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Thursday, February 28, 2019

After a Speedy IPO, Equillium Expands Antibody R&D to Renal Disease

Equillium, a biotech that’s looking to develop an antibody drug for immuno-inflammatory diseases, has added a form of renal disease to the indications for which it aims to develop medicines.
It’s the latest step in a fast-moving journey for the La Jolla, CA-based company, which raisedabout $65 million in an initial public offering in October just 19 months after its founding.
Headed by former Amylin CEO Dan Bradbury, Equillium (NASDAQ: EQ) has licensed the drug, itolizumab, which it calls EQ001, from Indian pharma giant Biocon Limited for development in the United States and Canada.
Equillium was formed to advance itolizumab, which had already undergone Phase 1 testing by Biocon in about 330 patients in Australia, as a treatment for acute and chronic graft-versus-host disease (aGVHD and cGVHD), a complication seen in transplant patients, and for a severe form of asthma.
On Tuesday, Equillium added lupus nephritis (LN), a kind of kidney damage often seen in patients with lupus—a chronic condition in which a person’s immune system attacks their own healthy tissues and organs—to the list of therapeutic areas in which it will study the drug.
Lupus affects five million people globally, with 16,000 new cases reported annually, according to the Lupus Foundation of America. The kidney inflammation characteristic of LN can eventually cause renal failure. No FDA-approved treatment exists; medications used to relieve LN symptoms, including corticosteroids and immunosuppression drugs, often come with side effects.
The condition is one of the most common and dangerous complications of lupus, according to Kenneth Farber, president and CEO of the Lupus Research Alliance, in the Equillium statement. Equillium says there are more than 100,000 LN Patients in the U.S.
The company plans to initiate a proof-of-concept trial for EQ001 as an LN treatment in the second half of this year, and says the data will inform future development of the drug in systemic lupus as well as a form of the disease that affects solely the skin.
The company also announced it would delay its plans for a Phase 2 trial of the drug in patients with cGVHD until data from a Phase 1b/2 aGVHD trial, slated to start in March with about 84 patients, is available: a move it described as a more “sequential” approach to its study of the drug in patients with GVHD. The FDA has granted EQ001 fast-track approval for the treatment of aGVHD and orphan drug status for the prevention and treatment of the condition.
Equillium also aims to launch a proof-of-concept trial in severe asthma sometime next quarter. The company is also eying gastrointestinal and neuroinflammation conditions as potential indications for EQ001 in the future.
The company said EQ001 targets a receptor called CD6 that modulates the activity of T-effector cells, which have been implicated in a broad range of immuno-inflammatory diseases. The aim is to dampen the activity of these cells.
The compound is the only one to which Equillium has rights, although Bruce Steel, Equillium’s president and chief business officer, said in an interview with Xconomy earlier this year that the company is actively looking for additional programs to in-license.
In that interview, the management team described how the company came together and how and why they took it from inception to IPO in less than two years.
Bradbury’s previous company Amylin, a San Diego developer of diabetes treatments, was acquired by Bristol-Myers Squibb (NYSE: BMY) in 2012 for $5.3 billion. Bradbury, who spent 18 years at Amylin and oversaw the launch of three medicines there, was subsequently recruited by Steel as the first advisor to an in-house venture fund Steel had started at BioMed Realty, a San Diego-based real estate investment trust (REIT). Previously, Steel was in the biotech industry, as an executive at San Diego’s Anaphore, a co-founder and CEO of Rincon Pharmaceuticals, and head of corporate development at Ambit Biosciences.
(BioMed was acquired in 2016 by private equity giant Blackstone for about $8 billion.)
Bradbury also joined the board of directors at Biocon, with which he had worked while at Amylin—a relationship that, a few years later, would prove serendipitous.
Equillium’s chief scientific officer, Stephen Connolly, joined the BioMed ventures team in 2016 following an introduction from Bradbury. It was Connolly, previously with San Diego biotech aTyr Pharma (NASDAQ: LIFE), who brought itolizumab to Steel’s attention.
“Bruce [Steel] said, ‘Do you think [Biocon] would be interested, if we started a company, to turn it over and make it available for us to develop here in North America?’” Bradbury said.
Biocon was amenable, and Equillium (initially called Attenuate Biopharmaceuticals) acquired the U.S. and Canadian rights to itolizumab, which is approved and marketed in India by Biocon as ALZUMAb as a treatment for moderate to severe plaque psoriasis, a skin condition. The drug is an outlier for Biocon, which is primarily a maker of biosimilars.
The deal with Biocon, India’s largest biopharma company, includes an exclusive supply agreement for clinical and commercial EQ001, which Biocon makes at commercial scale at an FDA-regulated facility. Biocon, which is not well known in the U.S., is the fourth largest maker of insulin worldwide.
After forming Equillium, the management team raised funds from friends and family. Later, the executives visited a number of crossover investors—companies that invest in both public and private entities—as they considered how best to raise funds to advance its programs.
Bradbury and his team soon realized they could move quickly to the public markets.
“The reality was that we were able to get the IND approved [to start clinical testing] in a very timely manner, we were very capital efficient in terms of what it took, so we still had plenty of capital,” Bradbury said. “We talked to a number of investment bankers, and basically had the opportunity take the company public and fully fund all the programs we had been planning to do.”
The management team’s experience at public companies also smoothed the path, he added. Jason Keyes, the company’s chief financial officer, worked with Bradbury at Amylin and held roles at other publicly traded businesses, as did Christine Zadelmayer, Equillium’s vice president of operations.
Today the company has 14 people, plus roughly double that number of people working remotely as long-term consultants. As of Sept. 30, it had recorded net losses of about $9.5 million since its inception in March 2017. The funding it had as of the end of 2018, about $66 million, is enough to keep the company operating for at least the next 24 months, according to a recent document filed with securities regulators.

Heat Biologics Interim Phase 2 Lung Cancer Data at ASCO-SITC

Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, today announced updated interim results from its ongoing Phase 2 study investigating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo�), in patients with advanced non-small cell lung cancer (NSCLC). The results were presented today at the ASCO-SITC Clinical Immuno-Oncology Symposium by Daniel Morgensztern, M.D., Associate Professor of Medicine and Director of Thoracic Oncology, Washington University School of Medicine, and Lead Investigator in the trial. Data were presented on both Cohort A and Cohort B of the trial. Cohort A enrolls only previously treated patients who have never received a checkpoint inhibitor (CPI), while Cohort B enrolls patients who received a minimum of 4 months of treatment with a CPI as part of their prior therapy, but subsequently had documented progressive disease.
“The treatment landscape for NSCLC has fundamentally changed as the number of patients who receive first line checkpoint inhibitor therapy is rapidly increasing,” said COL(ret) George E Peoples, MD, FACS, Heat’s Chief Medical Advisor. “The preliminary data from our Cohort B is increasingly relevant and potentially exciting as it suggests that the addition of HS-110 to nivolumab may restore anti-tumor activity in patients whose disease has progressed after treatment with a CPI.”
Jeff Hutchins, Ph.D., Chief Scientific and Operating Officer of Heat said, “The observed response rates and durability of disease stabilization support our mechanistic hypothesis that the broad, T-cell mediated immune response activated by HS-110 may improve patient survival when administered in combination with a CPI. The Cohort B data suggest that HS-110 may improve clinical outcomes for patients who have lost the benefit of treatment with a checkpoint inhibitor. We look forward to completing enrollment in this trial in Q2 and releasing additional results later this year as the data matures.”

MediciNova publishes findings on MN-166 in glioblastoma

MediciNova announced that Scientific Reports has published results from the animal model study evaluating MN-166, or ibudilast, in glioblastoma. The article, “Ibudilast sensitizes glioblastoma to temozolomide by targeting Macrophage Migration Inhibitory Factor,” is the first publication reporting the potential clinical utility of MN-166 for GBM. Key findings in this publication include the following: In an in-vitro study using patient derived cell lines, MN-166 combined with temozolomide showed significant synergism in cell cycle arrest and apoptosis, and In an in-vivo patient derived xenograft model study, combination treatment with MN-166 and TMZ resulted in significantly longer overall survival. Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc., commented, “We are very pleased that these findings were published in Scientific Reports. These findings compelled us to open an IND application and evaluate MN-166 in a clinical trial of patients with GBM. Enrollment is ongoing at Dana-Farber Cancer Institute.”

Acadia reports Q4 same facility revenue up 3.8% 

As part of its Q4 earnings, Acadia also reported Q4 patient days up 2.6% and revenue per patient up 1.2%.

Nuvectra price target lowered to $20 from $25 at Piper Jaffray

Piper Jaffray analyst Matt O’Brien lowered his price target on Nuvectra to $20 after its Q4 results, saying the new price target accounts for the divestiture of NeuroNexus and a modest push out of Virtis approval in his model. The analyst is also keeping his Overweight rating, noting that the company is headed for another year of increased share in the spinal cord stimulation market with expectations of adding another 15-20 reps to its sales force this year.

Rigel Pharmaceuticals’s Tavalisse seeing continued uptake, says Piper Jaffray

Piper Jaffray analyst Christopher Raymond kept his Overweight rating and $8 price target on Rigel Pharmaceuticals after Q4 results indicated “continued uptake of Tavalisse”. The analyst says the company is benefiting from the “improvements in physician awareness and an expanding sales force serving as growth levers that will continue into 2019.” Raymond adds that the pipeline efforts of Rigel Pharmaceuticals are on track with its Phase 3 wAIHA trial set to start in the first half of this year.

Hikma establishes partnership with Melinta in MENA

Hikma Pharmaceuticals PLC (Hikma, Group) (LSE: HIK) (NASDAQ Dubai: HIK)  (OTC: HKMPY) (rated Ba1 Moody’s / BB+ S&P, both stable) announces an exclusive license, supply and distribution agreement with Melinta Therapeutics  (Melinta), for Melinta’s intravenous and oral formulations of Baxdela™ (delafloxacin) across all its MENA markets. In addition, Hikma has the right of first negotiation for all other products in Melinta’s portfolio and pipeline in the region.
Baxdela™ is a novel antibiotic product used for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI). Baxdela™ is a fluoroquinolone with demonstrated efficacy against both gram-positive and gram-negative pathogens, including MRSA (methicillin-resistant Staphylococcus aureus). Baxdela™ was approved by the US Food and Drug Administration (FDA) in 2017.
Hikma is a leading provider of antibiotics in the MENA region, offering a wide range of products to doctors and pharmacists.  As Antimicrobial Resistance (AMR) continues to pose treatment challenges for healthcare professionals, offering this new, innovative product in the region will arm them with new ways to combat this growing threat.
Mazen Darwazah, Executive Vice Chairman and President of MENA said, “We are very pleased to establish a partnership with Melinta and to be able to bring this innovative product to the region.  As the challenge of AMR grows, we have an important role to play in helping to equip doctors here in MENA with the latest and most innovative developments.”

Mirati bulls will need patience

Hopes that Mirati could become the first company to succeed in targeting the “undruggable” KRAS oncology target have played a significant part in sending this company’s stock to an all-time high. But, judging by yesterday’s abstract drop for the upcoming AACR conference, the bulls will have to be patient. Both Mirati’s KRAS C12C inhibitor, MRTX1257, and Amgen’s rival AMG 510, will feature at the meeting, but there are no clinical data to report. Amgen’s three abstracts detail AMG 510’s discovery and in vivo characterisation, while Mirati has one preclinical abstract whose text has not yet been made available. Hopes were stoked by Amgen’s head of R&D, David Reese, who on an analyst call last month stated that the group was “seeing interesting early hints of clinical activity” and expected by mid-year to present “initial results … in terms of best-in-class”. These first results seem unlikely to come before Asco. MRTX1257 was Mirati’s early lead, but the current focus is on MRTX849, which has just entered phase I. Despite this early stage of development Leerink estimates that KRAS accounts for 70% of Mirati’s valuation, which today stands at a staggering $2.6bn.
ProjectCompanyMechanismStatusTrial ID
AMG 510AmgenKRAS G12C inhibitor1st in human data possible at AscoNCT03600883
TNO155NovartisSHP2 inhibitorStudy in KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mut tumoursNCT03114319
MRTX849Mirati (ex Array)KRAS G12C inhibitorTrial in KRAS G12C mut cancers started Jan 2019NCT03785249
KRAS TCRGilead (ex Kite/NCI)Anti-KRAS G12D engineered T-cell receptorNCI trial starting Mar 2019NCT03745326
UnnamedMiratiKRAS G12D inhibitorPreclinicalNone
MRTX1257MiratiKRAS G12C inhibitorEarly pipeline leadNone

Robotic pill seen safe in early human study, paving way for oral biologics

Transforming injectables into pills is hardly a novel idea, but a string of pharmaceutical/chemical efforts to evade the enzymes that break down the oral drug before it can be absorbed have largely hit a wall. Earlier this month, an animal study captured the spotlight for the potential of its blueberry sized robotic pill designed to deliver an insulin shot inside the stomach — but California-based Rani Therapeutics on Thursday said it has successfully tested its robotic pill for safety and tolerability in humans, paving the way for efficacy studies that could open the door to a colossal market to enhance treatment compliance, diminish the need for physician-led therapeutic administration and placate needle-phobic patients.

The company’s product — called the RaniPill — has undergone over 100 preclinical studies, including large animal trials. The capsule has an enteric coating that protects it from the acidic ambience of the stomach, and once it moves into the intestine and pH levels rise, the coating dissolves and a chemical reaction takes place which inflates a balloon. Pressure in the balloon pushes a dissolvable microneedle filled with the drug into the intestinal wall.
Intestines don’t have pain receptors, and the intestinal substrate — which is designed to absorb nutrients — is highly vascularized, making it the ideal location for the drug-engorged injection to deploy, Rani chief Mir Imran told Endpoints News, adding that in the handful of drugs the company tested as part of the RaniPill in animal studies, the absorption of the drug was generally equal or higher than that of a subcutaneous injection.
Following successful animal studies, Rani initiated a study in healthy humans last year to evaluate the feasibility of the product. Two groups of 10 subjects each (with one arm having fed, and the other arm having fasted) were given a drug-free version of the RaniPill. Results revealed neither group felt the impact of the capsule inflating or deploying, and each patient successfully expunged the remnants. The capsule was well tolerated and the presence (or absence) of food in the stomach had no impact on the performance of the capsule, the company said.
“This is the first time a robotic pill was swallowed by humans — this really paves the way for the next study which will have a drug, and we will be able to measure drug levels,” Imran said.
The company has chosen to use a pill loaded with octreotide, an off-patent biologic that treats the hormonal disorder acromegaly, for the upcoming study, which the company expects will commence in the coming months.
“If we’re successful in our next study, it really means that we can deliver any drug…including insulin and Humira and treatments for a whole host of other diseases such as multiple sclerosis, hemophilia and other chronic conditions,” he added.
But there’s a long road ahead. Each drug loaded into the capsule will require a separate study before Rani can petition the FDA for approval.
Meanwhile, rat and pig data on the other robotic pill — created by a team of researchers at MIT (including the prolific drug delivery maestro Robert Langer) and Novo Nordisk $NVO — announced earlier in February, has an alternative mechanism of action.
The device, called Soma, encapsulates a needle inside a pill made of compressed freeze-dried insulin that is designed to orient itself when it comes in contact with the stomach lining — inspired by a leopard tortoise, which brandishes a shell that allows the African reptile to right itself if it rolls onto its back. Upon contact with the wet inner lining of the stomach (which is also devoid of pain receptors), a sugar disk holding the needle in place is dissolved, making way for the needle to release its contents. The product is then engineered to disintegrate and travel harmlessly through the digestive system and eventually be eliminated, the researchers wrote in their report in Science.
“One big difference is that we predate the MIT effort by at least 5 years and our IP really covers everything they’re doing…their (Soma’s) spring loaded delivery is something we have very strong patents on, so I think they are going to step on our IP. The design of the needle we have very strong patents on, and their needle looks exactly like our needle,” Imran said, emphasizing the size of Rani’s patent portfolio, which he claimed includes 70 issued patents.
“The MIT group as far as we can tell has two patent applications and neither has been issued. Certainly for us we see that (competition) as a positive because it validates our approach in a very fundamental way — not that we need that validation thanks to our animal studies — but it’s really nice to have Bob Langer on my heels.”
In response to Imran’s commentary, Langer suggested it was unclear whether the MIT approach is infringing on Rani’s patents.

“I think it’s unclear at this time — recognizing that we, Rani, and I’m sure others have a number of patent applications in this area — whether, for some applications we are stepping on their patents, they are stepping on ours, and/or there are patents by others which will be important,” he said in an emailed statement.
“Our goal in publishing our work in a top peer reviewed scientific journal (Science) was to get the scientific principles we developed out to the scientific community in the hopes that it can get to patients. If that happens through us, our collaborators at Novo Nordisk, Rani, or someone else, we will have achieved our goal.”
Founded in 2012, Rani Therapeutics has raised $142 million in funding from a slate of investors including GV (the investment arm of Alphabet), and counts Novartis and Shire as its partners.

Another Phase 3 RSV fail hits Novavax, but execs claim there’s a way forward

Back in November 2016, when Novavax was picking up the scraps from a Phase III crash of its RSV vaccine in older adults, the company pointed to the Gates Foundation-backed program to test the vaccine in infants as a “significant commercial opportunity.” It went on to become the lead program as Novavax mounted an arduous comeback campaign for RSV-F vaccine.
But today, execs conceded that the infant trial has suffered the same late-stage fate.

Investors showed little patience for a company that’s been quick with explanations but slow to deliver. The stock $NVAX tanked more than 65% in pre-market trading to $2.13.
As it turned out, immunizing mothers with ResVax while they are pregnant did not prevent medically significant lower respiratory tract infections caused by RSV in infants for the first three months of their lives — the primary endpoint.
To be sure, Novavax is operating in a tough field littered with setbacks, including a flop from Regeneron (which has since dropped its RSV antibody). In a rare win, AstraZeneca recently secured expedited reviews in the US and EU for a different approach — a single dose long-acting drug for a broad swath of newborns.
What the treatment did achieve — and this is the silver lining that execs are holding onto as they try to beat down a path to approval — was protecting infants from “some of the most serious consequences of RSV, including RSV LRTI hospitalizations and RSV LRTI with severe hypoxemia,” CEO Stanley Erck said in a statement.
In other words, execs elaborated on a conference call, while the vaccine was not deemed effective for common — but less severe — manifestations of the respiratory syncytial virus, it appears to protect the small group of infants who get the worst attacks.
They also suggested that vaccinating mothers at an earlier stage of gestation (from 28 to 33 weeks) might increase efficacy — potentially a key point in their pitch to regulators.
Novavax offered a peek on the data, which it plans to unveil at a medical meeting. Respectively, the efficacy rates of ResVax in per-protocol infants were as follows:
39% against medically significant RSV LRTI (97.5%CI, -1% to 64%)
44% against RSV LRTI hospitalizations (95%CI, 20% to 62%)
48% against RSV LRTI with severe hypoxemia (95%CI, -8% to 75%)

Analysts Mixed After Fitbit’s Q4 Earnings

Fitness tracker and smartwatch maker Fitbit Inc FIT 13.96% swung back to a profit in the fourth quarter, but guidance for 2019 disappointed some investors.
The report was compelling enough for one research firm to turn bullish, but another continues to recommend investors stick to the sidelines for the time being.

The Analysts

D.A. Davidson’s Tom Forte upgraded Fitbit from Neutral to Buy with a 12- to 18-month price target lifted from $5.50 to $7.
Wedbush’s Michael Pachter maintains at Neutral, unchanged $6.50 price target.

D.A. Davidson: Healthier Company

Fitbit’s earnings report demonstrated the company is “much healthier” today than it has been in the past, Forte said in a research report. Some of the encouraging takeaways from the report include a return to unit and sales growth, sales coming in $11 million ahead of management’s own guidance and active user growth of 9 percent to 27 million.
Despite multiple encouraging takeaways, management did guide first-quarter sales, EPS and adjusted EBITDA short of the Street’s expectations. The company also guided its gross margins to be “much lower” than expected at 34.5 percent, but this is due to multiple temporary factors, including lower warranty benefit, a mix shift towards smartwatches and the migration to the cloud.
Forte said Fitbit’s focus on the health care market is still in the early stages but showing encouraging progress. Coupled with the multiple encouraging metrics seen in the fourth quarter and the $2.78 per share in net cash, the stock offers a favorable risk to reward profile at current levels.

Wedbush: Discouraging Guidance

Fitbit’s report exceeded expectations and shows the company controls a large portion of the fitness tracking and smartwatch markets, Pachter said in a research report. Guidance for 2019 is “somewhat discouraging” as it implies only modest revenue growth, gross margin contraction and earnings losses.
Nevertheless, Pachter said Fitbit is adopting a strategy of pushing hardware sales and then leverage its user-base and technologies to gain traction in health care products and services. The company’s Fitbit Health Solutions (FHS) business has significant long-term potential, but management’s hasn’t fully explained the true opportunity.
Before potentially turning more constructive on the stock, investors may want to wait for signs of a quicker growth trajectory and more transparency, especially within the FHS business

Analysts Laud Sarepta’s ‘Increasingly Active’ Gene Therapy Development

Sarepta Therapeutics Inc SRPT 4.94% reported fourth-quarter results Wednesday alongside positive results for its muscular dystrophy gene therapy candidate.

The Analysts

Janney analyst Yun Zhong reiterated a Buy rating on Sarepta with a $200 fair value estimate.
Cantor Fitzgerald analyst Alethia Young reiterated an Overweight rating and increased the price target from $217 to $231.

Janney: Strong Balance Sheet Needed For Active Clinical Program

Sarepta continues to move ahead with its gene therapy and exon-skipping pipelines, Zhong said in a Thursday note.
The company will initiate a multicenter registrational study of microdystrophin gene therapy using commercial-scale material by the end of 2019, the analyst said.
Sarepta is seeking to discuss a regulatory pathway for all five limb-girdle muscular dystrophy, or LGMD, gene therapy programs with the FDA, Zhong said.
Janney projects that Sarepta will more than double the exon-skipping market in 2020, given the scheduling of the golodirsen PDUFA date for August and the potential for a midyear NDA submission for casimersen.
Reviewing the results, Janney attributed Sarepta’s fourth-quarter loss to upfront and milestone payments due to gene therapy partners Lysogene and Myonexus.
Even as the company forecast an increase in operating expenses due to gene therapy manufacturing, Zhong said a strengthened balance sheet should support its “increasingly active” clinical development.

Cantor Sees Compelling LGMD Opportunity

The limb girdle data released Wednesday exceeded expectations, Young said in a Thursday note. The analyst views the collective LGMD opportunity as a compelling one, with a target population similar to DMD, with over 10,000 patients in the U.S.
The analyst said she hopes to get further updates on LGMD development strategy later this year following regulatory interactions. The Paragon commercial manufacturing facility is expected to be ready by the first quarter of 2020, Young said.
“We have raised our probability of success for MYO-101, ‘103 and ‘201 to 50 percent from 25 percent and left MYO-102 and ‘301 programs unchanged.”
Cantor sees meaningful read-through across these programs because they use a similar approach.

FDA: Regulatory Process For CBD Edibles Kicks Off With April Hearings

Food and Drug Administration Commissioner Scott Gottlieb said his agency has plans to regulate CBD edibles and will start holding public hearings on the matter as early as April.

What Happened

The FDA has taken notice of the legalization of hemp and CBD in December, Gottlieb said during a Wednesday House Appropriations Committee committee.
The agency is assembling a team of senior officials to develop new rules and will start the process with a public hearing in April.
Gottlieb also warned the committee that the regulations concerning CBD-infused food products will not be straightforward. As a potential pathway, Gottlieb said the FDA might regulate products with high CBD content as drugs and subject them to more stringent rules, but products with lower concentrations could be categorized as food products.

Why It’s Important

Since the legalization of hemp and hemp-derived CBD in the Farm Bill, the CBD industry has eyed the FDA’s position toward the substance, as it represents an obstacle to mass-market CBD edibles from a federal standpoint.
A clear set of rules would make it easier for companies like New Age Beverages Corp NBEV 4.65% to distribute their products and would eliminate the uncertainties that might prevent large retailers such as Walmart, Inc. WMT 0.87%, from offering CBD products.

Adial CEO: Medical Solution For Alcoholism Could Be Just Around Corner

More than 15 million Americans suffer from alcohol use disorder, according to the CDC, but a new medication may offer a solution. Adial Pharmaceuticals Inc ADIL 1.39% is developing AD04, a drug in Phase IIb clinical trials for treatment of alcohol addiction.

Precision Medicine

This week, Adial CEO Bill Stilley discussed the prospects for AD04 in an interview with CBS San Francisco affiliate KPIX-TV. AD04 is genetically targeted to help a specific subset of people suffering from alcohol addiction due to genetic factors, he said.
“We believe that this drug can help those patients,” the CEO said. “But in the future, as we start to understand more about the brain, more about addiction, we’ll be able to develop other drugs and other people will develop other drugs to help a different segment of the population.”
Adial’s approach to complex psychological conditions such as addiction and depression is known as precision medicine, and it was facilitated by the unlocking of the human genome at the beginning of the 21st century, Stilley said.
“I think it’s the wave of the future. It’s how all drugs will be targeted.”

Universal Treatments

Like depression and other conditions, the causes and types of alcohol addiction vary from person to person, and one universal treatment is unlikely to help every patient, Stilley said, adding that AD04 showed promising results in its Phase IIb trials.
“Patients has a significant reduction in how often they drank, and then, importantly, when they drank, a 60-percent reduction in the amount they drank.”
AD04 works by modifying the dopamine system in the brain that is involved in cravings.

Major Problem

Alcohol-impaired driving is a factor in more than 30 percent of fatal traffic accidents each year, according to the CDC. Each year, more than 88,000 Americans die as a result of alcohol abuse.
“It is one of the single worst diseases in the world and in the United States,” Stilley said.

Martha Stewart is getting into the marijuana business

Martha Stewart is moving from pots and pans to pot.
The housewares goddess announced Thursday that she’s partnering with marijuana grower Canopy Growth for a new line of CBD-based products for humans and animals.
“I am delighted to establish this partnership with Canopy Growth and share with them the knowledge I have gained after years of experience in the subject of living,” Stewart said in a statement.
“I’m especially looking forward to our first collaboration together, which will offer sensible products for people’s beloved pets.”
Canopy Growth Chairman and co-CEO Bruce Linton sang Stewart’s praises.
“As soon as you hear the name Martha, you know exactly who we’re talking about,” Linton said in a statement. “Martha is one of a kind and I am so excited to be able to work alongside this icon to sharpen our CBD product offerings across categories from human to animal.”
Stewart will also serve as an adviser for the company, which is one of Canada’s major producers.
In 2016, Snoop Dogg, who co-hosts “Martha & Snoop’s Potluck Dinner Party” with Stewart, partnered with Tweed, an Ontario-based subsidiary of Canopy Growth.
So far, the rapper and Tweed have launched three strands under his “Leafs by Snoop” brand: “Sunset,” “Ocean View” and “Palm Tree.”

Allergan holder Chevedden backs Appaloosa plan to split CEO-chair roles

Appaloosa LP said on Thursday investor John Chevedden was backing the hedge fund’s proposal to split the roles of chairman and chief executive officer at Botox-maker Allergan Plc.

Chevedden, an activist investor who frequently files shareholder rights proposals, had withdrawn his own proposal for Allergan and would support Appaloosa’s, the hedge fund said, adding that this would eliminate unnecessary confusion.
“John Chevedden has worked tirelessly for many years to advance important corporate governance initiatives and we are gratified that he shares our view,” said Appaloosa President David Tepper.
Earlier this month, Tepper stepped up pressure on the botox maker to consider selling itself and splitting the top roles immediately, if management is unable to turn around recent lagging performance.
In response, the drugmaker said implementing Appaloosa’s recommendations would be “highly disruptive” to Allergan’s operations and on Thursday redirected Reuters to its earlier response when asked to comment.
Allergan’s shares, which fell 18.3 pct in 2018, have been lagging those of its peers on account of dropped plans to sell its women’s health unit, a disappointing revenue outlook for 2019 and increasing competition for many of its important drugs.
The company’s fourth-quarter sales fell 5.7 percent, while sales of its second-most important drug, Restasis, fell 17.7 percent.

Marijuana well tolerated among elderly patients; nearly a third reduced opioids

Medical cannabis was well-tolerated among elderly patients and provided significant symptomatic benefits, a retrospective chart review showed.
Adults who were an average age of 81 experienced relief in chronic pain, sleep, neuropathy, and anxiety with medical cannabis, reported Laszlo Mechtler, MD, of Dent Neurologic Institute in Buffalo, New York, and colleagues, in an early-release abstract from the American Academy of Neurology meeting to be held here in May.
Moreover, 32% reduced their opioid pain medication, they added.
At first, about a third of patients experienced adverse effects — mostly sleepiness, balance problems, and gastrointestinal disturbances — but in 13% of patients, those problems resolved when dosages were adjusted.
Similar findings were seen last year in a study published in the European Journal of Internal Medicine, in which elderly patients reported significantly less pain with medical cannabis and more than 18% stopped or reduced opioid analgesics.
In the U.S., people age 65 and older are among the fastest-growing group of cannabis users. To date, 33 states and the District of Columbia have legalized medical marijuana. Ten states also have legalized recreational use, and that’s caused some experts to be concerned about older adults who may self-treat medical problems without guidance.
“Evidence is growing in support of some indications for medical cannabis — pain, for example — and that needs to be weighed against side effects to which older adults may be more vulnerable, like dizziness, somnolence, confusion, and dry mouth,” Joshua Briscoe, MD, of Duke University Medical Center, told MedPage Today. “Older adults should use caution when experimenting with medical cannabis on their own and share the details of such use with their physicians.”
In this study, Mechtler and colleagues analyzed charts of 204 patients from ages 75 to 102 years who used the New York state’s Medical Marijuana Program. They had an average age of 81 and were followed in a neurologic outpatient setting in Buffalo. Of the total sample, 129 were women and 75 were men.
Participants took various ratios of tetrahydrocannabinol (THC) to cannabidiol (CBD) by mouth as a liquid extract tincture, capsule, or in an electronic vaporizer, for an average of 16.8 weeks.
Initially, 34% of participants experienced adverse effects; after adjusting dosages, that figure dropped to 21%. The most common side effects were sleepiness (13%), balance problems (7%), and gastrointestinal disturbances (7%). Due to side effects, seven patients (3.4%) stopped using medical marijuana. The most common ratio of THC to CBD among people who reported no side effects was 1:1.
Overall, 69% of participants experienced symptom relief, largely improvements in pain (49%), sleep (18%), neuropathy (15%), and anxiety (10%).
“With legalization in many states, medical marijuana has become a popular treatment option among people with chronic diseases and disorders, yet there is limited research, especially in older people,” Mechtler said in a statement.
“Our findings are promising and can help fuel further research into medical marijuana as an additional option for this group of people who often have chronic conditions,” he added. “Future research should focus on symptoms like sleepiness and balance problems, as well as efficacy and optimal dosing.”
The study was supported by the Dent Family Foundation.

Acceleron treatment of Charcot-Marie-Tooth disease gets FDA orphan tag

In a post on the FDA’s website, Acceleron’s treatment of Charcot-Marie-Tooth disease, efmitermant alfa, received FDA orphan designation.

Denali expands antibody discovery deal with AbCellera

Denali Therapeutics has expanded its antibody discovery deal with AbCellera. The agreement tasks AbCellera with generating panels of antibodies for up to eight targets picked by Denali.
AbCellera wrapped up the first phase of its collaboration with Denali last year. That collaboration saw AbCellera search immune responses for naturally derived antibodies with specific binding properties against a neurodegenerative disease target of interest to Denali.
With antibodies discovered by AbCellera now in Denali’s preclinical pipeline, the neurodegenerative disease specialist has firsthand experience of the merits of its partner’s platform and the antibodies it yields. That experience led to the new deal.
“We continue to be impressed with the speed of discovery, the quality and the diversity of the antibodies AbCellera delivers,” Denali COO Alexander Schuth said in a statement.
In expanding the agreement, Denali has secured a source of antibodies against up to eight targets. Denali is paying a technology access fee and funding research, while committing to milestones and royalties, to secure the expanded relationship with AbCellera.

The expansion of the deal comes weeks after AbCellera struck a 10-target deal with Novartis. Talking at the time, AbCellera CEO Carl Hansen framed the Novartis agreement as an inflection point for his antibody R&D shop. Having made its name through single-target deals with GlaxoSmithKline, Merck and Teva, Hansen saw Novartis as the start of AbCellera’s move into “extended access” agreements.
Landing the eight-target Denali deal adds weight to the view that AbCellera is at an inflection point. To support its growing workload, AbCellera moved into a 22,000-square-foot lab last year and plans to grow its headcount from 72 to around 100 by the end of 2019.
For Denali, the AbCellera deal provides it with a source of antibodies as it seeks to stock its pipeline with neurodegenerative disease prospects. Denali’s lead drugs are now in the clinic but it also has a clutch of early-stage programs coming down the pipe.

Bispecifics player Abpro teams with China’s NJCTTQ in deal worth up to $4B

Abpro is partnering with China-based NJCTTQ to develop new bispecific antibodies using its antibody discovery platform. Under the agreement, Abpro could collect up to $4 billion, which includes $60 million in “near-term R&D funding,” as well as milestone payments and royalties.
Abpro will hold on to the rights for any drugs approved outside of China and Thailand, and NJCTTQ will retain the rights in China, Abpro said in a statement. The pair will use Abpro’s DiversImmune technology, one of two platforms the Massachusetts-based company uses to develop drug candidates. The company was vague about the targets of the collaboration, saying only that they would develop bispecific antibodies, such as T-cell engagers, for immuno-oncology.
“This collaboration further validates our platform’s unique ability to develop best-in-class bispecific T-cell engagers, with significant potential to treat patients living with cancer,” said Ian Chan, Abpro’s co-founder and executive chairman, in the statement. “NJCTTQ has substantial clinical development and commercialization expertise that is highly complementary to our immuno-oncology development platforms as we focus on broadening our pipeline and expanding our ability to treat more patients globally.”
“We intend to pursue additional similar development collaborations that leverage our innovative technology platforms and programs that include commercial rights in key global markets,” Chan added.
This isn’t the first time Abpro has tied up with a Chinese company. In 2016, Abpro signed a $3.5 million deal with Chinese biotech Essex Bio to co-develop monoclonal antibodies. Essex Bio, which specializes in recombinant DNA technology, would retain commercial rights in China, while Abpro would hold them for the rest of the world.
Abpro filed to raise up to $86 million in an IPO last April, hoping the proceeds would fund clinical trials of its lead antibodies for cancer and vascular eye disease in 2019. However, a month later, it put off the IPO, delaying a capital infusion it hoped would support the first clinical trials of those programs.

Third Akorn sterile drug plant hit by FDA as new CEO lays out future blueprint

Akorn Pharmaceuticals, which had a $4.3 billion buyout by Fresenius tank last fall, just can’t seem to catch a break.
Just weeks after being hit with an FDA warning letter for its manufacturing operations in Illinois—problems that led to the death of the deal—Akorn today reported that it has received a citation on its third U.S. facility While the four observations were relatively minor, it was a downer on the same day the new CEO Douglas Boothe was telling the market Akorn is ready to move past its regulatory challenges and buyout debacle with Fresenius.
“Our recent financial results reflect the many challenges that have impacted our business of late, including increased competition for many of our generic and promoted products, supply issues, and regulatory and legal challenges,” Boothe said in a statement as the company reported fourth-quarter earnings. “Despite these significant headwinds, we have strong fundamentals to build upon … I look forward to providing updates in the coming months on our go-forward strategy and plan to rebuild value for all of our stakeholders.”
Akorn Thursday reported a 17.6% drop in revenues to $153.4 million for the fourth quarter, attributed in large part to supply shortfalls after the company halted manufacturing to deal with FDA concerns at its Decatur and Somerset, New Jersey  manufacturing facilities. It reported an adjusted net loss to of $0.29 per diluted share, double the loss of $0.14 per diluted share in the same quarter of 2017.
The new Form 483 for Akorn’s sterile drug manufacturing operation in Amityville, New York, was noted in an SEC 8K filing the drugmaker made Thursday. It lists four observations including for a record keeping misstep and failing to do stability testing on time.
It was minor compared to the issues outlined in a 22-page Form 483 for its Decatur, Illinois, plant which preceded a warning letter this year. In that the FDA raised questions about data integrity at the plant, repeat testing of failed batches and other issues that could lead to sterile drug contamination.
Boothe is working to move the company past the failing that doomed the deal with Fresenius. He said in his two months with Akorn, the company has made structural and organizational changes to “emphasize compliance, transparency, and accountability,” at its three U.S. manufacturing facilities. On top of that,  Akorn has decided to “explore strategic alternatives” to divest its India manufacturing facility, the CEO said.
Germany’s Fresenius struck its $4.3 billion buyout offer in 2017, touting the acquisition as a “strategically complementary combination” that would diversify its portfolio and expand its Fresenius Kabi sterile manufacturing capacity. But the deal fell apart last year after Fresenius got tipped off that Akorn violated FDA drug-development standards.
Akorn sued to try to force the deal on Fresenius, but a Delaware judge ruled that the German company was legally entitled to dump the deal. Days later, then-Akorn CEO Raj Rai stepped down.