Alnylam Pharmaceuticals, Inc. Q1 2010 Earnings Call Transcript

Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY)

Q1 2010 Earnings Call

May 05, 2010 4:30 pm ET


Cynthia Clayton - Senior Director of IR

John Maraganore - CEO

Barry Greene - President and COO

Akshay Vaishnaw - SVP of Clinical Research

Patty Allen - VP of Finance and Treasurer

Stuart Pollard - VP, Scientific and Business Strategy


Pamela Bassett - Cantor Fitzgerald

Simos Simeonidis - Rodman & Renshaw

Steven Willey - Thomas Weisel


Welcome to Alnylam Pharmaceuticals conference call to discuss the first quarter 2010 activities and financial results. (Operator Instructions)

I would now like to turn the call over to Alnylam.

Cynthia Clayton

I'm Cynthia Clayton, Senior Director of Investor Relations and Corporate Communications at Alnylam. With me today are John Maraganore, our Chief Executive Officer; Barry Greene, our President and Chief Operating Officer; Akshay Vaishnaw, Senior Vice President of Clinical Research; and Patty Allen, Vice President of Finance and Treasurer. In addition, Stuart Pollard, Vice President, Scientific and Business Strategy, is also on the call and available for Q&A.

During today's call, John will provide some introductory remarks and provide general context. Akshay will provide summary of our clinical and preclinical research and development activities. Patty will review our financials and guidance. And Barry will summarize our business highlights and goals. We will then open the call for your questions.

Before we begin, I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update any such statements.

I will now turn the call over to John.

John Maraganore

Welcome and thanks to everyone for joining us this afternoon. We had an extremely productive first quarter and a recent period of 2010 and are pleased to share with you today more details on the progress we have made as we continue to execute on our mission of building a top-tier biopharmaceutical company founded on RNAi. Specifically, we have remained very focused on the key value drivers of our business: scientific leadership, product pipeline, intellectual property and partnerships.

Our clinical pipeline continues to advance with the initiation of our Phase IIb trial with ALN-RSV01 in adults' lung transplantations, our Phase I trial with ALN-VSP in liver cancer and shortly our Phase I study with ALN-TTR in transthyretin-mediated amyloidosis. Indeed, together with our additional development stage programs and our advance in Regulus on microRNA therapeutics, this marks an extremely important time for the advancement of RNAi therapeutics.

We believe key clinical data will emerge over the next 12 to 24 months that will demonstrate and validate the opportunity for RNAi therapeutics as a whole new class of innovative medicines with broad potential to treat human disease.

This important progress in clinical translation is driven by the very significant advances we have made and that we recently reported on related to the delivery of RNAi therapeutics. As documented by recent papers and presentations, our advances in delivery are groundbreaking for the field and will have critical impact in our advancement of RNAi therapeutics to patients.

Overall, we continue to lead the field in the translation of RNAi into clinical studies and ultimately believe that we will beat the translation of these new medicines to the marketplace.

While our core focus remains on the advancement of RNA therapeutic products, we have also made important progress in our efforts with Alnylam Biotherapeutics, a new division of Alnylam focused on the application of RNAi technologies to transform manufacturing processes for biotherapeutic drugs by recombinant proteins and monoclonal antibodies, which together has defined about $100 billion market worldwide.

With Alnylam Biotherapeutics, we have an opportunity to expand and actually accelerate the applications of RNAi in medicine. And we're very excited about the impact that we expect this effort could have on Alnylam's overall business profile sooner rather than later. Akshay will expand on all of this progress in a moment, along with other notable achievements in our scientific leadership efforts.

Now on the business side, we demonstrated the continuous strength of our existing partnerships, having completed key technology transfer objectives with Takeda, resulting in a $20 million payment to Alnylam, announcing the receipt of a milestone payment from Roche related to their initiation of pre-IND studies for their most advanced RNAi therapeutic program, and Novartis' decision to exercise its right to purchase additional shares of Alnylam.

These are all very clear signs of extremely health relationships with great futures in front of them.

