symbols, but such references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or the right of the applicable licensor to such trademarks, trade names and service marks. Use or display by us of other parties’ trademarks, trade dress or products is not intended to and does not imply a relationship with, or endorsement or sponsorship of, us by the trademark or trade dress owners.

Item 1.Business

Overview

We are a biopharmaceutical company enabling scientific advancement through supporting the clinical development of high-value medicines. Ligand does this by providing financing, licensing our technologies or both. Our business model seeks to generate value for stockholders by creating a diversified portfolio of biopharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable and diversified manner. Our business model focuses on funding programs in mid- to late-stage drug development in return for economic rights, purchasing royalty rights in development stage or commercial biopharmaceutical products and licensing our technology to help partners discover and develop medicines. We partner with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) in order to generate our revenue. We operate two infrastructure-light royalty-generating IP platform technologies. Our Captisol platform technology is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Our NITRICIL platform technology facilitates “tunable” dosing, permitting an adjustable drug release profile to allow proprietary formulations that target a broad range of indications. We have established multiple alliances, licenses and other business relationships with the world’s leading biopharmaceutical companies including Amgen, Merck, Pfizer, Jazz, Gilead Sciences and Baxter.

Our revenue consists of three primary elements: royalties from commercialized products, sales of our Captisol material to partners, and contract revenue from license fees and milestones payments.

Strategy and Execution

We are a biopharmaceutical royalty aggregator, focused on investing in differentiated late-stage assets and operating royalty-generating, infrastructure-light platform technologies. Since our transition to this business model in 2007, we have deployed over $1 billion of capital to build our diverse portfolio. In 2022, Ligand made a deliberate decision to focus on an efficient, high margin, low infrastructure version of our historical model. Following the spin-offs of our OmniAb antibody discovery business in November 2022 and the Pelican Expression Technology subsidiary in September 2023, our focus is to continue to expand our pipeline by aggregating royalty rights in mid- to late-stage development and commercial biopharma products, while maintaining a lean infrastructure and high-margin business.

Our business model is highly differentiated from a traditional biotechnology company in several important ways. First, we have limited infrastructure requirements, enabling us to maintain relatively high operating margins. Second, we can enable development over a broad range of therapeutic areas and can be strategic and balanced about the size of our investments to achieve a highly diversified portfolio. Third, our business model mitigates the high volatility and risk associated with building a business around a single or small number of assets. With this approach, we have the ability to mitigate the impact of binary clinical outcomes inherent in the biopharmaceutical industry, thereby facilitating cash flows that are more predictable. Finally, we can target the size of our investments to achieve appropriate risk management across the portfolio.

As an organization, we bring a highly experienced team and financial strength to execute on our strategy. There is high demand for capital and low availability of structured capital in the segment of the biopharmaceutical market in which we operate, creating significant investment opportunities for Ligand. Unlike open-market equity investing, many of our investments take place under Confidential Disclosure Agreements (CDAs), allowing us access to in-depth, advantageous diligence materials. Our flexible investment structures are designed to mitigate risks and help accommodate different transaction structures in line with our partners' goals. We believe our business model is highly scalable and has significant growth potential. We have assembled a talented, long-tenured team with deep industry relationships, investment experience and industry knowledge.

From a more tactical perspective, we execute our strategy using four key approaches: royalty monetization, special situations, project finance, and IP technology platform investments. With royalty monetization, we purchase rights on existing royalty contracts that are owned by inventors, academic institutions or companies. There are advantages of royalty investing as a model since royalties 1) require minimal infrastructure, 2) are non-dilutable and 3) their cash flows are often protected in bankruptcy. In special situations investing, we can acquire or restructure companies with valuable assets or partnerships and realize the value of those assets by incubating and partnering the product assets, or holding preestablished royalty contracts/assets. Ligand has a track record of doing this successfully with investments such as:

Pharmacopeia acquisition in 2008, which yielded Travere’s Filspari

Metabasis acquisition in 2010, which contributed to the creation of Viking Therapeutics

Vernalis acquisition in 2018, which yielded Verona’s Ohtuvayre

Pfenex acquisition in 2020, which yielded five of our major commercial programs – Capvaxive, Vaxnuevance, Rylaze, Pneumosil, and Teriparatide, as well as our equity interest in Primrose Bio

Novan acquisition in 2023, which yielded ZELSUVMI

Apeiron acquisition in 2024, which yielded Qarziba

Project finance involves the provision of development capital to fund late-stage clinical programs in return for royalty contracts that we negotiate, creating synthetic royalties on the future sales of those products. Finally, with IP technology platform acquisitions, we look for platforms that are infrastructure-light with existing royalties in place while providing the potential for new royalties through operating those platforms. Ideal technology IP platforms will be scalable and have broad applicability. Our Captisol and NITRICIL businesses are excellent examples of successful platform technology investments.

We have a specific set of criteria we use to assess potential investments. The first is time to cash flow, as we seek products that are within a few years of regulatory approval and commercialization. Typically, this means we invest in Phase 3 assets, although we also evaluate opportunities to invest from Phase 2 assets to approved assets. In terms of an asset's clinical profile, we are looking for strong data supporting both efficacy and safety, and products which will ultimately deliver significant value to patients and to the healthcare system. We also look for strong market exclusivity, which can be achieved through intellectual property and/or regulatory protections. Structural alignment with our counterparty and the commercial counterparty is also a key criteria of the investments we make. Ultimately, we look for assets with favorable risk-reward profiles, which have above average probability of technical and regulatory success and can be commercialized effectively.

Technologies

Through a combination of research and acquisitions, we have created a partnered portfolio with a wide variety of underlying technologies. This diversification provides the added benefits of exposure to a wider breadth of scientific innovation, more licensing opportunities and lower impact of individual patent expiry.

Captisol Technology

Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. This unique technology has enabled FDA-approved products, including Gilead’s Veklury, Amgen’s Kyprolis, Baxter’s Nexterone, and Acrotech Biopharma’s Evomela. There are many Captisol-enabled products currently in various stages of development. We maintain a broad global patent portfolio for Captisol with the latest expiration date in 2033. Other patent applications covering methods of making Captisol, if issued, extend the expiration date to 2041.

In addition to solid Captisol powder, we offer our partners access to cGMP manufactured aqueous Captisol concentrate. This product offering was established in 2017 to reduce cycle time and increase Captisol production capacity for large-volume drug products. We maintain both Type IV and Type V DMFs with the FDA. These DMFs contain manufacturing and safety information relating to Captisol that our licensees can reference when developing Captisol-enabled drugs. We also have active DMFs in Japan, China and Canada.

NITRICIL Technology Platform

The NITRICIL technology platform was acquired through our Novan acquisition in 2023. This product leverages nitric oxide's naturally occurring antimicrobial and immunomodulatory effects to develop new therapies for unmet medical needs across multiple therapeutic areas. Our nitric oxide platform allows for “tunable” dosing, permitting an adjustable drug release profile to allow proprietary formulations that target a broad range of indications. NITRICIL is currently leveraged in one FDA approved product, ZELSUVMI. Clinical development success positions the NITRICIL platform well for future expansions into other indications.

