December 5, 2019
As an oral, broad spectrum agent that preliminary data suggest is well-tolerated, SPR720 could afford us the opportunity to treat patients across their disease journey. Currently, approved treatments only exist for approximately 25% of NTM patients that are treatment refractory meaning they have failed all available treatment options and still suffer from the disease(1).
A major unmet need exists for the majority of NTM patients that are not treatment refractory. Recent FDA panels and industry correspondence as well as our discussion with KOLs highlight the need in NTM to improve a patient’s function and quality of life: early treatment mattersas it gives patients a chance to retain lung function and maintain quality of life. Patients that have suffered from refractory disease often have sustained progressive, permanent inflammatory lung damage that makes recovery and improvements in quality of life more challenging.
Source: Spero Investor Presentation, December 5, 2019
The properties of SPR720 and a review of data supporting prior advances in the field frame our opportunity for a more efficient development pathway. This pathway employs more efficient measures of patient benefit and more precise measurements of disease burden, ultimately assisting us in discovering the potential of our product candidates faster.
We plan to take a stepwise approach to developing new treatments for NTM patients, as is the case with HIV, TB, oncologic agents and other diseases treated with therapeutic combinations.
The next step is to show that these data translate to a positive biological effect in patients. Specifically, following our submission of an IND with the FDA and acceptance of that IND, we intend to assess in a Phase 2a clinical trial how SPR720 works on its own versus a placebo in patients. This is a standard first step in the development of new combination therapies, such as for TB and HIV. We plan to adapt this study design to allow early and efficient assessment of candidate drugs for the treatment of NTM lung disease. Should it be successful in Phase 2, SPR720 could potentially be the only novel agent that will have demonstrated microbiological activity as monotherapy, independent of ineffective and poorly tolerated background therapy.
Why do we have conviction that the Phase 2 design is appropriate and that positive results would be a meaningful advance for patients? Because clinical studies evaluating the therapeutic benefit of standard of care combination therapy, clarithromycin as a single agent, and inhaled amikacin all have demonstrated an early, measurable decrease in sputum bacterial burden (2, 3, 4, 5). Furthermore, these data support the long-term predictive power of early treatment response. Thus, among patients who demonstrated a decrease in sputum bacterial burden in response to the initiation of anti-NTM treatment, an early response was predictive of longer-term benefit. (1)
Source: David E. Grifﬁth, Jennifer Adjemian et al., American Journal of Respiratory and Critical Care Medicine
A successful result could follow the paradigm set by TB and HIV medicines and targeted oncologic therapy – response rate relative to placebo coupled with PK/tolerability/macrophage penetration would be evidence of SPR720’s therapeutic benefit relative to other agents in development and provide strong support for future development.
SPR720 is the only novel oral agent in clinical development for NTM and we look forward to advancing it into patients. We are inspired by the opportunity to help thousands of patients with NTM that still don’t have any new options, and we look forward to working with the patient community, clinicians, and our colleagues at the FDA as we build a Phase 2 clinical plan around these goals.
Chief Medical Officer of Spero Therapeutics