1 Right-Sizing Automation for Medicinal Chemistry Support your entire department with One-Minute NMR TM Fun Easy Robust Fast Efficient Economical Controllable Flexible Copyright © 2006 by Protasis Corporation, All Rights Reserved

2 Enhancing Your NMR Investment Get the most from your instruments Easy Open Access Web login for vials and plates reduces time spent in the lab. Automated System Suitability and Maintenance provides assurance of good spectra. Microgram Samples avoids return trips to the lab and enables scale-down upstream in your workflow. Plate and Vial Submission simplifies reformatting and sample preparation. Closed-Loop Instrument Control enhances NMR error reporting Integrated ACD/Labs and One-Moon Scientific back-end software eliminates manual processing steps.

3 Answers Needed From NMR Copyright © 2006 by Protasis Corporation, All Rights Reserved Source: Survey of 40+ Industry and Academia by Protasis Corporation Bonus: yield (ERETIC) Percentage Of Samples

4 What is it? Everyone wants a magic wand! Leap/CTC PAL Liquid Handler CapNMR Probe NMR Spectrometer ACD/Automation Server Or Web Site You Just Log In Samples One-Minute NMR Manages The Details ACD/Web Librarian Did I make it? Yield? Copyright © 2006 by Protasis Corporation, All Rights Reserved

5 Use CapNMR Log-in Samples…

6 Walk away… Let One-Minute NMR run your sample

7 Click… Seconds Later… In your InBox Hot-linked report Integrated ACD/Web Librarian Copyright © 2006 by Protasis Corporation, All Rights Reserved

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11 LEAP PAL Fast Low Volume Pickup Low Dead Volume Syringe-Only Technology Flexible Sample Storage Dilute / Reconstitute Sample Return Copyright © 2006 by Protasis Corporation, All Rights Reserved

12 Effortless Solvent Management Vacuum Degasser –Smooth MicroFlows Helium Sparging / Blanketing –Protect Expensive Deuterated Solvents Copyright © 2006 by Protasis Corporation, All Rights Reserved

13 HTSL High-Pressure Pumping System

14 NMR Instrument Automation Your spectrometer is controlled and Monitored by the One-Minute NMR system. SEND: Commands to start experiments Create sample directories Query file locations Molecule files RECEIVE: Status messages Error messages File locations You get Finished Notices Plate maps with integrated processing software. Error alerts from NMR, Liquid Handler, etc. On your Web* site: Main Web Page ACD/Labs WebLibrarian *

15 Automated System Suitability Certified and Sealed standard solutions in your solvent Run before every Nth sample or at startup Checks Signal / Noise and Line Shape to assure good results. Stops if out of spec.

16 ACD/Labs Structure Confirmation and Databasing Adaptive Experiments Get Results, Save Time 1D Proton >= 1D Proton Acceptance Level HSQC ConfirmedRejected >= AVG(HSQC + 1H1D) Acceptance Level YES NO Copyright © 2006 by Protasis Corporation, All Rights Reserved

17 Automated System Maintenance This is flow Probe Clean Every Nth Sample –1 or 2 cleaning solutions 1 or 2 solvent flushes –Specially designed Acid + Base solution Automated Startup and Shutdown Procedures –1 or 2 Injector and syringe cleans –Probe cleans –Solvent flushes

18 Microgram Samples Make it easier 30 – 300 micrograms of typical small molecules works great If that is all you have, then get it returned. Plenty of source sample, why bother going back to the lab for 100 µ g? Perfect match for analytical (.46cm) scale HPLC peak, scaled-down your purifications Or, take 20 µ L from semi-prep HPLC fraction exchange to d-solvent

19 The Advantages of CapNMR (micro-scale) Scaled-Down Purifications Scrape off a spot into filter. Add DMSO-d6, spin. Collect fractions at analytical scale HPLC Exchange to minimal d-solvent A

20 The Advantages of CapNMR (micro-scale) A Can you spare a few µg? No waiting at the NMR Lab! No return trip!

21 The advantages of going tubeless… No shimming between samples No washing tubes Minimal sample transfer Efficient storage Disposable Economical Incredible Time Savings Copyright © 2006 by Protasis Corporation, All Rights Reserved Plates Make It Easy Would you ever run these in tubes?

22 Current One-Minute NMR Installations 22 Systems Total 17 Varian 5 Bruker 1 Custom Automated Structure Confirmation Systems (VNMR) 2 Turn-Key Automated Structure Confirmation Systems (VNMR/VNMRJ) 3 Walkup Open Access Systems Copyright © 2006 by Protasis Corporation, All Rights Reserved

23 Use Cases Interviewed Feb 9, 2006 & Feb 15, 2007 Scientist A Major Pharmaceutical Open-Access converted to a service. Scientist C Major Pharmaceutical Open-Access Improvement A B Copyright © 2006 by Protasis Corporation, All Rights Reserved C Scientist B Major Pharmaceutical VAST Replacement

24 Use Case: Scientist A A Before One-Minute NMR 3 NMR Systems 5mm Tubes Open-Access Chemists Prepare Samples Chemists Interpret Spectra Actual use: 600 samples / month. Capacity: 1900 samples / month “If utilization gets to 100% there is a hanging.” Copyright © 2006 by Protasis Corporation, All Rights Reserved

25 Use Case: Scientist A 2 One-Minute NMR Discovery Tower Systems + ACD/Labs Automated Structure Confirmation Actual Use: 4000 / month Capacity: / month Structure Verification for Every Sample 1D Verification, 60% Accurate Water Suppression ERETIC Quantitation “Different dynamics now: Verification, used to be done by chemists. It is easy with familiar compounds, but hard when chemistry changes. The demand went way up from Parallel Medicinal Chemistry. It puts NMR back in the game for structure verification.” A Copyright © 2006 by Protasis Corporation, All Rights Reserved

26 Use Case: Scientist A A * 3 Instruments vs. 2 “OMNMR puts NMR back in the game for verification.” Copyright © 2006 by Protasis Corporation, All Rights Reserved

27 Use Case: Scientist A “I just scan the barcode label and click Start.” A Copyright © 2006 by Protasis Corporation, All Rights Reserved

28 Scientist A – Model Compound A

29 Use Case: Scientist B B Before One-Minute NMR: Conventional Flow Injection “It all depends on what kind of data, quant?, dilute?, viscous?, auto shimming?” Capacity: samples / month! Actual Use: 1200 – 1500 samples / month. Copyright © 2006 by Protasis Corporation, All Rights Reserved

30 Use Case: Scientist B Capacity: 5800* samples / month Actual use: 1200 – 2500 samples / month Solvent + Water Suppression Much more robust than (conventional flow NMR). 88 wells/plate, 6 minutes per well, 10 hours per plate, 2.5 plates / day. Using 1/10 th solvent, 1/5 th sample mass More sample goes to screening. OMNMR Enables combinatorial arrays. Used for structure verification and patent backup Happy and looking for continued progress B “OMNMR is much more robust than my old system. I would not want to go back. With the old flow system or Tubes you just wouldn’t do it” * Could run faster 1 entry-level One-Minute NMR System

31 Use Case: Scientist B B Copyright © 2006 by Protasis Corporation, All Rights Reserved

32 Use Case: Scientist B B * Relative values Copyright © 2006 by Protasis Corporation, All Rights Reserved

33 Scientist B: Model Compound B

34 Use Case: Scientist C C Before One-Minute NMR: 5mm Tube Walkup “Chemists are a conservative bunch.” 400 MHz Varian Verification Support Actual Use: All day, 10 minutes / chemist Copyright © 2006 by Protasis Corporation, All Rights Reserved

35 C “We will buy 2 more systems if we can run samples in 5 minutes”. 1.Walkup Plates and Vials 15 min cycle time, Chemists like the system. 2.Excellent data quality 3.Proactive Contact: Administrators like the system but wish it was faster 4.After 1 day of effort, 5 minute cycle times achieved 5.After 2 more days of effort, 1.5 minute cycle times achieved 6.Management approval for new systems, contingent on more effective sample preparation. 7.Filter vials, filter removal tool, and instructions sent, testing underway.

36 One-Minute NMR Economics How does it fit in? NMR provides valuable structure information. Why not have it for every compound? One-Minute NMR puts NMR (vs. MS) back in the game for more samples. Do you want to run plates, and keep open access too? Thinking about a new NMR to expand capacity? Think again! Copyright © 2006 by Protasis Corporation, All Rights Reserved

37 Thanks One-Minute NMR Collaborators Everywhere Scientist A, B, C (You know who you are.) AB Copyright © 2006 by Protasis Corporation, All Rights Reserved

38 Help spread the word! Now NMR is easier and faster One-Minute NMR