Molecular Partners (NASDAQ: MOLN) presented updated Phase 1/2a data for its tetra‑specific T‑cell engager MP0533 in relapsed/refractory acute myeloid leukemia (AML) at the American Society of Hematology (ASH) meeting on December 7, 2025. By the September 1, 2025 data cut‑off, 54 patients had received MP0533 and 8 of 48 evaluable patients responded, including five composite complete responses and three morphologic leukemia‑free states. Densified, higher‑frequency dosing (cohorts 8–9) was well tolerated, produced markedly higher serum exposure in cycle 1, and showed early signs of antitumor activity, especially in patients with low baseline disease burden.
Positive
- 54 patients treated as of September 2025
- 8 of 48 evaluable patients achieved a clinical response
- Five composite complete responses (3 CR, 2 CR with partial hematologic recovery)
- Densified dosing markedly improved serum exposure in the first treatment cycle
- Responses clustered in patients with low baseline disease burden
Negative
- Responder rate limited to 8 of 48 evaluable patients
- Responses were largely confined to low‑blast patients, raising questions about broader applicability
- Data derive from early‑phase, small cohorts; cohort 10 remains ongoing with confirmatory data expected in 2026
Key Figures
Patients treated 54 Phase 1/2a MP0533 AML/MDS trial as of Sept 1 2025
Evaluable patients 48 Efficacy set for MP0533 trial
Responders 8 Patients achieving a response
Composite complete responses 5 3 CR and 2 CR with partial hematologic recovery
Morphologic leukemia‑free states 3 Patients reaching MLFS
Low‑blast responders 6 of 8 Responders with baseline bone marrow blasts < 20 %
Blast‑reduction subgroup 11 of 14 Patients achieving > 50 % blast reduction
Long remission duration > 1 year One cohort 8 patient remains in complete remission
Market Reality Check
$4.52 Last Close
Volume Volume 1,271 is well below the 20‑day average of 6,036, indicating limited pre‑news trading interest.
Technical Shares trade above the 200‑day moving average of $4.01 but remain below the 52‑week high of $6.24.
Peers on Argus
Peers displayed mixed moves: INO up 2.48 %, while NKTX, ACTU, AVTX and GNLX fell between 1.07 % and 2.17 %, suggesting the MOLN reaction is driven by company‑specific data rather than sector momentum.
Historical Context
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Nov 12 | Radiotherapy data (MP0712) | Positive | +2.5 % | New human imaging and mechanism data for DLL3‑targeting MP0712 |
| Nov 03 | Preclinical proof‑of‑concept for logic‑gated CD3 Switch‑DARPin | Positive | +12.4 % | Data supporting a novel multispecific engager platform |
| Oct 30 | Q3 2025 earnings and pipeline update | Neutral | ‑3.6 % | Financial results and updates on MP0712, MP0533, MP0317 |
| Aug 25 | H1 2025 earnings | Neutral | ‑7.7 % | Financial numbers, pipeline progress, workforce reduction |
Positive R&D milestones tend to trigger short‑term price gains, while mixed financial releases generate muted or negative moves. The MP0533 data fits this trend, offering a catalyst for potential upside if Phase 2 data confirm efficacy.
Over the past six months, Molecular Partners has highlighted pipeline progress across its DARPin platform. November’s DLL3‑targeting radiotherapy data and Switch‑DARPin preclinical proof drove double‑digit gains. Earlier MP0533 AML preview generated both enthusiasm and caution, reflecting the early‑stage nature of the program. Earnings releases in August and October combined financial results with clinical milestones, resulting in modest price declines, underscoring the market’s emphasis on data‑driven catalysts.
Market Pulse Summary
The updated Phase 1/2a data for MP0533 highlight 54 treated patients, 8 responders, and a durable remission lasting over a year in a cohort‑8 participant. The evidence suggests the greatest benefit occurs in patients with low bone‑marrow blast burden, while the densified dosing schedule appears safe and achieves higher exposure. Investors will be watching cohort 10 results due in 2026, as well as potential Phase 2 designs that could position MP0533 for earlier‑line use or combination strategies with standard AML backbones. Strategic partnership discussions are already underway, which could accelerate development and broaden commercial prospects.
Key Terms
Phase 1/2a
medical
The combined Phase 1/2a trial merges early safety assessment with preliminary efficacy readouts, enabling rapid dose‑finding while gathering signals of activity. For investors, this design shortens the timeline to pivotal data and reduces the overall development risk.
relapsed/refractory
medical
Patients whose disease has returned after therapy (relapsed) or who do not respond to standard treatment (refractory). This population represents an unmet medical need, often justifying accelerated regulatory pathways and premium pricing.
T‑cell engager
medical
A bispecific or multispecific molecule that bridges T‑cells to tumor cells, triggering immune‑mediated killing. MP0533 is a tetra‑specific DARPin‑based engager, a novel architecture that may offer improved selectivity and reduced off‑target toxicity compared with traditional antibody‑based formats.
AI‑generated analysis. Not financial advice.
