On October 25, 2021, Oncotelic Therapeutics, Inc. (the "Company") reported that it entered into an Unsecured Convertible Note Purchase Agreement (the "Purchase Agreement") with Golden Mountain Partners, LLC (the ("Holder"), pursuant to which the Company issued a convertible promissory note in the aggregate principal amount of $0.5 million (the "Note"), which Note is convertible into shares of the Company’s common stock, par value $0.01 per share ("Common Stock") (Filing, 8-K, Mateon Therapeutics, OCT 25, 2021, View Source [SID1234592110]).

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The Note carries an interest rate of 2% per annum and matures on the earlier of (a) the one-year anniversary of the date of the Agreement, or (b) the acceleration of the maturity of the Note by Holder upon occurrence of an Event of Default (as defined below). The Note contains a voluntary conversion mechanism whereby the Holder may convert the outstanding principal and accrued interest under the terms of the Note into shares of Common Stock (the "Conversion Shares"), at the consolidated closing bid price of the Company’s Common Stock on the applicable OTC Market as of the date the Company receives a Notice of Conversion (as defined in the Note) from Holder. Prepayment of the Note may be made at any time by payment of the outstanding principal amount plus accrued and unpaid interest. The Note contains customary events of default (each an "Event of Default"). If an Event of Default occurs, at the Holder’s election, the outstanding principal amount of the Note, plus accrued but unpaid interest, will become immediately due and payable in cash. The Purchase Agreement requires the Company to use of the proceeds received under the Note to support the clinical development of OT-101, including payroll and has been made in continuation of the relationship between the Company and the Holder.

The issuance of the Note is exempt from the registration requirements of the Securities Act of 1933, as amended ("Securities Act"), in reliance on the exemptions provided by Section 4(a)(2) of the Securities Act as provided in Rule 506 of Regulation D promulgated thereunder. The shares of Common Stock issuable upon conversion of the Note have not been registered under the Securities Act or any other applicable securities laws, and unless so registered, may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act.

The foregoing descriptions of the Purchase Agreement and the Note are qualified in their entirety by reference to the full text of such agreements, copies of which are attached hereto as Exhibit 10.1 and 10.2, respectively, and each of which is incorporated herein in its entirety by reference.

On October 24, 2021 Orion reported that it will be presenting a video at the LSX’s Inv€$tival Showcase which is being held as a hybrid event with both online and in-person meetings (Press release, Orion Biotechnology, OCT 24, 2021, View Source [SID1234591886]).

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We are looking forward to the forum that directly connects life science companies to global capital and partners. It takes place in London and is held in partnership with global investment bank Jefferies, running the days before the Jefferies London Healthcare Conference.

On October 23, 2021 Applied DNA Sciences, Inc. (ADNAS). a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing and nucleic acid-based technologies, reported that it has signed a mutual collaboration agreement with Ganesha Ecosphere Ltd. (GESL), the largest recycled polyester (rPET) fibre producer in India, to tag an initial pilot production of rPET at GESL’s facilities (Press release, Applied DNA Sciences, OCT 23, 2021, View Source [SID1234591893]).

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Having 3 production facilities in north India, GESL has over 300-plus customers, 250-plus suppliers, and 500-plus product variants. The company produces a wide range of RPSF in white, black and dope dyed colours in solid and hollow conjugated suitable for yarn spinning, nonwovens and fibre fill applications.

On October 23, 2021 OncXerna Therapeutics, Inc. ("OncXerna"), a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates, reported new biomarker data from a retrospective analysis of results from its Phase 1b clinical trial of navicixizumab in an electronic poster at the European Society of Gynaecological Oncology (ESGO) Congress 2021 (Press release, OncXerna Therapeutics, OCT 23, 2021, View Source [SID1234591826]).

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Data presented in the poster are from a retrospective analysis of results from an open-label Phase 1b trial evaluating navicixizumab, a potentially first-in-class anti-DLL4/VEGF bispecific antibody targeting tumor vasculature, in combination with paclitaxel in patients with platinum-resistant ovarian cancer (PROC). Pre-treatment biopsies were analyzed using the investigational Xerna TME Panel to retrospectively compare the biomarker classification of patients against clinical outcomes.

