White Paper; ValChem, Drug Implants

Developments:
1. New Tb Drugs: Our group developed a novel approach that takes an existing first and second line
antibiotic for tuberculosis and makes them work better against latent and active Tb and allows
them to work again against resistant strains of tuberculosis. Because these drugs (i.e. isoniazid,
capreomycin) have been on the market for decades, they are inexpensive and well understood by
the medical community, so their continual use is both an economic and medicinal advantage. The
inhibition data indicates the dose would drop significantly for the drugs (see attached appendix).

2. Implant: Currently Tb patients for latent, active and resistant strains of Tb take a significant
amount of pills, and in some cases shots, on a daily basis for 6 to 18 months. Many countries
have set up DOTS programs, a daily program where patients go to a health facility every day to
take their medications in front of medical personnel. This is limiting in many ways. Because our
new complexes require significantly lower doses (see appendix) they can potentially be implanted
every 30-60 days and take the place of the daily pills and shots. Because the doses are lower,
many of the horrific side effects should decrease also. The implants are biodegradable, low cost
and made of an inert material. We are currently developing a patent application for this implant.

3. Evaluation: Our in vitro and pharmacokinetic evaluation was obtain by an independent

organization that is a world leader in Tb research. Several of our published papers on drug
development can be found on Google scholar.

4. Other Drugs: Worldwide there is a three pronged epidemic of Drug Resistant-Tb, Cervical
cancer (HPV) and HIV, the spread of the diseases is linked. We have developed a new line of
cancer drugs that have been through pre-clinical trials at the National Cancer Institute. We have
proposed using them for cervical cancer that is correlated with HPV, now the world’s leading
STD. We are also working on an economical synthesis of the HIV drug bryostatin, which can
complement an antiretroviral by knocking out reservoirs of HIV (a single 10 ug dose of bryostatin
now cost 170 USD; or 17M USD/g). Our economical and green bryostatin synthesis involves
growing bacteria in the ocean, not a complex and expensive lab based approach.

ValChem, Valdosta State University

Valdosta, Georgia, USA
Olivia Moss, Marcus Diaz
Dr. Tom Manning
 White Paper; ValChem, Drug Implants

Appendix A. Advantage
If a capreomycin dosage is one gram per day, it can result in significant side effects. It is often
given when front line antibiotics no longer work against due to antibiotic resistance.

First our copper-capreomycin complex (above: Cu-CAP for RMP resistant) had an efficacy over
200 times lower than pure capreomycin against resistant strains. This relationship would lower
the dose to 5 mg per day. Specifically, dose is directly proportionally to MIC by1;

Dose= (Cmax * Vd) / F

Cmax = highest concentration in plasma, calculated as MIC x 2(dose interval/half-life), or

Dose= (MIC x 2(dose interval/half-life) * Vd) / F
Using an implant and placing it in a location where it can take drug straight to the lung should
have an increase in drug delivery efficacy compared to a tablet entering the GI of at least 2 to 5
times. Combining our implant with the efficacy gained from the CuCAP complex, the dose
needed would be 500-1000 times lower. This translates into a 1-gram implant with 100 mg of
capreomycin could deliver for two months, assuming 1-2 mg released per day. The lower more
efficient dose may/should also lower side effects dramatically. Note that CuCAP is effective
against more than one resistant strain.
Our INH complexes also show greater efficacy (lower MIC values) against active and
resistant MTb strains.
https://amrls.cvm.msu.edu/integrated/principles/pharmacology-3-of-3