Fosfomycin Sodium

Captisol-enabled™ Topiramate Injection shown to be a substitute for an oral dose on a one-to-one basis LONDON--(BUSINESS WIRE)-- Ligand Pharmaceuticals Inc. Incorporated (Nasdaq: LGND) today announced that its partners at the University of Minnesota (UMN) and CURx Pharmaceuticals, Inc. presented new data on Captisol-enabled™ Topiramate Injection (IV topiramate), a potential replacement therapy for the treatment of certain emergent neurological conditions, including epilepsy, when oral administration is not feasible. The poster was featured at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures Conference in London, England. The authors presented modeling and simulations of IV topiramate dosing based on previous studies conducted by UMN faculty in healthy research participants and patients. In addition, preliminary pharmacokinetic data was presented from 25 healthy participants in a CURx ongoing randomized, single-center, open-label, cross-over clinical study for an investigational intravenous (IV) formulation of topiramate, an antiseizure and anti-migraine medication. “The IV formulation of topiramate can be used as replacement therapy; but additionally, small studies in neonates and patients with prolonged seizures indicate it may have a role in treating these conditions if future studies demonstrate benefit,” said James Cloyd, Pharm.D., Director of the Center for Orphan Drug Research at the University of Minnesota College of Pharmacy, co-author of the poster, and a principal investigator on several IV topiramate studies. “Based on our research, we believe clinicians can now properly dose IV topiramate in a variety of clinical situations, including the use of loading doses to rapidly attain targeted plasma drug concentrations in patients when there is a delay in initiating replacement therapy, in patients who are getting topiramate for the first time, and in those taking a co-medication that increases the elimination of topiramate.” “This poster incorporates preliminary pharmacokinetic data from our recent study in healthy research subjects in which an intravenous dose of topiramate was compared to a dose of oral topiramate to assess safety and the dose of the IV topiramate needed to replicate the plasma concentrations following oral administration,” commented Bernard King, M.D., Chief Medical Officer of CURx and co-author of the poster. “Our findings confirm that IV topiramate can be substituted for an oral dose on a one-to-one basis, thus simplifying replacement therapy.” IV topiramate is an investigational formulation of topiramate designed for the treatment of partial onset or primary generalized tonic-clonic seizures in hospitalized epilepsy patients and treatment of epilepsy patients in an emergency care setting who are unable to take oral topiramate. Ligand licensed the rights to the IV formulation of topiramate from UMN and entered into a global license agreement with CURx Pharmaceuticals to further develop and commercialize the product. IV topiramate has been granted Orphan Drug Designation by the U.S. Food and Drug Administration and Ligand is entitled to net milestone payments and a mid-single-digit royalty on global sales. “Our longtime partners are making much-needed progress for people managing epilepsy, and it is exciting to see that,” said James Pipkin, Ph.D., Vice President of New Product Development at Ligand. “The availability of an injectable topiramate formulation will make it possible to ensure continuity of therapy. Captisol is what enables this and other new formulations, which give patients more options and flexibility when it comes to maintaining their medication regimens.” Abstract 305 “A Comparison of IV and Oral Topiramate Pharmacokinetics in Healthy Participants, Patients with Migraines, and Patients with Epilepsy with or without Concomitant Enzyme-Inducing Drugs” was presented by the poster co-authors at the University of Minnesota College of Pharmacy. About Captisol® Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella, University Distinguished Professor at the University of Kansas' Higuchi Biosciences Center, for specific use in drug development and formulation. This unique technology has enabled several FDA-approved products, including Amgen's Kyprolis®, Baxter's NEXTERONE, Acrotech Biopharma's EVOMELA®, Sage Therapeutics' ZULRESSO®, Gilead’s VEKLURY®, and Merck's NOXAFIL®. There are more than 40 active Captisol-enabled™ partnered programs in various stages of development. More information is available at . About Ligand Pharmaceuticals Ligand is a biopharmaceutical company enabling scientific advancement through supporting the clinical development of high-value medicines. Ligand does this by providing financing, licensing our technologies or both. Our business model seeks to generate value for stockholders by creating a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable and diversified manner. Our business model is based on funding programs in mid- to late-stage drug development in return for economic rights and licensing our technology to help partners discover and develop medicines. We partner with other pharmaceutical companies to attempt to leverage what they do best (late-stage development, regulatory management and commercialization) in order to generate our revenue. Our Captisol® platform technology is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. We have established multiple alliances, licenses and other business relationships with the world’s leading pharmaceutical companies including Amgen, Merck, Pfizer, Jazz, Takeda, Gilead Sciences and Baxter International. For more information, please visit . Follow Ligand on X @Ligand_LGND. We use our investor relations website and X as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Investors should monitor our website and our X account, in addition to following our press releases, SEC filings, public conference calls and webcasts. About the University of Minnesota The University of Minnesota System, with campuses in Crookston, Duluth, Morris, Rochester, and the Twin Cities, is driven by a singular vision of excellence. We are proud of our land-grant mission of world-class education, groundbreaking research, and community-engaged outreach, and we are unified in our drive to serve Minnesota. Visit system.umn.edu. About CURx Pharmaceuticals CURx Pharmaceuticals is a specialty pharmaceutical company that licenses, develops and commercializes products that address unmet medical needs. The company is focused on searching for and licensing candidates for development based on sound scientific rationale; strong preclinical and clinical study results; defined regulatory pathway to approval; robust intellectual property protection; and defined market need, and to date has licensed three mid- to late-stage molecules. CURx Pharmaceuticals’ lead clinical asset is Fosfomycin Tobramycin for Inhalation (FTI), which is being developed as a treatment for patients with Cystic Fibrosis. For more information visit . Forward-Looking Statements This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as “plans,” “believes,” “expects,” “anticipates,” and “will,” and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include: the potential that topiramate injection can benefit patients who would otherwise be treated via oral administration; and the potential royalties to be paid on sales of topiramate injection by CURx Pharmaceuticals. Actual events or results may differ from Ligand’s or its partner’s expectations due to risks and uncertainties inherent in Ligand’s and its partner’s business, including, without limitation: CURx Pharmaceuticals may not be able to successfully commercialize topiramate injection which will depend on a number of factors including coverage and reimbursement levels from governmental authorities and health insurers as well as market acceptance by healthcare providers; the market size for topiramate injection may be smaller than estimated; Ligand is dependent on CURx Pharmaceuticals for the commercialization of topiramate injection; and other risks described in Ligand’s prior press releases and filings with the Securities and Exchange Commission available at . Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

The Centers for Disease Control and Prevention recently issued an advisory about a bacteria called shigella. The agency is warning the public about shigella because of a nationwide increase in infections resulting from drug-resistant strains. Shigella causes an infection called shigellosis that is uncomfortable and unpleasant but rarely life-threatening. Here are seven things to know about the bacteria and the impact it is having on the country’s public health: Antibiotic-resistant cases of shigellosis are on the rise. In 2015, none of the cases of shigellosis reported to the CDC involved a drug-resistant strain. However, 5% of all shigella infections reported to the agency last year were caused by a drug-resistant strain. These strains are proliferating and likely to continue infecting Americans, the CDC said in its advisory. The agency defines drug-resistant shigella as strains that are resistant to all of the commonly recommended antibiotics for stomach bugs: azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole and ampicillin. This rise in drug-resistant shigella strains is concerning because these strains can spread antimicrobial resistance genes to other stomach bacteria, the CDC pointed out. Shigella’s main symptom is inflammatory diarrhea. Shigellosis typically causes inflammatory diarrhea, which is often bloody or mucus-laced. The infection can also cause fever, abdominal cramping and tenesmus (the painful feeling of needing to pass stool when the bowels are already empty). People usually begin to experience these symptoms one to three days after being exposed to shigella, and the symptoms typically last about a week. Some people infected with shigella will experience no symptoms at all, but they can still pass the bacteria to others. In some cases, it can take several months before an infected person’s bowel habits become normal again, according to the CDC. The agency also noted that severe shigella infections can spread into a person’s blood, which can be life-threatening. The bacteria is easily transmissible. Shigella is transmitted by the fecal-oral route. People can contract the bacteria through person-to-person contact with an infected person or through contact with contaminated food, water or surfaces. The bacteria is transmitted easily because of its low infectious dose — as few as 10-100 organisms — the CDC said. Shigella isn’t anything new, but this new wave of drug-resistant infections is. Historically, children ages one to four who are not fully toilet-trained were the main population becoming infected with the bacteria. However, the nationwide rise in drug-resistant shigellosis is occurring primarily among men who have sex with men, the homeless population, those living with HIV and international travelers, according to the CDC. Providers need to report all cases of shigellosis. The CDC has not released raw numbers about the country’s rising cases of drug-resistant shigellosis. To get better data about the spread of the bacteria, the agency is calling on healthcare providers and clinical laboratories to report all cases to their local or state health departments. The agency is also encouraging healthcare professionals to consult their local or state health department for guidance on when they can advise patients with shigellosis to return back to school, work or childcare. Providers also need to keep shigella on their radar when listening to patients’ symptoms. If a patient is experiencing acute diarrhea, their provider should consider a diagnosis of shigellosis, the CDC advised. This is especially true for patients who are LGBTQ, homeless, living with HIV or have a recent history of international travel. There is not much data on how to treat drug-resistant shigellosis. The CDC currently has no recommendations on how to treat drug-resistant shigellosis. However, a recent publication from the United Kingdom outlined two possible strategies for treating the infection. The first was using oral treatments pivmecillinam and fosfomycin, which are two antibiotics typically used to treat bladder and urinary tract infections. The other strategy involves the use of intravenous treatments carbapenems and colistin, two antibiotics that physicians usually prescribe as a last resort. This use would be intended for hospitalized patients with severe infections or complications.