Seattle Genetics Inc Profile
Seagen Inc. operates as a biotechnology company that develops and commercializes targeted therapies to treat cancer.
The company is commercializing ADCETRIS, or brentuximab vedotin, for the treatment of certain CD30-expressing lymphomas, PADCEV, or enfortumab vedotin-ejfv, for the treatment of certain metastatic urothelial cancers, TUKYSA, or tucatinib, for the treatment of certain metastatic HER2-positive breast and colorectal cancers, and TIVDAK, or tisotumab vedotin-tftv, for the treatment of certain metastatic cervical cancers. The company is also advancing a pipeline of novel therapies for solid tumors and blood-related cancers designed to address unmet medical needs and improve treatment outcomes for patients. Many of the company’s programs, including ADCETRIS, PADCEV and TIVDAK, are based on its ADC technology that utilizes the targeting ability of monoclonal antibodies to deliver cell-killing agents directly to cancer cells.
The company’s strategy is to become a leading global oncology company developing and marketing targeted therapies for cancer. Key elements of the company’s strategy are to maximize the potential of its approved medicines through successful commercial execution, expand the number of patients eligible to receive its medicines by securing approvals of its commercial products in other countries, conduct clinical trials designed to support additional labels for its products, and develops new first-in-class or best-in-class medicines. The company seeks to commercialize its products either on its own as it expands its operations globally or through commercial partnerships. The company is deploying its internal research, clinical, development, regulatory and manufacturing expertise to advance and expand its deep pipeline of drug candidates aimed at gaining new product approvals. The company conducts internal research directed at identifying novel antigen targets, monoclonal antibodies and other targeting molecules, creating new antibody engineering techniques and developing new classes of stable linkers and cell-killing agents in support of its continued ADC innovation.
Medicines
ADCETRIS
ADCETRIS is an ADC targeting CD30, which is a protein located on the surface of cells and highly expressed in Hodgkin lymphoma, certain T-cell lymphomas as well as other cancers. ADCETRIS first received U.S. Food and Drug Administration, or FDA, approval in 2011 and is approved in a total of seven indications to treat Hodgkin lymphoma and certain T-cell lymphomas in various settings, including as frontline therapy for both adult and pediatric patients.
ADCETRIS has received approval in more than 75 countries worldwide. The company commercializes ADCETRIS in the U.S. and its territories and in Canada, and it collaborates with an affiliate of Takeda Pharmaceutical Company Limited, or Takeda, to develop and commercialize ADCETRIS on a global basis. Under this collaboration, Takeda has commercial rights in the rest of the world and pays the company a royalty. Takeda has received regulatory approvals for ADCETRIS as monotherapy or in combination with other agents in various settings for the treatment of patients with Hodgkin lymphoma or CD30-positive T-cell lymphomas in Europe and many countries throughout the rest of the world and is pursuing additional regulatory approvals.
PADCEV
PADCEV is an ADC targeting Nectin-4, a protein expressed on the surface of cells and highly expressed in bladder cancer, as well as other cancers. PADCEV was granted accelerated approval by the FDA in December 2019 for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery in the locally advanced or metastatic setting. FDA approval of PADCEV was supported by data from a single-arm pivotal phase 2 clinical trial called EV-201.
In July 2021, the FDA converted PADCEV's accelerated approval to regular approval in the U.S., in addition to granting regular approval for a new indication for adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and has previously received one or more prior lines of therapy. The conversion to regular approval was supported by the pivotal phase 3 clinical trial called EV-301 and the expanded indication was supported by data from the second cohort in the EV-201 trial. The FDA reviewed the application for regular approval under the Oncology Center of Excellence's, or OCE's, Real Time Oncology Review, or RTOR, pilot program.
In April 2022, the European Commission, or EC, approved PADCEV as monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a PD-1/L1 inhibitor. The approval is applicable in the European Union member states, as well as Iceland, Norway and Liechtenstein.
PADCEV is also approved in other countries, including Brazil, Canada, Japan, Great Britain and Switzerland, in previously treated metastatic urothelial cancer.
PADCEV is being co-developed and jointly commercialized with Astellas Pharma, Inc., or Astellas. In the U.S., the company and Astellas are jointly promoting PADCEV. The company records net sales of PADCEV in the U.S. and is responsible for all U.S. distribution activities. Outside the U.S., the company has commercialization rights in all other countries in North and South America, and Astellas has commercialization rights in the rest of the world, including Europe, Asia, Australia and Africa.
