Could AI avert a future coronavirus pandemic?

Could AI prevent future pandemics by developing an armoury of drugs that work against all coronaviruses?

This is a question that a consortium of European pharma companies hopes to answer as it aims to rapidly develop new therapies to combat the pandemic.

The Corona Accelerated R&D in Europe (CARE) has been hastily set up by Europe’s Innovative Medicines Initiative (IMI), focusing on tackling the pandemic that has wreaked so much havoc across the world this year.

The consortium aims to rapidly develop drugs to fight SARS-CoV-2 and find virus neutralising antibodies.

But also included in the 77.7 million euro project funded by European Union cash and European pharma companies is a work stream that aims to find drugs that work against coronavirus strains that may emerge in the future.

The UK-based artificial intelligence (AI) drug discovery firm Exscientia is heavily involved in this project and is using its technology to screen existing small molecules to see if they could be used against the coronavirus class that causes diseases such as SARS, MERS and COVID-19.

Exscientia is finishing off work already done on the SARS-CoV-2 virus to identify the targets that could be used – but chief operating officer Dave Hallett told pharmaphorum in an interview that the likely lines of attack are already well known.

The trick is to look for proteins that are used across all coronavirus types and tend not to vary much from one virus species to another.

Hallett said that the targets being explored are the proteins involved in viral replication – the protease, the RNA polymerase, the papain-lie protease and elements of the “Spike” protein that allows the virus to infect cells.

He said: “If you could find a small molecule now that had SARS, MERS, and COVID-19 activity there is a reasonable chance it could have activity against another beta-coronavirus in the future.”

The work will involve using AI to screen a library of 12,500 drugs held by Scripps Research to identify small molecules that could be active against the virus class.

All of the drugs in the library have previously been used in humans, which means their side effects are better known, hastening development.

“If we can find any drugs that have gone into human beings if one of those has activity against COVID-19 proteins those would make it more rapidly through clinical trials.”

CARE is a five-year project funded by the cash contributions from the EU, 11 European Federation of Pharmaceutical Industries and Associations (EFPIA) companies, and three IMI partners.

Companies include Johnson & Johnson’s Janssen unit, Takeda and Boehringer Ingelheim.

Hallett noted that the project is an example of how European countries and organisations can work together, something that he hopes will continue as the UK heads for Brexit.

“It’s a reflection of what the IMI was set up to do. It’s shame we are leaving as it’s a good example of what Europe can do when it comes together.”

“We can move forward quickly with this, fingers crossed.”

Could AI avert a future coronavirus pandemic?

J&J snags novel autoimmune project, and Momenta

The $6.5bn price – biopharma’s biggest buyout of the year so far – shows how competitive the anti-FcRn space has become.

The substantial potential seen in projects that target neonatal Fc receptor (FcRn) has triggered much dealmaking over the past few years. Johnson & Johnson’s $6.5bn takeout of Momenta represents the biggest play to date.

J&J is getting the whole of Momenta, but the deal is mostly about nipocalimab, which delivered impressive proof-of-concept data earlier this year; that could well have been the trigger for talks. And, while the 70% premium looks generous, intense competition for these assets already has some in the sellside asking whether this will be enough to seal the deal.

Momenta shares opened a touch below the $52.50 that J&J has agreed to pay, suggesting that the market does not see another bidder entering. It is hard to believe that this was not already a competitive sale process, and Momenta’s bankers have surely been busy shopping the company around. 

Truist analysts (formerly SunTrust Robinson) asked this morning whether J&J “may have underplayed”; it is worth noting that they are defending a price target of $53, considerably higher than most other banks. Takeover battles are rare, particularly in the wake of an agreed bid such as this one, but it is also true that there are few other unencumbered anti-FcRn assets out there.

FcRn targeted projects: the progress so far (in myasthenia gravis)
Project	2026e sales	Company	Next steps
Efgartigimod	$2bn	Argenx	US filing due by year end
Rozanolixizumab	$319m	UCB	Ph3 readout expected H1 2021
Nipocalimab	$166m	J&J (Momenta)	Momenta planned to start ph3 by YE 2020
IMVT-1401	$597m	Immunovant/Harbour Biomed	Ph 2a readout Q3 2020
ALXN1830	$13m	Alexion (Syntimmune)	Paused owing to Covid-19, to restart 2021, SC formulation prioritised
ABY-039	–	Affibody	Project terminated in Jun 2020 on tolerability issues, Alexion handed back rights.
Source: EvaluatePharma, company statements.

