Our Holdings

5.3%

Agios Pharmaceuticals

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Agios Pharmaceuticals

5.3%

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). Bristol-Myers/Celgene has worldwide rights to  Idhifa, and Agios will receive milestones and an estimated 15% royalty on sales. Data with IDH1 inhibitor Tibsovo (AG-120) in AML were also promising and the product was approved in July 2018. Results with Tibsovo in a rare solid tumor called cholangio-carcinoma were positive and approval for this indication should be granted by the end of 2020. Meanwhile, development of Tibsovo for low-grade glioma continues. 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 should yield data in 2020.

0.2%

Akcea Therapeutics

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Akcea Therapeutics

0.2%

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, partnered with Pfizer, is in a Phase II study for hypertriglyceridemia and is also being evaluated in fatty liver diseases such as NAFLD. Akcea has two LICA programs, one is partnered with Novartis for larger cardiovascular diseases, APO(a)-Lrx. The other is wholly owned by Akcea, APOCIII-Lrx for patients with elevated risk factors for cardiovascular disease. Ionis remains a majority shareholder of Akcea.

3.6%

Alexion Pharmaceuticals

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Alexion Pharmaceuticals

3.6%

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 developing a next-generation Soliris, Ultomiris (ALXN-1210), which has an improved dosing profile and is now approved for PNH and aHUS, with additional indications expected to follow. To diversify the revenue base away from Soliris, the company received approval of a novel compound for hypophosphatasia, Asfotase Alfa, in March 2015 and the product has become a meaningful contributor to revenue. In addition, Alexion gained Kanuma for lysosomal acid lipase (LAL) deficiency via its May 2015 acquisition of Syn-ageva. Continuing its aggressive business development efforts, the company acquired Achillion and formed collaborations with Eidos and Stealth in 2019, adding to the 2018 acquisitions of Wilson Therapeutics and Syntimmune.

4.7%

Alnylam Pharmaceuticals

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Alnylam Pharmaceuticals

4.7%

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 hATTR amyloidosis with polyneuropathy. Another recent RNAi approval came in 2019 with Givlaari (givosiran) for the treatment of acute hepatic porphyrias.  Alnylam has a broad pipeline of candidates, including four programs that have advanced to the late clinical or registrational development stage. These include fitusiran, which pursues a revolutionary approach in the treatment of hemophilia and rare bleeding disorders, lumasiran, which received breakthrough status for primary hyperoxaluria, and vutrisiran, a subcutaneously administered RNAi treatment for  hATTR amyloidosis utilizing their enhanced stabilization chemistry (ESC) GalNAc delivery system. Alnylam continues to support its collaboration with The Medicines Company (recently acquired by Novartis) in their advancement of inclisiran, which investigates RNAi disruption of PCSK9 for the treatment of hypercholesterolemia and offering unprecedented convenience over other PCSK9 antibody therapies.

5.2%

Argenx

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Argenx

5.2%

Argenx is a Belgian clinical stage small cap biotechnology company developing targeted antibody therapies through its multiple antibody platforms. The company’s lead asset, ARGX-113, has proven to be efficacious in proof of concept clinical study in two IgG-mediated autoimmune diseases such as myasthenia gravis and ITP. The company has been pursuing an aggressive clinical development with four clinical trials readout over the next 18 months. Most awaited news flow is the Phase III readout in MG patients awaited for the second half of 2020. 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 moderate competition and innovation in the last decades.

1.3%

Arvinas

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Arvinas

1.3%

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 is ongoing with preliminary efficacy results awaited in the first half of 2020. 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 the third quarter of 2019, with results awaited during 2020. Despite the early stage of development, Arvinas has already three 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.

