Investment process: Leveraging sector expertise
BPCR’s investment strategy relies on ongoing screening of a large number (>200) of potential opportunities. Individual investment selection is based on detailed analysis of the underlying royalty collateral, including the clinical utility of the product, competitive landscape, IP situation, pricing, reimbursement (insurance and Medicaid/Medicare coverage), marketer’s strength, as well as the opportunity’s safety record, physician adoption and sales history. In performing this analysis, Pharmakon Advisors relies in part on Royalty Pharma’s internal analyst team (seven analysts with a medical degree or background in biochemistry, biology and material sciences) based on the shared services agreement it has signed with Royalty Pharma. Importantly, in some instances, it may benefit from Royalty Pharma’s solid understanding of the underlying asset. This is developed while investing in the royalty interest at an earlier stage than BPCR. Pharmakon will conduct primary market research and may also use third-party market research. The future sales potential of respective drugs is evaluated based on direct discussions with external experts and leading physicians. Moreover, the investment manager may rely on market research in the form of physician studies to examine safety, familiarity, usage and acceptance of respective products by practising doctors. Finally, outside counsel may be leveraged to evaluate IP rights and the patent estate of the royalty collateral.
Pharmakon Advisors also examines the structure of royalty investments. It pays particular attention to the expected yield and duration, quality (ie, strength and enforceability) of collateral, coverage ratios (calculated as commercial licence value to the amount of debt outstanding), priority of payments, as well as cash flow projections and their impact on expected maturity and duration.
In the case of senior secured loans and unsecured debt, apart from examining the products marketed by the borrower, the fund manager also evaluates its credit profile and how the potential investment is structured. In terms of the borrower’s credit metrics, it takes into consideration expected product margins, coverage ratios (projected free cash flow to total debt and/or EV to debt), access to equity markets to raise fresh capital, quality of the management team, production capacity, as well as overall capital structure and other existing liabilities. The analysis of the investment structure is largely concentrated on the expected yield and duration, quality of collateral, covenants, call protections, structural yield enhancement (eg, additional coupons linked to sales) as well as access to liquidity in the case of listed stocks.
BPCR seeks investments with predictable cash flows and significant downside protection. Importantly, when evaluating new investment opportunities, BPCR is solely focused on approved products, thus avoiding the risks associated with drug development and clinical trials. If the borrower, in addition to approved drugs, also has products in late-stage clinical trials, these are not assumed to reach the market, hence giving BPCR a safety margin. To further minimise the risk, BPCR may include revenue and profitability covenants to loan agreements or provide debt funding in tranches depending on product sales ramp-up (see the recent Lexicon deal described in the next section). Following investment, BPCR monitors its assets regularly and remains in contact with the borrower’s management. Moreover, the investment manager and BPCR’s board hold quarterly meetings to discuss the level of exposure to market risk at a portfolio level.
Current portfolio positioning
Part of the company’s portfolio (c 18% as at end March 2018) consists of the following seed assets acquired in conjunction with the IPO:
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BioPharma III Holdings (limited partnership interest) represents a portfolio which, as at end-March 2018, consisted predominantly of three senior secured loans and one capped royalty (see Exhibit 6). BioPharma III has a defined investment period that concluded on 24 August 2015, thus the entity is no longer permitted to acquire new assets. Also, there is no outstanding commitment to provide additional funding to any of the existing borrowers. BPCR’s current share in BioPharma III is 46%.
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RPS BioPharma Investments (senior secured loan): the note is secured by 10 royalty interests, which are used by 21 pharmaceutical products. In the issue prospectus published last year, BPCR indicated that the top three royalty interests represented over 65% of the total projected royalty payments to be received by RPS. The Emtricitabine and Humira franchises are the largest contributors, with a combined 46.6% of the overall expected royalty streams (see Exhibit 5). Key terms of the RPS note include maturity upon the earlier of: repayment of the outstanding aggregate principal and interest accrued on such amounts; or 30 June 2026. However, the RPS note is likely to be fully repaid in 2019, according to BPCR.
