Roche/Ex­elix­is' Cotel­lic fiz­zles in piv­otal melanoma study

To lit­tle sur­prise, Ex­elix­is’ Cotel­lic — known chem­i­cal­ly as co­bime­tinib — in com­bi­na­tion with Roche’s Tecen­triq, has failed a late-stage study as a front­line treat­ment for pa­tients with a form of ad­vanced melanoma.

The Alame­da, Cal­i­for­nia-based com­pa­ny’s $EX­EL ki­nase in­hibitor — out-li­censed to Roche — was ap­proved in 2015 in com­bi­na­tion with the Swiss drug­mak­er’s Zelb­o­raf (ve­mu­rafenib) for pa­tients with BRAF V600E or V600K mu­ta­tion-pos­i­tive un­re­sectable or metasta­t­ic melanoma. Cotel­lic gen­er­at­ed rough­ly $61 mil­lion in glob­al sales last year.

Re­sults of the IM­spire170 study were dis­closed in a fil­ing on Thurs­day. Ex­elix­is said that Genen­tech (Roche), which spon­sored the study, had found that co­bime­tinib + Tecen­triq (ate­zolizum­ab) did not re­duce the risk of dis­ease pro­gres­sion or death com­pared to stan­dard-of-care Keytru­da, Mer­ck’s flag­ship PD-1 im­munother­a­py, in treat­ment-naïve pa­tients with BRAF V600 wild-type ad­vanced melanoma.

Last year, in the Phase III IM­blaze370 study, co­bime­tinib + Roche’s PD-L1 Tecen­triq failed to sig­nif­i­cant­ly help pa­tients with col­orec­tal can­cer live longer.

The like­li­hood of co­bime­tinib en­hanc­ing the im­pact of check­point in­hibitor ther­a­py in this melanoma tu­mor type (and oth­ers) was great­ly di­min­ished fol­low­ing last year’s dis­clo­sure of IM­blaze370 da­ta, Stifel’s Stephen Wil­ley wrote in a note. “We don’t view this news as the­sis-chang­ing (i.e. co­bime­tinib is not part of our, or any­one’s, near- or longer-term EX­EL the­sis) and con­tin­ue to view the dis­place­ment of 1L im­munother­a­py in this set­ting as un­like­ly.”

BMO Cap­i­tal Mar­ket’s George Farmer said the da­ta were in­con­se­quen­tial to his over­all Ex­elix­is in­vest­ment the­sis. “Phase 3 suc­cess (in the IM­spire170 study) would on­ly pro­vide up­side to ex­ist­ing co­bi sales, which was not fac­tored in­to our mod­el.”

An­oth­er co­bime­tinib late-stage tri­al, called IM­spire150 TRIL­O­GY, is ex­pect­ed to read out be­fore the end of this year. The study is eval­u­at­ing a triplet com­bi­na­tion of ve­mu­rafenib/co­bime­tinib/ate­zolizum­ab ver­sus the dou­blet com­bi­na­tion of ve­mu­rafenib/co­bime­tinib in pa­tients with first­line BRAF mu­tant ad­vanced melanoma. “(T)his triplet vs. dou­blet tri­al as more of a ‘check the box’ vs. an ‘ex­pand the mar­ket’ ex­er­cise and, like IM­spire170, don’t view IM­spire150 topline re­sults as a key cat­a­lyst for the stock,” Wil­ley wrote.

“We al­so be­lieve the on­go­ing eval­u­a­tion of oth­er triple-ther­a­py com­bi­na­tions (BRAF/MEK/PD-1) in 1L BRAF-mu­tant melanoma by oth­er, more-en­trenched com­peti­tors would like­ly keep any en­thu­si­asm re­lat­ed to a po­ten­tial TRIL­O­GY win ap­pro­pri­ate­ly mut­ed.”

Ex­elix­is’ for­tunes large­ly rest on the po­ten­tial of its TKI Cabome­tyx (cabozan­ti­nib) in the treat­ment of re­nal cell and he­pa­to­cel­lu­lar car­ci­no­ma. Top-line re­sults from the Check­mate-9ER tri­al, eval­u­at­ing cabozan­ti­nib plus Bris­tol-My­er’s $BMY PD-1 Op­di­vo, ver­sus Pfiz­er’s $PFE suni­tinib, are ex­pect­ed in the first half of 2020.

But com­pe­ti­tion is fierce. Mer­ck’s $MRK Keytru­da has been ap­proved in com­bi­na­tion with Pfiz­er’s TKI In­ly­ta for RCC pa­tients, as has Ger­man Mer­ck’s check­point in­hibitor, Baven­cio, (in com­bi­na­tion with In­ly­ta) for the pa­tient pop­u­la­tion.

So­cial im­age: Shut­ter­stock

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for Covid-19 vac­cine -- shares rock­et up

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

James Wilson, WuXi Global Forum at JPM20

FDA puts up a red light for Pas­sage Bio’s first gene ther­a­py pro­gram, de­lay­ing a pro­gram from James Wilson's group at Penn

Gene therapy pioneer James Wilson spearheaded animal studies demonstrating the potential of new treatments injected directly into the brain, looking to jumpstart a once-and-done fix for an extraordinarily rare disease called GM1 gangliosidosis in infants. His team at the University of Pennsylvania published their work on monkeys and handed it over to Passage Bio, a Wilson-inspired startup building a pipeline of gene therapies — with an IND for PBGM01 to lead the way.

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Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.