On June 29, 2022 Scorpion Therapeutics, Inc. ("Scorpion Therapeutics"), a pioneering biotechnology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, reported that it has selected STX-721 as a development candidate from its STX-EGFR-EXON20 program (Press release, Scorpion Therapeutics, JUN 29, 2022, View Source [SID1234616377]). STX-721 is a next-generation, orally delivered small molecule designed with potentially best-in-class selectivity to target Exon 20 insertion mutations in epidermal growth factor receptors ("EGFR"), a well-known, clinically validated oncogenic driver in non-small cell lung cancer ("NSCLC").

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NSCLC is the most common form of lung cancer and EGFR mutations are one of the most common mutations in NSCLC. NSCLC tumors that express EGFR with Exon 20 insertion mutations have an incidence of approximately 3,400 patients per year in the United States. Commercially available therapies for NSCLC patients with EGFR Exon 20 insertion mutations have moderate clinical efficacy and are limited by significant toxicities associated with the inhibition of wild-type EGFR in healthy tissues such as the skin and GI tract. These toxicities can lead to dose reductions or interruptions, which may reduce efficacy and leave a significant unmet need.

"We are delighted to announce STX-721 as our second clinical program," said Axel Hoos, M.D., Ph.D., Chief Executive Officer of Scorpion Therapeutics. "While currently marketed agents have transformed the treatment of many EGFR-mutant lung cancers, patients presenting with Exon 20 insertion mutations remain underserved by existing options, which lack sufficient selectivity over wild-type EGFR and therefore carry significant, dose-limiting toxicities that narrow the therapeutic window and attenuate their efficacy. STX-721 was designed as a next-generation molecule to overcome these limitations. We look forward to sharing the detailed preclinical profile for STX-721 later this year and to submitting an IND to the U.S. Food and Drug Administration in 2023."

Leveraging its proprietary drug-hunting platform, Scorpion Therapeutics designed a highly differentiated candidate molecule that provides exquisitely selective inhibition of Exon 20 insertion mutations compared to the wild-type form of the protein. This may allow for maximal inhibition of the mutant protein in cancer cells compared to normal tissues, thereby reducing the toxicities that lead to dose limitations or reductions with existing EGFR Exon 20 inhibitors. In preclinical studies, STX-721 demonstrated best-in-class selectivity versus all other disclosed clinical-phase Exon 20 inhibitors, as well as dose-dependent anti-tumor activity in xenograft models at well-tolerated doses. Scorpion Therapeutics expects to present these preclinical data at a medical meeting in the second half of 2022 and to submit an IND for STX-721 in 2023.

On June 29, 2022 Harbinger Health, a biotechnology company pioneering the detection of early cancer, and Sarah Cannon Research Institute (SCRI) reported the initiation of a 10,000-participant clinical study designed to validate and further develop Harbinger’s novel platform technology for blood-based early cancer detection (Press release, Sarah Cannon Research Institute, JUN 29, 2022, View Source [SID1234616376]).

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The Cancer ORigin Epigenetics- Harbinger Health (CORE-HH) study plans to enroll a diverse and representative population with and without cancer at up to 40 sites across the U.S. The study is being run by SCRI’s contract research organization and has begun enrollment at sites affiliated with HCA Healthcare, SCRI’s parent company.

The primary objectives of the case-control study are to further develop and validate the diagnostic accuracy of Harbinger’s platform technology for the detection of early-stage cancer across multiple cancer types and to assess the ability to determine tumor location. The study, which is expected to read out in stages through 2023, is designed to advance Harbinger’s product development strategy.

"We are pleased to work with SCRI, a leading clinical research organization conducting community-based clinical trials, as we drive toward Harbinger’s goal of enabling the detection of cancer at the earliest points of disease, well before current means of screening could find it and when it’s possible to intervene with the greatest possibilities of success," said Stephen Hahn, MD, CEO of Harbinger Health. "We share a vision of a world where nearly all cancers can be identified before they are symptomatic or even visible with simple, highly accurate and reliable blood tests that are widely accessible, particularly to those who have traditionally been underserved in our healthcare system."

"Improving the ability to detect more cancers at earlier stages is important," said Howard A. "Skip" Burris III, MD, FACP, FACSO, President & Chief Medical Officer, SCRI. "Blood-based testing has emerged in recent years as a potential way to address this important need, and we are excited to partner with Harbinger Health to develop testing capabilities that should improve outcomes for cancer patients through earlier diagnosis."

On June 29, 2022 Avacta Group plc (AIM: AVCT), a clinical stage oncology drug company and developer of powerful diagnostics based on its innovative Affimer and pre|CISION platforms, reported that the first-in-human Phase I trial (ALS-6000-101) of AVA6000 Pro-doxorubicin will advance to the third dose cohort following a positive review of the safety data from the dosing of the second cohort (Press release, Avacta, JUN 29, 2022, View Source [SID1234616375]).

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Avacta’s Safety Data Monitoring Committee (SDMC), comprised of clinicians currently recruiting patients, has completed its review of the safety data from the second cohort dosed with AVA6000 at 120mg/m2 in the ongoing Phase I trial. Following this review, the SDMC has recommended that the clinical trial continues as planned and escalates to the next dose of AVA6000 at 160mg/m2.

AVA6000 is a novel form of doxorubicin that has been modified with Avacta’s pre|CISION FAP-activated delivery platform to improve its safety and therapeutic index. AVA6000 has been designed to limit cell penetration of the drug, and therefore its cell killing effect, until it is specifically activated by fibroblast activation protein α (FAP) which is in high concentration in many solid tumours compared with healthy tissues. The resulting reduced exposure of healthy tissues to active doxorubicin has the potential to significantly increase its therapeutic index by reducing the incidence of adverse effects, including cardiotoxicity and myelosuppression. Anthracyclines such as doxorubicin, a generic chemotherapeutic agent, with a market size that is expected to grow to $1.38bn by 20241, are widely used as part of standard of care in several tumour types, but doxorubicin’s use is limited by cumulative toxicity associated with cardiomyopathy.

