Tetracycline Hydrochloride

Novel Trial to Study the Reduction of Certain Pathogens Following Scaling and Root Planing Procedure LAVAL, Quebec, May 18, 2023 – Bausch Health Companies Inc. (NYSE/TSX: BHC) and its oral health care business, OraPharma, today announced the publication of a new study, which showed that ARESTIN® (minocycline HCI) microspheres, 1mg decreased certain pathogenic burdens, also known as infection burdens, in adults with periodontitis when applied immediately after scaling and root planning (SRP) and again at a three-month reapplication, versus SRP alone. ARESTIN is an FDA-approved antibiotic applied locally to gum pockets in adults with periodontitis following an SRP procedure and is used as part of an overall oral health program. ARESTIN should not be used in people who are allergic to minocycline or tetracyclines. The investigator-initiated trial, sponsored in part by Bausch Health, and conducted by researchers from the University of Minnesota School of Dentistry, appeared today in the Journal of Periodontology. The study showed minocycline application immediately after initial SRP and reapplication at 3-months after SRP decreased certain key pathogens and may have contributed to improvements in probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP) and gingival index (GI) compared to SRP alone. “Dental practices need to think about periodontal disease and the role of keystone pathogens that originate in the mouth, can travel, and may be associated with other systemic outcomes such as diabetes and cardiovascular disease,” said Richard Nagelberg, DDS, Director of Medical Affairs at Bausch Health. “This study represents an important path forward in helping to manage periodontal disease and we hope it encourages further research in the area of periodontal disease progression and how it may relate to the oral-systemic connection.” Since the pivotal trial, there was a gap in the literature on whether minocycline HCI microspheres, 1mg reduced specific periodontal pathogens. This study identified that the administration of minocycline HCI microspheres, 1mg did significantly decrease specific periodontal pathogens. The objective of the study entitled, Effect of Scaling and Root Planing With and Without Minocycline HCl Microspheres on Periodontal Pathogens and Clinical Outcomes: A Randomized Clinical Trial, was to determine if minocycline HCl plus SRP contributed to the improvement of certain clinical measures commonly seen in patients with gum disease. A secondary endpoint was to determine if minocycline microspheres HCl with SRP lowered specific pathogens responsible for periodontitis compared to SRP alone. Saliva and clinical outcomes were collected for both groups at baseline before SRP, 1-month reevaluation, and at 3 and 6-month periodontal recall. Minocycline microspheres (MM) were delivered to pockets ≥5 mm immediately after SRP and immediately after the 3-month periodontal maintenance. This study reported that of the 11 pathogens that play an instrumental role in periodontitis, there were six periodontal pathogens that had a statistically significant decrease at 1-month and four periodontal pathogens with a statistically significant decrease at the 6-month periodontal maintenance versus the SRP group alone. This study also reported that minocycline HCI plus SRP achieved greater improvement for probing depth, bleeding on probing, gingival index, and improvement in clinical attachment loss by the six-month periodontal maintenance versus SRP alone. Limitations of the study include the lack of a blinded examiner for clinical outcomes and lack of patient-reported outcome measures. The principal investigator (PI) collected saliva, recorded clinical measures and provided treatment for both groups. The participants in this study were predominantly from the Midwestern region, Caucasian and over the age of 50 years old, which does not represent the general population of individuals with periodontitis. “There was a larger decrease of Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum/periodonticum, Prevotella intermedia, Parvimonas micra and Eikenella corrodens in the SRP + MM group,” said Dr. Nagelberg. It is notable that minocycline HCl microspheres, 1mg immediately following SRP procedures reduced these specific periodontal pathogens by the 1-month reevaluation. The previous pivotal study (Williams et al., 2001) was conducted to determine if minocycline HCI plus SRP reduced pocket depth in patients with generalized moderate to advanced adult periodontitis versus SRP alone. Subjects treated with minocycline HCI plus SRP were found to have statistically significantly reduced probing pocket depth compared with those treated with SRP alone or SRP + vehicle at 9 months after initial treatment. About the Study A total of 70 participants were randomized to receive SRP alone, or SRP with