On July 28, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) and AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq: AZN) reported that they have initiated a Phase II study of ORPATHYS (savolitinib), an oral, potent, and highly selective small molecule inhibitor of MET, a receptor tyrosine kinase, in patients with advanced or metastatic MET amplified gastric cancer ("GC") or adenocarcinoma of the gastroesophageal junction ("GEJ"). The first patient was dosed on July 27, 2021 (Press release, Hutchison China MediTech, JUL 28, 2021, View Source [SID1234586918]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase II trial is an open-label, two-cohort, multi-center study to evaluate the efficacy, safety and pharmacokinetics ("PK") of ORPATHYS in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy. The primary endpoint is objective response rate ("ORR") as assessed by an independent review committee. Other endpoints include 12-week and 6-month progression-free survival ("PFS") rates, median PFS, duration of response ("DoR"), disease control rate ("DCR"), median overall survival ("OS"), safety, PK and quality of life.

The Beijing Cancer Hospital is the lead institution of this study. The lead investigator is Dr Shen Lin. For more information, please see clinicaltrials.gov identifier: NCT04923932.

MET-driven gastric cancer has a very poor prognosis.[i] This trial follows multiple Phase II studies that have been conducted in Asia to study ORPATHYS in MET-driven gastric cancer patients, including VIKTORY.2 VIKTORY is an investigator initiated Phase II umbrella study in gastric cancer in South Korea in which a total of 715 patients were successfully sequenced into molecular-driven patient groups, including those with MET amplified gastric cancer. Patients whose tumors harbor MET amplification were treated with ORPATHYS monotherapy, reporting an ORR of 50% (10/20, 95% CI: 28.0, 71.9).

It is estimated that MET amplification accounts for approximately 4-6% of GC patients.[ii],[iii] The annual incidence of MET amplification GC is estimated to be approximately 24,000 in China.[iv]

About ORPATHYS
ORPATHYS is an oral, potent, and highly selective MET tyrosine kinase inhibitor ("TKI") that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

ORPATHYS is marketed in China for the treatment of patients with non-small cell lung cancer ("NSCLC") with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

In 2011, following its discovery and initial development by HUTCHMED, AstraZeneca and HUTCHMED entered a global licensing agreement to jointly develop and commercialize ORPATHYS. Joint development in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of ORPATHYS in China. AstraZeneca is responsible for the commercialization of ORPATHYS in China and worldwide. Sales of ORPATHYS will be recognized by AstraZeneca.

ORPATHYS development in NSCLC
Phase II study of ORPATHYS monotherapy in MET Exon 14 skipping alteration NSCLC (NCT02897479) – In June 2021, ORPATHYS was granted drug registration conditional approval by the National Medical Products Administration of China (NMPA) for MET Exon 14 skipping alteration NSCLC. The approval was based on the results of a Phase II study in China; results of this study were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program in May 2020, and updated results were published in The Lancet Respiratory Medicine[v] in June 2021. At a median follow up of 17.6 months, ORPATHYS demonstrated an objective response rate ("ORR") of 42.9% (95% confidence interval [CI] 31.1-55.3) and median progression-free survival ("PFS") of 6.8 months (95% CI 4.2-9.6) in the overall trial population. PFS was clinically meaningful across subgroups, and ORR results were consistent regardless of prior treatment or tumor histology, including in patients with the pulmonary sarcomatoid carcinoma (PSC) subtype (40.0%, 95% CI 21.1-61.3) and patients with other NSCLC subtypes (44.4%, 95% CI 29.6-60.0). Disease control rate ("DCR") in the overall trial population was 82.9% (95% CI 72.0-90.8). The safety and tolerability profile of ORPATHYS was consistent with previous trials, and no new safety signals were identified. Continued approval is contingent upon the successful completion of a confirmatory trial in this patient population (NCT04923945).

SAVANNAH Phase II study of ORPATHYS in combination with TAGRISSO in patients who have progressed following TAGRISSO due to MET amplification or overexpression (NCT03778229) – This is a single-arm, open-label, global study in epidermal growth factor receptor ("EGFR") mutation positive NSCLC patients with MET amplified/overexpressed tumors following progression after treatment with TAGRISSO, an EGFR TKI owned by AstraZeneca.

Phase III study of ORPATHYS in combination with TAGRISSO in patients who have progressed following EGFR TKI treatment due to MET amplification (in planning) – This is a randomized, open-label study in China in EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.

Phase III study of ORPATHYS in combination with TAGRISSO in treatment naïve patients with EGFR mutant positive NSCLC with MET overexpression (in planning) – This is a randomized, blinded study in China in untreated, unresectable or metastatic patients with EGFR mutation positive NSCLC with MET positive tumors.

ORPATHYS development in kidney cancer
SAVOIR randomized, controlled study of ORPATHYS monotherapy in MET-driven papillary renal cell carcinoma ("RCC") (NCT03091192) – In May 2020, data from 60 patients in this global study of ORPATHYS monotherapy compared with sunitinib monotherapy in MET-driven papillary RCC was presented at the ASCO (Free ASCO Whitepaper) 2020 Program and published simultaneously in JAMA Oncology[vi]. ORPATHYS demonstrated encouraging activity, including an ORR of 27% versus 7% for sunitinib, with no ORPATHYS responding patients experiencing disease progression at data cut-off, and an encouraging overall survival ("OS") hazard ratio of 0.51 (95% CI: 0.21–1.17; p=0.110) with median not reached at data cut-off.

CALYPSO Phase I/II study of ORPATHYS in combination with IMFINZI PD-L1 inhibitor in RCC (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of ORPATHYS in combination with IMFINZI, a PD-L1 antibody owned by AstraZeneca. The study is evaluating the safety and efficacy of the ORPATHYS/IMFINZI combination in patients with papillary RCC and clear cell RCC. An analysis of 41 patients enrolled in the PRCC cohort of in this study was presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting[vii], showing a confirmed response rate in 14 MET-driven patients of 57%, with a median duration of response ("DoR") of 9.4 months, median PFS of 10.5 months and median OS of 27.4 months. No new safety signals were seen.

Phase III study in combination with IMFINZI PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic PRCC (in planning) – Based on the encouraging results of the SAVOIR and CALYPSO studies, we intend to initiate a global Phase III, open-label, randomized, controlled study of ORPATHYS plus IMFINZI versus sunitinib monotherapy versus IMFINZI monotherapy in patients with MET-driven, unresectable and locally advanced or metastatic PRCC.

ORPATHYS development in other cancer indications
ORPATHYS opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including non-small cell lung cancer, gastric cancer and colorectal cancer.

On July 28, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that a conference call will be held on Monday, August 2, 2021 at 8:30 AM ET to discuss results for the second quarter 2021 and provide a business outlook for the remainder of the year (Press release, TG Therapeutics, JUL 28, 2021, https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-host-conference-call-second-quarter-2021 [SID1234585262]). Michael S. Weiss, Chairman and Chief Executive Officer, will host the call.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at www.tgtherapeutics.com. An audio recording of the conference call will also be available for a period of 30 days after the call.

TG Therapeutics will announce its financial results for this period in a press release to be issued prior to the call.

On July 28, 2021 GlaxoSmithKline reported that Sales growth driven by strong commercial execution and favourable prior year comparison (Press release, GlaxoSmithKline, JUL 28, 2021, View Source [SID1234585283])

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pharmaceuticals £4.2 billion +3% AER, +12% CER with growth in New and Specialty products (+25% CER) including Respiratory +36% CER, Immuno-Inflammation +46% CER, Oncology +69% CER, total HIV +14% CER

Vaccines £1.6 billion +39% AER, +49% CER reflecting strong growth in Meningitis +46% CER, Established Vaccines
+28% CER, Shingrix +1% CER with improved performance notably in the US and £258 million pandemic adjuvant sales. Continue to expect strong growth from Shingrix in H2

Consumer Healthcare £2.3 billion -4% AER, +3% CER (+7% CER excluding divestments/brands under review)

Effective cost control supports delivery of adjusted earnings per share growth
Total Group operating margin 20.7%. Total EPS 27.9p -39% AER, -28% CER
Adjusted Group operating margin 26.7%. Adjusted EPS 28.1p +46% AER, +71% CER (H1 -10% AER, +2% CER). This included a contribution to growth from COVID-19 solutions of approximately +20% AER, +21% CER in Q2 (+7% AER, +7% CER in H1)
Q2 net cash flow from operations £1.3 billion. Free cash flow £316 million

Continued R&D delivery and strengthening of pipeline
FDA rolling review of cabotegravir for prevention of HIV (PrEP) completed
Positive phase III headline results for daprodustat, potential transformative medicine for anaemia due to chronic kidney disease
3 new strategic collaborations announced, iTeos, Alector* and Halozyme strengthen pipeline in next generation immuno-oncology, immuno-neurology and HIV
Emergency use authorisations for sotrovimab; Phase III started for Sanofi-GSK adjuvanted COVID-19 vaccine and EMA rolling review initiated

Investor Update in June outlined new outlooks for growth and plans to maximise shareholder value
GSK expects to deliver step-change in sales, operating profit growth and performance from 2022, driven by high quality Vaccines and Specialty Medicines portfolio and late-stage pipeline
Proposed demerger to create new world-leading Consumer Healthcare company confirmed for mid-2022
Confident in delivering 2021 EPS guidance and reconfirm 2022 outlook
2021 Adjusted EPS to decline by mid-to-high single-digit percentage at CER
2022 meaningful improvements expected in revenues and margins
2021 guidance and 2022 outlook exclude any contribution from COVID-19 solutions
Dividend of 19p/share declared for Q2 2021. Continue to expect 80p/share for 2021

Emma Walmsley, Chief Executive Officer, GSK said:
"GSK delivered an excellent performance in Q2. We expect this positive momentum to continue through the second half of the year driving us towards the better end of our earnings guidance range for 2021, and meaningful performance improvement in 2022. We continue to strengthen our pipeline and are advancing well towards separation. Our clear priority is to focus on execution, unlocking the value of Consumer Healthcare and delivering the step-change in growth and performance we now see for GSK."

On July 28, 2021 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, reported that it will host a conference call and live webcast on Tuesday, August 3, 2021 at 8:30 a.m. EDT to report financial results for the second quarter 2021 and provide business updates (Press release, ADC Therapeutics, JUL 28, 2021, View Source [SID1234585317]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To access the live call, please dial 833-303-1198 (domestic) or +1 914-987-7415 (international) and provide confirmation number 6962756. A live webcast of the presentation will be available under "Events and Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.

On July 28, 2021 Natera,Inc. (NASDAQ: NTRA), a pioneer and global leader in cell-free DNA testing, reported a new peer-reviewed paper published in Gastroenterology validating its personalized and tumor-informed molecular residual disease (MRD) assay, Signatera, in resected esophageal adenocarcinoma (EAC) (Press release, Natera, JUL 28, 2021, View Source [SID1234585334]). The paper can be found here.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study represents the first published data on the use of Signatera in EAC and demonstrates the potential of the Signatera technology in esophageal cancer, which sees around 20,000 new cases per year in the U.S.1

Key findings from this retrospective study of 20 EAC patients after resection:

Signatera detected recurrence with a sensitivity of 80% (4/5). The only missed recurrence had the last sample drawn two years before recurrence. The specificity was 100% (12/12) and the PPV was 100%.
Signatera detected recurrence with a median lead time of almost one year before clinical or radiological recurrence.
Postsurgical MRD-positive patients had disease-free survival of 14.2 months, compared to 51.2 months in MRD-negative patients, indicating prognostic value in this setting.
Patients who were MRD-positive preoperatively and became MRD-negative after surgery had a good prognosis, indicating that Signatera can potentially be used to risk-stratify patients for adjuvant therapy.
"The incidence of esophageal cancer is on the rise globally and more than half of these patients experience recurrence after surgery or treatment with curative intent,"2,3 said Alexey Aleshin, M.D., M.B.A., vice president of medical affairs, oncology at Natera. "For these patients, a sensitive prognostic biomarker, such as Signatera status, could have significant clinical utility in predicting relapse and guiding adjuvant treatment decisions."

This study comes on the heels of another peer-reviewed study recently published in JCO Precision Oncology validating Signatera in oligometastatic cancer, adding to the growing body of evidence behind Signatera in gastrointestinal cancers. To date, Signatera has been published in 14 peer-reviewed publications, in a wide range of cancer types, including colorectal, breast, lung, bladder, pancreatic and more.

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes Signatera’s accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Signatera is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier and to help optimize treatment decisions.

Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Signatera has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.