On March 20, 2025 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported the publication of preclinical data for its lead proprietary telomere-targeting THIO dimer in the peer-reviewed scientific journal Naunyn-Schmiedeberg’s Archives of Pharmacology (Press release, MAIA Biotechnology, MAR 20, 2025, View Source [SID1234651332]).

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In a preclinical study, THIO and its new described dimer form were found to be potent inhibitors of Glutathione S-transferase Pi (GSTP1), a key enzyme implicated in cancer progression and chemoresistance and a highly important factor for the detoxification of cancer cells. The findings suggest that the dimerized form of THIO could enhance chemotherapeutic efficacy by effectively targeting GSTP1 and reducing drug resistance. The article, titled "Investigation of the inhibitory effects of the telomere-targeted compounds on glutathione S-transferase P1," was published on February 15, 2025.

"The esteemed Archives of Pharmacology has published our first peer-reviewed paper about the unique potential of the lead molecule in our second-generation THIO program," said Vlad Vitoc, M.D., CEO of MAIA. "Preclinical findings illuminate the superior GSTP1 binding affinity and inhibitory potency of this novel prodrug and support continued development of this new strategy for cancer therapy."

MAIA’s second generation research and discovery platform seeks to identify new telomere-targeting THIO-like compounds with potentially improved specificity towards cancer cells relative to normal cells and with potentially increased anticancer activity. More than 80 THIO-like compounds have been developed as part of the second-generation telomere targeting program.

"Our manuscript highlights the potential of THIO’s dimer as a potent GSTP1 inhibitor and a promising new strategy for enhancing cancer treatment and overcoming drug resistance," said Chief Scientific Officer Sergei Gryaznov, Ph.D. "Further exploration of the combinatorial effects of THIO with standard chemotherapeutic agents could provide valuable insights for optimizing standard cancer treatment protocols. These efforts could pave the way for novel, targeted strategies in cancer therapy, offering new hope in the fight against drug-resistant cancers."

About Naunyn–Schmiedeberg’s Archives of Pharmacology

Naunyn–Schmiedeberg’s Archives of Pharmacology, founded in 1873, is the oldest existing pharmacological journal and a dedicated platform for new and significant information on drug action and toxicity of chemical compounds. The peer-reviewed scientific journal covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in neuropharmacology and cardiovascular pharmacology and those describing drug actions at the cellular, biochemical and molecular levels.

About Ateganosine

Ateganosine (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 induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. Ateganosine-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with ateganosine 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. Ateganosine 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 March 20, 2025 Wugen, Inc., a clinical-stage U.S. biotechnology company developing allogeneic, off-the-shelf cell therapies for the treatment of hematological and solid tumor malignancies, reported the dosing of the first patients in its pivotal Phase 2 study evaluating WU-CART-007, a potential first-in-class, investigational, anti-CD7 CAR-T cell therapy for pediatric and adult patients with relapsed or refractory (R/R) T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma (T-ALL/LBL) (Press release, Wugen, MAR 20, 2025, View Source [SID1234651317]).

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"The data we have previously reported from our Phase 1/2 study on the WU-CART-007 program has paved the way for the initiation of this pivotal study, and suggests it has the potential to set a new standard of care for relapsed or refractory T-ALL/LBL," said Kumar Srinivasan, Ph.D., M.B.A., president and chief executive officer of Wugen. "The program has earned multiple U.S. Food and Drug Administration accelerated approval pathway designations, including RMAT, Fast Track, Orphan Drug, and Rare Pediatric Disease, as well as Priority Medicines designation in the EU. With this pivotal study now underway, we are advancing toward a much-needed off-the-shelf CAR-T option for patients who face historically poor outcomes and limited treatment alternatives."

Wugen previously announced positive results from a Phase 1/2 cohort expansion study showing clinically manageable safety and evidence of anti-leukemic activity (overall response rate of 91%; composite complete remission rate of 73%) in heavily pretreated patients with R/R T-ALL/LBL. Results were presented at both the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) in December of 2024 and the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress in June of 2024.

"It’s been 20 years since a new medicine was approved for patients with relapsed or refractory T-ALL/LBL, which remain challenging hematologic malignancies with limited treatment options in the relapsed or refractory setting," said Cherry Thomas, M.D., chief medical officer of Wugen. "WU-CART-007 has shown clinical response and manageable safety, making it a promising off-the-shelf cell therapy candidate to fill a longstanding treatment gap. The enthusiasm around the program and the need for new treatments have been reflected in the study recruitment thus far, as it is enrolling faster than anticipated."

Pivotal Study Design

The pivotal study entitled, "A Phase 2 Study of WU-CART-007, an Anti-CD7 Allogeneic CAR-T Cell Therapy in Patients with Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma", (T-RRex) is a single arm trial evaluating the efficacy and safety of WU-CART-007 in patients with R/R T-ALL/LBL and T-ALL/LBL. The study will involve two groups: a R/R cohort and subsequently an exploratory minimal residual disease (MRD)-positive cohort.

About WU-CART-007

WU-CART-007 is an allogeneic, off-the-shelf, fratricide-resistant CD7-targeted CAR-T cell therapy engineered to overcome the technological challenges of harnessing CAR-T cells to treat CD7+ hematological malignancies. Wugen is deploying CRISPR/Cas9 gene editing technology to delete CD7 and the T cell receptor alpha constant (TRAC), preventing CAR-T cell fratricide and mitigating the risk of graft-versus-host-disease (GvHD). WU-CART-007 is manufactured using healthy donor-derived T cells to eliminate the risk of malignant cell contamination historically observed in the autologous CAR-T setting. WU-CART-007 is currently being evaluated in a global Phase 1/2 clinical trial for the treatment of relapsed or refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). More information on the Phase 1/2 trial is available on clinicaltrials.gov, identifier NCT# 04984356 and on the Phase 2 pivotal trial on clinicaltrials.gov, identifier NCT06514794.

WU-CART-007 has received Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration and Priority Medicines (PRIME) Scheme designation in the European Union for the treatment of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphoblastic lymphoma (T-LBL). RMAT and PRIME designations provide increased agency support to expedite the development and review of promising therapies for patients in need.

On March 20, 2025 BPGbio, Inc., a leading biology-first, AI-powered, clinical stage biopharma focused on mitochondrial biology and protein homeostasis, reported its participation in the 5th Annual TPD and Induced Proximity Summit, taking place March 25-27, 2025, in London, UK (Press release, BPGbio, MAR 20, 2025, View Source [SID1234651333]). BPGbio executive Vivek K. Vishnudas, Ph.D., Chief Technology Officer and R&D Site Head, will present a session titled "Pioneering a Differentiated Approach to Targeted Protein Degradation Using the Ubiquitin Conjugating Enzyme (E2) Family." Dr. Vishnudas will speak on March 26 as part of the conference’s Pre-Clinical and Translation track, highlighting the latest advancements in BPGbio’s protein homeostasis program and the potential of E2-based therapeutics in oncology and neurology.

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"Our innovative approach to targeted protein degradation via the ubiquitin-conjugating enzyme (E2) family represents a breakthrough in drug development, allowing us to address previously undruggable targets and overcome resistance mechanisms inherent in traditional E3-based strategies," said Dr. Vishnudas. "We look forward to sharing our progress in developing E2-based bifunctional and glue degraders for oncology and neurodegenerative disorders."

In addition to its E2-focused approach, BPGbio’s protein homeostasis program incorporates a proprietary library of over 1,000 Ro3 fragments identified as potential ligands and seed compounds for E2 targets. The program also features proprietary ternary structures, a computational toolkit for E2 ligand design, and advanced assays designed to optimize selectivity and specificity.

BPGbio’s therapeutic pipeline includes drug candidates for glioblastoma (orphan drug), pancreatic cancer (orphan drug), primary CoQ10 deficiency (rare pediatric disease designated), epidermolysis bullosa (EB, orphan drug), squamous cell carcinoma (SCC, orphan drug), sarcopenia, solid and liquid tumors, Huntington’s disease (orphan drug), and Parkinson’s disease. The company’s diagnostic pipeline includes its prostate diagnostic test (pstateDx), as well as tests in development for the detection of Parkinson’s disease (parkinsonDx), pancreatic cancer (pancDx), breast cancer, and liver disease.

On March 20, 2025 Amphista Therapeutics, a leader in the discovery of next-generation, Targeted Protein Degradation (TPD) medicines, reported the presentation of the discovery of a novel mechanism for BRD9 degradation, differentiated from cereblon- or VHL-based PROTACs using the Company’s novel Targeted Glue technology (Press release, Amphista Therapeutics, MAR 20, 2025, View Source [SID1234651318]). These will be at the 2nd SMR Molecular Glues meeting being held on 21 March in Stevenage, UK, and the 5th Annual TPD and Induced Proximity Summit Europe being held 25-27 March in London, UK.

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Dr. Marta Carrara, Associate Director Target Discovery & Validation at Amphista, will deliver the oral presentations that describe the generation of selective and potent degraders of BRD9, an emerging target in acute myeloid leukemia. Amphista’s proprietary Targeted Glue catalyzes degradation via DCAF16, a relatively uncharacterised E3 ligase, and therefore has the potential to create novel TPD therapeutics for application across a wide range of indications.

These data illustrate the strength of the Company’s proprietary chemistry and its Eclipsys platform in enabling the rational design of orally bioavailable protein degraders.

Details of presentations:
Conference: 2nd SMR Molecular Glues meeting, Stevenage, UK
Presentation Date and Time: Friday 21st March, 11.50am-12.30pm GMT
Presentation Title: Degradation of BRD9 by a novel "Targeted Glue"

Conference: 5th Annual TPD and Induced Proximity Summit Europe, London, UK
Presentation Date and Time: Wednesday 26th March, 9.00am GMT
Presentation Title: Rational design of a novel DCAF16-recruting BRD9 Targeted Glue

On March 20, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company, reported a peer-reviewed publication highlighting a potentially significant breakthrough in addressing drug resistance to EGFR-targeted therapies for non-small cell lung cancer (NSCLC) patients (Press release, Kairos Pharma, MAR 20, 2025, View Source [SID1234651334]). Recent findings published in Drug Resistance Updates highlight the critical role of CD105 (endoglin) in mediating resistance to osimertinib, a frontline treatment for EGFR-mutant NSCLC. The study, titled, "CD105 blockade restores osimertinib sensitivity in drug-resistant EGFR-mutant non-small cell lung cancer," demonstrated that CD105 expression is upregulated as a mechanism of therapy resistance, correlating with poor prognosis in patients.

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"We believe our latest findings represent a paradigm shift in overcoming resistance to EGFR-targeted therapies in NSCLC," said Neil Bhowmick, Ph.D., Kairos Pharma Chief Scientific Officer. "Revealing this mechanism-of-action underscores our commitment to advancing precision oncology and bringing innovative therapies to patients in need."

In preclinical models, targeting CD105 with ENV105 (carotuximab), a CD105-neutralizing antibody successfully restored treatment sensitivity to EGFR-targeted therapies. Notably, combining osimertinib with ENV105 reinstated susceptibility to EGFR inhibition through metabolic reprogramming and enhanced chromatin accessibility. These findings confirm the efficacy of this novel combination therapy strategy in overcoming drug resistance in this model of non-small cell lung cancer.

Dr. John Yu, CEO, stated, "These findings in lung cancer corroborate data in prostate cancer, breast cancer and colon cancer, that point to CD105 being a central mechanism of cancer drug resistance. We believe ENV105 can reverse this resistance in cancer models, and our clinical trials are designed to definitively demonstrate its potential impact."

The global NSCLC treatment market is projected to reach $45 billion by 2030, driven by advancements in targeted therapies. However, drug resistance remains a major challenge. The ability of ENV105 to enhance EGFR-targeted therapy effectiveness positions it as a high-value asset in next-generation oncology treatment. Kairos Pharma is currently evaluating this transformative cancer therapy in ongoing clinical trials for EGFR-driven lung cancer patients. The study can be accessed here.