Alnylam Pharmaceuticals Inc (ALNY) 2010 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals conference call to discuss the first quarter 2010 activities and financial results.

There will be a question-and-answer session to follow. Please be advised that this call is being taped at the Company's request.

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

Good afternoon. 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, 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 a 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 provision 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 such statement.

I will now turn the call over to John.

Thanks, Cynthia.

Welcome and thanks to everyone for joining us this afternoon. We had an extremely productive first quarter and 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 remain 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 RCL1 in adult lung transplantations, our Phase I trial ALN PSP in liver cancer, and shortly our Phase I study with ALN TTR in transplant remediated amloy doses.

Indeed, together with our additional development stage programs and our efforts at 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 have recently reported on related to the delivery of RNAi therapeutics.

As documented by recent papers and presentations, our advances in delivery are ground breaking for the field and will have critical impact in our advancements 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 lead the translation of these medicines to the marketplace. While our core focus remains on the advancement of RNAi therapeutic products, we've 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, like recombinant proteins and monoclonal antibodies, which together define 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 continued 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 for preIND 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 healthy 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 micro RNAi therapeutics targeting miR-122 for the treatment of HCV infections, 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 as 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 ten 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?

Thanks, John.

As John mentioned, we made significant progress across our pipeline and scientific activity this past quarter. In February, we initiated a Phase IIb multi-centered globalized randomized double blind placebo control study of LNR sphere I in the adult lung transplant setting. This study was initiated based on the results from our previous clinical studies LNR sphere I, including the small Phase II A study we completed and presented encouraging data on just last year. The primary end point of the Phase IIB study is a reduction in instance of new or progressive bronchiolitis obliteran syndrome or BOS in RSV infected lung transplant patients. Secondary end points include assessments for safety and additional measurements of efficacy, including anti-viral activity, recovery of lung function as monitored by the proportion of patients with recovery of lung function of greater than 80% of their preinfection baseline, and improvements in RSV symptoms as measured by cumulative daily total symptoms score.

This trial will be performed in over 30 sites worldwide and aims to enroll up to 76 patients who will be randomized in a one to one drug to placebo ration. All patients will receive standard of care and those receiving LNR sphere I will have drug administered at 0.6-milligram per kilogram dose by inhalation once daily for five days. In parallel with the development of LNR sphere I for the treatment of RSV in lung transplant patients, Alnylam and Cubist are developing a second generation compound, LNR sphere II, which will be focused on the pediatric population.

Turning now to our LNVSP, our program for liver cancer, enrollment is continuing in our Phase I multi-center, open label dose escalation trial. This study is designed to enroll approximately 55 patients with primary and secondary liver cancer, with the primary objective to evaluate the safety, tolerability, and pharmacokinetics of intravenous LNVSP, including a demonstration of the maximum tolerated does. 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 the 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 a trial that is still actively enrolling into higher dose cohorts, so I would urge you to bear this in mind.

Our LNTTR program for transthyretin-mediated amyloidosis or ATTR is also progressing well. ATTR is a hereditary systemic disease caused by a 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. 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 pre-existing pathogenic TTR deposits in peripheral tissues, significantly extending our previous data showing that can LNTTR01 can prevent TTR deposition when administered in a prophylactic regimen. These are really important new data that point to the breakthrough potential for RNAi therapeutics and underscore our continued excitement in this indication with our overall LNTTR program. In addition, preclinical data presented by some of our collaborators demonstrated the potential application of TTR specific SRNA for the treatment of an ocular disease--treatment of ocular disease in ATTR. We're looking forward to advancing LNTTR01 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 ethics committee approvals at clinical sites in which the study will take place. Of course, in parallel with our LNTTR01 efforts, we're advancing a second generation program LNTTR02 that utilizes outside cogeneration LMP platform. We've also continued to advance important new development and preclinical programs including LMPCS and RNAi therapeutic targeting PCSK9 for the treatment of hypocholesterolnemia. And LNHTT, and RNAi therapeutic targeting the Huntington gene for Huntington's disease, which we're developing in collaboration with Medtronic. We're encouraged by the advancements we have made in our preclinical studies of LMPCS using second generation LMPs, including the demonstration of durable and potent 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 microtherapeutic programs, including LNHGT in collaboration with Medtronic for the treatment of Huntington's disease among several other RNAi therapeutic programs and a broad pipeline of microtherapeutics through co-initiative 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 documented the discovery of second generation LMPs with markedly enhanced gene silencing potency, with (inaudible) 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 LMP based delivery of RNAi therapeutics showing that indigenous APOE immediates the parasite delivery of LMP via APO receptors such as the LDL receptor; providing alternative potential approaches for delivery to non-impatic tissues and (inaudible). 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 the recombinant proteins and monoclonal antibodies. We've been making important progress in our efforts here and just last month, we presented new results from the use of RNAi technologies for biotherapeutics manufacturing applications. In particular, our new data demonstrated the ability to use novel delivery lipids to achieve efficient delivery of SRNAs into Chinese hamster ovary, or cho cells grown in one liter suspension culture. And the ability to achieve potent silencing of cho hosting targets involved in cellular aptotic and metabolic pathways.

