When Adri­an Raw­cliffe of­fi­cial­ly steps in­to the CEO role at Adap­ti­m­mune in a few days, he will have a new part­ner­ship to ex­e­cute in one of his first ef­forts to shore up some en­thu­si­asm for its T cell ther­a­py pro­grams.

Adri­an Raw­cliffe

In a $312 mil­lion pact, the US-UK hy­brid biotech has en­list­ed Noile-Im­mune for a next-gen­er­a­tion project that will boost Adap­ti­m­mune’s SPEAR T cells with the Japan­ese com­pa­ny’s PRIME plat­form. In ad­di­tion to the re­cep­tors en­gi­neered in­to the T cells, the re­sult­ing prod­uct would be armed with the cy­tokines IL-7 and CCL19.

Noile-Im­mune has been ap­ply­ing their tech­nol­o­gy — in­vent­ed by Ko­ji Tama­da of Ya­m­aguchi Uni­ver­si­ty — to CAR-T cells, pre­vi­ous­ly ink­ing a co-de­vel­op­ment deal with Take­da.

Not on­ly does PRIME make the en­gi­neered cells more po­tent, it may al­so en­hance the abil­i­ty of the pa­tient’s na­tive T cells to fight sol­id tu­mors, ac­cord­ing to Karen Miller, Adap­ti­m­mune’s SVP of pipeline re­search.

Karen Miller

“We re­cent­ly start­ed our Phase 2 tri­al in sar­co­ma called SPEAR­HEAD-1 as well as the SUR­PASS tri­al, our first next-gen­er­a­tion prod­uct clin­i­cal tri­al. We will con­tin­ue to de­vel­op en­hanced prod­ucts with the aim of in­creas­ing the ef­fi­ca­cy and dura­bil­i­ty of an­ti-tu­mor re­spons­es,” she added in a state­ment.

It’s crunch time for Adap­ti­m­mune. Once a dar­ling in the I/O crowd with a bud­ding TCR tech, its sup­port on Wall Street has been wan­ing since its $191 mil­lion pub­lic de­but in 2015, which in turn fol­lowed a high pro­file $350 mil­lion col­lab­o­ra­tion with Glax­o­SmithK­line. The stock opened at $1.47 to­day, a pre­cip­i­tous fall from last fall’s peak of $13.9. As founder James No­ble pass­es the reins to CFO Raw­cliffe — a GSK vet — the theme now is to make things hap­pen.

Adap­ti­m­mune will now work with Noile-Im­mune on pre­clin­i­cal work around a num­ber of tar­gets, with a goal to en­ter the clin­ic by 2021. That will all hap­pen un­der a new CMO and R&D pres­i­dent af­ter Rafael Ama­do hit the ex­it ear­li­er this month.

At last count the com­pa­ny had about $35 mil­lion in cash on hand and $133 mil­lion in liq­uid­i­ty, giv­ing it a run­way that ex­tends in­to the third quar­ter of next year.

So­cial im­age cred­it: Navy Yard

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.

More than 3 years after Merck stepped up and paid $1 billion in cold, hard cash to gain the US commercial rights to Bayer’s high-risk heart drug vericiguat in a broad-ranging cardio alliance, the partners say their Phase III study has come through with promising data and a date with regulators.
We don’t have the data, and won’t until they put it out at an upcoming scientific session, but Merck touted the results, saying that their big Phase III VICTORIA study hit the primary endpoint  — with vericiguat combined with available therapies reducing “the risk of the composite endpoint of heart failure hospitalization or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) compared to placebo when given in combination with available heart failure therapies.”
Depending on the hard data, and how it breaks out with the combinations used, this drug could pose a threat to Novartis’ blockbuster drug Entresto, currently at $1.6 billion while analysts expect peak sales to hit $4 billion.
The drug is a soluble guanylate cyclase (sGC) stimulator, which Bayer and Merck have had high hopes for. Evidently, so did cardiologists. Cowen’s last analysis set potential sales at $400 million in 2024, but that number could go up significantly now.
Cowen’s Steve Scala noted this morning:
Vericiguat could be a lucrative product for Merck, and one with potentially under-appreciated value. At Cowen’s Therapeutics Conference in September 2019, 80% of specialists anticipated a positive result from VICTORIA whereas only 51% of investors shared this optimism.
Investigators recruited more than 5,000 patients at more than 600 centers in 42 countries for this study — one of the most expensive propositions in R&D. Millions of people in the US suffer from heart failure with reduced ejection fraction when the failing heart fails to contract properly to eject blood into the system. Bayer holds ex-US rights to the drug and also stands to earn cash from the $1.1 billion in milestones Merck agreed on for their collaboration.
Remarkably, the drug was pushed into Phase III despite failing the mid-stage trial — though investigators flagged a success at the high dose of 10 mg. In VICTORIA, researchers started patients at 2.5 mg and then titrated up to 5 and then 10 mg.

Turns out Dicerna wasn’t done with deals yet after locking in $200 million upfront from Roche for a hepatitis B cocktail two weeks ago.

Novo Nordisk has signed on as the latest partner to its GalXC RNAi platform, handing over $175 million in cash to claim any and all targets of interest in liver-related cardio-metabolic diseases that are not already reserved in previous pacts. The Danish drugmaker — which has signaled its interest to expand considerably beyond its core diabetes franchise into areas like NASH — is also purchasing $50 million worth of Dicerna’s equity at a 25% premium of $21.93 per share. More research payments and milestones extending to the billions are on the line.

→ Gene therapy maker Orchard Therapeutics has been granted an accelerated assessment for OTL-200 by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The gene therapy — in development in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy — being used towards the treatment of metachromatic leukodystrophy.

→ Pharmaceutical Product Development has announced that its parent company, PPD, Inc has submitted a draft to the SEC relating to the proposal of an IPO of the parent company’s common stock. Number of shares and price range have not yet been determined.

In the story lawmakers and drug pricing reform advocates have told about the drug industry, there are perhaps few greater villains than Humira and its maker AbbVie.

Between 2012 and 2018, AbbVie upped the drug’s annual after-rebates cost from $19,000 to $38,000 in the US, with sticker prices now over $60,000 per year — increases that led to accusations of price gouging, most recently from Democratic presidential frontrunner Elizabeth Warren.

The main question was not whether it would work; it was if it would be safe.

The Medicines Company is out with new data on its LDL cholesterol drug inclisiran, and they confirm the first, tentative answers: Yes. They also keep MedCo on track for an imminent  FDA submission for one of the first RNAi therapies and a drug that could flip the cholesterol market. An EU application will follow in the first quarter of 2020.