The study of the effectiveness of anti-TNF antibody maintenance treatment combined with elemental diet for Crohn's disease patients - The study of the effectiveness of anti-TNF antibody maintenance treatment combined with elemental diet for Crohn's disease patients

Start Date01 Feb 2012

Sponsor / Collaborator-

NCT01240876 / CompletedPhase 1/2

A Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Study to Evaluate the Safety and Efficacy of CEP-37247 Administered at Single Doses of 0.5, 1, 3, 6, or 12 mg by the Transforaminal Epidural Route for the Treatment of Patients With Lumbosacral Radicular Pain Associated With Disk Herniation

The primary objective of the study is to evaluate the safety and efficacy of CEP-37247 compared with placebo as assessed by the occurrence of adverse events, and the mean change in average pain intensity (API) in the affected leg.

Start Date01 Jan 2011

Sponsor / Collaborator

Cephalon, Inc.

EUCTR2009-014824-40-CZ / Not yet recruitingNot Applicable

An open label follow on study to evaluate the long-term safety, tolerability and efficacy of ART621 following fortnightly administration for 48 weeks in patients with rheumatoid arthritis concomitantly taking methotrexate.

Start Date03 Nov 2009

Sponsor / Collaborator

Arana Therapeutics Ltd.

100 Clinical Results associated with Placulumab

100 Translational Medicine associated with Placulumab

100 Patents (Medical) associated with Placulumab

1,009

Literatures (Medical) associated with Placulumab

01 Feb 2024·Zeitschrift fur Gastroenterologie

Symptoms and Management of Aseptic Liver Abscesses

Article

Author: Hafner, Susanne ; Kleger, Alexander ; Müller, Martin ; Seufferlein, Thomas

ABSTRACT:

Aseptic liver abscesses occur very rarely. Clinical guidelines on the management of the disease do not exist, and the diagnosis is challenging.We screen MEDLINE and PUBMED databases for relevant case reports from inception to November 2022. Information on patient age, sex, initial symptoms, the extent of abscess formation, further diagnoses, treatment, and course of the disease is analyzed.Thirty cases with sterile hepatic abscess formation are identified. In most patients (n=18), the spleen is affected as well. Patients typically present with fever, abdominal pain, and increased inflammatory values. Comorbidity with inflammatory bowel disease is very common (n=18) and is associated with a significantly younger age at the time of hepatic abscess development. In addition, many patients show autoimmune-mediated cutaneous, ocular, or arthritic rheumatoid manifestations. Histological examination of abscess material reveals neutrophilic infiltration. The majority of patients initially receive corticosteroid therapy. Furthermore, response to azathioprine, anti-TNF-α antibodies, and other immunomodulatory drugs is reported. Ten out of fourteen patients with a long-term follow-up (≥ 36 months) have at least one relapse of hepatic abscess formation.Aseptic hepatic abscesses should be considered in the case of sterile punctures and non-response to antibiotics. Patients with aseptic liver abscesses have a high risk of recurrence warranting immunomodulatory maintenance therapy.

01 Jan 2024·Disease-a-month : DM

Gastrointestinal Behçet's disease: Manifestations, diagnosis, and management

Review

Author: Butt, Edward ; Parupudi, Sreeram ; Manuelyan, Zara

Behçet's disease (BD) is a rare, inflammatory vascular disorder with recurrent oral and genital aphthous ulcers, along with ocular and cutaneous manifestations. Gastrointestinal (GI) BD may involve any portion of the GI tract. However, it is commonly described in the terminal ileum, followed by the ileocecal region. Diagnosis is challenging given lack of pathognomonic tests; therefore, it is based on clinical criteria. Management of intestinal BD includes different classes of medications including corticosteroids, 5-aminosalicylic acid, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody agents. In this review, we aim to focus on intestinal BD and provide details of clinical manifestations, diagnosis and therapeutic options of intestinal BD from gastroenterology viewpoint.

