Aptose Clinical Data Featured in Poster Presentation at the 2024 ASH Annual Meeting Support Tuspetinib Triple Drug Therapy for Newly Diagnosed AML
Aptose Biosciences presented clinical data for tuspetinib (TUS) at the 66th ASH Annual Meeting, highlighting its potential in treating acute myeloid leukemia (AML). The data supports the advancement of TUS+VEN+AZA triplet therapy for newly diagnosed AML patients.
Key findings show that TUS as a single agent achieved 60% and 42% CR/CRh rates with 80mg in FLT3 mutated and all-comer VEN-naïve AML respectively. In combination therapy, TUS+VEN showed 40% ORR with 80mg TUS + 400mg VEN in FLT3 mutated patients, with 83% of these patients having failed prior-VEN treatment.
The drug demonstrated favorable safety profiles both as monotherapy and in combination, with no dose-limiting toxicities through 160mg daily dosing, no drug-related discontinuations, and no deaths.
Aptose Biosciences ha presentato dati clinici per tuspetinib (TUS) al 66° Congresso Annuale dell'ASH, evidenziando il suo potenziale nel trattamento della leucemia mieloide acuta (LMA). I dati supportano l'avanzamento della terapia tripla TUS+VEN+AZA per pazienti con LMA di nuova diagnosi.
I principali risultati mostrano che TUS, come agente singolo, ha raggiunto tassi di CR/CRh del 60% e 42% con 80mg nei pazienti con mutazione FLT3 e negli AML naïve verso VEN rispettivamente. Nella terapia combinata, TUS+VEN ha mostrato un tasso di risposta oggettiva (ORR) del 40% con 80mg di TUS + 400mg di VEN nei pazienti con mutazione FLT3, con l'83% di questi pazienti che ha fallito il trattamento precedente con VEN.
Il farmaco ha dimostrato profili di sicurezza favorevoli sia come monoterapia che in combinazione, senza tossicità dose-limitanti attraverso dosaggi giornalieri fino a 160mg, senza interruzioni correlate al farmaco e senza decessi.
Aptose Biosciences presentó datos clínicos para tuspetinib (TUS) en la 66ª Reunión Anual de ASH, destacando su potencial en el tratamiento de la leucemia mieloide aguda (LMA). Los datos respaldan el avance de la terapia triple TUS+VEN+AZA para pacientes con LMA recién diagnosticada.
Los hallazgos clave muestran que TUS como agente único alcanzó tasas de CR/CRh del 60% y 42% con 80mg en AML mutado por FLT3 y en todos los AML naïve a VEN, respectivamente. En la terapia combinada, TUS+VEN mostró un ORR del 40% con 80mg de TUS + 400mg de VEN en pacientes mutados por FLT3, con el 83% de estos pacientes habiendo fallado en tratamientos anteriores con VEN.
El medicamento demostró perfiles de seguridad favorables tanto como monoterapia como en combinación, sin toxicidades limitantes por dosis a través de dosis diarias de 160mg, sin interrupciones relacionadas con el medicamento y sin muertes.
Aptose Biosciences는 제66회 ASH 연례 회의에서 tuspetinib (TUS)의 임상 데이터를 발표하며 급성 골수성 백혈병 (AML) 치료에서의 잠재력을 강조했습니다. 이 데이터는 새로 진단된 AML 환자를 위한 TUS+VEN+AZA 삼중 요법의 발전을 지원합니다.
주요 결과는 TUS가 단독 요법으로 80mg을 사용했을 때 FLT3 변이가 있는 환자에서 60%의 CR/CRh 비율과 모든 AML 환자에서 VEN-naïve로 42%의 비율을 달성했음을 보여줍니다. 병합 요법에서 TUS+VEN은 FLT3 변이가 있는 환자에서 80mg TUS + 400mg VEN 조합으로 40%의 객관적 반응률(ORR)을 보였으며, 이들 중 83%는 이전의 VEN 치료에서 실패한 환자였습니다.
이 약물은 단일 요법과 조합 요법 모두에서 유리한 안전성 프로필을 보여주었으며, 160mg의 최대 일일 복용량까지 용량 한계 독성이 없었고, 약물과 관련된 중단 사례도 없었으며, 사망자도 없었습니다.
Aptose Biosciences a présenté des données cliniques sur le tuspetinib (TUS) lors de la 66e Réunion Annuelle de l'ASH, mettant en avant son potentiel dans le traitement de la leucémie myéloïde aiguë (LMA). Les données soutiennent l'avancement de la thérapie triple TUS+VEN+AZA pour les patients récemment diagnostiqués avec une LMA.
Les résultats clés montrent que TUS, en tant qu'agent unique, a atteint des taux de CR/CRh de 60 % et 42 % avec 80 mg chez les patients mutés FLT3 et tous les AML naïfs de VEN respectivement. Dans la thérapie combinée, TUS+VEN a montré un taux de réponse objective (ORR) de 40 % avec 80 mg de TUS + 400 mg de VEN chez les patients mutés FLT3, dont 83 % avaient échoué lors de traitements précédents avec VEN.
Le médicament a montré des profils de sécurité favorables tant en monothérapie qu'en combinaison, sans toxicités limitantes par dose avec des doses journalières allant jusqu'à 160 mg, sans interruptions liées au médicament et sans décès.
Aptose Biosciences präsentierte klinische Daten zu tuspetinib (TUS) auf dem 66. ASH-Jahrestreffen und hob das Potenzial zur Behandlung der akuten myeloischen Leukämie (AML) hervor. Die Daten unterstützen den Fortschritt der TUS+VEN+AZA Dreifachtherapie für frisch diagnostizierte AML-Patienten.
Wesentliche Erkenntnisse zeigen, dass TUS als Einzeltherapie mit 80mg bei FLT3-mutanter AML eine CR/CRh-Rate von 60% und bei VEN-naiven Patienten eine Rate von 42% erreichte. In der Kombinationstherapie zeigte TUS+VEN eine 40%ige ORR mit 80mg TUS + 400mg VEN bei FLT3-mutanter AML, wobei 83% dieser Patienten zuvor mit VEN behandelt worden waren.
Das Medikament zeigte sowohl in der Monotherapie als auch in der Kombination günstige Sicherheitsprofile, ohne dosislimitierende Toxizitäten bei einer täglichen Dosis von bis zu 160mg, ohne medikamentenbedingte Abbrüche und ohne Todesfälle.
- Strong efficacy with 60% CR/CRh rate in FLT3 mutated AML patients at 80mg dose
- 40% Overall Response Rate in combination therapy for FLT3 mutated patients
- Favorable safety profile with no dose-limiting toxicities up to 160mg
- Effective in patients who failed prior treatments (83% response in prior-VEN failure patients)
- Demonstrated activity across broad AML populations including difficult-to-treat cases
- Lower response rate (42%) in all-comer VEN-naïve AML compared to FLT3 mutated patients
- sample size in combination therapy (n=79 patients)
Insights
The clinical data presented at ASH demonstrates significant progress for Aptose's tuspetinib (TUS) in treating Acute Myeloid Leukemia (AML). The results are particularly noteworthy with 60% CR/CRh response rates in FLT3 mutated patients and 40% ORR in combination therapy. The drug's ability to target venetoclax resistance mechanisms while maintaining a favorable safety profile positions it uniquely in the AML treatment landscape.
The triplet therapy approach (TUS+VEN+AZA) shows promise in addressing a major unmet need in newly diagnosed AML patients who can't receive intensive chemotherapy. The 33% CRc rate and broad efficacy across genetic subgroups, including difficult-to-treat mutations like TP53 and RAS, suggests potential for improved treatment outcomes. The absence of dose-limiting toxicities through 160mg daily dosing and clean safety profile significantly de-risks the clinical development pathway.
The breadth of tuspetinib's activity across multiple AML populations is clinically significant. Most notably, its effectiveness in FLT3 wildtype patients, representing ~70% of AML cases, addresses a substantial market opportunity. The drug's ability to achieve responses in patients who failed prior venetoclax treatment is particularly valuable, as resistance to venetoclax remains a significant clinical challenge.
The favorable safety profile, with no differentiation syndrome, QTc issues, or drug-related discontinuations, suggests potential for broad clinical adoption. The oral once-daily dosing enhances patient compliance compared to more intensive regimens. The combination data with venetoclax showing activity in heavily pretreated patients who failed both prior-VEN and FLT3i treatments indicates potential for tuspetinib to become a key component of AML treatment strategies.
- TUS+VEN+AZA Triplet Frontline Therapy in Newly Diagnosed AML Patients Now Enrolling at U.S. Sites
- TUS and TUS+VEN Broadly Active Across AML Populations, with Favorable Safety
- TUS-based therapies are active in FLT3 wildtype, representing ~
70% of AML patients - TUS Targets VEN Resistance Mechanisms, Enabling TUS+VEN to Achieve Responses in Difficult-to-treat Prior-VEN Failure AML
SAN DIEGO and TORONTO, Dec. 09, 2024 (GLOBE NEWSWIRE) -- Aptose Biosciences Inc. (“Aptose” or the “Company”) (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, today featured a wealth of clinical data for Aptose’s lead compound tuspetinib (TUS) in a poster presentation at the 66th American Society of Hematology (ASH) Annual Meeting in San Diego.
Poster title: “Phase 1 Safety and Efficacy of Tuspetinib Plus Venetoclax Combination Therapy in Study Participants with Relapsed or Refractory Acute Myeloid Leukemia (AML) Support Exploration of Triplet Combination Therapy of Tuspetinib Plus Venetoclax and Azacitidine for Newly Diagnosed AML”
Key Findings and Messages:
- TUS+VEN+AZA triplet trial is proceeding in newly diagnosed AML patients
- TUS+VEN retains activity in the difficult-to-treat prior-VEN AML population
- TUS+VEN is active in FLT3 wildtype, representing ~
70% of AML patients - TUS+VEN is well tolerated and can be safely co-administered
- TUS+VEN is active across broad populations of R/R AML
- Combination of TUS with VEN may avoid VEN resistance
- TUS+VEN+AZA triplet may establish a more effective, mutation agnostic standard of care for chemotherapy ineligible AML patients
Tuspetinib (TUS), being developed by Aptose and originally created by Hanmi Pharmaceutical Co., is being advanced as the TUS+VEN+AZA triplet (tuspetinib+venetoclax+azacitidine) for frontline therapy of newly diagnosed AML patients ineligible for intensive chemotherapy. TUS is a once daily, oral, multi-kinase inhibitor selectively targeting kinases that drive AML cell proliferation. In the Phase 1/2 APTIVATE trial of relapsed/refractory (R/R) AML patients (NCT03850574), TUS single agent and the TUS+VEN doublet demonstrated excellent safety and broad efficacy across AML genetic subgroups – including those with adverse mutations in TP53 and RAS genes, and those with mutated or unmutated (wildtype) FLT3 genes.
“Our extensive dataset with TUS and TUS+VEN support advancement of the TUS+VEN+AZA triplet frontline therapy and we are pleased to now have the TUSCANY triplet clinical trial up and running,” said Rafael Bejar, MD, PhD, Chief Medical Officer at Aptose. “TUS targets known VEN resistance mechanisms, and in combination with VEN, could prevent emergence of resistance to both agents. Moreover, with its breadth of activity and unique safety profile, TUS, as part of a triplet therapy regimen, may target AML’s greatest unmet needs and largest markets.”
Highlights of the ASH poster presentation:
TUS as Single Agent (n= 93 Patients)
60% and42% CR/CRh with 80 mg TUS in FLT3 mutated and all-comer VEN-naïve AML33% CRc &42% ORR (CR, CRp, CRh, CRi or PR) in FLT3 mutated and VEN-naïve patients- Includes 40, 80, 120, and 160 mg TUS dose as a single agent
- Includes those who failed prior therapy with venetoclax
- Includes those with mutated or unmutated FLT3, those who failed prior-HSCT, priorFLT3i, prior-chemotherapy, prior-HMA
- TUS once daily orally as a single agent achieved CR/CRh responses at four different dose levels (40, 80, 120, and 160 mg) with no dose limiting toxicities (no DLTs)
- TUS showed a favorable safety profile with no DLTs through 160 mg per day, and no drug related discontinuations, no QTc, no differentiation syndrome, and no deaths
TUS/VEN Combination Therapy (n= 79 Patients)
40% ORR with 80 mg TUS + 400 mg VEN in FLT3 mutated patients. Among these83% (5/6) had failed prior-VEN treatment and50% (3/6) had failed both prior-VEN and FLT3i treatment.- TUS+VEN achieved responses among diverse R/R AML with adverse mutations in VEN-naïve, prior-VEN, FLT3WT, FLT3MUT, prior-FLT3
- TUS+VEN showed favorable safety and tolerability with no new or unexpected safety signals, no drug related CPK elevations, no differentiation syndrome, and no deaths
The ASH poster presentation is available on Aptose’s website here.
About Aptose
Aptose Biosciences is a clinical-stage biotechnology company committed to developing precision medicines addressing unmet medical needs in oncology, with an initial focus on hematology. The Company’s lead clinical-stage compound tuspetinib (TUS) is an oral kinase inhibitor that has demonstrated activity as a monotherapy and in combination therapy in patients with relapsed or refractory acute myeloid leukemia (AML) and is being developed as a frontline triplet therapy in newly diagnosed AML. For more information, please visit www.aptose.com.
Forward Looking Statements
This press release may contain forward-looking statements within the meaning of Canadian and U.S. securities laws, including, but not limited to, statements relating to the therapeutic potential of tuspetinib, its clinical development and safety profile and potential for accelerated approval, the value creating milestones planned for tuspetinib as part of a triplet study, including that TUS+VEN+AZA may establish a broader and safer standard of care and may target AML’s greatest unmet needs and largest markets, as well as statements relating to the Company’s plans, objectives, expectations and intentions and other statements including words such as “continue”, “expect”, “intend”, “will”, “should”, “would”, “may”, and other similar expressions. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by us are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance or achievements described in this press release. Such factors could include, among others: our ability to obtain the capital required for research and operations and to continue as a going concern; the inherent risks in early stage drug development including demonstrating efficacy; development time/cost and the regulatory approval process; the progress of our clinical trials; our ability to find and enter into agreements with potential partners; our ability to attract and retain key personnel; changing market conditions; inability of new manufacturers to produce acceptable batches of GMP in sufficient quantities; unexpected manufacturing defects; and other risks detailed from time-to-time in our ongoing quarterly filings, annual information forms, annual reports and annual filings with Canadian securities regulators and the United States Securities and Exchange Commission.
Should one or more of these risks or uncertainties materialize, or should the assumptions set out in the section entitled "Risk Factors" in our filings with Canadian securities regulators and the United States Securities and Exchange Commission underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this press release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by law. We cannot assure you that such statements will prove to be accurate as actual results and future events could differ materially from those anticipated in such statements. Investors are cautioned that forward-looking statements are not guarantees of future performance and accordingly investors are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty therein.
For further information, please contact:
Aptose Biosciences Inc.
Susan Pietropaolo
Corporate Communications & Investor Relations
201-923-2049
spietropaolo@aptose.com
FAQ
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