As we continue the search for early stage biotechs that might be worth a look, the ascension of yet another PD-1/PD-L1 axis inhibitor might not be very exciting, especially given the formidable competition from pharmaceutical giants like Pfizer (NYSE:PFE), Bristol-Myers (NYSE:BMY), and Merck (NYSE:MRK). However, Curis, Inc. (NASDAQ:CRIS) has made the first forays into clinical research using a novel, orally delivered PD-L1 inhibitor.
As I wrote in a previous article, CRIS is currently hedging most of its efforts on CUDC-907, a histone deacetylase-PI3K inhibitor that has shown some promising remissions in heavily treated DLBCL. I also wrote about favorable preclinical data presented by the company at this year's AACR meeting for its other major contender, CA-170.
I stated in the article that CA-170 development does not factor at this time into my personal due diligence, as it has not reached clinical development.
Today, CRIS has announced that it has dosed the first patient in its phase 1 clinical trial for CA-170.
And so my interest spikes! What's the deal with this drug?
CA-170 has two principle differentiating features from competitor PD-L1 inhibitors like atezolizumab and avelumab.
1) CA-170 is an orally bioavailable agent, with preclinical evidence suggesting similar activity to emerging PD-L1 inhibitors.
It is difficult to overstate what a huge difference an orally deliverable agent can make for patients. On one hand, many patients would prefer to take a pill than an injection.
More importantly, however, oral medications are the most convenient way to provide patients with so-called "maintenance" care, whereby you give a tolerable dose to the patients that they take each day. In patients with CML, they can go on taking Gleevec every day, and the therapeutic benefit persists for as long as they continue treatment.
Will this be the case with immune checkpoint inhibitors? It's impossible to say at this point, but an orally available version of these agents allows the question to be addressed.
For CRIS, there is also the convenient fact that maintenance therapy needs to be taken indefinitely and regularly, which smoothes out the revenue stream.
2) CA-170 also targets VISTA, another immune checkpoint
Currently, some speculation exists as to whether we can improve the efficacy of immune checkpoint inhibitors through combined inhibition of multiple checkpoints. This is already underway with combinations of CTLA-4- and PD-1-directed agents.
To date, VISTA remains a proposed therapeutic target for combination with PD-1 inhibitors, but it has not been validated.
By targeting both VISTA and PD-L1, CA-170 may have a built-in, synergistic dual-targeted mechanism of action. It is possible this will improve response rates and disease control.
Of course, that is speculative and based on preclinical findings from cell biology. But it was worth noting here because it illustrates how one might differentiate CA-170 from the rest of the pack.
When does the rubber hit the road?
Phase 1 trials are all well and good, but if CA-170 is going to be successful, it still has years of development left. Prospective investors are going to want to watch out for news of this study, and perhaps we'll get our first glimpse in 2017 of the safety and efficacy signals.
That said, immune checkpoint inhibitors have benefited greatly from accelerated development timelines; the approval of nivolumab in melanoma came only 2 years after the first presentation of phase 1 data at ASCO 2012.
If CA-170 represents a safe improvement on other agents, then we'd best watch out for Curis. With sales of its approved drug Erivedge growing, the company has approximately 2 years' worth of operational funds on hand to continue this research, in addition to its dual HDAC/PI3K inhibitor.
Take these facts together, and I think you have a compelling case for the discerning investor to take a deeper look at Curis.
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Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.