Pexastimogene devacirepvec

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 .

Bota-vec has already been tested in a phase 1/2 study in adult and pediatric populations with the genetic disease X-linked retinitis pigmentosa, which causes blindness. MeiraGTx has handed off the remaining interests for a rare disease gene therapy to Johnson & Johnson in a deal that could reach $415 million. The agreement involves botaretigene sparoparvovec, or bota-vec, formerly AAV-RPGR, which is in development for X-linked retinitis pigmentosa. The therapy was developed through a partnership with J&J’s Janssen unit, but now the healthcare giant wants the whole program. Bota-vec has already been tested in a phase 1/2 study in adult and pediatric populations with the genetic disease that causes blindness, while a late-stage study completed enrollment this year. J&J’s Janssen pharmaceuticals unit will hand over $130 million upfront plus near-term milestones, with an additional $285 million possible upon first commercial sales in the U.S. and EU, according to the Thursday release. An initial milestone payment of $50 million is expected in the first quarter of 2024, MeiraGTx said. The companies have also reached to a commercial supply and technology transfer agreement for bota-vec. The J&J deal will help MeiraGTx shore up its resources heading into 2024. The upfront payment and near-term milestones, combined with an additional $30 million investment from French Big Pharma Sanofi in another deal received recently, will extend the biotech’s cash runway into mid-2026. MeiraGTx announced the Sanofi investment in October and told Fierce Biotech at the time that the company was seeking monetization of some pipeline assets as well. The J&J deal fits right into those efforts. Sanofi nabbed the right to access a first look at data from programs in immunology and inflammation, central nervous disorders and GLP-1 and other gut peptides for metabolic diseases. This could someday drum up deals between the two companies. Speaking of Sanofi, the French pharma did a little dealmaking of its own on Thursday when AI drug discovery-focused Exscientia announced that the two companies have expanded on a previous deal. The boosted pact now includes a new discovery stage program that the biotech had previously discovered and advanced. Details were slim, but the partners have an outstanding deal for up to 15 small molecules across oncology and immunology. Sanofi will now hand over $45 million extra upfront, plus milestones and other payments that could reach $300 million and royalties.