On October 4, 2024 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, reported a corporate update to provide investors with a deeper understanding of recent data and what is expected for 2025 (Press release, Oncolytics Biotech, OCT 4, 2024, View Source [SID1234647035]).

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"We’re excited by the recent BRACELET-1 results, which exceeded our expectations and substantiate the strong efficacy signal previously observed in breast cancer patients treated with pelareorep," said Wayne Pisano, Interim CEO and Chair of Oncolytics’ Board of Directors. "Having treated well over 100 HR+/HER2- metastatic breast cancer patients in multiple clinical studies, these results provide the basis for a development path leading to an accelerated approval. The BRACELET-1 results, combined with recent feedback from the FDA, give us confidence in our development approach, and we look forward to initiating a clinical trial designed to support the approval of pelareorep as a novel breast cancer therapeutic."

Mr. Pisano continued, "The gastrointestinal cancer data also supports making pancreatic cancer a major priority for the company. To advance this development, we’ve established a collaboration with the Global Coalition for Adaptive Research (GCAR), and The Pancreatic Cancer Action Network (PanCAN) has provided us with the funding to further investigate pelareorep in pancreatic cancer through our GOBLET study. Having demonstrated pelareorep’s efficacy across multiple cancer indications and with important data readouts and future studies on the horizon, I’m looking forward to these next few years of Oncolytics’ growth and development."

Planned HR+/HER2- metastatic breast cancer study could open the door to an accelerated approval

The strong efficacy results from BRACELET-1 provide the foundation for a large Phase 2 study designed to support an accelerated approval. Early in 2025, we plan to submit to the FDA a pelareorep + paclitaxel combination therapy breast cancer trial. The study will enroll approximately 180 patients with HR+/HER2- advanced/metastatic breast cancer who have progressed on antibody-drug conjugates (ADCs) like Enhertu, who are not eligible for ADCs, or who cannot tolerate ADCs, which represents a patient population of approximately 55,000 patients in the US.1-4 The study design has sufficient statistical power to deliver a p-value of < 0.05 with a progression-free survival (PFS) benefit of ≥4.3 months. Notably, the BRACELET-1 study demonstrated a 5.7-month PFS benefit for the pelareorep + paclitaxel arm compared to chemotherapy alone, as detailed below. Enrollment in the registration-enabling study is expected to commence in the first half of 2025.

Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, commented, "With the continuing evolution of breast cancer treatment, we have designed our breast cancer program with the guidance of leading experts in the field. Our first randomized study in breast cancer, IND-213, demonstrated the ability of pelareorep combination therapy to improve survival in heavily pre-treated patients with advanced or metastatic HR+/HER2- disease. The subsequent randomized BRACELET-1 study showed that pelareorep combination therapy could improve outcomes in HR+/HER2- breast cancer patients who had received prior CDK4/6 inhibitors. Based on the success of these studies, we are now ready to pursue a large phase 2 study powered to support an accelerated approval in the setting of ADC therapies such as Enhertu. Our plan is designed to obtain a regulatory approval with fewer patients, in a shorter time, and requiring less funding than traditional regulatory pathways. Our thorough understanding of pelareorep’s mechanism of action makes us confident that pelareorep-based combination therapy will continue to deliver strong clinical benefits to HR+/HER2- breast cancer patients within the current treatment approach."

BRACELET-1 efficacy data in HR+/HER2- metastatic breast cancer

The recently reported final BRACELET-1 study results provide clear evidence of pelareorep’s ability to improve outcomes in patients with advanced breast cancer (link to press release). Patients in the paclitaxel control arm had a median overall survival of 18.2 months. However, more than half of the patients in the pelareorep combination therapy arm were still alive at the time of the final survival analysis, resulting in a median overall survival of "Not Reached." A conservative estimate of median overall survival for the pelareorep arm is 32.1 months, demonstrating that pelareorep + paclitaxel delivered a greater than 12-month survival advantage compared to paclitaxel alone. This survival benefit is further illustrated by the 24-month overall survival rate, which showed that 64% of patients treated with pelareorep combination therapy survived at least 2 years compared to only 33% of patients treated with paclitaxel alone. In addition, final progression-free survival was 12.1 months for pelareorep + paclitaxel compared to 6.4 months for paclitaxel alone, yielding a benefit of 5.7 months.

Gastrointestinal cancer opportunities

We also anticipate continuing our development of pelareorep in gastrointestinal cancers. Once the master protocol has been finalized with GCAR for the pelareorep combination therapy, we intend to approach the FDA before the end of the year. This study is designed to produce registrational data. Additionally, we continue to evaluate pelareorep combination therapy in patients with anal cancer, building on the promising initial efficacy data in this patient population. If the expanded results continue to show a favorable efficacy signal, we anticipate moving directly to a registration-enabling study. Finally, we expect to provide updates on cohort 5 of the GOBLET study, which is investigating pelareorep in pancreatic cancer in combination with the chemotherapy modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab. Positive results from this combination will bolster our opportunity in pancreatic cancer and potentially provide an additional registrational opportunity. The initial efficacy results from this cohort are expected in the second half of 2025.

