Aptevo Reports 93% Clinical Benefit Rate with Mipletamig Triplet in Difficult-to-Treat TP53-Mutated Frontline AML
Early RAINIER data for mipletamig in TP53‑mutated frontline AML show high remission and clinical benefit rates versus historical venetoclax plus azacitidine outcomes.
Rhea-AI Summary
Aptevo Therapeutics (APVO) reported a 93% clinical benefit rate for its mipletamig triplet regimen in evaluable frontline TP53‑mutated acute myeloid leukemia (AML) patients. Of 14 patients treated with mipletamig plus venetoclax and azacitidine, 13 derived clinical benefit and 11 (79%) achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi).
The 79% CR/CRi rate compares with a published 41% composite remission rate for venetoclax plus azacitidine alone in treatment‑naïve TP53‑mutated AML with poor‑risk cytogenetics. The ongoing RAINIER Phase 1b/2 trial is in dose optimization and is expected to complete this phase by year‑end, with regulatory interaction planned in 1H27. Mipletamig, Aptevo’s lead wholly owned bispecific candidate, has orphan drug designation for AML and is designed to target CD123‑expressing leukemic cells while aiming to limit cytokine release syndrome.
Positive
- 93% clinical benefit rate (13 of 14 evaluable TP53‑mutated AML patients) with mipletamig plus venetoclax and azacitidine.
- 79% CR/CRi rate (11 of 14 patients), including nine complete remissions, in this difficult‑to‑treat AML population.
- Remission rate benchmark of 79% CR/CRi compares favorably with a published 41% composite remission rate for venetoclax plus azacitidine alone.
- RAINIER dose‑optimization phase is ongoing with completion expected by year‑end, moving the program toward Phase 2 and regulatory discussions.
- Mipletamig orphan drug designation for AML provides potential regulatory and market exclusivity advantages if successfully developed.
Negative
- Small patient sample of 14 evaluable TP53‑mutated AML patients limits generalizability of current efficacy signals.
- Early‑stage development: RAINIER is still in Phase 1b dose optimization, with key regulatory interaction not planned until 1H27, implying a long path to potential approval.
Market reaction after Phase 1b/2 clinical data: APVO -15.00%
Following this news, APVO has declined 15.00%, reflecting a significant negative market reaction. Argus tracked a trough of -15.0% from its starting point during tracking. Our momentum scanner has triggered 21 alerts so far, indicating elevated trading interest and price volatility. The stock is currently trading at $2.21. Trading volume is exceptionally heavy at 372.1x the average, suggesting significant selling pressure.
Data tracked by StockTitan Argus (15 min delayed). Upgrade to Gold for real-time data.
Key Figures
Historical Context
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| Aug 14 | earnings report | Neutral | -13.5% | Business update highlighted clinical progress, funding, collaboration, cash, and quarterly financing activity. |
| Aug 13 | private financing | Negative | -13.5% | Warrant exercise and PIPE generated proceeds while adding warrants and potential resale shares. |
| Aug 12 | private financing | Negative | -15.4% | Warrant inducement and PIPE financing added potential shares and warrants for working capital. |
| Jul 27 | patent filing | Positive | -4.1% | Patent application covered a Nectin-4 and PD-L1 dual-targeting backbone for solid tumors. |
| Jun 30 | research grant | Positive | -2.4% | Non-dilutive grant funded APVO451 IND-enabling work and candidate selection activities. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
APVO's recent news events were more often followed by negative 24-hour reactions, including after positive clinical, patent, and grant updates.
Key Terms
morphologic leukemia-free state medical
cytokine release syndrome medical
orphan drug designation regulatory
ind-enabling studies regulatory
AI-generated analysis. How Rhea-AI works. Not financial advice.
Remission results nearly double published ven/aza outcomes in patients with historically limited treatment success
SEATTLE, WA / ACCESS Newswire / September 3, 2026 / Aptevo Therapeutics Inc. (Nasdaq:APVO), a clinical-stage biotechnology company developing novel multispecific immuno-oncology therapeutics, today announced a
"TP53-mutated AML remains one of the most challenging AML subpopulations to treat," said Dirk Huebner, M.D., Chief Medical Officer of Aptevo. "Seeing this level of clinical benefit with the mipletamig triplet in a patient population that historically has not responded well to treatment is exciting. These results support mipletamig as a promising frontline treatment for one of the most difficult-to-treat forms of AML."
Of 14 evaluable TP53-mutated patients treated with mipletamig in combination with venetoclax and azacitidine, including two patients from the previously completed dose expansion trial, 13 (
*Clinical benefit includes complete remission (CR), complete remission with incomplete hematologic recovery (CRi), partial response (PR) and morphologic leukemia-free state (MLFS).
These results are encouraging because patients with TP53-mutated AML have historically had limited treatment success. The
**Benchmark comparison based on Pollyea DA, et al. Clinical Cancer Research. 2022;28(24):5272-5279. Comparison is to treatment-naïve patients with poor-risk cytogenetics and TP53-mutated AML treated with venetoclax plus azacitidine.
TP53-mutated AML is one of the most difficult forms of acute myeloid leukemia to treat, with patients historically experiencing lower remission rates and poorer outcomes than those with other forms of AML. Because TP53 mutations can make leukemia cells more resistant to treatment, achieving deep and durable responses in this patient population has been particularly challenging. As a result, the robust responses observed with mipletamig in TP53-mutated AML are especially encouraging and highlight its potential to address a significant unmet medical need.
Currently, the RAINIER study is evaluating mipletamig in combination with venetoclax and azacitidine in frontline AML patients who are unfit to receive standard high-intensity chemotherapy in a dose optimization trial. This phase of the trial is expected to be completed by year-end, and regulatory interaction is planned for 1H27 to determine next steps.
About the RAINIER Trial
RAINIER, a frontline AML study, is a Phase 1b/2 dose optimization, multi-center, multi-cohort, open-label study. Subjects are adults aged 18 or older, newly diagnosed with AML who are not eligible for intensive induction chemotherapy. RAINIER will be conducted in two parts. First, a Phase 1b dose optimization study in frontline AML patients followed by a Phase 2 study. The Phase 1b trial consists of 28-day cycles of treatment across multiple, sequential cohorts.
About Mipletamig
Aptevo's wholly owned lead proprietary drug candidate, mipletamig, is being evaluated for the treatment of AML. Mipletamig is designed to redirect the patient's immune system to destroy leukemic cells and leukemic stem cells expressing CD123, which is overexpressed on leukemic stem cells and AML blasts. Mipletamig is designed to engage both leukemic cells and T cells of the immune system and bring them closely together to trigger the destruction of leukemic cells. Mipletamig is purposefully designed to reduce the likelihood and severity of cytokine release syndrome by using the CRIS-7-derived CD3 binding pathway, an approach that differentiates Aptevo from competitors.
About Aptevo
Aptevo Therapeutics Inc. (Nasdaq: APVO) is a clinical-stage biotechnology company focused on developing novel bispecific and trispecific immunotherapies for the treatment of cancer. The Company's lead clinical candidate, mipletamig, is currently being evaluated in RAINIER, a two-part Phase 1b/2 trial for the treatment of frontline acute myeloid leukemia in combination with standard-of-care venetoclax + azacitidine. Mipletamig has received orphan drug designation for AML under the Orphan Drug Act.
In the solid tumor space, Aptevo's lead assets are focused on well-established targets to progress novel immunomodulatory platform backbones that are conditionally active only in the tumor.
This work includes advancing APVO451, a targeted trispecific immunotherapy candidate for solid tumors, and a strategic collaboration with Niowave to develop up to three radiopharmaceutical oncology programs. The first radiopharmaceutical program is expected to target nectin-4, a tumor-associated antigen expressed in multiple solid tumor types. Both preclinical molecules are expected to advance into investigational new drug (IND)-enabling studies in 2027.
The Company's eight pipeline candidates are created using its proprietary ADAPTIR™ and ADAPTIR-FLEX™ platforms, which are designed to generate differentiated multispecific therapeutics. The Aptevo mission is to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com.
Safe Harbor Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, without limitation, statements regarding Aptevo's expectations about the activity, efficacy, safety, tolerability and durability of mipletamig, including in combination with venetoclax and azacitidine; statements related to the progress of the RAINIER trial, including statements related to anticipated clinical and regulatory milestones; statements related to the responses observed in patients with TP53-mutated AML and whether further study of mipletamig in combination with venetoclax + azacitidine will continue to show clinical benefit in patients with TP53-mutated AML; whether Aptevo's strategy will translate into an improved overall survival rate in acute myeloid leukemia (AML); whether the mipletamig data in combination therapy will be indicative of later stage clinical trials; whether Aptevo's strategy will translate into improved overall survival in AML, especially among patient subgroups with poor prognosis; its expectations regarding the effectiveness of its ADAPTIR and ADAPTIR-FLEX platform; development and continued development of Aptevo's current and potential future molecules, including Aptevo's trispecific candidates and their future development and efficacy with respect to addressing multiple solid tumor types; whether pre-clinical studies of Aptevo's trispecific candidates will show the desired anti-tumor efficacy, mechanism of action and safety profile and whether Aptevo's trispecific candidates will function with new mechanisms of action compared to our previous candidates and synergistically induce a biological response; the potential benefits, timing, scope and outcomes of the co-development collaboration with Niowave; and any statements containing the words "may," "continue to," "believes," "expects," "potential," "designed," "promising," "plans," "will" and similar expressions are intended to identify forward-looking statements.
These forward-looking statements are based on Aptevo's current intentions, beliefs and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors are cautioned not to place undue reliance on any forward-looking statement. There are several important factors that could cause Aptevo's actual results to differ materially from those indicated by such forward-looking statements, including a deterioration in Aptevo's business or prospects; further assessment of preliminary or interim data or different results from later clinical trials; adverse events and unanticipated problems; adverse developments in clinical development, including unexpected safety issues observed during a clinical trial; and changes in regulatory, social, macroeconomic and political conditions. Additional risks and factors that may affect results are set forth in Aptevo's filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2026, and its subsequent reports on Form 10-Q and current reports on Form 8-K. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not assume any obligation to update any forward-looking statement to reflect new information, events or circumstances.
CONTACT:
Miriam Weber Miller
Vice President, Investor Relations & Corporate Communications
Aptevo Therapeutics
Email: IR@apvo.com or Millerm@apvo.com
Phone: 206-859-6628
SOURCE: Aptevo Therapeutics
View the original press release on ACCESS Newswire