The target has attracted much attention because of its broad applicability across a range of autoimmune diseases, many of which have few if any treatment options. By inhibiting FcRn these projects are thought to be able to control the recycling of IgG and reduce the activation of complement, which is believed to drive many conditions.

Efgartigimod is the most advanced asset in biopharma’s anti-FcRn pipeline. With a market cap of $11bn and a fiercely independent chief executive, however, Argenx would probably prove too pricey for most buyers. As a large mid-cap UCB is also planning to go it alone, though rozanolixizumab is also considered the weakest project.

Alexion snapped up Syntimmune back in 2018, for what now looks like a good value $400m up front; a deal over an Affibody candidate ended up bust earlier this year. And, with Momenta now gone, this leaves Immunovant, shares in which duly jumped 13% this morning. Data due any day now on IMVT-1401 now become even more interesting. 

Interestingly Argenx shares also opened higher this morning, as a big pharma endorsement presumably outweighed the threat of another deep-pocketed competitor, alongside Alexion, arriving on the scene.

A fitting end?

J&J’s plans for nipocalimab will also be eagerly awaited. A press release contained few details but mentioned huge swathes of disease areas that might be investigated, from maternal-foetal disorders, neuro-inflammatory disorders to rheumatology, dermatology and autoimmune haematology. 

And of course Momenta was about more than nipocalimab. M254, a hypersialylated IgG, will deliver results in idiopathic thrombocytopenic purpura shortly. But the decision a couple of years ago to exit biosimilars now looks well judged. After spending years trying to get its Copaxone generic, Glatopa, to market, Momenta threw in the towel on the copycat business in late 2018, a defeat that arguably had more to do with the impenetrable US biologicals market than with its failings.

Long-term investors will be happy to dismiss that history – before today the stock had never closed above $40, in over 16 years on the market.

The acquisition also ranks as the largest biopharma buyout so far this year, knocking Gilead’s $4.9bn takeout of FortySeven off the top spot. The fact that deals are getting done, despite the pandemic being far from over, will also please the sector and its followers.

https://www.evaluate.com/vantage/articles/news/deals/jj-snags-novel-autoimmune-project-and-momenta

Gilead’s Filgotinib setback vindicates Abbvie’s opt-out

A shock US rejection delays approval by at least two years and makes Abbvie, which had given up rights five years ago, look smart.

Galapagos had looked like a dealmaking genius when it partnered and then repartnered filgotinib, but after market close yesterday reality bit. The Jak1 inhibitor has been handed a US complete response letter that could delay its approval for rheumatoid arthritis until 2022.

The unexpected setback, caused by toxicity concerns, will come as a rude awakening to those who had long seen filgotinib as the safest of the Jaks. And it will compound growing concerns over filgotinib’s late market entry, which had already caused the project’s forecasts to be whittled away, as consensus data from EvaluatePharma reveal.

Little wonder that shares in Galapagos and Gilead, to which filgotinib was licensed in 2015, came off this morning, to the tune of 27% and 3% respectively. Filgotinib is a key part of both companies’ growth plans, its NPV accounting for a respective 54% and 5% of the two groups’ market caps, according to EvaluatePharma calculations of sellside consensus numbers.

Instead, it is Abbvie that today looks like the business development genius. Abbvie had five years ago controversially given up rights to opt in to filgotinib, preferring instead to focus on its own Jak1 inhibitor, which was launched last year as Rinvoq (For AbbVie filgotinib becomes no-go-tinib, September 25, 2015).

In December 2015 Gilead picked up filgotinib for $300m up front, plus a $475m equity investment, with an obligation on the junior party to fund just 20% of phase III costs. This gave Galapagos an even better deal than it would have had with Abbvie.

Rinvoq wins?

But today Rinvoq is winning the race for rheumatoid arthritis market share – among the Jaks at least – notwithstanding its own toxicity problems. It was launched with a label warning for thrombosis, similar to that for the older Jak inhibitors Xeljanz and Olumiant.

But in this market coming first counts for a lot. In a scathing note to clients this morning Wolfe Research’s Tim Anderson wrote that even before yesterday’s setback filgotinib was going to struggle commercially, being “a late-entrant into a crowded category, dominated by deep-pocketed big pharma companies who know the space much better than Gilead”.

Such growing concerns are reflected in historic sellside consensus, as compiled by EvaluatePharma, which shows that 2024 US sales forecasts have fallen from $1.5bn two years ago to $818m today.

Now the task of competing has become even harder. The complete response letter cites possible impact of filgotinib’s 200mg dose on sperm parameters, and the FDA wants to see data from the Manta and Manta-Ray trials, due in 2021, before deciding on approvability.

