Khaled Ibrahim’s Post

Journal of Chemotherapy - Special Collection Invitation - Protein Kinase Inhibitors for Targeted Cancer Therapy - Reminder Dear Colleagues,    As a Guest Co-Editor, I renew my invitation to you to submit a review or research manuscript of yours to the special collection entitled “Protein Kinase Inhibitors for Targeted Cancer Therapy” in Journal of Chemotherapy.   While a wide range of different protein kinase inhibitors is available in clinical oncology practice and remarkable clinical success has been achieved with their use, limitations in the field remain and further discovery as well as in depth biological comprehension of their mechanisms of action and resistance is needed.   The editors of Journal of Chemotherapy aim to stimulate discussion on the discovery, development, and clinical applications of protein kinase inhibitors through a curated collection of high-quality reviews and original research articles.   Articles submitted to the collection will be assessed and peer reviewed per regular journal processes. More information on the scope of the collection can be found at this link:   http://bit.ly/3QrcZdl    or on the journal website (https://lnkd.in/dtPGeZkD).  Please note this is an Open Access collection. You may find information on benefits of OA publishing with JOC at: https://lnkd.in/dj2fwGDn   The deadline for manuscript submission has been updated and extended to 31 December 2024.   I hope you will consider publishing in this collection and contributing to build a higher impact journal together with other distinguished scientists from all the countries!   If you have any questions about the collection scope or the appropriateness of your contribution, please reach out.   Best regards,   Enrico Mini M.D., Ph.D. Guest Co-Editor Special Collection “Protein Kinase Inhibitors for Targeted Cancer Therapy” Journal of Chemotherapy #proteinkinaseinhibitors #targetedcancertherapy #drugdiscovery #drugdevelopment #clinicaltrials #pharmacology #toxicology #pharmacogenomics #pharmacokinetics #tumordrugresistance #pharmacovigilance #pharmacoeconomics

Journal of Chemotherapy - Special Collection Invitation - Protein Kinase Inhibitors for Targeted Cancer Therapy - Reminder Dear Colleagues,    As a Guest Co-Editor, I renew my invitation to you to submit a review or research manuscript of yours to the special collection entitled “Protein Kinase Inhibitors for Targeted Cancer Therapy” in Journal of Chemotherapy.   While a wide range of different protein kinase inhibitors is available in clinical oncology practice and remarkable clinical success has been achieved with their use, limitations in the field remain and further discovery as well as in depth biological comprehension of their mechanisms of action and resistance is needed.   The editors of Journal of Chemotherapy aim to stimulate discussion on the discovery, development, and clinical applications of protein kinase inhibitors through a curated collection of high-quality reviews and original research articles.   Articles submitted to the collection will be assessed and peer reviewed per regular journal processes. More information on the scope of the collection can be found at this link:   http://bit.ly/3QrcZdl    or on the journal website (https://lnkd.in/dtPGeZkD).  Please note this is an Open Access collection. You may find information on benefits of OA publishing with JOC at: https://lnkd.in/dj2fwGDn   The deadline for manuscript submission has been updated and extended to 31 December 2024.   I hope you will consider publishing in this collection and contributing to build a higher impact journal together with other distinguished scientists from all the countries!   If you have any questions about the collection scope or the appropriateness of your contribution, please reach out.   Best regards,   Enrico Mini M.D., Ph.D. Guest Co-Editor Special Collection “Protein Kinase Inhibitors for Targeted Cancer Therapy” Journal of Chemotherapy #proteinkinaseinhibitors #targetedcancertherapy #drugdiscovery #drugdevelopment #clinicaltrials #pharmacology #toxicology #pharmacogenomics #pharmacokinetics #tumordrugresistance #pharmacovigilance #pharmacoeconomics

Journal of Chemotherapy - Special Collection Invitation - Protein Kinase Inhibitors for Targeted Cancer Therapy - Reminder Dear Colleagues,    As a Guest Co-Editor, I renew my invitation to you to submit a review or research manuscript of yours to the special collection entitled “Protein Kinase Inhibitors for Targeted Cancer Therapy” in Journal of Chemotherapy.   While a wide range of different protein kinase inhibitors is available in clinical oncology practice and remarkable clinical success has been achieved with their use, limitations in the field remain and further discovery as well as in depth biological comprehension of their mechanisms of action and resistance is needed.   The editors of Journal of Chemotherapy aim to stimulate discussion on the discovery, development, and clinical applications of protein kinase inhibitors through a curated collection of high-quality reviews and original research articles.   Articles submitted to the collection will be assessed and peer reviewed per regular journal processes. More information on the scope of the collection can be found at this link:   http://bit.ly/3QrcZdl    or on the journal website (https://lnkd.in/dtPGeZkD).  Please note this is an Open Access collection. You may find information on benefits of OA publishing with JOC at: https://lnkd.in/dj2fwGDn   The deadline for manuscript submission has been set on 31 October 2024.   I hope you will consider publishing in this collection and contributing to build a higher impact journal together with other distinguished scientists from all the countries!   If you have any questions about the collection scope or the appropriateness of your contribution, please reach out.   Best regards,   Enrico Mini M.D., Ph.D. Guest Co-Editor Special Collection “Protein Kinase Inhibitors for Targeted Cancer Therapy” Journal of Chemotherapy #proteinkinaseinhibitors #targetedcancertherapy #drugdiscovery #drugdevelopment #clinicaltrials #pharmacology #toxicology #pharmacogenomics #pharmacokinetics #tumordrugresistance #pharmacovigilance #pharmacoeconomics

We are highlighting the cover story of Antibody Therapeutics (2023 CiteScore: 8.7), the official journal of Chinese Antibody Society published by Oxford University Press. The 12th cover story we would like to share is entitled “Preclinical evaluation of MRG002, a novel HER2-targeting antibody-drug conjugate with potent antitumor activity against HER2-positive solid tumors” contributed by Hui Li from Shanghai Miracogen. ERBB2 is a proto-oncogene of multiple cancers including breast and gastric cancers with HER2 protein overexpression or gene amplification and has been proven clinically as a valid target for these cancers. Here researchers reported the making of MRG002, a novel HER2-targeted antibody drug conjugate (ADC), and preclinical characterization including pharmacology, pharmacodynamics and toxicology and discuss its potential as a novel agent for treating patients with HER2-positive solid tumors. Featuring hyper-fucosylation of trastuzumab by design and clinically proven linker-payload, MRG002 exhibited reduced ADCC activity yet strong antitumor activity in trastuzumab- or T-DM1-resistant HER2-expressing PDX models. MRG002 has the potential to become one of the best HER2-targeting agents to address significant unmet medical needs in high- or medium-to-low HER2 expressing solid tumors. Click the link for the free access of the full text of the cover story: https://lnkd.in/d36GzsYc We are also welcoming therapeutic antibody related submission through https://lnkd.in/dMJjtiD #Antibody #Therapeutics #Coverstory

Testing firm Genialis has announced the commercial availability of its krasID test, which it calls: “the first biomarker algorithm that predicts patient response and clinical benefit to KRAS inhibitors (KRASi) across tissue histology and mutation type.”  Genialis’s krasID was developed to help guide drug development from early preclinical phases, to clinical trials (e.g., patient selection for clinical trials and identification of combination therapies), and to market access and clinical care, including providing the ability to maximize time on drug and inform combinations. “KRASi hold transformative potential for cancers like NSCLC, CRC, and PDAC, but for these drugs to achieve their full impact, we need better tools to understand who are the right patients,” said Mark Uhlik, PhD, vice president of biomarker development at Genialis. “Genialis krasID represents a significant leap forward in personalizing cancer care.” The new test uses machine learning (AI/ML) to model dozens of biological processes from the gene expression of patient-derived tumors, providing more information and predictive power than traditional mutation-based diagnostics. It has been validated on real-world data from G12C non-small cell lung cancer (NSCLC) patients and myriad other preclinical and PDX samples across colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), where it has shown pan-RAS, pan-tissue applicability. Traditional KRAS tests, the company points out, only detect the presence or absence of DNA mutation and they cannot inform time on treatment or combination strategies. Genialis krasID integrates signal from KRAS biology with surrounding tumor milieu using RNA-seq & ML. It predicts response with >94% accuracy in preclinical models and >80% accuracy in real world patients. It also stratifies patients based on time on treatment/survival. KRAS mutations contribute to approximately 1.6 million new cancer cases globally each year, predominantly in NSCLC, CRC, and PDAC. Current therapies primarily target only G12C mutations, which leaves as many as 50 percent of patients with cancer driven by a KRAS mutation without targeted treatment options.

Rgenta Therapeutics Inc. announced the FDA clearance of their IND application for RGT-61159, a groundbreaking oral small molecule RNA modulator. RGT-61159 is designed to inhibit the production of the disease-driving MYB protein, targeting adenoid cystic carcinoma (ACC) and colorectal cancer (CRC). The upcoming first-in-human Phase 1a/1b clinical trial will evaluate the efficacy of RGT-61159 in selectively targeting MYB RNA and preventing oncogenic MYB protein production. This trial is backed by promising preclinical data recently showcased at the ASCO 2024 Annual Meeting. Rgenta Therapeutics, a leader in the development of novel oral small molecules for oncology and neurological disorders, is pioneering new treatment avenues with RGT-61159. The clearance by the FDA marks a significant milestone in advancing potential therapies for ACC, CRC, other solid tumors, and acute myeloid leukemia (AML). This advancement underscores Rgenta's commitment to innovation in cancer treatment and is poised to impact the oncology therapeutics market by offering new hope to patients with limited options. The successful development of RGT-61159 could drive healthcare market growth, establishing Rgenta Therapeutics as a key player in the oncology therapeutics market. https://lnkd.in/gqQTSJUN #healthcare #oncology #oncologytherapeutics #Rgentatherapeutics #adenoidcysticcarcinoma #innovation #growth

Goebeler, ME., Stuhler, G. & Bargou, R. Bispecific and multispecific antibodies in oncology: opportunities and challenges. Nat Rev Clin Oncol (2024). https://lnkd.in/dRR4dn4S "Abstract Research into bispecific antibodies, which are designed to simultaneously bind two antigens or epitopes, has advanced enormously over the past two decades. Owing to advances in protein engineering technologies and considerable preclinical research efforts, bispecific antibodies are constantly being developed and optimized to improve their efficacy and to mitigate toxicity. To date, >200 of these agents, the majority of which are bispecific immune cell engagers, are in either preclinical or clinical evaluation. In this Review, we discuss the role of bispecific antibodies in patients with cancer, including history and development, as well as innovative targeting strategies, clinical applications, and adverse events. We also discuss novel alternative bispecific antibody constructs, such as those targeting two antigens expressed by tumour cells or cells located in the tumour microenvironment. Finally, we consider future research directions in this rapidly evolving field, including innovative antibody engineering strategies, which might enable more effective delivery, overcome resistance, and thus optimize clinical outcomes. Key points Following the approval of blinatumomab in 2014 for use in patients with relapsed and/or refractory B cell acute lymphoblastic leukaemia, a further ten bispecific antibodies have been approved by regulators globally and a further >200 bispecific antibodies, with increasingly diverse designs and mechanisms of action, are currently in preclinical or clinical development. Identifying the most appropriate target antigen is a major challenge for the successful development of bispecific antibodies, especially in solid tumours, and holds the key to creating safe and effective off-the-shelf agents for clinical application. Bispecific antibodies are able to recruit immune cells into the vicinity of tumours and enable them to thrive in the immunosuppressive tumour microenvironment owing to their ability to overcome the effects of various inhibitory factors and provide stimulatory signals capable of restoring antitumour activity. Bispecific antibodies targeting two or more pathways involved in tumour progression simultaneously might reduce the risks of drug resistance and tumour progression compared to monotherapy with agents targeting one of the same pathways. Strategies to mitigate cytokine release syndrome have been identified, such as pretreatment with steroids, step-up dosing, subcutaneous administration, modification of CD3ε affinities and prodrug concepts. The optimal clinical use, including treatment sequencing and the identification of possible combination therapies, remains uncertain for most of these agents."

