Rob Etherington, Clene Nanomedicine CEO

Clene claims its PhII MS tri­al, half its in­tend­ed size, cleared the pri­ma­ry goal. But can the biotech af­ford PhI­II?

Clene Nanomed­i­cine said its gold nanocrys­tal-based drug can­di­date, which failed an ALS tri­al last year, was bet­ter than place­bo in a mid-stage study of pa­tients with mul­ti­ple scle­ro­sis. But there are some big caveats to flag here.

The Phase II VI­SION­ARY-MS study en­rolled less than half (73 of 150) of the planned pa­tient pop­u­la­tion, which the biotech has pre­vi­ous­ly at­trib­uted to Covid-19. The tri­al was con­duct­ed in Aus­tralia, a point men­tioned dur­ing an in­vestor call when not­ing the study was main­ly white (95% of pa­tients). And it failed in the in­tent-to-treat group, on­ly pass­ing muster on the pri­ma­ry end­point af­ter ex­clud­ing a group of pa­tients.

The Salt Lake City biotech end­ed up con­duct­ing the pri­ma­ry analy­sis in a mod­i­fied in­tent-to-treat pop­u­la­tion (mITT), which en­tailed ex­clud­ing da­ta from a 9-pa­tient site with “LCLA test­ing ex­e­cu­tion er­rors” and ex­clud­ing 25-foot walk da­ta from an­oth­er pa­tient with a “change in mo­bil­i­ty as­sist de­vice.”

LCLA, or low-con­trast let­ter acu­ity, was the pri­ma­ry end­point of the study, which was met when view­ing the mITT pop­u­la­tion but not achieved when an­a­lyz­ing the ITT, the biotech said Mon­day morn­ing. Re­sults for the ITT group were “di­rec­tion­al­ly con­sis­tent with the mITT re­sults” but didn’t clear the sta­tis­ti­cal­ly sig­nif­i­cant hur­dle.

Robert Glanz­man

With the pri­ma­ry out­come re­sults, the com­pa­ny is al­ready plan­ning a late-stage tri­al, CMO Robert Glanz­man said on the in­vestor call. Dose da­ta haven’t been ful­ly an­a­lyzed yet, he not­ed.

Shares $CLNN slid more than 8% be­fore the open­ing bell Mon­day. And the stock had fall­en 54% over the past year, when it closed on Fri­day.

For the com­pa­ny to get in­to a Phase III, the biotech will like­ly need to raise more cap­i­tal. In the in­vestor pre­sen­ta­tion, Clene said it had “suf­fi­cient cash to hit key mile­stones in 2022.” The com­pa­ny had $26.3 mil­lion as of June 30, which is enough to car­ry it in­to next year. De­spite a bear mar­ket, mul­ti­ple biotechs have gone to the mar­ket with­in min­utes or hours of drop­ping pos­i­tive clin­i­cal da­ta, hop­ing tri­al wins equate to fast cash.

The study test­ed CNM-Au8 in pa­tients with sta­ble re­laps­ing re­mit­ting mul­ti­ple scle­ro­sis over a 48-week pe­ri­od at 11 tri­al sites. Pa­tients re­ceived 15 mg, 30 mg or place­bo dai­ly as an ad­junc­tive ther­a­py to dis­ease mod­i­fy­ing ther­a­pies cur­rent­ly avail­able.

On the main goal of LCLA let­ter change in the clin­i­cal­ly af­fect­ed eye, the p-val­ue was 0.056. The pre-spec­i­fied sta­tis­ti­cal thresh­old was set at a p-val­ue of 0.10.

The drug al­so met the sec­ondary end­point of the mod­i­fied Mul­ti­ple Scle­ro­sis Func­tion­al Com­pos­ite (mMS­FC) — which ob­served vi­sion, walk­ing, cog­ni­tion and oth­er mea­sures — with a p-val­ue of 0.0138. CNM-Au8 did not pass the sec­ondary end­point of time to re­peat­ed clin­i­cal im­prove­ment.