Exhibit 5: RPS note – royalty interest structure (as per projected royalty streams)
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Source: BioPharma Credit’s issue prospectus
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Both RPS and BioPharma III are considered related entities of BPCR due to a principal of the investment manager having significant influence over each entity. BioPharma III is an investment vehicle managed by Pharmakon Advisors, whereas RPS is managed by an affiliate of Pharmakon.
BPCR’s portfolio structure at end March 2018 is presented in Exhibit 6. It does not reflect the Onglyza/Farxiga royalty transaction, which is discussed later in the report. Another deal that is not incorporated is the US$194m, five-year senior secured loan agreement announced on 1 May with Sebela BBT Holdings, a subsidiary of Sebela Pharmaceuticals, which is a commercial-stage, private, specialty pharmaceutical company. The company has pro forma annual sales of c US$250m in dermatology, gastroenterology and women’s health and is a marketer of multiple patent-protected specialty drugs. Importantly, the loan will have a high single-digit floating coupon and will be amortized starting after Q318. Sebela’s leverage is below 4x EBITDA.
The portfolio structure is also not updated for the C shares issue completed in April this year. Finally, BPCR purchased 2.5% senior unsecured convertible notes issued by Depomed with a face value of US$23.5m in September and October 2017, and subsequently sold its entire position before the end of 2017, generating a net gain of US$2.5m and an IRR of 154%.
Exhibit 6: Portfolio composition as at end March 2018
Counterparty/ Borrower |
Asset |
Underlying products |
Fair value (US$m) |
Expected maturity |
Coupon/royalties |
Fees and other |
% of net assets |
BioPharma III |
Limited partnership interest |
- |
73.1 |
- |
- |
- |
8% |
Depomed |
Senior secured loan |
Nucynta, Gralise, Cambia, Zipsor, |
N/A |
April 2022 |
10.75% (fixed) |
2.25% up-front funding fee |
N/A |
Valneva |
Senior secured loan |
Ixiaro |
N/A |
2018 |
9.5% coupon plus 2.0-2.6% royalty of Valneva’s share of Ixiaro/Jespect sales |
- |
N/A |
iRhythm |
Senior secured loan |
Zio Patch |
N/A |
2021 |
N/A |
Amortisation: interest-only for the first four years; straight-line for the last two years |
N/A |
Vivus |
Capped royalty |
Qsymia |
N/A |
April 2018 |
25% of quarterly sales of Qsymia (subject to quarterly caps) |
- |
N/A |
RPS |
Senior secured loan |
21 products |
87.5 |
2019 |
12% (fixed) |
- |
10% |
Lexicon |
Senior secured loan |
Xermelo, sotagliflozin |
124.5 (first tranche) |
2022; Make-whole: 3 years |
9% (fixed) |
Amortisation: principal amount five years post-funding date; prepayment: 2%/1% before fourth or fifth anniversary of tranche A |
14% |
Tesaro |
Senior secured loan |
Zejula, Varubi |
222.0 (first tranche) |
December 2024; Make-whole: two years |
Libor + 8.0% (tranche A), Libor + 7.5% (tranche B); Libor is subject to a floor of 1% and certain caps |
Funding fee: 2% on each tranche Amortisation: two-year interest only then 3% quarterly; prepayment: 3%/2%/1% before second/third/fourth anniversary of tranche A |
24% |
Novocure |
Senior secured loan |
Optune |
150.0 |
2023 |
9% (fixed) |
|
16% |
Other |
- |
- |
3.0 |
- |
- |
|
- |
Cash |
- |
- |
249.2 |
- |
- |
|
27% |
Total net assets |
- |
- |
909.3 |
- |
- |
|
100% |
Source: BioPharma Credit, Edison Investment Research
Within the current BioPharma III portfolio, the most important asset in terms of sales potential is Nucynta (tapentadol), an opioid-based drug for severe pain, available in both immediate and extended release (ER) forms. Depomed, which has a proprietary technology to optimise oral drug discovery, acquired the US Nucynta franchise from Johnson & Johnson in 2015 but, as part of restructuring in December 2017, sublicensed it to the pain management specialist Collegium Pharmaceutical for exclusive US marketing. The agreement consisted of a US$10m upfront payment, plus a minimum annual licence fee to Depomed of US$135m plus double-digit royalties on net sales above US$233m per year for the first four years. Subsequently, Collegium will pay double-digit royalties on all net sales. We note that Collegium can terminate the deal after 12 months with a 12-month notice period and a payment of US$25m.
