On June 12, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported positive clinical data from the Company’s ongoing NX-5948-301 study, a Phase 1a/b clinical trial of bexobrutideg (NX-5948) in patients with relapsed or refractory B-cell malignancies (Press release, Nurix Therapeutics, JUN 12, 2025, View Source [SID1234653846]).

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The data include findings from the fully enrolled Phase 1a dose escalation study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and the ongoing Phase 1a/1b cohorts of patients with Waldenström macroglobulinemia (WM). Talha Munir, M.B. Ch.B, Ph.D., consultant hematologist at Leeds Teaching Hospitals NHS Trust, deputy chair of the United Kingdom National Cancer Research Institute CLL Study Group, and Dima El-Sharkawi, M.B., B.S., M.A., Ph.D., MRCP FRCPath, Consultant Haematologist, Royal Marsden NHS Foundation Trust, Sutton, U.K., will present these data at the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA2025), taking place June 12–15, 2025, in Milan, Italy.

"These data demonstrate an impressive safety and efficacy profile for bexobrutideg with improvement in responses in patients over time, including the notable achievement of a complete response in a patient with CLL and a history of two lines of prior therapy who has been on bexobrutideg treatment for over two years," said Dr. Munir. "Patients with relapsed or refractory CLL and WM who have failed treatments with commonly prescribed BTK inhibitors and other agents due to intolerance or acquired resistance have few therapeutic options. Nurix’s bexobrutideg has the potential to address this unmet need and provide a life-changing treatment for patients with CLL and WM."

"With longer time on treatment, we are encouraged by the continued favorable safety profile and high ORR with deepening responses in CLL and WM, including those with clinical and genomic high risk features including CNS involvement," said Paula G. O’Connor, M.D., chief medical officer of Nurix. "We have further expanded our Phase 1b cohorts in select CLL populations and remain on track to initiate pivotal studies in 2025."

"Bexobrutideg offers a next-generation approach to BTK targeting with exquisite selectivity, superior preclinical potency, broad coverage of mutations and demonstrated clinical activity in areas of high unmet medical need," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We are not only preparing to initiate pivotal studies in the coming months but are also laying the foundation for the commercialization of bexobrutideg as a differentiated treatment option for patients with B-cell malignancies."

Data presented at EHA (Free EHA Whitepaper)2025 include efficacy and safety findings for patients with CLL/SLL in the fully enrolled Phase 1a dose escalation study (n=48). This cohort of CLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 2–12) including prior covalent BTK inhibitors (97.9%), prior BCL2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (27.1%). At baseline, many patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (38.3%) and PLC2G (14.9%). Poor prognostic features were common, including TP53 mutations (44.7%), and five patients (10.4%) had central nervous system (CNS) involvement.

Patients were treated with bexobrutideg at doses ranging from 50 mg to 600 mg once daily by oral administration in the Phase 1a dose escalation study. As of the March 12, 2025 data cut, the median follow up was 9.0 months with most patients still on treatment. Bexobrutideg was well tolerated across all doses evaluated with the most common treatment emergent adverse events of purpura/contusion (45.8%), neutropenia (29.2%) and thrombocytopenia (22.9%), primarily low grade. No new onset atrial fibrillation was observed. Among the efficacy evaluable patients with CLL (n = 47), bexobrutideg treatment resulted in a robust objective response rate (ORR) of 80.9% across all doses tested with a median time to first response of 1.9 months. Many patients experienced deepening of their response with longer time, with multiple conversions from stable disease to partial responses and one patient, who has been on treatment for over two years, experienced a complete response. The median duration of response has not been reached, with 18 patients on treatment for more than a year. Responses were observed across all populations regardless of prior treatment, baseline mutations, or CNS involvement.

The data presented at EHA (Free EHA Whitepaper) included patients with WM (n=22) treated with bexobrutideg at doses ranging from 50 mg to 600 mg once daily by oral administration from both the Phase 1a dose escalation and Phase 1b cohort expansion. Among the 22 WM patients, the median age was 72.5 years (range 58-86 years) and the median number of prior lines of therapy was 3 (range 2-5). All 22 patients previously had been treated with a covalent BTK inhibitor (100%), 21 had received prior chemotherapy/chemo-immunotherapy (95.5%), four had received prior non-covalent BTK inhibitor (18.2%), and one patient (4.5%) had received prior treatment with a BCL2 inhibitor. Baseline mutation status in MYD88 and CXCR4 was captured from patient records. 15 patients (68.2%) had mutations in MYD88, and five patients (22.7%) had mutations in CXCR4. Bexobrutideg was well tolerated in patients with WM with a profile that was consistent with the overall study population and previous disclosures. Adverse events (AEs) were predominantly low grade; with the most common being petechiae (27.3%), diarrhea (22.7%), purpura/contusion (18.2%), neutropenia (18.2%), and thrombocytopenia (18.2%). There were no dose limiting toxicities observed and no grade 5 AEs. Two treatment emergent AEs led to drug discontinuation. No new onset atrial fibrillation was observed.​ As of the March 12, 2025 data cut, 19 patients were evaluable for responses. Objective response was observed in 16 patients (84.2%), including two patients (10.5%) with very good partial response (VGPR), 11 patients (57.9%) with partial response (PR), and three patients (15.8%) with minor response (MR). Three patients (15.9%) had a best response of stable disease (SD). Responses were observed in patients regardless of their baseline mutations in MYD88 and CXCR4. Steady reductions in IgM levels were observed starting from the first assessment at four weeks, which continued to deepen, and three patients achieved IgM reductions of greater than 90%.

