On February 19, 2025 Boehringer Ingelheim reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review to its new drug application for zongertinib (BI 1810631) for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) mutations and who have received prior systemic therapy (Press release, Boehringer Ingelheim, FEB 19, 2025, View Source [SID1234650392]). The FDA grants Priority Review to applications for drugs that would offer significant improvements in the treatment, diagnosis, or prevention of serious conditions, with action expected within six months compared to 10 months under standard review. The Prescription Drug User Fee Act (PDUFA) action date is in the third quarter of 2025.

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"We believe zongertinib has the potential to transform the care of previously treated patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer and are hopeful about the continued research in other tumor types and lines of therapy," said Shashank Deshpande, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. "Priority Review illustrates the urgent need in this patient population and the possibility for zongertinib to be a groundbreaking innovation for patients with limited treatment options."

The application was based on results from the positive Phase Ib Beamion LUNG-1 trial. Data from Cohort 1 (N=75) of the study demonstrated an objective response rate (ORR) of 71% with six-month progression-free survival (PFS) and duration of response (DoR) rates of 69% and 73%, respectively, in patients with mutations in the HER2 tyrosine kinase domain.

Zongertinib had a safety profile with a low incidence of dose reductions (5%) and treatment discontinuations (3%). The majority of treatment-related adverse events (TRAEs) with zongertinib were mild in nature with diarrhea and rash being the most common all grade TRAEs, at 51% and 27% respectively. No new safety signals were observed. Grade 3 or higher TRAEs occurred in one patient treated with zongertinib. No treatment-related interstitial lung disease (ILD) cases were reported.

"Personalized medicine has revolutionized cancer treatment," said GO2 for Lung Cancer’s Chief Scientific Officer, Courtney Granville. "Early screening and biomarker testing for mutations provide critical information to guide targeted therapies in personalized medicine. This filing acceptance represents a significant step toward offering another option for individuals with a HER2 (ERBB2) diagnosis, bringing hope and direction to cancer patients."

Zongertinib was previously granted Breakthrough Therapy Designation and Fast Track Designation by the FDA. The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of a medicine that is intended to treat a serious or life-threatening disease, and preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available treatments. The FDA’s Fast Track program is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. In addition to the FDA designations, Japan’s Pharmaceuticals and Medical Devices Agency recently granted Orphan Drug Designation to zongertinib.

About the Beamion clinical trial program
Beamion LUNG-1 (NCT04886804) is an open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with unresectable or metastatic solid tumors with HER2 (ERBB2) alterations. Beamion LUNG-2 is a Phase III, open label, randomized, active-controlled study that is enrolling patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain mutations to evaluate zongertinib compared with standard of care.

About zongertinib
Zongertinib (also known as BI 1810631) is an investigational, irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 (ERBB2) while sparing EGFR, thereby limiting associated toxicities. This orally administered, targeted treatment is being developed for HER2 (ERRB2)-mutant advanced non-small cell lung cancer (NSCLC) and additional clinical studies with zongertinib are ongoing in solid tumors with HER2 alterations.

About non-small cell lung cancer (NSCLC)
Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.ii NSCLC is the most common type of lung cancer.iii Due to a lack of symptoms and misdiagnoses,iv most patients diagnosed with NSCLC present at stage III or IV, where the disease has metastasized locally or to other organs.v Fewer than 3 in 10 patients are alive five years after a diagnosis of HER2 (ERBB2)-mutant advanced NSCLC.vi People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. HER2 (ERBB2) mutations occur in approximately 2–4% of NSCLC cases and are associated with a poor prognosis and higher incidence of brain metastases.vii,viii Mutations in HER2 (ERBB2) can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.

On February 19, 2025 Genmab A/S (Nasdaq: GMAB) reported that its Chief Financial Officer Anthony Pagano and Chief Development Officer Judith Klimovsky will participate in a fireside chat at the 45th Annual TD Cowen Health Care Conference in Boston, Massachusetts at 1:50 PM EST (7:50 PM CET) on March 3, 2025 (Press release, Genmab, FEB 19, 2025, View Source [SID1234650376]). A webcast of the fireside chat will be available on Genmab’s website at View Source

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On February 19, 2025 Pusan national university reported that Colorectal cancer (CRC) is one of the most prevalent types of cancer and has a high mortality rate globally (Press release, Pusan National University, FEB 19, 2025, View Source [SID1234650393]). Oral administration of anticancer drugs that pass through the gastrointestinal (GI) tract into the colorectum is a common strategy to deliver drugs in CRC treatment. However, this approach presents distinct challenges: most of these drugs lack target-specificity, leading to off-target side effects; these drugs get easily adsorbed onto the microvilli structure of the small intestinal epithelium, resulting in premature drug loss; and systemic drug absorption reduces CRC-targeted drug delivery. These challenges result in insufficient drug accumulation in the tumor cells and reduce the therapeutic efficiency of CRC treatment. Therefore, an innovative drug delivery strategy is urgently needed to ensure localized, precise CRC therapy.

