Mar 14, 2016
Executives
Jennifer Williams - Investor Relations Greg Demopulos - President, Chief Executive Officer Mike Jacobsen - Chief Accounting Officer, Vice President-Finance, Treasurer
Analysts
Steve Brozak - WBB Securities Liana Moussatos - Wedbush Securities Jason Colbert - Maxim Sirjay Balenger - Needham and Company Thomas Yip - FBR and Company Elmer Piros - Roth Capital Partners George Navoiko - Jones Trading
Operator
Good morning, and welcome to today's conference call for Omeros Corporation. At this time, all participants are in a listen-only mode.
After the Company's remarks, we will conduct a question and answer session. Please be advised that this call is being recorded at the Company's request and a replay will be available on the Company's website for one week from today.
I'll now turn the call over to Jennifer Williams and Omeros.
Jennifer Williams
Good morning, and thank you for joining the call today. As I'd like to remind you that some of the statements that will be made on the call today will be forward looking.
These statements are based on management's beliefs and expectations as of today only and are subject to change. All forward looking statements involve risks and uncertainties that could cause the Company's actual results to differ materially.
Please refer to the risk factors section of the Company's filings with the SEC for a discussion of these risks and uncertainties. Now, I would like to turn the call over to Dr.
Greg Demopulos, Chairman and CEO of Omeros.
Greg Demopulos
Thank you, Jennifer, and good morning, everyone. Also with me today is Mike Jacobsen, our Chief Accounting Officer.
I'll begin today's call with a corporate update, and then Mike will provide an overview of our fourth quarter financial results. We have some time reserved for questions after the financial overview.
Let's start with our ophthalmology product, Omidria. As many of you know, Omidria prevents intraoperative miosis or pupil constriction and reduces post operative pain, providing consistent and predictable management of these problems for ophthalmic surgeons and their patients.
Our primary focus has remained on expanding U.S. Omidria sales and we are pleased with our fourth quarter results.
In the fourth quarter, we achieved Omidria net sales of 6.7 million, a 105% increase over the third quarter net sales. Growth in fourth quarter sell through was correspondingly strong.
As we explained in the third quarter call, sell through represents the [univials] that the wholesalers actually shipped to ASEs and to hospitals. In addition to our net sales or sell in, sell through is a useful measure of product utilization by surgeons.
The actual number of vials of Omidria shipped to ASEs and hospitals in the fourth quarter increased 74% over that in the third quarter, slightly exceeding our growth reported in our earnings call in which our third quarter sell through was 71% greater than that of the second quarter. These fourth quarter sales reflect broad based increases over the third quarter, across all relevant parameters, average daily sales, average number of daily orders, average number of vials per order and number of new accounts.
In addition, the initial sales cycle has decreased by several weeks, with the duration between first and second sales shortening by approximately 50%. Based on the data that we are seeing, we remain optimistic that we can achieve cash flow positive sales of Omidria in the mid part of 2016.
To continue to expand Omidria sales and to broaden patient access to the drug, effective January 1, 2016 we selected and hired as employees, 26 of our representatives who were part of the inventive contracted sales force. We then hired 11 additional seasoned representatives, many with substantial ophthalmology experience, and are in the process of hiring two additional representatives, bringing our targeted sales force to 39 in number.
The newly hired representatives were fully trained and in the field by early February. We welcome our new Omeros team members, and we expect that our decision to shift to a fully in-house sales force will prove out strategically, further driving sales growth.
The conversion of our sales force has not meaningfully changed our overall cost structure, nor do we expect that it will. To expand further the reach of Omidria, in January, we entered into a commission only agreement with Precision Lens to cover territories in the Midwest not included in the territories for our in-house sales force.
These previously uncovered territories for Omidria, now blanketed by Precision Lens representatives are commonly referred to as the square states, running from Montana and Wyoming, across the Dakotas, Minnesota and Wisconsin, to Michigan and down through Nebraska, Iowa, Kansas, Missouri and Oklahoma. Precision Lens has a longstanding history of providing ophthalmic products to ASEs and hospitals in this geographical area, and has for strong relationships with the local surgeons and facilities.
Following comprehensive training on Omidria, its clinical benefits and the strength of Omidria reimbursement in its related patient assistance programs, the Precision Lens representatives began calling on potential Omidria customers in early February. Given the strong track record of Precision Lens and selling into ophthalmic practices, we expect that the Precision Lens arrangement will meaningfully add to Omidria sales, beginning no later than the second quarter of this year.
As previously mentioned, the arrangement with Precision Lens is structured solely as commission with Omeros paying only on those Omidria vials sold in the Precision Lens territory. While OMIDRIAssure, our comprehensive reimbursement service program has been fully operational for only a short time, it has clearly had a positive impact on utilization of Omidria.
As you may recall, OMIDRIAssure includes an information hotline for physicians and facilities, seeking personalized help and information on Omidria coverage and reimbursement, as well as two programs to assist patients in accessing Omidria, the equal access patient assistance program and though we pay the difference commercial reimbursement program. Enrollment in the OMIDRIAssure services has increased substantially month over month.
