The cancer burden is growing globally. Each year >18 million people are diagnosed, nearly 10 million die and the estimated economic cost exceeds $1 trillion. From early diagnosis to late-stage disease, cancer care often involves inappropriate or unnecessary interventions that drive costs but provide limited clinical benefit. Coupled with an increased understanding of cancer biology and rapid technological advances, this has been driving momentum for precision medicine, leading to patient and societal benefits. The use of biomarkers and sophisticated diagnostics is facilitating early intervention through robot-enabled minimally invasive surgery and locally delivered radiotherapy. Immuno-oncology has revolutionised cancer care, with the focus now on identifying combinations that further improve long-term outcomes. Liquid biopsies and companion diagnostics are increasingly being used to personalise therapy.
Companies: VSC ABT ABBV AFMD A GOOGL AMGN AZN BCART BMY CVRS EKTAB EXAS GSK ILMN IPH ISRG IBAB JNJ MDXH MDG1 MDT MRK MYGN NSTG NOVN OCX PFE QGEN RAYB ROG SAN SGEN TMO TRXC TNG VAR VCYT VNRX XNCR ECX IMM
4SC has reported progress with both its clinical-stage assets – resminostat, a broad spectrum HDAC inhibitor, and domatinostat, a specific Class 1 HDAC inhibitor. In January 2019, the investigator-led Phase II EMERGE study was initiated, which is testing domatinostat in gastrointestinal cancer. 4SC has developed a broad development programme for this drug, which will include several strategic options to commercialize the asset including out-licensing based on data from multiple Phase II studies and internal pivotal development for Merkel cell carcinoma. In January 2019, the resminostat RESMAIN study received a second positive DSMB safety review and the top-line results are expected in H120. 4SC remains well funded with cash of €30.8m at end-Q318, which should fund operations into 2020. Our valuation is virtually unchanged at €328m or €10.7/share.
We have recently carried out a review of our Corporate Sponsored Research Coverage. Following this review we have decided to terminate 4SC AG's formal agreement and to discontinue research coverage of 4SC AG with immediate effect.
During the Q218 results call, 4SC management announced that with current funds, it plans to initiate some of its additional domatinostat trials including the pivotal Merkel-cell carcinoma (MCC) study and a Phase II skin cancer checkpoint combination study. 4SC will provide further detail in H218. The SENSITIZE study (Phase Ib/II, melanoma) is on track in Europe (data H119), while a new IND will allow expansion of the study into the US in 2019. The EMERGE study (Phase II, GI cancers) is now expected to initiate in Q318 (previously H118). The multiple domatinostat studies in H218/H119 will provide several R&D catalysts while investors wait for pivotal RESMAIN study data. Enrolment for the RESMAIN study (CTCL) continues in Europe and Japan (100/150 patients by end-2018), and top-line data are now expected in H219 (previously H119). Due to this modest delay, we now forecast resminostat launch in 2021 (previously 2020), and therefore slightly lower our valuation to €327m or €10.7/share (vs €11.4/share).
4SC's H1/2018A report published today indicates that the company remains on track, but is fundamentally undervalued. As detailed in our note of the 16th July, financed into 2020E, the company's current valuation is largely justified by its pivotal stage resminostat ("RESMAIN") programme. It takes little or no account of the potential value of the domatinostat currently in Phase II in combination with the immune checkpoint inhibitor ("ICI") pembrolizumab for melanoma. First interim data from the domatinostat ("SENSITIZE") trial due in H1 should provide a substantial catalyst for the stock now trading at less than half of its early 2018 peak. Preclinical studies and positive data from sub-optimally dosed drugs of the same class support a synergy between immune checkpoint inhibitors ("ICI") and domatinostat. We maintain and reiterate both our OUTPERFORM recommendation and TP of €10.
With the share price down over half from it's early 2018 peak, 4SC's valuation looks justified on the basis of it pivotal resminostat programme alone. The market ascribes little value to the immunotherapy combination programme with dominatostat now in Phase II. Although sentiment toward immuotherapy has deteriorated in the wake of the negative Incyte-Merck epacadostat ("IDO-1") data, we contend the dominatostatpembrolizumab ("pembro") immunotherapy combo still holds promise. Preclinical studies and data from sub-optimally dosed drugs of the same class support a synergy between immune checkpoint inhibitors ("ICI") and dominatostat. Interim data expected from the dominatostat-pembro phase II ("SENSITIZE") melanoma study in H2/2018E could provide a substantial catalyst for the stock. We reiterate our OUTPERFORM recommendation and our target price of €10.
