Half-life

• PAS-004 is being evaluated in a Phase 1 multicenter open label clinical trial ( NCT06299839 ) in patients with MAPK pathway driven advanced solid tumors with a documented RAS, NF1 or RAF mutation or patients who have failed BRAF/MEK inhibition.
• “Completion of the initial dosing of the first cohort of 3 subjects is a significant milestone in Pasithea’s mission towards developing PAS-004 as a potential best-in-class next-generation MEK inhibitor.
• PAS-004 is the first macrocyclic MEK inhibitor to enter human clinical trials, with an expected extended half-life which may provide better compliance rates, as well as improved efficacy in NF1.
• Macrocycles are known to exhibit stronger binding, better solubility and longer half-life with more selectivity and less off target effect as compared to acyclic small molecules.

• Mythic Therapeutics , a clinical-stage biotechnology company committed to the development of next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, today announced the publication of preclinical data highlighting the differentiating properties of its investigational cMET-targeting ADC, MYTX-011, in Molecular Cancer Therapeutics , a journal of the American Association for Cancer Research (AACR).
• “We believe that engineering pH-dependent binding could be a particularly compelling strategy for ADCs targeting medium to low levels of cMET expression in patients.
• A single dose of MYTX-011 showed at least three-fold higher efficacy than a benchmark ADC in mouse xenograft models of NSCLC ranging from low to high cMET expression.
• In a repeat dose toxicology study, MYTX-011 exhibited a toxicity profile similar to other MMAE-based ADCs.

• Ventus Therapeutics , a clinical-stage biopharmaceutical company utilizing its proprietary structural biology and computational chemistry platform, ReSOLVE™, to develop differentiated small molecule therapeutics, today announced results from its Phase 1 clinical trial of VENT-02, a novel, oral, brain-penetrant NLRP3 inhibitor.
• The Phase 1 trial evaluated the pharmacodynamics, pharmacokinetics, safety, and tolerability of VENT-02 across a broad range of single and multiple ascending doses in adult healthy volunteers.
• The moderate adverse events included headache and nausea and were only observed at a dose multiple times higher than the intended therapeutic doses.
• Based on the half-life and target coverage observed in the trial, VENT-02 has demonstrated the potential for once-daily dosing.

• Hundreds of thousands of people worldwide are taking drugs like Ozempic to lose weight.
• As demand for semaglutide increases, so are claims that taking it is “cheating” at weight loss or the “easy way out”.
• We don’t tell people who need statin medication to treat high cholesterol or drugs to manage high blood pressure they’re cheating or taking the easy way out.

How does it work?

• GLP-1 gets secreted by cells in your gut when it detects increased nutrient levels after eating.
• GLP-1 receptor agonist (GLP-1RA) medications like Ozempic help the body’s own GLP-1 work better by mimicking and extending its action.
• Read more:
  The rise of Ozempic: how surprise discoveries and lizard venom led to a new class of weight-loss drugs

What can users expect? What does the research say?

• Higher doses of semaglutide are prescribed to treat obesity compared to type 2 diabetes management (up to 2.4mg versus 2.0mg weekly).
• A large group of randomised controlled trials, called STEP trials, all tested weekly 2.4mg semaglutide injections versus different interventions or placebo drugs.
• Trials lasting 1.3–2 years consistently found weekly 2.4 mg semaglutide injections led to 6–12% greater weight loss compared to placebo or alternative interventions.

• Weight reduction due to semaglutide also leads to a reduction in systolic and diastolic blood pressure of about 4.8 mmHg and 2.5 mmHg respectively, a reduction in triglyceride levels (a type of blood fat) and improved physical function.
• Another recent trial in adults with pre-existing heart disease and obesity, but without type 2 diabetes, found adults receiving weekly 2.4mg semaglutide injections had a 20% lower risk of specific cardiovascular events, including having a non-fatal heart attack, a stroke or dying from cardiovascular disease, after three years follow-up.

Who is eligible for semaglutide?

• Australia’s regulator, the Therapeutic Goods Administration (TGA), has approved semaglutide, sold as Ozempic, for treating type 2 diabetes.
• The TGA has approved Wegovy to treat obesity but it’s not currently available in Australia.

What else do you need to do during Ozempic treatment?

• In addition to taking medication, people had brief lifestyle counselling sessions with dietitians or other health professionals every four weeks as a minimum in most trials.
• The aim of these trials was to show the effect of adding the medication on top of other lifestyle counselling.

A review of obesity medication trials found people reported they needed less cognitive behaviour training to help them stick with the reduced energy intake. This is one aspect where drug treatment may make adherence a little easier. Not feeling as hungry and having environmental food cues “switched off” may mean less support is required for goal-setting, self-monitoring food intake and avoiding things that trigger eating.

But what are the side effects?

• In on study these led to discontinuation of medication in 6% of people, but interestingly also in 3% of people taking placebos.
• More severe side-effects included gallbladder disease, acute pancreatitis, hypoglycaemia, acute kidney disease and injection site reactions.
• Here are some potential risks and benefits

  To reduce risk or severity of side-effects, medication doses are increased very slowly over months.

• Health, Meat and Livestock Australia, and Greater Charitable Foundation.
• She has consulted to SHINE Australia, Novo Nordisk, Quality Bakers, the Sax Institute, Dietitians Australia and the ABC.