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First Patient Dosed in U.S. Expanded Access Program for TLX250-CDx, Telix’s Breakthrough Kidney Cancer Imaging Agent

On December 11, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported that the first patient has been dosed in a United States (U.S.) expanded access program (EAP, ClinicalTrials.gov ID: NCT06090331) for TLX250-CDx (89Zr-DFO-girentuximab) (Press release, Telix Pharmaceuticals, DEC 11, 2023, View Source [SID1234638461]). TLX250-CDx is the Company’s first-in-class, non-invasive investigational positron emission tomography (PET) imaging agent in clear cell renal cell carcinoma (ccRCC).

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The patient was dosed at ARA Diagnostic Imaging at Austin Radiological Association in Austin (TX, U.S.) following U.S. Food and Drug Administration (FDA) agreement to proceed.

FDA agreement for an EAP follows the completion of Telix’s successful global Phase III ZIRCON study (Zirconium in Renal Cancer Oncology, ClinicalTrials.gov ID: NCT03849118), which reported positive results in November 2022, meeting all co-primary and secondary endpoints.[1]

Dr John Leahy, molecular radiologist and nuclear medicine specialist at ARA Diagnostic Imaging and a Principal Investigator on the EAP stated, "With TLX250-CDx, for the first time, urologists and urologic oncologists may have a non-invasive way to determine the presence of ccRCC, the most common and aggressive form of kidney cancer. We are therefore extremely pleased to have been selected as the inaugural site for this national EAP, with patients in Austin and the surrounding area now able to benefit from greater confidence in their kidney cancer diagnosis and treatment planning."

Mary Jessel, Senior Vice President of Global Medical Affairs at Telix added: "Ahead of regulatory approval, this EAP provides continued access to TLX250-CDx to address a clear unmet patient need. ZIRCON results demonstrate that TLX250-CDx has potential to become a new standard of care in the diagnosis and staging of ccRCC, where existing imaging can be inconclusive."

Under its EAPs – sometimes called ‘compassionate use’ – the FDA works with companies to allow access to investigational products outside of a clinical trial to patients for whom there are no comparable or satisfactory alternate options.

Telix is progressing towards a Biologics License Application (BLA) submission for TLX250-CDx with the FDA and other equivalent applications with regulatory agencies in key commercial jurisdictions.

U.S. patients, or physicians who may have eligible patients in the U.S., can e-mail [email protected] for further information about the TLX250-CDx EAP.

Telix’s Policy on Offering Compassionate Use to Investigational Medicines can be downloaded at the following link.

For more information about ongoing clinical trials of TLX250-CDx, please visit View Source

Mabwell Announces the CDE Approval of Novel Nectin-4 Targeting ADC for Phase III Clinical Trial

On December 11, 2023 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported that its submission to the Center for Drug Evaluation (CDE) of the National Medical Products Administration for the "A Randomized, Open-label, Controlled, Multicenter Phase III Clinical Trial of 9MW2821 versus Investigator’s Choice of Chemotherapy for Treating Unresectable Locally Advanced or Metastatic Urothelial Carcinoma in Patients Previously Treated with Platinum-Containing Chemotherapy and PD-(L)1 Inhibitors" has been approved (Press release, Mabwell Biotech, DEC 11, 2023, View Source [SID1234638460]). The company will now officially initiate the Phase III clinical study of 9MW2821 for treating locally advanced or metastatic urothelial carcinoma in patients previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors.

9MW2821 is a novel Nectin-4 targeting ADC developed independently by Mabwell, marking the first of its kind among the products developed in China with the same target to enter clinical trials. As of December 5, 2023, more than 250 subjects were enrolled. In the Phase II clinical trial of 9MW2821, at a dose of 1.25 mg/kg, the monotherapy resulted in an objective response rate (ORR) of 62.2% (95% CI: 44.8%–77.5%) and a disease control rate (DCR) of 91.9% (95% CI: 78.1%–98.3%) in patients with advanced urothelial carcinoma. The median progression-free survival (PFS) was 6.7 months (95% CI: 3.8–NR), while the median overall survival (OS) has not been reached yet.

Currently, multiple clinical trials are being conducted simultaneously for this project. Clinical trials on combination therapy with other treatments, in addition to monotherapy, are also advancing. Promising antitumor activity coupled with favorable safety profiles has been observed across various cancer types.