Sales of US Nucynta were US$240m in 2017 (US$281m in 2016) and clearly face challenging headwinds in the US opioid market, with stringent regulations to reduce abuse leading to modest market growth forecasts of around 3% pa to 2025 (Transparency Market Research). In addition, short-term supply issues due to Hurricanes Irma and Maria have affected Nucynta ER sales, although these were already resolved in March 2018. Despite this, we believe Collegium is well positioned to stabilise the brand and market the Nucynta franchise from mid-February 2018 with its existing retail and hospital field forces to 10,000 pain specialists. Focusing on ‘responsible pain management’, it markets Xtampza ER (oral oxycodone for severe pain) and the Nucynta products should have salesforce synergies with and broaden its pain portfolio across a wide range of pain conditions.
Depomed also has a neurology portfolio consisting of three remaining products (Gralise, Cambia and Zipsor), which have been marketed since 2009-11. These are formulations of generic molecules offering delivery or therapeutic advantages and Depomed has recently expanded its neurology salesforce to focus on this franchise and potentially add neurology-based product acquisitions. Combined sales in 2017 were US$126m and company guidance is for stable sales in 2018.
As of March 2018, US$267m of generated cash has been used to partially pay down the US$575m senior secured loan with the current amount outstanding at US$308m. In our opinion, the combined sales/royalty income from Nucynta and the continuing neurology franchise more than covers the interest and principal payments associated with Depomed’s remaining loan. Depomed intends to refinance the loan in H218.
Valneva, iRhythm and Vivus
Other products underpinning the investments in BioPharma III include Ixiario (marketed by Valneva), a Japanese encephalitis (JE) vaccine launched in 2009 for travel and military use. It is the only approved JE vaccine in the US. Sales in 2017 were US$73m, and in November 2017 Valneva signed a one-year contract with the US Department of Defense for US$39.6m to supply Ixiaro.
iRhythm markets the heart monitor device Zio Patch, which backs a senior secured loan. The US$1.6bn ambulatory cardiac monitoring US market is being driven by an aging population and need by payers for outpatient monitoring to reduce costs. Although there are competing portable devices available (eg, Nuvant from Medtronic), Zio Patch appears to have gained traction with Medicare and other key payers. The main advantage of Zio Patch appears to be its convenient design versus the conventional Holter monitor and high data yield for comparatively low cost. Sales in 2017 were US$99m and forecast to grow at c 30% per year to 2020.
Vivus paid a capped royalty associated with Qsymia, a combination drug for weight loss management in obese adults. However, it was already repaid by end-April this year.
The RPS portfolio includes royalties on pharmaceuticals used in the treatment of autoimmune disorders, HIV/AIDS, neurological disorders and diabetes, and on other products. Many of them have been or are 'blockbusters' and in 2015, total sales of these products were c US$50bn. The three largest components of the RPS portfolio are royalties from:
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The emtricitabine franchise (Atripla, Truvada, Emtriva, Complera, Stribild, Genvoya, Descovy and Odefsey), 23.5% of total projected royalty payments.
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Humira, 23.1% of projected royalties.
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DPP-IV franchise (Januvia/Janumet, Galvus/Eucreas, Onglyza/Komboglyze, and Nesina), 18.8% of projected royalties.
The emtricitabine franchise faces ongoing challenges in the form of price pressure as the manufacturer Gilead is called to improve access to these HIV drugs, as well as generic threats to the earlier combinations (Atripla, Truvada and Emtriva). As a way of protecting the franchise, the company is therefore promoting the uptake of the newer combinations (Genvoya, Descovy and Odefsey) and is developing Bictegravir/F/TAF (which contains emtricitabine) in Phase III.
