Replies to post #141058 on Biotech Values

[RockRat]

Any thoughts on Squarer & Holden? The BOD appointments look OK. Nereus, Dr. Holden's employer for the past 7 years appears to be dying a quiet death w/o getting anything beyond P2. Last clinical trial update, a completed P2 over a year ago. No PR in almost two years. Prior to that, they'd kick out 2 or 3 PRs per year. Makes me wonder about Holden's effectiveness these days. Or maybe he just hired into a company that turned out to have loser compounds, and there was nothing he could have done about it.

Has Squarer ever led anything resembling a development stage research boutique? Hospira and Array aren't too similar, and they're awfully vague about his prior career posts.

Regards, RockRat

[mcbio]

ARRY - 3Q12 CC notes

1. Reference to hiring Holden to assist with formulating regulatory strategy around ARRY-614. ARRY later indicated that they expect to start a registration study for 614 in 2013.

2. ARRY expects to start Phase 1 trials for ARRY-981 (targets GPR119 in type 2 diabetes) in last quarter of this year (not sure if fiscal or calendar). ARRY expects to begin partnering discussions very soon and expects any deal to have "significant value." (ARRY pointed to the $60M up-front deal it inked with AMGN for ARRY-403 after that drug's Phase 1 results.)

3. Kevin Koch pointed to the pending Phase 2 selumetinib KRAS NSCLC data as the real value driver for ARRY. He noted that KRAS NSCLC has very poor prognosis and is in dire need of new medical treatments. Koch also said ARRY is "very pleased" with the data and looks forward to the disclosure at ASCO. (FWIW, and perhaps absolutely nothing, Koch seemed more anxious than normal during planned remarks.)

4. Koch confirmed that we will have top-line Phase 2 data for selumetinib against BRAF melanoma this quarter (I was unsure by the vague wording in the quarterly results PR.)

5. ARRY included a milestone from AZN for commencing Phase 3 trials with selumetinib in its milestone guidance. ARRY thinks a Phase 3 trial for selumetinib against KRAS NSCLC would at least replicate the Phase 2 trial design but could also be more expansive. ARRY expects a formal announcement from AZN on whether or not it will commence Phase 3 trials with selumetinib either at ASCO or during the summer.

6. ARRY is looking for a 25% response rate from 520+dex and PFS around the 4 month mark in the ongoing trials.

[pcrutch]

Efficacy and safety of oral MEK162 in patients with locally advanced and unresectable or metastatic cutaneous melanoma harboring BRAFV600 or NRAS mutations.

Background:    BRAF and NRAS mutations occur in 50-60% and 15-20% of cutaneous melanomas, respectively. MEK162, a selective inhibitor of the kinases MEK1 and MEK2, has shown pre-clinical activity in BRAF and NRAS mutant (mt) melanoma models. This open label, phase II study assessed the antitumor activity of MEK162 in patients (pts) with BRAFV600 and NRAS mt advanced cutaneous melanoma. Methods:      MEK162 was administered orally at a starting dose of 45 mg twice daily. Treatment was until unacceptable toxicity, disease progression (PD) or investigator or patient refusal. Tumor response was assessed by CT imaging every 8 weeks (RECIST 1.0) until PD.

Results:      As of 16 Sept 2011, the full analysis and safety populations comprised 66 pts: 42 BRAF mt and 24 NRAS mt. Median age 58.0 years; 57.6% male; 72.7% WHO performance status 0. All NRAS pts and all but 2 BRAF (1 each stage IIIB and IIIC) pts had stage IV disease, and 87.5% of NRAS pts and 66.7% of BRAF pts had received prior therapy at study entry. Median time from 1st diagnosis to 1st dose of drug was 40.4 months. Median time on study was 10.4 and 8.5 weeks for the BRAF and NRAS arms. Relative dose intensities of 80–<100% were received by 71.4% and 70.8% of pts, respectively.

Among 29 BRAF mt and 13 NRAS mt pts evaluable for efficacy, 1 confirmed and 6 unconfirmed partial responses (PRs) and 9 pts with stable disease (SD) were recorded in the BRAF arm and 2 confirmed PRs, 1 unconfirmed PR and 4 pts with SD recorded in the NRAS arm.

Common treatment–related adverse events (AEs), all grades (Gs) and all pts, were rash (40.9%), diarrhea (33.3%), acneiform dermatitis (27.3%), creatine phosphokinase (CK) elevation (25.8%), fatigue (18.2%) and peripheral edema (21.2%). Central serous retinopathy-like retinal events (G 1/2 only) were reported in 8 (12.1%) pts (6 G1, 2 G2). All retinal events were reversible. G3/4 AEs in >1pt were diarrhea (4.5%) and CK elevation (15.2%). 5 pts discontinued due to toxicity. 34 pts are ongoing with more responses under current review.

Conclusions: MEK162 showed clinical activity and good tolerability in pts with BRAF and NRAS mt advanced melanoma. This is the 1st targeted therapy to show activity in pts with NRAS mt melanoma.

