On September 8, 2025 ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, reported new paradigm changing findings from the Phase 2 QUILT-3.055 study, demonstrating ANKTIVA (nogapendekin alfa inbakicept-pmln) reverses lymphopenia (low natural killer and T cells) in patients with checkpoint inhibitor-resistant advanced non-small cell lung cancer (NSCLC), with this reversal resulting in significant prolonged median overall survival (mOS) (Press release, ImmunityBio, SEP 8, 2025, View Source [SID1234655829]). The results were presented (P1.11.78) on Sunday, September 7, at the IASLC 2025 World Conference on Lung Cancer in Barcelona, Spain. A video presentation of the data is available on X.com @DrPatSoonShiong.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Severe lymphopenia (loss of cancer-killing natural killer cells and T cells), is defined by the absolute lymphocyte count (ALC) of less than 1,000 lymphocyte cells/µL. This lowered ALC count is caused by the side effects resulting from current standards of treatment with radiotherapy, chemotherapy and immunotherapy, and is associated with reduced survival across all tumor types.1,2 Although reduced ALC is a recognized risk factor in a many cancers, it has largely been overlooked because no therapies have been approved to address lymphopenia. ANKTIVA is the first therapy under investigation specifically for this purpose.

"These results present the clinical evidence that a low lymphocyte count, as measured by ALC levels, is an actionable, accessible biomarker to identify and treat therapy-induced lymphopenia in cancer patients with ANKTIVA and prolong overall survival," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "ANKTIVA is the first FDA-approved immunotherapy to stimulate natural killer cells, CD4+ CD8+ T cells and memory T cells, the very cells that are depleted resulting in lymphopenia, and that play a key role in the immune system’s fight against cancer. It is my belief that treating lymphopenia in patients with low NK and T cell count, is as essential as the well-established treatment of anemia (low red blood cells count) or of neutropenia (low neutrophil count), which occur as a consequence of chemotherapy, independent of tumor types. By taking this approach, we hope to herald in the paradigm change of treating the immune system itself and thereby allow the immune system to cure the cancer, regardless of its anatomical location. The long-term survival demonstrated in patients with bladder cancer and now in lung cancer provide evidence of the potential validity of this hypothesis, with ANKTVIA as the foundation of the BioShield platform."

Specific findings from the Phase 2 QUILT-3.055 study include:

Participants with a baseline ALC≥1,200 cells/µL and a group mean ALC≥1500 cells/µL at each on-treatment time point (N=44) had greater prolonged OS (21.1 months, 95% CI: 13.9. 42.1)
mOS for study participants with NSCLC, including patients in second line (51%) and third line-plus treatment (49%), was 14.3 months (95% CI 11.7, 17.4), with 23 of 86 participants alive at data cutoff (December 2024)
Among patients treated with ANKTIVA, 80% (69 of 86) exceeded an ALC of 1,200 cells/µL, with mOS of 15.8 months (95% CI 12.6, 21.9) compared to participants who failed to achieve ALC>1,200 cells/µL with mOS of 11.5 months (95% CI 4.2, 13.3); p=0.0057
60% of participants (25/42) treated with ANKTIVA reversed their lymphopenia during at least one on-treatment timepoint.
The randomized Phase 3 ResQ201A trial (NCT06745908) is evaluating ANKTIVA + tislelizumab, a checkpoint inhibitor, versus docetaxel alone in second-line NSCLC patients who have progressed after all standard therapies, including checkpoint inhibitors. Patients interested in enrolling can inquire at org.
The Phase 2 QUILT-3.055 study (NCT03228667) enrolled participants with advanced NSCLC who had developed resistance to checkpoint inhibitor immunotherapy (CPI). Participants continued treatment with the same CPI on which they had progressed, combined with ANKTIVA, to test the hypothesis that AKNTIVA could improve overall survival by reversing lymphopenia and maintaining median ALC≥1,200 cells/µL. The primary endpoint was the change in ALC, including absolute cell count and percentage change from baseline, with ANKTIVA plus CPI during the study and its relationship to mOS. Statistical differences between OS among participants who failed to reverse lymphopenia (ALC<1,200 cells/µL) during treatment vs. those who had a baseline ALC≥1200 cells/µL and maintained a group mean ALC≥1,500 cells/µL while on treatment were compared. The study also assessed the proportion of participants with lymphopenia reversal (baseline ALC<1,200 cells/µL and at least one on-treatment ALC≥1,200 cells/µL).

