SillaJen Submits CSR to the US FDA for REN026 Study in Patients with RCC

SEOUL, South Korea–(BUSINESS WIRE)–#BAL0891—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 profile and 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 profile and 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 www.sillajen.com.

Contacts

Investment Relations

Jeong Seok Lee

+82-2-368-2638

js1026@kr.sillajen.com

Public Relations

Jihwan Park

+82-2-368-2643

jayp@kr.sillajen.com