On June 2, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for olverembatinib for the treatment of patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) who had received first-line treatment (Press release, Innovent Biologics, JUN 2, 2023, View Source [SID1234632403]).

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Results from an ongoing Phase 1b/2 study of olverembatinib in China showed an impressive clinical benefit rate (CBR) of 93.8% in patients with this subtype of GIST. Based on these promising results, the study was selected for presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting for two consecutive years[1].

Olverembatinib is the first and only third-generation BCR-ABL inhibitor approved in China for the treatment of adult patients with tyrosine kinase inhibitors (TKI)-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation as confirmed by a validated diagnostic test. Olverembatinib is jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

This marks the second BTD granted to olverembatinib by the CDE, with the first one granted in March 2021 for the treatment of patients with CML-CP resistant and/or intolerant to first- and second-generation TKIs. A New Drug Application (NDA) for the first BTD indication was accepted by the NMPA in July 2022 and subsequently granted Priority Review designation that will support a full approval of olverembatinib.

Dr. Hui Zhou, Senior Vice President of Innovent stated:" We are glad to see the NMPA grants another BTD for olverembatinib, marking a major milestone in its clinical development and demonstrating its therapeutic potentials beyond hematologic malignancies. We look forward to more good news of olverembatinib that allow more patients to benefit from this novel drug as soon as possible."

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify a drug candidate to receive status for rapid review by the CDE, but it will also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace. Click here for the published list of drugs which have been granted BTD by NMPA.

About Gastrointestinal Stromal Tumor (GIST)

GIST is a type of malignancy that arises in mesenchymal tissues of the gastrointestinal tract, and most patients with GIST harbor KIT or PDGFRA mutations. The introduction of TKIs has significantly improved the prognosis of these patients. However, patients with SHD-deficient GIST, a rare subtype of GIST, still have considerable unmet medical needs. It is known to the research community that patients with SDH-deficient GIST are commonly insensitive to existing TKIs. Although patients with early-stage localized disease can benefit from surgical treatment, most of them eventually experience relapse[2]-[6]. At present, there is no standard of care for patients with relapsed or advanced SDH-deficient GIST, whose 5-year event-free survival (EFS) is only 24%[2]-[6].

About Olverembatinib

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing Program in China, the orally active, third-generation BCR-ABL inhibitor olverembatinib is the first China-approved third-generation BCR-ABL inhibitor targeting drug-resistant chronic myeloid leukemia (CML). Olverembatinib can effectively target a spectrum of BCR-ABL mutants, including the T315I mutation.

In November 2021, olverembatinib was granted a conditional approval through the Priority Review process by the China National Medical Products Administration (NMPA) for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation as confirmed by a validated diagnostic test. Subsequently, Olverembatinib was included into the China 2022 National Reimbursement Drug List (NRDL) for the approved indication. In March 2021, olverembatinib was granted a Breakthrough Therapy Designation (BTD) by the CDE for the treatment of patients with CML-CP who are resistant and/or intolerant of first- and second-generation TKIs.

In overseas, olverembatinib was cleared by the US FDA in July 2019 to directly enter a Phase Ib study. Since 2018, the clinical results of olverembatinib have been selected for oral presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meetings for five consecutive years, and was nominated for "Best of ASH (Free ASH Whitepaper)" in 2019. To date, olverembatinib has been granted one Fast Track Designation (FTD) and four Orphan Drug Designations (ODDs) from the US Food and Drug Administration (FDA) for the treatment of CML, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and gastrointestinal stromal tumour (GIST); and one Orphan Designation from the European Medicines Agency (EMA) of the European Union for the treatment of CML.

In July 2021, Ascentage Pharma (6855.HK) and Innovent Biologics (1801.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in China.

*Olverembatinib has not been approved for any indication in the U.S.

On June 2, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the presentation of top-line data from the Pivotal Phase 2 FELIX study of obe-cel in adult r/r B-cell Acute Lymphoblastic Leukemia (B-ALL) at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Autolus, JUN 2, 2023, View Source [SID1234632402]).

