John Leonard, Intellia CEO

In­tel­li­a's CRISPR pro­gram that ed­its genes di­rect­ly in pa­tients shows dura­bil­i­ty in AT­TR amy­loi­do­sis

The first in vi­vo CRISPR/Cas9 gene edit­ing pro­gram has some new dura­bil­i­ty da­ta show­ing sus­tained re­duc­tion of a tox­ic pro­tein in AT­TR amy­loi­do­sis at all four dose lev­els in a small 15-pa­tient study.

In­tel­lia Ther­a­peu­tics pre­sent­ed the much-an­tic­i­pat­ed da­ta for its Re­gen­eron-col­lab­o­rat­ed NT­LA-2001 Fri­day morn­ing, adding to the ini­tial Phase I re­sults it first de­liv­ered al­most a year ago to the day.

The Cam­bridge, MA, biotech’s shares $NT­LA climbed near­ly 6% be­fore the open­ing bell Fri­day.

In­tel­lia is now in talks with the FDA and oth­er reg­u­la­tors about tri­al de­sign for a po­ten­tial piv­otal study, the Jen­nifer Doud­na-found­ed biotech said on an in­vestor call Fri­day morn­ing. The much-tracked sin­gle-dose pro­gram, which ed­its genes di­rect­ly in­side the body, is be­ing in­ves­ti­gat­ed for two dif­fer­ent man­i­fes­ta­tions of AT­TR amy­loi­do­sis — polyneu­ropa­thy, where pa­tients have pe­riph­er­al nerve dam­age, and car­diomy­opa­thy, where pa­tients’ heart mus­cles don’t work well.

All re­sults since last June have been in polyneu­ropa­thy, with Fri­day’s da­ta drop show­ing sus­tained dura­bil­i­ty in the rare con­di­tion in which tox­ic pro­tein ac­cu­mu­lates in a pa­tient’s or­gans.

Back in Feb­ru­ary, In­tel­lia had said that at the high­est dose lev­el (1.0mg/kg), six pa­tients had shown a 93% mean re­duc­tion in the tox­ic pro­tein. In the new da­ta, three of those pa­tients reached the nine-month fol­low-up point and main­tained that lev­el of TTR re­duc­tion.

The mean re­duc­tion for the three pa­tients at the sec­ond-high­est dose (0.7mg/kg) was 86%. For the longest-tracked group, dose lev­el two at 0.3mg/kg, the three pa­tients had a mean re­duc­tion of 89%.

Part II of the study, which is on­go­ing, is test­ing a dose of 80mg, the fixed-dose equiv­a­lent of the high­est dose group in Part I, the com­pa­ny said.

Headaches, in­fu­sion-re­lat­ed re­ac­tions, back pain, rash and nau­sea were the most fre­quent ad­verse events across all four dose lev­els, the biotech said. Eleven of the 15 pa­tients re­port­ed a max­i­mal ad­verse event of grade 1. The most se­ri­ous ad­verse event, which In­tel­lia said was “pos­si­bly re­lat­ed” to its treat­ment, was grade 3 vom­it­ing in a pa­tient with a med­ical his­to­ry of gas­tro­pare­sis.

“Based on the in­ter­im da­ta shared to­day, we be­lieve NT­LA-2001’s po­ten­tial to be a trans­for­ma­tion­al treat­ment for pa­tients with AT­TR amy­loi­do­sis is be­com­ing clear­er. The safe­ty, depth of serum TTR re­duc­tion and dura­bil­i­ty pro­file demon­strat­ed thus far high­lights its po­ten­tial for halt­ing and re­vers­ing the dis­ease af­ter a sin­gle dose,” said CEO and pres­i­dent John Leonard in a state­ment.

The com­pa­ny will com­plete en­roll­ment for both the polyneu­ropa­thy and car­diomy­opa­thy arms of the tri­al lat­er this year and will present the first car­diomy­opa­thy re­sults by year’s end, In­tel­lia said.

In­tel­lia is try­ing to leapfrog Al­ny­lam’s On­pat­tro and re­cent­ly ap­proved Amvut­tra, as well as Io­n­is’ Tegse­di. Those are all RNA-tar­get­ing drugs, but re­quire con­stant dos­ing com­pared to In­tel­lia’s one-time ther­a­py. On­pat­tro and Tegse­di have shown re­duced mu­tant pro­tein ex­pres­sion by about 80%.

Al­ny­lam is pur­su­ing la­bel ex­pan­sions of its On­pat­tro and Amvut­tra in AT­TR with car­diomy­opa­thy, as well.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech opens new plas­mid DNA man­u­fac­tur­ing fa­cil­i­ty in Ger­many

German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.

The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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Goldfinch Bio CEO Tony Johnson (L) and Karuna Therapeutics CEO Bill Meury

Karuna li­cens­es Goldfinch as­sets to com­pete with Boehringer In­gel­heim in neu­ro­science

Karuna Therapeutics is looking to compete with Boehringer Ingelheim on depression and anxiety with a new license to Goldfinch Bio’s assets, starting with $15 million to the shuttered biotech.

Karuna steps into an arena already being tested by Boehringer in multiple Phase II studies — the two are targeting transient receptor potential canonical 4 and 5, or TRPC4/5, which is thought to have a role in neuroscience indications. Goldfinch’s asset went through a Phase II in kidney diseases, but Karuna’s sights are set on mood and anxiety disorders for now.

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Roche's headquarters in Basel, Switzerland (Kyle LaHucik for Endpoints News)

Roche ditch­es fi­nal PhI­II for can­cer hope­ful, re­ports set­back for key drug in $1.4B buy­out

Over the past few years, Roche has released news about its AKT inhibitor ipatasertib in drips — most of them negative. The drug yielded mixed data in a key prostate cancer trial, Phase III flops in triple-negative breast cancer forced the pharma giant to pull the plug there, and in mid-2022 Roche trimmed two more early-stage indications in prostate cancer after completing the trials.

Now, the last piece of the program is gone.

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Simba Gill, Evelo Biosciences CEO

Sim­ba Gill stay­ing on at Evelo to weath­er lay­offs and a PhII fail

Simba Gill will be staying put as CEO of Evelo Biosciences for now.

Gill announced last year that he would be leaving the head position at Evelo to take on the role of executive partner at Flagship Pioneering. He was aiming to stay on until a successor was selected, but there’s a new course of action in the wake of a Phase II miss and a reduced headcount.

“I want to emphasize that I remain personally committed to Evelo and staying on to lead the organization. I continue to believe that Evelo is a remarkable opportunity in terms of the science, the platform, the type of products that we’re able to produce, and most importantly, the potential of millions of patients suffering from all stages of inflammatory disease,” Gill said on a conference call.

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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