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March 2019

Book review: ‘La Photographe’

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As a student at Paris’ SciencesPo, I would occastionally bemoan the seeming absence of, or my seclusion from, literary and artistic genius in the City of Lights in the 21st century, relative to its illustrious past. It is all the more exciting to witness the literary coming-of-age of a young French writer, a personal acquaintance who at 23 was awarded France’s ‘young writer’s prize’ and who at 25 just published her first novel with Gallimard, the leading French publishing house once described as having the best backlog in the world.

Cover of “La Photographe” by Diane Chateau-Alaberdina. Source: Gallimard

Diane Chateau-Alaberdina’s first published novel is reflective of the young author’s uncommonly profound perceptiveness, paired with a wealth of insight into the plight of womanhood and the perennial pathological tendency for people to exert control over objects of desire. 

If fogginess – as a feature of the environment but foremost as an apt description of a contemporary malaise and that particular melancholy afflicting the Russian diaspora – emerges as a recurrent theme throughout the book, it is pierced by the author’s aptitude at pacing the narrative’s progression with sharp yet elegant introspective and descriptive morsels. Throughout, this is a sophisticated yet unpretentious verbal painting.  

The fog-of-war enveloping the trajectories of several Russian families, beginning with the hazy past of the protagonist’s father as a warzone photographer, over the mystery shrouding the ever-present antagonist ‘Agafonova’ and the unexplained wealth of “the photographer’s” subject and her husband, invites us to indulge in the author’s carefully crafted, yet seemingly effortless, exploration of the ‘inner worlds’ which eclipse comparably mundane surroundings and careers.  

The theme of photography as explored here is reminiscent of an act of rebellion against the fleeting nature of existence; of an act of vanity whose short-lived fascination fails to fill a void whose presence is felt throughout the book. Where the photographer’s flash, her voyeur-like examination of the subject’s features and physical deterioration ostensibly lead to a rapprochement, a sisterhood of sorts, they fail to prevent the most tragic of outcomes.  

La Photographe stands out as an unusually honest examination of the failings of inter-personal relationships and of some of modern society’s dirty secrets, such as the abuse of anxiolytic prescription drugs as a treacherous escape from our troubles. The failings and temptations of the book’s characters are internalized, contained within discreet family structures and tightly knit spheres of influence. Quiet lives devoid of ecstasy are contrasted by the protagonist’s mind games and a cruel ‘long con’ which finds unexpected closure. If a dreamy fogginess serves as a metaphor for our complex yet often uprooted and unfulfilling contemporary lives, it is not the only theme that emerges from Diane’s writings. Escape – escape from the motherland, escape from a mundane existence, escape from manipulative others permeates the book. Eventually, all of these escapes are semi-failures: for the protagonist’s brother, escaping an unhealthy obsession is rendered futile by means of willful and skilled manipulation; for all main characters, emigration from Russia to the West seems contrasted by unquenchable nostalgia.  

La Photographe is brutally candid in exploring the frailty of life; suggestive of a deep sadness rooted in separation, longing, denial and decline; subtle at providing anything resembling judgment or catharsis. The simplistic disapproval of a lone, anonymous exhibition-goer falls short of providing the speech required to counter the silent suffering present throughout this novel. 

All in all, La Photographe is a remarkable debut; sensible, observant, reflective, subtle yet forceful, potentially shocking to the uninitiated. A thought-provoking stepping stone towards, hopefully, an enduring string of intelligent writing capable of lifting the fog-of-war of our contemporary existence bit by bit. 

Intercept’s NASH fibrosis breakthrough and perceptions around commercial viability

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Intercept Pharmaceuticals, which develops & commercializes obeticholid acid (‘OCA’) in several indications, has reported positive PhIII data from a study in NASH patients with fibrosis. As I wrote on SeekingAlpha last month, liver fibrosis is recognized both by FDA and independent researchers as the strongest predictor of adverse clinical outcomes in NASH patients. It follows that OCA’s ability to demonstrate a clear fibrosis benefit that appears to be dose-dependent in a large PhIII trial poises the molecule to become the first FDA-approved treatment for NASH fibrosis.
With some 20m patients estimated to suffer from NASH in the United States, OCA would only need to capture a diminutive portion of the overall market opportunity over time to 1) lead Intercept to profitability 2) justify a significant multiple of the company’s current $3.15bn Mcap.

Above: OCA’s PhIII data showing dose-dependent fibrosis improvements at month 18. Source: Intercept

OCA is currently marketed as OCALIVA in a rare condition called primary biliary cholangitis (‘PBC’), where it retails for roughly $70k/year.
Together with the frequency of dose-dependent pruritis in the NASH fibrosis study, this has raised questions around OCA’s commercial viability in NASH. A few things to consider:
– If OCA is approved in NASH fibrosis, lowering its unit price across PBC & NASH with a view on maximizing NASH revenues is trivial and makes sense economically (a multi-million potential market in NASH far outweighs a few thousand patients in PBC)
– Intercept would first launch OCA in NASH through the same physician network (e.g. hepatologists) it has already established via OCALIVA’s launch in PBC. The company would likely target sub-groups of patients who at high risk for progression to liver Cirrhosis.
– Titration will be used to minimize pruritis as an adverse effect leading to drug discontinuation. With only 5% of patients experiencing severe pruritis, there remains a very large patient population who might benefit from OCA.
Additional considerations such as OCA’s tendency to raise lipid levels in blood & other metabolic implications will be taken into account by treating physicians but all in all do not reduce commercial opportunity to the point of making a NASH launch trivial for Intercept.
Naturally, an established global player with a strong presence in metabolic & cardiovascular disease could speed up OCA’s sales ramp in NASH dramatically, which leads me to think that an acquisition of Intercept by Big Pharma or the likes of Gilead is near-inevitable – barring any major setbacks on the regulatory front.
On social media, the discussion around OCA’s commercial potential is likely to simmer on, with a negative spin being almost inevitable as proponents of competing approaches, notably of Madrigal and Viking’s thyroid hormone receptor approach aimed at lowering liver fat, tout the prospect of better drugs following into OCA’s footsteps. My take is that these are complimentary approaches and the very early stage nature of Viking’s compound in particular should not lead to investor exuberance at present.

A more serious question raised on social media is likely adoption of OCA, regardless of competing efforts, purely on the basis of physicians buy-in. Several analysts have conducted limited physician polling, and I would caution against drawing premature conclusions from extremely small samples such as the 2 physicians being quoted in this tweet:

All in all, I expect institutional investors to increase their Intercept positions while traders & retail investors quibble about what looks to me like marginally relevant considerations with regards to OCA’s peak sales potential in the light of a first-to-market advantage. NASH fibrosis is now literally Intercept’s for the taking and the only real question is whether and how quickly OCA will become a blockbuster in this indication.
When it does, investors may regret not buying into ICPT when it was still moderately priced.