On November 3, 2023 Prime Medicine, Inc. (Nasdaq: PRME), a biotechnology company committed to delivering a new class of differentiated one-time curative genetic therapies, reported financial results and provided business updates for the third quarter ended September 30, 2023 (Press release, Prime Medicine, NOV 3, 2023, View Source [SID1234636893]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In recent weeks, we announced compelling preclinical data across our pipeline, including our first in vivo demonstration of Prime Editing in non-human primates. The consistency of these data provides proof-of-concept that our technology can precisely and efficiently edit across a range of target tissues, correcting pathogenic mutations at levels that may be sufficient to reverse disease manifestations across severe genetic conditions," said Keith Gottesdiener, M.D., President and Chief Executive Officer of Prime Medicine. "We also shared presentations detailing the power of our proprietary delivery systems, as well as new off-target analyses demonstrating the potentially best-in-class safety profile of Prime Editors. Together, these encouraging results mark meaningful progress toward the clinic and support our strategy of simultaneously advancing multiple programs forward. We look forward to leveraging the modularity of our platform, as well as our many clinical, manufacturing and regulatory learnings, to inform further development of our pipeline with the goal of delivering one-time, curative therapies to transform the lives of patients with a wide spectrum of debilitating diseases."
Recent Business Updates

Prime Medicine is advancing a strategic pipeline of eighteen programs. The Company is initially focused on indications with the opportunity for the fastest, most direct path to the clinic and technical success in humans, as well as indications that cannot be treated using other gene editing approaches.

Chronic Granulomatous Disease (CGD)

•In August 2023, Prime Medicine received Rare Pediatric Drug designation (RPDD) from the U.S. Food and Drug Administration (FDA) for PM359. The FDA grants RPDD to medicines intended for the treatment of serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the United States. Companies that receive approval for a New Drug Application or Biologics License Application for a rare pediatric disease may be eligible to receive a voucher for priority review of a subsequent marketing application for a different product. The priority review voucher may be used by the Company or sold to a third party.
Glycogen Storage Disease 1b (GSD1b)

•In October 2023, Prime Medicine presented new in vivo data at the European Society of Gene and Cell Therapy 2023 Congress, demonstrating the ability of Prime Editors to precisely correct one of the most prevalent disease-causing mutations of GSD1b in both non-human primate (NHP) and mouse models. In these preclinical studies using single lipid nanoparticle (LNP) administration, Prime Editors showed up to 50% whole liver precise editing in NHPs (resulting in up to 83% of the key target cells, liver hepatocytes, edited), with no observed safety concerns. In addition, no detectable off-target effects were observed following a comprehensive in vitro off-target screening analysis. These data, the first evidence of Prime Editing in NHPs, provide proof-of-concept for Prime Medicine’s LNP liver-targeted delivery approach and support the further advancement of the Company’s Prime Editors for liver-targeted programs. Read the full data here.
Retinitis Pigmentosa / Rhodopsin
•In October 2023, Prime Medicine presented new in vivo data at the International Symposium on Retinal Degeneration, demonstrating that Prime Editors can efficiently and precisely correct the predominant mutations that cause rhodopsin associated autosomal dominant retinitis pigmentosa (RHO adRP). In preclinical studies, single Prime Editors showed up to 70% precise correction in photoreceptors, as well as favorable tolerability. These data suggest that Prime Medicine’s proprietary dual adeno-associated virus platform can effectively deliver Prime Editors to the eye, with the potential to treat a range of retinal diseases. Read the full data here.
Additional Pipeline and Prime Editing Platform Updates
•Prime Medicine presented additional preclinical data across its Prime Editing pipeline and technology at several healthcare industry conferences in October and has plans to share additional abstracts at medical meetings before year-end. Highlights of the conference presentations included:
◦An overview of Prime Medicine’s comprehensive suite of assays to identify potential off-target events, which has been expanded to include new, unbiased genome-wide tools. These analyses continue to demonstrate minimal to no detectable off-target edits, chromosomal rearrangements or translocations. These preliminary analyses, across multiple editing programs, suggest potentially best-in-class safety;
◦The first presentation on Prime Medicine’s universal LNP-RNA platform designed to deliver Prime Editors to correct pathogenic mutations in the liver;
◦An update on using Prime Editors for the potential treatment of repeat expansion diseases, including an update on Fragile X syndrome; and
◦Initial proof-of-concept data for Prime Medicine’s hotspot approach to developing Prime Editors to correct the CFTR gene in patients with Cystic Fibrosis, as well as new detail on Prime Medicine’s LNP and all-RNA delivery approaches for the lung.
•In December, Prime Medicine will present preclinical data showcasing the potential of the PASSIGE platform to multiplex edit CAR-T cells at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, being held December 9-12, 2023, in San Diego, CA. Details of the poster presentation are as follows:
Abstract Title: Multiplex Prime Editing and PASSIGE for Non-Viral Generation of an Allogeneic CAR-T Cell Product
Date & Time: Monday, December 11, 6-8 PM PT
Room: San Diego Convention Center, Halls G-H
Session Title: Cellular Immunotherapies: Basic and Translational
Presenter: Emily Pomeroy
Corporate
•In October 2023, the U.S. Patent and Trademark Office issued Prime Medicine’s third patent, No. 11,795,452, "Methods and Compositions for Editing Nucleotide Sequences," which covers Prime Editing systems that include a PEgRNA, Prime Editor protein, and, optionally, a recombinase.

Anticipated Upcoming Milestones

Year-to-date, Prime Medicine continues to make significant progress, executing against key initiatives to drive its Prime Editing platform forward. The Company initiated IND-enabling studies for PM359 in CGD, and expanded preclinical proof-of-concept data in vivo and in vitro across several programs and target tissue types. In addition, as evidenced by in vivo data shared in recent presentations, Prime Medicine continues to optimize its non-viral and viral delivery systems, and to demonstrate excellent off-target profiles for its Prime Editing programs.
Prime Medicine expects the following activities and next steps to drive the Prime Editing platform forward in the coming months:
Pipeline
•Complete first IND filing as early as 2024 with additional IND filings anticipated in 2025.
Platform
•Expand Prime Editing using proprietary recombinase technologies for new and existing programs.
•Maximize Prime Editing’s broad therapeutic potential and create value through strategic business development that extends the reach and impact of Prime Editing to areas beyond Prime Medicine’s current areas of focus.
Third Quarter 2023 Financial Results:
•R&D Expenses: Research and development (R&D) expenses were $41.0 million for the three months ended September 30, 2023, as compared to $25.0 million for the three months ended September 30, 2022. This increase was primarily due to increases in lab supplies, personnel, and facilities costs as the Company continues to expand and build out its R&D activities and function.

•G&A Expenses: General and administrative (G&A) expenses were $10.5 million for the three months ended September 30, 2023, as compared to $6.6 million for the three months ended September 30, 2022. This increase was primarily due to an increase in professional and consultant costs and personnel costs primarily attributable to the build-out of the Company’s G&A team to support its R&D function.
•Net Loss: Net loss was $50.7 million for the three months ended September 30, 2023, as compared to $29.4 million for the three months ended September 30, 2022.
•Cash Position: As of September 30, 2023, cash, cash equivalents, investments and restricted cash were $178.8 million, as compared to $307.4 million as of December 31, 2022.

Financial Guidance

Based on its current operating plans, Prime Medicine expects that its cash, cash equivalents and investments as of September 30, 2023, will be sufficient to fund its operating expenses and capital expenditure requirements through the end of 2024.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.