On May 24, 2024 Shanghai Juncell Therapeutics Co., Ltd. (Juncell Therapeutics), a clinical-stage biotech developing innovative Tumor-Infiltrating Lymphocyte (TIL) therapies for cancers, reported latest clinical research results on GC203 (a novel non-viral vector gene-modified TIL therapy engineered with membrane-bound IL-7) (Press release, Juncell Therapeutics, MAY 24, 2024, View Source [SID1234643696]). These data will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place on May 31 – June 4, 2024.

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Researchers tested GC203 on patients diagnosed with recurrent ovarian cancer, without the combination of IL-2 administration or aggressive lymphodepletion. The objective of the study was to determine the safety and efficacy of this treatment. A total of 20 patients were enrolled between 09/2021 and 01/2024 in the open-label single-center trial, in which 18 patients were evaluable. The evaluable patients were with an ECOG PS of 1 (55.6%) or 2 (44.4%) and received a median of 5 previous systemic therapies (range: 2-11). 9 (50%) patients had 3 or more tumor lesions. The median target lesion size was 57 (range: 13-146) mm.

GC203 showed promising results in patients with recurrent or metastatic ovarian cancer. The safety profile was improved significantly compared with conventional TIL therapies, thanks to a low-intensity pretreatment and the elimination of IL-2 combination. Most of the Adverse Events (AEs) were grade 1 or grade 2 and could be alleviated or cured by symptomatic treatment. No grade 5 event occurred. By the cutoff date of 01/2024, the investigator-assessed Objective Response Rate (ORR) was 33.3% (95% CI: 16.3 – 56.3), including 11.1% Complete Response (CR). The Disease Control Rate (DCR) was 83.3% (95% CI, 60.8 – 94.2). And the 12-month Overall Survival (OS) rate was 68.8% (95% CI: 49.3 – 95.9). The median OS was not mature as data cut-off.

Presentation Details

Abstract Number: 5552

Abstract Title: A phase I single-arm, open-label trial of engineering tumor-infiltrating lymphocytes with membrane-bound lL-7 for recurrent ovarian cancer.

Session Type and Title: Poster Session – Gynecologic Oncology

Poster Presentation Time: 9:00 AM – 12:00 PM CDT, June 3, 2024

Presenter: Dr. Jing Guo, Shanghai Tenth People’s Hospital

The abstract is available on the ASCO (Free ASCO Whitepaper) website.

About Ovarian Cancer

Ovarian cancer has the highest mortality rate among gynecologic cancers. 70% of patients are diagnosed at an advanced stage. 70% of patients with advanced ovarian cancer have a survival time of less than five years. More than 200,000 people worldwide die from ovarian cancer each year, indicating a significant unmet clinical need. The primary treatment for advanced ovarian cancer is platinum-based chemotherapy. Ovarian cancer is insensitive to immunotherapy, with an ORR of less than 10%. Effective treatment options are limited.

About GC203

GC203 is a novel non-viral vector gene-modified TIL therapy developed leveraging Juncell Therapeutics’ proprietary DeepTIL cell expansion platform and NovaGMP gene modification platform. DeepTIL enables TILs to be potent enough that no IL-2 combination will be required after infusion, and the intensity of pretreatment could be lower. NovaGMP modifies T cells with a high efficiency comparable with the Lentiviral vector in an economic way. GC203 is engineered with self-associating membrane-bound interleukin-7, which can maintain the stemness of memory T cells, activate internal immune cells and avoid systemic toxicities.

On May 24, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that senior leadership plans to present at the following conferences and events (Press release, Iovance Biotherapeutics, MAY 24, 2024, View Source [SID1234643678]):

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TD Cowen 5th Annual Oncology Innovation Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper)
Fireside Chat: May 28, 2024 at 3:00 p.m. ET
Virtual
Iovance ASCO (Free ASCO Whitepaper) Investor/Analyst Event
Presentation and Key Opinion Leader Panel Discussion: May 31, 2024 at 7:15 p.m. ET
Chicago, IL and Virtual
Jefferies Global Healthcare Conference
Fireside Chat: June 6, 2024 at 9:30 a.m. ET
New York, NY
Goldman Sachs Global Healthcare Conference
Fireside Chat: June 10, 2024 at 2:40 p.m. ET
Miami, FL
Iovance 2024 Annual Meeting
June 11, 2024 at 11:00 a.m. ET
Virtual
The live and archived webcasts will be available at View Source

On May 24, 2024 STORM Therapeutics Ltd. (STORM), the clinical stage company pioneering cellular reprogramming through RNA modifications to treat disease, reported that it will be presenting interim clinical data on its first-in-class lead product, STC-15 at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago, US from May 31 to June 4, 2024 (Press release, STORM Therapeutics, MAY 24, 2024, View Source [SID1234643697]).

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The poster presentation, entitled ‘Phase 1 Dose Escalation and Cohort Expansion Study Evaluating Safety, PK, PD and Clinical Activity of STC-15, a METTL3 Inhibitor, in Patients with Advanced Malignancies’, describes findings from STORM’s ongoing dose escalation and expansion Phase 1 clinical study to evaluate STC-15, an oral and highly selective small molecule inhibitor of METTL3, in advanced cancer patients. These interim results will focus on safety, pharmacokinetics, target modulation and tumor assessments to support future clinical studies. STC-15 is the first molecule specifically targeting an RNA methyltransferase enzyme to enter clinical development.

Preclinical data has demonstrated that METTL3 inhibition stimulates immune cells and activates interferon pathways, leading to the destruction of tumor cells. The poster presentation will detail the study design, patient demographics, safety data, pharmacokinetics, METTL3 target engagement, mechanistic biomarker data, and assessments of clinical activity.

Details of the poster presentation are as follow:

Poster Title: Phase 1 dose escalation and cohort expansion study evaluating safety, PK, PD and clinical activity of STC-15, a METTL3 inhibitor, in patients with advanced malignancies
Presenter: Justin Moser at HonorHealth Research Institute
Authors: Justin Moser[1], Kyriakos Papadopoulos[2], Jordi Rodon Ahnert[3], Yaara Ofir-Rosenfeld[4], Josefin-Beate Holz[4]
Organizations: [1]HonorHealth Research Institute, [2]START San Antonio, [3]The University of Texas MD Anderson Cancer Center, [4]Storm Therapeutics Ltd
Poster Session: Developmental Therapeutics—Immunotherapy
Session Date and Time: Saturday June 1, 2024, 9:00 AM – 12:00 PM CDT
Poster Board Number: 65
Abstract Presentation Number: 2586

The Abstract is available on the ASCO (Free ASCO Whitepaper) online itinerary planner here, and on the STORM website here.

On May 24, 2024 Allogene Therapeutics, Inc. (the "Company"), Overland Pharmaceuticals (CY) Inc. ("Overland") and Allogene Overland Biopharm (CY) Limited (the "JV Company") reported to have entered into a Share Exchange Agreement pursuant to which Overland’s cell therapy business merged into the JV Company (the "Organizational Restructuring").

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As background, the JV Company was originally formed on December 14, 2020 by Overland and the Company. Upon formation of the JV Company, the Company contributed an exclusive license to develop, manufacture and commercialize specific Company product candidates targeting BCMA, CD70, FLT3 and DLL3 (the "Licensed Products") in China, Taiwan, South Korea and Singapore (the "Territory"), with the Company retaining exclusive rights to the Licensed Products outside the Territory (the "Exclusive License Agreement"), and Overland contributed $117 million in upfront and certain quarterly cash payments. In return, the Company received a $40 million upfront payment and Seed Preferred Shares representing 49% of the JV Company’s outstanding stock and Overland received Seed Preferred Shares representing 51% of the JV Company’s outstanding stock.

Under the Share Exchange Agreement, the JV Company acquired from Overland a 100% equity interest in Overland Pharmaceuticals (US) Inc. ("Overland US"). Overland US includes certain research and development, clinical, and general and administrative staff, as well as select cell therapy assets, including its lead program, OL-101, an autologous GPRC5D-BCMA bispecific dual targeting CAR-T for refractory multiple myeloma. Upon completion of the closing of the share exchange, Overland US became a wholly owned subsidiary of the JV Company, Overland’s ownership increased to 81.54%, the Company’s ownership decreased to 18%, and the Ordinary Shares issuable under the share incentive plan of the JV Company equaled 0.46% of the capitalization of the JV Company on an as-converted and fully-diluted basis. In addition, the JV Company increased the total number of Ordinary Shares issuable under its share incentive plan, which resulted in diluting Overland’s and the Company’s ownership to 69.63% and 15.37%, respectively, and the Ordinary Shares issuable under the share incentive plan of the JV Company were increased to 15% of the capitalization of the JV Company on an as-converted and fully-diluted basis.

Under a separate agreement between Overland and HH BioPharma Holdings Ltd. ("HBP") executed on May 24, 2024, Overland distributed all Series Seed Preferred Shares of the JV Company held by Overland to HBP and HBP has assumed all rights and obligations attached to such Shares and all rights and obligations of Overland under the Share Exchange Agreement.

In connection with the Organizational Restructuring, on May 24, 2024, the Company and Allogene Overland BioPharm (PRC) Co., Limited (the "Licensee"), an indirect wholly owned subsidiary of the JV Company, entered into a First Amendment to Exclusive License Agreement (the "Amendment") to amend and supplement certain provisions of the Exclusive License Agreement dated December 14, 2020 between the Company and the JV Company which has since assigned all of its rights and obligations under the Exclusive License Agreement to the Licensee. Under the Amendment, the Company continues to grant the JV Company an exclusive license to develop, manufacture, and commercialize the Licensed Products in the Territory, with the Company retaining exclusive rights to the Licensed Products outside the Territory, and the royalty obligations to the Company were amended to a flat mid single-digit royalty on net sales in the Territory that are no longer subject to reductions as previously provided. The Amendment also provides the Company with additional rights to terminate the Exclusive License Agreement in its entirety or with respect to the relevant Licensed Product(s) if the Licensee fails to initiate manufacturing technology transfer with respect to a Licensed Product as agreed in the Amendment, or if HBP commits a funding default or a material breach of its representations, warranties, or covenants under the Share Exchange Agreement. The Amendment also provides that the Exclusive License Agreement will terminate automatically if the Company’s ownership in the JV Company falls below 7.5% (other than due to the Company’s sale of the Shares of the JV Company), unless at that time the JV Company and the Company have mutually agreed on the manufacturing technology transfer plan for the Licensed Product(s) and the JV Company elects to continue the license for such Licensed Product(s) with increased milestones and royalties. Under the Amendment terms such increased milestones and royalties consist of up to $115 million in milestone payments for each Licensed Product and tiered mid single-digit to low double-digit royalties on net sales in the Territory.

In connection with the Organizational Restructuring, on May 24, 2024, the Company, HBP, and the JV Company also entered into an Amended and Restated Shareholders’ Agreement which amends and restates the prior Shareholders’ Agreement dated December 14, 2020 among the Company, Overland, and the JV Company in its entirety. Pursuant to the Amended and Restated Shareholders’ Agreement, the board of directors of the JV Company will be comprised of five directors, with three directors designated by HBP, one director designated by the Company, and one director serving as the chief executive officer of the JV Company. The Amended and Restated Shareholders’ Agreement provides each of the Company and HBP certain shareholder-level consent rights, certain director-level consent rights, registration rights, information rights, and pre-emptive rights for future equity issuances. The Amended and Restated Shareholders’ Agreement shall terminate upon the consent of the parties, provided that its provisions with respect to director designation rights, shareholder-level consent rights, director-level consent rights, information rights, and pre-emptive rights shall terminate upon a qualified IPO or sale of the JV Company or its assets.

The foregoing description of the material terms of the Share Exchange Agreement, the Amended and Restated Shareholders’ Agreement and the Amendment is qualified in its entirety by reference to the complete text of such agreements, which the Company intends to file with the Securities and Exchange Commission as exhibits to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024.

On May 24, 2024 Tyligand Bioscience, a clinical-stage biotechnology company focused on the discovery and development of innovative cancer therapies, reported that the first patient had been dosed in the Phase 1/2 trial of TSN1611 for the treatment of KRAS G12D mutant solid tumors in the United States (Press release, Tyligand Bioscience, MAY 24, 2024, View Source [SID1234643698]). The program has been cleared for IND by U.S. FDA and China NMPA in Feb and April 2024, respectively.

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TSN1611 is a highly selective and orally bioavailable small molecule targeting the G12D mutant of KRAS oncogene, with excellent enzymatic and cellular activities. It effectively engages both the ON-state (GTP-bound) and OFF-state (GDP-bound) of KRAS G12D. TSN1611 has demonstrated superior in vivo anti-tumor activity with a durable response across multiple animal models. TSN1611 features favorable physicochemical properties, oral pharmacokinetic profiles, and notable brain penetration potential to address a large unmet medical need.

The ongoing first-in-human, multi-center clinical trial (NCT06385925) is designed to assess the safety, tolerability, pharmacokinetic profile, and preliminary anti-tumor activity in patients with advanced solid tumors harboring the KRAS G12D mutation. Patient recruitment is currently underway in the United States, with plans to initiate in China in the coming months.

"Preclinical profile indicated the potential of TSN1611 as a best-in-class molecule for treating cancers driven by KRAS G12D," said Dr. Tony Zhang, PhD., CEO of Tyligand Bioscience, "We are proud of our teams for the creativity, quality and speed in the discovery and early development efforts, and grateful for the support from our partners and investors in advancing TSN1611 one step closer toward the patients in need."