On June 12, 2025 Autolus Therapeutics plc (Nasdaq: AUTL), an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation programmed T cell therapies, reported updated long term data (up to approximately three years of follow up) from the FELIX study of obecabtagene autoleucel (obe-cel) in adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), to be presented in an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress between June 12-15, 2025, in Milan, Italy (Press release, Autolus, JUN 12, 2025, View Source [SID1234653855]). Autolus will also present an additional oral and poster presentation, the details of which are included below.

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"Obe-cel’s durability of response without any subsequent therapy in two out of every five responders is a key factor leading the transformation of therapy for adult r/r B-ALL patients. At a median follow up of 33 months, we are encouraged to see a continuation of the long-term plateau we observed at the last data cut," said Dr. Christian Itin, Chief Executive Officer of Autolus. "A well-tolerated, effective, durable treatment option for ALL patients who often have a poor prognosis and have had multiple prior treatments is of significant clinical benefit."

Oral S113:
Title: Can CAR T-cell therapy be a definitive treatment for adult r/r B-ALL without transplant? Long-term findings and predictors of sustained remission for obecabtagene autoleucel
Session Name: s447 Immunotherapy and CAR-T cells for ALL
Session room: Coral 6
Session Date and Time: Sunday, June 15; 11:00 – 12:15 CEST
Presenting Author: Jae H Park, MD

Summary: At the updated median follow up of 32.8 months, 38.4% of responders were in ongoing remission without consolidative SCT or other therapies (versus the previously reported 40% at a median follow up of 21.5 months). The 24-month probability of Event Free Survival was 43%, and for Overall Survival was 46%, with an emerging long-term plateau observed. A substantial subset of patients benefit from standalone treatment with obe-cel, achieving long-term remission. No new safety signals or Grade ≥3 secondary malignancies were observed at the extended follow-up. These results suggest that obe-cel may be a definitive treatment for some patients with r/r B-ALL – specific analysis will be needed to determine which patients may need additional treatments.

The multivariate analysis demonstrated that Philadelphia chromosome-positive disease, earlier obe-cel use, and relapsed disease correlated with achieving higher remission rates. Lower disease burden at lymphodepletion and ongoing CAR T-cell persistence were independent factors associated with long-term remission and survival.

Oral S114:
Title: Efficacy and Safety Outcomes of Obecabtagene Autoleucel (obe-cel) Stratified by Age in Patients with r/r B-ALL
Session Name: Immunotherapy and CAR-T cells for ALL
Session Room: Coral 6
Session Date and Time: Sunday, June 15; 11:00 – 12:15 CEST
Presenting Author: Bijal D. Shah, MD

Summary: Obe-cel treatment was associated with deep and durable remissions resulting in favorable overall remission rate, event free survival, and overall survival with low incidence of Grade ≥3 CRS and ICANS in both age groups (<55 years and ≥55 years). These findings indicate that obe-cel is effective and has a positive benefit and risk profile regardless of patient age, including in older adults with R/R B-ALL.

Poster PF378:
Title: Predicting Hematotoxicity Risk and Outcomes in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-All): Should Hematotox Models be CAR Specific Rather than Disease Specific
Session Title: Poster Session 1
Session date and time: Friday, June 13; 18:30 – 19:30 CEST.
Presenting Author: Claire Roddie, MD

Summary: Although both the CAR-Hematotox (CAR-HT) model, and the ALL-Hematotox (ALL-HT) model show potential, ALL-HT appears to improve risk stratification and may be a better predictor of response, survival and safety outcomes in adult patients with r/r B-ALL treated with obe-cel, than CAR-HT. Taken together with other published reports, our data suggest that the strength of HT-model predictions may be CAR T-cell product specific. Further analyses are needed.

On June 12, 2025 TheRas, Inc. d/b/a BBOT (the "Company"), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, reported the publication of preclinical data supporting the potential for BBO-10203 to provide therapeutic benefit across multiple tumor types (Press release, BridgeBio Oncology Therapeutics, JUN 12, 2025, View Source [SID1234653871]). The publication, titled "BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction" was published in the peer-reviewed journal Science.