Yakult, 4SC’s development partner for resminostat in Japan, has reached two clinical development milestones. First, just two weeks after it joined 4SC’s pivotal RESMAIN study (n=150) in CTCL, the company recruited the first patient in Japan. Top-line results from the RESMAIN trial are expected in mid-2019. In addition, Yakult initiated its own Phase II study in biliary tract cancer (n=100) in combination with S-1 chemotherapy. S-1 is widely used in Japan and other Asian countries to treat patients following relapse after a 1st line chemotherapy regimen. The final data readout is expected in mid-2020. Meanwhile, at the AACR Annual Meeting in April, 4SC presented new preclinical data supporting the use of its second lead product, 4SC-202 in combination with various immunotherapy agents. Our valuation is virtually unchanged at €348 or €11.4/share.
4SC's Japanese partner Yakult Honsha's (Yakult) decision to join the RESMAIN study looks a significant endorsement of the resminostat programme. While CTCL (Cutaneous T-Cell Lymphoma) is probably not itself a substantial opportunity in Japan, with Yakult's prime focus on the more Asian-prevalent biliary cancer, it clearly demonstrates commitment from a partner that already knows the product well. Outside Japan, prospects for 4SC also look bright. Its clinical programmes appear to be progressing well. Strong news flow, including the first read out from its proof-ofconcept phase II for 4SC-202 in H2/2018E, should maintain momentum for the stock over the next 6 months and beyond. Adding in the potential upside from Yakult in Japan and the expected news flow, we reiterate our OUTPERFORM recommendation and increase our target price to €10 (from €7.50).
Together with its Q417 results announced last week, 4SC also reported progress with its R&D activities. All three lead assets – resminostat, 4SC-202 and 4SC-208 – remain on course to be developed for specialty dermato-oncological indications. New details include an update on the 4SC-202 development plan and the news that 4SC’s Japanese partner, Yakult Honsha, joined 4SC’s pivotal resminostat study and will enrol patients in Japan. Our valuation is largely unchanged at €349m or €11.4/share (€11.3/share previously).
Over the past several months 4SC has reported progress with both its clinical-stage assets – resminostat and 4SC-202. The pivotal trial with resminostat as a maintenance therapy in advanced CTCL passed the first DSMB review and is on track to report data in H119. The Phase Ib/II study with 4SC-202 for melanoma has been initiated, while another Phase II study with 4SC-202 for GI cancer should start in Q118. 4SC-208 completes the core portfolio and is expected to enter the clinic in early 2019. Our valuation is largely unchanged at €347m or €11.3/share (€344m previously).
4SC announced today that the scheduled Data Safety Monitoring Board ("DSMB") had identified no safety concerns with the on-going RESMAIN pivotal trial Cutaneous TCell Lymphoma ("CTCL") and recommended the study should continue as planned. With top-line data from RESMAIN for resminostat and first interim data from SENSITIZE for 4SC-202 in melanoma expected in H1/2019 and H2/2018 respectively, there is plenty to drive value over the next 6-18 months. We reiterate our OUTPERFORM recommendation and a fair value of €7.50 / share potentially rising to over €10 / share with expected news flow from the pipeline as well as non-core assets over the next 6 to 12 months.
With a pipeline based on sound proof-of-principle, 4SC is building an independent strategy focussed on orphan drugs with best-in-class blockbusters exploited through major partners. The company's lead product resminostat is in a pivotal trial as a much needed maintenance therapy in the orphan CTCL (Cutaneous T-Cell Lymphoma). Class I HDACi (Histone Deacetylase inhibitors) are showing real promise in combination with the new wave of immuno-therapeutics. Entering phase II in combination with an approved checkpoint inhibitor in melanoma, the safety and efficacy of the Class I HDACi 4SC-202 provide the hallmarks of a best-in-class blockbuster as well as providing a snug fit into the company's orphan strategy. We initiate with an OUTPERFORM recommendation and a fair value of €7.50 / share potentially rising to over €10 / share with expected newsflow from the pipeline as well as non-core assets over the next 6 to 12 months.
4SC’s new core strategy revealed earlier this year has focused on dermato-oncological indications, while its assets for other indications are partnered. The sharp focus will allow 4SC to become an expert in the field and to accumulate commercial know-how, as the company intends to market the core assets (resminostat, 4SC-202 and 4SC-208) in orphan indications on its own. A successful fund-raise in July means that the company now has sufficient funds until 2020 and past several important R&D events. We have overhauled our model to reflect 4SC’s new strategy and our new valuation is €344m or €11.2/share.
4SC has announced an updated development programme, to be funded by an equity fund-raising, which we expect in 2017. The proceeds from this will be used to accelerate development of 4SC’s leading drug candidates. This will include continuing to progress resminostat in CTCL (initiated at end 2016), a subsequent filing of a marketing authorisation application in Europe (2019) and progression of resminostat into a further pivotal study in HCC (2018). 4SC also expects a pivotal study in 4SC-202 in Merkel cell carcinoma (2018) and the progression of 4SC-208 into clinical evaluation (early 2019). Our forecasts and valuation are under review. We believe that if 4SC executes the proposed plans it could be a significant and positive step.
