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.”

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

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.

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III Voyage trial before they give a judgment.

Late last year Novartis abandoned a cardio drug from Ionis’ spinoff Akcea just after the pharma giant snapped up inclisiran, going the RNAi way in guarding against heart disease in the $9.7 billion Medco buyout.

Now the pharma goliath — which is headed down the PCSK9 road with a drug it believes can be used in a mass population — can get a clearer picture of just what they gave up.

Akcea $AKCA and the mother company $IONS put out a statement early Wednesday saying that their Phase II study of AKCEA-APOCIII-LR delivered solid efficacy data, with the high dose clearly outperforming placebo in significantly reducing triglycerides as a means to cutting the risk of cardiovascular disease. In addition, investigators concluded that the drug slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting “good” HDL levels.

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.