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TME Pharma Provides Positive Update on 18-Month Survival for NOX-A12 Combination Regimen in Brain Cancer and Provides Strategic Update Including Decision to Engage with US FDA

On October 10, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported a positive update on survival at 18 months for patients receiving NOX-A12 with the VEGF inhibitor bevacizumab and radiotherapy, and provides an overview on upcoming clinical development plans for NOX-A12 in the aggressive adult brain cancer, glioblastoma (Press release, TME Pharma, OCT 10, 2023, View Source [SID1234635840]).

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The percentage of patients who were alive 18 months after start of therapy of NOX-A12 with the VEGF inhibitor bevacizumab and radiotherapy is currently 50% (with the possibility to increase to 67% with the next patient reaching 18 months) which exceeds by 10-fold the 18-month survival of 5% observed in the matched group of patients receiving standard of care1. Since neither bevacizumab (anti-VEGF) alone, nor bevacizumab plus radiotherapy have previously shown to extend survival, the strong increase in survival can be attributed to the complementary mechanism of action of NOX-A12 with bevacizumab and radiotherapy2. The survival rate of the NOX-A12 triple combination also exceeds the 18-month survival of 20% seen in the patients with high levels of the NOX-A12 predictive biomarker EG12 receiving NOX-A12 + radiotherapy alone3, which further supports NOX-A12’s potential to synergize with VEGF inhibition in glioblastoma (see figure below).

The median overall survival has now reached 18 months and is expected to improve further as the remaining patients continue to receive treatment or follow-up care4. Two of the three living patients are clinically stable despite radiographic tumor progression at last report from treating clinicians, including the patient who achieved complete response, now completing 22 months therapy. As a reminder, the matched standard of care reference cohort achieved a median overall survival of 10.5 months.

The NOX-A12-based therapy has now delivered median overall survival exceeding all the relevant competitor studies conducted in the US or EU involving newly diagnosed, chemotherapy-resistant (MGMT unmethylated) glioblastoma patients despite recruiting more difficult to treat patients whose tumors could not be fully removed by surgery5. NOX-A12 in combination with bevacizumab and radiotherapy continues to show an excellent safety and tolerability profile similar to that noted in previous publications.

In the upcoming 6 months the key regulatory steps for NOX-A12 program in brain cancer will include the following:

Q4 2023 – Request advice in October from US Food and Drug Administration (FDA) on next trial design and eligibility for expedited regulatory pathways, such as Fast-Track Designation. Feedback expected in late December.
Q1 2024 – Submit IND6 application for glioblastoma with the US FDA along with expedited regulatory pathway access request. Successful IND filing and feedback targeted by end of Q1 2024.
TME Pharma plans to keep the market updated on the progress of these regulatory discussions. The goal is to have an FDA approved clinical trial protocol in glioblastoma with an expedited regulatory path by the beginning of April 2024 in order to secure the funding for the necessary clinical trial via partnership, investment or other strategic transaction types.

"We believe that survival data from the NOX-A12 bevacizumab expansion arm is now sufficiently mature and have made the decision to request advice from the US regulatory authority in the coming weeks. Once we have feedback from the FDA, we plan to submit an IND and request access to an expedited pathway for approval. We believe that having a clear path to marketing approval in brain cancer, validated by FDA, will significantly increase the attractiveness of NOX-A12 to investors and potential partners." said Aram Mangasarian, CEO of TME Pharma. "While we believe that the FDA will request a randomized clinical trial examining two doses of NOX-A12 combined with bevacizumab and radiotherapy and to compare these two dose regimens against standard of care as a next step, they may also request that these two doses of NOX-A12 be tested only with radiotherapy (without bevacizumab) in order to quantify precisely the benefit of the combination with NOX-A12 and bevacizumab, which would add two additional arms to the clinical trial. We anticipate that an additional trial or an expansion of the upcoming trial would be required for full approval."

BPGbio to Share Updates in Development of Late-Stage AI-Developed Therapeutic Pipeline at the Pharma Partnering Summit

On October 10, 2023 BPGbio, Inc., a leading AI-powered biopharma that focuses on oncology, neurology, and rare diseases, reported plans to present on their groundbreaking AI-developed therapeutics portfolio at the upcoming Pharma Partnering Summit in Boston October 19-20, 2023 (Press release, BPGbio, OCT 10, 2023, View Source [SID1234635839]). At the meeting, BPGbio’s President and CEO, Dr. Niven R. Narain, and Executive Chairman Daniel Elliott will unveil the progress made in advancing their oncology drug candidate BPM31510, currently under investigation for glioblastoma multiforme (GBM) and pancreatic cancer. They will also provide insights into the company’s growing portfolio of AI-discovered therapeutics and diagnostics, identified through the company’s proprietary NAi Interrogative Biology Platform.

"We are excited to share with industry peers, partners and the investment community about BPGbio’s AI-driven late stage clinical assets at the Pharma Partnering Summit," said Niven R. Narain, Ph.D., President & CEO, BPGbio, Inc. "The positive progress we are making in our clinical trials continue to validate the efficacy of our AI powered NAi Interrogative Biology Platform, with our lead oncology candidatbusine, BPM31510, demonstrating an early indication for potential clinical benefit for both GBM and pancreatic cancer—two of the most aggressive and deadly cancers."

BPM31510, the company’s lead drug candidate is a small molecule compound currently in a Phase 2b clinical trial led by Stanford for glioblastoma multiforme GBM. Notably, BPM31510 has also garnered a favorable recommendation from the medical advisory board to progress into Phase 2b trials for pancreatic cancer. BPM31510 acts by targeting the mitochondrial machinery and tumor microenvironment (TME) to create a metabolic shift in cancer cells, leading to cancer cell death.

In addition, BPGbio’s therapeutic pipeline also includes drug candidates for Epidermolysis Bullosa (EB), Squamous Cell Carcinoma (SCC), Sarcopenia, solid and liquid tumors, Huntington’s disease, and Parkinson’s disease. The company’s diagnostic pipeline includes its prostate cancer diagnostic test pstateDx, which is being launched in Mexico, as well as tests being developed and validated for the detection of Parkinson’s disease (ParkinsonDx), pancreatic cancer (PancDx), breast cancer, and liver disease.

Calidi Biotherapeutics To Present New Preclinical Data Highlighting Cell-based Virotherapy (SuperNova) Platform Technology at SITC 2023

On October 10, 2023 Calidi Biotherapeutics, Inc. (NYSE American: CLDI or "Calidi"), a clinical-stage biotechnology company developing a new generation of targeted immunotherapies, reported a poster highlighting new preclinical data and clinical development plans from the company’s novel SuperNova technology will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting in San Diego, CA, taking place November 1-5, 2023.

Presentation Details

Title: A Novel Stem Cell-based Platform for Delivery and Potentiation of Oncolytic Virotherapies
Presenting Authors: Antonio F. Santidrian, PharmD, Ph.D., Chief Scientific Officer, Calidi Biotherapeutics
Boris R. Minev, MD. President, Medical & Scientific Affairs, Calidi Biotherapeutics
Abstract Number: 1419
Date: Friday, November 3, 2023
Time: 9:00 AM – 7:00 PM PDT

Agenus Completes Enrollment in Randomized Phase 2 Clinical Trial of Botensilimab/Balstilimab in Advanced Colorectal Cancer

On October 10, 2023 Agenus Inc. (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers reported completion of the planned patient enrollment in ACTIVATE-Colorectal, a randomized Phase 2 trial in advanced colorectal cancer (CRC) evaluating the efficacy and safety of botensilimab (BOT) as monotherapy and in combination with balstilimab (BAL) or standard of care in patients with metastatic heavily pre-treated colorectal cancer (Press release, Agenus, OCT 10, 2023, View Source [SID1234635837]).

The phase 2 study follows an expanded phase 1 study of over 100 patients with a median of four prior lines of therapy and with 25% having failed previous immunotherapy. At ESMO (Free ESMO Whitepaper) GI earlier this year, data from the phase 1 study were presented. Among the evaluable patients (n=69) who did not have active liver metastases, a confirmed objective response rate of 23% and a median overall survival of 20.9 months were observed.

"There is a significant need for improved treatment options for heavily pre-treated CRC patients and we anticipate data from ACTIVATE-Colorectal will build upon the positive results from our phase 1 study," said Chief Medical Officer, Dr. Steven O’Day. "Our gratitude goes out to the patients, care partners, physicians, and nurses involved in this trial, as we push forward with BOT/BAL to bridge vital gaps in cancer care."

Agenus is exploring global accelerated approval strategies for CRC. The totality of data from the phase 1 and 2 studies will contribute to a planned Biologics License Application to the U.S. FDA in 2024. The U.S. FDA has granted Fast Track designation for BOT/BAL in patients with non-MSI-H/dMMR metastatic colorectal cancer and no active liver involvement who are resistant or intolerant to a fluoropyrimidine, oxaliplatin, and irinotecan, and who have also received a VEGF inhibitor, an EGFR inhibitor and/or a BRAF inhibitor, if indicated.

About Botensilimab

Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and other investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 600 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

Access to Investigational Medicines Policy

Agenus is committed to making our investigational therapies available to patients with cancer based upon advice of a treating physician. Physicians and patients interested in accessing the BOT/BAL combination for CRC should follow the compassionate use policy available on the Agenus website.

MAIA Biotechnology Announces Potent Anticancer Activity of THIO in Gliomas

On October 10, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA), a clinical stage company developing telomere-targeting immunotherapies for cancer, reported that its lead asset THIO showed highly potent anticancer activity in gliomas, an aggressive type of brain tumor that originates from glial cells (Press release, MAIA Biotechnology, OCT 10, 2023, View Source [SID1234635836]). THIO’s novel dual mechanism of action – direct telomere targeting and immune system activation, has previously demonstrated similar efficacy in multiple types of telomerase-active tumors.

THIO was evaluated in various in vitro and in vivo models of gliomas. The results demonstrate the promising therapeutic role of THIO for the treatment of primary and temozolomide-resistant recurrent gliomas through specific telomerase-mediated induction of telomeric DNA damage in glioma cells

"High grade adult gliomas are among the most difficult-to-treat cancers, with less-than-desirable clinical outcomes. These encouraging results further highlight THIO’s excellent anti-cancer activity across several cancer indications," said Vlad Vitoc, M.D., MAIA’s Chief Executive Officer. "We look forward to evaluate THIO as a treatment for brain cancer in clinical setting."

"THIO was effective in the majority of human and mouse glioma cell lines with no apparent toxicity against normal astrocytes. As a monotherapy, THIO demonstrated efficacy in multiple glioma cell lines that had acquired resistance to the current state-of-the art care temozolomide (TMZ). THIO induced apoptosis in several human glioma cell lines that grow as three-dimensional tumor mass-mimicking neurospheres," said MAIA’s Chief Scientific Officer Sergei Gryaznov, Ph.D. "Additionally, THIO produced telomeric DNA damage responses not only in glioma cell lines, but also in diverse human-derived tumor specimens (PDXs). In vivo, THIO significantly decreased tumor proliferation in glioblastoma xenografts and a PDX model of glioblastoma."

The reviewed results were published in: Clin Cancer Res (2021) 27 (24): 6800–6814.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.