Omalizumab

- Clinically meaningful and statistically significant improvements across multiple angioedema measurements and barzolvolimab dose groups -- Sustained activity with rapid onset within 2 weeks -- Data further support barzolvolimab clinical benefit to patients with CSU - HAMPTON, N.J., June 02, 2024 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced data demonstrating that barzolvolimab profoundly improves angioedema at 12 weeks in the Company’s Phase 2 clinical trial in chronic spontaneous urticaria (CSU). Angioedema, characterized by swelling of the deeper dermal layers of the skin and mucous membranes, is a painful, debilitating symptom of CSU that has significant impact on quality of life. It commonly affects the face (lips and eyelids), hands, feet, and genitalia but can also involve the tongue, uvula, soft palate, and pharynx1. The data were presented today by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin, in an oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024. Celldex previously announced that the Phase 2 study in CSU met its primary and secondary endpoints at 12 weeks with clinically meaningful and statistically significant decreases in UAS7 (weekly urticaria activity score) compared to placebo across multiple dose groups and demonstrated a favorable safety profile. The data presented today further support these results by demonstrating improvements in AAS7 (weekly angioedema activity score) and additional measures of angioedema control. “The majority of patients with severe CSU suffer with angioedema, which is often extremely painful and causes disfigurement, dramatically impacting quality of life,” said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. "Consistent with previously reported clinical outcomes, we observed rapid, durable and significant angioedema relief, including in omalizumab refractory disease. These data continue to support barzolvolimab’s potential to become a transformative treatment option for CSU and we look forward to moving closer to this goal with the initiation of our Phase 3 studies this summer.” Phase 2 Barzolvolimab Study in CSU (n=208)Summary of Angioedema Clinical Activity Assessments at Week 12 300 mg Q8W(n=51)150 mg Q4W(n=52)75 mg Q4W(n=53)Placebo(n=51)Angioedema at baseline, n (%)42 (82%)35 (67%)40 (75%)32 (63%)AAS7 ChangesBaseline AAS7 (mean)53.1554.6054.0556.30LS Mean difference from placebo (Confidence Interval, p value)-25.32 (CI:-36.32, -14.32)p<0.0001-23.56(CI:-35.08, -12.04)p<0.0001-17.52(CI:-29.35, -5.69)p=0.0039 >8 point improvement in AAS7 (%)85.0P<0.0587.1P<0.0582.9P<0.0557.1Angioedema Free Days (mean)65.1P<0.0554.5P<0.0543.336.2AAS7 data were analyzed using ANCOVA model and multiple imputation. Data are presented for patients with angioedema at baseline. Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at Week 12. This improvement was rapid (within 2 weeks) and durable (continued through 12 weeks).Barzolvolimab demonstrated strong improvement in AAS7 independent of omalizumab status at Week 12. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action.Patients on barzolvolimab experienced a > 8 point improvement in AAS7 (considered a clinically meaningful result) across all doses compared to placebo (p<0.05).Barzolvolimab increased angioedema free days compared to placebo through 12 weeks. Patients in the 300 mg cohort were angioedema free 77% of the time over the 12 week period. Phase 2 Study Design The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CSU who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment period. After 16 weeks, patients then enter a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose are randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remain on the same regimen as during the placebo-controlled treatment period. After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to Week 12 in UAS7 (weekly activity score). Secondary endpoints include other assessments of safety and clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hives severity score) and AAS7 (weekly angioedema activity score). For additional information on this trial (NCT05368285), please visit www.clinicaltrials.gov 1DermNet. About Chronic Spontaneous Urticaria (CSU)CSU is characterized by the occurrence of hives or wheals for 6 weeks or longer without identifiable specific triggers or causes. The activation of the mast cells in the skin (release of histamines, leukotrienes, chemokines) results in episodes of itchy hives, swelling and inflammation of the skin that can go on for years or even decades. Current therapies provide symptomatic relief only in some patients. About BarzolvolimabBarzolvolimab is a humanized monoclonal antibody that binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. In certain inflammatory diseases, such as chronic urticaria, mast cell activation plays a central role in the onset and progression of the disease. Barzolvolimab is currently being studied in chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), prurigo nodularis (PN) and eosinophilic esophagitis (EOE) with additional indications planned for the future, including atopic dermatitis (AD). About Celldex Therapeutics, Inc.Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with severe inflammatory, allergic, autoimmune and other devastating diseases. Visit www.celldex.com. Forward Looking Statement This release contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct or that those goals will be achieved, and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to successfully complete research and further development and commercialization of Company drug candidates, including barzolvolimab (also referred to as CDX-0159), in current or future indications; the uncertainties inherent in clinical testing and accruing patients for clinical trials; our limited experience in bringing programs through Phase 3 clinical trials; our ability to manage and successfully complete multiple clinical trials and the research and development efforts for our multiple products at varying stages of development; the availability, cost, delivery and quality of clinical materials produced by our own manufacturing facility or supplied by contract manufacturers, who may be our sole source of supply; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; our ability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; our ability to continue to obtain capital to meet our long-term liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials that we have initiated or plan to initiate; and other factors listed under "Risk Factors" in our annual report on Form 10-K and quarterly reports on Form 10-Q. All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise. Company ContactSarah CavanaughSenior Vice President, Corporate Affairs & Administration(508) 864-8337scavanaugh@celldex.com Patrick TillMeru Advisors(484) 788-8560ptill@meruadvisors.com

Patients treated with remibrutinib experienced improvements in weekly urticaria activity scores (UAS7) observed as early as Week 1 and sustained to 1 year (Week 52)1 Remibrutinib, an oral Bruton’s tyrosine kinase inhibitor, demonstrated a favorable and consistent safety profile up to 1 year, including balanced liver function tests versus placebo1 Novartis intends to submit remibrutinib for approval in chronic spontaneous urticaria (CSU) to global health authorities starting in H2 2024, and continues to investigate remibrutinib in multiple immune-mediated conditions Data reaffirm the first-in-class potential of remibrutinib for the more than 50% of patients with CSU uncontrolled by H1-antihistamines who continue to live with painful and debilitating symptoms1,2 May 31, 2024 – Novartis today announced new data that confirm the long-term efficacy and safety of remibrutinib, a highly selective Bruton’s tyrosine kinase (BTK) inhibitor, in chronic spontaneous urticaria (CSU)1. In the pivotal Phase III studies, REMIX-1 and REMIX-2, remibrutinib treatment showed significant symptom improvement early, which was sustained up to Week 52, in patients with CSU who remained symptomatic despite second-generation H1-antihistamine use1. These data are being presented at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Congress in Valencia, Spain, May 31–June 3. “A large majority of people with CSU are living with uncontrolled and debilitating symptoms, often trying to manage the condition by cycling through antihistamines at higher doses with no lasting respite, impacting heavily on their day-to-day lives,” said Martin Metz, Professor of Dermatology, Charité – Universitätsmedizin Berlin, Germany. “Remibrutinib has become an important investigational treatment for CSU as it blocks the BTK cascade and inhibits the release of histamine. These data show that remibrutinib has the potential to offer patients and physicians a well-tolerated oral treatment that provides early and lasting efficacy.” New long-term Phase III REMIX-1 and REMIX-2 data assessed at Week 52 show that1: Significant improvements with remibrutinib versus placebo, as previously shown at Week 12, were confirmed at Week 24, including in weekly urticaria activity score (UAS7), weekly itch severity score (ISS7), and weekly hive severity score (HSS7) At Week 24, patients receiving placebo were transitioned to remibrutinib; responses with remibrutinib were observed as early as the first week after switching and were sustained until the