Entry into a Material Definitive Agreement

On December 9, 2021, Oncotelic Therapeutics, Inc. (the "Company") reported that it entered into a Securities Purchase Agreement (the "Purchase Agreement") with FirstFire Global Opportunities Fund, LLC (the ("Holder"), pursuant to which the Company issued a convertible promissory note in the aggregate principal amount of $0.25 million (the "Note") (Filing, 8-K, Mateon Therapeutics, DEC 9, 2021, View Source [SID1234597199]). On December 12, 2021, the Company entered into a Securities Purchase Agreement (the "Blue Lake Purchase Agreement") with Blue Lake Partners, LLC ("Blue Lake"), pursuant to which the Company issued a convertible promissory note in the aggregate principal amount of $0.25 million (the "Blue Lake Note"). Further on December 15, 2021, the Company entered into a Securities Purchase Agreement (the "Fourth Man Purchase Agreement", and collectively with the Purchase Agreement and the Blue Lake Purchase Agreement, the "Purchase Agreements"), with Fourth Man, LLC ("Fourth Man"), pursuant to which the Company issued a convertible promissory note in the aggregate principal amount of $0.25 million (the ‘Fourth Man Note", and collectively with the Note and the Blue Lake Note, the "Notes"). The Notes are convertible into shares of the Company’s common stock, par value $0.01 per share ("Common Stock").

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The Purchase Agreements and the Notes were entered into as part of a convertible note financing round with aggregate gross proceeds to the Company of up to $1.25 million (the "Financing"), undertaken by the Company pursuant to that certain Finder’s Fee Agreement between the Company and JH Darbie & Co., Inc. ("JH Darbie"), dated October 26, 2021 (the "Agreement"). Pursuant to the Agreement, JH Darbie will be entitled to a finder’s fee of: (a) 10% of the gross proceeds received by the Company in cash; and (b) warrants equal 10% warrant coverage of the amount raised, with a purchase price equal to the Conversion Price, with such warrants to expire five years from the date of issuance. The issuance and sale of the Notes on December 9, 2021, December 12, 2021 and December 15 2021, respectively, represented the third, fourth and fifth tranches of the Financing, totaling a gross of $0.75 million, for an aggregate gross total of $1.25 million across the five tranches. The Purchase Agreements and the Notes contain identical terms to the securities purchase agreements (and promissory notes issued thereunder), to Talos Victory Fund, LLC on November 24, 2021 and Mast Hill Fund, LP on November 30, 2021 (the "Prior Issuances"), except with reference to the name of the holders, the use of proceeds, which include repayment of certain debt, general corporate expenses and payroll, as applicable, and the law governing the terms of the Prior Issuances. The Prior Issuances were previously reported on our Current Report on Form 8-K filed with the Securities and Exchange Commission ("SEC") on December 1, 2021.

The Notes carry an interest rate of 12% per annum and matures on the earlier of (a) the one-year anniversary of the date of the Purchase Agreements, or (b) the acceleration of the maturity of the Notes by the applicable holder upon occurrence of an Event of Default (as defined below). The Notes contain a voluntary conversion mechanism whereby the applicable holder may convert the outstanding principal and accrued interest under the terms of the Notes into shares of Common Stock (the "Conversion Shares"), at a fixed price of $0.07 per share (the "Conversion Price"), subject to adjustments upon the occurrence of certain corporate events. Prepayment of the Notes may be made at any time upon three trading days’ prior written notice to the respective holder, by payment of the then outstanding principal amount plus accrued and unpaid interest and reimbursement of such holder’s administrative fees. The Notes contains customary events of default (each an "Event of Default"). If an Event of Default occurs, at the respective holder’s election, the outstanding principal amount of the Notes, plus accrued but unpaid interest, will become immediately due and payable in cash. The Purchase Agreements require the Company to use the proceeds for general working capital, and not for (i) the repayment of any indebtedness owed to officers, directors or employees of the Company or their affiliates, (iii) any loan to or investment in any other corporation, partnership, enterprise or other person (except in connection with the Company’s currently existing operations), (iv) any loan, credit, or advance to any officers, directors, employees, or affiliates of the Company, or (v) in violation or contravention of any applicable law, rule or regulation.

