On March 22, 2023 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported a new study published in Cancer showing the prognostic and predictive utility of Natera’s personalized and tumor-informed molecular residual disease (MRD) test, Signatera, to inform adjuvant treatment decisions and monitor for recurrence and therapy response in patients with stages III-IV melanoma (Press release, Natera, MAR 22, 2023, View Source [SID1234629196]). The full study can be found here.

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This study analyzed 555 prospectively collected plasma samples from 69 patients with stages III-IV melanoma, analyzed in three cohorts. Key takeaways include:

Cohort A: Resectable stage III patients receiving immunotherapy or observation in the adjuvant setting:
MRD positivity post-resection was associated with significantly shorter distant metastasis-free survival (HR=10.77; p=0.01), and identified patients most likely to benefit from adjuvant therapy. Signatera detected recurrence with an average lead time of 3 months over standard imaging.
Cohort B: Unresectable stage III/IV patients receiving immunotherapy:
An increase in ctDNA levels 3-11 weeks after starting immune checkpoint inhibitor therapy was associated with significantly shorter progression-free survival (HR=22; p=0.006). All patients with increasing ctDNA experienced disease progression (4/4), while all patients with decreasing ctDNA achieved complete or partial response (15/15). In two patients, Signatera also correctly differentiated between true progression vs. pseudo-progression.
Cohort C: Stage III/IV patients in surveillance after completion of immunotherapy:
100% (7/7) of patients who were ctDNA-negative during surveillance remained progression-free until the last follow up (median 14.67 months), while all ctDNA-positive patients (3/3) experienced disease progression.
"ctDNA is emerging as a potential biomarker for informing adjuvant treatment decisions and assessing treatment response in metastatic disease in real-time," said Zeynep Eroglu, M.D., medical oncologist in the department of cutaneous oncology at Moffitt Cancer Center and lead author of the study. "Our study shows the potential for a personalized, tumor-informed ctDNA assay to help with making informed and timely treatment decisions for patients with advanced melanoma across treatment settings. We hope that this will be explored further in prospective clinical trials."

This new study builds upon prior literature supporting the validity and utility of Signatera for pan-cancer immunotherapy monitoring,1 which was the basis for Medicare’s local coverage determination issued in 2021. Although the use of immune checkpoint inhibitors has led to significant improvements in overall survival rates for patients with advanced melanoma,2-6 response can be difficult to assess and treatment related toxicity remains a problem. Current guidelines recommend periodic imaging and clinical assessment to determine therapeutic efficacy;7 however, imaging-based surveillance has limitations. This illustrates the unmet need for diagnostic tools, like Signatera, to help predict immunotherapy benefit in the adjuvant and metastatic settings and to identify patients early who have resistance to therapy.

"This collaborative analysis of real-world data supports the prognostic and predictive value of Signatera in the clinical management of melanoma patients after surgery, and those receiving an immune checkpoint inhibitor," said Minetta Liu, M.D., chief medical officer of oncology at Natera. "It is critical to balance treatment-related benefit with toxicity, and ctDNA assessment by Signatera provides a means by which to predict and evaluate benefit from immunotherapy in melanoma, the deadliest of all skin cancers."

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood, to identify recurrence earlier and to help optimize treatment decisions.

On March 22, 2023 BostonGene reported a collaboration with Little Warrior Foundation to drive the discovery, validation, and implementation of novel liquid biopsy solutions into sarcoma clinical practice (Press release, , MAR 22, 2023, View Source [SID1234629195]).

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Little Warrior Foundation was founded in 2020 with a simple mission to fund and find a lasting cure for childhood cancer, specifically focusing on Ewing Sarcoma. Funds the foundation raises are granted to researchers and institutions developing high-potential therapies and novel solutions for pediatric applications.

Sarcomas are malignant tumors originating in connective and supportive tissue and are incredibly diverse at the histological and molecular levels. Thus, in sarcomas, clinical decision-making often relies on the molecular features of each unique tumor. Further, sarcomas are fusion-rich, with various fusions as known drivers of myriad sarcomas, highlighting the importance of RNA-based analysis in sarcomas. Broad liquid biopsy panels have limited applicability for individual cancer types due to the unique molecular landscape of each cancer type; therefore, Little Warrior Foundation has partnered with BostonGene to develop sarcoma-specific cfDNA and cfRNA liquid biopsy assays to increase the sensitivity and accuracy of detecting sarcoma-related molecular alterations and fusions. In this collaboration, BostonGene will develop sarcoma-specific cfDNA and cfRNA liquid biopsy assays, aiming at implementing them into clinical practice for both pediatric and adult sarcomas.

