Equillium Announces Positive Topline Data from the Type B Portion of the Phase 1b EQUALISE Study of Itolizumab in Lupus Nephritis

Topline data delivered to Ono Pharmaceutical, representing the first of two data sets that will trigger Ono’s option exercise decision for itolizumab

Itolizumab continues to show clinically meaningful response in highly proteinuric subjects

More than 80% of subjects achieved >50% reduction in urine protein creatinine ratio (UPCR)

Itolizumab demonstrated a favorable safety and tolerability profile

Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company focused on developing novel therapeutics to treat severe autoimmune and inflammatory disorders, today announced positive topline data from the Type B portion of the Phase 1b EQUALISE study evaluating itolizumab in lupus nephritis patients. The data suggests high complete and partial response rates with rapid and deep reduction in urine protein creatinine ratio (UPCR) when itolizumab was added to mycophenolate mofetil/mycophenolic acid (MMF/MPA) and corticosteroids. The topline data delivered to our partner, Ono Pharmaceutical, represents the first of two data set triggers leading to their decision as to whether to exercise their option to acquire itolizumab, which is expected in the second half of 2024.

“Physicians want to rapidly and safely reduce the levels of proteinuria in patients with lupus nephritis, as this has been associated with improved long-term outcomes, so it is important that we saw both early and large reductions in proteinuria in this study,” said Dr. Maple Fung, chief medical officer at Equillium. “The high complete and partial response rates compare favorably to those observed in the registrational studies of voclosporin, which demonstrated an overall response rate of seventy percent at six and twelve months in the active treatment groups. These itolizumab results occurred in the setting of patients tapering their systemic corticosteroids, maintaining stable kidney function, or eGFR, and increasing serum albumin while on study.”

A total of 17 subjects were enrolled in the study, with 16 subjects analyzed as completing through Week 36 (12 weeks following the final dose, or their end of study (EOS) visit). Based on published guidelines for the management of lupus nephritis from the European League Against Rheumatism (EULAR) and European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), clinical activity assessments in this study are focused on the change in UPCR from baseline; proportion of apLN subjects with a complete response (CR), defined as 50% or greater reduction in UPCR and less than 0.5-0.7 g/g; and proportion of subjects achieving a partial response (PR), defined as 50% or greater reduction in UPCR.

Key topline data from the Type B portion of the EQUALISE study in lupus nephritis:

• Subjects were highly proteinuric: baseline mean UPCR of 4.9 g/g.
• Percent reduction from baseline in median spot UPCR is ~73%.
• Best clinical response observed by week 36 or their EOS visit:
  • 6 of 16 (37.5%) subjects achieved CR (UPCR < 0.7 g/g)
  • Additional 7 of 16 (43.8%) subjects achieved PR (UPCR > 50% reduction)
• There was a greater overall response rate (ORR) achieved in patients receiving itolizumab by 12 and 28 weeks than expected compared to the ORR in patients receiving standard of care alone using data generated from the Accelerating Medicines Partnership® (AMP) Lupus Network. Results are comparable to those observed in the Phase 3 AURORA1 study of voclosporin (ORR 70% at 6 and 12 months in active treatment).
• Consistent with the decline in UPCR overtime, subjects were able to taper their systemic corticosteroids over the course of the study with >80% reduction by Week 24.
• Itolizumab induced consistent pharmacodynamic responses in patients reducing the levels of cell surface CD6 on T cells, which is known to reduce T cell activity.
• Itolizumab treatment (over 6 months) was also associated with reductions in absolute lymphocyte counts (ALC), another known pharmacodynamic effect.
• As noted in other studies of drugs whose mechanism leads to reductions in ALC, such as the S1P modulators, the reduction in ALC observed here was not associated with increased rates of infection or other adverse clinical signals.
• The majority of TEAEs were assessed as mild (Grade 1) or moderate (Grade 2) in severity, with the two most common TEAEs being lymphopenia and peripheral edema. Two subjects had at least one serious adverse event, none of which were related to study treatment.

About Systemic Lupus Erythematosus (SLE) & Lupus Nephritis (LN)

SLE is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. LN is a serious complication of SLE, occurring in approximately 30% – 60% of individuals with SLE. LN involves the body’s own immune system attacking the kidneys, causing inflammation and significantly reducing kidney function over time. LN is associated with an increase in mortality compared with the general population and may lead to end-stage renal disease.

About the EQUALISE Study

The EQUALISE study was a two-part Phase 1b open-label proof-of-concept study of itolizumab in patients with SLE and LN. The Type A portion of the study was a multiple ascending-dose clinical study evaluating the safety and tolerability of subcutaneous delivery of itolizumab over a two-week treatment period in 35 patients with SLE. The Type B portion of the study evaluated the safety, tolerability and clinical activity of subcutaneous delivery of itolizumab dosed at 1.6 mg/kg every two weeks over a 24-week treatment period, with follow up out to 36 weeks, in patients with active proliferative LN. Patients in the Type B portion of the study must have presented with greater than 1 gram of proteinuria and had a recent kidney biopsy showing ISN/RPS class III or IV apLN to be eligible for the study. Consistent with standard of care, patients on study also received 2-3 g/day of mycophenolate mofetil/mycophenolic acid (MMF/MPA), and patients may have received pulse systemic corticosteroids that were rapidly tapered.

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 www.equilliumbio.com.

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 the expected timeline for Ono Pharmaceutical to make its decision regarding exercising its option; plans for developing EQ101, EQ302 and itolizumab; 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240401373328/en/