DiGeorge Syndrome

Data to be Presented at the Hot Topics in Child Neurology Podium Presentation Session at the American Academy of Neurology Annual Meeting PLYMOUTH MEETING, Pa.--(BUSINESS WIRE)--Apr. 8, 2025-- Harmony Biosciences Holdings, Inc. (Nasdaq: HRMY) today announced the presentation of updated data from its Open-Label Extension (OLE) study (ZYN2-CL-017) evaluating the safety and effectiveness of ZYN002 in children, adolescents, and adults with Fragile X syndrome (FXS). The data showed clinically meaningful improvements in irritability-related symptoms prevalent in individuals with FXS. There are currently no U.S. Food & Drug Administration (FDA) approved treatments for FXS. The data will be shared during a podium presentation at the American Academy of Neurology (AAN) 2025 Annual Meeting’s “Hot Topics in Child Neurology” session on Tuesday, April 8, 2025, at 3:30 PM PT in San Diego, CA. “The acceptance of our Fragile X syndrome OLE data as a podium presentation at AAN underlines the significant unmet need in FXS, and the potential for ZYN002 to become the first-and-only approved treatment for this condition,” said Kumar Budur, MD, MS, Chief Medical and Scientific Officer at Harmony Biosciences. “These data are encouraging as we prepare for the topline data readout from our ongoing Phase 3 registrational trial, the RECONNECT study, in Q3 2025. Approximately 80,000 individuals are living with this rare neurological disease in the U.S. alone and Harmony is deeply committed to addressing the profound unmet medical needs of this community both in the U.S. and globally.” Participants entered the OLE trial from the Phase 2/3 CONNECT-FX trial, and the Phase 1/2 FAB-C signal detection open-label trial. Participants in the OLE trial demonstrated clinically meaningful improvements in behavioral symptoms as measured by the Aberrant Behavior Checklist – Community (ABC-CFXS Irritability). This included participants who received active treatment in the double-blind, placebo-controlled CONNECT-FX trial, and those who transitioned from placebo to treatment in the OLE. More than 60% of participants in both groups achieved clinically meaningful improvement of at least 9 points on the ABC-CFXS Irritability scores at two consecutive visits. Additionally, 40.6% of participants who received active treatment in the CONNECT-FX trial were rated by their caregivers as demonstrating a clinically meaningful improvement in behavior based on the Caregiver Global Impression of Change (CaGI-C) scores, compared to 29.8% who received placebo in the CONNECT-FX trial. After three years, 73.3% of patients who continued on ZYN002, as well as 72% who transitioned from placebo to ZYN002, experienced clinically meaningful improvements. Serious treatment-emergent adverse events were reported in 4.6% of patients in the OLE, with discontinuation occurring in 3.3% of patients. Treatment-related adverse events were observed in 12.9% of patients, none of which were serious, and the most common of these adverse events was pain at the treatment application site in 6.7% of patients. The data presented at AAN covers the period from September 2018 to January 31, 2024, and included 240 patients administered ZYN002 at doses of 250, 500, or 750 mg per day based on their weight. The mean age of the patients was 9.7 years and ranged from 3 to 17 years. ZYN002 is currently being evaluated as an investigational treatment for FXS in the RECONNECT study, a Phase 3 randomized, double-blind, placebo-controlled registrational trial evaluating the safety and efficacy of ZYN002 in patients with FXS ages 3 to under 30 years. ZYN002 is not approved by the FDA for the treatment of FXS. About ZYN002 ZYN002 is the first-and-only pharmaceutically manufactured synthetic cannabidiol devoid of THC and formulated as a patent-protected permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. The product is manufactured through a synthetic process in a cGMP facility and is not extracted from the cannabis plant. ZYN002 does not contain THC, the compound that causes the euphoric effect of cannabis, and has the potential to be a nonscheduled product if approved. Cannabidiol, the active ingredient in ZYN002, has been granted Orphan Drug Designation by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of FXS and for the treatment of 22q11.2 deletion syndrome (22q). Additionally, ZYN002 has received FDA Fast Track designation for the treatment of behavioral symptoms in patients with FXS. About Fragile X Syndrome Fragile X syndrome (FXS) is a rare genetic disorder that is the leading known inherited cause of both intellectual disability and autism spectrum disorder. The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. While the exact prevalence is unknown, upwards of 80,000 patients in the U.S. and 121,000 patients in the European Union and the UK are believed to have FXS, based on FXS prevalence estimates of approximately 1 in 4,000 to 7,000 in males and approximately 1 in 8,000 to 11,000 in females. There is a significant unmet medical need in patients living with FXS as there are currently no FDA-approved treatments for this disorder. FXS is caused by a mutation in FMR1, a gene which modulates a number of systems, including the endocannabinoid system, and most critically, codes for a protein called FMRP. The FMR1 mutation manifests as multiple repeats of a DNA segment, known as the CGG triplet repeat, resulting in deficiency or lack of FMRP. FMRP helps regulate the production of other proteins and plays a role in the development of synapses, which are critical for relaying nerve impulses, and in regulating synaptic plasticity. In people with full mutation of the FMR1 gene, the CGG segment is repeated more than 200 times, and in most cases causes the gene to not function. Methylation of the FMR1 gene also plays a role in determining functionality of the gene. In approximately 60% of patients with FXS, who have complete methylation of the FMR1 gene, no FMRP is produced, resulting in dysregulation of the systems modulated by FMRP. About Harmony Biosciences Harmony Biosciences is a pharmaceutical company dedicated to developing and commercializing innovative therapies for patients with rare neurological diseases who have unmet medical needs. Driven by novel science, visionary thinking, and a commitment to those who feel overlooked, Harmony Biosciences is nurturing a future full of therapeutic possibilities that may enable patients with rare neurological diseases to truly thrive. Established by Paragon Biosciences, LLC, in 2017 and headquartered in Plymouth Meeting, Pa., we believe that when empathy and innovation meet, a better future can begin; a vision evident in the therapeutic innovations we advance, the culture we cultivate, and the community programs we foster. For more information, please visit www.harmonybiosciences.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding our future results of operations and financial position, business strategy, products, prospective products, product approvals, the plans and objectives of management for future operations and future results of anticipated products. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the timing of, and our ability to obtain, regulatory approvals for our product candidates; our estimates regarding expenses, future revenue, capital requirements and additional financing needs; our ability to identify, acquire and integrate additional products or product candidates with significant commercial potential that are consistent with our commercial objectives; our commercialization, marketing and manufacturing capabilities and strategy; significant competition in our industry; our intellectual property position; loss or retirement of key members of management; failure to successfully execute our growth strategy, including any delays in our planned future growth; our failure to maintain effective internal controls; the impact of government laws and regulations; volatility and fluctuations in the price of our common stock; the significant costs and required management time as a result of operating as a public company; the fact that the price of Harmony's common stock may be volatile and fluctuate substantially; statements related to our intended share repurchases and repurchase timeframe and the significant costs and required management time as a result of operating as a public company. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K filed with the Securities and Exchange Commission (the "SEC") on February 25, 2025, and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. View source version on businesswire.com: https://www.businesswire.com/news/home/20250408261652/en/ Harmony Biosciences Investor Contact: Brennan Doyle 484-539-9700 bdoyle@harmonybiosciences.com Harmony Biosciences Media Contact: Cate McCanless 202-641-6086 cmccanless@harmonybiosciences.com Source: Harmony Biosciences Holdings, Inc.

Tolerance Bio has launched with an oversubscribed $17.2 million seed round and a goal to develop therapies for immune-mediated diseases, from cancer to transplant rejection, using the thymus. The Philadelphia-based company plans to develop an allogeneic thymus-induced pluripotent stem cell (iPSC)-based cell therapy platform as well as thymus therapies in an effort to target immune diseases at their core. Columbus Venture Partners led the funding round. Other investors include Criteria Bio Ventures, Sessa Capital, BioAdvance and Ben Franklin Technology Partners. Tolerance is focusing on the thymus, an organ that plays an important role in training and maturing the body’s T cells to defend against immune issues like infections and cancers while also preventing autoimmunity. The T cells in the human body are developed in the first two years of life, but the thymus declines with age, leading to a higher risk for immune diseases. Tolerance hopes to delay and prevent the decline of the thymus, as well as restore the organ if it stops functioning. Tolerance CEO Francisco Leon, who co-founded Provention Bio, which was acquired by Sanofi for $2.9 billion in 2023, said that the startup plans to focus on a rare disease before turning to other indications. Tolerance’s first approach will be focused on restoring thymic function with an adult stem cell-derived thymic epithelial cell implant. “We can generate thymic cells in the lab from stem cells. And we can implant them into an animal, and they develop into a mini-thymus in the body of the animal. Then they train new T cells, and this is already done and published,” Leon told Endpoints News . As a preclinical proof-of-principle of the technology’s potential, Tolerance implanted these stem cells into mice that have no thymus, a well-known animal model of immune deficiency that has the same mutation as babies born without the thymus, a condition called DiGeorge syndrome. “By transplanting our thymic epithelial progenitors, we can generate a lot of T cells simply by implanting the thymic epithelial progenitors,” Leon added. “This is our first preclinical proof of concept.” At the same time, Tolerance is going to use these thymic cells combined with antigens for autoimmune diseases and cancer in order to explore whether they can induce tolerance in autoimmune diseases as well as tumor immunity in cancer. “This is not published yet, but we have a paper under review that shows we can educate the T cells to attack melanoma,” Leon said. “This is going to come out in a few months, probably after the review process.” A third aspect of a six-year plan is drug repositioning, where Tolerance will give people a drug to delay or prevent the involution of the thymus for those who still have a thymus. The target is still undisclosed, but it’s something the company will do in the coming months.

October 2024 – Genewity is proud to announce that earlier this year, i-Thymus has been granted Orphan Drug Designation by both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for the treatment of congenital athymia. This recognition from both regulatory bodies marks an important milestone for the development of i-Thymus and highlights its potential to address a critical unmet medical need. ‍ Acceleration forGenewity The Orphan Drug Designation brings several key benefits that will accelerate the development of i-Thymus. Most significantly, it grants market exclusivity for up to ten years in Europe and seven years in the U.S. following approval, ensuring a strong competitive position in both markets. Genewity will also gain financial incentives, including reduced regulatory fees in the EU and tax credits for clinical trials in the U.S., which will help lower development costs and extend the company's resources. ‍ In addition, both the EMA and FDA offer regulatory support to companies developing orphan drugs. This includes personalised guidance on clinical trial design and the overall regulatory pathway, reducing risks and increasing the likelihood of approval. This support will be critical as Genewity advances i-Thymus toward manufacturing under Good Manufacturing Practices (GMP) and investigations at clinical stage. ‍ Acceleration for patients with congenital athymia Congenital athymia, as seen in patients with complete DiGeorge syndrome, currently has limited treatments available. One, for example, is used in the U.S. but depends on the availability of donor tissue, which limits its accessibility and effectiveness for many patients. Genewity’s i-Thymus is designed to tackle the underlying cause of the disease at a genetic level with an autologous and potentially curative approach. By modifying a patient’s own cells to create functional autologous thymus tissue, i-Thymus could bring a transformative therapy to patients who urgently need it, providing them with a chance to develop a functioning immune system and significantly improving their quality of life. ‍ What is next for Genewity “Securing orphan designation in both Europe and the U.S. is a huge achievement for our small, ambitious team,” said Dr. Arno Bisschop, CEO of Genewity. “This validation strengthens our confidence in the potential of i-Thymus to make a real difference in the lives of patients without a functioning thymus. We are eager to move forward and take the next steps toward clinical development.” With the Orphan Drug Designations in place, Genewity will be able to advance i-Thymus more quickly towards the clinic. Having the support of the EMA and FDA, i-Thymus is optimally positioned to create significant value for patients. About Genewity Genewity Holding B.V. is a biotechnology company based at the Leiden Bioscience Park, Netherlands, specialising in the development of advanced treatments using extracorporeal gene therapy with lentiviral vectors. This technology enables the modificationof stem cell characteristics, opening new avenues for innovative gene-modified cell therapies. The company focuses on generating thymus cells from pluripotent stem cells to develop treatments for congenital athymia and autoimmune diseases. ‍