Our Holdings

3.6%

Agios Pharmaceuticals

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Agios Pharmaceuticals

3.6%

The two most advanced oncology programs of Agios Pharmaceuticals are targeting mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes, which are implicated in hematologic malignancies and solid tumors. Data with IDH2 inhibitor Idhifa (AG-221) were compelling and due to the high response rate and well-defined group of patients who benefited, the drug was given an accelerated approval in August 2017. We estimate the worldwide market opportunity for Idhifa at USD  750  mn for acute myeloid leukemia (AML). Celgene has worldwide rights to Idhifa, and Agios will receive milestones and an estimated 15% royalty on sales. Data with IDH1 inhibitor AG-120 in AML were also promising and the product was approved in July 2018. Results with AG-120 in rare solid tumors were not as compelling as hoped, and we include little revenue potential from these indications despite continued development. Finally, the company is developing AG-348, a novel compound for the treatment of pyruvate kinase deficiency that reported compelling proof-of-concept data, and Phase III trials are now underway.

1.2%

Akcea Therapeutics

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Akcea Therapeutics

1.2%

Akcea was spun out of Ionis Pharmaceuticals and is developing antisense drugs to treat rare and severe diseases. Its lead product is Tegsedi which was launched in late 2018 for the treatment of hereditary transthyretin amyloidosis, a rare and severe disease. The company received a complete response letter for Waylivra for the treatment of familial chylomicronemia syndrome, a rare lipid disorder, and is pursuing a path forward with the FDA. Akcea also has a pipeline of next generation lipid products based on its LICA technology which allows for much lower dosing and higher potency. ANGPTL3-Lrx is in a Phase I/II study for rare hyperlipidemias and is also being evaluated in fatty liver diseases such as NAFLD and NASH. Akcea has two LICA programs partnered with Novartis for larger diseases, APO(a)-Lrx and APOCIII-Lrx for patients with elevated risk factors for cardiovascular disease. Ionis remains a majority shareholder.

1.6%

Alder Biopharmaceuticals

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Alder Biopharmaceuticals

1.6%

Alder is a clinical-stage company with a differentiated antibody discovery and manu-facturing platform to design and select antibodies that have the potential to maximize efficacy in various therapeutic indications including inflammatory and neurological conditions. Their clinical candidate, eptinezumab, is an antibody that inhibits calcitonin gene-related peptide (CGRP), a well-validated molecular target shown to trigger migraine attacks. Eptinezumab has recently completed Phase III clinical testing for the prevention of both chronic and frequent episodic migraines. Data were highly significant and notable for achieving rapid, robust, and durable efficacy. Alder is the only company with an anti-CGRP therapeutic that could be marketed as a durable, intravenous formulation administered by neurologists in-office – an infusion that could be given every three months, compared to monthly or biweekly self-administered subcutaneous injections at home. The company expects to apply for FDA approval in early 2019.

4.0%

Alexion Pharmaceuticals

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Alexion Pharmaceuticals

4.0%

Alexion is developing drugs for rare disorders. Its lead product Soliris was approved in the US and Europe in 2007 for paroxysmal nocturnal hemoglobinuria (PNH) and we expect sales in PNH to reach about USD 2.0 bn. Atypical hemolytic uremic syndrome (aHUS) is the next indication for which Soliris gained approval in the US and Europe in 2011. We estimate it adds another USD 2.0 bn market opportunity for Soliris. Other indications such as myasthenia gravis and neuromyelitis optica could add an additional USD 1.0 to 2.0 bn in sales. To maintain its dominance, Alexion is in advanced development with a next-generation Soliris, ALXN-1210, which has an improved dosing profile and showed positive Phase III results. To diversify the revenue base away from Soliris, the company received approval of a novel compound for hypophosphatasia, Asfotase Alfa, in March 2015 and sales to date have exceeded expectations. In addition, Alexion gained Kanuma for lysosomal acid lipase (LAL) deficiency via its May 2015 acquisition of Synageva, and while the launch has been slow, the product should eventually be a more meaningful contributor to revenue. In 2018, the company acquired two additional rare disease companies, Wilson Therapeutics and Syntimmune.

