The European listed biotech companies with COVID-19 programs: status & follow-up (updated 28/06/2020)

In the context of the COVID-19/SARS-Cov-2 pandemic, many biopharma companies throughout the world try to bring therapeutic options, on top of the topic of testing, which will not be focused on here. Some European listed companies have joined this international effort over the past weeks, and especially since the month of March.
Vaccine development has started in many companies, academia, or in the frame of a consortium with several stakeholders. Vaccination is theoretically the solution to obtain the "herd immunity" against the virus, if the "immunity" is confirmed, and knowing that the levels and duration of the "immunity" would still have to be characterized. There is quite a large number of vaccines in development already. It seems that the most advanced candidate in Europe comes from a British consortium led by Jenner Institute, University of Oxford. Oxford Biomedica recently joined this consortium, to bring its experience for the manufacturing, given that "at risk" production could start before the full results of the forthcoming clinical trial of this vaccine candidate are known. In the scenario where everything would go perfectly, this consortium would be ready to release the first vaccine batches in the Autumn of this year, which would be an extremely compressed timeline. Other vaccine initiatives by Moderna Therapeutics (together with the US NIH), Johnson and Johnson, CanSino, or BioNTech/Pfizer have been publicized over the past weeks. The timelines for these 2 other candidates are nevertheless more stretched, since early 2021 has been mentioned as the best-case scenario for a potential Emergency Use Authorization for Johnson and Johnson, and more mid-2021 for Moderna's vaccine to be "ready".
Concerning the virus itself and the clinical implications for the symptomatic cases, several avenues are pursued, starting with the most appropriate to address the emergency: drug repurposing. A number of papers have been published in the past weeks to propose existing drugs to be potentially repurposed to fight the COVID-19/SARS-Cov-2 coronavirus and the associated pathologies. These concerns currently approved drugs or investigational drug candidates. So far, several hundred of clinical trials have been launched, but unfortunately, no candidate has established a proven favorable benefit/risk ratio yet (at least not in the frame of an RCT). Given the increasingly large effort to find therapeutics, one may just be hopeful that several options will emerge, beyond the multiple case reports and observational studies published until now, for which it's hard to conclude anything that would be "practice-changing". Unsurprisingly, the repurposing of existing candidates is the approach of almost all the companies listed below.
The exceptions are listed the following cases:
• the UK's consortium joined by Oxford Biomedica for the ChAdOx-1 nCov19 vaccine candidate, which is a new development by definition, since the virus is new (the viral vector was already used in other candidates)
• Biotest and the internal consortium the company formed recently with Takeda, CSL and other plasma-derived product players (unique branded product based on antibodies from recovered/healed patients)
• Pharnext, whose hybrid approach consists in combining several repurposed drugs to propose new drug candidates to be tested (concept of "Pleodrugs"), using its AI/Big Data know-how
• Immupharma, via its subsidiary UREkA Pharma who recently joined a consortium to run research on viral-specific peptides, with a potential application on COVID-19 according to the company (this project seems very early and the plan seems quite vague so far)
• Avacta, for which the application is not for therapeutics but for testing
While the rationale for repurposing or for the development of new options seems interesting for some companies, it seems more questionable for others. Given that most of the companies are rushing to initiate the clinical development of their potential options, the level of evidence can only be globally low, if existing. Some companies haven't published any supporting data, which should be a minimum, even on a preprint or on the company website. One exception might be the Biotest case, for which the approach seems relatively de-risked, relying mainly on the execution. In contrast, the risk level seems more important for the approach pursued by Vicore (and likely also by Biophytis), betting on a potential role of an imbalance in the Renin-Angiotensin System induced by a "hijacking" of ACE2 by the virus, which is basically unproven at this date. In fact, the RAS (or RAAS) system has rapidly been the subject of a controversy, as ACE inhibitors and ARBs were shown to upregulate ACE2 expression on cell surface, possibly in the lungs. As ACE2 is one cell entry of the virus, there were concerns about a potentially increased risks of bad outcome for infected patients treated with these anti-hypertensive therapies (Vaduganathan et al., NEJM). However, a study published this week, in which patients under ACE inhibitors and ARBs did even better that those who did not, seemed to support the alternative thesis by Vaduganathan et al. Their thesis proposes, on the contrary, that ACE inhibitors and ARBs could help maintaining the balance between ACE2 (downregulated by the virus), and Angiotensin II, by decreasing the activity of the latter. If confirmed with more data or other studies, this could indeed give some credit to the concept of RAS imbalance, however ACE inhibitors and ARBs would also be straightforward and immediate solutions. Another point is that ACE inhibitors and ARBs potentially upregulate ACE2 expression, so how one contribution would offset the other? In short, there is no definitive conclusion on the RAS system involvement, and more studies are needed, but things do not always work as expected initially.
