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Filed Pursuant to Rule 433 Registration Statement 333-208694 March 28, 2016
Advancing therapies through cell signaling
Darrin Uecker, CEO/President + Richard Nuccitelli, Ph.D., CSO
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Information Included In This Presentation
We have filed a Registration Statement on Form S-1 (including a prospectus) (our “Registration Statement”) with the Securities and Exchange Commission (the “SEC”) for the offering to which this communication relates. Before you invest, you should read the prospectus in that Registration Statement, as subsequently amended to date, and other documents that we have filed with the SEC for more complete information about us and this offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, we, our underwriters or any dealer participating in this offering will arrange to send you the prospectus if you request it.
This presentation contains certain forward?looking information about Pulse Biosciences. Forward?looking statements are statements that are not historical facts. Words such as “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,”
“should,” “continue,” “strong,” “up coming,” and similar expressions are intended to identify forward?looking statements. These statements include, but are not limited to, statements regarding our ability to successfully develop and commercialize our products; our ability to expand our long?term business opportunities; plans to conduct future clinical trials; the outcomes of our development activities, and their underlying assumptions; and our future performance.
Forward?looking statements may address the following subjects among others: expected products, applications, customers, technologies and performance, insurance reimbursements, results of clinical studies, success of research and development and our expectations concerning our business strategy.
Forward?looking statements involve inherent risks and uncertainties which could cause actual results to differ materially from those in the forward?looking statements. Investors should review these and other risks inherent in our forward looking statements and our company under the caption “Risk Factors” in our most recently filed Registration Statement. The Company does not undertake, and specifically disclaims any obligation, to update or revise such statements to reflect new circumstances or unanticipated events as they occur.
In this document, we refer to information regarding potential markets for products and other industry data. We believe that all such information has been obtained from reliable sources that are customarily relied upon by companies in our industry. However, we have not independently verified any such information.
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Pulse Biosciences Overview
Novel therapeutic tissue treatment platform
Nanosecond Pulsed Electric Fields (nsPEF) induce a unique cellular response
Addresses multiple potential markets—Tissue Ablation, Oncology, Dermatology/Aesthetics, and Veterinary
Proprietary position in nsPEF technology and IP
Leveraging investment in R&D, IP, and pre-clinical studies from company and partners over the last 15 years.
Dominant IP position with 39 granted patents and 41 pending worldwide.
Capital efficient commercialization strategy
U.S. FDA 510(k) for the platform to perform soft tissue ablation
Pulse generator platform being developed to pursue a number of applications
Potential strategic partnerships for commercial reach
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Unique nsPEF Cellular Effect
Nanosecond pulses applied across a cell create transient nanopores in the cell membrane and organelles.
The nanopores allow Ca2+ to flow + -into the cell, stressing the endoplasmic reticulum, and inducing unique cellular responses.
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Nano-Pulsed Electro-Signaling (NPES)
Modulating the pulses can induce cellular apoptosis, the body’s natural pulse
number
programmed cell death process.
When applied to malignant cells it may
pulse
induce immunogenic apoptosis. amplitude
pulse
Applying the pulses across a volume width
pulse
of tissue may result in complete frequency
tissue ablation. Pulse Modulation Parameters
This novel non-thermal tissue treatment technology is called
Nano-Pulsed Electro-Signaling.
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PulseTxTM – The First Commercial NPES System
Pulse Biosciences is developing the first tunable NPES platform for human clinical use, the PulseTxTM.
Designed to support a wide array of electrodes.
Plan to submit a 510(k) for soft tissue ablation.
Tunable design is based on a novel pulse generator architecture.
PulseTxTM System Design
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PulseTxTM Electrodes
PulseTxTM is designed to support a
Cardiac Clamp
broad array of electrodes.
Relatively small incremental investment in electrode face Electrodes development.
Designs for surface treatments in open surgery and minimally Endoscopic Electrode invasive procedures.
Laparoscopic Electrode
PulseTxTM Electrode Designs
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NPES Applications
Pursuing three significant vertical markets: Tissue Ablation, Oncology, and Dermatology/Aesthetics.
Tissue Ablation
Published data validates the use of Oncology these verticals.
icine Oncology may Dermatology ditional opportunity. Veterinary
Medicine
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NPES for Tissue Ablation
Current ablation technologies use heat or cooling to destroy tissue, causing thermal necrosis and inflammation, resulting in secondary tissue damage.