We're also pleased with the formation of a new collaboration between Regulus and GSK to develop and commercialize microRNA therapeutics targeting miR-122 for the treatment of HCV infection, an area of major unmet medical need. In the meanwhile, there remains significant interest across the industry for new alliances in RNAi therapeutics and also across our efforts at Regulus and Alnylam Biotherapeutics.

We are optimistic about forming new alliances in 2010. Of course, a critical component of all of this is the dominance of our intellectual property position that we continue to strengthen in 2010.

All told, the opportunity for RNAi therapeutics is a potential new class of innovative medicines is stronger than ever. And we believe Alnylam will continue to lead the advancement of this innovative technology towards patients. We look forward to continuing our progress throughout the rest of the year.

Now in closing, it shouldn't go without mention that Alnylam's success is driven by its people and our culture. In this regard, we were honored to be recognized by The Scientist magazine for the second year in a row as one of the top 10 best places to work.

With that, I'll now turn the call over to Akshay for a review of our clinical activities, our pipeline and our scientific progress. Akshay?

Akshay Vaishnaw

Thanks, John. As John mentioned, we made significant progress across our pipeline and scientific activity this past quarter.

In February, we initiated the Phase IIb multicenter globalized randomized double-blind placebo-controlled study of ALN-RSV01 in the adult lung transplant setting. This study was initiated based on the results from our previous clinical studies with ALN-RSV01, including the small Phase IIa study we completed and presented encouraging data on just last year.

The primary endpoint of the Phase IIb study is a reduction in instance of new or progressive bronchiolitis obliterans syndrome or BOS in RSV infected lung transplant patients. Secondary endpoints include assessments for safety and additional measurements of efficacy, including antiviral activity, recovery of lung function as monitored by the proportion of patients with recovery of lung function of greater than 80% of their pre-infection baseline and improvements in RSV symptoms as measured by cumulative daily total symptom score.

This trial will be performed in over 30 sites worldwide and aims to enroll up to 76 patients who we randomized in a one-to-one drug to placebo ratio. All patients will receive standard of care. And those receiving ALN-RSV01 with our drug administered as 0.6 milligram per kilogram dose by inhalation once daily for five days.

In parallel with the development of ALN-RSV01 for the treatment of RSV in lung transplant patients, Alnylam and Cubist are developing a second-generation compound, ALN-RSV02, which will be focused on the pediatric population.

Turning now to ALN-VSP, our program for liver cancer, enrollment is continuing in our Phase I multicenter, open label, dose escalation trial. This study is designed to enroll approximately 55 patients, primary and secondary liver cancer, with the primary objective being to evaluate the safety, tolerability and pharmacokinetics of intravenous ALN-VSP including demonstration of the maximum tolerated dose.

This is our first systemic RNAi program and also represents our first clinical program in an oncology setting. A double-digit number of patients have been enrolled across multiple-dose cohorts, and we expect to present preliminary data from the initial dose cohorts of Phase I trial at the 2010 ASCO Annual Meeting being held in Chicago next month.

Please note that this presentation will document our experience to date in initial dose cohorts in the trial, but is still actively enrolling into higher dose cohorts. So I would you urge you to bear this in mind.

Our ALN-TTR program for transthyretin-mediated amyloidosis or ATTR is also progressing well. ATTR is a hereditary systemic disease caused by mutation in the TTR gene. It's estimated to affect approximately 50,000 people worldwide and presents a tremendous unmet medical need with significant morbidity and mortality as an orphan disease. The only available treatment option for a small subset of these patients is liver transplantation. And historically, this has been an inadequate approach for the majority of patients.

And just a few weeks ago, we presented new preclinical data from our ATTR program at the International Symposium on Amyloidosis in Rome. These data showed that treatment with an RNAi therapeutic results in regression of preexisting pathogenic TTR deposits in peripheral tissues, significantly extending out previous data showing that ALN-TTR01 can prevent TTR deposition when administered in a prophylactic regimen.

These are really important new data that point to the breakthrough potential of RNAi therapeutics and underscore our continued excitement in this indication with our overall ALN-TTR program. In addition, preclinical data presented by some of our collaborators demonstrated the potential application of TTR-specific siRNA for the treatment of ocular disease in ATTR. We're looking forward to advancing ALN-TTR01 into its initial Phase I clinical trial in ATTR patients and remain on track to do so in the next couple of months or so.

Currently, we're in the process of finalizing an ethics committee approvals of clinical size in which the study will take place. Of course, empowered with our ALN-TTR amyloidosis, we're advancing a second-generation program ALN-TTR02 that utilizes our second-generation LNP platform.

We've also continued to advance important new development and preclinical programs, including ALN-PCS and RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia, and ALN-HTT and RNAi therapeutic targeting the huntingtin gene for Huntington disease, which we are developing collaboration with Medtronic.

We're encouraged by the advancements we've made in our preclinical studies on ALN-PCS using second generation LNPs, including the demonstration of durable and total reductions of PCSK9 protein levels and LDL cholesterol levels in non-human primates at very low dose levels.

Furthermore, Alnylam is advancing a number of additional preclinical RNAi and microRNA therapeutic programs, including ALN-HTT in collaboration with Medtronic for the treatment of Huntington's disease among several other RNAi therapeutic programs and a broad pipeline of microRNA therapeutics through our co-ownership of Regulus.

Also this past quarter, we advanced our platform for RNAi delivery with new publications and presentations of preclinical data describing some important progress. First, we've documented the discovery of second-generation LNP with markedly enhanced gene silencing potency with in vivo effects achieved at doses as low as 0.01 milligram per kilogram in rodents and non-human primates. In this regard, we're on track for even further improvements in potency on a trajectory that we believe will take us to the single microgram per kilogram dose level for gene silencing.

Second, we discovered an important mechanism for LNP-based delivery of RNAi therapeutic showing that endogenous ApoE mediates, the parasite delivery of LNP via ApoE receptors such as the LDL receptor, providing alternative potential approaches for delivery to non-hepatic tissues and cell types.

And finally, we showed some exciting new data documenting the delivery of RNAi therapeutics to immune cells, thereby continuing to broaden the clinical applications for RNAi beyond liver express disease targets.

As John mentioned earlier, our core focus remains on therapeutic applications of RNAi. Nevertheless, we also see important opportunities for RNAi technologies in other areas. An excellent example of this is our efforts with Alnylam Biotherapeutics, where we believe we can transform manufacturing processes for biotherapeutic drugs such as recombinant proteins and monoclonal antibodies.

We've been making important progress in our efforts here and just last month, we presented new results on the use of RNAi technologies for biotherapeutics manufacturing applications. In particular, our new data demonstrated the ability to use normal delivery lipids to achieve efficient delivery of siRNAs into Chinese hamster ovary or CHO cells grown in one liter suspension culture and the ability to achieve potent silencing of CHO host gene targets involved in cellular apoptotic and metabolic pathways.

With these data in hand, we're increasingly excited about utilizing RNAi technology to improve the quantity and quality of biologics manufacturing processes using mammalian cell culture such as CHO cells for exiting marketed drugs, also for new drugs in development and for the emerging by a biostimulus market.

For similar reasons, we're excited about our efforts in microRNA therapeutics and our efforts at Regulus. The lead program at Regulus is a microRNA therapeutic targeting miR-122 for the treatment of HCV infection an area of significant unmet need and where a host factor-based approach offers an important clinical differentiation to small molecule anti-HCV drugs emerging in development.

anti-miRs that target miR-122 have been shown to potently block HCV replication both in vitro and in vivo in a chimp model. And Regulus's developmental activities are focus on the selection of the clinical candidate but is expected to enter clinical testing in 2011.

Of course, in all of our efforts on our pipeline, on delivery and on new applications such as biotherapeutics manufacturing or microRNA therapeutics, our scientists distinguish themselves with excellence in leadership. Indeed, over the period scientists from Alnylam and Regulus demonstrated continued leadership with the publication of peer-reviewed scientific papers in some of the world's top journals such as Nature Biotechnology and PNAS and scientific presentations at high quality scientific forms.

Many of these accomplishments are highlighted in further detail in our press release we issued this afternoon.

And with that, I'll now turn the call over to Patty for review of the first quarter 2010 financials.

