On May 14, 2020 NanOlogy, LLC, a clinical-stage oncology company, reported that updated data from two of its ongoing clinical trials were presented as abstracts last week through the DDW ePosters and ePresentations site (Press release, NanOlogy, MAY 14, 2020, View Source [SID1234558067]). The clinical trials are evaluating endoscopic ultrasound guided fine needle injection (EUS-FNI) of NanoPac (submicron particle paclitaxel) suspension for treatment of locally advanced pancreatic cancer (LAPC) and mucinous cystic neoplasms (MCNs/IPMNs) of the pancreas.

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 lead author of the abstract on intratumoral NanoPac for LAPC is Neil Sharma, MD (Parkview Cancer Institute – Fort Wayne, IN). The lead author of the abstract on intracystic NanoPac for MCNs/IPMNs is Mohamed O. Othman, MD (Baylor College of Medicine – Houston, TX).

Pancreatic Cancer

The Phase 2a dose-rising and expansion trial is evaluating over 6 months the safety and preliminary efficacy of NanoPac delivered intratumorally by EUS-FNI in patients with LAPC, concurrent with or following SOC therapy for the disease. After completing the dose-rising cohort (n=11), a dose expansion cohort has now fully enrolled (n=22) in which patients receive 2 monthly intratumoral (IT) injections of NanoPac. FDA has also recently allowed expansion of up to 30 additional patients who will receive up to 4 monthly IT injections.

Dr. Sharma’s abstract submitted to DDW in December 2019 reports data from the first 7 evaluable subjects from the dose expansion cohort. No drug-related local or systemic SAEs were reported including no reports of acute pancreatitis in any subject, 4 subjects had a partial response, 2 had stable disease, and 1 had progressive disease. Encouraging data has continued to accrue from the fully enrolled dose expansion (2- injection) cohort, which are expected to be presented later in 2020.

Pancreatic Cyst

The Phase 2a dose rising and expansion trial is evaluating over 6 months the safety and preliminary efficacy of NanoPac delivered intracystically by EUS-FNI following aspiration in patients with MCNs/IPMNs. The study has now completed enrollment (n=19) with patients in the dose expansion phase (n=8) receiving two intracystic injections of NanoPac 12 weeks apart.

Dr. Othman’s abstract also submitted in December reports data from the first 9 subjects who had completed the trial. No confirmed drug-related local or systemic SAEs were reported including no reports of acute pancreatitis. Plasma paclitaxel levels have not exceeded 1 ng/mL indicating that NanoPac particles are retained in the cyst over time. Evaluation of cyst volume showed decreases ranging from 8% to 89% in 8 subjects, 6 of whom showed a volume decrease > 50%. Cyst volume increased in 1 subject.

Based on encouraging results from both trials, NanOlogy is designing follow-on clinical protocols for evaluation by FDA.

In 2020, about 57,600 new cases of pancreatic cancer will be diagnosed in the U.S. and 47,050 people will die from the disease. Pancreatic cancer is currently the third most frequent cause of cancer related death in western countries and is predicted to become the second leading cause of death from cancer within the next 10 years. It is one of the few cancers for which no meaningful improvement in survival has been achieved over recent time with only an 8% survival rate at 5 years.

MCNs/IPMNs are a subset of pancreatic cysts that risk progression to pancreatic cancer. While estimates vary widely, as many as 30,000 new cases of high risk MCNs/IMPNs are diagnosed annually in the U.S. These patients may ultimately be required to undergo surgical resection of the pancreas to remove the lesion, a complicated procedure associated with high morbidity. No approved drug therapy exists in the U.S to treat the condition.

In addition to pancreatic neoplasms, NanOlogy clinical programs are advancing in genitourinary, peritoneal, lung, and dermal cancers.

The NanOlogy submicron particle therapeutic platform is based on a proprietary production technology that converts taxane API crystals into stable submicron particles of pure drug with disproportionate size to surface area ratio. The particles are covered by two composition of matter patents (US 9,814,685) and (10,507,195) both valid until 2036 in the US and pending globally.

