Listen to a recording of the Nov 2019 Monthly Scientific Meeting
Listen to M4K Pharma’s Scientific Update Meeting from November 6th, 2019 where our scientists and collaborators discuss the latest progress in our Medicines4Kids project for a deadly children’s brain cancer called DIPG. Join us to hear first-hand how we are developing a medicine using an open science collaborative approach!
In today’s virtual meeting, Dr. Methvin Isaac from OICR opened with an overview of progress against CTIP grant milestones. The team is collectively working towards optimizing compounds from three chemical series, including five lead compounds that have met our target product profile, as inhibitors to the mutated ALK2 protein.
Our Structural Genomics Consortium (SGC) collaborators from Prof. Alex Bullocks’ lab at Oxford University shared an update on in vitro assays testing for potency and off target activity of backup compounds in DIPG cell lines. They also presented a 3D structure model to explain why two of the compounds bound poorly to the G356D- mutated ALK2 protein.
Dr. Ahmed Aman (OICR) shared results from formulation studies confirming that aqueous methylcellulose can be used as an alternative to the DMSO-containing vehicle currently used for in vivo studies. There was a typical slight reduction in exposure of the compound in the plasma relative to the DMSO formulation. The urgent need to change the vehicle is in response to results from recent DIPG efficacy studies in mice which suggested that the vehicle may be causing toxicity in the form of weight loss.
Dr. Angel M Carcaboso from Hospital Sant Joan de Déu Barcelona shared an update on the efficacy studies with M4K2009, one of our lead compounds, using a DIPG xenograft mouse model. The treated group lost less weight than the control group and survived 7-9 days longer. As the vehicle contains DMSO and seems to affect the health of the mice, interpreting the data is difficult. The experiment will need repeating with the new formulation using aqueous methylcellulose.
Dr. Sue Cramp from Charles River Laboratories (CRL) presented their progress to improve the physical and chemical properties of backup compounds from the Blueprint series. CRL chemists have been volunteering their time with M4K as part of their Corporate Social Responsibility program. Working with the AI company Atomwise, CRL is also identifying compounds related to M4K2009 that will have improved selectivity for ALK2 over ALK1 and ALK6, sister proteins to our target. The CRL team is also collaborating with SGC to develop brain penetrant and cell permeable PROTACs with newer analogues, to be used both as tools for knockdown and as potential drugs.
Everyone is invited to dial-in and join the live monthly meetings. To find out when our next meeting will be, follow us on twitter: @M4KPharma