4.2%

Alnylam Pharmaceuticals

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Alnylam Pharmaceuticals

4.2%

Alnylam Pharmaceuticals is the market leader in RNA interference (RNAi) therapeutics. This treatment approach selectively blocks the synthesis of specific disease-causing proteins. Their first marketed therapy, Onpattro (patisiran), received approval in 2018 for TTR amyloidosis, a rare and serious disorder in patients diagnosed with familial amyloidotic polyneuropathy (FAP). In addition to Onpattro, Alnylam has a broad pipeline of candidates, including four programs that have advanced to the clinical development stage. These include Fitusiran, which pursues a revolutionary approach in the treatment of hemophilia and rare bleeding disorders, Givosiran for the treatment of acute hepatic porphyrias, and Lumisiran, which received breakthrough status for primary hyperoxaluria. Alnylam continues to support its collaboration with The Medicines Company in their advancement of inclisiran into Phase III studies, which investigates RNAi disruption of PCSK9 for the treatment of hypercholesterolemia. Data thus far have been supportive of a once-quarterly and possibly biannual subcutaneous administration, which has obvious advantages over other PCSK9 antibody therapies.

3.4%

Argenx

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Argenx

3.4%

Argenx is a Belgian clinical stage small cap biotechnology company developing targeted antibody therapies through its multiple antibody platforms. The company has a variety of mid-to-late stage clinical drug candidates with ARGX-113 (efgartigimod) being the lead asset. This molecule has proven to be efficacious in Phase II proof of concept in two IgG-mediated autoimmune diseases (myasthenia gravis and ITP) with two other indications (pemphigus vulgaris and CIDP) being currently evaluated. Important clinical trial read-outs from this program are expected in the coming 12 to 18 months. A solid balance sheet and experienced management rounds the company’s profile. Argenx can be considered an antibody platform company targeting novel scientific pathways in indications with high unmet medical need with little competition and innovation in the last decades.

0.5%

Arvinas

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Arvinas

0.5%

Arvinas is the leader in the development of novel small molecules designed to facilitate targeted protein degradation. The company's pipeline relies on the PROTACs (PROtein TArgeting Chimera) technology, trying to harness the cell's natural "garbage disposal" system for damaged/unneeded proteins and redirecting it to specifically degrade a target protein. ARV-110, Arvinas’s lead product candidate, is an oral PROTAC that degrades the androgen receptor to treat castration-resistant prostate cancer (CRPC). An open-label Phase I dose-escalation study enrolling up to 36 men with mCRPC who previously received 2nd-gen endocrine therapy (Zytiga/Xtandi) is ongoing with preliminary efficacy results awaited in H1-20. The second clinical asset of the company, ARV-471 is an oral PROTAC targeting the estrogen receptor (ER) protein, for the treatment of metastatic ER positive / HER2 negative breast cancer. The start of Phase I dose-escalation trial in patients has occurred in Q3-19, with results awaited during 2020. Despite the early stage of development, Arvinas has already 3 partnerships in place. In 2015, Genentech signed a collaboration to develop an undisclosed number of PROTACs for up to USD 650 mn. In January 2018, Arvinas partnered with Pfizer for up to USD 830 mn and in June 2019, Bayer signed a collaboration for up to USD 685 mn in pharma and crop science space.

1.2%

Audentes

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Audentes

1.2%

Audentes is a clinical stage gene therapy company focused on rare diseases. The company has two clinical stage programs and importantly, commercial scale, in-house manufacturing capability that is GMP-approved. AT132 is the lead product in Phase I/II for the treatment of X-linked myotubular myopathy (XLMTM). The second clinical compound is AT342 in Phase I/II for the treatment of Crigler-Najjar syndrome (CN), but the drug needs to be dosed higher as the first patient data at the lowest dose saw a return to baseline following a reduction in the target. Beyond the two lead assets, there are two preclinical compounds and a yet to be named compound. Given the data seen so far with the lead asset, the company will discuss the regulatory path with the FDA and present the data, which we believe have established proof of concept thus far, with durability being the main question. The manufacturing facility has 2 500 liters bioreactors with additional capacity of up to 5 000 liters. The same process, facility, and scale have been used from the beginning which is a very important factor in the regulatory process. The manufacturing process uses a mammalian, serum-free suspension culture which allows for increased scalability versus adherent cultures.