And the program has provided valuable information on commercial payer reimbursement for Omidria, allowing us to target and correct payment deficiencies as they arise. The distillate of all of this is that reimbursement continues to expand, with coverage for Omidria confirmed for approximately 95% of the lives ensured by the top 30 U.S.
commercial payers, as well as for beneficiaries across a wide range of regional payers. With the help of OMIDRIAssure we remain committed to our objective that every cataract surgery patient should have access to the benefits of Omidria.
Our speaker programs have also helped to expand Omidria use by addressing both its clinical benefits and economic aspects. Recognizing the importance of facility administrators and the decision process regarding use of new products, such as Omidria in their respective facilities, in addition to our programs focused on surgeons, our speaker program directed specifically to administrators is in full swing.
We have seen the reimbursement and economic concerns increasingly melt away, as evidenced by the recent article in Cataract and Refractive Surgery Today or CRST by Dr. Keith Walter of Wake Forest.
Dr. Walter, you may recall, had been a strong critic of Omidria, specifically voicing and publishing in CRST both his clinical and health care economic concerns.
After using the product and learning the facts about Omidria reimbursement and pass through, Dr. Walter has become one of Omidria's most staunch advocates.
And I have immense respect for his decision to publish in that same journal, CRST a full retraction of his earlier negative article, detailing his positive experience with Omidria, both from a clinical and reimbursement perspective. With increasing use of Omidria, the physician response to the drug has remained resoundingly positive.
This positive response is manifest through the growing number of investigator sponsored case controlled studies, some of which were reported at a high level during the European I and the Caribbean I meetings in January. The studies, conducted by cataract surgery thought leaders and patient numbers ranging from 50 to over 1,100 have examined the use of Omidria across a wide range of patients, including those with non-complex cataracts, complex cataracts, inter-operative floppy iris syndrome or IFIS and pseudo exfoliation.
The results have demonstrated statistically significant reduction in complications associated with small pupils, statistically significant reduction in usage of pupil expanding devices, statistically significant prevention of myosis during femta second laser assisted surgery, statistically significant reduction in age adjusted surgical times, and statistically significant improvement in visual acuity on the day after surgery. Detailed findings from these and other investigator sponsored studies will be presented at upcoming meetings, such as the American Society of Cataract and Refractive Surgery or ASCRS and the Association of Research in Vision and Ophthalmology or ARVO this spring.
Manuscripts are in preparation and are expected to be published in peer reviewed journals later this year, adding to the five already published peer reviewed articles about Omidria, authored by leading ophthalmologists. I will complete the overview of Omidria with a bit more good news, today, an additional U.S.
patent directed to Omidria will issue. This additional patent was granted by the U.S.
Patent and Trademark office after the patent office considered all prior art that was identified by Parr Pharmaceutical on its paragraph four notice letter concerning its abbreviated new drug application, requesting FDA approval to produce a generic version of Omidria, which could be approved no earlier than the end of January 2018, while our lawsuit against Parr is pending. We will amend our complaint for patent infringement against Parr to enforce this additional patent, along with our three other patents already included in our infringement compliant.
Obviously, we remain confident in the strength of our patents, which currently run through 2033. Turning to our pipeline, let's first focus on our MASP-2 program.
Our MASP-2 antibody OMS721 targets the elected pathway of the complement system, a key component of the immune response. Through its broad intellectual property position, Omeros controls MASP-2 antibodies and the inhibition of MASP-2 for the treatment of a broad variety of diseases and disorders.
Our current Phase 2 clinical programs are evaluating OMS721 in patients with complement related renal diseases as well as in patients with complement mediated, robotic micro angiopathies or tiamase. As many of you know, tiamase are a family of rare debilitating and life threatening disorders, characterized by excessive thrombi clots in the micro circulation of the body's organs, most commonly the kidney and brain.
The TMA family includes our targeted indications of a typical hemolytic uremic syndrome or aHUS, thrombotic thrombocytopenic purpura or TTP and hematopletic stem cell transplant related TMAs. In the second half of 2015, we reported positive data across patients suffering with each of these diseases.
You may also recall that 4R721 program, we have fast track and orphan drug designation from the FDA. This morning, we publicly disclosed the outcome of our recent discussions with the FDA, regarding our past due approval for OMS721.
Based on FDA's review of our clinical and pre-clinical data, as well as its review of our proposed plan for further development of OMS721, we are pleased to report that we have initiated a phase three program in aHUS. The OMS721 phase two program will consist of one clinical trial, a single arm, in other words, no control arm, open label trial in patients with newly diagnosed or ongoing aHUS.
The clinical package for the biologic's license application or BLA will be similar to that which formed the basis of approval for Solaris. We have also received the agreement from FDA on our ongoing manufacturing for both the phase three program and commercialization of OMS721, as well as on our non-clinical safety and toxicology plan for the drug, most of which has already been successfully completed, with no significant adverse findings.
We expect phase three enrollment in the trial to begin later this year. We also plan to pursue accelerated FDA approval for OMS721 and aHUS.
Similar to fast track, to qualify for accelerated approval, a drug must treat a serious condition and generally provide a meaningful advantage over available therapies. Accelerated approval allows a company to market a drug while it continues conducting confirmatory clinical assessment to obtain full approval.
Omeros believes that based on ongoing clinical work and well accepted data directed to the targets for OMS721, namely MASP-2, and for Solaris C5, that the conditions for accelerated approval can be met for OMS721. Our compassionate use program for OMS721 also continues to receive requests for the drug from physicians worldwide.
Most recently, OMS721 was requested for compassionate use in a patient who had an inadequate response to Solaris, continuing to display signs of active aHUS. Let's turn now to OMS824, our phosphodiesterase 10 or PDE10 inhibitor and development for the treatment of cognitive disorders, including Huntington's Disease and schizophrenia.
We are currently preparing for a redesign Phase 2 clinical trial in patients with Huntington's Disease. We have reason to believe that this design can demonstrate a beneficial effect of OMS824 in this disease.
We look forward to providing further details later this year. Our preclinical programs also have made good progress.
We remain excited about our phosphodiesterase 7 or PDE7 inhibitor OMS527 for the treatment of addiction, as well as for the treatment of movement disorders. You will recall that it was Omeros that discovered the link between PDE7 and any form of addiction or movement disorder.
Our initial focus is on addictive and compulsive disorders, and in December, Omeros was granted a U.S. patent broadly directed to the use of any PDE7 inhibitor to treat any substance addiction or any addictive or compulsive behavior.
Preclinical data indicate that PDE7 inhibitors could be a pan addition treatment, without affecting the reward system. We expect to publish later this year, the mechanism which we have elucidated for PDE7 and additions and compulsive disorders.
If the compelling preclinical data hold clinically, OMS527 could be an unprecedented advance in the treatment of addiction, which currently costs the U.S. economy approximately $0.5 trillion annually, more than cancer and diabetes combined.
With its intellectual property position, Omeros now controls the treatment of any addition or compulsive disorder with any PDE7 inhibitor. We expect to advance OMS527 into the clinic for the treatment of addiction in 2017.
We also are advancing our Plasmin inhibitor OMS616 toward the clinic. To our knowledge, OMS616 is the only human recombinant Plasmin inhibitor in development.
Depending on available resources, we plan to move OMS616 into the clinic in 2017. While the initial indication is likely to target bleeding disorders, we are evaluating recent data that indicate broader therapeutic applicability.
We look forward to keeping you informed. Our MASP-3 inhibitor program OMS906, targeting the complement system's alternative pathway, has also made significant strides.
Omeros was the first to identify MASP-3 as the activator of the alternative pathway, and through our expanding intellectual property position, we broadly control the use of MASP-3 inhibitors for the treatment of alternative pathway related diseases and disorders. Together with our MASP-2 program, we are establishing a large footprint in the complement space.
Omeros controls the inhibition of the effector or activation enzymes in both the lectin and alternative pathways of the complement system. Our current focus on the MASP-3 program is number one, optimization of our potent and functionally active antibodies against MASP-3 and preparation for scale up in advance of clinical trials, and two, identification of clinical indications that have high value, a high likelihood of clinical success and a clear pathway to rapid regulatory approval.
We are making progress on both of these fronts, and are looking forward to evaluating MASP-3 in the clinic in early 2018. Finally, we have made exciting progress as well in our G protein-coupled receptors or GCPR program.
Medicinal chemistry efforts and animal studies are continuing across several of our orphan GCPRs for which we have identified and possess functionally active compounds. These include, but are not limited to GPR17 linked to myelin formation, GPR101 linked to appetite and eating disorders, GPR151 linked to neuropathic pain and cognition, GPR161, which is associated with triple negative breast cancer, GPR183 linked to osteoporosis and to Epstein Barr virus infections and associated diseases and GPR174, which appears to be involved in the modulation of regulatory T-cells or Tregs known to be important in autoimmune disease, such as multiple sclerosis, and in cancer and organ transplantation.
We continue to strengthen our intellectual property position around these six receptors, as well as the other 48 orphan GPCRs that we believe Omeros exclusively controls. That concludes our update on Omeros' products and programs, and at this point, I'll turn the call over to Mike, for a summary of our fourth quarter financial results.
Mike?
Mike Jacobsen
Yes, thanks Greg. As Greg noted, revenue for the fourth quarter was $6.7 million, virtually all of which was from Omidria product sales.
This is an increase of $3.4 million in revenues over the third quarter. Our net loss for the fourth quarter was 19.8 million, or $0.52 per share.
This included a loss on the early extinguishment of debt of $1.3 million or about $3.5 per share, related to the prepayment of our previous loan agreement. During the quarter, we also had non-cash expenses of $2.8 million or $0.07 per share.
Now, I'd like to address some specifics regarding the third quarter versus the fourth quarter. Our reported revenue for the quarter increased 105% from the third quarter, although sales of Omidria by our wholesaler to the ASEs and hospitals or sell through increased by 74% over the third quarter.
The difference between our sell in and sell through is due to a slight build in wholesaler inventories, which traditionally occurs late in the fourth quarter, this burned through in the following -- early part of the first quarter. With regards to the pricing of Omidria, the overall price we receive per unit sold remained constant between the third and fourth quarters.
Cost and operating expenses for the fourth quarter were 24.7 million, an increase of 2.2 million from the third quarter. The increase was primarily related to incremental costs in our OMS721 research and development activities and sales and marketing costs associated with the 2015 U.S.
commercial launch of Omidria. An increase in cost of sales, due to increasing Omidria revenues also contributed to the higher costs and operating expenses.
As I mentioned earlier, during the fourth quarter, we incurred $1.3 million loss on the early extinguishment of debt, related to the prepayment of our previous loan agreement. This equates to approximately $3.5 for the fourth quarter.
Turning to the balance sheet, December 2015, we entered into a $70 million debt agreement with one of our previous lenders, Oxford Finance and a new lender, East West Bank. We borrowed $50 million at the closing of the facility, and after repaying our previously existing outstanding loan, we received 22.3 million in net proceeds.
We also have the ability to borrow through June of 2017, an additional 20 million in two tranches of $10 million each. Borrowing [indiscernible] tranches is primarily dependent on the achievement of Omidria revenue milestones.
The new loan requires interest only payments through July of 2017 and reduces the principal and interest payments that we would have paid under our previous loan, by 11.4 million, between January of this year and July of 2017. The loan agreement also contains the cash covenant, requiring that we maintain 10 million in cash.
As of December 31st, 2015, we had 28.3 million of cash, cash equivalents and short term investments available for general operations. In addition, we had a 10 million required under our loan agreement with Oxford and East West Bank on hand, which is shown as restricted cash on our yearend balance sheet.
With regards to research and development, we have stated in prior calls we would adjust our research and development spending up or down based on a variety of factors, including Omidria product revenues. We anticipate that during 2016, the majority of our research and development expenses will be related to our phase three and phase two clinical programs for OMS721, and the continuation of the technical transfer of Omidria commercial manufacturing to Hospira.
Selling, general and administrative expenses for 2016 are expected to increase slightly from the fourth quarter of 2015 run rate. As previously discussed, we expect that the cost of having in-house sales representatives will be effectively the same as that of the contract sales force.
But we will have increased costs in connection with the Precision Lens commissions and then the legal costs in defending our patents and in our pursuit of patent infringement claims related to the Par Pharmaceutical efforts to receive FDA approval for the generic version of Omidria, which should be no earlier than the end of January 2018, while our lawsuit against Par is pending. Interest expense associated with the 50 million outstanding under our credit facility will be approximately 1.4 million per quarter.
With that, I'd like to turn the call back over to Greg for Q&A. Greg?
Greg Demopulos
Thanks Mike. Operator, do we have questions?
Operator
Yes, we do. [Operator Instructions] Our first question is from Steve Brozak with WBB Securities.
Your line is open.
Steve Brozak
Good morning, gentlemen and that was a good start. Greg, you had mentioned on the sale cycle with Omidria the first and the second visits, can you give us more color as to what happens after that.
And then I've got two follow ups after that, please?
Greg Demopulos
After that meeting I want to make sure I'm following the question, Steve and good morning. When you say after that meaning?
Steve Brozak
Meaning that, when you've actually started to see the sale cycle starting to become complete, what are you seeing from the clinicians after, because you're starting to get more data back. And I know it's anecdotal at this point.
Greg Demopulos
Well, as I mentioned the sale cycle for that initial sale is coming in, meaning contracting. Also the sale cycle between the first and second sales has decreased significantly as well, by about 50%.
We're seeing -- as I think, I mentioned, the increases in number of vial sales per day -- increase in number of vials per day, increases in new accounts coming weekly. So, it's really all of the parameters we're interested in seeing and would like to see, we are seeing both, really I guess a better way to put it or a more succinct way to put it would be that we're seeing both breadth and depth in the adoption of Omidria, which is obviously pleasing to us.
What the physicians are reporting, what the surgeons are reporting, continues to be just as I think I mentioned, in the initial comments, really resoundingly positive. Those docs who use the product really genuinely see the advantages of that product pretty quickly.
There has been a focus on the pupil dilation effects, and those are very clear, I think as we ran through some of the studies that will be presented at ASCRS and also at ARVO. Now, those studies have demonstrated that there's reduced use of pupil dilating devices such as malyugin rings, there's reduction in complication rates.
There shorter surgical times. There's better visual acuity on post operative day one, and interestingly, [indiscernible] laser, which is pretty commonly used now in cataract surgery is known to be associated and it is clearly seen to cause myosis, because that laser generates a lot of energy, which brings the pupil down.
There will be a study published and presented that actually with Omidria, the drug appears to turn them to a second laser procedures really into traditional [faco] procedures, where the pupils don't come down, in fact they expand. So, those are - those are the kind of data that we're seeing.
It appears to be - you know, quite consistent. And we're pleased with that.
I don't know if that answered your question. I hope it did.
Steve Brozak
Yes, no, no, absolutely. Actually, that was the kind of color I was looking for.
I'll switch over to MASP-2, congratulations, by the way, but one of the things that I wanted to ask specifically was, when Solaris was going through its approval process, there were some patients - there are patients that have - you know, a spontaneous remission, and they obviously are included in the - in the positive data. You're saying that basically you'll have the same or the similar types of inclusion for your trial as well?
Is that - is that pretty much - you know, you're saying to us that it's a similar type of trial, is that a - is that a - is that an accurate description?
Greg Demopulos
Yes. I think that's accurate.
That's quite accurate. This - I think as you're pointing out, this will be a single study, single arm, open label.
So, there is no control. And you know, we believe that's appropriate.
We're pleased that the FDA has agreed with that. So, I think the design of the study will be obviously very similar to that of the study for Solaris.
And we're really quite pleased with the outcome of our discussions with the FDA.
Steve Brozak
Okay, and I'll end by one and jump back in the queue, on a housekeeping note, I haven't - we haven't heard much about [Zagron] and OMS103, can you give us anything on that? Or can you give us any details -
Greg Demopulos
Sure, sure. [Zagron] has not yet - has not initiated sales.
We'll be having more discussions with them, but you know, frankly, we're also looking at alternatives. That hasn't been a focus of ours - you know, clearly we're focused on Omidria.
And we're focused on what's happening with 721 in our - in our pipeline programs. But that's where we currently stand.
There have been no sales of OMS103.
Operator
Our next question is from Liana Moussatos, with Wedbush Securities. Your line is open.
Liana Moussatos
Congratulations on Omidria and all your progress as well as the pipeline. My questions have to do with the design of the phase three for OMS721 and [AHOS], how many patients are needed for phase three?
Are you going to have US and x-US sites? What other clinical data besides the pivotal trial is needed for the BOA?
And you mentioned accelerated approval, what would be the surrogated end point for that? And then for Mike, with all the cash assets that you have, the [ATN], the remaining on the secured credit facility, what's the [run way]?
Greg Demopulos
All right, let's take those. I think I'll take those in order.
I didn't write them down, Liana, but I remember - I remember them. I believe - good morning, by the way - with the design of the study, it's going to look - it's essentially the same as what Solaris needed to do.
The same or actually maybe a little better for us than what Solaris needed to do. The studies will be conducted, we expect both in - you know, the study will be conducted in both the US and Europe.
The end points will really be very similar. The population will be plasma therapy resistant and plasma therapy sensitive, AHUS patients.
Now, the primary end point, just like Solaris will be hematologic normalization. Other efficacy measures will also be considered.
With respect to accelerated approval, you know, we're assessing what the options are for that. No surrogate end point has been determined.
We don't have accelerated approval at this time. We intend, as I said, to pursue it.
We believe that 721 can qualify for that, but you know, we're going to need to have further discussions with the FDA. It was interesting that this option was actually - was actually opened to us by the FDA.
They were the ones who raised the issue or the opportunity, I should say, for accelerated approval. So, we're pleased with that.
And I think, that answers your questions about study design and where we're going.
Liana Moussatos
About of number of patients…
Greg Demopulos
The rest are sort of -- patient are going, are somewhat of a moving target, and we're still working through what we think we're going to be doing there. Of course, with accelerated approval, those numbers come down substantially and I would just look at Solaris and that should guide you pretty easily there.
With respect to cash and runway, you know our cash position. You know that we have these assets available.
It's really going to be driven, as you know, by the steepness of the slope of the uptake of Omidria. And we like the way that -- we like the progress we've made, I expect that 2016 will continue to be a healthy year for Omidria.
And we'll just see how all of that plays out.
Operator
Our next question is from Jason Colbert with Maxim. Your line is open.
Jason McCarthy
Hi guys, it's actually Jason McCarthy for Jason Colbert. Greg, can you talk about you know, the rate of inadequate Solaris therapy or even Solaris failures?
And you know, if you're - if you're thinking about pursuing accelerated approval and you can get your n equals number down, for that type of study, would you pull your patients who are patients that may have not performed as well on Solaris?
Greg Demopulos
It's a good question, Jason. And you know, certainly we're looking at all of the options around accelerated approval.
Solaris failures would be one of those of course that is going to require a definition of Solaris failure. And of course, we'll be looking at that specifically as well.
You know, as you know, I'm sure there are C5 mutations that are sort of inherently difficult to treat with a C5 inhibitor, really any C5 inhibitor that's an opportunity that's there for us and certainly one we'll be exploring. But there are others.
And I think at this point, that's about all I'm comfortable discussing, with respect to that accelerated approval path other than to say that we recognize the importance of it, I think, pretty clearly. And we certainly want to avail ourselves of that opportunity.
Jason McCarthy
Great, in terms of timing, when do you anticipate or can you give us a little bit more clarity on when you're thinking about enrolling the first patient or when you might start dosing?
Greg Demopulos
Yes, I think, we've said later this year. I would rather under promise and over deliver that so you know why don't we just -- we'll just be looking at the second half of this year, once we get everything in place to begin enrolling in the single phase three study.
Operator
Thank you. And our next question is from Sirjay Balenger with Needham and Company.
Your line is open.
Sirjay Balenger
Hi, good morning, guys. I have a couple of questions.
The first one on Omidria, I think last quarter you mentioned that at the end of the third quarter inventory levels we're pretty low, so just trying to get an idea if this 6.7 million that you reported for 4Q, is I guess the representation is true demand of the product or some replenishment of the inventory?
Greg Demopulos
No, I think it's really the former. It's true demand of the product.
Inventory at the end of Q4 was probably on the order of one week.
Sirjay Balenger
Okay and I know you kind of stayed away from giving guidance other than reaching cash flow positive status by midyear, but how should we think about OpEx and I guess more specifically R&D since there's going to be some moving parts with OMS721 and 824?
Greg Demopulos
Sure, sure. I think that OpEx is as I think Mike mentioned, we expect is going to increase over 2016 to some extent relative to Q4.
Now although, we expect obviously revenues to also meaningfully increase. So, I think, one would think about it that way.
I think the A24 study, which is specifically of mention, the study design that we're looking at and I said that we do think that there's reasonable opportunity for success there where we expect and look forward to talking more about that. That should not be too expensive, the way that we're designing and really the focus of that study.
So, we'll provide, we expect, more information as we move forward. But I think that I'd look for OpEx to increase to some extent, as we move through 2016.
Sirjay Balenger
Okay. One last one on the 721, from the ongoing Phase 2 study, do you expect to release additional data or maybe publish some of the data over the next year?
Greg Demopulos
Yes, we are looking at that. I mean I know that some folks were wondering gee, why weren't we putting data out around the Phase 2 TMA study, you know.
The obvious answer to that is we're in discussions with the FDA around the Phase 3 program. Probably not appropriate to be putting out data.
I think that the result of the Phase 3 meeting sort of speaks to that. I think that we'll look at putting out additional data from not only the Phase 2 TMA study, which is now directed to stem cell transplant related TMAs and TTP, but also as we get going on the IgA nephropathy study, as you know, we currently have a study running in renal diseases and the set of renal diseases, including C3 nephropathy, IgA nephropathy and memberno ilopathies.
So, these are underway. And as data come in, we'll release them.
Obviously we're focused on getting that Phase 3 program up, running and completed as soon as possible.
Operator
Our next question is from Thomas Yip with FBR and Company. Your line is open.
Thomas Yip
But I may within Omidria especially with the sales are really beating estimates I believe. So, related to Omidria, just wondering, going forward, because we have seen pretty impressive quarter over quarter, as you mentioned sell through by wholesalers, which is really the wholesaler shipment, do you believe that there's a more appropriate indicator of Omidria true growth versus quarter-to-quarter sales revenue?
Greg Demopulos
You know, I would look at both, but certainly the sell through is an indication of utilization right, I mean it's measuring specifically vials sold into the ASEs and to the hospitals. We're pleased with the growth and we've said, we're really not going to guide until we've got a year of - at least a year of sales under our belt.
But what we're clearly seeing is the resistance that we saw initially, as I said I think in the initial comments really melting away. The initial concern was does this work clinically?
Do we need this clinically? And I think that that has been resoundingly answered in the affirmative.
The data are all very clear, very positive, so, I think that one has largely or almost completely gone away. The other resistance has been well, G where we get reimbursed, I think that's pretty clear again, 100% of Medicare administrative contractors are reimbursing for Omidria and then you see the results that we've had with the commercial as well as Med Advantage.
Then finally, that issue, the philosophical one about G, isn’t this somehow damaging the healthcare system. I think people are now physicians and administrators are now really understanding much better what pass through is all about, that it's a budget neutral program that dollars have already been paid in.
And this is something that you learn as move through this, what the physicians understand well and how to relay information to them. But one thing that has resonated very well is that you know, this program pass through has been in place really since 2001.
And every year, dollars have been taken from everything covered by outpatient payment services -- outpatient perspective payment services so the OPPS. So, effectively, ophthalmologists, just like everybody else have been paying into the pool since 2001.
They now have the opportunity to avail themselves of those dollars and that is something that does make sense. It is again, budget neutral to the healthcare system.
Dollars are already paid in. That program's not going away, its set by [congress] People now really get that, so that's gone away in good part as well.
I'd say that's a little slower to dissipate than the other two, meaning clinical and reimbursement, but we've made substantial headway there. And I think that all of those things are going to just continue to drive sales.
Thomas Yip
Sure, I mean I think you hit on a couple of points that every [answers] of investors question about Omidria. So, I also want to find out about 721's phase three program, just want to make sure I understand it correctly.
So, it will include a single clinical trial that will provide efficacy data in AHUS, and then also, it will include safety data from ongoing phase two TMA trial, which include renal diseases as well? So, all this will be part of phase three?
Greg Demopulos
That is correct. I mean we will have efficacy data generated from AHUS patients, both plasma therapy resistant and plasma therapy sensitive AHUS patient.
The safety database however, based on our discussions in agreement with the FDA, will be drawn from really a number of indications that we run, including, as you pointed out, those where we're assessing 721 in renal diseases. So, all of those patients then feed into our safety database, which is a great outcome for us.
I mean as I said, I think we really couldn't of hoped for a much better outcome out of the meeting with the FDA.
Thomas Yip
Sure. It sounds good.
So, I guess one final follow up is so, the primary purpose, at least for now of the phase two TMA trial that's ongoing is to also provide a safety backbone. So, let's just say that, just assume that AHUS becomes improved, what will be the next step in order to expand TMA into [immunization]
Greg Demopulos
Well, remember that the phase two program, the one that's currently running as phase two, includes those patients with stem cell transplant related TMAs, also includes TTP patients. Those are potential indications as well.
Remember that some of the patients in the phase two study who were AHUS, we also expect to be able to roll into the phase three single study for AHUS. And then you've got the renal disease where there's really clear, we believe clear biological evidence of involvement of the lectin pathway, which means MASP-2.
So, that's another set of indications. There are some other things that we're looking at, Haven't spoken publicly about yet, but the lectin pathway is becoming increasingly recognized as important in a broad range of diseases.
