Alvotech (ICE: ALVO)

Alvotech Company Description

Alvotech, through its subsidiaries, develops and manufactures biosimilar medicines for patients worldwide.

The company’s platform is designed to enable it to execute the product development and scale-up process in-house: from identifying therapeutic areas and target product candidates with significant unmet patient and market need through R&D, leveraging gold-standard host cell lines, cell-culture processes and Good Manufacturing Practice (GMP) manufacturing, clinical testing, and regulatory approvals. In order to give its products global reach with local expertise, the company has formed strategic commercialization partnerships with leading pharmaceutical companies covering global markets. The company licenses its intellectual property to partners in exchange for milestone payments and royalties.

The company has eight product candidates in its portfolio and pipeline targeting serious diseases with unmet patient and market need. Product candidates in its pipeline address reference products treating autoimmune, eye, and bone disorders, as well as cancer.

Pipeline

Product selection

The company’s fully integrated capabilities provide it wide breadth and flexibility in deciding which biosimilar opportunities to pursue, optimizing the commercial, scientific and medical impact of each program as part of its portfolio.

The company’s platform is built for flexibility that may allow it to expand into other healthcare products areas, such as respiratory and primary care products.

Pipeline

Through its rigorous product selection and development platform, the company has been able to build a pipeline comprising five disclosed biosimilar products covering a variety of therapeutic areas, including autoimmune, eye, and bone disorders, as well as cancer. The company’s lead program, AVT02, a high concentration formulation biosimilar to Humira, received regulatory approval in the EEA, the U.K., Switzerland, Canada, Australia and Saudi Arabia. It is marketed in sixteen countries in Europe and in Canada and dossiers are under review in multiple countries, including in the United States. The company expects to launch AVT02, if approved by the FDA, in the United States on July 1, 2023. The company also has a second clinical program, AVT04, which uses the same SP2/0 host cell line as Stelara. In January 2023, the company announced that the FDA had accepted for review a BLA for AVT04. The company anticipates that the FDA’s review will be completed in the second half of 2023. The company directly or indirectly through its partners, also submitted marketing applications for AVT04 in the EU and in Japan in the second half of 2022. The company announced the initiation of clinical programs for AVT06 and AVT03 in July 2022 and the initiation of the pharmacokinetic study for AVT05 in January 2023. Beyond its registrational and clinical programs, the company has one additional product, AVT23, that is in late-stage development, and two undisclosed programs in pre-clinical development.

Programs

AVT02, High-Concentration Biosimilar to Humira

Humira (adalimumab) inhibits tumor necrosis factor (TNF), which is a protein in the body that can cause inflammation.

Since 2021, the company, directly or through its partners, received regulatory approval for AVT02 in the EEA, the U.K., Switzerland, Canada, Australia and Saudi Arabia. AVT02 is marketed in sixteen countries in Europe and in Canada. Dossiers are under review in multiple countries, including in the United States.

In February 2022, the FDA accepted the company’s BLA supporting interchangeability for review. In December 2022, the FDA issued a CRL for the February 2022 BLA requesting a correction of the same deficiencies identified on the August 2022 CRL with respect to the original BLA in order for approval.

In addition, the company successfully conducted a switching study to support a potential designation for interchangeability in the U.S. Pursuant to the U.S. AbbVie Agreement, the company settled all U.S. litigation related to AVT02 with AbbVie, and, subject to regulatory approval from the FDA, expects to launch AVT02 in the United States on July 1, 2023.

Pursuant to the various settlement agreements with AbbVie, the company resolved all intellectual property disputes with AbbVie relating to AVT02, except in Canada, in 2022.

AVT04, Proposed Biosimilar to Stelara

Stelara (ustekinumab) is a human IgG1k monoclonal antibody against the human interleukin-12 and -23 cytokines. Marketed by Janssen, Stelara is prescribed to treat a variety of inflammatory conditions including psoriatic arthritis, Crohn’s disease, ulcerative colitis, plaque psoriasis among other indications.