HepDirect, LTP and BEPro Technology Platform

The HepDirect and LTP technology platforms are our proprietary liver-targeting prodrug technologies that can deliver many different chemical classes of drugs to the liver by using a chemical modification that renders an active pharmaceutical ingredient (“API”) biologically inactive until cleaved by a liver-specific enzyme. These technologies may improve the efficacy and/or safety of certain drugs and can be applied to marketed or new drug products to treat liver diseases or diseases caused by hemostasis imbalance of circulating molecules controlled by the liver.

The BEPro technology platform is a next generation prodrug technology distinct from HepDirect and LTP prodrug technologies, expanding use to non-liver related diseases. BEPro is specifically applicable to nucleotides and nucleotide analogs for the development of compounds with improved product profiles. Ligand has demonstrated benefits in cell penetration and oral, intravenous and inhaled pharmacokinetics with BEPro-enabled nucleotide analogs.

Pelican Expression Technology (owned by Primrose Bio, of which Ligand owns 31.4% as of December 31, 2024)

The Pelican Expression Technology platform is a robust, validated, cost-effective and scalable platform for recombinant protein production and is especially well suited for complex, large-scale proteins. Global manufacturers have demonstrated consistent success with the platform, and the technology is currently outlicensed for multiple commercial and development-stage programs. The versatility of the platform has been demonstrated in the production of enzymes, peptides, antibody derivatives and engineered non-natural proteins. The platform contributes significant value to biopharmaceutical development programs by shortening timelines and reducing costs associated with research and development through commercial manufacturing of therapeutics and vaccines. Given pharmaceutical industry trends toward large molecules with increased structural complexities, the Pelican Expression Technology platform is well positioned to meet these growing needs as one of the most comprehensive and broadly available, commercially validated protein production platforms in the industry.

2024 and Recent Investment Highlights

On February 25, 2025, we announced that we entered into a royalty financing agreement with Castle Creek Biosciences, Inc., a late-stage cell and gene therapy company, to support Castle Creek’s D-Fi (FCX-007) Phase 3 clinical study. D-Fi is an injectable autologous gene-modified cell therapy in development for the treatment of dystrophic epidermolysis bullosa (“DEB”), candidate for the treatment of DEB, a devastating, painful, and debilitating rare genetic skin disorder. Under the terms of the agreement, we have invested $50 million in exchange for a mid-single digit royalty on worldwide sales of D-Fi and a portion of a future milestone payment upon D-Fi achieving FDA approval. An additional $25 million was secured from a syndicate of co-investors in return for a high-single digit royalty on worldwide sales of D-Fi.

Throughout 2024 and into January of 2025, we acquired additional royalties from several Ohtuvayre inventors, bringing our total Ohtuvayre royalty to 3%.

In July 2024, we acquired Apeiron Biologics AG (“Apeiron”), which holds royalty rights to Qarziba (dinutuximab beta) for the treatment of high-risk neuroblastoma in patients aged 12 months and above, for $100 million. In addition, we agreed to pay Apeiron shareholders additional consideration based on future commercial and regulatory events, including up to $28 million if Qarziba royalties exceed certain predetermined thresholds by either 2030 or 2034, and pay additional earn-outs on specific future commercial and regulatory events. Qarziba was approved by the European Medicines Agency in 2017 and is commercially available in more than 35 countries. We receive a tiered mid-teen royalty on sales of Qarziba from Recordati. See “Item 8. Financial Statements and Supplementary Data—Notes to Consolidated Financial Statements—Note (3), Acquisitions.”

In June 2024, following on our first two investments in 2018 and 2023, we invested an additional $2.5M in Palvella in the form of a convertible notes, which upon Pavella's merger with Pieris, converted to common shares of Pavella.

In May 2024, we committed $75 million to a royalty financing agreement (the “Agenus Agreement”) with Agenus intended to support Agenus’ key development initiatives in the ongoing botensilimab and balstilimab (“BOT/BAL”) clinical development program, including a Phase 3 trial in its lead indication of patients with metastatic, relapsed/refractory, microsatellite stable (MSS) colorectal cancer, not microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR), who are without active liver metastases (r/r MSS CRC NLM), along with other launch readiness activities. Under the terms of the Agenus Agreement, we paid $75 million to Agenus at closing. In addition, we have the option to invest an additional $25 million on the same terms on a pro rata basis. In return for our initial $75 million payment, we are entitled to receive 18.75% of future royalties and 31.875% of future milestone payments related to six of Agenus’ clinical-stage oncology programs. For five of these programs the partner has either returned, not exercised a license option or indicated they would no longer pursue development including BMS-986442, AGEN2373, INCAGN2385 and INCAGN2390 and MK-4830. UGN-301 is currently being evaluated in Phase 1 trials in bladder cancer by UroGen Pharma. Additionally, we will receive a 2.625% synthetic royalty on future global net sales generated by BOT/BAL. The royalties and milestone payments owed could be adjusted up or down based upon pre-determined future events and achievement of certain milestones. See“Item 8. Financial Statements and Supplementary Data—Notes to Consolidated Financial Statements—Note (2), Agenus Transaction.”

Novan Acquisition

In September 2023, the Bankruptcy Court approved a $12.2 million bid from Ligand to purchase certain assets of Novan, Inc. (“Novan”), including its lead product candidate berdazimer topical gel, 10.3% (“berdazimer gel”), all assets related to the NITRICIL technology platform and the rights to one development stage asset. Prior to Novan's bankruptcy, we had a royalty interest in berdazimer gel. Berdazimer gel was subsequently approved by the FDA in January 2024, with a brand name of ZELSUVMI.

On April 3, 2024, Ligand announced the creation of Pelthos Therapeutics (“Pelthos”) under the leadership of Scott Plesha as Chief Executive Officer. Pelthos is focused on the commercialization of innovative, safe, and efficacious therapeutic products for patients suffering from conditions with limited treatment options. ZELSUVMI, its first product, is the first and only FDA-approved prescription medicine for the treatment of the highly transmissible molluscum contagiosum (molluscum) viral skin infection in adults and pediatric patients one year of age and older. It is the first and only FDA approved topical prescription medication for this infection that can be applied by patients, parents and caregivers at home, outside of a physician's office, or other medical setting.

ZELSUVMI received a Novel Drug designation from the U.S. FDA in January 2024 to treat molluscum viral skin infection. ZELSUVMI was developed using Pelthos' proprietary nitric oxide-based NITRICIL technology platform. As we incubate this newly acquired business, the Pelthos team is actively preparing for a potential strategic transaction and subsequent commercial launch by mid-2025 of the assets acquired in the Novan acquisition (including ZELSUVMI and other assets that may be developed using the NITRICIL technology platform). Consistent with our business model, we are engaging with potential commercial partners and outside investors to maximize the value of these assets for Ligand stockholders through a licensing or other strategic transaction involving Pelthos. See “Item 8. Financial Statements and Supplementary Data—Notes to Consolidated Financial Statements—Note (3), Acquisitions.”

