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]).

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 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.

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.

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!

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.

On October 10, 2023 Toragen Inc., a San Diego-based clinical-stage biotechnology company focused on developing uniquely selective drugs targeting cancers caused by viruses, reported that it has fully enrolled patients in Cohort 1 of its Phase 1 clinical study to evaluate TGN-S11, its first drug candidate, in patients with HPV-associated cancers (Press release, Toragen, OCT 10, 2023, View Source [SID1234635835]).

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!

This Phase 1 trial is an open-label, non-randomized study in cohorts of patients with relapsed, resistant, or metastatic HPV-associated cancers. The study is being conducted in two parts: a dose escalation part and dose expansion part. The dose escalation consists of five Cohorts of three to six patients. The dose expansion will begin in parallel, if Cohorts 1 and 2 of the escalation part are observed to be safe and well-tolerated, and will be one dose level lower than the highest dose observed to be safe and well-tolerated in the dose escalation in combination with a PD-1 checkpoint inhibitor.

"We are delighted to have filled the first Cohort of our Phase 1 trial," said Dr. Neil Clendeninn, Toragen’s Chief Medical Officer. "Once the patients are treated for 28-days with TGN-S11, we intend to begin to enroll Cohort 2. Cohort 1 enrolled quickly, using just one clinical trial site, but we expect recruitment for Cohort 2 to be even more accelerated because we now have three clinical trial sites actively screening patients. Upon successfully completing Cohort 2, we will be able to move to the expansion phase in combination with a PD-1 checkpoint inhibitor."

On October 10, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA), a clinical stage company developing telomere-targeting immunotherapies for cancer, reported that 49 patients have been dosed in MAIA’s Phase 2 clinical trial, THIO-101, evaluating THIO in sequential combination with an immune checkpoint inhibitor (CPI) in patients with advanced Non-Small Cell Lung Cancer (NSCLC) (Press release, MAIA Biotechnology, OCT 10, 2023, View Source [SID1234635834]).

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 feedback received from the clinical trial investigators, the encouraging efficacy observed in dosed patients is prompting physicians to speed up trial enrollment even further. Following U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application, we expect to more than double the number of sites in the near future," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "We are pleased with the pace of enrollment for THIO-101, our go-to-market trial, which is currently exceeding the average enrollment pace in similar NSCLC trials. We look forward to sharing preliminary safety and efficacy data in the coming weeks."

"Out of the 49 patients dosed, 37 already completed at least 1 post baseline assessment, providing key data for our preliminary readings on the safety and efficacy of the treatment with THIO in NSCLC," said Mihail Obrocea, MD, MAIA’s Chief Medical Officer.

THIO is a first-in-class cancer telomere targeting agent administered in sequence with a CPI. The main objectives of the THIO-101 trial are to evaluate the safety, tolerability, and preliminary clinical efficacy of THIO in patients with advanced NSCLC who have experienced disease progression or relapse after initial treatments with an immune CPI alone or in combination with chemotherapy. The trial dosed its first patient in Australia in July 2022 and expanded to include European patients in March 2023.

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.

About THIO-101, Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to an anti-PD-1 agent will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

On October 10, 2023 Cellipont Bioservices, a leading CDMO in cell therapy development and manufacturing and Diakonos Oncology, reported that they have entered into an agreement for the Process Development & cGMP Manufacturing of DOC1021, an autologous dendritic cell vaccine being manufactured for the treatment of glioblastoma multiforme (GBM) and other cancer indications (Press release, Diakonos Oncology, OCT 10, 2023, View Source [SID1234635832]).

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!

Dendritic Cells represent one of the most underutilized cells in Immunotherapy. With a first of its kind approach, Diakonos’ DOC1021 activates a natural anti-viral immune response against a patient’s tumor. Due to the promising results in both safety and efficacy in its phase 1 trial, Diakonos recently received Fast Track designation by the FDA.

Glioblastoma is the most common and deadliest type of primary brain tumor in adults. It originates in the brain’s glial cells, which are supportive cells that surround and protect nerve cells. Despite considerable research and development, the current 7% five-year survival rate has seen limited improvement.

"We are deeply honored to have been chosen as Diakonos’ partner in this critical endeavor," stated Darren Head, Chairman of the Board of Cellipont Bioservices. "With our extensive expertise in cell therapy development and manufacturing, coupled with our purpose-built Woodlands facility, we are confident that our collaboration will pave the way for bringing this life-saving therapy to countless glioblastoma patients."

"As DOC1021 is personalized to each patient, it was critical to find a CDMO partner that could not only help commercialize this incredibly promising treatment but exceed our quality standards for each and every patient," said Mike Wicks, Chief Executive Office of Diakonos. "We could not be happier to find that partner in Cellipont, and we look forward to changing patient outcomes in GBM as well as other cancer indications."