Can tiny Mus­tang Bio com­pete on the CAR-T front with gi­ants like No­var­tis and Gilead? Man­ny Litch­man aims to find out

Now that No­var­tis and Gilead have picked up the first two ap­provals for CAR-T drugs, you can ex­pect to see ri­vals com­ing along who will probe for any weak­ness­es in their ap­proach, look­ing to com­pete on the next wave of per­son­al­ized cell ther­a­pies head­ed through the clin­ic.

The small crew at Mus­tang Bio — $MBIO, up 11% to­day — has some big am­bi­tions on that score, and to­day they’re adding some man­u­fac­tur­ing ca­pac­i­ty that the com­pa­ny be­lieves will be cen­tral to its abil­i­ty to even­tu­al­ly com­pete with these two gi­ants.

Man­ny Litch­man

Mus­tang has inked a lease deal with the UMass Med­i­cine Sci­ence Park in Worces­ter, MA, where they ex­pect to be­gin pro­duc­tion of their CAR-Ts next year. And they’ll be aim­ing to make these cell ther­a­pies for ear­ly-stage stud­ies for glioblas­toma and acute myeloid leukemia and a grow­ing sta­ble of pre­clin­i­cal ef­forts.

Look­ing for com­pet­i­tive ad­van­tages at this stage of the game will re­ly quite a lot on a “more stream­lined, more cost ef­fec­tive man­u­fac­tur­ing ap­proach,” CEO Man­ny Litch­man tells me. “Every­thing re­al­ly has cost in mind,” he adds, siz­ing up the first two ther­a­pies that come with hefty six-fig­ure price tags.

“Look in the black box of man­u­fac­tur­ing,” he says, and you can see “dozens of pa­ra­me­ters that can vary.”

There’s more reengi­neer­ing work to be done to make CAR-Ts bet­ter at com­bat­ting can­cers like glioblas­toma and AML, he adds. In­ves­ti­ga­tors, for ex­am­ple, have been bal­anc­ing the im­pact of quick ver­sus slow­er ac­tion of the ther­a­peu­tic — slow­er ac­tion ap­pears to be more durable — along with a mul­ti­tude of com­bi­na­tion ap­proach­es that need to be ex­plored.

There’s enough po­ten­tial in these new ap­proach­es to of­fer an open­ing for a com­pa­ny like Mus­tang to step in and ex­ploit new op­por­tu­ni­ties, he be­lieves.

Litch­man left the helm at Arv­inas, a pro­tein degra­da­tion biotech spun out of the lab of Yale’s Craig Crews, to take the lunge at CAR-T. It’s a field he knows some­thing about. As for­mer head of on­col­o­gy BD at No­var­tis, Litch­man was present at the cre­ation of the Penn/No­var­tis deal that set the phar­ma gi­ant down the path to­ward an his­toric CAR-T ap­proval. He was pro­gram head of CTL019 for awhile. And he’s fol­low­ing in much the same path that the pi­o­neers — along with Kite and Juno — did, let­ting the sci­en­tif­ic founders do the ear­ly-stage re­search work that will be used to set up the fast-paced piv­otal de­vel­op­ment pro­grams to come.

Stephen For­man

In Mus­tang’s case, that in­volves Stephen For­man’s lab­o­ra­to­ry at City of Hope Na­tion­al Med­ical Cen­ter and top re­searchers at the Fred Hutchin­son Can­cer Re­search Cen­ter, where Oliv­er Press and Bri­an Till have been build­ing a T cell ther­a­py which ex­press­es a CD20-spe­cif­ic chimeric anti­gen re­cep­tor. That work has ex­pand­ed Mus­tang’s pipeline to 6 clin­i­cal and pre­clin­i­cal ef­forts.

The Cal­i­for­nia In­sti­tute for Re­gen­er­a­tive Med­i­cine, rest­less­ly look­ing to make a clin­i­cal mark af­ter years in­vest­ing in labs, just days ago pro­vid­ed a $12.8 mil­lion grant to the City of Hope for the Phase I glioblas­toma study. And that comes on top of a $94.5 mil­lion raise in Feb­ru­ary from a pri­vate place­ment arranged by its par­ent com­pa­ny Fortress, which is build­ing a port­fo­lio of biotechs.

Try­ing to leapfrog in­to a clin­i­cal ri­val­ry in a com­plex are­na like this will cost much, much more than that. And Litch­man tells me he has plans to raise some­where be­tween $60 mil­lion and $100 mil­lion more next year.

Right now, Mus­tang has 5 full timers, a tiny boat­load of staffers com­pared to the jug­ger­nauts crewed by No­var­tis and Gilead’s Kite. Juno al­so has a much larg­er op­er­a­tion look­ing to make a come­back af­ter their lead ther­a­py was de­stroyed by its lethal tox­i­c­i­ty. But Litch­man plans to up that to about 20 over the next year, while the in­de­pen­dent sci­en­tists con­tin­ue to do the heavy lift­ing in the ear­ly stud­ies.

This is one race that Litch­man says is still very much just be­gin­ning. And it won’t be dom­i­nat­ed by a hand­ful of lead­ers.

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Turn­ing the cor­ner on treat­ing the root cause of sick­le cell dis­ease

Early in my career, as a medical resident, I saw first-hand the enormous challenges faced by children and adults with sickle cell disease (SCD), a genetic blood disorder that historically has lacked adequate treatment options. People living with this life-long disease are mainly those with ancestors from sub-Saharan Africa, as well as people of Hispanic, South Asian, Southern European and Middle Eastern descent. These patients suffer from devastating physical symptoms, including progressive, eventually fatal, organ damage and excruciating pain. In addition, they encounter emotional, mental and social burdens – non-physical aspects of living with SCD that also take a serious toll on patients and their caregivers.

Rev­o­lu­tion Med shoots for $100M+ IPO — and di­vulges some se­crets about that Warp Dri­ve buy­out

Biotech investors who like to wager on the race to the front of the KRAS market now have a new team to consider.

Revolution Medicines, which extended its reach on RAS with a deal to acquire Warp Drive Bio about 18 months ago, filed their S-1 in search of $100 million-plus. And they gave up a few secrets in the process.

The main clinical claim to fame that Revolution has centers on the SHP2 inhibitor RMC-4630, partnered with Sanofi back in the summer of 2018 — just after John Reed was named the incoming R&D chief. We already knew that the pharma giant handed over $50 million in cash plus a commitment of hundreds of millions more to align itself with Revolution as it makes a fresh foray into oncology. Now we know that Sanofi is also footing 80% of Revolution’s R&D bill on the program, while setting up a smorgasbord of $235 million in development milestones and $285 million in commercial bonuses.

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Olivier Brandicourt, AP Images

#JPM20 ex­clu­sive: Olivi­er Brandi­court fol­lows the Big Phar­ma CEO path to pri­vate eq­ui­ty, join­ing Black­stone ahead of a mam­moth fund de­but

Nick Galakatos Blackstone

Seven months after Olivier Brandicourt’s surprise “early retirement” from Sanofi, he’s back in the game, this time taking meetings at JP Morgan to discuss his new role at Blackstone, where he’s quietly begun work with Nick Galakatos and the life sciences crew.

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Video Re­play: End­points at #JPM20 — news­mak­ers on deal­mak­ing, pric­ing and man­u­fac­tur­ing

On Monday, we held our fourth annual #JPM event — and the team hit a key milestone that I’d like to share with the entire Endpoints News audience: We live-streamed the conversation and had nearly triple the number of executives watching online than we had in the sold-out crowd of 320.

For a media company on a mission to connect the biopharma world in bigger and better ways, we’re proud of how we were able to extend the reach of our franchise event. Paid subscribers were given access to the stream in real time, and now, two days later, we’re opening it up to everyone in this post.

Endpoints@JPM: (left to right) Steve Pearson, Nick Leschly, Bari Talente, Stephen Ubl, John Carroll

#JPM20: 'The NPV is al­ways wrong.' Take­da preps an­oth­er spin­out — this time on psych

Editor’s Note: Endpoints News is reporting live from #JPM20 after kicking things off with an action-packed event, which you can replay here. What follows is a stream of tidbits we have collected while wandering around Union Square in San Francisco. Check back in throughout the week for updates by John Carroll and Jason Mast.

