This document summarizes an innovative anti-inflammatory drug in development by INPHARMA with a novel mechanism of action. It inhibits inducible NO-synthase (iNOS), which catalyzes excessive nitric oxide production during pathological inflammation. Preclinical experiments show potent anti-inflammatory effects with a safety profile superior to existing NSAIDs. The global NSAID market was $10.15 billion in 2010, led by Celebrex. The new drug avoids gastrointestinal adverse effects by not inhibiting COX. The company plans to license the drug after phase I/II trials in 2016-2017, with potential deals of at least $100 million. Required co-investments and grants total $40 million for preclinical development.

1. INPHARMA
Development of an innovative
anti-inflammatory drug
with a novel mechanism of action
– inhibitor of inducible NO-
synthase

2. Problem. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in medicine.
Every year over 300 million people use them. All NSAIDs have one target –
cyclooxygenase (COX), an enzyme responsible for prostaglandin synthesis. Due to this
NSAIDs have adverse ulcerogenic effect on gastointestinal mucosa, possibly causing
dangerous bleedings. NSAIDs use causes 103 000 hospitalizations and 16500 deaths a
year in USA alone.
Solution. Development of an anti-inflammatory drug with a new mechanism of action, not
related to inhibition of COX, will solve this problem. The solution is based on a new
molecule, created under leadership of professor V. Granik. The new molecule is a
derivative of aminoguanidine – the best selective inhibitor of inducible NO-synthase,
bonded with a structural component – a “carrier”, which ensures high bioavailability of the
drug in oral use, high potency and better safety profile.
Technology is based on selective inhibition of inducible NO-synthase (iNOS). This
isoform of the enzyme catalyzes excessive production of nitric oxide, which is a main
mechanism of pathological inflammation. Experiments (on peritonitis models) have proven
the new compound’s potent anti-inflammatory activity. The compound’s safety is proven –
its LD50 > 5000 mg/kg (mice, per os) which is much better than LD50 values of the known
NSAIDs (diclofenac, indomethacin, etc.).
Problem & Solution

3. World market. In 2010 world sales of NSAIDS (Anti-Reumatics, Non-Steroidal, according to
IMS Health data) amounted to $10.15 billion. Sales leader - Celebrex (Pfizer) – $2.49 billion.
Competitors:
1) Classic NSAIDs (non-selective COX inhibitors) –have gastrointestinal adverse effects.
2) Selective COX-2 inhibitors: coxibs (Celebrex, etc.), nimesulide - cause complications of
cardiovascular system, increased liver and kidney toxicity.
Advantages:
The new drug does not inhibit COX activity, so it does not cause adverse ulcerogenic effects
that lead to hospitalizations and deaths of many patients using NSAIDs.
Potential customers – “Big Pharma” companies, interested in market launch of a novel
NSAID – iNOS inhibitor exhibiting high effectiveness, selectivity, high bioavailability in oral use
and good toxicity and adverse effects profile.
Business model provides for licensing the development after finishing Phase I and II clinical
trials in Russia (2016-2017) with transferring rights to a strategic investor(s) (Russian
pharmaceutical company, “Big Pharma” company) for certain markets. Planned volume of
deals (license agreements), including up-front and milestone payments – at least $100 million.
Market & Business model

4. Team
Leader:
Khazanov Veniamin, professor, PhD, an expert in drug development and
commercialization. Since 1991 he has been doing high technology business,
has 20 years of experience in organizing and managing projects of drug
development for medical purposes. Creator and head of “iPhar” group of
companies - one of the leading Russian centers of drug development.
Science team, key persons:
Belska Nataly, PhD - pharmacologist, immunologist. Work experience: Scientific
Institute of Pharmacology of Siberian Branch of Russian Academy of Medical
Sciences – head of Department of Experimental Biological Models, ZAO
“INPHARMA” – director of preclinical trials. Responsibility: organization and
control of preclinical trials of the drug.
Joseph Schwarz, PhD - world-class expert in the fields of pharmaceutical
technology, drug formulation and manufacturing technology (Canada).
Formerly one of the heads of formulation department of TEVA (Israel). Advisor
on pharmaceutical development of the substance and dosage forms of the anti-
inflammatory drug.

5. Project needs
R&D platform
INPHARMA has the necessary resources (laboratories, equipment and staff) for
developing laboratory synthesis technology of the substance for the new
drug, production of test samples for preclinical trials, studying its
pharmacological activity.
IPHAR company is the main partner (R&D platform) for preclinical trials and
dosage form development of the new drug as well as for IP protection issues
and project commercialization. IPHAR has the necessary material
resources, qualified staff and established network of partnerships with higher
education institutes, scientific institutes and clinical centers of Russia, foreign
organizations and specialists from UK, Sweden, Italy, Canada, USA, Israel
and other countries.
Financial needs
Co-investments (about 20 million rub.) and grant funding (20 million rub.) - for
performing preclinical trials of the new drug.