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Perpectives of

the Scientific

Founder

Frederico Costa, MD Founder

August 8th 2017

Perspectives of the Scientific Founder

Disclosure

- Dr Costa is founder of Ipsum Medical. - Ipsum Medical is a Biotech. LLC in NH, USA. - Dr Costa funded all clinical studies. - Dr Costa is the inventor and the assignee for US and PCT patents.


Lord Russell

Bertrand Arthur William Russell (1872 – 1970) was a British philosopher, logician, mathematician, historian, writer, social critic, political activist and Nobel laureate

When you are studying any matter, ask yourself only: what are the facts? What is the truth they bear out? Never let you be diverted by what you believe or how your beliefs would benefit you. Look only at what are the facts.

Global cancer incidence

World Cancer Research Fund

• There were an estimated 14.1 million cancer cases around the world in 2012.

• This estimate is expected to increase to 24 million around the world by 2035.

• In US there was an estimated 1.7 million new cases for 2017.

http://www.wcrf.org access on August 4,2017 Siegel et al Ca Cancer J Clin (2017) 67: 7-30 Ferlay eta l. Int. J. Cancer (2010) 127: 2893-2917

The motivation


59 yo postmenopausal female with ER/PR positive, Her-2 negative breast cancer 7/2005 - Complete clinical response after 4 weeks of treatment. Durable response for 11 months.

Barbault & Costa et al., J Exp Clin Cancer Res. (2009) 28:1-10

Low energy radiofrequency

electromagnetic field


Cancer-specific modulation frequencies from 100 Hz to 21 kHz

27.12 11


Human body

Specific Absorvation Ratio

Perspectives of the Scientific Founder Niels Kuster, the Foundation for Research on Information Technologies in Society (IT’Is), Zurich

Discovery of tumor-specific

frequencies

Perspectives of the Scientific Founder Barbault & Costa et al., J Exp Clin Cancer Res. (2009) 28:1-10

Tumor-specific frequencies

by tumor type


Example: 1873.477 Hz, 2221.323 Hz, 6350.333 Hz and 10456.383 Hz

• Scanning of AM RF EMF* at frequencies ranging from 100 to 114,000 Hz. • Selected frequencies eliciting the best pulse alteration responses.

• Pulse alterations by pulse palpation.


Antitumoral effect in

patients with cancer

Outpatient treatment


n %

Coaxial cable

Mouthpiece (spoon)

Emitting device

- Toxicity - G1 somnolence

Study demographics


• Liver cancer is the 5th cancer incidence in the world, with 782,000 new cases/year in 2012.

• Liver cancer is the 2nd cause of cancer death in the world, with 750,000 per year.

• Liver cancer has the lowest survival rate with < 10% 5-year survival rate.

• Hepatitis B, hepatitis C viruses and alcohol are most important causes of liver cancer.

• It is associated with poor liver function (cirrhosis) in 85% of the cases.

• 90% of patients are diagnosed with advanced disease and < 50% have treatment option.

• Best systemic treatment will extent median survival by less then 4 month.

Ferlay et al. Int. J. Cancer (2010) 127:2893-2917 Bosch et al. Gastroenterology (2004) 127:S5-S16 Cholankeril et al. World J Hepatol (2017) 9:533-543

Liver cancer statistics

Unmet need

Ieda-Ueno et al. World J Gastroenterol (2017) 23:2651-2659 Zamor et al. J Gastrointestinal Oncol (2017) 8:229-242 Ponziani at al. World J Hepatol (2017) 9: 352-367

Llovet al. N Engl J Med (2008) 359:378-390 Bruix et al. Lancet (2017) 389:56-66 El-Khoueriry et al. Lancet (2017) 389:2492-502

Perspectives of the Scientific Founder Costa, et al. Br J Cancer (2011)105:640-8

Antitumoral effect in patients with

hepatocellular carcinoma



41 patients


AM RF EMF exposure technique

Study demographics

Costa, et al. Br J Cancer (2011)105:640-8




Characteristics of patients with either PR and/or long-term survival in excess of 24 months.

Abbreviations: AFP = a-fetoprotein; BCLC = Barcelona Clinic Liver Cancer; CLIP = Cancer Liver Italian Programme; GI = gastrointestinal; MELD = Model for end-stage liver disease; N/A = not applicable; PR = partial response; SD = stable disease.

Costa, et al. Br J Cancer (2011)105:640-8



Perspectives of the Scientific Founder Costa, et al. Br J Cancer (2011)105:640-8 Bruix et al. J. European Journal of Cancer (2013) 49:3412–3419

Median progression-free survival was

4.4 months (95% CI 2.1 – 5.3). Median overall survival was 6.7 months (95% CI 3.0 – 10.2).

- Objective response was confirmed by three independent radiologists (Brazil and US).

- Partial response by RECIST 1.0

- 75.6% had radiological evidence of progression at the time of enrolment. - Toxicity - G1 somnolence * Tox G3/4 - 67% - Regorafenib, approved drug in child A*

* 10% 54%

*1.4 months

* 7.8 months

Translational research


In vivo studies In vitro studies

Zimmerman & Costa et al. Br J Cancer (2012) 106:307-13

Cell culture chambers

Xenograft chambers

Antitumoral effect demonstration in

cell culture

Perspectives of the Scientific Founder Zimmerman & Costa et al. Br J Cancer (2012) 106:307-13

Antiproliferative effect in cell culture

of immortalised cancer


Disruption of the mitotic spindle in cancer cells.


Well defined mechanism of action

Perspectives of the Scientific Founder www.ipsummedical.com - translational research

• Exposure to low levels radiofrequency electromagnetic fields amplitude

modulated at tumor-specific frequencies.

• Alteration of the IP3/DAG signaling pathway exclusively in cancer cells.

• Inflow of calcium mediated by T-type calcium channels in cancer cells.

• Anti-proliferative and pro-apoptotic effect in cell culture.


http://www.ipsummedical.com

In vivo experiments


NOD scid mice 7x106 cells: HCC, breast and ovarian cancer cell lines derived from patient tumors

Palpable Tumor Formation

Injections 7x106 cells

AM RF EMF Exposure 0.4 W/kg, three one

hour treatments daily

Tumor growth in Xenografts

Subcutaneous injection of Huh7cells

Xenografts treated with HCC-specific

AM RF EMF


Week

Model: Subcutaneous Cellular Xenograft in NOD SCID Mice Cells: Huh7 hepatocellular carcinoma

Tota

l Ch

ange

in T

um

or

Vo

lum

e (Δ

mm

3)

Control n = 4

Treated n = 5

p = 0.0106

1 2 3 4 5 6

Vo

lum

e (m

m3

)

Weeks 1 2 3 4 5 6 7 8 9 10 1 12 1314 15 16 1718

Treated Observation

Only

Each volume is

an average of 3

weekly

measurements

Gimenez & Costa et al, BEMS poster presentation 2015

Subcutaneous injection of HCC cells


AM RF EMF


1 2 3 4 5 6

Control (N = 17) 43.21 55.20 62.93 91.12 99.72 128.78

HCC Treated (N = 20) 50.43 53.50 52.05 60.08 61.24 68.88

0

50

100

150

200

Tu

mo

r V

olu

me

(m

m3

)

p = 0.04

P = 0.019

Control n = 17

Treated n = 20

Gimenez and Costa et al, BEMS poster presentation 2015

Subcutaneous injection of HCC cells


AM RF EMF

Perspectives of the Scientific Founder Gimenez and Costa et al, BEMS poster presentation 2015

HepG2-1

Tumor magnification: 200x Lung Small

intestine Kidney

• Significant antitumoral effect observed in residual tumor.

• No toxic cellular effect in lung, small intestine and kidney tissues.

• AM RF EMF inhibit cell proliferation and has pro-apoptotic effect.

Blackman et al. Br J Cancer (2012) 106(2):241-242

Relevance within the scientific

community

Relevance within the scientific

community

47 citations 74 citations


Costa, personal communication

AM RF EMF exposure initiation

Continuous registration of blood pressure 1

1. Task Force® Monitor (CNSystems Medizintechnik GmbH, version 2.2.12.0, Austria)


Hemodynamic alteration by

exposure to tumor-specific

frequencies


Pulse wave


Ipsum Medical – Research platform

Artificial Intelligence

Computer

Device

(emitter)

Patient

Hemodynamic

monitor

Ipsum Medical Integrated research platform


Hemodynamic monitoring during

exposure to tumor-specific

frequencies

1- Task Force® Monitor 2- RF generator 3,5 - Arm cuffs 4- Finger cuff

Hemodynamic parameters recorded beat-to-beat

Costa et al, BEMS poster presentation 2015


Prospective study

Hemodynamic monitoring during

exposure to tumor-specific frequencies

Double-blind exposure: • HCC-specific frequencies • Breast cancer-specific frequencies • Random-chosen frequencies

3 sequences of exposure: • Random – Breast – HCC • Random – HCC – Breast • HCC – Random – Breast

Exposure: 194 frequencies – 10 min Emitter: OncoBionic P1 device

• Patients – (40): - with advanced cancer (HCC or Breast) • Controls – (41): - no active disease in the last 6 m

Costa et al, BEMS poster presentation 2015


Electrical activity of the Heart

R –R interval (RRI)


