​COVID-19 case numbers are soaring and health authorities are getting increasingly worried about coronavirus variants, yet investors are growing less optimistic about many of the companies that are trying to develop treatments for the infection.

Many of the stocks that skyrocketed in 2020 -- including Tiziana Life Sciences Plc and Sorrento Therapeutics Inc. -- have fallen from their highs amid mounting expectations that the pandemic can be suppressed through vaccination. At the same time, some biotechs such as France’s Abivax SA have abandoned trials for drugs to fight infection with the coronavirus.

“If share prices of these companies implicitly assume that many, many people will be treated every year then they’re clearly overvalued,” said Adam Barker, an analyst at Shore Capital.

To be sure, the surge in coronavirus cases in countries such as India shows that treatments will still be needed as new strains of the disease emerge that can escape first-generation immunity. It’s just turning out to be harder to develop effective drugs than the most optimistic investors expected.

There are hundreds of drugs in development for COVID-19. Ten have been approved for emergency use by the U.S. Food & Drug Administration and only one, Gilead Sciences Inc.’s remdesivir antiviral, has won full approval.

That drug hasn’t been shown to reduce deaths from the virus, only to reduce the time needed to recover from it. A surge in sales of the product hasn’t helped the stock price: Gilead is up about 8 per cent since winning regulatory backing, underperforming an index of health-care stocks in the U.S.

Here’s a roundup of some of the COVID treatment stocks and where they stand more than a year on from the onset of the pandemic.

Tiziana Life Sciences Plc: -68 per cent from 2020 peak

Tiziana peaked in July when it sought a U.S. patent for its monoclonal antibody TZLS-501 in the treatment of COVID-19. The company launched its first clinical trial for the nasally administered treatment in November, with positive results reported at the start of February. It’s planning to begin larger trials on both outpatients and inpatients, said Howard Weiner, a scientific advisor for Tiziana. The shares have fallen 7.1 per cent this year.

Humanigen Inc.: -47 per cent from 2020 peak

Humanigen shares soared 618 per cent last year. Preliminary data last month from a late-stage trial showed that its lenzilumab drug increased survival of hospitalized patients without the need for ventilation. The company has shared the results with regulators worldwide and plans to apply for approval, Chief Executive Officer Cameron Durrant said by email. Analysts are still bullish: Six of the seven tracked by Bloomberg have buy or equivalent ratings on the stock.

Vir Biotechnology Inc.: -42 per cent from Jan. 2021 peak

Vir more than doubled last year and then surged anew early in 2021, causing losses for short sellers who had bet on the stock declining. Late-stage trial data subsequently showed the U.S. company’s VIR-7831 antibody, developed with GlaxoSmithKline Plc, led to a significant reduction of hospitalization and death. The companies applied for emergency-use clearance in the U.S. on March 26 and the drug is being reviewed by the European Union. The stock has pulled back to below US$49 as a Reddit-fueled frenzy in the most-shorted names cooled down. Analysts are mostly bullish on Vir, though their price targets range from US$33 to US$135, reflecting a wide range of possible outcomes. JPMorgan Chase & Co., the lone bear on the stock, says, “Valuation is a concern.”

Synairgen Plc: -40 per cent from 2020 peak

Synairgen’s 2,520 per cent gain last year was the biggest in the FTSE AIM All Share Index. In a clinical trial, SNG001, the company’s formulation of the human protein interferon beta, cut the risk of patients developing the worst symptoms of COVID-19. Now Synairgen has begun dosing in a late-stage trial of hospitalized patients and begun a mid-stage study in people not requiring hospitalization.

“Synairgen has shown early proof-of-concept data that suggest their medicine could provide a profound benefit to patients, potentially materially better than anything we have seen to date from some of the higher-profile companies,” said David Pinniger, lead manager of the Polar Capital Biotechnology Fund, who owns the stock.

Sorrento Therapeutics Inc.: -55 per cent from 2020 peak

The shares surged in May 2020 and again in August after the San Diego-based company said it discovered an antibody that could protect against COVID-19, only to have skeptical short sellers pile in to bet against it. It still ended 2020 up more than 100 per cent. Early-stage data from a handful of COVID-19 patients sent the shares higher again in January, though they have since dropped off. The company said last week it plans a bigger study. Sorrento is studying experimental treatments for other illnesses as well that may pay off, said Raghuram Selvaraju, an analyst at H.C. Wainwright & Co. “Sorrento’s antibody pipeline is broad and diverse, while also rapidly advancing in maturity,” he wrote in a report this week, reiterating his buy recommendation.

Celltrion Inc.: -32 per cent from 2020 peak

Celltrion shares more than doubled last year. The company received conditional approval from South Korea in February for its antibody treatment, regdanvimab, in high-risk patients with mild to moderate COVID-19 symptoms. The EU regulator in March said the product can be used in some high-risk adult patients, though data from an ongoing study wasn’t robust enough to reach a firm conclusion on the medicine’s benefits. Celltrion is working on its Phase 3 clinical trial on about 1,300 people and plans to get results by the end of June, a spokesman said.

Abivax SA: -37 per cent from Jan. 2021 peak

The French drugmaker’s stock jumped 53 per cent last year. In March the company ended trials of its anti-inflammatory drug ABX464 in COVID-19 patients after it showed no signs of efficacy. The shares fell the most in almost five years, despite analysts stressing the drug’s potential in other uses such as for ulcerative colitis and inflammatory bowel disease. The six analysts tracked by Bloomberg who cover Abivax see about 65 per cent upside, on average, for the stock.

BerGenBio ASA: -37 per cent from 2020 peak

The Norwegian company’s stock almost doubled through mid-May last year, only to give up half the gains after the U.K. pulled funding in July for a study in which its bemcentinib was the lead drug candidate to be tested. Short interest has climbed as investors await data from a mid-stage trial in hospitalized COVID-19 patients. Preliminary data released this month showed the drug was well-tolerated with no safety issues, while more detailed data is expected in May.

--With assistance from Youkyung Lee and Cristin Flanagan.