Salubris Biotherapeutics, Inc.

JK08 demonstrated robust, dose-dependent pharmacodynamic activity Favorable safety and tolerability pro at dose levels evaluated to date JK08 is an immunocytokine fusion protein designed to synergistically widen the therapeutic windows of validated cancer targets CTLA-4 and IL-15 GAITHERSBURG, Md.--(BUSINESS WIRE)-- Salubris Biotherapeutics Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced that positive initial data from the first-in-human study evaluating JK08 in adults with solid tumors were presented in a poster session during the European Society of Medical Oncology Annual Congress 2023. The presentation included safety data from 32 patients with relapsed or refractory solid tumors who received subcutaneous JK08 monotherapy once weekly in this Phase 1b/2 dose escalation study. At the dose levels evaluated to date, JK08 has been well tolerated, demonstrating preliminary disease stability and anticipated modulation of target immune cell populations in heavily pre-treated patients. Marked induction of NK and CD8+ T cells has been observed, and corresponding activation of these cell populations has been demonstrated through increased HLA-DR expression within these populations. More than 20% of heavily, pre-treated advanced metastatic cancer patients have remained on treatment for 3 months or longer demonstrating preliminary clinical benefit with monotherapy JK08, with the longest continuing therapy for 29 weeks. The most common adverse events have been mild to moderate (Grade 1 & 2) and consist of injection site reactions (ISRs), fatigue, pyrexia, anemia and nausea. No dose limiting toxicities or drug related adverse events leading to treatment discontinuations have been observed to date. “JK08 combines CTLA-4 targeting with the effects of IL-15, with the aim of enhancing anti-tumor immune responses while managing potential side effects,” said Sam Murphy, Chief Executive Officer of SalubrisBio. “We are pleased to see promising, dose-dependent pharmacodynamic activity and a favorable safety and tolerability pro this heavily pre-treated patient population. While early, the data are very encouraging and we look forward to further evaluating JK08’s potential for solid tumor patients.” The ongoing Phase 1b/2, open label, dose escalation and cohort expansion study (NCT05620134) is designed to evaluate the safety and preliminary anti-tumor activity of JK08 in patients with unresectable locally, advanced or metastatic cancer. After dose escalation, monotherapy and combination dose expansion cohorts are planned. SalubrisBio plans to report additional data from this study at future medical meetings. About JK08 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. About SalubrisBio 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.

≥31% Average Improvement in Ejection Fraction (EF) Observed at the Mid and High Dose Levels Full Study Results Show JK07 to be Well Tolerated with No Dose-Limiting Toxicities Observed Company on Track to Initiate Phase 2 Repeat-Dose Study of JK07 in Heart Failure with Reduced Ejection Fraction (HFrEF) and Preserved Ejection Fraction (HFpEF) in H1 2024 GAITHERSBURG, Md.--(BUSINESS WIRE)-- Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced positive updated results from the completed Phase 1b study of JK07 in patients with HFrEF. The data were presented in a late breaking oral session during the Heart Failure Society of America Annual Scientific Meeting 2023. JK07 is the first investigational antibody fusion protein and first selective ErbB4 agonist to enter clinical development for heart failure. Heart failure is a leading cause of morbidity and mortality globally, with estimates of more than 6 million patients affected by HFrEF and HFpEF in the US. “We are highly encouraged by the meaningful improvements in ejection fraction JK07 has demonstrated through 6 months following a single dose,” said Sam Murphy, Chief Executive Officer of SalubrisBio. “The durable and sustained responses observed to date suggest that JK07 has the potential to improve functional capacity, quality of life, and long-term outcomes for these patients, who currently have limited treatment options. We are pleased to be advancing JK07 into a multiple-dose Phase 2 study in both HFrEF and HFpEF to further evaluate its clinical potential in these prevalent heart failure populations.” In the completed Phase 1b study, fourteen patients were randomized 3 to 1 active treatment to placebo (11 JK07 : 3 placebo), with five patients in each of the first two cohorts (0.03mg/kg and 0.09 mg/kg, respectively), and four in the third cohort (0.27 mg/kg). Single doses were administered intravenously and changes from baseline values of left ventricular EF were measured for each patient. Key findings include: Robust dose-dependent changes in a biomarker of target engagement Meaningful changes in LVEF observed across all dose groups in comparison with placebo: Placebo 0.03 mg/kg 0.09 mg/kg 0.27 mg/kg Mean Baseline LVEF (absolute) 31% 34% 28% 25% Relative mean change from baseline at Day 30 +4% +20% +19% +22% Relative mean change from baseline at Day 60 -6% +14% +28% +50% Relative mean change from baseline at Day 90 -19% +9% +27% +14% Relative mean change from baseline at Day 135 -33% +5% +23% +43% Relative mean change from baseline at Day 180 +10% +7% +49% +31% JK07 has been generally well-tolerated with most adverse events mild to moderate. Only one serious adverse event occurred (Grade 3), at the top dose level. A double-blind, randomized, multiple-dose Phase 2 trial of JK07 in patients with HFrEF and HFpEF is expected to begin in 1H 2024. About Heart Failure Heart failure affects an estimated 6.2 million Americans1 and more than 64 million people worldwide2. Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) each affect over 3 million patients in the US alone. Heart failure is a chronic condition in which patients experience progressively worsening symptoms and quality of life, hospitalizations and death. In HFrEF, the left ventricle loses its ability to contract normally, and the heart cannot pump with sufficient force to push enough blood into circulation. In HFpEF the heart becomes stiff and loses its ability to function properly. JK07 is in development for the treatment of both HFrEF and HFpEF. About JK07 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 heart failure, but also undesirable side effects. Research has shown that NRG-1 induces signaling through interaction with two different receptors – ErbB3 and ErbB4. The ErbB4 pathway appears to be responsible for the regenerative effects in the heart, while the ErbB3 pathway appears primarily responsible for safety and tolerability limitations of recombinant NRG-1. By blocking ErbB3 signaling with an antibody fusion design, JK07 selectively stimulates the 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. About SalubrisBio 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. 1 Centers for Disease Control and Prevention, Heart Failure, , (accessed May 8, 2023). 2 Groenewegen, A., Rutter, F., Mosterd, A., & Hoes, A. (2020). Epidemiology of heart failure. European Journal of Heart Failure, 22(8), 1342-1356.