SAN FRANCISCO — A year ago Takeda CEO Christophe Weber and R&D chief Andy Plump arrived at JP Morgan right on the heels of closing their big Shire buyout. Now they’re back after shaking up the portfolio, boosting R&D spending by about 50% to $4.5 billion and adjusting the pipeline — a task which isn’t quite finished yet.

Nick Leschly at Endpoints News' panel at the 2020 JP Morgan Healthcare Conference. Credit: Jeff Rumans

At #JPM20, two CEOs, two rad­i­cal­ly dif­fer­ent ther­a­pies, and a fight to chase down sick­le cell

SAN FRANCISCO – Few CEOs tell a story better than bluebird’s Nick Leschly.

He cuts a Jeff Bezos figure on stage at the Colonial Room, the JP Morgan presentation hall for A-list biotechs: lean and bald, fast-talking and vest-wearing. He explains in simple language, apologizing when he has to brush on the data. It helps that he has a good story to tell.

“We treated them one time,” Leschly tells a packed crowd, gesturing to the slide behind him. “Look what happened.”

The slide shows 9 horizontal bars studded with diamonds. Each bar, he explained, represented a sickle cell patient, and each diamond represented a severe medical event, such as a pain crisis. The diamonds stud one side – before the therapy – and vanish on the other, afterward.

“A 99% reduction in these events — this is a functional cure for sickle cell disease,” Leschly says. “This is unprecedented data.”

Upstairs and an hour later, Ted Love stands before a narrow conference room in his suit and polka-dot tie. Love, the CEO of Global Blood Therapeutics, is a 60-year-old physician. His voice trails off at the end of sentences, and the story he tells is less compelling. There are no cured patients.

“This is the first drug that addresses the root cause of sickle cell disease,” Love says, speaking in front of a slide showing a white pill bottle for GBT’s new drug Oxbryta. “Right in the label, it says that this drug inhibits polymerization.”

In the 60 years after scientists discovered the cause of sickle cell, almost no treatments emerged, even as the condition debilitated hundreds of thousands of Americans, most of them black or Hispanic. But the last few years have seen a resurgence of interest as new technologies have made the disease seem newly beatable.

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Neon Ther­a­peu­tics makes one last re­treat, sell­ing it­self cheap in a bar­gain base­ment M&A deal

Crushed by weak data for what had been their lead drug, Neon Therapeutics is being bought for parts this morning.

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Mark Pruzanski

#JPM20: Af­ter a year of NASH col­laps­es, all eyes on two biotechs

SAN FRANCISCO – It’s not quite Dewey defeats Truman, but Goldman Sachs calling 2019 “The Year of NASH” may well go down in the annals of worst biotech predictions.

Goldman Sachs slapped the label on weeks before 2019’s JP Morgan conference, projecting that long-discussed treatments for the obesity-driven condition suspected to lurk in millions of Americans would begin to bear fruit and investors would move accordingly. That did not quite happen.

“If you look at 2019, it was just a string of disappointing news,” Pascal Prigent, CEO of NASH-focused biotech Genfit, told Endpoints News in an interview.

The Year of NASH, or nonalcoholic steatohepatitis, became a year of NASH failures. Gilead failed two large Phase III trials. CymaBay went from a $1 billion company to a $100 million company after they found their drug was killing patients’ liver cells. Cirius withdrew an $86 million IPO bid after a disastrous readout. Industry-wide, there were few acqusitions in a market often projected to be worth $35 billion.

Gilead, after dominating the NASH discussion at the 2019 JPM, gave one quick mention to the program in their 2020 presentation before pivoting to other drugs.

“As promising as some of the mechanisms looked in earlier stages, when push comes to shove in large study settings, they just haven’t proven out,” Mark Pruzanski, CEO of the NASH-focused biotech Intercept, told Endpoints in an interview.

As biotech turns from 2019, the failures have refocused eyes away from Gilead and back toward two startups, both facing key events in the coming months: Intercept, which first alerted investors to NASH at JPM 2014, and the France-based Genfit.

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