On March 10, 2024 RemeGen Co. Ltd.("RemeGen" or "the Company") (9995.HK, 688331.SH), a commercial-stage biotechnology company, reported an oral presentation on an interim analysis of the evaluation of the Company’s proprietary Disitamab Vedotin (RC48), an investigational anti-HER2 antibody-drug conjugate (ADC) targeting prevalent solid tumor cancers with significant unmet medical needs, at the European Congress on Gynaecological Oncology (ESGO 2024 Congress) held in Barcelona from March 7-10, 2024 (Press release, RemeGen, MAR 10, 2024, View Source [SID1234640983]).

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A Phase II, open-label, multicenter basket design study (NCT04965519) is currently underway to evaluate the effectiveness and safety of RC48 monotherapy in the treatment of HER2-expressing gynecologic malignancies. The cervical cancer cohort includes patients with recurrent or metastatic cervical cancer who have progressed on at least 1L anti-tumor therapy and have HER2 IHC ≥1+. The treatment regimen consists of RC48 monotherapy administered at a dose of 2 mg/kg Q2W. The primary endpoint is objective response rate (ORR) by Independent Review Committee, with secondary endpoints including ORR by Investigator, duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety.

As of October 31, 2023, 25 patients with cervical cancer were enrolled with a median age of 56 years (range: 35-66). Most patients (64%) had a baseline ECOG performance score of 1. 18 patients had a primary FIGO stage of IIB or higher. 16 (64%) patients had squamous cell carcinoma, and 9 (36%) had adenocarcinoma. Among the 22 efficacy evaluable patients,

The ORR was 36.4% (8/22). The confirmed ORR was 31.8% (7/22), the DCR was 86.4% (19/22), and the median time to response was 1.5 months.
The mDoR was 5.52 months, and the mPFS was 4.37 months.
The most common treatment-related adverse events (TRAEs) included an increase in ALT (56%), an increase in AST (56%), and a decrease in white blood cell count (52%). Two patients (8%) experienced SAEs, and there were no deaths related to RC48. In conclusion, RC48 demonstrates a manageable safety profile and positive efficacy in HER2-expressing r/m cervical cancer patients, suggesting it to be a promising new treatment for HER2-expressed cervical cancer.

Dr. Jianmin Fang, CEO of RemeGen, commented, "ESGO congress is a unique opportunity for professionals from around the world to share and discuss their latest medical and scientific developments in their gynecological cancers research, treatment, and care. I am delighted to share an oral presentation on the evaluation of our proprietary ADC Disitamab Vedotin at ESGO 2024. It marks RemeGen’s commitment to continued innovation and advancement in the field of cervical cancer treatment, and we strongly believe that the results of RC48 will bring new hope to cervical cancer patients."

Cervical cancer is one of the most common gynecological malignancies, with the latest cancer report in China in 2022 showing the 5-year progression-free survival (PFS) rate of patients with late-stage recurrent or metastatic cervical cancer to be only about 15%. Current treatment options for patients with recurrent or metastatic cervical cancer are limited to immunotherapy and chemotherapy (ORR ranging from 14.6% to 26.8%), indicating there are significant unmet clinical needs.

On March 8, 2024 Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences Inc., a global fully-integrated clinical-stage biotech company, reported that Nature Communications – peer-reviewed, open access, scientific journal – published a manuscript describing the pre-clinical development of ISB 1442, a CD38 and CD47 Bispecific Biparatopic Antibody Innate Cell Modulator (online manuscript available here) (Press release, Ichnos Sciences, MAR 8, 2024, View Source;utm_medium=rss&utm_campaign=ichnos-glenmark-innovation-reports-the-publication-in-nature-communications-of-the-preclinical-development-of-isb-1442-bispecific-antibody-for-treatment-of-relapsed-refractory-multiple-myeloma [SID1234642877]). ISB 1442 is currently being tested in a Phase I clinical trial in relapsed refractory multiple myeloma.

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"The acceptance of our manuscript by Nature Communications signifies the high quality of research conducted at Ichnos Glenmark Innovation, particularly in the challenging field of multiple myeloma. Our ongoing Phase I trial is a testament to our commitment to advancing care for patients battling this complex disease. We are eager to present further data to the medical community before the end of this year, highlighting our continuous efforts to innovate and improve patient outcomes," said Cyril Konto, President, CEO and Board Member of Ichnos Glenmark Innovation.

ISB 1442 is a multispecific antibody, rationally designed to harness innate immunity to treat CD38+ hematologic malignancies. ISB 1442 antibody is unique due to three features: (i) it uses two distinct Fab arms to target the CD38 tumor associated antigen (biparatopic approach), allowing for improved Complement Dependent Cytotoxicity (CDC) and improved binding to tumor cells when an antigen is downregulated; (ii) it blocks the CD47 ‘don’t eat me’ signal to counteract tumor escape from phagocytosis, leveraging selective avidity-induced binding to CD38+ tumor cells, thereby avoiding off-tumor targeting; and (iii) it is equipped with the Fc mutations enhancing effector mechanisms (CDC, Antibody Dependent Cell Cytotoxicity and Antibody Dependent Cell Phagocytosis).

The flexibility of the BEAT(Bispecific Engagement by Antibodies based on the TCR) platform enabled straightforward integration of all these features into a single antibody molecule.

Impactful pre – clinical study outcome
On cell lines, ISB 1442 showed superior tumor cell killing against daratumumab or to the combination of daratumumab with an anti-CD47 mAb (hu5F9). This implies that the engineering and architecture of ISB 1442 possesses improved effector functions compared to standard anti-CD38 monoclonal antibodies as well as their combination with CD47 blocking agents.

ISB 1442 consistently demonstrated superior tumor growth inhibition compared to daratumumab in preclinical mouse models in vivo and higher killing of tumor cells in primary multiple myeloma patient’s samples ex vivo, including in patients that relapsed from anti-CD38 therapies. This suggests that ISB 1442 could be effective as monotherapy as well as salvage therapy. Altogether, ISB 1442 may represent an improved therapeutic option available for the treatment of multiple myeloma patients relative to other monospecific anti-CD38 antibodies.

On March 8, 2024 Agendia, Inc., reported that it will share new data from the ongoing prospective, observational FLEX Trial (NCT03053193) in two poster presentations at the 41st Annual Miami Breast Cancer Conference (MBCC), taking place March 7 – 10th, 2024 (Press release, Agendia, MAR 8, 2024, View Source [SID1234640976]).

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The first poster, titled MammaPrint and BluePrint predict anthracycline chemosensitivity in patients with HR+HER2-early-stage breast cancer enrolled in FLEX, (Audeh, W., et al.), investigates the associations between MammaPrint and BluePrint classifications, therapy regimen, and the likelihood of achieving a pathologic Complete Response (pCR). Researchers looked at patients who had hormone receptor-positive (HR+), Human Epidermal Growth Factor Receptor (HER) 2-negative early-stage breast cancer – categorized as MammaPrint High Risk – who had been treated with either a combination of two (taxane and cyclophosphamide, TC) or three (TC with anthracycline, AC-T) types of neoadjuvant chemotherapy. Patients were then further stratified into MP High 1 and High 2 categories, and further stratified by BluePrint subtype of Luminal and Basal. Results showed that patients with MP High 2 tumors, including Luminal B and Basal subtypes, are more likely to achieve a pCR in response to AC-T, while the addition of anthracycline to the therapy regimen does not appear to improve pCR rates for patients with MP High 1, Luminal B-type tumors.

The second poster, titled Prediction of chemotherapy benefit by MammaPrint in patients with HR+HER2-early-stage breast cancer from real-world evidence studies (Audeh, W., et al.), used data from patients with HR+ HER2-negative early-stage breast cancer enrolled in the FLEX and NBRST trials to generate a prediction of the magnitude of chemotherapy benefit based upon a patient’s genomic risk, looking at the MammaPrint index more closely as a continuous variable. Researchers examined the association of the MammaPrint index with benefit from chemotherapy by evaluating two clinical endpoints, the likelihood of pCR in response to neoadjuvant chemotherapy, and the five-year outcome among patients who received chemotherapy and endocrine therapy or endocrine therapy alone.

Consistent with results found in the landmark MINDACT trial, this study showed that the MammaPrint index demonstrates strong efficacy in predicting low chemosensitivity in Low Risk and Ultra Low Risk tumors, reinforcing that these groups do not derive significant chemotherapy benefit. However, it was also observed that chemotherapy effectiveness increased as MammaPrint risk increased in High 1 and High 2 tumors, as evidenced by both pCR rates and 5-year outcomes, demonstrating that the overall benefit of chemotherapy increases as MammaPrint risk increases. Taken together, these findings indicate the utility of MammaPrint to predict neoadjuvant and adjuvant chemotherapy benefit in this patient population.

"In this unique real world evidence FLEX study, we were able to look at chemosensitivity for patients who had received neoadjuvant treatment and the chemo benefit for patients who are treated with systemic therapy after surgery, showing that MammaPrint is predictive of chemotherapy benefit in both cases. The FLEX Trial, with over 16,000 women enrolled, is now allowing us to look at clinical outcomes as well as analyzing whole transcriptome data," said William Audeh, MD, MS, Chief Medical Officer of Agendia. "The data we’re sharing at the Miami Breast Cancer Conference confirms that gene expression profiling with these assays identify who may benefit from chemotherapy, and may prove helpful in regimen selection as well. We look forward to further exploring the capabilities of MammaPrint and BluePrint for women across the entire spectrum of breast cancer risk and subtype."

The goal of Agendia’s research is to increase the likelihood of managing each individual’s cancer diagnosis by delivering a customized treatment plan to the patients most likely to benefit based on the unique features of their tumor.

On March 8, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that it will share data across its dermatologic portfolio of gene expression profile (GEP) tests via oral and electronic poster presentations at the 2024 AAD Annual Meeting, taking place March 8-12 in San Diego (Press release, Castle Biosciences, MAR 8, 2024, View Source [SID1234640975]).

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"Our presentations at the 2024 AAD Annual Meeting add to the growing body of evidence supporting the use of our tests in guiding improved, personalized care for patients with skin cancers," said Robert Cook, Ph.D., senior vice president of research and development at Castle Biosciences. "In collaboration with leading dermatologists dedicated to advancing patient care, we are excited to share our latest findings which highlight how our tests are empowering both clinicians and patients with meaningful, clinically actionable information that can refine risk and inform important treatment decisions."

Castle will present the following abstracts at AAD. Abstract content will be available throughout the meeting in the online viewing portal and at the on-site viewing stations, and will also be published online in the Fall 2024 Journal of the American Academy of Dermatology (JAAD) supplement.

DecisionDx-Melanoma

Oral Poster Presentation Title: 31-GEP testing is associated with improved melanoma-specific survival relative to untested patients: an analysis of patients <65 years old
Presenter and Lead Author: Michael Tassavor, M.D., Skin Cancer Center, Cincinnati
Abstract Number: 51667
Date: March 9, 2024
Time: 4:50-4:55 p.m. Pacific Time
Location: San Diego Convention Center (Upper Level, Sails Pavilion, Poster Center 1)
Summary: For patients with CM, the median age at diagnosis is 66 years old, suggesting that almost half of newly diagnosed patients are younger than 65. In this large study of unselected, clinically tested patients with CM who were under 65 (n=5,183), the DecisionDx-Melanoma (31-GEP) test identified patients at higher risk of melanoma-specific death who may benefit from more aggressive management, including imaging surveillance. In the study, use of the DecisionDx-Melanoma test was associated with improved melanoma-specific survival relative to untested patients. This is clinically significant, as identifying high-risk patients allows for earlier detection of recurrence, while the tumor burden is lower, which has been shown to lead to better response to therapy.

DecisionDx-SCC

Oral Poster Presentation Title: Consistent utilization of the 40-gene expression profile (40-GEP) test in high-risk cutaneous squamous cell carcinoma (cSCC) by clinicians according to intended use indications
Presenter and Lead Author: Jane Yoo, M.D., Icahn School of Medicine at Mount Sinai, New York
Abstract Number: 54153
Date: March 9, 2024
Time: 10:30-10:35 a.m. Pacific Time
Location: San Diego Convention Center (Upper Level, Sails Pavilion, Poster Center 2)
Summary: This study provides summary metrics regarding DecisionDx-SCC (40-GEP) test results and patient risk factors for tumor samples clinically tested in the first three years of the test’s availability between September 2020 and August 2023 (n=16,930). The study data demonstrate that clinicians are utilizing the DecisionDx-SCC test appropriately for patients with high-risk cutaneous squamous cell carcinoma (SCC). These patients are at a higher risk of poor outcomes compared to the general SCC patient population, yet over 70% of patients received a Decision-SCC Class 1 test result, indicating they are at a lower biological risk for metastasis. Each DecisionDx-SCC Class result was present in the various subgroupings of risk factors in the study (patients with 1-2, 3-4 and more than 5 risk factors), demonstrating that the test provides independent risk assessment from clinicopathological presentation. These data support incorporating the test’s results into clinical practice to improve the accuracy of risk predictions to guide more personalized treatment plans for patients.

MyPath Melanoma

ePoster Title: Enabling access to prognostic gene expression profile (GEP) testing for invasive melanoma by leveraging RNA-based testing in the diagnostic workflow
Abstract Number: 52819
Summary: Reaching a definitive diagnosis of melanoma can be challenging. Ancillary testing can provide clarity and a definitive diagnosis for problematic lesions. The MyPath Melanoma (23-GEP) diagnostic test returns accurate results quickly, with approximately 80% of cases tested receiving an actionable result in a median of four business days. Between March 1 and July 31, 2023, approximately 60% of ambiguous lesions tested with MyPath received a benign test result, potentially reducing overdiagnosis and overtreatment for diagnostically challenging lesions. Lesions that receive a malignant test result (approximately 20% of lesions tested with MyPath in the five-month study timeframe) can be tested with the DecisionDx-Melanoma risk stratification test, using the same extracted tumor material when available, to inform risk-aligned decisions about sentinel lymph node biopsy, surveillance imaging and patient follow-up schedules. Approximately 80% of clinically tested lesions with a malignant MyPath result have sufficient biopsy tumor content for DecisionDx-Melanoma testing.