3.3%

Celgene

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Celgene

3.3%

Celgene specializes in oncology and inflammatory diseases and has very strong fundamentals and positive long-term prospects based on products such as Revlimid, Pomalyst, Otezla and its robust pipeline of early-stage products. We expect Revlimid US revenue to continue to grow until loss of exclusivity in the 2024/25 timeframe, driven by the combined effects of increased prevalence, penetration and duration of treatment. The company’s acquisition of Receptos broadened their immunology and inflammation franchise beyond Otezla by gaining access to ozanimod, which we expect to be approved in multiple sclerosis late this year and continues to be developed for inflammatory bowel disease (IBD). Celgene’s acquisition of Juno in 2018 as well as their strategic collaboration with Bluebird has established the company as a leader in the CAR-T space. In January of 2019, Bristol-Myers Squibb entered into a definitive merger agreement to acquire Celgene in a cash and stock transaction with an equity value of approximately USD 74 bn. The deal is expected to close in the third quarter of 2019.

0.1%

Cidara Therapeutics

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Cidara Therapeutics

0.1%

Cidara is a biotechnology company focused on treating severe and resistant microbial infections. Its lead product, Rezafungin (in a Phase III study for candidemia and invasive candidiasis), is from the echinocandin class of antifungals but is dosed as a once-weekly infusion, versus daily for the current echinocandins. This would provide the option of treating patients with the best antifungal on an outpatient basis, thus offering significant advantages to both patients and the healthcare system. Initial Phase II data have demonstrated a strong safety profile and confirmed the once-weekly dosing potential along with a favorable efficacy profile. Data from an extension of the Phase II study will read out in 2019. Following a constructive meeting with the FDA, a smaller than expected Phase III study was possible allowing Cidara to also conduct a prophylaxis study in bone marrow transplant patients. Finally, Cidara is the only company developing an immunotherapy platform for serious infections.

1.0%

Crispr Therapeutics

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Crispr Therapeutics

1.0%

Crispr Therapeutics AG is a company with the main part of its operations in Boston, MA. The Company focuses on the development of transformative gene-based medicines for serious diseases using its Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene-editing platform. CRISPR/Cas9 can be programmed to cut, edit and correct disease-associated deoxyribonucleic acid (DNA) in a patient’s cell. The location at which the Cas9 molecular scissors cut the DNA to be edited is specified by guide ribonucleic acid (RNA), which is comprised of a crRNA component and a tracrRNA component, either individually or combined together as a single guide RNA. The Company has business operations in London, the United Kingdom, as well as research and development operations in Cambridge, the United States. Among the CRISPR companies, CRISPR Therapeutics is unique in being the first having entered the clinic (in late 2018) and specifically focussing on ex vivo applications. CTX-001 is in the clinic in Europe for Transfusion-dependent Beta-thalassemia and in the US for Sickle Cell Disease (profit sharing for both programs with VRTX). CRISPR Therapeutics is the only gene editing company having retained full rights for its allogenic CAR-T programs, they are specifically pursuing CD19, BCMA and CD70 as initial targets and entering the clinic in early 2019. Further it has structure a JV with Bayer named Casebia that concentrates on in vivo applications ($300mn deployed by Bayer) as well as a regenerative medicines pact with Viacyte to de-immunize its synthetic pancreas device with gene editing technology.

4.1%

Esperion Therapeutics

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Esperion Therapeutics

4.1%

Esperion Therapeutics is focused on the development of treatments for cardio-metabolic diseases. Bempedoic acid is the only clinical asset and has now completed its registrational Phase III program. ETC-1002’s main target ATP citrate lyase is located upstream of where statins work and ultimately reduces LDL cholesterol by upregulation of the LDL receptor. Bempedoic acid has shown LDL cholesterol reduction levels of around 20% on top of statins, up to 30% as monotherapy and up to 50% in combination with ezetimibe. In contrast to the recently approved subcutaneously administered PCSK9 antibodies, bempedoic acid poses a convenient and more economic once-daily oral solution. In parallel Esperion will submit an NDA for a fixed-dose combination with ezetimibe. Primary markets for both the mono- as well as fixed dosed combination therapy will be the statin-intolerant population as well as additional treatment for patients whose LDL cholesterol levels are not sufficiently controlled with a maximum tolerated statin. Regulatory submission in the US and in Europe are ex-pected in the first and second quarter 2019.

