European listed biotech landscape: 2020 review and outlook for 2021

Worst Performances of 2020


1- DBV technologies, France, -78%
See our prior comments in the Lowlights section.

2- Genfit, France, -77%
See our prior comments in the Lowlights section.

3- Asarina Pharma, Sweden, -75%
We had placed the results of the phase 2b of sepranolone in premenstrual dysphoric disorder (PMDD) in our selection of catalyst for 2020. Given the single-product profile of the company, it was likely to be a very binary event for the company. It failed, thus the huge stock fall. Now, Asarina will try to achieve a positive POC of the same sepranolone, but in menstrual migraine. Results in 2021.

4- Santhera, Switzerland, -75%
The Swiss company decided to play the win for their phase 3 SIDEROS of idebenone (Puldysa/Catena) in Duchenne Muscular Dystrophy (glucocorticoid non-users), by setting up an unplanned interim analysis. Unfortunately for Santhera, the interim analysis concluded to the futility of the study. Having filed in Europe for idebenone in DMD, Santhera withdrew their application and discontinued the program. Having negotiated an option for vamorolone sub-licensing from Reveragen through Idorsia in 2018, Santhera decided to exercise their option early (before the forecasted milestone of the phase 2b results) for vamorolone, in exchange for potentially more favorable terms. A little red flag was raised last year, with the negative outcome of Catabasis’ edasalonexent (oral NF-κB inhibitor) trial in DMD. Reveragen and Santhera hopes of a positive phase 2b will then rely on the positive phase 2a data. Results in 2021.

5- Nuformix, UK, -70%
4th best performance last year, Nuformix stock retraced a large part of the 2019 gains. No bad news from clinical trials, but just no cash, and that even those who owe cash to the company (their partner NewSummit, in dispute with their parent company) do not send them the money. No good news either.

6- Newron Pharma., Italy, -66%
The phase 2/3 of sarizotan in Rett Syndrome was a key binary even for the company. Yet another negative study. Newron had delayed the readout at the last minute, trying to “seek guidance” from the FDA on the SAP, just before the unblinding, which is never a good omen (also see Genfit phase 3 in NASH). Despite having a product on the market with Xadago as an addon to SOC in patients with Parkinson's Disease, the prospects of the follow-on programs were not really clear either. In 2019, the FDA had indeed requested more mechanistic/explanatory data on evenamide, after the agency expressed concerns on findings from a completed study in rats as well as CNS events at higher doses in dogs. The company had downplayed these concerns, saying that the issues were likely related to the animal species but that there would likely be no issues in human. With the results of the explanatory study expected early in 2021, it is then expected that the FDA gives its green light for the launch of the phase 2/3 program in schizophrenia. Unless…

7- Shield Therapeutics, UK, -65%
Ferracru was approved in the US during 2019 for the treatment of iron deficiency anemia, but the company is still no close to see the beginning of any revenue from this product. Indeed, the US partnering plans have shifted. So much that the company is now exploring the possibility to go alone on this market. After the already weird communication of 2019 with respect to the outcome of the AEGIS-H2H study testing the non-inferiority of Ferracru versus Ferinject (first announced as failed, then positive a few weeks later), a re-analysis of the study led to the conclusion that the non-inferiority was not demonstrated. Which indeed might not help the company during their partnering discussions.

8- PCI Biotech, Norway, -64%
At the end of last year, PCI Biotech had disclosed that the undisclosed partner they had worked since the end of 2015 for the evaluation of the fimaNAc platform as a drug delivery modality was nobody else than AstraZeneca. Given the size of the company, such a big name was music to the ears of the investors, who bought massively (+192% in 2019, among the best performance among the European biotech companies). The company seemed confident that a licensing agreement could be signed during the first half. Nothing happened during that period, and PCI finally announced the end of the collaboration with AstraZeneca at the end of last year. The results generated within the collaboration are to be published in a peer-reviewed journal. Data that apparently make PCI confident that the platform remains promising. A few month ago, PCI has also terminated of other collaborations with Bavarian Nordic, BioNTech, and Phio Pharmaceuticals, seemingly judging the progress too slow. Finally, the lead clinical program, finaChem or fimaporfin (Amphinex) saw significant delay in recruitment of the phase 2b in bile duct cancer (cholangiocarcinoma). Indeed, the therapy requires an intervention with a laser light, which in COVID times, was challenging to plan and perform.

9- Egetis Therapeutics / Pledpharma, Sweden, -63%
Pledpharma, renamed as Egetis at the end of last year, started off 2020 on the wrong foot. In January, the FDA issued a clinical hold for the phase 3 program of calmangafodipir (PledOx)in chemotherapy-induced peripheral neuropathy or CIPN in 2 settings for patients with mCRC. The agency had concerns on the imbalance of a safety event, that Pledpharma would not disclose more specifics. The French ANSM followed with its own clinical hold. Though, Pledpharma did not believe the imbalance was actually related to PledOx. Given the advanced stage of the recruitment, and following the DSMB recommendation to continue the study, Pledpharma performed an analysis of the available dataset at the end of 2020, by pooling the data. The outcome was negative, with no reduction of the risk of developing moderate/severe CIPN with PledOx. The rare undisclosed safety events were eventually disclosed to be severe allergic-hypersensitivity reactions occurring only after repeated treatment cycles. Now, Egetis, who acquired Rare Thyroid Therapeutics Disorders, wants to refocus on the development of calmangafodipir (Aladote), but in the prevention of paracetamol poisoning (phase 2/3 launch in 2021), as well as on tiratricol (Emcitate) in MCT8 deficiency aka Allan-Herndon-Dudley Syndrome (phase 2/3 also planned for the end of 2020 but seemingly delayed into 2021).

Other negative performances:
• Nordic Nanovector (-51%, Norway): another tough year for the company, still facing high recruitment challenges in their pivotal phase 2b trial of Betalutin in 3L Follicular Lymphoma. Amendments were filed to speed up things, but progress were slow, the COVID pandemic not helping. At the end of 2020, the management still believed that the topline results of the PARADIGME study could be obtained at the end of 2021 but nothing seems less warranted at this time (no recent feedback on the approvals of the amendments not on their implementation).
• ObsEva (-45%, Switzerland) know another terrible year in 2020, after -72% in 2019. The investors were not particularly reassured by the BMD loss data of linzagolix (Yselty – a GnRH receptor agonist) 100mg without add-back therapy from the US phase 3 in heavy menstrual bleeding associated with uterine fibroids. And this, this, despite the bast-in-class claims of the company. Nevertheless, the company filed in Europe in November. The company also disclosed POC data for ebopiprant (PGF2alpha receptor antagonist) in preterm labor. While the data are numerically better for ebopiprant versus placebo, on top of atosiban, all the 90% (not 95%) confidence intervals of the Odds Ratio overlap with 1.0. However, Obseva provided a bullish update at the JP Morgan Conference, aiming at obtaining a Breakthrough Therapy Designation in 2021, and seeking to expedite the development of ebopiprant towards registration with a single pivotal study with adaptive design. Whatever the reason, the stock of Obseva bounced signicantly since this presentation.

There was no pattern specific to any country among the 2020 worst performers.