About Ligand Pharmaceuticals
Ligand Pharmaceuticals Incorporated (Ligand), a biopharmaceutical company, focuses on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines.
The company employs research technologies, such as antibody discovery technologies, ion channel discovery technology, Pseudomonas fluorescens protein expression technology, formulation science and liver targeted pro-drug technologies to assist companies in their work toward securing prescription drug and biologic approvals. The company has partnerships and license agreements with over 140 pharmaceutical and biotechnology companies. Over 400 programs are in various stages of commercialization, development or research and are fully funded by the company’s collaboration partners and licensees. The company has contributed novel research and technologies for approved medicines that treat cancer, osteoporosis, fungal infections and postpartum depression, among others. The company’s collaboration partners and licensees have programs in clinical development targeting cancer, seizure, diabetes, cardiovascular disease, muscle wasting, liver disease, and kidney disease, among others. The company has over 1,600 issued patents worldwide.
The company has assembled its large portfolio of fully-funded programs either by licensing its own proprietary drug development programs, licensing its platform technologies, such as Captisol or OmniAb to partners for use with their proprietary programs, or acquiring existing partnered programs from other companies. For its internal programs, the company generally plans to advance drug candidates through early-stage drug development or clinical proof-of-concept and then seek partners to continue development and potential commercialization.
The company’s business model creates value for stockholders by providing a diversified portfolio of biotech and pharmaceutical product revenue streams. The company’s business model is based on doing what it does best: drug discovery, early-stage drug development, product reformulation and partnering. The company partners with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) to ultimately generate its revenue.
The company’s revenue consists of three primary elements: royalties from commercialized products, the sale of Captisol material, and contract revenue from license, milestone and other service payments. In addition to discovering and developing the company’s own proprietary drugs, it selectively pursues acquisitions to bring in new assets, pipelines, and technologies to aid in generating additional potential new revenue streams.
Partners and Licensees
The company has partnerships and license agreements with over 140 pharmaceutical and biotechnology companies.
Commercial and Clinical Stage Partnered Portfolio
The company has a large portfolio of potential revenue-generating programs, including over 400 fully-funded by its partners.
Selected Commercial Programs
The company has multiple programs under license with other companies that have products that are already being commercialized.
The company supplies Captisol to Amgen, Inc. (Amgen) for use with Kyprolis (carfilzomib), and granted Amgen an exclusive product-specific license under its patent rights with respect to Captisol. Kyprolis is formulated with Ligand’s Captisol technology and is approved in the United States for the following:
In combination with dexamethasone, lenalidomide plus dexamethasone, daratumumab plus dexamethasone, or daratumumab and hyaluronidase-fihj 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.
The company’s 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, the company is entitled to receive revenue from clinical and commercial Captisol material sales and royalties on annual net sales of Kyprolis.
The company supplies Captisol to Gilead Sciences, Inc. (Gilead) for the sale of Veklury (remdesivir). Gilead received marketing approval from the FDA in October 2020. Veklury is the first and only antiviral treatment of COVID-19 that is FDA approved. The product has regulatory approvals for the treatment of moderate or severe COVID-19 in over 50 countries and is included in more than 60 ongoing clinical trials. The company is supplying Captisol to Gilead under a recently signed 10-year supply agreement. The company is also supplying Captisol to Gilead’s voluntary licensing generic partners who are manufacturing remdesivir for 127 low- and middle-income countries. The company receives its commercial compensation for this program through the sale of Captisol.
Teriparatide Injection Product (PF708) (Alvogen/Adalvo/Kangchen)
The company acquired the Teriparatide Injection product with the acquisition of Pfenex Inc. (Pfenex) in October 2020. Teriparatide Injection is a drug indicated for uses, including the treatment of osteoporosis in certain patients at high risk for fracture. Teriparatide Injection was developed using the company’s 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. The company’s partner, Alvogen, launched the product in June 2020 in the United States.
Outside the United States, PF708 received marketing authorization throughout the European Union (EU) in August 2020 under the tradename Livogiva, was approved in Saudi Arabia in December 2020 under the name Bonteo and is in various stages of regulatory and marketing application processes around the globe, and upon approval, may be marketed as Teriparatide Injection or under various tradenames, such as Bonsity or Livogiva.
The company’s partner, Alvogen, has exclusively licensed the rights to commercialize and manufacture the teriparatide injection product in the United States, while their Adalvo business has the rights to commercialize in the EU, certain countries in the Middle East and North Africa (MENA), and the rest of world (ROW) territories (the latter defined as all countries outside of the EU, the U.S. and MENA, excluding Mainland China, Hong Kong, Singapore, Malaysia and Thailand). Kangchen has exclusively licensed to commercialize PF708, upon receipt of applicable marketing authorizations, in Mainland China, Hong Kong, Singapore, Malaysia and Thailand; and granted a non-exclusive right to conduct development activities in such countries with respect to PF708. Kangchen is responsible for all regulatory submissions, development costs and costs associated with regulatory approvals in these countries.
