In the continuing search for effective treatments for cancer, an emerging paradigm is the use of nanotechnology to uncap the full potential of existing chemotherapy agents . Integral physicochemical properties of nanovectors can be modulated to improve the antitumor efficacy of chemotherapeutic agents . For example, the shape and size of nanostructures can play a deterministic role in the biological outcome . Similarly, surface modifications to increase hydrophilicity can mask from the reticuloendothelial system, thereby increasing circulation time and altering the pharmacokinetics of the active agents . Such formulation accumulate preferentially in the tumors due to the unique leaky tumor vasculature coupled with impaired intratumoral lymphatic drainage, which contributes to an enhanced permeation and retention (EPR) effect . Indeed, these formulations were shown to deliver between 5–11× more to Kaposi sarcoma lesions than to normal skin . Similarly, the tumor paclitaxel concentration-time area under the curve was found to be 33% higher when administered as a nano-paclitaxel nanoparticle, and is currently approved for use in metastatic breast cancer .
We even took to next level to have nanomedicine engineered with two active molecules, hence making it much more effective than nano-paclitaxel alone. HYBRID-NANOENGINEERING™ IS A NEXT GENERATION OF NANOMEDICINE.
Cancer therapy using cytotoxic drugs has negative side effects on normal cells. To date, the pharmaceutical industry has not been able to produce a drug that can provide the dual functions of protecting normal cells while sensitizing tumor cells to cancer therapy using two or more drugs in one formulation and that too nanomedicine. With the discovery of HYBRID-NANOENGINEERING™, we have discovered a new and better treatment for cancer therapy problem.
Our team is strong and experienced, and all have more than 15 yr industry experience. Our Scientific Advisory Board is composed of experts with a variety of expertise related to drug discovery and drug development.
2. Ongoing path to success
• 1st year Preclinical
IND 26 weeks
2nd Year Safety study in dogs
3rd Year license out to vet market
4th & 5th Year Phase-l and Phase-ll
EXIT
Efficacy in canine
$25M
8-15% Rl
$3M
3. Problem
• Currently, about 30% of drugs that appear on the World Health
Organization (WHO) Essential Drug List were reported to be poorly
water-soluble, based on the Biopharmaceutics Classification System
(BCS) .
• Over 40% of newly developed pharmaceutically active substances
have solubility issues.
• The poor dissolution and/or permeability of these drugs often result in
low and highly variable bioavailability.
• The major obstacle of successfully commercializing these
compounds is the difficulty of enhancing their dissolution rate and
extent of dissolution
4. More Specific Problems
• In a word: bioavailability. As much as $40 billion is invested annually in drug
discovery. Unfortunately, many of the drug leads that result exhibit poor water
solubility and an inability to deliver therapeutic agents in vivo. In fact, it's
estimated that 40-50 percent of these new chemical entities are poorly water
soluble. (which leads to a number of otherwise promising technologies to be
abandoned)
• Despite the solubility issue, worldwide sales of poorly soluble drugs are about
$108 billion and it is going to increase further. It is reasonably expected that
improving water solubility would only increase this number.
• The result is inefficiency in the R&D process. Due to the challenges of
evaluating efficacy in biologic models for a poorly bio-available
compound, these compounds are often shelved with no further development
activity—even if they show promising therapeutic activity in cell culture.
• Meda’s hybrid formulation technology addresses this problem by improving
water solubility, bioavailability, effectiveness and efficiency.
• Poor water solubility for many drugs and drug candidates remains a major
obstacle to their development and clinical application. Conventional
formulations to improve solubility suffer from low bioavailability and poor
pharmacokinetics, with some carriers rendering systemic toxicities (e.g.
Cremophor1 EL).
5. Available Solutions & Limitations
Here are some basic pluses and minuses of the different options.
• pH adjustment is the best option if you can get decent solubility and good stability within a reasonable pH range. Although you have probably
heard pH 4 – pH 10 batted around, there is really no fixed range of acceptable pH. It depends on rate, duration, and route (small vein versus
large vein) of administration and on the buffer capacity of the formulation.
• Cyclodextrins are the next best option in terms of safety and ease of preparation, but until someone forks out the cash for a good enough
lawyer to challenge the very questionable Jannsen/J&J patent on hydroxypropyl-beta-cyclodextrin, there will be licensing arrangements and
royalties involved. Nephrotoxicity is the primary physiological issue associated with cyclodextrins, but as long as you don’t give too much too
fast, you should be okay.
• Co-solvent formulations typically require very high concentrations of co-solvents, and these formulations are not dilutable without precipitation.
Because of their high osmolality, these formulations must be administered through a large vein, where there is good blood flow.
• Micellar formulations are easy to prepare but have a major liability, which is that they tend to cause the occasional patient to go into
anaphylaxis. In many cases a drug can be dissolved in a mixture of a solvent and a surfactant such as Cremophor or Polysorbate to provide a
dilute-for-use formulation. Generally patients will need to be pre-dosed with steroids and antihistamines so that the drug product doesn’t
accidentally kill them.
• Emulsions and liposomes have generally low toxicity profiles but are a pain to make. Liposomes tend to have a lot of physical stability issues
and are typically lyophilized. However, this is good and bad since, unlike emulsions, they can be lyophilized quite easily. The one caveat to
the good safety profile of these formulations is that they can cause hyperlipidemia and liver enzyme elevation if too much is administered too
fast.
• Analytical Methods
The main analytical consideration specific to poorly soluble drugs is being sure that the sample preparation solvent will fully dissolve the drug
without, of course, messing up the chromatography. Another consideration is that in doing particulates testing (USP<788>) you will be looking
not only for foreign particles but for precipitated drug as well. The microscopic method of USP<788> is helpful in determining the difference
between the two.
• Preclinical Testing
You need to be wary of the effects the formulation can have on different species of animals in selecting toxicology species. For example, dogs
are particularly susceptible to surfactant-induced anaphylaxis and cannot be used for evaluation of micellar formulations.
6. What We Offer
• New concept and new approach
• There have never been used two active molecule in
nanomedicine
• There have never been developed a hybrid nanomedicine
• There have never been used an active molecule to
developed a water soluble drug formulation
• Two water insoluble drugs have never been used to
developed a water soluble formulation, at least without
changing the chemistry
• Chemistry of individual drugs remains unchanged
• IT IS NOT JUST SOLUBILITY BUT A BETTER
TREATMENT
7. Success: Technology Parallel in Humans
• Hybrid-Nanoengineering™
• Like Abraxane approved for human
• Doxil
• In process to raise $25-26M for human trials
8. Hybrid-Nanoengineering™
Technology Advantages
• New discovery and patented
• Synergistic effects
• Potentiating effects
• Passive targeted nanomedicine
• Less toxic
• Low manufacturing cost
• Multiple mode of action
A major driving force in the hybrid drug development community is to overcome one of the worst things that can
happen to a drug: the development of resistance in its target population. In most such hybrids, the two drug like
portions, also called pharmacophores, have independent modes of action that make the emergence of drug resistance
less likely.
12. Next Steps
• cGMP manufacturing and pre clinical
• Determine maximum tolerated dose, safety and
therapeutic efficacy
• Evaluate efficacy in canine indications
• Perform a Phase I clinical trial in companion dogs
presenting with ……..
• Human clinical
• Approvals
13. Road Map To Clinical, Funding And Exit
MewTaxel (Hybrid-Paclitaxel)
2013 2014 2015 2016 2017
Clinical
Financial
Seed
Round
$1M $5M $5-7M $10-12M
Final
Pre-Clinical
A
Round
File
IND
Phase-I
B
Round
Phase-II
C
Round
Exit or
Move to NDA.
At this point we
have multiple
options for
FundingProject has a potential of
$500M if Exit after NDA
14. • PROOF OF CONCEPT ------ESTABLISHED
• R & D----------------------------ESTABLISHED
• PILOT SCALE MANUFACTURING ---ESTABLISHED
• IN-VITRO STUDY---PRELIMINARY TESTING ESTABLISHED
• Pre clinical--------------
• Phase-l
• Phase-ll
MewTaxel
15. Why Paclitaxel?
• There are 1989 ongoing clinical trials
associated with Paclitaxel in various
combinations and formulation
compositions. Among them 83 are with
nanoparticles. This reflect a further
growth of the product.
16. Team
• Dr.Mewa Singh- 15 years of drug discovery
• Dr.Timothy A,M.D-20 years drug development
• Dr.Khushi Matta- 40 years of cancer research
18. Technology
• The technology comes under
nanotechnology : Nanotechnology is
science, engineering, and technology
conducted at the nanoscale, which is about 1
to 100 nanometers.
1- 1000000000
Nano
Nanotechnology
19. Why nanotechnology ?
• To increase the surface area to come in contact
with target, more means efficacy, penetration
and concentration
22. Overview of available Nanotechnology
1. Nephrotoxicity is the primary physiological issue associated with cyclodextrins.
2. Does not work with every drug like that.
23. Overview of available Nanotechnology
• Micellar formulations
1. Generally patients will need to be pre-dosed with steroids and antihistamines
2. Toxic
Detergent. oil etc.
24. Overview of available Nanotechnology
• Emulsions and liposomes
1. cause hyperlipidemia and liver enzyme elevation
2. Expensive manufacturing
3. Tailored for individual molecule
25. Why after Abraxane is success?
• The data from the study, presented at ASCO
by lead investigator Hope Rugo at the
University of California, San
Francisco, stated that median progression-
free survival was 10.6 months for those
receiving paclitaxel, 9.2 months for nab-
paclitaxel, and 7.6 months for ixabepilone.
26. Vision…Strategy……Approach
• Hypothesis and Vision: I was looking to take
nanotechnology to next level by;
a) Hybrid in nature to achieve better potency
b) Different material to create nanomedicine
c) Less expensive to manufacture
d) To beat the state being in use
but a rose is a rose and is still a rose almost 400 years after Shakespeare’s death. Basically, there are still
only a small handful of ways of solubilizing a drug and still not killing the patient. These include pH
adjustment, co-solvents, molecular complexation agents (cyclodextrins), micellar
dispersions, emulsions, liposomes, but really not anything else. If anyone knows a truly different method
not listed above, please let me know.
We have beaten this statement by our invention.
27. Discovery
• Discovered a universal molecule to be used
for nanomedicine development.
• The molecule is a drug in nature.
• The molecule has a capability to treat cancer
• The molecule has never been used to create
nano particles.
• Beat me-to concept
• Many more properties…….
33. Specific Application for Paclitaxel
• Why it is better than other available Nano
formulations specially Abraxane;
• It is less expensive to manufacture
• It is attacking the disease by multiple mode
of action
• It gave more life to branded
