On July 28, 2025 Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing development of targeted therapies for oncology, reported positive topline results from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 clinical trial evaluating gedatolisib plus fulvestrant with and without palbociclib versus fulvestrant in adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA wild-type, locally advanced or metastatic breast cancer, following progression on, or after, treatment with a CDK4/6 inhibitor and an aromatase inhibitor (Press release, Celcuity, JUL 28, 2025, View Source [SID1234654569]).

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In the trial, the gedatolisib triplet demonstrated a statistically significant and clinically meaningful improvement in PFS among patients, reducing the risk of disease progression or death by 76% compared to fulvestrant (based on a hazard ratio [HR] of 0.24, 95% confidence interval [CI] 0.17-0.35; p<0.0001). The mPFS, as assessed by blinded independent central review ("BICR"), was 9.3 months with the gedatolisib triplet versus 2.0 months with fulvestrant, an incremental improvement of 7.3 months.

The gedatolisib doublet also demonstrated a statistically significant and clinically meaningful improvement in PFS among patients, reducing the risk of disease progression or death by 67% compared to fulvestrant (HR of 0.33, 95% CI 0.24-0.48; p<0.0001). The mPFS, as assessed by BICR, was 7.4 months with the gedatolisib doublet versus 2.0 months with fulvestrant, an incremental improvement of 5.4 months.

The topline efficacy data from the VIKTORIA-1 PIK3CA wild-type cohort established several new milestones in the history of drug development for HR+/HER2- advanced breast cancer:

· The hazard ratios for the gedatolisib triplet and doublet are more favorable than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC.

· The 7.3- and 5.4-months incremental improvements in median PFS for the gedatolisib triplet and gedatolisib doublet over fulvestrant, respectively, are higher than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC receiving at least their second line of therapy.

· Gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR pathway to demonstrate positive Phase 3 results in patients with HR+/HER2-/PIK3CA wild-type ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor.

Sara Hurvitz, MD, Senior Vice President, Clinical Research Division, Fred Hutchinson Cancer Center, Professor and Head, Division of Hematology and Oncology, University of Washington, Department of Medicine and co-principal investigator for the trial said: "Patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease has progressed while on, or after, treatment with a CDK4/6 inhibitor typically derive limited benefit from subsequent endocrine-based therapy. The topline data for both gedatolisib regimens from VIKTORIA-1 are potentially practice-changing. To my knowledge, we have not seen Phase 3 results in patients with HR-positive, HER2-negative advanced breast cancer before where there was a quadrupling of the likelihood of survival without disease progression relative to the study control."

Treatment discontinuation due to a treatment-related adverse event for the gedatolisib triplet and gedatolisib doublet was lower than was observed in Arm D of the Phase 1b trial in patients with ABC, and lower than observed in any Phase 3 trials for currently approved drug combinations in HR+/HER2- ABC. Additionally, the gedatolisib triplet and gedatolisib doublet were better tolerated than was observed in the Phase 1b trial in patients with ABC, including lower rates of hyperglycemia and stomatitis.

Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity said: "The topline data from VIKTORIA-1 demonstrate the potential for gedatolisib to become a transformative new medicine for the treatment of patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with CDK4/6 inhibitors. The 7.3 and 5.4-months incremental improvement in median PFS relative to fulvestrant for the gedatolisib regimens are potentially paradigm shifting results. We are also very excited that treatment with gedatolisib combined with fulvestrant with or without palbociclib was well-tolerated by the VIKTORIA-1 patients and that only a few patients discontinued treatment due to an adverse event."

Brian Sullivan, Chairman, Chief Executive Officer and co-founder of Celcuity said, "The efficacy improvement relative to the control that each of the gedatolisib regimens demonstrated was historic for this patient population. We are excited about the potential opportunity to provide a breakthrough therapeutic option for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer."

Full data from the PIK3CA wild-type cohort of the VIKTORIA-1 clinical trial will be presented at an upcoming medical conference later this year. Celcuity expects to submit a New Drug Application for gedatolisib to the U.S. Food and Drug Administration in the fourth quarter of 2025. Topline data for the VIKTORIA-1 PIK3CA mutation cohort is expected by the end of 2025.

Webcast and Conference Call Information

The Celcuity management team will host a webcast/conference call on Monday, July 28, 2025, at 8:00 a.m. ET to discuss the topline results from the Phase 3 VIKTORIA-1 trial. Those who would like to participate may access the live webcast here, or register in advance for the teleconference here. A replay of the webcast will be available on the Celcuity website following the live event.

Notes

HR+/HER2- Breast cancer

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed globally in 2022.1 While survival rates are high for those diagnosed with early breast cancer, only approximately 30% of patients who are diagnosed with or who progress to metastatic disease are expected to live five years after their diagnosis.2 HR+/HER2- breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all breast cancers.2

Three interconnected signaling pathways, estrogen, cyclin D1-CDK4/6, and PI3K/AKT/mTOR (PAM), are primary oncogenic drivers of HR+, HER2- breast cancer.3 Therapies inhibiting these pathways are approved and used in various combinations for advanced breast cancer. Currently approved inhibitors of the PAM pathway for breast cancer target a single PAM pathway component, such as PI3Kα, AKT, or mTORC1.4,5,6,7 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.8 Survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.2 Optimizing the inhibition of the PAM pathway is an active area of focus for breast cancer research.

VIKTORIA-1

VIKTORIA-1 is a Phase 3 open-label, randomized clinical trial to evaluate the efficacy and safety of gedatolisib in combination with fulvestrant with or without palbociclib in adults with HR+/HER2- ABC whose disease progressed on or after prior CDK4/6 therapy in combination with an aromatase inhibitor. The clinical trial is enrolling subjects regardless of PIK3CA status while enabling separate evaluation of subjects according to their PIK3CA status. Subjects who meet eligibility criteria and do not have confirmed PI3KCA mutations (WT) were randomly assigned (1:1:1) to receive a regimen of either gedatolisib, palbociclib, and fulvestrant, gedatolisib and fulvestrant, or fulvestrant. Subjects who meet eligibility criteria and have confirmed PI3KCA mutations (MT) are randomly assigned (3:3:1) to receive a regimen of either the gedatolisib triplet, alpelisib and fulvestrant, or the gedatolisib doublet.

Gedatolisib

Gedatolisib is an investigational, multi-target PAM inhibitor that potently targets all four class I PI3K isoforms, mTORC1, and mTORC2 to induce comprehensive blockade of the PAM pathway.9,10,11 As a multi-target PAM inhibitor, gedatolisib’s mechanism of action is highly differentiated from currently approved single-target inhibitors of the PAM pathway.11 Inhibition of only a single PAM component gives tumors an escape mechanism through cross-activation of the uninhibited targets. Gedatolisib’s comprehensive PAM pathway inhibition ensures full suppression of PAM activity by eliminating adaptive resistance cross-activation that occurs with single-target inhibitors. Unlike single-target inhibitors of the PAM pathway, gedatolisib has demonstrated equal potency and comparable cytotoxicity in PIK3CA-mutant and -wild-type breast tumor cells in nonclinical studies and early clinical data.

On July 28, 2025 MAIA Biotechnology, Inc. (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company focused on developing targeted immunotherapies for cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for ateganosine (THIO, 6-thio-dG or 6-thio-2’-deoxyguanosine) for the treatment of non-small cell lung cancer (NSCLC) (Press release, MAIA Biotechnology, JUL 28, 2025, View Source [SID1234654586]). Ateganosine is currently being evaluated in a pivotal Phase 2 THIO-101 clinical trial evaluating its anti-tumor activity when followed by a checkpoint inhibitor.

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Ateganosine is a first-in-class small molecule that compromises telomere structure and function in cancer cells, leading to rapid tumor cell elimination and specific immune memory. Through telomerase-mediated action, ateganosine reverses intrinsic or acquired resistance to immune checkpoint inhibitors (ICIs).

"FDA’s Fast Track Designation recognizes ateganosine’s potential as a new therapeutic paradigm in cancer treatment science. Ateganosine is the first and only anticancer treatment of its kind that we are aware of in clinical development," stated MAIA Chairman and CEO Vlad Vitoc, M.D. "If we are successful in the Fast Track regulatory pathway, ateganosine could qualify for accelerated FDA approval and robust exclusivity in NSCLC, with a potential FDA decision as early as next year. If approved, ateganosine would have a first-to-market competitive position within a $34 billion NSCLC treatment market with significant unmet medical need."

NSCLC represents one of the largest global oncology indications. The market was valued at $34.1B in 2024 and is projected to reach $68.8B by 2033 with a projected CAGR of 8.1%.1

"This is an important milestone for MAIA’s clinical development program. Ateganosine has demonstrated robust preclinical efficacy and superior clinical median overall survival compared to other FDA-approved treatments for NSCLC patients with prior disease progression on platinum-based chemotherapy and anti-PD-(L)1 antibody. Additionally, advanced NSCLC is a devastating disease that clearly meets the criteria for a serious condition with unmet medical need. Both are key criteria for the Fast Track designation," said K. Robinson Lewis, Vice President, Head of Regulatory and Quality at MAIA. "We intend to utilize the incentives of the Fast Track Program to expedite the development and review of ateganosine and bring patient access sooner."

The FDA Fast Track is a process designed to facilitate development and expedite the review of drugs for treating serious conditions and filling an unmet medical need, as in providing a therapy where none exists or which may be potentially better than available therapy. If relevant criteria are met during the Fast Track process, a drug will be eligible for FDA Accelerated Approval and Priority Review (FDA decision within six months).

MAIA’s most recent data from the pivotal Phase 2 THIO-101 clinical trial of ateganosine as of May 15, 2025 showed median overall survival (OS) of 17.8 months in a heavily pre-treated population. As of the data cut-off date, the patient with the longest survival in the trial had completed 32 cycles of therapy and had 24.3 months survival. Studies of standard-of-care chemotherapy treatments for NSCLC in a similar setting have shown overall survival of 5 to 6 months.

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 of 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.

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 ateganosine’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of ateganosine administered prior to 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 another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of ateganosine administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of ateganosine using Overall Response Rate (ORR) as the primary clinical endpoint. The expansion of the study will assess overall response rates (ORR) in advanced NSCLC patients receiving third line (3L) therapy who were resistant to previous checkpoint inhibitor treatments (CPI) and chemotherapy. Treatment with ateganosine followed by cemiplimab (Libtayo) has shown an acceptable safety profile to date in a heavily pre-treated population. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

On July 27, 2025 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercialising first-in-class and/or best-in-class medicines for cancer, reported that an abstract featuring the latest data from a Phase I/II study of the Claudin 18.2 antibody-drug conjugate (ADC), ATG-022, has been accepted for poster presentation at the 2025 European Society for Medical Oncology Annual Congress (ESMO 2025), taking place from October 17th to October 21st at the Messe Berlin in Berlin, Germany (Press release, Antengene, JUL 27, 2025, View Source;302514585.html [SID1234654553]).

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Details of the Poster Presentation:

ATG-022 (Claudin 18.2 antibody-drug conjugate)
Title: Phase I/II study of Claudin 18.2 ADC ATG-022 in patients with advanced gastric/ gastroesophageal junction cancer (CLINCH)
Abstract Number: 2907
Presentation Number: 2113P
Date: October 19, 2025

About ATG-022

ATG-022 is an antibody-drug conjugate (ADC) designed to target CLDN18.2, a member of the Claudin family of cell adhesion molecules. Under normal conditions, Claudins are located within tight junctions between cells, forming a barrier to regulate cell permeability. However, in cancer, Claudins are aberrantly expressed on the cell surface due to changes in cell polarity. CLDN18.2 is frequently overexpressed in a range of primary malignant tumors, including gastric, esophageal, cholangiocarcinoma, and pancreatic cancers. The U.S. Food and Drug Administration (FDA) has awarded Orphan Drug Designations to ATG-022, for gastric and pancreatic cancers.

Data from the ongoing CLINCH study demonstrated that ATG-022 delivers robust efficacy across all levels of CLDN18.2 expression in gastric cancer patients, including those with high, low, and ultra-low expression. This broad activity positions ATG-022 as a potential market leader, capable of addressing the largest patient population with CLDN18.2-positive tumors. Furthermore, the strong efficacy observed in patients with low CLDN18.2 expression suggests promise for treating other tumor types with similar expression profiles.

On July 27, 2025 Hengrui Pharma (600276.SH; 01276.HK) reported it has entered into agreements with GSK plc (LSE/NYSE: GSK) to develop up to 12 innovative medicines, adding significant value to the globalization strategy of Hengrui and significant new growth opportunities to GSK beyond 2031 (Press release, Hengrui Pharmaceuticals, JUL 27, 2025, View Source;inflammation-and-oncology-302514566.html [SID1234654554]). The programmes were selected to complement GSK’s extensive Respiratory, Immunology & Inflammation (RI&I) and Oncology pipeline, and assessed for their potential best- or first-in-class profiles. GSK will pay $500 million in upfront fees across the agreements.

