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Right - Thanks for the helpful DD BigK - saves me time putting it together myself.
Folks should realize (and you've indicated) there are some assumptions necessary as there are a few possible approaches NNVC could take and there are inconsistencies in some of the FDA guidance (the general FDA guidance for FDA ICH M3 (R2) "Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals" has different requirements and emphasis than the specific FDA guidance for preclinical studies for "Antiviral Product Development").
Very helpful for folks on the board with less familiarity with the industry practices and regulations.
Right, David, SP is matching XBI DESPITE bogus arguments.
Things are lining up for re-acceleration in SP in Biotech sector and NNVC.
Many potential catalysts for NNVC SP in the very near term:
1. Completion of new plant for clinical materials and further R&D - communicated as Summer 2014
2. Completion of materials and start of preclinical animal testing for remainder of Toxicity, PK/PD, Efficacy studies - my estimate is a series of PR's over next 2 months.
3. Contract with ViroClinic for multiple tests - H7N9, MERS, Dengue, etc. - ANYTIME
Just a few coming soon. Don't fight the tape or the momentum.
Right - and the false generality that one example in years of multiple awards implies all the awards are a scam doesn't track with logic.
By that logic, the Grammy awards watched and followed by millions are a scam and all the artists are scams because one scam, Milli Vanilli, won best new artist in 1990.
Yeah - right...
Cheers!
You're a good egg, Nanopat. Cheers to you for the longest tenure on the board and your technical and patent knowledge and research. It pains me to see your frustration with the SP. I share it too. But hope shines through in the sound technology and the progress over the last year. IMHO the rest is noise.
All it takes for evil to win is for good men to do nothing.
Drs. Seymour and Diwan are doing the good work. NNVC will succeed. Neither the science nor the data have changed. There has been NO Toxicity of any nanoviricide yet with extensive testing. FluCide saved 100% of the mice after infection with a lethal dose of the flu that killed 100% of untreated control mice.
Not all of us post here everyday because to be honest it is depressing to read the crap posted as evidence here.
The stock will go up and down but near-term, progress continues to be made.
I have been saying for a long while now that I expect the start of the remaining Toxicity Studies to begin by end of Q2.
Tox, along with the efficacy studies at ViroClinics, PHE and/or LRRI provides the broad spectrum Flu indication that will gain approval for sale in Australia TGA, then EU EMA, then US FDA starting most likely Q1/Q2 2015.
If the stock goes low enough, I may buy some more at stink bids. If not, the wait, with the light so close now at the end of the tunnel, is not too much for me to wait for.
But management needs to come through on meeting the timelines for the early FluCide milestones - for me that is June 2014 for remainder of Toxicity study to start.
Range-Finding non_GLP Studies are standard industry practice.
The reason labs provide information on this service is BECAUSE it is standard industry practice per Changes_IV source.
But if that isn't good enough LASA is an industry practice group who has published guidance on Range-Finding Toxicity studies.
LINK: LASA Guide on Dose Level Selection for Regulatory Toxicity Studies
Also, discussed in detail in the posts below:
LINK: Post 85041
LINK: Post 86638
It is not only standard industry practice to do Range-Finding studies before more rigorous Regulatory Toxicity studies. It is also smart development (to know the effects and tests needed, the dosing levels, etc). And it is also wise use of company resources (to not waste money doing the much more expensive GLP Regulatory Tox studies twice).
Definitely will be sending to SEC, Stockbuilder!
~1million shares failed to deliver before PT libel article!
I just started doing a little more DD after Leifsmith's and Diabolical Southpaw's previous posts on the Dendreon sudden price spike example (Thanks for that!).
There were ~1 million phantom shares in NNVC that failed to deliver before the PT libel article. Those non-existent shares diluted shareholders and contributed greatly to the share price drop. A small amount of shares that fail to deliver is not unusual for liquidity reasons. But this amount, strategically put up against legitimate short and long shares look like they were (and are being) used to manipulate the stock price and thwart true price discovery.
Bottom line is that NNVC has been chosen for this stock manipulation for the following reasons:
- Not because of problems with the science, management or progress
- But because the BioTechs are easier target with science-illiterate weak hands
- And because new bio-technology is a challenge to develop
- AND, because NNVC has consistently been tightly held with "hard-to-borrow" shares and what had been a low churn rate volume that could be more easily manipulated with fewer shares.
- And had an attractive market cap to extract value from.
- And all developmental (before commercialization) biotech startup companies always have some non-material (to the SP) issues that can be exploited and trumped up by manipulative interests.
Note that I AM NOT talking here about normal short and long sales which are legal. I am talking about excessive phantom (naked short) shares which are not delivered in the statutory 3 day time frame.
I have done a search and find on NNVC FTD from the SEC website and copied the results at the bottom of this post.
LINK: SEC.gov Failure to Deliver
Note in particular the 882,616 shares that failed to deliver by Jan 24 and ask yourself - would the share price have dropped as much on Jan 21 (and later) without those phantom shorts to push against the 2,848,000 that would normally have traded without the extra phantom shares. This amounts to over 31% of the volume that would have traded that day.
In total, there were around 1 million shares that failed to deliver in the month before the PT libel article setting up for that hit piece.
More subtle, but more important to price recovery were the nearly 30,000 shares (~10x to 100x greater than normal in that timeframe) that failed to deliver on Feb 28 which were supposedly "borrowed" on Feb 25. This date is key as the stock was making a steady rise to fill the gap after the PT libel article. Without those phantom shares sold at strategic points throughout the day, there would have been less than 300,000 shares sold. Over 10% of the shares sold that day were non-existent and not delivered in the 3-day statutory requirement. If you notice the candle for Feb. 25, the stock was driven down after it had rallied on the continuing trend to fill the gap. This is highly suspicious.
So the claims about loss of value appear more related to what very well may be illegal stock manipulation than any real or perceived loss of value in the company. Remember, institutional investment keeps increasing, there has been insider buying, and there has been great continuing strong support by longs here.
What does that mean for the share price going forward? I think we can count on continued price manipulation in the short term. But it will be difficult to continue to do so under the radar of the SEC Reg SHO statutes when the company begins to release expected news on Regulatory Tox testing, efficacy studies at ViroClinics, PHE and LRRI and the completion of the manufacturing plant. These announcements could begin any time, but are likely by mid summer.
If you are worried about continued price manipulation, note the SEC Reg SHO statutes have additional reporting requirements when these "Failures-to-deliver" shares run for 5 consecutive days or more. This would add more scrutiny and suspicion after the many complaints of individuals on this board to the SEC regarding what seems to be a criminal stock manipulation. This investigation is much more important than the civil action that NNVC is letting its lawyers handle while they continue to develop their life-saving technology.
Good Luck to all longs.
1st Half Jan 2014
DATE CUSIP Ticker FTD Shrs Company Share Price
20140103|630087203|NNVC| 14|NANOVIRICIDES, INC. NEW COMMON|4.95
20140107|630087203|NNVC| 414|NANOVIRICIDES, INC. NEW COMMON|4.88
20140108|630087203|NNVC| 389|NANOVIRICIDES, INC. NEW COMMON|4.96
20140109|630087203|NNVC| 200|NANOVIRICIDES, INC. NEW COMMON|4.91
20140113|630087203|NNVC| 680|NANOVIRICIDES, INC. NEW COMMON|5.01
20140114|630087203|NNVC| 98|NANOVIRICIDES, INC. NEW COMMON|5.08
2nd Half Jan 2014
20140115|630087203|NNVC| 1262|NANOVIRICIDES, INC. NEW COMMON|5.39
20140116|630087203|NNVC| 994|NANOVIRICIDES, INC. NEW COMMON|5.39
20140117|630087203|NNVC| 10264|NANOVIRICIDES, INC. NEW COMMON|5.79
20140121|630087203|NNVC| 5082|NANOVIRICIDES, INC. NEW COMMON|6.05
20140123|630087203|NNVC| 18335|NANOVIRICIDES, INC. NEW COMMON|4.84
20140124|630087203|NNVC|882616|NANOVIRICIDES, INC. NEW COMMON|4.85
20140127|630087203|NNVC| 47085|NANOVIRICIDES, INC. NEW COMMON|4.80
20140128|630087203|NNVC| 7227|NANOVIRICIDES, INC. NEW COMMON|4.85
20140129|630087203|NNVC| 5043|NANOVIRICIDES, INC. NEW COMMON|4.83
20140130|630087203|NNVC| 1592|NANOVIRICIDES, INC. NEW COMMON|4.57
20140131|630087203|NNVC| 2260|NANOVIRICIDES, INC. NEW COMMON|4.75
1st Half Feb 2014
2014 02 03 -27 |630087203|NNVC| 1680 |NANOVIRICIDES, INC. NEW COMMON| 4.58
2014 02 04 -28 |630087203|NNVC| 1674 |NANOVIRICIDES, INC. NEW COMMON| 4.42
2014 02 05 -31 |630087203|NNVC| 1305 |NANOVIRICIDES, INC. NEW COMMON| 4.65
2014 02 06 -03 |630087203|NNVC| 300 |NANOVIRICIDES, INC. NEW COMMON| 4.60
2014 02 07 -04 |630087203|NNVC| 2084 |NANOVIRICIDES, INC. NEW COMMON| 4.47
2014 02 10 -05 |630087203|NNVC| 1662 |NANOVIRICIDES, INC. NEW COMMON| 4.43
2014 02 11 -06 |630087203|NNVC| 4289 |NANOVIRICIDES, INC. NEW COMMON| 4.42
2014 02 12 -07 |630087203|NNVC| 5660 |NANOVIRICIDES, INC. NEW COMMON| 3.36
2014 02 13 -10 |630087203|NNVC| 8018 |NANOVIRICIDES, INC. NEW COMMON| 3.48
2014 02 14 -11 |630087203|NNVC| 793 |NANOVIRICIDES, INC. NEW COMMON| 3.11
2nd Half Feb 2014
17 -12 0*
2014 02 18 -13 |630087203|NNVC| 272 |NANOVIRICIDES, INC. NEW COMMON| 3.45
19 -14 0
2014 02 20 -17 |630087203|NNVC| 6989 |NANOVIRICIDES, INC. NEW COMMON| 4.00
21 -18 0
2014 02 24 -19 |630087203|NNVC| 5899 |NANOVIRICIDES, INC. NEW COMMON| 3.87
2014 02 25 -20 |630087203|NNVC| 6310 |NANOVIRICIDES, INC. NEW COMMON| 3.89
2014 02 26 -21 |630087203|NNVC| 811 |NANOVIRICIDES, INC. NEW COMMON| 3.99
27 -24 0
2014 02 28 -25 |630087203|NNVC| 29862 |NANOVIRICIDES, INC. NEW COMMON| 3.90
1st Half Mar 2014
2014 03 03 -26 |630087203|NNVC| 4834 |NANOVIRICIDES, INC. NEW COMMON| 3.98
2014 03 04 -27 |630087203|NNVC| 186 |NANOVIRICIDES, INC. NEW COMMON| 4.04
2014 03 05 -28 |630087203|NNVC| 245 |NANOVIRICIDES, INC. NEW COMMON| 3.96
06 -03 0
2014 03 07 -04 |630087203|NNVC| 172 |NANOVIRICIDES, INC. NEW COMMON| 3.79
2014 03 10 -05 |630087203|NNVC| 380 |NANOVIRICIDES, INC. NEW COMMON| 3.77
2014 03 11 -06 |630087203|NNVC| 11974 |NANOVIRICIDES, INC. NEW COMMON| 3.81
2014 03 12 -07 |630087203|NNVC| 28213 |NANOVIRICIDES, INC. NEW COMMON| 3.86
2014 03 13 -10 |630087203|NNVC| 12910 |NANOVIRICIDES, INC. NEW COMMON| 3.89
NOTE: SEC does not report days with 0 FTD. I have added the "0" days here to more clearly indicate the spike in FTD shares on Feb 28 (29,862) vs the days around it which killed the fill-the-gap rally in the shares that was well on its way after the PT libel article.
Should be nice to see what comes from EU, but Tox is what matters most - as that is the critical path on the timeline.
I should cover for myself on one point. I said NNVC missed their stretch goal to start the Regulatory GLP Toxicity Study at BASi by Q1 2014.
However unlikely, it is possible they started it by March 31 and have not yet PR'd it.
This was what they did when they released on Oct. 7, 2013 the PR for the Range Finding Toxicity Study which started in late September 2013.
If so, a PR might not happen until Dr. Seymour's return.
Although possible, I'd give this possibility very, very low odds of happening based on impression I got from the shareholder letter.
Sorry I wish that was started and PR'd - but no info yet.
The BASI study is the second part of formal toxicity. That was point 2 in my post - Regulatory GLP Toxicity Study which will be done as you say at BASI.
Per the shareholder letter of March 11, "We expect the scale up of injectable FluCide in our current facility to be completed in 2014. We would then have sufficient material to begin the FluCide “Tox Package” studies, and expect to initiate the same. "
I have not seen further press releases since March 11.
Industry, at least in my experience, doesn't use "GLP materials" terminology - just to note this.
Although "GMP materials" or "cGMP materials" are often used in industry, GLP terminology is used to describe laboratory studies. Materials used for those studies could come from anywhere, as long as they are adequately characterized to inform the study design to produce meaningful results and conclusions.
So it would be better to say "materials for GLP" than "GLP materials."
Agreed, Lief, the Reg Tox start committed to in the shareholder letter is 2014. This is surely sandbagged. Their stretch goal was Q1 2014. They have missed that. There is no way they will miss the 2014 commitment to start Regulatory Toxicity testing, IMHO.
I have been targeting a Q2 2014 Regulatory Toxicity Study start. I do not have any documentation to support that and do not have any of the inside info that would help better inform that call. It is just my gut feel based on my observations managing similar projects.
Cheers!
Tox studies have started and other misinformation corrections (thanks, Leif).
I don't have a lot of time to post, but sometimes it is just hard not to correct all this. I think my posts would get more reading if I was able to post during the day, but I only usually have time at night.
1. Formal Tox Studies have started and the Range Finding Toxicity study is complete with NO SIGNS of toxicity (NONE).
2. Regulatory (GLP) Toxicity study materials DO NOT require cGMP manufacturing but need characterization per GLP.
3, Material for Regulatory GLP Toxicity studies will be produced in the existing NNVC plant.
4. Scale up is NOT required by FDA for Toxicity studies. HOWEVER, NNVC will LIKELY NOT start Regulatory GLP Tox until scale up is complete in the existing facilities to reduce risk to scale up of clinical and commercial production.
5. Regulatory GLP Tox Studies and cGMP qualification will be concurrent so Tox cannot require cGMP.
6. Also N.B. - Clinical Trials in Australia and other locations require only "cGMP-like" drug product - accelerating timelines once Tox is complete.
These points are supported below:
1. Formal Tox Studies have started and the Range Finding Toxicity study is complete with NO (NONE) signs of toxicity in a rigorous study required as per industry standards following Good Development Practices (GDP) documented as part of the NNVC Quality System
Point 1 is covered in my previous post LINK: Post 85041.
2. Regulatory (GLP) Toxicity studies (2nd part of "formal" Tox and included as part of a larger "Tox Package" required for IND/CTx/etc. submissions) DO NOT require cGMP manufactured materials (right, thanks Leif for setting that straight). They are required to meet GLP requirements. GLP essentially ensures the study is well designed and documented e.g. - test materials are fully characterized with batch release results, concurrent stability testing and other characterization - without additional cGMP requirements on the details of the materials' manufacturing, controls, process validations, etc. Characterization for GLP is "WHAT" test materials not necessarily "HOW" test materials are made.
3, Material for Regulatory GLP Toxicity studies will be produced in the existing NNVC plant.
Points 2 and 3 are clearly covered in the March 11 Shareholder letter: "We intend to make the drug substance for the tox package study in our current R&D facilities. The tox package study does not require a cGMP product."
4. Scale up is NOT required by FDA for Toxicity studies. Bridging studies are commonly used in studies to show equivalence of batches produced at different manufacturing scales. Scale up was not used for the Range Finding Toxicity Study and is not required for the Regulatory GLP Toxicity Study. (BigKahuna is right).
HOWEVER, there is risk to the CMC requirements for consistency of each level of scale up from what is tested in Regulatory GLP Tox to the Clinical Trials and subsequent commercial production. My opinion is that although they could, NNVC will LIKELY NOT start Regulatory GLP Tox until scale up is complete in the existing facilities (Rawnoc is probably right on this point but if wrong, it is a wildcard to a near term upside).
My opinion on Point 4 is based on the Shareholder letter: "We expect the scale up of injectable FluCide in our current facility to be completed in 2014. We would then have sufficient material to begin the FluCide “Tox Package” studies, and expect to initiate the same."
5. The last confirmation that cGMP qualification and the Regulatory GLP Tox Studies will be concurrent also comes from the Shareholder letter: "We anticipate the tox package report on FluCide about 6 to 9 months after commissioning the study. We are hoping to have c-GMP compliant FluCide production batches completed at around the same time."
6. Also N.B. - Clinical Trials in Australia and other locations require only "cGMP-like" drug product with validated manufacturing and documentation to show they meet human use requirements without full FDA cGMP certification and will occur more quickly than cGMP per FDA requirements.
DISCLAIMER: I am long NNVC but have put in stink bids at lower prices should the SP continue to drop. I may benefit either way the SP goes in the short term. I will only profit if SP goes up in the long term.
I don't know and have to run again. Maybe someone else can answer your question.
Again twisted logic
Rawnoc - "Not a sign of support"
In reply to...
L Vus - "Dr. Eva Harris said it was important that this science be approved"
I don't know the exact answer to that. However, it seems to me to be in the best interests of NNVC to take on the responsibility with TC support.
In addition to FluCide cGMP requirements, NNVC will dictate the timeframes and number of R&D projects that will also be conducted in separate suites of the new facilities. That wouldn't be something TC could or should do. But I am sure that TC would have to have been called in to provide the technical details on the number of unit operations, the size of the vats, the hookups required for the process parameters, any additional environmental control requirements, etc.
The use of EbolaCide is blocked by FDA regulations and developmental timelines.
Bloomvest: "Guinea battles to contain Ebola as Senegal closes its border
Why isnt the government knocking on NNVC doors if the cides are so effective? Why?"
My understanding is that NNVC would require FDA approval to sell not only in the US (after IND and NDA approval) but also outside the US (with lesser requirements).
Any manufacturing for sale and use outside the US requires notification of the FDA. I do not know exactly what all of those requirements are, but one of them is that if it is a pharma product that it must have at least gone through Regulatory (GLP) Toxicity testing before use and sale.
This is the same requirement FDA has for use of drug product in Clinical Trials outside the U.S.
Having said that, the tragedy in Africa with Ebola is frustrating for all of us who believe nanoviricides would help save lives if it was further along in development.
All the more reason for NNVC to be aggressive with timelines to Tox and clinical trials for FluCide so they can save lives being lost to Flu and develop other products to save lives.
LoanRanger - I don't think they are.
LoanRanger: "Perhaps this question is too simplistic, but why is NNVC engaged in activities (manufacturing and development) that they compensate Theracour to perform?"
NNVC contracts with TC to do manufacturing and development. NNVC does not directly employ anyone to do those activities. Unless I am missing something?
Crossbone - I am still long as well and will be buying again if the price goes low enough - like DrKaz.
Between work, family, funerals, kids' activities, it is getting harder to post. But there are still many out here who won't sell unless something factual AND TRUTHFUL (NOT Colbert-type twisted "truthiness") comes out to change our investment hypotheses in the company.
Timelines are slower than I like, but the rest is holding up IMHO.
Cheers!
18mo from preIND to formal Range Finding Tox which is complete and successful with no toxic effects for a dose ~100x the efficacious dose used to save 100% of mice from a lethal dose of Flu that killed 100% of mice not treated.
The claim about Tox not starting ignores these multiple doses tested up to the Max Feasible Dose (100x therapeutic dose) in extensive testing in mice with hard histology, blood draws, autopsies, end organ inspections and behavioral observations for endpoints of Toxicity in the RF Tox study - which is an industry standard for Toxicity testing - as indicated in a previous post of mine this month.
Since RF Tox in September, ~6mo have passed. I did think their scale up would go quicker, but the batches manufactured for scale up will be used for Regulatory GLP Tox and without further delay.
The batches for Reg GLP Tox at BASI are being scaled up at the existing plant.
THESE BATCHES ARE NOT cGMP or cGMP-like and so do not need commissioning.
Identical equipment and processes will be used in the new production facility to minimize changes for the move.
It is unclear whether they will take a conservative route (too conservative in my strong opinion) and wait until the new facilities, equipment and processes are complete and repeat batches to confirm they match the batches being used for the Reg GLP Tox. This would be an unnecessary delay in my opinion because bridging studies are done all the time. But even if they did wait, these batches are not required to be cGMP. This is an R&D test that confirms for the company that they will not be wasting money and time by testing Reg GLP Tox with materials that are not consistent with new materials to be made in the new facility. Because of this, the R&D confirmation studies could go much faster than a full cGMP commissioning.
Won't be able to answer more today as I am late for real work.
TASKS resulting in RangeFinding Toxicity 18mo after preIND meeting
There are good reasons for conservative timelines to start the formal Range Finding Toxicity study after the pre-IND meeting.
The design of the drug may have been optimized and finalized at the time of the pre-IND, but the consistency of the manufactured materials with the various processes would not have been.
The 3 scales of manufacturing processes below need to have similar CMC with respect to specifications and characterization of the product output.
1. Lab scale for formal Range Finding Toxicity Study
2. Larger lab scale for GLP Regulatory Toxicity study, PK and PD studies
3. Commercial scale to manufacture cGMP product for human clinical studies.
All potential specifications and characterizations of the test materials need to be consistent across each of the 3 scales of processes to assure the early tests can be leveraged for the later ones with sound scientific basis that can be used to support CMC and regulatory submissions as a total package.
Some potential specs might include Dose, Manufacturing Impurities, Degradant levels at batch release, PEG average molecular weight/number and PDI, overall molecular weight and range, ratio of PEG to fatty acid bridges, number of ligands per 'cide and characterizations might include degradation time in vitro, morphological state in solution, etc. There are average values and variation for each of these that must be controlled and shown as consistent across all of the processes to justify leveraging.
Therefore, they needed to make sure they could reliably make consistent product across all processes before starting the first tests to not waste money or time on a false start.
Other tasks resulting in an 18 month timeline from pre-IND to initial Tox testing:
1. My speculation is that it wasn't until the pre-IND meeting that they really knew everything the FDA wanted to see for CMC and characterization. As they said after the pre-IND in March 2012, FDA gave them specific recommendations for FluCide not included in the standard FDA Guidance documents. FDA likely asked for specific assays and tests and testing plans that needed to be developed, validated and executed. And then multiple lots would have had to be made and tested to set representative specs and tolerances.
2. Annual Report (excerpt below) states they intended to build all Tox study materials at the larger-scale new facility, but schedule and resource constraints there forced them to scale up and make in the smaller-scale laboratory facility. And then they didn't have all the equipment. My opinion - by not realizing sooner the new facility wouldn't be done in time, they cost themselves some time to do the lab scale up in existing facilities. But to their credit, they did recover and find a way to get an important portion of the formal Tox studies started (barely) by end of the wide range of their self-imposed deadline.
3. Multiple process optimizations followed by builds to establish reproducibility, capability to specs and consistency in characterizations all take time as well to make sure batches made now for non-GLP are consistent with batches to be made for GLP animal and Human Clinical studies.
Excerpts:
Press Release Oct 7, 2013
The non-GLP safety and toxicology study was begun in late September at KARD Scientific in Massachusetts. The results of this study will provide the basis and focus for the IND-enabling GLP safety and toxicology studies of FluCide that are required for the IND submission to the U.S. FDA.
Annual Report June/Sept 2013
After declaring the injectable FluCide drug candidate in February 2012, we have been focused on taking our technology from the small scale syntheses needed for small animal studies to the large scale syntheses for making large batches of our nanoviricides as would be needed for Safety and Toxicology (“Tox Package” studies) and later for human clinical trials. Because of the significant safety observed during the several animal studies designed to test the effectiveness of FluCide drug candidates in small animals, the scale required for the tox package studies was estimated at kilograms. Originally we had intended to perform kg-scale syntheses only after the new lab and facilities designed for such scale up was available. However, the facility program was significantly behind due to challenges related to resources availability as well as significant challenges posed by the need for designing complex functionality in a limited space while performing renovation of an existing space. We therefore decided to perform the synthesis of FluCide for tox package in our existing small-scale laboratory. We have been optimizing the processes and translating laboratory operations to appropriate chemical process unit operations in the subsequent time frame. This is a very significant undertaking, given the constraints of our current small-scale facility. After we have completed these process optimizations, we will still need to produce at least three to five batches of the injectable FluCide, analyze the product for comparability, and combine these batches to produce a master batch sufficient to perform the tox package studies with. These activities are currently in progress.
While we have made significant progress in this scale up program at our current facility, certain key equipment pieces that we need are still on back order at present with certain vendors. After these equipment pieces arrive, we will need to set them up, validate them and then use them for the operations they are intended for. This continues to be an item causing delays in our goal of making sufficient quantities of FluCide for the tox package study and it is outside of the Company’s control.
Nick - Thanks for taking the time to put some data behind my general statement.
The Bolinger Bands are tightening and looking for a breakout.
Technically this could be either direction.
Fundamentally, I'm thinking it fills the gap on its way up due increasing institutional interest and *hopefully* a near future milestone announcement from the company.
Cheers!
Nicely stated, Steady T and a reasonable approach. I am long NNVC, although I am also concerned that they have been too conservative and that has hurt their timelines. I am also ready to pull out my investment if I see what I judge to be real issues with the company or technology.
I understand your putting importance on the FDA related milestones. The Range Finding Toxicity testing done was good (no toxic effects), but NNVC needs the larger, more rigorous GLP Regulatory Toxicity Study done in order to file an IND with the FDA. And they also need more Efficacy testing done on other Flu strains in order to apply for broad spectrum indication for FluCide.
The timeline committed to in the CEO letter to start the GLP Reg Tox is 2014, but the stretch goal is to start clinical studies as early as the end of 2014 or Q1 2015. My own guess is that this Tox study will be started by June 2014 and the clinical trials in Australia will start by Q1 2015.
I would suggest that in addition to FDA milestones, you may want to consider the potential earlier start to clinical trials by submitting a CTx filing in Australia where the company has said it may start CTs. This could happen sooner than the FDA IND submission.
Another consideration is that the company will likely file their IND with a request for Breakthrough Therapy or another accelerated Reg filing. If granted, they will be able to work with FDA in a real time review setting which may help them get through more quickly any concerns the FDA may have with their manufacturing consistency and scale up. I DO NOT think this will be any help in the short term but may help after they file the IND.
Good luck to you.
Share price has been steadily recovering.
The first amendment, claims about no progress (rather than the actual conservatively slow progress), etc, etc, etc.
None of them matter. What matters is continued progress toward commercialization. 2014 is set up with the company to start knocking off the milestones one by one.
Short at your own risk.
My 15yrs in medical industry says timeline's met. I will admit that I am more of a generalist and I have to dig into some of the details, but my DD (below) combined with my discussions with DVMs have convinced me of this.
I will grant that the following communication from Dr. Seymour could have been more clear for lay people.
We are doing all of the preparatory pre-tox work now and the formal tox studies by BASI will start as soon as the pre-tox work is done and an sufficient amount of material is available from the existing lab
We're estimating a June start though that could go either way by 2-3 months depending on both BASI's schedule and ours.
RAWNOC POST: Name a single deadline NNVC met in 9 years. Name just one. If anybody can do that, then I might agree there is a snowball's chance in hell that they will get Tox done this year.
6 Dose Range Finding Studies (DRF)
The primary objective of a DRF study is to establish a dose response and provide the data to enable appropriate dose selection for subsequent regulatory toxicology studies. Generally, DRF studies are initially carried out in rodents, progressing to non-rodents when the adverse effects in rodents are understood. Guidance on industry recommendations for MTD/DRF study design in dogs has been published elsewhere (16). The DRF studies are not normally classed as regulatory studies and provide essential information on:
>Doses for subsequent regulatory studies
>Adverse effects associated with the test item and dose, which can be used to devise a strategy to
reduce the adverse effects in longer term studies, for example, application of humane endpoints
>Intrinsic hazards associated with the test item. This may be used to identify test items not suitable for future development thus avoiding subsequent animal use
7 Regulatory Toxicology Studies [Performed under GLP - Good Laboratory Practices]
Regulatory toxicology studies of up to one month in duration to support Phase I clinical studies are informed by, and follow on from, the initial short term DRF studies. The following section provides a framework for selecting doses for regulatory general toxicology studies.
NNVC has not missed a communicated deadline in the last year. Do you not read others' posts?
LINK:84922
Considering the paucity of information in previous posts, I hope at least a modicum of homework is done to support the claims - if there is any truthful support to be found.
It's the weekend. I'm done with this sewage until my report release early next week. (Oh boy...)
Yes. They didn't need scale up for the Range Finding Tox studies and it is NOT a hard requirement for Regulatory (GLP) Tox studies.
The company is being conservative with respect to making preclinical (animal study) and clinical batches within one level of the scale up they anticipate they will use for production of their commercial product. Right now, for the Range Finding Tox, they are 2 levels of scale up from their anticipated commercial manufacture.
RAWNOC POST: NNVC hasn't completed scale up production model at the existing facility. How can they produce sufficient quantities for Tox until this is completed? How can Tox start in May if they haven't figured out how to make enough of the 'cides, let alone begun actual production of the 'cides for tox?
Leifsmith - That was my own (Robi-1) speculative timeline based on the information available. Dr. Seymour has set more aggressive "goals" but has set less aggressive "commitments" in his letter to shareholders. My (Robi-1) speculation falls between the two, below:
My speculative timeline is
1. Start of Tox before June 2014 (maybe much earlier for a positive surprise)
2. Completion of Tox and efficacy studies before Dec 2014
3. Submission of Australia regulatory paperwork in Jan 2015
4. Start of Clinical Studies by Feb 2015
RAWNOC POST: Name a single deadline NNVC met in 9 years. Name just one. If anybody can do that, then I might agree there is a snowball's chance in hell that they will get Tox done this year.
6 Dose Range Finding Studies (DRF)
The primary objective of a DRF study is to establish a dose response and provide the data to enable appropriate dose selection for subsequent regulatory toxicology studies. Generally, DRF studies are initially carried out in rodents, progressing to non-rodents when the adverse effects in rodents are understood. Guidance on industry recommendations for MTD/DRF study design in dogs has been published elsewhere (16). The DRF studies are not normally classed as regulatory studies and provide essential information on:
>Doses for subsequent regulatory studies
>Adverse effects associated with the test item and dose, which can be used to devise a strategy to
reduce the adverse effects in longer term studies, for example, application of humane endpoints
>Intrinsic hazards associated with the test item. This may be used to identify test items not suitable for future development thus avoiding subsequent animal use
7 Regulatory Toxicology Studies [Performed under GLP - Good Laboratory Practices]
Regulatory toxicology studies of up to one month in duration to support Phase I clinical studies are informed by, and follow on from, the initial short term DRF studies. The following section provides a framework for selecting doses for regulatory general toxicology studies.
Thanks for the link, Doc. Looks interesting - some light reading for the weekend. Cheers!
I should add that the residence time of will depend on the molecular weight of the oral FluCide. I think from previous posts that oral FluCide is anticipated to have a residence time of 60-90 days. But the concentration will decrease over time, so it is unclear what the re-dosing timing should be - if it is needed at all.
I really don't know, but my guess is that the SP will be about double the price at the beginning of the year (~$5) when they file the IND (FDA) and/or CTx (Australia) - ~$10.
$8 would be great, too!
We'll see...
You make a good point, AV-2. Almost all would not be taking oral FluCide long-term. However I was thinking of the low-likelihood scenario of a longer-term epidemic of a breakout Flu strain with no vaccine where healthcare workers might need to take multiple doses of FluCide prophylactically.
So even though really unlikely, I would think NNVC would probably do long-term multiple doses for Toxicity testing of Oral FluCide. I could be wrong.
To FamilyMan's point, there would likely be other 'Cides that would be taken long-term. And already having long-term multiple use Tox data on one product could theoretically reduce the amount of long-term testing needed for the next 'Cide.
Note: Testing for continuous long-term use is not likely to be included in injectable FluCide Toxicity Study as that is meant to be a one-time (or maybe at most 2-time) injection for hospitalized Flu patients.
However, oral FluCide is planned for prophylactic use and multiple, long-term dosing will need to be investigated in a follow-up Toxicity study for that dosage form.
I agree Dr. Hari - my main worry is also that it takes NNVC too long to get into the clinic.
The balance is speed vs. going through all the paces the FDA and other WW reg bodies require.
I know of instances where specs were held more tightly than needed for safety and efficacy and that leading to poor process capability and consistency and repeatability in processing batches.
But CDER in FDA seems to be on the warpath of "consistency" and can greatly slow or stop you in your tracks if you don't meet their expectations - sometimes arbitrary and unrealistic expectations without consideration for practical, common sense balance of good enough for safety and efficacy vs. their (CDER) idea of perfect from a consistency standpoint.
So they are walking a fine line here. It appears that they feel they need to wait for scale up to make the Tox batches and processing more consistent with the planned further scaled up processing of batches they will make for clinical and commercial use.
There are a lot of judgement calls here and NNVC seems to be operating very conservatively. I hope not too conservatively.