1.5%

Black Diamond Therapeutics

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Black Diamond Therapeutics

1.5%

Black Diamond Therapeutics is a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies. Black Diamond targets undrugged mutations in patients with genetically defined cancers that currently do not have any effective targeted treatment options. The foundation of the company is built upon a deep understanding of cancer genetics, protein structure and function as well as medicinal chemistry. The Company’s proprietary technology platform, Mutation-Allostery-Pharmacology (MAP), is designed to allow the company to analyze population-level genetic sequencing data to identify oncogenic mutations that promote cancer across tumor types, group these mutations into families having similar protein structures and develop a single small molecule therapy in a tumor-agnostic manner that targets the specific family of mutations. The cornerstone of their approach derives from evolving trends in targeted oncology therapies. Genetic sequencing of cancers has become increasingly widespread, leading to the discovery of multiple genetic alterations which were previously unaddressed, unsuccessfully targeted or overlooked. Today, new baskets of undrugged oncogenic targets have been identified, revealing a significant unmet medical need for novel targeted therapies. The approach offers a substantial opportunity to expand the number of cancer patients who could benefit from precision oncology medicines. The lead candidate BDTX-189 was designed to block the function of an undrugged oncogenic mutations within the HER protein family, which occur across a range of tumor types. Black Diamond submitted an IND (Investigational New Drug Application) for BDTX-189, which was allowed by the FDA in December 2019. The company intends to initiate a Phase 1/2 clinical trial with first patient in Q120 to pursue a tumor-agnostic development strategy.

0.3%

Cidara Therapeutics

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Cidara Therapeutics

0.3%

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. 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. The Phase III IC and candidemia study started in September 2018 with data expected in 2020. The company partnered with Mundipharma for all markets outside the US and Japan, which resulted in near-term funding for the Phase III program. Finally, Cidara is the only company developing an immunotherapy platform for serious infections with influenza as the first target.

1.5%

Crispr Therapeutics

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Crispr Therapeutics

1.5%

Crispr Therapeutics AG is a company with the main part of its operations in Boston, MA. The company focuses on the development of transformative genetic medicines for serious diseases using its Clustered Regularly Interspaced Short Palindromic Re-peats (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. Among the CRISPR companies, Crispr Therapeutics is unique in being the first to have entered the clinic (in late 2018), initially focusing 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 Vertex), promising data from first patients showing successful editing, engraftment and clinical improvement have been presented. Crispr Therapeutics has retained full rights for its allogenic CAR-T programs, they are specifically pursuing CD19, BCMA and CD70 as initial targets and have entered the clinic in late 2019. Crispr further pursues in vivo programs in partnership with Vertex (DMD, DM-1, CF), on its own through the former Bayer joint venture named Casebia as well as a regenerative medicines pact with Viacyte to de-immunize a syn-thetic pancreas device with gene editing technology.

4.8%

Esperion Therapeutics

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Esperion Therapeutics

4.8%

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.  The drug has shown LDL cholesterol reduction levels of around 17 – 18% on top of treatment with statins, around 25% as monotherapy and 35 – 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 approval in the US and in Europe are expected in the first and the second quarter of 2020. Esperion is adequately financed to launch the drugs by themselves in the US, in Europe partner Daiichi Sankyo will be responsible (USD 300 mn upfront, additional milestones and royalties for Esperion).

1.7%

Exelixis

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Exelixis

1.7%

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 was added to the label in January 2019. 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 that 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.

1.6%

Fate Therapeutics

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Fate Therapeutics

1.6%

Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of next-generation cellular immunotherapies for cancer and immune disorders. Their first-in-class cell therapy product candidates undergoing clinical development today utilize healthy donor cells, which are modified ex vivo using pharmacologic modulators, such as small molecules, to improve the cells’ biological properties and therapeutic function. Fate is also pioneering a revolutionary approach to cell therapy – they use renewable master induced pluripotent stem cell (iPSC) lines generated from the proprietary iPSC platform to derive cell therapy product candidates that can be delivered off-the-shelf for the treatment of a large number of patients. Such therapies could overcome the limitations of currently marketed autologous cellular therapies, including cumbersome manufacturing and administration costs. The iPSC product platform is supported by an intellectual property portfolio of over 100 issued patents and 100 pending patent applications.

