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Interesting bifurcated NNVC risk/opportunity as soon as Monday.
I've been doing a little more research into PEG toxicity, ICH guidelines for Tox testing, etc.
We have great results for FluCide from clinical observations of the mice in the intial Tox study.
But we are still waiting on autopsy, histology, blood test and other results from the study.
We could get these results as early as Monday (seems to be the day they like to release these PRs) - or maybe one of the 2 Mondays following.
1. If the remaining results of this worst case MFD (Max Feasible Dose) Tox come out with some limited toxicities - that could still be okay and not reduce the long-term promise of the technology - but it would make the stock price drop near-term.
2. If the remaining Tox results for this are clean - IT IS OFF TO THE RACES. The remaining GLP Tox for the IND will NOT include higher doses than used for this non-GLP Tox Study (per ICH M3(R2)) AND will take 2 WEEKS OR LESS for each dosing/animal regimen tested. Even in series, these IND GLP TOX TESTS WILL BE COMPLETED RAPIDLY (much faster than I thought initially). The only remaining hold-up would be manufacturing the material for the study - which is taking place NOW.
See below for more info. As for me, I am now even more optimistic about more very near-term catalysts and have added to my holdings.
Interesting finding #1
http://dmd.aspetjournals.org/content/35/1/9.full.pdf" rel="nofollow" target="_blank" >http://dmd.aspetjournals.org/content/35/1/9.full.pdf[tag]PEGylated Proteins: Evaluation of Their Safety in the Absence of Definitive Metabolism Studies
Rob Webster, Eric Didier, Philip Harris, Ned Siegel, Jeanne Stadler, Lorraine Tilbury, and Dennis Smith[/tag]
The source above is great reading for the scientists here. This is a "mini-review" on Toxicity of PEG and expected Tox of PEGylated proteins (chemically very similar to the FluCide micelles with PEG and protein/peptide (like FluCide PEG & ligands) but do not have the pendant fatty acid linkages of FluCide). The review talks about various routes of metabolism/elimination of PEG. For the most part, PEG of molecular weights most likely used in FluCide is principally removed gradually from the blood through glomerular filtration in the kidneys and excreted in urine (although small amounts may also be eliminated through metabolism and the liver/bile/fecal path). These elimination pathways identified a risk I don't believe has been covered before on this message board. At VERY, VERY high levels of intravenous injection or oral dosing of ~2-4g/kg/day, there is a possibility of kidney, liver or other non-outwardly observable toxicities due to overwhelming the biological processes of elimination in those end organs.
Possibility - There is a very small possibility that the high levels in the Max Feasible Dose FluCide Tox study will reveal histological toxicities not apparent from clinical observations (but see below).
Interesting Finding #2
FDA/ICH M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals
M3(R2) EMA Q&A
LASA Guide on Dose Level Selection for Reg Tox Studies - Great overview and perhaps most accessible to lay person. Emphasis on humane, minimal use of animals (Weedie should appreciate that part!)
There are 4 options for Selecting the Highest Dose for Tox studies according to ICH M3(R2):
Max Feasible Dose (MFD), Max Tolerated Dose (MTD), Exposure Saturation and Mean Exposure Margin 50x Clinical. ANY of these options are EQUALLY acceptable for the High Dose Selection for Tox studies. The preliminary Tox study was MFD and consisted of a 1 hour infusion of concentrated dose of FluCide. With the estimated expected dose required for human use to be about 1.3g in 15cc of saline (my interpretation of Big K's previous post), this would be 1.3g/70kg one time dose or 0.02g/kg/day. Multiply this by a safety factor of maybe 20 times and a (very speculative) MFD may be say a 0.4g/kg/one-time dose they may have used in this Tox study. To make sure they wouldn't overwhelm the circulatory system and waste-processing organs with a bolus of drug all at once, an infusion over 1 hour was used to spread it out. So my own very speculative calculation of the worst case dose that may have been used in the preliminary FluCide Tox study (~0.4g/kg/one-time) is about an order of magnitude less than the levels of dosing that produced toxic effects in the reference above (~2-4g/kg/day) over a period of many days.
One final IMPORTANT TIMING note - In looking through ICH M3(R2), THE REQUIREMENT FOR DURATION OF TOX TESTING IS JUST 2 WEEKS OR LESS for single use pharmaceuticals (equal to duration of use in clinical studies). That means these GLP TOX TESTS WILL BE COMPLETED VERY QUICKLY - FURTHER ACCELERATING THE PATH TO FIRST HUMAN CLINICAL USE.
Echo - Ok if I take a stab at this?
If I understand your question, I think the answer is 'No". This one-time process development work will not increase the time to make FluCide for ongoing Clinical and Commercial purposes.
The decision to make Tox package materials in the existing lab facilities added time to obtain equipment, process optimization, etc. --- BUT THIS WILL NOT AFFECT the time to make human Clinical or Commercial FluCide, since they will NOT be made in the existing lab facilities.
The decision to make Clinical and Commercial materials in the new cGMP facility was made long ago. There were delays (according to the Annual Report) in designing the layout to accommodate multiple unit operations for multiple independent manufacturing lines (important for cGMP). And other delays for equipment. And it will still need to go through qualifications, process optimization, validations, etc.
---But once this initial process development work is done, it will not need to be done again.
---Once set up, this will not affect the ongoing processing times or the ability to make clinical or commercial product.
I've been thinking about this, and there is only one way I can think of that this makes sense.
It only makes sense (to me at least) as just a 1.3 gram dose that is suspended in a total of 15cc of saline.
