On January 4, 2022- Alphamab Oncology and CSPC Pharmaceutical Group Co., Ltd. jointly reported that the IND application for the pivotal clinical trial (KN026-CSP-001) of the anti-HER2 bispecific antibody KN026 combined with chemotherapy was approved by the Center for Drug Evaluation (CDE) of NMPA (Press release, Alphamab, JAN 4, 2022, View Source [SID1234611313]).

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KN026-CSP-001 is a randomized, multi-center, phase II/III clinical study to evaluate the efficacy and safety of KN026 combined with chemotherapy in patients with HER2-positive gastric cancer (including gastroesophageal junction cancer) who have failed first-line treatment, with Professor Jianming Xu from the Chinese People’s Liberation Army General Hospital as principal investigator.

GC/GEJ is one of the common malignant tumors and there are more than 1 million new cases each year in the world. The incidence of gastric cancer is high in China, with about 410,000 new cases and 294,000 deaths each year, accounting for more than 40% of both new and death cases of GC/GEJ worldwide. Gastric cancer in China is characterized by low diagnosis rate of early gastric cancer, high proportion of metastatic stage (>80%) and low 5-year survival rate (about 35.1%), which seriously threatens the life and health of people. HER2 is overexpressed in many tumors, including about 15-20% in gastric cancer. HER2 overexpression is related to tumor aggressiveness and poor prognosis. With the development of targeted therapies, HER2-positive advanced gastric cancer patients have achieved better efficacy compared to traditional chemotherapy when treated with a combination of targeted drugs. However, for patients with HER2-positive gastric cancer who have progressed or recurred after first-line treatment, there is no effective drug approved in China, and there is a huge unmet clinical need.

KN026 is a HER2 bispecific antibody developed by Alphamab Oncology. Data from the Phase II clinical study of KN026, published at ASCO (Free ASCO Whitepaper) in 2021, demonstrated favorable safety and promising efficacy in Chinese HER2 overexpressing GC/GEJ patients, pretreated either with or without anti HER2 treatments. In patients with high expression, the ORR was 55.6% and the DCR was 72.2%, and the 9-month PFS rate was 60.4%. Among patients receiving prior-HER2 treatment, the ORR was 44.4%, and the DCR was 66.7%. The approval of the clinical trial application is a touchstone for the cooperation between Alphamab Oncology and CSPC to accelerate the clinical development and commercialization of KN026 in mainland China. We hope to see more positive data from the study, and bring hope to patients with advanced gastric cancer who are in urgent need of new treatment options.

About KN026
KN026 is an anti-HER2 bispecific antibody developed by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology called CRIB (Charge Repulsion Induced Bispecific). KN026 can bind two non-overlapping epitopes of HER2 simultaneously, leading to a dual HER2 signal blockade. KN026 has demonstrated potentially equivalent efficacy compared with Trastuzumab and Pertuzumab in combination, and was superior to either single agent, such as increased binding affinity, as well as better tumor inhibition in HER2-positive tumor cell lines. Additionally, KN026 has also shown inhibitory effect on tumor cells with medium or low HER2 expression or Trastuzumab-resistant cell lines.

KN026 received IND approval from the National Medical Products Administration (NMPA) of China and U.S. Food and Drug Administration (FDA) in 2018. Currently, it is in multiple phase I/II clinical trials in China and phase I clinical trial in the United States. The results of Phase I clinical trials show KN026 has good safety, tolerance and potentially superior anti-tumor activity in HER2-positive breast cancer patients who progressed after multiple lines of anti-HER2 treatment.

In August 2021, the company entered an agreement with JMT-Bio, a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (stock code: 1093.HK), for the development and commercialization of KN026 in Mainland China. According to the terms of the agreement, JMT-Bio will obtain the exclusive license rights of KN026 for the development and commercialization in the indications of breast cancer and gastric or gastroesophageal junction cancers (GC/GEJ) in Mainland China (excluding Hong Kong, Macau and Taiwan).

On January 4, 2022 Lyell Immunopharma, Inc., (NASDAQ: LYEL), a T-cell reprogramming company dedicated to the mastery of T cells to cure patients with solid tumors, reported that members of its senior management team will participate in the 40th Annual J.P. Morgan Healthcare Conference on Tuesday, January 11, at 3:00 PM ET (Press release, Lyell Immunopharma, JAN 4, 2022, View Source [SID1234609997]).

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During the conference, the Company will highlight its:

Pipeline of CAR, TIL and TCR product candidates across multiple solid tumor indications of high unmet medical need including LYL797, a CAR T-cell therapy for solid tumors. Lyell expects to begin screening patients for its Phase 1 clinical trial of LYL797 by the end of the first quarter, with initial data presentation expected in 2023.
Novel platform technologies – Gen-R and Epi-R – designed to enable T cells to resist exhaustion, self-renew and proliferate to outlast and eradicate solid tumors.
LyFE Manufacturing Center, built to provide greater control over Lyell’s supply chain and maximize efficiencies in cell product production time, cost and quality. LyFE is qualified in compliance with the U.S. Food and Drug Administration’s Current Good Manufacturing Practices (cGMP) and has completed successful engineering runs at scale.
A live webcast of the presentation can be accessed through the Investors section of the Company’s website at www.lyell.com. Following the live presentation, a replay of the webcast will be available on the Company’s website for 30 days following the presentation date.

On January 4, 2022 Genprex reported that The US Food and Drug Administration (FDA) has granted fast track designation (FTD) to it’s lead drug candidate, Reqorsa Immunogene Therapy, plus Keytruda to treat histologically confirmed unresectable stage III or IV non-small cell lung cancer (NSCLC) (Press release, Genprex, JAN 4, 2022, View Source [SID1234607494]).

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The combination treatment is intended for use in NSCLC patients whose disease advanced on receiving Keytruda treatment.

Keytruda is a checkpoint inhibitor of Merck & Co’s (MSD).

Genprex anticipates commencing a multicentre, open-label Phase I/II Acclaim-2 clinical trial of Reqorsa plus Keytruda to treat NSCLC in the first quarter of this year.

This is the second FTD granted by the FDA for Reqorsa.

The first status was granted for Reqorsa plus AstraZeneca’s Tagrisso to treat histologically confirmed unresectable stage III or IV NSCLC patients with EGFR mutations that advanced on receiving Tagrisso.

According to the preclinical data, Reqorsa plus Keytruda demonstrated to be efficient over treatment with Keytruda alone to boost survival in mice with a humanised immune system having metastatic lung tumours.

The drug’s multiple impacts on the immune system such as a rise in natural killer cells and a reduction in PD-L1 expression on cancer cells were observed in these mice studies.

This is believed to add to the synergy of Reqorsa seen with Keytruda.

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

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.