On July 16, 2024 Full-Life Technologies ("Full-Life"), a fully integrated global radiotherapeutics company, reported that it has entered into a license agreement with SK Biopharmaceuticals, a global biotech company, for exclusive worldwide clinical research, development, manufacturing, and commercialization rights to Full-Life’s "FL-091" radiopharmaceutical compound targeting neurotensin receptor 1 (NTSR1) positive cancers (Press release, Full-Life Technologies, JUL 16, 2024, View Source [SID1234644896]).

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This licensing deal worth $571.5 million includes an upfront payment, and development and commercial milestones, separate from royalties. Under the terms of the agreement, SK Biopharmaceuticals will in-license the NTSR1-targeting Radionuclide Drug Conjugate (RDC) program FL-091 – as well as its back-up compounds – aimed at developing and commercializing it as an innovative anti-cancer drug.

FL-091 is a small-molecule radioligand vector designed to deliver targeted radiation therapy to cancer cells by binding specifically to NTSR1, a receptor protein, which is selectively overexpressed in various types of solid tumors, including colorectal cancer, prostate cancer, and pancreatic cancer.

SK Biopharmaceuticals also has a right of first negotiation to license other pre-selected RDC programs of Full-Life.

Lanny Sun, Chief Executive Officer of Full-Life, said, "This agreement with SK Biopharmaceuticals highlights the potential of FL-091 in advancing cancer treatment and demonstrates SK Biopharmaceuticals’ unwavering commitment to building an oncology business around medical innovation. We look forward to future collaborations with SK Biopharmaceuticals, and to leveraging its expertise and resources to advance radiopharmaceutical therapy. The agreement is aligned with our strategic vision of fostering global partnerships and making a meaningful impact on patients worldwide."

Donghoon Lee, Chief Executive Officer and President of SK Biopharmaceuticals, said, "The licensing agreement with Full-Life not only brings the two companies closer together for future collaborations in the fastest rising biotech sector, but also most importantly, pushes SK Biopharmaceuticals forward to become a ‘Big Biotech’. Since the introduction of the company’s strategy roadmap to venture into radiopharmaceuticals last year, we have been on track toward our envisioned goal. We expect to further unveil and implement business plans for RPT (radiopharmaceutical therapy) this year, and actively pursue clinical development and commercialization in the near future to provide treatment options and create new value worldwide."

About FL-091

FL-091 is a novel small-molecule radioligand vector targeting NTSR1 positive solid tumors. Overexpression of NTSR1 has been associated with disease progression of multiple types of cancers, including colorectal, breast, pancreatic, and head and neck cancers. FL-091 radioligands have demonstrated favorable biodistribution profiles and enhanced binding affinity to NTSR1, as well as encouraging anti-tumor activities in preclinical studies. The development of the alpha-emitter therapy candidate 225Ac-FL-091 targeting NTSR1-positive tumors is currently in progress.

On July 15, 2024 Sumitomo Pharma America, Inc. (SMPA) reported that the U.S. Food and Drug Administration (FDA) granted Fast Track designation to DSP-5336 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with a KMT2A rearrangement, also known as, mixed lineage leukemia rearrangement (MLLr) or nucleophosmin mutation (NPM1m) (Press release, Sumitomo Dainippon Pharma, JUL 15, 2024, View Source [SID1234644876]). DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction, which plays key roles in gene expression and protein interactions involved in many biological pathways, including cell growth, cell cycle, genomic stability, and hematopoiesis.1,2,3

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FDA Fast Track Designation is granted to investigational therapies being developed to treat serious or life-threatening conditions that demonstrate the potential to address unmet medical needs.

"For patients and families facing a diagnosis of relapsed or refractory acute myeloid leukemia, significant unmet medical needs remain – and we share in their urgency to identify and advance new treatment pathways," said Tsutomu Nakagawa, Ph.D, President and Chief Executive Officer of SMPA. "We are encouraged by FDA’s decision and look forward to working closely with the agency as we continue our clinical development of DSP-5336."

