Coherus BioSciences, Inc.: toripalimab-tpzi

Health Service Act for (toripalimab-tpzi) injection.

If you chose to resubmit the application, provide revised ADLB datasets conforming to data specifications found at https://www.fda.gov/media/133252/download, for the pooled safety sample of patients treated with toripalimab at 3 mg/kg every 2 weeks (N=851) and a separate dataset for the POLARIS-02/Cohort 3 trial (N=190).

4. For the post-platinum treatment as monotherapy indication, you proposed both a weight-based dose of 3 mg/kg every two weeks (Q2W) a]

You may respond to deficiencies in this Complete Response Letter while the travel restrictions remain in effect.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed with regard to your application.

1. In Amendment 41(received March 21, 2017), for treatment emergent persistent anti-drug antibodies (ADA) with a titer > 2, you report an ADA incidence of 9.8% in the CHS-1701 arm and an incidence of 5.0% in the US-licensed Neulasta arm.

Coherus conducted statistical analysis of ADA incidence yielding a 1-sided upper exact limit of 10%, while the FDA performed independent analysis of your data and obtained a 1-sided upper exact limit of 10.97%.

Your observed difference in ADA between groups may not be sufficient to support a demonstration that there are no clinically meaningful differences between CHS-1701 and US-licensed Neulasta.

US-licensed Neulasta because the actual baseline immunogenicity rate for pegylated G-CSF products is expected to be lower and the 10% difference was selected to support a feasible study design.

The first NAb assay was submitted with the original BLA on August 9, 2016, and the second NAb assay was submitted in an amendment on January 18, 2017. Both NAb assays, are inadequate for the reasons listed below and will not allow for meaningful evaluation of NAb in clinical samples.

'You can revise one of the two NAb assays submitted to the BLA or develop a new NAb assay.

Sor Immunogenicity Testing of Therapeutic Protein Product, April 2016" for recommendations on assay validation.

The condition of the M-NFS-60 cells, including passage number, cell density, and cell viability, may affect the cellular response to CHS-1701 and mIL-3. However, you have not provided developmental data to support these cell related parameters specified in the assay validation report.

Regarding the neutralizing antibody assay ("/) submitted on January 18, 2017:

Assay Development for Immunogenicity Testing of Therapeutic Proteins, April 2016 regarding recommendations for reporting intra- and inter-assay precision for NC.

However, you did not evaluate the potency of CHS-1701 and USlicensed Neulasta in the forced degradation study included in the analytical similarity assessment and you did not demonstrate that potency of both products is affected to similar extents when subjected to forced degradation conditions.

You stated that limited supply of this material has been returned from the clinical site and potency testing for this lot "can be submitted to the BLA upon Agency's request.

Additionally, there are many inconsistencies, missing information, and typographical errors throughout your BLA. We expect that you will address these, and other such issues in any resubmission.

FDA-2017-P-2803) regarding certain aspects of applications submitted under section 351(k) of the PHS Act referencing Neulasta (pegfilgrastim).

If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under 21 CFR 601.3(c).