FDA Grants Fast Track Status to Novel Gene Therapy Plus Pembrolizumab for Late-Stage NSCLC

On January 4, 2022 Genprex reported that FDA has granted a fast track designation to a combination comprised of the immunogene therapy quaratusugene ozeplasmia (REQORSA) and pembrolizumab (Keytruda) for use in patients with histologically confirmed, unresectable, stage III or IV non–small cell lung cancer (NSCLC) who experienced disease progression following treatment with pembrolizumab (Press release, Genprex, JAN 4, 2022, View Source [SID1234607477]).1

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The product utilizes Genprex, Inc.’s proprietary ONCOPREX Nanoparticle Delivery System, which is believed to be the first systemic gene delivery platform leveraged for cancer in humans, according to the clinical-stage gene therapy company.2

Quaratusugene ozeplasmia is comprised of the tumor suppressor gene, TUSC2, which is encapsulated in a nanoparticle composed from lipid molecules with a positive electrical charge. The product is intravenously administered, and was designed to target cancer cells, which are known to generally have a negative charge. Once the product is taken into the cancer cell, the gene is expressed into a protein that can restore select defective functions that arise in the cancer cell.

The gene therapy has a multimodal mechanism of action in that it can disrupt cell-signaling pathways that are responsible for the replication and proliferation of cancer cells; it can also re-establish pathways for apoptosis and modulate the immune system so that it responds against cancer cells.

Additionally, the pan-kinase inhibitor simultaneously inhibits the EGFR and AKT pathways both in vitro and in vivo. When a cancer cell takes up the TUSC2-containing nanoparticle, it is reprogrammed to die. It is known that resistance to existing targeted agents and checkpoint inhibitors can develop when alternate bypass pathways are activated. The multimodality activity of the gene therapy allows it to block emerging bypass pathways and reduce the probability of drug resistance.

"We are thrilled to receive a second fast track designation from the FDA for REQORSA in patients with late-stage NSCLC, this time in combination with the checkpoint inhibitor pembrolizumab," Rodney Varner, president and chief executive officer at Genprex, stated in a press release. "This fast track designation is an important step in our efforts to accelerate clinical development of REQORSA and another validation of the potential of REQORSA to treat the unmet medical need of patients with late-stage NSCLC."

In the first quarter of 2022, the company expects to launch the open-label, multicenter, phase 1/2 Acclaim-2 trial (NCT05062980), which will evaluate the safety and efficacy of the gene therapy in combination with pembrolizumab in patients with previously treated NSCLC.3

Entry into a Material Definitive Agreement

On January 4, 2022, Propanc Biopharma, Inc. (the "Company") reported that it entered into a securities purchase agreement (the "Purchase Agreement") with Sixth Street Lending, LLC ("Sixth Street"), pursuant to which Sixth Street purchased a convertible promissory note (the "Note") from the Company in the aggregate principal amount of $63,750, such principal and the interest thereon convertible into shares of the Company’s common stock at the option of Sixth Street (Filing, 8-K, Propanc, JAN 4, 2022, View Source [SID1234598499]). The transaction contemplated by the Purchase Agreement closed on January 6, 2022. The Company intends to use the net proceeds ($60,000) from the Note for general working capital purposes.

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The maturity date of the Note is October 21, 2022 (the "Maturity Date"). The Note shall bear interest at a rate of 8% per annum, which interest may be paid by the Company to Sixth Street in shares of common stock, but shall not be payable until the Note becomes payable, whether at the Maturity Date or upon acceleration or by prepayment, as described below. Sixth Street has the option to convert all or any amount of the principal face amount of the Note, starting on July 3, 2022, and ending on the later of the Maturity Date and the date of payment of the Default Amount (as defined below) is paid if an event of default occurs, for shares of the Company’s common stock at the then-applicable conversion price. The conversion price for the Note shall be equal to the Variable Conversion Price (as defined herein) (subject to equitable adjustments for stock splits, stock dividends or rights offerings by the Company relating to the Company’s securities or the securities of any subsidiary of the Company, combinations, recapitalization, reclassifications, extraordinary distributions and similar events). The "Variable Conversion Price" shall mean 65% multiplied by the Market Price (as defined herein) (representing a discount rate of 35%). "Market Price" means the average of the lowest three (3) Trading Prices (as defined below) for the Common Stock during the ten (10) Trading Day period ending on the latest complete Trading Day prior to the Conversion Date. "Trading Price" means, for any security as of any date, the closing bid price on the OTCQB, OTCQX, Pink Sheets electronic quotation system or applicable trading market (the "OTC") as reported by a reliable reporting service designated by Sixth Street (i.e. Bloomberg) or, if the OTC is not the principal trading market for such security, the closing bid price of such security on the principal securities exchange or trading market where such security is listed or traded or, if no closing bid price of such security is available in any of the foregoing manners, the average of the closing bid prices of any market makers for such security that are listed in the "pink sheets". Notwithstanding the foregoing, Sixth Street shall be restricted from effecting a conversion if such conversion, along with other shares of the Company’s common stock beneficially owned by Sixth Street and its affiliates, exceeds 4.99% of the outstanding shares of the Company’s common stock.

The Note may be prepaid until 180 days from the issuance date. If the Note is prepaid within 60 days of the issuance date, then the prepayment premium shall be 110% of the face amount plus any accrued interest, if prepaid after 60 days from the issuance date, but less than 91 days from the issuance date, then the prepayment premium shall be 115% of the face amount plus any accrued interest, if prepaid after 90 days from the issuance date, but less than 121 days from the issuance date, then the prepayment premium shall be 120% of the face amount plus any accrued interest, if prepaid after 120 days from the issuance date, but less than 151 days from the issuance date, then the prepayment premium shall be 125% of the face amount plus any accrued interest, and if prepaid after 150 days from the issuance date, but less than 181 days from the issuance date, then the prepayment premium shall be 129% of the face amount plus any accrued interest. So long as the Note is outstanding, the Company covenants not to, without prior written consent from Sixth Street, 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 such term is defined in Rule 144. Pursuant to the terms of the Purchase Agreement, the Company paid Sixth Street’s fees and expenses in the aggregate amount of $3,750.

Other than as described above, the Note contains certain events of default, including failure to timely issue shares upon receipt of a notice of conversion, as well as certain customary events of default, 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 Note. Additional events of default shall include, among others: (i) failure to reserve at least five times the number of shares issuable upon full conversion of the Note; (ii) bankruptcy, insolvency, reorganization or liquidation proceedings or other proceedings, voluntary or involuntary, for relief under any bankruptcy law or any law for the relief of debtors shall be instituted by or against the Company or any subsidiary of the Company; provided, that in the event such event is triggered without the Company’s consent, the Company shall have sixty (60) days after such event is triggered to discharge such event, (iii) the Company’s 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, the Nasdaq National Market, the Nasdaq Small Cap Market, the New York Stock Exchange, or the American Stock Exchange, (iv) The restatement of any financial statements filed by the Company with the SEC at any time after 180 days after the issuance date for any date or period until this note is no longer outstanding, if the result of such restatement would, by comparison to the un-restated financial statement, have reasonably constituted a material adverse effect on the rights of Sixth Street with respect to this note or the Purchase Agreement, and (v) the Company’s failure to comply with its reporting requirements of the Securities and Exchange Act of 1934 (the "Exchange Act"), and/or the Company ceases to be subject to the reporting requirements of the Exchange Act.

In the event that the Company fails to deliver to Sixth Street shares of common stock issuable upon conversion of principal or interest under the Note within three business days of a notice of conversion by Sixth Street, the Company shall incur a penalty of $1,000 per day, provided, however, that such fee shall not be due if the failure to deliver the shares is a result of a third party such as the transfer agent.

Upon the occurrence and during the continuation of certain events of default, the Note will become immediately due and payable and the Company will pay Sixth Street, in full satisfaction of its obligations in the Note an amount equal to 150% or 200% of an amount equal to the then outstanding principal amount of the Note, dependent on the nature of the default, plus any interest accrued upon such event of default or prior events of default.