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To address these challenges, a team of researchers led by Prof. Jin-Wook Yoo from Pusan National University, Republic of Korea, developed a unique drug delivery strategy for CRC therapy. In their exciting work, they proposed a drug delivery strategy by enclosing CRC cell-activated nanoconjugates (CTNCs) inside an alginate (Alg) matrix for highly specific and localized drug release. Prof. Yoo explains, "The main aim of this study is to develop CTNCs-in-alginate (Alg/ CTNCs) by synthesizing a hyaluronic acid (HA)-Poly (D, L-lactide-co-glycolide) (PLGA)-irinotecan (IRI) copolymer (HPI), followed by self-assembly for nanoconjugate formation and incorporation into an alginate matrix for highly CRC-specific oral drug delivery that bypasses the systemic circulation". This paper was made available online on 3rd January 2025 and to be published in Volume 505 of the Chemical Engineering Journal on 1st February 2025.

The alginate matrix transitions from a solution-like form to a gel-like form when exposed to the harsh acidic environment of the stomach and intestine, and shields the nanoconjugates, thus suppressing premature drug loss. Upon exposure to the basic pH in the colorectum, it converts back to the solution-like form, and deshields the nanoconjugates, thus delivering the CTNCs to the target tumor cells. The deshielded CTNCs readily interact with the CD44 receptor on the tumor cells via the HA ligand of CTNCs. Once the CTNCs are selectively internalized by CRC cells, the intracellular esterase of the tumor cells cleaves irinotecan from the HPI copolymer, ensuring highly target-specific drug release in vitro and in vivo. Prof. Yoo further explains their results, "The sol-gel transition in the stomach aids in shielding the CTNCs from unwanted interactions with the small intestine epithelium, resulting in facilitated passage and minimized IRI loss before reaching the colorectum. Additionally, completely deshielded CTNCs can be selectively internalized by CRC cells, followed by cancer esterase-triggered drug release within CRC cells, resulting in potent local anticancer effects without systemic side effects".

This study presents the successful development of a potential orally administrable drug delivery system that can bypass systemic circulation and precisely target CRC by leveraging the sol-gel-sol transition of alginate in the GI tract. "These findings highlight the potential of reversible shielding/deshielding and target cell-activated drug releasing strategies for the highly selective oral delivery of various therapeutics, such as small molecules, antibodies, and nucleic acid-based drugs, to disease sites in the colorectum", Prof. Yoo adds. The proposed drug delivery strategy can also be extended to treat other colorectum-specific diseases, such as ulcerative colitis.

Reference
Title of original paper: On-site sol-gel-sol transition of alginate enables reversible shielding/ deshielding of tumor cell-activated nanoconjugates for precise local colorectal cancer therapy
Journal: Chemical Engineering Journal
DOI: View Source

On February 19, 2025 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company entering a pivotal Phase 3 trial of its DNA-mediated immunotherapy, reported new translational data from ongoing analyses of results from the Company’s Phase 2 OVATION 2 Study of IMNN-001, its investigational interleukin-12 (IL-12) immunotherapy based on the company’s proprietary TheraPlas technology, for the treatment of newly diagnosed advanced ovarian cancer (Press release, IMUNON, FEB 19, 2025, View Source [SID1234650377]). Results demonstrated a 20% increase in IL-12 levels in women treated with IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus standard-of-care (SoC) neoadjuvant and adjuvant chemotherapy (NACT) compared to IL-12 levels in women treated with IMNN-001 (79 mg/m2).

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"These new data from the OVATION 2 Study confirm what we saw in the Phase 1 study and build on the robust body of evidence supporting the safety and strong overall survival results achieved with IMNN-001. These data also give us new levels of insight confirming the potential of our TheraPlas technology platform," said Stacy Lindborg, Ph.D., president and chief executive officer of IMUNON. "We are especially pleased that we continue to observe a highly positive benefit-risk profile of IMNN-001, the first immunotherapy to achieve clinically effective progression-free and overall survival in advanced ovarian cancer in conjunction with chemotherapy. We look forward to advancing this program to a Phase 3 pivotal trial, which remains on track to start this quarter."

In this analysis increases in IL-12 levels were sampled in the peritoneal fluid cavity, which is the primary tumor microenvironment. Little to no changes were observed in the systemic blood stream of treated patients. In addition, the rise in IL-12 levels was accompanied by local increases in interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), key downstream anti-cancer immune cytokines. Results showed no reports of serious immune-related adverse events including cytokine release syndrome.

"The increases in levels of IL-12 and positive downstream effects on IFN-γ and TNF-α indicate that IMNN-001 treatment is having a broad impact on important cancer-fighting cytokines and effectively targeting the tumor microenvironment with limited to no systemic toxicities," said Premal H. Thaker, M.D., Interim Chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, and the OVATION 2 Study Chair. "I look forward to hopefully seeing these remarkable results from the OVATION 2 Study replicated in a Phase 3 trial, which would further validate the significant potential of IMNN-001 to be transformative for the current standard of care for women with newly diagnosed advanced ovarian cancer."

