GlobeImmune’s Scientific Strategy




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Video title: GlobeImmune’s Scientific Strategy
Released on: March 10, 2009. © PharmaVentures Ltd
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GlobeImmune’s CEO, Timothy Rodell, joined PharmaTelevision in San Francisco to talk about the company’s interesting origin and the exciting scientific concepts that it uses to target hepatitis infection and cancer. As a privately owned company coming to the end of a financing round the company is looking to raise money again, but as Dr. Rodell explains it may not necessarily be going to take its lead programmes through Phase III trials alone and could be seeking partners to work with by the end of 2009.
The origin of GlobeImmune.
Fintan Walton:
Hello and welcome to PharmaVentures Business review here in San Francisco. On this show I have Tim Rodellwho is CEO of a company called GlobeImmune which is based in Boulder, Colorado here in the United States. Welcome to the show.
Timothy Rodell:
Thank you.
Fintan Walton:
Tim, GlobeImmuneis a company as I said based in Boulder, Colorado and it has got a interesting origin to the company and in particular the concept that has now developed into the company, so could you tell us about the origin and how that came about?
Timothy Rodell:
Right the company was founded by three scientists and I am not a company founder, was founded by 3 scientists in the University of Colorado who made actually a rather striking and somewhat unexpected observation I mean the observation was that if you take yeast and we're using the same of kind of yeast that are used to brew beer or bake bread and so Brewers used or bakers used, if you immunize an animal an ultimately a human with yeast what you generate, is you generate an immune response to the proteins that are inside the yeast that is strikingly different from other things that you could immunize in a animal or human with, and what is different about it is that the response that you get is a T-cell response it's not an antibody response. Most of things that we use as vaccines are designed to generate antibody responses but the component of the immune system that is most important for the things that we are treating is the T-cell response or cellular immunity and when you immunize with the yeast you get a response that is entirely a T-cell response. That response is directed at any protein that's inside the yeast. So the idea that the founders came up with was to essentially teach the yeast to make a new protein inside them and that protein can be a protein that is expressed in any cell we want to generate a response to. So if you wanna generate an immune response to a virally infected cell then we put a viral protein inside the yeast. If you wanna generate an immune response to a cancer cell, we put a cancerprotein inside the yeast.
Fintan Walton:
Right.
Timothy Rodell:
So that was the idea there, general idea and the platform and everything that we are doing is now based on that.
Concepts in targeting hepatitis infection and cancer.
Fintan Walton:
Right, so once you are able to establish the concept and actually start showing that this could actually happen with some of the proteins, you obviously have to go in and select which proteins you wanted to stop -- say play with?
Timothy Rodell:
Exactly.
Fintan Walton:
So what was the selection process with that? what was the reasoning and logic behind them?
Timothy Rodell:
Well I think you have to ask yourself where is cellular immunity, where are T cells important and the easiest way to answer that question is to look at patients or animals that are deficient in cellular immunity and ask what happens to those patients and what happens to those patients is really three things. If you look at ways that cellular immunity can be imperative, the three points as we see that most frequently are in Aids patients that is sort of an experiment of nature in which T cells are completely knocked out, in patients who are on high dose steroid therapy for a long period of time for Asthma or other inflammatory diseases or in transplant patients, those are the patients who have -- have impaired cellular immunity and three things happen to those patients. The first thing is they get reactivation of intracellular, chronic intracellular infections, so for instance viruses that are living inside us Herpes Viruses, hepatitis virus, tuberculosis which is a Bacterium they get reactivation of those infections. They get very early and precocious cancers unusual tumors much earlier than one would expect, and that get fungal infections which makes sense because I said the T Cells evolved to protect us from fungi. So we were looking at targets that were either intracellular infections, chronic intracellular infections, more cancers amongst the two targets that we selected initially were hepatitis C which is you probably know is a huge problem worldwide, 170 million patients infected probably about 5 million in the US and of those about 50% of those patients can be treated with currently available therapy which is very toxic. So it's a huge problem it's most common cause of liver transplantation, most common cause of primary liver cancer. So hepatitis C was the first infectious disease target we picked and then we picked a series of cancers, solid tumors that are mediated by a mutation in a single protein called Ras and that includes pancreas cancer, lung cancer, colon cancer. So we are doing one program in hepatitis C, and one program that is primarily focused in pancreatic cancer.
Fintan Walton:
Right, so I mean clearly just going back to getting the actual processing cells were Tarmogens, is that correct?
Timothy Rodell:
That's correct.
