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Operator
Good day.
My name is [Skinner], and I will be your conference operator for today's call.
At this time, I'd like to welcome everyone to Ligand's Fourth Quarter 2017 Earnings Release Conference Call.
(Operator Instructions)
I now turn things over to Todd Pettingill, Director of Corporate Development and Investor Relations.
Todd Pettingill
Welcome to Ligand's Fourth Quarter of 2017 Financial Results and Business Update Conference Call.
Speaking today for Ligand are John Higgins, CEO; Matt Foehr, COO; and Matt Korenberg, CFO.
As a reminder, today's call will contain forward-looking statements within the meaning of federal securities laws.
These may include, but are not limited to, statements regarding intent, belief or current expectations of the company and its management regarding its internal and partner programs.
These statements involve risks and uncertainties, and actual events or results may differ materially from the projections described in today's press release in this conference call.
Additional information concerning risk factors and other matters concerning Ligand can be found in Ligand's earnings press release and public periodic filings with the Securities and Exchange Commission, which are available at www.sec.gov.
The information in this conference call relates to projections or other forward-looking statements represents the company's best judgment based on information available today and reviewed by the company as of today February 21, 2018, do not necessarily represent the views of any other party.
Ligand undertakes no obligation to revise or update any statements to reflect events or circumstances after the date of this conference call.
At the time, I'll turn the call over to John Higgins.
John L. Higgins - CEO and Executive Director
Thank you.
Welcome.
I will start things off by providing some brief comments as a year-end review and then I'll add some perspectives for the opportunities we see in 2018 and beyond.
First, 2017.
This past year, we delivered on all fronts.
Financially, it was a very strong year.
At the start of the year, our outlook was for $130 million in revenue with some upside potential for contract payments.
The year finished with revenue of just over $141 million, driven by higher royalties and higher contract payments.
The cash flow from operations also exceeded our expectations.
We entered into 10 new license agreement during 2017 and have over 95 partners and more than 165 shots-on-goal or fully funded programs.
Our lead royalty-bearing assets are performing very well, and our portfolio model is driving with high-quality programs successfully advancing in the clinic and new programs being added to the portfolio at a good pace.
Of note, one important product, EVOMELA, had its first full year of sales, a second product, Baxdela, secured FDA approval and recently launched and a third drug candidate SAGE's brexanolone completed successful Phase III trials for PPD.
Now we reported positive results for our GRA diabetes product in the second half of 2017.
This is the leading drug candidate for a novel and potentially major category in the diabetes space.
It has shown highly impressive efficacy in type 2 diabetes and has a potential as a treatment for type 1 diabetes as well.
We are in discussions with companies for potential licenses for both worldwide and regional rights.
While there is interest and demand by companies to license the drug, this is Ligand's largest unpartnered program at this time.
So we will be patient to secure the deal that optimizes the potential for our stakeholders.
Also in 2017, consistent with our business model of acquiring and leveraging drug technologies, we closed an important acquisition of Crystal Biosciences, expanding our OmniAb technology platform to include another species of animal.
As we look forward, we expect 2018 to be the year when 2 drugs in which Ligand has economic rights, each will generate more than $1 billion in annual revenue.
First, Promacta just came off a very large fourth quarter, and Novartis is managing the drug superbly.
Q4 sales were $255 million, that is up 43% or $77 million over Q4 2016.
The drug has been on the market for over 9 years.
So to see that level of growth now is particularly impressive.
In 2018, Promacta will become a $1 billion molecule, with analysts projecting continued strong growth beyond.
We are very pleased with our drug discovery contribution for that drug back in the 1990s and are proud to note the substantial medical benefit it offers patients.
And for Kyprolis, given recently reported sales numbers, that drug appears to us to also be on track to exceed $1 billion in worldwide sales in 2018.
As investors who follow us know, Kyprolis is an Amgen drug that uses Captisol in its formulation.
We have a license agreement with Amgen, but it's not involved in the commercialization or development of the drug.
Amgen reported $227 million in Q4 Kyprolis sales and Ono reported $16 million for total Q4 sales of $243 million.
Now Kyprolis is a drug that likely would not be possible as a human treatment, if not for our technology Captisol.
Our technology enabled that drug back in the days when carfilzomib, the active ingredient, was still under development by, then small privately owned, Proteolix.
Now it's a worldwide drug and an important treatment option for patients with multiple myeloma.
Once again, we are proud of our contributions to provide innovative technologies that make drugs possible.
And as I mentioned, Melinta's drug Baxdela recently launched and will begin booking royalties on that product in 2018.
This year, we expect SAGE to file its NDA for brexanolone in PPD.
And we expect Retrophin to initiate its Phase III trial with Sparsentan.
Our OmniAb antibody discovery platform is doing very well.
The OmniAb technology is highly valuable and is one part of Ligand's business where some investors may not fully appreciate its value and potential.
Our financial and licensing success with OmniAb, factors driven by insiders in the industry are underscoring the significance of the technology platform.
Two years ago, in January 2016, when we acquired OmniAb, we projected at least $18 million of revenue from the OmniAb business over the following 2 years.
We actually booked over $33 million in OmniAb revenue in that time period, nearly double our original outlook.
In addition to strong financial performance, we are signing up new partners at a faster rate than expected.
And by the end of this year, we expect 10 OmniAb antibodies to be in human trials, also more than our outlook just a year ago.
The industry's need for drug discovery technology for antibodies is so significant that we expanded our investment into the platform by acquiring Crystal Biosciences to add their technology to our growing platform.
2018 will generate more advancements for the OmniAb platform.
And we are excited with what we see in the pipeline for prospective deals and partner news.
In 2018, we are now developing a promising new product we acquired last month, CE-iohexol for diagnostic imaging.
This is a very large existing market and the product candidate we are developing could be a significant improvement over current offerings.
Finally, factors outside our control are also substantially benefiting Ligand.
The new tax law has meaningfully increased our long-term outlook for cash flow and profitability as our projected tax rate has been reduced by more than 1/3.
And in terms of our portfolio performance, just last month there was a major study conducted by MIT that shows the success rates of drug programs advancing to approval have increased.
We believe this can be attributed to many factors, including better decisions with advancing programs and a more favorable regulatory environment.
This is very meaningful for Ligand, as we have over 165 programs at all stages of development.
The newly published success rates would imply that a higher number of our partner programs have the potential to advance to approval.
With that, I'll now turn the call over to Matt Foehr to talk more about our portfolio.
Matthew W. Foehr - President and COO
Thanks, John.
I will start off with a review of a few recent developments for select partner programs and general progress of some of our partners at a corporate and financial level.
I'll then touch on recent licensing activities and the status of our technology platforms.
And I will review the status of our integration of the Crystal Bioscience business following our acquisition in October.
Starting with partner programs, in the fourth quarter, SAGE Therapeutics announced that brexanolone achieved the primary endpoints in 2 Phase III trials in postpartum depression or PPD.
They reported statistically significant mean reductions in the Hamilton rating scale for depression or HAMD score compared to placebo at 60 hours in both of the placebo-controlled multi-center trials.
And they reported that brexanolone provided a rapid and durable reduction over 30 days in depressive symptoms, as measured by HAMD.
As a bit of background, PPD is a common biological complication of childbirth affecting a subset of woman typically commencing in the third trimester of pregnancy or within 4 weeks after giving birth.
It's estimated that PPD affects approximately 10% to 20% of women giving birth in the U.S. And up to half of these cases may go undiagnosed without screening.
There are no approved therapies for PPD, and there is clearly unmet medical need for treatment.
We continue to be very impressed with the work that the team at SAGE is doing and look forward to their previously reported plans for an NDA submission this year.
Also in November, our partners at Viking Therapeutics announced positive top line results from a Phase II trial VK5211 in patients recovering from hip fracture.
The study met its primary endpoint, demonstrating statistically significant dose-dependent increases in lean body mass, ranging from 4.8% to 9.1%, following 12 weeks of treatment.
Viking also reported that statistically significant improvements were also reached on a number of key secondary efficacy endpoints as well.
We were encouraged by VK5211's preliminary safety and tolerability profile and particularly that no drug-related SAEs were observed.
This is particularly impressive, given the medical fragile -- the medically fragile profile of hip fracture patients, many of whom are older adults with multiple comorbidities.
As it has been in historical background, VK5211 is a novel orally available nonsteroidal selective androgen receptor modulator, or SARM, that was designed to selectively stimulate muscle and bone formation with reduced activity in peripheral tissues.
The drug was originally discovered by scientists here at Ligand and our team completed the early clinical work for the program.
So it's especially exciting for us to see such strong clinical data in hip fracture setting where the medical need is so substantial.
Our partners at both ARMO BioSciences and Viking Therapeutics following their clinical data, both recently completed major financings.
ARMO in the form of an IPO with gross proceeds of $147 million and Viking having raised over $70 million in a follow-on offerings in support -- to support further clinical work of Ligand partner programs.
Turning now to our OmniAb technology platform.
Antibody research is one of the largest areas of R&D investment by pharma and biotech, given the potential medical impact for major new medicines and importantly, that the published clinical and regulatory success rates for antibodies are generally better than those for small molecules.
And we're continuing to see substantial progress from our antibody-focused partners.
In Q4, we received a $6 million milestone payment from HanAll Biopharma, in relation to their OmniAb-derived novel anti-FcRn antibody in clinical development for autoimmune diseases.
There are now 5 OmniAb-derived antibodies in the clinic.
And we expect that number to increase in as more partners are starting up shortly.
We continue to receive reports from partners who are expanding their use of the OmniAb platform.
As a quick example, one global biotech partner recently let us know that they started campaigns to evaluate 16 novel targets with OmniAb rodents at the start of 2018.
Additionally, as announced, we've recently added new OmniAb platform deals with Glenmark and Ferring Pharmaceuticals and expect that we will add other new OmniAb partners this year.
Integration of the Crystal Bioscience's business and the OmniChicken into our OmniAb platform has gone extremely well.
