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Yingli Pharma Announces a presentation on the Phase 2 clinical trial of linperlisib, a PI3Kδ selective inhibitor, in relapsed or refractory follicular lymphoma at the European Hematology Association 2021 Congress

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.

Ryvu Therapeutics Presents Positive Phase I Data for RVU120 at the Virtual 26th Annual Congress of the European Hematology Association. Phase I/II Data for SEL24 (MEN1703) presented by development partner Menarini

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.

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.

CEL-SCI Announces the Closing of $31.7 Million Bought Deal Offering

On June 11, 2021 CEL-SCI Corporation (NYSE American: CVM), a Phase 3 cancer immunotherapy company, reported the closing of the offering of 1,400,000 shares of its common stock at a price of $22.62 per share, for total gross proceeds of approximately $31.7 million, before deducting underwriting discounts and other offering expenses payable by the Company (Press release, Cel-Sci, JUN 11, 2021, View Source [SID1234583912]). Additionally, the Company has granted the underwriter a 30-day option to purchase up to 210,000 additional shares to cover over-allotments.

Kingswood Capital Markets, division of Benchmark Investments, LLC acted as sole book-running manager for the offering.

The shares of common stock described above were offered by CEL-SCI pursuant to a "shelf" registration statement on Form S-3 (File No. 333-226558) filed with the Securities and Exchange Commission (SEC) and the accompanying prospectus contained therein. The offering of the shares of common stock were made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A preliminary prospectus supplement and the accompanying prospectus relating to and describing the terms of the offering was filed with the SEC. A final prospectus supplement was also filed with the SEC. Copies of the preliminary prospectus supplement, final prospectus supplement and the accompanying prospectus relating to this offering may be obtained on the SEC’s website at View Source or by contacting Kingswood Capital Markets, Attention: Syndicate Desk, 590 Madison Avenue, 39th Floor, New York, NY 10022, by email at [email protected], or by telephone at (212) 404-7002.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Valemetostat Data at EHA Shows Promising Durable Tumor Response in Patients with Peripheral T-Cell Lymphoma and Adult T-Cell Leukemia/Lymphoma

On June 11, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that New data from for valemetostat, a potential first-in-class specific and potent dual inhibitor of EZH1 and EZH2, showed promising and durable tumor response in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) and adult T-cell leukemia/lymphoma (ATL).1,2 The data were reported today during an oral presentation (Abstract #S218) at the Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (#EHA2021) (Press release, Daiichi Sankyo, JUN 11, 2021, View Source [SID1234583911]).

PTCL is a group of rare and heterogenous malignancies, including ATL, which represent about 10-15% of all non-Hodgkin lymphomas (NHL).3 The majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen, and median overall survival following relapse is approximately 5.8 months.4 New innovative treatment strategies are needed to improve survival in these patients.

In this first-in-human phase 1 study of valemetostat in B-cell and T-cell NHL, data were reported at EHA (Free EHA Whitepaper) in the subset of patients with relapsed/refractory PTCL and ATL. The objective response rate (ORR), based on investigator’s assessment, was 54.5% (CI 95%: 38.8-69.6) in 44 patients with PTCL including 12 complete responses (CRs) and 12 partial responses (PRs). A median duration of response (DOR) of 56.00 weeks (CI 95%: 44.43-NE) and a median progression-free survival (PFS) of 52.00 weeks (CI 95%: 16.14-NE) were observed after a median follow-up of 19.93 weeks (range: 3.1-68.1).

The ORR in 14 patients with ATL was 57.1% (CI 95%: 28.9-82.3), with four CRs and four PRs. Median DOR and PFS were not estimable for patients with ATL after a median follow-up of 23.07 weeks (range: 3.3-125.0). Twelve patients with PTCL and six patients with ATL remained on treatment with valemetostat at the time of data cutoff on November 2, 2020.

The safety profile of valemetostat in patients with PTCL and ATL (n=58) was similar with that seen across all patients with NHL (n=77). Grade 3 or higher treatment emergent adverse events (TEAEs) occurred in 54 of 77 NHL patients (70.1%) and included neutrophil count decrease (23.4%), lymphocyte count decrease (22.1%), platelet count decrease (16.9%), white blood cell count decrease (15.6%), anemia (11.7%), diarrhea (1.3%) and alanine aminotransferase (ALT) increase (1.3%). Dose interruption or reductions due to TEAEs occurred in 41.6% (n=32) and 10.4% (n=8) of all patients with NHL, respectively.

"The proportion of patients who responded to valemetostat and the durability of responses observed in this trial are very encouraging for patients with PTCL, including ATL, which remains one of the most significant areas of unmet need in the treatment of hematologic cancers," said Shigeru Kusumoto, MD, Associate Professor, Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Japan. "Because both EZH1 and EZH2 play important roles for the pathophysiology of PTCL and ATL, dual targeting of EZH1 and EZH2 with valemetostat may be an innovative approach for these difficult-to-treat diseases."

"We are committed to translating the novel mechanism of valemetostat into a potential treatment option for patients with PTCL and ATL in various regions around the world where these types of blood cancers are most prevalent," said Ken Takeshita, MD, Global Head of Research and Development, Daiichi Sankyo. "Based on the promising clinical activity seen in this phase 1 study, we have initiated VALENTINE-PTCL01, a global pivotal study that will further evaluate the efficacy and safety of valemetostat in patients with relapsed or refractory PTCL including ATL."

Patients with PTCL enrolled in the study had received a median of two prior treatments (range: 1-8), including prior hematopoietic stem cell transplantation (HSCT; 20.5%). Patients with ATL had received a median of two prior treatments (range: 1-8), including HSCT (14.3%).

Summary of Phase 1 Results

Efficacy Measure

Valemetostat Phase 1 Dose Expansion 200 mg (n=58)

PTCLiii, iv (n=44)

ATLv,vi (n=14)

ORR (%) (95% CI) i,ii

54.5% (38.8-69.6)

57.1% (28.9-82.3)

12 (27.3)

4 (28.6)

12 (27.3)

4 (28.6)

5 (11.4)

2 (14.3)

8 (18.2)

3 (21.4)

1 (2.3)

0 (0)

Not done

6 (13.6)

1 (7.1)

Time to response (weeks)

8.14 weeks (4.1-24.1)

8.14 weeks (7.3-84.1)

Median DOR (weeks) (95% CI)

56.00 weeks (44.43-NE)

NE (6.14-NE)

Median PFS (weeks) (95% CI)

52.00 weeks (16.14-NE)

NE (8.14-NE)

Abbreviations: ORR, objective response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NE, not evaluable; DOR, duration of response; PFS, progression-free survival
i As assessed by investigator
ii ORR is CR+PR (including uncertified CR [CRu] for ATL)
iii Includes PTCL subtypes: AITL (angioimmunoblastic T-cell lymphoma), PTCL-NOS (not otherwise specified), ALCL (anaplastic large cell lymphoma) and "other" PTCL
iv Median follow-up: 19.93 weeks (range: 3.1-68.1)
v Includes 7 patients with acute and 7 patients with lymphomatous ATL subtypes
vi Median follow-up: 23.07 weeks (range: 3.3-125.0)

About the Phase 1 Study

The open-label, single-arm, multi-center, first-in-human, two-part phase 1 study is evaluating the safety and efficacy of valemetostat in adult patients with relapsed/refractory NHL, including B-cell and T-cell lymphomas. Following the dose escalation portion of the study, which evaluated safety, pharmacokinetics and determined the recommended dose for expansion (200 mg once daily), the dose expansion part enrolled patients into one of two cohorts based on NHL subtype (PTCL and ATL) to further evaluate safety and assess preliminary efficacy. For more information about this study, visit ClinicalTrials.gov.

About VALENTINE-PTCL01 Trial

Data from the phase 1 study of valemetostat presented at EHA (Free EHA Whitepaper) informed the design of the recently initiated pivotal VALENTINE-PTCL01 study. A global, open-label, single-arm, two-cohort phase 2 study, VALENTINE-PTCL01 is evaluating the efficacy and safety of valemetostat in patients with relapsed/refractory PTCL and ATL who have received at least one systemic therapy and are ineligible for HSCT. The first cohort will enroll patients with PTCL, and a second cohort will enroll patients with ATL.

The primary efficacy endpoint of the study is ORR according to blinded independent central review. Secondary efficacy endpoints include CR, PR, DOR, PFS and overall survival. The study will analyze safety endpoints including adverse events as well as pharmacokinetic and exploratory biomarker endpoints. Up to 176 patients will be enrolled at approximately 70 sites in Asia, Europe, North America and Oceania. For more information about this study, visit ClinicalTrials.gov.

About PTCL and ATL

PTCL is a group of rare and heterogenous hematologic malignancies, including ATL, that represent approximately 10-15% of all NHLs.3 Approximately 544,000 new cases of NHL were diagnosed worldwide in 2020.5 There are at least 29 recognized subtypes of PTCL, which occur with significant geographic variation.6 The most common subtypes of PTCL occur frequently in Western countries and in Asia, while ATL is generally more frequent in Japan and parts of the Caribbean and Latin America.7 ATL is associated with the human T-cell lymphotropic virus type 1 (HTLV-1).8

PTCL tends to be aggressive and prognosis is generally poor, with five-year overall survival at 32% in two common PTCLs (PTCL-NOS and AITL) and at 14% for ATL.7 Initial treatment for PTCL is typically a multi-drug chemotherapy-based regimen, and a majority of patients progress with median overall survival of 5.8 months from time of relapse.4 Development of more effective medicines for PTCL and ATL continues to be an unmet clinical need, and one newer area of research and development includes therapeutic targeting of epigenetic changes that contribute to lymphomagenesis.8

About EZH1 and EZH2

EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes are part of polycomb protein complexes and act through histone methylation to regulate expression of genes involved in maintaining hematopoietic stem cells.9 These enzymes are thought to contribute to silencing of genes that suppress tumor cell growth and proliferation.10 EZH1 and EZH2 are recurrently highly expressed or mutated in many hematologic malignancies.10 Research shows that both EZH1 and EZH2 enzymes have a role in hematologic cancer progression and that simultaneous inhibition would be effective in targeting the cancers.1 There are no dual EZH1/2 directed therapies approved for cancer treatment.

About Valemetostat

Valemetostat (DS-3201) is a potential first-in-class, potent and selective small molecule EZH1/2 dual inhibitor currently in clinical development in the Alpha portfolio of Daiichi Sankyo. Valemetostat targets epigenetic regulation by inhibiting both the EZH1 and EZH2 enzymes.

The valemetostat development program includes VALENTINE-PTCL01, a global pivotal phase 2 trial in patients with relapsed/refractory PTCL and ATL; a pivotal phase 2 trial in patients with relapsed or refractory ATL in Japan; a phase 1 study in patients with relapsed/refractory NHL in the U.S. and Japan; and, a phase 1 study in patients with acute lymphocytic leukemia and acute myeloid leukemia in the U.S.

In April 2019, valemetostat received SAKIGAKE Designation for the treatment of adult patients with relapsed or refractory PTCL by the Japan Ministry of Health, Labour and Welfare (MHLW).

Valemetostat is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.

Kyowa Kirin welcomes the decision that NICE will revisit their appraisal of the innovative systemic treatment, POTELIGEO®▼ (mogamulizumab), for adults living with two forms of ultra-rare non-Hodgkin lymphoma

On June 11, 2021 Kyowa Kirin reported that The National Institute for Health and Care Excellence (NICE) has upheld an appeal lodged by Kyowa Kirin, Lymphoma Action and Leukaemia Care, and the UK Cutaneous Lymphoma Group (UKCLG) as part of the Single Technology Appraisal for POTELIGEO (mogamulizumab) for the treatment of adults with the ultra-rare blood cancers mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy (Press release, Kyowa Hakko Kirin, JUN 11, 2021, View Source [SID1234583910]).1

The oral appeal hearing took place on 10 May 2021 in front of an independent Appeal Panel appointed by NICE. The Panel heard arguments from representatives of the appellants against the decision not to recommend POTELIGEO, as published in a Final Appraisal Document (FAD) on 4 March 2021.2

The parties involved in the appeal welcome this decision as it represents a significant and positive step forward for the cutaneous T-cell lymphoma (CTCL) community, where there is a high clinical unmet need. Kyowa Kirin remains committed to finding a solution for people living with SS or MF to have access to POTELIGEO and will continue discussions with NICE and NHS England to find a resolution.

Richard Johnson, Northern Cluster General Manager, responsible for the UK at Kyowa Kirin, commented: "The outcome of this appeal is an important step in enabling access to an innovative treatment for people with MF or SS who have few systemic treatment options. We remain committed to working with the patient and clinical community, as appropriate, and we are optimistic that future reconsideration of evidence by the Committee, could resolve the challenges with this appraisal. We strongly believe in the clinical and cost effectiveness of POTELIGEO and will continue a dialogue with NICE and NHS England."

MF and SS are two forms of CTCL3 which is a serious and potentially life-threatening form of cancer.4 Additionally, there is a significant impact on quality of life for those caring for an individual living with CTCL.5 CTCL is treatable but not curable and there is a clear unmet need for new treatment options.

Ropinder Gill, Chief Executive at Lymphoma Action commented: "We’re very grateful and pleased that the NICE Appeal Panel upheld the appeal around mogamulizumab on a number of grounds. This means that by relooking at aspects such as mogamulizumab’s cost effectiveness, there is an opportunity to make this treatment available to those people affected by skin lymphoma who have limited treatment options left. We are hopeful that NICE’s reassessment might bring parity with the SMC’s decision to make mogamulizumab available in Scotland."

About POTELIGEO (mogamulizumab)

Mogamulizumab is a first-in-class humanised monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), a protein consistently expressed on cancerous cells seen in both MF and SS;6,7,8 once mogamulizumab binds to CCR4, it increases attraction of immune cells from the immune system to destroy the cancerous cells.9

Mogamulizumab has been shown to offer benefits to many patients with MF and SS.10 The MAVORIC trial compared the efficacy of mogamulizumab with vorinostat in previously treated people with relapsed or refractory mycosis fungoides or Sézary syndrome, two types of Cutaneous T-cell lymphoma (CTCL).10 Patients taking mogamulizumab experienced control over their disease for more than twice as long as those taking the comparator treatment, vorinostat*1 (7.7 months vs 3.1 months of median progression free survival), the primary endpoint of the trial.10 Levels of adverse events were similar between the two treatment groups.10 The MAVORIC trial is the largest in CTCL; it enrolled a total of 372 patients across 61 sites in 11 countries (of which 16 sites were in Europe, including three in England).10

About Mycosis Fungoides (MF) and Sézary Syndrome (SS)

MF and SS are characterised by localisation of cancerous white blood cells called T lymphocytes (T cells), to the skin.11,12 These cancerous T cells consistently express a protein called CC-chemokine receptor 4 (CCR4), which enables them to move from the blood to the skin.6,7,8 When these cancerous T cells move to the skin, they can create a localised inflammatory immune skin response, commonly resulting in visible skin symptoms of red patches or plaques 6,13,14,15,16 which can resemble psoriasis or eczema.11

MF and SS can affect the skin, blood, lymph nodes (part of the body’s immune system which is spread throughout the body) and internal organs.17 All four areas of the body are used to assess disease stage,18,19 and clinically significant involvement of the blood, particularly in more advanced disease, is linked with increased morbidity and an overall reduction in patient survival.18,20,21

CTCL can take, on average, between 2 and 7 years for individuals to receive a confirmed diagnosis.22 It is critical for doctors to consider CTCL as an early differential diagnosis as the patient’s prognosis can be affected if the disease progresses to later stages.23 Whilst most individuals that present with early stage disease do not progress to a more severe stage,24 patients with advanced disease have significantly poorer outcomes with only around half of patients (52%) surviving for just 5 years.18

CTCL is a ultra-rare disease that affects 0.7 per 100,000 patients across the UK.25 The annual incidence of MF in Europe is estimated to be between 1 in 110,000 to 1 in 350,000.26 The annual incidence of SS is 1 in 10,000,000.27 Together they represent approximately 65% of all cases of CTCL.17