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InteRNA Technologies Publishes Preclinical Data from Investigational microRNA INT-1B3 Program in Molecular Therapy – Nucleic Acids and Oncotarget

On March 24, 2021 InteRNA Technologies, a clinical-stage biotech company developing microRNA (miRNA)-based therapeutics with a focus on cancer, reported that preclinical data investigating the Company’s lead candidate, INT-1B3, have been published in the peer-reviewed journals Molecular Therapy – Nucleic Acids and Oncotarget (Press release, InteRNA Technologies, MAR 24, 2021, View Source [SID1234577094]). INT-1B3 is a mimic of the tumor suppressor miRNA-193a-3p and has the potential to address multiple hallmarks of cancer at the same time. The published results include data from tumor cell lines and experimental tumor models and support the high therapeutic potential of INT-1B3 in solid tumor indications.

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"Publications of our preclinical data with INT-1B3 in two highly-ranked, peer-reviewed journals represent a major milestone for our research and development team, and recognition of the innovative scientific research conducted at InteRNA in the last few years," said Dr. Michel Janicot, Chief Development Officer of InteRNA Technologies. "Documenting the molecular mechanism of action of our miR-193a-3p mimic and consequent downstream biology in cancer cells strongly supports INT-1B3 as novel promising candidate for therapeutic intervention in oncology."

In the publication in Molecular Therapy – Nucleic Acids, results of extended RNA-sequencing and transcriptome-wide analysis after transfection of the miR-193a-3p mimic (1B3) in human tumor cell lines were presented, revealing insights into the underlying molecular pathways of 1B3’s tumor suppressor functions. Differentially expressed genes mapped by Ingenuity Pathway Analysis strongly indicated upregulation of the tumor suppressive PTEN pathway as well as downregulation of many oncogenic growth factor signaling pathways. Furthermore, the analysis pointed to an extensive link of 1B3 with cancer, based on predicted negative effects on tumor cell survival, proliferation and migration as well as induction of cell death in tumor cells. These data strongly suggest that 1B3 is a potent tumor suppressor agent which targets various key hallmark pathways across cancer types.

In the publication in Oncotarget, preclinical data from different tumor cell-based assays demonstrated multi-modal effects of 1B3 on cancer cells. 1B3 was shown to efficiently reduce target gene expression in tumor cells, leading to diminished cell proliferation and survival, induction of cell cycle arrest and apoptosis, increased cell senescence, DNA damage and inhibition of cell migration. In addition, the novel lipid nanoparticle (LNP)-based formulation of 1B3, INT-1B3, demonstrated pronounced anti-tumor activity as a single agent upon systemic administration in tumor-bearing mice at well-tolerated doses.

These preclinical results contributed to the decision by InteRNA to initiate a first-in-human clinical study with INT-1B3 in patients with advanced solid tumors. The first patient in the study was dosed in February 2021. The trial is conducted in clinical study centers in the Netherlands and Belgium and topline results from the dose escalation part of the study are expected by the end of 2021.

About INT-1B3

INT-1B3’s unique mechanism of action addresses multiple hallmarks of cancer simultaneously. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components across the PTEN tumor suppressor pathway and the oncogenic PI3K/Akt and Ras/MAPK pathways resulting in inhibition of proliferation and migration and induction of cell cycle arrest and apoptosis. The triggering of the immunogenic tumor cell death (ICD) process as well as downregulation of the adenosine-A2A receptor pathway through inhibition of CD39/CD73 leads to a decrease in immunosuppressive FoxP3/Lag3 regulatory T cells and monocytic myeloid-derived suppressor cells (mMDSCs), and maturation of dendritic cells. As a result, the immune system is activated, and long-term immunity is triggered by recruitment of CD8+ effector T cells leading to decreased metastasis development and improved animal survival compared to anti-PD1 treatment.

Actinium Announces Initiation of Patient Enrollment in Iomab-ACT Trial for Targeted Conditioning Prior to CD19 CAR T-Cell Therapy

On March 24, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that its collaborator, Memorial Sloan Kettering Cancer Center ("MSK"), has commenced patient enrollment in the Phase 1 study evaluating Iomab-ACT for targeted conditioning prior to treatment with MSK’s CD19 targeted CAR T-cell 19-28z (Press release, Actinium Pharmaceuticals, MAR 24, 2021, View Source [SID1234577093]). Iomab-ACT is a low dose version of Actinium’s Phase 3 drug candidate Iomab-B, a CD45 targeting antibody radiation conjugate ("ARC"). Actinium and MSK were jointly awarded National Institutes of Health Small Business Technology Transfer grant funding for this first ever trial to evaluate ARC-based targeted conditioning prior to CAR-T therapy. The scientific rationale for this trial builds on preclinical data published in 2020 and is further supported by clinical observations from the SIERRA trial to justify combining MSK’s 19-28z CAR T-cell therapy with Iomab-ACT. Manufacturing of patient CAR T-cells has commenced and patient conditioning with Iomab-ACT followed by 19-28z CAR T-cell infusion is expected early in the second quarter of 2021, with proof-of-concept data expected in the second half of 2021.

Results of a Phase 2 trial in 53 patients with relapsed and refractory B-cell acute lymphoblastic leukemia with MSK’s 19-28z CAR-T published in the New England Journal of Medicine reported complete remissions in 83% (44/53) of patients, median event-free survival (EFS) of 6.1 months and median overall survival (OS) was 12.9 months at a median follow up period of 29 months (range 1 – 65 months). There was a 26% (14/53) rate of Grade 3 of greater cytokine release syndrome (CRS), with 1 patient death as a result, and 42% of patients experienced Grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS).

Dr. Dale Ludwig, Actinium’s Chief Scientific and Technology Officer, said "MSK’s 19-28z CAR T-cell therapy has produced high response rates in patients with relapsed or refractory B-ALL who have previously undergone several lines of standard therapy. However, toxicities such as cytokine release syndrome and neurologic toxicity, as well as durability of response, remain a significant challenge. The ARC technology Iomab-ACT employs enables the delivery of targeted radiation that selective and specifically targets immune cells including those implicated in the CAR-T-associated toxicities of neurotoxicity and cytokine release syndrome. We are eager to begin treating patients in this first of its kind pilot study to explore the potential of Iomab-ACT targeted lymphodepletion to modulate the immune system and improve the safety profile of CAR T-cell therapy. We are hopeful this technology may ultimately enhance our ability to deliver CAR T-cell therapies more safely. Positive results from pilot study could have a meaningful impact on the way we condition patients for CAR-T and other adoptive cell therapies, which have transformed the treatment of patients with blood cancers."

Sandesh Seth, Actinium’s Chairman and CEO, said "This is a major milestone for Actinium and one we are very excited by. Adoptive cell therapies like CAR-T and gene therapies have emerged as some of the most promising areas in medicine and hold tremendous promise for patients, many of whom have limited or no treatment options remaining. This promise has led to a large and growing field of therapies where we intend to establish Iomab-ACT as the universal solution for targeted, non-chemotherapy conditioning, that harnesses the power of radiation. With Iomab-B nearing complete enrollment in the Phase 3 SIERRA trial for bone marrow transplant conditioning, starting to treat patients in this Iomab-ACT trial for CAR-T conditioning could not come at a better time. We look forward to continuing to build out our strategic business unit in targeted conditioning to best serve patients seeking potentially curative bone marrow transplant, adoptive cell therapy and gene therapy to improve patient access and outcomes."

About Iomab-ACT

Iomab-ACT targets cells that express CD45, an antigen found on immune cells such as lymphocytes and macrophages as well as leukemia and lymphoma cancer cells and delivers the radioisotope warhead iodine-131 to achieve cell depletion. Iomab-ACT is intended to deplete CD45+ immune cells such as macrophages that are implicated in CAR-T related toxicities and may also have an anti-tumor effect on chemo-refractory cancers. Iomab-ACT is a low dose extension of Actinium’s lead program, Iomab-B, which is being studied in a pivotal Phase 3 trial for targeted conditioning prior to a bone marrow transplant. Preclinical data supporting Iomab-ACT’s application in targeted lymphodepletion prior to ACT such as CAR-T was recently published in the journal Oncotarget (https://www.oncotarget.com/archive/v11/i39/).

In addition, clinical data with trace doses of Iomab-B has shown transient, reversible lymphodepletion in patients and drug clearance pharmacokinetics that fit within the vein-to-vein time of CAR-T manufacturing and administration.

Prothena Announces Proposed Offering of Ordinary Shares

On March 24, 2021 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical company with expertise in protein dysregulation and a pipeline of investigational therapeutics for rare peripheral amyloid and neurodegenerative diseases, reported that it has commenced an underwritten public offering of its ordinary shares (Press release, Prothena, MAR 24, 2021, View Source [SID1234577092]). All of the ordinary shares in the offering will be sold by Prothena. In addition, Prothena has granted the underwriters a 30-day option to purchase up to an additional 15% of the number of ordinary shares sold.

Citigroup, Jefferies, and Cantor are acting as joint book-running managers. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering will be completed, or as to the actual size or terms of the offering.

The proposed public offering will be made pursuant to an automatic shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission (the "SEC") on March 23, 2021 and automatically became effective upon filing. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and available on the SEC’s website located at View Source or may be obtained by contacting Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (800) 831-9146; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at (877) 821-7388, or by e-mail at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 6th Floor New York, NY 10022, or by emailing [email protected].

