Trypanosomiasis

• The request seeks emergency access to the Company’s recently completed registration batches of PAX-101 (IV suramin) to address the critical shortage of medications required to combat the life-threatening sleeping sickness, also known as Trypanosoma brucei rhodesiense, Human African trypanosomiasis (TBr HAT), crisis in the region.
• Howard Weisman, Chairman and CEO of PaxMedica, emphasized the Company's dedication to providing immediate assistance in light of the urgent situation, stating: "The emergency request from the Ministry of Health of Malawi underscores the critical need for IV suramin to combat the continued devastating impact of sleeping sickness in the region.
• PaxMedica has worked diligently for many years to ensure access to this life-saving medication for those in need and today’s response to an urgent crisis strongly demonstrates our commitment to this mission."
• The decision comes in the wake of PaxMedica's recent completion of three pivotal registration/validation batches of PAX-101 ( PaxMedica - A Promising Path in Autism ), as part of its ongoing development program.

• Sanofi, DNDi and the HAT-r-ACC consortium announce the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive scientific opinion of Fexinidazole Winthrop as first oral treatment of acute form of sleeping sickness (rhodesiense).
• rhodesiense sleeping sickness, an acute and lethal form of this parasitic disease found in Eastern and Southern Africa.
• Sleeping sickness, or human African trypanosomiasis (HAT), is usually fatal without treatment.
• Both forms of sleeping sickness are transmitted by the bite of infected tsetse flies, which are found in 36 African countries.

• In April of this year, Spanish athlete Beatriz Flamini emerged into the light after a 500-day stay in a cave.
• Her descent underground is probably the longest undertaken by a long stretch.

The tick of life’s clocks

• Quite simply, because biological rhythms are at the heart of life, regulating it all the way from the molecular level up to that of the entire body.
• These include not only our sleep/wake cycles, but also body temperature, hormones, metabolism and the cardiovascular system, to name but a few.
• It may be associated with an increased risk of cancers in workers, prompting the WHO to label it as a probable carcinogen.

Genes: the great clockmakers

• A biological clock is a mechanism internal to organisms that, in the absence of an environmental signal, operates at its own frequency.
• The regular alternation of day and night has, for example, favoured the evolution of the circadian clock (circa, meaning “approximately”, and diem, “day”).
• The circadian clock mechanism was first discovered in the fruit fly, also known as Drosophila, in the 1970s.

An internal clock synchronised by the environment

• This is the deviation of an individual’s internal rhythm from the time of the time zone they are in.
• Environmental signals in general, and light in particular, help to re-synchronise the individual: light perceived at the end of the night moves the clock forward, while light perceived at the beginning of the night delays it.
• In humans, light is not perceived directly by the molecular clock, but is captured in the retina and then transmitted via the retino-hypothalamic pathway to a central clock, where it modulates the synthesis of clock proteins.

Other times, other clocks

• This seasonality is generally dictated by several factors, including by what is known as a circannual clock in the case of many species.
• The clock mechanisms in marine species are also unknown, partly because of the oceans’ complex temporal structure.
• For example, many corals synchronise their reproduction, laying eggs once a year over a very short period of time.
• Our work underlines that the temporal coordination in physiology is likely critical, even in the most extreme life environments such as the deep ocean.

• TARRYTOWN, NY, Feb. 15, 2023 (GLOBE NEWSWIRE) -- via NewMediaWire – PaxMedica, Inc. (Nasdaq: PXMD), a clinical stage biopharmaceutical company focusing on the development of novel anti-purinergic drug therapies (“APT”) for the treatment of disorders with intractable neurologic symptoms, today released a 2022 shareholder letter discussing its recent accomplishments and upcoming milestones.
• 2022 was an exciting year for PaxMedica.
• The past year was highlighted by our transition to a public company, after our Initial Public Offering (IPO) in August 2022.
• As you can see, PaxMedica made great strides in 2022 and we’re poised to achieve a number of additional milestones over the next 12-24 months.