I'm going to leave the bonus options and CEO appointment to one side and dump my thoughts on the updated strategy here, and may span over multiple posts . Apologies to all on this forum as this will be a long read, and apologies to my boss who has seen a significant drop in my productivity today.
RAC Updated StrategyComparison
Key Points
·Validation of the cardio protective effects of bisantrene (RC220) is now the primaryclinical focus of RAC’s clinical development program
·Due to start in: H2 2024 pending RC220 availability
·The value of bisantrene’s cardio protective effects is seen in physicians continued use of broadly acting chemotherapeutic agents, given that the vast majority ofpatients cannot have a targetable therapeutic mutation identified (through a mixture of poor biomarker and genetic testing availability and poor clinician uptake/understanding)
·VO2Peakidentified as a more appropriate surrogate endpoint for validation of cardioprotective effects vs. LVEF/GLT
oImportant distinction between VO2Peak as a marker of functional disability (impact on quality of life) and LVEF which is a poor indicator of cardiotoxicity and heart failure risk
·AML opportunity is still an important value-add for bisantrene but will take a backseat to cardio protection with anthracyclines in solid tumours, whichis a far greater and more valuable addressable market
·Investigator-sponsored trials will be utilised in AML as a cost-efficient way of building out the data package for RC220 in AML
1. Clinical Strategy
·Focus on proofof concept of cardio protection with anthracycline use in solid tumours first, before progression to P2 confirmatory trial that will aim to show the first sign of cardio protection +anti-cancer efficacy in humans with RC220
·Enable access to breakthrough and fast-track designations with FDA
I’m delighted to seethat bisantrene application in solid tumours is now the primary clinical focusof the company. Given the extremely large market potential in this therapeuticarea, it makes sense to go after this as focus #1. It is a clear contrast tothe previous strategy that continued to focus on development of AML which is afar smaller market.
2. VO2Peak as a newbiomarker for cardio toxicity in anthracycline patients
·Current standard-of-care measurements of heart damage neglect the significant andimmediate impact on quality-of-life that anthracycline-treated patientsexperience, which is a functional decline in exercise capacity and a burden on the activities of daily living
·Research suggests that these SoC markers i.e. LVEF and GLT are poorly correlated with functional capacity and long-term heart failure risk. It’s still important to reduce the risk of developing HF down the line but the impact of cardiotoxicity on a patient’s immediate quality of life cannot be understated.
·Anthracyclineexposure has a defined impact on VO2Peak and therefore a significant impact on patient quality of life
·VO2Peak represents a clinically relevant endpoint that can clearly show evidence ofbisantrene-mediated cardio protection and clinically relevant improvements inquality of life.
·Importantly, it seems as though VO2Peak can be measured in patients far easier than GLT or LVEF which requires the patient to undergo an echocardiogram, which is more invasive and has a higher burden on both patients and healthcare systems
I think the transitionaway from LVEF and GLT testing in favour of measuring VO2Peak as a biomarkerfor cardiotoxicity is extremely positive. It’s easier for patients and thehealthcare system, and provides a more well-defined prognostic indicator ofcardiotoxicity and seems to be more clinically relevant for patients. I’mhopeful that bisantrene will be able to demonstrate cardio protection throughmeasuring patient VO2Peaks during treatment in the trials. In total I think thismay be one of the most important bits of information in this whole update. Itis now clear how RAC plans to demonstrate improved cardiovascular outcomes inpatients treated with bisantrene & anthracycline combinations, withevidence behind the rationale, and in a format that physicians/institutionsshould be willing to participate with.
(20min delay)