On March 25, 2021 Genetron Holdings Limited ("Genetron Health" or the "Company", NASDAQ:GTH), a leading precision oncology platform company in China that specializes in offering molecular profiling tests, early cancer screening products and companion diagnostics development, reported unaudited preliminary financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Genetron Health Technologies, MAR 25, 2021, View Source [SID1234577169]).

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2020 Financial Highlights

Recorded total revenue of RMB133.9 million (US$20.5 million) for the fourth quarter of 2020 and RMB424.5 million (US$65.1 million) for the full year 2020, representing 30.1% and 31.3% increases over the same period of 2019, respectively.
HCCscreenTM, our most advanced liquid-biopsy early screening product for hepatocellular carcinoma, is currently commercialized as LDT in China. LDT revenue derived from HCCscreenTM sales, as well as IVD revenue largely driven by the sales of S5 instrument and 8-gene Lung Cancer Assay (Tissue), grew significantly in 2020.
Gross margin improved to 62.8% for the fourth quarter 2020 and 61.3% for the full year 2020, compared to 44.5% and 44.8% in the same period of 2019, respectively.
Operating loss narrowed to RMB268.4 million (US$41.1 million) for 2020, from RMB306.9 million in 2019.
Non-IFRS loss(1) improved to RMB215.7 million (US$33.1 million) in 2020, compared to RMB280.2 million in 2019.
2020 Business and Recent Highlights

Successfully raised US$256 million gross proceeds from IPO on Nasdaq.
Early detection – HCCscreenTM:
Genetron Health announced new data on 1,615 patients from its HCCscreenTM prospective cohort study (the "HIT" study). The assay demonstrated 88% sensitivity and 93% specificity, compared to 71% and 95%, respectively, for ultrasound plus AFP combined. HCCscreenTM also achieved 40.9% PPV and 99.3% NPV (detailed press release here).
Exclusive strategic partnership with Chia Tai Tianqing Pharmaceutical Group, a subsidiary of Sino Biopharmaceutical Limited (HKEX: 1177), targeting the hospital market in China.
Selected by the National Cancer Center in China and the Wuxi municipal government for a public health initiative, composing of 150,000 tests over three years.
Received Breakthrough Device Designation by the U.S. FDA.
Joined national R&D project led by the Ministry of Science and Technology in China on lung and digestive cancer early screening.
Obtained NMPA approval on 8-gene Lung Cancer Assay (Tissue), which together with Genetron S5, form a highly efficient in-hospital NGS solution with a two-day turnaround time.
Entered into an exclusive global licensing agreement with ImmuQuad Biotechnologies to develop and commercialize minimal residual disease (MRD) assays in hematologic cancer.
Dr. Yun-fu Hu, formerly deputy director of the U.S. FDA’s Center for Devices and Radiological Health (CDRH) division, joined Genetron Health as Chief Medical Officer. Dr. Hu is tasked to lead the Company’s product development, IVD registration, regulatory affairs, and biopharma business.
Note:
(1) Non-IFRS loss for the period is defined as loss for the period excluding share-based compensation expenses, fair value change and other loss of financial instruments with preferred rights.

"In 2020, despite the challenges caused by the global pandemic, we completed a successful IPO and made significant commercial and clinical progress across all of our business lines. We delivered robust revenue growth with 31.3% year-over-year increase, and we are particularly pleased with the commercial uptakes of HCCscreenTM and our IVD products. Compared to a year ago, our gross margin expanded to 61.3% from 44.8%, and we also markedly improved our SG&A operational efficiencies," remarked Mr. Sizhen Wang, co-founder and CEO of Genetron Health. "We announced new HCCscreenTM data from our prospective cohort study, which showed overall better sensitivity data, and comparable specificity data versus the standard-of-care. We are encouraged by the further validation of this leading liquid-biopsy early detection assay, and will move forward to initiate an NMPA registrational study in the second quarter of this year."

"In 2021, based on the current environment and providing no further major COVID-19-related disruptions in our key markets, we are forecasting our sales to grow around 45% to 47% to reach RMB615 million to RMB625 million. On the pipeline front, we plan to provide case-control early screening data for colorectal cancer this year. Thanks to our Mutation CapsuleTM early screening technology, we are advancing well on our plans to expand our single-cancer assay to become a multi-cancer product. We also continue to make progress on our MRD projects in liver and colorectal cancers. Overall, Genetron Health is well-positioned to capture market share in the fast-growing precision oncology sector, and we are excited about our growth prospects. More importantly, we remain highly committed to developing innovative products that would benefit cancer patients and save more lives," concluded Mr. Wang.

Fourth Quarter 2020 Unaudited Preliminary Financial Results

Total revenue for the fourth quarter 2020 increased by 30.1% to RMB133.9 million (US$20.5 million) from RMB102.9 million in the same period of 2019.

Diagnosis and monitoring revenue increased by 44.0% to RMB123.5 million (US$18.9 million) in the fourth quarter 2020 from RMB85.8 million in the same period of 2019. The increase was driven by the growth in the revenues generated from both the provision of LDT services, particularly in early screening, and the sale of IVD products.

Revenue generated from the provision of LDT services increased by 48.5% to RMB96.9 million (US$14.9 million) during the fourth quarter 2020 from RMB65.3 million in the same period of 2019. In the fourth quarter, sales of LDT services included sales of our early screening test, HCCscreenTM, which contributed to growing portion of total LDT revenue. LDT diagnostic tests sold in the fourth quarter 2020 totaled approximately 5,340 units, representing a decrease of 16% compared to the number of LDT diagnostic tests sold in the same period of 2019, primarily due to the resurgence of COVID-19 in our key sales territories in the fourth quarter. However, the average selling price increased compared to the same period in 2019, attributable to a shift to higher value products such as Onco PanScan, and better pricing management.
Revenue generated from sale of IVD products increased by 29.5% to RMB26.5 million (US$4.1 million) in the fourth quarter 2020 from RMB20.5 million in the fourth quarter 2019. The increase was mainly driven by the increase in the number of assays and sequencing platforms sold in the fourth quarter 2020.

On March 25, 2021 Pfizer Inc. (NYSE:PFE) reported the peer-reviewed publication of real-world evidence (RWE) demonstrating that first-line therapy with IBRANCE (palbociclib) in combination with letrozole was associated with improved real-world progression-free survival (rwPFS) and overall survival (OS) in women with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (mBC) compared with letrozole alone (Press release, Pfizer, MAR 25, 2021, View Source;Metastatic-Breast-Cancer [SID1234577168]). These findings represent the first comprehensive comparative effectiveness analysis of survival outcomes for a CDK 4/6 inhibitor in routine clinical practice and were published online in Breast Cancer Research.

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At a median follow-up of approximately two years and after balancing for baseline demographic and clinical characteristics, median rwPFS was 20.0 months with IBRANCE plus letrozole versus 11.9 months with letrozole alone (HR 0.58: 95% CI, 0.49 to 0.69; p<0.0001) in this observational, retrospective real-world analysis. Median OS was not reached among patients in the IBRANCE group and was 43.1 months among patients in the letrozole group (HR 0.66: 95% CI, 0.53 to 0.82; P=0.0002). These findings represent a 42% reduction in the risk of progression and a 34% reduction in the risk of death.

"Real-world evidence is woven into the fabric of how we innovate and advance care for patients with breast cancer, supporting our randomized clinical trials," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "With more than six years of patient experience, a positive benefit-risk profile, strong clinical data and robust real-world data, the totality of evidence solidifies the role of IBRANCE plus endocrine therapy as a treatment for patients with HR+, HER2- metastatic breast cancer."

The analysis also showed the two-year OS rate was 78.3% in the IBRANCE group and 68.0% with letrozole. The rwPFS and OS benefits were generally consistent across all subgroups, including younger patients (18-50 years of age) and site or extent of metastases.

"Real-world evidence is increasingly used to complement traditional randomized clinical trial data to better understand a therapy’s effectiveness in routine clinical practice and inform treatment decisions," said Angela DeMichele, M.D., lead researcher and Professor in Breast Cancer Excellence in the Perelman School of Medicine at the University of Pennsylvania. "The findings from this landmark real-world study align with the positive impact that I have seen in my own patients treated with IBRANCE combination therapy."

The data for this retrospective observational analysis was collected from the Flatiron Health de-identified longitudinal database, which includes patient records from Flatiron’s network of more than 280 community cancer clinics and partnerships with major academic cancer centers across the U.S. This real-world cohort includes more than 1,400 women with HR+, HER2- mBC with any extent of visceral disease. Safety data were not collected as part of this analysis.

The data from this real-world analysis is consistent with available data from the Phase 3 PALOMA-2 trial, which studied IBRANCE plus letrozole versus placebo plus letrozole as initial endocrine-based therapy in post-menopausal women with estrogen-receptor positive (ER+), HER2- mBC. However, this observational analysis differs from the randomized clinical trial in several ways. The studies have different endpoints and there are inherent limitations in real-world observational studies, including lack of randomization, lack of uniform timing or type of clinical assessments and challenges with missing data. OS data is being collected in the PALOMA-2 randomized clinical trial but is not yet mature.

About the IBRANCE Real-World Evidence Program

Since the initial approval by the U.S. Food and Drug Administration more than six years ago, IBRANCE has been prescribed to more than 380,000 patients across more than 100 countries. With this breadth of real-world experience, Pfizer is working to build the most extensive body of RWE for a CDK 4/6 inhibitor. This RWE program is generating data from multiple studies involving more than 4,000 patients around the world and continues to expand. These studies – IRIS, POLARIS, MARIA, and MADELINE – include diverse patient populations treated in everyday clinical practice and are collecting data related to clinical outcomes, translational data and quality of life endpoints, which complement the data generated from the PALOMA randomized clinical trials. Pfizer will continue to share new data from these studies with the scientific community as results becomes available.

About IBRANCE (palbociclib) 125 mg tablets and capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.2,3 In the U.S., IBRANCE is indicated for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.

On March 25, 2021 OncoSec Medical Incorporated (NASDAQ:ONCS) (the "Company" or "OncoSec"), a biotechnology company focused on cytokine-based intratumoral cancer immunotherapies, reported it will sponsor a key opinion leader (KOL) webinar to be held by LifeSci Advisors discussing the anti-PD-1 checkpoint refractory metastatic melanoma landscape and the impact of the results from ILLUMINATE-301 on Wednesday, March 31, 2021 at 12:00 p.m. ET (Press release, OncoSec Medical, MAR 25, 2021, View Source [SID1234577167]).

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The webinar features presentations by KOLs Gregory Daniels, M.D., Ph.D., UC San Diego Health, Paolo Ascierto, M.D., National Tumor Institute Fondazione G. Pascale, John M. Kirkwood, M.D., University of Pittsburgh, and Matteo Carlino, M.D., Westmead and Blacktown Hospitals.

A Fireside Chat moderated by Neil Canavan, author of "The Cure Within," will follow the formal presentations and the KOLs will be available to answer questions afterward.

To register for the event, please click here.

The KOLs will discuss the anti-PD-1 checkpoint refractory metastatic melanoma landscape and commercial outlook:

Gregory Daniels, M.D., Ph.D., UC San Diego Health, will lead the discussion on tumor-infiltrating lymphocytes (TILs). Dr. Daniels, a board-certified oncologist, coordinates care for patients with melanoma, skin cancers and head and neck cancers. Dr. Daniels treats certain skin cancers with highly effective immunotherapy approaches. He is part of the Precision Immunotherapy Clinic, which offers the most promising investigational immunotherapies for many types of cancer. As a professor in the Department of Medicine, Dr. Daniels is involved in training medical students, residents and fellows at UC San Diego School of Medicine. Active in research, much of his work has focused on understanding the link between autoimmunity and tumor immunity in developing more effective and less toxic immune-stimulatory approaches for patients with melanoma. Dr. Daniels completed his fellowship and residency at Mayo Clinic in Rochester, Minn. and earned his medical degree from University of Southern California Keck School of Medicine.

Paolo Ascierto, M.D., National Tumor Institute Fondazione G. Pascale, will co-lead the discussion on intratumoral (IT) toll-like receptor (TLR) 9. Dr. Ascierto is the Director of the Dept. of Melanoma, Cancer Immunotherapy and Development Therapeutics at the National Tumor Institute IRCCS Fondazione G. Pascale in Naples, Italy. He previously served as a postdoctoral fellow and then as vice-director of the Department of Clinical Immunology. His research interest has focused on diagnosis and treatment of melanoma, including assessment of new molecular markers for tumor progression, targeted therapies, immunotherapy and vaccination treatments. He has served as principal investigator in numerous clinical trials and has published numerous peer-reviewed articles on these topics. He earned his M.D. and received board-certification in oncology from the University of Naples.

John M. Kirkwood, M.D., University of Pittsburgh, will co-lead the discussion on intratumoral (IT) toll-like receptor (TLR) 9. Dr. Kirkwood, M.D. is board-certified in internal medicine and medical oncology and is Professor of Medicine at the University of Pittsburgh. He received his medical degree from Yale University School of Medicine, where he was also an intern and resident in internal medicine. His subspecialty is in medical oncology and he completed his fellowship in this field at the Dana Farber Cancer Institute and Harvard Medical School. Dr. Kirkwood’s early research in tumor immunology was done at Memorial Sloan Kettering and his postdoctoral fellowship work in tumor immunology at Harvard University. He is a member of the New York Academy of Sciences, the American Society for Clinical Oncology, the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the American Medical Association, the Eastern Cooperative Oncology Group, the National Cancer Foundation, the International Society for Interferon and Cytokine Research, the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), the Society for Melanoma Research, the Clinical Immunology Society and the Society of Natural Immunity.

Matteo Carlino, M.D., Westmead and Blacktown Hospitals, will lead the discussion on IT DNA plasmid-based Interleukin-12 (IL-12). Dr. Carlino is a Medical Oncologist at Westmead and Blacktown Hospitals, where he leads melanoma clinical trials program, a Clinical associate professor at The University of Sydney and a Faculty Member at MIA. He undertook a Ph.D. examining predictors of response and mechanisms of resistance to BRAF and MEK inhibitor treated melanoma. Dr. Carlino continues to be involved in the translational research program based at MIA and the Westmead Institute for Cancer Research. He is an investigator on multiple Phase I, II and III clinical trials in melanoma targeted and immunotherapy.

On March 25, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that initial patient enrollment in the second dose cohort in the Phase 1 portion of the Actimab-A venetoclax Phase 1/2 combination trial in fit and unfit patients with relapsed or refractory Acute Myeloid Leukemia (r/r AML) has been completed (Press release, Actinium Pharmaceuticals, MAR 25, 2021, View Source [SID1234577166]). The Phase 1 portion of the trial is a 3 + 3 dose escalation study to determine the maximum tolerable dose of Actimab-A that is to be studied in the Phase 2 portion of the study. Based on the progress of enrollment, Actinium expects to complete the Phase 1 portion and present further proof-of-concept data in the second half of 2021.

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First-in-human data from the first dose cohort of 0.5 μCi/kg of Actimab-A and Venetoclax were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2020. Patients enrolled in the first dose cohort had a median of 2 prior therapies (range 2-3) and a median bone marrow blast percentage of 30% (range 20 – >60). All 3 patients had poor risk disease with adverse cytogenetics, and each patient had an additional high-risk marker (FLT3-ITD+, antecedent JAK2+ myelofibrosis, or TP53 mutation). One patient who had multiple genetic mutations including IDH2, RUNX1, TP53 and others, achieved a complete remission with incomplete blood count recovery (CRi) after the first cycle of Actimab-A and venetoclax. Next generation sequencing at the end of the first cycle showed that the patient was negative for the known IDH2 and RUNX1 mutations. In addition, another patient achieved a partial response after one cycle of Actimab-A and venetoclax. There were no Actimab-A related dose limiting toxicities or nonhematologic Grade 3 or greater related AEs reported in the first cohort.

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "We are encouraged by the strong progress we are making in this novel combination trial and excited to be studying Actimab-A with venetoclax. Venetoclax has emerged as a standard of care and backbone therapy for patients with AML who are both fit and unfit, however, patients with relapsed or refractory disease have poor outcomes and therefore need better treatment options. Based on the synergistic mechanism of action and preliminary clinical evidence from the first cohort, we are optimistic that Actimab-A in combination with venetoclax can improve outcomes for patients with relapsed or refractory disease using the unique targeted radiation mechanism of Actimab-A. We look forward to presenting data from this cohort of patients as well additional clinical data from the Phase 1 portion of the trial and working to advance this novel combination in the clinic."

In a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting Mcl-1, a protein shown to mediate resistance to venetoclax. Further, the induction of direct AML cell death via double-stranded DNA breaks via the radioisotope Actinium-225 in Actimab-A provides a second mechanism for enhancing synergistic potency with venetoclax. Venetoclax is a B-Cell Lymphoma 2 (Bcl-2) inhibitor that is jointly developed and marketed by AbbVie and Genentech and is approved for patients with AML, Chronic Lymphocytic Leukemia (CLL), and Small Lymphocytic Leukemia (SLL). Despite its approval in AML, venetoclax has produced low response rates of 19% as a single agent in R/R AML.1 A Phase 2 trial studying Actimab-A as a single agent produced a 69% overall response rate in older unfit patients with newly diagnosed AML.

