Comments on: Micromet– More Reasons For Optimism http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/ Biotech stock reviews Sat, 13 Mar 2010 17:42:40 +0000 http://wordpress.org/?v=2.3.1 By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-787 Ohad Hammer Tue, 09 Jun 2009 13:46:47 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-787 Hi beo, MRD is the presence of tumor cells in the bone marrow, it is measured by looking at specific mutations the patients harbor. MT103 binds CD19, which is present on tumor cells. It has nothing to do with the identification of MRD. I am not aware of cases of retreatment following relapse. It's impossible to tell for sure whether patients will still respond to MT103. I can't explain the stock's behavior, but the data was very positive. ohad Hi beo,

MRD is the presence of tumor cells in the bone marrow, it is measured by looking at specific mutations the patients harbor.
MT103 binds CD19, which is present on tumor cells. It has nothing to do with the identification of MRD.

I am not aware of cases of retreatment following relapse. It’s impossible to tell for sure whether patients will still respond to MT103.

I can’t explain the stock’s behavior, but the data was very positive.

ohad

]]> By: beoX http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-785 beoX Mon, 08 Jun 2009 20:53:47 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-785 Ohad, a few questions. What molecular characteristic is used for monitoring of MRD? Is it the protein MT103 binds to? Is there any plan for situation that some of the pacients successfully trated with MT103 gets molecular relapse? Will MT103 tried again to keep the clone at bay? Would the cells still react? What is your opinion on todays rise +40% and following sell off? Was it because the investors dont understand MRD concept? Or they see target group as a very small? Thank you for answers. Ohad,
a few questions.
What molecular characteristic is used for monitoring of MRD? Is it the protein MT103 binds to?
Is there any plan for situation that some of the pacients successfully trated with MT103 gets molecular relapse? Will MT103 tried again to keep the clone at bay? Would the cells still react?

What is your opinion on todays rise +40% and following sell off? Was it because the investors dont understand MRD concept? Or they see target group as a very small?

Thank you for answers.

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-765 Ohad Hammer Tue, 02 Jun 2009 09:08:58 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-765 MITI said the issue of CNS events and identifying patients who are likely to develop them will be discussed in full detail at ASH, so everything is still pretty vague. Most CNS events are from the NHL study, which involves higher doses. I don't know whether there are other reasons besides the dose that could explain the difference. ohad MITI said the issue of CNS events and identifying patients who are likely to develop them will be discussed in full detail at ASH, so everything is still pretty vague.
Most CNS events are from the NHL study, which involves
higher doses. I don’t know whether there are other reasons besides the dose that could explain the difference.

ohad

]]> By: rick zhu http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-760 rick zhu Sat, 30 May 2009 20:46:41 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-760 Hi. Ohad I always appreciate your insight and analysis on biotech. Assuming CNS events are due to lymphoma cells, then CNS events will only happen in lymphoma patients who may have lymphoma cells in their brains. Hence CNS events will not happen in ALL(Acute Limphocytic Leukemia) patients who do not have lymphoma cells in their brains. May I know MT103 CNS events only occur in lymphoma patients and never occur in ALL patients at all? Thanks Hi. Ohad

I always appreciate your insight and analysis on biotech.

Assuming CNS events are due to lymphoma cells, then CNS events will only happen in lymphoma patients who may have lymphoma cells in their brains. Hence CNS events will not happen in ALL(Acute Limphocytic Leukemia) patients who do not have lymphoma cells in their brains.

May I know MT103 CNS events only occur in lymphoma patients and never occur in ALL patients at all?

Thanks

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-743 Ohad Hammer Wed, 27 May 2009 14:48:37 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-743 From what I recall, the company believes that the CNS events are caused by lymphoma cells in the CNS. My impression is that investigators can now identify these patients in advance and use low sneak-in dose as mitigation measure. I didn't hear anything about immunogenicity in that context. ohad From what I recall, the company believes that the CNS events are caused by lymphoma cells in the CNS. My impression is that investigators can now identify these patients in advance and use low sneak-in dose as mitigation measure. I didn’t hear anything about immunogenicity in that context.