Our comments on the low level of evidence applies also for all the other companies with in vitro data only. In fact, there is no gold standard models for SARS-Cov-2 animal models, which is why there is no data in vivo for this virus. The development of such models is also a challenge. Then you have companies with some in vivo experiments, but in animal disease models for which the relevance is often hard to appreciate, due to the mechanisms inducing these diseases that would not recapitulate what happens with the virus. But do we really know what happens? More Interestingly, a few companies can find some support in human data, within the collection of off-label cases reported (see table references), like for the antibodies collected from healed patients, or the anti-cytokines, in particular anti-IL-6/IL-6Rs.
At the end of the day, some approaches might be invalidated or weakened in terms of rationale, even before launching the clinical trials. One can mention the case of Kaletra, studied in the Discovery trial piloted by the French INSERM, whereas RCT data published in the NEJM before the trial launch seemed to indicate a weaker-than-thought rationale. The risk mainly comes from the many unknowns on the virus, the research on the virus is still in its infancy and the knowledge of tomorrow might already challenge the assumptions we hold today. However, the investors' appetite for "the COVID stocks" has been important over the past weeks, and it could have led to some excess of optimism in terms of valuation. The most interesting example being the one of MedinCell, whose valuation jumped by 100 mEUR just on the disclosure of their research project. This program concerns the repurposing of ivermectin in a long-acting injectable, and is only based, for now, on in vitro experiments by an academic institution. Probably one of the most profitable Petri dish work ever in the history of biotech, since it costed 0 EUR to the company.
Therefore, the list established today is certainly called to expand even further in the next weeks. As no one really knows if the virus will come back periodically on a seasonal basis, how immunity has developed so far in the populations, how long it may last, and how far we are from a decent vaccine solution, the gap remains to be filled. This leaves an open door for speculation that some companies have already used, generally opportunistically. This door will close progressively over time when some agents will emerge, so the investors interest will fade at some point, but the timeframe for which the window will remain open in the investors' mind is currently undefined. Another caveat inviting to moderation is that many clinical trials will be performed in a small number of patients, in populations probably not optimally defined, so the expectations in terms of outcome should be globally relatively moderate. There is also the issue that after the mitigation measures, the number of cases in many Western countries could remain low (at least this is the plan), making clinical investigations more difficult to run in the coming months. Meanwhile, one can only endorse the current effort, wishing these companies the best.
The table below keeps track of the different programs disclosed by the European listed companies (mainly listed in European stock markets). Most of these companies are covered in the frame of our service. You will find the main information on these programs, as well as some relevant market data. The data -all accessible to the public- will be updated as data comes in.
On 20/04/2020, Molecular Partners disclosed a program for trispecific DARPin® molecules targeting the spike protein of COVID-19/SARS-Cov-2. This program could be one of the most promising, and not only for the European biotechs, but more globally, while waiting for an efficacious vaccine. As big biotechs/pharmas will develop biologics for the same purpose (neutralizing the virus by blocking the known cell entries, with multi-specific constructs or not), as disclosed by Regeneron, the DARPin approach of Molecular Partners could be a tour de force, adding multi-specificity for a potentially improved efficacy. On top of that, GMP manufacturing could be ready relatively rapidly (Q3 2020), competing with the most aggressive timelines for biologics manufacturing.
Then Valneva, together with Dynavax on 22/04, and Scancell on 24/04, both announced their respective vaccine programs. Of note, China Sinovac already entered in the clinics last week with an inactivated-virus vaccine (the same approach as Valneva). Sinovac's preprint on their vaccine candidate was also recently published. In addition, still on the topic of vaccines, you can have a look at these 2 posts by Derek Lowe on his Science blog (recommended one), here (prospects) and there for a review of the most advanced vaccine programs. According to another recent lanscape review on the COVID-19 vaccines, as of 08/04, there were not less than 115 vaccine programs, of which 78 confirmed. On 05/05, OSE Immunotherapeutics has joined the efforts towards the development of prophylactic vaccines. Given the number of vaccines in development, and the financial means of these companies, the expectations towards crossing the finish lines should be relatively low. Valneva and Dynavax will likely seek some more financing. Scancell has already said that they would need to partner their program at some point, and so would OSE Immunotherapeutics.
On 14/05, ABIVAX announced a broad phase 2/3 in 1034 patients, to investigate the efficacy and safety of ABX464 in a range of COVID-19 patients. The study was approved to begin in France, expected to be expanded in Europe in the short term. Of note, the company also managed to collect a sizeable amount of 36mEUR of grants and loans from BPIfrance, mainly to finance the costs of the study and support the costs associated with the scale-up of the manufacturing.
Since our end of May update, GSK started a clinical trial of otilimab. Remdesivir was approved on 25/06 in Europe (approved since early May in the US). Dexamethasone was shown to reduce mortality risks by around 30% in critically-ill patients (RECOVERY RCT), whereas the testing of hydroxychloroquine has been withdrawn by most of the institutions, due to a lack of efficacy.
As of 28/06, 43 (+6 versus 25/05) European biotech companies (mostly within our coverage or around 28% of the field) have officially initiated a program relating to COVID-19, out of approximately 152 listed biotech companies. 14 programs are in active clinical trials.
Finally, one may find more information on clinical trials against COVID-19 on 2 external resources, here and there.