I mean, I guess a good analogy would be TNF Alpha, in the late 80s or early 90s, that's where the lectin pathway is now. And the involvement of the lectin pathway in just a number of diseases is becoming increasingly understood and increasingly elucidated.
And I think we're in a really wonderful position there, by the fact that MASP-2 is the effector enzyme in the lectin pathway and we control the antibodies targeting MASP-2 and we control inhibitors of MASP-2 across a broad range of diseases. So, we're pretty excited about that, we're also excited about the fact that our MASP-3 program has made significant advances.
And when you look at the combination really what we control is the effector enzyme of the lectin pathway and the activator of the alternative pathway. And that's a pretty impressive piece of real estate and we think again, no guarantees on any of this, but we expect to be a major player in the complement space, and I think, what we announced this morning, puts us well on our way to getting there.
Thomas Yip
It sounds good. Thank you once again Greg and looking forward to another great quarter.
Operator
Our next question is from Elmer Piros with Roth Capital Partners. Your line is open.
Elmer Piros
Good morning, Greg. I don't think I ever seen a product cost of goods around 6%.
Is this the floor, essentially? Or do you expect that to change over time and with volume?
Greg Demopulos
Yes, I think that - I think - you know, and I want to just - I want to be a little careful in how we answer that question, Elmer, you mean you know, look there's a lot of cost that goes into developing this drug, but we expect that the cost of goods for the product will remain flat and or come down over time.
Elmer Piros
Okay. Thank you.
Mike gave a very good understanding of how SG&A's going to move in 2016, what I'd like to ask about is R&D, what would be the peak number per quarter that you would like to -- or could lend that number to? Now we are around [$15] million?
Greg Demopulos
I'm sorry, I missed the -
Elmer Piros
What would be the highest quarterly R&D number in 2016?
Greg Demopulos
The R&D number for, you know, we've not put that out. And really Elmer, it would be - even if I were going to give that kind of guidance, which I likely wouldn't, I would also say that it would be really difficult for me to do it.
It's going to depend on priorities. It's going to depend on where the revenues from Omidria are falling.
I mean obviously you know, the beauty of having multiple programs is that we can dial up and down the spend to correspond to what's coming in from the Omidria sales or from any other source of revenue that we might have, whether that be product sales, whether that be deals, however we do that. So what we're looking at clearly is how do these things balance out?
So, I really wouldn't be able to give you anything concrete with respect to R&D peak.
Elmer Piros
Okay.
Greg Demopulos
But thank you.
Elmer Piros
I tried.
Greg Demopulos
And thank you for trying.
Elmer Piros
Yes. One last -- a couple of things only left over, how many AHUS patients have you treated in the - or in the Phase II trial that could theoretically move on to the Phase III?
Greg Demopulos
Yes, we haven't - we haven't put that number out. I don't think that number's out there and we'd prefer not to at this point.
Elmer Piros
Okay. And so coming back to Omidria for the last question, is there a patient with - who has to pay out of pocket, with all the reimbursement in place and did your OMIDRIAssure program in place?
Greg Demopulos
Yes, it's a - it's a good question. That's actually what the OMIDRIAssure program is set up to do is to - is to make sure that patients can access Omidria - really all patients can access Omidria without concern for cost.
And there are two - really two different assistance programs designed for the patients. One is the equal access program that's really focused on government insured and uninsured patients.
So, obviously that would include Medicare patients as government insured. If those patients are identified in advance by enrolling them in the OMIDRIAssure program, you know, our service then comes back and identified that patient as having a supplemental or secondary insurance along with Medicare, if they do, there is no payment issue.
If they don't have secondary or supplemental, we identify them as such and then the facility or the physician has the opportunity to enroll the patient in that equal access program where they need to qualify financially, but again, those are reasonable criteria. We're not looking at W2s.
The patient needs to attest to a financial need. We simply send a vial of drug, and that drug is used on that patient.
Obviously then the facility or the physician does not bill for that vial, but it's provided as a free vial. Commercial patients, it's even easier.
That can be done after the fact. If the patient is operated on, the facility or - is not reimbursed to the full extent of the cost of the drug, we just write a check for the difference, no deductible or out of pocket to the patient at all.
So, you know, I'm sure that there are some patients who are paying a co-pay, but the program is really structured in such a way that that shouldn't have to happen.
Operator
And our next question is from George Navoiko with Jones Trading. Your line is open.
George Navoiko
I have a couple of questions, with regard to 721, everything you've done with the FDA, where do thinks stand with the ENA, European development is approximately how far behind U.S. development?
Greg Demopulos
Yes, we have plans to talk to the European regulators as well and that's in the works and we expect that we'll be updating as we move through that process.
George Navoiko
Okay, and then a couple of questions regarding Omidria. You mentioned that there are a lot of investigator sponsored trials, if you will not really trials, but case study reports with multiple patients, are you doing any phase four studies on your own in addition to what the users are doing?
Greg Demopulos
Good question, George. We are looking at those.
We have a number slated and it's just really prioritization. Those studies will likely be done obviously with a number of these sights and thought leaders who are sort of taking the initiative on their own to do these studies.
But yes, we're looking at those. You also know that we have a pediatric study currently running that when completed, would we expect provide us with an additional six months of exclusivity.
George Navoiko
Okay and what about x-U.S. with Omidria?
