Lumosa Therapeutics Co., Ltd.’s Post

⁤EV Engineering for Targeted Cancer Therapy: Enhancing Efficacy and Precision. The review article by Ren et al. from Frontiers in Bioengineering and Biotechnology, present opportunities for innovation in drug delivery systems, highlighting several advancements and methodologies pertinent to EV production, modification, purification, and drug loading that could drive strategic development in therapeutic applications. Article link: https://lnkd.in/gYdnsAc8 #ExtracellularVesicles #DrugDevelopment #Oncology #Pharmaceuticals

The 2024 Nobel Prize in chemistry was awarded to David Baker for computational protein design and to Demis Hassabis and John Jumper for protein structure prediction. https://lnkd.in/g9b4xwcY

Chimeric Antigen Receptor (CAR) T cell therapy represents a major breakthrough in cancer treatment using immunotherapeutical approach. While ex vivo CAR T cell therapies have shown promise, they face significant challenges in manufacturing processes and costs. To address these issues, in vivo CAR T strategies have been developed, involving the direct infusion of CAR genes via engineered nanocarriers or viral vectors to generate CAR T cells in situ. The review article by Bui et al. discuss the key components, the gene editing tools of CAR T therapy, and the limitations of current ex vivo CAR T therapies, the in vivo strategies, as well as the challenges for in vivo CAR T therapy development. Article link: https://lnkd.in/gzraZYmD #Cancer #GeneDelivery #GeneTherapy #DrugDevelopment

The past year has witnessed a flurry of billion-dollar handshakes, underscoring the pharmaceutical industry's unwavering commitment to conquering cancer. While the volume of oncology deals may have peaked in the halcyon days of 2020-2021, the value of these agreements has soared to unprecedented levels. The therapy area has commanded over $200 billion in headline value over recent years, with 2022 alone accounting for a staggering $100 billion. As we navigate through 2024, the market maintains a robust pace, though it's unlikely to eclipse the dizzying heights of previous years. Interestingly, the pecking order of therapeutic focus areas has seen a reshuffling. Neurologic disorders, once the perennial runner-up, have been displaced by infectious diseases since 2020 – a seismic shift catalyzed by the global scramble to combat COVID-19. The period from July 2023 to July 2024 has been particularly noteworthy, with all top ten oncology deals crossing the billion-dollar threshold. The top deal is the colossal $22 billion agreement between Daiichi Sankyo and Merck & Co., focusing on antibody-drug conjugates (ADCs) for solid tumors. This deal structure, with its $4 billion upfront payment and innovative cost-sharing model, exemplifies the high-stakes nature of current oncology collaborations. Not far behind, Bristol Myers Squibb's partnership with SystImmune for a bispecific ADC targeting lung and breast cancer, valued at up to $7.9 billion, further illustrates the industry's willingness to bet big on promising technologies. The article noted that: 1. Nearly half of the top deals centered on antibodies or antibody conjugates, signaling a strong belief in this modality's potential. 2. Industry giants like Merck, Novartis, and Roche are flexing their financial muscles, each inking deals worth over $2 billion. 3. A striking 70% of these top-tier deals were at the platform or discovery stage, indicating a strategic shift towards securing assets earlier in the development pipeline. 4. Despite economic headwinds, the biopharma industry's resolve to innovate in oncology remains unshaken. As we look to the horizon, it's clear that in this high-stakes game, the winners will be those who can navigate the complex interplay of scientific innovation, financial acumen, and strategic foresight. Article link: https://lnkd.in/gHts8fih #Biotech #AntibodyDrugConjugate #Oncology #DrugDevelopment

Welcome to the era of AI-designed antibodies and small molecules. The article, "Generative AI platforms drive drug discovery dealmaking," from Biopharma Dealmakers discusses how generative AI is reshaping the landscape of drug discovery. as AI platforms like those of Xaira Therapeutics and Generate show that biomedicines are harnessing the power of diffusion models to craft biologic drugs with unprecedented precision. With Xaira securing a staggering $1 billion in initial funding, it's clear that investors are betting big on this AI-driven future. Pharmaceutical giants are also diving headfirst into the AI pool. AstraZeneca, AbbVie, and Sanofi are just a few of the big pharma companies making deals with AI-focused companies like Absci, BigHat Biosciences, and BioMap that worth hundreds of millions, if not billions of dollars. Can these AI-designed molecules like Insilico Medicine's INS018_055 progress through clinical trials, only time will tell. But one thing is certain, the future of drug discovery is being rewritten, one algorithm at a time. For drug development companies, the message is clear: embrace the AI revolution or risk being left behind in a rapidly evolving landscape where the next blockbuster drug might be born in silicon before it ever sees a lab. Article link: https://lnkd.in/ehS8M_5d #AI #ArtificialIntelligence #DrugDevelopment

The article "Protein isoform-centric therapeutics: expanding targets and increasing specificity" isn't just another scientific paper - it's a wake-up call for the pharmaceutical industry. Hansen et al. challenge the traditional "one gene, one protein" paradigm, to explore into other therapeutic possibilities. According to the article, approximately 90-95% of human protein-coding genes undergo alternative splicing. This biological complexity represents an unprecedented opportunity to develop highly specific and potentially more effective therapies. For drug development companies like Lumosa, this approach opens up exciting new pathways. The ability to target specific protein isoforms could be a game-changer in treating complex disorders where pan-inhibition of all isoforms might be toxic or poorly tolerated. The article outlines three distinct modes of action for protein isoform-centric drugs: isoform switching, isoform introduction or depletion, and modulation of isoform activity. Each of these approaches offers unique opportunities for drug development: -Isoform Switching: The potential to correct aberrant splicing patterns in diseases like neuronal ceroid lipofuscinosis 7 showcases the power of personalized medicine. -Isoform Introduction or Depletion: This approach could be particularly valuable in oncology, where specific cancer-associated isoforms could be selectively targeted or depleted without affecting healthy tissues. -Modulation of Isoform Activity: By targeting isoform-specific functions, we could develop drugs with improved safety profiles and reduced off-target effects. Further, the use of protein isoforms as targets for cell type-specific drug delivery and immunotherapy is a concept that aligns perfectly with the growing trend towards precision medicine. For drug developers, this could mean developing more targeted therapies for brain tumors or neurodegenerative diseases, potentially improving efficacy while reducing side effects. The article also highlights the potential of protein isoforms as diagnostic biomarkers and sources of cancer neoantigens. This opens up possibilities not just for therapeutic development, but also for companion diagnostics and personalized treatment strategies. However, as with any emerging field, challenges remain. The detection and functional characterization of protein isoforms are areas that require further research and technological development. Therefore, investing in these areas could provide a significant competitive advantage in the long run. The authors present a compelling case for shifting our focus in drug discovery towards protein isoforms. For pharma companies, embracing this approach could lead to the development of more specific, effective, and safer therapies. The question now is how quickly and effectively we can do so. Article link: https://lnkd.in/gWR47wtE #ProteinIsomers #PrecisionMedicine #DrugDiscovery #BiotechInnovation

The PDGF/PDGFR signaling pathway has become a critical focus in drug development due to its role in cellular growth and disease. "Current status of drugs targeting PDGF/PDGFR" by Ai et al. examines drugs that targets PDGF/PDGFR have shown their importance in various conditions like cancer, fibrosis, cardiovascular diseases, and neurodegenerative disorders. The pathway plays a role in key signal chains such as PI3K/AKT, Ras/MAPK, and JAK/STAT, suggesting potential for combination therapies and novel drug designs. New strategies, including drugs that hit multiple targets and PDGFR, may lead to groundbreaking treatments. Article link: https://lnkd.in/gMq4cfHu #DrugDevelopment #Biotech #GrowthFactor

The Mid-Autumn Festival, or Moon Festival, will fall on September 17, 2024. This is the day for the families to gather together and enjoy good food (BBQ time!). Lumosa will take a day off on this day, we will return to office on Wednesday September 18. #MidAutumnFestival #Mooncakes

Ankit Kankar examines recent clinical trial failures from major pharmaceuticals such as GlaxoSmithKline, Eli Lilly, AbbVie, and Novartis to give readers insights that may reshape the industry's future from these setbacks. The author reviewed trials covering health issues from asthma to depression, rheumatoid arthritis to heart failure. Each discontinued trial represents not just millions lost, but also delays in introducing breakthrough treatments to patients. This makes it vital for drug developers to review these failures and adjust development strategy accordingly.  -GSK's asthma drug GSK1234567 due to lack of efficacy shows the challenge of translating promising preclinical data into human outcomes, indicating the urgent need for more predictive preclinical models and biomarkers.  -Eli Lilly's LY9876543 for depression faced the dual challenge of insufficient efficacy and unexpected side effects. The scenario highlights the complexities of CNS drug development and the critical importance of patient stratification.  -AbbVie's ABV1234 for rheumatoid arthritis failed to outperform placebo, showing the need for truly differentiated assets and could drive interest in novel mechanisms of action or combination approaches.  -Novartis' heart failure drug NOV5678 failed on both efficacy and safety outcomes. The results underline the delicate balance required in cardiovascular medicine. These failures, while costly, are important lessons for drug developers to consider in drug development to drive innovation forward and push new ideas in trial design, data analytics, and regulatory strategies. The author also provides recommendations to take into account in drug development. For example, adaptive trial designs could find broader application across therapeutic areas, and the integration of real-world evidence and AI-driven predictive models could enhance our ability to identify promising candidates earlier and design more robust trials. These events underscore the value of diversified pipelines and risk-balanced portfolios. While 2024 has dealt some hard blows to the life sciences industry, it has also set the stage for a new era of innovation. We can overcome the challenges by embracing these lessons, adjust our approaches accordingly and bring innovative therapeutics forward. Article link: https://lnkd.in/gJF_YZ4H #ClinicalTrials #DrugDevelopment #PharmaceuticalIndustry

A recent study by Chen et al. shows a worrying pattern in FDA orphan drug approvals from 2017-2023. The researchers analyzed 87 pivotal efficacy trials for 72 new therapeutic agents. They found that about half (49.4%) were randomized, and a large number (48.7%) had support from ongoing randomized controlled trials. The FDA's method for orphan drug approvals shows a mix of strict clinical proof and flexible rules, with 44.7% of approvals based on one well-controlled trial plus backing evidence. Also, 72.4% of approvals had support from surrogate endpoints, which highlights how important new trial designs are to speed up drug development. The results emphasize why the drug development companies may consider investments into orphan drug development. The FDA's approval process, which is both flexible and strong, helps to facilitate faster drug approvals and increase chances of success for new treatments. Article link: https://lnkd.in/gnRqTfdR #OrphanDrugs #ClinicalTrials #PharmaBD #RareDiseases