minocycline HCl microspheres, 1mg following the procedure, and again at the 3-month periodontal visit. Participants in both groups received periodontal evaluations at baseline, one month, three months and six months following the initial SRP procedure. The primary goal of this study was to determine the adjunctive effects of minocycline microspheres (MM) on clinical outcomes of PD, CAL, BOP, and GI after SRP+MM compared to SRP alone. Secondary outcome variables were the relative numbers of 11 periodontal pathogens in saliva after SRP+MM compared to SRP alone. The bacterial load and pathogenic burden were determined using a salivary test. Microorganisms and secondary periodontal measurements were compared between groups using generalized linear mixed-effects models, with fixed effects for group, visit, site (for clinical measurements), and group-by-visit and group-by-site interactions, and random effects for participant and site within participant. Mean changes from baseline were compared between groups via group-by-visit interaction tests. The six periodontal pathogens observed in the test group to have a statistically significant decrease compared to the SRP alone group at the one-month follow-up visit were Tannerella forsythia (Tf) (0.003), Treponema denticola(Td) (0.01), Fusobacterium nucleatum/periodonticum (Fn/Fp)(0.0009), Prevotella intermedia (Pi) (0.04), Parvimonas micra (Pm) (<0.0001), andEikenella corrodens (Ec) (0.02). Further, the four periodontal pathogens observed in the test group to have a statistically significant decrease compared to the SRP alone group at the final six-month visit were Fusobacterium nucleatum/periodonticum (Fn/Fp) (0.02), Prevotella intermedia (0.05), Campylobacter rectus (Cr) (0.04) and Eikenella corrodens (0.0002). Limitations of the study include the lack of a blinded examiner for clinical outcomes and lack of patient-reported outcome measures. The principal investigator (collected saliva, recorded clinical measures and provided treatment for both groups. The participants in this study were predominantly from the Midwestern region, Caucasian and over the age of 50 years old, which does not represent the general population of individuals with periodontitis. The statistical analysis for this research was supported by a grant from the National Institutes of Health’s National Center for Advancing Translational Science. Important Safety Information for ARESTIN® INDICATION ARESTIN® (minocycline HCl) Microspheres, 1mg is indicated as an adjunct to scaling and root planing (SRP) procedures for reduction of pocket depth in patients with adult periodontitis. ARESTIN may be used as part of a periodontal maintenance program, which includes good oral hygiene and SRP. IMPORTANT SAFETY INFORMATION ARESTIN is contraindicated in any patient who has a known sensitivity to minocycline or tetracyclines. Hypersensitivity reactions and hypersensitivity syndrome that included, but were not limited to anaphylaxis, anaphylactoid reaction, angioneurotic edema, urticaria, rash, eosinophilia, and one or more of the following: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis may be present. Swelling of the face, pruritus, fever and lymphadenopathy have been reported with the use of ARESTIN. Some of these reactions were serious. Post-marketing cases of anaphylaxis and serious skin reactions such as Stevens Johnson syndrome and erythema multiforme have been reported with oral minocycline, as well as acute photosensitivity reactions. THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH, AND THEREFORE SHOULD NOT BE USED IN CHILDREN OR IN PREGNANT OR NURSING WOMEN. Tetracyclines, including oral minocycline, have been associated with development of autoimmune syndromes including a lupus-like syndrome manifested by arthralgia, myalgia, rash, and swelling. Sporadic cases of serum sickness-like reaction have presented shortly after oral minocycline use, manifested by fever, rash, arthralgia, lymphadenopathy and malaise. In symptomatic patients, diagnostic tests should be performed and ARESTIN treatment discontinued. The use of ARESTIN in an acutely abscessed periodontal pocket or for use in the regeneration of alveolar bone has not been studied. The safety and effectiveness of ARESTIN has not been established in immunocompromised patients or in those with coexistent oral candidiasis. Use with caution if there is a predisposition to oral candidiasis. In clinical trials, the most frequently reported nondental treatment-emergent adverse events were headache, infection, flu syndrome, and pain. To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Click here for full Prescribing Information. About ARESTIN ARESTIN® is an FDA-approved antibiotic applied locally to gum pockets in adults with periodontitis following an SRP procedure and is used as part of an overall oral health program. ARESTIN should not be used in people who are allergic to minocycline or tetracyclines. In 2001, a pivotal study was conducted to: 1) determine whether the administration of minocycline microspheres would enhance the therapeutic effect of scaling and root planing in patients with chronic periodontitis, and 2) determine whether the compound was safe and well tolerated. Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in an investigator-blind, multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. About Periodontitis Risks According to the National Health and Nutrition Examination Survey (NHANES), 42.2% of United States adults have periodontitis. There are certain factors that increase the risk for developing gum disease which include smoking, diabetes, poor oral hygiene, obesity and diabetes. In addition, gum disease may provide a gateway for bacteria to enter the body and trigger systemic health issues and inflammation in the body, though further research is necessary. About OraPharma OraPharma is a specialty pharmaceutical company committed to partnering with dental professionals to improve oral health. Founded more than 25 years ago, OraPharma includes a curated portfolio of treatments for periodontal disease and multiple regenerative solutions for oral surgery. More information can be found at https://www.orapharma.com/. About Bausch Health Bausch Health Companies Inc. (NYSE/TSX: BHC) is a global diversified pharmaceutical company whose mission is to improve people’s lives with our health care products. We develop, manufacture and market a range of products primarily in gastroenterology, hepatology, neurology, dermatology, international pharmaceuticals and eye health, through our controlling interest in Bausch + Lomb. With our leading durable brands, we are delivering on our commitments as we build an innovative company dedicated to advancing global health. For more information, visit www.bauschhealth.com and connect with us on Twitter and LinkedIn. ###

-- NUZYRA® (omadacycline) Generated Net U.S. Sales of $26.2 Million from the Core Commercial Business, a 32% Increase Over First Quarter 2022 -- Company Reiterates Full-Year Revenue Guidance of $143 to $158 Million -- Announces Full-Year R&D and SG&A Expense Guidance of $160 to $170 Million, Approximately $20 Million in Savings Over Annualized Fourth Quarter 2022 Spend Rate1, Enabled by Operational Efficiencies BOSTON, May 09, 2023 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals, Inc. (Nasdaq: PRTK), a commercial-stage biopharmaceutical company focused 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, today reported financial results and provided an update on corporate activities for the first quarter ended March 31, 2023. “The continued and robust year-over-year growth in our NUZYRA core commercial revenue combined with the sales momentum seen in the latter half of the first quarter, which has continued through April, supporting our confidence in our commercial strategy,” said Evan Loh, M.D., chief executive officer at Paratek. “The strong demand we have seen in our commercial business to date, along with the progress we are making in our BARDA contract, allows us to reiterate 2023 revenue guidance of $143 to $158 million. Consistent with our commitment to accelerate our pathway to profitability, 2023 R&D and SG&A expense guidance is $160 to $170 million, which represents a significant reduction from our annualized fourth quarter 2022 spend rate1 that will be achieved through operational efficiencies.” _______________1 R&D and SG&A expense in the fourth quarter of 2022 was $68.1 million, which included a contingent non-recurring charge of $21.9 million. Excluding this charge, R&D and SG&A expense in the fourth quarter of 2022 was $46.2 million, which incorporated the full cost burden of the community sales expansion completed in the second half of 2022. Recent Highlights Non-Tuberculous Mycobacteria (NTM) Rare Disease Program: Real World Evidence Presentation: In a poster presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in April 2023 entitled, “A Multicenter Evaluation of Treatment Durability and Safety of Omadacycline for Mycobacterium abscessus Infections,” omadacycline demonstrated a high degree of clinical durability and safety at three, six, and 12 months in 63 patients with NTM infections.Ex-US Outlicensing Opportunities: Following the receipt of formal guidance on a NTM registration program in Japan during the first quarter, the company has initiated regulatory activities in Europe focused on establishing orphan disease designation and a development pathway for approval of NUZYRA for NTM caused by Mycobacterium abscessus. Progress on partnerships focused on the development and commercialization of NUZYRA for NTM in both Japan and Europe continues. The company anticipates a formal partnership in Japan to be announced in the second