Bispecific antibodies targeting two or more pathways involved in tumour progression simultaneously might reduce the risks of drug resistance and tumour progression compared to monotherapy with agents targeting one of the same pathways. Strategies to mitigate cytokine release syndrome have been identified, such as pretreatment with steroids, step-up dosing, subcutaneous administration, modification of CD3ε affinities and prodrug concepts. The optimal clinical use, including treatment sequencing and the identification of possible combination therapies, remains uncertain for most of these agents. #phase1 #bispecific #ADC #CD3

We are proud to announce our significant contribution to a seminal scientific paper focused on Antibody-Drug Conjugates (ADCs) in the clinical landscape. The paper delves, among other aspects, into an extensive analysis of the physicochemical properties of ADC payloads, yielding crucial insights pivotal for the strategic design and advancement of ADC therapies. As a leader in innovative biotechnological solutions, CancerAppy team played a high relevant role in the collaborative effort that culminated in this comprehensive examination. The paper’s findings promise to revolutionize the development and optimization of ADCs, offering a clearer understanding of the relationship between payload properties and therapeutic efficacy. ADCs represent a pivotal therapeutic advancement, effectively applied across diverse clinical scenarios. Comprising antibodies targeting tumor-associated antigens (TAAs), cytotoxic payloads, and binding linkers, ADCs have primarily focused research on target identification, antibody design, and linker optimization, leaving other critical clinical facets understudied. In this work, the researches performed a comprehensive assessment of approved ADCs and analyzed properties such as payload physicochemical attributes, potency, drug antibody ratio (DAR), exposure–response correlations, and development strategies. Optimal clinical candidates feature ideal payload properties and cleavable linkers, particularly impactful in low TAA expression contexts. Additionally, early clinical tactics, including altered dosing schedules, aim for enhanced efficiency. This analysis emphasizes overlooked facets essential for ADC cancer development, proposing avenues for refinement. Dr. Elisa Poyatos, Chief Scientific Officer at CancerAppy, expressed enthusiasm about the company’s involvement in this groundbreaking endeavor, stating, “Our team’s commitment to pushing the boundaries of scientific knowledge has motivated our dive into the intricate details of ADCs. By conducting thorough analysis and partnering with respected researchers, we’ve uncovered crucial understandings about the physicochemical characteristics of ADC payloads. This knowledge might empower the industry to create therapies that are more effective and impactful.” This collaborative scientific effort underscores CancerAppy’s commitment to pioneering advancements in biotechnology and reinforces its dedication to fostering innovation within the industry. The complete work has been published in the Journal of Hematology & Oncology, with an impact factor of 28.5 (2022); and can be read with open access at the following link: https://lnkd.in/dk9KTJ_B

Gilead removes anti-CD47 antibody from pipeline, $4.9 Bn write off of Forty Seven purchase. What is the status of other anti-CD47 programs? CD47 is a surface receptor that appears to function in modulating immune cell killing, hence "do not eat me" signal. Discovery of this biology and blockade in preclinical models with tumor killing led to a frenzy of biotechs targeting this receptor, perhaps the next Big Thing in oncology (this was before ADCs became the next Big Thing, again) A few months ago, Gileads magrolimab anti-CD47 mAb was put on hold due to patient deaths. Indeed, CD47 is found on many hematological cell types, a worrisome fact that risks side effects. Now Gilead has completely removed it from the pipeline, a huge loss for the company. What does this portend for the other CD47 oncology therapies, with so many in the clinic? Is the Gilead results a molecule specific effect, or a class effect? Alternate drug targeting strategies may hold the key. Clinical Trial Arena - " Despite these setbacks, interest in CD47 as a therapeutic target remains strong, with 43 CD47-targeting drugs in clinical development globally. ALX Oncology‘s evorpacept, I-Mab‘s lemzoparlimab, and Viego Therapeutics’s VT-1021 are the CD47 products that are currently in Phase III clinical trials. Lemzoparlimab is a monoclonal antibody such as magrolimab, while the other two Phase III agents employ distinct modes of action. Evorpacept is a fusion protein with a high-affinity CD47 binding domain of SIRPα linked to an inactive Fc region of human immunoglobulin. This strategy minimises toxicity by avoiding Fc receptor engagement on immune cells, thus concentrating therapeutic effects within the tumor microenvironment. Results of the Phase II/III ASPEN-06 clinical trial revealed that evorpacept’s addition to Roche’s trastuzumab, Eli Lilly’s ramucirumab, and paclitaxel had an overall response rate of 52%, compared to 22% in the control group, in HER2-positive gastric/gastroesophageal junction cancer. " ---- Disclaimer - Views expressed here are of the Author only. https://lnkd.in/eF-dDXxT