An­oth­er mega-start­up: Chi­na in­vestors back TCR2's $125M cash round to fu­el a pre­clin­i­cal as­sault on sol­id tu­mors

Gar­ry Men­zel

In yet an­oth­er dis­play of biotech’s bold fundrais­ing en­vi­ron­ment right now, a Cam­bridge, MA-based start­up with a hand­ful of pre­clin­i­cal can­cer drugs in its pipeline has scored a $125 mil­lion mega-round — with all of the cash in the bank.

TCR2 Ther­a­peu­tics tells me they want­ed flex­i­bil­i­ty to pur­sue “mul­ti­ple pro­grams in mul­ti­ple for­mats,” which re­quires a sig­nif­i­cant amount of cash on hand. When peo­ple get hyped about mega-rounds, sober­ing re­al­ists will al­ways point out how mega-rounds are usu­al­ly tranched. That means the cash is gat­ed, and ac­cess to that cash is de­pen­dent on the start­up meet­ing cer­tain mile­stones.

This arrange­ment pro­vides some pro­tec­tion for cau­tious in­vestors, and is com­mon­place con­sid­er­ing this in­dus­try’s fail­ure rate. In­vestors in this case, how­ev­er, ap­pear to have thrown that cau­tion to the wind, bank­ing on TCR2’s abil­i­ty to pro­vide a re­turn one way or an­oth­er.

“All the mon­ey ar­rives in the bank on day one,” said Gar­ry Men­zel, CEO at TCR2.

How did the com­pa­ny get so much cash to play with? In part, they tapped flush in­vestor groups in Chi­na, one com­po­nent of a an in­creas­ing­ly pop­u­lar strate­gic move to fo­cus heav­i­ly in that mar­ket.

“There’s so much ac­tiv­i­ty in Chi­na right now,” Men­zel said. “There’s a tremen­dous amount of clin­i­cal ex­pe­ri­ence, good man­u­fac­tur­ing ca­pa­bil­i­ties, and it’s a big mar­ket.”

The mega-round was co-led by Shang­hai-based 6 Di­men­sions Cap­i­tal and Dal­las-based Cu­ra­tive Ven­tures. A long (long) list of new in­vestors and ex­ist­ing in­vestors joined in, in­clud­ing MPM Cap­i­tal (a ma­jor in­vestor in the on­col­o­gy space). Check out the com­pa­ny’s press re­lease for the full run­down.

Patrick Baeuer­le

What has these in­vestors so jazzed? TCR2 thinks it can lever­age the com­pa­ny’s un­der­stand­ing of the T cell re­cep­tor struc­ture to im­prove on how the body’s can­cer-fight­ing cells re­spond to dis­ease. The hope is to break down bar­ri­ers that have lim­it­ed ef­fi­ca­cy, ex­tend­ing im­muno-on­col­o­gy’s range in­to sol­id tu­mors.

The com­pa­ny was found­ed in 2015 by can­cer im­mu­nol­o­gist Patrick Baeuer­le, man­ag­ing di­rec­tor of MPM Cap­i­tal. You might rec­og­nize Baeuer­le as the for­mer CSO of Mi­cromet, which used an an­ti­body to redi­rect killer T cells to de­stroy tu­mor cells. Am­gen went on to ac­quire Mi­cromet in 2012 in a deal val­ued at $1 bil­lion-plus, bring­ing Baeuer­le on board to Am­gen to con­tin­ue work­ing on Blin­cy­to, an an­ti­body-based leukemia drug.

Now Baeuer­le sits on the board of TCR2, a com­pa­ny that wants to take im­muno-on­col­o­gy far past where CAR-Ts can go.

“There’s a lot of ex­cite­ment around CAR-T, and a lot of com­pa­nies in that space,” Men­zel said. “But CAR-T ran in­to a brick wall with sol­id tu­mors. There’s just been no ac­tiv­i­ty there.”

TCR² takes its name from T cell re­cep­tors (TCR), mol­e­cules on the sur­faces of im­mune cells that rec­og­nize a spe­cif­ic mol­e­c­u­lar tar­get, or anti­gen, and fo­cus an im­mune at­tack on cells with that tar­get. But CAR-T on­ly taps a part of a TCR’s full struc­ture.

“You can think of CAR-T as a piece of the TCR,” Men­zel said. “TCR has six sub­units, and CAR-T is one.”

Al­fon­so Quin­tás Car­dama

TCR² hopes to find a way to em­ploy the full TCR — a goal that com­pa­nies like blue­bird bio, Kite (Gilead), and GSK all have their eye on.  But TCR²’s CMO Al­fon­so Quin­tás Car­dama says the start­up has a game-chang­ing dif­fer­en­tia­tor. “We are ag­nos­tic to HLA. That’s the ad­van­tage of our plat­form over any oth­er TCR plat­form that re­quires spe­cif­ic HLA geno­typ­ing.”

TCR² has four pro­grams in the pipeline, all of which are tar­get­ing can­cers. Its lead in­ves­ti­ga­tion­al drug is called TC-210, a pre­clin­i­cal sol­id tu­mor ther­a­py that tar­gets mesothe­lin, an anti­gen present in sev­er­al types of can­cer. The com­pa­ny is hop­ing that drug can be used against ovar­i­an can­cer, mesothe­lioma, cholan­gio­car­ci­no­ma, and non-small cell lung can­cer (NSCLC).

Its sec­ond pro­gram is ba­si­cal­ly TC-210 with a PD1 switch at­tached, which the com­pa­ny hopes will make the ther­a­py more ef­fec­tive in lung can­cer pa­tients.

Its re­main­ing two pro­grams are still very ear­ly in their de­vel­op­ment, in ei­ther lead op­ti­miza­tion or dis­cov­ery stage. And TCR² isn’t say­ing much about ei­ther pro­gram, ex­cept that one is called Pro­gram X and the oth­er will take on blood can­cers.

Men­zel said the mas­sive Se­ries B round will like­ly take two pro­grams to proof-of-con­cept by 2021 and fi­nance an ex­pan­sion of the plat­form. TCR² plans to dou­ble its staff over the next year — from 30 to rough­ly 60 em­ploy­ees — all of whom will be work­ing out of a brand new fa­cil­i­ty in the heart of Kendall Square.

“You’ll see us grow­ing quite rapid­ly over the next year,” Men­zel says.

With $125 mil­lion in the bank, we wouldn’t ex­pect any less.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

Skin tu­mors in mice force Pro­tag­o­nist to halt lead pro­gram, crush­ing stock

Protagonist Therapeutics just can’t catch a break.

Six months after the Newark, CA-based biotech unveiled grand plans to launch its lead candidate for blood disorders into a Phase III trial, the FDA has slapped the program with a clinical hold. The halt — which applies to all trials involving the candidate, rusfertide — comes after skin tumors were discovered in mice treated with the drug, according to Protagonist.

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Chi­nese biotech Ever­est signs $550M+ li­cens­ing deal for BTK in­hibitors on heels of Covid-19 pact

Everest Medicines is on a roll with two licensing deals in one week.

The Shanghai-based biotech has paid Sinovent and SinoMab $12 million upfront for the rights to a BTK inhibitor for renal diseases, the company announced Thursday. The deal comes just days after Everest came away with rights to a Covid-19 vaccine in China, Taiwan, Singapore, Thailand and Indonesia.

Everest will pay Sinovent and SinoMab up to $549 million in milestone payments and royalties. The agreement includes tech transfer of Sinovent and SinoMab’s manufacturing process for the candidate, named XNW1011.