TUKYSA
TUKYSA is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2, a growth factor receptor overexpressed in certain cancers. HER2 mediates cell growth, differentiation and survival. Tumors that over-express HER2 are generally more aggressive and historically have been associated with poor overall survival, compared with HER2-negative cancers. In April 2020, TUKYSA received approval from the FDA in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
The company also participated in the Project Orbis initiative of the FDA OCE, which provides a framework for concurrent submission and review of oncology products among international partners. Under this program, the company has received approval in the U.S., Canada, Australia, Singapore, and Switzerland. In February 2021, the EC granted marketing authorization for TUKYSA in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens. This approval is valid in all countries of the European Union as well as Norway, Liechtenstein, Iceland and Northern Ireland. In Europe, the company has begun marketing TUKYSA in Austria, France, Germany and Switzerland. Additionally, in February 2021, the UK Medicines and Healthcare products Regulatory Agency, granted a Great Britain marketing authorization for TUKYSA.
In January 2023, TUKYSA received accelerated approval in combination with trastuzumab for adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. The approval was based on tumor response rate and durability of response from the phase 2 MOUNTAINEER clinical trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The company is responsible for commercializing TUKYSA in the U.S., Canada and Europe. In September 2020, the company entered into a license and collaboration agreement, or the TUKYSA Agreement, with Merck & Co., Inc., or Merck, pursuant to which it granted exclusive rights to Merck to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. The collaboration is intended to accelerate global availability of TUKYSA.
TIVDAK
TIVDAK is an ADC targeting tissue factor, a protein expressed on the surface of cells that has increased levels of expression on multiple solid tumors. The FDA granted accelerated approval of TIVDAK in September 2021 for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
TIVDAK is being co-developed with Genmab A/S, or Genmab, under an agreement in which the companies equally share all costs and profits for the product. Under a joint commercialization agreement, the company and Genmab co-promote TIVDAK in the U.S., and it record net sales of TIVDAK in the U.S. and is responsible for leading U.S. distribution activities. Outside the U.S., the company has commercialization rights in the rest of the world except for Japan, where Genmab has commercialization rights, and certain territories where Zai Lab has commercialization rights. In Europe, China, and Japan, the company and Genmab will equally share 50% of the costs associated with commercializing TIVDAK as well as any profits realized in these markets.
In September 2022, the company announced an exclusive collaboration and license agreement with Zai Lab for the development and commercialization of TIVDAK in mainland China, Hong Kong, Macau, and Taiwan.
Clinical Development and Regulatory Status
ADCETRIS (brentuximab vedotin)
Beyond its current labeled indications, the company is evaluating ADCETRIS as monotherapy and in combination with other agents in ongoing trials, including several potentially registration-enabling trials, such as the phase 3 ECHELON-3 clinical trial in relapsed or refractory diffuse large B-cell lymphoma.
In February 2022, the company announced that the phase 3 ECHELON-1 clinical trial demonstrated a statistically significant improvement in overall survival, or OS, (p=0.009) in patients with previously untreated advanced Hodgkin lymphoma following treatment with ADCETRIS in combination with chemotherapy.
In June 2022, the company announced results from a phase 3 clinical trial conducted by the Children's Oncology Group evaluating ADCETRIS in children and young adults with high-risk, previously untreated classical Hodgkin lymphoma. The trial showed ADCETRIS in combination with standard of care showed a clinically meaningful and statistically significant 59% reduction in the risk of disease progression or relapse, second malignancy or death and achieved superior event-free survival compared to the standard of care.
In December 2022, results were presented from two parts of a phase 2 trial (SGN35-027) evaluating ADCETRIS in combination with the PD-1 inhibitor nivolumab and standard chemotherapy agents doxorubicin and dacarbazine (AN+AD) for the frontline treatment of patients with classical Hodgkin lymphoma. Part B of the trial evaluated patients with advanced-stage disease, and Part C evaluated patients with early-stage disease.
PADCEV (enfortumab vedotin-ejfv)
In addition to jurisdictions where PADCEV is approved, applications are under review for approval in the previously treated metastatic urothelial cancer setting in other countries. In collaboration with Astellas the company is conducting or planning to conduct clinical trials across the spectrum of bladder cancer, including ongoing trials in frontline metastatic urothelial cancer and muscle invasive bladder cancer. The company is planning to conduct a trial in non-muscle invasive bladder cancer. In addition, the company is conducting a trial in a range of other solid tumors.
