Aptevo Therapeutics Highlights Compelling Safety and Strong Remission Rates for Mipletamig in Frontline AML at ASH 2025

Rhea-AI Summary

Aptevo Therapeutics (NASDAQ:APVO) presented preliminary Phase 1b/2 RAINIER data for mipletamig (CD123 x CD3) combined with azacitidine and venetoclax for newly diagnosed AML patients unfit for intensive chemotherapy at ASH on December 8, 2025.

Key readouts: 100% of patients in Cohorts 1–3 remained free of cytokine release syndrome (CRS); 93% ORR among evaluable patients; 87% CR/CRi; 73% CR; 60% of MRD-evaluable CR/CRi patients were MRD negative; 43% of ORR patients had TP53 mutations. Median age was 75. The triplet was generally well tolerated; infusion-related reactions and hematologic events were the most common adverse events. The trial is continuing enrollment across additional dose levels.

Positive

• 100% of patients across cohorts remained free of CRS
• 93% ORR among evaluable patients
• 87% CR/CRi rate reported
• 60% MRD-negative among MRD-evaluable CR/CRi patients
• 43% ORR patients had TP53 mutations

Negative

• Infusion-related reactions were among the most common adverse events
• Hematologic events were among the most common adverse events
• Median patient age 75 reflects an older, higher-risk population

Key Figures

CRS-free patients 100% Cohorts 1–3 in RAINIER frontline AML trial

Overall response rate 93% Evaluable patients treated with mipletamig + AZA/VEN

CR/CRi rate 87% Evaluable frontline AML patients

Complete remission 73% Patients achieving CR in RAINIER Cohorts 1–3

MRD-negative in CR/CRi 60% MRD-evaluable CR/CRi patients

TP53-mutated in ORR 43% ORR patients with TP53 mutation

Median patient age 75 years Frontline AML population unfit for intensive chemotherapy

Market Reality Check

$1.24 Last Close

Volume Volume 534,459 is at 0.88x the 20-day average, showing no pre-news accumulation. normal

Technical Shares at $1.34 are trading well below the $10.75 200-day moving average, reflecting a depressed longer-term trend.

Peers on Argus 1 Up 1 Down

Peers show mixed moves: GRI -28.19%, XBIO -3.56% weaker, while QNRX +24.48%, OGEN +6.07%, ONCO +5.68% are stronger. Momentum scanner flags only GRI (up 8.15%) and OGEN (down 5.65%), reinforcing a stock-specific setup for APVO.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 10	Preclinical pipeline data	Positive	+6.1%	Debut of trispecific APVO451 with tumor‑localized T‑cell and APC activation.
Nov 06	Earnings and pipeline	Positive	+2.8%	Q3 report with high AML remission rates, no CRS, and added financing runway.
Oct 08	Conference participation	Positive	-2.8%	Announcement of multiple Q4 conference appearances and planned RAINIER data.
Sep 16	Clinical trial update	Positive	+4.2%	RAINIER Cohort 3 showed 100% remission and favorable safety in AML.
Sep 04	Pipeline expansion	Positive	-3.5%	Launch of two next‑generation trispecifics, expanding CD3 oncology pipeline.

Pattern Detected

Recent clinically focused and pipeline news has more often led to positive price reactions, but there are notable divergences on seemingly positive updates.

Recent Company History

Over the past few months, Aptevo has steadily highlighted its CD3‑based oncology pipeline. RAINIER trial updates for mipletamig in frontline AML, including a 100% remission cohort and no CRS, have previously coincided with gains of 4.17% and other positive moves. The company also expanded into trispecific antibodies, debuting APVO451 and APVO452, and reported Q3 results with additional capital raised and cash of $21.1M. Today’s ASH 2025 data further extend this clinical narrative around T‑cell engagement and safety.

Market Pulse Summary

The stock moved -7.5% in the session following this news. A negative reaction despite compelling remission and safety data would fit prior divergence episodes where positive conference and pipeline news coincided with declines of 2.84% and 3.55%. With shares already well below the $10.75 200-day moving average and 99.55% under the $298 52-week high, sentiment had been weak before this update. Past financing-related filings and equity structures could also have weighed on risk perceptions even as clinical evidence around mipletamig’s profile improved.

