Luigi Naldini, Pierluigi Paracchi, Carlo Russo. Genenta

Ital­ian gene ther­a­py play­er draws new in­vestor from Chi­na for its an­swer to CAR-T re­laps­es

So you’ve been treat­ed with one of the new-age can­cer ther­a­pies. What do you do if there’s a re­lapse and the tu­mors re­turns? 

Genen­ta Sci­ence launched four years ago out of Mi­lan in part to an­swer that ques­tion, and to­day they re­ceived $14.4 mil­lion in round three fund­ing that will pro­pel their unique gene ther­a­py through Phase I/II tri­als for mul­ti­ple myelo­ma and glioblas­toma. Backed now by mon­ey from the Chi­nese firm Qianzhan In­vest­ment Man­age­ment and Fidim, the for­mer own­er of the bio­phar­ma­ceu­ti­cal Rot­tapharm, the com­pa­ny is al­so ex­plor­ing ways of de­liv­er­ing gene ther­a­py to sol­id tu­mors that have been hard­er to reach. 

“The prob­lem Genen­ta faces is that you don’t need to be No­bel Prize brain to un­der­stand CAR-T,” CMO Car­lo Rus­so told End­points News, re­fer­ring to the pop­u­lar can­cer cell ther­a­py. “It is in­tu­itive­ly sim­ple. What we are try­ing to do is not.”

CAR-T treat­ments have been hailed in re­cent years for the break­throughs they’ve of­fered in hard-to-treat blood can­cers, but ini­tial en­thu­si­asm has been tem­pered by 1-year re­lapse rates as high as 40%.

The idea of the Genen­ta ther­a­py, called Tem­fer­on, is to pre­vent those re­laps­es by re­build­ing the pa­tient’s im­mune sys­tem with­in the tu­mor sites them­selves, called TEMS. The treat­ment in­volves in­ject­ing a lentivirus for a gene trans­fer in hematopoi­et­ic stem and prog­en­i­tor cells, trig­ger­ing in­ter­fer­on-αex­pres­sion in the tar­get­ed ar­eas. The pa­tient would then be able to fight off fu­ture re­laps­es.

This ther­a­py has ex­cit­ing po­ten­tial for long term care, Rus­so said, but not nec­es­sar­i­ly for tack­ling a fast-act­ing can­cer. He said he could en­vi­sion a fu­ture where front­line rem­e­dy such as CAR-T or chemother­a­py is used to wipe out tu­mors ear­ly and then Tem­fer­on is ad­min­is­tered for long term pre­ven­tion. 

“It’s like a vac­cine,” Rus­so says, “You’re ex­posed to an anti­gen so you will be pre­pared when you are nat­u­ral­ly ex­posed to the anti­gen.”

The mul­ti­ple myelo­ma and glioblas­toma tri­als have al­ready be­gun, Genen­ta CEO Pier­lui­gi Parac­chi told End­points, and the fund­ing will al­low them to ex­pand to 21 and 9 pa­tients in each. Parac­chi said they may al­so look in­to us­ing parts of the funds to open a clin­i­cal tri­al in the Unit­ed States.  

Genen­ta’s pre­clin­i­cal work, led by Lui­gi Nal­di­ni, ex­am­ined Tem­fer­on on an ar­ray of can­cers; mul­ti­ple myelo­ma was cho­sen for the first clin­i­cal tri­al in large part be­cause bone mar­row trans­plants are al­ready part of the dis­ease’s stan­dard of care, re­duc­ing the risk of the ex­per­i­men­tal ther­a­py. 

Like CAR-T, Tem­fer­on works by re­mov­ing bone mar­row cells, treat­ing them with a gene ther­a­py and then rein­ject­ing them in­to the pa­tient. But Genen­ta method us­es in­ter­fer­on, an old can­cer treat­ment that has been all but dis­con­tin­ued be­cause of its risks. 

“The re­ac­tion I get when I talk about in­ter­fer­on is ‘oh my god this is such an old, bor­ing drug,’” Rus­so said.

But be­cause the ther­a­py lim­its the in­ter­fer­on pro­teins to the mi­cro-en­vi­ron­ment around the tu­mor, it can be ef­fec­tive and low-risk, Rus­so said. 

Among oth­er ben­e­fits, the study on glioblas­toma will al­low re­searchers to see in the very near fu­ture if the treat­ment is hav­ing any ef­fect, as this form of brain can­cer is gen­er­al­ly fa­tal with­in 16 to 20 months.

Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Idor­si­a's brain bleed drug flunks PhI­II tri­al, a decade af­ter pre­vi­ous flop

Idorsia’s long journey with clazosentan came to an abrupt “unexpected result” Monday morning with a Phase III flop.

The Swiss biopharma said the drug did not meet the main goal of the late-stage REACT study, conducted in the US, Canada and Europe since early 2019.

The 409-patient trial tested the intravenous drug’s ability to prevent complications due to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), in which blood vessels in the brain narrow and blood accumulates around the brain’s surface, which then dials up the pressure on the brain.

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Kenji Yasukawa, Astellas CEO (Photographer: Akio Kon/Bloomberg via Getty Images)

Astel­las taps chief strat­e­gy of­fi­cer as next CEO to 'go on the ag­gres­sive'

Five years into its big R&D revamp, Astellas says it’s time for a changing of the guard.

Kenji Yasukawa, who took over as president and CEO in 2018, will step down to become chairman of the board in April, making room for Naoki Okamura to take over. Okamura joined the company in 1986 and has served in a variety of finance, business and strategy roles, including most recently as chief strategy officer.

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Clin­i­cal tri­al di­ver­si­ty da­ta show mis­match be­tween en­roll­ment and dis­ease preva­lence, GSK says

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

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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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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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.

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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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.