On August 15, 2023 Thryv Therapeutics Inc., a clinical stage biotechnology company developing therapies for rare diseases including Congenital Long QT Syndrome (LQTS), atrial fibrillation, and resistant cancers, reported FDA clearance of its Investigational New Drug application (IND) for THRV-1257 (Press release, Thryve Therapeutics, AUG 15, 2023, View Source [SID1234634435]). THRV-1257 is being investigated for the treatment of advanced Anaplastic Thyroid Cancer (ATC), including those patients with the common BRAF mutation V600E. The first in human study will determine the optimal dosing of THRV-1257 in patients with solid tumors, followed by treatment in combination with approved cancer therapies.

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At the same time, the company announces acceptance of a late breaking poster that will be presented at the upcoming American Thyroid Association (ATA) annual meeting in Washington DC, on September 30th, 2023, from 10:00 a.m. to 1:00 p.m. The presentation will highlight in vitro and in vivo preclinical results of SGK1 inhibition in models of ATC.

"Preclinical evaluation of our SGK1 inhibitors uncovered novel biology and synergy with existing cancer treatments to extend their activity and reverse resistance. These studies have revealed a significant opportunity to intervene in several oncology treatment paradigms with an SGK1 inhibitor" said Eric Campeau, Vice President, Translational Research.

According to the ATA, approximately 64,000 people in the United States are diagnosed with thyroid cancer each year. ATC makes up approximately 2% of these cases. Although ATC is rare compared to other thyroid cancers, it is one of the fastest growing and most aggressive of all cancers. Rapid evaluation and diagnosis are critical for ATC patients, as the disease manifests as a rapidly growing neck mass that impairs speech, swallowing and breathing. Activation of Serine and Glucocorticoid Kinase 1 (SGK1) was determined to be a critical component of ATC cell proliferation, including in tumor cell lines with mutated BRAF. Inhibition of SGK1 was unique in its capacity to suppress ATC cell proliferation compared to other inhibitors tested. Thryv Therapeutics is collaborating with expert scientists and oncologists in ATC to evaluate its SGK1 inhibitors as a potential treatment option to improve the outcome of people with this devastating disease.

"We are excited to advance our portfolio of potent SGK1 inhibitors into the treatment of aggressive, treatment resistant cancers. SGK1 has been implicated in a number of treatment-resistance oncology pathways and our work has demonstrated the potential to delay resistance and restore activity of approved therapies and ultimately improve progression free and overall survival outcomes," said Debra Odink, President, and Chief Development Officer.

On August 15, 2023 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that the U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) and granted Priority Review for TIBSOVO (ivosidenib tablets) in the treatment of patients with isocitrate dehydrogenase 1 (IDH1)-mutated relapsed or refractory (R/R) myelodysplastic syndromes (MDS) (Press release, Servier, AUG 15, 2023, View Source [SID1234634434]). If approved, TIBSOVO would be a first-in-class targeted therapy option for MDS patients within this molecularly defined subset.

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"Servier continues to drive our leadership in the scientific innovation behind targeted mutant IDH inhibition, transforming the treatment landscape for thousands of patients living with difficult and hard-to-treat cancers," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "This filing acceptance and Priority Review for TIBSOVO in patients with relapsed or refractory myelodysplastic syndromes underscores our continued work to advance therapeutic progress across IDH mutated cancers, and if approved in this setting, will bring the first and only targeted therapy to patients living with a significant unmet need."

The sNDA is based on key results from a pivotal Phase 1, open-label study in IDH1-mutated R/R MDS patients, in which TIBSOVO demonstrated durable remissions, including complete response in nearly 40% of patients, and an acceptable safety profile. The updated efficacy results were presented at the 2023 European Hematology Association (EHA) (Free EHA Whitepaper) Congress.