Table updated on 28/06/2020

Company Product Candidate Indication / Application Mechanism of Action Dev. Stage Clinical Trial 1st PR disclosure Supportive Publications Comments Stock Perf (%) 28/02 - 28/06 Raised Money?
Oxford Biomedica (UK) - OXB Viral Vector Platform / Manufacturing of AZD1222 (ChAdOx1 nCOV-19 vaccine) Prophylactic vaccine against SARS-Cov-2 Vectorized SARS-Cov-2 Spike protein in a chimpanzee adenovirus (Intramuscular) Phase 1/2 ongoing (fully enrolled)COV001 - UK08/04/2020 PR MERS vaccine in animals: Nature (camels), Vaccine (mice) OBX joined a consortium led by the Jenner Institute & Univ. of Oxford to rapidly develop, scale-up and manufacture a potential vaccine candidate for COVID-19, strong immune response from 1 dose and good safety profile in pre-clinical and clinical trials conducted to date. Trial initiated 15/04/2020. +18.1

Yes (40m£)
Morphosys (DE) via GSK - MOR otilimab; GSK3196165; MOR103 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection with pot. antiviral activity anti-GM-CSF mAb (IV) Phase 2 ongoingOSCAR; 214094 07/05/2020 Morphosys Conf. Call, GSK news Various reviews, Nature publication RCT launched in May by GSK. Addresses the immune hyperactivation aspect of the disease. +20.4 (new entry) No
Synairgen (UK) - SNG SNG001; AZD9412 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection with pot. antiviral activity IFN-β 1A (Inhaled) Phase 2 ongoing (hospital setting cohort fully enrolled)SG016 - UK18/03/2020 PRPreprint (external) and Synairgen website Listed among potential candidates by the WHO, antiviral action documented in vitro against SARS-Cov-2 (external), and against MERS-Cov (Synairgen). Trial expanded to home setting in addition to hospital setting, and to all the UK territory. Interim results epxected in July 2020. Impact of dexamethasone as potential SOC in critical patients to be assesed. +156.9

Yes (13.9m£)
Faron Pharma. (FI) - FARN FP-1201-lyo (Traumakine) ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection (pot. antiviral activity?) IFN-β 1A (IV) Phase 4 ongoing (COVID-19 Extension)REMAP-CAP - International, WHO Solidarity - 90 countries01/04/2020 PR same as Synairgen (external) Same as Synairgen, previous phase 3 in ARDS failed assumedly due to deleterious effect of concomittant corticosteroids. Part of a global initiative extended for COVID-19, with potential head-to-head data versus corticosteroids in this new study. No documented antiviral activity, conversely to Synairgen. Tested in REMAP-COVID trial and in country-arms of WHO's Solidarity trial. Traumakien also planned in the HIBISCUS study. Impact of dexamethasone as potential SOC in critical patients to be assesed. +3.8

Yes (14m€)
Relief Therapeutics (CH) with NeuroRx - RLF RLF-100 (Aviptadil) ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Vasoactive Intestinal Polypeptide (IV or via endotracheal tube) Phase 2 ongoingCOVID-AIV - US/IL17/03/2020 PR None found Program sponsored by NeuroRx (US partner). VIP is a naturally-occurring peptide hormone known to be concentrated in the lungs, shown in 5 animal species, woth potent effect in models of ARDS and Acute Lung Injury (potent anti-inflammatory and specifically anti-cytokine activity in the lungs). Previous trial of VIP in ARDS patients with sepsis: 7/8 patients on mechanical ventilation with substantial improvement / 6 discharged alive (no publication provided/found). Fast-Track Designation on 24/06/2020. +1366.7

Cosmo Pharma. (IT) via RedHill - COPN opaganib; ABC294640 (Yeliva) SARS-Cov-2 virus replication inhibition Sphingosine Kinase-2 (SK2) Inhibitor (Oral) Phase 4 ongoing (Compassionate Use) TBC - IT06/04/2020 PRAntiviral Research publication (external), Thorax publication (external) Compassionate Use authorized in Italy, clinical testing started in Israel - same to follow in Italy. Anti-viral and anti-inflammatory activities shown in preclinical experiments, with the potential to reduce lung inflammatory disorders such as pneumonia, and mitigate pulmonary fibrotic damage. Potential role of SK2 in the replication-transcription complex of positive-strand ssRNA viruses similar to coronavirus, which could lead to inhibit viral replication. Decreased fatality rates from influenza-virus infection and ameliorated Pseudomonas aeruginosa-induced lung injury. Potential deal between Cosmo and RedHill if efficacy confirmed. +21

(mostly unrelated to COVID)
Innate Pharma (FR) - IPH/IPHA IPH5401; avdoralimab ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection anti-C5aR mAb (IV) Phase 2 ongoingFORCE - FR27/03/2020 comm., 04/03/2020 PRNature publication (external), Preprint (external), Competitor's data on file (external) IPH joined the exploratory research project EXPLORE COVID-19 with the goal to better understand the immune response to SARS-CoV-2 and explore new ways to fight against it. Growing evidence of potential benefit of complement pathway blockade in hyper-inflammated subtype of COVID-19 infection => InflaRx launched a clinical trial to evaluate IFX-01 (anti-C5a) in COVID-19-associated pneumonia, based internal preclinical data and on human data in n=2 from Chinese partner / Alexion's Soliris & Ultomiris are also studied in clinical trials / cf. also Pharming C1inh. Potential role of upregulated immune checkpoints (NKG2A) published in a Nature paper. First phase 2 patient dosed with IPH5401 at the end of APril, n=108 - 2 cohorts by baseline pneumonia severity. -10.5

BergenBio (NO) - BGBIO bemcentinib; BGB324; R248 Blockade of SARS-Cov-2 virus cell entry AXL Inhibitor (Oral) Phase 2 ongoingACCORD 2 - UK28/04/2020 PRBGBIO presentation bemcentinib has been selected as the first potential treatment to be fast-tracked in a new UK national multi-centre randomised Phase II initiative to test bemcentinib's effectiveness in the most vulnerable patients with COVID-19. The ACcelerating COVID-19 R&D platform (ACCORD) study is being funded by the DHSC and UKRI. bemcentinib has been reported to exhibit potent anti-viral activity in preclinical models against several enveloped viruses (eg Ebola and Zika virus). Recent data have expanded this to SARS-CoV-2. bemcentinib selectively inhibits AXL kinase activity, blocking viral entry and enhancing the anti-viral type I interferon response, a key cellular defence mechanism against viral infection. +161.3

Yes (500mNOK)
PharmaMar (ES) - PHM plitidepsin (Aplidin) SARS-Cov-2 virus replication inhibition Elongation Factor 1A (IV) Phase 2 ongoingAPLICOV-PC; APL-D-002-20 - ES13/03/2020 PR Data on file (external) Antiviral activity in vitro against the human coronavirus HCoV-229E and previously against other viruses, no published data +93.4

(mostly unrelated to COVID)
4D Pharma (UK) - DDDD MRx0004; MRx-4DP0004 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Bifidobacterium Breve Bacteria (Oral) Phase 2 (CTA cleared 20/04 - starting in May but unconfirmed so far)MRx-4DP0004-II-001 - UK20/04/2020 PRNature paper (asthma) Currently investigated in asthma (phase I/II), reduction of lung inflammation and potential impact on particular immune cell types and pathways which have more recently been implicated in the hyperinflammatory response to SARS-CoV-2 infection. Significant reduction of airway inflammation (neutrophils, eosinophils, activated DCs) in PC models of asthma, reduction of pro-inflammatory cytokines in lung tissues with systemic immunomodulatory effects. Relevant immunomodulatory effect in the COVID-19 context? -15.5

Vicore Pharma (SE) - VICO C21 ARDS linked to COVID-19/SARS-Cov-2 infection Angiotensin II Type 2 Receptor (AT2R) Agonist (Oral) Phase 2a ongoingATTRACT - UK31/03/2020 PR Data on file (Vicore), rationale/Vicore presentation #1, Vicore presentation #2 Relevance of RAS pathway in COVID-19-related ARDS? No published data for C21 in a context relevant to COVID-19. Approach not aiming to treat the most severe cases but to prevent worsening. Molecule investigated in IPF (phase 2a to be started) & Raynaud phenomenon in SSc patients (phase 2a) but efficacy still unproven in these chronic indications. Same pathway leveraged by Biophytis (different branch of RAS pathway). Results in Q4'2020. +44.9

No (1.8m£ grant from LifeArc)
Biophytis (FR) - ALBPS Sarconeos; BIO 101 ARDS linked to COVID-19/SARS-Cov-2 infection Mas Receptor Agonist (Oral) Phase 2/3 (adaptive design) - CTA cleared in BE & UKCOVA - FR07/04/2020 PR Data on file (Biophytis) Presumably same questions on rationale/pathway as Vicore Pharma (different branch of RAS pathway but same expected effects). Unpublished in vivo data showing a restoration of normal respiratory function in several experimental models (which -relevant- ones?). The company did not explain the exact MoA expected to bring a benefit in ARDS. +209.1

Yes (4m€, plus Warrants Issue launched)
Abivax (FR) - ABVX ABX464 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Dynamin 2 Down-modulation (Antiviral); miR124 Splicing Enhancer; IL-22 Amplifier; IL-6/TNF/MCP-1 Down-regulation (Anti-Inflammatory) Phase 2/3 (CTA cleared in EU & BR)MiR-AGE16/03/2020 PR, 14/05/2020 PRCorporate Presentation European Phase 2/3 cleared in France, 36mEUR grants & loans collected via BPIfrance to finance the clinical trial and the manufacturing/scale-up. ABX464 prevents and reduces inflammation (already tested in UC). ABX464 has been shown to upregulate miR-124 which down-regulates the multiple pro-inflammatory chemo- and cytokines involved in the COVID-19 cytokine storm. ABX464 reduces viral replication, mediated by RNA quality control and miR-124 induced inhibition of dynamin 2, a key component necessary for viral replication. Finally, it promotes tissue repair and decrease pulmonary fibrosis. +56.8

Yes (36m€ grants & loans)
Evgen (UK) - EVG SFX-01; sulforaphane (Sulforadex) ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Nrf2; STAT3 Phase 2/3 to be started in July 2020 N/A - UK17/06/2020 PR Data on file (Evgen) SFX-01 upregulates the Nrf2 pathway which is part of the natural human defence against inflammatory and oxidative stress, such as the inflammation that occurs during a severe viral infection. Preclinical studies have shown that up-regulating the Nrf2 pathway reduces the severity of ARDS, the progressive lung damage observed in COVID-19 patients which can result in the need for invasive ventilation in an intensive care unit. Trial led by British Lung Foundation Professor of Respiratory Research (Univers. of Dundee). The study will recruit up to 300 patients with confirmed or suspected COVID-19 from hospitals across the UK, and is expected to begin enrolment in July, with results in 2021. +156 (new entry) No (but grant from LifeArc)
argen-x (BE) - ARGX ARGX-117 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Complement C2 Inhibitor Phase 1/2 ongoingARGX-117-2001 - BE14/05/2020 PR N/A ARGX-117 is a potentially first-in-class complement-targeting antibody against C2 with potential therapeutic applications in severe autoimmune diseases. argenx is sponsoring a Phase 1 trial in collaboration with Ghent University Hospital to evaluate ARGX-117 as a potential treatment for COVID-19-related ARDS. Both classical and lectin pathways of complement system are active in ARDS; by targeting C2, an important component of both pathways, ARGX-117 could inhibit downstream inflammatory responses associated with ARDS. +62.4

