Financing repurposed drugs for rare diseases: a case study of Unravel Biosciences

Abstract Background We consider two key challenges that early-stage biotechnology firms face in developing a sustainable financing strategy and a sustainable business model: developing a valuation model for drug compounds, and choosing an appropriate operating model and corporate structure. We use the specific example of Unravel Biosciences—a therapeutics platform company that identifies novel drug targets through off-target mechanisms of existing drugs and then develops optimized new molecules—throughout the paper and explore a specific scenario of drug repurposing for rare genetic diseases. Results The first challenge consists of producing a realistic financial valuation of a potential rare disease repurposed drug compound, in this case targeting Rett syndrome. More generally, we develop a framework to value a portfolio of pairwise correlated rare disease compounds in early-stage development and quantify its risk profile. We estimate the probability of a negative return to be $$80.8\%$$ 80.8 % for a single compound and $$56.1\%$$ 56.1 % for a portfolio of 8 drugs. The probability of selling the project at a loss decreases from $$79.2\%$$ 79.2 % (phase 3) for a single compound to $$55.4\%$$ 55.4 % (phase 3) for the 8-drug portfolio. For the second challenge, we find that the choice of operating model and corporate structure is crucial for early-stage biotech startups and illustrate this point with three concrete examples. Conclusions Repurposing existing compounds offers important advantages that could help early-stage biotech startups better align their business and financing issues with their scientific and medical objectives, enter a space that is not occupied by large pharmaceutical companies, and accelerate the validation of their drug development platform

Specialization of mutualistic interaction networks decreases toward tropical latitudes

SummarySpecies-rich tropical communities are expected to be more specialized than their temperate counterparts [1–3]. Several studies have reported increasing biotic specialization toward the tropics [4–7], whereas others have not found latitudinal trends once accounting for sampling bias [8, 9] or differences in plant diversity [10, 11]. Thus, the direction of the latitudinal specialization gradient remains contentious. With an unprecedented global data set, we investigated how biotic specialization between plants and animal pollinators or seed dispersers is associated with latitude, past and contemporary climate, and plant diversity. We show that in contrast to expectation, biotic specialization of mutualistic networks is significantly lower at tropical than at temperate latitudes. Specialization was more closely related to contemporary climate than to past climate stability, suggesting that current conditions have a stronger effect on biotic specialization than historical community stability. Biotic specialization decreased with increasing local and regional plant diversity. This suggests that high specialization of mutualistic interactions is a response of pollinators and seed dispersers to low plant diversity. This could explain why the latitudinal specialization gradient is reversed relative to the latitudinal diversity gradient. Low mutualistic network specialization in the tropics suggests higher tolerance against extinctions in tropical than in temperate communities