What’s Next For For Applied Genetic After 50% Plunge?

Applied Genetic Technologies Corp AGTC 47.14%, a biotech focused on adeno-associated virus-based gene therapies for the treatment of rare diseases, reported disappointing results from an X-linked retinoschisis clinical study.

The company also confirmed Biogen Inc BIIB 0.77% terminated its partnership effective March 8.

The Analysts

H.C. Wainwright & Co’s Joseph Pantginis maintains a Buy rating on Applied Genetic Technologies’ stock with a price target lowered from $8 to $5.75.

Wedbush’s David Nierengarten maintains at Outperform, price target lowered from $12 to $11.

BMO Capital Markets’ Matthew Luchini downgrades from Outperform to Market Perform, price target lowered from $13 to $5.

HC Wainwright: Here’s What Happened

Applied Genetic’s XLRS clinical study consisted of 27 patients. The 13 who received a high dose showed no improvements, with just two patients showing improvements in one of the four endpoints, OCT, Pantginis said in a research report. Zero pediatric patients at the middose showed efficacy at any endpoint, he said.

Given the disappointing announcement, investor confidence has taken a hit and the company is now entering a “show me stage,” the analyst said.

The bullish case for the stock can still be made, as there are some differentiating factors between the reported XLRS programs and XLRP programs, Pantginis said:

• XLRS included intravitreal injections and was dosed into a highly heterogeneous population.
• The XLRP programs are dosed in subretinal fashion.

Wedbush: Silver Lining In Biogen Announcement

Applied Genetic’s Biogen termination announcement has a “silver lining,” as the company now has full rights to the XLRP gene therapy program, which is seen as a primary value driver, Nierengarten said in a research report.

Biogen previously controlled worldwide rights to the XLRS program and Applied Genetics merely received a low-teens royalty payment, the analyst said.

Applied Genetic is now positioned to benefit from more upside in the XLRP program, which boasts multiple advantages over XLRS, Nierengarten said:

• A larger market.
• Better-defined biology through validated higher order animal models.
• Clinical POC established by other sponsors.
• Superior benefits of subretinal delivery.

On the flipside, Applied Genetics will likely need incremental financing to proceed, but there is nevertheless a “positive path forward” with its XLRP opportunity, according to Wedbush.

BMO: Negative Signal From Biogen

Although the return of full rights related to XLRP from Biogen is a positive development for Applied Genetic, the fact that Biogen decided to return rights ahead of proof-of-concept data — which is expected in the third quarter of 2019 — is a “negative signal,” Luchini said in the downgrade note.

This also implies incremental risk to the company’s success in XLRP, for which BMO lowered its probability of success from 15 percent to 10 percent, the analyst said.

https://www.benzinga.com/analyst-ratings/analyst-color/18/12/12846465/sell-side-roundup-whats-next-for-for-applied-genetic-af

Raymond James: Lannett Emerges From Levothyroxine Woe

Lannett Company, Inc. LCI 3.23% announced the amendment of its Senior Secured Credit Facility Term A loan of $275 million, which takes the company a step closer to emerging from debt following the loss of generic levothyroxine, according to Raymond James.

The Analyst

Analyst Elliot Wilbur maintains a Market Perform rating on Lannett.

The Thesis

Although the modification of the original Term A loan doesn’t change the cash outflow profile of principal obligations related to the loan, it “slightly loosen the shackles on the company” and “should afford ample ceiling well through loan maturity in 2020,” Wilbur said in a note. (See his track record here.)

Lannett’s management projects the company’s adjusted EBITDA for fiscal 2020, or the 12 months ending September 2020, significantly ahead of Street estimates.

The company expects the 16 products that it has launched so far in 2018 to generate $75 million in revenue with margins of 35-40 percent through June 2019. the analyst said.

Further, the company plans to launch another 15-17 products by the end of fiscal 2019. These would mostly be internally developed products with equally high margins and a market value exceeding $5 billion, according to Raymond James.

The drug gConcerta is likely to be a near-term catalyst, with a GDUFA date of Feb. 1, 2019, Wilbur said.

Sometime next year, more news should arrive from the FDA and the management on Numbrino — topical cocaine — which received a CRL in July, the analyst said.

https://www.benzinga.com/analyst-ratings/analyst-color/18/12/12847495/raymond-james-lannett-emerges-from-levothyroxine-woes

Akebia Poised To Be ‘Renal Powerhouse’ With Keryx Merger: Raymond James

Akebia Therapeutics Inc AKBA 2.91% announced shareholder approval this week for its merger with Keryx Biopharmaceuticals KERX 0.45%.

The Analyst

Analyst Reni Benjamin of Raymond James maintains an Outperform rating on Akebia and raised the price target from $18 to $21.

The Thesis

The proposed merger of Akebia and Keryx has received approval from the shareholders of both companies.

The merger is accretive to Akebia and creates a “one-stop shop in the renal space,” Benjamin said in a note. (See his track record here.)

The combined entity could generate revenues of around $202 million and $417 million in 2018 and 2019, respectively, the analyst said. Revenue could potentially reach close to $1 billion by 2026, he said.

Hydroxia inducible factorprolyl hydroxylase (HIF-PH) inhibitors have shown positive clinical data, and multiple Phase III trial readouts for vadadustat are expected over the next 24 months, Benjamin said.

Akebia has a strong cash position and several partnerships in place, he said.

The company may not require additional equity financing in the near future, with Auryxia sales and revenue from various partnerships likely offsetting expenses from the ongoing Phase III studies of vadadustat, according to Raymond James.

Auryxia is expected to generate revenue of $108 million in 2018 and $160 million in 2019, and this may increase to $309 million by 2026, Benjamin said. The analyst Benjamin expects vadadustat to enter the market in the back half of 2021 and potentially generate revenue of $606 million in 2026.

https://www.benzinga.com/analyst-ratings/analyst-color/18/12/12847726/akebia-poised-to-become-renal-powerhouse-with-keryx-mer

Anti-Opioid Vaccine Shows Promise in Animal Tests

 A vaccine that might help combat the opioid epidemic has performed well in early animal testing, researchers report.

The vaccine contains antibodies that are effective against several synthetic opioids, including fentanyl and the even deadlier carfentanil.

Tests in mice showed that the vaccine blocked the pain-numbing effects of synthetic opioids and also protected the mice against overdose from the drugs, according to researchers at The Scripps Research Institute in La Jolla, Calif.

Of the estimated 72,000 drug overdose deaths in the United States in 2017, about 30,000 were caused by synthetic opioids, the study authors said.

Because research with animals often doesn’t yield the same results in humans, the investigators have started to develop human antibodies to synthetic opioids, and the team plans to test their effectiveness in the future.

“When it comes to the very powerful opioid carfentanil, the current treatment for this opioid’s induced lethality does not work very well — it has no staying power,” said study leader Kim Janda.

“Antibodies persist longer, and thus have enormous promise for addressing both opioid addiction as well as overdose,” he added in a news release from the American College of Neuropsychopharmacology.

Along with protecting drug users, this type of vaccine might protect people at risk from contact with synthetic opioids, such as first responders, the study authors suggested.

“These antibodies could be used to protect police, EMTs and other first responders from inadvertent acute fentanyl exposure,” Janda said. “A canine version might even one day be used to protect drug-sniffing dogs.”

The findings were scheduled for presentation Dec. 13 at the annual meeting of the American College of Neuropsychopharmacology, in Hollywood, Fla. Until published in a peer-reviewed journal, research presented at meetings should be considered preliminary.

More information

The U.S. Department of Health and Human Services has more on the opioid epidemic.

SOURCE: American College of Neuropsychopharmacology, news release, Dec. 13, 2018

https://consumer.healthday.com/bone-and-joint-information-4/opioids-990/anti-opioid-vaccine-shows-promise-in-mice-740471.html

AHA: The Eyes Have It for High Blood Pressure Clues

When Dr. William White shines a bright light in his patient’s eye, he’s looking for more than just vision problems.

He’s searching for clues indicating the effects of high blood pressure, or hypertension, and what he finds could help prevent heart attacks, strokes and other serious health problems far beyond the eye.

“We can see changes due to vascular conditions caused by diabetes or hypertension,” said White, an optometrist with Baylor Scott & White Health in Temple, Texas. “The blood vessels in the retina can become a little more stiff and hardened. They’ll push on each other and cross, like two hoses in a confined space.

“When it gets really bad, we’ll see some of the blood vessels start to leak, we’ll see some hemorrhaging. And that can cause a whole range of vision issues.”

Vision symptoms may not show up for years. But ultimately, high blood pressure can result in hypertensive retinopathy, blood vessel damage causing blurred vision or loss of sight; choroidopathy, a buildup of fluid under the retina that can distort or impair vision; or optic neuropathy, a blood flow blockage that can kill nerve cells and cause vision loss.

Similarly, high blood pressure may not reveal itself for decades before causing a heart attack or stroke, which earns its grim description as the “silent killer.”

That is why detecting high blood pressure early and treating it with diet, exercise and medication is crucial, and why White says eye doctors are on the front lines of the battle.

“Sometimes people will say, ‘I’m just here to get my glasses. Why are you checking my blood pressure?'” he said. “We try to inform them about the unique opportunity we have to look at these blood vessels in the eye.”

A 2013 study reported in the journal Hypertension underscored the point. Researchers checked about 2,900 patients with high blood pressure for hypertensive retinopathy, then tracked them for an average of 13 years. They found that those with a mild form of the condition had a 35 percent greater risk of stroke. That increased risk leaped to 137 percent for those with moderate or severe hypertensive retinopathy.

Although more research is needed to confirm the findings regarding stroke risk, White has no doubt about the crucial role of eye doctors to educate patients about the need to control blood pressure.

“You’re not just a pair of eyeballs walking into an exam room,” he said. “We have to look at the entire person and the whole picture. These are things that can impact their lives significantly, and we have a responsibility for their overall health.”

But doesn’t every medical checkup start with a blood pressure check? And doesn’t every pharmacy have a machine to measure it yourself?

White said many people would be surprised how many of his patients rarely see another doctor, or if they do, don’t always follow medical advice or don’t take their blood pressure medication.

“Some people don’t go for a routine checkup every year,” he said. “They tell me, ‘Look, I just don’t like going to the doctor.’ But their eyes are a problem, so they’ll come to us.”

Knowing the risks of high blood pressure, White said, keeps him vigilant.

“It’s so important because of the silent nature of this problem,” he said. “People can feel absolutely fine, but high blood pressure has a cumulative effect. If it’s uncontrolled over years, it’s going to cause damage later in life.”

https://consumer.healthday.com/eye-care-information-13/eye-and-vision-problem-news-295/aha-the-eyes-have-it-for-high-blood-pressure-clues-740587.html

California Farm Implicated in Outbreak of E. coli Tied to Romaine Lettuce

Federal health investigators said Thursday that they’ve pinpointed at least one California farm implicated in the recent outbreak of E. coli illness tied to romaine lettuce, but they added that more farms are probably connected.

So far, 59 people across 15 states have come down with the often severe gastrointestinal illness. Health concerns were so high that just before Thanksgiving, the U.S. Food and Drug Administration and the U.S. Centers for Disease Control and Prevention asked Americans to temporarily stop consuming all romaine lettuce while they investigated the source of the outbreak.

That investigation has now uncovered at least one source, experts at the FDA and CDC said in a news briefing Thursday afternoon.

“One of the samples tested by the CDC was positive for the outbreak strain by genetic fingerprinting, and was found in the sediment of an agricultural water reservoir at one ranch that is owned and operated by Adam Brothers Farming in Santa Barbara County, Calif.,” said Dr. Stephen Ostroff, senior advisor to the FDA Commissioner.

He said the farm was cooperating with the investigation. The farm hasn’t shipped romaine lettuce since Nov. 20, and Ostroff said the farm is “committed to recalling products that may have come into contact with water from the agricultural water reservoir.”

That said, other farms in the area might still be implicated, so “people should still pay close attention to where their lettuce is from,” he added.

Because of this and other recent outbreaks, romaine lettuce now sold in the United States has labeling indicating the place and date of harvest. If heads of romaine are sold loose, without affixed labels, retailers are being asked to post a notice showing place and date of harvest near the store register.

Most romaine sold in the United States is safe to eat. Right now, precautions are limited to romaine lettuce from just a few California counties, the FDA said.

“We continue to advise avoiding romaine lettuce from Monterey, San Benito and Santa Barbara counties in California,” Ostroff said.

Hydroponically- and greenhouse-grown romaine also does not appear to be related to the current outbreak.

Illnesses from the E. coli O157:H7 strain implicated in this outbreak have sometimes been severe. Although no deaths have been reported, there have 23 hospitalizations and 2 cases of kidney failure, health officials said.

“The E. coli strain isolated from ill people in the current romaine lettuce outbreak is also closely related to the E. coli strain isolated from people in a 2017 outbreak linked to leafy green in the United States and romaine lettuce in Canada,” noted FDA Deputy Commissioner Frank Yiannas.

So who’s most at risk from E. coli?

Dr. Robert Glatter is an emergency physician at Lenox Hill Hospital in New York City who’s seen the effects of infection with the gastrointestinal bug firsthand. It’s not a minor ailment, he said.

“In general, symptoms of E. coli infection generally begin about three to four days after consuming the bacteria, and may include abdominal cramping, nausea, vomiting, and watery or bloody diarrhea, along with fever,” Glatter said.

And while healthy people who battle a bout of E. coli typically recover within five to seven days, the illness can be more protracted — and even deadly — for people already made vulnerable by chronic disease or advanced age.

“People with diabetes, kidney disease or those with cancer or autoimmune disease run the risk of a more severe illness,” Glatter explained.

The particular strain of E. coli detected in the current lettuce outbreak — E. coli O157:H7 — is particularly nasty, he noted.

“Most strains of E. coli do not actually cause diarrhea, but E. coli O157 produces a powerful toxin that injures the inner lining of the small intestine, leading to bloody diarrhea,” Glatter said. Even a tiny amount of ingested bacteria could spur this type of illness.

“It can make people much more ill, and may lead to hemolytic uremic syndrome, a type of kidney failure, in some cases,” he said.

In many cases, antibiotics are used to help beat back an E. coli infection, but these drugs can affect the kidneys, Glatter noted.

“Antibiotics may be necessary in certain cases, so it’s important to see your doctor if you have continued and severe symptoms such as fever, bloody diarrhea, and you are not able to eat or drink,” he said.

However, in the case of E. coli O157:H7, “taking antibiotics may actually increase your risk of developing kidney failure, so it’s important to speak with your health care provider if you should develop severe symptoms,” Glatter advised.

And if you do think you might be sick with E. coli, or any other foodborne illness, make sure you don’t spread it to those near you.

The bacterium “can be transmitted person-to-person, so it’s vital that anyone who is potentially infected wash their hands thoroughly and not share utensils, cups or glasses,” Glatter said. “This also goes for bath towels. Linens also need to be washed in hot water and treated with bleach.”

He noted that “ground beef, unpasteurized milk, fresh produce and contaminated water are common sources of E. coli bacteria.”

More information

Find out more about E. coli illness at the U.S. Centers for Disease Control and Prevention.

SOURCES: Dec. 13, 2018, news briefing, U.S. Food and Drug Administration and Centers for Disease Control and Prevention; Robert Glatter, M.D., emergency physician, Lenox Hill Hospital, New York City

https://consumer.healthday.com/public-health-information-30/e-coli-news-743/california-farm-implicated-in-outbreak-of-e-coli-tied-to-romaine-lettuce-740594.html

Phibro Animal Health: Aquaculture Acquisition to Create Vaccine Power

Phibro Animal Health Corporation announced it has acquired the assets of KoVax Ltd., an Israel-based developer and manufacturer of vaccines for the global aquaculture market. The acquisition strengthens Phibro’s position in fish vaccine innovation and expands its portfolio of aquaculture products.

KoVax’s research and development team has joined Phibro’s biological R&D team, and will focus on developing a pipeline of innovative vaccines for the aquaculture market. Phibro’s first commercial aquaculture vaccine is KoVax’s “KV3” vaccine, which helps prevent Koi Herpes Virus, a highly contagious disease that can cause significant mortality in common carp farms.

https://www.marketscreener.com/PHIBRO-ANIMAL-HEALTH-CORP-16253058/news/Phibro-Animal-Health-Aquaculture-Acquisition-to-Create-Vaccine-Innovation-Powerhouse-27751970/