Barzolvolimab

HAMPTON, N.J., May 15, 2024 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced that the first patient has been dosed in the Company’s Phase 2 subcutaneous study of barzolvolimab in prurigo nodularis (PN). Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity, which is required for the function and survival of the mast cell. Mast cells are believed to play an important role in amplifying chronic itch and neuroinflammation, including in PN where mast cells are associated with pruritic sensory neurons in PN lesions. In November 2023, Celldex presented first in class data from the Company’s Phase 1b study in PN demonstrating that barzolvolimab and its novel mast cell depleting mechanism could play a meaningful role in breaking the stubborn scratch/itch cycle of this disease, resulting in lesion healing. “Prurigo nodularis is a miserable disease and treatment options are desperately needed that offer early and durable relief by both reducing the relentless itching associated with the disease and allowing for healing of the painful lesions that are the hallmark of PN,” said Diane C. Young, M.D, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. “In our Phase 1b PN study, with just a single dose of barzolvolimab, we demonstrated remarkable clinical results. We are very excited to see what multiple doses of barzolvolimab may offer patients in this important Phase 2 study.” The randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety pro 2 dose levels of barzolvolimab compared to placebo in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable (such as concerns for safety), including patients who received prior biologics. Patients will be randomly assigned on a 1:1:1 ratio to receive barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week treatment phase. Participants will then enter a follow-up phase with no study treatment for an additional 16 weeks through week 40. The primary objective of this study is to evaluate the clinical effect of barzolvolimab, compared to placebo, on itch response as measured by the proportion of participants with ≥ 4-point improvement in the worst intensity itch per a numeric rating scale (WI-NRS). Secondary objectives include but are not limited to additional measures of itch response from baseline compared to different timepoints, the assessment of skin lesions as measured by the Investigator Global Assessment (IGA), QoL outcomes and safety. The study will include approximately 50 clinical trial centers worldwide, including the United States. For additional information on this trial (NCT06366750), please visit . About Prurigo Nodularis (PN) PN is a chronic skin disease that causes hard, intensely itchy lumps/nodules to form on the skin. The itching (pruritus) can be intense, causing people to scratch themselves to the point of bleeding or pain, which can form lesions and perpetuate the disease cycle. With limited treatment options available, PN is also associated with significant impact on quality of life including sleep disturbance, psychological distress, social isolation, anxiety and depression. Mast cells are believed to play an important role in amplifying chronic itch and neuroinflammation, including in PN where mast cells are associated with pruritic sensory neurons in PN lesions. About Barzolvolimab Barzolvolimab 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 . 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 Contact Sarah Cavanaugh Senior Vice President, Corporate Affairs & Administration (508) 864-8337 scavanaugh@celldex.com Patrick Till Meru Advisors (484) 788-8560 ptill@meruadvisors.com

- Phase 3 CSU studies expected to initiate in summer 2024 - - Positive Phase 2 CSU 12 week data reported in late breaking oral presentation at AAAAI 2024; 52 week data to be reported in 2H 2024 - - Enrollment completed in Phase 2 CIndU study; 12 week data expected 2H 2024 - - Phase 2 PN study initiated; enrollment progressing in Phase 2 EoE study - - Atopic dermatitis selected as next indication; Phase 2 study to initiate by YE 2024 - HAMPTON, N.J., May 06, 2024 (GLOBE NEWSWIRE) -- Celldex Therapeutics Inc. (NASDAQ:CLDX) today reported financial results for the first quarter ended March 31, 2024 and provided a corporate update. "During the first quarter we presented impressive best-in-field data from a large, randomized Phase 2 study in CSU,” said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. “These results added to a rapidly growing body of data across multiple indications that support barzolvolimab’s impressive potential to treat mast cell mediated diseases. This year, we continue to expand barzolvolimab’s pro based on its unique mechanism of action and demonstrated improvement in pruritus, we are actively planning for the initiation of a Phase 2 study in atopic dermatitis, a setting where mast cell numbers are known to be increased and activated in the lesions associated with the disease and where, despite established systemic therapies, a significant unmet need still exists.” Mr. Marucci continued, “As the year progresses, we look forward to building on our leadership in the development of mast cell-targeted therapeutics. Importantly, the Company is well capitalized with more than $820M in cash to support the continued advancement and expansion of the barzolvolimab program and the introduction of our first bispecific for inflammatory diseases later this year.” Recent Program Highlights Barzolvolimab - KIT Inhibitor Program Barzolvolimab is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase 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. Celldex is conducting Phase 2 clinical studies of barzolvolimab for the treatment of chronic spontaneous urticaria (CSU) and the two most common forms of chronic inducible urticaria (CIndU) - cold urticaria (ColdU) and symptomatic dermographism (SD). These randomized, double-blind, placebo-controlled Phase 2 studies are evaluating the efficacy and safety pro multiple dose regimens of barzolvolimab in patients who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategies. Celldex is currently planning two Phase 3 studies of barzolvolimab in CSU, which are expected to initiate this summer. In February 2024, 12 week treatment results were reported from the Phase 2 CSU study at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in a late breaking oral presentation. Barzolvolimab achieved the primary efficacy endpoint of the study, with a statistically significant mean change from baseline to week 12 of UAS7 (weekly urticaria activity score) compared to placebo across multiple dosing groups and was well tolerated. Secondary and exploratory endpoints in the study, including ISS7 (weekly itch severity score) and HSS7 (weekly hives severity score) and responder analyses strongly support the primary endpoint results. Importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. 