The company is using an SP2/0 host cell line, which is the same manufacturing host cell line as Stelara. In July 2021, the company announced the initiation of clinical studies for AVT04. A pharmacokinetic (PK) comparability study (AVT04-GL-101) is being conducted in healthy volunteers and is being conducted simultaneously in New Zealand and Australia. This is a single dose, 3-arm, parallel design to compare pharmacokinetic, safety, tolerability and immunogenicity of a single 45mg/0.5mL subcutaneous dose of AVT04, European-sourced Stelara (EU-Stelara) and U.S. sourced Stelara (US-Stelara). The study is being conducted in Australia and New-Zealand and the enrollment of all 294 participants was completed in the fourth quarter of 2021. The primary endpoints for this PK study are peak concentration (Cmax) and the total area under the curve (AUC0-inf). The secondary endpoints for the study include (but are not limited to) additional PK parameters, adverse events and clinical laboratory assessments, tolerability and immunogenicity parameters. In May 2022, the company reported positive topline results for the PK study for AVT04.

Simultaneously, the company is conducting a comparative, confirmatory efficacy and safety clinical study (AVT04-GL-301) in patients with chronic plaque psoriasis. The clinical study is conducted at approximately 30 investigational sites in five countries across Central and Eastern Europe. The enrollment (581 patients) was completed in September 2021. In May 2022, the company reported positive topline results for AVT04-GL-301.

In January 2023, the company announced that the FDA had accepted for review a BLA for AVT04. The company anticipates that the FDA’s review will be completed in second half of 2023. In February 2023, the company announced that the EMA had accepted a Marketing Authorization Application for AVT04. The company directly or indirectly through its partners, also submitted marketing applications for AVT04 in Japan and Canada in the second half of 2022.

AVT06, Proposed Biosimilar to Eylea

Eylea (aflibercept) is a recombinant fusion protein formulated for intravitreal administration consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1. Developed and marketed by Bayer and Regeneron, Eylea is prescribed to treat conditions including age-related macular degeneration, macular edema, and diabetic retinopathy.

Both the reference product as well as the company’s proposed biosimilar AVT06 are produced in recombinant Chinese hamster ovary cells.

The company originally planned to conduct the AVT06 trial, in part, in ten sites (for 44 patients) located in Ukraine and eight sites (for 19 patients) in Russia. Due to the Russia-Ukraine conflict, the company replaced these Ukrainian and Russian sites with sites in new countries with similar patient enrollment projections.

In July 2022, the company initiated the confirmatory clinical study for AVT06. The company targets the release of topline data in the second half of 2023.

AVT03, Proposed Biosimilar to both Xgeva and Prolia

Xgeva and Prolia have the same active ingredient, denosumab, but the products are approved for different indications, patient populations, doses and frequencies of administration. Denosumab is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL, receptor activator of nuclear factor kappa-B ligand.

Both the reference product as well as the company’s proposed biosimilar AVT03 are produced in recombinant Chinese hamster ovary cells.

AVT03 is in the pre-clinical phase and has been developed to have a high degree of analytical similarity to the originator. The company’s clinical program consists of a pharmacokinetic (PK) study in healthy volunteers and a confirmatory efficacy and safety study in patients with post-menopausal osteoporosis.

The company originally planned to conduct the AVT03 trial, in part, in five sites (for a projected 40 patients) in Ukraine.

In July 2022, the company announced the initiation of the pharmacokinetic (PK) study (AVT03-GL-P01) in healthy volunteers aimed to compare the pharmacokinetic, safety, tolerability and immunogenicity between AVT03 and the reference product Prolia after administration of 60mg single subcutaneous dose. The company targets the release of topline data in second half of 2023. In August of 2022, the company announced the initiation of a confirmatory patient study for AVT03. The company targets the release of topline data in 2024.

AVT05, Proposed Biosimilar to Simponi and Simponi Aria

Simponi / Simponi Aria (golimumab), inhibits TNF, which is a protein in the body that can cause inflammation. Simponi / Simponi Aria are prescribed to treat a variety of inflammatory conditions, including, RA, psoriatic arthritis, ulcerative colitis among others. Simponi is a sterile solution of golimumab antibody supplied for subcutaneous use. Simponi Aria injection is a sterile solution supplied for intravenous use. The company is developing both forms of the product. The company has developed AVT05 to match the host cell line used by the developer of the originator and it intends to pursue interchangeability designation. In January 2023, the company announced the initiation of its pharmacokinetic study for AVT05 in January 2023. The company targets the release of topline data in the first half of 2024.

AVT23 (also called BP001), Proposed Biosimilar to Xolair

Xolair (omalizumab) is an antibody that targets free IgE and is used to treat patients with allergic asthma, chronic spontaneous urticaria (CSU) and nasal polyp. Xolair, the only approved product containing omalizumab, was first approved in 2003.

AVT23 is in late-stage development. AVT23 will be produced using Biosana’s proprietary 3C process technology, a fully continuous operation to allow for highly productive, manufacturing. A pharmacokinetic (PK) comparability study has been completed showing that AVT23’s bioavailability, safety, tolerability and immunogenicity are comparable to those of Xolair.

Undisclosed Programs, AVT16 and AVT33

The company is in early phase development for two additional products that have not yet been publicly disclosed, AVT16, a proposed biosimilar to an immunology product, and AVT33, a proposed biosimilar to an oncology product.

Strategy

The company’s strategy is to leverage its integrated platform to develop and manufacture high quality biosimilars and to then work with its global network of partners to commercialize the portfolio and pipeline into markets around the world. The company is advancing multiple product candidates towards regulatory approval and intend to launch its portfolio and pipeline into over 90 markets around the world.

The company is advancing a portfolio and pipeline of 8 biosimilars and biosimilar candidates through the development and global regulatory process. The company’s portfolio and pipeline covers a variety of therapeutic areas, including autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer.

The company has formed a global network of strategic commercial partnerships to ensure that its products can reach the patients in geographies across the world. The company’s partners include Teva (US), STADA (EU), Yangtze (China), Fuji Pharma Co., Ltd (Japan), Cipla/Cipla Gulf/Cipla Medpro (Australia, New Zealand, South Africa/Africa), JAMP Pharma (Canada), DKSH (Taiwan, Hong Kong, Cambodia, Malaysia, Singapore, Indonesia, India, Bangladesh and Pakistan), YAS (Middle East and Africa), Abdi Ibrahim (Turkey), Kamada (Israel), Biosana (Australia, Netherlands, Singapore), and MegaLabs, Stein, Libbs, Tuteur and Saval (Latin America), Advanz Pharma (EEA, U.K., Switzerland, Canada, Australia and New Zealand), among others.

Platform

The company’s platform enables it to innovate and systematically develop and manufacture biosimilar medicines.

United States—Teva

License and Development Agreement with Teva Pharmaceuticals International GmbH (Teva)

In August 2020, the company entered into a license and development agreement with Teva which was amended in June 2021, and again in February 2023, for the commercialization of certain biosimilar products in certain territories (the LDA). Under the LDA, the company granted Teva an exclusive license, with the right to sublicense through multiple tiers, to use, import, commercialize, and market products containing AVT02, AVT04, AVT05, AVT06 and AVT16 in the United States and each of its territories, districts and possessions, including the Commonwealth of Puerto.

Product Supply Agreement with Teva Pharmaceuticals International GmbH

In addition to the LDA, the company entered into a product supply agreement with Teva in August 2020 for the exclusive manufacture and supply of each product during such product’s respective product supply term (the PSA).

Europe—STADA

From August to November of 2019, the company entered into similar license and supply agreements (out-license contracts) with STADA which were amended in March 2020, pursuant to which the company granted STADA exclusive licenses to import, commercialize and market certain products containing AVT02, AVT03, AVT04, AVT05, AVT06 and AVT16 in the European Union and certain other countries. Under the amended agreements, STADA also received joint ownership of certain of the company’s intellectual property covering such products in the EU and certain other countries under certain conditions.

In May 2021, the company entered into a second amendment of the AVT02 agreement to, among other things, expand the agreement to include an additional product and provide certain additional terms for the development, licensing and commercialization of such product. Under the amended agreement, the company granted STADA a perpetual, exclusive license to import, commercialize and market the additional product in the EU and certain other countries.

Japan – Fuji Pharma

On April 2, 2019, Alvotech and Fuji Pharma entered into a license agreement, as amended on June 23, 2020 to reflect a delay in the development process and therefore, among others, amended and restated the milestone payments, (the Fuji Pharma AVT04 License Agreement) and a supply agreement (the Fuji Pharma AVT04 Supply Agreement). Under the Fuji Pharma AVT04 License Agreement, Alvotech will develop AVT04 and compile and provide a dossier of data, information and know-how relating to AVT04 to Fuji Pharma. Alvotech retains full ownership of all intellectual property rights in AVT04 and the AVT04 dossier. Fuji Pharma has the exclusive right to use the dossier to obtain and maintain regulatory approvals for AVT04 and to import, finish, market, promote, sell and distribute AVT04 in Japan.

Canada – JAMP Pharma

JAMP Pharma has a portfolio with more than 290 molecules and is a leader in the pharmaceutical industry in Canada. In December 2019, Alvotech entered into five license and supply agreements with JAMP Pharma with respect to AVT02, AVT03, AVT04, AVT05 and AVT06. Under the terms of the agreements, Alvotech will develop the product candidates and provide the dossier of data, information and know-how relating to the relevant product candidate to JAMP Pharma. Alvotech retains full ownership of all intellectual property rights in the product candidates and the dossiers. JAMP Pharma has the exclusive right and obligation to use the dossier to try to obtain and maintain regulatory approvals for the relevant product and to market, sell, and distribute the products in Canada.

In January 2022, Health Canada granted marketing authorization to JAMP Pharma for AVT02. In April 2022, JAMP Pharma launched AVT02, under the trade name Simlandi, in Canada.

On August 29, 2022, Alvotech and JAMP Pharma entered into additional license and supply agreements on substantially the same terms and thereby expanded their partnership with two additional biosimilar candidates, AVT16 and AVT33.

In addition, Alvotech has partnerships with, among others, Yangtze (China), Cipla/Cipla Gulf/Cipla Medpro (Australia, New Zealand, South Africa/Africa), DKSH (Taiwan, Hong Kong, Cambodia, Malaysia, Singapore, Indonesia, India, Bangladesh and Pakistan), YAS (Middle East and Africa), Abdi Ibrahim (Turkey), Kamada (Israel), Biosana (Australia, Netherlands, Singapore), and MegaLabs, Stein, Libbs, Tuteur and Saval (Latin America), Advanz Pharma (EEA, the U.K., Switzerland, Canada, Australia and New Zealand).

Biosana for AVT23

Biosana. In December 2021, Alvotech entered into an exclusive global licensing agreement with Biosana Pharma (Biosana) for the co-development of AVT23, which will be produced using Biosana’s proprietary 3C manufacturing process technology. Under the terms of the agreement, Biosana will develop AVT23, compile part of the dossier of data, information and know-how related to AVT23 and provide the dossier to Alvotech.

Alvotech will conduct the comparative study and update the dossier, and, when completed, has the exclusive right (and, for the U.S., the U.K., France, Germany, Italy and Spain, the obligation) to use the dossier to obtain regulatory approvals and to market, promote, distribute and sell AVT23. In each case limited to the extent necessary and solely for the purpose of developing, registering, marketing, offering for sale, importing, storage, distributing, selling and using the property; and (ii) manufacturing the product, Biosana grants Alvotech exclusive, perpetual and irrevocable, assignable and sub-licensable rights to its intellectual property rights related to AVT23, including in the dossier, that existed prior to or are created during the collaboration; and the non-exclusive, perpetual and irrevocable, assignable and sub-licensable right with respect to the 3C manufacturing process.

Material Agreements, Partnerships and Suppliers

China Joint Venture

In September 2018, Alvotech created a 50-50 joint venture with the Joint Venture Partner to develop, manufacture and commercialize Alvotech’s biosimilar medicines in China and for the China market.

U.S. AbbVie Agreement

On March 8, 2022, Alvotech entered into the AbbVie U.S. Agreement with AbbVie Inc. and AbbVie Biotechnology Ltd with respect to AVT02 for the U.S. market. Pursuant to the settlement component of the AbbVie U.S. Agreement, the parties agreed to stipulate to the dismissal of all claims, counterclaims and potential claims in the pending litigation, with each party to bear its own fees and costs, in the U.S.

European AbbVie Agreement

On April 4, 2022, Alvotech entered into the European AbbVie Agreement with AbbVie Biotechnology Ltd with respect to the sale of AVT02 in Europe and selected markets outside of Europe (the European AbbVie Agreement). Under the licensing component of the European AbbVie Agreement, AbbVie granted Alvotech a license effective immediately to make, import, use, distribute, sell and offer for sale AVT02 in Europe and selected markets outside of Europe.

Intellectual Property

As of December 31, 2022, the company’s patent portfolio consists of several pending patent applications for composition of matter (formulations) related to its AVT02 product:

The company has patent applications entitled pharmaceutical formulations for adalimumab that are pending in Europe, Canada, Australia, Japan, New Zealand, China, and the United States, all owned by it. Any patents issuing from these pending applications would be expected to expire no earlier than 2038.

The company also has patent applications entitled Aqueous Formulations of TNF-alpha Antibodies in High Concentrations that are pending in Australia, New Zealand, Japan, Israel, Europe, China, the United States and Canada, all owned by it. Any patents issuing from these pending applications would be expected to expire no earlier than 2040.

Research and Development

The company’s research and development expenses included $180.6 million for the year ended December 31, 2022.

Regulatory Landscape

All of the company’s product candidates are subject to extensive pre- and post-market regulation in the United States by the FDA as biological products, or biologics. The Public Health Service Act, or PHSA, the Federal Food, Drug and Cosmetic Act, or FFDCA, and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, post-approval changes, and import and export of biologics. The company is subject to stringent and evolving United States and foreign laws, regulations, rules, contractual obligations, policies and other obligations related to data privacy and security, including the EU’s General Data Protection Regulation (EU GDPR) and the United Kingdom’s General Data Protection Regulation (UK GDPR).

History

Alvotech was founded in 2013. The company was incorporated in 2021.

Alvotech

Country	Luxembourg
Founded	2013
Industry	Drug Manufacturers - Specialty & Generic
Sector	Healthcare
Employees	999
CEO	Robert Wessman

Contact Details

Address: 9, Rue de Bitbourg Luxembourg, 1273 Luxembourg
Phone	354 422 4500
Website	alvotech.com

Stock Details

Ticker Symbol	ALVO
Exchange	Nasdaq Iceland
Fiscal Year	January - December
Reporting Currency	USD
ISIN Number	LU2458332611
SIC Code	2836

Key Executives

Name	Position
Robert Wessman	Chief Executive Officer, Founder and Executive Chairman
Faysal Kalmoua	Chief Operating Officer and Director
Joel Morales	Chief Financial Officer
Giedrius Zunda	Chief Technical Officer
Joseph E. McClellan	Chief Scientific Officer
Tanya Zharov	General Counsel
Anil Okay	Chief Commercial Officer
Ming Li	Chief Strategy Officer
Christina Siniscalchi	Chief Quality Officer