Commercial and Clinical Stage Partnered Portfolio

We have a large royalty portfolio including 12 major commercial-stage revenue-generating royalty assets and over 75 additional active programs with future revenue-generating potential, including over 85 that are programs that are fully-funded by our partners.

The following table provides an overview of royalty receipts on our commercial-stage revenue-generating royalty assets:

ProductPartnerTherapeutic AreaRoyalty Rate2024 Royalty Receipts (in millions)Estimated 2024 Product Revenue (in millions)
KyprolisAmgen/Ono/BeigeneOncology1.5% - 3.0%$38.4$1,627.4
QarzibaRecordatiOncologyTiered mid-teen$14.6— 1
RylazeJazzOncologyLow single digit$13.7$409.4
FilspariTravereNephropathy9%$12.2$135.6
EvomelaAcrotech/CASIOncology20%$8.7$44.8
TeriparatideAlvogenWomen's Health25%-40% 2$8.2$30.2
VaxneuvanceMerckInfectious DiseaseLow single digit$5.2$791.3
PneumosilSerum InstituteInfectious DiseaseLow single digit$3.8$161.5
NexteroneBaxterCardiovascularLow single digit$2.8$70.1
Ohtuvayre 3VeronaRespiratory Disease3%$2.7$41.6
CapvaxiveMerckInfectious DiseaseLow single digit$0.6$95.7
TzieldSanofiMetabolic DiseaseLess than 1%$0.2$58.0
19 Other Products$8.5
Total Royalty Receipts$119.6
Less: Amortization of Financial Royalty Assets4$10.8
GAAP Income from Royalty Assets$108.8

NOTES:

(1) Based on our agreement with Recordati, sales of Qarziba are undisclosed.

(2) We receive tiered profit sharing of 25% on quarterly profits less than $3.75 million, 35% on quarterly profits greater than $3.75 million but less than $7.5 million and 40% on quarterly profits greater than $7.5 million. If therapeutic equivalence is achieved, quarterly profit changes to 50% of quarterly profits.

(3) Ohtuvayre royalty receipts include an allocation of contractually earned milestones and royalties pertaining to financial royalty assets.

(4) Amounts represent the adjustments to the effective interest income recognized to total contractual payments recognized in the period.

Major Commercial-Stage Royalty Receipt Generating Assets

The following programs represent important revenue-generating components of our current portfolio. For information about the royalties owed to us for certain of these programs, see “Royalties” later in this business section.

Kyprolis (Amgen, Ono, BeiGene)

We supply Captisol to Amgen for use with Kyprolis (carfilzomib) and granted Amgen an exclusive product-specific license under our patent rights with respect to Captisol. Kyprolis is formulated with Ligand’s Captisol technology and is approved for the following:

In combination with dexamethasone, lenalidomide plus dexamethasone, daratumumab plus dexamethasone, or daratumumab and hyaluronidase-fihj and dexamethasone, or isatuximab and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

Our agreement with Amgen may be terminated by either party in the event of material breach or bankruptcy, or unilaterally by Amgen with prior written notice, subject to certain surviving obligations. Absent early termination, the agreement will terminate upon expiration of the obligation to pay royalties. Under this agreement, we are entitled to receive revenue from clinical and commercial Captisol material sales and a 1.5% to 3.0% royalty on annual net sales of Kyprolis. Amgen’s obligation to pay royalties does not expire until four years after the expiration of the last-to-expire patent covering Captisol. Our patents and applications relating to the Captisol component of Kyprolis are not expected to expire until 2033.

Qarziba (Recordati)

We receive royalties on Qarziba (dinutuximab beta) sales through our acquisition of Apeiron, announced in July 2024. Qarziba is a monoclonal antibody that is specifically directed against the carbohydrate moiety of disialoganglioside 2 (GD2), which is overexpressed on neuroblastoma cells. Dinutuximab beta was approved by the European Medicines Agency in 2017 for the treatment of high-risk neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with history of relapsed or refractory neuroblastoma, with or without residual disease.

Qarziba is commercially available in more than 35 countries. We receive a tiered mid-teen royalty on worldwide sales of Qarziba from Recordati and are entitled to receive over $25 million in potential milestone payments. See “Item 8. Financial Statements and Supplementary Data—Notes to Consolidated Financial Statements—Note (3), Acquisitions.”

Filspari (Travere, CSL Vifor, Renalys)

In early 2012, we licensed the world-wide rights to Filspari (sparsentan) to Travere Therapeutics. In September 2024, Travere received full approval from the FDA for Filspari, which was previously under accelerated approval, for the treatment of immunoglobulin A nephropathy (IgAN). Filspari is the first and only dual endothelin and angiotensin II receptor antagonist in development for rare kidney diseases and is the first non-immunosuppressive treatment indicated for IgAN. In February 2024, Travere and its partner CSL Vifor received approval for Filspari for the treatment of IgAN in Europe. Additionally, Travere has partnered with Renalys Pharma to develop and commercialize Filspari in Japan and other Asian countries. Renalys completed enrollment in its registrational Phase III clinical trial of sparsentan for IgAN in January 2025.

In February 2025, Travere announced completion of its Type C meeting with the FDA and plans to submit a supplemental New Drug Application (sNDA) seeking traditional approval of Filspari for focal segmental glomerulosclerosis (FSGS). The sNDA will be based on existing data from the Phase 3 DUPLEX and Phase 2 DUET studies of Filspari and is expected to be submitted around the end of the first quarter of 2025.

Under our license agreement with Travere, we are entitled to receive potential milestone payments, as well as a 9% royalty on worldwide sales.

Ohtuvayre (Verona, Nuance)

We acquired a royalty on Verona's Ohtuvayre (ensifentrine) through our acquisition of Vernalis in 2018 and acquired additional rights from Ohtuvayre inventors during the course of 2024 continuing through January 2025, bringing our royalty rate to 3% of global net sales. Ohtuvayre is a first-in-class selective dual inhibitor of the enzymes phosphodiesterase 3 and phosphodiesterase 4 (“PDE3 and PDE4”) that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule. Ohtuvayre is delivered directly to the lungs through a standard jet nebulizer without the need for high inspiratory flow rates or complex hand-breath coordination. Ohtuvayre was approved by the FDA in June 2024 for the maintenance treatment of chronic obstructive pulmonary disease ("COPD") in adult patients. Ohtuvayre is the first inhaled product with a novel mechanism of action available for the maintenance treatment of COPD in adult patients in more than 20 years. Verona sublicensed the right to develop and commercialize Ohtuvayre in Hong Kong, Macau, Taiwan, and mainland China to Nuance Pharma.

Verona is currently conducting Phase 2 trials for indication expansion in non-cystic fibrosis bronchiectasis, as well as a fixed-dose combination of ensifentrine + Long-Acting Muscarinic Antagonist (LAMA) for maintenance treatment of COPD. In

September 2024, Nuance Pharma (private), completed enrollment in its pivotal Phase 3 clinical trial evaluating Ohtuvayre for the maintenance treatment of COPD in China. Results from the trial are expected in 2025.

Rylaze (Jazz Pharmaceuticals)

In July 2021, Jazz announced the U.S. launch of Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn), previously referred to as JZP458. Rylaze, which was approved by the FDA in June 2021, is a recombinant erwinia asparaginase used as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase. In September 2023, Jazz announced that the European Commission (EC) had granted marketing authorization for Rylaze, to be marketed as Enrylaze. Jazz began a rolling launch in the second half of 2023.

We are eligible to receive tiered low-single digit royalties based on worldwide net sales of Rylaze, Enrylaze and any products resulting from this collaboration.

Vaxneuvance (Merck)

Vaxneuvance, a 15-valent pneumococcal conjugate vaccine, also known as V114, was approved in the U.S. in July of 2021 for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F in adults 18 years of age and older, and subsequently in children 6 weeks through 17 years of age in June of 2022. Vaxneuvance was also approved in Europe in October 2022 for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years and older and in infants, children and adolescents from 6 weeks to less than 18 years of age. Vaxneuvance utilizes CRM197 vaccine carrier protein, which is produced using the patent-protected Pelican Expression Technology platform, which we acquired in October 2020 through our acquisition of Pfenex. We are entitled to low single digit royalties derived from net sales of Vaxneuvance.

Capvaxive (Merck)

Capvaxive, a 21 valent pneumococcal vaccine, also known as V116, was approved by the FDA in June 2024 for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B in adults 18 years of age and older. Capvaxive is the first pneumococcal conjugate vaccine specifically designed for adults, and its 21 covered serotypes account for approximately 85% of cases of invasive pneumococcal disease among individuals 50 and over, including 8 serotypes not covered by any currently approved vaccines. Following the FDA approval, the US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (“ACIP”) voted to update the adult age-based pneumococcal vaccination guidelines to recommend Capvaxive for pneumococcal vaccination in adults 50 years of age and older. Additionally, ACIP issued a shared clinical decision-making recommendation for a supplemental dose of Capvaxive for adults 65 years of age and older who have completed their vaccine series with both PCV13 (pneumococcal 13-valent conjugate vaccine) and PPSV23 (pneumococcal 23-valent polysaccharide vaccine). Capvaxive utilizes CRM197 vaccine carrier protein, which is produced using the patent-protected Pelican Expression Technology platform, which we acquired in October 2020 through our acquisition of Pfenex. The FDA approval of Capvaxive triggered a $2 million milestone payment to Ligand, and we are entitled to a low single digit royalty on worldwide net sales.

Pneumosil (Serum Institute of India, SII)

SII began commercialization of its 10-valent pneumococcal conjugate vaccine, Pneumosil, which is produced using CRM197 made in the Pelican Expression Technology platform, in the second quarter of 2020. Pneumosil is designed primarily to help fight against pneumococcal pneumonia among children, with an advantage of targeting the most prevalent serotypes of the bacterium causing serious illness in developing countries. Pneumosil achieved WHO Prequalification in December 2019, allowing the product to be procured by United Nations agencies and Gavi, the Vaccine Alliance, and subsequently achieved Indian Marketing Authorization in July 2020, and SII announced commercial launch of the product in India in December 2020. We are entitled to a low-single digit royalty on net product sales of Pneumosil.

Teriparatide Injection Product (PF708) (Alvogen/Adalvo)

We acquired the teriparatide injection product with the acquisition of Pfenex in October 2020. Teriparatide injection is a drug indicated for various uses including the treatment of osteoporosis in certain patients at high risk for fracture. Teriparatide injection was developed using our Pelican Expression Technology and was approved by the FDA in 2019 in accordance with the 505(b)(2) regulatory pathway, with FORTEO as the reference product. Our commercialization partner, Alvogen, launched the product in June 2020 in the United States.

Alvogen has exclusively licensed the rights to commercialize and manufacture the teriparatide injection product in the U.S., while Adalvo has the rights to commercialize in the E.U. and other territories outside the U.S.. In accordance with our agreements with Alvogen, we are eligible to receive tiered gross profit sharing of between 25% and 40% of quarterly profits prior to an “A” therapeutic equivalence designation, which increases to a flat 50% if an “A” rating is achieved. In accordance with our agreements with Adalvo, we may be eligible to receive milestones and may also be eligible to receive up to 60% of gross profit derived from product sales and regional license fees, if approved, depending on geography, cost of goods sold and sublicense fees.

Evomela (Acrotech and CASI)

We supply Captisol to, and receive royalties from, Acrotech Biopharma for sales of Evomela in the United States, and CASI Pharmaceuticals for sales in China. Evomela is a Captisol-enabled melphalan IV formulation which is approved by the FDA for use in two indications:

a high-dose conditioning treatment prior to autologous stem cell transplantation (“ASCT”) in patients with multiple myeloma; and

for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.

Under the terms of the license agreement, Acrotech Biopharma has marketing rights worldwide excluding China, and CASI Pharmaceuticals has rights to market in China. We are eligible to a 20% royalty on global net sales of the Captisol-enabled melphalan product and revenue from Captisol material sales. Acrotech and CASI’s obligation to pay royalties will expire at the end of the life of the relevant patents or when a competing product is launched, whichever is earlier, but in no event less than ten years from commercial launch. Our patents and applications relating to the Captisol component of melphalan are not expected to expire until 2033. As described herein, we have entered into a settlement agreement with Teva and Acrotech Biopharma (the holder of the NDA for Evomela) which will allow Teva to market a generic version of Evomela in the United States in 2026, or earlier under certain circumstances. Absent early termination, the agreement will terminate upon expiration of the obligation to pay royalties. In December 2024, Acrotech issued a termination process letter to CASI alleging the Company materially breached the license agreement and failed to cure such breach, thus terminating the license agreement. CASI can continue to distribute Evomela in China for a reasonable wind down period not to exceed 24 months.

Nexterone (Baxter)

We have a license agreement with Baxter, related to Nexterone, a Captisol-enabled formulation of amiodarone, which is marketed in the United States and Canada. We supply Captisol to Baxter for use in accordance with the terms of a license agreement and a separate supply agreement between us and Baxter. Under the terms of the license agreement, we will continue to earn milestone payments, a low single digit royalty, and revenue from Captisol material sales. We will earn royalties on net sales of Nexterone through early 2033.

Tzield (Sanofi)

We acquired a royalty of less than 1% on net sales of Tzield through our acquisition of Tolerance Therapeutics (“Tolerance”) in the fourth quarter of 2023. Tzield is the first disease-modifying therapy to be approved in type 1 diabetes (“T1D”). It is a CD3-directed antibody indicated to delay the onset of Stage 3 T1D in adults and children aged 8 years and older with Stage 2 T1D. Tzield was granted Breakthrough Therapy Designation in 2019 and was approved by the FDA in November 2022. Tzield is marketed by Sanofi, following its acquisition of Provention Bio, Inc., the developer of Tzield, in 2023 for $2.9 billion. Sanofi also announced data from Tzield’s PROTECT Phase 3 trial, which showed Tzield’s potential to slow the progression of Stage 3 T1D in newly diagnosed children and adolescents. Tzield met the study’s primary endpoint, significantly slowing the decline of C-peptide levels, compared to placebo. Sanofi recently announced they have filed for Tzield's approval in Europe and China, expecting responses in the second half of 2025. Under our agreement with Tolerance, we are entitled to receive royalties through December 1, 2032.

