The sand­box: Park­er In­sti­tute throws its re­search mus­cle be­hind gene ther­a­py tech for de­stroy­ing can­cer cells

John Bea­dle

John Bea­dle and the big re­search team at PsiOxus have thought a lot about in­fil­trat­ing the ranks of can­cer cells, to go in­side cells to cause their self-de­struc­tion with one of the in­dus­try’s lead­ing “un­armed” on­colytc virus pro­grams. But they’re al­so go­ing one big step fur­ther, us­ing their gene ther­a­py tech to pen­e­trate these cells to de­liv­er weapons for their mass de­struc­tion. And they’re lin­ing up some pow­er­house al­lies at the Park­er In­sti­tute for Can­cer Im­munother­a­py to speed the work.

What’s the big idea?

PsiOxus — with 95 most­ly re­search staffers in Ox­ford and Philadel­phia — gained con­sid­er­able at­ten­tion for its sys­temic ap­proach to de­liv­er­ing on­colyt­ic virus­es, in­fect­ing cells that would then burst, at­tract­ing T cells in­to the tu­mor. But there are al­so scores of on­colyt­ic virus­es in the pipeline. In this case they’re work­ing a re­verse strat­e­gy to CAR-T. In­stead of mod­i­fy­ing the T cell to go af­ter can­cer cells, they’re mod­i­fy­ing the can­cer cells to get them to en­gage with T cells — en­gi­neer­ing the can­cer cell to ex­press T cell en­gag­ing lig­ands.

The ques­tion has been what genes should be added to do the best job. And they be­lieve the IV ap­proach — steer­ing clear of in­tra­tu­moral in­jec­tions — should help sim­pli­fy things con­sid­er­ably, up­ping their chances of suc­cess in hit­ting the tar­get.

PsiOxus al­ready gained the sup­port of Bris­tol-My­ers Squibb, which part­nered on the biotech’s NG-348 in a $915 mil­lion deal in late 2016. That drug en­codes two im­munomod­u­la­to­ry MiTe pro­teins in its genome: a hu­man CD80 and an an­ti­body frag­ment spe­cif­ic for the T-cell re­cep­tor CD3 pro­tein, both de­signed to muster T cells to at­tack spe­cif­ic can­cer cells on­ly.

Saman­tha Buck­trout

“They’re such a great group,” says Park­er In­sti­tute Di­rec­tor of Re­search Saman­tha Buck­trout about PsiOxus. “When we go to have dis­cus­sions, it’s a ‘no-idea-is-stu­pid’ zone, but al­so an ego-free zone. They’ve done a lot of rig­or­ous work to move their pipeline for­ward, both pre-clin­i­cal and in the clin­ic, and aren’t afraid to take risks. We see a lot of blue sky in terms of where we can go with them, sci­en­tif­i­cal­ly.”

Those blue skies are what spurred tech mogul Sean Park­er to set up his epony­mous in­sti­tute, or­ga­niz­ing a net­work of more than 300 promi­nent sci­en­tists with fi­nan­cial sup­port and cre­at­ing net­works of ex­perts to as­sist the com­pa­nies they work with to dig deep­er and go be­yond the fron­tiers of com­mer­cial I/O. But they’re al­so goal ori­ent­ed, pur­su­ing what PI­CI chief Jeff Blue­stone calls a “sand­box” strat­e­gy: a con­tained, or­ga­nized ap­proach to their work dri­ven by a set of clear ob­jec­tives.

Ex­tra fund­ing is al­ways good, says Bea­dle, but it’s the peo­ple Park­er brings to the ta­ble that make the big dif­fer­ence.

“The key is their net­work of in­sti­tu­tions and aca­d­e­mics,” notes the CEO, who ex­pects to even­tu­al­ly put to­geth­er an­oth­er round for the biotech be­fore even­tu­al­ly set­ting their sights on an IPO.

The plan at PsiOxus is to move two pro­grams in­to the clin­ic, with an IND com­ing in Q1 of next year. The first is a CD40 ag­o­nist, and the sec­ond will in­clude a pack­age of 4 dif­fer­ent genes cov­er­ing a bis­pe­cif­ic with chemokines to at­tract T cells and an­oth­er to ex­press in­ter­fer­on al­pha to ac­ti­vate den­drit­ic cells.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

No­var­tis is ax­ing 150 ear­ly dis­cov­ery jobs as CNI­BR shifts fo­cus to the de­vel­op­ment side of R&D

Novartis is axing some 150 early discover jobs in Shanghai as it swells its staff on the drug development side of the equation in China. And the company is concurrently beefing up its investment in China’s fast-growing biotech sector with a plan to add to its investments in local VCs.

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No­var­tis is eye­ing a multi­bil­lion-dol­lar Med­Co buy­out as Jer­sey biotech nears NDA — re­ports

To get from Novartis’ US headquarters to the Medicines Company, you make a left out of a square concrete building on NJ-Route 10, follow it past the sun orange veranda of Jersey’s Hot Bagels and the inexplicable green Vermont cabin that houses the Whippany Railway Museum until you turn right and immediately arrive at a rectangular glass building. It should take you about 12 minutes.

Reports are out that Novartis may be making that trip. Amid a torrent of Phase III data burnishing MedCo’s chances at a blockbuster cholesterol drug,  Bloomberg News is reporting that Novartis is looking to acquire the Jersey-based biotech.

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UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

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Badrul Chowdhury. FDA via Flickr

As­traZeneca los­es an­oth­er ex­ec­u­tive to biotech, as Badrul Chowd­hury moves to Savara

Another executive is migrating from the echelons of Big Pharma to the corridors of small biotech.

In April 2018, Badrul Chowdhury took his more than two decades of experience at the FDA to AstraZeneca, where he took on the role of senior vice president and chief physician-scientist for respiratory, inflammation and autoimmunity late-stage development in biopharmaceuticals R&D.

After about a year and a half in this role, Chowdhury is moving to a small Texas biotech called Savara, where he will serve as chief medical officer.

Yiannis Kiachopoulos and Artur Saudabayev, co-founders of Causaly

Lon­don AI up­start, which counts No­var­tis as a cus­tomer, can teach your com­put­er to read

When Amazon developed a machine-learning tool to make its recruitment process more efficient — the man-made system absorbed the gender-bias of its human makers, and the project was aborted. In the field of biopharmaceuticals, the way researchers train their machine learning algorithms can skew the outcome of predictions. But before those predictions can be made, the engine must learn to read to make sense of explosive volume of knowledge out there.

Burt Adelman. Novo Ventures

Here's a $25M seed fund aimed at back­ing some brash new drug ideas out of the Broad

As a former academic and a seasoned drug developer, Burt Adelman knew when he was recruited as a senior advisor to Novo Ventures in 2017 that one of his key priorities needs to be introducing the fund to the network he was so deeply embedded in.

“I was thinking long and hard on how can I, as a Boston insider, help Novo really get inside the ecosystem of Boston biotech?” he recalled in an interview with Endpoints News.

Welling­ton lines up a $393M bankroll for its next round of pri­vate biotech bets — and they’re like­ly think­ing big

Wellington Management made some uncustomary waves at the beginning of the year when it threw its considerable weight against Bristol-Myers Squibb’s $74 billion Celgene buyout. But after Bristol-Myers’ biggest investor conceded that game to the influential proxy firms involved, they’re now going to end the year by rolling out a big new investment fund for a new stable of fledgling biotechs on the private side of the industry.

As uter­ine race with Ab­b­Vie heats up, My­ovant eyes FDA ap­proval with tri­al re­sults from prostate can­cer

Myovant has long had a secret weapon in its uterine rivalry with AbbVie: Men.

While the small Swiss biotech has jockeyed with the Illinois-based giant for a foothold in the endometriosis and uterine fibroid therapy market, the company has been developing the same lead compound, relugolix, for use in one of the most common cancers for the uterus-less: prostate cancer. Today, Myovant is out with positive topline results from its big Phase III trial on the gonadotropin-releasing hormone (GnRH) antagonist. They say they’ve reached every primary and secondary endpoint with p values less than .0001.