On May 14, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported updated results from the Phase 1b/2 CARTITUDE-1 study (NCT03548207) evaluating the efficacy and safety of JNJ-4528, an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy in the treatment of patients with relapsed or refractory multiple myeloma (Press release, Janssen Pharmaceuticals, MAY 14, 2020, View Source [SID1234558066]).1 Longer-term follow-up results from the Phase 1b portion of the study (n=29); to be shared in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program (Abstract #8505), show that all patients responded to treatment and the responses were deep and durable, with 86 percent of patients achieving stringent complete response at a median follow-up of 11.5 months and 86 percent of patients being alive and progression free at nine months.1

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 100 percent overall response rate (ORR) included 97 percent of patients achieving a very good partial response or better and three percent achieving a partial response.1 Responses were observed among heavily pretreated patients (n=29) at a median administered dose 0.72×10 6 CAR+ viable T cells/kg. 1 Patients evaluated had received a median of five (range, 3-18) prior treatment regimens; 86 percent were triple-refractory and 28 percent were penta-refractory.1 The median time to first response was one month (range, 1-3) and 81 percent of evaluable patients (n=16) achieved minimal residual disease (MRD)-negative disease status at 10-5 or 10-6 at the time of first suspected complete response.1

"The longer-term results for JNJ-4528, as demonstrated through the latest findings from the CARTITUDE-1 study, show the continued treatment effect for heavily pretreated patients who faced a dismal prognosis," said Jesus G Berdeja, M.D., Director of Myeloma Research, Sarah Cannon Research Institute, and principal study investigator. "We’re encouraged by not only the relatively high rate of stringent complete responses, but also the progression-free survival seen in these patients."

"Janssen has a rich heritage in bringing transformational therapies to people living with blood cancers," adds Dr Patrick Laroche, M.D., Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. "I am excited to see these latest results support early promising data previously presented and hope that one day JNJ-4528 can offer a viable treatment option for multiple myeloma patients."

The most common adverse events (AEs) observed in CARTITUDE-1 were neutropenia (100 percent) and cytokine release syndrome (CRS, 93 percent).1 In patients who experienced Grade 3 and above AEs, the most common were neutropenia (100 percent), thrombocytopenia (69 percent) and leukopenia (66 percent). The median time of onset of CRS was seven days (range, 2-12) post-infusion, with a majority of patients experiencing Grade 1-2 CRS and two patients (7 percent) experiencing Grade 3 or greater CRS.1 Neurotoxicity consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in three patients (10 percent), including one patient (3 percent) with Grade 3 or greater toxicity.1 Three deaths were reported during the Phase 1b study: one due to CRS, one due to acute myeloid leukaemia (not treatment-related) and one due to progressive disease.1

"These recently updated data from the CARTITUDE-1 study suggest a durable response and tolerable safety profile for JNJ-4528," said Sen Zhuang, M.D., Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development, LLC. "We continue to advance the investigation of this novel CAR-T treatment with the goal of bringing a differentiated immunotherapy to patients with multiple myeloma, many of whom have exhausted all potential prior treatment options."

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicentre study evaluating the safety and efficacy of JNJ-4528 in adults with relapsed or refractory multiple myeloma, 97 percent of whom were refractory to the last line of treatment; 86 percent of whom were triple-class refractory meaning their cancer did not, or no longer responds to an immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody.1,2

The primary objective of the Phase 1b portion of the study was to characterise the safety and confirm the dose of JNJ-4528, informed by the first-in-human study with LCAR-B38M* CAR-T cells (LEGEND-2).2 Based on the safety profile observed in this portion of the study, outpatient dosing will be evaluated in additional CARTITUDE studies.1 The Phase 2 portion of the study will evaluate the efficacy of JNJ-4528 with overall response as the primary endpoint.2

About JNJ-4528 (LCAR-B38M*)

JNJ-4528 (LCAR-B38M) is an investigational chimeric antigen receptor T cell (CAR-T) therapy for the treatment of patients with relapsed or refractory multiple myeloma. The design comprises a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies.1 CAR-T cells are an innovative approach to eradicating cancer cells by harnessing the power of a patient’s own immune system.3 BCMA is a protein that is highly expressed on myeloma cells.4

