Therapeutic Product Immunogenicity Community

Dear TPI community,

An interesting question was raised by Sophie Tourdot and we wanted to bring it to the community for feedback. Its acknowledged that information surrounding clinical failures due to immunogenicity would be hugely valuable to the community at large, however program failures often do not get published or publicly disclosed. We would like your opinions on whether you think it would be feasible and if you would be interested in sourcing the following from your organization:
  
(1) General stats on the number of clinical failures from your organization that can be attributed to immunogenicity liabilities (total number of failures, time period in which these numbers are being reported (e.g. 2000-2024), furthest clinical phase reached, modality, etc.). We could make these as anonymized as necessary, submitting anonymously and lacking any connection to the organization, target, etc..

(2) Detailed information on failed molecules (modality, sequence, target, clinical immunogenicity measures, preclinical measures, etc.).   

If either of these seem feasible, we could consider conducting a survey or creating a working group to gather and publish on these data to be utilized by the field at large.

Thanks,
Dan

Dear TPI community,

An interesting question was raised by Sophie Tourdot and we wanted to bring it to the community for feedback. Its acknowledged that information surrounding clinical failures due to immunogenicity would be hugely valuable to the community at large, however program failures often do not get published or publicly disclosed. We would like your opinions on whether you think it would be feasible and if you would be interested in sourcing the following from your organization:
  
(1) General stats on the number of clinical failures from your organization that can be attributed to immunogenicity liabilities (total number of failures, time period in which these numbers are being reported (e.g. 2000-2024), furthest clinical phase reached, modality, etc.). We could make these as anonymized as necessary, submitting anonymously and lacking any connection to the organization, target, etc..

(2) Detailed information on failed molecules (modality, sequence, target, clinical immunogenicity measures, preclinical measures, etc.).   

If either of these seem feasible, we could consider conducting a survey or creating a working group to gather and publish on these data to be utilized by the field at large.

Thanks,
Dan

Hi Dan,

I think this will be an interesting undertaking.  I suspect examples of true clinical failure will be relatively rare compared to the many programs that will have been cancelled due to perceived immunogenicity liability that was not true clinical failure - a portfolio decision to cancel a program due to 'high immunogenicity incidence' that is attributable to overly sensitive assays that capture irrelevant signals is not a clinical failure.  It might be challenging to untangle these cases - but a very worthwhile undertaking if it can recalibrate people's mindsets as to what constitutes clinically relevant immunogenicity and liability.

Thanks

Lauren

Dear TPI community,

An interesting question was raised by Sophie Tourdot and we wanted to bring it to the community for feedback. Its acknowledged that information surrounding clinical failures due to immunogenicity would be hugely valuable to the community at large, however program failures often do not get published or publicly disclosed. We would like your opinions on whether you think it would be feasible and if you would be interested in sourcing the following from your organization:
  
(1) General stats on the number of clinical failures from your organization that can be attributed to immunogenicity liabilities (total number of failures, time period in which these numbers are being reported (e.g. 2000-2024), furthest clinical phase reached, modality, etc.). We could make these as anonymized as necessary, submitting anonymously and lacking any connection to the organization, target, etc..

(2) Detailed information on failed molecules (modality, sequence, target, clinical immunogenicity measures, preclinical measures, etc.).   

If either of these seem feasible, we could consider conducting a survey or creating a working group to gather and publish on these data to be utilized by the field at large.

Thanks,
Dan

Eric and Lauren,

Yes, the intention would be to identify molecules/programs where immunogenicity liabilities were a primary factor in them not proceeding further in development. This could be due to perceived risk from unacceptable rates of ADA or actual clinical impact (ADA rates/titers linked to impacts on PK, efficacy or safety). Either way, the molecule didn't proceed because of immunogenicity liabilities.

Even if companies were willing to share this information, it may not exists in an aggregated, readily accessible format. That aspect is definitely one major part of the feasibility question. 

Hi Dan,

I think this will be an interesting undertaking.  I suspect examples of true clinical failure will be relatively rare compared to the many programs that will have been cancelled due to perceived immunogenicity liability that was not true clinical failure - a portfolio decision to cancel a program due to 'high immunogenicity incidence' that is attributable to overly sensitive assays that capture irrelevant signals is not a clinical failure.  It might be challenging to untangle these cases - but a very worthwhile undertaking if it can recalibrate people's mindsets as to what constitutes clinically relevant immunogenicity and liability.

Thanks

Lauren

Dear TPI community,

An interesting question was raised by Sophie Tourdot and we wanted to bring it to the community for feedback. Its acknowledged that information surrounding clinical failures due to immunogenicity would be hugely valuable to the community at large, however program failures often do not get published or publicly disclosed. We would like your opinions on whether you think it would be feasible and if you would be interested in sourcing the following from your organization:
  
(1) General stats on the number of clinical failures from your organization that can be attributed to immunogenicity liabilities (total number of failures, time period in which these numbers are being reported (e.g. 2000-2024), furthest clinical phase reached, modality, etc.). We could make these as anonymized as necessary, submitting anonymously and lacking any connection to the organization, target, etc..

(2) Detailed information on failed molecules (modality, sequence, target, clinical immunogenicity measures, preclinical measures, etc.).   

If either of these seem feasible, we could consider conducting a survey or creating a working group to gather and publish on these data to be utilized by the field at large.

Thanks,
Dan

Eric and Lauren,

Yes, the intention would be to identify molecules/programs where immunogenicity liabilities were a primary factor in them not proceeding further in development. This could be due to perceived risk from unacceptable rates of ADA or actual clinical impact (ADA rates/titers linked to impacts on PK, efficacy or safety). Either way, the molecule didn't proceed because of immunogenicity liabilities.

Even if companies were willing to share this information, it may not exists in an aggregated, readily accessible format. That aspect is definitely one major part of the feasibility question. 

Hi Dan,

I think this will be an interesting undertaking.  I suspect examples of true clinical failure will be relatively rare compared to the many programs that will have been cancelled due to perceived immunogenicity liability that was not true clinical failure - a portfolio decision to cancel a program due to 'high immunogenicity incidence' that is attributable to overly sensitive assays that capture irrelevant signals is not a clinical failure.  It might be challenging to untangle these cases - but a very worthwhile undertaking if it can recalibrate people's mindsets as to what constitutes clinically relevant immunogenicity and liability.

Thanks

Lauren

Dear TPI community,

An interesting question was raised by Sophie Tourdot and we wanted to bring it to the community for feedback. Its acknowledged that information surrounding clinical failures due to immunogenicity would be hugely valuable to the community at large, however program failures often do not get published or publicly disclosed. We would like your opinions on whether you think it would be feasible and if you would be interested in sourcing the following from your organization:
  
(1) General stats on the number of clinical failures from your organization that can be attributed to immunogenicity liabilities (total number of failures, time period in which these numbers are being reported (e.g. 2000-2024), furthest clinical phase reached, modality, etc.). We could make these as anonymized as necessary, submitting anonymously and lacking any connection to the organization, target, etc..

(2) Detailed information on failed molecules (modality, sequence, target, clinical immunogenicity measures, preclinical measures, etc.).   

If either of these seem feasible, we could consider conducting a survey or creating a working group to gather and publish on these data to be utilized by the field at large.

Thanks,
Dan