Spyker Biomaterials

Novel spider silk materials for clinical use.

Clinical Problem:

• Pelvic Organ Prolapse• Descent of bladder, uterus

or rectum below its normal anatomical level.

• Major Risk factors

Gravity

Gravidity

Obesity

Multiple pregnancies

Racial factors.

Clinical Problem:Stages of prolapse

Epidemiology:

• Variable data – Loss of utero-vaginal support seen in 43-76%.• Women’s Health Initiative

– 41% of women over 50 show some amount of POP.– 34% had a cystocele, 19% rectocele and 14% uterine prolapse– Lifetime risk of undergoing surgery for SUI or POP is 11.1%– More than 300,000 procedures performed in the US annually for

POP.– About 13% of patients who undergo a surgery will require a repeat

procedure in 5 years.

• NCHS lists genital prolapse as one of the 3 most common causes for hysterectomy in women.

Clinical Problem:

• Urinary SymptomsIncontinence

Frequency

Urgency

• Vaginal SymptomsDyspareunia

Spotting

Discomfort

• Bowel SymptomsConstipation

Incontinence

Loss of Sensation

Current Solutions:

• Non SurgicalPelvic Floor Exercises

Vaginal Creams

Vaginal Pessaries

• Surgical Fascia tightening

Introducing Slings and Meshes

Hysterectomy Abdominal Vaginal

Current Solutions:

• Non SurgicalPelvic Floor Exercises

Vaginal Creams

Vaginal Pessaries

• Surgical Fascia tightening

Introducing Slings and Meshes

Hysterectomy Abdominal Vaginal

Standard of Care ( slings and meshes)

• Autografts• Allografts(cadaver)• Xenografts• Synthetic (non absorbable)

– Nanoporous (<1 micron)– Macroporous (<10 micron)– Macroporous (<10 micron)– Macroporous ( >75 micron)

• Materials– Polypropylene (LWPP v/s HWPP)– Polyester– PTFE– PLGA

Market:• Most major medical

device companies in this market.

• Mesh prices range from $250 - $1000.

• DRG Code reimbursement- $5800 to $17,280.

• Over 300,000 surgeries performed every year.

• Billion dollar market.• Higher Pricing –

possible.

Complications

• Biomechanical Reaction:Enzymatic degradation of the filaments leads to loss of mechanical strength.

Complications:

• Host responseInflammation, aggressive macrophage response, excessive fibrosis, contractures and scarring.

Complications:

• Host responseInflammation, aggressive macrophage response, excessive fibrosis, contractures and scarring.

Complications:

• Host responseInflammation, aggressive macrophage response, excessive fibrosis, contractures and scarring.

Side effects:

• Erosion and Extrusion through vaginal wall.

• Vaginal discharge and infections

• Perforation of pelvic organs

• Pelvic pain and dyspareunia

• Incontinence• Scarring• Recurrence of POP

Such a Mess:

• 2001 – FDA clears first surgical mesh for POP.• Late 2000s - 300,000 surgical repairs done every year.• High recurrence rate (6-29%)• Severe complications including erosions.• 2008- FDA issues a Public Health Notification cautioning

patients and physicians of S/E.• Over 100 synthetic meshes in the market.• 2011 – FDA receives over 4000 complaints(2005-10) of SAE.• Warning letter issued. Complications “not rare”.• 2012- First major recall by J&J.• 2015 – About 70,000 women have filed lawsuits.

Current Pelvic Mesh Solutions

Top Characteristics for pelvic mesh:

• Large pore size• Flexibility• High Tensile Strength• Toughness (absorbs energy)• Fibrous capsule formation

Pott et al. PLoS ONE 2012

Our Recommendation

• SF based start-up Spider Sense.

• Creates spider silk for medical applications.

• R&D for past 3 years.• Perfect biomaterial for slings

and meshes.• Future applications like

Ligament and skin scaffolds.• Spider silk already being

commercialized for clothing and other applications.

Dragline Silk

Rising & Johansson, Nature Chemical Biology, May 2015

Other properties• Light weight (1.3 g/cm3)

• Sterilizable, can withstand approximately 250 [12,13].℃

• High supercontraction rate: absorption of water leads to tightening of thread to maintain rigidity.

• Silks have proven high antimicrobial properties, suggesting their use for medical application

• Spider fibers were well-tolerated up to 10 months in regeneration of sheep peripheral nerves in vivo

Subcutaneous Fibrotic Response: Vicryl vs. Trypsin-treated Spider Egg Sac Silk, 4 weeks

Vicryl Spider Silk

*=fibrotic response K Gellnyck et al. J mater Sci. 2008

Fibrotic Response: Silicone Implant vs. Spider protein-coated implant

PH Zeplin et al. Adv. Funct. Mater 2014

Biggest Challenge: Manufacturing and Scale-up

• Spiders are cannibals• Fibers from heterologous hosts require processing.• Failure to duplicate natural mechanical strength• Little known regarding the physiological properties of

spinning glands

Biomimetic Spider Silk Spinning Device

Rising & Johansson, Nature Chemical Biology

Fibrotic Response: Silicone Implant vs. Spider protein-coated implant

Regulatory Pathway:

• Current Meshes are FDA approved.• Silk is FDA approved for many applications.• Seri-silk Scaffold by Serica approved in 2009.

Silk Proteins converted to multifilament fibers

Sericin extracted from fibers Purified fibers assembled into 3D

scaffolds.

Regulatory Pathway:

• Use Seri Scaffold as predicate device.

• Clinical Indication- P.O.P.• Apply for 510(k)

clearance.• Requirements:

• Bench top testing.• Biocompatibility

studies.• In vivo Rabbit studies.

• Estimated time: 12 -18 months.

Thank you