[mcbio]

ARRY - 4Q12/FY12 results

http://finance.yahoo.com/news/array-biopharma-reports-financial-results-201900964.html

Array BioPharma Reports Financial Results for the Fourth Quarter and Full Year of Fiscal 2012

Five Potential Phase 3 Decisions by the End of 2013

BOULDER, Colo.--(BUSINESS WIRE)--

Array BioPharma Inc. (ARRY) today reported results for the fourth quarter and full year of fiscal 2012.

Array reported revenue of $20.7 million for the fourth quarter of fiscal 2012, compared to revenue of $19.0 million for the same period in fiscal 2011. The Company recorded expenses of $14.9 million on proprietary research and development for the quarter to advance its clinical development and discovery programs, compared to $19.3 million during the same period last year. Array reported a net loss of $8.0 million, or ($0.09) per share, for the fourth quarter, compared to a net loss of $21.8 million, or ($0.38) per share, for the same period last year. Array ended the fourth quarter of fiscal 2012 with $90 million in cash, cash equivalents and marketable securities.

Array reported revenue of $85.1 million for the fiscal year ended June 30, 2012, compared to revenue of $71.9 million for fiscal 2011. Net loss for the fiscal year ended June 30, 2012 was $23.6 million, or ($0.33) per share, compared to a net loss of $56.3 million, or ($1.02) per share, reported in fiscal 2011. Array spent $56.7 million in proprietary research and development for the year, compared to $63.5 million for fiscal 2011.

Array is evolving into a late-stage development company, with two wholly-owned programs, ARRY-614 and ARRY-520, and three partnered programs, selumetinib partnered with AstraZeneca, MEK162 partnered with Novartis, and danoprevir, partnered with InterMune / Roche, having potential Phase 3 decisions by the end of calendar year 2013.

Array currently has ten drug candidates in Phase 2 clinical development, seven of which are funded through partnerships with global pharmaceutical and biotechnology companies. Over the next year, the company expects results from the following five clinical trials:

Phase 1 dose escalation trial for the new formulation of ARRY-614 in patients with myelodysplastic syndromes
Phase 2 combination trial for ARRY-520 plus dexamethasone in patients with multiple myeloma who are refractory to Revlimid® (lenalidomide), Velcade® (bortezomib) and dexamethasone therapy
Phase 1b combination trial for ARRY-520 plus Velcade in patients with relapsed or refractory multiple myeloma
Phase 2a trial for ARRY-502 in patients with persistent asthma
Phase 2a trial for AMG151 trial in patients with Type 2 diabetes
Ron Squarer, Chief Executive Officer of Array, noted, “We made great progress from a financial standpoint in fiscal 2012. We recorded a double-digit increase in annual revenue while managing our spending and strengthening our cash position. Looking ahead, we are evolving into a late-stage development company, moving towards multiple pivotal trials by the end of calendar year 2013.”

Mr. Squarer added, “We are excited about the recently announced Phase 2 clinical trial results for ARRY-797 which showed statistically significant pain reduction on top of NSAIDS compared to placebo plus NSAIDs in osteoarthritis patients suffering from moderate to severe knee pain. Remarkably, for patients who completed the trial, the level of pain relief demonstrated by ARRY-797, a non-opioid drug, was comparable with oxycodone ER, a proven, powerful opioid with significant tolerability and safety issues. The drop-out rate for oxycodone ER was more than five times greater than for ARRY-797. In addition, we remain confident that AstraZeneca and Novartis will continue development of selumetinib and MEK162, respectively, based on the potential these products hold for patients as demonstrated in their Phase 2 trials shared at ASCO.”

UPDATES ON KEY PROGRAMS

ARRY-797 – p38 inhibitor for pain: Array announced in July 2012 that ARRY-797, a non-opioid, met its primary endpoint in a randomized, placebo-controlled and active-controlled (oxycodone ER) Phase 2 clinical trial in 157 osteoarthritis patients suffering from moderate to severe knee pain despite the use of non-steroidal anti-inflammatory drugs (NSAIDs). Patients in all treatment groups continued using NSAIDs throughout the trial. ARRY-797 is a novel, oral, selective p38 inhibitor with a mechanism of action unique from that of currently approved pain medications.

Treatment with ARRY-797 resulted in a statistically significant reduction in pain over a 28-day period compared to placebo, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC®) pain subscale (a 0 – 10 numerical pain rating scale). Patients receiving ARRY-797 experienced a mean reduction in the WOMAC pain subscale score at day 28 vs. baseline that was 0.8 greater than those receiving placebo (2.4 vs. 1.6; one-sided p = 0.0247). Oxycodone ER was used as the active control for the trial and achieved improvement of 0.28 versus Placebo due to a higher discontinuation rate. ARRY-797 also showed improvement relative to placebo or oxycodone ER in additional measures including, WOMAC physical function, WOMAC stiffness and the Patient’s Treatment Satisfaction Measure. The discontinuation rate due to adverse events was higher in patients treated with oxycodone ER (34%) than for either the ARRY-797 (6%) or placebo (8%) treatment groups. In patients completing the trial, the reduction in WOMAC pain observed for ARRY-797 was comparable to that seen with oxycodone ER.