end of the study (28 weeks of treatment) Almost half of patients were completely free of itch and hives (UAS7=0) as assessed at Week 52 “Living with CSU can be very distressing due to its unpredictable nature and never knowing when a flare-up may happen. Symptoms can occur on the face, throat, hands, and feet, and people may experience burning and pain on their skin,” said Tonya Winders, President and CEO, Global Allergy and Airways Patient Platform. “Unfortunately, many people continue to cope with uncontrolled symptoms. We welcome further research advancing our knowledge about chronic spontaneous urticaria.” Remibrutinib was well-tolerated and demonstrated a favorable and consistent safety profile up to 52 weeks, including balanced liver function tests versus placebo1. Adverse events (AEs), including serious AEs and treatment discontinuations due to AEs, were comparable between remibrutinib and placebo during the 24-week placebo-controlled period1. In addition, exposure-adjusted rates did not increase with long-term treatment1. Liver transaminase elevations were balanced across the remibrutinib and placebo treatment groups; all were asymptomatic, transient, and reversible1. None of the serious AEs were considered related to study medication by investigators. “Urticaria is a disease that significantly impacts patients' quality of life and there is an urgent need for new treatment options,” said Angelika Jahreis, Global Head, Development, Immunology, Novartis. “The 52-week REMIX-1 and REMIX-2 Phase III data are significant as many patients who had moderate to severe urticaria at study start were completely free of itch and hives after 52 weeks of treatment and remibrutinib, a highly selective oral BTK inhibitor, continued to be well tolerated. These exciting long-term data will be submitted to global health authorities later this year.” In addition to CSU, remibrutinib is being investigated in several other immune-mediated conditions, such as hidradenitis suppurativa, where it met its primary endpoint in a Phase II study3. It is also being investigated in food allergy, chronic inducible urticaria, and multiple sclerosis4-8. Novartis will submit remibrutinib for approval in CSU to global health authorities starting in H2 2024. Remibrutinib is an investigational, highly selective, covalent, oral BTK inhibitor that blocks the BTK cascade and prevents the release of histamine that causes itchy hives (wheals) and swelling9-11. When remibrutinib is used alongside standard-dose antihistamines, it results in a “two-pronged approach” where two parts of the inflammatory pathway are targeted, with remibrutinib inhibiting histamine release and antihistamines inhibiting histamine receptors, reducing CSU symptoms12,13. In the pivotal Phase III studies, REMIX-1 and REMIX-2, remibrutinib met all primary endpoints in patients with CSU who remained symptomatic despite second-generation H1-antihistamine use1. Treatment with remibrutinib showed significant symptom improvement early, which was sustained up to Week 521. Remibrutinib has been shown to be well-tolerated, with a favorable safety profile up to 52 weeks, including balanced liver function tests versus placebo1. Most commonly (≥5%) observed AEs in the Phase III REMIX studies were respiratory tract infections (including COVID-19 and nasopharyngitis) and headache, all comparable with placebo1,14. If approved in CSU, remibrutinib would offer an effective oral option within the Novartis immunology portfolio, which currently includes Xolair® (omalizumab), the first and only injectable biologic indicated for CSU15. In the US, Novartis Pharmaceuticals Corporation and Genentech, a member of the Roche Group, work together to develop and co-promote Xolair. In addition to CSU, remibrutinib is being investigated in several other immune-mediated conditions and has the potential to be a pipeline in a product4-8. REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) are two identically designed, global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III studies, with REMIX-1 consisting of 470 participants and REMIX-2 consisting of 455 participants16,17. Both studies are designed to establish the efficacy, safety, and tolerability of twice-daily remibrutinib 25 mg treatment in adult participants with CSU that is inadequately controlled by second-generation H1-antihistamines compared with placebo1,16,17. The primary outcome measures were absolute change from baseline in weekly urticaria activity score (UAS7) as well as weekly itch severity score (ISS7) and weekly hive severity score (HSS7) at Week 1216,17. All participants were on a stable, local label-approved dose of a second-generation H1-antihistamine throughout