On October 19, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA), a clinical stage company developing telomere-targeting immunotherapies for cancer, reported that preliminary safety and efficacy data from its ongoing Phase 2 clinical trial, THIO-101, was accepted for poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023, being held in Madrid, Spain, October 20-24, 2023 (Press release, MAIA Biotechnology, OCT 19, 2023, View Source [SID1234636159]). THIO-101 is evaluating THIO in patients with advanced Non-Small Cell Lung Cancer (NSCLC) in sequential combination with Regeneron’s anti-PD-1 cemiplimab (Libtayo).

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"We look forward to presenting THIO data at the esteemed ESMO (Free ESMO Whitepaper) Congress, where we will have the opportunity to update global leaders in cancer research from around the world on the only direct telomere targeting agent currently in clinical development," said Vlad Vitoc, M.D., Chairman and Chief Executive Officer of MAIA Biotechnology.

The abstract is available online at the ESMO (Free ESMO Whitepaper) Congress website, and MAIA is scheduled for poster presentation on Monday, October 23. Details of the presentation are as follows:

Abstract title: A Phase 2, Multi-Center, Open-Label, Dose-Optimization Study Evaluating Telomere Targeting Agent THIO Sequenced with Cemiplimab in Patients with Advanced NSCLC – Preliminary Results

Presenter: Tomasz Jankowski, M.D.

Presentation Number: 1493P

Session title: NSCLC, metastatic

About ESMO (Free ESMO Whitepaper) and the ESPO Congress

The European Society for Medical Oncology is the leading professional organization for medical oncology. With more than 30,000 members representing oncology professionals from 168 countries worldwide, ESMO (Free ESMO Whitepaper) is the society of reference for oncology education and information.

The ESMO (Free ESMO Whitepaper) Congress is one of the most influential oncology platforms for clinicians, researchers, patient advocates, journalists and healthcare industry representatives from all over the world. Only the highest quality studies are approved to be presented, supporting dissemination of the latest cutting-edge data, high quality education and unparalleled networking opportunities for oncologists and other stakeholders from all around the world.

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 vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for patients with advanced NSCLC who progressed after first line treatment regimens containing an immune check point inhibitor.

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 Regeneron’s anti-PD-1 cemiplimab (Libtayo) 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 a 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 19, 2023 Adela, Inc., an innovator in blood testing for minimal residual disease monitoring and early cancer detection through a genome-wide methylome approach, reported data demonstrating the feasibility of using its platform for ctDNA quantification and prognostic prediction in head and neck cancer (HNC) and renal cell carcinoma (RCC), at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 Congress (Press release, Adela, OCT 19, 2023, View Source [SID1234636158]). In samples from patients with newly-diagnosed HNC and RCC, collected at Princess Margaret Cancer Centre at University Health Network and the Ontario Tumour Bank, ctDNA was detected and quantified using Adela’s platform, and progression- or recurrence-free survival was compared between samples with high and low ctDNA.

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"To improve patient outcomes by optimizing the treatment delivered, clinicians need additional tools to stratify patients with HNC and RCC based on their likelihood of relapsing," said Geoffrey Liu, MSc, MD, Senior Scientist, Princess Margaret Cancer Centre at University Health Network. "These initial results from the genome-wide methylome platform demonstrating the ability to predict the likelihood of recurrence or progression from samples at diagnosis are promising. Future studies in the post-treatment setting will be needed to confirm these results."

In individuals with newly diagnosed stage I-IV HNC, ctDNA was quantified in 91 biobanked pre-treatment samples with a median follow-up time of 50.6 months. Individuals with higher quantities of ctDNA prior to treatment had a significantly increased likelihood of recurrence or progression [hazard ratio (HR) 5.40 (95% CI 2.25, 12.95), log-rank P<0.001]. A multivariate analysis demonstrated that this higher likelihood of recurrence or progression was independent of cancer stage and clinical characteristics (sex, age, smoking history) [HR 5.24 (95% CI 2.05, 13.42), Wald test P=0.001].

Similarly, in individuals with newly-diagnosed Stage I-IV RCC, ctDNA was quantified in 148 biobanked pre-treatment samples with a median follow-up of 15.7 months. Individuals with higher quantities of ctDNA prior to treatment had a significantly increased chance of recurrence or progression [HR 11.81 (95% CI 4.96, 28.1), log-rank P<0.001]. Worse prognosis persisted in the higher ctDNA group in a sub-population of 89 individuals with Stage I-III RCC [HR 16.26 (95% CI 2.9, 91.15), log−rank P<0.001].

"We are highly encouraged by these results demonstrating the strong prognostic prediction of our tissue-agnostic genome-wide methylome enrichment platform in patients newly diagnosed with cancer," said Anne-Renee Hartman, MD, Chief Medical Officer, Adela. "Our goal is to increase the ease and accessibility of MRD testing for patients and clinicians through a blood test that detects clinically meaningful levels of ctDNA to predict outcomes and inform treatment decisions, without requiring tumor tissue. We are currently evaluating the potential of the platform for assessing prognosis, and monitoring for post-treatment recurrence, in samples from multiple cancer types. We are excited about the potential of our comprehensive methylome approach to be utilized across the cancer continuum."

Presentation Details

Liu, G, MD2, et al. Prognostic Performance of a Genome-Wide Methylome Enrichment Platform in Head and Neck Cancer

Presentation Number: 866P

Date and Time: Sunday October 22nd, 12:00 – 1:00 PM CEST

Session Location: Hall 8

Rini, B. MD 1, et al. Evaluation of a Genome-Wide Methylome Enrichment Platform for Circulating Tumor DNA Quantification and Prognostic Performance in Renal Cell Carcinoma (RCC)

Presentation Number: 1910P

Date and Time: Monday October 23rd, 12:00 – 1:00 PM CEST

Session Location: Hall 8

On October 19, 2023 iOnctura, a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways, reported publication of new research data in the peer-reviewed journal Cancer Research, that supports a strategy of combining autotaxin inhibitor IOA-289 with TGF-β pathway inhibitor IOA-359 (Press release, iOnctura, OCT 19, 2023, View Source;inhibitors-in-cancer-301960883.html [SID1234636157]).

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The research, generated in collaboration with the lab of Professor Davide Melisi, Associate Professor of Medical Oncology at the Department of Medicine, University of Verona, uncovers a central role for autotaxin in resistance to TGF–β pathway inhibition. The TGF-β pathway plays a critical role in promoting tumor aggressiveness, immune escape and resistance to therapy, which has made it an attractive target for cancer therapy. Previous attempts to interrupt TGF-β pathway signaling in cancer have been thwarted by activation of alternative resistance pathways by the tumor. By characterising these resistance mechanisms, iOnctura is designing novel, safe combination treatments that promise to override resistance.

Professor Davide Melisi said: "We have uncovered a new mechanism of action for autotaxin in resistance to TGF–β pathway inhibition. Data generated by our laboratory across in vitro and in vivo models and from human clinical samples support this important finding. These findings pave the way for clinical studies combining autotaxin inhibitors with TGF-β pathway inhibitors, addressing the fibrotic barrier that protects tumors and reversing immunosuppressive mechanisms encouraging the immune system to mount an attack against cancer cells."

Catherine Pickering, Chief Executive Officer of iOnctura, said: "These data support the clinical development of autotaxin inhibitors in combination with TGF-β inhibitors and standard of care for the treatment of pancreatic cancer. This validates our strategy of combining IOA-289, iOnctura’s clinical stage autotaxin inhibitor, with IOA-359, our TGF–β inhibitor that we are preparing for clinical development."

The published research showed that blocking the TGF–β pathway in vivo or in in vitro co-culture models increased the number of autotaxin-producing inflammatory cancer associated fibroblasts (iCAFs). The autotaxin enzyme in turn increased lysophosphatidic acid (LPA) NF- κB signaling in tumor cells which triggered treatment resistance. Specifically, NF-kB promoted CXCL1 expression and recruitment of myeloid suppressive cells (MDSCs), that limited CD8 T-cell infiltration. Adding the autotaxin inhibitor IOA-289 to TGF-β pathway inhibitor galunisertib and standard of care in PDAC-bearing mice, suppressed NF-κB signaling, reduced MDSC and increased CD8 T-cell infiltration, resulting in prolonged overall survival and curing 40% of the mice.

Most importantly, pancreatic ductal adenocarcinoma (PDAC) patients treated with galunisertib from the H9H-MC-JBAJ trial, had significantly elevated levels of autotaxin compared to patients in the control arm. Median progression free survival was shorter for those with higher autotaxin levels compared to those with lower.

On October 19, 2023 Aadi Bioscience, Inc. (NASDAQ: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for patients with mTOR pathway alterations, reported e-poster presentations at the International Gynecologic Cancer Society (IGCS) 2023 Annual Global Meeting, taking place November 5-7, 2023, in Seoul, Korea (Press release, Aadi Bioscience, OCT 19, 2023, View Source [SID1234636156]).

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Abstract and e-poster presentation details are below:

Title: "A phase 2, open-label, single-arm, prospective, multi-center study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer"
Session Title: e-poster
Date/Time: November 5-7, 2023
Authors: Lauren E. Dockery, MD, MS; Anna Priebe, MD; Linda Duska, MD, MPH; Angela K. Green, MD; Cara Mathews, MD; Fernanda Musa, MD; David O’Malley, MD; Allison Puechl, MD; Li Ding, MS, MA; Anita N. Schmid, PhD; Willis H. Navarro, MD; Brian Slomovitz, MD; Kathleen Moore, MD

Abstract highlights:

This is a Phase 2 open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus and letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma, exploring the potential for this combination to produce additive anti-tumor activity in patients with endometrioid-type endometrial carcinoma (EEC)
Dysregulation of mTOR signaling is implicated in the pathology of EEC, in which >80% harbor PTEN or PI3K/AKT/mTOR pathway alterations
Prior clinical studies with mTOR inhibitors and letrozole in endometrial cancer patients have yielded promising results
Alternative treatment options for advanced or recurrent endometrioid-type endometrial carcinoma (EEC) remain necessary despite recent pivotal data demonstrating improved outcomes with immunotherapy plus chemotherapy
In preclinical models, intravenous nab-sirolimus demonstrates significantly higher tumor growth inhibition, intra-tumoral drug accumulation, and greater mTOR target suppression compared with oral inhibitors
An encore presentation titled, "Phase 2, Multicenter, Open-label Basket Trial of nab-Sirolimus for Malignant Solid Tumors Harboring Pathogenic Inactivating Alterations in TSC1 and TSC2 (PRECISION1)" will be displayed as an e-poster during the meeting.

More information can be found on the IGCS meeting website.

On October 19, 2023 Akeso (9926. HK) reported the publication of the phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab (PD-1/CTLA-4 bispecific antibody) in patients with advanced solid tumors in Cell Reports Medicine, a sub-publication of Cell (Press release, Akeso Biopharma, OCT 19, 2023, View Source [SID1234636155]).

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The study findings revealed that cadonilimab reached a dose of 25 mg/kg every 3 weeks (Q3W) without encountering the maximum tolerated dose (MTD). The occurrence of severe immune-related adverse events (irAE) with a grade of 3 or higher was only 6.7%. These results indicate that cadonilimab exhibits a favorable safety and tolerability profile in the treatment of advanced solid tumors. Based on the study, a recommended dose of 6 mg/kg every 2 weeks (Q2W) was established. Remarkably, tumor response was observed in both PD-L1-positive and PD-L1-negative solid tumor populations, indicating that cadonilimab possesses unique efficacy advantages over PD-1/PD-L1 monoclonal antibodies and may have a broader range of potential indications. In conclusion,cadonilimab was found to have a favorable toxicity profile and promising efficacy for patients with solid tumors that were refractory/relapsed to standard therapies or for which no effective standard therapy was available.

Cadonilimab has been approved by the China National Medical Products Administration (NMPA) for recurrent or metastatic cervical cancer. Currently, Akeso has initiated/conducted a series of more than 60 clinical studies globally for patients with solid tumors that were refractory/relapsed to standard therapies or for which no effective standard therapy was available, covering more than 20 types of malignant tumors, including gastric cancer, hepatocellular carcinoma, lung cancer, cervical cancer, pancreatic cancer, renal cancer, esophageal squamous carcinoma, colorectal cancer, nasopharyngeal carcinoma, pleural mesothelioma, and other malignant tumors.

About Cadonilimab(PD-1/CTLA-4 bispecific antibody)
Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy.

Cadonilimab has been approved by the China National Medical Products Administration for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. In its first 12 months on the market, cadonilimab generated impressive sales revenue of 1.15 billion RMB. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer as well as a phase 3 study of cadonilimab in combination with chemotherapy as first-line therapy in gastric cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing. Furthermore, a Phase III study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer.