Isabel Perez-Cruz’s Post

Excited to announce the release of our latest article published in Clinical Pharmacology and Therapeutics titled "Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta-Analysis'. This analysis included data on CRS from 1,560 patients in 36 studies of BCMA-targeting CAR-Ts and bispecific antibodies (BsAbs). The analysis showed that BCMA CAR-T therapies exhibit higher CRS incidence, severity, longer CRS duration, and more prevalent tocilizumab usage compared to BsAbs. Further, SC administration of BsAbs was associated with lower incidence of CRS vs IV administration. Read the full article (available online): https://lnkd.in/g-cQP_a9 Thanks for all co-authors, specially Pooneh Soltantabar, PhD and Sheena Sharma, the two first authors who contributed equally to this work.

In 2023, GlobalData's Pharmaceutical Intelligence Centre reported the initiation of 22,338 #clinicaltrials . Oncology emerged as the primary focus, followed by the central nervous system. Among the trials commenced that year, the predominant phase was Phase II, constituting 36% of the total. Additionally, 7,183 clinical trials concluded in 2023, with 6,234 successfully completed and 777 terminated. Biggest success stories in 2023. Eli Lilly and Company donanemab has reported positive outcomes from its Phase III trial (NCT04437511) focused on Alzheimer's disease. Vertex Pharmaceuticals and CRISPR Therapeutics are collaborating on the gene therapy known as exagamglogene autotemcel (exa-cel). This therapy, to be marketed under the brand name #Casgevy, is intended for individuals with #sicklecelldisease and transfusion-dependent beta-thalassemia HEMEX Leading clinical trials with detail, efficiency, and excellence

🚀 𝙀𝙭𝙘𝙞𝙩𝙞𝙣𝙜 𝙍𝙚𝙜𝙪𝙡𝙖𝙩𝙤𝙧𝙮 𝘼𝙥𝙥𝙧𝙤𝙫𝙖𝙡𝙨 𝙞𝙣 𝘽𝙞𝙤𝙥𝙝𝙖𝙧𝙢𝙖 𝙛𝙤𝙧 𝙈𝙖𝙮 & 𝙅𝙪𝙣𝙚 2024!🧬 Despite the complexities, recent regulatory approvals highlight promising advancements in oligonucleotide and biological therapies across the EU and US. 🔬 𝗞𝗲𝘆 𝗔𝗽𝗽𝗿𝗼𝘃𝗮𝗹𝘀: 𝗢𝗻𝗰𝗼𝗹𝗼𝗴𝘆 𝗕𝗿𝗲𝗮𝗸𝘁𝗵𝗿𝗼𝘂𝗴𝗵𝘀: ◾ Novartis acquired Mariana Oncology for its radiopharma focus on actinium. ◾Biogen acquired Human Immunology Biosciences for its anti-CD38 monoclonal antibody. ◾Merck acquired Eyebiotech for $3B, focusing on ophthalmology. ◾KEYTRUDA (#pembrolizumab) approved for primary advanced or recurrent endometrial carcinoma, combined with chemotherapy. 𝗖𝘂𝘁𝘁𝗶𝗻𝗴-𝗘𝗱𝗴𝗲 𝗧𝗵𝗲𝗿𝗮𝗽𝗶𝗲𝘀: ◾QALSODY (#tofersen) by Biogen for ALS, targeting a genetic cause of the disease. ◾RYTELO™ (#imetelstat) by Geron Corporation for lower-risk myelodysplastic syndromes (#LR-#MDS), showing promising transfusion independence. 𝗠𝘂𝗹𝘁𝗶𝗽𝗹𝗲 𝗦𝗰𝗹𝗲𝗿𝗼𝘀𝗶𝘀: A new biologic therapy approved by the European Commission, providing a twice-yearly subcutaneous option for relapsing and primary progressive MS. 🧪 𝗖𝗼𝗻𝘁𝗶𝗻𝘂𝗲𝗱 𝗜𝗻𝗻𝗼𝘃𝗮𝘁𝗶𝗼𝗻: FRUZAQLA (#fruquintinib), is the FIRST new targeted therapy for metastatic colorectal cancer in the EU in over a decade. 🔗 Read more about recent advances in biopharma! 👇 #Biopharma #Innovation #RegulatoryApprovals #Healthcare #Therapeutics #MS #Oncology #ALS #RDM #Biotechnology 🔵

Immunotherapies for high grade.gliomas are currently in development and are mechanistically diverse, and each therapeutic approach involves complexities in preclinical and clinical study design that must be carefully considered for rigorous data to result. As more of these therapies are transitioned into clinical trials in pediatric and adult patients, a deep understanding of the expected local and systemic immunologic effects is essential to an appropriate trial design and incorporation of the appropriate bio-correlative studies. Successful clinical development of immunotherapies for HGG is likely to require a multi-institutional, consortia-based approach, with collaborations between academia and pharmaceutical companies. Here, the authors review in depth the TME in HGG, the various drivers of the anti-inflammatory TME in HGG, a current review of various immunotherapeutic approaches, and some of the recognized challenges to successful immunotherapy development. #highgradegliomatherapy #hggimmunotherapy

This week, BioInvent's Director Clinical Pharmacology Johan Wallin is in Rome at the Population Approach Group Europe #PAGE2024 annual meeting, presenting the model-informed early clinical development of our lead anti-TNFR2 antibody BI-1808. The poster describes how a model-informed approach can support and optimize clinical development. The aim was to characterize the population pharmacokinetics (PK), receptor occupancy (RO), and concentrations of the target engagement biomarker soluble tumor necrosis factor receptor 2 (sTNFR2) at different BI-1808 doses, to support the dose selection for the dose expansion trial. Data are confirming a wide potential dose-range of BI-1808 in the continued clinical evaluation which already has shown promising single agent safety and efficacy. BI-1808 could represent a new class of immunomodulatory agent with the potential to improve efficacy of cancer therapy. As earlier communicated, initial efficacy and safety data from the ongoing Phase 1/2a study show so far: - One complete response (CR), one partial response (PR) that is still improving, and nine patients with stable disease (SD) of 26 evaluable patients in the single agent arm of BI-1808 - Promising signs of efficacy and favorable safety profile in the Phase 1 dose escalation part studying BI-1808 in combination with KEYTRUDA® (pembrolizumab). “The data presented in this poster demonstrate our effective leveraging of a model-informed approach to support dose selection and optimization in the development of our immunomodulatory agent BI-1808," commented Martin Welschof, Chief Executive Officer of BioInvent. “The model confirms the wide potential dose range of BI-1808 and will be beneficial in the selection of doses as our clinical evaluation of the asset continues in the ongoing Phase 1/2a study, which has already produced promising initial safety and efficacy results." #immunooncology #immunotherapy #antibodytherapeutics #biotechnology #lifesciences

Avapritinib is the only potent and selective inhibitor approved for the treatment of D842V-mutant gastrointestinal stromal tumors (GIST), the most common primary mutation of the platelet-derived growth factor receptor α (PDGFRA). The approval was based on the NAVIGATOR trial, which revealed overall response rates of more than 90%. Despite this transformational activity, patients eventually progress, mostly due to acquired resistance mutations or following discontinuation due to neuro-cognitive side effects. These patients have no therapeutic alternative and face a dismal prognosis. Notable, little is known about this drug’s binding mode and its medicinal chemistry development, which is instrumental for the development of the next generation of drugs. Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration. #Avapritinib #PreClinical #DrugDiscovery #inhibitor #Medchem #CRO #FFS https://lnkd.in/gwmq2sGW

Biologics are complex medicines made by living cells that can, because of their larger and more complex molecular structure, provide precise and personalized treatments with potentially fewer side effects and safety concerns. Therapeutic antibodies are now being explored for their potential in treating infectious and neurodegenerative diseases, metabolic disorders, and cardiovascular conditions, showcasing their expanding role in modern medicine. Working across immunology and neuroscience, Teva is focused on identifying highly targeted antibodies to fight disease. With recent launches and an extensive pipeline, Teva has acquired industry-leading experience in screening and selecting disease-fighting antibodies for effective therapies. Discover more about Teva’s innovative work in this space: https://ow.ly/JOzl50TLw7F #InnovativeMedicines #Tevapharm #WeAreAllInForBetterHealth

GT-02287 (Gain Therapeutics), an orally administered, brain-penetrant small molecule, is designed to restore the function of the lysosomal enzyme glucocerebrosidase (GCase) in patients with GBA1 Parkinson disease (PD). According to the company, the agent was discovered via Gain’s Site-directed Enzyme Enhancement Therapy (SEE-Tx) drug discovery program. In preclinical models, investigators observed that the agent restored GCase enzymatic function, reduced aggregated α-synuclein, neuroinflammation and neuronal death, increased dopamine levels, and improved motor function. In October 2023, the company announced that dosing commenced for the phase 1 trial of GT-02287 in healthy individuals. The trial is a randomized, double-blind study that features both a single- (SAD) and multiple-ascending dose (MAD) component. Mainly intended to evaluate the safety and tolerability of GT-02287, the study includes several secondary objectives such as the pharmacokinetics of SAD and MAD dose levels to identify a maximum tolerated dose as well as identify recommended doses for further clinical development. The trial will also assess the agent’s impact on GCase, which becomes misfolded and dysfunctional because of the GBA1 gene mutation. Recently, Joanne Taylor, PhD, senior vice president of research at Gain Therapeutics, sat down in an interview with NeurologyLive® to share some of her scientific insights on the agent such as its mechanism of action and implications from preclinical data. She talked about how GT-02287 aims to address the cellular dysfunctions associated with PD by targeting the GCase. Beyond Parkinson, she spoke about the evidence that suggests GT-02287, might have applications in other neurodegenerative diseases such as Alzheimer disease. With GT-02287 in a phase 1 clinical trial, Taylor discussed some of the biomarkers that are being examined to assess its neuroprotective effects in healthy patients. REFERENCES 1. Gain Theraprutics announces dosing of first two subjects in phase 1 clinical trial of GT-02287, a novel CGase-targeting small molecule therapy for GBA1 Parkinson’s disease. News release. Gain Therapeutics. October 4, 2023. Accessed January 26, 2024. https://lnkd.in/ecXxNhfN

Longitude portfolio company Poseida Therapeutics, Inc. recently announced that the FDA has granted Orphan Drug Designation for the treatment of multiple myeloma to P-BCMA-ALLO1, a novel BCMA-targeted allogeneic, T stem cell memory (TSCM)-rich chimeric antigen receptor (CAR)-T therapy candidate. "The Orphan Drug Designation for P-BCMA-ALLO1 underscores the high unmet medical need for a rapid and accessible off-the-shelf allogeneic CAR-T therapy for patients with multiple myeloma," said Poseida President and CEO Kristin Yarema, Ph.D. "This designation further validates our belief that TSCM-rich allogeneic CAR-T therapies may potentially offer the optimal combination of clinical results, on-demand availability, and high-volume production, while supporting broader access to CAR-T therapies." Learn what's next for P-BCMA-ALLO1: https://lnkd.in/egymCpGK #celltherapy #genetherapy

Findings from this ASCPT survey- 92% of responses suggest that PD biomarkers are at least useful. Clinical Exposure-response modeling (57%) followed by pharmacokinetic (PK)/PD modeling (28%) are most preferred approaches for selecting doses. Dose optimization for antibody-drug conjugates was viewed to be moderately complex. The approved doses of 25 targeted therapies were examined and the average free concentration at steady state (Css) was determined to be similar to the in vitro cell potency (half-maximal inhibitory concentration (IC50) -the drug is an inhibitor of Porcupine, a membrane-bound O-acyltransferase required for Wnt secretion. Wnt pathway is expressed in skin tissues; AXIN2 mRNA expression in skin is a robust and sensitive biomarker for the Wnt pathway. A predominant safety issue in this case is dysgeusia. The authors performed integrated population PK and exposure-response analyses of PD biomarker and safety data to determine the recommended dose for expansion, rather than the conventional maximum tolerated approach.