PADCEV is being investigated in first-line metastatic urothelial cancer and earlier stages of bladder cancer. The company and Astellas are conducting a phase 1b/2 clinical trial, called EV-103, that is a multi-cohort, open-label trial of PADCEV alone or in combination with other agents. The trial is evaluating safety, tolerability and activity in locally advanced and first- and second-line metastatic urothelial cancer, and was expanded to include muscle invasive bladder cancer, or MIBC.
In February 2020, based on the positive initial results of the dose escalation/Cohort A of the EV-103 trial, the FDA granted Breakthrough Therapy designation for PADCEV in combination with Merck's anti-PD-1 therapy pembrolizumab for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. In April 2020, the company announced that, based on discussions with the FDA, data from the randomized Cohort K in the EV-103 trial, along with other data from the EV-103 trial, could potentially support registration under the FDA's accelerated approval pathway. The primary endpoint is confirmed ORR. In October 2021, the company completed enrollment in Cohort K.
In July 2022, the company and Astellas announced positive topline results from the phase 1b/2 EV-103 clinical trial Cohort K evaluating PADCEV in combination with pembrolizumab as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer who are ineligible to receive cisplatin-based chemotherapy. In September 2022, the data were presented at the European Society for Medical Oncology Congress. In patients treated with PADCEV and pembrolizumab, results demonstrated a 64.5% confirmed ORR (95% CI: 52.7 to 75.1) per blinded independent central review, or BICR, the primary endpoint of Cohort K, with 10.5% of patients experiencing a complete response and 53.9% of patients experiencing a partial response.
In addition to the potential accelerated approval pathway based on the EV-103 trial, the company is conducting a global, registrational phase 3 clinical trial, called EV-302, in frontline metastatic urothelial cancer in collaboration with Astellas and Merck. The company, Astellas and Merck are jointly funding EV-302 and the trial is being conducted by it. EV-302 is an open-label, randomized phase 3 clinical trial evaluating the combination of PADCEV and pembrolizumab versus chemotherapy alone in patients with previously untreated locally advanced or metastatic urothelial cancer. In November 2022, the company completed enrollment in the EV-302 trial. For this trial, the company has initiated an extension study in China which continues to enroll.
In April 2020, the company and Astellas entered into an agreement with Merck to evaluate PADCEV in MIBC. Merck has amended its ongoing phase 3 KEYNOTE-905/EV-303 registrational trial in cisplatin-ineligible patients with MIBC to include an arm evaluating PADCEV in combination with pembrolizumab. In October 2020, the company and Astellas entered into an agreement with Merck to evaluate PADCEV in combination with pembrolizumab in a phase 3 clinical trial, called KEYNOTE-B15/EV-304, to be conducted by Merck in cisplatin-eligible patients with MIBC. This trial was initiated in the first quarter of 2021.
In January 2022, the company enrolled the first patient in a phase 1 clinical trial, called EV-104, evaluating PADCEV in patients with BCG unresponsive non-muscle invasive bladder cancer.
In January 2020, the company and Astellas also initiated a phase 2 clinical trial, called EV-202, to evaluate PADCEV monotherapy in solid tumors that have high-levels of Nectin-4 expression, including non-small cell lung, head and neck, gastric/esophageal and breast cancers. Astellas is conducting the trial and has obtained topline results in some cohorts.
TUKYSA (tucatinib)
The company is conducting a broad clinical development program for TUKYSA including ongoing and planned trials in earlier lines of breast cancer and in other HER2-positive cancers. The positive results of the HER2CLIMB trial served as the basis for approval in the U.S., Canada, the European Union as well as other countries. Merck is co-funding a portion of the TUKYSA global development plan.
In December 2021, the company presented new data at the San Antonio Breast Cancer Symposium from exploratory analyses from the pivotal HER2CLIMB trial showing that improvement in OS was maintained after an additional 15.6 months of follow-up when TUKYSA was combined with trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer who had stable or active brain metastases. After a median follow-up of 29.6 months, the TUKYSA regimen improved OS for patients with brain metastases by 9.1 months compared to trastuzumab and capecitabine alone (21.6 months vs. 12.5 months) (HR: 0.60; [95% CI: 0.44, 0.81]).
In October 2019, the company initiated a phase 3 randomized trial, called HER2CLIMB-02, evaluating TUKYSA versus placebo, each in combination with T-DM1, for patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. In June 2022, the company completed enrollment in the HER2CLIMB-02 trial and expects to report topline data in the first half of 2023. For this trial, the company has initiated an extension study in China which continues to enroll.
