This afternoon, investors, patient advocates, and the cancer research community get their first glimpse at clinical data from an RNAi therapeutic targeting polo-like kinase 1 (PLK1), in development by Tekmira Pharmaceuticals $TKMR. Preliminary phase 1 safety and efficacy data are being presented by Dr. Ramesh Ramanathan at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC.
Continue to the full post below for new,notes, and quotes from the 2012 year-end and 4q earnings call by Regulus Therapeutics RGLS, the microRNA company formed by Isis Pharma ISIS and Alnylam ALNY and which IPO'd in 2012.
Transcript from SeekingAlpha:
Earnings press release:
Following a joint venture spin-off from Alnylam ALNY and Isis Pharma ISIS, Regulus Therapeutics was born to focus on drug discovery using microRNA technology. Their 9/7/2012 revised S-1 filing revealed a planned price range $10-12 (but the offering was actually priced at $4 and Regulus now trades as ticker RGLS). Continue reading below for some highlights from the prospectus about the company and its research programs.
The race to developed novel cholesterol-lowering monoclonal antbodies targeting PCSK9 is heating up as Regeneron REGN and Sanofi SNY are the first to embark on a massive phase 3 program. While this battle is the realm of the big pharmas, small-cap biotech investors should also track the progress of these hypercholesterolemia drugs which are competitors in the familial HoFH/severe HeFH arena to KYNAMRO/mipomersen (developed by Isis Pharma ISIS with SNY - note Isis abandoned their PCSK9 antisense program), lomitapide (Aegerion AEGR), and ALN-PCS (RNAi against PCSK9 from Alnylam ALNY, which is seeking a parter for phase 2 development). Continue reading below the jump for the latest updates from 3q-2012 earnings conference calls about these candidates.
Alnylam $ALNY will present the following updated results related to their RNAi cancer program at #ASCO12 in June. Note that there is an unresolved patent dispute with Tekmira $TKMR around the IP covering this therapeutic.
Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy.
Maria Alsina, MD
Background: ALN-VSP02 is an RNA interference (RNAi) therapeutic comprised of lipid nanoparticle-formulated small interfering RNAs targeting vascular endothelial growth factor (VEGF)-A and kinesin spindle protein (KSP). In a phase 1 trial, ALN-VSP02 administered as an iv infusion q2 wks was well-tolerated and showed evidence of anti-VEGF pharmacology and antitumor activity.
Methods: Patients treated on the phase I trial with stable disease (SD) or better after 4 months (8 doses) were eligible to continue on an extension study until disease progression. Main objectives included continued evaluation of safety/tolerability and assessment of disease response.
Results: Seven of 37 patients (18.9%) evaluable for response went onto the extension study, including 1 of 7 (14.2%) at 0.4 mg/kg, 2 of 5 (40%) at 0.7 mg/kg, and 4 of 11 (36.3%) at 1.0 mg/kg. All had progressed after one or more prior therapies. Tumor types included head and neck squamous cell carcinoma, angiosarcoma, endometrial cancer, renal cell carcinoma (RCC, N=2), and pancreatic neuroendocrine tumor (PNET, N=2). At the time of enrollment, 6 had SD and one (endometrial cancer with multiple liver metastases) had an unconfirmed partial response (PR). The average length of time on treatment (including phase I and extension studies) was 9.5 months (range 5-19). As of January 2012, 3 patients remain on study, including the endometrial cancer patient with an ongoing PR who has had >80% tumor regression after 19 months of treatment at 0.7 mg/kg and two patients with RCC and PNET with continued SD after nearly 1 year of treatment at 1.0 mg/kg. The other patients with RCC and PNET at 1.0 mg/kg with SD came off after 8.5 and 5.5 months, respectively, for adverse events that included fatigue or elevated alkaline phosphatase. A decrease in spleen volume, likely an on-target effect and not associated with any adverse events, occurred to a greater degree on the extension study than on the phase I trial and was most pronounced in patients receiving ≥ 12 doses.
Conclusions: ALN-VSP02 has preliminary activity against endometrial cancer, RCC and PNET and a favorable safety profile that permits chronic dosing. Phase II trials are warranted in these and other VEGF-overexpressing tumors.
Alnylam $ALNY (click for research page) will present updates ALN-VSP phase 1 cancer data at ASCO - stay tuned for more details May 16th when abstracts are released.
