Hi Michael,

Lower dose of therapeutic mAb not must generate lower side effects. Key problem is "nonlinear" and sometimes not predictable responce from immune system.

Probably you can find some answer if you check number of specific ADR's for currently approved mAbs (http://www.adrreports.eu/en/search.html#)

Of course data for different doses are not currently available but if dose have really critical impact on number of ADR's then between few different IgG1 mAbs (for example) should be significant diferences in ADR's profiles. If you check few mAbs representing the same class of IgG you should get partial answer because all monoclonals have different doses ..... So if dose is most critical source of high or low ADRs then within different IgG1 mAb's you should find significant correlation. If not that mean dose level is not most critical factor influencing ADR's profile or number.

Another problem is linked to immunosupression in case of higher doses or repeated doses. For example in case of some therapeutic mAb's afer many doses ADA levels are lower than after first doses. Effect is significant because huge immunosupresion made by drug. So in case some mAb's higher doses or multiple doses prevent for ADA. Such process could have potential link with ADR's number too.

Personally I think that number of ADR's in case of lower dose the same mAb could be different (different profile) but more less the same number .... but question is of course open and very inspirative .....

Best regards,

Thank you very much for Tomasz. I think your answer makes a lot of sense. Thank you for taking the time to answer my question. All the Best Mike

Dear Michael

This is a very inspiring question for me., finally more important fields related to ADRs profile from my point of view are:

- immunosuppresion/immunetolerance potential

- mechanism of action

- mode of action

- dosing intervals and number

I think its more valuable "covariates" for future risk analysis (related to impact of dose on ADRs) than for example dose level. Generally Its really good idea for scientific paper :-)

Best regards

Tomasz

Dear Tomasz: You are absolutely correct. However, I will leave the paper writing to you :) I am more on the business side at this stage.

Thank you again

Best Mike

Dear Michael. I think it could be my goal for next year :)

Best regards.

Tomasz

That sounds great. Best of luck. I will definitely read it once the manuscript comes out. Best Mike

Thank you! Best regards.

Tomasz