ANKTIVA is currently approved by the U.S. Food and Drug Administration with Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.

About ANKTIVA (nogapendekin alfa inbakicept-pmln)

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response. A key component in the company’s BioShield platform, ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and driving the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones.

IMPORTANT SAFETY INFORMATION

INDICATION AND USAGE: ANKTIVA is an interleukin-15 (IL-15) receptor agonist indicated with Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

WARNINGS AND PRECAUTIONS: Risk of Metastatic Bladder Cancer with Delayed Cystectomy. Delaying cystectomy can lead to the development of muscle-invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after a second induction course of ANKTIVA with BCG, reconsider cystectomy.

DOSAGE AND ADMINISTRATION: For Intravesical Use Only. Do not administer by subcutaneous or intravenous routes.

Please see the complete Indication and Important Safety Information and Prescribing Information for ANKTIVA at Anktiva.com.

On September 8, 2025 Atossa Therapeutics, Inc. (Nasdaq: ATOS; "Atossa" or the "Company") reported it has requested a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss a regulatory strategy aimed at accelerating development of low-dose (Z)-endoxifen for breast cancer risk reduction (Press release, Atossa Therapeutics, SEP 8, 2025, View Source [SID1234655844]). Atossa is a clinical-stage biopharmaceutical company developing new approaches in breast cancer treatment and risk-reduction, commonly termed prevention of breast cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Beginning in June 2025, Atossa engaged an internationally recognized FDA law firm and senior regulatory affairs experts to review the Company’s extensive (Z)-endoxifen data and the considerable published scientific literature on (Z)-endoxifen. They evaluated whether existing evidence could support a faster regulatory path in breast cancer risk-reduction, specifically, in the adjuvant setting, in ductal carcinoma in situ (DCIS), and in high-risk women without cancer.

The experts recommended Atossa rapidly schedule a Type C meeting with the FDA to align on the requirements needed to complete a New Drug Application (NDA). Atossa has now filed this meeting request and expects to update shareholders on the outcome of the meeting before year end 2025, based on standard agency timelines. While there can be no assurance of success, a favorable meeting outcome could shorten approval timelines by years and avoid tens of millions of dollars in clinical trial costs. Atossa had approximately $57.9 million in cash and no debt as of June 30, 2025.

Market opportunity for low-dose (Z)-endoxifen

An estimated 1.6 to 2.1 million tamoxifen prescriptions are filled annually in the United States, including in three breast cancer risk-reduction settings:

Adjuvant therapy (post-surgery recurrence risk-reduction): According to the American Cancer Society, approximately 4.3 million U.S. women are living with a history of breast cancer, as of January 1, 2025. About 79 percent of U.S. breast cancers are hormone-receptor positive. Professional guidelines recommend ≥5 years of adjuvant endocrine therapy, for these patients, with extension to 7–10 years in selected, higher-risk cases. Approximately 1 million women are currently taking adjuvant endocrine therapy in the U.S. based on initiation and real-world persistence data.

Risk reduction following DCIS surgery: It is estimated that a few hundred thousand women are taking SERMs or aromatase inhibitors for breast-cancer risk-reduction, including post-DCIS and other high-risk settings in the U.S. DCIS alone likely accounts for up to 80,000 women on therapy at any given time.

Risk reduction in high-risk women without prior cancer: 2010 NHIS data estimated that roughly 120,000 U.S. women are using preventive SERM therapy for primary risk-reduction.
In addition, approximately 600,000–800,000 women are currently taking an aromatase inhibitor as adjuvant endocrine therapy in the U.S. About one-third to one-half experience musculoskeletal symptoms on AIs (pooled prevalence about 46 percent) and more than 30 percent discontinue treatment early due to those symptoms (e.g., about 32 percent within two years in a large prospective cohort).

