On December 11, 2021 Imago BioSciences, Inc. ("Imago") (Nasdaq: IMGO), a clinical stage biopharmaceutical company discovering new medicines for the treatment of myeloproliferative neoplasms (MPNs), today presented positive data from its ongoing global Phase 2 clinical study evaluating bomedemstat in patients with advanced myelofibrosis (MF) (Press release, Imago BioSciences, DEC 11, 2021, View Source [SID1234596813]). The data were presented in an oral session during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 11-14, 2021. Previously, a Phase 2 data set with a cut-off date of May 17, 2021 was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress.

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Updated Highlights (as of November 1, 2021 cutoff):

Of the evaluable patients at 24 weeks:
74% (17/23) showed a decrease in Total Symptom Score (TSS).
26% (6/23) showed a ≥50% decrease in TSS.
75% (30/40) showed spleen volume reductions.
81% (103/127) of mutant allele frequencies (MAFs) were either stable (45%) or reduced (36%), including driver and high molecular risk (HMR) mutations such as ASXL1.
89% (32/36) of patients who were transfusion-independent at baseline had stable or improved hemoglobin at 12 weeks.
No new mutations or transformation to acute myeloid leukemia (AML) in more than 600 days of follow-up in patients with high risk of progression.
"Today’s ASH (Free ASH Whitepaper) 2021 data further demonstrates the potential of bomedemstat as a unique and differentiated treatment option for patients living with advanced myelofibrosis," said Wan-Jen Hong, M.D., CMO, Imago BioSciences. "We were gratified to reach full enrollment in our myelofibrosis trial earlier this year and remain pleased with the safety and tolerability profile observed to date. Looking ahead, we anticipate continued momentum in this program through an investigator-sponsored trial evaluating bomedemstat in combination with ruxolitinib in MF patients who are either treatment naïve or respond sub-optimally to ruxolitinib treatment."

Safety & Tolerability

Bomedemstat was generally well-tolerated to date in patients with myelofibrosis.
The most common non-hematologic AE related to bomedemstat was dysgeusia (altered taste), which occurred in 27 patients (30%).
"Bomedemstat continues to show strong potential as a monotherapy that may offer distinct clinical benefits for patients living with advanced myelofibrosis," said Hugh Y. Rienhoff, Jr., M.D., CEO, Imago BioSciences. "A large majority of the patients enrolled in this trial saw improvements in symptom scores, spleen volumes and occurrence of anemia. Altogether, these data show that bomedemstat may have a significant impact on this progressive and often debilitating disease."

Details on Imago’s ASH (Free ASH Whitepaper) Presentation

Oral Presentation Title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) for the Treatment of Advanced Myelofibrosis
Session: Myeloproliferative Syndromes: Clinical and Epidemiological: Novel Therapies for MPNs and JAK inhibitors for Myelofibrosis
Presenter: Harinder Gill, M.D., study investigator and presenter of the data, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong
Date and Time: December 11, 2021, at 12:00 PM ET

For further details, please see the ASH (Free ASH Whitepaper) 2021 abstract and presentation on the Imago website here.

About Imago’s Phase 2 Advanced Myelofibrosis Program

Myelofibrosis (MF) is a progressive cancer in which the bone marrow is gradually replaced by fibrous, scar-like tissue. There is a significant unmet need for a disease-modifying therapy. The need is greatest in patients with MF whose disease is not adequately managed with current JAK inhibitors, the current standard of care.

This Phase 2b multi-center, open-label study is designed to assess the safety, efficacy, pharmacodynamics, and spleen volume reduction of bomedemstat, an oral inhibitor of the lysine-specific demethylase 1 (LSD1). Eligible patients aged 18 or over with MF who are refractory or resistant to, intolerant of, are inadequately controlled by or ineligible for approved therapies were considered for the study. Exploratory assessments include symptom reduction, changes in cytokine profiles, changes in the frequency of mutant alleles and bone marrow fibrosis. The trial is being conducted in the United States, United Kingdom, European Union and Hong Kong. This ongoing 24-week study completed enrollment in May 2021 for a total of 89 patients.

On December 11, 2021 MorphoSys US Inc., a fully owned subsidiary of MorphoSys AG (FSE: MOR; NASDAQ: MOR), and Incyte (NASDAQ:INCY) reported additional real-world evidence results from the RE-MIND2 study comparing tafasitamab (Monjuvi) in combination with lenalidomide against the most frequently used treatments in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Incyte, DEC 11, 2021, View Source [SID1234596812]). These treatments include polatuzumab vedotin plus bendamustine and rituximab (Pola-BR), rituximab plus lenalidomide (R2), and CD19 chimeric antigen receptor T-cell (CAR-T) therapies. The data, which builds on the primary analysis presented at the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO 2021), will be presented as an oral presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2021), held December 11-14, 2021 in Atlanta, Georgia and virtually.

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"In this retrospective cohort analysis, a statistically significant OS difference was observed, favoring tafasitamab plus lenalidomide over pola-BR and R2 in patients with relapsed or refractory DLBCL who are ineligible for transplant – a traditionally difficult-to-treat population," said Grzegorz Nowakowski, M.D., Professor of Medicine and Oncology at the Mayo Clinic, and lead investigator for the RE-MIND2 study*. "I am encouraged by the OS difference favoring tafasitamab plus lenalidomide and the comparable OS between tafasitamab and lenalidomide and CAR-T, specifically the potential prolonged survival benefit the tafasitamab plus lenalidomide combination may offer my patients."

Findings from the RE-MIND2 study presented at ASH (Free ASH Whitepaper) 2021 indicated that tafasitamab plus lenalidomide resulted in statistically significant differences across several endpoints. Specifically, results showed:

The primary endpoint, overall survival (OS), was met with significant improvement observed for tafasitamab plus lenalidomide at 20.1 months compared to Pola-BR at 7.2 months (p=0.038), and 24.6 months for tafasitamab plus lenalidomide compared to 7.4 months for R2 (p=0.014).
A comparable median OS benefit was observed with tafasitamab plus lenalidomide at 22.5 months compared to CAR-T at 15 months without statistical significance.
Objective response rate (ORR), a key secondary endpoint, was observed with statistical significance for tafasitamab plus lenalidomide at 63.6% versus R2 at 30.3% (p=0.013).
Tafasitamab plus lenalidomide also achieved significantly higher complete response rate (CR), a key secondary endpoint, at 39.4% versus 15.2% for R2 (p=0.0514).
While safety endpoints were not included in this study, the most common adverse events (AEs) associated with tafasitamab plus lenalidomide are feeling tired or weak, diarrhea, cough, fever, swelling of lower legs or hands, respiratory tract infection and decreased appetite.
Of 3,454 patients enrolled from 200 sites, 106, 106 and 149 patients were treated with pol-BR, R2 and CAR-T, respectively. For the comparative analysis, matched patient pairs were created using 1:1 nearest neighbor matching with a caliper. Matched pairs consisted of: tafasitamab + len vs pol-BR, n=24 pairs; vs R2, n=33; and vs CAR-T, n=37 pairs.

"The RE-MIND 2 Study is an example of our continued commitment to generating practice relevant real-world evidence which, in general, more realistically captures the clinical heterogeneity in cancer and allows us expanded opportunities to dynamically assess the patient experience. These data indicate that tafasitamab plus lenalidomide is a meaningful option for patients and has the potential to become a future backbone therapy in DLBCL," said Nuwan Kurukulasuriya, Ph.D., Senior Vice President, Global Head of Medical Affairs, MorphoSys.

"We are pleased to see the survival benefit for patients with relapsed or refractory DLBCL in the data from the RE-MIND2 study," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "As we continue to establish tafasitamab in combination with lenalidomide as the standard of care in second-line treatment for DLBCL, we look forward to exploring the body of clinical evidence and bringing this novel treatment to patients with DLBCL and potentially even to other indications."

Presentations are available on the ASH (Free ASH Whitepaper) website at View Source; #183 (oral presentation).

In July 2020, the U.S. Food and Drug Administration (FDA) approved Monjuvi (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for ASCT. This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The U.S. approval is based on an efficacy subgroup of 71 patients confirmed by central lab. The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy.

About Diffuse Large B-cell Lymphoma (DLBCL)

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide1, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about 40% of patients not responding to initial therapy or relapsing thereafter2, leading to a high medical need for new, effective therapies3, especially for patients who are not eligible for an autologous stem cell transplant in this setting.

About RE-MIND2

The RE-MIND2 study is an observational, retrospective cohort study (NCT04697160) that compares outcomes with those from the L-MIND study for autologous stem cell transplant (ASCT)-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), who are treated with therapies recommended by the National Comprehensive Cancer Network/European Society for Medical Oncology (NCCN/ESMO). The study utilized real-world data to generate external comparators for patients in the L-MIND trial. The primary analysis of the study compared patient outcomes from L-MIND with matched patient populations treated with gemcitabine-oxaliplatin plus rituximab (R-GemOx), bendamustine and rituximab (BR) and pooled systemic NCCN/ESMO recommended therapies. The additional analysis evaluated tafasitamab in combination with lenalidomide versus Pola-BR, R2 and CAR-T therapies. Patients enrolled in the study were aged 18 years or older with histologically confirmed DLBCL and had received two or more systemic therapies for DLBCL, including one or more anti-CD20 therapy. The study’s primary endpoint is overall survival (OS). Secondary outcome measures include overall response rate (ORR), complete response rate (CRR), duration of response (DoR), event-free survival (EFS), progression-free survival (PFS), time to next treatment (TTNT), treatment discontinuation rate due to adverse events and duration of treatment exposure.

For more information about RE-MIND2, visit View Source

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Monjuvi and Minjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S., and marketed by Incyte under the brand name Minjuvi in the EU.

XmAb is a registered trademark of Xencor, Inc.

Important Safety Information

What are the possible side effects of MONJUVI?

MONJUVI may cause serious side effects, including:

Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, rash, flushing, headache, or shortness of breath during an infusion of MONJUVI.
Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or any bruising or bleeding.
Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or develop any signs and symptoms of an infection.
The most common side effects of MONJUVI include:

Feeling tired or weak
Diarrhea
Cough
Fever
Swelling of lower legs or hands
Respiratory tract infection
Decreased appetite
These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

Have an active infection or have had one recently.
Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.
You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.
Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.
You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see the full Prescribing Information for Monjuvi, including Patient Information, for additional Important Safety Information.

On December 11, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported an oral presentation highlighting updated data from the Phase 2 ESSENTIAL study, an investigator-sponsored study evaluating single-agent selinexor, a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in patients with myelofibrosis (MF) previously treated with JAK inhibition (Press release, Karyopharm, DEC 11, 2021, View Source [SID1234596811]). These updated results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting and Exposition taking place in Atlanta, GA on December 11-14, 2021.

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"The results presented at ASH (Free ASH Whitepaper) this year demonstrate that once weekly single-agent oral selinexor resulted in an impressive spleen volume reduction rates in myelofibrosis patients who received at least 24 weeks of treatment, with 40% and 60% of those patients achieving a response, defined as spleen volume reduction (SVR) of at least 35% and 25%, respectively. The durable responses and well-tolerated safety profile highlight selinexor’s potential in patients with JAK-refractory myelofibrosis," said Srinivas Tantravahi, MBBS, MRCP, University of Utah Hospital and principal investigator of the Phase 2 ESSENTIAL study. "With JAK inhibitors being the only class of drugs approved for this disease and with less than half of patients responding, there remains a high unmet need for patients who either progress following treatment with a JAK inhibitor or are intolerant."

"Following the encouraging data from the Phase 2 ESSENTIAL trial, we recently dosed the first patient in Karyopharm’s new Phase 2 study evaluating single-agent selinexor versus physician’s choice in patients with previously treated myelofibrosis," said Sharon Shacham, PhD, MBA, Co-Founder and Chief Scientific Officer of Karyopharm. "As part of our strategic imperatives and pipeline priorities, we remain focused on diseases with the highest unmet needs and greatest potential to make an impact in patient outcomes."

Results from the Phase 2 ESSENTIAL Study Evaluating Single-Agent Selinexor in Patients with MF Refractory or Intolerant to JAK Inhibitors

The results were based on the open label, prospective, investigator-initiated single center ESSENTIAL study in adult patients with primary or secondary MF with resistance or intolerance to JAK inhibitor therapy (NCT03627403). Selinexor was administered orally at a dose of 80mg or 60mg once weekly to 12 patients. The primary endpoint of the study is to assess the efficacy of selinexor on SVR. Median duration of prior JAK inhibitor therapy was 22 months (range 0.5 to 96 months) and 92% (11 of 12) patients had MF refractory to ruxolitinib.