- Poster outlines clinical benefit with an acceptable safety profile across nine dosing regimens.
- Accelerated step‑up dosing and higher frequency proved feasible and increased drug exposure.
- Six of eight responders had low bone‑marrow blast counts at baseline, reinforcing the hypothesis that patients with lower disease burden derive the greatest benefit.
ZURICH‑SCHLIEREN, Switzerland and CONCORD, Mass., Dec. 7 2025 – Molecular Partners AG (NASDAQ: MOLN), a clinical‑stage biotech focused on DARPin therapeutics, will present updated Phase 1/2a data for the tetra‑specific T‑cell engager MP0533 in relapsed/refractory AML at the 67th ASH Annual Meeting in Orlando, Florida (December 6‑9, 2025).
The multicenter, open‑label study (NCT05673057) evaluated MP0533 in patients with AML or MDS/AML who have failed prior therapy. Cohorts 8 and 9, which employed densified dosing, demonstrated tolerability, markedly higher serum concentrations in cycle 1, and early signs of antitumor activity.
“The higher‑frequency regimen appears very encouraging, especially in patients with low disease burden,” said Prof. Courtney DiNardo, MD, Division of Cancer Medicine, MD Anderson Cancer Center, co‑chair of the MP0533 dose‑escalation review committee.
Key data as of September 1 2025:
- 54 patients treated with MP0533
- 8 of 48 evaluable patients responded
- 5 composite complete responses (3 CR, 2 CR with partial hematologic recovery)
- 3 patients reached a morphologic leukemia‑free state
- 6 of the 8 responders, and 11 of 14 patients with >50 % blast reduction, had baseline marrow blasts <20 %
- One cohort‑8 patient remains in complete remission for >1 year
MP0533 is a tetra‑specific DARPin that simultaneously targets CD33, CD123, CD70 on AML cells and CD3 on T‑cells. By increasing avidity with the number of antigens present, the molecule preferentially binds leukemic cells while sparing healthy tissue, potentially widening the therapeutic window.
Poster details:
- Title: “Phase 1/2 study of MP0533, a tetra‑specific T‑cell engager (CD33 × CD123 × CD70 × CD3), in patients with relapsed/refractory AML or MDS/AML: Initial results from optimized treatment regimen including densified MP0533 dosing and adapted premedication.”
- Session: 616 – Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies (Poster II)
- Date: December 7 2025, 6:00–8:00 PM ET, OCCC West Halls B3‑B4
- Publication number: 3419
Technical Insight:
- The DARPin scaffold offers a modular platform that can be engineered to bind up to five targets, delivering high affinity in a compact, stable protein format.
- Compared with conventional antibody‑based bispecifics, DARPins are smaller (≈14–18 kDa per domain), enabling higher tissue penetration and potentially lower manufacturing costs.
- MP0533’s multi‑antigen approach addresses AML heterogeneity; AML blasts often co‑express CD33, CD123, and CD70, whereas normal hematopoietic cells typically express only one or none, reducing off‑target cytotoxicity.
Market Implications:
- AML remains a high‑unmet‑need market with roughly 20,000 new cases in the U.S. annually and a 5‑year survival rate under 30 % for relapsed/refractory disease.
- Current standard‑of‑care options (e.g., venetoclax + azacitidine) provide modest benefits; a novel T‑cell engager could capture a premium niche, especially if it demonstrates activity in low‑blast patients.
- Investors should monitor upcoming cohort 10 data (2026) and any early‑phase combination studies with hypomethylating agents or FLT3 inhibitors, which could broaden the addressable population.
- Strategic partnerships are already being explored; a collaborative development model could accelerate regulatory timelines and expand commercial reach.
Looking ahead, the key questions for MOLN will be:
- Can the favorable safety and exposure profile of densified dosing translate into consistent, deeper responses in larger cohorts?
- Will MP0533 demonstrate sufficient efficacy to move into a pivotal Phase 2/3 trial, possibly in earlier‑line AML or in combination with existing therapies?
- How will the market price the potential of a DARPin‑based T‑cell engager relative to competing platforms such as BiTEs and CAR‑T therapies?
FAQ
What Phase 1/2a results did Molecular Partners announce for MP0533 at ASH 2025?
Updated data showed 54 patients treated, with 8 of 48 evaluable responders and improved exposure using densified dosing.
How many complete responses were observed in the MP0533 AML trial?
Five composite complete responses were reported: three complete remissions and two CRs with partial hematologic recovery.
Which dosing regimens yielded better exposure and tolerability?
Cohorts 8 and 9, which employed densified, higher‑frequency dosing, were tolerable and produced markedly improved serum exposure in cycle 1.
Which patient subgroup benefited most from MP0533?
Six of eight responders and most patients achieving >50 % blast reduction had baseline marrow blasts <20 %, indicating a benefit in lower disease‑burden patients.
How long have any patients remained on MP0533, and when is further data expected?
One cohort 8 patient has stayed in complete remission for over a year; cohort 10 is ongoing with additional data anticipated in 2026.
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