Tavo (tavokinogene telsaplasmid) / OncoSec - LARVOL DELTA

Neoadjuvant Intratumoral Plasmid IL-12 Electro-Gene-Transfer and Nivolumab in Patients with Operable, Locoregionally Advanced Melanoma (Clin Cancer Res) - P2 | N=17 | NCT04526730 | "Sixteen patients were enrolled, and the preoperative radiological response rate was 63%. One patient declined surgery after experiencing a significant clinical response. Among the remaining 15 patients, the pCR rate was 60% and the MPR was 80%. No patient with MPR has had disease recurrence with a median follow-up from the date of surgery of 15.4 months. At baseline, most patients exhibited low CD8+ tumor-infiltrating lymphocytes, PD-L1, and IFN-γ gene expression signature."

P2 data • Melanoma

CORVax12: SARS-CoV-2 Spike (S) Protein Plasmid DNA Vaccine Trial for COVID-19 (SARS-CoV-2) (clinicaltrials.gov) - P1 | N=16 | Terminated | Sponsor: Providence Health & Services | Completed ➔ Terminated; Study was ended prematurely due to lack of efficacy. As per FDA guidance, our site continued to follow enrolled subjects through the 180 day safety visit.

Biomarker • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Neoadjuvant intratumoral plasmid interleukin-12 electro-gene-transfer and nivolumab in patients with operable locoregionally advanced melanoma. (PubMed, Clin Cancer Res) - "The clinical efficacy of neoadjuvant IT TAVO-EP + nivolumab is promising with 80% of patients achieving an MPR. Evidence of potent immune activation both systemically and within the TME along with a favorable safety profile supports the activity of local IL-12 and anti-PD1 based regimens."

IO biomarker • Journal • Metastases • Gene Therapies • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • IL12A • PD-L1

Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jul 2025 ➔ Jun 2028 | Trial primary completion date: Jul 2023 ➔ Jun 2028

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Feb 2025 ➔ Jul 2025 | Trial primary completion date: Feb 2025 ➔ Jul 2023

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Tumoral and systemic immune modulation with neoadjuvant (NeoAd) intratumoral (IT) TAVO-EP (plasmid IL-12 electro gene transfer) and nivolumab (NIVO) in patients (pts) with operable locoregionally advanced melanoma (AACR 2024) - P2 | "At baseline, most patients exhibited low CD8+ TIL, PD-L1 and TIS, with enhanced immune activation following treatment in the TME and blood including increased immune-related gene expression, CD8+ TIL, peritumoral CD8+ T cells and TIS. Four of 5 pts with negative predictive baseline biomarkers [CD8+TIL/PD-L1/TIS]low experienced pCRs supporting activity of IL12/anti-PD1 based regimens in this setting."

Clinical • IO biomarker • Metastases • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • IL12A • IL2 • JAK1 • PD-L1

Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Feb 2024 ➔ Feb 2025 | Trial primary completion date: Feb 2024 ➔ Feb 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2023 ➔ Feb 2024 | Trial primary completion date: Nov 2023 ➔ Feb 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Neoadjuvant (NeoAd) intratumoral (IT) TAVO-EP (plasmid IL-12 electro gene transfer) in combination with nivolumab (NIVO) for patients (pts) with operable locoregionally advanced melanoma (ESMO 2023) - P2 | "Conclusions NeoAd IT TAVO-EP and iv NIVO exhibited promising clinical activity and a favorable safety profile. Enhanced immune activation in responding patients supports the proposed immune mechanisms."

Clinical • Combination therapy • IO biomarker • Metastases • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • IL12A • PD-L1

Neoadjuvant Immunotherapy With Tavo + Electroporation in Combination With Nivo. in Melanoma Patients (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Recruiting ➔ Active, not recruiting | N=33 ➔ 17

Combination therapy • Enrollment change • Enrollment closed • Metastases • Melanoma • Oncology • Solid Tumor

KEYNOTE-890: Tavo and Pembrolizumab With or Without Chemotherapy in Patients With Inoperable Locally Advanced or Metastatic TNBC (clinicaltrials.gov) - P2 | N=65 | Active, not recruiting | Sponsor: OncoSec Medical Incorporated | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2023 ➔ Apr 2024