As of the data cutoff, the median duration of treatment was 11 months (range 2.8 to 28.8 months). Of the ten patients who were on treatment for at least 24 weeks, four (40%) patients achieved SVR of ≥35% and six (60%) patients achieved SVR of ≥25%. Of the five patients who were transfusion dependent at screening, two (40%) achieved transfusion independence. Of the three patients with hemoglobin <10g/dL at screening, improvement was observed in two (67%) patients. Reduction in marrow reticulin fibrosis from MF grade 3 to MF grade 1 was observed in a patient who had an assessment at week 72 demonstrating disease modification potential with longer treatment. While median overall survival was not yet reached, the two-year survival probability was assessed to be 91.7%. This compares favorably with a historical survival of 13-14 months in this population.

The most common grade ≥3 treatment emergent adverse events were anemia (33%) and fatigue (33%). These were manageable with treatment interruption and dose reduction, except in one patient who discontinued treatment.

Details for the ASH (Free ASH Whitepaper) 2021 presentation are as follows:

Title: A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor in Patients with Myelofibrosis Refractory or Intolerant to JAK Inhibitors
Presenter: Srinivas Tantravahi, University of Utah
Abstract #: 143
Session Type: Oral Presentation
Session: Myeloproliferative Syndromes: Clinical and Epidemiological: Non-JAK Inhibitor Therapies for Myelofibrosis

A PDF copy of the presentation is available here.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

On December 11, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported new results for higher dose level cohorts of its investigational REGN5458 (BCMAxCD3) bispecific antibody, which were presented in an oral session at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, GA (Press release, Regeneron, DEC 11, 2021, View Source [SID1234596810]). The new results from the Phase 1 portion of the Phase 1/2 trial in patients with relapsed/refractory multiple myeloma found a 51% overall response rate (ORR) across all dose groups, rising to 75% in patients who received higher doses of REGN5458 (200-800 mg).

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"Patients with multiple myeloma often face a long and challenging journey, with most becoming refractory to multiple lines of therapy over time," said Jeffrey Zonder, M.D., Professor of Oncology at the Karmanos Cancer Institute, MI, and a trial investigator. "Today’s REGN5458 data show promising response rates, particularly at the higher dose levels, in patients with a high disease burden and highly refractory disease who otherwise would have very limited options available."

REGN5458 is a bispecific antibody designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T-cells in order to bridge them together and activate T-cells to kill the cancer cells. It is currently being assessed in the potentially registrational Phase 2 portion of the trial, which is expected to complete recruitment in 2022.

In results presented at ASH (Free ASH Whitepaper) today, 73 patients were treated with REGN5458 doses ranging from 3-800 mg for up to 21 months at the time of data cutoff. Patients had received a median of 5 prior lines of therapy, with 38% (n=28) being penta-refractory and 90% (n=66) being refractory to the last line of therapy.

The ORR was 75% at the highest dose levels (200-800 mg, n=18/24), and 51% among all enrolled patients (n=37/73). Most responses occurred within the first month of treatment and deepened over time. Among responders across all dose groups:

86% (n=32/37) achieved a very good partial response (VGPR) or better.
43% (n=16/37) achieved a complete response (CR), with 40% of evaluable CR patients (n=4/10) being minimal residual disease (MRD) negative.
8 months from the time of response, there was a 90% probability of being event-free (95% CI: 73%, 97%), defined by the absence of disease progression or death. The estimated median duration of response had not yet been reached at the time of data cutoff.
Responses occurred rapidly, usually within the first month of treatment, and continue to deepen with longer treatment; the higher dose groups currently have substantially shorter follow up.
The safety profile was generally consistent across all dose levels. Cytokine release syndrome (CRS) was reported in 38% of patients (n=28), the majority of which were Grade 1 (n=25), with no cases >Grade 3. The other most common treatment-emergent adverse events (TEAEs) were fatigue (n=33), pyrexia (n=26), nausea (n=24) and anemia (n=23). The most common >Grade 3 TEAEs were anemia (n=17), neutropenia (n=16), lymphopenia (n=14), thrombocytopenia (n=10) and pneumonia (n=9). There were 5 deaths in the trial, all due to infection; none were considered related to the underlying disease by investigators.

"In multiple myeloma, the highest treatment response rates are typically seen earlier in the course of the disease, using multi-drug regimens. It is very encouraging that we observed a 75% response rate with higher doses of REGN5458 monotherapy in patients with more advanced disease," said L. Andres Sirulnik, M.D., Ph.D., Senior Vice President, Clinical Development, Hematology at Regeneron. "This adds to the growing body of encouraging data across our investigational CD3 bispecifics, supporting the continued development of this class across a diverse range of blood cancers."

REGN5458 is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.

Investor Webcast Information
Regeneron will host a conference call and simultaneous webcast to share updates on the company’s hematology portfolio on Monday, December 13 at 4:30 PM ET. To access this call, dial (888) 660-6127 (U.S.) or (973) 890-8355 (International); conference ID 2668896. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

About the Dose-escalation Trial
The open-label Phase 1/2 dose-escalation trial is investigating REGN5458 (BCMAxCD3) in patients with relapsed/refractory multiple myeloma who had received at least three prior lines of therapy or were double refractory. All patients had received prior treatment with proteasome inhibitors, immunomodulatory drugs and CD38 antibody treatments.

The Phase 1 portion of the trial is primarily assessing safety, tolerability and dose-limiting toxicities of REGN5458, with efficacy as secondary endpoints. The Phase 2 portion will further assess REGN5458 anti-tumor activity and safety. If you are interested in learning more about this trial, please contact us ([email protected], +1 844 734 6643), or visit our clinical trial website.

About Multiple Myeloma
Multiple myeloma is the second most common blood cancer with approximately 30,192 and 168,765 new diagnoses in the U.S. and the world, respectively, in 2020. It is characterized by the proliferation of cancerous plasma cells (multiple myeloma cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Multiple myeloma is not curable despite treatment advances, and while current treatments are able to slow the progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies. In addition, patients are at increased risk of frequent infections, bone problems, reduced kidney function and anemia.

About Regeneron in Hematology
At Regeneron, we’re translating more than 3 decades of biology expertise with our proprietary VelociSuite technologies to develop potentially paradigm-changing medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being assessed both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing using CRISPR and gene-knockout technologies, as well as investigational RNA-approaches that are being investigated for their ability to deplete abnormal proteins or block disease-causing cellular signaling.

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About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved or authorized fully human monoclonal antibodies currently available. This includes Dupixent (dupilumab), REGEN-COV (casirivimab and imdevimab), Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn).

On December 11, 2021 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biotechnology company employing its pioneering TALEN gene-editing platform to develop innovative therapeutics for the treatment of serious diseases, reorted that preliminary results from the BALLI-01 Phase 1 study of UCART22, its allogeneic CAR-T cell therapy candidate targeting CD22, in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), and preclinical data on TALGlobin01, its autologous cell therapy product candidate for homozygous SCD patients (HbSS) at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, Georgia (Press release, Cellectis, DEC 11, 2021, View Source [SID1234596809]).

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"We are excited by the encouraging preliminary results obtained from patients administered UCART22 after fludarabine, cyclophosphamide and alemtuzumab (FCA) lymphodepletion in the BALLI-01 study. The addition of alemtuzumab to fludarabine and cyclophosphamide (FC) was demonstrated to be safe, improve host-lymphocyte suppression, and promote UCART22 expansion, which was associated with anti-leukemic activity," said Carrie Brownstein, MD, Chief Medical Officer. "We believe these initial data support our mission to develop UCART22 for patients with r/r B-ALL, who remain in dire need of additional treatment options, particularly those who have failed CD19 therapy."

BALLI-01 investigating UCART22 product candidate in R/R B-ALL

BALLI-01, a phase 1 open-label dose-escalation study, is designed to assess the safety, maximum tolerated dose (MTD), and preliminary anti-leukemia activity of UCART22 in patients with r/r B-ALL. Additional endpoints include characterization of the expansion, trafficking, and persistence of UCART22 cells.

