Salubris Biotherapeutics Announces Updated Phase 1b Data Demonstrating that JK07, the First Investigational Antibody Fusion Protein for Heart Failure, Resulted in Clinically Meaningful Improvements in Ejection Fraction
– Completed Second Cohort Showed an Average 30% Relative Increase in Ejection Fraction (EF) at 90 Days Following a Single Administration of JK07 –
– Cohort 3 Sentinel Subject Demonstrated a >70% Relative EF Increase at Day 30 –
– Company also Announces the First CTA Approval for JK08, the First Investigational IL15-CTLA4 Antibody Fusion for Solid Tumors –
Gaithersburg, MD – September 7, 2022 – Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced positive interim data from the ongoing Phase 1b study of JK07 in heart failure with reduced ejection fraction (HFrEF). The interim data includes eleven NYHA II/III subjects across three single-ascending dose cohorts. Single doses were administered intravenously and changes from baseline values of left ventricular EF were measured for each patient. Following completion of enrollment in the first two cohorts, administration of JK07 led to dose-dependent improvements in EF, with an average improvement of 30% observed at day (D) 90 in Cohort 2. The unblinded sentinel subject in Cohort 3 has shown a 70% improvement from baseline at D30.
“JK07’s antibody-fusion design is demonstrating its potential to deliver the durable therapeutic effect of neuregulin, without the associated toxicity, to regenerate heart function and restore quality of life for heart failure patients”, said Sam Murphy, Chief Executive Officer of SalubrisBio. “The consistent, dose-dependent trends we’re observing in EF following a single dose, in conjunction with a favorable safety profile and concordant changes in established biomarkers, are highly encouraging and we look forward to further results from our third cohort and beyond. We are also excited to now be recruiting for the first clinical trial with our IL15-CTLA4 antibody fusion, JK08, and we expect to share initial data in 2023.”
Summary of JK07 Data
At D30, Cohorts 1 (dose: 0.03 mg/kg) and 2 (dose: 0.09 mg/kg) demonstrated similar average improvements in EF, with Cohort 1 (n=4) achieving a 20% improvement and Cohort 2 (n=4) achieving a 19% improvement. Early data from the sentinel subject in Cohort 3 (dose: 0.27 mg/kg) demonstrated a robust response to a single administration of JK07 with a >70% increase in EF at D30 (EF improvement from 22% to 38% absolute). At D90 in the first two cohorts, average EF improvement in Cohort 1 receded to 9% above baseline, while Cohort 2 further increased to 30%. In contrast, placebo subjects (n=2) showed a 4% average improvement in EF at D30 and a decline of 14% on D90. Moreover, dose-dependent increases in biomarker surrogates of target engagement were observed in each JK07-treated subject across the first two cohorts, and again in the sentinel subject in Cohort 3, indicating that target engagement has not yet been saturated. JK07 has been generally well-tolerated in the study, with no serious adverse events (SAEs) reported to date and enrollment of the randomized portion of Cohort 3 ongoing. Detailed findings will be presented at a future medical conference.
The JK07 Cohort 2 EF improvement of 30% at D90 is comparable to a precedent neuregulin study which demonstrated 33% improvement at D90 following single-dose administration[i]. However, in the precedent study, dose limiting toxicities were observed at those same dose levels (0.19 – 1.51 mg/kg, aggregated in analysis)1. JK07 Cohort 3, therefore, represents the potential for new levels of activity not seen before in neuregulin clinical studies.
Initiation of JK08 Clinical Trial in Europe
The Company’s first clinical trial application to begin a Phase 1/2 study of JK08 as a monotherapy treatment for solid tumors in adults has been approved in Europe, and recruiting is now ongoing. The study will assess the safety, pharmacokinetics, and anti-tumor activity of JK08 at multiple dose levels and will include multiple expansion cohorts following selection of the optimal biologic dose.
JK07 is a recombinant fusion protein consisting of a fully human immunoglobulin IgG1 monoclonal antibody and an active polypeptide fragment of the human growth factor neuregulin [NRG-1]. NRG-1 is a clinically validated growth factor that has shown promising activity in HFrEF, but also undesirable side effects. Research has shown that NRG-1 induces signaling through interaction with two different receptors – HER3/ErbB3 and HER4/ErbB4. The HER4/ErbB4 pathway appears to be responsible for the regenerative effects in the heart, while the HER3/ErbB3 pathway appears primarily responsible for safety and tolerability limitations of recombinant NRG-1. By blocking HER3/ErbB3 signaling with an antibody fusion design, JK07 selectively stimulates the HER4/ErbB4 pathway with a favorable pharmacokinetic profile, which has the potential to significantly widen the therapeutic window of NRG-1 and yield better clinical effects.
JK08 is a recombinant fusion protein consisting of a CTLA-4-specific antibody and a C-terminal IL-15/sushi domain. JK08 was designed based on clinical studies from both individual molecules, which together portend synergistic effects in an antibody fusion construct. The CTLA-4-specific antibody ipilimumab validated CTLA-4 as a target for cancer therapy, but response rates are limited. Analysis of clinical samples demonstrated that NK cell activity signatures and ADCC biomarkers correlate with ipilimumab responses. Recombinant IL-15 has demonstrated potent stimulation of NK cell expansion and activation in clinical studies. JK08 channels the potent immune stimulation of IL-15 through the CTLA-4 antibody domain towards T-regulatory cell depletion and reversing immunosuppression which may contribute to cancer progression.
SalubrisBio is a clinical-stage biotechnology company dedicated to discovering and developing complex biologics for cardiovascular, oncology, and neurodegenerative diseases. SalubrisBio was founded in August 2016 as a wholly-owned subsidiary of the China-based pharmaceutical company Shenzhen Salubris Pharmaceuticals Co. Ltd. Headquartered in the US, SalubrisBio reflects Shenzhen Salubris Pharmaceuticals’ commitment to innovation and expansion into the global market and retains the core philosophy of developing therapeutics for large patient populations with significant unmet needs.
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[i] Lenihan et al. A Phase I, Single Ascending Dose Study of Cimaglermin Alfa (Neuregulin 1β3) in Patients With Systolic Dysfunction and Heart Failure. JACC Basic Transl Sci. 2016 Dec 26;1(7):576-586.