"There is a pressing unmet need for new treatments for patients with platinum-resistant ovarian cancer who have progressed on Avastin or failed more than two lines of prior therapy," said Dr. Kathleen Moore, Stephenson Cancer Center, Oklahoma. "I believe the data presented at ESGO demonstrated the potential of navicixizumab together with the Xerna TME Panel to help address this need. The response rate and treatment durability of navicixizumab in this heavily pretreated patient population are very exciting and results showed improved outcomes in patients classified as having a high angiogenesis score by the Xerna TME Panel’s novel, RNA-expression based algorithm. We have been searching for a predictive biomarker for anti-angiogenic therapies and the Xerna TME panel results presented at ESGO are very promising."

Key data and conclusions from the ESGO poster include:

Clinical outcomes were greater in biomarker positive (B+) vs. biomarker negative (B-) patients
Overall response rate (ORR) in B+ patients: 62% (8/13)
ORR in B- patients: 25% (5/20)
ORR across all patients: 43% (19/44)
Disease control rate (DCR) in B+ patients: 100% (13/13)
DCR in B- patients: 65% (13/20)
DCR across all patients: 77% (34/44)

A consistent correlation was seen between B+ subtype and improved progression-free survival (PFS)
Median PFS in B+ patients: 2 months (95% confidence interval: 5.5 – not estimable)
Median PFS in B- patients: 9 months (95% confidence interval: 1.8 – 8.9)

Laura Benjamin, Ph.D., President and Chief Executive Officer of OncXerna, commented, "The retrospective biomarker analyses presented at ESGO provide an important point of validation for the development of the Xerna TME Panel. Our next step is to further explore these findings through a prospective Phase 3 trial of navicixizumab plus paclitaxel that is also designed to quantify the Xerna TME Panel’s predictive value. We look forward to the initiation of this trial and the evaluation of our Xerna TME Panel as a potential companion diagnostic for immuno-oncology and anti-angiogenic agents."

A copy of the ESGO poster (Abstract 918), entitled: "Correlative analyses of a Phase 1b study of navicixizumab plus paclitaxel in patients with platinum-resistant ovarian cancer using the Xerna TME Panel," can be found here.

About the Phase 1b Trial

The Phase 1b trial was an open-label, non-randomized, dose-escalation and expansion study of the safety, tolerability, and efficacy of navicixizumab plus paclitaxel in patients with platinum-resistant ovarian cancer. The trial enrolled patients who previously received Avastin (bevacizumab) and/or more than 2 prior lines of therapy. Patients were treated with navicixizumab once every two weeks together with weekly paclitaxel. The primary endpoint of the trial was incidence of dose limiting toxicities. Secondary endpoints included response rate assessed by RECIST criteria 1.1 and progression-free survival. For more information, see ClinicalTrials.gov Identifier: NCT03030287.

About Navicixizumab

Navicixizumab is an anti-DLL4/VEGF bispecific antibody product candidate that demonstrated antitumor activity in patients who were previously treated with Avastin (bevacizumab) in a Phase 1b clinical trial. The U.S. Food and Drug Administration granted Fast Track designation to navicixizumab for the treatment of high-grade ovarian, primary peritoneal, or fallopian tube cancer in patients who have previously received Avastin and/or more than 2 prior lines of therapy. Navicixizumab is an investigational agent that has not been approved, and it has not been demonstrated to be safe or effective for any use, including for the treatment of advanced ovarian cancer.

About the Xerna TME Panel

The Xerna TME Panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). The Xerna TME Panel is an investigational assay that has not been approved and has not been demonstrated to be safe or effective for any use.

On October 23, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported the presentation of early clinical data from the ongoing Phase 1/2 CARE study in pediatric and young adult patients with advanced solid tumors harboring ALK, ROS1 or NTRK alterations (Press release, Turning Point Therapeutics, OCT 23, 2021, View Source [SID1234591834]). These data are being presented today at the virtual 53rd Congress of the International Society of Paediatric Oncology (SIOP) being held October 21-24.

