Imara at­tempts to spin weak da­ta in­to an 'en­cour­ag­ing' re­sult — but in­vestors aren't hav­ing it

Imara un­veiled da­ta from two sub­groups of a Phase IIa tri­al for its lead com­pound Wednes­day, aim­ing to con­jure up a pos­i­tive light de­spite chal­lenges tied to the Covid-19 pan­dem­ic. But in­vestors weren’t buy­ing it and sent the com­pa­ny’s shares in­to a tail­spin.

The ex­per­i­men­tal drug, dubbed IMR-687, is be­ing eval­u­at­ed for sick­le cell dis­ease as both a monother­a­py and in com­bi­na­tion with hy­drox­yurea. In the monother­a­py sub­group, Imara re­port­ed IMR-687 showed no mean­ing­ful changes in F-cells, fe­tal he­mo­glo­bin (HbF) lev­els or Hb lev­els from base­line af­ter 24 weeks.

Ad­di­tion­al­ly, in the com­bo sub­group, the can­di­date demon­strat­ed nu­mer­i­cal in­creas­es in F-cells and HbF lev­els from base­line, but Hb lev­els did not mean­ing­ful­ly change. But Imara was un­able to mea­sure the dif­fer­ence against a place­bo in both groups, as pa­tients in those arms could not be eval­u­at­ed due “in part” to missed study vis­its, the com­pa­ny said.

Ul­ti­mate­ly, on­ly one place­bo pa­tient in the com­bi­na­tion group had ap­pro­pri­ate bio­mark­er da­ta af­ter the 24-week pe­ri­od, and p-val­ues were not re­port­ed. Imara at­tempt­ed to spin those less-than-stel­lar re­sults in­to a win in a re­lease, but in­vestors saw through the ef­fort im­me­di­ate­ly.

“I am en­cour­aged by the in­cre­men­tal da­ta from this read­out, es­pe­cial­ly in light of the COVID-19 pan­dem­ic chal­lenges,” lead in­ves­ti­ga­tor Biree An­de­mari­am said in a state­ment. “This in­cludes a fa­vor­able safe­ty pro­file of IMR-687, low­er rate of VOCs/SCPCs and VOC-re­lat­ed hos­pi­tal­iza­tions in the Pop­u­la­tion A1 monother­a­py arm and im­prove­ments in sev­er­al bio­mark­er re­sults across both the monother­a­py and com­bi­na­tion groups.”

Imara $IM­RA shares were down 33% in ear­ly trad­ing Wednes­day.

The re­sults make up part of a 93-pa­tient Phase IIa tri­al, study­ing four dif­fer­ent dose lev­els across the monother­a­py and com­bi­na­tion reg­i­mens. Wednes­day’s monother­a­py da­ta come from a reg­i­men of a once-dai­ly dose of 100 mg through 4 weeks, which es­ca­lates to 200 mg through an ad­di­tion­al 20 weeks.

In the com­bi­na­tion group, pa­tients took a 50 mg dose once a day on top of stan­dard of care HU, with es­ca­la­tion af­ter 4 weeks to 100 mg for the re­main­ing 20 weeks. There were 18 to­tal in­di­vid­u­als in this monother­a­py co­hort and 14 in the com­bo por­tion.

Imara can still hang its hat on in­ter­im da­ta from the oth­er sub­groups in the study, which showed the high­er dose of the monother­a­py had sta­tis­ti­cal­ly sig­nif­i­cant in­creas­es in F-cells, as well as a dose-de­pen­dent in­crease in HbF lev­els in adults. There was al­so a mean in­crease from base­line of 1.7% in HbF per­cent­age in the 100 mg / 200 mg dose group through week 24, a fig­ure that SVB Leerink an­a­lyst Joseph Schwartz had deemed promis­ing.

Ahead of Wednes­day’s da­ta, Schwartz had been hop­ing to see a fur­ther rise in this spe­cif­ic da­ta point, re­gard­less of whether or not it reached the 3% lev­el the FDA set as the thresh­old for the Phase IIb study that launched in Au­gust. But the over­all per­cent change in monother­a­py re­port­ed Wednes­day was -1.1%, even though Imara not­ed an ab­solute, dose-de­pen­dent in­crease in HbF of 1.3% when pa­tients es­ca­lat­ed from 100 mg to 200 mg.

Schwartz wrote Wednes­day that he does not be­lieve the da­ta is a good in­di­ca­tor of the up­com­ing Phase IIb re­sults, and still be­lieves the 3% fig­ure is achiev­able. He al­so not­ed that the dos­es be­ing used in that study are much high­er — up to 400 mg — than those in Phase IIa, with signs point­ing to longer and high­er dos­es re­sult­ing in bet­ter ef­fi­ca­cy.

IMR-687 was one of a group of small mol­e­cule PDE9 in­hibitors that Imara had li­censed from Lund­beck. The the­o­ry is that block­ing PDE9 in­creas­es cyclic GMP lev­els, which is as­so­ci­at­ed with re­ac­ti­va­tion of fe­tal he­mo­glo­bin and thus re­store some func­tion­al­i­ty im­paired in blood dis­or­ders. Imara went pub­lic in March fol­low­ing a $75.2 mil­lion IPO raise.

This ar­ti­cle has been up­dat­ed to in­clude SVB Leerink’s Joseph Schwartz’s most re­cent analy­sis, pub­lished late Wednes­day morn­ing.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

David Baker working with a student on their protein design (Jason Mast)

Sci­en­tists are fi­nal­ly learn­ing how to de­sign pro­teins from scratch. Drug de­vel­op­ment may nev­er be the same

SEATTLE — It’s a cloudy Thursday afternoon in mid-July and David Baker is reclining into the futon in his corner office at the University of Washington, arms splayed out like a daytime talk show host as he coaches another one of his postdocs through the slings and arrows of scientific celebrity.

“Be jealous of your time,” he says, before plotting ways of sneaking her out of Zooms. “It’s this horrible cost to science that you’re tied up in some stupid meeting.”

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

Amidst R&D reshuf­fle, Ver­tex ex­pands its pres­ence in Boston, aim­ing to be­come num­ber one

Vertex Pharmaceuticals has been one of the buzzier names in the bustling Boston biotech scene, but now the company is looking to vault to number one status — at least in terms of physical footprint.

At a ribbon cutting on Tuesday for its new Jeffrey Leiden Center for Cell and Genetic Therapies at the Boston Seaport, Vertex announced it would embark on a new project: The company will build a 344,000 square foot facility in the seaport to accommodate the company’s growing R&D needs, especially in its cell and gene therapies program.

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Patty Murray, D-WA (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Warren Buffett, Berkshire Hathaway CEO

Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.

Clay Siegall (Photo by Dimitrios Kambouris/Getty Images for Gabrielle's Angel Foundation)

UP­DAT­ED: Clay Sie­gall re­signs from Seagen amid in­ves­ti­ga­tion in­to do­mes­tic vi­o­lence claims

A week after Seagen revealed that longtime CEO Clay Siegall was on leave due to an allegation of domestic violence, he has resigned.

Since that shocking revelation, more details about the claims have emerged into the public eye. As Endpoints News reported, Siegall was arrested on April 23. A police report about that night and a subsequent temporary restraining order described a pattern of abusive behavior against his wife and a physical altercation that left her with multiple bruises. Siegall denied the claims.

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FDA lob­bies Con­gress over rare dis­ease court rul­ing with wide im­pli­ca­tions

Usually reserved for making decisions on drug applications or enforcing what Congress stipulates, the FDA is now dipping its toe into the wild world of congressional politics as it attempts to fix a major court decision that could have a chilling effect on rare disease R&D.

The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.