Evomela (Acrotech and CASI Pharmaceuticals, Inc. (CASI))
The company supplies Captisol to Acrotech Biopharma for sales of Evomela in the U.S. and to CASI for the sale of Evomela in China. Evomela received market approval by the China National Medical Products Administration (NMPA). It is the only approved and commercially available melphalan product in China. Evomela is a Captisol-enabled melphalan Intravenous (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.
Evomela has been granted Orphan Designation by the FDA for use as a high-dose conditioning regimen for patients with multiple myeloma undergoing ASCT. The Evomela formulation avoids the use of propylene glycol, which has been reported to cause renal and cardiac side-effects that limit the ability to deliver higher quantities of therapeutic compounds. The use of the Captisol technology to reformulate melphalan is anticipated to allow for longer administration durations and slower infusion rates, potentially enabling clinicians to safely achieve a higher dose intensity of pre-transplant chemotherapy.
Under the terms of the license agreement, Acrotech Biopharma (Acrotech Biopharma L.L.C.) has marketing rights worldwide excluding China and CASI has rights to market in China. The company’s patents and applications relating to the Captisol component of melphalan are not expected to expire until 2033. The company has a settlement agreement with Teva (Teva Pharmaceuticals USA, Inc.; Teva Pharmaceutical Industries Ltd.; and Actavis, LLC) 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 on June 1, 2026, or earlier under certain circumstances.
On July 16, 2021, Merck & Co., Inc. (Merck) announced FDA approval of Vaxneuvance, a 15-valent pneumococcal conjugate vaccine, also known as V114, 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. VAXNEUVANCE is a 15-valent pneumococcal vaccine utilizing CRM197 vaccine carrier protein, which is produced using the patent-protected Pelican Expression Technology platform. V114 previously received Breakthrough Therapy Designation from the FDA for the prevention of invasive pneumococcal disease in pediatric patients 6 weeks to 18 years of age and adults 18 years of age and older. Pneumococcal disease in adults is on the rise in many countries, and V114 consists of pneumococcal polysaccharides from 15 serotypes conjugated to CRM197 carrier protein, including serotypes 22F and 33F, which are commonly associated with invasive pneumococcal disease in older adults. On October 20, 2021, Merck announced that the CDC Advisory Committee on Immunization Practices (ACIP) unanimously voted in the favor of updates to the pneumococcal vaccination recommendations for adults 65 years and older, and for adults ages 19 to 64 with certain underlying medical conditions or other disease risk factors. In both groups the ACIP voted to provisionally recommend vaccination with either a sequential regimen of Vaxneuvance and Pneumovax_23 or a single dose of 20-valent pneumococcal conjugate vaccine. On January 28, 2022, final recommendations were published in the CDC’s Morbidity and Mortality Weekly Report (MMWR). On December 1, 2021, Merck announced the FDA accepted for priority review a sBLA (supplemental Biologics License Application) for Vaxneuvance for the prevention of invasive pneumococcal disease in children 6 weeks through 17 years of age, with a PDUFA date of April 1, 2022.
On December 15, 2021, Merck announced the European Commission approval of Vaxneuvance for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years and older. The approval allows marketing of VAXNEUVANCE in all 27 EU Member States plus Iceland, Norway, and Lichtenstein. The company is entitled to low single digit royalties derived from net sales, depending on the territory.
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 the 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.
Rylaze (JZP-458) (Jazz)
In July 2021, Jazz Pharmaceuticals, Inc. (Jazz) announced the 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) or lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase. Additionally, Jazz is utilizing the company’s technology for the development of PF745 (JZP341), a long-acting Erwinia asparaginase for the treatment of acute lymphoblastic leukemia and other hematological malignancies. Jazz has worldwide rights to develop and commercialize PF745.
The company has a license agreement with Baxter International, Inc. (Baxter), related to Baxter's Nexterone, a Captisol-enabled formulation of amiodarone, which is marketed in the United States of America and its territories and possessions (including Puerto Rico) (United States or U.S.) and Canada. The company supplies Captisol to Baxter for use in accordance with the terms of the license agreement under a separate supply agreement. Under the terms of the license agreement, the company will continue to earn milestone payments, royalties, and revenue from Captisol material sales. The company is entitled to earn royalties on the sale of Nexterone through early 2033.
The company has a license agreement with Sage Therapeutics, Inc. (SAGE), related to SAGE's Zulresso, a Captisol-enabled formulation of brexanolone for the treatment of postpartum depression (PPD). Under the terms of the agreement, the company receives royalties and revenue from Captisol material sales.
The company has a supply agreement with Merck related to Merck’s NOXAFIL-IV, a Captisol-enabled formulation of posaconazole for IV use. NOXAFIL-IV is marketed in the United States, EU and Canada. The company receives its commercial compensation for this program through the sale of Captisol.
Duavee or Duavive (bazedoxifene/conjugated estrogens) and Viviant/Conbriza (Pfizer)
Pfizer, Inc. (Pfizer) is marketing bazedoxifene, a selective estrogen receptor modulator, under the brand names Viviant and Conbriza in various territories for the treatment of postmenopausal osteoporosis. Pfizer is responsible for the marketing of bazedoxifene, a synthetic drug specifically designed to reduce the risk of osteoporotic fractures while also protecting uterine tissue. Pfizer has combined bazedoxifene with the active ingredient in Premarin to create a combination therapy for the treatment of post-menopausal symptoms in women. Pfizer is marketing the combination treatment under the brand names Duavee and Duavive in various territories. Net royalties on annual net sales of Viviant/Conbriza and Duavee/Duavive are each payable to the company through the life of the relevant patents or ten years from the first commercial sale, whichever is longer, on a country by country basis.
