On November 4, 2021 Targovax ASA (OSE: TRVX), a clinical stage biotechnology company developing immune activators to target hard-to-treat solid tumors, reported its third quarter 2021 results (Press release, Targovax, NOV 4, 2021, View Source [SID1234594409]). Targovax’s CEO will give an online presentation and update on the clinical program to investors, analysts and the press at 10:00 CET today (details below).

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THIRD QUARTER HIGHLIGHTS
Received acceptance of two posters to be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November
Presented poster at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper)
Received European Patent for ONCOS-102 in combination with chemotherapy
Announced Dr Lone Ottesen’s appointment as Chief Development Officer and Ola Melin as Head of Manufacturing
POST-PERIOD HIGHLIGHTS
In October, Dr. Erik Digman Wiklund was appointed as new Chief Executive Officer. Dr. Wiklund has a strong scientific background in cancer research, and intimate knowledge of the company and its technology having served as Chief Business Officer and Chief Financial Officer of Targovax since 2017. Former CEO Øystein Soug will remain with the company following the appointment of Dr. Wiklund. Mr. Soug will act as a special advisor and also serve as interim CFO providing important strategic and management continuum for the company.

KEY FIGURES
Erik Digman Wiklund, CEO commented: "Taking over the leadership of Targovax at a time when we have demonstrated a clear signal of efficacy accompanied by a deep biomarker data package for our lead candidate ONCOS-102, is a truly exciting opportunity. The insights we have gained allow us to select the optimal combination strategy for the next development step, as well as to design innovative and differentiated second generation ONCOS vectors to shape our platform for the future."

Presentation

We invite to a live webcast today at 10.00 CET. You can join the webcast here. It will be possible to ask questions during the presentation.

On November 4, 2021 Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7) (Vivoryon), a clinical stage company focused on discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, reported financial results and the corporate update for the third quarter of 2021, ending September 30, 2021 (Press release, Vivoryon Therapeutics, NOV 4, 2021, View Source [SID1234594408]). The report is available on the Company’s website at www.vivoryon.com/investors-news/financial-information

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"Throughout the third quarter, we made significant progress towards filling the gap of safe, widely available effective disease-modifying therapies in Alzheimer’s disease. Both our newly initiated study VIVA-MIND in the U.S. and our ongoing European study VIVIAD are progressing steadily and we have implemented a number of measures to ensure that the Company is able to deliver on its objectives, including stringent clinical development beyond the currently ongoing studies," said Dr. Ulrich Dauer, CEO of Vivoryon.

Corporate Highlights and R&D Updates

Varoglutamstat

In August 2021, details on the study background and design of Vivoryon’s European Phase 2b study VIVIAD in patients with mild cognitive impairment and mild AD were published in the Journal "Alzheimer’s Research & Therapy" (Vijverberg et al., View Source). The study is enrolling patients as planned despite the ongoing global pandemic. To avoid delays in recruitment and as a reaction to COVID-19-related patient and staff protection policies implemented at German study sites, Vivoryon is in the process of increasing the overall number of study sites, aiming to more than double the originally planned number. VIVIAD remains on track for an interim safety readout in mid-22 and Vivoryon continues to anticipate final data in the second half of 2023.
In September 2021, Vivoryon initiated its U.S. Phase 2a/b VIVA-MIND study for varoglutamstat in patients with early AD. VIVA-MIND is a combined Phase 2a/b study which seeks to enroll 180 patients into the Phase 2a adaptive dose finding part, with an interim futility analysis planned for H1/2023. If predefined criteria are fulfilled, the trial will pass a stage-gate into the Phase 2b part, enrolling an additional 234 patients treated at the selected dose for at least 72 weeks, with a total of 414 patients being treated on stable doses of varoglutamstat for 18 months. The primary endpoint for this study is CDR-SB (clinical dementia rating scale – sum of boxes), an established approvable endpoint measuring a combination of cognitive abilities and activities of daily living. The VIVA-MIND study is sponsored by Vivoryon and the study director is Dr. Howard Feldman, Professor of Neurosciences and Director of the Alzheimer’s Disease Cooperative Study (ADCS) at the University of California San Diego School of Medicine. The study is coordinated by the ADCS, and supported by the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), with a US$15 million grant (NIA award number R01AG061146). The study is ongoing with two sites now approved to screen participants and a group of another seven sites having secured regulatory approval.
Patent Portfolio

In the third quarter of 2021, Vivoryon further expanded its patent portfolio. Year to date (as of October 31, 2021) a total of 16 additional patents have been granted for the Company’s small molecule inhibitors and antibody-based medicines in development to treat AD and other diseases with exceptionally high medical need.