the entire study16,17. CSU is the medical term for chronic hives that last for 6 weeks or longer, where the underlying cause is internal rather than exposure to any allergen or external trigger2,11,18. CSU affects approximately 40 million people worldwide2,19. It is characterized by the sudden appearance of itchy hives (wheals) and/or deep tissue swelling (angioedema, which can occur on the face, throat, hands, and feet)11,20. CSU affects all ages but occurs most frequently between the ages of 20–40 years, with women affected nearly twice as often as men2. CSU causes significant emotional distress, with the majority of patients suffering from sleep deprivation, and high rates of mental disorders, such as anxiety or depression, as well as impacting on their work productivity2. Antihistamines are often prescribed for CSU as they block histamine receptors and prevent the pro-inflammatory action of histamine, which causes itching and swelling13,18. However, more than 50% of people with CSU are uncontrolled by H1-antihistamines alone2. Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. References Metz M, Giménez-Arnau A, Hide M, et al. Long-term efficacy and safety of remibrutinib in patients with chronic spontaneous urticaria in the Phase 3 REMIX-1 and REMIX-2 studies. Presented as a late oral abstract session on clinical trials at EAACI 2024; May 31-June 3, 2024; Valencia, Spain. Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA²LEN task force report. Allergy 2011; 66: 317-330. Kimball A, Prens E, Bechara F, et al. Efficacy and safety of the oral Bruton’s tyrosine kinase inhibitor, remibrutinib, in patients with moderate to severe hidradenitis suppurativa in a randomized, phase 2, double-blind, placebo-controlled platform study. Presented as a late-breaking abstract at the American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, California. ClinicalTrials.gov. NCT05147220. Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis. Available from: https://clinicaltrials.gov/study/NCT05147220 [Last accessed: May 2024]. ClinicalTrials.gov. NCT05156281. Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis (RMS) (REMODEL-2). Available from: https://clinicaltrials.gov/study/NCT05156281 [Last accessed: May 2024]. ClinicalTrials.gov. NCT03827798. Study of efficacy and safety of investigational treatments in patients with moderate to severe hidradenitis suppurativa. Available from: https://clinicaltrials.gov/ct2/show/NCT03827798. [Last accessed: May 2024]. ClinicalTrials.gov. NCT05432388. Study of efficacy, safety and tolerability of remibrutinib in adult participants with an allergy to peanuts. Available from: https://clinicaltrials.gov/study/NCT05432388 [Last accessed: May 2024]. ClinicalTrials.gov. NCT05976243. Study to investigate efficacy, safety, and tolerability of remibrutinib compared with placebo in adults with CINDU inadequately controlled by H1-antihistamines. Available from: https://clinicaltrials.gov/study/NCT05976243. [Last accessed: May 2024]. Maurer M, Berger W, Giménez-Arnau A, et al. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. J Allergy Clin Immunol 2022; 150: 1498-1506. Angst D, Gessier F, Janser P, et al. Discovery of LOU064 (remibrutinib), a potent and highly selective covalent inhibitor of Bruton's Tyrosine Kinase. J Med Chem 2020; 63: 5102-5118. Powell RJ, Leech SC, Till S, et al. BSACI guideline for the management of chronic urticaria and angioedema. Clin Exp Allergy 2015; 45: 547-565. Jain V, Giménez-Arnau A, Hayama K, et al. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. J Allergy Clin Immunol 2024; 153: 479-486. Patient. Antihistamines. Last updated 12 October 2022. Available from: https://patient.info/allergies-blood-immune/allergies/antihistamines [Last accessed: May 2024]. Novartis. Data on file. Genentech USA, Inc. and Novartis Pharmaceuticals Corporation. Xolair Omalizumab. Chronic Spontaneous Urticaria (CSU). Available from: https://www.xolair.com/chronic-spontaneous-urticaria.html [Last accessed: May 2024]. ClinicalTrials.gov. NCT05030311. A Phase 3 study of efficacy and safety of remibrutinib in the treatment of CSU in adults inadequately controlled by H1 antihistamines (REMIX-1). Available from: https://clinicaltrials.gov/study/NCT05030311 [Last accessed: May 2024]. ClinicalTrials.gov. NCT05032157. A Phase 3 study of efficacy and safety of remibrutinib in the treatment of CSU in adults inadequately controlled by H1- antihistamines (REMIX-2). Available from: https://clinicaltrials.gov/study/NCT05032157 [Last accessed: May 2024]. Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy 2022; 77: 734-766. The content above comes from the network. if any infringement, please contact us to modify.