Aziyo Portfolio (Aziyo)
The company receives a share of revenue from the marketed Aziyo portfolio of commercial pericardial repair and CanGaroo Envelope Extracellular matrix (ECM) products. In addition, the company has the potential to receive a share of revenue and potential milestones from the marketed CanGaroo ECM Envelope for cardiac implantable electronic devices. Aziyo’s products are medical devices that are designed to permit the development and regrowth of human tissue.
Exemptia, Vivitra, Zybev and Bryxta (Zydus Cadila)
Zydus Cadila’s Exemptia (adalimumab biosimilar) is marketed in India for autoimmune diseases. Zydus Cadila uses the Selexis, SA (Selexis) technology platform for Exemptia. The company is entitled to earn royalties on sales by Zydus Cadila Healthcare, Ltd (Zydus Cadila) for ten years following the first commercial sale.
Zydus Cadila’s Vivitra (trastuzumab biosimilar) is marketed in India for breast cancer. Zydus Cadila uses the Selexis technology platform for Vivitra. The company is entitled to earn royalties on sales by Zydus Cadila for ten years following the first commercial sale.
Zydus Cadila’s Bryxta and Zybev (bevacizumab biosimilar) is marketed in India for various indications. Zydus Cadila uses the Selexis technology platform for Bryxta and Zybev. The company is entitled to earn royalties on sales by Zydus Cadila for ten years following the first commercial sale.
Minnebro is marketed in Japan for the treatment of hypertension. The company’s partner, Exelixis, Inc. (Exelixis), entered into a collaboration agreement with Daiichi Sankyo Company, Ltd. (Daiichi Sankyo) for the development of esaxerenone, a mineralocorticoid receptor antagonist. Under the terms of the agreement with Exelixis, the company is entitled to receive a royalty on future sales.
Summary of Selected Development Stage Programs
The company has multiple fully-funded partnered programs that are either in or nearing the regulatory approval process, or given the area of research or value of the license terms, it considers particularly noteworthy. The company is eligible to receive milestone payments and royalties on these programs.
Sparsentan (Travere Inc. (Travere))
The company’s partner, Travere, is developing sparsentan for orphan indications of severe kidney diseases and is running an on-going global pivotal Phase 3 clinical trial (DUPLEX) for sparsentan for the treatment of Focal segmental glomerulosclerosis (FSGS). Additionally, Travere is running a global pivotal Phase 3 clinical trial (PROTECT) evaluating the long-term nephroprotective potential of sparsentan for the treatment of IgAN nephropathy, a rare, immune complex mediated chronic glomerular disease. Certain patient groups with severely compromised renal function, including those with FSGS and IgAN, exhibit extreme proteinuria resulting in progression to dialysis and a high mortality rate. Sparsentan, with its unique dual blockade of angiotensin and endothelin receptors, is expected to provide meaningful clinical benefits in mitigating proteinuria in indications where there are no approved therapies.
In February of 2021, Travere announced that sparsentan achieved its pre-specified interim FSGS partial remission of proteinuria endpoint (FPRE) in the DUPLEX Phase 3 study after 36 weeks of treatment. Sparsentan demonstrated a statistically significant response on FPRE compared to the active control, irbesartan (p=0.0094). Preliminary results from the interim analysis suggest that sparsentan has been generally well-tolerated and has shown a comparable safety profile to irbesartan. Travere plans to submit an NDA seeking accelerated approval of sparsentan for FSGS in the United States in mid-2022 after obtaining additional estimated glomerular filtration rate (eGFR) data from the DUPLEX Study.
In August of 2021, Travere announced positive topline interim results from the ongoing Phase 3 PROTECT study of sparsentan in IgAN. Sparsentan treatment demonstrated a statistically significant mean reduction of proteinuria from baseline after 36 weeks, more than threefold the reduction of active comparator irbesartan (p<0.0001). In the first quarter of 2022, Travere expects to submit an NDA seeking accelerated approval of sparsentan for IgAN in the United States.
Additionally, Travere and Vifor Pharma entered into a licensing agreement in September of 2021 for the commercialization of sparsentan in Europe, Australia and New Zealand. Traver and Vifor Pharma expect to submit a combined IgAN and FSGS Marketing Authorisation Application (MAA) in mid-2022 for conditional marketing authorization of sparsentan in Europe.
TR-Beta - VK2809 and VK0214 (Viking Therapeutics, Inc. (Viking))
The company’s 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). VK2809 is in a Phase 2b clinical trial (the VOYAGE study) in patients with biopsy-confirmed NASH. Viking has previously announced positive results from a Phase 2a trial of VK2809 in hypercholesterolemia and fatty liver disease. VK0214 is in Phase 1 clinical development, and had been granted orphan drug study by the U.S. Food and Drug Administration (FDA) for the treatment of X-linked adrenoleukodystrophy (X-ALD). The company’s TR Beta programs partnered with Viking are subject to contingent value right (CVR) sharing and a portion of the cash received will be paid out to CVR holders.