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 study will continue to receive barzolvolimab for 52 weeks and the Company plans to report 52 week data in the second half of 2024. Data from this study on the impact of barzolvolimab on angioedema have been accepted for an oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024 on Saturday, June 2nd from 3:00-4:30 CET in Valencia, Spain (9:00-10:30 am ET). Enrollment to the Phase 2 CIndU study has been completed and 12 week primary endpoint data from this study are expected to be reported in the second half of 2024. The study enrolled 196 patients—97 patients with cold urticaria and 99 patients with symptomatic dermographism. A Phase 2 subcutaneous study in prurigo nodularis (PN) was initiated in early 2024. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety pro barzolvolimab in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable, including patients who received prior biologics. Patients are receiving barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week Treatment Phase. In July 2023, the first patient was dosed in the Phase 2 randomized, double-blind, placebo-controlled study in eosinophilic esophagitis (EoE); enrollment is ongoing. To optimize potential efficacy signal in this difficult to treat indication, in early 2024, the protocol was amended to dose 300 mg every 4 weeks rather than 8 weeks. Approximately 75 patients will be enrolled in total. Atopic Dermatitis has been selected as the fifth indication for the development of barzolvolimab. Atopic dermatitis (AD) is a chronically relapsing, inflammatory skin disease that is typified by pruritus (itching), eczematous lesions, dry skin, thickening of the skin and an increase in skin markings. AD is the most common inflammatory skin condition, with a lifetime prevalence of up to 20% and has a high itch burden—almost 90% of individuals with AD experience daily itching and 60% describe their itching as severe or unbearable. Barzolvolimab’s novel mast cell depleting mechanism could play an important role in addressing patients with moderate to severe AD who do not achieve complete disease control on currently available systemic therapies. Mast cell numbers are increased and activated in AD lesions and produce key TH2 cytokines and neuropeptides that trigger disease progression and itch. Barzolvolimab has demonstrated impressive anti-pruritic effects in other itch driven conditions, including chronic urticarias and prurigo nodularis. Celldex plans to initiate a Phase 2 study in AD by year end. Bispecific Antibody Platform CDX-585–Bispecific ILT4 & PD-1 CDX-585 combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. ILT4 is emerging as an important immune checkpoint on myeloid cells. In May 2023, the first patient was dosed in the Phase 1 study of CDX-585. This open-label, multi-center study of CDX-585 is evaluating patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. Enrollment is ongoing in the dose-escalation portion of the study. First Quarter 2024 Financial Highlights and 2024 Guidance Cash Position: Cash, cash equivalents and marketable securities as of March 31, 2024 were $823.8 million compared to $423.6 million as of December 31, 2023. The increase was primarily driven by net proceeds of $432.3 million from our March 2024 underwritten public offering, partially offset by cash used in operating activities of $40.6 million. At March 31, 2024, Celldex had 65.9 million shares outstanding. Revenues: Total revenue was $0.2 million in the first quarter of 2024, compared to $1.0 million for the comparable period in 2023. The decrease in revenue was primarily due to a decrease in services performed under our manufacturing and research and development agreements with Rockefeller University. R&D Expenses: Research and development (R&D) expenses were $31.7 million in the first quarter of 2024, compared to $26.8 million for the comparable period in 2023. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial and personnel expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses. G&A Expenses: General and administrative (G&A) expenses were $9.1 million in the first quarter of 2024, compared to $6.6 million for the comparable period in 2023. The increase in G&A expenses was primarily due to an increase in stock-based compensation and barzolvolimab commercial planning expenses. Net Loss: Net loss was $32.8 million, or ($0.56) per share, for the first quarter of 2024, compared to a net loss of $29.4 million, or ($0.62) per share, for the comparable period in 2023. Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at March 31, 2024 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027. 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 . 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 Contact Sarah Cavanaugh Senior Vice President, Corporate Affairs & Administration (508) 864-8337 scavanaugh@celldex.com Patrick Till Meru Advisors (484) 788-8560 ptill@meruadvisors.com CELLDEX THERAPEUTICS, INC. (In thousands, except per share amounts) Three Months Consolidated Statements of Operations Data Ended March 31, 2024 2023 (Unaudited) Revenues: Product development and licensing agreements $ 2 $ - Contracts and grants 154 967 Total revenues 156 967 Operating expenses: Research and development 31,661 26,798 General and administrative 9,103 6,640 Total operating expenses 40,764 33,438 Operating loss (40,608 ) (32,471 ) Investment and other income, net 7,800 3,110 Net loss $ (32,808 ) $ (29,361 ) Basic and diluted net loss per common share $ (0.56 ) $ (0.62 ) Shares used in calculating basic and diluted net loss per share 58,871 47,214 Condensed Consolidated Balance Sheet Data March 31 December 31, 2024 2023 (Unaudited) Assets Cash, cash equivalents and marketable securities $ 823,846 $ 423,598 Other current assets 11,478 8,095 Property and equipment, net 4,061 4,060 Intangible and other assets, net 29,462 29,874 Total assets $ 868,847 $ 465,627 Liabilities and stockholders' equity Current liabilities $ 26,291 $ 31,125 Long-term liabilities 3,943 5,331 Stockholders' equity 838,613 429,171 Total liabilities and stockholders' equity $ 868,847 $ 465,627