My reasoning is that a full tablespoon (15cc) of dry volume would be a very large embolic load directly into the bloodstream in a typical short duration injection. So that doesn't seem right.
If that is the case, the other numbers only confuse the calculations (not that I don't appreciate them - it always helps to have more information for general understanding).
I actually tried some calculations first, but they didn't make sense.
But somewhat informative - I looked up the specific gravity of PEG (denser than water) and fatty acids (less dense than water) and at ~50/50 ratio the overall specific gravity would be just above 1 g/cc.
So if my suspicion is right and the dose is 1.3g, that would just over 1.3cc which is a much more reasonable embolic load in a typical IV injection of ~ 15cc.
If so, there would be 769 doses in a 1kg batch (1000g/1.3g).
From Big K's dose estimate of 1.3g/15cc, I am assuming this means 1.3g of FluCide suspended in ~1 TBSP or ~15cc of (saline?).
1 dose/1TBSP x TBSP/15cc x 15cc/1.3g x 1000g/batch = ~769 doses/batch
or simply 1000g batch divided by 1.3g per dose = ~769 doses per KG-size batch
The math is right, but the answer is only correct if I made the correct assumptions up front. Are they?
By the way, where does this dosing come from? And wouldn't the dose amounts or number of doses need to be varied in the Tox studies?
Info relating to Shelf Life/ Storage Conditions
Interesting question from technical/regulatory standpoint, but shelf life and storage conditions are not likely to be very impactful to the overall value of the technology if it works as well as expected.
There is a lot to this question, so I will give quick answers up front and more details below.
1. NNVC can estimate shelf life (including how long the drug product will last without degradation). They will have a good idea based on the chemistry of the linking functional groups and have almost certainly done preliminary stability testing. But it looks like linking chemistry is proprietary - so we ourselves can't really guess. GLP Tox will be the first required formal stability study - likely concurrent with the Tox testing. Jain BioPharma report does say stable at room temperature, though.
2. FluCide will not likely require refrigeration (based on the chemistry and the Jain BioPharma report, below, which I am sure NNVC contributed to).
TECHNICAL
[Note: I am not a chemist, but have some chemistry background to try to expand upon what I can find from public information...]
From public information, we know that FluCide micelle is a polymer chain made up of PEG (hydrophilic) backbone, fatty acids (hydrophobic), and sialic acid mimics (ligands) [Top of p. 12 Annual Report]
What I couldn't find is the functional chemistry(s) linking these constituents together (patent literature is broad and not specific to final FluCide design that I could see).
The undisclosed linking chemistry is key. Some chemical bonds are more susceptible to degradation. Also, total molecular weights of the constituents can influence degradation.
- FluCide is likely to be relatively more biodegradable for faster elimination from the body (no specific reference I could find, but a hint may be found in the dosing regimens in mice studies of every other day p. 32-35 Annual Report).
- The HIVCides are likely to be relatively less biodegradable to have a more sustained therapeutic effect (p. 38 Annual Report).
NOTE: WE SHOULD KEEP IN MIND THAT EVEN BIODEGRADABLE MATERIALS CAN BE PACKAGED/STORED IN WAYS THAT PREVENT/HINDER DEGRADATION AND HAVE LONG SHELF LIFE.
More info in Jain BioPharma market report...
There was a excerpt on the nanoviricides chapter in the Jain BioPharma market report on the Technology webpage of Nanoviricides.com. The link says this is from Jan. 2008, so it may or may not apply to the final FluCide selected as the clinical candidate in Sept 2011.
Nanoviricides are safe because of their unique design and the fact that they are designed to be biodegradable within the body.
Advantages of Nanoviricides over immunoglobulin therapies are:
1. Fully chemical, room-temperature stable NanoViricides can be made against many diseases
Justification for ~18mo timing from pre-IND to Tox was covered previously.
For those who missed it... a bit long because of follow-up questions, but (I think) worth the read.
Post 75148 from r-1-k
NT there are good reasons for waiting to start the non-GLP Tox range finding.
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 manufacturing processes need to have similar CMC with respect to specifications and characterization of the product output.
1. Lab scale for non-GLP Tox range finding
2. Larger lab scale for GLP Tox testing, 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 processes to assure the early tests can be leveraged for the later ones with sound scientific basis that can be used to support 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.
Thank you for the explanation. Can #2 and #3 be done without the facility available?
Still not clear on why this would take 18 months.
No, only non-GLP and GLP Tox Pkg animal studies (#1 and #2) are planned to be done in the existing facility. The human clinicals (#3) will be done in the new facility, which must be cGMP for US trials or cGMP-like (same practices but without FDA designation) for OUS trials, as in Australia which the company seems to have chosen for their FIM (First in Man) trial (old industry term holdover though not politically correct).
While it might be theoretically possible for them to manufacture cGMP-like materials for clinicals in the smaller lab, they have consistently stated in PRs that they plan to make these in the new facility. There may be constraints in the existing labs that prevent or make costly achieving cGMP.
NOTE: I have made an assumption that #1 (non-GLP) are different lots on different scale than #2 (GLP) based on the Annual Report that stated they were still waiting on equipment for the 3-5 batches needed for a large enough composite to complete their Tox Package. It is possible, though I think unlikely, that the statement in the September-30-released Annual Report applied to the June fiscal year end and that in the few months after June 30 they got the equipment, made the batches, completed batch release and characterization testing, blended and batch released the composite batch, and started the studies using one master batch intended for both #1 non-GLP and #2 GLP. As I said possible ... but not as likely.
As for why it took 18 months from pre-IND to initial Tox testing, there are/could be several reasons.
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 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.
Thank you, I appreciate your explanation, but I was asking about #2 and #3 being done with existing material because you said that that was part of the reasoning behind the delay was "the consistency of the manufactured materials with the various processes would not have been optimized and finalized." Combining that with the theory that they needed to work out the scale up formulations, I am still not clear as to why they would have to wait 18 months.
If as you claim, they were originally planning on doing tox (preliminary or GLP) with materials from new plant, then they could have NEVER been started in '13, which certainly was a claim made by the company.
I am glad that they realized this was an impossibility, regardless of when equipment was delivered, and have announced a new course of action.
I find many of the posts here similar to many of the NNVC releases. Little focus on the topic or subject, and then a whole lot of space used to explain tangential and unrelated or unasked issues.
I am not referencing your post.
Regarding the 18 month delay. I do not accept your theory.
Point #1 is not actually stating anything except when the 18 months began.
Point #2 might explain why they waited 12 months to start, but per my point above, is inconsistent with them EVER being able to start in '13 as the facility was not EVER planned on being operationally sound until late'13 at the earliest.
Point #3 is not relevant to why they started preliminary tox 18 months after their FDA meeting.
For me, that is still the question.
Thank you for your response.
Timelines - I address each point in red, Nanotoday.
I was asking about #2 and #3 being done with existing material because you said that that was part of the reasoning behind the delay was "the consistency of the manufactured materials with the various processes would not have been optimized and finalized." Combining that with the theory that they needed to work out the scale up formulations, I am still not clear as to why they would have to wait 18 months.
- I am not sure what you mean here. #1 was lots for non-GLP, #2 was lots for GLP, #3 was cGMP/like lots for Clinical. #3 could never be done with existing materials. Perhaps (not sure) you mistook my statement on "consistency of manufactured materials" to mean all materials have been made? That is not the case, because I stated they still likely need to make lots for GLP and certainly have to make cGMP/like materials for clinicals. If I wasn't clear, I meant that there would need to be confidence that practice runs for the individual unit operations of the larger scale operations were reproducible with manufacturing capability to specs and tolerances and consistent in characterization tests across each of the 3 processes (manufacturing for the non-GLP, GLP and Clinical purposes).
If as you claim, they were originally planning on doing tox (preliminary or GLP) with materials from new plant, then they could have NEVER been started in '13, which certainly was a claim made by the company.
- Not as I claim, but as the 2013 Annual Report claims. But you are right that this seems inconsistent. The early PRs do speak to non-GLP testing, but not specifically as to what the timelines were for non-GLP and GLP. I wish the company was more clear on timelines and specifics as well.
Regarding the 18 month delay. I do not accept your theory.
- I would not call it theory. Rather, it is based on public records and educated assumptions based on analogous industry observations. I admit to my assumptions as just that, since I do not work for the company or in this part of the industry.
#1 New FDA Requirements
Point #1 is not actually stating anything except when the 18 months began.
- Huh? You missed the point here. Point One was New FDA Requirements discovered at the pre-IND meeting including new assays, tests, characterizations. Analytical chemists will tell you development of tests and validations of those tests alone will take 1-9 months or more. Then the company would have had to use these tests on old and new batches going forward to assure reproducibility, consistency, etc.
#2 New Facility Delay
Point #2 might explain why they waited 12 months to start, but per my point above, is inconsistent with them EVER being able to start in '13 as the facility was not EVER planned on being operationally sound until late'13 at the earliest.
- Ref. my previous comment on this.
#3 Assurance of Consistent Manufacturing for Future Leveragability
Point #3 is not relevant to why they started preliminary tox 18 months after their FDA meeting.
- You and I will disagree on this one, but I have seen this be a problem for FDA-regulated companies. After you have all the new CMC and characterization test methods validated (Point #1), you need to take the time to do process optimization and then manufacture multiple lots and test them for reproducibility, capability to specs, and consistency in characterization tests to be sure you don't waste time and money on studies that can't be leveraged for the later, progressively more important testing. Much of this is sequential work, requiring the validations to be complete (months) before the process work (more months).
Bottom line from my point of view - they met their communicated deadline (even if you think they should have beat that) and are on the right track.
OK, hold your opinion. I'll go with NNVC statements in the Sept 2013 Annual Report declared to be truthful to the best of Company Officers' knowledge under penalty of law.
We therefore decided to perform the synthesis of FluCide for tox package in our existing small-scale laboratory. These activities are currently in progress.
Dengue next, yes, but next Catalyst maybe better.
I agree on the Dengue EU Orphan status as most likely next [kudos Puffer and Zinc cause I didn't initially think of that either.]
But I think the next catalyst may be a PR not only stating non-GLP Tox completion, but also announcement of completion of large master batch and initiation of the IND-enabling GLP safety and Tox studies for FDA.
Based on the Annual Report (see excerpt below), Tox Studies (non-GLP and GLP) do not need cGMP materials. For the GLP Tox study, NNVC needs 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. The report says these manufacturing activities are currently in progress [Sept publication of AR] - and so they are either already done or are being completed for the GLP study in parallel with the execution of the non-GLP study.
To clarify (some are getting this mixed up).
- GLP/cGLP speaks to CONDUCTING STUDIES according to current Good Laboratory Practices.
- cGMP speaks to MANUFACTURING MATERIALS according to current Good Manufacturing Practices.
And according to PRs and ARs, NNVC has said they will do the following.
1. Manufacture materials for the non-GLP and GLP Tox Package studies in the existing small-scale facility (not cGMP or cGMP-like).
2. Manufacture cGMP/cGMP-like materials for human clinical studies in the new large-scale facility.
Quote from Oct. 7 PR on start of non-GLP safety and tox study
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. These IND-enabling GLP safety and toxicology studies will be performed by BASi Toxicology Services in West Lafayette, IN. The Company has previously reported that its FluCide candidate was highly effective in animal models of different influenza A virus strains. In those efficacy studies of FluCide, no safety or toxicology concerns were observed. As a result, the required quantity estimated for GLP safety/tox study is much larger than our current synthesis capability. The Company has undertaken process development, scale-up, chemistry optimization and control program to enable large scale synthesis of FluCide in a reproducible manner. This work is currently in progress.
Because of the high level of safety observed in our animal studies, our Safety and Toxicology studies (“Tox Package” studies) have been estimated to require relatively large quantities of materials. This has necessitated that the Company enable scaled-up production and qualify the production processes at a much larger scale than what is needed for small animal studies. Tox Package does not require cGMP materials. Therefore, we have engaged in this scale up at our existing facilities rather than waiting for the cGMP facilities to be completed. We have completed the initial studies to verify that the scaled up production of our Injectable and Oral anti-Influenza drug candidates can be performed successfully.
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.
During the last year, we have also been focused on the design of the cGMP clinical batch production facility and associated R&D laboratories to be commissioned in the Shelton campus.
Thank you, FN.
I looked on the website investors page, but didn't see an Annual Meeting date. Do you have that?
Of course. Thanks, I shouldn't have missed that.
Thanks for flu season info, IN!
I had slightly different dates in mind. The crow pie image in your post is probably for me for assuming flu season dates rather than simply looking them up on Wikipedia to confirm. I was busy looking instead for NNVC public info on clinical trial plans/timing and Australian TGA review statutory requirements for application review times.
The May ending for US extends the date for potential FluCide "materials in the US" into Q2 2015, which would leave more time to achieve in the expedited FDA Reg scenarios.
The Fall 2014 date to start clinical Phase I/IIa in Australia works with the season, although the timing is late in the season - meaning enrollment at a single clinical site may be slower for the efficacy portion for flu-infected patients. But there are only 24 patients total planned (not sure how many healthy patients for safety or sick patients for efficacy), so maybe no significant impact on timing.
But the Boston Biz article where Dr. Seymour has mentioned the Australian submission dependency without mentioning FDA expedited Reg path is still not making sense (maybe Zincfinger or Puffer will come back with more information or someone will contact NNVC?).
And if there is no parallel US FDA path but a dependency on Australia TGA approval, it is still unclear on how much faster application review times may be expected at TGA to meet the article's possible "material in the US for the 2014-2015 flu season."
FYI, if it is not clear, my intent is just trying to understand Reg Paths and milestones potential timing and, if possible, trying to tie that to public information specific to NNVC.
Maybe other folks have NNVC Clinical timing info, also.
Thanks for digging.
Still looking for NNVC public info on Clinical timelines.
ZF your expedited FDA scenario looks sound, but I would like to see Company info from PRs, interviews, articles or presentations to tie it together with NNVC. I haven't seen anything myself. Maybe I never will and need to read between the lines, but I thought I'd at least ask the folks on the message board if they've run across any other NNVC public info references on this.
The potential for inconsistency is that the Feb. 2013 Boston Biz article (earlier post) only stated that Dr. Seymour is discussing getting TGA approval to support FDA approval through "Pandemic and All-Hazards Preparedness Reauthorization Act of 2012" and didn't mention other FDA expedited Reg Paths.
Australian TGA regulatory requirements for New Chemical Entities indicates a statutory requirement to review New Chem Entities in 150 days, but priority evaluations will be completed as quickly as possible and within the statutory requirement, with no further formal paths (AFAICS).
The Australian path may be expedited, or Dr. Seymour may have a parallel path planned for FDA submissions, but again there is no public info I am aware of.
I appreciate your looking into the review timeline examples for previous expedited FDA reg paths (and maybe Australian Reg timing?) to get a better idea on that portion of the timeline.
I would be a bit more conservative on timing of Clinical Report and FDA submission as closer to 3 weeks than 1 (including Clinical trial coordinator data compilation, audits and Australian Biologics Pty. Ltd confirmation of data, data analysis, report writing, final audit, submission writing and NNVC management review prior to submission).
Thanks!
Yes, But US Approval dates don't line-up then. Unless I am missing something?
Does anyone have any other references to publicly disclosed information on dates on the clinical trial besides the Boston Business Journal article from Feb, 2013 I quoted in my post 75248?
The expedited US Regulatory pathway makes sense, but that pathway was not explicitly addressed by Dr. Seymour (he only talked about FDA approval after and dependent on AUS approval) and the dates don't make sense even with the assumption of expedited Reg path.
Namely, Fall 2014 start would be Sept + 1.5 to 2.5mo minimum Phase I/IIa (and maybe Phase IIb) trials would be Nov/Dec + Time for analysis, report, submission and FDA review would be lucky to get done by end of Q1 2015 which would be the end of 2014-2015 flu season.
So the dates don't seem to make sense - unless I am missing something?
Excerpt from Post 75248
Dr. Seymour is quoted with estimated Best-Case ("could") timing as follows
- Fall 2014 start of Phase I/IIa trial - 24 patients - 1-1.5 months
- Phase IIb trial - 100 patients - 1 month
- Phase III trial - 500 patients - 2 months
- "We could have material available in the US for the 2014-2015 flu season."
This last statement is one that would be great for someone to get clarification directly from Dr. Seymour or the company if others on the board don't have references or knowledge to clarify ourselves.
Which of the following does this "material available in the US for the 2014-1015 flu season" mean?
1. Commercial material for sale in US in 2014-2015 flu season after running all 3 trial phases and NDA approval?
2. Clinical material for Phase III trial in the US in 2014-2015 flu season?
3. Or is he considering the upside possibility of great results through Phase II such that FDA grants NDA for commercial sale in 2014-2015 concurrent with Phase III testing?
4. Or was this a typo that was intended to say #1 commercial material for sale in US in 2015-2016.
5. Or was this a typo that was intended to say #2 clinical material for Phase III trial in US in 2015-16.
6. Or that this was updated/corrected in later public information and if so what which public record and what was the update/correction?
FluCide Clinical Trial Plans, Boston Business Journal, Feb, 2013.
Puffer - you probably have a better reference - this one doesn't mention "availability of rooms" and it is a little old - Feb 2013. But it may help inform the discussion here.
Dr. Seymour is quoted with estimated Best-Case ("could") timing as follows
- Fall 2014 start of Phase I/IIa trial - 24 patients - 1-1.5 months
- Phase IIb trial - 100 patients - 1 month
- Phase III trial - 500 patients - 2 months
- "We could have material available in the US for the 2014-2015 flu season."
This last statement is one that would be great for someone to get clarification directly from Dr. Seymour or the company if others on the board don't have references or knowledge to clarify ourselves.
Which of the following does this "material available in the US for the 2014-1015 flu season" mean?
1. Commercial material for sale in US in 2014-2015 flu season after running all 3 trial phases and NDA approval?
2. Clinical material for Phase III trial in the US in 2014-2015 flu season?
3. Or is he considering the upside possibility of great results through Phase II such that FDA grants NDA for commercial sale in 2014-2015 concurrent with Phase III testing?
4. Or was this a typo that was intended to say #1 commercial material for sale in US in 2015-2016.
5. Or was this a typo that was intended to say #2 clinical material for Phase III trial in US in 2015-16.
6. Or that this was updated/corrected in later public information and if so what which public record and what was the update/correction?
Also would be helpful to have this message board or the company clarify whether the durations include only the clinical trial durations or whether these durations include requirements for the following:
- IRB protocol approval
- site initiation and set-up
- data compilation, analysis, write-up of reports
- IRB approval to move from Phase I/IIa to IIb, IRB approval of Phase IIb protocol
- FDA approval of Phase III study design (Ref: FDA website), IRB approval of Phase III protocol
Source: Boston Business Journal, Feb. 4, 2013. Don Seiffert, BioFlash Editor
Link: NanoViricides CEO: $6M could bring potential flu cure to clinic by 2014
NanoViricides Inc. (OTCBB: NNVC) in West Haven, Conn. has raised $6 million from its current investors to bring its potential cure for influenza to clinical trials in Australia.
CEO Eugene Seymour told Mass High Tech that the money will go toward trials of FluCide, a drug candidate that has so far only been tested in animals. The compound is designed to attack the flu virus, not only killing it, but vaccinating the patient against future infection, according to Seymour. A Phase 1 and 2a trial is planned to begin in the fall of 2014, about 18 months after construction work to expand a research lab in Shelton, Conn. begins next month, said Seymour, who said he plans to lease the lab.
Seymour said he has chosen to conduct the trials of FluCide in Australia because the government reimburses 45 percent of research and development expenses, and also requires less paperwork to certify drug manufacturing facilities.
Once human trials begin, they won’t take long, said Seymour: a Phase 1/2a trial involving 24 patients would take about four to six weeks, followed by a Phase 2b trial with 100 patients, which would take another month, and then a Phase 3 trial in about 500 patients would take two more months. While Seymour said that he aims at getting approval abroad first, he said a bill recently passed in Congress, called the “Pandemic and All-Hazards Preparedness Reauthorization Act of 2012,” could mean that if FluCide is approved in Australia, it would potentially be made available in the U.S. in as soon as two years.
“We could have material available in the U.S. for the 2014-2015 flu season,” he said. “Definitely a year later, we would have a hell of a lot more.”
The company has raised $19 million to date. Seymour did not disclose the names of the three investors, saying only that they consist of two physicians and a physics doctorate. Last June, NanoViricides raised $5 million as part of a registered shelf Form S-3 offering from April 2010, which cleared the way for the company to raise as much as $40 million without the need for review by the Securities and Exchange Commission.
He said that he plans to first target patients with compromised immune systems, and he hopes to earn fast-track status by the U.S. Food and Drug Administration. About 50,000 patients die of the flu every year, he said. The company, which has just a handful of employees, also has a number of other drug candidates aimed at other infectious diseases, including HIV, oral and genital Herpes, viral diseases of the eye, Hepatitis C, rabies, Dengue fever, and Ebola virus.
Govt Shut/Slim down won't affect facility progress - at least not that way.
FDA guidance says they may choose to inspect after the IND is filed, before IND approval - not during construction. Although FDA says "may", I would think they would inspect the FluCide clinical manufacturing facility, since FluCide is so novel, but not until after the IND (see cGMP Phase I FDA guidance excerpt and link below).
I am not sure, but it might be the fines Zincfinger mentioned were part of a contract with the builder. Such clauses would be good practice and especially needed if there was any chance that such materials could somehow end up being transferred into the product. Silicones and oils are notorious for spreading all over and getting where you least expect them. The presence of these contaminants in the general manufacturing environment put at risk meeting cGMP requirements for purity (see below).
FDA reviews the submitted IND to determine whether the phase 1 investigational drug to be used in the clinical trial is sufficiently safe to permit the trial to proceed. This determination is based, in part on whether the investigational product has the identity, strength, quality, and purity, and purported effect described in the IND application. In certain circumstances, FDA also may choose to conduct an inspection (e.g., if there is insufficient information to assess the risks to subjects or if the subjects would be exposed to unreasonable and significant risk).
Edit for previous - These are responses (in red) to Nanotoday's post (in black).
Timelines - I address each point in red, Nanotoday.
I was asking about #2 and #3 being done with existing material because you said that that was part of the reasoning behind the delay was "the consistency of the manufactured materials with the various processes would not have been optimized and finalized." Combining that with the theory that they needed to work out the scale up formulations, I am still not clear as to why they would have to wait 18 months.
- I am not sure what you mean here. #1 was lots for non-GLP, #2 was lots for GLP, #3 was cGMP/like lots for Clinical. #3 could never be done with existing materials. Perhaps (not sure) you mistook my statement on "consistency of manufactured materials" to mean all materials have been made? That is not the case, because I stated they still likely need to make lots for GLP and certainly have to make cGMP/like materials for clinicals. If I wasn't clear, I meant that there would need to be confidence that practice runs for the individual unit operations of the larger scale operations were reproducible with manufacturing capability to specs and tolerances and consistent in characterization tests across each of the 3 processes (manufacturing for the non-GLP, GLP and Clinical purposes).
If as you claim, they were originally planning on doing tox (preliminary or GLP) with materials from new plant, then they could have NEVER been started in '13, which certainly was a claim made by the company.
- Not as I claim, but as the 2013 Annual Report claims. But you are right that this seems inconsistent. The early PRs do speak to non-GLP testing, but not specifically as to what the timelines were for non-GLP and GLP. I wish the company was more clear on timelines and specifics as well.
Regarding the 18 month delay. I do not accept your theory.
- I would not call it theory. Rather, it is based on public records and educated assumptions based on analogous industry observations. I admit to my assumptions as just that, since I do not work for the company or in this part of the industry.
#1 New FDA Requirements
Point #1 is not actually stating anything except when the 18 months began.
- Huh? You missed the point here. Point One was New FDA Requirements discovered at the pre-IND meeting including new assays, tests, characterizations. Analytical chemists will tell you development of tests and validations of those tests alone will take 1-9 months or more. Then the company would have had to use these tests on old and new batches going forward to assure reproducibility, consistency, etc.
#2 New Facility Delay
Point #2 might explain why they waited 12 months to start, but per my point above, is inconsistent with them EVER being able to start in '13 as the facility was not EVER planned on being operationally sound until late'13 at the earliest.
- Ref. my previous comment on this.
#3 Assurance of Consistent Manufacturing for Future Leveragability
Point #3 is not relevant to why they started preliminary tox 18 months after their FDA meeting.
- You and I will disagree on this one, but I have seen this be a problem for FDA-regulated companies. After you have all the new CMC and characterization test methods validated (Point #1), you need to take the time to do process optimization and then manufacture multiple lots and test them for reproducibility, capability to specs, and consistency in characterization tests to be sure you don't waste time and money on studies that can't be leveraged for the later, progressively more important testing. Much of this is sequential work, requiring the validations to be complete (months) before the process work (more months).
Bottom line from my point of view - they met their communicated deadline (even if you think they should have beat that) and are on the right track.
No, only non-GLP and GLP Tox Pkg animal studies (#1 and #2) are planned to be done in the existing facility. The human clinicals (#3) will be done in the new facility, which must be cGMP for US trials or cGMP-like (same practices but without FDA designation) for OUS trials, as in Australia which the company seems to have chosen for their FIM (First in Man) trial (old industry term holdover though not politically correct).
While it might be theoretically possible for them to manufacture cGMP-like materials for clinicals in the smaller lab, they have consistently stated in PRs that they plan to make these in the new facility. There may be constraints in the existing labs that prevent or make costly achieving cGMP.
NOTE: I have made an assumption that #1 (non-GLP) are different lots on different scale than #2 (GLP) based on the Annual Report that stated they were still waiting on equipment for the 3-5 batches needed for a large enough composite to complete their Tox Package. It is possible, though I think unlikely, that the statement in the September-30-released Annual Report applied to the June fiscal year end and that in the few months after June 30 they got the equipment, made the batches, completed batch release and characterization testing, blended and batch released the composite batch, and started the studies using one master batch intended for both #1 non-GLP and #2 GLP. As I said possible ... but not as likely.
As for why it took 18 months from pre-IND to initial Tox testing, there are/could be several reasons.
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 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.
NT there are good reasons for waiting to start the non-GLP Tox range finding.
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 manufacturing processes need to have similar CMC with respect to specifications and characterization of the product output.
1. Lab scale for non-GLP Tox range finding
2. Larger lab scale for GLP Tox testing, 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 processes to assure the early tests can be leveraged for the later ones with sound scientific basis that can be used to support 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.
Summary so far on trading in NNVC of those willing to share. ANYONE ELSE?
I will try to keep this up to ~1-1.5 month, before or to ~ Thanksgiving. Started Oct. 9, day stock made huge intraday U-Turn with 7% intraday drop turning flat EOD.
Correct and forgive me if my paraphrasing is incorrect.
(No judgements from me on levels of truthfulness. Board can make its own judgements as to whether truth is full, shaded or obliterated as a means to some end or other)
Rearden ($5.00 Oct. 9 Post 75010) - Invest when cash available, but not throw caution to the wind like Tony Romo! [Cool]
I Need Help ($5.00 Oct. 9 Post 75011)- Adaptable, evaluate every day. Range of from $4.75 to $7.50. The key point as I see things today is that there is much more probable high side potential than downside. Recently bought in. [More thorough analysis in post]
Bloomvest ($5.00 Oct. 9 Post 75012) - Traded NNVC too many times to count and have done very well. Not addressing fundamentals. Could be revolutionary new technology or a total scam. I don't know. As of right now promotions had slowed down so I had sold out 100% of my position. [More in post and board replies]
Thanks, this point on unlikely CI effect on efficacy was also made by ZF in post 75002 and replied to by me in post 75004.
Cheers
Hey bloomvest (and other traders),
Just for the curiosity sake, about how low would the share price have to go before you "old hands" would consider buying in?
Any predictions on whether it goes lower or higher near term (1-2 months) before additional catalysts like announcements on completion of GMP facilities, start of GLP Tox, etc.
Consider it a challenge - a horse race we can all cheer one way or another on our journey.
Cheers
BTW - I pretty much suck at trading, so I can live it vicariously, but maybe I can learn something from others here.
NNVC company doesn't appear to have any competitive inhibition.
FluCide drug's potential competitive inhibition will be arbited by the FDA/OUS Reg based on animal Tox and clinical TK, PK, PD.
My own take on it is to stay invested but keep my eyes and brain open to further evidence on risk/reward potentials.
Do you have any additional evidence to support your point on competitive inhibition to share with the board?
Thanks, ZF, well supported - but one quibble:
This also was ruled out as a potential problem for the drug by the previous animal tests.
The importance of the previous animal tests here is that they have demonstrated that ligands attaching to the drug are not a problem for the drug (because it has so many recptors) and also that the initial reduction in ligands due to some attaching to the drug (soon corrected by up regulation of production of the ligand to compensate) is also not a problem.
Too funny - hadn't heard those in a long while.
:>)
Cool - thanks KMBJN.
Fortunately, from what I understand, provoking an autoimmune response is very rare (although again not zero risk).
It's been interesting to dig into this a little deeper than I covered more superficially in a couple undergrad biochemistry classes many years ago. I know there are PhDs here on the board with much more education and experience.
It's great putting more context around risk/reward for this company and learning a lot from you and others here.
I realize this was to KMBJN (who may have a better answer), but wanted to comment as well.
You may be right that the risks may be lower.
We do not know the chemical changes Dr. Diwan has made to the ligands acting as sialic acid mimics.
As you stated, FluCide is intended (and has been shown in animal studies) to have high binding specificity for the Flu.
These changes may lower the binding specificity for the host's naturally occurring constituents with lower Tox and safety risks.
Regarding your comment:
The second possible concern I have is some kind of immune reaction against the nanoviricides. This is less likely using the PEG backbone, but still a possibility. What if the body started to recognize sialic acid (from the FluCide) as a foreign substance / invader, and the body started to attack all those cells with that receptor?
Thanks for your more thorough explanation and balanced response, KMBJN. We are in the same camp - optimistic but acknowledging some continuing risk.
With sialic acids decorating the surface of all kinds (and species) of eukaryotic cells (incl. bacteria, mammals and people, ), and the number of biochemical pathways in which they are involved, there remains some risk - although likely lower than with intra- and intercellular interacting drugs.
Some sialic acid functions that may (emphasis on "may) be affected by competitive inhibition include:
"biophysical effects regulation of factor H; modulation of leukocyte trafficking via selectins; Siglecs in immune cell activation; sialic acids as ligands for microbes; impact of microbial and endogenous sialidases on immune cell responses; pathogen molecular mimicry of host sialic acids; Siglec recognition of sialylated pathogens; bacteriophage recognition of microbial sialic acids; polysialic acid modulation of immune cells; sialic acids as pathogen decoys or biological masks; modulation of immunity by sialic acid O-acetylation; sialic acids as antigens and xeno-autoantigens; antisialoglycan antibodies in reproductive incompatibility; and sialic-acid–based blood groups."
Source for above:
Multifarious roles of sialic acids in immunity, Cellular and Molecular Medicine, UC San Diego
Good points by LS and ZF regarding much lower than normal risks of animal to human results, which I agree with.
However, I haven't seen discussed here the subject of competitive inhibition. As I understand it, these dose finding studies for non-GLP and GLP Tox will now include much higher doses than studied previously.
These higher doses will increase the interactions of endogenous entities (such as immunomodulators like IgG) with the sialic acid mimics on the nanoviricides, reducing the availability of these necessary constituents for normal biochemical interactions.
Having said that, even this risk is reduced for FluCide which will only be used acutely, allowing the biochemistry to return to normal levels more quickly.
I am always a little cautious and I wanted to put this out there for discussion by experts on the board (no one has said the risks are zero).
BTW I am still invested and don't myself regard these risks as high.
Correction
Ligands of sialic acid mimics are bound to (the outside of) the micelle in the state it circulates in the blood. They are not "bound up in" the micelle, as it wouldn't work that way to bind to the virus.
