Key Features:

      - This is a Phase 1/2 clinical study conducted in patients with newly diagnosed high-risk
      multiple myeloma to examine the effects of GPS immunotherapy on clinical and immunobiological
      indices. The study is titled "A Pilot Trial of a WT1 Analog Peptide Vaccine (Galinpepimut-S)
      in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation" and is
      designed as a single-arm, single-institution, open-label study.

      Rationale:

      - Overexpression of WT1 in multiple myeloma (MM) cells has been demonstrated by
      immunocytochemistry (IHC) and in HLA-A*0201 patients by staining with a high-affinity fully
      human IgG1 mAb (ESK1) specific to the RMFPNAPYL/HLA-A*0201 complex on malignant plasma cells.
      WT1 also serves as a target for antigen-specific directly immunizing immunotherapeutic
      approaches, such as peptide vaccines (in this case, galinpepimut-S), in patients with
      multiple myeloma. Patients with persistent plasma cell leukemia following CD34+-selected
      allografts treated with adoptive transfer of donor-derived WT1-specific cytotoxic T cells are
      capable of achieving long-lasting complete remission (CR) status, thus underscoring the
      therapeutic potential of activated T-cells specifically immunized against WT1 peptides. The
      above provide the theoretical basis for the possibility of successful immunization after
      exposure to a WT1-specific vaccine (such as galinpepimut-S), whereby WT1-sensitized
      T-lymphocytes (both CD8+ and CD4+) from vaccinated MM could be directed to antigen (WT1)
      expressed on malignant plasma cells.

      Galinpepimut-S (GPS) - Key features:

      - GPS is a tetravalent peptide vaccine, consisting of an equiweight mixture of 4 WT1-derived
      peptides which have been chosen to strengthen antigenicity, but also broaden immunogenicity
      over a wide range of HLA subtypes, being able to stimulate both CD8+ (MHC Class I)- and CD4+
      (MHC Class II)-dependent responses. Of note, 2 of the 4 peptides are heteroclitic, i.e.,
      carry by-design introduced missense mutations, in order to decrease tolerogenicity (as these
      modified peptides are no longer identified as "self" moieties by the vaccinated host's immune
      system. GPS contains one heteroclitic peptide (WT1-A1) to stimulate CD8+ responses, two
      longer native peptides (427 long and 331 long) to stimulate CD4+ responses and one longer
      heteroclitic peptide (122A1 long) that is capable of stimulating both CD8+ and CD4+ cells
      (with the CD8-activating shorter sequence/locus 'buried' with the lengthier CD4-activating
      one). Galinpepimut-S is always mixed in emulsion with the immunological adjuvant Montanide™
      and is administered after granulocyte-macrophage colony-stimulating factor (GM-CSF;
      sargramostine; Leukine®) pre-stimulation.

      Putative Mechanism of action (MOA) of galinpepimut-S in MM:

      - Galinpepimut-S (GPS) is a peptide immunogen of the vaccine type, capable of inducing in the
      treated host WT1-specific antigenicity and eventual systemic immunogenicity against
      WT1-expressing deposits of cancerous cells. The above principles are applicable in MM
      patients treated with this immunotherapeutic. It is very likely that the antigen presenting
      cell (APC)-CD8-CD4 cross-activating circuits are markedly amplified in subjects receiving
      galinpepimut-S, leading to specific and direct immunization against WT1 and eventual killing
      of WT1-expressing malignant plasma cells via activated immunocytes (mainly lymphocytes and
      natural killer [NK] cells). This MOA represents a plausible model for the immunobiological
      basis of the observed clinical activity of galinpepimut-S against various tumor types (other
      than MM) tested to-date, and is poised to be applicable in MM as well.