The Alfred Mann Foundation Medical Device Incubator Robert ... · 7/23/2019 · Medical Device Incubator May 2019 Alfred Mann. Robert Greenberg MD, PhD. Executive Chairman. Founded

The Alfred Mann FoundationMedical Device Incubator

May 2019

Alfred Mann

Robert Greenberg MD, PhDExecutive Chairman

Founded 1985

AMF Mission

To develop and commercialize innovative solutions for significant unmet medical

conditions

September 2014

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Translational R&D Engine with Commercialization Emphasis

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Corporate Spinouts

• Multiple companies sold for > $7 billion to Medtronic, Boston Scientific, and Sonova

• 4 companies went public (NASDAQ: MNKD, MNMD, EYES, AXNX)

• Companies have revolutionized:– Insulin pumps and glucose sensors (MiniMed)– Cochlear implants (Advanced Bionics)– Spinal cord stimulators (Advanced Bionics)– Visual Prosthetics (Second Sight)– Functional Electric Stimulation (Bioness)– Sacral Nerve Stimulation (Axonics)

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CAPITAL, CAPITAL, CAPITAL

Al Mann COMPANY LIQUIDITY EVENT TRANSACTION VALUE

MiniMed

Advanced Bionics

MRG

Pacesetter Systems

Spectrolab

Heliotek

Advanced Bionics

Acquisition: 2001

Acquisition: 2004

Acquisition: 2001

Acquisition: 1994

Acquisition: 1960

Acquisition: 1960

Acquisition: 2009

$3.7 Billion

$2.7 Billion

$420 Million

$150 Million

Undisclosed

Undisclosed

$489 Million

EnerSys

Flextronics

$30 Million

Undisclosed

Acquisition: 2013

Acquisition: 2012

Alfred E. Mann Companies

Mannkind IPO: 2004 $1.5 Billion

Second Sight $250 millionIPO: 2014

Quallion

Stellar Electronics

AMF Bridges the Valley of Death

ConceiveOf

Idea

ResearchAnd

Development

Product Development

TestingClinical TrialsRegulatory Approval

Commercialization

Confidential

5

AMF Lives Here

Potential Exit Anywhere Along the Continuum

Organizational Snapshot

AMF

~30 Technical

Employees

Idea to Regulatory Approval

State of the Art

Equipment

~50,000 Sq. Ft Facility

2 Clean Rooms

Numerous Labs

Projects

• 3 major development• 1 early stage or minor• 2 clinical studies

People

• Diverse• Educated: MD, PhD

and Masters

IP• ~225 US patents• ~250 foreign

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Confidential

AMF Core Competencies

AMF Competencies

ASIC Design

Packaging

Quality Systems & Regulatory

Submissions

Systems Design

Algorithms

Large to Small

Wireless Comm

Materials Composition

March, 2017

7

Confidential

AMF Seasoned Professionals

AMF Team

MechanicalEngineers

Electrical Engineers

Accounting & HR

Professionals

Quality Engineers & Inspectors

Manufacturing Engineers &Technicians

Clinical & Regulatory

Professionals

Software & Systems

Engineers

March, 2017

8

Confidential

IMES – Implantable Myoelectric Sensor

IMES Device 10

Confidential

IMES – Implantable Myoelectric Sensor

Confidential

Recent Spin-Out Companies

Confidential

12

Axonics Highlights

Confidential

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• State of the Art System to treat overactive bladder• Raised $138M in IPO on NASDAQ – ticker AXNX• Pivotal study complete• Have applied for FDA approval – expected summer 2019

Medallion Therapeutics

March, 2017 Confidential

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• State of the art fully implantable infusion pump

• Smallest pump with numerous advanced safety features

• 75 patient clinical trial completed

Monolythix

March, 2017 Confidential

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• Proprietary polymer that enables fast, accurate and reliable DNA extraction

• Tested and optimal for next generation sequencing• Can be used for point of care diagnostics using a cell

phone as a light source – results in under an hour• Product is inexpensive to manufacture and is

optimized for use in a standard 96 well plate• Several revenue lines can be developed

Bioness

Confidential

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• Company mission to bring technological solutions to neural rehab market

• Developed “best in breed” products including exoskeletal systems and facility based systems

• Stim Router implant system approved and received broad labeling from the FDA following human clinical trial

Confidential

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AMF has an outward-facing incubator to support local early-stage medical device companies.

• Smorgasbord model:• Companies can rent office or lab space• Companies can rent time on equipment• Companies can get personnel support

• (engineering, clinical, regulatory, legal, HR, etc)

• Current status – 2 on-site and 4 virtual incubator companies

Bivacor

– Bivacor• 10 year old Artificial Heart company based in Orange County• Company has unique pump mechanism• AMF partnered on implant development and testing in preparation for First in Man

AMF Equipment

Braze Oven– Heated by electrical resistance

• Temperature uniformity ±1˚C– Maximum process temperature: 1,400˚C– Highest Power Load: 80kW– Average Process Time: 3-4 hours– Chamber Volume: 12”x12”x18”– Modes of Operation: High Vacuum Inert

Gas (such as Argon), Hydrogen– Used For:

• Joining – Brazing, Diffusion bonding and glass to metal sealing

• Heat treating – Annealing and hardening

• Bake-out

5/10/2019 Confidential

21Bldg 33Braze Oven

Vibration Testing Station– Rated output force

• Sine force 500 lbf pk• Random force 350 lbf rms• Shock force 1000 lbf pk, 50 msec pulse

– Displacement (max)• Continuous 1.0” pk-pk• Between stops 1.2” pk-pk

– Velocity (max)• 140 inches per second pk (max)

– Acceleration (max)• 100 g pk, driven• 150 g pk, resonant• 300 g pk, shock pulse

– Frequency range• DC-4.5 kHz, bare table


22Bldg 33 Vibration Testing Station

GE/Phoenix X-ray System– Industrial x-ray system with

computed tomography (CT) capability

– High resolution x-ray gun yields sub-micron image resolution

– Large flat panel solid state detector for low noise, short exposure imaging

– Automatic scanning of the images required for CT 3D volume reconstruction

– Used for product and process development, electronics inspection, and failure analysis


23X-ray GE/Phoenix X-ray System

X-ray Diffraction– A nondestructive analysis tool– Reveals the atomic structure

of the materials, and is based on the elastic scattering of X-rays

– Can determine crystallographic structure, chemical composition, and physical properties of materials and thin films


24Laser Room X-ray Diffraction

Scanning Electron Microscope (SEM)

– Uses a beam of electrons to create a high resolution large depth of field image

– Capable of about 100,000 x magnification

– Captures digital images– EDX (Energy Dispersive X-ray):

a detector system used on the SEM to determine the elemental constituents of materials (determine composition)


25Laser RoomScanning Electron Microscope (SEM)

Laser Welding– Fine temperature control– Controlled glovebox

environment (Argon / Helium)– 3-axis computer controlled

motion– Allows for very precise and

accurately controlled welding of very small components and devices


26Laser Room Laser Welding

Instron Materials Testing System

– Capable of tension, compression, flexure, fatigue, impact, torsion, and hardness testing

– Analysis software– Evaluates the mechanical

properties of materials and components


27Laser Room Instron Materials Testing System

Wire Bonder– Programmable parameters– Attach pure gold wire (.001”