GAITHERSBURG, Md.--( BUSINESS WIRE )--Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced positive updated results from the ongoing Phase 1b study of JK07 in heart failure with reduced ejection fraction (HFrEF). The data were presented in a late breaking oral session during the annual congress of the European Society of Cardiology’s Heart Failure Association. JK07 is the first investigational antibody fusion protein and first selective ErbB4 agonist to enter clinical development for heart failure. Heart failure is a serious health condition that contributes to one in eight deaths in the U.S. and impacts nearly 6.5 million Americans 1 . Fourteen patients were randomized 3 to 1 (11 JK07 : 3 placebo), with five patients in each of the first two cohorts (0.03mg/kg and 0.09 mg/kg, respectively), and four in the third cohort (0.27 mg/kg). Single doses were administered intravenously and changes from baseline values of left ventricular EF were measured for each patient. Results from the study were presented by principal investigator Dr. W. H. Wilson Tang, Research Director and staff cardiologist in the Section of Heart Failure and Cardiac Transplantation Medicine at the Cleveland Clinic. Key findings include: Robust dose-dependent biomarker changes demonstrated target engagement at all dose levels. Meaningful changes in LVEF were observed across all dose groups in comparison with placebo: Placebo 0.03 mg/kg 0.09 mg/kg 0.27 mg/kg Mean Baseline LVEF (absolute) 31% 34% 28% 25% Relative mean change from baseline at Day 30 +4% +20% +19% +22% Relative mean change from baseline at Day 60 -6% +14% +28% +50% Relative mean change from baseline at Day 90 -19% +9% +27% +14% JK07 has been generally well-tolerated with most adverse events mild to moderate. Only one serious adverse event occurred (Grade 3), at the top dose level. “Heart failure is a leading cause of morbidity and mortality in the US and globally. These new interim results demonstrate that JK07 achieved robust target engagement and encouraging signs of potential clinical benefit with a single administration,” said Sam Murphy, Chief Executive Officer of SalubrisBio. “The durable and sustained responses observed, coupled with a favorable safety profile, support further investigation of JK07 and we look forward to building upon these findings with the initiation of a Phase 2 trial later this year." A double-blind, randomized, repeat-dose Phase 2 trial of JK07 in patients with HF is expected to initiate in the second half of 2023. About Heart Failure Heart failure affects an estimated 6.2 million Americans 2 and more than 64 million people worldwide 3 . Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) each affect over 3 million patients in the US alone. Heart failure is a chronic condition in which patients experience progressively worsening symptoms and quality of life, hospitalizations and death. In HFrEF, the left ventricle loses its ability to contract normally, and the heart cannot pump with sufficient force to push enough blood into circulation. In HFpEF the heart becomes stiff and loses its ability to function properly. JK07 is in development for the treatment of both HFrEF and HFpEF. About JK07 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 heart failure, but also undesirable side effects. Research has shown that NRG-1 induces signaling through interaction with two different receptors – ErbB3 and ErbB4. The ErbB4 pathway appears to be responsible for the regenerative effects in the heart, while the ErbB3 pathway appears primarily responsible for safety and tolerability limitations of recombinant NRG-1. By blocking ErbB3 signaling with an antibody fusion design, JK07 selectively stimulates the 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. About SalubrisBio 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. ___________________________________ 1 https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-type-heart-failure . 2 Centers for Disease Control and Prevention, Heart Failure, https://www-cdc-gov.libproxy1.nus.edu.sg/heartdisease/heart_failure.htm , (accessed May 8, 2023). 3 Groenewegen, A., Rutter, F., Mosterd, A., & Hoes, A. (2020). Epidemiology of heart failure. European Journal of Heart Failure, 22(8), 1342-1356. https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/10.1002/ejhf.1858