Paraparesis, Spastic

Pictured: 3D illustration of a short single-stranded oligonucleotide iStock, Dr_Microbe In a Phase I/II study, Ultragenyx’s antisense oligonucleotide GTX-102 led to significant cognitive, behavioral, sleep and gross motor improvements in patients with the rare genetic disorder Angelman syndrome. Ultragenyx Pharmaceutical on Monday provided a Phase I/II update for its investigational antisense oligonucleotide GTX-102, demonstrating substantial symptomatic improvement in patients with the rare genetic disorder Angelman syndrome. The California biotech did not provide specific data in its announcement but said that patients in its dose-escalation cohorts saw “rapid and clinically significant improvement” in cognition after 170 days, compared with natural history data. These patients also demonstrated strong behavioral, sleep, hyperactivity, gross motor and receptive communication improvements after GTX-102 treatment, the company announced. Ultragenyx CMO Eric Crombez in a statement that these interim data show “that treatment with GTX-102 resulted in rapid, multi-domain improvements that continued throughout maintenance dosing,” which in turn could have a “meaningful impact on patients and their families.” Some children have been able to start eating on their own and communicate with their families, Crombez noted. “Our next step is an end of Phase II meeting with the FDA and interactions with other health authorities to enable timely initiation of a Phase III pivotal study,” Crombez added. Despite these positive findings, Ultragenyx’s shares fell 7% on Monday, according to Seeking Alpha . Much of the investors’ apprehension could be due to GTX-102’s safety profile. In the Phase I/II study, Ultragenyx documented three cases of lower extremity weakness, which were deemed serious adverse events and related to the study treatment. All instances were quickly resolved and the patients remain on GTX-102 treatment with no new safety signals. The FDA has also been notified of these safety events but has so far raised no issues or asked for other actions, according to Ultragenyx. Angelman syndrome is a rare and neurogenetic disorder caused by a loss-of-function mutation in the maternal allele of the UBE3A gene, which under normal circumstances produces an enzyme that tags other proteins for destruction. Symptoms include cognitive, motor and balance impairment, as well as debilitating seizures. Patients also typically develop anxiety and difficulties sleeping. GTX-102, an intrathecal investigational antisense oligonucleotide, works by targeting and blocking the expression of the UBE3A-AS gene, which otherwise produces a protein that silences the paternal copy of UBE3A. Nonclinical studies have shown that this mechanism of action reactivates UBE3A expression in neurons, leading to neurological improvements. Ultragenyx is facing competition in the Angelman syndrome space from Ionis, which is developing its own antisense treatment ION582 . Like GTX-102, Ionis’ candidate un-silences the paternal copy of the UBE3A gene to reactivate the production of the protein in neurons. ION582 won the FDA’s Orphan Drug and Rare Pediatric Disease designations in June 2022. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

COLLEGE STATION, TX / ACCESSWIRE / May 26, 2021 / Enzolytics, Inc. (OTC PINK:ENZC) (the "Company") today announced it has identified conserved, expectedly immutable sites on the HTLV-1 virus against which it will produce targeted anti-HTLV-1 monoclonal antibodies (mAbs). There are no effective vaccines against HTLV-1 and no antiviral drugs available for treating infections caused by the virus. Utilizing the Company's proprietary Artificial Intelligence (AI) methodology, conserved target sites have now been identified against which fully human anti-HTLV-1 monoclonal antibodies will be produced in its lab on the campus of Texas A&M University in the University's Institute for Preclinical Studies. The Company's own Artificial Intelligence team continues to identify the critical sites on viruses against which monoclonal antibodies will be produced to treat infectious viral diseases. Experts recognize the significance of producing multiple monoclonal antibodies targeting multiple conserved sites as a necessary approach to effective therapy. This allows the administration of a "cocktail" of antibodies, all targeting conserved and expectedly immutable sites. Adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) are several diseases associated with HTLV-1. More than 20 million people worldwide are infected with the virus. Up to 10% will develop the debilitating and sometimes deadly disease. HTLV-1 causes adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy (HAM), spastic paraparesis, and other rare illnesses. Signs and symptoms of HTLV-1 infection include motor and sensory changes in the extremities, inflammation in the spinal cord, a spastic gait in combination with weakness of the lower limbs, cognitive impairment, bladder dysfunction, and bladder cancer. HTLV-1 is similar to the human immunodeficiency virus (HIV), is transmitted through sexual contact, from mother to child via breastfeeding and through exposure to contaminated blood. HTLV-1 requires cell-to-cell contact for efficient transmission. The virus utilizes Envelope (Env) glycoprotein-mediated cell binding and entry. Using Enzolytics' proprietary AI methodology, multiple conserved sites have been identified in the outer envelope of the HTLV-1 virus. Enzolytics continues to harness the power of artificial intelligence, in conjunction with the Company's proprietary fully human monoclonal antibody methodology, to create universal, durable, broadly neutralizing monoclonal antibodies against multiple viruses, now to include monoclonal antibodies against HTLV-1. Charles Cotropia, CEO of Enzolytics, said: "We now have a comprehensive platform for producing multiple targeted monoclonal antibodies against numerous infectious diseases. This platform includes our ability to first identify multiple conserved and expectedly immutable sites on viruses with the ability to then produce fully human monoclonal antibodies targeting those sites. This approach opens the door to new and durable therapies that can be used to treat innumerable human infectious diseases." About Enzolytics, Inc. Enzolytics, Inc. is a drug development company committed to the commercialization of its multiple proprietary therapeutics to treat debilitating infectious diseases. The Company's patented ITV-1 therapeutic is a suspension of Inactivated Pepsin Fraction (IPF), which studies have shown effectively treats HIV/AIDS. IPF is the active component of ITV-1 and is a purified extract of porcine pepsin. ITV-1 has also been shown to modulate the immune system. Additionally, the Company has a proprietary technology for producing fully human monoclonal antibodies (mAbs) against infectious diseases including HIV, rabies, influenza A, influenza B, tetanus, and diphtheria. Its proprietary methodology for producing fully human monoclonal antibodies is currently employed to produce monoclonal antibody therapeutics to treat other infectious diseases including the Coronavirus (SARS-CoV-2). Safe Harbor Statement: This news release contains forward-looking statements that involve risks and uncertainties associated with financial projections, budgets, milestone timelines, clinical development, regulatory approvals, and other risks described by Enzolytics, Inc. from time to time in its periodic reports filed with the SEC. ITV-1 is not approved by the U.S. Food and Drug Administration or by any comparable regulatory agencies elsewhere in the world. While Enzolytics, Inc. believes that the forward-looking statements and underlying assumptions contained therein are reasonable, any of the assumptions could be inaccurate, including, but not limited to, the ability of the Company to establish the efficacy of ITV-1 or its other therapeutics in the treatment of any disease or health condition, the development of studies and strategies leading to commercialization of its therapeutics in the United States, the obtaining of funding required to carry out the development plan, the completion of studies and tests on time or at all, and the successful outcome of such studies or tests. Therefore, there can be no assurance that the forward-looking statements included in this release will prove to be accurate. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of the statements made, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. These forward-looking statements are made as of the date of this press release. The Company expressly disclaims any intention or obligation to update the forward-looking statements or update the reasons why actual results could differ from those projected in the forward-looking statements. IR Contact: TEN Associates, LLC Tom Nelson, CEO (480) 326-8577 Investor Relations Company Contact: Enzolytics, Inc. 2000 North Central Expressway Plano, TX 75074 Research Center Enzolytics, Inc. Texas A&M University Institute for Preclinical Studies College Station, TX 77843-44 SOURCE: Enzolytics, Inc. View source version on accesswire.com:

August 9, 2016 By Mark Terry , BioSpace.com Breaking News Staff Aldeyra Therapeutics , headquartered in Lexington, Massachusetts, announced positive data from a clinical trial of its topical NS2 to treat skin conditions caused by Sjogren-Larsson Syndrome (SLS). SLS is a rare disease caused by a problem with aldehyde metabolism. It results in mental retardation, spastic paraparesis, macular dystrophy, leukoencephalopathy, and ichthyosis. Ichthyosis is a dermatologic disease that results in dry, thickened, scaly skin. NS2 is being tested to treat ichthyosis in SLS patients. The study was on 12 patients with SLS and moderate to severe ichthyosis. NS2 showed clinically meaningful results in cutting the severity of ichthyosis compared to patients treated with placebo. “The results of this randomized and controlled clinical trial represent a significant advance in the effort to develop a treatment for SLS,” said William Rizzo , the principal investigator of the trial, in a statement. “The data from this trial suggest that NS2, when applied topically to the skin, has the potential to help patients suffering from SLS by lowering toxic aldehyde levels and preventing the dermal dysfunction that causes ichthyosis. I am excited about these results, and I am particularly excited for SLS patients and their caregivers.” Aldeyra employs 12 people and has been noted for having Massachusetts’ smallest biotech initial public offering (IPO) in recent years. In May 2014, when the company had only two employees, it raised $12 million. Aldeyra outsources all its laboratory and development work and labors to keep costs down. It has spent $19 million over the past two calendar years. It has conducted two previous clinical trials, both mid-stage studies, to test NS2 formulated as an eye drop in 100 patients with allergic conjunctivitis and 45 patients with anterior uveitis. “This is our third trial (reported this year), and it’s worked in all three,” said Todd Brady , the company’s chief executive officer, to the Boston Business Journal. Speaking about today’s announcement, he said, “We’re particularly thrilled because this is an indication with no approved therapies.” NS2 binds, or “traps” aldehydes, which are toxic and involved in inflammatory pathways in a number of diseases. NS2 appears to decrease the aldehyde load, which decreases inflammation and has potential treatment in diseases where aldehyde metabolism is not working properly. Aldeyra is currently trading for $6.68 per share. The company is announcing its second-quarter financial results tomorrow. Cowen and Company reiterated a “buy” rating for the company on Tuesday, May 10. Stifel Nicolaus issued a “buy” rating and a $16 price target on July 1. Aldeyra has an average “buy” rating and consensus price target of $13.13. At this point, Brady told the Boston Business Journal that he plans to discuss development plans with the U.S. Food and Drug Administration (FDA) . It’s not clear if the 12-patient study, given the rarity of the disease, will be enough to apply for regulatory approval. He also indicated he plans to talk to European regulators. SLS is more common in Sweden and Norway. And Aldeyra has plans to start a trial for an oral formulation of the drug next year, which it hopes might be effective in treating neurological components of the disease, not just dermatological symptoms.