On November 3, 2023 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported that it has entered into agreements with certain holders of its existing warrants exercisable for 2,130,000 shares of its common stock, in the aggregate, to exercise their warrants at a reduced exercise price of $0.78 per share, in exchange for new warrants as described below (Press release, Panbela Therapeutics, NOV 3, 2023, View Source;utm_medium=rss&utm_campaign=panbela-announces-exercise-of-warrants-in-a-private-placement [SID1234636891]). The aggregate gross proceeds from the exercise of the existing warrants is expected to total approximately $1.9 million, before deducting financial advisory fees. The reduction in the exercise price of the existing warrants and the issuance of the new warrants was structured as an at-market transaction under Nasdaq rules.

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Roth Capital Partners is acting as the company’s financial advisor for this transaction.

The shares of common stock issuable upon exercise of the existing warrants are registered pursuant to a registration statement on Form S-1 (File No.333-271729) which was declared effective by the Securities and Exchange Commission ("SEC") on June 15, 2023.

In consideration for the immediate exercise of the existing warrants for cash and the payment of $0.125 per share underlying the existing warrants, the exercising holders will receive new warrants to purchase shares of common stock in a private placement pursuant to Section 4(a)(2) of the Securities Act of 1933, as amended (the "1933 Act"). Subject to the receipt of stockholder approval for the issuance of the underlying shares of common stock, the new warrants will be exercisable into an aggregate of up to 4,260,000 shares of common stock, at an exercise price of $0.78 per share and have a term of exercise equal to five years after stockholder approval. The new warrants and underlying shares of common stock have not been registered under the Securities Act of 1933, as amended, or applicable state securities laws. Accordingly, the securities may not be offered or sold 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. As part of the transaction, the company has agreed to file a resale registration statement with the SEC to register the resale of the shares of common stock underlying the new warrants.

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

On November 3, 2023 OncoNano Medicine, Inc. reported positive preclinical data describing the effective delivery of interleukin-12 (IL-12) with the ON-BOARD platform technology at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, OncoNano Medicine, NOV 3, 2023, View Source [SID1234636890]).

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The study findings show that encapsulation of a therapeutic IL-12 fusion protein (IL-12Fc) for tumor specific delivery and pH-dependent activation was achieved using the ON-BOARD polymeric micelle technology. The study also found that ON-BOARD significantly improved the tolerability of IL-12Fc, as compared to unencapsulated IL-12. The encapsulated IL-12Fc demonstrated potent anti-tumor efficacy and durable anti-tumor memory in the MC38 colorectal cancer model. ONM-412, the development product candidate with the IL-12 encapsulated in the ON-BOARD polymeric micelle system, is advancing through IND-enabling activities.

"These findings underscore the potential application of the ON-BOARD polymeric micelle system for the delivery of IL-12 as an anti-tumor agent," said Tian Zhao, PhD, Vice President of Research and Development at OncoNano. "We look forward to the continued development of ONM-412 and the ONBOARD platform as a potential technology for the targeted delivery of therapeutics to benefit cancer patients."

The data presented demonstrated that:

ON-BOARD enables murine and human IL-12Fc encapsulation with favorable stability and pH-responsive IL-12 bioactivity in vitro in a HEK reporter assay and in primary cell IFNγ induction. Compared to a protease cleavable masked IL-12, the ON-BOARD formulation shows rapid and complete activation over a short period of time.
ON-BOARD encapsulated IL-12Fc exhibited potent anti-tumor efficacy and prolonged survival in MC38 tumor-bearing animals with long-term memory effect.
ON-BOARD formulation demonstrated effective IL-12 signaling in the tumor as evidenced by activation of CD8 T cells and NK cells; increased levels of IFNγ were seen in the tumor but not systemic circulation.
Reduced systemic exposure was observed with ON-BOARD encapsulated IL-12Fc with a significant improvement in the tolerability as evidenced by reduced body weight loss, normal plasma transaminase levels for liver function, reduced splenomegaly, and reduced systemic free IL-12 levels and IL-12 related cytokines when compared to unencapsulated IL-12Fc.

