On September 11, 2025 Ferring Pharmaceuticals Co., Ltd. reported that the PMDA has accepted the NDA for nadofaragene firadenovec for review, following submission on August 27th, 2025 (Press release, Ferring, SEP 11, 2025, View Source [SID1234655932]). This non-replicating gene therapy, administered intravesically, offers patients with NMIBC a bladder-sparing treatment option. Nadofaragene firadenovec’s quarterly dosing eliminates the burden of frequent treatments, while delivering a non-chemotherapy mechanism of action through interferon gene therapy. The NDA acceptance further highlights Ferring’s ongoing commitment to establish the new standard of care for high-risk BCG- unresponsive NMIBC.

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Professor Keiji Inoue, M.D., Ph.D., Department of Urology, Kochi Medical School, stated: "Nadofaragene firadenovec represents an option for those who failed NMIBC treatment. As the first choice after BCG failure, this bladder sparing gene therapy offers patients a non-chemotherapy option that transforms their own bladder cells into interferon-producing factories. The 75% complete response rate achieved with convenient quarterly dosing provides hope for patients who previously faced limited treatment options."

The NDA for nadofaragene firadenovec is based on results from a Phase 3 trial conducted in Japan.1 The primary outcome of a complete response (CR) rate of 75% at 3 months, following a single dose in 20 high-risk Japanese patients with carcinoma in situ (CIS), with or without concomitant high-grade Ta or T1 papillary lesions, was presented at the 112th Annual Meeting of the Japanese Urological Association (JUA, April 17-19, 2025, Fukuoka). All treatment-related adverse events were limited to Grade 1 (84.2%) or Grade 2 (15.8%), with zero Grade 3, 4, or 5 adverse events reported – confirming the therapy’s favourable safety and tolerability profile.1

These results are consistent with independent US real-world data presented by the Mayo Clinic, which demonstrated 79% complete response rate.2 The results from the Mayo Clinic were achieved following a single quarterly dosing, representing clinical and convenience advantages over existing therapies, without requiring re-induction protocols.2 Patients who achieved complete response continued quarterly maintenance dosing.

Joern Jakobsen, M.D., Ph.D., Vice President and Head of Global Research and Medical for Uro-Oncology and Urology, Ferring Pharmaceuticals stated "Traditionally, when BCG therapy proved insufficient, patients had no choice but to undergo highly invasive treatments such as radical cystectomy or risk cancer progression. Nadofaragene firadenovec is expected to offer a new bladder-sparing treatment option. At Ferring, we are committed to addressing the unmet needs in bladder cancer treatment by providing urologists with critical insights that enable effective, personalized, and groundbreaking therapies."

"Our ambition is to establish nadofaragene firadenovec as the new standard of care and the backbone therapy for NMIBC treatment," said Bipin Dalmia, Global Head, Uro-Oncology & Urology Franchise. "High-risk NMIBC patients who no longer respond to BCG have endured decades of little progress and currently face bladder removal as their primary option. This PMDA acceptance validates our strategic commitment to bring this treatment to Japanese patients."

About nadofaragene firadenovec
Nadofaragene firadenovec represents the first and only FDA-approved intravesical non-replicating gene therapy for adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours.

As the first choice therapy following BCG failure, this non-chemotherapy approach utilises a non-replicating adenovirus vector-based therapy containing the interferon alfa-2b gene. Administered locally as convenient monotherapy by catheter directly into the bladder once every three months only, the mechanism transforms bladder wall cells into interferon microfactories, creating high and transient local expression of interferon alfa-2b protein – amplifying the body’s natural cancer-fighting capabilities through gene therapy rather than traditional chemotherapy approaches.

This therapeutic approach has been investigated through comprehensive clinical evaluation including 157 patients in the US with high-risk BCG-unresponsive NMIBC who demonstrated inadequate BCG response (full inclusion criteria published on clinicaltrials.gov: NCT02773849). 5-year follow-up data confirmed 80% overall survival rate and 49% cystectomy-free survival rate in adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumours (±Ta/T1), and in patients with high-grade Ta/T1 without CIS. Long-term safety profile maintained with most treatment emergent AEs remaining transient Grade 1 or 2 (66% of all patients studied), and 4% experiencing Grade 3 AEs3.

In the real world setting, between November 2023 and October 2024, 45 patients across three Mayo Clinic locations in the US were treated with nadofaragene firadenovec for BCG-unresponsive NMIBC. Out of 45 treated patients, 29 were included in the analysis.2 After a median follow-up of 8.2 months: 72% of patients showed a complete response or were free from high-grade recurrence at 3 months. 62% maintained this response at 6 months. 94% avoided bladder removal surgery (cystectomy). 100% were still alive at 6 months.

