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Wednesday, August 10, 2022

Aridis Pan-Coronavirus, Inhaled Antibody Cocktail Protective in Non-Human Primates

  Aridis Pharmaceuticals, Inc. (Nasdaq: ARDS), a biopharmaceutical company focused on the discovery and development of novel anti-infective therapies to treat life-threatening infections, announced today that inhaled treatment of its fully human monoclonal antibody cocktail AR-701 resulted in no detectable SARS-CoV-2 virus in the lungs of infected rhesus macaques, and protected their lungs from disease. AR-701 was effective in the non-human primates when used either as a prophylactic or therapeutic treatment regimen.

  • Therapeutic administration of inhaled AR-701 substantially reduced and continued to suppress the viral load in the nasal sinus and oropharynx (upper respiratory tract region) for the entire 5-day testing period.
  • Additional lab research also indicates both mAbs in the AR-701 cocktail are effective against the SARS-CoV-2 Omicron BA.1, BA.2, BA.4, BA.5 subvariants in vitro

This non-human primate research was conducted through a collective effort involving researchers at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU), the University of California at DavisVanderbilt University, the University of California at Irvine, and Aridis, with a grant supplement to OHSU from the National Institutes of Health's Office of Research Infrastructure Programs in the Office of the Director (OD, PHS grant P51 OD011092).  Preliminary study results were recently presented at the Immunotherapy for Infectious Diseases Conference 2022 in Pavia, Italy. Additional data are being analyzed and will be submitted to a peer-reviewed scientific journal for publication.

https://www.biospace.com/article/releases/aridis-pan-coronavirus-inhaled-monoclonal-antibody-cocktail-ar-701-is-protective-in-non-human-primates/

Billions in Debt and Buried in Opioid Lawsuits, Endo Eyes Bankruptcy

 Shares of Endo International plunged nearly 40% Tuesday after the company disclosed the imminence of filing for Chapter 11 bankruptcy due to its debt load and the thousands of opioid lawsuits the drugmaker is facing across the United States.

In its quarterly earnings report released Tuesday, Ireland-based Endo posted a 20% decrease in revenue for the three-month reporting period. The company earned $569 million in the second quarter of 2022, down significantly from the $714 million it posted in Q2 2021. Earnings fell in part due to the loss of exclusivity for one of Endo’s key drugs, Vasostrict, which is used to increase blood pressure in adults with vasodilatory shock.

The company noted an uptick in revenue for Xiaflex, which is intended for the treatment of Dupuytren's contracture and Peyronie's disease. Xiaflex generated $121 million during the quarter, up from $111 million the previous year. Overall, revenues from Endo’s branded pharmaceuticals fell 4% during the quarter.

Endo noted it carried approximately $8.1 billion in debt and had about $1.2 billion in unrestricted cash. In its announcement, the company said it “remains in constructive negotiations” with a group of first lien creditors. These negotiations will likely result in filing for Chapter 11 in the U.S. Bankruptcy Court, the company said. Endo also noted that it remains in discussion with opioid-related litigants but did not provide information regarding possible settlements.

Buried in Opioid Lawsuits

Like other opioid companies, Endo has been embroiled in thousands of lawsuits brought by state and local governments charging it, as well as other opioid makers, with aggressive marketing tactics that spurred the opioid epidemic. However, unlike other opioid drugmakers such as Purdue, which previously filed for bankruptcy, Endo has not secured a comprehensive agreement with the thousands of opioid plaintiffs, which leaves the company potentially open to billions of dollars in legal liability.

According to the Wall Street Journal, Endo has struck a few agreements with plaintiffs in Florida, Texas, New York, West Virginia and Alabama. However, the company continues to face more than 3,500 lawsuits from other government entities, the Journal said.

In 2017, at the request of the U.S. Food and Drug Administration, Endo removed its reformulated opioid pain medication Opana ER from the market. As BioSpace reported at the time, Opana ER was initially approved in 2006 for the management of moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.

In 2012, the company changed the formulation of Opana ER to make it more resistant to potential abuse. Although the FDA said the reformulation met its standards, the data did not show the new formula could be expected to “meaningfully reduce abuse” of those who wanted to snort or inject the drug. While it was more difficult to crush and snort, Opana ER was still able to be injected, and the abuse continued. The abuse of Opana ER was linked to an outbreak of HIV in rural Indiana due to opioid abusers sharing needles.

If Endo files for Chapter 11, that will provide the company with some protection from ongoing lawsuits. The Journal said Endo’s creditors will likely be paid first before any lawsuits would be paid out under potential bankruptcy. However, the Journal also speculated that before Endo, which has U.S. operations based in Malvern, Pennsylvania, can file for bankruptcy, it will likely need to reach an agreement with the bulk of the plaintiffs before the courts will sign off on a reorganization.

Recent Opioid Agreements  

While Endo struggles with its financial and legal burdens, other companies involved in the thousands of opioid-related lawsuits have been moving to strike deals and mitigate further losses. Purdue Pharmaceuticals, which was the poster child of sorts for opioid abuse, reached an agreement with plaintiffs that will allow it to move forward with its reorganization plan and rebrand to Knoa Pharma. A majority of the new company’s profits will be used to abate the ongoing crisis.

Teva Pharmaceuticals and Johnson & Johnson have also been embroiled in multiple opioid-related lawsuits. Some cases have been settled, while others remain open. Earlier this year, a national settlement was reached with three of the biggest distributing companies, Amerisource Bergen, Cardinal Health and McKesson. Under the terms of that deal, the three companies will pay up to $19.5 billion to settle claims.

https://www.biospace.com/article/billions-in-debt-and-buried-in-opioid-lawsuits-endo-eyes-bankruptcy/

Langya Virus Outbreak Sounds Alarm as Monkeypox, COVID-19 Continue to Spread

 A study recently described how climate change is making more than half of hundreds of known infectious diseases worse, monkeypox is spreading and on Tuesday, news broke of a Langya henipavirus outbreak in China.   

Although COVID-19 is not likely to be eradicated, and the pandemic itself is not over, researchers and public health officials are turning an eye toward the future, trying to get a bead on what might cause the next pandemic

The focus is largely on zoonotic viruses, such as SARS-CoV-2, the virus that causes COVID-19. Zoonotic viruses originate in animals and make the jump, through contact or mutations, to humans. Examples include the Ebola, Zika and West Nile viruses. An April study published in Nature noted there are approximately 10,000 viruses with the potential to infect humans, and most are “circulating silently in wild mammals.” Climate change and changes in land-use patterns increase the likelihood of cross-species viral transmission.

Coronaviruses, Filoviruses and Flaviviruses

Researchers are looking closely at three broad types of viruses. The first is coronaviruses. These include SARS-CoV-2 as well as the viruses responsible for SARS and MERS. The latter two jumped from animals to humans, and it’s likely that SARS-CoV-2 did as well. Coronaviruses cause mild to moderate upper-respiratory tract diseases in humans, typically, but as we know from COVID-19, SARS and MERS, they can be deadly.

The second is Ebola, which is a member of the family filoviruses. Also a zoonotic disease, Ebola likely transferred from bats or monkeys to humans. It causes hemorrhagic fevers – leading to serious internal bleeding that can be deadly. Another member of this class is Marburg virus.

The third is mosquito-borne viruses, primarily flaviviruses. These are also transmitted by ticks. They include diseases like West Nile, dengue and yellow fever. They don’t spread from person to person, which limits the likelihood of a pandemic. They only spread as far as mosquitos travel, which, unfortunately, is expanding as the climate warms.

Langya Virus Triggers Alarm Bells

Approximately 35 people in China have been diagnosed with a newly identified virus, which is being dubbed Langya henipavirus (LayV). It comes from the same family as the Nipah and Hendra viruses, which can be deadly. LayV was identified due to an early detection system for people with fevers with a recent history of animal exposures in eastern China. The patients were primarily farmers, reporting fatigue, cough, loss of appetite and body aches. Several also developed abnormal blood cells and liver and kidney damage. All survived.

The virus does not appear to be transmitted from person to person. It seems to have been spread by shrews, a small type of rodent, which are a known vector for similar henipaviruses. The virus has also been identified in some goats and dogs. Testing of 25 wild animal species suggested the shrew was a natural reservoir for the virus, with it being identified in 27% of shrews tested (compared to 2% of goats and 5% of dogs).

