On December 9, 2024 Electra Therapeutics, Inc., a clinical stage biotechnology company developing antibody therapies against novel targets for immunological diseases and cancer, reported the presentation of positive results from the completed Phase 1b study of ELA026 for the treatment of secondary hemophagocytic lymphohistiocytosis (sHLH) (Press release, Electra Therapeutics, DEC 9, 2024, View Source [SID1234648897]). ELA026 is a first-in-class monoclonal antibody that targets SIRP-α/β1/γ on the cell surface of myeloid cells and T lymphocytes, the principal pathological immune cells that induce the cytokine storm and hyperinflammation in sHLH. Targeting SIRP to selectively deplete pathogenic immune cells has potential for broad therapeutic applications in immunology, inflammation and cancer. The results of the ELA026 study in sHLH are being presented today at 2:45 PM PST in an oral session at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, CA.

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The Phase 1b study was an open-label, single-arm, multicenter study designed to evaluate the safety and efficacy of ELA026, assess the pharmacodynamic (PD) and pharmacokinetic (PK) profile, and identify a dose regimen for further evaluation in a Phase 2/3 study (NCT05416307). The Phase 1b study demonstrated that for sHLH patients with the poorest prognosis, those with malignancy-associated HLH (mHLH), treatment with ELA026 in frontline settings achieved 100% overall response rate by week 4 and 100% hospital discharge, as well as 92% survival at two months. Various PD and HLH-related biomarkers showed that ELA026 rapidly attenuated inflammation, which correlated with clinical responses.

"ELA026 has shown potential to be a transformative treatment for sHLH, a life-threatening disease with no approved therapies. Compared with available treatment, which may include chemotherapy and single cytokine-directed therapies, ELA026 may offer a safer, more effective approach to address the overwhelming immune reaction in sHLH. The Phase 1b study results showing rapid PD and biomarker effects and improved survival at two months are particularly promising," said Swaminathan P. Iyer, MD, Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. "There is a growing appreciation that controlling the cytokine storm early in the sHLH disease course is necessary to prevent multiorgan failure and allow for proper treatment of the underlying cancer. It is clear that overcoming this critical early period of hyperinflammation in sHLH provide significant clinical benefits for patients."

"We are highly encouraged by these compelling results for sHLH patients, and Electra is working to advance ELA026 into a pivotal study as rapidly as possible. Through rigor and resolve, our team has pioneered a drug development program targeting SIRP, going from a novel idea to pivotal study readiness in five years," said Kathy Dong, PharmD, MBA, President and CEO of Electra Therapeutics. "We have demonstrated the therapeutic value of selectively depleting pathological immune cells to modulate inflammation and look forward to applying this novel approach with ELA026 and our pipeline to expand to other diseases with high unmet need."

Phase 1b Study Results Presented in Oral Session at ASH (Free ASH Whitepaper)
The oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting, entitled "ELA026, a monoclonal antibody targeting signal regulatory protein-α/β1/γ, rapidly controls inflammation and improves 2-month survival in treatment-naïve malignancy-associated hemophagocytic lymphohistiocytosis," is being presented by the lead author, Abhishek Maiti, MD, Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. This presentation was featured in the section "Granulocytes, Monocytes, and Macrophages: From Inflammation to Hemophagocytic Lymphohistiocytosis." The clinical results presented for ELA026 described the analysis of 12 mHLH patients treated in frontline settings in the completed Phase 1b clinical study. Highlights of the Phase 1b results are as follows:

ELA026 was well tolerated with manageable adverse events.
ELA026 demonstrated rapid PD effects on monocytes and lymphocytes, followed by reduction of markers of inflammation, including ferritin, sCD25, and C‑reactive protein (CRP).
mHLH patients receiving ELA026 in frontline settings achieved treatment outcomes that surpass those observed with available therapies (existing treatments used in the absence of an approved therapy for sHLH):
– 100% overall response rate (12 of 12) ~40% with available therapies.1

– 100% hospital discharge alive (11 of 11, 1 patient withdrew from study before evaluation of this endpoint) inpatient mortality of 20-30% with available therapies.2

– 92% survival at Day 60 (11 of 12) ~50% with available therapies.3

"Because sHLH is a complex, rapidly progressing disease with limited development precedents, advancing ELA026 required a focused approach that our Electra team boldly took on, in collaboration with leading researchers and clinicians. It is gratifying to see the positive Phase 1b results for ELA026 and the potential to improve outcomes for sHLH patients who face this life-threatening condition," said Kim‑Hien Dao, DO, PhD, Chief Medical Officer at Electra. "We have a clear path forward based on recent alignment with the US FDA on the pivotal study design and are moving towards initiating a global Phase 2/3 study in 2025 to address the significant disease burden in sHLH."

About Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare, life-threatening hyperinflammatory disease for which there is no approved treatment. It can be triggered by cancer, infection, autoimmune disease, or immunotherapy. sHLH is associated with a severe inflammatory response for which patients require immediate intervention. Without treatment, patients may experience multiorgan failure and death. sHLH is associated with high mortality early in the disease course, with malignancy-associated HLH (mHLH) patients having a mortality rate of approximately 50% at two months with available therapies.