01 Jan 2024·Journal of gastroenterology and hepatology

Immunomodulators after the discontinuation of anti‐tumor necrosis factor‐alpha antibody treatment and relapse in ulcerative colitis: A multicenter cohort study

Article

Author: Andoh, Akira ; Asonuma, Kunio ; Munetomo, Yoshinori ; Okabayashi, Shinji ; Arimitsu, Shoko ; Matsubayashi, Mao ; Okano, Soh ; Yokoyama, Yoko ; Kiyohara, Hiroki ; Ichinari, Naoki ; Yamada, Masahiro ; Yamazaki, Hajime ; Umeno, Junji ; Nishimata, Nobuaki ; Ozaki, Ryo ; Kobayashi, Taku ; Shinzaki, Shinichiro ; Ozeki, Keiji

Abstract:

Background and Aim:

Strategies to reduce relapse using immunomodulators (IMs) after discontinuing anti‐tumor necrosis factor‐alpha (TNF‐α) antibody treatment are controversial in patients with ulcerative colitis (UC). In this study, we assessed the association between IMs after discontinuing anti‐TNF‐α antibody treatment and relapse in patients with UC.

Methods:

This retrospective, multicenter cohort study included 257 patients with UC in clinical remission. These patients discontinued anti‐TNF‐α antibody treatment between June 2010 and March 2019 and were followed up until March 2020. We evaluated the differences in relapse rates between patients with IMs (IM group) and those without IMs (non‐IM group) after discontinuing the treatment. Relapse was defined as further undergoing an induction treatment or colectomy. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for relapse. Exploratory analyses were performed to identify other factors that could predict relapse.

Results:

During the median follow‐up period of 22 months (interquartile range: 10–41), 114 relapses occurred: 42/100 (42.0%) in the IM group and 72/157 (45.9%) in the non‐IM group. In the multivariable analysis, IMs were not associated with relapse (HR, 0.95 [95% CI, 0.64–1.41]). In the exploratory analyses, discontinuation due to side effects (HR, 1.83 [95% CI, 1.18–2.82]) and younger age (HR, 0.99 [95% CI, 0.98–1.00]) predicted relapse.

Conclusion:

Immunomodulators were not associated with relapse after discontinuing anti‐TNF‐α antibody treatment in patients with UC. Careful patient follow‐up is needed when discontinuing due to side effects or when the patient is of a younger age at the time of discontinuation.

News (Medical) associated with Placulumab

09 May 2024

·www.prnewswire.com

Celltrion USA's adalimumab-aaty biosimilar to HUMIRA® now available at low wholesale acquisition cost

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

Drug ApprovalClinical ResultAcquisitionVaccine

07 Nov 2023

·www.globenewswire.com

Monte Rosa Therapeutics Presents Preclinical Data at ACR Convergence 2023 Demonstrating Potential of MRT-6160, a VAV1-targeted Molecular Glue Degrader, to Treat Immunological and Inflammatory Diseases

