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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

For more information, visit View Source

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

On December 11, 2021 Ichnos Sciences Inc., a global biotechnology company developing innovative biologics in oncology, reported that preclinical data that support the potential for ISB 1442, a first-in-class 2+1 biparatopic bispecific antibody that targets both CD38 and CD47, as a treatment for relapsed/refractory multiple myeloma and other CD38+ hematological malignancies (Press release, Ichnos Sciences, DEC 11, 2021, View Source [SID1234596808]). The data were presented today by Stefano Sammicheli, Ph.D., Director of Innate Cell Engagers, during an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ISB 1442 includes three arms in a 2+1 biparatopic BEAT 2.0 bispecific[1] format:

Two proprietary high-affinity anti-CD38 binding arms, each targeting different CD38 epitopes, neither of which competes functionally with daratumumab, drive the binding of this molecule to CD38 expressing tumor cells.
A third, lower affinity arm masks CD47 and disrupts binding to SIRPα on macrophages, blocking the "do not eat me signal."
Engineering of the fragment crystallizable (Fc) region enhances antibody dependent cell phagocytosis (ADCP), antibody dependent cell cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC).
Ichnos’ proprietary BEAT 2.0 platform is among the most innovative multispecific platforms: it mimics the natural full length antibody format, the BEAT interface enables high yield for heavy chain pairing, and light chains are assembled via common light chain Fab technique.
The data presented today demonstrate the potency and anti-tumor activity of ISB 1442 in multiple in vitro and in vivo tumor models relative to daratumumab and magrolimab. Specifically, the results show that:

ISB 1442 induces comparable blockade of CD47/SIRPα interactions to the clinical benchmark magrolimab, an antibody that targets CD47.
ISB 1442 enables a significant increase in phagocytosis in CD38 low tumor cells relative to that of daratumumab, an antibody that targets CD38.
ISB 1442 shows higher ADCC relative to daratumumab.
ISB 1442 improved tumor growth inhibition in an in vivo preclinical model compared to daratumumab.
"We are excited to present data on Ichnos’ first-in-class biparatopic CD38 x CD47 bispecific antibody at ASH (Free ASH Whitepaper)," said Mario Perro, Ph.D., Vice President Oncology, Interim Head of Discovery at Ichnos. "ISB 1442 has demonstrated high potency in multiple in vitro tumor models, including one that assessed multiple antibody-dependent mechanisms of actions simultaneously, and higher tumor growth inhibition in vivo. We believe that this asset has the potential to effectively treat patients with multiple myeloma who have relapsed or are refractory to daratumumab as well as other CD38 expressing hematological malignancies."

"Today’s presentation represents another step forward as Ichnos works to bring this novel multispecific approach that co-targets CD38 and CD47 to patients with hematologic malignancies," said Cyril Konto, M.D., President and Chief Executive Officer of Ichnos. "With its unique design and mechanisms of action, data suggest that ISB 1442 may enhance anti-tumor activity relative to approved anti-CD38 targeted therapies by overcoming primary and acquired tumor mechanisms of resistance. We look forward to submitting the IND to FDA in early 2022 and initiating our first-in-human clinical study in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia and T-cell acute lymphoblastic leukemia in the middle of 2022."

The video presentation is available to registered meeting attendees on the ASH (Free ASH Whitepaper) platform. Additional details are also included in the abstract.

Ichnos continues to advance its pipeline of agents based on the proprietary BEAT technology platform. Using this platform, Ichnos is exploring the full design space for treating cancer and engineering multispecific antibodies capable of simultaneously engaging tumor and immune cells.

On December 11, 2021 Incyte (Nasdaq:INCY) reported data from three ongoing Phase 2 studies evaluating parsaclisib, an investigational novel potent, highly selective, next-generation oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), for the treatment of patients with relapsed or refractory follicular lymphoma (FL) (CITADEL-203), marginal zone lymphoma (MZL) (CITADEL-204) and mantle cell lymphoma (MCL) (CITADEL-205) (Press release, Incyte, DEC 11, 2021, View Source [SID1234596807]). These data were accepted as oral presentations 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The primary endpoint for the CITADEL-203, -204 and -205 studies is objective response rate (ORR). Key secondary endpoints include complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and tolerability. All radiology-based endpoints are based on independent review committee (IRC) assessment.

Building on previous findings presented at ASH (Free ASH Whitepaper) 2020, these updated data from the primary analysis continue to show treatment with parsaclisib resulted in a rapid and durable response with an acceptable safety profile, and supported the New Drug Application (NDA) for parsaclisib, recently accepted by the U.S. Food and Drug Administration (FDA).