Post-period Events

In October 2021, the Company announced that it has decided to expand its manufacturing capabilities for production of active pharmaceutical ingredient (API) by initiating a second line of manufacturing with an additional partner to ensure sustainable study drug supply with varoglutamstat for the VIVA-MIND U.S. study. This will increase the total number of manufacturing sites for varoglutamstat to three on two different continents, providing supply for VIVA-MIND beyond the ongoing Phase 2a adaptive dose finding part, as well as for potential future studies in other geographies, with the added benefit of increasing flexibility to react to global challenges such as the ongoing pandemic.
Also in October 2021, Vivoryon and its collaboration partners published data providing strong preclinical evidence of treatment with a combination of the Company’s small molecule QPCT/L inhibitor varoglutamstat and its N3pE amyloid-specific antibody PBD-C06 having an additive effect on reducing brain Abeta pathology in transgenic mice. The data, published in the "International Journal of Molecular Sciences" (Hoffmann et al., View Source), support the hypothesis of a potential benefit of a combination therapy designed to simultaneously target two different and independent molecular pathways, namely reducing N3pE amyloid production by QPCT/L inhibition and clearing existing Abeta deposits through anti-N3pE-immunotherapy. This provides a strong rationale for the evaluation of therapies combining varoglutamstat with monoclonal antibodies to treat AD.
Financial Results for Q3 of 2021

In Q3, the Company generated license revenues of EUR 10.8 million from a strategic regional licensing partnership signed with its partner Simcere on June 29, 2021 for Greater China. No revenues were generated in 2020, respectively.

Research and development expenses incurred for the nine months ended September 30, 2021 increased over the corresponding period in 2020 by EUR 3.6 million. This increase was mainly driven by EUR 2.9 million higher expenses for production and Vivoryon’s clinical studies, as well as EUR 0.7 million higher expenses for share-based payments.

General and administrative expenses increased by EUR 1.2 million for the nine months ended September 30, 2021. This increase is largely attributable to EUR 0.3 million higher consulting costs and EUR 0.7 million higher expenses for share based payments. The increase in consulting costs resulted from preparations for a potential future listing on Nasdaq.

Net loss for the nine months ended September 30, 2021 was EUR 7.3 million, compared to EUR 12.2 million for the nine months ended September 30, 2020. The Company held EUR 19.9 million in cash and cash equivalents as of September 30, 2021, compared to EUR 26.3 million as of December 31, 2020.

Financial Guidance

On October 18, 2021, Vivoryon updated its financial guidance to account for costs associated with the expansion of its manufacturing capabilities for production of active pharmaceutical ingredient (API) by initiating a second line of manufacturing with an additional partner to ensure sustainable study drug supply with varoglutamstat for the VIVA-MIND U.S. study. According to current planning and estimates, the Company now expects a cash reach until mid-2022. A detailed update on anticipated working capital requirements and associated potential financing activities as well as resulting timelines will be given in the context of Vivoryon’s regular filings.

Unaudited Condensed Interim Financial Statements

Vivoryon Therapeutics N.V.

Condensed Statements of Operations and Comprehensive Income and Loss

On November 4, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) and Novartis reported that they agreed on a repurchase by Roche of the 53.3 million Roche shares held by Novartis (Press release, Hoffmann-La Roche, NOV 4, 2021, View Source [SID1234594407]). The aggregate transaction value is approx. CHF 19 billion. The price per share is CHF 356.9341. It corresponds to the volume weighted average price of the Roche non-voting equity certificates over the last 20 trading days up to and including 2 November 2021. The Board of Directors of Roche has approved the envisaged repurchase, which will be debt-financed by Roche. All shareholders and holders of non-voting equity certificates of Roche benefit from the earnings accretion resulting from the transaction.

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Christoph Franz, Chairman of the Board of Directors of Roche: "I am convinced that the envisaged transaction is in the best interest of Roche and the holders of Roche equity securities from a strategic and economic perspective. As a result, Roche will be even better positioned strategically in the future to provide life-saving medicines and diagnostics to people around the world."

