Saphorix Pharma: Novel Frst-choice Last-resort Antibiotics

Background

A growing number of patients suffer from hospitalization-requiring methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) infections that are resistant to first-line and second-line treatments.

For these patients, doctors can choose (freely) from a small selection of last-resort antibiotics such as vancomycin (MRSA only), daptomycin or linezolid.

At this point, patients are typically weak, and many have comorbidities or are on other medications that the doctor must take into account when selecting the last-resort antibiotic. Unfortunately, current last-resort treatments are associated with acute or chronic adverse side effects, making the doctor’s decision complex.

Newer antibiotics suffer from safety‑related drawbacks, and hence, doctors have no reason to prescribe them ahead of the older medicines. So, doctors have no reason to deviate from good AMR stewardship and will still preferentially prescribe the older drugs.

A new safe‑for‑all choice is much needed:

• Patients desperately need a safer treatment
• Drug developers need certainty that their new drug will be prescribed, and safety is the key to that.

Technology Overview

The research team are developing a new class of antibiotics, Triaromatic Pleuromutilins (TAPs), that combine potent activity against the multi-resistant bacteria MRSA and VRE with a superior safety profile.

The TAPs thereby address a critical need and gap in the current last‑resort arsenal, which is often toxic, especially to elderly and other vulnerable patient groups.

TAPs are very safe, and the preliminary data indicate a better safety and tolerability profile than current last-resort antibiotics.

The only other pleuromutilin in the clinic is lefamulin (not approved for MRSA), which is well tolerated, but carries a dose‑limiting and, for some patients, counter‑indicating risk for QT‑prolongation.

Importantly, TAPs show low potential for QT prolongation, and results from other safety‑related studies to date demonstrate a great potential for excellent tolerability, making TAPs a future first‑choice last‑resort MRSA treatment.

The current lead compound (10) has already been successfully validated and optimized:

• Antibacterial activity: The lead compound (10) shows good antibacterial activity against a spectrum of virulent pathogens.
• Solubility: The lead compound (10) is highly soluble.
• Safety: The lead compound (10) shows no hERG or P‑gp safety concerns and the cytotoxicity analysis for the TAPs was also positive.

Stage of Development

The lead compound has been extensively evaluated and validated for its in vitro drug-like properties (solubility, P-gp inhibition, CYP3A4 inhibition, Caco-2 permeability, hERG inhibition, plasma protein binding, MIC, bacterial time-kill and cytotoxicity).

The research team have studied PK in mice, rats and pigs, with performance similar to lefamulin. In addition, the research team have improved bioavailability 6-fold in rats via an ASD formulation (18%). Lastly, they have evaluated efficacy against S. aureus and VRE, showcasing antibacterial performance equal to that of vancomycin (S. aureus), lefamulin and linezolid (VRE).

Benefits

• Safe and effective (large data pack available on request), in vitro and in vivo
• Pleuromutilins have inherent advantages over many other antibiotics:
  • Unique mechanism of action (low cross-resistance)
  • Slow onset of resistance (a TAP will remain clinically relevant for a long period)
• TAPs have the potential to be developed for oral and IV administration

With over 200 compounds synthesized via Click Chemistry and two strong preclinical candidates identified (CVH-174 and CVH-276), TAPs are positioned to become the go-to option in a $8 billion anti-MRSA market — a market projected to double within a decade.

IP is secured in the US, EU, CH, AUS and CA, the team is experienced, and the research team are now seeking investment to complete IND-enabling studies and bring this safer and sought-after antibiotic to patients in need.

Applications

Use case:

Favorable last‑resort treatment for MRSA infections in weak or vulnerable patients.

Market size:

At the moment, in North America, Europe and Australia alone, approximately 1 million patients each year require a last-resort antibiotic to treat their MRSA or VRE infection. Worldwide, that number is much higher.

As resistance rates increase, sales of last-resort antibiotics have been projected to more than double within the next 10 years.

Hence, by the time one of the research team’s TAPs reaches the market, more patients will need a last-resort antibiotic, but the rate of bacterial infections that are resistant towards older drugs like vancomycin or daptomycin will also have increased, adding further reason for doctors to choose a TAP over other options.

In conclusion, the estimated total addressable market by 2034 will be between 1 and 2 million annual patients, which will also continue to increase for a number of years.

Opportunity

The research team aim to spin out a company, Saphorix Pharma, in 2026 to develop this asset through the early clinical phases.

• Saphorix Pharma Pitch Deck

The team are looking for investors to support the next stages of development, and for pharma companies interested in collaborating.