MTNR1A x MTNR1B

With the year’s first two biotech IPOs raised – and upsized – another pair of hopefuls have set terms for their offerings, albeit with more modest targets. Alto Neuroscience and Fractyl Health both filed to raise just over $100 million on Monday.Cancer therapy developers CG Oncology and ArriVent set a high bar with their public debuts last week, raising $380 million and $175 million, respectively.  Alto’s depression portfolioAlto is aiming to sell 6.7 million shares at $14-$16 a piece. At the midpoint, the behaviour disorder company would raise $100.5 million and be valued at $363.4 million. While the IPO boom years of 2020 and 2021 saw several preclinical companies go public, the two-year downturn has whetted appetites for companies with more late-stage products, and Alto fits that bill with five central nervous system (CNS) programmes in the clinic.Alto’s lead candidates are in Phase IIb testing for major depressive disorder (MDD), and enrollment in each trial was guided by biomarkers: for ALTO-100, which targets brain-derived neurotrophic factor (BDNF), the company used a cognitive biomarker, while an electroencephalography biomarker was leveraged for ALTO-330. The compound dually targets melatonin receptor 1/2 (MT1/2) and 5-hydroxytryptamine 2C (5-HT2C). Both candidates posted positive data last year. Fresh topline data for ALTO-100 and ALTO-300 are expected in the second half of 2024 and the first half of 2025, respectively.Alto also plans to start Phase II studies of two additional programmes this half. ALTO-101 is phosphodiesterase-4 (PDE4) inhibitor in development for cognitive impairment associated with schizophrenia; ALTO-203 is histamine H3 receptor antagonist intended to treat people with MDD and higher levels of anhedonia.Fractyl eyes obesity opportunityAfter initially joining the IPO queue in December, Fractyl is now looking to sell 7.3 million shares at a range of $14-$16. If the offering prices at the midpoint, the metabolic disease company would raise $110 million and earn a market capitalisation of $714.1 million. Following the success of GLP-1 agonists for both diabetes and weight loss, Fractyl’s pipeline features two products in the disease space with unique modalities.  Revita, the company’s lead product, is an outpatient procedural therapy involving hydrothermal ablation of the duodenal mucosa to improve a patient’s metabolic function. This half, Fractyl plans to start a trial of Revita as a weight maintenance therapy in patients who responded to a GLP-1 treatment but wish to discontinue without weight regain. The company is also enrolling patients with inadequately controlled type 2 diabetes to receive Revita in the pivotal Revitalize-1 study, with topline data expected in the fourth quarter.Fractyl’s second programme is Rejuva, an adeno-associated virus (AAV) vector-based GLP-1 pancreatic gene therapy that’s slated to enter the clinic in 2025.