Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

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The lat­est biotech-SPAC deal has ar­rived, and it’s danc­ing its way to Nas­daq to the tune of sev­er­al hun­dred mil­lion dol­lars.

Tan­go Ther­a­peu­tics and its CRISPR-fo­cused search for new can­cer genes is re­verse merg­ing with Box­er Cap­i­tal’s blank-check com­pa­ny, the biotech an­nounced Wednes­day morn­ing. With a spot­light on three lead pro­grams, Tan­go ex­pects to­tal pro­ceeds to equal about $353 mil­lion in the deal, which in­cludes the rough­ly $167 mil­lion held in the SPAC and an ad­di­tion­al $186 mil­lion in PIPE fi­nanc­ing.

CEO Bar­bara We­ber told End­points News that Tan­go had been plan­ning for a tra­di­tion­al IPO at some point this year, hav­ing re­cent­ly fin­ished non-deal road­shows with about 30 to 40 in­vestors. But they shift­ed gears when Box­er, who had pre­vi­ous­ly led the com­pa­ny’s Se­ries B in April 2020, ap­proached Tan­go ex­ecs with the SPAC idea.

“When we looked at the in­vestors that were in the SPAC, they were the same list of peo­ple that we had just spent two months talk­ing to,” We­ber told End­points. “We ac­tu­al­ly didn’t look at any oth­er SPACs; this was a spe­cif­ic de­ci­sion around the Box­er-spon­sored SPAC.”

Blank check com­pa­nies have tak­en Wall Street by storm, and the bio­phar­ma sec­tor has not been left out of the fun. Per an End­points News tal­ly, Tan­go is the fifth life sci­ences com­pa­ny to ride a SPAC to Nas­daq this year, fol­low­ing in the foot­steps of 23andMe, Se­ma4, So­ma­Log­ic and Bet­ter Ther­a­peu­tics.

That’s brought in a hefty heap­ing of cash for these fa­bled five, with the group net­ting a com­bined $2.67 bil­lion — or more than half the to­tal raised by the 30 biotechs that went pub­lic through the usu­al IPO in 2021.

And there’s plen­ty more mon­ey wait­ing in the wings. Since the start of this year alone, an­oth­er 31 SPACs have launched and have yet to find a part­ner. This group has a com­bined $7.8 bil­lion wait­ing in their shell ac­counts and in­cludes SPACs from promi­nent in­vestors such as Fore­site, Per­cep­tive, Ed­uar­do Bra­vo and Vin­od Khosla, the lat­ter of whom launched three.

The blank-check com­pa­nies can take up to two years to find a part­ner, and some an­a­lysts have sig­naled an on­com­ing glut giv­en the sheer amount of SPACs go­ing pub­lic over the last sev­er­al months. Ac­cord­ing to fig­ures from SPACIn­sid­er, there have been 308 SPACs in 2021 al­ready, sur­pass­ing the amount from the last two years, when 2020 saw 248 and 2019 had 57.

For Tan­go, though, that means they can con­tin­ue push­ing their CRISPR-based ap­proach to find­ing new tar­get­ed can­cer drugs. The biotech takes ad­van­tage of CRISPR as a re­search tool, us­ing it to dis­cov­er gene pair tar­gets that cre­ate unique vul­ner­a­bil­i­ties in can­cer cells. It’s sim­i­lar to the un­der­ly­ing the­o­ry be­hind PARP in­hibitors — drugs that go af­ter a pro­tein in pa­tients with a mu­ta­tion on one of the pro­teins used to re­pair DNA.

When us­ing CRISPR to knock out genes, Tan­go re­searchers look for those that when knocked out lead to cell death in a con­cept known as syn­thet­ic lethal­i­ty. These genes then serve as po­ten­tial tar­gets. Though this process had been the­o­rized for years, it wasn’t un­til CRISPR came along in the last decade that it be­came pos­si­ble to do with pre­ci­sion, We­ber said.

The biotech has three pro­grams it in­tends to ad­vance with Wednes­day’s funds, look­ing to file INDs in each of the next three years. First up is TNG908, an MTA-co­op­er­a­tive PRMT5 in­hibitor, ex­pect­ed in the fourth quar­ter of 2021. We­ber said the mon­ey will help gen­er­ate proof-of-con­cept da­ta for the can­di­date in dif­fer­ent tu­mor types.

There’s al­so a USP1 in­hibitor ex­pect­ed in 2022 and an undis­closed tar­get ex­pect­ed in 2023, both of which are ex­pect­ed to hit the clin­ic thanks to the run­way from these funds. The for­mer is look­ing at the treat­ment of BR­CA1-mu­tant breast, ovar­i­an and prostate can­cer, while the lat­ter is go­ing af­ter STK11-mu­tant lung can­cer.

With the tran­si­tion to be­com­ing a pub­lic com­pa­ny now un­der­way, We­ber said the next steps are to keep plug­ging away at their re­search. She’s promis­ing much more dis­cov­ery work com­ing up be­hind the three lead pro­grams.

“We are dis­cov­er­ing three to four [new] tar­gets a year, so we hope to in the fu­ture con­tin­ue to be ad­vanc­ing an IND for a new mol­e­cule, a new tar­get, every 12 to 18 months for the fore­see­able fu­ture,” We­ber said.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

What lured Hal Bar­ron away?; Top FDA minds on ac­cel­er­at­ed ap­proval re­forms; ‘Dead wrong’ Aduhelm ad blitz; 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.

Nothing can really compete with Hal Barron’s departure from GlaxoSmithKline as the news of the week, but we do have plenty of original reporting and analysis from the Endpoints team in this edition. Enjoy and have a nice weekend.

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Mer­ck wins le­gal bat­tle over in­sur­ance cov­er­age af­ter ran­somware at­tack

Merck has emerged victorious from a years-long legal battle with insurers over the coverage of more than a billion dollars in losses from the malware NotPetya, with a New Jersey Superior Court judge concluding that the responsibility is on insurers to clarify their policies around cyber attacks.

The pharma giant was one of several victims of a global cyber attack back in 2017 that also hit Danish shipping company Maersk, American food company Mondelēz, French construction giant Saint-Gobain and even the systems monitoring the Chernobyl nuclear power stations, Bloomberg reported back in 2019.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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