(totally unrelated to COVID)
Oryzon Genomics (ES) - ORY ORY-2001; vafidemstat ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Dual LSD1-MAO-B Inhibitor; LSD1; MAO-B; KDM1A; Lysine Specific Histone Demethylase 1 (Oral) Phase 2 ongoingESCAPE - ES24/04/2020 PR Data on file (Oryzon): preclinical data, ETHEREAL study biomarkers Open-label, randomized, double-arm Phase 2 trial of vafidemstat in combination with standard of care treatment, to prevent progression to ARDS (n=40). ESCAPE's aim is to explore a therapeutic intervention to prevent progression to ARDS which results from a so-called "cytokine storm". As with the MERS-CoV epidemic, in the COVID-19 pandemic it has been observed that the cytokines IL-6 and IL-1B are central to triggering this cytokine storm. In acute PC models of inflammation, vafidemstat has been shown to produce a rapid and strong decrease in IL-6, IL-1B and other relevant immunomodulatory inflammatory cytokines such as TNF-alpha and IFN-Gamma. In a recent clinical study (ETHERAL Study in AD), it has been shown to be very safe and it demonstrated a significant decrease in a relevant marker of brain inflammation. +0.4

Pharming Group (NL) - PHARM rhC1INH; conestat alfa (Ruconest) ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Recombinant Human C1 Esterase Inhibitor (IV) Phase 2 ongoing2020-01252; me20Osthoff3 - CH21/04/2020 PR Compassionate Use in n=5 4 male & 1 female COVID-19 patients (53-85y) suffering from related severe pneumonia, who did not improve despite standard treatment, incl. HCQ & Kaletra, administered with RUCONEST® under Compassionate Use at an initial dose of 8400U, followed by 4200U every 12hrs for 3 additional doses, no allergic reactions or drug related AEs reported => fever resolved in 4/5 patients within 48hrs, with a significant decrease in laboratory markers of inflammation (CRP, IL-6) => patients discharged (fully recovered) / 1 patient temporarily transferred to the ICU but recovered and released from the ICU. Growing evidence of potential benefit of complement pathway blockade in hyper-inflammated subtype of COVID-19 infection (InflaRx, Alexion, Innate Pharma). New IST in n=150 patients planned in Switzerland. +5.4

AB Science (FR) - AB masitinib mesylate ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Multi-kinase Inhibitor incl. CSF1R Inhibitor (Oral) Phase 2 ongoingAB20001 - FR06/05/2020 PR N/A Phase 2 (RCT) in 200 patients approved by the French ANSM, to test AB's masitinib (already investigated in many indications) in COVID-19. The combination of masitinib and isoquercetin may prevent the development of the "cytokine storm" that leads to severe pulmonary inflammation and various thrombotic events associated with ARDS and potentially death. Masitinib is a potent blocker of mast cells and macrophages that contribute to the cytokine storm. Isoquercetin inhibits disulfide isomerase, an enzyme directly involved in the formation of clots and decreases D-Dimer, a predictor of COVID-19 thrombosis severity. The combination has a synergistic effect against senescent cells, a potential target of the virus that could explain the higher mortality rates in the elderly. +24.7

Puretech Health (UK) - PRTC LYT-100; deupirfenidone; SD-560 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection TGF-β Downregulator; TGF-Beta Downregulator; Collagen Synthesis Inhibitor (Oral) Phase 2 to be started in Q3'20 N/A28/05/2020 PR N/A YT-100 (deuterated analogue of pirfenidone) employs a multimodal mechanism of action to potentially reduce, delay or prevent the lung dysfunction that has recently been documented in COVID-19 patients, including those who have recovered from the infection. The global, randomised, placebo-controlled trial is expected to begin in Q3 2020 and will evaluate LYT-100 in non-critical COVID-19 patients with respiratory complications. Patients will continue treatment for up to 3 months. +89.8 (new entry) No
Kancera (SE) - KAN KAND567; AZD8797 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection CX3CR1; Allosteric Fractalkine Receptor Antagonist (Oral) Phase 2 (CTA filed) N/A13/05/2020 PR N/A KAND567 works by blocking the Fractalkine receptor. The receptor plays a key role when the body's immune system initiates the inflammatory process. Because KAND567 acts selectively only against cytotoxic immune cells, treatment is expected to support the immune system's ability to fight the virus that causes covid-19 with antibodies. Collaboration initiated to run a Phase 2 clinical trial of KAND567 in patients with covid-19 (40 patients, open-label, KAND567 on top of SOC versus SOC only). +410.2

Yes (61mSEK share issue & 22mSEK from warrants)
Bavarian Nordic (DK) - BAVA VLP-COVID vaccine Prophylactic vaccine against SARS-Cov-2 Capsid VLP Mimicking a SARS-Cov-2 Subunit Preclinical N/A06/04/2020 PR N/A Exclusive head of terms agreement signed with AdaptVac to license their proprietary capsid virus like particle (VLP) based SARS-CoV-2 subunit vaccine. AdaptVac’s technology has the potential to mimic a virus to the body’s immune system, giving the optimal stimulus to generate a fast, long-lasting immune response that offers a highly efficacious protection. Importantly, the production of the vaccine technology can be readily scaled to commercial quantities. Bavarian Nordic will support the achievement of a clinical POC and takes responsibility for clinical development and global commercialization of the vaccine. Current plan is to initiate a clinical study later this year. -15

Biotest (DE) - BIO Polyclonal Hyperimmunoglobulin SARS-Cov-2 direct virus neutralization/killing Antibodies from the plasma of healed patients (IV) Preclinical N/A06/04/2020 Joint PRn=10 (PNAS, external) & n=5 (JAMA, external) Strong rationale, published case reports (small n's) with favorable outcome, part of the CoVIg-19 international consortium with Takeda, CSL Behring & others to develop a common trademark product +13.2