About Non-Muscle Invasive Bladder Cancer (NMIBC)
NMIBC affects the superficial bladder layer without deeper invasion or metastatic spread. Bladder cancer represents a major clinical challenge as the 13th most commonly diagnosed cancer in Japan and ninth globally,4 with 75% presenting as NMIBC in 2022.4 While intravesical BCG remains first-line standard care for high-risk NMIBC, over 50% of patients experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease requiring radical intervention.5

Current treatment options remain limited for BCG-unresponsive patients, with JUA guidelines recommending only radical cystectomy or clinical trial participation6. Nadofaragene firadenovec offers the first choice non-chemotherapy gene therapy option for these patients, providing an alternative to immediate radical surgery.

On September 11, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company focused on innovative cancer therapeutics, reported that it will host a premier KOL event on Thursday, Sept. 18th at 5 p.m. ET / 2 p.m. PT to discuss diverse perspectives on the Company’s interim efficacy results from a Phase 2 trial of its lead candidate, ENV105, in treating advanced prostate cancer patients (Press release, Kairos Pharma, SEP 11, 2025, View Source [SID1234655933]). Registration is required to participate in the webcast. Interested participants can sign-up to receive the webcast link here.

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"The safety results of the trial are an important catalyst as we prepare for the announcement of our interim efficacy results in treating prostate cancer patients. This predetermined efficacy analysis occurs four months after start of combination therapy of ENV105 and apalutamide in the last safety lead-in patient. We hope to lay out the primary benefits of our compound, and to clearly demonstrate the clinical need filled by ENV105," said Dr. John Yu, CEO of Kairos Pharma. "This distinguished panel of experts will provide participants with a renewed understanding of the importance of these data and the role ENV105 can have in targeting cancer drug resistance."

Speakers in the KOL event include Dr. Neil Bhowmick, President and Chief Scientific Officer at Kairos Pharma; Dr. Umang Swami, Associate Professor in the Division of Oncology, Department of Internal Medicine at the Huntsman Cancer Institute; Dr. Richard Lee, Clinical Co-Director, The Claire and John Bertucci Center for Genitourinary Cancers at Massachusetts General Hospital, Harvard Medical School, and Dr. Edwin Posadas, Director of the Experimental Therapeutics Program and the Medical Director of the Center for Uro-Oncology Research Excellence at the Samuel Oschin Comprehensive Cancer Institute.

The interim safety analysis of the trial, announced in July of this year, demonstrated that ENV105, a first-in-class CD105 antagonist, was well tolerated when combined with standard of care hormone therapy, apalutamide, from the first 10 enrolled patients. Thus far, there have been no dose-limiting toxicities or unexpected adverse events reported to date. In addition, the treatment-related side effects were manageable with standard supportive care. Notably, no Grade 3 or 4 toxicities were observed.

With one million men in the US diagnosed with prostate cancer each year, and millions more worldwide, the development of resistance to current hormone therapies is a growing unmet need with an increasingly aging population. Castration-resistant prostate cancer refers to tumors that grow despite receiving hormone blocking agents. Treatment options remain limited after hormone therapies fail. Kairos Pharma seeks to provide a safe and effective alternative for these patients with ENV-105.

On September 11, 2025 Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development company, reported new findings from a collaborative research program led by Professor Sudha Rao at QIMR Berghofer (Press release, Kazia Therapeutics, SEP 11, 2025, View Source [SID1234655934]).

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In this ex vivo study, blood samples from Stage IV HER2-positive metastatic breast cancer (mBC) patients were profiled to evaluate the effect of paxalisib, Kazia’s investigational PI3K–mTOR inhibitor, on metastatic burden. Paxalisib monotherapy demonstrated a statistically significant reduction in single circulating tumor cells and achieved a complete (100%) disruption of circulating tumor cell (CTC) clusters containing three or more cells."

Key Points
•
HER2-positive breast cancer accounts for 15–20% of cases and remains a clinical challenge despite the transformative impact of HER2-targeted therapies, with many patients experiencing resistance, recurrence, or metastasis.

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Immunotherapy has demonstrated success across several solid tumors but has shown limited efficacy in HER2-positive breast cancer, underscoring the need for new therapeutic approaches.

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In this study, liquid biopsy profiling of Stage IV patients revealed that paxalisib treatment effectively disrupted CTCs and CTC clusters, which are considered biomarkers of aggressive disease and metastasis.

•
Immunofluorescence analyses showed that paxalisib-treated blood samples from HER2-positive mBC patients achieved complete disruption of highly metastatic CTC clusters (≥3 cells).

