On November 1, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that its license partner, China Oncology Focus Limited (COF), an affiliate of Lee’s Pharmaceutical Holdings Limited (Lee’s Pharma, HKEX: 950) has submitted a NDA (new drug application) for the anti-PD-L1 antibody, socazolimab, licensed from Sorrento to COF for the greater China territory to treat recurrent or metastatic cervical cancer (Press release, Sorrento Therapeutics, NOV 1, 2021, View Source [SID1234594001]). The NDA application has been accepted by China NMPA.

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 February 2021, Sorrento and Lee’s Pharma announced that socazolimab had been granted breakthrough designation by the NMPA. If approved by NMPA, this will be the first approved fully human antibody discovered and isolated from Sorrento’s proprietary G-MAB library. "This is a major step forward that demonstrates the power of discovery and development engines at Sorrento for producing proprietary biopharmaceuticals for unmet medical needs," said Dr. Henry Ji, Chairman and CEO of Sorrento.

About Socazolimab

Socazolimab is a fully human anti-PD-L1 monoclonal antibody identified by Sorrento using its proprietary G-MAB library platform. COF received exclusive rights to develop and commercialize the antibody for Greater China, which includes Mainland China, Hong Kong, Macau, and Taiwan. Socazolimab has the following potential advantages over its competitors:

Fully human antibody potentially allows it to have minimal immunogenicity; demonstrated by its negative antigen-derived antibody (ADA) generation in humans in studies to date.
Potentially lower dose required to achieve efficacy compared to other anti-PD-L1 antibodies.
Dual mechanism of action observed with both immune-checkpoint inhibition and antibody-dependent cellular cytotoxicity (ADCC) effect.
The antibody has been tested or is being tested in various cancer indications including recurrent or metastatic cervical cancer, maintenance therapy for high-grade osteosarcoma after adjuvant chemotherapy, locally advanced and metastatic urothelial carcinoma, extensive small cell lung cancer in combination with carboplatin and etoposide, advanced urothelial carcinoma in combination with albumin-bound paclitaxel and esophageal carcinoma.

On November 1, 2021 Curaleaf International (the "Company") (formerly EMMAC Life Sciences Group), part of Curaleaf Holdings (CNSX:CURA), Europe’s largest vertically integrated cannabis company, reported its official rebrand to the European market (Press release, EMMAC Life Sciences, NOV 1, 2021, View Source [SID1234593994]). It has been three years to the day since the UK Government’s landmark decision to legalise cannabis-based products for medicinal use, paving the way for further significant developments to the cannabis sector. In this time Curaleaf International has experienced exponential growth in cannabis revenues, as the demand for premium medicinal cannabis continues to grow.

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!

Curaleaf International’s cannabis flower products and extracted cannabis-based products now supply five separate markets, including Germany, Europe’s largest market for medicinal cannabis which is expected to be worth over €840 million by 20251. In the UK, specifically over the last 12 months, the number of patients using the Company’s products have increased fivefold.

Building on the momentum within the European medicinal cannabis market, Curaleaf International expects to see significant regulatory change across Europe for adult use (recreational) cannabis over the coming years with expectations that the total European cannabis market will be worth €3.2 billion by 20251. Curaleaf International expects the trends to follow that of Canada and the USA, which both started with the legalisation of medicinal cannabis before moving to legalise cannabis for adult use. With a population of approximately 740 million people, Europe presents a greater market size than that of North America.

The potential commercial impact of cannabis legalisation in Europe is significant. One in 10 Europeans use cannabis every year, while a quarter of people admit to having used cannabis at least once in their lifetime. The annual sales in illicit market cannabis are estimated at around €11 billion1. As highlighted in The European Cannabis Report: 6th Edition1, it is projected that sales of adult-use cannabis will reach €200 million by 2023, coming close to €800 million in 2025. Taking into account growth in the recreational sector due to decreasing stigma and ease of access, Prohibition Partners increased their total market estimate from €800 million to €3.2 billion by 20251.

The Company expects that over the next three to four years significant regulatory changes will occur across the continent. Recent progress has notably occurred in Switzerland, the Netherlands, Italy and Germany. Since May 2021, Switzerland allows the sale of adult use cannabis under a trial basis. In Zurich, the country’s largest city, consumers will be allowed to buy cannabis products from pharmacies and social clubs.3 In the Netherlands, 10 licences have been issued for a recreational cannabis pilot project to supply 79 "coffee shops" in 10 municipalities. In Germany, the largest market in Europe for medical cannabis, the likely new coalition Government under the SPD, Greens and FDP parties are all in favour of legalising adult use cannabis. Additionally, Italy could be the first European nation to make adult use cannabis legal. The country is due to have a referendum proposing the legalisation of adult use cannabis in 2022, with an expected result of 57% voting in favour of legalising4, the potentially €8 billion market presents a lucrative opportunity for first movers such as Curaleaf International.

With the anticipated regulatory changes across Europe, Curaleaf International believes this is a pivotal moment for the European cannabis industry. The Company is uniquely positioned within Europe with a fully vertically integrated model, handling every aspect of the process from seed to shelf. The Company has two operating EU-GMP processing facilities and import and distribution capabilities in place in the UK and Germany.

Commenting on the European opportunity, Antonio Costanzo, CEO of Curaleaf International, said: "We have seen good growth in medicinal cannabis across Europe, and building on this momentum, the official launch of Curaleaf International has been designed to create a European cannabis platform to capitalise on the rapidly emerging opportunities that are accelerating in line with regulatory change and cultural acceptance. The landscape in Europe is changing and we can see similar clear patterns to the progress in North America for adult use cannabis. As the only established fully integrated cannabis company in Europe, our first mover advantage gives us complete control over the supply chain, and this, coupled with our science led approach leaves Curaleaf International best positioned to capitalise on this potentially enormous market."

On November 1, 2021 United Therapeutics Corporation (Nasdaq: UTHR) reported that Michael Benkowitz, President and Chief Operating Officer of United Therapeutics, will provide an overview and update on the company’s business during a fireside chat session at the Credit Suisse 30th Annual Healthcare Conference (Press release, United Therapeutics, NOV 1, 2021, View Source [SID1234593988]).

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 session will take place virtually on Monday, November 8, 2021, from 8:50 a.m. to 9:30 a.m., Eastern Standard Time, and can be accessed via a live webcast on the United Therapeutics website at View Source An archived, recorded version of the session will be available approximately 24 hours after the session ends and can be accessed at the same location for 90 days.

On November 1, 2021 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported a collaboration with Guardant Health, a leading precision oncology company, focused on characterizing the prevalence of patients with advanced solid tumors bearing BRAF Class I, II and III alterations (Press release, Kinnate Biopharma, NOV 1, 2021, View Source [SID1234593987]). The study will also assess real-world clinical outcomes stratified by BRAF alteration class and by treatment type.

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!

"Currently, patients with Class II and III BRAF alterations have no available targeted therapies and represent a significant and potentially greater unmet clinical need than previously understood," said Richard Williams, MBBS, Ph.D., Chief Medical Officer at Kinnate. "With a focus on metastatic disease and longitudinal genomics data, GuardantINFORM has provided valuable insights into this important biomarker that will help us to guide the development of our lead BRAF candidate. We believe that this collaboration with Guardant Health will enable a deeper look at the occurrence rates of functionally distinct classes of BRAF alterations across patient groups and help advance our efforts to develop novel targeted therapies that improve their lives."

Preliminary analyses conducted utilizing the GuardantINFORM platform suggest that the prevalence of Class II and III alterations across patients with advanced and metastatic solid tumors screened via liquid biopsy-based comprehensive genomic profiling (CGP) is higher than previously understood. Among the nearly 6,000 patients who were identified as having BRAF alteration-positive cancers, approximately 55% were found to be harboring Class II and III alterations across all tumor types. When looking across common tumor types – Non-Small Cell Lung Cancer (NSCLC), Melanoma and Colorectal Cancer (CRC) – approximately 65%, 20% and 30% of oncogenic BRAF alterations, respectively, are BRAF Class II and III. In addition to NSCLC, Melanoma, and CRC, BRAF Class II and III alterations are also detected at substantial rates in other common and rare tumor types such as prostate, breast, duodenal adenocarcinoma, renal pelvis urothelial carcinoma, and cholangiocarcinoma. These findings, as well as other studies that will assess real-world clinical outcomes stratified by BRAF Class and by treatment, are planned for presentation at a future date.

"Analysis of large-scale, real-world clinical-genomic datasets has become a critical approach for our biopharmaceutical partners like Kinnate to gain unique insights into disease biology, prevalence, and clinical outcomes across diverse patient populations," said Daniel Simon, Senior Vice President of Biopharma Solutions at Guardant Health. "Through GuardantINFORM, we can provide our partners like Kinnate with a unique perspective into biomarkers such as BRAF that drive tumors for patient populations where there is greatest unmet need."

Kinnate is utilizing the GuardantINFORM platform which combines de-identified longitudinal clinical information and genomic data collected from the Guardant360 liquid biopsy test which has been provided to more than 175,000 patients to date in the United States. Its robust dataset offers real-world insights into anti-cancer therapy use in the clinic, tumor evolution, and treatment resistance throughout each patient’s treatment journey for many advanced solid tumor cancers including NSCLC, Melanoma, Breast, CRC and Prostrate.

On November 1, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) and AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq: AZN) reported that they have initiated SAMETA, a global Phase III study of savolitinib (ORPATHYS in China), an oral, potent, and highly selective small molecule inhibitor of MET, a receptor tyrosine kinase, in combination with AstraZeneca’s PD-L1 inhibitor IMFINZI (durvalumab) in patients with MET-driven advanced papillary renal cell carcinoma ("PRCC") (Press release, Hutchison China MediTech, NOV 1, 2021, View Source [SID1234593986]). The first patient received their first dose on October 28, 2021.

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 III trial is an open-label, randomized, controlled study in treatment-naïve patients with MET-driven, unresectable and locally advanced or metastatic PRCC, to evaluate the efficacy and safety of savolitinib in combination with IMFINZI, compared to single agent IMFINZI or single agent SUTENT (sunitinib), an oral multi-kinase inhibitor considered the standard-of-care treatment option in PRCC. The primary endpoint of the study is median progression free survival ("PFS"). Other endpoints include median overall survival ("OS"), objective response rate ("ORR"), duration of response ("DoR"), 6-months and 12-months disease control rate ("DCR"), time to second progression (PFS2), safety, pharmacokinetics ("PK") and quality of life. Additional details may be found at clinicaltrials.gov, using identifier NCT05043090.

About PRCC
PRCC is a subtype of kidney cancer that is unusually difficult to treat, with low response rates from current treatment options and no treatments approved for patients with tumors that harbor MET-driven alterations. Worldwide, about 430,000 new patients were diagnosed with kidney cancer in 2020[1]. In the US, an estimated 76,000 people will be diagnosed with kidney cancer in 2021[2]. Approximately 90% of kidney tumors are renal cell carcinoma ("RCC"), which consist of several heterogeneous subtypes with highly variable clinical courses and outcomes[3],[4]. PRCC accounts for up to 15% of RCC[4],[5]. The MET gene has been found to be a major chromosome-level alteration in 81% of type-1 PRCC and 46% of type-2 PRCC, or 63% of PRCC[6].

About Savolitinib (ORPATHYS in China)
Savolitinib 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.

Savolitinib is marketed in China under the brand name ORPATHYS 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 savolitinib. 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 savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.

Savolitinib development in NSCLC
Phase II study of savolitinib monotherapy in MET Exon 14 skipping alteration NSCLC (NCT02897479) – In June 2021, savolitinib 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 published in The Lancet Respiratory Medicine[7]. At a median follow up of 17.6 months, savolitinib demonstrated an ORR of 42.9% (95% confidence interval [CI] 31.1-55.3) and median PFS of 6.8 months (95% CI 4.2-9.6) in the overall trial population. DCR in the overall trial population was 82.9% (95% CI 72.0-90.8). The safety and tolerability profile of savolitinib 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).

