24 May 2022 - - US-based biotechnology company Salubris Biotherapeutics, Inc has reported new data from Cohort 2 of the ongoing Phase 1 study evaluating JK07, the company's lead drug candidate, for the treatment of heart failure with reduced ejection fraction (HFrEF), the company said.

The company also announced the submission of the first clinical trial application in Europe for its lead oncology program, JK08, and the appointment of Arian Pano, M.D., as Chief Medical officer.

The new Cohort 2 Data for JK07 shows favorable safety and further promising activity in patients with HFrEF.

In this ongoing randomized, double-blind, placebo-controlled, dose-escalation Phase 1b study evaluating JK07, patients treated in Cohort 2 demonstrated a favorable safety profile and encouraging signals of clinical activity.

In addition, dose-dependent increases in biomarker surrogates of target engagement have been observed across the two completed cohorts.

Enrollment in Cohort 3, of five planned cohorts, has commenced in this Phase 1b study and SalubrisBio plans to report additional data from this study at future medical meetings.

The first CTA has been filed in Europe seeking approval to initiate a Phase 1/2 study evaluating JK08 monotherapy for the treatment of advanced solid tumors.

JK08 augments the T-regulatory cell targeting of a CTLA-4-specific antibody with an IL-15/sushi domain fusion peptide, which locally induces NK cell activation and antibody-dependent cellular cytotoxicity, two biological hallmarks predictive of response to CTLA-4 targeted therapy.

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.

Upon obtaining regulatory approvals, the company plans to initiate recruitment during 3Q22.

Dr. Pano comes to SalubrisBio from Kiniksa Pharmaceuticals, where he served as SVP of Clinical Development, overseeing all functional groups, including medical, research, clinical operations, regulatory, safety, biometrics, and medical writing.

Previously he served as SVP of Clinical Development for Galapagos NV, and concurrently served as the US country head and Global Head of Safety.

Dr. Pano has an extensive background in research and development with a focus on cardiovascular, metabolic rare diseases, inflammation and fibrosis. He earned his MD degree from the University of Tirana, Albania, completing fellowships in invasive cardiology and pediatrics.

In addition, he holds an MPH in Healthcare Management from Harvard's School of Public Health.

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 and undesirable side effects.

Research has shown that NRG-1 induces signaling through interaction with two different receptors HER3 and HER4.

The HER4 pathway appears to be responsible for the regenerative effects in the heart, while the HER3 pathway appears primarily responsible for safety and tolerability limitations of recombinant NRG-1.

By blocking HER3 signaling with an antibody fusion design, JK07 selectively stimulates the HER4 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 an IL-15 fusion domain.

The JK08 design builds upon a breadth of clinical studies with CTLA-4 antibodies and recombinant IL-15 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 exhibited potent stimulation of NK cell expansion and enhancement of ADCC in pre-clinical and clinical studies.

Through the incorporation of a CTLA-4 antibody and IL-15 into a single molecule, JK08 can channel the potent immune stimulation of IL-15 through the CTLA-4 antibody domain towards depletion of T-regulatory cells and targeted reversal of 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.