Pascal Biosciences and S?RSE Technology Optimize Cannabinoid Formulation for Clinical Development of Cancer Treatment

On December 2, 2020 Pascal Biosciences Inc. (TSX.V:PAS) (OTC:BIMUF) ("Pascal" or the "Company") and SōRSE Technology Corporation ("SōRSE") reported that have validated and optimized a formula for oral cannabinoid delivery (Press release, Pascal Biosciences, DEC 2, 2020, View Source [SID1234572398]). Their shared efforts are advancing the cannabinoid PAS-393 towards clinical testing against cancer.

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"This progress is very promising because this step is critical for testing in human volunteers," said Patrick Gray, CEO. "We will next identify a drug product manufacturer to prepare our product for testing in cancer patients treated with checkpoint inhibitors."

This will be the first pharmaceutical use of the novel formulation technology developed by SōRSE and the first clinical trial for Pascal and SōRSE. The collaboration utilizes propriety discoveries by both companies, including Pascal’s intellectual property, which covers the use of cannabinoids in cancer patients treated with checkpoint inhibitors, and SōRSE’s proprietary formulation expertise.

"It’s great to see such rapid progress with the invitro studies using our formulation technology," said SōRSE CEO Howard Lee. "We are on track to enter our first clinical trial with Pascal within a year."

Following characterization of safety and pharmacology in a Phase 1a clinical trial, Pascal and SōRSE may elect to continue clinical development as equal partners in a Phase 1b cancer trial in combination with a checkpoint inhibitor.

Entry into a Material Definitive Agreement

On December 2, 2020, Propanc Biopharma, Inc. (the "Company") reported that it entered into a securities purchase agreement (the "Purchase Agreement") with Geneva Roth Remark Holdings, Inc. ("Geneva"), pursuant to which Geneva purchased a convertible promissory note (the "December 2020 Geneva Note") from the Company in the aggregate principal amount of $78,000, such principal and the interest thereon convertible into shares of the Company’s common stock at the option of Geneva (Filing, 8-K, Propanc, DEC 2, 2020, View Source [SID1234572318]). The transaction contemplated by the Purchase Agreement closed on or about December 4, 2020. The Company intends to use the net proceeds ($75,000) from the December 2020 Geneva Note for general working capital purposes.

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The maturity date of the December 2020 Geneva Note is December 2, 2021 (the "Maturity Date"). The December 2020 Geneva Note shall bear interest at a rate of 8% per annum, which interest may be paid by the Company to Geneva in shares of common stock, but shall not be payable until the December 2020 Geneva Note becomes payable, whether at the Maturity Date or upon acceleration or by prepayment, as described below. Geneva has the option to convert all or any amount of the principal face amount of the December 2020 Geneva Note, starting on May 30, 2021 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 December 2020 Geneva 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 ("Reporting Service") designated by Geneva (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, Geneva shall be restricted from effecting a conversion if such conversion, along with other shares of the Company’s common stock beneficially owned by Geneva and its affiliates, exceeds 4.99% of the outstanding shares of the Company’s common stock.

The December 2020 Geneva Note may be prepaid until 180 days from the issuance date. If the December 2020 Geneva 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 61 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 91 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 121 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 151 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 December 2020 Geneva Note is outstanding, the Company covenants not to, without prior written consent from Geneva, 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 Geneva’s fees and expenses in the aggregate amount of $3,000.

Other than as described above, the December 2020 Geneva 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 December 2020 Geneva 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 December 2020 Geneva 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 Geneva 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 Geneva shares of common stock issuable upon conversion of principal or interest under the December 2020 Geneva Note within three business days of a notice of conversion by Geneva, the Company shall incur a penalty of $1,000, 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 December 2020 Geneva Note will become immediately due and payable and the Company will pay Geneva, in full satisfaction of its obligations in the December 2020 Geneva Note an amount equal to 150% of an amount equal to the then outstanding principal amount of the December 2020 Geneva Note plus any interest accrued upon such event of default or prior events of default (the "Default Amount").

