On the Importance of Model Selection in Drug Testing For many human diseases, there are no true mouse equivalents. To still evaluate drug effectiveness in a complex, living organism, scientists have learned to engineer animal models that mimic selected aspects of human pathology. In essence, we take a mouse, deliberately disrupt one of its proteins, then “fix” it with a drug that restores what we just broke - and celebrate that we’ve cured the disease. Two major issues arise from this approach. First, such models often become benchmarks for drug testing despite capturing only a narrow mechanistic slice of the human condition. Treatments that look miraculous in mice frequently yield limited benefit in people. Second, these models are poorly suited for evaluating drugs that act through entirely different pathways and do not directly target the artificially overexpressed protein. In our recent bioRxiv preprint, ImmunoBrain tested an anti-PD-L1 blocking antibody in the PS19 mouse line - a tauopathy model that overexpresses mutated human tau (P301S). Unlike slower-progressing amyloid or tau models, PS19 mice develop rapidly advancing neurodegeneration with early mortality. Importantly, anti-PD-L1 does not target tau itself; it works by modulating immune activity in the periphery, which in turn supports natural repair processes within the CNS, regardless of the primary disease etiology. In previous studies using slower progressing mouse models of tauopathy, PD-L1 blockade was shown to ameliorate cognitive decline alongside sustained reductions in in pathological tau species. In contrast, in the aggressive PS19 model, while we observed a significant beneficial effect on cognitive performance, the effects on pathological tau were short-lived. This outcome aligns with the notion that a treatment that does not directly counteract the main driver of the model - in this case, massive tau overexpression – may be at a relative disadvantage in maintaining a long-lasting effect following a single dose. Our findings underscore how model kinetics can influence therapeutic outcomes and highlight the importance of calibrating treatment regimens accordingly. In humans, disease evolves over years rather than weeks, and this temporal difference is routinely considered during clinical translation. A similar awareness should guide comparisons between preclinical models. Careful interpretation is therefore essential - across models, not all “positive” or “negative” results are created equal. https://lnkd.in/dRgAYveA #Innovation #Biotech #HealthcareInnovation #TranslationalResearch #Neurodegeneration #DrugDiscovery #Neuroimmunology
Model selection in drug testing: A cautionary tale from tauopathy research
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🔬 Our latest study analyses the therapeutic effects of our PD-L1 blocking approach in the PS19 mouse model; a rapidly advancing model of tauopathy. Here, we report that a single injection of our treatment significantly improved cognitive performance in the mice, which was detectable 1-month post-treatment, along with a transient decrease in phosphorylated and total tau in the brain and cerebrospinal fluid, respectively, 14 days post-treatment. These findings are in-line with our own and others' previous findings demonstrating therapeutic effects of anti-PD-1/PD-L1 antibodies in mouse models of Alzheimer’s disease and tauopathies. ✅ ImmunoBrain is currently testing this approach in the clinic with the investigational drug IBC-Ab002, a fully human anti-PD-L1 antibody engineered for treating neurodegeneration in Alzheimer’s disease.
On the Importance of Model Selection in Drug Testing For many human diseases, there are no true mouse equivalents. To still evaluate drug effectiveness in a complex, living organism, scientists have learned to engineer animal models that mimic selected aspects of human pathology. In essence, we take a mouse, deliberately disrupt one of its proteins, then “fix” it with a drug that restores what we just broke - and celebrate that we’ve cured the disease. Two major issues arise from this approach. First, such models often become benchmarks for drug testing despite capturing only a narrow mechanistic slice of the human condition. Treatments that look miraculous in mice frequently yield limited benefit in people. Second, these models are poorly suited for evaluating drugs that act through entirely different pathways and do not directly target the artificially overexpressed protein. In our recent bioRxiv preprint, ImmunoBrain tested an anti-PD-L1 blocking antibody in the PS19 mouse line - a tauopathy model that overexpresses mutated human tau (P301S). Unlike slower-progressing amyloid or tau models, PS19 mice develop rapidly advancing neurodegeneration with early mortality. Importantly, anti-PD-L1 does not target tau itself; it works by modulating immune activity in the periphery, which in turn supports natural repair processes within the CNS, regardless of the primary disease etiology. In previous studies using slower progressing mouse models of tauopathy, PD-L1 blockade was shown to ameliorate cognitive decline alongside sustained reductions in in pathological tau species. In contrast, in the aggressive PS19 model, while we observed a significant beneficial effect on cognitive performance, the effects on pathological tau were short-lived. This outcome aligns with the notion that a treatment that does not directly counteract the main driver of the model - in this case, massive tau overexpression – may be at a relative disadvantage in maintaining a long-lasting effect following a single dose. Our findings underscore how model kinetics can influence therapeutic outcomes and highlight the importance of calibrating treatment regimens accordingly. In humans, disease evolves over years rather than weeks, and this temporal difference is routinely considered during clinical translation. A similar awareness should guide comparisons between preclinical models. Careful interpretation is therefore essential - across models, not all “positive” or “negative” results are created equal. https://lnkd.in/dRgAYveA #Innovation #Biotech #HealthcareInnovation #TranslationalResearch #Neurodegeneration #DrugDiscovery #Neuroimmunology
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An oral Alzheimer’s drug that crosses the blood–brain barrier without infusion or ARIA surveillance—could this be the long-awaited small-molecule alternative to antibody therapy? Galimedix Therapeutics, Inc. has completed a Phase 1 study of GAL-101 in more than 100 healthy volunteers, showing strong tolerability and central exposure. The program is now advancing toward Phase 2 in Alzheimer’s, aiming to block misfolded amyloid beta monomers before they form toxic oligomers. If successful, an oral therapy could reduce infrastructure demands, ease site operations, and lower patient burden compared to infusion-based protocols. The company is also running a parallel Phase 2 in dry AMD, offering potential cross-validation in neurodegeneration. The opportunity is clear, but so is the challenge: BBB penetration is not a guarantee of efficacy, and small molecules against Aβ have a mixed track record. Human target engagement markers and early cognitive signals will be the real test. Do you believe an oral small molecule can finally break through where so many Alzheimer’s approaches have failed—or will efficacy hurdles remain insurmountable? 𝐑𝐞𝐚𝐝 𝐌𝐨𝐫𝐞: https://lnkd.in/gbcEmGip #AlzheimersDisease #Neurodegeneration #ClinicalTrials #Biotech Alexander Gebauer Miriam Selka
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𝐓𝐡𝐞 𝐔𝐥𝐭𝐢𝐦𝐚𝐭𝐞 𝐆𝐮𝐢𝐝𝐞 𝐓𝐨 𝐎𝐧𝐜𝐨𝐥𝐨𝐠𝐲 𝐃𝐫𝐮𝐠𝐬 𝐈𝐧𝐝𝐮𝐬𝐭𝐫𝐲 (𝐋𝐚𝐭𝐞𝐬𝐭 𝐈𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧) | IndustryARC™ The Oncology Drugs Market was valued at 289.37 USD Billion in 2025 and is projected to grow to 763.21 USD Billion by 2035, reflecting a CAGR of 14.20% from 2025 to 2035. 𝐃𝐨𝐰𝐧𝐥𝐨𝐚𝐝 𝐒𝐚𝐦𝐩𝐥𝐞 𝐏𝐃𝐅 @ https://lnkd.in/gxMyW8dj 🔹𝐊𝐞𝐲 𝐀𝐩𝐩𝐥𝐢𝐜𝐚𝐭𝐢𝐨𝐧𝐬 : ➼ Treatment of solid #tumors (lung, breast, colorectal, etc.) — targeted agents and #immunotherapies are widely used as first-line and later-line options for common solid #cancers. ➼ #Hematologic malignancies (leukemia, lymphoma, multiple #myeloma) — CAR-T, targeted small molecules and #antibodytherapies are transformative here, with many approved and late-stage products. ➼ #Adjuvant / neoadjuvant therapy (pre- and post-surgery) — targeted and immune agents are increasingly used to #shrinktumors before surgery or reduce recurrence risk after #surgery. ➼ #Biomarker-guided precision therapy / companion #diagnostics — selecting patients by #genetic/molecular markers (EGFR, HER2, PD-L1, etc.) to maximize efficacy and minimize toxicity. ➼ Supportive / palliative #oncology and #treatment optimization — supportive #drugs (to manage side effects), novel dosing routes and therapy sequencing to improve quality of life and clinic efficiency. 📊 𝐆𝐞𝐭 𝐭𝐡𝐞 𝐅𝐮𝐥𝐥 𝐑𝐞𝐩𝐨𝐫𝐭 @ https://lnkd.in/gjee-Kdc ✔️𝐈𝐦𝐦𝐮𝐧𝐨𝐭𝐡𝐞𝐫𝐚𝐩𝐲 𝐚𝐧𝐝 𝐧𝐞𝐱𝐭-𝐠𝐞𝐧 𝐜𝐞𝐥𝐥 𝐭𝐡𝐞𝐫𝐚𝐩𝐢𝐞𝐬 𝐚𝐫𝐞 𝐚𝐜𝐜𝐞𝐥𝐞𝐫𝐚𝐭𝐢𝐧𝐠 : checkpoint inhibitors, CAR-T and T-cell platforms (and next-gen off-the-shelf approaches) are driving strong R&D investment, approvals and high CAGR within the oncology segment. ✔️𝐏𝐫𝐞𝐜𝐢𝐬𝐢𝐨𝐧 / 𝐭𝐚𝐫𝐠𝐞𝐭𝐞𝐝 𝐭𝐡𝐞𝐫𝐚𝐩𝐢𝐞𝐬 + 𝐜𝐨𝐦𝐩𝐚𝐧𝐢𝐨𝐧 𝐝𝐢𝐚𝐠𝐧𝐨𝐬𝐭𝐢𝐜𝐬 𝐚𝐫𝐞 𝐛𝐞𝐜𝐨𝐦𝐢𝐧𝐠 𝐬𝐭𝐚𝐧𝐝𝐚𝐫𝐝 : biomarker-driven targeted drugs (small molecules, #ADCs, #bispecifics) and diagnostics are shifting treatment paradigms from one-size-fits-all to personalized regimens, boosting uptake and premium pricing for novel agents. ✔️𝐂𝐨𝐦𝐦𝐞𝐫𝐜𝐢𝐚𝐥 & 𝐝𝐞𝐥𝐢𝐯𝐞𝐫𝐲 𝐢𝐧𝐧𝐨𝐯𝐚𝐭𝐢𝐨𝐧𝐬 : formulation, patents and market reshaping large biologics face biosimilar pressure and patent cliffs, while drug makers counter with new formulations combination regimens, and M&A to protect market. 𝐁𝐮𝐲 𝐍𝐨𝐰 𝐋𝐢𝐧𝐤 @ https://lnkd.in/gZ4FnaNb 𝐓𝐨𝐩 𝐋𝐞𝐚𝐝𝐢𝐧𝐠 𝐊𝐞𝐲 𝐏𝐥𝐚𝐲𝐞𝐫𝐬 𝐚𝐫𝐞: Takeda Oncology | Astellas Pharma China, Inc. | Daiichi Sankyo | ONO PHARMACEUTICAL CO., LTD. | Eisai Co., Ltd. | Chugai Pharmaceutical Co., Ltd. | Kyowa Kirin International plc. | Sumitomo Pharma Co., Ltd. | BeiGene | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | Hengrui Pharma | Innovent Biologics | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | HUTCHMED | Meditech | Otsuka Pharmaceutical Co., Ltd.
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A bunch of good news for you this friday: Rapport Therapeutics’ experimental drug RAP-219 cut seizures by an average of 77.8% in a Phase 2a trial, with nearly one in four patients experiencing no seizures during the two month treatment. The results are encouraging for people whose seizures persist despite multiple medications. The company plans to meet with the FDA before starting two Phase 3 trials next year. To improve adherence, Rapport is also developing a long acting injectable version. Retro Biosciences is preparing a clinical trial for a pill that aims to reverse Alzheimer’s disease. The treatment could restore cognitive function and reshape how longevity medicine is understood. Built on cellular reprogramming techniques, the trial will be the first test of its effects in humans. Researchers have designed an ultrasound helmet capable of modulating deep brain circuits without surgery. The device delivers unmatched precision while remaining safe, reversible, and repeatable. It could both advance brain research and offer new therapies for neurological conditions such as Parkinson’s disease, where deep brain activity is most affected. Between 1985 and 2023, global maternal mortality dropped by 57%, equivalent to roughly 365,000 fewer deaths per year. After 25 years of work, scientists in São Paulo have created a laminin based therapy that may reverse spinal cord injuries. In animal studies, the treatment reactivated dormant nerve pathways, restoring both movement and sensation after paralysis. Early human trials are planned, raising hopes for millions living with spinal cord damage. Israeli scientists have engineered enzymes that strip sugars from red blood cells, effectively turning all donated blood into universal type O. In lab studies, enzyme treated cells were compatible with every blood type, pointing to a potential solution for shortages and faster transfusions in emergencies.
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Research Scholar At. NIPER-AHMEDABAD, Pharmacology and Toxicology Department. ll NIPER 2024 ll GPAT 2024 ll CUET-2024 ll GPAT 2023 ll || BPHARM (GNCP) ll DPHARM (MCOP)
Groundbreaking Brazilian Drug, Considered Capable of Reversing Spinal Cord Injury, Presented in São Paulo university,Brazil. But the real question is: is this a breakthrough fact, or hype? Brazilian researcher Tatiana Coelho de Sampaio, PhD, professor at the Federal University of Rio de Janeiro,Presented in São Paulo. this therapy marks an extraordinary step forward in restoring movement for people living with paraplegia or quadriplegia. What is polylaminin? Polylaminin is a polymeric form of laminin, a protein naturally found in the extracellular matrix that supports nerve growth. By enhancing and stabilizing laminin’s regenerative power, Brazilian scientists believe polylaminin can trigger nerve fiber regrowth and reduce inflammation in damaged spinal cords. The drug is injected directly into the spinal cord after an injury. Once there, it appears to create an environment where neurons can reconnect and restore lost communication between the brain and body. The Human Trial That Shocked Researchers:- In early 2024, a small pilot clinical trial was launched in Brazil and published as a preprint on medRxiv. • Eight patients with severe spinal cord injuries received a one-time injection of polylaminin. • All were treated within days of their injury, when chances of natural recovery are extremely low. • Tragically, two patients did not survive due to the severity of their trauma. • The remaining six, however, experienced something unprecedented: each regained voluntary motor control below their injury site. For comparison, in past trials of other therapies, patients with complete spinal cord ruptures rarely show meaningful recovery. Still, this was a tiny, uncontrolled study – and much more evidence is needed. Evidence From Animals and Veterinary Studies:- • Rodent studies showed significant regrowth of axons and improved motor function after spinal cord injury. • In dogs with chronic paralysis, treatment with polylaminin led to measurable gait improvements over months, with no major side effects. What’s Next for Polylaminin? For polylaminin to become a real treatment available to patients, researchers must complete several crucial steps: • Peer-reviewed publication of full trial results. • Larger, randomized, multicenter clinical trials to confirm effectiveness. • Long-term monitoring to assess durability and safety. • Regulatory review and approval global authorities. • Scaled-up production that meets international medical standards. • Until then, it remains a hopeful experimental therapy – not yet a cure. Bottom line : is it real? The truth lies between miracle and media hype. Polylaminin has shown unprecedented early results, but the science is still it's infancy. For now, it represented extraordinary hope - notta proven cure. Reference:- 1) PubMed study on polylaminin in rats. 2)Frontiers in Veterinary Science 2025 3)https://lnkd.in/g3KqymFX. #SpinalCordInjury #polylaminin #AcutePhase
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Drug development with 3D #organoid–immune co-cultures🔬 At Doppl SA, we are bridging the gap between preclinical models and human biology. Our 3D organoid–immune cell co-culture platform enables evaluation of the safety and toxicity of cellular therapies and antibody-based drugs in a human-relevant context. Organoid co-cultures can be performed with human PBMCs or selected immune cell subsets — including T cells, neutrophils, NK cells, and more — to assess cytotoxicity, cytokine release, and tissue-specific immune responses. This approach helps to identify off-target effects and immune-mediated tissue damage before entering clinical trials, reducing risk and accelerating development. Want to learn more? 📖 Recommended reading: Nature Biomedical Engineering (2023) – “Analysis of off-tumour toxicities of T-cell-engaging bispecific antibodies via donor-matched intestinal organoids and tumouroids” 👉 Read here: https://lnkd.in/dv76qUyF Also explore our latest work: 📖 Cancers (2025) – “In Vitro Evaluation of the Safety and Efficacy of Cibisatamab Using Adult Stem Cell-Derived Organoids and Colorectal Cancer Spheroids” 👉 Read here: https://lnkd.in/eg_arMM8 📩 To learn more about our 3D platform or potential collaborations, reach out at info@doppl.ch #DopplSA #organoids #3DCellCulture #ImmuneCells #DrugDiscovery
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# non-internalising ADC In the last 14 days, #USPTO published a patent application (US20250281632A1) on non-internalising antibody–drug conjugates (#ADC) targeting the tumour-associated protein #LGALS3BP (also known as 90K or Mac-2 binding protein). Unlike conventional ADCs that require internalisation for activity, these constructs deliver cytotoxic agents extracellularly upon binding LGALS3BP in the tumour stroma or on the surface of tumour cells. 💡A newer strategy of ADC development bypasses the need for internalisation by targeting extracellular stromal antigens or matrix-associated proteins. Examples include antibodies against fibronectin extra domain A and tenascin C. These ADCs act locally at the tumour site, releasing cytotoxic drugs into the microenvironment, thereby killing both tumour cells and stromal components that support tumour progression. 💡 LGALS3BP is a large, oligomeric, heavily glycosylated secreted glycoprotein (~90 kDa subunits). It mediates cell–cell and cell–matrix adhesion and promotes angiogenesis independently of #VEGF. It interacts with galectins, integrins, tetraspanins, collagens, fibronectin, and #CD33-related #Siglecs, most of which enhance tumour progression and #metastasis. Elevated LGALS3BP levels are observed in multiple cancers, including breast, lung, pancreatic, #neuroblastoma, #melanoma, #mesothelioma, and #lymphoma. Clinically, high serum or tumour LGALS3BP correlates with poor prognosis, metastasis, and reduced response to chemotherapy. 💡This invention introduces a novel class of non-internalising ADCs targeting LGALS3BP, a glycoprotein abundantly expressed and secreted in multiple malignancies. By harnessing extracellular cytotoxic delivery, these ADCs overcome long-standing challenges of internalisation dependence and limited antigen density. ✅ Payload is released extracellularly upon antigen binding, bypassing internalisation requirements. ✅ Localised drug release exerts cytotoxicity against tumour cells and stromal elements critical for tumour growth and angiogenesis. ✅ Exploits abundant stromal LGALS3BP to amplify therapeutic effect. The inventors of this patent are Capone Emily , Giansanti Francesco , Ippoliti Rodolfo , Gentile Roberta , Stefano Iacobelli , Piccolo Enza , Sara Ponziani, Sala Gianluca from MediaPharma s.r.l. We look forward to further promising clinical data from this innovation. #antibody #cancer #oncology #DrugDevelopment #patent #intellectualproperty
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Today I learned why it’s harder to deliver drugs to kidneys. It comes down to the kidney’s complex architecture. Its filters, micro-circulation, and multiple compartments makes it tough for therapeutics to reach the right targets. [1] In fact, people who develop drugs for other organs and diseases have to think about how the kidneys will process those drugs in order to reach their targets safely and effectively. (See, the kidneys are super cool and important.) That’s where nanomedicine comes in. These are small ("nano") materials ranging from 1 to 1000 nanometers (nm). How small is that you ask? I had to look it up, but many nanomedicines fall in the 50–200 nm range (that's small enough to slip through many biologic barriers, but large enough to carry powerful drug payloads). [2] For reference, if a marble were one nanometer wide, then one meter would be the size of the Earth. That’s the scale scientists work on when designing nanomedicines. By packaging drugs in these nanoscale carriers, scientists can get treatments precisely where they’re needed, like the kidneys. It's already worked in other areas. Many therapeutic nanomedicines have been designed to treat various conditions, with a major focus on cancer treatments. Since the 1995 FDA approval of Doxil, ~100 nano-based formulations have gained approval! It’s early, but the field is growing fast—with dozens of new studies published just this year. Promising science, challenging translation. The image below is from the recent article published in Clinical Kidney Journal by Zoe Schoales, Pratyusha Ghosh, Anastasiia Vasylaki, Edgar Jaimes, and Ryan Williams. The figure shows a roadmap for clinical translation for kidney-targeting nanomedicines and ways to address potential roadblocks along the way. The authors write: "We are confident that a streamlined, team-based, patient-focused approach to clinical development of kidney-targeted nanomedicines will increase the likelihood of success and ultimately facilitate more rapid translation to the clinic." Great work team, excited to keep following along! Hey Owen Richfield, PhD, I'd love to explore this one in more depth if you're interested in talking math models and kidneys?.... -- Sources: [1] https://lnkd.in/evcnDr-n [2] https://lnkd.in/eYv7F-bW [3] https://lnkd.in/esmJ_3Vj *This work was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health
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