The company is supporting a U.S. cooperative group, the Alliance for Clinical Trials in Oncology, that is conducting a phase 3 randomized trial, called CompassHER2 RD, which is evaluating TUKYSA in combination with T-DM1 in the adjuvant setting for patients with high-risk, HER2-positive breast cancer.
The company is also conducting a phase 2 clinical trial, called HER2CLIMB-04, evaluating TUKYSA in combination with trastuzumab deruxtecan in previously treated locally-advanced or metastatic HER2-positive breast cancer.
The company has also initiated a phase 3 clinical trial, called HER2CLIMB-05, evaluating TUKYSA compared to placebo in combination with trastuzumab and pertuzumab in the frontline maintenance setting for patients with metastatic HER2-positive breast cancer.
The company has conducted a pivotal phase 2 clinical trial, called MOUNTAINEER, evaluating TUKYSA in combination with trastuzumab in patients with HER2-positive, RAS wild-type metastatic colorectal cancer after treatment with first- and second-line standard-of-care therapies. In July 2022, the company presented positive results from the MOUNTAINEER trial investigating TUKYSA in combination with trastuzumab in patients with previously treated HER2-positive metastatic colorectal cancer at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer. The combination of TUKYSA and trastuzumab was generally well-tolerated with durable responses in patients assigned to receive the combination demonstrating a 38.1% confirmed response rate after a median duration of follow-up of 20.7 months.
In addition, the company is conducting a phase 3 clinical trial, called MOUNTAINEER-03, in combination with trastuzumab and mFOLFOX6 in first-line HER2-positive metastatic colorectal cancer, which is intended to serve as a confirmatory trial and potentially support future global regulatory submissions. The company has also initiated a phase 1b trial evaluating TUKYSA in combination with trastuzumab and oxaliplatin based chemotherapy in first-line HER2-positive unresectable or metastatic colorectal, gastric, esophageal and gallbladder cancers.
TIVDAK (tisotumab vedotin-tftv)
In collaboration with Genmab, the company is developing TIVDAK for metastatic cervical cancer and are evaluating it as a potential therapy in other solid tumors. The FDA granted accelerated approval of TIVDAK in September 2021 for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
In January 2021, the company and Genmab initiated a phase 3 clinical trial, called innovaTV 301, to evaluate TIVDAK compared to chemotherapy in patients with recurrent or metastatic cervical cancer who have received one or two prior lines of therapy. innovaTV 301 is intended to support global regulatory applications for potential approvals in regions where innovaTV 204 does not support approval and to serve as a confirmatory trial in the U.S.
The company is conducting a phase 2 clinical trial, called innovaTV 205, evaluating TIVDAK as monotherapy and in combination with certain other anti-cancer agents for first- and second-line treatment of patients with recurrent or advanced cervical cancer. Additionally, in June 2022, the company announced interim data from the innovaTV 205 trial, which included data evaluating TIVDAK in combination with pembrolizumab in patients with recurrent or metastatic cervical cancer who have not received prior systemic therapy. The company expects to report additional data in the second half of 2023.
The company is conducting a phase 2 clinical trial, called innovaTV 207, for patients with relapsed, locally advanced or metastatic solid tumors. In February 2022, initial data from the innovaTV 207 phase 2 trial of TIVDAK in solid tumors was presented at the Multidisciplinary Head and Neck Cancers Symposium.
Disitamab Vedotin
Effective in September 2021, the company and RemeGen entered into an exclusive license agreement to develop and commercialize disitamab vedotin, a novel HER2-targeted ADC, which has shown anti-tumor activity in several solid tumor types across a spectrum of HER2 levels, including urothelial, gastric and breast cancer, in all countries outside of RemeGen's territory of Asia, excluding Japan and Singapore. The company has a broad clinical development program planned, including an ongoing phase 2 clinical trial evaluating disitamab vedotin as monotherapy in previously treated HER2-expressing metastatic urothelial cancer and a phase 3 clinical trial evaluating disitamab vedotin in combination with pembrolizumab in first-line treatment for HER2-expressing metastatic urothelial cancer that is expected to initiate in 2023.
Ladiratuzumab Vedotin
The company is developing ladiratuzumab vedotin, or LV, an ADC targeting LIV-1, which is being evaluated in phase 1 and phase 2 clinical trials both as monotherapy and in combination with other agents for patients with metastatic breast cancer and select solid tumors with high LIV-1 expression. The company expects to report initial data in solid tumors in the second half of 2023. In September 2020, the company and Merck entered into a license and collaboration agreement, or the LV Agreement, under which the companies will jointly develop and share future costs and profits worldwide for LV.
