On June 11, 2021 Ryvu Therapeutics (WSE:RVU) reported the online publication of two posters and an oral presentation demonstrating clinical and pre-clinical activity of its selective CDK8/19 inhibitor RVU120 (previously SEL120) and the dual PIM/FLT3 inhibitor SEL24 (MEN1703), in-licensed by Menarini Group from Ryvu Therapeutics, at the Annual European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress (Press release, Ryvu Therapeutics, JUN 11, 2021, View Source [SID1234583913])Annual European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress.

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RVU120: orally available CDK8/19 inhibitor

RVU120 (SEL120) is a highly selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in in vitro and in vivo models as well as in onco-hematological malignancies. The first-in-human (FIH) Phase I study with RVU120, in relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HRMDS), is being conducted at 5 investigational sites in the US (View Source).

The data presented at EHA (Free EHA Whitepaper) 2021 covers the first four dose cohorts, in which RVU120 demonstrated favorable safety and PK profile. No DLTs were observed, and all of the reported SAEs were assessed as unlikely or not related to study drug.

Results are reported on the first five patients to receive treatment with RVU120, and the clinically relevant responses were observed in patients in the two highest dose cohorts reported:

The Cohort 3 (50mg dose, subsequently escalated to 75 mg) patient, with HRMDS, demonstrated an erythroid response from Cycle 5 to Cycle 8 and continues on RVU120 treatment in Cycle 13 with stable disease. An erythroid response reflects a reduction in red blood cell transfusions vs. baseline.
The Cohort 4 (75mg dose) patient, with relapsed/refractory AML, showed a response from C2 with persistence of skin leukemia, which completely resolved at C7 resulting in a CR. This patient was previously refractory to venetoclax + HMA, which is a patient population associated with poor prognosis.
Furthermore, translational data will be presented as part of an Oral Session and provide a potential linkage between in vitro data showing erythroid differentiation and erythroid response in the clinic. In vitro data demonstrate that RVU120 can induce erythroid cells to differentiate and therefore rescue anemia in preclinical models.

Presented results indicate strong erythroid differentiation potential of RVU120 (SEL120) in (Lin-) CD34+, that acquired genetic abnormalities resulting in arrested erythroid commitment, a characteristic of many MDS and AML subtypes. Detailed transcriptomic profiling strongly associated differentiation with enrichment of genes representing regulators of erythroid commitment and hemoglobin metabolism. Further studies are warranted to investigate efficacy of RVU120 (SEL120) in anemias associated with bone marrow failures in AML and MDS patients.

"We are excited to see early signs of clinical efficacy for RVU120 in both AML and high risk MDS patients who were previously treated with multiple lines of therapy. These patients had poor prognosis prior to treatment with RVU120, so we anticipate that RVU120 could serve an area of high unmet medical need. The translation of erythroid differentiation in vitro to potential erythroid responses in patients is an exciting clinical benefit as these patients require fewer red blood cell transfusions" – said Setareh Shamsili, MD, PhD, Chief Medical Officer and EVP at Ryvu Therapeutics.

Oral Presentation: "RVU120/SEL120 CDK8/19 inhibitor – a drug candidate for the treatment of MDS can induce erythroid differentiation in transformed CD34+ hematopoietic progenitor cells" (S164)

Presentation ID: p412-5
Date and Time: on-demand video recording is now available, followed by a Live Q&A Session on Wednesday, June 16 (13:00 – 13:45 CEST)
Poster Presentation: "CLI120-001 Phase1b Study of SEL120/RVU120 in patients with AML or High Risk MDS: Preliminary clinical and PK results from initial dose escalation cohorts" (EP480)

Poster ID: EP480
SEL24/MEN1703: orally available dual PIM/FLT3 inhibitor

A clinical poster on the first-in-human study of SEL24/MEN1703, the DIAMOND-01 trial conducted by Ryvu’s partner Menarini Group, reports four objective responses across the dose escalation (n=25) and cohort expansion (n=23) in patients with AML, with 3 of those 4 responders harboring an IDH mutation. Notably, three out of five patients with IDH mutations treated at doses of 75-125 mg achieved a CR/CRi, including a patient that relapsed on the IDH-inhibitor enasidenib. Furthermore, one patient with an IDH1 mutation achieved a CRi and underwent allogeneic-HSCT.

At the recommended dose (n=30) of 125mg/day as selected in the dose escalation phase, SEL24/MEN1703 showed a manageable safety profile. Most Grade 3 or higher treatment-emergent adverse events (TEAEs) were hematologic or infectious in nature.

"We are thrilled to share encouraging results for SEL24 (MEN1703) in treating patients with Acute Myeloid Leukemia," said Dirk Laurent, M.D., Global Therapeutic Area Head – Oncology at Menarini Ricerche, the R&D division of the Menarini Group. "The data, which is presented in our posters at both ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) annual meetings, provides a strong rationale for further clinical development, including the potential to focus on a molecularly defined subset of patients – AML patients with IDH mutations. This accomplishment reflects our sustained commitment to improving the lives of patients with difficult-to-treat cancer and underscores the value of our precision oncology approach."

Poster Presentation: "Results from DIAMOND-01 (CLI24-001) TRIAL: First in Human Study of SEL24/MEN1703, a Dual PIM/FLT3 Kinase Inhibitor, in Patients with Acute Myeloid Leukemia" (EP455)

Poster ID: EP455
All presentations and posters are now available online and can be obtained from conference site: View Source View Source

On June 11, at 1:00 PM CEST (7:00 AM ET), Ryvu Therapeutics will hold a conference call to discuss the data presented at EHA (Free EHA Whitepaper) 2021. Join the call at: live.ryvu.com
(or View Source)

About RVU120 (SEL120)

RVU120 (SEL120) is a selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in in vitro and in vivo models as well as in onco-hematological malignancies. The first-in-human (FIH) phase I study with RVU120, in relapsed or refractory AML or high-risk myelodysplastic syndromes (HRMDS), is currently enrolling patients at 5 investigational sites in USA (View Source).

Translational data suggest that RVU120 is particularly effective in undifferentiated AML STAT5-positive cancers. Administration of RVU120 in orthotopic AML patient derived xenograft models reduced tumor burden to the level undetectable in the peripheral blood, decreased splenomegaly and resulted in partial bone marrow recovery at well tolerated doses.

In addition, RVU120 has demonstrated single agent efficacy in multiple solid tumor models. On May 28, 2021, Ryvu’s Clinical Trial Application (CTA) to commence a single-agent, open-label Phase I/II trial, investigating the safety and efficacy of RVU120 (SEL120) in patients with relapsed/refractory metastatic or advanced solid tumors, was approved by the Polish Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, and the respective Central Ethics Committee.

On March 25, 2020, the U.S. Food and Drug Administration (FDA) granted an orphan drug designation (ODD) to RVU120, for the treatment of patients with acute myeloid leukemia (AML).

On April 7, 2021, U.S. Food and Drug Administration, FDA, placed a partial clinical hold on the first in human Phase Ib, dose escalation clinical trial of RVU120 in patients with relapsed/refractory (R/R) AML and high-risk MDS. Patients who are currently taking RVU120 may continue treatment. Ryvu continues to work closely with the FDA to resolve the partial clinical hold with the objective of resuming enrollment in the study.

RVU120 (SEL120) has been internally discovered by Ryvu and has received support from the Leukemia & Lymphoma Society Therapy Acceleration Program (TAP), a strategic initiative to partner directly with innovative biotechnology companies and leading research institutions to accelerate the development of promising new therapies for blood cancers.

About SEL24 (MEN1703)

SEL24 (MEN1703), a first-in-class, orally available, dual PIM/FLT3 kinase inhibitor discovered and initially developed by Ryvu Therapeutics and licensed to the Menarini Group. SEL24 (MEN1703) is currently evaluated in DIAMOND-01 trial (CLI24-001; clinicaltrials.gov identifier NCT03008187), a First-in-Human, Phase I/II, dose escalation and cohort expansion trial, as single agent for the treatment of patients with Acute Myeloid Leukemia (AML).

In the dose escalation part of DIAMOND-01 trial, SEL24 (MEN1703) demonstrated a manageable safety profile up to the recommended dose (RD) of 125 mg/day, along with initial evidence of anti-leukemic activity in a single agent setting, particularly in patients with IDH mutant disease either naïve or previously exposed to IDH inhibitors, warranting further investigation of the compound in molecularly defined subset of patients.

On June 11, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the latest data from three pivotal phase III studies of Venclexta/Venclyxto (venetoclax) – CLL14, MURANO and VIALE-A – to be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress, June 9-17 (EHA2021) (Press release, Hoffmann-La Roche, JUN 11, 2021, View Source [SID1234583877]). Long-term follow-up data from the CLL14 and MURANO studies support the primary analysis of Venclexta/Venclyxto in chronic lymphocytic leukaemia (CLL) and the possibility of tailoring treatment approaches based on genetic risk factors. Furthermore, the latest research shows the potential of minimal residual disease (MRD) as a key measure of disease response in CLL and acute myeloid leukaemia (AML).

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"The data from these Venclexta/Venclyxto combinations support our continued commitment to provide valuable therapeutic options for patients with hard-to-treat blood cancers," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "These data also advance our understanding of minimal residual disease, which we believe is a useful endpoint that may help identify patients more quickly who are in need of additional treatment."

Four-year follow-up analysis of the phase III CLL14 study
This four-year post-hoc analysis of investigator-assessed progression-free survival (PFS) had a median follow-up of 52.4 months (interquartile range: 49.5-56.2 months). The fixed treatment duration (12 months) study indicated that the chemotherapy-free Venclexta/Venclyxto plus Gazyva/Gazyvaro (obinutuzumab) regimen had an estimated PFS rate of 74.0% vs 35.4% for Gazyva/Gazyvaro plus chlorambucil. Importantly, the time to next treatment (TTNT) was significantly longer among patients treated with the Venclexta/Venclyxto plus Gazyva/Gazyvaro regimen versus the comparator (four-year TTNT 81.1% vs 59.9%; HR 0.46, 95% CI [0.32-0.65], p<0.0001).1

Furthermore, 30 months after the end of treatment, 26.9% of the Venclexta/Venclyxto-treated patients still had undetectable MRD (uMRD) compared with 3.2% of those treated with the comparator.1 Undetectable MRD, sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.4 Undetectable MRD is emerging as a measure of disease response that may be useful to consider in treatment decision-making.

Common grade 3-4 adverse events with Venclexta/Venclyxto and Gazyva/Gazyvaro at 28 months follow-up were low white blood cell count and infections.5

Substudy from the phase III MURANO study
Results from this substudy suggested that increased prevalence of certain unfavourable genetic risk factors negatively impacted the MRD response of patients who were retreated with Venclexta/Venclyxto plus MabThera/Rituxan (rituximab) after progression on treatment with that regimen. These data indicate the potential to tailor treatment approaches for patients with previously treated CLL based on genetic risk factors.2

Post-hoc analysis of the phase III VIALE-A study
Additionally, a post-hoc analysis from the phase III VIALE-A study suggested the value of continued research to understand the role of MRD monitoring in AML. In the analysis, patients who achieved a composite complete remission and uMRD following treatment with Venclexta/Venclyxto and azacitidine, a hypomethylating agent, had improved survival outcomes compared with those who were MRD-positive following treatment. The 12-month estimates for duration of response, overall survival and event-free survival for both groups are listed below:

Achieved composite complete remission and uMRD (MRD<10-3) Did not achieve composite complete remission and uMRD (MRD≥10-3)
Duration of response 81.2% (95% CI 69.3-88.9) 46.6% (95% CI 35.6-56.8)
Overall survival 94.0% (95% CI 84.7-97.7) 67.9% (95% CI 57.6-76.2)
Event-free survival 83.2% (95% CI 71.6-90.3) 45.4% (95% CI 35.2-55.0)
Adverse events of grade ≥3 (MRD<10-3/MRD≥10-3) were febrile neutropenia (50%/43%), neutropenia (50%/35%), and thrombocytopenia (44%/44%), similar to the overall population.3

Roche is collaborating with regulatory authorities and others in the industry to advance understanding of MRD. The company continues to investigate Venclexta/Venclyxto in a robust clinical development programme, including in the phase III CRISTALLO trial in previously untreated CLL, which uses MRD as a primary endpoint.

Venclexta/Venclyxto is approved in the US and EU in combination with MabThera/Rituxan for the treatment of adult patients with CLL who have received at least one prior therapy; in combination with Gazyva/Gazyvaro for the treatment of adult patients with previously untreated CLL; and as a monotherapy for the treatment of CLL in the presence of 17p deletion or TP53 mutation in people who are unsuitable for or have failed a B-cell receptor pathway inhibitor.

Venclexta is also approved in the US in combination with azacitidine, decitabine, or low dose cytarabine for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. In the EU, Venclyxto is approved in combination with a hypomethylating agent for the treatment of adult patients with newly diagnosed AML who are ineligible for intensive chemotherapy.

About the CLL14 study
CLL14 [NCT02242942] is a randomised phase III study evaluating the combination of fixed-duration Venclexta/Venclyxto (venetoclax) plus Gazyva/Gazyvaro (obinutuzumab) compared to Gazyva/Gazyvaro plus chlorambucil in adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions. Four hundred and thirty-two patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta/Venclyxto alongside six-month duration of Gazyva/Gazyvaro (Arm A) or six-month duration of Gazyva/Gazyvaro alongside 12-month duration of chlorambucil (Arm B). Arm A started with an initial dosing of Gazyva/Gazyvaro followed by a five-week Venclexta/Venclyxto dose ramp-up to help reduce the risk of tumour burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints included PFS assessed by independent review committee, minimal residual disease status, overall response rate, complete response rate, and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.

About the MURANO study
MURANO [NCT02005471] is a phase III open-label, international, multicentre, randomised study evaluating the efficacy and safety of fixed-duration Venclexta/Venclyxto (venetoclax) in combination with MabThera/Rituxan (rituximab) compared to bendamustine in combination with MabThera/Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta/Venclyxto, patients on the Venclexta/Venclyxto plus MabThera/Rituxan arm received six cycles of Venclexta/Venclyxto plus MabThera/Rituxan followed by Venclexta/Venclyxto monotherapy for up to two years total. The study included 389 patients with chronic lymphocytic leukaemia (CLL), with or without 17p deletion, who had been previously treated with at least one line of therapy. A substudy from 2018 onward enrolled 34 relapsed or refractory CLL patients who progressed after initial treatment to receive Venclexta/Venclyxto plus MabThera/Rituxan as retreatment (n=25) or who crossed over from the BR arm (n=9). The primary endpoint of the study was progression-free survival. Secondary endpoints included overall survival, overall response rate and complete response rate (with or without complete blood count recovery).

About the VIALE-A study
VIALE-A [NCT02993523] is a phase III, randomised, double-blind, placebo-controlled multicentre study evaluating the efficacy and safety of Venclexta/Venclyxto (venetoclax) plus azacitidine, a hypomethylating agent, compared to placebo with azacitidine, in 431 people with previously untreated acute myeloid leukaemia who are ineligible for intensive chemotherapy. Two-thirds of patients (n=286) received 400 mg Venclexta/Venclyxto daily, in combination with azacitidine, and the remaining patients (n=145) received placebo tablets in combination with azacitidine. Patients enrolled in the study had a range of mutational subtypes, including IDH1/2 and FLT3. VIALE-A met its primary and key secondary endpoints.

About Venclexta/Venclyxto
Venclexta/Venclyxto (venetoclax) is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche group, in the US and commercialised by AbbVie outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood cancers.

In the US, Venclexta has been granted five Breakthrough Therapy Designations by the U.S. Food and Drug Administration: one for previously untreated chronic lymphocytic leukaemia (CLL), two for relapsed or refractory CLL and two for previously untreated acute myeloid leukaemia.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting FcRH5 and CD3; Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On June 11, 2021 ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, reported that new data presented by John Daly from the academic lab of CSO, Prof. Michael O’Dwyer at the Annual European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress illustrating the merit of knocking out the checkpoint inhibitory receptor for CD96 on NK cells in the context of MM (Press release, ONK Therapeutics, JUN 11, 2021, View Source [SID1234583898]).

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The data is based on research studies carried out at the National University of Ireland, Galway (NUI Galway), College of Medicine, Nursing and Health Sciences, by Prof. O’Dwyer’s academic research group.

Contradictory data had previously shown that CD96 could be both an activating and an inhibitory receptor on human NK cells, depending on the tumor type being examined. The data presented during the poster presentation demonstrate conclusively that in the case of MM cells expressing CD155, CD96 is a human NK cell inhibitory receptor, regulating both cytotoxicity and cytokine release. Experiments using CRISPR/Cas9-mediated KO of CD96 in primary NK cells resulted in enhanced cytotoxicity and cytokine release compared to controls. Studies carried out in parallel also demonstrated a similar beneficial effect of CRISPR/Cas9-mediated KO of TIGIT in primary NK cells.

Furthermore, NK cells obtained from MM patient bone marrow had particularly high levels of CD96 expression, suggesting NK cells in the bone marrow of MM patients are more likely to be susceptible to CD155 mediated immune-evasion.

These new insights support knocking out inhibitory checkpoint receptors, including CD96 KO and TIGIT KO as a promising approach to improving the functionality of off-the-shelf engineered NK cell therapies for the treatment of cancer.

E-poster presentation title: Knockout of CD96 or TIGIT using CRISPR/Cas9 enhances NK induced
cytotoxicity and cytokine production in the presence of CD155 expressing myeloma cells.

Author(s)/Presenters: John Daly, Mark Gurney, Michael O’Dwyer.

Session title: Myeloma and other monoclonal gammopathies – Biology & Translational Research.

Abstract number: EP941

Date and Time: Available on the virtual platform as an e-poster Friday, June 11 at 9:00 CEST.

Download a copy HERE.

Chris Nowers, ONK Therapeutics’ CEO said, "The studies carried out by Prof. O’Dwyer’s academic research group are expanding our deep understanding of NK cell biology and are helping to confirm certain gene constructs and edits that will enhance NK cell cytotoxicity, cytokine production and persistence in the tumor microenvironment. Gene edited NK cells lacking CD96 and/or TIGIT could therefore be beneficial for treating CD155 expressing malignancies, such as Multiple Myeloma."

ONK Therapeutics was formed based on technology and intellectual property developed at NUI Galway by Prof. O’Dwyer. The Company is developing off-the-shelf, optimized NK cell therapies for cancer that utilize dual-targeting of the death receptor pathway in addition to incorporating a CAR, along with further strategies that utilize novel gene editing approaches to enhance persistence, metabolic profile, and cytotoxic potential. ONK has exclusive licenses to a broad intellectual property (IP) against a wide range of NK cell checkpoints, including CD96 and TIGIT.

On June 11, 2021 Shanghai Yingli Pharmaceuticals Ltd (Yingli Pharma), a clinical stage pharmaceutical company providing new therapies for cancer and metabolic diseases, reported the topline data from a clinical trial sponsored by the company at the annual meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) being held June 9-17, 2021 (Press release, Yingli Pharmaceutical, JUN 11, 2021, View Source [SID1234583915]).

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The study entitled ‘A Phase 2 study of an oral PI3Kδ inhibitor YY-20394 in patients with relapsed or refractory follicular lymphoma’ will be presented at EHA (Free EHA Whitepaper) by Dr. Lugui Qiu, a lead investigator from Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China. This is a registration study that enrolled 93 relapsed or refractory Follicular Lymphoma (FL) patients having received 2 or more prior systemic therapies and was conducted at 32 clinical sites in China. Linperlisib was evaluated as a monotherapy for safety, tolerability and efficacy at recommended phase 2 dose of 80 mg once daily. Following a data cutoff on March 15, 2021, the fully enrolled study was analyzed for 89 evaluable patients. The Overall Response Rate (ORR) was 79.5%, with 12.4% Complete Response, 67.4% Partial Response, and 16.1% Stable Disease, combining to achieve a Disease Control Rate of 96.6%. Previously, the Phase 1 study of linperlisib had shown similar preliminary efficacy of 90% ORR in 10 patients with r/r FL. As of the data cutoff for the Phase 2, the median Progression Free Survival was 11.8 months, and the Duration of Response was 12.3 months. Forty seven patients were continuing to receive linperlisib treatment.

Follicular Lymphoma is increasingly harder to treat if patients progress on previous therapies, usually immuno-chemotherapy is a mainstay as a prior treatment. On this study, 65% of the patients had received 3 or more prior systemic treatments, and all patients had previously received rituximab-based therapies.

The safety data from the FL Phase 2 study indicated that linperlisib was generally safe and tolerable with manageable adverse events. Most of the adverse events were Grade 1 and Grade 2. The most common (>5%) treatment related hematologic adverse events of ≥ Grade 3 were neutropenia (15.1%), leukocytopenia (5.4%), lymphocytopenia (5.4%). The most common (>5%) treatment related non-hematologic adverse events of ≥ Grade 3 were pneumonia (15.1%).

