On July 6, 2023 TAE Life Sciences, a pioneering company in the field of cancer treatment, reported the results from early testing of its TC440 boron-containing dipeptide compound for Boron Neutron Capture Therapy (BNCT). The findings suggest that TC440, along with its counterpart TC442, holds promise in revolutionizing cancer treatment strategies (Press release, TAE Life Sciences, JUL 7, 2023, View Source [SID1234633115]).

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"Finding safe and effective ways to treat a variety of cancers is of utmost importance in our mission to improve and transform cancer care. The work we are doing at TAE Life Sciences to create new drugs like TC440 for BNCT is critical in this endeavor," said Kendall Morrison, Chief Science Officer, TAE Life Sciences. "The promising preliminary results from our early testing indicate that these exciting new peptides hold significant potential in revolutionizing cancer treatment strategies. These findings highlight the immense potential of TC440 in enhancing the therapeutic efficacy of BNCT, bringing us closer to a future where safer and more effective treatments are available for cancer patients."

TC440 and TC442 belong to a family of dipeptides that were synthesized at TAE Life Sciences using cuttingedge BPA Structural Analysis Relationship (SAR) chemistry. These compounds have demonstrated superior solubility compared to the widely used Boronophenylalanine (BPA), enabling the formulation of highly concentrated solutions. Formulations of TC440 and TC442 in fructose at 150 mg/ml have been achieved, providing a remarkable advancement in delivering boron to tumors. By leveraging the dipeptides’ improved solubility, higher tumor boron delivery was achieved in multiple xenograft models, showcasing the superior uptake of TC440 and TC442. In addition to enhanced solubility, TC440 and TC442 possess the ability to be internalized via LAT1 transporters and PEPT1, even in LAT1 negative cell lines.

One of the most exciting discoveries is that these compounds deliver two to three times more boron than BPA in multiple human xenograft models and have a longer half-life compared to BPA. This increased boron delivery capability and longer half-life hold immense potential in enhancing the therapeutic efficacy of BNCT as a treatment modality.

To further investigate the therapeutic applications of TC440 and TC442, TAE Life Sciences is collaborating on BNCT experiments with the Department of Radiobiology at the National Atomic Energy Commission (CNEA) with Dr. Andrea Monti Hughes and Team, from Argentina. Initial studies conducted in the hamster cheek pouch oral cancer model have yielded encouraging preliminary results and were presented at 61st Annual PTCOG Conferences held in Spain, this year.

The ongoing study conducted in the hamster cheek pouch oral cancer model, which closely mimics the development of precancer and malignant human oral tumors, is a critical milestone in the research journey. The model provides a unique tumor environment surrounded by precancerous tissue, allowing researchers to investigate BNCT’s dose-limiting effects, as observed in field-cancerized oral mucosa in head and neck cancer patients.

In this preliminary study, an 800 mg TC440/kg dose has demonstrated an increase in boron uptake compared to the 300 mg BPA/kg dose typically administered during testing, while maintaining higher tumor/blood and tumor/normal tissue ratios. However, similar boron concentrations and ratios were achieved compared to 800 mg BPA/kg. Unlike the BPA solution, the TC440 formulation exhibited no precipitation issues, providing a practical advantage.

When evaluating the therapeutic effect of BPA/BNCT versus TC440/BNCT, the preliminary study unveiled promising results. TC440 demonstrated a doubling of complete responses compared to BPA/BNCT protocols, particularly in medium and large hamster tumors treated with TAE/BNCT. Additionally, partially responded tumors treated with TC440 that exhibited a 50% in volume reduction were higher than in the BPA/BNCT group.

Ongoing studies to confirm these early findings are underway. Ongoing studies will further explore the potential of new dipeptides from TAE Life Sciences and expand upon these exciting preliminary findings. "The study of new boron compounds that could increase significantly BNCT therapeutic effect while preserving dose-limiting tissues is of utmost importance in BNCT. Huge efforts have been done for many years around the World, and radiobiological studies in in vivo models are a critical step to decide if a boron compound could be consider potentially useful in a clinical setting" said Andrea Monti Hughes (CNEA/CONICET, Argentina).

The groundbreaking discovery of TC440 and its therapeutic potential for cancer treatment using BNCT marks a significant milestone in the field of oncology. The company will continue to investigate the therapeutic potential of its TC440 and TC442 boron-containing drugs and will have the results published in a peer-reviewed scientific journal.

TAE Life Sciences is committed to advancing innovative solutions to address the challenges of cancer treatment, with the goal of improving patient outcomes and transforming the future of cancer care. Morrison will be presenting the results of this collaborative study with CNEA at the 19th Annual Japanese Neutron Capture Therapy Congress in Kyoto, Japan.

About BNCT

BNCT is a combination treatment based on the reaction that occurs when a non-toxic compound containing boron-10 is irradiated with a low-energy neutron beam. BNCT differs radically from other radiation therapies and shows promise in becoming the next-generation cancer treatment. Research has shown that BNCT has the capability of killing cancer cells that are resistant to traditional radiation therapy with limited harm to healthy tissue. Current advances in both neutron radiation technology and medicinal boron drug targeting are enabling BNCT’s potential to improve patient care while also improving treatment economics. To date, approximately 2,000 patients have been treated with BNCT at research sites worldwide.

On July 7, 2023 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that it will present new data on its gene expression profile (GEP) risk-stratification test for patients with cutaneous squamous cell carcinoma (SCC), DecisionDx-SCC, and its GEP risk-stratification test for patients with cutaneous melanoma (CM), DecisionDx-Melanoma, at the American Head & Neck Society’s (AHNS) 11th International Conference on Head and Neck Cancer, being held July 8-12 in Montréal, QC, Canada (Press release, Castle Biosciences, JUL 7, 2023, View Source [SID1234633114]).

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Castle’s podium presentation on DecisionDx-SCC will share data demonstrating significantly improved metastatic risk prediction in patients with SCC of the head and neck (SCC-HN) when the test’s results are used both independently and in conjunction with American Joint Committee on Cancer 8th edition (AJCC8) and Brigham and Women’s Hospital (BWH) staging systems. Details are as follows:

Abstract ID: 128656 | Podium presentation: Improved metastatic risk prediction with the 40-gene expression profile (40-GEP) test supports its use for risk-aligned decision making for patients with high-risk cutaneous squamous cell carcinoma of the head and neck
Presenter and Study Author: Jason G. Newman, M.D., F.A.C.S., Department of Otolaryngology Head and Neck Surgery at Medical University of South Carolina
Session Date/Time: Sunday, July 9, 1:45-3:15 p.m. Eastern time
Session Name: Proffered Papers 9 – Skin 1 and Hot Topic Session

"Traditional staging methods rely on a limited set of clinicopathologic risk factors to categorize cancer patients into different stages," said Newman. "While these factors provide important information, they may not fully capture the underlying biological heterogeneity and variability in tumor behavior. The study data demonstrated that using DecisionDx-SCC test results in combination with these traditional staging approaches can improve prognostic accuracy to help optimize and personalize treatment choices based on a patient’s unique, biological risk profile."

This multi-center study expands on a previously published study1 and analyzed data from 622 patients with high-risk SCC-HN. In the study, DecisionDx-SCC significantly stratified patients according to their biologic risk of metastasis, independent of the clinicopathologic risk factors used in AJCC8 and BWH staging systems (p<0.0001). Additionally, the metastatic risk predictions provided by AJCC8 and BWH staging were significantly improved when DecisionDx-SCC test results were included. The data show that DecisionDx-SCC contributes independent prognostic value to the prediction of metastatic risk in SCC-HN patients, relative to staging alone, which can help clinicians make informed decisions regarding treatment and follow-up care. These may include closer monitoring, more frequent imaging scans and the timely initiation of adjuvant treatments to mitigate metastatic risk and improve patient outcomes.

Castle will also present a poster highlighting data from a large study of real-world, unselected patients with head and neck CM (n=985) showing that combining DecisionDx-Melanoma test results with AJCC8 staging significantly improved risk prediction over either alone.

Abstract ID: 128718 | Poster presentation: The 31-gene expression profile test stratifies melanoma-specific survival among patients with head and neck cutaneous melanoma tumors: A Surveillance, Epidemiology, and End Results (SEER) Program Collaboration
Presenter and Study Author: Matthew Goldberg, M.D., Senior Vice President, Medical, Castle Biosciences
Poster Viewing Dates and Times:

Sunday, July 9, 5:15-6:45 p.m. (Welcome Reception)
Monday, July 10, 10 a.m. – 4 p.m. and 5:30-7 p.m. (Wine and Cheese Poster Walk)
Tuesday, July 11, 10 a.m. – 4 p.m.
In the study, DecisionDx-Melanoma testing and AJCC8 staging were independent predictors of mortality. The DecisionDx-Melanoma test classified 40% of the patients as having an increased risk of dying from their disease (Class 1B-2B test result) compared to 15% who were classified as having an increased risk by AJCC8 staging (IIB-III). Overall, the data demonstrated that combining the test’s results with AJCC8 staging significantly improved risk prediction over use of either alone, providing actionable information that can enable risk-aligned patient care.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), Class 2A (moderate) or Class 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management. Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile risk stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient’s individual risk of sentinel lymph node (SLN) positivity and a patient’s personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma’s clinical value is supported by more than 40 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through March 31, 2023, DecisionDx-Melanoma has been ordered more than 128,000 times for patients diagnosed with cutaneous melanoma.

More information about the Castle’s tests can be found at www.CastleTestInfo.com.

On July 7, 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 has received approvals from China CDE (Center for Drug Evaluation) and South Korea MFDS (Ministry of Food and Drug Safety) to initiate TranStar 301 global Phase III pivotal trial of Osemitamab (TST001) in combination with Nivolumab and chemotherapy for the first-line treatment of patients with HER2 negative, CLDN18.2 expressing locally advanced or metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma (Press release, Transcenta, JUL 7, 2023, View Source [SID1234633113]). In addition, we are in the process of EU and FDA regulatory interaction.

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Gastric cancer (GC) is the 4th leading cause of cancer death worldwide, accounting for about 7.7% of all cancer related mortality. The five year survival rate for gastric cancer is still around 30%. Nivolumab, an anti-PD-1 antibody, has been approved globally for the first line treatment of patients with advanced or metastatic HER2-negative G/GEJ cancer.

Osemitamab (TST001) is a second generation humanized CLDN18.2 targeting antibody with enhanced ADCC. It has shown anti-tumor activities in preclinical models with a broad range of CLDN18.2 expression. Recently, the Company presented efficacy data of Osemitamab (TST001) in combination with CAPOX as the first-line treatment of G/GEJ cancer at 2023 ASCO (Free ASCO Whitepaper) annual meeting and 2023 ESMO (Free ESMO Whitepaper) GI. Among 64 patients with CLDN18.2 positive (defined as: IHC membrane staining ≥10% tumor cells with ≥1+ intensity per LDT assay, selecting approximately 55% of the screened patients) were treated, 49 at the dose of 6mg/kg. The data showed that the estimated median progression-free survival was 9.5 months from all dose groups, consistent across all CLDN18.2 expression levels, with a median duration of response of 9.9 months.

Preclinical studies have demonstrated synergistic anti-tumor activities between Osemitamab (TST001) and anti-PD-1 antibodies in CLDN18.2 expressing tumor models. Recently Transcenta has reported that 82 patients had been enrolled in TranStar 102 to assess the safety and efficacy of Osemitamab (TST001) in combination with Nivolumab and CAPOX. So far, the combination is well tolerated.

TranStar 301 is a global randomized, double-blind, placebo-controlled Phase III trial designed to evaluate Osemitamab (TST001) in combination with Nivolumab plus chemotherapy as the first-line treatment for patients with locally advanced or metastatic HER2 negative, CLDN18.2 expressing G/GEJ adenocarcinoma.

"We are actively progressing our plans to develop Osemitamab (TST001) in combination with Nivolumab and chemotherapy as first-line treatment for CLDN18.2 expressing G/GEJ adenocarcinomas in a large multinational Phase III clinical trial. CDE and MFDS approvals are exciting milestones, with several others coming soon. We are looking forward to sharing more information as it becomes available." said Dr. Caroline Germa, Transcenta’s Executive Vice President, Global Medicine Development and Chief Medical Officer.

References:
[1] 2023 ESMO (Free ESMO Whitepaper) Poster: View Source
[2] 2023 ASCO (Free ASCO Whitepaper) Poster: View Source

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 July 7, 2023 280Bio, Inc. a clinical stage biotechnology company focused on the development of precision oncology medicines, reported that the U.S. Food and Drug Administration (FDA) has granted the company’s Investigational New Drug (IND) application for the investigational drug YL-17231, a small molecule inhibitor of RAS signaling (Press release, 280Bio, JUL 7, 2023, View Source [SID1234633112]). The approval enables the initiation of the Phase 1 clinical study for YL-17231 in the US. KRAS, NRAS and HRAS genes are frequently mutated in many tumor indications with the oncogenic mutations leading to tumor cell growth. YL-17231 demonstrated in pre-clinical research to potently inhibit tumor cell proliferation in vitro and in vivo, exhibiting activity with a variety of RAS mutations, including tumors that have become resistant to KRAS G12C inhibitors. 280Bio will initiate a Phase 1 study for the treatment of advanced cancer patients with RAS mutations in their tumors.

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"The IND approval by the FDA enables 280Bio to initiate the Phase 1 clinical trial of our novel KRAS inhibitor marking a major milestone for the company’s clinical development program." said Michael Hui, Chief Executive Officer of 280Bio Inc., "We are excited to explore the therapeutic potential of YL-17231 targeting a broad patient population with RAS mutations to potentially create a transformative therapy option."

280Bio will advance YL-17231 into a U.S.-based Phase 1 clinical study at multiple clinical cancer research centers in the U.S including the MD Anderson Cancer Center, Houston, Texas. The Company plans to start enrollment of patients in the dose escalation part of Phase1 in the fourth quarter of 2023.

Reflecting on the high unmet need for newly developed cancer agents, Dr. Zusheng Xu, General Manager and Head of Research and Development of Yingli Pharma, said "We are excited that YL-17231 has emerged from the company’s discovery platform, exemplifying the utility of our strong medicinal chemistry capabilities. YL-17231 has a broader activity than many current KRAS inhibitors and demonstrated strong inhibition of in vivo KRAS mutant xenograft tumor growth in our preclinical investigations. With its excellent pharmacologic properties, we are hopeful that YL-17231 will demonstrate to be safe and efficacious during continuous oral dosing in patients."

YL-17231 has been co-developed by 280Bio and Yingli Pharma and emerges from the strategic collaboration of 280Bio with The University of Texas MD Anderson Cancer Center, where further preclinical research of the investigational drug is continuing.

On July 7, 2023 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncology, inflammatory, and liver diseases, reported it has been invited to present at the Emerging Growth Conference on Thursday, July 13, 2023 at 11:25 AM ET (Press release, Can-Fite BioPharma, JUL 7, 2023, View Source [SID1234633111]).

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This live, interactive online event will give existing shareholders and the investment community the opportunity to interact with Can-Fite’s CEO, Motti Farbstein, in real time.

Mr. Farbstein will present and subsequently open the floor for questions. Please submit your questions in advance to [email protected] or ask your questions during the event and Mr. Farbstein will do his best to get through as many of them as possible.

Please register here LINK to ensure you are able to attend the conference and receive any updates that are released.

If attendees are not able to join the event live on the day of the conference, an archived webcast will also be made available on EmergingGrowth.com and on the Emerging Growth YouTube Channel, View Source We will release a link to that after the event.