A strange trend for Uniqure

Uniqure’s reluctance to disclose specific data on its Huntington’s gene therapy AMT-130 has stung it in the past, so today’s reveal has been welcomed by investors. In four evaluable patients in the low-dose cohort of the ongoing phase 1/2 trial, mean levels of mutant huntingtin protein (mHTT) in the cerebrospinal fluid fell by between 58.3% at 12 months, versus 16.8% among three evaluable patients in the sham control group. But the odd trend over time – sham patients were doing poorly until the one-year point, when they staged a startling reversal – has raised questions. On a call today management attributed this to the size of the trial, saying that one of the sham patients was an outlier and distorted the overall picture. Nonetheless Uniqure is up 13% in early trade, likely because the reduction in mHTT was at the higher end of what Uniqure had hoped for. But this is just biomarker data; results on functional endpoints, including from a 16-patient high dose cohort, will come in 2023, and the company said that in order to get approval – even accelerated approval – it will need to show clinical benefit. The group has no plans to seek a partnership. 

Source: Company presentation.

https://www.evaluate.com/vantage/articles/news/trial-results-snippets/strange-trend-uniqure

Biden Admin Plans 6-Figure Compensation for Havana Syndrome Victims

 The Biden administration is planning to compensate victims of Havana syndrome, the anomalous health incidents affecting U.S. diplomats and intelligence officers worldwide, with payments ranging from $100,000 to $200,000, sources familiar with the matter said Thursday.

The proposed rule, which is expected to be published in the coming days, comes after the U.S. Congress last year passed the Havana Act, which authorizes the State Department, CIA and other U.S. government agencies to provide payments to staff and their families who have been affected by the syndrome during assignment.

About 200 U.S. diplomats, officials and family members overseas are believed to have been struck by the mysterious ailment — with symptoms including migraines, nausea, memory lapses and dizziness.

It was first reported among U.S. officials in Havana, the Cuban capital, in 2016, but since then has been reported in dozens of locations, including in Russia and China, as well as in Europe and Latin America.

Despite years of investigation, the U.S. government has been unable to determine the cause or whether an adversary such as Russia or China is responsible.

A CIA investigation whose conclusions were released earlier this year said the agency had found no evidence of state actor involvement in the thousand cases it had looked into but said it was continuing to investigate two dozen unexplained cases.

The State Department's draft rule is expected to remain open for comments for 30 days before becoming a final rule in a process coordinated with the Office of Management and Budget, people familiar with the matter said.

The rule is expected to include the criteria for eligibility, sources said, adding that the exact payment amounts were still being finalized.

The State Department declined to comment on the payments but said the Havana Act requires the agency to publish implementing regulations. "We will have more details to provide on that process soon," a department spokesperson said.

Sufferers and lawmakers have complained that U.S. agencies have not taken the illness seriously enough.

Secretary of State Antony Blinken in November appointed veteran diplomat Jonathan Moore to lead the agency's task force handling the issue. He vowed to leave "no stone unturned to stop these occurrences as swiftly as possible."

https://www.voanews.com/a/biden-administration-plans-six-figure-compensation-for-havana-syndrome-victims-/6631096.html

Mexico records most daily Covid-19 cases since February, signaling fifth wave

 Mexico reported 16,133 new Covid-19 cases in the country yesterday, the highest daily number reported since late February, according to data released by the Health Ministry.

The increase is a signal that another wave of the virus is spreading through the country, experts say.

“What we have been identifying over the last nine weeks is a progressive increase in the frequency of cases,” Deputy Health Minister Hugo Lopez-Gatell said in a regular news conference Tuesday.

Lopez-Gatell said most cases in the country are of the Omicron BA.4 and BA.5 subvariants, which cause cold-like symptoms.

“And even more encouraging is that deaths are also being kept under control,” he said.

Mexico recorded an average of 24 deaths a day over the past seven days, according to Health Ministry data.

The ministry said Tuesday that 4 per cent of general hospital beds were filled with Covid-19 patients, while 1 per cent of emergency beds were filled.

Lopez-Gatell said the rate at which cases are increasing is encouraging “because it suggests that ... the protection that we all have, either because we suffered from Covid or because we were vaccinated, or both, works and makes the spread slower than it was.”

Earlier this month, Mexico opened registration for children ages 5 to 11 to receive their first dose of the Covid-19 vaccine. 

https://www.malaymail.com/news/world/2022/06/24/mexico-records-most-daily-covid-19-cases-since-february-signaling-fifth-wave/13974

Abortion pills over the counter? Major hurdles seen in widening U.S. access

 A pill used to terminate early pregnancies is unlikely to become available without a prescription for years, if ever, experts say, as the conservative-leaning U.S. Supreme Court is expected to dramatically curb abortion rights in the coming weeks.

The Biden administration is considering several options to increase access to so-called medication abortions, which can be administered at home, to help women in the many U.S. states that are expected to severely limit or outright ban abortions following the upcoming Supreme Court ruling.

The pill, mifepristone, is used in combination with a second drug called misoprostol to induce an abortion up to 10 weeks into a pregnancy and is heavily restricted – only available through a certified doctor’s prescription. Abortion rights activists have stepped up calls to make it available for anyone to buy at pharmacies without a prescription.

Medical and regulatory experts interviewed by Reuters say the process could take years. Drugmakers would need to conduct new studies showing that a consumer can safely use the product based on directions on its packaging, without the guidance of a doctor or other provider.

The two companies that make the pill for the U.S. market have shown no interest in doing so. Should they choose to conduct the research, any approval from the U.S. Food and Drug Administration (FDA) would become a target for lawsuits from abortion opponents that could delay implementation for years, they say.

“The hard part that I see is getting the evidence or the agreement that no prescriber is needed at all,” said Susan Wood, a former Assistant Commissioner for Women’s Health at the FDA.

“I personally don’t see it happening in the next couple of years,” said Wood, now director of George Washington University’s Jacobs Institute of Women’s Health.

The Supreme Court is due to decide on a new case that could overturn the landmark Roe v. Wade ruling that made abortion legal in the country in 1973. Last month, a leaked draft ruling suggested that a majority of justices back reversing the decision. Should that happen, nearly half of the 50 U.S. states are expected to ban or heavily restrict the procedure – which would dramatically limit access for millions of women.

THE NEXT BATTLE

Access to abortion pills is expected to become the next big battle, as their use is harder to track. The FDA has already made it easier for certified doctors to prescribe the pills by relaxing some restrictions.

The agency now allows doctors certified to prescribe mifepristone to do so after a telehealth visit rather than in-person and patients can receive it by mail, making it easier for women in U.S. states that already restrict its use.

The White House has already considered making abortion pills available online and from pharmacies abroad, with a prescription. However, the importation possibility has already been curtailed by Congress in broader legislation about drug regulation.

An over-the-counter designation would make it much easier for pregnant women to access the pills in states that seek to restrict their use. For example, they could more easily be mailed to a patient from a friend or supporter in a state where they are not banned.

An FDA spokesperson declined to comment on whether over-the-counter use of abortion pills has been considered. A spokesperson for Danco Laboratories, a manufacturer of mifepristone, said that it does not plan to seek over-the-counter approval. GenBioPro, the second maker of mifepristone for the U.S. market, did not respond to requests for comment.

ARE THEY SAFE?

Medication abortion involves two drugs, taken over a day or two. The first, mifepristone, blocks the pregnancy-sustaining hormone progesterone. The second, misoprostol, induces uterine contractions.

When taken together, the pills halt the pregnancy and prompt cramping and bleeding to empty the uterus, in a process similar to miscarriage.

Abortion rights activists say the pills have a long track record of being safe and effective, with no risk of overdose or addiction. In several countries, including India and Mexico, women can buy mifepristone and misoprostol without a prescription to induce abortion.

“Medication abortion really does meet all the FDA criteria for an over-the-counter switch,” said Antonia Biggs, associate professor at the University of California, San Francisco’s Obstetrics, Gynecology and Reproductive Sciences department.

A study https://journals.lww.com/greenjournal/Fulltext/9900/Comprehension_of_an_Over_the_Counter_Drug_Facts.463.aspx by Biggs and colleagues found that the majority of participants would understand a medication abortion over-the-counter label. Biggs said she was not in talks with drugmakers over her research.

The Charlotte Lozier Institute and Susan B. Anthony List, which advocate against abortion, have said that the FDA decision to relax restrictions on mifepristone ignored data on complications and put women at risk.

Others point to the decade-long legal fight for over-the-counter Plan B, a form of emergency contraception taken within days of sexual intercourse to prevent a pregnancy. Approval for women 18 and over was granted in 2006 and for use by women of all ages in 2013.

“There was very strong support that you did not need a prescriber,” said Wood, who resigned from the FDA in 2005 over the delay.

“Everybody under the sun agreed except for a small group of people who somehow had an enormous political influence.” 

https://nationalpost.com/pmn/news-pmn/crime-pmn/abortion-pills-over-the-counter-experts-see-major-hurdles-in-widening-u-s-access

Sanofi, GSK Report Successful Vaccine Study Against Omicron

 Sanofi SA said Friday that its coronavirus booster vaccine, developed alongside Britain's GSK PLC, has produced successful results against the Omicron variant of the coronavirus in an efficacy study.

The French biopharmaceutical company said its vaccine candidate showed efficacy against the virus in an environment of high Omicron variation. It showed 72% efficacy against the strain in adult, as well as a favorable safety and tolerability profile, the company said.

Along with positive data from two previous trials, the results will be submitted to regulatory authorities for approval, Sanofi said.

The results "indicate the potential of Sanofi-GSK's next-generation Beta-based booster to be a relevant response to public health needs," the company said.

https://www.marketscreener.com/quote/stock/SANOFI-4698/news/Sanofi-GSK-Report-Successful-Vaccine-Study-Against-Omicron-40803704/

Leerink's Pro-forma Analysis Of Speculated Merck/Seagen Deal

 

• SVB Securities conducted a pro-forma analysis of the financial impact to Merck & Co Inc (NYSE: MRK) from a potential acquisition of Seagen Inc (NASDAQ: SGEN).

• The analysts refrain from commenting on the probability of the deal happening. The analysis suggests that the short-term impact on EPS from the potential acquisition will likely be meaningfully dilutive

• According to SVB, the deal decreases forecasted GAAP EPS by -12%, -7%, and -2% in 2023, 2024, and 2025 from that expected for standalone Merck.

• But, in the longer term, the positive impact on free cash flow (FCF) generation, top & bottom-line growth, and partial mitigation of Merck's Keytruda loss of exclusivity in 2028 are supportive of the deal.

• The analysts expect lower Keytruda revenue estimate dependence in 2028 to 42.5% from 48.4%.

• Further, a DCF analysis (2024-2032E) suggests that the combined entity could be worth $136/share (~$388 billion equity value). SVB forecasts Merck at $104/share.

• The combined entity can generate an estimated FCF of ~$247 billion from 2024 to 2032 versus around $176 billion for standalone Merck.

• But increasing debt costs, and decreasing equity values, could lead some investors to pause, despite the longer-term impact on FCF, SVB writes.

https://finance.yahoo.com/news/svb-leerinks-pro-forma-analysis-172506195.html

Roche Accelerator in Shanghai Helps Biotechs Expand Collaborations & Networks

 Biotech companies are hopping onto the Roche bandwagon and its China vision, as Roche opens the Roche Accelerator in Shanghai. Although Roche declined to comment on the number of companies signing on, at least two – METiS Therapeutics and SQZ Biotech – have publicly announced their participation in this new accelerator in China.

METiS, headquartered in Cambridge, Massachusetts, was among the first companies to join the Roche accelerator. Its reasons include “establishing a closer connection with a global leader in healthcare…and exploring deeper collaboration opportunities,” Chris Lai, Ph.D., co-founder and CEO, said when making the announcement.

METiS is developing an AI platform, AiTEM, to enable more efficient candidate selection and formulation design, programmable nucleic acid drug development and delivery design. “AiTEM has completed its proof-of-concept studies and is being used by many collaborators, including multinational corporations,” Lai told BioSpace. It also is developing an AiTLNP platform to support companies developing lipid nanoparticles for gene and RNA therapeutics, such as mRNA vaccines, siRNA and CRISPR therapeutics.

As part of the accelerator, “METiS hopes to support Roche in transforming the efficiency of small molecule formulation development, enable delivery of gene and RNA therapeutics and co-develop a pipeline with Roche accelerator affiliates,” Lai said. That includes working with Roche and other Accelerator companies in the United States and European Union.

For METiS, it’s important to be in China as well as the rest of the world. “Being the first batch of members to the Roche Accelerator (Shanghai) brings METiS closer to top biotech companies in China,” Lai pointed out, thus expanding the potential for collaborations with leading companies there.

Importantly, the benefits flow both ways. Participation in the Roche Accelerator (Shanghai) will bring the top biotech companies closer to a cutting-edge AI platform designed specifically for biopharmaceutical development. As Lai said, “Our AiTEM platform helps Roche and the Accelerator companies bring formulations to the discovery phase. This enables an effective ‘lead + formulation’ optimization and improves probability of success of small molecule drugs.”

Likewise, SQZ Biotech, a cell therapy company headquartered in Watertown, MA, is collaborating with the Roche Accelerator to support early strategic planning and, possibly, China-based initiatives. As Armon Sharei, Ph.D., founder and CEO, told BioSpace, “China has significant patient needs across the disease areas where we are developing cell therapies. Our goal in China is to extend the mission of the company, which is to create a new generation of cell therapies that could enable transformative patient outcomes across disease areas while remaining safe and practical to administer.” As Roche has been a longstanding partner and has a long track record in China, it is a natural collaborator as SQZ extends its presence there through what it calls its China Initiative.

SQZ is developing its proprietary Cell Squeeze technology, which temporarily disrupts the cell membrane to open, thus allowing biological material of interest to diffuse into the cell. Therapies are in Phase I/II development for head and neck, cervical and anal cancers, along with early-stage programs for celiac disease, Type I diabetes and chronic hepatitis B.

 “Over the past few months, SQZ has shared its intent to provide external life sciences groups access to our exciting technology in both research and clinical manufacturing settings,” Sharei said. Its Cell Squeeze technology is relevant to the range of indications being pursued by Roche Accelerator companies, “including oncology, immunology, neuroscience, RNA therapy and cell therapy.”

Sharei said SQZ plans to house aspects of its China Initiative at the Roche Accelerator. “We envision a small team of locally-hired talent working at the Accelerator when it opens. Shanghai has a strong life sciences education and industry ecosystem that will support our recruitment efforts,” he pointed out. 

 The Shanghai team will collaborate with U.S.-based colleagues for cross-training and to enhance the development of ideas and solutions, Sharei said. “Through this exchange, we foresee developing a transpacific partnership mindset and a greater understanding of domestic needs and interests.”

 The Roche Accelerator is evidence of Roche’s continuing belief in the opportunities resulting from China’s scale, and its commitment to the biopharma industry and emerging innovation. “By 2030, China aims to be the leading healthcare market in the world, and our aspiration is for Roche to become a leading healthcare company in China,” the company said when introducing the Accelerator.

To that point, after the sixth plenary session of the 19th Communist Party of China Central Committee last autumn, Shanghai’s mayor called for additional support for the city’s biopharma cluster and efforts to enhance the industry’s development. Shanghai’s three-year plan includes increasing the annual industrial output of biopharmaceuticals by 33% (from 600 billion yuan to 800 billion yuan -- approximately $28 billion USD).

The Roche Accelerator (Shanghai) is just one of several incubators founded by Western companies. Ilumina partnered with Sequoia Capital to launch a genomics incubator in Shanghai in early 2021. Known as the “Sequoia Capital China Intelligent Healthcare Genomics Incubator, Powered by Illumina,” it offers at least $500,000 in funding for a few select companies, as well as lab space and access to expertise. A couple years earlier, in 2019, Johnson & Johnson Innovation’s JLABS opened an incubator in Shanghai. Like the Roche Accelerator, JLABS@Shanghai is located in Shanghai's Zhangjiang Hi-Tech Park. It currently accommodates 41 companies in its 4,400-meter facility. Merck KGaA’s Accelerator China is a six-month program that provides up to €50,000 funding and includes access to its Shanghai Innovation base and exposure to investors and business partners.

The Roche Accelerator is designed to help companies bridge the gap between idea and proof-of-concept. The 5,000 square meter (53,819 square foot) facility will house state-of-the-art laboratories, offices and collaboration spaces. “The Accelerator plans to offer shared support services to its members, including human resources systems, procurement systems, intellectual property and legal services,” Sharei added. “This may be helpful to us as we work to identify and secure talent, as well as manage daily business operations.”

https://www.biospace.com/article/roche-accelerator-in-shanghai-helps-biotechs-expand-collaborations-and-networks/