Craniofacial Dysostosis

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Quiver Bioscience (“Quiver”), a discovery technology and therapeutics company advancing programs for the treatment of serious central nervous system (CNS) disorders, announces today a collaboration with the Dup15q Alliance to advance an antisense oligonucleotide (ASO) therapeutic program for chromosome 15q duplication (Dup15q) syndrome using Quiver’s innovative “Genomic Positioning System” (GPS). There are currently no disease-modifying treatments for Dup15q, which remains a substantial unmet medical need. Dup15q is a neurodevelopmental disorder characterized by moderate-to-severe hypotonia, motor and language delays, intellectual disability, epilepsy, and autism spectrum disorder (ASD). Most Dup15q individuals experience seizures and are at an increased risk for sudden unexpected death in epilepsy (SUDEP). Dup15q is associated with genomic copy number variations that result in increased levels of the UBE3A gene product. Dup15q syndrome is clinically related to Angelman syndrome (AS), a distinct neurodevelopmental disorder caused by UBE3A loss of function. ASO therapeutics for AS are currently in clinical trials and have shown early potential benefits in disease modification. The current prevalence estimates for Dup15q syndrome are as high as 1 in 4,000 live births. Genetic medicine approaches, such as ASOs, to reduce UBE3A levels are a viable precision therapeutic path for the treatment of Dup15q and have disease-modifying potential. Quiver has leveraged its unique GPS platform, which integrates unique-in-world, scalable, human single-cell neuronal electrophysiology data with artificial intelligence and machine learning (AI/ML) analytics, and extensive experience in ASO design to robustly model Dup15q syndrome and identify, optimize, and advance effective ASO candidates capable of reducing UBE3A and rescuing associated human Dup15q patient-specific cellular phenotypes. This initial grant formalizes a growing partnership between Quiver and the Dup15q Alliance that has been built over several years. The grant will support requisite preclinical studies to characterize Quiver’s lead therapeutic candidate ASOs and advance towards a transformative treatment for the Dup15q community. “We’re thrilled to continue working shoulder to shoulder with the excellent team at the Dup15q Alliance in advancing this important therapeutic for the community of patients and their families,” says Graham Dempsey, Ph.D., Founder and Chief Scientific Officer at Quiver Bioscience. “This is a devastating disease,” says Mike Porath, Executive Director of the Dup15q Alliance. “We are committed to developing a therapeutic treatment so people with Dup15q syndrome can thrive. We're excited to partner with Quiver to reach our ambitious goals as quickly as possible.” About Quiver Bioscience Quiver Bioscience is a technology-driven company established to create transformational medicines for the brain while simultaneously uncovering new biology and novel, effective drug targets. Using advanced single-cell imaging and multi-omics, we are building the world's most information-rich neuronal insight map via our "Genomic Positioning System". Our approach integrates cutting-edge scalable human models, state-of-the-art technology and proprietary engineering, and learning and surrogate AI/ML models to identify novel therapeutic targets and the best candidate molecules to deliver new and meaningful therapeutics to patients. For information, including additional publications describing the application of Quiver’s GPS to drug discovery, visit www.quiverbioscience.com. About Dup15q Alliance The Dup15q Alliance is a nonprofit organization devoted to bringing awareness to Dup15q syndrome and empowering individuals living with the condition by supporting scientific and clinical research towards effective therapeutics. Media: Noélle Germain +1-617-396-3611 noelle.germain@quiverbioscience.com ‍

Johnson & Johnson and Legend Biotech's additional investment comes just as the so-called Tech Lane facility is set to begin clinical production of Carvykti in a few weeks. On track to meet their long-stated capacity goal for multiple myeloma therapy Carvykti in 2025, Johnson & Johnson and Legend Biotech are already planning the next phase of their cell therapy manufacturing expansion.Based on internal projections for demand, the two companies have approved about $150 million in additional investments to expand the future capacity of a brand-new facility in Ghent, Belgium, Legend CEO Ying Huang, Ph.D., and interim Chief Financial Officer Jessie Yeung said on an investor call Tuesday.J&J and Legend decided on the new investment just as the so-called Tech Lane facility is set to begin clinical production of Carvykti in a few weeks. The site is expected to gain approval to initiate commercial supply by the end of 2025, according to Huang.For the latest expansion, early engineering and design work has begun, and construction is slated to start in the second half of 2025 and expected to be complete in 2028, Yeung said. The addition will primarily provide