David Baltimore (Vincent Yu/AP Images)

No­bel lau­re­ate David Bal­ti­more throws his weight be­hind I/O start­up look­ing to craft off-the-shelf CAR ther­a­pies

In the in­su­lar world of biotech, names mat­ter — and no names shine brighter than those lu­mi­nar­ies with a No­bel Prize on their record. Now, a Los An­ge­les start­up work­ing at the fur­thest fron­tiers of cell ther­a­peu­tics is stand­ing on the shoul­ders of a lau­re­ate of its own and look­ing to rewrite the fight against sol­id tu­mors.

On Tues­day, Ap­pia Bio launched with $52 mil­lion in Se­ries A fi­nanc­ing led by 8VC and a plat­form fo­cused on what are called in­vari­ant nat­ur­al killer T cells (iNKT), an ex­treme­ly rare im­mune cell the biotech hopes to reengi­neer to bust ma­lig­nant tu­mors through a “best of both worlds” at­tack plan, the com­pa­ny said.

Ap­pia’s work is found­ed on sci­ence from UCLA pro­fes­sor Lili Yang along­side a man­age­ment team of Kite Phar­ma vet­er­ans and a first-time CEO all grav­i­tat­ing around one man — David Bal­ti­more, the 83-year-old No­bel lau­re­ate and pres­i­dent emer­i­tus at Cal­Tech.

Bal­ti­more’s work on hu­man virus­es earned him the prize for phys­i­ol­o­gy and med­i­cine back in 1975, and since then his labs have most­ly been in­volved in non-trans­la­tion­al bench sci­ence. But in re­cent years, his Cal­Tech re­search team has propped up a trans­la­tion­al wing fo­cus­ing on the use of AAV-based gene trans­fer for use in stem cells.

Lili Yang

Yang, a 13-year vet­er­an of Bal­ti­more’s lab who moved up from grad­u­ate re­search as­sis­tant to post­doc to lead sci­en­tist on en­gi­neered im­mu­ni­ty, moved to UCLA in 2013 as an as­sis­tant de­part­ment head in mi­cro­bi­ol­o­gy, im­munol­o­gy and mol­e­c­u­lar ge­net­ics, where she start­ed work­ing on the po­ten­tial for ther­a­peu­tic iNK­Ts in on­col­o­gy, this time us­ing lentivi­ral gene trans­fer in­stead of AAV. In Sep­tem­ber 2019, her team pub­lished in Cell Stem Cell proof of con­cept for an “off-the-shelf,” en­gi­neered iNKT pro­lif­er­at­ed in vi­vo through stem cells.

Af­ter show­ing some suc­cess in mice with­out any se­ri­ous safe­ty flags, Yang and col­lab­o­ra­tors Bal­ti­more and Pin Wang, a pro­fes­sor of chem­i­cal en­gi­neer­ing and ma­te­ri­als sci­ence and bio­med­ical en­gi­neer­ing at USC, saw a path to a po­ten­tial prod­uct and kick­start­ed Ap­pia last year.

The promise of an al­lo­gene­ic cell ther­a­py has been a hot area of in­vest­ment in re­cent years, but re­searchers have had a hard time show­ing that reengi­neered T cells that don’t come from pa­tients’ own bod­ies can pass the im­mune sys­tem with­out heinous side ef­fects. But with iNK­Ts, which co-ex­press NK and T cell mark­ers, the Ap­pia team thinks it can evade the graft vs. host dis­ease en­dem­ic to al­lo­gene­ic cell ther­a­pies and en­gi­neer mul­ti­ple routes of at­tack on tu­mors us­ing the in­nate and ac­tive im­mune sys­tem.

JJ Kang

Join­ing the sci­en­tif­ic brain­trust is JJ Kang, a for­mer part­ner at The Col­umn Group who re­ceived her doc­tor­ate in chem­i­cal bi­ol­o­gy at Cal­Tech be­fore a stint as pres­i­dent at Tenaya Ther­a­peu­tics from 2016 to 2018 — what she told End­points News was like “run­ning a com­pa­ny with train­ing wheels.” Bal­ti­more was in­stru­men­tal in in­tro­duc­ing Kang to the Col­umn team, and when she got the chance to head Ap­pia, she jumped.

“It’s so much about peo­ple and the way that things mesh to­geth­er,” she said. “In the aca­d­e­m­ic col­lab­o­ra­tion that led up to it, you al­ready had the founders that worked to­geth­er, and adding on the man­age­ment founders, we all kind of meshed well and it made sense to build a com­pa­ny.”

For Bal­ti­more, who helped Kang arrange the CEO role, he told End­points that de­spite her lack of ex­pe­ri­ence in im­munol­o­gy, Kang has tak­en to the plat­form and was ready to lead a biotech with big am­bi­tions.

“I think she’s in the per­fect po­si­tion to now move in­to a re­spon­si­ble man­age­r­i­al role,” Bal­ti­more said of Kang’s prepa­ra­tion for the job. “She has every oth­er form of ex­pe­ri­ence, she knows the peo­ple and the moves to get a com­pa­ny go­ing, and she’s re­al­ly de­vot­ed to the tech­nol­o­gy.”

The rest of the found­ing team is com­prised of Jeff Wiezorek, the for­mer head of cell ther­a­py de­vel­op­ment at Kite Phar­ma who will take on the CMO role, and Ed­mund Kim, Ap­pia’s chief op­er­at­ing of­fi­cer and for­mer VP of cor­po­rate de­vel­op­ment at Kite. Wiezorek ac­tu­al­ly shared a bench with Yang while at Cal­Tech — start­ing to see the bonds formed here? — while Kim is the odd man out look­ing to bring his ex­pe­ri­ence at a mar­ket­ed cell ther­a­py to bear at the fledg­ling firm.

Hav­ing that de­vel­op­ment ex­pe­ri­ence will bode well as the Ap­pia team hopes to trans­late its win­ning pre­clin­i­cal da­ta in­to a suc­cess­ful hu­man tri­al, which Kang said the com­pa­ny hopes to en­ter by late 2023. Bal­ti­more said the plat­form holds promise, but it’s still too ear­ly to say whether it will even­tu­al­ly prove ef­fec­tive.

“There’s a strong like­li­hood it will work, but you don’t know un­til you test it,” he said. “There will be sur­pris­es, there will be an­noy­ances, but I feel con­fi­dent that this is the right mo­ment to try.”

The Se­ries A was joined by Two Sig­ma Ven­tures among oth­ers, with par­tic­i­pa­tion from seed in­vestors Sher­pa Health­care Part­ners and Freeflow Ven­tures.

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

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What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

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Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

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David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

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FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

The IPO 4-1-1: Four fil­ings, a pric­ing and a with­draw­al head­line this week's Nas­daq ac­tion as raise ap­proach­es $7.5B

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

Another week, another horde of biotechs is doing the Nasdaq dance.

This week saw four companies file their SEC paperwork ahead of expected debuts, another hit Nasdaq on Friday and a sixth formally withdrew its bid to go public. Aerovate Therapeutics, Ocean Biomedical and Acumen Pharmaceuticals all penciled in initial raises of $100 million, while Dermata Therapeutics is estimating a modest $18 million raise.

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Keiichi Fukuda, Heartseed CEO

Fresh off $598M deal with No­vo Nordisk, a Japan­ese stem cell com­pa­ny is on its way to the clin­ic with a dif­fer­ent ap­proach to treat­ing heart fail­ure

A common approach to treating heart failure with induced pluripotent stem cells involves grafting sheets of cells onto the surface of the heart to improve vascularization and blood flow. It’s the easiest method of transplantation — but you run the risk of not making an electrical connection with the heart and the cells not synchronizing with the patient’s heart muscle.

So what if you could inject spherical clusters of heart cells directly into the heart muscle wall? For Heartseed, that’s now the $37 million question.

Ver­tex and CRISPR Ther­a­peu­tics un­veil more pos­i­tive gene ther­a­py da­ta, but busul­fan again casts a shad­ow over the field

Less than 12 hours after revealing a flop on its second shot for alpha-1 antitrypsin deficiency, Vertex plowed ahead with another data drop from its partnership with CRISPR Therapeutics. And though the topline proved positive, concerns over conditioning agents continue to linger over the collaboration, as well as the entire gene therapy space.

Presenting data from two trials at the European Hematology Association annual meeting, the pair announced that follow-up data of at least three months for 22 patients with genetic blood disorders indicated a “consistent and sustained” response to the experimental drug CTX001. All 15 patients with transfusion-dependent beta thalassemia did not need further blood transfusions and all seven with severe sickle cell disease were pain free, the biotechs announced.

Janet Woodcock, acting FDA commissioner, at Thursday's Senate Appropriations hearing (Bill Clark/CQ Roll Call via AP Images)

Sen­a­tors lam­bast new Alzheimer’s drug’s price but give Janet Wood­cock a free pass on the ap­proval de­ci­sion

Senate Finance Democrats took aim at Biogen’s pricey new Alzheimer’s drug on Thursday, but members on both sides of the aisle at a separate appropriations hearing didn’t question acting FDA commissioner Janet Woodcock on the approval.

“I was appalled that Biogen priced their Alzheimer’s drug approved by the FDA at $56,000 per year — I’m not going to debate whether this is effective or not, but it’s double the household median income for Michiganders over the age of 65,” Sen. Debbie Stabenow (D-MI) said at the finance hearing.