The issuance of the Notes are 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. The shares of Common Stock issuable upon conversion of the Notes 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 Agreements and the Notes are qualified in their entirety by reference to the full text of the form of such agreements, copies of which were attached as Exhibit 10.1 and 10.2, respectively, and the Agreement, attached as Exhibit 10.3, with our Current Report on form 8-K filed with the SEC on December 1, 2021 and each of which is incorporated herein in its entirety by reference.

iOnctura Presents Positive Clinical Data At ESMO-IO Supporting Advancement of IOA-289, a Novel Autotaxin Inhibitor, Into Phase Ib Pancreatic Cancer Studies

On December 9, 2021 iOnctura SA, a clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface, reported clinical data confirming the mode of action of its autotaxin inhibitor IOA-289 and showing preclinical evidence of the role of autotaxin inhibition in breaking down tumor resistance mechanisms (Press release, iOnctura, DEC 9, 2021, View Source [SID1234640237]). IOA-289 will be the first autotaxin inhibitor to be clinically investigated in oncology. The data will be presented as a poster at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s Immuno-Oncology Congress (ESMO-IO) taking place on December 8–11, 2021 as a virtual meeting.

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The randomized, double-blind, placebo-controlled study of single ascending doses of IOA-289 showed that IOA-289 lowered circulating levels of LPA in a dose-dependent manner. LPA is a blood-based biomarker of autotaxin inhibition; importantly, LPA levels have been shown to correlate with circulating CA19-9, a clinical biomarker of pancreatic cancer progression, providing a strong rationale for a biomarker-evaluable-response in this study. A Phase I clinical study of IOA-289 in pancreatic cancer, a malignancy typically characterized by a fibrotic and immune excluded phenotype, is in preparation.

Further compelling preclinical data show IOA-289 reduces tumor burden in mouse pancreatic cancer models. The experimental results support the role of cancer-associated fibroblasts (CAFs) in promoting pancreatic adenocarcinoma cells (PDAC) growth. Additionally in preclinical models iOnctura has demonstrated that blocking autotaxin reduces fibrosis and enhances recruitment of T effector cells, two key mechanisms driving tumor mediated resistance to cancer therapy.

The poster presentation at ESMO (Free ESMO Whitepaper)-IO is entitled "Translating a novel autotaxin inhibitor from preclinical proof of concept in pancreatic cancer to a biomarker response in human subjects" (P131).

The e-poster presentation is available on the ESMO (Free ESMO Whitepaper)-IO virtual meeting platform and iOnctura’s website.

Contacts

iOnctura
Catherine Pickering
Chief Executive Officer
T : +41 79 952 72 52
E: [email protected]

Press Relations
Jeremy Nieckowski
LifeSci Advisors
T: +41 79 699 97 27
E: [email protected]
iOnctura SA is clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface. iOnctura’s best-in-class drug development programs combine immune-mediated and direct anti-tumor activity to deliver molecules with superior clinical efficacy and safety in oncology. Its lead program, IOA-244 is the only semi-allosteric PI3Kdelta specific, orally dosed, small molecule inhibitor that is being developed in solid and hematological malignancies to address tumor and stroma induced immune suppression. IOA-244 is currently in Part B of a Phase 1 study. iOnctura’s second program, IOA-289, is an oral small molecule that inhibits the cross-talk between the tumor and its stroma and is in a Phase 1 clinical study. iOnctura is backed by blue chip investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, and 3B Future Health Fund. For more information, please visit iOnctura’s website.

IOA-289, originally licensed from Cancer Research UK, is iOnctura’s second clinical compound, a next generation oral small molecule autotaxin inhibitor that is currently being investigated in the healthy volunteer stage of the AION 01 trial (ClinicalTrials.gov Identifier: NCT05027568). A phase 1 clinical study in pancreatic cancer patients is in preparation. iOnctura has undertaken extensive validation of the autotaxin inhibition mechanism in multiple solid tumor preclinical models.