Molecular partners (CH) - MOLN MP0420 COVID-19/SARS-Cov-2 direct virus neutralization Tri-specific DARPin binding 3 sites of COVID-19/SARS-Cov-2 Spike Protein (IV?) Preclinical N/A20/04/2020 PR Data on file (together with Swiss Federal Office for Civil Protection) Multiple potent monospecific DARPin proteins neutralizing samples of the SARS-CoV-2 virus identified, targeting 3 parts of the viral “spike” protein. Multispecific inhibition represents a differentiated approach, offering potentially greater therapeutic efficacy and reduced potential for the development of viral drug resistance. Preliminary data indicate that multispecific DARPin molecules show synergistic antiviral activity, exceeding the activity of their constituent parts. GMP Manufacturing potentially as soon as Q3 2020. -24.9

(mostly unrelated to COVID)
Formycon (DE) - FYB Neutralizing Antibodies COVID-19/SARS-Cov-2 direct virus neutralization Undisclosed SARS-Cov-2-specific Antibodies Preclinical N/A29/04/2020 PR N/A Formycon develops biological COVID-19 drugs using its clinically validated antibody-based protein drug technology platform to screen for SARS-CoV-2 blocking antibody-based drugs. Antibody-based COVID-19 drugs are being designed by computer modeling to achieve the desired specific function, efficacy and safety. Formycon has established collaborations with renowned academic and industrial partners in this field and could already identify 8 candidates for further testing. The results of preclinical development are expected in Q4 2020, with potential clinical testing to be initiated in Q3 2021. -4.9

Tiziana Life Sci. (UK) - TILS/TLSA TZLS-501; NI-1201 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Fully-Human anti-IL-6R mAb (Inhaled) Preclinical N/A11/03/2020 PR rationale refs: Preprint / Science, tocilizumab refs: Preprint n=20 (external), Preprint n=1 (Annals of Onco., external) & n=1 (Blood Adv., external) Good MoA rationale addressing the "cytokine storm effect", exacerbated in the lung of many severe patients, but with the potential drawback of weakening the immune system at a too low level to fight the virus. Several favorable case reports published. Mee-too approach (several anti-IL-6/IL-6R merketed drugs already in clinical trials), so questions remain on the actual aedge of inhaled delivery versus existing drugs in terms of outcome in the real world, and on time-to-market. Corticosteroids/anti-GM-CSF/anti-IL-1 as potential alternative approaches already studied (incl. inhaled CS). +308.2

Yes (29m€ in multiple operations)
Heidelberg Pharma (DE) via RedHill - WL6 upamostat; RHB-107; WX-691; WX-UK1 (MESUPRON) Blockade of SARS-Cov-2 virus cell entry urokinase Plasminogen Activator; Serine Protease Inhibitor (Oral) Preclinical N/A19/03/2020 PR N/A RedHill intends to test upamostat in combination with other drug candidates in an exploratory COVID-19 program, indications of an anti-viral activity in preclinical experiments, no published data with activity on TMPRSS2 (apparently relevant for cell entry) +93.5

Yes (14.4m€)
N4 Pharma (UK) - N4P Nuvec platform Vaccine-like approach against SARS-Cov-2 SARS-Cov-2 Plasmid DNA in Silica Nanoparticles Preclinical N/A25/03/2020 PR N/A Program aiming to license Nuvec to partners developing vaccines for COVID-19. In vitro & in vivo POC to be established in Q2 and Q3 2020, respectively. First, N4P will demonstrate that Nuvec is capable of loading the COVID-19 plasmid and transfecting murine PBMC cells in vitro, thereby inducing an expression of the spike protein in target cells. If in vitro data are positive, an initial pre in vivo study will attempt to demonstrate the expression of the spike protein in target cells in a murine target. Inconsistencies reported between in vitro & in vivo data with the last Nuvec formulation (improved formulation ready?). +36.2

Yes (2m£)
Oncology Venture (DK) - OV 2X-121; E7449 SARS-Cov-2 virus replication inhibition PARP Inhibitor; Tankyrase 1/2 Inhibitor Preclinical N/A22/04/2020 PRPreprint (External) Preclinical program launched with the Pathogen and Microbiome Institute at Northern Arizona University (NAU), based on in vitro findings published in a preprint paper. If the study results for 2X-121 are positive, OV will advance to human clinical studies as a potential antiviral therapy for the treatment of COVID-19. -36.7

Yes (5mUSD secured)
Pharnext (FR) - ALPHA Pleodrug (AI-assisted drug repurposing) TBD pot. antiviral combo against SARS-Cov-2 TBD TBD (pot. multiple drug combo) Preclinical N/A23/03/2020 PRPreprint (Pharnext) 97 candidate drugs identified for repurposing thanks to AI/Big Data, most of which are not known to have antiviral activities, research collaboration with IHU Marseille to perform the in vitro testing of monotherapies & combinations identified by Pharnext via its AI platform. -32.5

Santhera (CH) - SANN lonodelestat; POL6014 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection human Neutrophil Elastase Inhibitor Preclinical N/A27/04/2020 PRJEM publication (external - CSHL) Collaboration w/ Cold Spring Harbor Laboratory to investigate the potential of lonodelestat (POL6014), a potent inhibitor of human neutrophil elastase (hNE), as a therapeutic intervention for COVID-19-related ARDS (preclinical evaluation). -3.3

