Alzumab (itolizumab) / Biocon, Center of Molecular Immunology, Equillium, Ono Pharma - LARVOL DELTA

Equillium Announces Feedback from the U.S. Food and Drug Administration (Businesswire) - "Equillium, Inc...today announced that the company has received feedback from its Type D meeting with the U.S. Food and Drug Administration (FDA) to discuss the regulatory pathway for Accelerated Approval, as well as the company’s filing for Breakthrough Therapy designation for itolizumab for first-line treatment of acute graft-versus-host disease (aGVHD)....The FDA declined to grant Breakthrough Therapy designation or support an Accelerated Approval pathway based on the EQUATOR study data. The FDA highlighted its attention to achieving response outcomes at Day 29, per existing FDA guidance; however, the FDA did indicate openness to evaluating other endpoints, including longer term outcomes, provided independent data supports the validity of such endpoints."

FDA event • Acute Graft versus Host Disease

EQUIP: A Study of Itolizumab (EQ001) to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity in Uncontrolled Asthma (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Equillium | Phase classification: P1b ➔ P1

Phase classification • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

EQUATE: A Study to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity of EQ001 in Subjects With aGVHD (clinicaltrials.gov) - P1/2 | N=30 | Completed | Sponsor: Equillium | Phase classification: P1b/2 ➔ P1/2

Phase classification • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Equillium Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Corporate and Clinical Highlights (Businesswire) - "'This morning...we announced topline data from the Phase 3 EQUATOR study evaluating itolizumab in first-line treatment of acute graft-versus-host disease...Based on these data and prior FDA guidance, we have submitted a request for Breakthrough Therapy designation and have been granted a meeting with the FDA to discuss the potential for Accelerated Approval of itolizumab for first-line treatment of aGVHD, an indication where itolizumab has already received Orphan Drug and Fast Track designations. We expect feedback from the FDA during May 2025 and, if positive, subject to raising additional capital, we would plan to submit a biologics license application during the first half of 2026....Revenue for the fourth quarter of 2024 was $4.4 million, compared with $9.2 million for the same period in 2023. For the full year of 2024, revenue was $41.1 million, compared with $36.1 million for the full year of 2023."

Commercial • FDA event • FDA filing • Acute Graft versus Host Disease

Itolizumab regulates activating and inhibitory signals on effector cells, improving their cytotoxicity against CD318+ tumor cell lines (Frontiers) - "Blockade of the CD6-CD318 interaction by itolizumab enhances the cytotoxic capacity of CD8 and NK T cells against CD318+ tumor lines, reverses the NKG2A/NKG2D ratio and increases granzyme B and IFNγ production. Itolizumab also modulates immune responses by downregulating CD5 expression and upregulating the inhibitory receptors PD-1 and CTLA-4 on lymphocytes, which helps to reduce exacerbated responses. It also enhances CD318+ tumor cell killing when combined with other immune checkpoint inhibitors. In addition, we report that the CD6-CD318 interaction inhibits proliferation and survival while downregulating CD6 expression on lymphocytes both in vitro and in human breast cancer tissue samples. This finding reinforces the significance of the CD6-CD318 axis as an immune checkpoint, thus highlighting the potential of itolizumab as an immune checkpoint inhibitor."

Preclinical • Solid Tumor

Equillium Announces Results of the Phase 3 EQUATOR Study of Itolizumab in First-Line Treatment of Patients with Acute Graft-Versus-Host Disease (Businesswire) - P3 | N=200 | EQUATOR (NCT05263999) | Sponsor: Equillium | "Equillium...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....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."

P3 data • Acute Graft versus Host Disease

A Study of Itolizumab in Combination With Corticosteroids for the First-Line Treatment of Acute Graft Versus Host Disease (EQUATOR) (clinicaltrials.gov) - P3 | N=200 | Active, not recruiting | Sponsor: Equillium | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2024 ➔ Oct 2025

Enrollment closed • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Equillium Announces Positive Data from Phase 2 Study Evaluating Itolizumab in Patients with Moderate to Severe Ulcerative Colitis (Businesswire) - P2 | N=NA | "Baseline disease severity of the study was greater in the itolizumab arm, where 23% of patients were classified as severe (Total Mayo Score of 11) versus 0% in the placebo and adalimumab arms, and 66% had left-sided colitis versus 30% and 43% in the placebo and adalimumab arms, respectively. Additional data is expected to be presented at a future scientific conference during 2025. 23.3% clinical remission in the itolizumab arm at 12 weeks (primary endpoint) vs. 20.0% in adalimumab vs. 10.0% in placebo; 63.3% clinical response in the itolizumab arm at 12 weeks vs. 60.0% in adalimumab vs. 46.7% in placebo; 16.7% endoscopic remission in the itolizumab arm at 12 weeks vs. 16.7% in adalimumab vs. 6.7% in placebo; Itolizumab was generally well tolerated, and no safety signal was observed."

P2 data • Ulcerative Colitis

Corrigendum to: Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study. (PubMed, Acute Crit Care) - No abstract available

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease

Contemporary Updates in the Prevention and Treatment of Graft-Versus-Host Disease. (PubMed, Curr Hematol Malig Rep) - "Clinical trials in preventing GVHD demonstrate lower rates of severe acute GVHD and chronic GVHD with post-transplant cyclophosphamide. For acute GVHD, lower risk acute GVHD appears amenable to steroid-sparing therapies, such as sirolimus and itacitinib. Combinations with novel agents such as itolizumab appear promising for high risk acute GVHD...For chronic GVHD requiring therapy beyond steroids, ruxolitinib, belumosudil, and ibrutinib are now available and should be considered. Increasingly, GVHD has become a manageable complication after allogeneic HCT potentially translating to greater success with allogeneic HCT in the future."

Journal • Review • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation

Equillium Reports Third Quarter 2024 Financial Results and Provides Corporate and Clinical Updates (Businesswire) - Anticipated Upcoming Milestones: Itolizumab: Topline data from Phase 2 study in ulcerative colitis – Q1 2025...Research and development (R&D) expenses for the third quarter of 2024 were $9.6 million, compared to $9.0 million for the same period in 2023. The increase was primarily due to greater expenses associated with chemistry, manufacturing and controls (CMC) activities related to itolizumab..."

Commercial • P2 data • Acute Graft versus Host Disease • Asthma • Graft versus Host Disease • Immunology • Inflammatory Bowel Disease • Systemic Lupus Erythematosus • Ulcerative Colitis

Equillium Maintains Rights to Itolizumab Following Ono Partnership (Businesswire) - "'In addition, in collaboration with Equillium, our partner Biocon has recently completed a robust placebo-controlled Phase 2 study of itolizumab in biologic-naïve patients with moderate to severe ulcerative colitis, and we expect topline data from this study also early in the new year...'"

P2 data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Equillium Maintains Rights to Itolizumab Following Ono Partnership (Businesswire) - "Anticipated Upcoming Milestones: Itolizumab: Topline data from Phase 3 EQUATOR study in aGVHD – potential acceleration to Q1 2025."

P3 data: top line • Acute Graft versus Host Disease

Protein profile following therapy with DMF in patients with plaque psoriasis (ESDR 2024) - "Th1 and Th17 related cytokines secreting cytotoxic type 17 CD8 T cells have been discovered that (Ortega et al 2009), CD5+T cells produce both IL17 and TNFa in psoriasis (Zhou et al 2022) and Itolizumab, targeting distal domain of CD6 has been clinically successful in patients who did not respond to any other therapy (Dogra et al 2020). Genes identified in this proteomics analysis may help us understand the mechanism of action of DMF in psoriasis patients. Grant reference: Almirall."

Clinical • Dermatology • Immunology • Psoriasis • CD5 • CD8 • IL10 • IL17A • IL3 • IL4 • TNFA

A Study of Itolizumab in Combination With Corticosteroids for the First-Line Treatment of Acute Graft Versus Host Disease (EQUATOR) (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Equillium | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Jul 2024 ➔ Dec 2024

Combination therapy • Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Equillium Reports Second Quarter 2024 Financial Results and Provides Recent Corporate and Clinical Highlights (Businesswire) - P2 | N=36 | NCT05589610 | Sponsor: Equillium | "Announced positive topline data from Phase 2 study of EQ101 in alopecia areata subjects, including 29% of completed subjects with moderate to severe disease achieving SALT (Severity Alopecia Tool) ≤ 20....Anticipated Upcoming Milestones: EQ101: Transition to subcutaneous delivery and initiate Phase 2 dose optimization study in alopecia areata – 2025. EQ302: Initiate Phase 1 study – 2H 2025....Revenue for the second quarter of 2024 was $13.9 million, compared to $9.1 million during the same period in 2023. Revenue in the second quarters of 2024 and 2023 consisted entirely of itolizumab development funding and amortization of the upfront payment resulting from the Asset Purchase Agreement with Ono.