1.6%

Exelixis

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Exelixis

1.6%

Exelixis is a biotechnology company focused on oncology. The company has one of the most potent tyrosine kinase inhibitors (TKI) on the market. Cabozantinib is approved for the treatment of all stages of renal cell carcinoma (RCC; kidney cancer). Additionally, a Phase III study in second-line hepatocellular carcinoma (HCC; liver cancer) was stopped early due to a positive survival benefit, and we expect this new indication to add incremental value to the cabozantinib franchise. Cabozantinib is also approved for medullary thyroid cancer. Importantly, the drug is being tested in various tumor settings with immune-oncology agents, which can add further, substantial value. Exelixis partnered a second TKI, cobimetinib, with Roche and is approved for the treatment of metastatic melanoma. Finally, having reached profitability, Exelixis is now at a point where it can invest more aggressively in its internal pipeline, which should create value in the future.

0.5%

G1 Therapeutics

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G1 Therapeutics

0.5%

G1 Therapeutics is a clinical-stage small cap biotechnology company focused on the discovery and development of cancer treatment therapeutics. The company has two distinct clinical-stage selective inhibitors of cyclin-dependent kinases 4/6 (CDK4/6i) in its pipeline, trilaciclib and G1T38, both being evaluated in combination with multiple regimens. Whereas trilaciclib could become the first CDKi to be used as a myelosparing agent, the second asset, G1T38, is a fast follower and is currently being evaluated in yet untapped indications by the other CDKi already on the market. The strong scientific rationale coupled with the available clinical data and the proven mode of action gives us confidence that the upcoming multiple readouts in several indications over the coming twelve months for both assets will confirm their clinical profile.

0.9%

Gilead

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Gilead

0.9%

Gilead develops drugs primarily for infectious diseases such as HIV and hepatitis, as well as cancer. The first product, Viread, was launched in 2001 and is a key component in treatment regimens for HIV. Most recently, it launched regimens that include a replacement for Viread with a better long-term safety profile, which should enable it to maintain its leadership when Viread goes generic. The introductions of Hepsera and Viread established Gilead as an important player in the treatment of hepatitis B infection. Gilead’s acquisition of Pharmasset enabled it to become the market leader in the USD 20+ bn hepatitis C (HCV) space. Indeed, peak sales in 2016 of its lead products, Sovaldi and Harvoni, were followed by a precipitous decline, and we expect a continued decline in future years due primarily to pricing and competition. To offset the declining HCV sales, the company purchased Kite Pharmaceuticals, a leader in CAR-T therapy, in October 2017. The first product, Yescarta, was approved in October 2017 for diffuse large B-cell lymphoma (DLBCL) and we expect label expansions for other hematologic indications to follow. Meanwhile, Phase III data on development candidates for rheumatoid arthritis and NASH are expected in 2019.

3.8%

Halozyme Therapeutics

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Halozyme Therapeutics

3.8%

Halozyme Therapeutics is a biopharmaceutical company with a business model consisting of two platforms. Enhanze is based on partnerships with pharmaceutical companies that use Halozyme’s rHuPH20 to prepare subcutaneous formulations of intravenous therapies. The company receives upfront milestone payments as well as a steady flow of royalties. Partnered products include blockbusters such as Herceptin and Rituxan as well as future products such as Darzalex, Opdivo or AXLN-1210. The second platform is based on PegPH20, which is being tested for the treatment of pancreatic cancer in combination with chemotherapy and in many other cancers in combination with Roche’s anti-PD-L1 Tecentriq. A Phase III study in pancreatic cancer has almost completed enrollment and is expected to read out on the Overall Survival (OS) endpoint by year-end 2019.

0.9%

Homology Medicines

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Homology Medicines

0.9%

Homology Medicine is a genetic medicines company with a proprietary platform based on AAV vectors derived from human CD34+ cells, known as AAVHSCs (FIXX has 15 different capsids). Sequence analysis has mapped AAVHSCs to Clade F, which also has AAV9 as one of its members. The company is building both a gene therapy and gene editing pipeline based on this technology which they licensed from City of Hope. It is believed that the vectors will be less immunogenic, have natural tropism for desired human tissues, and increased efficiency for homologous recombination. Its lead program is HMI-102 which is an AAVHSC8 vector containing the human phenylalanine hydroxylase (PAH) gene and a liver specific promoter being developed for classic Phenylketonuria (PKU) patients (Phe > 1,200 µmol/L). PKU is an inborn error of metabolism where there are mutations in the PAH gene resulting in the inability to metabolize Phe, which can result in severe neurological impairment. Preclinical models in the established and commercially validated ENU2 mouse model have generated encouraging data leading the company to start a Ph I/II proof-of-concept study in 2019 with inital proof of concept data by year-end 2019. The first gene editing program HMI-103 leverages the same delivery vehicle (AAVHSC) as its gene therapy relative HMI-102, but excludes a promotor and flanks the transgene with two homology arms to drive integration of the transgene into a specified region by homologous recombination. This poses an inherent safety advantage in comparison to other gene editing technology that have to create single- or doubles strand-breaks in the patient DNA by cutting with an endonuclease (Cas9 or Fok-I), which mainly trigger error-prone no-homologues end joining (NHEJ) for repair as well as have higher associated risks of off-target cutting and on-target effects (large genomic rearrangements or deletions). The drawback is lower editing efficiency due to lack of endonuclease cutting.