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A number of REITs have the ability to thrive in current market conditions and thereafter. Not only do they hold assets that will remain in strong demand, but they have focus and transparency. The leases and underlying rents are structured in a manner to provide long visibility, growth and security. Hardman & Co defined an investment universe of REITs that we considered provided security and “safer harbours”. We introduced this universe with our report published in March 2019: “Secure income” REITs – Safe Harbour Available. Here, we take forward the investment case and story. We point to six REITs, in particular, where we believe the risk/reward is the most attractive.
Companies: AGY ARBB ARIX BUR CMH CLIG DNL HAYD NSF PCA PIN PXC PHP RE/ RECI SCE SHED VTA
Laboratory Services Contracts Signed
Companies: Open Orphan
The announcement announced today highlights the potential breadth of the KidneyIntelX platform, opening up new routes to expand data inputs and test utility, and create opportunities alongside pharmacological therapy as a companion diagnostic. The first agreement with the University of Michigan adds an additional 800 chronic kidney disease (CKD) patients (adding to Mount Sinai’s 1,500 patients and the University of Groningen’s 3,500 patients) to analysis the performance of KidneyIntelX in different settings. This will ultimately carry additional sway with healthcare centres, regulators, and payers. The option to exclusively license a new urinary biomarker, urinary Epithelial Growth Factor (uEGF), shows the potential to add additional biomarkers and body fluids into the platform to further enhance the prognostic performance of KidneyIntelX. We understand there is a relatively immaterial upfront payment to access this new biobank, and a similar immaterial cash payment to gain the biomarker license option with additional milestones and standard tiered royalties payable if exercised. The second data sharing agreement with a major undisclosed pharma partner highlights KidneyIntelX’s potential use as a companion diagnostic (e.g. for SGLT2 inhibitors) and the potential to use the test multiple times to monitor drug response. This builds on work being conducted in Groningen with data expected H2 CY’20. Ultimately, pharmaceutical collaborations could drive additional long-term value creation and may open opportunities for lucrative licensing and M&A deals. At this juncture we make no changes to our forecasts and eagerly await further updates. We reiterate our positive stance on Renalytix.
Companies: Renalytix AI
Today Ergomed held its annual general meeting (AGM). As expected, no new financial details were provided, although the executive chairman released a statement with a general business update. Q120 trading was good with ‘solid overall growth in revenue’ and cash generation ‘remained strong’. In Q220, Ergomed continued to grow the order book across the business and maintained its ‘revenue growth trend’. Its staff successfully adapted to remote working conditions and no employees were made redundant or furloughed. The H120 trading update will be released in July 2020 as usual, but Ergomed stated within its AGM update (June 10) that it is confident the results will be ‘in line with current market expectations’.
Renalytix’s US IPO filing document went live overnight (having previously been filed confidentially). Whilst there are no details on size of offering, but the document is rich with details of the use of proceeds which we encourage UK investors to read. We are doing the same and will update our views in due course. Associated with the US filing document, another release this morning announces the publication of a circular, and outlines details for a new General Meeting on the 13 July 2020 to approve the issue of new shares, as well as board changes if the US IPO goes ahead. Namely, Julian Baines (Non-executive Chair) and Richard Evans (NED and Audit committee Chair) are stepping down from the board, Christopher Mills will assume the role of interim chair whilst a search for a successor is conducted.
Cambridge Cognition ("COG") has provided a trading update for the 6 months to 30 June and presented its growth strategy at an excellent Capital Markets Day. The Group continues to build on an impressive H1 2020, announcing additional contract wins that take the order intake to £4.9m (+88% vs H1 2019). COG is currently 'seeing unprecedented demand' for its solutions which enable pharmaceutical companies to continue clinical trials even while participants are unable to physically visit clinical trial sites.
Companies: Cambridge Cognition
With CHF13bn ($14bn) annual sales, Roche is a dominant force in the global diagnostics market. Interestingly, in recent years, most diagnostics majors have witnessed material re-ratings – also a function of increased M&A euphoria. Now, in the backdrop of COVID-19, Roche has also emerged as a prominent player on the testing front. With big pharmas moving away from (low-growth) non-pharma offerings, is it time for Roche to consider unlocking value from Diagnostics?
Companies: Roche Holding
AVO’s goal is to deliver an affordable and novel proton therapy (PT) system, called LIGHT, based on state-of-the-art technology developed originally at the worldrenowned CERN. Over the past two years, the project has been significantly derisked through important technical milestones. AVO is working on the verification and validation phase, prior to LIGHT being used on the first patients to support CE certification. A recent equity issue, new loan facilities and some commercial announcements earlier in 2020 highlight the increasing confidence that is building in AVO’s ability to achieve its goal to deliver LIGHT in the near future.
