Methotrexate

Adalimumab-aaty will be priced at an 85% discount to HUMIRA® (adalimumab) Branded and unbranded versions of Celltrion USA's adalimumab biosimilar help provide more affordable options for patients JERSEY CITY, N.J., May 9, 2024 /PRNewswire/ -- Celltrion USA announced today that adalimumab-aaty, the company's high-concentration (100 mg/mL) and citrate-free formulation biosimilar to HUMIRA ® (adalimumab), is now available at a low wholesale acquisition cost (WAC). Adalimumab-aaty will be priced as WAC list price at an 85% discount to the current WAC list price of HUMIRA. Adalimumab-aaty is also available from Celltrion USA under the brand name YUFLYMA®, which launched in July 2023 and is available at a 5% discount to the current WAC list price of HUMIRA. Adalimumab-aaty is approved for the treatment of eight conditions, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa. "Access to medications in the U.S. has become increasingly complex, and there is so much value that biosimilars add with competition in the marketplace," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "The availability of branded and unbranded versions of adalimumab-aaty will improve the accessibility of adalimumab biosimilars in the U.S., providing economic benefits for patients and the overall healthcare system." Adalimumab-aaty is available as 40 mg/0.4mL, 80 mg/0.8mL and 20 mg/0.2mL. IMPORTANT SAFETY INFORMATION[1] This important safety information also applies to YUFLYMA® (adalimumab-aaty) SERIOUS INFECTIONS Patients treated with adalimumab-aaty are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue adalimumab-aaty if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before adalimumab-aaty use and during therapy. Initiate treatment for latent TB prior to adalimumab-aaty use. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. Carefully consider the risks and benefits of treatment with adalimumab-aaty prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with adalimumab-aaty, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Treatment with adalimumab-aaty should not be initiated in patients with an active infection, including localized infections. Patients over 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Discontinue adalimumab-aaty if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with adalimumab-aaty, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy. Drug interactions with biologic products: In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of adalimumab-aaty with abatacept or anakinra is not recommended in patients with RA. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of adalimumab-aaty and other biologic products for the treatment of RA, PsA, AS, CD, UC, PS, and HS. Concomitant administration of adalimumab-aaty with other biologic DMARDs (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions. A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including adalimumab products. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to the use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. Consider the risks and benefits of TNF blocker treatment including adalimumab-aaty prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC), or when considering continuing a TNF blocker in patients who develop a malignancy. In controlled portions of clinical trials of some adalimumab products, more cases of malignancies have been observed compared to control-treated adult patients. Non-melanoma skin cancer (NMSC) was reported during clinical trials for patients treated with adalimumab products. During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, PS and HS, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated patients and 0.2 (0.10, 0.59) per 100 patient-years among control-treated patients. Examine all patients, particularly those with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, for the presence of NMSC prior to and during treatment with adalimumab-aaty. In clinical trials of some adalimumab products, there was an approximately threefold higher rate of lymphoma than expected in the general U.S. population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to severalfold) than the general population for the development of lymphoma, even in the absence of TNF blockers. Postmarketing cases of acute and chronic leukemia were reported with the use of a TNF blocker in RA and other indications. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving adalimumab were lymphomas; other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. HYPERSENSITIVITY Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of adalimumab-aaty and institute appropriate therapy. HEPATITIS B VIRUS REACTIVATION Use of TNF blockers, including adalimumab-aaty, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy. Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV and closely monitor such patients for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, stop adalimumab-aaty and initiate effective antiviral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of adalimumab-aaty therapy in this situation and monitor patients closely. NEUROLOGIC REACTIONS Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Exercise caution in considering the use of adalimumab-aaty in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of adalimumab-aaty should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders. HEMATOLOGIC REACTIONS Rare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents. Adverse reactions of the hematologic system, including medically significant cytopenia, have been infrequently reported with adalimumab products. Consider discontinuation of adalimumab-aaty therapy in patients with confirmed significant hematologic abnormalities. HEART FAILURE Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products. Exercise caution when using adalimumab-aaty in patients who have heart failure and monitor them carefully. AUTOIMMUNITY Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab-aaty, discontinue treatment. IMMUNIZATIONS Patients on adalimumab-aaty may receive concurrent vaccinations, except for live vaccines. It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating adalimumab-aaty therapy. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab products. The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. ADVERSE REACTIONS The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. INDICATIONS Adalimumab-aaty is a tumor necrosis factor (TNF) blocker indicated for: Rheumatoid Arthritis (RA): reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA Juvenile Idiopathic Arthritis (JIA): reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older Psoriatic Arthritis (PsA): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsA Ankylosing Spondylitis (AS): reducing signs and symptoms in adult patients with active AS Crohn's Disease (CD): treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older Ulcerative Colitis (UC): treatment of moderately to severely active ulcerative colitis in adults Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers Plaque Psoriasis (Ps): treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate Hidradenitis Suppurativa (HS): treatment of adult patients with moderate to severe hidradenitis suppurativa Please see full Prescribing Information including Boxed Warning for adalimumab-aaty About a dalimumab-aaty [1] Adalimumab-aaty is an unbranded version of YUFLYMA® (CT-P17, biosimilar adalimumab). YUFLYMA is a recombinant fully human anti–tumour necrosis factor α (anti-TNFα) monoclonal antibody. YUFLYMA is FDA-approved for the treatment of patients with rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis and Hidradenitis Suppurativa. Following the launch of 40mg/0.4mL in July 2023 and 80mg/0.8mL in December 2023, additional dosage form of 20mg/0.2mL was launched in the U.S. in March 2024. About Celltrion USA Celltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion currently has five biosimilars approved by the U.S. FDA: INFLECTRA ® (infliximab-dyyb), TRUXIMA ® (rituximab-abbs), HERZUMA ® (trastuzumab-pkrb), VEGZELMA ® (bevacizumab-adcd) and YUFLYMA®(adalimumab-aaty) as well as a new biologic ZYMFENTRA™. Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit: FORWARD-LOOKING STATEMENT Certain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion that may constitute forward-looking statements, under pertinent securities laws. These statements may be identified by words such as "prepares," "hopes to," "upcoming," "plans to," "aims to," "to be launched," "is preparing," "once gained," "could," "with the aim of," "may," "once identified," "will," "working towards," "is due," "become available," "has potential to," the negative of these words or such other variations thereon or comparable terminology. In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion's management, of which many are beyond its control. Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions with respect to the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or results expressed or implied by such forward-looking statements. Such Risks and uncertainties may include, among other things, uncertainties regarding the launch timing and commercial success of Celltrion in the United States; the uncertainties inherent in supply chain, manufacturing, research and development, and the possibility of unfavorable new clinical data and further analyses of existing clinical data as it relates to Celltrion products; intellectual property and/or litigation/settlement implications; decisions by the FDA impacting labeling, manufacturing processes, safety, promotion, and/or other matters that could affect the availability or commercial potential of Celltrion products; and uncertainties regarding access challenges for our biosimilar products where our product may not receive appropriate formulary access or remains in a disadvantaged position relative to competitive products; and competitive developments. A further description of risks and uncertainties can be found in Celltrion's Annual Report. Although forward-looking statements contained in this presentation are based upon what management of Celltrion believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Celltrion undertakes no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. The reader is cautioned not to place undue reliance on forward-looking statements. Trademarks HUMIRA® is a registered trademark of AbbVie Biotechnology Ltd. YUFLYMA® is a registered trademark of Celltrion, Inc., used under license. References US-YUF-24-00007 04/24 Contacts Sarah Amundsen [email protected] +1 920-946-0918 SOURCE Celltrion USA

Clinical Results and Potential New Drug Application Submission Expected in the Second Half of 2024 LEXINGTON, Mass.--(BUSINESS WIRE)-- Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a biotechnology company devoted to discovering and developing innovative therapies designed to treat immune-mediated and metabolic diseases, today announced enrollment of the first patient in a Phase 3 dry eye chamber clinical trial designed to enable a potential resubmission of the New Drug Application (NDA) of topical ocular 0.25% reproxalap, an investigational RASP modulator, for the treatment of dry eye disease. Contingent on positive results from the clinical trial, Aldeyra expects to resubmit the NDA of reproxalap for the treatment of dry eye disease to the U.S. Food and Drug Administration (FDA) in the second half of 2024. Aldeyra intends to include in the potential NDA resubmission a draft label describing chronic and acute improvement in symptoms and ocular redness. To Aldeyra’s knowledge, the draft label could represent the first dry eye disease label that incorporates clinical data assessed acutely in a dry eye chamber, and potentially the first dry eye disease label that includes reduction in ocular redness for a chronically administered drug. Per FDA guidance, the planned review period for the potential NDA resubmission is expected to be six months. In the clinical trial, patients are administered vehicle (the drug product without the active ingredient) before and during exposure to a dry eye chamber. Qualifying patients are subsequently randomized to receive either reproxalap or vehicle before and during exposure to an additional dry eye chamber. Approximately 110 patients are expected to be enrolled to assess the primary endpoint of ocular discomfort. In four previously completed dry eye chamber clinical trials of reproxalap, when analyzed in aggregate with the trial design and statistical plan recently discussed with the FDA, ocular discomfort in the dry eye chamber following treatment with reproxalap was statistically lower than that of vehicle (p=0.0003). A clinical trial at a different dry eye chamber, in addition to a