Presentation Details

TITLE: Encapsulation of IL-12 with an ultra pH-sensitive tumor delivery platform improves tolerability and promotes antitumor response in a preclinical model
PRESENTER: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine
POSTER NUMBER: 1147-B

On November 3, 2023 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a clinical-stage immunotherapeutics company focused on oncology, reported the presentation of a poster that provides further positive translational data from the previously completed AWARE-1 breast cancer window-of-opportunity study, sponsored by SOLTI-Innovative Cancer Research, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting (Press release, Oncolytics Biotech, NOV 3, 2023, View Source [SID1234636889]).

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"Using the novel IMC technology to conduct further translational data analysis from the AWARE-1 study in early-stage breast cancer patients has confirmed and expanded our understanding of pelareorep’s mechanism of action in the tumor microenvironment," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics. "We look forward to incorporating these important translational learnings into our registrational program for HR+/HER2- metastatic breast cancer. These findings likely also have implications for other indications where we have seen signals of efficacy with atezolizumab/pelareorep combinations, including pancreatic cancer in the GOBLET study focused on gastrointestinal cancers."

Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, commented, "Previously published analyses from AWARE-1 patient samples showed that in the first three days after dosing, pelareorep upregulated tumor PD-L1 expression in the tumors, induced the generation and expansion of T cell clones, and promoted the tumor infiltration of CD8+ T cells. It also led to an increase in the CelTIL score in most patients, which is a measure of tumor cellularity and immune infiltration that is associated with favorable clinical outcomes. The new IMC data presented today show an increase in cytotoxic T cells and PD-L1 expression in tumors by three days following treatment and demonstrate pela’s ability to induce an enhanced immune state within tumors. This supports pelareorep’s ability to modify the tumor microenvironment and enhance the responsiveness of cancers to checkpoint inhibitor therapy."

Summary of Data and Findings for Expanded Translational Analysis of the AWARE-1 Study:

Samples: From the AWARE-1 window-of-opportunity study of patients with early-stage HR+/HER2- breast cancer:
•Collected from cohort 2 patients who received pelareorep plus letrozole and atezolizumab (n=10)
•Tumor biopsies were collected on Day 1 (pretreatment), Day 3 (prior to atezolizumab) and Day 21 (when tumors were surgically removed)

Evaluation process:
•Samples were evaluated using a biomarker panel of 37 conjugated antibodies that bind to tumor antigens and immune cells
•The novel IMC technology was used to visualize cellular interactions down to the single cell level

Results: Visualization of the data shows that pelareorep treatment changed the number of PD-L1 tumor cells and the architecture of the tumor microenvironment:
•By Day 3, an increase in PD-L1 positivity and cytotoxic T cells could be seen at a higher rate of tumor infiltration relative to baseline.

About AWARE-1

AWARE-1 was an open-label window-of-opportunity study in early-stage breast cancer. The study combined pelareorep, without or with atezolizumab, and the standard of care therapy according to breast cancer subtype. Tumor tissue was collected from patients as part of their initial breast cancer diagnosis, again on day three following initial treatment, and finally at three weeks following treatment, on the day their tumor is surgically resected. Key objectives of the study were to confirm that pelareorep is acting as a novel immunotherapy, to evaluate potential synergy between pelareorep and checkpoint blockade, and to collect biomarker data. The primary endpoint of the translational study was overall CelTIL score (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study included safety and tumor and blood-based biomarkers. AWARE-1 met its primary endpoint of overall CelTIL score in 2021 (link to the PR, link to the poster). Additional biomarker data announced in 2022 showed pelareorep’s potential to improve the prognosis of breast cancer patients (link to the PR, link to the poster).

Poster Information
Poster Title Analysis of the HR+/HER2- breast cancer tumor microenvironment following immune priming with pelareorep and atezolizumab using imaging mass cytometry – Results from the AWARE-1 trial
Abstract Number 582
Poster Date & Time November 4, 2023 from 9 a.m. – 8:30 p.m. Pacific Time

A copy of the poster is available on the Oncolytics website and can be found by clicking here.

On November 3, 2023 Onchilles Pharma, a private biotech company developing cancer therapeutics that leverage a novel mechanism of action, reported the presentation of new preclinical data for N17350 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting being held virtually and at the San Diego Convention Center from November 1-5, 2023 (Press release, Onchilles Pharma, NOV 3, 2023, View Source [SID1234636888]). The data presented show the potential for N17350, a first-in-class biologic therapeutic inspired by the immunobiology of neutrophils, to become a major new treatment modality for a wide range of cancer types.

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"Our lead drug candidate, N17350, shows a unique combination of potent and selective cancer cell killing and immune activation with the potential to eradicate tumors irrespective of their genetic makeup and anatomical origin," said Lev Becker, Ph.D., Scientific Founder and Board Member of Onchilles Pharma. "These new data presented at SITC (Free SITC Whitepaper) reveal the efficacy of N17350 in difficult-to-treat human xenograft models and establishes a correlation between N17350’s efficacy and elevated histone H1 levels, which are upregulated in cancer cells."

New data presented at SITC (Free SITC Whitepaper) 2023 includes evidence of N17350’s ability to regress tumor growth in a human xenograft model of patient-derived ovarian cancer cell lines as well as colon, lung, and prostate cancers. This builds upon previously presented data at AACR (Free AACR Whitepaper) 2023 showing N17350 efficacy in syngeneic colon (CT26) and metastatic breast (4T1) cancer models. To understand histone H1’s role in this novel mechanism of action, Onchilles’ scientists compared histone H1 levels in cancer cells to non-cancer cells. The results showed that histone H1 levels were elevated in cancer cells and correlated with N17350’s efficacy. Additional data demonstrate that N17350 selectively kills a wide range of cancer cells including those isolated from donor tissue of ovarian cancer patients. Taken together, these findings support a potential broad therapeutic window for this innovative cancer cell-killing mechanism.

"The new preclinical data reported further highlights the broad clinical potential of our lead candidate, N17350, for a wide range of cancer types," said Court R. Turner J.D., Co-Founder and Executive Chair of Onchilles Pharma. "We are on track with our preclinical development efforts which will support advancing N17350 to the clinic next year in skin cancers, head and neck cancer, and triple-negative breast cancer, where treatment options are extremely limited."

About N17350 and Its Novel Mechanism of Action
First described in research published in Cell from the lab of Onchilles’ Co-Founder Lev Becker, human neutrophils release catalytically active neutrophil elastase (called ELANE), which selectively and potently kills cancer cells independent of their genetics and anatomical origin, mobilizes adaptive immunity, and avoids resistance mechanisms. The team at Onchilles translated this ground-breaking discovery into a proprietary set of molecules, including N17350, with the potential to treat a wide variety of tumor types with an optimal efficacy and safety profile.

On November 3, 2023 Integral Molecular, a leading biotech company specializing in antibody discovery against undruggable protein targets reported multispecific molecules targeting GPRC5D, BCMA, and CD3 this week during the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) conference in San Diego (Press release, Integral Molecular, NOV 3, 2023, View Source [SID1234636887]).

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Recent clinical data demonstrate that combination therapy of T cell engaging molecules individually targeting GPRC5D and BCMA on tumor cells offers unprecedented therapeutic benefits in relapsed/refractory multiple myeloma patients. A trispecific antibody that simultaneously engages these molecules while activating T cells is expected to provide comparable and additional benefits as a monotherapy.

Integral Molecular’s oncology drug discovery program has yielded a panel of high affinity bispecific and trispecific molecules targeting GPRC5D, a GPCR target with complex structural biology. The molecules show picomolar cell-killing activity and are highly selective for their targets.

"For decades we have navigated the complexities of molecules like GPRC5D, successfully discovering antibodies against even the most challenging targets," said Joseph Rucker, PhD, VP of R&D at Integral Molecular. "In just a few short months we were able to simultaneously target GPRC5D and BCMA, and we expect to rapidly advance this molecule into preclinical studies."

The company leveraged its MPS antibody discovery platform to discover and engineer antibodies for this program. MPS is unique from other platforms in the use of RNA, DNA, and virus-like particles (VLPs, or Lipoparticles) to present properly folded membrane proteins, and the use of divergent species (chickens) to generate diverse antibody responses.

Dr. Rucker will present the company’s bi- and trispecific GPRC5D antibodies in a poster during the SITC (Free SITC Whitepaper) 2023 conference. GPRC5D and other antibody assets from Integral Molecular are available for licensing.