Trial Information

Imaging of Residual Prostate Cancer During Prostatectomy Using ProstaFluor®, a Prostate-Specific Membrane Antigen (PSMA)-Targeted Fluorescent Agent FDA Trial

In this 5 year academic-industrial partnership to FDA approval, an experienced team and
partners including Cornell, Vanderbilt, Intuitive Surgical, LI-COR, and Sand Hill Institute,
will move a prostate-targeted fluorescent contrast agent, demonstrated in animals in a prior
project to allow real-time detection of residual tumor, through FDA approval to human use.
The unmet need is that because prostate tumor at the surgical margin is undetectable in real
time, residual tumor at the margin occurs in 30% of all prostatectomies. Such patients have
a significantly higher risk of local recurrence, metastasis, and death, and also require
radiation therapy. In contrast, even patients with extra-prostatic extension of tumors do
better when the margins are made clean of tumor during surgery.

We propose to leverage our experience and our animal-proven agent to synthesize, receive FDA
IND approval on, and Phase I/II test our targeted fluorescent conjugate in a pilot study in
96 human subjects. Our agent is made from a commercial LI-COR fluorescent dye, and a
humanized antibody from Cornell and Millennium Pharmaceuticals (huJ-591). The targeted
antibody tags Prostate-Specific Membrane Antigen (PSMA) which is present on the outside of
all prostate cells of luminal (prostate duct) origin, and was demonstrated in prior funding
to produce 4-12 fold contrast for prostate cells over nearby tissues in animals. The device
will be tested a sites using a fluorescence-sensitive surgery system from Intuitive
Surgical, a $10 billion robotic surgery company.

The PI of this grant has previously developed and commercialized fundamental optical
technologies -- he (1) co-developed the first in vivo luciferase imaging system at Stanford
and co-founded Xenogen, and (2) he developed T-Stat®, the first FDA-approved detection
system for insufficient blood flow to tissue. Other team members have synthesized dye
conjugates for commercial use, and managed antibody-based drug formulation through FDA
approval.

The corporate partners, LiCor (a world-leader in automated sequencing instruments and
reagents using near infrared devices and dyes) and Sand Hill Institute (experienced at
antibody formulation), and Intuitive Surgical, provide proven commercial translational
experience in contrast agents and FDA approval. These groups will formulate and synthesize
the agent, leading to FDA IND filing and human clinical testing. Alternative paths minimize
risks at each stage.

If successful, the commercial dye will be readied for Phase III multi-center trial with a
major surgical tool partner, a costly and required path to market introduction. Major
imaging companies (Siemens, Phillips, GE, and others) also have molecular imaging programs,
into which this contract agent will fit. A successful imaging agent would likely be adopted.
Extensions to ovarian cancer using the folate type II receptor, and other targets, are
envisioned, including use with other targeting antibodies developed by other groups. We
anticipate that this will be among the first of many real-time surgery-targeting optical
contrast agents in human subjects. Areas with immediate application are the detection of
lymphatic spread intraoperatively for prostate cancer, as well as for ovarian cancer using a
Folate. We expect that the market for such a device in cancer could reasonably be in the
hundreds of millions of dollars/year.