Data presented support broad potential therapeutic applications of MRT-6160 in a variety of autoimmune and inflammatory disorders driven by underlying dysregulation of T- and B-cells, including rheumatoid arthritis Investigational New Drug filing for MRT-6160 expected in 1H 2024 Data will be presented during Poster Session A on Sunday, November 12, 2023 from 9:00-11:00 am PT BOSTON, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced the company will present preclinical data at the American College of Rheumatology (ACR) Convergence Annual Meeting held November 10-15 in San Diego, CA. The data demonstrate that MRT-6160, a novel, highly selective MGD targeting VAV1, attenuated disease progression in a murine collagen-induced arthritis (CIA) model. In vitro, MRT-6160 induced selective degradation of VAV1, and attenuated TCR- and BCR-mediated activation and function of primary human T- and B-cells. In the CIA model, oral dosing of MRT-6160 elicited rapid VAV1 degradation across multiple tissues in a dose-dependent manner. Over the course of 20 days, MRT-6160 significantly decreased disease progression and endpoint functional scores compared to vehicle and showed a trend towards superior activity compared to an anti-TNF antibody. “We are highly encouraged by these preclinical data, which we believe further establish the importance of VAV1 as a potential therapeutic target in T- and B-cell mediated autoimmunity, as well as MRT-6160’s potential to broadly treat autoimmune and inflammatory diseases including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, psoriasis and other autoimmune diseases,” said Owen Wallace, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics. “Together with extensive preclinical data in other models of autoimmunity, these promising results further support MRT-6160 as it advances to the clinic, and we look forward to our anticipated IND filing in the first half of next year.” Poster presentation details: Poster Presentation: A VAV1-Directed Molecular Glue Degrader, MRT-6160, Reduces Joint Inflammation in the Collagen-Induced Arthritis Autoimmune Disease Model (abstract #0082)Session: Poster Session A: T Cell Biology & Targets in Autoimmune & Inflammatory DiseaseDate: Sunday, November 12, 2023 Time: 9:00-11:00 am PTPresenter: Marisa Peluso, Director, Target and Discovery BiologyLocation: Poster Hall About VAV1 and MRT-6160VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T-and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple indications, such as multiple sclerosis, rheumatoid arthritis, and dermatological disorders. MRT-6160 is a potent, highly selective, and orally bioavailable degrader of VAV1, which has shown deep degradation of its target with no detectable effects on other proteins. Preclinical studies demonstrate MRT-6160 inhibits disease progression in in vivo autoimmunity models.About Monte RosaMonte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot. Monta Rosa’s QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology and proteomics to identify degradable protein targets and rationally design MGDs with unprecedented selectivity. The QuEEN discovery engine enables access to a wide-ranging and differentiated target space of well-validated biology across multiple therapeutic areas. Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans oncology, autoimmune and inflammatory disease and beyond, and has a strategic collaboration with Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug. For more information, visit www.monterosatx.com   Forward-Looking StatementsThis communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained in herein include, but are not limited to, statements about our product development activities, including our expectations around the potential of molecular glue degraders, the potential of our pipeline of molecular glue degraders, including our molecular glue degrader for VAV1, known as MRT-6160, , our expectation of the relevance of our pre-clinical data for VAV1 and/or MRT-6160 and the potential relevance of such with respect to potential therapeutic utility in immunological and/or inflammatory disorders, our expectations regarding the advancement and timing of ongoing pre-clinical and clinical development of MRT-6160, including our estimated timing for filing of an investigational new drug application therefor, our ability to initiate clinical studies for MRT-6160, our expectations regarding potential therapeutic opportunities for VAV1 as a target and specifically for MRT-6160, our expectations regarding medical needs and potential therapeutic opportunities for MRT-6160. By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10-K for the year ended December 31, 2022, filed with the U.S. Securities and Exchange Commission on March 16, 2023, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance, or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations, or otherwise, except as required by applicable law. Investors Andrew Funderburk, Kendall IRir@monterosatx.com Media Cory Tromblee, Scient PRmedia@monterosatx.com

Oligonucleotide

26 Oct 2023

·www.biospace.com

Celltrion USA announces distribution and incorporation of YUFLYMA® (adalimumab-aaty), a Humira® biosimilar, to CarePartners Specialty Pharmacy Cost Savings Programs