half of 2023.Development Program: Enrollment continues in an ongoing Phase 2b study designed to explore the potential utility of omadacycline as a treatment for NTM pulmonary infections due to Mycobacterium abscessus. The company anticipates that enrollment will be complete by the end of 2023. First Quarter 2023 Financial Results Total revenue for the first quarter of 2023 was $31.2 million compared to $24.9 million for the same period in the prior year. Total revenue for the first quarter of 2023 was comprised of the following: NUZYRA net U.S. sales of $26.2 million, which represented a 32% increase from $19.9 million for the same period in the prior year.Government contract service and grant revenue earned from cost reimbursement under the BARDA contract of $3.8 million, a 12% decrease from $4.3 million for the same period in the prior year.Collaboration and royalty revenue of $1.2 million, a 71% increase from $0.7 million for the same period in the prior year, which primarily represents royalty revenues earned on sales of NUZYRA in China and on sales of SEYSARA® (sarecycline) in the United States. Research and development (R&D) expenses were $7.3 million for the first quarter of 2023, compared to $7.5 million for the same period in the prior year. Selling, general and administrative (SG&A) expenses were $33.5 million for the first quarter of 2023, compared to $27.6 million for the same period in the year. The increase in SG&A expenses is primarily the result of costs incurred in connection with the NUZYRA community expansion. Paratek reported a net loss of $20.1 million, or $(0.35) per share, for the first quarter of 2023, compared to a net loss of $17.9 million, or $(0.35) per share, for the same period in the prior year. Paratek had cash and cash equivalents of $45.0 million as of March 31, 2023. Based upon the Company’s current operating plan, this balance of cash and cash equivalents may not be sufficient to fund operations through the first quarter of 2024. The Company expects to address future cash needs, including the maturity of its outstanding convertible senior subordinated notes due May 2024, primarily through a combination of product sales, royalties, public or private equity offerings, debt or other structured financings, strategic partnership opportunities, government procurements and active management of cash and expenses through operational efficiencies. If these activities are successful, the Company expects to be able to fund operations beyond the first quarter of 2024. 2023 Financial Guidance Paratek reiterated its full-year 2023 revenue guidance announced earlier this year, which is expected to be in the range of $143 to $158 million, which includes the following components: NUZYRA net U.S. sales of approximately $125 to $135 million.BARDA government contract service and grant revenue between $15 to $20 million.Royalty and collaboration revenue of approximately $3 million. Paratek also announced its full-year 2023 R&D and SG&A expense guidance, which is expected to be in the range of $160 to $170 million, and include the following components: Core business R&D and SG&A expenses of $145 to $150 million.Reimbursable BARDA R&D and U.S. onshoring expenses of $15 to $20 million. Call and Webcast Paratek’s earnings conference call for the quarter ended March 31, 2023, will be broadcast at 4:30 p.m. EST on May 9, 2023. The live audio webcast can be accessed under “Events and Presentations” in the Investor Relations section of Paratek’s website at www.ParatekPharma.com Domestic investors wishing to participate in the call should dial: 1-800-920-3371 and international investors should dial: 1-212-231-2909. The conference ID is 22026760. Investors can also access the call at: https://viavid.webcasts.com/starthere.jsp?ei=1611304&tp_key=5fe62a51b9 Website Information Paratek routinely posts important information for investors on the Investor Relations section of its website at www.ParatekPharma.com. Paratek intends to use this website as a means of disclosing material, non-public information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investor Relations section of Paratek’s website, in addition to following its press releases, U.S. Securities and Exchange Commission (SEC) filings, public conference calls, presentations and webcasts. The information contained on, or that may be accessed through, Paratek’s website is not incorporated by reference into, and is not a part of, this document. About Paratek Pharmaceuticals, Inc. Paratek Pharmaceuticals, Inc. is a commercial-stage biopharmaceutical company focused 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 lead commercial product, NUZYRA® (omadacycline), is a once-daily oral and intravenous antibiotic available in the United States for the treatment of adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). Paratek has a collaboration