The Note was issued, and any shares to be issued pursuant to any conversion of the Note shall be issued, in a private placement in reliance upon an exemption from registration provided by Section 4(a)(2) of the Securities Act and/or Regulation D promulgated thereunder.

CUMBERLAND PHARMACEUTICALS ACQUIRES SANCUSO® FROM KYOWA KIRIN NORTH AMERICA

On January 4, 2022 Cumberland Pharmaceuticals Inc. (NASDAQ: CPIX), a specialty pharmaceutical company, reported that it has entered into and closed on a definitive agreement to acquire the FDA-approved oncology-supportive care medicine SANCUSO (granisetron transdermal patch), from Kyowa Kirin, Inc. the U.S. affiliate of Japan-based Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company focused on discovering and delivering novel medicines (Press release, Cumberland Pharmaceuticals, JAN 4, 2022, View Source [SID1234598338]).

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SANCUSO is the first and only FDA-approved prescription patch for the prevention of nausea and vomiting in patients receiving certain types of chemotherapy treatment. The active drug in SANCUSO, granisetron, slowly dissolves in the thin layer of adhesive that sticks to the patient’s skin and is released into their bloodstream over several days, working continuously to prevent chemotherapy-induced nausea and vomiting (CINV). It is applied 24 to 48 hours before receiving chemotherapy and can prevent CINV for up to five consecutive days. Alternative oral treatments must be taken several times (day and night) to deliver the same therapeutic doses.

"In 2020 there were nearly two million new cases of cancer in the U.S. and each year over half a million Americans undergo chemotherapy, with many suffering from the side effects of their treatment. With SANCUSO, patients are given a simple, easy-to-apply preventative solution that doesn’t require swallowing any pills – which can be difficult for patients experiencing nausea," said A.J. Kazimi, chief executive officer at Cumberland Pharmaceuticals. "We are honored to take responsibility for the brand and introduce it through our commercial organization, ensuring that it is delivered to the patients who need it."

Under the terms of the agreement, Cumberland will acquire U.S. rights to SANCUSO and will assume full commercial responsibility for the product – including its marketing, promotion, distribution, manufacturing and medical support activities. Net sales of the brand in the U.S. were over $14 million in 2020. The financial terms of the acquisition include a $13.5 million payment to Kyowa Kirin upon closing, up to $3.5 million in milestones and tiered royalties of up to 10% on U.S. net product sales. Kyowa Kirin will retain international rights, continuing to deliver the product to address oncology patients’ needs throughout the rest of the world.

"Since its launch in 2008, we have established SANCUSO as an important supportive therapeutic solution for oncology patients across the country," said Gary Zieziula, president of Kyowa Kirin North America. "We believe that Cumberland is well positioned to optimize the value of the brand and ensure that this unique product continues to deliver important therapeutic benefits to oncology patients."

Akari Therapeutics to Present at H.C. Wainwright BioConnect Virtual Conference

On January 4, 2022 Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement (C5) and/or leukotriene (LTB4) systems are implicated, reported that Clive Richardson, Chief Executive Officer, will present a Company overview at the H.C. Wainwright BioConnect Conference being held virtually January 10-13, 2022 (Press release, Akari Therapeutics, JAN 4, 2022, View Source [SID1234598319]).

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The pre-recorded presentation will be available on-demand beginning January 10, 2022 at 7:00 a.m. ET by visiting ‘Events’ in the Investor Relations section of the Company’s website at www.akaritx.com. A webcast replay will be accessible for 90 days following the event.

Sangamo Therapeutics Announces Participation at H.C. Wainwright BIOCONNECT Virtual Conference

On January 4, 2022 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported that management will provide a corporate presentation at the H.C. Wainwright BIOCONNECT Virtual Conference on Monday, January 10th at 7:00 a.m. Eastern Time (Press release, Sangamo Therapeutics, JAN 4, 2022, View Source [SID1234598251]).

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The virtual session may be accessed on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. The presentation will also be available on the Sangamo Therapeutics website after the event.