Snippet roundup: A Pacific use for Imfinzi but Crispr gets the Zinc finger

Welcome to your weekly roundup of EP Vantage’s snippets – short takes on smaller news items.

This week, February 19-23, 2018, we had thoughts on the following: Apellis sees path ahead for APL-2 despite side-effect doubts; Gilead gives Crispr the Zinc finger; Darzalex doubts dashed; another Hanmi-back for Korea’s prolific deal maker; the eyes have it for Google’s heart test; Hikma C-suite overhaul warms up the market; Astra makes waves in first-line lung cancer.

These snippets were previously published daily via twitter.

Apellis sees path ahead for APL-2 despite side-effect doubts

February 23, 2018

Apellis Pharmaceuticals faces a delicate balancing act with the geographic atrophy candidate APL-2 in its upcoming phase III trials. 18-month phase II data have confirmed the benefit seen at one year with a monthly injection of APL-2 – but the number of patients developing a related condition, wet age-related macular degeneration, increased. Wet AMD was not such a problem with APL-2 dosed every other month, but this regimen had a less pronounced effect on the primary endpoint, change in lesion size at 12 months versus sham therapy. And neither APL-2 regimen tested in the phase II Filly trial led to an improvement in visual acuity, at either 12 or 18 months. Apellis plans to start two 600-patient phase III trials in the second half that will have the same primary outcome; however, the company has not said which dosing regimen(s) the studies will evaluate. Geographic atrophy is an advanced form of dry AMD that causes irreversible vision loss and for which no specific therapies currently exist. Although there are treatments available for wet AMD, this also leads to blindness – and patients might not want to take the risk of swapping one for the other.

Gilead gives Crispr the Zinc finger

February 22, 2018

Zinc finger nucleases, a genome-editing tool that had been around for a long time but never grabbed the headlines as much as Crispr Cas 9, just got a major endorsement, with Gilead handing across $150m to Sangamo to access the technology. This signals another stage in the rehabilitation of Sangamo, whose stock climbed 19% this morning, hitting levels not seen for over 15 years. The deal followed last month’s Zinc finger tie-up with Pfizer in ALS, which itself built on a 2017 transaction under which Pfizer licensed Sangamo’s haemophilia A gene therapy SB-525. The Gilead tie-up has a cell therapy focus, following Gilead’s $11.9bn acquisition of the CAR-T company Kite Pharma last year, and seeks specifically to develop allogeneic cell therapy products. Most of the big CAR-T players have struck deals to access genome-editing technologies – mostly Crispr Cas 9. Gilead’s focus suggests that there is utility in the previously unfashionable Zinc finger approach after all, as well as perhaps being a tacit admission of the intellectual property minefield surrounding Crispr Cas 9.

Darzalex doubts dashed 

February 22, 2018

Confidence in Genmab’s multiple myeloma therapy Darzalex has been restored – for now – with the group’s 2018 guidance. Genmab expects sales of the product to reach $2-3bn this year, above current consensus, and the relief among investors was palpable – the Danish group’s shares jumped as much as 16% this morning. Darzalex became a blockbuster in 2017, but fourth-quarter revenues of $371m, reported by Genmab’s partner Johnson & Johnson last month, fell short of expectations. And disappointing January sales, tracked by Symphony Health, did not help allay investor jitters. ABG Sundal Collier analyst Andrew Carlsen had feared the worst, saying in the run-up to Genmab’s results that there was a risk that 2018 Darzalex guidance could be as low as $1.8-2bn. Now Darzalex could hit a $10bn peak in 2030, he believes – but much is riding on the upcoming Maia readout in first-line multiple myeloma, in combination with Celgene’s Revlimid. A result here would give Genmab and J&J access to the lucrative US first-line market; results are due mid-year.

Another Hanmi-back for Korea’s prolific deal maker

February 21, 2018

Hanmi’s streak of licensing deals could be unravelling further. News that Lilly discontinued phase II trials of the BTK inhibitor poseltinib (LY3337641) on efficacy concerns looks ominous for yet another R&D pact – Hanmi’s success at attracting Western partners from 2015 catapulted the South Korea company onto the global stage and made it a domestic success story. Lilly has not said anything about the decision over poseltinib, and clinical trials registries do not appear to show any early termination of the studies, though presumably the fact that Hanmi has moved to update stock market regulators spells the end of research in rheumatoid arthritis. Hanmi insists that further work with the asset is under discussion, but investor nervousness is understandable given the substantial re-working of a Sanofi diabetes deal last year, under which the French drug maker abandoned one asset, cut milestone and development funding and clawed back almost half of its up-front fee. And late in 2016 a Boehringer Ingelheim deal was declared dead in the water. Drug development is always a risky business but investors are probably wondering whether Hanmi’s substantial share price recovery last year was justified – its stock more than doubled in value over 2017, but has dropped back 20% so far this year. 

The eyes have it for Google’s heart test

February 20, 2018

The eyes are the windows to the soul – but not for Google. Yesterday Google’s Verily division unveiled data showing that one of its deep learning models could identify a patient’s risk of heart attack by examining retinal images. Using data from over 280,000 patients the tech group said it had managed to predict correctly which patients were at risk of heart attack or a major cardiovascular event 72% of the time. While this result did not outperform blood tests, Verily’s approach does show the potential of deep learning – a branch of artificial intelligence. The study evolved from a previous successful 2016 trial in diabetic retinopathy. The big caveat, however, is that despite containing more than a quarter of a million images the dataset was relatively small for deep learning. The issue of standardisation of data also remains one of the biggest challenges in this new world. As such, the true potential of this particular field could be years away, but the advances Google is making in diagnostics and machine-based learning should rightly make both pharma and medtech companies sit up and take notice. Those looking to reduce healthcare costs through the speed of processing and increasing accuracy machine learning offers will almost certainly be paying attention.

Hikma C-suite overhaul warms up the market

February 20, 2018

In times of crisis an executive overhaul rarely has an immediate effect, but for the struggling UK-listed generics company Hikma it seems to have done the trick. Separation of the chairman and chief executive roles, and replacement of Said Darwazah in the latter function with Sigurdur Olafsson, sent the group up 9% this morning. The reason for cheer might have less to do with hopes of an imminent recovery and more with prospects of business development: Mr Olafsson is a director of the US-listed biosimilars player Pfenex and, more importantly, used to head up Teva’s generics business. Increased ties here will do Hikma no harm at all, and a radical move might be just what the doctor ordered: the company should be making the most of being one of a handful of players that have developed US generic versions of Glaxosmithkline’s blockbuster Advair, but instead has become embroiled in a dispute with the FDA. Resolution of this, and an upcoming US regulatory verdict on Mylan’s reply to a complete response letter, are the next key events to watch. In the meantime Hikma stock remains 60% off its mid-2016 high.

Astra makes waves in first-line lung cancer

February 19, 2018

US approval for Astrazeneca’s Imfinzi in a new first-line lung cancer niche could catapult the product from a checkpoint inhibitor also-ran to a major player. And of its rivals, Bristol-Myers Squibb should be particularly worried. Imfinzi’s approval in stage III, non-metastatic NSCLC puts it ahead of Merck & Co’s Keytruda and Roche’s Tecentriq in the treatment cascade, with the latter two drugs set to fight over the stage IV market. Meanwhile, Bristol’s bid to break into the first-line space stumbled when its Opdivo/Yervoy combo could only get a result in subjects with a high tumour mutation burden in the Checkmate-227 trial. Any hopes that Imfinzi could steal patients from Keytruda and Tecentriq by going earlier stage are probably unfounded – at diagnosis most have stage IV disease – unless Astra can push for earlier detection. Still, Imfinzi, which currently accounts for around 2% of the PD-(L)1 market, could see a big boost in sales: Leerink analysts expect peak sales of $3.8bn by 2026, up from $2.3bn previously. With Astra, Merck and Roche looking to carve up the first-line lung segment, Bristol’s dominant position could soon fade – particularly if it cannot get Opdivo out of the second-line segment.

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