As tar­get­ed ther­a­pies get ever more pre­cise, Deer­field un­veils $50M bet on a Har­vard pro­fes­sor's chem­istry in­sights

Be­hind the seem­ing­ly sim­ple con­cept of tar­get­ed can­cer ther­a­pies is the drug de­vel­op­er’s headache that the tar­get is al­ways chang­ing. Each gen­er­a­tion of ki­nase in­hibitors may be os­ten­si­bly hit­ting the same onco­gene, but in ad­di­tion to block­ing the wild­type onco­gene, they must now al­so ad­dress the mu­ta­tions that have de­vel­oped along the way, spurring re­sis­tance to cur­rent drugs.

The more those tar­get ki­nas­es evolve, too, the more they could re­sem­ble off-tar­get ki­nas­es you don’t want to bind. So each it­er­a­tion re­quires more se­lec­tiv­i­ty — some­times down to dif­fer­ences of a few atoms.

Matthew Shair

Matthew Shair be­lieves chem­istry can evolve fast enough to pro­vide an an­swer.

By uti­liz­ing struc­ture-based drug de­sign — by now a fa­mil­iar tool in small mol­e­cule de­vel­op­ment — his biotech start­up, Nu­va­lent, has spent the past cou­ple of years on two com­pounds that tar­get the tu­mor dri­vers ROS1 and ALK for the clin­ic.

Now that the $50 mil­lion in Se­ries A cash has pro­pelled them to the cusp of the clin­ic, with the first hu­man stud­ies planned for the sec­ond half of 2021, the Har­vard pro­fes­sor is ready to tease the biotech world with a glimpse of his ef­forts.

“I see Nu­va­lent emerg­ing as one of the (if not the) pre­mier com­pa­nies de­vel­op­ing tar­get­ed can­cer ther­a­peu­tics,” Cameron Wheel­er, a part­ner at Deer­field who helped start the com­pa­ny and now chairs its board, wrote in an email.

Nu­va­lent’s ap­proach, Shair told End­points News, starts with go­ing to physi­cians and seek­ing their in­put on what prop­er­ties they want in a drug.

“What hasn’t been pos­si­ble for in­stance in the ROS1 space is to have a mol­e­cule that works against the known mu­tants — the known mu­ta­tions, in­clud­ing ones that are just re­cent­ly seen in pa­tients and even the ROS1 pro­tein be­fore it’s mu­tat­ed, so-called wild­type pro­tein,” he said, “and avoid­ing in­ter­act­ing with an off tar­get called TRK.”

Cameron Wheel­er

The next step re­quires a lot of crys­tal struc­tures and rel­e­vant in­for­ma­tion to un­der­stand the mu­ta­tions as well as the in­ter­ac­tion be­tween small mol­e­cule and lig­and, in or­der to lo­cate po­ten­tial drug can­di­dates that sit in the mid­dle of that con­vo­lut­ed Venn di­a­gram.

CEO James Porter has been lead­ing a team of 14 sci­en­tists to re­fine the twin lead pro­grams, en­sur­ing they are pre­cise­ly tai­lored to the prob­lem, while ap­ply­ing any in­sights to a pipeline of oth­er tar­get­ed drugs.

While mul­ti­ple drugs have been ap­proved for ROS1-pos­i­tive non-small cell lung can­cer, pa­tients who have pro­gressed cur­rent­ly have no op­tion be­yond first-gen­er­a­tion drugs. Sim­i­lar­ly, an emerg­ing ALK+ pa­tient pop­u­la­tion presents a “wide open space” for Nu­va­lent’s im­me­di­ate fo­cus.

“We rec­og­nize that if we are rig­or­ous with project se­lec­tion, ex­e­cu­tion of our pro­grams, we have dis­ci­plined de­ci­sion-mak­ing, we can use our skills in chem­istry to cre­ate some so­lu­tions for pa­tients,” he said, adding that Shair has been close­ly in­volved with each of the steps as the head sci­en­tif­ic ad­vi­sor.

James Porter

The two have known each oth­er since Porter be­came one of the first chemists at In­fin­i­ty Phar­ma­ceu­ti­cals, where Shair was a co-founder.

“Twen­ty years ago, every com­pa­ny like Ari­ad and Mil­len­ni­um and Enan­ta, they had their own mouse fa­cil­i­ty on site,” Shair re­flect­ed. “Be­cause you couldn’t out­source phar­ma­co­ki­net­ic stud­ies, you couldn’t out­source in vi­vo ef­fi­ca­cy. Now it’s all out­source­able. And every­thing — just about every­thing is out­source­able ex­cept for I think the de­sign of the mol­e­cules, the de­sign of your clin­i­cal tri­als, the de­sign of your pro­grams. So that’s a huge sea change which has — I like to think about it, it’s de­moc­ra­tized drug dis­cov­ery. It al­lows a team of 10, 20, 30 peo­ple, to put 2 com­pounds in the clin­ic. You could nev­er do that 20 years ago.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Af­ter sell­ing to Genen­tech, the old Je­cure team is back at an RNA-fo­cused start­up — and more en­thu­si­as­tic than ever

When Genentech swooped in to buy NASH-focused Jecure Therapeutics back in 2018, a handful of the startup’s executives weren’t quite ready to disperse.

It had been just three years since Jecure launched with a preclinical portfolio of NLRP3 inhibitors — and the takeover came sooner than anyone, including CEO Jeff Stafford, had expected. So he got talking with James Veal and Gretchen Bain, two serial entrepreneurs in charge of Jecure’s R&D.

Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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