With these data in hand, we're increasingly excited about utilizing RNAi technologies to improve the quantity and quality of biologics manufacturing processes using mammalian self-culture, such as cho cells. For existing marketed drugs, also for new drugs in development, and for the emerging biosimilars market. For similar reasons, we're excited about our efforts in micro-RNA therapeutics and our efforts at Regulus. The lead program at Regulus is a micro-RNA 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 and to HCV drugs emerging in development. Antimir is target miR-122 have been shown to potently block HCV replication both in vitro, and in vivo in a chimp model. And Regulus' developmental activities are focused on selection of a clinical candidate that is expected to enter clinical testing in 2011.

Of course, in all of our efforts in our pipeline on delivery and on new applications such as biotherapeutics manufacturing or micron 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 forums. Many of these accomplishments are highlighted in further detail in our press release we issued this afternoon.

With that I'll now turn the call over to Patty for a review of the first quarter 2010 financials.

Thanks, Akshay and good afternoon, everyone.

I'll keep my comments brief and I urge you to look at our quarterly release for additional detail. I am happy to report 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 markets for the foreseeable future. At the end of the first quarter, Alnylam had cash, cash equivalents, 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 portfolio 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 up front payments from the strategic alliances we have formed with Roche and Takeda account for a 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 were happy to announce that Novartis elected to exercise their option 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 a 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. Where biannually, they have the right to settle up and maintain their current ownership level of approximately 13.4% of our common stock. We will record the proceeds from this transaction in the second quarter. This is the third year in a 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 expect 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.

Thanks, Patty and good afternoon, everyone.

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 from 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. To date, we have received $140 million in upfront and technology transfer statements 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 and 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 preIND 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 micro RNAi therapeutics formed a new strategic worldwide collaboration with GlaxoSmithKline to develop and commercialize micro RNAi therapeutics targeting miR-122 for the treatment of HCV infection. This new HCV collaboration includes $150 million in upfront and milestone payments in addition to royalties. As the two companies aim to advance micro RNAi 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 micro RNAi therapeutics focused on immunoinflammatory diseases.

As you can see, we continue to enjoy significant value from our existing partners, and remain confident that we will 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, 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 dilution 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 a key foundation of Alnylam, intellectual 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 far 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 patented 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 have donated our IPN technology on a nonprofit basis joining GSK in a pool for open innovation established in 2009 and administered by BVGH. We were 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 African 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 preclinical RNAi and micro RNA therapeutic programs, including proprietary pipeline programs and partnership based programs. We continue advancing and developing novel delivery solutions for the systemic delivery of RNAi, an area we've made extreme progress in 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 and intellectual property position. And lastly, finish 2010 with greater than $325 million in cash, which excludes the potential payment from 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?

Thank you. (Operator Instructions)

And our first question comes from the line of Pamela Bassett. Please proceed.

Hi. Thanks for taking my questions.

Hi, Pamela, how are you?

I'm fine, thanks. And you?

Excellent.

Good. 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 deals 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?

Sure.

I should say SIRNAs.

Yes. Fine. Let me answer that and maybe Stuart can also chime in here because 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 emanate from the Alnylam Biotherapeutics effort. One, are products that we believe are broadly applicable for general aspects of biologics manufacturing and these include products that are targeting apotactic pathways or products that are targeting bicostolation 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 by product by product basis with companies around the specific use of our technology for what I'll call a 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 flat-out license agreements that we can form based on our 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 envision will be operative; and there's quite a bit of interest across the industry, 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 biotherapeutics--established biotherapeutics marketplace. I can't comment right now because it would be--obviously we have 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.

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 frankly currently marketed; and this I think, creates some opportunities here for Alnylam, which is significant.

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

No. I think just in terms of the application, Pamela, there are many processes that are impactful on the manufacture--successful manufacture of biologics were it stress, apoptosis, secretion, metabolic processes, and the extraordinary power of RNAi, you can interrogate and modulate those--all of those pathways that are singularly or in a multi-plex manner.

In terms of how it's used, it would be used as a supplement into the media feed in a nongenetic manipulation of the cells. And that offers a completely new way and almost a rapier-like way of interrogating these processes. The current processes, you've really only got crude manipulations like temperature, PH, etc. And you're essentially doing that to alter the behavior of the cells, and here we can use RNAi to do that at will and in exclusively potent manner.

I'd just amplify John's comment that we've really been very encouraged by the very robust response to the (inaudible) 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 in applying this to the manufacturing, what is a very large market as we referred to $100 billion market today worldwide and growing very significantly.

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.

What would be the implications, the regulatory implications--thank you for going through all that--the regulatory implications for manufacturers with products that are already launched or well underway in their 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--smooth the regulatory path in some way?

Pamela, excellent question.

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

That absolutely is how we look at it and how we believe it will play out. 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 in biologics manufacturing that's typically supported by supplemental BLA.

Okay. Great. Thanks very much.

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

Hi, guys, thanks for taking the question.

Thank you, Simos. Good afternoon.

Hi.

The TDR trial that you said you're going to start in a couple months, could you please remind us the size of the trial, how many sites do you think you're going to use and also US versus ex-US?

Let me let Akshay go ahead and answer that directly.

Hi, Simos. I think we're making good progress with our TTRF as you heard during the call. Dosing will begin in the next couple of months or so and I think at that time we would 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 talked about them before, places like Portugal, Sweden, etc., and so you'll see that our strategy is highly atune to those observations.

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

Right.

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

No, we have one single SRNA 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 SRNA.

Okay.

Is there a mass model of TTR, and I'm trying to think what the phenotype of the knock-outs. When you're knocking out the wild type TTR gene, what happens? Do you know that? Is that part of--?

Let me have Akshay address that.

There is a model of TTR amaloydosis, 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 knock-out, Akshay, you should comment on that.

The knock-out mouse was published some time ago and it's essentially phenotype-less, Simos. So that has been amongst the many other reasons, our ability to target both wild type and mutant, etc. This was one of the attractions to this target that even people are entirely deficient in this would not be expected to have any significant phenotype.

Okay. Thanks.

Quick question on the RSV front. Do you--can give us an update on the enrollment? And if not, maybe a projection about the completion of enrollment or when we can expect to see data?

So let me answer that and then maybe Akshay can add in.

I think it's too soon to give you any completion date timing. As you know, the study just got started up in early March, late February. And it's actively accruing sites. We have multiple patients, many patients in the 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 that's gone into it, we find 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?

No. I think you've captured it, John.

Excellent. Thank you.

Thank you.

(Operator Instructions)

And our next question comes from the line of Stephen Willey with Thomas Weisel. Please proceed.

Hi, good afternoon. Thanks for taking my questions.

Hey, Stephen.

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 kind of where you guys start with dosing, where you end up, and maybe just the number of patients that we're going to see in each cohort?

Right.

We haven't yet but that will be presented relatively soon at ASCO. Obviously there's an abstract that you'll see before ASCO, as you know, but we'll update with more data at the actual presentation for ASCO. And so--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. So--but we are now in multiple dose cohorts with double-digit numbers of patients in the study.

Okay.

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

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

All of that will be made available when the poster is presented. Bear in mind, this is just the initial experience and the initial dose cohorts of the study. People should gauge their expectations accordingly.

And then I believe, Barry, you mentioned some--the 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 yield improvements and not necessarily manipulating a cell line so that you're getting different glycosylation patterns?

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

All right. Thanks.

Thanks, Steve.

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

Thanks, Ann. Thanks, everyone.

Again, as you can tell we're really excited about all the advances we 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.