"Our partnership with BostonGene enables us to accelerate research and development efforts by identifying novel solutions for patients with Ewing Sarcoma and related sarcomas," said Piero Spada, President and Co-Founder, Little Warrior Foundation. "We expect this collaboration to provide physicians with the necessary tools to monitor for relapse and reoccurrence in a more efficient manner, ultimately impacting integral clinical decisions for patients."

"We share a commitment with Little Warrior Foundation to develop and implement breakthrough solutions for patients with myriad sarcomas," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "BostonGene’s advanced sequencing and analytics will propel the development of more effective treatment strategies, ultimately positively impacting pediatric and adult patients."

On March 22, 2023 PeptiDream Inc., a public Kanagawa, Japan-based biopharmaceutical company (President and CEO: Patrick C. Reid, hereinafter "PeptiDream") (Tokyo: 4587) reported the nomination of the second targeted peptide radiopharmaceutical clinical development candidate arising from their strategic partnership with RayzeBio, Inc., ("RayzeBio"), a privately held California-based targeted radiopharmaceutical company developing innovative cancer drugs (Press release, PeptiDream, MAR 22, 2023, View Source [SID1234629194]). The development candidate is a novel first-in-class macrocyclic peptide-radioisotope (RI) conjugate against Glypican-3 ("GPC3") expressed in liver cancers. Liver cancer is a leading cause of death global, according for over 800,000 deaths annually.

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"We are delighted to announce the nomination of a second peptide-RI clinical development candidate arising from our partnership with RayzeBio, highlighting the strong collaborative relationship and the power of our PDPS platform to discover novel macrocyclic peptides for use as peptide-RI conjugates."

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The peptide-RI development candidate was discovered using PeptiDream’s proprietary Peptide Discovery Platform System (PDPS) and demonstrated potent and selective GPC3 binding, rapid cellular internalization, and sustained tumor specific uptake and anti-tumor efficacy in pre-clinical models at RayzeBio. RayzeBio intends to present initial preclinical data at the EASL Liver Cancer Summit in Estoril, Portugal on April 20. 2023. PeptiDream and RayzeBio have an ongoing multi-program collaboration, initiated in August 2020, to screen and identify novel peptide binders against tumor antigens for the targeted delivery of radioisotopes.

"We are delighted to announce the nomination of a second peptide-RI clinical development candidate arising from our partnership with RayzeBio, highlighting the strong collaborative relationship and the power of our PDPS platform to discover novel macrocyclic peptides for use as peptide-RI conjugates." said Patrick C. Reid PhD, President & CEO of PeptiDream.

About PeptiDream Inc.

PeptiDream Inc. (Tokyo Stock Exchange Prime Section 4587) is leading the translation of macrocyclic peptides into a whole new class of innovative medicines to address unmet medical needs and improve the quality of life of patients worldwide. Founded in 2006, PeptiDream employs its proprietary Peptide Discovery Platform System (PDPS) technology, a state-of-the-art highly versatile discovery platform which enables the production of highly diverse (trillions) non-standard peptide libraries with high efficiency, for the identification of highly potent and selective macrocyclic peptide candidates, which then can be developed into peptide-based, small molecule-based, peptide-drug conjugate (PDC) and multi-functional peptide conjugates (MPC)-based therapeutics and diagnostics. PeptiDream has an extensive global network of discovery and development partners driving the development and commercialization of a broad and diversified pipeline of investigational therapeutics. PeptiDream also markets and sells a number of radiopharmaceutical and radiodiagnostic products in Japan, through its wholly owned subsidiary, PDRadiopharma. PeptiDream is headquartered in Kawasaki, Japan. For more information about our company, science and pipeline, please visit www.peptidream.com

On March 22, 2023 Personalis, Inc. (Nasdaq: PSNL) reported it is presenting new research data as scientific posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, which convenes from April 14-19, 2023 in Orlando, Florida (Press release, Personalis, MAR 22, 2023, View Source [SID1234629193]).

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The data highlights the power of the company’s highly-discerning technologies that both characterize and monitor cancer, including initial research findings from a collaboration with University Medical Center Hamburg-Eppendorf (UKE) and its new Fleur-Hiege Center for Skin Cancer Research, where Dr. Klaus Pantel, Dr. Christoffer Gebhardt, and team are using NeXT Personal to track tumor response to immunotherapy (IO) in patients with melanoma, with the aim of gathering evidence to advance the use of ultra-sensitive minimal residual disease (MRD) detection in routine clinical practice for IO therapy monitoring.