Manta and Manta-Ray had been initiated to investigate the possibility of filgotinib having testicular toxicity, an issue that came up some years ago in a rat study.

Anyone wondering whether the problems end there would do well to consider why the FDA decided against approving just the 100mg dose, however uncompetitive its efficacy might have been. The fact that the agency did not hints at broader concerns it might have over filgotinib’s risk/benefit profile.

Outside the US the news for Gilead/Galapagos is better as filgotinib looks soon to be approved in Japan and the EU, where despite rumours to the contrary the CHMP delivered a positive opinion last month. But the US, where filgotinib will be Gilead’s sole responsibility, is clearly where the big money is.

So pressing was the need for filgotinib to get to market quickly that Gilead had filed it with a priority review voucher that it had bought from Ultragenyx for $81m. This has enabled the FDA to say “no” four months sooner than it might otherwise have done.

https://www.evaluate.com/vantage/articles/news/corporate-strategy/filgotinib-setback-vindicates-abbvies-opt-out

Bangladesh ready to trial Indian COVID-19 vaccines

Bangladesh is ready to hold trials of potential COVID-19 vaccines developed by India and will receive early supplies of any successful candidate, officials said on Wednesday, as a Chinese firm continued to await assent for its trial request.

New Delhi considers its eastern neighbour Bangladesh a strategic ally and is wary of Beijing’s rising influence there.

Indian Prime Minister Narendra Modi sent his foreign secretary to Bangladesh’s capital Dhaka on Tuesday on a two-day visit to hold meetings with Prime Minister Sheikh Hasina and officials.

“Bangladesh is ready to collaborate in the development of a COVID vaccine, including its trial, and looks forward to early affordable availability of the vaccine when it is ready,” its foreign ministry said in a statement.

The release followed a meeting of the foreign secretary and his Indian counterpart Harsh Vardhan Shringla, during which Shringla had discussed India’s economies of scale in vaccine manufacturing with Bangladeshi officials, the statement said.

“They (India) positively responded, saying that they are developing vaccines not only for themselves but also for others,” Bangladesh’s Foreign Secretary Masud Bin Momen told reporters after the meeting.

“It will be made available for Bangladesh in the primary stage.”

India is home to the world’s biggest vaccine making company, the Serum Institute of India, and is currently holding trials for three potential COVID-19 vaccines, including one licensed to AstraZeneca Plc by Oxford University.

The state medical research agency of Bangladesh, which has reported 285,091 coronavirus infections and 3,781 deaths, approved a third-phase trial of a potential COVID-19 vaccine developed by China’s Sinovac Biotech Ltd last month.

However, final approval from the government is still pending.

https://www.marketscreener.com/quote/stock/SINOVAC-BIOTECH-LTD-5714593/news/Sinovac-Biotech-Bangladesh-ready-to-trial-Indian-COVID-19-vaccines-31144781/

Mexico exploring phase 3 trials of Russian coronavirus vaccine

Mexico told Moscow on Wednesday it would like to carry out phase 3 testing of Russia’s coronavirus vaccine, as part of the Latin American country’s intensifying efforts to secure early supplies of an effective medicine to control the pandemic.

After a meeting with Russia’s ambassador to Mexico, Viktor Koronelli, Foreign Minister Marcelo Ebrard said on Twitter he had expressed interest in carrying out large scale human trials “to have the vaccine as soon as possible in Mexico.”

Russia has already produced the first batch of its new vaccine, giving approval before trials that would normally involve thousands of participants. Such phase 3 trials are usually considered essential precursors for a vaccine to secure regulatory approval.

The race to produce a vaccine has become a contest for influence and prestige among major powers, while developing economies are trying to ensure a fair distribution of the medicines.

Russia’s vaccine, named ‘Sputnik V’ in homage to the world’s first satellite launched by the Soviet Union during the Cold War, is the first to go into production and is to be rolled out by the end of this month.

Russian President Vladimir Putin has assured the public that it is safe.

His Mexican counterpart Andres Manuel Lopez Obrador said earlier this week he would volunteer to be among the first to try the Russian vaccine if it proved effective.

Mexico has already agreed to help manufacture a vaccine candidate being developed by Britain’s AstraZeneca and Oxford University to supply the Latin American market.

It is also preparing to carry out late-stage trials for U.S. company Johnson & Johnson and two Chinese companies.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-Mexico-exploring-phase-3-trials-of-Russian-coronavirus-vaccine-31146771/