Updated data from the ongoing open-label, dose escalation and optimization portion of the Phase 1/2 study for DSP-5336 were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress, building on preliminary data presented at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Objective response was observed in 57% (12/21) of patients, which included responses in patients with both Nucleophosmin 1 (NPM1) mutation and KMT2A (MLL) rearrangement. The proportion with complete remission or complete remission with partial hematologic recovery (CR/CRh) was 24% (5/21 patients).

To date, DSP-5336 remains well-tolerated with no dose limiting toxicity (DLT) observed and no significant cardiac signal nor treatment-related discontinuations or deaths. No significant drug-drug interactions with azoles have been identified and repeat dosing results in minimal to no pharmacokinetic accumulation. Importantly, no differentiation syndrome (DS) prophylaxis was needed, and the three cases of DS reported (5%) were manageable and did not result in intensive care unit (ICU) stays or discontinuation of DSP-5336.

"Management of AML continues to be challenging with limited options for which there are currently no approved targeted therapies to treat AML with KMT2A (MLL) rearrangements or NPM1 mutations, leaving a serious unmet medical need," said Jatin Shah, M.D., Chief Medical Officer – Oncology at SMPA. "DSP-5336 has shown promising clinical activity, and menin inhibitors have tremendous potential to impact the outcomes of these types of acute leukemia. We are excited by these early results and FDA Fast Track Designation, and look forward to working closely with the agency and our collaborators to rapidly advance this program with the goal of providing a well-tolerated and effective targeted treatment option for patients with relapsed or refractory acute myeloid leukemia."

Leukemia is a type of cancer that forms in blood-forming tissue, characterized by the uncontrolled growth of blood cells, usually white blood cells, in the bone marrow. Acute leukemia, a form of leukemia, requires immediate treatment as blood cells multiply rapidly leading to a sudden onset of symptoms.4 Approximately 30% of AML patients have NPM1 mutations6 and 5-10% of AML patients have KMT2A (MLL) rearrangements.5

About DSP-5336
DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction. Menin is a scaffold nuclear protein which plays key roles in gene expression and protein interactions involved in many biological pathways, including cell growth, cell cycle, genomic stability, and hematopoiesis.1,2 In preclinical studies, DSP-5336 has shown selective growth inhibition in human acute leukemia cell lines with KMT2A (MLL) rearrangements or NPM1 mutations.1,3 DSP-5336 reduced the expression of the leukemia-associated genes HOXA9 and MEIS1, and increased the expression of the differentiation gene CD11b in human acute leukemia cell lines with MLL rearrangements and NPM1 mutation.7,8 The safety and efficacy of DSP-5336 is currently being clinically evaluated in a Phase 1/2 dose escalation/dose expansion study in patients with relapsed or refractory acute leukemia (NCT04988555). The FDA granted Orphan Drug Designation for DSP-5336 for the indication of acute myeloid leukemia in June 2022. The FDA granted Fast Track Designation for DSP-5336 for the indication of relapsed or refractory acute myeloid leukemia with MLLr or NPM1m in June 2024.

On July 15, 2024 GRAIL, Inc. (NASDAQ: GRAL), a healthcare company whose mission is to detect cancer early when it can be cured, reported an update on the PATHFINDER 2 and NHS-Galleri registrational clinical trials evaluating the Galleri multi-cancer early detection (MCED) test (Press release, Grail, JUL 15, 2024, View Source [SID1234644877]). GRAIL has completed the PATHFINDER 2 study’s planned enrollment of more than 35,000 participants who are eligible for guideline-recommended cancer screening at more than 30 healthcare institutions in North America. In addition, GRAIL has completed the third and final round of study visits for the NHS-Galleri trial, which enrolled more than 140,000 participants.

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"The PATHFINDER 2 and NHS-Galleri studies will significantly expand our existing clinical validation and performance evidence for the Galleri test. By supplementing our robust clinical evidence program with more than 35,000 participants in the U.S. for PATHFINDER 2 and over 140,000 participants in England for NHS-Galleri, we will continue our generation of additional performance, safety, and clinical utility data," said Bob Ragusa, Chief Executive Officer at GRAIL. "Both studies were designed to enroll a diverse participant population, representative of socio-economic, ethnicity, gender and age differences, and we are proud of the diversity of the study populations. The data from these studies, as well as supplemental data from our other clinical studies, will support our premarket approval application submission for Galleri to the FDA, which is currently in process with a modular submission under a Breakthrough Device Designation from the FDA. We look forward to seeing results from the first 25,000 individuals enrolled in the PATHFINDER 2 study in the second half of 2025 and final results from the NHS-Galleri trial in 2026."

