On March 1, 2023 INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported financial results for the quarter and year ended December 31, 2022, and provided a business update (Press release, Inovio, MAR 1, 2023, View Source [SID1234627980]). INOVIO’s management will host a live conference call and webcast with slides at 4:30 p.m. Eastern Time today to discuss financial results and provide a general business update for the fourth quarter. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

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INOVIO’s President and Chief Executive Officer, Dr. Jacqueline Shea, said, "The last year has been one of transition for INOVIO. We chose to make some difficult but essential decisions to best position our pipeline and organization for the future, and we are a stronger company because of it. We’ve honed our strategic vision, strengthened our financial position, and maintained our cash runway into first quarter 2025, enabling us to focus energy and resources on advancing candidates with scientific promise, achievable pathways to market, and strong commercial potential. Our continued commitment to financial discipline and operational excellence will guide us as we work to get those candidates across the finish line and ultimately deliver on the promise of DNA medicines for patients."

Dr. Shea continued, "Discussions are underway regarding next steps for our candidates with the greatest potential for impact, including INO-3107 as a potentially life-changing treatment for Recurrent Respiratory Papillomatosis (RRP) and INO-4201 as an Ebola vaccine booster. Today we also shared data from REVEAL2, the second trial in our program evaluating VGX-3100 as a treatment for cervical high-grade squamous intraepithelial lesions (HSIL). While the investigational biomarker-selected population did not achieve statistical significance, trial results did achieve statistical significance in the all-participants population. The overall evidence of viral clearance observed is encouraging as it builds upon the growing body of work pointing to the potential of our DNA Medicines platform in HPV diseases. We will certainly take that into consideration as we assess next steps for VGX-3100 and our broader portfolio. I believe that our increased experience with HPV therapeutics, coupled with our strengthened strategic focus over the past year, positions INOVIO to make meaningful advancements in our mission to bring innovative, life-saving DNA medicines to market."

Corporate Updates

REVEAL2 Data Results for VGX-3100 in Cervical HSIL

INOVIO reported results for REVEAL2. The company previously announced this trial was no longer pivotal and would not lead to a biologics license application (BLA) for a biomarker-selected population, as the U.S. Food and Drug Administration (FDA) had indicated that one or more additional trials would be required.

REVEAL2 was the second Phase 3 trial evaluating VGX-3100 for efficacy, safety, tolerability, and immunogenicity in treating HPV-16/18-related cervical HSIL. Trial participants included 203 women, 18 years of age or older, with histologically-confirmed cervical HSIL associated with HPV-16 and/or HPV-18, but who were otherwise healthy (NCT03185013). Participants received either VGX-3100 or placebo at weeks 0, 4 and 12 (randomized 2:1). In April 2022, the trial was amended to utilize a biomarker-selected population as the primary population, based on prior analysis that this investigational biomarker had the potential to identify women more likely to respond to treatment with VGX-3100.

In this trial, statistical significance was not achieved in the investigational biomarker-selected population for the endpoint of lesion regression and viral clearance. However, statistical significance was achieved in the all-participants population for the endpoint of lesion regression and viral clearance.

The percentage of participants in the investigational biomarker-selected population meeting the primary endpoint was 28.6% (6/21) in the treatment group, versus 0% (0/4) in the placebo group (p=0.115; difference in percentage 28.6, 95%CI: -24.6, 50.4), which was not statistically significant.

The result for the secondary endpoint of regression of HSIL and clearance of virus in the all-participants population of 203 participants (134 participants in the treatment group, 69 in the placebo group) was statistically significant, with 27.6% (37/134) of the participants meeting the endpoint in the treatment group, versus 8.7% (6/69) in the placebo group (p=0.001; difference in percentage 18.9, 95%CI: 7.8, 28.6).

In particular, in the all-participants population of REVEAL2, viral clearance was observed in 37.3% (50/134) in the 3-dose treatment group versus 8.7% (6/69) in the placebo group. Given the importance of viral clearance in removing the underlying cause of the HPV-related diseases, this data may have positive implications for our other HPV-related programs.

An ad-hoc integrated efficacy analysis of the results for both REVEAL1 and REVEAL2 shows statistical significance in both the biomarker-selected and all-participants populations. For the combined biomarker-selected population of 92 participants (68 participants in the treatment group, 24 in the placebo group), the percentage of participants meeting the endpoint was 54.4% (37/68 in the treatment group, versus 12.5% (3/24) in the placebo group (p<0.001; difference in percentage 41.9, 95%CI: 20.4, 57.0). For the combined all-participants population of 404 participants (272 participants in the treatment group, 132 in the placebo group), the percentage of participants meeting the endpoint was 25.0% (68/272 in the treatment group, versus 9.8% (13/132) in the placebo group (p<0.001; difference in percentage 15.2, 95%CI: 7.4, 22.1).

This combined data set will be used as supportive data in future regulatory interactions involving VGX-3100. As in REVEAL1, VGX-3100 was well-tolerated in REVEAL2. There were no treatment-related serious adverse events and most adverse events were considered to be mild to moderate.

INOVIO will continue to evaluate the results to determine the path forward for VGX-3100 in our HPV programs and plans to submit the data for publication in a peer-reviewed journal later this year. The Phase 3 trial of VGX-3100 in Greater China is currently ongoing, and INOVIO is working together with its development partner ApolloBio under our collaboration agreement, with the shared goal of advancing a treatment with the potential to improve the lives of patients in that market.

Clinical Highlights

Over the last year, positive data were announced for multiple programs in clinical development, including:

INO-3107 – RRP
INOVIO announced positive results from a Phase 1/2 clinical trial evaluating INO-3107 for the treatment of HPV 6 and HPV 11-related RRP in adults. Results from the first cohort of 21 participants showed a statistically significant improvement in the clinical endpoint of the number of surgical interventions needed to control papilloma growth, with a median decrease of three surgical interventions. In the second cohort of 11 patients, which delivered INO-3107 via exploratory side port needle, 10 of the 11 patients (91%) saw a reduction in number of surgeries in the year following initial treatment, with measurement beginning at Day 0, the start of trial therapy. Of these 10, four patients needed no surgery. There was a median decrease of three surgical interventions when comparing the year following treatment to the year prior, which was also statistically significant. In the year prior to treatment, the range of surgical interventions for these 11 patients was 2 to 8 and the median was 5. In both cohorts, INO-3107 was well-tolerated and immunogenic.

In both cohorts, patients received four doses of INO-3107: on Day 0, and Weeks 3, 6, and 9. Surgery was performed once in the two weeks prior to the first dose in order to establish a disease baseline, but any surgery performed following Day 0, including in the dosing window, was counted against the efficacy endpoint.

Conversations with regulators regarding development plans for INO-3107 are ongoing. INOVIO will present the Phase 1/2 trial results for INO-3107 at the 103rd Annual Meeting of the American Broncho-Esophageal Association at the 2023 Combined Otolaryngology Spring Meetings in May.

INO-4201 – Ebola Booster for rVSV-ZEBOV (Ervebo)
In a recently announced Phase 1b clinical trial in healthy adult participants who previously received a single injection of Ervebo, INO-4201 was found to be well-tolerated and boosted humoral responses in 100% (36 of 36) of treated participants. INOVIO believes these data indicate that DNA medicines could be an important part of global medical countermeasures against infectious diseases, either as primary vaccines or boosters to existing vaccines. INOVIO is currently in discussions with collaborators and potential partners regarding the next steps for the program.

INO-5401 – GBM
In 2022, INOVIO announced promising results from a Phase 1/2 trial of INO-5401 and INO-9012 in combination with PD-1 inhibitor Libtayo (cemiplimab) in newly diagnosed GBM patients. The data from this trial showed encouraging median overall survival data from 52 patients and evidence of antigen-specific T cells that may infiltrate GBM tumors.

INO-3112 – HPV-Related Cancers
In February 2022, updated results were published in Clinical Cancer Researchwhich included an improved Overall Response Rate (ORR) from a Phase 1b/2a trial in which the safety and tolerability, anti-tumor activity, and immunogenicity of INO-3112, when used in combination with durvalumab, a PD-L1 checkpoint inhibitor, was evaluated as a potential treatment for HPV-related head and neck cancer. The ORR was updated from 22.2% with three complete responses and three partial responses, to an ORR of 27.6% with four complete responses and four partial responses. As previously announced, the INO-3112 program was returned to INOVIO in 2021 from AstraZeneca.

Fourth Quarter 2022 Financial Results

As of December 31, 2022, cash and cash equivalents and short-term investments were $253.0 million compared to $401.3 million as of December 31, 2021. As of December 31, 2022, INOVIO had 253.1 million common shares outstanding and 271.0 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding options, restricted stock units, convertible preferred stock, and convertible debt.

Total revenue was $125,000 and $10.3 million for the quarter and year-ended December 31, 2022, respectively, compared to $839,000 and $1.8 million for the same period in 2021, respectively. The year-over-year increase in revenue resulted from the fulfillment of obligations under INOVIO’s contract with the U.S. Department of Defense.

Total operating expenses were $56.1 million and $277.8 million for the quarter and year-ended December 31, 2022, respectively, compared to $106.3 million and $303.0 million for the same period in 2021.

INOVIO’s net loss for the quarter and year-ended December 31, 2022 was $54.5 million, or $0.22 per basic and diluted share, and $279.8 million, or $1.17 per basic and diluted share, respectively, compared to net loss of $106.9 million, or $0.50 per basic and diluted share, and $303.7 million, or $1.45 per basic and diluted share, for the quarter and year-ended December 31, 2021, respectively.

Operating Expenses

Research and development (R&D) expenses for the quarter and year-ended December 31, 2022, were $42.1 million and $187.7 million, respectively, compared to $92.3 million and $249.2 million, respectively, for the same periods in 2021. The year-over-year decrease in R&D expenses was primarily related to lower drug manufacturing, outside services and clinical study expenses related to INO-4800 and VGX-3100, expenses related to the acquisition and installation of manufacturing equipment for INO-4800 during 2021 which were non-recurring, lower engineering services and expensed equipment related to our CELLECTRA 3PSP device array automation project, lower expensed inventory related to the CELLECTRA 2000 device and lower employee stock-based compensation. These decreases were offset by $29.2 million lower contra-research and development expenses recorded from grant agreements, $14.4 million of increased drug manufacturing costs related to our COVID-19 variant studies and DARPA COVID-19 dMAb grant and other variances.

General and administrative (G&A) expenses were $14.0 million and $90.2 million, respectively, for the quarter and year ended December 31, 2022, versus $14.0 million and $53.8 million, respectively, for the same periods in 2021. The year-over-year increase in G&A expenses was primarily due to a $14.0 million non-cash expense related to the settlement of INOVIO’s securities class action litigation, including the issuance of INOVIO common stock as part of the settlement, $14.3 million in higher legal expenses, primarily related to litigation matters, $6.9 million in one-time severance expenses and $1.6 million in higher employee compensation, among other variances.

INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s annual report on Form 10-K for the year ended December 31, 2022, which can be accessed at: View Source

Financial Guidance

INOVIO expects to maintain its cash runway into the first quarter of 2025. This projection includes its cash burn estimate of approximately $32 million for the first quarter 2023 and its ongoing expectation that cash burn will decrease incrementally from there into the first quarter of 2025. These projections do not include any funds that may be raised through the Company’s existing at-the-market program or other capital-raising activities.

Conference Call / Webcast Information

INOVIO’s management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO’s financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source