On October 23, 2023 Galecto, Inc. (NASDAQ: GLTO), a clinical-stage biotechnology company focused on the development of novel treatments for fibrosis and cancer, reported a poster with new and encouraging clinical data, including two additional partial responders, from the dose-finding Part A of its Phase 1b/2a trial (NCT05240131) (the GALLANT-1 trial) at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain (Press release, Galecto Biotech, OCT 23, 2023, View Source [SID1234636244]). The GALLANT-1 trial is designed to study the combination of atezolizumab (Tecentriq) and GB1211, Galecto’s first-in-class, oral small-molecule galectin-3 inhibitor candidate, in the first-line treatment of patients with metastatic/advanced non-small cell lung cancer (NSCLC).

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At the recommended Phase 2 dose level of 100 mg GB1211 twice daily, investigator-assessed objective tumor responses (defined as partial responses per RECIST criteria 1.1) were observed in three of five patients (60%) who received GB1211 for at least three weeks. Response rates of only 22–38% have been observed with atezolizumab monotherapy in the first-line treatment of advanced NSCLC, suggesting a potential benefit of adding GB1211 to atezolizumab. The Company believes that GALLANT-1 is the first clinical trial to show that combining an oral galectin-3 inhibitor with a checkpoint inhibitor may enhance the effect of checkpoint inhibitors.

In addition, insights from early biomarker analyses revealed a trend showing that responders had increased levels of galectin-3 at baseline, and stable or decreasing galectin-3 levels during treatment. In contrast, patients with progressive disease demonstrated increasing levels of galectin-3 during treatment. This correlation suggests that the detection of galectin-3 levels could potentially be used to select and monitor patient populations.

Overall, the combination of GB1211 100 mg and atezolizumab appeared to be well-tolerated, with predominantly Grade 1 and Grade 2 treatment emergent adverse effects observed. At the 200 mg twice daily dose-level, two severe dose-limiting skin reactions were observed that may indicate lymphocyte activation in line with the GB1211 mode of action, which resulted in a reduction to the 100 mg GB1211 dose level. Importantly, these skin rashes were not observed at the recommended Phase 2 dose level of 100 mg GB1211 twice daily.

As part of Galecto’s recently announced strategic alternative process, Galecto has determined that it will not initiate Part B of the GALLANT-1 trial and will instead reallocate its resources to focus on the treatment of severe liver diseases. Galecto will continue to supply GB1211 100 mg for the upcoming investigator-initiated Phase 2 trial at Providence Portland Medical Center’s Earle A. Chiles Research Institute (EACRI). This trial, which is expected to be initiated in early 2024, will evaluate the safety and efficacy of GB1211 in combination with pembrolizumab (Keytruda). Galecto plans to explore external options for partnering and/or funding additional oncology-focused activities for GB1211 as part of its strategic alternative process.

Following the poster presentation at the ESMO (Free ESMO Whitepaper) Congress, the poster will be available on the Scientific Conferences page of Galecto’s investor relations website at View Source

About GB1211 and Galectin-3 Mechanisms in Cancer

Increased galectin-3 expression in tumors is linked to tumor growth, invasiveness and metastatic potential. In the tumor tissue, galectin-3 supports the creation of fibrosis, tumor proliferation, metastasis, and immune avoidance. Galectin-3 uses a host of mechanisms to increase tumor growth and metastasis. Furthermore, increased levels of galectin-3 in the tumor microenvironment facilitates tumor escape from the immune response by suppressing essential T-cell functions and activating tumor-protecting macrophages.

Evidence suggests that galectin-3 can enhance PD-1 and PD-L1 binding and avert the interference of anti-PD-1/anti-PD-L1 therapies by blocking the binding of the antibodies to their respective targets. GB1211 is designed to counter these effects.

