Mark Davis Q&A

MAKING IT PERSONAL: FINDING A NEW WAY TO TREAT CANCER

When Mark Davis, a chemical engineer, found out that his wife, Mary, had cancer, helping her survive devastating chemotherapy treatments became his mission. Her treatments became so unbearable that she pleaded with her husband to find a better way. “You can fix this,” she challenged him, and so began a scientific odyssey that led Davis to create IT-101, a revolutionary cancer drug. Their story – and the story of the first trial patient to use IT-101 – is featured in CURIOUS, a new series from Thirteen/WNET New York premiering this October 11th 2007 on public television (check local listings for premieres in your market). In the following Q&A, Davis discusses the drug he created and the hope it has already brought.

Q. How and why has cancer been so difficult to treat after so many years?

DAVIS: Cancer is really not a single disease – it is really over a 100 different types of diseases.

What I mean by this is that lung cancer is different from breast cancer that is different of other types of cancer. Additionally, cancer is your own cells “gone mad” so the recognition of them from yourself is very difficult. These and other issues make cancer a very difficult disease to treat.

However, the molecular level understanding of cancer is progressing at a very fast pace now and I believe that we will see spectacular advances in the near future as we exploit this new understanding.

Q. Please provide a quick background on how you came to develop IT-101.

DAVIS: This is the Curious PBS story: I am an engineer, so my approach was to ask what are the essential features that would need to be done to create a new cancer therapeutic that could overcome some of the current limitations. While one can never completely answer the question, certain issues could be defined. I then, began to think about how to design a material and system to address those issues. That approach has yielded IT-101 and other new therapeutics that are now coming along behind IT-101. The key was not to take known materials and try to “bandage them up” to make them work, but rather to start from the beginning and build a system that is designed to function appropriately for the specific job.

Q. How does IT-101 differ from traditional cancer treatments? How is it unique?

DAVIS: Again, this is the Curious PBS story: The way I describe it – it is the first de novo designed cancer medicine to reach humans.

Q. Did you have any previous experience with medical or biological research prior to developing IT-101?

DAVIS: Yes. My undergraduate training was in chemical engineering and pre-med. One of my undergraduate research projects was on nerve function. However, as a faculty member, I did not work on this until after Mary contracted breast cancer.

Q. How is your wife doing now?

DAVIS: She is doing fine. At this point, it is the chemo damage that affects her life, e.g., loss of high frequency hearing.

Q. Can you briefly outline and explain the FDA’s clinical trial process and what the different stages are?

DAVIS: Phase I – is it safe and what dose can be given to patients in a safe manner? What are the side effects and are they acceptable? Phase II – first look at how effective it is in a patient population large enough to be able to generate responses that can have statistical significance.

Phase III – pivotal studies with large patient populations to see if the proposed therapy (dose level, dose schedule) provides any advance over current therapies.

Q. Where does the IT-101 trial stand now?

DAVIS: It is finishing the Phase I trial and will be moving into several Phase II trials (Phase I can be for all types of cancer but Phase II has to be in specific cancer types).

Q. Were you surprised at the initial success of the trial?

DAVIS: Yes. Especially at the first dosing showing effects.

Q. Has your research been specific to the kind of cancer your first trial patient, Ray Natha, has?

DAVIS: Ray has metastatic pancreatic cancer. IT-101 is not specific to that cancer. Our research has emphasized the creation of new therapeutics that would be broadly applicable to many types of cancer.

Q. How have the trial results compared in people with other types of cancer? Have they been similar?

DAVIS: Oth er patients have other cancer types. We are seeing effects in other cancer types but Iam not able to provide you specific details.

Q. How did your relationship with City of Hope get established?

DAVIS: It was through Mary being treated there.

Q. How is Ray Natha doing today?

DAVIS: Ray is still being treated on compassionate use. He remains stable!

Q. What happens to patients after a trial concludes? Do they still have access to the treatments?

DAVIS: Thus far, patients who have successfully concluded the six-month trial are placed on more compassionate use.

Q. Where can people go for an opportunity to participate in trials of experimental drugs?

DAVIS: There is a Web site http://clinicaltrials.gov/ that lists all the clinical trials ongoing.

Q. What are your hopes for the future of cancer treatment? Might there one day be a prophylactic approach to treatment, whereby patients can take preventative or maintenance drugs?

DAVIS: As I say, this is my dream – prophylactic use. We are, in fact, working on the concept of maintenance therapy right now. It is the logical step toward ultimately getting to prophylatic use.

DAVIS: Three to seven years.

