Below is a description of the four most advanced clinical programs that we are developing, their stage in
the drug development process and our expected future development plans. Each of these programs is
wholly-owned by Array.
Current Development Status
Future Development Plan
Phase 2 single agent and Phase 1b
Complete and report data from the
combination trials in patients with
Phase 2 and 1b trials and, if positive
results, advance into registration
Phase 1 dose escalation trial with an
Meet with the FDA to discuss
optimized formulation in patients
development plan to support
with myelodysplastic syndromes.
registration. If continued positive
results with the optimized
formulation, advance into registration
Completed Phase 2 randomized,
Seek an appropriate partner to
double blind study in osteoarthritis
maximize value of ARRY-797, given
the scope of a development program
28-day Phase 2 trial in patients with
Report top-line results from
Phase 2a trial and seek to partner.
ARRY-520 -- KSP Program for Multiple Myeloma
ARRY-520 is a potent, selective KSP inhibitor; its mechanism of action is distinct from other drugs used to
treat MM. In preclinical studies, ARRY-520 treatment resulted in a rapid onset of apoptosis in tumor cells
that depend on the MCL-1 survival protein. MM and other hematologic cancers frequently depend on
MCL-1 as a key survival protein, which supports investigation of ARRY-520 in MM. In clinical studies,
ARRY-520 has demonstrated durable, single-agent activity in patients with MM that is refractory to both
(bortezomib) and Revlimid (lenalidomide), a population with significant unmet therapeutic
needs. ARRY-520 is highly active in animal models of MM and synergy was observed when combined
with Velcade or Revlimid. These data support the ongoing investigation of ARRY-520 in combination with
Velcade and KyprolisTM (carfilzomib), which may enable development opportunities in earlier lines of
Array presented Phase 1 and Phase 2 clinical data for ARRY-520 at the December 2011 Annual Meeting
of the American Society of Hematology (ASH). In these studies, ARRY-520 showed preliminary clinical
activity in heavily pre-treated patients with MM and was generally well-tolerated.
In the Phase 2 trial, ARRY-520 demonstrated promising activity in patients with relapsed or refractory MM
who had received both a proteasome inhibitor and an IMiD-based regimen. Objective responses ( MR)
were observed in six patients (19%), with four confirmed partial responses and two minor responses.
Importantly, ARRY-520 demonstrated an 18% response rate (minor response or better) in patients with
MM refractory to both Revlimid and Velcade.
Development Status: During fiscal 2012, we:
· continued a Phase 2 trial in combination with dexamethasone in patients with MM refractory to
Revlimid, Velcade and dexamethasone therapy;
· continued a Phase 1b trial of ARRY-520 in combination with Velcade plus dexamethasone in
patients with relapsed and refractory MM; and
· collaborated with M.D. Anderson and Onyx Therapeutics, Inc. on an investigator-sponsored
Phase 1b study of ARRY-520 in combination with Kyprolis
(carfilzomib) in patients with relapsed
or refractory MM who are refractory or intolerant to Velcade.
During fiscal 2013, we plan to:
· report results from the Phase 2 study of ARRY-520 in combination with dexamethasone, interim
results from the Phase 1b study of ARRY-520 in combination with Velcade and dexamethasone
and interim results from the Phase 1b study of ARRY-520 in combination with Kyprolis; and
· pending positive results in either of the above trials, define a path to late stage development for
ARRY-520 in MM.
ARRY 614 -- p38/Tie2 Program for Myelodysplastic Syndromes
ARRY-614's dual p38/Tie2 inhibitor offers a unique mechanism of action for the treatment of
myelodysplastic syndromes (MDS). p38 and Tie2 are dysregulated in the bone marrow of patients with
MDS. ARRY-614 enables the repopulation of red blood cells, platelets and neutrophils and is believed to
restore bone marrow function by blocking myelosuppression. ARRY-614 inhibits inflammation and
cytokine-dependent tumor growth in preclinical models.
MDS are diseases characterized by over-production of myelosuppressive cytokines leading to aberrant
apoptosis in hematologic progenitor cells and peripheral cytopenias. p38 MAP kinase (p38) is implicated
in dysregulation of apoptosis and myelosuppressive cytokine signaling and production. Tie2 may affect
this process by promoting cytokine production and altering stromal cell quiescence. It is hypothesized that
disrupting cytokine-driven apoptosis in the normal progenitors and stromal cells may improve
hematopoiesis in MDS patients.
Array presented positive clinical data for ARRY-614 at the December 2011 ASH and June
2012 European Hematology Association (EHA) meetings. ARRY-614 demonstrated activity as measured
by hematologic improvement (increased neutrophils, platelets and/or red blood cells) in patients with
MDS and was generally well-tolerated.