Malaria, Vivax

HDT Bio’s LION ™ platform to support malaria vaccine development by MalarVx SEATTLE, WA, USA I January 15, 2025 I MalarVx, Inc., a clinical-stage vaccine company, is proud to announce a license to HDT Bio’s proprietary self-amplifying replicon RNA (repRNA) and lipid nanoparticle (LION™) technologies for use in malaria vaccines. In addition to HDT Bio’s technologies, the agreement provides MalarVx additional support from HDT to develop and commercialize malaria vaccines. This license expands the long-standing relationship between the parties. Malaria was responsible for 597,000 deaths and 263 million cases in 2023, according to the World Health Organization. Despite the expenditure of $4 billion per year on control 1 , malaria deaths and cases have not substantively changed over the last decade. Consequently, a safe, effective, long-lasting, easy-to-use, and cost-effective vaccine to prevent malaria is desperately needed. HDT Bio Corp. is a clinical-stage biopharmaceutical company specializing in advanced RNA vaccine technologies, including the company’s proprietary LION nanoparticle delivery system. LION is well-suited for use in vaccines to prevent viral and bacterial infections. “We are excited to contribute our expertise in RNA vaccine technologies in an effort to develop malaria vaccines with MalarVx,” said Steve Reed, Ph.D., CEO of HDT Bio. “Our LION platform has a demonstrated ability to rapidly generate potent, durable immune responses with a favorable safety profile.” “This collaboration is an example of our aspiration to enable a new generation of global health technologies,” said Curt Malloy, HDT SVP Strategic Operations.  “We are dedicated to applying our technology to address critical global health challenges. From combating infectious diseases like malaria to pioneering breakthroughs in cancer prevention and treatment, we remain committed to catalyzing innovations that address unmet global health needs.” MalarVx has also demonstrated the potential of LION-based vaccines to prevent infections caused by Plasmodium parasites, the pathogens responsible for malaria in humans and other animals. “We believe the attributes of LION-based vaccines, including increased potency, product stability, and simplified manufacturing, are essential for vaccines designed for use in resource limited environments,” said James Davie, MalarVx CEO. “Of particular interest is the potential for a multi-species vaccine capable of preventing Plasmodium falciparum and Plasmodium vivax infections, since these pathogens are responsible for most cases of malaria in humans.” Dr. Marion Avril, Ph.D., MalarVx Program Director, added, “We recognize the transformative potential of our vaccines to combat one of humanity’s most devastating diseases. Our collaboration with HDT Bio is a significant step towards achieving a world free from malaria. Together, we are committed to advancing innovative solutions that will save lives and improve health outcomes for millions of people globally.” About MalarVx MalarVx is a Seattle-based clinical-stage biopharmaceutical company developing vaccines to prevent malaria. Current efforts focus on the clinical development of a replicon RNA-based vaccine for the prevention of Plasmodium falciparum infection and on culturing the mosquito stages of the parasite for the cost-effective production of whole organism vaccines. For more information on MalarVx and its work on safe and effective malaria vaccines, visit www.malarvx.com About HDT Bio HDT Bio is a Seattle-based, clinical-stage biopharmaceutical development company. With core technology and expertise in nucleic acid formulation, the company develops products that seek to harness host-directed immune responses. HDT Bio’s work focuses on infectious disease and oncology vaccines and therapeutics through early-stage collaborations with partners worldwide. The company’s vaccine platforms combine formulation and adjuvant ingredients to stabilize and deliver RNA to the immune system to stimulate responses. HDT Bio’s repRNA/LION™ was the first self-amplifying RNA vaccine platform to receive regulatory authorization. For more information on HDT Bio platforms, visit www.hdt.bio 1 “Malaria Cases Up Again in 2023, African Children Worst Hit, WHO Reports.” Reuters, December 11, 2024. https://www.reuters.com/business/healthcare-pharmaceuticals/malaria-cases-up-again-2023-african-children-worst-hit-who-reports-2024-12-11/ . SOURCE: MalarVx; HDT Bio

LONDON, UK I December 04, 2024 I GSK plc (LSE/NYSE: GSK) and Medicines for Malaria Venture (MMV) announced today that the World Health Organization (WHO) has awarded prequalification to tafenoquine , the first single-dose medicine for the prevention of relapse of Plasmodium vivax (P. vivax) malaria. Tafenoquine , co-administered with chloroquine, is now also included in WHO’s updated Guidelines for malaria, in South America, marking the first time the medicine has been recommended by WHO. This milestone is a significant step toward closing the treatment gap for P. vivax malaria. The WHO prequalification and updated guidelines include both adults and children aged 2 years and older, weighing at least 10 kg. A single-dose medicine provides an opportunity to overcome challenges with adherence to the existing longer, one-two week regimen of the standard of care, which can be a challenge for patients with relapsing malaria whose symptoms improve shortly after treatment initiation 1 . P. vivax is the dominant malaria parasite in most countries outside of sub-Saharan Africa, prevalent in most tropical and sub-tropical areas in the world, with children under five and migrant populations at particular risk. Among these vulnerable groups, infants and children carry a disproportionate burden, being highly vulnerable to severe disease, recurrence and anaemia 2 . The complex lifecycle of the P. vivax parasite includes a blood stage and an undetectable dormant liver stage, which can reactivate, causing repeated episodes of malaria following a single infectious bite of a mosquito carrying this parasite. Thomas Breuer, Chief Global Health Officer, GSK, said: “WHO prequalification of tafenoquine opens new possibilities to positively impact and protect more lives; lives of children and vulnerable populations who continue to bear the burden of this devastating disease. Inclusion of tafenoquine in the updated Guidelines for malaria is an equally important step forward in efforts to eliminate this preventable and treatable disease. Making treatments simpler for people to take is an ambition of ours across much of our Global Health pipeline and portfolio. Alongside our partners, we remain committed to enabling affordable and equitable access to this new single-dose treatment option for those in need in malaria-endemic countries.” Martin Fitchet, Chief Executive Officer, MMV, said: “Today marks a historic milestone in the fight against malaria. The WHO’s prequalification of tafenoquine and its inclusion in the updated Guidelines for malaria is a groundbreaking advancement on the road to elimination, which will transform lives by providing a well-tolerated, effective, and single-dose cure to prevent malaria relapses in some of the world’s most vulnerable communities. This achievement is a testament to the power of innovation and collaboration in global health, to bring us closer to our vision of a malaria-free world.” Tafenoquine , an 8-aminoquinoline antimalarial drug targeting the liver-stage of P. vivax malaria, is recommended as an alternative to primaquine (3.5 mg/kg total dose) for preventing malaria relapses in children over the age of two in South America. A single dose of tafenoquine administered to P. vivax patients who receive chloroquine treatment provides what is known as radical cure: the treatment of both the blood- and liver-stages of the disease. Tafenoquine , like all 8-aminoquinolines, has the potential to cause haemolytic anaemia in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, therefore G6PD testing must be performed before prescribing. This is possible with the ‘STANDARD’ G6PD test, developed in collaboration between SD Biosensor and PATH, which provides a measure of a patient’s G6PD enzyme activity levels in two minutes based on a drop of blood from a finger-prick. WHO prequalification of medicines is crucial as it ensures that the medicine meets standards of quality, safety and efficacy, and is suitable for the target population. The prequalification programme has played a vital role in improving the access to life-saving medications used by millions in low- and middle-income countries. The WHO Guidelines for malaria are regularly reviewed and updated by the world’s leading malaria experts under WHO’s convening. This update includes a first recommendation for tafenoquine (150mg tablets and 50mg dispersible tablets) with chloroquine in South America. WHO prequalification and Guideline inclusion follows the launch of tafenoquine in Brazil and Thailand in June this year. Approvals for tafenoquine have been granted in Australia, Brazil, Colombia, Ethiopia, Guyana, Myanmar, Pakistan, Peru, the Philippines, Thailand, Vietnam and the United States, and the drug is undergoing marketing authorisation evaluation in a number of other countries where P. vivax is endemic. About tafenoquine Tafenoquine is an 8-aminoquinoline with activity against all stages of the P. vivax lifecycle, including hypnozoites. It was first synthesised by scientists at the Walter Reed Army Institute of Research in 1978. GSK’s legacy in the research and development of tafenoquine as a potential medicine for malaria commenced over 20 years ago.  In 2008, GSK entered into a collaboration with the not-for-profit drug research partnership, MMV, to develop tafenoquine as an anti-relapse medicine for patients infected with P. vivax . The tafenoquine clinical programme is part of GSK’s global health programme aimed at improving healthcare for vulnerable populations. About Standard G6PD test The STANDARD G6PD test was developed in collaboration between SD Biosensor and PATH. The handheld device provides a measure of a patient’s G6PD enzyme activity levels in two minutes based on a drop of blood from a finger-prick. The Test has been approved by the Australian TGA, and by the Global Fund Expert Review Panel on Diagnostics (ERPD) and is distributed to over 30 countries. Important safety information Tafenoquine can cause haemolytic anaemia in patients with G6PD deficiency. The most common side effects are difficulty sleeping, headache, dizziness, nausea and vomiting. Allergic hypersensitivity reactions can occur after taking the drug. Please refer to the Consumer Medicine Information (CMI) summary for important dosage, administration, and safety information available at this link: kozenis-cmi-au.pdf (gsk.com) About Plasmodium vivax malaria The Plasmodium parasite is a complex organism with a lifecycle spanning both humans and mosquitoes. After an infected mosquito bite, the P. vivax parasite infects the blood and causes an acute malaria episode. It also has the ability to lie dormant in the liver (in a form known as hypnozoite) from where it periodically reactivates to cause relapses of P. vivax malaria. Hence, a single P. vivax infection can give rise to multiple episodes of malaria, in the absence of a new mosquito bite. These relapses can occur weeks, months or even years after the initial infection. The dormant liver forms of the parasite cannot be readily treated with most anti-malarial treatments active against the blood-stage parasite. The current treatment (primaquine) for the dormant liver stage must be taken for 7 to 14 days to be effective, a regimen that is associated with poor compliance in unsupervised patients 3,4,5 . The use of a medicine that targets the dormant liver forms of the parasite, co-administered with a medicine to treat the blood stage, is known as radical cure. P. vivax malaria has a significant public health and economic impact, primarily in South-Asia, South-East Asia, Latin America and the horn of Africa. The disease is estimated to cause around 8.5 million clinical infections every year. The clinical features of P. vivax malaria include fever, chills, vomiting, malaise, headache and muscle pain, and in some cases, can lead to severe malaria and be fatal. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. About Medicines for Malaria Venture MMV is a Swiss-based not-for-profit organization working to deliver a portfolio of accessible medicines with the power to treat, prevent and eliminate malaria. Born in 1999, out of a need for greater health equity, we close critical gaps in research, development and access – working “end-to-end” to expand the use of existing antimalarials and innovate new compounds to protect public health. This starts with women and children. It’s working. As of 2023, MMV-supported products have effectively treated an estimated 680 million people and saved around 15.4 million lives. We cannot stop now. With a quarter of a billion malaria cases and more than 600,000 deaths reported in 2022, progress towards disease elimination has stalled. MMV is part of an ecosystem of partners determined to change this. Bringing public and private sector partners together, we pioneer new solutions that align with local and global health priorities and promote the equitable development of effective and affordable products that work to help end malaria and advance health for all. For more information, visit http://www.mmv.org . References SOURCE: GlaxoSmithKline

University of Kentucky will commence a Phase IIb clinical study of drug development candidate SJ733 for treatment of vivax malaria.SJ733 will be combined with a single dose of tafenoquine in the study.The right of reference allows FDA to review 60 Degrees Pharma’s regulatory file when the agency evaluates new study protocols for the SJ733-tafenoquine Phase IIb program. WASHINGTON, Aug. 12, 2024 (GLOBE NEWSWIRE) -- 60 Degrees Pharmaceuticals, Inc. (NASDAQ: SXTP; SXTPW) (the “Company” or “60 Degrees Pharma”), a pharmaceutical company focused on developing new medicines for infectious diseases, announced today that it has granted the University of Kentucky a right of reference to the Company’s new drug application (“NDA”) for ARAKODA® (tafenoquine). ARAKODA is the Company’s anti-malarial approved by the U.S. Food and Drug Administration (“FDA”) in 2018, indicated for the prophylaxis of malaria in patients aged 18 years of age and older. The right of reference will allow FDA to review clinical efficacy and safety data, non-clinical data, and chemistry, manufacturing and control information on ARAKODA as the agency reviews protocols and new Investigational New Drug (“IND”) application submissions related to the University of Kentucky’s investigational SJ733 Phase IIb program. SJ733 is an oral ATP4 inhibitor of Plasmodium, which has been shown to have a favorable safety profile and rapid anti-parasitic effect. The Phase IIb study being conducted by the University of Kentucky and Eisai Co. Ltd. (“Eisai”) will combine SJ733 with tafenoquine – the active ingredient in ARAKODA – to evaluate the safety, tolerability, and pharmacokinetics of a single-dose combination of the two drugs. The trial is funded by the Global Health Innovative Technology Fund. The current state-of-the-art treatment for vivax malaria is a combination of tafenoquine and chloroquine administered over three days; however, resistance of P. vivax to chloroquine is widespread in some parts of the world. “Innovations in treating P. vivax malaria, which infects an estimated 14 million people a year, have been limited in recent decades,” said Dr. R. Kip Guy, principal investigator on the Phase IIb study, and Professor and Dean of the University of Kentucky College of Pharmacy. “The upcoming study of SJ733 combined with tafenoquine has the potential to pave the way for very meaningful improvement in malaria treatment around the world.” 60 Degrees Pharma will supply tafenoquine and placebos as study drugs in the University of Kentucky Phase IIb trial. 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. About the SJ733 Phase IIb Clinical Trial at University of Kentucky The overall objective of the Phase IIb study is to examine the clinical safety and efficacy of the combination of SJ733 and TQ for radical cure of P. uncomplicated P. vivax malaria in adults with a 1, 2, or 3-day schedule of the SJ733-tafenoquine combination. The purpose is to develop an SJ733-TQ combination drug suitable for treatment of all patients with uncomplicated P. vivax malaria. The targeted results for this study are data that support 1 to 3 doses of an SJ733-TQ fixed-dose combination for radical cure of P. vivax mono-infected patients. This will set the stage for subsequent pivotal Phase 3 studies. SJ733 is a PfATP4 inhibitor that meets criteria for treatment of uncomplicated malaria. Three clinical trials of SJ733 have been completed. Phase I examined safety and pharmacokinetics of SJ733. Phase I tested pharmacodynamics in the human challenge model. Phase II (NCT04709692) determined the parasite reduction ratio, parasite reduction half-life and minimum inhibitory concentration of SJ733 in adults with uncomplicated malaria and assessed the exposure-response relationship (PK/PD). Current Phase Ia, Ib, and IIa human data show an excellent safety profile and tolerability, good oral availability, and moderate drug clearance. Eisai and the University of Kentucky have collaboratively designed the Phase IIb study and supportive non-clinical safety and pharmacokinetics studies, which will be contracted to rigorously qualified CROs and overseen by Eisai’s subject matter experts. Eisai will manage the manufacture of a new batch of SJ733 clinical trial material, as well as oversee conduct of the supportive non-clinical safety and pharmacokinetics studies. The University of Kentucky will oversee the regulatory filings to amend the current US-FDA IND (held by Professor Guy) for development of SJ733 and the Phase IIb clinical trial work, including the local ethics and regulatory submissions. About ARAKODA® (tafenoquine) Tafenoquine was discovered by Walter Reed Army Institute of Research. 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; orKnown 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 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 three 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 www.fda.gov/medwatch. The full prescribing information for 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 for 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 www.60degreespharma.com. The statements contained herein may include prospects, statements of future expectations and other forward-looking statements that are based on management’s current views and assumptions and involve known and unknown risks and uncertainties. Actual results, performance or events may differ materially from those expressed or implied in such forward-looking statements. 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 or patient recruitment in our trials might be slow or negligible; 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 website at www.sec.gov. 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. BurkeSheilaBurke-consultant@60degreespharma.com(484) 667-6330 Investor Contact:Patrick Gaynespatrickgaynes@60degreespharma.com(310) 989-5666 This press release was published by a CLEAR® Verified individual.