Key Terms

cytokine release syndrome medical

"100% of patients in Cohorts 1-3 remain free of cytokine release syndrome"

An intense immune overreaction in which the body's defense system releases a large surge of signaling proteins, causing fever, low blood pressure, breathing trouble or organ stress; imagine the immune system's alarm going into overdrive and flooding the body with emergency responders. Investors care because this side effect can slow or block regulatory approval, increase clinical trial costs and liabilities, limit how widely a therapy can be used, and therefore affect a drug's market value and sales potential.

overall response rate medical

"93% overall response rate (ORR) among evaluable patients"

Overall response rate is the percentage of patients in a clinical study whose measurable disease shrinks or disappears after receiving a treatment. Investors watch it like a product’s “hit rate” because higher response rates can signal a drug’s effectiveness, boost chances of regulatory approval and market demand, and affect a company’s future revenue prospects, similar to how a higher batting average suggests a more reliable player.

complete remission medical

"87% achieved CR/CRi* 73% achieved CR"

Complete remission means that medical tests and exams show no detectable signs or symptoms of a disease after treatment, though it does not guarantee the disease is permanently gone. Investors care because complete remission rates are a clear, measurable outcome used by regulators and doctors to judge a therapy’s effectiveness; like a fire appearing fully extinguished, it can boost a drug’s perceived value and commercial prospects while still requiring ongoing monitoring.

minimum residual disease medical

"60% of MRD evaluable CR/CRi patients achieved minimum residual disease negative status"

Minimum residual disease (MRD) is the small number of cancer cells that can remain in the body after treatment, often too few to cause symptoms but detectable with sensitive lab tests. For investors, MRD matters because it predicts the risk of relapse, influences how well a therapy or diagnostic performs in clinical trials, and can affect regulatory decisions and market value much like a smoke alarm indicating a hidden fire risk in a building.

tp53 medical

"43% of ORR patients had a TP53 genetic mutation"

tp53 is a gene that makes the p53 protein, which acts like a cellular quality-control inspector that halts damaged cells or triggers their self-destruction. It matters to investors because mutations in tp53 are common in many cancers and influence how patients respond to treatments, how diagnostic tests and targeted drugs are developed, and how clinical trials and regulatory decisions are designed—so changes in tp53-related science can affect the commercial prospects of oncology therapies and diagnostics.

phase 1b/2 medical

"ongoing Phase 1b/2 RAINIER study evaluating mipletamig"

Phase 1b/2 is a combined early-stage human study that first checks a drug’s safety and side effects in a small group and then expands to test whether it shows signs of working in patients. Think of it as a product test that first confirms it’s safe to use, then looks for early evidence of benefit; positive results can significantly reduce clinical risk and increase a company’s value, while negative results raise the opposite.

bispecific medical

"mipletamig, a CD123 x CD3 bispecific molecule, in combination with azacitidine"

A bispecific molecule is a therapeutic designed to bind two different biological targets at once — imagine a two-headed key that fits two locks simultaneously. For investors, bispecific therapies matter because that dual-action can make a treatment more effective or selective, potentially improving clinical results, altering safety profiles, and creating a stronger commercial edge; those factors directly affect development risk, regulatory chances, and future revenue prospects.

AI-generated analysis. Not financial advice.

100% of patients in Cohorts 1-3 remain free of cytokine release syndrome

CRIS-7-derived CD3 design underpins a controlled T-cell response, supporting the differentiated safety profile, combinability with standard of care

SEATTLE, WA / ACCESS Newswire / December 9, 2025 / Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies, presented preliminary results from its ongoing Phase 1b/2 RAINIER study evaluating mipletamig, a CD123 x CD3 bispecific molecule, in combination with azacitidine and venetoclax (AZA/VEN) for newly diagnosed acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. The data were presented on December 8, 2025, in a poster session at the American Society of Hematology (ASH) Annual Meeting.

Across dose-optimization Cohorts 1-3, mipletamig combined with AZA/VEN demonstrated high remission rates and a compelling safety/tolerability profile, reinforcing the potential of T-cell engagement in frontline AML when safety can be effectively managed. Aptevo's proprietary use of the CRIS-7-derived CD3 binding domain differentiates mipletamig in the category.

Key Findings

• 100% of treated patients remained free of cytokine release syndrome (CRS) across cohorts to date

• 93% overall response rate (ORR) among evaluable patients

• 87% achieved CR/CRi*

• 73% achieved CR

• 60% of MRD evaluable CR/CRi patients achieved minimum residual disease negative status, a result that is typically associated with stronger, more durable responses

• 43% of ORR patients had a TP53 genetic mutation, a marker that is typically associated with poor prognosis in AML patients

^*Remission = complete remission (CR) and, complete remission with blood markers that have not yet recovered (CRi).

Median patient age was 75, reflecting a population that is underserved by intensive therapies. In the RAINIER trial to date, the triplet regimen was generally well tolerated. Infusion-related reactions and hematologic events were the most common adverse events, consistent with expectations for this patient population. Importantly, no CRS was seen, supporting the molecule's differentiated safety profile in combination therapy.

"These data, particularly the remission rates and absence of CRS, underscore the promise of mipletamig as part of a frontline AML regimen," said Dirk Huebner, MD, Chief Medical Officer. "We are encouraged by the safety and efficacy profile we are seeing across cohorts, and we look forward to advancing the program into later-stage evaluation."

The RAINIER study continues to enroll patients across additional dose levels. Mipletamig's design leverages Aptevo's ADAPTIR™ platform to deliver targeted T-cell engagement with the goal of minimizing systemic immune activation-an important factor in realizing the full therapeutic potential of T-cell engagers in AML.

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, being evaluated for the treatment of AML, is differentiated by design to redirect the immune system of the patient to destroy leukemic cells and leukemic stem cells expressing the target antigen CD123, which is a compelling target for AML due to its overexpression on leukemic stem cells and AML blasts. This antibody-like recombinant protein therapeutic 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 CRS by use of the CRIS-7-derived CD3 binding pathway an approach that differentiates Aptevo from competitors. Mipletamig has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act. Orphan drug designation provides key advantages-including the opportunity to seek U.S. market exclusivity for a specific period of time upon approval, FDA fee reductions, and access to development and tax credits. Mipletamig has been evaluated in more than 100 patients over three trials to date.

About Aptevo Therapeutics
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 has two clinical candidates. 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 ("orphan status") for AML according to the Orphan Drug Act. ALG.APV-527, a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4, is being co-developed with Alligator Bioscience and was most recently evaluated in a Phase 1 clinical trial for the treatment of multiple solid tumor types likely to express 5T4. The Company has six preclinical candidates with different mechanisms of action designed to target a range of solid tumors. All pipeline candidates were created from two proprietary platforms, ADAPTIRand ADAPTIR-FLEX. 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, Aptevo's expectations about the activity, efficacy, safety, tolerability and durability of its therapeutic candidates and potential use of any such candidates, including in combination with other drugs, as therapeutics for treatment of disease, its expectations regarding the effectiveness of its ADAPTIR and ADAPTIR-FLEX platforms, statements related to the progress of Aptevo's clinical programs, including statements related to anticipated clinical and regulatory milestones, whether further study of mipletamig in a Phase 1b dose optimization trial focusing on multiple doses of mipletamig in combination with venetoclax + azacitidine on a targeted patient population will continue to show remissions, whether Aptevo's final trial results will vary from its earlier assessment, whether Aptevo's strategy will translate into an improved overall survival in AML, especially among patient subgroups with poor prognosis, whether further study of ALG.APV-527 across multiple tumor types will continue to show clinical benefit, the possibility and timing of interim data readouts for ALG.APV-527, statements related to Aptevo's ability to generate stockholder value, whether Aptevo will continue to have momentum in its business in the future, and any other statements containing the words "may," "continue to," "believes," "knows," "expects," "optimism," "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 should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo's expectations. Investors are, therefore, 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. For instance, actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the uncertainties inherent in the results of preliminary or interim data and preclinical studies being predictive of the results of later-stage clinical trials, initiation, enrollment and maintenance of patients, and the completion of clinical trials, the availability and timing of data from ongoing clinical trials, the trial design includes combination therapies that may make it difficult to accurately ascertain the benefits of mipletamig, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners or raise funds on acceptable terms or at all and other matters that could affect the availability or commercial potential of Aptevo's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises, geopolitical risks, including the current war between Russia and Ukraine and any other military event that could evolve out of any of the current conflicts, and macroeconomic conditions such as economic uncertainty, imposition of tariffs, rising inflation and interest rates, continued market volatility and decreased consumer confidence. These risks are not exhaustive, Aptevo faces known and unknown risks. Additional risks and factors that may affect results are set forth in Aptevo's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and its subsequent reports on Form 10-Q and current reports on Form 8-K. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Aptevo's expectations in any forward-looking statement. 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
Head, 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

FAQ

What were the mipletamig (APVO) remission rates reported at ASH 2025?

Aptevo reported a 93% ORR, 87% CR/CRi, and 73% CR among evaluable patients.

Did mipletamig (APVO) cause cytokine release syndrome in the RAINIER cohorts?

No CRS events were reported; 100% of patients in Cohorts 1–3 remained free of CRS.

What safety issues were observed with mipletamig plus AZA/VEN in the RAINIER study?

The most common adverse events were infusion-related reactions and hematologic events; the regimen was generally well tolerated.

How many mipletamig-treated CR/CRi patients were MRD negative at ASH 2025?

60% of MRD-evaluable CR/CRi patients achieved MRD-negative status.

What is the patient population and median age in the RAINIER mipletamig study?

Newly diagnosed AML patients unfit for intensive chemotherapy with a median age of 75 years.

Will Aptevo continue clinical development of mipletamig after ASH 2025 data?

Yes, the RAINIER study is continuing to enroll patients across additional dose levels.