UP Philippine Genome Center Economic Opportunities In Genomics My 20- plus years of Commercializing Biotech products: What does it take? Gonzalo Serafica, PhD ChE November 12, 2016

One Engineer’s Story Xylos – Biomaterial Product Development RPI Biochemical Engineering MS and PhD Downstream Bioprocessing - 1989-1992 Biopolymer Production - 1993-96 Xylos – Biomaterial Product Development Topical Medical Device focus 1996-2003 Permanent Implants 2003-2012 Philippine expedition 2013-present Balik Scientist, UP, DLSU, USAID STRIDE Technology Commercialization and IP PRIVATE AND CONFIDENTIAL

Chronology of Research Activities RPI - Affinity Membranes (1989-92) Amicon- Millipore in Boston, MA (‘93) RPI- Bioreactor (1994-1996) Rotating disk bioreactor 7 patents Xylos First Product (1996-2003) Artificial skin and wound dressings Xylos Permanent Implants (2003- 2012) Dura substitute neurosurgical implant PRIVATE AND CONFIDENTIAL

Membrane Bioseparations- 1989-1993 How my commercialization path got started? Membrane Bioseparations- 1989-1993 Nata de Coco boom of 1993 in the Philippines Focused on biopolymer production optimization Filed 1st Patent in 1995 in U.S. granted in 1999 PRIVATE AND CONFIDENTIAL

Microbial Cellulose Technology 1 micron A. xylinum Active Culture Cellulose Fiber (1-10 nanometers width) Top View Sample – base material Properties: Chemically identical to plant cellulose, but structurally unique Cellulose nano-fibrils Optimized cellulose producers Aerobic bacterium leads to laminar structure Branched polymer structure as organisms divide Benefits: No impurities (lignin etc.) High surface area Interpenetrating network of highly crystalline branched fibers Isotropic strength Acetobacter xylinum Biocellulose Full Pellicle PRIVATE AND CONFIDENTIAL

Initial Technical Challenges Shift from research to product development Expand knowledge of potential applications Identify the first product and its advantages Complete regulatory requirements Develop clinical experience to help marketing PRIVATE AND CONFIDENTIAL

Company Start-up Challenges Recruiting early stakeholders- RPI Raising the first venture financing Completing management team Identifying path to market - marketing partner and clinical support PRIVATE AND CONFIDENTIAL

Milestones for Industry Funding 1998 Finish Wound Dressing development Biocompatibility testing completed FDA application filed/cleared Successful animal testing completed Clinical evaluation initiated IP position expanded with J&J patents Real and perceived shortfalls of current materials PRIVATE AND CONFIDENTIAL

Engineer Founder’s Changing Roles Technology Pitch Competitive advantage Regulatory Clearance Pre-clinical and Clinical testing focus on best application Providing marketing support PRIVATE AND CONFIDENTIAL

First Product Launch 2003 5 year to launch and 3 partnerships Scaled up Manufacturing and CE mark Expanded multi-center clinical testing Second FDA product : antimicrobial dressing PRIVATE AND CONFIDENTIAL

Company’s Vision Eliminating the risks, complications and limitations associated with current materials Xylos biomaterial Unique structure Isotropic strength of a non-woven Unique fluid handling and tissue ingrowth properties of a multi-layer lamellar structure Can be bioengineered to deliver specific and precise surgeon-defined performance characteristics. Non-human, non-animal, non-petrochemical vs. PRIVATE AND CONFIDENTIAL

Enabling Technologies Expand Range of Product Applications Enabling Technologies Core biomaterial Wound Care Neurosurgical Musculo- skeletal Abdom / Ob-Gyn Products opportunities virtually limitless in a host of fields of use Cardio- thoracic Plastic / Reconstr. PRIVATE AND CONFIDENTIAL

Technology Focus Xylos Bioengineering Surgeon-Defined Precision Products Physical Those enabling technologies allow us to bioengineer the physical, chemical and composite nature of our core material. Therefore, we can deliver solutions for a diverse range of surgical applications such as: wound care, shoulder repair, gels as bulking agents and membranes to minimize tissue attachment Chemical Composite -13- Private and Confidential 13

Value Proposition :Significant Shortfalls in Competitive Devices Human and Animal Tissue Synthetic Materials Disease transmission concerns Legislative / regulatory restrictions Allergic and immune reactions Material inconsistency Supply limitations High mfg / procurement costs Co-morbidity Limited ability to tailor performance Rejections, inflammation, infections Strength limitations Difficult to handle / conform Difficult to suture / suture retention Adhesions / erosions Real and perceived shortfalls of current materials PRIVATE AND CONFIDENTIAL

First Implantable Product 2003-2012 1st permanent implant (Brain Patch) Completed prototype and safety testing Animal effectiveness testing Search for product Champion 1st Collaborative Research Agreement (CRADA) with a corporate partner PRIVATE AND CONFIDENTIAL

Value Creation after 17 years 7 FDA products cleared/ 2 CE approved Global product use, U.S. and E.U. Received 10 U.S granted patents and 20 IP Asset sale of wound care and neurosurgery More opportunities for other applications PRIVATE AND CONFIDENTIAL

For Platform Technologies - TRIM3 Technology focus/advantage Regulatory Pathway Intellectual Property Market potential Manufacturing Scale up Money – is it worth doing it? ROI (Return on Investment)!!! PRIVATE AND CONFIDENTIAL

Some Lessons Learned Dare to dream One cannot have too many friends You cannot do it all Control is an elusion Failure is not option PRIVATE AND CONFIDENTIAL

What does it take? DRIVE! To Commercialize Technologies … Deliver the promise (proof of concept) Reduce the risks (i.e. regulatory ) Innovate (solutions to real problems) Value creation in every step of the way Effort (sustained as it takes time) PRIVATE AND CONFIDENTIAL

Acknowledgements Early supporters, RPI and NIH-SBIR BC Technology adopters Xylos employees, VC and acquirers UP, DOST, DLSU and USAID Stride group PRIVATE AND CONFIDENTIAL

Thank You!!