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.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Matt Gline (L) and Vivek Ramaswamy

Scoop: Vivek Ra­maswamy is hand­ing the CEO job to a top lieu­tenant at Roivant — but he’s not ex­act­ly leav­ing the biotech scene

Over the past 7 years since founding Roivant, Vivek Ramaswamy has been a constant blur of biotech building motion.

He launched his first biotech with an Alzheimer’s drug he picked up cheap, and watched the experiment implode in one of the highest profile pivotal disasters seen in the last decade. But it didn’t slow the 30-something exec down; if anything, he hit the accelerator. Ramaswamy blazed global paths and went on to raise billions to spur the creation of a large lineup of little Vants promising big things at a fast pace. He sold off a section of the Vant brigade to Sumitomo Dainippon for $3 billion. And more recently the relentless dealmaker has been building a computational discovery arm to add an AI-driven approach to kicking up new programs and companies, supplementing the in-licensing drive while pursuing advances that have created more than 700 jobs at Roivant, with $2 billion in reserves.

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José Baselga, AstraZeneca cancer chief (Brent N. Clarke/FilmMagic via Getty Images)

As­traZeneca's Calquence nabs an­oth­er win against Im­bru­vi­ca, but Eli Lil­ly is on its heels

Three years after first launching Calquence as a second generation BTK inhibitor, AstraZeneca continues to tout new data to compete with J&J and AbbVie’s first generation blockbuster Imbruvica.

The British pharma announced on Monday that Calquence passed a head-to-head Phase III study against Imbruvica in chronic lymphocytic leukemia, proving non-inferior — i.e. just as good — as the older drug. Although AstraZeneca did not break down any of the numbers, they said the drug proved superior on safety, triggering fewer cases of atrial fibrillation, an irregular heartbeat that can lead to stroke or heart failure.

Can strug­gling Iterum turn the cor­ner to an an­tibi­ot­ic suc­cess sto­ry? They will know in six months

More than five years after Corey Fishman and Michael Dunne dusted sulopenem off Pfizer’s shelves — the second castoff antibiotic they’ve brought out of the pharma giant — and founded Iterum Therapeutics around that single drug, they have lined up a quick shot at approval with priority review from the FDA.

The decision, six months from now, will mark a make-or-break moment for a struggling biotech that has just enough cash to keep the lights on until the third quarter.

Bahija Jallal, Immunocore

Buried in Im­muno­core's IPO fil­ings? A kick­back scheme from a now for­mer em­ploy­ee

Immunocore spent much of 2019 dealing with the fallout of the Neil Woodford scandal, as the former star investor’s fall crashed the biotech’s valuation out of unicorn range. Now it turns out that the company spent 2020 dealing with another internal scandal.

The longtime UK biotech darling disclosed in their IPO filing last week that they had fallen victim to an alleged kickback scheme involving one of their employees. After a whistleblower came forward, they said in their F-1, they spent the summer and spring investigating, finding fraud on the part of an employee and two outside vendors.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Covid-19 roundup: Mod­er­na dou­bles down on Covid-19 with new boost­er tri­als; Aus­tralia plans do­mes­tic pro­duc­tion of As­traZeneca vac­cine amid dis­tri­b­u­tion lag

As Merck bows out of the global race to develop vaccines for Covid-19, Moderna is doubling down to make sure they can quell new variants that have recently emerged and quickly spread.

The Cambridge, MA-based biotech put out word on Monday that in vivo studies indicate their mRNA vaccine works well enough against two strains first detected in the UK and South Africa. But with a six-fold reduction in neutralizing titers observed against the latter strain, the company is launching a new study of a booster version to make sure it can do the job.

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Jean-Christophe-Hyvert, Lonza

Lon­za look­ing to build on 'd­if­fer­en­ti­at­ed ad­van­tage' in Covid-19, CD­MO mar­ket­place in 2021

It’s not new for Lonza, the Swiss CDMO nearing its quasquicentennial anniversary, to be in the upper echelon of the biotech manufacturing industry.

But 2020 — as it was for many CDMOs — was a special year even by Lonza’s standards. The company inked a deal to produce 1 billion worldwide doses of Moderna’s Covid-19 vaccine and tapped pharma vet Pierre-Alain Ruffieux to lead its operations, moves which have allowed Lonza to make a myriad of other deals that will continue to ramp up its global production capacity.

News brief­ing: Jef­frey Lei­den to chair Tmu­ni­ty board of di­rec­tors; Op­di­vo wins new ap­proval in ad­vanced RCC

Longtime Vertex CEO Jeffrey Leiden is taking on a new role.

Leiden has been appointed chairman of Tmunity’s board of directors, the company announced Monday. The move comes about a year and a half after Leiden announced he’d be stepping down from his position at Vertex.

Vertex saw immense growth under Leiden, leading the company from its exit out of hepatitis C, when cures were moving in, and into cystic fibrosis. The company’s cystic fibrosis triple combo therapy Trikafta is already its best-seller, reaching the distinction just six weeks after launch and recording the strongest first quarter of sales for any drug, per some estimates.