Batoclimab (HanAll Biopharma Co., Ltd. (HanAll), Immunovant, and Harbour)
The company’s partner, HanAll has granted Immunovant Sciences GmbH (Immunovant) an exclusive license for the development, manufacture and marketing of Batoclimab for the treatment of pathogenic IgG-mediated autoimmune diseases in the U.S., Canada, Mexico, the EU, the United Kingdom, Switzerland, Latin America, the Middle East and North Africa. Immunovant announced the initiation of a Phase 3 trial in H2 in myasthenia gravis (MG) in the first half of 2022 and another one in another inflammatory disease while expanding into two new indications to be announced by Q3. Additionally, HanAll and Harbour are collaborating to develop Batoclimab for similar treatment in China and Korea. Harbour BioMed Shanghai Co., Ltd. (Harbour) is conducting three registrational Phase 2/3 trials in China in MG, thyroid eye disease and Primary Immune Thrombocytopenia. HanAll retains the rights to Batoclimab in Korea and Harbour will control the marketing in China. As part of its agreement with HanAll, the company is entitled to development and regulatory milestones and royalties on potential future sales from HanAll and sublicense revenues from Immunovant and Harbour based on amounts received by HanAll.
CRM197 is a non-toxic mutant of diphtheria toxin. It is a well characterized protein and functions as a carrier for polysaccharides and haptens, making them immunogenic. CRM197 is used in prophylactic and therapeutic vaccine candidates. The company has developed CRM197 production strains using its Protein Expression Technology platform and supply preclinical grade and current good manufacturing practice (cGMP) CRM197 (PeliCRM) to several vaccine development focused pharmaceutical customers.
The company’s partners Merck and SII have exclusively licensed unique production strains for use in their conjugate vaccine products and candidates for pneumococcal and meningitis bacterial infections. Pneumococcus bacterium (Streptococcus pneumoniae) is a leading cause of severe pneumonia and major cause of morbidity and mortality worldwide. CRM-197 made in the Pelican Expression Technology platform is also used by Merck in its investigational vaccine candidates, including the V116. Additionally, in 2021 SII completed a Phase 3 study of a pentavalent meningococcal conjugate vaccine candidate (NmCV-5) that utilizes CRM197 made in the Pelican Expression Technology platform. NmCV-5 prequalification by WHO is projected as early as the third quarter of 2022.
Ensifentrine – RPL554 (Verona Pharma plc (Verona))
The company’s partner, Verona, is conducting a comprehensive Phase 3 clinical trial to evaluate the efficacy and safety of nebulized ensifentrine in patients with moderate to severe Chronic obstructive pulmonary disease (COPD) with top-line results expected in 2022.
The company’s partner, Janssen, is developing Teclistamab, an off-the-shelf T-cell redirecting , bispecific antibody targeting BCMAxCD3 that was discovered in part with the OmniAb platform technology. Janssen announced that it submitted a Biologics license application (BLA) on December 29, 2021, for the treatment of patients with relapsed or refractory multiple myeloma. The application was supported by the data from the MajesTEC-1 Phase 2 trial that showed continued deep and durable responses. Teclistamab is also conducting several Phase 1 trials in multiple myeloma, as a single agent and in combination with daratumumab or talquetamab or Tecentriq.
Janssen is also developing JNJ-67371244, an anti-CD33xCD3 antibody discovered in part with the OmniAb platform technology. Janssen is conducting a Phase I trial for cancer therapy. The company is entitled to earn development and regulatory milestones based on the development of JNJ-67371244.
Janssen is also developing JNJ-70218902, a T-cell redirecting agent antibody discovered in part with the OmniAb platform technology. Janssen is conducting a Phase I trial for cancer therapy for patients with metastatic castration resistant prostate cancer. The company is entitled to earn development and regulatory milestones based on the development of JNJ-70218902.
Janssen is also developing JNJ-78306358, a T-cell redirecting bispecific antibody targeting HLA-G, discovered in part with the OmniAb platform technology. Janssen is conducting a Phase 1 trial in patients with advanced solid tumors. The company is entitled to earn development and regulatory milestones based on the development of JNJ-78306358.
M6223 (Merck KGaA)
The company’s partner, Merck KGaA, is conducting a Phase 1 trial of M6223, an anti-TIGIT antibody discovered with the OmniAb platform, in patients with metastatic or locally advanced solid unresectable tumors in combination with bintrafusp alfa. Under the terms of the agreement, the company is entitled to sublicense revenues, milestones and royalties on potential future net sales.
SARM - VK5211 (Viking)
Viking is also developing VK5211, a novel, potentially best-in-class Selective Androgen Receptor Modulator (SARM) for patients recovering from hip-fracture. SARMs retain the beneficial properties of androgens without undesired side-effects of steroids or other less selective androgens. In a Phase 2 clinical trial, VK5211 demonstrated statistically significant, dose dependent increases in lean body mass.