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These data describe the discovery and preclinical evaluation of BBO-10203, a first-in-class, orally available inhibitor that selectively blocks the interaction between RAS proteins and PI3Kα without impairing insulin signaling. By covalently binding to a unique cysteine in the RAS-binding domain of PI3Kα, BBO-10203 effectively disrupts oncogenic RAS-driven activation of the PI3Kα pathway across a range of tumor types, including those with mutations in KRAS, PIK3CA, and HER2 amplification, without inducing hyperglycemia. The compound showed broad antitumor activity in vitro and in vivo and demonstrated enhanced efficacy when combined with targeted therapies such as CDK4/6 inhibitors, ER antagonists, HER2 inhibitors, and KRASG12C inhibitors. These findings support the potential of BBO-10203 as a well-tolerated, mechanistically distinct therapeutic for PI3Kα- and RAS-driven cancers.

"Because the contribution of the second most mutated signaling pathway in human cancers remains underappreciated, we searched for an entirely novel molecular mechanism that is not encumbered by known metabolic liabilities to inhibit PI3Kα signaling," said Pedro Beltran, PhD, Chief Scientific Officer of BBOT. "By blocking the crosstalk between RAS and PI3Kα in tumors, without interfering with physiological insulin signaling, we believe BBO-10203 represents a fundamentally differentiated approach with both biological and therapeutic promise."

"This work stemmed from our goal to elucidate the structural basis of RAS:PI3Kα binding and therapeutically target this interaction," said Dhirendra Simanshu, PhD, lead author and Principal Scientist at Frederick National Laboratory for Cancer Research (FNLCR). "Our findings show that targeting RAS-effector interactions is both structurally tractable and has potential across a range of cancers. BBO-10203 exemplifies a paradigm shift – rather than inhibiting RAS directly, it intercepts oncogenic signaling through effectors like PI3Kα, enabling tumor suppression while preserving essential physiological functions."

BBO-10203 is currently being evaluated in our Phase 1 BREAKER-101 study (NCT06625775) in patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS mutant advanced CRC, and KRAS mutant advanced NSCLC. The discovery of BBO-10203 was the result of a collaboration between the RAS Initiative at Frederick National Laboratory, Lawrence Livermore National Laboratory, and BBOT.

"This work is an excellent example of chemistry bringing clarity to biology," said Frank McCormick, PhD, FRS, Chairman of the BBOT Board, Advisor to the National Cancer Institute’s RAS Initiative at Frederick National Laboratory for Cancer Research, and Professor of Tumor Biology and Cancer Research at UCSF. "The role of the RAS:PI3Kα interaction in cancer biology has long been suspected but challenging to pin down precisely. Now we understand which cancers depend on this interaction, some quite unexpected. With BBO-10203 now in the clinic, there’s real hope that these discoveries will translate into meaningful benefit for many cancer patients."

On June 12, 2025 Bristol Myers Squibb (NYSE: BMY) reported the presentation of new data from its targeted protein degradation platform during the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress being held from June 12-15 in Milan, Italy (Press release, Bristol-Myers Squibb, JUN 12, 2025, View Source [SID1234653840]). Presentations feature updated clinical findings on the company’s investigational oral CELMoD agents mezigdomide and iberdomide in multiple myeloma, and golcadomide in non-Hodgkin lymphoma, as well as the first results evaluating the company’s first-in-class, oral BCL6 ligand-directed degrader (LDD) (BMS-986458) in non-Hodgkin lymphoma.

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The latest data presented for the three lead CELMoD agents and BCL6 LDD underscore the potential impact that these therapies may have in addressing significant unmet medical needs in hematologic malignancies. These agents are part of continuing research across targeted protein degradation at Bristol Myers Squibb, which also encompasses additional CELMoD agents, LDDs and degrader antibody conjugates (DACs) across blood cancers and solid tumors, as well as non-malignant hematologic disorders.

