Krystal Biotech Launches Spinoff for Gene-Based Anti-Wrinkle Products

 On the back of a $135 million public offering in February, rare disease gene therapy company Krystal Biotech has launched subsidiary Jeune Inc. to promote its gene therapies for aesthetic skin conditions.

In conjunction with the launch, Jeune announced positive initial Phase I safety data for KB301, now its lead asset. The company said no safety signals or serious adverse events were observed in seven healthy subjects.

Jeune is planning to move KB301 efficacy cohorts later this year in patients with wrinkles and acne scars.

Several other companies–including Pittsburgh-based parent Krystal–are exploring gene therapies for more serious or life-threatening skin diseases like epidermolysis bullosa. Krystal, Castle Creek Biosciences, and Abeona Therapeutics all have gene therapies delivering the COL7A1 gene in Phase III testing for patients with dystrophic epidermolysis bullosa (EB).

Defective COL7A1 prevents healthy production of type VII collagen in these patients, and severe dystrophic EB can be fatal. Castle Creek and Abeona are testing their therapies in patients with the more severe recessive dystrophic EB, while Krystal’s B-VEC is in patients with either recessive or dominant forms.

But Jeune’s KB301 delivers a full-length COL3A1 gene to promote type III collagen synthesis, which is reduced in aged skin. Like Krystal’s other gene therapies in development, KB301 is delivered via an HSV-1 vector, which the company says makes the therapies redosable, if needed.

The PEARL-1 trial, launched last August, is an open-label study enrolling adults up to 75 years old, and the efficacy arms will enroll up to 22 patients with either shallow-to-moderately deep facial wrinkles or moderate-to-severe atrophic acne scars. In the safety arm, transient adverse events were limited to mild-to-moderate injection or biopsy site reactions. The company plans to present additional data during a virtual poster presentation at the Society for Investigative Dermatology (SID) Annual Meeting in May.

Although Jeune is focused on aesthetic skin conditions, the U.S. Food and Drug Administration (FDA) has said that a product designed to remove wrinkles or increase skin collagen production in the skin would be regulated as a drug. There are no other known clinical trials ongoing for a type III collagen-based therapy.

Bhusan Hardas, an industry veteran who was previously chief medical officer of Allergan's Dermatology and Medical Aesthetics business, will begin as president of Jeune later this month.

Jeune is a wholly-owned subsidiary of Krystal. No financial details about Jeune have been disclosed.

https://www.biospace.com/article/krystal-biotech-launches-spinoff-for-gene-based-anti-wrinkle-products/

Ikena Oncology sets terms for $125 million IPO

 Ikena Oncology, a Phase 1 oncology biotech developing small molecule inhibitor therapies, announced terms for its IPO on Monday.

The Boston, MA-based company plans to raise $125 million by offering 7.8 million shares at a price range of $15 to $17. At the midpoint of the proposed range, Ikena Oncology would command a fully diluted market value of $606 million.

Ikena Oncology is a targeted oncology company focused on developing novel cancer therapies targeting key signaling pathways that drive the formation and spread of cancer. Its lead targeted oncology candidate, IK-930, is an oral small molecule inhibitor of the TEAD transcription factor in the Hippo signaling pathway, and the company intends to submit an IND for IK-930 in the 2H21. Ikena is also developing candidates designed to modulate the tumor microenvironment in specific patient populations, with its two most advanced candidates currently being evaluated in Phase 1 trials.

Ikena Oncology was founded in 2016 and booked $9 million in revenue for the 12 months ended December 31, 2020. It plans to list on the Nasdaq under the symbol IKNA. Jefferies, Cowen, Credit Suisse and William Blair are the joint bookrunners on the deal.

Relevant Profile: IKNA

https://www.renaissancecapital.com/IPO-Center/News/79776/Oncology-biotech-Ikena-Oncology-sets-terms-for-$125-million-IPO

Pandemic spurs Canada to offer path to citizenship to more temporary residents

 Canada’s recent move to offer permanent residency to more foreigners living and working in the country is a short-term solution to the economic problems spurred by a pandemic-related immigration slowdown, analysts say, while critics argue the strategy excludes too many vulnerable people.

With travel restrictions in place, visa offices closed and immigration applications stalled, the Canadian government finds itself on the back foot as it attempts to reach its target of attracting a record 401,000 new permanent residents in 2021.

The country, which admitted 184,370 people in that category last year, the lowest number since 1998, is turning its attention to the more than 1 million temporary residents within its borders to boost the numbers, inviting some to apply for permanent residency.

Economists, however, say the move will not have a noticeable impact on Canada’s economic growth and is not a fix to the country’s long-term demographic challenges, including an aging population.

“In the short-term, it’s nice that they’re targeting these sorts of people. It’s really just a change of status,” said Andrew Agopsowicz, a senior economist at the Royal Bank of Canada.

Without any immigration, Canada’s average annual rate of economic growth by 2034 would shrink by 0.6 percentage points, the Conference Board of Canada said in 2018.

Canadian Immigration Minister Marco Mendicino told Reuters in an interview last week that the limitations posed by the pandemic mean “we need to look at the talent pool that is already within our borders.”

In January, Canada welcomed 26,600 new permanent residents, most of whom were already in the country. That was 10% more than in the same period a year ago. Last month, the Canadian government invited 27,000 temporary workers who met certain conditions to apply for permanent residency. 

‘NOT A BOTTOMLESS WELL’

Mendicino said January’s numbers indicate the country can meet its 2021 target, but others disagree.

“We might still end up seeing a slowdown heading into the spring and summer. ... There is a large temporary pool and it’s something Canada can draw from, but it’s not a bottomless well,” Agopsowicz said.

Canada has relied for decades on temporary workers to help meet the needs of its labor market. There have been pathways for these people to remain in the country, but they have tended to be narrow.

Mendicino argues the push to boost the numbers of permanent residents by drawing on temporary ones is more than cosmetic.

“The real benefits are derived once they put roots down and become more established in these jobs.”

The emergence of COVID-19 revealed gaps in Canada’s immigration system when it came to temporary residents who are uniquely exploitable but also essential, said Harald Bauder, a professor at Ryerson University in Toronto.

A path to permanent residency for them is needed, he added.

Mendicino said Canada may offer such a path for agricultural workers, who are frequently marginalized or excluded from such routes to immigration.

Some critics argue the government’s actions don’t safeguard vulnerable workers who are often employed in high-risk, low-wage jobs with little protection from such things as a pandemic and who tend not to qualify for permanent residency programs.

“The actual system, or the path to PR (permanent residency), hasn’t changed,” said Syed Hussan, executive director of the Migrant Workers Alliance for Change.

Canada will rely on its current strategy “certainly” through 2021 and 2022, said Mendicino, adding that the focus on turning temporary residents into permanent members of Canadian society could signal a long-term shift.

Others are more skeptical.

“Probably that pandemic blip is going to be a blip,” said Arthur Sweetman, an economist at McMaster University in Hamilton, Ontario. “I think it’s going to last as long as the borders are closed.”

https://www.reuters.com/article/us-health-coronavirus-canada-immigration/analysis-pandemic-spurs-canada-to-offer-path-to-citizenship-to-more-temporary-residents-idUSKBN2AW1BJ

Design Therapeutics Announces Pricing of IPO

 Design Therapeutics, Inc., a biotechnology company developing a platform of gene targeted chimera (GeneTAC™) small molecules for the treatment of serious degenerative disorders caused by inherited nucleotide repeat expansions, today announced the pricing of its initial public offering of 12,000,000 shares of its common stock at a price to the public of $20.00 per share. The gross proceeds to Design from the offering, before deducting the underwriting discounts and commissions and offering expenses, are expected to be $240.0 million. All of the shares are being offered by Design. In addition, Design has granted the underwriters a 30-day option to purchase up to an additional 1,800,000 shares of its common stock at the initial public offering price less the underwriting discounts and commissions.

The shares are expected to begin trading on the Nasdaq Global Select Market on March 26, 2021, under the ticker symbol “DSGN.” The offering is expected to close on March 30, 2021, subject to the satisfaction of customary closing conditions.

Goldman Sachs & Co. LLC, SVB Leerink LLC and Piper Sandler are acting as joint book-running managers for the offering.

https://www.globenewswire.com/news-release/2021/03/26/2199816/0/en/Design-Therapeutics-Announces-Pricing-of-Initial-Public-Offering.html

Cholesterol may be key to new therapies for Alzheimer's, diabetes

 A University of Arizona Health Sciences researcher examined the role of cholesterol in both Alzheimer's disease and Type 2 diabetes to identify a small molecule that may help regulate cholesterol levels in the brain, making it a potential new therapeutic target for Alzheimer's disease.

There is no known cure for Alzheimer's disease, which affects more than 5.5 million people in the United States. In the last decade, scientists have found increasing evidence linking the underlying causes of Type 2 diabetes and Alzheimer's disease.

Type 2 diabetes occurs when insulin becomes less efficient at removing glucose from the bloodstream, resulting in high blood sugar that can cause abnormal cholesterol levels. A similar situation occurs in Alzheimer's disease, but rather than affecting the body as a whole, the effects are localized in the brain.

"Alzheimer's and diabetes share many common causes," said Gregory Thatcher, Ph.D., professor of pharmacology and toxicology in the UArizona College of Pharmacy and the newly named R. Ken and Donna Coit Endowed Chair in Drug Discovery. "Our goal was to develop a way of identifying compounds that would counteract many detrimental changes that contribute to both Alzheimer's and Type 2 diabetes."

The paper, "Discovery of Nonlipogenic ABCA1 Inducing Compounds with Potential in Alzheimer's Disease and Type 2 Diabetes," was published in the journal ACS Pharmacology and Translational Science.

When cholesterol rises, due to insulin resistence or other factors, the body starts a process known as reverse cholestrol transport, during which specific molecules carry excess cholesterol to the liver to be excreted. Apolipoprotein E (APOE) is one of the proteins involved in reverse cholesterol transport.

APOE is also the strongest risk factor gene for Alzheimer's disease and related dementia, and an independent risk factor for Type 2 diabetes and cardiovascular disease. Similarly, reduced activity of another cholesterol transporter, ATP-binding cassette transporter A1 (ABCA1), correlates with increased risk of cardiovascular disease, Type 2 diabetes and Alzheimer's disease.

"While most people are aware of so-called 'good cholesterol,' and 'bad cholesterol,' associated with risk of heart attack and stroke, these broad concepts are also applicable to a healthy brain," said Dr. Thatcher, who has been working to develop advanced therapeutics for Alzheimer's for more than 20 years. "Moving cholesterol to where it is needed in the body has positive effects on many physiological processes and can help clear misfolded proteins that accumulate in the brain."

Increasing the activity of ABCA1 is expected to positively influence insulin signaling and reduce inflammation in the brain, making it a potential therapy for both Type 2 diabetes and Alzheimer's disease. In this study, Dr. Thatcher and the research team designed a way to identify small molecules that improve the function of ABCA1 in the body while avoiding unwanted effects to the liver.

In a March 20 paper in the journal EBioMedicine, "Metabolomic analysis of a selective ABCA1 inducer in obesogenic challenge provides a rationale for therapeutic development," Dr. Thatcher's team honed in on a specific small molecule, CL2-57, due to its ability to stimulate ABCA1 activity with positive effects on liver and plasma triglycerides. The use of this compound showed improved glucose tolerance and insulin sensitivity, as well as reduced weight gain, among other beneficial effects.

Their future research will seek to improve the properties of the small molecules to increase the levels in the brain. Their long-term goal is to understand which patients suffering from the cognitive and neuropsychiatric symptoms of Alzheimer's and dementia will benefit from the treatment.

"During the COVID-19 pandemic we hear about the mounting deaths in nursing homes and it's important to remember that Alzheimer's and related dementia is a major cause of the elderly moving to nursing homes," Dr. Thatcher said. "It would be good to think of a future in which healthspan was extended, especially a healthy brain; maybe that's more important than lifespan."

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Potential target for diabetes-associated Alzheimer's disease

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More information: Manel Ben Aissa et al, Discovery of Nonlipogenic ABCA1 Inducing Compounds with Potential in Alzheimer's Disease and Type 2 Diabetes, ACS Pharmacology & Translational Science (2021). DOI: 10.1021/acsptsci.0c00149

https://medicalxpress.com/news/2021-03-cholesterol-key-therapies-alzheimer-disease.html

New discoveries about deep brain simulation put it on par with therapeutics

 Despite having remarkable utility in treating movement disorders such as Parkinson's disease, deep brain stimulation (DBS) has confounded researchers, with a general lack of understanding of why it works at some frequencies and does not at others. Now a University of Houston biomedical engineer is presenting evidence in Nature Communications Biology that electrical stimulation of the brain at higher frequencies (>100Hz) induces resonating waveforms which can successfully recalibrate dysfunctional circuits causing movement symptoms.

"We investigated the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson's disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130-180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment," reports Nuri Ince, associate professor of biomedical engineering.

For the past couple of decades, deep brain stimulation (DBS) has been the most important therapeutic advancement in the treatment of Parkinson's disease, a progressive nervous system disorder that affects movement in 10 million people worldwide. In DBS, electrodes are surgically implanted in the deep brain and electrical pulses are delivered at certain rates to control tremors and other disabling motor signs associated with the disease.

Until now, the process to find the correct frequency has been time consuming, with it taking sometimes months to implant devices and test their abilities in patients, in a largely back and forth process. Ince's method may speed the time to almost immediate for the programming of devices at correct frequencies.

"For the first time, we stimulated the brain and while doing that we recorded the response of the brain waves at the same time, and this has been a limitation over the past years. When you stimulate with electrical pulses, they generate large amplitude artifacts, masking the neural response. With our signal processing methods, we were able to get rid of the noise and clean it up," said Ince. "If you know why certain frequencies are working, then you can adjust the stimulation frequencies on a subject-specific basis, making therapy more personalized."

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Smart brain stimulators: Next-gen parkinson's disease therapy

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More information: Musa Ozturk et al. Electroceutically induced subthalamic high-frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson's disease, Communications Biology (2021). DOI: 10.1038/s42003-021-01915-7

https://medicalxpress.com/news/2021-03-discoveries-deep-brain-simulation-par.html

NYC to Set Up Vaccination Centers For Broadway Workers, Hoping To Raise Curtains This Fall

 

March 12th, 2020, the first night of Broadway going dark GRETCHEN ROBINETTE / GOTHAMIST

Over the next four weeks, New York City plans to set up COVID-19 vaccination sites specifically for Broadway theater workers, Mayor Bill de Blasio announced at a press briefing on Thursday, adding that he hopes to reach off-Broadway workers as well.

"We have to get the theater community ready for the fall," de Blasio said. "By the time we get there, the world will be better."

A mobile vaccination unit will also be deployed to accelerate the process, the mayor said.

Broadway shut down in mid-March last year. At the time there were 31 musicals and plays open, including several that were set to open that week. In February, a new report from the New York State Comptroller's office showed the devastating toll that the shutdown had on Broadway, as well as the entire New York City creative sector.

The mayor also announced today that the city plans to open COVID testing sites near theaters, and will set more detailed guidelines for handling crowds before and after shows. But he noted that actually opening Broadway theaters with these proposed safety measures still requires the approval of New York state.

"We will propose our own ideas to the state, but we need them to take action," he said. "To put together a Broadway show is a huge endeavor, so they need guidance now."

Under current state guidelines, theaters are now technically allowed to be open at 33% capacity, with a maximum of 150 people who've presented negative COVID-19 tests. But Broadway producers don't expect to return until sometime after Labor Day.

"Even if we got to 33%, we could not keep the show open for even a week," Charlotte St. Martin, the president of the Broadway League, told Gothamist. "The financial model for Broadway does not allow it."

To allow shows to at least prepare for reopening — a process that includes everything from rehearsals and costume fittings to marketing campaigns and ticket promotions — access to vaccines is seen as a crucial first step.

"New York is on its way back, but it will not completely arrive until Broadway and all theatre across the city returns," said Tony-winning actor Andre DeSheilds. "We want everyone to experience the ecstasy of a Broadway show."

https://gothamist.com/arts-entertainment/nyc-will-set-vaccination-centers-broadway-workers-hopes-raise-curtains-fall