Atovaquone

The U.S. medical scientific community is calling for clinical studies to expand shared understanding of babesiosis, an emerging tick-borne illness. The upcoming 60 Degrees Pharma clinical trial of tafenoquine in treating babesiosis will be the first and only such study to date. Enrollment is planned to begin in summer 2024. The Journal of Infectious Diseases has published a letter outlining the planned trial protocol. WASHINGTON, May 08, 2024 (GLOBE NEWSWIRE) -- 60 Degrees Pharmaceuticals, Inc. (NASDAQ: SXTP; SXTPW) (the “Company”), a pharmaceutical company focused on developing new medicines for infectious diseases, announced today that a letter, titled Trial Planned to Evaluate Safety and Efficacy of Tafenoquine + Atovaquone/Azithromycin in Hospitalized Babesiosis Patients, authored by the Company’s Chief Executive Officer, Geoff Dow, PhD, has been published in the Journal of Infectious Diseases. Dr. Dow’s letter responds to comments made on a recent article published in the Journal, “Tafenoquine-atovaquone combination achieves radical cure and confers sterile immunity in experimental models of human babesiosis.” Those comments, by M Liu M, EM Galon EM, S Ji, and X Xuan, called for more published medical literature on safely and effectively treating babesiosis. Dr. Dow’s response to those comments outlines plans by 60 Degrees Pharmaceuticals to launch a clinical trial to study the use of tafenoquine in treating human babesiosis. The Company plans to begin enrolling babesiosis patients this summer. The study will be the first and only of its kind in the United States to date. “A significant unmet medical need exists in North America, Europe, and Northeast Asia for new or improved methods of treatment and prevention of all forms of babesiosis, and for clinical trials dedicated to that end,” said Dr. Dow. “In close consultation with key opinion leaders in the field, we recently submitted a clinical protocol to the Food and Drug Administration. We are confident that the results of this study will add meaningfully to the global medical community’s understanding of this very serious, emerging, tick-borne infectious disease.” The 60 Degrees Pharmaceuticals babesiosis study protocol evaluates a triple combination of 800 milligrams of tafenoquine plus the recommended standard of care – which is atovaquone-azithromycin for at least 10 days – versus matching placebo and atovaquone-azithromycin in hospitalized patients with babesiosis. Tafenoquine is approved for malaria prophylaxis in the United States under the product name ARAKODA®. The safety of the approved regimen of tafenoquine for malaria prophylaxis has been assessed in five separate randomized, double-blind, active comparator or placebo-controlled trials for durations of up to six months. Tafenoquine has not been proven to be effective for treatment or prevention of babesiosis and is not approved by the FDA for such an indication. Babesiosis, a potentially life-threatening disease in immunosuppressed patients, is a tick-borne illness steadily emerging in the United States. About Babesiosis and the Tafenoquine Study This study is a randomized double-blind placebo-controlled trial anticipated to enroll at least 24 patients in the U.S. in 2024. The two main study endpoints will be time to sustained clinical resolution of symptoms of babesiosis and molecular cure as determined by an FDA-approved nucleic acid test. The study will be conducted at three hospitals in the northeastern United States. The efficacy and safety of 8-aminoquinolines, a class of drugs that includes tafenoquine and primaquine, for prevention and treatment of malaria is well established. The appearance of several case studies of tafenoquine use for babesiosis in the literature suggests that the drug is being used for this purpose in the practice of medicine in the U.S. There may be approximately 47,000 cases per year in the U.S. based on the observation of 476,000 Lyme infections and an estimated babesiosis coinfection rate of 10 percent. About ARAKODA® (tafenoquine) Tafenoquine was discovered by Walter Reed Army Institute of Research and the current study was funded by the United States Army Medical & Materiel Development Activity. Tafenoquine was approved for malaria prophylaxis in 2018 in the United States as ARAKODA®and in Australia as KODATEF®. Both were commercially launched in 2019 and are currently distributed through pharmaceutical wholesaler networks in each respective country. They are available at retail pharmacies as a prescription-only malaria prevention drug. According to the Centers for Disease Control and Prevention, the long terminal half-life of tafenoquine, which is approximately 16 days, may offer potential advantages in less-frequent dosing for prophylaxis for malaria. ARAKODA® is not suitable for everyone, and patients and prescribers should review the Important Safety Information below. Individuals at risk of contracting malaria are prescribed ARAKODA® 2 x 100 mg tablets once per day for three days (the loading phase) prior to travel to an area of the world where malaria is endemic, 2 x 100 mg tablets weekly for up to six months during travel, then 2 x 100 mg in the week following travel. ARAKODA® (tafenoquine) Important Safety Information ARAKODA® is an antimalarial indicated for the prophylaxis of malaria in patients aged 18 years of age and older. Contraindications ARAKODA® should not be administered to: Glucose-6-phosphate dehydrogenase (“G6PD”) deficiency or unknown G6PD status; Breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if G6PD status is unknown; Patients with a history of psychotic disorders or current psychotic symptoms; or Known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of ARAKODA®. Warnings and Precautions Hemolytic Anemia: G6PD testing must be performed before prescribing ARAKODA® due to the risk of hemolytic anemia. Monitor patients for signs or symptoms of hemolysis. G6PD Deficiency in Pregnancy or Lactation: ARAKODA® may cause fetal harm when administered to a pregnant woman with a G6PD-deficient fetus. ARAKODA® is not recommended during pregnancy. A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to ARAKODA® through breast milk. Check infant’s G6PD status before breastfeeding begins. Methemoglobinemia: Asymptomatic elevations in blood methemoglobin have been observed. Initiate appropriate therapy if signs or symptoms of methemoglobinemia occur. Psychiatric Effects: Serious psychotic adverse reactions have been observed in patients with a history of psychosis or schizophrenia, at doses different from the approved dose. If psychotic symptoms (hallucinations, delusions or grossly disorganized thinking or behavior) occur, consider discontinuation of ARAKODA® therapy and evaluation by a mental health professional as soon as possible. Hypersensitivity Reactions: Serious hypersensitivity reactions have been observed with administration of ARAKODA®. If hypersensitivity reactions occur, institute appropriate therapy. Delayed Adverse Reactions: Due to the long half-life of ARAKODA® (approximately 16 days), psychiatric effects, hemolytic anemia, methemoglobinemia and hypersensitivity reactions may be delayed in onset and/or duration. Adverse Reactions: The most common adverse reactions (incidence greater than or equal to 1 percent) were: headache, dizziness, back pain, diarrhea, nausea, vomiting, increased alanine aminotransferase, motion sickness, insomnia, depression, abnormal dreams and anxiety. Drug Interactions Avoid co-administration with drugs that are substrates of organic cation transporter-2 (OCT2) or multidrug and toxin extrusion transporters. Use in Specific Populations Lactation: Advise women not to breastfeed a G6PD-deficient infant or infant with unknown G6PD status during treatment and for 3 months after the last dose of ARAKODA®. To report SUSPECTED ADVERSE REACTIONS, contact 60 Degrees Pharmaceuticals, Inc. at 1- 888-834-0225 or the FDA at 1-800-FDA-1088 or The full prescribing information of ARAKODA® is located here. About 60 Degrees Pharmaceuticals, Inc. 60 Degrees Pharmaceuticals, Inc., founded in 2010, specializes in developing and marketing new medicines for the treatment and prevention of infectious diseases that affect the lives of millions of people. 60 Degrees Pharmaceuticals, Inc. achieved FDA approval of its lead product, ARAKODA® (tafenoquine), for malaria prevention, in 2018. 60 Degrees Pharmaceuticals, Inc. also collaborates with prominent research organizations in the U.S., Australia, and Singapore. The 60 Degrees Pharmaceuticals, Inc. mission has been supported through in-kind funding from the U.S. Department of Defense and private institutional investors including Knight Therapeutics Inc., a Canadian-based pan-American specialty pharmaceutical company. 60 Degrees Pharmaceuticals, Inc. is headquartered in Washington D.C., with a majority-owned subsidiary in Australia. Learn more at . Cautionary Note Regarding Forward-Looking Statements This press release may contain “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward‐looking statements reflect the current view about future events. When used in this press release, the words “anticipate,” “believe,” “estimate,” “expect,” “future,” “intend,” “plan,” or the negative of these terms and similar expressions, as they relate to us or our management, identify forward‐looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy, activities of regulators and future regulations and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: there is substantial doubt as to our ability to continue on a going-concern basis; we might not be eligible for Australian government research and development tax rebates; if we are not able to successfully develop, obtain FDA approval for, and provide for the commercialization of non-malaria prevention indications for tafenoquine (ARAKODA® or other regimen) or Celgosivir in a timely manner, we may not be able to expand our business operations; we may not be able to successfully conduct planned clinical trials; and we have no manufacturing capacity which puts us at risk of lengthy and costly delays of bringing our products to market. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company’s filings with the Securities and Exchange Commission (SEC), including the information contained in our Annual Report on Form 10-K filed with the SEC on April 1, 2024, and our subsequent SEC filings. Investors and security holders are urged to read these documents free of charge on the SEC’s web site at As a result of these matters, changes in facts, assumptions not being realized or other circumstances, the Company’s actual results may differ materially from the expected results discussed in the forward-looking statements contained in this press release. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Media Contact: Sheila A. Burke SheilaBurke-consultant@60degreespharma.com (484) 667-6330 Investor Contact: Patrick Gaynes patrickgaynes@60degreespharma.com (310) 989-5666

DHFR, or dihydrofolate reductase, plays a crucial role in the human body as an enzyme involved in the synthesis of DNA, RNA, and amino acids. It catalyzes the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF), a vital coenzyme required for the production of nucleotides. THF is essential for cell division, growth, and repair, making DHFR an important target for pharmaceutical interventions. Inhibition of DHFR activity can disrupt the folate metabolism pathway, leading to impaired DNA synthesis and cell proliferation. Consequently, DHFR inhibitors are widely used in chemotherapy to treat cancer and other diseases characterized by excessive cell growth. In cancer treatment, a good and effective DHFR inhibitor should not only possess a strong affinity with reductase but also be highly specifically taken up by transport proteins. The binding capability of these compounds with DHFR may slightly decrease. However, their affinity with the RFC transport protein is enhanced, enabling them to inhibit tumor growth equivalently as Methotrexate. The efficient binding of RFC transport protein with its folic acid analogs presents new prospects for tumor treatment. Malignant cells would overexpress RFC transport protein to ensure their continuously growing demand for folic acid is met. Apart from serving as chemotherapeutic drugs for tumors, anti-folate inhibitors such as Methoxybenzylpyrimidine27.19 exhibit antibacterial activity due to their capability of directly inhibiting the corresponding bacterial reductase. The analysis of the target DHFR reveals a competitive landscape with multiple companies actively developing drugs. Pfizer Inc., medac Gesellschaft für klinische Spezialpräparate mbH, Sunflower Pharmaceutical Group Co., Ltd., and Spectrum Pharmaceuticals, Inc. are the companies growing fastest under this target. The highest stage of development for the target DHFR is the approved phase, with small molecule drugs being the most rapidly progressing drug type. The approved indications for drugs targeting DHFR include Malaria, Urinary Tract Infections, Bacterial Infections, and several others. China is the country with the fastest development under the target DHFR, followed by the United States, the European Union, and Japan. The future development of the target DHFR is expected to continue with a focus on small molecule drugs and expanding indications. Unveiling DHFR Inhibitors: A Potent Weapon in Treating Cancer and Microbial InfectionsDHFR inhibitors are a type of medication or compound that specifically target and inhibit the activity of dihydrofolate reductase (DHFR). DHFR is an enzyme that plays a crucial role in the synthesis of DNA, RNA, and proteins by catalyzing the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF), which is an essential cofactor in these biological processes. From a biomedical perspective, DHFR inhibitors are commonly used in the treatment of various diseases, particularly cancer and microbial infections. By inhibiting DHFR, these inhibitors disrupt the production of THF, leading to a depletion of folate levels in cells. Since folate is necessary for the synthesis of nucleotides, which are building blocks of DNA and RNA, inhibiting DHFR effectively impairs the growth and proliferation of cancer cells or pathogenic microorganisms. DHFR inhibitors can be classified into different types based on their chemical structures and mechanisms of action. Some examples include methotrexate, trimethoprim, and pyrimethamine. These inhibitors are often used in combination with other drugs or therapies to enhance their effectiveness and minimize the development of drug resistance. It is important to note that DHFR inhibitors may have side effects, and their usage should be carefully monitored by healthcare professionals. Additionally, the specific indications and dosages of DHFR inhibitors may vary depending on the disease being treated and the patient's individual characteristics. List of DHFR InhibitorsThe currently marketed DHFR inhibitors include: PralatrexatePemetrexed Disodium HydrateChloroquine Phosphate/Proguanil HydrochlorideAtovaquone/Proguanil HydrochlorideBrodimoprimGentamicin Sulfate/TrimethoprimSulfamethoxazole/Sulfadiazine/TrimethoprimCefalexin/TrimethoprimPyrimethamine/SulfadoxineTrimethoprim HydrochlorideFor more information, please click on the image below. What are DHFR inhibitors used for?DHFR inhibitors have strong potential in addressing bacterial infections and breast cancer.For more information, please click on the image below to log in and search. How to obtain the latest development progress of DHFR inhibitors?In the Synapse database, you can keep abreast of the latest research and development advances of DHFR inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!