Other Key Partnered Programs

We have a highly diversified partnered pipeline of assets that either have or are nearing regulatory approval that we consider particularly noteworthy given the area of research or value of the license terms. We are eligible to receive milestone payments and royalties on these programs. This list does not include all of our partnered programs. In the case of Captisol-related programs, we are also eligible to receive revenue for the sale of Captisol material supply. The following table represents development-stage assets with disclosed royalty rates:

Development stage assets with disclosed royalties
ProgramLicenseeRoyalty Rate
Bot/BalAgenus2.625%
UGN-301UroGen2.625 - 3.75%
CiforadenantCorvusMid-single digit to low-teen royalty
DGAT-1Viking3.0% - 7.0%
FBPase Inhibitor (VK0612)Viking7.5% - 9.5%
LasofoxifeneSermonix6.0% - 10.0%
MB07133Xi'an Xintong6%
Oral EPOViking4.5% - 8.5%
PradefovirXi'an Xintong9%
Qtorin rapamycinPalvella8.0% - 9.8%
SARM (VK5211)Viking7.25% - 9.25%
TR Beta (VK2809 and VK0214)Viking3.5% - 7.5%

Veklury (Gilead)

We supply Captisol to Gilead for sales of Veklury (remdesivir). Gilead received marketing approval from the FDA in October 2020. Veklury is an antiviral treatment for COVID-19. The product has regulatory approvals for the treatment of moderate or severe COVID-19 in over 70 countries. We are supplying Captisol to Gilead under a 10-year supply agreement. We are also supplying Captisol to Gilead’s voluntary licensing generic partners who are manufacturing remdesivir for 127 low- and middle-income countries. We receive our commercial compensation for this program through the sale of Captisol.

Botensilimab and Balstilimab (BOT/BAL) (Agenus)

In May 2024, we entered into the Agenus Agreement to support BOT/BAL clinical development, confirmatory Phase 3 trial, and launch readiness activities. Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (antibody) designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Over 900 patients have been treated with botensilimab in Phase 1 and Phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. Ligand is entitled to a 2.625% synthetic royalty on future global net sales generated by BOT/BAL pursuant to the Agenus Agreement. This rate may be adjusted depending on future events.

UGN-301

Additionally, under the terms of the Agenus Agreement, we are eligible for a tiered royalty of 2.625% to 3.75% on future net sales and 31.875% of the future milestone payments made by UroGen to Agenus related to UGN-301. The royalties and milestone payments owed to us could be adjusted up or down based upon predetermined future events and achievements of certain milestones. UGN-301 is an anti-CTLA-4 monoclonal antibody (zalifrelimab), prepared with reverse-thermal hydrogel for intravesical administration into the bladder. Intravesical administration of UGN-301 is designed to increase drug concentrations in the bladder without significant systemic exposure, potentially diminishing the systemic toxicity associated with CTLA-4 blockade. UroGen is evaluating UGN-301 as a monotherapy and as combination therapy for the intravesical treatment of high-grade non-muscle invasive bladder cancer.

TR-Beta - VK2809 and VK0214 (Viking)

Our partner, Viking, is developing VK2809, a novel selective thyroid hormone receptor beta (TR-beta) agonist with potential in multiple indications, including hypercholesterolemia, dyslipidemia and non-alcoholic steatohepatitis (NASH; also referred to as metabolic dysfunction associated steatohepatitis, MASH). Viking completed a Phase 2b clinical trial (the VOYAGE study) in patients with biopsy-confirmed NASH. At the 52-week mark, the drug reduced liver fat content by an average of 37% to 55% compared to baseline, with all treatment arms showing statistically significant improvements compared to placebo.

VK0214, another novel, orally available, TR-beta agonist, is in development for the potential treatment of X-linked adrenoleukodystrophy (“X-ALD”). VK0214 has been evaluated in a Phase 1b clinical trial in patients with the adrenomyeloneuropathy (“AMN”) form of X-ALD.

Under the terms of the agreement with Viking, we may be entitled to up to $375 million of development, regulatory and commercial milestones and a tiered royalty of 3.5% to 7.5% on potential future net sales of VK-2809 and VK-0214. Our TR-beta programs partnered with Viking are subject to CVR sharing, and a portion of the cash received will be paid out to CVR holders.

Ciforadenant – CPI-444 (Corvus)

Our partner, Corvus, is conducting a Phase 1b/2 clinical trial evaluating ciforadenant as a potential first line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The Phase 1b/2 study is being conducted by the Kidney Cancer Research Consortium (KCRC) and is led by The University of Texas MD Anderson Cancer Center. Under the terms of our agreement with Corvus, we are entitled to development and regulatory milestones and tiered royalties on potential future sales. Under the terms of our agreement with Corvus, we are entitled to milestones and tiered royalties ranging from mid-single digit to low-teens on potential future net sales.

Qtorin rapamycin (Palvella)

We acquired economic rights to Qtorin™ 3.9% rapamycin anhydrous gel (Qtorin rapamycin, formerly PTX-022) from Palvella in December 2018. Qtorin rapamycin is a novel, topical formulation of high-strength rapamycin currently in development for the treatment of Microcystic Lymphatic Malformations (“Microcystic LM”) and cutaneous venous malformations (“VMs”). The FDA has granted Breakthrough Therapy Designation, Fast Track Designation, and Orphan Designation to Qtorin rapamycin for the treatment of Microcystic LM. Microcystic LM is a chronically debilitating and lifelong genetic disease affecting an estimated more than 30,000 patients in the U.S. There are currently no FDA-approved treatments for Microcystic LM. Palvella is currently conducting a Phase 3 trial evaluating Qtorin rapamycin for the treatment of Microcystic LM and a Phase 2 trial evaluating Qtorin rapamycin for the treatment of cutaneous VMs. Under the terms of our agreement with Palvella, we are entitled to milestones and a tiered royalty of 8.0% to 9.8%.

Lasofoxifene (Sermonix)

Our partner, Sermonix has a license for the development of oral lasofoxifene, its lead investigational drug, for the United States and additional territories. Lasofoxifene is a selective estrogen receptor modulator in development for the treatment of breast cancer, discovered through the research collaboration between Pfizer and Ligand. Sermonix is currently conducting the Phase 3 ELAINE-3 clinical trial to assess the efficacy of lasofoxifene in combination with Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib (Verzenio®) compared to fulvestrant and abemaciclib in pre- and post-menopausal subjects with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation. In January 2024, Sermonix entered into a strategic collaboration and exclusive license agreement with Henlius for the rights to develop, manufacture and commercialize lasofoxifene in China. Henlius is currently conducting a Phase 3 ELAINE-3 multi-regional clinical trial in China.

Under the terms of our agreement with Sermonix, we are entitled to receive potential regulatory and commercial milestone payments, as well as a tiered royalty of 6% to 10% on potential future net sales.

Xinshumu (pradefovir) (Xi'an Xintong)

Xi'an Xintong received marketing approval from the Chinese National Medical Products Administration (NMPA) for Xinshumu (pradefovir mesylate tablets) in October 2024. Xinshumu is the first liver-targeted, novel Hepatitis B drug developed based on the HepDirect™ liver-targeting prodrug technology that utilizes a chemically modified prodrug of the active compound which is stable in blood and intestines and is activated by a liver specific CYP subtype enzyme to achieve high liver concentration of the active drug and low systemic exposure, reducing side effects in other organs for improved safety. Under the terms of our agreement with Xi'an Xintong, we are entitled to an annual licensing maintenance fee, milestones and a 9% royalty on potential future sales.

MB07133 (Xi'an Xintong)

Xi'an Xintong is also developing MB07133, a liver specific, HepDirect prodrug of cytarabine monophosphate, for the potential treatment of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. MB07133 is currently in Phase 2 in China. We are entitled to an annual licensing maintenance fee and a 6% royalty on potential future sales.

Full Portfolio Details

We have assembled one of the largest portfolios of biopharmaceutical assets in the industry which provides investors the opportunity to participate in the biotech industry while mitigating the industry’s usual inherent clinical binary risks. Our portfolio consists of assets which currently generate revenue through royalties on commercial products, as well as Captisol sales on commercial products. In addition to these assets, we have a substantial pipeline of development stage assets that currently generate contractual payments through milestone and license fees with future potential for royalties and Captisol material sales for those programs under our Captisol technology.

Approved
Partner NameProgramTherapeutic Area
Acrotech/CASIEvomelaOncology
Alvogen/AdalvoTeriparatideWomen's Health
Alvogen/Hikma/Nanjing King-FriendVoriconazoleInfectious Disease
Amgen/Beigene/OnoKyprolisOncology
BaxterNexteroneCardiovascular
EisaiFycompaCentral Nervous System
ElutiaECM portfolioMedical device/Cardiology
Exelixis/Daiichi-SankyoMinnebroCardiovascular
GileadVekluryInfectious Disease
IngenusTaxotereOncology
JazzRylazeOncology
MelintaBaxdelaInfectious Disease
MenariniFrovatriptanCentral Nervous System
FarevaNoxafil-IVInfectious Disease
MerckVaxneuvanceInfectious Disease
MerckCapvaxiveInfectious Disease
PelthosZELSUVMIInfectious Disease
NovartisMekinistOncology
Outlook TherapeuticsLytenavaOphthalmology
ParPosaconazoleInfectious Disease
PfizerDuaveeInflammatory/Metabolic
PfizerVfend-IVInfectious Disease
RecordatiQarzibaOncology
SageZulressoCentral Nervous System
SanofiTzieldMetabolic
Sedor/LupinSesquientCentral Nervous System
Serum Institute of IndiaPneumosilInfectious Disease
Serum Institute of IndiaMen5Infectious Disease
TravereFilspariMetabolic
VeronaOhtuvayreRespiratory Disease
Xi'an XintongPradefovirInfectious Disease
Phase 3/Pivotal or Regulatory Submission Stage
Partner NameProgramTherapeutic Area
AldeyraReproxalapOther/Undisclosed
BendaRxBendamustineOncology
MarinusGanaxalone IVCentral Nervous System
Ohara PharmaceuticalsJPH203Oncology
OptheaOPT-302Ophthalmology
Outlook TherapeuticsONS-5010Other/Undisclosed
PalvellaQtorin rapamycinOther/Undisclosed
SermonixLasofoxifeneOncology
SQ InnovationCE-FurosemideCardiovascular Disease
Sunshine LakeVilazodoneCentral Nervous System
Phase 2
Partner NameProgramTherapeutic Area
AgenusBot/BalOncology
AnebuloANEB-001Central Nervous System
CorvusCiforadenantOncology
CurXCE-TopiramateCentral Nervous System
Phoenix TissuePTR-01Genetic Disease
SatoSB206 (Japan)Infectious Disease
VeronaEnsifentrine (nebulizer)Non-Cystic Fibrosis Bronchiectasis
VeronaEnsifentrine + LAMA (Nebulizer)COPD
VikingVK5211Inflammatory/Metabolic
VikingVK2809Inflammatory/Metabolic
Xi'an XintongMB07133Oncology
Phase 1
Partner NameProgramTherapeutic Area
ArcellxACLX-001Oncology
ArcellxACLX-002Oncology
BelotecaCE-ZiprasidoneCentral Nervous System
China Resources Double CraneCX2101ACOVID 19
InvIOsAPN401Oncology
JazzJZP-341Long Acting Erwinia Asparaginase
Jupiter Biomedical ResearchVirightOncology
MerckV117Pneumococcal
NucorionNUC-1010Infectious Disease
UroGenUGN-301Oncology
VaxxasNanopatchInfectious Disease
VikingVK-0214Genetic Disease

Summary of selected programs available for license

In addition to ZELSUVMI, discussed above, we have a number of unpartnered programs focused on a wide-range of potential indications or diseases with the potential for further development or licensing:

ProgramDevelopment StageTargeted Indication or Disease
CE-IohexolPhase 2Diagnostics
Luminespib/Hsp90 InhibitorPhase 2Oncology
CE-Sertraline, Oral ConcentratePhase 1Depression
CCR1 AntagonistPreclinicalOncology
CE-BusulfanPreclinicalOncology
CE-Cetirizine InjectionPreclinicalAllergy
CE-Silymarin for Topical formulationPreclinicalSun damage
FLT3 Kinase InhibitorsPreclinicalOncology
GCSF Receptor AgonistPreclinicalBlood disorders

Manufacturing

We contract with a third-party manufacturer, Hovione, for Captisol production. Hovione operates FDA-inspected sites in the United States, Macau, Ireland and Portugal. Manufacturing operations for Captisol are performed primarily at Hovione's Portugal and Ireland facilities. We believe we maintain adequate inventory of Captisol to meet our current partner needs and that our Captisol capacity will be sufficient to meet future partner needs.

In the event of a Captisol supply interruption, we are permitted to designate and, with Hovione’s assistance, qualify one or more alternate suppliers. If the supply interruption continues beyond a designated period, we may terminate our agreement with Hovione. In addition, if Hovione cannot supply our requirements of Captisol due to an uncured force majeure event, we may also obtain Captisol from a third party and have previously identified such parties.

The original term of the agreement was through December 2024 and has been automatically renewed through December 2026. The agreement automatically renews for successive two-year renewal terms. Either party can give written notice of its intention to terminate the agreement no less than two years prior to the expiration of renewal term. In addition, either party may terminate the agreement for the uncured material breach or bankruptcy of the other party or an extended force majeure event. We may terminate the agreement for extended supply interruption, regulatory action related to Captisol or other specified events. We have ongoing minimum purchase commitments under our agreement with Hovione.