In December 2017, Janssen entered into an exclusive worldwide license and collaboration agreement with Legend Biotech to develop and commercialise JNJ-4528 (LCAR-B38M).5 In May 2018, Janssen initiated the Phase 1b/2 CARTITUDE-1 trial (NCT03548207) to evaluate the efficacy and safety of JNJ-4528 in adults with relapsed or refractory multiple myeloma, informed by the LEGEND-2 study results.2

In April 2019, JNJ-4528 was granted PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA).6 PRIME offers enhanced interaction and early dialogue to optimise drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.7 In February 2020, the European Commission granted orphan designation for JNJ-4528.8

About Multiple Myeloma

Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.9 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.10 Around 50 percent of newly diagnosed patients do not reach five-year survival,11,12 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.13

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.14 Refractory MM is when a patient’s disease progresses within 60 days of their last therapy.15 Relapsed cancer is when the disease has returned after a period of initial, partial or complete remission.15 While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.16 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.17

*LCAR-B38M identifies the investigational product in China, sponsored by Janssen’s development partner, Legend Biotech.

On May 14, 2020 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ:MOR) and Incyte (NASDAQ:INCY) reported updated results from the ongoing Phase 2 L-MIND study investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) (Press release, MorphoSys, MAY 14, 2020, View Source [SID1234558065]). The results, based on a November 30, 2019 data cut-off, corroborate previously reported primary analysis data.

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!

In this long-term analysis of the L-MIND data, 80 study patients receiving tafasitamab plus lenalidomide were included in the efficacy analysis. After a minimum of two years’ follow-up, outcomes from the L-MIND study are consistent with the primary analysis and confirm the durability of the response (DoR) and overall survival (OS) of tafasitamab in combination with lenalidomide followed by tafasitamab monotherapy in autologous stem cell transplantation (ASCT)-ineligible patients with r/r DLBCL. Assessment by an independent review committee (IRC) at data cut-off showed an objective response rate (ORR) of 58.8% (47 out of 80 patients) and a complete response (CR) rate of 41.3% (33 out of 80 patients). Median duration of response (mDOR) was 34.6 months, with median overall survival (mOS) of 31.6 months and median progression-free survival (mPFS) of 16.2 months. The safety profile was consistent with that observed in previously reported studies of tafasitamab in combination with lenalidomide. The full analysis will be presented virtually at the 25th EHA (Free EHA Whitepaper) Annual Congress to be held June 11-14, 2020.

"We are extremely encouraged by the long-term data from our L-MIND study which confirms the previously reported results from the primary analysis," commented Dr. Malte Peters, Chief Research and Development Officer, MorphoSys. "Tafasitamab in combination with lenalidomide has the potential to address the significant medical need in patients suffering from r/r DLBCL, and we are working diligently towards our key priority of making tafasitamab available to eligible patients."

"The updated data for L-MIND reinforce the potential of tafasitamab in combination with lenalidomide as treatment for patients with r/r DLBCL. We look forward to working with our partners at MorphoSys as we seek to bring this new therapeutic option to eligible patients globally," Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapeutics, Incyte.

A Biologics License Application (BLA) for tafasitamab in combination with lenalidomide for r/r DLBCL is currently under Priority Review by the U.S. Food and Drug Administration (FDA) (PDUFA action date August 30, 2020). The BLA is based on data including the primary analysis of L-MIND with a previous cut-off date as of November 30, 2018, and the primary analysis data from the retrospective observational matched control cohort Re-MIND evaluating efficacy outcomes of r/r DLBCL patients who received lenalidomide monotherapy.

In January 2020, MorphoSys and Incyte Corporation entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. If approved, MorphoSys and Incyte will co-commercialize tafasitamab in the United States while Incyte has exclusive commercialization rights outside the United States.

About L-MIND
L-MIND is a single arm, open-label Phase 2 study, investigating the combination of tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) after up to two prior lines of therapy, including an anti-CD20 targeting therapy (e.g. rituximab), who are not eligible for high-dose chemotherapy and subsequent autologous stem cell transplantation. The study’s primary endpoint is objective response rate (ORR). Secondary outcome measures include duration of response (DoR), progression-free survival (PFS) and overall survival (OS). In May 2019, the study reached its primary completion. Primary analysis data with a cut-off date of November 30, 2018 included 80 patients enrolled into the trial who had received tafasitamab and lenalidomide and had been followed-up as per protocol for at least one year. Efficacy results in this update were based on response rates assessed by an independent review committee for all 80 patients.

About Re-MIND
Re-MIND, an observational retrospective study, was designed to isolate the contribution of tafasitamab in the combination with lenalidomide and to prove the combinatorial effect. The study compares real-world response data of patients with relapsed or refractory DLBCL who received lenalidomide monotherapy with the efficacy outcomes of the tafasitamab-lenalidomide combination, as investigated in MorphoSys’ L-MIND trial. Re-MIND collected the efficacy data from 490 r/r DLBCL patients in the U.S. and EU. Qualification criteria for matching patients of both studies were pre-specified. As a result, 76 eligible Re-MIND patients were identified and matched 1:1 to 76 of 80 L-MIND patients based on important baseline characteristics. Objective response rates (ORR) were validated based on this subset of 76 patients in Re-MIND and L-MIND, respectively. The primary endpoint of Re-MIND has been met and shows a statistically significant superior best ORR of the tafasitamab/lenalidomide combination compared to lenalidomide monotherapy.

About tafasitamab
Tafasitamab is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. In January 2020, MorphoSys and Incyte Corporation entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. If approved in the U.S., MorphoSys and Incyte will co-commercialize tafasitamab; Incyte will have exclusive commercialization rights outside the U.S. Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials, including L-MIND and Re-MIND. Additionally, tafasitamab is being evaluated as part of the ongoing Phase 3 study B-MIND study assessing the combination of tafasitamab and bendamustine versus rituximab and bendamustine in r/r DLBCL. Tafasitamab is also currently being investigated in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.

On May 14, 2020 CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported that new data from two ongoing Phase 1/2 clinical trials of the CRISPR/Cas9 gene-editing therapy CTX001 in severe hemoglobinopathies have been accepted for an oral presentation at the EHA (Free EHA Whitepaper) Congress, which will take place virtually from June 11-14, 2020 (Press release, CRISPR Therapeutics, MAY 14, 2020, View Source [SID1234558064]).

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!

An abstract posted online today includes 12 months of follow-up data for the first patient treated in the ongoing Phase 1/2 CLIMB-111 trial in transfusion-dependent beta thalassemia (TDT) and 6 months of follow-up data for the first patient treated in the ongoing Phase 1/2 CLIMB-121 trial in severe sickle cell disease (SCD). Updated data will be presented at EHA (Free EHA Whitepaper), including longer duration follow-up data for the first two patients treated in these trials and initial data for the second patient treated in the CLIMB-111 trial.

The accepted abstract is now available on the EHA (Free EHA Whitepaper) conference website: View Source

Abstract Title: Initial Safety and Efficacy Results With a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Hematopoietic Stem and Progenitor Cells in Transfusion-Dependent β-Thalassemia and Sickle Cell Disease
Session Title: Immunotherapy – Clinical
Abstract Code: S280

About the Phase 1/2 Study in Transfusion-Dependent Beta Thalassemia
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with TDT. The study will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up study.

About the Phase 1/2 Study in Sickle Cell Disease
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 18 to 35 with severe SCD. The study will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up study.

About CTX001
CTX001 is an investigational ex vivo CRISPR gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth and is then replaced by the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and painful and debilitating sickle crises for SCD patients. CTX001 is the most advanced gene-editing approach in development for beta thalassemia and SCD.

CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex.

About the CRISPR-Vertex Collaboration
CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first treatment to emerge from the joint research program. CRISPR Therapeutics and Vertex will jointly develop and commercialize CTX001 and equally share all research and development costs and profits worldwide.

On May 14, 2020 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that four abstracts containing new clinical data and analyses related to imetelstat, the Company’s first-in-class telomerase inhibitor, have been accepted for presentation at the Virtual Edition of the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress to be held online from June 11-14, 2020 (Press release, Geron, MAY 14, 2020, View Source [SID1234558063]). The abstracts are available on the EHA (Free EHA Whitepaper) website at www.ehaweb.org/congress.

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 pleased to report very encouraging durability data from the IMerge Phase 2 clinical trial to be presented at the upcoming EHA (Free EHA Whitepaper) Annual Congress, including a median duration of 8-week transfusion independence of 88 weeks, which is the longest duration we have reported to date in this trial, and that 29% of patients were transfusion free for more than one year," said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer. "We are also pleased that the potential survival benefit associated with imetelstat treatment in the IMbark Phase 2 clinical trial for patients relapsed or refractory to JAK inhibitors was correlated with other clinical benefits observed in the trial, such as symptom response, spleen volume reduction and improvement in fibrosis."

Updated Efficacy and Safety Data from the IMerge Phase 2 Clinical Trial

IMerge is a two-part Phase 2/3 clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (lower risk MDS), who are relapsed after or refractory to prior treatment with erythropoiesis stimulating agents (ESAs). The primary efficacy endpoint of IMerge is 8-week red blood cell transfusion independence (RBC-TI) rate, defined as the proportion of patients not receiving any RBC transfusion during any consecutive eight weeks since entry into the trial. Key secondary endpoints include 24-week RBC-TI rate and the rate of hematologic improvement-erythroid (HI-E), defined as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

Abstract Title: Treatment with Imetelstat Provides Durable Transfusion Independence (TI) in Heavily Transfused Non-del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs)

The abstract, accepted for an oral presentation, reports long-term efficacy and safety data from 38 patients in the IMerge Phase 2 clinical trial, based on a February 4, 2020 cut-off date and a median follow-up of 24 months.

Key data highlights from the abstract:

75% of the 16 (42%) 8-week RBC-TI responders showed a hemoglobin rise of > 3 g/dL during the transfusion-free interval when compared to pretreatment level.
12 patients (32%) achieved a 24-week RBC-TI.
11 patients (29%) were transfusion free for more than one year, and the longest transfusion free interval was 2.7 years.
Median RBC-TI duration was 88 weeks, the longest reported to date in the trial.
HI-E was achieved by 26 patients (68%) with a median duration of 93 weeks.
Cytogenetic and mutational malignant clone reduction in some patients indicates potential disease-modifying activity of imetelstat.
Most frequently reported adverse events were manageable and reversible grade > 3 cytopenias.
Oral Presentation Details:
Session Title: Novel Treatments for MDS I
Abstract Code: S183
Please check www.ehaweb.org/congress for updates regarding the virtual presentation schedule.

New Analyses of Data from IMbark Phase 2 Clinical Trial

IMbark was designed as a Phase 2 clinical trial to evaluate two dosing regimens of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in patients with Intermediate-2 or High-risk myelofibrosis (MF) who have relapsed after or are refractory to prior treatment with a janus kinase inhibitor (JAKi). The co-primary efficacy endpoints for IMbark were spleen response rate, defined as the proportion of patients who achieve a reduction of at least 35% in spleen volume as assessed by imaging, and symptom response rate, defined as the proportion of patients who achieve a reduction of at least 50% in Total Symptom Score (TSS), at 24 weeks. Key secondary endpoints were overall survival (OS) and safety.

Abstract Title: Favorable Overall Survival with Imetelstat Treatment Correlates with Other Clinical Benefits in Intermediate-2 or High-Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor

The abstract, accepted for a poster presentation, reports new analyses of data from all 107 patients in both arms (59 patients in the 9.4 mg/kg arm and 48 patients in the 4.7 mg/kg arm) of the IMbark Phase 2 clinical trial with a data cut-off date of February 19, 2020 and a median follow-up of 41.7 months. As of the data cut-off date, median OS was 28.1 months in the 9.4 mg/kg arm and 19.9 months in the 4.7 mg/kg arm. The new analyses report a trend of longer OS in patients who achieved symptom response, spleen volume reductions ranging from > 10% to > 35%, and improvement in bone marrow fibrosis. The abstract concludes that these data show dose-related improvements in OS with imetelstat in patients who are relapsed/refractory to JAKi and that the potential survival benefit observed in IMbark with imetelstat was supported by the trend of correlation with other clinical benefits, such as symptom response and spleen volume reduction, as well as fibrosis improvement.