8.2%

Incyte

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Incyte

8.2%

Incyte is focused on hematologic disorders, inflammatory disorders, and cancer. Their marketed product is Jakafi, an oral JAK-2 inhibitor that received approval for myelofi-brosis (MF) and polycythemia vera (PV) in 2011 and 2014, respectively. We estimate that MF and PV represent a USD 3+ bn market opportunity in the US and Europe. Phase III trials in graft-versus-host-disease (GvHD) are also ongoing and could add another USD 500+ mn in sales if approved in 2019. In November 2009, Novartis licensed ex-US rights to Jakafi. A second-generation JAK-2 inhibitor, Baracitinib, posted positive data from several Phase III trials in rheumatoid arthritis and the product was launched as Olumiant in 2018. Incyte will receive royalties from partner Eli Lilly. Progress on other cancer compounds in its pipeline, including an FGFR inhibitor for cholangiocarcinoma and bladder cancer and a c-Met inhibitor for lung cancer, continues.

1.4%

Intercept Pharmaceuticals

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Intercept Pharmaceuticals

1.4%

Intercept Pharmaceuticals is focused on the development of bile acid analogs for the treatment of cholestatic liver diseases. This disease area primarily includes highly prevalent non-alcoholic steatohepatitis (NASH) as well as the orphan diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Intercept’s lead product is Ocaliva, a first-in-class farnesoid X receptor (FXR) agonist, was approved in the US and Europe for PBC in 2016. As a second and commercially far more attractive indication, Intercept also started a pivotal trial for NASH that is expected to read out in the first half-year 2019. NASH, being an obesity and metabolic syndrome-linked disease, has the potential to take on epidemic proportions in western and emerging societies over the coming years. It is projected to be the leading cause of costly liver transplants and liver cancer by 2020. With currently no drug approved, there clearly is an unmet medical and health economic need for new treatments. Intercept’s Ocaliva is the drug furthest in development for NASH and the first to show an anti-fibrotic effect on liver histology.

0.6%

Intra-Cellular Therapies

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Intra-Cellular Therapies

0.6%

Intra-Cellular Therapies is a biopharmaceutical company developing treatments for disorders that affect the central nervous system. Their wholly owned lead product candidate is Lumateperone, a 5-HT2A serotonin receptor antagonist that also modulates dopamine and serotonin transporters, which was filed for FDA approval in late 2018 for the treatment of schizophrenia. Lumateperone could prove highly differentiated from other anti-psychotics due to its ability to modulate multiple neurotransmitter pathways simultaneously. This was demonstrated in their first pivotal Phase III trial which showed strong efficacy and placebo-like safety. Tolerability and compliance on current schizophrenia therapies is challenging due to a range of motor and metabolic side effects, which is where Lumateperone has proven to be differentiated. Intra-Cellular is also evaluating Lumateperone in two Phase III trials for the treatment of bipolar depression to be completed in 2019. The company also has a PDE-1 inhibitor, ITI-214, in Phase II trials evaluating its role in Parkinson’s disease and other indications.

14.8%

Ionis Pharmaceuticals

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Ionis Pharmaceuticals

14.8%

Ionis Pharmaceuticals is the leader in the space of antisense, with over 40 compounds in development using this technology. Antisense allows for the control of protein production at the genetic level. Our focus and investment strategy revolve around the technology platform, which has demonstrated significant progress. Spinraza (partnered with Biogen) was approved in late 2016 following two positive Phase III studies in spinal muscular atrophy, and had a very strong launch throughout 2017 and 2018. Tegsedi, partnered with Akcea, for hereditary transthyretin amyloidosis polyneuropathy, was approved in the US and EU in 2018. Our focus going forward is on the company’s next-generation technologies such as 2.5 and LICA. Thus, Ionis remains an important and truly innovative investment in our portfolio.