"We are encouraged by initial findings from our research with Dr. Pantel and his team at UKE, which show that highly sensitive detection of circulating tumor DNA (ctDNA) may improve our ability to predict responses or resistance to therapy earlier than imaging," said Sean Boyle, Executive Director of Scientific Applications at Personalis. "Our deep expertise in genomic sequencing and commitment to scientific excellence have laid the foundation not only for our own MRD advancements, but also for exceptional partnerships with leaders in the field of oncology."

Boyle added, "We are also excited to share updates on NeXT Personal performance, with research data that shows the highly sensitive assay can detect MRD even in challenging samples, at earlier time points. The addition of clinically relevant tumor-agnostic actionable content makes NeXT Personal unique in its ability to both detect MRD and identify clinically relevant mutations that may be missed with other assays."

Details of the Personalis abstracts are outlined below, and further details about the poster presentations can be found at this link.

Title: Ultra-sensitive tumor-informed ctDNA assay predicts survival in advanced melanoma patients treated with immune checkpoint inhibition
Overview: Immune checkpoint inhibition (ICI) elicits clinical benefit in a subset of cancer patients, and monitoring of ctDNA in peripheral blood might improve our ability to predict responses or resistance earlier than imaging. In this study, we analyzed melanoma patients receiving ICI over several years using NeXT Personal, a novel tumor-informed ctDNA platform, and correlated the findings to clinical outcome. Patients that attained ctDNA clearance at one or more plasma timepoints had significantly longer overall survival (OS) and patients with increasing ctDNA levels over the first 25 (or 50) days compared to baseline had significantly reduced OS (p < 0.05). Results demonstrate the ultra-high sensitivity for ctDNA with a wide dynamic range of detections, and include de novo detection of emerging clinically actionable and resistance variants.

Title: Analytical performance of an ultra-sensitive, tumor-informed liquid biopsy platform for molecular residual disease detection and clinical guidance
Overview: Here we report a performance update of the NeXT Personal platform. Most ctDNA-based MRD detection methods leverage a limited genomic footprint, restricting detection sensitivity and thus their utility in many clinical settings. For example, early-stage, low tumor mutational burden (TMB) cancers may lack sufficient variants in these limited footprints to produce detectable signals. Further, insights into tumor evolution, including actionable mutations may be missed. Utilizing whole genome sequencing of tumor and normal DNA to guide design of bespoke MRD assays, we select up to 1800 high signal, low noise MRD targets and up to 400 exonic variants. Along with proprietary algorithms, this achieves high MRD sensitivity with a limit of detection of 1 ~ 3 parts per million. Additionally, specificity was demonstrated, showing variant detection is > 99.99% with 100% PPV, while individual variant content demonstrates high sensitivity at allele fractions of 0.1% and above, with high accuracy and signal linearity as confirmed by ddPCR (R2 = 0.998). Finally, to explore the utility of NeXT Personal in a clinical setting, a retrospective analysis was undertaken in an advanced liver cancer (low TMB). Our data demonstrate high analytical performance of the NeXT Personal platform in both MRD and individual variant detection.

Title: Utilizing response in immune checkpoint inhibitor treated cohorts improves clinical applicability of neoantigen immunogenicity predictions
Overview: Neoantigen-based biomarkers have improved predictions of response to immune checkpoint blockade (ICB) therapy, highlighting the importance of accurate prediction of immunogenic neoantigen candidates. In this study, we deployed a novel approach to optimize prediction models of immunogenic neoantigens using a meta-analysis framework based on multiple ICB cohorts, totaling over 500 patients. Through iterations of SHERPA-Immunogenicity (SI) models, we aggregated pMHC predictions into patient-specific scores based on the most immunogenic peptide present (SHERPA-Immunogenicity Maximum – SIM) or the quantity of immunogenic peptides identified (SHERPA-Immunogenicity Burden – SIB). We observed that responders had higher SIM and SIB scores compared to non-responders across the melanoma training cohorts, and that SIM scores outperformed SIB scores, suggesting the degree of epitope immunogenicity may be a critical factor in predicting response.

Title: Immune infiltrate co-occurrence and neoantigen similarity are prognostic factors in early stage NSCLC
Overview: By leveraging a comprehensive individual portrait of each patient’s immune system, potential novel mechanisms associated with tumor relapse in early-stage NSCLC may be identified. We profiled 11 non-relapsed lung adenocarcinoma (LUAD) patients and 11 covariate-matched (gender, age, stage) relapsed patients, who underwent curative treatment in stage IA-IIIB disease. In this pilot cohort, we used ImmunoID NeXT to broadly characterize both the tumor and immune system, enabling identification of relapse-associated neoantigens that may share universal features which enhance HLA binding. Relapses in early-stage LUAD patients were associated with neoantigens with lower immunogenicity and an immunosuppressive tumor microenvironment (TME). These findings demonstrate that deeper profiling of shared neoantigen features has the potential to become an early biomarker of relapse, informing patient therapy selection and surveillance.

