“Starving Tumors with a Therapeutic Diet”

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] Brad Power December 7, 2022 “The hypothesis is that you lower an amino acid, and that starves the tumor.” John Chant Meeting Summary Advanced cancer patients are looking for any boost they can get through lifestyle behaviors (e.g., exercise, meditation) or diet to complement their main medical treatments (e.g.

, drugs, radiation, surgery). Food can strengthen their defenses against their cancer (e.g., their immune system) or even possibly attack their cancer cells. Cancer cells are different from normal cells, and there is a search for ways to starve the cancer cells while supporting normal cells.

Filtricine is a biotech startup founded by researchers who came from Stanford to see if they could starve cancer cells with a restricted diet. They are developing a nutrient formulation which attempts to identify and exploit cancer cells’ metabolic vulnerabilities (the chemical processes that produce energy and basic materials needed for survival).

Their diet eliminates some amino acids that cancer cells need but aren’t needed by normal cells. How far along is the Filtricine product? It’s very early days. Filtricine is recruiting patients for an observational trial where they look at how patients respond to their diet.

They use each patient as a control by switching them on and off their treatment (a “crossover trial”) to see how they respond. They have tested about 20 patients so far. A few patients seem to have responded. What are the ideal characteristics of a dietary product that would help cancer patients?

In the discussion which followed, patients shared their views on the ideal characteristics of a dietary product. It should… ●Taste good ●Be healthy ●Be taken for a short time, or intermittently ●Support, not replace treatment ●Be personalized (e.g., medical situation, vegan, other dietary preferences) ●Be easy to transition to ●Meet taste expectations (e.g.

, chicken noodle soup) ●Be supported by scientific evidence ●Be supported by treating physicians For further information about Filtricine or to volunteer to try their diet, please contact John Chant at johnchant@filtricine.com .

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] Meeting Notes SUMMARY KEYWORDS diet, patients, amino acids, cancer, people, food, psa, product, question, therapy, jimmy, oncologis

ing any health care program, treatment, product or other course of action that might affect your health.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] Meeting Notes SUMMARY KEYWORDS diet, patients, amino acids, cancer, people, food, psa, product, question, therapy, jimmy, oncologist, eat, data, tumor, study, lipids, prostate cancer, trial, nutrition SPEAKERS John Chant (62%), Brad Power (13%), Brian McCloskey (6%), Richard Anders (4%), Eric Hall (4%), Kevin Fordney (3%), Ken Anderson (2%), Stephanie Hall (2%), Jim Ward (2%), Jimmy Wang (1%) The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Brad Power (0:04) John Chant and Jimmy Wang are representing Filtricine. This is one in a series of meetings that we've focused on nutrition and diet and how it can impact cancer.

In particular, down in the metabolic pathway, are there certain things that you can eat, or are there any angles on nutrition that could slow cancer progression? That's the focus of our conversation today. We had a previous session from a couple of patients' points of view on experiences they've had on using nutrition and supplements, and we're going to have a couple more as well.

That sets the stage.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] I've been in charge of Filtricine for about two years. My background is very heavily in therapeutics. I met Filtricine about four years ago. I was a friendly adviser and then a consultant. Then they asked me, based on my experience, to take over running the company.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] The whole idea of Filtricine is very simple. It's that cancer cells are different from normal cells, which we all agree. Cancer cells require nutrients, some nutrients in higher amounts than normal cells. That's well established and was better established by Jimmy Wang and Xiyan Li when they were at Stanford University in Mike Snyder's lab.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] First, cancer cells are altered. Second, they require certain nutrients more than our normal cells. And then finally, it turns out a very easy way to reduce levels of those nutrients that cancer cells require is by a formulated diet.

The scheme of our science, and our clinical approach, is to feed cancer patients a formulated diet, lacking certain amino acids. These are non-essential amino acids.

of those nutrients that cancer cells require is by a formulated diet. The scheme of our science, and our clinical approach, is to feed cancer patients a formulated diet, lacking certain amino acids. These are non-essential amino acids. They're amino acids that you don't need in your diet because your normal cells can make them, but cancer cells have a heightened requirement for them.

It's very simple. We feed patients, and we're doing clinical trials and volunteer studies right now, on a diet that lacks these non-essential amino acids. We're looking at the level and velocity of PSA in prostate cancer patients now. I'll show you a couple slides of data that show encouraging results. We think we're seeing an early signal of slowing the rise of PSA. It's early days.

That's our first dietary formula. We've improved the formula a lot through experiments by Xiyan and Jimmy. We think that we can improve the results to a great degree. When I met the company a few years ago and heard about food and cancer as treatment, I'll be honest, I was a little skeptical, with my therapeutics and a pretty scientific background.

But then I thought that the foundations of logic, which I mentioned, are completely correct. If you want to be dismissive of this idea, one would have to conclude that what one eats has nothing to do with what goes on in your body, and what goes on in cancer cells. It's a nutrient limiting, lowering diet.

Again, these are nutrients your body does not need, because they can make them in your normal cells. It's very akin to diabetes, where we know mild diabetes to moderate diabetes can be managed by sugar intake and the diet they have.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] Here's a schematic of the basic scheme. Your diet normally requires about 20 amino acids for making proteins, and there are other supports. The character on the left on an everyday diet receives a full diet of these amino acids.

There are 11 non-essential amino acids, and 9 essential, so about 20 amino acids total in your diet, and some other more minor ones. He is receiving all these and his tumor in this case is fed by asparagine and serine. They're feeding the tumor, and the tumor is growing. But if you make a diet that has asparagine and serine completely removed, then the tumor is starved.

I won't go through all the data. [Note 20 amino acids; I show three for simplicity] This came out of Mike Snyder's Lab at Stanford, and the great work of Jimmy Wang and Xiyan Li. Jimmy's here. I didn't really introduce Jimmy.

Jimmy is a medical doctor, who is our CTO of the company and has worked in the drug development field and cancer field for a long time and the metabolism field for a long time. Is there proof of the concept of reducing amino acid levels in your blood to treat a tumor?

er field for a long time and the metabolism field for a long time. Is there proof of the concept of reducing amino acid levels in your blood to treat a tumor? Based on my background in pharmacology and drug development, a lot of companies have great ideas, but the question is, does it work in people? There's a proof of concept here that really reassured me.

In a type of leukemia, acute lymphoblastic leukemia, there's already a therapy that gets rid of one of the amino acids, asparagine, by injecting an enzyme called asparaginase. (Asparaginase is used to treat acute lymphoblastic leukemia and is being studied in the treatment of some other types of cancer. It is an enzyme taken from the bacterium Escherichia coli.

It breaks down the amino acid asparagine and may block the growth of tumor cells that need asparagine to grow.) There's one example in cancer. It's a recurring theme.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] vast spectrum of different types of cancers would require amino acids. This was very reassuring that the general scheme could work. What's our product? We have a menu of formulated foods that contain all the nutrients you need. It has about 24 or more components.

Though the names may be different, all these foods have the same formula, in that they're lacking non-essential amino acids. This is what patients receive. One reaction we've had is that if this works you're going to have to eat this food for the rest of your life to get the therapeutic benefit. A couple of things.

It is quite clear that intermittent dosing, a period on and a period off, will probably work. And we have very strong evidence to show that eating this food as part of your diet, and not all of your diet, with normal food, is very likely to work. This is early days. The company was started in 2018. We've got the clinic in just a few years.

One thing I've learned in the pharma industry is that you can do a lot of animal studies and what have you, but you want to get to humans as rapidly as possible to see if you have a signal, is the right way to do things. This is preclinical data.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] Here's a study we performed at Stanford University with Alice Fan and Randy Stafford as PIs (principal investigators). It's very simple. We took all prostate cancer patients, only ten in this case, and we asked them to go on our diet for four weeks. Then we measured their PSA. My father had prostate cancer, and then had a prostatectomy. I know more about PSA than I would have known otherwise, just

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] as a scientist. PSA is very critical to monitoring progress of your tumor, especially in more advanced stages, and in guiding therapeutic choices. Of the ten patients, some had a prostatectomy. Some were met

en in this case, and we asked them to go on our diet for four weeks. Then we measured their PSA. My father had prostate cancer, and then had a prostatectomy. I know more about PSA than I would have known otherwise, just

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] as a scientist. PSA is very critical to monitoring progress of your tumor, especially in more advanced stages, and in guiding therapeutic choices. Of the ten patients, some had a prostatectomy. Some were metastatic. Some were localized.

We saw that two or three patients out of the ten in our first attempt at feeding this diet to patients seem to have a diminution of PSA or a slowing of PSA rise. I like to be very cautious about scientific data. We asked Alice Fan, who was the PI and a full time oncologist, whether there was any explanation for this other than our diet having the effect.

The way we ran the trial was on their regular diet then on our diet and then back on their regular diet. Whatever you want to call it, “crossover”, or “ABA”. Here's one patient, patient five. He's continued on the diet much longer than was required at Stanford University. We show here his rise in PSA.

On the left hand side is his rise prior to the study, and then the gray period is when he's on our diet. John Chant (10:53) To personalize this a little bit, he was very compliant. He was metastatic castration sensitive, but for his own personal reasons he chose not to. He wanted to try our diet. We did not see a cure for his cancer.

But during the 20 weeks, the diet, as measured by his PSA, managed to slow his PSA rise and cause a drop in PSA. Then subsequently, it eventually did go up. This is as, unfortunately, we know, quite common with drugs also. We think we understand why it went up. This is our very first study, putting this diet into patients again after just a few years. We consider this very encouraging.

We're very excited and proud of this.

“Starving Tumors with a Therapeutic Diet” (John Chant) [#36] [This patient eventually went on to treatment with Lutentium-177 PSMA; his response is very good so far. He credited out diet with slowing his PSA rise and giving him more time to find this option and to avoid hormone-reduction therapy.] Here's patient nine. Going into the study, his PSA was rising, so called “velocity”.

As soon as he was put on our diet, which we call Tality, his PSA rise stopped, and then his PSA levels tended to go down. This all comes from Jimmy and Xiyan in Mike Snyder's Lab at Stanford. We're caught up in the details day-to-day running this and doing these trials.

This is the first time, to my knowledge, where someone has shown that depleting nutrients in a diet can be used for treating cancer. There is a little bit of data there about intermittent fasting and starvation. But that's sort of a nonspecific effect.