Anticipated upcoming milestones
•H1 2025: Initiate registrational study of pelareorep + paclitaxel in HR+/HER2- metastatic breast cancer
•H1 2025: Safety run-in data from cohort 5 of the GOBLET study, investigating pelareorep and mFOLFIRINOX with or without atezolizumab in newly diagnosed pancreatic cancer
•H1 2025: updated efficacy data from cohort 4 of the GOBLET study, investigating pelareorep and atezolizumab in second-line or later anal cancer
•H2 2025: Initial efficacy results from cohort 5 of the GOBLET study, investigating pelareorep and mFOLFIRINOX with or without atezolizumab in newly diagnosed pancreatic cancer

On October 4, 2024 Onchilles Pharma, a private biotech company developing pan-cancer therapeutics that leverage the ELANE pathway, a novel innate immune mechanism of action for potent and selective cancer killing, reported that it will present new preclinical data for its NEU-002 program for systemic delivery at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Onchilles Pharma, OCT 4, 2024, View Source [SID1234647034]). The meeting will be held both virtually and at the George R. Brown Convention Center in Houston from November 8-10, 2024.

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Presentation Details

Poster Title: NEU-002 leverages a cancer-specific innate immune pathway to induce immunogenic cell death and stimulate anti-tumor immunity

Abstract Number: 1297

Date and Time: Friday, November 8, 2024, 9:00 a.m. to 7:00 p.m. CST

Location: George R. Brown Convention Center, Level 1, Exhibit Halls AB or at View Source

About the NEU-002 Program and the ELANE Pathway

Onchilles’ scientific founder, Dr. Lev Becker, discovered that human neutrophils release neutrophil elastase (ELANE), which selectively and potently kills cancer cells while sparing healthy cells. This novel innate mechanism of action, known as the ELANE pathway, was published in the journal Cell in 2021. Targeting the ELANE pathway enables the eradication of cancer cells regardless of their genetic makeup, anatomical origin, or immune status. Building on these findings, Onchilles has developed NEU-001 (N17350) for intratumoral delivery and NEU-002 for intravenous delivery and has generated an extensive preclinical dataset showing strong monotherapy efficacy across many tumor types. This efficacy is mediated by immunogenic cancer cell death and mobilization of the immune system, leading to durable responses in preclinical mouse models.

On October 4, 2024 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vector-based cancer vaccines targeting neoantigens, reported that updated safety data, as well as compelling immunogenicity and durability of T cell response from its Phase 1b/2 study evaluating NOUS-209 in Lynch Syndrome carriers will be presented at the 39th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 annual meeting (6th – 10th November 2024, Houston, TX, USA) (Press release, NousCom, OCT 4, 2024, View Source;utm_medium=rss&utm_campaign=nouscom-to-present-updated-positive-data-on-nous-209s-potential-to-intercept-cancer-in-lynch-syndrome-carriers-at-sitc-2024 [SID1234647033]).

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NOUS-209 is an innovative and unique off-the-shelf vaccine encoding 209 neoantigens that are shared across sporadic and hereditary Microsatellite Instable (MSI) tumors. Lynch Syndrome (LS) is one of the most prevalent hereditary cancer syndromes affecting approximately one in 300 people. LS carriers have a high-risk predisposition to developing MSI tumors with an up to 80% lifetime risk of developing colorectal cancer (CRC). Currently, there are no treatment options for LS carriers, other than active surveillance and / or prophylactic surgery. NOUS-209 monotherapy has the potential to ‘intercept’ cancer before it occurs in these individuals.

Interim results in the first ten LS participants from a Phase 1b/2 study (NCT05078866) were reported in a late-breaking abstract and presented at the SITC (Free SITC Whitepaper) 2023 demonstrating good safety and robust and broad CD4 and CD8 T cell immunity of NOUS-209 monotherapy (D’Alise et al.1).

Abstract details are as follows:

Abstract Title: Nous-209 vaccine induces shared neoantigen immunogenicity for cancer interception in healthy Lynch Syndrome carriers: results from Phase Ib/II trial
Abstract Number: 638
Presenter: Dr Eduardo Vilar

NOUS-209 is also being evaluated in a randomized, global multicenter Phase 2 trial for the treatment of deficient mismatch repair (dMMR)/MSI-High tumor patients with unresectable or metastatic CRC in combination with pembrolizumab (NCT04041310).

