He was creating the building blocks for drug developers worldwide. Then Russia started to bomb Kyiv

It was just last month, with the Covid-19 situation having calmed down in Kyiv, that Ivan Kondratov had been able to return to his office a couple days per week. He managed a slew of medicinal chemistry projects, including the building of “target libraries” for clients, mostly large biopharma companies around the world.

His employer, Enamine, had become a pillar of global drug development, its Rolodex of clients steadily growing along with its catalog of chemical compounds for drugmakers to test in creating potential treatments.

But on Feb. 24, all of that came to a halt as Kondratov and hundreds of thousands of other Ukrainians were stunned awake by the sound of explosions. And everything changed for the chemists and scientists.

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“The situation developed really, really quickly,” Kondratov told STAT, speaking by phone from a town in northwest Ukraine where he had sought refuge. “On Thursday morning they started to bomb and attack, and many families, many of our co-workers just took their families and got out, went away.” Suddenly, reading the latest published research, figuring out what chemical building blocks his team could synthesize, mattered little. “This was my routine. And now I don’t even think about that,” he said.

Enamine, headquartered in a former Soviet chemical plant on the left bank of the Dnieper River that splits Kyiv, is one of the major providers of chemicals used in pharmaceutical labs from Boston to Tokyo. It has been instrumental in the Covid Moonshot effort to create a pill against the disease.

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It is one of several companies that have pioneered a new industry over the past three decades, longtime drug discovery researcher Derek Lowe said. The Ukrainian chemical world grew out of the fall of the USSR by capitalizing on a reserve of “weird” compounds that hadn’t been explored in countries such as the U.S. because of the divide between Soviet chemistry research and the Western world.

Enamine, as well as two other Ukrainian companies, Otava Chemicals and Life Chemicals, filled a gap in the market, offering “interesting,” ready-to-use building blocks that drug developers could easily patch into their work, and creating custom libraries of these chemical tidbits for companies. “It’s really changed the way medicinal chemists work,” said Lowe, who works at Novartis (but was not speaking on behalf of the company).

Instead of having to do that work in-house, companies could outsource the work to Ukraine, making it more efficient and affordable. This business has since become a crucial part of drug development around the world. “I’m pretty sure that most of drug discovery projects which led to development of drug candidates and drugs during the last five years, more or less, have dealt with our products and services,” Kondratov said. Perhaps the most impressive of the company’s offerings is a catalog of 20 billion synthetic compounds that companies can peruse digitally and order à la carte.

The invasion threatens to derail that and other early-stage research, since so many companies rely on Ukrainian chemistry. “Now, suddenly, there’s a bunch of reagents that we can’t get anymore,” Lowe said. Across the industry, chemists are having to make up for the supply issue, whether that means developing small molecules in-house or finding another company to provide them.

The average person doesn’t feel that squeeze, but in the long term, “it would put a dent in the drug pipeline for sure,” said Lowe. Warehouses full of chemical building blocks could be destroyed, libraries of them never released. “All that just gets blown out by an event like this. And it unfortunately shows you the fragility of something like science and research and intellectual pursuits,” he said. “Because none of these stand up very well to cluster bombs.”

Enamine’s Kyiv operations stopped on Feb. 24. Its 1,000-person staff is scattered, each employee faced with the decision of whether to flee or stay, knowing the threat could continue indefinitely.

That Thursday morning, after the explosions woke him up around 6 a.m., Kondratov tried to cut through the mess of rumors and misinformation online, and arrived at this: He had to leave Kyiv. “I did understand that it’s really necessary to transfer my family, to take my family as far as possible,” he said.

Together with a few other families, Kondratov instructed his children, 10 and 6 years old, to pack up their clothes, and with a few other families, they loaded their vehicles and embarked on the long trek to the west. Along the way, they encountered traffic jams and “huge, huge, huge queues” at gas stations that were limiting each car to 30 liters, then 20.

He was lucky. He got out of central Ukraine before the reportedly indiscriminate attacks by Russian troops on residential areas. “Now I see how classmates of my kids, many of them spent their time in the shelters, sometimes the whole night,” he said. His parents caught one of the last flights out of the country on the day before the invasion began, and went to Paris to stay with Kondratov’s sister.