The company’s cells of interest are the cells of the immune system. The cell therapy product candidate pipeline is comprised of immuno-oncology programs, including off-the-shelf subtypes of lymphocytes such as NK (Natural Killer) - and T-cell product candidates. Both candidates derived from master iPSC lines and immuno-regulatory programs, including products to prevent life-threatening complications in patients undergoing hematopoietic cell transplantation and to promote immune tolerance in patients with autoimmune disease. The first product in the pipeline is FT500, an off-the-shelf NK cell therapy for the treatment of advanced solid tumors. FT500 is the first iPSC-derived cell therapy approved for use in a clinical trial. The second candidate is FT516, an engineered NK tested in a Phase l/ll. FT596 has the potential to become the preferred cell therapy product for relapsed/refractory lymphoma.

0.4%

G1 Therapeutics

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G1 Therapeutics

0.4%

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 lerociclib as well as an oral selective estrogen receptor  degrader (SERD). The lead candidate, trilaciclib, is an intravenous CDK4/6 inhibitor that has proven effective in myelopreserving the bone marrow across multiple cell lineages in three clinical trials in small-cell lung cancer. Based on these data, the company is currently submitting the NDA for trilaciclib to the FDA with a potential  approval in mid-2021. The other wholly owned clinical assets, lerociclib and G1T48, are currently in proof-of-concept studies in metastatic breast cancer with relevant newsflow expected over the coming months.

0.8%

Generation Bio

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Generation Bio

0.8%

Generation Bio is an innovative genetic medicines company focused on creating a new class of gene therapy to provide durable, redosable treatments for patients suffering from both rare and prevalent diseases. Rather than using a viral vector (i.e. AAV capsid) the company uses proprietary cell targeted lipid nanoparticles (ctLNPs) to deliver their proprietary closed-ended DNA (ceDNA). Generation Bio has produced ceDNA constructs of 12 kilobases (kb), much larger than the maximum AAV capacity of 4.7 kb, enabling the design of therapies to provide targeted delivery of genetic payloads that include large and multiple genes across a broad array of tissues, and to be redosable for individualized and extended treatment throughout a patient’s life. This platform can also address disease when AAV therapy may not be working or where patients have pre-existing antibodies to the viral capsid. The proprietary, capsid-free manufacturing process uses standard biologics infrastructure, which is scalable, based on disease prevalence. Generation Bio’s current pipeline prioritizes 8 rare, monogenic disease (5 liver and 3 retina) with well-established biomarkers and regulatory pathways. The 2 lead programs are in Phenylketonuria (PKU) and Hemophilia A (Hem A), with Investigational New Drug Application expected in 2022.

4.4%

Halozyme Therapeutics

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Halozyme Therapeutics

4.4%

Halozyme Therapeutics is a biopharmaceutical company based on the Enhanze (rHuPH20) platform. Enhanze relies 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, fixed dose combination of Perjeta and Herceptin, Opdivo, efgartigimod or AXLN-1810. Halozyme is aggressively pursuing a return of capital to shareholders through share buyback programs.

0.7%

Homology Medicines

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Homology Medicines

0.7%

Homology owns a proprietary platform based on AAV vectors derived from human CD34+ cells. The company is building both a gene therapy and gene editing pipeline based on this technology which they licensed from City of Hope. Its lead program is HMI-102 which is an AAVHSC15 vector being developed for classic phenylketonuria (PKU) patients. 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 neu-rological impairment. Initial proof of concept data from a Phase I/II study showed a dose response in Phe reduction. 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 technologies that have to create single- or double-strand breaks in the patient DNA by cutting with an endo-nuclease (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.

7.6%

Incyte

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Incyte

7.6%

Incyte is focused on hematologic disorders, inflammatory disorders, and cancer. Their marketed product is Jakafi (Ruxolitinib), an oral JAK-2 inhibitor that received approval for myelofibrosis (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 the 2019 approval of Jakafi for steroid-refractory acute GvHD could add another USD 200 mn in sales. 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 re-ceives 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, as well as the development Ruxolitinib cream for  atopic dermatitis and vitiligo, continues.

0.8%

Intercept Pharmaceuticals

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Intercept Pharmaceuticals

0.8%

Intercept Pharmaceuticals is focused on the development of bile acid analogs for the treatment of 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 has posted positive pivotal trial for NASH, which is expected to be approved in early 2020. 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 only positive pivotal trial to date and the only one to have shown an antifibrotic effect on liver histology, on the flipside there are some pruritus-related tolerability worries with the drug.

2.3%

Intra-Cellular Therapies

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Intra-Cellular Therapies

2.3%

Intra-Cellular Therapies is a biopharmaceutical company developing treatments for disorders that affect the central nervous system. Their wholly owned lead therapeutic asset candidate is Caplyta (lumateperone), a 5-HT2A serotonin receptor antagonist that also modulates dopamine and serotonin transporters, which won FDA approval in late 2019 for the treatment of acute schizophrenia. Caplyta could prove highly differentiated from other anti-psychotics due to its ability to modulate multiple neurotransmitter pathways simultaneously. This was demonstrated by two positive regis-trational trials 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 Caplyta has proven to be differentiated. Intra-Cellular is also evaluating lumateperone in several Phase III trials for the treatment of bipolar depression as well as behavioral disturbances associated with dementia including Alzheimer’s disease. The company also has a selective PDE-1 inhibitor platform, currently evaluating ITI-214 in a variety of neurological, cardiovascular and immune system diseases.

11.5%

Ionis Pharmaceuticals

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Ionis Pharmaceuticals

11.5%

Ionis Pharmaceuticals is the leader in the space of antisense, with over 30 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, 2018 and 2019. 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.

0.5%

Kezar Life Sciences

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Kezar Life Sciences

0.5%

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 II proof-of-concept trial in lupus nephritis (LN) on top of current standard of care with a readout expected in 2021. Moreover, further clinical trials have been initiated to evaluate KZR-616 in further autoimmune disorders with high unmet medical need such as warm hemolytic anemia and immune-mediated and  inflammatory myopathies where proteasome inhibitors like Velcade have proven  efficacious but too toxic for chronic treatment.

3.1%

Macrogenics

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Macrogenics

3.1%

Macrogenics has multiple compounds in clinical development that were generated using its propriety Fc-optimization technology that simultaneously reduces/enhances binding to inhibitory/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. In 2020, the company hopes to file and receive approval of its first product, Margetuximab for HER2+ metastatic breast cancer, and report Phase II results on multiple pipeline compounds for cancer.

5.2%

Moderna

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Moderna

5.2%

Moderna 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 3.0 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 over 20 development candidates, with 10 of them in the clinic, for mRNA-based vaccines as well as treatments in diverse therapeutic areas. Moderna recently presented key derisking data for their CMV vaccine program as well as for an mRNA encoded chikungunya antibody as a surrogate for rare disease application. In our view, the key programs that will be reading out clinical data within  the mid-term include the rare liver disease MMA and PPA, the proprietary vaccines  in congenital CMV and hMPV+PIV3, the intratumorally injected cytokine cocktail OX40L+IL23+IL36 gamma, the personalized cancer vaccine and early data on the VEGF Phase II during CABG-surgery.

1.2%

Molecular Templates

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Molecular Templates

1.2%

Molecular Templates is a development-stage oncology company based in Texas and is engaged in the discovery and development of targeted biologic therapeutics. The proprietary drug platform technology, known as Engineered Toxin Bodies (ETBs), repre-sents a new class of targeted biologic therapy with unique biological properties. ETBs work through a novel, unique intracellular mechanism of action: enzymatic and permanent ribosome inactivation and subsequent destruction. In vitro and clinical data have demonstrated that ETB activity is neither inhibited by generalized mechanisms of chemoresistance nor by neutralizing anti-drug (against the toxin) antibodies. ETBs can induce internalization into cells even against non- or poorly internalizing targets. Forced internalization expands the universe of extracellular receptors that can be targeted for direct cell kill. MT-3724, the company’s lead ETB candidate, is immuno-toxin that targets the CD20 cell surface antigen present in a variety of lymphomas and leukemia types. Other assets in the clinic include targets CD38 (partnered with Takeda), HER2 and PDL-1 (by the end of 2020).