On October 4, 2024 Biodexa Pharmaceuticals PLC ("Biodexa" or "the Company"), (Nasdaq: BDRX), a clinical stage biopharmaceutical company developing a pipeline of innovative products for the treatment of diseases with unmet medical needs reported an update in respect of its open label Phase 1 study of MTX110 in recurrent glioblastoma (Press release, Biodexa Pharmaceuticals, OCT 4, 2024, View Source [SID1234647032]).

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In October 2023, the Company announced completed recruitment of four patients into cohort A of its Phase 1 study of MTX110 (also known as MAGIC-G1 study)(NCT 05324501) in patients with recurrent glioblastoma (rGBM).

MAGIC-G1 is an open-label, dose escalation study designed to assess the feasibility and safety of intermittent infusions of MTX110 administered by convection enhanced delivery (CED) via implanted refillable pump and catheter. Patients received MTX110 via intermittent repeated CED infusions. As of today, the status of patients in Cohort A is as follows:

Patients #1 and #2 have deceased with overall survival (OS) since start of treatment of 12 months and 13 months, respectively.

Patients #3 and #4 remain in post-study follow-up. Patient #3 had progression free survival (PFS) of six months and OS thus far of 13 months since start of treatment. Patient #4 has not yet had confirmed progression and, as of today, has PFS and OS of 12 months since start of treatment.

Glioblastoma (GBM) is the most aggressive central nervous system (CNS) primary malignancy in adults with an annual incidence is approximately 3 per 100,000 population. The standard of care in newly diagnosed GBM includes maximal safe surgical resection, followed by concurrent radiotherapy and temozolomide (TMZ). GBM virtually always recurs with median PFS of 1.5–6.0 months and median OS of 2.0–9.0 months (source: Birzu et al. View Source).

These interim data in rGBM build on the data announced by the Company on July 2, 2024, and presented at the recent 21st International Symposium on Paediatric Neuro-Oncology (ISPNO 2024) of a Phase 1 study of MTX110 in nine patients with Diffuse Midline Glioma ("DMG") which showed, after only two infusions and a single patient at optimum dose, median OS of 16.5 months. In an earlier Phase 1 study conducted by the University of California San Francisco of MTX110 in seven patients with DMG which showed median OS of 26.1 months. These data compare favorably with median OS in a cohort of 316 cases of 10.0 months (source: Jansen et al, 2015. Neuro-Oncology 17(1):160-166).

About MTX110
MTX110 is a water-soluble form of panobinostat free base, achieved through complexation with hydroxypropyl-β-cyclodextrin (HPBCD), that enables convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumor. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak) is not suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations. Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for recurrent glioblastoma (NCT05324501) and recurrent medulloblastoma (NCT04315064). MTX110 is delivered directly into and around the patient’s tumor via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumor to very high drug concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects. Panobinostat has demonstrated high potency against DIPG (DMG) and GBM tumor cells in in vitro and in vivo models, and in a key study it was the most promising of 83 anticancer agents tested in 14 patient-derived DIPG (DMG) cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).

On October 4, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors or hematologic malignancies, reported that three abstracts highlighting its pipeline of clinical product candidates and anti-exhaustion technology have been accepted for presentation at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) taking place in Houston, TX, Nov. 6-10, 2024 (Press release, Lyell Immunopharma, OCT 4, 2024, View Source [SID1234647031]).

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The three presentations highlight anti-exhaustion technology and product candidates being advanced in Lyell’s pipeline of cell therapies for solid tumors and hematologic malignancies, including the first presentation at a scientific conference of translational data from the LYL797 Phase 1 clinical trial demonstrating solid tumor infiltration and cell killing by reprogrammed ROR1 CAR T cells.

Details of the poster presentations are below:

LYL797 ROR1 CAR T-cell Translational Data Demonstrated T-cell Reprogramming Limited Exhaustion, Maintained Stemness, and Resulted in Tumor Infiltration and Cell Killing in Patients with Solid Tumors

Abstract Number: 285
Presentation Date & Time: Friday, Nov. 8, 2024, 12:15-1:45 p.m. and 5:25-6:55 p.m.
Multiomic profiling of LYL119: A Reprogrammed ROR1 CAR T Product Generates T cells with Reduced Exhaustion and Enhanced Memory Characteristics Associated with Increased AP-1 and Reduced NR4A Bindings

Abstract Number: 283
Presentation Date & Time: Friday, Nov. 8, 2024, 12:15-1:45 p.m. and 5:25-6:55 p.m.
Utilizing Stim-R Technology to Reduce Irradiated Feeder Cells in the Tumor Infiltrating Lymphocyte Culture Process

Abstract Number: 440
Presentation Date & Time: Saturday Nov. 9, 2024, 12:00-1:30 p.m. and 7-8:30 p.m.