Spero Therapeutics Announces Presentation of SPR719 (Active Moiety of SPR720) In Vitro Data Demonstrating Low Propensity for the Development of Resistance at IDWeek 2024
Spero Therapeutics announced a poster presentation at IDWeek 2024 showcasing in vitro data on SPR719, the active moiety of SPR720, for treating nontuberculous mycobacterium pulmonary disease (NTM-PD). The study, conducted with Microbiologics, revealed:
1. SPR719's low propensity for resistance development in MAC NTM-PD strains, both alone and combined with standard care antibiotics.
2. High potency against macrolide susceptible and resistant MAC strains.
3. Mutation frequencies about 3 orders of magnitude lower than standard of care comparators.
4. No antagonism when combined with clarithromycin or ethambutol.
These findings highlight SPR720's potential for prolonged combination regimens in NTM-PD treatment.
Spero Therapeutics ha annunciato una presentazione di poster all'IDWeek 2024 che mostra dati in vitro su SPR719, il principio attivo di SPR720, per il trattamento della malattia polmonare da micobatteri non tubercolari (NTM-PD). Lo studio, condotto con Microbiologics, ha rivelato:
1. La bassa propensione allo sviluppo di resistenza di SPR719 nei ceppi di MAC NTM-PD, sia da solo che combinato con antibiotici standard.
2. La elevata potenza contro ceppi MAC sensibili e resistenti ai macrolidi.
3. Frequenze di mutazione circa 3 ordini di grandezza inferiori rispetto ai comparatori di cura standard.
4. Nessun antagonismo quando combinato con claritromicina o etambutolo.
Questi risultati evidenziano il potenziale di SPR720 per regimi combinati prolungati nel trattamento della NTM-PD.
Spero Therapeutics anunció una presentación de póster en IDWeek 2024 que muestra datos in vitro sobre SPR719, el principio activo de SPR720, para el tratamiento de la enfermedad pulmonar por micobacterias no tuberculosas (NTM-PD). El estudio, realizado con Microbiologics, reveló:
1. La baja propensión al desarrollo de resistencia de SPR719 en cepas de MAC NTM-PD, tanto sola como combinada con antibióticos de atención estándar.
2. Alta potencia contra cepas de MAC susceptibles y resistentes a macrólidos.
3. Frecuencias de mutación aproximadamente 3 órdenes de magnitud más bajas que los comparadores de atención estándar.
4. Ningún antagonismo cuando se combinó con claritromicina o etambutol.
Estos hallazgos destacan el potencial de SPR720 para regímenes combinados prolongados en el tratamiento de NTM-PD.
Spero Therapeutics는 IDWeek 2024에서 시험관 내 데이터를 공개하며 SPR719, SPR720의 활성 물질을 사용한 비결핵성 마이코박테리아 폐 질환 (NTM-PD) 치료 관련 포스터 발표를 했습니다. Microbiologics와 함께 진행된 연구 결과는 다음과 같습니다:
1. SPR719의 저항성 개발에 대한 낮은 경향은 MAC NTM-PD 균주에서, 단독으로 또는 표준 치료 항생제와 함께 사용할 때 발견되었습니다.
2. 맥롤라이드에 대한 저항성과 민감한 MAC 균주에 대해 높은 효능.
3. 돌연변이 빈도는 표준 치료 비교군보다 약 3배 낮았습니다.
4. 클라리트로마이신이나 에탐부톨과 결합했을 때 길항작용이 없었습니다.
이러한 결과는 NTM-PD 치료에서 SPR720의 오랜 조합 요법의 잠재력을 강조합니다.
Spero Therapeutics a annoncé une présentation d'affiche lors de l'IDWeek 2024 mettant en avant des données in vitro sur SPR719, le principe actif de SPR720, pour le traitement de la maladie pulmonaire à mycobactéries non tuberculeuses (NTM-PD). L'étude, réalisée avec Microbiologics, a révélé :
1. La faible propension à développer des résistances de SPR719 dans les souches de MAC NTM-PD, tant seules qu'en combinaison avec des antibiotiques de soin standards.
2. Une grande puissance contre les souches de MAC sensibles et résistantes aux macrolides.
3. Des fréquences de mutation environ 3 ordres de grandeur inférieures à celles des comparateurs de soins standards.
4. Aucun antagonisme lorsqu'il est combiné avec la clarithromycine ou l'éthambutol.
Ces résultats soulignent le potentiel de SPR720 pour des régimes combinés prolongés dans le traitement de la NTM-PD.
Spero Therapeutics gab eine Posterpräsentation auf der IDWeek 2024 bekannt, die in vitro Daten zu SPR719, dem aktiven Bestandteil von SPR720, zur Behandlung der nichttuberkulösen Mykobakterien-Lungenkrankheit (NTM-PD) präsentiert. Die Studie, die in Zusammenarbeit mit Microbiologics durchgeführt wurde, ergab:
1. SPR719 hat eine geringe Neigung zur Entwicklung von Resistenzen in MAC NTM-PD-Stämmen, sowohl allein als auch in Kombination mit Standard-Antibiotika.
2. Hohe Wirksamkeit gegen sowohl makrolidempfindliche als auch resistente MAC-Stämme.
3. Mutationshäufigkeiten, die etwa um 3 Größenordnungen niedriger sind als die der Standardvergleichsmedikamente.
4. Kein Antagonismus bei der Kombination mit Clarithromycin oder Ethambutol.
Diese Ergebnisse unterstreichen das Potenzial von SPR720 für verlängerte Kombinationstherapien bei der Behandlung von NTM-PD.
- SPR719 showed low propensity for resistance development in NTM-PD MAC strains
- High potency demonstrated against both macrolide susceptible and resistant MAC strains (MIC values of 2 ug/mL)
- Mutation frequencies for SPR719 were about 3 orders of magnitude lower than standard of care comparators
- No antagonism observed when SPR719 was combined with clarithromycin or ethambutol
- None.
Insights
This study on SPR719, the active moiety of SPR720, provides promising insights for the treatment of nontuberculous mycobacterium pulmonary disease (NTM-PD). The key findings demonstrate:
- SPR719 shows a low propensity for resistance development against MAC strains, with mutation frequencies 3 orders of magnitude lower than standard of care (SOC) antibiotics.
- High potency against both macrolide-susceptible and resistant MAC strains, with MIC values of
2 ug/mL . - No antagonism when combined with current SOC antibiotics, suggesting potential for use in prolonged combination regimens.
These results are particularly significant for NTM-PD treatment, which typically requires extended antibiotic courses. The low resistance development and compatibility with SOC antibiotics could potentially improve treatment outcomes and reduce the risk of treatment failure due to resistance. However, it's important to note that these are in vitro results and clinical trials will be necessary to confirm these benefits in patients. For investors, this data strengthens SPR720's potential in the NTM-PD market, but commercialization is still likely years away.
In vitro data on SPR719 show low propensity for resistance development in NTM-PD MAC strains when administered as a single agent and in combination with standard of care agents
Study highlighting SPR720 potential benefits for prolonged combination regimens typical to NTM-PD treatment
CAMBRIDGE, Mass., Oct. 16, 2024 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company, focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, today announced a poster presentation at IDWeek 2024, entitled “Evaluation of the Spontaneous Mutation Frequencies of SPR719 Alone and in Combination with Other Agents Used to Treat Mycobacterium avium Complex Pulmonary Disease.” The poster will be presented on Friday, October 18, 2024, in Hall J & K, at 12:15 PM - 1:30 PM Pacific Time. A copy of the poster will be available on the Spero corporate website here.
SPR720 is an oral, chemically stable phosphate ester prodrug that is converted rapidly in vivo to SPR719, the active moiety. SPR719 targets the ATPase site of DNA gyrase B in mycobacteria, a mechanism that is distinct from that of other antibiotics in use for nontuberculous mycobacterium pulmonary disease (NTM-PD).
The study was conducted in collaboration with Microbiologics, a leading contract research and manufacturing organization (CRMO), partnering with pharmaceutical and diagnostic companies to bring new lifesaving technology, anti-infective drugs, vaccines and therapeutics to market.
“These in vitro results present an important aspect of SPR719’s activity against MAC NTM-PD,” said Chris Pillar, Ph.D., Director of Science and Operations, Microbiologics. “Resistance to antibiotics is a major health problem, particularly in diseases such as NTM-PD with long courses of treatment where resistance mechanisms can spontaneously manifest. The data presented at ID Week 2024 confirm the high potency of SPR719 against both macrolide susceptible and resistant MAC strains, with a low propensity for the spontaneous development of resistance mechanisms. Importantly, these characteristics were maintained in the combination with current standard of care (SOC) antibiotics used in the treatment of NTM-PD, and presented lower resistance compared to SOC antibiotics alone.”
Poster Presentation Highlights
- Activity of SPR719 and current standard of care antibiotics (clarithromycin, ethambutol and rifampin) were evaluated for potency (MIC concentration testing), propensity for the spontaneous development of drug-resistance (spontaneous mutation frequency [SMF] assay) and potential interactions for combination treatment (antibacterial synergy testing) against both macrolide susceptible and macrolide resistant mycobacterium avian complex (MAC) strains.
- SPR719 selection concentrations as low as 2-fold the MIC suppressed the emergence of resistance against both tested MAC isolates. Mutation frequencies for SPR719 against MAC observed in this study were about 3 orders of magnitude lower than those for SOC comparators tested in this study.
- In-line with previous reports, SPR719 demonstrated a high degree of potency with MIC values of 2 ug/mL for both macrolide susceptible and resistant strains. No resistant colonies were isolated when SPR719 was combined with clarithromycin or ethambutol in the SMF assay.
- In summary, SPR719 had a low propensity for resistance development in this study and showed no instances of antagonism when combined with clarithromycin or ethambutol, highlighting its potential for use in prolonged combination regimens typically required to treat NTM-PD.
About Nontuberculous Mycobacterium Pulmonary Disease (NTM-PD)
NTM-PD, also known as NTM lung disease, is caused by bacteria naturally found in soil, dust, and water. These bacteria are members of the Mycobacterium family and are distinct from tuberculosis and leprosy. The most common bacteria that cause of NTM infections is the Mycobacterium avium complex (MAC). NTM is a growing global health concern with significant unmet medical needs. Although rare, the incidence of NTM pulmonary disease is increasing worldwide. It is estimated that approximately 130,000 patients suffer from NTM in the U.S. and Europe, a figure that is growing at a rate of
About Spero Therapeutics
Spero Therapeutics, headquartered in Cambridge, Massachusetts, is a multi-asset clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and MDR bacterial infections with high unmet need. For more information, visit www.sperotherapeutics.com
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the timing, progress and results of Spero's preclinical studies, clinical trials and research and development programs; the potential benefits of any of Spero’s current or future product candidates in treating patients; and Spero’s strategy, goals and anticipated financial performance, milestones, business plans and focus. . In some cases, forward-looking statements may be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue," the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including whether tebipenem HBr, SPR720 and SPR206 will advance through the clinical trial process on a timely basis, or at all, taking into account the effects of possible regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, clinical trial design and clinical outcomes; whether the results of such trials will warrant submission for approval from the FDA or equivalent foreign regulatory agencies; whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval; whether the FDA will require any additional clinical data or place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be established; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; Spero's reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; Spero's need for additional funding; the ability to commercialize Spero's product candidates, if approved; Spero's ability to retain key personnel; Spero's leadership transitions; whether Spero's cash resources will be sufficient to fund its continuing operations for the periods and/or trials anticipated; and other factors discussed in the "Risk Factors" set forth in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Spero explicitly disclaims any obligation to update any forward-looking statements.
Investor Relations Contact:
Shai Biran, PhD
Spero Therapeutics
IR@Sperotherapeutics.com
Media Inquiries:
media@sperotherapeutics.com
FAQ
What is the significance of SPR719's low propensity for resistance development in NTM-PD treatment?
How does SPR719's mutation frequency compare to standard of care antibiotics for NTM-PD?
What are the potential benefits of SPR720 (SPRO) for NTM-PD treatment based on the IDWeek 2024 presentation?
How did SPR719 perform when combined with other antibiotics used in NTM-PD treatment?