Dr Alastair Smith, Chief Executive Officer of Avacta, commented: "AVA6000, and the pre|CISION platform more broadly, have the potential to deliver safer and affordable oncology drugs that could significantly improve cancer patients’ lives. We are very pleased with the progress being made with ALS-6000-101 study and look forward to seeing more data as it emerges from the trial."

Neil Bell, Chief Development Officer of Avacta, commented: "The recommendation from the Safety Data Monitoring Committee to initiate dosing in Cohort 3 with 160mg/m2 of AVA6000 is an endorsement of the emerging safety and tolerability profile in the patients enrolled in this study to date. We look forward to providing additional updates as the dose escalation phase of the trial progresses."

On June 29, 2022 Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of therapeutics designed to activate the immune response to cancers and infections, reported expanded data from the Phase 1b study of botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) in patients with microsatellite stable colorectal cancer (MSS CRC) (Press release, Agenus, JUN 29, 2022, View Source [SID1234616374]). The data demonstrate that the combination offers strong durability and superior efficacy than what has been reported in separate trials for standard of care and other investigational therapies in 2L+ MSS CRC.

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"These data reinforce the strong therapeutic potential of botensilimab, when used in combination with balstilimab, in cold tumors such as MSS CRC," said Steven O’Day, MD, Chief Medical Officer at Agenus. "Thus far, botensilimab has demonstrated activity in nine cold and treatment-resistant cancers, and we plan to initiate a robust, global Phase 2 program, including in MSS CRC, later this year."

Study Highlights

A total of 41 evaluable patients with metastatic MSS CRC received either 1 or 2 mg/kg botensilimab Q6W, and 3 mg/kg balstilimab Q2W. Patients were heavily pre-treated, with a median of 4 prior lines of therapy, and 34% had received prior immunotherapy. The botensilimab/balstilimab combination produced superior responses and strong durability, relative to what has been reported in separate trials for standard of care and other combinations currently in development.

Objective responses:

24% overall response rate
73% disease control rate (partial response + stable disease)
50% objective responses with greater than 50% tumor reduction
Durability:

80% objective responses ongoing at data cut-off
30% objective responses exceeding 1 year
Patient Sub-Populations:

Objective responses in 5 patients with RAS mutations for a 24% overall response rate and 81% disease control rate in this population; other PD-1 combinations in separate trials have reported only rare responses in this population (≤1% response rate)
Responses observed in patients with metastases historically resistant to immunotherapy, including patients with malignant pleural effusions, soft tissue, peritoneal, retroperitoneal, and bone metastases
Tolerability:

Botensilimab was well tolerated, with no grade 4/5 treatment-related adverse events
Rates of gastrointestinal and skin toxicities were comparable to those reported with first-generation CTLA-4 inhibitors
"Colorectal cancer is the second leading cause of cancer-related death worldwide, with roughly 95% classified as microsatellite stable and historically unresponsive to immunotherapy. Treatment resistant MSS CRC patients lack effective options, with standard of care offering only a 1-2% response rate and a median expected survival ranging from 6 to 7 months," said Anthony El-Khoueiry, MD, Phase I Program Director at the USC Norris Comprehensive Cancer Center, Keck Medicine of USC. "The combination of robust response rate, durability, and tolerability demonstrated by botensilimab and balstilimab supports further development of the combination in MSS CRC, as well as more broadly, in other cold and treatment-resistant tumors."

Presentation Details

The data were presented today at 7:05 AM EDT in a late-breaking oral presentation at the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Abstract Title: Botensilimab, a Novel Innate/Adaptive Immune Activator, Plus Balstilimab (Anti-PD-1) for Metastatic Heavily Pretreated Microsatellite Stable Colorectal Cancer

Abstract Number: LBA-09

Presenting Author: Dr. Anthony El-Khoueiry, M.D., Associate Director of Clinical Research at the USC Norris Comprehensive Cancer Center, Keck School of Medicine

Investor Webcast

The Company will host an investor webcast today at 10:00 AM EDT to review these data. Participants may register here, or on the Investors section of the Agenus website at investor.agenusbio.com. The webcast will include presentations by the below speakers and will be followed by a Q&A session:

Steven O’Day, M.D., Agenus’ Chief Medical Officer
Dr. Anthony El-Khoueiry, M.D., Associate Director of Clinical Research at the USC Norris Comprehensive Cancer Center, Keck School of Medicine
Dr. Manuel Hidalgo, Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine/NewYork-Presbyterian Hospital, and
Dr. Heinz-Josef Lenz, M.D., Professor of Medicine and J. Terrence Lanni Chair in Gastrointestinal Cancer Research, Keck School of Medicine
Following the webcast, an archived version will be available on the Agenus website.

On June 29, 2022 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that it will hold its second-quarter 2022 sales and earnings conference call with institutional investors and analysts at 8:00 a.m. ET on Thursday, July 28 (Press release, Merck & Co, JUN 29, 2022, View Source [SID1234616373]). During the call, company executives will provide an overview of Merck’s performance for the quarter and outlook.

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Investors, journalists and the general public may access a live audio webcast of the call via this weblink. A replay of the webcast, along with the sales and earnings news release, supplemental financial disclosures, and slides highlighting the results, will be available at www.merck.com.

Participants may join the call by dialing 877-692-8955 (USA Toll-Free) or 234-720-6979. If you are calling from other countries, visit this weblink. All dial-in participants can use the access code 1857604. Journalists who wish to ask questions are requested to contact a member of Merck’s Media Relations team.