About Urothelial Carcinoma
According to the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), bladder cancer is the ninth most common malignant tumor in terms of incidence and ranks thirteenth in mortality among malignant tumors. According to the 2016 Chinese national cancer statistics published by the National Cancer Center in February 2022, there were 82,300 new bladder cancer cases, with an incidence of 3.53 per 100,000 individuals. Urothelial carcinoma, ranking among the top ten most prevalent cancers in China, is characterized by its tendency toward metastasis and recurrence. Advanced urothelial carcinoma is associated with short survival, contributing to a substantial disease burden in China and seriously compromising patients’ survival and quality of life.

About 9MW2821
9MW2821 is a novel Nectin-4 targeting ADC developed by world-class ADC development platform and automated high-throughput antibody discovery platform of Mabwell. It achieves site-specific modification of antibody through proprietary conjugate technology linkers and optimized ADC conjugation process. 9MW2821 can specifically bind to Nectin-4 on the cell membrane surface, be internalized and release cytotoxic drug, and induce the apoptosis of tumor cells. The company is conducting several clinical trials on a range of indications, including urothelial carcinoma and cervical cancer. Currently, the R&D progress of 9MW2821 ranks first in China and second in the world. 9MW2821 is the first to read out preliminary clinical data in cervical cancer among the products with the same target in the world.

NAYA Biosciences Announces Publication of New Data for its CD38-targeted Flex-NK™ Bispecific Antibody in the American Society of Hematology’s Blood Journal

On December 11, 2023 NAYA Biosciences Inc. ("NAYA"), a company which has recently signed a definitive merger agreement with INVO Bioscience to establish an expanded, publicly-traded life science company dedicated to increasing patient access to breakthrough treatments in fertility, oncology, and regenerative medicine, reported that new data for its CD38-targeted Flex-NK Bispecific Antibody (NY-338, formerly CYT-338) for the treatment of Multiple Myeloma (MM) was published as an abstract in the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) meeting supplement of Blood, in the "Multiple Myeloma: Prospective Therapeutic Trials" section (Press release, NAYA Biosciences, DEC 11, 2023, View Source [SID1234638459]).

"NAYA is building a portfolio of differentiated clinical-stage oncology therapeutics, starting with two FLEX-NK bispecific antibodies acquired from Cytovia Therapeutics," commented NAYA CEO Dr. Daniel Teper. "We are excited about this new data for our CD38-targeted antibody, which aims to address limitations with the current standard-of-care and offer new options for multiple myeloma patients."

"The synergistic engagement of NK cells through NKp46 greatly enhances the immunotherapeutic effects of FLEX-NK bispecific antibodies, reducing NK cell fratricide, maintaining NK cell levels, and enhancing potency including reversal of NK cell dysfunction," added Ola Landgren, MD, PhD, co-author of the abstract and Professor of Medicine, Chief of the Myeloma Division, and Leader of the Experimental Therapeutics Program at the University of Miami’s Sylvester Comprehensive Cancer Center. "The data supports initiation of clinical trials to evaluate this promising new therapy and makes it a potential best-in-class anti-CD38 therapeutic for multiple myeloma."

Despite the clinical success of the first anti-CD38 targeted monoclonal antibody, daratumumab, approved for the treatment of multiple myeloma (MM), significant challenges remain such as CD38 antigen loss/internalization and/or natural killer (NK) cell fratricide resulting in resistance to treatment over time. The data presented for NY-338 demonstrates a differentiated profile from daratumumab, with best-in-class potential, and supports the initiation of clinical trials in 2024. Specifically, the conclusions show that the unique NKp46 activation mechanism provided by NY-338 for reducing NK cell fratricide and maintaining NK cell levels together with the enhanced potency including reversal of NK cell dysfunction makes it an attractive best-in-class anti-CD38 therapeutic against MM compared to daratumumab. These results support the development of CYT-338 in both monotherapy and combination with other complementary immunotherapy agents being developed or approved for MM. A first-in-human Phase 1 study targeting patients with relapsed/refractory MM is in development in the U.S.

Yingli Pharma presents a pivotal Phase 2 study data evaluating linperlisib in relapsed or refractory peripheral T-cell lymphoma in an oral session at the American Society of Hematology 2023 Annual Meeting

On December 11, 2023 Shanghai Yingli Pharmaceutical Co., Ltd. ("Yingli Pharma"), a biopharmaceutical company focused on developing oral therapies for cancer and metabolic diseases, reported the pivotal Phase 2 clinical trial results of the investigation of linperlisib in the treatment of patients with relapsed or refractory (r/r) peripheral T-cell lymphoma (PTCL) (Press release, Yingli Pharmaceutical, DEC 11, 2023, View Source [SID1234638458]). Linperlisib is a phosphoinositide 3-kinase delta (PI3Kδ) oral inhibitor, approved in China for treatment of patients with r/r follicular lymphoma after systemic therapy.

"There is a vital need for new therapies to treat highly aggressive cancers such as r/r PTCL where there are very limited treatment options." said Dr. Jun Zhu, Professor, Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China, who was the leading investigator for this pivotal clinical trial. "In addition to the promising efficacy and well manageable safety of linperlisib in r/r PTCL, it is noteworthy that a high proportion of the treated patients were shown to have a complete response, and responses have been seen in all the major PTCL subtypes."

"Our approach is to develop novel oral agents that will allow patients to safely administer at home," said Michael Hui, CEO of Yingli Pharma, "We are delighted that the encouraging results of this study support the use of linperlisib in this hard-to-treat disease and are excited to continue developing linperlisib in more indications. The company has applied for linperlisib marketing approval in r/r PTCL in China based on these pivotal study findings." Mr. Hui added, "We look forward to the results of an ongoing open-label multi-center Phase 2 study in the U.S. and Italy in r/r PTCL and r/r CTCL."

Safe and effective treatment of r/r PTCL patients

The pivotal r/r PTCL Phase 2 clinical trial enrolled 98 patients (pts) from May 2021 to October 2022 at 25 clinical sites in China. The pts had a median of two lines of prior systemic therapies. Sixty-four pts (73%) had refractory disease, 59 pts (67%) had relapsed disease, and 35 pts (40%) had both relapsed and refractory diseases. All patients received linperlisib at 80 mg QD, the RP2D for the drug, with a minimum of 6 months follow-up.

The linperlisib-treated patients (Full Analysis Set N = 88) evaluated by Lugano criteria, had a 48% overall response rate, including 30% complete responses and 18% partial responses, as well as a 68% disease control rate. The median Duration of Response was not reached although the 6-month DOR rate was 75%. The median PFS was 5.5 months (95% CI, 3.5, 15.6) and the median OS was 14.2 months (95%CI, 7.9, not reached). Responses were observed across PTCL subtypes.

Linperlisib was well tolerated with a differentiated and manageable safety profile, specifically having very low levels of immune-mediated toxicities. In the linperlisib-treated patient safety dataset (N=98) for the pivotal study, the most common hematologic treatment related adverse events (TRAEs) of Grade≥3 were neutropenia (32%), leukocytopenia (10%), Anemia (6%), Thrombocytopenia (5%), and Lymphocytopenia (5%). The most common nonhematologic TRAEs of Grade≥3 were pneumonia (14%) and upper respiratory tract infection (5%). Immune-mediated Grade≥3 TRAEs including elevated ALT, AST, diarrhea, colitis, rash were not reported or were <5%. Nine patients (9.2%) discontinued from the study due to various adverse events. The safety results of this study were consistent with previously reported data in other linperlisib clinical studies.

About linperlisib

Linperlisib, a next-generation PI3K-selective oral inhibitor, received marketing approval in China in 2022 for treatment of patients with relapsed and/or refractory follicular lymphoma after two or more systemic therapies. Linperlisib also received U.S. FDA Orphan Drug Designations for follicular lymphoma, chronic lymphocytic leukemia, and T cell lymphomas.

Linperlisib is under investigation in multiple additional clinical trials as a monotherapy: frontline PTCL, r/r large granular T lymphocytic leukemia, r/r autoimmune hemolytic anemia; and in combination with other agents: in second line follicular lymphoma and marginal zone lymphoma, frontline PTCL, and r/r CTCL. In the U.S. and EU, linperlisib is being developed by 280Bio, Inc (San Francisco, CA., USA), a wholly-owned subsidiary of Yingli Pharma, in a Phase 2 clinical study in r/r T Cell Lymphomas [PTCL and CTCL].