Protein degraders, like CELMoD agents and LDDs, are therapies designed to target and degrade specific proteins that drive diseases, including many proteins that are difficult to target through conventional small-molecule inhibitors. These innovative agents have the possibility to enhance the efficacy of existing therapies and overcome resistance in various malignancies, potentially improving patient outcomes.

"As a leader in the field of targeted protein degradation, we are committed to applying our decades of expertise to the development of these next wave of agents. The efficacy and safety data presented at the EHA (Free EHA Whitepaper) Annual Meeting this year is promising and reinforces the potential of CELMoD agents in combination with other standard treatments," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology and Cell Therapy for Bristol Myers Squibb. "These analyses also add to the body of evidence for these programs as we continue pivotal studies for each of the agents that we anticipate reading out in the next year and onwards."

Key targeted protein degradation data being presented by Bristol Myers Squibb at the EHA (Free EHA Whitepaper) Annual Congress include:

Mezigdomide (MEZI):

Abstract #4160130: Updated results were presented from the dose-escalation phase of the MM-002 study for the combinations of mezigdomide, dexamethasone, and bortezomib (Cohort A MeziVd; n=28), and mezigdomide, dexamethasone, and carfilzomib (Cohort C MeziKd; n=27) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 2–4 prior therapies:

Overall response rate (ORR) was 75.0% for Cohort A and 85.2% for Cohort C, respectively.
Median (95% CI) duration of response (DOR) for Cohort A and Cohort C was 10.9 (8.8–18.7) and 11.9 (6.4–35.9) months, respectively.
Median (95% CI) progression-free survival (PFS) for Cohort A and Cohort C was 12.3 and 13.5 months, respectively.
Results from the dose-expansion cohort (Cohort D) of the study were also presented for the MeziVd combination (n=49) in patients with RRMM who had received 1–3 prior therapies:

ORR was 85.7%
Median (95% CI) DOR was 19.4 months (9.7-NA)
Median PFS (95% CI) was 17.5 months
The most common grade 3/4 treatment-emergent adverse event (TEAE) across arms was neutropenia and was managed with G-CSF and dose modifications.

Abstract #4160802: New data was presented evaluating mezigdomide in all-oral triplet combinations with other oral novel agents in RRMM.

Results showed that the ORR was:
50% for mezigdomide plus EZH2 inhibitor tazemetostat and dexamethasone (n=16)
35% for mezigdomide plus BET inhibitor BMS-986158 and dexamethasone (n=20)
80% for mezigdomide plus MEK inhibitor trametinib and dexamethasone (n=20)
The most frequent grade 3/4 TEAE was neutropenia, and grade 3/4 nonhematologic TEAEs were low.
A separate analysis(Abstract #4160749) showed that these combinations lead to the activation and proliferation of NK and T cells, including in patients previously treated with T cell-redirecting therapies.
Iberdomide (IBER):

Abstract #4160144: Updated results were presented from MM-001, evaluating the combination of iberdomide, bortezomib, and dexamethasone (IberVd) in patients with transplant-ineligible, newly diagnosed multiple myeloma (NDMM), confirming durable, deep responses in the study.

At a median follow-up of 25 months, the ORR in the intent-to-treat (ITT) population (n=18) was 88.9%, with 66.6% having a complete response or better.
44% of patients in CR achieved minimal residual disease (MRD) negativity at a sensitivity of 10-5.
The most common hematologic grade 3/4 TEAE was neutropenia (29.4%); 2 (11.8%) patients had grade 3/4 peripheral neuropathy. Overall, the most common grade 3/4 TEAEs were infections (47.1%).
Golcadomide (GOLCA):

Abstract #4160953: Updated results were presented from a study evaluating golcadomide with or without rituximab for the treatment of R/R follicular lymphoma (FL). Patients with R/R FL who had received ≥2 prior lines of treatment received golcadomide monotherapy in the dose-escalation part of the study (Part A), followed by golcadomide once daily at 0.2 or 0.4 mg with or without rituximab in the expansion part (Part B). Results continued to show promising efficacy with durable responses in heavily pre-treated patients with R/R FL.

In Part A, the ORR was 67%, with a complete response rate (CRR) of 42% for patients treated with golcadomide monotherapy.
In Part B, the ORR was 94% and the CRR was 63% for patients treated with golcadomide 0.4mg + rituximab. The median DOR was 4.8 months at a median follow-up of 5.75 months. Responses were consistent in patients who received prior lenalidomide-based and/or T cell-redirecting therapy.
The most common grade 3/4 treatment-related adverse events across dose levels in Part B (n=60) were neutropenia and anemia, occurring in 60% and 13% of patients, respectively. No patients discontinued therapy due to side effects related to golcadomide. Non-hematologic side effects were infrequent and mostly low-grade.
Abstract #4161005: Updated results were presented from a study evaluating golcadomide with or without rituximab for the treatment of R/R diffuse large b-cell lymphoma (DLBCL). Patients received golcadomide once daily at either 0.2 mg (n=39) or 0.4 mg (n=38). Results continued to show durable responses in heavily pre-treated patients with R/R DLBCL and a consistent safety profile.

For patients treated with golcadomide 0.4mg + rituximab, the ORR was 58% and the CRR was 44%, with a median DOR of 14.5 months. Among patients who had prior T cell–redirecting therapy, the ORR was 56%, and the CRR was 38%.
The most common grade 3/4 treatment-related adverse events across dose levels (n=77) were neutropenia and anemia, occurring in 64% and 20% of patients, respectively. Most adverse events were manageable, with discontinuation due to AE occurring in 7% of patients.
Based on the results of early studies, mezigdomide, iberdomide and golcadomide are being evaluated in multiple phase 3 studies:

SUCCESSOR-1: mezigdomide, bortezomib, and dexamethasone vs. pomalidomide, bortezomib, and dexamethasone in patients with RRMM (projected data in 2026)
SUCCESSOR-2: mezigdomide, carfilzomib, and dexamethasone vs. carfilzomib and dexamethasone in patients with RRMM (projected data in 2026)
EXCALIBER RRMM: iberdomide, daratumumab, and dexamethasone vs. daratumumab, bortezomib, and dexamethasone in patients with RRMM (projected MRD data in 2025)
EXCALIBER Maintenance: iberdomide maintenance vs. lenalidomide maintenance following autologous stem cell transplant in patients with NDMM (projected data in 2029)
GOLSEEK-1: golcadomide and R-CHOP chemotherapy vs. placebo and R-CHOP in patients with previously untreated high-risk LBCL (projected data in 2028)
GOLSEEK-4: golcadomide and rituximab vs. investigator’s choice in patients with R/R FL who received at least 1 prior systemic therapy (projected data in 2030)
BMS-986458 BCL6 LDD:

Abstract #4160340: First clinical findings were presented from the dose-escalation part of the first-in-human, multicenter, open-label study of BMS-986458 in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Initial results evaluating 31 heavily pre-treated patients treated with BMS-986458 were promising and support continued development for the treatment of NHL.

BMS 986458 was well-tolerated, with the most common treatment-related adverse events (TRAEs) being grade 1/2 arthralgia (19.4%) and fatigue (16.1%); no grade ≥3 treatment-related cytopenias or treatment-related discontinuations were observed.
Rapid and sustained degradation of BCL6 was demonstrated in peripheral blood and in the tumor at all doses evaluated.
Antitumor activity was evident from the first dose level in DLBCL and FL patients. Among 21 efficacy-evaluable patients, the ORR was 81% (N=17), and CRR was 23.8% (N=5).

On June 12, 2025 Specialised Therapeutics (ST) reported the expansion of its existing supply and distribution agreement with Incyte Biosciences International Sàrl, the Swiss-based affiliate of Incyte (NASDAQ:INCY), to launch and distribute two additional medicines from its oncology portfolio in Australia, New Zealand and Singapore, with an option to add further countries in the Asia-Pacific region (Press release, Specialised Therapeutics Australia, JUN 12, 2025, https://www.prnewswire.com/news-releases/specialised-therapeutics-expands-partnership-with-incyte-to-include-two-additional-therapies-for-hard-to-treat-conditions-302479723.html [SID1234653856]). The expanded agreement will see new therapies axatilimab (registered as Niktimvo in the United States) and retifanlimab (registered as Zynyz in the U.S. and European Union) added to the current partnered portfolio of Minjuvi (tafasitamab) and Pemazyre (pemigatinib).

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Under the terms of the expanded agreement, Incyte will be responsible for the development, manufacture and supply of both axatilimab and retifanlimab to the region, while ST will have responsibility for regulatory, distribution and local marketing and medical affairs related activities.

ST Chief Executive Officer, Mr Carlo Montagner, welcomed the expansion of the partnership agreement with Incyte, a leading global biopharmaceutical company, and the opportunity to bring these important medicines to eligible patients in the local region.

"Specialised Therapeutics has partnered with Incyte since 2021 and we are delighted to be extending this successful partnership," he said. "As part of our initial agreement, our teams have worked collaboratively to commercialise Minjuvi, which has been approved for use in Australia, and Pemazyre, which has been approved in Australia and Singapore, and we look forward to expanding the portfolio to help more patients with rare and hard-to-treat conditions."

"The addition of axatilimab and retifanlimab to the partnership agreement with Incyte recognises our strong track record of working with local stakeholders to bring innovative medicines to patients where unmet medical needs persist, despite the availability of existing treatments," said Mr Montagner. "Our focus will be on seeking regulatory and reimbursement approval for all four medicines in the region, to ensure equitable access to these treatments are available for patients as soon as practicable."

ST anticipates submitting axatilimab and retifanlimab for local regulatory and reimbursement approval in 2025.

Incyte CEO, Mr Hervé Hoppenot said the expanded partnership agreement reflected the synergies between the two companies, with a shared goal of improving outcomes for patients with unmet medical needs.

"We are pleased to extend our partnership with ST to include axatilimab and retifanlimab," he said. "ST has already demonstrated its ability to navigate complex regional regulatory pathways for Minjuvi and Pemazyre, and we look forward to continuing our work together to make these new therapies available for the oncology community in the Asia-Pacific region."

Axatilimab is a first-in-class colony stimulating factor-1 receptor (CSF-1R)-blocking antibody. It was approved by the US Food and Drug Administration (FDA) in August 2024 as a treatment for adults and children with chronic graft-versus-host disease (GVHD) who have received at least two prior treatments (systemic therapy) and require additional treatment.1 Chronic GVHD usually occurs 3 months after a transplant – typically haematopoietic stem cell or bone marrow transplantation, but occasionally also solid organ transplants – where the donor cells ("graft") attack the graft recipient’s cells ("host").2 Chronic GVHD can affect all organs, but commonly impacts the skin, mouth, eyes, lungs, stomach, bowel, and liver.2,3 The Phase II clinical trial for axatilimab involved 79 patients from 13 countries, including Australia and Singapore.4

Retifanlimab is an intravenous immune checkpoint (PD-1) inhibitor that has been approved in the US in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) and as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression or intolerance to platinum-based chemotherapy.5 Retifanlimab is also approved in the US6 and Europe7 for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). MCC is a rare and aggressive type of skin cancer, that is often difficult to diagnose due to the lack of specific features to distinguish it from other common skin cancers.8 Australia has the highest incidence of MCC in the world.9 The pivotal Phase II clinical trial of retifanlimab in MCC enrolled 101 chemotherapy-naïve patients from 12 countries, including Australia.10 In addition to MCC, retifanlimab, in combination with chemotherapy, is currently being investigated as a potential therapeutic option in other hard-to-treat cancers, including metastatic non-small cell lung cancer (NSCLC).

On June 12, 2025 Disc Medicine, Inc. (NASDAQ:IRON), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases, reported 5 posters presented at the EHA (Free EHA Whitepaper) 2025 annual meeting in Milan, Italy (Press release, Disc Medicine, JUN 12, 2025, View Sourcenews-releases/news-release-details/disc-medicine-presents-positive-clinical-data-updates-across" target="_blank" title="View Sourcenews-releases/news-release-details/disc-medicine-presents-positive-clinical-data-updates-across" rel="nofollow">View Source [SID1234653841]). This year’s presentations included data from HELIOS, an ongoing open-label extension study of bitopertin in EPP, which showed favorable long-term efficacy and safety with sustained protoporphyrin IX (PPIX) reductions, improvement in quality of life, and improved liver biomarkers. Disc is advancing development and registrational activities for bitopertin in EPP, with plans to submit an NDA in H2 2025. The company has initiated APOLLO, a confirmatory clinical trial of bitopertin in adults and adolescents with EPP. Disc recently launched a campaign to raise awareness of EPP among physicians, patients, and caregivers with emphasis on the causative role of PPIX accumulation in the disease. Learn more at PPIXisWhy.com.

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Disc also presented longer term data from the continuation phase of its Phase 1b trial in MF anemia, showing sustained activity on key biomarkers and durable anemia response among major responders. Enrollment for the Phase 2 RALLY-MF trial of DISC-0974 is ongoing with the exploratory cohort for patients on concomitant momelotinib or pacritinib fully enrolled. The company expects to present initial RALLY-MF data in H2 2025. Additionally, Disc shared an update of the Phase 1 healthy volunteer trial of DISC-3405, initially presented at ASH (Free ASH Whitepaper) 2024, which demonstrated deep, sustained reductions in serum iron and meaningful changes in hematologic parameters, establishing proof of mechanism. Based on these data, the company has initiated a Phase 2 trial of DISC-3405 in polycythemia vera (PV). Disc also presented an iron pulse study of DISC-3405 in healthy volunteers which showed inhibition of dietary iron uptake, further confirming the mechanism of action and supporting DISC-3405’s potential in diseases of iron overload.

The collection of data presented at EHA (Free EHA Whitepaper) adds to the evidence base supporting Disc’s continued advancement of all three clinical candidates and provides support for expansion opportunities in new indications. Management will host a call to review these updates on June 16 at 8:00 am ET. Please register for the event on the Events and Presentations page of Disc’s website (View Source)

Bitopertin, DISC-0974, and DISC-3405 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide.

Summary of Poster Presentations

Bitopertin:

HELIOS:

HELIOS is an ongoing Phase 2, open-label, long-term extension trial that enrolled 86 adult and adolescent patients with EPP from the BEACON and AURORA trials. Patients were randomized to receive 20 mg or 60 mg bitopertin in BEACON and 20 mg or 60 mg bitopertin or placebo in AURORA, with all patients transitioning to a 60 mg daily dose of bitopertin in HELIOS.

Longer term treatment with bitopertin was associated with sustained reductions in the disease-causing toxin PPIX, with additional benefit for patients receiving the 60 mg dose continuously
Continuous treatment with 60 mg of bitopertin reduced ALT and other exploratory hepatobiliary biomarkers
Nearly all participants reported substantial improvements in quality of life measures
Bitopertin exhibited a favorable longer-term safety profile with up to 2+ years of exposure and similar safety across adults and adolescents with EPP and XLP
DISC-0974:

DISC-0974 Phase 1b in MF anemia:

Data from the continuation phase of the Phase 1b trial of DISC-0974 in MF anemia as of October 2024 were presented. This multi-center, open-label trial included patients who were: non-transfusion dependent receiving no transfusions (nTD, n=23), transfusion dependent with low transfusion burden (TD Low, n=5) and transfusion dependent with high transfusion burden (TD High, n=7). The trial was comprised of both patients receiving concomitant JAK inhibitor therapy (n=13) and not receiving JAK inhibitor therapy (n=22). DISC-0974 was administered subcutaneously at 14 mg (n=1), 28 mg (n=7), 50 mg (n=12), 75 mg (n=9), or 100 mg (n=6) every 4 weeks for up to 6 treatments. Long-term results demonstrated:

Sustained hepcidin suppression, iron mobilization, and reduction in Zinc PPIX, a measure of iron restricted hemoglobin production
nTD patients:
50% of evaluable patients achieved major response of sustained mean hemoglobin increase of ≥1.5 g/dL
Hematologic improvement was durable through the continuation phase
TD Low patients:
80% of evaluable patients achieved major response of transfusion independence over 16 weeks
Hematologic improvement was durable, and all major responders remained transfusion independent during the continuation phase
TD High patients:
40% of evaluable patients achieved major response of transfusion independence over 12 weeks
1 of 2 patients with a major response entered the continuation phase and remained transfusion independent at Day 225, with follow-up ongoing
DISC-0974 was safe and well-tolerated at all evaluated dose levels
DISC-0974 in combination with luspatercept and ESA (mouse model):

The effect of DISC-0974, luspatercept, and ESA as single agents and DISC-0974 combined with luspatercept or ESA on hematological parameters in wild type mice was evaluated. Results showed:

Treatment with DBIO-100 (a mouse analog of DISC-0974) suppressed hepcidin, enhanced iron availability, and boosted erythropoiesis in wild-type mice
Combining with DPO (ESA) or RAP-536 (mouse analog of luspatercept) led to additional hematological benefits beyond those agents alone
These results demonstrate that DISC-0974 has a distinct mechanism of action among anemia-targeted agents and highlight the potential for synergistic anemia benefits when combining DISC-0974 with other anemia-targeted agents.

DISC-3405:

Phase 1 Healthy Volunteer Study:

Updated SAD/MAD data from the Phase 1 trial of DISC-3405 in healthy volunteers were presented. In the SAD portion of this trial, healthy males and females ages 18 to 65 were given a single dose of placebo (n=10) or DISC-3405 at 75 mg intravenously (IV) (n=6), 37.5 mg subcutaneously (SC) (n=6), 75 mg SC (n=6), 150 mg SC (n=6), or 300 mg SC (n=6). The MAD portion included placebo (n=4), 75 mg SC (n=6), and 150 mg SC (n=6) cohorts dosed every 4 weeks for a total of 2 doses. Consistent with data presented at ASH (Free ASH Whitepaper) 2024, results showed:

DISC-3405 produced dose-related increases in serum hepcidin with corresponding reductions in serum iron across all dose levels
DISC-3405 resulted in deep reductions in serum iron (ranging from 50-80% from baseline) that were sustained and support a once-monthly SC dosing regimen
Single and repeat dosing of DISC-3405 demonstrated meaningful reductions in hematologic parameters, including reticulocyte hemoglobin, hemoglobin, and hematocrit
DISC-3405 was generally well-tolerated at all evaluated dose levels, with no serious adverse events (AEs), greater than Grade 2 AEs, or AEs leading to study withdrawal
These results provide proof of mechanism and support the advancement DISC-3405 into proof of concept studies. Disc has now initiated a Phase 2 trial of DISC-3405 in PV with initial results expected in 2026.

Iron Pulse Study:

Disc conducted an iron pulse study in healthy volunteers to evaluate the effectiveness of DISC-3405 in inhibiting dietary iron uptake. N=8 healthy volunteers received placebo treatment followed by oral ferrous sulfate tablets on two sequential occasions to establish baseline iron absorption profiles. Participants were then given a single 150mg IV dose of DISC-3405, followed by oral ferrous sulfate "iron pulses" on the 2nd and 15th days following treatment. DISC-3405 resulted in an average 94% reduction in iron absorption at Day 2 and 68% at Day 15.

These results confirm the mechanism of DISC-3405 and demonstrate its ability to block dietary iron absorption, supporting the potential for treating diseases associated with iron overload.