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

Genprex to Present at the Spring 2021 Oncology Investor Conference on March 29

On March 24, 2021 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that it will present at the Spring 2021 Oncology Investor Conference on March 29, 2021 (Press release, Genprex, MAR 24, 2021, View Source [SID1234577090]). Genprex’s President and Chief Executive Officer, Rodney Varner, will deliver a virtual company overview to investors, including its novel gene therapies for non-small cell lung cancer and diabetes.

Event: Oncology Investor Conference (Virtual)

Date: The conference will take place virtually March 29 – April 2, 2021

Presentation Date: Monday, March 29

Presentation Time: 2 p.m. Eastern Daylight Time

Registration Link: http://bit.ly/3qT3ztc

The Company invites investors to join the webcast presentation, and Mr. Varner will be available for one-on-one meetings with investors throughout the conference.

FORTE BIOSCIENCES, INC. ANNOUNCES 4Q AND FULL YEAR 2020 RESULTS AND PROVIDES A GENERAL BUSINESS UPDATE

On March 24, 2021 Forte Biosciences, Inc. (www.fortebiorx.com) (NASDAQ: FBRX), a clinical-stage biopharmaceutical company reported fourth quarter and full year 2020 results and provides a general business update on March 24, 2021 (Press release, Tocagen, MAR 24, 2021, View Source [SID1234577089]).

"Forte made significant progress in the fourth quarter of 2020. In September, we initiated a randomized trial of FB-401 in atopic dermatitis patients, including adults and children 2 years of age and older. We are very pleased to announce that patient enrollment is now complete. This is a significant milestone that represents the culmination of the entire team’s effort and is particularly impressive in the context of the many challenges associated with the current pandemic. Another notable milestone was the granting of Fast Track designation to FB-401 by the FDA in recognition of the unmet need and seriousness of the disease. Additionally, we strengthened our balance sheet with a successful public offering in November," said Paul Wagner, Ph.D., CEO of Forte Biosciences. "Following the close of the quarter, two additional patents were issued, further bolstering our robust IP protection and bringing the total U.S. patent portfolio to nine."

Fourth Quarter and Full Year 2020 Results

Fourth Quarter Business Highlights

In September 2020, Forte initiated a multi-center, placebo-controlled clinical trial of its lead product candidate, FB-401 which was expected to enroll approximately 124 pediatric, adolescent and adult atopic dermatitis subjects aged 2 years of age and older. Enrollment is now complete with 154 subjects. Additional information about our Phase 2 trial can be found at ClinicalTrials.gov using the identifier NCT04504279.

In October 2020, the U.S. Food and Drug Administration ("FDA") granted Fast Track Designation to FB-401 for the treatment of atopic dermatitis.

On November 2, 2020, Forte completed a public offering of 1,614,035 shares of its common stock at $28.50 per share, which includes the over-allotment option exercised by underwriters to purchase an additional 210,526 shares for gross proceeds of $46.0 million.

Forte ended the year 2020 with approximately $58.8 million in cash and cash equivalents which Forte believes is sufficient to fund operations for at least the next 12 months. Cash burn for the fourth quarter 2020 was $4.1 million. Forte had approximately 12.8 million shares of common stock outstanding as of December 31, 2020. In February 2021, Forte issued 673,463 shares of its common stock pursuant to cashless exercises by certain warrant holders.

Fourth Quarter and Full Year 2020 Operating Results

Research and development expenses were $3.0 million and $1.2 million for the three months ended December 31, 2020 and 2019, respectively, and $10.0 million and $2.7 million for the years ended December 31, 2020 and 2019, respectively. The increases in 2020 were primarily due to manufacturing and clinical development costs as Forte continues to advance FB-401 through Phase 2 clinical trials.

General and administrative expenses were $1.5 million and $0.4 million for the three months ended December 31, 2020 and 2019, respectively, and $4.2 million and $1.4 million for the years ended December 31, 2020 and 2019, respectively. The increases in 2020 were primarily due to professional fees for legal, auditing, tax and business consulting services, and personnel expenses as Forte transitioned to being a public company.

In the second quarter of 2020, Forte recognized a charge of $32.1 million for acquired in-process research and development related to the reverse merger with Tocagen which closed on June 15th, 2020.

Losses per share were $0.37 and $0.74 for the three months ended December 31, 2020 and 2019, respectively, and $6.32 and $1.93 for the years ended December 31, 2020 and 2019, respectively.

Additional detail on our financial results for the full year 2020 can be found in Forte’s Form 10-K as filed with the SEC on March 16, 2021. You can also find more information in the investor relations section of our website at www.fortebiorx.com.

Conference Call and Webcast Information

Forte management will host a conference call and webcast on Wednesday, March 24th at 8:30 AM Eastern Time. Participants may access the call by dialing 877-705-6003 (Domestic) or 201-493-6725 (International). The conference ID number is: 13717632.

Participants may also access the webcast through the following link:

View Source;passcode=13712591&h=true&info=company-email&r=true&B=6

A replay of the call will be available through March 31st from the investor relations section of Forte’s website at View Source or at View Source .