Myriad Genetics’ Post

A new paper from Genentech authors describes the preclinical characterization and phase 1 trial results for DHES0815A, a HER2-directed antibody-drug conjugate that was terminated recently due to safety concerns. From the introduction: The data herein describe design of DHES0815A, mechanisms of action, efficacy in HER2+ and HER2-low xenograft models, safety studies in non-human primates, and phase 1 safety and efficacy data. In this work we show that, despite strong and compelling preclinical data and early signs of anti-tumor activity in patients, a number of persistent safety findings resulted in termination of the phase 1 study. #mabs https://lnkd.in/efZ8i6_v

Another great paper from Genentech, this time describing the preclinical development and Phase 1 trial of their PBD monoalkylator ADC. One of the best things about this paper is that they explain why the trial was discontinued. As the authors point out, this level of transparency is not common and should be encouraged whenever possible so that the ADC community can learn not only by sharing successes but also from sharing our challenges and roadblocks.    https://lnkd.in/eTt-_WqG

sharing this post about our recent paper and why we thought it was important to disclose lessons learned in ADC development (and not just the successes).

To evaluate the safety, tolerability and efficacy of therapeutic drug candidates, preclinical animal models are used to assess adverse side effects before a drug advances to clinical trials. Our use of syngeneic mouse tumor models enables us to assess the efficacy of immunotherapies due to the intact murine immune system. Don’t forget to check out our posters 125, 124, 123, 113, 116, 1531, 5339, LB363, LB365, 5345, 5346 to learn how our off-the-shelf mouse models are a promising preclinical resource, or set up a meeting at the booth 939 at AACR: https://lnkd.in/dTTkD7z3 #AACR2024 #AACRConference #AACRMeeting #CancerAwareness #TumorResearch #immunodeficient #preclinicalresearch #immunotherapy #cancerresearch #cancertherapy #PreclinicalStudies #HumanizedModels #renbiologics #antibodylibrary

One of Oncopeptides’ unique technology platforms presented – the SPiKE technology platform. Oncopeptides recently participated in the Swedish Pharmaceutical Society’s (Apotekarsocieteten) 4th Swedish Medicinal Chemistry Symposium, highlighting recent advances in Swedish drug discovery research in academia and in industry. This year, the meeting focus on novel concepts used in medicinal chemistry and chemical biology, including case stories. One of the novel concepts were presented by Oncopeptides’ Head of Research Stefan Svensson Gelius, who held a scientific presentation of one of our two technology platforms – the SPiKE (Small Polypeptide based innate Killer Engagers) platform. The title of the talk was “Affibody-based hBCMA x CD16 dual engagers for NK cell-mediated killing of multiple myeloma cells” and results supporting the concept were presented. This technology utilizes the immune system to fight cancer, as the SPiKEs are designed to bind to both NK-cells (Natural Killer cells) and specific targets on various cancer cells. The functionality of this proprietary platform is currently under preclinical validation for both solid tumors and hematologic malignancies, and the concept may have a potential to reduce side-effects, whilst achieving similar levels of clinical efficacy as current T-cell based treatments. Want to learn more about Oncopeptides technology platforms and pipeline? Please visit our website to read more, link in the comments below. #Hematology #Innovation #Research #MultipleMyeloma

A recent Yahoo News article mentioned that Gilead licensed Xilio’s XTX301, a tumor-activated IL-12, which served as another proof of concept (POC) for pro-drug application. Over the past decade, the foundational technology for antibody prodrugs and cytokine prodrugs has matured, with the crucial aspects lying in the details. MMP's cleavage efficiency in the TME is limited. Therefore, designing and obtaining a prodrug with appropriate pharmacokinetics (PK) and achieving an appropriate safety/efficacy balance after cleavage are crucial. The direction of prodrug technology application is also significant. Both cytokines and TCEs require corresponding low concentrations to be effective in the TME, making them suitable candidates for prodrug development. Janux’s recent encouraging data on JANX007 (PSMA/CD3) serves as a proof of concept for prodrug’s application on TCE. AI/CAAD technology could model a prodrug in silico and test different masking peptides in silico, not only for predicted safety/efficacy balance but also for predicted manufacturability of complex proteins. I believe Ab Studio’s “In silico design + in silico validation + bench validation” workflow will serve as a very unique and valuable platform for novel prodrug design and development. 😊 https://lnkd.in/gMd6WaYk

Jacob Plieth has provided an insightful review of MYTX-011. While many ADC developers focus on topo1 inhibitor payloads and bystander effects, MYTX-011 emphasizes enhancing intracellular payload delivery, addressing a fundamental issue in ADC pharmacology. The linker-payload is familiar to us, representing a back-to-basics approach yet standing somewhat apart from mainstream strategies, creating a curious situation. A few years ago, I came across a study by E. Sally Ward et al. (2019) exploring pH-dependent antibodies and ADCs targeting HER2 using a mechanism similar to MYTX-011. Additionally, although not directly related to ADC research, BioNTech SE's gotistobart (an anti-CTLA-4 mAb) also employs pH-dependent antibodies to induce target recycling, thus minimizing the autoimmune side effects associated with CTLA-4 depletion (Zhang Y et al., 2019). I am eager to review the clinical data for MYTX-011 that will be presented at upcoming medical congresses. Ref: https://lnkd.in/gCsqne9V https://lnkd.in/g7u_dREd https://lnkd.in/g6J5QKP9

Looking to build in vitro cardiotoxicity and cardiac disease models? Read about our work and download our new 2024 Cardiac Guide! Last week, we attended the Society of Toxicology 63rd Annual Meeting and ToxExpo, discussing our work using human iPSCs for cardiotoxicity and neurotoxicity screening. We received an incredible response to our cardiotoxicity offerings, including: • A new axoCells™ Atrial Kit product, offering an all-in-one bundle for in vitro atrial fibrillation modeling • Two exciting concepts that we're working on, with a view to enhancing the purity and maturity of iPSC-derived cardiotoxicity models • Our range of capabilities to support cardiac safety researchers including custom lab services, iPSCs and collaborative model building We've rounded up our cardiac and cardiotoxicity offerings into our 2024 Cardiac Guide, which you can download by clicking the link in the article below. https://hubs.ly/Q02pMZh80 If you'd like to discuss a project, get in contact at [email protected] #iPSCs #cardiotoxicity #CiPA #AtrialFibrillation #SOT2024

ANGLE PLC (AIM:AGL, OTCQX:ANPCY) said it has secured a European patent for its CellKeep slide, with US intellectual property protection from the US set to follow soon. This innovative device reduces cell loss by over 70% during the microscopy analysis of circulating tumour cells (CTCs), a common challenge in clinical oncology and pharmaceutical research. This attrition is particularly impactful as CTCs, critical for cancer diagnosis and research, are typically few in number in blood samples. ANGLE's solution not only minimises cell degradation but also protects their structural integrity, a factor crucial for accurate analysis and research outcomes. The technology integrates seamlessly with ANGLE’s liquid biopsy system, Parsortix, designed to efficiently capture intact and viable CTCs from blood samples. More at #Proactive #ProactiveInvestors #Angleplc #cellkeep http://ow.ly/k2Yy105qeHc

PARP1 selective inhibitor yields potent and durable antitumor activity in patient-derived preclinical models