The best-selling drug globally, AbbVie’s Humira, which posted sales in 2017 of over US$18bn, faces the potential threat of FDA-approved biosimilars from companies such as Amgen, Samsung and Boehringer Ingelheim. However, protracted legal wrangling over the 100+ patent estate have kept biosimilars off the market so far, with Amgen agreeing not to launch until October 2018 in Europe and January 2023 in the US.
Although the DPP-IV inhibitor class of diabetes drugs suffered with safety questions a few years ago, and still face competition from the sodium-glucose co-transporter 2 (SGLT2) class, Merck’s Januvia/Janumet remains a key component of diabetes treatment and posted US$5.9bn in sales in 2017. This is a class likely to experience price pressure from payers.
Tesaro loan: Zejula and Varubi
On 21 November 2017, BPCR entered into a US$500m loan agreement with Tesaro to be funded in two tranches: tranche A, US$300m (of which US$222m is attributable to BPCR) and tranche B, US$200m (US$148m provided by BPCR, prior to December 2018). The first tranche has a floating interest rate at Libor +8%, while the second has a rate of Libor +7.5%, with both being subject to floors and caps.
In the case of Tesaro, the underlying products for the loan are Zejula (niraparib), a PARP inhibitor to treat recurrent ovarian cancer, and Varubi (rolapitant), an antiemetic agent to treat cancer nausea. Zejula was approved in the US in March 2017 and in the EU in November 2017. Sales in 2017 were US$109m, with Q417 sales at US$43m (translating into a run rate of c US$170m). Tesaro’s guidance for 2018 and 2020/21 stands at US$255-275m and US$700-800m, respectively. However, we remain slightly more cautious and would look to watch uptake through 2018-19. Zejula will face significant competition in the PARP inhibitor class from Clovis Oncology's Rubraca and particularly AstraZeneca's Lynparza, as AstraZeneca seeks to expand the Lynparza label into maintenance treatment BRCA-negative breast cancers and BRCA (a tumour-suppressor gene) mutated mainly breast cancers.
In contrast, Varubi (rolapitant) had sales of only US$12m in 2017 following its launch in 2016, and safety concerns affecting the IV form (anaphylaxis) have led to a suspension of marketing. The oral form of Varubi faces competition from generic forms of Merck’s Emend (prepitant). According to the company, strategic alternatives will be sought and the product may be out-licensed.
Importantly, the first tranche of the Tesaro loan has already been drawn and constituted c 24% of BPCR’s net assets as at end-March 2018. The trust has recently completed the placement of its C shares, raising US$163.8m of gross proceeds, which translates into an increase in net assets to c US$1.1bn. If the second tranche of the Tesaro loan is drawn as well, BPCR will need to raise an additional US$160m or sell a portion of the Tesaro loan to remain beneath the 30% threshold after funding tranche B.
Lexicon loan: Xermelo and sotagliflozin
In the case of the recently granted loan to Lexicon, the underlying products are Xermelo (telotristat) and sotagliflozin. The former was recently approved for the treatment of carcinoid syndrome diarrhoea, in February 2017 in the US and September 2017 in Europe. Ipsen has licensed marketing rights in all territories apart from the US and Japan, where Lexicon retains rights. Following launch, US sales were US$15m in 2017 and expected to grow to over US$200m by 2022 (Evaluate consensus estimates).
Sotagliflozin is an oral, dual SGLT1/SGLT2 inhibitor in Phase III clinical trials for type 1 and type 2 diabetes. Lexicon has licensed the product to Sanofi worldwide for US$300m upfront, up to US$430m for development and regulatory milestones and up to US$990m for sales milestones. Sanofi filed for US registration on 26 March 2018. Although this is a highly competitive class (with JNJ’s Invokana, AstraZeneca’s Farxiga, Boehringer Ingelheim’s Jardiance and Merck’s Steglatro), existing drugs target SGLT1 only. Consequently, sotagliflozin may be able to carve its own niche. However, we have limited visibility in terms of the uptake curve at the moment and AstraZeneca has also published data showing benefit in type 1 diabetes for Farxiga. Nevertheless, the field is still relatively wide and peak sales potential could exceed US$1bn by 2025.