Patty Allen

I'll keep my comments brief and I urge you to look at our quarterly release for additional detail. I am happy to repot that we continue to maintain a solid financial position one in which our net cash position ranks in the top 15 across the entire biotech industry, allowing us to prudently invest in value creation for our business without the need to access the capital market for the foreseeable future.

At the end of the first quarter, Alnylam had cash, cash equivalence and total marketable securities of $419.3 million and zero debt.

We also continue to have no write offs related to our cash and fixed income portfolios to-date. Our GAAP revenues for the first quarter of 2010 were $24.6 million, keeping us on track for another $100 million revenue year for 2010.

As you know, the continued amortization of upfront payment from the strategic alliances we have formed with Roche and Takeda account very significant and recurring portion of our quarterly GAAP revenues including our recent milestone payments from Roche and Takeda.

On the expense side, I will make my comments this quarter, comparing the current quarter as compared to Q4 last year, which I believe is more informative. R&D expenses were $24.7 million in the first quarter of 2010 as compared to $21.6 million in Q4 of 2009.

The increase in R&D expenses includes expenses associated with the start of the ALN-RSV01 Phase IIb clinical trial in adult lung transplant patients, which began enrolling patients in Q1. The increase in R&D expenses is also a result of an increase in non-cash stock based compensation this quarter.

G&A expenses were $11.2 million in the first quarter of 2010 as compared to $13.1 million for Q4 of 2009. The decrease in G&A expenses in the first quarter is primarily a result of lower professional service fees, primarily related to legal activities as there were significant efforts in Q4 2009 related to our litigation.

In addition, last week we are happy to announce that Novartis selected to exercise their options to purchase additional shares of Alnylam in accordance with their 2005 agreement. Novartis purchased approximately 55, 000 newly issued shares of our common stock at $17.99 per share based on the contractual calculation of the 20 day trading average ending March 30, 2010 and resulting in proceeds to the company of about $1 million.

This is the maximum amount of primary shares that Novartis can purchase from Alnylam under our agreement at this time, whereby annually they have the right to settle up and maintain their current ownership level of approximately 13.4% of our common stock.

We will report the proceeds from this transaction in the second quarter. This is the third year in row that Novartis has elected to exercise this option and we certainly view this as a strong vote of confidence in our collaboration and our technology.

With respect to guidance for 2010, we continue to accept our cash position at the end of the year to be greater than $325 million excluding the potential payment from Novartis, should they decide to execute their adoption license later this year.

This concludes the financial highlights and I'll now turn the call over to Barry.

Barry Greene

As John mentioned earlier, our existing major partnerships are stronger than ever and remain a key driver of future value creation. For instance, our partnership with Takeda has been extremely productive. This past quarter, we were pleased to earn an additional $20 million technology transfer payment form Takeda as part of the strategic alliance we formed with them in May, 2008.

This payment is related to the achievement of certain predefined objectives and the transfer of our RNAi therapeutics platform technology and intellectual property to Takeda for their development of RNAi therapeutics. Today, we have received $140 million in upfront and technology transfer payments from Takeda and remain eligible to receive an additional $10 million in near term technology transfer payments.

And of course, we remain eligible to receive significant downstream milestones in royalties as programs advance. We also further advanced our 2007 landmark alliance with Roche.

In January, Alnylam announced a milestone payment from Roche related to the initiation of pre- IND studies for a Roche, RNAi therapeutics product candidate that Roche has guided will start clinical testing this calendar year.

Lastly, Regulus Therapeutics, our joint company with Isis focused on microRNA therapeutics, forming new strategic worldwide collaboration with GlaxoSmithKline to develop and commercialize microRNA therapeutics targeting miR-122 for the treatment of HCV infection.

This new HCV collaboration includes a $150 million in upfront and milestone payments in addition to royalties, as the two companies aim to advance microRNA therapeutics targeting miR-122 towards a clinic in 2011. This new alliance is a collaboration that furthers the previous GSK Regulus alliance, formed in 2008, around the discovery and development of microRNA therapeutics focused on immuno-inflammatory diseases.