In this trial, ARRY-797 was considered overall to be well-tolerated at the selected dose of 400 mg twice-daily. The most common adverse events observed in patients treated with ARRY-797 were dizziness, diarrhea and nausea, which were mainly mild in severity. ARRY-797 treatment was associated with sporadic, transient increases in creatine kinase and aspartate aminotransferase. Mild prolongations of the QTc interval and sustained decreases in systolic and diastolic blood pressure were also observed. Given the scope of a development program in pain, Array will seek an appropriate partner to maximize the value of this drug.

ARRY-614 – Dual p38/Tie2 inhibitor for Myelodysplastic Syndromes (MDS): Array advanced ARRY-614 in a Phase 1 clinical trial in patients with MDS using an optimized formulation of the drug with improved plasma exposure and lower inter-subject variability. Array intends to meet with the FDA to discuss the development plan to support registration.

ARRY-520 – KSP inhibitor for Multiple Myeloma (MM): Array advanced ARRY-520 in three clinical trials:

1. Phase 2 trial in combination with dexamethasone in patients with MM refractory to Revlimid, Velcade and dexamethasone therapy

2. Phase 1b trial in combination with Velcade plus dexamethasone in patients with relapsed or refractory MM

3. Phase 1b investigator-sponsored trial in combination with Kyprolis® (carfilzomib) in patients with relapsed or refractory MM who are refractory or intolerant to Velcade therapy

Positive results in any one of these trials could define a path to late stage development.

ARRY-502 – CRTh2 antagonist for asthma: Array continued a Phase 2a trial with ARRY-502, a CRTh2 antagonist, in patients with persistent asthma. Array expects top-line results from this trial during the second quarter of calendar 2013 and intends to seek a partner for further development of ARRY-502 in this large- market disease indication.

Selumetinib (AZD6244) (AstraZeneca) – MEK inhibitor for cancer: Results for selumetinib in patients with KRAS mutation-positive NSCLC were presented in June 2012 at the American Society of Clinical Oncology (ASCO) annual meeting. This double-blind, randomized Phase 2 study showed statistically significant improvement in progression-free survival, objective response rate, and alive and progression-free at six months as well as longer median overall survival of 9.4 versus 5.2 months in favor of selumetinib in combination with docetaxel versus docetaxel alone. In addition, AstraZeneca initiated a bioequivalence trial comparing the current Phase 2 and planned Phase 3 capsule formulations. And Array expects results to be reported this year for the Phase 2 trial with selumetinib in combination with dacarbazine versus dacarbazine alone as first-line treatment in patients with BRAF-mutant melanoma.

MEK162 (Novartis) – MEK inhibitor for cancer: Novartis and Array are currently conducting eleven clinical trials, including two Phase 2 trials, three Phase 1b trials in combination with different PI3 kinase inhibitors, two Phase 1b trials in combination with different RAF inhibitors and one Phase 1b trial in combination with paclitaxel. Promising data on MEK162 in an ongoing Phase 2 trial of patients with BRAF and NRAS mutated advanced melanoma were presented at the ASCO annual meeting. In this trial, MEK162 showed clinical activity and good tolerability in patients with BRAF or NRAS melanoma. This is the first targeted therapy to show activity in patients with NRAS mutated melanoma.

OTHER DEVELOPMENTS

In July, Array received an $8.5 million milestone in its collaboration on AMG 151 with Amgen Inc. The milestone was achieved after Amgen reached a pre-defined patient enrollment level in a Phase 2a clinical trial in patients with Type 2 diabetes.
At the 2012 ASCO annual meeting, Genentech, a member of the Roche Group, presented results from a Phase 1b dose escalation trial showing that GDC-0068, an AKT inhibitor invented by Array scientists, was well-tolerated, when combined with Taxotere or mFOLFOX6, up to the single-agent maximum tolerated dose. Both combinations show evidence of clinical benefit, including in patients with PI3K/Akt pathway alterations and with prior taxanes or platinum agent treatment.
In April, Genentech initiated a Phase 1 trial with GDC-0575, a Chk-1 inhibitor Array licensed to Genentech, to evaluate multiple ascending-doses alone and in combination with Gemzar® (gemcitabine).
CONFERENCE CALL INFORMATION

Array will hold a conference call on Tuesday, August 14, 2012, at 9:00 a.m. eastern time to discuss these results. Ron Squarer, Chief Executive Officer, and Michael Carruthers, Chief Financial Officer, will lead the call.

Date: Tuesday, August 14, 2012
Time: 9:00 a.m. eastern time
Toll-Free: 800-561-2718
Toll: 617-614-3525
Pass Code: 62242246

Webcast & Conference Call Slides:
http://investor.arraybiopharma.com/phoenix.zhtml?c=123810&p=irol-irhome

A replay of the call will be available as a webcast on www.arraybiopharma.com

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 is evolving into a late-stage development company, with two wholly-owned programs, ARRY-614 and ARRY-520, and three partnered programs, selumetinib partnered with AstraZeneca, MEK162 partnered with Novartis, and danoprevir, partnered with InterMune / Roche, having potential Phase 3 decisions by the end of calendar year 2013. For more information on Array, please go to www.arraybiopharma.com.