In December 2024, IMUNON reported continued strong improvement in overall survival data from the Phase 2 OVATION 2 Study, demonstrating an improvement in median overall survival of 13 months following treatment with IMNN-001 (100 mg/m2) plus SoC NACT compared to SoC alone. More than one-third of patients in the trial survived more than 36 months from the point of study enrollment, with 62% of those surviving patients from the IMNN-001 treatment arm and 38% from the SoC arm. More than 10% of trial participants have reached 48 months or beyond.

Also in December 2024, IMUNON announced the outcome of an End-of-Phase 2 in-person meeting with the U.S. Food and Drug Administration (FDA), supporting the advancement of IMNN-001 for the treatment of advanced ovarian cancer into a Phase 3 pivotal study. IMUNON remains on track to initiate a Phase 3 pivotal trial of IMNN-001 using the selected 100 mg/m2 dose in the first quarter of 2025.

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare NACT plus IMNN-001 versus standard-of-care NACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to NACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. IMUNON previously reported positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin compared to standard-of-care NACT alone in 112 patients with newly diagnosed advanced ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On February 19, 2025 Photocure ASA (OSE:PHO) reported Hexvix/Cysview revenues of NOK 128.6 million in the fourth quarter of 2024 (Q4 2023: NOK 114.2 million) and EBITDA of NOK 8.5 million (NOK 29.9 million) (Press release, PhotoCure, FEB 19, 2025, View Source [SID1234650394]). Photocure expects product revenue growth in the range of 7% to 11% and year-over-year EBITDA improvement in 2025. While the company is not providing a specific EBITDA guidance range, Photocure expects continued operating leverage flow-through in its core commercial business and significant growth in milestones this year.

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"We delivered strong performance in the fourth quarter of 2024 with 13% growth in Hexvix/Cysview revenue, 11% unit sales growth, and EBITDA of NOK 8.5 million. For the full-year 2024, we grew product revenue by 10% and generated EBITDA of NOK 49.2 million. We continue to execute on growing our Hexvix/Cysview business and have consistently produced positive EBITDA over the last 7 quarters," says Dan Schneider, President & Chief Executive Officer of Photocure.

Photocure reported total group revenues of NOK 141.7 million in the fourth quarter of 2024 (NOK 142.5 million), and EBITDA* of NOK 8.5 million (Q4 2023: NOK 29.9 million), while Hexvix/Cysview revenues grew to NOK 128.6 million in the quarter (NOK 114.2 million). The EBIT was NOK 1.2 million (NOK 22.5 million) and the cash balance at the end of the period was NOK 293.8 million (NOK 259.5 million).

At the end of the fourth quarter of 2024, the installed base of rigid blue light cystoscopy (BLC) systems in the U.S. was 390, up 11% since the same period in 2023. This includes 18 ForTec Medical mobile towers. Photocure estimates that 25 flexible BLC towers remain in the U.S. market.

During the quarter, Olympus launched its high-definition blue light cystoscopy upgrade for its state-of-the-art Viscera Elite III endoscopic platform, which Photocure believes will increase the use of Hexvix in certain Nordic countries and elsewhere in Europe. Also, subsequently in February, Photocure provided an update from its collaboration with Richard Wolf disclosing that a flexible BLC interim solution is now available in Europe.

"We remain focused on the growth of our business and investing in opportunities that can take Photocure to the next level in 2025. Supporting our expected growth this year, our U.S. business is performing well as we continue to increase the base of active accounts using BLC, and mobile tower adoption is anticipated to outweigh remaining declines in flexible BLC usage. New therapeutics entering the market to treat NMIBC** are expected to continue raising the awareness of precision bladder cancer management and emphasizing the importance of better detection with BLC and Hexvix/Cysview. Additionally, the launch of Olympus’ upgraded BLC equipment in Europe is now underway, and our partnership with Richard Wolf is progressing well with a flexible BLC interim solution available sooner than expected," Schneider adds.

Photocure believes that the benefits of Blue Light Cystoscopy with Hexvix/Cysview offering superior detection and management of bladder cancer will continue to be adopted and become the standard of care. Photocure expects product revenue growth in the range of 7% to 11% and YoY EBITDA improvement in 2025. While the Company is not providing a specific EBITDA guidance range, Photocure expects continued operating leverage flow-through in its core commercial business and significant growth in milestones this year.

"We reported our strongest revenue ever in Q4 2024, and our full year revenue and EBITDA results demonstrate Photocure’s ability to execute through headwinds, generate growth and create significant opportunities for the Company," Schneider concludes.

Please find the full financial report and presentation enclosed.

EBITDA* and other alternative performance measures (APMs) are defined and reconciled to the IFRS financial statements as a part of the APM section of the fourth quarter 2024 financial report on page 23.

The quarterly report and presentation will be published at 08:00 CEST and will be publicly available at www.photocure.com. Dan Schneider, CEO and Erik Dahl, CFO, will host a live webcast at 14:00 CET.

The presentation will be held in English and questions can be submitted throughout the event. The streaming event is available through https://channel.royalcast.com/landingpage/hegnarmedia/20250219_4/

The presentation is scheduled to conclude at 14:45 CET.