On August 19, 2021, Palisade Bio, Inc. (the "Company") and Yuma Regional Medical Center (the "Investor") reported that it entered into a Securities Purchase Agreement (the "Purchase Agreement") pursuant to which the Investor purchased 1,509,896 shares (the "Shares") of the Company’s common stock, par value $0.01 per share (the "Common Stock") and a warrant to purchase up to 377,474 shares of Common Stock (the "Warrant") for a total purchase price of $5,209,141.20 (Filing, 8-K, Seneca Biopharma, AUG 19, 2021, View Source [SID1234586848]). The Shares were sold at a purchase price of $3.45 per share. The Warrant has an exercise price of $3.45 per share, subject to certain adjustments, and is exercisable for five years.

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Pursuant to the Purchase Agreement, the Company has agreed to file one or more registration statements with the Securities and Exchange Commission (the "SEC") registering the resale of the Shares and the shares of Common Stock issuable upon exercise of the Warrant by the Investor, to have all such registration statements declared effective within the timeframes set forth in the Purchase Agreement, and to keep such registration statements effective for up to five years. The Company will bear all expenses of the registration, excluding fees of legal counsel for Investor.

The Purchase Agreement contains customary representations and warranties of the Company and the Investor. The representations, warranties and covenants contained in the Purchase Agreement were made only for purposes of such Purchase Agreement and are made as of specific dates; are solely for the benefit of the parties (except as specifically set forth therein); may be subject to qualifications and limitations agreed upon by the parties in connection with negotiating the terms of the Purchase Agreement, including being qualified by confidential disclosures made for the purpose of allocating contractual risk between the parties, instead of establishing matters as facts; and may be subject to standards of materiality and knowledge applicable to the contracting parties that differ from those applicable to the investors generally. Investors should not rely on the representations, warranties and covenants or any description thereof as characterizations of the actual state of facts or condition of the Company.

The Investor was a stockholder of the Company prior to the investment described above. Robert J. Trenschel, D.O., is a member of the Company’s board of directors and is the president and chief executive officer of the Investor. Dr. Trenschel does not have any pecuniary interest in the Company’s securities that are owned by the Investor.

On August 19, 2021 Allarity Therapeutics A/S ("Allarity" or the "Company") reported a new publication date for the Company’s Q2 2021 Interim Report, which is now being made public on August 23, 2021 (previously: August 31, 2021) (Press release, Allarity Therapeutics, AUG 19, 2021, View Source [SID1234586789]).

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The reason for the change of publication date is to accelerate the Company’s preparations for the transformation and recapitalization as announced on May 21, 2021 as the Company advances towards migration to listing on the U.S. Nasdaq stock market (New York, N.Y.).

On August 19, 2021 Gilead Sciences reported that Researchers with the Georgia Institute of Technology recently published work in Nature Biomedical Engineering that describes several new approaches to improving CAR-T, particularly for solid tumors (Press release, Gilead Sciences, AUG 19, 2021, View Source [SID1234586782]).

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CAR-T therapy, such as Gilead Sciences’ Yescarta (axicabtagene ciloleucel) for non-Hodgkin lymphoma, acute lymphoblastic leukemia, mantle cell lymphoma and other indications, and Novartis’ Kymriah (tisagenlecleucel), approved for acute lymphoblastic leukemia, chronic lymphoid leukemia, diffuse large B-cell lymphoma, as well as others, are very effective for hematologic cancers. However, getting CAR-T to work in solid tumors has been a tougher nut to crack.

In CAR-T (chimeric antigen receptor T-cell) therapy, T-cells are isolated from a cancer patient, engineered in the laboratory by adding a gene for a chimeric antigen receptor (CAR), grown, then infused back into the patient. There, they become a sort of living therapy highly tuned to attack the patient’s cancer.

"These therapies have proven to be remarkably effective for patients with liquid tumors — so, tumors that are circulating in the blood, such as leukemia," Gave Kwong, associate professor in the Wallace H. Coulter Department of biomedical engineering at Georgia Tech and Emory, and senior study investigator told Genetic Engineering & Biotechnology News. "Unfortunately, for solid tumors — sarcomas, carcinomas — they don’t work well. There are many different reasons why. One huge problem is that the CAR T-cells are immunosuppressed by the tumor microenvironment."

Kwong’s team is working to change the microenvironment to improve CAR-T in these cancers. One approach is to create an on-off switch that is sensitive to heat.

Earlier work conducted by his research group precisely targets tumors with a local deposit of heat, which activates the CAR-T cells inside the tumor. To create heat, they used laser pulses from outside the body. Gold nanorods that are delivered to the tumor convert the light waves into localized heat, increasing the temperature to 40 to 42 degrees C, which activates the switch but doesn’t harm healthy tissues or the T-cells.

In addition to genetically engineering the CAR-T cells to respond to that switch, they have also redesigned them to manufactures immune stimulatory molecules. These cytokines and bispecific T-cell engagers are controlled carefully.

Kwong said, "These cancer-fighting proteins are really good at stimulating CAR T-cells, but they are too toxic to be used outside of tumors. They are too toxic to be delivered systemically. But with our approach, we can localize these proteins safely. We get all the benefits without the drawbacks."

The study was conducted on mice. The research led to a 60-fold-higher expression of a reporter transgene without affecting the CAR-T cells’ proliferation, migration, and cytotoxicity. The system cured cancer in the mice, shrinking tumors and preventing relapse.

The researchers say that when they test it in humans, instead of the laser, they will use focused ultrasound, which is noninvasive while targeting any location in the body. Lasers don’t penetrate far enough into the body to be a practical approach in humans.

"So," Kwong said, "if you have a deep-seated malignant tumor, that would be a problem. We want to eliminate problems."

On August 19, 2021 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs, reported the pricing of an underwritten public offering of 35,294,117 shares of common stock or common stock equivalents (which includes pre-funded warrants to purchase shares of common stock in lieu of shares of common stock) and investor warrants to purchase up to an aggregate of 35,294,117 shares of common stock (Press release, Sonnet BioTherapeutics, AUG 19, 2021, View Source [SID1234586778]). Each share of common stock (or pre-funded warrant in lieu thereof) is being sold together with one investor warrant to purchase one share of common stock at a combined offering price of $0.85, for total gross proceeds of approximately $30.0 million, before underwriting discounts and commissions and offering expenses payable by Sonnet. The investor warrants have an exercise price of $0.85 per share. The offering is expected to close on or about August 24, 2021, subject to the satisfaction or waiver of customary closing conditions.

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BTIG is acting as the sole book-running manager in connection with the offering and Chardan is acting as lead manager.

The Company has also granted the underwriters a 30-day option to purchase up to 5,294,117 additional shares of its common stock and/or investor warrants to purchase up to 5,294,117 additional shares of its common stock, in any combination thereof, at the public offering price, less underwriting discounts and commissions, to cover over-allotments, if any.

Sonnet anticipates using the net proceeds from the offering for research and development, including clinical trials, working capital and general corporate purposes.

The securities will be offered pursuant to a registration statement on Form S-1, as amended (File No. 333-258092), which was declared effective by the Securities and Exchange Commission (the "SEC") on August 19, 2020. The offering is being made solely by means of a prospectus. A preliminary prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus and, when available, copies of the final prospectus relating to this offering can be obtained at the SEC’s website at www.sec.gov or from BTIG, LLC, Attention: Equity Capital Markets, 65 East 55th Street, New York, NY 10022, by calling (212) 593-7555 or by e-mail at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor will there be any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction.

On August 19, 2021 NuCana plc (NASDAQ: NCNA) reported its financial results for the second quarter ended June 30, 2021 and provided an update on its broad clinical program with its transformative ProTide therapeutics (Press release, Nucana BioPharmaceuticals, AUG 19, 2021, View Source [SID1234586776]).

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As of June 30, 2021, NuCana had cash and cash equivalents of £73.4 million compared to £78.6 million at March 31, 2021 and £87.4 million as of December 31, 2020. NuCana continues to advance its various clinical programs and reported a net loss of £9.1 million for the quarter ended June 30, 2021, as compared to a net loss of £6.1 million for the quarter ended June 30, 2020. Basic and diluted loss per share was £0.17 for the quarter ended June 30, 2021, as compared to £0.19 per share for quarter ended June 30, 2020.