Key results from the CITADEL studies include:

ORR (95% CI), %

CRR (95% CI), months

mDOR (95% CI), months

mPFS (95% CI), months

mOS (95% CI), months

CITADEL-203: R/R Follicular Lymphoma

DG (N=103)

77.7 (68.4–85.3)

19.4 (12.3-28.4)

14.7 (10.4-NE)

15.8 (11.0-NE)

NR (NE-NE)

All (N=126)

75.4 (66.9-82.6)

18.3 (11.9-26.1)

14.7 (12.0-20.3)

14.0 (11.3-19.6)

NR (NE-NE)

CITADEL-204: R/R Marginal Zone Lymphoma

DG (N=72)

58.3 (46.1-69.8)

4.2 (0.9-11.7)

12.2 (8.1-17.5)

16.5 (11.5-20.6)

NR (NE-NE)

All (N=100)

58.0 (47.7-67.8)

6.0 (2.2-12.6)

12.2 (8.1-17.5)

16.5 (13.5-19.6)

NR (NE-NE)

CITADEL-205: R/R Mantle Cell Lymphoma (BTK Inhibitor Treatment Naive)

DG (N=77)

70.1 (58.6-80.0)

15.6 (8.3-25.6)

12.1 (9.0-NE)

13.6 (10.0-16.9)

NR (NE-NE)

All (N=108)

68.5 (58.9-77.1)

17.6 (10.9-26.1)

13.7 (9.0-19.9)

11.99 (8.3-16.9)

NR (NE-NE)

R/R: relapsed or refractory; ORR: objective response rate; CRR: complete response rate; mDOR: median duration of response (reported for responders); mPFS: median progression-free survival; mOS: median overall survival; DG: daily dosing group; NE: not estimable; NR: not reached.

Parsaclisib was generally well tolerated in all studies with a manageable safety profile.

"We are pleased to share these updated results from the CITADEL studies with the oncology community," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "The promising data add to the body of evidence that support parsaclisib, which has the potential to become a meaningful treatment for patients with relapsed or refractory follicular, marginal zone or mantle cell lymphomas, and we look forward to working with the FDA as we strive to bring this therapy to patients."

"Non-Hodgkin lymphoma is composed of varying subtypes and is one of the most common cancers in the United States. Given the fact that a significant subset of those afflicted will not be cured with current options, we need new treatment options," said Tycel Phillips, M.D., Primary Investigator, CITADEL-204 and Associate Professor, Division of Hematology and Oncology, Rogel Cancer Center, University of Michigan. "I am encouraged to see parsaclisib result in rapid and durable responses with a manageable safety profile in patients with a variety of non-Hodgkin lymphomas. The results observed across several key endpoints of the CITADEL studies suggest that parsaclisib may be a favorable treatment option for patients."

Presentations can be accessed via the ASH (Free ASH Whitepaper) website at View Source; #813 (Oral presentation, CITADEL-203), #44 (Oral presentation, CITADEL-204), #382 (Oral presentation, CITADEL-205).

About Follicular, Marginal Zone and Mantle Cell Lymphomas
Non-Hodgkin lymphoma (NHL) is a type of cancer that starts in the lymphocytes, a type of white blood cell. Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) are forms of B-Cell NHLs. FL and MZL are indolent or slow growing lymphomas; MCL is an aggressive or rapidly developing form. There is an unmet medical need for treatment options for patients who are relapsed or refractory to initial therapies.

About CITADEL
The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is evaluating parsaclisib in several ongoing studies as a treatment for adult patients with lymphomas, including:

CITADEL-203 (NCT03126019) is evaluating patients with relapsed or refractory follicular lymphoma (FL) Grade 1, 2 or 3a who received at least two prior systemic therapies, had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and were ineligible for hematopoietic stem cell transplantation (HSCT).
CITADEL-204 (NCT03144674) is evaluating patients with relapsed or refractory marginal zone lymphoma (MZL) who received at least one prior systemic therapy and were Bruton’s tyrosine kinase (BTK) inhibitor treatment naive. Patients with prior ibrutinib treatment were initially allowed to enroll; however, the cohort was terminated due to slow enrollment. Eligible patients had radiologically measurable lymphadenopathy or extranodal lymphoid malignancy (or histologically confirmed bone marrow infiltration in cases of splenic MZL), and an ECOG PS ≤2.
CITADEL-205 (NCT03235544) is evaluating patients with relapsed or refractory mantle cell lymphoma (MCL), who received one to three prior systemic therapies and were either naive to or were previously treated with a BTK inhibitor. Eligible patients had an ECOG PS ≤2, and radiologically measurable lymphadenopathy or extranodal lymphoid malignancy.
Patients eligible for each trial were allocated to receive parsaclisib 20 mg once daily for eight weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg once daily (daily-dosing group [DG]). Subsequently, daily dosing was selected as the preferred regimen and the WG patients were allowed to switch to DG. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required.

About Parsaclisib
Parsaclisib is a potent, highly selective, next-generation investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ). It is currently under evaluation as a monotherapy in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell); and autoimmune hemolytic anemia. Pivotal trials of parsaclisib in combination with ruxolitinib for the treatment of patients with myelofibrosis are underway; and there are plans to initiate trials to evaluate parsaclisib in combination with tafasitamab, including a pivotal trial in B-cell malignancies.

In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates, including parsaclisib. Under the terms of the agreement, Innovent has received the rights to develop and commercialize parsaclisib and two other assets in Mainland China, Hong Kong, Macau and Taiwan.