agreement with Zai Lab for the development and commercialization of omadacycline in the greater China region and retains all remaining global rights. Paratek is also conducting a Phase 2b study with NUZYRA in a rare disease, nontuberculous mycobacterial (NTM) pulmonary disease, caused by Mycobacterium abscessus complex. Paratek estimates this opportunity represents a potential $1 billion addressable market in the United States. Paratek exclusively licensed U.S. rights and rights to the greater China territory for SEYSARA® (sarecycline), a once-daily oral therapy for the treatment of moderate to severe acne vulgaris, to Almirall, LLC. Paratek retains the development and commercialization rights for sarecycline in the rest of the world. In 2019, Paratek was awarded a contract from the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), now valued at up to $304 million, to support the development and U.S.-based manufacturing of NUZYRA for pulmonary anthrax. For more information, visit www.ParatekPharma.com or follow us on LinkedIn and Twitter. About NUZYRA® NUZYRA® (omadacycline) is a novel antibiotic with both once-daily oral and intravenous (IV) formulations for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). A modernized tetracycline, NUZYRA is specifically designed to overcome tetracycline resistance and exhibits activity across a spectrum of bacteria, including Gram-positive, Gram-negative, atypicals and other drug-resistant strains. Forward Looking Statements This press release contains forward-looking statements including statements related to our overall strategy, products, prospects, potential and expected results, including statements about our expectations regarding the Company's future growth and performance, revenue and operating expense projections, our ability to continue to execute and deliver on our BARDA contract, the status of our Phase 2b NTM abscessus study, the potential market opportunity for NTM in the United States, Japan and Europe, the potential for a partnership in Japan and Europe for the development and commercialization of NUZYRA for NTM, and our anticipated cash runway. All statements, other than statements of historical facts, included in this press release are forward-looking statements, and are identified by words such as “expect,” “anticipate,” “continue,” “will” and other words and terms of similar meaning. These forward-looking statements are based upon our current expectations and involve substantial risks and uncertainties. We may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in our forward-looking statements and you should not place undue reliance on these forward-looking statements. Our actual results and the timing of events could differ materially from those included in such forward-looking statements as a result of these risks and uncertainties. These and other risk factors are discussed under "Risk Factors" and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2022 and our other filings with the Securities and Exchange Commission. We expressly disclaim any obligation or undertaking to update or revise any forward-looking statements contained herein. PARATEK PHARMACEUTICALS, INC. Condensed Consolidated Balance Sheets(unaudited)(in thousands) As of March 31, December 31, 2023 2022 Cash, cash equivalents and marketable securities$45,026 $34,248 Total assets 150,828 172,538 Working capital 78,269 99,454 Total current liabilities 32,745 37,388 Long-term debt 257,695 256,946 Common stock and additional paid-in capital 761,554 759,407 Accumulated deficit (950,592) (930,449)Total stockholders' deficit (189,038) (171,042) Condensed Consolidated Statement of Operations(unaudited)(in thousands, except loss per share data) Three Months EndedMarch 31, 2023 2022 Product revenue, net$26,213 $19,918 Government contract service revenue 1,806 2,172 Government contract grant revenue 2,028 2,099 Collaboration and royalty revenue 1,189 672 Net revenue$31,236 $24,861 Expenses: Cost of product revenue 6,244 3,494 Research and development 7,308 7,478 Selling, general and administrative 33,489 27,602 Total operating expenses 47,041 38,574 Loss from operations (15,805) (13,713)Other income and expenses: Interest income 221 107 Interest expense (4,476) (4,479)Other (losses) gains, net (22) 175 Net loss before provision for income taxes$(20,082) $(17,910)Provision for income taxes (61) — Net loss (20,143) (17,910)Other comprehensive (loss) Unrealized (loss) on available-for-sale securities, net of tax — (171)Comprehensive loss$(20,143) $(18,081)Basic and diluted net loss per common share$(0.35) $(0.35)Weighted average common stock outstanding Basic 56,903,420 52,149,538 Diluted 56,903,420 52,149,538 CONTACT: Investor Relations:Hans VitzthumLifeSci Advisorsir@ParatekPharma.comPhone: 617-430-7578 Media:Christine FanelleScient PRChristine@scientpr.comPhone: 215-595-5211