Commercial • New P2 trial • P2 data • Acute Graft versus Host Disease • Alopecia • Immunology

Equillium Announces Positive Interim Analysis from Phase 3 EQUATOR Study of Itolizumab in Acute Graft-Versus-Host Disease (Businesswire) - "Equillium, Inc...announced a positive recommendation from the Independent Data Monitoring Committee (IDMC) based on its review of the interim results from the Phase 3 EQUATOR study evaluating itolizumab in subjects with acute graft-versus-host disease (aGVHD). The IDMC reviewed unblinded data on over 100 patients through Day 29 of treatment from the study, with pre-determined futility and efficacy stopping boundaries, and recommended that the study proceed with continued enrollment, without modifications."

DSMB • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Long-term therapy with itolizumab is safe and effective for patients with moderate to severe psoriasis: Results from an expanded-access program. (PubMed, Int Immunopharmacol) - "The observed effects were dose-dependent, with 1.6 mg/kg being the most convenient dose. This study further supports the strategy of targeting the CD6-ALCAM signaling pathway for the treatment of psoriasis and the use of itolizumab as a valuable asset in the armamentarium of anti-psoriasis drugs."

Journal • Dermatology • Immunology • Psoriasis

Equillium Announces Interim Enrollment Achieved in Phase 3 EQUATOR Study of Itolizumab in Acute Graft-Versus-Host Disease (Businesswire) - "Equillium...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....'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....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."

Commercial • Enrollment status • P3 data • Acute Graft versus Host Disease

Equillium Reports First Quarter 2024 Financial Results and Provides Recent Clinical Highlights (Businesswire) - "If Ono exercises their option to acquire our rights to itolizumab we would receive an exercise payment of approximately $321 million, which would significantly extend our cash runway beyond the second half of 2025 - our current guidance - and we would remain eligible to receive approximately $101 million in additional milestone payments....Revenue for the first quarter of 2024 was $10.7 million, compared to $8.9 million during the same period in 2023. Revenue in the first quarters of 2024 and 2023 consisted entirely of itolizumab development funding and amortization of the upfront payment resulting from the Asset Purchase Agreement with Ono.”"

Commercial • Acute Graft versus Host Disease • Lupus Nephritis

Surface CD6 regulates T cell adhesion and migration through direct ligand interaction and stabilization of VLA4. (IMMUNOLOGY 2024) - "To investigate its role in adhesion and transendothelial migration, we used itolizumab, an anti-CD6 mAb that can induce cleavage of CD6 from the T cell surface when in the presence of monocytes...Modulating CD6 on T cells or blocking ALCAM on the HUVEC also translated to a ~3-fold decrease in migration of Teff cells.Loss of CD6 was associated with reduced protein levels of VLA4, but not of other integrins, under both stimulated (~70%) and non-stimulated conditions (~40%). Antibody blockade of CD6 without cleavage did not affect VLA4 levels, but still decreased migration of unstimulated T cells though less so than in stimulated T cells, where VLA4 reduction is required to modulate migration.Our data demonstrate that CD6 contributes to cell adhesion/migration both through direct ligand interactions with ALCAM, and through the stabilization of cell membrane VLA4 and that these functions can be abrogated by modulation of cell surface levels of CD6."

Inflammation

Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study. (PubMed, Acute Crit Care) - "The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19."

Journal • Retrospective data • Critical care • Infectious Disease • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • IFNG • IL6

Equillium Announces Positive Topline Data from the Type B Portion of the Phase 1b EQUALISE Study of Itolizumab in Lupus Nephritis (Businesswire) - P1b | N=55 | EQUALISE (NCT04128579) | Sponsor: Equillium | "Equillium...today announced positive topline data from the Type B portion of the Phase 1b EQUALISE study evaluating itolizumab in lupus nephritis patients....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....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 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."

P1 data • Lupus Nephritis

Equillium Reports on Fourth Quarter and Full Year 2023 Financial Results and Corporate and Clinical Highlights (Businesswire) - "Anticipated Upcoming Milestones: (i) EQ101: Phase 2 clinical study in subjects with moderate to severe alopecia areata - topline data anticipated in Q2 2024; (ii) Itolizumab: EQUALISE lupus nephritis topline data to Ono anticipated in the coming weeks; EQUATOR acute graft-versus-host disease interim review anticipated in Q3 2024."

P1 data • P2 data • P3 data • Acute Graft versus Host Disease • Alopecia • Lupus Nephritis

A Study of Itolizumab in Combination With Corticosteroids for the First-Line Treatment of Acute Graft Versus Host Disease (EQUATOR) (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Equillium | Trial completion date: Nov 2024 ➔ Jul 2025 | Trial primary completion date: Dec 2023 ➔ Jul 2024

Combination therapy • Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology