NanoViricides Inc. (NNVC)

[changes_iv]

As you point out, several things have happened this year, 2015...

Jan. 7, 2015...All of the infrastructure systems needed for production of the nanoviricides® drug candidates are now operational at the new facility, and have either been validated by outside experts, or are in the process of such validation.

http://www.prnewswire.com/news-releases/nanoviricides-inc-completes-purchase-of-cgmp-compliant-pilot-production-facility-300017051.html

Thu, Jan 22, 2015 --- The next phase of the toxicology package studies will involve larger animals, and will require much larger quantities of the drug candidate. The Company is in the process of commissioning operations at the new 1 Controls Drive, Shelton, CT facility in order to perform the scale up studies needed for making the large quantities of materials in a controlled manner. These upcoming studies will be performed in cGLP compliant manner to provide safety and toxicology data that are required for an IND submission to regulatory agencies.

http://www.nanoviricides.com/press%20releases/2015/Nanoviricides%20Reports%20that%20the%20FluCide%20Candidate%20was%20found%20to%20be%20Very%20Safe%20in%20cGLP-like%20Safety%20and%20Toxicology%20Study%20in%20Rats%20Performed%20by%20BASi.html

April 27, 2015...In another news, the Company reports that the process of commissioning of its new facility in Shelton is on course. Our Bio-Analysis Group has already moved operations to the new facility. Large Scale Chemistry Group is completing the necessary modifications to the facility to enable large scale production processes. Various laboratory instruments are being installed by vendors under warranty programs for installation qualification and operational qualification.

http://www.nanoviricides.com/press%20releases/2015/NanoViricides%20Discusses%20the%20Strong%20Effectiveness%20of%20Its%20Anti-Herpes%20Drug%20Candidates%20in%20a%20Lethal%20Animal%20Model%20of%20Dermal%20Herpes%20Infection.html

From TriPhase, a unrelated company dedicated to acquiring and developing novel therapeutics...

Analytical Data Drug Substance

Validated analytical methods are needed to support preformulation, formulation, and pharmacology studies, verification of doses used in GLP studies, cGMP manufacturing, and stability testing of clinical trial materials. It is typically assumed that analytical methods already exist for characterization and identification of the drug substance as this is common in the laboratory synthesis stage of drug discovery. To the extent they exist, the analytical methods must be validated as suitable for analyzing drug substance in the matrix.

If the methods do not exist or are found to be unsuitable for the analysis of drug substance, they will need to be developed as soon as possible so as not to jeopardize the progress of preclinical development.

The analytical method used previously for other [New Chemical Entity] NCE drug substance is likely to be suitable for this novel NCE. [High Performance Liquid Chromatography] HPLC with an external standard is the method of choice. Once validated for drug substance, these analytical methods must be adapted and validated for other sample matrix types, as needed, such as in vitro and in vivo dose samples (see also the bioanalytical method discussion), in-process testing, drug product release and stability testing, and cleaning samples. These methods need to be validated using protocols suitable for In-process development. In general, linearity, accuracy, precision, specificity, range, limit of detection/quantitation, and system suitability must be established. The presence of related substances will also be assessed qualitatively and quantitatively using area%.

Task 6 Analytical Data Drug Substance

6.1Prepare Reference Standard (5g)
6.2Characterize Reference Standard
6.3Document test methods
6.4 Set Drug Substance Specifications
6.5Stability studies of Drug Substance batches

GMP Manufacturing Drug Substance

After the synthesis of two non-GMP batches of drug substance, the synthetic methods should be sufficiently optimized and robust for transfer to the pilot plant if required for the synthesis of the GMP batch of drug substance. This batch, like the previous non-GMP batches, must be well characterized and also subjected to stability monitoring under ICH conditions.

This GMP material will be used for the manufacture of the
formulated drug for the definitive GLP safety toxicity studies including genetic toxicology testing.

The GMP batch will also be used for the manufacture of the clinical trial materials for use in a Phase I trial.

Task 7 GMP Manufacturing Drug Substance

7.1Drug Substance Technology Transfer
7.2Pilot scale GMP batch (1-2 kg)
7.3Quarantine, test, release GMP batch
7.4GMP batch stability monitoring

Develop Formulated Drug for Toxicology Studies

For conducting the in vivo studies detailed in this development plan, formulated drug will be required, including both oral and iv formulations. For all studies except GLP studies, the nonGMP batches will be used for preparing the formulated drug supplies.

The GMP batch will be used to prepare formulated drug for
all of the GLP safety toxicity and genetic toxicity studies required for the preparation of the IND package.

Note however that per the regulations, GLP studies may be conducted with non GMP drug substance providing suitable analytical methods and records are kept so as to be able to compare the quality of these non GMP batches to the quality of your proposed clinical batches.

Task 8 Develop Formulated Drug for Toxicology Studies

8.1Process scale-up solutions and other dosage forms
8.2Develop Specifications for solutions and other dosage forms
8.3Manufacture non-GMP toxicology formulated drug
8.4Analytical characterization of toxicology formulated drug
8.5Continuous stability monitoring of solution or other dosage forms
8.6Manufacture GMP toxicology formulated drug
8.7Stability monitoring GMP toxicology formulated drug
8.8Design prototype capsules (if
not completed above)
8.9Content, uniformity, dissolution, stability
8.10Initial stability monitoring
http://www.triphasepharmasolutions.com/Drug%20Development%20Plan.pdf

Commissioning and validation of a new pharmaceutical facility should be considered the optimal goal, as the ROI is not realized until the facility can make product. Budgets and timelines usually become the target focus through a majority of traditional construction projects, sometimes leaving the commissioning and validation of the facility as the final area of focus [3].
http://www.pharmamanufacturing.com/articles/2004/41/

June 1, 2015, 9:47 PM

FluCide

Phase I and II of tox successfully completed

Making material for last Phase in large animals
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Eugene Seymour MD MPH
Chief Executive Officer
NanoViricides, Inc
[e-mail]
www.nanoviricides.com
310-486-5677
"NNVC" on the New York Stock Exchange

c-GLP or GMP-like?...

Definitive Toxicology Studies

The definitive toxicology studies are a key part of the preclinical development package. Dose levels for the definitive studies will be selected based on the results from the pharmacokinetics and range-finding studies. The definitive toxicology studies must be performed under GLP conditions and (preferably) using GMP material in order to support the IND application.
http://www.triphasepharmasolutions.com/Drug%20Development%20Plan.pdf

Nanoviricides Reports that the FluCide Candidate was found to be Very Safe in cGLP-like Safety and Toxicology Study in Rats Performed by BASi
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This study was developed in collaboration with BASi and conducted by BASi in a c-GLP-like fashion in order to understand the safety parameters of FluCide intravenous dosing...

http://www.nanoviricides.com/press%20releases/2015/Nanoviricides%20Reports%20that%20the%20FluCide%20Candidate%20was%20found%20to%20be%20Very%20Safe%20in%20cGLP-like%20Safety%20and%20Toxicology%20Study%20in%20Rats%20Performed%20by%20BASi.html

The c-GLP Tox Package study will be conducted by BAS incorporated (BASi), a well-known contract laboratory excelling in such studies. As we institute this study, we plan to use the same material for additional efficacy studies of our drug candidate against a number of different influenza virus types, subtypes, and strains. This is required to ascertain the broad-spectrum nature of the drug candidate. Our earlier studies have already demonstrated that this drug candidate is highly effective against both Type I and Type II Influenza A viruses in highly lethal animals studies. We believe that it should be capable of attacking almost any Influenza A virus, because it mimics the sialic acid receptor that all influenza viruses use to enter a host cell. After these studies are complete, and we have the reports in hand, we will be able to submit an "Investigational New Drug" application (IND) to the US FDA. An IND also requires at least two consistent cGMP batches of the drug to have been produced. However, certain international regulatory agencies do not require cGMP product, but rather cGMP-like product. The difference is subtle, but can make a difference of several months. We plan on taking advantage of this and try to request permission for human clinical trials abroad soon after we can make cGMP-compliant product in the new facility. The number of patients that need to be enrolled in a clinical trial depends upon how good the drug is. If the drug effect is very easily separated from the placebo, and more so, from the standard of care, then the trial would require fewer patients to reach the clinical end point of determining that the drug is indeed effective or superior, as the case may be. Therefore we believe, based on the very strong efficacy observed in our animal studies, that our influenza clinical trials will be short, and will be relatively inexpensive.

http://www.nanoviricides.com/2014-ceo-letter.pdf

The difference is subtle...

Facilities and Equipment. Although it generally is not necessary to fully qualify all equipment and validate all processes used in the manufacture of a product during its early development stages, it is important to document which equipment was utilized, why it was selected, and how it was used, cleaned, etc. If calibration of the equipment used to manufacture the product would typically be required in a GMP environment, a similar system is highly desirable at the research and development stage. In short, an intelligent evaluation of which pieces of equipment are critical to the operation should be made as soon as possible, and those critical pieces of equipment should be targeted to achieve compliance with "GMP-like" requirements by the time clinical-grade material is produced. Analogously, if the manufacturing process requires microbiologically-controlled facilities, it is prudent to measure and document the environmental control of these facilities to maintain product integrity and comparability.

Setting priorities for reaching compliance with GMP requirements is an integral part of product development planning. Once critical facilities and equipment have been identified, it is time to establish a schedule for generating compliance documentation. During product development, the move toward full compliance with Good Practice regulations is best regarded as a continuum, rather than a "now nothing, now everything" approach.
http://www.regulatory.com/forum/article/gdps.html

Nanoviricides are currently binary: they either work in humans as they have in animals, or they don't. IMO, there is nothing in between. If they work in humans, then $10 billion will be leaving $40 billion on the table. Pharmassette went for $11 billion with one drug completing Phase 2 and ready for Phase 3. Do the math with that and 5 antiviral drugs plus 200 more in development.~ BigKahuna

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=91019400

Today, that is a valuation of about $50 billion...

"...we are a company...with the ability to rapidly create drugs, and when I say rapidly create drugs I'm talking about weeks instead of years..." ~ Dr. Eugene Seymour, CEO Nanoviricides, Inc.

"by the way, I'm sure that when you think human trials for drugs you think of hundreds of millions of dollars and years of time, well in this case because the disease only lasts a week, two weeks,...that it is possible to complete human trials in the space of a few short months...four parts to the human trials" ~ Dr. Eugene Seymour, CEO Nanoviricides, Inc.

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Example of a FACT...

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