TATTON Phase Ib/II expansion studies of savolitinib in combination with TAGRISSO in patients who have progressed following EGFR TKI treatment due to MET amplification (NCT02143466) – This global exploratory study in over 220 EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI. Results were published in Lancet Oncology[8] and final analysis was presented at the World Conference on Lung Cancer[9]. Three cohorts with patients treated following progression on first- or second-generation EGFR TKI demonstrated an ORR of 64.7-66.7% and a median PFS of 9.0-11.1 months. The cohort of patients treated following progression on a third-generation EGFR TKI demonstrated an ORR of 33.3% (95% CI 22.4-45.7), with a median PFS of 5.5 months (95% CI 4.1-7.7). The combination demonstrated encouraging anti-tumor activity and an acceptable risk-benefit profile.

SAVANNAH Phase II study of savolitinib 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.

SACHI Phase III study of savolitinib in combination with TAGRISSO in patients who have progressed following EGFR TKI treatment due to MET amplification (NCT05015608) – 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.

SANOVO Phase III study of savolitinib in combination with TAGRISSO in treatment-naïve patients with EGFR mutant positive NSCLC with MET overexpression (NCT05009836) – This is a randomized, blinded study in China in untreated, unresectable or metastatic patients with EGFR mutation positive NSCLC with MET positive tumors.

Savolitinib development in kidney cancer
SAVOIR randomized, controlled study of savolitinib monotherapy in MET-driven PRCC (NCT03091192) – In May 2020, data from 60 patients in this global study of savolitinib 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[10]. Savolitinib demonstrated encouraging activity, including an ORR of 27% versus 7% for sunitinib, with no savolitinib responding patients experiencing disease progression at data cut-off, and an encouraging 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 savolitinib in combination with IMFINZI PD-L1 inhibitor in RCC (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of savolitinib in combination with IMFINZI, a PD-L1 antibody owned by AstraZeneca. The study is evaluating the safety and efficacy of the savolitinib/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[11], showing a confirmed response rate in 8 out of the 14 MET-driven patients, or 57%, with a median DoR of 9.4 months, median PFS of 10.5 months and median OS of 27.4 months. No new safety signals were seen.

SAMETA Phase III study in combination with IMFINZI PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic PRCC (NCT05043090) – Based on the encouraging results of the SAVOIR and CALYPSO studies, we have initiated SAMETA, a global Phase III, open-label, randomized, controlled study of savolitinib plus IMFINZI versus sunitinib monotherapy versus IMFINZI monotherapy in patients with MET-driven, unresectable and locally advanced or metastatic papillary RCC.

Savolitinib development in gastric cancer
Phase II study of savolitinib monotherapy in advanced or metastatic MET amplified gastric cancer ("GC") or adenocarcinoma of the gastroesophageal junction ("GEJ") (NCT04923932) – This is an open-label, two-cohort, multi-center study to evaluate the efficacy, safety and PK of savolitinib in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy.

This trial follows multiple Phase II studies that have been conducted in Asia to study savolitinib in MET-driven GC patients, including VIKTORY[12]. VIKTORY is an investigator initiated Phase II umbrella study in GC in South Korea in which a total of 715 patients were successfully sequenced into molecular-driven patient groups, including those with MET amplified GC. Patients whose tumors harbor MET amplification were treated with savolitinib monotherapy, reporting an ORR of 50% (10/20, 95% CI: 28.0, 71.9).

Savolitinib development in other cancer indications
Savolitinib opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including colorectal cancer.

About IMFINZI
IMFINZI (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

IMFINZI is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy and is the global standard of care in this setting based on the PACIFIC Phase III trial.

IMFINZI is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer ("SCLC") based on the CASPIAN Phase III trial.

IMFINZI is also approved for previously treated patients with advanced bladder cancer in several countries. Since the first approval in May 2017, more than 100,000 patients have been treated with IMFINZI.

As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, SCLC, bladder cancer, liver cancer, biliary tract cancer, esophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumors.