Arcturus’ ex-CEO triumphs, ousting board that ousted him

The curtain is falling on the epic drama between little San Diego biotech Arcturus and its former CEO Joe Payne. After months of harpooning each other with lawsuits in a war for control, Payne has prevailed.

At least that’s what we’re reading from a statement Arcturus published today, which announced that four board members are resigning: Stuart Collinson, Craig Willett, Daniel Geffken, and David Shapiro. This was the action Payne has been rooting for, as these four directors, he alleged, conspired against him — resulting in the firing of Payne this February. In particular, Payne said these guys engaged in activity that violated the rules established by the Israeli laws that govern its operations.

For some background, Payne was fired from the RNA medicines company for allegedly putting his own interests before Arcturus’. Payne rejected that assertion, and responded with demands for the company to hold an extraordinary general meeting to vote on an ouster of his own design. He wanted to trade out the four adversaries on the board with new faces: Magda Marquet, Peter Farrell, Andrew Sassine, and James Barlow.

According to Arcturus’ new statement, the company has voted in favor of Payne’s plans, forcing the old players out. The company’s stock is up nearly 14% on the news, trading at $6.93 per share as of press time.

Drama aside, Payne’s pick for the board include some of the biggest names in San Diego biotech. Marquet, founder and co-chair of Althea Technologies, is a well-known industry executive who’s been leading San Diego’s biotech community for a couple of decades. And Farrell is the founder and former long-term CEO and current chairman of ResMed, one of the largest medical device companies in San Diego.

It’s unclear what will happen now with Payne. Will he rejoin Arcturus after the new board settles in? We reached out to Payne, and will update you when we hear back.

The drawn out fight took a nasty turn when Arcturus launched a series of lawsuits against Payne, seeking damages and injunctive relief and detailing Payne’s multiple alleged misconducts. Those included operating a “lucrative side business during business hours” and attempting to transfer Arcturus’ IP for no apparent reason during his tenure, in addition to orchestrating a move to block Arcturus’ routine auditing activity.

But now, those lawsuits should be dropped. According to Arcturus’ statement, the settlement agreement included “mutual releases of all parties and the agreement by the company and Joseph E. Payne to terminate all pending litigation.”

Hopefully the next news we hear from Arcturus will be about the company’s science.

“We are pleased to have come together to reach this very positive outcome that allows Arcturus to move forward, focused on creating substantial value for all shareholders,” Payne said. “We warmly appreciate the continued support from our shareholders, and the encouragement to reach an amicable resolution through this agreement. The company has accomplished a great deal in the last five years, and I’m confident that with the strong leadership of the board and management team, the best days are ahead for Arcturus.”

https://bit.ly/2IYRWuK

Evolus target hiked by JMP after exec hirings

Evolus price target raised to $30 after executive hirings at JMP Securities. After Evolus (EOLS) announced that it hired Lauren Silvernail, formerly the CFO at Revance Therapeutics (RVNC), to be its own CFO, JMP Securities analyst Donald Ellis noted this was the second hiring by the company of a C-suite executive from a major competitor after the company had previously hired CEO David Moatazedi from Allergan (AGN). The analyst, who contends that both Moatazedi and Silvernail “have voted with their feet for the winner in the aesthetic toxin market,” increased his view of the probability of approval for DWP-450 to 100% from 80%, which drove up his price target on Evolus shares to $30 from $22. Ellis maintains his Outperform rating on Evolus.

https://bit.ly/2IYQX1S

Foyston, Gordon & Payne Long Walgreen: London Value Investor Conference 2018

We’re posting up notes from the 2018 London Value Investor Conference.  Next up is Stephen Mitchell and Bryan Pilsworth of Foyston, Gordon & Payne who pitched two longs: Transcontinental (TSE:TCL) and Walgreens Boots Alliance (NASDAQ:WBA).

Stephen Mitchell & Bryan Pilsworth’s London Value Investor Conference Presentation

Long: Walgreen Boots Alliance (NASDAQ: WBA):  The shares are cheap because it’s rumoured that Amazon is going to enter the pharmacy business.  70% of prescriptions are recurring. 85% of prescriptions are generic.  People with recurring prescriptions may chose Amazon home delivery. Pharmacies may lose foot traffic which will impact brick and mortar store sales.

Walgreens is the largest retail pharmacy, health and daily living destination across the US and Europe. Market Cap $63bn. Global sales of $118bn, over 13,200 stores in 11 countries. Over the last 10 years, sales and EPS growth of 8%. Average ROE of 16%.  Two reasons why pharmacy/ store networks have a moat against Amazon.  1. Convenience: 70% of seniors chose pharmacy over mail order due to convenience.  2. Compliance: Managed Care Operators (MCOs) need pharmacies to ensure proper patient drug usage.  So far chains have taken share at the expense of mail order and independents.

High margin beauty products provide an opportunity to improve front-of-store sales and expand margins. Customers like in-store demonstrations before purchase. On-line sales are only 8% but growing.  Walgreens already has an omni-channel offering – a multi-channel sales approach – and a mobile offering. The mobile channel has 88m users in the US. Half of digital sales come through mobile. 50% of users use an app in-store. 20% of users are 55 years or older.  PE 10.3x CY 2018; ROE 19.8% CY 2018; Net debt / EBITDA 1.5x; dividend yield 2.5%.

https://bit.ly/2shV6mS

Adrian Warner Long HCA Healthcare: London Value Investor Conference 2018

We’re posting up notes from the 2018 London Value Investor Conference.  Next up is Adrian Warner of Avenir Capital who pitched long HCA Healthcare (NYSE:HCA).

Adrian Warner’s London Value Investor Conference Presentation

Prior to founding Avenir Capital in 2011 Adrian Warner worked in private equity.

Long: HCA Healthcare (NYSE: HCA):  HCA is a private hospital provider in the US with 179 hospitals, 38K staff, 47K beds. It has a strong  financial track record of growing revenue and margin stability. Margins have averaged 19% for over  20 years. It has leveraged 5% annual revenue growth into 15% annual EPS growth.

The bulk of the industry is not-for-profit hospitals or state/ local govt owned. Only 20% of hospital are for-profit in the US. In terms of inpatient costs per day for-profit hospitals have 24% lower costs, than not-for-profit. HCA is the dominant hospital provider in the for-profit sector with x2 the market share of the nearest competitor, Tenet Healthcare (THC). HCA’s scale and geographic focus provide a competitive advantage. It focuses on large urban markets which allows a greater focus on high-end subscribers. It has also focused on the sunbelt states which have large elderly populations.

Its industry leading capex allows it to attract the best physician groups. Its competitive advantage is demonstrated by long-term margin superiority, 19% Vs 10% for the industry average.  The hospital sector is expected to grow at around 6% per year. Even though there is a lot of regulatory noise, the Republicans failed attempts to pass health care reform in 2017 – with a majority in both houses – shows that radical change in the sector is unlikely.

HCA has grown through acquisition. The CEO believes the pipeline for potential acquisitions is good. Weak competitors provide M&A opportunities. HCA has bought back 20% of its shares since 2013.  EBITDA 7.7x; PE 10.7x; FCF yield 5.5%.

Be sure to check out the rest of the presentations from the London Value Investor Conference 2018.

https://bit.ly/2Jf1vc9

One shot may block chemo pain for several weeks

It might be possible to relieve the persistent pain that can follow chemotherapy with a natural protein that blocks the underlying inflammation process in cells.

Could one injection counteract chemotherapy-induced pain for months?

This was the conclusion of new research that tested the effects of a protein, called apolipoprotein A-I binding protein (AIBP), in mice with chemotherapy-induced pain.

Should the approach prove to be effective in humans with chemotherapy pain, it could offer an alternative to opioids, which carry the risk of addiction.

A report on the new study — led by the University of California (UC) San Diego in La Jolla — is now published in the journal Cell Reports.

It describes how one spinal injection of AIBP alleviated chemotherapy-induced pain in mice — without side effects — for 2 months.

Blocks underlying pain mechanism

AIBP binds to a cell surface protein called toll-like receptor 4 (TLR4) that plays a key role in recognizing infection and activating the immune system.

The researchers found that AIPB switched off the mice’s TLR4 receptors, effectively preventing and reversing inflammation and cell processes that deal with pain.

“What’s so special,” says study author Tony L. Yaksh, who is a professor in the Department of Anesthesiology at UC San Diego School of Medicine, “about our new approach, inhibiting the TLR4 receptor with AIBP, is that it actually modifies the pain processing systems themselves.”

He explains that most pain medications, including opioids, work by “dampening” perception of pain without actually switching off its source, which remains active.

In addition, opioids “impart a feeling of pleasure, which leads to their misuse and addiction,” he adds.

He and his colleagues found that AIBP actually blocks “the underlying mechanism that causes pain” — it does not just “mask the symptoms.”

The “misuse and addiction to opioids” that has followed their widespread use — including those prescribed for pain relief — is a “serious national crisis” in the United States.

Chemotherapy pain

Pain is a common side effect of cancer treatment that can significantly impair quality of life — for example, by reducing job opportunities and damaging mental health.

One of the side effects of chemotherapy is a persistent, painful condition that damages the nerves so that even the “lightest touch” can cause pain.

Cancer survivors may also find themselves living with persistent pain as a result of radiotherapyand surgery.

Prof. Yaksh says that around 39 percent of the 1.7 million people in the U.S. who are diagnosed with cancer every year experience pain as a result of the disease or its treatment.

He estimates that the national burden of morphine or its equivalent for this number of cancer patients — assuming that a typical patient takes around 100 milligrams per day for 12 months — amounts to some 24,000 kilograms per year.

Mechanism of inflammation, nerve damage

Scientists once thought that inflammation and nerve damage occurred separately.

However, in earlier work, Prof. Yaksh and colleagues found that sometimes, in a cellular process that involves TLR4, inflammation can result in persistent pain while exhibiting features of nerve damage.

In the new study, they carried out experiments in which they discovered that, by binding with TLR4, AIBP “selectively regulates” the removal of cholesterol from “lipid rafts.”

Lipid rafts are regions of cell membranes that have high concentrations of cholesterol and are important for helping cells communicate with each other and their surroundings.

Giving spinal injections of AIBP to mice with chemotherapy-induced pain effectively decreased the lipid rafts in the microglia cells of the animals’ central nervous system.

The injections also reduced other cellular events in the spinal cord, such as TLR4 activity, microglial activity, and inflammation.

Potential alternative to opiates

The researchers found that one AIBP spinal injection “completely reversed” chemotherapy-induced pain in the mice — without altering the animals’ “motor functions” — and that the effect lasted for 2 months.

They conclude that their findings reveal a mechanism through which AIBP can alter inflammation of nerve cells and suggest that it may have potential as a treatment for “pre-existing pain states.”

They are already working on alternative ways to administer AIBP systemically. However, they suggest that most people would probably choose to have an injection in their spine “every few months” rather than live with persistent pain.

An important implication is that AIBP could be developed as an alternative to high-dose morphine for those with “unremitting severe pain.” This would reduce use of opioids and the opportunity for misuse.

Prof. Yaksh points out that they are not suggesting that opiates should be dropped as a treatment for persistent pain; “that would be a tragedy,” he notes.

“But it would also be a greater tragedy if we didn’t support work to find a substitute for systemic opiates … if for no other reason [than] to reduce [their] presence in our society.”

Prof. Tony L. Yaksh

https://bit.ly/2sgaAba

Philadelphia’s first medical marijuana dispensary to open this week

Meeting its goal with one day to spare, Restore Integrative Wellness Center is opening Philadelphia’s first medical marijuana dispensary on Wednesday.

The center is in the city’s Fishtown neighborhood on Frankford Avenue across from the Fillmore. The 5,000-square-foot dispensary is in a renovated building that dates back to the 1870s and was previously a welding shop.

The company had set a goal of opening the dispensary in May.

The dispensary will have products from all five Pennsylvania medical marijuana growers.

Restore’s initial hours of operation will be Monday through Saturday from 11 a.m. to 5 p.m. Its product offering will encompass of variety of products from all five of Pennsylvania’s operational medical marijuana growers.

“Our mission is to be a friendly and reliable source of medical marijuana,” the company said in a statement.

The lobby of the Fishtown dispensary features a green wall.

Restore is led by co-owner Steven O, who is also the owner and operator of Reboot Integrative Wellness Center. Reboot has offices in Chinatown and Elkins Park. Other Restore owners include Vipul Patel, the company’s COO, and Dimple Thakrar, marketing director.

The company plans to open a second location in Elkins Park this fall. It has not yet decided on a site for its third dispensary allowed under its permit, according to Restore spokesman Jonathan Monk.

This spring has been was a busy month for medical marijuana dispensaries in southeastern Pennsylvania.

• In late April, TerraVida Holistic Centers opened Montgomery County’s first dispensary in Abington.
• Earlier this month, two other dispensaries started filling medical marijuana prescriptions when Illera Healthcare opened a site in Plymouth Meeting, and Keystone Shops opened a site in King of Prussia.
• Also in May, Beyond/Hello open a medical marijuana dispensary in Bristol, Bucks County. Beyond/Hello expects to open the first dispensary in Center City Philadelphia on the 1200 block of 1206 Sansom St. this fall.

The new dispensaries joined existing facilities that opened during the first quarter of the year in Devon (Keystone Shops), Sellersville (TerraVida) and Phoenixville (Cure Pennsylvania).

https://bit.ly/2sgeUaf

Reverse aging by removing wrinkles inside our cells?

A new discovery about the effects of aging in our cells could allow doctors to cure or prevent diabetes, fatty liver disease and other metabolic diseases—and possibly even turn back the clock on aging itself.

The new finding from the University of Virginia School of Medicine suggests that fatty liver disease and other unwanted effects of aging may be the result of our cells’ nuclei—the compartment containing our DNA—getting wrinkly. Those wrinkles appear to prevent our genes from functioning properly, the UVA researchers found.

There’s no wrinkle cream for nuclear membranes, but there is a tantalizing possibility: We might use viruses to smooth the membranes’ surfaces—and restore the cells to functioning as they did in the glow of youth.

Lumpy Membranes

The new discovery from the lab of Irina M. Bochkis, Ph.D., of UVA’s Department of Pharmacology, shows that the location of our DNA inside the cell’s nucleus is critically important. Genes that are turned off are shoved up against the nuclear membrane, which encases the nucleus. But with age, our nuclear membranes become lumpy and irregular, and that prevents genes from turning off appropriately.

“We have the same DNA in every single cell but each cell is different,” Bochkis explained. “So how does that work? Well, actually, certain genes need to be on in the liver and they have to be turned off in the brain, for example, and vice versa. If they’re not turned off appropriately, then you have problems.”

Looking at a model of fatty liver disease, Bochkis found that our livers become studded with fat as we age because of the wrinkly nuclear membranes. “When your nuclear membrane is no longer functioning properly, it can release the DNA that’s supposed to be turned off,” she said. “So then your little liver cell becomes a little fat cell.”

The accumulation of fat inside the liver can cause serious health effects, increasing the risk of type 2 diabetes and cardiovascular disease, even potentially leading to death. “The liver can end up looking like Swiss cheese,” Bochkis said.

The membrane wrinkling stems from a lack of a substance called lamin, a cellular protein that comes in various forms. By putting the appropriate lamin back, we might smooth out the membrane, like Retinol helps smooth face wrinkles.

Getting it there is the challenge. But Bochkis has an idea: We could use viruses to deliver the shipment. Scientists are already modifying viruses for beneficial medical purposes, and it would be particularly easy to get a modified virus to the liver because of the organ’s role in detoxifying the body. And if it works? “You’re going to have normal cells—normal, healthy cells—and they will appropriately express the genes that should be expressed and … you’re going to eradicate the stuff that shouldn’t be there,” she said.

Bochkis suspects the wrinkling of the nuclear membrane is responsible for unwanted effects of aging in other parts of the body as well. “Every time I give this talk to colleagues, they say, ‘Well, do you think this is a universal mechanism?'” she said. “In my opinion, I think it is.”

 Explore further: Codependence of cell nucleus proteins key to understanding fatty liver disease

More information: Holly Whitton et al, Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver, Aging Cell (2018). DOI: 10.1111/acel.12742

https://bit.ly/2L57RbH