Biotech Values

[DewDiligence]

Maybe journalism is simply more fun than
managing a portfolio. Feuerstein seems to
be having a jolly good time exposing the
long-running INGN scam.

http://www.thestreet.com/newsanalysis/biotech/10342959.html

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Introgen's 'Promise'

By Adam Feuerstein
3/7/2007 12:03 PM EST

Introgen Therapeutics (INGN) has accused me of being "false and misleading" because of some sharply worded columns in which I detail the ways the company has misled investors about its development of the cancer gene therapy Advexin.

So far, Introgen hasn't detailed how I've been false and misleading, and the company has never contacted me or asked TheStreet.com for a correction. But on Thursday, Introgen will hold a conference call to discuss its fourth-quarter results. On that call, the company has promised to comment further.

Good. It should be a fun call. To get ready for it, I read through transcripts of Introgen conference calls going back four years. Below is a timeline of sorts, complete with excerpts that detail the many ways in which the Advexin story has changed over the years.

Investors would be well-served to acquaint themselves with this timeline before Introgen management speaks again on Thursday.

Here's Max Talbot, Introgen's regulatory chief, speaking on the company's second-quarter 2003 conference call on Aug. 12, 2003:

"As discussed in previous calls, it is our plan to file the BLA for Advexin and head and neck cancer in 2004."

Then, David Nance, Introgen's president and CEO, speaking on the company's fourth quarter 2003 conference call, held Feb. 27, 2004:

"We are moving closer to our goal of filing a BLA -- Biologic License Application -- for Advexin later this year."

On Introgen's first-quarter 2004 conference call, held May 11, 2004, the Advexin filing story changed. Here's CEO Nance (emphasis added):

"With respect to our lead product Advexin, we remain on track to begin the BLA submission this year."

On the same call, SG Cowen biotech analyst Joshua Schimmer asked:

"As far as when you expect to complete the BLA filing, if you're going to start in '04?"

To which Talbot replied:

"We will initiate the submission this year though. We talked about that for quite a while and we're still on track for that."

On an Aug. 12, 2004, conference call, Talbot tried to offer more clarity on the Advexin filing strategy:

"... We remain on track with the initiation of the submission of our BLA this year. We anticipate completion of the submission review process will take approximately one year."

Fast-forward to the end of 2004: Did Introgen succeed in "initiating" the BLA process for Advexin?

Nope. On Dec. 23, 2004, the company announced instead, via press release, that it had "filed a request with the U.S. Food and Drug Administration to accept a 'rolling Biologics License Application' (rolling BLA) for Advexin."

Elaborating further on a March 14, 2005, conference call, Talbot tried to explain how missing the company's deadline to actually complete an Advexin filing in 2004 -- and also failing to achieve its amended guidance to simply begin the filing process in 2004 -- was, in fact, a good thing:

"Throughout the development of Advexin, we have worked very closely with FDA in an effort to follow the dictates of the agency so that Introgen could consider the most expeditious approach to the registration of this fast track for product.

"It is now our responsibility to take advantage of emerging regulatory and clinical opportunities to speed the introduction of Advexin, and we are doing just that. ... We saw an opportunity to possibly reduce the time of review of the approval process by initiating an accelerating approval registration, primarily on the basis of these phase II findings."

On Aug. 9, 2005, Introgen held a conference call to discuss its second-quarter 2005 financial results. It had been 12 months since the company said Advexin's "submission review process will take approximately one year." Perhaps Advexin was finally in the hands of the FDA?

Unfortunately, no, explained Introgen's Talbot:

"We are in ongoing contact with the U.S. Food and Drug Administration and are continuing to implement the regulatory plan that we described at the time of our biologic license application -- BLA -- request to the agency in December 2004."

Right. In December 2004, Introgen had asked the FDA if it could submit a "rolling BLA" for Advexin. Eight months later, had the FDA said yes to Introgen's request?

Introgen never said a word about it.

Moving right along to Introgen's third-quarter 2005 call on Nov. 9, 2005: Once again, the Advexin-FDA story veered onto another course. Talbot announced that Introgen's registration approach for Advexin was now based on using the "'targeted for selective approval' paradigm that is the current focus of FDA's consideration for the evaluation of breakthrough cancer therapies."

Later on the call, Talbot explained:

" 'Targeted for selective approval' is a registration strategy that utilizes continuing and exhaustive data reviews to determine which patients are most likely to benefit from a new therapy on the basis of molecular mechanisms and other physiological and clinical parameters."

Talbot then referred to an article in the New England Journal of Medicine that discusses at length this new regulatory approach being used by the FDA to review and approve new cancer drugs.

But there was one problem -- the " 'targeted for selective approval' paradigm" doesn't exist. In the July 29, 2004, New England Journal of Medicine article referenced by Talbot, authors Dr. Thomas Roberts and Dr. Bruce Chabner are very clear that this new paradigm is their idea, a suggestion to the FDA. The agency hasn't considered it formally, let alone started to use it to approve drugs like Advexin.

By December 2005, the year was almost over, and just like in 2004, Advexin wasn't close to reaching the FDA. With the clock winding down, Introgen shifted gears once again.

On Dec. 22, 2005, the company announced that it had asked the FDA for permission to "accelerate the initiation of an interim analysis of its randomized, controlled phase III Advexin clinical trial data ahead of schedule."

The FDA agreed, said Introgen. The plan called for data from the analysis to be submitted to the FDA to "advance Advexin's regulatory submissions," said Introgen's Talbot in the release.

But what happened to Introgen's earlier request, in December 2004, asking the FDA to accept a "rolling BLA" for Advexin? Twelve months had passed -- surely the FDA must have responded, no?

It's a mystery, because Introgen was mum on the subject.

On March 14, 2006, Introgen held a conference call to discuss its fourth-quarter 2005 results and discuss in greater detail this new "agreement" with the FDA to analyze data from its phase III trials. But during the Q&A session, one caller was more interested in learning when Advexin would finally be filed with the FDA.

"The first question I have is when are you going to file the last section of the BLA for Advexin," asked the caller.

Introgen CEO Nance replied:

"Max [Talbot] , you can comment if you want to. It will be brief, I'm sure, but we're not giving particular guidance. As you know, a BLA is completely filed when all sections are in. We are providing data to the agency sequentially. We have pending requests for accelerated approval. We have a confirmatory trial strategy that is coming into place that Max described to you with our interim efficacy analysis on phase III. I don't think there is an answer that we can give you for that particular question."

Jumping again to December 2006: It was the end of another year without Introgen finishing the job of filing Advexin to the FDA. In fact, it wasn't even clear whether the company had started anything. And we still didn't know if the FDA ever responded to Introgen's request -- now two years earlier -- to file a rolling BLA for Advexin.

After talking again on Dec. 28, 2006, about analyzing the phase III trials of Advexin (which, by the way, began in 2000 and have never completed patient enrollment), CEO Nance was asked for a rough timeline.

"To respond to your question, the phase III analysis will begin early in 2007," answered Nance. "Before the end of the year, we expect for all of the analysis and filings to be complete. Max Talbot can elaborate on that. But in terms of the timing, we know when we'll begin the process, and we're not providing any specific guidance on when we will conclude specific parts of the process."

Talbot did elaborate:

"We believe that corroboration of our phase III results with these prospective Phase III analyses will support Advexin licensure in the U.S., either via the accelerated or full approval regulatory procedures. We look forward to providing you with additional updates as we complete our U.S. and European regulatory filings in 2007."

That sounds like a promise -- an Advexin approval filing in 2007. Will Introgen make this deadline? Perhaps we'll find out on Thursday afternoon. Let's hope the company does better than it did in 2004, 2005 and 2006.
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