Curious Curis (CRIS) Pull-Back
Summary of Curis, Inc (CRIS) News
Curis announced on 11 June 2021 positive updated data from its ongoing phase 1/2 dose escalation trial of CA-4948 monotherapy in patients with relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at at the European Hematology Association 2021 Virtual Congress (EHA)
5 objective responses observed
The company plans to use 300 mg twice daily as the dose to measure efficacy (i.e. the recommended phase 2 dose, RP2D) in the phase 2 portion of the phase 1/2 study
The almost 37% drop in Curis stock price was likely in response to the to the 4 dose limiting toxicities (DLT) observed in the higher doses of 400 mg twice daily (two grade 3 rhabdomyolysis) and 500 mg twice daily (one grade 3 rhabdomyolysis and one grade 3 syncope) regimens
Impressions and Interpretation
The 5 objective responses observed, specifically the 1 complete response (CR), 1 complete remission with incomplete hematologic recovery (CRi) and negative minimal residual disease, 1 partial response (PR), and 2 marrow CRs, should give individuals interested in the company some comfort that CA-4948 is showing preliminary signs of potential activity
However, 3 of the 5 responses seen were in the 400 mg twice daily cohort which had the grade 3 toxicities
The drop in stock price can mean that the ‘street’ sentiment is ‘pricing’ into the company’s stock price the risk of CA-4948 not showing favorable activity or safety in the phase 2 portion of the study due to having to use 300 mg twice daily as the RP2D
Phase 1 studies give hints at what can be seen in the phase 2 portion of the study where efficacy is actually measures, so this all still looks like a dice roll to me
Short Write-Up
Curis is biotechnology company focused on the development of first-in-class and innovative therapeutics for the treatment of cancer. Its lead molecule CA-4948 is a first-in-class inhibitor of IRAK4 in oncology.
The company announced on 11 June 2021 positive updated data from its ongoing phase 1/2 study of CA-4948 monotherapy in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndromes, but in response to its announcement, the company’s stock dropped by almost 37%. You can read the full press release or listen to the webcast for more details, but the drop in he stock’s price was likely due to the DLTs seen in the phase 1 dose-escalation study.
I want to emphasize the ‘dose-escalation’ because the primary goals of the phase 1 portion of studies such as these is to ultimately find out the highest maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to get an initial sense of the safety profile and possible adverse events to expect in the future. Other objectives of these phase 1 studies can include getting an initial read on what type of activity we may see in the phase 2 portion of the study as well as any pharmacokinetic (PK), pharmacodynamic (PD), or biomarker related data.
The recent data update from Curis on CA-4948 demonstrates that the phase 1 portion of the study accomplished its objectives. Now one needs to ask what this all means. In short, CA-4948 has demonstrated that it has signs of activity as evident by the objective responses seen and, ironically, the toxicities seen in the 400 mg twice daily and 500 mg twice daily doses. Of note, the PK data from the webcast showed that even at 300 mg twice daily doses CA-4948 was hitting a 98% target inhibition — meaning the molecule is doing what it was made to do (good). The problem with all this is that the RP2D for the phase 2 portion of the study is 300 mg twice daily and of the 5 objective responses seen one of those responses (the CRi) was seen in the 300 mg twice daily dose, while the other response (mCR) was seen in the 200 mg twice daily dose. The “street” is likely ‘pricing’ in the risk that CA-4948 does not show favorable efficacy and safety in the phase 2 portion of the study. Of note, the 200 mg twice daily and 300 mg twice daily doses had participants that experienced stable disease which one could say is promising since the participants enrolled in this study were heavily pre-treated and were later in line. This could be good since CA-4948 was able to illicit responses and/or cause tumor to not grow further or shrink in participants who were already beat up badly by AML or MDS.
Conclusion
Phase 1 data from CA-4948 is promising due to the molecule’s ability to illicit responses in AML/MDS patients that were trashed. However, the ‘street’ is scared and is getting out of Curis stock because of concerns on the future of unfavorable efficacy and safety to be seen in the phase 2 portion of the study, which is yet to actually be understood in the phase 2 portion of the study. I acknowledge I have not looked at the full landscape of competition or have done a deep dive of the molecule or the company, but I speculate that if and only if efficacy and safety data seen in the phase 2 portion of the study is favorable, then expect Curis to likely head towards an accelerated development pathway to approval and probably see a rebound in company’s stock back towards is pre-announcement price of $12 per share.
The question of whether Curis should be valued at $12 per share or not is a different story.
Author’s Note
This is a post that shares my thinking on trying to understand what the heck went on with small biotech and pharmaceutical companies I read about. I ultimately am testing my own understanding of what I read.
If you enjoyed this short write up and/or would want write-ups like this on small biotech/pharmaceutical company you may be interested in, then let me know!
Disclosure
I do not own CRIS stock. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it from any related parties mentioned in the article, directly or indirectly. I have no business relationship with any company whose stock is mentioned in this article.
