Paratek Pharmaceuticals Profile
Paratek Pharmaceuticals, Inc. operates as a commercial-stage biopharmaceutical company.
The company focuses on the development and commercialization of novel life-saving therapies for life-threatening diseases or other public health threats for civilian, government and military use.
The company’s United States, or U.S., Food and Drug Administration, or FDA, approved commercial product, NUZYRA (omadacycline) is a once-daily oral and intravenous antibiotic for the treatment of adult patients with community-acquired bacterial pneumonia, or CABP, and acute skin and skin structure infections, or ABSSSI, caused by susceptible pathogens. The company retains worldwide commercial rights to omadacycline, with the exception in the People’s Republic of China, Hong Kong, Macau and Taiwan, where it has entered into a collaboration agreement with Zai Lab (Shanghai) Co., Ltd., or Zai. The National Medical Products Administration, or NMPA, of China approved NUZYRA for the treatment of adult patients with CABP and ABSSSI in December 2021. China's National Healthcare Security Administration added the intravenous formulation of NUZYRA (omadacycline) to the country's National Reimbursement Drug List for the treatment of CABP and ABSSSI in January 2023, resulting in millions of patients gaining access to this once daily broad-spectrum antibiotic.
SEYSARA (sarecycline) is an FDA-approved product which the company has exclusively licensed in the U.S. and the People’s Republic of China, Hong Kong, Macau and Taiwan, certain rights to Almirall, LLC, or Almirall. SEYSARA is currently being marketed by Almirall in the U.S. as a once-daily oral therapy for the treatment of moderate to severe acne vulgaris. With respect to its technology as it relates to sarecycline, the company retains development and commercialization rights in all countries other than the U.S., the People's Republic of China, Hong Kong, Macau and Taiwan, and in February 2020,it exclusively licensed from Almirall certain technology owned or in-licensed by Almirall or its affiliates that is necessary or useful to develop or commercialize sarecycline outside of the U.S. Almirall plans to develop sarecycline for acne in China, with a submission to the NMPA expected in 2023, according to Almirall.
NUZYRA
NUZYRA has the potential to become the primary choice of physicians for use as a once-daily broad-spectrum monotherapy oral and IV antibiotic for ABSSSI, CABP and other serious community-acquired bacterial infections where resistance is of concern. NUZYRA is used in the emergency room, hospital, and community care settings. The company has designed NUZYRA to provide potential advantages over existing antibiotics, including activity against resistant bacteria, broad-spectrum antibacterial activity, oral and IV formulations with once-daily dosing, no dosing adjustments for patients on concomitant medications and a generally safe and well-tolerated profile. NUZYRA also has the potential to be used as a once-daily oral and IV antibiotic for the treatment of non-tuberculous mycobacteria, or NTM, and both the treatment and prophylaxis of pulmonary anthrax, as a priority medical countermeasure.
As of December 31, 2022, the company had conducted more than 30 Phase 1 studies of omadacycline to characterize the effects of the drug on humans, including how it is absorbed, metabolized, and excreted. These Phase 1 studies also included evaluation in special populations, such as patients with hepatic and renal failure. The company has also conducted three successful Phase 3 clinical studies. The company’s first two Phase 3 clinical studies were for the treatment of ABSSSI (OASIS-1) and CABP (OPTIC). Both studies utilized initiation of IV therapy with transitions to oral-based treatment on clinical response. The company’s third Phase 3 clinical study (OASIS-2) was an oral-only administration of omadacycline in ABSSSI compared to oral-only linezolid. All three Phase 3 clinical studies resulted in omadacycline demonstrating positive efficacy results and a generally safe and well tolerated profile. These data formed the basis of approval for NUZYRA in the U.S. received in October 2018. The FDA subsequently approved the company’s supplemental new drug application, or sNDA, for the oral-only loading dose regimen for patients diagnosed with CABP in May 2021. The sNDA included the results of a study to show that an oral-only loading dose regimen has a comparable pharmacokinetics, or PK, profile to the approved IV loading dose regimen in patients with CABP that was established in the OPTIC study.
In October 2018, the company submitted a Market Authorization Application, or MAA, to the European Medicines Agency, or the EMA, for the treatment of adults with ABSSSI and CABP caused by susceptible bacteria. Based on the review of the data and the application, the EMA recommended approval for NUZYRA for the treatment of ABSSSI but not for CABP. The EU represents a modest market opportunity for ABSSSI and CABP compared to that in the U.S.
Biomedical Advanced Research and Development Authority Contract
In December 2019, the company entered into the BARDA contract, which is a five-year contract with an option to extend to ten years. The BARDA contract supports the development of NUZYRA for the treatment of pulmonary anthrax, FDA post-marketing requirements, or PMRs, associated with the initial NUZYRA approval, and the ability for BARDA to procure up to 10,000 treatment courses of NUZYRA for use against potential biothreats.
The company has made significant progress in the pulmonary anthrax development program under the amended BARDA Bioshield contract. The company completed the first Animal Rule pilot efficacy study in 2022, which revealed that all three doses of omadacycline demonstrated one-hundred percent efficacy; all animals survived in an anthrax treatment model during which all non-treated animals died by Day 3. Three PK studies in rabbits and three more in non-human primates have also been completed. In addition, the company has evaluated minimum inhibitory concentrations, or MICs, of omadacycline against over 130 anthrax strains.
Together with BARDA, the company also continues to advance its efforts to onshore the manufacturing of NUZYRA to the U.S. The company has completed the knowledge transfer and development stage of its manufacturing process for the active pharmaceutical ingredient, or API, of omadacycline to its U.S. onshoring partners and is in the engineering stage of the initiative. The company has completed knowledge transfer and the initiation of the process development work for production of vials. U.S.-based commercial supply production of tablets was implemented in 2022 and it anticipates these vials will be available by 2024.
The BARDA contract contains a number of terms and conditions that are customary for government contracts of this nature, including provisions giving the government the right to terminate the contract at any time for its convenience.
Development of Omadacycline in Other Therapeutic Areas
Non-Tuberculous Mycobacteria Abscessus
The company has discussed trial designs and potential registration pathways with the FDA to determine the efficacy and safety of omadacycline in patients afflicted with non-tuberculous mycobacteria abscessus, or NTM abscessus, which are environmental organisms that can be found in soil, dust, and water, including natural and municipal water sources. Infection occurs when a person is exposed to NTM organisms. NTM abscessus can form difficult-to-eliminate biofilms, which are collections of microorganisms that stick to each other, and adhere to surfaces in moist environments. Although severe infection can affect the lymph nodes, skin, soft tissues, bones, and joints, the vast majority of NTM abscessus infection cases are pulmonary. The diagnosis of NTM abscessus infection is often delayed due to non-specific symptoms and a lack of disease state awareness by clinicians.
Other Data Generation
The company had 16 studies completed and 11 additional studies initiated or ongoing. The FDA has also approved two new antimicrobial susceptibility testing devices, including the first automated device, that included omadacycline. Collaborative research initiatives included the completion of year four of the company’s post-marketing required surveillance study and evaluation of the efficacy of NUZYRA in combination with other standard of care agents in a mouse model of pulmonary M. abscessus infection. The investigator-initiated research, or IIR, program included the completion of the first real-world use registry and initiation of two additional real-world studies. Data generation activities resulted in the publication of 24 manuscripts that address the use of NUZYRA in special pathogens, populations or disease states that the company expects will further define its therapeutic profile.
Sarecycline
Sarecycline, also known as SEYSARA in the U.S., is a novel, next generation, narrow spectrum tetracycline designed specifically for dermatological use. In July 2007, the company exclusively licensed the right to develop and commercialize sarecycline for the treatment of acne to Warner Chilcott Company, Inc. (which was acquired by Actavis PLC in October 2013 and became Allergan in October 2015) and, in September 2018, Allergan assigned such rights to Almirall. In February 2020, the company exclusively licensed to Almirall certain technology owned or in-licensed by it or its affiliates in order to research, develop and commercialize sarecycline for the treatment of acne in the People's Republic of China, Hong Kong, Macau and Taiwan, or the greater China region.
With respect to its technology as it relates to sarecycline, the company retains development and commercialization rights outside of the U.S. and the greater China region and, with respect to certain technology owned or in-licensed by Almirall or its affiliates necessary or useful to develop or commercialize sarecycline outside of the U.S. and the greater China region, the company exclusively licensed such technology from Almirall in February 2020, all of which is available for licensing to other partners in key international markets, such as the EU, Japan, the rest of Asia (excluding the greater China region), Canada and Latin America. In the event the company directly commercializes or sublicenses a third party to commercialize sarecycline outside of the U.S. and the greater China region, it owes Almirall a royalty on its or its affiliates’ net sales and a percentage of the consideration (e.g., milestones, royalties) it receives from its sublicensees in connection with their development and commercialization of sarecycline.
Almirall holds a nonexclusive license to develop and commercialize sarecycline for the treatment of rosacea in the U.S., and in the U.S., Paratek cannot grant rights on back-up compounds, lead candidate(s), or products licensed to Almirall for rosacea.
NUZYRA Commercialization Strategy
The company markets NUZYRA in the U.S. as an empiric monotherapy in the indications of ABSSSI and CABP for patients that have both a known or suspected resistant pathogen and at least one significant comorbidity,such as diabetes or renal impairment. The company retains worldwide commercial rights to omadacycline, with the exception in the People’s Republic of China, Hong Kong, Macau and Taiwan, where it has entered into a collaboration agreement with Zai. The company plans to pursue the continued global expansion of NUZYRA to select markets including Japan, South Korea and Europe, through collaboration or distribution arrangements focused on the rare disease indication of NTM.
Manufacturing
CIPAN
In November 2016, the company entered into a manufacturing and services agreement with CIPAN – Companhia Industrial Produtora de Antibióticos, or CIPAN, and subsequently amended and restated such manufacturing and services agreement in April 2018 to include, among other things, an investment by the Company in a new facility area to increase the manufacturing capacity for production of crude omadacycline. The agreement, as subsequently amended, provides the terms and conditions under which CIPAN will manufacture and supply to the company increased quantities of minocycline starting material and crude omadacycline, or the CIPAN Products, for purification into omadacycline and, subsequently, for use in its products that contain omadacycline tosylate as the active pharmaceutical ingredient.
The company’s agreement with CIPAN will remain in effect for an initial term, as extended, after which the agreement will continue, with respect to each CIPAN Product, for successive renewal terms unless either it or CIPAN have given written notice of termination within a certain period prior to the expiration of either the initial or then-current renewal term.
Carbogen
In July 2021, the company entered into a supply agreement with CARBOGEN AMCIS AG, or Carbogen. The agreement provides for the terms and conditions under which Carbogen will manufacture and supply to the company the active pharmaceutical ingredient for its omadacycline product in bulk quantities, or the Carbogen Product.
Almac
In December 2016, the company entered into a manufacturing and services agreement with Almac Pharma Services Limited, or Almac. The manufacturing agreement, as subsequently amended, provides for the terms and conditions under which Almac will manufacture, package and supply to the company omadacycline oral solid dosage tablets in bulk form, or the Almac Products. Under this manufacturing agreement, the company is required to use commercially reasonable efforts to timely provide Almac with the active pharmaceutical ingredient needed to manufacture the Almac Products and perform related services.
Patheon
In July 2017, the company entered into a master manufacturing services agreement and corresponding product agreement with Patheon UK Limited, or Patheon. The agreements, as subsequently amended, provide for the terms and conditions under which Patheon will manufacture, package and supply to the company omadacycline in injectable form, or the Patheon Products. Under these agreements, the company is required to deliver to Patheon the active pharmaceutical ingredient needed to manufacture the Patheon Products.
Research and Development
The company’s research and development expenses totaled $37.8 million in 2022.
Intellectual Property
As of December 31, 2022, the company’s patent portfolio of owned or exclusively licensed patents and applications included 38 issued U.S. patents, 17 pending U.S. patent applications and corresponding foreign national or regional counterpart patents or applications. The company expects that the patents and patent applications in this portfolio, if issued, and if the appropriate maintenance, renewal, annuity or other government fees are paid, would expire between 2023 and 2041, excluding any additional terms from patent term adjustments or patent term extensions under the Hatch-Waxman Amendments.
NUZYRA (omadacycline)
The patent portfolio for omadacycline is directed to cover compositions of matter, formulations, salts and polymorphs, manufacturing methods, methods of use, dosing regimens, and modes of administration. The patents and patent applications covering omadacycline include patents and patent applications owned by the company. The issued composition of matter patent in the U.S. (U.S. Patent No. 7,553,828), if the appropriate maintenance, renewal, annuity, or other governmental fees are paid, was expected to expire in 2023, however, the company’s additional term for certain omadacycline patents may result from the patent term extension provision of the Hatch-Waxman Amendments of 1984, including the composition of matter patent which is anticipated to be extended until May 2028 and a method of use patent (U.S. 9,265,740) is expected to be extended until October 2030. Filings for both patent term extensions have been made with the U.S. Patent & Trademark Office. On February 17, 2023, the U.S. Patent & Trademark Office granted an interim one-year extension of the U.S. Patent No. 7,553,828 while they continue to review its petition for patent term extension. Omadacycline has received Qualified Infectious Disease Product, or QIDP, designation under the Generating Antibiotic Incentives Now Act, or the GAIN Act. This may provide up to an additional five years of market exclusivity layered with protection provided by the Hatch-Waxman Amendments, which GAIN also enables exclusivity to 2028. The company expects that the other patents and patent applications in this portfolio, if issued, and if the appropriate maintenance, renewal, annuity or other governmental fees are paid, would expire between 2023 and 2041, excluding any additional terms from patent term adjustments or patent term extensions under the Hatch-Waxman Amendments.
SEYSARA (sarecycline)
The patent portfolio for the company’s acne and rosacea program is directed to cover compositions of matter, methods of use, methods of manufacturing, as well as salts and polymorphs of sarecycline. Amongst other patent filings and granted patents, the company’s patent portfolio includes issued U.S. Patent No. 8,318,706, or the ‘706 Patent, which covers composition of matter of sarecycline and issued U.S. Patent No. 8,513,223, or the ‘223 Patent, which covers methods of use for sarecycline, and corresponding foreign national or regional counterpart applications. The ‘706 Patent is expected to expire in 2032 (this expiry taking into account the expected patent term extension as provided by the Hatch-Waxman Amendments) and the ‘223 Patent is expected to expire in 2029, if the appropriate maintenance, renewal, annuity or other governmental fees are paid. Filing for the patent term extension has been made with the U.S. Patent & Trademark Office. In February 2020, the company finalized a license agreement with Almirall granting the company exclusive rights to certain technology owned or in-licensed by Almirall or its affiliates that is necessary or useful to develop or commercialize sarecycline outside of the U.S., including exclusive rights in joint intellectual property and certain Almirall solely owned intellectual property.
Intermezzo
As of December 31, 2022, the company’s patent portfolio of owned or exclusively licensed patents and applications includes four issued U.S. patents directed to formulations and methods of use. The issued U.S. patents expire between 2025 and 2029.
Trademarks
The company has registered trademarks and service marks or pending trademark and services mark applications in a number of countries for PARATEK, PARATEK & HEXAGON DESIGN, NUZYRA and its design logo, and other marks which it uses or may use in connection with its pharmaceutical research and development, as well as with its product candidates. SEYSARA is a trademark for which Almirall has registered in the U.S. and China and for which Paratek has applied for in a number of foreign countries.
Competition
NUZYRA competes with other antibiotics in the serious bacterial skin infection market. These include, but are not limited to, vancomycin, marketed as a generic by Abbott Laboratories and others; linezolid, marketed as Zyvox by Pfizer Inc. and available as a generic; tedizolid, marketed as Sivextro; daptomycin, marketed as Cubicin by Merck Pharmaceuticals, Inc. and available as a generic; dalbavancin, marketed as Dalvance by Abbvie; oritavancin, marketed as Orbactiv and delafloxacin, marketed as Baxdela by Melinta Therapeutics, Inc.; quinupristin/dalfopristin, marketed as Synercid by Pfizer, Inc.; tigecycline, marketed as Tygacil by Pfizer Inc. and available as a generic; telavancin, marketed as Vibativ by Cumberland Therapeutics Inc.; ceftaroline, marketed as Teflaro by Abbvie; and generic trimethoprim/sulfamethoxazole and clindamycin.
NUZYRA also competes with other antibiotics in the community-acquired pneumonia market. These include azithromycin, marketed as Zithromax and Z-PAK by Pfizer Inc. and available as a generic; clarithromycin, marketed as Biaxin by Abbott Laboratories and available as a generic; moxifloxacin, marketed as Avelox by Bayer AG and available as a generic; levofloxacin, marketed as Levaquin by Johnson & Johnson and available as a generic; tigecycline, marketed as Tygacil by Pfizer Inc. and available as a generic; linezolid, marketed as Zyvox by Pfizer Inc. and available as a generic; ceftriaxone, marketed as Rocephin by F. Hoffman-La Roche Ltd and available as a generic; ceftaroline, marketed as Teflaro by Abbvie; delafloxacin, marketed as Baxdela by Melinta Therapeutics Inc; and lefamulin, marketed as Xenleta by Nabriva Therapeutics. The company is also aware of various drugs that are or may eventually be under development for the treatment of CABP, including, but not limited to, GSK2140944, under development by GSK, and nemanoxacin, under development by TaiGen Biotechnology.
History
Paratek Pharmaceuticals, Inc. was founded in 1996.