(Z)-Endoxifen has demonstrated equivalent anti-estrogen pharmaceutical activity to tamoxifen, but with important differences. It avoids the CYP2D6 metabolism variability of tamoxifen, in which up to 20 percent of women do not achieve a therapeutic level of (Z)-endoxifen following tamoxifen administration. This exposure variability is well-documented and contributes to inconsistent endoxifen levels on tamoxifen; recurrence rates of 30 percent despite adjuvant therapy highlight the residual unmet need.

In Atossa clinical trials, direct oral (Z)-endoxifen achieved high systemic (Z)-endoxifen concentrations independent of CYP2D6 metabolism, whereas during tamoxifen therapy (Z)-endoxifen constitutes approximately six percent of the total tamoxifen-related metabolites at steady state.

In addition, tamoxifen takes four weeks to reach plasma steady state and its primary intermediate (N-desmethyl-tamoxifen) takes eight weeks. Direct (Z)-endoxifen can achieve target endoxifen concentrations within hours and typically reaches steady state within about one week in clinical studies.

Complementary Role of Project Optimus

Atossa continues to advance its FDA-aligned Phase 2 Project Optimus trial to identify the optimal (Z)-endoxifen dose in metastatic breast cancer. We believe this program not only supports the development of endoxifen in the metastatic setting but also strengthens the scientific and regulatory bridge for development in the low dose risk-reduction setting.

Dr. Steven Quay, Chairman and CEO of Atossa, commented, "This new regulatory strategy could dramatically accelerate the timeline for the development and potential approval of low-dose (Z)-endoxifen in the reduction of the incidence of breast cancer. We see a potential multi-billion-dollar market opportunity given the number of women currently on tamoxifen in the risk-reduction settings, and of women on aromatase inhibitors, half of whom experience painful arthritic symptoms. Importantly, this strategy could bring (Z)-endoxifen to patients, years sooner, at lower cost, and with a more predictable and faster-acting therapy than tamoxifen."

About (Z)-Endoxifen

(Z)-endoxifen is a highly potent Selective Estrogen Receptor Modulator/Degrader (SERM/D) with demonstrated ability to inhibit and degrade estrogen receptors. It has shown activity even in tumors that have developed resistance to other endocrine therapies. Beyond its anti-estrogenic properties, (Z)-endoxifen also targets the oncogenic signaling pathway, protein kinase C beta 1 (PKCβ1), at clinically achievable blood and tumor levels. (Z)-Endoxifen also seems to deliver comparable or superior bone-protective effects relative to tamoxifen.

Atossa is developing a proprietary enteric oral formulation of (Z)-endoxifen that bypasses stomach acid, which would otherwise partially convert the active (Z)-isomer to its inactive (E)-form. We believe this innovation allows for optimal bioavailability and therapeutic integrity. Clinical studies have shown Atossa’s (Z)-endoxifen to be well tolerated in both healthy women and those with breast cancer. In over 700 subjects (healthy volunteers and breast cancer patients) receiving doses up to 360 mg/day, no maximum tolerated dose (MTD) has been identified, supporting continued dose-range exploration.

Atossa is prioritizing development in metastatic breast cancer. In parallel, (Z)-endoxifen is being evaluated in three Phase 2 studies, one in DCIS and two in ER+/HER2- breast cancer. Monotherapy in DCIS and low risk cancer, and combination therapy in high-risk cancer, with Lilly’s CDK4/6 inhibitor, Verzenio (abemaciclib), are being investigated. Atossa’s (Z)-endoxifen program is supported by a growing global intellectual property portfolio, including three recently issued U.S. patents and numerous pending applications worldwide.

On September 8, 2025 Integra Therapeutics, a global leader in cutting-edge gene writing tools to improve the efficacy, precision and safety of advanced therapies, reported it has closed a €10.7 million pre Series A round of investment (Press release, Integra Therapeutics, SEP 8, 2025, View Source [SID1234655830]). The funds come from new investors like the EIC Fund —the venture capital arm of the European Innovation Council (EIC) with the European Investment Bank (EIB) as the investor of record—, which invested €4 million, and CDTI Innvierte of the Spanish Ministry of Science, Innovation and University, which contributed €2.7 million, as well as from existing investors AdBio Partners, Columbus Venture Partners, Invivo Partners and Takeda Ventures, which continue to support the company’s vision.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The funds will be used to incorporate new advances into the FiCAT gene writing platform, validate various next generation CAR-T therapies in the preclinical phase and expand the FiCAT cell engineering capabilities to facilitate technology transfer to the pharmaceutical industry. In May, the company announced new, highly promising preclinical data for its FiCAT platform at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper).

