1stOncology™: Cancer Intelligence Service – Page 747 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Carisma Therapeutics to Participate in the 7th Annual Evercore ISI HealthCONx Conference

On November 27, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that Steven Kelly, President and Chief Executive Officer, will participate in a fireside chat at the 7th Annual Evercore ISI HealthCONx Conference on Thursday, December 5th at 9:35 am ET (Press release, Carisma Therapeutics, NOV 27, 2024, https://www.prnewswire.com/news-releases/carisma-therapeutics-to-participate-in-the-7th-annual-evercore-isi-healthconx-conference-302316979.html [SID1234648690]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

An audio webcast of the event will be available on the Company’s Investor Events section of the Investor Relations webpage and will be archived for a limited time following the event.

Kelun-Biotech’s TROP2 ADC Sacituzumab tirumotecan (sac-TMT) Approved For Marketing By NMPA Of China For 2L+ Advanced or Metastatic TNBC

On November 27, 2024 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the Company received marketing authorization in China from National Medical Products Administration (NMPA) for the first domestically developed trophoblast cell-surface antigen 2 (TROP2)-directed antibody–drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870) for adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) (Press release, Kelun, NOV 27, 2024, View Source [SID1234648689]). This is the first domestically developed TROP2 ADC approved for marketing in China and the first domestically developed ADC fully approved for marketing in China.

The approval is based on the positive results from a randomized, controlled, phase 3 OptiTROP-Breast01 study in adult patients with unresectable locally advanced or metastatic TNBC who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting). Sac-TMT demonstrated statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) compared to chemotherapy. The results were presented at the special clinical science symposium for next-generation ADCs at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in May 2024.

Previously, NMPA has accepted two supplemental new drug applications (sNDA) seeking the approvals of sac-TMT monotherapy for the treatment of patients with locally advanced or metastatic EGFR-mutant non-small cell lung cancer (NSCLC) following progression on EGFR-TKI therapy only, or both EGFR-TKI and platinum-based chemotherapy, respectively.

Dr. Micheal Ge, CEO of Kelun-Biotech said, "It is a great pleasure to share with you the important milestone moment of the successful approval and launch of sacituzumab tirumotecan in China, which is a significant achievement of Kelun-Biotech’s years of deep-rooted source innovation. As the company’s first proprietary TROP2 ADC innovative drug, the successful launch of sacituzumab tirumotecan officially opens up a new pattern for the treatment of patients with 2L+ advanced TNBC. We expect that its excellent clinical efficacy and safety results will significantly enhance the clinical benefits and improve the quality of life of patients with advanced TNBC. In the future, we will continue to explore the clinical value of sacituzumab tirumotecan in other indications, maximize the market potential of sacituzumab tirumotecan, and satisfy the clinical needs of patients nationwide."

ABOUT MARKET VALUE

Breast cancer is a threat to women’s lives and health. Among them, triple-negative breast cancer has unique biological behavioral characteristics, and is also known as the "most toxic" breast cancer. 2022 analysis of China’s malignant tumor epidemiology data shows that there are 357,000 new cases of breast cancer and 75,000 deaths in Chinese women annually [1]. In the absence of effective therapeutic targets for triple-negative breast cancer, chemotherapy is the most important systemic treatment in the clinic [2], but it often has poor efficacy and high toxicity and side effects, and the prognosis is different from other subtypes of breast cancer [3], it is vital to explore more therapeutic means to improve the clinical benefit.

ABOUT sac-TMT

Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

Syndax Announces Participation at the Citi 2024 Global Healthcare Conference

On November 27, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that Michael A. Metzger, Chief Executive Officer of Syndax, will participate in a panel discussion on novel mechanisms in oncology at the Citi 2024 Global Healthcare Conference on Thursday, December 5, 2024 at 11:00 a.m. ET (Press release, Syndax, NOV 27, 2024, View Source [SID1234648688]).

A live webcast of the panel can be accessed from the Investor section of the Company’s website at www.syndax.com, where a replay will also be available for a limited time.

Sensei Biotherapeutics to Participate in Citi’s 2024 Global Healthcare Conference

On November 27, 2024 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage biotechnology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported that Company management will participate in Citi’s 2024 Global Healthcare Conference, being held on December 3-5, in Miami, FL (Press release, Sensei Biotherapeutics, NOV 27, 2024, View Source [SID1234648687]).