Asked about dos­ing on the in­vestor call, Glanz­man said dos­ing needs to be “ex­plored in fu­ture stud­ies more ful­ly” but that “it’s very pos­si­ble that even a low­er dose could be ef­fec­tive over the long term.”

“It’s im­por­tant to re­mem­ber that MS is a chron­ic dis­ease and we will ful­ly ex­pect that a pa­tient will be tak­ing CNM-Au8 for a life­time and it will take more study to un­der­stand the time course,” Glanz­man said.

Clene ob­served no treat­ment-re­lat­ed se­ri­ous ad­verse events. Treat­ment emer­gent ad­verse events were “pre­dom­i­nant­ly mild-to-mod­er­ate and tran­sient,” the biotech said. One sub­ject on the study drug and one on place­bo dropped out of the study due to TEAEs.

The mean age of pa­tients was 38.7 years. The mean time from di­ag­no­sis was 5.5 years and 49 months since re­lapse. Of the 73 pa­tients, 51 were women.

In the po­ten­tial Phase III study, Clene would ex­pect to test the drug on top of stan­dard of care and will look to use the mMS­FC as a pri­ma­ry end­point, ex­ec­u­tives said on the in­vestor call. That would be a nov­el pri­ma­ry end­point, and the com­pa­ny said it has yet to re­view the end­point with the FDA.

The drug pre­vi­ous­ly failed a mid-stage test in pa­tients with ALS, but the biotech fol­lowed up that Phase II flop with open-la­bel sur­vival da­ta show­ing the drug de­creased risk of death.

Clene con­tin­ued with its ALS pro­gram by in­clud­ing CNM-Au8 in a plat­form study with oth­er in­ves­ti­ga­tion­al ther­a­pies from UCB, Bio­haven, Prile­nia Ther­a­peu­tics and See­los Ther­a­peu­tics. Topline re­sults from that study, the Har­vard Mass Gen­er­al-run HEALEY ALS, will read out this quar­ter. Those da­ta could sup­port an NDA sub­mis­sion in the first half of next year, the biotech said.

Al­so this quar­ter, Clene ex­pects to re­port topline da­ta from a Phase II study of its drug CNM-ZnAg in Brazil­ian pa­tients with acute­ly symp­to­matic Covid-19 who are not hos­pi­tal­ized.

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

Roger Perl­mut­ter lines up deals, fresh fund­ing at Eikon; Sec­ond RSV vac­cine ap­proved; Sev­er­al biotechs flash­ing red; 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.

As you come back to our website this weekend for ASCO news, don’t forget to check out our updated event lineup at BIO, which will cover everything from the current state of VC investing in biotech to top pharma R&D chiefs discussing how to make pipeline decisions.

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Full TIG­IT da­ta from Gilead, Ar­cus show low­er PFS rates than De­cem­ber read­out: #AS­CO23

CHICAGO — Gilead and Arcus unveiled a fuller snapshot of a Phase II study testing their experimental cancer immunotherapy combo that showed lower progression-free survival rates than its previous update, results that are likely to spark further debate over the closely-watched clinical trial.

Last December, the anti-TIGIT/anti-PD-L1 combo, positioned as a first-line treatment for non-small cell lung cancer, recorded data that drew mixed reactions. The latest analysis, presented Saturday afternoon at ASCO, included only a handful more patients than the previous update, but PFS rates fell — in one cohort by nearly three months.

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Bris­tol My­er­s' Op­di­vo keeps can­cer at bay in more lym­phoma pa­tients than Seagen's Ad­cetris in PhI­II: #AS­CO23

CHICAGO — In a study pitting Seagen’s Adcetris against Bristol Myers Squibb’s Opdivo in newly diagnosed patients with advanced classic Hodgkin lymphoma, a greater proportion of those who received Opdivo saw no cancer growth at one year compared to those who got Adcetris.

In addition, patients in the Opdivo arm of the Phase III trial reported reduced toxicities, according to lead investigator Alex Herrera, a hematologist-oncologist at City of Hope’s cancer cancer in Duarte, CA. Notably, the trial included more than 200 children across both arms. Generally, more than half of children with advanced Hodgkin lymphoma receive radiation therapy, but in this trial, dubbed SWOG S1826, only a handful of patients in the two arms received radiotherapy, sparing many children from long-term side effects of radiation.

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Servi­er’s vo­rasi­denib stalls pro­gres­sion of brain can­cer by 61% in piv­otal PhI­II IN­DI­GO study: #AS­CO23

An experimental pill from Servier Pharmaceuticals showed potentially practice-changing results in a narrow group of brain cancer patients, cutting the risk of their cancers progressing by 61%, according to a late-stage clinical trial.

The drug, vorasidenib, is a precision medicine that only works in certain people whose cancer carries mutations in one of two genes called IDH1/2. Doctors hope that the therapy will delay the need for chemotherapy or radiation, which are often used to combat relapses in patients who’ve previously undergone surgery to remove brain tumors.

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Peter van de Sande, Synaffix CEO

Lon­za shells out $107M cash to snap up Synaf­fix and its ADC plat­form

After lining up a string of partnerships over the years, Dutch antibody-drug conjugate specialist Synaffix has found a new home: Lonza, the contract development and manufacturing giant.

Lonza is paying about $107 million (€100 million) in cash to acquire Synaffix, with up to $64 million (€60 million) in “additional performance-based consideration” on the table. Synaffix’s ADC tech platform will now become part of Lonza’s offering for biopharma clients, lending its bioconjugate technologies to not just ADCs but also targeted gene therapy, immune cell engagers and other applications.

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As­traZeneca tri­al shows mod­est ben­e­fit in ovar­i­an can­cer, but doc­tors say it's hard to ap­ply find­ings: #AS­CO23

CHICAGO — Adding AstraZeneca’s Imfinzi and Lynparza to the treatment regimen for patients with advanced ovarian cancer and no BRCA mutation extended progression-free survival (PFS) by five months, according to interim data released at the ASCO annual meeting Saturday morning.

However, the design of the Phase III study obscures how much Imfinzi is contributing to the PFS extension, doctors said, making it difficult to apply the findings to clinical practice.

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Keytru­da be­fore and af­ter lung can­cer surgery cuts re­lapse risk by 42%, but doesn’t im­prove sur­vival: #AS­CO23

CHICAGO — Merck has found partial success with its latest effort to more aggressively treat earlier stages of lung cancer.

On Saturday the pharma giant announced results from a large trial in which patients received Merck’s immunotherapy Keytruda plus chemotherapy before surgeons removed their tumors, followed by another course of Keytruda afterward.

The Phase III study, called KEYNOTE-671, enrolled 800 people with the early stages of the most common kind of lung cancer: non-small cell lung cancer, or NSCLC. Everyone got chemo before surgery, and half also got Keytruda before and after. At two years, 62.4% of those who got Keytruda kept their cancer at bay, compared to 40.6% who got a placebo.

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Grail’s blood test charts path for di­ag­nos­ing pa­tients sus­pect­ed of hav­ing can­cer in large study: #AS­CO23

Grail’s vision is simple but bold. The blood testing company has long held that people are often diagnosed with cancer too late. If seemingly healthy people were screened for early signs of the disease before symptoms appear, they may be able to get more effective treatments that nip cancer in the bud.

That premise is the basis of Grail’s commercial blood test, Galleri, which searches for the genetic fingerprints of cancer in the blood. The test, launched in 2021, reaped $55 million in sales last year, but now the company is setting its sights on a new market: patients suspected of having cancer due to symptoms such as abdominal pain, rectal bleeding or unexplained weight loss. Rather than administering expensive scans or conducting invasive biopsies right away, Grail hopes doctors will consider a simple blood test.

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