On June 7, 2023 Real-world data and expert perspectives on state-of-the-art clinical practice for the management of infection in patients with CLL will be showcased during the Octapharma Update-in-Hematology session at the EHA (Free EHA Whitepaper) Hybrid Congress on June 9, 2023, in Frankfurt, Germany (Press release, Octapharma, JUN 7, 2023, View Source [SID1234632574]).

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Secondary immunodeficiency (SID) is a common complication in patients with haematological malignancies such as CLL. Up to 85% of patients with CLL develop hypogammaglobulinemia, either due to the underlying disease or as a side effect of treatment.1 Patients with hypogammaglobulinemia are more likely to develop infections, which are a major cause of morbidity and account for up to 60% of deaths in patients with CLL.2 The use of immunoglobulin therapy (intravenous and subcutaneous) is well established as secondary prophylaxis once patients experience a severe/repeated infection. Furthermore, primary prophylaxis with immunoglobulin therapy has been suggested to decrease infection rates but more robust data are needed to evaluate the safety and efficacy of this strategy.3-5

Octapharma’s interactive Update-in-Hematology session "Chronic Lymphocytic Leukemia (CLL) and Beyond: Management of the Infection Burden" will begin with a spotlight on the risk of infections in patients with CLL using a data-driven and machine learning approach by Dr Caspar da Cunha-Bang, Rigshospitalet, Copenhagen, Denmark. This will be followed by a discussion on the risk factors for infections and the importance of guideline recommendations in choosing the right treatment to reduce the severity of these infections by Professor Hartmut Link, Haematology Oncology Kaiserslautern, Kaiserslautern, Germany. Finally, Professor Livio Trentin, University of Padua, Italy, will speak about his experience using subcutaneous immunoglobulin therapy for infection prophylaxis in patients with CLL. In addition, he will share his first-hand experience with ongoing research into this area, including the PRO-SID clinical trial and its potential for primary infection prophylaxis. The session will round off with an exciting panel discussion bringing together the audience and experts to exchange views on challenging cases of infections associated with CLL.

Stephan Stilgenbauer, Professor of Medicine and Medical Director of the Comprehensive Cancer Centre in Ulm, Germany, will chair the session. He stated, "The COVID-19 pandemic has vividly reminded us about the impact of infections on patients. Therefore, novel perspectives in approaching prophylaxis in CLL are highly valued – I am very much looking forward to discussing some of these exciting advances in the field with the international panel of speakers and audience at this session."

Octapharma has a longstanding commitment to improving the management of patients with SID, and in 2020 launched PRO-SID (NCT04502030), a Phase III clinical trial investigating primary infection prophylaxis with panzyga, a human immunoglobulin for intravenous administration, in patients with CLL and SID. Over 240 adult patients with CLL and hypogammaglobulinemia (IgG levels < 5 g/L) who are receiving antineoplastic treatment will be enrolled to investigate the efficacy and safety of panzyga compared with placebo. The primary outcome is the occurrence of at least one major infection over 52 weeks. With this trial, Octapharma aims to gather robust clinical data on the efficacy of primary prophylaxis in managing infection risk in patients with SID and expand the treatment options in these patients.

Livio Trentin, Professor of Haematology and Director of the Haematology Unit at Padua University, is supervising one site of the PRO-SID trial. He commented: "There remains a significant need to establish the most effective approach to managing patients with haematological malignancies and secondary immunodeficiency. Proactive management of infections in these patients using primary prophylaxis with intravenous immunoglobulin has great potential but it is important that we gather robust evidence on the efficacy and safety of this treatment option through trials such as PRO-SID."

Olaf Walter, Board Member at Octapharma, added: "Octapharma is delighted to support this Update-in-Hematology session, and we look forward to facilitating expert perspectives and audience interaction to improve the care of patients with CLL. We are also proud to support the PRO-SID study which will provide important data to understand how to improve and potentially save the lives of these patients."

In addition to this Update-in-Hematology session, the strong commitment of Octapharma to the field of SID will be illustrated by the presentation of a subgroup analysis of patients with SID in a non-interventional safety study conducted in Germany. The results of this analysis on 3,846 SID patients will be displayed and commented during the poster session of the Congress on June 9, 2023:

P1505: "Tolerability and safety of intravenous immunoglobulins (5% and 10%) for the treatment of patients with secondary immunodeficiencies – Final subgroup results of a non-interventional safety study," presented by Octapharma.
We look forward to seeing you soon at EHA (Free EHA Whitepaper) 2023 – drop by the Octapharma booth on-site in Frankfurt for more information.

About panzyga

Panzyga is a 10% human normal immunoglobulin solution ready for intravenous administration. Panzyga is approved for use in treatment of primary immunodeficiency, idiopathic thrombocytopenic purpura (ITP) and chronic inflammatory demyelinating polyneuropathy (CIDP) in the USA, Europe and Canada. It is also approved for secondary immunodeficiencies and Guillain Barré syndrome in Europe and Canada and for Kawasaki disease, and multifocal motor neuropathy (MMN) in Europe.

On June 7, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA) reported its second broad provisional patent application covering the composition of matter for a new telomere-targeting molecule (Press release, MAIA Biotechnology, JUN 7, 2023, View Source [SID1234632573]). MAIA is creating and evaluating multiple telomere-targeting compounds designed to modify the telomeric structure through the cancer cell – intrinsic telomerase activity – and thus cause the death of these cells. The studies, conducted in vitro in multiple cancer cell lines and in vivo in several pre-clinical cancer models, demonstrated the intended mechanism of action and high-level anti-cancer activity for these new molecules.

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MAIA has nominated a new molecular entity candidate (designated as MAIA-2021- 029) for further advancement into preclinical GLP-toxicity and other studies, and may advance this candidate into human clinical trials upon completion of the required preclinical evaluations. The patent titled "TUMOR REDOX-ACTIVATED 6-THIOPURINE CONTAINING DIMER COMPOUNDS" further adds to MAIA’s Telomere-Targeting Molecule Program, which includes THIO, the lead therapeutic candidate currently being evaluated in a Phase 2 clinical trial, and follow-on compounds MAIA-2021-020 and MAIA-2022-012, patented in the fourth quarter of 2022.

"The discovery and preclinical advancements of these new telomere-targeting compounds represent another significant chapter for MAIA. We have observed impressive single-agent activity in several different tumor types for the new candidates, as well as in combination with immune checkpoint inhibitors," said Sergei Gryaznov, Ph.D., MAIA Chief Scientific Officer. "The observed anti-cancer activity in vitro and in vivo is quite remarkable, often leading to complete tumor eliminations. We are working diligently to advance these candidates toward clinical development."

"The development of proprietary new molecular entity candidates is a key component to MAIA’s strategy and greatly increases the chances to bring a highly efficacious telomere-targeting therapy to market. Our molecules can be used in the treatment of multiple cancer indications, and with the excellent preliminary results observed in our ongoing Phase II trial evaluating THIO in patients with Non-Small Cell Lung Cancer, we look forward to announcing further developments of MAIA’s proprietary new molecular entity candidates," said MAIA Chairman and Chief Executive Officer Vlad Vitoc, M.D.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is an investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

On June 7, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported initial proof of concept monotherapy data from its Phase 1 MYTHIC clinical trial evaluating lunresertib (RP-6306), a first-in-class, oral PKMYT1 inhibitor in molecularly selected advanced solid tumors (Press release, Repare Therapeutics, JUN 7, 2023, View Source [SID1234632572]).

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"These initial proof of concept results for lunresertib monotherapy show a favorable and distinct tolerability profile and preliminary antitumor activity that support our development plans for this program," said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "The data demonstrate that lunresertib effectively inhibits PKMYT1 and offers a synthetic lethal combination with CCNE1 amplification or inactivating mutations in FBXW7 and PPP2R1a. These genetic alterations have previously been considered undruggable and represent a significant unmet medical need. These findings, along with the continued advancement of the lunresertib program across multiple ongoing combination clinical trials, validate our proprietary STEP2 platform and precision medicine approach."

"While early, these promising proof-of-concept data continue to support our belief in the potential transformative role that lunresertib could play, either alone or in combination with other therapies, in patients with molecularly selected advanced solid tumors," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "We look forward to reporting initial combination data of lunresertib with camonsertib, as well as lunresertib with gemcitabine, in the fourth quarter of this year, while also advancing multiple other trials to further our understanding of our first-in-class PKMYT1 inhibitor program."

Key Initial Findings from the Phase 1 MYTHIC Clinical Trial:

MYTHIC (NCT04855656) Module 1 is a first-in-human, global, open-label Phase 1 dose-escalation study to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of a novel and potent small molecule PKMYT1 inhibitor, lunresertib. MYTHIC Module 2 will investigate lunresertib in combination with camonsertib (RP-3500/RG6526), a potent and selective oral inhibitor of ATR developed by Repare and now partnered with Roche (excluding the lunresertib combination), in molecularly selected advanced solid tumors. As of the data cutoff date of April 28, 2023, 63 patients were enrolled in lunresertib monotherapy Module 1 of the MYTHIC study, which is ongoing and accruing patients.

Tolerability profile of lunresertib monotherapy appears favorable and differentiated from other clinical cell cycle inhibitors, which have been characterized with myelotoxicity and diarrhea. No grade 4 toxicity was observed with lunresertib, where grade 3 treatment emergent adverse events of interest included rash (7.9%), anemia (6.3%) and nausea or vomiting (1.6%) The only dose limiting toxicity was reversible rash, alleviated with dose modifications and simple supportive measures.
Two recommended dose/schedules were identified – 240mg daily continuously and 80-100mg BID intermittent weekly – to offer maximum flexibility in combination studies.
Pharmacodynamic analysis confirmed lunresertib treatment results in PKMYT1 target inhibition at active doses and increases DNA damage.
Preliminary anti-tumor activity was observed, including moderate tumor shrinkages and a confirmed partial response per RECIST 1.1 criteria. Several patients demonstrated long stable disease and remain on treatment for greater than 11 months and ongoing.
Early clinical combination insights demonstrated greater anti-tumor activity in patients treated with the combination of lunresertib and camonsertib than lunresertib alone, based on higher molecular response rates and RECIST 1.1 responses. Examples of confirmed partial responses are provided for the three tested sensitivity genotypes in endometrial adenocarcinoma, cholangiocarcinoma and colorectal cancer, with more details planned for the Q4 scientific presentation.
Encouraging early responses observed across gemcitabine, camonsertib, and FOLFIRI clinical combinations in multiple tumor types and genotypes.
Favorable and distinct tolerability profile and preliminary antitumor activity demonstrated thus far support potential development plans that may include further trials of lunresertib in various combination and maintenance approaches.
Repare is also currently evaluating lunresertib in combination with gemcitabine in the Phase 1 MAGNETIC study and in combination with FOLFIRI in the Phase 1 MINOTAUR study. Repare is working with Princess Margaret Cancer Center to initiate clinical testing, as part of an investigator-sponsored trial (IST), of a fourth lunresertib combination with carboplatin and paclitaxel for the treatment of recurrent TP53 mutated ovarian and uterine cancer, with first patient dosing expected this year. The Company is also collaborating with the Canadian Cancer Trials Group in an ongoing basket Phase 2 IST that is enrolling patients with selected, advanced cancers receiving lunresertib as combination (NCT05605509), and in a second active study that will evaluate lunresertib in combination with gemcitabine in patients with CDK4/6 inhibitor treated ER+/HER2- metastatic breast cancer (NCT05601440). These studies aim to expand the treatment opportunities for lunresertib to earlier stages of cancer treatment or additional tumor types.

Company Virtual Webcast Event:

The Company will host a virtual investor webcast with accompanying slides for analysts and investors today at 4:30 p.m. Eastern Time to further discuss the lunresertib program, including initial proof-of-concept monotherapy data from MYTHIC and an update on ongoing combination clinical trials.

To access the call, please dial (877) 870-4263 (U.S. and Canada) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live video webcast will be available in the Investor section of the Company’s website at View Source A webcast replay will also be archived for at least 30 days.

On June 7, 2023 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage oncology company dedicated to the discovery and development of novel biotherapeutics by targeting inhibitory receptors on myeloid cells, reported Phase 1 data for IO-202, a first-in-class humanized IgG1 monoclonal antibody targeting Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4, also known as ILT3) (Press release, Immune-Onc Therapeutics, JUN 7, 2023, View Source [SID1234632571]). Data from the dose escalation part of the Phase 1 study evaluating patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) will be presented during a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Frankfurt, Germany on June 9, 2023.

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"AML is the most common form of acute leukemia in adults in the U.S. and is characterized by high rates of relapsed and refractory disease. Monocytic AML is especially in need of break-through medicine as it is often resistant to standard-of-care treatment. CMML is a rare leukemia overlap syndrome characterized by the accumulation of monocytes in the blood and bone marrow, with both myeloproliferative and myelodysplastic features," said IO-202 Phase 1 investigator, Courtney DiNardo, M.D., MSCE, associate professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX. "These results, showing strong safety and promising clinical activity as both monotherapy and in combination with a standard-of-care chemotherapy for monocytic AML and CMML, suggest that LILRB4 may be an important therapeutic target for hard-to-treat blood cancers."

"We are very encouraged with the efficacy data of IO-202 as a single agent and in combination with azacitidine in heavily pre-treated patients with R/R AML and CMML," said Paul Woodard, MD, chief medical officer of Immune-Onc. "Based on the data, we have developed a patient enrichment strategy for the ongoing dose expansion phase of the study to select AML patients who would most likely respond to IO-202. We are also pleased to receive the FDA Fast Track designation for IO-202 for the treatment of R/R CMML, which follows the R/R AML Fast Track designation received in 2022. We look forward to working closely with the FDA and trial investigators to accelerate the clinical development of IO-202 in hematologic malignancies."

The Phase 1 multicenter, open-label, dose escalation study of IO-202 assessed the safety and tolerability of IO-202 in successive cohorts of patients with R/R AML with monocytic differentiation and R/R CMML as its primary objective. Secondary and exploratory objectives included pharmacokinetics, immunogenicity, pharmacodynamic (PD) biomarker effects, and clinical response rate of IO-202 as a monotherapy and in combination with azacitidine (AZA).

Treatment with IO-202 was well tolerated. There were no dose-limiting toxicities observed and a maximum tolerated dose was not reached. In the monotherapy treatment cohorts, one CMML patient demonstrated clinical benefit for more than one year and one AML patient achieved a partial response (PR). In combination therapy cohorts, Complete Remission (CR) has been achieved and is on-going for over 10 months in an AML patient with high LILRB4 expression. Additionally, 3 out of 5 CMML patients achieved clinical benefit including Optimal Marrow Response.

Based on the promising results of the dose escalation part of the study and utilizing a biomarker driven patient selection strategy, the Company has opened dose expansion cohorts to enroll AML patients with monocytic differentiations and high LILRB4, and CMML patients (IO-202-CL-001; NCT04372433).

Poster presentation details are as follows:

Abstract Number: P536
Title: A first-in-human Phase 1 study of IO-202 (anti-LILRB4 mAb) in Acute Myeloid Leukemia (AML) with monocytic differentiations and Chronic Myelomonocytic Leukemia (CMML) patients.
Presenter: Courtney DiNardo, M.D., MSCE, Associate Professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX
Session Title: Acute myeloid leukemia – Clinical
Session Date and Time: Friday, June 9, 6:00 p.m. – 7:00 p.m. CEST

Abstracts and full session details can be accessed through the EHA (Free EHA Whitepaper) Online Program Planner

ABOUT IO-202

IO-202 is a humanized IgG1 monoclonal antibody (mAb) with high affinity and specificity towards LILRB4 (also known as ILT3). It blocks the interaction of LILRB4 with multiple ligands, including ApoE and Fibronectin, and has broad potential in blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 causes depletion of cells expressing high LILRB4 through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In the context of solid tumors, preclinical data presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting demonstrate that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in an immune competent model in vivo.

IO-202 has two ongoing clinical studies in the U.S.: The Phase 1 trial is currently enrolling expansion cohorts of patients with monocytic (LILRB4 high) acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML) in combination with standard-of-care agents such as azacitidine +/- venetoclax (NCT04372433). The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020, as well as Fast Track designations for relapsed or refractory AML in 2022 and relapsed or refractory CMML in 2023. The second Phase 1 trial of IO-202 is currently enrolling patients with advanced solid tumors to evaluate IO-202 as a monotherapy and in combination with an anti-PD-1 (NCT05309187).

On June 7, 2023 Dizal (688192.SH ) reported compelling data of its robust oncology portfolio at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 2-6, 2023, in Chicago (Press release, Dizal Pharma, JUN 7, 2023, View Source [SID1234632570]). Highlights include new or updated findings from Dizal’s leading assets sunvozertinib (a selective EGFR TKI targeting a wide spectrum of EGFR mutations) and golidocitinib (a JAK1 only inhibitor), which have demonstrated superior efficacy in treating advanced non-small cell lung cancer (NSCLC) and relapsed and refractory peripheral T-cell lymphoma (r/r PTCL), respectively.

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Sunvozertinib cemented "Best-in-Class" position for NSCLC patients with EGFR Exon20ins mutations

NSCLC patients with EGFR Exon20 insertion (Exon20ins) mutations have worse clinical outcomes due to the absence of effective targeted therapies. Sunvozertinib is a rationally designed, orally available, best-in-class tyrosine kinase inhibitor (TKI) that specifically targets these mutations. Its new drug application (NDA) has been accepted by the China National Medical Products Administration (NMPA) and granted priority review for the treatment of advanced NSCLC with EGFR Exon20ins mutations following platinum-based chemotherapies.

With longer follow-up, sunvozertinib showed an unprecedented ORR of 60.8% in the second-line setting and beyond

Updated results of WU-KONG6, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR Exon20ins mutations, were presented in an oral session. With longer follow-up, patients treated with sunvozertinib achieved a confirmed objective response rate (cORR) of 60.8% assessed by independent review committee (IRC). Anti-tumor efficacy was observed across a broad range of EGFR Exon20ins subtypes, and tumor response was also observed in patients with pretreated and stable brain metastasis.

Commenting on the findings, Prof. Mengzhao Wang, MD, PhD at Peking Union Medical College Hospital, the leading principal investigator of WU-KONG6, said, "Currently, only two new drugs have been approved in the US for≥2L treatment of EGFR Exon20ins NSCLC. However, their efficacy, particularly in terms of ORR, is significantly inferior to that of EGFR TKIs for EGFR sensitizing mutations. Nevertheless, WU-KONG6 study revealed that sunvozertinib had an impressive increase in ORR, reaching 60.8% in the ≥ second-line treatment of EGFR Exon20ins NSCLC. Additionally, sunvozertinib also demonstrated a high ORR regardless of mutation subtypes and insertion locations, as well as in patients with pre-treated and stable brain metastasis. These findings provide promising evidence for the treatment of EGFR Exon20ins NSCLC, and we are optimistic about sunvozertinib’s potential in a broader realm of NSCLC."

Sunvozertinib showed the "Best-in-Class" potential with an ORR of 77.8% in the first-line setting

According to the pooled analysis from WU-KONG1 part A and WU-KONG15, sunvozertinib monotherapy demonstrated significant efficacy in the treatment-naive EGFR Exon20ins NSCLC patients, achieving a best objective response rate (BOR) of 77.8% in the 300 mg cohort.

"EGFR Exon20ins is a primary resistant mutation, and there are currently no effective targeted therapies available for the first-line treatment. However, sunvozertinib demonstrated impressive efficacy in the ≥ second-line treatment of EGFR Exon20ins NSCLC, indicating its potential to become a superior therapeutic option in this area. Additional research is warranted to further explore its potential in the frontline." said Prof. Yan Xu, MD, PhD at Peking Union Medical College Hospital, the principal investigator of WU-KONG15, "The ASCO (Free ASCO Whitepaper) data revealed that sunvozertinib had an ORR of 77.8% in treatment-naive patients at the recommended Phase 2 dose (RP2D) of 300mg QD, exceeding the ORR of 71.2% observed with gefitinib in the IPASS study for treatment-naive patients with EGFR sensitizing mutations. A global multicenter, randomized phase III study (WU-KONG28) is ongoing to evaluate the efficacy and safety of sunvozertinib as a first-line treatment for NSCLC with EGFR Exon20ins mutations as compared to platinum-based doublet chemotherapy. We look forward to additional data readouts to strengthen the position of sunvozertinib in the EGFR Exon20ins domain."

In addition to expressive antitumor efficacies, sunvozertinib continues showing favorable overall safety profile, similar to other EGFR-TKIs. With its superior efficacy and manageable safety profile, sunvozertinib is poised to become a robust player in the realm of EGFR Exon20ins mutations.

Sunvozertinib showed encouraging anti-tumor efficacy in advanced NSCLC patients after failure of EGFR TKI treatment

While EGFR-targeted therapy can provide a durable survival benefit to NSCLC patients with EGFR mutations, resistance invariably emerges to current generation EGFR inhibitors.

Findings of the pooled analysis from WU-KONG1 Part A, WU-KONG2 and WU-KONG15 revealed that sunvozertinib exhibited encouraging anti-tumor efficacy in NSCLC patients with common EGFR mutations who failed standard EGFR TKI treatment.

A total of 37 heavily pretreated (median 5 lines of prior treatment) patients were treated with sunvozertinib, among whom 70.3% had previously received third-generation EGFR TKI, 91.9% received chemotherapy and 40.5% had baseline brain metastasis. At the data cut-off date of April 3, 2023, the median progression-free survival (mPFS) was 5.8 months, and the median duration of response (mDoR) was 6.5 months. And the safety profile was consistent with previous reports.

"Preclinical studies revealed that sunvozertinib showed potent antitumor activity against EGFR Exon20ins as well as EGFR sensitizing, T790M and uncommon mutations. It is worth noting that in patients with EGFR sensitizing mutations who had failed multiple lines of treatment, sunvozertinib monotherapy achieved a mPFS of 5.8 months, which is comparable to the efficacy of second-line chemotherapy." said Prof. James Chih-Hsin Yang, MD, PhD at National Taiwan University Hospital and National Taiwan University Cancer Center, the leading principal investigator of WU-KONG1, "According to the retrospective studies, re-challenge with EGFR TKIs may be a viable approach. In other words, re-administering EGFR TKIs after chemotherapy may help to overcome resistance that developed during previous EGFR TKI treatment. As chemotherapy and EGFR TKI may target different cell populations, switching to a different EGFR TKI could expand the treatment options for patients who are resistant to existing therapies. Further investigation is warranted to explore the potential of sunvozertinib in this area."

WU-KONG studies refer to clinical trials with sunvozertinib being conducted both as monotherapy and as combination therapy in NSCLC including WU-KONG1, WU-KONG2, WU-KONG6, WU-KONG15, WU-KONG21, and WU-KONG28 etc.

Golidocitinib yielded promising tumor responses in r/r PTCL

Relapsed or refractory peripheral T-cell lymphoma (r/r PTCL) is an aggressive non-Hodgkin lymphoma with a five-year survival rate of less than 30%. Currently there is no consensus on the standard treatment for r/r PTCL. New innovative treatment strategies are needed to improve survival in this patient population.

Dizal identified that JAK/STAT may mediate the pathogenesis of PTCL and launched clinical studies of golidocitinib to test the hypothesis. Golidocitinib is the First-in-Class Janus kinase 1 (JAK1) only inhibitor currently being evaluated in a multinational, pivotal study in r/r PTCL (JACKPOT8 Part B). Consistent with earlier data, golidocitinib demonstrated potent and durable anti-tumor efficacy in the pivotal study, with the presentation of clinical data delivered orally at 2023 ASCO (Free ASCO Whitepaper).

A total of 112 r/r PTCL patients were included in the analysis. IRC assessed ORR was 44.3% in 88 patients with PTCL including 21 complete responses (CRR, 23.9%). Anti-tumor efficacy was observed across different PTCL subtypes. The mDoR has not been reached. The longest DoR was 16.8 months, and the patient is still responding.

The safety profile of golidocitinib was benign. The majority of treatment-related adverse events (TRAEs) were hematological in nature and amenable to monitoring and management in the clinical setting. The median relative dose intensity was 100%, and the longest treatment duration was 18 months.

"Patients with r/r PTCL have limited treatment options and a poor prognosis. Golidocitinib has demonstrated superior efficacy compared to current treatment options for r/r PTCL, with an ORR of 44.3% and a complete response rate of 23.9%. These findings validate earlier research results and suggest golidocitinib as a potential therapeutic option to improve patients’ survival outcomes." said Qingqing Cai, MD, PhD at Sun Yat-sen University Cancer Center, the principal investigator of JACKPOT8, "Moreover, the favorable safety profile of golidocitinib suggests that highly selective JAK1 inhibitors may address the limitations of non-selective inhibition of JAK/STAT signaling pathway, thus offering a novel and effective targeted approach for treating PTCL."

Golidocitinib was granted Fast Track Designation by the US FDA in 2022. With promising efficacy and favorable safety profile, golidocitinib could be an innovative approach for this difficult-to-treat disease.

"The data presented at 2023 ASCO (Free ASCO Whitepaper) demonstrated the differentiation of our pipeline." said Xiaolin Zhang, PhD, Chairman and CEO of Dizal, "At Dizal, our focus is on advancing scientific research and development to deliver innovative drugs that can effectively address unmet medical needs and improve patient outcomes worldwide."

About sunvozertinib (DZD9008)

Sunvozertinib was designed with the goal to address the limitations of existing NSCLC therapies. It is a rationally designed, irreversible EGFR inhibitor targeting various EGFR mutations with wild-type EGFR selectivity. The first pivotal study WU-KONG6 of sunvozertinib has achieved its primary objective, demonstrating superior anti-tumor efficacy in pretreated NSCLC patients with EGFR Exon20ins. In January 2023, the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) granted priority review status to sunvozertinib and accepted the New Drug Application (NDA) for sunvozertinib for the treatment of advanced NSCLC with EGFR Exon20ins mutations after platinum-based chemotherapies. The confirmed objective response rate (cORR) at 300 mg was 60.8% assessed by IRC (Data cut-off date: October 17, 2022). Anti-tumor efficacy was observed across a broad range of EGFR Exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 Exon20ins mutations.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. Two multinational pivotal studies are ongoing in ≥ 2nd line (WU-KONG1) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR Exon20ins mutations.

Pre-clinical and Phase 1 clinical results of sunvozertinib were published in peer-reviewed journal Cancer Discovery (IF:39.397) in April 2022. The China NMPA has accepted NDA filing and granted priority review for sunvozertinib for the treatment of advanced NSCLC with EGFR Exon20ins mutations after platinum-based chemotherapy.

About Golidocitinib (DZD4205)

Golidocitinib is the first-in-class Janus kinase 1 (JAK1) only inhibitor currently being evaluated in a global, multicenter pivotal study in r/r PTCL. At the data cut-off date of February 16, 2023, Golidocitinib has demonstrated strong and durable anti-tumor activity, with an ORR of 44.3%. Over 50% of the patients with tumor remission achieved complete response. The longest duration of response (DoR) exceeded 16 months. Golidocitinib was granted Fast Track Designation for the treatment of r/r PTCL by US FDA in February 2022.