Sandesh Seth, Actinium’s Chairman and CEO, added, "This trial is an exciting evolution of our Actimab-A program and application of the isotope Actinium-225. Actinium-225 is a potent medical isotope that can kill a cancer cell with a single alpha particle hit, emits four alpha particles in its decay and can cause double strand DNA breaks for which cancer cells have no known repair or resistance mechanism. Its energy is also emitted over a very short path length equal to a few cells in diameter enabling precise cell killing while sparing normal cells to limit systemic toxicities. With clinical experience in nearly 150 patients, robust IP and a clinically validated supply chain, we are leaders in the rapidly growing field of targeted alpha radiotherapy and specifically Actinium-225. Through continued clinical progress and innovation driven by our R&D efforts, we are committed to advancing our leadership position in the field of Actinium-225 based therapies and applying them with the goal of improving patient outcomes."

1 Aldoss et al. Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia. Haematologica2018.1888094.

About Actinium’s CD33 Program

Actinium’s CD33 program is evaluating the clinical utility of Actimab-A, an ARC comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as patients with multiple myeloma. The CD33 development program is driven by data from over one hundred treated patients, including a Phase 1/2 trial where Actimab-A produced a remission rate as high as 69% as a single agent. This clinical data is shaping a two-pronged approach for the CD33 program, where at low doses the Company is exploring its use for therapeutic purposes in combination with other modalities and at high doses for use for targeted conditioning prior to bone marrow transplant. Actinium currently has multiple clinical trials ongoing including the Phase 1 Actimab-A CLAG-M and Phase 1/2 Actimab-A venetoclax combination trials and is exploring additional CD33 ARC combinations with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.

On March 25, 2021 Kadmon Holdings, Inc. (NASDAQ:KDMN) reported it will present a trial-in-progress poster on KD033-101, the Company’s ongoing dose-escalation, dose-expansion trial of KD033 in patients with metastatic and locally advanced solid tumors, at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place virtually April 10 – 15, 2021 (Press release, Kadmon, MAR 25, 2021, View Source [SID1234577165]).

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KD033 is currently being evaluated in an ongoing Phase 1 study in patients with metastatic or locally advanced solid tumors. Initial safety data from the trial are anticipated in Q2 2021. Additional clinical data from the trial are anticipated in Q4 2021.

Details of the AACR (Free AACR Whitepaper) trial-in-progress poster are outlined below:

KD033-101 Poster Presentation

Title: A Phase 1 Multiple Ascending Dose Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally Advanced Solid Tumors

Category: Session PO.CT08.01 – Phase I Clinical Trials in Progress

Date/Time: April 10, 2021, 8:30 AM – 11:59 p.m. ET

Abstract ID: CT227

About the KD033-101 Clinical Trial

KD033-101 is a Phase 1, open-label, dose-escalation and dose-expansion study investigating the safety and efficacy of KD033 in patients with metastatic or locally advanced solid tumors. The dose-escalation phase of the study will evaluate the pharmacokinetics and pharmacodynamics and identify the maximum tolerated dose (MTD) of KD033. The dose-expansion phase of the study will enroll patients who have progressed or are refractory to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy to assess safety, efficacy and determine the recommended Phase 2 dose (RP2D) of KD033.

About KD033

KD033 is a novel immunotherapy developed in-house and is fully owned by Kadmon. KD033 combines an anti-PD-L1 antibody with IL-15, a cytokine that expands key tumor-fighting cell types, including natural killer (NK), natural killer T (NKT) and memory T cells, to potentially induce durable responses and inhibit tumor growth. The anti-PD-L1 antibody directs IL-15 activity to the tumor microenvironment, limiting systemic exposure of IL-15 to potentially increase safety and tolerability. KD033 was well tolerated in GLP toxicology studies at clinically relevant doses. KD033 process development and manufacturing was completed through a successful collaboration with Wuxi Biologics and exhibited desired manufacturability and stability criteria.

KD033 is the most advanced candidate from Kadmon’s IL-15 fusion protein platform. The Company is developing a portfolio of therapies combining IL-15 with select antibodies for the treatment of cancer.