On March 22, 2023 Virpax Pharmaceuticals, Inc. ("Virpax" or the "Company") (NASDAQ: VRPX), a company specializing in developing non-addictive products for pain management, post-traumatic stress disorder, central nervous system (CNS) disorders and viral barrier indications, reported its financial results for the twelve months ended December 31, 2022, and other recent developments (Press release, Virpax Pharmaceuticals, MAR 22, 2023, View Source [SID1234629192]).

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"We continue to make progress in our drug candidate programs as well as in our efforts to secure non-dilutive funding. Additionally, we have attracted leading physicians to advise on trial design, regulatory pathway and patient recruitment, as well as world-class partners to support our global sub-licensing plans for selected pipeline assets," commented Anthony P. Mack, Chairman and Chief Executive Officer of Virpax.

"The work on developing an improved formulation for Probudur, our leading drug product for postoperative pain management, has been completed. With this new formulation, we expect to demonstrate longer duration, manufacturing efficiencies and extended patent protection. We are working with Lipocure to scale up production of Probudur in anticipation of initiating Investigational New Drug Application (IND) enabling toxicity studies. It is currently expected that we will engage one of our CROs to initiate our pre-clinical animal studies towards the end of 2023.

"We recently announced that Dr. Neil Singla, a leading pain expert, will be working with Virpax to assist in the design and support of the clinical development strategy for Probudur. In addition, Dr. Singla will work with us on patient recruitment and establishing relationships with patient advocacy groups as well as submissions for potential grants and additional cooperative research and development agreements (CRADAs)," continued Mr. Mack.

"The Molecular Envelope Technology (MET) that we have in-licensed from Nanomerics Ltd. is serving as the foundation for our other two Rx programs, Envelta and NobrXiol. As stated previously, we expect to be able to reference the same MET preclinical data for both submissions, potentially saving us valuable time and money. With Envelta, the Company is working under our grant program with the National Center for Advancing Translational Sciences (NCATS) to scale up manufacturing in anticipation of an IND filing in 2024.

"With NobrXiol, we recently received our pre-IND guidance from the Food and Drug Administration ( FDA) to help guide us as we advance this drug candidate. To support our overall development plan, we have engaged two leading physicians experienced in pediatric epilepsy, Dr. Kenneth Sommerville and Dr. Lawrence Fried. Additionally, we have identified grant opportunities for NobrXiol and anticipate that Dr. Sommerville and Dr. Fried will assist our team in our grant and CRADA submissions," added Mr. Mack.

"We are moving forward with our non-dilutive financing strategy with both grants and licensing opportunities. Our grant team, in conjunction with outside experts, identifies and evaluates grant opportunities and CRADAs where we believe we have a strong chance of success. We have applications in process, as well as pending applications and will continue to pursue this strategic approach.

"Finally, we have engaged exclusive advisors for our partnering and licensing efforts in key global markets. New England Investors is leading our effort for Envelta in the People’s Republic of China. Before they could begin their work, we were required to obtain a patent in China, which we obtained this past November. To date, we are encouraged by the initial interest and responses they have received.

"Destum Partners, whom we have engaged to lead our global strategic partnering and licensing efforts for our two potential OTC products (EpoladermTM, indicated for osteoarthritis pain, and AnQlar, an intranasal mucosal viral barrier) and Probudur for the animal health market, have begun their outreach efforts. They are starting with Probudur and have identified several animal health care companies that have expressed initial interest. While these types of licensing deals take time to complete, we are optimistic based upon the level of interest to date.

"I believe we have a highly experienced and motivated team working to help us enter first-in-human trials. We have a solid strategy in place and expect that we will achieve some significant drug development milestones in 2023 as well as important regulatory milestones in 2024," concluded Mr. Mack.

RECENT DEVELOPMENTS

On December 8, 2022, Virpax received Pre-Investigational New Drug (PIND) application guidance from the FDA for NobrXiol. The main purpose of a PIND submission is to obtain FDA guidance on the overall development plan for a new drug and to identify any need for further data prior to submitting an IND.

