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.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,600+ biopharma pros reading Endpoints daily — and it's free.

Joan Butterton, Merck Research Laboratories VP of global clinical development, infectious diseases (Merck)

Mer­ck­'s ex­per­i­men­tal HIV drug is­la­travir hits with a PhI­II com­bo win and FDA fil­ing plans

Back in March, Merck and Gilead agreed to a partnership to challenge GlaxoSmithKline on long-acting HIV meds — by combining one drug from both Merck and Gilead that had shown potential. While Gilead brought its capsid inhibitor lenacapavir, Merck brought islatravir into the deal — a small molecule that the pharma acquired in 2012 from a small Japanese firm.

While that partnership is ongoing, islatravir is coming out of 2 Phase III pivotal trials with back-to-back successes and plans to beat a quick advance to the FDA.

Gil Beyen, Erytech CEO

A transat­lantic biotech flags a painful PhI­II can­cer flop, wav­ing a white flag

More than 4 years after little Erytech inflated some rare passion for its stock with upbeat Phase IIb data for their lead drug in pancreatic cancer, they’ve let the air out of the party balloons.

The transatlantic biotech $ERYP put the word out Monday morning that its drug eryaspase flopped in a Phase III pivotal for second line metastatic pancreatic cancer, slamming its stock, which plunged more than 30%.

Preston Klassen, Metacrine CEO

An­oth­er NASH play­er re­treats from bat­tered field af­ter tox­i­col­o­gy study flags po­ten­tial de­lay

NASH, the notorious liver disease afflicting an increasing number of Americans, has always been the focus at Metacrine ever since serial entrepreneur Rich Heyman unveiled the first round of financing all the way back in 2015.

Not anymore.

The San Diego-based biotech is halting its NASH program and choosing instead to prioritize its effort in pushing the same FXR agonist, MET642, into a Phase II trial for inflammatory bowel disease.