Competition

Some of the drugs we and our licensees and partners are developing may compete with existing therapies or other drugs in development by other companies. Furthermore, academic institutions, government agencies and other public and private organizations conducting research may seek patent protection with respect to potentially competing products or technologies and may establish collaborative arrangements with our competitors.

Our Captisol business may face competition from other suppliers of similar cyclodextrin excipients or other technologies that are aimed to increase solubility or stability of APIs.

Our competitive position also depends upon our ability to obtain patent protection or otherwise develop proprietary products or processes. For a discussion of the risks associated with competition, see below under“Item 1A. Risk Factors.”

Corporate and Governance Highlights

We are committed to policies and practices focused on environmental sustainability, positively impacting our social community and maintaining and cultivating good corporate governance. By focusing on such ESG policies and practices, we believe we can affect a meaningful and positive change in our community and maintain our open, collaborative corporate culture. We will continue our proactive shareholder and employee engagement in 2025. See www.ligand.com for information about our ESG policies and practices. However, note that the information contained on our website is not intended to be part of this filing.

Environmental, Health and Safety (“EHS”)

We are committed to providing a safe and healthy workplace, promoting environmental excellence in our communities, and complying with all relevant regulations and industry standards. We establish and monitor programs to reduce pollution, prevent injuries, and maintain compliance with applicable regulations. By focusing on such practices, we believe we can affect a meaningful, positive change in our community and maintain a healthy and safe environment. In early 2025, we completed our $2.6 million solar investment at Kansas University Innovation Park; made Environmental, Social and Governance (“ESG”) related charitable donations; and evolved numerous programs from our ESG-focused outreach committees. We expect to continue our effort and to refine our EHS policies and practices in 2025. More information on our EHS policies and initiatives is available on our website at www.ligand.com. However, note that the information contained on our website is not intended to be part of this filing.

Government Regulation

The research and development, manufacturing and marketing of pharmaceutical products are subject to regulation by numerous governmental authorities in the United States and other countries. We and our partners, depending on specific activities performed, are subject to these regulations. In the United States, pharmaceuticals are subject to regulation by both federal and various state authorities, including the FDA. In the U.S., the Federal Food, Drug and Cosmetic Act and the Public Health Service Act govern the research and development, testing, manufacture, quality, safety, efficacy, labeling, storage, record keeping, approval, advertising and promotion of pharmaceutical products. These activities are subject to additional regulations that apply at the state level. There are similar regulations in other countries as well. For both currently marketed products and products in development, failure to comply with applicable regulatory requirements at any time during the product development process, approval process or after approval, can, among other things, result in delays, the suspension of regulatory approvals, regulatory enforcement actions, as well as possible civil and criminal sanctions. In addition, changes in existing regulations could have a material adverse effect on us or our partners.

In particular, FDA approval is required before a drug or biological product may be marketed in the United States, and these products are also subject to other federal, state, and local statutes and regulations. The process required by the FDA before pharmaceutical products may be marketed in the United States generally involves the following:

completion of extensive preclinical laboratory tests and preclinical animal studies, certain of which must be performed in accordance with Good Laboratory Practice regulations and other applicable requirements;

submission to the FDA of an IND application, which must become effective before human clinical studies may begin;

approval by an independent institutional review board or ethics committee at each clinical site before each clinical study may be initiated;

performance of adequate and well-controlled human clinical studies in accordance with Good Clinical Practice (“GCP”) requirements to establish the safety and efficacy, or with respect to biologics, the safety, purity and potency of the product candidate for each proposed indication;

preparation of and submission to the FDA of an NDA or BLA after completion of all pivotal clinical studies that include substantial evidence of safety, purity, and potency of the drug from analytical studies and from results of nonclinical testing and clinical trials;

satisfactory completion of an FDA advisory committee review, where appropriate and if applicable;

a determination by the FDA within 60 days of its receipt of an NDA or BLA to file the application for review;

satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the proposed product is produced to assess compliance with cGMP, and potential FDA inspection of nonclinical study and clinical trial sites that generated the data in support of the NDA or BLA to ensure compliance with GCP; and

FDA review and approval of an NDA or BLA prior to any commercial marketing or sale of the drug in the United States.

Any products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. There also are continuing user fee requirements, under which the FDA assesses an annual program fee for each product identified in an approved NDA or BLA. Drug and biologic manufacturers and their subcontractors are required to register their establishments with the FDA and some state agencies, and are subject to periodic unannounced inspections by the FDA and some state agencies for compliance with cGMPs, which among other things, impose certain procedural and documentation requirements upon BLA or NDA holders and any third-party manufacturers. FDA regulations also require investigation and correction of any deviations from cGMPs and impose reporting requirements upon manufacturers and their subcontractors. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMPs and other aspects of regulatory compliance.

The FDA closely regulates the marketing, labeling, advertising and promotion of drug products and biologics. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences for non-compliance include, among other things:

restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market or product recalls;

fines, warning letters or holds on post-approval clinical studies;

refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals;

product seizure or detention, or refusal of the FDA to permit the import or export of products;

consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;

mandated modification of promotional materials and labeling and the issuance of corrective information;

the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or

injunctions or the imposition of civil or criminal penalties.

For a discussion of the risks associated with government regulations, see below under “Item 1A. Risk Factors.”

Patents and Proprietary Rights

We believe that patents and other proprietary rights are important to our business. Our policy is to file patent applications to protect technology, inventions and improvements to our inventions that are considered important to the development of our business. We also rely upon trade secrets, know-how, continuing technological innovations and licensing opportunities to develop and maintain our competitive position.

Patents are issued or pending for the following key products or product families. The scope and type of patent protection provided by each patent family is defined by the claims in the various patents. Patent terms may vary by jurisdiction and depend on a number of factors including potential patent term adjustments, patent term extensions, and terminal disclaimers. For each product or product family, the patents and/or applications referred to are in force in at least the United States, and for most products and product families, the patents and/or applications are also in force in European jurisdictions, Japan and other jurisdictions.

Captisol

Patents and pending patent applications covering Captisol and methods of making Captisol are owned by us. The patents covering the Captisol product with the latest expiration date is expected to be in 2033 (see, e.g., U.S. Patent No. 9,493,582 (expires Feb. 27, 2033)). Other patent applications covering methods of making Captisol, if issued, potentially have terms to 2041. We also own several patents and pending patent applications covering drug products containing Captisol as a component. Globally, we own over 400 issued patents covering all of the foregoing Captisol compositions, methods and related technology.

Ten Captisol patents in several families are listed in the Orange Book in connection with one or more prescription drugs currently on the market. These Captisol-enabled drugs include Nexterone (Baxter), Kyprolis (Amgen), Noxafil (Merck), Evomela (Acrotech/CASI), Baxdela (Melinta) and Zulresso (Sage). These patents are listed in the table below, and each patent family containing these patents has pending and/or granted counterparts in Europe, China and Japan.