These findings showed that in the efficacy analysis set (n=18), a complete remission (CR) rate of 38.9% and objective response rate (ORR) of 83.3% were documented in patients treated with TIBSOVO. In addition, the median time to CR was 1.87 months (range: 1.0, 5.6). At the time of data cutoff, the median duration of CR had not been reached (range: 1.9, 80.8*) and the median overall survival was 35.7 months (range: 3.7*, 88.7*). Additionally, of the nine patients who were transfusion dependent with red blood cells or platelets at baseline, 66.7% (n=6) became independent of transfusions during any ≥56-day post-baseline period. Overall, treatment-related adverse events were consistent with the known safety profile of TIBSOVO. There were no new safety signals identified in this study.

"While the novel use of targeted IDH inhibition has been proven across a number of difficult-to-treat cancers, there continues to be a significant unmet need for MDS patients within this molecularly defined subset, especially for those who experience disease progression," said Amir Fathi, M.D., Program Director, Center for Leukemia at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. "Today’s filing acceptance provides further support for the potential efficacy and acceptable safety profile of TIBSOVO in relapsed or refractory MDS and reinforces the importance of mutational testing in this patient population."

Priority Review is granted to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions.1

FDA Breakthrough Therapy designation was previously granted for TIBSOVO for the treatment of adult patients with R/R MDS with a susceptible IDH1 mutation as detected by an FDA-approved test.

* Denotes a censored observation.

About the NCT02074839 Clinical Trial2
This Phase I, open-label multinational study evaluated the safety, tolerability, and clinical activity of ivosidenib in patients with relapsed or refractory myelodysplastic syndromes with an IDH1 mutation. The primary endpoint was complete remission (CR) plus partial remission (PR) rate and key secondary endpoints included duration of CR plus PR, duration of transfusion independence, and time to transfusion independence.

About TIBSOVO (ivosidenib tablets)
TIBSOVO is currently approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory AML and in monotherapy or in combination with azacitidine for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. TIBSOVO was recently approved by the European Commission as a targeted therapy in two indications: in combination with azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy; as well as in monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy. TIBSOVO has also been approved in the U.S. and Australia for patients with previously treated IDH1-mutated cholangiocarcinoma. TIBSOVO is also approved in China for the treatment of adult patients with relapsed or refractory AML who have a susceptible IDH1 mutation. Servier has granted CStone a co-exclusive license for the development and an exclusive license agreement for the commercialization of TIBSOVO in Mainland China, Taiwan, Hong Kong, Macao and Singapore.

About Myelodysplastic Syndromes
Myelodysplastic Syndromes (MDS) are disorders in which progenitor (stem) cells do not mature into healthy blood cells.3 In the U.S., approximately 16,000 new cases of MDS are reported each year,4 and one-third of those MDS patients will eventually progress to acute myeloid leukemia (AML).3 Approximately 3.6% of MDS patients have an IDH1 mutation, which have often been associated with worse overall outcomes and are considered early "driver" mutations in the progression of MDS to AML.5,6 Chemotherapy, supportive therapy, stem cell transplant, growth factors and similar medicines are used to treat MDS.

On August 15, 2023 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported that it is going to present three posters highlighting study results from ongoing trials related to Osemitamab (TST001) at the 2023 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress including updated efficacy and PK/PD analysis data from the phase 2 study of Osemitamab (TST001)/CAPOX in CLDN18.2 positive first line G/GEJC as well as preclinical data on the combination study of Osemitamab (TST001) with PD1 inhibitor (Press release, Transcenta, AUG 15, 2023, View Source [SID1234634433]).

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A brief summary of the presentations is as follows:

Title: First-line Osemitamab (TST001) plus Capecitabine and Oxaliplatin (CAPOX) for Advanced G/GE Cancer with CLDN18.2 Positive – Overall Survival data from Study TranStar102-Cohort C
Abstract#: 4038
Type: Abstract
Category: Oesophagogastric cancer
First Author: Prof. Lin Shen, Beijing Cancer Hospital

Title: Pharmacokinetics, Pharmacodynamics and Exposure Response Analyses of Osemitamab (TST001) in Patients with Locally Advanced or Metastatic Solid Tumors
Abstract#: 1556P
Type: Abstract
Category: Oesophagogastric cancer
First Author: Prof. Lin Shen, Beijing Cancer Hospital

Title: Osemitamab (TST001)，an ADCC Enhanced Humanized Anti-CLDN18.2 mAb, Demonstrated lmproved Efficacy in Combination with anti-PD-L1/PD-1mAb and Oxaliplatin/5-FU in Preclinical Tumor Models
Abstract#: 1570P
Type: Abstract
Category: Oesophagogastric cancer
First Author: Dr. Xueming Qian, Suzhou Transcenta Therapeutics Co., Ltd.

The ESMO (Free ESMO Whitepaper) Congress is the most influential oncology platform for clinicians, researchers, patient advocates, journalists and healthcare industry representatives from all over the world.

ESMO 2023 will disseminate the latest cutting-edge data, provide high quality education and unparalleled networking opportunities for oncologists and other stakeholders from all around the world. This year, the ESMO (Free ESMO Whitepaper) Congress will take place on October 20 to October 24, local time, in Madrid, Spain.

About Osemitamab (TST001)

Osemitamab (TST001) is a high affinity humanized anti- CLDN18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity ("ADCC"). It has shown potent anti-tumor activities in tumor xenograft models. Osemitamab (TST001) is the second most advanced CLDN18.2 targeting antibody being developed globally. Osemitamab (TST001) was generated using Transcenta’s Immune Tolerance Breaking Technology (IMTB) platform. Osemitamab (TST001) kills CLDN18.2 expressing tumor cells by mechanisms of ADCC. Leveraging advanced bioprocessing technology, the fucose content of Osemitamab (TST001) was significantly reduced during the production, which further enhanced NK cells mediated ADCC activity of Osemitamab (TST001). Clinical trials for Osemitamab (TST001) are ongoing in the U.S. and China (NCT05190575, NCT04396821, NCT04495296, NCT05608785 / CTR20201281). Osemitamab (TST001) was granted Orphan Drug Designation in the U.S. by FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) and pancreatic cancer.

On August 15, 2023 Gilead Sciences, Inc. (Nasdaq:GILD) and Tentarix Biotherapeutics reported that the companies established three multi-year collaborations leveraging Tentarix’s proprietary Tentacles platform to discover and develop multi-functional, conditional protein therapeutics for oncology and inflammatory diseases (Press release, Gilead Sciences, AUG 15, 2023, View Source [SID1234634432]). Designed to enhance both therapeutic benefit and safety, these molecules have the potential to conditionally target immune cells related to disease pathways without activating other immune cells that may create adverse events.

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"At Gilead, a key area of our research strategy is addressing immune dysregulation in oncology and inflammatory diseases," said Flavius Martin, M.D., Executive Vice President, Research, Gilead Sciences. "This early-stage collaboration with Tentarix will be highly synergistic to our ongoing efforts, building upon our growing strength in protein therapeutics, and may provide access to next-generation, multi-specific biologics."

"This collaboration is part of our strategy to join forces with innovators, like Gilead, who can help us rapidly advance new medicines to the clinic," said Paul Grayson, President and CEO of Tentarix Biotherapeutics. "Our technology has great promise and collaborating with Gilead to build out this pipeline helps broaden the development of multi-functional, antibody-based therapeutics, providing an excellent mechanism to validate our science with the ultimate goal of bringing these potential medicines to patients faster."

Across the three collaborations, Tentarix will receive upfront payments and an equity investment from Gilead totaling $66 million. In addition, Gilead has the option to acquire up to three select Tentarix subsidiaries containing the programs developed under the collaborations for $80 million per subsidiary.

Beginning in the first quarter of 2022, consistent with recent industry communications from the U.S. Securities and Exchange Commission (SEC), Gilead no longer excludes acquired IPR&D expenses from its non-GAAP financial measures. We expect the transaction with Tentarix to reduce Gilead’s GAAP and non-GAAP 2023 EPS by approximately $0.03 – $0.04.

On August 15, 2023 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of allogeneic cell therapies to treat a broad range of hematological and solid tumor malignancies, reported that it has initiated patient dosing in the first-in-human Phase 1 clinical trial of WU-NK-101 for patients with relapsed or refractory (r/r) acute myelogenous leukemia (AML) (Press release, Wugen, AUG 15, 2023, View Source [SID1234634431]). Additionally, Wugen announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to WU-NK-101 for the treatment of AML.

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WU-NK-101 is Wugen’s lead memory natural killer (NK) cell therapy product and is comprised of cells optimized for anti-cancer function. WU-NK-101 cells possess a unique cytokine-induced memory-like (CIML) phenotype that supports enhanced anti-tumor activity, robust trafficking, superior proliferation capacity, and metabolic flexibility, all of which contribute to treatment resilience in the adverse tumor microenvironment (TME). WU-NK-101 is produced with the company’s proprietary MonetaTM manufacturing platform, which enables robust generation of off-the-shelf memory NK cell-based therapies.

"The start of this clinical trial is a significant step forward in our memory NK cell program, which we believe offers significant advantages over other NK cell therapy approaches and has the potential to benefit patients with a number of tumor types," said Jan Davidson-Moncada, M.D., Ph.D., chief medical officer of Wugen. "Early clinical studies with memory NK cells demonstrated impressive response rates in patients with AML, even those with a high disease burden. We look forward to building on these data while advancing WU-NK-101 as a readily accessible allogeneic cell product. In tandem, we are proud to announce our Orphan Drug Designation for WU-NK-101, which will enhance our efforts to deliver this therapy to AML patients."

"Today’s news represents a significant milestone for Wugen, as WU-NK-101 is the first therapeutic candidate from our memory NK cell platform to enter the clinic," added Kumar Srinivasan, Ph.D., president and chief executive officer of Wugen. "Beginning in AML, where there remains a high unmet need for new therapeutic options, our goal is to deploy our memory NK cell platform to deliver next-generation, best-in-class allogeneic memory NK cell therapies to transform cancer care, including treatment of solid tumors."

The Phase 1 study is a global, open-label, dose-escalation, and cohort expansion study designed to characterize the safety and tolerability of WU-NK-101 in patients with r/r AML and determine the recommended Phase 2 dose. It will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-leukemic activity of WU-NK-101. WU-NK-101 will be administered as three weekly infusions in a 28-day cycle. Additional information is available on clinicaltrials.gov, identifier NCT05470140.

An abstract on the design of the Phase 1 trial was published in the November 2022 supplemental issue of Blood, the journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).

Memory NK cells have been clinically validated for safety and efficacy in AML. In addition, solid tumor preclinical studies of WU-NK-101 suggest efficacy in solid tumors alone or in combination with monoclonal antibodies.

The FDA Office of Orphan Products Development grants orphan designation for novel drugs or biologics being developed to treat a rare disease or condition affecting fewer than 200,000 patients in the United States. ODD qualifies the sponsor of the drug for various development incentives of the Orphan Drug Act, including potentially seven years of U.S. marketing exclusivity, tax credits for clinical research costs, clinical research trial design assistance, the ability to apply for annual grant funding and waiver of Prescription Drug User Fee Act filing fees.

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness, making it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML). Wugen is planning to initiate solid tumor studies of WU-NK-101 in combination with cetuximab. Studies of WU-NK-101 to date have shown promising robust in vivo activity in various tumor indications, retention of anti-cancer activity in TME, resistance to immune suppression, and enhanced activity with checkpoint inhibitors.

About the MonetaTM Platform

Wugen’s proprietary MonetaTM manufacturing platform is a robust, efficient, scalable process to generate off-the-shelf memory natural killer (NK) cell therapies with enhanced anti-tumor functionality. The MonetaTM platform uses cytokine fusion complexes for streamlined and consistent manufacturing, is free of feeder cells for enhanced safety, and integrates cryopreservation to allow convenient dosing options for cancer patients.