Xintela (SE) - XINT XSTEM-COVID ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Immunomodulatory Stem Cells Preclinical N/A08/05/2020 PR N/A Preclinical study to evaluate the safety and efficacy of Xintela's Mesenchymal Stem Cells (XSTEM) in a preclinical model for ARDS, a disease condition that can affect Covid-19 patients. If the study is successful, the results will form the basis to carry out clinical studies on COVID-19 patients with severe and deadly lung symptoms. -21.3

No (1mSEK Vinnova grant, offering ongoing)
Avacta (UK) - AVCT anti-SARS-Cov-2 Affimers COVID-19/SARS-Cov-2 direct virus neutralization anti-SARS-Cov-2 Spike Protein Affimers (neutralizing antibody mimetics) Preclinical N/A15/05/2020 PR N/A Avacta has successfully generated a large number of Affimer reagents that bind to the SARS-COV-2 virus' spike protein as part of its partnership with Cytiva. Further work at Avacta has shown that several of these Affimer reagents block the interaction between the virus' spike protein and the ACE2 receptor. Avacta is seeking a partner that has the resources available to develop a neutralising Affimer therapy as quickly as possible. +458.2

Yes (53.8m£ in multiple operations)
Tiziana Life Sci. (UK) - TILS/TLSA NP-Actinomycin D; NP-Act D; NP-Dactinomycin ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Antibiotic; RNA-polymerase Inhibitor (IV) Preclinical N/A27/04/2020 PR N/A Provisional patent application on the combination of nanoparticle-Actinomycin D (NP-ACT D) with anti-IL-6 receptor monoclonal antibody as a potential therapy for management of COVID-19. The underlying invention concepts are based on the hypothesis that a combination of an antiviral drug controlling proliferation of COVID-19, with an anti-inflammatory agent suppressing a possible "Cytokine Storm" may provide immediate relief to severe cases of COVID-19. Tiziana believes it is possible to potentially combine TZLS-501 with NP-Act D to inhibit viral proliferation and to suppress inflammation in lungs to halt progression of COVID-19-mediated lung damage and death. +308.2

Yes (29m€ in multiple operations)
ValiRx (UK) - VAL VAL201 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Anti-Androgen Peptides; Androgen Receptor/SRC SH3 Domain Complex Pathway Inhibitor; SRC Kinase Inhibitor (SC) - in combination with 1 or 2 undisclosed treatments Preclinical N/A02/06/2020 PR N/A Collaboration agreement signed with Oncolytika Limited and Black Cat Bio Limited to explore the use of VAL201 in a combination treatment for patients suffering a hyperimmune response to Coronavirus SARS-CoV2 infection. Many patients infected with SARS-CoV2 exhibit more severe symptoms, with significant damage believed to be caused by an excessive response of the immune system, even after the viral infection has reduced. Oncolytika, a private UK based technical consultancy, has proposed a combination therapy which includes a selective SRC kinase inhibitor, alongside 1 or 2 complementary treatments to treat the excessive response of the immune system. Oncolytika and Black Cat have filed a patent to protect the proposed use of the combination therapy. -11.4

Yes (1.2m£ in multiple operations)
Annexin Pharmaceuticals (SE) - ANNX ANXV ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Annexin A5 Preclinical N/A17/06/2020 PR (Swedish) Data on file (from external researchers) Annexin Pharmaceuticals recently reviewed unpublished data from reputable researchers pointing out that a malignant process in patients with covid-19 is driven by the intrinsic substance phosphatidylserine (PS), which is the molecule that binds Annexin A5 / ANXV and thereby neutralizing it. The mechanism does not affect the virus's ability to infect itself, but blocking PS can potentially reduce the risk of developing life-threatening conditions. Canadian study launched with Annexin A5 (but seemingly not ANXV) in patients with COVID-19 with concomittent sepsis. +35.3 (new entry) No
Valneva (FR) - VLA VLA 2001 Prophylactic vaccine against SARS-Cov-2 Inactivated-virus Vaccine of SARS-Cov-2 with preserved Spike Protein and adjuvanted with CpG 1018 (TLR-9 agonist) Research (Phase 1 launch by YE'20) N/A22/04/2020 PR N/A Collaboration with Dynavax to initiate a vaccine program for COVID-19. Valneva is leveraging its well-established platform while Dynavax is contributing with its TLR-9 agonsit adjuvant CpG 1018. VLA2001 is a Vero-cell based, highly purified inactivated vaccine candidate against SARS-COV-2, leveraging the manufacturing technology for Valneva's JEV Vaccine. The process includes inactivation with Betapropiolactone to preserve the native structure of the S protein. The combination with CpG 1018 is expected to induce a strong immune response and has the potential to generate high titers of nAbs. A phase 1 is anticipated by year end. +55.9

(Mostly owing to its Lyme vaccine deal w/ Pfizer)
Scancell (UK) - SCLP SCIB-COVID Prophylactic vaccine against SARS-Cov-2 DNA Plasmid Vaccine aiming at inducing NAbs against SARS-Cov-2 Spike Protein RBD & Nucleocapsid Research (Phase 1 launch anticipated Q1'21) COVIDITY24/04/2020 PR N/A Collaboration with UK third parties. Scancell's DNA vaccines target DCs to stimulate high avidity T cells that survey and destroy diseased cells (same approach as with Scancell's lead ImmunoBody cancer vaccine, SCIB1). Scancell's aim is to produce a simple, safe, cost-effective and scalable vaccine to induce both durable T cell responses and virus neutralising antibodies against SARS-Cov-2. Although other vaccines may reach the clinic earlier, Scancell believes its combined T cell and antibody approach should give more potent and long-lasting responses, ultimately leading to better protection. Scancell anticipates initiating a Phase 1 clinical trial in Q1 2021, subject to funding, and is actively seeking development partners. -12.9