Fintan Walton:
So Tarmogens, to create a Tarmogens who have to get a certain level of protein expressed inside those yeast cells, is it a critical level which you have to get to?
Timothy Rodell:
Yeah, so what we do is we put the gene for the proteinin other words the DNA that incodes [ph] the protein into the yeast and if you put the gene in under the control of a what molecule called a promoter molecule you can turn on the transcription of that gene and the yeast makes that protein thinking it's making it's own natural protein. Now when we do that we can actually get up to a 10 or even more percent of the total protein in the yeast expressed as that target protein. Then we heat and activate them, we wash them and we boil them. so it's a very simple process. We're essentially making beer it's the same process and the same yeast that's used to make beer.
Fintan Walton:
So the cost of goods is pretty low?
Timothy Rodell:
More we talk in detail about cost of goods but if you think about fermentation process as they are generally very cost effective, yeah.
Fintan Walton:
Yeah, so once you got the levels of proteins expressed to those particularly high levels you're ready to go basically?
Timothy Rodell:
Exactly.
The basis of selection of targets
Fintan Walton:
And now the key issue then obviously is as you say you are selecting specific targets but where those targets selected purely because of their unmet clinical need? What was the basis of the selection of those particular targets?
Timothy Rodell:
Well the disease targets are selected basically because there is a huge unmet medical need as you know in hepatitis C we talk about pancreas cancer it's probably the most deadly cancer around that effects humans so that these are huge problems but there also settings in which we know that cellular immunity is important and to use hepatitis as an example 20% of patients who are acutely infected with hepatitis C will get better on their own, those are the lucky 20%. The other 80% actually generally never know they are infected acutely and they simply turn up 20, 30-years later with that normal liver function tests and the physician takes a history and finds out that the patient was infected 20 or 30- years ago. What we know about the difference between that lucky 20% and the unlucky 80% as what differentiates them is that the 20% of the patient who are able to acutely clear the virus on their own, generally a very broad T Cell response that is directed against multiple different pieces of the proteins that are encoded in the hepatitis infected cell and this has been shown over-and-over again, the patients who become chronically infected the unlucky 80% have a very narrow that is limited to only one or two targets and very low amplitude T cell response to the hepatitisprotein. So we actually know from a cellular immune perspective what differentiates the patients who can acutely clear from the 80% of patients who can't. What we showed initially in animals and we've now shown in humans is when we immunize patient with the yeast that contains the hepatitisproteinwhat we do is we actually convert that narrow attenuated T cell response in the chronically infected patients to one that is indistinguishable from the response you see in the 20% of the patient who acutely clear the virus. And that's associated with improvements in liver function, it's associated with reduction and circulating viral load. So we all already know that cellular immunity is important, we know that 50% of patients treated with conventional therapy are unable to clear. So the question that we asked in our current Phase II study that we are now getting data from, is what happens if we take that therapy that is effective in only 50% of patients and, and super impose on that an augmented T cell response like the response you see in patients who are able to clear this spontaneously. And in the early data that we are seeing now that are coming out of this phase II study the patients who receive our therapy, GI-5005 combined with a standard of care have a higher response rate in terms of reductions in viral load at 4 weeks and I will soon get an update at 12 weeks. so the hypothesis that making these patients who are unsuccessful look from an immune perspective more like the successful patients will improve the clearance of virus we've general -- we've demonstrated in this trial.
Partnering and raising funds.
Fintan Walton:
Amazing and clearly then both you've got these two programs both in Phase II clinical trials. How far you gonna continue with this? you gonna go to Phase III or you gonna start partnering with Phase at the end of Phase II a proof of concept?
Timothy Rodell:
Well it's data driven but I think particular in this kind of financial market the options in terms of financing early stage companies are more limited than they were five-years ago when the markets were in better shape. But more importantly we think that because this platform is as broad as it is that is we have as many potential targets and we can talk about that in a minute. It makes more sense for us to concentrate on generating and validating these products probably through Phase II, we can take them through Phase III but we think it may make sense for us to partner up with the larger pharmaceutical company mostly for the expense of running those later stage clinical trials and those could start as earlier sometime late this year depending on what the data show.
Fintan Walton:
Right, and then clearly you are a private company?
Timothy Rodell:
We are currently private, yes?
Fintan Walton:
You are private and you've raised?
Timothy Rodell:
We've raised a little under $90 million in three private rounds of investment. We have four major corporate investors Lilly, Genentech, Biogen Idec and Celgene [PharmaDeals ID = 33328] in the most recent round. So we've got significant interest and support from the pharmaceutical companies.