2.8%

Myokardia

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Myokardia

2.8%

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 mava-camtem, an allosteric inhibitor of cardiac beta myosin function that is being investigated in obstructive hypertrophic cardiomyopathy (oHCM ). 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 early 2020. Further the company is pursuing the development of mavacamtem in non-obstructive HCM as well as the second asset (MYK-491) that is being developed for genetic DCM (dilated cardiomyopathy).

2.4%

Myovant Sciences

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Myovant Sciences

2.4%

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 endometriosis. Positive Phase III data have been announced in 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 the two Phase III trials in endometriosis in early 2020. Myovant owns worldwide rights outside of Asia.

1.5%

Nektar Therapeutics

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Nektar Therapeutics

1.5%

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 and bladder cancer, and data from larger cohorts of patients with these tumor types are due in 2020. Meanwhile, a large pivotal program targeting these tumors is under-way with partner Bristol-Myers, and we look for first results in melanoma at the end of 2020.

8.9%

Neurocrine Biosciences

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Neurocrine Biosciences

8.9%

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 partnered with Abbvie and approved for endometriosis with approval for uterine fibroids expected in the second quarter of 2020. 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 potettially surgical removal of the uterus. Neurocrine is also in a collaboration with Voyager for Parkinson’s disease and other neurological indications.

2.4%

Radius Health

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Radius Health

2.4%

Radius Health is a company focused on women’s endocrinology and osteoporosis.  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 have steadily allowed it to capture significant market share. Radius received approval in 2017, and we expect 2020 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 read out in the latter half of 2021. Elacestrant, a selective estrogen receptor degrader (SERD), is in Phase III development for estrogen-receptor-positive breast cancer. The company is currently in late stage talks with potential partners and plans a near-term exit from oncology in order to strengthen its focus on endocrinology and bone health.

1.5%

Sage Therapeutics

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Sage Therapeutics

1.5%

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), was approved in 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). Several ongoing Phase III trials in MDD are expected to read out in 2020/21, after which the company may file a complete application for approval in both PPD and MDD. Sage has diverse neurology and neuropsychiatry franchises – with SAGE-324 being investigating in essential tremor, epilepsy and Parkinson’s disease, and SAGE-718 in Phase I development in cognitive disorders and Huntington’s disease.

0.9%

Sangamo Therapeutics

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Sangamo Therapeutics

0.9%

Sangamo Therapeutics is uniquely positioned as the almost exclusive developer of Zinc-finger-based genomic editing (ZFN). After initial disappointments with the ZFN in vivo applications, the company has pushed the reentry into the clinical with ZFN 2.0 to the end of 2020. Sangamo’s lead asset now is a classic gene therapy approach for hemophilia A (Phase III initiated with Pfizer) through the formulation expertise that the company gained while delivering ZFN (AAV6 capsid with AAV2 promotor/genome), which is followed by a wholly owned clinical program for Fabry’s disease. Further optionality from partnered projects include ex vivo collaborations with Sanofi (sickle cell disease and beta thalassemia) and Kite (allogenic CAR-T), gene regulation ZFP without nucleases (Shire and Pfizer) as well as wholly owned CAR-Treg program Tx-200 in kidney transplants.

1.2%

Scholar Rock

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Scholar Rock

1.2%

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 were positive with additional data expected in 2020. 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. The oncology study will begin in 2020.

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 (CF). 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 corrector 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 has also developed 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 were positive and a triple regimen received early approval in 2019, bringing the total market opportunity for its CF products to 10+ bn.

0.8%

Voyager Therapeutics

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Voyager Therapeutics

0.8%

Voyager is a clinical-stage biotech company focused on developing novel genetically targeted therapies to treat CNS diseases. In collaboration with Neurocrine, their 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 proprietary 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 the company has built an in-house, state-of-the-art production facility for manufacturing AAV vectors.

0.7%

Wave Life Sciences

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Wave Life Sciences

0.7%

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. Proof of concept data support a clean safety profile and clear target engagement, but higher doses will be added to the Phase I/II study. Wave’s second program in DMD was discontinued.

All comments as at December 31, 2019 or beginning of investment.

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Media releases / 24.07.2020

BB Biotech AG publishes its interim report