NobrXiol is the Company’s product candidate for the delivery of cannabidiol in the management of epilepsy in children and adults that utilizes Nanomerics’ Molecular Envelope Technology (MET) as its delivery system to cross the blood brain barrier, propelling the cannabidiol nanoparticles through the nose to the brain via the olfactory nerve.
On January 4, 2023, Virpax announced that it has engaged two leading physicians experienced in childhood epilepsy, Dr. Kenneth W. Sommerville and Dr. Lawrence Fried, to support the overall development plan for NobrXiol. Their involvement with this program is expected to include advising on trial design, regulatory pathway development and patient recruitment. Additionally, it is anticipated that they will support Virpax with patient advocacy groups and grant applications.
On January 10, 2023, Virpax announced that that the Company has engaged Destum Partners, Inc. to serve as the exclusive advisor for the Company’s partnering and licensing efforts in strategic global markets. This initial engagement will encompass the Company’s OTC product candidates, Epoladerm, indicated for osteoarthritis pain, and AnQlar, an intranasal mucosal viral barrier. Additionally, Destum Partners will work with Virpax on identifying a partner in the animal health market for its Rx product candidate, Probudur, a long-acting local anesthetic indicated for postoperative pain management.
On January 18, 2023, Virpax announced that it will utilize leading pain expert, Dr. Neil K. Singla, to assist in the design and support of the clinical development strategy for Probudur. Probudur is Virpax’s post-operative, long-acting anesthetic injection product candidate that is being developed to significantly reduce or eliminate the need for opioids after surgery in approved indications.
On January 31, 2023, Virpax announced the Company has engaged New England Investors, LLC to serve as the out-licensing advisor for Envelta in the People’s Republic of China. Envelta is Virpax’s non-opioid pain product candidate for acute and chronic pain including non-cancer pain that is being funded under an in-kind grant from NCATS, part of the National Institutes of Health (NIH).
On February 13, 2023, Virpax announced that the Company has completed FDA required preclinical toxicology studies for its licensed Molecular Envelope Technology. The Company believes MET may enhance the delivery of Virpax’s Envelta and NobrXiol product candidates. MET is also utilized in the Company’s AnQlar product candidate. These preclinical toxicology studies were performed to evaluate the safety of the MET platform and support the IND submission of each product candidate.
FINANCIAL RESULTS FOR THE YEARS ENDED DECEMBER 31, 2022 AND 2021

Twelve Months Ended December 31, 2022

Operating Expenses

General and administrative expenses increased by $3,896,078, or 54%, to $11,082,463 for the year ended December 31, 2022, from $7,186,385 for the year ended December 31, 2021. The primary reasons for the increase in general and administrative costs were (i) an increase in legal costs associated with litigation defense efforts of $3,417,321, including a $2,000,000 estimated litigation liability, (ii) an increase in salaries and wages and employee benefits of $257,438, (iii) an increase in insurance costs related to directors’ and officers’ insurance of $216,134, (iv) an increase in non-executive board compensation of $181,667, and (v) an increase in grant writing and grant consulting fees of $114,973. This was offset by a decrease in stock-based compensation of $316,768.

Research and development expenses increased by $5,923,555, or 122%, to $10,762,670 for the year ended December 31, 2022, from $4,839,115 for the year ended December 31, 2021. The increase was primarily attributable to (i) an increase in preclinical activity of $3,826,920 related to AnQlar’s ongoing IND enabling studies and regulatory consulting, in addition to an increase in milestone payments of $500,000 made to Nanomerics related to AnQlar, (ii) an increase in NobrXiol of $599,800 mainly due to a milestone payment of $500,000 paid to Nanomerics upon achieving the study aim contained within a pre-clinical animal study,(iii) increases in preclinical and regulatory activity related to Epoladerm of $513,517, and (iv) an increase in preclinical work related to Probudur of $487,573 related to ongoing formula optimization.

Cash Flows

Operating Activities

For the year ended December 31, 2022, cash used in operations was $17,846,708 compared to $14,542,592 for the year ended December 31, 2021. The increase in cash used in operations was primarily the result of the increase in net loss offset by a decrease in prepaid expenses and current assets as well as an increase in current liabilities.

Financing Activities

Cash provided by financing activities was $51,329,788 during the year ended December 31, 2021, attributable primarily to net proceeds received from our initial public offering in February 2021 of $15,834,087 and the underwritten offering in September 2021 of $36,999,465, after deducting underwriting discounts and offering expenses. These proceeds were offset by the repayment in full of our RRD Note of $493,480 in February 2021 and repayments of our promissory notes and the unforgiven portion of the PPP Loan of an aggregate of $1,503,764. No financing activities took place during the year ended December 31, 2022.

At December 31, 2022, Virpax had cash of approximately $19.0 million.