Fintan Walton:
And your level of cash at the moment is?
Timothy Rodell:
We are getting near the end of the financing cycle so we sort of looking around the figure of what comes next.
RAS and other potential target programs.
Fintan Walton:
Okay, so we go back to this the other potential targets which you would go for, you clearly got two already, presumably once you get those partners off you will be able to go back to some other additional programs?
Timothy Rodell:
Well I think the idea number one is to validate those programs in as many, well against as many targets as we can and then look at other targets. On the oncology side we didn't talk in detail about the target but the protein that we are targeting is a proteinthat's mutated in 90% of the pancreas cancer.
Fintan Walton:
This is Ras?
Timothy Rodell:
This is Ras. Right. 90% pancreas cancer patients somewhere between 30% and 50% of colon cancer patients, about 25% of lung cancer and about 30% of ovarian cancer as well as the number of leukemias and the thing that is now striking that we now understand about tumors that have these mutations in the Ras protein is that they behave differently than tumors in the same organ system that don't have that mutation in that, they are resistant to conventional chemotherapy, they are resistant through a number of the newer targeted agents, and they are resistant to a number of antibodies . So in fact what we are doing in targeting these mutated Ras protein is really the only advanced program in later stage trials now targeting those particular solid tumors. So the first thing that we are doing is we are expanding from pancreas cancer to look at a number of these other tumors, then we have other programs that are looking at other -- other cancer targets proteins that are either mutated or over expressed in different tumors. On the infectious disease side if you think about it there are huge number of chronic viral infections that potentially would be candidates for this and the one that we are actually looking at with the most interest right now is hepatitis B which is less of a problem in the US now, I mean North America, because there is an effective prophylactic vaccine but worldwide it is one of the biggest, one of the biggest infectious disease and particularly in the far East. So hepatitis B is another potential target and then we are looking at a whole range of other onset.
Fintan Walton:
Tim Rodell, thank you very much for coming on the show and telling us all about GlobeImmune.
Timothy Rodell:
Thank you.
Fintan Walton:
Thank you very much indeed.
Timothy Rodell
President and Chief Executive Officer
Dr. Rodell has been President and Chief Executive Officer of GlobeImmune, Inc. since 2004. From 1999 until 2002, Dr. Rodell was President and Chief Executive Officer of RxKinetix, Inc., a private drug delivery company that was sold to Endo Pharmaceuticals Holdings Inc. From 1996 until 2000, he held a number of positions at OXIS International, Inc., including Chief Technology Officer and President of OXIS International, SA, the company's French subsidiary, and led the Company's IPO on the Nouveau March of the Paris Bourse. From 1985 until 1995, Dr. Rodell was Executive Vice President of Operations and Product Development for Cortech, Inc. where he led all development of three clinical programs and co-led the Company's successful IPO. Dr. Rodell is also a founder of Barofold, Inc., a protein re-folding company. Before moving to industry, Dr. Rodell practiced academic Emergency Medicine, Internal Medicine and Pulmonary and Critical Care Medicine. Dr. Rodell earned his M.D. from the University of North Carolina School of Medicine in 1980. He completed a residency in Internal Medicine and a fellowship in Pulmonary and Critical Care Medicine at the University of Colorado and is board certified in Internal Medicine and Pulmonary Medicine as well as being a Fellow of the American College of Chest Physicians. He completed post-doctoral fellowships in molecular biology and cell biology at the Eleanor Roosevelt Cancer Institute and the Webb Waring Institute respectively.
GlobeImmune
GlobeImmune ,is a privately-held biopharmaceutical company pioneering the discovery, development and manufacturing of potent, targeted molecular immunotherapies called Tarmogens for the treatment of cancer and infectious diseasesGI-5005, GlobeImmune's lead product for the treatment of chronic hepatitis infection, completed enrollment in May 2008 of a multi-center, randomized Phase 2 study. Additionally, GI-4000 for the treatment of Ras-mediated cancers, is currently being evaluated in multiple Phase 2 clinical trials including the treatment of resectable(early) pancreas cancer, NSCLC and locally advanced pancreas cancer. TarmogensTargetedMolecularImmunogens are whole, heat-killed recombinant S. cerevisiae yeast genetically modified to express one or more disease-related protein targets. The whole heat-killed yeast, with the antigen expressed inside, is the - that is administered to the patient. Tarmogens teach the cytotoxic T cells in the patient's immune system to eliminate any cell containing the target proteins expressed in the Tarmogens.