It is 9 pm, 27 October. The marketing team members were the last one to leave the Tevogen Bio headquarters in Warren, New Jersey, and right now, Dr Ryan Saadi, the founder chair and CEO of the biotech company is the only one working at the sprawling, empty office. Even though he lives just five kilometres away, Dr Saadi is unlikely to leave before 3am.

On Sunday, the company will release an important statement to the press concerning Tevogen 489, their flagship product for elderly and high risk Covid-19 patients. Tevogen 489 is unlike any other Covid-19 treatment out there. It uses genetically unmodified T cells to target the Covid-19 virus genome, specifically the least likely to mutate parts of the virus, ensuring that the therapy works on every possible variant of the virus.

“I fear this will be a rough winter and we will do everything possible to bring Tevogen 489 to patients this winter,” says Dr Saadi. The clinical trial has already established it is safe and Tevogen Bio is exploring all options for speedy development and manufacturing of the product.

Tevogen Bio was founded as recently as June 2020 by Dr Saadi, after he spent two decades working for big pharma companies, and he is its majority share owner. None of Tevogen Bio’s products are actually commercially available as yet, and still the company is valued at a whopping $4.25 billion, despite resisting the temptation to go public till now.

Part of the answer lies in Tevogen Bio’s ability to create safe T cells. T cells are a natural part of our body’s immune system and the only one that can fight the viruses even after it has infected our cells. Although T cell therapy is already used to treat different disease conditions, it is both expensive and of limited use, since the therapy itself can become quite toxic.

It took around 18 months for Tevogen 489 to complete proof of concept clinical trials, when typically, pharmaceutical products take anywhere between 7-10 years. Moreover, developing a pharmaceutical product typically costs around $2.6 billion, and in Dr Saadi’s words – Tevogen 489 costs a fraction of that. In fact, one of the three patents (with eight other patents pending) that Dr Saadi holds – which he assigned to Tevogen Bio – is on “bringing down the manufacturing cost.”

Tevogen 489 is also off-the-shelf, meaning a patient will no longer require a specialised hospital to receive therapy and any doctor can prescribe it.

“I had to find a way to apply science to bring down the costs of the medicine, that was one thing. Also, I could not take 10 to 15 years, I had to be quick. By having done that, our products are going to get a price point that any individual will be able to afford,” he says.

From Kushtia to Big Pharma

Both Tevogen Bio and its founder Dr Saadi are right now one of the most exciting and talked-about developments in the US biotech industry. The company promises to not just make products that are affordable, targeted and yet profitable, but also address “health inequality” in the US and around the world in the long run.

Addressing health inequality however is not what big pharma is usually known for. In fact, often, they are criticised for being “exploitative”. So what motivated Dr Saadi – a big pharma executive for two decades – to take on this task?

For Dr Saadi, part of the motivation stems from where he comes from. In 1971, Saadi was only eight years old when the Bangladesh Independence War broke out, and he experienced first-hand the ravages of the war.

“I lost 11 of my uncles in the war – almost my entire maternal grandfather’s family. And I was right in the middle of it. They actually shot at me twice,” he says.

Dr Saadi spent his early childhood in Kushtia, in the midst of poverty and destruction left behind by the war. The early years of Bangladesh – when the country was considered the poorest in the world and moniker’s such as “bottomless basket” regularly accompanied its description in the international media – left a lasting impression on Dr Saadi.

“I don’t know about others, but I was really taken by the words of Bangabandhu Sheikh Mujibur Rahman. My life experience would not be a reality if Sheikh Mujib did not inspire a nation to realise its strength. Most call current Bangladesh a miracle but I see foresightedness of a leader who instilled optimism in every single one of us,” he said.

Over the last two and a half decades, Dr Saadi has worked at big pharma companies such as Sanofi, Genzyme, Johnson & Johnson, CSL Behring, while also serving as a Special US Government Employee for Health and Human Services. While still working for big pharma, Dr Saadi studied at the Harvard Business School, an important phase of his life which would go a long way to not just setting up Tevogen Bio, but also to design manufacturing processes that dramatically bring down costs.

“It’s not like I am being humble but when I think of it, this is not supposed to be happening to me. The same man who spent his childhood in the then poorest country in the world ended up going to Yale and Harvard; ended up working in 51 countries and living in nine. The universe has been very kind to me,” he says.

Like the garment industry in Bangladesh

In just two years, Tevogen Bio has grown out of Dr Saadi’s study room to four different locations in the US, including an R&D Centre in Philadelphia, headed by Dr Neal Flomenberg, one of the leading experts on T Cells in the world.

Both Dr Saadi and Dr Flomenberg come from a background in oncology, the branch of medicine that deals with cancers, as do many others in the top brass, and the company was originally conceived to bring about “better, faster and cost efficient” treatments of cancer and other disease conditions that have “high unmet need”, meaning there is nothing meaningful readily available for its treatment, such as multiple sclerosis.

“I was never really satisfied with existing cancer treatments. Most keep patients alive for a few months at a very high cost. So, we wanted to develop better therapies,” says Dr Saadi. Tevogen Bio very quickly developed an oncology and neurology pipeline, and then Covid came along.

