Investors

Oyagen Inc. Corporate Summary

Overview

OyaGen has its origins in the science of RNA and DNA editing enzymes, their interactions and their regulation through the academic work of Dr. Harold C. Smith, University of Rochester, Rochester, NY (http://dbb.urmc.rochester.edu). Founded by Dr. Smith in 2003, OyaGen, Inc. holds Intellectual Property (IP) licensed from Thomas Jefferson University, the University of Rochester, Oregon Health Sciences Center and Vybion Inc. in addition to Company’s self-generated IP. Initially, OyaGen is focused on the discovery and development of therapeutics for the treatment of HIV. The Company has identified 5 unique druggable targets on HIV which attack the virus and/or strengthen the innate cell defense. Successful development of drugs that address these targets will offer patients first-in-class alternatives to current HIV therapies and bring the Company attractive potential financial returns.

HIV Market

Brief Summary: HIV remains a significant health care issue with 33 million people worldwide affected, 1.5 million in the USA and EU. The market is expected to continue to show sustained growth despite advances in controlling the progress of the disease (Cowen & Company). The incidence of HIV continues to grow at a double digit rate in developed markets according to the U.S. Center for Disease Control. Patient treatment remains low. ~30% of USA patients are unaware they are HIV positive and only one third of HIV positive USA patients receive treatment. While treated patients have longer survival, the failure rates for current frontline therapies are 10% and ultimately the virus ability to mutate continues to demand new drugs. New first-in-class HIV drugs continue to achieve blockbuster annual sales. Merck’s new integrase inhibitor (Selzentry) is expected to reach $2B in annual worldwide sales by 2015 (Cowen & Co.) despite narrow labeling.

Human immunodeficiency virus type 1. HIV-1 (HIV) is a lentivirus and the causative agent of AIDS. At the end of 2011, there were approximately 34 million people infected with HIV worldwide, with 2.5 million new infections. Infection rates are on the rise not only in under-developed countries but in high-income nations as well. This is demonstrated by the fact that, in 2011, there were an estimated 1.4 million people infected in North America alone, which is a 22% increase from 2001 (http://www.unaids.org). Thus, one of the goals set by UNAIDS is to decrease sexual transmission of HIV by 50% by 2015, which will be aided by the development of novel prophylactic strategies. One potential mechanism for preventing HIV transmission is to activate a known host defense factor, APOBEC3G (A3G). Active A3G binds to viral single stranded DNA (ssDNA) and deaminates dC to dU, leading to hypermutated viral genomes and non-infectious virions. Targeting host proteins is often avoided due to the concern of toxic side effects. However, A3G is restricted to the cytoplasm [6], has no access to genomic DNA, and has no known cellular DNA substrates, making it a good therapeutic candidate. Activation of A3G enzymatic activity represents a novel preventative strategy and may be accomplished using a vaginal gel containing a small molecule A3G activator (SMAA). In addition, activating A3G in an infected individual holds the potential to be functionally curative as either a stand-alone treatment or in conjunction with additional treatment strategies.

HIV prevention, treatment, and the need for novel therapeutic targets. In 1984, scientists at the US National Institutes of Health (NIH) and the Pasteur Institute determined that HIV was the virus that causes AIDS. At that time, it was declared that a vaccine would be available within two years. Nearly 30 years later, there remains no vaccine candidate and, in fact, NIH recently halted an HIV vaccine trial over concerns that more study participants became infected after receiving the test vaccine than those who received placebo. Thus, the only current hope for preventing HIV infection has come from Gilead’s combination treatment, StribildTM. This medication is a combination of 3 components of the current highly active anti-retroviral therapy (HAART) regiment (elvitegravir, an integrase inhibitor; emitracitabine and tenofivir, both nucleoside reverse transcriptase inhibitors) along with cobicistat (a pharmacokinetic enhancer of elvitegravir) (http://aidsinfo.nih.gov/guidelines). However, resistance to all three of these inhibitors had already emerged prior to combining and using them as a preventative (http://www.aidsmap.com), suggesting the same is likely to happen while using them to prevent HIV infection. In addition, if an at-risk individual is exposed to a strain resistant to any or all of the StribildTM components, there will be little chance for protection.

Not only has HIV developed resistance to the drugs currently in use as prophylactics, but also it has developed resistance to all HAART medications to date, including inhibitors of reverse transcriptase (RT; nucleoside and non-nucleoside), protease (PR), integrase (IN), and viral entry. The barrier to developing resistance to HIV drugs is low and, often times, a single codon change in the targeted protein is sufficient to cause resistance to more than one inhibitor of the same class (i.e. M46I/L/V in the PR enzyme confers resistance to 7 out of 8 inhibitors; http://www.aidsmap.com). To thoroughly emphasize this problem, ViiV Healthcare currently has a new IN inhibitor (dolutegravir) in Phase III clinical trials and in vitro passage experiments demonstrated the emergence of resistant viral strains after only 14 days. The ever-present problem of drug resistance together with the lack of success in developing an HIV vaccine underscore the need for novel prevention and treatment strategies that are unlikely to develop resistance, such as targeting the A3G host defense factor.

The discovery of A3G as an antiviral factor and its mechanism. A3G was discovered as an HIV restriction factor during studies of the HIV Vif (viral infectivity factor) protein. Vif is a 23 kDa phosphoprotein that is expressed late in the viral life cycle. In the absence of Vif, HIV cannot establish a spreading infection in non-permissive cells (i.e. CD4 cells and macrophages). However, Vif expression is not required for infection of permissive cells (i.e. 293T, HeLa, and COS cells). Heterokaryons formed between permissive and non-permissive cells were infected with Vif-deficient virus and the resulting progeny virions were determined to be non-infectious, demonstrating that cells expressed an anti-HIV factor that was overcome by Vif expression. Subtractive hybridization experiments by Sheehy, et al identified A3G as the antiviral factor.

A3G is a member of the cytidine deaminase family, all of which demonstrate either DNA or RNA editing activity. This was the first indication as to how A3G was functioning as an antiviral. Further studies determined that, in the absence of Vif, A3G is incorporated into HIV virions and, once encapsidated, A3G binds to the viral core. During viral replication, A3G extensively deaminates viral minus-strand DNA, converting dC to dU. This hypermutation of the viral DNA leads to one of two outcomes: 1) viral DNA is destroyed by DNA repair enzymes or 2) the mutated minus-strand DNA serves as a template for plus-strand synthesis whereby aberrant dU residues lead to dG to dA transitions. This alters the viral open reading frame, leading to the introduction of premature stop codons and missense codons. Each situation leads to the generation of less infectious virions and, thus, a decrease in HIV infectivity.

OyaGen’s Approach and Pipeline

The Company has developed proprietary primary and secondary screening assays for the identification of small molecules affecting 5 HIV targets that involve an editing enzyme (APOBEC3G or A3G) and its interaction with an HIV protein Vif as well as the interaction of Vif with CBFβ and the ubiquitination machinery.

The Company has early lead scaffolds from medicinal chemistry for Vif Dimerization and A3G Activation that have demonstrated nM anti-HIV activity and uM cytoxicity.

Intellectual Property

The OyaGen patent estate is extensive and covers unique opportunities for OyaGen to commercially exploit its important new HIV therapeutic targets with several first in class drugs. The Company’s intellectual property provides strong protection from competitors for development of other molecules that act on the Vif/hA3G interaction, APOBEC3G (A3G) activation and target-specific assays .

OyaGen Resources

The Company currently occupies 3,000 sq ft of state of the state of the art laboratory within the Rochester BioVenture Center in Rochester NY. A broad range of advanced instrumentation, controlled environments, small molecule libraries and a BLS2+ facility enable in-cell and cell-free assay development, infectivity and other functional endpoint analyses and high throughput screening at our current rate of 5,000 compounds/assay/day.

The Company has a management team and external advisors with extensive experience in Biopharma and the Life Sciences. The management team is supported by a world-class Scientific Advisory Board including global leaders such as Dr. David Ho, CEO of the Aaron Diamond AIDS Research Center at Rockefeller University (NYC) who was a Time Magazine Man of the Year and one of the world’s leading HIV authorities; Dr. Thomas Chung, Director of Outreach & Project Manager, at Sanford/Burham Conrad Prebys Center for Chemical Genomics and Dr. Robert Buckheit, CEO of ImQuest BioSciences.

Current Financing Activity

OyaGen is currently seeking to raise up to $5M to support the on-going lead optimization work and preclinical development which will position the Company for the more extensive animal toxicity testing necessary to file an Initial New Drug Application. The Company expects to obtain long term financing through Venture Capital firms, strategic partnerships and Federal and State grants which will provide the financial resources to complete development of clinical compounds. In addition the company is seeking support and financing through Phase II of clinical trials.

Future Opportunities

In addition to its HIV pipeline, OyaGen has a High Content Screen (HCS) at near completion for the identification of compounds that will prevent malignant progression in follicular lymphoma. The assay is based on the editing enzyme Activation Induced Deaminase (AID). The Company also intends to advance A3G activators in HTS assays for compounds that prevent the emergence of steroid hormone-independent recurrence of prostatic cancer as well as antiviral therapeutics for hepatitis A, B and C.

Specific inquiries should be directed to:

Thomas Fitzgerald, COO OyaGen Inc.
77 Ridgeland Road
Rochester, NY 14623 USA
Telephone: (585) 413-9070
Cell: (585) 766-3617
E-mail: tfitzgerald@oyageninc.com
Dr. Harold C. Smith, Founder, CEO and President OyaGen Inc.
77 Ridgeland Road
Rochester, NY 14623 USA
Cell: (585) 697-4351
E-mail: harold.smith@rochester.edu