On October 17, 2024 Shenzhen Chipscreen Biosciences Co., Ltd. (Chipscreen Biosciences, Stock Symbol: 688321.SH) reported to have submitted the company’s Investigational New Drug (IND) application for CS231295 tablets, a Class 1 innovative drug for the treatment of tumors (Press release, Shenzhen Chipscreen Biosciences, OCT 17, 2024, View Source [SID1234647255]). The application has been accepted by the Center for Drug Evaluation of National Medical Products Administration of China (Application Number: CXHL2401105, CXHL2401107, CXHL2401108).

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!

Malignant tumors are one of the main causes leading to human death. Although clinical treatments have been significantly improved, most tumors are still incurable. The drug resistance, tumor recurrence and metastasis still are the biggest threat to long-term survival of patients. Particularly, Malignant brain tumors and brain metastasis not only brings direct life hazards but also has a natural barrier for drug efficacy due to the blood-brain barrier. Therefore, developing new anti-tumor drugs with good brain permeability has become a hot and difficult topic in improving the current tumor therapy.

CS231295 is a novel brain-penetrating small-molecule, multi-target protein kinase inhibitor independently developed by Chipscreen Biosciences, with proprietary intellectual property rights. This drug candidate exhibits significant synthetic lethal effects on tumors carrying particular genetic defects, providing a new treatment option for patients with such tumors. Additionally, it demonstrates potent anti-tumor angiogenesis activity, resulting in broad-spectrum anti-tumor efficacy. In the future, CS231295, either as a monotherapy or in combination with other anti-tumor drugs, is expected to offer differentiated and innovative treatment options for various types of cancer. Due to its excellent blood-brain barrier permeability, CS231295 possesses significant therapeutic advantages for Malignant brain tumors and metastatic brain tumors, with particularly strong potential for treating primary and metastatic brain tumors. In preclinical studies, CS231295 has shown significant pharmacodynamic activity, favorable pharmacokinetic properties, and a good safety profile.

On October 17, 2024 Nektar Therapeutics (Nasdaq: NKTR) reported the publication of the first clinical data from a Phase 1 study evaluating NKTR-255 in combination with an autologous bispecific chimeric antigen receptor (CAR)-T cell therapy targeting CD19 and CD22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in Blood, the peer-reviewed medical journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Nektar Therapeutics, OCT 17, 2024, View Source [SID1234647254]).

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!

NKTR-255 is a novel IL-15 receptor agonist currently being studied in clinical trials in combination with cellular therapies and immune checkpoint inhibitors. NKTR-255 has shown in previous clinical studies that it can proliferate a range of immune cells and augment lymphocyte trafficking.1,2

The data published in Blood showed favorable efficacy with eight out of nine patients (89%) whom successfully received CAR19-22 followed by NKTR-255 achieving measurable residual disease (MRD) negative remission. The study further demonstrated that, at 12 months, relapse-free/progression-free survival for NKTR-255 in combination with the CD19-22 CAR-T cell therapy was double that of historical controls (67% vs 38%).

"We are encouraged by these first clinical data that clearly demonstrate the ability of NKTR-255 to potentiate CAR-T cell therapy," said Mary Tagliaferri, MD, Senior Vice President and Chief Medical Officer at Nektar. "Data showed NKTR-255 in combination with CD19-22 CAR-T cell therapy resulted in a 67% 12-month relapse-free survival rate in relapsed or refractory B-ALL and investigators observed significant increases in proinflammatory cytokines and chemokines which suggest lymphocyte trafficking to tissues."

The Phase 1 single-center, single-arm dose-escalation study was conducted by Stanford Medicine and evaluated NKTR-255 in combination with CD19-22 CAR-T cell therapy in patients with relapsed or refractory B-ALL (NCT03233854).

"While CAR-T cell therapies have transformed the treatment landscape for B-cell malignancies, there remains a significant unmet need to drive durable treatment outcomes as relapse occurs in the majority of patients," said David Miklos, MD, Chief of BMT and Cell Therapy Program at Stanford Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy.

The primary outcomes of this study were feasibility and safety. Secondary endpoints were assessed for patients who received NKTR-255 (n=9) and included pharmacokinetics of NKTR-255 as measured by IL-15 levels in blood and efficacy as measured by remission free survival (RFS). Exploratory endpoints included cytokine profiling, CAR19-22 expansion in blood, bone marrow, and cerebrospinal fluid (CSF), and long-term CAR-T persistence.

Key findings are summarized below:

No dose-limiting toxicities related to NKTR-255 were observed. The most common adverse events in patients receiving NKTR-255 in combination with the CD19-22 CAR-T cell therapy were fevers, chills, and myelosuppression, which were either self-limiting or manageable with supportive care. The toxicities observed with the combination treatment were similar to those seen after CD19-22 CAR-T cell therapy alone.
Cytokine and chemokine profiling showed significant increases in IL-15 levels. Increase in CXCL9 and CXCL10 were associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood, and ten-fold increases CAR-T cells in CSF, suggesting lymphocyte trafficking to tissue.
Favorable efficacy was observed in patients with relapsed or refractory B-ALL treated with NKTR-255 in combination with CD19-22 CAR-T. Eight out of nine patients achieved complete remission with or without hematologic recovery, all without detectable MRD.
Compared to Stanford’s control group previously treated with the CD19-22 CAR-T cell therapy, NKTR-255 when added to the cell therapy increased the 12-month relapse free survival from 38% to 67%. The median RFS for the CAR T cell only cohort was 3.9 months. For the cohort treated with NKTR-255 and the CD 19-22 CAR-T cell therapy, the median RFS has not been reached with over 14 months of follow up. Only three patients who received combination therapy (33%) relapsed, suggesting administration of NKTR-255 to the CD19-22 CAR-T cell therapy helps prevent early disease recurrence.
The full citation of this article can be accessed here (Volume 144, Issue 16, Pages 1649-1753).

About NKTR-255

NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body’s innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response.

In addition to studies in combination with CAR T cell therapies, NKTR-255 is being studied in a Phase 1 clinical trial sponsored by AbelZeta Pharma, Inc., which is evaluating C-TIL051, a tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant metastatic non-small cell lung cancer (NCT05676749). The JAVELIN Bladder Medley study (NCT05327530), sponsored by Merck KGaA, is also ongoing to evaluate NKTR-255 in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma.(NCT05327530)

On October 17, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune, and rare diseases, reported the nomination of a new development candidate under its collaboration with Roche (Press release, Poseida Therapeutics, OCT 17, 2024, View Source [SID1234647253]). The nomination triggered a $15 million milestone payment from Roche to Poseida.

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 new candidate is an allogeneic, dual CAR-T therapy targeting known antigens expressed in hematologic malignancies, including multiple myeloma. The large capacity of Poseida’s non-viral transposon-based DNA delivery system enables the insertion of genes for two full length chimeric antigen receptors (CARs) into T stem cell memory cells (TSCM).

"The nomination of a new development candidate builds on our collaboration with Roche and highlights the unique potential of our proprietary non-viral genetic engineering toolkit to create differentiated, TSCM-rich allogeneic CAR-T therapies targeting one or more antigens," said Kristin Yarema, Ph.D., president and chief executive officer of Poseida Therapeutics. "Multiple myeloma is a common and incurable blood cancer with significant room for potent, safe and accessible novel agents to expand use across lines of therapy and sites of care. With compelling preclinical data supporting the target combination of this dual CAR-T, we look forward to advancing this program towards the clinic as a part of the collaboration. We also look forward to providing updates on our CAR-T programs and earlier-stage pipeline at Poseida’s upcoming Cell Therapy R&D Day."

Poseida and Roche now have three programs under their collaboration, which was established in August 2022 to develop allogeneic CAR-T therapies directed to hematologic malignancies. The lead collaboration program, P-BCMA-ALLO1, is an allogeneic CAR-T therapy targeting BCMA that has received Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies. Poseida is currently enrolling patients in a Phase 1b portion of the clinical trial. The second program, P-CD19CD20-ALLO1, is an allogeneic dual CAR-T candidate in Phase 1 development for B-cell malignancies.

Dr. Yarema added, "Based on P-BCMA-ALLO1’s promising differentiated safety and efficacy results established with the recent interim Phase 1 data presented at the IMS Annual Meeting in September and in collaboration with Roche, we look forward to continued patient enrollment in the Phase 1b trial. The new allogeneic dual CAR-T therapy candidate announced today will leverage the same proprietary Poseida GMP manufacturing platform that was used to create and advance P-BCMA-ALLO1."

Poseida Cell Therapy R&D Day
The Company plans to host its Cell Therapy R&D Day on November 14th, 2024, featuring presentations from management and top scientists. The event will highlight the Company’s progress across its clinical-stage and earlier-stage pipeline of differentiated allogeneic CAR-T therapies in oncology and autoimmune disease.

The virtual event and access to the live webcast will be available through the following registration link: View Source Registration for this virtual event and access to a replay of the live webcast will also be available on the Investors & Media section of www.poseida.com. A replay of the webcast will be available for approximately 90 days following the presentation.

