Tril­li­um is hunt­ing gi­ants with its an­ti-CD47 drug, but ques­tions over a high-dose so­lo reg­i­men still linger

CD47 play­er Tril­li­um Ther­a­peu­tics re­leased a new slate of da­ta for two of its ex­per­i­men­tal can­cer drugs on Wednes­day, up­dat­ing pre­vi­ous­ly re­leased re­sults from last win­ter’s ASH con­fer­ence. But even though high­er dos­es of the pro­grams were ad­min­is­tered since then, the over­all re­sponse rates stayed rough­ly the same.

As of the new April 12 da­ta cut­off for the lead TTI-622 pro­gram, 9 of 27 evalu­able pa­tients with re­lapsed or re­frac­to­ry lym­phoma record­ed an ob­jec­tive re­sponse, good for a 33% ORR. That rate fell slight­ly from the ASH da­ta cut­off, where 6 of 17 evalu­able pa­tients saw re­spons­es, or 35%. One new com­plete re­sponse and two new par­tial re­spons­es were ob­served at the two high­est dos­es since the ASH up­date, Tril­li­um said.

The com­pa­ny is still wait­ing to col­lect da­ta from three more pa­tients at the high dose lev­el as well, so fi­nal re­sults of the study could change fur­ther.

Jan Skvar­ka

In an in­ter­view with End­points News, CEO Jan Skvar­ka said he isn’t con­cerned about the dif­fer­ence. He point­ed out that there’s no sta­tis­ti­cal dif­fer­ence be­tween the 33% and 35% fig­ures, as­sert­ing 33% re­mains a “very mean­ing­ful num­ber.” Skvar­ka con­tex­tu­al­ized TTI-622’s re­sponse rate by com­par­ing it with Mer­ck’s Keytru­da, say­ing that among its 19 in­di­ca­tions it typ­i­cal­ly sees rates be­tween 15% and 40%.

TTI-622 al­so put forth the high­est rate among an­ti-CD47 monother­a­py pro­grams, Skvar­ka as­sert­ed, a key dif­fer­en­ti­at­ing fac­tor from oth­er play­ers in the field us­ing com­bi­na­tion ther­a­pies.

“It’s a lit­tle bit fuzzy with dif­fer­ent in­di­ca­tions and so on, but nev­er­the­less it is the high­est re­sponse rate ob­served in the field,” Skvar­ka told End­points.

Dur­ing the com­pa­ny’s R&D day Wednes­day, Tril­li­um con­trast­ed their monother­a­py rates with some com­peti­tors in a pre­sen­ta­tion deck. There was the Gilead can­di­date ma­grolimab, ac­quired in the March 2020 buy­out of Forty Sev­en, as well as an ALX On­col­o­gy pro­gram called ALX148. Tril­li­um said its 33% ORR across all dos­es and test­ed lym­phomas proved fa­vor­able to a ma­grolimab ORR of 10% in acute myeloid leukemia and myelodys­plas­tic syn­drome, da­ta Tril­li­um pulled from Forty Sev­en’s AS­CO pre­sen­ta­tion in 2019.

Ad­di­tion­al­ly, the ALX can­di­date reg­is­tered no re­spons­es as of its own 2018 AS­CO up­date in sol­id tu­mors. And Tril­li­um fur­ther point­ed out that TTI-622 re­sponse rates as a monother­a­py in re­lapsed and re­frac­to­ry DL­B­CL (27%) stood up well to a ma­grolimab plus Rit­ux­an com­bo (36%) and ALX148/Rit­ux­an study (18% and 33% at two dosages) in the same field.

Skvar­ka read­i­ly con­ced­ed that no head-to-head da­ta ex­ist to di­rect­ly com­pare these pro­grams. But he of­fered that once Tril­li­um be­gins test­ing TTI-622 in com­bi­na­tion with chemother­a­py, mon­o­clon­al an­ti­bod­ies and PD-1 in­hibitors, the pro­gram is hop­ing to see even bet­ter re­spons­es than its 33% re­leased Wednes­day.

“The num­bers you see from the monother­a­py drug, these are our num­bers, they’re not com­ing from some com­bi­na­tion agent,” Skvar­ka said. “What you see are our re­sponse rates, but more im­por­tant­ly it’s the foun­da­tion of our next steps.”

With that strat­e­gy comes an ag­gres­sive clin­i­cal tri­als port­fo­lio, which Tril­li­um an­nounced Wednes­day will span sev­en dif­fer­ent in­di­ca­tions in­clud­ing three in sol­id tu­mors. The com­pa­ny plans to launch each of these stud­ies over the next 12 months, look­ing to com­bine TTI-622 with oth­er agents in p53 mu­tant AML pa­tients, plat­inum-re­sis­tant ovar­i­an can­cer and DL­B­CL, among oth­ers.

The high­est dose test­ed in the proof-of-con­cept study was 18 mg/kg, and the dose be­ing ad­vanced in­to the new tri­als is 8 mg/kg.

Tril­li­um’s pro­grams fo­cus on the pro­tein CD47, which tu­mors hi­jack in or­der to in­struct the im­mune sys­tem’s first re­spon­der-like macrophages to not de­stroy them — col­lo­qui­al­ly known as the “don’t eat me” sig­nal. Block­ing CD47, re­searchers have rea­soned, could the­o­ret­i­cal­ly get the im­mune cells to at­tack the can­cer in the way they’re sup­posed to.

The space got a huge boost from Gilead’s ac­qui­si­tion of Forty Sev­en for near­ly $5 bil­lion. Found­ed by Stan­ford stem cell pi­o­neer Irv Weiss­man, the sub­sidiary has fo­cused the ma­jor­i­ty of its ef­forts on ma­grolimab and earned a break­through ther­a­py des­ig­na­tion for myelodys­plas­tic syn­drome last Sep­tem­ber.

In its most re­cent da­ta up­date from last De­cem­ber, ma­grolimab saw progress in a Phase Ib tri­al for first-line AML. Among 43 evalu­able pa­tients treat­ed with ma­grolimab plus azac­i­ti­dine chemother­a­py, 27 saw at least a par­tial re­sponse. That reg­is­tered as a 63% ORR.

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

Paul Hudson (Getty Images)

Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

In­cyte keeps rolling on top­i­cal cream for JAK in­hibitor, pass­ing two PhI­II tests in vi­tili­go

As Incyte prepares to potentially hit the market with a topical formulation of its cash cow ruxolitinib in atopic dermatitis, the Wilmington, DE-based company is beefing up its data package for another indication: vitiligo.

Incyte released Phase III results from two of its clinical vitiligo programs Monday morning, saying both studies met their primary endpoints of patients achieving at least 75% improvement from baseline in repigmentation of the face. The data will likely lead Incyte to ask for approval in both the US and Europe for those older than 12 before the end of the year.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.

Days ahead of Am­gen split, Cy­to­ki­net­ics reads out post-hoc da­ta sug­gest­ing heart drug works bet­ter in sick­er pa­tients — but can the CEO win over skep­tics?

While Cytokinetics’ heart drug technically met its primary endpoint back in November, it missed a key secondary endpoint — reduction in cardiovascular death — which eventually cost the company two partnerships. Now the team is back with data suggesting the drug works better in sicker patients, and it’s planning a trip to the FDA.

In a post-hoc analysis, which can be a very difficult sale at the FDA, Cytokinetics separated patients from the Phase III GALACTIC-HF study into four quartiles based on ejection fraction, a measurement of how well the left ventricle pumps blood with each heartbeat. Patients in the lower two quartiles — those with an EF of 22% or lower, and between 29% to 32% — saw a 15% and 17% relative risk reduction of heart failure events and cardiovascular death combined, Cytokinetics reported at ACC. No difference was seen in the upper two quartiles.

Neil Desai, Aadi Bioscience CEO (Specialised Therapeutics via YouTube)

Patrick Soon-Sh­iong's for­mer chief sci­en­tist takes can­cer com­pa­ny pub­lic in $155M re­verse merg­er

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

SPACs have become the preferred fast track for public markets over the past year, but apparently there’s still room for a good, old-fashioned reverse merger.

Cancer-focused Aadi Bioscience announced Monday that they would merge with the struggling public biotech Aerpio Pharmaceuticals. To go along with the merger, Aadi raised $155 million from private investors to commercialize their lead drug, Fyarro, which is now sitting before the FDA. Acuta Capital Partners and KVP Capital led the round.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 105,400+ biopharma pros reading Endpoints daily — and it's free.