Re­searchers use PD-1 check­point drug in pur­suit of a promis­ing cu­ra­tive ap­proach to HIV

The big drug de­vel­op­ers like Gilead and Glax­o­SmithK­line learned years ago how to keep a lid on HIV, but re­searchers re­main chal­lenged by their in­abil­i­ty to root out the la­tent reser­voirs of virus the hide in the cells.

But now in­ves­ti­ga­tors are pur­su­ing a new re­search track that has just demon­strat­ed its po­ten­tial in a can­cer pa­tient in France.

Jean-Philippe Spano

Doc­tors there were treat­ing a lung can­cer pa­tient with HIV with Bris­tol-My­ers Squibb’s Op­di­vo and ob­served a “dras­tic and per­sis­tent de­crease” in the virus hid­den in cells. And there may be a very sim­ple ex­pla­na­tion.


Treat­ing HIV pa­tients with a PD-1 drug ac­ti­vates CD4 T cells, where the virus grav­i­tates to hide. First gen­er­at­ing a re­sponse by ac­ti­vat­ing the virus, they then ex­pose it to an amped up im­mune sys­tem in pa­tients on pow­er­ful an­tivi­rals.

Doc­tors have been treat­ing the 51-year-old pa­tient — first di­ag­nosed with HIV in 1995 — since late last year. Be­fore treat­ment, the HIV was un­de­tectable. But as treat­ment be­gan the virus be­gan to ap­pear and then con­tin­ued to rise for 45 days, at which point the im­mune re­sponse be­gan to wipe out the ex­posed HIV.

“In­creas­ing­ly, re­searchers have been look­ing in­to the use of cer­tain drugs that ap­pear to re-ac­ti­vate the la­tent HIV-in­fect­ed cells,” Pro­fes­sor Jean-Philippe Spano, head of the med­ical on­col­o­gy de­part­ment at Pitie-Salpetriere Hos­pi­tal AP-HP in Paris. “This could have the ef­fect of mak­ing them vis­i­ble to the im­mune sys­tem, which could then at­tack them. Drugs that in­hib­it im­mune check-points such as PD-1 are well known in the can­cer field as be­ing very ef­fi­cient at restor­ing im­mune de­fences by re­mov­ing the brake, en­abling the im­mune cells to spring in­to ac­tion to re­ject the can­cer cells. It was thought, but un­til now not demon­strat­ed, that in­hibitors of im­mune check-points could, in a sim­i­lar way, wake up dor­mant HIV-in­fect­ed cells and al­so the im­mune de­fences against the virus.”

There are some big caveats at­tached to this an­nounce­ment. First, there was an­oth­er HIV pa­tient treat­ed with ni­vo who didn’t re­spond. Sec­ond, they have to com­plete tox test­ing to see if non-can­cer pa­tients are threat­ened by check­point ther­a­py. And they have to de­vel­op bio­mark­ers for per­son­al­ized treat­ment.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

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Left to right, top to bottom: Carl Gordon, Adam Stone, Peter Moglia, David Schenkein, Robert Nelsen, Carol Gallagher; Srinivas Akkaraju, Ray Debbane, Jim Flynn, Peter Kolchinsky, Thilo Schroeder, Brad Bolzon

UP­DAT­ED: The top 100 bio­phar­ma ven­ture in­vestors at the mega­bil­lions deal ta­ble

The VC crowd took a step back last year, but nevertheless maintained a furious pace of new investments in therapeutic tech platforms and biotech startups. And the top 100 players completely dominated the megabillions game.

Just looking at the number of deals done by each of the top 100, OrbiMed came in at the top, with 20, followed by Alexandria (18), Perceptive (16) and the ubiquitous RA Capital at 16. It’s impossible to say exactly how much they invested in total — those numbers are only rarely provided — but it is clear from the numbers assembled by Chris Dokomajilar at DealForma who’s most likely to be found sitting at the table during the go-go days of biotech investing.

Dokomajilar tracked $14.06 billion in biotech venture investing last year, a dip from the frenzied pace of $16.02 billion in 2018 and more than $10 billion higher than he recorded for 2010, as the economy was recovering from a profound economic crisis.

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Rahul Ballal, Imara

As sick­le cell pa­tients find new op­tions, NEA-found­ed Imara pitch­es mid-stage al­ter­na­tive for $86M IPO

November 2019 proved to be a fruitful month for patients with blood disorders known as hemoglobinopathies. Within days, the FDA ushered two drugs for sickle cell disease and another for beta thalassemia to the market — livening up a barren field.

Imara, a relatively young plower, is riding on that enthusiasm as it shoots for an $86.25 million IPO.

Imara emerged from New Enterprise Associates’ orphan drug accelerator Cydan in 2016 as a single-product company. $77.3 million in private financing later IMR-687 remains the sole asset in its pipeline; the difference is the drug is now in Phase II for sickle cell disease, with topline data slated for later this year and two other mid-stage beta thalassemia studies lined up.

UP­DAT­ED: RA joins glob­al syn­di­cate to back a $98M round for CAN­bridge

A Beijing-based rare disease and oncology player has raised $98 million to help fund the expansion of its pipeline as well as a commercial portfolio.

CANbridge put out word Tuesday that the global private equity player General Atlantic joined forces with Chinese CRO Wuxi AppTec to lead the Series D, with both ready to chip in an extra $10 million each under the right conditions. The syndicate includes RA Capital Management, Hudson Bay Capital Management, YuanMing Prudence Fund and Tigermed.

Carol Robinson, Professor Dame Carol Robinson Research Group

UP­DAT­ED: Drug dis­cov­ery in HD: Ox­ford spin­of­f's mass spec­trom­e­try ap­proach scores fresh fund­ing

The technology used to detect explosives at airports — mass spectrometry — is being piloted as an engine for drug discovery.

Mass spectrometry is a tool designed to measure with profound accuracy the mass of a single molecule. Typically, mass spectrometers can be used to identify unknown compounds, to quantify known compounds, and to determine the structure and chemical properties of molecules.

Lars Fruergaard Jørgensen, chief executive officer of Novo Nordisk A/S, (via Getty Images)

The list of the 11 block­busters-to-be in line for a 2020 launch high­light agony and ec­sta­sy of drug R&D

For all the talk about unmet medical need and patients first and so on, the key criteria investors watch for any new drug in the pipelines is peak sales projection. Are you going to hit the blockbuster mark, at $1 billion-plus, or are you going to be an also-ran in the sales department?

Of course, analysts’ peak sales projections by themselves are of limited value in many cases. When the PCSK9 drugs started arriving 5 years ago, Repatha was billed as a $2.5 billion peak earner. They’re nowhere near that, with new competition threatening current levels. And if Biogen’s controversial Alzheimer’s drug aducanumab (submission planned but not on the list) is approved, per chance, will payers cover it?

Maybe not. And then those $10 billion in peak sales assumptions would go straight down the drain.

But, analysts are analysts, and peak sales projections have to be factored in when assessing the top experimental drugs up for a launch in the year ahead.

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UP­DAT­ED: Chi­na ap­proves flu drug be­ing tout­ed as a po­ten­tial coro­n­avirus treat­ment amid a rush of clin­i­cal stud­ies

One of the three drugs that China’s Ministry of Science and Technology has tapped as potential COVID-19 treatments to watch has notched its first Chinese OK — for the flu.

While there’s no proof yet that fapilavir, or favipiravir, is the cure that patients and physicians are yearning for, it stands out for a unique constellation of qualities. It’s been commercially available in Japan for several years (unlike Gilead’s experimental remdesivir) yet it’s new to China (unlike the malaria drug chloroquine phosphate). Perhaps more importantly, a domestic biotech — Zhejiang Hisun Pharma — owns the rights to manufacture and market the drug, preempting any concerns about patents.

FDA goes on high alert as coro­n­avirus rais­es threat to drug man­u­fac­tur­ing and clin­i­cal tri­als grind to a halt

The FDA isn’t quite sure just what the coronavirus outbreak in China will mean for the US pharma industry, but it has the potential to trigger a host of troublesome issues around the supply chain the country is directly plugged into.

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