Sumitomo Pharma Presents Encouraging New Data on DSP-5336 Clinical Activity at the American Society of Hematology Annual Meeting

On December 11, 2023 Sumitomo Pharma America, Inc. (SMPA) reported new data from the ongoing Phase 1/2 first-in-human study of DSP-5336, in patients with relapsed or refractory acute leukemia, presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, Sumitomo Pharmaceuticals, DEC 11, 2023, View Source [SID1234638457]). DSP-5336 is an investigational small molecule inhibitor of the menin and mixed-lineage leukemia (MLL) protein interaction, which plays key roles in biological pathways, including cell growth regulation, cell cycle control, genomic stability, bone development, and hematopoiesis.1,2,3

Data from the open-label, ongoing dose determination portion of the Phase 1/2 study enrolling patients with relapsed or refractory acute leukemia with relevant genomic alterations receiving oral DSP-5336 up to 200 mg twice-daily were presented at the meeting. In the ongoing study, patients are continuing to dose escalate and are now at therapeutic levels.

Preliminary results presented at ASH (Free ASH Whitepaper) 2023 included four evaluable patients treated with DSP-5336 200 mg twice-daily, three of whom showed objective responses. Clinical remission with partial hematologic recovery and clinical remission with incomplete count recovery (CRh/CRi) was achieved by one patient, CRi was achieved by one patient, and morphologic leukemia-free state (MLFS) was achieved by one patient. All patients cleared peripheral blasts. To date, DSP-5336 has been well-tolerated, notably, with no treatment-related cardiac effects, including QT prolongation. Additionally, differentiation syndrome has not been observed at the 200 mg twice-daily dose.

"While these data are early-stage, it is encouraging to see promising clinical activity from DSP-5336, particularly with limited safety signals and a clean tolerability profile to date," said Navel Daver, M.D., Director, Department of Leukemia, Division of Leukemia Research Alliance Program, The University of Texas MD Anderson Cancer Center and lead author on the DSP-5336 poster at ASH (Free ASH Whitepaper). "DSP-5336 is an investigational targeted therapy that inhibits menin-MLL protein interaction. Inhibition of the menin-MLL protein interaction may be able to reverse the leukemogenic activity of MLL fusion proteins and may be a future therapeutic option for acute 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.4 Acute leukemia, a form of leukemia, requires immediate treatment as blood cells multiply rapidly leading to a sudden onset of symptoms.4

"There is a high unmet need for new and innovative approaches in the treatment of relapsed or refractory acute leukemia, as many patients have limited options to treat the disease or do not respond to currently available cancer therapies," said Jatin Shah, M.D., Chief Oncology Development Officer, SMPA. "We believe we are close to determining the appropriate therapeutic dose of DSP-5336 in our ongoing study and were encouraged by our discussions on these results with the leading hematological oncology community at ASH (Free ASH Whitepaper). We look forward to continuing the study of DSP-5336 as a monotherapy and to exploring additional combination studies."

Additional SMPA data presented at ASH (Free ASH Whitepaper) included an oral presentation of encouraging preliminary results from the ongoing Phase 1/2 study of TP-3654 monotherapy in patients with relapsed or refractory myelofibrosis who were previously treated with or ineligible for a JAK inhibitor.

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 that plays various key roles in biological pathways, including cell growth regulation, cell cycle control, genomic stability, bone development, 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 showed induced reduction of gene expression of HOXA9 and MEIS1, which are highly expressing leukemia associate genes, and increased expression of differentiation marker gene CD11b in the human acute leukemia cell lines with MLL rearrangements.5,6 DSP-5336 also showed growth inhibition and changes of gene expression levels of HOXA9, MEIS1 and CD11b on human acute leukemia patient samples with MLL rearrangements or NPM1 mutations.5,6 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.

About TP-3654
TP-3654 is an oral investigational inhibitor of PIM1 kinase, which has shown potential antitumor and antifibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.7,8 TP-3654 was observed to inhibit proliferation and induce apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2V617F mutation.7 TP-3654 alone and in combination with ruxolitinib showed white blood cell and neutrophil count normalization, and also reduced spleen size and bone marrow fibrosis in JAK2V617F and MPLW515L murine models of myelofibrosis.8 The safety and efficacy of TP-3654 is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate and high-risk myelofibrosis (NCT04176198). The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for TP-3654 for the indication of myelofibrosis in May 2022.