Pancreatic cancer (PDAC): Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer accounting for approximately 90% of cases. PDAC has a poor prognosis, with less than 5% of patients surviving beyond five years after diagnosis. Pancreatic cancer accounts for about 3% of all cancers in the US and about 7% of all cancer deaths, with 60,430 diagnoses each year in the United States and 48,220 deaths.

HALOZYME ANNOUNCES $750 MILLION THREE-YEAR SHARE REPURCHASE PROGRAM

On December 9, 2021 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that its Board of Directors has approved a new share repurchase program effective immediately, which authorizes the Company to purchase up to $750 million of the Company’s outstanding common stock over the next three years (Press release, Halozyme, DEC 9, 2021, View Source [SID1234596698]). The Company plans to enter into an accelerated share repurchase (ASR) program transaction with a financial institution in the coming week, subject to market conditions. The Company plans to purchase up to $250 million worth of shares by the end of 2022, including the $150 million ASR, pending market conditions and other factors.

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"Our second share repurchase authorization demonstrates Halozyme’s commitment to a balanced capital allocation strategy that includes investing in our operations, capital return and potential M&A," said Dr. Helen Torley, president and chief executive officer. "We are pleased that our strong cash generation and balance sheet enables us to return capital to investors while maintaining our ability to invest in our future to sustainably grow our business."

This share repurchase program follows the recent completion of the Company’s prior $550 million three-year share repurchase program, which was completed in less than two years.

The amount and timing of shares repurchased under the share repurchase program will be subject to a variety of factors including market conditions, other business considerations and applicable legal requirements. Repurchases may be commenced or suspended at any time or from time-to-time at the Company’s discretion without prior notice. Repurchases may be made through both public market and private transactions. The Company plans to fund repurchases from its existing cash balance. The Company’s Board of Directors will regularly review this capital return policy in connection with a balanced capital allocation strategy focused on funding growth.

Ascentage Pharma and Clover Biopharmaceuticals Announce Clinical Collaboration to Evaluate IAP Antagonist, APG-1387, plus the Recombinant Human TRAIL-Trimer Fusion Protein, SCB-313, for the Treatment of Peritoneal Carcinomatosis

On December 9, 2021 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has entered into a clinical collaboration with Clover Biopharmaceuticals, Ltd. ("Clover"; Stock Code: 2197.HK) to evaluate Ascentage Pharma’s APG-1387, a second mitochondria-derived activator of caspase (SMAC)-mimetic/inhibitor of apoptosis proteins (IAP) antagonist, in combination with Clover’s SCB-313, a recombinant human TRAIL-trimer fusion protein, in a Phase Ib/II study in patients with advanced peritoneal carcinomatosis (Press release, Ascentage Pharma, DEC 9, 2021, View Source [SID1234596720]).

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Ascentage Pharma and Clover will jointly conduct this open-label, multicenter, Phase Ib/II study to evaluate the safety, tolerability, pharmacokinetics/ pharmacodynamics (PK/PD), and efficacy of APG-1387 in combination with SCB-313 for the treatment of patients with primary or secondary peritoneal carcinomatosis from different primary tumor origins in China and Australia.

Discovered and developed by Ascentage Pharma, APG-1387 is a potent and highly specific next-generation IAP antagonist and the first IAP antagonist entering clinical development in China. To advance the clinical development of APG-1387 globally, Ascentage Pharma has completed a Phase I dose-escalation for the treatment of solid tumors in China and Australia, and is currently conducting multiple clinical studies of APG-1387 combinations for the treatment of solid tumors in China and the US. Meanwhile, APG-1387 is also being evaluated in a Phase II study in patients with chronic hepatitis B (HBV) infections in China.

