Disclaimer: the author is no longer long shares or options of $GALT, but is considering entering a small position the next month.
Monday, Galectin Therapeutics announced the results of a small preclinical study. You can read about the results from their investor relations website. You can also click here to see my previous take on Galectin Therapeutics. There are definitely some large positives in their brief press release, along with a few questions I'm left with. Hit the jump for my take on what the preclinical trial means.
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GR-MD-02 again shows efficacy
It's always nice to see companies "repeat a positive"; another piece of evidence (in a preclinical trial) demonstrating the efficacy of GR-MD-02 in reducing liver damage and weight in diabetic/obese mice is always welcome. I am somewhat irritated, however, that no description of the type of "diabetic mice" that were used in the study is given, outside of the fact they were induced to become obese with high fat diet. It would have been nice to have some idea of how large these mice were exactly. Additionally, it is always interesting to see these treatments carried out in genetically obese mouse models, as it's easier to see a dramatic, robust change. There is a HUMONGOUS difference between a mouse fed high-fat diet (one standard method of creating a "diabetic" mouse) vs. a genetically obese, diabetic mouse (for instance, animals lacking either leptin (ob/ob) or leptin receptor (db/db) mice). See the pictures for a visual comparison. It's easier to show a significant improvement in the genetic models of obesity, simply because of how massive those animals are compared to their 'normal' sisters and brothers. Regardless, the actual data that were presented looked quite good, considering the changes in markers of liver damage.
Changes in liver size are confounding
It is questionable to me that there were significant differences in liver weight between the two groups (with the GR-MD-02-treated group having smaller livers). The data would have been much more provocative without these changes, as it is possible (if not very likely) that the reduction in liver size or triglyceride content (which was not reported alongside plasma triglyceride content) could be the driver of the actual effects of the drug. Although these animals were induced to become obese by a high fat diet, it is likely (in my experience with these models) that during the course of treatment with GR-MD-02, the high fat diet was continued to be fed (this is not specified in the release). It is therefor possible that GR-MD-02 was simply reducing the expansion liver. I'm really not sure, as it's not clear from the press release, but some more details would have been welcome in order to make an informed analysis. It would be beneficial, of course, if GR-MD-02 was also reducing the size of livers in patients, but in these preclinical studies I always prefer to see "cleanliness" rather than broad-stroke effects. Regardless, these aren't big confounding factors, and I still find the data compelling enough to reinforce my belief in the ultimate success of GR-MD-02.
GR-MD-02 is efficacious, orally
To me, this is the biggest revelation of this study. The current treatment regimen in GALT's phase I trial includes IV dosing of GR-MD-02, which is not ideal; it is harder to get a sustained effect of the drug, and requires frequent visits to a physician to receive the injections, costing a great deal in equipment and manpower, and likely decreasing compliance. The fact that GALT's oral formulation is successful in combating NASH/NAFLD in a mouse model is very reassuring that eventually GR-MD-02 could be given as an oral treatment to patients. Also, it is technically much easier in the lab to demonstrate effects with an oral treatment rather than IV, as it's a much less stressful (and therefore less confounding) method of delivering a drug to a mouse; further preclinical trials with this oral method will be much cleaner due to the loss of stress-effects in the mice.
Overall, this isn't news to be over-the-moon about; GALT is already in clinical trials with IV dosage of GR-MD-02, and any potential failure in that study will set GR-MD-02 back severely, unless GALT can demonstrate that the oral route is far superior. This is certainly possible, but it would be painful for the company to have the clinical trial fizzle due to the dosage route, and have to go through the cost of reevaluating the safety and dosage of oral GR-MD-02 before finally being able to assay its efficacy. But (and this is a big but), it certainly allows a fall-back option that may give GALT new life in the case of Phase I/II failure.
GR-MD-02 again shows efficacy
It's always nice to see companies "repeat a positive"; another piece of evidence (in a preclinical trial) demonstrating the efficacy of GR-MD-02 in reducing liver damage and weight in diabetic/obese mice is always welcome. I am somewhat irritated, however, that no description of the type of "diabetic mice" that were used in the study is given, outside of the fact they were induced to become obese with high fat diet. It would have been nice to have some idea of how large these mice were exactly. Additionally, it is always interesting to see these treatments carried out in genetically obese mouse models, as it's easier to see a dramatic, robust change. There is a HUMONGOUS difference between a mouse fed high-fat diet (one standard method of creating a "diabetic" mouse) vs. a genetically obese, diabetic mouse (for instance, animals lacking either leptin (ob/ob) or leptin receptor (db/db) mice). See the pictures for a visual comparison. It's easier to show a significant improvement in the genetic models of obesity, simply because of how massive those animals are compared to their 'normal' sisters and brothers. Regardless, the actual data that were presented looked quite good, considering the changes in markers of liver damage.
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| Left: Normal mouse Right: High-fat fed mouse Source: University of Washington |
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| An ob/ob (leptin deficient) mouse Source |
Changes in liver size are confounding
It is questionable to me that there were significant differences in liver weight between the two groups (with the GR-MD-02-treated group having smaller livers). The data would have been much more provocative without these changes, as it is possible (if not very likely) that the reduction in liver size or triglyceride content (which was not reported alongside plasma triglyceride content) could be the driver of the actual effects of the drug. Although these animals were induced to become obese by a high fat diet, it is likely (in my experience with these models) that during the course of treatment with GR-MD-02, the high fat diet was continued to be fed (this is not specified in the release). It is therefor possible that GR-MD-02 was simply reducing the expansion liver. I'm really not sure, as it's not clear from the press release, but some more details would have been welcome in order to make an informed analysis. It would be beneficial, of course, if GR-MD-02 was also reducing the size of livers in patients, but in these preclinical studies I always prefer to see "cleanliness" rather than broad-stroke effects. Regardless, these aren't big confounding factors, and I still find the data compelling enough to reinforce my belief in the ultimate success of GR-MD-02.
GR-MD-02 is efficacious, orally
To me, this is the biggest revelation of this study. The current treatment regimen in GALT's phase I trial includes IV dosing of GR-MD-02, which is not ideal; it is harder to get a sustained effect of the drug, and requires frequent visits to a physician to receive the injections, costing a great deal in equipment and manpower, and likely decreasing compliance. The fact that GALT's oral formulation is successful in combating NASH/NAFLD in a mouse model is very reassuring that eventually GR-MD-02 could be given as an oral treatment to patients. Also, it is technically much easier in the lab to demonstrate effects with an oral treatment rather than IV, as it's a much less stressful (and therefore less confounding) method of delivering a drug to a mouse; further preclinical trials with this oral method will be much cleaner due to the loss of stress-effects in the mice.
Overall, this isn't news to be over-the-moon about; GALT is already in clinical trials with IV dosage of GR-MD-02, and any potential failure in that study will set GR-MD-02 back severely, unless GALT can demonstrate that the oral route is far superior. This is certainly possible, but it would be painful for the company to have the clinical trial fizzle due to the dosage route, and have to go through the cost of reevaluating the safety and dosage of oral GR-MD-02 before finally being able to assay its efficacy. But (and this is a big but), it certainly allows a fall-back option that may give GALT new life in the case of Phase I/II failure.
This is not a recommendation to engage in a trade or any financial decision.
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