Salubris Biotherapeutics, Inc.

JK06 is the first clinical-stage biparatopic ADC targeting the cancer-associated oncofetal protein 5T4, for which no approved therapies currently exist GAITHERSBURG, MD, USA I August 05, 2024 I Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced it has received approval from the European Medicines Agency (EMA) to initiate a Phase 1 clinical trial of JK06 in a basket of solid tumors known to express 5T4. 5T4 is an oncofetal protein that is overexpressed in a wide range of tumor types, including lung, breast, renal and genitourinary cancers, and is associated with a poor prognosis and more aggressive tumor progression. JK06 is a first-in-class quadrivalent, biparatopic antibody drug conjugate (ADC) that selectively targets 5T4 with an MMAE payload. JK06 has demonstrated picomolar affinity for 5T4 and rapid internalization due to the biparatopic design. Together with stable, site-specific payload conjugation, JK06 has further demonstrated robust efficacy and a clean safety profile in non-clinical studies. “JK06 has shown an exceptional therapeutic window in non-clinical evaluation, and we believe it has the potential to be a first-in-class and differentiated therapy for patients with 5T4-associated cancers,” said Sam Murphy, Chief Executive Officer of SalubrisBio. “We are thrilled to be advancing into the clinic following the EMA’s decision and explore JK06’s ability to improve outcomes for patients.” JK06 will be evaluated in an open-label, dose-escalation and expansion study to assess the safety, pharmacokinetics, and preliminary efficacy of JK06. Phase 1 recruitment is expected to commence in Q3 2024, with up to 155 subjects planned for enrollment. “5T4 is a very promising tumor target, highly expressed on tumor cells from multiple cancer types as opposed to normal adult tissue and correlated with poor prognosis. 5T4 upregulation is playing a major role in the cancer heterogeneity, aggressiveness and metastatic potential, all of which are key factors that make these cancers harder to treat,” said Dr Nuria Kotecki, from Jules Bordet Institute in Brussels. “JK06 holds significant therapeutic potential by enhancing binding affinity and specificity, allowing for more effective delivery of cytotoxic agents directly to 5T4 cells, and we look forward to further evaluating it’s utility in the Phase 1 clinical trial.” About SalubrisBio SalubrisBio is a clinical-stage biotechnology company dedicated to discovering and developing complex biologics for cardiovascular, oncology, and neurodegenerative diseases. The Company is currently progressing multiple innovative and rationally designed first-in-class therapeutics through clinical development programs, including JK07, the potential first disease-modifying biologic for heart failure; JK08, an IL15-CTLA4 antibody fusion designed to expand the therapeutic window for these two potent immune-stimulating agents in cancer treatment; and JK06, a quadrivalent, biparatopic ADC targeting 5T4 for the treatment of cancer. SalubrisBio is headquartered in Gaithersburg, Maryland. For more information about SalubrisBio, visit us at www.salubrisbio.com and connect with us on LinkedIn . SOURCE: SalubrisBio

Shenzhen Salubris commits additional funding to continue research and development of novel, complex biologics First patient enrolled in RENEU-HF, the Phase 2 clinical trial of JK07 in heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) Clinical trial application filed for JK06, SalubrisBio’s first-in-class biparatopic ADC GAITHERSBURG, Md.--(BUSINESS WIRE)-- Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced a new capital infusion of $35 million to fund continued research and development of clinical and pre-clinical programs. SalubrisBio also provided progress updates for JK07, the first investigational antibody fusion protein for heart failure, JK08, the first investigational IL15-CTLA4 antibody fusion for solid tumors and JK06, a first-in-class biparatopic antibody-drug conjugate (ADC) targeting a known tumor antigen. “We are pleased with the clinical progress across our pipeline of novel, complex biologic therapeutics, positioning us for multiple inflection points over the coming year and into 2025,” said Sam Murphy, Chief Executive Officer of SalubrisBio. “Enrollment of the first patient in our Phase 2 clinical trial of JK07 is an important milestone in our heart failure program. Promising 6-month, Phase 1b data reported last year suggests that JK07 has the potential to improve heart function and long-term outcomes. We look forward to building on these promising findings and potentially delivering a new treatment option that can restore quality of life for heart failure patients.” JK07 Phase 2 Study Design RENEU-HF (NCT06369298) is a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose trial designed to evaluate the efficacy and safety of JK07 in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The study is expected to enroll 282 subjects who will be randomly assigned (1:1:1) to receive multiple doses of JK07 low dose, JK07 high dose, or placebo. The co-primary endpoints for HFrEF are improvement in ejection fraction, and safety and tolerability, and the primary endpoint for HFpEF is safety and tolerability. Together, HFrEF and HFpEF affect an estimated 6.2 million Americans1 and more than 64 million people worldwide2. Heart failure is a chronic condition in which patients experience progressively worsening symptoms and quality of life, hospitalizations and death. JK08 Phase 1b/2 Study Progress 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. More than fifty subjects have received JK08 monotherapy in the ongoing dose escalation cohorts, and the first patient has now been dosed in the cohort expansion phase, which will further define the safety and initial efficacy of JK08 in combination with targeted agents including pembrolizumab. SalubrisBio plans to report additional data from this study in the second half of 2024. “We are encouraged by the early data observed in the ongoing dose escalation portion of the JK08 Phase 1b/2 study and look forward to exploring the clinical benefit of combining JK08 with pembrolizumab in solid tumors,” added Murphy. JK06 CTA Filing JK06 is positioned to be the first biparatopic ADC targeting a known tumor antigen for which no approved therapies currently exist. Given limited expression and internalization, this antigen is ideally suited for the biparatopic design intended to overcome both limitations, and JK06 has demonstrated low picomolar affinity and robust internalization of the target. It has further demonstrated a highly favorable risk:benefit pro and will now be evaluated in a dose-escalation study, including a basket of solid tumors. 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 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. _________________________ 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.

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.