2022 – Page 2469 – 1stOncology™: Cancer Intelligence Service

Clarity advances to cohort 2 in the SARTATE™ neuroblastoma trial

On February 1, 2022 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical-stage radiopharmaceutical company developing next-generation products to address the growing needs in oncology, reported that it has completed cohort 1 and advanced to cohort 2 in the 64Cu/67Cu SARTATE Neuroblastoma trial (CL04 trial) (Press release, Clarity Pharmaceuticals, FEB 1, 2022, View Source [SID1234607517]).

The SRC assessed the data from cohort 1 in three patients where no DLTs have occurred and recommended to progress the trial to cohort 2, without modification, increasing the dose from 75MBq/kg to 175MBq/kg body weight. Additional therapy cycles of 67Cu SARTATE have been requested by clinical sites and are being administered to patients in cohort 1 in the CL04 trial. As part of the trial, patients have also received multiple doses of 64Cu SARTATE for the imaging of tumours to assess disease localisation and eligibility for therapy. At the time of the SRC meeting, no adverse events had been reported relating to the administration of 64Cu-SARTATE.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are very excited to successfully advance our SARTATE product in neuroblastoma, having completed cohort 1 of this therapy trial with 67Cu SARTATE. Dosing patients at 75MBq/kg body weight in cohort 1 of the CL04 trial enabled us to generate initial data to assess the safety profile along with some initial efficacy data for this product. We look forward to progressing the trial at some of the leading cancer centres in the U.S at the increased dose level of 175MBq/kg body weight, which we hope will build upon the mounting diagnostic and therapeutic benefits of this theranostic product and improve the treatment paradigm for children with this insidious disease."

The CL04 trial is a theranostic (diagnosis and therapy) trial in paediatric patients with high-risk neuroblastoma (NCT04023331)1. It is a multi-centre, dose-escalation, open label, non-randomised, Phase 1/2a clinical trial with up to 34 patients conducted at five clinical sites in the US.

Neuroblastoma most often occurs in children younger than 5 years of age and presents when the tumour grows and causes symptoms. It is the most common type of cancer to be diagnosed in the first year of life and accounts for around 15% of paediatric cancer mortality.2 High-risk neuroblastoma accounts for approximately 45% of all neuroblastoma cases. Patients with high-risk neuroblastoma have the lowest 5-year survival rates at 40%-50%.3

In 2020, the US Food and Drug Administration (FDA) awarded Clarity two Orphan Drug Designations (ODDs), one for 64Cu SARTATE as a diagnostic agent for the clinical management of neuroblastoma and one for 67Cu SARTATE as a therapy of neuroblastoma, as well as two Rare Paediatric Disease Designations (RPDDs) for these products. Should Clarity be successful in achieving US FDA New Drug Applications for these two products, RPDDs may potentially allow the Company to access a total of two tradeable Priority Review Vouchers (PRVs) which most recently traded at USD110M per voucher.4

Dr Taylor said, "The support and persistence we have experienced throughout the neuroblastoma trial to date from our numerous supporters, such as the clinical sites, Clarity’s team, our collaborators and the US FDA, is indicative of the importance and urgency of improving the prognosis of children with high-risk neuroblastoma, where current treatment strategies are limited. Despite the challenges we faced during the pandemic, which had a significant impact on clinical site operations and management, as well as recruitment hurdles in the US, we continue to progress this trial with increased determination and fervour to ensure we achieve our ultimate goal of improving treatment outcomes for children and adults with cancer."

This announcement has been authorised for release by the Executive Chairman.

First patient dosed in Biocity CD3/EGFR BsAb BC3448 trial

On January 26th, 2022 Wuxi, Shanghai, and Shijiazhuang—BioCity, a clinical-stage Chinese biopharmaceutical company, reported the dosing of its first test subject in the Phase I clinical trial of BC3448 (CD3/EGFR bispecific antibody, BsAb) (Press release, Biocity Biopharmaceutics, JAN 31, 2022, View Source [SID1234633309]).

The trial is a Phase I, open-label, first in-human dose-escalation and -expansion clinical trial evaluating the safety、tolerability、phar-macokinetic characteristics, and pre-liminary efficacy of BC3448 in patients with locally advanced or metastatic malignant solid neo-plasms. The primary objective of the study is to evaluate the safety and tolerability of BC3448 monotherapy in patients with ad-vanced solid tumors.

BC3448 is a CD3/EGFR bispecific antibody that activates T cells to kill tumors cells with EGFR expression. In preclinical in vitro and in vivo studies, BC3448 demonstrated antitumor activities regardless of the mutation status of EGFR, KRAS or BRAF genes.

Professor Caicun Zhou, Director of the Oncology Department at Shanghai Pulmonary Hospital, affiliated to Tongji University, and Director of the Tongji University School of Medicine’s Cancer Institute, stated that, " although there have been breakthroughs in the EGFR-targeted drugs including monoclonal antibodies and EGFR TKIs, challenges remain for patients after their tumors developed resistance to the available EGFR antibodies or TKIs.

Therefore, there is need to explore new approaches such as immunotherapy drugs to deal with the issues of resistance to the available EGFR-targeted agents. The CD3-based EGFR-targeting bispecific antibody BC3448 holds great promise to treat EGFR-expression tumors even after resistance to the current EGFR therapies."

The Co-CEO of Biocity, Dr. Yong jiang Hei said, "BC3448 is a CD3/EGFR bispecific antibodies designed to have a stronger binding affinity for EGFR than that for CD3, which may help re-duce the risk of cytokine release syndrome (CRS), a known safety issue associated with CD3-based bispecific antibodies.

Currently, few companies have CD3/EGFR bispecific antibodies in clinical development globally, and BC3448 is one of the leading programs in this area. We strive to accelerate the clinical development of this innovative molecule in order to better meet the unmet medical needs for patients around the world."

About BC3448

BC3448 is a CD3/EGFR bispecific anti-body independently developed by BioCity, with IND approval from the National Medical Products Administration(NMPA). It is undergoing active clinical development in China.

Elusys Therapeutics Finalizes HHS Contract to Deliver ANTHIM®, Its Treatment for Inhalation Anthrax, to the U.S. Department of Health and Human Services

On January 31, 2022 Elusys Therapeutics, Inc. (Elusys) reported that it has finalized a contract with the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services (HHS) for the continued supply of ANTHIM (obiltoxaximab), an anthrax antitoxin, for use against a potential anthrax attack (Press release, NightHawk Biosciences, JAN 31, 2022, View Source [SID1234612541]).

"Elusys is pleased to continue its successful track record of supplying a critical medicine to treat the deadly effects of anthrax exposure," said Elizabeth Posillico, president and chief executive officer of Elusys. "ANTHIM is a key therapeutic in the U.S. government’s preparedness strategy to protect the U.S. population against natural and man-made biothreats."

The contract for the procurement of ANTHIM consists of a base period of performance, valued at $50 million, which has been fulfilled. The contract includes options valued up to $31 million. If all options are exercised, the total contract value will be $80,864,000 with completion of the contract expected by the first half of 2023. Contract 75A50121C00073 is funded by HHS ASPR.

As previously announced, Elusys has executed a definitive merger agreement with Heat Biologics, Inc. (NASDAQ: HTBX), pursuant to which Elusys will merge into a wholly owned subsidiary of Heat. The acquisition is expected to close during the first quarter of 2022 and is subject to customary closing conditions.

About ANTHIM
ANTHIM is a monoclonal antibody that binds to the protective antigen (PA) component of anthrax toxin. ANTHIM’s toxin neutralizing activity prevents entry of anthrax toxin into susceptible cells, avoiding further spread of the toxin throughout the body and the ensuing tissue damage that leads to death. ANTHIM is supplied as single-dose vials for IV infusion.

ANTHIM is indicated in adult and pediatric patients for the treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. ANTHIM should only be used for prophylaxis when its benefit for prevention of inhalational anthrax outweighs the risk of hypersensitivity and anaphylaxis. The effectiveness of ANTHIM is based solely on efficacy studies in animal models of inhalational anthrax. There have been no studies of the safety or pharmacokinetics (PK) of ANTHIM in the pediatric population. Dosing in pediatric patients was derived using a population PK approach. ANTHIM does not have direct antibacterial activity. ANTHIM should be used in combination with appropriate antibacterial drugs. ANTHIM is not expected to cross the blood-brain barrier and does not prevent or treat meningitis.

Anthrax is a life-threatening infectious disease caused by Bacillus anthracis. Cases of inhalational anthrax in humans can occur through intentional spread of B. anthracis spores as a biowarfare or bioterrorism agent. B. anthracis spores introduced through the lungs lead to inhalational anthrax, which is deadly in humans.

IMPORTANT SAFETY INFORMATION Including BOXED WARNING

WARNING: HYPERSENSITIVITY and ANAPHYLAXIS
Hypersensitivity reactions, including anaphylaxis, have been reported during ANTHIM infusion. ANTHIM should be administered in monitored settings by personnel trained and equipped to manage anaphylaxis. Stop ANTHIM infusion immediately and treat appropriately if hypersensitivity or anaphylaxis occurs.

WARNINGS AND PRECAUTIONS
Hypersensitivity and anaphylaxis have been reported during the IV infusion of ANTHIM. Due to the risk of hypersensitivity and anaphylaxis, ANTHIM should be administered in monitored settings by personnel trained and equipped to manage anaphylaxis. Monitor individuals who receive ANTHIM closely for signs and symptoms of hypersensitivity reactions throughout the infusion and for a period of time after administration. Stop ANTHIM infusion immediately and treat appropriately if hypersensitivity or anaphylaxis occurs. Pre-medication with diphenhydramine is recommended prior to administration of ANTHIM. Diphenhydramine pre-medication does not prevent anaphylaxis and may mask or delay onset of symptoms of hypersensitivity.

ADVERSE REACTIONS
The safety of ANTHIM has been studied only in healthy volunteers. It has not been studied in patients with inhalational anthrax. The most frequently reported adverse reactions were headache, pruritus, infections of the upper respiratory tract, cough, vessel puncture site bruise, infusion site swelling, urticaria, nasal congestion, infusion site pain, and pain in extremity.

USE IN SPECIFIC POPULATIONS
Pediatric Use: There have been no studies of the safety or PK of ANTHIM in the pediatric population.

Entry into a Material Definitive Agreement

On January 31, 2022, Oncotelic Therapeutics, Inc. (the "Company") reported that 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, JAN 31, 2022, View Source [SID1234607613]). The Note and Purchase Agreement are both part of a series of a cumulative funding of upto $1.5 million in three equal monthly instalments. The Note was entered into as continuation of the relationship between the Company and the Holder.

The Purchase Agreements and the Notes contain identical terms to the securities purchase agreements (and promissory notes issued thereunder), to Golden Mountain Partners, LLC on October 25, 2021. The Prior Issuances were previously reported on our Current Report on Form 8-K filed with the Securities and Exchange Commission ("SEC") on October 28, 2021.

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 payroll.

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.

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Year: 2022

Sponsored Research Agreement with University of Pennsylvania

Clarity advances to cohort 2 in the SARTATE™ neuroblastoma trial

First patient dosed in Biocity CD3/EGFR BsAb BC3448 trial

Elusys Therapeutics Finalizes HHS Contract to Deliver ANTHIM®, Its Treatment for Inhalation Anthrax, to the U.S. Department of Health and Human Services

Entry into a Material Definitive Agreement