In my final post from the 2013 annual meeting of the American Association for Cancer Research (AACR), I wanted to share some more reflections from my time in the poster sessions. It’s certainly not all mice, and test tubes, and there were some interesting data from biotechnology companies to consider.
Sometimes the data presented is completely new, other times if you are following a product or company you can see the next stage of development and track progress. AACR posters are often not available if you don’t attend the meeting.
Additionally companies use AACR to showcase potential early licensing opportunities and new targets, so like Bitcoins a few nuggets can be mined from the meeting. Here are a few examples of what the AACR poster sessions had to offer from a biotech perspective.
Gilead $GILD – Following a new combination
At the 2012 American Society of Hematology (ASH) annual meeting in Atlanta last year, Russell Burke and colleagues from the Knight Cancer Institute at OHSU (Brian Druker’s lab) presented a poster (abstract 3876) on the rational for Combining idelalisib (GS-1101/CAL-101), a PI3 kinase delta (PI3Kδ) inhibitor and a novel highly selective Spleen tyrosine kinase (Syk) inhibitor, GS-9973. In their abstract they noted that,
“Simultaneous inhibition of multiple pathways downstream of the BCR [B-cell receptor] has the potential to result in a synergistic response that may overcome the resistance observed with single compound use”
Furthermore, they also demonstrated that,
“both PI3Kδ and Syk inhibition reduces CLL survival” and that “combination therapy targeting both PI3Kd and Syk may provide a novel treatment approach, especially in patients with poor risk disease that may not respond optimally to single agents.”
This year at the AACR annual meeting, a Gilead poster (abstract 26) evaluated the safety, pharmacokinetics and pharmacodynamics of this combination in female healthy subjects. The poster concluded:
- Co-administration of GS-9973 with idelalisib displayed markedly higher PD effect vs. either agent alone.
- Overall, GS-9973 and idelalisib were well tolerated when administered in combination or alone.
- Phase 2 studies in B cell hematologic malignancies evaluating GS-9973 + idelalisib are ongoing.
We will most likely have to wait to ASH meeting later this year in New Orleans to see what the clinical benefit of this combination is, but you can see how you can follow progress from a poster at ASH, to a poster at AACR and then a phase II or III clinical trial presentation at ASH or ASCO in the future.
Ariad $ARIA – a new potential target for ponatinib?
Ponatinib (Iclusig) is a multi-targeted tyrosine kinase inhibitor (TKI) of several targets including Bcr-Abl, FGFR, ALK and RET. Several posters were presented at AACR last week. In one that caught my attention (abstract 2084), Ariad researchers showed it is a highly potent inhibitor of activated variants of RET Kinase, which is often dysregulated in medullary thyroid cancer (MTC) and non-small cell lung cancer (NSCLC).
Vandetanib ($AZN) and cabozantinib ($EXEL) are other multi-kinase inhibitors that received FDA approval in the last year or two for MTC, albeit in different lines of therapy, so the activity of other TKI’s in MTC should not come as a surprise.
The Ariad poster demonstrated the preclinical activity of ponatinib over other TKI’s in variants of RET in MTC and NSCLC. The poster concluded:
“These results provide strong support for the clinical evaluation of ponatinib in patients with RET-driven cancers.”
From a scientific rational the above statement makes sense, but from a commercial perspective it’s more questionable if this were the lead indication. However, it could make strategic sense to add on small niche indications for a compound that is generating its primary revenue elsewhere.
The challenge is that the medullary thyroid cancer market is not large especially in the relapse setting, as Exelisis have found, plus the tumour is a slow growing one. While NSCLC sounds promising, the number of NSCLC patients with RET is small (~1%).
This means it will most likely require the screening hundreds of patients to find one patient with RET into a clinical trial, assuming they are willing and meet the inclusion criteria. This is likely to be an expensive and time-consuming process, so the commercial rational will need to be carefully considered.
BioMarin $BMRN – a prostate cancer licensing opportunity or a “dead donkey”?
Companies also use posters at AACR to showcase potential licensing opportunities and one example I came across was BioMarin’s poster (abstract 2049) for BMN860 a novel CYP17 inhibitor. Based on some limited preclinical data that showed BMN860 to be more potent than abiraterone acetate (Zytiga), the company are seeking to license out their compound.
Interestingly, the BioMarin poster showed no data comparing BMN860 to other second-generation CYP17 inhibitors such as TAK-700 (orteronel), and the presenter admitted they had no plans to do further preclinical work on it themselves.
Given the costs of bringing a new prostate cancer drug to market and the uncertainty of the market opportunity in the face of generic abiraterone and competition from other CYP17 inhibitors far head in development, it’s hard to see the commercial opportunity for BMN860.
If you are a Pharma BDL professional looking to in-license a novel CYP17 inhibitor, then BioMarin do have one on offer. However, for those used to British vernacular, it struck me as a “dead donkey” being too little too late to really capitalise on the market opportunity.
This is the end of my coverage of AACR 2013. I am looking forward to the AACR-EORTC-NCI Molecular Targets and Cancer Therapeutics meeting in Boston later this year. Given the focus of Boston biotech on cancer drug development, I expect this to be a high quality meeting.
If you are interested in more coverage from AACR 2013, I encourage you to check out Pharma Strategy Blog, which will have some in-depth pieces in the coming days.