Itolizumab

20% of all subjects that completed the 24-week treatment period achieved SALT ≤ 20 29% of completed subjects with moderate to severe disease (baseline SALT 35 to <95) achieved SALT ≤ 20 EQ101 was well tolerated in subjects with alopecia areata with no serious adverse events reported Data supports advancing EQ101 development in alopecia areata to include dose and delivery optimization Data provides further support for opportunistic expansion in other dermatological conditions where IL-2, IL-9 and IL-15 inhibition is important such as vitiligo and atopic dermatitis LA JOLLA, Calif.--(BUSINESS WIRE)-- Equillium, Inc.. (Nasdaq: EQ), a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders, today announced positive topline data from its Phase 2, single dose, proof-of-concept (PoC) study of EQ101 in adult patients with moderate, severe or very-severe alopecia areata (AA), an autoimmune disease driven by an immune cell attack of the hair follicles that causes hair loss. The primary objectives of the study were to evaluate the safety and tolerability pro EQ101, as well as signs of efficacy using Severity of Alopecia Tool (SALT) scores, where a score of 100 represents total scalp hair loss and a score of 0 represents no scalp hair loss. Results from the study demonstrated a favorable safety and tolerability pro no serious adverse events (SAEs), and improvements in SALT scores above the published historically low placebo response rates. Of all subjects that completed 24 weeks of treatment (baseline SALT of 35 to 100, n=25), 20% achieved a SALT score of less than or equal to 20 by week 24. Of those subjects with moderate to severe AA at baseline that completed 24 weeks of treatment (SALT score 35 to < 95, n=17), 29% achieved a SALT score of less than or equal to 20 by week 24, and a mean SALT improvement from baseline of 18%. “The results from this Phase 2 proof-of-concept study of EQ101 in alopecia areata patients are very compelling,” said principal investigator, Rodney Sinclair, MD, Sinclair Dermatology, Melbourne, Victoria, Australia. “Placebo rates in this indication across studies have been consistently low – generally less than 10 percent of patients achieve a SALT score of 20 or less. To have 20 percent of patients completing the study reach a SALT score of less than or equal to 20 across all subjects, and 29 percent of moderate and severe patients, is a very encouraging sign of drug activity. With Janus kinase inhibitors currently the only approved therapies to treat alopecia areata, a significant unmet need remains for novel drug mechanisms that are effective and well tolerated; and the targeted multi-cytokine activity of EQ101 represents a welcome approach.” EQ101 is a novel multi-cytokine inhibitor with a targeted mechanism of action against cytokines IL-2, IL-9 and IL-15, which are key drivers of the pathogenic T cells implicated in AA. To be eligible for the Phase 2 study for the treatment of AA, subjects were required to have at least 35 percent scalp hair loss due to AA, as measured by SALT, and a current hair loss episode of at least six months, but not more than seven years. The study enrolled 36 subjects at multiple clinical trial sites, with a mean baseline SALT score of 76. Twenty-five subjects completed the study; eleven subjects discontinued the study early, of which only five were attributed to adverse events. Throughout 24 weeks of treatment and 4 weeks of follow up, EQ101 was well tolerated with no SAEs and no notable changes in safety laboratory (coagulation, hematology, chemistry, liver function, urinalysis, cholesterol), electrocardiogram, vital signs, or physical exam findings were reported. The majority (98.9%) of adverse events were Grade 1 or 2, with the most common being upper respiratory tract infection, headache and fatigue. The two (1.1%) Grade 3 events in two subjects considered related to study treatment were a case of transient lymphocytopenia and fatigue. Table 1 outlines response data on the 25 subjects that completed 24 weeks of treatment: Table 1 Completed Subjects (24 weeks of treatment) SALT Baseline by Subgroups n (%) Mean SALT @ Baseline SALT ≤ 20 @ W24 n (%) Mean SALT Improvement from Baseline @ W24 35 to <95 (moderate to severe) 17 (68%) 66.1 5 (29.4%) 18.4% 35 to <50 (moderate) 3 (12%) 39.9 2 (66.7%) 23.8% 50 to <95 (severe) 14 (56%) 71.8 3 (21.4%) 17.2% 95 to 100 (very severe, AU/AT*) 8 (32%) 99.8 0 (0.0%) 3.1% Completed Subjects 35 - 100 25 76.9 5 (20%) 13.5% * Alopecia areata universalis (AU) or totalis (AT) To better understand the depth of response in baseline SALT improvement, Equillium conducted an analysis of 21 subjects characterized as responders (excluding subjects that had a 20% or more increase in SALT score, n=4) as shown in Table 2: Table 2 Completed Subjects evaluated as Responders** SALT Baseline by Subgroups Mean SALT Improvement from Baseline @ W24 n (%) 35 to <95 (moderate to severe) 13 40.5% 35 to <50 (moderate) 2 78.8% 50 to <95 (severe) 11 33.5% 95 to 100 (very severe, AU/AT) 8 3.1% Responders Only: 35 - 100 21 26.3% ** Responders (n=21): excludes subjects that had a 20% or more increase in SALT score (n=4) In addition to these compelling signs of clinical activity, preliminary data indicate reductions of cell surface CD132 on both CD8 and NK cells in peripheral blood consistent with EQ101 target engagement and pharmacodynamic response. “We are very pleased with these positive clinical results, indicating EQ101 to be well-tolerated and clinically efficacious in alopecia areata patients with significant hair loss,” said Dr. Maple Fung, chief medical officer at Equillium. “We look forward to transitioning to a subcutaneous delivery in placebo-controlled, dose and regimen optimization studies where we expect to continue to investigate EQ101 across alopecia areata disease severity subgroups, including the important population of moderate patients with a SALT score between 35 and less than 50. Though hair loss is lower in patients with moderate disease, the impact on their quality of life is very much in line with more severe patients, yet current systemic Janus kinase inhibitor therapies are only approved for patients with severe disease.” A presentation outlining the data is available on the “Events & Presentations” page under the Investor Relations tab on the Company’s website at . About EQ101 Phase 2 Study in Alopecia Areata This was a multicenter, open-label, proof-of-concept Phase 2 study in 36 adult subjects between 18 and 60 years of age, with at least 35% scalp hair loss due to alopecia areata (AA) with a current hair loss episode of at least 6 months but not more than 7 years. Subjects were dosed intravenously once weekly for 24 weeks with EQ101 at a dose level of 2 mg/kg, and subsequently followed for an additional four weeks. The primary objective of the study was to evaluate the safety pro tolerability of EQ101 in subjects with moderate to very severe AA over a 24-week treatment period; secondary objectives included the evaluation of drug efficacy, pharmacokinetic/pharmacodynamic (PK/PD) properties, and assessment of changes in patient biomarkers. About Alopecia Areata Alopecia areata (AA) is a common, inflammatory, non-scarring condition resulting in hair loss that occurs when the immune system attacks hair follicles on any hair-bearing area of the body, most frequently on the head and face. The lifetime incidence of AA is estimated at about two percent globally, affecting men and women of all racial and ethnic groups. It has a higher prevalence in children and adolescents with 40% of cases occurring prior to age 20, and 80% before age 40. AA is associated with other immune-mediated or autoimmune disorders such as thyroiditis, vitiligo, and atopic diseases. Approximately 50% of patients have chronic relapsing, remitting disease persisting more than 12 months and approximately 10% to 35% ultimately experience complete loss of scalp hair (alopecia totalis, or AT) or complete loss of scalp and body hair (alopecia universalis, or AU). AA has a significant psychosocial burden that can have a significant negative impact on health-related quality of life and has been associated with depression and anxiety. There are currently limited treatment options and few countries have approved drugs for the treatment of AA. IL-2, IL-9, and IL-15 are cytokines of the common gamma chain receptor known to be upregulated in animal models and human biopsies of AA and may provide a selective and potent approach to disease treatment. About Multi-Cytokine Platform and Multi-Cytokine Inhibitors EQ101 & EQ302 Our proprietary multi-cytokine platform generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. This approach is expected to avoid the broad immuno-suppression and off-target safety liabilities that may be associated with other therapeutic classes, such as Janus kinase inhibitors. Many immune-mediated diseases are driven by the same combination of dysregulated cytokines, and we believe identifying the key cytokines for these diseases will allow us to target and develop customized treatment strategies for multiple autoimmune and inflammatory diseases. Current platform assets include EQ101, a clinical stage, first-in-class, selective, tri-specific inhibitor of IL-2, IL-9, and IL-15 for intravenous and subcutaneous delivery, and EQ302, a preclinical stage, first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21 for oral delivery. About Equillium Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of the following novel first-in-class immunomodulatory assets and product platform targeting immuno-inflammatory pathways. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15; recently announced positive results from a Phase 2 proof-of-concept clinical study of patients with alopecia areata in Australia and New Zealand by Equillium’s Australian subsidiary as the trial sponsor. EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21; currently in pre-clinical development. The multi-cytokine platform: generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells; currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and recently completed a Phase 1b clinical study of patients with lupus/lupus nephritis. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited and has entered a strategic partnership with Ono Pharmaceutical Co., Ltd., for the development and commercialization of itolizumab under an option and asset purchase agreement. For more information, visit . Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking Statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements include, but are not limited to, statements regarding Equillium’s plans for further developing EQ101, EQ302 and itolizumab and the expected timeline for initiation of and results from clinical studies, and the potential benefits of Equillium’s product candidates. Because such statements are subject to risks and uncertainties, many of which are outside of Equillium’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: Equillium’s ability to execute its plans and strategies; risks related to performing clinical and pre-clinical studies; whether the results from clinical and pre-clinical studies will validate and support the safety and efficacy of Equillium’s product candidates; changes in the competitive landscape; the risk that the FDA will expand the use of approved JAK inhibitors for the treatment of moderate AA; uncertainties related to Equillium’s capital requirements; and having to use cash in ways or on timing other than expected and the impact of market volatility on cash reserves. These and other risks and uncertainties are described more fully under the caption "Risk Factors" and elsewhere in Equillium's filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website and on Equillium’s website under the heading “Investors.” Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. Equillium undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