“We realised our approach should work on Covid-19”, he says.

So what is this approach?

CD8+ T-Lymphocytes, also known as Cytotoxic or Killer T Cells, represent one of nature’s most powerful weapons against disease. As Dr Flomenberg, also Chief Scientific Officer of Tevogen Bio, describes it: whenever we are infected with a virus, the way our bodies get rid of it is by expanding a group of cytotoxic T cells.

“Cytotoxic literally means capable of killing…Mother Nature basically says I have to kill these cells off. It’s like it goes about blowing up virus production factories,” says Dr Flomenberg, during a zoom meeting later in the day. All other treatments out there for the most part buy time by slowing the virus down, to try and tip the race between the virus and our immune system.

To date, these cells have not been harnessed to their full potential for clinical application beyond limited CAR-T options, which typically costs half a million dollars per patient and $1.5 million if you include total cost, and only a few medical institutions in the US (140 out of 6,000 hospitals) have the capacity to offer CAR-T.

Furthermore, the therapy itself can become quite toxic. The challenge for the Tevogen Bio team was to create safe T cells, and they invented a way to do it by not genetically modifying the T cells.

“Tevogen 489 is an allogeneic product, meaning it is passed on from one person to another, as opposed to autologous products, where the product is developed from the person’s own cell,” says Dr Flomenberg.

“We can basically make products for multiple people – from three to upwards – from a single donor. This basically allows us to spread the cost to multiple people,” he adds. Dr Flomenberg says in their early trials they deliberately kept the number of doses from a single donor low so as to stay “comfortable”, but are confident that with time and further testing the doses can be vastly expanded, “in a worst case scenario, we should be able to get more than 100 doses from a single donor.”

When Tevogen Bio shifted their focus to Covid, they realised there was no way they could actually overcome the mutational challenge of the virus by going after only the spike protein.

“Covid-19 is a mutation prone RNA virus, and we are already experiencing variants with worrisome immune escape potential – particularly to the spike region. So what Neal and I did was, we spent significant resources and time to identify the TVGN 489 targets across the entire viral genome, which are less likely to mutate under evolutionary pressure.”

“What we are doing with Tevogen 489 is we are jumping to the finish line. We’re taking cells from somebody who’s already had Covid, who has already successfully fought it off; we are enriching and expanding them in the lab, and giving people a product which is highly purified cells,” he says.

The other innovation Tevogen Bio has brought about is the ability to be target-specific.

“If you have five cells which developed cancer or an infection, it will only go and target those, and it will kill the cells, and it is done. It doesn’t interfere with the rest; and the body will replace killed cells with healthy ones,” says Dr Saadi.

Having spent two decades in big pharma Dr Saadi had experienced first-hand what it takes to develop a product, starting from the lab to the market. It’s expensive, time-consuming, and failure rates can be as high as 90%.

“People are very quick to say that all these big pharmaceutical companies just want to abuse and want to take advantage, but that’s not an accurate assessment,” he says.

“I am a big pharma executive. I spent my lifetime working in big pharmaceuticals.  So my first instinct was that we have to bring down the cost of drug development and manufacturing.”

For obvious reasons, Dr Saadi could not elaborate much further on the mechanisms behind bringing the costs but cheekily quipped “It is simple, right? Think about the garment industry in Bangladesh.”

And just like the garment industry, Tevogen Bio’s projections indicate it would be left with fairly large profit margins, despite the dramatic drop in prices offered. Tevogen’s projected business model, in his words, is slated to make it one of the most profitable biotechs in history.

An American gratitude

Part of Dr Saadi’s motivation has to do with where he comes from. The other part appears to be wanting to give back to his adopted country, the United States. Throughout his career as a medical professional and pharma executive, he has found the health inequality in the US confounding.

Despite the fact that the US health budget at $4 trillion is equivalent to the entire GDP of Germany, the US is just about the only country in the developed world where life expectancy has been in decline since the 1980s. While the cost of healthcare steadily goes up, outcomes steadily come down.

“There are many things in life which can be optional. If you want to buy a $2,00,000 car, well that’s an option. It is not a life or death situation. When it comes to life and death, for example cancer, I think that should not depend on your ability to pay for it. Basic care should be affordable. That’s equality, right?”

And so Dr Saadi went about finding business models that can bring down the cost of medicines. Someday he hopes to bring the same rigour to sorting out America’s education cost problem, which is depriving young children and adults from access to education.

Saadi lives with his wife Judy – a dental surgeon – whom he met while in junior college, and a daughter, Emily. He has very little he can call a family back in Bangladesh. But ever since the day he arrived in his adopted country, he has been embraced with open arms.

“When I came to Yale, I didn’t speak English that well; also I didn’t understand their English very much. We couldn’t communicate with each other. But as you can see I like to talk, and I made many friends over time; many of whom were my teachers and are my board members now. They are the most generous people,” he says.

“Don’t you think it is unusual that a kid from Kushtia goes to Harvard, Yale and establishes a multibillion biotech? It is an American story; only in America will you experience such a thing. America is designed in a way that tells people just go and give it a try. It is something I experienced with every door that opened. Every person that I needed a favour from never said no.”