"This monotherapy ex-vivo result extends our understanding of paxalisib’s potential beyond triple-negative breast cancer into HER2-positive disease," said Dr. John Friend, CEO of Kazia Therapeutics. "The ability to disrupt circulating tumor cell clusters, which are strongly associated with metastasis and poor prognosis, represents a transformative therapeutic avenue. We are particularly excited by the precision medicine aspect of this work, which leverages biomarkers to both track metastatic burden and guide therapeutic decisions. This work underscores Kazia’s commitment to expanding paxalisib’s utility across multiple subtypes of advanced breast cancer, addressing high unmet need in patients with limited options."

These findings complement Kazia’s ongoing Phase 1b trial in Stage IV triple-negative breast cancer (TNBC), where initial patient data announced in July 2025 demonstrated significant reductions in circulating tumor cells and clusters, underscoring the broader potential of paxalisib to address metastatic progression across multiple breast cancer subtypes.

Next Steps

Detailed datasets encompassing metastatic signatures and disrupted progenitor populations in Stage IV HER2-positive breast cancer have been submitted for presentation at an upcoming global oncology meeting in 2025.

On September 10, 2025 Exact Sciences Corp. (Nasdaq: EXAS), a leader in cancer diagnostics, reported the launch of the Cancerguard test, a new multi-cancer early detection (MCED) blood test that is now available as a laboratory-developed test (LDT) in the United States (Press release, Exact Sciences, SEP 10, 2025, View Source [SID1234655919]). Cancerguard is the first MCED test commercially available that analyzes multiple biomarker classes to help detect a wide range of cancers, including those that often go undiagnosed until later stages when treatment options are limited.

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Nearly 70 percent of annual cancer cases and deaths in the U.S. occur in cancers with no recommended screening.1,2,3 The Cancerguard test can help address the unmet need by complementing existing routine screening and extending the reach of early detection. With a simple blood draw, the Cancerguard test can detect signals from cancer types responsible for more than 80 percent of annual U.S. cancer diagnoses, including some with the highest mortality rates, such as pancreatic, ovarian, liver, esophageal, lung, and stomach cancers.1,4 Overall, the Cancerguard test can detect more than 50 cancer types and subtypes.5

The Cancerguard test delivered 68 percent sensitivity across six of the deadliest cancers and 64 percent overall sensitivity across a broader range of cancers, excluding breast and prostate, in test-development studies. It also found more than a third of stage I or II cancers, demonstrating its ability to detect disease when it’s most treatable.1,2,4* Additionally, the test achieved high specificity of 97.4 percent, helping to minimize false positives and avoid unnecessary procedures.4 Modeling shows that over a 10-year period, use of Exact Sciences’ MCED technology alongside current screening methods could reduce stage IV cancer diagnoses by 42 percent and lower overall cancer-related mortality by 18 percent.6 Together, these findings underscore the Cancerguard test’s potential to meaningfully improve outcomes and elevate the standard of cancer detection.

The Cancerguard test will be delivered through Exact Sciences’ expansive commercial and operational infrastructure, including a national sales force that engages primary care physicians, oncologists, and leading health systems. To support patient access, Exact Sciences has entered into an agreement with Quest Diagnostics to enable blood collection at the company’s approximately 7,000 patient access sites across the U.S., including through its patient service centers and in-office phlebotomists in provider offices, as well as mobile phlebotomy services for at-home collections.

"Cancerguard builds on the legacy of Cologuard, which has delivered more than 20 million test results and transformed colorectal cancer screening," said Kevin Conroy, chairman and CEO of Exact Sciences. "Backed by strong science and developed to screen for many of the deadliest cancers, the Cancerguard test represents the next bold step in our mission to detect cancer earlier. With deep, trusted relationships across the health care system, Exact Sciences has the reach, credibility, and commitment to bring earlier answers to more people. This is the moment where we begin to change the course of cancer forever and give people power over their futures."

The Cancerguard test is the culmination of nearly a decade of development and is backed by rigorous science in partnership with top academic institutions. The test is supported by data from robust test-development studies, such as DETECT-A and ASCEND 2, involving more than 20,000 participants, including the first-ever prospective interventional MCED trial.7,8,9 To further validate clinical utility and support broad adoption, Exact Sciences is actively enrolling up to 25,000 participants in the Falcon registry, a real-world evidence study conducted under a U.S. FDA-reviewed Investigational Device Exemption (IDE).10 This comprehensive body of evidence is designed to inform future regulatory submissions, support payer discussions on coverage and reimbursement, and guide efforts to include the Cancerguard test in clinical guidelines.