Other clinical and early-stage product candidates
The company is advancing a pipeline of early-stage clinical candidates as well as multiple preclinical and research-stage programs that employ its proprietary technologies.
In November 2022, the company reported interim phase 1 monotherapy results for SGN-B6A at the Society for Immunotherapy of Cancer’s, or SITC's, Annual Meeting.
The company is also developing SGN-B7H4V, an ADC which it is evaluating in a phase 1 clinical trial in certain solid tumors, including breast, endometrial and ovarian cancer. The company expects to report initial data in the second half of 2023.
In September 2022, the company entered into an agreement with LAVA Therapeutics N.V., or LAVA, to develop and commercialize LAVA-1223, also known as SGN-EGFRd2, a preclinical gamma delta bispecific T-cell engager for EGFR-expressing solid tumors. The company received an exclusive global license for SGN-EGFRd2 and the opportunity to exclusively negotiate rights to apply LAVA's proprietary Gammabody platform on up to two additional tumor targets. The company is targeting filing an IND for SGN-EFGRd2 in 2023.
In March 2022, the company entered into a collaboration with Sanofi to develop and potentially commercialize multiple novel ADCs. The agreement is an exclusive collaboration that will utilize Sanofi's proprietary monoclonal antibody technology and its proprietary ADC technology for up to three cancer targets. The initial ADC is targeting CEACAM5, a protein highly expressed in certain tumor types, such as colorectal, gastric, pancreatic and lung cancer. The company is targeting filing an IND for the initial ADC in 2023.
In January 2023, the company enrolled the first patient was dosed in a phase 1 trial of SGN-BB228, a CD228x4-1BB bispecific molecule, in advanced melanoma and other solid tumors.
Antibody-Drug Conjugate (ADC) Technology
ADCETRIS, PADCEV, TIVDAK and many product candidates in the company’s clinical-stage pipeline utilize its ADC technology. The company’s ADCs utilize monoclonal antibodies that internalize within target cells after binding to a specified cell-surface receptor.
The company’s most advanced ADCs, including ADCETRIS, PADCEV, TIVDAK, disitamab vedotin, and ladiratuzumab vedotin, use its proprietary auristatin-based ADC technology. Auristatins are microtubule disrupting agents. The company owns or holds exclusive or partially-exclusive licenses to multiple issued patents and patent applications covering its ADC technology.
Sugar-Engineered Antibody (SEA) Technology
The company’s proprietary SEA technology is a method to selectively reduce fucose incorporation in monoclonal antibodies as they are produced in cell line-based manufacturing. The company’s SEA technology is a novel approach to modify the activity of monoclonal antibodies that is complementary to its ADC technology.
The company has product candidates that are being evaluated in phase 1 clinical trials that utilize its SEA technology, including SEA-TGT and SEA-CD70. These agents are targeted at a variety of cancer types.
Other Technologies
In addition, the company utilizes other technologies designed to maximize antitumor activity and reduce toxicity of antibody-based therapies. For ADCs, the company screens and selects antibodies that bind to antigens that are differentially expressed on tumor cells versus vital normal tissues, rapidly internalized within target cells and has potent anti-tumor activity in preclinical models. For its SEA technology the company produces antibodies that demonstrate potent anti-tumor activities by virtue of ADCC, or through additional immune stimulatory mechanisms that are triggered by the enhanced binding potency to innate immune cells. The company’s ADCs utilize native or engineered conjugation sites to optimize drug attachment. In some cases, the company evaluates the use of its monoclonal antibodies and ADCs in combination with conventional chemotherapy and other anticancer agents, which may result in increased antitumor activity.
Research Programs
In addition to its pipeline of product candidates and technologies, the company has internal research programs directed toward developing new classes of potent anti-tumor and immune stimulatory agents and new ADC linkers, the identification of novel drug targets and monoclonal antibodies, and advancing its antibody engineering initiatives.
New Tumor Cell-Killing Agents: The company continues to identify and study new agents with anti-tumor mechanisms of action that will provide pipeline diversity and complement the auristatins that it uses in its ADC technology. The company also seeks to develop new drugs that are designed to activate the host immune system by targeting key immune stimulatory pathways that can mediate innate or adaptive anti-tumor immune responses.
New Drug Linkers: The company is conducting research with the intent to develop new ADC linkers that are designed to provide the appropriate stability in the bloodstream and drug release characteristics to effectively target cancer cells and improved cancer cell selectivity and tolerability.