ohad

]]> By: rick zhu http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-741 rick zhu Wed, 27 May 2009 14:06:23 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-741 Hi. Ohad: http://messages.finance.yahoo.com/Stocks_(A_to_Z)/Stocks_M/threadview?m=tm&bn=27685&tid=5273&mid=5273&tof=4&frt=2 Regarding CNS adverse events: "Predominantly during the first days of treatment, symptoms of the CNS, such as disorientation, confusion, speech disorders, tremor and convulsions, have been observed in some patients (7 out of 39 lymphoma patients, Grades 2 and 3). The nature of CNS events is not yet fully understood. So far, all CNS-related events were fully reversible during or shortly after discontinuation of treatment. Most adverse events, including CNS-related events, occurred during the first 3 days of treatment. In contrast, during several weeks of maintenance treatment, a much reduced incidence and intensity of adverse events have been observed. Most AEs (>95%) returned to grade ≤1 during ongoing treatment." Would you please give a guess here about that MT103 CNS adverse events are mostly related to T Cell cytokines' effect or something else, since immunogenecity would not be a big issue here? Thanks Hi. Ohad:
http://messages.finance.yahoo.com/Stocks_(A_to_Z)/Stocks_M/threadview?m=tm&bn=27685&tid=5273&mid=5273&tof=4&frt=2
Regarding CNS adverse events:
“Predominantly during the first days of treatment, symptoms of the CNS, such as disorientation, confusion, speech disorders, tremor and convulsions, have been observed in some patients (7 out of 39 lymphoma patients, Grades 2 and 3). The nature of CNS events is not yet fully understood. So far, all CNS-related events were fully reversible during or shortly after discontinuation of treatment. Most adverse events, including CNS-related events, occurred during the first 3 days of treatment. In contrast, during several weeks of maintenance treatment, a much reduced incidence and intensity of adverse events have been observed. Most AEs (>95%) returned to grade ≤1 during ongoing treatment.”

Would you please give a guess here about that MT103 CNS adverse events are mostly related to T Cell cytokines’ effect or something else, since immunogenecity would not be a big issue here?

Thanks

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-740 Ohad Hammer Wed, 27 May 2009 13:44:24 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-740 Off label use happens in oncology, but only if physicians have a very good reason and providing the drug is safe. TRION's drug is not approved for systemic therapy (intravenously)due to its prolbematic safety profile. This could change, but at the moment, I doubt that anyone would use it outside of the approved indication. If by MRD, you meant ALL, don't forget that TRION's antibody is not relevant for ALL. It may compete with MT110 in the future for solid tumors, if both agents get approved, but that's a big "if". To sum it all up, MITI is facing a lot of challenges, but TRION's Removab is not one of them, at the moment. ohad Off label use happens in oncology, but only if physicians have a very good reason and providing the drug is safe. TRION’s drug is not approved for systemic therapy (intravenously)due to its prolbematic safety profile. This could change, but at the moment, I doubt that anyone would use it outside of the approved indication.
If by MRD, you meant ALL, don’t forget that TRION’s antibody is not relevant for ALL. It may compete with MT110 in the future for solid tumors, if both agents get approved, but that’s a big “if”.

To sum it all up, MITI is facing a lot of challenges, but TRION’s Removab is not one of them, at the moment.

ohad

]]> By: beoX http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-739 beoX Wed, 27 May 2009 13:32:49 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-739 Thanks for your answer. One more thing came to my mind. How is it with offlabel use of anticancer drugs? TRION was approved for ovarian cancer but doctors might start using it for other malignacies including MRD. Selection of the diseases might be based on the results of ongoing MITIs clinical trials. Does this block MITIs future drug penetration? I mean wouldnt doctors stick to product they already have possitive experience even if they use it offlabel? This might be a naive question, I simply dont know how difficult it is (from the point of law and usual praxis) to use something offlabel in situation when there is or is not an alternative. I am looking forward to your opinion. Thanks for your answer.
One more thing came to my mind. How is it with offlabel use of anticancer drugs? TRION was approved for ovarian cancer but doctors might start using it for other malignacies including MRD. Selection of the diseases might be based on the results of ongoing MITIs clinical trials. Does this block MITIs future drug penetration? I mean wouldnt doctors stick to product they already have possitive experience even if they use it offlabel? This might be a naive question, I simply dont know how difficult it is (from the point of law and usual praxis) to use something offlabel in situation when there is or is not an alternative. I am looking forward to your opinion.