As you can see, we continue to enjoy significant value from our existing partners and remain confident that we'll form new alliances in 2010 and beyond. Now, these alliances could include platform alliances like we have with Takeda and Roche. Product alliances such as those we formed with Medtronic, Kyowa Hakko and Cubist, alliances with Regulus therapeutics, Alnylam Biotherapeutics as well as new business ventures.

All of our existing alliances and the new ones that we form will continue to define Alnylam's business strategy in an extremely differentiated manner where our ability to advance our medicines and technologies to the market, and to build Alnylam can occur without the typical shareholder illusion that occurs historically in biotech. We believe that this will serve our shareholders very well over the medium and long-term.

Now, moving on to the key foundation of Alnylam, our international property, we continue to strengthen our IP estate, which includes issued allowed or granted fundamental patents in many of the world's major pharmaceutical markets. We've made important additions to our IP estate as detailed in our release today. Thus for in 2010, we have 17 new patents issued or granted in countries around the world, putting us well on track to meet our goal of 30 or more patent grants in 2010.

Now, in addition to enabling the industry to develop RNAi therapeutics, we believe that our patents and technologies must be made available for applications in the discovery of new medicines for neglected diseases in the world's poorest countries. In this regard, we've donated our IP and technology on a non-profit basis joining GSK in a Pool for Open Innovation established in 2009 and administered by BVGH.

We're very pleased to have just announced two new participants in the pool namely the Massachusetts Institute of Technology, one of the world's foremost academic research institutions and the South Africa's Technology Innovation Agency or TIA. MIT is the first academic institution to join Alnylam and GSK in providing patents to the Pool for Open Innovation.

And TIA becomes the first governmental agency to participate in the pool. We're absolutely thrilled with the additional participants taking part in this critical initiative and we look forward to additional participation from other companies, institutions and governments.

Overall, our IP continues to remain unparalleled in the industry and we're extremely confident that it is needed for the development and commercialization of all RNAi therapeutics.

Now, to review our goals over the next 12 to 18 months, we intend to have four RNAi therapeutic programs in clinical development and advance additional pre-clinical RNAi and microRNA therapeutic programs, including proprietary pipelin programs and partnership lease programs.

We continue advancing and developing novel delivery solutions for the systemic delivery of RNAi, an area we've made extreme progress in the last year. We intend to form new alliances in 2010 across our efforts at Alnylam, Regulus and through our Alnylam Biotherapeutics initiative for which we see near-term potential for value creation. We're going to further strengthen our scientific leadership in intellectual property position.

And lastly, finish 2010 with greater than $325 million in cash, which excludes the potential payment from the Novartis, should they decide to execute their adoption license later this year.

In summary, we at Alnylam are incredibly well positioned to be leading the transformational applications of RNAi to treat the severe diseases and create significant and positive impact on the lives of patients.

With that I'd like to turn the call back over to the operator for your questions. Ann?

Question-and-Answer Session


(Operator Instructions) And our fist question comes from the line of Pamela Bassett.

Pamela Bassett - Cantor Fitzgerald

Congratulations on all the new progress. Will you expand on the business strategy for Biotherapeutics, what kind of relationships you might establish? And even what those sales might look like? And can you also talk more about any more detail about specific characteristics that you might be able to impart that would drive value for manufacturers. And how RNAi would physically be used, or I should say at siRNAs?

John Maraganore

Let me answer that, and then maybe Stuart can also chime in here, as he's here and he's leading up that effort as you know. So there really are three categories of product offerings that we believe M&A from the Alnylam Biotherapeutics (separate).

One our products that we believe are broadly applicable for generalized DEXA biologics manufacturing, and these include products that are targeting product pathways or products that are targeting glycosylation pathways that are well understood to be, I'll call them, more generic aspects of challenges within the Biotherapeutics industry.

Then there are specific agreements that we will form on a company-by-company and even product-by-product basis with companies around the specific use of our technology for what I'll call generally idiosyncratic aspects of the biologics manufacturing related to what they're doing.