0.3%

Kezar Life Sciences

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Kezar Life Sciences

0.3%

Kezar Life Sciences is a development-stage biotechnology company focused on developing novel small molecule therapeutics targeting immunoproteasome inhibition for the treatment of autoimmune disorders. KZR-616, Kezar’s lead product candidate, is currently in Phase Ib dose escalation in patients with systemic lupus erythematosus (SLE) with or without active nephritis. Following the conclusion of this trial in H1 2019, the company plans to start four Phase II trials in autoimmune disorders with high unmet medical need where proteasome inhibitors like Velcade have proven efficacious but too toxic for chronic treatment.

1.6%

Macrogenics

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Macrogenics

1.6%

Macrogenics has multiple compounds in clinical development that were generated using its propriety Fc-optimization technology that simultaneously reduces resp. enhances binding to inhibitory resp. activating FcyRs, thus dramatically increasing antibody-dependent cellular cytotoxicity (ADCC), and its DART (dual-affinity re-targeting) platform. The company believes its DART platform has overcome the challenges of construct instability and short half-lives encountered by other dual-specific antibodies by incorporating proprietary covalent disulfide linkages and particular amino acid sequences that efficiently pair the chains of the DART molecule. This results in a structure with enhanced manufacturability, long-term structural stability, and the ability to tailor the half-lives of the DARTs to their clinical needs. Data from clinical trials with multiple products are expected throughout 2019.

2.4%

Moderna

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Moderna

2.4%

Moderna Therapeutics is pioneering a new class of medicine made of messenger RNA. Moderna recently gathered a lot of attention through the record-breaking IPO, which raised over USD 600 mn in December 2018. A substantial amount of the USD 3 bn of total capital raised since inception in 2011 has been invested in what is now the leading mRNA technology platform in order to be able to quickly drive development candidates into the clinic on a broad front of therapeutic and prophylactic applications. Their pipeline now includes 21 development candidates, with 10 of them in the clinic, for mRNA-based vaccines as well as treatments in diverse therapeutic areas. In our view, the key programs that will be reading out clinical data within the next few years include the rare liver disease MMA and PPA, the proprietary vaccines in congenital CMV and hMPV+PIV3, the intra-tumorally injected cytokine cocktail OX40L+IL23+IL36 gamma, the personalized cancer vaccine and early data on the VEGF Phase II during CABG-surgery.

0.8%

Myovant Sciences

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Myovant Sciences

0.8%

Myovant is a biopharmaceutical company with a focus on endocrinology in women’s and men’s health. Its lead candidate, Relugolix, is an oral GnRH antagonist in Phase III development for three indications, endometriosis, uterine fibroids, and advanced prostate cancer. Endometriosis is a condition where part of the endometrium grows outside of the uterus leading to severe pain, painful intercourse, and bleeding. Uterine fibroids is a condition that can lead to painful menstruation and excessive bleeding, and potentially surgical removal of the uterus. Advanced prostate cancer is cancer of the prostate that continues to grow despite castration and/or radiation. Partner Takeda announced positive data from two Phase III trials in uterine fibroids in Japanese women, further validating Relugolix’s mechanism of action. We expect data from all three Phase III trials in the US in 2019. Myovant owns worldwide rights outside of Asia.

2.0%

Myokardia

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Myokardia

2.0%

Myokardia is one of only a few small biotech companies in the cardiovascular disease area. The company’s initial focus is on the treatment of inheritable cardiomyopathies, a group of rare, genetically driven forms of heart failure that result from biomechanical defects in cardiac muscle contraction. The most advanced pipeline asset is MYK-461 (mavacamtem), an allosteric inhibitor of cardiac beta myosin function that is being investigated in obstructive hypertrophic cardiomyopathy (oHCM or HoCM). The company posted intriguing Phase II results not only showing direct improvement in biomarkers (up to 15% reduction in ejection fraction, up to 90% reduction in LVOT gradient) but also an increase of up to 17% in exercise capacity and an improvement in symptoms (1 Class NYHA improvement on average). A single Phase III trial aiming at exercise capacity and symptom improvement has been initiated with an expected readout in 2020. Further studies include a Phase II study in non-obstructive HCM as well as early dose escalation data in H2-18 for their second asset (MYK-491) that is being developed for DCM (dilated cardiomyopathy).