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In the pivotal morphological cohort of the FELIX trial, 112 patients with r/r adult ALL were enrolled and 94 (84%) patients were dosed with obe-cel. Of the dosed patients, 76% patients achieved a complete response (CR) or CR with incomplete haematological recovery (CRi), and 97% of the responders with evaluable samples were in deep remission with no detectable minimal residual disease (MRD). Furthermore, at a 9.5-month median follow up, 61% of responders remained in ongoing remission without new anti-cancer therapies. CAR T cellular kinetics demonstrate excellent CAR T engraftment and persistence and are consistent with the prior ALLCAR19 study.

Safety analysis demonstrated a potentially best-in-class tolerability profile with Grade ≥3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 3% (3/94) and 7% (7/94) of patients, respectively. Most of the toxicity was seen in patients with high disease burden. Notably, 6 of 7 Grade ≥3 ICANS were observed among patients with very high tumor burden of more than 75% bone marrow blasts at lymphodepletion. Overall, Grade ≥3 adverse events occurred in 79% of patients, with neutropenia (36.2%), and thrombocytopenia (25.5%) most commonly reported.

Manufacturing was reliable and consistent, with product released for 94% of leukapheresed patients and median turnaround times of 21 days from vein to release.

"We are very encouraged by the outcome of the FELIX study. Obe-cel shows low immunotoxicity, high complete remission rates and excellent CAR T expansion and persistence in adult B-ALL. These data are consistent with the prior ALLCAR19 study and suggest that obe-cel has the potential for long-term clinical benefit in adult B-ALL patients without additional therapies," said Dr. Claire Roddie, Associate Professor at UCL, Honorary Consultant Haematologist at UCLH.

"We are pleased that our pivotal FELIX study confirms the attractive product profile for obe-cel, combining a high level of clinical activity with an excellent safety profile which we know is critical for this highly pre-treated and frail patient population. Conducting this study through the pandemic was a pressure test for obe-cel’s product profile and our ability to deliver obe-cel reliably under difficult circumstances. We would like to thank patients, their care givers, nurses and treating physicians for their participation in the FELIX study," said Dr. Christian Itin, Chief Executive Officer of Autolus.

"With the Nucleus, our commercial manufacturing facility, well advanced in validation we look forward to submitting a BLA towards the end of this year and working with the FDA to get obe-cel to patients as soon as possible."

ASCO Oral Presentation, abstract #7000:

Title: Safety and efficacy of Obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR in relapsed/refractory adult B-Cell acute lymphoblastic leukemia (r/r B-ALL): Topline results of the pivotal FELIX study

Session Title: Hematologic Malignancies — Leukemia, Myelodysplastic Syndromes, and Allotransplant
Session date and time: Friday, June 2, 2023, 2.00 pm –2.12 pm ET, 7.00 pm – 7.12 pm BST
Presenting Author: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Additional data from the FELIX study will be presented as an Oral Presentation at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) meeting:

Title: Safety and efficacy of Obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR in relapsed/refractory adult B-Cell acute lymphoblastic leukemia (r/r B-ALL): Topline results of the pivotal FELIX study

Presentation ID: S262
Session date and time:
Saturday, June 10, 2023, 11.00 am – 11.15 am ET, 4.00 pm – 4.15 pm BST
Presenting Author: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Conference Call

Autolus will host a conference call and webcast today for analysts at 4.00 pm ET/9.00 pm BST to summarize the ASCO (Free ASCO Whitepaper) data. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call.

A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.

On June 2, 2023 Novartis reported positive primary endpoint data from the pivotal Phase III NATALEE trial at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Novartis, JUN 2, 2023, View Source [SID1234632401]). Data showed that Kisqali (ribociclib) plus endocrine therapy (ET), compared to ET alone, lowered the risk of cancer recurrence by 25.2% in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (HR=0.748; 95% CI: 0.618, 0.906; p=0.0014) along with a consistent, clinically meaningful invasive disease-free survival (iDFS) benefit across key pre-specified subgroups (see table below)1.