Companies: Advanced Oncotherapy
ReNeuron has released further follow-up data from the ongoing human retinal progenitor cell (hRPC) trial, which shows a robust sustained averaged response. This data set completes the six-month data on eight patients and extends, for one individual, to 18 months, who showed a good net gain. The next dose level, two million cells in nine patients, remains delayed due to COVID-19. A filing to start a pivotal study is expected in the second half of CY21. Our indicative value remains at £107m.
Companies: Reneuron Group
Hutchison China MediTech (HCM) is on the brink of global launches of two assets from its internally developed oncology portfolio. In 2022 we expect US launches of surufatinib (broad NET indication) two years earlier than forecast as well as savolitinib (NSCLC). Recently the FDA granted fast-track designation to fruquintinib in mCRC and we forecast global launch in 2023. In China, HCM has laid the foundations to capitalise on the slew of additional novel oncology drugs (expected by end 2021). HCM is well funded (following the recent $100m equity investment from General Atlantic, plus warrants granted for an additional $100m in 18 months) as it accelerates the global development of its unpartnered assets and expands its global commercial outreach. Beyond 2024 we expect sustainable profitability and margin expansion. Our increased valuation is $6.3bn.
Companies: Hutchison China Meditech
Hutchison China MediTech (HCM) is on the brink of global launches of two assets from its internally developed oncology portfolio. In 2022 we expect US launches of surufatinib (broad NET indication) two years earlier than forecast as well as savolitinib (NSCLC). Recently the FDA granted fast-track designation to fruquintinib in mCRC and we forecast global launch in 2023. In China, HCM has laid the foundations to capitalize on the slew of additional novel oncology drugs (expected by end 2021). HCM is well funded (following the recent $100m equity investment from General Atlantic, plus warrants granted for an additional $100m in 18 months) as it accelerates the global development of its unpartnered assets and expands its global commercial outreach. Beyond 2024 we expect sustainable profitability and margin expansion. Our increased valuation is $6.3bn.
We are initiating coverage on specialist pharmaceutical services provider Ergomed. We believe it should prove relatively resilient during the COVID-19 crisis and has the fundamentals in place to execute its growth strategy. Ergomed announced impressive audited numbers for FY19, with revenue up 26% to £68.3m and EBITDA up 5.5x to £12.5m. The FY19 announcement is effectively Ergomed’s fourth profit upgrade for FY19 and a small beat on recently reset FY19 expectations. Ergomed trades at a discounted EV/EBITDA of 10.1x vs the contract research outsourcing (CRO) sector average of 11.5x (FY20). We value Ergomed at £186m or 399p/share. Ergomed’s strong organic growth is benefiting from a clear strategic focus on high growth pharma sectors, margin control and order book growth (up 15% to £125m in FY19, giving 90% visibility to 2020).
A continued strong recovery in the important China and US markets means group revenues are expected to be significantly ahead of expectations. The strong revenue performance and improving gross margins has also delivered EBITDA significantly ahead of consensus expectations. The outlook remains robust, supported by ongoing recovery in China in particular and a strong order book gives good visibility over H1’21 revenues. We prudently leave outer year forecasts unchanged for now, but view the sensitivity as being to the upside, with potentially material medium-longer term upside from the vaccines currently in development (but not in forecasts). On an FY21 multiple of 11.2x EBITDA, the valuation is undemanding.
Companies: Eco Animal Health Group
Diaceutics is launching a cloud based diagnostics commercialisation platform for the precision medicine market that will bring significant functional gains to customers and create meaningful internal efficiencies. The company has raised £20.5m gross in an equity Placing of new ordinary shares to fund the ongoing development of both the business and the new platform.
New York state approval is a pivotal moment for Renalytix. Approval facilitates the launch of KidneyIntelX with launch partner Mount Sinai and progressively derisks the investment hypothesis. Understandably with Mount Sinai in the heart of the NYC Covid-19 health pandemic, testing and first commercial revenues is now set to begin in calendar Q3 2020 (vs Q2 2020) once the integration of KidneyIntelX into the Mount Sinai electronic health record is completed. Renalytix is now licensed to provide KidneyIntelX testing services in 47 states in the US, with the remaining licenses pending in calendar 2020. We have adjusted our forecasts to reflect a full launch in the Mount Sinai system in FY’21 (June yearend) and have upgraded our valuation analysis through unwinding our risk adjustment from 60% to 65%. Our valuation analysis now implies an intrinsic value of 477p/share (previously 459p/share).