YUFLYMA® (adalimumab-aaty) was first approved by the Food and Drug Administration on May 23, 2023 and became commercially available in the U.S. on July 2, 2023 The treatment will be available on CarePartners Specialty Pharmacy Program in late October and will make YUFLYMA accessible to over 10 million lives The inclusion of YUFLYMA creates greater accessibility to treatments for Americans JERSEY CITY, N.J.--(BUSINESS WIRE)-- Celltrion USA, Inc. (Celltrion USA) today announced its FDA-approved biosimilar, YUFLYMA® (adalimumab-aaty), has been added to CarePartners Specialty Pharmacy Cost Savings Programs. YUFLYMA is a high-concentration (100mg/mL) and citrate-free formulation of the Humira® (adalimumab) biosimilar. CarePartners and its strategic partners will offer and distribute YUFLYMA as the lowest net cost high-concentration Humira (adalimumab) biosimilar to over 10 million plan members. “Care Partners’ decision to add YUFLYMA to its formulary could benefit millions of Americans, bringing value to the healthcare system and patient communities,” said Thomas Nusbickel, Chief Commercial Offer at Celltrion USA. “We are dedicated to improving the lives of patients by expanding biosimilar access and affordability with treatment options backed by a strong, evidence-based efficacy-safety profile.” More than 80% of patients treated with Humira in the U.S. rely on a high-concentration and citrate-free formulation.1 YUFLYMA provides additional benefits of administration via a latex-free device and a longer shelf life due to its ability to maintain a stability at 77°F for a period up to 30 days, with protection from light. “We are excited to partner with Celltrion to offer a quality, high-concentration alternative to Humira at the lowest net-cost,” said Kam Ghazvini, RPh, Founder and CEO of CarePartners. “Partnering with Celltrion to offer YUFLYMA solidifies our cost saving initiatives for plan sponsors, employers, health plans, and other payers. We are excited to support Celltrion, a leading biotech company poised to be one of the leaders in the biosimilar landscape with a rich pipeline of blockbuster biosimilars in the years to come.” On September 29, the U.S. Food and Drug Administration (FDA) has approved additional strengths for YUFLYMA, a high-concentration (100mg/mL) and citrate-free formulation of Humira(adalimumab) biosimilar, in 20mg and 80mg strengths in the United States. <End> About YUFLYMA® (CT-P17, biosimilar adalimumab-aaty)2 YUFLYMA was the first high-concentration, low-volume, and citrate-free adalimumab biosimilar to receive European Commission approval in the European Union. 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. YUFLYMA is a recombinant fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody. Following the launch of 40mg/0.4mL in the U.S. in July 2023, two different types of dosage forms, 80mg/0.8mL, 20mg/0.2mL, were approved by the FDA on September 29, 2023. The full prescribing information can be found at: INDICATIONS YUFLYMA 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 YUFLYMA® IMPORTANT SAFETY INFORMATION SERIOUS INFECTIONS Patients treated with YUFLYMA 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 YUFLYMA 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 YUFLYMA use and during therapy. Initiate treatment for latent TB prior to YUFLYMA 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 YUFLYMA 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 YUFLYMA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Treatment with YUFLYMA 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 YUFLYMA if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with YUFLYMA, 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 YUFLYMA 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 YUFLYMA and other biologic products for the treatment of RA, PsA, AS, CD, UC, PS, and HS. Concomitant administration of YUFLYMA 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 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 YUFLYMA 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 YUFLYMA. In clinical trials of some adalimumab products, there was an approximate 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 several fold) 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 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 YUFLYMA and institute appropriate therapy. HEPATITIS B VIRUS REACTIVATION Use of TNF blockers, including YUFLYMA, 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 YUFLYMA 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 YUFLYMA 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 YUFLYMA in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of YUFLYMA 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 YUFLYMA 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 YUFLYMA 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 YUFLYMA, discontinue treatment. IMMUNIZATIONS Patients on YUFLYMA 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 YUFLYMA 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. Please see full Prescribing Information for YUFLYMA® (adalimumab-aaty) About Celltrion USA Celltrion USA is Celltrion Healthcare’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 USA will continue to leverage Celltrion Healthcare’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. Celltrion Healthcare endeavors to offer high-quality, cost-effective solutions through an extensive global network that spans more than 110 different countries. For more information, please visit: About CarePartners CarePartners is a specialty pharmacy business focused on providing chronic and complex therapies including specialty infusion, specialty pharmacy, and ambulatory infusion services. The CarePartners team is made up of experienced clinicians and experienced support staff dedicated to providing patients with the highest quality service, leveraging a high-touch patient centric model. CarePartners offers innovative cost saving programs with positive clinical outcomes to plan sponsors, employers, unions, PBMs, and health plans. CarePartners is fully accredited and is licensed to service patients in all 50 states and DC. References Symphony Health, IQVIA YUFLYMA US prescribing information (2023)