1.4%

Nektar Therapeutics

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Nektar Therapeutics

1.4%

Nektar Therapeutics is focused on developing novel drugs for oncology, autoimmune disease, and chronic pain. The most important product in the pipeline is NKTR-214, a CD122-biased agonist designed to achieve broader efficacy, better safety, and an improved dosing schedule than IL-2 with its prodrug design and sustained signaling. Initial results from the dose-escalation portion of the Phase I/II trial with NKTR-214 plus PD1 inhibitor Opdivo, as well as data from an extension cohort of melanoma patients, showed evidence of activity and a favorable safety profile. Specifically, there was a 53% overall response rate and a 24% complete response rate in first-line melanoma patients who received the combination. Encouraging results were also shown in kidney, lung, and bladder cancer, and data from larger cohorts of patients with these tumor types are due in 2019. Meanwhile, a large pivotal program targeting these tumors, as well as others, is underway with partner Bristol-Myers. Terms of the partnership include total upfront payments of USD 1.85 bn, USD 1.8 bn in potential milestones, and a cost and profit sharing agreement.

9.0%

Neurocrine Biosciences

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Neurocrine Biosciences

9.0%

Neurocrine is a biopharmaceutical company with a focus on women’s health and CNS disorders. Neurocrine received approval for Ingrezza (Valbenazine) for tardive dyskinesia in mid-2017 and launched the product in the US with continued growth driven by underlying patient and physician demand. Tardive dyskinesia is a condition where patients have involuntary movements that cannot be controlled. Its second product is Elagolix, which is an oral GnRH antagonist approved for endometriosis and uterine fibroids. Endometriosis is a condition where part of the endometrium grows outside of the uterus leading to severe pain, painful intercourse, and bleeding. Uterine fibroids is a condition that can lead to painful menstruation and excessive bleeding, and potentially surgical removal of the uterus. Partner AbbVie will file for approval in uterine fibroids in 2019.

5.4%

Radius Health

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Radius Health

5.4%

Radius Health is a company focused on women’s health and oncology. The company currently markets Tymlos (abaloparatide), a synthetic human PTHrP analogue. Tymlos’ faster onset of action and reduction in fractures in nonvertebral sites like the hip and wrist versus Eli Lilly’s Forteo are differentiating and should allow it to capture significant market share. Radius received approval in 2017, and we expect 2019 to be a year of continued Tymlos growth and reimbursement as well as pipeline execution. Importantly, Radius is developing a transdermal patch formulation which could greatly enhance the outcomes in women with osteoporosis. Transdermal data presented to date has shown a meaningful improvement in its profile, and we expect a pivotal study to begin in mid-2019. Furthermore, the company has elacestrant, a selective estrogen receptor degrader (SERD), in Phase III development for estrogen-receptor-positive breast cancer. Elacestrant diversifies Radius’ portfolio and strengthens its focus on women’s health.

5.6%

Sage Therapeutics

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Sage Therapeutics

5.6%

Sage Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for CNS disorders utilizing their GABA-A receptor-targeted proprietary platform. The company’s lead therapy, Zulresso (brexanolone), is expected to be approved in March 2019 as an intravenous treatment for post-partum depression (PPD). Zulresso has shown rapid and durable efficacy, which sets it apart from all classes of drugs currently used in the field of depression and mood disorders. Sage is also developing an oral, follow-on version of Zulresso, called SAGE-217, which recently delivered positive Phase III data in PPD, and further supported by a successful Phase II study in major depressive disorder (MDD). An ongoing Phase III trial in MDD is expected to read out in 2020, after which the company plans to file a complete application for approval in both PPD and MDD. Sage is also investigating SAGE-217 in essential tremor and Parkinson’s disease and owns an NMDA program with SAGE- 718, targeting several orphan neurological indications.

1.0%

Sangamo Therapeutics

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Sangamo Therapeutics

1.0%

Sangamo Therapeutics is uniquely positioned as the dominant and almost exclusive holder and developer of Zinc-finger-based genomic editing (ZFN) IP. One of the key achievements of the new CEO on the pharmacological side was the manifold improvement in selectivity of the ZFN platform (100x), thereby pushing off-target cutting below the limit of detectability, which enables the company to conduct the first in vivo gene-editing clinical trial (MPS II). Further the company now also pursues classic gene therapy approaches through the formulation expertise (that they gained while delivering ZFN) and IP around AAV2/6 (AAV6 capsid with AAV2 promotor/genome), e.g. in haemophilia A (Phase I/II running) as well as Fabry’s disease (IND). It will be key for Sangamo to successfully develop their ZFN platform for their first proprietary projects (MPS I, MPS II, hemophilia B) and based thereon deploy that or newer generations of ZFN into further liver albumin locus targeting applications, while reaping the optionality from partnered projects (hemophilia A with Pfizer, ex vivo collaborations with Bioverativ and Kite, gene regulation ZFP without nucleases with Shire and Pfizer).

0.6%

Scholar Rock

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Scholar Rock

0.6%

Scholar Rock is a biotech company with a platform based on the understanding of the extracellular activation of growth factors. By targeting the pro and latent forms of the growth factors with antibodies, not the active/mature factor (given the very high degree of similarity in amino acid sequences in the active sites across the TGF-beta superfamily), the company believes it can avoid the off-target toxicities that have plagued this field historically. Its lead compound is SRK-015, a monoclonal antibody targeting pro myostatin and latent myostatin, is designed to inhibit the activation of myostatin thereby promoting muscle growth and function. The initial indication is later onset spinal muscular atrophy (Type 2 and 3) where it can potentially be used in combination with Spinraza and other therapeutics as its mechanism is complimentary, not competitive. Phase II, interim proof-of-concept data are expected in the second half-year 2019. SRRK also plans on announcing a second muscle wasting indication in 2019. The platform technology is also focused on TGF-beta 1 in the IO space as well as fibrosis. The fibrosis indications have been partnered with Gilead.

6.7%

Vertex Pharmaceuticals

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Vertex Pharmaceuticals

6.7%

Vertex’s core focus is cystic fibrosis. CFTR potentiator Kalydeco was launched in the US and Europe in 2012 for a subgroup of patients with cystic fibrosis. While the initial market opportunity is limited to around 5% of the patient population, we believe that sales could reach USD 1.0 bn with the inclusion of other small patient populations on the label. Positive Phase III results with the combination of Kalydeco and CFTR correc-tor VX-809, released in June 2014, enabled Vertex to begin to target the roughly 45% of patients who are homozygous for the most common mutation in the US and Europe in 2015. With this label inclusion, we expect sales of Kalydeco and the Kalydeco/VX-809 combination to reach approximately USD 4.0 bn. The company is also developing correctors that can be combined with Kalydeco and VX-661 to target the remaining patients who are heterozygous for the mutation. Data from Phase III trials announced in november were highly positive and we expect approval to follow in 2019.

1.4%

Voyager Therapeutics

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Voyager Therapeutics

1.4%

Voyager is a clinical-stage biotech company focused on developing novel genetically targeted therapies to treat CNS diseases. The company’s lead asset, VY-AADC, is an AAV-based gene therapy with the objective of increasing the expression of the enzyme responsible for converting levodopa to dopamine (AADC, L-amino acid decarboxylase) in the brains of Parkinson’s disease patients. VY-AADC is currently enrolling patients in a Phase II trial, which will serve as the first of two sham-controlled studies for registration. A Phase III study to begin in 2020 will serve as the second pivotal trial. The company is also developing other AAV vectors targeted at increasing expression of a key gene in Friedreich’s ataxia, delivering monoclonal antibodies, or silencing/knocking down genes using microRNA delivery in diseases like monogenic SOD1 familial ALS and Huntington’s disease. Voyager’s discovery engine has generated programs in five CNS indications, and in the next 18 to 24 months, they plan to initiate at least three other clinical programs.

1.0%

Wave Life Sciences

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Wave Life Sciences

1.0%

Wave is a leader in the space of stereochemistry, with an initial focus on antisense oligonucleotides (ASOs) and exon skipping. In simple terms, stereochemistry refers to the three-dimensional structure of a molecule and how this affects its chemical properties. Current ASOs can contain hundreds to hundreds of thousands of various enantiomers (stereomixture), many of which do not contribute to efficacy, but could be causing toxicity. Wave is able to specifically design their individual molecules (stereo-pure) to contain the desired properties, thus potentially enhancing potency and minimizing toxicity. The company’s lead product is in Phase I/II development for Huntington’s disease and targets very specific point mutations in order to knock down the mutant protein. We expect data in early 2019. Wave’s second program recently entered Phase I development for Duchenne muscular dystrophy (DMD) and acts by skipping exon 51.

All comments as at December 31, 2018 or beginning of investment.

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Media releases / 18.10.2019

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