SILK technology driven enterprise FIORENZO OMENETTO DAVID KAPLAN SILK LAB - TUFTS UNIVERSITY SI -K a K_J EFTA01130829 Silk is a natural fiber that has been cultivated in Far East Asia for over 5,000 years. The Chinese domesticated Bombyx mori caterpillars, and then harvested their cocoons in order to produce silk fiber to be used in luxurious textiles. As the material gained popularity in Europe and the Middle East, it eventually lent its name to the "Silk Road," the network of trade routes that connected Asia to Europe, arguably making silk the world's first globalized industry. Today, silk is still produced from the cocoons of these insects for use in textiles from haute couture to home decor, parachutes, and even surgical sutures. EFTA01130830 1. raw materials 3. dissolve the silk in a second salt bath Product: a biocompatible solution of pure silk fibroin and water 2. boil with a salt and wash to remove the sericin (glue-like protein described on page 14) 4. remove the silk by dialysis EFTA01130831 USE THE LIQUID SILK AS THE STARTING BLOCK FOR MANUFACTURING a electronics adhesives nanotech bone addition of functional dopants photonics optical fibers 47 I lib I ligaments microfluidics EFTA01130832 STRENGTHS CHALLENGES UNIQUE MATERIAL Extreme versatility of material in formats and function including unusual operating environments and unusual attributes, namely: sustainable material processing in water at room temperature biodegradable "with a clock" edible implantable in the human body microelectronic interfaces optical interfaces RESEARCH EXCELLENCE Premier research group worldwide Resident knowledge base at Tufts Strong links in place to DoD, US and international labs >70 people involved (research faculty, post-doc, PhD students) PERCEIVED VALUE Perception of silk as the next nylonTM or kevlarTM based on the unusual strength and toughness of the natural fiber "an old story" RAPIDLY GROWING COMPETITION Danger of losing competitive edge - Increasing foreign investment, UK, Germany (>25M$ invested in 4 yrs), India, China, Taiwan NEED FOR SCALE UP develop larger volumes of solution develop repeatable batches per application SILKLAB EFTA01130833 STRENGTHS CHALLENGES BEYOND BASIC RESEARCH Large and growing patent portfolio numerous opportunities for translation licensing and starts ups underway BEYOND SCIENCE UN - FAO - sustainable farming no oil/petroleum consumption in fabrication no methane emission from discarding totally reintegrated in environment BEYOND EXPECTATIONS The unusual freedom to define both form and function open unanticipated opportunities computing organs emo-tronics edible technology biotic/abiotic interfaces personal distributed sensing the bio-cloud BROAD PRODUCT SPACE (spans consumer goods, pharma, medical, high-tech opto and electronic) Expensive to maintain/grow IP position DEVELOPMENT RISK perceived as too risky for traditional funding sources "valley of death" for private enterprise FDA approval for hybrid electronic/biomedical and the biomedical spaces SILKLAB EFTA01130834 programmable forms beyond fibers - multiple material forms from the same starting point micro- and nanoparticles sponges and scaffolds films and conformal coatings hydrogels reversible/permanent adhesives blocks composites and fibers and ropes SILK LA B EFTA01130835 programmable functions beyond fibers - silk is a biomaterial thanks to processing and material features it allows unusual combinations of properties IF N inorganic dopants organic dopants controlled degradation edible implantable interfaces photon ics/optoelectron ics/ microelectronics/nanotech SILKLAB EFTA01130836 programmable forms programmable functions The unique combination of attributes enables performance unobtainable with other materials thanks to the near- limitless ability to combine and recombine forms and functions UNIQUE MATERIAL OUTCOMES disruptive technology DEVELOPING GAME-CHANGING APPLICATIONS and BUSINESSES WITH A MATERIAL THAT HAS BEEN VALIDATED WITH COMPELLING PRELIMINARY DATA and PROTOTYPES SILK LA B EFTA01130837 UNIQUE APPLICATION SPACES - BIOLOGICAL STABILIZATION films microneedle arrays particles gels IUI III • fibers function enzymes Vaccines antibiotics monoclonal antibodies hemoglobin therapeutics delivery / recovery of stored components, sensors, pocket drugs, pocket wound control.... Silk materials can entrain and preserve the biological viability of samples at a variety of temperatures (-30 to 60 degC) — the materials can be recuperated by dissolving or consuming the silk used for storage as needed. SILKLAB EFTA01130838 UNIQUE APPLICATION SPACES - NEW MODES TO ENCODE INFORMATION films microneedle arrays particles gels+particles fibers function bioactivated materials metal interfaces nanopatterns holograms digital information delivery / tracking / friend/foe dissolvable information edible certification holograms/kinegrams biological communicators temporary beacons implantable RFIDs tracking friend/foe ID distributed information C9c117KLAB EFTA01130839 UNIQUE APPLICATION SPACES - HUMAN WELFARE AO! I L function films microneedle arrays blocks/tablets gels+particles fibers e-gels bioactivated materials metal interfaces nanopatterns flexible electronics digital information nutraceutical pharmaceutical sensing multipurpose materials edible hardware food and water quality fatigue sensors personalized monitoring spray on wound stasis military construction adhesives clays/on-site molding Credit card pharmacy skin-mounted sensors SILKLAB EFTA01130840 UNIQUE APPLICATION SPACES - MEDICAL films microneedle arrays particles gels+particles fibers functior bioactivated materials metal interfaces nanopatterns holograms digital information delivery / tracking / friend/foe wound stasis drug delivery next gen prosthetics tissue regeneration defect restoration on-surface devices (wound dressings) sub-dermal devices neurological interfaces Soft interfaces bio-integrated sensors C9cII1LAB EFTA01130841 SILK institute NM • Pr:= Government Grants Philantropic Corporate Donations Inifts .