Cubist $CBST continued to not mention their option to license ALN-RSV upon data expected mid-year 2012. ALNY also downplays this asset, so I think it is best to keep expectations low. Even if the data are good, I don't expect Cubist to opt-in and I don't expect ALNY to invest the resources to pursue the program alone.
ALNY is also trying to partner multiple preclinical and clinical programs, which the main focus being on their RNAi program directly against PCSK9 to lower cholesterol. We'll see if they can deliver.
Isis and Alnylam are each presenting data from research program at the AACR cancer research meeting next week. These are not related to current clinical programs, but shed light on potential future drug development efforts. See below for the full abstracts.
While Isis Pharma recently abandoned their PCKS9 antisense program, blaming regulatory concerns, other companies push forward with therapeutics against this important target, including Alnylam with a RNAi approach.
A more advanced program, from Sanofi $SNY and Regeneron $REGN, will release data this weekend at the American College of Cardiology Scientific Sessions. See below for the complete abstract. Note that this antibody was also featured in a recent New England Journal of Medicine article.
Presentation Number: 911-5
Abstract Title: The Effects of Co-administering a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease, REGN727/SAR236553, with 10 and 80 mg Atorvastatin Compared to 80 mg Atorvastatin Alone in Patients with Primary Hypercholesterolemia (NCT: 01288469)
Presentation Time: Sunday, Mar 25, 2012, 8:25 AM - 8:38 AM
Topic: 9. Prevention: Clinical
Author Block: Eli M. Roth, James McKenney, Corinne Hanotin, Gaelle Asset, Evan Stein, Sanofi-aventis US, Inc, Bridgewater, NJ, USA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA
Keywords: Hypercholesterolemia, Low‐density lipoprotein cholesterol
Background: Low-density lipoprotein cholesterol (LDL-C) reduction significantly lowers cardiovascular risk in at-risk patients. Atorvastatin 80 mg/day (A80) is a proven and highly efficacious LDL-C-lowering treatment. However, many patients do not achieve goals with maximal dose of statin. Proprotein convertase subtilisin/kexin 9 (PCSK9) binds to LDL receptors (LDLRs), increasing LDLR degradation and reducing the rate of LDL-C removal from the circulation. REGN727/SAR236553, a fully human monoclonal antibody, binds to PCSK9, enhances LDLR expression, and further reduces LDL-C levels in statin-treated patients. The primary objective of this study was to assess the LDL-C efficacy of high dose of A (A80) alone compared to both A 10 mg/day (A10) and A80 combined with subcutaneously (sc) administered REGN727/SAR236553.
Methods: This was a multicenter, double-blind, placebo-controlled study conducted in patients with hypercholesterolemia and LDL-C ≥100 mg/dL on A10 for ≥6 weeks prior to randomization to 3 parallel treatment groups: A80 + placebo (n=29), A80 + REGN727/SAR236553 sc every 2 weeks (q2w) (n=30), or A10 + REGN727/SAR236553 sc q2w (n=29). All patients were treated for 8 weeks and then followed for an additional 8 weeks.
Results: After 8 weeks of treatment, A10 + REGN727/SAR236553 patients had an additional [mean (SD)] LDL-C reduction of 66.7% (12.5), and those on A80 + REGN727/SAR236553 achieved a 72.3% (14.4) reduction, compared to a 17.7% (27.2) reduction in patients on A80 + placebo (p<0.0001). Significant reductions were also observed in apolipoprotein B, non-high density lipoprotein cholesterol and lipoprotein(a) with A80 + REGN727/SAR236553 versus A80 alone. Statistical comparisons with A10 were not performed. There was one serious adverse event of dehydration in the A80 + REGN727/SAR236553 group, which was deemed not treatment related. No other significant safety concern was observed.
Conclusions: Co-administration of REGN727/SAR236553 with A10 or A80 resulted in a significant and substantial decrease in LDL-C and was well tolerated.
I don't have the time to write a post about this transaction at the moment, but here is a collection of links related to this deal in the RNAi space (relevant to Alnylam ALNY):
Press Release (10/24/2011): "Arrowhead Research Corporation Acquires Roche RNA Assets and Site"
SEC filing form 8-k regarding the terms of this deal.
Transcript of conference call discussing the transaction.
Newspaper article with historical perspective.
Research White Paper by ARWR on RNAi Delivery - November 2011
For Perspective - June 2011 interview with ARWR CEO
I don’t typically do this, but there have been a flurry of press releases with news from companies I cover so below you will find quick comments on each: