Goran Hansson (center) announces the winners of the Nobel Prize in Chemistry, Benjamin List and David MacMillan (Claudio Bresciani/TT New Agency via AP Images)

Two decades af­ter dis­cov­er­ing a new way to con­struct mol­e­cules, David MacMil­lan and Ben­jamin List win No­bel Prize

Cat­a­lysts play a vi­tal role in drug de­vel­op­ment, dri­ving com­plex se­quences of chem­i­cal re­ac­tions to break down mol­e­cules or join them to­geth­er. But un­til just a cou­ple of decades ago, on­ly two types of cat­a­lysts were known to sci­en­tists: met­als and en­zymes.

Met­al cat­a­lysts are eas­i­ly de­stroyed by mois­ture, so while it’s sim­ple enough to de­ploy them in a lab, large-scale man­u­fac­tur­ing be­comes a chal­lenge. En­zymes, on the oth­er hand, con­sist of hun­dreds of amino acids, though fre­quent­ly enough, on­ly a few of those are ac­tu­al­ly in­volved in a chem­i­cal re­ac­tion.

In the 1990s, two re­searchers in sep­a­rate cor­ners of Cal­i­for­nia came to the same con­clu­sion: There must be a sim­pler way. Their work led to the dis­cov­ery of a third catal­y­sis that builds up­on small or­gan­ic mol­e­cules — coined asym­met­ric organocatal­y­sis — that promis­es to make mol­e­c­u­lar con­struc­tion faster, more ef­fi­cient, and “green­er.”

Now, more than 20 years lat­er, it won them a No­bel Prize.

This year’s No­bel Prize in Chem­istry went to Ben­jamin List, di­rec­tor at the Max-Planck-In­sti­tut für Kohlen­forschung, and David MacMil­lan, a Prince­ton Uni­ver­si­ty pro­fes­sor, for the de­vel­op­ment of asym­met­ric organocatal­y­sis. MacMil­lan al­most didn’t be­lieve the win at first, con­vinced it was an elab­o­rate prank pulled off by his stu­dents, ac­cord­ing to a Twit­ter post by Prince­ton. The sci­en­tists will share a prize of 10 mil­lion Swedish kro­nor, or about $1.35 mil­lion.

HN Cheng, pres­i­dent of the Amer­i­can Chem­i­cal So­ci­ety, told End­points News that the dis­cov­ery is like giv­ing chemists a “new mag­ic wand.”

HN Cheng

En­zymes are spe­cial­ists in some­thing called asym­met­ric catal­y­sis. Dur­ing chem­i­cal con­struc­tion, a sit­u­a­tion of­ten aris­es in which two mol­e­cules form, which are mir­ror im­ages of each oth­er. When mak­ing drugs, chemists of­ten want just one of those mir­ror im­ages, and en­zymes al­most al­ways form just one out of the two. How­ev­er, they tend to be slow­er, and are more ex­pen­sive to make than List and MacMil­lan’s organocat­a­lysts, Cheng said.

In Car­los Bar­bas III’s lab at the Scripps Re­search In­sti­tute in south­ern Cal­i­for­nia, List won­dered if a sin­gle amino acid — as op­posed to hun­dreds — or oth­er sim­ple mol­e­cules could do the same job as an en­zyme. He test­ed the hy­poth­e­sis with an amino acid called pro­line, which had al­ready been used as a cat­a­lyst in the ear­ly 1970s, and found the mol­e­cule to be a “dream tool.”

Mean­while, over at UC Berke­ley, List aban­doned his work on im­prov­ing asym­met­ric catal­y­sis us­ing met­als, and was work­ing on de­sign­ing sim­ple or­gan­ic mol­e­cules to do the trick in­stead. He se­lect­ed sev­er­al or­gan­ic mol­e­cules with the right prop­er­ties, then test­ed their abil­i­ty to dri­ve a Diels-Alder re­ac­tion, which chemists use to build rings of car­bon atoms. The rest is his­to­ry.

MacMil­lan pub­lished his work just be­fore List in 2000, coin­ing the term organocatal­y­sis. It’s a process that’s proven not on­ly to be faster – speed­ing up the syn­the­sis of one com­pli­cat­ed tox­in called strych­nine by 7,000 times — but al­so sus­tain­able, Cheng not­ed.

“Organocat­a­lysts tend to be small­er mol­e­cules, and they are rel­a­tive­ly less tox­ic, and they can be run un­der mild con­di­tions in most cas­es,” he said. “So these re­ac­tions are green­er.”

A raft of promi­nent sci­en­tists took to Twit­ter to con­grat­u­late List and MacMil­lan, in­clud­ing top ge­neti­cist and White House sci­en­tif­ic ad­vi­sor Er­ic Lan­der: “It’s an out­stand­ing ex­am­ple of how ba­sic re­search can lead to new tools that dri­ve the green rev­o­lu­tion, cre­ate more ef­fi­cient in­dus­tries, and make drugs more ef­fi­cient­ly,” he wrote.

Oth­ers in the in­dus­try, though, ex­pressed dis­ap­point­ment that mR­NA pi­o­neer Katal­in Kariko — the Hun­gar­i­an bio­chemist whose re­search con­tributed to the swift de­vel­op­ment of Covid-19 vac­cines — didn’t take home a No­bel Prize. On­ly sev­en women in his­to­ry have won the No­bel Prize in Chem­istry, out of 188 to­tal re­cip­i­ents.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data is messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data is exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.

Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

Just as Avoro Capital’s campaign to derail Merck’s proposed $11.5 billion buyout of Acceleron gains steam, Bristol Myers Squibb is leaning in with some hefty counterweight.

The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.

Boost­er bo­nan­za: FDA en­dors­es 'mix-and-match' scheme, and Mod­er­na and J&J too

The FDA late Wednesday signed off on authorizing the use of heterologous — or what FDA calls a “mix and match” of a primary vaccine series and different booster doses — for all currently available Covid-19 vaccines, in addition to separately authorizing Moderna and J&J boosters.

On the mix-and-match approach, which FDA officials insisted isn’t too confusing in a press conference, the agency offered the example of an 18-year-old who received the J&J shot at least two months ago and may now receive a single booster of the J&J, a half dose of the Moderna, or the Pfizer-BioNTech booster.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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