The transaction does not result in a change of control, as the pool formed by shareholders of the founding families has held the majority of the votes represented at general meetings of Roche previously. The voting power of the family pool will increase to approx. 67.5% upon completion of the transaction without any involvement or participation of the family pool in the transaction. The representatives of the family pool did not participate in the deliberations and the vote of the Board of Directors on this transaction. Based on a request of the family pool, the Swiss Takeover Board has exempted the pool from the obligation to submit a mandatory offer based on the applicable statutory provisions.

The percentage of shares held by the public (so-called "free float") will increase from currently 16.6% to 24.9% with the cancellation of the equity stake held by Novartis. This will allow the shares to be included in the Swiss Performance Index (SPI) and possibly in other indices.

The Extraordinary General Meeting to approve the capital reduction by cancellation of the shares repurchased from Novartis and to approve the interim financial statements prepared for the purpose of this transaction will be held on 26 November 2021. In accordance with the Articles of Association of Roche, the official invitation will be published twice in the Swiss Official Gazette of Commerce (SHAB; View Source!/gazette), for the first time on Friday, 5 November 2021. In addition, the invitation advertisement will be published in the daily and financial press from Monday, 8 November 2021.

Roche confirms the outlook for the full year and expects a mid-single-digit sales growth at constant exchange rates. Core EPS growth at constant exchange rates is targeted to be broadly in line with sales growth. Furthermore, Roche is aiming at increasing the dividend in Swiss francs also for 2021.

On November 4, 2021 Sanofi reported that Six oral and 14 poster presentations will be featured during the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from December 11-14 (Press release, Sanofi, NOV 4, 2021, View Source [SID1234594406]).

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"These upcoming data presentations demonstrate our ongoing commitment to delivering meaningful innovations for patients with significant unmet needs in oncology and hematology," said Dietmar Berger, Global Head of Clinical Development and Chief Medical Officer, Sanofi. "In our efforts to support the transformation of therapeutic landscapes, we look forward to presenting our Phase 3 results on fitusiran’s ability to provide protection from bleeds for people with hemophilia A or B with inhibitors. We’re also pleased to work with GMMG as they present investigational data evaluating Sarclisa in patients with newly diagnosed multiple myeloma, the first Phase 3 trial adding an anti-CD38 monoclonal antibody in combination with bortezomib, lenalidomide and dexamethasone."

Understanding the potential for Sarclisa (isatuximab-irfc) in earlier lines of therapy for multiple myeloma and other blood cancers

New data are from the Phase 3 German-Speaking Myeloma Multicenter Group (GMMG) HD7 study evaluating the effect of isatuximab in combination with bortezomib, lenalidomide and dexamethasone (VRd) on the rate of achieving minimal residual disease (MRD) negativity in transplant-eligible patients with newly diagnosed multiple myeloma (MM) after induction therapy, before transplant. These are the first results from a Phase 3 trial adding an anti-CD38 monoclonal antibody to VRd, a recommended first regimen in transplant-eligible newly diagnosed MM. GMMG-HD7 is also the first trial to evaluate MRD negativity at the end of induction as a co-primary endpoint, along with progression free survival, in transplant-eligible patients with newly diagnosed MM. The results of the study were selected as an oral presentation (abstract #463) and as part of the press program. Sanofi provided financial support to GMMG for this study.

Additionally, data from the Phase 2 ISAKIDS trial evaluating isatuximab in combination with standard salvage chemotherapies in children with relapsed or refractory leukemia in first or second relapse will be shared as an oral presentation (abstract #516).

The uses of Sarclisa in adult patients with newly diagnosed multiple myeloma and children with leukemia are currently under clinical investigation and their safety and efficacy in these settings have not been fully evaluated by any regulatory authority.

Sarclisa is approved in several geographies, in combination with pomalidomide and dexamethasone, for the treatment of certain adult patients with relapsed refractory MM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. This anti-CD38 monoclonal antibody medicine is also approved in several geographies in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory MM who have received one to three prior lines of therapy.

Advancing our innovative approaches to find treatments for people with rare blood disorders

Hemophilia: The results of the ATLAS-003 Phase 3 study evaluating fitusiran prophylaxis in patients with hemophilia A or B with inhibitors dosed with the 80 mg monthly treatment will be presented in the plenary scientific session (abstract #150273).