Question as to whether Tox Studies must run to end of in vivo clearance and any info on degradation/clearance of FluCide or other micelles - For ZF, BK, Puffer or other experts.
Setting aside for a moment the forerunning non-GLP Tox study....
It seems folks think the GLP Toxicity studies will take about 6 months with about 1-3 months for analysis and write-up of the data.
1. Is this a standard length of time for all such studies?
2. Or does it depend on the metabolic clearance rates of the drug and constituents?
For FluCide, it looks from the company's informational materials (although correct me if I am wrong) that the constituents are PEG interspersed with fatty acids with ligands of sialic acid mimics.
I know formal PK/PD studies still need to be done. But looking at the constituents...
PEG is understood to have exceedingly low Tox risk. But while it can eventually be broken down by the body, is not exactly considered readily biodegradable, especially at higher molecular weights.
Fatty acids naturally circulate in the blood (so again low Tox risk), but as they are bound with steric hindrance to the rest of the micelle, they are essentially long chain aliphatics (maybe oligomers?) that are not exactly biodegradeable either (again slower biodegradation at higher molecular weights).
The sialic acid mimics, although also naturally circulating (low Tox risk assuming similar enough), are also bound up in the micelle and so may also be slower to break off and degrade.
So a couple more questions in addition to the ones above:
3. Has there been any information provided by NNVC or in literature on how long it takes the FluCide or FluCide-like micelles to degrade and/or clear in vivo?
4. Is there an expectation to run the Tox until metabolic clearance is complete?
5. Is one of the reasons for the preliminary non-GLP Tox study to determine how long to run the GLP Tox study?
6. Is it possible biodegradation/metabolism/clearance may increase timelines and if so, how much?
Just trying to get more information to inform overall timing to expect for steps to commercialization. Thanks for any help on this.
Good points all. Wasn't overlooking, just wanted to correct my part in misinformation first.
You've made the points better than I would have regarding advantages of early AUS CT.
Looks like a fantastic start on NYSE MKT!
I've confirmed Puffer's and JG36's posts are correct regarding clinical trial prerequisites (in contrast to my own incomplete one with a wrong conclusion for this example - I am still new and wading through all the PRs, etc).
Nov. 13, 2012 PR on Agreement with BASi on Tox studies
The Company has designed the toxicology and safety pharmacology studies that will enable the IND submission and the first-in-human clinical trials of its FluCide® investigational anti-influenza product. BASi will conduct the cGLP and non-GLP studies as required (cGLP = current Good Laboratory Practices). These studies are designed to assess overall safety in animals receiving multiple doses of FluCide. Specific safety pharmacology studies will also be conducted to assess the effects of FluCide® on the cardiovascular, respiratory and central nervous systems. These studies are required for US FDA IND submission, as well as for applications to conduct human clinical trials in other countries such as Australia.
Actually not true - as written.
HUMAN CLINICAL TRIALS MAY BE ABLE TO START IN AUSTRALIA provided the existing evidence of safety from autopsies in preclinical animal trials NNVC has already completed are sufficient to convince either ...
1. TGA (Australian Reg Authority) for a CTX trial path, or
2. HREC (Human Research Ethics Committee) of clinical sites for a CTN path
... to agree that there is enough assurance of safety to proceed with trials.
Correct if amended to say IND human trials cannot start in US without further FDA defined Toxicity Studies.
Based on the AUS consultant firm hire and indications of other posters of clinical trials starting 2014, this looks like the path being taken.
Nanopatent,
I look forward to the Docs and others more knowledgeable on the biology answer more technically and specifically, but...
Although the technology seems to have worked against all the viruses they've tested so far, it is pretty hard to prove a negative.
And although I have bet my hard earned money on the stock representing that tech, I have always been skeptical of the more grand claims by pumpers of the universality of the technology.
Jurassic Park - Dr. Ian Malcolm: "No, I'm, I'm simply saying that life, uh... finds a way." - even viruses.
Thank you, FN.
After my post I should have added that there are no other milestones on Dr. Diwan's list from the NanoManufacturing Summit (or to my knowledge) that are required for starting Tox studies other than making and batch releasing the needed product.
The only remaining task at this point should be making product that meets specs for the studies.
Cheers,
Robi-1-kenobi
Thank you FN - great name - for 'za' nano with the Italian ring.
I hadn't seen that they were producing materials for the Tox studies and that is helpful and positive information. It means that they have gotten through the following (from Dr. Diwan's presentation at Nanomanufacturing Summit 2012 after the FDA Pre-IND meeting).
1. Executable Product Development Plan for Influenza
2. CMC (Chem, Mfg, Controls) Studies [My comment - Would include Critical Quality Attributes and Batch Release requirements]
3. Lab production to 200g scale
4. Assays development
These things can all hold up the start of production to make material for the studies.
And CDER/CBER in FDA can be very prescriptive and proscriptive in all these requirements.
And CQA have to be consistent to know that the material made for Tox studies will be able to be considered equivalent to what they will make for human clinical studies in their cGMP facility.
Thank you to JG as well since his continued prodding brought up this crucial point.
I now think the posters on here are more likely to be right that the uplisting is a precursor to good news.
Robi-1-kenobi (my first post on any BB!)
P.S. Disclosure - I hold NNVC/D but my holding would be chump change compared to most here - a lot to me though. I work on combination drug/device products with some experience dealing with CDER/CDRH - they can slow anyone down.
P.P.S - Gotta love Weedie - he/she always makes me smile!