Therapeutics


Table 1: Lessons from MD Anderson Therapeutics Discovery


Focus on your patients; they are your shareholders and their survival is your bottom line Prioritise intimacy and immediacy, breaking down silos between clinicians, researchers and patients Start with the bench at the bedside, with each patient and their cancer Foster an environment that encourages collaboration across teams and disciplines Bring in professionals who have a multifaceted understanding of drug development


You never know where the next breakthrough idea is coming from; be prepared to invest time in exploring ideas from potential collaborators


Clarify the drug discovery process to potential collaborators; explain why rigorous target validation is required and why certain experiments are defined as go/no-go experiments


Assemble the best team to make projects successful and bring in additional external collaborators/partners if resources are required Develop a ‘ruthless’ mindset when it comes to culling less-promising agents in development


Be open to a change of course along a project’s development path; a programme might have more clinical impact elsewhere Every programme needs a champion(s) Aim for therapeutic targets that improve patient care rather than the bottom line


Although conducting research and clinical trials in-house has marked benefits for drug development, leverage external capabilities with CROs and CMOs when needed to improve efficiency


be developed from concept to clinical trial by the Therapeutics Discovery division, advancing to the clinical setting within 18 months of its identifica- tion. It is the product of an extensive medicinal chemistry campaign of lead optimisation to engi- neer in the molecule all the properties required to make it effective for use in humans. We have recently published the results from initial preclini- cal studies of IACS-10759 showing that, in models of AML and brain cancer dependent on OXPHOS, this agent reduces tumour growth through inhibi- tion of cellular proliferation and induction of apoptosis at well-tolerated doses6. In another pre- clinical study by Lissanu Deribe and colleagues, IACS-10759 was demonstrated to have benefit in types of lung cancer characterised by mutations in the SMARCA4 gene7. Cancer cells with this muta- tion show an increase in respiratory capacity and oxygen consumption, increasing their vulnerability attack by agents such as IACS-10759 that inhibit OXPHOS. IACS-10759 has now advanced to Phase I clinical trials in relapsed/refractory AML, supported by the Leukemia and Lymphoma Society, and in solid tumours.


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Summary of lessons we have learned Many of the lessons we have learned about drug development are summarised in Table 1. It should be noted that some of these lessons are not trans- latable to pharmaceutical companies guided by a shareholder model of corporate governance, nor can they be easily implemented at smaller academic centres lacking the advantages of scale of major cancer centres such as MD Anderson. Above all else, we have learned that a patient-guided approach must underlie all that we do, starting with identifying the most compelling patient needs at our centre and working in close proximity to our patients to continually improve drug develop- ment. Aligned with this approach of breaking down walls between healthcare professionals and patients is the urgency of removing silos between clinicians and researchers that have historically hindered drug development. Because the Therapeutics Discovery division at


MD Anderson is not driven by profits, we are able to focus less on drugs that improve the bottom line and more on those that improve patient outcomes, including in patients with rare tumour types that


Drug Discovery World Fall 2018


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