Ganaxalone IV (Marinus)
The company’s partner, Marinus Pharmaceuticals, Inc. (Marinus), is conducting Phase 3 clinical trials with Captisol-enabled ganaxolone IV in patients with refractory status epilepticus. Marinus has exclusive worldwide rights to Captisol-enabled ganaxolone, a GABAA receptor modulator, for use in humans. The company is entitled to development and regulatory milestones, revenue from Captisol material sales, and royalties on potential future sales.
The company’s partner, Aptevo Therapeutics (Aptevo), is conducting a Phase 1 trial of APVO436, a bispecific anti-CD123xCD3 for the treatment of acute myeloid leukemia and high-grade myelodysplastic syndrome. There is a high unmet medical need for targeted immunotherapies, such as APVO436 that can potentially treat patients with relapsed or refractory disease, or patients who cannot tolerate traditional chemotherapy. Under the terms of the agreement with Aptevo, the company is entitled to development and regulatory milestones and royalties on potential future net sales.
The company’s partner, Genmab, in collaboration with BioNTech is conducting two Phase 2 trials of GEN1046, a bispecific targeting PD-L1 and 4-1BB, as monotherapy or in combination for use in patients with relapsed/refractory metastatic non-small cell lung cancer (NSCLC) or malignant solid tumors. Under the terms of the agreement with Genmab, the company is entitled to clinical and regulatory milestones and royalties on potential future sales.
Genmab is also developing GEN1047, an anti-B7H4xCD3 bispecific antibody, in part isolated from OmniAb platform technology. Genmab is conducting a Phase 1/2 trial in solid tumors. Under the terms of the agreement with Genmab, the company is entitled to clinical and regulatory milestones and royalties on potential future sales.
Sym022 and Sym023 (Symphogen/Servier)
The company’s partner, Symphogen (acquired by Servier), is conducting Phase 1 trials of SYM022 and SYM023 to determine if they are safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy for which no standard therapy is available. Under the terms of the agreement with Symphogen, the company is entitled to sublicense revenues, milestones and royalties on potential future net sales.
Symphogen/Servier is also developing an anti-CD73 antibody, developed with OmniAb platform technology, in Phase I trial to assess the safety and tolerability in patients with solid tumors as a monotherapy or in combination with Sym021 (anti-PD-1). Under the terms of the agreement with Symphogen, the company is entitled to sublicense revenues, milestones and royalties on potential future net sales.
Symphogen/Servier is also developing an anti-NKG2A antibody, developed with OmniAb platform technology, in Phase 1a/1b trial to assess the safety, tolerability and preliminary anti-neoplastic activity in patients with solid tumors as a monotherapy or in combination with Sym021 (anti-PD-1) or anti-HER2 or anti-EGFR. Under the terms of the agreement with Symphogen, the company is entitled to sublicense revenues, milestones and royalties on potential future net sales.
Pursuant to the WuXi Agreement (The Platform License Agreement, dated March 23, 2015, by and between Ligand and WuXi, as amended), the company has granted WuXi Biologics Ireland Limited (WuXi) a non-exclusive license to use its OmniRat, OmniMouse and OmniFlic platforms solely to research, develop and make antibodies, and it has agreed to use commercially reasonable efforts to deliver to WuXi animals from such platforms to support WuXi’s licensing rights under the WuXi Agreement. Further, WuXi has the right to out-license antibodies it discovers (whether for itself or at the direction of out-licensees) under the WuXi Agreement to out-licensees worldwide. The company is entitled to royalties in the low single digits on net sales of products.
In addition to other earlier stage programs, the following programs have been licensed pursuant to the WuXi Agreement:
Zimberelimab AB122/GLS010 (Arcus Biosciences, Inc. (Arcus) and Gloria)
The company’s partner, WuXi, has outlicensed the rights to certain programs using the OmniAb technology to Arcus and Gloria. Arcus is conducting multiple Phase 1 and Phase 2 trials to evaluate the safety and tolerability and efficacy of Zimberelimab in subjects with advanced solid tumors as monotherapy or in combination with Etrumadenant, domvanalimab. Additionally, Gloria, has announced approval in China for zimberelimab for the treatment of recurrent or refractory classical Hodgkin’s lymphoma. Gloria is also conducting a Phase 2 of zimberelimab monotherapy in patients with recurrent or metastatic cervical cancer. Under the terms of the company’s agreement with WuXi, the company is entitled to royalties on potential future sales.
Sugemalimab CS1001 (CStone)
WuXi has also outlicensed the rights to certain programs using the OmniAb technology to CStone. CStone announced approval in China for Sugemalimab (brand name Cejemly) for first-line treatment of metastatic NSCLC. Pfizer is responsible for the commercialization in China via a 2020 strategic collaboration with CStone while EQRx has licensed exclusive rights to sugemalimab for the development and commercialization outside of China. CStone Pharmaceuticals (Suzhou) Co., Ltd. (CStone) is conducting multiple Phase 2 and Phase 3 trials to evaluate the efficacy and safety of Sugemalimab to treat patients with natural killer cell/T-cell lymphoma and classical Hodgkin’s lymphoma, second line treatment in NSCLC, and gastric or esophageal cancers. Under the terms of the company’s agreement with WuXi, it is entitled to royalties on potential future sales.