Q. Have you ever been featured in a documentary like PBS Curious?

DAVIS: No.

Q. Do you think the kind of visibility PBS will bring to you and your work could help with the FDA approval process, and with funding this and other research?

DAVIS: I don’t know about the approval process. My guess would be that it can’t hurt but I am skeptical that it will really help. I definitely hope that it helps is some way though. At this point it could help get patients to fill our trials faster and that could ultimately help the approval process move quicker. However, I am sure many positives that I have not thought about will come out of the PBS show.

Q. What other research are you working on now?

DAVIS: In addition to our work on therapeutics, we are working on creating new materials for moving ions. Why is this important? We are attempting to synthesize materials to make safer and longer-lasting batteries.

Oct 9 2007

News source: Business Wire

Insert Therapeutics, Inc., a majority-owned subsidiary of Arrowhead Research Corporation (NASDAQ: ARWR), announced today that its lead anti-cancer compound, IT-101, will be featured in a public television documentary series produced by Thirteen/WNET New York and the California Institute of Technology (Caltech). IT-101 is an experimental drug now undergoing clinical trials at City of Hope National Medical Center in Duarte, California.

The series, named CURIOUS, consists of two one-hour documentaries that will air on public television beginning this month (check local listings.) Its focus is the research at the California Institute of Technology (Caltech) and the Jet Propulsion Lab (JPL). One of its episodes, titled Survival, chronicles the early research on IT-101 by Dr. Mark Davis, the Founder of Insert Therapeutics and Professor of Chemical Engineering at Caltech. The show also follows the progress of the first patient in the IT-101 clinical trial.

“We are very pleased to see our Founding Scientist, Mark Davis, receive this recognition for his pioneering work in creating nanoparticle therapeutics,” said John Petrovich, Chief Executive Officer of Insert Therapeutics. “The WNET documentary presents a compelling story as it explores in parallel the personal side of the process of scientific invention by Dr. Davis, and the struggles and triumphs of the first patient to undergo experimental treatment with our drug, IT-101.”

IT-101 is a conjugate of Insert’s proprietary drug delivery molecule, Cyclosert(TM), and the potent anti-cancer compound camptothecin. In June 2007, interim data from the Phase 1 study of IT-101 currently underway at City of Hope Cancer Center in Southern California was published in the 2007 American Society for Clinical Oncology (ASCO) Proceedings (Abstract ID 32638). Stable disease was reported in several patients who completed the six-cycle treatment regimen. In the patients studied, IT-101 showed longer half life, lower clearance and lower volume of distribution than seen in patients treated with other camptothecin-based drugs. The study is ongoing and Insert expects to enter Phase II studies later this year or early next year.

The CURIOUS Survival episode is scheduled to air in New York on October 11, Dallas on October 16 and in Los Angeles on November 15 at 9pm, and will be available in other markets beginning in January. Those interested in viewing the documentary should consult local listings for broadcast times or log onto the companion Web site www.thirteen.org/curious. CURIOUS is distributed by American Public Television and funded by TIAA-CREF, Peter & Merle Mullin and Stan & Barbara Rawn.

About Arrowhead Research Corporation

Arrowhead Research Corporation (NASDAQ:ARWR) is a publicly-traded nanotechnology company commercializing new technologies in the areas of life sciences, electronics, and energy. Arrowhead is building value for shareholders through the progress of majority-owned subsidiaries founded on nanotechnologies originally developed at universities. The company works closely with universities to source early stage deals and to generate rights to intellectual property covering promising new nanotechnologies. Currently, Arrowhead has five subsidiaries commercializing nanotech products and applications, including anti-cancer drugs, RNAi therapeutics, fullerene-based anti-oxidants, carbon-based electronics and compound semiconductor materials. For more information about Arrowhead and its subsidiary companies, please visit our website at www.arrowheadresearch.com.

About Insert Therapeutics

Insert Therapeutics, Inc. (www.insertt.com), a majority-owned subsidiary of Arrowhead Research Corporation, is using its proprietary, nano-engineered, polymeric delivery system, Cyclosert(TM), to design, develop and commercialize drug-delivery-enhanced small-molecule therapeutics and nucleic acids. Cyclosert uses cyclodextrins as building blocks to create an entirely new class of biocompatible materials – linear cyclodextrin-containing polymers that are non-toxic and non-immunogenic at therapeutic doses. Insert’s affiliate company, Calando Pharmaceuticals, is using a related system for the systemic delivery of siRNA. The companies are pursuing this goal through internal research and development, and also through collaborations and partnerships with pharmaceutical and biotechnology companies.