Orange Book-listed Captisol Patents
CountryPatent No.TitleExpiration (nominal) ‡
United States7635773Sulfoalkyl Ether Cyclodextrin Compositions03/13/2029
United States8410077Sulfoalkyl Ether Cyclodextrin Compositions03/13/2029
United States9200088Sulfoalkyl Ether Cyclodextrin Compositions03/13/2029
United States10117951Sulfoalkyl Ether Cyclodextrin Compositions03/13/2029
United States9750822Sulfoalkyl Ether Cyclodextrin Compositions03/13/2029
United States9493582Alkylated Cyclodextrin Compositions And Processes For Preparing And Using The Same2/27/2033
United States10040872Alkylated Cyclodextrin Compositions And Processes For Preparing And Using The Same10/21/2033
United States10864183Injectable Nitrogen Mustard Compositions Comprising A Cyclodextrin Derivative And Methods Of Making And Using The Same5/28/2030
United States10940128Injectable Melphalan Compositions Comprising A Cyclodextrin Derivative And Methods Of Making And Using The Same5/28/2030
United States11020363Injectable Nitrogen Mustard Compositions Comprising A Cyclodextrin Derivative And Methods Of Making And Using The Same5/28/2030

‡ Expiration dates are calculated as 20 years from the earliest nonprovisional filing date to which priority is claimed, and do not take into account disclaimers or extensions that are or may be available in these jurisdictions.

Subject to compliance with the terms of the respective agreements, our rights to receive royalty payments under our licenses with our exclusive licensors typically extend for the life of the patents covering such developments. For a discussion of the risks associated with patent and proprietary rights, see below under“Item 1A. Risk Factors.”

Kyprolis

Patents protecting Kyprolis include those owned by Amgen and those owned by us. The United States patent listed in the Orange Book relating to Kyprolis owned by Amgen with the latest expiration date is not expected to expire until 2029. Patents and applications owned by Ligand relating to the Captisol component of Kyprolis are not expected to expire until 2033. Amgen filed suit against several generic drug companies over their applications to make generic versions of Kyprolis. Several generics have settled with Amgen on confidential terms. However, it has been publicly reported that the U.S. launch date for at least Breckenridge Pharmaceuticals’ generic product will be on a date that is held as confidential in 2027 or sooner, depending on certain occurrences. One generic company, Cipla Limited/Cipla USA, Inc. chose not to settle the litigation with Amgen, and proceeded to trial. The District Court upheld the validity of patent claims from three of the patents and the judgment was upheld on appeal.

Ligand UK Development Limited

Under the terms of our sale of Vernalis (R&D) Limited to HitGen in December 2020, Ligand retained a portfolio of fully-funded shots on goal, which now include S65487, a Bcl-2 inhibitor, and S64315, an Mcl-1 inhibitor for treatment of cancers, both of which are partnered with Servier in collaboration with Novartis. These programs and their IP are now owned by Ligand UK Development Limited, which has a worldwide patent portfolio of approximately 100 granted patents in over 40 countries. This patent portfolio is mature, with expected expiry dates up to 2033.

Pelican Expression Technology Platform

In connection with the merger of Pelican and Primrose, Pfenex assigned a global patent portfolio consisting of over 200 patents and over 25 pending patent applications to Pelican, while retaining four patents and five pending patent applications directed to methods of producing Erwinia asparaginase. Additionally, as part of the merger of Pelican and Primrose, Pfenex acquired a non-exclusive, worldwide, royalty-free, irrevocable, and fully sublicensable license to a portfolio of approximately 90 patents and approximately 15 pending patent applications which cover various aspects of the Pelican Expression Technology platform that are critical in helping support and retain contractual relationships including Jazz’s Rylaze, Merck’s Vaxneuvance and Capvaxive vaccines, Alvogen’s Teriparatide, and Serum Institute of India’s vaccine programs, including Pneumosil and MenFive vaccines, among others.

Novan

Through the Novan acquisition described above, we acquired a robust IP portfolio that consists of over 45 U.S. patents, 120 non-U.S. patents, and 25 pending patent applications worldwide along with substantial know-how and trade secrets. This IP portfolio provides material coverage for our platform technologies, licensed products and product candidates, in addition to ZELSUVMI, which was approved by the FDA on January 5, 2024. There are 14 issued U.S. patents covering ZELSUVMI which are listed in the Orange Book and which are expected to expire during the time period beginning in 2026 and ending in 2035. Upon the initial approval of ZELSUVMI, we applied for 1,280 days of patent term extension, or PTE, for the U.S. patent covering ZELSUVMI compositions. Assuming grant of the PTE application, the term of this patent may be extended from February 27, 2034, to August 30, 2037.

Apeiron

In connection with the acquisition of Apeiron in July 2024, we acquired a mature IP portfolio comprising of more than 300 patents worldwide. This IP portfolio supports a number of licensed products and product candidates, and comprises over 60 patents related to Qarziba with expected expiry dates between 2032 and 2034.

Human Capital Management

We recognize and take care of our employees by offering a wide range of competitive pay, recognition, and benefit programs. We are proud to provide our employees the opportunity to grow and advance as we invest in their education and career development. As of December 31, 2024, we have 68 full-time employees, of whom 24 are involved directly in scientific research and development activities.

We rely on skilled, experienced, and innovative employees to conduct the operations of the Company. Our key human capital objectives include identifying, recruiting, retaining, incentivizing and integrating our existing and new employees. We frequently benchmark our compensation practices and benefits programs against those of comparable industries and in the geographic areas where our facilities are located. We believe that our compensation and employee benefits are competitive and allow us to attract and retain skilled labor throughout our organization. Our notable health, welfare and retirement benefits include:

equity awards through our 2002 Stock Incentive Plan;

subsidized health insurance;

401(k) Plan with matching contributions;

tuition assistance program; and

paid time off.

We value diversity at all levels and continue to focus on extending our diversity and inclusion initiatives across our workforce. As of December 31, 2024, approximately 18% and 9% of our workforce are Asian and Hispanic, respectively. Additionally, 48% of our workforce is female and 52% is male. We believe that our business benefits from the different perspectives a diverse workforce brings.

We strive to maintain an inclusive environment free from discrimination of any kind, including sexual or other discriminatory harassment. Our employees have multiple avenues available through which inappropriate behavior can be reported, including a confidential hotline. All reports of inappropriate behavior are promptly investigated with appropriate action taken to stop such behavior.

Investor Information

Financial and other information about us is available on our website at www.ligand.com. We make available on our website, without charge, copies of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. You may obtain copies of these documents by visiting the SEC’s website at www.sec.gov. In addition, we use X (@Ligand_LGND) and our investor relations website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Investors should monitor our X account and our website, in addition to following our press releases, SEC filings, public conference calls and webcasts. These website addresses and the information accessible through our X account are not intended to function as hyperlinks, and the information contained in our website and in the SEC’s website is not intended to be a part of this filing.

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