traditional six-week field clinical trial, are expected to be conducted in parallel as part of a comprehensive strategy designed to account for disease heterogeneity and potential differences in clinical sites and environment. Consistent with previously disclosed guidance and based on the current operating plan, cash, cash equivalents, and marketable securities of $133.0 million as of March 31, 2024 are projected to be sufficient to fund operations to beyond the end of 2026. About Aldeyra Aldeyra Therapeutics is a biotechnology company devoted to discovering innovative therapies designed to treat immune-mediated and metabolic diseases. Our approach is to develop pharmaceuticals that modulate protein systems, instead of directly inhibiting or activating single protein targets, with the goal of optimizing multiple pathways at once while minimizing toxicity. Our product candidates include RASP (reactive aldehyde species) modulators ADX-629, ADX-246, ADX-248, and chemically related molecules for the potential treatment of immune-mediated and metabolic diseases. Our late-stage product candidates are reproxalap, a RASP modulator for the potential treatment of dry eye disease and allergic conjunctivitis, and ADX-2191, a novel formulation of intravitreal methotrexate for the potential treatment of retinitis pigmentosa. Safe Harbor Statement This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Aldeyra’s future expectations, plans, and prospects, including without limitation statements regarding: the goals, opportunity, and potential for reproxalap; the outcome and expected timing and the results of Aldeyra’s planned clinical trials, including planned and ongoing clinical trials for reproxalap; the outcome and timing of the FDA’s review, acceptance and/or approval of a NDA resubmission for reproxalap and the adequacy of the data included in the original NDA and the potential NDA resubmission; Aldeyra’s expectations regarding the labeling of reproxalap, if approved; and Aldeyra’s projected cash runway. Aldeyra intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terms such as, but not limited to, “may,” “might,” “will,” “objective,” “intend,” “should,” "could," “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “on track,” “scheduled,” “target,” “design,” “estimate,” “predict,” “contemplates,” “likely,” “potential,” “continue,” “ongoing,” “aim,” “plan,” or the negative of these terms, and similar expressions intended to identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions, and uncertainties. Aldeyra is at an early stage of development and may not ever have any products that generate significant revenue. All of Aldeyra's development timelines may be subject to adjustment depending on recruitment rate, regulatory review, preclinical and clinical results, funding, and other factors that could delay the initiation, enrollment, or completion of clinical trials. Important factors that could cause actual results to differ materially from those reflected in Aldeyra's forward-looking statements include, among others, the timing of enrollment, commencement and completion of Aldeyra's clinical trials, the timing and success of preclinical studies and clinical trials conducted by Aldeyra and its development partners; delay in or failure to obtain regulatory approval of Aldeyra's product candidates, including as a result of the FDA not accepting Aldeyra’s regulatory filings, issuing a complete response letter, or requiring additional clinical trials or data prior to review or approval of such filings or in connection with resubmissions of such filings; the ability to maintain regulatory approval of Aldeyra's product candidates, and the labeling for any approved products; the risk that prior results, such as signals of safety, activity, or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or clinical trials involving Aldeyra's product candidates in clinical trials focused on the same or different indications; the scope, progress, expansion, and costs of developing and commercializing Aldeyra's product candidates; uncertainty as to Aldeyra’s ability to commercialize (alone or with others) and obtain reimbursement for Aldeyra's product candidates following regulatory approval, if any; the size and growth of the potential markets and pricing for Aldeyra's product candidates and the ability to serve those markets; Aldeyra's expectations regarding Aldeyra's expenses and future revenue, the timing of future revenue, the sufficiency or use of Aldeyra's cash resources and needs for additional financing; the rate and degree of market acceptance of any of Aldeyra's product candidates; Aldeyra's expectations regarding competition; Aldeyra's anticipated growth strategies; Aldeyra's ability to attract or retain key personnel; Aldeyra’s commercialization, marketing and manufacturing capabilities and strategy; Aldeyra's ability to establish and maintain development partnerships; Aldeyra’s ability to successfully integrate acquisitions into its business; Aldeyra's expectations regarding federal, state, and foreign regulatory requirements; political, economic, legal, social, and health risks, public health measures, and war or other military actions, that may affect Aldeyra’s business or the global economy; regulatory developments in the United States and foreign countries; Aldeyra's ability to obtain and maintain intellectual property protection for its product candidates; the anticipated trends and challenges in Aldeyra's business and the market in which it operates; and other factors that are described in the “Risk Factors” and “Management's Discussion and Analysis of Financial Condition and Results of Operations” sections of Aldeyra's Annual Report on Form 10-K for the year ended December 31, 2023, and Aldeyra’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, which are on the Securities and Exchange Commission (SEC) and available on the SEC's website at . In addition to the risks described above and in Aldeyra's other filings with the SEC, other unknown or unpredictable factors also could affect Aldeyra's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and Aldeyra undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law. View source version on businesswire.com: Contacts Investors & Media: David Burke Tel: (917) 618-2651 investorrelations@aldeyra.com Source: Aldeyra Therapeutics, Inc. View this news release online at: