Orchard files for $173M IPO to run pivotal gene therapy trials

Orchard Therapeutics has filed to raise $173 million (€150 million) in an IPO. The offering will give the GlaxoSmithKline-backed biotech the means to take three gene therapies through the clinic and onto the market.

Transatlantic biotech Orchard established one of the broadest clinical-phase gene therapy pipelines in the industry earlier this year when added GSK’s portfolio to its existing assets. Orchard followed up on the GSK deal with a $150 million series C to support its mushrooming pipeline. And, as hinted at by the involvement of Deerfield Management in the series C, it has now filed to go public.

With Orchard having close to $200 million in cash following the series C, the planned $173 million will put it in a strong position financially. Orchard wants to secure such a war chest to set it up to run pivotal trials of three gene therapies and file for approvals of them on both sides of the Atlantic.

OTL-101 and OTL-200 look set to be the first two Orchard gene therapies to land on regulators’ desks. Orchard plans to file for FDA approval of OTL-101 in the immune system disorder ADA-SCID in 2020, and seek clearance to sell neurometabolic disorder gene therapy OTL-200 in Europe the same year. A European filing for OTL-101 and U.S. submission for OTL-200 will follow later.

Those two gene therapies are advancing down the pipeline just ahead of OTL-103, a treatment for a rare disease that affects the immune system and platelets. Orchard expects to file for approvals of OTL-103 in the U.S. and Europe in 2021.

Orchard is warning investors that factors including regulatory decisions could set back its plans. The biotech is yet to get definitive feedback on its move from academic to commercial manufacturing. The academic process has caused some problems, with two patients suffering serious adverse events potentially linked to it, but Orchard will need to convince regulators of the comparability of the two production methods. Failure to do so could lead to demands for more clinical data.

If Orchard pulls off the plan, it will close out 2021 with four approved gene therapies. The fourth, Strimvelis, is an ex-GSK drug that has been on the market in Europe since 2016. Strimvelis had a very slow start commercially and could be superseded by OTL-101, which targets the same indication. The deal with GSK tasks Orchard with keeping Strimvelis on the market until an alternative is available.

https://www.fiercebiotech.com/biotech/orchard-files-for-173m-ipo-to-run-pivotal-gene-therapy-trials

Arena preparing for trials of first-in-class heart failure drug

Arena Pharma has a new drug candidate heading for clinical trials next year that it says could be a first-in-class option for decompensated heart failure (DHF).

The selective beta-3 adrenergic receptor antagonist—called APD418—was revealed at Arena’s R&D update in New York yesterday and is described by the company as a first-in-class calcium-independent myofilament derepressor that could be a “better and safer” option for heart failure patients.

Medical therapy hasn’t much changed for DHF in decades and—with more than a million hospitalizations for DHF every year—there is an urgent need for new treatment options that can keep patients out of hospital and treatment costs down.

Right now, there are no approved treatments proven to improve outcomes in DHF, according to Arena, and for many patients the only option is to use positive inotropes, drugs such as dobutamine and milrinone that push the heart muscle to pump more strongly. However, these drugs can increase the risk of death and have serious side effects such as low blood pressure and irregular heartbeats.

Arena’s chief medical officer Preston Klassen, M.D., explained that the beta-3 receptor is expressed more often in failing hearts and seems to suppress the contractility of heart muscle as a defense mechanism, protecting it from efforts by the sympathetic nervous system to keep the heart flogging away to maintain blood pressure.

Because it blocks beta-3 selectively, APD418 should be able to increase heart contractions without the acceleration in heart rate and elevated blood pressure that accompanies current drugs that also affect the beta-1 and beta-2 adrenergic receptors.

“The idea is that we can block the negative impact on contractility by antagonizing the receptor—essentially remove the brake—and actually increase cardiac performance in a safer environment,” according to Klassen. “Doing that would be unique…and has not been achievable to date,” he said.

The hypothesis has been tested in animal models and now Arena says it is preparing to file for approval to start clinical testing of APD418 in 2019.

Arena also outlined the trial designs and timings for its upcoming phase 3 trials for drugs already in clinical development. That includes S1P receptor modulator etrasimod, which is due to start late-stage testing in ulcerative colitis and Crohn’s disease as well as new indication atopic dermatitis next year.

Oral prostacyclin receptor agonist ralinepag is already in one phase 3 trial in pulmonary arterial hypertension (PAH) looking at exercise capacity and will start two more trials in 2019 that should provide data on cardiovascular outcomes at the time of filing—proposed for around the second half of 2021.

Arena also said it will move its cannabinoid receptor type 2 (CB2) agonist olorinab into additional phase 2 trials in gastrointestinal pain associated with Crohn’s disease and irritable bowel syndrome after reporting proof-of-concept data last month.

https://www.fiercebiotech.com/biotech/arena-preparing-for-trials-first-class-heart-failure-drug

Einhorn on Tesla: ‘Like Lehman, we think the deception is about to catch up’

Hedge fund manager David Einhorn is blasting Tesla again.

The investor compared Tesla to his most famous and prescient bearish call on Lehman Brothers during the financial crisis nearly a decade ago.

“Like Lehman, we think the deception is about to catch up to TSLA,” Einhorn said in an investor letter Friday. “Lehman threatened short sellers, refused to raise capital (it even bought back stock), and management publicly suggested it would go private. Months later, shareholders, creditors, employees and the global economy paid a big price when management’s reckless behavior led to bankruptcy.”

In May 2008, just a few months before Lehman Brothers declared bankruptcy, Einhorn said at the Ira W. Sohn Investment Research Conference that the investment bank was a risk to the financial system and questioned its accounting. He confirmed his firm Greenlight was short Lehman during that speech.

Shares of Tesla, which were already down Friday in light of CEO Elon Musk’s tweets mocking the Securities and Exchange Commission, dropped 6.5 percent following news of Einhorn’s letter.

Musk has taunted short sellers in the past on social media, including Einhorn.

https://www.cnbc.com/2018/10/05/einhorn-on-tesla-like-lehman-we-think-the-deception-is-about-to-catch-up-to-tsla.html

Pyxus: ‘Better Growth Prospects, Cheaper Valuation Than Tilray, Canopy Growth’

Pyxus (“PYX”) has better growth prospects and significantly more shots on goal than other cannabis companies.

We believe PYX has between 500 and 1,600% upside potential.

PYX recently held an analyst day indicating an EBITDA target of +/- $500m in fiscal 2023.

PYX is being mispriced as the market underestimates the resiliency of the legacy leaf tobacco business, which generates ~ $175m in adjusted EBITDA.

PYX has outstanding growth opportunities not only in legal cannabis, but also in other fast-growing, potentially large markets like industrial hemp/CBD and e-liquids for vaping products.

https://seekingalpha.com/article/4209928-pyxus-international-better-growth-prospects-cheaper-valuation-tilray-canopy-growth

Roche Hemlibra breaks into wider hemophilia market with blockbuster OK

Roche’s Hemlibra officially has the hemophilia indication it’s been waiting for—and that its competitors have been dreading.

On Thursday, the FDA approved the drug to treat hemophilia A patients without factor VIII inhibitors, putting a significantly larger group of patients in line for Hemlibra therapy. Previously, the drug was cleared only in patients with inhibitors, which develop as patients use factor VIII replacement drugs to prevent bleeding.

Now that the drug has a green light in all U.S. hemophilia A patients—who number between 10,000 and 12,000, according to estimates provided by Roche—analysts expect its sales to soar. Industry watchers predict Hemlibra could rack up $2 billion by 2025, though some analysts have said that number could climb far higher. Jefferies analysts, for their part, have pegged 2025 sales at $5 billion.

One reason? Efficacy. In a phase 3 study in hemophilia A patients without factor VIII inhibitors, Hemlibra reduced bleeding incidents that needed treatment by 96% compared with no preventive therapy, Roche said in May. Hemlibra also boasts a convenience advantage: It can be administered subcutaneously every week, two weeks or four weeks.

But Hemlibra’s prospects don’t bode well for Shire, which entered the hemophilia sphere with its $32 billion Baxalta deal back in 2016. The company’s shares have been taking a beating throughout Hemlibra’s rise, and Thursday’s new approval sent them south once again.

Investors concerned about Shire’s ability to keep up with Roche in the hemophilia field have also hounded Takeda, which inked a $62 billion buyout agreement for Shire back in May. But the Japanese drugmaker’s executives have worked to reassure investors that the company has already factored that next-generation competition into its financial forecasts.

https://www.fiercepharma.com/pharma/roche-s-hemlibra-breaks-into-wider-hemophilia-market-blockbuster-approval

Gilead strikes discount Yescarta deal with NHS in adults

Gilead Sciences has one-upped Novartis in England’s CAR-T market. The drugmaker reached a deal with NHS England on Yescarta, beating rival Kymriah to become the first CAR-T therapy available to adult blood cancer patients on England’s public health system, albeit via the Cancer Drugs Fund.

The National Institute for Health and Care Excellence (NICE) had in August rejected Yescarta because its price didn’t meet the agency’s cost-effectiveness metrics. But now, NICE has come around to back its use under NHS England’s Cancer Drugs Fund—after a confidential discount off the £300,000 full list price.

The fund, managed by NICE, which operates under NHS England, serves as an extra means for patients to access novel medicines early before a full NICE backing.

With this deal, an estimated 200 patients a year will be eligible for the treatment, according to NHS England. These are adult patients with diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) who have failed at least two prior therapies.

In the clinical trial that led to Yescarta’s EU approval in late August, 72% of patients responded to it, and half of them remained cancer-free six months after treatment.

However, almost at the same time Yescarta won EU clearance, NICE gave its thumbs-down to the drug, citing the lack of direct clinical data that compare Yescarta with standard salvage chemotherapy. Though the agency recognized Yescarta as “a step-change in treatment,” the cost police concluded that Yescarta’s price was too high to be considered cost-effective.

Whatever discount Gilead offered to get a deal now, it is obviously enough to win partial endorsement from NICE in adult patients, which rival Novartis’ Kymriah doesn’t have. After stiff-arming Yescarta, NICE in September approved Kymriah at a list price of £282,000, but only in children and young adults with acute lymphoblastic leukemia.

Then, Kymriah’s hope to reach England’s adult patients was also nixed by NICE for the same reason Yescarta faced—it’s too expensive because no data against salvage chemo is available to gauge the drug’s benefit.

Yescarta is currently leading Kymriah in sales. In the first half of 2018—when neither drug had won an EU nod—the Gilead drug sold $108 million in the U.S. But with Kymriah’s second FDA nod in DLBCL in May, the two drugs are now officially vying in the same indication.

https://www.fiercepharma.com/pharma/beat-you-to-it-kymriah-gilead-strikes-yescarta-deal-nhs-england-at-discount

GW Pharma looks to dispel cannabis stigma with Epidiolex launch

Set to roll out the U.S. market’s first prescription cannabidiol soon, GW Pharmaceutical will be looking to assure doctors that Epidiolex, approved to treat rare forms of epilepsy, is vastly different from off-the-shelf artisan oils at cannabis shops.

To that end, GW has hired 66 neurology sales representatives who will target some 5,000 epilepsy specialists in the U.S., Stephen Schultz, VP of investor relations, said. Their message? Trust the science and rigor behind the only FDA-approved CBD.

“We’re the leader in this area, we’re science-based, and we believe physicians and patients will desire medicines that have gone through the FDA review process. When a drug is prescribed that’s FDA approved, you know it’s exactly the same every time it’s prescribed and every time it’s taken,” Schultz said.

Epidiolex was initially approved in June, but it had to wait until last week for the Drug Enforcement Agency to figure out how to handle the plant-derived cannabidiol CBD. The good news for GW was a rescheduling from a Schedule I drug—others in that class include heroin and marijuana—to a Schedule V, the class considered to have the least potential for abuse. That class includes medicines such as Robitussin AC and Pfizer’s Lyrica.

Two websites, one directed at physicians and the other at patients, will back the launch, although Schultz characterized the marketing as a “medically oriented education commercialization effort” directed at professionals.

Along with the launch of Epidiolex to treat seizures associated with Lennox-Gastaut syndrome or Dravet syndrome epilepsies, GW plans to continue to trial the drug for other uses. It currently has a single phase 2 study, due to read out next year, testing the drug as a treatment for seizures in tuberous sclerosis complex.

Schultz said GW’s own clinical experience also suggests promise for Epidiolex for treatment of autism spectrum disorders, and the company plans to launch a new study in Rett Syndrome in the fourth quarter.

https://www.fiercepharma.com/marketing/gw-pharma-cannabidiol-epidiolex-market-rollout-looks-to-dispel-stigma-and-promote-product