Phio Pharmaceuticals Presents Preclinical Data Demonstrating Synergy-Enhanced in vivo Anti-Tumor Efficacy of PD-1/CTLA-4 Dual-Targeting INTASYL

On April 18, 2023 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology is designed to make immune cells more effective in killing tumor cells, reported that in vivo data from a mouse model of colon cancer demonstrates target synergy-enhanced anti-tumor efficacy from a novel dual-targeting mouse PD-1 and CTLA-4 of an INTASYL coformulation (Press release, Phio Pharmaceuticals, APR 18, 2023, View Source [SID1234630255]).

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Intratumoral administration of the PD-1/CTLA-4 INTASYL improved tumor control compared to either single targeting formulation, at an identical total dose. The dual-targeting formulation was well tolerated.

"The synergistic effects of dual inhibition of PD-1 and CTLA-4 in enhancing tumor response are clinically recognized, however, a high rate of immune-related adverse events limits the utility of systemic use of this combination of products," said Dr. Mary Spellman, Phio’s Acting Chief Medical Officer. "Intratumoral administration of dual-targeting PD-1/CTLA-4 INTASYL may provide an effective treatment option, with an improved safety profile."

Presentation Details:

Poster Title:

INTASYL self-delivering RNAi therapeutic dual targeting PD-1 and CTLA-4
provides synergistic antitumor efficacy in the treatment of murine colon cancer
in vivo

Session Date and Time:

Tuesday, April 18, 2023 from 1:30 PM – 5:00 PM EST

Phio Pharmaceuticals Announces $2 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules

On April 18, 2023 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology is designed to make immune cells more effective in killing tumor cells, reported that it has entered into a definitive agreement for the issuance and sale of an aggregate of 353,983 of its shares of common stock at a purchase price of $5.65 per share in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Phio Pharmaceuticals, APR 18, 2023, View Source [SID1234630254]). In a concurrent private placement, Phio has also agreed to issue and sell unregistered Series A warrants to purchase up to an aggregate of 353,983 shares of common stock and unregistered Series B warrants to purchase up to an aggregate of 353,983 shares of common stock. The offering is expected to close on or about April 20, 2023, subject to the satisfaction of customary closing conditions.

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Logo – View Source

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

Each series of warrants will have an exercise price $5.40 per share and become exercisable immediately upon issuance. The Series A warrants have a term of five and one-half years from the date of issuance and the Series B warrants have a term of eighteen months from the date of issuance.

The gross proceeds to the Company from the offering are expected to be approximately $2 million, before deducting the placement agent’s fees and other offering expenses payable by Phio. Phio currently intends to use the net proceeds from the offering for the development of its immuno-oncology programs, working capital and general corporate purposes.

The shares of common stock offered in the registered direct offering (but excluding the unregistered warrants offered in the concurrent private placement and the shares of common stock underlying such unregistered warrants) are being offered and sold by the Company pursuant to a "shelf" registration statement on Form S-3 (Registration No. 333-256100), including a base prospectus, previously filed with the Securities and Exchange Commission (SEC) on May 13, 2021 and declared effective by the SEC on May 21, 2021. The offering of the shares of common stock to be issued in the registered direct offering are being made only by means of a prospectus supplement that forms a part of the registration statement. A final prospectus supplement and an accompanying base prospectus relating to the registered direct offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the final prospectus supplement and accompanying base prospectus may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

The offer and sale of the unregistered warrants described above are being made in a transaction not involving a public offering and have not been registered under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act") and/or Rule 506(b) of Regulation D promulgated thereunder and, along with the shares of common stock underlying such unregistered warrants, have not been registered under the Securities Act or applicable state securities laws. Accordingly, the unregistered warrants and underlying shares of common stock may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

In connection with the offering and effective upon the closing of the offering, the Company also agreed to amend certain existing warrants to purchase up to an aggregate of 191,619 shares of the Company’s common stock that were previously issued in April 2018 through January 2021 at exercise prices ranging from $26.52 to $2,079.00, such that the amended warrants will have a reduced exercise price of $5.40 per share, at an additional offering price of $0.125 per amended warrant.

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

ORIC Pharmaceuticals Presents Promising Preclinical Data on Two Programs at the 2023 American Association for Cancer Research (AACR) Annual Meeting

On April 18, 2023 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported two preclinical poster presentations at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, ORIC Pharmaceuticals, APR 18, 2023, View Source [SID1234630253]).

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"Our presentations at AACR (Free AACR Whitepaper) reflect the excellent preclinical scientific support of our development pipeline," said Lori Friedman, PhD, chief scientific officer. "Preclinical data provided insights into the comprehensive biomarker strategy for ORIC-944, our PRC2 inhibitor in Phase 1 as a monotherapy for metastatic prostate cancer. We are also pleased with the progress of our PLK4 program, with data showing that the exquisite kinase selectivity is key to synthetic lethality in tumor models with high TRIM37."

