OncoSec Announces Clinical Data of the KEYNOTE-695 Trial Assessing TAVO™-EP in Combination with KEYTRUDA® (pembrolizumab) in Patients with Advanced Melanoma Refractory to anti-PD-1 Treatment

EWING, N.J. and SAN DIEGO, April 3, 2023

Among 98 efficacy evaluable patients with at least one post-baseline tumor assessment, the confirmed ORR per RECIST v1.1 by BICR assessment is 10.2% (95% confidence interval: 5.00, 17.97), which did not achieve the pre-specified clinically meaningful ORR of ≥17% (95% CI: 10.2, 25.8). The BICR results for 98 efficacy evaluable patients are lower than the ORR per RECIST v1.1 by investigator assessment of 18.8% for the 101 patients previously reported as the key secondary endpoint of the KEYNOTE–695 trial.

BICR assessment, i.e., review of the available images of treated and non-treated lesions by radiologists and oncologists, blinded to investigator assessments, showed that 4 patients had a complete response (CR), 6 patients had a partial response (PR), and 25 patients had stable disease (SD) as a best response, for a disease control rate (CR + PR + SD) of 35.7%. The durable response rate of ≥24 weeks is 8.2% and the median duration of response is 25.5 months (range: 6.83-not reached).

As previously reported, the median overall survival for all enrolled 105 patients was 22.7 months (95% CI: 14.4, 35.5), after a median follow-up period of 33.4 months. The combination therapy of TAVO™-EP and pembrolizumab was generally well tolerated with Grade 3 treatment-related adverse events (TRAEs) in 4.8% of all enrolled patients. No patients in the KEYNOTE-695 trial or any other clinical trials evaluating TAVO™-EP alone or in combination experienced Grade 4 or Grade 5 TRAEs.

The Company plans to pursue TAVO™-EP in combination with anti-PD-1 therapy in the neoadjuvant melanoma setting
Advancing TAVO™-EP in neoadjuvant melanoma is supported by data from an investigator-sponsored trial (IST) led by Dr. Ahmad Tarhini at H. Lee Moffit Cancer Center & Research Institute evaluating TAVO™  in combination with intravenous nivolumab (Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients - Full Text View - ClinicalTrials.gov). Interim data, presented in November 2022 as a poster (abstract #617) at the 37^th Annual Meeting of the Society of Immunotherapy of Cancer, showed high clinical (70% ORR by RECIST v1.1) and pathological response rates (88.9% major pathological response, including 66.7% complete pathological response). Of note, several patients predicted to be non-responders to immune checkpoint blockade by biomarker analysis prior to treatment appear to respond to TAVO™ in combination with nivolumab, supporting further the mechanism of action of IL-12. A meeting with the FDA to discuss a phase 2 randomized trial design and future development plans in the melanoma neoadjuvant setting is scheduled in May 2023.

"Treatment of patients with anti-PD-1 refractory melanoma remains difficult with limited success for immune checkpoint inhibitor combinations and exploratory therapeutic approaches. It is disappointing that review by blinded central readers did not confirm the previously reported results by investigator assessment of the KEYNOTE-695 Phase 2 clinical trial in this patient population. However, we remain optimistic that the observed long duration of response and overall survival of 22.7 months in this heavily pre-treated patient population, together with previously reported preliminary results from Dr. Tarhini's IST in the neoadjuvant melanoma setting, provide rationale for further development of TAVO™-EP in combination with anti-PD-1 therapy. We plan to discuss these data and a draft protocol for TAVO™-EP in combination with pembrolizumab for a randomized Phase 2 trial in the neoadjuvant setting at the upcoming meeting with the FDA to potentially initiate the trial in the second half of 2023," said Robert Arch, Ph.D., Chief Executive Officer of OncoSec. "I want to thank all patients who participated in the KEYNOTE-695 trial, the clinical teams who conducted this trial, and everybody at OncoSec who remain focused on developing TAVO™-EP as a novel intratumoral treatment approach for cancer patients with unmet medical needs."

About OncoSec Medical Incorporated
OncoSec Medical Incorporated (the "Company," "OncoSec," "we" or "our") is a biotechnology company focused on developing intratumoral immunotherapies to stimulate the patient's immune system to target cancer cells and eradicate disease. OncoSec's lead immunotherapy investigational product candidate – TAVO™ (tavokinogene telseplasmid) – enables the intratumoral delivery of DNA-based interleukin-12 (IL-12), a naturally occurring protein with immune-stimulating functions. The therapeutic approach TAVO™-EP, which employs electroporation, is designed to produce a localized expression of IL-12 in the tumor microenvironment and, thereby, stimulate the immune system to target and attack tumors. OncoSec's clinical pipeline is utilizing TAVO™ as a potential treatment for multiple cancer indications either as a monotherapy or in combination with checkpoint inhibitors; with the latter potentially enabling OncoSec to address a great unmet medical need in oncology: anti-PD-1 non-responders. Results from completed clinical trials of TAVO™ have demonstrated a local immune response, and subsequently, a systemic effect as either a monotherapy or combination treatment approach along with a well-tolerated safety profile, warranting further development of TAVO™-EP. For more information, please visit www.oncosec.com.