I hadn't listened to Alnylam ALNY present in a few months so I listened to the recent Deutsche Bank presentation on podcast thanks to the tremendous Earningscast resource. A few very quick notes:
- ALN-TTR02 two-dose phase 2 in ATTR myopathy patients and ALN-TTRsc phase 1 (FAC patients) data should both be available within the next month or so - "middle of the year" for the phase 1 and a conference starting in late June for the TTR02 data.
- The ALN-TTR02 phase 3 trial would involve an as-yet undisclosed myopathy composite endpoint and a 12 or 18 month duration of treatment for the primary endpoint. Discussions on the protocol ongoing with both EMA and FDA. Overall would expect the trial to take 2.5-3.5 years to complete the trial with 150-200 patients.
- AT3 (hemophilia) IND should be submitted soon and start phase 1 this year with data in 2014, in patients.
- As I have been saying for ages, IV version of ALN-PCS is dead and the go forward product with The Medicines Co. MDCO with use the GalNac SC delivery system. CEO said that they haven't given guidance on when they will reenter phase 1, but said that if everything goes well they hope it could be "next year"
- Love the irony of how now that the Tekmira Pharma TKMR settlement is in the past, the LNP RNAi delivery technology is no longer "proprietary" and awesome, but is now stale leftover bread with no value proposition.
These notes are from memory - please correct via the comment section, email, or Twitter if I messed up or missed something important. Thanks in advance.
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.
For the moment, this will be the final installment of the BiotechDueDiligence AACR Annual Meeting preview..thanks for sticking with us. As always, see below for another collection of presentations from biotech companies covered on the website.
Preview Part 1 (SNTA, ASTX, NVS, INFI)
Preview Part 2
Preview Part 3 (ARRY, ASTX)
Preview Part 4 (ASTX, ARQL, BPAX)Preview Part 5 (TKMR, EXEL, PCYC, IMMU, VRTX)Preview Part 6 (CRIS INFI ISIS CLDX LGND PCYC)
In this post I will highlight some of the AACR Late-breaker abstracts that I am watching for, mostly related to clinical trial results. The big trials tend to be saved for ASCO in June, but there should be some interesting data nonetheless.Full coverage:
Preview Part 1 (SNTA, ASTX, NVS, INFI)
Preview Part 2
Preview Part 3 (ARRY, ASTX)Preview Part 4 (ASTX, ARQL, BPAX)
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. Abstract #3062 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.
1) LNP - robust for delivery to hepatocytes...perfected over years by many people/companies [subtle dig at TKMR who always claims to be most important in this]2) Conjugate - very excited about translating conjugate technology into pipleine as part of 5x15 as well [but first 4 of 5 programs announced use LNP...]Question and Answer session-
- Here are my quick notes from ALNY at Rodman and Renshaw 9/13/11:
- TTR: over 100 mutations described, our approach is to target all of these as well as wild-type protein [differs from Pfizer/FoldRx drug]
- 2 delivery approaches:
- Cash sufficient for a long time. We have given no specific guidance on runway. We will be partnering ex-US for these programs, and expect a lot of costs to be shared with partners. Goal is to build US commercial infrastructure... another reason to target orphan indications
- both LNP and conjugate particles are taken up by receptor mediated endocytosis (but via different receptors), both get access to cytoplasm via "leakiness"...this is an area of research and optimization
- We believe that executing on current business plan is right way to build shareholder value...vs M&A, inlicensing, etc. based on where our technology can go