The team in Emeryville, which we now refer to as Ligand north, is highly motivated and productive, and they're well positioned as we continue to add-on new partnerships and expand existing ones.
We've received multiple success-related milestones for the OmniAb programs in Q4 and expect others to occur this year.
We've now successfully expanded some previously existing OmniAb relationships to include access to OmniChicken, as our partners see the clear value proposition and the need for their more complex therapeutic targets.
The addition of the OmniChicken platform has been complementary to the OmniAb technology, and as we expected when we did the deal, has furthered Ligand positioned as the world leader in novel transgenic antibody discovery platforms.
Species diversification is known to be very important in the antibody discovery, due to the expended complexity of the therapeutic targets that are now being pursued by our industry and given that not all species will yield the same results.
We feel strongly that we now have the world's premier offering of fully human antibody discovery technologies based on the number of species and the variety of species and the largest number of partners broadly deploying the platform.
We're looking forward to hosting many of our OmniAb partners at a Partner Symposium at the Protein Engineering Summit or PEGS meeting in Boston, again, this year in late April.
We spent considerable effort managing our alliances and ensuring our partner success in finding the best possible therapeutic antibodies.
And meetings like PEGS are an efficient way for us to interface with many partners from around the world as they provide updates on their progress.
We also continue to enter new agreements and expand existing relationships around our Captisol technology.
And I note that in 2017, our Captisol type 4 and type 5 Drug Master Files were converted to electronic format with the FDA to help streamline I&D and NDA filings by our current and future partners.
We continued to expand the large safety database for Captisol with more studies being prepared for addition to the DMFs in 2018.
I also want to mention our liver-targeted prodrug or LTP technology briefly as well.
And point out that in April, we expect presentations for LTP-related programs at both the EASL International Liver Conference as well as the National Lipid Association Scientific Sessions meeting.
And I'll conclude now with a brief remark about some of our continuing internal R&D.
We recently announced that we've established a new program to develop Captisol-enabled next-generation contrast agents for diagnostic imaging, and we're starting with Captisol-enabled iohexol.
Like other R&D investments, our plan is to pursue studies and data sets that create partnering value inflection points.
Our focus with this program is on hospital-based diagnostic imaging products that could benefit from reduced renal toxicity, which is a major issue and is a subject of a report and editorial just last week in the New England Journal of Medicine.
This new internal R&D program leverages our Captisol technology more broadly and also leverages new intellectual property we gained via the acquisition of Verrow Pharmaceuticals, with whom we had a previous Captisol relationship.
We look forward to updating you as we make progress towards I&D submission and initial clinical development.
And with that, I'll turn the call over to Matt Korenberg to discuss the financials.
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Thanks, Matt.
2017 was a year of significant financial and operational success for Ligand.
Revenue growth of almost 30% and earnings growth of more than 50% contributed to a year in which we exceeded our guidance and continued our track record of strong annual growth with respect to revenue, royalties and cash flows.
Turning to financial results.
Total revenues for the quarter were $50.5 million and included royalty revenue of $28.3 million.
Royalty revenue grew 45% over the year ago period and total revenue was up 32%.
The royalty growth largely reflected higher Promacta and Kyprolis royalties.
Milestone in license revenues were $14.4 million in Q4 versus $9.5 million for the year-ago period, with the increase due to the timing of achieving milestones and the contribution from OMT.
In particular, I'd like to call up the HanAll sublicensing deals struck at the end of the year.
As mentioned in the press release at that time, Ligand licensed the OmniAb technology to HanAll in 2014.
OMT helped discover an antibody for HanAll.
And now a couple of years later, HanAll has out-licensed the rights to that antibody to separate parties, first in China and then in the rest of the world other than Korea where HanAll continues to develop on its own.
These out-licensing deals resulted in over $6 million of payments to Ligand so far.
And if the programs advance as expected, there will be more to come.
While not all OmniAb contracts include sublicensing sharing, this transaction is one example of the ways Ligand can capture more upside from the platform in the future.
Our Captisol material sales for the fourth quarter were $7.7 million compared to $9 million in the Q4 2016, due to timing of orders throughout the year.
Regarding gross margins, our Q4 gross margins for Captisol were slightly higher as compared to the first 9 months of the year as well as the prior year period.
As we mentioned consistently, our mix of commercial and clinical material sales can shift significantly from quarter-to-quarter and year-to-year resulting in swings in gross margin.
Our material sales cost translated to a slight improvement in overall corporate margins.
In 2017, our overall gross margin was 96% compared to 95% in 2016.
On the expense side, our Q4 R&D and G&A cash operating expenses were in line with our expectations.
And for the year, we had $30.3 million of cash expenses.
For the quarter, we reported adjusted net income of $29.6 million or $1.31 per diluted share compared to $16.1 million or $0.74 per diluted share for the same period last year.
In Q4, we generated $31.3 million in operating cash flow, an increase from $21 million of operating cash flow generated in the year ago period.
For the full year 2017, total revenue was $141.1 million versus $109 million in 2016, representing almost 30% year-over-year growth.
Revenue growth translated to significant increases in cash flow as well.
We generated $93.6 million in cash from operations in 2017, up from $63 million in 2016.
For 2017, we reported adjusted net income of $72.5 million or $3.26 per diluted share compared to $46.7 million or $2.15 per diluted share for 2016.
The outperformance on EPS relative to our most recent guidance was primarily attributable to the revenue outperformance and favorable tax benefits -- tax rate benefits relative to our assumed tax rate for guidance.
As a reminder, our adjusted EPS is reported on a fully taxed basis despite the fact we pay less than 1% cash taxes as a result of the utilization of our NOLs and other tax assets.
As mentioned in our 8-K we filed at that time the tax act was enacted, our historical tax rate of 36% to 39% we now expect will be 22% to 24%.
2017 and prior periods reflect the higher rates, while 2018 and forward will reflect the lower rates.
On the balance sheet, we finished the year with just over $200 million of cash, cash equivalents and short-term investments bolstered by the $93.6 million of operating cash flow that I mentioned.
One quick note on share repurchase.
Since our Q3 earnings release, we've repurchased over 20,000 shares at an average price of about $144 a share for an aggregate price of $3 million.
Related to our GAAP net income for 2017, as outlined in our earnings release, GAAP net income for the year was $12.6 million.
However, this figure was significantly reduced by a $32.8 million charge related to deferred tax assets as a result of the new tax act approved by Congress in late 2017.
Turning now to guidance.
As detailed in today's press release, we're introducing full year 2018 financial guidance.
We expect continued solid revenue and earnings growth for 2018.
For the year, we expect about $116 million of royalty revenue, $23 million of Captisol sales and at least $25 million of milestones and license fees.
In addition, we see upside potential of $20 million from milestones and license fees.
And as I've detailed in previous years, this milestone and license revenue will come from a variety of sources and together with $20 million of potential upside revenue milestone we span more than 70 possible events.
We foresee the estimated $25 million of milestone revenue consisting of $6 million to $7 million of annual license fees, more than $5 million of clinical trial-related milestones and $4 million or more from each of sale-based milestones, sublicensing sharing and collaboration revenue.
These revenue components all translate to full year 2018 revenues of at least $164 million, with upside from the milestone and license fees.
Adjusted earnings per diluted share, we'd expect to be at least $4.22.
One reminder about this guidance, it excludes any revenue from a potential GRA partnership as we continue to evaluate our options for the appropriate.
In terms of quarterly pacing for the year, I'd like to remind investors the impending change for our royalty revenue, recognition timing as a result of ASC 606, the new revenue standard being adopted by all public companies.
First, as a reminder, the royalties related to our partners 2017 fourth quarter sales will not be booked as revenue by Ligand.
The royalty we would have previously recorded as revenue in Q1 will result in approximately $30 million of cash flow that will not be booked as revenue in any period, but rather will be recorded as an adjustment to the operating -- to the opening balance sheet for 2018.
Thereafter, our royalty recognition will reset to coincide with our partners underlying revenue for the same quarter.
Or to put it another way, we'll no longer book royalties on a one quarter lag.
Therefore, Q1 will become our lowest quarterly royalty number each year and each subsequent quarter should increase in line with the partners underlying revenue growth and adjusted for step ups in our royalty rates as the year proceeds.
As a result of this accounting and based on our current estimates, we'd expect about 15% to 20% of the year's revenue and earnings to be recorded in Q1, followed by about 25% in each of Q2 and Q3, with Q4 being the largest quarter at about 30% to 35% of the year.
We'll also update investors on these trends throughout the year, if we see any significant deviations.
Lastly, just a reminder that our adjusted diluted EPS guidance excludes stock-based compensation expense, noncash debt-related costs, changes in contingent liabilities, transaction-related amortization, Promacta's net losses of Viking Therapeutics as well as the fair value adjustments to our holdings and their common stock, convertible note and warrants, mark-to-market adjustments for amounts owed to licensors, changes in contingent liabilities related to our CBRs, the excess convert shares covered by book -- the bond hedge and certain other onetime nonrecurring items.
With that, I'll turn the call back over to the operator, and open up for questions.
Operator
(Operator Instructions) And our first question today comes from Joe Pantginis from H.C. Wainwright.
Joseph Pantginis - MD & Senior Healthcare Analyst
Want to focus a little bit or more than a little bit on OmniAb platform, specifically the BD process involved in signing new partners and with the ultimate goal of getting to your capacity to continue to deliver the kinds of deals that you've been doing.
Is it more of a sense of tech transfer and what -- any potential personal needs you need internally?
Matthew W. Foehr - President and COO
Thanks, Joe.
This is Matt Foehr.
Obviously, we -- the selling proposition for OmniAb is a very strong one.
We're the only antibody discovery platform with 3 species.
We are the platform with the most partners.
We've got strong market protection with patents and clear freedom to operate.
And now multiple partners in the clinic and also some pretty high profile partners in the clinic, which means a lot from a technical perspective.
As I said in my remarks, we expect we will do more partnerships we've done till this year.
We expect to do more.
The addition of the chicken as well is a real important complement to the platform.
Our existing partners have -- understand the value that the chicken brings from a biogenetic distance perspective and what that means in terms of being able to discover antibodies that are probably more difficult to find in rodents.
And so we've been successful in signing up new partners or expanding existing relationships and also signing up new partners who are interested in both the rodents and the chicken.
So I think the selling proposition is very strong.
The beauty of it is that the partners are the ones doing the work downstream.
So from a capacity perspective, we feel very well positioned to be able to sign up new partners and send them on their way.
The other piece is we're seeing broader use of the platform as well.
I referenced in prepared remarks one of our global partners who recently shared that they kicked off campaigns for 16 novel targets at the beginning of the year, and we're seeing similar things with other partners as they expand the use of the platform.
Joseph Pantginis - MD & Senior Healthcare Analyst
Very helpful, Matt.
And question for Matt Korenberg, if you don’t mind.
I know we're a little ways away, little about 1.5 years or so, but just -- maybe if you could remind us at least what some of your current plans might be revolving your existing convertible?
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Sure.
Thanks, Joe.
As folks probably are aware, we have $245 million convertible note outstanding that comes due in August of 2019.
As folks are also well aware, we are significantly cash flow positive and have a couple of hundred millions of dollars on balance sheet today.
So unlike many biotechs who sort of view that as permanent piece of the capital structure, we view that as opportunistic get the time, and we'll continue to think about our capital structure in a opportunistic way.
If we do not do any significant M&A between now and the maturity of the convert, we should have more than enough cash to repay the underlying principle off the balance sheet and any in the money portion that's not offset by the bond hedge, we could satisfy in either shares or cash at that time.
To the extent we find significant M&A to do between now and then, we'll obviously consider how to finance the company at that time, but I'd expect that we'll figure that out as we go.
Operator
Our next question comes from Drew Jones from Stephens Inc.
James Paul Rutherford - Research Associate
This is James Rutherford on for Drew.
I want to start by digging in on to the 2018 guidance a little bit.
Specifically, could you provide more detail and your expectations for Promacta and Kyprolis?
It sounds like it's safe to assume over $1 billion revenue for each, but maybe more specifically what you're expecting on those 2 products?
John L. Higgins - CEO and Executive Director
Sure.
So as folks know, we typically look to third-party research analysts for the covering partner companies.
So folks that cover Novartis and Amgen and what they say about the potential for Amgen for Kyprolis and Promacta, respectively.
When we look at those numbers today, some are updated, some are not.
But we see about $1 billion to $1.050 billion in those numbers on -- in -- at a average or consensus for the folks that are out there for Promacta and Kyprolis.
And so that's basically the number that we've got underlying the guidance there.
James Paul Rutherford - Research Associate
Okay.
Helpful.
Just to kind of restart the year out.
And then second question, I'll hop back in the queue is, can you give any more color on your GRA partner effort?
Should we interpret that patients in that search process as an indication that the process might be on time limit that was a little bit different than the one that originally laid out?
Or how should we think about that commentary around patients there?
John L. Higgins - CEO and Executive Director
Yes.
Well, thank you for the question.
This is John.
We don't know the expectation is by investors for timing to close the deal, but we wanted to give an update.
As we say, we don't give guidance for time lines or specifics for deal expectations.
But we simply wanted to comment, since the data came out last September, that we are in active discussions.
There is a genuine interest for worldwide deals as well as regional deals for major markets around the world.
And putting deals together is partly a matter of soliciting interest, but also trying to figure out what the best development path and timelines are.
So there are a number of elements that go in any general licensing effort.
But we wanted to comment on it.
We're very pleased with the program, the market is large, and we're excited about the data.
And our given guidance for a deal timing, but wanted to reinsure our investors that it is getting our full attention, and we will do our best to put it together the best deal and path forward possible.
Operator
And our next question comes from Matt Hewitt from Craig-Hallum Capital.
Matthew Gregory Hewitt - Senior Research Analyst
I guess, you provided a nice update on a couple of the -- I guess, the Big 6 and one of the Next 12.
I'm just curious if there was -- if there is anything in either of those other 2 buckets from your pyramid that we should be, I guess, paying attention to a little bit closer as we look into 2018?
Matthew W. Foehr - President and COO
Yes.
This is Matt Foehr.
Thanks, Matt, for the question.
Just a couple I'll point out.
In the Next 12, Viking program VK2809, which is what we've called historically, TR Beta, that's another program with Ligand heritage that's expected to see data this year on hypercholesterolemia or NASH.
That's a program that I think folks are starting to pay a lot more attention to justifiably given the markets that it can address.
Viking is also pursuing a couple of orphan indications for that as well, X-ALD as well as GSD Ia.
So we expect to see some clinical trial starts and data for that program.
I'll also point to the JNJ-64007957 that's an OmniAb program, we expect -- an anti-BCMA, we expect to see based on ClinicalTrials.gov disclosures data potentially later this year.
Other OmniAb program, the Activo programs and other one that looks interesting and exciting.
And then another partnership that's -- the Captisol one that is also more in the antibody space, although it's a Captisol partnerships through the AMG 330 with Amgen.
We were proud to expand the relations with Amgen last year enter into a new deal for Captisol for their AMG 330 BiTE program that's in development for cancer.
So those are ones I'd probably kind of initially point to of top the head.
Matthew Gregory Hewitt - Senior Research Analyst
That's great.
And then maybe one additional one on a more current opportunity, the EVOMELA.
How should we be thinking about that ramp?
I mean, the way that you typically think about your guidance Promacta and Kyprolis using street estimates, are you going to use a similar type strategy for that drug and maybe what were you thinking for '18?
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Yes.
It's Matt Korenberg here.
So with EVOMELA the coverage for Spectrum is less robust, and those that do cover don't break out the products as many -- high -- it's a higher percentage don't break out the product as for the other companies.
So it is a little bit tougher.
Last year, when the product had just launched, we basically took Q4 and annualized the number and that was what we used for our guidance last year.
This year, it's a little bit more of a hybrid between the 2 of looking at the most recent quarter and then the covering analysts.
We, right now, haven't really commented on the specific number, but at Analyst Day back in November, the most recent quarter at that time was about $10 million.
And I think we showed at that time $30 million to $40 million range.
We still expect it to be somewhere in the middle of that range.
But we'll wait until we see the Q4 number from Spectrum and then the updated research analyst and we'll head -- narrow in on a more specific number for that.
Operator
And our next question comes from Larry Solow from CJS Securities.
Lawrence Scott Solow - MD
Just one housekeeping question.
Just on the going forward, I guess, logistics behind reporting, like, we have to wait now until your partners report, I guess, for you can provide your numbers, is that how is that's going to be?
John L. Higgins - CEO and Executive Director
Yes.
Thanks, Larry.
Yes, as a matter of course, we will try and report towards the end of our window to capture as many of the partners reporting ahead of us as possible.
As evidenced in this quarter, obviously, Spectrum is reporting after us this quarter.
It may happen that they're elsewhere, one or more partners would report after us.
We'll still be required to estimate what we think the revenue was in that quarter and what we'll endeavor to do is, is do our best to do that on our own and with the help of our partners behind the scenes on confidential numbers.
Lawrence Scott Solow - MD
Right.
And then, I guess, you could just true up at each quarter or at the end of the year or something, right, it's...
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Yes.
That's exactly, right.
Each quarter we'll have a rolling true up where we true up to actual from the previous quarter.
And if we're accurate at estimating the number, the true up should become about the same each quarter rolling forward and, therefore, we'll kind of always have the right number or closer to the right number in each quarter.
Lawrence Scott Solow - MD
Got it.
Okay.
And then just on the guidance, looks like for royalties, you have a growing little like just 30% or slightly above that.
I think in November you spoke of like a 15% to 25%, that was a preliminary growth number.
Obviously, Promacta is your biggest driver behind royalties and it's hitting the cover off the ball is that the -- so there are other drivers to that sort of increased from the preliminary to what you're -- to your revised -- or not your revised guidance, but sort of your formal guidance, if you will?
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Yes.
Very good question.
Folks will remember that at Analyst Day in November, we did some math for folks on the consensus numbers at that time were the high low numbers at that time for each of the main products.
And there was a wide range that was well below $100 million of revenue up to about $120-plus million of revenue.
And at that time, we said it could be anywhere in this range, obviously, but we expect that it will be $100 million to $110 million range, which was the 15% to 25% growth numbers that we talked about.
Obviously, with Promacta coming in with a very nice Q4 and same for Kyprolis, those numbers have come up and with $116 million revenue we're ahead of even where we thought and towards the high end of what were the highest expectations back in November.
Lawrence Scott Solow - MD
Okay.
Give us a little more color on the Captisol and the contrast agent market.
It sounds like it's 3 -- you're going to invest $2 million a year for 3 years, and then, I guess, at that point you'll -- that's sort of your guesstimate on when you'll be able to then have a better idea of what you can do in terms of the out-licensing?
And is this sort of, I guess, will this be a shorter or lower hurdle for approvals being that it's diagnostic or it's going -- still going inside the body?
Matthew W. Foehr - President and COO
Yes.
This is Matt Foehr.
We're excited about the Captisol-enabled imaging programs.
Obviously, we are starting with iohexol.
It's one of the largest in the imaging market and one of the big issues with imaging is risk of renal damage.
And as I said, iohexol, it's a product global sales or over $0.5 billion.
And there is a real opportunity there to create an improved product that has reduced incidence for potential nephrotoxicity.
So this is something we'll -- as you described, we're going to investing in a targeted way as we've done in the past, picking programs where we think answering some key questions, progressing down initial regulatory path and clinical path can create partner value driving inflection events for partnering.
And that's what we're starting off now.
So team here is really excited about it.
We're progressing.
It's kind of a new opportunity for Captisol, both from getting into this device kind of more diagnostic imaging space, I will say, and also leveraging Captisol in new ways.
So we are excited about it.
Lawrence Scott Solow - MD
It seems like a different indication, and it sounds like -- it seems, obviously, it's a big market.
So just quickly on the HanAll Biopharma, the license payment.
Was that something that was, obviously, a positive thing.
Was that ever in your -- potentially your future royalty or license fees that was pulled forward or was that sort of, I'm sure, it wasn't completely out of left field, but just trying to get a better grasp of that.
Just show us, obviously, the power of the OmniAb platform in generating revenue before -- long before anything is commercialized.
We're just trying to get a better view of that.
And then about $20 million of potential, obviously, you can't give us an exact, but I assume there's sort of a bucket where some are highly likely or maybe there is a portion that's highly likely and then there is some that's very much on the less likely side.
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Yes.
So, first on HanAll, much like with our own products and programs, we don't budget for M&A or licensing deals or sublicensing deals.
But we obviously, we are well aware of HanAll and the program, and it was advancing internally at HanAll.
So the milestones generally in the plans for it to proceed internally.
When they out-license the program, it shifts to a different milestone and mechanism scheme.
And that's really what happened there.
So it was a nice positive event, but all along we actually had in the budget that HanAll would go into the clinic last year and they end up doing that in Australia and not surprising that was a value-creating event or event that attracted a partner.
On our $20 million of potential upside milestones, obviously folks will remember that last year we outlined sort of the same dynamic.
We outlined potential of $30 million of upside last year.
We ended up achieving about 1 out of 3 of those dollars and that's really sort of as good an estimate as any.
We don't know if it'll be a little less or more this year, but these are all kind of (inaudible).
Operator
And our next question comes from Esther Rajavelu from Deutsche Bank.
Esther P. Rajavelu - Research Analyst
Can you maybe give us a flavor for how your OmniAb partnership terms have evolved since the early days.
It sounds like there is a lot of interest.
And I'm curious to know if the upfront and milestone terms has evolved with the high levels of interest?
John L. Higgins - CEO and Executive Director
Yes.
So I think, I'll say commensurate with the fact that we feel like we've got and now with multiple species we have the most partners, there is more discussion of OmniAb at antibody meetings, there was Big Antibody Meeting here in San Diego late last year, OmniAb was very prominent there.
So that's allowing us to, I will say, increase -- people understand the increased value proposition and that allows us to command better terms, in general.
So we feel very good about the terms we're getting.
We find it really interesting.
We've got a lot of the global established players, but also a number of new players, venture-funded players who are well-funded and have very interesting biology in terms of what they're going after, who are interested in pursuing OmniAb.
So we feel very good about the deals we're working on as well as the partners we have.
John L. Higgins - CEO and Executive Director
This is John.
I will add a little bit more color.
The -- what a company can charge as a function of value delivered.
And generally, obviously, Ligand, higher profile company, a public platform, much bigger team to offer service.
So for those reasons alone, we can really operate at a higher scale than what the private predecessor company OMT was doing.
But beyond that, we are offering more species, convenience in terms of working with one company.
We're continuing to improve the species types.
We're advancing our IP.
So there's a number of factors that are driving partners to us.
Ultimately though, if I can use the expression landgrab, the antibody area, it is the hottest area of medical research.
Big pharma, big biotech, small, private start-ups, they are eager to either be first or fast in securing antibodies or they are, I would say, a little bit more desperate to find any technology to help them solve very, very difficult targets.
In both examples, Ligand's OmniAb platform is truly a best-in-class alternative.
There are a lot of platforms available for licensing, but we are offering it, we're adding value and are able to get better terms, principally in the royalties, looking at tiered royalties moving those rates up a bit.
If I will comment, I will say, not only are we entering more licensing deals, we are absolutely ahead of our plan there.
Existing customers and again, this is the insider information, the industry insiders, our partners, that we're working with, they don't want publicity around a lot of these undisclosed targets.
But we have information that is showing these companies are employing our technology at a much higher level than we expected early on.
And thirdly, we are seeing existed partners are exercising options for opting in to access more of this platform.
So it is -- it's an acquisition we are proud of.
With any acquisition you place a bet, you don't know how it's going to work out.
We can plainly say 2 years since the deal, this is a profoundly successful acquisition.
And in many ways, we really do believe it is securing our future, given the quality of our science and partnerships that it is producing.
Esther P. Rajavelu - Research Analyst
Great.
That was helpful.
And then the DX imaging program, up to what stage are you planning to develop it before you seek partners?
John L. Higgins - CEO and Executive Director
Yes.
Esther, the key things, as I said, just speaking generally as we want to enter, we want to answer kind of key questions and generally, the path that we expect to follow would be an I&D path where we'd open an I&D, answer some preclinical and probably initial clinical questions, early-stage clinical questions and then leverage that data into a partnering event.
So that's generally how we're thinking about it.
Esther P. Rajavelu - Research Analyst
Okay.
And then lastly, on the $20 million potential upside for -- to the guidance on licensing revenues.
What are some of the key events that we should be looking at for -- to predict that upside?
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Thanks, Esther.
Much like the buckets of milestones that I described in the $25 million that we've included in our guidance number.
The upside falls into similar buckets.
There's -- some of it is tied to licensing and partnering events or financing events at our partners.
Some of it is tied to clinical trial success.