Moreover, Integra is developing its first gene therapy for a rare pediatric liver disease, funded by an EIC Accelerator grant.

"Thanks to the support of our investors, we will continue leading innovation in cell and gene therapies and are getting closer to transforming the treatment of complex diseases like cancer, autoimmune diseases and rare diseases," explains Avencia Sánchez-Mejías, PhD, CEO and Co-Founder of Integra Therapeutics.

"We are happy to announce EIC Fund’s investment in Integra Therapeutics. We empower them to accelerate the development of groundbreaking therapies that have the potential to transform lives and advance the field of gene therapy on a global scale," says Svetoslava Georgieva, Chair of the EIC Fund Board.

On September 8, 2025 PhotonPharma, a biotechnology company developing next-generation cancer immunotherapies, reported the issuance of U.S. Patent No. 12,280,039 B2 titled "Cancer Vaccine Compositions and Methods of Use Thereof (Press release, PhotonPharma, SEP 8, 2025, View Source [SID1234655845])." The patent, issued by the United States Patent and Trademark Office on April 22, 2025, covers the Company’s proprietary method for producing cancer immunotherapy products using photochemically-inactivated cancer cells that maintain immunogenic properties.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Novel Approach to Cancer Immunotherapies

The patented technology, Innocell, represents a significant potential advancement in cancer therapies. Riboflavin (vitamin B2) acts as a photosensitizer that when combined with UV light, inactivates cancer cells while preserving critical tumor antigens. This innovative approach addresses a fundamental challenge in cancer immunotherapy: how to effectively present tumor antigens to the immune system to stimulate immune response specific to the patient’s own tumor.

Key advantages of technology include:

Product Profile: Cancer cells are rendered completely incapable of replication while maintaining their antigenic properties. Cancer cells with enhanced antigen presentation are produced and can be used to stimulate a broad immune response to the patient’s tumor.

Preserved Immunogenicity: Critical surface markers and tumor-associated antigens remain intact for immune recognition. Cell metabolism is preserved. These altered cells can stimulate an immune response that has been demonstrated to target tumor cell destruction in pre-clinical studies.

Scalable Manufacturing: The photochemical inactivation process is rapid, reproducible, and suitable for clinical-scale production.

Broad Applicability: The technology can be applied across multiple cancer types and stages.
Compelling Preclinical Data

The patent includes extensive preclinical validation demonstrating the technology’s potential:

Tumor Growth Inhibition: Significant reduction in tumor growth rates in multiple animal models

Enhanced Survival: Extended survival times compared to control groups in efficacy studies

Immune System Activation: Robust T-cell responses and immunological memory formation
"This patent issuance validates our innovative approach to cancer immunotherapy and strengthens our intellectual property portfolio as we advance toward clinical trials," said Alan Rudolph, Ph.D., PhotonPharma Inc. board member. "Our technology has the potential to transform recurrent ovarian cancer treatments, offering patients a safer and more effective option."

According to the National Cancer Institute (View Source), ovarian cancer will impact 20,890 women in the US with 12,730 deaths in 2025 alone. The average five-year relative survival rate is 51.6% (2015-2021).

Strategic Value and Market Opportunity

The global Cancer Immunotherapy Market Size is projected to reach between $231-277 billion (CAGR 13.6% – 11.9%) by 2031 driven by increasing cancer incidence and growing adoption of immunotherapy approaches (Statista 2025, BioSpace 2022). This patent positions PhotonPharma at the forefront of next-generation cancer immunotherapy development.

Development Timeline

PhotonPharma is initiating Phase I trials, targeting recurrent epithelial ovarian cancer patients.

On September 8, 2025 OncoC4, Inc., a late-stage biopharmaceutical company developing novel medicines for cancer reported that it will have a poster presentation at the upcoming World Conference on Lung Cancer (WCLC) 2025 hosted by the International Association for the Study of Lung Cancer (IASLC), taking place September 6-9, 2025 in Barcelona, Spain (Press release, OncoC4, SEP 8, 2025, View Source [SID1234655992]). The presentation will feature the pivotal trial Stage II design for PRESERVE-003 (NCT05671510), a two-stage, randomized, open-label, active-controlled Phase 3 Study evaluating gotistobart monotherapy compared to docetaxel in squamous non-small cell lung cancer (sqNSCLC) after progression on a PD-(L)1 inhibitor.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Squamous NSCLC is among the deadliest cancers with very limited treatment options following traditional chemotherapy and immunotherapy (IO) with immune checkpoint inhibitors1. OncoC4 and its strategic partner BioNTech have embarked on this indication based on encouraging Phase 1/2 results and the match between the vulnerability of the sqNSCLC and the mechanism of action of gotistobart (ONC-392/BNT316). The Stage I of the 2-stage PRESERVE-003 study was designed for dose confirmation based on safety, efficacy and exposure-response analyses. The data supported selecting the high dose for Stage II, which consists of 1:1 randomization between gotistobart and docetaxel in patients with squamous NSCLC. Enrollment of Stage II (potentially registrational) continues to progress well with nearly 160 active sites worldwide.

Gotistobart is a next generation, acid pH-sensitive anti-CTLA-4 monoclonal antibody candidate that avoids antibody-induced lysosomal target degradation for better therapeutic index. Together with modifications in Fc, gotistobart induces more potent and selective depletion of regulatory T cells in the tumor microenvironment.

"The mechanism of action of gotistobart has the potential for clinical development of the drug beyond lung cancers for other indications with unmet medical needs, either as monotherapy or in combination with other therapeutic modalities," said Yang Liu, PhD, Co-Founder, Chief Executive Officer (CEO), and Chief Scientific Officer (CSO) of OncoC4.

WCLC Poster Presentation Details

Title: PRESERVE-003: A Phase 3 Study of Gotistobart Versus Docetaxel in Metastatic NSCLC
After Progression on PD-(L)1 Inhibitors (NCT05671510)

Abstract Number: 1363

Session: P3.18 – Ongoing Clinical Trials

Date: Tuesday, September 9, 2025

Time: 10:00 AM CEST

Presenter: Dr. Tianhong Li, Professor, Department of Internal Medicine, Division of Hematology and Oncology at UC Davis Comprehensive Cancer Center, CA

About PRESERVE-003

PRESERVE-003 is a randomized, open label, active controlled, multi-center Phase 3 trial (ClinicalTrials.gov NCT 05671510) sponsored by OncoC4 and consists of two stages. Stage 1, the dose-confirmation stage, assessed the efficacy and safety of two gotistobart dosing regimens (3 mg/kg Q3W and 6 mg/kg Q3W with 2 loading doses of 10 mg/kg Q3W) in comparison to docetaxel 75 mg/m2 Q3W in patients with squamous and non-squamous non-small cell lung cancer (NSCLC). Stage 2 assesses the safety and efficacy of gotistobart at 6 mg/kg Q3W with 2 loading doses of 10 mg/kg versus docetaxel (75 mg/m2 Q3W) on squamous cell NSCLC. The primary endpoint is Overall Survival.

About gotistobart (BNT316/ONC392)

Gotistobart is licensed to BioNTech for commercialization and jointly developed clinically by OncoC4 and BioNTech for oncology indications. There are several ongoing clinical trials in different tumor types, investigating gotistobart either as monotherapy or in combination with other therapeutic agents.

About squamous non-small cell lung cancer (NSCLC)

Squamous cell non-small cell lung cancer makes up 25 – 30% of all lung cancers, and is the most common lung cancer found in smokers2. In the US, first-line treatment for metastatic squamous NSCLC commonly involves a combination of chemotherapy and immunotherapy. However, treatment choices diminish when patients progress on prior IO options.