Or­chard $OR­TX. Seres $MCRB. Ret­roSense (ac­quired by Al­ler­gan). With sev­er­al high pro­file ex­its un­der their belt, 4BIO Cap­i­tal is out to find more trail­blaz­ers to back in the drug R&D world.

The VC shop has raised $50 mil­lion in the first close of what it hopes to be a $150 mil­lion sec­ond fund at the end of next year. With a fo­cus on ad­vanced ther­a­pies — cell and gene ther­a­py, RNA-based ther­a­py, tar­get­ed ther­a­py, and the mi­cro­bio­me — they will de­vote 60% of the fund to Eu­ro­pean deals from their perch in Lon­don, while spread­ing the rest be­tween Japan and the US, go­ing in­to the Mid­west and the South for promis­ing ideas that might not have re­ceived as much love as those com­ing out of Boston.

Al­to­geth­er, 8 to 12 pri­vate com­pa­nies will re­ceive in­vest­ment from 4BIO Ven­tures II.

“With the gap in re­al com­mer­cial de­vel­op­ment of ad­vanced ther­a­pies over the last 20 years, there’s a lot of pro­grams, par­tic­u­lar­ly here in Eu­rope, that aca­d­e­mics have been sol­dier­ing on, on a shoe­string bud­get, push­ing their ideas and thoughts to a point where they can be in the clin­ic with­in a year, par­tic­u­lar­ly if they don’t suf­fer from the bot­tle­neck of man­u­fac­tur­ing,” Owen Smith, di­rec­tor of in­vest­ment, told End­points News.

While many suc­cess­es in ad­vanced ther­a­pies have been lim­it­ed to rare con­di­tions, main­ly of the reti­na, liv­er and bone mar­row — 4BIO wants to start tak­ing these cut­ting edge ap­proach­es to slight­ly more main­stream ap­pli­ca­tions, man­ag­ing part­ner Dmit­ry Kuzmin said.

“Our am­bi­tion for…Fund II is to try and bring these in­to what we jok­ing­ly call medi­um rare con­di­tions, and ba­si­cal­ly where we have to tack­le with treat­ing tens of thou­sands of pa­tients on a reg­u­lar ba­sis,” he said.

Hav­ing been at the fore­front of ad­vanced ther­a­pies in­vest­ment since 2010, the team of 9 (bol­stered by a 6-mem­ber ad­vi­so­ry board) is clear about just the kind of fron­tiers it’s keen on tack­ling in each of the fields it’s watch­ing, Kuzmin added.

That means gene ther­a­py in the brain, as well as ways to tone down, crank up or turn off gene ther­a­pies (4BIO has pre­vi­ous­ly in­vest­ed in op­to­ge­net­ics start­up Ret­roSense, but there’s al­so chemo­ge­net­ics, ther­mo­ge­net­ics, mag­ne­to­ge­net­ics, and so on).

With­in cell ther­a­py, 4BIO is look­ing for sol­id clin­i­cal and man­u­fac­tur­ing op­er­a­tions that can de­liv­er con­sis­tent and durable re­spons­es; for tar­get­ed ther­a­py it’s most in­ter­est­ed in pro­tein degra­da­tion and vi­ral ap­pli­ca­tions; and “ra­tio­nal en­gi­neer­ing” is the key word for their mi­cro­bio­me bets.

The LPs, which in­clude the Chil­dren’s Min­neso­ta among a group of fam­i­ly of­fices and in­sti­tu­tion­al in­vestors, have man­dat­ed a third of the fund be re­served to launch new star­tups.

Kuzmin en­vi­sions most­ly seed-stage and Se­ries A rounds, with the oc­ca­sion­al Se­ries B — and the more ad­vanced in clin­i­cal proof-of-con­cept, the bet­ter. “Our ide­al project is clear­ly a for­ma­tion deal that’s al­ready in the clin­ic,” he summed up.

Ex­pect some more de­tails soon on the com­pa­nies they reck­on are push­ing through the med­i­cines of to­mor­row as the first two in­vest­ments get un­der way.

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.