Analyst Conference Summary

conference date: August 4, 2016 @ 1:30 PM Pacific Time
for quarter ending: June 30, 2015 (second quarter 2016, Q2)

Forward-looking statements

Overview: Development stage company continues to make progress with its RNAi therapies. It is running deep in the red due to R&D expenses.

Basic data (GAAP):

Revenue was $8.7 million, up sequentially from $7.3 million, and flat from $8.7 million year-earlier. All revenue was from collaborations.

Net loss was $90.1 million, up sequentially from loss of $103.0 million, and down from loss of $71.8 million year-earlier.

Diluted EPS was negative $1.05, up sequentially from negative $1.21, and down from negative $0.85 year-earlier.

Guidance:

End of year cash will be greater than $1.0 billion.

Conference Highlights:

Has 10 clinical stage programs; 2 are in Phase 3. By year end that should be 12 and 3.

"We continue to advance our pipeline of now ten investigational RNAi therapeutics, an entirely new and innovative class of medicines, across a broad range of diseases. We believe our two latest stage programs, patisiran and revusiran, have demonstrated encouraging progress for patients with hATTR amyloidosis," said John Maraganore, CEO.

There will be data readouts from almost all of Alnylam's programs in the remainder of the year.

All revenue was from collaborators: $3.3 million from The Medicines Company, $5.4 million from Genzyme. Some of this revenue resulted from payments for milestones achieved.

Cash and equivalents balance at the end of the quarter was $1.28 billion, up sequentially from $1.21 billion. Added $150 million in long-term debt. Expects to end 2016 with over $1 billion cash balance.

Strategic program "Alnylam 2020" provides guidance for the commercialization of RNAi therapies through 2020, assuming the clinical data supports that. Expects to have 3 commercial products by 2020, with a robust follow-up pipeline of 10 clinical programs.

Patisiran Phase 3 APOLLO study for the treatment of hereditary TTR-mediated amyloidosis with polyneuropathy (hATTR-PN), also known as familial amyloidotic polyneuropathy (FAP), continued and presented baseline demographic data. Topline results should be available a little over a year from now.

Patisiran Phase 2 open-label extension study hATTR-PN data showed can "potentially halt or improve neuropathy progression."

ALN-PCSsc is partnered with The Medicines Company, which completed enrollment in a Phase 2 trial. ALN-PCSsc targets PCSK9 to treat hypercholesterolemia (high cholesterol). Results may support quarterly dosing. Initial Phase 2 ORION-1 data could be available in late 2016, with a Phase 3 start possible in 2017. More interim Phase 1 data showed continued positive results in Q2.

Revusiran Phase 3 ENDEAVOR study continued to enroll ATTR amyloidosis FAC (familial amyloidotic cardiomyopathy) patients. Enrollment should complete in late summer 2016 with data in 2018. Phase 2 OLE data for hATTR-CM 12 month data was reported showing sustained and clamped TTR KD out to 12 months with a mean max of 88%. 7 patients died, but deaths were unrelated to revusiran. We believe we will need the data from control studies to evaluate the effect of TTR knockdown on clinical outcomes.

Alnylam started a Phase 1 trial for ALN-TTRsc02, an ESC-GalNAc-siRNA conjugate targeting TTR for the treatment of ATTR amyloidosis, which is expected to enable a once-quarterly subcutaneous dosing regimen.

Fitusiran for hemophilia and rare bleeding disorders Phase 1 study interim results were positive, achieving a median estimated annualized bleeding rate of zero for hemophilia A and B. OLE study continued. Phase 3 studies should start in early 2017. Genzyme is a partner in the ALN-AT3 program, with goal of commercializing outside of U.S. and Europe.

ALN-AS1 for acute hepatic porphyrias reported initial Phase 1 data. Demonstrated potent, dose-dependent lowering of toxic heme intermediates that mediate attacks. A Phase 3 trial will be started in 2017. Granted Orphan Drug designation.

ALN-CC5 for complement-mediated diseases including PNH continued dosing in a Phase 1/2 trial after reporting positive initial efficacy and safety data. A new phase 2 PNH study should start in 2016. A phase 3 trial for aHUS and mysasthenia gravis could start in 2017. Could be used with or without eculizumab (Alexion's Soliris). Will also study in related diseases starting in 2017.

ALN-AAT for ATT deficiency liver disease continued a Phase 1/2 trial.

ALN-GO1 for primary hyperoxaluria type 1 (PH1) continued a Phase 1/2 study in Europe. It received Orphan Drug Designation from the FDA. There are about 5,000 potential patients worldwide. Preclinical data was published in the Journal of American Society of Nephrology.

ALF-F12 targeting factor XII is now in development for the treatment of hereditary angioedema and for thromboprophylaxis.

ALN-HBV Phase 1 study began. Initial data should be available in mid-2017.

See also Alnylam pipeline.

Operating expenses of $ million consisted of: $ million for research and development and $ million for general and administrative expense. Interest & other income was $ million. Income taxes $0 million. Unrealized loss on marketable securities was $ million.

Alnylam broke ground for a new manufacturing facility in Norton, Massachusetts.

R&D day will be December 16.

Q&A:

AS1 porphyria program timing of data presentation? Complete results from A and B on December 7 in Rome. Recurring attack patient data also at ASH pending abstract acceptance.

Norton plant CMC readiness for fitusiran? We will be ready to launch on the CMC side. Fitusiran drug substance is made by a third party manufacturer who will be agency inspection ready well before the launch. The drug product is being made by us in Cambridge. The Norton facility is for pipeline needs beyond fitusiran and should be operational in 2018.

The platform that allows for once quarterly dosing has helped create a very, very good safety profile. There have been very few subjects to drop out of studies.

Polyneuropathy trial cardio data in label? Many patients with ATTR amyloidosis have both polyneuropathy and cardiomyopathy. In the APOLLO study we saw about half with both. Hypothesis is TTR reduction should help both. We might see that in the APOLLO study, and if so we would want to bring it to the attention of regulators.

Wild type TTR? We do hope to address that larger market in the future.

HBV trial design? We have started the healthy volunteer part of the study. HBV has variants. Next year we will report data on the subtypes of HPV and also for patients who are receiving the antiviral standard of care. The initial data should show the degree and extent of antigen knockdown. But then we would need further trials with multiple doses to see if we can effect a cure, which would be more 2018.

Fitusiran beyond hemophilia? It is a broad based therapy that could be used beyond hemophilia, like thrombin deficiency disorders. They have high unmet need. We will begin to explore some of those targets as early as 2017.

Acute trauma surgery setting for fitusiran? We have good data for bleeds when on fitusiran. So we know you can combine factor with it safely. As the program goes on we will want to study the specific question you are asking. If necessary fitusiran's effects can be immediately reversed.

ALN-AAT for ATT deficiency liver disease? Beyond AAT knockdown the question is liver outcomes. There is liver elapsography. There are panels of fibrosis markers. Then biopsies that AAT knockdown might affect. We are looking at the full range of possibilities.

Good Hazard ratio for ALN-PCSsc in the current large scale PCSsc outcomes studies? There is good reason to be encouraged. As little as a 33% relative risk reduction would be an impressive result.

How much capacity will the Norton facility really have? We should be able to run multiple therapies in parallel. It does depend on doses and frequency. We can certainly run all the genetic diseases programs there.

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