Presentation details:

ORIC-944: allosteric inhibitor of PRC2
ORIC-944 is a potent, orally bioavailable, highly selective allosteric small molecule inhibitor of PRC2, the complex which tri-methylates histone H3 lysine 27 (H3K27me3) via targeting the embryonic ectoderm development (EED) subunit, and is in early clinical development as a monotherapy for patients with metastatic prostate cancer.

Poster Presentation:

Biomarker strategy for a phase 1 study of ORIC-944, a potent and selective allosteric PRC2 inhibitor, in patients with metastatic prostate cancer

Key findings of the presentation:

Preclinical pharmacology studies in mice showed that ORIC-944 induces dose- and time-dependent H3K27me3 reduction in the skin epidermis, peripheral blood monocytes, and cell free nucleosomes in plasma, with the latter PD modulation being tumor-specific.
Putative PRC2 target genes were identified via time-dependent transcriptional and epigenetic profiling of xenograft tumor models orally dosed with ORIC-944.
These studies and corresponding assay development support the comprehensive biomarker strategy of target engagement and pharmacodynamic biomarkers implemented in the ongoing Phase 1 trial of ORIC-944 in patients with metastatic prostate cancer.
PLK4 Inhibitor Program
The PLK4 inhibitor program is a small molecule therapeutic program intended to address a mechanism of innate resistance found in a subset of breast cancers, specifically a synthetic lethal interaction of polo-like kinase 4 (PLK4) inhibition in tumors bearing a TRIM37 DNA amplification/elevation. A novel, potent, highly selective, orally bioavailable PLK4 inhibitor was selected as a development candidate in the fourth quarter of 2022.

Poster Presentation:

Selective PLK4 inhibition demonstrates synthetic lethality in TRIM37 amplified neuroblastoma and breast cancer models while less selective inhibitors do not

Key findings of the presentation:

ORIC discovered novel, potent, orally bioavailable small molecule inhibitors of PLK4 that are highly selective, including against the closely related aurora kinases and PLK1-3.
ORIC PLK4 selective inhibitors show greater potency in TRIM37 high cancer cell lines relative to low TRIM37 low cell lines, whereas no differential was observed for non-selective inhibitors.
Apoptotic cell death was observed solely in TRIM37 high cancer cells for ORIC PLK4 selective inhibitors, in contrast to non-selective inhibitors which did not show this synthetic lethality.
Using a genetically engineered PLK4 cell line variant (PLK4 G95L) that prevents compound-mediated inhibition of PLK4, selective PLK4 inhibitors lose activity in TRIM37 high G95L cells, confirming on-target cell activity, compared with non-selective inhibitors whose cell potency is not dependent on PLK4 inhibition.
PLK4 inhibition blocks trans-autophosphorylation and PLK4 protein degradation and correlates with cell viability for selective compounds, and not for non-selective inhibitors.
Together these mechanistic data confirm the potential of highly selective PLK4 inhibition as a synthetic lethal therapy for TRIM37 amplified/elevated cancers.

OncoNano Presents Compelling Data for ONM-501 and a Novel Tumor Specific Delivery Technology at AACR Annual Meeting 2023

On April 18, 2023 OncoNano Medicine, Inc. reported three posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Press release, OncoNano Medicine, APR 18, 2023, View Source [SID1234630252]). The posters detail positive nonclinical data for ONM-501, the Company’s dual-activating STING (STimulator of INterferon Genes) agonist and lead therapeutic development candidate, formulated with the company’s OMNI polymer technology as well as positive data for encapsulated bispecific antibody and cytokine using ON-BOARD tumor specific delivery technology.

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"STING plays a critical role in innate immune response against infection and cancer, and we continue to be pleased with the data which support further advancement of the ONM-501 program," said Ruolan Han, Ph.D., Vice President of Nonclinical & Translational Medicine for OncoNano Medicine. "We look forward to bringing ONM-501 to the clinic this year and furthering the development of OMNI as we work toward our goal of delivering critical treatments to patients in need. Previous preclinical studies have shown that ONM-501 works by stabilizing the STING protein and delivering cGAMP intracellularly, where it is shielded from degradation by ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1). Combining these observations and the immune stimulation with limited systemic toxicity observed in the nonclinical species, we believe that ONM-501 has the potential to show an improved clinical profile as compared to earlier experimental STING agonists."

