Replies to post #130446 on Biotech Values

[mcbio]

Here are the ARRY-520 abstracts I found

ARRY-520 Shows Durable Responses in Patients with Relapsed/Refractory Multiple Myeloma in a Phase 1 Dose-Escalation Study ?
ash.confex.com/ash/2011/webprogram/Paper41766.html

The Novel KSP Inhibitor ARRY-520 Demonstrates Single-Agent Activity in Refractory Myeloma: Results From a Phase 2 Trial in Patients with Relapsed/Refractory Multiple Myeloma (MM)
ash.confex.com/ash/2011/webprogram/Paper40171.html

Thanks ghmm. What are your thoughts on the abstracts? Regarding the Phase 1 dose escalation trial in 31 relapsed/refractory MM patients, I guess it's important to note that patients were relapsed/refractory to both Velcade and an IMID, including 4 that were apparently relapsed/refractory to carfilzomib. There were 3 confirmed PRs and 1 confirmed minimal response. Duration of the PRs was 3.4 months, 11.9 months, and 12 months so sounds like a pretty durable response in the relatively small sample of patients that do have a response. Looks like four patients also had SD lasting >10 months. So, it's a relatively small number of patients that experience a response, but these are highly relapsed/refractory patients, and the responses do seem to be fairly durable.

Sounds like a somewhat similar patient population in the Phase 2 single-agent abstract. Out of 32 highly relapsed/refractory MM patients, 3 PRs, 2 confirmed minimal responses. The abstract also notes that 5/15 patients refractory to both Velcade and Revlimid achieved clinical benefit (PR+MR+SD > 4 months).

All told, I can't say that I'm blown away by the results, but they do seem encouraging and it looks like 520 does have activity in what is a highly refractory/relapsed MM patient population. I do think carfilzomib has clearly shown better results than 520, but presumably there is still a role for an agent that could work in patients relapsed/refractory to carfilzomib (not clear that the 4 patients in the Phase 1 who were relapsed/refractory to carfilzomib did have a response but 520 is a different MoA so presumably the potential is there) and there are also studies that will test 520 in combo with carfilzomib.

[mcbio]

ARRY - 520 ASH PR

http://finance.yahoo.com/news/ARRY-520-Demonstrates-Durable-bw-3061218676.html?x=0

ARRY-520 Demonstrates Durable Single-Agent Activity in Patients with Advanced Multiple Myeloma

BOULDER, Colo.--(BUSINESS WIRE)-- Array BioPharma Inc. (NASDAQ: ARRY - News) today announced Phase 1 and Phase 2 clinical data for its novel kinesin spindle protein (KSP) inhibitor, ARRY-520, at the 2011 Annual Meeting of the American Society of Hematology (ASH) in San Diego, California. These data indicate that ARRY-520 has shown preliminary clinical activity in heavily pre-treated patients with multiple myeloma (MM) and was generally well tolerated. The posters are summarized below and PDF versions are available for download on Array's website at www.arraybiopharma.com.

“ARRY-520 has a distinct mechanism of action compared with current and experimental drugs in myeloma and has shown promising single-agent activity,” said Sagar Lonial, M.D., Professor and Vice Chair of Clinical Affairs in the Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, Ga. “Particularly notable is the activity in patients with disease refractory to IMiD and proteasome inhibitor therapy, a patient population with significant unmet need. I am enthusiastic about its potential both as a single agent and in combination therapy.”

The Novel KSP Inhibitor ARRY-520 Demonstrates Single-Agent Activity in Refractory Myeloma:
Results From a Phase 2 Trial in Patients with Relapsed/Refractory Multiple Myeloma (MM)
(Abstract # 2935)
Presenter: Sagar Lonial, M.D., Professor and Vice Chair of Clinical Affairs in the Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine

This Phase 2, Simon 2-stage, open-label, multicenter trial evaluated single-agent ARRY-520 administered IV at 1.50 mg/m2/day on day 1 and day 2 repeated every 14 days with prophylactic granulocyte-colony stimulating factor (G-CSF) support. This study enrolled 32 patients with relapsed or refractory MM who had received both a proteasome inhibitor and an IMiD-based regimen. ARRY-520 demonstrated promising activity in this population; objective responses were observed in six patients (19%), with four confirmed partial responses and one unconfirmed partial response. Importantly, ARRY-520 demonstrated an 18% response rate (minimal response or better) in patients with MM refractory to both lenalidomide and bortezomib (i.e., dual-refractory MM). Furthermore, activity was observed in patients with high-risk cytogenetics.

[See link for table]

ARRY-520 was generally well tolerated, with only one patient (3%) discontinuing therapy for an adverse event. The most commonly reported adverse events were reversible, non-cumulative hematologic events; a low incidence of non-hematologic adverse events was observed, and no treatment-related events of neuropathy were reported.

ARRY-520 Shows Durable Responses in Patients with Relapsed/Refractory Multiple Myeloma in a Phase 1 Dose-Escalation Study (Abstract # 1860)
Presenter:Jatin J. Shah, M.D., Assistant Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center
This Phase 1, open-label, multicenter, dose-escalation study evaluated the safety, pharmacokinetics and pharmacodynamics of ARRY-520 administered intravenously (IV) on day 1 and day 2 repeated every 14 days in patients with MM. The study enrolled 31 patients with relapsed or refractory MM who had a median of six prior therapies and had received both a proteasome inhibitor and an immune mediated inflammatory disease (IMiD)-based regimen. The maximum tolerated dose (MTD) and the recommended Phase 2 dose for ARRY-520 was 1.50 mg/m2/day with G-CSF. ARRY-520 demonstrated an acceptable safety profile. Neutropenia was the most commonly reported adverse event and a low incidence of non-hematologic adverse events was observed.

ARRY-520 has shown clinical activity as a single agent in this heavily pretreated patient population. Objective responses were observed in four patients (13%), including three patients with partial responses. The partial responses were durable with a median duration of more than 8 months.

About Multiple Myeloma

According to the Multiple Myeloma Research Foundation, MM is an incurable blood cancer. The five-year relative survival rate for MM is approximately 34%, one of the lowest of all cancers. In 2011, more than 20,000 adults in the United States will be diagnosed with MM and approximately 11,000 people are predicted to die from the disease.

About KSP Inhibition

KSP is essential for cell division, or mitosis, in proliferating cells such as tumor cells. Prolonged inhibition of KSP arrests cells in mitosis, resulting in cell death. KSP inhibitors are novel anti-mitotics that specifically target proliferating cells and therefore may avoid some non-specific side effects, such as neuropathy. ARRY-520 has a mechanism of action distinct from current standards of care in multiple myeloma and is the only new drug with this mechanism of action that shows compelling single-agent activity in dual-refractory MM.

About ARRY-520

ARRY-520 is a potent, selective KSP inhibitor. The mechanism of action of ARRY-520 is distinct from other drugs in myeloma. ARRY-520-induced apoptosis requires loss of the survival protein MCL-1. Myeloma and other hematologic cancers depend on MCL-1 as a key survival protein. ARRY-520 has demonstrated durable single-agent activity in patients with dual-refractory MM, a population with significant unmet need. In preclinical studies of MM, ARRY-520 is highly active; regressions have been observed in bortezomib- and lenalidomide-resistant models and synergy has been observed when combined with bortezomib or lenalidomide. Combinations of ARRY-520 with other active agents may provide greater patient benefit, and offer extensive development opportunities in earlier lines of therapy. ARRY-520 is currently undergoing investigation in three combination clinical trials: ARRY-520 with dexamethasone in patients with dual-refractory MM, ARRY-520 with Velcade®(bortezomib) plus dexamethasone in patients with relapsed and refractory MM, and ARRY-520 with carfilzomib in patients with relapsed or refractory MM.

About Array BioPharma

Array BioPharma Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted small-molecule drugs to treat patients afflicted with cancer and inflammatory diseases. Array has four proprietary clinical programs: ARRY-614 for myelodysplastic syndromes, ARRY-520 for multiple myeloma, ARRY-797 for pain and ARRY-502 for asthma. In addition, Array has 10 partner-funded clinical programs including two MEK inhibitors in Phase 2: selumetinib with AstraZeneca and MEK162 with Novartis. For more information on Array, please go to www.arraybiopharma.com.