Specialist
Senior Scientist at Dana-Farber Cancer Institute
Agenda
- KRAS G12C inhibitor market, targeting lung and pancreatic cancers
- Amgen (NASDAQ: AMGN) and Mirati's (NASDAQ: MRTX) product offering and clinical trial involvement
- Patient population by disease and tumour type 4. 3-5-year outlook, focusing on potential for similar inhibitors targeting other cancers
Questions
1.
Can we start by outlining key challenges and advances in the KRAS field over the last 6-12 months?
2.
You mentioned the oncologic conditions in which G12C is now being analysed. Can we examine the patient population across lung, colorectal and pancreatic, plus opportunities for further applications?
3.
Where did Amgen and Mirati stand out in their data readouts for G12C vs the past attempts which were relatively unsuccessful?
4.
Where do you think Mirati could have an advantage over Amgen in G12C? Dependent on Amgen’s readouts, how do you think the products will compete in the market, accounting for oncologic conditions or stages regarding application, and that drawing upon that patient population we discussed?
5.
Can you elaborate on the implications of the anti-tumour effect with the MEK inhibitors? This potentially indicates that Amgen’s 510 product is not effectively shutting down the G12C pathway. Do you think that puts Amgen at a significant disadvantage vs Mirati?
6.
Can we explore potential endpoints in Amgen’s upcoming 510 readouts in ASCO, and what could be a successful vs unsuccessful response rate? There was some disagreement on trial design at the last conference, whether there should be waterfall plots conducted for Amgen or Mirati.
7.
Can you outline the preclinical tools that will be used to address the G12C inhibitor resistance, examining models such as PDX [patient derived xenografts], cell lines, mouse models, etc?
8.
What are your thoughts on new clinical approaches to KRAS, such as the cRNA approach for pancreatic and the mRNA from Moderna?
9.
You mentioned AstraZeneca’s KRAS treatments. What about the Eli Lilly or Johnson & Johnson products? How would you evaluate the Lilly combination with Merck for breast and lung cancer?
10.
Is there any early indication that Novartis’s and Eli Lilly’s near-iteration for G12C on the pharmacokinetics side could rival Amgen and Mirati? Could it serve as a complementary base?
11.
What timeline could we expect for the pharmacokinetic formulation of the Lilly and Novartis G12C iterations?
12.
You mentioned KRAS treatment alternatives. Can you elaborate on the downstream effects for the MEK and the ERK inhibitors? What is being analysed there?
13.
Can smaller dosage successfully be used in a combination KRAS treatment with lower toxicity effects, or is this still in an experimental stage?
14.
Is there anything you would like to elaborate on from our discussion so far on Amgen, Mirati and the KRAS sector?
15.
You mentioned the endpoints’ toxicity being key for Amgen and Mirati and the upcoming Asco conference. Are there any other hypothetical endpoints that we should be paying attention to, that you think carry equal value? Anything that could surprise us there?
16.
Could we get your 12-18-month outlook for Amgen in terms of the KRAS sector? Anything that we should be monitoring particularly closely, or that you find is frequently misunderstood?
