On December 11, 2023 Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH) ("Shuttle Pharma") reported submission of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to support the next phase of development of Ropidoxuridine (Press release, Shuttle Pharmaceuticals, DEC 11, 2023, View Source [SID1234638462]). Ropidoxuridine is Shuttle Pharma’s lead radiation sensitizer candidate for use in combination with radiation therapy (RT) to treat brain tumors (glioblastoma), a deadly malignancy of the brain with no known cure.

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RT is a proven modality for treating cancers. However, there is a significant need in the market to make radiation more effective. By developing radiation sensitizers, Shuttle Pharma aims to increase cancer cure rates, prolong patient survival and improve quality of life when used as a primary treatment, or in combination with surgery, chemotherapy and immunotherapy.

"Today’s announcement is an important milestone for Shuttle Pharma and the thousands of patients with brain tumors who currently lack effective therapies," stated Shuttle Pharma’s Chairman and CEO, Anatoly Dritschilo, M.D. "The IND submission is the culmination of many years of clinical development by the Shuttle Pharma team, as well as support from the broader cancer community, including the National Institutes of Health’s National Cancer Institute and Small Business Innovation Research program, who have provided guidance and grant funding to bring this potentially important new radiation sensitizing therapy to market."

An IND submission is a request submitted to the regulatory authorities seeking permission to test a new drug or therapeutic substance in humans. The submission includes detailed information about the drug, its composition, pharmacology, toxicology data from preclinical studies, proposed clinical trial protocols, and information on manufacturing and quality control. With the IND application submission now complete, the FDA is expected to provide Shuttle Pharma with its decision to proceed with the Phase II trial within approximately 30 days.

The submission of the IND follows recent receipt of written responses to questions submitted for a Type B pre-Investigational New Drug Application (PIND) meeting with the FDA in September 2023. During the PIND meeting, the FDA provided positive feedback and guidance on the Company’s Chemistry, Manufacturing, and Controls (CMC) and clinical protocol design for Ropidoxuridine, thus providing the pathway to this IND submission.

The planned Phase II trial will investigate whether a new treatment, Ropidoxuridine, taken during radiation treatment, will be a safe and possibly effective for treatment of patients with newly diagnosed IDH-wildtype glioblastoma with unmethylated MGMT promoter.

Dr. Dritschilo added, "Our mission is to improve the lives of cancer patients by developing therapies that are designed to maximize the effectiveness of RT while limiting the side effects of radiation in cancer treatment. This IND submission is an important next step in making this mission a reality."

An estimated 800,000 patients in the US are treated with radiation therapy for their cancers yearly. According to the American Cancer Society and the American Society of Radiation Oncologists, about 50% are treated for curative purposes and the balance for therapeutic care. The market opportunity for radiation sensitizers lies with the 400,000 patients treated for curative purposes, with this number expected to grow by more than 22% over the next five years.

Shuttle Pharma has received Orphan Drug Designation from the FDA, providing potential marketing exclusivity upon first FDA approval for the disease.

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

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.

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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.

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]).

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"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.

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.

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"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].