No (Looking for funds)
OSE Immuno. (FR) - OSE COVEPIT Prophylactic vaccine against SARS-Cov-2 Selected SARS-Cov-2 Neo-epitopes/HLA Combinations Research (pot. Phase 1 launch anticipated H2'20) N/A05/05/2020 PR N/A OSE has screened a large number of peptides derived from different proteins of coronaviruses and selected the immuno-dominant epitopes from 4 major proteins of these viruses. OSE is collaborating with deeptech company MAbSilico to accelerate optimization of these neo-epitopes and increase their immunogenicity capacity to induce robust T cell memory immunity. >20000 SARS-CoV-2 neo-epitopes and as many peptide / HLA structural models have been evaluated. OSE has selected the most specific epitopes with high potential for immunogenicity to move into preclinical testing and validate efficacy of the vaccine. +63.3

(perf. owing to non-COVID data)
Hemogenyx (UK) - HEMO HEMO-COVID-nAbs SARS-Cov-2 direct virus neutralization Neutralizing Antibodies (from proprietary Humanized Mice model) Research N/A22/04/2020 PR N/A Using its humanized mice "ApbHC", Hemogenyx will seek to discover human neutralizing antibodies that could be used to fight SARS-CoV-2/COVID-19 infections. Concurrently, Hemogenyx has initiated a pilot study that if successful, would allow them to develop and commercialize a test that could identify people with potentially high/low risk of severe illness caused by the virus. +235.3

Yes (2.5m£)
Immupharma (UK) - IMM Urelix Platform / Peptide TBD Blockade of SARS-Cov-2 virus cell entry Peptides specific for viral fusion proteins (COVID-19 & others) Research N/A30/03/2020 PR, 14/05/2020 PR N/A Subsidiary UREkA Pharma recently joined a consortium dedicated to the development of novel peptides intended to block the fusion of COVID-19 and other viruses to the target cell. Immupharma is also investigating the potential of Lupuzor (unsuccessfully tested in SLE) to treat the hyperinflammation associated with COVID-19.. +10.3

Yes (1.5m£)
MedinCell (FR) - MEDCL Long-acting ivermectin Blockade of SARS-Cov-2 virus cell entry Inhibitor of Importin α/β-mediated Nuclear Import (SC) Research N/A06/04/2020 PRAntiviral Res. publication (external), Obsevational Study Preprint (external) Long-acting antimalarial program oportunistically repurposed for COVID-19, based on an academic paper showing the in vitro activity of ivermectin. Ivermectin is an FDA-approved for parasitic infections. Preprint out with a retrospective obervational study. Other preprint out questioning any possible therapeutic window (even though MedinCell approach is more oriented towards exposure & prophylaxis). +19.4

Yes (15.6m€)
Evotec (DE) - EVT Multiple activities Multiple R&D services N/A Research N/A26/03/2020 earnings call, 30/04/2020 corp. update N/A Evotec is involved in a number of activities in the global fight against COVID-19, which include: * the NIH-led initiative Accelerating COVID-19 Therapeutic Interventions and Vaccines ("ACTIV"), a public-private partnership; * the "COVID R&D", the global crowdsourcing initiative among top pharmaceutical company R&D leaders aimed at facilitating therapies and vaccines against COVID-19 (Evotec to sponsor the PC repurposing group to channel candidate molecules from consortium members or external sources to COVID R&D); * the support to some local hospitals to assist them with analysing their tests; * the POC research project for N4 Pharma's novel delivery system; * the support of Ology Bio with screening and analytical characterisation services for antibodies against SARS-CoV-2 via Just - Evotec +11.3

(Unrelated to COVID)
Mithra (BE) - MITRA Estretrol E4 ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection Natural estrogen Research (pot. Phase 2 late 2020) N/A25/05/2020 PR N/A Research program initiated in May 2020 on the potential beneficial impact of Estetrol in the treatment of Covid-19. A Phase II study should be conducted in late 2020 on both male and female patients infected with the virus. No convincing rationale provided, except that the "gender disparity [in deaths from COVID-19] is believed to be biological differences in the immune system", and the fact that estrogen downregulates ACE2 (which could also cause safety issues by creating an imbalance in the RAAS system). -13.4

(Unrelated to COVID)
Yes (65m€)
Cyxone (SE) - CYXO CYXO-KASK-COVID ARDS/Pneumonia/Immune response linked to COVID-19/SARS-Cov-2 infection undisclosed Research N/A10/06/2020 PR N/A Collaboration signed with Dr kalev Kask to develop a new program for treating patients suffering from symptoms of Covid-19. Cyxone finds the collaboration regarding new therapeutic applications attractive from a business development perspective. According to the agreement, Cyxone will own all future IP rights and assume the costs for the development work. +106.2 (new entry) No
Avacta (UK) - AVCT Affimer Platform COVID-19/SARS-Cov-2 rapid test Affimers as reagents of an immunoassay Development started N/A08/04/2020 PR N/A Partnership with Cytivia to develop and manufacture an Affimer-based point-of-care rapid test intended for screening of large populations to diagnose the COVID-19 infection +458.2

Yes (53.8m£ in multiple operations)
N.B. The arrow direction relates to the last post update.

Conflict of interests: at the moment of initial publication (14/04/2020), the author of this post, Bertrand Delsuc, owns shares in some companies mentioned in the table (no significant ownership, none related to any COVID-19 program). The data in this post are no investment recommendations.

image credits: Centers for Disease Control and Prevention (CDC) / unsplash