supplies for the EU market, a Legend spokesperson told Fierce Pharma.Over the last several years, J&J and Legend have been busy working to ramp up their cell therapy manufacturing capacity. Since Carvykti’s initial FDA approval in early 2022, supply constraints have limited the CAR-T therapy’s revenue growth. What’s more, an expanded FDA nod in April 2024 in second-line multiple myeloma roughly tripled the med’s eligible patient population.In one of the pair’s recent efforts to boost supply, contract manufacturer Novartis recently won FDA approval to make commercial supply of Carvykti at its site in Morris Plains, New Jersey, Huang said on the call. Also in New Jersey, J&J and Legend said in the fall of 2022 that they would double the investment in their flagship Raritan manufacturing facility to a total of $500 million. Legend now expects regulatory approval of a new section at that site in the second half of this year.The companies have another site in Ghent, called the Obelisc facility, which began commercial production in the third quarter of 2024 and is now operating at full capacity, according to Legend.These recent expansions will help the companies reach a capacity to be able to produce 10,000 doses of Carvykti on an annualized basis this year, a goal that was outlined in 2023.“By the end of this year, we’ll be in a situation where supply is fully meeting the demand where we are, and then we’ll be able to keep pace,” Alan Bash, Legend’s president of Carvykti, said on Tuesday’s call. But as analysts noted on the call, Wall Street’s 2026 consensus sales projection for Carvykti indicates that market watchers were unsure about whether patient demand will start to taper off.As of Tuesday, Carvykti can be administered at 104 certified treatment centers in the U.S. Meanwhile, growing levels of administration in the outpatient setting—and increased use at community practices—offer “significant upside” to the drug's growth trajectory, Bash said.Recipients of CAR-T therapies need to be monitored for the potentially life-threatening side effect of cytokine release syndrome. Because of Carvykti’s delayed onset of te syndrome, community providers are able to utilize outpatient administration, thereby freeing up limited inpatient space.This factor can help increase overall treatment capacity and therefore boost demand. The proportion of outpatient Carvykti use has increased from about 30% a year ago to more than 50% today, according to Bash.J&J and Legend have a three-stage plan to increase adoption in the community setting, where most multiple myeloma patients are treated. Right now, the drugmakers are reaching out to more than 8,000 community oncologists to educate them on Carvykti and to help them refer patients to certified treatment centers.In the second stage, starting later this year, the pair will identify certain regional hospitals and community accounts that are closely affiliated with large hospitals to administer Carvykti on-site, Bash said. For the third stage, which will begin next year, the goal is to have the drug more widely administered in community oncology practices, he added. Looming competition Another key reason analysts have reservations about Carvykti in 2026 is the expected entry of Gilead Sciences and Arcellx’s rival BCMA CAR-T anito-cel. In a pivotal phase 2 trial in late-line myeloma, anito-cel showed what analysts viewed as competitive efficacy and better safety to Carvykti, with the important caveat that cross-trial comparisons carry inherent flaws.On Tuesday’s call, Huang played down the potential threat of anito-cel for Carvykti in 2026. When approved, anito-cel would be entering the late-line setting, whereas the majority of Carvykti’s revenue mix will come from earlier lines, he argued. By the end of 2025, Legend expects about two-thirds to three-quarters of Carvykti revenue will come from second- to fourth-line treatment, he said.In anito-cel's phase 2 trial, one factor that stood out for the drug was the absence of some delayed neurotoxicities, including Parkinsonism, which has recently emerged as a concern for Carvykti. During Tuesday’s call, Legend executives pointed to a recent single-site study by the Colorado Blood Cancer Institute. The small study of 39 patients suggested that unrestrained absolute lymphocyte count (ALC) expansion is predictable of neurotoxicites following Carvykti treatment and that prophylactic treatment with the steroid dexamethasone may be able to mitigate the effect. The study did not separate delayed neurotoxocities from other neurologic complications.Legend is talking to multiple centers to potentially study this phenomenon in an investigator-initiated trial, and it has incorporated the mitigation strategy into ongoing Cartitude trial programs for Carvykti, Chief Medical Officer Mythili Koneru, M.D., Ph.D., said on Tuesday’s call.As to the real world, Koneru noted that an ALC-based monitoring and mitigation strategy is easily applicable, because it’s “a very typical lab result that is checked very frequently and commonly at all centers, including academic centers as well as in a community setting.”

NEW YORK--( BUSINESS WIRE )--OS Therapies, Inc. (NYSE-A: OSTX), a clinical-stage biotechnology company advancing immunotherapies and targeted drug conjugates for cancer treatment, today provided a corporate update to the marketplace to contextualize recent positive clinical data, corporate and financial developments. “January 2025 was the most significant month in the Company’s history,” said Paul Romness, MHP, Chairman & CEO of OS Therapies. “We started OS Therapies because someone very close to my family developed osteosarcoma and we realized that if first line therapy failed, the metastasis that could follow had very poor long-term prognosis. The data we generated in our Phase 2b trial with OST-HER2 provides the first glimmer of hope in over 40 years that a paradigm shift could radically change the course of this deadly disease. We intend to stay laser focused on our mission of bringing this therapy to market so that when the next family that gets the devastating news of an osteosarcoma diagnosis, they’ll know that treatment options might exist in the event that chemotherapy and resection/amputation fail to prevent metastasis, which is the case in approximately 50% of patients.” Cash position and burn rate On January 14, 2025, the Company disclosed that it completed a $7.1 million financing round (the “Preferred Round”) designed to fund the Company through a Biologics Licensing Authorization (BLA) decision from the US Food & Drug Administration (“FDA”) regarding the OST-HER2 program in the prevention of metastases in osteosarcoma. This was in addition to the $6 million initial public offering the Company completed in August 2024. Taken together, this $13.1 million that the Company raised over the last 6 months provides sufficient capital to fund: Final payments for the OST-HER2 osteosarcoma trial (inclusive of any expected non-clinical work required by FDA). Commercial manufacturing required for FDA approval and product launch. Strategic & operational costs related to FDA & EMEA correspondence, meetings, and regulatory submissions. Commercial launch preparations. Acquisition of the Listeria monocytogenes (“ Listeria ”) platform from Ayala. Corporate overhead. Under the terms of the Preferred Round, the Company is precluded from raising additional capital for 6 months, in addition to being precluded from selling shares under its Equity Line of Credit (“ELOC”) so long as the price of the common stock is below $12.00. Additionally, the warrants issued in connection with the Preferred Round have certain forced exercise provisions when the common stock trades above $12.00. An additional condition of the Preferred Round was the appointment of Mr. Karim Galzahr as a new member of the Company’s Board of Directors to help the Company navigate towards value creation for shareholders. The Preferred Round was funded over 90% by pre-IPO and IPO investors of the Company, including leading funders from the osteosarcoma community. As a result of the significant investment made to help advance OS Therapies’ mission, certain investors are now considered affiliates of the Company by virtue of owning at least 10% of the common shares. It is important to note that while this significant ownership entitles the investors to representation, it also binds them to certain SEC requirements as it relates to liquidity, thus providing a layer of protection for all shareholders. To read more about affiliate Trading Volume Formula please visit: https://www.sec.gov/about/reports-publications/investorpubsrule144 . We also acknowledge the Company’s shares have experienced significant volatility in recent months. We believe this in large part due to the expiration of the lockup of pre-IPO shares that occurred on the week of January 27, 2025. The vast majority of our pre-IPO shareholders invested in the Company to succeed in its mission of delivering a new treatment option for osteosarcoma patients. The Company expects to complete a number of key milestones towards FDA approval. We are engaging with new institutional and retail investors to expand our shareholder base. Approval of OST-HER2 for osteosarcoma on or before September 30, 2026 (the Company is targeting a late 2025 approval) would grandfather into the FDA’s sunsetting Priority Review Voucher (“PRV”) program by virtue of the Rare Pediatric Disease Designation (“RPDD”) the FDA granted to the Company in 2021. This would result in non-dilutive capital, expected in the $150 million range. Regulatory Path to Approval for OST-HER2 in Osteosarcoma On January 15, 2025, the Company announced that it achieved the primary endpoint with statistical significance in its Phase 2b clinical trial of OST-HER2 in the prevention of recurrent, fully resected, lung metastatic osteosarcoma. In discussions prior to the initiation of the Phase 2b study, FDA recommended 12-month Event Free Survival as the primary endpoint for a successful objective treatment response (“Responders”). The data showed that in comparison with the best available historical control group from United States published literature (the “Published Control”): 33% of OST-HER2 patients were Responders vs. 20% in the Published Control. A greater proportion of OST-HER2 treated patients vs. the Published Control were alive at the post-Resection interim 12-month timepoint (91% vs. 80%) and 24-month timepoints (61% vs. 40%) than the Published Control, in the 3-year overall survival secondary endpoint. 100% of patients on OST-HER2 who were disease free at 12 months were alive at the 12-month, 18-month, 24-month and 30-month timepoints, as of each of their last dates of contact. OST-HER2 was well tolerated, with a strong safety profile that is sufficient to support regulatory approval. Additionally, in preparation for further regulatory discussions with FDA regarding submission of OST-HER2 for accelerated or full approval, the Company sourced the only available database of osteosarcoma patients treated with the standard of care in the US to establish a matched historical external control arm (the “Matched Control”). We did this after receiving feedback from FDA regarding a Breakthrough Therapy Designation (“BTD”) request that noted the clinical subpopulation we studied in the Phase 2b trial met the BTD criteria and that a matched historical external control would be required to determination clinical efficacy. The Matched Control will provide the clinical comparator required by FDA to support approval, based on advice from senior regulatory advisors with experience in getting pediatric orphan therapies approved. While there were insufficient numbers of data points available to finalize the submission package for FDA as of January 2025, the interim data collected on the Primary Endpoint showed: 33% of OST-HER2 treated patients were Responders vs. 11% in Matched Control In Non-Responders, the average time to recurrence was 5.9 months in OST-HER2 treated patients vs. 4.7 months in Matched Control. In further discussions with key members of our Regulatory and Scientific Advisory Board, subgroup analyses that focused on the response to therapy among patients at different stages of disease offered important insight into the potential importance of OST-HER2 for patients and clinicians in osteosarcoma. In the OST-HER2 treated group: Patients who had multiple Resections (2+) showed greater propensity (55%) for achieving 12-month EFS than patients who had previously had only one Resection (25%); Patients who previously had only one Resection (25%) still performed better than patients from the Published Control (20%) and the Matched Control (11%). The likelihood that patients who have had multiple lung metastasis resections were Responders at a 55% rate was important to clinicians because patients with 1 prior Resection will likely progress to having multiple resections, with near 100% certainty. This makes OST-HER2 a therapy likely appropriate for a large proportion of patients. Taken together, the Company believes the efficacy data Matched Control will ultimately support regulatory approval in the prevention of metastases in osteosarcoma, considering the lack of options available in the market, the poor survival outcomes for patients and the strong safety profile of OST-HER2. The Company is working with both domestic and European osteosarcoma research groups to gather additional non-concurrent control arm data for FDA review. The Company intends to request a meeting (either Type B or Type C) with FDA to review the data and discuss the path towards BLA once the additional Matched Control data is ready for submission, expected in the first quarter of 2025. The Company expects meeting with FDA early in the second quarter of 2025. Later in the second quarter we plan to file the BLA, provided positive feedback from FDA. Upon filing the BLA, the Company expects approval within 6 months. Additionally, the Company owns the rights to OST-HER2 in canines , with strong efficacy data previously published. While the Company has prioritized development of OST-HER2 for humans with osteosarcoma, it does intend to make progress in making the conditionally-approved treatment available where possible while it works to secure full regulatory approval so that it can be made broadly accessible. Additional information will be forthcoming on this effort in the months ahead. Acquisition of Clinical Assets and IP from Ayala On January 29, 2025, the Company announced that it entered into an agreement to acquire certain clinical and intellectual property assets from Ayala (the “Acquisition”). As a result of the Acquisition, the Company gained rights to two new Listeria -based clinical-stage immunotherapy candidates: ADXS-503 for lung cancer and ADXS-504 for prostate cancer. While the clinical data for these candidates is encouraging, the primary reason the Company moved forward with the Acquisition was to eliminate an expected near-term cash milestone of $3.5 million due upon the earlier of receiving FDA approval of OST-HER2 or initiating a pivotal trial for OST-HER2 in a clinical indication. Given the likelihood that the recently completed Phase 2b clinical trial of OST-HER2 would be considered pivotal by virtue of the expectation that FDA will allow the data gathered to become the primary efficacy data utilized for BLA submission, this agreement reduces our expected cash needs for 2025. Additionally, the Acquisition reduces the Company’s royalty rate from 10% to 1.5% of net sales and eliminates $16.5 million in milestones on the first $100 million in sales, dramatically improving the potential margin gained by the Company in the early years for OST-HER2 in osteosarcoma. The Company is now positioned as the clear market leader in Listeria -based immunotherapy, a long-promising class of cancer immunotherapy. We expect it to become an important treatment option in situations where no treatments exist, such as recurrent, metastatic osteosarcoma, as well as an adjunct to the standard of care where treatment fails or is insufficient. There was previously considerable enthusiasm around the use of Listeria as an immunotherapy platform in cancer, and we believed this enthusiasm will renew as OST-HER2 makes its way through the FDA approval process. Strategic options for our tunable Antibody & other Drug Conjugate platform With the solidification of OS Therapies as the market leader in Listeria-based immunotherapy, we expect that the development funding priorities post-approval of OST-HER2 in osteosarcoma will be to evaluate OST-HER2 in other HER2-related oncology areas, as well as identify paths forward for ADXS-503 (to be renamed OST-503) in lung cancer and ADXS-504 (to be renamed OST-504) in prostate cancer - two large therapeutic areas with significant unmet medical need. The Company will accelerate the development of our groundbreaking tunable drug conjugate platform based on pH-sensitive tunable linker technology, capable of linking multiple different therapeutic payload combinations with multiple different targeting antibodies - without using our existing cash resources for development. Given the continued market interest in combining therapeutic interventions, such as antibody and vascular targeted drugs to target specific cancer cells, we believe our tunable drug conjugate platform could play an outsized role in creating combination therapies that will improve outcomes while reducing side effects. We will announce strategic options in the near future. Conclusion Our journey as a newly public company resulted in significant clinical and business accomplishments, alongside known challenges for biotechnology companies with relatively small capitalizations. OS Therapies is different from others because the Company has completed its capital-intensive clinical development phase. We are fully funded through a potential PRV sale - a significant revenue generating milestone. These distinctions could separate OS Therapies from others in this challenging biotech funding environment as the market becomes aware of our positioning. We thank the patients, families, clinicians and investors who believe in the mission of the Company to improve outcomes for osteosarcoma, and other solid tumors. About OS Therapies OS Therapies is a clinical stage oncology company focused on the identification, development, and commercialization of treatments for Osteosarcoma (OS) and other solid tumors. OST-HER2, the Company's lead asset, is an immunotherapy leveraging the immune-stimulatory effects of Listeria bacteria to initiate a strong immune response targeting the HER2 protein. OST-HER2 has received rare pediatric disease, fast-track and orphan drug designations from the US FDA. The Company has completed enrollment for a 41-patient Phase 2b clinical trial of OST-HER2 in recurrent, fully resected, lung metastatic osteosarcoma, with positive results released in the first quarter of 2025. The Company anticipates submitting a Biologics Licensing Application (BLA) to the US FDA for OST-HER2 in osteosarcoma in 2025 and, if approved, would become eligible to receive a Priority Review Voucher that it could then sell. OST-HER2 has completed a Phase 1 clinical study primarily in breast cancer patients, in addition to showing preclinical efficacy data in various models of breast cancer. OST-HER2 has been conditionally approved by the U.S. Department of Agriculture for the treatment of canines with osteosarcoma. In addition, OS Therapies is advancing its next-generation Antibody Drug Conjugate (ADC) platform, known as tunable ADC (tADC), which features tunable, tailored antibody-linker-payload candidates. This platform leverages the Company's proprietary silicon linker technology, enabling the delivery of multiple payloads per molecule. For more information, please visit www.ostherapies.com . Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of the federal securities laws. These forward-looking statements and terms such as "anticipate," "expect," "intend," "may," "will," "should" or other comparable terms involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. Those statements include statements regarding the intent, belief or current expectations of OS Therapies and members of its management, as well as the assumptions on which such statements are based. OS Therapies cautions readers that forward-looking statements are based on management’s expectations and assumptions as of the date of this news release and are subject to certain risks and uncertainties that could cause actual results to differ materially, including, but not limited to the approval of OST-HER2 by the US FDA and grant of a priority review voucher and other risks and uncertainties described in “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in the Company’s registration statement on Form S-1 filed with the Securities and Exchange Commission (the “SEC”) on November 12, 2024, as amended on November 27, 2024, and other subsequent documents we file with the SEC, including but not limited to our Quarterly Reports on Form 10-Q. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by the federal securities laws, OS Therapies specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.