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-735 Ohad Hammer Wed, 27 May 2009 12:19:21 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-735 MITI still has an edge because its antibodies consist of the variable regions only, as opposed to TRION whose abs are whole antibodies (variable+ constant regions). Most of the immunogenicity is caused by the constant regions so it that sense, MT103 is as immunogenic as Rituxan or Erbitux, which are chimeric antibodies. Theoretically, even a slight difference in the amino acid sequence of a protein can lead to different/better/worse function so this could be regarded as a different drug. However, the issue is very complicated because there are a lot of factors, especially intellectual property issues that may prevent the generation of similar proteins. With respect to MITI's MT110 vs. TRION's Removab, there is no such problem, as the two abs are totally unrelated. The only challenge MT110 will face is succeeding in a registration trial. ohad MITI still has an edge because its antibodies consist of the variable regions only, as opposed to TRION whose abs are whole antibodies (variable+ constant regions). Most of the immunogenicity is caused by the constant regions so it that sense, MT103 is as immunogenic as Rituxan or Erbitux, which are chimeric antibodies.

Theoretically, even a slight difference in the amino acid sequence of a protein can lead to different/better/worse function so this could be regarded as a different drug.
However, the issue is very complicated because there are a lot of factors, especially intellectual property issues that may prevent the generation of similar proteins.

With respect to MITI’s MT110 vs. TRION’s Removab, there is no such problem, as the two abs are totally unrelated. The only challenge MT110 will face is succeeding in a registration trial.

ohad

]]> By: beoX http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-734 beoX Wed, 27 May 2009 10:45:13 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-734 So when both TRIOMABs and MITIs Abs are nonhumanized does MITI still have an edge? In fact I intended to buy MITI but now I am not that sure. TRIomas Ab is immonogenic (probably published) and MITIs not or this information is not avialable? More general question - how different two antibodies (or biologics in general} have to be in order to be approved as two different therapeutical entities? And back to MITI is there a chance that it will be approved in Europe with TRIOMAB already approved? Thanks for your answer. So when both TRIOMABs and MITIs Abs are nonhumanized does MITI still have an edge? In fact I intended to buy MITI but now I am not that sure. TRIomas Ab is immonogenic (probably published) and MITIs not or this information is not avialable?

More general question - how different two antibodies (or biologics in general} have to be in order to be approved as two different therapeutical entities? And back to MITI is there a chance that it will be approved in Europe with TRIOMAB already approved?

Thanks for your answer.

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-730 Ohad Hammer Tue, 26 May 2009 17:22:47 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-730 It appears you are right, MT103 is murine. my mistake. http://www.micromet.de/fileadmin/template/main/pdf/publications_2f24e6564059fd41eb13f1847c4f7d8d.pdf I am not sure about other BiTE antibodies. ohad It appears you are right, MT103 is murine. my mistake.

http://www.micromet.de/fileadmin/template/main/pdf/publications_2f24e6564059fd41eb13f1847c4f7d8d.pdf

I am not sure about other BiTE antibodies.

ohad

]]> By: Rick http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-728 Rick Tue, 26 May 2009 16:28:05 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-728 Ohad: Hi. Are you very sure that MITI BiTE are humanized MAb? I saw you said in your blog that MITI BiTE is humanized or chimeric MAb. Did you get that info from any professional journal article? From what I read on many professional journal articles about MITI's BiTE so far in which they all stated that MITI BiTE are made from mouse MAb. I would like to confirm this whichever way it may be. Thanks very much in advance. Ohad: Hi.

Are you very sure that MITI BiTE are humanized MAb?

I saw you said in your blog that MITI BiTE is humanized or chimeric MAb.

Did you get that info from any professional journal article?

From what I read on many professional journal articles about MITI’s BiTE so far in which they all stated that MITI BiTE are made from mouse MAb.

I would like to confirm this whichever way it may be.

Thanks very much in advance.

