BAL0891

SEOUL, South Korea--(BUSINESS WIRE)-- SillaJen, Inc. (KOSDAQ: 215600) has submitted CSR to the US FDA on 06 Feb 2024 for REN026, a phase 1b/2a dose escalation and safety/efficacy evaluation study of Pexa-Vec in combination with cemiplimab in patients with metastatic or unresectable renal cell carcinoma (RCC). The study demonstrated an acceptable safety pro encouraging efficacy of the combination therapy of Pexa-Vec, an engineered oncolytic vaccinia virus, and Libtayo (cemiplimab), anti-PD-1 monoclonal antibody developed by Regeneron Pharmaceuticals Inc. (NASDAQ: REGN). In 2017, SillaJen began a collaboration agreement with Regeneron for the clinical study of Pexa-Vec in combination with cemiplimab in patients with RCC. Following the U.S. FDA IND approval in November 2017, SillaJen initiated the trial and 95 patients were enrolled from total of 21 clinical sites in the U.S., South Korea, and Australia. The study ended in February 2023. The study was conducted in four study arms (A to D) to assess the safety and efficacy of the Pexa-Vec in combination with cemiplimab. In Arm C, consisting of patients naïve to Immune checkpoint inhibitors (ICIs), Pexa-Vec in combination with cemiplimab showed the overall response rate (ORR) of 23.3% and the median overall survival (OS) of 25.13 months. Both ORR and OS were the highest compared to other study arms. In Arm D, patients with prior ICI treatment demonstrated ORR of 17.9 %, the second highest of the four arms. In particular, Arm D included 22 out of 28 patients (78.57%) with the three or more prior systemic regimens in metastatic setting and 5 patients (17.86%) with two prior treatments. Given the typically lower response rates in patients with more prior extensive treatments, the results are considered highly encouraging. About REN026 1) Background Pexa-vec (PV) is an oncolytic and immunotherapeutic vaccinia virus engineered to express GM-CSF. The REN026 study assessed the antitumor activity and safety of intravenous (IV) or intratumoral (IT) PV in combination with cemiplimab, anti-PD-1monoclonal antibody, in patients with metastatic or unresectable renal cell carcinoma (RCC). 2) Methods The study enrolled 95 patients in total, including 6 patients in dose-escalation phase and 89 patients with measurable histologically or cytologically confirmed metastatic or unresectable RCC were randomly assigned to one of four study arms. Patients naïve to immune checkpoint inhibitors (ICIs) with accessible tumors were randomized into Arm A (IT PV and cemiplimab) or Arm B (cemiplimab monotherapy, addition of IT PV upon disease progression). Patients naïve to ICIs with non-accessible tumors were placed in Arm C with IV PV and cemiplimab, and those with prior ICIs treatment were assigned to Arm D with IV PV and cemiplimab. PV was given IT (Arms A and B) administered every 2 weeks or IV (Arms C and D) weekly for 3 or 4 treatments as 1× 109 pfu. cemiplimab IV infusion (all study arms) was administered every 3 weeks, at a dose of 350 mg. 3) Results Between June 2018 and February 2023, 89 patients were assigned to the study arms as follows: 15 in Arm A, 16 in Arm B, 30 in Arm C, and 28 in Arm D. The overall response rate (by RECIST 1.1) across the arms were as follows: Arm A – 13.3% (2PR), Arm B – 12.5% (2 PR), Arm C – 23.3% (1 CR, 6 PR) and Arm D – 17.9% (5 PR). Median progression-free survival and overall survival for the arms were 4.27/22.0 months, 5.65/20.8 months, 4.57/25.1 months and 6.31/18.5 months, respectively. All patients experienced treatment-related AEs (any grade); 40 (45.5 %) experienced a grade 3 or 4 event. Pyrexia was the most common treatment-related AE. No Grade 5 events occurred in any of the study arms. 4) Summary of efficacy results A (n=15) B (n=16) C (n=30) D (n=28) ORR (95% CI)-% 13.3 (1.7-40.5) 12.5 (1.6-38.3) 23.3 (9.9-42.3) 17.9 (6.06-36.9) DCR (95% CI)-% 60.0 (32.3-83.7) 56.3 (29.9-80.2) 63.3 (43.9-80.1) 67.9 (47.6-84.1) PFS median (mo) (80% CI) 4.27 (2.37-NR) 5.65 (2.07-NR) 4.57 (4.34-15.44) 6.31 (3.29-NR) OS median (mo) (80% CI) 21.98 (21.98-NR) 20.83 (19.52-NR) 25.13 (22.01-NR) 18.53 (14.75-NR) 5) Conclusions The combination of IV Pexa-Vec and cemiplimab demonstrated an acceptable safety pro encouraging efficacy of ORR and survival with durable responses in patients with metastatic or unresectable RCC, regardless of previous ICI treatment. About Pexa-Vec and the SOLVE Platform Pexa-Vec is SillaJen’s representative investigational product from the company’s proprietary SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform. 595 cancer patients have been treated with Pexa-Vec as of 31 March, 2023, in multinational clinical trials. Pexa-Vec is engineered to target common