Using Nanotechnology to Change Cancer Care

Maryland Technology Day 28 February 2013

The Promise of Cancer Nanomedicines

Deliver potent an6-‐cancer agents directly to the site of disease  Reduced or no toxicity  Improved efficacy Treat cancer as a medical disease first  Dose intravenously prior to surgery  Limited biodistribu6on due to leaky tumor blood vessels  Reduce tumor burden by tumor-‐targeted nanomedicines  Reduce or eliminate sophis6cated surgical procedures  Improve pa6ent outcome Treat cancer as a chronic medical disease  Treat periodically to destroy nascent tumor neovasculature  Suppress metasta6c disease 2

Design of Aurimune (CYT-‐6091):

Water absorbed by PEG-THIOL shields nanoparticle from immune detection 3

Safe, Targeted Delivery: Size MaGers

Too Large for Toxic Side Effects. Aurimune is small enough to safely travel through healthy blood vessels, but too large to pass through blood vessel walls into healthy 6ssues and organs, resul6ng in reduced toxicity.

Small Enough to Exit Tumor Vessels. All solid tumors are fueled by new, “ leaky ” blood vessels that have gaps in their walls. When Aurimune reaches these “ leaky the tumor. ” vessels, the nanopar6cles are small enough to pass through these walls into their target,

Due to its engineered nanometer size and targeted capabiliJes, Aurimune is able to reduce toxicity and increase efficacy.

4

Clinical Grade Aurimune

Current produc6on capacity scaled 10-‐fold from Phase I to Phase II  Process is robust, reproducible and cost effec6ve  Solved manufacturing challenge for a nanomedicine  3-‐year shelf life as a freeze dried product 5

Aurimune Phase I Trial: Clinical ObservaJons

Safe, systemic delivery. dose limi6ng toxicity Delivered 1.2 mg of TNF with no  No Hypotension, the dose-‐limi6ng toxicity associated with TNF use in man  No Serious Adverse Events that were unexpected and related treatment Tumor targeted.  Drug accumula6on at tumor sites Gold par6cles seen in tumors but few if any in healthy 6ssues 6

Electron Micrographs* of a PaJent

’

s Biopsies

Pa6ent diagnosed with inoperable breast cancer   Pa6ent had no prior treatment; samples taken 24h aYer treatment Drug accumulated in tumor, not in healthy breast 6ssue

Healthy Breast

*Magnification = 20,000x 7

Tumor

Montefiore’s Commitment to Nanomedicine

8

The Pipeline: Leveraging PlaWorm’s Flexibility

PlaWorm allows for mulJple cancer treatments for mulJple cancer indicaJons

9

Blueprint of Gold-‐Based, Drug-‐Rescue Nanomedicine

PEG-‐THIOL TNF: A targeted VDA AstraZeneca Proprietary Drug 10

CytImmune Summary

Aurimune will transform current “ medieval ” approaches to cancer treatment Aurimune plus chemotherapies aims to significantly improve responses rates Aurimune is not another “ me too ” drug; it’s a quantum leap forward in cancer Aurimune is the first-‐in-‐a-‐family of nanomedicines CytImmune will create a pipeline of cancer nanomedicines CytImmune’s technology will change the way we treat cancer 11