diameter) between miniature electrical components


28Class 10,000 / ISO 7 CleanroomWire Bonder

Miniature Coil Winding– Uses .001” diameter magnetic

wire– Capable of accurately counting

the precise number of turns required

– Winds miniature coil


29Class 10,000 / ISO 7 Cleanroom Miniature Coil Winding

Silicone Molding– Transfer molding press used

to form parts in a mold– Can be used for implantable

biocompatible components


30Class 10,000 / ISO 7 Cleanroom Silicone Molding

Packaging– Components and/or devices

are placed inside sterilization pouches, then pouches are heat sealed

– All sealed pouches are thoroughly inspected prior to sterilization


31Class 10,000 / ISO 7 Cleanroom Packaging

Belco Tray Sealer– Programmable parameters

• Time• Temperature• Pressure

– Medical tray sealer for a variety of inner and outer trays

– Provides consistent quality seals


32Class 10,000 / ISO 7 CleanroomBelco Tray Sealer


33Prototype Machine ShopHAAS CNC Machining Center

HAAS CNC Machining Center– Completely computer

controlled 4-axis– Capable of translating 3D CAD

designs into tool cutting paths to machine exact copies

– Automated tool changing ability

HAAS CNC Lathe– Exclusively used for

fabricating round parts– Live tooling for special

machining applications– Capable of translating 3D CAD

designs into tool cutting paths to machine exact copies


34Prototype Machine Shop HAAS CNC Lathe

Vertical Mill– Manual milling machine with

x-y programmability– Digital read-out for x and y– Capable of holding tight

tolerances


35Prototype Machine Shop Vertical Mill

Toolroom Lathe– Precision lathe– Capable of holding tight

tolerances– Digital read-out for x and y– Microscope for machining

small parts


36Prototype Machine Shop Toolroom Lathe

Optical Comparator– Projects a high magnification

shadow of a part profile onto a screen allowing precision measurement

– Capable of measuring x-y– A clear pattern overlay on the

screen allows comparison with a known part profile


37Prototype Machine Shop Optical Comparator

Materials– Diversified inventory of

specialty alloy steels and plastics

– Implant grade alloys such as 316l, 304l Titanium 6-4

– Specialty plastics (polymers) such as Teflon, Pomalux®, semitron, Delrin®, etc.


38Prototype Machine Shop Materials


39Manufacturing Lab Laser Soldering

Laser Soldering– Provides precise targeting– Fine temperature control– Controlled environment

(argon)

Dicing– Diamond saw cutting of

microcircuits– Precise dimensional control– Gentle action to prevent

damage


40Manufacturing Lab Dicing

Microassembly– Requires high degree of

training and expertise– Most work performed under

a microscope• Soldering• Bonding• Component assembly


41Manufacturing Lab Microassembly

Electronic Testing– Both manual and automated

testing– Probe station testing– Dedicated test stations for

various devices– Testing performed on both

in-process and final assemblies


42Manufacturing Lab Electronic Testing

Sterilization (Autoclave)– Moist heat sterilization– Programmable time and

temperature


43Manufacturing LabSteam (Autoclave) Sterilization

Helium Leak Test – Verify hermeticity of sealed

device– Capable of detecting leakage

rates of 10-11cc/sec


44Manufacturing Lab Helium Leak Test


45Quality Control Receiving Inspection

Receiving Inspection– First Article inspections– Inspection of received materials,

Work-In-Process materials, completed assemblies, and Finished Goods

– Off the shelf and custom tooling for precision inspection

– Verify appropriate traceability documentation requirements are met

– Track equipment calibration

Precision Microscope Station– High magnification measuring– Capable of high tolerance

measurements– Captures high resolution

digital images– Network connected


46Quality Control SmartScope

High Density Storage System– Optimizes space in order to

maximize storage– Quick access– Lockable and secure– Able to easily and securely

separate groups of materials as needed

– Software based inventory control


47Stock Room High Density Storage System

Controlled Storage– Sealed Nitrogen cabinets– Maintains a dry, low-oxygen

environment for critical components


48Stock Room Controlled Storage

ROBERT GREENBERG MD, PHDEXECUTIVE CHAIRMAN

[email protected]

Confidential

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Documents

The Alfred Mann Foundation Medical Device Incubator Robert ... · 7/23/2019 · Medical Device Incubator May 2019 Alfred Mann. Robert Greenberg MD, PhD. Executive Chairman. Founded