Novel Monoclonal Antibodies and Antigen Targets: The company is actively engaged in internal efforts to identify and develop monoclonal antibodies, and other therapeutic molecules, to target tumor antigens and important tumor or immune pathways. For ADCs, the company focuses on drug targets that are highly expressed on the surface of cancer cells that have the appropriate expression, distribution and internalization properties that make them desirable as monoclonal antibody or ADC targets. The company identifies targets that play key roles in anti-tumor innate or adaptive immune responses and identify antibodies and other therapeutic molecules to stimulate an anti-tumor immune response. The company supplements these internal efforts by evaluating opportunities to in-license targets and antibodies from academic groups and other biotechnology and pharmaceutical companies, such as its ongoing collaborations with Astellas and Genmab.
Antibody Engineering: The company has substantial internal expertise in antibody engineering, including humanization, binding affinity optimization, enhancement of immunological function by blocking fucosylation, as well as engineering antibodies to improve drug linkage sites for use with its ADC technology.
Corporate Collaborations
Takeda ADCETRIS Collaboration
The company has an agreement with Takeda for the global co-development of ADCETRIS and the commercialization of ADCETRIS by Takeda in its territory. The company has commercial rights for ADCETRIS in the U.S. and its territories and in Canada.
Astellas PADCEV Collaboration
The company has a collaboration agreement with Agensys, Inc., which subsequently became an affiliate of Astellas, to jointly research, develop and commercialize ADCs for the treatment of several types of cancer. The collaboration encompasses combinations of the company’s ADC technology with fully-human antibodies developed by Astellas to proprietary cancer targets.
In 2018, the company and Astellas entered into a joint commercialization agreement to govern the global commercialization of PADCEV:
In the U.S., the company and Astellas jointly promote PADCEV. The company records sales of PADCEV in the U.S. and are responsible for all the U.S. distribution activities.
Outside the U.S., the company has commercialization rights in all countries in North and South America, and Astellas has commercialization rights in the rest of the world, including Europe, Asia, Australia and Africa.
Merck TUKYSA Collaboration
In September 2020, the company entered into the TUKYSA Agreement with Merck. Under the TUKYSA Agreement, the company granted Merck exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. Merck is responsible for marketing applications for approval in its territory, supported by the positive results from the HER2CLIMB clinical trial. The company retained commercial rights in, and will record sales in, the U.S., Canada and Europe. Merck also agreed to co-fund a portion of the TUKYSA global development plan, which encompasses several ongoing and planned trials across HER2-positive cancers. The company owes Array Biopharma Inc., or Array, an affiliate of Pfizer, a portion of any non-royalty payments received from sublicensing TUKYSA rights, as well as a low double-digit royalty based on net sales of TUKYSA by it, and will owe a single-digit royalty based on net sales of TUKYSA by Merck in its territories.
Genmab TIVDAK Collaborations
The company has a collaboration agreement with Genmab to develop and commercialize ADCs targeting tissue factor, under which it previously exercised a co-development option for TIVDAK. Under this collaboration, the company and Genmab are co-funding all development costs for TIVDAK.
In October 2020, the company and Genmab entered into a joint commercialization agreement to govern the global commercialization of TIVDAK:
In the U.S., the company and Genmab co-promote TIVDAK. The company record sales of TIVDAK in the U.S. and is responsible for leading U.S. distribution activities.
Outside the U.S., the company has commercialization rights in the rest of the world except for Japan, where Genmab has commercialization rights, and certain territories where Zai Lab has commercialization rights.
RemeGen Disitamab Vedotin License Agreement
Effective in September 2021, the company and RemeGen entered into an exclusive worldwide licensing agreement to develop and commercialize disitamab vedotin, a novel HER2-targeted ADC. RemeGen retains development and commercialization rights for Asia, excluding Japan and Singapore.
In September 2022, the company announced an exclusive collaboration and license agreement with Zai Lab for the development and commercialization of TIVDAK in mainland China, Hong Kong, Macau, and Taiwan.
Merck LV Collaboration
In September 2020, the company entered into the LV Agreement with a subsidiary of Merck. Under the terms of the LV Agreement, the company granted Merck a co-exclusive worldwide development and commercialization license for LV and agreed to jointly develop and commercialize LV on a worldwide basis.
ADC License Agreements
The company has license agreements for its ADC technology with a number of biotechnology and pharmaceutical companies. Under these agreements, which the company has entered into in the ordinary course of business, it has granted research and commercial licenses to use its technology, most often in conjunction with the licensee's technology. In certain agreements, the company also has agreed to conduct limited development activities and to provide other materials, supplies, and services to its licensees during a specified term of the agreement.
In 2019, Genentech received accelerated approval from the FDA for Polivy (polatuzumab vedotin-piic), an ADC that uses the company’s technology, to treat patients with relapsed or refractory diffuse large B-cell lymphoma. In August 2020, GSK plc, or GSK, received accelerated approval from the FDA and conditional marketing authorization from the EC for Blenrep (belantamab mafodotin-blmf), an ADC developed by GSK that uses the company’s technology, for the treatment of patients with relapsed or refractory multiple myeloma who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulatory agent. In November 2022, GSK announced that it had initiated the process for withdrawal of U.S. marketing authorization for Blenrep following a request by the FDA. The product candidates being developed under the company’s other ADC license agreements are at various stages of clinical and preclinical development.
In-license Agreements
The company has in-licensed antibodies, targets and enabling technologies from pharmaceutical and biotechnology companies and academic institutions for use in its pipeline programs and ADC technology, including the following:
Array BioPharma, Inc.: The company is a party to a license agreement with Array, which was acquired by Pfizer in July 2019. Pursuant to the license agreement, Array has granted the company an exclusive license to develop, manufacture and commercialize TUKYSA.
Other Licenses: Under the terms of in-license agreements related to its pipeline programs, the company would potentially owe development, regulatory, and sales-based milestones, and royalties on net sales of certain approved products.
Patents and Proprietary Technology
The company’s owned and licensed patents and patent applications are directed to ADCETRIS, PADCEV, TUKYSA, TIVDAK, its product candidates, monoclonal antibodies, its ADC and SEA technologies and other antibody-based and/or enabling technologies. The company commonly seeks patent claims directed to compositions of matter, including antibodies, ADCs, and drug-linkers containing highly potent cell-killing agents, as well as methods of using such compositions.
The company maintains patents and prosecute applications worldwide for technologies that it has out-licensed, such as its ADC technology. Similarly, for partnered products and product candidates, such as ADCETRIS, PADCEV, TUKYSA, TIVDAK, disitamab vedotin and LV, the company seeks to work closely with its development partners to coordinate patent efforts, including patent application filings, prosecution, term extension, defense and enforcement. As its products and product candidates advance through research and development, the company seeks to diligently identify and protect new inventions, such as combination therapies, improvements to methods of manufacturing, and methods of treatment. The company also works closely with its scientific personnel to identify and protect new inventions that could eventually add to its development pipeline.
The company owns or has rights to the following patents relating to its products and its pipeline (in addition to certain patents covering its early-stage product candidates):
For ADCETRIS and the company’s related ADC technology, it owns thirteen patents in the United States and Europe that will expire between 2023 and 2031.
For PADCEV and its related ADC technology, the company owns, co-owns or has licensed rights to fourteen patents in the United States and Europe that will expire between 2023 and 2031. Of these patents, the company owns or co-owns twelve patents and have licensed rights to two patents.
For TUKYSA, the company owns or has licensed rights to eleven patents in the United States and Europe that will expire between 2024 and 2038. Of these patents, the company owns one patent and has licensed rights to ten patents.
For TIVDAK and the company’s related ADC technology, it owns or has licensed rights to ten patents in the United States and Europe that will expire between 2023 and 2036. Of these patents, the company owns four patents and has licensed rights to six patents.
For disitamab vedotin and its related ADC technology, the company owns or has licensed rights to seven patents in the United States and Europe that will expire between 2023 and 2034. Of these patents, the company owns four patents and has licensed rights to three patents.
For LV and its related ADC technology, the company owns or has licensed rights to eight patents in the United States and Europe that will expire between 2023 and 2032. Of these patents, the company owns seven patents and has licensed rights to one patent.
Government Regulation
The company must obtain approval of its product candidates from the FDA before it can begin marketing them in the United States. Similar approvals are also required in other countries.
Manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including current Good Manufacturing Practices, or cGMP, which impose certain procedural and documentation requirements upon the company and its third-party manufacturers.
The company and Takeda have a collaboration with Ventana Medical Systems, Inc., or Ventana, under which Ventana is working to develop, manufacture and commercialize a companion diagnostic test to measure CD30 expression levels in tissue specimens.
As the company continues to expand its footprint and activities internationally, its exposure to compliance risks under the U.S. Foreign Corrupt Practices Act and other similar laws will likewise increase.