Ciforadenant – CPI-444 (Corvus)
The company’s partner, Corvus Pharmaceuticals, Inc. (Corvus), is conducting a Phase 1b/2 clinical trial in patients with renal cell carcinoma and metastatic castration resistant prostate cancer to evaluate Ciforadenant, an antagonist of adenosine A2A, in combination with the immunotherapy drug atezolizumab. Positive preliminary data was presented in February at American Society of Clinical Oncology (ASCO) 2020 Genitourinary Cancers Symposium (ASCO-GU) and additional data was presented at ASCO 2020 in May/June. Ciforadenant is also being evaluated in a Phase 1b/2 trial in combination with atezolizumab in patients with non-small cell lung cancer who have failed no more than two prior regimens. Under the terms of its agreement with Corvus, the company is entitled to development and regulatory milestones and tiered royalties on potential future sales.
FYCOMPA IV (Eisai)
The company’s partner, Eisai Inc. (Eisai), completed an open-label, single group assignment, multicenter, Phase 2 study in Japan to evaluate the safety and tolerability of intravenous perampanel, formulated with Captisol, as substitute for oral tablets as an adjunctive therapy in patients with partial onset seizures (including secondarily generalized seizures) or primary generalized tonic-clonic seizures. The company is entitled to revenue from Captisol material sales and tiered royalties on potential future sales.
Pevonedistat - TAK-924 (Millennium/Takeda Pharmaceuticals Company Limited (Takeda))
The company’s partner, Millennium Pharmaceuticals, Inc. ((Millennium)/Takeda), is conducting Phase 3 trials for the development of pevonedistat for the treatment of acute myeloid leukemia. Pevonedistat is a Captisol-enabled Nedd8-Activating Enzyme Inhibitor.
The company acquired certain economic rights to SB206 (KINSOLUS) from Novan, Inc. (Novan) in May 2019. SB206 is a topical nitric-oxide antiviral gel for the treatment of viral skin infections, including molluscum contagiosum (MC). MC is an infection, which causes skin lesions that affect approximately 6 million people in the United States annually, with the greatest incidence in children aged one to 14 years. In June of 2021, Novan reported positive topline efficacy and favorable safety data at Week 12 from the B-SIMPLE4 pivotal Phase 3 clinical study of SB206 for the treatment of MC, with primary endpoint achieving statistical significance (p-value < 0.0001) and no serious adverse events related to treatment with SB206. Novan intends to submit a New Drug Application (NDA) to the FDA for the treatment of MC in the fourth quarter of 2022.
PTX - 022 (Palvella)
The company acquired the economic rights to PTX-022 from Palvella Therapeutics, Inc. (Palvella) in December 2018. PTX-022 is a novel, topical formulation comprising high-strength rapamycin in development to treat pachyonychia congenita (PC). PC is a serious, chronically debilitating lifelong monogenic rare skin disease with no approved treatment. Palvella is conducting the Phase 3 VAPAUS study to evaluate the safety and efficacy of PTX-022 (QTORIN 3.9% rapamycin anhydrous gel) in the treatment of adults with PC.
Lasofoxifene is a selective estrogen receptor modulator for osteoporosis treatment and other diseases, discovered through the research collaboration between Pfizer and the company. Its partner, Sermonix Pharmaceuticals, LLC (Sermonix) has a license for the development of oral lasofoxifene for the United States and additional territories. Sermonix is the Phase 2 ELAINE 1 trial assessing oral lasofoxifene versus intramuscular fulvestrant for the treatment of ER+/HER2- breast cancer in patients with an ESR1 mutation. Lasofoxifene is also being studied in ELAINE 2 trial in combination with Eli Lilly and Company's (Eli Lilly) CDK4 and 6 inhibitor, Verzenio (abemaciclib). Topline data are expected for both ELAINE trials in the first half of 2022.
Pradefovir (Xi'an Xintong Medicine Research (Xi'an Xintong))
The company’s Chinese licensee, Xi'an Xintong Medicine Research (following its acquisition of Chiva Pharmaceuticals), is developing pradefovir, an oral liver-targeting prodrug of the HBV DNA polymerase/reverse transcriptase inhibitor adefovir, for the potential treatment of Hepatitis B Virus (HBV) infection. Pradefovir was developed using Ligand’s HepDirect technology. In September 2019, Xi'an Xintong Medicine Research reported positive results from a Phase 2 trial of pradefovir, showing good efficacy, safety and tolerability. At the dose of 75 mg, the reduction of DNA viral load, the percentage of no viral load detected, and HBeAg negative conversion rate were better than tenofovir disoproxil fumarate (TDF) after 24 weeks of treatment. Overall incidence of side effects was less than TDF and there was no renal or skeletal toxicity. Xi'an Xintong Medicine Research is conducting a Phase 3 trial. The company is entitled to an annual licensing maintenance fee and royalties on potential future sales.
MB07133 (Xi'an Xintong)
Chinese licensee Xi'an Xintong Medicine Research is also developing MB07133, a liver specific, HepDirect prodrug of cytarabine monophosphate, for the potential treatment of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. MB07133 is in Phase 1 in China. The company is entitled to an annual licensing maintenance fee and royalties on potential future sales.
Summary of Selected Collaborations
In December 2020, the company entered into a license and collaboration agreement with GSK to leverage its unique expertise in small molecule therapeutics targeting transmembrane proteins. The company is responsible for the majority of preclinical activities up to lead optimization with both Ligand and GlaxoSmithKline (GSK) collaborating to identify candidates for IND-enabling studies. GSK has the exclusive option to license any identified inhibitors and will be responsible for further development and commercialization of any drug candidates identified through the collaboration. In December 2021, the company entered into a second collaborative drug discovery program for a new genetically validated molecular target.
In December 2018, the company entered into a license and collaboration agreement with Roche to develop and commercialize small molecule ion channel modulators for the treatment of neurological disorders and in May 2020 amended the license and collaboration agreement to include a second target. These programs incorporate the company’s technology platform for ion channel drug discovery and are directed at specific ion channel targets expressed in neurons. For all programs the company will be responsible for most preclinical activities up to lead optimization with both the company and Roche applying resources to identify candidates for entry into late stage preclinical and Investigational New Drug (IND) enabling studies. Thereafter, Roche will be responsible for the further development and commercialization of the programs.
Cystic Fibrosis Foundation Collaboration
In May 2018, the company announced an award of up to $11 million from the Cystic Fibrosis Foundation for a project focused on the discovery of therapeutics to treat patients with cystic fibrosis (CF) caused by nonsense mutations. Nonsense mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene result in the premature termination of protein synthesis and the formation of truncated, non-functional CFTR.
The company has multiple programs under license with other companies that have products that are already being commercialized.
Summary of Selected Internal Development Programs
The company has a number of internal development or unpartnered programs focused on a wide-range of potential indications or disease.
The Captisol-enabled (CE)-Iohexol program was established in January 2018 to develop a next-generation contrast agent for diagnostic imaging with a reduced risk of renal toxicity. Contrast-induced acute kidney injury (CI-AKI) is the acute impairment of renal function following intravascular administration of an iodinated contrast agent, and occurs most frequently following coronary angiography, percutaneous coronary intervention and contrast-enhanced computed tomography, especially among patients at risk of renal injury, such as those with advanced age, diabetes or heart failure.
In July 2019, the company announced positive top-line results from a Phase 1 clinical trial CE-Iohexol conducted in Canada. The trial achieved the primary endpoint by demonstrating pharmacokinetic bioequivalence of CE-Iohexol injection and a reference Iohexol injection (OMNIPAQUE) after IV administration in healthy adults. The company submitted an IND with the FDA in November and received a Study May Proceed letter in December 2020 along with feedback from the FDA on the clinical plan.
The Luminespib/Hsp90 Inhibitor is a Phase 2-ready Hsp90 inhibitor, previously investigated in clinical trials for cancer. Third-party academic drug analyses suggest a potential role for heat shock protein 90 (Hsp90) inhibitors in treating novel coronavirus (COVID-19) infection. Based on these studies, the company is evaluating potential collaborations or partnerships relating to intravenous luminespib (AUY-922) as a potential treatment for patients with COVID-19.
The company contracts with a third party manufacturer, Hovione FarmCiencia, S.A. (Hovione), for Captisol production. Hovione operates FDA-inspected sites in the United States, Macau, Ireland and Portugal. Manufacturing and distribution operations for Captisol are performed primarily at Hovione's Portugal and Ireland facilities.
The company’s OmniAb antibody technology faces competition from suppliers of other transgenic animal systems that are also available for antibody drug discovery, such as AbCellera Biologics.
Environmental, Health and Safety (EHS)
The company’s animal health facility in Emeryville, California, has accreditation from the Association for Assessment and Accreditation of Laboratory Animal Care, a nonprofit organization that promotes the humane treatment of animals in science through voluntary accreditation and assessment programs.
The company and 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.
Patents and Proprietary Rights
Patents and pending patent applications covering Captisol and methods of making Captisol are owned by the company. The patents covering the Captisol product with the latest expiration date is set 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. The company has asserted U.S. Patents 8,410,077; 9,200,088; and 9,493,582 against Teva in connection with their attempt to obtain FDA approval to manufacture and sell a generic version of Evomela. The company also owns several patents and pending patent applications covering drug products containing Captisol as a component. Globally, the company owns approximately 440 issued patents covering all of the foregoing Captisol compositions, methods and related technology.
Seven Captisol patents in several families are listed in the Orange Book (Publication identifying drug products approved by the FDA based on safety and effectiveness) in connection with numerous prescription drugs on the market. These Captisol-enabled drugs include Nexterone (Baxter), Kyprolis (Amgen), Noxafil (Merck), Evomela (Acrotech/CASI), Baxdela (Melinta Therapeutics, Inc.) 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.
Patents protecting Kyprolis include those owned by Amgen and those owned by the company. The United States patent listed in the Orange Book relating to Kyprolis 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.