Heart rate variability

Inter-patient and intra-patient variability

European Heart Journal (1996) 17, 354–381 Voss et al. Cardiovascular Research 31 ( 1996) 419-433

Inter-patient variability Intra-patient variability

HR variability analysis by spectroscopy

Frequency power

Perspectives of the Scientific Founder Chang et al. Med Biol Eng Comput (2014) 52:343-351

HRV analysis in Medicine

• Identification of risk population

• Ischemic events

• Heart death

• Hypoxia in fetus during labor

• DM damage

• Etc

• EKG analysis – RR interval variability

• Non-invasive

• Highly accurate

• EKG 10 min to 24h holter

• EKG 10 s short intervals

Billman. Frontiers Physc (2011) 2:1-13


Interaction between different systems

Autonomic regulation


Heart rate variability and

the scientific community


Artificial Intelligence procedure

Selection of known attributes and dependent new attributes

Coordinate transformation based on relevant component analysis

Optimize common “metrics”

Cluster analyses for characteristics identification

New discriminating attributes for pattern identification

Deep machine learning with cutoff refining


Linear regression’s library

tumor-specific frequencies

Women - Breast cancer Men – Hepatocellular carcinoma

HHCC = 0.2938 + 0.5067x

MMama = 0.4753 + 0.5020 x

MMama = 0.4753 + 0.5020 x

Diagnostic frequencies Disease

Diagnostic Frequencies Disease

D1

Confirm D1


D1

Confirm D1

Possible D1


D1

Confirm D1

Diagnostic frequencies Disease

D1

Confirm D1


D1

Confirm D1


D1

Confirm D1

D2

Confirm D2


D1

Confirm D1

D2

Confirm D2

Possible healthy

Unsupervised analysis 66 patients construction+ 60 patients validation (Breast cancer – HCC – Healthy controls) - Sensitivity 100% - Specificity 86%

Treatment Frequencies Disease

D1

D2 Possible healthy


Deep machine learning

Evolutionary (spiral based)

Approach to solution.

Knowledge base

Artificial Intelligence

Unsupervised clustering

Periods

Periods

Periods

Pattern identification

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Periods

Deep machine learning

Wiked problem: “The problem is not understood until after the formulation of a solution”.

Conklin at el. Building Shared Understanding, USA 2005.


Screening for Liver cancer

Unmet need

Bruix et al. Hepatology (2005) 42:1208-1236 El-Serag et al. Therap Adv Gastroenterol. (2011) 4:5-10

• High risk population.

• Annual ultrasound combined with biannual AFP.

• 60% sensitivity and 85% specificity.

• US$19,000/quality-adjusted life-year.

• Early disease: 40-70% 5-year survival rate.

Ipsum Medical

Treatment

solution

Diagnostic

solution

Electromagnetic fields

Frequency modulation

Ipsum Medical

Service provider


Ipsum Medical Commercial solution

Knowledge

base (A.I.)

Portable device

(emitter and

receiver)

Patient

(Secure wireless connection)

AM RF EMF EKG Products 1- Outpatient treatment for hepatocellular carcinoma.

2- Searching for tumor-specific frequencies (library).

3- Cancer diagnosis and patient’s treatment follow-up.


Validation study

Approved for immediate

patient accrual

Ipsum Medical

Where we stand


• Legal constitution of Ipsum Medical LLC (mid August/2017).

• ISO 13485 compliance procedures (end of August/2017).

• Portable Ipsum device for testing – risk 2A (validation trial) (end of August/2017).

• Clinical Evaluation Report in accordance with Directive 93/42/EEC

and MEDDEV 2.7.1 Rev 4 (September/2017).

• CE mark process planned for treatment and diagnosis of hepatocellular carcinoma

(October-November/2017).

• Start medical device production for commercial use (January/2018).

Ipsum Medical

SOPs

Medical device

Production

Operation

Quality

assurance

Clinical

development

Oncology

Cardiology

Others

Management

Office US

Office EU

Office BR

Distribution

Knowledge base

R&D

Consultant 1

R&D

Consultant 2

R&D

Consultant 3

R&D

….

R&D

Client

diagnosis

Client

treatment


Ipsum Medical

Structure

CEO

Business Planning

Hardware Design &

Physics

Regulatory Affairs Research &

Development

Software design

& A.I.

Quality Assurance

Operations Business

Development

CFO

Project Mgr

Medical Solution

& Consultant(s)

Business Strategy

Intelectual property

&

protection

Administratio

n Board

Communication

Marketing


Ipsum Medical

• Scientifically accurate

• Naturally innovative

• Practical

• Hope

Perspectives of the Scientific Founder www.ipsummedical.com

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