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.

Charles Baum, Mirati CEO

Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Retrophin beefs up the rare dis­ease drug pipeline with a $517M buy­out deal

A little more than a year after Retrophin conceded the complete failure of a drug co-invented by company founder Martin Shkreli, the biotech is beefing up its rare disease pipeline through a $517 million buyout deal — fronted with $90 million in cash.

After the bell sounded Thursday, Retrophin $RTRX put out word that it’s acquiring the low-profile biotech Orphan Technologies. The buyout gives them an enzyme replacement therapy called OT-58 for the treatment of classical homocystinuria, a rare disease that is triggered by insufficient levels of an enzyme called cystathionine beta synthase.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Pfiz­er scoops up an an­tibi­ot­ic in rare M&A deal, bag­ging a vir­tu­al start­up op­er­at­ing on a shoe­string bud­get

Pfizer is stepping up with a rare antibiotics buyout deal today, grabbing Palo Alto, CA-based Arixa Pharmaceuticals in a bid to add a new oral version of avibactam, a beta lactamase inhibitor — or BLI — approved back in 2015 as part of the IV treatment Avycaz.

The Arixa acquisition follows some encouraging Phase I responses demonstrating that 60% to 80% of the oral drug is absorbed into the bloodstream. Only 7% of the IV version is absorbed orally, far below the 30% threshold Arixa has pointed to as a therapeutic threshold. The buyout gives Pfizer’s hospital group a line on a new oral combo with antibiotics like ceftibuten to go after drug-resistant cases of urinary tract infections and other ailments.

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