Replies to post #178694 on NorthWest Biotherapeutics Inc (NWBO)

[trocprofit]

bingo...

[sentiment_stocks]

You probably weren't around when rindopepimut with its break-through peptide brain vaccine that was going to change the way recurrent and newly diagnosed GBM were treated.

Rindo targeted EGVRv3, which, like survivin, is also found in the tumors of a significant number of GBM patients.

In fact, here's exactly what Adam Feuerstein had to say about Celldex's rindopepimut, back in February 2015.

For those who missed the news from earlier this week, the U.S. Food and Drug Administration granted Breakthrough Therapy Designation to Celldex's rindopepimut for the treatment of patients with EGVRvIII-positive glioblastoma, an aggressive form of brain cancer. Celldex also tagged rindopepimut with the brand name Rintega.

The simple answer to your question is yes, Rintega's odds for FDA approval are improved with breakthrough designation. What I like best about the news is that Celldex filed for breakthrough designation after a meeting with FDA to share the positive, interim results from the Rintega "ReAct" phase II study in recurrent glioblastoma patients. The FDA's affirmative decision on the breakthrough request suggests regulators were encouraged by the ReAct data and will be more amenable to accept and review Rintega for accelerated approval.

A lot of things need to go right first, but you can put together a plausible scenario under which Rintega is approved in the middle of next year. That's potentially huge for Celldex.

I wrote about the positive, interim results from the ReAct study last November when the data were presented.Rintega plus Avastin significantly delayed tumor progression and prolonged overall survival compared to Avastin alone. The patients enrolled in the study has recurrence of EGVRvIII-positive glioblastoma but had not yet been treated with Avastin.

Celldex designed the ReACT study to be exploratory, meaning it wasn't intended to be strong enough to support a Rintega regulatory filing. But as recounted on its conference call Tuesday, Celldex met with FDA to share the interim Rintega ReAct data and begin discussions on the possibility of using the study as the basis for a regulatory filing.

Celldex's Chief Medical Officer Tom Davis:

First, we have been in initial and formal discussions with the FDA, which led to our decision to apply for Breakthrough designation. We believe the FDA's decision to grant this designation underscores Rintega's therapeutic potential for patients with glioblastoma and speaks to the potential clinical relevance of this particular subset. We have been very candid about the fact that bevacizumab [Avastin] naïve group within ReACT was not designed to be an approval study, but given the dearth of treatment options for patients facing this disease and a statistically significant survival benefit the study demonstrated at the interim, with the urging of our investigators, we feel that we have an obligation to patients to formally discuss the final data set with the regulators assuming that it remains consistent.

Final results from the Rintega ReAct study will be ready for presentation in June at the annual meeting of the American Society of Clinical Oncology (ASCO). If the interim results hold up, Celldex will go back to FDA and seek permission to submit Rintega for accelerated approval in recurrent glioblastoma, supported by the ReAct study results.

If FDA says yes (and the granting of breakthrough status suggests the agency is already leaning in that direction), Celldex could probably complete an FDA submission in early 2016. Historically, FDA reviews breakthrough status drugs with alacrity, which means Rintega could be approved in the middle of 2016. If you want to be more conservative, maybe approval happens in the third quarter. Regardless, Rintega makes it to the market much faster than most people ever expected.

The ongoing phase III "ActIV" study of Rintega in newly diagnosed glioblastoma patients (enrollment complete) could serve as the required confirmatory study to backstop the accelerated approval.

Celldex executives couldn't speak with me this week to confirm (or throw cold water) on my bullish Rintega scenario because they were on lockdown finalizing a follow-on public offering of 7.25 million shares at $24 per share. The sale nets the company $164 million, which could balloon to more than $200 million if the over-allotment is sold.

At the risk of sounding too optimistic (and so unlike my normally skeptical self), Celldex had a great week with breakthrough and the successful stock offering. The middle of the year will be super busy with the final ReAct data, a go/no-go interim analysis from the Act IV study and the FDA meeting on an early Rintega filing. There's a lot to like about Celldex and I didn't even mention the rest of the company's cancer immunotherapy pipeline. I'm loathe to praise a New York Giants fan (and a Patriots hater), but Celldex CEO Anthony Marucci is on a roll.

https://www.thestreet.com/story/13060528/1/biotech-stock-mailbag-receptos-celldex-therapeutics-exact-sciences.html

So hopeful. So glowing.

And you know, most of the patients in the newly diagnosed P3 trial (that failed) which is not the one described above (that also failed) did not show any EGFRV3 when their tumors returned. So it got rid of the EGFRv3, but not the tumor.

Of course, going after a single antigen or a single protein, isn't going to stop GBM from returning. IMUC's ICT-107 targeted six other proteins (guess what? they also show up on a good number of GBM tumors: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13Ra2) and they had to stop that trial for lack of funding. ICT-107 did decently well for patients with HER-2 (flipper thinks it should have been approved for that), but ImmunoCellular (IMUC) had to wind down their P3 trial for lack of funding. They just weren't able to demonstrate any sort of real efficacy.

So perhaps this Survaxm will surprise us and work brilliantly well, and surpass DCVax-L's year-old, blended data (including the control arm), or eventually surpass the unblinded treatment arm data, which targets everything in the each patient's own, specific tumor, in the treatment of GBM.

But you may want to consider the two example's I've given here of two other vaccines, one which Adam absolutely adored, that targeted both one and six similar proteins, before you get all googly-eyed about Survaxm.

You may want to consider too, that the paper you are reading about these results in - BioWorld - is hardly a peer-reviewed journal. The link on Mimivax to BioWorld takes you to a sales sheet with a telephone number to Clarivate Analytics, and it seems they are looking to raise money to help keep the trial and the company going. BioWorld is Clarivate Analytic's own special journal.

If you are looking to help them fund their single protein GBM vaccine, here is the number to Clarivate Analytics:
For Sales Inquiries: http://clarivate.com/life-sciences/news/bioworld/#. NORTH AMERICA, Tel: [phone].