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Thursday, October 1, 2015

Nuvo Research Spin-Out Should Unlock Value For Investors

On September 15, 2015, Nuvo Research, Inc. (NRI.TO) (NRIFF) announced that it plans to split into two separately traded public companies, with a goal of enhancing long-term value for Nuvo shareholders. The strategy will be to separate the pure-play commercial organization that includes a growing revenue base and significant positive EBITDA based on the strength of the Pennsaid® and Pennsaid® 2% franchise from the drug development company that is currently conducting a Phase 2 clinical trial on WF10™ for allergic rhinitis. Nuvo shareholders on record will receive shares of both companies. Nuvo management plans to distribute an information circular to investors in mid-to-late November 2015 that will go into more detail on the exact make-up of each separate company. Shareholders will vote on the matter in early 2016, with a positive vote likely leading to the transaction taking place in February 2016. What we do know is that Nuvo has a substantial cash balance - approximately CDN$51.8 million as of June 30, 2015 - and that should set up both companies with resources necessary to execute on these two distinct models.

For the purpose of this article, I will focus on what I believe to be the key growth areas for each company, which for simplicity sake I am referring to as Nuvo-Commercial and Nuvo-Development. Investors should be aware that I worked with and have spoken in-depth to Nuvo management for the preparation of this article, but that all opinions expressed on the potential future success of each company, sales forecasts, earnings potential, and likely valuations are mine alone.

Brief Background on Nuvo Research

For all intents and purposes, Nuvo Research has been operating with two distinct business units for much of 2015. In April 2015, the company provided a strategy update to investors noting its intension to spin-off WF10 for the treatment of allergic rhinitis from the company's revenue generating assets, which largely included all the intellectual property around Pennsaid and Pennsaid 2%. For the commercial organization, the strategy is to acquire new products or businesses that can become immediately accretive to profitability and cash flow. At the center of the Nuvo-Commercial will be the company's manufacturing plant in Varennes, Quebec, which is currently providing and will provide Pennsaid and Pennsaid 2% to commercial partners in the U.S., Canada, Russia, and several countries in Europe. For the drug development organization, Nuvo-Development, the key asset is WF10, currently in a Phase 2 study being conducted in Canada with top-line data expected late 2015 or early 2016.

On August 5, 2015, the company reported financial results for the first six month of 2015. Product sales for the six months ending June 30, 2015 were CDN$6.8 million, up a solid 103% from the same period in 2014. Product gross margin increased to 35% from 17% during the first six months of 2014. Much of the revenue growth at Nuvo is coming from transfer of manufactured product to its U.S. Pennsaid 2% commercial partner, Horizon Pharma USA. Yet despite the strong revenue growth during the first six months of 2015, Nuvo Research was not profitable on an EBITDA or cash flow basis. This is because the company has sizable research and development expenses associated with its active clinical programs, namely WF10. R&D expense during the first six months of the year totaled CDN$6.3 million, of which $4.8 million was associated with WF10. As a result, net loss for the six month period ending June 30, 2015 was CDN$6.3 million, or $0.57 per share based on an average of approximately 10.9 million shares outstanding.

Management feels as though the strong revenue growth and segment profitability of the commercial business is being masked by losses on the R&D side. That is probably the case, but it is important that investors understand that many small biotech and specialty pharmaceutical companies have losses on the R&D side. However, Nuvo's strategy with the commercial organization is a bit different from a typical binary event biopharma company. There are investors that like small, profitable manufacturing organizations with plenty of scale and upside based on acquiring additional commercial products. The strategy works if new products are accretive and can be added into the operational structure to create leverage. Most of these investors are not looking for binary risk. On the other hand, there are investors looking for "homeruns" in the biopharma development area and WF10 has that sort of potential; and, this potential upside is muted by operations on the manufacturing side. The impetus for the split is to separate these two distinct business lines and thus allow for maximum value creation as standalone organizations. We've all heard the saying, "One plus one equals three" when it comes to mergers and acquisitions in the healthcare industry. Nuvo is hoping the reverse is also true, and that separately these companies will have more value than the market is assigning to the combined company today.

A Look at Nuvo-Commercial

The commercial organization at Nuvo will consist of several approved and revenue-generating products, but the majority of the value for Nuvo-Commercial will come from Pennsaid® and Pennsaid® 2%. Pennsaid 2% is a non-steroidal anti-inflammatory drug (NSAID) containing 2% diclofenac sodium compared to 1.5% for original Pennsaid. It is more viscous than original Pennsaid, is supplied in a metered dose pump bottle, and has been approved in the U.S. for twice daily dosing compared to four times a day for Pennsaid for the treatment of pain of osteoarthritis (OA) of the knee.


Nuvo owns extensive intellectual property around Pennsaid and Pennsaid 2% that consists of over 30 issued and pending international patents. Nuvo-Commercial will retain the current Pennsaid 2% manufacturing and distribution agreement with Horizon Pharma plc (HZNP) for the U.S. market and the existing Pennsaid license and distribution agreements with Paladin Labs Inc. in Canada, Vianex S.A. in Greece, Italchimici S.p.A. in Italy, and Movianto UK Limited in the UK. Additionally, licensing agreements for Pennsaid 2% have been signed with Paladin Labs Inc. for Canada and NovaMedica LLC for Russia and the Community of Independent States. All future international licensing and distribution agreements for Pennsaid and Pennsaid 2% will be entered into by Nuvo-Commercial.

In June 2015, the company retained PricewaterhouseCoopers Corporate Finance Inc. (PWC) to assist it in securing international license agreements for Pennsaid 2%. Key regions available for out-licensing include South America, Central America, Africa, and Israel. The picture below shows the regions for which Pennsaid 2% is available for out-licensing and future potential sale. As investors can see, the available opportunity is significant.


Pennsaid 2% was approved by the U.S. FDA in January 2014 and is currently being sold in the U.S. by Horizon Pharma. Horizon took over promotion for Pennsaid 2% in January 2015 after Nuvo regained the rights from previous development and commercialization partner, Mallinckrodt plc (MNK), in September 2014. Horizon paid Nuvo $45 million for the U.S. rights to the drug and continues to pay Nuvo a fixed transfer price for commercial product (including any sampling that Horizon does) that Nuvo manufactures at its plant in Varennes, Quebec.

These product sales totaled CND$2.1 million in the second quarter ending June 30, 2015. For the first six months of the year, Pennsaid 2% transfer sales to Horizon Pharma totaled CND$4.3 million. Sales in the first quarter ending March 30, 2015 were larger than the second quarter due to initial inventory stocking by Horizon, which Horizon then spent most of the second quarter working down. I think going forward, the growth and trajectory of U.S. Pennsaid 2% sales at Horizon will be more accurately reflected in transfer product sales at Nuvo-Commercial.

For example, Horizon reported sales of Pennsaid 2% of $18.2 million in the first quarter 2015 and $29.4 million in the second quarter 2015. According to IMS Health, approximately 76,000 and 107,000 Pennsaid 2% prescriptions were dispensed in the three and six months ended June 30, 2015. The consensus estimate based on Thompson-Reuters for the third quarter is $33.0 million and $36.2 million for the fourth quarter 2015. For the full year, Wall Street analysts are expecting Horizon to post Pennsaid 2% sales of around $117 million in 2015. For 2016, the consensus estimate for U.S. Pennsaid 2% sales is $160 million, up 35% year-over-year. Analysts are looking for 20% growth in 2017 to $195 million and another 15% growth in 2018 to $225 million for Pennsaid 2%. I ultimately see Horizon selling enough Pennsaid 2% to surpass Voltaren Gel, a 1% topical diclofenac sodium product sold by Endo Pharma (ENDP) in the U.S. that is on pace to post around $200 million in sales in 2015 (Endo reported $96 million in sales for the first six months of the year). The impressive growth of Pennsaid® 2% in the U.S. will translate into a growing and profitable revenue stream over at Nuvo-Commercial.


Besides Pennsaid 2%, Nuvo-Commercial will continue to supply original Pennsaid to its commercial partners. Sales of Pennsaid totaled $0.6 million for the second quarter ending June 30, 2015. For the first six months of the year, Pennsaid sales totaled $2.0 million. Sales are declining due to patent expirations, the entry of generics, and transferring of marketing efforts over to Pennsaid 2%. Royalties on Pennsaid totaled $0.1 million and $0.6 million for the three and six months ending June 30, 2015. Royalties are received from Paladin Labs in Canada. Royalties are declining due to the emergence of generic diclofenac sodium in Canada. Paladin is also the Canadian commercial partner for Pennsaid 2%.

Nuvo's goal is to continue to help Horizon by providing product as the ramp gains steam throughout 2015 and on into 2016. The manufacturing mark-up has not been disclosed by Nuvo management, but investors can see the gross margin line at Nuvo has been steadily improving. The company reported a gross margin of 35% in the second quarter ending June 30, 2015, up from 32% in the second quarter 2014. I think gross margin will continue to expand at Nuvo-Commercial as Pennsaid 2% production increases. By the end of 2016, I would not be surprised to see the gross margin line eclipse 45%.

To gain approval for Pennsaid 2% outside of the U.S., management initiated a Phase 3 study of Pennsaid 2% for the treatment of acute pain in July 2015. It is important to note that the U.S. label is for pain of osteoarthritis of the knee. The Phase 3 study being conducted in Germany will evaluate the efficacy of Pennsaid 2% for the relief of pain associated with acute, localized muscle or joint injuries such as sprains, strains or sports-related injuries. This is a wider label indication than in the U.S. Top-line results from the trial are expected late 2015 or early 2016. Positive data will allow Paladin Labs to seek approval for Pennsaid 2% in Canada and position Nuvo-Commercial to sign licensing and distribution agreements for Pennsaid 2% in Europe that will likely come with upfront cash and the potential for additional milestones or royalties in the future.

I expect the majority of the current CND$51.8 million cash balance will be allocated to the spun-off Nuvo-Development, but some of the cash will remain with Nuvo-Commercial. Management believes that Nuvo-Commercial will be cash-flow positive in 2016, so the organization does not need a substantial cash balance to execute on the business model. That being said, I expect management to look to expand Nuvo-Commercial by acquiring businesses or products that can be nicely fit into the planned manufacturing and licensing strategy. This may include small contract research organizations (CROs), other topical products that can be manufactured at the company's plant in Varennes, Quebec, or commercial divisions from larger organizations that might be a better fit at a small company like Nuvo-Commercial. I also see the potential that Nuvo-Commercial looks to manufacture or distribute OTC products or generic products. The manufacturing capacity at Varennes seems more than adequate, with plenty of room to expand, and thus management's strategy to strategically expand - in whatever direction - makes excellent sense.


From an operational standpoint, I don't see Nuvo-Commercial having much overhead besides the plant in Varennes. Management has stated that Nuvo-Commercial will be profitable on an EBITDA and cash flow basis in 2016, and thus operating expenses are likely only to be in the CND$2.0-2.5 million per year range. Below I've put together a quick revenue and EBITDA ramp for investors to get a sense of what I think Nuvo-Commercial will look like in the coming years.


As investors can see, based on the projected ramp of Pennsaid 2% around the globe, Nuvo-Commercial should be quite profitable and post some impressive growth on an EBITDA basis in the coming years. From a valuation standpoint, we can now get a sense of what Nuvo-Commercial is worth. For example, based on data I pulled from Capital-IQ, contract manufacturing organizations trade on average at 2.0x projected twelve month revenues (peer-group: Lonza Group, Evonik Industries, Patheon, Catalent, Inc., DaitoPharma). Based on 2016 projected revenues for Nuvo-Commercial of CND$21 million, this equates to a market capitalization of around CND$42 million. The number could grow to CND$62 million in 2016 based on 2017 forecasts.

On an EBITDA basis, the Canadian specialty pharmaceutical industry average (peer-group: Knight Therapeutics, Cipher Pharmaceuticals, Merus Labs, Tribute Pharmaceuticals, BioSyent Inc., Theratechnolgies Inc.) trades at an enterprise value to 2016 EBITDA of roughly 12.5x. Applying this multiple to my projected 2016 EBITDA for Nuvo-Commercial and the shares could be worth a CND$74 million in value today. Nuvo Research (NRI.TO) currently trades with a market capitalization of CND$72 million ($55 million USD). Assuming Nuvo-Commercial is left with roughly CND$5 million in cash from the existing balance of CND$51.8 million as of June 30, 2015 and to me it looks like Nuvo Research investors will get 100% of the value of their shares in just Nuvo-Commercial alone. This means they are getting Nuvo-Development for free.

A Look at Nuvo-Development

At the center of the new Nuvo-Development will be WF10™, the company's Phase 2 drug for the treatment of allergic rhinitis. Also being spun-out to Nuvo-Development will be the rest of the topical and transdermal development stage assets, which includes the Heated Lidocaine/Tetracaine (HLT) Patch, Flexicaine, Pliaglis, DuraPeel, alprazolam patch, risperidone patch, and Ibuprofen foam. Several of these products are approved and generating small revenues - roughly CND$0.4 million in the second quarter 2015 - to Nuvo Research, Inc. The liquid version of WF10, Oxoferin™, approved and on the market in various countries in Europe and Asia for the treatment of chronic wounds, will also be spun-out with Nuvo-Development.

However, the key asset for Nuvo-Development is clearly WF10. The market is assigning little to no value to this drug, likely due to the fact that on January 30, 2015, Nuvo announced disappointing resultsfrom its 184 patient Phase 2b allergic rhinitis study. This was a 16-week, randomized, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of a regimen of five infusions of either WF10 or its main constituents (sodium chlorite and sodium chlorate) relative to saline control (sodium chloride) in patients who suffer from refractory allergic rhinitis with positive skin test to at least one allergen. The study took place at 15 sites entirely in Germany. Endpoints included assessment of total nasal symptom score (TNSS), total ocular symptom score (TOSS), and other secondary endpoints. The study failed to demonstrate statistically significant separation of WF10 versus placebo. This was in stark contracts to previous Phase 2 data that showed very nice separation between the drug and placebo group on both per protocol and intent-to-treat analyses.

In the Phase 2b study, results showed that the WF10 arm demonstrated a reduction in TNSS over the course of the observation period similar to the reduction in TNSS demonstrated in the WF10 arm in the company's previous 2010 Phase 2a proof-of-concept study. The baseline TNSS score was around 7 (entry criteria ≥ 6) and pooled patient data showed a reduction to ~2 at 3, 6, and 12 weeks for the 2010 Phase 2a study. However, in the recent Phase 2b study, the placebo arm demonstrated a reduction in TNSS over the course of the observation period that was significantly greater than expected based on the Phase 2a data. Specifically, in the 2010 study, the placebo group saw a meaningful decline by week 3, but patients got worse as time went on, exiting week 12 with a TNSS score at around 5. This was not the case for the recent Phase 2b. The baseline TNSS score for the most recent Phase 2b study was around 8 according to the conference call held back in January 2015.


Management believes the 2010 trial more accurately illustrates the efficacy of WF10 in the treatment of allergic rhinitis. The company suggests the placebo group in the 2014 trial did not record as high TNSS and TOSS scores compared to the 2010 trial due to a longer enrollment period that started later in the allergy season, varying environmental conditions (more rain during the spring and summer in Germany leading to lower allergic response by patients), and other factors that resulted in some patients in the 2014 trial not being exposed to a high enough concentration of the allergens throughout the trial period.

Still believing that WF10 offers utility in the enormous allergic rhinitis market, Nuvo Research announced a strategic update in April 2015 noting its intension to conduct another Phase 2 study. The new Phase 2 trial is a randomized, double-blind, placebo-controlled, trial to assess the efficacy, safety and tolerability of a regimen of five WF10 infusions. The study is taking place entirely at an environmental exposure chamber (EEC) facility operated by Inflamax Research Inc. in Ontario, Canada. Nuvo received approval from Health Canada to initiate the study in June 2015 and dosing was quickly completed shortly thereafter.

The trial enrolled patients who have confirmed moderate to severe allergy to grass and ragweed pollen. Patients' symptoms to grass and ragweed were recorded prior to commencement of the grass allergy season in an EEC and symptoms will be recorded in the field throughout the grass and ragweed allergy seasons and again in the EEC after completion of the ragweed season. A total of 74 patients were enrolled, less than the original target of 146 but management believes this is sufficient to analyze the safety and efficacy of WF10 in the treatment of allergic rhinitis and to make a decision on its further development. Top-line data are expected late 2015 or early 2016.


Nuvo's external costs of conducting the trial are estimated at approximately CND$4-5 million. As of June 30, 2015, the company has paid CND$2.0 million of costs related to this trial.

Nuvo-Development will be spun-off with the majority of the current cash balance. Above I estimated that Nuvo-Commercial will keep about CND$5 million in cash, or roughly 10% of the current balance. That leaves the other 90% to go to Nuvo-Development, or around CND$40 million assuming burn for the second half of 2015 is similar to the first half of 2015. If the current WF10 Trial is successful, the company plans to continue WF10 development in 2016. The next steps in WF10 development are likely a Phase 2 dose-justification study and an active ingredient identification study. Keep in mind, the current Phase 2 study is dosing five injections of WF10. Nuvo-Development will want to explore potentially fewer doses looking for the minimum efficacious dose. After all, the fewer shots you can give someone, the better! Similarly, WF10 is composed of sodium chlorite and sodium chlorate. Management at Nuvo-Development will want to have explored the full mechanism of action of the drug prior to engaging with the U.S. FDA at the end of 2016 to discuss plans for a pivotal program in 2017. Costs in 2016 to move WF10 forward are likely another CND$8-10 million.

Should the current Phase 2 trial be unsuccessful, the company plans to discontinue WF10 development and it will use its significant cash balance, likely still in excess of CND$40 million, to move other topical and transdermal products forward in 2016 or explore new opportunities by in-licensing mid-to-late stage product candidates. Recall, the goal of Nuvo-Development is to develop drugs to U.S. and Canadian approval, so I suspect that the company will be active on the R&D front in 2016 regardless.

The question for current Nuvo Research shareholders is, What is Nuvo-Development worth? Above I've outlined why I think Nuvo-Commercial can be worth CND$62 million based on industry-average valuation multiples. This is pretty straightforward. Valuing Nuvo-Development is a little more subjective, but what seems clear is that WF10 is targeting a very large market opportunity. For example, according to the American College of Allergy, Asthma & Immunology, over 75 million Americans suffer from allergies, and approximately 17 million American adults and 6.7 million children have seasonal allergies. In 2014, more than 13.4 million visits to physician offices, hospital outpatient departments and emergency departments were due to allergic rhinitis.

This second statistic would seem to suggest, that despite the availability of OTC medications like diphenhydramine (Benadryl®), loratadine (Claritin®), and certirizine (Zyrtec®), a significant percent of Americans are still suffering from seasonal or perennial allergic rhinitis, and might be interested in a new and effective treatment option like WF10. According to The Allergy and Asthma Center, some 10 million Americans are failing OTC or Rx medications and would benefit from allergy shots (subcutaneous immunotherapy); however, only 50% actually follow-through due to the fact that people do not like shots, and subcutaneous immunotherapy is both costly and time consuming. For example, the shots are typically ever 2-4 weeks for 4-5 months and the cost for the first year of treatment can be as much as $1000 (source: WebMD). Plus, you have to know exactly what you are allergic too because the shots are allergen-specific. So if an individual is allergic to grass, ragweed, dust mites, and mold, this might end up requiring four different course of immunotherapy. Yikes! And, according to a 1999 study published in the New England Journal of Medicine, these shots only work if you continue to take them (Zitt M. et al., 1999). Stop taking the shots and most of the time symptoms return immediately.

Nuvo believes WF10 alters the immune system, thus having an immunomodulatory effect that is not allergen-specific. One course of treatment with WF10 may work to curb allergic rhinitis irrespective of the underlying cause of the allergy. Plus, the drug has a short-duration of treatment. This would be an enormous leap forward for patients.

If Nuvo-Development can generate data for the current Phase 2 EEC study that confirms the 2010 Phase 2 study, I think the market will begin to assign real value to WF10. A 2014 marketing report by Psscion Consulting commissioned by Nuvo Research interviewed patients, allergists, and payers and forecasted that WF10 would capture 10-15% of the U.S. refractory allergic rhinitis market. That is a potential 500,000 to 750,000 patients that might be on WF10. At a price of $1,000 for treatment, the potential market opportunity to Nuvo-Development is $500 million to $750 million. I chose $1,000 because this is the current comparable cost of subcutaneous immunotherapy, but I believe this cost may prove to be very conservative given the non-allergen-specific mechanism of action for WF10. A broad-immunomodulating effect would potentially allow for a significantly higher cost while still providing pharmacoeconomic value to both patients and payors.

To value Nuvo-Development, we can apply a risk-adjusted discount to an industry-average multiple on the potential peak sales of WF10 in the U.S. For example, the specialty pharmaceutical industry typically trades at a Price to Sales ratio of around 4x (peer group: Allergan, Valeant, Horizon, Depomed, Shire, Endo). If the current Phase 2 study is successful, Nuvo-Development will probably be in position to initiate the first of two Phase 3 programs in 2017. I believe the company can move rather quickly with these programs and be in position to file for approval of WF10, assuming the data stays looking strong, in 2020. This would put the commercial launch in 2021, and if we assume six years to achieve peak sales, then the company will have sales of around $625 million in 2027. Based on 4x peak sales, Nuvo-Development could be worth $2.5 billion in 2027.

Keep in mind, I'm not saying Nuvo-Development is worth $2.5 billion right now. I'm saying that it could be worth this amount in 2027 if WF10 is successfully commercialized and achieves peak sales of $625 million. To find the value today, we need to apply both a probability-adjustment and time-value discount.

I would consider Nuvo-Development a high-risk specialty pharmaceutical company, and although it will likely be well-capitalized at the time of the spin-off, I still think the cost of capital will be high, and thus the required return for investors will also be high. I am applying a 25% yearly discount rate to the $2.5 billion valuation in 2027. As such, bringing the $2.5 billion value back to present day reduces the value to $170 million. This is what Nuvo-Development would be worth if there was 100% chance WF10 succeeds as I've outlined above. Given that the drug is only in Phase 2 and failed a Phase 2b study in January 2015, I think it is prudent to chop this probability down significantly. At this stage, I would apply only a 20% chance of success as I've outlined above. Under this risk-adjusted assumption, Nuvo-Development is worth approximately $34 million today. If the current Phase 2 trial is successful, I think it is fair to increase the probability rate to 40%, which doubles the value to $68 million.


The company will likely be seeded with CND$35+ million ($25 million USD) in cash, but I also suspect that much of that cash will be earmarked for the future development of the drug. I suspect it will take as much as CND$10 million in funds to bring WF10 to the point where management can sit down for an "end of Phase 2" meeting with the U.S. FDA. Nevertheless, CND$34 million in value for Nuvo-Development, which really includes no additional value for the rest of the topical and transdermal pipeline, is still far more than the market is applying to Nuvo Research, Inc. today.

Conclusion

The current market value for Nuvo Research, Inc. shares is largely based on the product sales and future potential royalties of Pennsaid 2%. As I've outlined above, I think Nuvo-Commercial is worth today roughly what the entire company is trading at right now. Current Nuvo Research shareholders can continue to expect upside in the shares based on Horizon's ramp of Pennsaid 2% in the U.S. and the potential for new markets with the drug like Canada and Europe. The success of the current Phase 3 study being conducted in Germany will be key to unlocking more potential upside for Nuvo-Commercial in 2016.

With Nuvo-Development, shareholders are receiving a call option on the outcome of the current Phase 2 environmental exposure chamber study being conducted in Canada right now. Nuvo management believes there is tremendous upside if this trial succeeds. I agree, and as I've outlined above, Nuvo-Development can become a potential multi-billion dollar company based on the success of WF10. As of right now, this upside is being masked by investor focus on the commercial side. The impetus for the spin-off is to unlock this value.

My valuation work for the two separate companies tells me if you own Nuvo Research today, you are likely to see almost all the value be maintained in the shares of Nuvo-Commercial. Nuvo-Development, whatever the market decides to value this company at, is essentially free. That's why I referred to it above as a call option. I think it should be worth $34 million today, but investors can play with the numbers themselves by adjusting the peak sales, discount rate, and probability of success accordingly. Remember though, Nuvo-Development will likely be spun-off with CND$35+ million in cash, so my value of CND$34 million for WF10 looks conservative.

My work tells me the spin-off could unlock about 30% of hidden value in the shares for investors. That type of upside is very attractive in this market, and it comes with what I see as limited risk given that the trajectory of Pennsaid 2% at Horizon looks solid and the cash position protects on the downside should WF10 fail. As noted above, Nuvo Research will distribute an information circular in early November 2015 to shareholders of record. This circular will further elaborate on the strategy for each company and likely provide some initial financial guidance. The improved visibility could act as a nice catalyst for the shares.

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