NPES induces apoptosis, with indicated good healing and little or no scaring.
Ablation zones with NPES depend on the electric field so can be precise and consistent.
NPES treatment times are short—seconds to several minutes.
We believe NPES has demonstrated an ability to induce immunogenic apoptosis, leading to an adaptive immune response against cancer cells.
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Tissue Ablation – Partnership Strategy
Engage strategic partners in cardiac ablation
Partnership opportunities in lung ablation applications
Potential applications include asthma, COPD, and chronic bronchitis
Additional applications in ENT and GI specialties may be pursued through partnerships
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Oncology
Cancer immunotherapy is revolutionizing cancer care
Major biopharma companies investing significantly in internal programs and M&A;
Checkpoint inhibitors have shown good clinical results; and
Leading cancer centers are marketing direct to consumers.
PulseTxTM platform may play an important role
NPES treatment may enable drug-free local tumor control that exposes the immune system to the local tumor antigens;
Potentially overcomes many of the challenges with oncolytic viral vaccines with potentially better results; and
Potentially synergistic with other immunotherapeutics, e.g. checkpoint inhibitors
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Oncology—Immune Response Mechanisms
Oncolytic Viral Immune Response
Tumor Cells Cell Lysis Dendritic Cell
Intratumoral Virus must enter cell Cytotoxic T-cell and replicate (necrosis) Ingestion injection Activation of vaccine
Adaptive
Tumor Antigen
Immune response
NPES In-Situ Vaccine Immune Response
+ NPES Application Dendritic Cell Cytotoxic T-cell
- Cells undergo Ingestion immunogenic Activation apoptosis
CRT on surface Adaptive
Immune response
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Oncology – Immune Response Data
Survival Proportion (Immuno-protection)
N1-S1 Challenge
Survival
Percent NPES treated (n=23)
Days after Initial Injections
NPES Tx
23 Rat liver tumors were ablated, seven weeks later secondary tumors were injected and failed to grow in any of the animals.
Chen et al. Euro J of Cancer 50: 2705 (2014)
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Oncology – Immune Response Data Tumor cells treated in vitro with NPES were used to vaccinate mice against fibrosarcoma tumors. Three weeks post vaccination animals were challenged with a fibrosarcoma cell injection, all NPES vaccinated mice resisted tumor growth unless they were pre-treated with an anti-CD8 antibody. Nuccitelli et al. PLOS One 10(7):e0134364 2015) Pulse Biosciences Confidential 14
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Oncology – Go to market
Demonstrate NPES provides local, drug-free tumor destruction and the potential to elicit a systemic adaptive immune response
Planning to execute a small study using 510(k) cleared system and IDE approval to demonstrate local tumor control and immune response.
The first clinical application may be in the treatment of melanoma.
Several additional applications may follow quickly once NPES is validated in melanoma – head and neck, liver, and lung cancer are all targets.
Partnership opportunities with medtech and biopharma companies
We believe there are a number of oncology medtech companies that will be interested in a partnership.
Biopharma companies involved in immuno-oncology have shown preliminary interest.
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Dermatology/Aesthetics Vertical
Current treatments of freezing, burning or cutting out lesions leads to longer and multiple treatments with disappointing cosmetic results
NPES can provide a compelling treatment option
Apoptosis can result in complete ablation and excellent cosmetic result
Short treatment time and we believe there is potential for single visit treatment
In office treatment that will fit into the office workflow
Immune response potential
Example of Single NPES Treatment
Seborrheic Keratosis
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Dermatology/Aesthetics Vertical
Feasibility demonstrated in human pilot studies using NPES for benign and malignant skin lesions
NPES Basal Cell Carcinoma Pilot Study
Seven of ten lesions completely ablated;
No visible scars in successfully ablated lesions; and
We believe the study demonstrated NPES is safe and can offer a fast and scarless alternative to current standard of care.
NPES Wart Pilot Study
Pilot study of up to 40 patients;
We believe this trial will demonstrate the feasibility of NPES in effectively treating warts; and
May help understand the potential for the treatment of
Example of
Example of
multiple HPV wart indications. Wart Treatment
BCC Treatment
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Dermatology/Aesthetics – Go to Market
Planning for a clinical study in dermatology in 2016 to validate treatment prior to commercialization.
