What BioNTech did subsequent: the plan for a revolution in most cancers care


Uğur Şahin arrives at BioNTech’s headquarters within the German metropolis of Mainz on the identical battered bicycle he has been using for 20 years. Developing the best-selling Covid-19 vaccine could have remodeled BioNTech’s founders into billionaires, however the chief govt of the biotech enterprise has resisted making adjustments in his private life.

Şahin and his spouse, chief medical officer Özlem Türeci, arrange BioNTech in 2008 to create a toolbox to remodel the therapy of most cancers. Since discovering fame, their imaginative and prescient has not shifted. When practising as docs, the pair had grow to be annoyed on the hole between the most cancers medicine out there on the wards — and what they believed was scientifically potential.

So, whereas the mRNA vaccine they developed with the American prescribed drugs firm Pfizer has saved hundreds of thousands of lives and introduced economies around the globe again to life, it was additionally, in some methods, a aspect hustle. BioNTech “is a cancer company that was able to drop everything they were doing to create a Covid vaccine,” says Akash Tewari, an analyst at Jefferies.

The resolution to take action has introduced an unprecedented windfall of money to the corporate, which is now sitting on belongings of €19bn, with billions extra in income anticipated. That quantity equates to “a lifetime of funding”, says Suzanne van Voorthuizen, co-head of life sciences securities at Dutch financial institution Kempen & Co.

Lab technicians work on producing CAR-T cells and RNA within the laboratory for French biopharmaceutical firm Cellectis in Paris final September © Thomas Coex/AFP/Getty Images

While some billionaires use their wealth to purchase newspapers or fund extraterrestrial adventures, Şahin and Türeci will use theirs to gasoline their bold — although nonetheless nascent — plans in oncology. They are doubling down on a hope that Şahin admits as soon as seemed like science fiction: to have the ability to tailor medicine to every affected person’s most cancers.

The firm not too long ago took steps in the proper route with two early stage trials exhibiting promising information, one in pancreatic most cancers and the opposite concentrating on strong tumours together with ovarian and testicular most cancers.

Success would imply a brand new journey: reimagining the entire pharmaceutical business.

“We had this idea to develop technologies dedicated to really saving every single individual patient,” says Şahin. “Because every patient is different, and you can’t just take something off the shelf.”

The Covid money

Şahin wheels his bike across the perimeter of an enormous gap on the plot of the corporate’s web site — the inspiration for a brand new 20,000 sq. foot constructing. Across from his workplace, a three-storey short-term lab in portacabins has popped as much as press on with the mission immediately: this yr analysis and growth spending at BioNTech is doubling to €1.5bn.

Dropping his helmet in his workplace and donning a white coat, Şahin heads to the lab. Inside, a machine synthesises the DNA templates used to create messengerRNA, the expertise BioNTech has helped to pioneer.

The mRNA acts as a set of directions to cells, telling them to construct sure proteins. The response to the pandemic proved for the primary time that the expertise could possibly be used to create a extremely efficient vaccine: mRNA was deployed in a vaccine to assist the immune system recognise and struggle intruders such because the coronavirus Sars CoV-2. Next, BioNTech desires to make use of the code to immediate the physique’s defences to sort out a tumour.

Yet, in contrast to its American rival Moderna, which is targeted on tips on how to deploy mRNA throughout a variety of infectious illnesses and different situations, BioNTech desires to make use of mRNA to sort out most cancers, working together with different therapies. Şahin and Türeci imagine the most effective hopes of a remedy will come from combining totally different remedies, together with cell therapies, antibodies and different methods of modulating the immune system.

Uğur Şahin: ‘We had this idea to develop technologies dedicated to really saving every single individual patient’
Uğur Şahin: ‘We had this idea to develop technologies dedicated to really saving every single individual patient’ © Ben Kilb/FT

Before the pandemic, the corporate was somewhat recognized participant within the $1.2tn world prescribed drugs market that’s dominated by long-established firms pursuing many illness areas without delay. In its 2019 preliminary public providing, BioNTech struggled to get traders excited, elevating simply $150mn; two years later it had grow to be probably the most promising biotech in Europe.

Matthias Kromayer, a managing associate at MiG Capital, who was a founding investor in BioNTech, says when he invested he didn’t even imagine within the potential of mRNA. He gave the infant BioNTech cash as a result of the founders appeared to know how expertise would change healthcare, he says. “BioNTech isn’t just a biotech company. It is a multi-tech company and has been from the beginning . . . Ugur is always thinking 10 years ahead.”

In April, BioNTech unveiled outcomes of a research that mixed mRNA with CAR-T-cell remedy to reprogramme a affected person’s immune system. CAR-T is a posh therapy that entails accumulating and modifying a affected person’s immune cells to struggle their most cancers. So far, it has solely labored in blood cancers. But BioNTech scientists created an mRNA booster that expanded the variety of immune cells and improved their means to kill a strong tumour, making it helpful in a far bigger vary of cancers.