Cash Position
As of June 30, 2024, the Company’s cash, cash equivalents and short-term investments balance was $237.8 million. With the $15 million milestone from Roche’s nomination of a new development candidate, the Company expects that its cash, cash equivalents and short-term investments together with other remaining near-term milestones and other payments from Roche will be sufficient to fund operations into early 2026. Potential additional anticipated progress and payments under the Roche Collaboration Agreement and/or potential additional business development could further extend the cash runway.

On October 17, 2024 Factor Bioscience Inc. ("Factor") and Eterna Therapeutics Inc. ("Eterna") reported an exclusive license and collaboration agreement aimed at accelerating the development of advanced cell therapy candidates for oncology, rare diseases, and autoimmune disorders (Press release, Factor Bioscience, OCT 17, 2024, View Source [SID1234647252]). Under the terms of the agreement, Eterna has secured a worldwide, exclusive, non-transferable, royalty-bearing license, with the right to grant sublicenses, to develop and market certain induced pluripotent stem cell (iPSC)-based cell therapy products (in particular iPSC derived mesenchymal stem cells (iMSC) that are engineered to express certain cytokines) utilizing Factor’s cell reprogramming and gene-editing technologies, patents, and know-how. The agreement positions both companies with the potential to accelerate the development of advanced cell therapies in the oncology, rare disease, and autoimmune fields.

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!

"We are excited to collaborate with Factor to unlock the full potential of these transformative cell therapies," said Sanjeev Luther, Eterna’s President & CEO. "Our focus at Eterna has always been on developing transformative treatments for patients with difficult-to-treat diseases, and we believe this collaboration agreement increases our potential to rapidly advance therapies that target solid tumors, rare diseases, and autoimmune disorders."

Factor and Eterna will collaborate on data generation that seeks to demonstrate efficacy of the licensed drug candidates for development towards IND by Eterna directly or with third-party sublicensees. As part of the agreement, Factor is entitled to receive milestone payments per product candidate, as well as post-commercialization royalties.

"We are thrilled to support Eterna’s pipeline of advanced cell therapy product candidates," said Matt Angel, Ph.D., CEO of Factor. "Eterna’s team has deep translational and development expertise, making them the ideal partner to develop these products. Together, we are taking an important step toward making these therapies available to patients in need."

On October 17, 2024 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for hematologic malignancies and solid tumors, reported that the South Korean Ministry of Food and Drug Safety (MFDS) has approved a supplemental New Drug Application (sNDA) for XPOVIO (selinexor) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy (Press release, Antengene, OCT 17, 2024, View Source [SID1234647251]).

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!

Prior to the recent approval, XPOVIO has been approved for two indications in South Korea that are: in combination with dexamethasone for the treatment of adult patients with relapsed or refractory MM (R/R MM); and as a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). In July 2024, XPOVIO was included into the reimbursement drug list in South Korea, thus became the first XPO1 inhibitor approved for public insurance coverage in the country.

With a novel mechanism of action, XPOVIO is the world’s first approved orally-available, selective XPO1 inhibitor, which has already been approved in nine countries and regions in APAC and included in the national insurance schemes in South Korea, the mainland of China, Australia, and Singapore. This recent approval for XPOVIO in South Korea will bring another innovative therapy to the clinical management of MM patients in South Korea, benefiting countless patients and families.

While bringing XPOVIO to more APAC markets, Antengene is also striving to expand the indications of XPOVIO. Leveraging the drug’s novel mechanism of action, Antengene is currently developing multiple combination regimens of XPOVIO for the treatment of various indications including myelofibrosis (MF), and endometrial cancer.

About XPOVIO (selinexor)

XPOVIO is the world’s first approved orally-available, selective inhibitor of the nuclear export protein XPO1. It offers a novel mechanism of action, synergistic effects in combination regimens, fast onset of action, and durable responses.

By blocking the nuclear export protein XPO1, XPOVIO can promote the intranuclear accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. XPOVIO delivers its antitumor effects through three mechanistic pathways: 1) exerting antitumor effects by inducing the intranuclear accumulation of tumor suppressor proteins; 2) reducing the level of oncogenic proteins in the cytoplasm by inducing the intranuclear accumulation of oncogenic mRNAs; 3) restoring hormone sensitivity by activating the glucocorticoid receptors (GR) pathway. To utilize its unique mechanism of actions, XPOVIO is being evaluated for use in multiple combination regimens in a range of indications. At present, Antengene is conducting multiple clinical studies of XPOVIO in the mainland of China for the treatment of relapsed/refractory hematologic malignancies and solid tumors (3 of these studies are being jointly conducted by Antengene and Karyopharm Therapeutics Inc. [Nasdaq:KPTI]).