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The agreements include an exclusive worldwide license (excluding mainland China, Hong Kong SAR, Macau SAR and Taiwan region) for a potential best-in-class, PDE3/4 inhibitor (HRS-9821) in clinical development for the treatment of chronic obstructive pulmonary disease (COPD) as an add-on maintenance treatment, irrespective of background therapy. The addition of HRS-9821 supports GSK’s ambition to treat patients across the widest spectrum of COPD by including those who face continued dyspnoea (shortness of breath) or who are unlikely to receive inhaled corticosteroids or biologics, based on their disease profile.

HRS-9821 has demonstrated potent PDE3 and PDE4 inhibition, leading to increased bronchodilation and anti-inflammatory effects in early clinical and preclinical studies. In addition, HRS-9821 provides the opportunity for a convenient dry-powder inhaler (DPI) formulation that strategically fits GSK’s established inhaled portfolio.

The agreements also include a pioneering scaled collaboration to generate up to 11 programmes in addition to HRS-9821, each with its own financial structure. Hengrui Pharma will lead the development of these programmes up to completion of phase I trials, including patients outside of China. GSK will have the exclusive option to further develop and commercialise each programme worldwide (excluding mainland China, Hong Kong SAR, Macau SAR and Taiwan region), at the end of phase I or earlier at GSK’s election as well as certain programme substitution rights.

Frank Jiang, Executive Vice President and Chief Strategy Officer of Hengrui Pharma, said: "This strategic collaboration with GSK marks yet another significant milestone in Hengrui’s globalisation journey and our mission to innovate and deliver higher-quality, cutting-edge therapies for patients worldwide. GSK brings additional R&D expertise, a robust global clinical network, and broad regulatory capabilities that will accelerate our PDE3/4 inhibitor as well as an array of other innovative therapy programs to overseas markets, potentially delivering breakthrough treatments to patients globally."

Tony Wood, Chief Scientific Officer, GSK said: "We’re delighted to announce these exciting agreements with Hengrui Pharma which complement our already-extensive pipeline. This deal reflects our strategic investment in programmes that address validated targets, increasing the likelihood of success, and with the option to advance those assets with the greatest potential for patient impact."

The collaboration enables scale and speed to proof-of-concept to develop up to 11 additional innovative medicines. It benefits from GSK’s therapy area expertise, deep understanding of disease biology, clinical development capability and global commercial scale with Hengrui Pharma’s early discovery engine, platform technologies, extensive pre-clinical pipeline of high-value programmes and speed of clinical evaluation.

Financial considerations
GSK will pay $500 million in upfront fees across the agreements including for the license of the PDE3/4 programme. The potential total value of future success-based development, regulatory and commercial milestone payments to Hengrui Pharma is approximately $12 billion if all programmes are optioned and all milestones are achieved. In addition, Hengrui Pharma will be eligible to receive tiered royalties on global product net sales (excluding mainland China, Hong Kong SAR, Macau SAR and Taiwan region).

The license to HRS-9821 is subject to customary conditions, including applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the US.

On July 27, 2025 Harbour BioMed (the "Company"; HKEX: 02142), a global biopharmaceutical company focused on the discovery and development of novel antibody therapeutics in immunology and oncology, reported a positive profit alert for the six months ended June 30, 2025 (the "Reporting Period") (Press release, Harbour BioMed, JUL 27, 2025, View Source [SID1234654556]).

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Based on a preliminary review of the Company’s unaudited management accounts for the Reporting Period, total profit is expected to range between US$68 million (equivalent to approximately HK$532 million) and US$74 million (equivalent to approximately HK$579 million).

The anticipated increase in profit is primarily attributable to:

Continuing strategic partnerships with leading global pharmaceutical companies, including the global strategic collaboration with AstraZeneca.
– The Company has received gross proceeds totaling approximately US$175 million from the allotment and issuance of the subscription shares, as well as partial upfront, milestone, and option exercise fees.
Newly secured out-licensing and collaboration agreements for innovative products, which contributed significantly to revenue during the Reporting Period and are evolving into a normalized revenue stream of the Company.
Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed, commented: "This anticipated improvement in profitability underscores the meaningful progress we’ve made in executing our strategic priorities. The performance reflects the strength of our diversified business model and our ability to translate scientific innovation into tangible value. We will continue to build on this momentum through innovation and high-impact collaborations to deliver sustainable growth."