And this could be related to specific problems or challenges or new attributes that they want to engender within their products. And then finally there are our flat out license agreements that we can form, based on the technology that are essentially broad, and specific licenses to elements of our intellectual property and technology as it relates to the Biotherapeutics marketplace.

And so it's really those three different product offerings, Pamela, that we envisage will be operative. And there's quite a bit of interest across the industry on what we're doing here. And I think we're very heartened by the strong response that we've gotten by many people within the established Biotherapeutics marketplace.

I can't comment right now, because it'd be, obviously we had some clear ideas in house. But I'm not going to comment right now on how we would structure these agreements; I'll leave that to the nature of how these discussions progress. And obviously, you'll hear more about that in the not too distant future we hope.

But I can say that, these will be attractive opportunities for Alnylam, because it not only relates to products that are clearly in development stages within the Biotherapeutics marketplace. But also products that are current marketed. And this I think, create some opportunities here for Alnylam, which is significant.

Stuart, you want to elaborate any further on that point.

Stuart Pollard

No. I mean, I think just in terms of the application, Pamela, there are many processes that are impactual to successful manufacture of biologics where to stress apoptosis, secretion, metabolic processes. And the extraordinary parleying how you can interrogate and modulate all of those pathways that are singularly or in a multiplex manner.

In terms of how it's used, it would be used as a supplement into the media feed and non-genetic manipulation of the cells and that offers a completely new way and also (inaudible) whether interrogating these processes to the current processes, you've really only got crude manipulations like temperature pH et cetera. And you're essentially doing that to alter the behavior of the cells.

And here we can use RNAi to do that at will in an exclusively potent manner. And I just amplified John's comment, that we've really been very encouraged by the very robust response to the announcement of this initiative back in November of last year at our R&D day. And it gives us a real opportunity; we think the application could be quite near term. And applying this to the manufacturing of what is a very large market, as we refer to the $100 billion market today worldwide and growing very significantly.

John Maraganore

And importantly, Pamela just to close out the answer here to that question, this is transformative technology in this context. And so it really does become a game changer in terms of how people look at biologics manufacturing. And that's an important element of what RNAi has consistently shown itself to deliver.

Pamela Bassett - Cantor Fitzgerald

What would be the regulatory implications for manufacturers with products that are already launched or well underway in a clinical development? Do they have to make difficult modifications to their CMC, or additional filings or does the transient nature of these types of treatments make a smooth regulatory path in someway?

Barry Greene

As you rightly mentioned, this is a settlement of the media which there is clear precedent with things like protein agonist and it would be for approved products we believe supplementary BLA that would be required. If it's applied to a product in development, it would be integral to the BLAs as it goes forward.

John Maraganore

And that absolutely is how we look at it and how we believe it will play out. But I do want to emphasize that we have not had discussions with the FDA yet on this approach. And so that ultimately will be pressure-tested in its final determinant, but we're very confident that this is an approach that is consistent with other types of strategies and biologics manufacturing that's typically supported by a supplemental BLA.


And our next question comes from the line of Simos Simeonidis with Rodman & Renshaw.

Simos Simeonidis - Rodman & Renshaw

The TTR trial that you said you're going to start in a couple of months, could you please remind us of the size of the trial, how many slides you think you're going to use and also U.S. versus ex-U.S.?

Akshay Vaishnaw

So I think we're making good progress with our TTR efforts, as you have heard the call. Dosing will begin in the next couple of months or so. And I think at that time, we'd be happy to share a lot more with you in terms of some of the issues you raised. But suffice it to say, TTR-related disorders are found in certain geographic territories. We've talked about them before, places like Portugal, Sweden, et cetera. And so you'll see that our strategy is highly adjuvant to those observations.

Barry Greene

And I think just one important point I'll add to Akshay's response, Simos, of course, to be clear on the phone, the Phase I study will be in patients.

Simos Simeonidis - Rodman & Renshaw

I believe you're using two siRNAs in TTR01, the wild type and the mutant if I'm correct.

Barry Greene

No, we have one single siRNA that actually is cross-reactive with all mutant forms that have been described, as well as the wild type protein. So we can achieve that with one siRNA.

