On July 9, 2023 RemeGen Co., Ltd. ("RemeGen" or "the Company") (HKG: 9995, SHA: 688331), a fully-integrated commercial-stage biotechnology company, reported a clinical research and supply agreement with Innovent Biologics ("Innovent") (HKEX: 01801) (Press release, RemeGen, JUL 9, 2023, https://www.prnewswire.com/news-releases/remegen-and-innovent-collaborate-on-clinical-trials-to-evaluate-the-potential-of-rc88-and-rc108-combined-with-pd-1-therapy-for-advanced-solid-tumors-301872574.html [SID1234633146]). This collaboration will focus on conducting clinical trials exploring combination therapies of the novel antibody-drug conjugates (ADCs), RC88 (targeting MSLN) and RC108 (targeting c-MET), along with the PD-1 inhibitor sintilimab injection (TYVYT).

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According to the agreement, Innovent will supply clinical drug supplies of sintilimab during the clinical trial collaboration, while RemeGen will conduct Phase I/IIa clinical studies in China. The trials will assess the safety, tolerability, and preliminary efficacy of RC88 or RC108 combined with sintilimab in Chinese cancer patients.

RemeGen’s independently developed ADC, RC88, targets mesothelin (MSLN) and was approved for Phase I clinical trials in China in November 2018. Preliminary results show that RC88 monotherapy exhibits anti-tumor activity against MSLN-expressing solid tumors and demonstrates manageable safety. The combined use of RC88 with immune checkpoint inhibitors (ICIs) such as PD-1/PD-L1 can induce immunogenic cell death (ICD), releasing a series of signaling molecules to further activate T cells, and enhancing the tumor immune response.

Similarly, RC108, another ADC independently developed by RemeGen targeting c-MET, was approved for Phase I clinical trials in November 2020. The ongoing trials indicate the potential of RC108 monotherapy against c-MET-expressing solid tumors, with manageable safety. Preclinical research suggests that RC108 induces tumor-specific adaptive immunity and increases T cell infiltration in the tumor microenvironment, while PD-1 monoclonal antibodies activate T cells, enhancing the anti-tumor immune response. Therefore, it is expected that the combination therapy of RC108 and TYVYT can enhance both the presentation of tumor antigens by dendritic cells and the killing of tumor cells by T cells, resulting in enhanced tumor suppression.

TYVYT, a PD-1 inhibitor developed collaboratively by Innovent and Eli Lilly and Company (NYSE: LLY), has been approved for seven indications, six of which have been included in China’s National Reimbursement Drug List (NRDL). It is the only PD-1 inhibitor to include first-line treatment for the five major high-incidence solid tumors (non-squamous non-small cell lung cancer, squamous non-small cell lung cancer, liver cancer, gastric cancer, esophageal cancer), and also the first and only immunotherapy drug in the field of gastric cancer to be included in the NRDL.

"The alliance with Innovent is a critical step forward in the research and commercialization strategy of combination therapies with RC88 and RC108," said Su Na, Senior Vice President of RemeGen. "By combining these therapies with sintilimab, we offer innovative treatment plans that target two pathways. These mechanisms are complementary, potentially helping to overcome or delay treatment resistance and provide an effective solution to unmet clinical needs."

"We are thrilled to join forces with RemeGen to unlock the potential of combining sintilimab injection with novel ADCs," added Dr. Zhou Hui, Senior Vice President of Innovent. "Preclinical studies have suggested that combining ADCs with an anti-PD-1 monoclonal antibody may improve patient outcomes and overcome drug resistance. As immunotherapy advanced into the next era of development, we hope to strengthen the leading position of sintilimab as a backbone immunotherapy as well as investigate the new opportunities of combination therapies, and provide better treatment options for more cancer patients."

On July 8, 2023 Tyligand Bioscience reported the completion of a multimillion-dollar Series A+ financing (Press release, Tyligand Bioscience, JUL 8, 2023, View Source [SID1234644985]). This round was led by Ming Ventures, with participation from Taikun Fund, Suzhou Harvicapital, Shengdi Investment, and Calor Capital as co-investors. Existing shareholders CMS Capital and BOHE Angel Fund also increased their stake. The capital raised will primarily be used to accelerate the advancement of multiple projects in Tyligand’s innovation pipeline, including clinical trials in both US and China.

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Tyligand Bioscience is dedicated to discovering and developing highly differentiated small molecule therapies to provide more effective treatment options for drug resistant tumors include lung, pancreatic, and triple-negative breast cancers. The founding team has a strong track record in the field of small molecule drug discovery and development, and has a wealth of management and operational experience in multinational pharmaceutical companies as well as emerging biotechs. The company focuses on addressing unmet clinical needs with structurally intriguing small molecules and their conjugates, with several candidates having entered into clinical stage development. TSN084, a multi-kinase inhibitor targeting CDK8/19 and other kinases closely associated with tumor proliferation and immune suppression, is currently undergoing Phase I clinical trials in both US and China and has recently received FDA orphan drug designation for treating AML. With the prevailing trend in the kinase field moving towards highly selective inhibitors against a single target, the excellent tolerability and ability of TSN084 to launch a multi-targeted attack provide possibilities to address drug resistance and immune evasion. TSN222 is a global 1st dual-acting tumor immune agonist (DATIA) with differentiated design from traditional immune agonists. Preclinical data indicated that TNS222 was capable of sequentially activating the innate immune system and selectively killing tumors, thereby leading the establishment of durable adaptive immune memory and controlling the proliferation of distal tumors. This compound has also received approval for clinical trials in both US and China. Additionally, Tyligand has demonstrated the effectiveness of DATIA series of molecules as payloads for antibody-drug conjugates, and has attracted multiple collaborators.

Dr. Tony Zhang, founder and CEO of Tyligand, stated, "We are extremely grateful for the support from Ming Ventures and co-investors. This round of support not only serves as an encouragement to the Tyligand team but also as a recognition of the differentiated pipeline built from the Tyligand’s on unique molecule design platform. We will continue to push forward the pipeline with utmost efficiency and creativity, making medicines with greater clinical value for the waiting doctors and patients."

Ming Venture stated, "We are honored to lead this round of financing for Tyligand Bioscience. Innovative drugs are a key investment focus for Ming Venture, and we continue to have a positive outlook on the oncology area. This field has significant umet clinical needs and growing market potential, and every progress can genuinely help alleviate patients’ suffering. Core members of Tyligand’s team have years of extensive R&D management experience and are a trustworthy team. The company has a clear strategic vison, strong execution, and great capital utilization efficiency, having completed the preclinical development of three products in record time. The unique approach of dual-function immune agonism by small molecules offers key advantages in immunoncology field, and we look forward to benefiting global cancer patients with these innovative products as soon as possible."

On July 7, 2023 Huihe Biotechnology (CytoCares) reported that the company cooperated with the Hematology Hospital of the Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) (hereinafter referred to as the Institute of Hematology) (Press release, CytoCares, JUL 7, 2023, View Source;mid=2247484650&idx=1&sn=9a1343eccfaf5258fa9ca7674b70adcd&chksm=ec9976b5dbeeffa3a5b91740f2bfd72d4ba5f3e748ac24ceaf6b0fbd81a840e487be514fdc23&token=220933712&lang=zh_CN#rd [SID1234635270]). A study to evaluate the safety tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and preliminary anti-tumor activity of CC312 in adult patients with relapsed/refractory CD19-positive B-cell hematological malignancies The launch meeting of "Multi-center Phase I Clinical Research" was held in the conference room of the Phase I Ward Building, Building C of the Blood Institute. The Phase I research team led by Professor Qi Junyuan and Huihe Biotech CEO Mr. Huang Yingfeng and Huihe Biotech’s clinical team attended this meeting.

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CC312 freeze-dried powder injection (Biological Products for Therapeutic Use Category 1) is the first blockbuster drug of T cell activation platform independently developed by Huihe Biotechnology. It is a drug that targets B cell surface antigen CD19, T cell antigen CD3 and T cell co- Recombinant trispecific T-cell engager (TriTE ) based on the stimulatory molecule CD28. CC312 can form a bridge between tumor cells (B cells) and T cells, and coordinately regulates T cells by activating the CD3 signaling pathway of T cells and the costimulatory signal CD28 pathway, inducing long-lasting and sustained T cell activation, making T cells Kill tumor cells more effectively. Preclinical studies have shown that CC312 exhibits significant anti-tumor activity in tumor cell lines expressing CD19 antigen, and is expected to provide better treatment options for patients with CD19+ refractory/relapsed B-cell malignancies. In addition, preclinical safety data indicate that CC312 is well tolerated in Hu-HSC mice and cynomolgus monkeys, and no administration-related toxicological abnormalities were observed in histopathological studies.

This study will recruit patients with relapsed/refractory CD19-positive non-Hodgkin lymphoma (NHL), including indolent and aggressive B-cell NHL, to evaluate the safety and tolerability of CC312 in this population; explore the dose limitations of CC312 toxicity (DLT), and determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D).

Hematology Hospital, Institute of Hematology, Chinese Academy of Medical Sciences Graduated from Shandong Medical University in 1990. He has done basic medical research abroad for 5 years. In 2005, he returned to the Hematology Hospital (Institute of Hematology), Chinese Academy of Medical Sciences and has been working ever since. Currently working in the new drug clinical trial ward of the hospital, he is mainly engaged in the diagnosis and treatment of blood diseases and new drug clinical trials. He is good at the diagnosis and identification of hematological diseases, as well as the individualized overall treatment of hematological tumors (including lymphoma, myeloma, leukemia, etc.).

At the kick-off meeting, PI Professor Qi Junyuan’s team and Huihe’s clinical team discussed and exchanged information on the "CC312-001 Project Clinical Plan". The discussion was lively and the participating experts actively had in-depth discussions and reached consensus on the protocol design, primary endpoints of the study, inclusion criteria, patient screening and other aspects.

Currently, except for Sanofi’s two tertiary antibodies based on dual-signal activation of T cells, there are no clinical reports of dual-signal-activated T-cell-related tertiary antibodies in China. The launch of Huihe Biotech’s CC312 clinical project hopes to effectively help patients with relapsed/refractory CD19-positive non-Hodgkin lymphoma (NHL) reduce their pain and restore health.

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.