PORTFOLIO UPDATE Q4 2020 

The fourth quarter 2020 provided multiple major milestones for our portfolio holdings such as clinical results, regulatory decisions, licensing deals and M&A transactions. The highlight in the fourth quarter was the high efficacy and good safety profile of mRNA-1273, Moderna’s prophylactic mRNA vaccine against SARS-CoV-2, leading to an emergency use authorization (EUA) by FDA in late December. Moderna has announced to deliver around 20 mn doses in December alone and in the meantime has increased its delivery capacity by upping the lower capacity range from 500 mn to 600 mn, with a continued 1 bn as peak capacity for 2021.

Promising clinical trial results

Next to the positive vaccine update, many clinical trial read-outs reported by our portfolio holdings were convincing and positive. Agios reported that 40% of patients with pyruvate kinase deficiency who are not regularly transfused achieved a sustained hemoglobin increase of more/equal 1.5 g/dl compared to 0 placebo patients. In January 2021, the company reported a second positive study in patients with pyruvate kinase deficiency being transfusion-dependent. These two studies are the basis for a regulatory filing in the first half of 2021.

Incyte reported top line results for Ruxolitinib (Jakafi) with significant improved outcomes in patients with steroid-refractory or steroid-dependent chronic graft-versus-host disease. These results complement previously reported results in steroid-refractory acute graft-versus-host disease, added to the Jakafi label in 2019. Subsequently, Incyte has raised its 2027 Jakafi US revenue guidance to above USD 3 bn.

Promising proof-of concept data was reported by Scholar Rock, Arvinas and Crispr Therapeutics, with Vertex reporting disappointing news regarding its first oral development candidate VX-814 targeting patients with alpha-1 antitrypsin deficiency. Scholar Rock announced positive interim analysis for the Phase II trial testing SRK-15, a selective inhibitor of the activation of myostatin, in patients with spinal muscle atrophy. Motor function improvement were observed at the 6-month interim analysis, with data for the 12-month treatment expected in the second quarter of 2021. Arvinas announced a robust efficacy signal for ARV-471 in heavily pretreated breast cancer patients. ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the estrogen receptor (ER). Responses in heavily pretreated breast cancer patients support Arvinas to initiate a Phase II dose expansion of ARV-471 in the first half of 2021.

Progress has been achieved and reported for our holdings developing genetic medicines. Crispr Therapeutics presented updated results for its investigational Crispr/Cas9 gene-editing therapy CTX001. The company together with its development partner Vertex disclosed now seven beta thalassemia patients treated and transfusion-independent with 3 to 18 months of follow-up after a single CTX-001 infusion. In sickle cell patients, all three patients were free of vaso-occlusive crisis with 3 to 15 months of follow-up after the CTX-001 infusion. The companies expect to enroll the last patients per end of 2021 and will continue the dialogue with regulatory authorities to set out the registration path.

Numerous milestones with regard of regulatory decisions

BB Biotech’s portfolio holdings updated on multiple regulatory decisions in the fourth quarter 2020 such as

• Margenza (margetuximab) from Macrogenics was approved by the FDA for patients pretreated metastatic HER2-positive breast cancer
• Orgovyx (relugolix) from Myovant was approved by FDA for adult patients with advanced prostate cancer
• mRNA-1273 from Moderna received an emergency use authorization (EUA) as prophylactic vaccine for SARS-CoV-2.
• Oxlumo (lumasiran) from Alnylam was approved by the FDA and the EMA for primary hyperoxaluria type 1 patients
• Agios withdrew its EMA marketing authorization application of Tibsovo (ivosidenib) to treat acute myeloid leukemia patients with IDH1 mutations

Accelerating M&A activities and beneficial collaboration in the second half of 2020

With M&A as well as business development activities slowing down in the first half of 2020, a clear re-acceleration was observed for the second half of the year. In the fourth quarter alone, four of BB Biotech’s portfolio holdings reported substantial transactions. The Myokardia takeover by Bristol Myers Squibb was completed in November in an all-cash transaction for approximately USD 13.1 bn. In late November, Sage and Biogen announced a global collaboration to develop and commercialize Zuranolone, a next-generation positive allosteric modulator of the gamma-aminobutyric acid (GABAA) receptor that is developed as an antidepressant. The deal includes as well SAGE-324, a next-generation positive allosteric modulator of GABAA receptors in Phase II development for essential tremor. A large takeover was announced in December, with AstraZeneca acquiring Alexion, with a total consideration of USD 60 per share in cash plus 2.1243 shares (AZN US), in total USD 39 bn or USD 175 per share. The companies recently updated the timelines for the deal expected to close in the third quarter of 2021. In late December, Servier agreed to acquire Agios oncology business for up to USD 2 bn plus future royalties. Agios announced to use around two thirds of these proceeds to repurchase shares and around one third to invest into its remaining genetically defined disease franchise.