Scholar Rock Presents Preclinical Data for SRK-181 at the TGFβ for Immuno-Oncology Drug Development Summit

On January 27, 2021 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported a presentation at the 2021 TGFβ for Immuno-Oncology Drug Development Summit (Press release, Scholar Rock, JAN 27, 2021, View Source [SID1234574348]).

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"Inhibition of TGFβ1 Activation with SRK-181 Overcomes Primary Resistance to Checkpoint Inhibition Therapy" will be presented on January 28th, 2021 at 12:30 PM EST. The presentation will provide an overview of the preclinical data demonstrating selective inhibition of TGFβ1 activation with SRK-181-mIgG1 (murine version of SRK-181) induces combination treatment effects with anti-PD-1 on tumor growth in checkpoint inhibition therapy-resistant tumors as well as an improved preclinical toxicity profile compared to less selective TGFβ inhibition.

Scholar Rock will also be participating in a panel discussion titled "Debating the Best Approach to Target TGF-β" on January 27th, 2021 at 10:45 am EST.

About SRK-181

SRK-181 is a potent and highly selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to anti-PD-(L)1 therapy, data suggests TGFβ1 is a key contributor to excluding immune cell entry into the tumor microenvironment, thereby preventing normal immune function. Scholar Rock believes SRK-181 has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy. By specifically targeting the latent TGFβ1 isoform, Scholar Rock hypothesizes that SRK-181 can increase the therapeutic window by potentially avoiding toxicities associated with non-selective TGFβ inhibition. A Phase 1 proof-of-concept clinical trial in patients with locally advanced or metastatic solid tumors is ongoing. The effectiveness and safety of SRK-181 have not been established and SRK-181 has not been approved for any use by the FDA or any other regulatory agency.

Genetron Health to Release Thirteen Research Findings at 21st World Conference on Lung Cancer

On January 27, 2021 Genetron Holdings Limited ("Genetron Health" or the "Company") (Nasdaq: GTH), a leading precision oncology company in China that specializes in offering molecular profiling tests, early cancer screening products and companion diagnostics development, reported that it will release thirteen new research findings at the 21st World Conference on Lung Cancer (WCLC), which will be held virtually from January 28 to 31 (Press release, Genetron Health Technologies, JAN 27, 2021, View Source [SID1234574347]). One of the research findings (Study 3713) was selected for a mini oral presentation.

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Genetron Health joined hands with eight top Chinese hospitals to conduct in-depth analysis and research on a large-scale lung cancer cohort, leveraging the Genetron One-Step Seq Method and core products such as Onco PanscanTM. The research has achieved key findings in gene mutation and fusion feature mapping, immunotherapy marker detection, bioinformatics analysis, etc., laying the groundwork for further exploration of lung cancer diagnosis, treatment and the design of treatment solutions.

Exploring the characteristics of gene mutation

Seven studies (#1766, #2150, #2226, #2007, #1780, #1452, #835) on EGFR mutations, JAK family gene mutations, FGFR1-4 mutations, KIT activating mutations, mTOR signaling pathway mutations, and IDH1/2 mutations, respectively, were conducted to explore their mutation patterns and distribution characteristics in Chinese lung cancer patients, and to search for drug-resistant targets and effective solutions.

Exploring the characteristics of gene fusion

Study 3609 involved an in-depth analysis of 10 gene fusion patterns and distributions in the Chinese lung cancer population, as well as their co-occurrences with other driver mutations, in order to construct initial gene fusion mapping. Study 3601 focused on the prevalence and clinical benefit ratio of NTRK1 rare fusion in the Chinese lung cancer population.

Detecting immunotherapy markers

Study 3698 demonstrated the usage of KMT2C/D gene mutations as a positive predictor of the efficacy of non-small cell lung cancer (NSCLC) immunotherapy, indicating that patients with such gene mutations may benefit from immunotherapy. Study 3713 focused on the differences amongst DDR (DNA Damage Response) signaling pathway-related gene mutations in NSCLC and small cell lung cancer (SCLC), supporting the research of immunotherapy in the two patient groups.

Optimizing bioinformatics models

Based on six CpG sites, Study 2231 developed a random forest classification model, a new type of bioinformatics model, to distinguish early lung adenocarcinoma from benign nodules.

Rare case research

Study 3630 used Genetron’s One-Step Seq patented technology (Chinese Invention Patent No. ZL 201710218529.4) in the detection of a very rare patient with dual ROS1 fusion lung adenocarcinoma in a cohort of 180 people, demonstrating an efficacy greater than those of common diagnostic methods. In addition, the study noted the patient’s positive reaction to crizotinib, which indicates a direction for future research on the mechanism of this rare phenomenon.

"The thirteen research findings we are releasing at the WCLC, which focus on the characteristics of the Chinese lung cancer population, have made discoveries in multiple dimensions and demonstrated Genetron Health’s strong capabilities in the fundamental research of lung cancer genomics," said Dr. Hai Yan, Co-founder and Chief Scientific Officer of Genetron Health. "The research findings regarding EGFR, JAK, FGFR and other mutation patterns, and drug resistance studies can enhance the development of more diverse and personalized medication strategies for patients. Gene fusion mapping can guide the design of more advanced and rich diagnostic products. The discovery of KMT2C/D mutations indicates more possibilities for lung cancer patients to benefit from immunotherapy treatments. In addition, the rare cases detected through Genetron Health’s patented research technology will draw more attention to and promote further research on relevant cancer diagnosis and treatment."

ABSTRACT NUMBER

ABSTRACT TITLE

2226

Identification of FGFR Mutations in Chinese Lung Cancer Patients by Next-Generation Sequencing

3609

Exploration of the Gene Fusion Landscape of Lung Cancer in a Chinese Retrospective Analysis

2150

Next generation sequencing reveals the genetic landscape of JAK family in Chinese lung cancer patients

1766

Comprehensive investigation of uncommon EGFR mutations in 14,429 Chinese lung cancer patients

1780

Next-generation sequencing guided the gene mutations associated with mTOR-inhibitors in Chinese lung cancer patients

3601

The prevalence of NTRK1 fusion in a Chinese lung cancer cohort

3630

A recommended one-step targeted sequencing technology for identification of a dual CD74-ROS1 in NSCLC

2231

Identification of DNA methylation markers to distinguish early-stage lung adenocarcinomas from benign pulmonary nodules

3713

DNA damage response gene alterations and their association with tumor mutation burden and response to immunotherapy in NSCLC and SCLC

3698

Association of KMT2C/D mutations with tumor mutation burden and response to immune checkpoint inhibitors in NSCLC

2007

Molecular Alterations of KIT Oncogene in a Large Cohort of Chinese Pan-Lung Cancer Patients

835

Activating IDH Mutation as Resistance Mechanism to EGFR TKI in EGFR+ NSCLC

1452

A Large-Scale Survey of IDH Mutation in Chinese Patients With NSCLC

Zymeworks Advances HER2 Bispecific Antibody-Drug Conjugate, ZW49, into Expansion Cohort Stage of Clinical Development

On January 27, 2021 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported that the Company has begun enrolling patients into the expansion cohort portion of the ongoing Phase 1 clinical trial for ZW49, its novel HER2-targeted antibody-drug conjugate (ADC) (Press release, Zymeworks, JAN 27, 2021, View Source [SID1234574344]). Supporting data from the Phase 1 dose escalation portion were highlighted today via a webcast and conference call and are summarized below.

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Phase 1 Dose Escalation Study Design

The dose escalation portion of the study employed a standard 3 + 3 design to evaluate escalating doses within different dosing regimens including once every two week (Q2W) and once every three week (Q3W) schedules with the objective of selecting a dose and schedule to advance into the expansion cohorts.

To date patients from sites across the US and Canada with a variety of heavily pretreated HER2‑positive cancer types have been enrolled, including breast cancer, gastroesophageal adenocarcinoma, gynecologic cancers, non-small cell lung cancer, anal cancer, and colorectal cancer.

ZW49 Safety and Tolerability

In the 35 patients who have received ZW49 across all dosing regimens, there have been no dose limiting toxicities, no treatment-related hematologic toxicities including neutropenia or thrombocytopenia, no treatment-related pulmonary toxicity including interstitial lung disease or pneumonitis, and no treatment-related liver toxicity. There have been no treatment-related deaths.

Over 90% of treatment-related adverse events have been mild or moderate (Grade 1 or 2) in severity, with the most common being keratitis, fatigue, and diarrhea, which have been reversible and manageable in an outpatient setting. There have been no discontinuations due to treatment-related adverse events, and the maximum-tolerated dose has not yet been established.

ZW49 Interim Antitumor Activity

ZW49 has demonstrated antitumor activity across all regimens and dose levels evaluated to date, including at the starting dose of 1 mg/kg Q2W. Partial responses and stable disease per RECIST 1.1 have been observed in both Q2W and Q3W dosing regimens, with the Q3W regimen starting to demonstrate a dose-response relationship. Beginning at the initial dose of 2.0 mg/kg Q3W, several patients experienced stable disease including some with disease control greater than four months. At the highest doses tested in the Q3W of 2.5 or 3.0 mg/kg there were six response-evaluable patients with centrally confirmed HER2‑positive disease spanning several different tumor types. The antitumor activity in these six patients consisted of two patients with confirmed partial responses and two patients with stable disease, three of which are still active on study. This regimen is currently enrolling patients at the 3 mg/kg dose with the potential to add new escalation cohorts.

"We are encouraged by the antitumor activity we are seeing so far with ZW49 and look forward to accelerating development by expanding our dataset in disease-specific cohorts," said Diana Hausman, M.D., Chief Medical Officer of Zymeworks. "In addition, the differentiated safety profile allows us to continue in dose escalation, with the opportunity to fully realize the therapeutic potential for ZW49."

Expansion Cohort Phase

Based on the antitumor activity demonstrated by ZW49, three indication-specific expansion cohorts utilizing the 2.5 mg/kg Q3W regimen are open and enrolling patients. These include HER2-positive breast cancer, HER2-positive gastroesophageal adenocarcinoma, and a basket cohort of other HER2-positive cancers. The expansion cohorts are actively enrolling at sites in U.S. and Canada, and are expected to open soon at additional sites in South Korea and Australia in collaboration with our partner, BeiGene.

"I believe ZW49 is on track for becoming the HER2 ADC that delivers efficacy without compromising safety," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "These data highlight that ZW49 can potentially provide physicians and their patients with a differentiated alternative to currently-approved HER2 ADCs. We look forward to presenting additional data at a medical conference later this year."

About ZW49

ZW49, Zymeworks’ second product candidate, is a novel bispecific HER2-targeted ADC developed using Zymeworks’ proprietary Azymetric and ZymeLink platforms. ZW49 combines the unique design of zanidatamab with a proprietary cytotoxin and cleavable linker resulting in enhanced internalization and tumor cell killing. ZW49 is currently in a Phase 1 clinical trial and is being developed for several indications characterized by HER2 expression, especially for patients whose tumors have progressed or are refractory to HER2-targeted agents and those that express lower levels of HER2 and are ineligible for treatment with existing HER2-targeted therapies.

About ZymeLink Antibody-Drug Conjugates

The ZymeLink ADC platform is a modular suite of proprietary cytotoxins (cell-killing drugs), customizable linkers, and conjugation technologies designed for targeted delivery of cytotoxins to diseased cells with optimal safety and efficacy. The ZymeLink platform can be combined with a diverse array of targeted therapies, including traditional antibodies and Azymetric bispecific antibodies, to deliver cell-killing compounds to diseased target cells. These modular technologies are designed to develop next-generation ADCs with broad therapeutic windows.

Cellectar Receives Orphan Drug Designation from the European Commission for CLR 131 in Waldenstrom’s Macroglobulinemia

On January 27, 2021 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development, and commercialization of drugs for the treatment of cancer, reported that the European Medicines Agency has adopted a positive opinion for CLR 131 orphan designation for the treatment of Waldenstrom’s Macroglobulinemia (WM) (Press release, Cellectar Biosciences, JAN 27, 2021, View Source [SID1234574343]).

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European orphan designation is given to medicinal products that are deemed to provide a clinically relevant advantage or make a major contribution to patients’ care, compared with existing methods to treat the condition; are intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating; and where prevalence of the condition in the EU is less than 5 in 10,000 persons.

"WM is an incurable disease with treatment options restricted to one approved drug and various salvage therapies. The 100% overall response rate and durability of these responses after four 15 minute infusions spread over 80 days seen to date with CLR 131, supports our belief that CLR 131 can be an important therapy for WM patients," said James Caruso, president and CEO of Cellectar. "Receipt of European orphan drug designation provides Cellectar with significant regulatory benefits and further validates the clinical potential of CLR 131 in WM. In addition, the European orphan designation complements our U.S. orphan drug and U.S. fast track designations previously granted by the FDA."

Cellectar has initiated a pivotal trial evaluating CLR 131 in Waldenstrom’s macroglobulinemia patients that have failed or had a suboptimal response to a Bruton’s tyrosine kinase inhibitor at select US cancer centers and intends to expand the trial to additional US and international sites in the first quarter of the year. Additional information can be found at www.ClinicalTrials.gov.

The European Medicines Agency (EMA) plays a central role in facilitating the development and authorization of medicines for rare diseases. Orphan designation benefits include protocol assistance, reduced EU regulatory filing fees and 10 years of European market exclusivity which protects CLR 131 from competition from similar medicines with similar indications, which cannot be marketed during the exclusivity period. Designated orphan medicines are also eligible for conditional marketing authorization which is a pragmatic tool for the fast-track approval of a medicine that fulfills an unmet medical need. Detailed information on orphan designation can be found here.

Exelixis to Release Fourth Quarter and Full Year 2020 Financial Results on Wednesday, February 10, 2021

On January 27, 2021 Exelixis, Inc. (Nasdaq: EXEL) reported that its fourth quarter and full year 2020 financial results will be released on Wednesday, February 10, 2021 after the markets close. At 5:00 p.m. EST / 2:00 p.m. PST, Exelixis management will host a conference call and webcast to discuss the results and provide a general business update (Press release, Exelixis, JAN 27, 2021, View Source [SID1234574342]). Access to the event is available via the Internet from the company’s website.

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To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 855-793-2457 (domestic) or 631-485-4921 (international) and provide the conference call passcode 5481036 to join by phone.

A telephone replay will be available until 8:00 p.m. EST on February 12, 2021. Access numbers for the telephone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 5481036. A webcast replay will also be archived on www.exelixis.com for one year.