- I am just starting to post my Alnylam notes on the $ALNY research page, but the stock is dirt cheap and I made my first buy on 6/9/11. If you factor in the imputed value of their stake in Regulus (based on Sanofi SNY investment fall 2010), ALNY sports a near zero enterprise valuation.
- See below the jump for my complete notes from the 5/25/11 webcast at the ThinkEquity conference:
- host analyst- 3 major upcoming milestones: 6/11 ASCO (VSP data), 3q11 (TTR RNAi POC), 4q2011 (PCSK9 p1 data)
- ALNY and others have made major recent achievements in delivery
- goal: build top tier bitoech company based on scientific excellence, IP, and business partnerhsips
- Time for RNAi is now b/c: 1) delivery breakthroughs 2) growing human experience; safety and predictable PK including systemic therapy 3) human RNAi proof of mechanism (derisking event for overall technology)
- ALNY's "5x15" (5 drugs in latestage development by end of 2015 excluding partner programs) strategy targets w/ common features:
- major unmet medical need
- genetically defined target and disease
- leverage existing delivery platform
- early biomarkers in p1 for human POC
- established, clinically relevant endpt for NDA w/ focused pt database
- potential for early commecialization paths
- 5x15 program #1) disease is ATTR (click here for background): 50k pt worldwide, onset ~40-60 yrs old, generally with cardiac and or neuropathy, fatal within 5-15 yrs
- caused by autosomal dominant mutations in TTR gene- over 100 defined, pathology caused by misfolded protein
- current SOC is liver trasplant but <3000 pts eligible
- currently in p1 w/ up to 36 pts, 4 countries in europe
- 3q2011: will report blood levels of TTR measured before and after therapy. key POC data
- 5x15 pgm #2) severe hypercholesterolemia
- 500k pts. LDL >200mg/dL, statins inadequate, at risk for early/recurrent/fatal MI
- about to start p1 2q2011, data by ye2011. showed analagous non-human primate data: Reduced psck9 blood plasma level, durable for weeks after a single injection, reduced LDL levels
- 5x15 pgm #3) refractory anemia- conditions inadequately controlled with use of EPO or IV iron, such as end stage renal disease, cancers including MDS and MM
- hepcidin target- central regulator of iron hemoestasis. downregulates ferroportin (reduced iron tranport to bone marrow. can monitor serum iron levels in p1.
- Anticipate IND filing 2012
- RSV01- p2b interim data 2012
- VSP- plan to partner before p2 (phase 1 data presented at ASCO, so anytime I guess)
- Huntingtin- Drug-device combo program partnered with Medtronic $MDT, currently in tox studies. IND/p1 2012
- by this time next year will have 5 pgms in clinic
- Delivery of RNAi: significant improve the dose level needed to achieve target KD in animals. LNP collaboration w/ Alcana
- new microfluidics technology (collaboration with Precision Nanosystems)- smaller LNP particle size- now can deliver to targets other than liver
- new conjugate delivery technology: Takes advantage of hepatocyte asialoglycoprotein receptor (ASGPR)...facilitates sub-cutaneous vs IV infusion administration. Single dose, get silencing for weeks
- 2011 guidance for ye2011 cash balance >$275m cash
- Expect to form additional partnerships 2011
- q&a session:
- Do you believe you need a companion diagnostic for TTR? No need.
- Do you expect certain TTR mutations to have different treatment response to TTR therapy? The drug candidate targets 3' UTR region which is absolutely conserved across all described mutant forms
- Endpoints in addition to TTR KD over time? Also measuring vitamin A, retinin protein binding, clinical features (but don't expect meaningful clinical outcomes)
- What level of KD needed for clinical benefit? Based on other amyloid diseases and liver transplant data: as little as 50% over time is sufficient for regression of amyloid deposition. Would hope to get doses giving 50-80% KD to advance into pivotal studies. Hope to achieve with TTR01, and certainly think it is achievable in TTR02 backup program with next generation LNPs
- Smaller particles- what other tissues would they reach? Current version is 70-90nm...similar physiologically to chylomicrons. Newer 20 nm resembles HDL- distreibute into all steroegenic organs in body
- Subcutaneous delivery program is advancing faster than would have thought and rapidly..but no date given for entering clinic
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