In addition, because the company participates in the Medicaid drug rebate program, the company must make its products available to authorized users of the Federal Supply Schedule of the General Services Administration. This requires compliance with additional laws and requirements, including offering its products at a reduced price to federal agencies, including the United States Department of Veterans Affairs and the United States Department of Defense, the Public Health Service and the Indian Health Service. The company is also required to offer discounted pricing to certain eligible not for profit entities that are eligible for 340B pricing under the Public Health Services Act.
Manufacturing
ADCETRIS
AbbVie Biotechnology Ltd. (AbbVie): The company has a development and supply agreement with AbbVie to manufacture developmental, clinical and commercial quantities of anti-CD30 monoclonal antibody, which is a component of ADCETRIS. The agreement generally provides for the supply by AbbVie and the purchase by the company of such anti-CD30 monoclonal antibody.
PADCEV
Astellas or its affiliates are responsible for overseeing the initial manufacturing supply chain for PADCEV for development and commercial use. However, the company is responsible for packaging and labeling in countries in which it sells PADCEV. In addition, the company is in the process of establishing a second source manufacturing supply chain, through a combination of internal manufacturing capacity and third parties.
TUKYSA
With respect to TUKYSA, the company relies on multiple contract manufacturers and other third parties to perform manufacturing services for us, including Sterling Pharma Solutions Limited, or Sterling, for production of the starting materials for TUKYSA, Esteve Quimica, S.A., or Esteve, to produce the active pharmaceutical ingredient and Hovione FarmaCiencia SA, or Hovione, to complete spray drying. The company has multiple contract manufacturers to produce the tablets for TUKYSA.
Sterling. The company has a commercial supply agreement with Sterling to manufacture starting materials for TUKYSA. The agreement provides that the company will purchase starting materials pursuant to rolling forecasts and will purchase a minimum percentage of its requirements for the starting materials from Sterling. The agreement will remain in effect until 2025, after which it will continue automatically for up to two additional years subject to termination by either party giving written notice to the other party.
Esteve: The company’s commercial supply agreement with Esteve provides that it will order the active pharmaceutical ingredient for TUKYSA pursuant to rolling forecasts and will purchase a minimum percentage of its requirements for the active pharmaceutical ingredient from Esteve. The agreement will remain in effect until 2025, subject to termination by the company giving written notice to Esteve, after which it will automatically renew subject to termination by either party by giving written notice to the other party.
Hovione: The company has a commercial supply agreement with Hovione to manufacture the tucatinib spray-dried dispersion or drug product intermediate for TUKYSA. The agreement will remain in effect until 2026, followed by successive automatic two-year renewals.
TIVDAK
The company also relies on multiple contract manufacturers and other third parties to perform manufacturing services for it with respect to TIVDAK.
Commercial Operations
The company has allocated commercial resources, including sales, marketing, supply chain management and reimbursement capabilities, to commercialize ADCETRIS and PADCEV in the U.S. and Canada, TUKYSA in the U.S., Europe and Canada, and TIVDAK in the U.S. The markets for the company’s products in their approved indications are addressable with a targeted sales and marketing organization. Astellas jointly commercializes PADCEV with the company in the U.S. In addition, Genmab jointly commercializes TIVDAK with the company in the U.S.
In the U.S., the company sells ADCETRIS, PADCEV, TUKYSA, and TIVDAK through a limited number of specialty distributors. Three of the company’s major distributors, together with entities under their common control—AmerisourceBergen Corporation, Cardinal Health, Inc., and McKesson Corporation—each accounted for 10% or more of the company’s total net product sales in 2022. Healthcare providers purchase ADCETRIS, PADCEV, TUKYSA, and TIVDAK through these specialty distributors and the product is drop shipped directly to the healthcare provider. In addition to specialty distributors, the company sells TUKYSA to a limited number of specialty pharmacies.
ADCETRIS, PADCEV and TIVDAK are infused products and generally shipped directly to healthcare providers and facilities for administration to patients. TUKYSA is an oral product ordered by prescription and typically dispensed to patients by the network specialty pharmacies, at physician in-office dispensing sites, or by hospital/Integrated Delivery Network pharmacies.
In Europe, the company has allocated commercial resources, including sales, marketing, supply chain management, and reimbursement capabilities to enable and execute launches across key markets in Europe. Hospitals in Europe can purchase TUKYSA directly from the company or indirectly from wholesale distributors. In European countries where the company has not established its own sales force, TUKYSA can be accessed through distribution partners.
Research and Development
The company’s research and development expenses in 2022 were $1.3 billion.
History
The company was founded in 1997. The company was incorporated in Delaware in 1997. It was formerly known as Seattle Genetics, Inc. and changed its name to Seagen Inc. in 2020.