Greg Demopulos
We're continuing to assess the options there. Our focus has been and really remains the U.S.
launch because anything we do x-U.S. will only be benefited by the kinds of studies that are being generated, the adoption of the product in the U.S., but we see opportunities there and again we look forward to keeping all of you apprised of how we do there.
George Navoiko
Okay, so you've mentioned you're getting your third patent issued today I guess, what -- can you give a little more detail on what that patent covers and how it strengthens your case against Par?
Greg Demopulos
Yes it actually is the fourth patent. We have three that are already included in our patent infringement suit against Par.
But specifically with respect to this one is that I think as I mentioned this patent really covers all of the prior art that was cited by Par in its paragraph 4 notice letter, so, all prior art that was laid out there has then subsequently been reviewed and blessed by the patent examiner. So, that's why this patent as well as the other three, I mean I think we did our homework before every filing these patents.
We're confident in the strength of our patents. But I think that this patent addresses specifically the prior art cited by Par, all of the prior art cited by Par.
Greg Demopulos
Okay. And finally regarding OMS527 for addiction, I mean what you're saying is pretty remarkable regarding whatever the source of the addiction is whether it's drugs, alcohol, I know so in gambling, from what you're saying it seems to come down to one pathway that PDE and it seems to me that with all these different sources of addiction and different pathways involved with them that it all settles down to male or settles down to one positive history and maybe too early a question, because you mentioned you're going to be publishing on mechanism of action, but is there anything more you can say about that, I mean it seems remarkable that the impression is that, if you're addicted you take this pill and all of a sudden you're not addicted anymore that's remarkable?
Greg Demopulos
Yes, I mean, I think it actually is quite remarkable and the mechanism is really quite beautiful. As you might expect, it's tied to the VTA or the central tegmental area and the nucleus secumbants.
If you look at the preclinical data again these are animal data, but what you see is reduction in cravings or so reduction in self administration, reduction in relapse, both Q induced relapse and stress. You see extinction.
You see all of these across cocaine, nicotine, alcohol, opioids and interestingly across binge eating, I mean the binge eating paradigm with true binge eating not just appetite suppression. And you mentioned sort of this common this is there some sort of common thread.
Well, the operating theory I think I mean certainly NIDA and the leaders of NIDA believe that it's dopamine driven, right. And when you look at the mechanism of PDE7, what PDE7 inhibitors then appear to do is in the acute addiction, where patients are hyperdopaminergic, high levels of dopamine, they bring those dopamine levels back to normal, making the patient affectively udopaminergic.
In the setting of chronic addiction, where patients are - and addicts are really hypodopaminergic through the nucleus secumbants what we're seeing is what appears to be happening is an increase in dopamine levels, again returning the patient to - or the addict to a udopaminergic level. The importance of all of this too is that it's done -- it appears without affecting the reward system.
And that's really the one of the most interesting components of this, right, because all of these other anti-addiction agents decrease the craving to some extent, but it also have an effect on the reward system. So, you may decrease the craving to some extent for the drug, but you also reduce the patient's enjoyment of food, socialization, sex, sports whatever.
That makes it kind of tough, with respect to compliance. But if you can do all of the things that we're talking about without affecting the reward system, so you're really just reducing the craving, it would be, truly something quite remarkable and really unprecedented.
Those preclinical data need to hold up in the clinic to really deliver on that promise. But obviously, we're excited about the data, the consistency of the data, the reproducibility across multiple drugs of addiction, across multiple models, yes, we're very excited about it, and we think it could be a very important drug.
As we said, addiction $0.5 trillion a year, it's bigger than cancer and diabetes combined, you know.
George Navoiko
You make of the models, let's say you've done this more than just in mice and rats, regarding up-species?
Greg Demopulos
No, no, I'm talking about multiple models. These are really rodent models, which are the accepted models for these, but multiple different models, meaning you've got models for self administration.
You have models for relapse. You have models for Q induced relapse, stress induced relapse, extinction, it just -- it kind of goes on, chronic, acute.
George Navoiko
Okay. Well, that's fantastic.
Yes, can't wait to see further progress and your announcement of more or presentation of more data out of that out of that program. Thanks very much, Greg.
Good luck, going forward.
Operator
Thank you. And our last question is a follow up from Liana Moussatos with Wedbush Securities.
Your line is open.
Liana Moussatos
Thank you. Just following up on George's question about 721 in Europe, do you anticipate having to do a second pivotal trial for Europe?
Or do you think the single pivotal for the U.S. would be enough?
Greg Demopulos
We would hope that the U.S. trial -- excuse me that the single U.S.
trial would be enough. But that's going to depend on ultimately those discussions.
But that's what - that's what we - that would be our hope and expectation.
Liana Moussatos
Thank you very much.
Operator
Thank you. I'm not showing any further questions.
So, I'll now turn the call back over to Dr. Demopulos for closing remarks.
Greg Demopulos
Thank you, Bridget. That wraps up our call for today.
Thank you again, everyone for taking the time to listen in. While still early in 2016, we clearly have made significant progress across a number of our programs.
And that pace really does not appear to be slowing. We look forward to keeping you advised.
As always, we appreciate your continued interest and support. Have a good day, everyone and thank you.
Operator
Ladies and gentlemen, this does conclude the program, and you may all disconnect. Everyone, have a great day.