Steve Worland. eFFECTOR

Eye­ing the 'trans­latome,' Pfiz­er ties an­oth­er knot with biotech part­ner for pre­clin­i­cal, next-gen tar­get­ed ther­a­pies

Af­ter close­ly fol­low­ing eF­FEC­TOR Ther­a­peu­tics’ work on next-gen tar­get­ed can­cer ther­a­pies in the past two years, chip­ping in its own ven­ture dol­lars and ink­ing an I/O com­bo col­lab­o­ra­tion with its PD-L1, Pfiz­er is bet­ting on a sec­ond drug can­di­date from the biotech part­ner.

The pre­clin­i­cal deal starts rel­a­tive­ly small — $15 mil­lion up­front — but Pfiz­er has com­mit­ted to $492 mil­lion in R&D fund­ing and mile­stones, as well as roy­al­ties and an op­tion to co-pro­mote in the US.

With Pfiz­er shoul­der­ing some re­spon­si­bil­i­ty, eF­FEC­TOR can now de­vote more of its re­sources and time to the clin­i­cal de­vel­op­ment of its lead pro­gram, CEO Steve Wor­land told End­points News.

Jeff Set­tle­man

The pact cen­ters around eu­kary­ot­ic ini­ti­a­tion fac­tor 4E, or eIF4E. Like MNK — the tar­get of eF­FEC­TOR’s lead ther­a­py tomivosert­ib (for­mer­ly eFT508) — eIF4E is part of the PI3k/AKT/mTOR and RAS onco­genic path­ways. Un­like tomivosert­ib, though, eIF4E in­hibitors are de­signed to act with­in the tu­mor rather than im­muno­sup­pres­sive fac­tors in T cells.

Sit­ting near the end of the whole process of mak­ing pro­teins — af­ter DNA has been tran­scribed, with the mR­NA ready to be trans­lat­ed by ri­bo­somes — eIF4E is in­stru­men­tal in ac­tu­al­ly kick­ing off the process of mak­ing pro­teins. Can­cer cells re­ly on this mech­a­nism to cre­ate what they need to pro­lif­er­ate; in fact, the trans­la­tion com­po­nent gets tur­bocharged, Wor­land said.

Hit­ting the end of that whole process al­so means tar­get­ing where mul­ti­ple mu­tat­ed genes and re­cep­tors con­verge.

“So if you’re down­stream, you may col­lect a set of dif­fer­ent mu­ta­tions that all ac­ti­vate your tar­get; any one of those mu­ta­tions can con­fer sen­si­tiv­i­ty,” he said.

By fo­cus­ing on the “trans­latome,” Wor­land added, eF­FEC­TOR al­so hopes to cir­cum­vent the feed­back loops in which tu­mor cells sense that one path­way has been blocked and quick­ly switch to an al­ter­na­tive.

“That was the ori­gin of the com­pa­ny, re­al­ly, look­ing at tar­get­ed ther­a­pies and high re­sponse rates, but un­for­tu­nate­ly some­times short dura­bil­i­ty of re­sponse, and think­ing: how can we think about the path­ways and find the points where you aren’t nec­es­sar­i­ly sus­cep­ti­ble to those re­sis­tance mech­a­nisms?” he said. “So we con­scious­ly chose to go down­stream of the onco­genes (and tar­get) the ef­fec­tor com­plex.”

The dis­cov­ery pro­gram is now in a rel­a­tive­ly ma­ture stage, ac­cord­ing to Wor­land, hav­ing de­vot­ed much ef­fort in mov­ing from a nat­ur­al lig­and that’s “lightyears from drug­like space” to an oral­ly avail­able ther­a­py that fits in­to the bind­ing site.

Jeff Set­tle­man, Pfiz­er’s chief sci­en­tif­ic of­fi­cer in on­col­o­gy, high­light­ed its promise for pa­tients with var­i­ous treat­ment-re­frac­to­ry can­cers.

The two part­ners are con­tin­u­ing to test eF­FEC­TOR’s MNK1/2 in­hibitor tomivosert­ib with Pfiz­er/Mer­ck KGaA’s Baven­cio. Pre­lim­i­nary da­ta from a Phase I/II study pre­sent­ed at AS­CO sug­gest­ed that “the com­bi­na­tion of T and avelum­ab has an ac­cept­able safe­ty pro­file with ro­bust tar­get en­gage­ment and demon­strat­ed ini­tial signs of ac­tiv­i­ty.”

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Por­tion of Neil Wood­ford’s re­main­ing in­vest­ments, in­clud­ing Nanopore, sold off for $284 mil­lion

It’s been precisely one year and one day since Neil Woodford froze his once-vaunted fund, and while a global pandemic has recently shielded him from the torrent of headlines, the fallout continues.

Today, the California-based patent licensing firm Acacia Research acquired the fund’s shares for 19 healthcare and biotech companies for $284 million.  Those companies include shares for public and private companies and count some of Woodford’s most prominent bio-bets, such as Theravance Biopharma, Oxford Nanopore and Mereo Biopharma, according to Sky News, which first reported the sale. It won’t include shares for BenevelontAI, the machine learning biotech once valued at $2 billion.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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