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-698 Ohad Hammer Wed, 13 May 2009 07:56:06 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-698 There is no concern with regards to MITI's antibody source, as they use humanized antibodies as far as I know. TRION do not use chimeric or humanized antibodies but entirely non-human sequences, which is why patients develop an immune response against the drug. What I meant to say is that both TRION and MITI use similar mechanisms of action which could lead to production of cytokines. So far, MITI's safety profile is clean as opposed to TRION's safety profile which is problematic. It has nothing to do with immunogenicity. Besides ABGX and MEDX, there are also CAT (now part of Medimmune) and Morphosys, which I previously wrote about. MITI could license the technology but based on the evidence thus far, there is not much of an advantage for fully human antibodies in terms of immune response. Best, ohad There is no concern with regards to MITI’s antibody source, as they use humanized antibodies as far as I know. TRION do not use chimeric or humanized antibodies but entirely non-human sequences, which is why patients develop an immune response against the drug.

What I meant to say is that both TRION and MITI use similar mechanisms of action which could lead to production of cytokines. So far, MITI’s safety profile is clean as opposed to TRION’s safety profile which is problematic. It has nothing to do with immunogenicity.

Besides ABGX and MEDX, there are also CAT (now part of Medimmune) and Morphosys, which I previously wrote about. MITI could license the technology but based on the evidence thus far, there is not much of an advantage for fully human antibodies in terms of immune response.

Best,
ohad

]]> By: Bill http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-697 Bill Wed, 13 May 2009 07:40:17 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-697 Ohad: Thanks very much for your reply. I appreciate your analysis and insight. I share with your concern on MITI's antibody source. I read some articles on MITI's MAb which are from mouses. Hence it may induce immune rejection in humans. As you described that Removab MAb souce is half from mouse and half from rat. This is even worse, being more likely to induce immune rejection. However, sgen and imgn do not use pure human antibody either from what I read a few years ago. They are using "humanized" antibodies. It changed some chemical structure to make it look like human and not 100% pure human. Hence I guess it may be still possible to induce immune rejection to some minor degree. There has been two companies abgx (acquired a few years ago) and medx, which can produce full human antibody. I guess if MITI can use Mederax pure human antibody, that will be an ideal match. Ohad:

Thanks very much for your reply.
I appreciate your analysis and insight.

I share with your concern on MITI’s antibody source. I read some articles on MITI’s MAb which are from mouses. Hence it may induce immune rejection in humans. As you described that Removab MAb souce is half from mouse and half from rat. This is even worse, being more likely to induce immune rejection.

However, sgen and imgn do not use pure human antibody either from what I read a few years ago. They are using “humanized” antibodies. It changed some chemical structure to make it look like human and not 100% pure human. Hence I guess it may be still possible to induce immune rejection to some minor degree.

There has been two companies abgx (acquired a few years ago) and medx, which can produce full human antibody.

I guess if MITI can use Mederax pure human antibody, that will be an ideal match.

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-696 Ohad Hammer Wed, 13 May 2009 04:37:09 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-696 Hi Bill From I understand, in order to overcome stability and production issues, TRIOMABs are half mouse half rat. This is in contrast to most commercial antibodies, which are mainly made of human sequences. As a result, the immune system identifies TRIOMABs as foreign objects and neutralizes them, so they cannot be given for a large number of cycles. Regardless, TRIOMABs also lead to increased cytokine release that leads to adverse events. Actually, this is exactly what I was afraid of in MITI's case but so far so good... This is why Removab was not developed as a systemic treatment (IV) but was injected into the peritoneal cavity. There might be something I am missing, but as far as I can tell, MITI's platform is far superior. I assume you are referring to MT201 (MT203 is the anti- GMCSF antibody), which is a conventional antibody whereas MT110 is BiTE antibody. MT110 is a wild card because it has no clinical data but if it works, it’s going to be huge. MT202 on the other hand, has plenty of data and so far results are not exciting. Ohad Hi Bill

From I understand, in order to overcome stability and production issues, TRIOMABs are half mouse half rat. This is in contrast to most commercial antibodies, which are mainly made of human sequences. As a result, the immune system identifies TRIOMABs as foreign objects and neutralizes them, so they cannot be given for a large number of cycles.
Regardless, TRIOMABs also lead to increased cytokine release that leads to adverse events. Actually, this is exactly what I was afraid of in MITI’s case but so far so good…

This is why Removab was not developed as a systemic treatment (IV) but was injected into the peritoneal cavity.

