Dab­bling in CD47, Pfiz­er in­fus­es $25M in­to a biotech play­er tout­ing pos­i­tive monother­a­py da­ta

Pfiz­er is fol­low­ing Gilead, Ab­b­Vie, Boehringer and a string of biotech up­starts in­to the CD47 race, lin­ing up its own shots at the “don’t eat me” sig­nal that is shap­ing up to be the big can­cer check­point tar­get.

And it’s start­ing small.

Jan Skvar­ka

With $25 mil­lion in ini­tial in­vest­ment, Pfiz­er is stack­ing up about 2.3 mil­lion shares in Tril­li­um Ther­a­peu­tics $TRIL for $10.88 per share — a 15% pre­mi­um over its Fri­day close. In­vestors were quick to fol­low Pfiz­er’s lead, bid­ding up Tril­li­um’s shares 40% Wednes­day morn­ing.

For Tril­li­um, which has its roots in Cana­da but has branched out to Cam­bridge, MA, the deal al­lows it to re­tain full rights to its drugs while tap­ping in­to the ex­per­tise and re­sources from a phar­ma gi­ant. Jeff Set­tle­man, Pfiz­er’s CSO for on­col­o­gy R&D, is be­com­ing one of the first mem­bers of its sci­en­tif­ic ad­vi­so­ry board.

The phar­ma gi­ant’s in­vest­ment isn’t tied to any right of first re­fusal for part­ner­ships or buy­outs, CEO Jan Skvar­ka said in an in­vestor call that fol­lowed lat­er in the af­ter­noon. Those op­tions re­main wide open.

“These are very ex­cit­ing times for both the CD47 field and Tril­li­um Ther­a­peu­tics,” he de­clared ear­ly in the call.

Jeff Set­tle­man

Just days ago, Ab­b­Vie wa­gered $200 mil­lion in cash to li­cense glob­al rights to an an­ti-CD47 an­ti­body from Chi­na’s I-Mab, which con­cur­rent­ly raised a whop­ping $418 mil­lion from top in­vestors on both sides of the Pa­cif­ic. It in turn fol­lowed Gilead’s $4.9 bil­lion takeover of Forty Sev­en. The stakes have grown sig­nif­i­cant­ly since 2018, when Boehringer paid on­ly $37 mil­lion to team up with Sur­face On­col­o­gy.

So what ex­act­ly is Pfiz­er buy­ing in­to? Just be­fore the call the biotech of­fered an­oth­er slice of ear­ly hu­man da­ta for its two lead pro­grams, an up­date on its pre­sen­ta­tion at AS­CO about three months ago.

TTI-622, the SIR­Pa-IgG4 Fc fu­sion pro­tein that (like I-Mab’s can­di­date) promis­es to spare red blood cells, now has a 33% over­all re­sponse rate across the 0.8 to 9 mg/kg dose lev­els (6/18). At the 8 mg/kg lev­el in par­tic­u­lar, 3 out of 6 pa­tients ex­pe­ri­enced an ob­jec­tive re­sponse, trans­lat­ing to a stel­lar 50% ORR — for a heav­i­ly pre­treat­ed group with re­lapsed/re­frac­to­ry lym­phoma.

Bob Uger

Now that the safe­ty as­sess­ment for that high dose is com­plete, in­ves­ti­ga­tors are mov­ing on to the 12 mg/kg as the next step in their dose es­ca­la­tion study.

“Let me put this monother­a­py ac­tiv­i­ty da­ta in con­text of some of our CD47 com­peti­tor da­ta from their com­bi­na­tion stud­ies with rit­ux­imab,” Skvar­ka said. “[Gilead’s] ma­grolimab showed 36% ORR in re­lapsed/re­frac­to­ry DL­B­CL pa­tients, and it was at ma­grolimab’s full dose of 30 mg/kg in com­bi­na­tion with Rit­ux­an. Sim­i­lar­ly al­so ALX-148 showed 55% ORR at their full dose of 50 mg/kg and al­so in com­bi­na­tion with rit­ux­imab.”

While the CEO was care­ful to note that it’s not a head-to-head com­par­i­son, he saw an en­cour­ag­ing sign that TTI-622, with dose lev­els test­ed so far, al­ready has “com­pa­ra­ble” re­sults with ri­vals at their high­est dose in com­bi­na­tion stud­ies. At the same time, the re­sults show that “not all IgG4s are cre­at­ed equal,” as Tril­li­um’s da­ta are turn­ing out bet­ter than what com­men­ta­tors ex­pect­ed fol­low­ing Cel­gene’s ter­mi­na­tion of a Phase I study of its own IgG4 an­ti­body two years back.

That qual­i­fies as the “strongest monother­a­py da­ta shown by a CD47 tar­get­ing can­di­date” in the eyes of Cowen an­a­lyst Boris Peak­er, com­plete with an im­pres­sive safe­ty pro­file.

“We be­lieve that even if the high­er dose of 12 mg/kg is not tol­er­a­ble, the 50% ORR achieved at the 8mg/kg lev­el is suf­fi­cient to ad­vance this drug fur­ther,” he wrote.

Yap­ing Shou

It’s not nec­es­sar­i­ly that Tril­li­um plans to com­pete with a sin­gle agent; CSO Bob Uger list­ed an­ti-PD-(L)1 drugs, pro­tea­some in­hibitors, Darza­lex, Er­bitux and Folo­tyn as po­ten­tial pair­ings for dif­fer­ent in­di­ca­tions. But hav­ing sol­id monother­a­py da­ta as a foun­da­tion gives ex­ecs more con­fi­dence that their drug would do even bet­ter in com­bo.

On the safe­ty side, Tril­li­um dis­closed that one pa­tient ex­pe­ri­enced a Grade 4 ad­verse event, but CMO Yap­ing Shou ex­plained that the clas­si­fi­ca­tion had more to do with the in­ves­ti­ga­tor be­ing ex­tra-cau­tious amid Covid-19 and ad­min­is­ter­ing pro­phy­lac­tic platelet trans­fu­sion to the pa­tient than any symp­toms (there were none). That pa­tient was switched out of the 8 mg/kg dose but re­mains on drug.

Ex­ecs al­so re­port­ed on a sec­ond pro­gram — TTI-621, a fu­sion pro­tein with an IgG1 back­bone. The main pitch around this drug is that it can achieve big ef­fects with an ex­tra-low dose. Out of 6 evalu­able pa­tients in the 1 mg/kg co­hort, there was one par­tial re­sponse and one cu­ta­neous T-cell lym­phoma pa­tient who saw com­plete clear­ance of skin le­sions. Two were bridged to al­lo­gene­ic trans­plan­ta­tion.

Now that the 1.4 mg/kg dose has been deemed well-tol­er­at­ed among pa­tients with ad­vanced re­lapse/re­frac­to­ry blood can­cers, the next step is test­ing 2.0 mg/kg.

Tril­li­um plans to con­tin­ue eval­u­at­ing both pro­grams to see if one stands out — but might just push both for­ward if they turn out to have dif­fer­ent ap­pli­ca­tions. Even­tu­al­ly it plans to get in­to sol­id tu­mors, a space Skvar­ka said Pfiz­er is very in­ter­est­ed in.

Be­fore the Pfiz­er in­vest­ment, the com­pa­ny had end­ed the sec­ond quar­ter with $130.8 mil­lion in cash and in­vest­ments, Peak­er not­ed, which was con­sid­ered suf­fi­cient to fund it in­to 2022.

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