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"These early data for repotrectinib demonstrate encouraging clinical activity in this pediatric patient population," said Mohammad Hirmand, M.D., chief medical officer. "Patient enrollment is continuing in the Phase 1/2 CARE study, and we look forward to further advancing the development of repotrectinib in this patient population."

Early Data from Phase 1/2 CARE Study
The primary objective of the Phase 1 dose escalation portion of the study is to evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of repotrectinib in pediatric patients less than 12 years old. The primary objective of the Phase 2 portion of the study is to determine the anti-tumor activity of repotrectinib in pediatric and young adult patients less than 25 years old. Repotrectinib is administrated in capsule or suspension formulation using weight-based dosing for patients less than 12 years old. Patients 12 to 25 years old can enroll directly into the Phase 2 portion of the study with a repotrectinib dose of 160 mg QD for the first 14 days and may increase to 160 mg BID thereafter.

The early Phase 1/2 CARE dataset utilizes an August 2, 2021 data cutoff date. Ten patients were treated across two dose levels. The safety analysis includes the ten treated patients, and the preliminary efficacy analysis includes eight evaluable patients. Patients included in the efficacy analysis had baseline measurable disease and at least one post-baseline evaluable scan. Response evaluation was by physician assessment and per RECIST v1.1 or RANO for CNS tumors. Responses were confirmed with a subsequent scan at least 28 days later.

The findings were reported in a pre-recorded presentation by Steven G. Dubois, M.D., associate professor of Pediatrics, Harvard Medical School available on October 23 at 9:12 a.m. ET on the meeting website.

Preliminary Safety Analysis (n=10) and Pharmacokinetic Analysis

Repotrectinib was generally well tolerated.

The most frequently reported treatment-emergent adverse events (TEAEs) were anemia (n=5) and fatigue (n=5). Among patients with anemia, three had baseline history of anemia.

Dizziness events (n=4) were grade 1 or 2 and none led to treatment discontinuation.

No patients discontinued treatment due to reasons other than disease progression and no patients had TEAEs that led to dose reduction.

No dose-limiting toxicities were reported.

Preliminary pharmacokinetics data indicated that the exposure of repotrectinib in different age groups was comparable to the adult exposure at steady-state.
Preliminary Efficacy Analysis (n=8)

Eight patients were evaluable for efficacy, including four TKI-naïve and four TKI-pretreated patients. TKI-naive patients included those with NTRK amplified anaplastic ependymoma (n=1), NTRK fusion glioblastoma multiforme (GBM)/high grade glioma (n=1), NTRK fusion sarcoma (n=1), and ROS1 fusion inflammatory myofibroblastic tumor (IMT) (n=1). TKI-pretreated patients included those with NTRK fusion GBM/high grade glioma (n=2), NTRK fusion mesoblastic nephroma (n=1), and NTRK fusion sarcoma (n=1).

Three TKI-naïve patients (2 NTRK fusion solid tumors; 1 ROS1 fusion IMT) achieved confirmed responses. One of the three responding patients had a NTRK fusion GBM/high grade glioma, was previously treated with tumor resection, whole brain radiotherapy, and multi-agent chemotherapy, and achieved a complete response (CR) and remained in a response for 3.8+ months as of the data cutoff date. The other two confirmed responders remained in response with duration of response of 7.3+ and 12.1+ months, respectively.

Of the four TKI-pretreated patients, one patient with NTRK fusion sarcoma had a best response of stable disease.
The Phase 1 dose finding portion of the study is ongoing in pediatric patients less than 12 years old to confirm the pediatric RP2D. The Phase 2 portion of the study is ongoing for patients 12 to 25 years old.

Turning Point also announced the publication of preclinical data of repotrectinib in neuroblastoma, the most common pediatric extracranial solid tumor, in the American Association of Cancer Research’s peer reviewed journal, Molecular Cancer Therapeutics. Preclinical studies described in the publication titled "Translational Strategies for Repotrectinib in Neuroblastoma" show that repotrectinib inhibits tumor growth and prolongs survival in patient-derived neuroblastoma xenograft models. In addition, the studies indicated that combining repotrectinib with chemotherapy may be a promising treatment paradigm for neuroblastoma patients.