Poster Presentation Details:
Session Title: Myeloproliferative neoplasms—Clinical
Abstract Code: EP1107
Please check www.ehaweb.org/congress for updates regarding when EHA (Free EHA Whitepaper) e-Poster presentations are scheduled to be available.

Abstract Title: Imetelstat Treatment Results in Clinical Benefits, Including Improved Overall Survival, in Patients with Higher-Risk Triple Negative Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitors (JAKI)

The abstract, accepted for a poster presentation, presents new analyses of clinical outcomes, including OS, in triple-negative (TN) patients enrolled in the IMbark Phase 2 clinical trial. Triple-negative MF patients lack the three driver mutations of the disease, JAK2, CALR or MPL, which represents a high-risk molecular signature. These patients have a higher incidence of leukemic transformation and approximately 3-year overall survival from diagnosis when compared to non-TN patients. The abstract concludes that TN patients treated with 9.4 mg/kg in the IMbark Phase 2 clinical trial had better clinical outcomes, such as spleen and symptom response as well as better improvement in fibrosis and OS, when compared to non-TN patients. These data suggest that imetelstat may overcome the poor outcomes expected with TN patients.

Poster Presentation Details:
Session Title: Myeloproliferative neoplasms—Clinical
Abstract Code: EP1101
Please check www.ehaweb.org/congress for updates regarding when EHA (Free EHA Whitepaper) e-Poster presentations are scheduled to be available.

Abstract Title: Telomerase Activity, Telomere Length and hTERT Expression Correlate with Clinical Outcomes in Higher-Risk Myelofibrosis (MF) Relapsed/Refractory (R/R) to Janus Kinase Inhibitor Treated with Imetelstat

The abstract, accepted for a poster presentation, reports biomarker results and their correlation with the clinical benefits of treatment with imetelstat in patients from the IMbark Phase 2 clinical trial. These results showed dose-dependent inhibition of the telomerase target, as evaluated by reductions in telomerase activity, human reverse transcriptase (hTERT) levels and telomere length, in the IMbark patients treated with imetelstat, and this on-target activity correlated with clinical responses and longer OS. In addition, dose-dependent reduction in variant allele frequency of driver mutations was noted, indicating imetelstat targets the underlying malignant clone. The abstract concludes that these data are consistent with telomere biology in cancer cells and provide evidence for the on-target mechanism of action of imetelstat through telomerase inhibition.

Poster Presentation Details:
Session Title: Myeloproliferative neoplasms—Clinical
Abstract Code: EP1098
Please check www.ehaweb.org/congress for updates regarding when EHA (Free EHA Whitepaper) e-Poster presentations are scheduled to be available.

In accordance with EHA (Free EHA Whitepaper) policies, abstracts submitted to the EHA (Free EHA Whitepaper) Annual Congress are embargoed from the time of submission. To be eligible for presentation at the EHA (Free EHA Whitepaper) Annual Congress, any additional data or information to be presented at the Annual Congress may not be made public before the presentation. The slide presentation and posters will be available at www.geron.com/r-d/publications following the EHA (Free EHA Whitepaper) Annual Congress presentations.

Post-EHA Event with Key Opinion Leaders

In June, Geron plans to host a webcasted event after the EHA (Free EHA Whitepaper) Annual Congress. At the event, authors from each of the imetelstat abstracts will reprise the respective presentations from the EHA (Free EHA Whitepaper) Annual Congress. A press release with event details, including how to access a webcast link, will be available on Geron’s website at the beginning of June 2020.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the apoptosis of malignant stem and progenitor cells, which allows potential recovery of normal hematopoiesis. Clinical studies of imetelstat sponsored by Geron include IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMbark, a Phase 2 trial in Intermediate-2 or High-risk myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.