Initial regulatory clearance through the straightforward FDA 510(k) process will be pursued.
We believe the PulseTx will be a good fit in the product portfolios of the large strategics in the dermatology and aesthetics space.
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Veterinary
Commercial Rationale
It has been reported that*,
there are over 70 million pet dogs in the U.S.
cancer is the #1 cause of death in dogs over the age of two
50% of all dogs will acquire cancer, 25% of dogs will die from cancer
Existing therapies tend to negatively impact quality of life
No regulatory clearance needed
May provide a therapy that is easier for the veterinarian to sell to pet owner
Medical Rationale
May provide a simple procedure with minor side-effects as compared to drugs or more significant surgical procedures
Can de-bulk tumor with potentially increased immunogenic activity to other known therapies
*U.S. Pet (Dog and Cat) Population Fact Sheet, American Humane Association, 2012
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Veterinary – Go to Market
Plan to execute studies at major veterinary medicine center(s) to validate scientific thesis
Plan to engage with high volume veterinary oncologists to perform commercial oriented studies
Plan to engage large veterinary chains to assess market feasibility
Potentially partner with large veterinary device or oncology companies
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Intellectual Property
We believe our NPES IP position enables value creation based on the potential for multiple medical indications and multiple business models that can be pursued.
Patent Portfolio
39 issued worldwide
41 pending worldwide
Current patents and patent applications describe
Use of NPES to induce cell apoptosis or cell death
NPES pulse generators, electrodes, and indications
Use of NPES to induce an immune response
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Commercialization Strategy
Develop the first tunable NPES platform, PulseTxTM, to support an array of electrodes.
File for a 510(k) clearance of the PulseTxTM System for soft tissue.
Pilot studies and partnering pre-510(k) clearance.
Pursue partnerships in applications where strategics have domain expertise and an established distribution channel.
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Commercialization Priorities
Focus on applications/indications that require little to no clinical studies
Focus on applications where reimbursement is not critical (eg. aesthetics and veterinary)
Focus on applications where there are multiple partnering opportunities and where our technology could add significant value
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Pulse Biosciences Management Team
Darrin Uecker, President/CEO
20+ years medical device experience
COO of Auxogyn, CEO/President of Gynesonics, CTO of RITA Medical
Experience in Surgical Robotics, Ablation, Women’s Health
Rich Nuccitelli, Ph.D. – Chief Science Officer
Over 35 years experience in biophysics, bioelectrics and medical devices
Over 120 published scientific papers and four books
Past President of the Bioelectromagnetics Society
Brian Dow, CFO
Experienced MedTech CFO and finance executive, in public and private companies.
Dave Danitz, VP of Engineering
15 years medical device R&D product development experience
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Pulse Biosciences Board of Directors
Darrin Uecker, President/CEO, Director
Robert Levande, Chairman (non-Executive)
26 years Pfizer Medical Device Group, various senior management roles
Senior Managing Director at MDB Capital Group
Former Director Orthovita (NASDAQ)
Co-Founder of VirnetX (NYSE MKT)
Thierry Thaure, Director
CEO Cephea
Former CEO Endogastric solutions
Former SVP Accuray
Mitch Levinson, Director
Founder & CEO Cerebrotech
Founder & Former CEO Zeltiq
Robert Greenberg, MD, Ph.D., Director
Co-Founder of Second Sight Medical Products
Co-managed the Alfred E. Mann Foundation
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IPO Overview
5,000,000 shares at $4.00 per share
7.5 million shares outstanding pre-offering, 12.5 million post-offering
Pre-money valuation approximately $30 million; post-money approximately $50 million
Requirement to raise future capital via rights offerings to existing shareholders until company is profitable or shares reach $12 per share
Timing of offering – late April early May
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Pulse Biosciences
Broad platform technology with a dominant IP position;
Experienced team capable of developing and commercializing the technology platform;
A straightforward 510(k) path based on predicate ablation systems;
A number of significant applications to pursue either independently or through partnerships;
Capital efficient value creation plan; and
Multiple value inflection milestones—clinical data, partnership deals, PulseTx sales.
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Advancing therapies through cell signaling
[ 849 Mitten Road + Suite 104 + Burlingame, California 94010 + Tel: 650.697.3939 ]