Home Phe Monitor Development Challenge -Advancing the Treatment for PKU- NPKUA SAB Mtg

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1 Home Phe Monitor Development Challenge -Advancing the Treatment for PKU- NPKUA SAB Mtg

2 In October 2013 the NPKUA partnered with InnoCentive, Inc. to challenge the scientific and technical community around the world on the development of a Home Phe Monitor NPKUA & InnoCentive worked together to bring funding from The Cundill Foundation in Toronto to help support the project Together the NPKUA and Cundill Foundation have provided $776,000 to support the Home Phe Monitor Challenge Project NPKUA SAB Mtg

3 Phase I Theoretical Challenge opened to the world on how your technology would meet our specifications. 9 awards of $10K each were made to Solvers selected to move forward to Phase II. Phase II A Three Milestone Challenge: (1) to produced a more detailed Project Plan on how the Solver would demonstrate proof of concept for their technology 8 proposals & 5 awards for $10K each (2) provide test results from bench top prototype with phe spiked blood, 3 awards for $50K each & (3) demonstrate technology with whole blood sample from PKU patients 1 award up to $200K to produce a manufacturable & commercializable prototype. Phase III An erequest for Partners that would manufacture and commercialize the product. NPKUA SAB Mtg

4 The 3 Solvers awarded $50K for the Phase II milestone plus 1 other Solver who continued without the $50K award were invited to Emory for testing with real PKU subjects. Dr. Rani Singh and her team facilitated the testing by bringing in patients from their local metabolic clinic. Normal subjects and PKU subjects with low, mid, and high Phe levels were selected by Dr. Singh s team for venous draw to be used by Solvers and referenced by Plasma Amino Acid Analysis and DBS via Tandem Mass Spectrometry. NPKUA SAB Mtg

5 3 Solvers participated in the study: Conductive Technologies, Inc. (Drs. Musho & Szabo) With electrochemical device using sensor strips Dr. Elain Fu from Oregon State University With powerless paper device using microfluidics and enzymatic colorimetric technology Andrew Dennis, sensor researcher/grad. student With sensor strips and colorimetric device A 4 th Solver, BioTem (Dr. Clarence Deffaud), using lateral flow with custom-made antibody was unable to participate due to lack of progress on device development. NPKUA SAB Mtg

6 CTI phenylalanine meter with a test strip inserted. Meter displaying a 53µM PHE level NPKUA SAB Mtg

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8 methoxyphenazine methosulfate (mpms), is an electron mediator NPKUA SAB Mtg

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11 Lancing device Disposable transfer pipette Running buffer Lateral flow Reader Lateral flow Test General protocol 1-Realizing the blood sample from the fingertip using the lancing device 4- Sample migration for 8 +/- 2 minutes 2-Take 20μL blood from the fingertip using the disposable transfert pipette 5-Read the results of the cassette using the portable Lateral flow reader 3- Add 2 drops of blood sample and running buffer into the lateral flow test NPKUA SAB Mtg

12 Enzyme (phedh & NAD+) instabilities Enzyme lot variations from vendors Calibration concerns due to above issues Hematocrit effect on measurements for some devices (CTI s and Dennis ) Need to rethink specifications for a home phe self monitor vs a true diagnostic device Consequences for FDA approval of a qualitative home self monitoring device vs a quantitative diagnostic device NPKUA SAB Mtg

13 The Final Report from the Emory testing by Dr. Singh s team recommended that none of the 3 devices completely meet the specifications for home monitoring although CTI s device was easiest to use (10-15 sec) and closest to a final product with sensor strip & device fabrications. Solvers were instructed to continue the development of their devices and a follow-up meeting of all Solvers would be held to see how they might collaborate with each other to help improve their devices in order to meet the desired specifications. NPKUA SAB Mtg

14 Solver recommendations going forward: Need further work by enzyme experts to solve the instability and lot variation issues Have renowned metabolic disease clinicians discuss with the FDA the need for a qualitative, self-monitoring device for home use by lay persons vs a quantitative, diagnostic device. Use the $200K to fund the enzyme stability study and to help raise $2-3M to support the product development work that will be necessary to finalize a device for manufacturing that would meet regulatory approval NPKUA SAB Mtg

15 Terence Dunne, Ph.D. at EKF Diagnostics in Dublin, Ireland using colorimetric technology Vamsee Pamula, Ph.D. at Baebies in RTP, NC using microfluidics and detecting phenylpyruvate working with Jerry Vockley at UPMC Rudolf Griss, Ph.D. at Lucentix in Switzerland using luminous technologies Peter Warthoe, Ph.D. at Atonomics in Denmark using trace devices with biomarker modules Marshall Summar, M.D. & Omar Ayyub, Ph.D. at Washington s Children using spectrometric or electrochemical techniques with their own cloned, expressed, and purified GtPheDH from a thermopile bacteria NPKUA SAB Mtg

16 The NPKUA will continue communications with Solvers in the Challenge and those outside the Challenge. Decisions on how to disperse the remaining Challenge funds will be made by the NPKUA Board of Directors in a manner that will hopefully and eventually lead to a successful Home Phe Monitor that meets our specifications.

17 Thomas D. Franklin, Jr., Ph.D. NPKUA Scientific Advisory Board NPKUA SAB Mtg