On July 11, 2023 ADC Therapeutics reported a voluntary pause in the enrollment of new patients in the Phase 2 LOTIS-9 clinical trial (ClinicalTrials.gov Identifier: NCT05144009) evaluating ZYNLONTA (loncastuximab tesirine-lpyl) and rituximab (Lonca-R) in unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, ADC Therapeutics, JUL 11, 2023, View Source [SID1234634580]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The voluntary action was taken by the Company after a recent review of aggregate data of the 40 patients enrolled in the trial and consultation with the Data Monitoring Committee (DMC) which signaled potentially excessive respiratory-related events. These respiratory-related treatment-emergent adverse events (TEAEs) included seven Grade 5 fatal events and five Grade 3 or Grade 4 respiratory-related TEAEs. As per investigator assessment, eleven of the twelve events (including six of the seven Grade 5 fatal events) were individually assessed as unlikely or unrelated to study drug. Four out of the five Grade 3 or Grade 4 events have since resolved and the patients have completed treatment per protocol. The cause of these events remains under further investigation.

All patients with fatal events had one or more significant active underlying respiratory and/or cardiac co-morbidities including severe chronic obstructive pulmonary disease (COPD), pulmonary edema, chronic bronchiectasis, idiopathic pulmonary fibrosis and recent COVID-19 infection and all were greater than or equal to 80 years of age. The mean age was 82.7 years and the mean number of days from the last dose to death was 51 days, with a range of 19 to 86 days. It is important to note that all twelve of the patients with Grade 3-5 TEAEs in the LOTIS-9 study would have been excluded from the LOTIS-5 trial.

The Company’s decision to pause enrollment enables time to evaluate data around the TEAEs and determine next steps. The Company has notified all study investigators and regulatory authorities including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) of the Company’s decision to pause enrollment. The Company does not expect to report additional data from the trial by the end of the year.

"Our top priority is the safety of every patient who participates in our clinical trials," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "Given the aggregate of the respiratory-related events seen in the trial, we implemented a voluntary pause of enrollment to allow for a thorough investigation of the data set. This trial includes a very difficult-to-treat patient population with limited treatment options, and we will provide an update on next steps when available."

LOTIS-9 Baseline Characteristics, Safety and Efficacy (as of May 10, 2023 data cutoff)

The tables below illustrate preliminary data from the LOTIS-9 clinical trial with a data cut-off date of May 10, 2023. These data are reflective of the 30 patients who were enrolled by that point; since this time an additional 10 patients have enrolled and received treatment as part of the study.

On July 11, 2023 BeiGene reported that on July 10, 2023 BeiGene and Novartis entered into a Mutual Termination and Release Agreement (the "Termination Agreement") to mutually terminate the Option Agreement, effective immediately (Filing, BeiGene, JUL 11, 2023, View Source [SID1234633334]). Pursuant to the Termination Agreement, BeiGene Switzerland regained full, global rights to develop, manufacture and commercialize ociperlimab.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The foregoing description of the terms of the Termination Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Termination Agreement, which the Company intends to file as an exhibit to a subsequent periodic report or on an amendment to this Current Report on Form 8-K.

Item 8.01. Other Events.
The Company will continue the enrollment of the Phase 3 AdvanTIG 302 trial of ociperlimab in combination with its anti-PD-1 antibody tislelizumab for the first-line treatment of patients with locally advanced, unresectable, or metastatic non-small cell lung cancer ("NSCLC") whose tumors exhibit high PD-L1 expression and do not harbor EGFR-sensitizing mutations or ALK translocations. Due to the changing treatment paradigm, the Company will discontinue the Phase 3 AdvanTIG 301 trial of ociperlimab in combination with tislelizumab versus durvalumab following concurrent chemoradiotherapy in patients with stage III unresectable NSCLC. The Company will carefully evaluate all available data to inform future development opportunities with ociperlimab.

On July 11, 2023 Salarius Pharmaceuticals, Inc. (NASDAQ: SLRX), a clinical-stage biopharmaceutical company using protein inhibition and protein degradation to develop cancer therapies for patients in need of new treatment options, reported U.S. Food and Drug Administration (FDA) clearance of the company’s investigational new drug (IND) application to commence a Phase 1 clinical trial with SP-3164 in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) (Press release, Salarius Pharmaceuticals, JUL 12, 2023, View Source [SID1234633199]). Salarius expects to begin treating patients in the dose-escalation portion of the trial in the second half of 2023 to evaluate safety, clinical activity, pharmacokinetics and pharmacodynamics.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"FDA clearance of the SP-3164 IND marks another significant milestone for Salarius and demonstrates our continued focus and commitment to bringing new therapies to patients in need of new treatment options," said David Arthur, president and chief executive officer of Salarius, "We now plan to enroll NHL patients in the dose-escalation portion of the clinical trial and will then focus on patients with diffuse large B-cell lymphoma (DLBCL) in the second portion of the trial."

According to the American Cancer Society, NHL is one of the most common cancers in the U.S., accounting for about 4% of all cancers1. RareDiseaseAdvisor estimates that DLBCL is the most common type of NHL, accounting for approximately 31% of NHL cases in Western countries2.

During the trial, Salarius will be assessing the applicability of the gene signature in predicting response to SP-3164. Previous research with similar agents indicates that patients with an identifiable gene signature may be more likely to respond to SP-3164 treatment. SP-3164 treatment.

Mr. Arthur continued, "More than 80,000 new cases of NHL are expected to be diagnosed in the U.S. in 2023, and even with advances in cancer treatments, more than 20,000 Americans are expected to die from NHL1. We believe SP-3164 may provide an additional treatment option for many of these patients.

"First generation targeted protein degraders (TPD) have generated a great deal of enthusiasm within the pharmaceutical and medical communities, with first-generation TPD’s such as Revlimid and Pomalyst together generating more than $16 billion in 2021 sales. We believe SP-3164, a next generation TPD, can build upon the success of the first-generation TPDs," Mr. Arthur concluded.

About SP-3164

SP-3164 is an oral, next-generation molecular glue that uses Salarius’ deuterium-enabled chiral switching platform to stabilize the preferred (S)-enantiomer of avadomide, an extensively studied clinical compound that has demonstrated encouraging single-agent and combination-therapy clinical efficacy in NHL and other hematologic malignancies. The addition of deuterium at the chiral center of the molecule prevents conversion to the unwanted (R)-enantiomer, allowing for isolation and development of the preferred (S)-enantiomer into a potential new cancer treatment.

As such, SP-3164 is a new chemical entity and has been issued a composition-of-matter patent in the U.S. and select countries around the world. Data presented in December 2022 at the American Society for Hematology Annual Meeting showed compelling SP-3164 activity in lymphoma models and supports SP-3164’s potential for the Phase 1 clinical trial in NHL planned to initiate in 2H 2023. Additional supporting data were presented in April 2023 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting showing SP-3164 demonstrates compelling antitumor activity in animal models of follicular lymphoma and multiple myeloma. Most recently, Salarius presented new data at the European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Conference in Frankfurt, Germany (June 2023) showing SP-3164 induces more degradation of cancer-promoting proteins than the standard-of-care agent lenalidomide (Revlimid).

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.