FDA Expands Authorization for Monkeypox Vaccine

Experts say monkeypox is very unlikely to become pandemic, even though there is currently an outbreak. The first recorded human infection of monkeypox was in the Democratic Republic of Congo in 1970. It has only been documented outside of Africa six times. There have been about 9,000 reported cases in the U.S. to date, across 49 states, Washington, D.C. and Puerto Rico, according to the Centers for Disease Control and Prevention. No deaths have been reported in the U.S. from monkeypox.

Symptoms are similar to smallpox – which was eradicated globally in the 1970s – but are milder. Initial symptoms are similar to the flu, with fever, chills, headache, exhaustion and muscle pain. Monkeypox causes swelling of lymph nodes while smallpox does not. It is also marked by a severe rash. It generally lasts two to four weeks and can be fatal. Some reports suggest up to 10% of monkeypox patients die from the disease. It is primarily spread via skin-to-skin contact during sex. It can be spread by close physical contact, including hugging and kissing, and through contaminated bedsheets or other bedding. Currently, gay and bisexual men are considered to be at the highest risk.

There is a vaccine, which is basically the smallpox vaccine. On Tuesday, The U.S. Food and Drug Administration expanded authorization for the monkeypox vaccine in a way that will increase its availability. While it is traditionally administered via subcutaneous injection, the new authorization allows healthcare providers to give the shots to adults through intradermal injection, between the layers of the skin, which will require one-fifth of the dose. This will expand the 400,000 vials in the strategic national stockpile to about 2 million shots.

Children will still receive the shots subcutaneously as public health officials don’t have enough data on whether intradermal injections work for children. The vaccine, Jynneos, is the only FDA-approved monkeypox vaccine in the U.S. It is administered in two doses 28 days apart. It is manufactured by Danish company Bavarian Nordic.

COVID-19: Introducing BA.4.6

As of August 9, there were 1,021, 898 new cases of COVID-19. In the U.S. alone, on the same date, there were 128,676 new cases. For the most part, access to effective vaccines and booster shots, and the availability of treatments such as Gilead’s Veklury, Merck’s molnupiravir and Pfizer’s Paxlovid, as well as some of the antibody treatments, have made the disease manageable, although it can still be potentially deadly in the unvaccinated, elderly and immunosuppressed.

As we know now, SARS-CoV-2 mutates fairly easily and rapidly. Currently, the spread is by the Omicron BA.4 and BA.4 subvariants, which are extremely contagious, demonstrate some evasion from immunity caused by vaccines and previous infections but are potentially less deadly. That doesn’t mean future mutations won’t be even more deadly and even more infectious.

There is also now evidence of yet another Omicron variant, BA.4.6.

“We’ve seen a pretty rapid increase in the number of BA.4 and BA.5s and the expected increase in the number of samples we can sequence,” Bailey Glen, Ph.D., an assistant professor in the College of Medicine at the Medical University of South Carolina (MUSC) said. “And there’s definitely some subtype information that may be relevant. We see a BA.4.6 that we haven’t seen until now. There’s still lots of change going on. From a genetic perspective, it’s still rapidly adapting. It's still just kind of wild how much it’s able to change and adapt.”

It's still unknown if this subvariant will have any impact or staying power.

Julie Hirschhorn, Ph.D., director of the molecular pathology lab at MUSC, said, “I think that we’re surging again. We’re either heading into it or in it. It’s a little hard to tell because there’s not as much reporting of positive tests as before to make it as clear what’s going on. But it does appear that we’re surging again. It’ll be interesting to see how long this wave lasts.”

Bivalent vaccines that target the original Wuhan wildtype strain and Omicron are expected to roll out this fall, but it’s too early to know whether they will be effective against BA.4.6, should it continue to spread.

https://www.biospace.com/article/langya-virus-outbreak-sounds-alarm-bells-as-monkeypox-covid-19-continue-to-spread-/

BMS Bets up to $1.9 Billion on GentiBio’s Treg Platform for IBD

 Within the next eight years, more than 3.5 million people in the United States are expected to be diagnosed with inflammatory bowel disease. With those rising numbers in mind, Bristol Myers Squibb is doubling down on treating the condition with a nearly $2 billion partnership with GentiBio to develop Treg therapies for patients with IBD.

Inflammatory bowel disease is an umbrella term for two difficult-to-treat diseases: Crohn’s disease and ulcerative colitis. Both Crohn’s and UC are characterized by chronic inflammation of the gastrointestinal (GI) tract. That inflammation ultimately damages the patient’s GI tract, which spans from the mouth to the anus.

The exact cause of inflammatory bowel disease is not entirely understood. However, it is believed to involve an interaction between the immune system, genes and environmental factors.

Pharma giant Bristol Myers Squibb, which won regulatory approval for ulcerative colitis drug Zeposia, is turning to cell therapy for potential long-lasting treatment of these diseases. In partnership with Boston-based GentiBio, BMS aims to harness the capabilities of engineered Treg therapies to re-establish immune tolerance and repair tissue in patients living with IBD. 

A Potential Functional Cure 

Regulatory T cells, otherwise known as Tregs, are a specialized type of T cell that can modulate both the innate and adaptive immune systems and suppress immune responses that can lead to inflammation that plays a significant role in IBD. BMS and GentiBio hope the use of Tregs will provide lasting support to patients, particularly those that have not achieved improvement from available small molecules and biologics. 

Many of the current therapies aimed at types of IBD, including AbbVie’s Humira, the world’s top-selling drug, can have adverse effects outside the GI tract. They can also suppress the body’s ability to effectively respond to infections and diseases, such as COVID-19. GentiBio’s approach aims to mitigate those concerns about immune suppression. Tregs are designed to suppress multiple inflammation mechanisms and promote homeostasis within the tissue to stimulate the body’s self-repair capabilities.

GentiBio launched last year with a technology platform aimed at combining Tregs biology and antigen receptor engineering in order to develop engineered Tregs designed to provide a functional cure for autoimmune and autoinflammatory diseases. Adel Nada, co-founder and CEO of GentiBio, told BioSpace that the Tregs developed by his company can suppress inflammation in the targeted area while also repairing tissues damaged by excessive inflammation. 

For IBDs, this includes repair to the mucosal lining of the intestines. By repairing that lining, Nada explained that the healing property of the Tregs will prevent the incursion of the microbiome of the intestine into the gut, which can be detrimental to patients. 

“By repairing the gut/ microbiome interface… we believe we have the potential to reverse the pathology of IBD and reestablish tolerance within the body,” Nada said. “Unlike existing therapies, Tregs have the unique potential to re-establish immune tolerance in autoimmune and inflammatory diseases such as IBD." 

Nada said Tregs, which have been in development by other companies for autoimmune and inflammatory diseases, have been aimed at IBD before. However, he noted that many of those first-generation Treg-based therapeutics did not achieve the desired levels of safety and efficacy that developers had hoped for.

“It’s a challenging disease to begin with,” he said, noting the lack of success with those early Treg approaches.

As IBDs become more commonplace, Nada said they will have more opportunities to determine the best approach to treating the diseases with this modality. As the treatments improve, Nada said the manufacturing process will improve, which should help maintain cost efficiency. 

A Validation of the Treg Space 

Under the terms of the multi-year collaboration, GentiBio will apply its modular engineered Treg platform and scalable manufacturing process to produce stable and disease-specific engineered Tregs against multiple targets. What those targets are have not been disclosed. BMS will be eligible to develop and advance up to three of the programs from the collaboration into clinical trials.

Robert Plenge, senior vice president and head of translational medicine at BMS and head of the company’s immunology, cardiovascular and fibrosis thematic research center, touted the potential of Tregs for IBD. In other disease-based spaces, Plenge said Tregs have “demonstrated the potential to suppress inflammation and autoimmune dysfunction in a tissue-restricted manner,” which had led to the avoidance of harmful immune suppression. Plenge added that the companies will look to the promise of Tregs and explore their potential in IBD. 

Nada said he not only views the collaboration with BMS as an important validation of GentiBIo’s Treg platform and approach, but he believes it will also be a validation of the Treg space “writ large.”

