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It limits tPA and glutamate mediated neurotoxicity, by blocking the binding of tPA to NMDA receptors, providing neuroprotecon PamBio’s drug product in development is an inacve recombinant mutant-tPA protein. Its S481A amino-acid substuon renders the protein catalycally inacve but maintains its structure and ability to interact with major components of the fibrinolyc pathway. This therapeuc biomolecule has a dual, anfibrinolyc and neuroprotecve effect: It is the only known anfibrinolyc drug that blocks both tPA and uPA fibrinolysis enzymes’ acvity, enabling treatment in a me- window beyond 3 hours An-bleeding Neuroprotecon The only known anfibrinolyc agent that inhibits both, tPA and uPA enzymes The only known anfibrinolyc agent that increases the an- bleeding treatment me-window beyond 3 hours Minimizing blood toxicity in the brain Stabilizing blood clots (in contrast to creang blood clots) and prevenng bleeding Prevenng NMDA-receptor- mediated excitotoxic neuronal death High degree of similarity to the human tPA protein that minimizes potenal immunogenicity and organ/ssue toxicity High target specificity for reduced side effects High-affinity binding to targets to minimize dose Unique and safe mechanism of acon Short half-life Nave-tPA as andote Mutant-tPA as andote Control Treated An-bleeding effect Mutant-TPA prevents ICH in mice, post cranial head injury (CHI) PamBio’s mutant-tPA drug benefits include Mutant-tPA prevents neuronal degeneraon in piglets, post fluid percussion injury (FPI) Mutant-tPA (tPAS481A) aenuates neurologic deterioraon in mice, post CHI P < 0.0001 Control FPI FPI + tPA-S481A Higazi et. al., JOURNAL OF NEUROTRAUMA, 2012 Higazi et. al., Blood, 2015 Higazi et. al., Blood, 2015 5 3 10 6 15 9 20 12 25 15 30 18 Mean number of degenerang neurons Neurologic severity score CA1 WT Post CHI+Saline + + * * CA3 WT Post CHI+ t PAS481A Neuroprotecon effect Innovang in therapy for acute bleeding condions Pam-Bio develops the only known drug treatment for hemorrhagic stroke

Pambio Brochure 20160526

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Page 1: Pambio Brochure 20160526

It limits tPA and glutamate mediated neurotoxicity, by blocking the binding of tPA to NMDA receptors, providing neuroprotection

PamBio’s drug product in development is an inactive recombinant mutant-tPA protein. Its S481A amino-acid substitution renders the protein catalytically inactive but maintains its structure and ability to interact with major components of the fibrinolytic pathway.

This therapeutic biomolecule has a dual, antifibrinolytic and neuroprotective effect:

It is the only known antifibrinolytic drug that blocks both tPA and uPA fibrinolysis enzymes’ activity, enabling treatment in a time-window beyond 3 hours

Anti-bleeding Neuroprotection

The only known antifibrinolytic agent that inhibits both, tPA and uPA enzymes

The only known antifibrinolytic agent that increases the anti-bleeding treatment time-window beyond 3 hours

Minimizing blood toxicity in the brain

Stabilizing blood clots (in contrast to creating blood clots) and preventing bleeding

Preventing NMDA-receptor-mediated excitotoxic neuronal death

High degree of similarity to the human tPA protein that minimizes potential immunogenicity and organ/tissue toxicity

High target specificity for reduced side effects

High-affinity binding to targets to minimize dose

Unique and safe mechanism of action

Short half-life

Native-tPA as antidote Mutant-tPA as antidote

Control Treated

Anti-bleeding effect

Mutant-TPA prevents ICH in mice, post cranial head injury (CHI)

PamBio’s mutant-tPA drug benefits include

Mutant-tPA prevents neuronal degeneration in piglets, post fluid percussion injury (FPI)

Mutant-tPA (tPAS481A) attenuates neurologic deterioration in mice, post CHI

P < 0.0001

Control FPI FPI + tPA-S481A

Higazi et. al., JOURNAL OF NEUROTRAUMA, 2012 Higazi et. al., Blood, 2015Higazi et. al., Blood, 2015

5 3

10 6

15 9

20 12

25 15

30 18

Mea

n nu

mbe

r of d

egen

erati

ng n

euro

ns

Neu

rolo

gic

seve

rity

scor

e

CA1 WT Post CHI+Saline

+ +

**

CA3 WT Post CHI+ t PAS481A

Neuroprotection effect

Innovating in therapy for acute bleeding conditions

Pam-Bio develops the only known drug treatment

for hemorrhagic stroke

Page 2: Pambio Brochure 20160526

PamBio is an innovative biotechnology company developing the only known drug therapy for the treatment of hemorrhagic stroke (intracranial hemorrhage, ICH)

Innovating in therapy for acute bleeding conditions

The financial annual burden of ICH in the US and the EU is estimated at US$ 43.5 billion

"tPA Mutant in the Treatment of Acute Brain Injury and Neurodegenerative Disorders“, 2009

"Plasminogen Activator Mutants as Anti-Fibrinolytic Agents“, 2014

Inventors: Higazi Abd, Higazi Nuha Inventors: Higazi Abd, Higazi Nuha (Accepted: EP, US, FR, GR, UK, IN SP; National phase: IL, CA) (National phase: US, CN, EP, IN, IL)

Every year, 15 million people worldwide suffer a stroke. Approximately 6 million die and another 5 million are left permanently disabled

Every 5 seconds a stroke patient dies worldwide

This equals

deaths/year worldwidemillion6.7

Amos Ofer, PhD, MBA – CEO Has experience in directing and managing multidisciplinary, scientific and clinical, research teams. Holds a PhD and a MBA from the Tel-Aviv University

Prof. Abd Al-Roof Higazi, MD – Founder & CSO A leading expert in the field of clinical biochemistry and the head of the Division of Laboratories & Department of Clinical Biochemistry

Nuha Higazi, PhD – Co-founder & CTO

Zohar Gendler, CEO-NGT3 VC – Director Former CEO and director of Beta-O2 Technologies.Former CEO of the Technion Entrepreneurial Incubator (TEIC) for a period of 11 years. Led the establishment and investment in more than 40 companies such as Prolor Biotech, Mazor Robotics and ReWalk

Avri Havron, PhD – Director The former CEO of PROLOR biotech inc., which was sold on August 2014 to OPCO for US$ 480M. A veteran in the Israeli biotech industry with extensive experience in drug development

Paul Waymack, MD, DSc – Director An ex-FDA official, with extensive experience in FDA regulation and drug development processes

Noa Shelach, PhD – Director More than 18 years of experience in leading pharmaceuticals and medical devices

Contact Us

Amos Ofer, CEO - [email protected]

PamBio was established on August 2014 by NGT3 VC – a Jewish-Arab incubator located in Nazareth (www.ngt3vc.com); and Hadasit – the Technology transfer company of Hadassah University Hospitals (www.hadasit.co.il)

IP licensed from Hadassah University Hospitals

Visit our pagewww.ngt3vc.com/pambio-innovating

Market and Need

ICH accounts for Many

are left disabled

Death rates after an ICH are 31% at 7 days

and 59% at one year

of all strokes

ICH is the most devastating

form of stroke%10-15

There is no drug treatment for hemorrhagic stroke