The poster presentation includes preliminary data from patients who received UCART22 at dose level 2 (DL2) and intermediate dose level 2 (DL2i) after lymphodepletion with FCA. Alemtuzumab was added to FC to deepen and sustain host lymphocyte suppression and thereby promote UCART22 expansion and persistence.

As of the clinical cut-off date of October 1, 2021, 12 patients received lymphodepletion; 11 were administered UCART22, of which 6 received UCART22 and FCA. Enrolled patients were predominantly male [n=7], young (median age 30 [range 20-61]), and most had recurrent genetic abnormalities including the CRFL2 (cytokine receptor-like factor 2) rearrangement. Additionally, enrolled patients were heavily pretreated with a median of 3 prior lines of therapy [range 2-6]. Three-fourths of patients had received prior blinatumomab, approximately half had received prior inotuzumab, and 3 had received prior CD19 autologous CAR-T therapy.

Safety Data
The FCA lymphodepletion regimen was well tolerated, and most treatment-emergent adverse events (TEAEs) were mild to moderate in intensity and manageable. Importantly, no patients experienced protocol-defined dose limiting toxicities (DLTs), immune effector cell-associated neurotoxicity syndrome (ICANS), nor UCART22-related severe (grade ≥3) TEAEs. Three patients experienced mild to moderate cytokine release syndrome (CRS), and one patient reported grade II GvHD with skin involvement only, that required hospitalization.

Activity Data
Encouraging anti-leukemic activity was observed in two (2/6) patients in the FCA cohorts. Both patients, one at DL2 and one at DL2i, achieved blast reductions to < 5% (0.4% and 0%, respectively) by day 28, accompanied by measurable UCART22 expansion and changes in relevant inflammatory cytokines.

Overall, UCART22 after FCA lymphodepletion regimen demonstrated promising signs of anti-leukemic activity at DL2 and DL2i, without unexpected or significant treatment-related toxicity. The addition of alemtuzumab to the FC lymphodepletion regimen was safe and promoted sustained host T-cell suppression and expansion of UCART22. These data are encouraging and support the further development of UCART22 for patients with r/r B- ALL. BALLI-01 is currently enrolling patients at dose level 3 with FCA lymphodepletion.

TALGlobin01; an autologous ex vivo TALEN-edited hematopoietic stem and progenitor cell gene therapy for the treatment of Sickle Cell Disease

Initial pre-clinical data from Cellectis’ .HEAL platform’s product candidate, TALGlobin01 demonstrates that TALEN is specific and efficient in correcting the mutated beta-globin gene, the underlying cause of sickle cell disease.

The data, presented in a poster, demonstrate that TALEN-based engineering could be used to correct the beta-globin gene mutation in HbSS patient-derived hematopoietic stem and progenitor cells. The data show up to 70% of HBB allelic correction, with only 9% of HBB biallelic inactivation and a low level of TALEN off-target cleavage. Genetic correction of HBB translates into high level of hemoglobin A expression (up to 47% HbA detected among total hemoglobin) and reversion of the sickling phenotype in differentiated red blood cells. Preclinical data show the capacity of TALGlobin01 edited cells to engraft in vivo using an NSG mouse model.

Collectively, the preclinical data demonstrate high efficiency and safety of TALEN treatment in HbSS patient-derived hematopoietic stem and progenitor cells.

A copy of each poster presentation is available on Cellectis’ website, linked here.

About UCART22

UCART22 is an allogeneic T-cell product manufactured from healthy donor cells. T-cells are transduced using a lentiviral vector to express the anti-CD22 chimeric antigen receptor (CAR) and are genetically modified using TALEN gene-editing technology to disrupt the T-cell receptor alpha constant (TRAC) gene to minimize risk of graft-vs-host disease (GvHD) and the CD52 gene to eliminate sensitivity to anti-CD52–directed agents used in lymphodepletion regimens. UCART22 is being developed for the treatment of R/R B-cell ALL.

About TALGlobin01

TALGlobin01, is an autologous ex vivo TALEN-edited CD34+ HSC gene therapy for the treatment of SCD. TALGlobin01 is developed using both TALEN technology to induce a double strand DNA break in the SCD-causing hemoglobin subunit beta (HBB) gene and adeno-associated virus (AAV) particles containing a DNA repair template designed to correct the faulty HBB gene via endogenous homology directed repair.