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 50 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through Dec. 31, 2023, DecisionDx-Melanoma has been ordered more than 150,000 times for patients diagnosed with cutaneous melanoma.

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 (higher) or Class 2B (highest) 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 MyPath Melanoma

MyPath Melanoma is Castle’s gene expression profile test designed to provide an accurate, objective result to aid dermatopathologists and dermatologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately two million suspicious pigmented lesions biopsied annually in the U.S., Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. For these cases, the treatment plan can also be uncertain. Obtaining accurate, objective ancillary testing can mean the difference between a path of overtreatment or the risk of undertreatment. Interpreted in the context of other clinical, laboratory and histopathologic information, MyPath Melanoma is designed to reduce uncertainty and provide confidence for dermatopathologists and help dermatologists deliver more informed patient management plans.

On March 8, 2024 TransThera, a clinical-stage biopharmaceutical company dedicated to innovating differentiated drugs globally, reported that the randomized, controlled, global multicenter Phase 3 trial (FIRST-308) of tinengotinib versus physician’s choice to evaluate the efficacy and safety in subjects with FGFR-altered, chemotherapy- and FGFR Inhibitor-refractory/relapsed cholangiocarcinoma (CCA), has been authorized by regulatory agencies in the European Union (EU) after the authorizations from US, South Korea and Taiwan region (Press release, TransThera Biosciences, MAR 8, 2024, View Source [SID1234640974]). Furthermore, European Medicines Agency (EMA) granted the Orphan Drug Designation(ODD) for tinengotinib for the treatment of biliary tract cancer (BTC) .

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Tinengotinib, a next-generation FGFR inhibitor with high potency against a variety of FGFR2 kinase domain mutations, has shown promising clinical benefit in subjects with FGFR-altered metastatic CCA who were heavily pretreated with chemotherapy and refractory/relapsed to FGFRi(s). The results of tinengotinib in CCA from the phase I/II clinical trials were presented orally at 2023 ESMO (Free ESMO Whitepaper) and 2024 ASCO (Free ASCO Whitepaper) GI conferences. The FRIST-308 clinical trial is enrolling to further confirm the efficacy and safety of tinengotinib in CCA. In December 2023, first patient was dosed in the United Sates (US).

"We are very delighted to have achieved the significant regulatory progresses for tinengotinib in global development at various countries and regions. These milestones are not only the recognition by global regulatory authorities of the potential clinical benefit of tinengotinib to treat CCA patients, but also a reflection of the company’s international regulatory capabilities and unwavering commitment to bringing innovative therapies to global patients," said Jean Fan, M.D., Chief Medical Officer of TransThera Sciences. "Leveraging the regulatory agency’s support from the EU in addition to the US and other countries and regions, we will continue to expedite the global clinical development and commercialization of tinengotinib. We are hopeful that these efforts will enable us to bring this novel drug to patients around the world as quickly as we can."

About ODD in EU

The term "orphan medicines" refers to pharmaceutical products developed for the prevention, diagnosis, and treatment of rare diseases or conditions affecting less than 5 in 10,000 people in the EU. The EMA offers a range of incentives to encourage the development of designated orphan medicines. This Orphan Drug Designation for tinengotinib qualifies it for great regulatory supports in the subsequent clinical development and commercialization in the EU, including protocol assistance, fee reductions, and most importantly, 10 years of market exclusivity upon approval.

About tinengotinib

Tinengotinib is an innovative, global phase III stage spectrum-selective kinase inhibitor that exerts antitumor effects by targeting tumor cells proliferation, angiogenesis and immune-oncology pathways by inhibiting the cytokine signaling and angiogenesis (FGFRs and VEGFRs), mitotic kinases Aurora A/B and Janus kinases (JAK). Ongoing clinical trials in the US and China have revealed the potential of tinengotinib to be efficacious in various solid tumors. It was granted the Orphan Drug Designation and Fast Track Designation by the FDA for the treatment of CCA. In July 2023, tinengotinib was granted the Breakthrough Therapy Designation (BTD) by NMPA in China. In March 2024, tinengotinib was granted the Orphan Drug Designation(ODD) for the treatment of biliary tract cancer by EMA.