But Kondratov didn’t feel lucky after 12 hours of driving, when he dropped off his wife and children in Poland and drove to Volodymyr, a town in northwest Ukraine, to stay indefinitely. Because of his age, he is unable to leave Ukraine in case he’s needed to defend the country. Many of his friends did the same — tried to save their families first, and then found places to stay in villages, towns, and cities in western Ukraine. They volunteer to help in any way they can. For Kondratov, that meant helping local police patrol the streets.

Some men he knows have gone back to Kyiv to join the fight. Other friends could not leave at all. In cities like Chernihiv — not far from Kyiv, in the northern part of the country near Belarus — which was quickly surrounded by Russian troops, it’s impossible to get out.

“I just got the messages from them that they’re sitting in the shelters, sitting underground, listening for the bombs, and it’s terrible,” Kondratov said. STAT spoke with him before reports on Friday of explosions in Lutsk, about 50 miles east of Volodymyr.

War is not foreign to most Ukrainians. The conflict with Russia in the eastern part of the country has simmered in the background of life for years, said Kondratov, who was raised by chemist parents about 10 kilometers from that fighting zone. He had watched that conflict escalate and, in the past few years, cool down. And he knew, back in December, that Russian troops assembling at the border with Ukraine meant there was a high risk of an invasion.

But the feeling of war, the lived reality of what it does to one’s mind, one’s priorities, to be under attack — that is surreal.

“It’s difficult to explain,” Kondratov said. “I see so many things that I should do or I can do, and I understand that I absolutely have no time or resources to do all of them. There are things which I should do to save our people. There are some actions which I should do to save at least a part of our clients because, obviously, we understand that as long as this war would continue, we start to lose our clients. … There are many tough decisions which we should make at this time.”

Back in Kyiv, those who stayed helped clear out flammable materials from labs on Enamine’s campus, just in case the buildings are bombed. The company announced plans to relocate some of its 700 chemists to Riga, Latvia, where Enamine stores compounds for customers in Europe. The now-shuttered Kyiv campus was home to the bulk of the company’s work, but an Enamine facility in New Jersey has allowed some business to continue.

From the left to right: Veronika Shoba, Basudeb Mondal, Uttam Dhawa, Arghya Deb, Praveen Tiwari, Santosh Chaudhary, Amedeo Vetere and Prashant Singh. Researchers at the Broad Institute of Harvard and MIT hold a Ukrainian flag in the lab on Friday, March 11, two weeks after Russian troops began their invasion. Scientist Veronika Shoba (far left) grew up in Lviv, Ukraine, and is concerned about how the invasion threatens to derail the country’s important work in chemistry. Courtesy Veronika Shoba

That’s how Veronika Shoba received a package from Enamine on Feb. 25, one day after the invasion. Shoba, a scientist at the Broad Institute of MIT and Harvard, was surprised when she received a 500-milligram shipment of N-benzyl-N-methylaminosulfonamide, a chemical building block Shoba’s lab is using to make a novel potential anti-cancer therapy.

A Belarus native who was raised in the western Ukrainian city of Lviv, Shoba is all too familiar with the situation her country is facing. Every morning, before work, she spends several hours reading the news, messaging friends and family in Ukraine to check on their wellbeing, and looking on social media for people she can help connect with resources, despite being thousands of miles away.

“I keep thinking, ‘Who else could be there? Who else could I help?’” Shoba told STAT. “Even with people who I had huge fights with before and I thought I would never talk to that person, we are friends, back again, because it doesn’t matter.”

Then, she goes to work at the Broad, where she updates her colleagues on the situation. In her free time, Shoba investigates connections between Russian oligarchs and institutions such as Harvard, and she writes letters appealing to senators and other power players, hoping someone might have the leverage needed to help Ukraine defend its airspace. Life is hectic, consumed by the invasion. “I don’t think I’m getting much work done,” she said, noting the Broad has been supportive.

Shoba, like many Ukrainians living abroad, is overwhelmed by the shocking toll — the breadth and depth of damage that is being done. Death and property destruction are accompanied by a universe of a million smaller losses. As a kid interested in science, Shoba competed in international science Olympiads in the spring, preparing for months ahead of time. She tears up when she thinks of the talented children who have been working so hard for this year’s competition, who won’t get to have that experience. The university where they used to prepare was bombed, destroyed.

“I’m shocked. But it also made me think a lot about previous wars, which were not in my home country, but which I did not pay attention to,” she said. “Since it was not about me, not about my family and my friends, I would read about it in the news, I would just feel sad but I don’t think I fully understood the tragedy behind war … it’s very abstract until you are part of it.”

Source: STAT