So as we see more and more OmniAb and other products go into the clinic or products progress that we maybe don't -- aren't sure if they'll hit this year or next year, that sort of thing, those type of things.
And so there is a bunch of things in there.
And of the 70 events or so that make up the potential events, we think this year -- I think much like the ratio of $25 million to the total of $45 million.
The number of events splits up almost that way as well.
So there's 30-plus events that make up that $20 million or so.
John L. Higgins - CEO and Executive Director
I think for investors and analysts, the big picture, our guidance is $25 million.
That is our best estimate right now.
Some of the $25 million is committed regarding annual payments.
The majority though are traditional milestones but what we estimate to be highly probable milestones that will fit easily within this calendar year or with some very high certainty of achieving.
Obviously, we have a lot of undisclosed milestones in our repertoire that we don't itemize, but we want to be transparent and quantify what the potential is.
So that's this other potential $20 million.
But to be clear, we don't view that as high probability.
We aren't even calling it well, we think 1/4 or 1/3 of that will probably hit.
We simply don't know right now.
But we quantified it and partly its success-based.
And if we just need more data and others we need to see timelines.
Sometimes companies are ahead of schedule -- on or ahead of schedule, so fourth quarter payment might hit.
Often partners are 2 or 3 months or a quarter or 2 behind, in which case those payments would slip into next year.
So, again, that's just a little bit more background, it's our goal to be as transparent as possible, but not create overexpectation for events that we truly do not have visibility or control over.
Esther P. Rajavelu - Research Analyst
Got it.
And my last question.
Can you give us -- can you help us think to whether some of that $20 million upside is related to the Big 6, Next 12 or are these programs that are outside of those that are less likely?
John L. Higgins - CEO and Executive Director
Yes.
It's really spread across the whole portfolio.
There are definitely a couple of things in there that are part of sort of Next 12 and less so on the Big 6. But yes, it's really a mix of the whole portfolio.
Operator
And our last caller currently in the queue is David Solomon from Roth Capital Partners.
David Michael Solomon - Research Associate
This is David Solomon for Scott Henry.
Three questions, one on the revenue side, 2 on earnings.
First on revenue, what new products do you expect to contribute to 2018 royalty income?
And on the earnings side, with regards to the additional milestone in 2018, how should we think of each additional $1 million in milestones to earnings?
Is it still about $0.03 a share with the new tax laws or is it more?
And regarding sequential flow of EPS, can we get any color on the sequential flow throughout the year?
Matthew Korenberg - Executive VP of Finance, CFO & Principal Accounting Officer
Okay.
So let's see.
On revenue, launching this year, as Melinta announced at the end of January, is Baxdela.
So that will definitely be a new contributor to royalties this year and the more -- the most significant.
Over the last couple of years, we've had some of the smaller Selexis' SUREtechnology related assets launch each year.
And we've made that public information when its happened, but those will be smaller contributors throughout the year.
So really Baxdela is the largest launch this year.
Next year, we hope that SAGE and brexanolone will -- if they file their NDA this year and get approval and contribute significantly next year.
But this year, it's mostly Baxdela.
On earnings, in terms of translation, I think you're referring to some comments we made at Analyst Day in the past couple of times where $1 million of extra milestone revenue contributes to the earnings of a few pennies.
Yes, it will marginally tick up for the lower tax rate, but it's really just -- it's within the rounding error when you're talking about that low of contribution.
So it's still $0.02 to $0.03 of EPS added.
And then your last question -- excuse me, about quarterly pacing.
There's not really much more color we can give.
Historically, investors and management were always able to calculate the next quarter's royalty ahead of time because we reported on the 1 quarter lag.
Really, all we're doing is shifting that to real time.
So investors will announce -- our partner companies will announce and then we'll get on a investor call like this, and we'll be sort of digesting the information real time.
We've always talked about the same quarter announcements in -- on those calls anyway.
We'll just be reporting the revenue that quarter.
So from a timing standpoint it can -- and a pacing standpoint, obviously, you can just look at 2017 strengths, as an example, and just take all the quarters and shift them back 1 quarter, and that will give you a pretty good estimate of how the pacing will work on the royalty line.
Obviously, when we're talking about overall revenue and earnings, we've got to factor in Captisol and milestones as well.
And last year, those items at the outset of the year looked like they would be spread relatively evenly quarter-to-quarter for the first 3 quarters with Q4 being larger.
That's still what it generally looks like this year, which is what contributes to that overall breakdown that I mentioned.
Joseph Pantginis - MD & Senior Healthcare Analyst
Well, thank you.
That concludes our call.
We appreciate the turn out of the questions here.
Just a quick preview, a couple of conferences are coming up.
We'll be presenting at the Roth Conference in California in mid-March and the same week, we'll also be presenting at the Barclays Conference on the East Coast.
And then later on, this spring, we will be presenting at the Craig-Hallum Conference and at the Jeffries Conference.
So hope to see some of you at those events.
Again, appreciate your time and attention and will keep you posted as our business develops.
Thank you.
Operator
This does conclude today's call.
You may now disconnect.
Thank you very much for your participation.