§ time SILK INCMATOR Investment $ PRINCIPAL (IP) INVESTORS INVESTIGATORS & key personnel for-profit <6.11" Y% e pity (royalties) Z% equity The institute is owned by the university, scientists, and investors. All members of the institute have vested interest in its success. The institute builds value for the silk incubator which manages the silk IP. The incubator is within the institute and deals as the institute's own TLO The institute builds value for the silk incubator through technological progress. EFTA01130842 SILK INSTITUTE FOR INNOVATION AND NEW TECHNOLOGIES key assumptions : Silklab is the seed institute for innovation — it addresses technological challenges in basic and applied science to generate business and develop a biomaterials based array of startup industries. Silklab interfaces through its leadership with a dedicated technology transfer that liases with industry partners or entrepreneurs maximizing the ROI on the technology. Silklab always owns part of the startup companies that are generated from its technology development. PRINCIPAL INVESTIGATORS & key personnel tim 1 Y% e quity 2 Ps 2 2 1. Q(3 8 2 X SILK B ECHNOLOGY TRANSFE (IP) for-profit Inyel Z% e Government Grants Philantropic Corporate Donations tn--a uity INVESTORS EFTA01130843 SILK HOLDING COMPANY (II) leverage portfolio position and demonstrated prototypes tim PRINCIPAL INVESTIGATORS & key personnel Y% e (Prototype develo skla r.......r u frastructure = uity )ment) I< SILK INCYBATOR (IP) Z. Cr 03 c;".. X in Inve 0 Z% e Y Government Grants Philantropic Corporate Donations tment $ uity NEW INVESTORS additional equity percentage Product 2 University Legacy InvaMiggigig New investment Product N revenues & royalties EFTA01130844 SILK HOLDING COMPANY (III) PRINCIPAL INVESTIGATORS & key personnel t yok (Prototype devel NEW INVESTORS additional equity percentage k silklaV biological stabilizatio n refrigeratio r I IleSJ vaccines SILK INCMATOR (IP) for-profit (royalties) vascular grafts Government Grants Philantropic Corporate Donations ment $ uity INVESTORS cosmetic implants/fill ers Product N EFTA01130845 SILK HOLDING COMPANY (III) silk abr biological stabilizatio n refrigeratio le vascular grafts cosmetic implants/fill ers PEIWIPP s PERSONNEL PERSONNEL management 3 management 3 management 3 PhD/MD 3 PhD/MD 3 PhD/MD 3 technicians 2 technicians 2 technicians 2 clerical 2 clerical 2 clerical 2 10 +5 new hires) 10-15 by yr.3 10-15 by yr.3 titititi EQUIPMEN T 5NT total 25M FO%JIPMFNT 1=.0 leverage common equipment and supplies for other $ 5M/yr product developments and spinouts total 25M Product N EFTA01130846 SILK- TECHNOLOGY TRANSFER AND DEVELOPMENT - BUSINESS OPPORTUNITIE Leverage versatility Develop parallel product lines that use the common biomaterial technology base to diversify and strengthen revenue opportunities Silk a r Product N ID/Security consumer goods pharmaceutical electrolyte security/anti- bracelets tampering (Gatorade) individual pill holograms/RFID- optical silk/filters for sunscreen RFID signature cosmetics (personalized proteiin glitter document security) antibiotic filter edible holographic masks for flu film (food season certification/organic certification, ...) non-toxic toys programmably edible dissolvable books/calendars- holograms nutrition etc. (humidity- holographic cosmetics sensors)- product contamination Sensing food safety glucose sensors (both antenna based and optical) remote environmental sensing (chemical sensing reflective tape) MRSA-hospital acquired infections (business plan +team exist) smart-slides optical sensors/optical assays) stabilization of bio- fluids (blood, saliva, urine) for portable analysis biomedical restoration of soft tissue defects (large) silk mats-wound dressing — bums light-activated antibacterial gel multifunctional sutures ((fiber optic sutures, heating sutures,therasuture) nerve grafts silk orthopedic screws reversible surgical adhesive bone fillers/regeneration Storage Delivery refrigeration free storage of: vaccines tetracyclenes antibodies drugs pharmaceuticals DNA RNA enzymes delivery — enzyme packages for controlled fermentation/ripenin g (food industry?) immobilization and storage of scents and flavors electronics BIO RFID conformal electrodes/abiotic- biotic interfaces organic electronic interface — silk oxides for organic semiconductors implantable/resorbabl e inductive power and resorbable electronics technical edible/implantable compnents temporary RFID tattoos (e.g. children tracking in crowded criaracl EFTA01130847 An argument for a new material platform Biomaterials have been in use for long in the human body to improve body functions and replace damaged tissues. These biodegradable biomaterials have evolved from biomaterials that do not react with the environment and easily dissolve in the body. Advances in technology and the emergence of innovative biomaterial products have enhanced the performance and applications of these biomaterials. Metals and ceramics dominate the biomaterials market. The global market for biomaterials is expected to reach $64.7 billion in 2015 from $25.6 billion in 2008 with a CAGR of 15% from 2010 to 2015. Biomaterial markets holds significant opportunity for innovators; an extensive research is required to develop new and improved products at competitive prices. With increase in the percentage of aging population worldwide, the number of individuals suffering from physical disability is also increasing. Baby boomers born between 1946 and 1964 are the major consumers of the biomaterial products. Besides, more than 20% of the global population in 2050 is expected to be over 60 years and this segment (of the population) will be significantly high in developing countries. This increase in the aging population will drive the demand for biomaterial products. EFTA01130848