About the GALLANT-1 trial

The Phase 1b/2a trial of GB1211 in combination with atezolizumab (Tecentriq) was designed to be a randomized, double-blind, placebo-controlled trial in patients with NSCLC in the first-line setting. Part A of the GALLANT-1 trial was an open-label trial that determined the 100 mg dose of GB1211 to be the recommended dose in future oncology trials. Part B of the GALLANT-1 trial had been designed to evaluate safety and tumor shrinkage in NSCLC patients and explore tumor response rate based on RECIST criteria (version 1.1), clinical activity, and immune biomarkers.

On October 23, 2023 FibroGen, Inc. (NASDAQ: FGEN) reported that it will announce third quarter 2023 financial results on Monday, November 6 after the market close (Press release, FibroGen, OCT 23, 2023, View Source [SID1234636243]). FibroGen will also conduct a conference call on that day at 5:00 PM Eastern Time with the investment community to further detail the company’s corporate and financial performance.

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Conference Call and Audio Webcast
Interested parties may access a live audio webcast of the conference call via the "Investor Relations" page of the Company’s website at www.fibrogen.com. To access the call by phone, please go to this link (registration link), and you will be provided with dial-in details. To avoid delays, we encourage participants to dial in to the conference call fifteen minutes ahead of the scheduled start time. A replay of the webcast will also be available for a limited time at the following link (webcast replay).

On October 23, 2023 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for solid and liquid malignancies and inflammatory diseases based on its unique Mimicry platform, reported updated, encouraging results from Phase 1/2 SPENCER trial of EO2401 in combination with nivolumab in adrenocortical carcinoma (ACC) and metastatic pheochromocytoma/paraganglioma (MPP), two forms of adrenal tumors (Press release, Enterome, OCT 23, 2023, View Source [SID1234636242]). EO2401 is composed of three non-self, microbiome-derived HLA-A2 restricted peptides, designed to activate memory CD8 T cells targeting tumor-associated antigens (TAAs) upregulated in adrenal tumors.

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The data was featured in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023. The presentation entitled, "EO2401 (E) peptide immunotherapy + nivolumab (N) in adrenocortical carcinoma (ACC) and metastatic pheochromocytoma/paraganglioma (MPP); EOADR1-19/SPENCER" was delivered by Prof. Eric Baudin, Head of the Endocrine Oncology Unit at Gustave-Roussy, Villejuif, France.

"We are excited to share positive, updated results from the SPENCER trial at this year’s ESMO (Free ESMO Whitepaper) Congress," said Pierre Belichard, Chief Executive Officer of Enterome. "EO2401 in combination with nivolumab continues to demonstrate a meaningful anti-tumor activity in patients with adrenal tumors. The combination was well-tolerated and generated durable immune responses."

Dr. Eric Baudin, Associate Professor and Head of the Endocrine Oncology Unit at Gustave-Roussy, commented: "The results presented at ESMO (Free ESMO Whitepaper) are very encouraging. The data represents a clinical validation of EO2401 as demonstrated by the correlation between the strength of immune response and degree of tumor shrinkage on CT scans, a direct measure of tumor activity".

Conclusion as presented at the ESMO (Free ESMO Whitepaper) conference:

EO2401 in combination with nivolumab was generally well tolerated in patients with advanced/metastatic adrenal tumors
Encouraging results in pretreated patients with ACC; median duration of disease control of 9 months, and 3 of 26 patients stopped study treatment at 2 years only due to protocol
Longer follow-up needed to interpret results in pheochromocytoma/paraganglioma patients
EO2401 in combination with nivolumab achieved long term stabilizations of "cold tumors" (TMB-low, MSS, PDL1-low adrenal tumors; ACC and MPP)
Specific CD8 T cell immune responses could be a biomarker
About SPENCER

SPENCER (EOADR1-19) is a multicenter, open-label, first-in-human, Phase 1/2 study of EO2401 in combination with an immune checkpoint inhibitor (nivolumab) for the treatment of patients with locally advanced or metastatic adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma. The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of the combination in sites in Europe and the US.