"The Cancerguard test offers a critical early warning that cancer may be present and helps inform an imaging-guided pathway to diagnosis, giving people the chance to act when it matters most," said Dr. Tom Beer, chief medical officer for multi-cancer early detection at Exact Sciences. "As adoption grows, we’ll look back and ask how we ever settled for screening for only a few cancers while letting the majority go undetected. Like the smartphone redefined communication, Cancerguard has the power to redefine cancer detection and the future of early intervention."

Exact Sciences delivers the Cancerguard test with comprehensive support for both patients and clinicians. The test integrates seamlessly into existing workflows and electronic medical records (EMRs) and is backed by industry-leading care navigation support, including dedicated support for patients with positive results. The Cancerguard test is recommended for individuals aged 50-84 with no known cancer diagnosis in the past three years and can be considered annually. It is priced at $689 and may be eligible for flexible spending and health savings account use, with payment plans available. Additional financial support includes a patient imaging assistance program** to help reduce the impact of non-covered imaging costs for eligible patients. The Cancerguard test is currently available for providers to order at www.exactsciences.com/cancerguard, with broader consumer telehealth access beginning in October 2025 at www.cancerguard.com.

On September 10, 2025 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported that FDA has granted Fast Track designation for GLSI-100 in the HLA-A*02 patient population (Press release, Greenwich LifeSciences, SEP 10, 2025, View Source [SID1234655920]).

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The designation specifically states that "GLSI-100 for the treatment of patients with HLA-A*02 genotype and HER2-positive breast cancer who have completed treatment with standard of care HER2/neu targeted therapy to improve invasive breast cancer free survival meets the criteria for Fast Track designation."

The Fast Track designation for GLSI-100 may lead to earlier drug approval as the Company and the FDA can communicate more frequently to expedite the Biologic License Application (BLA) filing of the clinical and manufacturing data from FLAMINGO-01. The Company may be able to utilize a rolling review process, where completed parts of the BLA can be submitted for review, even though other parts of the application are still being completed.

Dr. Jaye Thompson, VP Clinical and Regulatory Affairs, commented, "Greenwich is pleased that the FDA sees the potential of GLSI-100 to change important clinical outcomes in this population of breast cancer patients. We continue to work earnestly to collect data to support a BLA filing demonstrating this benefit."

CEO Snehal Patel commented, "We are excited to have received Fast Track designation. The FDA review of our Fast Track application included a review of the potential of GLSI-100 as a new drug to treat serious conditions and to fill unmet medical need. By showing the potential of GLSI-100 to prevent metastatic breast cancer recurrence in the patient population that we are studying, we were able to estimate the potential lives that could be saved. The Company plans to continue discussions with the FDA, and potentially the European regulatory authorities, to explore additional ways to make GP2 and GLSI-100 available to larger populations."

A description of the Fast Track criteria and process is available on the FDA website:
View Source

As described by the FDA website:

"Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions…Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy…Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients."

The FDA website further states:

"Any drug being developed to treat or prevent a condition with no current therapy obviously is directed at an unmet need. If there are available therapies, a fast track drug must show some advantage over available therapy, such as:

Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
Avoiding serious side effects of an available therapy
Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
Ability to address emerging or anticipated public health need
A drug that receives Fast Track designation is eligible for some or all of the following:

More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA"
Previously Published Phase IIb Data

In the prospective, randomized, single-blinded, placebo-controlled, multi-center (16 sites led by MD Anderson Cancer Center) Phase IIb clinical trial of HLA-A*02 breast cancer patients, 46 HER2/neu 3+ over-expressor patients were treated with GLSI-100, and 50 placebo patients were treated with GM-CSF alone. After 5 years of follow-up, there was an 80% or greater reduction in cancer recurrences in the HER2/neu 3+ patients who were treated with GLSI-100, followed, and remained disease free over the first 6 months, which we believe is the time required to reach peak immunity and thus maximum efficacy and protection. The Phase IIb results can be summarized as follows:

80% or greater reduction in metastatic breast cancer recurrence rate over 5 years of follow-up compared to 20-50% reduction in recurrence rate by other approved products
Peak immune response at 6 months
No reported serious adverse events attributable to treatment
Well-tolerated safety profile
Full immunization was received in the Primary Immunization Series (PIS), which included the first 6 GLSI-100 injections over the first 6 months. The PIS elicited a potent immune response as measured by local skin tests and immunological assays. Further, booster injections given every 6 months prolonged the immune response, thereby providing longer-term protection. In the Phase IIb and three Phase I clinical trials, where 146 patients were treated, the GP2 immunotherapy was well tolerated, and there were no reported serious adverse events related to GLSI-100.

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US and European clinical sites from university-based hospitals and academic and cooperative networks with plans to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.