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Kisqali iDFS benefit across key pre-specified subgroups1:

Hazard Ratio 95% CI
Intention-To-Treat Population 0.748 0.618, 0.906 (p=0.0014)
AJCC Tumor Stage II 0.761 0.525, 1.103
AJCC Tumor Stage III 0.740 0.592, 0.925
Node-positive disease 0.771 0.630, 0.944
Node-negative disease 0.630 0.341, 1.165
Pre-menopausal women and men 0.722 0.530, 0.983
Post-menopausal women 0.781 0.613, 0.997
Kisqali data across all secondary efficacy endpoints was also consistent, including distant disease-free survival (DDFS) (26% risk reduction) and recurrence-free survival (RFS) (28% risk reduction), with a trend for improvement in overall survival (OS) (HR=0.759; 95% CI: 0.539, 1.068)*1.

The safety profile of Kisqali at 400 mg was favorable with low rates of symptomatic adverse events (AEs) and limited need for dose modifications when administered up to three years1. The most frequently reported AEs of special interest (grade 3 or higher) were neutropenia (43.8%) and liver-related AEs (e.g. elevated transaminases) (8.3%)1. Grade 3 or higher QT interval prolongation and diarrhea were low for Kisqali at 1.0% and 0.6%, respectively1.

"These landmark results will fundamentally change how we treat patients with stage II and III HR+/HER2- early breast cancer who are in need of new, well-tolerated options that prevent their cancer from coming back," said Dennis J. Slamon, M.D., Director of Clinical/Translational Research, UCLA Jonsson Comprehensive Cancer Center and Chairman and Executive Director of Translational Research In Oncology (TRIO) and NATALEE trial lead investigator. "Addressing this unmet need across such a broad patient population could help streamline treatment decisions for healthcare providers and keep many more at-risk patients cancer-free without disrupting their daily lives."

"Patients diagnosed with HR+/HER2- early breast cancer remain at risk of cancer recurrence, given that one-third of patients diagnosed with stage II and more than half of those diagnosed with stage III will unfortunately experience a return of their cancer," said Shreeram Aradhye, M.D., President, Global Drug Development and Chief Medical Officer, Novartis. "The compelling data from NATALEE highlight the potential of Kisqali to reduce the risk of cancer recurrence in this at-risk population, including node-negative patients, while maintaining a favorable safety profile. These potentially practice-changing results reinforce the unique and well-established profile of Kisqali as a proven treatment in HR+/HER2- metastatic breast cancer."

"After an early breast cancer diagnosis, patients live with a persistent and lifelong worry that their cancer will return," said Fran Visco, President, National Breast Cancer Coalition, and member of the NATALEE Steering Committee. "The National Breast Cancer Coalition partners with industry and scientists to help find treatments that will make certain that does not happen. Educated patient advocate participation in all phases of research, especially in designing and implementing clinical trials, is critical to making certain patients have meaningful options, and we are grateful that Novartis welcomed our collaboration and participation in all aspects of the NATALEE trial."

Novartis plans to submit these Phase III data to regulatory authorities in the US and Europe before end of year.

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali with ET as adjuvant treatment versus ET alone in patients with HR+/HER2- EBC, being conducted in collaboration with TRIO1. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable1. The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria1. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial1.

Results showed Kisqali plus ET, compared to ET alone, lowered the risk of cancer recurrence by 25.2% (HR=0.748; 95% CI: 0.618, 0.906; p=0.0014), along with consistent clinically meaningful iDFS benefit across key pre-specified subgroups: AJCC Tumor Stage II (HR=0.761; 95% CI: 0.525, 1.103), AJCC Tumor Stage III (HR=0.740; 95% CI: 0.592, 0.925), node-negative disease (HR=0.630; 95% CI: 0.341, 1.165), node-positive disease (HR=0.771; 95% CI: 0.630, 0.944), pre-menopausal women and men (HR=0.722; 95% CI: 0.530, 0.983), post-menopausal women (HR=0.781; 95% CI: 0.613, 0.997)1. Kisqali data across all secondary efficacy endpoints was also consistent, including DDFS (26% risk reduction) and RFS (28% risk reduction), with a trend for improvement in OS (HR=0.759; 95% CI: 0.539, 1.068)*1.

Median study duration of follow up was 34 months (range 21-48 months) with clinical benefits observed after approximately two years1. NATALEE explored a lower starting dose (400 mg) of Kisqali than the dose approved for treatment in metastatic breast cancer (MBC) (600 mg) with the goal to minimize disruptions to patient quality of life without compromising efficacy. The safety profile of Kisqali at 400 mg was favorable with low rates of symptomatic AEs and limited need for dose modifications when administered up to three years1. The most frequently reported AEs of special interest (grade 3 or higher) were neutropenia (43.8%) and liver-related AEs (e.g. elevated transaminases) (8.3%)1. Grade 3 or higher QT interval prolongation and diarrhea were low for Kisqali at 1.0% and 0.6%, respectively1.

*Results based on pre-specified interim analysis for OS at time of primary iDFS analysis; additional follow up is planned to obtain more mature OS data1.

About Early Breast Cancer
More than 90% of patients diagnosed with breast cancer have EBC3. Despite standard-of-care adjuvant therapy, approximately one-third of those diagnosed with stage II and more than half of those diagnosed with stage III HR+/HER2- EBC experience cancer recurrence4,5. The risk of recurrence continues over decades with more than half of breast cancer recurrences occurring five or more years after diagnosis4,6. For many of these patients, there are currently no targeted therapeutic options outside of the standard chemotherapy and ET7.

About Kisqali (ribociclib)
Kisqali has consistently demonstrated OS benefit while preserving or improving quality of life across three Phase III trials in MBC8-19. Updates to the NCCN Guidelines for breast cancer, released in January 2023, recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when combined with an aromatase inhibitor (AI)20. Additionally, Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO (Free ESMO Whitepaper) Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line pre-menopausal patients with HR+/HER2- advanced breast cancer21. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for post-menopausal patients with HR+/HER2- advanced breast cancer treated in the first line22.

Kisqali has been approved in 99 countries worldwide, including by the United States Food and Drug Administration (FDA) and the European Commission. In the U.S., Kisqali is approved for the treatment of adult patients with HR+/HER2- advanced or MBC in combination with an AI as initial ET or fulvestrant as initial ET or following disease progression on ET in post-menopausal women or in men. In the EU, Kisqali is approved for the treatment of women with HR+/HER2- advanced or MBC in combination with either an AI or fulvestrant as initial ET or following disease progression. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist19.

Novartis is committed to continuing to study Kisqali in breast cancer. Novartis is collaborating with SOLTI, which is leading the HARMONIA study to test whether Kisqali changes tumor biology to enable a better response to ET compared to Ibrance** (palbociclib) for patients with HR+/HER2-, HER2-enriched subtype23 MBC, and with the Akershus University Hospital in Norway on the NEOLETRIB trial, a neoadjuvant Phase II trial studying the effects of Kisqali in HR+/HER2- EBC to discover the potentially unique underlying mechanism of action24.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

Please see full Prescribing Information for Kisqali, available at www.Kisqali.com

On June 2, 2023 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that it will present at the following investor conferences in June (Press release, UroGen Pharma, JUN 2, 2023, View Source [SID1234632399]):

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Jefferies 2023 Healthcare Conference — June 7-9, 2023

Fireside Chat Date: Friday, June 9th from 12:45-1:10pm ET
Webcast Link: View Source

Goldman Sachs 44th Annual Global Healthcare Conference — June 12-15, 2023

Fireside Chat: Wednesday, June 14th from 4:00-4:35pm ET
Webcast Link: View Source
Webcasts for both the Jefferies and Goldman Sachs fireside chats will be available via the Investors section of UroGen’s website, www.urogen.com. A replay of each webcast will be available on the Company’s website for approximately 90 days.

On June 2, 2023 TRACON Pharmaceuticals, Inc. (Nasdaq: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with other life science companies to develop and commercialize innovative products in the United States, reported that Charles Theuer, M.D., Ph.D., President and Chief Executive Officer, will present a corporate overview at the Jefferies Healthcare Conference on Friday, June 9, 2023 at 8:30 am Eastern Time (Press release, Tracon Pharmaceuticals, JUN 2, 2023, View Source [SID1234632398]).

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To access a live webcast or replay of the presentation, please visit the "Events and Presentations" page within the "Investors" section of the TRACON Pharmaceuticals website at www.traconpharma.com.