VISION

META CORPORATIONTheRx

(holding company)

Self funded

License patents from UW

1. Docking with dynamics, multitargeting, new use, herpes, malaria, HIV (JVMS)2. Structure determination using mass spectroscopy and crosslinking (S)3. Greatly improved version of (1) (BeCS)4. “Growing” inhibitors using medicinal chemistry rules (McS)5. Complete discovery pipeline in silico from inhibitors to drugs (McS)6. Biomimetics/protein design for nanotechnology (OTSaS)7. Target identification using Bioverse (several members)

Be-Bernard; B-Bumgarner; C-Cheng; J-Jenwitheesuk; H-Hung; L-Lagunoff; Mc-McCully; M-Mittler; N-North; O-Oren; T-Tamerler; S-Samudrala; Sa-Sarikaya; V-Van Voorhis

SamudralaJenwitheesukLagunoffVan VoorhisBumgarnerNorth (CEO)…

Initial owners VC funded subcorporationsPartnerships

Herpes therapeutics (LJS)Malaria therapeutics (VJS)HIV therapeutics (MSJS)Inhibitor new use platform (NJS)Target determination platform (HS)Novel inhibitor platform (BeMcCS)Drug discovery pipeline in silico (N?S)Biomimetics (OTSaS)…Involvement choice; all current owners will benefit;

easy to add new inventors/contributors

DISTRIBUTION

Samudrala - more than 14 years of research/experience- millions of dollars of funding basic and specific research- coinventor of all patent claims (including to-be-filed patents)- codeveloper of business model since beginning (2+ years)- will fund initial startup costs ($50,000+)

Jenwitheesuk - implementation and coinventor of first and major patent (primary postdoc)- application to > 100 targets, 20+ diseases- superlative work

Lagunoff - several years of research/experience- millions of dollars of funding basic and specific research- coinventor of all herpes-related claims

Van Voorhis - several years of research/experience- tens of thousands of dollars of funding basic and specific research- coinventor of all malaria-related claims

DISTRIBUTION

Bumgarner - creation of four previous corporations (including Rosetta)- tens of thousands of dollars funding specific research (including sysadm)- conceptual development of several patents- codeveloper of business model since beginning (2+ years)- establishment of several important contacts- full engagement in dog and pony shows- long term management- responsible successful execution- will fund some startup costs (including travel to dog and pony shows)

North - several years of business experience- CEO of corporation(s) and legally fiduciarily responsible for all actions- developed business model and will engage in superlative sweat equity- initially will work with Stoel-Rives to form corporation- negotiate share holder agreement- negotiate licenses from UW- full engagement in dog and pony shows- long term management- responsbile for successful execution- will fund some startup costs; possible angel investor

DISTRIBUTION

Samudrala (38% + 25% of patent royalties; vest in 4 years)- more than 14 years of research/experience- millions of dollars of funding basic and specific research- coinventor of all patent claims (including to-be-filed patents)- codeveloper of business model since beginning (2+ years)- will fund initial startup costs ($50,000+)

Jenwitheesuk (16% + 25% of patent(s) royalties; vest in 4? years)- implementation and coinventor of first and major patent (primary postdoc)- application to > 100 targets, 20+ diseases- superlative work

Lagunoff (10% + 25% of patent(s); royalties; vest in 4 years)- several years of research/experience- millions of dollars of funding basic and specific research- coinventor of all herpes-related claims

Van Voorhis (10% of 25% of patent(s); royalties; vest in 4 years)- several years of research/experience- tens of thousands of dollars of funding basic and specific research- coinventor of all malaria-related claims

DISTRIBUTION

Bumgarner (13%; vest in 4 years)- creation of four previous corporations (including Rosetta)- tens of thousands of dollars funding specific research (including sysadm)- conceptual development of several patents- codeveloper of business model since beginning (2+ years)- establishment of several important contacts- full engagement in dog and pony shows- long term management- responsible successful execution- will fund some startup costs

North (13%; vest immediately)- several years of business experience- CEO of corporation(s) and legally fiduciarily responsible for all actions- developed business model and will engage in superlative sweat equity- initially will work with Stoel-Rives to form corporation- negotiate share holder agreement- negotiate licenses from UW- full engagement in dog and pony shows- long term management- responsbile for successful execution- will fund some startup costs; possible angel investor

AGREEMENT

Have really tried hard to be as fair as possible; trust is important

Time spent as necessary to make corporation work (in strict accordance with UW policies)

Some minimal cost for ownership (1/100ths of penny a share for example)

Additional shareholders (UW, Samudrala and other group members, other interested parties based on agreement of corporation majority and percentages reduced accordingly

Potential names include TheRx, Rxtacy (kidding), RxSeed, etc.

Need to file outside work requests (Chair, Mike Corn, Provost); speed of approval is greater if all requests are filed at once; will assist

Then: Stoel-Rives, form corporation, shareholder agreement, negotiate with UW for licenses, obtain VC funding, obtain collaborations

Do not get hung up on initial distributions; there will be dilution and greatest potential for individual reward is commensurate with involvement in subcorporations and their success, though all initial owners will benefit even if one success occurs

JASON NORTH – BACKGROUND AND EXPERIENCE

Background:- Have known Ram for 10+ years; long term plans coming to fruition

Professional experience:- 10+ years of business experience- Extensive experience in management of exit strategies of several startups- Sales at EnterpriseLink (acquired by Merant)- Management at UpShot (acquired by Siebel)- Executive at Liquid Development- Consultant at Digidesign

Highlights:- Business development and negotiations of 30+ million dollars- Involvement in industries such as a software, insurance, and healthcare- Extensive mentorship from Foster North (CEO, Third Millenium)

JASON NORTH – PLANS

Immediate plans as soon as UW team is ready:- Work with Stoel-Rives to complete paperwork to form TheRx- Help organise and negotiate shareholder agreement- Negotiate license of initial patent from the UW in the best interests of TheRx- Vigourously explore VC funding and partnership opportunities- Execute formation of subcorporations as necessary with Stoel-Rives- Develop solid business plans and executive summaries- Negotiate and execute VC and partnership deals

Intermediate term plans:- Continue negotiations of other patents from the UW- Continue shopping IP to VCs, Pharma- Enable TheRx to grow and become financially independent- Retain control of platform technologies as necessary- Enable TheRx to supplement funding of UW inventors’ groups- Open opportunities for owners to take pivotal roles in subcorporations

Future:- Will give all to revolutionise pharmaceutical industry model with your support

APPLICATION: DRUG DISCOVERY

HSV KHSVCMV

Jenwitheesuk

APPLICATION: DRUG DISCOVERYConcentration

Res

pons

e

APPLICATION: DRUG DISCOVERY

HSV KHSVCMV

Computionally predicted broad spectrum human herpesvirus protease inhibitors is effective in vitroagainst members from all three classes and is comparable or better than anti-herpes drugs

HSVHSV

Our protease inhibitor acts synergistically with acylovir (a nucleoside analogue that inhibits replication) and it is less likely to lead to resistant strains compared to acylovir

Lagunoff

APPLICATION: DRUG DISCOVERY

Jenwitheesuk/Van Voorhis

APPLICATION: DRUG DISCOVERY

We experimentally evaluated 16 of our top predictions against P. falciparum in cell culture. 6/16 had an ED50 of 1 M, with the best inhibitor having an ED50 of 127nM.

A negative control of 5 randomly selected compounds predicted to not inhibit our fourteen targets did not inhibit P. falciparum growth.

Chong et al.1 experimentally screened 2687 compounds and found 87 inhibitors against P. falciparum. Weisman et al.2 screened 2162 compounds found 72 inhibitors. Their hit rates are 3.2% (87/2687) and 3.3% (72/2162).

We are thus able to obtain a much higher hit rate of 38% (6/16) for a fraction of the cost: Only 16 compounds costing ~$1000 needed to be tested. Computation is fully automated and takes only a few days.

Examining overlap between our computational library and their experimental libraries resulted in 75 compounds of which we would have tested 15. 8/15 inhibitors had an ED50 of 1M, resulting in a hit rate of 53%.

1Nat Chem Biol 2: 415-6, 2006.2Chem Biol Drug Des 409-16, 2006. Jenwitheesuk/Van Voorhis

APPLICATION: NANOTECHNOLOGY

Oren/Sarikaya/Tamerler

APPLICATION: SHOTGUN STRUCTURAL PROTEOMICS

Add crosslinkers

Repeat using different crosslinkers and isotope labelling

Identify crosslinked fragments

MS

MKRS

LVKQ

VSKNT

KEVN

Confirm sequence

MS

Identify proteins with single crosslinks and fragment

MS