There might be something I am missing, but as far as I can tell, MITI’s platform is far superior.

I assume you are referring to MT201 (MT203 is the anti- GMCSF antibody), which is a conventional antibody whereas MT110 is BiTE antibody. MT110 is a wild card because it has no clinical data but if it works, it’s going to be huge. MT202 on the other hand, has plenty of data and so far results are not exciting.

Ohad

]]> By: Bill http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-695 Bill Tue, 12 May 2009 23:26:58 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-695 Hi. Ohad: You mentioned "TRION’s platform suffers from multiple drawbacks. These drawbacks, especially the drug’s safety profile and immunogenicity, substantially limit the potential use of TRION’s products." Could you please provide more detailed info on what are specific drawbacks of safety and immunogenicity of Trion's Removab? Another question is while MT203 is also targeted EpCAM as does MT110, MT203 is in phase 2 and MT110 is in phase 1, could you please compare those two and also explain why you would say MT110 is a wild card while MT203 is not? Thanks Hi. Ohad:
You mentioned “TRION’s platform suffers from multiple drawbacks. These drawbacks, especially the drug’s safety profile and immunogenicity, substantially limit the potential use of TRION’s products.”

Could you please provide more detailed info on what are specific drawbacks of safety and immunogenicity of Trion’s Removab?

Another question is while MT203 is also targeted EpCAM as does MT110, MT203 is in phase 2 and MT110 is in phase 1, could you please compare those two and also explain why you would say MT110 is a wild card while MT203 is not?

Thanks

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-694 Ohad Hammer Mon, 11 May 2009 23:11:19 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-694 INCY is looking really good recently. I hope it implies that the debt issue is going to be resolved soon. Unfortunately, I am limited in the amount of articles I can write, for every 3-4 pieces I want to publish I can do only one, so I can't promise anything, but INCY is definitely one of the stocks I follow closely and would love to do a write up on it. The following posts will probably be about ASCO related news. ohad INCY is looking really good recently.
I hope it implies that the debt issue is going to be resolved soon. Unfortunately, I am limited in the amount of articles I can write, for every 3-4 pieces I want to publish I can do only one, so I can’t promise anything, but INCY is definitely one of the stocks I follow closely and would love to do a write up on it.
The following posts will probably be about ASCO related news.

ohad

]]> By: denny http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-691 denny Mon, 11 May 2009 18:16:26 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-691 Ohad, INCY was mentioned by Dr. Hans Black of Interinvest as number one choice. What do you think about this: http://www.pbs.org/nbr/site/onair/transcripts/market_monitor_dr_hans_black_says_rally_is_real_090508/ Are you going to write up anything on INCY soon. Thanks Ohad,

INCY was mentioned by Dr. Hans Black of Interinvest as number one choice. What do you think about this:

http://www.pbs.org/nbr/site/onair/transcripts/market_monitor_dr_hans_black_says_rally_is_real_090508/

Are you going to write up anything on INCY soon.

Thanks

]]> By: Insight http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-690 Insight Mon, 11 May 2009 16:44:10 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-690 Hi Ohad, Incyte is finally taking off today...it was mentioned on some news on Friday. Were you going to do a write up on them soon? TIA. Hi Ohad, Incyte is finally taking off today…it was mentioned on some news on Friday. Were you going to do a write up on them soon? TIA.

]]> By: Ohad Hammer http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-689 Ohad Hammer Mon, 11 May 2009 16:09:26 +0000 http://www.hammerstockblog.com/micromet%e2%80%93-more-reasons-for-optimism/#comment-689 Hi Alex The deal is positive and could be leveraged to get some highly needed $$$. I have to say I was somewhat disappointed by the deal terms which were probably a result of the company's weak balance sheet. ROSG decided not to dilute its shareholders for the time being, but it seems it will have to, sooner or later. The company's technology is still one of the most exciting stuff in biotech imo. ohad Hi Alex

The deal is positive and could be leveraged to get some highly needed $$$. I have to say I was somewhat disappointed by the deal terms which were probably a result of the company’s weak balance sheet. ROSG decided not to dilute its shareholders for the time being, but it seems it will have to, sooner or later.
The company’s technology is still one of the most exciting stuff in biotech imo.

ohad

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