About the PATHFINDER 2 Study (NCT05155605)
PATHFINDER 2 is a prospective, multi-center, interventional study evaluating the safety and performance of Galleri in a population of individuals aged 50 years and older who are eligible for guideline-recommended cancer screening in the United States. PATHFINDER 2 is being conducted pursuant to an FDA-approved investigational device exemption (IDE) application and began enrolling in December 2021. The primary objectives of the study are 1) to evaluate the safety and effectiveness of GRAIL’s MCED test based on the number and type of diagnostic evaluations performed in participants who receive a cancer signal detected test result, and 2) to evaluate the performance of GRAIL’s MCED test across various measures, including positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and cancer signal origin (CSO) prediction accuracy. Participants who receive a cancer signal detected result undergo additional diagnostic testing based on the predicted CSO to determine if a cancer is present. Secondary objectives include utilization of guideline-recommended cancer screening procedures after use of the MCED test, and participant reported outcomes (PRO) over several time points, including an assessment of participants’ anxiety and satisfaction with the MCED test. Timepoints for collection will include baseline measurement prior to testing, post-results, and post-diagnostic resolution for positive test results.

The PATHFINDER 2 study is being conducted with leading healthcare institutions across the United States, including Cleveland Clinic, Duke University Health System, Flushing Hospital Medical Center, Henry Ford Health System, Hoag, Inova, Jamaica Hospital Medical Center, Kelsey-Seybold Clinic, Mayo Clinic, Morehouse School of Medicine, Ochsner Health, Oregon Health & Science University, Sarah Cannon, Sutter Health, University of Oklahoma, University of Pittsburgh, Virginia Commonwealth University, Weill Cornell Medicine, and others.

About the NHS-Galleri Trial (NCT05611632)
In 2020, NHS England selected GRAIL to assist with the United Kingdom’s ambitions for early cancer detection and to assess Galleri for potential population screening on a national scale. In 2021, we initiated the NHS-Galleri trial, a fully enrolled prospective randomized controlled clinical utility trial of over 140,000 participants between the ages of 50 and 77 at the time of enrollment, to evaluate the implementation of Galleri alongside the existing NHS standard of care screenings. The primary objective of the trial is to assess whether implementation of Galleri can reduce the incidence of late-stage cancers through early cancer detection. The trial aimed to enroll a representative population sample to promote health equity and was fully enrolled in just over 10 months.

The trial is designed for participants to provide three blood draws over a two-year period, with the first draw taken at enrollment. As a randomized controlled trial, half of the trial participants have received the Galleri test, and half have had their blood sample stored for future analysis. Any participant in the interventional arm with a cancer signal detected result has been referred for further diagnostic workup within the NHS. All other participants and their physicians remain blinded as to which arm of the study they are in. The NHS-Galleri trial design was published in Cancers in 2022.

Collaborators include Queen Mary University of London, King’s College London Cancer Prevention Trials Unit, and NHS England.

On July 15, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that data published in the journal Cell demonstrate that neoadjuvant monotherapy with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib results in a high response rate and reshapes the tumor microenvironment (TME), providing new targets for immunotherapy and combination regimens in patients with homologous recombination deficiency (HRD) positive ovarian cancer (Press release, Zai Laboratory, JUL 15, 2024, View Source [SID1234644879]). The study revealed niraparib preferentially suppresses certain immune cells that support the growth of HRD-positive ovarian tumors.

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This Zai Lab-supported study also showed that targeted clearance of infiltrating regulatory T cells (eTregs) using Zai Lab’s investigational CCR8 antibody, ZL-1218, significantly sensitized niraparib against HRD tumors, resulting in decreased tumor burden in pre-clinical models.

"Given the prevalence of HRD in cancer and its role in rendering tumors vulnerable to PARP inhibition, this study fills the knowledge gap regarding the impact of HRD and related therapies on the tumor microenvironment," said Professor Qinglei Gao, Chief of Gynecologic Oncology Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. "By decoding the tumor-reactive T cells in the HRD-positive TME that are regulated by eTregs, these findings have profound implications for future oncology research and therapeutic development for HRD-positive ovarian cancer and other HRD-related cancers."

To investigate the effects of HRD, neoadjuvant therapies, and their interactions on the TME, investigators utilized tumor tissues from a clinical study (NCT04507841) evaluating niraparib for the neoadjuvant treatment of unresectable ovarian cancer. In parallel, tissue samples from patients receiving neoadjuvant chemotherapy (NACT) were also collected.

Profiling of these samples yielded valuable data delineating the divergence in TME between HRD-positive vs. homologous recombination-proficient (HRP) tumors, as well as their respective phenotypic evolution following the introduction of neoadjuvant therapies.

Key findings of the study included:

Patients receiving neoadjuvant monotherapy with niraparib achieved 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively.
Overall, the safety profile of NANT was manageable, and no new safety signal was observed, with hematologic toxicities as the most common treatment-related adverse events.
The results indicate that NANT is an effective neoadjuvant treatment option for controlling disease progression in patients with HRD-positive high-grade serous ovarian cancer (HGSOC).
eTregs were identified as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells.
The addition of the CCR8 antibody, ZL-1218, to niraparib showed a significantly pronounced inhibitory effect on eTregs in pre-clinical models, suppressing tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.
"Zai Lab is pleased to support this important translational research which breaks new ground in our understanding of the tumor microenvironment in HRD-positive ovarian cancer," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "By identifying new immunotherapeutic targets in the TME, these findings could bolster efforts to improve outcomes for patients with HRD+ tumors."

On July 15, 2024 GC Cell (KRX: 144510.KS) and Checkpoint Therapeutics ("Checkpoint") (Nasdaq: CKPT) reported a collaboration to explore the combined therapeutic potential of cosibelimab, Checkpoint’s anti-PD-L1 antibody with dual mechanism of action, with GC Cell’s Immuncell-LC, an innovative autologous Cytokine Induced Killer ("CIK") T cell therapy composed of cytotoxic T lymphocytes and natural killer T cells (Press release, Checkpoint Therapeutics, JUL 15, 2024, View Source [SID1234644860]).

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This collaboration will initially focus on conducting in vitro combination studies to evaluate the synergistic effects of these two therapies on cancer cell destruction. Positive preliminary data from these studies could potentially pave the way for future in vivo research and clinical studies.

The anticipated synergy between cosibelimab’s antibody-dependent cellular cytotoxicity ("ADCC") mechanism of action and Immuncell-LC’s robust autologous CIK T cell response is supported by extensive research. This combination is expected to leverage immune system components more effectively in targeting and eliminating cancer cells.

James Park, CEO of GC Cell, highlighted the agreement’s potential: "This collaboration is a pivotal step towards significant technological collaborations. The integration of cosibelimab’s clinical efficacy and safety profile with our Immuncell-LC could set new therapeutic standards in immuno-oncology. We are optimistic that this partnership will lead to effective commercial licensing or joint development in the future."

James F. Oliviero, CEO of Checkpoint Therapeutics, concurred: "Both cosibelimab, with its dual mechanism of action, and Immuncell-LC show great promise as potential immuno-oncologic therapies. We are pleased to work in collaboration with GC Cell to determine if using the two therapies in combination may offer even greater potential benefits than being used singly."

About Immuncell-LC
Immuncell-LC stands as the sole commercially approved adoptive T cell therapy for hepatocellular carcinoma adjuvant treatment. Comprising autologous, significantly expanded CIK (Cytokine Induced Killer) T lymphocytes, it has demonstrated proven efficacy in a large-scale Phase 3 clinical trial—reducing the risk of recurrence by 37% and decreasing mortality by 79% compared to the active surveillance group. Administered to over 10,000 patients in South Korea, Immuncell-LC has shown an excellent safety profile without treatment-related serious adverse events.

About Cosibelimab
Cosibelimab is a potential differentiated, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 ("PD-L1") and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained high tumor target occupancy of PD-L1 to reactivate an antitumor immune response and the additional potential benefit of a functional Fc domain capable of inducing ADCC for potential enhanced efficacy.