genetic defects in cancer cells by deleting its thymidine kinase (TK) gene, thus making Pexa-Vec dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack. Pexa-Vec has been shown to be effective when delivered both intratumorally and systemically by intravenous administration. About SillaJen SillaJen, Inc. (KOSDAQ: 215600) is a publicly held biotech company developing anti-cancer therapies, with its clinical-stage products, Pexa-Vec, an oncolytic viral immunotherapy, and BAL0891, a mitotic checkpoint inhibitor. The company is also developing a unique CD-55 expressing vaccinia virus platform, GEEV®, which can be delivered to tumors via intravenous injection while evading the complement system and neutralizing antibodies against oncolytic viruses. Additional information about SillaJen is available at .

Continued commercial success of Cresemba and Zevtera in 2022 generated revenue contributions of approx. CHF 122 million, exceeding guidance by more than 17%Significant proceeds from oncology transactionsFollowing pre-NDA (New Drug Application) meeting held with FDA in Q4 2022 for ceftobiprole (Zevtera), NDA submission for three indications planned within two to three monthsBuilding a balanced R&D portfolio of antibacterial and antifungal drug candidates to support sustainable long-term growth in line with strategic refocus Ad hoc announcement pursuant to Art. 53 LR Basel/Allschwil, Switzerland, January 11, 2023 Basilea Pharmaceutica Ltd (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today the unaudited preliminary revenues for the financial year 2022 and provided an update on the progress made with its commercial brands Cresemba® (isavuconazole) and Zevtera® (ceftobiprole), as well as in advancing its R&D portfolio in 2022. Revenue contributions from the antifungal Cresemba and the antibiotic Zevtera are expected to amount to approximately CHF 122 million (full-year 2022 guidance: CHF 98 million – 104 million). Total revenue, which includes BARDA reimbursements1, proceeds from the oncology transactions and other revenue contributions in addition to the Cresemba and Zevtera contributions, is expected to amount to approximately CHF 148 million (full-year 2022 guidance: CHF 116 million – 122 million). David Veitch, Chief Executive Officer, commented: “We achieved significant milestones in 2022 and will continue to focus on delivering on our strategy to drive value creation going forwards. This is supported by the continued commercial success, especially of Cresemba and, subject to receiving a marketing approval in the U.S, the anticipated increasing revenue contributions from Zevtera. We are also planning to in-license further preclinical and clinical assets in 2023 and beyond. Our goal is to maintain a balanced portfolio of innovative drug candidates for the treatment of severe bacterial and fungal infections to support the long-term growth of Basilea, beyond Cresemba and Zevtera, and in so doing execute on our strategic goal of becoming a leading anti-infectives company.” The strong global commercial performance of Cresemba triggered a number of separate sales milestone payments to Basilea from its partners, related to Cresemba in-market sales; in the United States, Asia Pacific & China, Canada and the Nordics. By year-end 2022, Cresemba was approved in 73 countries and marketed in 63 countries, including the United States, most EU member states, China and additional countries inside and outside of Europe. According to the latest available market data, total global in-market sales of Cresemba in the twelve-month period between October 2021 and September 2022 amounted to USD 363 million, a 19 percent growth year-on-year.2 Anti-infectives key highlights 2022 Cresemba The intravenous and oral formulations of Cresemba were launched in China for the treatment of adult patients with invasive aspergillosis and invasive mucormycosis, marking the entry into one of the most important markets for novel antifungals.Patient recruitment was completed for the pediatric program. The completion of the pediatric program is a requirement for gaining an additional two years of marketing exclusivity in Europe and six months in the United States.In December, Basilea’s partner Asahi Kasei Pharma received the marketing approval for Cresemba in Japan for the treatment of adult patients with aspergillosis, mucormycosis, and cryptococcosis. Zevtera In June, Basilea announced positive topline results for the phase 3 ERADICATE study, evaluating ceftobiprole in the treatment of adult patients with bacterial bloodstream infections caused by Staphylococcus aureus (SAB).3 The ERADICATE study complements the TARGET phase 3 study in acute bacterial skin and skin