Brad Loncar, a biotech investor who runs a fund targeted on most cancers, declared it “borderline revolutionary”. “It is so interesting that it has the entire field rethinking how to go after solid tumours,” he says.

Diagram showing how cancer vaccines can be engineered to treat individual patients

BioNTech’s technique is to put money into many various applied sciences without delay. Şahin makes use of the analogy of a smartphone that turns into extra helpful as you uncover its many features. “You understand it is not just a smartphone, it is a calculator, it allows you to do anything,” he stated. “Based on the powerful platforms that we are developing, we believe that we will be able to provide a lot of different solutions for many diseases.”

Broadly talking, the BioNTech founders see themselves as engineers of the immune system. Beyond most cancers and infectious illnesses, the place the corporate continues to associate with Pfizer on vaccines, in addition they plan to sort out autoimmune situations and regenerative drugs, which restores broken or diseased cells. In complete, the corporate is already operating 19 early stage trials and 12 pre-clinical programmes.

Their newly bulging pockets allow such largesse, says one healthcare banker. A extra cash-strapped firm must be extra selective and threat “throwing a great technology in the bin”. At the tip of March, BioNTech’s belongings had been greater than €19bn, surpassing even Moderna’s €16bn, and greater than half that of enormous European pharma firms GlaxoSmithKline, AstraZeneca and Novartis.

The BioNtech headquarters in Mainz in Germany. The company’s strategy is to invest in many different technologies at once
The BioNTech headquarters in Mainz in Germany. The firm’s technique is to put money into many various applied sciences without delay © Ben Kilb/FT

Cancer trials are costly, particularly if an organization has to first purchase the drug it needs to mix with its therapy. And personalised merchandise resembling CAR-T have confirmed troublesome to market in a worldwide healthcare system that’s extra aware of shopping for medicine off the shelf resembling client items.

With valuations of biotech firms dropping this yr, Gareth Powell, a healthcare fund supervisor at Polar Capital, says BioNTech is fortunate it could fund so many programmes. “If they didn’t have the Covid cash . . . I would imagine they would be under severe pressure,” he says. “The capital markets just wouldn’t be there for them to do this stuff.” 

‘Money doesn’t develop on timber’

Bryan Garnier & Co was a part of a staff of banks that helped take first Moderna after which BioNTech, public. Pierre Kiecolt-Wahl, co-head of fairness capital markets on the French financial institution, says Moderna took a extra incremental method than BioNTech’s, focusing first on infectious illnesses, the place it hoped to indicate indicators of success rapidly that would persuade traders to place in additional funds.

“Moderna knew money doesn’t grow on trees,” he says. By distinction, he says Şahin and Türeci had been extra assured that they’d information to struggle most cancers.

But although it now has substantial monetary sources, long-term success isn’t assured. Loncar says it could but prove that mRNA doesn’t actually work for most cancers. “There’s a non-zero per cent chance that mRNA may completely strike out in cancer,” he says. “If that happens, BioNTech is going to feel it a lot harder than Moderna will.”

Oncology is way trickier than creating vaccines — Tewari, the Jefferies analyst, describes it as “scientifically byzantine” — and it’s a hypercompetitive discipline, with nearly each main pharmaceutical firm scouring for remedies for a similar situations.

Bar chart of Total current assets (including cash, receivables, inventories) at end of March 2022 showing BioNTech secures a 'lifetime of funding' with Covid jabs

BioNTech’s most superior medical oncology programme is for most cancers vaccines. Unlike common vaccines, they don’t stop the recipient from growing most cancers, however are used as remedies to immediate the immune system to destroy mutated cells. In section 2 trials, it has two FixVac programmes, the place the vaccines aren’t personalised, and two the place they’re.

Hopes for creating most cancers vaccines have been dashed many occasions earlier than. “It is a concept that has been around for decades. But there has been failure, after failure, after failure,” says Loncar.

He says one downside could possibly be that therapies are being deployed too late. New therapies are normally tried first in sufferers who haven’t responded to earlier medicine and normally have later stage most cancers, however he believes they could work higher at an earlier stage, when the affected person’s immune system is extra strong.

Şahin counters that BioNTech has overcome numerous “critical hurdles” and that its early information exhibits its mRNA most cancers vaccines are eliciting immune responses a number of hundred occasions stronger than had been beforehand reported for standard most cancers vaccines.

A biologist at the French-Austrian biotech firm Valneva enters a laboratory to work on an inactivated whole-virus vaccine against coronavirus in Vienna, Austria, last December
A biologist on the French-Austrian biotech agency Valneva enters a laboratory to work on an inactivated whole-virus vaccine in opposition to coronavirus in Vienna, Austria, final December © Lisi Niesner/Reuters

The firm can be doing trials in earlier stage cancers, and is especially desirous about giving the vaccines simply after sufferers have had surgical procedure to take away the first tumour. In a section 1 trial introduced this month, the corporate confirmed constructive outcomes treating pancreatic most cancers sufferers shortly after surgical procedure.

But in addition to the scientific uncertainty, BioNTech will face sensible challenges because it tries to disrupt the pharmaceutical enterprise. The firm must push regulators to adapt to individualised therapies that break the mould of standard medical trials. While such trials normally take a number of years and result in an authorized product that by no means adjustments, the founders need to have the ability to replace their medicines — like an iPhone — as new information improves algorithms that predict the easiest way to focus on a tumour.

Türeci says the corporate has to take the “smallest steps” with “conservative” regulators each time they enter new territory. “The problem with the way medicines are developed is that, at that time when you have something you can approve for patients and bring it to the market, the technology is already outdated [by] several years,” she says.

The ‘smallest steps’

While BioNTech’s has no have to beg traders for extra capital, the corporate will nonetheless need to navigate expectations of shareholders who purchased it as a Covid inventory. Shares in BioNTech have fallen by about 20 per cent prior to now yr, after some traders bought in anticipation that gross sales of the Covid vaccine would gradual. But the inventory continues to be up greater than fourfold since March 2020, when the corporate first introduced it was growing a shot with Pfizer.

Loncar, the cancer-specialist investor, doesn’t personal BioNTech primarily as a result of it nonetheless trades as a Covid inventory. He believes shareholders could also be in for a shock. “Investors have been really spoiled by how quickly the Covid-19 vaccines succeeded and how well they did. That’s not normally how drug development goes,” he says. “One thing I worry about is they have a shareholder base today that expects them to succeed in non-Covid things tomorrow.”

Şahin tries to be sanguine concerning the firm’s inventory — he says he appears the value up about as soon as per week, far much less usually than he checks medical journal websites. And he stresses that the corporate has at all times been clear with traders about its true imaginative and prescient: “We can’t guarantee to them what is going to happen in the next Covid season. This is more dependent on what’s happening in the world and how the virus is evolving, and less dependent on our competencies.”

Still he was stunned not too long ago when the share worth rose as traders anticipated the corporate would create a vaccine for monkeypox. (BioNTech has not began work on a jab for the spreading illness. Şahin says they’re “preparing ourselves to be prepared” to take action, but it surely doesn’t appear to be a worldwide problem but.)

Some traders are asking whether or not BioNTech can deal with fairly a lot money — and tackle so many challenges without delay.

(L-R) President of Ghana Nana Akufo-Addo, German minister of economic cooperation and development Svenja Schulze, director of the Africa Centres for Disease Control and Prevention John Nkengasong, WHO director general Tedros Adhanom Ghebreyesus, Rwanda’s president Paul Kagame, BioNTech CEO Ugur Sahin, president of Senegal and African Union Macky Sall during a statement by Tedros at BioNTech’s manufacturing site at  in Marburg, western Germany, in February
(L-R) President of Ghana Nana Akufo-Addo, German minister of financial co-operation and growth Svenja Schulze, director of the Africa Centres for Disease Control and Prevention John Nkengasong, WHO director-general Tedros Adhanom Ghebreyesus, Rwanda’s president Paul Kagame, BioNTech CEO Ugur Sahin, president of Senegal and African Union Macky Sall throughout a press release by Tedros at BioNTech’s manufacturing web site in Marburg, western Germany, in February © Andre Pain/AFP/Getty Images

While the corporate has determined to make use of the overwhelming majority of its vaccine proceeds for inside funding, with simply a few small bolt-on acquisitions, it did announce plans to return nearly €2bn to shareholders in a buyback and dividend. This additionally divided shareholder opinion, as a result of it’s so uncommon for a biotech with many programmes in early stage growth to cough up money. “It was a terrible idea,” says Powell at Polar Capital. “It’s such a waste of money.” 

But analysts say that the majority long-term traders belief the founders who delivered the Covid vaccine at such scale and velocity. Van Voorthuizen at Kempen says they’re notably “diligent” about structuring their trials in order that they offer strong solutions to particular questions. “They will stop [a trial] if it doesn’t work. They are not depending on one or other programmes to make or break the company,” she says.

The healthcare banker believes BioNTech is “by far the most exciting biotech in Europe”, including that there aren’t any founders extra inspirational than Şahin and Türeci. “They are so insanely smart and they work so damn hard,” he says.

Türeci describes how Şahin can suck up data, quickly studying dozens of papers on a brand new situation. “It’s sort of something like machine learning what he does,” she jokes. “In a weekend, the entire history of science on this specific topic.” 

Governments from around the globe are calling for recommendation for birthing their very own variations of BioNTech, Türeci says. But, simply as the corporate stunned the world in 2020 by navigating the uncharted waters of mRNA vaccine growth, Türeci says they’re as soon as once more heading into “unknown territory”. And this time, success isn’t more likely to occur at lightspeed.

Source: www.ft.com