SELLAS Announces Positive Data from Preclinical Studies Indicating ASXL1 Mutations as Predictor of Response to SLS009 in Solid Cancers

On November 27, 2024 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported data from preclinical studies identifying ASXL1 mutation as key predictor of SLS009, a highly selective CDK9 inhibitor, response in solid cancers (Press release, Sellas Life Sciences, NOV 27, 2024, View Source [SID1234648686]).

Based on elucidated biology of ASXL1 mutations, results from SELLAS’ clinical trials in acute myeloid leukemia (AML), and reports of common occurrence of ASXL1 mutations in some solid cancers, the Company performed experiments and analyses to explore the following:

The frequency of ASXL1 mutations in certain solid cancers, including colorectal carcinomas (CRC) with high level microsatellite instability (MSI-H) and non-small cell lung cancer (NSCLC)
Whether ASXL1 mutations in solid cancers may predict as high SLS009 efficacy as the efficacy exhibited in AML where ASXL1 and similar mutations demonstrated high response rates in SELLAS’ clinical trials
SELLAS performed experiments in patient derived cell lines (PDCs) exposing them to SLS009 at various concentrations and determining the inhibitory concentration (IC50) for each cell line. All cell lines were analyzed for presence of ASXL1 mutations and other genetic markers. High efficacy was prespecified as IC50 < 100 nM, significantly lower than the standard threshold definition for an effective compound (IC50 < 1,000 nM). This threshold was chosen based on the observed long-lasting concentrations of SLS009 observed in patients, which were ~400 nM.

Negative controls consisted of untreated cell lines, while active negative control varying concentrations of revumenib (drug used in hematologic malignancies). Positive controls involved cell lines treated with staurosporine at different concentrations (staurosporine is a standard control compound for kinase inhibitors due to its high broad-spectrum potency in inhibiting most protein kinases at sub-micromolar concentrations).

The results were as follows:

In CRC MSI-H, ASXL1 mutations were observed in 7/12 (58%) of PDCs, aligning with predicted frequency of ~55%
In NSCLC, ASXL1 mutations occurred in 2/6 (33%) studied cell lines, higher than predicted 2.6%
Overall, in 18 studied solid cancer cell lines, ASXL1 mutations were recorded in 9 cell lines and no ASXL1 mutations were recorded in 9 cell lines which were designated as control
In ASXL1 mutated cell lines, high SLS009 efficacy (IC50 <100 nM) was observed in 6/9 (67%) solid cancer cell lines and in non-ASXL1 mutated cancer high SLS009 efficacy was observed in 0/9 (0%) of studied solid cancer cell lines
In CRC MSI-H, high efficacy (IC50 <100 nM) was observed in 4/7 (57%) of ASXL1 mutated cell lines and in 0/5 (0%) of non-ASXL1 mutated cell lines
In NSCLC, high efficacy (IC50 <100 nM) was observed in 2/2 (100%) of ASXL1 mutated cell lines and in 0/4 (0%) of non-ASXL1 mutated cell lines
No activity was observed in any of the studied cell lines with revumenib (negative control) at any concentration
Staurosporine activity was confirmed, but interestingly and importantly, SLS009 outperformed positive control staurosporine in 5/9 cell lines
"These findings are incredibly encouraging and validate our approach to developing a targeted solid tumor therapy. We are excited that our hypotheses were confirmed, marking, to the best of our knowledge, the first study to advance the identification of ASXL1 mutations as a potential biomarker for a drug response in solid cancers," said Dr. Dragan Cicic, Senior Vice President, Chief Development Officer at SELLAS. "Our experiments show that SLS009 demonstrates high efficacy with low IC50 values and with 67% of mutated cell lines responding positively, compared to no response in non-mutated cell lines. In addition, SLS009 outperformed positive control in 5 out of 9 cell lines, establishing itself as a highly effective therapeutic candidate. These critical findings are the missing pieces, complementing our existing safety and efficacy data in AML, and positions us strongly with SLS009 in solid cancers."

SELLAS has filed for provisional patent protection for the use of ASXL1 mutations as predictive diagnostic for selection of cancer patients likely to benefit based on clinical data and biology.