Surufatinib on track for potential 2020 China approval
Update | 18 June 2019
Hutchison China MediTech (Chi-Med) is one step closer to the commercialisation of its first wholly owned drug, surufatinib, in China. Early termination of the Phase III SANET-ep study in extra-pancreatic neuroendocrine tumours (epNET) – as it had already met its primary endpoint of progression-free survival (PFS) at the planned interim analysis – brings forward the timing of potential first surufatinib approval by c 12 months. While full SANET-ep data will not be available until presentation at a future scientific conference, this result enables Chi-Med to seek a pre-NDA meeting with the China NMPA to discuss next steps in the regulatory process. Reviewing our surufatinib assumptions, we now assume a 2020 approval/launch in non-pancreatic NET. Our upgraded valuation is $5.14bn ($38.55/ADS) or £3.95bn (£5.93/share).
|Year-end: December 31||2017||2018||2019E||2020E|
|Adj. PBT (US$m)||(53.5)||(86.7)||(205.6)||(202.0)|
|Net Income (US$m)||(23.0)||(71.3)||(170.6)||(164.4)|
|Earnings per ADS (US$)||(0.22)||(0.57)||(1.31)||(1.26)|
|Adj. EBITDA (US$m)||(17.2)||(69.7)||(163.9)||(159.5)|
18 June 2019
|Price (US ADS) (UK share)||$26.55|
|Shares in issue (ADS)|
Hutchison China MediTech is a Hong Kong headquartered biopharma with an established Commercial Platform in China, and a diverse pipeline of first-in-class/best-in-class selective oral tyrosine kinase inhibitors (Innovation Platform). Its pipeline, discovered in-house, is in development for the China and global oncology markets.
+44 (0) 20 3637 5041
Mick Cooper PhD
+44 (0) 20 3637 5042
+44 (0) 20 3637 5043
Surufatinib is on track to become the first of Hutchison China MediTech’s (Chi-Med) wholly owned drugs to reach the market in China. The pivotal SANET-ep trial in advanced extra-pancreatic neuroendocrine tumours (epNET) has been stopped early for efficacy at the planned interim analysis following the IDMC (Independent Data Monitoring Committee) determination that the mPFS (median progression free survival) primary endpoint had been met. Full results will be presented at a future scientific conference. The next step for Chi-Med is a pre-NDA (new drug application) meeting with the China NMPA (National Medical Products Administration) to discuss the surufatinib NDA process. We believe that there is now potential for a 2019 NDA filing and 2020 approval for surufatinib in epNET. Updating our assumptions increases our valuation to $38.55/ADS ($5.14bn) or £5.93/share (£3.95bn) up from $35.57/ADS ($4.74bn) or £5.47/share (£3.65bn) previously.
Surufatinib (formerly HMPL-012 or sulfatinib) is Chi-Med’s most advanced unpartnered asset and the company is prioritising securing a rapid first approval in China in all types of NET. NET is an umbrella term for tumours that develop from cells in the endocrine and nervous systems, most commonly in the digestive and respiratory tracts. It can be split into two distinct populations based on molecular genetics and treatment options. Non-(extra)-pancreatic NET (epNET) is the more common representing c90% of NETs; the remainder are pancreatic NET (pNET).
The pivotal 273-pt SANET-ep trial is the first NET study to complete. A second Phase III trial, SANET-p, in pNET, is enrolling with an interim analysis planned for late 2019. At this stage, we choose to err on the side of conservativism and assume no read through from the SANET-ep interim result to SANET-p.
Our base case assumption for SANET-ep was that it would run to completion, with full enrolment by end-2019 and top-line data in mid-2020. The interim stop for efficacy is a positive development, which by our assessment results in a c 12 month benefit to timelines, suggesting NDA filing is likely in H219, with potential China launch by Chi-Med’s own commercial team in late-2020.
The approval timeline for fruquintinib (Elunate), Chi-Med’s first commercial product, provides a precedent which guides our revised assumptions for the surufatinib regulatory process. Fruquintinib was launched in 3L colorectal cancer (CRC) in November 2018 by partner Eli Lilly following NMPA approval in September 2018. The fruquintinib NDA was submitted within 4 months following top-line data from the pivotal FRESCO trial. It took a further 15 months for approval to be granted.
The earlier nature of SANET-ep data suggests some additional time (we assume an extra month) may be needed for Chi-Med to prepare the surufatinib NDA submission. However, as it will be manufactured at the same GMP certified facility in Suzhou as fruquintinib, we might expect a more rapid CMC review given that several components are already validated. Consequently, we presume this 15 month post-NDA approval timeline may be shorter for surufatinib.
Chi-Med has not disclosed the mPFS achieved at the SANET-ep interim analysis, as trial data will be presented at a future scientific conference. A recap of the Phase II China NET data (summarised in Exhibit 1) gives an indication of the magnitude of response that might be expected. In particular, this trial reported a 13.4 month mPFS for the epNET population (n=40). While this is shorter than the 19.4 months for pNET patients (n=41) and 16.6 month mPFS for the overall trial (n=81), it does highlight that in general NETs are slow growing tumours compared with other tumour types. This means NETs are associated with a relatively long duration of survival, and NET patients are typically on drug therapy for longer.
NET is the first of many opportunities for surufatinib. Its development programme is focused on indications with high unmet need and with the potential for a rapid path to market given the relative rarity of the cancer types targeted and limited treatment options.
Surufatinib is a novel selective oral small molecule TKI (tyrosine kinase inhibitor) with an angio-immuno kinase profile which differentiates it from other VEGFR (vascular endothelial growth factor receptor) TKIs. In addition to VEGFR, surufatinib targets FGFR (fibroblast growth factor receptor) and CSF-1R (Colony stimulating factor-1 receptor). This profile supports development both as a multi-functional monotherapy agent and in combination with checkpoint inhibitors. Ongoing and planned clinical trials for China and Global are presented in Exhibit 2.
Surufatinib’s ability to inhibit tumour associated macrophage (TAM) production facilitates generation of a PD-1 induced immune response. This feature is being explored under Chi-Med’s PD-1 monoclonal antibody collaborations (announced November 2018), which include a global partnership with Shanghai Junshi for Tuoyi (toripalimab), and a China-only deal with Taizhou Hanzhong for HX008.
In addition to NDA filing for epNET, news flow for surifatinib during 2019 includes the interim analysis of the Phase III SANET-p trial, and the submission for publication of results of the China Phase Ib/II BTC study.
Fruquintinib is the first of Chi-Med’s internally developed TKIs to be approved and commercialised in China. Consequently, not only does it provides a guide for the potential regulatory timeline for surufatinib, but it is also a focus for investors and we use this opportunity to provide a brief status update.
We note that recent filings connected to Chi-Med’s proposed Hong Kong IPO provide unaudited Q119 revenues. These report ‘collaboration revenue’, ie royalty income from partner Eli Lilly in relation to fruquintinib. Royalty receipts stood at US$978k in Q119 vs US$261k in the first five weeks that fruquintinib was on the market (from November 2018). The growth in royalty income is a promising start; however, at present this is generated from out-of-pocket expenses supported by patient assistance programmes. We expect that once fruquintinib secures reimbursement on the National Reimbursement Drug List (NRDL) there will be a major inflection point in sales/royalties, although there is no firm guidance for when this may occur.
Like surufatinib, fruquintinib is in development for multiple tumour types, including in combination with checkpoint inhibitors. Various life cycle indications are in planning. Three tumour types have been or are currently being evaluated in Phase III, all of which should generate near-term newsflow.
Clearly, the impressive outcome of the SANET-ep trial means that our forecast timelines for approval and marketing will be accelerated. We have reviewed our model to reflect the probable benefit of a c 12 months improvement in the surufatinib approval timelines compared to our previous expectations. We have also taken the opportunity to fine-tune our model for other relevant factors, most noticeably the current multiples for Chinese-listed healthcare companies.
The positive effect in our forecast time to approval (and hence launch) and the improvement in success probabilities (with the likelihood of success up from the 65% employed to reflect the previous Phase III status to the 90% we typically employ for pre-approval stages) comfortably offsets the small decrease in our valuation of the China Healthcare businesses. Our valuation methodology is detailed in our Initiation note (February 2019) and, as noted there, we strive to employ conservative assumptions throughout our valuations
Updating our assumptions increases our valuation by 8.4% to $38.55/ADS ($5.14bn) or £5.93/share (£3.95bn) up from $35.57/ADS ($4.74bn) or £5.47/share (£3.65bn) previously. We would highlight that this is a pre-money valuation pending the proposed Hong Kong IPO and global placement. We will further update the model again once the result of the proposed fund-raise is known.
Trinity Delta Research Limited (“TDRL”; firm reference number: 725161), which trades as Trinity Delta, is an appointed representative of Equity Development Limited (“ED”). The contents of this report, which has been prepared by and is the sole responsibility of TDRL, have been reviewed, but not independently verified, by ED which is authorised and regulated by the FCA, and whose reference number is 185325.
ED is acting for TDRL and not for any other person and will not be responsible for providing the protections provided to clients of TDRL nor for advising any other person in connection with the contents of this report and, except to the extent required by applicable law, including the rules of the FCA, owes no duty of care to any other such person. No reliance may be placed on ED for advice or recommendations with respect to the contents of this report and, to the extent it may do so under applicable law, ED makes no representation or warranty to the persons reading this report with regards to the information contained in it.
In the preparation of this report TDRL has used publically available sources and taken reasonable efforts to ensure that the facts stated herein are clear, fair and not misleading, but make no guarantee or warranty as to the accuracy or completeness of the information or opinions contained herein, nor to provide updates should fresh information become available or opinions change.
Any person who is not a relevant person under section of Section 21(2) of the Financial Services & Markets Act 2000 of the United Kingdom should not act or rely on this document or any of its contents. Research on its client companies produced by TDRL is normally commissioned and paid for by those companies themselves (‘issuer financed research’) and as such is not deemed to be independent, as defined by the FCA, but is ‘objective’ in that the authors are stating their own opinions. The report should be considered a marketing communication for purposes of the FCA rules. It has not been prepared in accordance with legal requirements designed to promote the independence of investment research and it is not subject to any prohibition on dealing ahead of the dissemination of investment research. TDRL does not hold any positions in any of the companies mentioned in the report, although directors, employees or consultants of TDRL may hold positions in the companies mentioned. TDRL does impose restrictions on personal dealings. TDRL might also provide services to companies mentioned or solicit business from them.
This report is being provided to relevant persons to provide background information about the subject matter of the note. This document does not constitute, nor form part of, and should not be construed as, any offer for sale or purchase of (or solicitation of, or invitation to make any offer to buy or sell) any Securities (which may rise and fall in value). Nor shall it, or any part of it, form the basis of, or be relied on in connection with, any contract or commitment whatsoever. The information that we provide is not intended to be, and should not in any manner whatsoever be, construed as personalised advice. Self-certification by investors can be completed free of charge at www.fisma.org. TDRL, its affiliates, officers, directors and employees, and ED will not be liable for any loss or damage arising from any use of this document, to the maximum extent that the law permits.
Copyright 2019 Trinity Delta Research Limited. All rights reserved.