Entry into a Material Definitive Agreement

On June 29, 2023, Propanc Biopharma, Inc. (the "Company") reported to have entered into a securities purchase agreement (the "Purchase Agreement") with an investor (the "June Investor"), which closed on July 6, 2023, pursuant to which the June Investor purchased a convertible promissory note (the "June Note") from the Company in the aggregate principal amount of $65,000, such principal and the interest thereon convertible into shares of common stock of the Company, par value $0.001 per share (the "Common Stock"), at the option of June Investor at any time after 180 days of the June Note (the "Conversion Shares") (Filing, 8-K, Propanc, JUL 11, 2023, View Source [SID1234633198]). The Company intends to use the net proceeds ($65,000) from the June Note for general working capital purposes.

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The conversion price for the June Note is equal to 65% of the market price of the Common Stock, which is based on the average of the lowest three trading prices of the Common Stock for the ten trading days immediately prior to the delivery of a notice of conversion of the June Note. Notwithstanding the foregoing, such conversions are subject to 4.99% beneficial ownership limitations and adjustments for stock splits, stock dividends or rights offerings, mergers, consolidations, reorganizations and similar events set forth in the June Note. Pursuant to the June Note, the Company is required to maintain an initial reserve of at least 500% of the number of Conversion Shares, subject to any increase of such reserved amount by the Investor (the "Reserve Amount").

The maturity date of the June Note is June 29, 2024 and bears interest at a rate of 8% per annum, which may be increased to 22% in the event of a default. During the first 60 days following the date of the June Note, the Company has the right to prepay the principal and accrued but unpaid interest due under the June Note issued, together with any other amounts that the Company may owe the June Investor under the terms of the June Note, at a 110% premium of the face amount plus accrued and unpaid interest and any other amounts owed to the June Investor, which increases to (i) 115% if prepaid after 60 days, but less than 91 days from the issuance date, (ii) 120% if prepaid after 90 days, but less than 121 days from the issuance date, (iii) 125% if prepaid after 120 days, but less than 151 days from the issuance date, and (iv) 129% if prepaid after 150 days, but less than 181 days from the issuance date. After this initial 180-day period, the Company does not have a right to prepay the June Note. Additionally, pursuant to the June Note, so long as the June Note is outstanding, the Company agreed not to sell, lease or otherwise dispose of all or substantially all of its assets outside the ordinary course of business which would render the Company a "shell company" as defined in Rule 144 of the Securities Act, as amended (the "Securities Act"), without the June Investor’s consent.

The June Note contains certain events of default, including failure to timely issue the Conversion Shares, failure to maintain the listing of the Common Stock on at least one of the OTC markets (which specifically includes the quotation platforms maintained by the OTC Markets Group) or an equivalent replacement exchange, failure to comply with its reporting requirements under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), a default by the Company under any other agreements entered into with the June Investor, as well as certain customary events of default set forth in the June Note, including, among others, breach of covenants, representations or warranties, insolvency, bankruptcy, liquidation and failure by the Company to pay the principal and interest due under the June Note. Upon an event of default, the June Note will become immediately due and payable by the Company in an amount equal to 150% of an amount equal to the then outstanding principal amount of the June Note plus any interest accrued upon such event of default or prior events of default.

July Loan Agreement

On July 5, 2023, the Company and an institutional investor (the "July Investor") entered into a letter agreement (the "Loan Agreement"), pursuant to which the July Investor loaned the Company an aggregate of AU$230,000. Pursuant to the Letter Agreement, the term of such loan is three (3) years, ending on July 5, 2026, with an interest rate of 10% to be paid monthly in arrears. A portion of the proceeds of such loan were used to repay an outstanding balance of approximately $143,000 due on a convertible promissory note held by a third-party investor and which was currently in default. In connection with such loan, the Company issued a common stock purchase warrant (the "Warrant") to the July Investor immediately exercisable for up to an aggregate of 15,000,000 shares of Common Stock, at an initial exercise price of $0.01 per share. The Warrant contains a 4.99% beneficial ownership limitation and adjusts for stock splits, dividends, rights offerings and similar events, and is exercisable for three years from the date of its issuance.

The foregoing descriptions of each of the Purchase Agreement, the June Note, the Loan Agreement and the Warrant do not purport to be complete and are qualified in their entirety by reference to the full text of each of the Purchase Agreement, the June Note, the Loan Agreement and the Warrant, which are filed as Exhibits 10.1, 4.1, 10.2 and 4.2, respectively, to this Current Report on Form 8-K (this "Form 8-K") and are incorporated herein by reference.