More than 100 patients enrolled from over 100 clinical trial sites active in 12 countries Delivery of the interim data review to Ono Pharmaceutical Co. Ltd. (Ono) expected during Q3 will trigger Ono’s option exercise period LA JOLLA, Calif.--(BUSINESS WIRE)-- Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company focused on developing novel therapeutics to treat severe autoimmune and inflammatory disorders, today announced that it has surpassed the interim enrollment target for the Phase 3 EQUATOR study of itolizumab in acute graft-versus-host disease (aGVHD). Equillium expects to deliver the results of the EQUATOR interim data review to Ono during the third quarter, which will then trigger Ono’s three-month option exercise period to acquire Equillium’s rights to itolizumab. “Our clinical development team has done an excellent job of recruiting and activating trial sites globally,” said Bruce Steel, chief executive officer at Equillium. “While the interim data will be blinded to Equillium and Ono, our independent data monitoring committee will conduct an unblinded analysis of the data and make a recommendation whether the study should proceed to conclusion based on pre-determined futility and efficacy stopping boundaries. Having now met the enrollment threshold for the interim review, we believe we are well on track to meet our guidance of delivering this final data milestone to Ono during the third quarter, setting the timeline for Ono’s option exercise decision to acquire itolizumab, which will expire three months following delivery of the results of the interim analysis.” If Ono exercises the option, Ono will pay Equillium a one-time payment of JPY 5.0 billion, or approximately $32.2 million based on the currency exchange rate on May 8, 2024. Equillium is also eligible to receive up to $101.4 million upon the achievement of certain development, regulatory, and commercialization milestones. About the EQUATOR Study The Phase 3, randomized, double-blind, placebo-controlled multicenter study (NCT05263999) will compare the efficacy and safety of IV administered itolizumab versus placebo (randomized 1:1) as a first-line therapy in approximately 200 adult and adolescent patients with Grade III-IV aGVHD, or Grade II aGVHD with lower GI involvement, in combination with high doses of corticosteroids, the current standard of care. The primary study endpoint is complete response rate at Day 29; key secondary endpoints include overall response rate at Day 29 and durability of complete response rate from Day 29 through Day 99. Per the study protocol, patients must receive itolizumab within 3-days of the first administration of high-dose corticosteroids with a treatment period from Days 1-99, and a follow-up period from Days 100-365. Approximately 200 eligible subjects will receive 2 mg/kg methylprednisolone or equivalent on Day 1 and will be randomized in a 1:1 ratio to the following two treatment groups: Group A: Itolizumab, 1.6 mg/kg initial dose followed by 6 doses of 0.8 mg/kg once every 2 weeks (q2w), plus systemic corticosteroids (100 subjects) Group B: Placebo, 7 doses q2w, plus systemic corticosteroids (100 subjects) An independent data monitoring committee will regularly review safety data, and an interim analysis for both futility and efficacy will be conducted after approximately 100 subjects have completed Day 29 assessments. About Itolizumab Itolizumab is a clinical-stage, first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to selectively downregulate pathogenic T effector cells while preserving T regulatory cells critical for maintaining a balanced immune response. This pathway plays a central role in modulating the activity and trafficking of T cells that drive a number of immuno-inflammatory diseases. About Equillium Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of the following novel first-in-class immunomodulatory assets and product platform targeting immuno-inflammatory pathways. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15; currently under evaluation in a Phase 2 proof-of-concept clinical study of patients with alopecia areata being conducted in Australia and New Zealand by Equillium’s Australian subsidiary as the trial sponsor. EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21; currently in pre-clinical development. The multi-cytokine platform: generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells; currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and recently completed a Phase 1b clinical study of patients with lupus/lupus nephritis. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited and has entered a strategic partnership with Ono Pharmaceutical Co., Ltd., for the development and commercialization of itolizumab under an option and asset purchase agreement. For more information, visit . Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements include, but are not limited to, statements regarding Equillium’s plans to deliver the results of the interim review of the EQUATOR study to Ono Pharmaceutical and related timing thereof, the timing for triggering Ono’s option period and for receiving Ono’s option decision, plans for developing EQ101, EQ302 and itolizumab, the expected timeline for results from clinical studies, anticipated upcoming milestones, the fluctuation of the foreign exchange rate, and the potential benefits of Equillium’s product candidates. Because such statements are subject to risks and uncertainties, many of which are outside of Equillium’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: Equillium’s ability to execute its plans and strategies; risks related to performing clinical and pre-clinical studies; whether the results from clinical and pre-clinical studies will validate and support the safety and efficacy of Equillium’s product candidates; Equillium’s plans and product development, including the initiation and completion of clinical studies and the reporting of data therefrom; changes in the competitive landscape; risks related to Ono’s financial condition and decision to exercise its option, if ever, to purchase itolizumab or terminate the asset purchase agreement; and uncertainties related to Equillium’s capital requirements. These and other risks and uncertainties are described more fully under the caption "Risk Factors" and elsewhere in Equillium's filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website and on Equillium’s website under the heading “Investors.” Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. Equillium undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.