On December 8, 2025 BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, reported its position as the leader in chronic lymphocytic leukemia (CLL) innovation by showcasing the depth, quality, and momentum of its hematology portfolio at the 67th ASH (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida. The totality of BeOne’s ASH (Free ASH Whitepaper) data reinforce BRUKINSA (zanubrutinib) as the foundational Bruton’s tyrosine kinase inhibitor (BTKi) of choice.

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"At ASH (Free ASH Whitepaper) 2025, we will present new data from across our CLL franchise, highlighting both the strength of BRUKINSA and the potential of BGB-16673," said Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne. "Long-term data are the gold standard in CLL, and BRUKINSA continues to deliver the high levels of durable progression-free and overall survival that patients and physicians should demand from a BTK inhibitor. BGB-16673, the most advanced BTK degrader in the clinic with over 800 patients dosed to date, potentially represents the next wave of foundational innovation in oncology."

BRUKINSA continues to demonstrate unprecedented long-term efficacy with a favorable safety profile over more than six years of follow-up in treatment-naïve CLL/SLL.

In SEQUOIA (NCT03336333), a randomized, multicenter, global Phase 3 trial, BRUKINSA maintained progression-free survival (PFS) superiority versus bendamustine plus rituximab (BR) with an estimated 74% PFS at six years in treatment-naïve CLL or small lymphocytic lymphoma (SLL) compared with 32% PFS for BR. Highlights include:

Arms A, B and C: BRUKINSA vs BR, as well as BRUKINSA in patients with del(17p) (Poster Presentation: 2129)
COVID-19 adjusted PFS rates were 77% (95% CI, 70.1-81.8) for BRUKINSA and 33% (95% CI, 25.5-40.4) for BR.
The overall survival (OS) at 72 months was 84% for BRUKINSA and 80% with BR. After adjusting for COVID-19, the OS rates were 88% and 82%, respectively.
In patients with del(17p), the six-year PFS was 64% (65% after COVID-19 adjustment) and the 72-month OS was 83%.
The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.
"SEQUOIA’s longer follow-up strengthens the evidence for continuous zanubrutinib use," said Constantine Tam, M.B.B.S., M.D., Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University. "Patients continued to show durable disease control and consistent safety across study arms, meaningfully raising the bar for CLL patients, including those with harder-to-treat CLL."

Arm D: BRUKINSA plus venetoclax in patients with or without del(17p) and/or TP53 mutations (Poster Presentation: 5669)
In the overall patient population, in which 58% of patients had del(17p) and/or TP53 mutation, the median PFS was not reached; the 36-month PFS rate was 87%.
The 36-month PFS rate for patients with del(17p) and/or TP53 mutation was 87% and for patients without del(17p) and TP53 mutation was 89%.
A total of 42 patients completed the BRUKINSA plus venetoclax combination and continued BRUKINSA monotherapy.
At 12 months following the combination period, peripheral blood undetectable minimal residual disease (uMRD) was maintained in 100% (18/18) of patients without del(17p) and TP53.
At 18 months following the combination period, uMRD was maintained in 92% (22/24) of patients with del(17p) and/or TP53 mutation.
The safety profile of BRUKINSA plus venetoclax was generally tolerable and no unexpected safety signals were identified.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) now recommend zanubrutinib plus venetoclax as a preferred first-line regimen for CLL/SLL.
New patient-reported outcomes data in R/R CLL suggest BRUKINSA may offer a more manageable side effect profile. Up to six-years of follow-up data support BRUKINSA’s foundational role in CLL/SLL as the only BTK inhibitor with enduring PFS and long-term benefit over another BTK inhibitor.

ALPINE (NCT03734016) is a global, randomized, open-label, multicenter, Phase 3 study of BRUKINSA versus ibrutinib in patients with R/R CLL/SLL who received ≥1 prior systemic therapy. Highlights include:

Symptom-based progression-free survival as a clinically relevant and patient-centric endpoint (Oral Presentation: 711)
This study is among the first analyses of patients with CLL/SLL to demonstrate a statistically and clinically meaningful association between longitudinal symptom deterioration and disease progression using joint modeling.
Deterioration in patient-reported fatigue, insomnia, and nausea/vomiting emerged as strong symptomatic indicators of disease progression.
Compared with ibrutinib, patients on BRUKINSA showed reduced risk of symptom deterioration associated with earlier disease progression.
The analysis showed that patients on BRUKINSA had lower odds of symptom worsening for nausea/vomiting, fatigue, pain, and insomnia.
Up to six years of follow-up of patients from the BRUKINSA arm of ALPINE who continued in a long-term extension study (LTE-1; Poster Presentation: 2123)
With up to 73.5 months of follow-up, the median PFS for all patients was a striking 52.5 months; the 60-month PFS rate was 47.3% (50.4% adjusted for COVID-19). These results redefine what is expected for this patient population.
Among patients with del(17p), the median PFS was 49.9 months; the 60-month PFS rate was 38.2% (40.5% adjusted for COVID-19).
With longer follow-up, the prevalence of most adverse events of special interest remained stable year-over-year.
BGB-16673 (BTK degrader) clinical data demonstrates rapid, robust and deepening responses in patients with heavily pretreated R/R CLL/SLL, including those with prior BTKi treatment and mutations that confer resistance to BTK inhibitors. (Oral Presentation: 85)

Updated results from CaDAnCe-101 (NCT05006716), an ongoing open-label, Phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies, showed responses across R/R CLL/SLL patient types, including those who had previously been treated with BTK inhibitors, BCL2 inhibitors, noncovalent BTK inhibitors, and those with BTK inhibitor resistance mutations. Highlights include:

With a median follow-up of 19.8 months, 54.4% of patients remain on treatment. Across all doses, ORR was 85.3% and CR/CR with incomplete count recovery (CRi) rate was 2.9% with responses deepening over time.
In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%.
In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%.
The 12- and 18-month PFS rates were 73.5% and 65.9% respectively.
BGB-16673 was generally well tolerated in this heavily pretreated population with no treatment-related deaths and no new toxicities identified with a median treatment duration of 13.6 months.
For more information about our presence at the 2025 ASH (Free ASH Whitepaper) Annual Meeting and Exposition, please visit our meeting hub: congress.beonemedicines.com.

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.2,3

About BGB-16673

BGB-16673 is a potential first-in-class Bruton’s tyrosine kinase (BTK) protein degrader and is the most advanced protein degrader in the clinic, with nearly 800 patients dosed to date in an extensive global clinical development program. This program includes three randomized Phase 3 trials in R/R CLL, including the head-to-head Phase 3 trial versus pirtobrutinib, which began enrolling in Q4 2025. Originating from BeOne’s chimeric degradation activation compound (CDAC) platform, BGB-16673 is designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease.

The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and adult patients with R/R mantle cell lymphoma (MCL). Additionally, the European Medicines Agency (EMA) granted BGB-16673 PRIority MEdicines (PRIME) designation for the treatment of patients with Waldenstrom’s macroglobulinemia (WM) previously treated with a BTK inhibitor.

About BRUKINSA (zanubrutinib)

BRUKINSA is an orally available, small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing. BRUKINSA is also the only BTK inhibitor to demonstrate superiority to another BTK inhibitor in a Phase 3 study.

The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 75 markets, and more than 247,000 patients have been treated globally.

Select Important Safety Information

Serious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity (including drug-induced liver injury).

In the pooled safety population (N=1729), the most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Please see full U.S. Prescribing Information including U.S. Patient Information.

The information provided in this press release is intended for a global audience. Product indications vary by region.

(Press release, BeOne Medicines, DEC 8, 2025, View Source [SID1234661276])

On December 8, 2025 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported the presentation of final data from its Phase 1/1b trial of soquelitinib in patients with T cell lymphoma in an oral session at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is taking place December 6-9, 2025 in Orlando, FL. The presentation highlights preclinical and clinical data supporting the development of soquelitinib in oncology and immune and inflammatory diseases, including data detailing its mechanism of action.

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"The T-cell lymphomas are devastating diseases, associated with dismal outcomes, and are thus an area of high unmet need," said Ryan Wilcox, M.D., Ph.D., Associate Professor of Internal Medicine, University of Michigan Medical School. "In the relapsed/refractory setting, complete and durable responses are rarely achieved with currently available agents. The Phase 1 data demonstrate impressive progression free and overall survival in relapsed/refractory patients treated with soquelitinib. Several patients experienced complete and durable responses, some of which were maintained on therapy more than two years. For most relapsed/refractory PTCL patients, an overall survival less than 6 months is anticipated. In the phase 1 study, median progression free survival was 6.2 months and median overall survival exceeded 2 years. These results provide the foundation for the ongoing registration Phase 3 trial in relapsed/refractory peripheral T cell lymphoma."

The trial enrolled 75 patients (27 in dose escalation portion and 48 in dose expansion portion) with various T cell lymphomas, including peripheral T cell lymphoma (PTCL), T follicular helper cell lymphoma (TFHC), natural killer cell T cell lymphoma (NKTCL), cutaneous T cell lymphoma (CTCL), anaplastic large cell lymphoma (ALCL) and adult T cell lymphoma/leukemia (ATLL). The median number of prior therapies was 3 (range 1-18), with only 31% achieving an objective response to their most recent prior therapy. In the dose escalation portion, patients received a twice-daily dose of soquelitinib of 100 mg, 200 mg, 400 mg or 600 mg, and the 200 mg twice-daily dose was selected for the dose expansion portion based on biomarker studies indicating that doses of 200mg or higher achieved complete occupancy of the ITK target with the drug.

Key highlights from the data supporting the ongoing registration Phase 3 trial in relapsed/refractory PTCL include:

No dose limiting toxicities or significant adverse events were observed in any patients in all dose cohorts up to 600 mg twice-daily, including no myelosuppression or immunosuppression
Objective and durable tumor responses were seen in the 200 mg twice-daily cohort (N=36) with 6 patients experiencing complete responses
In the 200 mg twice-daily cohort, it was determined that patients with between ≥1 and ≤3 prior therapies and an adequate peripheral blood lymphocyte count (N=24) were most likely to be responders to therapy. In this patient population:
Objective responses were seen in 9 of 24 patients including 6 complete responses and 3 partial responses
Median progression free survival (PFS) was 6.2 months, including an 18-month PFS of 30%
Median overall survival (OS) was 28.1 months, including a 24-month OS of 67%

Key highlights from the data supporting soquelitinib’s mechanism of action (Th1 skewing and blocking Th2 and Th17 differentiation) and use in immune and inflammatory diseases include:

In vitro studies demonstrated that at appropriate doses, soquelitinib produces Th1 skewing, which is an immunologic property resulting from the blockade of Th2 differentiation and a shift to Th1
Biomarker studies evaluating blood samples and tumor biopsies showed an increase in Th1 in blood and tumor samples and a reduction in serum IL-5, consistent with inhibiting Th2 and Th17 cells
For 6 patients, paired tumor biopsies were compared at baseline and day 8 and showed an increase in intratumor Th1 cells with treatment analyzed using RNA sequencing

"The data presented at ASH (Free ASH Whitepaper) provides foundational information for the future development of soquelitinib and our ITK platform across oncology, immune disease and inflammation," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "In oncology, the data show that soquelitinib could be a new treatment option for T cell lymphomas, including in patients with advanced, aggressive disease. The data not only support our ongoing registration Phase 3 trial in PTCL, but also show immunobiological effects that demonstrate soquelitinib’s mechanism of action of affecting T cell differentiation via ITK inhibition. The mechanism operates upstream in T cell signaling pathways, which may indicate that resistance pathways are unlikely to evolve."

Dr. Miller added, "Outside of oncology, we are focused on the development of soquelitinib in atopic dermatitis and evaluating its potential in a broad range of immune and inflammatory diseases. We plan to present additional data from extension cohort 4 of our Phase 1 atopic dermatitis trial in January and initiate a Phase 2 trial in this indication in early Q1 2026."

Corvus is currently enrolling patients in a registration Phase 3 clinical trial of soquelitinib in patients with relapsed/refractory PTCL at multiple clinical sites. This randomized controlled trial is anticipated to enroll a total of 150 patients with relapsed/refractory PTCL and is evaluating soquelitinib versus physicians’ choice of either belinostat or pralatrexate. The primary endpoint of the trial is progression free survival. There are no FDA fully approved agents for the treatment of relapsed/refractory PTCL, and the FDA has granted soquelitinib Orphan Drug Designation for the treatment of T cell lymphoma and Fast Track designation for treatment of adult patients with relapsed or refractory PTCL after at least 2 lines of systemic therapy. The Company anticipates reporting interim data from the Phase 3 trial in late 2026 and completing the trial in 2027.

The ASH (Free ASH Whitepaper) oral presentation slides are available on the Publications and Presentations page of the Corvus website.

(Press release, Corvus Pharmaceuticals, DEC 8, 2025, View Source [SID1234661275])

On December 8, 2025 Terns Pharmaceuticals, Inc. (Terns or the Company) (Nasdaq: TERN), a clinical-stage oncology company, reported that updated and expanded data from the ongoing CARDINAL trial of TERN-701, a novel investigational allosteric BCR::ABL1 inhibitor, in patients with previously treated chronic myeloid leukemia (CML) are being presented today at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place December 6-9, 2025 in Orlando, FL. The company will host a conference call and webcast for investors at 4:30pm ET today following the ASH (Free ASH Whitepaper) presentation.

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The ASH (Free ASH Whitepaper) presentation will be made available on the Terns Pharmaceuticals website simultaneously with the oral presentation by Elias Jabbour, MD, Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and lead investigator on the TERN-701 Phase 1 CARDINAL study. Presentation details are summarized below.

"We are delighted that our investigators can share these unprecedented Phase 1 data for TERN-701 with patient groups and the broader hematology community at ASH (Free ASH Whitepaper). The 64% major molecular response (MMR) achievement rate reported in the abstract is maintained in the expanded dataset presented at ASH (Free ASH Whitepaper). The safety profile and higher MMR achievement rate of 75% over 24 weeks at doses of 320mg and above supports selection of 320mg and 500mg QD as the recommended phase 2 doses (RP2Ds) for expansion. Study enrollment has accelerated and surpassed 85 patients which supports rapidly advancing TERN-701 through dose expansion cohorts, dose selection, and the initiation of pivotal studies," said Amy Burroughs, chief executive officer of Terns.

"We are particularly encouraged to see unprecedented rates of MMR in a highly refractory population, including compelling response achievement in patients with lack of efficacy on prior asciminib, ponatinib, and/or other marketed and investigational TKIs. In the RP2D dose range, we see a 36% DMR achievement rate by 24 weeks, highlighting the fast response kinetics of TERN-701. Importantly, with a median treatment duration of six months, we continue to see a favorable safety and tolerability profile at all doses, further positioning TERN-701 as the potential best-in-disease therapy in 2L+ and 1L CML, where we intend to focus pivotal clinical development," stated Emil Kuriakose, MD, chief medical officer of Terns.

"While therapies for CML have come a long way since imatinib, there remains an unmet need for new drugs that achieve early, broad and deep responses with a safety/tolerability profile that allows long-term maintenance of response with improved quality of life for patients. Based on the data to date, TERN-701 represents an innovative treatment option that has the potential to achieve this important goal. I am excited to help advance this therapy for the benefit of CML patients," said Dr. Jabbour.

The ASH (Free ASH Whitepaper) oral presentation today reports data from the ongoing dose escalation and dose expansion parts of the CARDINAL study of TERN-701 in patients with previously treated CML. As of the September 13, 2025 cutoff date, 63 patients were enrolled.

Assessment of all dose cohorts (160mg – 500mg, n=63)

•
Of 38 efficacy-evaluable patients:

•
Overall (cumulative) MMR rate of 74% (28/38) by 24 weeks, with 64% (18/28) achieving MMR and 100% (10/10) maintaining MMR

•
MMR overall and achieved by 24 weeks in difficult to treat patient subgroups:

•
Lack of efficacy to last tyrosine kinase inhibitor (TKI): 65% (13/20) overall; 63% (12/19) achieved

•
Lack of tolerability to prior TKI: 88% (14/16) overall; 71% (5/7) achieved

•
Prior asciminib: 60% (6/10) overall; 43% (3/7) achieved

•
Prior asciminib, ponatinib and/or investigational TKI: 67% (8/12) overall; 50% (4/8) achieved

•
Deep molecular response (DMR) achievement rate by 24 weeks of 29% (10/34)

•
No patients had lost MMR at the time of data cutoff

•
Enrolled patients had heavily pretreated, refractory disease:

•
Median of 3 prior TKIs; 60% had ≥3 prior TKIs

•
57% and 44% had baseline BCR::ABL1 >1% and >10%, respectively

•
64% discontinued their last TKI due to lack of efficacy

•
38% had prior asciminib treatment (75% had lack of efficacy and 25% had lack of tolerability)

•
22% had prior ponatinib treatment (79% had lack of efficacy and 21% had lack of tolerability)

•
15% with BCR::ABL1 mutations (10% with T315I and 5% with non-T315I mutations)

•
Encouraging safety profile:

•
87% (55/63) of patients remained on treatment as of the data cutoff; with discontinuations due to disease progression (n=4), adverse events (n=1), and physician / patient decision or lost to follow up (n=3)

•
No dose-limiting toxicities (DLTs) were observed in dose escalation, and a maximum tolerated dose (MTD) was not reached

•
The majority of treatment-emergent adverse events (TEAEs) were low grade with no apparent dose relationship

•
Rates of cytopenia were generally low with less than 10% Grade 3 thrombocytopenia and neutropenia

•
Most common non-hematologic TEAEs were diarrhea (21%), headache (19%) and nausea (19%), all Grade 1 or 2

•
Grade 3 or higher TEAEs were all less than 10%, most commonly neutropenia (8%) and thrombocytopenia (8%)

•
TERN-701 exposures were approximately dose proportional across the dose range

•
Encouraging MMR achievement rates in patients with lack of efficacy to prior asciminib:

Subgroup Baseline Characteristics MMR achieved by 24 weeks 
Prior asciminib (n=10) No MMR at baseline 7/10 (70%)   3/7 (43%)
Prior lack of efficacy 6/7 (86%) 2/6 (33%)
Prior intolerance only 1/7 (14%) 1/1 (100%)
Assessment of patient cohorts at doses ≥ 320mg QD (n=53)

•
Similar overall baseline characteristics to the full study population:

•
Median of 3 prior TKIs

•
56% and 47% had baseline BCR::ABL1 >1% and >10%, respectively

•
38% had prior asciminib treatment, 21% had prior ponatinib treatment

•
68% discontinued their last TKI due to efficacy

•
In 30 efficacy evaluable patients, overall MMR rate of 80% (24/30) by 24 weeks, with 75% (18/24) achieving MMR and 100% maintaining MMR (6/6)

•
DMR achievement rate by 24 weeks of 36% (10/28)

•
Molecular responses observed across full spectrum of baseline BCR::ABL1 transcripts

Baseline BCR::ABL1 (Patients at doses ≥ 320 mg QD)

MR5

(n=0)

MR4.5

(n=1)

MR4

(n=1)

MR3

(n=4)

MR2

(n=11)

MR1

(n=4)

>10%

(n=9)

LOGO

MR5 (DMR) 1 1 1 1 1 1
MR4.5 (DMR) 3
MR4 (DMR) 1 1 1
MR3 (MMR) 2 6 4
MR2 1
MR1 1 1
BCR::ABL >10% 3
Note: Table includes response evaluable non-T315Im patients that have ≥1 baseline assessment with at least six months of treatment at visit cutoff, achievement of MMR or better prior to six months or treatment discontinuation prior to six months for any reason (n=30). Diagonal, bolded cells represent stable disease. Up/right of diagonal, bolded cells represents improvement in molecular response (MR) category, while down/left represents loss of efficacy. MR represents a decrease in the number of cells in the blood with the BCR::ABL1 gene and is quantified as a percentage. MR5: ≤0.001%, MR4.5: >0.001 to 0.0032%, MR4: >0.0032 to 0.01%, MR3: >0.01 to 0.1%, MR2: >0.1 to 1%, MR1: >1 to 10%.

Details for the ASH (Free ASH Whitepaper) oral presentation are as follows:

Title: CARDINAL: A Phase 1 study of TERN-701, a novel investigational allosteric BCR::ABL1 inhibitor for patients with previously treated CML

Presenter: Elias Jabbour, MD, Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

Session Name: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Therapeutic agents to enhance patient outcomes

Session Date: December 8, 2025 at 2:45pm ET

Company Conference Call and Webcast Information

Terns will host a conference call and webcast for investors at 4:30pm ET on December 8, 2025 following the oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting. Members of the Terns management team will discuss additional TERN-701 data from CARDINAL, including patient vignettes, benchmarking comparisons and next steps for the development of TERN-701. The conference call will conclude with a Q&A session.

The webcast can be accessed in the investor relations section of the Company’s website. A replay of the event will be archived and available for a limited time.

About TERN-701 and CARDINAL Clinical Trial

TERN-701 is currently being evaluated in the CARDINAL trial (NCT06163430), a global multi-center dose escalation and dose-expansion clinical trial to assess safety, tolerability and efficacy in patients with previously treated chronic phase CML. The dose escalation portion of the CARDINAL trial completed in January 2025 with no DLTs observed up to the maximum dose of 500mg QD. Terns initiated the dose expansion portion of the trial in April 2025 with patients randomized to one of two dose cohorts (320mg or 500mg QD) with up to 40 patients per arm.

(Press release, Terns Pharmaceuticals, DEC 8, 2025, View Source [SID1234661274])

On December 8, 2025 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, reported key Revuforj (revumenib) presentations spanning the acute leukemia treatment continuum that have been presented at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in Orlando, Florida, December 6-9, 2025. In total, Syndax and its collaborators will present 12 Revuforj abstracts at the 2025 ASH (Free ASH Whitepaper) Annual Meeting. Revuforj is the Company’s oral, first-in-class, FDA-approved menin inhibitor.

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"We are thrilled to share new data, including the first real-world evidence for the class, showing that revumenib is highly efficacious with a favorable safety profile in multiple acute leukemia subtypes and settings, including in combination with standard of care therapies. Notably, the datasets show deep responses in R/R and frontline NPM1m and KMT2Ar acute leukemia, as well as encouraging safety and early efficacy in post-HSCT maintenance," said Nick Botwood, MBBS, Head of Research & Development and Chief Medical Officer at Syndax. "With the initiation earlier this year of the pivotal frontline trial in patients unfit for intensive chemotherapy, and the recent initiation of our pivotal frontline trial in fit patients, Syndax is well positioned to further expand the clinical data supporting revumenib and lead in the frontline setting with this exciting new class of therapy."

Overview of Key Revumenib Data Presented at the 67th ASH (Free ASH Whitepaper) Annual Meeting

Early real-world experience with revumenib outside of a clinical trial setting: A single center retrospective review of efficacy and tolerability (Abstract #3448)

This presentation reported efficacy and tolerability data from a single-center retrospective review of 17 patients treated with Revuforj outside of a clinical trial. The median age was 54 years (range: 23-79). 47% (8/17) of patients had KMT2Ar, 29% (5/17) had NPM1m, and 18% (3/17) had NUP98r acute leukemia. Patients had a median of four prior lines of therapy (range: 0-6), including 71% (12/17) with prior venetoclax and 35% (6/17) with prior hematopoietic stem cell transplant (HSCT).

Revuforj was used as part of combination therapy in 82% (14/17) of patients, with venetoclax and a hypomethylating agent being the most common partner. Of the 17 patients treated with Revuforj, 13 patients were included in the efficacy analysis (four patients were excluded: one with false positive KMT2Ar test result, one who received Revuforj only as post-HSCT maintenance, and two who received Revuforj as a treatment for measurable residual disease (MRD) positive disease). The overall response rate (ORR) was 77% (10/13), the composite complete remission (CRc) rate was 62% (8/13), and the CR/CRh rate was 31% (4/13). 75% (9/12) of patients were MRD negative at best response. Four patients proceeded to receive a HSCT after revumenib therapy. Among patients who received a HSCT, 75% (3/4) received revumenib as post-HSCT maintenance.

The early real-world evidence supports the safety and tolerability of Revuforj in clinical practice. The rate of Grade 3 or 4 non-hematological adverse events was 24% (4/17). There was no differentiation syndrome (DS) or QTc prolongation above Grade 3. DS and QTc did not lead to treatment discontinuation in any patient. The rate of revumenib dose reductions and discontinuations was low at 6% (1/17) and 6% (1/17), respectively.

"Among a real-world group of heavily pre-treated NPM1m, KMT2Ar, and NUP98r patients who received Revuforj as a monotherapy or in combination, it is very encouraging to observe the vast majority of patients achieve MRD negative responses and to see a meaningful number of patients proceed to a stem cell transplant with durable ongoing remissions. Along with excellent clinical activity, we observed that Revuforj was well-tolerated, including in combination with other therapies," said David Sallman, M.D., Associate Member in the Department of Malignant Hematology at Moffitt Cancer Center. "Our results underscore the potential for Revuforj to transform the standard of care for patients with menin-dependent acute leukemias."

Retrospective review of revumenib as post-HSCT maintenance in children with HOX-driven AML (Abstract #3461)

This study retrospectively analyzed ten pediatric patients with HOX-driven AML who received revumenib maintenance after HSCT at a single-center. The median age was 10 years (range: 1-18). 80% (8/10) had KMT2Ar and 20% (2/10) had NUP98r AML. 50% (5/10) of patients had ≥2 prior HSCTs.

Patients completed a median of 2 cycles (range: 1-4) of revumenib pre-HSCT. Patients began revumenib following HSCT, with planned continuation for up to 12 months. Patients resumed revumenib a median of 111 days (range: 58-175) post-HSCT. Patients completed a median of 11 revumenib cycles (range: 3-25) post-HSCT. At a median follow-up of 19 months (range: 4-41), all ten patients were alive, with one relapse, yielding a 90% relapse-free survival.

Revumenib was well tolerated in the post-HSCT maintenance setting, with most adverse events being low grade and manageable. No patients discontinued therapy due to drug-related toxicity.

Results from Phase 2 SAVE trial of revumenib with venetoclax and decitabine/cedazuridine in patients with newly diagnosed AML (Abstract #47)

The Phase 2 SAVE trial is an investigator-sponsored trial evaluating the all-oral combination of revumenib with venetoclax and decitabine/cedazuridine in pediatric and adult patients with R/R or newly diagnosed AML or MPAL harboring either NPM1m, KMT2Ar, or NUP98r alterations. Patients ≥12 years of age with these molecular subtypes who were not candidates for high-intensive chemotherapy were eligible to enroll in the newly diagnosed cohort.

At data cutoff (November 10, 2025), 21 newly diagnosed patients had been enrolled. The median age was 70 years (range: 60-83). 67% (14/21) had NPM1m and 33% (7/21) had KMT2Ar AML.

High rates of response, MRD negativity, and HSCT were observed among NPM1m and KMT2Ar AML patients who received the all-oral combination. The ORR was 86% (18/21) and the complete remission (CR) rate was 76% (16/21). The MRD negativity rate by flow cytometry was 100% (18/18) among responders. 33% (7/21) of patients proceeded to HSCT after receiving the combination, with 57% (4/7) having resumed revumenib as post-HSCT maintenance at the data cutoff.

With a median follow-up of 9 months, the median overall survival (OS) and event-free survival (EFS) were not reached.

The combination was generally well tolerated. The most common (>20%) Grade ≥3 treatment-emergent adverse events (TEAEs) were febrile neutropenia (48%), thrombocytopenia (33%), and neutropenia (24%). There was no treatment-emergent QTc prolongation above Grade 2. Two (10%) patients had Grade 3 treatment-emergent differentiation syndrome (DS) which promptly resolved with steroids. There was no treatment-emergent DS above Grade 3.

Results from Phase 1 trial of revumenib with intensive chemotherapy in patients with newly diagnosed KMT2Ar or NPM1m AML (SNDX-5613-0708) (Abstract #3425)

Preliminary data were reported from the Phase 1, multi-center, open-label, dose-escalation and dose-expansion trial of revumenib in combination with intensive chemotherapy (SNDX-5613-0708). Adults with newly diagnosed KMT2Ar, NPM1m, or NUP98r AML who were candidates for intensive chemotherapy were eligible to enroll. The primary endpoints were the occurrence of dose-limiting toxicities (DLTs) and safety. The secondary endpoints were PK parameters. Exploratory endpoints included the rate of CR, CRc, ORR, and MRD negative CR.

At the data cutoff (September 30, 2025), 30 patients had been enrolled and treated across two revumenib dose levels (DL1: revumenib 110 or 220 mg q12hr with/without strong CYP3A4i; DL2: 160 or 270 mg q12hr with/without strong CYP3A4i). The median age was 49 years (range: 19-71). 63% (19/30) had KMT2Ar and 37% (11/30) had NPM1m.

The safety profile of the combination was consistent with the profile for intensive chemotherapy alone. The most common treatment-related adverse events (TRAEs) of any Grade were decreases in neutrophil count (31%), anemia (23%), nausea (23%), and vomiting (23%) in DL1, and anemia (18%) in DL2. No cases of DS were reported. No events of QTc prolongation above Grade 3 were reported. The rates of TEAEs leading to revumenib reductions or discontinuations were low at 7% and 13%, respectively. One DLT of Grade 3 QTc prolongation was reported in DL1 in a patient taking several concomitant medications that can also prolong the QTc interval. This patient discontinued revumenib during Cycle 1; of note, at the end of Cycle 1, the patient had achieved MRD-negative CR and proceeded to HSCT.

The early data show encouraging clinical activity with the combination. Across both dose levels combined, the ORR was 96% (25/26), CRc rate was 92% (24/26), CR rate was 69% (18/26), and MRD negative CR rate was 86% (12/14) among patients with MRD results available. Data will continue to mature, and responses could deepen further with longer follow-up, particularly in DL2.

Time to count recovery was rapid and similar at both dose levels. The median time to neutrophil (≥1,000 cells/μL) recovery among CRc responders was 29 days in both DL1 and DL2 in Cycle 1. The median time to platelet (≥100,000 cells/μL) recovery among CRc responders was 28 days and 29 days in DL1 and DL2, respectively, in Cycle 1.

Syndax Investor Event

The Company will host an investor event on Monday, December 8, 2025, at 7:00 a.m. ET to discuss key Revuforj and Niktimvo data presented at the 67th ASH (Free ASH Whitepaper) Annual Meeting. The live audio webcast and accompanying slides for the event may be accessed through the Events & Presentations page of the Company’s website or directly through the meeting link here.

For those unable to join the live webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com for a limited time.

About Revuforj (revumenib)

Revuforj (revumenib) is an oral, first-in-class menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation as determined by an FDA-authorized test in adult and pediatric patients one year and older. Revuforj is also indicated for the treatment of R/R acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation in adult and pediatric patients one year and older who have no satisfactory alternative treatment options.

Multiple trials of revumenib are ongoing or planned across the treatment landscape, including in combination with standard of care therapies in newly diagnosed patients with NPM1m or KMT2Ar AML.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME, QTc PROLONGATION, and TORSADES DE POINTES

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

QTc prolongation and Torsades de Pointes have occurred in patients receiving Revuforj. Correct hypokalemia and hypomagnesemia prior to and during treatment. Do not initiate Revuforj in patients with QTcF > 450 msec. If QTc interval prolongation occurs, interrupt, reduce, or permanently discontinue Revuforj.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, rash, and/or hypotension.

In clinical trials, DS occurred in 60 (25%) of 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia. Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype acute leukemia (MPAL), and 9% of patients with acute lymphoblastic leukemia (ALL); DS occurred in 18% of patients with NPM1m AML. DS was Grade 3 or 4 in 12% of patients and fatal in 2 patients. The median time to initial onset was 9 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%.

Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours in adults or dexamethasone 0.25 mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids.

QTc Interval Prolongation and Torsades de Pointes: Revuforj can cause QT (QTc) interval prolongation and Torsades de Pointes.

Of the 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia in clinical trials, QTc interval prolongation was reported as an adverse reaction in 86 (36%) patients. QTc interval prolongation was Grade 3 in 15% and Grade 4 in 2%. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 10%, and the increase from baseline QTcF was greater than 60 msec in 24%. Revuforj dose reduction was required for 7% due to QTc interval prolongation. QTc prolongation occurred in 21% of the 34 patients less than 17 years old, 35% of the 146 patients 17 years to less than 65 years old, and 46% of the 61 patients 65 years or older. One patient had a fatal outcome of cardiac arrest, and one patient had non-sustained Torsades de Pointes.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to and throughout treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.

Interrupt Revuforj if QTcF increases >480 msec and <500 msec, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
Interrupt Revuforj if QTcF increases >500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns to ≤480 msec
Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia
Embryo-Fetal Toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj.

ADVERSE REACTIONS

Fatal adverse reactions occurred in 9 (4%) patients who received Revuforj, including 4 with sudden death, 2 with differentiation syndrome, 2 with hemorrhage, and 1 with cardiac arrest.

Serious adverse reactions were reported in 184 (76%) patients. The most frequent serious adverse reactions (≥10%) were infection (29%), febrile neutropenia (20%), bacterial infection (15%), differentiation syndrome (13%), and hemorrhage (11%).

The most common adverse reactions (≥20%) including laboratory abnormalities, were phosphate increased (51%), hemorrhage (48%), nausea (48%), infection without identified pathogen (46%), aspartate aminotransferase increased (44%), alanine aminotransferase increased (40%), creatinine increased (38%), musculoskeletal pain (37%), febrile neutropenia (37%), electrocardiogram QT prolonged (36%), potassium decreased (34%), parathyroid hormone intact increased (34%), alkaline phosphatase increased (33%), diarrhea (29%), bacterial infection (27%), triglycerides increased (27%), phosphate decreased (25%), differentiation syndrome (25%), fatigue (24%), edema (24%), viral infection (23%), decreased appetite (20%), and constipation (20%).

DRUG INTERACTIONS

Drug interactions can occur when Revuforj is concomitantly used with:

Strong CYP3A4 inhibitors: reduce Revuforj dose
Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj
QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec
SPECIFIC POPULATIONS

Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose.

Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.

Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.

Pediatric: monitor bone growth and development in pediatric patients.

Geriatric: no overall differences were observed in the effectiveness of Revuforj between patients who were 65 years and older, and younger patients. Compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.

To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see Full Prescribing Information, including BOXED WARNINGS.

(Press release, Syndax, DEC 8, 2025, View Source [SID1234661273])

On December 8, 2025 Recursion (Nasdaq: RXRX), a clinical-stage TechBio company decoding biology to radically improve lives, reported positive Phase 1b/2 data from the ongoing TUPELO trial of REC-4881, an investigational allosteric MEK1/2 inhibitor for familial adenomatous polyposis (FAP).

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Through an unbiased phenotypic screen of thousands of compounds, the earliest version of the Recursion OS identified selective MEK1/2 inhibition as a highly specific mechanism capable of reversing APC loss-of-function signatures. Using high-content cellular phenomics driven by AI, REC-4881 emerged as one of the strongest phenotypic rescue hits, reverting APC-deficient cells toward a healthy state and suppressing ERK/MAPK hyperactivation downstream of APC loss. Guided by this AI-driven insight, Recursion in-licensed REC-4881 from Takeda and redirected REC-4881—originally evaluated clinically in solid tumors—as a mechanistically aligned therapeutic candidate for FAP. REC-4881 is now the first MEK1/2 inhibitor ever studied clinically for this disease.

"The durable polyp-burden reduction demonstrated by REC-4881—especially the sustained effect seen at Week 25, 12 weeks after completing therapy—is highly encouraging for the FAP community," said Jessica Stout, D.O., Assistant Clinical Professor, University of Utah School of Medicine, and Principal Investigator of the TUPELO study. "Given the near-100% lifetime risk of colorectal cancer and the absence of any approved medical therapies, patients today often face a lifetime of intensive surveillance and life-altering surgeries. These Phase 2 results provide a meaningful basis for hope and support the potential for REC-4881 to offer a much-needed non-surgical option for this debilitating, life-long disease."

"These Phase 2 results mark a meaningful validation of the Recursion OS," said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. "An unbiased phenotypic insight from our platform and driven by AI—linking MEK1/2 inhibition to APC loss-of-function biology—has now translated into rapid, substantial, and durable reductions in polyp burden in patients. This is a powerful example of how even the earliest versions of the Recursion OS can uncover therapeutic opportunities in diseases with no approved pharmacotherapy options. And since this discovery, we’ve only added to the breadth, depth, and power of the Recursion OS; we believe this is the first of many potential medicines that will advance as our flywheel of discovery accelerates".
In the Phase 2 portion of the study, REC-4881 demonstrated rapid and durable reductions in polyp burden, with 43% median reduction in evaluable patients after 12 weeks of treatment. 75% of evaluable patients had a reduction in polyp burden in this same period. Importantly, the effect persisted well beyond the dosing period: 82% of evaluable patients (9 of 11) maintained reductions at Week 25—12 weeks after stopping therapy—with a 53% median decrease from baseline. These results are especially meaningful when considered alongside real-world natural history analyses showing that untreated FAP patients are expected to experience increases when left untreated .
"This program reflects a full validation cycle of the Recursion OS: an unbiased phenotypic signal identifying MEK1/2 inhibition as a rescue mechanism for APC loss-of-function, followed by mechanistic confirmation, clinical translation, and now encouraging human data in a disease with no approved medical therapies," said Najat Khan, Ph.D., Chief R&D and Commercial Officer and incoming President and CEO. "REC-4881, an allosteric MEK1/2 inhibitor, represents a first precision-medicine approach for the causal biology of FAP. In TUPELO, we are seeing rapid, substantial, and durable reductions in polyp burden — including sustained benefit after patients stop therapy. Equally important, our ClinTech and real-world data capabilities have been instrumental in guiding this program — from refining eligibility to contextualizing a single-arm dataset with a first-of-its-kind natural history study".

About FAP

FAP is one of the most clinically significant hereditary colorectal cancer syndromes and is caused by inactivating mutations in the APC gene, leading to the growth of hundreds to thousands of gastrointestinal polyps and a near 100% risk of developing colorectal cancer before the age of 40 if left untreated. With no approved pharmacotherapies, excisions followed sequentially by debilitating, life altering surgeries remain the only option to remove polyps and polyp burdened organs, typically involving colectomy in the early 20s. While this procedure removes immediate colon cancer risk, it does not address the underlying disease biology and does not prevent future polyp formation. Patients will continue to develop polyps in the rectum or upper GI tract, with approximately 50% of patients requiring subsequent life-altering surgical procedures to manage the persistent disease. Current treatment approaches lead to substantial long-term loss of quality of life, affecting continence, fertility, and long-term gastrointestinal function in relatively young patients. Approximately 90% of FAP patients go on to develop duodenal adenomas, with 6% eventually undergoing a high-morbidity risk duodenectomy to control polyp growth. FAP affects an estimated 50,000 individuals across the US and EU5 (France, Germany, Italy, Spain, and the UK).

Background on REC-4881 and Recursion’s Platform Insights

REC-4881 was discovered using one of the earliest versions of the Recursion OS (v0.1), through an unbiased, high-content AI-driven phenotypic screening approach in APC-deficient human cell models. Because FAP is driven by loss-of-function mutations in the APC gene, the platform was designed to identify molecules capable of rescuing APC-dependent biology—guided entirely by cellular phenotype, without presupposing any specific mechanism. Using AI/ML to extract and compare over a thousand morphological features that distinguish "diseased" from "healthy" states, the Recursion OS screened numerous investigative compounds and identified REC-4881 as one of the most robust phenotype-rescuing hits. In follow-up assays, REC-4881 consistently reverted APC-deficient cells toward a healthy-state phenotype and demonstrated potent, selective, and concentration-dependent MEK1/2 inhibition that was not seen across hundreds of other oncogenes and tumor suppressor models tested.

Importantly, the Recursion OS highlighted MEK1/2 inhibition as a mechanistic strategy to exploit a therapeutic vulnerability arising from APC loss in FAP—a disease area where MEK1/2 inhibition had not previously been investigated as a therapeutic strategy in a clinical setting. Based on this novel insight, Recursion in-licensed REC-4881 from Takeda, where it had been evaluated in solid tumors, and redirected it as the first MEK1/2 inhibitor advanced clinically for FAP. This program represents the power of a phenotype-first AI-driven discovery model: the platform surfaced a mechanistically aligned therapeutic opportunity solely through scaled high-dimensional exploration.

Today, the Company is using the Recursion OS 2.0 platform—including proprietary ClinTech capabilities of large-scale real-world evidence (RWE) analytics—to further advance the REC-4881 program. This includes a comprehensive natural history collaboration with Amsterdam University Medical Center, home to one of the largest and longest-running FAP registries, as well as analysis of more than 1,000 US FAP patients and 250,000 physician notes processed through Recursion’s custom LLM-based pipeline. Together, these data reinforce the relentlessly progressive nature of FAP, highlight the absence of spontaneous polyp regression, and demonstrate the substantial burden of repeated polyp-removal procedures and major surgeries experienced by real-world patients.

ClinTech insights also helped refine the design of the ongoing TUPELO trial, including expanding age eligibility from ≥55 to ≥18. This expansion was based on a thorough risk-benefit analysis, enabling evaluation of REC-4881 in younger patients who represent a substantial portion of FAP patients. REC-4881 has received Fast Track and Orphan Drug designations from the US FDA, as well as Orphan Drug designation from the European Commission.

Results of the Phase 2 Data for Ongoing REC-4881 Trial

Efficacy and Durability Findings
As of the November 25, 2025 data cutoff in the open-label Phase 2 portion of TUPELO, treatment with REC-4881 (4 mg QD) demonstrated meaningful and durable reductions in polyp burden in patients with FAP.
Week 13 Assessment
●REC-4881 produced a median 43% reduction in total polyp burden among 12 efficacy-evaluable patients.
●The majority of evaluable patients responded, with 75% showing reductions in polyp burden after 12 weeks of therapy.
●40% of patients (4 out of 10) achieved a ≥1-point improvement in Spigelman stage—a clinically meaningful measure of upper GI disease severity to assess surveillance and clinical management.
●Other investigational agents currently under evaluation in separate studies generated approximately 17–29% median reduction in polyp burden after 12 months of treatment; no off-treatment durability was reported (Biodexa press release, June 24 2024)

Week 25 Assessment
●After 12 weeks of treatment, patients went off treatment for an additional 12-weeks. Durability of effect was maintained during the off-treatment observation period with 82% of patients responding (>0% reduction; 9 out of 11) at Week 25.
●73% achieved durable ≥30% reductions in polyp burden with a 53% median reduction in total polyp burden observed.
●40% of patients (4 out of 10) maintained a ≥1-point improvement in Spigelman stage from baseline.

Safety Summary
As of the data cutoff, treatment with 4 mg REC-4881 demonstrated a safety profile generally consistent with prior MEK1/2 inhibitors.
●Across the combined Phase 1b and Phase 2 safety cohorts (n=19), 94.7% of patients reported at least one treatment-related adverse event (TRAE), the majority of which were Grade 1/2 in severity. The most frequent TRAEs (≥10%) included: dermatitis acneiform / rash and blood CPK increase.
●Grade 3 TRAEs occurred in 15.8% of patients; no Grade ≥4 TRAEs have been reported to date.
●Treatment modifications were infrequent, with 2 of 19 patients experiencing dose interruption.

About the TUPELO Trial Design and Expanded Population
The Phase 1b/2 TUPELO trial is evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of REC-4881 monotherapy in patients with familial adenomatous polyposis (FAP).
Study Design and Analysis
Efficacy is assessed via upper and lower endoscopy at baseline, Week 13 (on-treatment), and Week 25 (off-treatment).
●The primary endpoint is percent change from baseline in polyp burden, which is the sum of all polyp diameters in the GI.
●The Efficacy Evaluable Population includes patients with measurable disease at baseline who received ≥75% of study drug and had at least one post-baseline endoscopic assessment.
Disease staging uses the Spigelman system for upper GI polyposis and the InSiGHT classification for the lower GI tract.
Natural History Analyses
To better understand the natural history of FAP and to contextualize the single-arm efficacy of REC-4881, we collaborated with Amsterdam University Medical Center to analyze a registry of ~200 patients with FAP. 55 of these patients met the key inclusion criteria of TUPELO. We also leveraged our clinical development technology (ClinTech) platform to analyze US electronic health records (EHR), including physician notes, of ~1,000 FAP patients to assess disease progression and treatment patterns in the US. Both studies revealed high patient burden and progressive natural history of the disease. Results of the studies suggest that the natural history of FAP is to progress with relentless precancerous polyp progression: 87% of untreated patients in the registry experienced annualized increase in polyp burden. 10% were stable and 3% experienced a modest decrease in polyp burden. Mean increase of 60% and median increase of 28% in annualized polyp burden was observed. At least 75% of patients in the US EHR database had a major invasive surgery along with frequent polypectomies during follow-up.

Next Steps
Recursion plans to expand the population from ≥55 to ≥18 years old and further optimize dosing schedule. In parallel, the Company intends to engage the FDA in 1H26 to define a potential registration pathway.

(Press release, Recursion Pharmaceuticals, DEC 8, 2025, View Source [SID1234661271])