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D10320	Placulumab	-	DB11983

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Indication	Highest Phase	Country/Location	Organization	Date
Intervertebral Disc Displacement	Phase 2	US	Cephalon, Inc.	01 Jan 2011
Intervertebral Disc Displacement	Phase 2	AU	Cephalon, Inc.	01 Jan 2011
Radicular Pain	Phase 2	US	Cephalon, Inc.	01 Jan 2011
Radicular Pain	Phase 2	AU	Cephalon, Inc.	01 Jan 2011
Sciatica	Phase 2	US	Cephalon, Inc.	01 Jan 2011
Sciatica	Phase 2	AU	Cephalon, Inc.	01 Jan 2011
Rheumatoid Arthritis	Phase 2	LK	Arana Therapeutics Ltd.	01 Feb 2009
Inflammation	Phase 2	-	Teva Pharmaceutical Industries Ltd.	-
Inflammation	Phase 2	-	Domantis Ltd.	-
Psoriasis	Phase 2	-	Domantis Ltd.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2019	Not Applicable	Uveitis \| Nephritis, Interstitial	-	Adalimumab 40mg	indnxndwzn(rcsvrlbhju) = eoosiqmfsr qrimnxsxht (uftpabnnaf ) View more	-	05 Nov 2019
				Adalimumab 20mg	uyegtzbmbz(iivysrvdhj) = wicqlcfgvs nxiiyeyyzl (jyswkihcuw ) View more
ARVO2017	Not Applicable	Behcet Syndrome	-	Interferon alpha-2a	rzxvtngwxy(wenykqomjj) = spvxzubseg hajqqtlnlg (xvdiaulohd, (11 - 30)) View more	-	07 May 2017
				Anti TNF-alpha	rzxvtngwxy(wenykqomjj) = jcjeqyfqik hajqqtlnlg (xvdiaulohd, (6 - 20)) View more
BioColitis Registry (ECCO2016)	Not Applicable	Colitis, Ulcerative Maintenance	149	Anti-TNF alpha	wsfikvfykn(newjbnaalz) = pinirqurzy ycctzvdpxo (ynwoswhawh ) View more	Positive	12 Feb 2016
EULAR2015	Not Applicable	Rheumatoid Arthritis anti-nuclear antibodies (ANA)	74	Infliximab	gvspqiauby(pzcgobnrys) = etnktksodr qenheshmvi (wfqtwdwzwc )	Negative	10 Jun 2015
				Adalimumab	gvspqiauby(pzcgobnrys) = rorzsvvyyi qenheshmvi (wfqtwdwzwc )
not available (ACR2014)	Not Applicable	Behcet Syndrome TNF alpha \| soluble TNF receptors	122	Infliximab	ufubmweyav(hjkwbxqtmi) = Adverse events were reported in 28% of patients, mainly with infliximab (infliximab 61%, adalimumab 32%; p=0.02). They mainly included infections (52%) and hypersensitivity reactions (16%). Serious adverse events were reported in 13% of patients and required treatment interruption in all cases. rxncuwqroa (evufzcqsea ) View more	Positive	14 Nov 2014
EULAR2014	Not Applicable	Behcet Syndrome TNF alpha \| soluble TNF receptors	92	Anti-TNF alpha	xgzskontxs(favioxmbic) = Adverse events were reported in 26% of patients, mainly with infliximab. They included infections (19%), hypersensitivity reactions (2%), injection site reactions (2%), cancers (2%) and lupus (1%). Serious adverse events were reported in 8 patients (of whom 7 with infliximab) and required treatment interruption in all cases. skngzxkrsi (owudwkdpcg ) View more	Positive	11 Jun 2014
EULAR2014	Not Applicable	Non-infectious anterior uveitis TNF alpha	162	Infliximab	gywdgzcfbm(ffbomjxste) = 7% fyvajpkylj (hpvheitxkt ) View more	Positive	11 Jun 2014
				Adalimumab
EULAR2012	Not Applicable	Rheumatoid Arthritis LIGHT \| Cathepsin-K \| DKK-1 ... View more	-	Adalimumab 40 mg	posutwzucg(anzqnprwci) = dwcuqvrsdw yhsmlmpdpf (keazvwgufw, 11.3 - 15.3) View more	-	06 Jun 2012
				Anti TNF-ALPHA	posutwzucg(anzqnprwci) = fxhryecajm yhsmlmpdpf (keazvwgufw, 45 - 14.3) View more
ARVO2008	Not Applicable	Choroidal Neovascularization anti-TNF alpha antibody	-	Control (saline injection)	pzgdhrcfpe(vgdfldxauw) = vkomgmxxwt nujjpgwlfc (uxtqqvbnlg )	Positive	01 May 2008
				Infliximab 100µg	pzgdhrcfpe(vgdfldxauw) = cxxgvbfian nujjpgwlfc (uxtqqvbnlg, <0.05)

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