Dyne's Exon-51 Skipping DMD Therapy Moves Forward on FDA Go Sign

 The U.S. Food and Drug Administration has lifted the clinical hold on Dyne Therapeutics’ clinical study of DYNE-251 in Duchenne muscular dystrophy (DMD) patients amenable to skipping exon 51. They expect the Phase I/II trial to launch by mid-year.

The agency placed a hold on the company’s Investigational New Drug (IND) application in January, requesting more clinical and non-clinical data for the therapy.

DMD is a genetic disease marked by progressive muscle degeneration and weakness. It is caused by mutations to the dystrophin protein, which codes for muscle. It is the largest gene in the body, which is why traditional gene therapy technology is not utilized - the gene is too large for the typical viral vectors. The disease primarily occurs in boys and typically leads to impaired pulmonary function and acute respiratory failure and death.

Dyne is Targeting Exon 51

Most of the treatments in existence and experimental therapies involve a technology known as exon skipping. These therapies are a type of RNA splicing that causes cells to “skip” over mutated or misaligned segments (exons) of genetic code. This results in a truncated but still functional protein. Dyne-251 is being developed for DMD amenable to exon 51 skipping. It is made up of a phosphorodiamidate morpholino oligomer (PMO) conjugated to a proprietary Fab (antibody fragment).

“Today marks a significant step in our journey to build a DMD franchise to serve people across the globe with Duchenne mutations amenable to exon skipping,” said Joshua Brumm, Dyne’s president and chief executive officer. “The clearance of our first IND is an important achievement for Dyne and we appreciate the partnership with the FDA throughout this process. Our team has worked extensively with key opinion leaders, patient advocacy groups and individuals living with DMD to thoughtfully design and executive our global multiple-ascending dose Phase I/II clinical trial of DYNE-251.”

The study will be global and is a multiple ascending dose (MAD) study with a long-term extension study. Dyne plans to enroll 30 to 50 ambulant and non-ambulant males with Duchenne ages four to 16 years whose dystrophin mutations are amenable to exon 51 skipping therapy.

“We believe we are well-positioned to deliver on our commitment of initiating dosing in both of our DMD and DM1 programs in mid-2022. The entire Dyne team is proud of the progress we have made to advance our mission and address the urgent need to bring new therapeutic options to people living with serious muscle diseases,” Brumm added.

The Current DMD Treatment Space

As of March, there were five drugs approved by the FDA to treat DMD. They include Sarepta Therapeutics’ Amondys 45 (casimersen), Vyondis 53 (golodirsen) and Exondys 51 (eteplirsen), which was the first drug to be approved in the space. The others are NS Pharma’s Viltepso (viltolarsen) and PTC Therapeutics’ Emflaza (deflazacort).

Other companies working on treatments for DMD include Pfizer, Genethon and Solid Biosciences, which are developing gene therapies. However, they have been finding serious side effects.

In May, Pfizer, Sarepta, Genethon and Solid partnered with academic experts to work on ways of minimizing the side effects they are finding with the adeno-associated virus (AAV)-based gene therapies for DMD. All of their experimental therapies use the AAV to deliver different versions of a shortened dystrophin transgene driven by different promoters.

All four companies had observed serious adverse events (SAEs) with these therapies, marked by muscle weakness and variable cardiac involvement. However, all had similar clinical presentations and time courses. The SAEs involved five patients across three clinical trials, all occurring about three to seven weeks after the initial gene therapy infusion.

The group believes these SAEs are a “specific transgene/genotype-related ‘class effect.’” The SAEs only occurred in patients with specific genomic deletions, including N-terminal epitopes, which are present in the transgene protein. Pfizer had one death associated with its Phase Ib study in 2021, but the hold has since been lifted.

https://www.biospace.com/article/fda-lifts-hold-on-dyne-s-duchenne-muscular-dystrophy-study/

Arrowhead Initiates Phase 1/2a Studies for Two Pulmonary Candidates

 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has dosed the first subjects in two Phase 1/2a clinical trials of ARO-MUC5AC and ARO-RAGE, the company’s investigational RNA interference (RNAi) therapeutics designed to reduce production the of mucin 5AC (MUC5AC) and the receptor for advanced glycation end products (RAGE), respectively, as potential treatments for various muco-obstructive and inflammatory pulmonary diseases.

https://finance.yahoo.com/news/arrowhead-pharmaceuticals-initiates-phase-1-113000171.html

Shanghai to carry out two new rounds of mass Covid testing

 China's city of Shanghai has announced two new rounds of mass Covid-19 testing of most of its 25 million residents over a three-day period, citing the need to trace infections linked to an outbreak at a karaoke lounge.

The city government said on Tuesday on its official WeChat account that all residents in nine of the city's 16 districts would be tested twice from Tuesday to Thursday. 

People in parts of three other districts would also have to undergo tests.

The testing was needed because multiple Covid infections found this week were linked to a karaoke lounge, which had been visited by residents from several districts, it said.

"No household or person should be missed," the city government said of the testing.

During the testing, people living in the affected districts would be required to show a test taken within the last two days to leave their homes, it said.

Shanghai reported eight new local Covid cases on Monday, seven of which it said were found in quarantined areas.

Test required to enter public areas

City lockdowns and repeated mass testing in China, part of its zero-Covid policy that aims to eradicate all outbreaks, have brought case numbers down but many of the measures have fuelled anger and taken a toll on the economy.

The city already requires all of its districts to organise mass testing of residents every weekend until the end of July.

Residents also need to test themselves every three days in order to enter public areas such as shopping malls or take public transport.

Although China's most populous city has lifted a two month-long lockdown of its 25 million residents, it still imposes targeted curbs on movements whenever a Covid case is found outside quarantined areas.

The northwestern city of Xian, which reported 18 local infections in a flare-up driven by the BA.5.2 sub-variant, will from Wednesday suspend operations at various entertainment venues, dining at restaurants and big events for seven days, a government official said.

https://www.trtworld.com/asia/china-s-shanghai-to-carry-out-two-new-rounds-of-mass-covid-testing-58584

'Abortion Worries Heightened for Unauthorized Immigrants'

 Last week calls from Texas began flooding into a national abortion assistance hotline with Spanish-language operators: One woman called afraid to fly to New Mexico because of her immigration status. Another woman said she would have to keep her pregnancy because she feared deportation if she crossed state lines. A third worried that she would be detained by immigration authorities if she used public transportation to travel.

Penelope DiAlberto, a regional case manager for Texas at the National Abortion Federation, said the three women were among a massive spike in calls to their hotline on the Friday and Saturday after the U.S. Supreme Court overturned the landmark 1973 Roe v. Wade ruling that had recognized women's constitutional right to abortion.

While concerns are rising among many women in the wake of the ruling, women with uncertain immigration status face additional barriers and everyone from abortion providers to U.S. government agencies have been scrambling to determine what will happen going forward.

Thirteen states passed laws that aimed to trigger full or partial bans to abortion in the wake of the Supreme Court ruling, radically reshaping access to abortion across the country.

The administration of U.S. President Joe Biden, a Democrat, has pledged to defend the rights of women to travel to other states for medical care.

But women without legal immigration status are more likely to face difficulties crossing state lines to access abortions if the procedure is banned where they live, said Lupe Rodriguez, executive director of the New York-based advocacy organization the National Latina Institute for Reproductive Justice.

Several states with so-called "trigger" laws - such as Texas, Arizona and Florida - have large immigrant populations but do not allow people without legal status to get a driver's license, according to a 2021 report by the National Immigration Law Center.

The U.S. Border Patrol maintains a network of some 110 checkpoints along U.S. roads, the majority of which are located 25 to 100 miles (40-160 km) inland of the country's borders. Fear of being caught at an immigration checkpoint and possibly being deported makes it "virtually impossible" for many people living in the country illegally to travel across state lines, Rodriguez said.

TRAPPED IN CUSTODY

Biden officials are exploring ways to provide abortion access for pregnant women and girls in U.S. immigration custody in states with bans, four U.S. officials who requested anonymity to discuss the government plans told Reuters.

Many federal shelters for unaccompanied children apprehended at the U.S.-Mexico border are located in Texas, where a Republican-backed law that went into effect in September banned abortions at six weeks.

For the past nine months, U.S. health officials have been flying or driving minors from Texas shelters to other states for abortions. Advocates say more guidance is needed now, and fast.

"Time is really of the essence when someone needs access to abortion," said Brigitte Amiri, deputy director at the American Civil Liberties Union's reproductive freedom project.

Federal judges in several states have halted the bans, but confusion reigns as the legal wrangling continues.

A 27-year-old woman from Honduras who now lives in Texas, and asked to withhold her name for privacy reasons, said she lost her student visa after she dropped out of college following the stress of an abortion she got in 2015. Now that she has no legal status in the United States, she said, she wouldn't know what to do if she found herself with an unwanted pregnancy again. "In the position I am now, not having my papers, why would I risk myself?" she said.

'Reporting by Sofia Ahmed in New York'

https://www.usnews.com/news/world/articles/2022-07-05/abortion-worries-heightened-for-unauthorized-immigrants-in-the-u-s

Virpax Pursues OTC Medical Device Pathway for Antiviral Barrier

 Virpax® Pharmaceuticals, Inc. ("Virpax" or the "Company") (NASDAQ: VRPX), a company specializing in developing non-addictive products for pain management, post-traumatic stress disorder, central nervous system (CNS) disorders and anti-viral indications, today announced it will pursue an OTC Intranasal Medical Device Consumer regulatory pathway for AnQlar™, the Company’s product candidate being developed as a prophylactic antiviral barrier against influenza and SARS-CoV-2.

"We believe that AnQlar, upon successful development and commercialization, may be a 24-hour prophylactic medical device that can be used as an intranasal barrier against COVID, Influenza and most negatively charged viruses, including the Rhinovirus. We expect the OTC non-prescription Medical Device pathway to provide a faster drug development timeline and global approval track than the OTC non-prescription New Drug Application pathway that we had originally pursued for AnQlar," stated Anthony P. Mack, Chairman and CEO of Virpax.

"Additionally, we intend to validate AnQlar’s claims and assess its value for commercialization in North America, Europe and Asia," continued Mr. Mack. "We now have two product candidates, AnQlar and Epoladerm™, in our OTC pipeline and will seek to license out or partner these assets as we continue to focus our efforts on our prescription drug pipeline."

To support the OTC Medical Device application, Virpax plans to submit AnQlar’s completed in-vitro study, ex-vivo study using human mucosal cells, in-vivo study in rats, toxicology study and its pharmacokinetics (PK) characteristics studies to the FDA. Additionally, the Company will include AnQlar’s completed safety-pharmacology studies, drug-drug interaction studies and its virology studies evaluating AnQlar’s antiviral properties against two variants of SARS-CoV-2 in a SARS-CoV-2 mouse model to the FDA. For the OTC medical device application, Virpax anticipates that it will have to complete stability testing, human factors testing for medical devices, safety studies and supplementary in-vitro studies.

https://finance.yahoo.com/news/virpax-pursues-otc-medical-device-130000414.html

CureVac files patent lawsuit in Germany against BioNTech

 CureVac has filed a patent lawsuit in Germany against BioNTech over its use of mRNA technology, marking one of the first known cases of a company going to court amid the fierce competition to develop a vaccine against the coronavirus.

The German-based company is seeking "fair compensation" from BioNTech and two subsidiaries for infringement of its intellectual property rights, it said on Tuesday.

CureVac said that its claim to intellectual property rights was based on more than two decades of work on mRNA technology that was used by BioNTech and Pfizer for the development and sale of their Comirnaty coronavirus vaccine.

However, CureVac said that it was not seeking an injunction, nor does it intend to take legal action that would impede the production, sale or distribution of the vaccine.

"At the height of the pandemic, it would not have occurred to any of us to point out patent infringement. Now that there is better control over the pandemic, we believe it is the right time to do so," a spokesperson for CureVac said.

BioNTech declined to comment when contacted by Reuters.

The COVID-19 pandemic, which began in China, has killed more than 6.3 million people and spurred a race among pharmaceutical companies to be the first to develop a vaccine, with BioNTech and Pfizer coming to dominate the field.

After failed efforts to bring a COVID-19 vaccine to market last year, CureVac intensified its work with partner GlaxoSmithKline on improved versions of vaccine.

CureVac and GSK said in April that their second-generation vaccine candidate targeting two recent COVID-19 variants had been shown to be highly effective in pre-clinical studies on mice.

German-listed CureVac's shares extended gains after the news, rising 2.5% at 13.90 euros at 1245 GMT.

BioNTech shares were down 3.65% at 145.25 euros.

The court in Duesseldorf, where CureVac submitted its lawsuit, declined to comment.

https://finance.yahoo.com/news/curevac-files-patent-lawsuit-germany-113727730.html

Syros to Raise $190 M Via Merger with TYME, Concurrent Private Placement

 Combined Company Will Operate as Syros Pharmaceuticals and Continue to Advance Syros’ Ongoing Clinical Programs

Syros Expects to Have Cash Into 2025; At Least a Year Past SELECT-MDS-1 Pivotal Data

Now Planning to Initiate Phase 3 Clinical Trial of SY-2101 in APL 2H 2023

Syros to Host Conference Call at 8:30 AM ET Today

Syros will host a conference call today, July 5, 2022 at 8:30 a.m. ET, to discuss the transactions. Participants may register for the conference call here. While not required, it is recommended that participants join the call ten minutes prior to the scheduled start.

A live webcast of the call will also be available on the Investors & Media section of the Syros website at http://ir.syros.com.

https://finance.yahoo.com/news/syros-raise-approximately-190-million-110000910.html