Equillium Announces Results of the Phase 3 EQUATOR Study of Itolizumab in First-Line Treatment of Patients with Acute Graft-Versus-Host Disease

Rhea-AI Summary

Equillium (Nasdaq: EQ) announced topline data from its Phase 3 EQUATOR study evaluating itolizumab for first-line treatment of acute graft-versus-host disease (aGVHD). While the study did not show improvement in complete response (CR) or overall response rate (ORR) at Day 29, it achieved statistical significance in key longer-term outcomes.

Key findings include:

• Duration of CR: 336 days vs. 72 days (p=0.017)
• Failure-free survival: 154 vs. 70 days (p=0.043)
• Complete response at Day 99: 44.9% vs. 28.6% (p=0.035)
• Positive trend in overall survival with mortality of 24.4% vs. 32.5%

Itolizumab demonstrated a favorable safety profile without increasing infection or sepsis risks. The company has submitted for Breakthrough Therapy designation and expects FDA feedback in May 2025. If positive, they plan to submit a biologics license application in H1 2026.

Positive

• Significant improvement in duration of complete response (336 vs 72 days, p=0.017)
• Better failure-free survival (154 vs 70 days, p=0.043)
• Higher complete response rate at Day 99 (44.9% vs 28.6%, p=0.035)
• Favorable safety profile without increased infection risks
• Lower mortality rate (24.4% vs 32.5%)

Negative

• Failed to meet primary endpoint of Day 29 complete response
• Did not achieve meaningful difference in overall response rate at Day 29
• Potential delay in commercialization pending FDA feedback and approval process

Insights

Clinical Trial Analyst

Equillium's Phase 3 EQUATOR trial results present a mixed clinical picture with significant regulatory implications. The study's failure to meet its primary endpoint of improved complete response (CR) or overall response rate (ORR) at Day 29 represents a substantial setback. However, the statistically significant longer-term outcomes provide meaningful counterbalance:

The data shows compelling longer-term benefits with median duration of complete response at 336 days vs 72 days (367% improvement, p=0.017), failure-free survival of 154 vs 70 days (120% improvement, p=0.043), and Day 99 complete response rate of 44.9% vs 28.6% (p=0.035).

These results create a complex regulatory scenario. While primary endpoints typically drive approval decisions, the FDA has shown flexibility for rare diseases with high mortality and treatment options. First-line aGVHD represents exactly such a case with no approved therapies and one-year mortality exceeding 40%.

The regulatory pathway now hinges on the FDA's feedback expected in May 2025. Equillium's regulatory strategy leverages the existing Orphan Drug and Fast Track designations, with new applications for Breakthrough Therapy designation. The company's timeline for a potential BLA submission in H1 2026 depends entirely on this upcoming FDA interaction.

The favorable safety profile, particularly the lack of increased infection or sepsis risk (key mortality drivers in aGVHD), strengthens the benefit-risk profile despite missing the primary endpoint.

Treatment with itolizumab did not improve complete or overall response rates at Day 29

Itolizumab achieved statistical significance in multiple secondary endpoints demonstrating compelling clinical benefit in longer-term outcomes, including complete response at Day 99, duration of complete response and failure-free survival

Breakthrough Therapy designation and meeting requests to discuss potential for Accelerated Approval submitted to FDA, feedback expected during May 2025

Management will host a conference call and webcast today at 8:30 am ET

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 topline data from the Phase 3 EQUATOR study evaluating itolizumab in first-line treatment of patients with acute graft-versus-host disease (aGVHD). The study results did not demonstrate a meaningful difference in complete response (CR) or overall response rate (ORR) at Day 29 between patients treated with itolizumab and placebo; however, statistically significant and clinically meaningful benefit in longer-term outcomes were achieved, including complete response at Day 99, duration of complete response and failure-free survival. Itolizumab exhibited a favorable safety and tolerability profile and did not increase the risk of clinical sequelae, including infection or sepsis, primary drivers of the high mortality associated with aGVHD.

“While we did not observe improvements in Day 29 outcomes, itolizumab demonstrated compelling clinical results in several important longer-term outcomes, conferring potential patient benefit where there are no approved therapies,” said Bruce Steel, chief executive officer at Equillium. “Based on these data and prior FDA guidance, we have filed for Breakthrough Therapy designation and have been granted a meeting to discuss the potential for Accelerated Approval of itolizumab for first-line treatment of aGVHD, a rare disease where one-year mortality exceeds 40 percent and itolizumab has already received Orphan Drug and Fast Track designations. We expect feedback from the FDA during May and, if positive, we would plan to submit a biologics license application during the first half of 2026.”

“The longer-term outcomes are important,” said Dr. John Koreth, Professor of Medicine, Dana-Farber Cancer Institute, Harvard Medical School. “There are no approvals in first-line therapy for aGVHD, and no drug candidates have been able to demonstrate efficacy beyond four weeks. To demonstrate statistical significance in pre-specified endpoints of duration of complete response and failure-free survival, compared to standard of care therapy, is clinically meaningful.”

The Phase 3 EQUATOR study in first-line aGVHD demonstrated a favorable safety and tolerability profile, and clinically meaningful longer-term outcomes. There was no meaningful difference in CR or ORR, the primary endpoint and a key secondary endpoint of the study (respectively), at Day 29 between patients treated with itolizumab and placebo, but statistical significance was achieved in several critically important secondary endpoints demonstrating improvement in longer term outcomes:

• Statistical significance in duration of CR favoring itolizumab, with a median 336 days vs. 72 days, p-value 0.017.
• Statistical significance in failure-free survival favoring itolizumab, with a median 154 vs. 70 days, p-value 0.043.
• Statistical significance in complete response at Day 99 favoring itolizumab, with 35 (44.9%) vs. 22 (28.6%) patients, p-value 0.035.
• Positive trend in overall survival favoring itolizumab, with mortality of 19 (24.4%) vs. 25 (32.5%) patients.
• Steroid tapering and rates of primary disease relapse and chronic GVHD were similar for both treatment arms.

Summary of Efficacy Results from the EQUATOR Study
Endpoint, n (%)	Itolizumab ITT (N=79) mITT (N=78)	Placebo ITT (N=79) mITT (N=77)	p-value
CR at Day 29 (ITT), n (%) (Primary Endpoint)	34 (43.0)	38 (48.1)	NSS
ORR at Day 29 (ITT), n (%) (Key Secondary Endpoint)	49 (62.0) VGPR = 8 (10.1) PR = 7 (8.9)	43 (54.4) VGPR = 1 (1.3) PR = 4 (5.1)	NSS
Durable CR at Day 99 (ITT)#, n (%) (Key Secondary Endpoint)	23 (29.1)	13 (16.5)	NSS
Durable CR at Day 99 (of Day 29 CRs) (ITT)#*, n (%)	23 (67.6)	13 (34.2)	0.005
CR at Day 99 (mITT)*, n (%)	35 (44.9)	22 (28.6)	0.035
Duration of CR (mITT), median days	336 days	72 days	0.017
Failure Free Survival (mITT)
Kaplan-Meier estimate of rate at Day 365, % Median days	39.5% 154 days	22.9% 70 days	0.043
Overall Survival (mITT)
Kaplan-Meier estimate of rate at Day 365, % Deaths, n	66.7% 19	49.6% 25	NSS
Data based on 11 December 2024 database lock, unless otherwise noted, and subject to change. #Estimate as of 12 February 2025 with one subject pending final analysis; *Post-hoc analysis. Analyses were pre-specified in the Statistical Analysis Plan, unless indicated as a post-hoc analysis. Abbreviations: ITT, intent-to-treat; mITT, modified intent-to-treat (subjects who received at least one dose; removes three patients that did not receive any study treatment); CR, complete response; NSS, not statistically significant; VGPR, very good partial response; PR, partial response

The safety profile observed in the EQUATOR study was consistent with that observed in previously reported studies of itolizumab, and itolizumab did not increase the risk of clinical sequelae, including rates of infection and sepsis.

Overall Summary of Treatment-Emergent Adverse Events (Safety Population / mITT)
Event, n (%)	Itolizumab N=78	Placebo N=77	Total N=155
Subjects with any TEAE	77 (98.7)	74 (96.1)	151 (97.4)
Subjects with TEAE leading to study drug discontinuation	10 (12.8)	3 (3.9)	13 (8.4)
Subjects with TESAEs	45 (57.7)	47 (61.0)	92 (59.4)
Infections and infestations TESAEs	22 (28.2)	29 (37.7)	51 (32.9)
Treatment-related TESAEs	5 (6.4)	3 (3.9)	8 (5.2)
Subjects with TEAE leading to death	18 (23.1)	25 (32.5)	43 (27.7)
Treatment-related TEAE leading to death	0 (0)	0 (0)	0 (0)
Most Common TESAEs
Sepsis	4 (5.1)	14 (18.2)	18 (11.6)
Respiratory failure	3 (3.8)	4 (5.2)	7 (4.5)
Pneumonia	3 (3.8)	3 (3.9)	6 (3.9)
Septic shock	2 (2.6)	4 (5.2)	6 (3.9)
Data based on 11 December 2024 database lock, unless otherwise noted, and subject to change. Abbreviations: mITT, modified intent-to-treat (subjects who received at least one dose; removes three patients from ITT that did not receive any study treatment); TEAE, treatment-emergent adverse event; TESAE treatment-emergent serious adverse event

Webcast and Conference Call

Management will host a conference call accompanied by a slide presentation to provide an overview of the data from the Phase 3 EQUATOR study in first-line aGVHD, for analysts and institutional investors, at 8:30 am ET today, March 27, 2025. To access the call, please dial (800) 715-9871 or (646) 307-1963 for international callers, and if needed provide conference ID number 2574379. A live webcast of the call will also be available on the company’s Investor Relations page. The webcast will be archived for 180 days.

About Graft-Versus-Host Disease (GVHD)

GVHD is a multisystem disorder that is a common complication of allogeneic hematopoietic stem cell transplants (allo-HSCT) caused by the transplanted immune system recognizing and attacking the recipient’s body. Symptoms of GVHD include rash, itching, skin discoloration, nausea, vomiting, diarrhea, and jaundice, as well as eye dryness and irritation.

GVHD is the leading cause of non-relapse mortality in cancer patients receiving allo-HSCT, and its risk limits the number and type of patients receiving HSCT. GVHD results in high morbidity and mortality, with one year survival as low as 40%. There are no approved treatments for first-line aGVHD.

About the EQUATOR Study

The Phase 3, randomized, double-blind, placebo-controlled multicenter study (NCT05263999) compared the efficacy and safety of intravenous administered itolizumab versus placebo (randomized 1:1) as a first-line therapy in 158 adult and adolescent patients with Grade III-IV aGVHD, or Grade II aGVHD with lower gastrointestinal involvement, in combination with high doses of corticosteroids, the current standard of care. The primary study endpoint was complete response rate (CR) at Day 29; key secondary endpoints included overall response rate (ORR) at Day 29 and rate of durable CR from Day 29 through Day 99. Additional secondary outcomes included CR at Day 99, duration of CR, failure free survival, and overall survival.

Per the study protocol, patients received 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. Subjects received 2 mg/kg methylprednisolone or equivalent on Day 1 and were randomized in a 1:1 ratio to the following two treatment groups:

1. 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 (79 subjects)
2. Group B: Placebo, 7 doses every other week, plus systemic corticosteroids (79 subjects)

The EQUATOR study remains ongoing with all patients having completed dosing, and 30 patients in the follow-up period per protocol. An independent data monitoring committee oversees the study and regularly reviews safety data.

About Itolizumab

Itolizumab is a clinical-stage, first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to 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 several novel immunomodulatory assets and product platform targeting immuno-inflammatory pathways.

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”, “potential” 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 and strategies with respect to developing itolizumab (EQ001), the encouraging impact of the positive data in the context of Equillium’s Phase 3 EQUATOR study in aGVHD, Equillium’s ability to raise additional capital to support filing of a biologics license application, the expected timing of FDA feedback, 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; Equillium’s ability to continue as a going concern; 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; whether the topline results from the EQUATOR study will support accelerated approval and Breakthrough Therapy designation; changes in the competitive landscape; Equillium’s ability to raise additional funding; and changes in Equillium’s strategic plans. 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.

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Corporate Contact

Michael Moore

Vice President, Investor Relations & Corporate Communications

619-302-4431

ir@equilliumbio.com

Source: Equillium, Inc.

FAQ

What were the key results of Equillium's (EQ) Phase 3 EQUATOR trial for itolizumab?

The trial showed significant improvements in longer-term outcomes, including 336 vs 72 days duration of complete response (p=0.017), but did not meet primary endpoint of Day 29 complete response.

When does Equillium (EQ) expect FDA feedback on itolizumab's Breakthrough Therapy designation?

Equillium expects FDA feedback during May 2025.

What is the timeline for Equillium's (EQ) biologics license application for itolizumab?

If FDA feedback is positive, Equillium plans to submit the biologics license application during the first half of 2026.

How did itolizumab affect survival rates in Equillium's (EQ) Phase 3 EQUATOR trial?

The trial showed a positive trend in overall survival, with mortality rates of 24.4% in the itolizumab group versus 32.5% in the control group.

What was the safety profile of Equillium's (EQ) itolizumab in the Phase 3 trial?

Itolizumab demonstrated a favorable safety profile and did not increase the risk of clinical complications, including infection and sepsis rates.