A Trial of TTI-621 for Patients With Hematologic Malignancies and Selected Solid Tumors

This is a trial of TTI-621 in subjects with relapsed or refractory hematologic malignancies
and selected solid tumors.

TTI-621 (SIRPαFc) is a soluble recombinant fusion protein created by directly linking the
sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of
human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from
delivering an inhibitory "do not eat" (anti phagocytic) signal to macrophages.

This trial will be conducted in 2 phases: Phase 1a (escalation phase) and Phase 1b (expansion
phase).

In the dose Escalation Phase (phase 1a), subjects with lymphoma will be enrolled in
sequential dose cohorts to receive TTI-621 to characterize safety, tolerability,
pharmacokinetics, and the maximum-tolerated dose (MTD).

In the Expansion Phase (phase 1b), TTI-621 will be given to subjects with a variety of
hematologic malignancies and selected solid tumors to further define safety and to
characterize efficacy. In the Expansion Phase, the safety and efficacy of TTI-621 will also
be assessed when it is given in combination with other anti-cancer drugs. The dose of TTI-621
to be delivered in the Expansion Phase of the study may be increased or decreased based on
the subject's tolerability and on the subject's response to treatment.

Secondary objectives include further characterization of the pharmacokinetics,
pharmacodynamics, and development of ADA; and to gain preliminary evidence of the anti-tumor
activity of TTI-621 in subjects with a variety of hematologic malignancies and selected solid
tumors.

Inclusion Criteria:

1. Advanced measurable malignancy

2. Adequate hematologic status

3. Relapsed or are refractory following at least 2 prior systemic therapeutic attempts (1
prior systemic attempt for PTCL). For CTCL, extracorporal photochemotherapy (ECP) will
be considered a systemic therapy. Local radiation and topical agents are not systemic
therapies.

4. Adequate coagulation function

5. Adequate hepatic function

6. Adequate renal function

Exclusion Criteria:

1. Known, current central nervous system disease involvement or untreated brain
metastases

2. Allogeneic transplant within 30 days prior to the planned start of treatment or
subjects with active graft-vs-host disease with the exception of Grade 1 skin
involvement

3. History of hemolytic anemia or bleeding diathesis