Memorandum

Orexigen 4Q13 – Big plans for Contrave in diabetes, prediabetes – March 12, 2014

Executive Highlights

  • Orexigen sees great potential for Contrave in obese patients with pre-diabetes.
  • The company is working towards a diabetes indication for Contrave, as well as a fixed-dose combination with a DPP-4 inhibitor; supporting studies could start later this year.

Orexigen CEO Mr. Mike Narachi led the company’s 4Q13 and full-year 2013 financial update today. The company continues to express confidence about the chances of approval for the anti-obesity medication Contrave (naltrexone/bupropion) in both the US and EU. As a reminder, Orexigen filed Contrave with the EMA in October and with the FDA in December. The drug has an FDA PDUFA date scheduled for June 10, 2014 (Orexigen does not expect an Advisory Committee), and Orexigen is in the process of responding to the EMA’s Day 120 List of Questions, which it expects to complete in the next three months. Orexigen and Takeda (Orexigen’s partner in the development and North America commercialization of the drug), are jointly preparing for a large-scale launch in the case of a US approval. Orexigen is currently in discussions with undisclosed global pharmaceutical companies regarding a partnership for the commercialization of Contrave outside of North America.  

We were thrilled to hear management talk enthusiastically and more extensively about Contrave’s potential to treat obesity in people with diabetes and prediabetes. At this year’s JP Morgan Conference, management shared that the company is pursuing a diabetes indication for Contrave, as well as a fixed-dose combination (FDC) with a DPP-4 inhibitor – given Orexigen’s partnership with Takeda we would expect the DPP-4 inhibitor to be alogliptin (Takeda’s alogliptin). Orexigen commented on these programs extensively during the presentation and Q&A today, and characterized prediabetes as a massive untapped market for anti-obesity drugs given that weight loss is one of the few proven ways to slow the progression to diabetes. Orexigen also increasingly sees the diabetes market as a key to commercial success and improved reimbursement for Contrave. Studies to support the DPP-4 FDC and diabetes indication could begin later this year, and the company does not believe a CVOT would be needed for either program due to the ongoing CVOT for Contrave, the Light Study.

On the financial side, Orexigen had $177 million in cash, cash equivalents, and marketable securities at the end of 4Q13, up from $83 million at the end of 3Q13 and $137 million at the end of 4Q12. Orexigen did not detail what drove this rise in cash.

Our top five highlights from the call are listed below.

 

Top Five Highlights

1. Orexigen commented extensively during today’s conference call on the potential for Contrave in obese patients with diabetes or prediabetes. Orexigen sees the treatment of obesity in patients with diabetes or prediabetes as a “key to unlocking the obesity market,” and as a way to further “medicalize” the treatment of obesity. Management highlighted the size of the diabetes and prediabetes patient populations with obesity (~45 million in the US). Additionally, the reimbursement for diabetes drugs (85-90%, at tier 2 or 3) is generally far better than the coverage of obesity therapies (50% and slowly rising, at tier 3). A number of large payers have reportedly indicated to Orexigen that they would cover Contrave as a diabetes drug in terms of coverage if it had a diabetes indication.

  • We were particularly excited to hear management’s extensive thoughts on the opportunities for Contrave to be used to treat obesity in people with prediabetes – we’ve been waiting for this forever! During the presentation, management cited AACE’s recent prediabetes algorithm, which lists anti-obesity therapies as an option following lifestyle modification. Given the lack of drug options for prediabetes patients, and the fact that weight loss is one of the most effective strategies to slow the progression to diabetes, Orexigen sees the prediabetic patient population as a critical potential market for Contrave. During Q&A, management noted that patients that have been recently diagnosed with prediabetes are highly motivated to lose weight (to avoid more intense diabetes drugs). Additionally, most prediabetes patients are already on-label for obesity medications. Furthermore, despite the fact that the ADA steadfastly has not characterized obesity as a disease, increasing numbers of other professional organizations are doing so – in June the AMA’s decision to do so received a lot of publicity, and in announcing its decision the AMA joined The Obesity Society, AACE, and ACC.
  • Orexigen shared more details of its pursuit of a diabetes indication for Contrave, a plan the company initially announced at the JP Morgan Healthcare Conference. Management remarked today that the additional data required could likely be obtained in just one trial, since Orexigen has already collected data on Contrave’s use in people with type 2 diabetes in the Light Study (n=900 people on a DPP-4 inhibitor) and the drug’s phase 3 program. The new trial is to test Contrave as monotherapy and as an add-on to other diabetes medications. It  will likely run for approximately six months, enroll several hundred patients per arm, and would probably cost less than $25 million. The study’s primary endpoint is to be change in A1c. Orexigen could conceivably conduct the trial itself without waiting for partner support. Management emphasized that Orexigen is uniquely primed to enter the diabetes arena, given that it already possesses long-term outcomes data, which is ordinarily a major barrier to entering the diabetes market.
  • As background: in the COR-Diabetes phase 3 study (n=505 overweight and obese patients with type 2 diabetes), patients randomized to Contrave experienced an average A1c reduction of 0.6% from a baseline of 8.0%, in addition to 5% mean weight loss. 

2. Orexigen is also pursuing a fixed-dose combination of Contrave and a DPP-4 inhibitor. According to management during Q&A, patients on Contrave and a DPP-4 inhibitor in Contrave’s phase 3 program had “very attractive” results. We imagine that Takeda’s own DPP-4 inhibitor Nesina (alogliptin) is the likely candidate for a combination product, at least in North America, since Takeda and Orexigen are already working together in this region. Orexigen noted that the potential of an FDC could be a major factor in discussions with other companies regarding partnerships for Contrave outside of North America (see below). A FDC with patent protection through 2034, according to management, would be valuable for a player looking to expand or defend a DPP-4 inhibitor franchise. From a patient perspective, management emphasized that the convenience and copay consolidation of a FDC should improve adherence and uptake. We completely agree and continue to be extremely excited about the potential here based on our conversations with patients and providers, and learnings at conferences like the 5th International Conference on Fixed Combination in the Treatment of Hypertension, Dyslipidemia, and Diabetes Mellitus (Day #1 and Days #2-3).

  • Orexigen thinks it will only need to conduct a single relatively modest bioequivalence trial before submitting the FDC (assuming, of course, that Contrave is approved). Management believes that the trial would not need to exceed 100 patients, and would only need to run for a few days or weeks (enough time to collect PK measurements). The FDC study could begin later this year.

3. In the nearer term, and in line with previous updates, Orexigen voiced confidence that Contrave will be approved in both the US and in Europe. Orexigen believes that the interim data from the Light Study will be more than enough to allay FDA and EMA concerns about Contrave’s cardiovascular safety. In Europe, the company received the EMA’s Day 120 List of Questions just a few weeks ago, and is working on responding in a timely manner. As a reminder, Orexigen indicated that the EMA's questions include manufacturing and quality, non-clinical studies, dosing regimen, and most importantly, the agent's cardiovascular safety. Orexigen hopes to receive a CHMP opinion in late 3Q14 (CHMP opinions usually precede final EMA regulatory decisions by a few months, placing a decision in 4Q14).

  • Orexigen is currently in discussions with undisclosed global pharmaceutical companies regarding a Contrave partnership outside North America. Orexigen did not disclose whether Takeda or Sanofi (Orexigen’s new manufacturing partner for Contrave) are among the interested parties. During the prepared remarks, management remarked that Orexigen is targeting global pharmaceutical companies with existing or planned large cardiometabolic franchises – a strong strategy since marketing synergies would likely exist between Contrave and cardiometabolic agents. Management also noted that the current suitors are very interested in the drug’s diabetes lifecycle opportunities as well.
  • Takeda and Orexigen’s joint preparations for Contrave’s launch in the US are well underway. Commercial-scale manufacturing of the drug began earlier this year, and Orexigen is working with new ex-North America manufacturing partner Sanofi to build additional capacity to meet expected demand outside of North America. Regarding a post-launch strategy, management noted that samples and rebates will be useful in getting patients to try the medication, but did not discuss pricing in detail (for context, Vivus and Eisai/Arena have conducted free-trial offers as well as subsequent out of pocket discounts). Orexigen also has not ruled out pilot programs with payers, especially those like Aetna (who is currently running a pilot with Vivus’ Qsymia [phentermine/topiramate] and Arena/Eisai’s Belviq [lorcaserin]) with comprehensive weight loss programs.

4. Management listed a number of areas beyond diabetes in which Contrave could differentiate itself from other anti-obesity medications:

  • Contrave’s long-term outcomes data from the Light Study differentiates it from Vivus’ Qsymia and Eisai/Arena’s Belviq, neither of which have completed a CVOT.
  • Orexigen has a relatively large amount of data on the drug’s neuropsychiatric safety from phase 3 and the Light Study, especially in patients with depression who are being treated with antidepressants. Management noted that neuropsychiatric safety is a major area of concern for many regulatory agencies, and one that agencies will not have significant reason to worry about with regards to Contrave.
  • Contrave can appeal to the female patient population interested in having children because it is not teratogenic, as is Vivus’ Qsymia.
  • Contrave is not a scheduled drug, meaning that providers can give patients samples.

5. Orexigen has filed a number of additional, currently undisclosed patents regarding Contrave that if approved would extend the product’s intellectual property protection through 2034. These patents were filed based on “unexpected, novel, and useful” findings from the Light Study. Management was tight-lipped about these patent filings during the presentation and Q&A, but we will be interested to learn more about these patents during future company updates.

Note: Following precedent from Orexigen’s JP Morgan presentation, management did not refer to its central candidate as “Contrave,” instead referring to it as NB32 (its development name) to clarify that the company is not engaged in any pre-approval branded marketing.

 

Honorable Mentions

  • Based on Orexigen’s conversations with the FDA and interim results from the Light Study Orexigen does not believe a CVOT will be required for its phase 3-ready Empatic (bupropion/zonisaminde) for obesity. Orexigen explained that Empatic contains the same dose of bupropion (the agent the FDA had a CV safety concern about) as Contrave. In line with previous guidance, management stated that it only plans to move Empatic into phase 3 with the help of a partner. Orexigen also stated its belief that Empatic could be developed in a way that could complement Contrave and that it now thinks it is best for Empatic and Contrave to have the same partner.  Orexigen did not discuss specifics on that front.

 

Questions and Answers

Q: You talked about some new patent applications. Could you provide any additional details regarding the patents for which you’ve applied?

A: We filed method patents based on insights we gained from the Light Study. We won't be disclosing any of the claims or the structure of the patents until they are published, for competitive reasons. However, for us to have confidence in a patent issuing, the insights have to be unexpected, novel, and useful. We know that these patents are novel, the results were certainly unexpected, and we’re confident that these are going to be very useful patents for us. We can probably talk more about the patents as we get closer to issuance and publication next year.

Q: Given the news that the FDA has decided that you won’t need a new CVOT for Empatic, how have your views on potential phase 3 designs changed? Should we anticipate that this news will accelerate potential partnership discussions for Empatic as well?

A: You're right that our discussions with the FDA lead us to believe that Empatic will not need an additional cardiovascular outcomes trial. For context, Empatic still contains the same dose of bupropion. Bupropion was the agent with which the FDA had a theoretical safety concern. Now that we have results from the interim analysis, we are even more confident that Empatic will not need a cardiovascular outcomes trial.

We have always thought that Empatic would be advanced in a collaboration agreement and that we would not fund additional development for Empatic on our own. One of the reasons for this is that the development of Empatic could complement that of NB32, depending on the precise positioning of the two products. Therefore, the way that NB32 is positioned would impact the process of product development for Empatic. Another reason we’d seek a collaboration agreement is that additional investment beyond phase 3 would typically be required in order to add new insights and seek new intellectual property protection to extend and broaden the patent portfolio for Empatic. Given the level and breadth of that investment, we think it is best to partner Empatic with NB32.

Q: Approval in the US would certainly be a jumpstarting milestone for NB32 lifecycle management. What else do you need to do before moving forward on some of your initiatives for the lifecycle management programs?

A: The team is already making progress there. The first steps that Preston outlined are gaining more detailed alignment with our current partner and prospective partners, protocol sketches, talking with regulators to nail down the specifics of the development path for approval of some of our lifecycle plans, and then initiation of the studies, among other things.The upfront planning phases have already begun, the dialogue has already begun, and we'll keep you posted on progress as we move forward. The next important milestone would either be us with our partners or our partners alone announcing their desire to begin those trials.

Q: Given that several of your competitors are involved in a pilot program with Aetna, how important do you think these programs are in terms of competing for the market and showing the value proposition of your drugs to payers? Will NB32 be incorporated into these types of programs if it is approved?

A: I think the pilot programs are interesting and valuable. As we understand it, Aetna has a weight-loss program as a part of its offering, perhaps as part of wellness offerings in general. We've always felt that combining a weight-loss therapeutic along with a weight-loss program is a really good way to go, especially when considering an employer-based health plan or a wellness program. I can certainly see that being an element of commercialization for NB32 as well, and we encourage these kinds of programs as one of a variety of approaches. These sorts of programs are going in the direction that we've been talking about for several years.

Q: The goal to move into the diabetes setting sounds interesting. Are you able to share anything with us in terms of the near term on Takeda's commercial preparation or the extent to which you specifically have been engaged in in that process?

A: In the near-term the medical imperative for weight loss in the diabetes and prediabetes patient populations is extraordinarily high. Our research tells us that it is much more likely that people affected by diabetes or prediabetes will actually adopt and continue using weight loss therapeutics than it is for the average overweight or obese patient who may be seeing a primary care physician for any number of reasons. It’s easier to introduce weight-loss therapeutics, and also a more likely buying opportunity for a patient or physician, if the patient is coming in to be seen for their diabetes or has recently been diagnosed with prediabetes because many have been recommended to lose weight with those diagnoses. Those insights that we've gained match perfectly with the profile for the product and also with the message that's being developed, the horsepower that Takeda can bring to that market to specifically target the kinds of physicians that are already call on and have relationships in that community.

As you can imagine, all of the finishing touches that they’re putting on now have to do with a very strong obesity launch. The sales force is being trained to target the physician audience; they’re deciding which physicians to go after specifically. They’re also putting together the message, positioning Contrave, and developing an image of what the sales day would look like, including opinion leader development, speaker program development, managed care discussions and stocking the product.

There's an extremely extensive launch plan that's been fully developed by both teams and globally reviewed by our joint steering committee, which is made up of executives from both companies. Everything is locked and loaded right down to when the reps will begin detailing the product.

Q: What's the current thinking on a panel? Can you comment on whether or not you expect to have one?

A: We're about halfway through the review process now and we have reached out proactively. To date, we have not heard that the FDA is thinking about calling an advisory committee, which isn't surprising. We believe that the data provided with the interim results very clearly address the CRL that we received.

Q: With regard to the diabetes study, is it right to assume that you would not pursue this without a partner? 

A: This is something that a commercializing partner would want to add to their life cycle plan and would want to own. However, since the cost of this one additional phase 3 trial would be pretty small, less than $25 million, I could see it as an area where we might want to go ahead and get started without a partner, depending on the timing. We’ve already started doing the work. We would approach regulators globally on the process, clarify the path, finalize protocols and get ready to go. Even if we did start it prior to consummating a rest-of-world partner, I’m sure that this could be easily adopted and funded by our existing and future partners. I wouldn’t say that partnership is a necessity before starting because we’ve already started some of the early lead time activities.

Q: Do you have any idea of how large the study in diabetes would be?

A: These are fairly typical trials. Size would be several hundred subjects per arm and the structure would likely include examining NB32 as monotherapy and then as an add-on to existing diabetes medications. Again, it's a fairly straightforward path. As an efficacy study, A1c is the primary endpoint and it's typically six months in duration.

Q: In terms of trying to think ahead, how do you go about capturing the prediabetic population commercially?

A: First of all, it's an extremely large group. The prediabetes market dwarfs the diabetes market, and there are certainly some blockbuster drugs out there for diabetes. We know that there are billions of dollars’ worth of drugs being sold in the diabetes market, but there hasn’t been too much movement in the prediabetes market other than for other comorbidities. The only thing we know of that really impacts the progression toward diabetes in the prediabetes market is weight loss.

If you think about the conversations that prediabetic patients are having with their physicians, it goes something like this: ‘Look, if you don't lose 15, 20 pounds by the next time I see you, you're well on your way to becoming a diabetic. You're prediabetic now and we're going to be putting you on a diabetes medication, most likely metformin.’ Obviously, the patient is very motivated to avoid going down that road. We think the Contrave message is going to fit into that mindset very logically. Contrave is going to help these patients lose weight and prevent that progression to diabetes in a number of patients. It makes a lot of sense. Takeda has a strong diabetes heritage because of what they were able to do with Actos and now with their launch of Nesina. They’re going to be calling largely on the same physicians with Contrave.

The recently announced AACE guidelines made it a medical imperative to try pharmacotherapy with assisted lifestyle change, pharmacotherapy alone, or surgery. We hope to get going so that we can help to curb the progression of this epidemic population towards diabetes. I think that is within reach for an obesity therapeutic. The vast majority of prediabetic patients are on-label. They are 27 kg/m2 BMI and greater with a comorbidity like hypertension, dyslipidemia, etc. A large number of prediabetes patients are on-label for an obesity therapeutic, and weight loss to a large degree.

Just to put the US market into perspective, 79 million Americans have prediabetes, and 36 million of them have a BMI of 30 kg/m2 or greater. On the diabetes side, there are about 26 million patients with type 2 diabetes and about 10 million of them have a BMI of 30 kg/m2 or greater. You 'd be hard pressed to find larger markets or more compelling need.

Q: When do you expect to respond to the 120 day questions?

A: Typically, it's about a three-month cycle and that's what is generally considered standard in terms of a clock stoppage. We believe we can certainly respond in that timeframe.

Q: Do you have any concern at all that impressive price discounting will be expected of all obesity drugs, at least initially?

A: I'm not going to comment on pricing. We haven't released pricing at this point. With Contrave, it's all about getting patients to their second and third scripts, letting them start to see the results, letting them start to lose weight and feel better. We think once that happens, we're going to enjoy good persistency, especially when Contrave is combined with a weight loss program. There are a number of ways to do that. Certainly, we look at sampling as the key tactic that will be available to us and I think potentially unique to us because we're not scheduled. I do think there's a role for coupons in this marketplace. It is definitely important to get patients to their second and third scripts, but by the same token, you don't want to be giving the drug away for a long period of time.

We’ll be giving more guidance overall financially as we proceed through the regulatory process, sometime shortly after PDUFA. We can help you understand what to expect, but obviously at launch there will be more discounting, couponing, and sampling. That will taper over time as demand, coverage, and access build.

Q: Regarding the option to co-promote NB32, how much lead time do you think you would need before you hire reps, and what kind of P&L impact might that have, both pre- and post-approval?

A: We don’t have any near-term plans to co-promote. In the past we’ve said that if there are places where we could go to augment the launch of NB32 that on its own would make sense. It could make even more sense to pair it with future product opportunities that Orexigen might undertake.

At this point, we've got all our guns focused on the milestones outlined today — the two approvals, helping with the Takeda launch as planned, the rest-of-world partnership progress, and now this exciting lifecycle plan on diabetes. There is no near-term plan, but it's always being considered and evaluated.

The only thing I would add is that with the deal that we have with Takeda, we feel that the marketplace is extremely well covered. There are some opportunities. However, there aren't any gaping holes, so we're very comfortable with the launch plan that Takeda is rolling out on NB32.

Q: As far as lifecycle management with a fixed-dose combination, can you give us some sense for how long it might take to do the PK/PD studies and submit an approval?

A: There's a variable amount of time spent on formulation. We're already done with a DPP-4, which we haven’t disclosed yet, but chemically they’re all fairly similar. We've already done the work to show compatibility and stability. Therefore, technical feasibility is completed. However, you could take either a very short amount of time to finalize the formulation to put it into clinical manufacturing, or you could take more time on the formulation. The bioequivalence studies are PK focused and just show that the fixed-dose combination has the same characteristics as the individual drugs when given in combination. We’re talking about a sample size of tens of patients, certainly not more than a hundred, and it's a fairly short duration study because you just have to administer the drug and take some PK samples.

Q: Regarding reimbursement, can you give us some sense for the difference between obesity and diabetes? If NB32 were to be approved, would a plan simply cover it if they cover everything else in the Januvia family?

A: Just to set the stage of where obesity is at right now, we've been able to see from a market intelligence standpoint that it's at about 50% plus coverage now, which is up about 10 points from a year ago. Our colleagues over at Eisai feel that they're going to be at about 70% a year from now. We’re seeing nice expansion there and my guess would be that's mainly Tier 3 coverage. With successful diabetes drug for Type 2 diabetes, they enjoy closer to 85% to 90% coverage with a solid mix of Tier 2 and Tier 3. We have conducted research with 10 major payers that cover 150 million lives and we asked them how they would treat NB32 if it had a diabetes indication. The research came back very strongly that we would cover NB32 as a diabetes drug for those patients that are diabetic and obese. You would see kind of a binary shift or an immediate shift in coverage on how NB32 would be covered with a diabetes indication. If it's combined with a drug that already has great access and coverage, our assumption is that you're going to have very, very similar coverage. These drugs are typically flat-priced.

We've taken a look at our phase 3 data sets and at the Light Study data set and the natural experiment has already been run. For example, in our phase 3 dedicated diabetes trial, we have patients who were on a DPP-4 in a placebo arm and Contrave or NB32 plus a DPP-4 in the other arm. We already know what happens to A1c, to lipids, to HDL, CRP, weight, etc. when those agents were taken separately. We've got a good view of the product profile of this and it's very attractive. In the Light Study, there are almost 900 patients that were on DPP-4s and we've collected safety and weight loss data there that's readily available.

Picture the conversation that we could have with prospective partners when we show those profiles and when we talk about how much improved the product profile and the attributes are for a current drug, whether you're playing offense or defense for those DPP-4s, trying to grow a franchise or defend one. They would also see patent applications, which I can't share with you now, for competitive reasons, but they give them this FTC patent protection potentially out to 2034. It's a very attractive strategy to focus on the patient with both obesity and diabetes with fixed-dose combinations with the new intellectual property and the safety data set that we have. It's very compelling.

I should say for the whole audience that we elected to switch from the brand name Contrave to NB32 at the beginning of this year for a couple of reasons. First, our partner Takeda made the decision to run a disease-state campaign, not a pre-approval branded campaign. Second, we thought it was prudent to use the shorthand for the generic name versus a brand name that has not yet fully been approved by the FDA or any other regulators as we approach the PDUFA. I know it's a little bit clumsy to switch, but we think that was the right thing to do up until the launch. After the launch, we’ll begin using the brand name, whether Contrave makes it through the process for the US or if it's a different name.

Q: Is it your expectation that you're going to be doing a monotherapy trial with just NB32?

A: The guidance itself knows that therapies for type 2 diabetes can be evaluated in placebo-controlled monotherapy trials, placebo-controlled add-on therapy trials and active-controlled trials. It also states that given the progressive nature of the diseases and their requirement for multiple drug therapy, the clinical drug development program should include evaluation as monotherapy and in combination. I wouldn’t necessarily say that monotherapy is an absolute requirement per se, but it’s a general expectation that eventually you will have monotherapy data. There are many reasons why it is advantageous from a commercial perspective, but a good example would be Byetta, where monotherapy approval came after the initial approval with add-on therapies.

In our monotherapy arm study, you would simply look for individual patients with type 2 diabetes who have uncontrolled diabetes, which is generally defined as A1c between about 7 % and 10.5%. Those subjects would have some form of diet, but the diet therapy as prescribed would be fairly generic within these studies. You would simply randomize those subjects into either placebo or NB-32 and that would be your monotherapy arm. Then, you would take similar patients who are already on other agents, background agents such as metformin, that's the one that's typically done first. Again, you would look for subjects who have hemoglobin A1c values in the 7 % to 10.5% range and randomize those individuals on optimized metformin to either placebo or NB-32.

Q: What would the background be as far as diet and exercise? What would you expect and hope to hit as far as statistical significance and clinical meaningfulness regarding reductions?

A: The guidance doesn't spell it out directly, but precedent says that it should be at least 0.4% or greater. We've clearly demonstrated that in our type 2 diabetes trial that was obesity focused, but in patients with type 2 diabetes, we demonstrated 0.5% placebo controlled, after you factor in the rescue medications that were taken in the placebo arm. After that analysis we saw a delta of 0.7 %. We're very confident that in a study that is designed as a primary efficacy trial using hemoglobin A1c as the primary endpoint, with patients that have a slightly elevated hemoglobin in that 7 % to 10.5% range, that we would see well in excess of 0.5% decrease in hemoglobin A1c, something that is in the range of most DPP-4s.

Q: Is Takeda not necessarily paying for this trial, and how does it work for you to potentially have a different partner rest-of-world?

A: Just a couple of months ago we got the Life Study data, and we are discussing life cycle plans and reaching agreement with our partner Takeda on what do we want to do for North America. The partnership agreement covers a 7 5%-25% cost split after that first $60 million of post approval development expenses, which are owned by us. I think the big picture depends on how Takeda wants to pursue these opportunities and on how others want to pursue those opportunities that will all get worked out. Again, a bioequivalence trial is going to be inexpensive and fast, relatively straight forward. The diabetes indication is going to be small and very low cost now that we've already harvested a quarter of a Light Study data for that $150 million total trial expense. I think it’s going to be relatively straightforward to sort out who's going to pay for which portion of all of this, depending on who wants to do what and how fast. We'll keep you posted on that. If we decide to initiate anything on our own to speed timelines, we'll let you know that too.

 

-- by Manu Venkat, Hannah Deming, and Kelly Close