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."

On October 10, 2023 Signifying a monumental step forward in the domain of powered antibody therapies, the SparX Group reported its strategic alliance with Arovella Therapeutics Ltd (ASX: ALA) (Press release, Arovella Therapeutics, OCT 10, 2023, View Source [SID1234635831]). This collaboration emphasizes the utilization of SPX-101, an innovative monoclonal antibody (mAb) that targets the Claudin 18.2 (CLDN18.2) tumor specific antigen, as an exciting component in Arovella’s CLDN18.2-CAR-iNKT cells as a leading off-the-shelf CAR-iNKT cell therapy.

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!

Dr. Gui-Dong Zhu, CEO of the SparX Group, elucidated on the significance of this collaboration: "Our partnership with Arovella represents a transformative phase in advancing mAb-based therapies. Invariant Natural Killer T (iNKT) cells, distinguished by their recognition of lipid antigens via the CD1d molecule, have emerged as potent therapeutic vectors. Arovella’s cutting-edge CAR-iNKT platform, encapsulating advanced techniques for in-vitro expansion and post-infusion persistence of iNKT cells, underscores their leadership in this domain. We profoundly acknowledge CLDN 18.2-iNKT cell therapy as a groundbreaking paradigm in oncological therapeutics."

Echoing the enthusiasm, Dr. Michael Baker, CEO of Arovella, remarked, "Licensing the CLDN18.2 mAb sequence from SparX represents a seminal phase in our therapeutic trajectory. SparX’s sophisticated work, spotlighting the unparalleled attributes of their CLDN18.2 monoclonal antibody, coupled with its safety and specificity, accentuates the global attention this molecular target is garnering. We’re uniquely positioned as the only global entity developing a CAR-iNKT cell therapy aimed at CLDN18.2. The synergistic combination of iNKT cells with the CLDN18.2 CAR paves an exciting avenue to develop novel cancer therapeutics."

CLDN18.2 manifests predominantly in gastric cancers (GC), gastroesophageal junction cancers (GEJC), pancreatic cancers (PC), and a spectrum of other solid tumors. Both GC and GEJC represent formidable clinical challenges, registering over a million new cases annually worldwide and culminating in 770,000 fatalities. This places them as the fourth leading cause of cancer-related deaths globally. Spearheaded by SparX, SPX-101 embodies a pinnacle of molecular engineering, stemming from SparX’s sophisticated SAILINGTM discovery platform. This mAb is designed for optimized therapeutic efficacy, offering the potential to be recognized as a best-in-class molecular entity targeting claudin 18.2.

Expounding on the cellular dynamics, Invariant Natural Killer T (iNKT) cells are a specialized T cell subset known for recognizing lipid antigens via the CD1d molecule. These cells possess inherent attributes like tissue infiltration capabilities, counteracting tumor-promoting cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and orchestrating a robust immune response by recruiting auxiliary immune cells against tumor sites. The pathological architecture of tumor development often exposes the CLDN18.2, rendering it accessible to novel treatments such as CAR-iNKT cell therapies. Preliminary clinical findings indicate that iNKT cell therapies might proffer a superior safety profile relative to alternative T cell therapies, notably displaying a reduced propensity for cytokine release syndrome, a prevalent and potential adverse reaction observed in certain cell therapies.