Clover’s SCB-313 is a trimeric fusion protein in clinical development for the treatment of intracavitary malignancies. Based on positive Phase I interim analyses, Clover plans to advance SCB-313 into a Phase II clinical trial for malignant ascites in the first half of 2022. SCB-313 is also in Phase I clinical trials for malignant pleural effusions and peritoneal carcinomatosis. Clover also plans to initiate new Phase I trials for SCB-313 in new indications, such as bladder cancer, in 2022.

"Safe and effective combination therapies represent an increasingly important approach in cancer treatment. We hope APG-1387 in combination with Clover’s SCB-313 will demonstrate synergistic effect," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "We look forward to working closely with Clover to advance this clinical collaboration which hopefully will offer a new treatment option to patients with peritoneal carcinomatosis."

"Clover is excited to enter into this partnership with Ascentage Pharma to explore innovative treatment options and alternatives to surgery for patients suffering from peritoneal carcinomatosis," said Joshua Liang, Chief Executive Officer of Clover Biopharmaceuticals. "Combination treatment is a cornerstone of cancer therapy. By targeting different nodes within the apoptosis pathway, we believe the combination of SCB-313 and APG-1387 could provide a synergistic benefit to patients."

About APG-1387

Discovered and developed by Ascentage Pharma, APG-1387 is a potent and highly selective next-generation inhibitor of apoptosis proteins (IAP) antagonist that can degrade IAPs by mimicking endogenous second mitochondria-derived activator of caspase (SMAC) molecule to induce programmed cell death or apoptosis. To advance the clinical development of APG-1387 globally, Ascentage Pharma has already completed a Phase I dose-escalation study in patients with solid tumors in China and Australia, and is currently conducting a Phase Ib/II clinical study of the APG-1387 plus pembrolizumab combination in patients with solid tumors in the US, and a Phase Ib/II study of APG-1387 plus nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer in China. Moreover, APG-1387 is also being evaluated in a Phase II study in patients with chronic hepatitis B (HBV) infections in China.

About SCB-313

SCB-313, an innovative, recombinant human TNF-related apoptosis-inducing ligand (TRAIL)-Trimer fusion protein engineered using the Trimer-Tag technology platform to target the extrinsic apoptosis pathway. Binding of SCB-313 to the death receptors (DR4 and DR5) leads to physiologic trimerization and potent activation of the extrinsic apoptosis pathway.

HiberCell to Present Clinical Applications of Odetiglucan and the Role of Beta-Glucan in Cancer Treatment at ESMO Immuno-Oncology Virtual Congress 2021

On December 9, 2021 HiberCell, a clinical-stage biotechnology company developing therapeutics to address therapeutic resistance, cancer relapse and metastasis, reported that it will deliver a virtual presentation on the clinical applications of our odetiglucan (Imprime PGG) therapy for patients with metastatic and late-stage cancer at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Virtual Congress 2021, December 8-11, 2021 (Press release, HiberCell, DEC 9, 2021, View Source;utm_medium=rss&utm_campaign=hibercell-to-present-clinical-applications-of-odetiglucan-and-the-role-of-beta-glucan-in-cancer-treatment-at-esmo-immuno-oncology-virtual-congress-2021 [SID1234596646]).

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This 20-minute presentation will focus on the broad applicability of odetigulcan in combination with different therapeutic agents and across multiple cancers.

Title: Beta-glucan in cancer treatment
Presenter: Nandita Bose, Ph.D., Senior Vice President of Clinical and Translational Medicine, HiberCell
Session: Trained Immunity Educational Session
Time/Date: Saturday, December 11, 2021: 10:00 – 10:20 am CT
Odetiglucan is a Dectin-1, pattern recognition receptor agonist that is currently in a phase 2 clinical trial in combination with pembrolizumab, an anti-programmed death receptor-1 (PD-1) used in cancer immunotherapy, for the treatment of metastatic, hormone-refractory breast cancer patients. The World Health Organization assigned "odetiglucan" as the International Nonproprietary Name (INN) for Imprime PGG as of November 2021.

For more information about HiberCell’s clinical trials, visit the website at www.HiberCell.com.