The partnership's financial terms include an undisclosed cash payment made to GentiBio. As the program unfolds, GentiBio stands to make up to $1.9 billion in development and commercial milestone payments, as well as royalties on any approved therapeutics. 

https://www.biospace.com/article/bms-bets-up-to-1-9-billion-on-gentibio-s-treg-approach-to-treating-ibd/

Amazon Receives FDA Warning Letter For OTC Mole Removal Products

 

  • The FDA's Center for Drug Evaluation and Research released a warning letter sent to Amazon Inc's (NASDAQ: AMZN) CEO Andy Jassy for selling mole removal products over-the-counter.

  • The letter explains that the company is responsible for "introducing, delivering, or causing the introduction or delivery into interstate commerce of products that are unapproved new drugs."

  • "There are no over-the-counter (OTC) drugs that can be legally sold for mole or skin tag removal, and FDA has safety concerns about drugs marketed OTC directly to consumers for these uses," the agency said.

  • The FDA noted that its concerns are reflected in the OTC final monograph for wart remover drug products (now a final administrative order under section 505G of the FD&C Act), "which specifically warns against the use of OTC topical wart remover products on moles and birthmarks."

  • FDA said it specifically purchased two mole and skin tag remover products via Amazon, "Deisana Skin Tag Remover, Mole Remover, and Repair Gel Set" and "Skincell Mole Skin Tag Corrector Serum," which were delivered by Amazon.

  • Amazon has 15 days to respond, with the FDA adding, "If you believe that the products you distribute are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration."

  • In an emailed statement to Benzinga, Amazon's Spokesperson said “Safety is a top priority at Amazon. We require all products offered in our store to comply with applicable laws and regulations. The products in question have been investigated and removed.”

Bristol Myers, 2seventy Topline Results Succeed in Multiple Myeloma Study

 Bristol Myers Squibb (NYSE: BMY) and 2seventy bio, Inc. (Nasdaq: TSVT) today announced positive topline results from KarMMa-3, a Phase 3, global, randomized, multicenter, open-label study evaluating Abecma (idecabtagene vicleucel) compared to standard combination regimens in adults with multiple myeloma that is relapsed and refractory after two to four prior lines of therapy and refractory to the last regimen. KarMMa-3 is the first randomized clinical trial to evaluate a CAR T cell therapy in multiple myeloma. Results of a pre-specified interim analysis conducted through an independent review committee showed that KarMMa-3 met its primary endpoint of demonstrating a statistically significant improvement in progression-free survival. Treatment with Abecma also showed an improvement in the key secondary endpoint of overall response rate compared to standard regimens. Follow-up for overall survival, a key secondary endpoint, remains ongoing.

https://finance.yahoo.com/news/bristol-myers-squibb-2seventy-bio-104500151.html

OptimizeRx revises outlook

The stock price of OptimizeRx (OPRX) fell by over 20% pre-market today. These are the highlights.

– Revenue in the second quarter of 2022 increased 3% to $14.0 million, from $13.6 million as compared to the same year-ago period.

– Gross profit in the second quarter of 2022 increased 12% year-over-year to $9.0 million.

– GAAP net loss totaled $3.9 million or $(0.21) per basic and diluted share in the second quarter.

– Non-GAAP net income in the second quarter totaled $0.7 million or $0.04 per basic and fully diluted shares outstanding. (see definition of this non-GAAP measure and reconciliation to GAAP, below).

– Cash and cash equivalents totaled $87.4 million as of June 30, 2022, as compared to $84.7 million as of December 31, 2021.

2022 Financial Outlook

Based on first half results, the company is updating its full year financial outlook for 2022 and now expects net revenue of $62 million to $68 million, representing year-over-year growth of 1% to 11%, respectively, and gross margins to be between 59% and 62%.

The change to the second half 2022’s outlook is driven by what is perceived to be temporary life sciences industry challenges related to a slowdown in the number of new drug approvals, increased turnover rates at client companies and longer sales cycles associated with larger deal sizes in the funnel.

https://pulse2.com/optimizerx-oprx-stock-why-it-fell-over-20-today/