Stanford University Joins Cofactor Genomics’ Clinical Trial Evaluating Immunotherapy Predictive Diagnostic Assay Across 11 Cancers

On July 11, 2023 Stanford University and Cofactor Genomics, the company bridging the precision medicine gap, reported that Stanford will join Cofactor’s PREDAPT (Predicting Immunotherapy Efficacy From Analysis of Pre-treatment Tumor Biopsies) ​​clinical trial evaluating use of the company’s OncoPrism predictive diagnostic assay across 11 cancers (Press release, Stanford University, JUL 11, 2023, View Source [SID1234633186]). Cofactor’s patented approach to building multidimensional immune biomarkers powers OncoPrism, which has been shown to predict tumor response to immunotherapy with almost twice the accuracy of PD-L1 tests.

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Stanford University joins more than 20 healthcare and hospital systems currently enrolling patients in the PREDAPT Trial with an approved protocol to study OncoPrism in patients with 11 types of cancer, including triple-negative breast, cervical, colorectal, esophageal, gastric, head and neck, kidney, liver, lung, and urothelial cancers. Immunotherapies produce durable and lasting results for a subpopulation of patients, but currently available diagnostics powered by single-analyte biomarkers are not sufficient at identifying who will benefit from the drugs. More advanced predictive diagnostics like OncoPrism are more robust and better at helping physicians determine a patient’s a treatment path that includes immunotherapy and avoids the toxicities of treatments like chemotherapy.

"Improving our ability to predict which patients will respond to which immunotherapies is key to helping us match the right treatment to the right patient at the right time," said A. Dimitrios Colevas, MD, Professor of Oncology and of Radiation Oncology at Stanford Cancer Center, "We have excellent immunotherapies available, but today’s diagnostic tools are limited in identifying all of the patients that can benefit. We are excited to join the PREDAPT study and explore how new predictive diagnostics may be able to help us connect more patients with powerful drugs that can help them."

"The addition of Stanford University to the impressive list of clinical partners participating in the PREDAPT trial validates the potential of our predictive diagnostic approach to accelerate therapeutic matchmaking, getting patients the right drugs more quickly and thereby improving, and even extending, their lives," said Cofactor Genomics CEO Jarret Glasscock.

Hummingbird Diagnostics Announces Publication of miLung Small RNA-Based Blood Test for Early Detection of Lung Cancer in the Journal of Thoracic Oncology

On July 11, 2023 Hummingbird Diagnostics GmbH, a leader in reading blood-based small RNAs for early disease detection and characterization, reported a publication in the Journal of Thoracic Oncology following a poster presentation at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting on the miLung small RNA blood test for early-stage lung cancer detection (Press release, Hummingbird Diagnostics, JUL 11, 2023, View Source [SID1234633185]).

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The results of the study provide clear evidence for the viability of a small RNA-based blood test as an alternative to low-dose computed tomography (LDCT) screening, which could be deployed in a primary care setting for early-stage lung cancer detection. Screening was performed on stabilized whole blood samples from 1,384 individuals meeting National Lung Screening Trial (NLST) lung cancer eligibility criteria (age 55-74, pack-years ≥30) by leveraging ultra-deep small RNA sequencing. A newly discovered 18-small RNA signature (miLung) was validated as a molecular biomarker for lung cancer in an independent cohort of 441 individuals1. The miLung small RNA blood test is noninvasive and identifies specific small RNAs, molecular biomarkers associated with lung cancer in whole blood samples that can be drawn at the point of care.

"We have developed a sensitive yet robust analysis using small RNA tumor markers to detect early-stage lung cancer," remarked Bruno Steinkraus, PhD, Chief Scientific Officer of Hummingbird Diagnostics. "Our approach integrates tumor-derived and immune system-derived small RNAs into unbiased machine learning to inform early-stage lung cancer detection."

The multicenter study was performed in collaboration with Dr. Amita Sharma at Massachusetts General Hospital, Professor Alexander Bankier at Beth Israel Deaconess Medical Center, Professor Martin Reck at LungenClinic Grosshansdorf, Professor Clemens Aigner of University Medicine Essen and Professor Klaus Rabe of LungenClinic Grosshansdorf amongst others.

"Early cancer detection remains the most effective strategy to reduce mortality associated with lung cancer," commented Jochen Kohlhaas, Founder and Chief Executive Officer of Hummingbird Diagnostics. "We envision the miLung test as a non-invasive alternative to LDCT scans for use in primary care settings to improve participation in screening, and potentially reduce gender- and race-based disparities in access to lung cancer screening."

The ASCO (Free ASCO Whitepaper) poster presentation titled "Early detection of lung cancer using small RNAs" can be found here.

The article can be found on the Journal of Thoracic Oncology’s website here.

