Celsion Corporation (CLSN)

[sdtrond]

Been awhile since I posted here. Lol... think it was sub $3 last time.
I left a couple comments on the Seeking Alpha bear piece, this is the first of them.

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OK, time for a structured criticism of this article.

You have three main points, 1) Limited clinical experience with ThermoDox, 2) Phase 1 data fail to demonstrate a clear dose-response, and 3) RFA+ThermoDox responses are consistent with RFA alone.

For point #1, I cede the point that the ph1 was small, and as you say the HCC patient count was minute.
However, it was also on the basis of this trial, as well as animal studies that we are not privy to, that the FDA agreed to an SPA. While many SPA-granted trials fail, it is at least recognition that the trial data was meaningful.
Further, the NIH has designated HEAT a Priority Trial, again while meaningless for approval purposes, this is only one of 8 or so HCC trials granted this distinction out of the 400+ HCC trials currently underway.
Finally, you point out that only 1 patient in ph1 had HCC and tumor size > 3cm treated at 50mg. I admit this is an absurdly small size to bet a ph3 global trial. Fortunately, we also have the MLC patients which also showed a dose-response. We have ph1 data in recurrent chest-wall cancer which showed a 45% “clinically meaningful” response rate. We have buy in from Philips Healthcare which partnered to design a ph2 trial for palliation of painful bone-metastases. We have the company’s willingness to use precious dollars to begin the ph2 ABLATE trial prior to HEAT results, and begin enrollment in the ph2 section of the RCW DIGNITY study. Japanese partner Yakult agreed to pay an additional upfront payment in early 2011 in order to garner future lower royalty rates. Why on earth would they pay more than they had to now, if their best medical people thought it might fail, based on one such ph1 patient?

For point #2, you claim the ph1 data does not demonstrate a dose-response. However the study abstract concluded the dose-response was statistically significant – I am not quite sure how you manage to word your way around that.
The abstract also notes the median tumor was 3.7cm. So pairing that with the decision to enroll patients up to 7cm, which was driven by key opinion leaders, I want to point out 2 issues of why TDox+RFA should work in the real world (please see page 15 from the presentation poster available from http://bit.ly/UFI2P4: a) The cyctotoxic effect of dox is enhanced by heat. b) Dox reduces the ablation threshold temperature.
So we are releasing dox by heating the TDox IN the tumor tissue. I do not believe you are arguing that does not occur? Dox is more effective and the abalative zone increases because dox is present. It is not a very large jump to predict that larger tumors are naturally a better target.
And lastly, please see http://1.usa.gov/T5b8sS, where it states, “RFA/LTLD can treat Child-Pugh class A-B patients with tumors up to 7 cm, a substantial increase in curable patients.” Kindly note the word, “curable.”

Finally, for point #3, you argue RFA alone is as effective as RFA+TDox.
I love this! In your article, you specifically (sentence 3 under the section bolded, “Phase 1 data fail to demonstrate a clear dose response”) say, “The data clearly suggests that only HCC patients derive a benefit from ThermoDox therapy, while other liver metastases do not.” Regardless of other liver metastases, HEAT is HCC-only and you’ve here admitted these patients derive a benefit! Your own words kind of blows up your main thesis, hmmm?
Now, in the Wang et al study you cite, the most important statement is, “The ablative volume decrease was significantly greater for the RFA alone group than for the combination group (26.1 vs. 12.1%, p = 0.018).”
Really think about what this says. The combo group lost 14% less than RFA-only, a stat-sig result! In essence, you are arguing then the combination group DECREASED the effectiveness of RFA. Since you already ceded the point that HCC patients derive a benefit from Thermodox, this study is obviously totally inappropriate for comparison purposes. Another comment already notes that pegylated liposomal doxorubicin is not really comparable to Thermodix anyways…

Let me summarize your article back to you.
The ph1 trial was very small.
Fortunately the company had lots of preclinical data and an entirely understood MOA and already-approved drug to reassure the FDA that a jump to an SPA-granted ph3 was justified.
Fortunately the ph1 data was statistically significant in dose response, even though it was tiny! Trials that aren’t really comparable don’t show much correlation.

The only thing I agree with you on, really, is that you should not invest more on either the short or long side than you can afford to lose. I hope you’ve followed that on your short here.

Trond Hildahl