Conference Call Details
On June 12, 2025, at 8:00 a.m., ET (2:00 p.m., CEST), Nurix will host a conference call and webcast to discuss data from the bexobrutideg clinical trial. The live webcast, with an accompanying presentation, will be accessible under the Events and Presentations page in the Investors section of the company’s website here. To participate in the live conference call, the dial-in number in the United States is 877-346-6112. For participants outside the United States, the dial-in number is 1-848-280-6350. A replay of the webcast and call will be archived on the Nurix website for approximately 30 days after the event.

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. Bexobrutideg is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).

On June 12, 2025 Nona Biosciences, a global biotechnology company providing integrated solutions from "Idea to IND" (I to ITM), reported a license agreement with Visterra, Inc. to advance Visterra’s next-generation biotherapeutic pipeline for immune-mediated and autoimmune diseases, leveraging Nona’s proprietary HCAb Harbour Mice technology platform (Press release, Nona Biosciences, JUN 12, 2025, View Source [SID1234653845]).

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Nona’s HCAb Harbour Mice platform enables the generation of fully human heavy-chain-only antibodies (HCAbs), offering key advantages such as reduced immunogenicity and enhanced versatility for next-generation biotherapeutics. This innovative platform has been clinically validated and widely recognized by global partners.

"We are pleased to collaborate with Visterra and support the development of their biotherapeutic pipeline," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences. "This collaboration reflects our commitment to advancing biotherapeutic innovation. By leveraging our fully human HCAbs, we aim to unlock new therapeutic possibilities and accelerate the development of transformative medicines for patients worldwide."

On June 12, 2025 Kura Oncology, Inc. (Nasdaq: KURA, "Kura") and Kyowa Kirin Co., Ltd. (TSE: 4151, "Kyowa Kirin") reported positive updated clinical data from KOMET-007, a Phase 1a/1b trial of ziftomenib, a highly selective oral investigational menin inhibitor, in combination with standards of care in patients with newly diagnosed NPM1-mutant (NPM1-m) and KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) (Press release, Kura Oncology, JUN 12, 2025, View Source [SID1234653844]). The data for the combination with cytarabine/daunorubicin (7+3) were presented as an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress (EHA2025) being held in Milan, Italy from June 12-15, 2025.

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"The findings presented at EHA (Free EHA Whitepaper)2025 underscore the potential of ziftomenib in combination with 7+3 as an early intervention in the frontline setting of AML and could offer a meaningful opportunity to improve patient outcomes," said Harry Erba, M.D., Ph.D., Director of the Leukemia Program at the Duke Cancer Institute. "The high rates of complete remission and MRD negativity across the 7+3 cohorts are particularly encouraging. The continued rapid enrollment in the Phase 1b portion of this study underscores the urgency and enthusiasm for further evaluating this combination approach."

"We remain very encouraged by the updated clinical activity, safety and tolerability data from the KOMET-007 study evaluating ziftomenib with 7+3 in newly diagnosed AML patients with NPM1 mutations or KMT2A rearrangements," said Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology. "These updated data reinforce the combination potential of ziftomenib in the frontline setting, strengthening our confidence in its ability to provide a valuable treatment option for a significant portion of the AML population. We and our partners at Kyowa Kirin are working in earnest to prepare for the KOMET-017-IC and NIC pivotal Phase 3 studies, which will enable us to test ziftomenib-based combinations and their potential, if approved, to transform care for AML patients worldwide."

In the ongoing study, ziftomenib dosed once daily at 600 mg in combination with 7+3 continued to demonstrate robust and evolving clinical activity in patients with newly diagnosed AML. Among 71 response-evaluable patients, 92% (65/71) achieved a composite complete remission (CRc) (93% for NPM1-m, 89% for KMT2A-r patients) and 80% (57/71) achieved a complete remission (CR) (84% for NPM1-m, 74% for KMT2A-r patients) at the time of data cutoff. A rate of CR minimal residual disease (CR-MRD) negativity of 71% for NPM1-m with a median time to MRD negativity of 4.7 weeks and a rate of CR-MRD negativity of 88% for KMT2A-r patients with a median time to MRD negativity of 4.4 weeks were observed. Ziftomenib did not delay time to neutrophil and platelet count recovery, which was comparable to intensive chemotherapy regimens.

Median follow-up times for the two populations were 24.9 weeks (range 4.3-47.1) in NPM1-m patients and 15.7 weeks (range 1.1-40.3) in KMT2A-r patients. Among response-evaluable NPM1-m patients, neither a median duration of CR nor a median overall survival (OS) had been reached. Among response-evaluable KMT2A-r patients, a median duration of CR was determined to be 25.6 weeks (95% CI, range 8.3-NE), and a median OS had not been reached. Notably, 96% (47/49) of NPM1-m patients and 88% (29/33) of KMT2A-r patients remained alive and on study.

The safety population included 82 newly diagnosed adult patients with NPM1-m or KMT2A-r AML from the pooled Phase 1a/1b portions of the trial at the 600 mg QD dose of ziftomenib. The safety profile observed with ziftomenib was consistent with previously reported data. Ziftomenib-related adverse events (TRAEs) of ≥ Grade 3 (Gr3), which occurred in more than 10% of patients were febrile neutropenia (15%), decreased platelet count (15%), anemia (11%) and decreased neutrophil count (11%). One case of differentiation syndrome (KMT2A-r, Gr3) was successfully managed by protocol-specified mitigation strategies. Two cases of investigator-assessed QTc prolongation (both KMT2A-r, Gr3) were reported; both patients were on other medications (posaconazole and/or piperacillin/tazobactam), which have been identified as potentially causing QT prolongation at the time of QT assessment. No dose-limiting toxicities, drug-drug interactions, clinically meaningful ziftomenib-associated QTc prolongation or additive myelosuppression were observed.

"Despite the availability of approved therapies for AML, up to 70% of patients who initially achieve a complete response relapse within three years – highlighting a substantial unmet need," said Takeyoshi Yamashita, Ph.D., Executive Vice President and Chief Medical Officer of Kyowa Kirin. "The data presented at EHA (Free EHA Whitepaper)2025 suggest a favorable safety, tolerability, and efficacy profile for ziftomenib. We are encouraged by its potential as a future first-line treatment option and are committed to advancing the KOMET-017 Phase 3 trial, expected to begin later this year, to further evaluate its value in AML care."

The EHA (Free EHA Whitepaper)2025 oral presentation highlighting ziftomenib combined with 7+3 in newly diagnosed (1L) NPM1-m and KMT2A-r AML, and an encore presentation of results from the KOMET-001 registrational trial of ziftomenib in relapsed/refractory (R/R) NPM1-m AML (also presented during EHA (Free EHA Whitepaper)2025) are available in the Posters and Presentations section of the Kura website. The KOMET-017 protocol consists of 2 separate Phase 3 studies, which will investigate the benefits and risks of adding ziftomenib to standards of care treatments in patients newly diagnosed NPM1-m or KMT2A-r AML and which is registered at www.clinicaltrials.gov as NCT07007312.

Virtual Investor Event

Kura will host a virtual investor event featuring company management and investigators from the KOMET-007 trial of ziftomenib in combination with 7+3 in patients with NPM1-m and KMT2A-r AML at 4:30pm ET / 1:30pm PT on Wednesday, June 18, 2025. Those who would like to participate may access the live webcast here, or register in advance for the teleconference here. The event can also be accessed on the Investors section of Kura’s website at www.kuraoncology.com. An archived replay will be available shortly after the conclusion of the live event.

On June 12, 2025 Enterome SA, a clinical-stage company developing first-in-class OncoMimics immunotherapies to treat cancer, reported it has raised $19 million in a new private financing to advance its lead clinical program EO2463 OncoMimics immunotherapy to treat indolent non-Hodgkin lymphoma (iNHL) (Press release, Enterome, JUN 12, 2025, View Source [SID1234653842]). The new funds will be used to expand and finalize the ongoing Phase 1/2 SIDNEY clinical trial of EO2463 and prepare the candidate for a registrational trial.

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New U.S. investor The Institute for Follicular Lymphoma Innovation (IFLI), a global non-profit foundation dedicated to advancing research and treatment for follicular lymphoma, invested $9 million in the round, of which $5 million will be allocated to Enterome upon closing and an additional $4 million in conditional tranched funding.

Existing shareholders invested an additional $10 million including: SymBiosis, a U.S. venture capital firm; Seventure Partners, based in France; Lundbeckfonden BioCapital from Denmark; Primo Capital, an Italian venture capital and private equity firm; and The U.S. Leukemia & Lymphoma Society Therapy Acceleration Program (LLS TAP).

"Attracting highly specialized blood cancer investor IFLI to this financing demonstrates the conviction of our new and existing investors in the potential of OncoMimics for blood and solid tumor cancers," said Pierre Bélichard, Enterome’s Chief Executive Officer. "We currently are generating exciting clinical proof of concept data for EO2463 monotherapy in several iNHL patient populations included in the Phase 1/2 SIDNEY clinical trial. Most importantly, EO2463 has shown robust clinical efficacy and exceptional safety and tolerability – which is especially impressive for such a potent immunotherapy. This offers a new hope for these patients and a rare opportunity to create an entirely new market segment for an impactful therapeutic. This financing will enable us to continue the SIDNEY trial of EO2463 and prepare to launch a first pivotal Phase 3 trial of this candidate for the ‘watch-and-wait’ iNHL population."

The company presented interim SIDNEY dataat the American Society of Hematology (ASH) (Free ASH Whitepaper) conference in December 2024, showing highly encouraging responses in the Cohort 2 of "watch and wait" iNHL patients in the ongoing SIDNEY study. This population, as the name suggests, is generally not eligible to receive other treatments due to the unacceptable risk-benefit ratio (in this iNHL sub-population) of the most commonly used blood cancer therapies.

The company also recently disclosed having held positive meetings with both FDA (Type C meeting) and EMA (Scientific Advice), outlining a clear regulatory path to registration for marketing authorizations in "watch-and-wait" iNHL.

"This investment aligns with IFLI’s mission to accelerate the development of innovative therapies and precision biomarkers for follicular lymphoma," said Michel Azoulay, MD, Chief Medical Officer at IFLI. "EO2463 represents a novel class of synthetic, off-the-shelf Immunotherapeutics with a unique mechanism of action that selectively targets malignant B cells. We are particularly interested in supporting Enterome’s efforts to demonstrate EO2463’s clinical efficacy across multiple lines of therapy, including in relapsed and refractory settings."

Enterome recently announced that it will present new data showing EO2463 also has a meaningful impact when tested in combination with standard of care in relapsed and refractory iNHL patients at the International Conference on Malignant Lymphoma (ICML) in Lugano on June 21. Previous findings presented at ASCO (Free ASCO Whitepaper) in 2024 in the relapsed and refractory patient population further suggested the potential to identify individuals most likely to benefit from EO2463 treatment, supported by biomarker analyses.

Lore Gruenbaum, Chief Scientific Officer at LLS, said, "It is important for us to continue to support Enterome, a company working to develop novel therapeutics based on our shared commitment to create better therapies for blood cancers. LLS has invested over $1.8 billion in groundbreaking research since our inception in 1949. Our active partnership with Enterome, through our Therapy Acceleration Program, will continue to advance the clinical development of the OncoMimics family of novel immunotherapeutics for the benefit of blood cancer patients. We are particularly excited to help advance EO2463 which has shown promising signs of efficacy as monotherapy with excellent safety and tolerability in ‘watch-and-wait’ iNHL patients, who currently have no approved treatment options."

EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimics peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that mimic the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2). The unique ability of EO2463 immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes. By ensuring broad target coverage across malignant B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune-resistance mechanisms such as antigen escape.

SIDNEY is an ongoing 12-month open label Phase 1/2 study that aims to assess safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in up to about 55 patients with follicular lymphoma and marginal zone lymphoma including divided into three cohorts: newly diagnosed patients eligible to watch-and-wait (monotherapy); newly diagnosed patients in need of therapy / first line (combo with rituximab); patients with relapsed/refractory disease (combo with R2). In addition to safety, survival, response rates and other measures of efficacy are being collected.

OncoMimics were inspired by the microbial origin of certain autoimmune diseases. The Company uses AI and machine learning to identify microbial proteins that closely mimic the structure, effect or actions of specific cancer antigens (as well as hormones or cytokines). Memory T cells against microbial antigen are created during early development, sometimes leading to autoimmune disorders. In the case of OncoMimics, however, this means that the immune system can mount a rapid, robust and durable immune response that is highly targeted and specific for the OncoMimics and the cancer antigens they closely resemble.

This is possible because, unlike cancer antigens, OncoMimics bypass the biological process, known as thymic deletion, that prevents the immune system from mounting an attack against the "self" proteins (e.g. antigen) on tumor and blood cancer cells. Once activated, the immune system attacks with high specificity and potency the cancer antigens targeted by the OncoMimics, killing the cancer cells that carry them. OncoMimics are synthetic peptides that are easy to manufacture, store, distribute and administer as an off-the-shelf subcutaneous injection. In clinical testing to date they have been shown to be extremely well tolerated, especially compared to other potent immunotherapies.

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.