Michael Henderson, BridgeBio CBO

Bris­tol My­ers Squibb catch­es the SHP2 wave in a new col­lab­o­ra­tion deal with Bridge­Bio

Once con­sid­ered “un­drug­gable,” the phos­phatase en­zyme SHP2 has seen re­cent in­ter­est from a suite of Big Phar­mas, in­clud­ing As­traZeneca, Am­gen, No­var­tis and Mer­ck. Now Bris­tol My­ers Squibb is get­ting in on the ac­tion, with a deal to pair its PD-1 su­per­star Op­di­vo with Bridge­Bio’s SHP2 in­hibitor for dif­fi­cult-to-treat can­cers.

BMS and Bridge­Bio took the wraps off the non-ex­clu­sive, co-fund­ed col­lab­o­ra­tion ear­ly Tues­day morn­ing. The “cat­a­lyst,” Bridge­Bio CBO Michael Hen­der­son said, was last year’s vir­tu­al JP Mor­gan con­fer­ence, where the com­pa­nies met to dis­cuss ear­ly pre­clin­i­cal re­sults they were see­ing be­tween SHP2 and im­muno-on­col­o­gy ther­a­pies.

SHP2 is a phos­phatase that links growth fac­tor, cy­tokine and in­te­grin sig­nal­ing with the down­stream RAS/ERK MAPK path­way to reg­u­late cel­lu­lar pro­lif­er­a­tion and sur­vival. What does that mean? Over­ex­pres­sion of SHP2, for in­stance, has a down­stream sig­nal­ing ef­fect on tu­mor cell growth. It’s been sug­gest­ed that SHP2 has an ef­fect on the tu­mor mi­croen­vi­ron­ment, and sen­si­tiv­i­ty to im­muno-on­col­o­gy ther­a­py.

The part­ners will put Op­di­vo and BBP-398 — the SHP2 in­hibitor Bridge­Bio li­censed from MD An­der­son back in 2017 — in a Phase I/II study as a dou­blet ther­a­py, as well as a triplet ther­a­py along with a KRAS G12C in­hibitor in non-small cell lung can­cer pa­tients with KRAS mu­ta­tions.

Hen­der­son de­clined to say much about the fi­nan­cial terms of the deal, ex­cept that Bridge­Bio will spon­sor the study and BMS will pro­vide Op­di­vo. The part­ners will share costs for the com­bo tri­al.

Frank Mc­Cormick

“Can­cers that are dri­ven by hy­per­ac­tive MAPK sig­nal­ing, in­clud­ing cer­tain RAS mu­ta­tions such as KRASG12C, may be sen­si­tive to SHP2 in­hi­bi­tion,” Frank Mc­Cormick, chair­man of on­col­o­gy at Bridge­Bio, said in a state­ment. “With this col­lab­o­ra­tion, we hope to bet­ter elu­ci­date our SHP2 in­hibitor’s abil­i­ty to en­hance im­muno-on­col­o­gy and oth­er tar­get­ed ther­a­pies to po­ten­tial­ly pro­vide op­tions for pa­tients with dif­fi­cult-to-treat can­cers as quick­ly and safe­ly as pos­si­ble.”

Bridge­Bio is al­so test­ing the can­di­date as a monother­a­py, and the sci­en­tists ex­pect to nail down the rec­om­mend­ed Phase II dose in the next six to 12 months.

Rev­o­lu­tion Med­i­cines struck a deal back in Oc­to­ber to pair its lead SHP2 in­hibitor, RMC-4630, with As­traZeneca’s KRAS G12C pro­gram. That same can­di­date at­tract­ed Sanofi for a part­ner­ship back in 2018 that in­volved $50 mil­lion up­front, 80% of the R&D cost, and a swath of mile­stones adding up to $520 mil­lion. Tai­ho and As­tex grant­ed Mer­ck an ex­clu­sive li­cense to their joint SHP2 pro­gram in Jan­u­ary. And in April, Ana­vo Ther­a­peu­tics launched with $24 mil­lion in seed fund­ing to bust the doors on phos­phatases wide open.

“I think ear­ly on in the class, it’s too ear­ly to tell where the class is go­ing to end up, es­pe­cial­ly with such lim­it­ed da­ta that’s been re­leased,” Hen­der­son said. “We’re very ex­cit­ed to col­lab­o­rate with BMS on this.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a specific market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,800+ biopharma pros reading Endpoints daily — and it's free.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,800+ biopharma pros reading Endpoints daily — and it's free.

Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Vicente Anido (University of West Virginia via YouTube)

Aerie fires CEO af­ter lead pro­gram flop, com­ments about pri­ma­ry end­points be­ing 'not re­quired'

Aerie Pharmaceuticals CEO Vicente Anido has left the company less than a week after trying to chart a Phase III study in the wake of a serious Phase IIb flop.

Anido’s last day at Aerie was Friday, the biotech announced in a news release Tuesday morning, and Benjamin McGraw is taking his place in an interim role. The now former CEO was terminated without cause, according to an SEC filing.

The board has started looking for a full-time chief to take his place.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,800+ biopharma pros reading Endpoints daily — and it's free.