Simos Simeonidis - Rodman & Renshaw

Is there a mass model of TTR? When you're not going to have the wild type TTR genes what happens? Do you know that?

Barry Greene

There is a model of TTR amyloidosis, which as you know we recently reported some data on where we've shown both prevention of TTR pathogenic deposition in tissues as well as regression of TTR deposition. But regarding the knockout mouse, Akshay?

Akshay Vaishnaw

So the knockout mouse was probably sometime ago and is essentially a phenotype-less, Simos. So that has been amongst the many other reasons behind that need, our ability to target those wild type and mutant, et cetera. This was one of the attractions to this target that even people entirely deficient in this would not be expected to have any significant phenotype.

Simos Simeonidis - Rodman & Renshaw

And a quick question on the RSV front. Can you give us an update on the enrollment, and if not, maybe a projection about the completion of enrollment or one who we can expect to see data?

Barry Greene

I think it's too soon to give you any completion day timing. As you know, the study just got started up in early March, late February, and is actively accruing sites. We have multiple patients, many patients in this study at this point in time. We're just opening up sites in the southern hemisphere right now. We're sort of transitioning, as you know, between seasons in the north and the south.

And we'll certainly give you an update on timing or expected timing of completion, but this is too soon to do so in a way that is reliable to count on. But we are very pleased with how it's going. And the investigator interest and already the patient accrual has gone into it. We find it to be very encouraging. And stay tuned; we'll give you some more information as we get some more data.

Akshay, do you want to add anything more?

Akshay Vaishnaw

No, I think you've captured it.


(Operator Instructions) And our next question comes from the line of Steven Willey with Thomas Weisel.

Steven Willey - Thomas Weisel

Just quickly here on the liver cancer front, have you disclosed how many dose cohorts there are in the Phase I trial with respect to where you guys start with dosing or you end up in maybe just a number of patients that we're going to see in each cohort?

Barry Greene

Right, we haven't yet, but that will be presented relatively soon at ASCO. Obviously, there is an abstract that you'll see before ASCO, as you know, but we'll update with more data at the actual presentation for ASCO. But we haven't disclosed that as of yet. And given that it's only a few weeks away, I would just urge you to stay tuned for a couple of weeks. But we are in now multiple-dose cohorts with double-digit numbers of patients in the study.

Steven Willey - Thomas Weisel

And then with respect to the ability to demonstrate tumor-specific knockdown or target RNAi, I know that there was some excitement obviously around the (inaudible) data in melanoma. And I was wondering if there'll be anything within the presentation itself where you biopsy, maybe look at some of the tumor-specific knockdown of either VSP or --?

Barry Greene

We're going to provide all the data that we have available to us at the time of the ASCO presentation. And as we commented before, the primary endpoint of the study is establishing MTD and pharmacokinetics of the drug, but we're also collecting a number of other samples or are looking for signs of clinical activity. And these include things like the biopsy samples you're referring to, but also MRI-based measurements for antiangiogenic effects in a DCE-MRI, as well as traditional radiographic measurements for tumor response rates.

And so all of that will be made available when the posters present it. But bear in mind this is just the initial experience in the initial dose cohorts of the study. And so people should gauge their expectations accordingly.

Steven Willey - Thomas Weisel

And then I believe, Barry, you mentioned some possibility of near-term potential for value creation with respect to some of the biotherapeutic applications. Is it kind of safe to assume that some of those initial value-creating opportunities would be more predicated on, I guess, yields improvements and not necessarily manipulating a cell line, so that you're getting different glycosylation patterns?

Barry Greene

I would say that we're having all those type of discussion as we speak. In other words, the answer will be yes.


Ladies and gentlemen, this concludes today's question-and-answer session, and I would now like to return the call back over to Alnylam for closing remarks.

John Maraganore

Again, as you can tell, we're really excited about all the advances we've made in 2010 so far and look forward to updating you on our continued progress throughout the rest of the year. Stay tuned. Bye-bye.


Ladies and gentlemen, we thank you for your participation in today's conference. This concludes the presentation and you may now disconnect. Have a good day.

Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to All other use is prohibited.


If you have any additional questions about our online transcripts, please contact us at: Thank you!