1 Sikosek T and Horos R et al. Early Detection of Lung Cancer using small RNAs. Journal of Thoracic Oncology (2023), doi: View Source

MAIA Biotechnology Reports Updates on Disease Control Rates for THIO-101 Phase 2 Trial for Advanced Non-Small Cell Lung Cancer

On July 11, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA) reported updates on disease control data in the Part A safety lead-in of its ongoing THIO-101 phase 2 trial, evaluating THIO in sequential combination with cemiplimab in patients with advanced Non-Small Cell Lung Cancer (NSCLC) (Press release, MAIA Biotechnology, JUL 11, 2023, View Source [SID1234633184]).

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Of the first 11 patients enrolled in THIO-101 to complete at least 1 post baseline response assessment, 9 (82%) met the primary endpoint of disease control (defined as a Complete Response, Partial Response, or Stable Disease per RECIST 1.1). All patients enrolled have previously failed 2 or more prior lines of treatment including an immune checkpoint inhibitor (CPI) and platinum-based chemotherapy for advanced NSCLC. No new safety analysis was conducted at this time.

"The 82% disease control rate observed so far with this combination is highly encouraging, especially in the heavily pre-treated population with previous immune CPI resistance, where typically the Disease Control Rates are in the 25-35% range. This preliminary data aligns with our pre-clinical data which showed that THIO, followed by an immune checkpoint inhibitor, greatly slowed and reduced tumor progression when compared to treatment with CPI alone. We look forward to continue the monitoring of these patients and evaluate disease control rates on a longer time frame with the next response assessment phases," said Vlad Vitoc, MAIA’s Chief Executive Officer.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is an investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s potential immune system activation effects in NSCLC patients by administering THIO in sequential combination with Regeneron’s anti-PD1 therapy, Libtayo (cemiplimab), allowing for immune activation and PD-1 sensitivity to take effect. The trial will test the hypothesis that low doses of THIO administered prior to a checkpoint inhibitor will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer agent and a priming immune system agent (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

IconOVir Bio Announces First Patient Dosed in Phase 1 Clinical Trial of its Lead Product Candidate, ICVB-1042

On July 11, 2023 IconOVir Bio, Inc. (IconOVir), a clinical-stage biotechnology company pioneering the next generation of oncolytic virus (OV) therapy to improve the treatment of patients with cancer, reported that the first patient has been dosed in a Phase 1 dose escalation and expansion clinical trial evaluating intravenously (IV) administered ICVB-1042 for the treatment of advanced solid tumors (Press release, IconOVir Bio, JUL 11, 2023, View Source [SID1234633183]).

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"We are delighted to begin clinical evaluation of ICVB-1042, our potentially best-in-class OV and the first product candidate to emerge from our portfolio," said Mark McCamish, M.D., Ph.D., President and Chief Executive Officer of IconOVir. "We founded IconOVir to pioneer the next generation of OVs to improve the care and treatment of people living with solid tumors, with the ultimate mission of curing cancer and restoring life to patients everywhere. The initiation of this Phase 1 trial marks an important step toward achieving that goal and I look forward to working with our clinical partners to enroll and execute this study."

ICVB-1042 is a chimeric oncolytic adenovirus, rationally designed with genomic modifications to confer tumor selective replication, broad tropism and enhanced tumor cell killing, as well as allow for either IV or intratumoral delivery. In preclinical studies, ICVB-1042 has been shown to infect and kill a broad range of tumor cells, including head and neck, bladder, lung and breast, suggesting that it could have potential utility in a wide range of solid tumor indications.

"Leveraging our proprietary platforms, we engineered and combined novel mutations to create ICVB-1042, the first OV with the potential to be delivered systemically, without sacrificing potency or tumor selectivity," said Julie Maltzman, M.D., Chief Medical Officer of IconOVir. "Preclinical data suggest that ICVB-1042 offers a highly differentiated profile relative to currently marketed or OVs in development, which may translate into more effective anti-cancer activity across a range of difficult-to-treat tumors. We expect to know from early data whether ICVB-1042 can be effectively delivered IV to drive viral replication in the tumor, which would provide strong mechanistic support for our approach. We look forward to reporting initial safety data later this year, with potential biological proof-of-concept in the first half of 2024 and we are pleased that our first patient tolerated ICVB-1042 therapy well."

About the Phase 1 Clinical Trial

IconOVir’s Phase 1 clinical trial is an open-label study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and biological and clinical activity of ICVB-1042 in patients with relapsed or refractory solid tumors. The goal of the study is to establish a maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D). Once the MTD is reached, or a RP2D is established, IconOVir intends to open expansion cohorts in advanced solid tumors. Biological activity will be measured by viral replication in the tumor. Clinical response will be assessed by immune Response Evaluation Criteria in Solid Tumors (iRECIST) version 1.1. To learn more about the first-in-human trial of ICVB-1042, please visit www.clinicaltrials.gov (NCT05904236).