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Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced that all patients have been dosed with UX701 across the three dose-escalation cohorts in Stage 1 of its pivotal Phase 1/2/3 Cyprus²⁺ study. The company’s investigational AAV9 gene therapy is designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion, with the goal of normalizing copper metabolism in patients with Wilson disease.

“With the support of patients, physicians and the Wilson disease community, we’ve completed Stage 1 enrollment in the Cyprus²⁺ program, which moves us one step closer to beginning Stage 2, the pivotal, randomized placebo-controlled stage of the study,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “Beyond the seamless nature of this study, another important differentiator of this program is that it leverages our Pinnacle PCL™ platform, which enabled a single run to support Stage 1, demonstrating that the productivity improvements generated by our platform are able to support larger-scale clinical programs.”

Data presented in October 2023 at a Company Analyst Day demonstrated that UX701 has been well tolerated in the first dose cohort, with no unexpected related treatment emergent adverse events observed as of the data cut-off date. Four of five patients enrolled in Cohort 1 had started tapering standard-of-care treatment, including two that came completely off of chelators and/or zinc therapy. Additional interim data from all three Stage 1 dose cohorts are expected in the first half of 2024, which will be followed by dose selection and initiation of Stage 2 in the second half of 2024.

U.S. residents can learn more by visiting www.ultraclinicaltrials.com.

Phase 1/2/3 Cyprus²⁺ study design
This study evaluating UX701 for the potential treatment of Wilson disease is designed with three stages. During the first stage, the safety and efficacy of up to three dose levels of UX701 will be evaluated over the course of 52 weeks and a dose will be selected for further evaluation in Stage 2. In this first stage, 15 patients were enrolled into three sequential dosing cohorts to evaluate doses of 5.0 x 10^12 GC/kg, 1.0 x 10^13 GC/kg, and 2.0 x 10^13 GC/kg.

In Stage 2, a new cohort of patients will be randomized 2:1 to receive the selected dose of UX701 or placebo. The primary safety and efficacy analyses will be conducted at Week 52 of Stage 2. The primary efficacy endpoints are change in 24-hour urinary copper concentration and percent reduction in standard-of-care medication by Week 52. After the initial 52-week study period, all patients will have long-term follow up in Stage 3.

About Wilson Disease
Wilson disease is a rare inherited disorder caused by mutations in the ATP7B gene, which results in deficient production of ATP7B, a protein that transports copper. Loss of function of this copper-binding protein results in the accumulation of copper in the liver and other tissues, most notably the central nervous system, and failure to properly distribute copper by ceruloplasmin. Patients with Wilson disease experience hepatic, neurologic and/or psychiatric problems. Those with liver disease can experience such symptoms as fatigue, lack of appetite, abdominal pain and jaundice, and can progress to fibrosis, cirrhosis, life-threatening liver failure and death. Wilson disease can be treated by reducing copper absorption or removing excess copper from the body using life-long chelation therapy, but unmet needs exist because some treated patients experience clinical deterioration and severe side effects. Wilson disease affects more than 50,000 individuals in the developed world.

About UX701
UX701 is an investigational AAV9 gene therapy designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion. It has been shown in preclinical studies to normalize copper trafficking and excretion from the body. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to UX701.

About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

For more information on Ultragenyx, please visit the company’s website at: www.ultragenyx.com.

Ultragenyx Forward-Looking Statements and Use of Digital Media
Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx’s expectations and projections regarding its future operating results and financial performance, business plans and objectives for UX701, expectations regarding the tolerability and safety of UX701, and future clinical and regulatory developments for UX701, are forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the company to successfully develop UX701, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements.

For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 3, 2023, and its subsequent periodic reports filed with the SEC.

In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/).

https://www.globenewswire.com/news-release/2024/01/25/2817385/0/en/Ultragenyx-Announces-Completion-of-Dosing-Across-Stage-1-Cohorts-in-Pivotal-Phase-1-2-3-Cyprus2-Study-Evaluating-UX701-Gene-Therapy-for-the-Treatment-of-Wilson-Disease.html

Posted on LinkedIn, “Greg Sarris, chairman of the Federated Indians of Graton Rancheria, and SSU President Mike Lee cut the ribbon officially marking the opening of The Federated Indians of Graton Rancheria (FIGR) Learning Center at Fairfield Osborn Preserve on Tuesday, January 16. Sarris and Lee were joined by more than 50 elected officials, community members, and SSU faculty and staff to celebrate the Center, which doubled its capacity thanks to a $2.8-million gift from FIGR, and now can accommodate two groups simultaneously. At the core of the renovation is a Listening Area, a space dedicated to listening to both each other and the wisdom the environment has to offer.”

https://www.linkedin.com/posts/sonoma-state-university_greg-sarris-chairman-of-the-federated-indians-ugcPost-7153141994112827392-WqI5/?utm_source=share&utm_medium=member_android

Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today announced the completion of patient enrollment in its Phase 1/2 clinical trial of GTX-102 for the treatment of pediatric patients with Angelman syndrome (AS). The dose-expansion cohorts (Cohorts A-E) have enrolled 53 patients for a total of 74 patients enrolled globally in the Phase 1/2 trial. GTX-102 is an investigational antisense oligonucleotide delivered via intrathecal administration and is designed to target and inhibit expression of UBE3A antisense transcript (UBE3A-AS).

“With completion of enrollment in the Phase 1/2 trial, we remain on track to report results in the first half of 2024 from at least 20 expansion cohort patients on therapy for a minimum of 6 months. We are confident that the cumulative safety and efficacy data will allow for dose and endpoint selection to support our Phase 3 program,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “We appreciate the support of the Angelman community, including the patients, families and healthcare providers, as we urgently work together to develop a new treatment option that may be able to improve the quality of life of those impacted by this devastating disease.”

In October 2023, interim data from the extension cohorts (Cohorts 4-7) of the ongoing Phase 1/2 study were announced and showed improvements across multiple domains compared to natural history data, where available, and clinical changes were associated with quantitative changes in EEG. Long-term data showed patients who stopped and restarted treatment reacquired previously gained developmental skills when they were re-dosed with the current regimen. As of the data cut-off, there have been no additional treatment-related SAEs, including lower extremity weakness, since November 2022.

About the Phase 1/2 study

The Phase 1/2, open-label, multiple-dose, dose-escalating study is evaluating the safety and tolerability of GTX-102 administered by intrathecal (IT) injection to pediatric patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The study is also assessing clinical response as measured by a panel of efficacy assessments for the functional domains impacted in Angelman syndrome. Patients in the earlier extension cohorts (Cohorts 4-7) of the study have moved into long-term maintenance dosing, and the study has completed enrollment for the new expansion cohorts to verify the GTX-102 dose range and treatment regimen that will be used in the Phase 3 program.

About Angelman Syndrome

Angelman syndrome is a rare, neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. The maternal-specific inheritance pattern of Angelman syndrome is due to genomic imprinting of UBE3A in neurons of the central nervous system (CNS), a naturally occurring phenomenon in which the maternal UBE3A allele is expressed and the paternal UBE3A is not. Silencing of the paternal UBE3A allele is regulated by the UBE3A antisense transcript (UBE3A-AS), the intended target of GTX-102. In almost all cases of Angelman syndrome, the maternal UBE3A allele is either missing or mutated, resulting in limited to no protein expression. This condition is generally not inherited but instead occurs spontaneously. It is estimated to affect 1 in 12,000 to 1 in 20,000 people globally.

Individuals with Angelman syndrome have developmental delay, balance issues, motor impairment, and debilitating seizures. Some individuals with Angelman syndrome are unable to walk and most do not speak. Anxiety and disturbed sleep can be serious challenges in individuals with Angelman syndrome. While individuals with Angelman syndrome have a normal lifespan, they require continuous care and are unable to live independently. Angelman syndrome is not a degenerative disorder, but the loss of the UBE3A protein expression in neurons results in abnormal communications between neurons. Angelman syndrome is often misdiagnosed as autism or cerebral palsy. There are no currently approved therapies for Angelman syndrome; however, several symptoms of this disorder can be reversed in adult animal models of Angelman syndrome suggesting that improvement of symptoms can potentially be achieved at any age.

About GTX-102

GTX-102 is an investigational antisense oligonucleotide delivered via intrathecal administration and designed to target and inhibit expression of UBE3A-AS. Nonclinical studies show that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the CNS. Reactivation of paternal UBE3A expression in animal models of Angelman syndrome has been associated with improvements in some of the neurological symptoms associated with the condition. GTX-102 has been granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA.

Ultragenyx Forward-Looking Statements and Use of Digital Media

Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx’s expectations and projections regarding its future operating results and financial performance, future clinical and regulatory developments for GTX-102, the clinical benefit, tolerability and safety of GTX-102, timing for enrollment, dosing and data for GTX-102 and the company’s other investigational therapies and regulatory meetings are forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the company to successfully develop GTX-102, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to adverse side effects, risks related to reliance on third-party partners to conduct certain activities on the company’s behalf, the potential for any license or collaboration agreement, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the Company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and product candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements.

For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 3, 2023, and its subsequent periodic reports filed with the SEC.

In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/).

https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-completion-enrollment-global-phase-12-trial

While climate change is all around us, and the projections are uniformly grim, there have never been so many local, national and global opportunities to build a sustainable future. Flourishing Children, Healthy Communities and a Stronger Nation: The U.S. Early Years Climate Action Plan gathers the results of a year-long exploration of the implications of climate change for young children.

👉 Download the Early Years Climate Action Plan

The work began as a series of listening sessions that generated the ideas and perspectives in the Action Plan. “As heartbreaking as those stories were, it’s also inspiring to hear the creative solutions and practical ideas that emerged,” said Elizabeth Bechard, senior policy analyst at Moms Clean Air Force, during a virtual launch hosted by Capita’s Ankita Chachra.

Are you searching for inspiration? Here are seven encouraging highlights from the Action Plan:

1.The pandemic showed us how resourceful we can be. On the November 7 Hunt Institute webinar marking the Action Plan’s release, Diana Rauner—president of Start Early, and co-chair of the Early Years Climate Action Task Force—admitted that the planet is stressed and the solutions are underfunded but reminded participants that throughout history, partnerships arise during crises.

For example, the Action Plan describes how, in the wake of Hurricane Katrina, the Louisiana-based nonprofit Agenda for Children launched the Rebuild Child Care Collaborative, which pooled private funding for child care centers. In 2021, after Hurricane Ida, the Agenda and the Louisiana Policy Institute for Children jointly distributed over $720,000 to 382 child care centers and family child care providers.

The global Covid pandemic offered plentiful examples of communities banding together; in Louisiana, Agenda for Children facilitated case management and legal advice to help child care centers secure Paycheck Protection Program loans.

2.The child care workforce is finding its voice. According to the Bureau of Labor Statistics, just over 1 million people work in child care in America (far more, if you count all the unpaid labor), and this workforce is dedicated to protecting our nation’s children. At a luncheon discussion exploring the Action Plan held by Capita and the Aspen Institute in Washington, D.C., Melissa Rooker of the Kansas Children’s Cabinet and Trust Fund described child care workers as first responders, and the Action Plan spotlights North Bay Children’s Center, a California child care network with 13 locations that tracked the movements of children and families in the aftermath of the 2017 wildfires, linking them to emergency food and other resources.

“During the climate-related disasters that we’ve experienced over the past several years,” said North Bay’s Susan Gilmore, “The child care industry needs to be seen as essential, and like school districts, child care representatives should be included in the organizational structure of each county’s emergency operations center.”

During the Hunt Institute webinar, Erica Phillips, executive director of the National Association for Family Child Care, said, “While our sector is incredibly diverse, we are here to be allies in the climate planning work.”

3.The business community is engaged. The climate crisis that the experts have long predicted? It’s here. During the virtual launch, Angie Garling of the Low Income Investment Fund recalled a 106° F day in California’s Coachella Valley when the children were kept inside for their own safety.

As Antwanye Ford—president & CEO at Enlightened, Inc., and co-chair of the Early Years Climate Action Task Force—quipped at the Capita-Aspen luncheon, “Long-term becomes now really fast.”

The Action Plan singles out the Greater Seattle Child Care Business Coalition for recognizing the urgency; it supports child care providers by creating opportunities for them to learn about topics like employment law grants management. The coalition seeks greater investments from government and business and has amplified warnings about the impact of extreme heat.

Across the nation, the Inflation Reduction Act is incentivizing green energy solutions, and some observers predict the private sector will undertake even more substantial climate investments of its own accord.

The Action Plan recommends the creation of climate-aware policies and programs for employees with young children, fostering partnerships between businesses and early years facilities to fund essential upgrades, as well as partnering with local communities to build climate-resilient green space and community infrastructure.

4.Government is taking action. While the climate dimensions of the Inflation Reduction Act have received more attention, it is far from the only effort worth noting. In a conversation with Capita’s Joe Waters, Rep. Jennifer McClellan of Virginia, outlined the benefits of the bipartisan Child Care Assistance for Maternal Health Act, which would increase short-term child care access during pregnancy, birth and the postpartum period. (Climate change adversely impacts pregnancy health directly and indirectly.)

Politics also follows public opinion, and sentiment toward climate action is increasing: Three out of four Americans feel they have a “moral obligation” to make the world a better place by addressing climate change not only for their own children and grandchildren but for all children to come. Many state and local governments are recognizing that steps to protect the youngest residents from climate catastrophe are necessary and possible.

At the state level, Action Plan recommendations include the creation of climate leadership roles and breaking down silos through collaborative structures. For example, California’s Child Care and Development Infrastructure Grant Program prioritizes the installation of energy-efficient electric appliances and retrofitting for disaster mitigation. At the local level, the Action Plan cites the work of Climate Mayors and recommends “integrating the perspectives of young children, their families and those who support them.”

During the Hunt Institute webinar, Dr. Rauner demonstrated a line of questioning for conversations with local officials: “What if we looked at our development from the perspective of a smaller person?”

5.Philanthropy is having an impact. U.S. foundations grant more than $105 billion annually, and a recent survey of 188 foundation executives found that more than 60% are funding efforts to address climate change. (Still others are focused on equity, and during the Hunt Institute webinar, Elliot Haspel, senior fellow at Capita—and Early Learning Nation columnist—memorably referred to climate change as an inequity multiplier.)

As impressive as these figures are, there is clearly room to expand these investments and to target them toward efforts that benefit young children and families. The Action Plan’s recommendations for the philanthropic sector include funding work that connects early years and climate change; developing a regular national scorecard on the state of young children and climate change; and supporting communities in efforts that promote healthy development for young children in a changing climate.

6.Children are vulnerable, but they’re also resilient. The word resilience can be a double-edged sword, both complementing people from disinvested communities for their innate strengths and expecting them to bounce back from every hardship and disaster. The Action Plan uses the word 88 times over its 99 pages, referring to climate resilience as well as the children whose future depends on it (see sidebar).

At the Capita-Aspen luncheon, Robert Mayer, KABOOM’s associate director for Public Policy and Advocacy, made the comment that the most subsequent speakers quoted: “Children will be as adaptive as society allows them to be.”

7.The Action Plan is just the start. As Capita and its partner organizations communicate the Plan’s findings and recommendations, the hope is that the dialogue will proliferate wherever decision makers, advocates and activists gather to envision the future—taking inspiration from those with lived experience. “People from disadvantaged communities are already showing the way,” said Haspel at the Capita-Aspen luncheon.

There’s also a lot to learn about adaptation from indigenous communities. During the virtual launch, Alicia Mousseau, vice president of the Oglala Sioux Tribe, noted, “Tribal communities have always adapted to things that we’ve never experienced before in our history.”

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Two Types of Resilience

“Climate resilience is the capability to anticipate, prepare for, respond to and recover from significant multi-hazard climate threats with minimum damage to social well-being, the economy and the environment.”

“Resilience (distinct from climate resilience) refers to the ability to overcome serious hardship. Children’s resilience is the result of a combination of protective factors. Neither individual characteristics nor social environments alone are likely to ensure positive outcomes for children who experience prolonged periods of toxic stress. Children build resilience via an interaction between biology and the environments in which they live.”

Basin Street Properties, a prominent norther California and northern Nevada real estate investment, development, and management firm is pleased to announce a successful 2023 for office leasing.  Across its three markets (Reno, Sacramento, and North Bay) Basin Street completed 76 new leases totaling 294,408 square feet and 124 renewals totaling 444,150 square feet.   Basin Street maintained 89% occupancy across its portfolio.

“The leasing activity by new and existing tenants indicates their attitudes towards the economy and their office needs,” said Scott Stanzl, Chief Portfolio Office at Basin Street Properties. “Businesses continue to see the benefits of a Class A office for productive teams and attracting and retaining clients.”

In the North Bay, Basin Street signed 35 new leases for 129,622 square feet and 76 renewals for 244,828 square feet in 2023. We signed new leases with Santa Rosa School District, Muir Wood and Bay Alarm taking 28,067 square feet. Basin Street also renewed CamelBak, Abbey, Weitzenberg, Warren & Emery and National Instruments for a total of 58,558 square feet.

“We succeeded in attracting tenants moving to quality as they evolve with hybrid work arrangements and right size to smaller spaces,” said Stranzl. “Businesses desire quality space and amenities like fitness centers, conference rooms, concierge service and cafes to optimize the office experience and draw team members back to the office.”

In Sacramento, Basin Street signed 29 new leases totaling 114,045 square feet and 31 renewals for 123,372 square feet. New leases with Pacific Charter Institute, Samsung Electronics and Gannett Fleming totaled 30,646 square feet. We also renewed Ameriprise Financial, TY Lin and Blackrock for a total of 23,640 square feet.

In Reno, Basin Street executed 12 new leases for 50,742 square feet and 17 renewals for 75,950 square feet. New leases with NCE Engineering, DL Freight Solutions and City of Reno totaled 23,701 square feet. Basin Street renewed and expanded Kaempfer Crowell from 7,340 square feet to 16,319 square feet and renewed Clear Capital and Northern Nevada Bath for a total of 35,097 square feet.

Basin Street expects this momentum to continue in 2024.  Interest rate hikes have plateaued, and we anticipate achieving the soft landing we hoped for with the economy.  We have positioned our properties to attract rightsizing new tenants and our team works hard to maintain high satisfaction with our existing tenants.

We are grateful for our hardworking brokers, property managers, engineers and many other team members and vendors across our markets keeping our properties looking great and helping our tenants succeed.

 

ABOUT BASIN STREET PROPERTIES:

Basin Street Properties, established in Petaluma in 1974, is one of Northern California’s and Northern Nevada’s most prominent developers, investors and managers of commercial properties. The company owns and manages over 5 million square feet of Class A office space. Basin Street is widely recognized for its office, retail, hospitality, multi-family and mixed-use developments. The company offers a broad range of real estate services, including development, leasing, property management, construction management, financial and asset management, and property acquisition and disposition. For more information, visit basin-street.com.

Media Contact:

Mike Williams
mwilliams@basin-street.com
530.448.1986