structure infections (ABSSSI), which achieved positive results in 2019.4In July, Zevtera received the marketing authorization in Brazil. Dr. Marc Engelhardt, Chief Medical Officer, said: “In Q4 2022 we had a pre-NDA meeting with the U.S. Food and Drug Administration, which allowed us to finalize our regulatory strategy for ceftobiprole in the U.S. We will be seeking approval not only for Staphylococcus aureus bacteremia and acute bacterial skin and skin structure infections but also for community-acquired bacterial pneumonia. We aim to submit the corresponding New Drug Application within the next two to three months. While Staphylococcus aureus bacteremia is the indication of highest unmet medical need, we believe that a broader range of indications would further support the utility of ceftobiprole in a clinical practice setting.” Preclinical programs The work on an in-licensed DXR inhibitor program against multi drug-resistant Gram-negative bacteria progressed and Basilea expects to reach the next preclinical decision point in 2023.Progress on advancing earlier internal programs continues.Basilea has completed the profiling of a lead compound from a recently in-licensed preclinical program of broad-spectrum antifungals with a new mode of action. The candidate did not meet Basilea’s stringent criteria for progressing into the development stage and the company decided to return the program to the licensor. Dr. Laurenz Kellenberger, Chief Scientific Officer, commented: “We made good progress advancing our pipeline with promising programs, from both internal and external innovation. Our competencies and know-how in research and development of anti-infectives, combined with a data-driven approach and decision making process allows us to quickly identify and then focus on the most promising candidates for further development and for in-licensing.” Oncology transactions successfully completed in 2022 In February 2022, Basilea announced the strategic decision to focus exclusively on anti-infectives going forwards and to exit oncology by the end of 2022. By November 2022, Basilea had entered into three separate transactions with innovative oncology companies. These transactions related to novel preclinical stage inhibitors of PARG and CLK as well as BAL0891, a potential first-in-class mitotic checkpoint inhibitor. They were structured to provide upfront and near-term milestone payments, while also ensuring that Basilea maintains an ongoing participation in the long-term value creation potential of these promising programs. On the oncology assets which were not transacted, Basilea decided to transfer the rights for the FGFR inhibitor derazantinib back to Merck & Co. For the tumor checkpoint controller lisavanbulin, Basilea concluded the study program last year, following a decision not to expand glioblastoma patient cohorts, retaining the option to explore partnering opportunities in the future. Basilea will not incur material costs related to any oncology activities in 2023. About Basilea Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the needs of patients with severe bacterial and fungal infections. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of bacterial infections. In addition, we have several preclinical anti-infective assets in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com. Disclaimer This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning Basilea Pharmaceutica Ltd and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. For further information, please contact: Peer Nils Schröder, PhD Head of Corporate Communications & Investor RelationsBasilea Pharmaceutica International Ltd, Allschwil Hegenheimermattweg 167b4123 AllschwilSwitzerland Phone +41 61 606 1102 E-mail media_relations@basilea.cominvestor_relations@basilea.com This ad hoc announcement can be downloaded from www.basilea.com. References Basilea’s ceftobiprole phase 3 program is funded in part (up to USD 136.4 million, which is approximately 70% of the total potential program costs) with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number HHSO100201600002C.IQVIA Analytics Link, September 2022. In-market sales reported as moving annual total (MAT) in U.S. dollar.ERADICATE study: Clinicaltrials.gov identifier NCT03138733K. Hamed, M. Engelhardt, M. E. Jones et al. Ceftobiprole versus daptomycin in Staphylococcus aureus bacteremia: a novel protocol for a double-blind, Phase III trial. Future Microbiology. 2020 (1), 35-48TARGET study: ClinicalTrials.gov identifier NCT03137173J. S. Overcash, C. Kim, R. Keech R et al. Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET). Clinical Infectious Diseases 2021 (73), e1507-e1517 Attachment Press release (PDF)