Previously, ONM-501, a dual-activating STING agonist, has demonstrated the ability to produce a burst and sustained activation of STING signaling that leads to a robust adaptive immune response through a unique polymer-STING binding mechanism which differs from earlier cyclic di-nucleotide (CDN) STING agonist programs. This novel mechanism provides potent anti-tumor efficacy as a monotherapy and in combination with anti-PD1 in multiple preclinical mouse models with both "hot" and "cold" tumor microenvironments. In vivo pharmacodynamic (PD) analysis confirmed STING activation, enhanced tumor lymphocyte infiltration, and tumor PD-L1 upregulation by ONM-501 and demonstrated the target-engagement activity of ONM-501 in multiple species. New pharmacokinetics/biodistribution data presented at the conference in tumor-bearing mice revealed that intratumorally injected ONM-501 showed high tumor retention and very low systemic exposure due to the polymeric micelle formulation, maximizing antitumor efficacy while minimizing systemic toxicity. This new data further differentiates ONM- 501 from other small molecule STING agonist programs. Safety studies in multiple species established a wide therapeutic window for ONM-501 making it a promising candidate for clinical evaluation.

Two additional posters were presented earlier in the conference, reporting encapsulation and masked delivery of Interleukin-12 (IL-12) and T cell engager bispecific antibodies using ON- BOARD. The results demonstrate significantly improved tolerability, anti-tumor efficacy in mice and potential for clinical translation.

"Our ON-BOARD pH-sensitive micelle delivery platform continues to demonstrate improvement of therapeutic indices with a variety of therapeutic protein payloads including the highly potent interleukin-12 and T-cell engagers," said Tian Zhao, Ph.D., Vice President of Research and Development for OncoNano Medicine. "We have seen challenges with other IL-12 and T-cell engager programs related to suboptimal therapeutic index, associated with toxicities related to systemic exposure. In contrast, the tumor-specific delivery of ON-BOARD encapsulated molecules demonstrates a much broader therapeutic window. The promising data that we presented at AACR (Free AACR Whitepaper) 2023 suggest our technology may provide a solution to overcome the clinical application limitations of these highly potent protein therapeutics."

Presentation Overview:

TITLE: Improved tolerability and tumor specific delivery of a therapeutic bispecific T cell engager using a pH-sensitive nanoparticle platform
PRESENTER: Qingtai Su, Ph.D.

TITLE: Encapsulation of IL-12 with an ultra pH-sensitive nanoparticle platform improves tolerability and promotes antitumor response in mice
PRESENTER: Tian Zhao, Ph.D.

TITLE: ONM-501, a dual-activating polyvalent STING agonist, enhances tumor retention and demonstrates favorable preclinical safety profile
PRESENTER: Zirong Chen, Ph.D.

Nouscom Presents New Positive Translational Phase 1b Data of NOUS-PEV, a Personalized Neoantigen Cancer Immunotherapy, in a Late-Breaking Abstract at AACR 2023

On April 18, 2023 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vector immunotherapies, reported new translational and biomarker data obtained from the ongoing Phase 1b trial evaluating NOUS-PEV in patients with metastatic melanoma (Press release, NousCom, APR 18, 2023, View Source;utm_medium=rss&utm_campaign=nouscom-presents-new-positive-translational-phase-1b-data-of-nous-pev-a-personalized-neoantigen-cancer-immunotherapy-in-a-late-breaking-abstract-at-aacr-2023 [SID1234630250]). The data will be presented today in a Late-Breaking session at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

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Dr. Elisa Scarselli, Chief Scientific Officer and Co-Founder of Nouscom, said: "These translational data presented at AACR (Free AACR Whitepaper) demonstrate NOUS-PEV, in combination with pembrolizumab, induces long-lasting, tumor-infiltrating memory T cells and anti-tumor activity in metastatic melanoma patients, further supporting the mechanism of actions driving clinical efficacy. Our results further validate the immunogenic potency of our viral vector platform targeting shared and personalized neoantigens. We look forward to advancing the clinical development of NOUS-PEV and reporting complete Phase 1 results later this year."

The abstract reports a greater than 90% success in manufacturing feasibility with a median vaccine release of 8 weeks from biopsy. NOUS-PEV was demonstrated to be safe, well tolerated and highly immunogenic, inducing potent neoantigen-specific CD4 and CD8 T cell responses that were detected for greater than six months in all evaluable patients. Biomarker analysis demonstrated neoantigen-specific increased T cell migration and infiltration in tumors in patients with durable clinical responses. Current clinical efficacy data from six melanoma patients with 11 months median follow up demonstrated 4 partial responses, 1 durable stable disease and 1 progressive disease.

Poster Presentation Details:

Title: NOUS-PEV, a Personalized Cancer Immunotherapy targeting neoantigens, induces long lasting, tumor infiltrating memory T cells