Replies to post #75336 on NanoViricides Inc. (NNVC)

[Puffer]

I think the next thing we hear could very well be Orphan status approval out of Europe for Dengue.

(cGMP facility completion has been pushed into Q1).

[larson1]

Zinc
Wonderful insight. Tox test results should be when. 6 months. March or April. Thanks

[robi-1-kenobi]

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.

Quote from June/Sept 2013 Annual Report, p. 4

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.

Quote from June/Sept 2013 Annual Report, p. 10-11

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.