Dr. Lugui Qiu, a prinicipal investigator on the study, stated "FL is complicated as the relapsed and refractory patients tend to progress rapidly, requiring aggressive therapies. From the clinical findings with linperlisib treatment of FL patients, we are seeing durable responses for most patients. Patients are in desperate need of effective therapies that target these lymphoma key signaling pathways and therapies that are oral medications, easy for patients to use outside of a clinic."

Dr. Zusheng Xu, General Manager of Yingli Pharma commented "We are excited to be developing Linperlisib for the treatment of lymphomas and solid tumors. Linperlisib is a next-generation PI3Kδ-selective inhibitor. The clinical data suggest that Linperlisib might be a potentially advantageous treatment option for patients. We have applied a linperlisib marketing approval in China in relapsed or refractory FL, based on the data from this phase II registration study. We hope to broaden the use of linperlisib and are exploring its anti-tumor activities in different indications in additional clinical trials."

Dr. Qiu also indicated "It is a major step that Linperlisib has been accepted by the NMPA for the NDA application, and we are very optimistic about the outcome."

About Linperlisib

Linperlisib (YY-20394) is a highly selective and potent PI3Kδ inhibitor that has shown a favorable safety profile, exciting anti-tumor activities, and good PK and pharmaceutical properties as an oral once-a-day agent in late-stage clinical development. A phase 1 clinical trial was completed in 2020 demonstrating linperlisib to be a safe and tolerable agent, and a recommended phase 2 dose of 80 mg QD was established. Linperlisib was awarded NMPA Breakthrough Therapy status in China, leading to the current trial. In addition, linperlisib received FDA Orphan Drug Designations for FL, CLL/SLL, and T cell lymphoma. A clinical trial in r/r FL is launching in the US. Multiple linperlisib clinical trials being conducted in other lymphomas, solid tumors, and in combination with gemcitabine/oxaliplatin in r/r DLBCL. Preliminary results from a PTCL Phase1b study were reported at ASCO (Free ASCO Whitepaper) 2021, indicating an overall response rate of 70% with 33% CRs in 30 evaluable patients with r/r PTCL, a difficult to treat and aggressive form of lymphoma.

On June 11, 2021 ImmVira reported that in the Phase II Clinical Trials of its leading oncolytic virus product, MVR-T3011* as intratumoral administration (MVR-T3011 IT), ImmVira has completed the first dosing in both China and the U.S. on May 28 2021 and June 11 2021, respectively (Press release, Immvira, JUN 11, 2021, View Source [SID1234583938]).

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MVR-T3011, ImmVira’s proprietary next-generation, genetically modified oncolytic herpes simplex virus ("oHSV"), is developed on a novel virus backbone design driven by ImmVira’s innovative insights in oncolytic viruses and superior gene recombinant technology. The incorporation of two exogenous genes, PD-1 antibody and IL-12, further enhances immune responses. MVR-T3011 is ImmVira’s first pipeline undergoing clinical trial and includes intratumoral administration of MVR-T3011. Phase I clinical trials commenced in China in April 2020 and commenced in the United States and Australia in September 2020. Data collected from these preliminary Phase I clinical studies have demonstrated a favorable safety profile and promising efficacy profile. No dose-limiting toxicities have been observed in participants.

The U.S. Phase IIa portion of the study consists of two parts: (i) MVR-T3011 as a single agent for melanoma and metastatic solid tumors; (ii) MVR-T3011 in combination with pembrolizumab for non-small-cell lung carcinoma. The China Phase IIa (MVR-T3011 as a single agent) study targets head and neck cancer, sarcoma and breast cancer. These multi-center studies cover various indications providing highly efficient and cost-effective clinical development strategy to rapidly advance clinical development for MVR-T3011 across regions.

"Leveraging the OvPENS new drug R&D platform, ImmVira is a pioneer in the field," said Dr. Grace Zhou, Chairwoman of the Board of ImmVira. "ImmVira will make best use of its long-term experience and creative insights in oncolytic virus to construct broader product pipelines and provide effective, innovative and safe single-agent as well as combined oncolytic virotherapies for the anti-tumor market." Professor Bernard Roizman has resigned from as Chairman of the Board in February 2020 due to personal health reason and he has not held any positions in ImmVira and its subsidiaries since then. Dr. Grace Zhou has been appointed as Chairwoman of the Board since February 2020.

* Note: MVR-T3011 is the pipeline designation representing T3011, the product code registered in the US and China for clinical trials.