The December 2020 Geneva Note was issued, and any shares to be issued pursuant to any conversion of the December 2020 Geneva 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.

The foregoing description of the Purchase Agreement and the December 2020 Geneva Note does not purport to be complete and is qualified in their entirety by reference to the full text of the Purchase Agreement and the December 2020 Geneva Note, which are filed as Exhibits 10.1 and 4.1, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.

Targovax announces impressive objective responses as well as effects on non-injected lesions in ONCOS-102 trial in anti-PD1 refractory melanoma patients

On December 2, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that the combination of ONCOS-102 and pembrolizumab (Keytruda) has demonstrated 35% best objective response rate (ORR) in anti-PD1 refractory malignant melanoma (Press release, Targovax, DEC 2, 2020, View Source [SID1234572102]).

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In this two-part, open label phase 1 trial the combination of ONCOS-102 and the anti-PD1 checkpoint inhibitor (CPI) pembrolizumab has been tested in patients with advanced, unresectable melanoma who have had disease progression despite treatment with anti-PD1 CPI. This is a particularly challenging patient population, which is resistant to approved immunotherapies and has few treatment alternatives available.

For the trial overall, tumor responses were observed in 7 out of 20 evaluable patients treated with the ONCOS-102 and pembrolizumab combination, translating into an ORR of 35% by RECIST 1.1 criteria.

In addition, there were multiple examples of responses in non-injected lesions, including 2 patients where a non-injected lesion completely disappeared, indicating that ONCOS-102 can induce systemic anti-tumor immunity.

Prof. Jedd Wolchok, Investigator, Memorial Sloan Kettering Cancer Centre, New York said: "Checkpoint inhibitors have had a significant impact on the way we treat melanoma; however, a subset of patients still does not respond or become resistant to treatment. Therefore, there is a high medical need for immune activating agents to overcome resistance to checkpoint blockade. ONCOS-102 is one such agent that can re-sensitize patients to anti-PD1 therapy. Although these are early data, observing objective responses with some occurring in non-injected lesions in this first exploratory phase 1 trial is encouraging, and we will follow with great interest as ONCOS-102 moves forward into later-stage development."

The trial was designed with two parts assessing different dosing regimens. In Part 1, 9 patients were given 3 intra-tumoral ONCOS-102 injections during the first week, followed by systemic treatment with pembrolizumab every third week for up to 24 weeks. As reported in July 2019, preliminary tumor responses were observed in 3 out of 9 patients in at least one CT scan (see link here). 1 patient has since been determined as non-evaluable (trial inclusion criteria not met), and these numbers have now been updated to 3 out of 8 patients with ORR for Part 1.

12 more patients were enrolled in Part 2 of the trial, where an extended dosing regimen of 12 intra-tumoral ONCOS-102 injections was tested; 4 injections during the first two weeks followed by concomitant administration of ONCOS-102 and pembrolizumab from week 3 and every third week for up to 24 weeks. Tumor responses were observed in 4 out of the 12 patients in at least one CT scan. Notably, the patients in Part 2 had markedly more advanced disease than in Part 1, with the majority diagnosed as stage IV metastatic melanoma when entering the trial. Importantly, both regimens had favorable tolerability profiles, with no safety concerns.

These data are very strong compared to other therapies in development for the same indication in combination with anti-PD1 CPI, including TLR-9 agonists and other oncolytic viruses, which have reported ORR of ca. 25-30%. As such, the observed ONCOS-102 response rate and effect in non-injected lesions can be considered class-leading for the treatment of anti-PD1 refractory malignant melanoma.

Oystein Soug, Chief Executive Officer of Targovax, commented: "These impressive efficacy data in anti-PD1 refractory melanoma are the most important clinical results for Targovax to date. The data clearly confirm our hypothesis that ONCOS-102 can benefit cancer patients resistant to checkpoint inhibition by triggering local and systemic immune activation. They also provide evidence of clinical efficacy and establishes ONCOS-102 as one of the most promising combination partners to checkpoint inhibitors. We will now carefully analyze the immunological data and are planning for a confirmatory melanoma trial for the ONCOS-102 and checkpoint inhibitor combination."

The trial (NCT03003676) was conducted at three sites in the US and one site in Norway, with Memorial Sloan Kettering CC being the coordinating site.

Online presentation:

Targovax management will present the data in a live webcast 2 December 2020 at 10:00 CET. You can join the webcast here. It will be possible to ask questions during the presentation. A replay of the webcast will be available in the Investor section under "Presentations" after the event.

Targovax ASA: Invitation to online presentation at 10:00 CET 2 December

On December 2, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that it will present data from its melanoma and mesothelioma trials in an online webcast at 10:00am CET (Press release, Targovax, DEC 2, 2020, View Source [SID1234572102]).

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With reference to the press release issued 1 December 2020 (see link here), Targovax will present data from its phase 1 trial combining ONCOS-102 and the anti-PD1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda) in patients with advanced, unresectable melanoma who have had disease progression despite treatment with anti-PD1 CPI.

Data from the randomized phase 1/2 trial of ONCOS-102 in combination with standard-of-care (SoC) chemotherapy in patients with malignant pleural mesothelioma (MPM), which was released 24 November 2020 (see link here), will also be presented in the webcast.

The webcast starts at 10:00am CET and you can join the webcast here. It will be possible to ask questions during the presentation. A replay of the webcast will be available in the Investor section under "Presentations" after the event.

RenovoRx Continues with Strong Momentum and Reaches Milestone of 100th Patient Enrolled in its Phase III TIGeR-PaC Clinical Trial

On December 2, 2020 RenovoRx, an innovator in targeted cancer therapy, reported it has reached an important milestone with continued momentum and the enrollment of the 100th patient in its phase III TIGeR-PaC clinical trial (Press release, Renovorx, DEC 2, 2020, View Source [SID1234572101]). This trial utilizes the company’s proprietary Trans-Arterial Micro-Perfusion (TAMPTM) technology, a unique method for targeted delivery of chemotherapy to treat solid tumors. The trial is enrolling locally advanced pancreatic cancer patients with inoperable disease in the United States and Europe.

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"During the COVID-19 pandemic, it is vital for patients with cancer symptoms to work with healthcare teams for early diagnosis and treatment planning," said Pashtoon Kasi, MD, MS, oncologist at University of Iowa Health Care and Clinical Assistant Professor of Internal Medicine at Carver College of Medicine. "It is encouraging to see patients continue to enroll in this landmark study when meeting the criteria for the TIGeR-PaC clinical trial, especially despite the situation caused by COVID-19. Hospitals, clinics, and healthcare professionals are working extremely hard to provide safe environments for patients to initiate and keep going with treatment in a multi-disciplinary fashion."

Dr. Kasi added, "We have seen remarkable benefits for pancreatic cancer patients in previous studies with this promising therapy including better quality of life and extension of life. For patients with unresectable pancreas cancer who have limited options, it is of value to be able to provide therapy under this important clinical trial."

The TIGeR-PaC trial’s goal is to determine whether the TAMP procedure can reduce the chance of cancer spreading and extend survival while improving quality of life for pancreatic cancer patients. The study, which currently has approximately 30 active clinical sites, is ultimately expected to involve 200 participants in the US and Europe. To learn more, visit View Source

"We are pleased that we have reached this 100th patient enrollment milestone, especially during this challenging time. The progress we continue to make with this clinical trial is our primary focus as we work toward our goal of improving outcomes for cancer patients," said Shaun Bagai, Chief Executive Officer at RenovoRx. "We appreciate our physician investigators, study coordinators, nurses, clinical teams and, most importantly, our patients for their commitment and participation in this important trial."

RenovoRx recently won the Fierce Innovation Awards – Life Sciences Edition 2020 award for its TAMP technology. The peer reviewed awards program from the publisher of Fierce Biotech and Fierce Pharma honors companies demonstrating innovative solutions, technologies, and services that could make the greatest impact for biotech and pharma companies.