This five-year US$200m loan bears interest at 9.0% per year and is to be funded in two tranches: tranche A US$150m (of which US$124.5m is attributable to BPCR) was already drawn down and tranche B US$50m (of which US$41.5m is provided by BPCR), with tranche B to be drawn by 30 March 2019 at Lexicon’s option, subject to previous-quarter Xermelo sales being greater than US$25m.
Bristol Myers Squibb funding: Onglyza and Farxiga
In December 2017, BPCR also purchased a 50% interest (sharing the investment 50:50 with Royalty Pharma Investments) in a royalty stream from Bristol Myers Squibb linked to worldwide sales of two diabetes drugs, Onglyza and Farxiga, marketed by AstraZeneca, and related products. The potential funding is US$140-160m over 2018-2020 and is expected to generate high-single digit returns per year.
Sales of Onglyza (saxagliptin) attributable to AstraZeneca peaked in 2014 at US$820m and subsequently declined to US$611m in 2017 amid concerns around increased heart failure risk. The EvaluatePharma consensus forecast indicates an average sales decline of c 6.5% over the next five years. This reflects the pressures on the dipeptidyl peptidase-4 class and the movement of patients to diabetes therapies with documented cardiovascular (CV) benefits.
In contrast, Farxiga (dapagliflozin) sales showed good momentum following its US launch in 2014, reaching US$1,074m in 2017 (up 29% y-o-y), with an expected five-year sales CAGR of 11% (EvaluatePharma consensus). AstraZeneca continues to prioritize commercial support for Farxiga over Onglyza, reflecting the competitive SGLT2 inhibitor class. Recent launches in the same class include JNJ’s Invokana (canagliflozin, approved 2013), Eli Lilly/ Boehringer Ingelheim’s Jardiance (empagliflozin, approved 2014) and Merck’s Steglatro (ertugliflozin, approved December 2017). Outcomes data showing CV benefit expected late 2018 may support Fargixa market share. Although there are also safety concerns linking SGLT2 inhibitors to diabetic ketoacidosis, kidney problems and bladder cancer, any revenue impact is unlikely to materially affect interest repayment.
The company’s sole product is Optune, a wearable device for the treatment of glioblastoma multiforme (GBM) that employs electric fields tuned to specific frequencies to disrupt cancer cell division. Originally approved in 2011 for GBM that has relapsed or progressed after treatment, it was approved in 2015 for use with conventional temozolomide chemotherapy in newly diagnosed adult patients. Phase III data (EF-14 in 695 patients) demonstrated a two-year survival rate of 43% for patients treated with Optune plus temozolomide (TMZ), versus 30% for patients treated with TMZ alone.
Novocure is driving commercial adoption of Optune in GBM patients in active markets and establishing access in new markets such as Japan. It has been launched in US, Germany, Switzerland and Israel (where a total of around 17,000 cases are diagnosed per year) and generated total sales of US$177m in 2017. The cost of around $22,000 per year, per patient is largely privately funded, although Novocure is in active discussions for reimbursement in several countries, including the US. In Japan, a national reimbursement contract was signed in Q417 and launch is underway.
Global peak sales potential of US$400-500m by 2022+ is achievable given the pricing and lack of alternative treatments for this difficult-to-treat cancer. Sales could be expanded by approval in other solid tumours that have larger market potential (brain metastases in non-small cell lung cancer, pancreatic and ovarian cancer) although Phase III data will not be available until 2021. The Optune device may also have ability to potentiate other GBM chemotherapies and is being trialled in combination with Celgene’s marizomib.
Novocure’s original US$100m senior secured loan provided by BioPharma III was repaid on 7 February 2018 using proceeds from a five-year US$150m senior secured loan agreement with BPCR, with the balance being used for working capital funding. The loan bears interest at 9.0% per year, payable quarterly in arrears. We consider Optune revenues are sufficient to cover the payments associated with the loan.