For more information on the Phase 1/2 trial of EO2401 in adrenocortical carcinoma, please visit ClinicalTrials.gov Identifier: NCT04187404

About EO2401

EO2401 is Enterome’s first-in-class off-the-shelf OncoMimics peptide-based immunotherapy. It combines three microbial-derived OncoMimics peptides that closely mimic specific cytotoxic T cell (CD8+ T cell) epitopes on the Tumor-Associated Antigens IL13Ra2, BIRC5, and FOXM1, combined with the helper peptide (CD4+ T cell epitope) Universal Cancer Peptide 2 (UCP2).

About OncoMimics

OncoMimics immunotherapies are designed to activate pre-existing effector memory T cells that target bacterial (non-self) peptides, which are strongly cross-reactive against selected Tumor-Associated Antigens (TAAs), or B cell markers expressed on tumoral cells, resulting in a rapid, targeted cytotoxic response against cancer.

On October 23, 2023 Circle Pharma, in collaboration with the laboratory of Violeta Serra, Ph.D., at Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain, reported preclinical data demonstrating the efficacy of Circle’s oral Cyclin A/B inhibitor macrocycles in patient-derived breast cancer tumor models (Press release, Circle Pharma, OCT 23, 2023, View Source [SID1234636241]). This significant development was presented at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).

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The study in 40 breast cancer cell lines identified an association between hallmark pathway scores in E2F, G2/M, and mitotic spindle pathways and sensitivity to Cyclin A/B inhibition. Most notably, multiple triple-negative breast cancer (TNBC) cell lines and luminal B breast cancer cell lines displayed sensitivity to Cyclin A/B inhibition. These findings were instrumental in selecting TNBC and luminal breast cancer patient-derived tumor models for subsequent in vivo efficacy studies. In these in vivo studies, oral administration of Circle’s Cyclin A/B inhibitor led to substantial tumor regression in both TNBC and luminal breast cancer models, with complete response observed in a luminal B breast cancer model derived from a patient whose tumor had previously progressed following multiple treatments, including with a CDK4/6 inhibitor.

Breast cancer is the second leading cause of cancer-related deaths in women globally. Triple negative breast cancer, which accounts for 10-20% of all breast cancer cases, is an aggressive and challenging subtype of breast cancer, associated with poor prognosis and high risk of relapse1. Because TNBC lacks specific receptors (estrogen, progesterone, or HER2) that some other breast cancers have, many newer therapies used to target these receptors in other forms of breast cancer are not effective. Luminal breast cancers are hormone receptor-positive and generally less aggressive than TNBC. Luminal breast cancers can be further divided into two subtypes: luminal A (HR+/ER+/HER2+) and luminal B (HR+/PR+/HER2-). These two subtypes make up about 70% of all breast cancer cases2.

Dr. Serra expressed optimism about the results, stating, "The responses in both TNBC and luminal breast cancer models are very compelling, and we look forward to evaluating the effects of these first-in-class Cyclin A/B inhibitors in additional models in future studies."

"October is breast cancer awareness month; at Circle our mission is to bring new therapies and new hope to patients who have limited treatment options, and this new research indicates that we may have an opportunity to do just that for patients with breast cancer. We will work assiduously to bring this first-in-class therapy to patients," said David J. Earp, JD, PhD, Circle Pharma’s chief executive officer.

Building on the success demonstrated in small cell lung cancer and ovarian cancer models, Circle Pharma plans to file an investigational new drug (IND) application for its Cyclin A/B inhibitor clinical candidate, CID-078, with the U.S. Food and Drug Administration (FDA) and initiate clinical development in 2024.

ABOUT CIRCLE PHARMA’S CYCLIN A/B INHIBITOR PROGRAM
Circle Pharma has developed an orally bioavailable macrocycle with dual cyclin A and B inhibitory activity that drives synthetic lethality in multiple tumor types. In biochemical and cellular studies, Circle’s Cyclin A/B inhibitor has been shown to potently and selectively disrupt the protein-protein interaction between Cyclins A and B and their key substrates, including E2F (a substrate of Cyclin A) and Myt1 (a substrate of Cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B inhibitors to cause pronounced tumor regression in multiple xenograft models. Circle Pharma plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for its clinical candidate, CID-078, and initiate clinical development in 2024.

On October 23, 2023 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported follow-up data from its ongoing first-in-human Phase 1/2 trial (NCT04503278; 2019-004323-20) evaluating the safety and efficacy of the Company’s Claudin-6 (CLDN6)-directed CAR-T cell therapy candidate BNT211 in patients with CLDN6-positive refractory/relapsed solid tumors (Press release, BioNTech, OCT 23, 2023, View Source [SID1234636239]). The data show encouraging signs of clinical activity and an increased persistence of cancer-specific CAR-T cells when combined with CARVac. At the ESMO (Free ESMO Whitepaper) Congress 2023 in Madrid, Prof. John Haanen, M.D., Ph.D., Netherlands Cancer Institute (NKI), Amsterdam, Netherlands presented the data in an oral late-breaking data session which confirms the positive interim data presented at this year’s American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, USA.

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"Our goal is to unlock the potential of CAR-T for solid tumors and to help improve the outcomes for a broad range of hard-to-treat tumors," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "BNT211 aims to address two of the key limitations of CAR-T cell approaches in solid tumors, namely the lack of suitable cancer-specific cell surface targets and the limited persistence of CAR-T cells. To address this challenge, we have designed a CLDN6-specific autologous CAR-T cell therapy that we combine with our mRNA-based vaccine CARVac."

The data update included 44 patients who received CLDN6 CAR-T cells at four dose levels alone or in combination with CARVac. Patients with germ cell tumors (n=16), ovarian cancer (n=17) and other solid tumor types (n=11) were treated. In course of the dose escalation, a dose-dependent increase in adverse events was observed, with cytokine release syndromes occurring in 23 of 44 safety evaluable patients. In most cases, these were of grade 1 and 2, with one patient with a grade 3 and one with a grade 4 event. Neurotoxicity was mild and self-limiting in two patients. Of the total 44 patients, 38 were efficacy evaluable. The overall response rate ("ORR") for these 38 patients was 45% and the disease control rate ("DCR") 74%. Further, 27 patients were treated with CLDN6 CAR-T cells at dose level 2 (1×108 CAR-T cells) with or without CARVac. At this dose level, 13 patients showed partial responses resulting in an ORR of 59% and a DCR of 95%. Additionally, in the same cohort, patients who received CARVac showed a prolonged persistence of CAR-T cells.

These results further underline the potential of BioNTech’s BNT211 program. One objective of the ongoing Phase 1/2 trial is to determine the recommended dose for the initiation of a potential pivotal Phase 2 trial in patients with germ cell tumors which is expected to be initiated in 2024.

About BNT211
To harness the power of cell therapies for solid cancers, BioNTech has combined their CAR-T and FixVac platform technologies to develop a tumor-specific CAR-T cell therapy which is enhanced by a CAR-T Cell Amplifying RNA Vaccine (CARVac) that is based on BioNTech’s mRNA-lipoplex technology and encodes for the CAR-T target antigen. The mRNA vaccine is designed to boost CAR-T persistence and functionality. BNT211 is a CAR-T cell therapy directed against the novel oncofetal antigen Claudin-6 (CLDN6), a target expressed on multiple solid tumors such as ovarian cancer, sarcoma, testicular cancer, endometrial cancer and gastric cancer. The program is currently being evaluated in a first-in-human Phase 1/2 trial as a monotherapy and in combination with a CLDN6-encoding CARVac in patients with CLDN6-positive relapsed or refractory advanced solid tumors.