Additionally, the Phase 1/2 study results for long-term health-related quality of life in patients with hemophilia A, with or without inhibitors, treated with fitusiran prophylaxis will be shared in a poster presentation (abstract #3197).

Fitusiran is a novel, subcutaneous small interference (si)RNA therapy in development for people with hemophilia A or B, with or without inhibitors.

A post hoc analysis from the Phase 1/2 studies looking at the half-life and clearance of efanesoctocog alfa – previously known as BIVV001 – will be shared in a poster presentation (abstract #1035).

Efanesoctocog alfa is an investigational once-weekly factor therapy for people with hemophilia A that may provide high sustained factor activity and near-normal factor levels for the majority of the week. It represents a potential new class of factor VIII therapy. Efanesoctocog alfa is being developed in collaboration with Sobi.

Fitusiran and efanesoctocog alfa are currently under clinical investigation and their safety and efficacy have not been evaluated by any regulatory authority.

Cold Agglutinin Disease (CAD): An oral presentation (abstract #349) shares new data from the CADENZA study, looking at the safety and efficacy of sutimlimab to inhibit C1- activated hemolysis in people with CAD. Additionally, two poster presentations (abstracts #4057 and #2002) provide an overview of the burden of living with CAD, including patient-reported outcome symptom measures. Also, a new analysis from the Phase 3 CARDINAL and CADENZA studies which evaluated sutimlimab in CAD, will report on physical and mental component summary scores and contribution to fatigue in people living with the disease.

Sutimlimab, a first-in-class investigational C1s inhibitor, has the potential to be the first approved treatment for hemolysis in adults with CAD, a serious and chronic autoimmune hemolytic anemia. Sutimlimab is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

Immune Thrombocytopenic Purpura (ITP): An oral presentation on rilzabrutinib, an investigational oral Bruton tyrosine kinase inhibitor (BTKi), reports on updated Phase 1/2 safety and efficacy results for the treatment of ITP (abstract #14) and a poster presentation (abstract #1010) on the design of the Phase 3 LUNA3 study. Rilzabrutinib is a potential first-in-class, oral BTKi in development for immune-mediated diseases. It is also being investigated for the autoimmune condition IgG4-related disease, asthma, atopic dermatitis, chronic spontaneous urticaria and warm autoimmune hemolytic anemia.

Rilzabrutinib is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

Acquired Thrombotic Thrombocytopenic Purpura (aTTP): Two poster presentations will share safety and efficacy results for Cablivi (caplacizumab-yhdp) in aTTP: abstract #2080 will share long-term safety and efficacy from the post-HERCULES study in aTTP; additionally, abstract #1009 will show results from a Phase 2/3 study in Japanese patients with immune-mediated TTP.

Cablivi (caplacizumab-yhdp) is approved in several geographies in combination with plasma exchange and immunosuppression for the treatment of aTTP in adults.

Sickle Cell Disease: Preliminary data from the ongoing Phase 1/2 PRECIZN-1 study evaluating the safety and efficacy of SAR445136, formerly known as BIVV003, for the treatment of patients with severe sickle cell disease will be shared in a poster presentation (abstract #2930). SAR445136, an investigational zinc finger nuclease ex vivo gene-edited cell therapy in development with Sangamo, has the potential to be a one-time treatment for sickle cell disease.

SAR445136 is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

Oncology Abstracts:

Abstract #463: Addition of Isatuximab to Lenalidomide, Bortezomib and Dexamethasone as Induction Therapy for Newly-Diagnosed, Transplant-Eligible Multiple Myeloma: The Phase III GMMG-HD7 Trial​. Oral presentation by GMMG. Sanofi provided financial support for this study.
Abstract #516: Isatuximab in Combination with Chemotherapy in Pediatric Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (ISAKIDS): Interim Analysis​. Oral presentation.
Abstract #4114: Real-World Multiple Myeloma Treatment Patterns by Patient Characteristics and Outcomes in the United States. Poster.
Abstract #2744: A Multi-Center, Phase 1b Study to Assess the Safety, Pharmacokinetics and Efficacy of Subcutaneous Isatuximab Plus Pomalidomide and Dexamethasone, in Patients with Relapsed/Refractory Multiple Myeloma​. Poster.
Abstract #1962: A Matching-Adjusted Indirect Comparison of lsatuximab Plus Carfilzomib and Dexamethasone Versus Daratumumab Plus Lenalidomide and Dexamethasone for Relapsed Multiple Myeloma​. Poster.
Abstract #1671: Isatuximab Rescue for Inadequate Response to Lenalidomide and Dexamethasone in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: Interim Analysis of the Phase II IRIL Study of the Australian Myeloma Research Consortium (AMaRC 18-02). Poster.
Abstract #4362: A Phase 1/2, Open-Label, Multicenter Study of Isatuximab in Combination with Cemiplimab in Patients with Lymphoma. Abstract online only.
Abstract #4769: ITHACA, a Randomized Multicenter Phase 3 Study of Isatuximab in Combination with Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma: Safety Run-In Preliminary Results. Abstract online only.
Abstract #4767: Trial in Progress: A Phase 2 Multi-Center, Open Label Study of Isatuximab Added to Standard CyBorD Induction and Lenalidomide Maintenance Treatments in Newly Diagnosed, Transplant Eligible Multiple Myeloma. Abstract online only.

