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.”

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Michael Rome (Foresite)

In search of 'house­hold health­care brands of the fu­ture,' Fore­site Cap­i­tal rais­es $969M to sa­ti­ate a tech-heavy ap­petite

Back in April 2018, just before Foresite Capital unveiled its $668 million Fund IV and a strategy to focus on tech-driven life science bets, one of its portfolio companies quietly made an announcement.

Fount Therapeutics, a drug discovery outfit backed by Foresite and Eshelman Ventures, had raised $22 million in Series A cash to hatch several fledgling spinouts. “The first ‘NewCo,’ Kinnate, will be focused on developing precision oncology treatments,” read a press release.

CEO Fabrice Chouraqui (Cellarity)

Flag­ship up­start Cel­lar­i­ty gath­ers $123M to fi­nance its ex­plo­ration of cell be­hav­ior, blaz­ing a new path to build­ing a broad pipeline

Right from the start, the discovery plan at Flagship-spawned Cellarity was to take their cues from cell biology and follow them to new drugs. Rather than start with a target and develop a drug to hit it, they’d use new technology to digitally map cell behavior and then develop new drugs from what they learned.

“Over the past decades it has always been about finding a target, about reducing a disease to a single molecular target,” says Fabrice Chouraqui, the Novartis vet who was recruited to run the operation about 9 months ago. “And that approach has produced thousands of life-saving medicines. Yet, this approach has limitations. A molecular target approach is fine when you talk about a simple disease, but for very complex diseases like neurodegeneration, like metabolic disease, like cancer, you hope to really harness the complexity of human biology.

Masayoshi Son, SoftBank CEO (glen photo/Shutterstock)

Japan's Soft­Bank plots bil­lions in biotech in­vest­ments in move that could keep the val­u­a­tion flood ris­ing — re­port

The valuation crazy train in biotech continues to roll into the new year with more than a dozen companies taking a chance on Nasdaq and money flowing in from all sides. Now, a Japanese institutional investor is reportedly weighing an entry into the market in a big way — will it keep the bitcoin-esque flood rising?

Already a part-time investor in biotech, SoftBank could drop billions of dollars into the industry as part of helmsman Masayoshi Son’s plan to spend around $80 billion of the firm’s own assets, according to a report from Bloomberg citing people familiar with the plan.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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