On December 18, 2024 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported that the Safety Review Committee (SRC) monitoring its Phase 1 clinical trial has unanimously approved opening of the third cohort of patients based on its favorable review of Cohort 2 safety data (Press release, TransCode Therapeutics, DEC 18, 2024, https://www.prnewswire.com/news-releases/transcode-therapeutics-announces-safety-review-committee-approval-of-opening-third-cohort-and-preliminary-results-from-first-cohort-in-phase-1-ttx-mc138-clinical-trial-302334447.html [SID1234649203]). The therapeutic candidate being evaluated, TTX-MC138, is TransCode’s lead candidate designed to inhibit microRNA-10b, or miR-10b, a microRNA critical to the emergence and progression of many metastatic cancers. The dose administered to the third cohort will be approximately double the dose administered to the second cohort.

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Several patients in the first and second cohort remain on study for continued treatment. No significant safety or dose limiting toxicities have been reported. Analysis of Cohort 1 data for pharmacokinetic (PK) and pharmacodynamic (PD) activity is ongoing and to date suggests that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical results and results from the previous Phase 0 clinical trial. Specifically, results from Cohort 1 confirmed the Phase 0 observation that TTX-MC138 shows evidence of pharmacodynamic activity in the presence of high baseline expression of miR-10b, reaching a 66% inhibition at 24 hours after infusion. Additionally, the concentration of TTX-MC138 in blood plasma as a function of dose in humans was found to be higher than achieved in nonclinical studies, suggesting a favorable pharmacokinetic profile.

"An SRC is a group of clinicians and experts that oversee patient safety during the conduct of a clinical trial. The SRC determines whether and how a study should proceed, including dose escalation and de-escalation decisions in accordance with the study design. The recommendations of the SRC are used to decide whether a clinical trial should be continued as designed, changed, or terminated," commented Sue Duggan, TransCode’s Senior Vice President of Operations. Duggan added, "Enrollment into the study continues based on the cumulative safety data review. Eligible patients may now be screened and scheduled in Cohort 3 for treatment with the next dose level of TTX-MC138 while preliminary data analysis continues."

About TTX-MC138

TTX-MC138 is a first-in-class therapeutic candidate that targets microRNA-10b, a microRNA widely believed to be a driver of metastatic disease. TransCode’s 2023 Phase 0 clinical trial produced evidence of delivery of a radiolabeled version of TTX-MC138 to metastatic lesions and pharmacodynamic activity, even at a microdose of the drug candidate, suggesting a broad therapeutic window for TTX-MC138.

About the Trial

TransCode’s Phase 1 clinical trial is a multicenter, open-label, dose-escalation and dose-expansion study designed to generate critical data to support evaluation of the safety and tolerability of TTX-MC138 in patients with a variety of metastatic solid cancers. While not an endpoint, the trial may provide early evidence of clinical activity of TTX-MC138. The trial comprises an initial dose-escalation phase followed by a dose-expansion phase. The primary objective of the dose-escalation phase is to evaluate the safety and tolerability of escalating dose levels of TTX-MC138. In the dose-expansion phase, the safety, tolerability and anti-tumor activity of TTX-MC138 will be further evaluated in certain tumor types selected based on preliminary results from the dose-escalation phase.

Further information is available at www.clinicaltrials.gov NCT Identifier: (NCT06260774).

On December 18, 2024 Inceptor Bio, a leading innovator in cell therapy, and GRIT Bio, a clinical-stage immunotherapy developer, reported a strategic partnership to advance IB-T101, a potentially best-in-class CAR-T therapy targeting solid tumors (Press release, Inceptor Bio, DEC 18, 2024, View Source [SID1234649204]).

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IB-T101, Inceptor Bio’s autologous CD70 CAR-T program, utilizes the proprietary OUTLAST platform to reprogram T cells for superior stemness, durability, and effector function in the hostile tumor microenvironment. The program targets clear cell Renal Cell Carcinoma (ccRCC), a cancer with significant unmet medical need and over 300,000 new cases annually worldwide.

"We are excited to partner with GRIT Bio to bring IB-T101 into the clinic and address the urgent need for effective solid tumor therapies," said Dr. Matthias Schroff, CEO of Inceptor Bio. "This collaboration highlights the potential of our proprietary OUTLAST platform, and the data generated will play a critical role in advancing the program as we strive to deliver best-in-class therapies for patients."

Dr. Mengyang Chong, Chief Business Officer of GRIT Bio, shared, "Partnering with Inceptor Bio allows us to bring a highly differentiated CAR-T program to patients. IB-T101 has the potential to transform the treatment landscape for solid tumors, and we are eager to contribute our expertise in clinical development and manufacturing to accelerate its progress."

Under the terms of the agreement, Inceptor Bio will grant GRIT Bio an exclusive license for IB-T101 in China. GRIT Bio will oversee development, manufacturing, and commercialization. Inceptor Bio is eligible to receive milestone payments and royalties upon IB-T101 achieving certain response criteria and plans to leverage clinical data from this collaboration to support regulatory submissions and development in other regions.

This partnership represents a critical step in Inceptor Bio’s mission to validate the OUTLAST platform as a best-in-class approach for engineered T cell therapies and bring transformative treatments to patients worldwide.

On December 18, 2024 Xcovery Holdings, Inc., an oncology focused pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has approved ensartinib (Ensacove, Xcovery Holdings, Inc.) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Xcovery, DEC 18, 2024, View Source [SID1234649205]). This approval marks an important advancement in providing a new first line option for patients with ALK-positive NSCLC.

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Ensartinib is an ALK tyrosine kinase inhibitor (TKI) designed to improve outcomes for patients with ALK-positive NSCLC. The FDA approval is based on data from the pivotal global Phase III eXalt3 clinical trial, in which ensartinib demonstrated statistically significant improvements in progression-free survival (PFS) over crizotinib.

"The approval of Ensartinib by FDA brings another new medicine to patients battling ALK-positive NSCLC, expanding the options to optimize treatment in the first-line setting. This result could not have been achieved without the dedication of our team members and the support of patients, physicians, and all stakeholders involved in the clinical development of Ensartinib," said Giovanni Selvaggi, Chief Medical Officer of Xcovery.

"FDA approval of Ensartinib represents a significant milestone in Xcovery’s mission to advance precision medicine for patients with cancer," said Kevin Sang, CEO of Xcovery. "In addition to Ensartinib, we are continuing our efforts in developing more pipeline targeted drugs for patients worldwide."

About Ensartinib

Ensartinib is a next generation ALK inhibitor jointly developed by Xcovery and Betta Pharmaceuticals. It is indicated for the treatment of adult patients with ALK-positive locally advanced or metastatic NSCLC.

On December 18, 2024 Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, reported that Tom Miller, Ph.D., Iambic’s Chief Executive Officer and Co-Founder, will present at the 43rd Annual JP Morgan Healthcare Conference (Press release, Iambic Therapeutics, DEC 18, 2024, View Source [SID1234649206]). The presentation will take place on Tuesday, January 14th, at 5 p.m. PT at the Westin St. Francis Hotel in San Francisco.

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Dr. Miller will detail progress and anticipated milestones for Iambic’s emerging pipeline of development candidates, as well as advances to its AI drug discovery platform. The Company’s pipeline currently includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs.

On December 18, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported the expansion of its pipeline with a novel FAP-targeted radiopharmaceutical for the diagnosis and treatment of cancer (Press release, Clarity Pharmaceuticals, DEC 18, 2024, View Source [SID1234649191]).

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FAP is expressed on cancer associated fibroblasts (CAFs), a particular cell type found in the tumour microenvironment (cancer ‘infrastructure’ called the tumour stroma). CAFs are found in a broad range of cancers (e.g. breast, colorectal, pancreatic, lung, brain and ovarian cancers), but only minimally in normal tissue, making FAP a promising pan-cancer target for both imaging and treatment of cancers1. CAFs form part of the environment surrounding the cancer cells, and they can promote cancer growth and the spread of the tumour throughout the body2. Targeting the tumour stroma is an alternative way to treat cancer whereby the architecture of the tumour mass is targeted rather than the tumour cells directly.

Clarity’s Targeted Copper Theranostic (TCT) targeting FAP was developed at the benchtop of Australian science, with a clear understanding of other FAP-targeted radiopharmaceuticals in development and the intent of overcoming the low uptake and retention of these agents in tumours. This was achieved by utilising some novel chemistry, and by combining an industry leading FAP inhibitor with the proprietary SAR chelator technology. The SAR Technology enables the use of copper-64 (64Cu) for imaging and copper-67 (67Cu) for the targeted treatment of various cancers.

Similar to how Clarity developed its PSMA-targeted prostate cancer agent as a dimer, SAR-bisPSMA, which was designed to improve tumour uptake and retention, the Company created a novel dimer for its FAP-targeted radiopharmaceutical, SAR-bisFAP. With the benefit of comparing this novel molecule to other FAP radiopharmaceuticals in development as well as to a monomer equivalent (SAR-monoFAP), the dimer SAR-bisFAP has shown increased tumour uptake and retention over 24 hours in pre-clinical models.In addition to comparing the mono and dimer versions of the product, Clarity compared the dimer, 64Cu-SAR-bisFAP, to an industry standard FAP-targeted monomer called 68Ga-FAPI-46. Using a FAP-expressing melanoma cell line (SK-MEL187) in this experiment, at 1-hour post-injection 64Cu-SAR-bisFAP had approximately 4 times the uptake in the cancer compared to 68Ga-FAPI-46. The improvements in uptake and retention of 64/67Cu-SAR-bisFAP compared to first-generation FAP compounds, such as FAPI-46, are key attributes for the development of next-generation radiopharmaceuticals.

Clarity is currently conducting additional investigations to enable a Phase I clinical trial, which could commence in late 2025. Research into the potential clinical use of Clarity’s FAP agent has begun with several pre-clinical studies in diagnostics (utilising 64Cu-SAR-bisFAP), which will be followed by exploring treatment opportunities of cancers based on their unmet medical needs (using 67Cu-SAR-bisFAP).

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "Our commitment to always putting science first at Clarity has placed us in an enviable position in radiopharmaceuticals globally. This has allowed us, yet again, to create a novel product at the benchtop to overcome the shortcomings of competing radiopharmaceuticals by increasing the uptake and retention of the molecule over time. Coupled with the use of the perfect pairing of copper isotopes, this facilitates the use of same-day and next-day imaging, addressing the issue of low sensitivity of short half-life products using gallium-68 and fluorine-18, as well as potentially enhancing the therapeutic benefit through increasing the amount and retention of the product at the site of tumours. This is especially the case for FAP-targeted radiopharmaceuticals that offer so much hope as a pan-cancer but suffer the issue of low uptake and retention at the tumour site.

"We are excited to continue growing our pipeline of TCTs through our Discovery Program, utilising the unique advantages of copper isotopes, enabled by our proprietary SAR Technology. Unlike other chelator technologies that leak copper in vivo, the SAR Technology securely holds copper over time, unlocking a myriad of advantages of the "perfect pairing" of copper-64 for imaging and copper-67 for therapy, such as next-day imaging, supply, logistical and environmental advantages. Having strong intellectual property around the SAR Technology, as well as our novel products, with over 28 patent families now within the Company, we continue expanding our pipeline of next-generation radiopharmaceuticals. The development of these new products is only possible due to the utilisation of great chemistry combined with new promising targets and our proprietary chelator, thereby enabling a multitude of new products for indications with high unmet needs. By going back to the drawing board and conducting comprehensive research and testing, we were able to create a unique product that achieves the outcomes we were looking for of improving uptake and retention in tumours. The tumour targeting, retention and pharmacokinetic data we have seen to date with SAR-bisFAP is impressive, and we look forward to progressing this product in clinical trials and are excited to explore the pan-cancer targeting potential in a range of indications with high unmet needs."

About 64/67Cu-SAR-monoFAP and 64/67Cu-SAR-bisFAP
64/67Cu-SAR-monoFAP and 64/67Cu-SAR-bisFAP are unregistered products. Their safety and efficacy have not been assessed by health authorities such as the US Food and Drug Administration (FDA) or the Therapeutic Goods Administration (TGA). Outcomes from human clinical trials may differ from pre-clinical findings. There is no guarantee that these products will become commercially available.