Combination therapy • Enrollment closed • Metastases • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PD-L1

OncoSec is encouraged after FDA meeting to discuss proposed neoadjuvant melanoma clinical program (PRNewswire) - "...The Company's discussion with the FDA follows the release of interim data from an ongoing investigator-sponsored trial (IST) led by Dr. Ahmad Tarhini...evaluating TAVO-EP in combination with intravenous nivolumab, which showed encouraging clinical and pathological response rates...The unmet clinical need in advanced melanoma together with previously reported interim results from Dr. Tarhini's IST in the neoadjuvant melanoma setting provide sound rationale for further development of TAVO-EP in combination with anti-PD-1 therapy prior to surgery."

OncoSec is encouraged after FDA meeting to discuss proposed neoadjuvant melanoma clinical program (PRNewswire) - "OncoSec Medical Incorporated...announced a Type C meeting held with the US Food and Drug Administration (FDA) on May 15, 2023. The purpose of the meeting was to discuss the trial design for a planned randomized, open-label Phase 2 clinical trial in patients with high-risk, resectable melanoma to evaluate the neoadjuvant treatment combination of the Company's tavokinogene telseplasmid, a plasmid encoding human interleukin 12 (IL-12), administered intratumorally by electroporation (TAVO™-EP) with intravenous KEYTRUDA^® (pembrolizumab), Merck's anti-PD-1 therapy. The meeting with the FDA represents an important next step on the Company's path to pursue clinical development of TAVO™-EP in combination with anti-PD-1 therapy in the neoadjuvant melanoma setting."

FDA event • Melanoma • Oncology • Skin Cancer • Solid Tumor

Neoadjuvant intratumoral TAVO-EP (plasmid IL-12 electro gene transfer) in combination with nivolumab; preliminary clinical and biomarker data in patients with operable locoregionally advanced melanoma (SITC 2022) - P2 | "There was evidence of significantly enhanced immune activation supporting the proposed immune mechanisms. Analyses of additional biomaterials are underway."

Biomarker • Clinical • Combination therapy • IO biomarker • Melanoma • Oncology • Solid Tumor • CD8 • IL12A • IL7R • KLRG1 • PD-1

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 (PRNewswire) - P2 | N=143 | Keynote-695 (NCT03132675) | Sponsor: OncoSec Medical Incorporated | "OncoSec Medical Incorporated...announced primary endpoint data from the Phase 2 KEYNOTE-695 clinical trial. This global, open-label single-arm trial is evaluating TAVO™-EP, OncoSec's proprietary interleukin 12 (IL–12) encoding plasmid delivered by intratumoral electroporation, in combination with KEYTRUDA^® (pembrolizumab), Merck's anti-PD-1 therapy, in patients with unresectable or metastatic (Stage III/IV) melanoma...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)."

P2 data • Melanoma • Oncology • Skin Cancer

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 (PRNewswire) - "The Company plans to pursue TAVO™-EP in combination with anti-PD-1 therapy in the neoadjuvant melanoma setting...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."

FDA event • Melanoma • Oncology • Skin Cancer

TAVO-EP Plus Pembrolizumab Fails to Meet ORR End Point in Anti–PD-1–Refractory Advanced Melanoma (Medscape) - "'However, we remain optimistic that the observed long duration of response and overall survival [OS] of 22.7 months in this heavily pretreated patient population, together with previously reported preliminary results from [an investigator-sponsored trial from Ahmad Tarhini, MD, PhD...] in the neoadjuvant melanoma setting, provide rationale for further development of TAVO-EP in combination with anti-PD-1 therapy.'"

Media quote

KEYNOTE 695: Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Either Pembrolizumab or Nivolumab Treatment (clinicaltrials.gov) - P2 | N=143 | Active, not recruiting | Sponsor: OncoSec Medical Incorporated | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Jul 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2023

Enrollment closed • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF

[VIRTUAL] Updated Clinical Data from KEYNOTE-695 (SITC 2021) - "Sponsored by OncoSec TAVO (IL-12) Intralesional Therapy Durable Responses in PD-1 Progressing Advanced Melanoma: Clinical Significance and Practicality of the Data"

Clinical data • Melanoma • Oncology • Solid Tumor • IL12A • PD-1

CORVax12: SARS-CoV-2 Spike (S) Protein Plasmid DNA Vaccine Trial for COVID-19 (SARS-CoV-2) (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Providence Health & Services | Active, not recruiting ➔ Completed | N=36 ➔ 16

Biomarker • Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

KEYNOTE 695: Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Either Pembrolizumab or Nivolumab Treatment (clinicaltrials.gov) - P2 | N=143 | Recruiting | Sponsor: OncoSec Medical Incorporated | Trial completion date: Jul 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF

OncoSec presents encouraging early data with TAVO-EP combined with nivolumab (Opdivo) in neoadjuvant melanoma (BioSpace) - "Ahmad Tarhini, MD PhD...'patients with locoregionally advanced operable melanoma carry a high risk of morbidities with the upfront surgical approach and continue to have a high risk of disease relapse and death....Patients are actively enrolling into this trial, and I am looking forward to presenting clinical data updates on more patients at a future medical conference.'"

Media quote

OncoSec presents encouraging early data with TAVO-EP combined with nivolumab (Opdivo) in neoadjuvant melanoma (PRNewswire) - P2 | N=33 | NCT04526730 | "OncoSec Medical Incorporated...announced early clinical data from an investigator-sponsored trial (IST) conducted by Dr. Ahmad Tarhini at the H. Lee Moffit Cancer Center & Research Institute. This IST is evaluating TAVO™, OncoSec's proprietary interleukin 12 (IL-12) encoding plasmid delivered by intratumoral electroporation (TAVO™-EP), in combination with intravenous nivolumab. Interim data were presented as a poster (abstract #617) at the 37th Annual Meeting of the Society of Immunotherapy of Cancer (SITC) in Boston, Massachusetts on November 10th....A preoperative overall response rate (ORR) by RECIST v1.1 was observed in 7 of 10 patients (70%) consisting of 4 patients with complete response (CR) and 3 patients with partial response (PR). Two patients had stable disease (SD) and 1 patient showed progressive disease (PD)."

P2 data • Melanoma • Oncology • Solid Tumor

OncoSec Announces Positive Clinical Data of the KEYNOTE-695 Trial Assessing TAVO-EP in Combination with Pembrolizumab (Keytruda) in Patients with Advanced Melanoma Refractory to anti-PD-1 Treatment (PRNewswire) - P2 | N=152 | KEYNOTE-695 (NCT03132675) | Sponsor: OncoSec Medical Incorporated | "OncoSec Medical Incorporated...announced data from the Phase 2 KEYNOTE-695 clinical trial. This global, open-label single-arm trial is evaluating TAVO™...in combination with pembrolizumab in patients with unresectable or metastatic (Stage III/IV) melanoma who had progressed on immediate prior anti-PD-1 antibody therapy....The key secondary endpoint of KEYNOTE-695 was met. Investigator assessment of overall response rate (ORR) per RECIST v1.1, from 101 efficacy evaluable patients, with at least one post-baseline tumor assessment, showed a confirmed ORR of 18.8% (95% confidence interval: 11.7, 22.8), which exceeds the pre-specified clinically meaningful ORR of ≥17% (95% CI: 10.2, 25.8)....Top-line results of the primary endpoint of the KEYNOTE-695 trial, ORR by blinded, independent central review (BICR) based on RECIST v1.1, are expected to be announced in the first quarter of 2023."

P2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

Trial in progress: Phase 2 study of intratumoral plasmid interleukin-12 (tavokinogene telseplasmid; TAVO™) plus electroporation in combination with pembrolizumab with or without chemotherapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (KEYNOTE-890/OMS-I141) (SABCS 2021) - P2 | "Patients will receive pembrolizumab (200 mg IV) every 3 weeks, TAVO-EP (0.5 mg/mL at dose volume of ~1/4 lesion volume) on Days 1, 5, and 8 every 6 weeks, and nab‑paclitaxel (100 mg/m 2 IV) on Days 1, 8, and 15 every 4 weeks. Based on positive efficacy data in Cohort 1, additional cohorts are being planned and will be presented. ClinicalTrials.gov: NCT03567720"

Clinical • Combination therapy • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • IL12A • PD-L1