At the heart of the OmniAb technology stack are the company’s proprietary transgenic animals, including OmniRat, OmniMouse and OmniChicken, which have been genetically modified to generate antibodies with human sequences to facilitate development of human therapeutic candidates. OmniFlic and OmniClic are common light-chain rats and chickens, respectively, designed to generate bispecific antibodies. OmniTaur provides cow-inspired antibodies with unique structural characteristics for challenging targets.
The company has received patent protection on OmniAb animals and methods in over 40 jurisdictions, including the United States, multiple countries throughout Europe, Japan and China. These platform patents and applications owned by the company are expected to expire between 2028 and 2039 and partners are able to use the OmniAb patented technology to generate novel antibodies, which may be entitled to additional patent protection.
OmniAb’s business will include the Ab Initio Biotherapeutics, Inc. (Ab Initio) computational antigen design technology, Icagen’s ion channel technology, the xPloration high-throughput screening technology, in addition to the suite of OmniAb transgenic animals used for antibody discovery. Ab Initio owns a portfolio of issued patents and pending patent applications directed to SIRP-gamma polypeptides and apelin (APJ) receptor binding domains that includes issued patents in the United States and Europe and patent applications in the United States and multiple other countries. The patents and applications in Ab Initio’s owned portfolio are expected to expire between 2036 and 2040. Icagen, Inc. (Icagen) owns a portfolio of issued patent and pending patent applications directed to X-ray fluorescence-based detection of binding events and transport across barriers and related inventions, including 22 issued patents in the United States and patents issued in Europe, Japan and China, as well as pending patent applications in the U.S. and Europe. The patents and applications in Icagen’s portfolio are expected to expire between 2023 and 2040. xCella’s technology includes a microcapillary platform that can screen single B cells for specificity and bioactivity, which expand the company’s existing single- B cell assay capabilities in the OmniAb technology platform. xCella (xCella Biosciences, Inc.) owns a patent portfolio that includes three issued patents in the United States and pending patent applications in the U.S. and multiple other countries. The patents and applications in xCella’s owned portfolio are expected to expire between 2036 and 2040.
OmniAb’s intellectual property will remain with OmniAb following the planned separation of OmniAb into a new public company.
Ligand UK Development Limited
Under the terms of the company’s sale of Vernalis (R&D) Limited to HitGen in December 2020, Ligand retained a portfolio of fully-funded shots on goal, which include S65487, a Bcl-2 inhibitor, and S64315, an Mcl-1 inhibitor for the treatment of cancers, both of which are partnered with Servier in collaboration with Novartis AG (Novartis), VER250840 (an oral, selective Chk1 inhibitor for the treatment of cancer), and V158866, a novel, oral, selective fatty acid amide hydrolase (FAAH) inhibitor for CNS disorders, partnered with Neuritek Therapeutics. These programs and their IP are owned by Ligand UK Development Limited, which has a worldwide patent portfolio of over 200 granted patents in over 70 countries. This patent portfolio is mature, with expected expiry dates between 2022 and 2033.
Pelican Expression Technology Platform
The company acquired the Pelican Expression Technology platform through acquisition of Pfenex Inc. in October 2020. This acquisition brought a robust portfolio of patents and patent applications along with substantial know-how and trade secrets, which protect various aspects of the company’s core Pelican Expression Technology business. As of December 31, 2021, the company was the sole owner of a patent portfolio that consisted of over 200 patents and 50 pending patent applications worldwide that provide material coverage for its platform technology, licensed products and product candidates. The company’s the U.S. issued patents expire during the time period beginning in 2025 and ending in 2038. The company’s owned and exclusively licensed patent portfolio includes claims directed to methods for recombinant protein production and methods for rapid screening of an array of expression systems, tools for protein expression, such as P. fluorescens promoters, secretion leaders, plasmid maintenance systems, improved methods for non-standard amino acid incorporation and fusion partners for peptide production. In addition, the company’s IP covers methods for producing certain classes of proteins, such as cytokines, growth factors and antibody derivatives, as well as expression strains and methods for production, purification and formulation of certain vaccine antigens, peptides, therapeutic enzymes, human cytokines, etc.
The company’s trademarks, trade names and service marks referenced herein include Ligand, 3 Species, 1 License, Absolutely Omniab, Advasep, Animal Intelligence, BEPro, Biological Intelligence, Bonsity, Captisol, CyDex, Icagen, LTP, LTP Technology, Naturally Optimized Human Antibodies, OmniAb, OmniChicken, OmniClic, OmniDab, OmniDeep, OmniFlic, OmniMouse, OmniRat, OmniTaur, Pelican Expression Technology, PeliCRM, Pfenex Expression Technology, Picobodies, Three Species, One License, xCella Biosciences, XPloration and XRPro, which are protected under applicable intellectual property laws and are its property. All other trademarks, trade names and service marks, including Kyprolis, Evomela, Veklury, Livogiva, Zulresso, Rylaze, VAXNEUVANCE, Pneumosil, Minnebro, Baxdela, Carnexiv, Conbriza, Nexterone, Noxafil and Duavee, are the property of their respective owners.
Ligand Pharmaceuticals Incorporated was founded in 1987. The company was incorporated in 1987.