Rare Blood Disorders Abstracts:

Hemophilia

Abstract #150273: Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI). Plenary scientific session.
Abstract #498: Prophylaxis with rFIXFc Reduces the Frequency and Delays Time to First Spontaneous Bleed Event in Previously Untreated Patients with Hemophilia B: A Post Hoc Analysis of the PUPs B-LONG Trial​. Oral presentation joint with Sobi.
Abstract #3197: Sustained Improvement in Health-Related Quality of Life in Patients with Hemophilia A with or without Inhibitors Treated with Fitusiran Prophylaxis​. Poster.
Abstract #1035: Efanesoctocog Alfa Half-life and Clearance Are Independent of von Willebrand Factor in Severe Hemophilia A: A Post Hoc Analysis from Phase 1/2a Studies​. Poster joint with Sobi.
Abstract #3031: A Retrospective Observational Descriptive Study on the Effectiveness and Usage of Emicizumab and Antihemophilic Factor (recombinant), Fc Fusion Protein in Patients with Hemophilia A in the U.S​. Poster.

Cold Agglutinin Disease

Abstract #349: Inhibition of Complement C1s by Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Efficacy and Safety Results from the Randomized, Placebo-Controlled Phase 3 CADENZA Study. Oral presentation.
Abstract #4057: Development of a Cold Agglutinin Disease-Specific Patient-Reported Outcome Symptom Measure. Poster.
Abstract #2002: Clinically Important Change in SF-12v2 Physical (PCS) and Mental (MCS) Component Summary Scores for Patients with Cold Agglutinin Disease: An Analysis Using the Phase 3 CARDINAL and CADENZA Studies. Poster.

Immune Thrombocytopenic Purpura

Abstract #14: Updated Phase I/II Safety and Efficacy Results for Oral Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed/Refractory Immune Thrombocytopenia​. Oral presentation.
Abstract #1010: LUNA3 Phase III Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Oral BTK Inhibitor Rilzabrutinib in Adults and Adolescents with Persistent or Chronic Immune Thrombocytopenia​. Poster.
Acquired Thrombotic Thrombocytopenic Purpura

Abstract #2080: Long-Term Safety and Efficacy of Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura (aTTP): The Post-HERCULES Study. Poster.
Abstract #1009: The Efficacy and Safety of Caplacizumab in Japanese Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP): An Open-Label, Phase 2/3 Study. Poster.
Sickle Cell Disease

Abstract #2930: Preliminary Safety and Efficacy Results from PRECIZN-1: An Ongoing Phase 1/2 Study on Zinc Finger Nuclease-Modified Autologous CD34+ HSPCs for Sickle Cell Disease (SCD). Poster.
Abstract #1860: Quantitative Systems Pharmacology Model of Sickle Cell Disease and Response to Gene Editing Therapy to Support Clinical Development of SAR445136 (BIVV003)​. Poster.

On November 4, 2021 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel irreversible small molecules to treat and improve the lives of patients with genetically defined cancers, reported that an abstract containing preclinical data for BMF-219 has been published in Blood, the journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Biomea Fusion, NOV 4, 2021, View Source [SID1234594405]).

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The study, as published in Blood, analyzed how Biomea’s irreversible menin inhibitor, BMF-219, is impacting acute myeloid leukemia cells against the background of transcription factors in the GEO dataset. Menin is involved in many protein-protein interactions as part of a larger complex, with Menin and MLL/KMT2A being an example of one of those interactions. Here we investigated how ‘219 disrupts menin globally (selective disruption of global menin co-factors in addition to KMT2A).

Figure 1: Menin and various co-factors

A photo accompanying this announcement is available at View Source

The study demonstrates further the ability of BMF-219 to modulate MYC expression in leukemia cells, offering the foundation for exploring its activity in DLBCL cells. Transcription factor (TF) activity inference was calculated by analysis of TF-binding sites established by chromatin immunoprecipitation sequencing (ChIP-seq) GEO datasets that overlap with BMF-219 mediated differentially expressed genes in MOLM-13 cells using a published statistical framework and algorithm. This analysis revealed MYC, and its co-factor MAX, as top TFs regulating this subset of differentially expressed genes by BMF-219, as TF activity inference was highly enriched for both proteins. Established menin co-factors (KMT2A, JUND) also emerged as top candidates in this dataset. These results strongly point toward altered MYC-activity mediated by BMF-219 in leukemia cells, prompting additional exploration in MYC-dependent lymphoid malignancies.

Figure 2: Transcription factor (TF) activity inference using ChIP-seq of differentially expressed genes in MOLM-13 cells incubated with 500 nM BMF-219 at 24 hours. Each bar represents a study in the GEO repository using the specified TF antibody. TFs with more than one bar represent multiple study sets in GEO that overlap with BMF-219 mediated differentially expressed genes. MYC and MAX are top TFs regulating this subset of differentially expressed genes (p=10-49.5). Established menin co-factors (KMT2A, JUND) also emerged as top candidates in this dataset.

A photo accompanying this announcement is available at View Source

Using these results as the basis for further investigation, we explored BMF-219 and menin reversible inhibitors’ impact on cell viability in two different DLBCL double hit lymphoma (DHL) cell lines (DB and Toledo). Single-agent BMF-219 reduced >90% of cell viability in DB and Toledo cells, at 1.0μM and 0.36 μM, respectively. The IC50 values of BMF-219 were calculated near 0.3 mM for both DB and Toledo cells; however, the two reversible menin inhibitors tested were significantly less effective. One of the reversible inhibitors exhibited IC50 values at multi-fold higher drug concentrations than BMF-219 in both cell lines tested and the other reversible compound tested did not show sensitivity to either cell line.

"With this study, we gained valuable understanding and expanded our knowledge into the mechanism of action of our irreversible menin inhibitor, BMF-219. Besides its targeted selectivity profile, we also recognize the broad impact BMF-219 has on the complexes surrounding menin," said Alex Cacovean, M.D., Biomea Fusion’s Executive Medical Director. "At low dosage levels, by targeting menin, we were able to inhibit MYC gene expression and demonstrated potent cell killing in two very aggressive cell lines, representative of underserved DLBCL subpopulations. We are very excited about these preclinical findings and we are hopeful to now clinically validate the effects of our irreversible menin inhibitor in MYC-positive, double expressor, and double hit DLBCL patients."

Abstract Details

Title: Novel Irreversible Menin Inhibitor, BMF-219, Shows Potent Single Agent Activity in Clinically Relevant DLBCL Cells
Abstract Number: 148045

About Diffuse Large B Cell Lymphoma (DLBCL)

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of Non-Hodgkin Lymphoma. DLBCL starts in white blood cells called lymphocytes and grows in lymph nodes. Every year, there are ~18,000 people in the United States that are diagnosed with DLBCL. Following initial treatment with standard chemotherapy, ~70% of people have a complete response and ~50% of patients are cured. For patients with relapsed or refractory DLBCL, median overall survival is between 6-7 months. Double Hit Lymphomas (DHL) and Double Expressor Lymphomas (DEL) are high grade B cell lymphomas (HGBLs) that have high MYC and BCL2 dependency.

About BMF-219

BMF-219 is an irreversibly binding inhibitor of menin, a protein that is known to play an essential role in oncogenic signaling in genetically defined leukemias. Preclinically, BMF-219 has demonstrated robust downregulation of key leukemogenic genes in addition to menin itself (via MEN1) in well-established MLLr AML cell lines. Additionally, BMF-219 has shown efficacy in multiple in vivo and in vitro models of acute leukemias. BMF-219 will be evaluated in a first-in-human trial in patients with relapsed or refractory acute leukemia with MLL/KMT2A gene rearrangement or NPM1 mutation.