Sanofi to list drug ingredients business on May 6

 Sanofi (SASY.PA) expects to list its drug ingredients business EUROAPI on May 6, having received approval from French stock market regulator, the pharmaceutical giant said on Friday.

The listing is set to take place shortly after a May 3 shareholder meeting, at which Sanofi's stakeholders will vote on the listing.

Sanofi said the new shares will be distributed to its shareholders at one EUROAPI share per 23 Sanofi shares.

The company confirmed plans to conserve a 30% stake in the business after the listing while the French state will buy a 12% stake through EPIC Bpifrance for up to 150 million euros ($166 million).

L'Oreal (OREP.PA), Sanofi's largest shareholder with a more than 9% stake, and EUROAPI Chief Executive Karl Rotthier have both agreed to a one-year lock-up period after the listing, it added.

EUROAPI makes active pharmaceutical ingredients (APIs) for medicines and will be based from six production sites in Italy, Germany, Britain, France and Hungary.

Sanofi, which last year accounted for half EUROAPI's revenue, said in January that it expects the business to become the world's second-biggest API player with about 1 billion euros in revenue forecast for this year.

The bulk of EUROAPI's share capital, 58%, will be distributed to Sanofi shareholders through a dividend in kind, in addition to a previously proposed 3.33 euros per share cash payout.

https://www.reuters.com/business/healthcare-pharmaceuticals/sanofi-list-drug-ingredients-business-may-6-2022-04-01/

How a Seagen cancer drug with Nobel Prize science might also work in diabetes

 Some diabetes therapies work by ramping up the body’s secretion of insulin to counteract high blood sugar levels. But a team of scientists at the Karolinska Institute believe preserving insulin-producing pancreatic beta cells—rather than overloading them—would be a better diabetes treatment strategy over the long term.

Following that thinking, the team showed that an experimental cancer drug made by Seagen dubbed PX-478 could improve the function of beta cells and restore blood sugar balance in diabetic mice. The results are published in the journal Science Translational Medicine.

Because PX-478 has already been tested in a clinical trial as an anti-cancer drug and was well tolerated in these patients, the Karolinska researchers hope they could quickly move the drug into clinical trials of diabetes after additional animal tests.

PX-478 is an inhibitor of the hypoxia-inducible factor 1-alpha (HIF-1alpha) protein. The 2019 Nobel Prize in physiology or medicine went to three scientists for their discoveries of HIF’s role in how cells respond to low oxygen levels, or hypoxia.

In Type 2 diabetes, continuous insulin resistance sends pancreatic beta cells into overdrive as the cells try to maintain normal blood sugar levels, eventually wearing the cells out. Previous studies have linked the metabolic dysfunction with hypoxia and HIF-1alpha, given the high energy, oxygen-dependent demands of insulin secretion.

Under normal circumstances, HIF-1alpha is quickly degraded. But in diabetic mouse models, HIF-1alpha was stabilized and accumulated in the animals’ pancreatic islets amid hypoxia caused by an increase in metabolic workload, the Karolinska team found.

The researchers treated the diabetic mice with PX-478. In a mouse model of “extreme” Type 2 diabetes marked by early loss of beta cell function, PX-478 prevented the rise of blood glucose. Mice treated with the drug kept plasma insulin concentration elevated, suggesting their beta cells were still working to release insulin to compensate for insulin resistance. By contrast, untreated mice saw their insulin concentration drop.

In another mouse model with reduced functional beta cells, PX-478 treatment brought blood sugar levels under control, whereas hyperglycemia persisted in nontreated mice.

Pancreatic islets isolated from PX-478-treated mice showed hallmarks of improved beta cell function including an increase in insulin content and expression of genes involved in beta cell function and maturity as well as the formation of insulin granules similar to those of nondiabetic control mice.

The drug also showed similar benefits in organoids of human pancreatic cell islets. It cooled the human beta cells down by reducing basal insulin secretion and increasing a response to high blood sugar, the researchers found.

Hypoxia has broad implications in various diseases. And this is not the first time that scientists have found the repurposing potential of PX-478 in a disease beyond cancer. A research team at Yale University previously discovered that PX-478 held promise for lupus nephritis, because it could reduce kidney inflammation from kidney-infiltrating T cells. 

Because insulin production declines during diabetes, therapeutic strategies have so far mainly focused on improving beta cells' insulin production. Other research efforts that have also focused on the preservation of beta cell function, including targeting the protein TXNIP by scientists at the University of Alabama at Birmingham.

“Current therapies targeting beta cells have only a temporary positive effect on insulin secretion,” Per-Olof Berggren, the current study’s co-senior author, said in a statement. “In the long-term, these drugs lead to beta-cell exhaustion.”

Next up, the Karolinska team aims to test PX-478’s effect on human pancreatic beta cell function in a “humanized” mouse model in which immunosuppressed mouse is transplanted with human islets.

https://www.fiercebiotech.com/research/how-seagen-cancer-drug-might-also-work-diabetes

After FDA hold, CytoDyn will appeal for pharma partnerships to save leronlimab

 With CytoDyn's lead drug on FDA clinical hold, the troubled biotech will go searching for partners to rescue key programs and keep afloat.

Meanwhile, the board is actively searching for a new CEO to replace Nader Pourhassan, Ph.D., who was ousted in January.

The company provided a sweeping corporate update in a conference call Thursday morning, after announcing at market close the day before that the FDA had placed two separate clinical holds on leronlimab. The regulatory shutdown includes a partial hold on CytoDyn’s HIV work and a full hold on the COVID-19 program, according to an after-market release issued Wednesday.

"We will be focused on setting up the company for future success by restoring credibility and determining our most advantageous path forward with the goal of maximizing shareholder value," said Antonio Migliarese, CFO and interim president, on the call.

Migliarese then listed the priorities, which were many: "We plan on doing this by strengthening our clinical operations and prioritizing patient safety, addressing the concerns noted in the partial clinical hold letter received for HIV and the full clinical hold letter received for COVID-19, enhancing leadership with the board, CEO and Scientific Advisory Board, addressing legal and financial issues."

Not to mention analyzing new data in HIV, revamping the timeline for a biologics license application in the indication, releasing results in non-alcoholic steatohepatitis and finding new partnerships with pharmaceutical companies to fund all this work. All that for a company that does not currently have a CEO.

CytoDyn has touted leronlimab as having potential in multiple indications, but the therapy has struggled in the clinic against COVID, and the company has equally faced difficulties in getting regulatory submissions locked down for HIV. The company said in announcing the holds that clinical trials underway in the COVID program in Brazil would be paused pending results from the data safety monitoring committee.

Chief Medical Officer and Head of Business Development Scott Kelly said the company decided to pause the Brazilian trials in COVID because of two cardiac events. The studies feature very sick patients with cardiac and pulmonary manifestations of the disease, he added.

The study remains blinded, meaning CytoDyn does not know whether the patients who suffered the cardiac events received leronlimab or placebo. 

"We discussed this in depth with the physician investigators in Brazil who have extensive pulmonary and critical care expertise, and they believe the events were consistent with the natural course of COVID and nothing out of the ordinary of their experience and prior COVID-19 trials," Kelly said. 

CytoDyn opted to pause the program "out of an abundance of caution," knowing that the data safety monitoring committee would be meeting anyway in April. 

"I want to be clear that this was our decision. We thought it was the right thing to do," Kelly said. Once the committee clears the trial to continue, CytoDyn plans to resume clinical activities.

As for the holds, Kelly said the agency wants aggregated safety data from all the indications leronlimab has been tested in before any further work can be done in the U.S. He called this a "solvable problem," and pledged to complete the work on an eight- to 10-week timeline. Kelly stressed that the company is not enrolling in the U.S. for the COVID program, and the HIV program at issue is a long-term extension study that has wrapped up. 

For the HIV program, CytoDyn said Wednesday that "these patients will be transitioned to other available therapeutics and no clinical studies can be initiated or resumed until the partial clinical hold is resolved." While the company works with the FDA to resolve the holds, no new studies may be started in the COVID-19 program.

The company will also re-evaluate a biologics license application in HIV, which will mean a "delay in clinical activities," according to Chris Recknor, M.D., senior executive VP of clinical operations. The submission will be on hold while the safety data is compiled for the FDA with a new CRO. 

Regarding the search for a new CEO, Board Chair Tanya Urbach said a search committee has been formed. 

"We are excited about the overall quality of the candidate pool and will continue in our efforts to identify the company's next chief executive officer," she said. 

CytoDyn also provided a broad update to its clinical programs, including plans to advance leronlimab in NASH. The company has also been contacted by multiple academic institutions for access to the drug to conduct preclinical studies in glioblastoma multiforme, Alzheimer's disease and others, according to Kelly. Another study could someday look at using leronlimab in COVID long haulers, and there's been interest in combining the therapy with CAR-T treatments in cancer, he said.

All of these indications have confounded major drugmakers for decades, even companies that specialize in diseases like NASH or Alzheimer's. 

For all or most of these initiatives, CytoDyn needs help. Kelly, and other executives said over and over that they would be seeking partnerships to move programs forward. This will help CytoDyn "advance our development efforts and value creation with minimal investment," according to Migliarese.

"As we all know, in clinical trials, it's very costly, but we believe we can leverage the experience of others that are experts in each chosen field," Kelly said. 

He declined to name names, but said, "We have companies under NDA right now and we are advancing those discussions for multiple different applications for leronlimab." 

Another issue that received scant mention is CytoDyn's many legal battles, which include an investigation from the Department of Justice and the Securities and Exchange Commission. Migliarese said the company is fully cooperating with the investigators and "doing our best to expeditiously wrap up the various other legal matters of the company." That includes a spat with a former contract research organization. 

CytoDyn's remaining leadership has a tough to-do list. But the conference call was markedly more sane compared to those previously held when Pourhassan was in charge. In May last year, he begged investors to stop trashing the FDA after the agency's public smackdown of the company over its leronlimab claims. Pourhassan took a barrage of questions from angry investors. But on today's call, Kelly and the team took pre-screened written questions, mostly those surrounding clinical trial updates or the pharma partnerships. 

https://www.fiercebiotech.com/biotech/cytodyns-leronlimab-slapped-fda-holds-covid-19-hiv-programs

Missouri House slated to pass sweeping new abortion bill

 The Republican-led Missouri House is set to pass legislation to defund Planned Parenthood, criminalize mail-order abortion medications, and allow wrongful death lawsuits in rare cases when infants are born alive after an abortion attempt and the infant then dies or is injured.

House lawmakers earlier this week blocked an attention-grabbing amendment to make it illegal to “aid or abet” abortions that violate Missouri law, even if they occur out of state.

Instead, the GOP swapped in another amendment that would make it a crime to provide abortion-inducing medications to women. Doctors could still provide those medicines.

Republican Rep. Brian Seitz, who sponsored the medication abortion bill, said the issue with the proposal to penalize helping women travel out of state for abortions was that it has not been vetted through a committee like his measure has.

If Roe v. Wade is overturned and abortion is banned in Missouri, Seitz’s change would prohibit telemedicine abortions through medications.

“It’s very important that states, especially typically pro-life states, have legislation already in place for the possible overturn of Roe v. Wade,” Seitz said.

House members packed the abortion policies together in an omnibus bill Tuesday in hopes of passing the proposals by lawmakers mid-May deadline despite ongoing GOP infighting that’s causing work in the Senate to move at a glacial pace.

Advocates of Planned Parenthood of the St. Louis Region and Southwest Missouri spokeswoman Bonyen Lee-Gilmore in a statement called the legislation “a kitchen-sink approach to banning reproductive freedom in Missouri.”

“It unlawfully blocks Medicaid patients from preventive care at Planned Parenthood, it spreads inflammatory rhetoric, and seeks to ban common medications used for miscarriages, labor and delivery, and abortion,” she said.

Under the amended bill, family members could also file wrongful death suits if infants born alive after an abortion attempt are injured or later die as a result of the attempted abortion. If the pregnancy is the result of rape, the bill would not allow the rapist to sue.

Republican Rep. Hannah Kelly, who sponsored a bill banning fetal tissue donations onto which the other abortion amendments were added, told colleagues during House floor debate Tuesday that the born-alive provision represents a chance for justice.

Democratic Rep. Keri Ingle warned that the threat of lawsuits would pit families against each other.

Instances of babies being born alive after an induced pregnancy termination are extremely rare.

A review by the U.S. Centers for Disease Control and Prevention of infant mortality data from 2003 and 2014 showed 143 deaths were of infants that displayed signs of life after an induced termination. That was a tiny fraction of the 315,000 infant deaths during those 12 years, a period that also included 49 million live births.

In a majority of those cases, the abortion was induced due to a maternal complication or congenital anomaly in the fetus.

Mary Ziegler, a Florida State University law professor, said current homicide laws could already offer protections for infants born alive after abortions.

She said similar proposals nationally and in other state have mostly been used as a way for Republicans to show their opposition to abortion while forcing Democrats to argue against bills with the stated intent of cracking down on infanticide.

“What they’ve been historically designed to do is to frame the debate around issues that are really uncomfortable for supporters of abortion rights,” Ziegler said of similar proposals.

The Missouri measure also includes yet another attempt by Republican lawmakers to strip Planned Parenthood of any public funding, including clinics that do not provide abortions.

Lawmakers were able to stop money from going to Planned Parenthood in the 2019 fiscal year by forgoing some federal funding to avoid requirements that the clinics be reimbursed if low-income patients go there for birth control, cancer screenings and other preventative care. Missouri instead used state money to pay for those services.

But the Missouri Supreme Court in 2020 ruled that lawmakers violated the constitution by making the policy change through the state budget, forcing the state to reimburse Planned Parenthood for health care provided to Medicaid patients.

It’s unclear whether blocking funding through a policy bill instead of the budget will work, but Republican lawmakers have said they’re hopeful enough to try again.

A vote to send the sweeping bill to the GOP-led Senate could come as early as next week.

https://apnews.com/article/abortion-business-health-lawsuits-missouri-b795a9cf11a28488b875f774c3b414c2

Jayapal: Federal protections for trans kids ‘cannot wait any longer’

 Rep. Pramila Jayapal (D-Wash.), who is a mother to a transgender child, penned an op-ed published by Teen Vogue on Thursday, International Transgender Day of Visibility, calling for federal protections for transgender children.

“Like hundreds of thousands of parents with transgender kids across the country, I want to do everything I can to support my daughter as she strives to embrace who she is and live as her most authentic self,” Jayapal wrote.

“But I also worry deeply that the world we live in now doesn’t receive her in the same way — that she will face violence and barriers that we know are there for too many transgender people.”

The congresswoman noted the higher degree of harassment and mental illness that transgender children face and accused Republicans of worsening these problems by using transgender youth as a “political wedge issue.”

She pointed to the bill recently passed in Texas that classified gender-affirming care for children as child abuse. Jayapal called the legislation “unconstitutional” and “openly discriminatory and hostile to the well-being of these children.” The bill was halted by a Texas appeals court earlier this month.

The congresswoman also noted a similar bill in Idaho that would make gender-affirming youth health care a felony. The measure was passed in the Idaho state House of Representatives earlier this month, but Idaho Senate Republicans declined to vote on it on the basis that it undermined parental rights and allows the government to interfere in parents’ decisions for their children.

“Both of these bills are fueled by a cocktail of ignorance, transphobia, and malice for trans kids, their parents, and the doctors and the communities who want to help them. The bills are an outrageous violation of human rights,” Jayapal wrote. “That’s why today, as we celebrate Transgender Day of Visibility, I stand with every single trans child and the parents who support them.”

“The suffering of transgender children is not inevitable. It is our job — as leaders, as parents, as legislators — to push back on the attacks and to move us forward again toward true equality and justice,” she added.

https://thehill.com/news/house/3255919-jayapal-federal-protections-for-trans-kids-cannot-wait-any-longer/

How China’s latest Covid lockdowns affect American businesses ihere

 China’s worst Covid wave since the initial shock of the pandemic has cut into annual revenue projections for roughly half of American businesses in the country, a survey showed Friday.

The Beijing-based American Chamber of Commerce in China and its Shanghai counterpart surveyed 167 members operating in China, including 76 manufacturers, this past Tuesday and Wednesday.

The metropolis of Shanghai, where many foreign businesses are located, entered a two-part lockdown this week as municipal authorities sought to control a brewing number of Covid cases. Those measures followed shorter lockdowns in the tech hub of Shenzhen, the manufacturing hub of Dongguan and travel restrictions across the country.

The survey found that 54% of respondents have lowered 2022 revenue projections for the year due to the latest Covid-19 outbreak.

Among manufacturers, more than 80% reported slowed or reduced production, as well as supply chain disruptions.

Nearly all, or 99%, of respondents said the latest outbreak had affected them.

Since the pandemic began in 2020 and China tightened restrictions on international travel, foreign businesses in China have complained of long quarantine requirements upon arrival and difficulties of bringing in senior management or technical staff.

If China’s current Covid-19 restrictions remain in place for the next year, half of respondents to this week’s AmCham survey said they would reduce investment. Nearly 75% of respondents said maintaining those restrictions would reduce their revenue and profit.

And nearly 20% of manufacturers said they would move manufacturing or operations out of mainland China if the Covid-19 restrictions remained.

While just about half of respondents overall were satisfied with China’s efforts to control Covid’s spread, the top three aspects of dissatisfaction were the length of required quarantines, restrictions on travel to China and the lack of flights to China.

The top three recommendations from survey respondents were to allow for home quarantine or other options, simplify requirements for coming to China and allow more flights into the country.

The number of new Covid cases and deaths reported in mainland China remains well below that of major countries.

https://www.cnbc.com/2022/04/01/amcham-survey-on-chinas-latest-covid-lockdowns-american-businesses.html

Groups urge Biden to reject potential WTO 'concept' on COVID-19 vaccine barriers

 Médecins Sans Frontières, Oxfam America, Amnesty International and other top civil society groups on Wednesday called on US President Joe Biden to reject a potential agreement on COVID-19 vaccine intellectual property rights in the World Trade Organization.

In a letter, the groups called the proposal a “rehash” of an EU position that was far from the rights exemption Biden supported in May 2021 to speed up vaccines for developing countries.

“This leaked text … would impose new conditions limiting existing WTO rules, which now allow countries to issue compulsory licenses for patented products,” the organizations said.

They noted that India and South Africa, which had been working on the compromise language with the US and the EU, had not yet formally approved the “concept”.

U.S. Trade Representative Katherine Tai on Wednesday told U.S. lawmakers that there was no agreement on what she called the “concept” of a compromise developed during discussions facilitated by WTO Director-General Ngozi Okonjo-Iweala.

A text for the proposed compromise, which Reuters saw earlier this month, sought to waive IP rights to COVID-19 vaccines and supplies. It must be completed and accepted by the 164 member states of the WTO. Read more

Some critics argue that the potential deal does not go far enough beyond a mandatory vaccine licensing regime, while others see it as hurting large companies’ IP rights.

The groups called on Biden to redouble its efforts to negotiate an “actual exemption” to increase COVID-19 vaccine production.

European civil society groups have expressed similar concerns in a separate letter to EU officials.

The US groups said the potential deal would add burdensome conditions to WTO rules by requiring the identification of all relevant patents, data that were not readily available.

“If adopted as it stands, this text, while continuing to privilege Big Pharma monopolies and profits, will continue to deny access to life-saving COVID-19 vaccines and treatments to millions around the world,” the groups wrote. .

https://www.reuters.com/world/us/groups-urge-biden-reject-potential-wto-concept-covid-19-vaccine-barriers-2022-03-30/