"It has been a productive first half of 2021 with our release of important non-clinical and clinical data announcements. These include data from the NuTide:302 Phase Ib study of NUC-3373 in patients with advanced colorectal cancer as well as from the NuTide:701 Phase I study of NUC-7738 in patients with advanced solid tumors," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "These data presentations, made at several medical conferences, continue to support the favorable clinical profile we have observed to date and the broad potential of our ProTide technology."

Mr. Griffith continued: "As we look ahead to the second half of the year, we anticipate presenting additional clinical data from NUC-3373 and NUC-7738. Despite the COVID-19 pandemic, we remain on track to recruit sufficient patients in 2021 in the ongoing NuTide:121 Phase III clinical study of Acelarin combined with cisplatin as a first-line treatment for patients with advanced biliary tract cancer to enable the first interim analysis in 2022. We are hopeful that this could enable us to submit an NDA in the United States under the FDA’s accelerated approval program. We are also on track with other key milestones, including the initiation this year of a Phase III study of NUC-3373 in combination with other agents for patients with colorectal cancer."

Mr. Griffith also noted that NuCana has established preliminary objectives for the first half of 2022: "We are looking forward to 2022, which will be an important and active year for NuCana. With Acelarin, we anticipate announcing whether the NuTide:121 study has achieved the overall response rate objective at the first interim analysis in the first half of 2022. Additionally, based on the encouraging data seen to date with NUC-3373 and 5-FU’s broad usage in oncology, we anticipate initiating in 2022 a Phase Ib basket study of NUC-3373 in combination with other agents in a variety of solid tumors to identify further indications to target. We also expect to announce in 2022 data from the Phase II study of NUC-7738, which is anticipated to start later in 2021."

Mr. Griffith concluded: "Lastly, it is my pleasure to welcome Dr. Jeffrey Bloss to NuCana as our new Chief Medical Officer. Jeff brings more than two decades of relevant oncology experience leading clinical development and medical affairs at a number of companies. Over his career, he has been a key member of the teams responsible for the development, approval and commercialization of over ten successful oncology drugs including Gemzar, Tarceva, Sorafenib, Tykerb and Xtandi. His experience and contributions will be invaluable to NuCana as we continue to advance our pipeline of novel ProTides through the clinic and towards commercialization."

Anticipated Milestones: H2 2021 & H1 2022

•Acelarin (a ProTide transformation of gemcitabine)

ºIn 2021, NuCana expects to reach enrollment of at least 418 evaluable patients to enable the first interim analysis in 2022 of the Phase III study of Acelarin combined with cisplatin as a first-line treatment for patients with advanced biliary tract cancer; and
ºIn the first half of 2022, NuCana expects to announce whether the overall response rate objective for the first interim data from this Phase III study has been met, which may enable an NDA submission in the United States under the FDA’s accelerated approval program.

•NUC-3373 (a ProTide transformation of 5-FU)

In 2021, NuCana expects to:

ºReport data from the Phase Ib study (NuTide:302) of NUC-3373 in combination with other agents with which 5-FU is typically combined, such as leucovorin, oxaliplatin and irinotecan in patients with advanced colorectal cancer;
ºInitate and report data from the Phase Ib expansion / Phase II study of NUC-3373 in combination with other agents for patients with colorectal cancer;
ºInitiate a Phase III study of NUC-3373 in combination with other agents for patients with colorectal cancer; and
ºReport data from the Phase I study (NuTide:301) of NUC-3373 in patients with advanced solid tumors.
In the first half of 2022, NuCana expects to:
ºInitiate a Phase Ib basket study of NUC-3373 in combination with other agents in a variety of solid tumors; and
ºExpand the Phase Ib / Phase II study to include second-line colorectal cancer patients, as well as evaluate NUC-3373 in combination with monoclonal antibodies such as bevacizumab (Avastin).

•NUC-7738 (a ProTide transformation of 3’-deoxyadenosine)

In 2021, NuCana expects to:

ºReport data from the Phase I study (NuTide:701) of NUC-7738 in patients with advanced solid tumors; and
ºInitiate a Phase II study of NUC-7738 in patients with solid tumors.

In the first half of 2022, NuCana expects to:

ºAnnounce data from the Phase II study of NUC-7738 in patients with solid tumors.